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- Linalool: Therapeutic Indication And Their Multifaceted Biomedical
Applications-
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Authors: Singh; Shiva, Mishra, Anuradha Pages: 255 - 268 Abstract: This comprehensive review endeavors to illuminate the nuanced facets of linalool, a prominent monoterpene found abundantly in essential oils, constituting a massive portion of their composition. The biomedical relevance of linalool is a key focus, highlighting its therapeutic attributes observed through anti-nociceptive effects, anxiolytic properties, and behavioral modulation in individuals affected by dementia. These findings underscore the compound's potential application in biomedical applications. This review further explores contemporary formulations, delineating the adaptability of linalool in nano-emulsions, microemulsions, bio-capsules, and various topical formulations, including topical gels and lotions. This review covers published and granted patents between 2018–2024 and sheds light on the evolving landscape of linalool applications, revealing advancements in dermatological, anti-inflammatory, and antimicrobial domains. Citation: Drug Res (Stuttg) 2024; 74: 255-268 PubDate: 2024-07-05T08:50:30+01:00 DOI: 10.1055/a-2321-9571 Issue No: Vol. 74, No. 06 (2024)
- Bedaquiline: An Insight Into its Clinical Use in Multidrug-Resistant
Pulmonary Tuberculosis-
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Authors: Ahmad; Asad, Akhtar, Juber, Ahmad, Mohammad, Khan, Mohammad Irfan, Wasim, Rufaida, Islam, Anas, Singh, Aditya Pages: 269 - 279 Abstract: Every year, the World Health Organization reports 500,000 new cases of drug-resistant tuberculosis (TB), which poses a serious global danger. The increased number of XDR-TB and MDR-TB cases reported worldwide necessitates the use of new therapeutic approaches. The main issues with the antitubercular medications now in use for the treatment of multidrug-resistant tuberculosis are their poor side effect profile, reduced efficacy, and antimicrobial resistance. One possible remedy for these problems is bedaquiline. The need for better treatment strategies is highlighted by the strong minimum inhibitory concentrations that bedaquiline (BDQ), a novel anti-TB medicine, exhibits against both drug-resistant and drug-susceptible TB. Bedaquiline may be able to help with these problems. Bedaquiline is a medication that is first in its class and has a distinct and particular mode of action. Bedaquiline is an ATP synthase inhibitor that is specifically directed against Mycobacterium tuberculosis and some nontuberculous mycobacteria. It is metabolized by CYP3A4. Bedaquiline preclinical investigations revealed intralesional drug biodistribution. The precise intralesional and multi-compartment pharmacokinetics of bedaquiline were obtained using PET bioimaging and high-resolution autoradiography investigations. Reduced CFU counts were observed in another investigation after a 12-week course of therapy. Meta-analyses and systematic reviews of phase II trials on bedaquilineʼs efficacy in treating drug-resistant tuberculosis in patients reported higher rates of cure, better culture conversion, and lower death rates when taken in conjunction with a background regimen. Here is a thorough medication profile for bedaquiline to aid medical professionals in treating individuals with tuberculosis. Citation: Drug Res (Stuttg) 2024; 74: 269-279 PubDate: 2024-07-05T08:50:30+01:00 DOI: 10.1055/a-2331-7061 Issue No: Vol. 74, No. 06 (2024)
- Concomitant Effects of Metformin and Vitamin C on Indomethacin-Induced
Gastric Ulcer in Rats: Biochemical and Histopathological Approach-
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Authors: Khezri; Mohammad Rafi, Varzandeh, Reza, Ghasemnejad-Berenji, Morteza Pages: 280 - 289 Abstract: Introduction Gastric ulcer is one of the most common and serious conditions in the gastrointestinal tract. One of the main causes of gastric ulcers is using of non-steroidal anti-inflammatory drugs (NSAIDs) which have limited their use in clinical practice. Several studies have revealed that metformin and Vitamin C (Vit C) exhibit protective effects against gastric mucosal damage in different animal models. However, no studies indicate their combination's effect on gastric ulcer models. Therefore, this study aims to investigate the protective effects of metformin and Vit C combination on indomethacin-induced gastric ulcers. Material and methods In total, thirty rats were divided into six groups, including the control group, rats received indomethacin (50 mg/kg, i.p.), rats received indomethacin and pretreated with ranitidine (100 mg/kg), metformin (100 mg/kg, i.p.), Vit C (100 mg/kg), or metformin combined with Vit C. Four hours after indomethacin administration, rats were euthanized, and gastric tissues were removed for macroscopic, histopathologic, and biochemical examinations. Results All therapeutics used in this study were found to alleviate gastric mucosal injury caused by indomethacin, as observed in histopathologic and macroscopic evaluations. Both Vit C and metformin were observed to significantly decrease lipid peroxidation and enhance the activity of anti-oxidative enzymes, SOD, GPx, and catalase. However, a more significant effectiveness was observed in catalase and GPx activities when Vit C was co-administered with metformin. Conclusions In conclusion, the present study revealed that metformin and Vit C combination therapy could potentially treat gastric ulcers associated with indomethacin. Citation: Drug Res (Stuttg) 2024; 74: 280-289 PubDate: 2024-07-05T08:50:30+01:00 DOI: 10.1055/a-2317-7578 Issue No: Vol. 74, No. 06 (2024)
- Remdesivir-Related Cardiac Adverse Effects in COVID-19 Patients: A
Case-Control Study-
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Authors: Abedipour; Fatemah, Mirzaei, Hossein Hadavand, Ansari, Hossein, Ehsanzadeh, Neda, Rashki, Amin, Vahedi, Mohammad Mahdi, Rashki, Asma Pages: 290 - 295 Abstract: Background There have been reports of serious side effects of Remdesivir, including cardiovascular complications. The present study aimed to determine the adverse cardiovascular effects of Remdesivir and the factors affecting them in COVID-19 patients. Methods The patients were classified into two groups: those receiving Remdesivir without cardiac complications and those receiving Remdesivir with cardiovascular complications. After reviewing the patientʼs medical records, the relationship of some factors with the incidence of adverse cardiovascular effects was measured. Results Chi-square test showed that the distribution of complications in men was significantly higher than in women (P=0.001). The independent t-test revealed that the mean age in the group with complications was significantly higher than the group without complications (P=0.013). Fisherʼs exact test demonstrated a significant relationship between smoking and cardiovascular complications (P=0.05). According to the Mann-Whitney test, a significant difference was found in the mean changes of Bilirubin (P=0.02) and ALKP (P=0.01) before and after treatment in the groups with and without heart complications. Conclusion Our findings indicated that most of the COVID-19 patients suffered from sinus bradycardia, and the distribution of complications was more pronounced in men than in women. The mean age in the group with complications was higher than the group without complications. Smoking was found to be associated with the occurrence of cardiovascular complications and the mean changes of Bilirubin and ALKP before and after treatment were significantly different in the groups with and without cardiovascular complications. Citation: Drug Res (Stuttg) 2024; 74: 290-295 PubDate: 2024-07-05T08:50:29+01:00 DOI: 10.1055/a-2332-3253 Issue No: Vol. 74, No. 06 (2024)
- Exploring the Anticonvulsant Properties of a Celecoxib-Phospholipid
Conjugate: Synthesis, Activation, and Evaluation of Cytotoxicity-
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Authors: Anjali; Puthusserikkunnu B, Jawahar, Natarajan, Praharsh Kumar, Mandadhi R, Jubie, Selvaraj, Selvamuthukumar, Subramanian Pages: 296 - 301 Abstract: Background Epilepsy poses a significant global health challenge, particularly in regions with limited financial resources hindering access to treatment. Recent research highlights neuroinflammation, particularly involving cyclooxygenase-2 (COX-2) pathways, as a promising avenue for epilepsy management. Methods This study aimed to develop a Cyclooxygenase-2 inhibitor with potential anticonvulsant properties. A promising drug candidate was identified and chemically linked with phospholipids through docking analyses. The activation of this prodrug was assessed using phospholipase A2 (PLA2)-mediated hydrolysis studies. The conjugateʼs confirmation and cytotoxicity were evaluated using Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), and Sulphoramide B (SRB) assays. Results Docking studies revealed that the Celecoxib-Phospholipid conjugate exhibited a superior affinity for PLA2 compared to other drug-phospholipid conjugates. FT-IR spectroscopy confirmed the successful synthesis of the conjugate, while DSC analysis confirmed its purity and formation. PLA2-mediated hydrolysis experiments demonstrated selective activation of the prodrug depending on PLA2 concentration. SRB experiments indicated dose-dependent cytotoxic effects of Celecoxib, phospholipid non-toxicity, and efficient celecoxib-phospholipid conjugation. Conclusion This study successfully developed a Celecoxib-phospholipid conjugate with potential anticonvulsant properties. The prodrugʼs specific activation and cytotoxicity profile makes it a promising therapeutic candidate. Further investigation into underlying mechanisms and in vivo studies is necessary to assess its translational potential fully. Citation: Drug Res (Stuttg) 2024; 74: 296-301 PubDate: 2024-07-05T08:50:29+01:00 DOI: 10.1055/a-2331-7114 Issue No: Vol. 74, No. 06 (2024)
- Artificial Intelligence in Drug Identification and Validation: A Scoping
Review-
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Authors: Abubakar; Mukhtar Lawal, Kapoor, Neha, Sharma, Asha, Gambhir, Lokesh, Jasuja, Nakuleshwar Dutt, Sharma, Gaurav Pages: 208 - 219 Abstract: The end-to-end process in the discovery of drugs involves therapeutic candidate identification, validation of identified targets, identification of hit compound series, lead identification and optimization, characterization, and formulation and development. The process is lengthy, expensive, tedious, and inefficient, with a large attrition rate for novel drug discovery. Today, the pharmaceutical industry is focused on improving the drug discovery process. Finding and selecting acceptable drug candidates effectively can significantly impact the price and profitability of new medications. Aside from the cost, there is a need to reduce the end-to-end process time, limiting the number of experiments at various stages. To achieve this, artificial intelligence (AI) has been utilized at various stages of drug discovery. The present study aims to identify the recent work that has developed AI-based models at various stages of drug discovery, identify the stages that need more concern, present the taxonomy of AI methods in drug discovery, and provide research opportunities. From January 2016 to September 1, 2023, the study identified all publications that were cited in the electronic databases including Scopus, NCBI PubMed, MEDLINE, Anthropology Plus, Embase, APA PsycInfo, SOCIndex, and CINAHL. Utilising a standardized form, data were extracted, and presented possible research prospects based on the analysis of the extracted data. Citation: Drug Res (Stuttg) 2024; 74: 208-219 PubDate: 2024-06-03T13:00:30+01:00 DOI: 10.1055/a-2306-8311 Issue No: Vol. 74, No. 05 (2024)
- Discovery of Substituted 2-oxoquinolinylthiazolidin-4-one Analogues as
Potential EGFRK Inhibitors in Lung Cancer Treatment-
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Authors: Naik; Soniya, Soumya, Vasu, Mamledesai, Shivlingrao N, Manickavasagam, M, Choudhari, Prafulla, Rathod, Sanket Pages: 227 - 240 Abstract: Purpose Cancer is the second leading cause of death globally and is responsible for an estimated 9.6 million deaths in 2018. Globally, about 1 in 6 deaths is due to cancer and the chemotherapeutic drugs available have high toxicity and have reported side effects hence, there is a need for the synthesis of novel drugs in the treatment of cancer. Methods The current research work dealt with the synthesis of a series of 3-(3-acetyl-2-oxoquinolin-1-(2H)-yl-2-(substitutedphenyl)thiazolidin-4-one (Va-j) derivatives and evaluation of their in-vitro anticancer activity. All the synthesized compounds were satisfactorily characterized by IR and NMR data. Compounds were further evaluated for their in-vitro anticancer activity against A-549 (lung cancer) cell lines. The in-vitro anticancer activity was based upon the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay method. Results The synthesized compounds exhibited satisfactory anticancer properties against the A-549 cell line. The compound (Vh) showed the highest potency amongst the tested derivatives against the A-549 cell line with IC50 values of 100 µg/ml respectively and was also found to be more potent than Imatinib (150 µg/ml) which was used as a standard drug. Molecular docking studies of the titled compounds (Va-j) were carried out using AutoDock Vina/PyRx software. The synthesized compounds exhibited well-conserved hydrogen bonds with one or more amino acid residues in the active pocket of the EGFRK tyrosine kinase domain (PDB 1m17). Conclusion Among all the synthesized analogues, the binding affinity of the compound (Vh) was found to be higher than other synthesized derivatives and a molecular dynamics simulation study explored the stability of the docked complex system. Citation: Drug Res (Stuttg) 2024; 74: 227-240 PubDate: 2024-06-03T13:00:29+01:00 DOI: 10.1055/a-2305-2789 Issue No: Vol. 74, No. 05 (2024)
- Therapeutic Potential of Pentoxifylline in Paraquat-Induced Pulmonary
Toxicity: Role of the Phosphodiesterase Enzymes-
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Authors: Ghasemi; Farshad, Mohammadi, Mobina, Ghaffari, Fatemeh, Hosseini-Sharifabad, Ali, Omidifar, Navid, Nili-Ahmadabadi, Amir Pages: 241 - 249 Abstract: Pentoxifylline (PTX), a non-selective phosphodiesterase inhibitor, has demonstrated protective effects against lung injury in animal models. Given the significance of pulmonary toxicity resulting from paraquat (PQ) exposure, the present investigation was designed to explore the impact of PTX on PQ-induced pulmonary oxidative impairment in male mice.Following preliminary studies, thirty-six mice were divided into six groups. Group 1 received normal saline, group 2 received a single dose of PQ (20 mg/kg; i.p.), and group 3 received PTX (100 mg/kg/day; i.p.). Additionally, treatment groups 4–6 were received various doses of PTX (25, 50, and 100 mg/kg/day; respectively) one hour after a single dose of PQ. After 72 hours, the animals were sacrificed, and lung tissue was collected.PQ administration caused a significant decrease in hematocrit and an increase in blood potassium levels. Moreover, a notable increase was found in the lipid peroxidation (LPO), nitric oxide (NO), and myeloperoxidase (MPO) levels, along with a notable decrease in total thiol (TTM) and total antioxidant capacity (TAC) contents, catalase (CAT) and superoxide dismutase (SOD) enzymes activity in lung tissue. PTX demonstrated the ability to improve hematocrit levels; enhance SOD activity and TTM content; and decrease MPO activity, LPO and NO levels in PQ-induced pulmonary toxicity. Furthermore, these findings were well-correlated with the observed lung histopathological changes.In conclusion, our results suggest that the high dose of PTX may ameliorate lung injury by improving the oxidant/antioxidant balance in animals exposed to PQ. Citation: Drug Res (Stuttg) 2024; 74: 241-249 PubDate: 2024-06-03T13:00:30+01:00 DOI: 10.1055/a-2314-1137 Issue No: Vol. 74, No. 05 (2024)
- Assessing the Compatibility of Menatetrenone with Excipients: A
Spectroscopic Approach and Implication in Drug Formulation Development-
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Authors: Singh; Widhilika, Kushwaha, Poonam, Kushwaha, Shom Prakash Abstract: An experiment was conducted to evaluate the compatibility of menatetrenone with selected pharmaceutical excipients. Fourier Transform Infrared Spectroscopy (FTIR) was used to assess drug-excipient compatibility. The present research systematically investigates the FTIR spectrum of each chemical compound separately and their physical blends, analyzing for possible shifts, alterations or novel peak that may indicate chemical interactions. This study aims to utilize spectral data interpretation to detect potential compatibility problems that may occur while design and production of menatetrenone containing dosage forms ensuring their increased stability and effectiveness. The FTIR results demonstrated that all the pharmaceutical excipients were compatible with menatetrenone. In conclusion, the compatibility of pharmaceutical excipients with menatetrenone was successfully assessed using FTIR that will aid in future design of formulations containing menatetrenone as therapeutic moiety. Citation: Drug Res (Stuttg) ; : - PubDate: 2024-08-02T12:54:57+01:00 DOI: 10.1055/a-2361-2895
- Amputation Risk in Type II Diabetes Mellitus Patients Treated with SGLT-2
Inhibitors: A Systematic Literature Review of Randomized Clinical Trials-
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Authors: Hoda; Farazul, Jamali, Mohammad Chand, Arshad, Mawrah, Habib, Mohammad Anwar, Akhtar, Mohd, Najmi, Abul Kalam Abstract: Background SGLT-2 inhibitors, prescribed for type 2 diabetes, have a heightened risk of amputation. The FDA issued a warning in May 2017, leading to the inclusion of a cautionary label. Vigilance is essential for patients and healthcare providers to promptly identify and address potential limb complications associated with the use of SGLT-2 inhibitors. Method A comprehensive search of electronic databases was conducted, covering the period from inception to May 2024. This systematic literature review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was assessed using the Cochrane risk of bias (ROB) tool. Inclusion and exclusion criteria were predefined, and data extraction was performed to summarize the findings. Result A total of 12 randomized control trial (RCT) studies were included in the present systematic review. 37,657 (54.89%) participants were randomly assigned to receive the different interventions of SGLT-2 inhibitor, whereas 30,959 (45.11%) received a placebo. Overall, 618 events were reported in the treatment group, whereas 396 events were reported in the placebo group. Conclusion In conclusion, patients treated with SGLT-2 inhibitors did not have any significant difference in amputation occurrences compared to placebo across various studies. However, canagliflozin usage has led to higher amputation events in certain trials. Citation: Drug Res (Stuttg) ; : - PubDate: 2024-08-02T12:54:57+01:00 DOI: 10.1055/a-2366-8999
- Antibacterial Efficacy of Hiora: An Ayurvedic Mouthwash in Children
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Authors: Saha; Sonali, Kalita, Kongkana, Dhinsa, Kavita, Arora, Deval Kumar, Godhi, Brinda Suhas, Doddawad, Vidya Gowdappa Abstract: Background Mouthwashes, as a form of antimicrobial delivery system, rank among the safest and most effective vehicles, particularly in the case of young children. This is attributed to their ability to distribute therapeutic components across all accessible oral surfaces, including interproximal areas. Objective To evaluate the antibacterial efficacy of recently introduced Ayurvedic (Hiora) and triclosan-based mouthwashes among children. Materials and Methods A total of 45 healthy children aged 10–15 years were randomly assigned to three groups: Herbal mouthwash (Hiora), triclosan-based mouthwash (Kidodent), and normal saline as the control group. Saliva samples were collected pre-rinse, 2 minutes, 30 minutes, and 60 minutes post-rinsing with the study mouthwashes. These samples were then inoculated onto Petri dishes containing blood agar culture media, followed by incubation under both aerobic and anaerobic conditions at 37°C for 48 hours. The resulting bacterial colonies of Streptococcus spp. and Lactobacillus spp. were counted (CFU/ml x 105). Statistical analysis, including ANOVA, Newman Keul’s Post-hoc test, and a two-tailed ‘t’ test, was conducted to determine the significance of the results. Results The Ayurvedic Hiora mouthwash demonstrated the most substantial reduction in salivary bacterial colony counts of Streptococcus spp. and Lactobacillus spp. with statistically significant results (p Citation: Drug Res (Stuttg) ; : - PubDate: 2024-08-02T12:54:56+01:00 DOI: 10.1055/a-2368-4336
- Saliva Versus Plasma Therapeutic Drug Monitoring of Valproic Acid in
Jordanian Patients-
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Authors: Idkaidek; Nasir, Al-Tarawneh, Aya, Alshoaibi, Laith, Tuffaha, Haya, Zinati, Asma, Abdelqader, Majed, Al-Ghazawi, Ahmad, Rabayah, Ayman, Hamadi, Salim Abstract: Therapeutic drug monitoring is used to ensure that medications are prescribed and administered according to safe doseage advice and for the purpose of achieving the desired therapeutic effects in patients. Several methods are used to perform therapeutic drug monitoring. However, there is insufficient evidence to currently support therapeutic drug monitoring of Valproic acid using salivary samples. The aim of this paper is to determine the feasibility of using salivary samples as a substitute for plasma samples for therapeutic drug monitoring of Valproic acid. In this study a total of 23 patients participated, with the mean age of 33.39. Salivary and plasma samples were collected and analysed to determine the peak and trough concentrations of Valproic acid for comparison between the two methods. Calibrated LC- MS/ MS was used to measure Valproic acid levels. Statistical analyses were performed using ANOVA test and ethical approval was obtained prior to sample collection. The results showed that saliva Valproic acid levels were less than that of plasma levels. There was no significant correlation between saliva and plasma level of Valproic acid (P>0.05). However, there was a significant correlation between the area under the curve for both saliva and plasma Valproic acid (P Citation: Drug Res (Stuttg) ; : - PubDate: 2024-07-19T18:15:15+01:00 DOI: 10.1055/a-2357-8095
- Cerebroprotective Potential of Andrographolide Nanoparticles: In silico
and In vivo Investigations-
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Authors: Rudrala; Lakshmi Charitha, Challa, Ranadheer Reddy, Subramanyam, Sibbala, Ayyappa Gouru, Sampath, Singh, Gagandeep, Sirisha Mulukuri, N.V. L., Pasala, Praveen Kumar, Dintakurthi, Prasanth Sree Naga Bala Krishna, Gajula, Somasekhar, Rudrapal, Mithun Abstract: Ischemic stroke remains the leading cause of death and disability, while the main mechanisms of dominant neurological damage in stroke contain oxidative stress and inflammation. Docking studies revealed a binding energy of − 6.1 kcal/mol for AG, while the co-crystallized ligand (CCl) exhibited a binding energy of − 7.3 kcal/mol with NOS. AG demonstrated favourable hydrogen bond interactions with amino acids ASN A:354 and ARG A:388 and hydrophobic interactions with GLU A:377. Molecular dynamics simulations throughout 100 ns indicated a binding affinity of − 27.65±2.88 kcal/mol for AG, compared to − 18.01±4.02 kcal/mol for CCl. These findings suggest that AG possesses a superior binding affinity for NOS compared to CCl, thus complementing the stability of NOS at the docked site.AG has limited applications owing to its low bioavailability, poor water solubility, and high chemical and metabolic instability.The fabrication method was employed in the preparation of AGNP, SEM analysis confirmed spherical shape with size in 19.4±5 nm and investigated the neuroprotective effect in cerebral stroke rats induced by 30 min of carotid artery occlusion followed by 4 hr reperfusion, evaluated by infarction size, ROS/RNS via GSH, MPO, NO estimationand AchE activity, and monitoring EEG function. Cortex and hippocampal histology were compared between groups. AGNP treatment significantly decreased Infarction size and increased GSH levels (p Citation: Drug Res (Stuttg) ; : - PubDate: 2024-07-11T11:18:45+01:00 DOI: 10.1055/a-2345-5396
- Genito Urinary Infection and Urinary Tract Infection in Patients with Type
2 Diabetes Mellitus Receiving SGLT2 Inhibitors: Evidence from a Systematic Literature Review of Landmark Randomized Clinical Trial-
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Authors: Arshad; Mawrah, Hoda, Farazul, Siddiqui, Nasir Ali, Najmi, Abul Kalam, Ahmad, Mohammad Abstract: Background and purpose SGLT2 inhibitors are class of drugs that are used in adults with type 2 diabetes through a novel mechanism of action by reducing renal tubular glucose reabsorption, leading to a reduction in blood glucose without stimulating insulin release. In this systematic review, we report the effects of treatment with SGLT2 inhibitors on urinary tract infection (UTI) and genitourinary infection (GUI). Method The study integrated data from landmark trials of SGLT2 inhibitors (CANVAS, CREDENCE, DECLARE–TIMI 58, and EMPA-REG) to interpret the association of SGLT2 inhibitors with genital infection (GI) and UTI. We reported the review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome was a composite of participants reporting UTI and GUI prescribed on SGLT2 inhibitors. Results The analysis of four studies involving 38,723 participants revealed incidences of both UTIs and GUI. In the SGLT2 inhibitor group, comprising 21,266 participants, 222 (1.04%) experienced UTIs, and 477 (2.24%) reported GUI. In contrast, among the placebo group consisting of 17,457 participants, 201 (1.15%) reported UTIs, and 70 (0.40%) reported genital infections. These findings underscore the elevated risk associated with SGLT2 inhibitor use, particularly regarding GUI, necessitating careful consideration in clinical practice and patient management strategies. Conclusion The incidence of UTIs and particularly more pronounced GUI associated with SGLT2 inhibitors highlights the importance of careful risk assessment and monitoring in clinical decision-making, underscoring the need for patient management strategies. Citation: Drug Res (Stuttg) ; : - PubDate: 2024-07-11T07:55:43+01:00 DOI: 10.1055/a-2347-9824
- HIF Stabilizer Desidustat Protects against Complement-Mediated Diseases
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Authors: Patel; Vishal J., Joharapurkar, Amit A., Kshirsagar, Samadhan G., Patel, Maulik S., Savsani, Hardikkumar H., Dodiya, Harshad S., Rakhasiya, Milan H., Patel, Ashvin K., Sundar, Rajesh, Jain, Mukul R. Abstract: Complement cascade is a defence mechanism useful for eliminating pathogenic microorganisms and damaged cells. However, activation of alternative complement system can also cause inflammation and promote kidney and retinal disease progression. Inflammation causes tissue hypoxia, which induces hypoxia-inducible factor (HIF) and HIF helps the body to adapt to inflammation. In this study, we investigated the effect of HIF stabilizer desidustat in complement-mediated diseases. Oral administration of desidustat (15 mg/kg) was effective to reduce the kidney injury in mice that was induced by either lipopolysaccharide (LPS), doxorubicin or bovine serum albumin (BSA)-overload. Complement activation-induced membrane attack complex (MAC) formation and factor B activity were also reduced by desidustat treatment. In addition, desidustat was effective against membranous nephropathy caused by cationic BSA and retinal degeneration induced by sodium iodate in mice. C3-deposition, proteinuria, malondialdehyde, and interleukin-1ß were decreased and superoxide dismutase was increased by desidustat treatment in cBSA-induced membranous nephropathy. Desidustat specifically inhibited alternative complement system, without affecting the lectin-, or classical complement pathway. This effect appears to be mediated by inhibition of factor B. These data demonstrate the potential therapeutic value of HIF stabilization by desidustat in treatment of complement-mediated diseases. Citation: Drug Res (Stuttg) ; : - PubDate: 2024-07-11T07:55:42+01:00 DOI: 10.1055/a-2347-9919
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