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- Preparatory Year Students’ Perception of Pharmacy Profession as a
Career Choice
Authors: Fowad Khurshid, Fahad Alharbi, Abdulrahman Almohydib, Shatha Ibn Malik, Hussain A. Al-Omar, Mohammed S. Alsultan, Abdlatif Alghaiheb
Abstract: The study attempted to assess preparatory year students’ perception towards pharmacists and the pharmacy profession. This cross-sectional survey was conducted between December 2019 and March 2020. The students were invited to complete an anonymous questionnaire via Google Forms®. In total, 244 students, of which 53.7% were female with the mean age of 19.2 ± 0.65, from 12 universities participated in this study. As per our findings, the majority of the respondents (91.8%) regard pharmacy as a well-respected profession, 82.4% thought pharmacists are important decision-makers, 68.4% disagreed that most pharmacists were unkind, and 60.7% did not agree that pharmacy was a low-status occupation. Meanwhile, 95.5% agreed that pharmacists must have a university degree, 88.6% agreed pharmacists must take responsibility for patients, and 82.8% believed pharmacists had to work too hard. Moreover, 62.3% did not think pharmacy was a low-skill occupation, 54.9% did not agree pharmacists must do unpleasant things, and 45.1% disagreed pharmacists only did what physicians requested of them. Lastly, 48.8% had low confidence in choosing pharmacy as a career. The students’ overall perception toward pharmacists and the pharmacy profession was favorable. However, only one-fourth of the students displayed a tendency to choose pharmacy as a future career.
PubDate: 2023-07-12
DOI: 10.1590/s2175-97902023e21476
Issue No: Vol. 59 (2023)
- Analysis of reported adverse liver reactions associated with drugs used to
treat patients with coronavirus disease 2019
Authors: Nayara Aparecida de Oliveira-Silva, Albert Figueras, Daniela Oliveira de Melo
Abstract: Hepatic injury has been documented in patients with coronavirus disease 2019 (COVID-19). However, pharmacotherapy can frequently impact liver alterations, given the known hepatotoxic potential of drugs not effective to treat COVID-19. The objective of the present study was to evaluate reports of suspected liver reactions to drugs used for treating COVID-19, compare their use for other indications among patients with COVID-19, and assess possible interactions between them. We obtained reports on drugs used to treat COVID-19 (tocilizumab, remdesivir, hydroxychloroquine, and/or lopinavir/ritonavir), registered on June 30, 2020, from the Food and Drug Administration Adverse Event Reporting System (FAERS) Public Dashboard. We then analyzed the risk of developing liver events with these drugs by calculating the reported odds ratios (ROR). We identified 662, 744, and 1381 reports related to tocilizumab, lopinavir/ ritonavir, and hydroxychloroquine use, respectively. The RORs (95% confidence intervals) were 6.32 (5.28-7.56), 6.12 (5.22-7.17), and 9.07 (8.00-10.29), respectively, demonstrating an increased risk of liver events among patients with COVID-19 when compared with uninfected patients. The elevated risk of reporting adverse liver events in patients with COVID-19 who receive these drugs, alone or in combination, highlights the need for careful drug selection and efforts to reduce drug combinations without notable benefits. Similar to any other condition, the use of drugs without established efficacy should be avoided.
PubDate: 2023-07-12
DOI: 10.1590/s2175-97902023e21471
Issue No: Vol. 59 (2023)
- Study of antidiabetic activity of two novel Schiff base derived dibromo
and dichloro substituted compounds in streptozotocin-nicotinamide-induced
diabetic rats
Authors: Kamelia Saremi, Sima Kianpour Rad, nazia@um.edu.my
Abstract: Schiff bases are aldehyde-or ketone-like chemical compounds in which an imine or azomethine group replaces the carbonyl group. Such compounds show various beneficial biological activities, such as anti-inflammation and antioxidants. The present study addresses comprehensiveevaluation of antidiabetic effect of two novel dibromides and dichlorides substituted Schiff bases substituted Schiff bases (2,2'-[1,2-cyclohexanediylbis (nitriloethylidyne)]bis[4-chlorophenol] (CNCP) and 2, 2'-[1,2-cyclohexanediylbis(nitriloethylidyne)]bis[4-bromophenol] (CNBP) with two different doses, high (LD) and low (LD) in streptozotocin and nicotinamide induced diabetic rats. The rats were separated into normal, untreated, treated and reference groups. Except for the normal group, diabetes traits were induced in the rest animals. Insulin level was measured, and the effect of the compounds on biochemical parameters of liver function and lipid profile were evaluated. High glucose and decreased insulin level are observed in the groups. The histological evaluation confirms that the hepatic architecture in the treated animals with a low dose of CNCP is quite similar to that of the normal hepatic structure and characterized by normal central vein, hepatocytes without any fatty alterations and mild red blood cell infiltration. CNCP (LD) and CNBP (HD) are more successful in enhancing cell survival in the diabetic rat’s liver and can be responsible for causing much healthier structure and notable morphology improvement.
PubDate: 2023-07-12
DOI: 10.1590/s2175-97902023e21159
Issue No: Vol. 59 (2023)
- HPLC-MS/MS method for determination of betamethasone in human plasma with
application to a dichorionic twin pregnancy pharmacokinetic and placental
transfers studies
Authors: Grazielle Rodrigues, Jhohann Benzi, Maria Paula Marques, Elaine Moisés, Vera Lanchote, Alessandra Marcolin
Pages: e20314 - e20314
Abstract: Betamethasone (BET) is a synthetic glucocorticoid recommended for pregnant women at imminent risk of preterm birth before 34 weeks to reduce neonatal complications. There are different techniques to describe BET plasma quantification. However, none quantified the plasmatic concentration of BET in dichorionic (DC) twin pregnancies using LC-MS. Our objectives were to develop and validate a method for quantifying BET by LC-MS for pharmacokinetic (PK) and placental transfer studies in DC twin pregnancies. Blood samples were collected after intramuscular administration of a single BET dose containing 6 mg disodium phosphate + 6 mg acetate. BET was determined in plasma by liquid-liquid extraction. The method showed linearity in the range of 2-250 ng/mL, as well as precision and accuracy with a coefficient of variation and relative standard errors ≤ 15%. Additionally, the method presented selectivity and did not present matrix or carry-over effect. Stability tests also presented coefficient of variation and relative standard errors ≤ 15%. This is the first study which describe maternal and fetal plasma concentrations of BET in a DC twin pregnancy. The BET PK parameters were AUC0-∞, CL/F, Vd/F, Cmax, Tmax of 292.20 h*ng/mL, 39.08 L/h, 278.72 L, 25.55 ng/mL and 0.58 h, respectively. The placental transfer ratios of umbilical vein/maternal vein and intervillous space/maternal vein were 0.14 and 0.19 and 0.40 and 0.27 for both twins, respectively. However, a clinical study with more subjects is imperative to confirm this higher concentration of BET in the intervillous space.
PubDate: 2023-07-10
Issue No: Vol. 59 (2023)
- Potentially inappropriate prescribing among older patients and associated
factors
Authors: Marija Jovanović, Milena Kovačević , Aleksandra Catić-Đorđević, Milica Ćulafić, Nikola Stefanović, Branka Mitić, Katarina Vučićević, Sandra Vezmar Kovačević, Radmila Veličković-Radovanović, Branislava Miljković
Abstract: The study aimed to estimate and compare the prevalence and type of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) between the STOPP/START original (v1) and updated version (v2) among older patients in various settings, as well as associated factors. The study included 440 patients attending a community pharmacy, 200 outpatients and 140 nursing home users. An increase in the prevalence of STOPP v2 (57.9%) compared to v1 (56.2%) was not statistically significant in the total sample and within each setting (p>0.05). A decrease in the prevalence of START v1 (55.8%) to v2 (41.2%) was statistically significant (p<0.001) in the total sample and within each setting (p<0.05). Drug indication (32.9%) and fall-risk medications (32.2%) were most commonly identified for STOPP v2, while cardiovascular system criteria (30.5%) were the most frequently detected for START v2. The number of medications was the strongest predictor for both STOPP v1 and v2, with odds ratio values of 1.35 and 1.34, respectively. Patients’ characteristics associated with the occurrence of STOPP and START criteria were identified. According to both STOPP/START versions, the results indicate a substantial rate of potentially inappropriate prescribing among elderly patients. The prevalence of PIMs was slightly higher with the updated version, while the prevalence of PPOs was significantly lower.
PubDate: 2023-07-03
DOI: 10.1590/s2175-97902023e22549
Issue No: Vol. 59 (2023)
- Development of a validated stability-indicating HPLC- DAD method for
dasabuvir and the characterization of its degradation products using
LC-QToF-MS/MS
Authors: Rafael Ramos Silva, Cézar Augusto da Cruz Amorim, Maria do Carmo Alves Lima, Marcelo Montenegro Rabello, Marcelo Zaldini Hernandes, Moacyr Jesus Barreto de Melo Rêgo, Maira Galdino da Rocha Pitta, Maria Danielly Lima de Oliveira, César Augusto Souza de Andrade
Abstract: A stability-indicating HPLC-DAD method was developed and validated for the simultaneous determination of dasabuvir and its degradation products in the pharmaceutical formulation. The proposed method utilized a Symmetry® C18 (4.6 x 75 mm, 3.5 µm) column, and the mobile phase consisted of an isocratic elution of formic acid (0.1%) and acetonitrile (55:45, v/v), at a flow of 1 mL min-1; analytes were detected at 244 nm. Dasabuvir was submitted to different stress degradation conditions, such as acidic, alkaline, neutral, thermal, oxidative and photolytic, and the structural elucidation of degradation products was performed using LC-QToF-MS/MS. The HPLC-DAD stability-indicating method was validated for selectivity, linearity, limit of detection and quantification, accuracy, precision and robustness, according to ICH guidelines. Dasabuvir produced two degradation products (DP1 and DP2) from the alkaline stress conditions, which were characterized in negative ion mode. Dasabuvir was linear in the range 9.78 to 136.92 µg mL-1, and DP and DP were linear in the range 2.9 to 20.2 µg mL-1 and 1.3 to 14.9 µg mL-1, respectively. The 1 2 recovery ranged between 99.16 and 100.86%, while precision ranged from 1.02 to 2.89%. As the method can effectively separate the dasabuvir from its degradation products and quantitate them, it may be employed as a stability-indicating method for the pharmaceutical formulation.
PubDate: 2023-07-03
DOI: 10.1590/s2175-97902023e22009
Issue No: Vol. 59 (2023)
- Gastroprotective potential and mechanisms of action of Hedera nepalensis
Authors: Naeem Shahzad, Irfan Anjum, Haseeb Ahsan, Alamgeer, Shahzad Khurrum Syed, Muhammad Naveed Mushtaq
Abstract: Hedera nepalensis (H. nepalensis) , belonging to the family Araliaceae, is a medicinal plant traditionally used to treat stomach problems. The current study investigated the gastroprotective potential and the mechanism of action of H. nepalensis in diclofenac-and ethanol-induced ulcer models. Anti-oxidant and lipid peroxidation inhibitory prospects of H. nepalensis were checked out by free radical scavenging assay and UV spectrophotometer respectively. Effect of H. nepalensis on the pH, gastric total acidity of gastric juice and protective effects of H. nepalensis against ulcer models have been examined. Histopathological studies have been carried out. The aqueous methanol extract of H. nepalensis (100 µg/mL) showed anti-oxidant (83.55%) and lipid peroxidation inhibitory (70.88%) potential at 1000 µg/mL; the extract had no buffer potential. The extract (400 mg/kg) significantly (81.12% and 63.46%) showed gastroprotective effect in diclofenac and ethanol-induced rat ulcer models respectively. Histopathological studies confirmed the biochemical findings. FTIR analysis showed the presence of carboxylic acid, alkanes, conjugated alkanes, aldehydes and alkyl-aryl ethers. Gallic acid, M-coumaric acid and quercetin were found by HPLC analysis. H. nepalensis exhibited significant protection against diclofenac and ethanol induced gastric damage by anti-oxidant and lipid peroxidation suppression effects suggesting potential broad utility in treatment of diseases characterized with gastric damage.
PubDate: 2023-06-29
DOI: 10.1590/s2175-97902023e20493
Issue No: Vol. 59 (2023)
- Interchangeability of medications and biopharmaceutical implication of
taking drugs with fluids other than water
Authors: Nataša Bubić Pajić, Irma Mureškić, Božana Jevđenić, Anđelka Račić, Biljana Gatarić
Abstract: The aim of this study was to compare the dissolution properties of ibuprofen solid oral dosage forms commercially available in Bosnia and Herzegovina and to estimate the influence of dissolution medium composition on the drug release. Eight products (A-H) were subjected to in vitro dissolution test using experimental conditions described in USP42-NF37. Dissolution properties of one selected product were examined in the presence of alcohol (22.2% v/v) and fruit juice (22.2% v/v). Products marked B-H complied with the pharmacopeial criteria. Dissolution profile of product B was similar with dissolution profiles of products D, E, F and G and similarity was also found between products A-D, C-G, D-G and E-F. Drug release from most of the examined preparations fitted best to the Weibull kinetic model. In the presence of alcohol in the medium, higher amount of ibuprofen was dissolved. Contrary, ibuprofen dissolved in the presence of fruit juice was significantly lower. Differences in the dissolution profiles of investigated preparations suggest that their interchangeability should be additionally considered and demonstrated with in vivo bioequivalence studies. Presence of different substances in the medium can affect dissolution properties of ibuprofen, emphasizing the importance of the patient’s compliance.
PubDate: 2023-06-29
DOI: 10.1590/s2175-97902023e22725
Issue No: Vol. 59 (2023)
- Effect of amitriptyline on learning and memory consolidation in the male
Wistar rats with an experimental model of pentylenetetrazole-induced
seizure
Authors: Soheyla Niazi, Abdolkarim Hosseini, Naser Mirazi
Abstract: Amitriptyline (AMT) was developed for the treatment of chronic and neuropathic pain. There is also evidence it may be useful in the treatment of neurodegenerative disorders. In this regard, the effect of on the experimental model of seizures and memory impairment caused by seizures in rats is investigated in the present study. Seizures in Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg, intraperitoneally (i.p.)). The anticonvulsant effect of AMT (10 and 20 mg/kg, i.p.) was evaluated in the seizure model. The effect on memory was assessed using passive avoidance (PA) learning and memory test. After behavioral tests, the animals underwent deep anesthesia and were put down painlessly. Animal serum was isolated for oxidant/antioxidant assays (malondialdehyde (MDA), and glutathione peroxidase (GPx)). Intraperitoneal injection of AMT decreased the mean number of myoclonic jerks and generalized tonic-clonic seizure (GTCS) duration and increased the mean latency of myoclonic jerk and GTCS compared to the PTZ group. Moreover, in the PA test, AMT caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that AMT was able to significantly increase GPx serum levels and significantly reduce MDA serum levels compared to the PTZ group. Overall, this study suggests the potential neuroprotective effects of the AMT drug in a model of memory impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.
PubDate: 2023-06-29
DOI: 10.1590/s2175-97902023e21606
Issue No: Vol. 59 (2023)
- IMP-1 inhibits renal cell carcinoma 786-O cell growth by targeting
EphrinB2 signaling pathway
Authors: Juan Liu, Hong Shi
Abstract: EphrinB2 plays a critical role in tumor growth. In this study, we studied the antitumor activity of imperatorin derivative IMP-1 in renal cell carcinoma (RCC) by regulating EphrinB2 pathway.. Results showed that IMP-1 inhibited the proliferation of 786-O cells in a dose- and time-dependent manner. More importantly, knockdown and transfection of EphrinB2 altered the inhibitory effect of IMP-1 on the activity of 786-O cells. IMP-1 arrested 786-O cell cycle at G0/G1 phase by decreasing the expression of cyclin D1 and cyclin E. Moreover, IMP-1 regulated Bcl-2 family proteins’ expression, thus inducing apoptosis of 786-O cells. IMP-1 down-regulated the expression of EphrinB2, Syntenin1 and PICK1. Then, IMP-1 decreased the phosphorylation of Erk1/2 and AKT. In all, IMP-1 could regulate the EphrinB2 pathway in order to inhibit 786-O cell growth by arresting the cell cycle at G0/G1 phase and inducing cell apoptosis. Thus, IMP-1 may present as a potential strategy for RCC treatment.
PubDate: 2023-06-22
DOI: 10.1590/s2175-97902023e22102
Issue No: Vol. 59 (2023)
- Evaluation of the effect of melatonin in patients with Burning mouth
syndrome
Authors: Tahereh Nosratzehi, Abolfazl Payandeh, Kosar Arbab
Abstract: The present study was carried out to evaluate the effect of Melatonin and Placebo in the patient with the Burning mouth (BMs). This double-blind, placebo-controlled randomized clinical trial study was carried out on 30 patients who were suffering from BMS. During this period patients were divided into 2 study and control groups. The study group used four 3 mg Melatonin daily and the control group received a placebo. Then the severity of the burning sensation was measured by the physician Sleep quality was measured using the VAS scale using the Petersburg questionnaire. Data in the application Enter SPSS 20 and then using T test or equivalent Nonparametric was analyzed, mean sleep score and mean severity of oral irritation before and after treatment in two the group was evaluated using T-test Independent. Level significance was considered 0.05. The results of the present study show that the use of melatonin and a placebo in patients with BMS reduces sensation and improves their sleep quality, although it may not reduce it completely. In this study severity of burning was 4.93±2.56 after treatment in the study group and 6.93±2.12 in the control group, which was statistically significant (P =0.036). No significant difference was observed between the two groups in the sleep quality score (P-value = 0.43). Using Melatonin can be a reliable way to treat pain for which there is no standard treatment to date. Although evidence suggests an association between sleep disorders and BMS, melatonin was not superior to a placebo in reducing BMS-induced burning in the present study. Identification of stressors and the ways to struggle with them, further studies with larger samples and higher oral doses, extended follow-up periods and control of psychological factors, and measurement of body mass index that may affect pharmacokinetics are recommended.
PubDate: 2023-06-22
DOI: 10.1590/s2175-97902023e21748
Issue No: Vol. 59 (2023)
- Continuous flow Aza-Michael reaction for preparing the fast-acting
synthetic opioid drug Remifentanil
Authors: Artur Vaz, João Luis Callegari Lopes, Giuliano Cesar Clososki
Abstract: Remifentanil is a modern fentanyl analogue with ultrashort-action granted by an esterase-labile methyl propanoate chain. Here, we present the development of a continuous flow methodology for the key N-alkylation step of remifentanil preparation in a biphasic, “slug-flow” regime. We screened parameters under microwave-assisted reactions, translated conditions to flow settings, and obtained remifentanil under 15-min residence time in a 1-mL microreactor, with a space-time yield of 89 mg/mL·h and 94% yield.
PubDate: 2023-06-22
DOI: 10.1590/s2175-97902023e22764
Issue No: Vol. 59 (2023)
- Consumption of benzylpenicillin as a syphilis control indicator
Authors: Emile Rodrigues da Silva, Diogo Pilger, Denise Bueno
Abstract: Syphilis is a disease with compulsory and mandatory notification to the Notifiable Diseases Information System (SINAN), with benzathine benzylpenicillin being the treatment of choice. The aim of the study was to compare the consumption of benzylpenicillin benzathine, from the dispensation, between the health regions of a capital in the southern region of the country, according to the georeferencing of notified cases of syphilis. This is a descriptive, cross-sectional, retrospective study of the use of benzylpenicillin benzathine and of reported cases of syphilis. Data on syphilis cases were obtained from notifications made in SINAN, and drug consumption data were obtained from the Municipal Health Department computerized system for Drug Dispensing from January 1st, 2019 to December 31st, 2019. Notifications and drug consumption were georeferenced according to 8 health regions. From the compilation of data, the rates of cases and consumption in relation to the population of each region were calculated. A total of 3188 notifications and a total of 35191 vials of benzathine benzylpenicillin were analyzed. The ratio of vials by SINAN notifications showed that each patient took 11 vials of the drug, which is a higher value if we consider that the complete treatment is 2 to 6 vials per case.
PubDate: 2023-06-22
DOI: 10.1590/s2175-97902023e21931
Issue No: Vol. 59 (2023)
- An analysis of pharmaceutical care for critical patients of an adult
Intensive Care Unit
Authors: Maurício Fábio Gomes, Camilo Molino Guidoni
Abstract: This work analyzed the pharmacotherapeutic problems identified by the clinical pharmacist in an intensive care unit (ICU) and the acceptance of pharmaceutical interventions in solving these problems. This is a descriptive cross-sectional retrospective study, carried out in the adult ICU of a public hospital. All patients hospitalized during the study period had their pharmacotherapy monitored and those whose stay at the ICU lasted less than 24 hours were excluded. The pharmacotherapeutic problems were classified according to type, cause, acceptability/implementation, mode of intervention, outcome and related pharmacotherapeutic group. 302 patients were followed up and 350 pharmacotherapeutic problems were identified. Most of them were classified as unnecessary drug-treatment (n=186; 53.1%). The most frequent causes were excessive drug administration (n=181; 97.3%), and antimicrobials was the main group of drugs associated to that type of problem. 350 pharmaceutical interventions were performed, highlighting “prescriber informed only” (n=178; 50.9%), with an average acceptability of 90.7%, with those carried out on site being more effective (93.4%). The number of pharmacotherapeutic problems that were totally solved was 282 (80.6%). Clinical pharmacy activities in the ICU identified, prevented and corrected pharmacotherapeutic problems, contributing to the optimization of pharmacotherapy in aspects related to the need, efficacy and safety of treatments.
PubDate: 2023-06-22
DOI: 10.1590/s2175-97902023e21345
Issue No: Vol. 59 (2023)
- Chromatographic study of sitagliptin and ertugliflozin under
quality-by-design paradigm
Authors: Sunitha Gurrala, Shiva Raj, Subrahmanyam CVS, Panikumar Durga Anumolu, Haripriya Daggupati
Abstract: The present study entails the systematic development and validation of a stability-indicating RP-HPLC method for the analysis of sitagliptin and ertugliflozin in a fixed-dose combination. Analytical quality by design (AQbD) concepts were used to define critical method variables, employing Pareto risk assessment and a Placket-Burman screening design, preceded by a Box-Behnken design with response surface analysis to optimise critical method parameters such as % acetonitrile (X1), buffer pH (X2) and column oven temperature (X3). Multiple response optimisation (Derringer’s desirability) of variables was accomplished by studying critical analytical attributes, such as resolution, retention time and theoretical plates. The title analytes were separated effectively on a PRONTOSIL C18 column at 37 °C using a mobile phase of acetonitrile:acetate buffer, pH 4.4 (36:64 percent v/v), pumped at a flow rate of 1 mL/min, and UV detection at 225 nm. Linearity was observed over a concentration range of 25-150 µg/mL and 3.75-22.5 µg/mL at retention times of 2.82 and 3.92 min for sitagliptin and ertugliflozin, respectively. The method obeyed all validation parameters of the ICH Q2(R1) guidelines. The proposed robust method allows the study of the selected drugs in pharmaceutical dosage forms as well as in drug stability studies under various stress conditions.
PubDate: 2023-06-22
DOI: 10.1590/s2175-97902023e21328
Issue No: Vol. 59 (2023)
- Effects of oxycodone hydrochloride and dezocine on hemodynamics and levels
of inflammatory factors in patients receiving gynecological laparoscopic
surgery under general anesthesia
Authors: Yufeng Tian, Zhiyong Yan, Huanxi Xu, Mingjie Zhong, Lei Tan, Yue Chen, Hao Wu
Abstract: We aimed to compare the effects of oxycodone hydrochloride and dezocine on hemodynamics and inflammatory factors in patients receiving gynecological laparoscopic surgery under general anesthesia. A total of 246 patients were divided into group A and B (n=123). Hemorheology indices were recorded 5 min after anesthesia (T0), 1 min after pneumoperitoneum (T1), when position was changed 5 min after pneumoperitoneum (T2), 15 min after pneumoperitoneum (T3), 1 min (T4) and 5 min (T5) after position was restored. Visual analogue scale scores 1, 2, 6, 12, 24 and 48 h after operation were recorded. Postoperative adverse reactions and visceral pain were observed. The expression levels of inflammatory factors were detected by enzyme-linked immunosorbent assay 12 h after operation. Compared with group A, group B had higher heart rate and mean arterial pressure at T2, lower central venous pressure and cardiac output at T1-T3, and higher systemic vascular resistance at T1-T5 (P<0.05). The incidence rate of pain syndrome in group A was lower (P<0.05). Group A had lower tumor necrosis factor-alpha and interleukin-6 expression levels and higher interleukin-10 level than those of group B (P<0.05). For gynecological laparoscopic surgery, oxycodone preemptive analgesia has superior outcomes to those of dezocine.
PubDate: 2023-06-22
DOI: 10.1590/s2175-97902023e21129
Issue No: Vol. 59 (2023)
- The Human Host Defense Peptide LL-37 Overexpressed in Lung Cell Lines by
Methanolic Extract of Valeriana officinalis
Authors: Zinat Mohammadi, Leila Pishkar , Zohre Eftekhari, Giti Barzin
Pages: e21025 - e21025
Abstract: The present study investigated the effects of valerian methanolic extract and valerenic acid on the expression of LL-37 gene and protein in A549 and MRC5 line cells. After preparing Valerian seeds, sowing them in March 2020, and harvesting the rhizome in October 2020, the extract was prepared from the valerian rhizome by maceration method. Valerian acid content was determined using high performance liquid chromatography (HPLC). Two cell lines (A549 and MRC-5) were used to study the effects of valerian extract, and the MTT test was used to evaluate cell viability. The expression of LL-37 mRNA and protein was assessed by Real-Time PCR and western blot, respectively. In vivo safety assessments and histopathological analysis were also conducted. Data was analyzed by Graphpad Prism 8 software. Valerian methanolic extract and valerenic acid upregulated the LL-37 mRNA and protein expression in both treated cell lines. Valerenic acid showed a greater effect on upregulating LL-37 expression than valerian methanolic extract. A549 cells were more sensitive to valerian methanolic extract compared to MRC5 cells, and its cell viability was reduced. Furthermore, liver and kidney-related safety assessments showed that valerian methanolic extract had no toxic effects. In general, it was concluded that the methanolic extract of valerian as well as the resulting valerenic acid as the most important component of the extract has the ability to upregulate LL-37expression. Therefore, methanolic extract of valerian and valerenic acid can be considered for improving the immune system.
PubDate: 2023-06-19
DOI: 10.1590/s2175-97902023e21025
Issue No: Vol. 59 (2023)
- Simultaneous Estimation and Validation of Four Antiepileptic Drugs from
Bulk and Formulations Using Reverse Phase HPLC
Authors: Sandhya Parameswaran
Pages: e20692 - e20692
Abstract: Epilepsy is a disorder of the central nervous system, in which the nerve cell activity in the brain is disturbed causing seizures. The objective was to develop an RP-HPLC method for consistent simultaneous quantitation of four antiepileptic drugs Levetiracetam (LVT), Lamotrigine (LTG), Phenobarbital (PBT) and Phenytoin (PTY). An isocratic method was developed on C18 column in JASCO HPLC using 5 mM potassium phosphate buffer (pH 6) and acetonitrile as the mobile phase at a flow rate of 1ml/min and detected at 230 nm using UV detector. The mean retention time for LVT, LTG, PBT and PTY were found as 2.55, 3.55, 4.65 and 5.99 minutes respectively. The method was validated as per ICH guidelines and was found to be acceptable. The %RSD value was <2.0 % thus stating the developed method was precise for the drugs in the given range. The accuracy values were within 85-115% of the recovery range. The specificity of the method was evaluated by an assay of marketed formulation, and it showed a percent content between 90-110% w/w for all the four drugs. The proposed analytical method was simple, accurate and robust and was precisely able to resolve the four major antiepileptic drugs. Hence, the current method can be applied successfully for routine examination of these drugs.
PubDate: 2023-06-19
DOI: 10.1590/s2175-97902023e20692
Issue No: Vol. 59 (2023)
- Effects of Chitosan Nanoparticles with Long Synthetic siRNAs Targeting
VEGF in Triple-Negative Breast Cancer Cells
Authors: Birnur Cömez, Jülide Akbuğa
Pages: e22304 - e22304
Abstract: Vascular endothelial growth factor (VEGF) is an essential angiogenic factor in breast cancer development and metastasis. Small interfering RNAs (siRNAs) can specifically silence genes via the RNA interference pathway, therefore were investigated as cancer therapeutics. In this study, we investigated the effects of siRNAs longer than 30 base pairs (bp) loaded into chitosan nanoparticles in triple-negative breast cancer cells, compared with conventional siRNAs. 35 bp long synthetic siRNAs inhibited VEGF gene expression by 51.2% and increased apoptosis level by 1.75-fold in MDA-MB-231 cell lines. Furthermore, blank and siRNA-loaded chitosan nanoparticles induced expression of IFN-γ in breast cancer cells. These results suggest that long synthetic siRNAs can be as effective as conventional siRNAs, when introduced into cells with chitosan nanoparticles.
PubDate: 2023-06-19
DOI: 10.1590/s2175-97902023e22304
Issue No: Vol. 59 (2023)
- Eucommia ulmoides extract attenuates angiotensin II-induced cardiac
microvascular endothelial cell dysfunction by inactivating p53
Authors: Liye Hu, Xiaolin Xu, Xunli Xiao
Pages: e22473 - e22473
Abstract: Angiotensin II (AngII) causes endothelial dysfunction. Eucommia ulmoides extract (EUE) is documented to manipulate AngII, but its impact on cardiac microvascular endothelial cell (CMVEC) function remains unknown. This study determines the effects of EUE on AngII-treated CMVECs. CMVECs were treated with different concentrations of AngII or EUE alone and/or the p53 protein activator, WR-1065, before AngII treatment, followed by examinations of the apoptotic, migratory, proliferative, and angiogenic capacities and nitric oxide (NO), p53, von Willebrand factor (vWF), endothelin (ET)-1, endothelial NO synthase (eNOS), manganese superoxide dismutase (MnSOD), hypoxia-inducible factor (HIF)-1α, and vascular endothelial growth factor (VEGF) levels. AngII induced CMVEC dysfunction in a concentration-dependent manner. EUE enhanced the proliferative, migratory, and angiogenic capacities and NO, MnSOD, and eNOS levels but repressed apoptosis and vWF and ET-1 levels in AngII-induced dysfunctional CMVECs. Moreover, AngII increased p53 mRNA levels, p-p53 levels in the nucleus, and p53 protein levels in the cytoplasm and diminishes HIF-1α and VEGF levels in CMVECs; however, these effects were counteracted by EUE treatment. Moreover, WR-1065 abrogated the mitigating effects of EUE on AngII-induced CMVEC dysfunction by activating p53 and decreasing HIF-1α and VEGF expression. In conclusion, EUE attenuates AngII-induced CMVEC dysfunction by upregulating HIF-1α and VEGF levels via p53 inactivation.
PubDate: 2023-06-19
DOI: 10.1590/s2175-97902023e22473
Issue No: Vol. 59 (2023)
- Effects of chemical and green nano-zinc oxide on histological changes,
oxidative stress, and apoptosis in rat kidney associated with cisplatin
Authors: Naeem Erfani Majd, Mohammad Reza Tabandeh, Shima Hosseinifar, Annahita Rezaie, Hajar Papi
Abstract: Cisplatin (CP) is used to treat various tumors. A main restriction of cisplatin is nephrotoxicity. This study aimed to evaluate the protective effects of ZnONPs on cisplatin-induced oxidative stress and rat kidney tissue damage. Eighty adult male Wistar rats (250g-270g) were divided into ten groups: Control (CON), Sham (SH), Bulk ZnO (BZnO), Chemical ZnONPs (ChZnONPs), Green ZnONPs (GrZnONPs), Cisplatin (CP), Cisplatin+BulkZnO (CP+BZnO), Cisplatin+Green ZnONPs (CP+GrZnONPs), Cisplatin+Chemical ZnONPs (CP+ChZnONPs), Cisplatin+Explant (CP+EX). CP was i.p administered 5mg/kg/week and BZnO, ChZnONPs and GrZnONPs were i.p administered at a dose of 5mg/kg/day. After 30 days of the treatment, the expression of apoptosis/anti apoptosis related genes oxidant/antioxidant factors and histological changes in the were studied. The CP-treated group showed a decrease in body weight, while the Co-administration of ZGNPs to CP-treated rats showed a significant increase compared to the CP group. The results showed that the increased mRNA level of bax, MDA and the decreased mRNA level of bcl2, SOD and CAT activities in kidney of CP group were improved when animals were treated with ZnO NPs. Our results showed that GrZnONPs, ChZnONPs and BZnO had the potential to protect against oxidative stress and cisplatin-induced neurotoxicity that this protective effect was more evident in GrZnONPs.
PubDate: 2023-06-15
DOI: 10.1590/s2175-97902023e20960
Issue No: Vol. 59 (2023)
- Microemulsions Improve Topical Protoporphyrin IX (PpIX) Delivery for
Photodynamic Therapy of Skin Cancer
Authors: Paula Ângela de Souza Marinho Leite, Nádia Campos de Oliveira Miguel, Maria Pierre
Abstract: We report here microemulsions (MEs) for topical delivery of protoporphyrin IX (PpIX) for Photodynamic Therapy (PDT) of skin cancers. Selected MEs consisting of Oil/Water (O/W) bicontinuous (BC) and Water/Oil (W/O) preparations were characterized as to pH, nanometric size, zeta potential, drug content, and viscosity. Sustained in vitro PpIX release was achieved from MEs 2A (O/W), 10B (BC) and 16B (W/O) through an artificial membrane for up to 24 h, characterizing MEs as drug delivery systems. None of these MEs showed permeation through the skin, demonstrating the required topical effect. After 4 h, in vitro retention of PpIX in the stratum corneum (SC) was higher from both ME 10B and control (PpIX at 60 µg/mL in PEG 300). However, in the Epidermis + Dermis ([Ep + D]), retention from ME 10B and ME 16B was ~40 times higher compared to control. Confocal Laser Scanning Microscopy (CLSM) showed higher fluorescence intensity in the SC for both control and ME 10B, whereas ME 10B fluorescence was higher in [Ep+D]. The results indicate that ME 10B is suitable for PpIX encapsulation, showing good characteristics and a localized effect for a potential delivery system for PDT-associated treatments of skin cancers.
PubDate: 2023-06-15
DOI: 10.1590/s2175-97902023e21920
Issue No: Vol. 59 (2023)
- Phytochemical Analysis and Evaluation of Antifungal and Antioxidant
Activities of Essential Oil of Fruits from Juniperus oxycedrus L. Obtained
from Morocco
Authors: Ahmed Elfallaki elidrissi, Ibrahim Mssillou, Abdelkrim Agour, Meryem Tourabi, Ghizlane Nouioura, Badiaa Lyoussi, Derwich Elhoussine
Abstract: The present study was aimed at conducting phytochemical analysis and evaluating the in vitro antifungal and antioxidant activities of the essential oil obtained from the fruits of J. oxycedrus L. Hydro-distillation was used to extract the essential oil from the fruits of Juniper oxycedrus. The essential oil was analyzed using gas chromatography with a flame ionization detector (GC-FID) and gas chromatography coupled with mass spectrometry (GC/MS). The antioxidant activity of the essential oil against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals was determined in vitro using varying concentrations of the essential oil and vitamin C as a standard antioxidant compound. A disc diffusion test was employed to evaluate the antifungal activity of the essential oil against two test fungal strains, Penicillium citrinum, and Aspergillus niger. The results revealed that 49 constituents were identified in fruit oil, representing 91.56% of the total oil and the yield was 1.58%. Juniper fruit oil was characterized by having high contents of β-pinene (42.04%), followed by limonene (15.45%), sabinene (9.52%), α-pinene (5.21%), (E)-caryophyllene (3.77%), ρ-cymene (1.56%), caryophyllene oxide (2.02%), and myrcene (1.02%). The radical scavenging activity (% inhibition) of the essential oil was highest (81.87± 2.83%) at a concentration of 200 µg/mL. The essential oil of J. oxycedrus exhibited antifungal activity against A. niger and P. citrinum with minimum inhibitory concentration values (MIC) ranging from 2.89 to 85.01 µl/mL. The findings of the study reveal that the antioxidant and antifungal properties of J. oxycedrus essential oil and their chemical composition are significantly correlated.
PubDate: 2023-06-15
DOI: 10.1590/s2175-97902023e21088
Issue No: Vol. 59 (2023)
- Evaluation of the effect of melatonin in patients with Burning mouth
syndrome
Authors: Tahereh Nosratzehi, Abolfazl Payandeh, Kosar Arbab
Abstract: The present study was carried out to evaluate the effect of Melatonin and Placebo in the patient
with the Burning mouth (BMs). This double-blind, placebo-controlled randomized clinical trial
study was carried out on 30 patients who were suffering from BMS. During this period patients
were divided into 2 study and control groups. The study group used four 3 mg Melatonin
daily and the control group received a placebo. Then the severity of the burning sensation was
measured by the physician Sleep quality was measured using the VAS scale using the Petersburg
questionnaire. Data in the application Enter SPSS 20 and then using T test or equivalent
Nonparametric was analyzed, mean sleep score and mean severity of oral irritation before and
after treatment in two the group was evaluated using T-test Independent. Level significance was
considered 0.05. The results of the present study show that the use of melatonin and a placebo
in patients with BMS reduces sensation and improves their sleep quality, although it may not
reduce it completely. In this study severity of burning was 4.93±2.56 after treatment in the study
group and 6.93±2.12 in the control group, which was statistically significant (P =0.036). No
significant difference was observed between the two groups in the sleep quality score (P-value
= 0.43). Using Melatonin can be a reliable way to treat pain for which there is no standard
treatment to date. Although evidence suggests an association between sleep disorders and
BMS, melatonin was not superior to a placebo in reducing BMS-induced burning in the present
study. Identification of stressors and the ways to struggle with them, further studies with larger
samples and higher oral doses, extended follow-up periods and control of psychological factors,
and measurement of body mass index that may affect pharmacokinetics are recommended
PubDate: 2023-06-15
DOI: 10.1590/s2175-97902023e21748
Issue No: Vol. 59 (2023)
- Bioactivity-guided isolation of the antidiabetic principle in Pterocarpus
Santalinoides leaf extract
Authors: Kelechi Gideon Madubuike
Abstract: Pterocarpus santalinoides is used in Nigerian ethnomedicine to treat diabetes mellitus. This study aimed to establish the antidiabetic property of the plant, and isolate and characterize its active principle. Dried and pulverized leaves (500 g) of P. santalinoides were extracted with 1.8 L of 80 % hydromethanol by cold maceration. The dried extract (10 g) was partitioned into n-hexane, ethyl acetate (EtOAc), n-butanol, and water. Antidiabetic activitiy-guided isolation by column chromatographic separation of the EtOAc soluble and purification of the sub-fractions by repeated preparative thin layer chromatography (pTLC) yielded a C-glycosyl flavonoid, identified as isovitexin. The chemical structure was elucidated based on high-resolution mass spectroscopy, 1D, and 2D nuclear magnetic resonance spectroscopic analyses. Alloxan-induced diabetic rat model was adopted for antidiabetic screening. The extract of P. santalinoides (100-200 mg/kg), fraction F4 (50 mg/kg), sub-fraction F4.3 (10 mg/kg), and the semi-purified compound F4.3.2 (5 mg/kg) significantly (p<0.05) reduced the fasting blood glucose of alloxan-induced diabetic rats, causing 48.4, 69.4, 57.7 and 64.5 % antidiabetic activity respectively, compared with > 68 % recorded in glibenclamide (2 mg/kg) control. These results reveal that isovitexin is the antidiabetic principle in P. santalinoides.
PubDate: 2023-06-13
DOI: 10.1590/s2175-97902023e21726
Issue No: Vol. 59 (2023)
- Locust bean gum hydrogels are bioadhesive and improve indole-3-carbinol
cutaneous permeation
Authors: Carina Dinah Merg, Jéssica Brandão Reolon, Giancarlo Cervo Rechia, Letícia Cruz
Abstract: The locust bean gum (LBG) is a polysaccharide with thickening, stabilizing and gelling properties and it has been used in the preparation of pharmaceutical formulations. Hydrogels (HGs) are obtained from natural or synthetic materials that present interesting properties for skin application. This study aimed to develop HGs from LBG using indole-3-carbinol (I3C) as an asset model for cutaneous application. HGs were prepared by dispersing LBG (2%, 3% and 4% w/v) directly in cold water. The formulations showed content close to 0.5 mg/g (HPLC) and pH ranging from 7.25 to 7.41 (potentiometry). The spreadability factor (parallel plate method) was inversely proportional to LBG concentration. The rheological evaluation (rotational viscometer) demonstrated a non-Newtonian pseudoplastic flow behavior (Ostwald De Weale model), which is interesting for cutaneous application. The HET-CAM evaluation showed the non-irritating characteristic of the formulations. The bioadhesive potential demonstrated bioadhesion in a concentration-dependent manner. Permeation in human skin using Franz cells showed that the highest LBG concentration improved the skin distribution profile with greater I3C amounts in the viable skin layers. The present study demonstrated the feasibility of preparing HGs with LBG and the formulation with the highest polymer concentration was the most promising to transport active ingredients through the skin.
PubDate: 2023-06-13
DOI: 10.1590/s2175-97902023e21770
Issue No: Vol. 59 (2023)
- Statistical process control of manufacturing tablets for antiretroviral
therapy
Authors: Nataly Paredes da Rocha, Osvaldo Cirilo da Silva, Eduardo José Barbosa, Gidel Soares, Roberto Oliveira, Lis Marie Monteiro, Nádia Araci Bou-Chacra
Abstract: In this study, the manufacturing process of lamivudine (3TC) and zidovudine (AZT) tablets (150+300 mg respectively) was evaluated using statistical process control (SPC) tools. These medicines are manufactured by the Fundação para o Remédio Popular “Chopin Tavares de Lima” (FURP) laboratory, and are distributed free of charge to patients infected with HIV by the Ministry of Health DST/AIDS national program. Data of 529 batches manufactured from 2012 to 2015 were collected. The critical quality attributes of weight variation, uniformity of dosage units, and dissolution were evaluated. Process stability was assessed using control charts, and the capability indices Cp, Cpk, Pp, and Ppk (process capability; process capability adjusted for non-centered distribution; potential or global capability of the process; and potential process capability adjusted for non-centered distribution, respectively) were evaluated. 3TC dissolution data from 2013 revealed a non-centered process and lack of consistency compared to the other years, showing Cpk and Ppk lower than 1.0 and the chance of failure of 2,483 in 1,000,000 tablets. Dissolution data from 2015 showed process improvement, revealed by Cpk and Ppk equal to 2.19 and 1.99, respectively. Overall, the control charts and capability indices showed the variability of the process and special causes. Additionally, it was possible to point out the opportunities for process changes, which are fundamental for understanding and supporting a continuous improvement environment.
PubDate: 2023-06-13
DOI: 10.1590/s2175-97902023e22099
Issue No: Vol. 59 (2023)
- Preformulation studies for the development of a microemulsion formulation
from Ambrosia peruviana All., with anti-inflammatory effect
Authors: Yuri Paola Palacio Taborda, Jenny Castro, Valquiria Linck Bassani, Luis Alberto FrancO, Carlos-Alberto Bernal Rodríguez
Abstract: Natural products are considered an important source of the therapeutic arsenal currently available. Among these alternatives are the seeds of Ambrosia peruviana (altamisa), whose extract has shown an anti-inflammatory effect. The main objective of this work was to perform a preformulation study of Ambrosia peruviana seeds ethanolic extract, where the main factors that affect the physical, chemical, and pharmacological stability of the extract were evaluated, as well as a compatibility study by differential scanning calorimetry (DSC) analysis against different excipients. A dry extract was obtained by rotary evaporation of the seeds macerated with 96% ethanol. The anti-inflammatory activity was determined by measuring its effect on NO production in RAW 264.7 macrophages, stimulated with LPS. The results showed that the dry extract maintained its stability over time when stored at a temperature of 4 and 25ºC, demonstrating its biological activity, the content of phenolic compounds, and its physicochemical parameters remain practically invariable. However, when exposed to high temperatures (60 ºC) it was affected. The thermal analysis revelated that the behavior of most of the selected excipients and the dry extract was maintained, which indicates that it did not present incompatibilities, therefore they can be candidates for formulating a microemulsion.
PubDate: 2023-06-13
DOI: 10.1590/s2175-97902023e22505
Issue No: Vol. 59 (2023)
- Process optimization of physicochemical properties of spray-dried
Hydrocotyle umbellata L. extract
Authors: Matheus Gabriel de Oliveira, Guilherme Gomes Moreira, Andressa Tuane Santana Paz, Thiago Levi Silva Oliveira, Luís Antônio Dantas Silva, Edemilson Cardoso da Conceição, Leonardo Luiz Borges, Vinicius Barreto da Silva, José Realino de Paula
Pages: e21211 - e21211
Abstract: Hydrocotyle umbellata L., Araliaceae, is a species that is recommended in Ayurvedic medicine for its effects on the central nervous system, such as anxiolytic and memory-stimulant effects. Despite the medicinal potential of this species, its phytopharmaceutical and technological potential to produce standardized extracts has not been investigated. This study analyzes the influence of spray drying parameters on the contents of the chemical markers (total phenolic, total flavonoid, and hibalactone) and the functional properties of H. umbellata extract. The optimization of drying conditions was performed using a central composite design combined with response surface methodology and desirability function approach. The mathematical models fitted to experimental data indicated that all the evaluated drying parameters significantly influenced the chemical contents. The optimal conditions were: inlet temperature of 120 °C, feed flow rate of 4 mL min-1, and colloidal silicon dioxide:maltodextrin ratio of 16%:4%. Under these conditions, the powder samples had spherical particles and desirable physicochemical and functional properties, such as low water activity and moisture content, good product recovery, reconstitution, and flowability. Thus, spray drying might be a promising technique for processing standardized H. umbellata extracts.
PubDate: 2023-05-26
DOI: 10.1590/s2175-97902023e21211
Issue No: Vol. 59 (2023)
- Nephroprotective effects of Lippia sidoides ethanolic extract against
ischemia/reperfusion-induced acute kidney injury
Authors: Marcus Felipe Bezerra da Costa, Tiago Lima Sampaio, Isabella Evelyn Prado de Azevedo, Dânya Lima Bandeira, Igor Lima Soares, Gdayllon Cavalcante Meneses, Samilly Albuquerque Ribeiro, Janaina Serra Azul Monteiro Evangelista, Mary Anne Medeiros Bandeira, Alexandre Braga Libório, Alice Maria Costa Martins
Pages: e21371 - e21371
Abstract: Ischemia/reperfusion injury (I/R) is commonly related to acute kidney injury (AKI) and oxidative stress. Antioxidant agents are used to treat this condition. Lippia sidoides is a brazillian shrub with anti-inflammatory and anti-oxidative properties. Thus, the aim of this study is to evaluate the effect of Lippia sidoides ethanolic extract (LSEE) on in vivo and in vitro models of AKI induced by I/R. Male Wistar rats were submitted to unilateral nephrectomy and ischemia on contralateral kidney for 60 min via clamping followed by reperfusion for 48 h. They were divided into four groups: Sham, LSEE (sham-operated rats pre-treated with LSEE), I/R (rats submitted to ischemia) and I/R-LSEE (rats treated with LSEE before ischemia). Kidney tissues homogenates were used to determine stress parameters and nephrin expression. Plasma and urine samples were collected for biochemical analysis. I/R in vitro assays were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and flow cytometry assays in Rhesus Monkey Kidney Epithelial Cells (LLC-MK2). The LSEE treatment prevented biochemical and nephrin expression alterations, as well as oxidative stress parameters. In the in vitro assay, LSEE protected against cell death, reduced the reactive oxygen species and increased mitochondrial transmembrane potential. LSEE showed biotechnological potential for a new phytomedicine as a nephroprotective agent.
PubDate: 2023-05-26
DOI: 10.1590/s2175-97902023e21371
Issue No: Vol. 59 (2023)
- Propyl (E)-3-(furan-2-yl) Acrylate
Authors: Paulo Costa, Thales Santos, Jaqueline Ramos, Jonh Santos, Francinalva Medeiros, Juliano Freitas, Wylly Araújo de Oliveira
Abstract: The genus Candida represents the main cause of infections of fungal origin. Some species stand out as disease promoters in humans, such as C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis. This study evaluated the antifungal effects of propyl (E)-3-(furan-2-yl) acrylate. The minimum inhibitory concentration of the synthetic compound, amphotericin B and fluconazole alone against four species of Candida ranged from 64 to 512 μg/mL, 1 to 2 μg/mL, and 32 to 256 μg/mL, respectively. The synergistic effect of the test substance was observed when associated with fluconazole against C. glabrata, there was no antagonism between the substances against any of the tested strains. The potential drug promoted morphological changes in C. albicans, decreasing the amount of resistance, virulence, and reproduction structures, such as the formation of pseudohyphae, blastoconidia, and chlamydospores, ensuring the antifungal potential of this substance. It was also possible to identify the fungicidal profile of the test substance through the study of the growth kinetics of C. albicans. Finally, it was observed that the test compound inhibited the ergosterol biosynthesis by yeast.
PubDate: 2023-05-22
DOI: 10.1590/s2175-97902023e22045
Issue No: Vol. 59 (2023)
- Development and evaluation of wafer loaded with sertaconazole solid
dispersion for the treatment of oral candidiasis
Authors: Horieh Hajhashemi, Somayeh Taymouri, Fatemeh Shafiee
Abstract: Candidiasis is one of the most common fungal infections of oral cavity in humans, causing great oral discomfort, pain and aversion to food. To develop more effective antifungal systems for the treatment of oral candidiasis, an oral mucoadhesive wafer containing sertaconazole solid dispersion (STZ-SD) was developed in this study. Dispersion of STZ in Soluplus® as a solubility enhancement excipient was done by melting, solvent evaporation and freeze drying method at various STZ to Soluplus® ratios. The optimized STZ-SD was then incorporated in the sodium carboxymethyl cellulose (SCMC) gel, xanthan gum gel, or their combination to prepare the lyophilized wafers. The swelling capacity, porosity, and mechanical, release and mucoadhesive properties of the wafers, together with their antifungal activity, were then evaluated. The melting method sample with the ratio of 8:1 showed the best results in terms of saturation solubility and dissolution rate. The STZ-SD-composite wafer exhibited higher hardness and mucoadhesion, as compared to those made of the SCMC polymer. The STZ-SD-wafer also exhibited a greater antifungal effect when compared to the STZ-wafer. The present study, thus, suggested that the STZ-SD-wafer could serve as a novel effective delivery system for oral candidiasis treatment.
PubDate: 2023-05-22
DOI: 10.1590/s2175-97902023e22452
Issue No: Vol. 59 (2023)
- Metabolic study of trimetazidine using ultrahigh performance liquid
chromatographytandem mass spectrometry
Authors: Kamila Chomanicova, Élida Alechaga Silva, Rosa Ventura Alemany
Abstract: In the present study, the application of ultra-high performance liquid chromatography-tandem mass spectrometry allowed us to study of known-as well as hitherto unknown-trimetazidine (TMZ) metabolites in human urine and to propose their renal excretion profiles. Urine samples from a healthy volunteer were analyzed at baseline and at 0-4 h, 4-8 h, 8-12 h, and 12-24 h after a single dose of TMZ. A dilute-and-shoot procedure was used as sample treatment before separation. Full-scan spectra of possible metabolites were acquired. Additionally, product ion scan spectra of precursor ions of interest were also acquired at two collision energies. Intact TMZ was a major excretion product, with a maximum concentration at 4-8 h after administration. Moreover, five minor metabolites were observed, namely trimetazidine-N-oxide (M1), N-formyl trimetazidine (M2), desmethyl-trimetazidine O-sulfate (M3), desmethyl-trimetazidine O-glucuronide (M4), and desmethyl-trimetazidine-N-oxide-O-glucuronide (M5). Metabolite M5 has not previously been reported. Excretion curves were constructed based on the chromatographic peak areas of specific mass transitions (precursor ion > product ion) related to each of the detected metabolites.
PubDate: 2023-05-22
DOI: 10.1590/s2175-97902023e22453
Issue No: Vol. 59 (2023)
- In-Vitro and Ex-Vivo Evaluation of Transfersomal Gel of Methotrexate
Authors: Chetna Modi, Praful Bharadia
Abstract: Methotrexate on its oral and intravenous administration results in unwanted adverse effects. This drawback can be overcome by transdermal delivery because of its painless objective for systemic drug administration. Transfersomes are ultra-deformable vesicles with the flexibility to reach deeper tissues of the skin. The objective of this research work was to develop methotrexate transfersomal gel by thin film hydration technique, evaluated for entrapment efficiency, deformability, mean vesicle size, and stability, and incorporated into carbopol gel for ease of handling and skin applicability for a longer period of retention on skin. MTX-TFS gel & conventional gel were characterized for consistency, transparency, viscosity, and pH. Ex-vivo skin permeation studies were performed using abdominal goat skin and drug release kinetic parameters and transdermal flux were calculated using mathematical models. The results indicate that MTX was successfully entrapped (84.77 ± 2.35 %w/w) in transfersomes having 240±1.6 nm vesicle sizes and 27.13±0.7 deformability index. The gel was permeated through the skin at a rate of 28.12±2.58 µg/cm2/hr as compared to the conventional gel (10.35±2.14 µg/cm2/ hr). From the study, it was concluded that the MTX-TFS gel can be used as a possible substitute for the conventional formulation for transdermal drug delivery due to 3 times improvement in transdermal flux.
PubDate: 2023-05-22
DOI: 10.1590/s2175-97902023e22643
Issue No: Vol. 59 (2023)
- Starch-based orodispersible film for diclofenac release
Authors: Fabio Tamanini, Beatriz Sakakibara Moraes, Creusa Sayuri Tahara Amaral, Antonio José Felix Carvalho, Eliane Trovatti
Abstract: The form of drug administration affects the success of treatment, since it can influence adherence of the patient to the therapy. The use of orodispersible films has emerged as a way to overcome some drawbacks of conventional methods of drug delivery, especially for patients experiencing difficulty in swallowing. These films are prepared using a matrix that incorporates the drug and contains other substances that confer the properties of the system. The present work describes the use of thermoplastic starch as a carrier for the model drug diclofenac, including film preparation and testing of its orodispersible potential. Preparation of the film employed a microwave oven to gelatinize and plasticize corn starch, with incorporation of the model drug, followed by solvent-casting. The samples were characterized using mechanical tests, analyses of water uptake and water content, and Fourier transform infrared spectroscopy. The results indicated that the film presented promising properties as an alternative system for oral drug administration, with good incorporation and distribution of the drug in the matrix. The material displayed satisfactory mechanical properties, which are crucial for this type of material, due to the need for oral administration and handling before use.
PubDate: 2023-05-22
Issue No: Vol. 59 (2023)
- Development and clinical application of hydrogel formulations containing
papain and urea for wound healing
Authors: Thais Menezes dos Santos, Danieli Silva Feijó de Sousa, Karina Chamma di Piero, Adriane Regina Todeschini, Wagner Barbosa Dias, Catarina Amorim Oliveira, Elisabete Pereira dos Santos, Mariana Sato de Souza Bustamante Monteiro, Maria Kátia Gomes, Cristiano dos Reis Moura, Pedro Antônio Castelo Teixeira, Eduardo Ricci-Junior, Zaida Maria Faria de Freitas
Abstract: Hydrogels are used for wound treatment, as they may contain one or more active components and protect the wound bed. Papain is one of the active substances that have been used with this purpose, alongside urea. In this paper, carboxypolymethylene hydrogels containing papain (2% and 10% concentrations) and urea (5% concentration) were produced. Physical-chemical stability was performed at 0, 7, 15 and 30 days at 2-8ºC, 25ºC and 40ºC, as well as the rheological aspects and proteolytic activity of papain by gel electrophoresis. Clinical efficacy of the formulations in patients with lower limb ulcers was also evaluated in a prospective, single-center, randomized, double-blind and comparative clinical trial. The results showed 7-day stability for the formulations under 25ºC, in addition to approximately 100% and 15% of protein activity for 10% and 2% papain hydrogel, respectively. The rheological profile was non-Newtonian for the 10% papain hydrogel tested. There were no significant differences regarding the mean time for healing of the lesions, although 10% papain presented a better approach to be used in all types of tissue present in the wound bed.
PubDate: 2023-05-22
DOI: 10.1590/s2175-97902023e201090
Issue No: Vol. 59 (2023)
- Hematological and coagulation parameters as predictors of death by
Coronavirus disease in hospitalized patients
Authors: Gabriel Macedo Costa Guimarães, Renan Faustino, Any Caroline Oliveira, Lilian Santos Alves, Fabiana Rabe Carvalho, Katia Lino Baptista, Hugo Henrique Kegler dos Santos, Jorge Reis Almeida, Thalia Medeiros, Andrea Alice Silva
Pages: e21798 - e21798
Abstract: This study aimed to evaluate the hematological and coagulation parameters according to the clinical outcomes of coronavirus disease (COVID-19). We analyzed the hematological and coagulation parameters of hospitalized patients with COVID-19 at admission, and two and three weeks during hospitalization. To assess the performance of these parameters in predicting poor outcomes, receiver operating characteristic (ROC) curves were created. We studied 128 patients with COVID-19 (59.2±17.7 years, 56% male). Non-survivors (n=54, 42%) presented significant alterations in hematological and coagulation parameters at admission, such as increased in white blood cells (WBC), neutrophil, and band cell counts, as well as elevated prothrombin time (PT), activated partial thromboplastin time, and D-dimer levels. During follow-up, the same group presented a gradual increase in D-dimer and PT levels, accompanied by a reduction in PT activity, hemoglobin, and red blood cell count (RBC). ROC curves showed that WBC, neutrophil, and band cell counts presented the best area under the curve (AUC) values with sensitivity and specificity of >70%; however, a logistic regression model combining all the parameters, except for RBC, presented an AUC of 0.89, sensitivity of 84.84%, and specificity of 77.41%. Our study shows that significant alterations in hematological and coagulation tests at admission could be useful predictors of disease severity and mortality in COVID-19.
PubDate: 2023-05-22
DOI: 10.1590/s2175-97902023e21798
Issue No: Vol. 59 (2023)
- Selective photodynamic effects on cervical adenocarcinoma cells provided
by F127 Pluronic®-based micelles modulating hypericin delivery
Authors: Kayane Harumi Mashiba, Lucimara Rofrigues Carobeli, Maria Vítoria Felipe de Souza, Lyvia Eloiza de Freitas Meirelles, Natália Lourenço Mari, Gabriel Batista César, Renato Sonchini Gonçalves, Wilker Caetano, Edilson Damke, Vânia Ramos Sela da Silva, Gabrielle Marconi Zago Ferreira Damke, Marcia Edilaine Lopes Consolaro
Pages: e22459 - e22459
Abstract: Cervical cancer is a leading cause of death among women. The endocervical adenocarcinoma (ECA) represents an aggressive and metastatic type of cancer with no effective treatment options currently available. We evaluated the antitumoral and anti-migratory effects of hypericin (HYP) encapsulated on Pluronic F127 (F127/HYP) photodynamic therapy (PDT) against a human cell line derived from invasive cervical adenocarcinoma (HeLa) compared to a human epithelial cell line (HaCaT). The phototoxicity and cytotoxicity of F127/HYP were evaluated by the following assays: colorimetric assay, MTT, cellular morphological changes by microscopy and long-term cytotoxicity by clonogenic assay. In addition, we performed fluorescence microscopy to analyze cell uptake and subcellular distribution of F127/HYP, cell death pathway and reactive oxygen species (ROS) production. The PDT mechanism was determined with sodium azide and D-mannitol and cell migration by wound-healing assay. The treatment with F127/HYP promoted a phototoxic result in the HeLa cells in a dose-dependent and selective form. Internalization of F127/HYP was observed mainly in the mitochondria, causing cell death by necrosis and ROS production especially by the type II PDT mechanism. Furthermore, F127/HYP reduced the long-term proliferation and migration capacity of HeLa cells. Overall, our results indicate a potentially application of F127/HYP micelles as a novel approach for PDT with HYP delivery to more specifically treat ECA.
PubDate: 2023-05-22
DOI: 10.1590/s2175-97902023e22459
Issue No: Vol. 59 (2023)
- Applicability of [18F]FDG/PET for investigating rosmarinic acid
preconditioning efficacy in a global stroke model in mice
Authors: Elaine Vasconcelos dos Santos, Brígida Gomes de Almeida Schirmer, Jousie Michel Pereira, Natane Vitória Silva Cardoso, Carlos Malamut , Mércia Oliveira
Abstract: Positron emission tomography (PET) is a non-invasive nuclear imaging technique that uses radiotracers to track cell activity. The radiopharmaceutical 18F-fluoro-2-deoxyglucose ([18F] FDG) is most commonly used in nuclear medicine for the diagnosis of various diseases, including stroke. A stroke is a serious condition with high mortality and morbidity rates. Rosmarinic acid (RA) is a promising therapeutic agent that exerts neuroprotective effects against various neurological diseases. Therefore, this study aimed to evaluate the applicability of [18F]FDG/PET for investigating the neuroprotective effects of RA in case of a global stroke model in mice. The [18F]FDG/PET technique facilitates the observation of ischemia and reperfusion injuries in the brain. Moreover, the recovery of glucose metabolism in three specific brain regions, the striatum, superior colliculus, and inferior colliculus, was observed after preconditioning with RA. It was concluded that the [18F]FDG/PET technique may be useful for stroke diagnosis and the assessment of treatment response. In addition, a long-term longitudinal study using biochemical analysis in conjunction with functional imaging may provide further conclusive results regarding the effect of RA on cerebral ischemia.
PubDate: 2023-05-19
DOI: 10.1590/s2175-97902023e21555
Issue No: Vol. 59 (2023)
- Protective Effect of Combined Metoprolol and Atractylenolide I in Rats
with Acute Myocardial Infarction via Modulation of the
SIRT3/β-CATENIN/PPAR-γ Signaling Pathway Article
Authors: Weijian Zhou, Jing Liu, Zhongli Sun, Yongpeng Dong, Meiming Zhu, Li Li
Abstract: Herein, we examined the protective effect of metoprolol combined with atractylenolide I (Atr I) in acute myocardial infarction (AMI) by regulating the SIRT3 (silent information regulator 3)/β-catenin/peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway. Briefly, 50 rats were randomly divided into the sham operation, model, metoprolol, Atr I, and combination metoprolol with Atr I groups (combined treatment group). The AMI model was established by ligating the left anterior descending coronary artery. After treatment, infarct size, histopathological changes, and cell apoptosis were examined using 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, and the TUNEL assay. The left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and left ventricular mass index (LVMI) were detected by echocardiography. Endothelin-1 (ET-1), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels were detected using enzyme-linked immunosorbent assays. Furthermore, we measured lactate dehydrogenase (LDH), creatine kinase (CK) isoenzyme (CK-MB), and CK levels. Western blotting was performed to determine the expression of SIRT3, β-catenin, and PPAR-γ. Herein, the combined treatment group exhibited increased levels of LVEF, LVFS, and NO, whereas LVMI, ET-1, TNF-α, IL-6, LDH, CK-MB, and CK levels were decreased. Importantly, the underlying mechanism may afford protection against AMI by increasing the expression levels of SIRT3, β-catenin, and PPAR-γ.
PubDate: 2023-05-19
DOI: 10.1590/s2175-97902023e21639
Issue No: Vol. 59 (2023)
- Antioxidant, Antidiabetic and Lipid Profiling of Spermadicyton Suaveolens
in Streptozotocin (STZ) Induced Diabetic Rats Article
Authors: Pratik Maske, Popat Kumbhar, Ashok Wali, John Disouza, Maya Sharma
Abstract: Diabetes is a life-threatening disease, and currently available synthetic medicines for treating diabetes are associated with various side effects. Therefore, there is an unmet need to develop herbal remedies against diabetes as an alternative to synthetic medicines. Although local healers use the roots of Spermadicyton suaveolens (SS) to manage diabetes, there is negligible research to validate its antidiabetic properties. The present investigation aims to the assess the antioxidant, antidiabetic, and antihyperlipidemic potential of the ethanolic extract of S. Suaveolen’s roots (EESS) on streptozotocin (STZ) induced diabetic rats. The extract was screened for in vitro antioxidant and antidiabetic activity. The in vivo antidiabetic potential of EESS (at 200 and 400 mg/kg) was studied on STZ-induced diabetic rats for 20 days. The EESS displayed significant (p<0.05) antidiabetic and antioxidant properties. The administration of 200 mg/kg and 400 mg/kg EESS in STZ-induced diabetic rats significantly reduced hyperglycemia, and restored antioxidant enzymes and lipid profile-a high density lipoprotein (HDL) increased by the administration of a single dose of streptozotocin. Thus, EESS could be a promising herbal medicine in the treatment of diabetes and hyperlipidemia.
PubDate: 2023-05-19
DOI: 10.1590/s2175-97902023e21820
Issue No: Vol. 59 (2023)
- Applicability of an HPLC method for analysis of alcoholic and glycolic
Brazilian green-propolis extracts
Authors: Camila Vecchi, Rafaela Said dos Santos, Marcos Bruschi
Abstract: Brazilian green propolis has been widely used in food and pharmaceutical products due to its valuable source of phenolic compounds and versatile biological activities. The development and validation of analytical methods are extremely useful for the characterization and quality control of products containing propolis. Therefore, the aim of this study was to optimize, validate and investigate the applicability of a reversed-phase HPLC method for analysis of different types of Brazilian green propolis extracts (glycolic and ethanolic). The method showed to be selective for the propolis phenolic markers. The analysis of variance and residues demonstrated that the method had significant linear regression, without lack of fit. It was also a precise, accurate and robust method, which was of utmost importance to analyze both glycolic and ethanolic extracts and at different concentrations. Moreover, as these products can display most complex matrices to analyze, a valid HPLC method can also prove to be specific and versatile.
PubDate: 2023-05-19
DOI: 10.1590/s2175-97902023e21972
Issue No: Vol. 59 (2023)
- Development of metformin HCl granules using brown flaxseed mucilage as a
retardant polymer
Authors: Lucas Oliveira Rodrigues, Deborah Quintanilha Falcão, Samanta Mourão
Abstract: Flaxseed (Linum usitatissimum L.) is the seed of a multipurpose plant of pharmaceutical interest, as its mucilage can be used as a natural matrix to develop extended-release dosage forms and potentially replace synthetic polymers. In this study, a 3² factorial design with two replicates of the central point was applied to optimize the development of extended-release granules of metformin HCl. The total fiber content of the mucilage as well as the friability and dissolution of the formulations were evaluated. The lyophilized mucilage presented a high total fiber content (42.63%), which suggests a high efficiency extraction process. Higher concentrations of the mucilage and metformin HCl yielded less friable granules. In addition, lower concentrations of metformin HCl and higher concentrations of the mucilage resulted in slower drug release during the dissolution assays. The release kinetics for most formulations were better represented by the Hixson-Crowell model, while formulations containing a higher concentration of the mucilage were represented by the Korsmeyer-Peppas model. Nonetheless, five formulations showed a longer release than the reference HPMC formulation. More desirable results were obtained with a higher concentration of the mucilage (13-18%) and a lower concentration of metformin (40%).
PubDate: 2023-05-19
DOI: 10.1590/s2175-97902023e22320
Issue No: Vol. 59 (2023)
- 3D-QSARpy
Authors: Priscilla S. S. N. Silverio, Jéssika de Oliveira Viana, Euzébio B. Guimarães
Abstract: Quantitative Structure-Activity Relationship (QSAR) is a computer-aided technology in the field of medicinal chemistry that seeks to clarify the relationships between molecular structures and their biological activities. Such technologies allow for the acceleration of the development of new compounds by reducing the costs of drug design. This work presents 3D-QSARpy, a flexible, user-friendly and robust tool, freely available without registration, to support the generation of QSAR 3D models in an automated way. The user only needs to provide aligned molecular structures and the respective dependent variable. The current version was developed using Python with packages such as scikit-learn and includes various techniques of machine learning for regression. The diverse techniques employed by the tool is a differential compared to known methodologies, such as CoMFA and CoMSIA, because it expands the search space of possible solutions, and in this way increases the chances of obtaining relevant models. Additionally, approaches for select variables (dimension reduction) were implemented in the tool. To evaluate its potentials, experiments were carried out to compare results obtained from the proposed 3D-QSARpy tool with the results from already published works. The results demonstrated that 3D-QSARpy is extremely useful in the field due to its expressive results.
PubDate: 2023-05-19
DOI: 10.1590/s2175-97902023e22373
Issue No: Vol. 59 (2023)
- Neuroprotective potential of the Amazonian fruits Euterpe oleracea Mart.
and Paullinia cupana Kunth
Authors: Gabriel Nóbrega da Costa, Letícia Yoshitome Queiroz, Isaque Nilton dos Santos, Helena Iturvides Cimarosti
Abstract: Acai (Euterpe oleracea Mart.) and guarana (Paullinia cupana Kunth) are native species from the Amazon Forest that in folk medicine are used to treat several diseases due to their anti-inflammatory and antioxidant properties. This review brings together findings from different studies on the potential neuroprotective effects of acai and guarana, highlighting the importance of the conservation and sustainable exploitation of the Amazon Forest. A bibliographic survey in the PubMed database retrieved indexed articles written in English that focused on the effects of acai and guarana in in vitro and in vivo models of neurodegenerative diseases. In general, treatment with either acai or guarana decreased neuroinflammation, increased antioxidant responses, ameliorated depression, and protected cells from neurotoxicity mediated by aggregated proteins. The results from these studies suggest that flavonoids, anthocyanins, and carotenoids found in both acai and guarana have therapeutic potential not only for neurodegenerative diseases, but also for depressive disorders. In addition, acai and guarana show beneficial effects in slowing down the physiological aging process. However, toxicity and efficacy studies are still needed to guide the formulation of herbal medicines from acai and guarana.
PubDate: 2023-05-19
DOI: 10.1590/s2175-97902023e22381
Issue No: Vol. 59 (2023)
- Electrochemical immunosensing of low-density lipoprotein based on sol-gel
encapsulation
Authors: Elton Max Nascimento do Egito, Isaac Aaron Morales Frias, Maria D.L. Oliveira, Cesar Andrade
Abstract: Lipoprotein monitoring is desirable in the management of medical conditions such as atherosclerotic cardiovascular disease and coronary artery disease, in which controlling the concentration of these chylomicrons is crucial. Current clinical methods are complex and present poor reproducibility between laboratories. For these reasons, recent guidelines discard the assessment of low-density lipoprotein cholesterol (LDL-C) as a routine analysis during lipid-lowering therapies. Concerning the importance of monitoring this parameter, the authors present an electrochemical immunosensor constructed from a simple and easy-to-reproduce platform that allows detecting and quantifying LDL nanoparticles directly from human serum samples. The performance of the biosensor was studied by scanning electron microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The biosensing platform displays good stability and linearity between 30 mg dL-1 and 135 mg dL-1 with a detection limit of 20 mg dL-1. The proposed biosensor can be easily employed for monitoring LDL concentration in clinical treatments.
PubDate: 2023-05-15
DOI: 10.1590/s2175-97902023e22430
Issue No: Vol. 59 (2023)
- Preservation of phenolic compounds on dried leaf infusion of Bauhinia
forficata Link
Authors: Débora Vasconcelos Marques, Ana Carolina Duó-Bartolomeu, Marília Elias Gallon, Leonardo Gobbo-Neto, Denise Brentan da Silva, Bianca Waléria Bertoni, Suzelei de Castro França, Ana Maria Soares Pereira, Silvia Helena Taleb Contini
Pages: 97902023e2
Abstract: Bauhinia forficata Link aqueous extract is usually recommended as a phytomedicine to reduce blood glucose levels and its biological activity has been linked to the presence of phenolic compounds from B. forficata preparations. Several drying processes are used in the production of dry herbal extracts, which may influence the chemical composition and efficacy of final herbal medicines. Due to significant chemical changes, defining appropriate drying processes is essential for phytopharmaceutical drug development. In view of this, we analyzed dried B. forficata leaf infusion (BFLI) extracts by HPLC-UV-MSn, followed by molecular networking analysis to evaluate the chemical profiles from dried extracts yielded by freeze-and spray-drying processes. The main metabolites detected included 11 ferulic/isoferulic acid derivatives and 13 glycosylated flavonoids. The qualitative chemical profiles were alike for both drying processes, whereas the relative abundance of some flavonoids was higher using spray-drying. Taken together, our results showed that freeze-and spray-drying preserved the phenolic profile of BFLI and suggested that spray-drying may be the most suitable to obtain its dried products. Along with studying the chemical profiles of dried herbal extracts, evaluating the influence of drying processes on the quality and chemical profiles of final products is pivotal and may benefit future research.
PubDate: 2023-05-15
DOI: 10.1590/s2175-97902023e22076
Issue No: Vol. 59 (2023)
- Development and validation of an analytical method by HPLC-DAD for
determination of caffeine in products based on guarana extracts (Paullinia
cupana)
Authors: Anna Kelly Moura-Silva, Daniel Bonoto Gonçalves, Brayan Jonas Mano-Sousa, Lays Pedrosa Santos, Rafael Serrão da Costa, Frank Andrade, Joaquim M. Duarte-Almeida
Pages: 97902023e2
Abstract: Guarana (Paullinia cupana) is a native plant from the Amazon whose seeds contain a high concentration of caffeine. Aqueous extract of guarana is widely used in the world. In this study, the objective was to develop and validate a High-Performance Liquid Chromatography method for the determination of caffeine in extracts and commercial beverages based on guarana. A sensitive, simple, and viable high performance liquid chromatographic method without the need of an analyte extraction procedure was developed and validated according to Brazilian and international requirements. The method presented high performance, fulfilling Brazilian and international requirements, in addition to allowing product compliance tests. Results confirmed high selectivity and linearity (>0.999) between 5 to 135 ug/mL, with no significant matrix effect. Detection and quantification limits were 0.02 µg/mL and 2 µg/mL, respectively. Precision was less than 4 %, and accuracy varied from 99.9-120 %. Applicability of the method was demonstrated by conducting a limited evaluation in products containing caffeine. Commercial extracts showed quite different caffeine levels, while carbonated drinks follow Brazilian and American recommendations. Our results indicate that the developed method can be used to evaluate the quality of the guarana extract and of products containing caffeine.
PubDate: 2023-05-15
DOI: 10.1590/s2175-97902023e22106
Issue No: Vol. 59 (2023)
- Encapsulation of benznidazole in nanostructured lipid carriers and
increased trypanocidal activity in a resistant Trypanosoma cruzi strain
Authors: Flávia Lidiane Oliveira da Silva, Maria Betânia de Freitas Marques, Maria Irene Yoshida, Wagner da Nova Mussel, João Vinícios Wirbitzki da Silveira, Poliana Ribeiro Barroso, Kelly Cristina Kato, Helen Martins, Guilherme Carneiro
Pages: 97902023e2
Abstract: Chagas disease is a neglected parasitic disease caused by Trypanosoma cruzi, whose treatment has remained unsatisfactory for over 50 years, given that it is limited to two drugs. Benznidazole (BZN) is an efficient antichagasic drug used as the first choice, although its poor water-solubility, irregular oral absorption, low efficacy in the chronic phase, and various associated adverse effects are limiting factors for treatment. Incorporating drugs with such characteristics into nanostructured lipid carriers (NLC) is a promising alternative to overcome these limiting obstacles, enhancing drug efficacy and bioavailability while reducing toxicity. Therefore, this study proposed NLC-BZN formulations in different compositions prepared by hot-melt homogenization followed by ultrasound, and the optimized formulation was characterized by FTIR, DRX, DSC, and thermogravimetry. Biological activities included in vitro membrane toxicity (red blood cells), fibroblast cell cytotoxicity, and trypanocidal activity against epimastigotes of the Colombian strain of T. cruzi. The optimized NLC-BZN had a small size (110 nm), negative zeta potential (-18.0 mV), and high encapsulation (1.64% of drug loading), as shown by infrared spectroscopy, X-ray diffraction, and thermal analysis. The NLC-BZN also promoted lower in vitro membrane toxicity (<3% hemolysis), and 50% cytotoxic concentration (CC50) for NLC-BZN in L929 fibroblast cells (110.7 µg/mL) was twice the value as the free BZN (51.3 µg/mL). Our findings showed that the NLC-BZN had higher trypanocidal activity than free BZN against the epimastigotes of the resistant Colombian strain, and this novel NLC-BZN formulation proved to be a promising tool in treating Chagas disease and considered suitable for oral and parenteral administration.
PubDate: 2023-05-15
DOI: 10.1590/s2175-97902023e22111
Issue No: Vol. 59 (2023)
- Organic osmolyte betaine mitigates the deleterious effects of Diclofenac
in vivo in wistar albino rats
Authors: Mohd. Basheeruddin, Lavanya V., Neesar Ahmed, Shazia Jamal
Pages: e201178 - e201178
Abstract: Diclofenac sodium (DF) is a non-steroidal anti-inflammatory drug (NSAID) that possesses antipyretic, analgesic, antinociceptive and anti-inflammatory activities. Like other NSAIDs, DF is known to be associated with renal, cardiovascular, and gastrointestinal complications. The present study was carried out to evaluate the adverse effects of DF in vivo in wistar albino rats and to assess if oral administration of the organic osmolyte betaine mitigates the adverse effect of DF. Eighteen male Wistar rats were divided into three groups, one group of animals was fed orally with 20 mg/kg of DF once/day, and the other group received a combination of 20 mg/kg of DF and 30 mg/kg of betaine, once/day. Apart from the hematological and biochemical parameters, histopathological changes in the liver, lungs, brain, heart and kidney were also investigated. Histopathological alterations that were found in the liver, kidney, and lungs of DF-treated animals were found to be minimal or absent in DF + betaine-treated animals, as compared to untreated control. The results showed that betaine mitigates the adverse effects associated with DF treatment.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e201178
Issue No: Vol. 59 (2023)
- Antiproliferative effects of 13α/β-steroids on triple-negative
MDA-MB-231 breast cancer cells
Authors: Alexander Scherbakov, Yury Kuznetsov, Margarita Yastrebova, Alvina Khamidullina, Danila Sorokin , Maria Tserfas, Inna Levina
Pages: e22540 - e22540
Abstract: This study aimed to investigate the activities of novel 20(R)-3,20-dihydroxy-19-norpregn-1,3,5(10)-trienes (kuz7 and kuz8b) of natural 13β- and epimeric 13α-series against triple-negative MDA-MB-231 breast cancer cells. High antiproliferative activity of synthesized compounds kuz8b and kuz7 against MDA-MB-231 triple-negative cancer cells was revealed. The steroid kuz7 of natural 13β-configuration was more active against MDA-MB-231 cells than the 13α-steroid kuz8b. Cell cycle analysis revealed common patterns for the action of both tested compounds. The number of cells in the subG1 phase increased in a dose-dependent manner, indicating induction of apoptosis, which was also verified by PARP cleavage. In contrast, the number of cells in the G0/G1 phase decreases with increasing compound concentration. Steroid kuz7 at micromolar concentrations reduced the expression of GLUT1, a glucose transporter. High efficacy of the combination of kuz7 with biguanide metformin was shown, and synergistic effects on MDA-MB-231 cell growth and expression of the anti-apoptotic protein Bcl-2 were revealed. According to the obtained results, including the high activity of kuz7 against triple-negative cancer cells, the detected induction of apoptosis, and the decrease in GLUT1 expression, 13β-steroid kuz7 is of interest for further preclinical studies both alone and in combination with the metabolic drug metformin.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e22540
Issue No: Vol. 59 (2023)
- Health education can save the environment from medicine residues
Authors: Giulia de Souza Castro, Estael Luzia Coelho da Cruz-Cazarim, Marcelo Silva Silvério, Alessandra Esthér de Mendonça, Maurílio de Souza Cazarim
Pages: e21525 - e21525
Abstract: The incorrect disposal of medicines and their environmental impact has been related to the health medicalization and the improper use of medication by society. In this sense, it is very important to know the profile of drug disposal for foster health policies. The aim was to identify the profile of disposal of medicines by the population, including the cost perspective. This is an inquiry descriptive study that began in September 2019. Medicine disposal health education program was carried out over six months in two University pharmacies. A questionnaire for sociodemographic and discarded medicines data collection was applied. Logistic regression analysis for variables association of correct disposal and the chi-square and t-student analysis for comparison between disposal programs were performed for a level of 5% and test power of 80%. Medicines weighed 23.3 kg and 28.5 kg, with the cost variation from US$ 13.5 to US$ 16.1 until the final treatment. The correct disposal was strongly associated with the disposal reason (p=0.013), source of information (p=0.006), prescription (p=0.03), form of use (p=0.01), acquisition source (p=0.001), cost with medication (p=0.0001), education (p=0.028) and age (p=0.05). The correct medicine disposal was associated with important features of the community related to education health.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e21525
Issue No: Vol. 59 (2023)
- Optimization of the ellagic acid synthesis process at the bioreactor level
using non-conventional yeasts
Authors: Rafael Madrigal-Chávez, Kristal Ruíz-Pompa, Anahí Márquez-López , Dora Cecilia Valencia Flores, Ma. Del Carmen Chávez-Parga, Juan Carlos González-Hernández
Pages: e21508 - e21508
Abstract: Ellagic acid (EA) is a phenolic biomolecule. For its biosynthesis, a source of ellagitannins is required, such as strawberries and yeasts, as precursors of the tannase and β-glucosidase enzymes responsible for hydrolysis of ellagitannins. Two experimental mixture designs were applied., varying the yeast concentration and the number of ellagitannins in the culture medium, evaluating the enzymatic activity and ellagic acid biosynthesis. Aiming to find the optimal compositions of the non-conventional yeasts assessed in the research to biosynthesize ellagic acid feasibly and efficiently using a response surface performing the statistical analysis in the StatGraphics® program for obtaining a higher yield and optimizing the ellagic acid synthesis process, the results indicate that the strains Candida parapsilosis ITM LB33 and Debaryomyces hansenii ISA 1510 have a positive effect on the synthesis of ellagic acid, since as its concentration increases in the mixture the concentration of ellagic acid in the medium also increases; on the other hand, the addition of Candida utilis ITM LB02 causes a negative effect, resulting in the compositions of 0.516876, 0.483124 and 2.58687E-9 respectively, for a treatment under the same conditions, an optimal value of ellagic acid production would be obtained. With an approximate value of 7.33036 mg/mL.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e21508
Issue No: Vol. 59 (2023)
- Effect of pancreatin on acute pancreatitis resulting from L-arginine
administration in mice, a morphohistopathological and biochemical study
Authors: Rahmat Allah Fatahian Dehkordi, Iraj Karimi, Behnaz Karimi, Reyhaneh Ghasemi Eshkaftaki, Reza Abtahi, Hanie Mohammadi
Pages: e21494 - e21494
Abstract: Acute pancreatitis (AP) is a life-unpleasant situation with contradictory and inadequate treatments. In this regard, the present study evaluated the effect of the possible pretreatment of lipase-pancreatin on L-arginine-induced AP. Forty adult mice were selected and divided into five groups: I) control group, II and III) AP groups (i.p.) receiving L-arginine of 2×300 and 2×400 mg/100 g body weight (b.w.), IV) AP (2×300 L-arginine) group + pancreatin (mice were i.p. injected by 350 U-lipase), and V) AP (2×400 L-arginine) group + pancreatin (mice were i.p. injected by 350 U-lipase). All AP groups displayed a significant increase in serum levels of ALT, AST, TBARS, and TNF-alpha compared to the control group. Moreover, pancreatic tissue edema, inflammation, and vacuolization of acinar cells were significantly higher in the untreated L-arginine group compared to the control and pancreatin groups. Conversely, the diameter of pancreatic islets significantly declined after induction of pancreatitis compared with control and pancreatin groups. Pancreatin treatment can be used in pancreatic dysfunction, however, this medicine showed no protective effect against L-arginine-induced AP in the mouse model.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e21494
Issue No: Vol. 59 (2023)
- Solid-state properties of pink clay from Jequitinhonha Valley in Brazil
for pre-formulation study
Authors: Maria Betânia de Freitas Marques, Osmar Patrício Almeida, Bárbara Caroline Rodrigues Araújo, José Domingos Ardisson, Rita de Cássia de Oliveira Sebastião, Flávia Lidiane Oliveira da Silva, Wagner da Nova Mussel, Maria Irene Yoshida, Guilherme Carneiro
Pages: e21460 - e21460
Abstract: Clay minerals are still widely used in pharmaceutical products for human health and cosmetic purposes. Pre-formulation studies were conducted to identify solid-state properties of pink clay, a sample from Diamantina, Brazil. Among the solid properties to be analyzed, we have selected type identification, iron phases, crystallinity, powder flow characteristics, thermal behavior, and non-isothermal phase transition kinetics. The pink clay is composed of (1:1) clay type and kaolinite as the main component. The Mössbauer spectrum of pink clay shows Fe3+(α-Fe2O3) hematite, Fe2+, and Fe3+ with large Δ/2ξq of about 2.80 and 2.69 mm.s-1 respectively, related to iron silicates, most likely pyroxene, and a superparamagnetic Fe3+. Pink clay exhibits poor flow properties. The thermal behavior indicates a phase-transition between 400 - 600 ºC associated with the dehydroxylation of the pink clay system requiring ~300 kJ mol-1, being constant until the process reaches a conversion of ~50% when the energy is enhanced to ~530 kJ mol-1, concluding the whole dehydroxylation process (α=80%). Solid-state properties and characteristics found for the pink clay must be considered for the proper design of formulations. This type of clay shows unique pharmaceutical properties that can be favorably exploited by the cosmetic industry.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e21460
Issue No: Vol. 59 (2023)
- Levetiracetam plus Oxcarbazepine Combination Treatment Downregulates Serum
Multidrug Resistance Protein 1 Levels and Upregulates Neuropeptide Y
Levels in Children with Epilepsy
Authors: Jiahong Wang
Pages: e21414 - e21414
Abstract: The aim of the present study was to investigate the usefulness of multidrug resistance protein 1 (MDR1) and neuropeptide Y (NPY) levels in predicting the efficacy of levetiracetam (LEV) plus oxcarbazepine (OXC) treatment administered to children with epilepsy and to determine their prognosis. Overall, 193 children with epilepsy admitted to the hospital were enrolled and randomly divided into two groups according to different treatment methods: group A (n = 106, treated with LEV plus OXC combination) and group B (n = 87, treated with OXC only). After treatment, compared with group B, group A exhibited a remarkably higher total effective rate and a significantly lower total adverse reaction rate. Areas under the curve for MDR1 and NPY for predicting ineffective treatment were 0.867 and 0.834, whereas those for predicting epilepsy recurrence were 0.916 and 0.829, respectively. Electroencephalography abnormalities, intracranial hemorrhage, neonatal convulsion, premature delivery, and MDR1 and NPY levels were independent risk factors for poor prognosis in children with epilepsy. Serum MDR1 and NPY levels exhibited a high predictive value for early epilepsy diagnosis, treatment efficacy assessment, and prognostication in children with epilepsy treated with LEV plus OXC combination.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e21414
Issue No: Vol. 59 (2023)
- Prediction of the Impact of CYP2C19 Polymorphism on Drug-Drug Interaction
between Voriconazole and Tacrolimus Using Physiologically-Based
Pharmacokinetic Modelling
Authors: Zhiping Jin, Miao Yan, Size Li, Baoqing Wang, Qing Xu, Wei Wu, Xiaoyu Li, Qianzhou Lv, Xiaoqiang Xiang
Pages: e21343 - e21343
Abstract: Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e21343
Issue No: Vol. 59 (2023)
- Dill seed oil as a possible contraceptive agent
Authors: Gönül Ulus, Melih Zeytinoğlu, Mine Kürkçüoğlu, Kemal Hüsnü Can Başer, Koparal Ayşe Tansu
Pages: e20060 - e20060
Abstract: Dill (Anethum graveolens L.) essential oil is wide spread in the food, beverage and pharmaceutical sectors. Dill is a member of the Apiaceae (Umbelliferae) family. It has the following biological activities: antioxidant, antifungal, antibacterial, antimicrobial, antihyperlipidemic, antihypercholesterolemic, antispasmodic, antiproliferative and anti-inflammatory. Aqueous extract of dill seed has reported effects on sex hormones and infertility potential. Moreover, boiled dill seed has an impact on reducing labor duration in giving birth. Implantation and placentation are necessary for a healthy pregnancy in the early stages. Angiogenesis is responsible for these essential processes. This study aimed to investigate dill seed oil’s cytotoxic and antiangiogenic effects on rat adipose tissue endothelial cells (RATECs). Dill seed oil showed dose-dependent cytotoxicity on RATECs. It disrupted endothelial tube formation and depolymerized F-actin stress fibers. According to this study, depolymerization of F-actin stress fiber by dill seed oil could inhibit angiogenesis by suppressing endothelial cell proliferation, tube formation and motility. In other words, dill seed oil can be a new anti-angiogenic agent and a novel contraceptive.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e20060
Issue No: Vol. 59 (2023)
- Preformulation screening of lipids using solubility parameter concept in
conjunction with experimental research to develop ceftriaxone loaded
nanostructured lipid carriers
Authors: Swarupanjali Padhi, Rupa Mazumder, Shradha Bisth
Pages: e21308 - e21308
Abstract: Development of ceftriaxone loaded nanostructured lipid carriers to increase permeability of ceftriaxone across uninflamed meninges after parenteral administration. Lipids were selected by theoretical and experimental techniques and optimization of NLCs done by response surface methodology using Box-Behnken design. The Δδt for glyceryl monostearate and Capryol90 were 4.39 and 2.92 respectively. The drug had maximum solubility of 0.175% (w/w) in glycerol monostearate and 2.56g of Capryol90 dissolved 10mg of drug. The binary mixture consisted of glyceryl monostearate and Capryol90 in a ratio of 70:30. The optimized NLCs particle size was 130.54nm, polydispersity index 0.28, % entrapment efficiency 44.32%, zeta potential -29.05mV, and % drug loading 8.10%. In vitro permeability of ceftriaxone loaded NLCs was 5.06x10-6 cm/s; evidently, the NLCs pervaded through uninflamed meninges, which, was further confirmed from in vivo biodistribution studies. The ratio of drug concentration between brain and plasma for ceftriaxone loaded NLCs was 0.29 and that for ceftriaxone solution was 0.02. With 44.32% entrapment of the drug in NLCs the biodistribution of ceftriaxone was enhanced 7.9 times compared with that of ceftriaxone solution. DSC and XRD studies revealed formation of imperfect crystalline NLCs. NLCs improved permeability of ceftriaxone through uninflamed meninges resulting in better management of CNS infections.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e21308
Issue No: Vol. 59 (2023)
- Development of microparticles and microparticulated tablets containing
piperine
Authors: Aline Colling Schneider, Carlos Eduardo de Souza Brener, Natália de Freitas Daudt, Letícia Cruz, Cristiane da Silva
Pages: e21265 - e21265
Abstract: Piper nigrum (black pepper) is used in Indian traditional medicine and its main alkaloid, Piperine (PIP), presents antioxidant, antitumor and neuroprotective pharmacological properties. This substance is insoluble in aqueous media and can irritate the gastrointestinal tract. Aiming to avoid these inconvenient characteristics and enable PIP oral administration, this study suggested the PIP microencapsulation through the emulsion-solvent evaporation method and the preparation of microparticulated tablets by direct compression. An UV-spectroscopy method was validated to quantify PIP. Microparticles and microparticulated tablets were successfully obtained and the microparticles exhibited excellent flow. The scanning electron microscopy images showed that PIP microparticles were intact after compression. The in vitro release showed a controlled release of PIP from microparticles and PIP microparticles from tablets in comparison to PIP and PIP tablets. The release profiles of PIP microparticles and the microparticulated tablets were similar. Therefore, tablets containing PIP microparticles are promising multiparticulated dosage forms because a tablet allows microparticles administration and the intact ones promote a controlled release, decreasing its irritating potential on the mucosa.
PubDate: 2023-05-08
Issue No: Vol. 59 (2023)
- Development of microparticles and microparticulated tablets containing
piperine
Authors: Aline Colling Schneider, Carlos Eduardo de Souza Brener, Natália de Freitas Daudt, Letícia Cruz, Cristiane da Silva
Pages: e21265 - e21265
Abstract: Piper nigrum (black pepper) is used in Indian traditional medicine and its main alkaloid, Piperine (PIP), presents antioxidant, antitumor and neuroprotective pharmacological properties. This substance is insoluble in aqueous media and can irritate the gastrointestinal tract. Aiming to avoid these inconvenient characteristics and enable PIP oral administration, this study suggested the PIP microencapsulation through the emulsion-solvent evaporation method and the preparation of microparticulated tablets by direct compression. An UV-spectroscopy method was validated to quantify PIP. Microparticles and microparticulated tablets were successfully obtained and the microparticles exhibited excellent flow. The scanning electron microscopy images showed that PIP microparticles were intact after compression. The in vitro release showed a controlled release of PIP from microparticles and PIP microparticles from tablets in comparison to PIP and PIP tablets. The release profiles of PIP microparticles and the microparticulated tablets were similar. Therefore, tablets containing PIP microparticles are promising multiparticulated dosage forms because a tablet allows microparticles administration and the intact ones promote a controlled release, decreasing its irritating potential on the mucosa.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e21265
Issue No: Vol. 59 (2023)
- The preventive effect of exogenous adenosine triphosphate on
methanol-induced cardiotoxicity in rats
Authors: Resit Coskun, Aziz Inan Celik, Muharrem Said COSGUN, Renad Mammadov
Pages: e21220 - e21220
Abstract: Exposure to methanol can cause serious consequences such as permanent visual disturbances and death. The heart tissue is highly vulnerable to ATP deficiency. Our study aimed to investigate whether exogenous ATP administration may alleviate methanol-induced ATP deficiency and subsequent oxidative damage in rat heart tissue. A total of 30 rats were divided into equal five groups; Healthy Group (HG), Methotrexate (MXG), Methanol (MeOH), Methotrexate+Methanol (MXM), and Methotrexate+Methanol+ATP (MMA) groups. We inhibited tetrahydrofolate synthesis by methotrexate to induce methanol toxicity. Methotrexate was administered to MXG, MXM, and MMA group animals for seven days with a catheter directly to the stomach at a 0,3 mg/kg dose per day. At the end of this period, % 20 methanol at a dose of 3 g/kg was administered to MeOH, MMA and MXM group animals. Immediately after methanol application, MMA group animals were injected with ATP at a 4 mg/kg dose intraperitoneally. Blood samples and heart tissues were used for biochemical analysis and histopathological examination. Co-exposure to methanol and methotrexate substantially exacerbated cardiac damage, indicating the potent cardiotoxic effects of methanol. However, the administration of exogenous ATP to MMA group animals brought biochemical oxidative damage parameters and histopathological findings closer to HG.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e21220
Issue No: Vol. 59 (2023)
- In vitro antibacterial-antibiofilm effect of Hypericum atomarium Boiss and
chemical composition
Authors: Ebru Önem, Ayşe Gül Özaydın, Hasan Cumhur Sarısu
Pages: e20412 - e20412
Abstract: Treatment with plant is considered an effective option against increased antibiotic resistance. In this study antibiofilm activity of methanol (CH3OH), chloroform (CHCl3), ethyl acetate (EtOAc) and water (H2O) extracts of Hypericum atomarium Boiss. which is member of Hypericum genus was evaluated in Pseudomonas aeruginosa PAO1 and antibacterial performance against Gram (+) and Gram (-) strains and also bioactive compounds of extract were analysed using by HPLC and GC-MS. According to antibacterial activity test results the extracts were effective all Gram (+) bacteria and Gram (-) Chromobacterium violaceum (MICs ranging from 0.42 μg/ml to 4.3 mg). Inhibition effect of biofilm formation was found to be different rate in extracts (methanol-63%, chloroform-52%). The major flavonoids were detected (−)-epicatechin (2388.93 μg/ml) and (+)-catechin (788.94 μg/ml). The main phenolic acids were appeared as caffeic acid 277.34 μg/ml and chlorogenic acid 261.79 μg/ml. And according to GC results α-pinene was found main compound for three solvent extracts methanol, chloroform and ethyl acetate 67.05, 62.69, 49.28% rate respectively.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e20412
Issue No: Vol. 59 (2023)
- Ameliorating effects of ethanol extract of root bark of Salacia nitida on
blood electrolyte and renal perturbations in Plasmodium berghei-infected
mice
Authors: Barine Innocent Nwiloh, Augustine Amadikwa Uwakwe
Pages: e20229 - e20229
Abstract: Malaria, a disease of public health concern is a known cause of kidney failure, and dependence on herbal medicines for its treatment is increasing due to the high cost of drugs. So this study is designed to evaluate the ameliorating effect of ethanol extract from Salacia nitida root bark on electrolyte and renal perturbations in Plasmodium berghei-infected mice. Thirty malariainfected mice divided into five groups of six mice each and another group of six uninfected mice were used for the study. 280, 430, and 580 mg/kg of extract were given to infected mice in groups B, C, and D, 4 mg/kg of artesunate given to group E mice, and 4 ml/kg of physiological saline given to group A and uninfected group F mice for five days. Serum Na+, K+, HCO3, Cl-, TB, urea, creatinine, BUN concentrations, and BUN/creatinine ratio were determined using standard methods. Results showed significant increases (p < 0.05) in Na+, K+, and HCO3 and decreases in Cl-, TB, urea, creatinine, BUN, and BUN/creatinine ratio in the infected treated mice in groups B - E. This study showed that ethanol extract of S. nitida root bark is efficient in the treatment of renal disorders and blood electrolyte perturbations.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e20229
Issue No: Vol. 59 (2023)
- Bioactivity evaluation of least explored traditionally acclaimed
medicinally potent herb Nanorrhinum ramosissimum(Wall.) Betsche
Authors: Jyotsna Sharma, Savita Sharma, Anuja Koul, Raju Shankarayan, Sharada Mallubhotla
Pages: e19334 - e19334
Abstract: Present study analysed the therapeutic potential of traditionally acclaimed medicinal herb Nanorrhinum ramosissimum, using plant parts extracted with different solvents (10 mg/mL). Shoot extracts exhibited comparatively better antimicrobial properties, in comparison to root extracts. Total phenolic content was estimated, to ascertain its dependency on antioxidant properties of plant extracts. Antioxidant assay revealed promising results in comparison to IC50 value of standard ascorbic acid (52.2±0.07 µg/mL), for methanolic extracts of shoot (61.07±0.53 µg/mL and 64.33±0.33 µg/mL) and root (76.705±0.12 µg/mL and 89.73±0.28 µg/ mL) for in vivo and in vitro regenerants respectively. Correlation coefficient R2 values ranged between 0.90-0.95, indicating a positive correlation between phenolic contents and antioxidant activity. Plant extracts were also able to inhibit DNA oxidative damage again indicating their antioxidative potential. Antidiabetic potential was confirmed by alpha amylase inhibition assay where shoot methanolic extracts (invivo, in vitro) exhibited the best IC50 values (54.42±0.16 µg/mL, 66.09±0.12 µg/mL) in comparison to standard metformin (41.92±0.08 µg/mL). Ethanolic extracts of roots (in vitro, invivo) exhibited the relative IC50 values (88.97±0.32µg/mL,96.63±0.44 µg/mL) indicating that shoot parts had a better alpha amylase inhibition property; thus proving the herb’s bioactive potential and its prospective therapeutic source for curing various ailments.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e19334
Issue No: Vol. 59 (2023)
- Anti-hyperglycemic fraction from Alternanthera sessilis L. leaves gets
elucidated following bioassay-guided isolation and mass spectrometry
Authors: Richelle Ann Mallapre Manalo, fmheralde1@up.edu.ph
Pages: e21283 - e21283
Abstract: The anecdotal use of Alternanthera sessilis L. as a relief for diabetes has been known in the Philippines for generations, and antidiabetic activity of similar varieties in other countries is likewise documented. However, the compounds responsible for this activity remain unclear. This study aims to isolate the anti-hyperglycemic fraction of local A. sessilis leaves and identify the compounds in this fraction. Methanol extract of A. sessilis leaves and its hexane, ethyl acetate (ASE), and water fractions were administered to alloxan-induced diabetic mice. ASE (250mg/kg) had the highest anti-hyperglycemic activity at 6-h post-treatment (25.81%±12.72%), with almost similar blood glucose reduction rate as metformin (30.13±3.75%, p=0.767). Repeated fractionation employing chromatographic separation techniques followed by in vivo anti-hyperglycemic assay yielded partially purified subfractions. A. sessilis ethyl acetate subfraction 4-2 (100mg/kg) displayed remarkable suppression of blood glucose rise in diabetic mice at 6-h post-treatment (26.45±3.75%, p<0.0001), with comparable activity with metformin (100mg/kg, 27.87±5.65%, p=0.652). Liquid chromatography/mass spectrometry showed eight distinct peaks, with four peaks annotated via the Traditional Chinese Medicine library and custom library for A. sessilis. Among these, luteolin, apigenin, ononin, and sophorabioside were identified as putative compounds responsible for the anti-hyperglycemic activity. This result provided basis for the reported anecdotal claims and potential utility of the local variety of A. sessilis leaves as sources of anti-hyperglycemic agents.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e21283
Issue No: Vol. 59 (2023)
- Biological screening of herbal extracts and essential oil from
Plectranthus species
Authors: Simony Carvalho Mendonça, Smail Aazza, Alexandre Alves de Carvalho, Diogo Mendes da Silva, Nelma de Mello Silva Oliveira, José Eduardo Brasil Pinto Pinto, Suzan Kelly Vilela Bertolucci
Pages: e21117 - e21117
Abstract: The phenolic compound content, the antioxidant and α-amylase inhibition potentials of different extracts of the Plectranthus amboinicus, P. barbatus and P. ornatus were evaluated. We also evaluated the influence of plant growth and harvest time on the chemical composition of the essential oil (EO) of P. amboinicus, its antioxidant and anti-Candida activities and the α-amylase and lipoxygenase inhibitions. The turbo-extract of P. barbatus showed the greatest phenolic compound content and antioxidant activity. No α-amylase inhibition activity was observed in the analyzed extracts, but the turbo-extraction and refluxing extracts possessed high antioxidant activities. Protected cultivation and morning harvest conditions gave the best antioxidant activities, which was associated to the highest carvacrol content. P. amboinicus EO antioxidant activity could contribute to the reduction of oxidative stress in diabetes. Causal Candida strains of diabetic foot ulcers showed sensitivity to P. amboinicus EO. C. albicans and C. dubliniensis were the most sensitive of the selected Candida strains. Turbo-extracts or refluxing of the three species extracts and the EO of P. amboinicus should be considered as a potential candidate for the management the complications of type 2 diabetes.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e21117
Issue No: Vol. 59 (2023)
- Development and validation of liquid chromatography-tandem mass
spectrometry method to quantify dasatinib in plasma and its application to
a pharmacokinetic study
Authors: Edlaine Rijo Costa, Thales Nascimento Castro, Cassiano Felippe Gonçalves-de-Albuquerque, Hugo Caire de Castro Faria Neto, José Carlos Saraiva Gonçalves, Rita de Cássia Elias Estrela *
Pages: e21415 - e21415
Abstract: Dasatinib, a potent oral multi-targeted kinase inhibitor against Src and Bcr-Abl, can decrease inflammatory response in sepsis. A simple and cost-effective method for determination of an effective dose dasatinib was established. This method was validated in human plasma, with the aim of reducing the number of animals used, thus, avoiding ethical problems. Dasatinib and internal standard lopinavir were extracted from 180 uL of plasma using liquid-liquid extraction with methyl tert-butil ether, followed by liquid chromatography coupled to triple quadrupole mass spectrometry in multiple reaction monitoring mode. For the pharmacokinetic study, 1 mg/kg of dasatinib was administered to mice with and without sepsis. The method was linear over the concentration range of 1-98 ng/mL for DAS in mice and human plasma, with r2>0.99 and presented intra- and interday precision within the range of 2.3 - 6.2 and 4.3 - 7.0%, respectively. Further intra- and interday accuracy was within the range of 88.2 - 105.8 and 90.6 - 101.7%, respectively. The mice with sepsis showed AUC0-t = 2076.06 h*ng/mL and Cmax =102.73 ng/mL and mice without sepsis presented AUC0-t = 2128.46 h*ng/mL. Cmax = 164.5 ng/mL. The described analytical method was successfully employed in pharmacokinetic study of DAS in mice.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e21415
Issue No: Vol. 59 (2023)
- Cytotoxicity evaluation of haloperidol, clozapine and a new molecule with
antipsychotic potential, PT-31, in NIH-3T3 cells
Authors: Carlos Henrique Thomazi, Alana Witt Hansen, Juliana Machado Kayser, Marina Griebeler Moreira, Marina Galdino da Rocha Pitta, Ivan da Rocha Pitta, Ana Luiza Ziulkoski, Andresa Heemann Betti
Pages: e21738 - e21738
Abstract: Schizophrenia is an illness that affects 26 million people worldwide. However, conventional antipsychotics present side effects and toxicity, highlighting the need for new antipsychotics. We aimed to evaluate the cytotoxicity of haloperidol (HAL), clozapine (CLO), and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells. The neutral red uptake assay and the MTT assay were performed to evaluate cell viability and mitochondrial activity, morphological changes were assessed, and intracellular reactive oxygen species (ROS) detection was performed. HAL and CLO (0.1 μM) showed a decrease in cell viability in the neutral red uptake assay and in the MTT assay. In addition, cell detachment, content decrease, rounding and cell death were also observed at 0.1 μM for both antipsychotics. An increase in ROS was observed for HAL (0.001, 0.01 and 1 μM) and CLO (0.01 and 1 μM). PT-31 did not alter cell viability in any of the assays, although it increased ROS at 0.01 and 1 μM. HAL and CLO present cytotoxicity at 0.1 μM, possibly through apoptosis and necrosis. In contrast, PT-31 does not present cytotoxicity to NIH-3T3 cells. Further studies must be performed for a better understanding of these mechanisms and the potential risk of conventional antipsychotics.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e21738
Issue No: Vol. 59 (2023)
- Study of the potential toxicity of adrenaline to neurons, using the
SH-SY5Y human cellular model
Authors: Vera Marisa Costa , Félix Carvalho
Pages: e20467 - e20467
Abstract: Prolonged overexposure to catecholamines causes toxicity, usually credited to continuous adrenoceptor stimulation, autoxidation, and the formation of reactive pro-oxidant species. Non-differentiated SH-SY5Y cells were used to study the possible contribution of oxidative stress in adrenaline (ADR)-induced neurotoxicity, as a model to predict the toxicity of this catecholamine to peripheral nerves. Cells were exposed to several concentrations of ADR (0.1, 0.25, 0.5 and 1mM) and two cytotoxicity assays [lactate dehydrogenase (LDH) release and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction] were performed at several time-points (24, 48, and 96h). The cytotoxicity of ADR was concentration- and time-dependent in both assays, since the lowest concentration tested (0.1mM) also caused significant cytotoxicity at 96h. N-acetyl-cysteine (1mM), a precursor of glutathione synthesis, prevented ADR-induced toxicity elicited by 0.5mM and 0.25mM ADR following a 96-h exposure, while the antioxidant Tiron (100µM) was non-protective. In conclusion, ADR led to mitochondrial distress and ultimately cell death in non-differentiated SH-SY5Y cells, possibly because of ADR oxidation products. The involvement of such processes in the catecholamine-induced peripheral neuropathy requires further analysis.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e20467
Issue No: Vol. 59 (2023)
- Oral and nasal vaccination
Authors: Natália F. Paiva, Fabiana Vicentini
Pages: e21769 - e21769
Abstract: Currently, mucosal vaccine administration has stood out as an easier and non-invasive application method. It can also be used to induce local and systemic immune responses. In the COVID-19 pandemic context, nasal and oral vaccines have been developed based on different technological platforms. This review addressed relevant aspects of mucosal vaccine administration, with emphasis on oral and nasal vaccinations, in addition to the importance of using nanotechnology-based delivery systems to enable these strategies.
PubDate: 2023-05-08
DOI: 10.1590/s2175-97902023e21769
Issue No: Vol. 59 (2023)
- Cell phenotypes as activity biomarkers in patients with Systemic Lupus
Erythematosus
Authors: Cristina de Mello Gomide Loures, Tânia Mara Pinto Dabés Guimarães, Karine Silveste Ferreira, Marcos Vinicius Ferreira Silva, Luan Carlos Vieira Alves, Fernanda Freire Campos Nunes, Renato Vargas Consoli, Cláudia Lopes Santoro Neiva, Paulo Madureira de Pádua, Luara Isabela dos Santos, Josimar Dornelas Moreira, Vicente de Paulo Coelho Peixoto de Toledo, Maria das Graças Carvalho
Pages: e20052 - e20052
Abstract: The pathogenesis of systemic lupus erythematosus (SLE) is complex. Few studies in Brazilian population have addressed cell phenotypes associated with immunological responses and their associations with SLE activity. The aim of this study is to investigate cell phenotypes associated to SLE diagnosis, treatment and activity. Twenty-eight SLE female patients (17 inactive, 11 active) and 10 healthy women were included in this study. Markers of natural killer (Nk), T and B cells in peripheral blood were evaluated by flow cytometry. Nkt cells were decreased only in SLE active patients. Activated CD4+, regulatory T FoxP3+ and B cells were decreased in both active and inactive SLE patients, compared to control group. The data corroborate the disruption of immune regulatory response in SLE patients and suggest phenotipic changes as possible biomarkers of SLE activity.
PubDate: 2023-04-28
DOI: 10.1590/s2175-97902023e20052
Issue No: Vol. 59 (2023)
- nfluence of solvent choice and operating conditions on Chlorzoxazone
crystal shape and size
Authors: Dhayananth Natarajan, Kalaichelvi Ponnusamy, Radhakrishnan Thota Karunakaran, Karthika Shanmugam
Pages: e20918 - e20918
Abstract: Solubility of pharmaceutical drugs in organic solvents is one of the important parameters to understand the equilibrium concentration of solute-solvent, which helps optimize and design crystallization conditions to obtain the desired product crystals. In the present study, Chlorzoxazone (CHZ) is used as a model pharmaceutical compound to investigate the equilibrium solubility, the influence of solvent and the operating conditions on the shape, and the size distribution. The solubility of CHZ is determined in organic solvents like Isopropanol, Ethanol, and 2-Ethoxyethylacetate, Ethylacetate and Ethyllactate using shake flask method from -5ºC to 60ºC. The solubility of CHZ in these solvents shows an increasing trend as the temperature increases in the following order: ethyllactate + water (0.5+0.5) < ethylacetate < isopropanol < ethanol < 2-ethoxyethylacetate < ethyllactate + water (0.75+0.25). The solvents, isopropanol, ethanol, and ethyl lactate, produce needle-shaped crystals, while 2-ethoxyethylacetate and ethyl acetate tend to produce plate shaped crystals. CHZ crystals obtained from 2-ethoxyethylacetate tend to have plate shaped crystals with a lower aspect ratio and are selected for batch cooling crystallization experiments performed at different cooling rates, and agitation. It is found that the agitation at 300 rpm and the cooling rate 0.2ºC/min produce more uniform crystal size distribution.
PubDate: 2023-04-28
DOI: 10.1590/s2175-97902023e20918
Issue No: Vol. 59 (2023)
- A retrospective analysis to estimate trough concentrations of teicoplanin
in patients with suspected or documented Gram-positive infections
Authors: Luo Yi-Fan, Wang Yi-Dan, Ren Li-Xiang, Chu Yang
Pages: e21077 - e21077
Abstract: Teicoplanin is a glycopeptide antibiotic commonly used to treat Gram-positive bacterial infections in the clinic. The aim of this study was to provide a therapeutic reference for the clinical application and dosage regimen adjustment of teicoplanin by identifying factors associated with its plasma trough concentration (Ctrough). A retrospective study was performed on patients with suspected or documented Gram-positive infections who were hospitalized from November 2017 to January 2020 and treated with teicoplanin while undergoing routine therapeutic drug monitoring (TDM). A total of 112 Ctrough trough measurements were obtained from 72 patients were included in this study. SPSS software was used for correlation analysis and receiver operator characteristic curve (ROC) analysis. The Ctrough for teicoplanin showed statistically significant relationships (P<0.05) with PLT, Scr, CLcr, eGFR, BUN and Cys-C. ROC curve analysis revealed that CLcr and eGFR were more sensitive and specific for Ctrough compared to the other factors. These findings should be considered in the clinical application of teicoplanin and for its dosage adjustment.
PubDate: 2023-04-28
DOI: 10.1590/s2175-97902023e21077
Issue No: Vol. 59 (2023)
- Compounded drugs as an alternative to the therapeutical gaps of inborn
errors of metabolism
Authors: Adrielle da Silva Fachini, Lorena Freitas Barros Malaquias, Luma de Lira Nogueira, Ludmila Alvim Gomes Pinho Giacone, Noemia Urruth Leão Tavares, Maria Teresinha de Oliveira Cardoso, Guilherme Martins Gelfuso, Dayde Lane Mendonça da Silva, Rafael Santos Santana
Pages: e21109 - e21109
Abstract: Inborn errors of metabolism are rare disorders with few therapeutic options for their treatments, which can make patients suffer with complications. Therefore, compounded drugs might be a promising option given that they have the ability of meeting the patient’s specific needs, (i) identification of the main drugs described in the literature; (ii) proposal of compounding systems and (iii) calculation of the budgetary addition for the inclusion of these drugs into the Brazilian Unified Health System. The research conducted a literature review and used management data as well as data obtained from official Federal District government websites. The study identified 31 drugs for the treatment of inborn errors of metabolism. Fifty eight percent (58%) (18) of the medicines had their current demand identified, which are currently unmet by the local Health System. The estimated budget for the production of compounded drugs was of R$363,16.98 per year for approximately 300 patients. This estimated cost represents a budgetary addition of only 0.17% from the total of expenditures planned for drug acquirement. There is a therapeutic gap for inborn errors of metabolism and compounding pharmacies show potential in ensuring access to medicine therapy with a low-cost investment.
PubDate: 2023-04-28
DOI: 10.1590/s2175-97902023e21109
Issue No: Vol. 59 (2023)
- The Impact of Cultural Factors, The Level of Health Education Received by
the Caregivers, and Stigma on Asthma Treatment among Children in Southern
Jordan
Authors: Fatima Mahmoud Al-Tarawneh, Diala Abdul Kareem AlTwalbeh, Wesam khalid Al-Amarat
Pages: e21115 - e21115
Abstract: For asthma treatment in children, caregivers need good knowledge and attitudes regarding the disease and its treatment. This study aimed to determine the impact of cultural factors, the level of health education provided to patients and their families, as well as the impact of stigmatization on the treatment awareness of children with asthma in southern Jordan. A validated questionnaire was used to collect data from a sample of ninety-seven caregivers selected from three hospitals in southern Jordan. Open ended questions were answered after demonstrating the inhaler technique in and evaluated according to the instructions of the National Asthma Education and Prevention Program (NAEPP, 2013). The result revealed moderate knowledge of asthma with a mean score of (22.36/32), as well as moderate knowledge of asthma treatment (24.26/40). A high mean was found for the impact of cultural and environmental factors (22.93/28), whereas low impact was found for stigma with a mean value of (4.73/12). Therefore, to improve future asthma management, additional efforts are required to educate caregivers and improve their asthma awareness and rectify any falsehoods regarding asthma medications by health care providers.
PubDate: 2023-04-28
DOI: 10.1590/s2175-97902023e21115
Issue No: Vol. 59 (2023)
- Effect of Lyophilization on Stability of PEG-Protein Conjugate
Authors: Chintan Patel, Gayatri Patel
Pages: e201120 - e201120
Abstract: The purpose of the present study was to develop stable lyophilized formulation of peginterferon alfa-2b which is acquiescent to the short lyophilization process. The present study evaluates the effect of buffering components and cryoprotectant(s) on depegylation of the peginterferon alfa-2b in combination with lyophilization process. Finally, a short lyophilization process was identified which can produce a stable pharmaceutical form of peginterferon alfa-2b without any depegylation during long-term storage. Formulations were analyzed mainly for depegylation by HP-size exclusion chromatography and in-vitro antiviral activity. Residual moisture content in the lyophilized product was also used as a key indicating parameter to check its role with respect to depegylation upon storage under various temperature conditions. It was observed that the peginterferon alfa-2b when formulated in presence of cryoprotectant like sucrose requires longer lyophilization process of about 5 days, irrespective of the buffering components used, to reduce the level of residual moisture content and thereby to produce the stable formulation without depegylation. A stable formulation in presence of high concentration of lactose as a cryoprotectant was developed which can withstand stresses exerted to protein-polymer conjugate during lyophilization phases without any significant depegylation. A short lyophilization process of about 48 hours can be utilized for peginterferon alfa-2b when formulated in presence of lactose as a cryoprotectant through which a stable lyophilized formulation can be produced as against longer process required when sucrose is used a cryoprotectant, which is essential from commercial point of view as lyophilization is a costly process.
PubDate: 2023-04-28
DOI: 10.1590/s2175-97902023e201120
Issue No: Vol. 59 (2023)
- Effect of quercetin and role of nitric oxide pathway in
chloroquine-induced scratching
Authors: Osman Kukula, Caner Günaydın
Pages: e201085 - e201085
Abstract: Nitric oxide (NO) is an abundant mediator which is demonstrated to be involved in pruritus. Assuming that the increased NO also mediates chloroquine-induced pruritus, which is a frequent complication seen in the chronic chloroquine treatment, the current study aimed to investigate the effect of quercetin and the role of NO in chloroquine-induced pruritus in C57BL/6 mice. Model was created with subcutaneous chloroquine (400µg/site) injection to the nape of the mice. Effect of quercetin and role of NO were investigated with administration of quercetin, and co-administration with L-NAME, 7-NI and L-arginine before chloroquine injection. Locomotor activity was assessed by activity cage and number of the scratching bouts after chloroquine injection was recorded for 30 minutes. Our results show that quercetin significantly reduced scratching bouts at the doses of 10, 20, 40 and 80 mg/kg. Locomotor activity was decreased at the 40 and 80 mg/kg doses of quercetin. Additionally, decrease of the number of scratching bouts by quercetin prevented by L-arginine treatment, while L-NAME and 7-NI enhanced the anti-pruritic effect of sub-effective doses of quercetin. Therefore, our study demonstrated that acute injection of quercetin significantly diminished chloroquine-induced scratching behavior, and this effect is partly mediated by inhibition of neuronal nitric oxide synthase enzyme.
PubDate: 2023-04-28
DOI: 10.1590/s2175-97902023e201085
Issue No: Vol. 59 (2023)
- Use of bacaba peel for the development of hydroelectrolytic beverages and
their consumer acceptance
Authors: Luana Baldissera, Bryan Wender Debiasi, Juliana da Silva Agostini, Elton Brito Ribeiro, Marina Mariko Sugui, Carla Regina Andrighetti, Dênia Mendes Sousa Valladão
Pages: e21762 - e21762
Abstract: The hydroelectrolytic beverages segment has been expading its market and introducing new flavors in order to meet the demand for new products. However, experimental studies find concerns about the chemical compositions of these drinks. The aim of this study was to develop a drink without synthetic coloring or flavoring, with functional attributes based on the bacaba (Oenocarpus bacaba Mart.) peel extract. Two hydroelectrolytic drinks were developed, one hypotonic and the other isotonic, containing 0.5 and 1.0% of bacaba peel extract. Physicochemical characterization, determination of total phenolic compounds, anthocyanins, and antioxidant capacity were perfomed, in addition to color evaluation, as well as sensory analysis by means of preference tests. The developed formulations showed potential antioxidant activity and natural red coloring due to the phenolic compounds and anthocyanins present in the beverages. The sensory evaluation indicated positive acceptance by the tasters regarding the addition of the bacaba peel extract to the beverage formulations. The developed formulations demonstrated that the use of the bacaba peel is a viable option for the production of sports drinks, acting as a natural dye and offering health benefits due to its bioactive compounds.
PubDate: 2023-04-28
DOI: 10.1590/s2175-97902023e21762
Issue No: Vol. 59 (2023)
- Liquid chromatography-mass spectrometry for simultaneous determination of
spironolactone and canrenone in plasma samples
Authors: Ricardo Ferreira-Nunes, Edson A. T. Almeida, Marcílio S.S Cunha-Filho, Taís Gratieri, Guilherme Martins Gelfuso
Pages: e21626 - e21626
Abstract: In our study, we aimed to validate a method based on liquid chromatography-mass spectrometry (LC-MS) to quantify spironolactone (SPI) and its active metabolite canrenone (CAN) simultaneously in plasma samples to support in vivo experiments. Compounds were separated by using a C18 column with the isocratic elution of a mobile phase composed of 0.1% (v/v) formic acid in methanol-water (60:40 v/v) at a flow rate of 0.4 mL min−1. SPI and CAN were detected in na electrospray interface operating in a positive ionization mode and quantified using the selective ion mode monitoring of mass-charge ratios (m/z) of 439.0 for SPI and 363.1 for CAN. After calculating the matrix effect using theoretical equations, we observed the strong interference of plasma in the equipment-generated signal, which required creating analytical curves using the matrix as a solvent. The method was nevertheless linear (r 2 > 0.999) in a concentration range of 0.4-5.0 μg mL−1, as well as precise, with a coefficient of variation less than 5%. SPI’s and CAN’s recovery rates from the plasma ranged from 87.4% to 112.1%, while their limits of detection (i.e., 0.07 μg mL−1 and 0.03 μg mL−1, respectively) and quantification (i.e., 0.20 μg mL−1 and 0.08 μg mL−1, respectively) in the presence of plasma contaminants were low. Therefore, the bioanalytical method seems to be feasible for quantifying SPI and CAN in plasma.
PubDate: 2023-04-28
DOI: 10.1590/s2175-97902023e21626
Issue No: Vol. 59 (2023)
- Study on the effect of processing methods on the total polyphenol,
2,3,5,4’-tetrahydroxystilben-2-O-β-D-glucoside, and physcion contents
in Fallopia multiflora Thunb. Haraldson root
Authors: Thanh Thi Hong Nguyen, Tham Thi Hong Nguyen, Thang Dinh Tran, Chinh Thuy Nguyen, Luyen Dinh Nguyen, Luyen Thi Thuy Bui
Pages: e21570 - e21570
Abstract: This study investigated the changes in the ingredients in Fallopia multiflora Thunb. Haraldson (FMT) root after processing it with different methods such as soaking, stewing, and steaming or combined methods. The total polyphenol, 2,3,5,4′-tetrahydroxystilben-2-O-β-D-glucoside (THSG), and physcion contents in FMT products after processing were determined using high-performance liquid chromatography (HPLC) and ultraviolet-visible (UV-VIS) methods. The results demonstrated that the processing method and time significantly affected the contents of polyphenol, THSG, and physcion. The physcion and total polyphenol content increased or decreased during processing depending upon the processing time, while the THSG content gradually decreased with an increase in the processing time. The content of physcion (a substance that can cause liver toxicity) was analysed, and the suitable conditions for processing of the FMT products were determined as initial soaking in rice swill for 24 h and subsequent stewing with black beans and water for 12 h.
PubDate: 2023-04-28
DOI: 10.1590/s2175-97902023e21570
Issue No: Vol. 59 (2023)
- Effect of combined sedation using multiple drugs on inflammatory cytokines
in patients with acute respiratory distress syndrome
Authors: Xiangbi Nie, Liqiong Lou, Hui Xu, Wei Xiong, Zenggeng Wang
Pages: e21461 - e21461
Abstract: The innate immune response plays an important role in the pathophysiology of acute respiratory distress syndrome (ARDS); however, no drug has been proven to be beneficial in the management of ARDS. Therefore, the aim of this study was to investigate the effects of using combined sedatives on systemic inflammatory responses in patients with ARDS. A total of 90 patients with ARDS and an intubation time of > 120 h were randomly divided into the propofol group (group P), midazolam group (group M), and combined sedation group (group U). Patients in groups P and M were sedated with propofol and midazolam, respectively, whereas patients in group U were sedated with a combination of propofol, midazolam, and dexmedetomidine. The dosage of sedatives and vasoactive drugs, duration of mechanical ventilation, and incidence of sedative adverse reactions were documented. The dosage of sedatives and vasoactive drugs, as well as the incidence of sedative adverse reactions in group U, was significantly lower than those in groups P and M. Similarly, the duration of mechanical ventilation in group U was significantly shorter than that in groups P and M. Hence, inducing sedation through a combination of multiple drugs can significantly reduce their adverse effects, improve their sedative effect, inhibit systemic inflammatory responses, and improve oxygenation in patients with ARDS.
PubDate: 2023-04-28
DOI: 10.1590/s2175-97902023e21461
Issue No: Vol. 59 (2023)
- University Pharmacy
Authors: Eduardo Ricci-Junior, Denise de Abreu Garófalo, Maria Amélia Geraldes Bordalo Mont´Alverne, Márcia Maria Barros dos Passos, Melanie Tavares, Zaida Maria Faria de Freitas, Elisabete Pereira dos Santos, Mariana Sato de Souza Bustamante Monteiro
Pages: e21425 - e21425
Abstract: The University Pharmacy Program (FU), from the Federal University of Rio de Janeiro (UFRJ), was created based on the need to offer a curricular internship to students of the Undergraduate Course at the Faculty of Pharmacy. Currently, it is responsible for the care of about 200 patients/day, offering vacancies for curricular internships for students in the Pharmacy course, it has become a reference in the manipulation of many drugs neglected by the pharmaceutical industry and provides access to medicines for low-income users playing an important social function. Research is one of the pillars of FU-UFRJ and several master and doctoral students use the FU research laboratory in the development of dissertations and theses. As of 2002, the Pharmaceutical Care extension projects started to guarantee a rational and safe pharmacotherapy for the medicine users. From its beginning in 1982 until the current quarantine due to the COVID-19 pandemic, FU-UFRJ has been adapting to the new reality and continued to provide patient care services, maintaining its teaching, research, and extension activities. The FU plays a relevant social role in guaranteeing the low-income population access to special and neglected medicines, and to pharmaceutical and education services in health promotion.
PubDate: 2023-04-28
DOI: 10.1590/s2175-97902023e21425
Issue No: Vol. 59 (2023)
- Antimalarials and macrolides
Authors: Paulo Michel Pinheiro Ferreira, Rayran Walter Ramos de Sousa, Dalton Dittz, João Marcelo de Castro e Sousa, Francisco Leonardo Torres-Leal, Daniel Pereira Bezerra
Pages: e21067 - e21067
Abstract: We critically analyzed clinical trials performed with chloroquine (CQ) and hydroxychloroquine (HCQ) with or without macrolides during the first wave of COVID-19 and discussed the design and limitations of peer-reviewed studies from January to July 2020. Seventeen studies were eligible for the discussion. CQ and HCQ did not demonstrate clinical advantages that justified their inclusion in therapeutic regimens of free prescription for treatment or prophylactic purposes, as suggested by health authorities, including in Brazil, during the first wave. Around August 2020, robust data had already indicated that pharmacological effects of CQ, HCQ and macrolides as anti-SARS-CoV-2 molecules were limited to in vitro conditions and largely based on retrospective trials with low quality and weak internal validity, which made evidence superficial for decision-making. Up to that point, most randomized and nonrandomized clinical trials did not reveal beneficial effects of CQ or HCQ with or without macrolides to reduce lethality, rate of intubation, days of hospitalization, respiratory support/mechanical ventilation requirements, duration, type and number of symptoms, and death and were unsuccessful in increasing virus elimination and/or days alive in hospitalized or ambulatory patients with COVID-19. In addition, many studies have demonstrated that side effects are more common in CQ-or HCQ-treated patients.
PubDate: 2023-04-28
DOI: 10.1590/s2175-97902023e21067
Issue No: Vol. 59 (2023)
- Counterfeit medicines
Authors: Marcela Bittar Araujo Lima, Mauricio Yonamine
Pages: e20402 - e20402
Abstract: Counterfeiting of medicines, also known as “falsification” or “adulteration”, is the process in which the identity, origin, or history of genuine medicines are intentionally modified. Currently, counterfeit medicines are a global crisis that affects and is mostly caused by developing countries in Asia, Africa and Latin America. These countries lack strict law enforcement against this practice and have low-income populations with medicinal needs. Lately, the crisis has escalated, impacting developed countries as well, e.g., the US and the EU, mainly via the Internet. Despite this extension, some current laws aim to control and minimize the crisis’ magnitude. Falsification of medicines maintains an illegitimate supply chain that is connected to the legitimate one, both of which are extremely complex, making such falsification difficult to control. Furthermore, political and economic causes are related to the crisis’ hasty growth, causing serious consequences for individuals and public health, as well as for the economy of different countries. Recently, organizations, technologies and initiatives have been created to overcome the situation. Nevertheless, the development of more effective measures that could aggregate all the existing strategies into a large functioning network could help prevent the acquisition of counterfeit medicines and create awareness among the general population.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902023e20402
Issue No: Vol. 59 (2023)
- Resveratrol inhibits nicotine-induced conditioned place preference in mice
Authors: Oruç Yunusoğlu
Pages: e20883 - e20883
Abstract: Nicotine addiction leads to in a huge burden on public health and the economy worldwide. Resveratrol (3,5,4’-tetrahydroxystilbene) is the most well-known polyphenolic stilbenoid. Resveratrol was shown to exhibit positive effects on numerous mechanisms that are important for drug and substance addiction. Thus, this study aimed to examine the effect of resveratrol on nicotine addiction. Intraperitoneal (i.p.) treatment with nicotine (0.5 mg/kg) significantly enhanced time spent in the nicotine-paired compartment. Resveratrol (50 and 75 mg/kg, i.p.) and varenicline (2 mg/kg, i.p.) co-administered with nicotine during the 3-day conditioning period effectively diminished the acquisition of nicotine-induced conditioned place preference (CPP). On the other hand, the administration of resveratrol (50 and 75 mg/kg, i.p.) and varenicline (2 mg/kg, i.p.) decreased the low dose (0.1 mg/kg, i.p.) nicotine-induced reinstatement. The results suggest that resveratrol and varenicline inhibit the acquisition and reinstatement of nicotine’s reward properties. Resveratrol displayed similar results in the CPP phases as obtained with the reference drug varenicline. In conclusion, resveratrol could be beneficial as an adjuvant pharmacotherapy for nicotine addiction; however, more investigation is needed to completely explain this property.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902023e20883
Issue No: Vol. 59 (2023)
- The activity of propolis against pathogenic fungi isolated from human
infections
Authors: Katarzyna Wolska, Katarzyna Antosik
Pages: e19978 - e19978
Abstract: Propolis is a resinous hive product collected by bees from the buds or other parts of plants. It is known for having various biological properties, including antifungal activity. Among the substances present in propolis, flavonoids and phenolic acids and their esters are responsible for its antifungal properties. This means that propolis is ideal for use as an antifungal agent in alternative medicine to treat a number of both topical and systemic infections caused by Candida species and other yeast-like fungi, dermatophyte and nondermatophyte moulds, without the serious side effects typical of synthetic treatment. It is also active against strains of fungi that are resistant to polyenes and azoles, the classes of drugs most commonly used to treat fungal infections. In this article, we review current knowledge about the activity of propolis from different parts of the world and its components in vitro and in vivo against pathogenic fungi isolated from human infections. The article also indicates the possible mechanism of antifungal activity of propolis and its components.
PubDate: 2023-04-14
Issue No: Vol. 59 (2023)
- Mannich bases derivatives of 2-Phenyl-5-Benzimidazole sulfonic acid;
Synthesis, Characterization, Computational studies and Biological
evaluation
Authors: Muhammad Qasim Khan , Naseem Ullah, Samra Farooq
Pages: e19544 - e19544
Abstract: A new series of N-Mannich bases of 2-Phenyl-5-benzimidazole sulfonic acid have been synthesized through amino methylation reaction with secondary amines. The two moieties were held together through a methylene bridge, which comes from formaldehyde (Formalin Solution 37%) used in the reaction. Chemical structures of the newly synthesized compounds have been confirmed using FT-IR, 1HNMR and 13CNMR. Different in vitro assays including Anti-oxidant, Enzyme inhibition, Anti-microbial and Cytotoxicity assay were performed to evaluate the biological potential with reference to the standard drug. Among the synthesized library, compound 3a shows maximum alpha-glucosidase inhibition with an IC50 value of 66.66 μg/ml, compound 3d was found most toxic with LC50 value of 10.17 μg/ml. ADME evaluation studies were performed with the help of Molinspiration online software. Docking calculations were also performed. Given the importance of the nucleus involved, the synthesized compound might find extensive medicinal applications as reported in the literature.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902023e19544
Issue No: Vol. 59 (2023)
- Mechanical, optical, and physicochemical properties of HPMC-based
doxazosin mesylate orodispersible films
Authors: Pamela Coradi da Silva, Larissa Aroca Colucci, Larissa Lea da Silva, Celso Molina, Marcelo Dutra Duque, Leticia Norma Carpentieri Rodrigues
Pages: e21114 - e21114
Abstract: In this study, orodispersible films formed from hydroxypropyl methylcellulose (HPMC) E6 (2, 2.5, and 3%) and plasticizers ((glycerin (Gly), propylene glycol (PP), or polyethylene glycol (PEG)), containing doxazosin mesylate, were prepared by the solvent casting method and characterized. Design of experiments (DoE) was used as a statistical tool to facilitate the interpretation of the experimental data and allow the identification of optimal levels of factors for maximum formulation performance. Differential scanning calorimetry (DSC) curves and X-ray powder diffraction (XRPD) diffractograms showed doxazosin mesylate amorphization, probably due to complexation with the polymer (HPMC E6), and the glass transition temperature of the polymer was reduced by adding a plasticizer. Fourier transformed infrared (FTIR) spectroscopy results showed that the chemical structure of doxazosin mesylate was preserved when introduced into the polymer matrix, and the plasticizers, glycerin and PEG, affected the polymer matrix with high intensity. The addition of plasticizers increased the elongation at break and adhesiveness (Gly > PEG > PP), confirming the greater plasticizer effect of Gly observed in DSC and FTIR studies. Greater transparency was observed for the orodispersible films prepared using PP. The addition of citric acid as a pH modifier was fundamental for the release of doxazosin mesylate, and the desirability formulation had a release profile similar to that of the reference product.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902023e21114
Issue No: Vol. 59 (2023)
- Development of a validated stability-indicating HPLC- DAD method for
dasabuvir and the characterization of its degradation products using
LC-QToF-MS/MS
Authors: Allan Michael Junkert, Breno Maurício Marson, Mariana Millan Fachi, Raquel de Oliveira Vilhena, Beatriz Böger, Roberto Pontarolo
Pages: e21480 - e21480
Abstract: A stability-indicating HPLC-DAD method was developed and validated for the simultaneous determination of dasabuvir and its degradation products in the pharmaceutical formulation. The proposed method utilized a Symmetry® C18 (4.6 x 75 mm, 3.5 µm) column, and the mobile phase consisted of an isocratic elution of formic acid (0.1%) and acetonitrile (55:45, v/v), at a flow of 1 mL min-1; analytes were detected at 244 nm. Dasabuvir was submitted to different stress degradation conditions, such as acidic, alkaline, neutral, thermal, oxidative and photolytic, and the structural elucidation of degradation products was performed using LC-QToF-MS/MS. The HPLC-DAD stability-indicating method was validated for selectivity, linearity, limit of detection and quantification, accuracy, precision and robustness, according to ICH guidelines. Dasabuvir produced two degradation products (DP1 and DP2) from the alkaline stress conditions, which were characterized in negative ion mode. Dasabuvir was linear in the range 9.78 to 136.92 µg mL-1, and DP and DP were linear in the range 2.9 to 20.2 µg mL-1 and 1.3 to 14.9 µg mL-1, respectively. The 1 2 recovery ranged between 99.16 and 100.86%, while precision ranged from 1.02 to 2.89%. As the method can effectively separate the dasabuvir from its degradation products and quantitate them, it may be employed as a stability-indicating method for the pharmaceutical formulation.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902023e21480
Issue No: Vol. 59 (2023)
- Long-term resveratrol administration improves diabetes-induced pancreatic
oxidative stress, inflammatory status, and β cell function in male rats
Authors: Samin Nahavandi, Masoumeh Rahimi, Mohammad Reza Alipour, Farhad Ghadiri Soufi
Pages: e21468 - e21468
Abstract: Diabetes is a metabolic disorder caused by insulin resistance or a defect in the pancreatic beta cells in insulin secretion. The aim of this study was to evaluate the possible effectiveness of long-term administration of resveratrol on inflammatory and oxidative stress markers in the pancreatic tissue of diabetic rats. Male Wistar rats (n = 24) were randomly divided into four groups of six animals, namely a healthy group, a healthy group receiving resveratrol, a diabetic control group, and a diabetic group receiving resveratrol. Diabetes was induced by single dose injection of streptozotocin (50 mg/kg; ip), 15 min after injection of nicotinamide (110 mg/kg; ip). Resveratrol was also administered by gavage (5 mg/kg/day) for 4 months. Administration of resveratrol alleviated hyperglycemia, weight loss and pancreatic β cell function measured by HOMA-β. Resveratrol improved oxidative stress (nitrate/nitrite, 8-isoprostane and glutathione) and proinflammatory markers (tumor necrosis factor α, cyclooxygenase 2, interleukin 6 and nuclear factor kappa B) in the pancreatic tissue of diabetic rats. Resveratrol administration had no significant effect on the activity of superoxide dismutase and catalase enzyme. These observations indicate that resveratrol administration may be effective as a beneficial factor in improving pancreatic function and reducing the complications of diabetes.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902023e21468
Issue No: Vol. 59 (2023)
- The Protective Effects of Geraniol Against Damage of Short Term Renal
Ischemia-Reperfusion in Rats
Authors: Seren Danış, Senanur Can, Fatma Yıldız, Işıl Tan Yılmaz, Mediha Canbek, Ayşe Özmen Yaylacı
Pages: e21248 - e21248
Abstract: Ischemia/reperfusion (I/R) injury is one of the main causes of acute kidney injury. The pathological mechanisms underlying renal I/R injury are complex and remain uncertain. The protective effects of antioxidant properties of geraniol against renal ischemia reperfusion (I/R) damage were investigated in our study. 28 Wistar albino male rats were randomly selected and 4 groups of n = 7 were created. A right kidney nephrectomy surgery was conducted to all groups under anesthesia. 2 ml SF was given to Groups I and II, 50 mg/kg and 100 mg/ kg geraniol were administered intraperitoneally an hour before ischemia to Groups III and IV, respectively. Except for Group I, 45 minutes of ischemia and 4 hours of reperfusion were applied to the groups. At the end of the experiment, parameters related to oxidative stress and inflammation were determined by comparing kidney function, antioxidant enzyme activities and histological changes. Following comparison of BUN and CRE values with CAT and SOD values in tissue samples of Group I and Group II, an increase in Group II was observed and as a result I/R damage formation occurred. Values of geraniol-treated Group III and Group IV approximated to that of Group I, and that the 50 mg/kg geraniol dose proved more effective than 100 mg/kg geraniol.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902023e21248
Issue No: Vol. 59 (2023)
- Outpatient pharmaceutical office
Authors: Belmiro Morgado Junior, César Augusto Abreu-Pereira, Maria Amelia Zanon Ponce, Rosana De Gasperi Pagliuso, Adriana Melo Jorge Santos, Adriane Lopes Medeiros Simone
Pages: e21244 C - e21244 C
Abstract: We evaluated the implementation of the outpatient pharmaceutical office in a teaching hospital regarding the access to medicines available in the Unified Health System - SUS. This is a descriptive-analytical study, based on secondary data analysis of 735 appointments performed by the pharmacist from 2015 to 2017. Of the drugs prescribed to patients attended at the outpatient pharmacist office, 86.39% were listed in the National List of Essential Medicines - RENAME, of which 95.43% belonged to the Specialized Component of Pharmaceutical Assistance. Evaluating the patient’s diagnosis against the inclusion criteria of the Clinical Protocols and Therapeutic Guidelines (PCDT), that the most frequent pharmaceutical interventions were: adequacy of the medication request documents (56.4%) and examination requests for pharmacotherapeutic follow up (28.5%). When the prescribed drugs were not included in RENAME/PCDT, the intervention was accepted in 90.3% of the proposals for exchange with available drug in SUS. Still, it was possible to refer the patient to primary care for renewal of continuity of treatment in 95.1% of cases. In conclusion, the role of the clinical pharmacist contributes to the resolution of untreated health problems by promoting access to medicines within the scope of SUS and their rational use in accordance with the PCDT.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902023e21244
Issue No: Vol. 59 (2023)
- The effects of metformın, acetylsalıcylıc acıd and ıbuprofen on
telomerase enzyme actıvıty
Authors: Aykut Topal, Irem Alkan, Didem Korkmaz, Hulya Yildiz, Muazzez Tikirdik, Ayse Gul Mutlu
Pages: e21233 - e21233
Abstract: Telomerase enzyme is necessary for the elongation of telomeres while telomerase being critical for aging and cancer. Metformin, ibuprofen, and acetylsalicylic acid used in this research are drugs that millions of people already use and that many are likely to use in future. In this study, the effects of these drugs on telomerase activity of Mus musculus swiss albino mice in liver tissue were investigated and the telomerase activity was measured with a PCR-ELISA based kit. In the study a possible connection between telomerase enzyme activity and activities of antioxidant enzymes was also investigated by determining the activity of superoxide dismutase (SOD) and catalase enzymes. The data obtained show that metformin slightly decreased telomerase enzyme activity in low dose application; however, this change was not statistically significant. In ibuprofen application, there was a significant inhibitory effect when high doses were used; whereas, there was a slight inhibitory effect at low doses. In acetylsalicylic acid application, a slight activator effect was detected; it was not statistically significant, though. Metformin was observed to increase catalase and SOD activities in general while low and high doses of acetyl salicylic acid showed different effects. In addition, ibuprofen caused a statistically significant increase in liver SOD values. It is important to note that this study demonstrated a significant inhibitory effect of ibuprofen on telomerase enzyme activity in animal models.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902022310233
Issue No: Vol. 59 (2023)
- Network pharmacology strategy to investigate the pharmacological effects
of Suanzaoren Decoction on insomnia
Authors: Xiaojian Weng, Jimin Jiang, Hailong Li , Yi Tan
Pages: e21182 - e21182
Abstract: Suanzaoren Decoction (SZRD) is an ancient prescription used in the treatment of insomnia. This study aimed to investigate the components and targets of SZRD in treating insomnia. First, the compounds of five herbs in SZRD were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the putative targets for treating insomnia were obtained from DrugBank to construct the herb-compound-target- disease network. A protein-protein interaction (PPI) network was constructed in the STRING database, and then Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the mechanism of action of intersection target. Finally, 30 mice were divided into five groups: control, model, and quercetin groups (100, 50, 25 mg/kg). The sleep latency and duration of pentobarbital-induced sleeping were measured. The production of interleukin-6 (IL-6) and γ-aminobutyric acid (γ-GABA) was detected by using an enzyme-linked immunosorbent assay kit (ELISA), and Gamma-aminobutyric acid type a receptor subunit alpha1 (GABRA1) was tested by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). A total of 152 active ingredients, including 80 putative targets of SZRD, were obtained. The main active compounds included quercetin and kaempferol, and the key targets involved IL-6 and nitric oxide synthase 3 (NOS3). The results of pathway enrichment analysis indicated that the putative targets of SZRD mainly participated in Neuroactive ligand-receptor interaction. The experiment of P-chlorophenylalanine (PCPA)-induced insomnia model showed that quercetin obviously shortened the sleep latency and prolonged the sleep duration of the insomnia model. The production of IL-6, γ-GABA, and GABRA1 mRNA was significantly increased in mice treated with quercetin. This study predicted the active ingredients and potential targets of SZRD on insomnia on the basis of a systematic network pharmacology approach and illustrated that SZRD might exert hypnotic effects via regulating IL-6, γ-GABA, and GABRA1.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902023e21182
Issue No: Vol. 59 (2023)
- Chemical characterization, cytotoxicity, antimicrobial and antioxidant
potential of Justicia pectoralis Jacq and Croton jacobinensis Baill
extracts
Authors: Leilanne Márcia Nogueira de Oliveira, Maria do Socorro Rocha Bastos, Ana Cristina Silva de Lima, Evânia Altina Teixera de Figueiredo, Flayanna Gouveia Braga Dias, Larissa Morais Ribeiro da Silva, Selene Dahia Benevides, Paulo Riceli Vasconcelos Ribeiro, Luiz Bruno de Sousa Sabino *
Pages: e21224 - e21224
Abstract: In this research, aqueous and ethanolic extracts from Justicia pectoralis Jacq and Croton Jacobinensis Baill were characterized. The UPLC-QTOF-MSE analysis was performed on the extracts identified, predominantly, flavonoids, tannins and acids. The extracts did not indicate toxicity in human epithelial cells. C. jacobinensis presented a concentration of phenolics 60.5% higher than J. pectoralis in all scenarios evaluated and, for both samples, the hydroalcoholic extract at 70% exhibited the best efficiency in the extraction (14501.3 and 32521.5 mg GAE 100 g-1 for J. pectoralis and C. jacobinensis, respectively). The antioxidant activity presented a positive correlation with the concentration of phenolics, being 1.186,1 and 1.507,9 μM of Trolox for J. pectoralis and C. jacobinensis at 70% of ethanol; however, it was not verified statistical difference between the ethanolic solutions (p < 0.05). The antimicrobial activity of J. pectoralis extracts was highlighted once was the most effective against gram-positive bacteria. The results suggest that both J. pectoralis and C. jacobinensis extracts present the potential to be applied as natural additives due to their antioxidant and antimicrobial activity and safety. Thus, it is suggesting the development of studies that could investigate the interaction of these plant extracts with food matrices is required.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902023e21224
Issue No: Vol. 59 (2023)
- PVP solid dispersions containing Poloxamer 407 or TPGS for the improvement
of ursolic acid release
Authors: Andressa Maria Pironi, Josimar de Oliveira Eloy, Camila Fernanda Rodero, Selma Gutierrez Antonio, Jovan Duran Alonso, Marlus Chorilli
Pages: e21217 - e21217
Abstract: Solid dispersions (SDs) of ursolic acid (UA) were developed using polyvinylpyrrolidone K30 (PVP K30) in combination with non-ionic surfactants, such as D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) or poloxamer 407 (P407) with the aim of enhancing solubility and in vitro release of the UA. SDs were investigated using a 24 full factorial design, subsequently the selected formulations were characterized for water solubility, X-ray diffractometry (XRD), differential scanning calorimetry (DSC), particle diameter, scanning electron microscopy, drug content, physical-chemical stability and in vitro release profile. SDs showed higher UA water-solubility than physical mixtures (PMs), which was attributed by transition of the drug from crystalline to amorphous or molecular state in the SDs, as indicated by XRD and DSC analyses. SD1 (with P407) and SD2 (with TPGS) were chosen for further investigation because they had higher drug load. SD1 proved to be more stable than SD2, revealing that P407 contributed to ensure the stability of the UA. Furthermore, SD1 and SD2 increased UA release by diffusion and swelling-controlled transport, following the Weibull model. Thus, solid dispersions obtained with PVP k-30 and P407 proved to be advantageous to enhance aqueous solubility and stability of UA.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902023e21217
Issue No: Vol. 59 (2023)
- Blood glucose related adverse drug reaction of antitumor monoclonal
antibodies
Authors: Jincheng Yang, Lianzhen Chen
Pages: e18893 - e18893
Abstract: On the increasing prevalence of using mAbs (monoclonal antibodies) in cancer therapy and the severe risk of hyperglycemia, we aimed to analyze the main clinical ADRs of mAbs, with a focus on adverse hyperglycemic events associated with currently clinically used mAbs. mAbs as well as target information were selected from Martinadale book and published articles. Drug approving information was collected from each government website, and ADR statistic data were collected from VigibaseR, comparing with Adverse Event Reporting System of US FDA. Top 10 mAbs were classified within listing in total ADR records, ADRs per year, hyperglycemic ADR records. Vigibase data were updated onto 15 Feb 2019. 20 mAbs were analyzed with 263217 ADR reports, wherein 16751 records on Metabolism and nutrition disorders and 1444 records on Glucose metabolism disorders. The geographic, age, gender distributions and annual ADR report numbers were listed respectively. Of the top 10, Rituximab, Bevacizumab and Nivolumab were on the top 3 in total ADR record and hyperglycemic record. Top 3 record results were similar in Vigibase and FDA database. It is of increasing importance for clinicians to be aware of early detection, patient management, or drug selection strategies when using mAbs, particularly within the high glycemic risk-reported mAbs, to improve the efficacy and tolerability of mAbs regiment and optimize patient outcomes.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902020000118893
Issue No: Vol. 59 (2023)
- Immunochromatography screening devices for cannabinoids in oral fluid
sample
Authors: Jonathaline Apollo Duarte, Roberta Petry Gorziza, Marina González, João Marcelo Astolfi Picanço, Renata Pereira Limberger
Pages: e20555 - e20555
Abstract: Cannabis sativa L. is one of the most consumed drugs in the world and recent studies have associated its use with an increase in the number of traffic accidents in different countries. In many countries, like Brazil, simple and reliable methodologies are still needed for the detection of drugs on site, mainly cannabinoids, considering its prevalence of use and oral fluid (OF) has been proved as an appropriate biological matrix for this purpose. Considering that, this work aims to review previous studies on immunochromatographic devices for on-site detection of cannabinoids in OF, discussing their sensitivity, specificity, cut-offs values and confirmatory methods. This data shows the importance of choosing a screening device and it reinforces the need for its implementation in Brazil. The research was conducted on 5 databases and all original articles, published in the last 10 years, were selected. A total of 32 articles were found, providing data for 17 screening devices of distinct brands. Only 2 screening devices showed satisfactory sensitivity and specificity in the evaluated studies (≥80% and ≥90% respectively). However, it should be considered that the screening devices still have some limitations, such as a higher cut-off than those recommended by international guidelines (cut-off > 2 ng/mL), therefore demonstrating the need for more studies in the area and the importance of confirmatory analysis usually fulfilled by LC-MS/MS, GC-MS/MS or GC-MS. Thus, the screening analyzes should not be evaluated by itself, but in association with confirmatory results and observational traits (behavioral changes), for a better understanding of the traffic scenario.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902023e20555
Issue No: Vol. 59 (2023)
- The activity of propolis against pathogenic fungi isolated from human
infections
Authors: Katarzyna Wolska, Katarzyna Antosik
Pages: e19978 - e19978
Abstract: Propolis is a resinous hive product collected by bees from the buds or other parts of plants. It is known for having various biological properties, including antifungal activity. Among the substances present in propolis, flavonoids and phenolic acids and their esters are responsible for its antifungal properties. This means that propolis is ideal for use as an antifungal agent in alternative medicine to treat a number of both topical and systemic infections caused by Candida species and other yeast-like fungi, dermatophyte and nondermatophyte moulds, without the serious side effects typical of synthetic treatment. It is also active against strains of fungi that are resistant to polyenes and azoles, the classes of drugs most commonly used to treat fungal infections. In this article, we review current knowledge about the activity of propolis from different parts of the world and its components in vitro and in vivo against pathogenic fungi isolated from human infections. The article also indicates the possible mechanism of antifungal activity of propolis and its components.
PubDate: 2023-04-14
DOI: 10.1590/s2175-97902023e19978
Issue No: Vol. 59 (2023)
- Association of reproductive risk factors and comorbidities among molecular
subtypes of Breast cancer in a Tertiary care Hospital
Authors: Veintramuthu Sankar, Parthasarathy Rama
Pages: e18816 - e18816
Abstract: The reasons for the recently observed increase in the incidence of breast cancer in the Indian population
are not clearly understood, but thought to be largely explained by westernization of lifestyles and
changes in reproductive behavior, which characterize exposure to hormones. Our aim is to review the
reproductive risk factors and comorbidities and evaluate the association between molecular subtypes
of breast cancer. A hospital-based analytical case-control study was conducted among the breast
cancer cases with controls in a multispecialty teaching hospital for a period of one year. Totally, 130
subjects were recruited and an interview was conducted using a structured questionnaire to obtain
demographic and risk factor data, including tissue marker status (ER, PR and HER-2) obtained from
case files. Data were analyzed with SPSS-20 version. Results: The highest age group reported in this
study was 51- 60 years which has a 3.8 times increased risk compared to other age and the age group of
31- 40 have a decrease risk of 0.33. In this study, the percentage of post menopause (68%) and mothers
not breastfeeding (10%) was higher in cases compared to controls and a noted increase in the risk of
breast cancer with odds ratio (OR) of 2.745 (p= <0.0001) and 9.08 (p=0.01) respectively. Duration of
breastfeeding showed significantly (p=<0.0001)) moderate positive correlation (r=0.549, 0.457, 0.418
and 0.636) for luminal A, luminal B, HER+, and triple negative respectively. This study found that all
the reproductive risk factors do not have correlation with a molecular subtype of breast cancer except
breastfeeding. Post menopause and breastfeeding were common factors associated with all people
and could be modifiable to prevent the occurrence of breast cancer through lifestyle changes.
PubDate: 2023-03-14
Issue No: Vol. 59 (2023)
- In Vitro Evaluation of Dalbergia sissoo and Acacia modesta gum as
Pharmaceutical Binders for Drug Delivery System
Authors: Hira Munir, Muhammad Shahid
Pages: : e18745 - : e18745
Abstract: The present study aimed to compare the crude, modified and hydrolyzed gums of Dalbergia sissoo and Acacia modesta as a biodegradable binder for drug delivery system using acetaminophen as a model drug. The physiochemical properties such as pH, fluorescence analysis and swelling index were determined. The gums were hydrolyzed and modified. Acetaminophen tablets were prepared using wet granulation technique and the gum solutions were used as a binder. Hydroxypropyl methylcellulose was used as a synthetic binder. Different properties of granules and tablets were evaluated. Results showed that both gums were acidic in nature, while D. sissoo and A. modesta showed light brown and creamy color in fluorescence analysis. The swelling ratio was the highest in water followed by 0.1N HCl and least in phosphate buffer. The prepared tablets showed faster and slower dissolution profiles in the same dissolution system. The crude gums have the highest dissolution rate, and this rate was decreased in the case of modified and hydrolyzed gums samples. The crude gums showing slower release can be useful in sustained-release tablets, while the modified gums having faster release rate are helpful in conventional tablet formulation. Taken together, the selected gums could be a good model for evaluation as a binder or hydrophilic polymer in tablet formulation.
PubDate: 2023-03-14
Issue No: Vol. 59 (2023)
- Analgesic, antipyretic, anti-inflammatory, and hepatoprotective activities
of Pulicaria crispa (Forssk.) Oliv. (Asteraceae)
Authors: Hasan S. Yusufoglu
Pages: e18851 - e18851
Abstract: Some plants of the genus Pulicaria have been used in traditional medicines for treating back pain and inflammation. They possess various bioactivities such as antipyretic, analgesic, and hepatoprotective. This study aimed to investigate the potential analgesic, antipyretic, anti- inflammatory, and hepatoprotective activities of Pulicaria crispa (P. crispa) extract (PCE). Analgesic activity was evaluated using the hot plate and acetic acid-induced writhing tests. Antipyretic and anti-inflammatory activities were evaluated using rectal temperature and carrageenan-induced hind paw edema methods, respectively. CCl4-intoxication was used for hepatoprotective activity. Also, liver histopathology was assessed. PCE, at 500 mg/kg, exhibited significant analgesic, antipyretic, and anti-inflammatory effects. The increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bilirubin of CCl4-exposed rats reflects their liver injury. PCE significantly decreased the elevated liver markers. The hepatoprotective effect of PCE was confirmed, as it successfully reversed the altered levels of total protein, malondialdehyde (MDA), and non-protein sulfhydryls (NP-SH) in the liver tissues of CCl4-exposed rats. Histopathological studies confirmed the hepatoprotective nature of PCE. Pretreatment of rats with PCE reduced the severity of CCl4-induced liver damage. These findings concluded that PCE possesses analgesic, antipyretic, anti-inflammatory, and hepatoprotective activities.
PubDate: 2023-03-14
DOI: 10.1590/s2175-97902022e18851
Issue No: Vol. 59 (2023)
- ynthetic berberine derivatives as potential new drugs
Authors: Mensura Sied Filli, Ahmed Abdalla Ibrahim, Md Aquib, Kofi Oti Boakye-Yiadom, Samuel Kesse, Muhammad Asim Farooq, Bo Wang, Faisal Raza
Pages: e18835 - e18835
Abstract: The modern process of new drug discovery and development is an exciting, yet a challenging, endeavor. Although it can result in significant financial income and meet the medical needs of patients, it ultimately may result in failure. To achieve a fast and successful new product discovery and development process, natural products which are evolutionarily optimized as drug-like molecules have gained great attention as better potential sources of new chemical entities. Historically, plant species containing berberine are used in various traditional phytotherapy. However, despite the various therapeutic effects it exerts, berberine is not yet developed into a drug product. Addressing the barriers that hinder its successful development and the efforts made to overcome them is thus crucial. The toxicological and pharmacokinetic properties of berberine are the main barriers towards its development into a marketed drug product. It has low aqueous solubility, poor absorption, fast metabolism, and wide tissue distribution which lead to low bioavailability limiting its clinical application. Synthetic berberine derivatives with improved properties are suggested as better alternatives for further development and future therapeutic application. Hence, this paper summarizes the preclinical research studies conducted in the last decade to reveal the therapeutic potential of synthetic berberine derivatives for the treatment of various diseases and hence achieve successful berberine-based drug development in the future. To exploit the value of natural products as a source of leads for the development of effective drugs, collaboration among the different discovery and development scientists is essential.
PubDate: 2023-03-14
DOI: 10.1590/s2175-97902020000318835
Issue No: Vol. 59 (2023)
- Development and validation of a HILIC-HPLC-ELSD method for simultaneous
determination of glucosamine hydrochloride and chondroitin sulfate in
dietary supplements
Authors: Mochammad Yuwono
Pages: e20686 - e20686
Abstract: The objective of the present study is to develop and validate a simple, selective and accurate hydrophilic interaction liquid chromatography - a high performance liquid chromatography incorporating an evaporative light scattering detector (HILIC-HPLC-ELSD) method for simultaneously determining glucosamine hydrochloride and chondroitin sulfate in dietary supplements. The chromatographic separation was carried out on a ZIC-HILIC column (150 mm x 4.6 mm x 5µm) in isocratic system mode with a mobile phase of acetonitrile, 30 mM ammonium formate and water (77:20:3, v/v/v) at pH 4.5, a column temperature of 35°C, a flow rate of 1 mL.min-1, and an injection volume of 5 µL. An evaporative light scattering (ELS) detector was used. Effective separation was achieved by means of analyte resolution of more than 1.5 with an analysis run time of approximately 20 minutes. The linearity of glucosamine hydrochloride and chondroitin sulfate ranged from 0.4 to 2.5 mg.mL-1. The limits of the detection and quantification of glucosamine hydrochloride were 20 and 80 mg.mL-1 respectively, while for chondroitin sulfate they were 80 and 400 mg.mL-1. All validation parameters satisfied the acceptance criteria in accordance with International Conference on Harmonisation (ICH) guidelines. The method was successfully applied to the assay of commercial dietary supplement samples.
PubDate: 2023-02-17
Issue No: Vol. 59 (2023)
- Focal adhesion kinase inhibition decreases cell viability and induces
apoptosis of JAK2 V617F positive cells
Authors: Ana Carolina Menezes Mendonça Valente, Gustavo Henrique Lima de Farias, Ana Cristina Ribeiro Bernardo, Caio Cesar de Souza Alves, Michelle Bueno de Moura Pereira, Raquel Tognon-Ribeiro
Pages: 7 - 7
Abstract: Focal Adhesion Kinase (FAK) protein participates in proliferation, migration, cell survival, and apoptosis process. It has been described as overexpressed in several neoplasms being a promising target for therapy. BCR-ABL negative chronic Myeloproliferative Neoplasms (MPN) are clonal disorders characterized by the excess of proliferation and apoptosis resistance. The identification of the acquired JAK2 V617F mutation in MPN patients allowed a better understanding of pathogenesis. However, there is still no pharmacological treatment that leads all patients to molecular remission, justifying new studies. The present study aimed to evaluate FAK involvement in the viability and apoptosis of HEL and SET-2 cells, both JAK2 V617F positive cell lines. The FAK inhibitor PF 562,271 was used. Cell viability was determined using MTT assay and apoptosis verified by cleaved PARP, cleaved Caspase 3 and Annexin-V/PI staining detection. FAK inhibition significantly reduced HEL and SET-2 cells viability and induced apoptosis. Considering the role of JAK/STAT pathway in MPN, further investigation of FAK participation in the MPN cells proliferation and apoptosis resistance, as well as possible crosstalk between JAK and FAK and downstream pathways may contribute to the knowledge of MPN pathophysiology, the discovery of new molecular targets, and JAK inhibitors resistance mechanisms.
PubDate: 2023-08-28
Issue No: Vol. 59 (2023)
- Effect of polycaprolactone nanocapsules loaded with essential oils on
biofilm formation by Staphylococcus aureus strains isolated from bovine
mastitis cases
Authors: Gabriela Suthovski, Alcione Santa Catarina, Diana Paula Perin, Diana Paula Perin, Rubiana Mara Mainardes, Karina Ramirez Starikoff, André Lazarin Gallina, Maiara Garcia Blagitz Azevedo, Fabíola Dalmolin, Luciana Velasques Cervo, Dalila Moter Benvegnú
Pages: 13 - 13
Abstract: Bovine infectious mastitis is largely resistant to antibacterial treatment, mainly due to mechanisms of bacterial resistance in the biofilms formed by Staphylococcus aureus. Melaleuca (MEO) and citronella essential oils (CEO) are promising agents for reducing or eliminating biofilms. Free melaleuca oil presented a medium Minimum Inhibitory Concentration (MIC) of 0.625% and a Minimum Bactericidal Concentration (MBC) of 1.250%, while free citronella oil showed medium MIC and MBC of 0.313%. Thus, free CEO and MEO demonstrate bacteriostatic and bactericidal potential. We generated polymeric nanocapsules containing MEO or CEO and evaluated their efficacy at reducing biofilms formed by S. aureus. Glass and polypropylene spheres were used as test surfaces. To compare the responses of free and encapsulated oils, strains were submitted to 10 different procedures, using free and nanoencapsulated essential oils (EOs) in vitro. We observed no biofilm reduction by MEO, free or nanoencapsulated. However, CEO nanocapsules reduced biofilm formation on glass (p=0.03) and showed a tendency to diminish biofilms on polypropylene (p=0.051). Despite nanoencapsulated CEO reducing biofilms in vitro, the formulation could be improved to modify the CEO component polarity and, including MEO, to obtain more interactions with surfaces and the biofilm matrix.
PubDate: 2023-08-28
Issue No: Vol. 59 (2023)
- Experimental acute anti-inflammatory activity of preparations with
complexed cannabidiol in carriers
Authors: Daniel Ribeiro Grijó, Edvalkia Magna Teobaldo da Rocha, Vitor de Cinque Almeida, Ciomar Aparecida Bersani Amado, José Eduardo Olivo, Oswaldo Curty da Motta Lima
Pages: 19 - 19
Abstract: Cannabidiol (CBD) is a bioactive compound with promising anti-inflammatory results but has low aqueous solubility. Complexation of drugs with this characteristic in carriers is an alternative to improve their efficiency. This study aimed to prepare and characterize CBD complexes in different carriers, and to evaluate the anti-inflammatory effect of such preparations using an experimental model of edema induction in rat paws. The results were compared to a reference drug, ibuprofen (IBU). The carriers evaluated were beta cyclodextrin (bCD) and activated charcoal (AC). Quantification of the drugs in the complexes was determined, and different qualitative analyses were also performed. Oral treatments in single doses with CBD showed inhibitory effects similar to that of IBU, potentiating its bioactivity without significant adverse effects. CBD*bCD doses at 4.375, 8.75, 17.5, and 35 mg/kg significantly reduced the intensity of edema compared to equivalent doses of pure bioactive. In contrast, CBD*AC did not generate benefits. There was no significant inhibitory effect on myeloperoxidase activity, requiring more specific analyses to assess this parameter. The results suggest that the CBD*bCD complexation is perfectly feasible, increasing its anti-edematogenic efficacy in the experimental model used.
PubDate: 2023-08-28
DOI: 10.1590/s2175-97902023e221000
Issue No: Vol. 59 (2023)
- Advancements in artificial intelligence and machine learning in
revolutionising biomarker discovery
Authors: Gokuldas (Vedant) Sarvesh Raikar, Amisha Sarvesh Raikar, Sandesh Narayan Somnache
Pages: 26 - 26
Abstract: O artigo explora a importância dos biomarcadores na pesquisa clínica e as vantagens da utilização de inteligência artificial (IA) e aprendizado de máquina (ML) no processo de descoberta. Os biomarcadores fornecem uma compreensão mais abrangente da progressão da doença e da resposta à terapia em comparação com os indicadores tradicionais. A IA e o ML oferecem uma nova abordagem para a descoberta de biomarcadores, aproveitando grandes quantidades de dados para identificar padrões e otimizar os biomarcadores existentes. Além disso, o artigo aborda o surgimento de biomarcadores digitais, que utilizam tecnologia para avaliar os estados fisiológicos e comportamentais de um indivíduo, e a importância do processamento adequado de dados ômicos e multiômicos para um manuseio eficiente por sistemas computacionais. No entanto, o artigo reconhece os desafios colocados pela IA/ML na identificação de biomarcadores, incluindo potenciais distorções nos dados e a necessidade de diversidade na representação dos dados. Para enfrentar esses desafios, o artigo sugere a importância da regulamentação e da diversidade no desenvolvimento de algoritmos de IA/ML.
PubDate: 2023-08-28
Issue No: Vol. 59 (2023)
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