Determination of glutathione transferase (GSTT1-1) activities in different tissues based on formation of radioactive metabolites using 35S-glutathione

A new system has been developed to determine enzyme activities of glutathione transferase θ (GSTT1-1) based on radiometric product detection resulting from the enzymic reaction of methyl chloride with 35S-labelled glutathione. In principle, the method is universally applicable for determination of glutathione transferase activities towards a multiplicity of substrates. The method distinguishes between erythrocyte GSTT1-1 activities of human 'non-conjugators', 'low conjugators' and 'high conjugators'. Application to cytosol preparations of livers and kidneys of male and female Fischer 344 and B6C3F1 mice reveals differential GSTT1-1 activities in hepatic and renal tissues. These ought to be considered in species-specific modellings of organ toxicities of chlorinated hydrocarbons.

Genetic susceptibility to environmental toxicants : the interface between human and experimental studies in the development of new toxicological concepts

The growing knowledge of the genetic polymorphisms of enzymes metabolising xenobiotics in humans and their connections with individual susceptibility towards toxicants has created new and important interfaces between human epidemiology and experimental toxicology. The results of molecular epidemiological studies may provide new hypotheses and concepts, which call for experimental verification, and experimental concepts may obtain further proof by molecular epidemiological studies. If applied diligently, these possibilities may be combined to lead to new strategies of human-oriented toxicological research. This overview will present some outstanding examples for such strategies taken from the practically very important field of occupational toxicology. The main focus is placed on the effects of enzyme polymorphisms of the xenobiotic metabolism in association with the induction of bladder cancer and renal cell cancer after exposure to occupational chemicals. Also, smoking and induction of head and neck squamous cell cancer are considered.

DNA binding study of isophorone in rats and mice

Following isophorone exposure, in a 2-year study with F344 rats and B6C3F1 mice performed under the National Toxicology Program (NTP), an elevated incidence of tumors was observed in male rats (kidney tumors) and male mice (liver tumors). Female rats and mice showed no elevation of tumor rates by isophorone (NTP 1986).

Development of the OnTrack Diabetes program

Background: Type 2 diabetes affects an estimated 347 million people worldwide and often leads to serious complications including blindness, kidney disease, and limb amputation. Comorbid dysphoria is common and is an independent risk factor for poor glycaemic control. Professional support for diabetes self-management and dysphoria has limited availability and involves high costs, especially after regular hours, and in rural and remote areas. Web-based cognitive behavior therapy offers highly accessible, acceptable, and cost-effective support for people with diabetes. This paper describes the development of OnTrack Diabetes, a self-guided, Web-based program to promote improved physical and emotional self-management in people with Type 2 diabetes. Objective: The objective of the study is to describe the development of the OnTrack Diabetes program, which is a self-guided, Web-based program aimed to promote euthymia and improved disease self-management in people with Type 2 diabetes. Methods: Semistructured interviews with 12 general practitioners and 13 patients with Type 2 diabetes identified enablers of and barriers to effective diabetes self-management, requirements for additional support, and potential program elements. Existing resources and research data informed the development of content, and consultants from relevant disciplines provided feedback on draft segments and reviewed the program before release. Using a self-guided delivery format contained costs, in addition to adapting program features and modules from an existing OnTrack program. Results: A separate paper describes the protocol for a randomized controlled trial to provide this required evaluation. Conclusions: Development of the OnTrack Diabetes program demonstrates strategies that help ensure that a program is acceptable to users. The next stages involve testing users’ experiences and examining the program’s effectiveness and cost-effectiveness in randomized controlled trials.

Meeting the nutrition challenge of stage 3 renal failure : considerations for nursing practice

Self-care management is needed for effective management of chronic kidney disease. The main aim for treatment or management of chronic kidney disease is to delay the worsening of kidney function, and to prevent or to manage the co-morbidities. Selfcare management is not easy, and patients will face many challenges, especially when they cannot get use to the new treatment plan. One of the challenges they face is dietary restriction, which is a very important aspect in any self-care management programme. Chronic kidney disease patients require a low-protein, low-sodium, low-potassium, and low-phosphorus diet. There are several strategies patients can undertake to ensure adherence, such as self-monitoring their dietary habits and type of food consumed using a food diary; involving social support, such as family members and spouse to help them to adhere to their diet restrictions; setting goals and providing positive reinforcement when they achieved the targeted goals; joining self-management programmes to equip themselves with the necessary skills so that they can better adhere to the treatment regimes, including diet restriction; and lastly, having the knowledge about their regime, and using this knowledge to help them understand and improve their adherence.

Effect of tocopherol on atherosclerosis, vascular function and inflammation in Apolipoprotein E knockout mice with subtotal nephrectomy

Background/Aims: Inflammation and endothelial dysfunction contribute to cardiovascular disease, prevalent in chronic kidney disease (CKD). Antioxidant supplements such as tocopherols may reduce inflammation and atherosclerosis. This study aimed to investigate the effect of tocopherol supplementation on vascular function, aortic plaque formation, and inflammation in apolipoprotein E−/− mice with 5/6 nephrectomy as a model of combined cardiovascular and kidney disease. Methods: Nephrectomized mice were assigned to a normal chow diet group (normal chow), a group receiving 1000 mg/kg diet of α-tocopherol supplementation or a group receiving 1000 mg/kg diet mixed-tocopherol (60% γ-tocopherol). Results: Following 12 weeks, in vitro aortic endothelial-independent relaxation was enhanced with both α-tocopherol and mixed-tocopherol (P < 0.05), while mixed-tocopherol enhanced aortic contraction at noradrenaline concentrations of 3 × 10−7 M to 3 × 10−5 M (P < 0.05), when compared to normal chow. Supplementation with α- and mixed-tocopherol reduced systemic concentrations of IL-6 (P < 0.001 and P < 0.001, respectively) and IL-10 (P < 0.05 and P < 0.001, respectively), while α-tocopherol also reduced MCP-1 (P < 0.05) and tumor necrosis factor (TNF)-α (P < 0.05). Aortic sinus plaque area was significantly reduced with α-tocopherol supplementation when compared to normal chow (P < 0.01). Conclusion: Tocopherol supplementation favorably influenced vascular function and cytokine profile, while it was also effective in reducing atherosclerosis in the apolipoprotein E−/− mouse with CKD.

Estimating the burden of disease attributable to excess body weight in South Africa in 2000

Objective. To estimate the burden of disease attributable to excess body weight using the body mass index (BMI), by age and sex, in South Africa in 2000. Design. World Health Organization comparative risk assessment (CRA) methodology was followed. Re-analysis of the 1998 South Africa Demographic and Health Survey data provided mean BMI estimates by age and sex. Populationattributable fractions were calculated and applied to revised burden of disease estimates. Monte Carlo simulation-modelling techniques were used for the uncertainty analysis. Setting. South Africa. Subjects. Adults 30 years of age. Outcome measures. Deaths and disability-adjusted life years (DALYs) from ischaemic heart disease, ischaemic stroke, hypertensive disease, osteoarthritis, type 2 diabetes mellitus, and selected cancers. Results. Overall, 87% of type 2 diabetes, 68% of hypertensive disease, 61% of endometrial cancer, 45% of ischaemic stroke, 38% of ischaemic heart disease, 31% of kidney cancer, 24% of osteoarthritis, 17% of colon cancer, and 13% of postmenopausal breast cancer were attributable to a BMI 21 kg/m2. Excess body weight is estimated to have caused 36 504 deaths (95% uncertainty interval 31 018 - 38 637) or 7% (95% uncertainty interval 6.0 - 7.4%) of all deaths in 2000, and 462 338 DALYs (95% uncertainty interval 396 512 - 478 847) or 2.9% of all DALYs (95% uncertainty interval 2.4 - 3.0%). The burden in females was approximately double that in males. Conclusions. This study shows the importance of recognising excess body weight as a major risk to health, particularly among females, highlighting the need to develop, implement and evaluate comprehensive interventions to achieve lasting change in the determinants and impact of excess body weight.

Transcriptome analyses of amoebic gill disease-affected atlantic salmon (Salmo salar) tissues reveal localized host gene suppression

The transcriptome response of Atlantic salmon (Salmo salar) displaying advanced stages of amoebic gill disease (AGD) was investigated. Naïve smolt were challenged with AGD for 19 days, at which time all fish were euthanized and their severity of infection quantified through histopathological scoring. Gene expression profiles were compared between heavily infected and naïve individuals using a 17 K Atlantic salmon cDNA microarray with real-time quantitative RT-PCR (qPCR) verification. Expression profiles were examined in the gill, anterior kidney, and liver. Twenty-seven transcripts were significantly differentially expressed within the gill; 20 of these transcripts were down-regulated in the AGD-affected individuals compared with naïve individuals. In contrast, only nine transcripts were significantly differentially expressed within the anterior kidney and five within the liver. Again the majority of these transcripts were down-regulated within the diseased individuals. A down-regulation of transcripts involved in apoptosis (procathepsin L, cathepsin H precursor, and cystatin B) was observed in AGD-affected Atlantic salmon. Four transcripts encoding genes with antioxidant properties also were down-regulated in AGD-affected gill tissue according to qPCR analysis. The most up-regulated transcript within the gill was an unknown expressed sequence tag (EST) whose expression was 218-fold (± SE 66) higher within the AGD affected gill tissue. Our results suggest that Atlantic salmon experiencing advanced stages of AGD demonstrate general down-regulation of gene expression, which is most pronounced within the gill. We propose that this general gene suppression is parasite-mediated, thus allowing the parasite to withstand or ameliorate the host response. © 2008 Springer Science+Business Media, LLC.

Global, regional, and national age–sex specifi c all-cause and cause-specifi c mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65·3 years (UI 65·0–65·6) in 1990, to 71·5 years (UI 71·0–71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8–48·2) to 54·9 million (UI 53·6–56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25–39 years and older than 75 years and for men aged 20–49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.

Voluntary exercise decreases atherosclerosis in nephrectomised ApoE knockout mice

Cardiovascular disease is the main cause of morbidity and mortality in patients with kidney disease. The effectiveness of exercise for cardiovascular disease that is accelerated by the presence of chronic kidney disease remains unknown. The present study utilized apolipoprotein E knockout mice with 5/6 nephrectomy as a model of combined kidney disease and cardiovascular disease to investigate the effect of exercise on aortic plaque formation, vascular function and systemic inflammation. Animals were randomly assigned to nephrectomy or control and then to either voluntary wheel running exercise or sedentary. Following 12-weeks, aortic plaque area was significantly (p<0.05, d=1.2) lower in exercising nephrectomised mice compared to sedentary nephrectomised mice. There was a strong, negative correlation between average distance run each week and plaque area in nephrectomised and control mice (r=–0.76, p=0.048 and r=–0.73, p=0.062; respectively). In vitro aortic contraction and endothelial-independent and endothelial-dependent relaxation were not influenced by exercise (p>0.05). Nephrectomy increased IL-6 and TNF-α concentrations compared with control mice (p<0.001 and p<0.05, respectively), while levels of IL-10, MCP-1 and MIP-1α were not significantly influenced by nephrectomy or voluntary exercise (p>0.05). Exercise was an effective non-pharmacologic approach to slow cardiovascular disease in the presence of kidney disease in the apolipoprotein E knockout mouse.

The effectiveness of education or behavioral interventions on adherence to phosphate control in adults receiving hemodialysis: A systematic review protocol

The objective of this review is to identify the effectiveness of education or behavioral interventions on adherence to phosphate control in adults with end stage kidney disease (ESKD) receiving hemodialysis (HD).

Saudi Arabian adult intensive care unit pressure ulcer incidence and risk factors: A prospective cohort study

The purpose of this study was to identify pressure ulcer (PU) incidence and risk factors that are associated with PU development in patients in two adult intensive care units (ICU) in Saudi Arabia. A prospective cohort study design was used. A total of 84 participants were screened second daily basis until discharge or death, over a consecutive 30-day period, out of which 33 participants with new PUs were identified giving a cumulative hospital-acquired PU incidence of 39·3% (33/84 participants). The incidence of medical devices-related PUs was 8·3% (7/84). Age, length of stay in the ICU, history of cardiovascular disease and kidney disease, infrequent repositioning, time of operation, emergency admission, mechanical ventilation and lower Braden Scale scores independently predicted the development of a PU. According to binary logistic regression analyses, age, longer stay in ICU and infrequent repositioning were significant predictors of all stages of PUs, while the length of stay in the ICU and infrequent repositioning were associated with the development of stages II-IV PUs. In conclusion, PU incidence rate was higher than that reported in other international studies. This indicates that urgent attention is required for PU prevention strategies in this setting.

Job satisfaction, stress and burnout in haemodialysis nurses

Haemodialysis nurses provide health care for people with end stage kidney disease leading to a unique, intense and complex interaction between nurses and patients. This study involved the development of a model which explains the relationships between the work environment, job satisfaction, stress and burnout of haemodialysis nurses in Australia and New Zealand. Results from this study identified that haemodialysis nurses, while being satisfied by their jobs, were also experiencing high levels of burnout. This study's novel contribution could lead to improving the retention of the nursing workforce which is crucial due to the growing global burden of chronic disease.