Characterization of Salivary Glutathione reductase in Normal Individuals and its Implications on Smokers

Abstract: The assay of saliva is an increasing area of research with implications for basic and clinical purposes. Although this biological fluid is easy to manipulate and collect, careful attention must be directed to limit variation in specimen integrity. In this study, glutathione reductase (GR) activity of saliva obtained from smokers and non smokers of both the sex of various age groups were assessed. The investigation of salivary GR from non smokers revealed a pH optimum of 6.8, temperature optimum as 37ºC and a low K m of 0.058 mM for the substrate (Oxidized glutathione, GSSG). A significant reduction in the salivary GR activity has been observed from smokers of both acute and chronic than the non smokers. A drastic decrease in the GR activity was noticed in chronic smokers than the acute smokers, proving the possibility of utilizing the enzyme as a diagnostic biomarker for detecting the oral, throat and neck cancers. This optimized developed protocol was also found to be simple and cost effective

The effects of changes in glutathione levels through exogenous agents on intracellular cysteine content and protein adduct formation in chronic alcohol-treated VL17A cells

Alcohol-mediated liver injury is associated with changes in the level of the major cellular antioxidant glutathione (GSH). It is interesting to investigate if the changes in intracellular GSH level through exogenous agents affect the intracellular cysteine content and the protein adduct formation indicative of oxidative insult in chronic alcohol treated liver cells. In VL-17A cells treated with 2mM N-acetyl cysteine (NAC) or 0.1mM ursodeoxycholic acid (UDCA) plus 100mM ethanol, an increase in cysteine concentration which was accompanied by decreases in hydroxynonenal (HNE) and glutathionylated protein adducts were observed. Pretreatment of 100mM ethanol treated VL-17A cells with 0.4mM buthionine sulfoximine (BSO) or 1mM diethyl maleate (DEM) had opposite effects. Thus, altered GSH level through exogenous agents may either potentiate or ameliorate chronic alcohol-mediated protein adduct formation and change the cysteine level in chronic alcohol treated VL-17A cells. The gene expression of non-treated and ethanol-treated hepatocytes in 2 microarray datasets was also compared to locate differentially expressed genes involved in cysteine metabolism. The study demonstrates that increased protein adducts formation and changes in cysteine concentration occur under chronic alcohol condition in liver cells which may increase alcohol-mediated oxidative injury

Cost-effectiveness of janus kinase inhibitors for rheumatoid arthritis: A systematic review and meta-analysis of cost-utility studies

Introduction: Janus kinase inhibitors (JAK-i), a class of targeted synthetic disease-modifying antirheumatic drugs (tDMARDs), are suggested as second or third-line therapies in rheumatoid arthritis (RA). Synthesized cost-effective evidence would aid in informed decision-making given the similar clinical effectiveness of JAKi, but incongruent cost-effectiveness reports.Methods: Literature search was conducted in PubMed, Embase, Scopus, and Tufts Medical Centers’ cost-effective analysis registry. We pooled the incremental net benefit (INB) with 95% confidence interval (CI) using random-effects model and the heterogeneity was assessed using Cochrane-Q test and I2 statistic. Modified economic evaluation bias checklist was used to assess the quality of selected studies. Publication bias was assessed using a funnel plot and Egger’s test. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) assessment was performed to assess the certainty of outcomes presented.Results: We included seventeen relevant studies for systematic review, of which fifteen were eligible for meta-analysis. The meta-analysis results showed that JAK-i is cost-effective compared to csDMARDS/bDMARDs with a pooled INB (INBp) of $19,886 (95$23,144 (74.1–46,214) and high heterogeneity (I2 = 99.67). But on a separate analysis JAK-i as second-line treatment is not cost-effective than TNF-a-i (INBp = $25,813, -5,714 to 57,340). However, leave-one-out analysis found that omitting a single outlier makes JAK-i cost-effective. Further, JAK-i is not cost-effective as a third-line treatment for csDMARD-TNF-a-I failed RA, compared to csDMARDs/bDMARDs with INBp$26,157 (-7,284 to 59,598).Conclusion: Meta-analysis suggests that JAK-i is cost-effective when used after csDMARD failure but not cost-effective when used after csDMARD-TNF-a-i failure with low certainty of evidence.Clinical Trial Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021222541, identifier CRD4202122254

Ionic thermo currents in doped CsBr and KCI

The reorientation of dipolar complexes in Ca2+, Pb2+, Ba2+, MnO24- doped CsBr single crystals and in CrO24- doped KC1 single crystals are reported in this article. The ionic thermo-current peaks were analysed using different methods. The reorientation parameters — the activation energy and the frequency factor — are calculated in each case. The results pertaining to the molecular impurities are found to be interesting.On étudie par la méthode des thermocourants de dépolarisation la réorientation des complexes lacune-impureté dans les monocristaux de CsBr dopés par Ca 2+, Pb2+, Ba2+, MnO24 - et KC1 dopés par CrO24- . Les pics de thermocourant sont analyses par différentes méthodes. Dans chaque cas, l'énergie d'activation et les facteurs pré-exponentiels sont calcules. Les résultats obtenus pour les impuretés MnO24 - et CrO42- sont très intéressants

The effects of changes in glutathione levels through exogenous agents on intracellular cysteine content and protein adduct formation in chronic alcohol-treated VL17A cells

Alcohol-mediated liver injury is associated with changes in the level of the major cellular antioxidant glutathione (GSH). It is interesting to investigate if the changes in intracellular GSH level through exogenous agents affect the intracellular cysteine content and the protein adduct formation indicative of oxidative insult in chronic alcohol treated liver cells. In VL-17A cells treated with 2mM N-acetyl cysteine (NAC) or 0.1mM ursodeoxycholic acid (UDCA) plus 100mM ethanol, an increase in cysteine concentration which was accompanied by decreases in hydroxynonenal (HNE) and glutathionylated protein adducts were observed. Pretreatment of 100mM ethanol treated VL-17A cells with 0.4mM buthionine sulfoximine (BSO) or 1mM diethyl maleate (DEM) had opposite effects. Thus, altered GSH level through exogenous agents may either potentiate or ameliorate chronic alcohol-mediated protein adduct formation and change the cysteine level in chronic alcohol treated VL-17A cells. The gene expression of non-treated and ethanol-treated hepatocytes in 2 microarray datasets was also compared to locate differentially expressed genes involved in cysteine metabolism. The study demonstrates that increased protein adducts formation and changes in cysteine concentration occur under chronic alcohol condition in liver cells which may increase alcohol-mediated oxidative injury

Household catastrophic health expenditures for rheumatoid arthritis: a single centre study from South India

Abstract Rheumatoid arthritis (RA) not only has a physical and emotional toll but also has a substantial economic impact. This study aims to estimate the burden of catastrophic health expenditure (CHE) on households due to RA in Tamil Nadu, India. We conducted cross-sectional descriptive hospital-based single-centre study at a tertiary care private multispecialty hospital in Tamil Nadu, India. The study comprised 320 RA patients who visited the outpatient clinic from April to October 2022. Demographic and baseline descriptive characteristics were reported. Multivariable logistic regression analyses were performed to identify major determinants associated with CHE. We also examined the inequality in household annual income and CHE. Most study participants were females (88.1%) with a mean age (SD) of 55.57 ± 12.29 years. About 93% of RA patients were from urban areas, and 89.4% were literate. Only 8.1% of respondents reported having health insurance. Households experiencing CHE owing to RA were 51.4% (n = 162). The mean (95% CI) annual health expenditure for treating RA is ₹44,700 (₹41,710 to 47,690) with a median (IQR) of ₹39,210 (₹25,500) [$476 ($310)]. The corresponding mean (95% CI) and median (IQR) Out of pocket expenditure among RA patients per household were ₹40,698 (₹38,249 to 43,148) [$494 ($464 to $524)] and ₹36,450 (23,070) [$442 ($280)] respectively. Nearly half of the households with RA patients had a financial catastrophe due to healthcare costs being paid out-of-pocket and limited health insurance coverage. The results underscore the need for comprehensive approaches to strengthening public health policies along with financial risk protection and quality care in India

Oxidation in water-trees grown in field-aged cables

In order to detect oxidation in water trees, the authors performed micro-FTIR spectroscopy and oxidative induction time (OIT) measurements in many trees grown in various field-aged distribution cables. It is concluded that there is no definitive evidence that oxidation affects water-tree initiation in field-aged cross-linked polyethylene cables. It is found, in fact, that trees may be less oxidized than untreed insulations. It seems that the reduced OIT values of aged cables correspond to reduced antioxidant content.NRC publication: Ye