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The toxicity induced by 7, 12-dimethylbenz(α)anthracene (DMBA) has been widely delineated by a number of researchers. This potent chemical damages many internal organs including liver, by inducing the production of reactive oxygen species, DNA-adduct formation and affecting the activities of phase I, II, antioxidant and serum enzymes. Glucosinolate hydrolytic products like isothiocyanates (ITCs) are well known for inhibiting the DNA-adduct formation and modulating phase I, II enzymes. Sulforaphane is ITC, currently under phase trials, is readily metabolized and inter-converted into erucin upon ingestion. We isolated erucin from Eruca sativa (Mill.) Thell. evaluated its hepatoprotective role in DMBA induced toxicity in male wistar rats. The rats were subjected to hepatic damage by five day regular intraperitoneal doses of DMBA. At the end of the protocol, the rats were euthanized, their blood was collected and livers were processed. The liver homogenate was analyzed for phase I (NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, cytochrome P450, cytochrome P420 and cytochrome b5), phase II (DT diaphorase, glutathione-S-transferase and γ-glutamyl transpeptidase) and antioxidant enzymes (superoxide dismutase, catalase, guaiacol peroxidise, ascorbate peroxidise, glutathione reductase and lactate dehydrogenase). The level of thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes and reduced glutathione in the liver homogenate was also analyzed. The serum was also analyzed for markers indicating hepatic damage (alkaline phosphatase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, direct bilirubin and total bilirubin). Erucin provided significant protection against DMBA induced damage by modulating the phase I, II and antioxidant enzymes. The histological evaluation of liver tissue was also conducted, which showed the hepatoprotective role of erucin.

The present study envisages the cytotoxic potential of 3-butenyl isothiocyanate isolated from Brassica juncea L. Czern var. Pusa Jaikisan against the human cancer cell lines viz. prostate, bone osteosarcoma, cervical, liver, neuroblastoma and breast cancer. As the compound was observed to be more effective against prostate cancer cell line, therefore, this cell line was further used to study the mechanism of cell death using neutral red assay, reactive oxygen species assay, mitochondrial membrane potential assay, microscopic and cell cycle analysis. The mechanistic analysis indicated that it induced the cell death of prostate cancer cells via apoptosis and hence made it an excellent choice as an effective anticancer compound.

Lamivudine-resistant hepatitis B virus (HBV) is found in about 15–32% of infected patients with or without co-infection with HIV-1 after 1 year of lamivudine therapy. Adefovir dipivoxil is active in vivo and in vitro against wild-type and lamivudine-resistant HBV. We assessed the safety and efficacy of a once daily dose of adefovir dipivoxil in an openlabel trial for the treatment of lamivudine-resistant HBV infection in HIV-1-infected patients. 35 HIV-1/HBV co-infected patients receiving lamivudine therapy (150 mg twice daily) as part of their current HIV-1 antiretroviral regimen were enrolled. Patients received a 10 mg once-daily dose of adefovir dipivoxil for 48 weeks while maintaining their existing anti-HIV-1 therapy, including lamivudine. Patients were assessed every 4 weeks for safety and efficacy. Four patients withdrew from the study (two because of adverse events), leaving 31 patients who received adefovir dipivoxil for a median of 48 weeks (range 44–48). Mean decreases in serum HBV DNA concentrations from baseline (log 8·64 copies/mL [SE log 0·08]) were -log 3·40 copies/mL [log 0·12] at week 24 (n=31) and -log 4·01 copies/mL [log 0·17] at week 48 (n=29; p<0·0001). Two patients underwent hepatitis B e antigen seroconversion—one at week 32 and one at week 36. Adefovir dipivoxil was generally well tolerated, but was associated with a transient increase in serum alanine aminotransferase concentrations in 15 patients. We found no significant changes in either HIV-1 RNA or CD4 cell count. These results indicate that 48 weeks of 10 mg daily adefovir dipivoxil is well tolerated and active against lamivudine-resistant HBV in HIV-1/HBV co-infected patients.

Alagille syndrome is a rare genetic disease that often presents with severe cholestasis and pruritus. There are no approved drugs for management. Maralixibat, an apical, sodium-dependent, bile acid transport inhibitor, prevents enterohepatic bile acid recirculation. We evaluated the safety and efficacy of maralixibat for children with cholestasis in Alagille syndrome. ICONIC was a placebo-controlled, randomised withdrawal period (RWD), phase 2b study with open-label extension in children (aged 1–18 years) with Alagille syndrome (NCT02160782). Eligible participants had more than three times the normal serum bile acid (sBA) levels and intractable pruritus. After 18 weeks of maralixibat 380 μg/kg once per day, participants were randomly assigned (1:1) to continue maralixibat or receive placebo for 4 weeks. Subsequently, all participants received open-label maralixibat until week 48. During the long-term extension (204 weeks reported), doses were increased up to 380 μg/kg twice per day. The primary endpoint was the mean sBA change during the RWD in participants with at least 50% sBA reduction by week 18. Cholestastic pruritus was assessed using observer-rated, patient-rated, and clinician-rated 0–4 scales. The safety population was defined as all participants who had received at least one dose of maralixibat. This trial was registered with ClinicalTrials.gov, NCT02160782, and is closed to recruitment. Between Oct 28, 2014, and Aug 14, 2015, 31 participants (mean age 5·4 years [SD 4·25]) were enrolled and 28 analysed at week 48. Of the 29 participants who entered the randomised drug withdrawal period, ten (34%) were female and 19 (66%) were male. In the RWD, participants switched to placebo had significant increases in sBA (94 μmol/L, 95% CI 23 to 164) and pruritus (1·7 points, 95% CI 1·2 to 2·2), whereas participants who continued maralixibat maintained treatment effect. This study met the primary endpoint (least square mean difference –117 μmol/L, 95% CI –232 to –2). From baseline to week 48, sBA (–96 μmol/L, –162 to –31) and pruritus (–1·6 pts, –2·1 to –1·1) improved. In participants who continued to week 204 (n=15) all improvements were maintained. Maralixibat was generally safe and well tolerated throughout. The most frequent adverse events were gastrointestinal related. Most adverse events were self-limiting in nature and mild-to-moderate in severity. In children with Alagille syndrome, maralixibat is, to our knowledge, the first agent to show durable and clinically meaningful improvements in cholestasis. Maralixibat might represent a new treatment paradigm for chronic cholestasis in Alagille syndrome. Mirum Pharmaceuticals.

Background: Vermicompost (VC) made from cattle dung as raw material was used as soil supplement in the plots of size 4.5 x 4.5 m. Five treatments were given viz. Soil (control), VC@5 t/ha, VC@10 t/ha, VC@20 t/ha and NPK (recommended by PAU, Ludhiana) in triplicates in a Randomized Block Design (RBD). A total of 50 plants were selected randomly for the assessment of growth and yield of wheat Triticum aestivum L.. Results: Most of the growth, yield and quality parameters were found to be maximum in NPK treatment. All the growth, yield and quality parameters in vermicompost treatments varied significantly from control though differences within various vermicompost treatments were not found to be significant. Conclusion: It has been observed that there is no significant difference on applying higher doses of vermicompost and lowest dose (5 t/ha) is as effective as higher doses. So, vermicompost application is cost effective.

The toxicity induced by 7, 12-dimethylbenz([alpha])anthracene (DMBA) has been widely delineated by a number of researchers. This potent chemical damages many internal organs including liver, by inducing the production of reactive oxygen species, DNA-adduct formation and affecting the activities of phase I, II, antioxidant and serum enzymes. Glucosinolate hydrolytic products like isothiocyanates (ITCs) are well known for inhibiting the DNA-adduct formation and modulating phase I, II enzymes. Sulforaphane is ITC, currently under phase trials, is readily metabolized and inter-converted into erucin upon ingestion. We isolated erucin from Eruca sativa (Mill.) Thell. evaluated its hepatoprotective role in DMBA induced toxicity in male wistar rats. The rats were subjected to hepatic damage by five day regular intraperitoneal doses of DMBA. At the end of the protocol, the rats were euthanized, their blood was collected and livers were processed. The liver homogenate was analyzed for phase I (NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, cytochrome P450, cytochrome P420 and cytochrome b5), phase II (DT diaphorase, glutathione-S-transferase and [gamma]-glutamyl transpeptidase) and antioxidant enzymes (superoxide dismutase, catalase, guaiacol peroxidise, ascorbate peroxidise, glutathione reductase and lactate dehydrogenase). The level of thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes and reduced glutathione in the liver homogenate was also analyzed. The serum was also analyzed for markers indicating hepatic damage (alkaline phosphatase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, direct bilirubin and total bilirubin). Erucin provided significant protection against DMBA induced damage by modulating the phase I, II and antioxidant enzymes. The histological evaluation of liver tissue was also conducted, which showed the hepatoprotective role of erucin.

We collected human immunodeficiency virus (HIV) disease progression, survival, most recent CD4 cell count, and plasma HIV RNA levels from patients (n = 157) who participated in randomized clinical trials of interleukin (IL)–2 that commenced before 1995. Data were available for 155 (99%) patients. Statistical analyses were based on the intention-to-treat principle. Median follow-up was 28 months and 30 months for control and IL-2 patients, respectively. Twenty-five (16%) patients developed AIDS or died during follow-up (16 control patients vs. 9 IL-2 patients; R2 = 0.57; P = .22). Mean change from baseline CD4 cell count was significantly higher in patients randomized to receive IL-2 (368 vs. 153 cells/µL; P = .003). Mean change from baseline plasma HIV RNA was significantly lower in patients randomized to receive IL-2 (−0.98 vs. −0.63 log copies/mL; P = .004). Significant improvements in CD4 cell count and plasma HIV RNA in recipients of IL-2 relative to control patients were associated with a nonsignificant trend toward improved clinical outcome.

Maralixibat (MRX) is an ileal bile acid transporter inhibitor (IBATi) recently approved by the Food and Drug Administration for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) 1 year of age and older. Recent data suggest that MRX is associated with improved event-free survival in this population suggesting that the drug may potentially improve liver disease outcomes beyond pruritus control in ALGS. Patients with ALGS clearly have impaired growth and therefore we evaluated the impact of long-term MRX treatment on the nutritional status of these patients.Height and weight Z-scores were evaluated in patients who participated in 3 clinical trials of MRX and their long-term, open-label extensions for treatment of cholestatic pruritus in ALGS; only patients for whom we had height and weight data at baseline and week 204 follow-up were included. T-tests and Pearson correlation coefficients were used to evaluate the association between height with other parameters known to correlate with growth.Data were available for 34 patients with baseline mean (SD) age of 6.7 (3.8) years, height Z-score of -1.66 (1.17) and weight Z-score of -1.46 (0.95). Overall, mean height Z-score increased to -1.29 (1.03) at week 204 (change from baseline: 0.37; p=0.0004). The greatest catch-up height gain was observed among those within the lowest baseline quartile height Z-scores, increasing from -3.1 (0.71) at baseline to -2.38 (0.82) at week 204 (change from baseline: 0.72; p=0.018), and there was a significant correlation between change in height and baseline height (r=-0.48; p=0.004). Similarly, greater catch-up weight gain was observed with lower baseline weight Z-scores, with a significant correlation between change in weight and baseline weight (r=-0.39; p=0.02). The change in height Z-scores correlated with the change in weight Z-scores such that greater catch-up linear growth was observed in patients with greater catch-up weight gain (r=0.73; p<0.0001). There was no clear change in vitamin D levels or albumin throughout treatment. Among patients with sBA <200 µmol/L at week 48, height Z-score increased from -1.58 (1.23) at baseline to -1.16 (1.00) at week 204 (change from baseline: 0.42; p=0.001), whereas there was no significant change in height Z-score among patients with sBA ≥200 µmol/L.Catch-up height and weight are observed in patients with ALGS treated with MRX, and importantly patients with the greatest height disadvantage at baseline had the greatest catch-up in height. Increased catch-up height was also seen in patients that achieved lower sBA with MRX, suggesting an improvement in bile acid homeostasis may be a factor. Further analyses are needed comparing growth trajectories in MRX-treated patients to a natural history cohort of patients with ALGS to fully understand the attributability of MRX.