DOXORUBICIN INDUCED COGNITION IMPAIRMENT IN RAT MODEL

 Objective: Doxorubicin (DOX) is a chemotherapeutic agent commonly used to treat a variety of cancers despite having well documented adverse sideeffects in organs like heart, liver, and kidney. The damage caused to brain, if any, and to what extent is, however, still not clear and the present studywas undertaken to estimate the possible role of DOX inducing cognitive impairment in Wistar rats.Methods: The study carried out in two groups of Wistar rats (n=6) with one group receiving DOX, and the other only normal saline used as control.During and after the experimentation period cognitive level of each rat was measured using Barnes maze (BM) till 8 weeks. At the end of theobservation period (after 8th week), a series of biochemical and histopathological studies were carried out after sacrificing the animals.Results: Errors to reach target and time taken to reach the target was found in BM experiment, elevated levels of antioxidants and hemoglobin wasfound reduced significantly in the DOX treated group when compared to the controls while histopathology of brain cells of DOX treated group alsoshowed reduction in hippocampal cellularity and cell death in hippocampal area suggesting evidence of oxidative damage caused by DOX treatment.Conclusion: Parameters in this study which not only conclusively show the damage caused to brain by DOX, but also estimates the changes caused toeach indicator by this drug.Keywords: Chemotherapy, Brain, Hippocampus, Oxidative stress

Epidemiological, clinical, haemato-biochemical and therapeutic evaluation of canine trypanosomosis in Mumbai

Evaluation of 20 confirmed clinical cases of canine trypanosomosis caused by Trypanosoma evansi in Mumbai from June 2012 to May 2013 was done to compile the basic information on parasitological, epidemiological, clinical, clinico-pathological and chemotherapeutic aspects. The disease was predominantly found in the localities having substantial equine and bovine population thus underlining the potential source for canine cases. Molecular analysis of few representative samples also confirmed the ability of the organisms to crossover from one species to other species of host. The disease was characterized by clinical signs such as depression, anorexia, anaemia, fever, splenomegaly, hepatomegaly and oedema of legs and paraclinical findings such as low levels of TEC, Hb and PCV indicating anaemic trend, elevated levels of alkaline phosphatase, AST, ALT and hyperglobulinaemia associated with reversing of albumin: globulin ratio. Hypoglycaemic trend noted in the study was found positively correlated with intensity of parasitaemia. Blood glucose levels were inversely related to degree of parasitaemia. The chemotherapeutic options, diminazeneaceturate and antrycideprosalt although cleared parasitaemia but failed to provide complete recovery, as 50% of cases eventually died in spite of specific chemotherapy suggesting some secondary involvement in the disease entity

Inhibition of WNT signaling attenuates self-renewal of SHH-subgroup medulloblastoma

The SMOOTHENED inhibitor vismodegib is FDA approved for advanced basal cell carcinoma (BCC), and shows promise in clinical trials for SONIC HEDGEHOG (SHH)-subgroup medulloblastoma (MB) patients. Clinical experience with BCC patients shows that continuous exposure to vismodegib is necessary to prevent tumor recurrence, suggesting the existence of a vismodegib-resistant reservoir of tumor-propagating cells. We isolated such tumor-propagating cells from a mouse model of SHH-subgroup MB and grew them as sphere cultures. These cultures were enriched for the MB progenitor marker SOX2 and formed tumors in vivo. Moreover, while their ability to self-renew was resistant to SHH inhibitors, as has been previously suggested, this self-renewal was instead WNT-dependent. We show here that loss of Trp53 activates canonical WNT signaling in these SOX2-enriched cultures. Importantly, a small molecule WNT inhibitor was able to reduce the propagation and growth of SHH-subgroup MB in vivo, in an on-target manner, leading to increased survival. Our results imply that the tumor- propagating cells driving the growth of bulk SHH-dependent MB are themselves WNT dependent. Further, our data suggest combination therapy with WNT and SHH inhibitors as a therapeutic strategy in patients with SHH-subgroup MB, in order to decrease the tumor recurrence commonly observed in patients treated with vismodegi

The effects of cold working on sensitization and intergranular corrosion behavior of AISI 304 stainless steel

The effects of prior cold rolling of up to an 80 pct reduction in thickness on the sensitization-desensitization behavior of Type AISI 304 stainless steel and its susceptibility to intergranular corrosion have been studied by electrochemical potentiokinetic reactivation (EPR) and Strauss-test methods. The results indicate that the prior deformation accelerated the sensitization as compared to the undeformed stainless steel. The deformed Type 304 stainless steel experienced desensitization at higher temperatures and times, and it was found to be enhanced by increased cold deformation. This could be attributed to the increased long-range chromium diffusion, possibly brought on by increasing pipe diffusion and vacancies. The role of the deformation-induced martensite (DIM) and texture, introduced by uniaxial cold rolling, on the sensitization-desensitization kinetics has also been discussed. This study could not reveal any systematic relationship between texture and the degree of sensitization (DOS) obtained. The effect of DIM on DOS seems to be pronounced at 500 °C when the steel retained significant amounts of DIM; however, the retained DIM is insignificant at higher sensitization times and temperatures

Predictors of mortality among elderly people living in a south Indian urban community; a 10/66 Dementia Research Group prospective population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Eighty percent of deaths occur in low and middle income countries (LMIC), where chronic diseases are the leading cause. Most of these deaths are of older people, but there is little information on the extent, pattern and predictors of their mortality. We studied these among people aged 65 years and over living in urban catchment areas in Chennai, south India.</p> <p>Methods</p> <p>In a prospective population cohort study, 1005 participants were followed-up after three years. Baseline assessment included sociodemographic and socioeconomic characteristics, health behaviours, physical, mental and cognitive disorders, disability and subjective global health.</p> <p>Results</p> <p>At follow-up, 257 (25.6%) were not traced. Baseline characteristics were similar to the 748 whose vital status was ascertained; 154 (20.6%) had died. The mortality rate was 92.5/1000 per annum for men and 51.0/1000 per annum for women. Adjusting for age and sex, mortality was associated with older age, male sex, having no friends, physical inactivity, smaller arm circumference, dementia, depression, poor self-rated health and disability. A parsimonious model included, in order of aetiologic force, male sex, smaller arm circumference, age, disability, and dementia. The total population attributable risk fraction was 0.90.</p> <p>Conclusion</p> <p>A balanced approach to prevention of chronic disease deaths requires some attention to proximal risk factors in older people. Smoking and obesity seem much less relevant than in younger people. Undernutrition is preventable. While dementia makes the largest contribution to disability and dependency, comorbidity is the rule, and more attention should be given to the chronic care needs of those affected, and their carers.</p

Association between tobacco use and body mass index in urban Indian population: implications for public health in India

BACKGROUND: Body mass index [BMI, weight (kg)/height (m(2))], a measure of relative weight, is a good overall indicator of nutritional status and predictor of overall health. As in many developing countries, the high prevalence of very low BMIs in India represents an important public health risk. Tobacco, smoked in the form of cigarettes or bidis (handmade by rolling a dried rectangular piece of temburni leaf with 0.15–0.25 g of tobacco) or chewed, is another important determinant of health. Tobacco use also may exert a strong influence on BMI. METHODS: The relationship between very low BMI (< 18.5 kg/m(2)) and tobacco use was examined using data from a representative cross-sectional survey of 99,598 adults (40,071 men and 59,527 women) carried out in the city of Mumbai (formerly known as Bombay) in western India. Participants were men and women aged ≥ 35 years who were residents of the main city of Mumbai. RESULTS: All forms of tobacco use were associated with low BMI. The prevalence of low BMI was highest in bidi-smokers (32% compared to 13% in non-users). For smokers, the adjusted odds ratio (OR) and 95% confidence interval (CI) were OR = 1.80(1.65 to 1.96) for men and OR = 1.59(1.09 to 2.32) for women, respectively, relative to non-users. For smokeless tobacco and mixed habits (smoking and smokeless tobacco), OR = 1.28(1.19 to 1.38) and OR = 1.83(1.67 to 2.00) for men and OR = 1.50(1.43 to 1.59) and OR = 2.19(1.90 to 3.41) for women, respectively. CONCLUSION: Tobacco use appears to be an independent risk factor for low BMI in this population. We conclude that in such populations tobacco control research and interventions will need to be conducted in concert with nutrition research and interventions in order to improve the overall health status of the population

Prevalence and correlates of smoking among urban adult men in Bangladesh: slum versus non-slum comparison

Khan MH, Khan A, Krämer A, Mori M. Prevalence and correlates of smoking among urban adult men in Bangladesh: slum versus non-slum comparison. BMC Public Health. 2009;9(1):149.Background: Smoking is one of the leading causes of premature death particularly in developing countries. The prevalence of smoking is high among the general male population in Bangladesh. Unfortunately smoking information including correlates of smoking in the cities especially in the urban slums is very scarce, although urbanization is rapid in Bangladesh and slums are growing quickly in its major cities. Therefore this study reported prevalences of cigarette and bidi smoking and their correlates separately by urban slums and non-slums in Bangladesh. Methods: We used secondary data which was collected by the 2006 Urban Health Survey. The data were representative for the urban areas in Bangladesh. Both slums and non-slums located in the six City Corporations were considered. Slums in the cities were identified by two steps, first by using the satellite images and secondly by ground truthing. At the next stage, several clusters of households were selected by using proportional sampling. Then from each of the selected clusters, about 25 households were randomly selected. Information of a total of 12,155 adult men, aged 15 59 years, was analyzed by stratifying them into slum (= 6,488) and non-slum (= 5,667) groups. Simple frequency, bivariable and multivariable logistic regression analyses were performed using SPSS. Results: Overall smoking prevalence for the total sample was 53.6% with significantly higher prevalences among men in slums (59.8%) than non-slums (46.4%). Respondents living in slums reported a significantly (P < 0.001) higher prevalence of smoking cigarettes (53.3%) as compared to those living in non-slums (44.6%). A similar pattern was found for bidis (slums = 11.4% and non-slums = 3.2%, P < 0.001). Multivariable logistic regression revealed significantly higher odds ratio (OR) of smoking cigarettes (OR = 1.12, 95% CI = 1.03-1.22), bidis (OR = 1.90, 95% CI = 1.58-2.29) and any of the two (OR = 1.23, 95% CI = 1.13-1.34) among men living in slums as compared to those living in non-slums when controlled for age, division, education, marital status, religion, birth place and types of work. Division, education and types of work were the common significant correlates for both cigarette and bidi smoking in slums and non-slums by multivariable logistic regressions. Other significant correlates of smoking cigarettes were marital status (both areas), birth place (slums), and religion (non-slums). Similarly significant factors for smoking bidis were age (both areas), marital status (slums), religion (non-slums), and birth place (both areas). Conclusion: The men living in the urban slums reported higher rates of smoking cigarettes and bidis as compared to men living in the urban non-slums. Some of the significant correlates of smoking e. g. education and division should be considered for prevention activities. Our findings clearly underscore the necessity of interventions and preventions by policy makers, public health experts and other stakeholders in slums because smoking was more prevalent in the slum communities with detrimental health sequelae

Multi-center feasibility study evaluating recruitment, variability in risk factors and biomarkers for a diet and cancer cohort in India

<p>Abstract</p> <p>Background</p> <p>India's population exhibits diverse dietary habits and chronic disease patterns. Nutritional epidemiologic studies in India are primarily of cross-sectional or case-control design and subject to biases, including differential recall of past diet. The aim of this feasibility study was to evaluate whether a diet-focused cohort study of cancer could be established in India, providing insight into potentially unique diet and lifestyle exposures.</p> <p>Methods</p> <p>Field staff contacted 7,064 households within three regions of India (New Delhi, Mumbai, and Trivandrum) and found 4,671 eligible adults aged 35-69 years. Participants completed interviewer-administered questionnaires (demographic, diet history, physical activity, medical/reproductive history, tobacco/alcohol use, and occupational history), and staff collected biological samples (blood, urine, and toenail clippings), anthropometric measurements (weight, standing and sitting height; waist, hip, and thigh circumference; triceps, sub-scapula and supra-patella skin fold), and blood pressure measurements.</p> <p>Results</p> <p>Eighty-eight percent of eligible subjects completed all questionnaires and 67% provided biological samples. Unique protein sources by region were fish in Trivandrum, dairy in New Delhi, and pulses (legumes) in Mumbai. Consumption of meat, alcohol, fast food, and soft drinks was scarce in all three regions. A large percentage of the participants were centrally obese and had elevated blood glucose levels. New Delhi participants were also the least physically active and had elevated lipids levels, suggesting a high prevalence of metabolic syndrome.</p> <p>Conclusions</p> <p>A high percentage of participants complied with study procedures including biological sample collection. Epidemiologic expertise and sufficient infrastructure exists at these three sites in India to successfully carry out a modest sized population-based study; however, we identified some potential problems in conducting a cohort study, such as limited number of facilities to handle biological samples.</p

Body Mass Index and Diabetes in Asia: A Cross-Sectional Pooled Analysis of 900,000 Individuals in the Asia Cohort Consortium

10.1371/journal.pone.0019930PLoS ONE66

Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment

Background High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic risk factors for all countries and regions from 1980 to 2010. Methods We used data for exposure to risk factors by country, age group, and sex from pooled analyses of populationbased health surveys. We obtained relative risks for the eff ects of risk factors on cause-specifi c mortality from metaanalyses of large prospective studies. We calculated the population attributable fractions for- each risk factor alone, and for the combination of all risk factors, accounting for multicausality and for mediation of the eff ects of BMI by the other three risks. We calculated attributable deaths by multiplying the cause-specifi c population attributable fractions by the number of disease-specifi c deaths. We obtained cause-specifi c mortality from the Global Burden of Diseases, Injuries, and Risk Factors 2010 Study. We propagated the uncertainties of all the inputs to the fi nal estimates. Findings In 2010, high blood pressure was the leading risk factor for deaths due to cardiovascular diseases, chronic kidney disease, and diabetes in every region, causing more than 40% of worldwide deaths from these diseases; high BMI and glucose were each responsible for about 15% of deaths, and high cholesterol for more than 10%. After accounting for multicausality, 63% (10\ub78 million deaths, 95% CI 10\ub71\u201311\ub75) of deaths from these diseases in 2010 were attributable to the combined eff ect of these four metabolic risk factors, compared with 67% (7\ub71 million deaths, 6\ub76\u20137\ub76) in 1980. The mortality burden of high BMI and glucose nearly doubled from 1980 to 2010. At the country level, age-standardised death rates from these diseases attributable to the combined eff ects of these four risk factors surpassed 925 deaths per 100 000 for men in Belarus, Kazakhstan, and Mongolia, but were less than 130 deaths per 100 000 for women and less than 200 for men in some high-income countries including Australia, Canada, France, Japan, the Netherlands, Singapore, South Korea, and Spain. Interpretation The salient features of the cardiometabolic disease and risk factor epidemic at the beginning of the 21st century are high blood pressure and an increasing eff ect of obesity and diabetes. The mortality burden of cardiometabolic risk factors has shifted from high-income to low-income and middle-income countries. Lowering cardiometabolic risks through dietary, behavioural, and pharmacological interventions should be a part of the globalresponse to non-communicable diseases