COMPARATIVE STUDY OF EFFECT OF SWERTIA CHIRATA LEAF EXTRACT ON INDINAVIR TREATED RATS

Background: Indinavir is widely used for the treatment of human immunodeficiency virus (HIV) infection. It is known to cause hyperglycemia or insulin resistance and hyperlipidemia.Aim and Objectives: To study the effect of Swertia chirata leaf extract with metformin and pioglitazone on indinavir treated rats.Methods: Swiss albino rats were divided into five Groups of six animals each. All the groups (except control) were treated with indinavir 216 mg/kg (oral) for 15 days. Group I (control) received normal saline (oral) from day 8 to day 15, Group II received indinavir 216 mg/kg (oral), Group III received S. chirata plant extract 500 mg/kg (oral) from day 8 to day 15, Group IV received pioglitazone 4 mg/kg (oral) from day 8 to day 15, and Group V received metformin 36 mg/kg (oral) from day 8 to day 15. The biochemical parameters such as serum glucose, insulin, and lipid levels were measured on day 15. Results were analyzed using one-way analysis of variance followed by Bonferroni's multiple comparison test.Results: Indinavir (216 mg/kg) treated rats showed a significant (p<0.05) increase in glucose and insulin levels and also altered lipid levels. This indicates indinavir produces diabetic-like state in rats. S. chirata extract (500 mg/kg) decreases glucose and insulin levels and also improves lipid levels the effect is almost similar to metformin and pioglitazone.Conclusion: Indinavir causes elevated glucose, insulin and lipid levels, so care must be taken while prescribing indinavir for HIV patients. Treatment with S. chirata extract improved the altered glucose, insulin, and lipid profile in indinavir treated rats.Key words: Indinavir, Insulin resistance, Diabetes dyslipidemia, Glucose intolerance

Aerva lanata extract restores cellular viability and mitochondrial function against gentamicin induced nephrotoxicity on human embryonic kidney cells

Aerva lanata, commonly used in traditional medicine systems such as Ayurveda and Siddha, is well known for its diuretic and lithotriptic properties in the management of urolithiasis and other urinary tract disorders. However, despite its widespread traditional use, comprehensive studies elucidating the nephroprotective mechanisms of A. lanata under conditions of chemically induced renal damage remain limited, warranting further investigation. The current study investigated the nephroprotective properties of ethyl acetate extract of Aerva lanata (EA-AL) against gentamicin induced nephrotoxicity in human embryonic kidney (HEK293) cells. The initial phytochemical evaluation of EA-AL indicated the presence of tannins, which were later quantified. The antioxidant activity of EA-AL was evaluated using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay, while its nephroprotective activity was evaluated using the 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. The results demonstrated that EA-AL significantly restored cell viability in gentamicin-exposed cells. Gentamicin exposure induced oxidative stress, evidenced by increased lipid peroxidation products and diminished antioxidant enzyme levels. The levels of antioxidant enzymes were effectively elevated and membrane peroxidation was diminished through co-treatment with EA-AL. Moreover, 2\u27, 7’-Dichlorofluorescin diacetate (DCFDA) staining demonstrated that gentamicin exposure led to increased Reactive Oxygen Species ROS production, which was significantly reduced by EA-AL treatment. Exposure to gentamicin led to an elevation in depolarized viable and non-viable cells, indicating a disruption in mitochondrial membrane potential and overall mitochondrial integrity. The co-treatment with EA-AL successfully restored the population of viable cells. The reinstatement of cellular viability and mitochondrial function highlights the nephroprotective potential of EA-AL against imposed toxicity in HEK293cells

Internet Gaming Disorder Behaviors in emergent adulthood: a pilot study examining the interplay between anxiety and family cohesion

Understanding risk and protective factors associated with Internet Gaming Disorder (IGD) has been highlighted as a research priority by the American Psychiatric Association, (2013). The present study focused on the potential IGD risk effect of anxiety and the buffering role of family cohesion on this association. A sample of emerging adults all of whom were massively multiplayer online (MMO) gamers (18–29 years) residing in Australia were assessed longitudinally (face-to-face: N = 61, Mage = 23.02 years, SD = 3.43) and cross-sectionally (online: N = 64, Mage = 23.34 years, SD = 3.39). IGD symptoms were assessed using the nine-item Internet Gaming Disorder Scale-Short Form (IGDS-SF9; Pontes & Griffiths Computers in Human Behavior, 45, 137–143. https://doi.org/10.1016/j.chb.2014.12.006, 2015). The Beck Anxiety Inventory (BAI; Beck and Steer, 1990) and the balanced family cohesion scale (BFC; Olson Journal of Marital & Family Therapy, 3(1) 64–80. https://doi.org/10.1111/j.1752-0606.2009.00175.x, 2011) were applied to assess anxiety and BFC levels, respectively. Linear regressions and moderation analyses confirmed that anxiety increased IGD risk and that BFC weakened the anxiety-related IGD risk

Prefrontal response and frontostriatal functional connectivity to monetary reward in abstinent alcohol-dependent young adults

Although altered function in neural reward circuitry is widely proposed in models of addiction, more recent conceptual views have emphasized the role of disrupted response in prefrontal regions. Changes in regions such as the orbitofrontal cortex, medial prefrontal cortex, and dorsolateral prefrontal cortex are postulated to contribute to the compulsivity, impulsivity, and altered executive function that are central to addiction. In addition, few studies have examined function in these regions during young adulthood, when exposure is less chronic than in typical samples of alcohol-dependent adults. To address these issues, we examined neural response and functional connectivity during monetary reward in 24 adults with alcohol dependence and 24 psychiatrically healthy adults. Adults with alcohol dependence exhibited less response to the receipt of monetary reward in a set of prefrontal regions including the medial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex. Adults with alcohol dependence also exhibited greater negative correlation between function in each of these regions and that in the nucleus accumbens. Within the alcohol-dependent group, those with family history of alcohol dependence exhibited lower mPFC response, and those with more frequent drinking exhibited greater negative functional connectivity between the mPFC and the nucleus accumbens. These findings indicate that alcohol dependence is associated with less engagement of prefrontal cortical regions, suggesting weak or disrupted regulation of ventral striatal response. This pattern of prefrontal response and frontostriatal connectivity has consequences for the behavior patterns typical of addiction. Furthermore, brain-behavior findings indicate that the potential mechanisms of disruption in frontostriatal circuitry in alcohol dependence include family liability to alcohol use problems and more frequent use of alcohol. In all, these findings build on the extant literature on reward-circuit function in addiction and suggest mechanisms for disrupted function in alcohol dependence. © 2014 Forbes et al

Silver Lining Between Judicial Independence and Judicial Accountability in Judicial Appointments

The silver lining between judicial independence and judicial accountability in judicial appointments is the creation of an independent and transparent process that balances the need for judicial independence with the need for judicial accountability. Such a process would ensure that judges are appointed based on their qualifications and merit, while also providing ongoing evaluation and review of their performance to maintain public confidence in the legal system. This paper neither criticizes NJAC nor supports the current collegium system; rather it attempts to bring out a neutral judicial commission. In that reference, judicial commissions across the world have been examined. Being a developing country, India can learn from the pitfalls in judicial commissions of developed countries

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease

Sociodemographic and Visual Outcomes of Juvenile Idiopathic Arthritis Uveitis: IRIS&reg; Registry Study

Oliver Davidson,1,2 Anand E Rajesh,1,2 Marian Blazes,1,2 Ashley Batchelor,1,2 Aaron Y Lee,1,2 Cecilia S Lee,1,2,&ast; Laura C Huang1,3,&ast; On behalf of the IRIS® Registry Analytic Center Consortium1Department of Ophthalmology, University of Washington, Seattle, WA, USA; 2Roger and Angie Karalis Johnson Retina Center, Seattle, WA, USA; 3Division of Ophthalmology, Seattle Children’s Hospital, Seattle, WA, USA&ast;These authors contributed equally to this workCorrespondence: Laura C Huang, Department of Ophthalmology, Seattle Children’s Hospital and University of Washington, OA.9.220, 4800 Sand Point Way NE, Seattle, WA, USA, Tel +1 206-987-2177, Email [email protected]: Understanding sociodemographic factors associated with poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis may help inform practice patterns.Patients and Methods: Retrospective cohort study on patients < 18 years old who were diagnosed with both juvenile idiopathic arthritis and uveitis based on International Classification of Diseases tenth edition codes in the Intelligent Research in Sight Registry through December 2020. Surgical history was extracted using current procedural terminology codes. The primary outcome was incidence of blindness (20/200 or worse) in at least one eye in association with sociodemographic factors. Secondary outcomes included cataract and glaucoma surgery following uveitis diagnosis. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazards models.Results: Median age of juvenile idiopathic arthritis-associated uveitis diagnosis was 11 (Interquartile Range: 8 to 15). In the Cox models adjusting for sociodemographic and insurance factors, the hazard ratios of best corrected visual acuity 20/200 or worse were higher in males compared to females (HR 2.15; 95% CI: 1.45– 3.18), in Black or African American patients compared to White patients (2.54; 1.44– 4.48), and in Medicaid-insured patients compared to commercially-insured patients (2.23; 1.48– 3.37).Conclusion: Sociodemographic factors and insurance coverage were associated with varying levels of risk for poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis.Keywords: rheumatology, ophthalmology, uveitis, health inequity, social determinants of healt

CB2 Cannabinoid Receptors Contribute to Bacterial Invasion and Mortality in Polymicrobial Sepsis

BACKGROUND:Sepsis is a major healthcare problem and current estimates suggest that the incidence of sepsis is approximately 750,000 annually. Sepsis is caused by an inability of the immune system to eliminate invading pathogens. It was recently proposed that endogenous mediators produced during sepsis can contribute to the immune dysfunction that is observed in sepsis. Endocannabinoids that are produced excessively in sepsis are potential factors leading to immune dysfunction, because they suppress immune cell function by binding to G-protein-coupled CB(2) receptors on immune cells. Here we examined the role of CB(2) receptors in regulating the host's response to sepsis. METHODS AND FINDINGS:The role of CB(2) receptors was studied by subjecting CB(2) receptor wild-type and knockout mice to bacterial sepsis induced by cecal ligation and puncture. We report that CB(2) receptor inactivation by knockout decreases sepsis-induced mortality, and bacterial translocation into the bloodstream of septic animals. Furthermore, CB(2) receptor inactivation decreases kidney and muscle injury, suppresses splenic nuclear factor (NF)-kappaB activation, and diminishes the production of IL-10, IL-6 and MIP-2. Finally, CB(2) receptor deficiency prevents apoptosis in lymphoid organs and augments the number of CD11b(+) and CD19(+) cells during CLP. CONCLUSIONS:Taken together, our results establish for the first time that CB(2) receptors are important contributors to septic immune dysfunction and mortality, indicating that CB(2) receptors may be therapeutically targeted for the benefit of patients suffering from sepsis