Zinc status of northern Tasmanian adults.

Information regarding Zn status in the Australian population is very limited. Mild deficiencies in Zn have been associated with CVD, impaired immune function and poor healing. A cross-sectional study of 497 northern Tasmanian adults (24-82 years of age) was conducted to assess Zn status. Dietary intakes were assessed by FFQ and serum concentrations of Zn were evaluated using International Zinc Nutrition Consultative Group methodology. Mean Zn intakes were 12·6 (sd 4·4) mg/d for men and 10·9 (sd 3·6) mg/d for women. It was found that 52 % of men but only 9 % of women consumed less than the Australia/New Zealand estimated average requirement for Zn. Mean serum Zn was 13·0 (sd 2·4) µmol/l in men and 13·0 (sd 2·5) µmol/l in women. Overall, 15 % of men and 7 % of women had low serum Zn levels. Furthermore, low serum Zn was observed in 18 % of men 50 years or older and 30 % of men 70 years or older. The present results suggest that mild Zn deficiency may be prevalent in older Tasmanian adults, particularly men; and due to the importance of Zn in many areas of health, this could be of public health concern.

Effects of atorvastatin on oxidative stress in chronic kidney disease.

AIM: Statins have pleiotropic effects that include attenuation of oxidative stress that may be relevant for chronic kidney disease (CKD) patients. We investigated the effect of long-term atorvastatin therapy on oxidative stress biomarkers in CKD patients. METHODS: This was a pre-specified secondary analysis of data from a randomized, double-blind, placebo-controlled trial (Lipid lowering and Onset of Renal Disease, LORD) in CKD patients. Participants received 10 mg/day atorvastatin (n = 47) or placebo (n = 39) for 3 years. Plasma measures (total F2-isoprostanes, malondialdehyde. protein carbonyls, uric acid, glutathione peroxidase (GPx) activity and total antioxidant capacity (TAC) ) were performed at baseline and at 3 years. Age and sex matched participants (n = 34) with normal kidney function were controls. RESULTS: CKD patients had significantly (P < 0.05) increased F2-isoprostanes and uric acid and decreased GPx activity compared with controls. When comparing the treatment (atorvastatin (A) vs placebo (P) ) change from baseline to 3 years, there were no significant differences (P > 0.05) in the group difference of the change values: (mean (95% CI), F2-isoprostanes = 5.3 (-29.2 to 39.8) pg/mL, protein carbonyls = 0.03 (-0.13 to 0.19) nmol/mg, GPx activity = -0.10 (-4.73 to 4.52) (U/L), uric acid = 8.8 (-33.9 to 51.6) µmol/L or TAC = -0.03 (-0.10 to 0.04) mmol/L. A significant difference (P = 0.04) in the change in malondialdehyde between groups, 1.52(0.09 to 2.96) µmol/L, was due to a large decrease in the placebo group. CONCLUSION: CKD patients had elevated oxidative stress that was not attenuated by atorvastatin 10 mg/day for 3 years.

Can probiotic yogurt prevent diarrhoea in children on antibiotics? A double-blind, randomised, placebo-controlled study.

OBJECTIVE: To estimate the efficacy of a probiotic yogurt compared to a pasteurised yogurt for the prevention of antibiotic-associated diarrhoea in children. DESIGN AND SETTING: This was a multisite, randomised, double-blind, placebo-controlled clinical trial conducted between September 2009 and 2012. The study was conducted through general practices and pharmacies in Launceston, Tasmania, Australia. PARTICIPANTS AND INTERVENTIONS: Children (aged 1-12 years) prescribed antibiotics, were randomised to receive 200 g/day of either yogurt (probiotic) containing Lactobacillus rhamnosus GG (LGG), Bifidobacterium lactis (Bb-12) and Lactobacillus acidophilus (La-5) or a pasteurised yogurt (placebo) for the same duration as their antibiotic treatment. OUTCOMES: Stool frequency and consistency were recorded for the duration of treatment plus 1 week. Primary outcome was stool frequency and consistency, classified at different levels of diarrhoea severity. Due to the small number of cases of diarrhoea, comparisons between groups were made using Fisher's exact analysis. RESULTS: 72 children commenced and 70 children (36 placebo and 34 probiotic) completed the trial. There were no incidents of severe diarrhoea (stool consistency ≥6, ≥3 stools/day for ≥2 consecutive days) in the probiotic group and six in the placebo group (Fisher's exact p=0.025). There was also only one episode of minor diarrhoea (stool consistency ≥5, ≥2 stools/day for ≥2 days in the probiotic group compared to 21 in the placebo group (Fisher's exact p<0.001). The probiotic group reported fewer adverse events (1 had abdominal pain, 1 vomited and 1 had headache) than the placebo group (6 had abdominal pain, 4 had loss of appetite and 1 had nausea). CONCLUSIONS: A yogurt combination of LGG, La-5 and Bb-12 is an effective method for reducing the incidence of antibiotic-associated diarrhoea in children. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12609000281291.

Persistence of Human Papillomavirus, Overexpression of p53, and Outcomes of Patients After Endoscopic Ablation of Barrett's Esophagus.

We investigated the role of high-risk human papillomavirus (hr-HPV) in patients with Barrett's dysplasia and adenocarcinoma (EAC). Clearance vs persistence of HPV (DNA, E6 or E7 mRNA, and p16INK4A protein) and overexpression or mutation of p53 were determined for 40 patients who underwent endotherapy for Barrett's dysplasia or EAC. After ablation, dysplasia or neoplasia was eradicated in 34 subjects (24 squamous, 10 intestinal metaplasia). Six patients had detectable lesions after treatment; 2 were positive for transcriptionally active hr-HPV, and 4 had overexpression of p53. Before endotherapy, 15 patients had biologically active hr-HPV, 13 cleared the infection with treatment, and dysplasia or EAC was eliminated from 12 patients. One patient who cleared HPV after ablation acquired a p53 mutation, and their cancer progressed. Of 13 patients with overexpression of p53 before treatment, 10 cleared the p53 abnormality after ablation with eradication of dysplasia or neoplasia, whereas 3 of 13 had persistent p53 mutation-associated dysplasia after endotherapy (P = .004). Immunohistochemical and sequence analyses of p53 produced concordant results for 36 of 40 samples (90%). Detection of dysplasia or neoplasia after treatment was associated with HPV persistence or continued p53 overexpression.

Effects of atorvastatin on biomarkers of inflammation in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with inflammation. The effects of atorvastatin on biomarkers of inflammation were assessed in CKD patients in the LORD trial. METHODS: 117 patients with serum creatinine >120 µmol/L were randomized to receive atorvastatin 10 mg/day (56) or placebo (61) and followed for a mean of 2.5 years. 33 individuals with normal kidney function were controls. Outcomes included comparison of changes in pentraxin-3 (PTX3), TNF-α, CRP, IL-6, IL-8, and IL-10 between atorvastatin and placebo-treated patients. RESULTS: At baseline, compared with controls, CKD patients had increased PTX3 (mean, 1.08 vs. 0.58 ng/mL; p < 0.001), CRP (4.9 vs. 1.5 mg/L; p < 0.001), IL-8 (6.00 vs. 4.58 pg/mL; p = 0.001), IL-10 (59.0 vs. 17.6 pg/mL; p = 0.007), and TNF-α (18.0 vs. 5.6 ng/mL; p < 0.001). In patients with raised baseline plasma IL-6/8/10 and/or PTX3 the eGFR decline during the trial was significantly less in those treated with atorvastatin compared to placebo (mean change, -3.36; vs. + 1.25 mL/min/1.73 m2/year; difference, 4.61 95% CI 0.98 - 8.25; p = 0.002), whilst those without raised inflammatory biomarkers showed no difference. Placebo treated patients with raised TNF-α levels had no eGFR decline (p > 0.90), whereas in atorvastatin-treated patients eGFR declined (p = 0.05). CONCLUSIONS: CKD patients with inflammation treated with atorvastatin had significantly less eGFR decline. Larger studies using statin therapy, specifically enrolling CKD patients with inflammation, may be worthwhile exploring.

The Association between Seasonal Variation in Vitamin D, Postural Sway, and Falls Risk: An Observational Cohort Study.

Introduction. Low serum vitamin D levels are associated with increased postural sway. Vitamin D varies seasonally. This study investigates whether postural sway varies seasonally and is associated with serum vitamin D and falls. Methods. In a longitudinal observational study, eighty-eight independently mobile community-dwelling older adults (69.7 ± 7.6 years) were evaluated on five occasions over one year, measuring postural sway (force platform), vitamin D levels, fall incidence, and causes and adverse outcomes. Mixed-methods Poisson regression was used to determine associations between measures. Results. Postural sway did not vary over the year. Vitamin D levels varied seasonally (P < 0.001), peaking in summer. Incidence of falls (P = 0.01) and injurious falls (P = 0.02) were lower in spring, with the highest fall rate at the end of autumn. Postural sway was not related to vitamin D (P = 0.87) or fall rates, but it was associated with fall injuries (IRR 1.59 (CI 1.14 to 2.24, P = 0.007). Conclusions. Postural sway remained stable across the year while vitamin D varied seasonally. Participants with high values for postural sway demonstrated higher rates of injurious falls. This study provides important evidence for clinicians and researchers providing interventions measuring balance outcomes across seasons.

Transcriptionally active human papillomavirus is strongly associated with Barrett's dysplasia and esophageal adenocarcinoma.

OBJECTIVES: The role of human papillomavirus (HPV) in Barrett's esophagus (BE) remains unclear. The few studies that have previously investigated HPV and esophageal adenocarcinoma (EAC) or BE have produced either negative data or positive results of doubtful clinical/etiological significance or have detected only low-risk HPV types. We therefore prospectively determined the prevalence of biologically active HPV in esophageal epithelium of patients representing the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. METHODS: HPV DNA was estimated by nested PCR and viral transcriptional activity detected by E6/7 oncogene mRNA expression and p16INK4A immunohistochemistry in fresh frozen and paraffin-embedded esophageal biopsies of patients with BE, Barrett's dysplasia (BD), and EAC, as well as controls. Biopsies were obtained from the transformation zone (squamocolumnar junction (SCJ)) and the lesion, or corresponding site in controls, i.e., 2 cm above the gastroesophageal junction (GEJ). RESULTS: Of the 261 patients, 81 were positive for HPV DNA. In controls and BE, the virus was mostly detected at the transformation zone. Compared with controls (18.0%), HPV positivity was significantly more common in BD (68.6%, incidence rate ratio (IRR) 2.94, 95% confidence interval (CI) 1.78-4.85, P<0.001) and EAC (66.7%, IRR 2.87, 95% CI 1.69-4.86, P<0.001), but not in BE (22.1%, IRR 1.06, 95% CI 0.60-1.85, P=0.85). Of the patients, 92.6% were high-risk (HR) HPV, i.e., types 16 and 18. Again, p16INK4A positivity was greatest in BD and EAC and much less in BE patients (44.1%, IRR 17.0 (95% CI 4.86-59.6, P<0.001), 44.4%, 17.0 (95% CI 4.87-59.4, P<0.001), and 10.6%, 3.93 (95% CI 1.01-15.3, P=0.048) respectively). In 66 HPV DNA-positive patients tested for E6/E7 mRNA, none of the control (n=16) or BE (n=13) individuals were positive, whereas 9/22 BD and 9/15 EAC patients demonstrated oncogene expression (P<0.001). When HPV DNA, p16INK4A, and E6/E7 mRNA were all positive, there was a very strong association with disease severity (SCJ: odds ratio (OR) 104, 95% CI 20.3-529, P<0.001; lesion: OR 62.2, 95% CI 12.4-311, P<0.001) than when all were negative. CONCLUSIONS: Transcriptionally active HR-HPV was strongly associated with BD and EAC, but was largely biologically irrelevant in BE and controls, suggesting a potential role in esophageal carcinogenesis. These data provide robust justification for further detailed longitudinal, interventional, and molecular studies.

Make vitamin D while the sun shines, take supplements when it doesn't: a longitudinal, observational study of older adults in Tasmania, Australia.

Low vitamin D status has been associated with a number of chronic conditions, particularly in older adults. The aim of this study was to identify how best to maintain optimum vitamin D status throughout the year in this high-risk population. The main objectives of the study were to assess seasonal vitamin D status; identify the main determinants of vitamin D status; determine if taking part in the study led to alterations in participant behaviour and vitamin D status. A longitudinal design across four consecutive seasons observed ninety-one 60-85 year old community-dwelling adults in Tasmania (41π S) over 13 consecutive months, with a follow-up assessment at next winter's end. Associations between solar UVB exposure, sun protection behaviours, dietary and supplemental vitamin D with serum 25(OH)D concentrations were assessed. Variation in serum 25(OH)D demonstrated an identical pattern to solar UVB, lagging 8-10 weeks. Serum 25(OH)D was positively associated with summer UVB (mean 15.9 nmol/L; 95%CI 11.8-19.9 nmol/L, p<0.001) and vitamin D supplementation (100-600 IU/day: 95%CI 10.2 nmol/L; 0.8-19.6 nmol/L; p = 0.03; 800 IU/day: 21.0 nmol/L; 95%CI 8.1-34.0 nmol/L; p = 0.001). Seasonal variation in serum 25(OH)D was greatly diminished in supplement users. The most common alteration in participant behaviour after the study was ingesting vitamin D supplements. Post-study vitamin D supplementation ℘800 IU/day was seven times more likely than during the study resulting in mean difference in serum 25(OH)D between supplement and non-supplement users of 30.1 nmol/L (95%CI 19.4-40.8 nmol/L; p<0.001). The main limitation was homogeneity of participant ethnicity. Solar exposure in summer and ingestion of vitamin D supplements in other seasons are the most effective ways of achieving and maintaining year-round vitamin D sufficiency in older adults in the Southern hemisphere. Vitamin D supplementation has greatest effect on vitamin D status if ingested during and after winter, i.e. between the autumn and spring equinoxes.

Development and experimental application of an HPLC procedure for the determination of capsaicin and dihydrocapsaicin in serum samples from human subjects.

Total capsaicins are extracted from 2 mL aliquots of serum or plasma using methyl-isobutyl ketone, evaporation of the extract to dryness and reconstitution with 200 µL of acetonitrile. The HPLC mobile phase is 40:60 water:acetonitrile. The absorbance of the eluent is monitored at 205 nm. Standardisation uses a known mixture of pure capsaicin and dihydrocapsaicin. Accuracies are 98.9 and 100.6 % for capsaicin and dihydrocapsaicin respectively. Inter batch reproducibility for both is 15 %. The limits of detection are 2.6 and 3.8 ng/mL for capsaicin and dihydrocapsaicin respectively. Analyses of sera obtained previously from human subjects who had eaten chilli containing meals showed that in those that absorbed capsaicins (N = 30) then the median, mean and SD of their serum capsaicin were: 13.4, 18.9 and 16.3 ng/mL. The corresponding data for those sera (N = 13) that had measurable levels of dihydrocapsaicin were: 6.9, 7.5 and 3.6 ng/mL. This procedure is suitable for use in prospective studies of the metabolism of orally ingested chilli.

Serum [25(OH)D] status, ankle strength and activity show seasonal variation in older adults: relevance for winter falls in higher latitudes.

BACKGROUND: seasonal variation exists in serum [25(OH)D] and physical activity, especially at higher latitudes, and these factors impact lower limb strength. This study investigates seasonal variation in leg strength in a longitudinal repeated measures design concurrently with serum vitamin D and physical activity. METHODS: eighty-eight community-dwelling independently mobile older adults (69.2 ± 6.5 years) were evaluated five times over a year, at the end of five consecutive seasons at latitude 41.1°S, recruited in two cohorts. Leg strength, serum [25(OH)D] and physical activity levels were measured. Time spent outside was recorded. Monthly falls diaries recorded falls. Data were analysed to determine annual means and percentage changes. RESULTS: significant variation in [25(OH)D] (±15%), physical activity (±13%), ankle dorsiflexion strength (±8%) and hours spent outside (±20%) (all P < 0.001) was demonstrated over the year, with maximums in January and February (mid-summer). Low mean ankle strength was associated with increased incidence of falling (P = 0.047). Quadriceps strength did not change (±2%; P = 0.53). CONCLUSION: ankle dorsiflexor strength varied seasonally. Increased ankle strength in summer may be influenced by increased levels of outdoors activity over the summer months. Reduced winter-time dorsiflexor strength may predispose older people to increased risk of tripping-related falls, and warrants investigation in a multi-faceted falls prevention programme.

Progressive resistance training might improve vascular function in older women but not in older men.

OBJECTIVES: Resistance exercise training increases strength and muscle mass in older adults however there is no consensus for its effect on arterial health. The aim of this study was to determine the effect of community based resistance training versus flexibility training on indicators of arterial stiffness and central blood pressure in healthy older adults and to test whether the effects of training are gender specific. DESIGN: A randomised crossover intervention study. METHODS: Forty-nine healthy elderly participants (23 males) aged 66.7±4.3 years (mean±SD) participated in this study which involved undertaking 16 weeks of resistance training and 16 weeks of flexibility training in a random order separated by a four week washout period of usual activity. Prior to and following each training protocol period, participants underwent testing of arterial stiffness as augmentation index; and central blood pressure. RESULTS: When all participants were compared no changes in any measure of arterial stiffness or central blood pressure following resistance training compared to flexibility training were found. When male and female participants were analysed separately, a statistically significant decrease in augmentation index was observed in females (-5.28%; 95% CI: -10.29 to -0.26; p=0.04) but not males (+1.72%; 95% CI: -3.04 to 6.48; p=0.48). CONCLUSIONS: Community based resistance exercise training does not adversely affect vascular function in apparently healthy older adults and may actually improve arterial function in females.

Effect of hereditary haemochromatosis genotypes and iron overload on other trace elements.

PURPOSE: Hereditary haemochromatosis is a common genetic disorder involving dysregulation of iron absorption. There is some evidence to suggest that abnormal iron absorption and metabolism may influence the status of other important trace elements. In this study, the effect of abnormal HFE genotypes and associated iron overload on the status of other trace elements was examined. METHODS: Dietary data and blood samples were collected from 199 subjects (mean age = 55.4 years; range = 21-81 years). Dietary intakes, serum selenium, copper and zinc concentrations and related antioxidant enzymes (glutathione peroxidase and superoxide dismutase) in subjects with normal HFE genotype (n = 118) were compared to those with abnormal HFE genotype, with both normal iron status (n = 42) and iron overload (n = 39). RESULTS: For most dietary and biochemical variables measured, there were no significant differences between study groups. Red cell GPx was significantly higher in male subjects with normal genotypes and normal iron status compared to those with abnormal genotypes and normal iron status (P = 0.03) or iron overload (P = 0.001). Red cell GPx was also highest in normal women and significantly lower in the abnormal genotype and normal iron group (P = 0.016), but not in the iron overload group (P = 0.078). CONCLUSION: Although it may not be possible to exclude a small effect between the genotype groups on RBC GPx, overall, haemochromatosis genotypes or iron overload did not appear to have a significant effect on selenium, copper or zinc status.

Relationship between antioxidant enzyme genotype and activity and kidney function: a case-control study.

BACKGROUND: Oxidative stress is associated with the progression of chronic kidney disease (CKD). Links between antioxidant enzyme SNPs such as superoxide dismutase (SOD) Ala16Val, glutathione peroxidase (GPx) Pro197Leu and catalase C- 262T and CKD have not been investigated. This study compared antioxidant genotypes and activities of CKD patients with population controls, and determined their relationship to kidney function. METHODS: CKD patients (n = 230) and controls (n = 224) were screened for the GPx, SOD and catalase SNPs. Plasma and red blood cell (RBC) GPx, RBC SOD and RBC catalase activities, and estimated glomerular filtration rate (eGFR) were measured. RESULTS: Significantly more CKD patients (n = 5) had the GPx Leu/Leu genotype compared to controls (n = 0), and had lower eGFR (p = 0.054). CKD patients had significantly lower plasma GPx and RBC catalase activities compared to controls, whereas RBC GPx and RBC SOD activities were significantly higher in CKD patients (p < 0.001). CONCLUSIONS: CKD is associated with reduced plasma GPx and catalase activities and enhanced RBC GPx and SOD activities. Although, genotype frequencies were similar for both groups, lower eGFR was associated with the GPx Leu/ Leu genotype.

Dietary selenium and major depression: a nested case-control study.

OBJECTIVES AND METHODS: Alterations in redox biology are established in depression; however, there are no prospective epidemiological data on redox-active selenium in depression. We aimed to determine if low levels of dietary selenium are associated with an increased risk for de novo major depressive disorder (MDD). In this nested case-control study, women aged 20 years or more were identified from a randomly selected cohort being followed prospectively for the Geelong Osteoporosis Study. Cases were individuals with incident MDD, identified using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP); controls had no such history. Dietary selenium intake was measured using a food frequency questionnaire at baseline, together with anthropometric and lifestyle measures. RESULTS: Eighteen women who developed de novo MDD were classified as cases; there were 298 controls. Low dietary selenium intakes increased the likelihood of developing MDD; OR 2.74 (95%CI 0.95-7.89). After adjusting for age and SES, compared with a high selenium intake, a low intake (<8.9 µg/MJ/day) was associated with an approximate trebling of the likelihood for developing de novo MDD; OR 2.95 (95%CI 1.00-8.72). Smoking, alcohol consumption and physical activity did not confound the association. CONCLUSION: These data suggest that lower dietary selenium intakes are associated with an increased risk of subsequent de novo MDD. We propose that selenium's function as an antioxidant, and as a constituent of selenoproteins that are important in redox homeostasis, warrants further investigation as a risk factor for depression, and suggest a potentially novel modifiable factor in the primary prevention and management of depression.

Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease.

The presence and progression of numerous diseases have been linked to deficiencies in antioxidant systems. The relationships between single nucleotide polymorphisms (SNPs) arising from specific antioxidant enzymes and diseases associated with elevated oxidative stress have been studied with the rationale that they may be useful in screening for diseases. The purpose of this narrative review is to analyse evidence from these studies. The antioxidant enzyme SNPs selected for analysis are based on those most frequently investigated in relation to diseases in humans: superoxide dismutase (SOD2) Ala16Val (80 studies), glutathione peroxidise (GPx1) Pro197Leu (24 studies) and catalase C-262T (22 studies). Although the majority of evidence supports associations between the SOD2 Ala16Val SNP and diseases such as breast, prostate and lung cancers, diabetes and cardiovascular disease, the presence of the SOD2 Ala16Val SNP confers only a small, clinically insignificant reduction (if any) in the risk of these diseases. Other diseases such as bladder cancer, liver disease, nervous system pathologies and asthma have not been consistently related to this SOD SNP genotype. The GPx1 Pro197Leu and catalase C-262T SNP genotypes have been associated with breast cancer, but only in a small number of studies. Thus, currently available evidence suggests antioxidant enzyme SNP genotypes are not useful for screening for diseases in humans.

Effects of atorvastatin on NGAL and cystatin C in chronic kidney disease: a post hoc analysis of the LORD trial.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C are biomarkers of kidney injury and function, respectively. This study assessed whether plasma NGAL and/or serum cystatin C predicted baseline estimated glomerular filtration rate (eGFR) and urinary protein excretion, rate of change of eGFR and urinary protein excretion and whether atorvastatin influenced changes in these biomarkers in patients with chronic kidney disease (CKD). METHODS: This is a post hoc analysis of the Lipid Lowering and Onset of Renal Disease trial, a randomized double-blind, placebo-controlled trial where 88 patients with Stages 2-4 CKD received atorvastatin 10 mg/day (48) or placebo (40). Stored blood samples were analysed for NGAL and cystatin C at baseline and a mean of 1.5 and 2.9 years later. Serum creatinine and Modification of Diet in Renal Disease (MDRD) eGFR were obtained three monthly. RESULTS: There were negative associations between NGAL and cystatin C and eGFR (P = 0.025 and P < 0.001, respectively) at all time points. There were no associations between baseline NGAL and cystatin C and rate of change of eGFR (P = 0.44 and P = 0.49, respectively). Baseline NGAL but not cystatin C (P = 0.043 and P = 0.35, respectively) predicted rate of change of urinary protein excretion. In atorvastatin-treated patients, NGAL decreased (mean, -7.4 ng/mL/year; SD 128.4), whereas it increased in the placebo group [mean, 4.6 ng/mL/year; SD 56.6), the difference being statistically significant (P = 0.049). CONCLUSIONS: NGAL is a biomarker of existing CKD but did not predict CKD progression. Atorvastatin reduced plasma NGAL but the significance and mechanisms require further investigation. Atorvastatin had no significant effect on cystatin C.

Marginal selenium status in northern Tasmania.

Se plays many important roles in humans. Marginal Se status has been associated with adverse health effects including an increased risk of chronic disease such as cancer. There are few Australian data, but the population of Tasmania, Australia, is potentially at risk of marginal Se status. A cross-sectional study of 498 men and women aged 25-84 years was undertaken to assess the Se status of the northern Tasmanian population. Se status was assessed using dietary estimates and measures of serum Se and glutathione peroxidase (GPx). Mean Se intakes were 77·4 (sd 31·3) and 65·1 (sd 23·7) µg/d for men and women, respectively; 27 % of the subjects consumed less than the Australian/New Zealand estimated average requirement. Mean serum Se concentration was 89·1 (sd 15·1) µg/l; 83 % of the study subjects had serum Se concentrations below 100 µg/l and 60 % had serum Se concentration below 90 µg/l, suggesting that Se status in many subjects was inadequate for maximal GPx activity. This was supported by the positive association between serum Se and serum GPx (P < 0·001), indicating that enzyme activity was limited by Se concentrations. The lowest mean serum Se concentrations were observed in the oldest age ranges; however, the prevalence of marginal Se status was similar across age ranges and did not appear to be influenced by sex or socio-economic status. The prevalence of marginal Se status was high in all sex and age subgroups, suggesting that the northern Tasmanian population could benefit from increasing Se intakes.

Cardiovascular and metabolic effects of community based resistance training in an older population.

Ageing is associated with decreases in strength and cardiovascular fitness, and increased cardiovascular risk factors. The aim of the current study was to determine the effectiveness of 16 weeks of community based resistance compared to flexibility training on strength, cardiovascular fitness and cardiovascular and metabolic parameters in a group of previously sedentary, healthy older men and women. A randomised controlled crossover intervention study. Forty nine healthy sedentary participants (23 males; age 66.7 ± 4.3 years; weight 78.6 ± 15.4 kg; mean ± SD) completed 16 weeks of supervised community-based resistance training and 16 weeks of flexibility training in a randomised order. Prior to and following each intervention, participants were assessed for muscle strength, cardiovascular fitness (VO(2 peak)), fasted blood lipids and blood glucose, insulin and insulin resistance. Resistance training resulted in significant increases in knee extension (+25.7 Nm; p < 0.001) and knee flexion strength (+8.9 Nm; p = 0.048) and decreases in fasting total cholesterol (-0.51 mmol L(-1); p = 0.001), HDL cholesterol (-0.12 mmol L(-1); p = 0.035), LDL cholesterol (-0.35 mmol L(-1); p = 0.022), glucose (-0.42 mmol L(-1); p < 0.001), insulin (-1.28 µU/mL; p = 0.049) and insulin resistance (-0.50 µU/mL; p = 0.004) compared to the flexibility protocol. No significant changes between the treatments were observed in VO(2peak) (+2.04 mL kg(-1)min(-1); p = 0.12). Community based resistance training is suitable for improving strength and reducing cardiovascular and metabolic risk factors in healthy older individuals.

Glutathione peroxidase, superoxide dismutase and catalase genotypes and activities and the progression of chronic kidney disease.

BACKGROUND: Oxidative stress has been linked to the progression of disease, including chronic kidney disease (CKD). The aim of the present study was to determine the association between single-nucleotide polymorphisms (SNPs) of the antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase and their activities and the progression of CKD. METHODS: This is a prospective cohort study of 185 CKD patients (Stages 2-4), followed for up to 12 months. All patients were genotyped for SNPs of SOD (SOD Ala16Val), GPx (GPx Pro197Leu) and catalase (C-262T). The rate of change over the study period of estimated glomerular filtration rate (eGFR), plasma and red blood cell (RBC) GPx, RBC SOD and RBC catalase activities were determined. RESULTS: CKD patients with the SOD Ala/Val and Val/Val genotypes had a significantly greater eGFR decline compared to those with the Ala/Ala genotype (Ala/Val compared with Ala/Ala odds ratio (OR) 0.35, 95% CI 0.19 to 0.64, P = 0.001; Val/Val compared with Ala/Ala OR 0.25, 95% CI 0.10 to 0.65, P = 0.005). The progression of CKD was not associated with SNPs of the GPx or catalase genes studied but there was a direct relationship between the rate of change of plasma GPx activity and the rate of change of eGFR over 12 months (P = 0.025). CONCLUSION: CKD patients with the SOD Ala/Val and Val/Val genotypes have a greater decline in kidney function than those with the Ala/Ala genotype.