DRUG UTILIZATION PATTERN OF ANTIDIABETIC DRUGS AMONG DIABETIC OUTPATIENTS IN A TERTIARY CARE HOSPITAL

 Objective: The aim was to evaluate the drug utilization pattern of anti-diabetic drugs in diabetic outpatients and monitor the adverse drug reactions(ADRs) associated with anti-diabetic therapy.Methods: A prospective observational study was carried out in adult diabetic patients visiting the outpatient Departments of General Medicine andEndocrinology of a tertiary care hospital. Demographic data, drug utilization pattern and ADRs due to anti-diabetic drugs were summarized.Results: In the present study, 99 (50.3%) of the 197 diabetic patients were males. Majority of patients were in the age group of 51-60 years (39.6%) andmost of the patients (36.5%) had a diabetic history of <5 years. Metformin was the most commonly prescribed drug (68%), followed by sulfonylureaclass of drugs (49.7%). Nearly, 42% patients were using insulin preparations with 30.4% using biphasic isophane human insulin. Majority of thepatients (58.4%) were on multidrug therapy with two drug therapies being received by nearly 40%. Metformin was the most commonly prescribeddrug in monotherapy (18.8%) and glimepiride + metformin was the most common two drug therapy (13.2%). Co-morbid condition was found in 172patients (87.3%) with hypertension (68.5%) being the most common co-morbid condition. 17 ADRs were observed with hypoglycemia being the mostcommon ADR reported.Conclusions: Metformin was the most commonly used drug. The prescribing trend also appears to be moving towards combination therapyparticularly two drug therapies.Keywords: Drug utilization, Anti-diabetic drug, Adverse drug reaction

Review Article Oral contraceptives and oral health: an insight

ABSTRAC

The Role of Serum Interleukin-6 Levels in Prognosticating Postoperative Complications After Cytoreductive Surgery for Ovarian Cancers: A Prospective Observational Study

Background: Interleukin-6 (IL-6), a pro-inflammatory cytokine, has been associated with adverse prognosis in ovarian cancer. Cytoreductive surgery for ovarian cancer has a higher risk of postoperative surgical complications (POCs). We aimed to find out if serum IL-6 is elevated preoperatively in patients undergoing cytoreductive surgery for ovarian cancer and if it can predict POCs. We also compared its trend with serum C-reactive protein (CRP) in the early postoperative period. Materials and Methods: Fifty-one patients between 18–75 years, posted for elective ovarian cytoreductive surgery at a tertiary cancer hospital were included after taking informed consent. Serum IL-6 and CRP were done the day before surgery and repeated 24 and 72 hours post-surgery. All parameters that affect POCs were captured. POCs were graded using the Clavein Dindo classification. We recorded the length of the intensive care unit (ICU), hospital stay, and 30-day mortality. Appropriate statistical tests were used and p value <0.05 was considered significant. Results: Out of 51 enrolled patients, 46 were included for data analysis after exclusions. The mean age of patients in this study was 49.76 +/- 12.42 years with a mean surgical duration of 302.39 +/- 127.04 minutes and mean blood loss of 332.6 +/- 274.71 mL. The incidence of POCs in our study was 21.7% (10/46 patients). Preoperative IL-6 was raised and was able to predict POCs with 70% sensitivity and 86% specificity at a cutoff value of 23.56 pg./mL (R2 = 0.71; AUC = 0.79). In patients who developed POCs, IL-6 values (1196.7+/-1461.4 pg./mL) peaked at 24 hours whereas CRP values (360 +/- 430.1 mg/L) peaked at 72 hours; thus, allowing early prognostication with IL-6. The cut-off value of serum IL-6 at 24 hours to predict POCs is 480 pg./mL (R2 = 0.50; AUC = 0.79) with 80% sensitivity and 89% specificity. Two patients died - on postoperative days 5 and 28 respectively. Conclusion: Preoperative IL-6 is raised in patients with ovarian cancer posted for cytoreductive surgery. A cut-off value of 23.56 pg./mL preoperatively and 480 pg./mL at 24 hours after surgery could predict postoperative surgical complications

The antioxidant and antiproliferative activities of methanolic extracts from Njavara rice bran

<p>Abstract</p> <p>Background</p> <p>Free radical-induced oxidative stress is the root cause for many human diseases. Naturally occurring antioxidant supplements from plants are vital to counter the oxidative damage in cells. The main objective of the present study was to characterize the antioxidant and antiproliferative potential of rice bran extracted from an important Indian rice variety, Njavara and to compare the same with two commercially available basmati rice varieties: Vasumathi, Yamini and a non medicinal variety, Jyothi.</p> <p>Methods</p> <p>Methanolic extracts of rice bran from four varieties; Vasumathi, Yamini, Jyothi and Njavara were used to study their total phenolic and flavonoid contents, <it>in vitro </it>antioxidant activities including total antioxidant activity, scavenging of nitric oxide and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical, reducing power and cytotoxic activity in C6 glioma cells. Correlation coefficient and regression analysis were done by using Sigmastat version 3.1 and Stata statistical package respectively.</p> <p>Results</p> <p>Rice bran methanolic extract from Njavara showed the highest antioxidant and cell cytotoxic properties compared to the other three rice varieties. IC₅₀values for scavenging DPPH and nitric oxide were in the range of 30.85-87.72 μg/ml and 52.25-107.18 μg/ml respectively. Total antioxidant activity and reducing power were increased with increasing amounts of the extract. Total phenolic and flavonoid contents were in the range of 3.2-12.4 mg gallic acid-equivalent (GAE)/g bran and 1.68-8.5 mg quercetin-equivalent (QEE)/g bran respectively. IC₅₀values of cytotoxic assay (MTT assay) were 17.53-57.78 μg/ml. Correlation coefficient and regression analysis of phenolic content with DPPH and NO scavenging, MTT (-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay, total antioxidant assay and reducing power showed a highly significant correlation coefficient values (96-99%) and regression values (91-98%).</p> <p>Conclusion</p> <p>The results of the present study show that the crude methanolic extract from Njavara rice bran contains significantly high polyphenolic compounds with superior antioxidant activity as evidenced by scavenging of free radicals including DPPH and NO. Njavara extracts also showed highest reducing power activity, anti-proliferative property in C6 glioma cells. In conclusion, it is conceivable that the Njavara rice variety could be exploited as one of the potential sources for plant - based pharmaceutical products.</p

Purification and Characterization of a Sperm Motility Inhibiting Factor from Caprine Epididymal Plasma

Several studies have been reported on the occurrence of sperm motility inhibiting factors in the male reproductive fluids of different mammalian species, but these proteins have not been adequately purified and characterized. A novel sperm motility inhibiting factor (MIF-II) has been purified from caprine epididymal plasma (EP) by Hydroxylapatite gel adsorption chromatography, DEAE-Cellulose ion-exchange chromatography and chromatofocusing. The MIF-II has been purified to apparent homogeneity and the molecular weight estimated by Sephacryl S-300 gel filtration is 160 kDa. MIF-II is a dimeric protein, made up of two subunits each having a molecular mass of 80 kDa as shown by SDS-PAGE. The isoelectric point of MIF-II is 5.1 as determined by chromatofocusing and isoelectric focusing. It is a heat labile protein and maximal active at the pH 6.9 to 7.5. The sperm motility inhibiting protein factor at 2 µg/ml (12.5 nM) level showed maximal motility-inhibiting activity. The observation that the epididymal plasma factor lowered the intracellular cAMP level of spermatozoa in a concentration-dependent manner suggests that it may block the motility of caprine cauda spermatozoa by interfering the cAMP dependent motility function. The results revealed that the purified protein factor has the potential of sperm motility inhibition and may serve as a vaginal contraceptive. The antibody raised against the MIF-II has the potential for enhancement of forward motility of cauda-spermatozoa. This antibody may thus be useful for solving some of the problems of male infertility due to low sperm motility

Withaferin a-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species

Withaferin A (WA), a promising anticancer constituent of Ayurvedic medicinal plant Withania somnifera, inhibits growth of MDA-MB-231 and MCF-7 human breast cancer cells in culture and MDA-MB-231 xenografts in vivo in association with apoptosis induction, but the mechanism of cell death is not fully understood. We now demonstrate, for the first time, that WA-induced apoptosis is mediated by reactive oxygen species (ROS) production due to inhibition of mitochondrial respiration. WA treatment caused ROS production in MDA-MB-231 and MCF-7 cells, but not in a normal human mammary epithelial cell line (HMEC). The HMEC was also resistant to WA-induced apoptosis. WA-mediated ROS production as well as apoptotic histone-associated DNA fragment release into the cytosol was significantly attenuated by ectopic expression of Cu,Zn-superoxide dismutase in both MDA-MB-231 and MCF-7 cells. ROS production resulting from WA exposure was accompanied by inhibition of oxidative phosphorylation and inhibition of complex III activity. Mitochondrial DNA-deficient Rho-0 variants of MDA-MB-231 and MCF-7 cells were resistant to WA-induced ROS production, collapse of mitochondrial membrane potential, and apoptosis compared with respective wild-type cells. WA treatment resulted in activation of Bax and Bak in MDA-MB-231 and MCF-7 cells, and SV40 immortalized embryonic fibroblasts derived from Bax and Bak double knockout mouse were significantly more resistant to WA-induced apoptosis compared with fibroblasts derived from wild-type mouse. In conclusion, the present study provides novel insight into the molecular circuitry of WA-induced apoptosis involving ROS production and activation of Bax/Bak. © 2011 Hahm et al

Phyllanthus spp. Induces Selective Growth Inhibition of PC-3 and MeWo Human Cancer Cells through Modulation of Cell Cycle and Induction of Apoptosis

BACKGROUND: Phyllanthus is a traditional medicinal plant that has been used in the treatment of many diseases including hepatitis and diabetes. The main aim of the present work was to investigate the potential cytotoxic effects of aqueous and methanolic extracts of four Phyllanthus species (P.amarus, P.niruri, P.urinaria and P.watsonii) against skin melanoma and prostate cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: Phyllanthus plant appears to possess cytotoxic properties with half-maximal inhibitory concentration (IC(50)) values of 150-300 µg/ml for aqueous extract and 50-150 µg/ml for methanolic extract that were determined using the MTS reduction assay. In comparison, the plant extracts did not show any significant cytotoxicity on normal human skin (CCD-1127Sk) and prostate (RWPE-1) cells. The extracts appeared to act by causing the formation of a clear "ladder" fragmentation of apoptotic DNA on agarose gel, displayed TUNEL-positive cells with an elevation of caspase-3 and -7 activities. The Lactate Dehydrogenase (LDH) level was lower than 15% in Phyllanthus treated-cancer cells. These indicate that Phyllanthus extracts have the ability to induce apoptosis with minimal necrotic effects. Furthermore, cell cycle analysis revealed that Phyllanthus induced a Go/G1-phase arrest on PC-3 cells and a S-phase arrest on MeWo cells and these were accompanied by accumulation of cells in the Sub-G1 (apoptosis) phase. The cytotoxic properties may be due to the presence of polyphenol compounds such as ellagitannins, gallotannins, flavonoids and phenolic acids found both in the water and methanol extract of the plants. CONCLUSIONS/SIGNIFICANCE: Phyllanthus plant exerts its growth inhibition effect in a selective manner towards cancer cells through the modulation of cell cycle and induction of apoptosis via caspases activation in melanoma and prostate cancer cells. Hence, Phyllanthus may be sourced for the development of a potent apoptosis-inducing anticancer agent