Journal of Basic and Clinical Physiology and Pharmacology最新文献

Mirikizumab is a monoclonal antibody that targets the human IL-23p19 and has been humanized with IgG4. It is currently under development for treating Crohn's disease and ulcerative colitis. The FDA approved mirikizumab on October 26, 2023 as a highly effective treatment for ulcerative colitis, providing patients with a new option for this chronic and debilitating inflammatory bowel disease. Millions of people worldwide suffer from ulcerative colitis, and it is crucial to induce and maintain remission. However, existing therapies may not suffice in terms of efficacy or patient tolerability. Mirikizumab demonstrated a favorable safety profile during trials, with reported adverse events aligning with anticipated outcomes in the patient group. These safety results underscore the viability of mirikizumab as a well-tolerated therapeutic option for extended use. The trials data indicated that the treatment not only swiftly alleviated symptoms but also exhibited potential for sustaining remission over an extended period. This article seeks to offer a condensed overview of the noteworthy clinical trial outcomes that contributed to the development of mirikizumab, ultimately leading to its initial approval for the treatment of ulcerative colitis.

This review explores the interplay between type 2 diabetes mellitus (T2DM) and urinary microbiome dysbiosis, focusing on its role in urinary tract infections (UTIs). Once considered sterile, the urinary tract hosts a diverse microbiota that supports mucosal immunity and pathogen resistance. In T2DM, chronic hyperglycemia and glycosuria disrupt microbial balance, impair immune responses, and increase UTI susceptibility. Glycosuria promotes pathogenic colonization, biofilm formation, and microbial shifts, with studies reporting a threefold rise in Escherichia coli and a 56 % reduction in Lactobacillus spp. in diabetic women with recurrent UTIs. Diabetic urine shows reduced diversity, higher abundance of Klebsiella, Pseudomonas, and Enterococcus, and elevated IL-8. Microbiota-targeted interventions, including probiotics (Lactobacillus crispatus, Lactobacillus rhamnosus GR-1), prebiotics (astaxanthin), and phytotherapeutics (cranberry), demonstrate potential via lactic acid, hydrogen peroxide production, competitive exclusion, and NF-κB modulation. A 12-month RCT showed significant UTI recurrence reduction with probiotics. Advances in 16 S rRNA sequencing and metagenomics reveal microbial signatures associated with diabetic UTIs, though methodological heterogeneity limits comparability. A review of 1,200 publications (2000-2024) highlights the need for longitudinal studies and precision microbiota therapeutics to translate findings into clinical practice.

Sarcopenia and malnutrition are increasingly recognized as major determinants of morbidity and functional decline in aging and chronically ill populations. Thyroid hormones (THs), particularly triiodothyronine (T3), play a critical role in regulating skeletal muscle homeostasis, influencing myogenesis, mitochondrial function, metabolic rate, and fibre-type specification. Alterations in thyroid function, both hypo- and hyperthyroidism, negatively impact muscle protein turnover, leading to impaired strength and muscle wasting. Notably, nutritional status modulates TH metabolism at multiple levels: malnutrition impairs deiodinase activity, alters TH transport, and reduces peripheral T3 availability, thereby contributing to the low T3 syndrome frequently observed in frail or undernourished individuals. Conversely, excessive T3 levels, as seen in hyperthyroid states or during inappropriate replacement therapy, exacerbate catabolism and accelerate muscle loss. This review synthesizes current evidence on the bidirectional interactions among thyroid dysfunction, nutritional deficiencies, and sarcopenia, proposing an integrative pathophysiological model. We discuss the clinical implications of TH replacement in sarcopenic and malnourished patients, highlighting the need for personalised, multimodal interventions that include hormonal, nutritional, and physical strategies to prevent or mitigate muscle deterioration in endocrine and geriatric contexts.

Objectives: To define the pattern of symptoms and severity of GERD among premenopausal and postmenopausal women in relation to estrogen levels and endoscopy findings.

Methods: The research was carried out in the Laboratory of Gastrointestinal Motility inside the Gastroenterology Department at PSGIMS&R, Coimbatore and the following approval from Institutional Human Ethics Committee (IHEC).

Results: The findings reveal significant variations in estrogen levels between premenopausal and postmenopausal women with gastroesophageal reflux disease (GERD), with premenopausal women having higher levels (82.80 ± 27.91 to 150.43 ± 40.80 pg/mL) compared to postmenopausal women (6.05 ± 2.75 to 17.30 ± 5.43 pg/mL, p < 0.001). This decline in estrogen post-menopause is associated with increased GERD symptoms and endoscopic abnormalities.

Conclusion: The study concludes that reduced estrogen levels in postmenopausal women are linked to a higher prevalence of GERD symptoms, including heartburn and dysphagia, compared to premenopausal women. Endoscopic findings further support the correlation between hormonal changes and GERD severity, highlighting the necessity for careful evaluation of GERD risk factors.

Objectives: To assess the relationship between adiponectin levels, nutritional indices, and sarcopenia in elderly diabetic patients, and to identify metabolic and nutritional biomarkers that distinguish sarcopenic from non-sarcopenic elderly diabetic individuals.

Methods: This cross-sectional study included 80 diabetic patients aged >60 years, sarcopenic (n=40) and non-sarcopenic (n=40) groups based on Asian Working Group for Sarcopenia criteria. Serum adiponectin, glucose metabolism markers, lipid profiles, and nutritional indices including prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and controlling nutritional status (CONUT) score were assessed.

Results: Sarcopenic patients demonstrated significantly higher adiponectin levels (12.8 ± 3.4 vs. 8.4 ± 2.1 μg/mL, p<0.001), representing a 52% increase compared to non-sarcopenic individuals. The sarcopenic group showed impaired insulin sensitivity (QUICKI: 0.31 ± 0.05 vs. 0.36 ± 0.04, p=0.003), elevated atherogenic indices, and reduced nutritional status. All nutritional indices were significantly impaired in the sarcopenic group: PNI (45.2 ± 5.4 vs. 52.4 ± 6.8, p<0.001), GNRI, and CONUT score. Multiple logistic regression identified adiponectin (OR=1.264, 95% CI: 1.062-1.504, p=0.009), age, insulin resistance, and nutritional indices as independent predictors of sarcopenia.

Conclusions: Elevated adiponectin levels paradoxically associate with sarcopenia in elderly diabetes, suggesting a potential biomarker for muscle wasting. The association between nutritional indices and sarcopenia emphasizes the importance of comprehensive nutritional assessment in elderly diabetic patients.

Objectives: Myasthenia gravis (MG) is a chronic autoimmune disease primarily affecting skeletal muscles, though cardiac involvement, particularly arrhythmias, may occur, especially in severe cases or in patients with thymoma.

Case presentation: We report the case of a 62-year-old male with AchR-Ab-positive MG, without thymoma, who developed an advanced atrioventricular block requiring pacemaker implantation. Cardiac manifestations in MG can result from either the disease itself - through myocarditis, autoantibodies and autonomic dysfunction - or as a side effect of treatments such as pyridostigmine and immunosuppressants. Management strategies include considering discontinuation of pyridostigmine or using hyoscyamine to assess potential drug-induced bradyarrhythmias before proceeding with permanent pacing.

Conclusions: This case highlights the diagnostic challenges in distinguishing iatrogenic from autoimmune cardiac complications and emphasizes the importance of cardiovascular monitoring in MG patients, especially those presenting with cardiac symptoms or EKG abnormalities. Early recognition and appropriate intervention are crucial to improve outcomes and quality of life.

Background: Mental toughness represents a crucial psychological construct in competitive sports. This narrative review examines the relationship between mental toughness and athletic performance across various sports domains.

Methods: We conducted a comprehensive literature review of empirical studies published between 2000 and 2024. Relevant articles were identified through database searches including PubMed, PsycINFO, SPORTDiscus, and Web of Science. Studies examining mental toughness in relation to performance outcomes in competitive athletes were included.

Results: Evidence consistently shows positive correlations between mental toughness and athletic performance (r=0.21-0.63). Mental toughness demonstrates stronger associations with performance in individual sports compared to team sports. Additionally, psychological interventions targeting mental toughness components show promise for enhancing athletic outcomes.

Conclusions: Mental toughness represents a significant psychological factor in athletic achievement. The construct influences performance through multiple pathways including resilience to pressure, emotional regulation, and focus maintenance. Practical applications for coaches and sport psychologists are discussed.

Objectives: The current study aims to evaluate the aptness of prescription in elderly along with looking out for polypharmacy, overprescribing and under prescribing in geriatric patients being treated at the tertiary care hospital.

Methods: This is a retrospective record-based study, data was collected from 1st January 2017 to 31st December 2018 of all the patient which are falling in the inclusion criteria. Prescription appropriateness was assessed implementing 'Beers criteria'. Errors in prescription along with administration were checked by direct observation and analysis of prescriptions.

Results: Out of total 2,718 patients, 58.6 % were found to be males and 41.4 % were females. Most common comorbidities found were hypertension and coronary artery diseases (CAD). In the current study, 39 % of the prescription contained inappropriate medication and 11.20 % prescriptions were having adverse drug reaction. Error by attending nurse in prescription reading came out to be the most common error in this study.

Conclusions: Diclofenac was found to be the most commonly used inappropriate drug as per Beer's criteria. Clinicians should be more cautious when using drugs in old age patients.

Objectives: This study aims to assess the prevalence, characteristics, and risk factors of potential QT-prolonging drug-drug interactions (pQT-DDIs) in cancer patients, including identifying drug combinations contributing to QT prolongation and key predictors.

Methods: In this hospital-based, cross-sectional observational study, all types of cancer patients, irrespective of age or sex, were included over 1 year. pQT-DDIs were identified using four drug interaction checker software tools. Predictors were analyzed using univariate logistic regression.

Results: A total of 1,331 cancer patients were included. The prevalence of pQT-DDIs was 67.6 %. Of these, 606 (45.5 %) had 1-2 pQT-DDIs, 126 (9.5 %) had 3-4, and 78 (5.9 %) had 5-6. Overall, 163 drug combinations were identified as causing QT prolongation; 122 were detected by Drugs.com. Significant predictors included >8 drugs prescribed (OR=6.46; CI=4.87-8.56; p<0.0001), >2 anticancer drugs (OR=1.68; CI=1.14-2.46; p=0.008), >6 adjuvant drugs (OR=6.83; CI=5.17-9.03; p<0.0001), solid cancers (OR=6.59; CI=4.59-8.80; p<0.0001), and cytotoxic drug use (OR=2.40; CI=1.52-3.77; p=0.0001).

Conclusions: There is a high prevalence of pQT-DDIs in cancer patients. Those receiving multiple anticancer and adjuvant drugs are at higher risk. Routine interaction screening is recommended before chemotherapy.

Primary biliary cholangitis (PBC) is a chronic liver disease leading to liver damage and potentially death. The first-line treatment is ursodeoxycholic acid (UDCA), but some patients do not respond well. Obeticholic acid (OCA) is a second-line treatment option. Fenofibrate (a predominantly PPAR-α agonist) and bezafibrate (a pan-PPAR agonist) are currently used in clinical practice as anticholestatic agents to improve serum biochemistry in PBC. Seladelpar, a peroxisome proliferator-activated receptor-delta (PPARδ) agonist, has demonstrated potent anti-cholestatic effects in clinical studies. The aim of this analysis was to summarise the data available on efficacy and safety of seladelpar for the treatment of primary biliary cholangitis (PBC). We conducted a search in PubMed, Embase and Web of Science for studies on seladelpar until June 1, 2024. The analysis included review articles, randomized controlled trials, cohort studies and case-control studies. Seladelpar is a once daily oral, potent and selective PPAR-δ agonist. Activation of PPAR-δ on hepatocytes and cholangiocytes improves cholestasis by downregulating the rate-limiting enzyme, CYP 7A1, used for bile synthesis, as well as reducing cholesterol synthesis and dietary absorption, leading to a reduction in bile acid pools. In this review, we have summarised the preclinical and clinical data on seladelpar. There is a need for additional phase III studies to provide sufficient clinical evidence for the efficacy and safety of this investigational drug, as current evidence is limited to phase III studies and does not yet prove its worth in a larger population.