Mitochondrial J haplogroup is associated with lower blood pressure and anti-oxidant status: findings in octo/nonagenarians from the BELFAST Study.

Mitochondria produce cellular energy but also free-radicals, which damage cells despite an array of endogenous anti-oxidants. In Northern Europe, the mitochondrial haplogroup J has been related to longevity in nonagenarians and centenarians but also with age-related disease. Hypertension is an important contributor to atherosclerotic-related diseases and its pathogenesis is associated with increased oxidative stress. In this study, we questioned whether J haplogroup octo/nonagenarians from the Belfast Elderly Longitudinal Free-living Elderly STudy (BELFAST) study showed evidence of protective blood pressure or anti-oxidant profile which might explain their longevity advantage. Briefly, in a cross-sectional study, community-living, mentally alert (Folstein >25/30), octo/nonagenarian subjects, recruited for good health, were enlisted and consented as part of the BELFAST study, for blood pressure, anthropometric measurements and blood sampling. DNA typing for mitochondrial haplotypes was carried out with measurements for enzymatic and non-enzymatic antioxidants. J haplogroup carriers showed lower systolic blood pressure and glutathione peroxidase activity (Gpx) with higher folate measurements. There was no change in urate, bilirubin, albumin or nutrition-related antioxidants-selenium or vitamins A, C and α and ß carotene. BELFAST study mtDNA J haplogroup octo/nonagenarians showed lower blood pressure and reduced glutathione peroxidase activity and higher folate, but no change for other antioxidants. These findings are of interest in view of mtDNA J haplogroup's association with increased age in some previous studies.

Indications of proton-dominated cosmic-ray composition above 1.6 EeV.

We report studies of ultrahigh-energy cosmic-ray composition via analysis of depth of air shower maximum (X(max)), for air shower events collected by the High-Resolution Fly's Eye (HiRes) observatory. The HiRes data are consistent with a constant elongation rate d/d[log(E)] of 47.9+/-6.0(stat)+/-3.2(syst) g/cm2/decade for energies between 1.6 and 63 EeV, and are consistent with a predominantly protonic composition of cosmic rays when interpreted via the QGSJET01 and QGSJET-II high-energy hadronic interaction models. These measurements constrain models in which the galactic-to-extragalactic transition is the cause of the energy spectrum ankle at 4x10(18) eV.

BELFAST centenarians: a case of optimised cardiovascular risk?

INTRODUCTION: Centenarians are reservoirs of genetic and environmental information to successful ageing and local centenarian groups may help us to understand some of these secrets. The current centenarian cohort in Belfast survived the 1970s epidemic of death from coronary heart disease in Northern Ireland, where cardiovascular mortality was almost highest in the world. These centenarians provided an opportunity to assess biological and genetic factors important in cardiovascular risk and ageing. METHODS: Thirty-five (27 female, 8 male) centenarians, participants of the Belfast Elderly Longitudinal Free-living Ageing STudy (BELFAST), were community-living and of good cognition at enrollment. RESULTS: Centenarians showed median Body Mass Index (BMI) at 25.7, systolic blood pressure 140 mmHg and diastolic blood pressure 90 mmHg respectively, and fasting glucose of 5.54 mmol/l with no sex-related difference. Lipoproteins showed median cholesterol 5.3, High Density Lipoprotein (HDL) 1.10 and Low Density Lipoprotein (LDL) 3.47 micromol/l respectively. Centenarian smokers showed no different blood pressure or lipid measurements compared with non-smokers. Malondialdehyde, a measure of lipid peroxidation, was low at 1.19, and measures of antioxidant status showed variable results. Male centenarians did not carry any of the vascular risk genotypes studied-Apolipoprotein E (ApoE), Angiotensin-Converting Enzyme (ACE) and Methylenetetrafolatedehydrogenase reductase (MTFHR), though this was not true for female centenarians. CONCLUSIONS: This small local study shows, apart from age, that Belfast centenarians carry a reasonably optimized risk profile with respect to cardiovascular disease. There is also some evidence suggesting that vascular risk factors and genotypes may be tolerated differently between the male and female centenarians. Maintaining an optimized cardiovascular risk profile seems likely to improve the chance of becoming a centenarian, especially for males.

Nature or nurture; BMI and blood pressure at 90. Findings from the Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST).

Hypertension is a key risk factor for stroke, cardiovascular disease and dementia. Although the link between weight, sodium and hypertension is established in younger people, little is known about their inter-relationship in people beyond 80 years of age. Associations between blood pressure, anthropometric indices and sodium were investigated in 495 apparently healthy, community-living participants (age 90, SD 4.8; range 80­106), from the cross-sectional Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST) study. In age-sex-adjusted logistic regression models, blood pressure ≥140/90 mmHg significantly associated with body mass index (BMI) [odds ratio (OR) = 1.28/ kg/m2], with weight (OR = 1.22/kg) approaching significance (P = 0.07). In further age-sex-adjusted models, blood pressure above the 120/80 mmHg normotensive reference value significantly associated with BMI (OR = 1.44/kg/m2), weight (OR = 1.36/kg), skin-fold-thickness (OR = 1.33/mm) and serum sodium (OR = 1.37 mmol/l). In BELFAST participants over 80 years old, blood pressure ≥140/90 mmHg is associated with BMI, in apparently similar ways to younger groups.

First observation of the Greisen-Zatsepin-Kuzmin suppression.

The High Resolution Fly's Eye (HiRes) experiment has observed the Greisen-Zatsepin-Kuzmin suppression (called the GZK cutoff) with a statistical significance of five standard deviations. HiRes' measurement of the flux of ultrahigh energy cosmic rays shows a sharp suppression at an energy of 6 x 10(19) eV, consistent with the expected cutoff energy. We observe the ankle of the cosmic-ray energy spectrum as well, at an energy of 4 x 10(18) eV. We describe the experiment, data collection, and analysis and estimate the systematic uncertainties. The results are presented and the calculation of the statistical significance of our observation is described.

Sodium measurement: effects of differing sampling and analytical methods.

BACKGROUND: It is recommended that children receiving intravenous fluids should have frequent biochemical monitoring, in some situations 4-6 hourly. Small changes in sodium must be detected, requiring very high precision from sodium analyses. Some children are monitored using venous blood analysed by indirect ion-selective electrode (ISE) interchangeably with capillary blood analysed by direct ISE. Our aim was to determine whether variability in sample collection together with variability in sodium measurement would lead to results which were unacceptable in the clinical setting. METHODS: Fifty-seven adults had capillary and venous blood analysed for sodium using direct ISE and venous plasma analysed for sodium using indirect ISE. RESULTS: Comparison of capillary blood analysed by direct ISE with venous plasma analysed by indirect ISE demonstrated wide scatter and poor correlation of results: r = 0.36, standard deviation (SD) of the differences 2.7 mmol/L and range of limits of agreement 10.6 mmol/L. Significant biases were observed comparing capillary blood sodium with venous plasma sodium (P < 0.001), and comparing direct ISE with indirect ISE (P < 0.001). CONCLUSIONS: Venous plasma using indirect ISE and capillary blood with direct ISE cannot be used interchangeably to detect small changes in plasma sodium concentrations. To avoid misinterpretation of results when monitoring sodium over short time periods, the use of single methods of sampling and analysis must be strongly encouraged.

Measurement of the flux of ultrahigh energy cosmic rays from monocular observations by the High Resolution Fly's Eye experiment.

We have measured the cosmic ray spectrum above 10(17.2) eV using the two air-fluorescence detectors of the High Resolution Fly's Eye observatory operating in monocular mode. We describe the detector, phototube, and atmospheric calibrations, as well as the analysis techniques for the two detectors. We fit the spectrum to a model consisting of galactic and extragalactic sources.

Dimercaptosuccinic acid loading test for assessing mercury burden in healthy individuals.

BACKGROUND: Oral chelation tests have been used to try to define mercury toxicity in individuals with dental amalgams, who are suffering from a variety of non-specific symptoms. METHODS: Self-reported healthy individuals volunteered to undergo an oral chelation test using dimercaptosuccinic acid (DMSA) at a dose of 30 mg/kg body weight. Urinary mercury : creatinine ratios were measured pre-dose and 3 h post-dose. RESULTS: Urinary mercury : creatinine ratios were similar to levels previously reported in individuals with symptoms that could have been attributed to mercury toxicity. One volunteer suffered a serious reaction to DMSA. CONCLUSION: The oral chelation test using DMSA may lead to misleading diagnostic advice regarding potential mercury toxicity and can be associated with serious side effects.

Genetics of the lipoprotein lipase gene and hypertriglyceridaemia.

The aim of this study is to assess whether genetic variation at the lipoprotein lipase (LPL) gene is related to fasting triglyceride levels or to the presence of vascular disease. Hypertriglyceridaemic patients are genotyped for the N291S, G188E, and P207L variants and the HindIII and PvuII restriction fragment length polymorphisms of the LPL gene. Sequence analysis is carried out on exons 1-9 of the LPL gene for patients with severe hypertriglyceridaemia, to search for new gene variants. No differences were found between the patient and control group for the N291S, G188E and P207L variants. The HindIII and PvuII allelic frequencies were found to be similar for patients and controls; however, the frequency of the PvuII P2 allele was higher in patients with vascular disease (allele frequency: 0.56) than patients with no vascular disease (allele frequency, 0.42) (P=0.03). Sequence analysis revealed no exon sequence variants in the LPL gene but two intron sequence variants were found in intron 5 in two patients.

Do the COL1A1 and Taq 1 vitamin D receptor polymorphisms have a role in identifying individuals at risk of developing osteoporosis?

The distribution of the Taq 1 polymorphism in the vitamin D receptor (VDR) gene and the MSc 1 polymorphism in the collagen 1 alpha 1 (COL1A1) gene were studied in 266 female and 55 male patients attending an osteoporosis clinic. Allele frequency in control (T- or Z-score >-1.0) and osteoporotic (T- or Z-scores <-2.5) groups were compared using Chi squared tests. No differences were found between the 2 groups with either of the polymorphisms. When allele frequency was compared in patients with and without history of fracture, no differences were found in the frequency of the COL1A1 alleles. However there were significantly more fracture patients, who had been previously treated with corticosteroids for other conditions, carrying the T allele of the VDR polymorphism (X2 = 5.65, p>0.01<0.02). In conclusion, neither of these polymorphisms aid in the prediction of osteoporosis but the VDRT allele may carry an increased fracture risk in patients who require corticosteroid treatment.

Serum mitochondrial aspartate transaminase activity after isoflurane or halothane anaesthesia.

We examined the effect of halothane or isoflurane anaesthesia on hepatic function in 30 ASA I-III patients aged 18-70 yr undergoing lumbar discectomy. Hepatic function was assessed before anaesthesia, at the end of surgery, and at 3, 6, 24 and 48 h after surgery using routine enzyme tests of hepatic function and mitochondrial aspartate transaminase (mAST) activity. Although serum mAST activities increased after surgery in both groups of patients, these increases were statistically significantly greater in the group that received halothane. The groups were similar with regard to other tests of hepatic function. Calculation of the ratio of serum enzyme activities compared to baseline values suggested that mAST is a sensitive marker of anaesthetic-induced hepatic injury.

Community-living nonagenarians in northern ireland have lower plasma homocysteine but similar methylenetetrahydrofolate reductase thermolabile genotype prevalence compared to 70-89-year-old subjects.

This cross-sectional study assessed relationships between plasma homocysteine, 'thermolabile' methylenetetrahydrofolatereductase (MTHFR) genotype, B vitamin status and measures of renal function in elderly (70-89 years) and nonagenarian (90+ years) subjects, with the hypothesis that octo/nonagenarian subjects who remain healthy into old age as defined by 'Senieur' status might show reduced genetic or environmental risk factors usually associated with hyperhomocysteinaemia. Plasma homocysteine was 9.1 micromol/l (geometric mean [GM]) for all elderly subjects. Intriguingly, homocysteine was significantly lower in 90+ (GM; 8.2 micromol/l) compared to 70-89-year-old subjects (GM; 9.8 micromol/l) despite significantly lower glomerular filtration rate (GFR) and serum B12 in nonagenarian subjects and comparable MTHFR thermolabile (TT) genotype frequency, folate and B6 status to 70-89-year-olds. For all elderly subjects, the odds ratio and 95% confidence intervals for plasma homocysteine being in the highest versus lowest quartile was 4.27 (2.04-8.92) for age <90 compared >90 years, 3.4 (1.5-7.8) for serum folate <10.7 compared >10.7nmol/l, 3.0 (0.9-10.2) for creatinine >140 compared <140 umol/l and 2.1 (1.0-4.4) for male sex. This study shows that plasma homocysteine does not invariably increase with age. Compared to similarly enlisted 70-89-year-olds, apparently well, mentally alert, community-living 90+ year olds approximating 'Senieur' status, show lower homocysteine, which is unexplained by renal function, TT genotype and B vitamin status, suggesting that lower homocysteine may be associated with survival.

Misleading serum free thyroxine results during low molecular weight heparin treatment.

Measured free thyroxine concentrations in serum increase markedly after intravenous heparin administration, but the effect of heparin administered subcutaneously has not been adequately documented. We found in vitro increases of up to 63% in measured FT4 after a single dose of subcutaneous heparin (enoxaparin, 2000 units) in nine healthy volunteers, and the magnitude of these increases was correlated with initial serum triglyceride concentrations (r = 0.93, P <0.005) and in vitro free fatty acid release (r = 0.88, P <0.005). In 10 cardiac inpatients receiving repeated doses of enoxaparin (2000 units twice daily), measured FT4 increased by up to 171% in specimens taken 2-6 h after injection. When specimens were obtained 10 h after injection, the effect appeared to be minimized, with in vitro increases of <40%, but such increases may still be sufficient to cause interpretative errors. If FT4 estimation is absolutely necessary in patients receiving enoxaparin, specimens should be taken > or =10 h postdose and analyzed within 24 h.

Effect of low to moderate levels of smoking and alcohol consumption on serum immunoglobulin concentrations.

AIM: To determine the effect of low to moderate levels of smoking and alcohol consumption on immunoglobulin concentrations. METHODS: Serum samples from 1787 subjects with approximately equal numbers in each five year group from 15 to 64 years were obtained from a large random population survey in Northern Ireland. Details were available on each subject concerning the number of units of alcohol consumed per week and the number of cigarettes smoked per day. IgG, IgM, and IgA concentrations were measured by laser nephelometry on all serum samples. RESULTS: Low to moderate consumption of alcohol was associated with a decrease in IgG and IgM median concentrations in contrast to an increase in IgA median concentrations. The decrease in IgM and especially IgG median concentrations appeared to be related to the smoking habits of the subjects. Alcohol consumption alone was associated with increased IgA median concentrations whereas cigarette smoking alone was associated with reduced IgG median concentrations. CONCLUSION: Low levels of alcohol consumption and cigarette smoking influence IgG, IgM, and IgA serum concentrations. This should be borne in mind when selecting subjects for use in research and clinical settings.

Plasma ubiquinol/cholesterol ratios in patients with hyperlipidaemia, those with diabetes mellitus and in patients requiring dialysis.

Plasma ubiquinol was measured in diabetics, patients on haemodialysis (HD) therapy, patients maintained by continuous ambulatory peritoneal dialysis (CAPD), hyperlipidaemic patients and control subjects. Ubiquinol values were standardized using total cholesterol (mumol/mmol). Diabetics, HD and CAPD patients were found to have plasma ubiquinol levels which were lower than the control subjects. There was no difference in values between the control subjects and hyperlipidaemic patients. Values for diabetics with poor metabolic control were similar to those with good control, and patients with diabetic complications had values which were not significantly different from those for patients with no complications. IDDM patients were found to have values which were lower than the control group, whereas values for the NIDDM patients were not significantly different. These results suggest that increased oxidative stress in certain patient groups may be the result of, and/or the cause of, decreased plasma ubiquinol. This could be due to increased demand or to decreased ability to regenerate the effective form of antioxidant.

Biochemical markers of alcohol abuse.

Excessive alcohol consumption is a major health problem in the UK leading to both serious morbidity and mortality. This study compared newer potential biochemical markers of excessive alcohol consumption [carbohydrate-deficient transferrin (CDT), mitochondrial AST (mAST) and alpha glutathione-s-transferase (alpha-GST)] with conventional markers (AST, ALT, GGT, MCV). Patients (n = 85) were enrolled in the study and subdivided into several groups on the basis of alcohol consumption. Patients with non-alcoholic liver disease (NALD) (n = 40) were also enrolled. All the markers, with the exception of the ratio mAST/total AST were significantly higher in heavy drinkers/alcoholics compared to teetotallers/social drinkers (p < 0.05). mAST and AST/ALT ratio were significantly higher in alcoholics compared to NALD (p < 0.01), whereas ALT was higher in the NALD group (p < 0.05). Multivariate discriminant function analysis (Wilks method) demonstrated that the logarithmic functions of AST/ALT ratio and mAST could correctly classify 87.9% of cases into either the alcoholic or NALD groups. ROC plot analysis showed that AST, mAST and GGT were the best markers at distinguishing heavy consumption of alcohol from lesser levels and that AST/ALT ratio and mAST were the best in distinguishing alcoholics from NALD. In conclusion, none of the newer biochemical markers, with the exception of mAST, offers any major advantage over the conventional markers.