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- Medicines, Vol. 12, Pages 2: Hypomyelinating Leukodystrophy 14
(HLD14)-Related UFC1 p.Arg23Gln Decreases Cell Morphogenesis: A Phenotype
Reversable with Hesperetin
Authors: Yuri Ichihara, Maho Okawa, Minori Minegishi, Hiroaki Oizumi, Masahiro Yamamoto, Katsuya Ohbuchi, Yuki Miyamoto, Junji Yamauchi
First page: 2
Abstract: Introduction: In the central nervous system (CNS), proper interaction between neuronal and glial cells is crucial for the development of mature nervous tissue. Hypomyelinating leukodystrophies (HLDs) are a group of genetic CNS disorders characterized by hypomyelination and/or demyelination. In these conditions, genetic mutations disrupt the biological functions of oligodendroglial cells, which are responsible for wrapping neuronal axons with myelin sheaths. Among these, an amino acid mutation of the ubiquitin-fold modifier conjugating enzyme 1 (UFC1) is associated with HLD14-related disease, characterized by hypomyelination and delayed myelination in the brain. UFC1 is a critical component of the UFMylation system, functioning similarly to E2-conjugating enzymes in the ubiquitin-dependent protein degradation system. Methodology: We describe how a missense mutation in UFC1 (p.Arg23Gln) leads to the aggregation of UFC1 primarily in lysosomes in FBD-102b cells, which are undergoing oligodendroglial cell differentiation. Results: Cells with mutated UFC1 exhibit reduced Akt kinase phosphorylation and reduced expression of differentiation and myelination marker proteins. Consistently, these cells exhibit impaired morphological differentiation with a reduced ability to extend widespread membranes. Interestingly, hesperetin, a citrus flavonoid with known neuroprotective properties, was found to restore differentiation abilities in cells with the UFC1 mutation. Conclusions: These findings indicate that the HLD14-related mutation in UFC1 causes its lysosomal aggregation, impairing its morphological differentiation. Furthermore, the study highlights potential therapeutic insights into the pathological molecular and cellular mechanisms underlying HLD14 and suggests hesperetin as a promising candidate for treatment.
Citation: Medicines
PubDate: 2025-01-16
DOI: 10.3390/medicines12010002
Issue No: Vol. 12, No. 1 (2025)
- Medicines, Vol. 12, Pages 3: Thrombosed Mechanical Aortic Valve Treated
with Low-Dose Ultraslow Alteplase Infusion
Authors: Nicholas Pavlatos, Pawan Daga, Aangi Shah, Muhammad Khan, Jishanth Mattumpuram
First page: 3
Abstract: Background: Prosthetic valve thrombosis is a rare but serious complication of mechanical valve replacement. Traditionally, prosthetic valve thrombosis has been managed by surgical intervention; however, there is increasing data to support the use of thrombolytics. Methods: We present a case of a 74-year-old female with a history of rheumatic fever and subsequent mechanical aortic valve replacement on warfarin who presented to the emergency department with disequilibrium and chest pain. Results: She was found to have a subtherapeutic international normalized ratio and thrombosed mechanical aortic valve seen on transthoracic echocardiography, transesophageal echocardiography, and fluoroscopy. Conclusions: She was treated with a low-dose ultraslow alteplase infusion of 25 mg of alteplase administered over 25 h. Post-infusion transthoracic echocardiography immediately following infusion and four months later confirmed resolution of thrombosis.
Citation: Medicines
PubDate: 2025-02-02
DOI: 10.3390/medicines12010003
Issue No: Vol. 12, No. 1 (2025)
- Medicines, Vol. 12, Pages 4: Beyond the Needle: Innovative
Microneedle-Based Transdermal Vaccination
Authors: Hiep X. Nguyen
First page: 4
Abstract: Vaccination represents a critical preventive strategy in the current global healthcare system, serving as an indispensable intervention against diverse pathogenic threats. Although conventional immunization relies predominantly on hypodermic needle-based administration, this method carries substantial limitations, including needle-associated fear, bloodborne pathogen transmission risks, occupational injuries among healthcare workers, waste management issues, and dependence on trained medical personnel. Microneedle technology has emerged as an innovative vaccine delivery system, offering convenient, effective, and minimally invasive administration. These microscale needle devices facilitate targeted antigen delivery to epidermal and dermal tissues, where abundant populations of antigen-presenting cells, specifically Langerhans and dermal dendritic cells, provide robust immunological responses. Multiple research groups have extensively investigated microneedle-based vaccination strategies. This transdermal delivery technique offers several advantages, notably circumventing cold-chain requirements and enabling self-administration. Numerous preclinical investigations and clinical trials have demonstrated the safety profile, immunogenicity, and patient acceptance of microneedle-mediated vaccine delivery across diverse immunization applications. This comprehensive review examines the fundamental aspects of microneedle-based immunization, including vaccination principles, transcutaneous immunization strategies, and microneedle-based transdermal delivery—including classifications, advantages, and barriers. Furthermore, this review addresses critical technical considerations, such as treatment efficacy, application methodologies, wear duration, dimensional optimization, manufacturing processes, regulatory frameworks, and sustainability considerations, followed by an analysis of the future perspective of this technology.
Citation: Medicines
PubDate: 2025-02-07
DOI: 10.3390/medicines12010004
Issue No: Vol. 12, No. 1 (2025)
- Medicines, Vol. 12, Pages 5: Justice for Placebo: Placebo Effect in
Clinical Trials and Everyday Practice
Authors: Nebojsa Nick Knezevic, Aleksandar Sic, Samantha Worobey, Emilija Knezevic
First page: 5
Abstract: The placebo effect has been widely documented across various medical conditions, demonstrating its ability to influence both subjective and objective outcomes. Placebo responses can significantly improve symptoms in these different conditions, such as pain, Parkinson’s disease, depression, anxiety, and addiction. Psychological mechanisms, particularly the power of patient expectations, appear to play a central role, with neurobiological evidence supporting the activation of dopamine, endogenous opioids, and endocannabinoids in response to placebo interventions. Studies have demonstrated that placebo injections and more complex procedures, including sham surgeries, can produce therapeutic effects comparable to real treatments, particularly in pain management and neurological disorders. Moreover, placebo responses could be amplified when patients are aware of receiving treatment, as shown by research on open-label placebos and open versus hidden medical treatments. The effectiveness of 0.9% sodium chloride solution as a placebo in clinical trials is debated, with some studies indicating its potential to induce clinical improvements, though it may not be an ideal control in inflammatory pain conditions. Advances in neuroimaging have revealed that placebo treatments trigger tangible biological processes in the brain and body and are supported by psychological and physiological mechanisms that interact, suggesting real biological processes are involved in the observed effects. Overall, the growing understanding of placebo mechanisms suggests that incorporating placebo-based strategies, with patient awareness and appropriate ethical considerations, may offer significant potential for improving patient outcomes, particularly in chronic pain, mental health, and neurological conditions.
Citation: Medicines
PubDate: 2025-02-24
DOI: 10.3390/medicines12010005
Issue No: Vol. 12, No. 1 (2025)
- Medicines, Vol. 12, Pages 6: New Synthetic Compounds with Psychoactive
Action—Preliminary Results Among Primary and High School Students on
the Territory of Novi Sad
Authors: Igor Kelečević, Ljubica Gugleta, Ana-Marija Vejnović, Vesna Mijatović Jovin
First page: 6
Abstract: Introduction: Novel psychoactive substances (NPSs) are substances not controlled by the United Nations’ 1961 Narcotic Drugs and 1971 Psychotropic Substances convention, which pose a threat to public health. The use of NPSs is growing among recreational drug users. NPSs mimic the effects of the existing illegal drugs; they are used as substitutes for the traditional drugs of use. NPSs are commonly marketed as safe substances. NPS abuse is especially risky among vulnerable individuals, such as children and adolescents. The Aim: This study aims to analyze the knowledge and attitudes of primary and high school students regarding NPSs, determining the frequency and patterns of NPS use, and examine motivational factors for their consumption. Methodology: The questionnaire was employed to primary and secondary school students of the city of Novi Sad in November 2024. The data were analyzed using the methods of descriptive and inferential statistics in the statistical software package JASP 0.18.1.0. Results: A total of 1095 participants took part in the survey (53.6% males and 46.4% females). The age range of participants was 11–18 years (mean age 14.637 years). The majority of pupils lived in the city (70.5%). The most numerous students were students with the highest overall grade. The proportion of students who were familiar with NPSs was 38.3%, while 61.7% of them were not aware of their existence. Living in cities correlated positively with the NPS knowledge. The NPS risk awareness was notably low. The proportion of students who tried one or more novel drugs was 1.918%. Conclusions: The abuse of novel psychoactive substances is a growing concern, particularly among young individuals, requiring increased awareness and education on their risks. Educational systems should provide accurate information to prevent false beliefs, while policymakers must legally regulate new drugs. A coordinated approach is crucial for effective prevention, involving education, media, and support from different organizations. Future studies should focus on the impact of education on attitudes towards NPSs.
Citation: Medicines
PubDate: 2025-03-14
DOI: 10.3390/medicines12010006
Issue No: Vol. 12, No. 1 (2025)
- Medicines, Vol. 12, Pages 1: The Pharmacokinetic Changes in Cystic
Fibrosis Patients Population: Narrative Review
Authors: Ayda Awaness, Rania Elkeeb, Sepehr Afshari, Eman Atef
First page: 1
Abstract: Cystic fibrosis (CF) is a rare genetic disorder commonly affecting multiple organs such as the lungs, pancreas, liver, kidney, and intestine. Our search focuses on the pathophysiological changes that affect the drugs’ absorption, distribution, metabolism, and excretion (ADME). This review aims to identify the ADME data that compares the pharmacokinetics (PK) of different drugs in CF and healthy subjects. The published data highlight multiple factors that affect absorption, such as the bile salt precipitation and the gastrointestinal pH. Changes in CF patients’ protein binding and body composition affected the drug distribution. The paper also discusses the factors affecting metabolism and renal elimination, such as drug–protein binding and metabolizing enzyme capacity. The majority of CF patients are on multidrug therapy, which increases the risk of drug–drug interactions (DDI). This is particularly true for those receiving the newly developed transmembrane conductance regulator (CFTR), as they are at a higher risk for CYP-related DDI. Our research highlights the importance of meticulously evaluating PK variations and DDIs in drug development and the therapeutic management of CF patients.
Citation: Medicines
PubDate: 2024-12-31
DOI: 10.3390/medicines12010001
Issue No: Vol. 12, No. 1 (2024)
- Medicines, Vol. 11, Pages 19: Does Ortho-Substitution Enhance Cytotoxic
Potencies in a Series of 3,5-Bis(benzylidene)-4-piperidones'
Authors: Subhas S. Karki, Umashankar Das, Jan Balzarini, Erik De Clercq, Hiroshi Sakagami, Yoshihiro Uesawa, Praveen K. Roayapalley, Jonathan R. Dimmock
First page: 19
Abstract: Background: A series of 3,5-benzylidene-4-piperidones, 1a–n, were prepared to evaluate the hypothesis that the placement of different groups in the ortho-location of the aryl rings led to compounds with greater cytotoxic potencies than structural analogs. Methods: The bioevaluation of 1a–n was undertaken using human Molt/4C8 and CEM cells as well as murine L1210 cells. Correlations were sought between the interplanar angles θA and θB and the cytotoxic potencies. A QSAR analysis was also undertaken. In order to evaluate whether these compounds demonstrated greater toxicity to neoplasms than non-malignant cells, 1a–n were evaluated against HSC-2, HSC-3, HSC-4 and HL60 neoplasms as well as non-malignant HGF, HPC and HPLF cells. Results: A positive correlation was noted between the interplanar angle θA of one of the aryl rings and the adjacent olefinic linkage with IC50 values in the Molt4/C8 screens. The QSAR analysis revealed a positive correlation between the Hansch pi (π) value of the aryl substituents and the IC50 values of the compounds towards the Molt4/C8 and CEM cells. The dienones in series 1 demonstrated higher tumor-selective toxicity towards HSC-2, HSC-3, HSC-4 and HL-60 neoplasms than HGF, HPC and HPLF cells. Conclusions: The bioevaluations revealed some support for greater cytotoxic potencies to be displayed by compounds having ortho-substituents.
Citation: Medicines
PubDate: 2024-10-30
DOI: 10.3390/medicines11080019
Issue No: Vol. 11, No. 8 (2024)
- Medicines, Vol. 11, Pages 20: Safety Implications of Off-Label Medication
Use in Athletes: A Narrative Review
Authors: Silva, Madeira, Joaquim, Matos
First page: 20
Abstract: In recent years, the off-label use of medications in sports has increased significantly, primarily driven by psychological and social factors. Athletes frequently misuse drugs without adequate medical supervision, relying on unreliable sources of information, which leads to improper usage and serious health risks. This narrative review analyzes literature from PubMed® (Medline), Scopus®, and Web of Science® databases, focusing on studies up to December 2023, to examine the safety concerns related to off-label drug use in sports. The review presents an overview of the off-label use of pharmacological substances by athletes, focusing on both hormonal and non-hormonal drugs. Hormonal substances such as anabolic steroids and growth hormones, and non-hormonal agents like diuretics and β2-agonists, are frequently abused. These practices are associated with severe side effects, including infections, cardiovascular complications, hormonal imbalances, psychological disorders, dependence, and even cases of death. The study emphasizes the need for stronger regulation, public awareness initiatives, and preventive strategies to mitigate the health risks associated with this growing trend.
Citation: Medicines
PubDate: 2024-11-15
DOI: 10.3390/medicines11080020
Issue No: Vol. 11, No. 8 (2024)
- Medicines, Vol. 11, Pages 21: Utility of Aprepitant in the Management of
Pediatric Patients with Cyclical Vomiting Syndrome
Authors: Aravind Thavamani, Sindhoosha Malay, Jasmine Khatana, Sujithra Velayuthan, Senthilkumar Sankararaman
First page: 21
Abstract: Introduction: Cyclical vomiting syndrome (CVS) is a recurrent debilitating illness characterized by intense episodes of nausea and emesis with widely varied pharmacological management across the country. Aprepitant is now increasingly used in patients with CVS. The impact of aprepitant as an abortive therapy in the readmission of pediatric patients with CVS is currently unknown. Methodology: We analyzed all pediatric patients with a primary diagnosis of CVS using the ICD-10 code in the Pediatric Health Information System database of the Children’s Hospital Association. We evaluated the demographic data, comorbid conditions, and management details during the inpatient stay. CVS patients who received aprepitant during their inpatient hospitalization were compared with patients without aprepitant use. Seven-day readmission rate for CVS was used as the outcome variable to assess the effectiveness of the aprepitant in aborting an episode. Propensity score matching was used to match the two cohorts. Results: We analyzed 1775 patients of which 96 received aprepitant during the inpatient hospitalization. The aprepitant group had a more severe hospitalization course as evidenced by an increased duration of hospital stay (5 vs. 3 days) and total hospitalization costs ($11,790 vs. $6380). There were no significant differences in the 7-day (17% vs. 16%, p = 0.91) readmission rate and results were not altered by propensity score matching. Conclusions: Aprepitant use as an abortive therapy did not affect the 7-day CVS-related readmission rate. Further prospective studies are needed to explore the role of aprepitant as an abortive agent in the management of CVS in the pediatric population.
Citation: Medicines
PubDate: 2024-12-11
DOI: 10.3390/medicines11080021
Issue No: Vol. 11, No. 8 (2024)
- Medicines, Vol. 11, Pages 22: RETRACTED: Zulfiqar et al. Obesity and
Frailty Syndrome in the Elderly: Prospective Study in Primary Care.
Medicines 2022, 9, 38
Authors: Abrar-Ahmad Zulfiqar, Perla Habchi, Ibrahima Amadou Dembele
First page: 22
Abstract: The journal retracts the article titled “Obesity and Frailty Syndrome in the Elderly: Prospective Study in Primary Care” [...]
Citation: Medicines
PubDate: 2024-12-18
DOI: 10.3390/medicines11080022
Issue No: Vol. 11, No. 8 (2024)
- Medicines, Vol. 11, Pages 14: Cytokine Storm in COVID-19: Insight into
Pathological Mechanisms and Therapeutic Benefits of Chinese Herbal
Medicines
Authors: Qingyuan Yu, Xian Zhou, Rotina Kapini, Anthony Arsecularatne, Wenting Song, Chunguang Li, Yang Liu, Junguo Ren, Gerald Münch, Jianxun Liu, Dennis Chang
First page: 14
Abstract: Cytokine storm (CS) is the main driver of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) in severe coronavirus disease-19 (COVID-19). The pathological mechanisms of CS are quite complex and involve multiple critical molecular targets that turn self-limited and mild COVID-19 into a severe and life-threatening concern. At present, vaccines are strongly recommended as safe and effective treatments for preventing serious illness or death from COVID-19. However, effective treatment options are still lacking for people who are at the most risk or hospitalized with severe disease. Chinese herbal medicines have been shown to improve the clinical outcomes of mild to severe COVID-19 as an adjunct therapy, particular preventing the development of mild to severe ARDS. This review illustrates in detail the pathogenesis of CS-involved ARDS and its associated key molecular targets, cytokines and signalling pathways. The therapeutic targets were identified particularly in relation to the turning points of the development of COVID-19, from mild symptoms to severe ARDS. Preclinical and clinical studies were reviewed for the effects of Chinese herbal medicines together with conventional therapies in reducing ARDS symptoms and addressing critical therapeutic targets associated with CS. Multiple herbal formulations, herbal extracts and single bioactive phytochemicals with or without conventional therapies demonstrated strong anti-CS effects through multiple mechanisms. However, evidence from larger, well-designed clinical trials is lacking and their detailed mechanisms of action are yet to be well elucidated. More research is warranted to further evaluate the therapeutic value of Chinese herbal medicine for CS in COVID-19-induced ARDS.
Citation: Medicines
PubDate: 2024-07-18
DOI: 10.3390/medicines11070014
Issue No: Vol. 11, No. 7 (2024)
- Medicines, Vol. 11, Pages 15: Deciphering Mechanisms, Prevention
Strategies, Management Plans, Medications, and Research Techniques for
Strokes in Systemic Lupus Erythematosus
Authors: Ola A. Al-Ewaidat, Moawiah M. Naffaa
First page: 15
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune rheumatic condition characterized by an unpredictable course and a wide spectrum of manifestations varying in severity. Individuals with SLE are at an increased risk of cerebrovascular events, particularly strokes. These strokes manifest with a diverse range of symptoms that cannot be solely attributed to conventional risk factors, underscoring their significance among the atypical risk factors in the context of SLE. This complexity complicates the identification of optimal management plans and the selection of medication combinations for individual patients. This susceptibility is further complicated by the nuances of neuropsychiatric SLE, which reveals a diverse array of neurological symptoms, particularly those associated with ischemic and hemorrhagic strokes. Given the broad range of clinical presentations and associated risks linking strokes to SLE, ongoing research and comprehensive care strategies are essential. These efforts are critical for improving patient outcomes by optimizing management strategies and discovering new medications. This review aims to elucidate the pathological connection between SLE and strokes by examining neurological manifestations, risk factors, mechanisms, prediction and prevention strategies, management plans, and available research tools and animal models. It seeks to explore this medical correlation and discover new medication options that can be tailored to individual SLE patients at risk of stroke.
Citation: Medicines
PubDate: 2024-07-31
DOI: 10.3390/medicines11070015
Issue No: Vol. 11, No. 7 (2024)
- Medicines, Vol. 11, Pages 16: Postoperative Nausea and Vomiting in the
Ambulatory Surgery Center: A Narrative Review
Authors: Justin Bell, Adam Bindelglass, Jennifer Morrone, Sherwin Park, Ana Costa, Sergio Bergese
First page: 16
Abstract: Postoperative nausea and vomiting (PONV) is a common complication of ambulatory surgery, leading to numerous deleterious effects such as decreased patient satisfaction, prolonged recovery unit stays, and rarely, more serious complications such as aspiration pneumonia or wound dehiscence. In this paper, we present a narrative review of the literature regarding common risk factors for PONV including patient factors, surgical factors, and anesthetic factors. We then will review anesthetic techniques and antiemetic drugs demonstrated to mitigate the risk of PONV. Finally, we discuss the potential economic benefits of PONV prophylaxis in the perioperative ambulatory setting.
Citation: Medicines
PubDate: 2024-08-09
DOI: 10.3390/medicines11070016
Issue No: Vol. 11, No. 7 (2024)
- Medicines, Vol. 11, Pages 17: GDF15 Targeting for Treatment of Hyperemesis
Gravidarum
Authors: Jamie Thygerson, Dallin Oyler, Jackson Thomas, Brandon Muse, Benjamin D. Brooks, Jessica E. Pullan
First page: 17
Abstract: Nausea and vomiting during pregnancy (NVP), particularly its severe form, Hyperemesis gravidarum (HG), affects up to 70% of pregnancies and significantly impacts the quality of life for those with the condition as well as generates a great economic burden, with annual costs exceeding $1.7 billion in the United States. Despite the available treatments targeting neurotransmitters like serotonin and dopamine, many patients experience inadequate relief and suffer from severe side effects, including headaches and dizziness. Recent research has underscored the role of GDF15, a protein mainly produced by the placenta and linked to NVP symptoms. This protein, part of the TGF-β superfamily, has been implicated in appetite and weight regulation and is altered in those with HG due to specific genetic mutations. Addressing the challenges of delivering effective treatments, current innovations focus on targeting GDF15 to reduce symptoms while ensuring fetal safety. Promising therapeutic strategies include non-IgG immunotherapies, small peptide and molecule antagonists, and novel administration methods such as transdermal patches. These approaches aim to optimize dosage and reduce adverse effects. The effective development and testing of these treatments necessitate advanced animal models that closely resemble human pregnancy physiology, highlighting the need for further research and funding. This ongoing research holds significant potential to improve the clinical outcomes for HG patients and decrease the economic impact on healthcare systems, urging a dedicated response from the scientific and medical communities to advance these promising treatments.
Citation: Medicines
PubDate: 2024-08-30
DOI: 10.3390/medicines11070017
Issue No: Vol. 11, No. 7 (2024)
- Medicines, Vol. 11, Pages 18: Breathing for Two: Asthma Management,
Treatment, and Safety of Pharmacological Therapy during Pregnancy
Authors: Jovan Javorac, Dejan Živanović, Biljana Zvezdin, Vesna Mijatović Jovin
First page: 18
Abstract: The primary objectives of asthma management during pregnancy are to achieve adequate symptom control, reduce the risk of acute exacerbations, and maintain normal pulmonary function, all of which contribute to ensuring the health and well-being of both the mother and the baby. The Global Initiative for Asthma (GINA) recommends that pregnant women with asthma continue using asthma medications throughout pregnancy, as the benefits of well-controlled asthma for both the mother and fetus outweigh the potential risks of medication side effects, poorly controlled asthma, and exacerbations. The classification of asthma medications by the US Food and Drug Administration (FDA) into categories A, B, C, D, and X is no longer applied. Instead, the potential benefits and risks of each medication during pregnancy and lactation are considered individually. The use of medications to achieve good asthma control and prevent exacerbations during pregnancy is justified, encompassing inhaled corticosteroids (ICS), some leukotriene receptor antagonists (LTRA), short-acting beta-2 agonists (SABA), long-acting beta-2 agonists (LABA), short-acting muscarinic antagonists (SAMA), long-acting muscarinic antagonists (LAMA), and, recently, biological therapies, even in the absence of definitive safety data during pregnancy.
Citation: Medicines
PubDate: 2024-09-05
DOI: 10.3390/medicines11070018
Issue No: Vol. 11, No. 7 (2024)
- Medicines, Vol. 11, Pages 12: Incidence and Outcomes of COVID-19 Vaccine
Hypersensitivity Reactions and Success of COVID-19 Vaccine Provocation
Tests Post Previous COVID-19 Vaccine Hypersensitivity
Authors: Adi Kurniawan, Sukamto Koesnoe, Evy Yunihastuti, Hamzah Shatri
First page: 12
Abstract: Background: The COVID-19 pandemic has led to high mortality rates. There have been reports of hypersensitivity reactions with mild to severe symptoms. The COVID-19 vaccine provocation test is a vaccination protocol for individuals with a history of hypersensitivity. This study aims to determine the benefits of COVID-19 vaccine provocation tests in patients with a history of hypersensitivity reactions to COVID-19 vaccines and its influencing factors. Objective: To determine the incidence, severity, outcome of hypersensitivity reactions, and success of the COVID-19 vaccine provocation test. Methods: A retrospective cohort study was conducted, using subjects taken from medical record data at the RSCM who had received COVID-19 vaccination with a history of hypersensitivity. Data was taken from the COVID-19 vaccination records at the RSCM, BPJS Health Primary Care application. Results: From a total of 29,036 doses of the COVID-19 vaccine, 44 patients experienced hypersensitivity reactions. As many as 38.64% did not continue vaccination, 2.27% experienced mild hypersensitivity, and 59.44% were successfully vaccinated. Conclusions: People with a history of hypersensitivity reactions to COVID-19 vaccines can still receive subsequent COVID-19 vaccinations at healthcare facilities equipped with anaphylaxis kits and immunology allergists.
Citation: Medicines
PubDate: 2024-05-27
DOI: 10.3390/medicines11060012
Issue No: Vol. 11, No. 6 (2024)
- Medicines, Vol. 11, Pages 13: An Unusual Case of Immune Complex-Mediated
Membranoproliferative Glomerulonephritis as Renal Manifestation of
Idiopathic Hypereosinophilic Syndrome: A Case Report and Literature Review
Authors: Michael Cieza-Terrones, José C. De La De La Flor, Christian Requejo, Daniel Villa, Jacqueline Apaza, Pablo Rodríguez-Doyágüez, Rocío Zamora, Carmen Asato-Higa, David Rivera-Estrella, Antonio Carrasco-Yalán
First page: 13
Abstract: Background: Idiopathic hypereosinophilic syndrome (IHES) is a disorder characterized by abnormal and persistent peripheral blood hypereosinophilia (eosinophil count ≥ 1.5× 109/L and ≥10% eosinophils) with duration ≥ 6 months, associated organ damage, and/or dysfunction attributable to tissue eosinophilic infiltrate of unknown cause. IHES affects different organs such as the heart, lungs, nervous system, and skin, with renal involvement being rare in this condition. Case Presentation: We present a case of a young patient with IHES and immune complex-mediated membranoproliferative glomerulonephritis with nephrotic syndrome, as a rare renal manifestation. We discuss the clinical, analytical, and histopathologic renal and hematologic features, comparing them with other reported cases in the literature.
Citation: Medicines
PubDate: 2024-06-02
DOI: 10.3390/medicines11060013
Issue No: Vol. 11, No. 6 (2024)
- Medicines, Vol. 11, Pages 10: A Modern Approach to the Treatment of
Traumatic Brain Injury
Authors: Marat Syzdykbayev, Maksut Kazymov, Marat Aubakirov, Aigul Kurmangazina, Ernar Kairkhanov, Rustem Kazangapov, Zhanna Bryzhakhina, Saule Imangazinova, Anton Sheinin
First page: 10
Abstract: Background: Traumatic brain injury manifests itself in various forms, ranging from mild impairment of consciousness to severe coma and death. Traumatic brain injury remains one of the leading causes of morbidity and mortality. Currently, there is no therapy to reverse the effects associated with traumatic brain injury. New neuroprotective treatments for severe traumatic brain injury have not achieved significant clinical success. Methods: A literature review was performed to summarize the recent interdisciplinary findings on management of traumatic brain injury from both clinical and experimental perspective. Results: In the present review, we discuss the concepts of traditional and new approaches to treatment of traumatic brain injury. The recent development of different drug delivery approaches to the central nervous system is also discussed. Conclusions: The management of traumatic brain injury could be aimed either at the pathological mechanisms initiating the secondary brain injury or alleviating the symptoms accompanying the injury. In many cases, however, the treatment should be complex and include a variety of medical interventions and combination therapy.
Citation: Medicines
PubDate: 2024-04-30
DOI: 10.3390/medicines11050010
Issue No: Vol. 11, No. 5 (2024)
- Medicines, Vol. 11, Pages 11: Medicines—Aims and Scope Updates
Authors: Hiroshi Sakagami
First page: 11
Abstract: The journal Medicines (ISSN 2305-6320) was launched in 2014 [...]
Citation: Medicines
PubDate: 2024-05-14
DOI: 10.3390/medicines11050011
Issue No: Vol. 11, No. 5 (2024)
- Medicines, Vol. 11, Pages 8: Improved Outcomes in Eosinophilic Esophagitis
with Higher Medication Possession Ratio
Authors: Nathan T. Kolasinski, Eric A. Pasman, Cade M. Nylund, Patrick T. Reeves, Daniel I. Brooks, Katerina G. Lescouflair, Steve B. Min
First page: 8
Abstract: Eosinophilic esophagitis (EoE) disease activity can be caused by treatment non-adherence. Medication possession ratio (MPR) is an established metric of medication adherence. A higher MPR correlates with better outcomes in several chronic diseases, but MPR has not been investigated with respect to EoE. A retrospective cohort study was performed using an established EoE registry for the years 2005 to 2020. Treatment periods were identified, MPRs were calculated, and medical records were assessed for histologic remission (<15 eos/hpf), dysphagia, food impaction, stricture occurrence, and esophageal dilation that corresponded to each treatment period. In total, 275 treatment periods were included for analysis. The MPR in the histologic remission treatment period group was 0.91 (IQR 0.63–1) vs. 0.63 (IQR 0.31–0.95) for the non-remission treatment period group (p < 0.001). The optimal MPR cut-point for histologic remission was 0.7 (Sen 0.66, Spec 0.62, AUC 0.63). With MPRs ≥ 0.7, there were significantly increased odds of histologic remission (odds ratio 3.05, 95% confidence interval 1.79–5.30) and significantly decreased odds of dysphagia (OR 0.27, 95% CI 0.15–0.45), food impaction (OR 0.26, 95% CI 0.11–0.55), stricture occurrence (OR 0.52 95% CI 0.29–0.92), and esophageal dilation (OR 0.29, 95% CI 0.15–0.54). Assessing MPR before repeating an esophagogastroduodenoscopy may decrease unnecessary procedures in the clinical management of eosinophilic esophagitis.
Citation: Medicines
PubDate: 2024-03-26
DOI: 10.3390/medicines11040008
Issue No: Vol. 11, No. 4 (2024)
- Medicines, Vol. 11, Pages 9: Human Leucocyte Antigen Genetics in
Idiosyncratic Drug-Induced Liver Injury with Evidence Based on the Roussel
Uclaf Causality Assessment Method
Authors: Rolf Teschke, Gaby Danan
First page: 9
Abstract: The human leucocyte antigen (HLA) allele variability was studied in cohorts of patients with idiosyncratic drug-induced liver injury (iDILI). Some reports showed an association between HLA genetics and iDILI, proposing HLA alleles as a potential risk factor for the liver injury. However, the strength of such assumptions heavily depends on the quality of the iDILI diagnosis, calling for a thorough analysis. Using the PubMed database and Google Science, a total of 25 reports of case series or single cases were retrieved using the terms HLA genes and iDILI. It turned out that in 10/25 reports (40%), HLA genetics were determined in iDILI cases, for which no causality assessment method (CAM) was used or a non-validated tool was applied, meaning the findings were based on subjective opinion, providing disputable results and hence not scoring individual key elements. By contrast, in most iDILI reports (60%), the Roussel Uclaf Causality Assessment Method (RUCAM) was applied, which is the diagnostic algorithm preferred worldwide to assess causality in iDILI cases and represents a quantitative, objective tool that has been well validated by both internal and external DILI experts. The RUCAM provided evidence-based results concerning liver injury by 1 drug class (antituberculotics + antiretrovirals) and 19 different drugs, comprising 900 iDILI cases. Among the top-ranking drugs were amoxicillin–clavulanate (290 cases, HLA A*02:01 or HLA A*30:02), followed by flucloxacillin (255 cases, HLA B*57:01), trimethoprim–sulfamethoxazole (86 cases, HLA B*14:01 or HLA B*14:02), methimazole (40 cases, HLA C*03:02), carbamazepine (29 cases, HLA A*31:01), and nitrofurantoin (26 cases, HLA A*33:01). In conclusion, the HLA genetics in 900 idiosyncratic drug-induced liver injury cases with evidence based on the RUCAM are available for studying the mechanistic steps leading to the injury, including metabolic factors through cytochrome P450 isoforms and processes that activate the innate immune system to the adaptive immune system.
Citation: Medicines
PubDate: 2024-04-11
DOI: 10.3390/medicines11040009
Issue No: Vol. 11, No. 4 (2024)
- Medicines, Vol. 11, Pages 6: ADME Gene-Related Pharmacogenomic Labeling of
FDA-Approved Drugs: Comparison with Clinical Pharmacogenetics
Implementation Consortium (CPIC) Evidence Levels
Authors: Subrata Deb, Robert Hopefl, Anthony Allen Reeves, Dena Cvetkovic
First page: 6
Abstract: Pharmacogenomics (PGx) can facilitate the transition to patient-specific drug regimens and thus improve their efficacy and reduce toxicity. The aim of this study was to evaluate the overlap of PGx classification for drug absorption, distribution, metabolism, and elimination (ADME)-related genes in the U.S. Food and Drug Administration (FDA) PGx labeling and in the Clinical Pharmacogenetics Implementation Consortium (CPIC) database. FDA-approved drugs and PGx labeling for ADME genes were identified in the CPIC database. Drugs were filtered by their association with ADME (pharmacokinetics)-related genes, PGx FDA labeling class, and CPIC evidence level. FDA PGx labeling was classified as either actionable, informative, testing recommended, or testing required, and varying CPIC evidence levels as either A, B, C, or D. From a total of 442 ADME and non-ADME gene–drug pairs in the CPIC database, 273, 55, and 48 pairs were excluded for lack of FDA labeling, mixed CPIC evidence level provisional classification, and non-ADME gene–drug pairs, respectively. The 66 ADME gene–drug pairs were classified into the following categories: 10 (15%) informative, 49 (74%) actionable, 6 (9%) testing recommended, and 1 (2%) testing required. CYP2D6 was the most prevalent gene among the FDA PGx labeling. From the ADME gene–drug pairs with both FDA and CPIC PGx classification, the majority of the drugs were for depression, cancer, and pain medications. The ADME gene–drug pairs with FDA PGx labeling considerably overlap with CPIC classification; however, a large number of ADME gene–drug pairs have only CPIC evidence levels but not FDA classification. PGx actionable labeling was the most common classification, with CYP2D6 as the most prevalent ADME gene in the FDA PGx labeling. Health professionals can impact therapeutic outcomes via pharmacogenetic interventions by analyzing and reconciling the FDA labels and CPIC database.
Citation: Medicines
PubDate: 2024-02-20
DOI: 10.3390/medicines11030006
Issue No: Vol. 11, No. 3 (2024)
- Medicines, Vol. 11, Pages 7: Triple Silencing of HSP27, cFLIP, and CLU
Genes Promotes the Sensitivity of Doxazosin-Induced Apoptosis in PC-3
Prostate Cancer Cells
Authors: Jeong Man Cho, Sojung Sun, Eunji Im, Hyunwon Yang, Tag Keun Yoo
First page: 7
Abstract: Background: This study investigated how the expression of heat shock protein 27 (HSP27), cellular FLICE-like inhibitory protein (cFLIP), and clusterin (CLU) affects the progression of cancer cells and their susceptibility to doxazosin-induced apoptosis. By silencing each of these genes individually, their effect on prostate cancer cell viability after doxazosin treatment was investigated. Methods: PC-3 prostate cancer cells were cultured and then subjected to gene silencing using siRNA targeting HSP27, cFLIP, and CLU, either individually, in pairs, or all together. Cells were then treated with doxazosin at various concentrations and their viability was assessed by MTT assay. Results: The study found that silencing the CLU gene in PC-3 cells significantly reduced cell viability after treatment with 25 µM doxazosin. In addition, the dual silencing of cFLIP and CLU decreased cell viability at 10 µM doxazosin. Notably, silencing all three genes of HSP27, cFLIP, CLU was most effective and reduced cell viability even at a lower doxazosin concentration of 1 µM. Conclusions: Taken together, these findings suggest that the simultaneous silencing of HSP27, cFLIP, and CLU genes may be a potential strategy to promote apoptosis in prostate cancer cells, which could inform future research on treatments for malignant prostate cancer.
Citation: Medicines
PubDate: 2024-02-21
DOI: 10.3390/medicines11030007
Issue No: Vol. 11, No. 3 (2024)
- Medicines, Vol. 11, Pages 4: A Multi-Modality Intervention Improves
Obesity Bias among Medical Students
Authors: Stephanie Trofymenko, Randa Kutob, Amit Algotar
First page: 4
Abstract: Background: Obesity is linked to chronic diseases in adults and children. Its prevalence continues to grow in the United States, necessitating the need for healthcare provider training and presenting an opportunity for the education of future medical providers. Despite this need, effectively implementing obesity education into medical school curricula has been challenging. Anti-obesity bias amongst healthcare providers and trainees represents a significant obstacle to the care of patients with obesity. Obesity bias may affect up to 1/3 of medical students. Methods: This study describes the development and preliminary testing of a brief, 2.5 h multi-modality teaching intervention consisting of online, interactive, and independent learning modules for first-year medical students and a patient panel focused on obesity, obesity bias, and motivational interviewing. The participants took Crandall’s anti-fat attitude (AFA) questionnaire before and after an online independent learning module on motivational interviewing and obesity bias. The AFA consists of three subscales (“dislike”, “fear of fat”, and “willpower”). Individual responses were measured using a nine-point Likert-type response format (0 = very strongly disagree; 9 = very strongly agree). An average composite score was calculated for each subscale. Results: Data were analyzed from 103 first-year medical students enrolled at a college of medicine in the southwestern United States in 2022. The AFA mean composite scores decreased significantly, indicating a decrease in explicit anti-obesity attitude bias after completing the online module. This decrease was present in all three domains of fear (4.63 vs. 3.72, p < 0.001), dislike (1.25 vs. 0.88, p < 0.001) and willpower (3.23 vs. 2.31, p < 0.001). Conclusions: Relatively brief educational interventions can positively impact students’ anti-obesity attitudes.
Citation: Medicines
PubDate: 2024-01-28
DOI: 10.3390/medicines11020004
Issue No: Vol. 11, No. 2 (2024)
- Medicines, Vol. 11, Pages 5: Can a Low-Phosphate Diet for Chronic Kidney
Disease Treat Cancer' An Interdisciplinary Literature Review
Authors: Ronald B. Brown, Philip Bigelow
First page: 5
Abstract: Background: Cancer therapeutics have a low success rate in clinical trials. An interdisciplinary approach is needed to translate basic, clinical, and remote fields of research knowledge into novel cancer treatments. Recent research has identified high dietary phosphate intake as a risk factor associated with cancer incidence. A model of tumor dynamics predicted that reducing phosphate levels sequestered in the tumor microenvironment could substantially reduce tumor size. Coincidently, a low-phosphate diet is already in use to help patients with chronic kidney disease manage high serum phosphate levels. Methods: A grounded-theory literature-review method was used to synthesize interdisciplinary findings from the basic and clinical sciences, including oncology, nephrology, nutritional epidemiology, and dietetic research on cancer. Results: Findings of tumor remission associated with fasting and a ketogenic diet, which lower intake of dietary phosphate, support the hypothesis that a low-phosphate diet will reduce levels of phosphate sequestered in the tumor microenvironment and reduce tumor size. Additionally, long-term effects of a low-phosphate diet may reverse dysregulated phosphate metabolism associated with tumorigenesis and prevent cancer recurrence. Conclusions: Evidence in this article provides the rationale to test a low-phosphate diet as a dietary intervention to reduce tumor size and lower risk of cancer recurrence.
Citation: Medicines
PubDate: 2024-01-30
DOI: 10.3390/medicines11020005
Issue No: Vol. 11, No. 2 (2024)
- Medicines, Vol. 11, Pages 3: Dimeric 3,5-Bis(benzylidene)-4-piperidones:
Tumor-Selective Cytotoxicity and Structure-Activity Relationships
Authors: Swagatika Das, Praveen K. Roayapalley, Hiroshi Sakagami, Naoki Umemura, Dennis K. J. Gorecki, Mohammad Hossain, Masami Kawase, Umashankar Das, Jonathan R. Dimmock
First page: 3
Abstract: Background: The objective of this study is to find novel antineoplastic agents that display greater toxicity to malignant cells than to neoplasms. In addition, the mechanisms of action of representative compounds are sought. This report describes the cytotoxicity of a number of dimers of 3,5-bis(benzylidene)-4-piperidones against human malignant cells (promyelocytic leukemia HL-60 and squamous cell carcinoma HSC-2, HSC-3, and HSC-4). Methods: Tumor specificity was evaluated by the selectivity index (SI), that is the ratio of the mean CC50 for human non-malignant oral cells (gingival fibroblasts, pulp cells, periodontal ligament fibroblasts) to that for malignant cells. Results: The compounds were highly toxic to human malignant cells. On the other hand, these molecules were less toxic to human non-malignant cells. In particular, a potent lead molecule, 3b, was identified. A QSAR study revealed that the placement of electron-releasing and hydrophilic substituents into the aryl rings led to increases in cytotoxic potencies. The modes of action of a lead compound discovered in this study designated 3b were the activation of caspases-3 and -7, as well as causing PARP1 cleavage and G2 arrest, followed by sub-G1 accumulation in the cell cycle. This compound also depolarized the mitochondrial membrane and generated reactive oxygen species in human colon carcinoma HCT116 cells. In conclusion, this study has revealed that, in general, the compounds described in this report are tumor-selective cytotoxins.
Citation: Medicines
PubDate: 2024-01-11
DOI: 10.3390/medicines11010003
Issue No: Vol. 11, No. 1 (2024)
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