Rashid Latif Medical College

Parkinson’s disease (PD) is second most common neurodegenerative disorder characterized by gradual loss of dopaminergic neurons in the substantia nigra. Its pathophysiology reflects interlinked processes of oxidative stress, inflammation, and altered gene expressions of ubiquitin-proteasome pathway. The current therapy, L-DOPA (Sinemet) provides only symptomatic relief without modifying disease progression. This study aimed to evaluate stigmasterol, a bioactive phytocompound having antioxidant and anti-inflammatory properties and blood brain barrier permeability, as a potential candidate for modifying disease progression in PD. PD was induced in mice using neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Animals were randomly assigned to five groups: healthy control (HC), MPTP only (PC), MPTP + Sinemet (SC), MPTP + stigmasterol therapeutic (StigTx), and stigmasterol preventive (StigPre). Oxidative stress markers, inflammatory mediators (IL-1β, IL-6, TNF-α, CRP), hepatic and renal markers were evaluated. Dopaminergic neuronal survival was examined by tyrosine hydroxylase immunostaining, and PD-related gene expression (PRKN, PINK1, UCHL1, LRRK2) was analysed. MPTP exposure caused marked motor decline, strong oxidative stress and inflammation. Sinemet partially improved motor functions and antioxidant status but showed limited effects on lipid peroxidation and induced mild hepatic stress. In contrast, stigmasterol reduced inflammation, enhanced antioxidant defences, and improved motor ability without inducing organ toxicity. Preventive use showed more promising results by preserving dopaminergic neurons and modulated PD related gene expression. Stigmasterol improves motor dysfunction and provides significant neuroprotection, highlighting its potential as a multitarget therapeutic candidate capable of modifying disease related molecular pathways.

OBJECTIVE:Propofol is widely used for gastrointestinal (GI) endoscopies but may cause respiratory depression and hemodynamic compromise when used alone. Adjuncts such as ketamine or esketamine and fentanyl-class opioids (fentanyl, alfentanil, and sufentanil) are used to optimize sedation, yet their comparative efficacy and safety remain uncertain. This meta-analysis evaluated ketamine or esketamine plus propofol (KP regimens) versus fentanyl/alfentanil/sufentanil plus propofol (FP regimens). METHODS:Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed, Scopus, Cochrane Library, and Google Scholar from inception to February 2025 for randomized controlled trials (RCTs). Eligible studies included patients undergoing GI endoscopy (Population), receiving ketamine or esketamine with propofol (Intervention), compared with fentanyl-class opioids with propofol (Comparison), and reporting outcomes including propofol dose, comfort, adverse events, recovery time, or procedure time (Outcomes). Risk of bias was assessed with the Cochrane tool. Heterogeneity was evaluated using Cochran's Q test and the I2 statistic, and clinical heterogeneity was considered based on study design and population differences. Sensitivity analyses were conducted to test robustness of findings. RESULTS:Fifteen RCTs (1492 participants) were included. KP regimens significantly reduced total propofol use compared with FP (mean difference [MD] -0.42; 95% confidence interval [CI] -0.66 to -0.19; P = .0005), with greater benefit observed for esketamine (p for subgroup = 0.001). No significant differences were found in sedation (MD 0.01; 95% CI -0.40 to 0.43; P = .95) or pain scores (MD 0.24; 95% CI -0.18 to 0.65; P = .26). Safety outcomes were comparable across groups, with no significant differences in desaturation, nausea/vomiting, bradycardia, or tachycardia, except for hypotension, which was lower with KP (risk ratio [RR] 0.56; 95% CI 0.39 to 0.82; P = .003). Recovery and procedure times were similar between groups. CONCLUSIONS:Both KP and FP regimens are effective and safe for GI endoscopy. KP regimens reduce total propofol requirements and significantly lower the risk of hypotension, while showing comparable sedation quality, analgesia, and recovery profiles to FP. These findings suggest KP may offer safety and dosing advantages, though larger standardized trials are needed to confirm its clinical superiority.

ABSTRACT Background While oral anticoagulants (OACs) remain the cornerstone of stroke prevention, left atrial appendage closure (LAAC) is a potential alternative, particularly for patients with high bleeding risk or contraindications to long‐term anticoagulation. Methods Multiple databases were searched to identify relevant randomized controlled trials (RCTs), and four trials were shortlisted. Study selection, data extraction, and quality assessment were performed independently by two reviewers. Outcomes assessed included stroke (all, ischemic, hemorrhagic), systemic embolism, major bleeding, non‐procedure‐related bleeding, and mortality. Risk of bias was evaluated using Rob 2.0, and meta‐analyses were conducted using RevMan software. Dichotomous outcomes were reported as risk ratios (RR) while continuous outcomes were reported as mean differences (MD), with 95% confidence intervals (CIs). Results A total of 3116 participants were analyzed across outcomes. LAAC significantly reduced non‐procedure‐related bleeding (RR: 0.48, 95% CI: 0.37–0.61; p < 0.00001) and all‐cause mortality (RR: 0.74, 95% CI: 0.55–0.99; p = 0.04). A marginal reduction was observed in the composite outcome of stroke, systemic embolism, or death (RR: 0.77, 95% CI: 0.59–1.00; p = 0.05). No significant differences were found for major bleeding (RR: 0.82, 95% CI: 0.56–1.22), all strokes (RR: 0.84, 95% CI: 0.56–1.25), ischemic stroke (RR: 1.15, 95% CI: 0.72–1.85), hemorrhagic stroke (RR: 0.46, 95% CI: 0.11–2.02), systemic embolism (RR: 1.52, 95% CI: 0.36–6.41), or cardiovascular/unexplained death (RR: 0.60, 95% CI: 0.29–1.23). Conclusions LAAC offers a viable alternative to standard anticoagulation in selected AF patients with comparable efficacy and a particular benefit in reducing non–procedure‐related bleeding and mortality advantages.

Background Superficial dermatophytosis is a recurrent fungal infection affecting keratinized tissues, including the nails, skin, and hair. Recurrence and relapse of the disease remain major concerns despite advancements in antifungal treatment. Objective To examine the safety and effectiveness of oral itraconazole with isotretinoin therapy versus itraconazole monotherapy in patients with superficial dermatophytosis. Methods One hundred and twenty individuals with KOH-positive superficial dermatophytosis participated in a randomized clinical study. Group A received oral isotretinoin (20 mg once daily) along with oral itraconazole (100 mg twice daily) for eight weeks, whereas Group B received oral itraconazole (100 mg twice daily) alone. A 0-3 scale was used to assess the clinical severity of erythema, scaling, and pruritus. Liver function tests and lipid profiles were monitored at baseline and at 4-week intervals. Results After eight weeks treatments both groups showed considerable improvement in erythema, scaling, and pruritus (P<.001). Mean erythema scores decreased from 2.98±0.13 to 0.20±0.52 in Group A and from 2.92±0.28 to 0.25±0.43 in Group B, representing improvements of 93.3% and 91.4%, respectively. No statistically significant intergroup differences were observed. The side effects were minimal and self-limiting. Conclusion Although the combination of itraconazole and isotretinoin was well tolerated and safe, the outcomes were not statistically superior to those of itraconazole monotherapy. However, in severe or recurrent cases, isotretinoin may serve as a useful adjuvant by improving fungal clearance and increasing keratinocyte turnover.