ABSTRACT:Parkinson's disease (PD) is an incurable progressive neurodegenerative condition, which is characterized by a selective loss of dopaminergic neurons in the substantia nigra and subsequent development of motor impairment along with a non-motoric syndrome. It has a multifactorial etiopathogenesis, including oxidative stress, mitochondrial failure, lasting neuroinflammation, and α-synuclein aggregation. Interestingly, acetoside and arbutin are naturally occurring phenolic glycosides that have gained increased attention in recent times due to their strong antioxidant, anti-inflammatory, and neuroprotective capabilities. These agents have been empirically demonstrated to reduce reactive oxygen species, energize endogenous antioxidant defenses such as superoxide dismutase, catalase (CAT), glutathione, maintain mitochondrial integrity, and salvage adenosine triphosphate (ATP) generation. Furthermore, they inhibit pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), prevent the activation of caspase-3 and lipid peroxidation, regulate AMP-activated protein kinase and p62 signaling pathways, and alleviate the loss of dopaminergic neurons, which results in improved motor performance. Computational docking reports have revealed positive results between arbutin, acetoside, and key targets of PD (e.g., acetylcholinesterase [AChE], TNF-α, caspase-3, CAT, dopamine-associated proteins, and α-synuclein). Arbutin showed binding energies of - 7.6 kcal/mol (AChE), -7.0 kcal/mol (caspase-3), -9.0 kcal/mol (CAT), -8.8 kcal/mol (TNF-α), and - 7.0 kcal/mol (dopaminergic targets). In contrast, acetoside showed stronger interactions with corresponding targets, exhibiting binding energies of - 8.7 kcal/mol, -8.9 kcal/mol, -9.7 kcal/mol, and - 8.9 kcal/mol. Collectively, these findings highlight phenolic glycosides as promising multitarget neuroprotective candidates for PD.
ABSTRACT:We report a 47-year-old human immunodeficiency virus-positive male with disseminated tuberculosis who developed recurrent maculopapular eruptions with mucosal involvement following exposure to multiple drugs, including diclofenac, rifampicin, and fluoroquinolones. Sequential drug rechallenge strongly implicated fluoroquinolones and rifampicin. He was successfully managed with systemic corticosteroids, intravenous immunoglobulin, and careful sequential reintroduction of nonculprit anti-tubercular therapy drugs. This case highlights the importance of drug reintroduction and cautious use of fluoroquinolones and rifampicin in immunocompromised patients.
BACKGROUND:Antimicrobial resistance has emerged as a global challenge to human health, primarily due to inappropriate use. The ICMR reports revealed that there is sustained rise of AMR in India. OBJECTIVE:The objective of this study was to evaluate the prescribing pattern of antimicrobials and rationality of empiric antimicrobial use in a tertiary care hospital. METHOD:A prospective observational study, approved by the Institutional Ethical Committee (IEC) was conducted for a period of one year from July 2023 to June 2024 among the admitted patients of the hospital. The prescribing pattern was assessed in accordance with AWaRe classification and prescribing indicators by the World Health Organization. Rational use of empiric therapy was assessed as per the ICMR 2022 guidelines. RESULTS:A total of 653 antimicrobials were prescribed to 289 patients and maximum antimicrobials were from Watch category (55.7%), followed by Access (40.4%), and Reserve category (2.3%). The respiratory tract infection was the most common indication to start empiric antimicrobial therapy. The empiric therapy was appropriate for 80.3% patients as per the ICMR guidelines. The observed deviations were the empiric use of amikacin for bone & joint infection, duplicate beta lactam therapy, 3rd generation cephalosporins for uncomplicated urinary tract infection, the use of Reserve antibiotic-linezolid, and the use of piperacillin/tazobactam for sepsis patients. CONCLUSION:There is a need to strengthen the antimicrobial stewardship program by adhering to the national guidelines in the hospital settings, to prevent antimicrobial misuse and resistance. The use of Assess category should be encouraged, Watch category should be used under proper monitoring and the use of Reserve antimicrobials as an empiric therapy should be avoided.
ABSTRACT:Fixed drug eruptions (FDE) are drug-induced skin reactions that repeatedly occur at the same anatomical site. The skin lesions are usually clear hyperpigmented patches that may develop into blisters. The skin response involves type IV delayed hypersensitivity reactions and is caused by drug-specific memory CD8 T-cells located at the affected skin site. Levocetirizine, an H1-selective second-generation piperazine antihistamine, has a good safety profile and is used to treat the skin reactions. Its nonprescription availability leads to self-medication and unrecognised adverse drug reactions (ADR). FDE due to levocetirizine, as well as with cetirizine, is less common in the literature. This case was reported to our ADR Monitoring Center and causality was assessed as probable and preventable. This case shows that antihistamines such as levocetirizine can trigger FDE in susceptible individuals. Improving clinical awareness through robust Pharmacovigilance activities, educating patients about triggers, and discouraging self-medication are crucial for preventing recurrence.
BACKGROUND:Tributyltin chloride (TBTC) is an organotin (OT) compound, a known neurotoxin and an endocrine disruptor, but it is inadequately characterized for its short-term exposure. This study aimed to explore the role of N-acetylcysteine (NAC) and Eplerenone in TBTC induced neurotoxicity in rats. MATERIALS AND METHODS:Rats were exposed to a single dose of TBTC and were behaviorally assessed on open field test, light and dark box, Morris water maze, and rota rod test. Thiobarbituric acid reactive substances (TBARS) and nitrite were estimated as a measure of oxidative and nitrosative stress. Evans blue extravasation was used to assess the blood-brain barrier (BBB) integrity and morphological changes were assessed by histopathology. NAC (50 mg/kg) was used as a standard treatment, and eplerenone (50 and 100 mg/kg) was used as test interventions. RESULTS:Short-term TBTC exposure produced significant anxiety-like behavioral alterations, accompanied by elevated brain TBARS and serum nitrite levels, indicating enhanced oxidative and nitrosative stress. BBB integrity was disrupted, and histopathological examination revealed early structural changes. Treatment with NAC and Eplerenone significantly attenuated behavioral disturbances, oxidative stress markers, BBB disruption, and histopathological damage. In contrast, no significant deficits were observed in spatial memory or motor coordination, likely due to the limited exposure duration. CONCLUSION:TBTC induced early neurotoxic changes in the brain, which were attenuated by NAC and eplerenone administration. The beneficial effects support for further mechanistic studies on mineralocorticoid receptor modulation as a potential target for OT-induced neurotoxicity.
ABSTRACT:Obesity is now recognized as a chronic, multifactorial, and progressive disease as opposed to mere excess of body weight. It significantly increases the risk of type 2 diabetes, cardiovascular disease, metabolic-associated fatty liver disease, and mental health disorders. 2022 data reveal that nearly 3 billion individuals worldwide were living with either obesity or overweight. Pharmacological therapy has evolved remarkably. Earlier medications targeted primarily the brain's monoaminergic pathways but they were withdrawn due to safety concerns. Currently, six medications (Orlistat, Phentermine/Topiramate, Naltrexone/Bupropion, Liraglutide, Semaglutide, and Tirzepatide) are approved by the U.S. Food and Drug Administration for long-term obesity management and among these, glucagon-like peptide receptor agonists have revolutionized the therapy. The emerging pipeline is even more promising. It has new dual and triple combinations such as CagriSema, Survodutide, and Retatrutide for better efficacy and metabolic outcomes, as well as long-acting and oral formulations, which will improve adherence and accessibility. India released its new obesity guideline in January 2025, emphasizing on early pharmacotherapy initiation and the adoption of stage-based obesity classification. Together, these developments signify a transformative era in obesity care where pharmacotherapy is a powerful and evidence-based tool that, in many cases, approaches the efficacy and metabolic benefits traditionally associated with bariatric surgeries.
CONTEXT:Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system, where demyelination occurs alongside axonal and neuronal degeneration. Current treatments focus primarily on immunomodulation and symptom management, with limited efficacy in halting or reversing demyelination. Finding drugs to treat progression of the disease remains the greatest unmet need for people with MS. MATERIALS AND METHODS:Demyelination is induced in Swiss albino mice by administering cuprizone (CPZ) 0.3% in the diet for 6 weeks. Two different doses (1.2 and 2.4 mg/kg) of flunarizine dihydrochloride were administered orally along with CPZ for a duration of six weeks. We used the rotarod apparatus and actophotometer to assess motor and locomotor activity, elevated plus maze to evaluate anxiety, and shuttle box apparatus to evaluate memory. Various biochemical parameters were estimated from brain homogenate, and the histological changes were evaluated using H and E and Luxol Fast Blue stain. The experimental data obtained were analysed by ANOVA followed by the Tukey multiple comparison test. RESULTS:The result of behavioural assays showed better motor coordination, locomotion, memory, and reduced anxiety levels in the drug-treated mice. Besides, the elevated level of serotonin and the reduced levels of glutamate and catalase level in the brain homogenate of treated mice indicate its neuroprotective potential. Healthy histology appearance and increased level of myelin in the brain also substantiate the protective effect of Flunarizine. CONCLUSIONS:Our experimental data suggest that flunarizine dihydrochloride attenuated the demyelination in the brain and also produced functional and behavioural improvement in demyelinated mice, suggesting its potential to manage demyelinating disorders.
ABSTRACT:In the current directive of the National Medical Commission, postgraduate (PG) residents are required to list their dissertation topics within a very short period after enrollment. Such activity to pre-establish shortlisted topics before subjecting them to any training in research methodology results in designed studies that are not executed well, and students are not interested. In this study, the author suggests that a 3-month reflection window is necessary to place the interest of the students in line with scientific research.
ABSTRACT:The distribution of CYP2C19 polymorphisms and associated metabolizer phenotypes varies across populations. There is a lack of large scale pooled data on CYP2C19 polymorphisms and associated metabolizer phenotypes in Indian population. This systematic review and meta analysis aimed to determine the prevalence of CYP2C19 loss of function and gain of function polymorphisms (*2, *3, and *17) and their associated genotype predicted metabolizer phenotypes in the Indian population. A systematic literature search was conducted in electronic databases to identify relevant studies reporting CYP2C19 polymorphisms in individuals of Indian origin. Observational studies employing validated genotyping methods were included. Meta analysis was performed using a random effects model with double arcsine transformation to estimate pooled prevalence with 95% confidence intervals (CI). Subgroup analyses were conducted based on geographical regions of India, and heterogeneity was assessed using the I2 statistic. A total of 31 studies were included in the analysis. The pooled prevalence of the CYP2C19*2 allele was 32% (95% CI: 28%-37%), with the highest prevalence observed in South India. The CYP2C19*3 allele was rare, with a pooled prevalence of 1% (95% CI: 0%-1%). The gain of function allele CYP2C19*17 showed a prevalence of 17% (95% CI: 13%-21%), with the highest frequency in North India. The pooled prevalence of poor metabolizers was 16% (95% CI: 11%-22%), whereas ultra rapid metabolizers accounted for 12% (95% CI: 4%-24%) of the population. Substantial regional variability in allele frequencies and metabolizer phenotypes was observed. The distribution of CYP2C19 polymorphisms and metabolizer phenotypes shows considerable regional variability within the Indian population.
BACKGROUND:Studying the pleiotropic effects of medicines can reveal their unexplored therapeutic advantages. It promotes repurposing established drugs or identifying compounds that affect multiple targets. The widely prescribed antihypertensive agents, ramipril and olmesartan, because of their ability to reduce C-reactive protein activity, may also modulate the immune system. AIM:The study aims to demonstrate the potential immunomodulatory effects of ramipril and olmesartan, which would be beneficial for the management of inflammation in patients with coexisting hypertension. MATERIALS AND METHODS:The anti-inflammatory properties of the drugs were studied in acute and chronic models of inflammation. The immunomodulatory action was evaluated using a neutrophil adhesion test, proinflammatory and anti-inflammatory cytokine assay, and hemagglutination antibody titer assay. Histopathological analyses of rat paw edema were also performed. RESULTS:Both drugs demonstrated enhanced neutrophil adhesion, increased hemagglutination antibody titers, reduced paw edema, and improvement in cellular and structural changes associated with inflammation. Drug treatment also inhibited proinflammatory cytokine production while promoting anti-inflammatory cytokine production. CONCLUSION:The results indicate the immunomodulatory potential of ramipril and olmesartan at equipotent antihypertensive doses, compared with the standard drugs, in Wistar albino rats. The results reveal that olmesartan exhibits superior immunomodulatory properties compared with Ramipril.
ABSTRACT:Paraquat is a highly toxic bipyridyl herbicide that continues to be used in several countries despite restrictions elsewhere. While ingestion is the most common route of poisoning, intravenous administration is rare and associated with extremely high mortality. We report the case of a 26-year-old male who attempted suicide by self-injecting 10 mL of 24% paraquat dichloride intravenously into the dorsal metacarpal region. Within hours, he developed hematemesis, diaphoresis, giddiness, chills, agitation, and diffuse burning sensations. On admission, he was alert but drowsy with bradycardia, pedal edema, and local swelling at the injection site. Laboratory findings revealed leukocytosis, elevated serum creatinine, hypokalemia, and metabolic acidosis. Despite early hemodialysis, continuous renal replacement therapy, and administration of antioxidants and supportive treatment, the patient developed progressive respiratory distress, refractory hypotension, and recurrent cardiac arrests. He died 28 h after admission. Intravenous paraquat poisoning is rare but uniformly fatal. This case emphasizes the importance of early recognition, aggressive supportive care, and the continued need for preventive strategies and regulatory measures to limit paraquat availability.
INTRODUCTION:Traditional live demonstrations were found to be insufficient in supporting the long-term retention and reproducibility of practical skills among medical students. Thus, we adopted a blended learning approach that included self-created demonstration videos. STUDY OBJECTIVES:To determine the effectiveness of using a quick response (QR) code linked to prerecorded demonstration videos for various objective structured practical examination (OSPE) stations by baseline and post innovation test scores and to obtain students' feedback on this innovative teaching approach. MATERIALS AND METHODS:Following IRB approval and informed consent, the students were trained in small-group live demonstrations of OSPE stations. Then, a baseline OSPE assessment (pretest) was done. Instructional demonstration videos on different routes of drug administration were created following a structured checklist. This was linked to a QR code. After 2 months, these videos were uploaded to Google Drive for student access. This was followed by a posttest and students' feedback. Statistical analysis was done using a paired t-test, and a P < 0.05 was considered significant. RESULTS:The posttest scores of 17.54 ± 2.18 (mean ± standard deviation [SD]) demonstrated a significant improvement in student performance compared to the pretest scores of 11.95 ± 6.69 (mean ± SD), with a P < 0.001. In the feedback, a majority (>95%) of students reported that the QR code-linked demonstration videos improved their comprehension of OSPE techniques, agreed that blended learning improved their understanding, and recommended these videos for subsequent batches. CONCLUSION:This integrated video-assisted model holds promise for broader application across medical curricula, aiming to enhance skill retention and learner autonomy.
BACKGROUND:Schizophrenia has traditionally been conceptualized through dopaminergic and glutamatergic frameworks. In recent years, attention has increasingly focused on the role of immune dysregulation in its pathophysiology, although conclusive evidence remains limited. In this context, the present study aimed to investigate alterations in cytokine profiles and their association with clinical symptomatology following treatment with atypical antipsychotics for 8 weeks. MATERIALS AND METHODS:Thirty patients aged 18-65 years, diagnosed with schizophrenia as per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, were enrolled. Participants received atypical antipsychotic therapy as clinically indicated. Symptom severity was assessed using the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS). Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), and regulated upon activation, normal T-cell expressed and secreted (RANTES) were measured at baseline and after 8 weeks of therapy. RESULTS:Median SAPS and SANS scores significantly decreased from 39 to 30.5 (P < 0.001) and from 30 to 28 (P < 0.001), respectively. Correspondingly, median serum TNF-α levels declined from 28.55 (6.51-227) to 19.98 (4.56-145) pg/mL (P = 0.033). Reductions were also observed for IL-8 (62.2-50.25 pg/mL; P = 0.171) and RANTES (520-500 pg/mL; P = 0.758). CONCLUSION:Treatment with atypical antipsychotics significantly attenuated both positive and negative symptoms and reduced TNF-α levels in patients with schizophrenia. The concomitant decline in cytokine concentrations suggests a potential immunomodulatory effect of treatment, highlighting TNF-α, IL-8, and RANTES as possible prognostic biomarkers.
BACKGROUND AND OBJECTIVES:Sickle cell disease (SCD) is characterized by chronic hemolysis, inflammation, oxidative stress, and recurrent vaso-occlusive complications leading to significant morbidity. Hydroxyurea (HU), a widely used disease-modifying therapy, increases fetal hemoglobin (HbF) and reduces clinical complications. Emerging evidence suggests additional anti-inflammatory and antioxidant effects. The objectives of this study were to compare the inflammatory markers, oxidative stress markers, hematological parameters, and quality of life from baseline to 6 months after HU therapy among patients with SCD. MATERIALS AND METHODS:In this prospective observational study, 16 HU-naïve patients with SCD were evaluated at baseline and after 6 months of HU therapy. Investigations included inflammatory markers (interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-α]), oxidative stress markers (malondialdehyde [MDA] and glutathione [GSH]), hematological parameters (HbF, sickle hemoglobin [HbS], leukocyte count, and neutrophil-to-lymphocyte ratio [NLR]), and quality of life assessed using the 36-Item Short Form Health Survey questionnaire. RESULTS:Significant reductions in inflammatory markers were observed, with TNF-α decreasing from 5.82 ± 2.82 pg/mL to 4.64 ± 2.65 pg/mL (P = 0.006) and median IL-6 levels decreasing from 6.32 to 4.42 pg/mL (P = 0.001). Oxidative stress improved, with reduced MDA levels (P = 0.011) and increased GSH levels (P = 0.001). Hematological parameters showed significant improvement, including increased HbF and reductions in HbS, leukocyte count, and NLR (P < 0.001). HU therapy was well tolerated, with good compliance, improved quality of life, and a low incidence of complications. CONCLUSION:HU may exert therapeutic benefit not only by increasing HbF but also through anti-inflammatory and antioxidant effects, leading to improved hematological stability and fewer complications in SCD.
BACKGROUND:While both clopidogrel and prasugrel inhibit platelet aggregation, their comparative pleiotropic effects on inflammatory and oxidative stress markers remain unclear. OBJECTIVE:To compare the anti-inflammatory and antioxidant potential of clopidogrel and prasugrel given as dual antiplatelet therapy (DAPT) along with aspirin in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). SUBJECTS AND METHODS:In this prospective cohort study, patients aged 18-65 years undergoing PCI for ACS and eligible candidates for DAPT were included. The two study groups were: aspirin + clopidogrel (AC group; n = 52) and aspirin + prasugrel (AP group; n = 52). A change in inflammatory (high-sensitivity C-reactive protein [hs-CRP]) and oxidative stress (total antioxidant capacity [TAOC]) markers at 4 weeks was compared to baseline in two groups. RESULTS:A total of 90 patients (46 in AC group and 44 in AP group) completed the study and were included in the analysis. AP group demonstrated a significantly greater reduction in hs-CRP levels at 4 weeks compared to AC group (-7.17 ± 5.95 in AP vs. -4.10 ± 3.81 mg/L in AC groups, P = 0.002). A relatively greater increase in TAOC was also seen in AP group though statistically insignificant (184.25 ± 274.03 in AP vs. 126.67 ± 198.49 in AC groups, P = 0.117). Bleeding and adverse events were comparable in two groups. CONCLUSIONS:Prasugrel-based DAPT showed significantly greater reduction in inflammation compared to clopidogrel-based DAPT, with comparable antioxidant benefit and hematological safety indicating a greater pleiotropic benefit of prasugrel than clopidogrel.
