Effects of a Two-Year Home-Based Exercise Training Program on Oxidized LDL and HDL Lipids in Coronary Artery Disease Patients with and without Type-2 Diabetes

We investigated the effect of two-year home-based exercise training program on oxidized low-density lipoprotein LDL (ox-LDL) and high-density lipoprotein HDL (ox-HDL) lipids in patients with coronary artery disease (CAD), both with and without type-2 diabetes (T2D). Analysis of lipoprotein-oxidized lipids was based on the determination of baseline conjugated dienes in lipoprotein lipids. In order to study the effect of an exercise load on ox-LDL and ox-HDL lipids patients in both CAD and CAD + T2D intervention, groups were divided in three based on exercise load (high, medium, and low). During the two-year home-based exercise training program, the study showed that only higher training volume resulted in a decreased concentration of ox-LDL, while the two groups with lower training volumes showed no change. This result indicates that the training load needs to be sufficiently high in order to decrease the concentration of atherogenic ox-LDL lipids in patients with CAD and CAD + T2D. Interestingly, the concentration of ox-HDL did not change in any of the subgroups. This could indicate that the lipid peroxide-transporting capacity of HDL, suggested by results from exercise training studies in healthy adults, may not function similarly in CAD patients with or without T2D. Moreover, the lipid-lowering medication used may have had an influence on these results

Circulating cell-free DNA level predicts all-cause mortality independent of other predictors in the Health 2000 survey

Increased levels of circulating cell-free DNA (cf-DNA) are associated with and predict poor health outcomes. However, its predictive ability for mortality in population-based samples remains understudied. We analysed the capability of cf-DNA to predict all-cause mortality and assessed whether it adds predictive value on top of the other risk factors in the Health 2000 survey (n = 1,257, 46-76 years of age, 15-years-follow-up, 18% deceased). When analysed in a multivariate model with the other factors that independently predicted mortality in the sample (age, gender, self-rated health, smoking and plasma levels of glucose and adiponectin), increases in cf-DNA levels were associated with increased risk of mortality (hazard ratio [HR] for 0.1 mu g increase in cf-DNA: 1.017, 95% confidence interval [CI] 1.008-1.026, p = 0.0003). Inclusion of cf-DNA in the model improved the model fit and discrimination. Stratifying the analysis by cardiovascular disease (CVD) status indicated that cf-DNA predicted mortality equally well in individuals with (HR 1.018, 95% CI 1.008-1.026, p = 0.002) and without (HR 1.018, 95% CI 1.001-1.035, p = 0.033) CVD. In conclusion, our study indicates that cf-DNA level predicts mortality in middle-aged and older individuals, also among those with established CVD, and adds significant value to mortality prediction. Our results thus underscore the role of cf-DNA as a viable marker of health

Risk factors for major adverse cardiovascular events after the first acute coronary syndrome

AimsTo evaluate risk factors for major adverse cardiac event (MACE) after the first acute coronary syndrome (ACS) and to examine the prevalence of risk factors in post-ACS patients.MethodsWe used Finnish population-based myocardial infarction register, FINAMI, data from years 1993-2011 to identify survivors of first ACS (n = 12686), who were then followed up for recurrent events and all-cause mortality for three years. Finnish FINRISK risk factor surveys were used to determine the prevalence of risk factors (smoking, hyperlipidaemia, diabetes and blood pressure) in post-ACS patients (n = 199).ResultsOf the first ACS survivors, 48.4% had MACE within three years of their primary event, 17.0% were fatal. Diabetes (p = 4.4 x 10(-7)), heart failure (HF) during the first ACS attack hospitalization (p = 6.8 x 10(-15)), higher Charlson index (p = 1.56 x 10(-19)) and older age (p = .026) were associated with elevated risk for MACE in the three-year follow-up, and revascularization (p = .0036) was associated with reduced risk. Risk factor analyses showed that 23% of ACS survivors continued smoking and cholesterol levels were still high (>5mmol/l) in 24% although 86% of the patients were taking lipid lowering medication.ConclusionDiabetes, higher Charlson index and HF are the most important risk factors of MACE after the first ACS. Cardiovascular risk factor levels were still high among survivors of first ACS

HMG1A and PPARG are differently expressed in the liver of fat and lean broilers

The expression of nine functional candidates for QT abdominal fat weight and relative abdominal fat content was investigated by real-time polymerase chain reaction (PCR) in the liver, adipose tissue, colon, muscle, pituitary gland and brain of broilers. The high mobility group AT-hook 1 (HMG1A) gene was up-regulated in liver with a ratio of means of 2.90 (P ≤ 0.01) in the «fatty» group (relative abdominal fat content 3.5 ± 0.18%, abdominal fat weight 35.4 ± 6.09 g) relative to the «lean» group (relative abdominal fat content 1.9 ± 0.56%, abdominal fat weight 19.2 ± 5.06 g). Expression of this gene was highly correlated with the relative abdominal fat content (0.70, P ≤ 0.01) and abdominal fat weight (0.70, P ≤ 0.01). The peroxisome proliferator-activated receptor gamma (PPARG) gene was also up-regulated in the liver with a ratio of means of 3.34 (P ≤ 0.01) in the «fatty» group relative to the «lean» group. Correlation of its expression was significant with both the relative abdominal fat content (0.55, P ≤ 0.05) and the abdominal fat weight (0.57, P ≤ 0.01). These data suggest that the HMG1A and PPARG genes were candidate genes for abdominal fat deposition in chickens. Searching of rSNPs in regulatory regions of the HMG1A and PPARG genes could provide a tool for gene-assisted selection

Quantification of the energy gap in young overweight children. The PIAMA birth cohort study

Background: Overweight develops gradually as a result of a long term surplus on the balance between energy intake and energy expenditure. Aim of this study was to quantify the positive energy balance responsible for excess body weight gain (energy gap) in young overweight children. Methods. Reported data on weight and height were used of 2190 Dutch children participating in the PIAMA birth cohort study. Accumulated body energy was estimated from the weight gain observed between age 2 and age 5-7. Energy gap was calculated as the difference in positive energy balance between children with and without overweight assuming an energy efficiency of 50%. Results: Ten percent of the children were overweight at the age of 5-7 years. For these children, median weight gain during 4-years follow-up was 13.3 kg, as compared to 8.5 kg in the group of children who had a normal weight at the end of the study. A daily energy gap of 289-320 kJ (69-77 kcal) was responsible for the excess weight gain or weight maintenance in the majority of the children who were overweight at the age of 5-7 years. The increase in daily energy requirement to maintain the 4.8 kilograms excess weight gain among overweight children at the end of the study was approximately 1371 kJ. Conclusions: An energy gap of about 289-320 kJ per day over a number of years can make the difference between normal weight and overweight in young children. Closing the energy gap in overweight children can be achieved by r

GU81, a VEGFR2 antagonist peptoid, enhances the anti-tumor activity of doxorubicin in the murine MMTV-PyMT transgenic model of breast cancer

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial growth factor (VEGF) is a primary stimulant of angiogenesis under physiological and pathological conditions. Anti-VEGF therapy is a clinically proven strategy for the treatment of a variety of cancers including colon, breast, lung, and renal cell carcinoma. Since VEGFR2 is the dominant angiogenic signaling receptor, it has become an important target in the development of novel anti-angiogenic therapies. We have reported previously the development of an antagonistic VEGFR2 peptoid (GU40C4) that has promising anti-angiogenic activity <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>In the current study, we utilize a derivative of GU40C4, termed GU81 in therapy studies. GU81 was tested alone or in combination with doxorubicin for <it>in vivo </it>efficacy in the MMTV-PyMT transgenic model of breast cancer.</p> <p>Results</p> <p>The derivative GU81 has increased <it>in vitro </it>efficacy compared to GU40C4. Single agent therapy (doxorubicin or GU81 alone) had no effect on tumor weight, histology, tumor fat content, or tumor growth index. However, GU81 is able to significantly to reduce total vascular area as a single agent. GU81 used in combination with doxorubicin significantly reduced tumor weight and growth index compared to all other treatment groups. Furthermore, treatment with combination therapy significantly arrested tumor progression at the premalignant stage, resulting in increased tumor fat content. Interestingly, treatment with GU81 alone increased tumor-VEGF levels and macrophage infiltration, an effect that was abrogated when used in combination with doxorubicin.</p> <p>Conclusion</p> <p>This study demonstrates the VEGFR2 antagonist peptoid, GU81, enhances the anti-tumor activity of doxorubicin in spontaneous murine MMTV-PyMT breast tumors.</p

Dietary carotenoid-rich oil supplementation improves exercise-induced anisocytosis in runners: influences of haptoglobin, MnSOD (Val9Ala), CAT (21A/T) and GPX1 (Pro198Leu) gene polymorphisms in dilutional pseudoanemia (sports anemia)

Physical training induces beneficial adaptation, whereas exhaustive exercises increase reactive oxygen-species generation, thereby causing oxidative damage in plasma and erythrocytes, fractions susceptible to lipid peroxidation. Pequi (Caryocar brasiliense Camb.) is a Brazilian Cerrado fruit containing a carotenoid-rich oil. The aim was to investigate the effects of pequi-oil on exercise-induced oxidative damage in plasma and erythrocytes, after running in the same environment and undergoing weekly training under the same conditions as to type, intensity and length. Evaluations were accomplished after outdoor running on flat land before and after ingestion of 400 mg pequi-oil capsules for 14 days. Blood samples were taken after running and submitted to TBARS assay and erythrogram analysis. Haptoglobin, MnSOD (Val9Ala), CAT (21A/T) and GPX1 (Pro198Leu) gene polymorphisms were priorly investigated, so as to estimate genetic influence The reduction in erythrocytes, hemoglobin and hematocrit after pequi-oil treatment was notably associated with higher plasma expansion. Except for MCHC (mean corpuscular hemoglobin concentration) and RDW (red cell distribution width), the results were influenced by the polymorphisms studied. The best response to pequi-oil was presented by MnSOD Val/Val, CAT AA or AT genotypes and the GPX1 Pro allele. The significantly lower RDW and higher MHCH values were related to pequi-oil protective effects. Pequi oil, besides possessing other nutritional properties, showed protective blood effects

Effects of therapy with [177Lu-DOTA0,Tyr3]octreotate on endocrine function

Purpose: Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues is a novel therapy for patients with somatostatin receptor-positive tumours. We determined the effects of PRRT with [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate) on glucose homeostasis and the pituitary-gonadal, pituitary-thyroid and pituitary-adrenal axes. Methods: Hormone levels were measured and adrenal function assessed at baseline and up to 24 months of follow-up. Results: In 35 men, mean serum inhibin B levels were decreased at 3 months post-therapy (205 ± 16 to 25 ± 4 ng/l, p 550 nmol/l, n = 18). Five patients developed elevated HbA1clevels (> 6.5%). Conclusion: In men177Lu-octreotate therapy induced transient inhibitory effects on spermatogenesis, but non-SHBG-bound T levels remained unaffected. In the long term, gonadotropin levels decreased significantly in postmenopausal women. Only a few patients developed hypothyroidism or elevated levels of HbA1c. Therefore, PRRT with177Lu-octreotate can be regarded as a safe treatment modality with respect to short-and long-term endocrine function

Gene polymorphisms of superoxide dismutases and catalase in diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Reactive oxygen species generated by hyperglycaemia modify structure and function of lipids, proteins and other molecules taking part in chronic vascular changes in diabetes mellitus (DM). Low activity of scavenger enzymes has been observed in patients with DM. Protective role of scavenger enzymes may be deteriorated by oxidative stress. This study was undertaken to investigate the association between gene polymorphisms of selected antioxidant enzymes and vascular complications of DM.</p> <p>Results</p> <p>Significant differences in allele and genotype distribution among T1DM, T2DM and control persons were found in SOD1 and SOD2 genes but not in CAT gene (p < 0,01). Serum SOD activity was significantly decreased in T1DM and T2DM subjects compared to the control subjects (p < 0,05). SOD1 and SOD2 polymorphisms may affect SOD activity. Serum SOD activity was higher in CC than in TT genotype of SOD2 gene (p < 0,05) and higher in AA than in CC genotype of SOD1 gene (p < 0,05). Better diabetes control was found in patients with CC than with TT genotype of SOD2 gene. Significantly different allele and genotype frequencies of SOD2 gene polymorphism were found among diabetic patients with macroangiopathy and those without it. No difference was associated with microangiopathy in all studied genes.</p> <p>Conclusion</p> <p>The results of our study demonstrate that oxidative stress in DM can be accelerated not only due to increased production of ROS caused by hyperglycaemia but also by reduced ability of antioxidant defense system caused at least partly by SNPs of some scavenger enzymes.</p