Current Reviews in Clinical and Experimental Pharmacology最新文献

Background: Sodium-glucose Co-transporter-2 Inhibitors (SGLT2is) are recommended for heart failure based on clinical outcomes. However, there is a lack of evidence linking SGLT2is with changes in cardiac function parameters.

Aim: This study aimed to systematically evaluate the literature assessing the impact of SGLT2is on various cardiac parameters.

Methods: Randomized clinical trials assessing any of the cardiac function parameters (atrial, valvular, pulmonary artery, and left ventricular) with SGLT2is were included. Mixed treatment comparison pooled estimates (mean differences (MD); 95% confidence intervals (95% CI)) were generated using a random-effects model and validated using trial sequential and bootstrap analyses. Intraclass differences and sub-group analysis in heart failure were evaluated.

Results: Thirty-four studies (2930 participants) were included in the review, of which 31 (2616 participants) were included in the meta-analysis. SGLT2is were associated with a significant increase in left ventricular ejection fraction (MD: 0.73; 95% CI: 0.09, 1.37%) and reductions in left ventricular mass (MD: -0.21; 95% CI: -0.39, -0.03 g), left ventricular mass index (MD: -0.22; 95% CI: - 0.36, -0.08 g/m2), left ventricular end-diastolic diameter (MD: -0.71; 95% CI: -1.29, -0.13 cm), left ventricular end-diastolic volume (MD: -0.56; 95% CI: -1.02, -0.1 ml), left atrial volume index (MD: -0.35; 95% CI: -0.58, -0.04 ml/m²), and pulmonary artery systolic pressure (MD: -1.08; 95% CI: - 1.94, -0.21 mmHg). Significant improvements in various cardiac parameters were observed in studies conducted on heart failure.

Conclusion: The findings of this study assessing cardiac function parameters support the guidelines recommending SGLT2 inhibitors in heart failure, which are primarily based on clinical outcomes.

Background: Despite the potential side effects of local anesthetics, they are indispensable for relieving pain and, consequently, reducing the patient's stress.

Objective: The objective of the present research was to evaluate, through a systematic review, the different types of local anesthetics available for use in dental procedures in pregnant patients.

Methods: Electronic bibliographic searches were conducted to retrieve studies published from 2000 to 2024 concerning the use of local anesthetics in pregnant women in dentistry. Five studies were included in this review (2 case series, 2 cohort studies, and 1 randomized clinical trial).

Results: The studies involved a total of 1,954 patients. The primary local anesthetic used was lidocaine with epinephrine/adrenaline. There were no significant differences in pregnant women who received local anesthesia regarding gestational age at delivery, birth weight of the baby, induction of labor pain, preterm birth delivery, spontaneous abortions, stillbirths, fetal anomalies, risk of experiencing serious medical adverse events or adverse pregnancy outcomes. A limited number of studies were identified, and the information was restricted.

Conclusion: Both the present review and previous studies support the lack of grounds to avoid providing dental care and using local anesthetics during pregnancy.

Background: Arrhythmia is an abnormal sinus rhythm of the heartbeat, and in addition to threatening the patient's health, it may also cause fatal complications.

Objectives: The present review study was investigated the effects of berberine (BBR) on cardiac arrhythmias and its possible complications.

Methods: A systematic search was conducted on electronic databases such as PubMed/MEDLINE, Web of Science, Scopus, Embase, and Cochrane Library to identify relevant studies published before June 10, 2024. Inclusion criteria were defined based on the study's aim. Two reviewers performed data extraction independently to ensure accuracy and minimize bias. The data were finally extracted and analyzed.

Results: Finally, 22 studies were included. BBR revealed antiarrhythmic effects through antioxidant, anti-inflammatory, and anti-apoptotic activity and improved mitochondrial function. Moreover, BBR modulated ion channels and improved electrical remodeling trough inhibited Potassium current (IK), IK1, IKr, IKs, ICa, INa, KATP channels and human ether-a-go-go related gene (hERG) and improved expression of inwardly rectifying potassium (Kir)6.2 and Kir2.1. It also increased action potential duration (APD), prolonged the effective refractory period (ERP), and reduced the frequency and complexity of ventricular premature complexes (VPC). However, it causes some cardiovascular side effects, including prolonged QT interval, bradycardia, and hypotensive effects. BBR may also lead to gastrointestinal complications, immunosuppressive effects, and interaction with concomitant drugs.

Conclusion: Although BBR's cardioprotective properties have satisfactory effects on cardiac arrhythmia, it causes prolonged QT interval, bradycardia, hypotension, and cardiotoxicity. However, more clinical studies are needed to obtain more reliable results.

Introduction: Experimental evidence has demonstrated that compounds of natural origin possess adjuvant anti-cancer properties, and their combination with anti-cancer drugs has the potential to reduce drug resistance in cancer treatment exhibiting chemoprotective effects.

Method: Fisetin (FIS), a flavonoid-structured polyphenolic compound found in various vegetables and fruits, is used as a yellow/ochre coloring agent and shows diverse pharmacological and biological effects. FIS can modulate various signaling pathways in relation to oxidative stress, inflammation, cell proliferation, metastasis, and angiogenesis. Thus, FIS is proposed to be a beneficial agent for preventing and treating numerous human malignancies. Awareness of natural compound action mechanisms paves the way for scientific communities, healthcare organizations, and the pharmaceutical industry to develop and introduce new drugs to treat diseases. In this paper, the general properties of FIS were highlighted first, and later, using the Scopus database, all related scientific literature regarding the studies that investigated the effects of FIS on lung cancer was collected.

Results: The critical points were extracted from the research works, and possible effects and molecular mechanisms of FIS on cancer cells were reviewed, and a comprehensive discussion about the roles of this phytochemical on different signaling pathways that were very crucial in lung cancer cells was provided.

Conclusion: Finally, the current challenges and future perspectives of lung cancer prevention and therapy approaches using FIS were addressed.

Introduction: Statin-induced myopathy (SIM) is a prevalent adverse event impacting treatment adherence. Despite extensive exploration of genotypes, conflicting evidence obscures their role in SIM incidence, prompting this network meta-analysis.

Methods: Observational studies meeting eligibility criteria (patients on any statin with reported SNPs and SIM details) were systematically reviewed. Severe SIM was defined as creatine kinase elevations exceeding 10 times the upper limit of normal. Mixed treatment comparison pooled estimates were generated from direct and indirect pooled estimates, represented by odds ratios (OR) with 95% confidence intervals (CI), and validated via bootstrap analysis.

Results: Thirty-four studies (26,152 participants) examining genotypes spanning drug transporters, metabolizing enzymes, reactive oxygen species production, and myopathy-related genes were analyzed. Significant associations were observed with drug transporters (OR: 1.4; 95% CI: 1.04, 1.5). Notably, solute carrier organic anion transporter 1B1 (SLCO1B1) (rs4149056) exhibited a moderate association with SIM (OR: 2.1; 95% CI: 1.7, 2.6), validated by bootstrap analysis (OR: 2.1; 95% CI: 1.7, 2.8). Similar associations were found for severe SIM with SLCO1B1 (rs4149056) (OR: 3.8; 95% CI: 1.4, 10.4) and ATP Binding Cassette Subfamily B Member 1 (ABCB1) (rs2373588) (OR: 2.8; 95% CI: 1.4, 5.4). Intraclass differences in genetic predictor risks were noted among statins.

Conclusion: Our meta-analysis underscores the significant association of SLCO1B1 with SIM, supporting its clinical utility. Further research is warranted to clarify additional genetic predictors. These findings endorse current guidelines advocating for SLCO1B1 genotyping in statin therapy decisions.

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.

Background: Bigles are novel formulation merging two phase of hydrogel and organogel revealing dual properties to release active agents based on their lipophilic or hydrophilic nature.

Methods: A systematic search was conducted in PubMed, Scopus, and ISI Web of Science to find eligible studies evaluating the efficiency of bigels in drug release. 20 articles were included in the analysis based on the defined criteria.

Results: The results indicated that several different natural materials were used for bigel making. Span (52.38%) and Sunflower oil (23.80%) were the most solvents used for organogel formation. Also, gelatin, agar, gums, and other types of biopolymer were used as hydroglators. Most research (33.33%) focused on the release of metronidazole from bigel structure. Also, the range of drug release rates was 1.59 - 100% and in 42.85% of studies was >90%. The nature, content, and properties of both organogel and hydrogel and some process variables such as temperature, mixing speed and storage conditions were highlighted as the main influential factors on bigel formation and its bioactivity.

Conclusion: Bigels are an innovative structure that provides desired physicochemical and rheological properties for industrial applications. Excellent biocompatibility and in vitro / ex vivo results have been documented for developed bigels. In this regard, an optimal preparation method is very important to show superior therapeutic effects.

Depression, a pervasive and disabling mental health disorder, presents a global healthcare challenge. Despite persistent research on its etiology and pathophysiology, many aspects remain unclear. Predominant neurobiological research and traditional pharmacotherapies have pointed out the monoamine hypothesis as a pivotal factor in the pathophysiology of depression. However, emerging perspectives on the monoamine hypothesis highlight the significance of the cholinergic system, a major regulator of diverse CNS functions encompassing attention, arousal, cognition, and memory. Cognitive impairments were frequently observed in depression along with other symptoms i.e. low mood and anhedonia. A comprehensive literature search was conducted across multiple databases (PubMed, Scopus, and Web of Science) from their inception until May 2023. We screened 1,200 articles, of which 400 full-text articles were assessed for eligibility, and 231 studies met the inclusion criteria. The review included both pre-clinical and clinical studies focusing on the role of acetylcholine (ACh) and its receptors in depression. Data extraction and quality assessment were performed independently by two reviewers. In literature, both pre-clinical and clinical studies suggest that elevated central ACh levels may contribute to depression, prompting investigations into intervention strategies targeting mAChRs/nAChRs and AChE. These receptors have become a critical target in drug-design strategies aimed at addressing depression-like symptoms. In addition, research has demonstrated a significant antidepressant-like effect of AChEIs in a dose-dependent manner in animal models. Hence, this evidence over the past decades underscores the pivotal role of the cholinergic system in mood regulation, offering promise for novel depression treatments. In this review, we tried to summarize the historical evolution of the cholinergic system from early discoveries to its role in the pathophysiology of depression. It presents evidence for the involvement of mAChRs and nAChRs, as well as AChE, in depression. By outlining the cholinergic theory of depression, this review suggests a novel therapeutic approach, emphasizing the role of ACh in the complex depression pathophysiology, and presenting avenues for further research and the development of targeted interventions.