Expanding horizons in the treatment of mantle cell lymphoma: Ibrutinib a novel BTK-targeting inhibitor

Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma characterized by involvement of the lymph nodes, spleen, blood, and bone marrow with short remission duration to standard therapies and a median overall survival of 4–5 years. Small molecule inhibitors targeting dysregulated pathways (MAPK/ERK, PI3K/PKB/mTOR, JAK/STAT) have significantly improved clinical outcomes in cancer patients. Recently Bruton’s tyrosine kinase (BTK), a crucial terminal kinase enzyme in the B-cell antigen receptor (BCR) signaling pathway, has emerged as an attractive target for therapeutic intervention in human malignancies and autoimmune disorders. Ibrutinib, a novel first-in-human BTK-inhibitor, has demonstrated clinical effectiveness and tolerability in clinical trials, recently been approved by FDA in the treatment of MCL.

Dapagliflozin: a new adjunct in the treatment of Type 2 diabetes mellitus

Diabetes mellitus (DM) Type 2 is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. The classic symptoms are excess thirst, frequent urination, and constant hunger. Management of Type 2 diabetes focuses on lifestyle interventions, lowering other cardiovascular risk factors, and maintaining blood glucose levels in the normal range. There are several classes of anti-diabetic medications available and these include sulfonylureas, nonsulfonylurea secretagogues, alpha glucosidase inhibitors, thiazolidinediones, glucagon-like peptide-1 analog, and dipeptidyl peptidase-4 inhibitors. Recently, dapagliflozin (Farxiga™), a sodium-glucose cotransporter 2 inhibitor has been approved by Food and Drug Administration as an adjunct to diet and exercises to improve glycemic control in adults with Type 2 DM

International Journal of Pharma and Bio Sciences RESEARCH ARTICLE BIO CHEMISTRY RELATIONSHIP OF TESTOSTERONE LEVELS IN MALES WITH CORONARY HEART

Males are more than twice at the risk of dying from coronary disease than women. The finding that estrogen has a protective role in females led to the speculation that testosterone is deleterious to the male cardiovascular system and contributes to the vascular risk, but subsequent research showed little evidence that endogenous testosterone is an adverse risk factor, but the role of testosterone status and replacement therapy on male health is controversial. We studied the levels of testosterone in 60 males with recent coronary heart disease confirmed by the levels of troponin I ultra and compared them with the age matched controls from normal population. These parameters were assayed using chemiluminescent technology. We found that in males with CHD the testosterone levels were significantly reduced. This article discusses the cardioprotective role of testosterone in males. This article can be downloaded from www.ijpbs.net B- 566KEYWORD

Hepatoprotective effect of trimethylgallic acid esters against carbon tetrachloride-induced liver injury in rats

803-809Gallic acid and its derivatives are potential therapeutic agents for treating various oxidative stress mediated disorders. In the present study, we investigated the hepatoprotective effects of newly synthesized conjugated trimethylgallic acid (TMGA) esters against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Animals were pre-treated with TMGA esters at their respective doses for 7 days against CCl4-induced hepatotoxicity. The histopathological changes were evaluated to find out degenerative fatty changes including vacuole formation, inflammation and tissue necrosis. Various biomarkers of oxidative stress (lipid peroxidation, glutathione levels, and endogenous antioxidant enzyme activities), liver enzymes (AST and ALT), triacylglycerol and cholesterol were evaluated. Pre-treatment with TMGA esters (MRG, MGG, MSG, and MUG at the dose of 28.71, 30.03, 31.35, 33.62 mg/kg/day), respectively reversed the CCl4-induced liver injury scores (reduced vacuole formation, inflammation and necrosis), biochemical parameters of plasma (increased AST, ALT, TG, and cholesterol), antioxidant enzymes (increased lipid peroxidation and nitrite levels; decreased glutathione levels, superoxide dismutase and catalase activities) in liver tissues and inflammatory surge (serum TNF-α) significantly. The study revealed that TMGA esters exerted hepatoprotective effects in CCl4-induced rats, specifically by modulating oxidative-nitrosative stress and inflammation

Alarming levels of drug-resistant tuberculosis in HIV-infected patients in metropolitan Mumbai, India.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. METHODS: A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. RESULTS: Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%-40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. CONCLUSION: The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and health facilities. These data highlight the need to promptly diagnose drug-resistance among all HIV-infected patients by systematically offering access to first and second-line DST to all patients with 'presumptive TB' rather than 'presumptive DR-TB' and tailor the treatment regimen based on the resistance patterns

Demographic and clinical factors associated with multidrug-resistant tuberculosis in HIV-infected tuberculosis patients, Mumbai, India.

<p>ART: Antiretroviral treatment, CI; Confidence Intervals ⁺Patients with recorded family income, N = 140* Patients with available information about CD4 count, last visit N = 164** Patients on ART with available information about ART initiation date, N = 126^aaOR; adjusted Odds ratios (calculated by binary logistic regression using multiple imputation for CD4 missing data).</p><p>Demographic and clinical factors associated with multidrug-resistant tuberculosis in HIV-infected tuberculosis patients, Mumbai, India.</p

Drug-resistant tuberculosis among HIV-infected patients with presumptive tuberculosis, Mumbai, India.

<p>Drug-resistant tuberculosis among HIV-infected patients with presumptive tuberculosis, Mumbai, India.</p

Demographic and clinical factors associated with drug-resistant tuberculosis in HIV-infected tuberculosis patients, Mumbai, India.

<p>ART: Antiretroviral treatment, CI; Confidence Intervals ⁺Patients with recorded family income, N = 162* Patients with available information about CD4 count, last visit N = 185** Patients on ART with available information about ART initiation date, N = 126^a aOR; adjusted Odds ratios (calculated by binary logistic regression using multiple imputation for CD4 missing data).</p><p>Demographic and clinical factors associated with drug-resistant tuberculosis in HIV-infected tuberculosis patients, Mumbai, India.</p

Demographic and clinical characteristics of HIV-infected patients with presumptive TB, Mumbai, India.

<p>ART: Antiretroviral treatment* Patients on ART with available information about ART initiation date, N = 1370.</p><p>Demographic and clinical characteristics of HIV-infected patients with presumptive TB, Mumbai, India.</p

Demographic and clinical factors associated with culture-positive tuberculosis in HIV-infected patients, Mumbai, India.

<p>ART: Antiretroviral treatment, IQR: Inter-quartile range, CI; Confidence Intervals ⁺Patients with recorded family income, N = 1452* Patients with available information on CD4, last visit, N = 1582** Patients on ART with available information about ART initiation date, N = 1370^a aPR; adjusted Prevalence Ratios (calculated by Poisson regression using multiple imputation for CD4 missing data).</p><p>Demographic and clinical factors associated with culture-positive tuberculosis in HIV-infected patients, Mumbai, India.</p