{"title":"Beyond the Needle: Innovative Microneedle-Based Transdermal Vaccination.","authors":"Hiep X Nguyen","doi":"10.3390/medicines12010004","DOIUrl":"10.3390/medicines12010004","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicholas Pavlatos, Pawan Daga, Aangi Shah, Muhammad Khan, Jishanth Mattumpuram
{"title":"Thrombosed Mechanical Aortic Valve Treated with Low-Dose Ultraslow Alteplase Infusion.","authors":"Nicholas Pavlatos, Pawan Daga, Aangi Shah, Muhammad Khan, Jishanth Mattumpuram","doi":"10.3390/medicines12010003","DOIUrl":"10.3390/medicines12010003","url":null,"abstract":"<p><p><b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: She was found to have a subtherapeutic international normalized ratio and thrombosed mechanical aortic valve seen on transthoracic echocardiography, transesophageal echocardiography, and fluoroscopy. <b>Conclusions:</b> 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.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"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","doi":"10.3390/medicines12010002","DOIUrl":"10.3390/medicines12010002","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methodology: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ayda Awaness, Rania Elkeeb, Sepehr Afshari, Eman Atef
{"title":"The Pharmacokinetic Changes in Cystic Fibrosis Patients Population: Narrative Review.","authors":"Ayda Awaness, Rania Elkeeb, Sepehr Afshari, Eman Atef","doi":"10.3390/medicines12010001","DOIUrl":"10.3390/medicines12010001","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RETRACTED: Zulfiqar et al. Obesity and Frailty Syndrome in the Elderly: Prospective Study in Primary Care. <i>Medicines</i> 2022, <i>9</i>, 38.","authors":"Abrar-Ahmad Zulfiqar, Perla Habchi, Ibrahima Amadou Dembele","doi":"10.3390/medicines11080022","DOIUrl":"10.3390/medicines11080022","url":null,"abstract":"<p><p>The journal retracts the article titled \"Obesity and Frailty Syndrome in the Elderly: Prospective Study in Primary Care\" [...].</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"11 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11676820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Utility of Aprepitant in the Management of Pediatric Patients with Cyclical Vomiting Syndrome.","authors":"Aravind Thavamani, Sindhoosha Malay, Jasmine Khatana, Sujithra Velayuthan, Senthilkumar Sankararaman","doi":"10.3390/medicines11080021","DOIUrl":"10.3390/medicines11080021","url":null,"abstract":"<p><p><b>Introduction</b>: 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. <b>Methodology</b>: 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. <b>Results</b>: 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%, <i>p</i> = 0.91) readmission rate and results were not altered by propensity score matching. <b>Conclusions</b>: 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.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"11 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11677684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vítor Silva, Ricardo Madeira, João Joaquim, Cristiano Matos
{"title":"Safety Implications of Off-Label Medication Use in Athletes: A Narrative Review.","authors":"Vítor Silva, Ricardo Madeira, João Joaquim, Cristiano Matos","doi":"10.3390/medicines11080020","DOIUrl":"10.3390/medicines11080020","url":null,"abstract":"<p><p>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<sup>®</sup> (Medline), Scopus<sup>®</sup>, and Web of Science<sup>®</sup> 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.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"11 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Subhas S Karki, Umashankar Das, Jan Balzarini, Erik De Clercq, Hiroshi Sakagami, Yoshihiro Uesawa, Praveen K Roayapalley, Jonathan R Dimmock
{"title":"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","doi":"10.3390/medicines11080019","DOIUrl":"10.3390/medicines11080019","url":null,"abstract":"<p><p><b>Background:</b> A series of 3,5-benzylidene-4-piperidones, <b>1a</b>-<b>n</b>, 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. <b>Methods:</b> The bioevaluation of <b>1a</b>-<b>n</b> was undertaken using human Molt/4C8 and CEM cells as well as murine L1210 cells. Correlations were sought between the interplanar angles θ<sub>A</sub> and θ<sub>B</sub> 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, <b>1a</b>-<b>n</b> were evaluated against HSC-2, HSC-3, HSC-4 and HL60 neoplasms as well as non-malignant HGF, HPC and HPLF cells. <b>Results:</b> A positive correlation was noted between the interplanar angle θ<sub>A</sub> of one of the aryl rings and the adjacent olefinic linkage with IC<sub>50</sub> 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 IC<sub>50</sub> values of the compounds towards the Molt4/C8 and CEM cells. The dienones in series <b>1</b> demonstrated higher tumor-selective toxicity towards HSC-2, HSC-3, HSC-4 and HL-60 neoplasms than HGF, HPC and HPLF cells. <b>Conclusions:</b> The bioevaluations revealed some support for greater cytotoxic potencies to be displayed by compounds having ortho-substituents.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"11 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jovan Javorac, Dejan Živanović, Biljana Zvezdin, Vesna Mijatović Jovin
{"title":"Breathing for Two: Asthma Management, Treatment, and Safety of Pharmacological Therapy during Pregnancy.","authors":"Jovan Javorac, Dejan Živanović, Biljana Zvezdin, Vesna Mijatović Jovin","doi":"10.3390/medicines11070018","DOIUrl":"10.3390/medicines11070018","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"11 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jamie Thygerson, Dallin Oyler, Jackson Thomas, Brandon Muse, Benjamin D Brooks, Jessica E Pullan
{"title":"GDF15 Targeting for Treatment of Hyperemesis Gravidarum.","authors":"Jamie Thygerson, Dallin Oyler, Jackson Thomas, Brandon Muse, Benjamin D Brooks, Jessica E Pullan","doi":"10.3390/medicines11070017","DOIUrl":"10.3390/medicines11070017","url":null,"abstract":"<p><p>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-<i>β</i> 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.</p>","PeriodicalId":74162,"journal":{"name":"Medicines (Basel, Switzerland)","volume":"11 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}