Patient based factors influencing drug compliance among hypertensive patients in a tertiary care hospital in Mysore

Background: Hypertension is deemed as the tip of the iceberg due to the mortality and morbidity associated with it. A major factor accounting for inadequate treatment of hypertension is poor compliance.Methods: Morisky 8-Item Medication Adherence Questionnaire was used for a cross sectional study. The term compliance is defined as the extent to which the patient’s behaviour coincides with the clinical prescription, implying that the patient defaults by not following the advice of the health care providerResults: Mean age of the participants was 59.2yrs (S.D. 10.37 yrs). Compliance was found to be good 71.3% of respondents, medium in 20.4% and poor in 8.3%.52.8% had one or two other ailments (diabetes, asthma etc.).Conclusions: Patient’s medication compliance is a multifactor behaviour in which the role of patient’s attitude is very important. Patients related factors known to affect compliance were equally distributed among good, medium and poorly compliant participant

Development of Mucoadhesive Nanoparticulate System of Ebastine for Nasal Drug Delivery

Purpose: To prepare and evaluate mucoadhesive nanoparticulate system of ebastine for nasal drug delivery.Methods: The nanoparticles were prepared by ionic gelation method using drug-chitosan weight ratios 1:1, 1:2 and 1:3, and incorporating 0.5 or 0.7 % w/v sodium tripolyphosphate (STPP) and poloxamer 407. The mucoadhesive nanoparticles were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), differential scanning colorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) and evaluated for drug loading, entrapment efficiency, in vitro mucoadhesion, in vitro drug release and ex-vivo permeation.Results: FTIR and DSC studies indicate that no chemical interaction occurred between the drug and polymer. Nanoparticle size ranged from 169 to 500 nm. Drug loading and entrapment efficiency increased with increase in chitosan concentration and decreased with increase in poloxamer 407 concentration. The highest drug loading obtained for the nanoparticles was 19.5 %. With increase in polymer (chitosan) concentration (1:1 to 1:3), production yield was unchanged (73.2 to 74.4 % (F6)). Mucoadhesion increased with increase in the concentration of chitosan. In vitro drug release from all the formulations was biphasic, being characterized by a slight ‘burst’ followed by slow release. At the end of 8 h F6 (1:3) showed drug release of only 86.9 %, indicating sustained release. Ex-vivo permeation of pure ebastine was more rapid than from F6, thus indicating the capability of chitosan to control drug permeation rate through sheep nasal mucosa.Conclusion: The results indicate that a mucoadhesive nanoparticulate system can be used effectively for the nasal delivery of the antihistamine, ebastine.Keywords: Chitosan, Ebastine, Mucoadhesive, Nanoparticles, Ionotropic gelation, Permeation, Drug release, Poloxame

Policy of foreign direct investment liberalisation in India: implications for retail sector

This study has analysed the impact of liberalisation of Indian economy and FDI policy on the retail sector since its implementation in the 1990s. It also further analyses sub-categories by investigating its impact on the unorganised retail sector and the flow of FDI in single-brand retail and multi-brand retail sectors. A comprehensive and critical review of the existing evidence on the subject was carried out, and descriptive statistical analysis of data from 1991 to 2013 was performed which leads to conclude that the policy of FDI liberalisation has proved to provide diversification and sustainable development to the Indian economy and specifically retail sector which is considered to be one of the significant pillars of economy. Furthermore, for continuous growth of the economy, it seems vital to encourage more investment in other sectors by liberalising the restrictive policies

Aldose reductase deficiency in mice protects from ragweed pollen extract (RWE)-induced allergic asthma

<p>Abstract</p> <p>Background</p> <p>Childhood hospitalization related to asthma remains at historically high levels, and its incidence is on the rise world-wide. Previously, we have demonstrated that aldose reductase (AR), a regulatory enzyme of polyol pathway, is a major mediator of allergen-induced asthma pathogenesis in mouse models. Here, using AR null (AR^-/-) mice we have investigated the effect of AR deficiency on the pathogenesis of ragweed pollen extract (RWE)-induced allergic asthma in mice and also examined the efficacy of enteral administration of highly specific AR inhibitor, fidarestat.</p> <p>Methods</p> <p>The wild type (WT) and AR^-/-mice were sensitized and challenged with RWE to induce allergic asthma. AR inhibitor, fidarestat was administered orally. Airway hyper-responsiveness was measured in unrestrained animals using whole body plethysmography. Mucin levels and Th2 cytokine in broncho-alveolar lavage (BAL) were determined using mouse anti-Muc5A/C ELISA kit and multiplex cytokine array, respectively. Eosinophils infiltration and goblet cells were assessed by H&E and periodic acid Schiff (PAS)-staining of formalin-fixed, paraffin-embedded lung sections. T regulatory cells were assessed in spleen derived CD4⁺CD25⁺T cells population.</p> <p>Results</p> <p>Deficiency of AR in mice led to significantly decreased PENH, a marker of airway hyper-responsiveness, metaplasia of airway epithelial cells and mucus hyper-secretion following RWE-challenge. This was accompanied by a dramatic decrease in infiltration of eosinophils into sub-epithelium of lung as well as in BAL and release of Th2 cytokines in response to RWE-challenge of AR^-/-mice. Further, enteral administration of fidarestat significantly prevented eosinophils infiltration, airway hyper-responsiveness and also markedly increased population of T regulatory (CD4⁺CD25⁺FoxP3⁺) cells as compared to RWE-sensitized and challenged mice not treated with fidarestat.</p> <p>Conclusion</p> <p>Our results using AR^-/-mice strongly suggest the role of AR in allergic asthma pathogenesis and effectiveness of oral administration of AR inhibitor in RWE-induced asthma in mice supports the use of AR inhibitors in the treatment of allergic asthma.</p

Impact of a probiotic fermented milk in the gut ecosystem and in the systemic immunity using a non-severe protein-energy-malnutrition model in mice

<p>Abstract</p> <p>Background</p> <p>Malnutrition affects the immune response, causing a decrease of defence mechanisms and making the host more susceptible to infections. Probiotics can reconstitute the intestinal mucosa and stimulate local and systemic immunity. The aim of this work was evaluate the effects of a probiotic fermented milk as a complement of a re-nutrition diet, on the recovery of the intestinal barrier, and mucosal and systemic immune functions in a murine model of non-severe protein-energy-malnutrition. Its potential protection against <it>Salmonella enterica </it>serovar Typhimurium (<it>S</it>. Typhimurium) infection was also analyzed.</p> <p>Methods</p> <p>Mice were undernourished and divided into 3 groups according to the dietary supplement received during re-nutrition (milk, probiotic fermented milk or its bacterial free supernatant) and compared to well-nourished and malnourished mice. They were sacrificed previous to the re-nutrition and 5 days post re-nutrition. The phagocytic activity of macrophages from spleen and peritoneum and the changes in the intestinal histology and microbiota were evaluated. Different immune cell populations and cytokine productions were analyzed in the small intestine tissues. The effect of the re-nutrition supplements on the systemic immunity using OVA antigen and against an infection with <it>S. </it>Typhimurium was also studied.</p> <p>Results</p> <p>Probiotic fermented milk was the most effective re-nutrition diet that improved the intestinal microbiota. Its administration also increased the number of IgA+ cells, macrophages and dendritic cells. The production of different cytokine (IFN-γ, TNF-α, IL-12) by these cells and the phagocytic activity in peritoneum and spleen was also increased. This re-nutrition diet also stimulated the systemic immune response against OVA antigen which was diminished after the malnutrition period and also improved the host response against <it>S. </it>Typhimurium, decreasing the spread of pathogenic bacteria to the liver and the spleen. The importance of the metabolites released during milk fermentation was also demonstrated through the analysis of the bacterial free supernatant obtained from the probiotic fermented milk, but the whole product showed the best effects in the parameters evaluated in this study.</p> <p>Conclusions</p> <p>The administration of probiotic fermented milk as a dietary supplement during the re-nutrition process in a murine immunodeficiency model by malnutrition could be a good adjuvant diet to improve the gut and systemic immune response for the protection against <it>Salmonella </it>infection.</p

Dysregulation of MicroRNA-34a Expression in Head and Neck Squamous Cell Carcinoma Promotes Tumor Growth and Tumor Angiogenesis

MicroRNAs (miRs) are small non-coding RNAs that play an important role in cancer development where they can act as oncogenes or as tumor-suppressors. miR-34a is a tumor-suppressor that is frequently downregulated in a number of tumor types. However, little is known about the role of miR-34a in head and neck squamous cell carcinoma (HNSCC).miR-34a expression in tumor samples, HNSCC cell lines and endothelial cells was examined by real time PCR. Lipofectamine-2000 was used to transfect miR-34a in HNSCC cell lines and human endothelial cells. Cell-proliferation, migration and clonogenic survival was examined by MTT, Xcelligence system, scratch assay and colony formation assay. miR-34a effect on tumor growth and tumor angiogenesis was examined by in vivo SCID mouse xenograft model. Our results demonstrate that miR-34a is significantly downregulated in HNSCC tumors and cell lines. Ectopic expression of miR-34a in HNSCC cell lines significantly inhibited tumor cell proliferation, colony formation and migration. miR-34a overexpression also markedly downregulated E2F3 and survivin levels. Rescue experiments using microRNA resistant E2F3 isoforms suggest that miR-34a-mediated inhibition of cell proliferation and colony formation is predominantly mediated by E2F3a isoform. In addition, tumor samples from HNSCC patients showed an inverse relationship between miR-34a and survivin as well as miR-34a and E2F3 levels. Overexpression of E2F3a completely rescued survivin expression in miR-34a expressing cells, thereby suggesting that miR-34a may be regulating survivin expression via E2F3a. Ectopic expression of miR-34a also significantly inhibited tumor growth and tumor angiogenesis in a SCID mouse xenograft model. Interestingly, miR-34a inhibited tumor angiogenesis by blocking VEGF production by tumor cells as well as directly inhibiting endothelial cell functions.Taken together, these findings suggest that dysregulation of miR-34a expression is common in HNSCC and modulation of miR34a activity might represent a novel therapeutic strategy for the treatment of HNSCC

Carotid Artery Stenting Using a Novel Self-Expanding Braided Nickel–Titanium Stent: Feasibility and Safety Porcine Trial

We studied the deliverability and safety of a braided, self-expanding, closed-cell nickel–titanium (NiTi) stent (E-volution, Jotec GmbH, Hechingen, Germany) especially designed for the endovascular treatment of carotid artery bifurcation stenosis with special regard to in-stent stenosis and thrombosis compared with a laser-cut reference nitinol stent in a porcine model of percutaneous vascular interventions. We aimed to assess histopathologic response in minipig carotid and subclavian arteries. Eight minipigs received a total of 42 stents: 14 reference stents and 28 E-volution stents. Eleven of the E-volution stents were additionally coated with heparin. Control angiography was obtained immediately before and after vascular intervention as well as 4 weeks after the procedure. Primary endpoints were 28 days of angiographic analyses as well as histomorphometric analysis, including injury score, inflammation score, luminal diameter, vessel diameter, maximal neointimal thickness, and area of in-stent stenosis. Secondary end points were procedural success, 28-day mortality, and stent thrombosis. All stents could be delivered successfully without procedural complications, morbidity, or mortality during our observation time. As confirmed by histology, no in-stent thrombosis was observed. Compared with common carotid arteries, subclavian arteries are significantly more vulnerable to developing in-stent stenosis caused by neointima proliferation (p < 0.05). Compared with the use of 1 single stent/artery, serial application of two stents leads to a more excessive but not significantly different neointimal proliferation (p > 0.05). The E-volution stent, especially when heparin coated, is in line with the comparison to the laser-cut reference stent displaying similar results of angiographic, histologic, and histomorphometric analyses (p > 0.05). Compared with the reference laser-cut stent, the self-expanding nitinol stent (E-volution) with its advanced braiding technology is feasible and safe. In our opinion, the high radial resistive force and the advanced braided design with tight stent-strut interstices may be beneficial in terms of plaque stabilization. Further studies are necessary and warranted

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation