The cardiovascular effects of Aspalathus linearis supplementation in male Wistar rats receiving fixed-dose combination first-line antiretroviral therapy.

HIV-infected populations receiving antiretroviral therapy (ART) have an increased risk of cardiovascular disease. The beneficial cardiovascular effects of rooibos are well described; however, it is unknown whether rooibos ameliorates harmful ART-induced cardiovascular side effects. We investigated the cardiometabolic effects of rooibos co-treatment in rats receiving ART (efavirenz, emtricitabine, tenofovir) for nine weeks. Rooibos treatment reduced total cholesterol levels; however, triglyceride, phospholipid and thiobarbituric acidreactive substance levels were unaffected by ART, rooibos or combination treatment. In isolated hearts exposed to ischaemia-reperfusion injury, ART resulted in increased infarct sizes compared to controls, which was not observed when co-treated with rooibos. Vascular studies showed reduced aortic relaxation with ART, and improved relaxation when co-treated with rooibos. In conclusion, we show that rooibos treatment reduced total cholesterol levels in control rats, and that rooibos co-treatment ameliorated the harmful ART-induced cardiovascular effects. These findings are novel and warrant further studies into underlying mechanisms and clinical relevance.

Myocardial susceptibility to ischaemia/reperfusion in obesity: a re-evaluation of the effects of age.

BACKGROUND: Reports on the effect of age and obesity on myocardial ischaemia/reperfusion (I/R) injury and ischaemic preconditioning are contradictory. The aim of this study was to re-evaluate the effects of age and diet-induced obesity (DIO) on myocardial I/R injury and preconditioning potential. METHODS: Four groups of Wistar male rats were used: age-matched controls (AMC) receiving standard rat chow for (i) 16 weeks and (ii) 16 months respectively; DIO rats receiving a sucrose-supplemented diet for (iii) 16 weeks and (iv) 16 months respectively. The ages of groups (i) and (iii) were 22 weeks ("young") and groups (ii) and (iv) 17 months ("middle-aged") at time of experimentation. Isolated perfused working hearts were subjected to 35 min regional ischaemia/1 h reperfusion. Endpoints were infarct size (tetrazolium staining) and functional recovery. Hearts were preconditioned by 3 × 5 min ischaemia/5 min reperfusion. Results were processed using GraphPad Prism statistical software. RESULTS: Age did not affect baseline heart function before induction of ischaemia and I/R damage as indicated by infarct size and similar values were obtained in hearts from both age groups. Age also had no effect on functional recovery of hearts during reperfusion after regional ischaemia in AMC rats, but cardiac output during reperfusion was better in hearts from middle-aged than young DIO rats. The diet reduced infarct size in hearts from young rats (% of area at risk: AMC: 32.4 ± 3.6; DIO: 20.7 ± 2.9, p < 0.05), with no differences in hearts from middle-aged rats (AMC: 24.6 ± 4.6; DIO: 28.3 ± 13.5, p = NS). Compared to their respective AMC, diet-induced obesity had no significant effect on functional recovery of hearts from both age groups after exposure to regional ischaemia. When exposed to the more severe stress of global ischaemia, the functional recovery potential of middle-aged DIO rats appeared to be impeded compared to hearts of young DIO rats, while age had no effect on the functional recovery of AMC hearts. Preconditioning reduced infarct size in hearts from young control rats and both middle-aged groups, but not from young DIO rats. Age had a significant effect on functional recovery in preconditioning: it was improved in hearts from young control and DIO rats, but depressed in both middle-aged groups. CONCLUSIONS: The data showed that middle-age and obesity had no effect on baseline myocardial function and did not increase susceptibility to I/R damage upon exposure to regional ischaemia. On the contrary, obesity reduced I/R damage in young rats. Preconditioned aging hearts showed a decreased infarct size, but a reduction in functional recovery.

Sanguinarine non- versus re-circulation during isolated heart perfusion--a Jekyll and Hyde effect?

AIMS: In isolated rat heart perfusion experiments, drug administration occurs via retrograde perfusion. This can be done in the non-recirculating mode (coronary effluent is discarded), or recirculating mode (coronary effluent is collected and reused). It was recently observed in our lab while using sanguinarine, an MKP-1 inhibitor, that there were differences in outcomes depending on the mode of recirculation used. METHODS AND RESULTS: Hearts from control (C); diet-induced obese (DIO) Wistar rats and their age matched controls (AMC) were perfused on the rig. Hearts received buffer (control) , insulin, sanguinarine, insulin + sanguinarine combination or methanol (vehicle) for 15 mins pre- and 10 mins post-ischemia in either a non- or re-circulating manner. Hearts were subjected to 15 mins global ischemia and 30 mins reperfusion. Mechanical function was documented pre- and post-ischemia . When not-recirculated , sanguinarine alone and in combination with insulin in C, DIO and AMC groups, caused a significant decrease in functional recovery during reperfusion. However, when the coronary effluent was recirculated, hearts perfused with sanguinarine or sanguinarine + insulin exhibited a significant recovery in function when compared with their non-recirculation counterparts (p < 0.01). No differences were seen with either control, insulin nor vehicle hearts. CONCLUSION: Sanguinarine elicited a vast improvement in perfusion outcomes when recirculated compared to non-recirculation . Since this was seen during perfusion only when sanguinarine was present, it is possible that recirculating reperfusion of the drug caused profound changes in its composition. More investigation is needed into the mechanisms involved. Thus caution should be exercised by researchers when designing a perfusion protocol for drug research.

The effect of creatine supplementation on myocardial function, mitochondrial respiration and susceptibility to ischaemia/reperfusion injury in sedentary and exercised rats.

AIM: To investigate the effects of dietary creatine supplementation alone and in combination with exercise on basal cardiac function, susceptibility to ischaemia/reperfusion injury and mitochondrial oxidative function. There has been an increase in the use of creatine supplementation among sports enthusiasts, and by clinicians as a therapeutic agent in muscular and neurological diseases. The effects of creatine have been studied extensively in skeletal muscle, but not in the myocardium. METHODS: Male Wistar rats were swim-trained for 8 weeks, 5 days per week. Hearts were excised and either freeze-clamped for biochemical analysis or perfused on the isolated heart perfusion system to assess function and ischaemia/reperfusion tolerance. Mechanical function was documented in working heart and retrograde mode. The left coronary artery was ligated and infarct size determined. Mitochondrial oxidative capacity was quantified. RESULTS: Aortic output recovery of hearts from the sedentary controls (CSed) was significantly higher than those from creatine-supplemented sedentary (CrSed), creatine-supplemented exercised (CrEx) as well as control exercised (CEx) groups. Ischaemic contracture of hearts from CrEx was significantly higher than that of CSed. There were no differences in infarct size and mitochondrial oxygen consumption. CONCLUSION: This study suggests that creatine supplementation has no effects on basal cardiac function but reduces myocardial tolerance to ischaemia in hearts from exercise-trained animals, by increasing the ischaemic contracture and decreasing reperfusion aortic output. Exercise training alone also significantly decreased aortic output recovery. However, the exact mechanisms for these adverse myocardial effects are unknown and need further investigation.

AMP kinase activation and glut4 translocation in isolated cardiomyocytes.

Activation of AMP-activated protein kinase (AMPK) results in glucose transporter 4 (GLUT4) translocation from the cytosol to the cell membrane, and glucose uptake in the skeletal muscles. This increased activation of AMPK can be stimulated by a pharmacological agent, AICAR (5' -aminoimidazole-4-carboxamide ribonucleoside), which is converted intracellularly into ZMP (5' -aminoimidazole-4-carboxamideribonucleosidephosphate), an AMP analogue. We utilised AICAR and ZMP to study GLUT4 translocation and glucose uptake in isolated cardiomyocytes. Adult ventricular cardiomyocytes were treated with AICAR or ZMP, and glucose uptake was measured via [3H] -2-deoxyglucose accumulation. PKB/Akt, AMPK and acetyl-CoA-carboxylase phosphorylation and GLUT4 translocation were detected by Western blotting or flow cytometry. AICAR and ZMP promoted AMPK phosphorylation. Neither drug increased glucose uptake but on the contrary, inhibited basal glucose uptake, although GLUT4 translocation from the cytosol to the membrane occurred. Using flow cytometry to detect the exofacial loop of the GLUT4 protein, we showed ineffective insertion in the membrane under these conditions. Supplementing with nitric oxide improved insertion in the membrane but not glucose uptake. We concluded that activation of AMPK via AICAR or ZMP was not sufficient to induce GLUT4-mediated glucose uptake in isolated cardiomyocytes. Nitric oxide plays a role in proper insertion of the protein in the membrane but not in glucose uptake.

Gender differences in alcohol consumption and adverse drinking consequences: cross-cultural patterns.

AIMS: To examine the consistency and/or variability of gender differences in drinking behavior cross-culturally. DESIGN, SETTING, PARTICIPANTS: Women's and men's responses in 16 general population surveys from 10 countries, analyzed by members of the International Research Group on Gender and Alcohol. MEASUREMENTS: Comparable measures of drinking, versus abstention, typical drinking frequencies and quantities, heavy episodic drinking, intoxication, morning drinking, and alcohol-related family and occupational problems. FINDINGS: Women and men differed little in the probability of currently drinking versus abstaining, but men consistently exceeded women in typical drinking frequencies and quantities and in rates of heavy drinking episodes and adverse drinking consequences, while women were consistently more likely than men to be life-time abstainers. In older age groups, both men and women drank smaller quantities of alcohol and were more likely to stop drinking altogether, but drinking frequencies did not change consistently with age. CONCLUSIONS: A theoretical synthesis proposes that gender roles may amplify biological differences in reactions to alcohol, and that gender differences in drinking behavior may be modified by macrosocial factors that modify gender role contrasts.

Socio-economic, migrant and geographic differentials in coronary heart disease occurrence in New South Wales.

OBJECTIVE: This study examines the variation in coronary heart disease (CHD) mortality and acute myocardial infarction (AMI) by socio-economic status (SES), country of birth (COB) and geography (urban/rural) in the total population of New South Wales (Australia) in 1991-95. METHOD: CHD deaths and AMI are from complete enumerations of deaths and hospital admissions, respectively; and population denominators are from census information. Data are examined separately by sex, and comparisons of SES groups (based on municipalities), COB and region are analysed using Poisson regression, after adjustment for age. RESULTS: The study identified higher risk for AMI admissions and CHD mortality in lower SES populations with significant linear trends, for both sexes, adjusted for age, region and COB. According to the population attributable fractions (PAF), 23-41% of the risk of CHD occurrence is due to SES lower than the highest quartile. The higher age-adjusted risk for CHD occurrence in rural and remote populations for both sexes, compared with urban communities, was lessened by adjustment for COB, and all but abolished when also adjusted for SES.COB analysis indicated significantly lower age-adjusted AMI admissions and CHD mortality compared with the Australian-born. CONCLUSIONS: Higher risks for CHD in rural populations compared with the capital city (Sydney) are due, in part, to lower SES, lesser migrant composition. IMPLICATIONS: Strategies for reducing CHD differentials should consider demographic factors and the fundamental need to reduce socio-economic inequalities, as well as targeting appropriate prevention measures.

Unemployment and health: the healthcare system's role.

Experts from the South Western Sydney Area Health Service and the University of New South Wales say there are few reports of healthcare interventions to address the impact of unemployment on health. They outline possible strategies, which include providing accessible and appropriate healthcare; developing the healthcare system's capacity to deal with the health problems of unemployed people; collaborating with other agencies and sectors working on this issue; acting as an advocate for unemployed people; undertaking research; and providing training, work experience and employment opportunities within the healthcare system. Long term solutions lie in increasing employment and training opportunities. Nevertheless, there is a clear role for the healthcare system in reducing the health impacts of unemployment and ensuring that poor health does not act as a barrier to returning to work.

Alcohol disorders in Canada as indicated by the CAGE questionnaire.

OBJECTIVE: To describe alcohol disorders in the general Canadian population, using as a standard indicator the CAGE questionnaire (Have you felt you needed to cut down on your drinking? Have you felt annoyed by criticism of your drinking? Have you felt guilty about drinking? Have you felt you needed a drink first thing in the morning [eye-opener]?). DESIGN: Secondary analysis of data from Canada's Alcohol and Other Drugs Survey (CADS), a national telephone survey conducted in 1994 of a representative sample of 12,155 people aged 15 years or more. PARTICIPANTS: The CAGE questionnaire was administered to 5894 drinkers who had consumed alcohol in the 12 months before the CADS survey. MAIN OUTCOME MEASURES: Respondents with positive (2 or more affirmative responses) and negative results on the CAGE questionnaire were compared as to demographic characteristics, alcohol consumption and harmful consequences of their drinking. Independent predictors of a positive result were identified by means of logistic regression analysis. RESULTS: A total of 5.8% of CAGE-tested current drinkers had a positive result on the past-year CAGE in 1994. The proportion of respondents reporting alcohol-related problems in one or more areas of their life was 7 times greater among drinkers with a positive result on the CAGE questionnaire than among those with a negative result (66.8% v. 9.5%) (p < 0.0001). When all demographic characteristics were controlled for simultaneously, male sex, residence in the Atlantic provinces, Quebec or the Prairies, single/never married or divorced/separated marital status, and low education level were found to be independent risk factors for a positive result on the CAGE questionnaire. About 85% of the respondents with a positive result had not sought help for their drinking. Applying the estimated sensitivity and specificity of the CAGE questionnaire in detecting alcohol dependence, as per criteria of the Diagnostic and Statistical Manual, in a general US population, the authors estimated that 4.1% of Canadians had an alcohol dependence in 1994. CONCLUSION: The large proportion of current drinkers with a positive result on the CAGE questionnaire who did not seek help for their drinking underscores the need for identification and brief interventions by physicians. Further research is needed to elucidate the underlying reasons for regional differences in CAGE status.

Describing and predicting alcohol use-related harm: an analysis of the Yukon Alcohol and Drug Survey.

During 1990 the Yukon Bureau of Statistics conducted an alcohol and drug survey with a sample of 1,348 residents of the Territory, aged 15 and over. Over three-quarters of the sample reported experiencing at least one type of harm from others' drinking during the past year, and over a half experienced two or more types of harm. Among the main predictors of prevalence and extent of harm were respondents' age (younger), a greater number of drinks per occasion, close associates with alcohol problems, and residing in smaller communities. The results are discussed in terms of their relevance to identifying vulnerable groups and informing policy aimed at reducing alcohol use-related harm.

High sugar intake in a group of women on methadone maintenance in south western Sydney, Australia.

Nutritional assessment comprising dietary and anthropometric measurements was conducted in a group of 86 women attending a methadone maintenance clinic in South Western Sydney, Australia. Dietary data were obtained by two 24-hour recall interviews using a standardized interview format. Nutrient intake was analysed using the NUTTAB data base of Australian foods (1992). Mean age of the sample was 29.8 (range 18-46) years and mean body mass index was 22.7 (range 16.2-43.4) kg/m2. The diet of the study group was characterized by a low energy intake of 6.48 MF (95% CI 6.02-6.94), a high sugars intake of 122 g (95% CI 112-132), a high percentage of total energy (31%, 95% CI 29-32) derived from sugars, and a low dietary fibre intake of 10.7 g (95% CI 9.7-12.3). This eating pattern may contribute to the high prevalence of a dental caries and chronic constipation observed in the group. The results pattern also support anecdotal evidence of a craving for sweetness described by addicts. Despite the low energy intake, body mass indices of the group were no different from the normal population. It is possible that 2 days' intake was insufficient to accurately measure accustomed diet in this group of women. Alternatively, the low intake may be a consequence of their largely sedentary life-styles.

General practitioners' promotion of healthy life styles: what patients think.

The study examined the prevalence of cigarette smoking, alcohol consumption, exercising to keep fit and dieting to lose weight among general practice patients, and patients' perceptions of the role of the general practitioner in advising about life style. A cross-sectional survey using a self-administered questionnaire was completed by 13,017 patients aged 18 to 70 years who were attending one of 119 general practitioners from 40 group practices in metropolitan Sydney over a six- to eight-week period. More women than men reported dieting to lose weight, just over half of the men and women were exercising regularly to keep fit, 35 per cent of men and 29 per cent of women reported smoking, and 12 per cent of men and 10 per cent of women were drinking alcohol at levels considered hazardous or harmful. More young people were smoking, drinking hazardously or harmfully, dieting to lose weight and exercising than the older age groups, and their smoking rates exceeded those of the general population. Most patients reported that general practitioners should be interested in their life-style behaviours, particularly smoking. Substantially fewer patients (particularly women who drank excessively) reported receiving advice about their habits. General practitioners were more likely to give advice when smoking and drinking levels were very high. There were discrepancies between patients' expectations of the doctor's role in promoting healthy life styles, and their likelihood of receiving advice. Doctors could reduce the diseases associated with unhealthy practices. Developments in medical training in the 1990s may extend the way they engage in advising on issues of life style.

Controlled evaluation of a general practice-based brief intervention for excessive drinking.

In a controlled evaluation of general practitioner (GP)-based brief intervention, 378 excessive drinkers identified opportunistically by screening in 40 group practices in metropolitan Sydney were assigned to groups receiving: (i) a five-session intervention by the GP (the Alcoholscreen Program); (ii) a single session of 5 minutes' advice by the GP plus a self-help manual (minimal intervention); (iii) an alcohol-related assessment but no intervention; (iv) neither intervention nor assessment. Among all patients allocated to receive it, the Alcoholscreen Program did not result in a significantly greater reduction in consumption at follow-up than control conditions but patients offered Alcoholscreen reported a significantly greater reduction in alcohol-related problems in the period to 6 months follow-up. A greater proportion of patients who returned for the second Alcoholscreen visit were drinking below recommended levels at follow-up than in the remainder of the sample. There was no evidence that minimal intervention or alcohol-related assessment were effective in reducing alcohol consumption or problems. Implications for further research into GP-based brief interventions are discussed.

Ethics decision-making in Australian hospitals.

OBJECTIVE: To describe the methods used to resolve ethical issues in hospitals throughout Australia. DESIGN: A descriptive study from data collected by a questionnaire survey of Australian public and private hospitals. PARTICIPANTS: Hospital administrators and employees nominated by hospital administrators. RESULTS: Completed questionnaires were received from 739 (74%) hospitals. Methods used to resolve ethical issues included personal reflection, discussion between health professionals and discussion between health professionals and patients. A variety of committees were identified as having some role in the discussion of ethical issues, but only a small number of hospitals had established ethics committees. CONCLUSION: Doctor-patient interaction and discussion between practitioners are the most common methods used to resolve ethical issues. Various committees are also used and, of these, ethics committees are not the most commonly consulted.

Postural stability, falls and fractures in the elderly: results from the Dubbo Osteoporosis Epidemiology Study.

OBJECTIVE: To assess measures of postural stability in a large population of persons aged over 60 years in order to compare performance between fallers and non-fallers and relate postural stability to fracture prevalence. METHODS: The sensorimotor, visual and balance functions were measured in 1762 ambulatory, community-dwelling patients aged between 60 and 100 years (mean age, 70.1 years) living in a large semi-urban Australian city. A history of recent falls and fractures was recorded at the time of assessment. RESULTS: The prevalence of impairment in all tests increased with age. Men performed significantly better than women in tests of muscle strength, visual field dependence, sway on the floor with eyes open and dynamic balance. In the 12 months before testing, 72.3% of the patients experienced no falls, 18.4% fell only once and 9.3% fell on two or more occasions. Multiple fallers had weaker quadriceps, poorer tactile sensitivity, greater visual field dependence and greater body sway than other patients. Test scores for once-only fallers were mostly between those for non-fallers and multiple fallers. Those who suffered recent fall-related fractures had significantly reduced tactile sensitivity and quadriceps strength and increased body sway. Postural stability was also impaired in patients taking psychoactive and/or anti-hypertensive medications. CONCLUSION: Tests of postural stability can identify, independently of age, individuals living in the community who are at risk of falls and fall-related fractures.