Safety profile of imatinib in Indian chronic myeloid leukemia patients

Introduction: Imatinib mesylate has become the choice of drug in the treatment of chronic myeloid leukemia. Objective: To study safety profile of Imatinib (specific inhibitor or bcrabl tryosne kinase protein) in Philadelphia chromosome t {(9:22), bcr-abl} positive chronic myeloid leukemia (CML) chronic phase patients. Materials and Methods: After IEC clearance, 36, BCR-ABL positive CML patients in the chronic phase of the disease were recruited. Imatinib mesylate (Gleevec, Novartis), was started (400mg daily) and followed up weekly in first month, two weekly till three months & monthly thereafter. Safety profile data, recorded in pre-designed proforma, were analyzed for time of onset, duration and severity of adverse effects. Causality relationship of recorded adverse events was established with imatinib therapy using WHO-UMC criteria. Results: A total of 222 adverse events were reported in 36 CML-CP patients over 12 months of follow up. Thrombocytopenia was the most commonly reported in 60% of the patients followed by musculoskeletal (17%), dermatological (16%), gastrointestinal disturbances (13%), body weight changes (11%), superficial edema (8%) and liver enzyme rise (4%). More than 80% events reported within months of therapy which persisted for less than 3 months in most of the cases. No treatment was needed in 68% of cases while therapy alteration was not needed in 88% of cases. Most of the reactions (60%) had probable relationship with the therapy. Conclusion: Imatinib was well tolerated, having only mild to moderate grade of toxicities, mostly within 3 months of therapy and most of them persisted for less than 3 months of duration, requiring only symptomatic treatment and drug withhold or dose decrement in only few cases

The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

Abstract Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART) when co-administered with rifampicin-containing antituberculosis treatment (ATT) and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1%) patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD) Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10), 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08), 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10) respectively and 3.04 μg/ml (in cases). Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in antiretroviral effectiveness. Larger sample sized studies and longer follow-up are required to identify populations of individuals where the reduction in nevirapine concentration may result in lower ART response or shorter response duration

Transconjunctival penetration of mitomycin C

<b>Aims:</b> The study was performed to estimate transconjunctival penetration of mitomycin C (MMC) to Tenon&#x2032;s tissue following application over the intact conjunctiva before routine trabeculectomy. <b> Settings and Design:</b> Institution-based case series. <b> Materials and Methods:</b> In 41 eyes of 41 patients, MMC (0.4 mg/ml for 3 min) was applied over the intact conjunctiva before beginning trabeculectomy. Tenon&#x2032;s capsule directly beneath the site of application was excised during trabeculectomy and was homogenized, centrifuged and MMC concentrations were analyzed using high-performance liquid chromatography (HPLC). <b> Statistical Analysis Used:</b> Statistical analysis was performed using stata0 8.0 version software (STATA Corporation, Houston, TX, USA). In this study, <i> P</i> -values less than 0.05 were considered as statistically significant. <b> Results:</b> The average weight of the sample of Tenon&#x2032;s tissue excised was 5.51 &#x00B1; 4.42 mg (range: 0.9-17.1) and the average estimated MMC concentration found to be present in Tenon&#x2032;s tissue using HPLC was 18.67 &#x00B1; 32.36 x 10^&#8722;6 moles/kg of the tissue (range: 0.38-197.05 x 10^&#8722;6 ). In 36 of the 41 patients (87.80&#x0025;), the MMC concentration reached above 2 x 10^&#8722;6 moles/kg of the tissue concentration required to inhibit human conjunctival fibroblasts. <b> Conclusions:</b> Mitomycin C does permeate into the subconjunctival tissue after supraconjunctival application for 3 min. Application of MMC over the conjunctiva may be a useful alternative to subconjunctival or subscleral application during routine trabeculectomy and as an adjunct for failing blebs

Antiproliferative activity of marine stingray Dasyatis sephenvenom on human cervical carcinoma cell line

AbstractBackgroundVenoms comprise mixtures of numerous bioactive compounds that have a wide range of pharmacologic actions. Toxins from venomous animals have attracted the attention of researchers because of their affinity for primary sites responsible for lethality and their efficacy at extremely low concentrations. The venoms of marine stingrays have not been extensively studied and limited data is available on them. The present study aims to evaluate the antiproliferative and biochemical properties of the venom obtained from a species of marine stingray (Dasyatis sephen) on human cervical cancer cell line HeLa.MethodsThe antiproliferative effect of D. sephen venom was determined by MTT assay, and the oxidative stress was determined by lipid peroxidation method along with assessment of changes in the enzymatic and non-enzymatic antioxidant status. We observed intracellular reactive oxygen species (ROS) levels by DCFH-DA method, mitochondrial membrane potential alterations by rhodamine 123 staining and apoptotic morphological changes by acridine orange/ethidium bromide dual staining method.ResultsD. sephen venom enhances lipid peroxidative markers such as thiobarbituric acid reactive substance, conjugated diene, and lipid hydroperoxide in HeLa cell lines. Stingray venom enhances the ROS levels, which is evidenced by the increased 2–7-diacetyl dichlorofluorescein fluorescence. Further, D. sephen venom treatment altered the mitochondrial membrane potential in HeLa cells. Additionally, we observed increased apoptotic morphological changes in D. sephen venom-treated groups. ConclusionsDasyatis sephen venom exhibits potent antiproliferative effect on HeLa cell line and upon further purification it could be a promising antiproliferative agent