Current Reviews in Clinical and Experimental Pharmacology最新文献

Ketamine, a substance used for anesthesia and known for inducing dissociation, can lead to addiction and the development of severe withdrawal symptoms. Ketamine alters brain networks before affecting somesthetic sensation. Ketamine abuse was especially prevalent in East and Southeast Asia, and its popularity has continued to expand globally in recent decades. Ketamine is gaining popularity in the public and private sectors as a cheaper off-label depression treatment. Unfortunately, ketamine may cause side effects, such as heart and blood vessel instability, respiratory depression, liver injury, hallucinations, etc. The pain-relieving and mental effects of ketamine might induce reliance; thus, it should be used cautiously. This review highlights the neurobiological processes underpinnings of ketamine's addictive potential, withdrawal, and its effects on brain networks like the prefrontal cortex, hippocampus, and mesolimbic pathway, which play vital roles in decision-making, memory, and reward processing. In addition, the involvement of neurotransmitter systems, specifically glutamate and dopamine, in mediating the addictive properties of ketamine and the neuroadaptive changes that occurred during withdrawal are also discussed. It also explains that low-dose ketamine can alter the secretion of stress hormone cortisol and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, possibly attributed to the current repurposing study of ketamine as a fast-acting antidepressant. Understanding these pathways is essential for developing effective ketamine addiction treatments, managing withdrawal symptoms, and possibly reversing brain changes for the betterment of human health and psychological well- being.

Depression is a prevalent mood disorder with significant public health implications. Despite extensive research, its precise causes remain inadequately understood. Recently, interest has surged in the role of the gut microbiome and its metabolites in the pathophysiology of depression. This review aims to provide a comprehensive overview of the relationship between gut microbiota, its metabolites, and depression while exploring potential mechanisms influencing the efficacy of antidepressant medications. A narrative review methodology was employed, synthesizing recent studies utilizing a multi-omics approach. We examined alterations in gut microbiome composition and metabolite production in individuals diagnosed with depression, discussing the technical tools and methods commonly applied in this research area. The findings indicate that individuals with depression show significant alterations in gut microbiome composition, notably an imbalance in Firmicutes, Bacteroidetes, and Actinobacteria. Changes in metabolite production, including short-chain fatty acids, tryptophan, and bile acids, were also observed. Moreover, the review highlights that antidepressant medications may exert their therapeutic effects by modulating gut microbiota and its metabolites. This review emphasizes the intricate interplay between gut microbiota, its metabolites, and depression, revealing critical insights into the mechanisms underlying antidepressant efficacy. We recommend that future research focus on elucidating these interactions to develop innovative therapeutic strategies, potentially transforming the management of depression through microbiota-targeted approaches.

Examining antifungal resistance in dermatophytes is crucial in infectious diseases, dermatology, and clinical microbiology. The increasing occurrence of resistant infections and their influence on the effectiveness of therapy seem overwhelming. This study examines the present condition of antifungal resistance in dermatophytes, highlighting the need for ongoing and up-to-date research. Fungal diseases constantly change, and fungi have developed new resistance mechanisms. Here, we analyze the historical context of research on antifungal resistance, examining the variables that contribute to the development of resistance, such as the growing use of antifungals in clinical and agricultural contexts. We also explore the consequences of resistance to antifungal agents in clinical practice and public health. The review emphasizes the significance of new diagnostic technologies, like next-generation sequencing, in comprehending resistance mechanisms. It also underscores the crucial role of international collaboration in tackling this worldwide health concern. In conclusion, the paper emphasizes the need for continuous research to adjust to the evolving epidemiology of dermatophyte infections, create efficient treatment approaches, and guide public health interventions. This will ensure that the management of antifungal resistance is grounded in the most up-to-date scientific knowledge and optimal methods.

Natural products have historically driven pharmaceutical discovery, but their reliance has diminished with synthetic drugs. Approximately 35% of medicines originate from natural products. Scopoletin, a natural coumarin compound found in herbs, exhibits antioxidant, hepatoprotective, antiviral, and antimicrobial properties through diverse intracellular signaling mechanisms. Furthermore, it also enhances the activity of antioxidants. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes viral pneumonia through cytokine storms and systemic inflammation. Cellular autophagy pathways play a role in coronavirus replication and inflammation. The Silent Information Regulator 1 (SIRT1) pathway, linked to autophagy, protects cells via FOXO3, inhibits apoptosis, and modulates SIRT1 in type-II epithelial cells. SIRT1 activation by adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) enhances the autophagy cascade. This pathway holds therapeutic potential for alveolar and pulmonary diseases and is crucial in lung inflammation. Angiotensin-converting enzyme 2 (ACE-2) activation, inhibited by reduced expression, prevents COVID-19 virus entry into type-II epithelial cells. The coronavirus disease 2019 (COVID-19) virus binds ACE-2 to enter into the host cells, and XBB.1.5 COVID-19 displays high ACE-2-binding affinity. ACE-2 expression in pneumocytes is regulated by signal transducers and activators of transcription-3 (STAT3), which can increase COVID-19 virus replication. SIRT1 regulates STAT3, and the SIRT1/STAT3 pathway is involved in lung diseases. Therapeutic regulation of SIRT1 protects the lungs from inflammation caused by viral-mediated oxidative stress. Scopoletin, as a modulator of the SIRT1 cascade, can regulate autophagy and inhibit the entry and life cycle of XBB.1.5 COVID-19 in host cells.

Current therapeutic approaches for Huntington's disease (HD) focus on symptomatic treatment. Therefore, the unavailability of efficient disease-modifying medicines is a significant challenge. Regarding the molecular etiology, targeting the mutant gene or advanced translational steps could be considered promising strategies. The evidence in gene therapy suggests various molecular techniques, including knocking down mHTT expression using antisense oligonucleotides and small interfering RNAs and gene editing with zinc finger proteins and CRISPR-Cas9-based techniques. Several post-transcriptional and post-translational modifications have also been proposed. However, the efficacy and long-term side effects of these modalities have yet to be verified. Currently, cell therapy can be employed in combination with conventional treatment and could be used for HD in which the structural and functional restoration of degenerated neurons can occur. Several animal models have been established recently to develop cell-based therapies using renewable cell sources such as embryonic stem cells, induced pluripotent stem cells, mesenchymal stromal cells, and neural stem cells. These models face numerous challenges in translation into clinics. Nevertheless, investigations in Advanced Therapy Medicinal Products (ATMPs) open a promising window for HD research and their clinical application. In this study, the ATMPs entry pathway in HD management was highlighted, and their advantages and disadvantages were discussed.

Objective: There is a lack of evidence on the effectiveness of antidotes in the management of organophosphate and carbamate (OPC) poisoning. We aimed to review the efficacy and safety of glycopyrrolate in the management of OPC poisoning.

Methodology: Databases such as PubMed, Scopus, Embase, and Cochrane Library were extensively searched from inception to November 2022 and updated till October 2023. Interventional, observational, and descriptive studies assessing the efficacy and safety of glycopyrrolate administered in any dose, route, and duration for the management of OPC poisoning published in the English language were considered for this review. The treatment with any other regimen that did not include glycopyrrolate was regarded as the comparator. The survival, intensive care unit (ICU) and ventilatory outcomes were considered efficacy outcomes, and adverse effects were considered safety outcomes. Suitable quality assessment tools were used to assess the risk of bias in the included studies. Two independent reviewers were involved in the study selection, data extraction, and quality assessment and any discrepancies were resolved through mutual discussion or consultation with a third reviewer.

Results: A total of 9 studies (2 RCTs, 4 cohorts, 1 case series, and 2 case reports) out of 591 nonduplicate records were considered for this review. Overall, the RCTs were observed to have a moderate quality, and observational studies and descriptive studies were found to have good quality. All the included studies used atropine administration as a standard treatment option along with glycopyrrolate. The OPC patients treated with glycopyrrolate had a fewer hospitalization days with comparable recovery and ventilatory outcomes than those that had not been treated with glycopyrrolate. The occurrence of adverse events and complications was lower in the glycopyrrolate group than in the control group.

Conclusion: Currently, there is a lack of comparative studies to recommend the use of glycopyrrolate in OPC poisoning, and further interventional studies are required to make an evidencebased recommendation on this topic.

Botulinum toxin injections, a popular aesthetic treatment, have over 7.4 million beneficiaries in the U.S. Despite their safety record, these injections pose potential complications. It is essential for aesthetic practitioners to manage these complications with the least impact on the patient. Upper eyelid ptosis, though rare, is a significant side effect of botulinum toxin injections. Through our study, we have identified the etiology, anatomy, and therapeutic management of botulinum- induced blepharoptosis. Hence, the goal of this study was to identify the basic aetiology of blepharoptosis and manage this complication, as well as discuss the basis of medico-legal implications involving this popular drug. The complex medico-legal implications of botulinum toxin-induced blepharoptosis call for continuous discourse, education, and clarity on drug-use legal standards. With evolving global and Italian legislation, practitioners must ensure they meet care standards, weighing treatment benefits against potential legal and ethical outcomes. Blepharoptosis is a rare but significant complication of botulinum-type injections. Etiology and thorough anatomy are crucial for avoiding this complication and handling it with the least impact on the patient. Medico-legal implications are currently not fully established, but the basis of aesthetic treatment standards, as well as continuing medical education, will ensure correct medico-legal coverage of such complications.

Pulmonary hypertension (PH) is a severe, progressive disorder characterized by elevated pulmonary arterial pressure, leading to right ventricular failure and increased mortality. Despite advancements in management, the median survival for PH patients remains 5-7 years, with an inhospital mortality rate of approximately 6%. The core pathological feature of PH is pulmonary vascular remodeling (PVR), a multifactorial process involving endothelial dysfunction, inflammation, and aberrant immune responses. While current therapies target endothelial dysfunction, they fall short of preventing PVR or halting disease progression. Emerging research highlights the potential of immune-inflammatory pathways, oxygen-sensing mechanisms, and gut microbiota modulation as therapeutic targets. Integrating nutritional strategies, probiotics, and fecal microbiota transplantation (FMT) as adjunctive therapies also shows promise. These factors may collectively influence PVR, offering novel insights into therapeutic avenues for PH management in the future.

Previous genetic studies on the genetic makeup of Arab populations highlight the diversity resulting from the distribution of specific genetic markers among various Arab descendant populations. Different genetic variants classified as clinically significant have been identified, impacting the response to administered drugs. Absorption, distribution, and excretion of drugs throughout the human body are managed through the actions of drug transporters and receptor proteins, which are expressed on the cellular membrane. Drug metabolism involves activating or inactivating various compounds, transforming them into therapeutically active or toxic metabolites. With the rapid advancement of pharmacogenetic testing techniques and increased genetic studies involving Arab populations, insights into genetic polymorphisms have emerged, leading to a better understanding of the diverse phenotypes of drug response associated with genotype variation. Variations in transporters and receptor genes have significantly contributed to generating variant phenotypes that affect individuals' responses to treatments and substrates. This necessitates administering individualized drug doses based on the patient's haplotype, which can be determined through advanced genetic diagnosis. This review summarizes the findings of recent pharmacogenetic studies in the Arab world, emphasizing the benefits of pharmacogenetic research and applications to enhance therapeutic aspects of healthcare and treatment among patients in Arab countries.