Evaluation and Comparative study of Lens Aldose Reductase Inhibitory activity of leaves Extracts of Merremia emarginata, Permotrema perlatum, Tridax procumbens and Euphorbia prostrata: Potential for Diabetic Cataract treatment

Introduction: The present research attempts at discovering an effective anti-cataract agent, focusing on evaluation of Aldose reductase inhibition (ARI) capacities of weeds and lichen. The present study was aimed at finding out the in vitro ARI activity of extracts of weed plants and lichen. Methods: ARI activities of the ethanolic extract of weed plants and lichen were evaluated using goat lens aldose reductase using Hayman and Kinoshita method. Evaluation was done using UV-Visible spectroscopy at 340 nm. Results: The extracts showed AR inhibitory activity at different extent. Conclusion: The study concludes the ARI capacity of leaves of Merremia emarginata, Permotrema perlatum, Tridax procumbens and Euphorbia prostrata which may be attributed to their flavonoid constituents and their extraction are solvent dependent. Thus Merremia emarginata leaves, Permotrema perlatum, Tridax procumbens and Euphorbia prostrata weed plant’s leaves and lichen may therefore work as a base for the development of anticataract agent. And out of all extract Triadax procumbens showed maximum activity. Keywords: Aldose reductase, Merremia emarginata leaves, Permotrema perlatum, Tridax procumbens and Euphorbia prostrata anti-cataract agent, weed plant, lichen, flavonoid

An open study to evaluate the efficacy and safety of tazarotene gel (0.1%) in acne vulgaris

BACKGROUND: Tazarotene is a new third generation topical acetylenic retinoid. The present study was conducted to evaluate the efficacy and safety of tazarotene gel (0.1%) in Indian patients of acne vulgaris. METHODS: The present study was a prospective, open, multicentric, phase III trial. The duration of study was 14 weeks, including a 12-week active treatment period, preceded by a 2-week washout phase. Patients applied 0.1% tazarotene gel as a thin film over the affected area once daily in the evening. The efficacy was evaluated by analyzing changes in the number of facial acne lesions and patient's and physicians' global assessment. The efficacy parameters were assessed at baseline, visits 2, 4, 8, and 12 weeks. Tolerability and safety was assessed by physical examination, laboratory parameters and evaluation of adverse events. RESULTS: A total of 126 patients in 6 centers completed the study. At the end of the 8th and 12th weeks, the mean number of inflammatory lesions reduced by 70.6% and 86.1%, non-inflammatory lesions by 81.5% and 92%, and total lesion count 75.6% and 88.8% respectively from baseline. Also, 90.7% and 93.6% of total study cases showed complete to moderate clearance of acne lesions according to physicians at the end of the 8th and 12th weeks. CONCLUSIONS: This study confirms the efficacy and safety of tazarotene gel (0.1%) in Indian patients of acne vulgaris

Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial

<div><p>Background</p><p>Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2) is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1) and has been shown to increase renal perfusion in healthy human volunteers. We hypothesized that serelaxin could ameliorate renal vasoconstriction and renal dysfunction in patients with cirrhosis and portal hypertension.</p><p>Methods and findings</p><p>To establish preclinical proof of concept, we developed two independent rat models of cirrhosis that were characterized by progressive reduction in renal blood flow and glomerular filtration rate and showed evidence of renal endothelial dysfunction. We then set out to further explore and validate our hypothesis in a phase 2 randomized open-label parallel-group study in male and female patients with alcohol-related cirrhosis and portal hypertension. Forty patients were randomized 1:1 to treatment with serelaxin intravenous (i.v.) infusion (for 60 min at 80 μg/kg/d and then 60 min at 30 μg/kg/d) or terlipressin (single 2-mg i.v. bolus), and the regional hemodynamic effects were quantified by phase contrast magnetic resonance angiography at baseline and after 120 min. The primary endpoint was the change from baseline in total renal artery blood flow.</p><p>Therapeutic targeting of renal vasoconstriction with serelaxin in the rat models increased kidney perfusion, oxygenation, and function through reduction in renal vascular resistance, reversal of endothelial dysfunction, and increased activation of the AKT/eNOS/NO signaling pathway in the kidney. In the randomized clinical study, infusion of serelaxin for 120 min increased total renal arterial blood flow by 65% (95% CI 40%, 95%; <i>p <</i> 0.001) from baseline. Administration of serelaxin was safe and well tolerated, with no detrimental effect on systemic blood pressure or hepatic perfusion. The clinical study’s main limitations were the relatively small sample size and stable, well-compensated population.</p><p>Conclusions</p><p>Our mechanistic findings in rat models and exploratory study in human cirrhosis suggest the therapeutic potential of selective renal vasodilation using serelaxin as a new treatment for renal dysfunction in cirrhosis, although further validation in patients with more advanced cirrhosis and renal dysfunction is required.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01640964" target="_blank">NCT01640964</a></p></div

An open study to evaluate the efficacy and safety of tazarotene gel (0.1%) in acne vulgaris

BACKGROUND: Tazarotene is a new third generation topical acetylenic retinoid. The present study was conducted to evaluate the efficacy and safety of tazarotene gel (0.1%) in Indian patients of acne vulgaris. METHODS: The present study was a prospective, open, multicentric, phase III trial. The duration of study was 14 weeks, including a 12-week active treatment period, preceded by a 2-week washout phase. Patients applied 0.1% tazarotene gel as a thin film over the affected area once daily in the evening. The efficacy was evaluated by analyzing changes in the number of facial acne lesions and patient's and physicians' global assessment. The efficacy parameters were assessed at baseline, visits 2, 4, 8, and 12 weeks. Tolerability and safety was assessed by physical examination, laboratory parameters and evaluation of adverse events. RESULTS: A total of 126 patients in 6 centers completed the study. At the end of the 8th and 12th weeks, the mean number of inflammatory lesions reduced by 70.6% and 86.1%, non-inflammatory lesions by 81.5% and 92%, and total lesion count 75.6% and 88.8% respectively from baseline. Also, 90.7% and 93.6% of total study cases showed complete to moderate clearance of acne lesions according to physicians at the end of the 8th and 12th weeks. CONCLUSIONS: This study confirms the efficacy and safety of tazarotene gel (0.1%) in Indian patients of acne vulgaris

Study - Evaluation of the efficacy, safety and tolerability of tacrolimus ointment in Indian patients of moderate to severe atopic dermatitis: A multicentric, open label, phase III study

Aim of study: Tacrolimus, a topical immunomodulator, has been introduced as a new treatment for moderate to severe atopic dermatitis. The present study was conducted to evaluate the efficacy, safety and tolerability of Tacrolimus ointment in patients of atopic dermatitis in an Indian setting. Methods: The present study was a prospective, open, multicentric, Phase III trial.The duration of study was 5 weeks, including a 3-week active treatment period, preceded by a 1-week washout phase and followed by a 1-week follow-up phase. Patients diagnosed to be suf fering from moderate to severe atopic dermatitis as per the Rajka and Langeland criteria were treated with Tacrolimus ointment 0.03% twice daily. Efficacy was assessed by modified Eczema Area Sensitivity Index (mEASI) score, patient’s and physician’s global assessment. Tolerability and safety was assessed by physical examination, laboratory parameters and evaluation of adverse events. Results: There was a statistically significant decrease in the modified Eczema Area Sensitivity Index (mEASI) score (P<0.05). Patient’s and Physician’s global evaluation of treatment was complete resolution to very good improvement in most of the patients. The laboratory values were within normal limits. The drug was well tolerated. Conclusions: This study confirms the efficacy and safety of Tacrolimus ointment 0.03% in Indian patients of moderate to severe atopic dermatitis

Operational Forest-Fire Spread Forecasting Using the WRF-SFIRE Model

In the present research, the open-source WRF-SFIRE model has been used to carry out surface forest fire spread forecasting in the North Sikkim region of the Indian Himalayas. Global forecast system (GFS)-based hourly forecasted weather model data obtained through the National Centers for Environmental Prediction (NCEP) at 0.25 degree resolution were used to provide the initial conditions for running WRF-SFIRE. A landuse–landcover map at 1:10,000 scale was used to define fuel parameters for different vegetation types. The fuel parameters, i.e., fuel depth and fuel load, were collected from 23 sample plots (0.1 ha each) laid down in the study area. Samples of different categories of forest fuels were measured for their wet and dry weights to obtain the fuel load. The vegetation specific surface area-to-volume ratio was referenced from the literature. The atmospheric data were downscaled using nested domains in the WRF model to capture fire–atmosphere interactions at a finer resolution (40 m). VIIRS satellite sensor-based fire alert (375 m spatial resolution) was used as ignition initiation point for the fire spread forecasting, whereas the forecasted hourly weather data (time synchronized with the fire alert) were used for dynamic forest-fire spread forecasting. The forecasted burnt area (1.72 km2) was validated against the satellite-based burnt area (1.07 km2) obtained through Sentinel 2 satellite data. The shapes of the original and forecasted burnt areas matched well. Based on the various simulation studies conducted, an operational fire spread forecasting system, i.e., Sikkim Wildfire Forecasting and Monitoring System (SWFMS), has been developed to facilitate firefighting agencies to issue early warnings and carry out strategic firefighting

Effect of acute serelaxin treatment on renal blood flow and tissue oxygenation in CCl₄ cirrhotic rats.

<p>Renal blood flow (RBF, A) and mean arterial pressure (MAP, B) responses to acute i.v. serelaxin (4 μg) or vehicle in 16-wk CCl₄ rats (<i>n =</i> 5–7). Measurement of velocity time integral (C) and renal resistive index (D) following acute i.v. serelaxin (4 μg) or vehicle (<i>n =</i> 6–8). Deoxygenated hemoglobin levels (R2*) in renal medulla in 8-wk (E) and 16-wk (F) CCl₄ rats at baseline, 30 min, and 60 min following acute i.v. serelaxin (4 μg) or vehicle (<i>n =</i> 5–8). Data presented as mean ± standard error of the mean, analyzed by two-way ANOVA (*<i>p <</i> 0.05; **<i>p <</i> 0.01; ***<i>p <</i> 0.001; NS, not significant) with post hoc Bonferroni correction to compare individual CCl₄ time points with respective vehicle controls (^#<i>p <</i> 0.05; ^##<i>p <</i> 0.01; ^###<i>p <</i> 0.001).</p