Lack of Association Between Variants within the AHSG , HCRT and NPY2R Genes and Anthropometrical Parameters in Czech Post-Monica Study.

The aim of this study was to examine single nucleotide polymorphisms (SNPs) of candidate genes α 2-Heremans-Schmid glycoprotein ( AHSG , rs4917), Hypocretin ( HCRT , rs760282) and Neuropetide Y2 receptor (NPY2R , rs 1047214), which are known to have a potential effect on body mass index (BMI) and other indicators of obesity. A population study was performed in 2007/2008 on 2559 adults (1191 males and 1368 females) from the Czech post-MONICA project. The SNPs were examined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. We did not find any significant association between the examined SNPs and BMI across the whole population. A significantly lower triglyceride level was found in the AHSG gene CC homozygotes compared to T allele carriers in the entire population ( p = 0.009). In conclusion, we are not able to confirm the hypothesis that polymorphisms within the AHSG , HCRT and NPY2R genes are major genetic determinants of BMI and plasma lipids in the Czech-Slavonic population.

Effect of different types of dietary fatty acids on subclinical inflammation in humans.

Replacing SAFAs (saturated fatty acids) for vegetable PUFAs (polyunsaturated fatty acids) has a well documented positive effect on the lipoprotein pattern while the direct effect of dietary fatty acids composition on systemic inflammation remains to be proven. In well controlled randomised cross-over study with 15 overweight/obese postmenopausal women, the effect of dietary switch on systemic inflammation was investigated. A two 3 weeks dietary period either with predominant animal fat (SAFA, 29 caloric % SAFA) or vegetable fat (PUFA 25 % caloric % PUFA) were interrupted by wash-out period. The expected increasing effect on SAFA diet to LDL-C (low density cholesterol) and opposite effect of PUFA diet was documented following changes in fatty acid spectrum in VLDL (very low density cholesterol) particles. The switch from SAFA diet to PUFA diet produced a significant change of CRP (C-reactive protein) concentration (p<0.01) whereas similar trend of IL-18 did not reach statistical significance. In this study, previous in vitro results of different SAFA and PUFA proinflammatory effects with well documented molecular mechanisms were first proven in a clinical study. It could be stated that the substantial change of dietary fatty acid composition might influence proinflammatory effect in addition to traditional cardiovascular risk factors.

INSIG2 G-102A promoter variant exhibits context-dependent effect on HDL-cholesterol levels but not on BMI in Caucasians.

The INSIG2 (INSIG2 is primarily involved in the regulation of fatty acid and cholesterol synthesis) gene is suggested to be obesity related. An INSIG2 promoter variant, G-102A, has been detected and was demonstrated to be of potential functional significance. In two cohorts of middle-aged men, the association between this variant and BMI was suggested. We sought to replicate the association between the INSIG2 G-102A variant and BMI in three large Slavonic Caucasian populations. Further, we analysed the possible effect of this variant on BMI changes in a short-time intervention study. One thousand ninety-nine males and 1368 females (population- based Czech MONICA three-year cohort), 908 females from the 3PMFs study, together with 94 overweight (BMI > 27 kg/m2) females who underwent nine weeks of dietary/exercise intervention were genotyped for the INSIG2 G-102A variant using PCR-RFLP analysis. We could not detect any association between the INSIG2 G-102A variant and BMI or WHR with or without adjusting for age and gender in any population. Neither the BMI change nor anthropometric and lipid parameter changes were affected by the INSIG2 G-102A gene variant in intervened overweight females. However, MONICA females (but not males) carrying the common GG genotype had higher plasma levels of HDL cholesterol (GG homozygotes 1.51 ± 0.36 mmol/l vs. A allele carriers 1.45 ± 0.33; P < 0.05) in both surveys. Our results indicated that the G-102A INSIG2 polymorphism has no consistent effect on BMI in general populations, but could influence HDL cholesterol in females.

Body mass index change in females after short-time life style intervention is not dependent on the FTO polymorphisms.

Variants within the FTO gene are important determinants of body mass index (BMI), but their role in determination of BMI changes after combined dietary/physical activity intervention is unclear. We have analyzed 107 unrelated overweight non-diabetic Czech females (BMI over 27.5 kg/m(2), age 49.2+/-12.3 years). FTO variants rs17817449 (first intron) and rs17818902 (third intron) were genotyped. The life style modification program (10 weeks) consisted of an age-matched reduction of energy intake and exercise program (aerobic exercise 4 times a week, 60 min each). The mean BMI before intervention was 32.8+/-4.2 kg/m(2) and the mean achieved weight loss was 4.8+/-3.5 kg (5.3+/-3.5 %, max. -15.5 kg, min. +2.0 kg, p<0.01). No significant association between BMI decrease and FTO variants was found. Also waist-to-hip ratio, body composition (body fat, water, active tissue), lipid parameters (total, LDL and HDL cholesterol, triglycerides) glucose and hsCRP changes were independent on FTO variants. FTO variants rs17817449 and rs17818902 are not associated with BMI changes after combined short time dietary/physical activity intervention in overweight females.

[The coincidence of alcoholic liver cirrhosis and chronic pancreatitis]. / Soubezný výskyt alkoholické jaterní cirhózy a chronické pankreatitidy.

UNLABELLED: INTRODUCTION, STUDY AIM: Health consequences of alcoholism vary and include a wide range of pathological conditions from mental disorders to disorders of various parenchymatous organs. There are many differences between alcohol abusers, from the way they abuse alcohol to the nature of bodily harm. The aim of this prospective study was to map and correlate organ involvement with the type of alcohol abuse and smoking and dietary habits. METHODS: A prospective study analyzing a questionnaire on alcoholism, smoking, diet and lifestyle habits completed by 146 patients with liver cirrhosis and chronic pancreatitis. RESULTS: Of the 80 liver cirrhosis patients with the mean age of47.5 year (23-60 years, SD 8.58), 64 were men and 16 (20%) were women. Of the 60 chronic pancreatitis patients with the mean age of 37.8 year (23-60 years, SD 9.66), 60 were men and 6 (9.1%) were women. The mean daily alcohol intake was 57.7 g in patients with cirrhosis and 63.7 g per day in patients with pancreatitis. The first contact with alcohol before 15th year of age was reported by 25.8% of patients with pancreatitis and 8.8% of patients with cirrhosis. Age under 30 years as the period with the largest intake of alcohol was reported by 43.6% of patients with pancreatitis and 20.3% of patients with cirrhosis. There was a statistically significant difference in the type of alcohol used; patients with pancreatitis predominantly drank beer. 16.7% of patients with pancreatitis and 3.7% of patients with cirrhosis started to smoke before 15th year of age. 66.7% of patients with pancreatitis and 40% of patients with cirrhosis left education before achieving collage state exam, 9.1% of patients with pancreatitis and 25% of patients with cirrhosis had university education. Cirrhosis was diagnosed in 11 (16.7%) patients with chronic pancreatitis. In all patients, this was functional disorder Child-Pugh stage A, decompensation occurred in 54.5% of patients. Portal hypertension was diagnosed in 72.7% of patients and thrombosis of v. portae orv. lieanlis in 12 patients. Bleeding from gastroesophageal varices occurred in 1 patient with chronic pancreatitis, liver cirrhosis and v. portae thrombosis. Chronic pancreatitis was diagnosed in 2 (2.5%) patients with livercirrhosis. With respect to comorbidities, chronic obstructive bronchopulmonary disease and ischemic heart disease was significantly more frequent in patients with chronic pancreatitis. CONCLUSION: There are differences in social-behavioural background of both relatively common organ disorders. Chronic pancreatitis is more prevalent in people with lower education. The first contact with alcohol and regular abuse occur at younger age, smoking is also more frequent, with earlier onset. Both diseases rarely occur concurrently and simultaneous decompensation of both organs is not seen. We could speculate that early exposition to the known aetiopathogenic factors affect primarily pancreas. The rare concurrence of both diseases, particularly of their advanced stages, opposes all known theories.

May alcohol-induced increase of HDL be considered as atheroprotective?

It is well known that the consumption of moderate doses of alcohol leads to the increase of HDL-cholesterol (HDL-C). Atheroprotectivity of HDL particles is based primarily on their role in reverse cholesterol transport (RCT). In the study with a cross-over design 13 male volunteers were studied in two different regimens: i) drinking of 36 g alcohol daily and ii) drinking only non-alcoholic beverages, to test whether alcohol-induced increase of HDL cholesterol can affect cholesterol efflux (CHE) from cell culture of labeled human macrophages. Alcohol consumption induced significant (p < 0.05) increases of HDL cholesterol from 1.25 +/- 0.32 to 1.34 +/- 0.38 mmol/l and Apo A1 from 1.34 +/- 0.16 to 1.44 +/- 0.19 g/l. These changes were combined with a slight increase of cholesterol efflux from 13.8 +/- 2.15 to 14.9 +/- 1.85 % (p = 0.059). There were significant correlations between individual changes of HDL-C and Apo A1 concentrations and individual changes of CHE (0.51 and 0.60, respectively). In conclusion, moderate alcohol consumption changes the capacity of plasma to induce CHE only at a border line significance.

Association between duration of the sleep and body weight.

Some studies have suggested that there could be an association between the duration of sleep in humans and development of the obesity. We have analyzed the group of the probands (n = 3970, 2038 males and 1932 females, aged 18-65 years), with permanent address in the Central or South Bohemia. We ascertained the relationship between the duration of their sleep (obtained per questionnaire) and body mass index, weight, height, the value of systolic and diastolic blood pressure, heart rate, waist and hip circumference, the values of total-, high density- and low density- cholesterol, thyroid hormone and body exercise performed. The optimal values of the body mass index (and optimal body weight) were associated with the duration of sleep 7 hours per night (P < 0.001). This association was found both in males and females and in both districts. Other anthropometrical and biochemical parameters were not associated with the sleep duration.

Life style change and reverse cholesterol transport in obese women.

HDL cholesterol resp. apolipoprotein A1 concentrations are tools to estimate individual CVD risk, although only a part of HDL particles participate in reverse cholesterol transport (RCT). This discrepancy was analyzed in life style change based on increase of physical activity and dietary counseling. Efflux of cholesterol from pre-labeled macrophages to plasma acceptors of tested individuals was used as an RCT measure. Changes of lipoprotein parameters, glucose, fasting insulin concentrations and RCT were analyzed in 15 obese women after 9-week intervention consisted of 5 sessions of increased physical activity per week. Controlled increase in physical activity for 9 weeks induced a decrease of body weight averaging 9 kg (ranged from 2.3 to 15.5 kg). The intervention leads to significant decreases of triglycerides, apoprotein A1 and apoprotein B concentration, whereas total cholesterol, LDL cholesterol and HDL cholesterol did not change significantly. The increase of RCT was not significant, but there was highly significant negative correlation between individual decrease of body weight and an increase of RCT. Significant increase of RCT was found in 13 persons with a weight reduction more than 3.5 kg. Substantial weight loss is necessary to increase RCT.

Actigenetic of ACE gene polymorphism in Czech obese sedentary females.

Obesity is a serious health problem worldwide and many genes have been implicated in determination of obesity, but our knowledge of the genes responsible for individual differences in weight loss after physical intervention are poor. One of the candidate genes is a gene for angiotensin-converting enzyme (ACE) ant its insertion/deletion (I/D) polymorphism. We have analyzed the association between the ACE gene variant in intervened obese females. Twenty four unrelated healthy obese (BMI > 29.9 kg/m(2), with abdominal type of obesity) premenopausal (age between 25 and 45 years) Czech Caucasian sedentary and non-diabetic females, pre-selected according the ACE I/D polymorphism (twelve II and twelve DD homozygotes) were studied in a medical research centre. They underwent 9 weeks intervention program (combination of the lowering of dietary intake to optimal level for the age and 3 times a week physical activity at fitness centre). The participants were supervised to sustain a heart rate of 65 % of maximum. Anthropometrical, biochemical parameters and body composition (Bodystat 1500) were analyzed before and after the intervention. Our study suggest, that in Czech Caucasian females I/D polymorphism within the ACE gene will have no major effect on weight loss. Interestingly, we have detected, that in obese females II genotype was associated with higher increase in basal metabolic rate (202 kcal per day) then in DD homozygotes (p<0.05), thus at least under some circumstances, this genetic variant may have an slight effect on BMI development.

Apolipoprotein A5 in health and disease.

High plasma levels of triglycerides (TG) are an independent risk factor in the development of cardiovascular disease, with about 50 % of the final levels being determined genetically. Apolipoprotein A5 (APOA5) is the last discovered member of the apolipoprotein APOA1/C3/A4 gene cluster, found by comparative sequencing analysis. The importance of APOA5 gene for determination of plasma triglyceride levels has been suggested after development of transgenic and knock-out mice (transgenic mice displayed significantly reduced TG, whereas knock-out mice had high TG). In Czech population, alleles C-1131 and Trp19 are associated with elevated levels of plasma TG and higher risk of myocardial infarction development. These alleles also play some role in nutrigenetics and actigenetics of lifestyle interventions leading to the plasma cholesterol changes as well as in the pharmacogenetics of statin treatment. On the contrary, APOA5 mutations detected in Czech population did not show strict effect on plasma TG levels. Val153 --> Met variant exhibit the sex-specific effect of HDL-cholesterol levels. The suggested roles of APOA5 variants in determination of the plasma remnant particles, plasma concentrations of C-reactive protein or some anthropometrical parameters were excluded.

Proinflammatory status, genetics and atherosclerosis.

Over the last decade, C-reactive protein concentration analyzed by the high sensitivity method (hsCRP) has been proven as a marker of premature atherosclerosis. Concentration exceeding 2 mg/l represents an increased individual risk of myocardial infarction and stroke but strict application of this borderline is complicated by relations of CRP concentrations to other risk factors of cardiovascular diseases. In a large 1 % representative sample of the Czech population, a positive relation of hsCRP to BMI, a waist circumference and triglyceride concentration was documented. Substantial sex differences were found in its relationship to age. Whereas it is continuously increasing in men, this increase appears in women only after menopause. A substantial decrease of body weight and visceral fat volume by increased physical activity is accompanied by significant decrease of hsCRP in young obese women. This decrease was not related to a change of interleukin-6 concentration, although it is supposed to regulate CRP production. CRP concentration is partly under genetic control as a higher concentration in young siblings of probands with proved coronary atherosclerosis was documented. The participation of genes related to lipoprotein metabolism (genes for apolipoprotein CI and apolipoprotein E) influence hsCRP concentrations. We hypothesized that an increased concentration of hsCRP represents a certain marker of proinflammatory status related to central obesity and triglyceride metabolism and it might be related to individual properties of monocytes in atherogenesis.

Changes of plasma lipids during weight reduction in females depends on APOA5 variants.

BACKGROUND: Apolipoprotein A5 (APOA5) is a determinant of plasma lipids, and its role in body mass index (BMI) determination is discussed. This study was aimed at the investigation of the relationship between common APOA5 gene variants and body weight/plasma lipid decrease in overweight females. METHODS: We analyzed 98 unrelated overweight and obese nondiabetic Czech females (BMI >27.5). APOA5 T-1131-->C and Ser19-->Trp variants were genotyped. Before and after 9 weeks of lifestyle modification, biochemical and anthropometrical measurements and assessment of nutritional intake were performed. The lifestyle modification program consisted of a reduction in energy intake and an exercise program (aerobic exercise 4 times per week, 60 min each). RESULTS: The mean age of the participants was 30.7 +/- 3.7 years, the mean BMI before the intervention was 31.4 +/- 3.8 and the weight loss was 5.9 +/- 2.5 kg (7 +/- 3%). There were 86 T-1131T homozygotes and 12 carriers of the C-1131 allele and 82 Ser19Ser homozygotes and 16 carriers of the Trp19 allele, respectively; 72 females had the commonest T-1131T/Ser19Ser haplotype. No significant association between BMI decrease and APOA5 variants was found, but T-1131T carriers have a significantly higher body weight both before and after the intervention (p < 0.05; p = not significant for BMI). The fasting glycemia was significantly higher in Trp19 carriers both before and after the intervention (p < 0.01). Further, plasma triglyceride levels decreased in Ser19Ser homozygotes but increased in Trp19 carriers (1.42 +/- 0.62 to 1.28 +/- 0.48 vs. 1.15 +/- 0.47 to 1.41 +/- 0.80 mmol/l; p < 0.05 for differences between the groups). Similarly, in carriers of at least 1 less common APOA5 allele (n = 26), plasma low-density lipoprotein cholesterol levels did not decrease as they did in T-1131T/Ser19Ser carriers (3.11 +/- 0.70 to 3.27 +/- 0.81 vs. 3.39 +/- 0.81 to 3.16 +/- 0.86 mmol/l; p < 0.05 for differences between the groups). CONCLUSIONS: APOA5 gene variants have effects on the decrease in plasma triglyceride and low-density lipoprotein cholesterol level in females in a model combining their dietary habits and physical activity changes.

Replacement of dietary saturated FAs by PUFAs in diet and reverse cholesterol transport.

Dietary intervention is the first and usually successful approach in the treatment of high LDL cholesterol (LDL-C) concentration, but it is frequently accompanied by a decrease in HDL concentration. We studied 14 male volunteers on two different diets, high saturated fatty acid (SFA) and high PUFA, in a crossover design to test whether a decrease in HDL can affect reverse cholesterol transport from relabeled macrophages. A significant decrease of LDL-C (in mmol/l) after a PUFA diet compared with an SFA diet from 3.15 +/- 0.65 to 2.80 +/- 0.56 (P < 0.01) was accompanied by a significant decrease of HDL cholesterol (HDL-C) (in mmol/l) from 1.21 +/- 0.30 to 1.10 +/- 0.32 (P < 0.05). These changes did not affect cholesterol efflux (CHE) from macrophages (9.74 +/- 1.46% vs. 9.53 +/- 1.41%). There was no correlation between individual changes of HDL-C and changes of CHE. It is concluded that the decrease of HDL-C after successful dietary intervention of LDL-C is not accompanied by a decrease of CHE.

The A-204C polymorphism in the cholesterol 7alpha-hydroxylase (CYP7A1) gene determines the cholesterolemia responsiveness to a high-fat diet.

The aim of the study was to ascertain whether the A-204C polymorphism in the cholesterol 7 -hydroxylase (CYP7A1) gene plays any role in determining LDL-cholesterol (LDL-C) concentration responsiveness to a high-fat diet. The concentrations of total cholesterol and LDL-cholesterol were measured in eleven healthy men (age: 30.9+/-3.2 years; BMI: 24.9+/-2.7 kg/m(2);;) who were homozygous for either the -204A or -204C allele, after 3 weeks on a low-fat (LF) diet and 3 weeks on a high-fat (HF) diet. During both dietary regimens, the isocaloric amount of food was provided to volunteers; LF diet contained 22 % of energy as a fat and 2.2 mg of cholesterol/kg of body weight a day, HF diet 40 % of fat and 9.7 mg of cholesterol/kg of body weight a day. In six subjects homozygous for the -204C allele, the concentrations of cholesterol and LDL-cholesterol were significantly higher on HF than on LF diet (cholesterol: 4.62 vs. 4.00 mmol/l, p<0.05; LDL-C: 2.15 vs. 1.63 mmol/l, p<0.01, respectively); no significant change was observed in five subjects homozygous for the -204A allele. There were no other differences in lipid and lipoprotein-lipid concentrations. Therefore, the polymorphism in the cholesterol 7alpha-hydroxylase promotor region seems to be involved in the determination of cholesterol and LDL-C responsiveness to a dietary fat challenge.

Quantification of intra-abdominal fat during controlled weight reduction: assessment using the water-suppressed breath-hold MRI technique.

A group of 14 healthy female subjects was studied using MRI during 2 months of life-style intervention. A series of 21 water-suppressed images was used to determine the intra-abdominal fat volume before and after the controlled loss of weight. The average weight decrease was 8.2 %, but the average relative loss of visceral fat was 20.3 %, whereas subcutaneous fat decreased by 13.4 %. A small but significant increase of insulin sensitivity (decrease in fasting insulin and blood glucose) was observed, but no changes in lipoprotein parameters were demonstrated. There was a significant negative correlation (r=-0.633, p=0.028) between the relative abdominal fat decrease and the initial amount of subcutaneous fat.

[Effect of acute urological complications on the course of pregnancy]. / Vplyv akútnych urologických príhod na priebeh gravidity.

OBJECTIVE: To evaluate influence of acute urological cases (AUC) on course and results of pregnancies. DESIGN: Retrospective clinical study. SETTING: 1st Department of Gynaecology and Obstetrics, Department Urology Faculty Hospital, Kosice, Slovakia. METHODS: 40 pregnant women with AUC aged 15-34 years (average 24) which delivered at our Department. RESULTS: The most often occurrence of AUC was in the 2nd and 3rd trimester of pregnancies. 62.5% women were primiparas. The most frequent urological complication was acute pyelonephritis (APNP)-23 (57%) patients, more often on the right side 4.75: 1. 27 patients (67.5%) had renal colic, more often presents on the right side (6:1). 83% women had infection of urinary tract (IUT). 34 (85%) women were treated by antibiotics or urodesinficiens. 70% pregnancies were closed as intact pregnancies without intrauterine risk of the fetus. Signs of premature labour had 8 patients (20%), hypotrophy of the fetus was evaluated in two patients (5%) and 2 pregnancies were terminated by caesarean section due to intrauterine asphyxia of the fetus. We identified nearly double increase of premature labours in the group of women with AUC in opposition to average in 1998 at Kosice district. Risk of newborn early asphyxia syndrome at the 1. minute is important (12.5%). CONCLUSION: Almost 1/3 pregnancies with AUC have obstetrical complication. Most common incidence of AUC is at the first gravidity, at the right side. AUC require complete obstetrical and urological examination with adequate therapy. We can reduce incidence by careful prenatal care and therapy.

A study of occupational exposure to isopropylbiphenyls (Sure Sol-250).

Environmental and medical examinations in workers exposed to the isopropylbiphenyl (IPBs) mixture, Sure Sol-250, in a capacitor-manufacturing plant were carried out once a year for three years. Levels of the total IPBs ranged from 0.03 to 36.6 mg/m3 with a mean of 5.6 mg/m3. The time-weighted average (TWA) exposures varied between 0.3 and 1.8 mg/m3. Physical and laboratory examinations (blood cell count, liver and kidney function tests and also antipyrine metabolism were normal) revealed no adverse effects of IPBs. Based on these observations as well as on the results of our six-month oral toxicity studies in rats, not presented in this paper, we recommend a TWA-MAC (maximum allowable concentration) of 10 mg/m3 for IPBs.

Analysis of polychlorinated biphenyls by high-performance liquid chromatography and capillary gas-liquid chromatography.

Seventy fractions were obtained by vacuum distillation of a PCB mixture containing 42% of chlorine. Four of these fractions were chosen, the composition of which covered the whole of the observed region, and analysed by means of high-performance liquid chromatography (HPLC) on silica gel using n-pentane as the mobile phase and capillary gas-liquid chromatography (GLC) using OV-101 and Carbowax 20M as stationary phases at 200 degrees C. The chosen distillation fractions were further prepared by HPLC, each yielding 10-14 samples. Individual PCB standards and all samples were analysed by HPLC and capillary GLC. These procedures permitted the identification of those compounds which are eluted simultaneously under the conditions used in either HPLC or capillary GLC alone.

Possibilities and limitations of capillary gas chromatography and mass spectrometry in the analysis of polychlorinated biphenyls.

The possibilities and limitations of analyses of polychlorinated biphenyls (PCBPs) by capillary gas chromatography and capillary gas chromatography-mass spectrometry have been investigated. Metal capillary columns (WCOT) coated with Apiezon L and OV-101 were not suitable for PCB analyses. Good results were obtained in the separation of model mixtures of PCBs and of Aroclor 1242 on a glass capillary column coated with OV-101. Sources of error are indicated that may be encountered in the characterization of PCB components in Aroclor 1242 by standard additions, Kováts' retention indices and mass spectrometry. The direct coupling of a capillary column (WCOT) to a mass spectrometer produced spectra of the main PCB components, many of which could be used in the identification of isomeric PCBs.