Metformin is the first line therapy of type 2 diabetics, but continued reduction of their life expectancy warrants further investigation into alternative treatment strategies. This study reports on the combinational use of metformin with aspalathin, a C-glucosyl dihydrochalcone with known glucose lowering and antioxidant properties, as an effective hypoglycemic therapy in a type 2 diabetic (db/db) mouse model. When tested as a monotherapy, a low dose of aspalathin (13 mg/kg) showed no effect, while a high dose (130 mg/kg) has already displayed a better potential than metformin in protecting against diabetes associated symptoms in db/db mice. Thus, it remains of interest to determine whether this dihydrochalcone can improve the efficacy of metformin. The results showed that this combination therapy was more effective than the use of metformin as a monotherapy in ameliorating diabetes associated symptoms, including abnormal raised fasting plasma glucose levels, impaired glucose tolerance, as well as excessively increased body weights and fat content. The treated mice also had reduced food and water consumption when compared to untreated controls, with a pronounced effect evident in the last week of treatment. Therefore, this study supports further investigations into the ameliorative effect of combination therapy of metformin and aspalathin against diabetes associated symptoms., P. V. Dludla, K. B. Gabuza, C. J. F. Muller, E. Joubert, J. Louw, R. Johnson., and Obsahuje bibliografii
Increased parasympathetic tone achieved with endurance training may provide cardioprotection after menopause. To compare heart rate variability (HRV) from rest through maximal exercise and recovery in trained postmenopausal women. Thirtysix postmenopausal women who self-reported training at either moderate (MOD; 3-5.9 METS; 58.9±4.4 year) or vigorous (VIG; >6 METS; 59.7±5.2 year) intensities participated. HRV was measured for 5 min in the supine position, in the last minute of the VO2max test and after 2 min of active recovery. HRV in MOD and VIG was compared using a factorial ANOVA with repeated measures on time. MOD and VIG responded similarly over the three time periods for root mean square of sequential deviations (rMSSD), and high (HF) and low frequency (LF) power (p>0.05). Maximal exercise lowered rMSSD (3.3±0.08 vs. 1.2±0.06) and lnLF (4.1±0.05 vs. 3.3±0.13) and increased lnHF (3.3±0.14 vs. 4.0±0.10; p<0.01) from resting. However, active recovery restored lnHF (3.3±0.11) and lnLF (4.1±0.08) from maximal values (p<0.01). Our findings suggest that moderate and vigorous exercise training may enhance HRV recovery following one bout of maximal exercise in older women., J. C. Orri, E. M. Hughes, D. G. Mistry, A. Scala., and Obsahuje bibliografii
Dyslipidemia is the risk fact or of cardiovascular disease, but the relationship between the plasma triglyceride (TG) levels and total/cardiovascular mortality has not yet been analy zed in Slavs. The aim of our study was to analy ze the association between the fasting TG levels and all- cause/cardiovascular mortality. We have examined 3,143 males and 3,650 females, aged 58.3±7.1 years. 729 deaths (274 cardiovascular deaths) have been registered during up to 11.8 years of follow -up. Age -sex adjusted all -cause mortality was higher in individuals with TG values 3.01 -4.00 mmol /l (HR 1.37, 95 % CI 1.02- 1.83, P=0.035) and over 4.00 mmol /l (HR 1.66, 95 % CI 1.21 -2.27, P=0.002) when compared with a reference group (TG 1.41 -1.80 mmol /l). Elevated risk remains significant when adjusted for education, marital status and unemployment. When further adjusted for smoking, BMI and dyslipidemia interventions, HR for those in above 4.00 mmol/l group decreas ed (1.42, P=0.04). The results have been similar when cardiovascular mortality has been examined, however, results reached statistical significance only for the TG over 4.0 mmol /l (P=0.028). Our results confirmed that enhanced plasma levels of plasma triglycerides are dose dependently associated with increased risk of all- cause mortality, however, it s eems that individuals with TG values 1.8 -3.0 mmol /l are not in higher risk of death., H. Pikhart, J. A. Hubáček, A. Peasey, R. Kubínová, M. Bobák., and Obsahuje bibliografii
Both, common gene variants and human adenovirus 36 (Adv36) are involved in the pathogenesis of obesity. The potential relationship between these two pathogenic factors has not yet been investigated. The aim of our study was to examine the association of obesity susceptibility loci with Adv36 status. Genotyping of ten gene variants (in/near TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, FTO) and analysis of Adv36 antibodies was performed in 1,027 Czech adolescents aged 13.0-17.9 years. Variants of two genes (PCSK1 and BDNF) were associated with Adv36 seropositivity. A higher prevalence of Adv36 antibody positivity was observed in obesity risk allele carriers of PCSK1 rs6232, rs6235 and BDNF rs4923461 vs. noncarriers (χ2=6.59, p=0.010; χ2=7.56, p=0.023 and χ2=6.84, p=0.033, respectively). The increased risk of Adv36 positivity was also found in PCSK1 variants: rs6232 (OR=1.67, 95 % CI 1.11-2.49, p=0.016) and rs6235 (OR=1.34, 95 % CI 1.08-1.67, p=0.010). PCSK1 rs6232 and BDNF rs925946 variants were closely associated with Adv36 status in boys and girls, respectively (χ2=5.09, p=0.024; χ2=7.29, p=0.026). Furthermore, PCSK1 rs6235 risk allele was related to Adv36 seropositivity (χ2=6.85, p=0.033) in overweight/obese subgroup. In conclusion, our results suggest that obesity risk variants of PCSK1 and BDNF genes may be related to Adv36 infection., L. Dušátková, H. Zamrazilová, I. Aldhoon Hainerová, R. L. Atkinson, B. Sedláčková, Z. P. Lee, J. Včelák, B. Bendlová, M. Kunešová, V. Hainer., and Obsahuje bibliografii
Present study aimed to explore the levels and correlation of oxidative stress biomarkers with anthropometry in a population of young Saudi females. One hundred six normotensives, non-diabetic Saudi females, with minimally active lifestyle, based on their body mass index (BMI) were divided as; normal-weight (NW; n=52), overweight (OW; n=24) and obese (OB; n=30). Anthropometric measurements [BMI, Waist Circumference (WC), Waist-Hip Ratio (WHR), Body Density (BD), Body Adiposity Index (BAI), % Body fat] and oxidative stress biomarkers; Thiobarbituric acid reactive substances (TBARS), 8-hydroxy-2- deoxyguanosine (8-OH-2dG: indicative of DNA/RNA damage), Superoxide dismutase, Serum total antioxidant capacity) were recorded. There was statistically significant higher 8-OH-2dG (pg/ml) in OB compared to NW (800.63±6.19 vs. 780.22±3.34; p=0.007), as determined by one-way ANOVA and Tukey post hoc test. 8-OH-2dG was significantly and positively associated with BMI (r=0.286, p=0.004), WC (r=0.280, p=0.005), BAI (r=0.26, p=0.008), and % body fat (r=0.27, p=0.006). There may be significantly increased DNA damage in normoglycemic, normotensive obese adolescent females. This can be linked to the amount of adipose tissue in the body as depicted by strong positive association between DNA damage and BMI, WC, BAI, and % body fat., R. Latif, N. Rafique., and Obsahuje bibliografii
The subclass of triglyceride -rich lipoproteins - remnant -like particles (RLP) seems to be strong and independent risk factor for cardiovascular disease. We eva luated the role of RLP and other risk factors (RF) with sonographically measured intima - media thickness of carotid arteries (IMT CCA) in a cohort of Czech population including women defined according to the time after menopause. We investigated relation of IMT CCA to age, weight, central obesity, plasma lipids including remnant -like particles cholesterol (RLP -C) and triglycerides (RLP -TG) in 136 men and 160 women. Using multiple linear regression analysis, significant association between IMT CCA and RLP -C was found in women 1 -7 years after menopause. In the whole group of women, only age and fasting blood glucose were independently associated with IMT CCA. In men only age significantly correlated wit h IMT CCA. Significant decrease of all plasma lipids betwe en 1988 and 1996 in men was detected, while in women significant increase in triglycerides and no change in non -HDL cholesterol was observed. RLP -C was the strongest independent RF for atherosclerosis in postmenopausal women but its as sociation with IMT CC A was limited to several years after menopause. In conclusion, women changing reproductive status could be more sensitive to atherogenic impact of remnant lipoproteins., J. Piťha, J. Kovář, Z. Škodová, R. Cífková, P. Stávek, L. Červenka, T. Šejda, V. Lánská, R. Poledne., and Obsahuje bibliografii
Obesity in childhood increases the risk of obesity in adulthood and is predictive for the development of metabolic disorders. The fatty acid composition is associated with obesity and obesityassociated disorders. We investigated the relationship between serum fatty acids composition, adiposity, lipids profile, parameters of glucose metabolism and leptin. The study subjects were 380 adolescents aged 15.0-17.9 years. The study's variables included anthropometric measurements, levels of serum lipids and hormonal parameters. Individual fatty acids were determined in plasma by gas-liquid chromatography. Palmitoleic acid (16:1n-7, PA) significantly positively correlated with percentage of body fat. Saturated fatty acids in phospholipids (PL) positively correlated with BMI and percentage of body fat. PA content in all lipids classes positively correlated with total cholesterol (TC), HDL cholesterol, triglycerides (TG) levels. Stearoyl-CoA desaturase (SCD) activity positively correlated with percentage of body fat and positive correlations of SCD and PA level with leptin were found. Plasma PA content and SCD are associated with adiposity and leptin in obese adolescents. No significant correlation between PA level and insulin resistance was found. Palmitoleate positively correlated with TC, HDL cholesterol, TG and LDL cholesterol levels., P. Hlavaty, E. Tvrzicka, B. Stankova, H. Zamrazilova, B. Sedlackova, L. Dusatkova, V. Hainer, M. Kunesova., and Obsahuje bibliografii
The atherogenic impact and functional capacity of LCAT was studied and discussed over a half century. This review aims to clarify the key points that may affect the final decision on whether LCAT is an anti-atherogenic or atherogenic factor. There are three main processes involving the efflux of free cholesterol from peripheral cells, LCAT action in intravascular pool where cholesterol esterification rate is under the control of HDL, LDL and VLDL subpopulations, and finally the destination of newly produced cholesteryl esters either to the catabolism in liver or to a futile cycle with apoB lipoproteins. The functionality of LCAT substantially depends on its mass together with the composition of the phospholipid bilayer as well as the saturation and the length of fatty acyls and other effectors about which we know yet nothing. Over the years, LCAT puzzle has been significantly supplemented but yet not so satisfactory as to enable how to manipulate LCAT in order to prevent cardiometabolic events. It reminds the butterfly effect when only a moderate change in the process of transformation free cholesterol to cholesteryl esters may cause a crucial turn in the intended target. On the other hand, two biomarkers - FERHDL (fractional esterification rate in HDL) and AIP [log(TG/HDL-C)] can offer a benefit to identify the risk of cardiovascular disease (CVD). They both reflect the rate of cholesterol esterification by LCAT and the composition of lipoprotein subpopulations that controls this rate. In clinical practice, AIP can be calculated from the routine lipid profile with help of AIP calculator www.biomed.cas.cz/fgu/aip/calculator.php., M. Dobiášová., and Obsahuje bibliografii
Each cell types or tissues contain certain “physiological” levels of R-2-hydroxyglutarate (2HG), as well as enzymes for its synthesis and degradation. 2HG accumulates in certain tumors, possessing heterozygous point mutations of isocitrate dehydrogenases IDH1 (cytosolic) or IDH2 (mitochondrial) and contributes to strengthening their malignancy by inhibiting 2-oxoglutaratedependent dioxygenases. By blocking histone de-methylation and 5-methyl-cytosine hydroxylation, 2HG maintains cancer cells de-differentiated and promotes their proliferation. However, physiological 2HG formation and formation by non-mutant IDH1/2 in cancer cells were neglected. Consequently, low levels of 2HG might play certain physiological roles. We aimed to elucidate this issue and found that compared to highest 2HG levels in hepatocellular carcinoma HepG2 cells and moderate levels in neuroblastoma SH-SY5Y cells, rat primary fibroblast contained low basal 2HG levels at early passages. These levels increased at late passage and likewise 2HG/2OG ratios dropped without growth factors and enormously increased at hypoxia, reaching levels compared to cancer HepG2 cells. Responses in SH-SY5Y cells were opposite. Moreover, external 2HG supplementation enhanced fibroblast growth. Hence, we conclude that low 2HG levels facilitate cell proliferation in primary fibroblasts, acting via hypoxia-induced factor regulations and epigenetic changes., A. Dvořák, J. Zelenka, K. Smolková, L. Vítek, P. Ježek., and Obsahuje bibliografii
At present, there are insufficient information about baroreflex sensitivity (BRS) and factors that determine BRS in premature newborns. The objective of this study was to determine the relationship between BRS and the characteristics that reflecting the intrauterine development (gestational age and birth weight), as well as postnatal development (postconception age and the actual weight of the child at the time of measurement). We examined 57 premature infants, who were divided into groups according to gestational age and postconception age as well as birth weight, and weight at the time of measurement. Continuous and noninvasive registration of peripheral blood pressure (BP) was perf ormed in every child within 2-5 m in under standard conditions using a Portapres (FMS) device. The results showed a close correlation of baroreflex sensitivity, heart rate and respiratory rate with gestational age, postconception age, birth weight and actual weight at the time of measureme nt premature newborns. An increase in the characteristics (ages and weights) resulted in increased BRS and diastolic arterial pressure (DAP), and in decreased heart and respiratory rates. Baroreflex sensitivity in the first week was in the group of very premature newborns the lowest (4.11 ms/mmHg) and in the light premature newborns was almost double (8.12 ms/mmHg). BRS increases gradually in relation to postnatal (chronological) and to postconception age as well as to birth and actual weight. The multifact or analysis of BRS identified birth weight and postconception age as the best BRS predictors. The two independent variables together explained 40 % of interindividual BRS variability., K. Haskova, M. Javorka, B. Czippelova, M. Zibolen, K. Javorka., and Obsahuje bibliografii