A novel dietary restriction method for group-housed rats: weight gain and clinical chemistry characterization.

Laboratory rodents are usually fed ad libitum. Moderate dietary restriction decreases mortality and morbidity compared with ad libitum feeding. There are, however, problems in achieving dietary restriction. Traditional methods of restricted feeding may interfere with the diurnal rhythms of the animals and are not compatible with group-housing of rodents. We have invented a novel method, the diet board, for restricting the feed intake of laboratory rats. The use of the diet board moderately decreased weight gain of rats when compared with ad libitum-fed animals. The diet board retarded skeletal growth only minimally, whereas major differences were found in body fat depositions. Serum free fatty acid, triglyceride and cholesterol values were lower in diet-restricted rats, while the opposite was true for serum creatine kinase. There were no differences in total protein, albumin or alanine aminotransferase. Moreover, differences in interindividual variances in parameters were not detected between the groups; hence this study could not combine the diet board with reduction potential. The diet board provides mild to moderate dietary restriction for group-housed rats and is unlikely to interfere with the diurnal eating rhythm. The diet board can also be seen as a cage furniture item, dividing the open cage space and increasing the structural complexity of the environment. In conclusion, the diet board appears to possess refinement potential when compared with traditional methods of dietary restriction.

The association of bone metabolism with bone mineral density, serum sex hormone concentrations, and regular exercise in middle-aged men.

Physical activity is an important factor in attaining bone mass. Our aim was to investigate if low to moderate intensity exercise affects bone resorption [serum tartrate-resistant acid phosphatase (TRAP) 5b activity] and formation (serum osteocalcin concentration) in a randomized controlled exercise intervention trial in Finnish middle-aged men. In addition, the relations of these bone turnover markers with bone mineral density (BMD) and serum sex hormone concentrations [circulating testosterone (T), estradiol (E2), and sex hormone-binding globulin (SHBG) concentrations] were evaluated. Serum TRAP 5b activity and osteocalcin concentration were measured at randomization and after 1 and 4 years of the exercise intervention. BMDs of the lumbar spine (L2-L4), femoral neck, and total proximal femur were measured with a dual-energy X-ray absorptiometry (DXA). At randomization, TRAP 5b activity was strongly correlated with the osteocalcin concentration (Spearman r = 0.541, P < 0.0001). In addition, TRAP 5b activity was significantly correlated with proximal femur BMD values (r = -0.201, P = 0.018) and osteocalcin concentration with femoral neck and proximal femur BMD values (r = -0.187, P = 0.028; r = -0.240, P = 0.005, respectively). Serum E2, free E2, and free T concentrations were inversely correlated with both bone turnover markers. After 1 year of exercise intervention, TRAP 5b activity was significantly lower in the exercise than reference group (P = 0.006). However, after 4 years of exercise intervention, the difference was no longer statistically significant. There were no differences in the osteocalcin concentrations between the study groups during the intervention. Our results show a connection between serum TRAP 5b activity and osteocalcin concentration. Furthermore, our results suggest that low to moderate exercise intervention and serum sex hormone concentrations may induce changes in bone metabolism in middle-aged men. However, exercise-induced effects on bone metabolism should be confirmed in other randomized controlled exercise trials taking into account exercise intensity and dose-response issues.

Cardiorespiratory fitness modifies the association between dietary fat intake and plasma fatty acids.

OBJECTIVES: To investigate the relation between (1) cardiorespiratory fitness and plasma saturated, monounsaturated and polyunsaturated fatty acids and (2) the interactions between cardiorespiratory fitness, dietary fat intake and plasma fatty acid composition. DESIGN: Cross-sectional analysis. SETTING AND SUBJECTS: The subjects were randomly selected, 127 middle-aged Finnish men participating in the DNASCO exercise intervention study. INTERVENTIONS: Cardiorespiratory fitness was determined spiroergometrically, dietary intake of macro- and micronutrients by 4-day food records and plasma fatty acids by gas chromatography. The subjects were divided into tertiles of aerobic fitness. RESULTS: Differences between fitness tertiles were not observed for dietary intake of total fat, and saturated, monounsaturated or polyunsaturated fatty acids (percent of total energy). In contrast, plasma saturated fatty acids were significantly lower (P <0.01) and polyunsaturated fatty acids significantly higher (P <0.05) in the highest fitness tertile compared to the lowest tertile. Dietary saturated fat intake was positively associated with plasma saturated fatty acids (r=0.342; P <0.05) and inversely with plasma polyunsaturated fatty acids (r=-0.453; P <0.01) only in the lowest fitness tertile. In addition, a positive correlation between body mass index and plasma saturated fatty acids (r=0.516; P <0.01) as well as a negative correlation between body mass index and plasma polyunsaturated fatty acids (r=-0.516; P <0.01) was observed in the lowest tertile solely. CONCLUSION: Different levels in cardiorespiratory fitness are associated with different levels in plasma saturated and polyunsaturated fatty acids and lead to modifications in the association between dietary and plasma fatty acids. These findings can perhaps be explained by a reduced hepatic fatty acid and lipoprotein synthesis as well as by an enhanced muscular lipid utilization, which are commonly seen in those who are physically active and who exhibit a higher level of fitness.

Aerobic exercise and bone mineral density in middle-aged finnish men: a controlled randomized trial with reference to androgen receptor, aromatase, and estrogen receptor alpha gene polymorphisms.

Our aim was to investigate associations of the polymorphic loci of androgen receptor (AR), aromatase CYP19, and estrogen receptor alpha (ERalpha) genes with bone mineral density (BMD) in a four-year controlled randomized exercise intervention trial in Finnish middle-aged men. Additionally, we studied whether the gene polymorphisms affect circulating testosterone (T), estradiol (E(2)), and sex hormone-binding globulin concentrations. The polymorphic CAG repeat of the AR gene, the TTTA repeat of the human aromatase gene, and the PvuII site of the ERalpha gene were analyzed. BMDs of the lumbar spine (L2-L4), femoral neck, and total proximal femur were measured with a dual-energy X-ray absorptiometry (DXA). In the exercise group, the subjects with the ERalpha gene PP or Pp genotypes showed an increase (+6.5 and +5.1%, respectively) in lumbar spine BMDs (P = 0.007; repeated measures ANOVA) during intervention, while there was no change in the subjects with the pp genotype. The long TTTA repeat (TTTA(9-12)) in aromatase gene was associated with greater height (P = 0.026) and lower BMI (P = 0.029) values than the short TTTA repeat (TTTA(6-8)). With regard to the AR gene, no statistically significant differences in bone properties were found between the genotypes. There were no significant associations of any analyzed polymorphic sites with the serum sex steroid hormone concentrations in the exercise or reference group. In conclusion, the Finnish middle-aged men with ERalpha PP or Pp genotypes appear to have increased BMD values in the lumbar spine. This increase may reflect a predisposition to age-related degenerative changes in the spine. In addition, the AR CAG repeat and aromatase TTTA repeat do not modify the effect of regular aerobic exercise on BMD.

Relation of sex hormones to bone mineral density in middle-aged men during a 4 year exercise intervention trial.

Recent studies have emphasized the symbiotic role of estradiol and testosterone on bone metabolism. Several anthropomorphic-, lifestyle-, and dual-energy X-ray (DXA)-derived parameters were measured with respect to estradiol (E(2)), testosterone (T), free T (fT), and sex hormone-binding globulin (SHBG) in 140 men (aged 53-62 years) participating in a controlled, randomized exercise intervention trial. After 4 years of intervention, 132 (94.3%) men remained as participants. During the period of study, aerobic threshold increased significantly in the exercise intervention group compared with the reference group (13.4% vs. -1.9%: p < 0.023). Serum E(2) and fT were not convincingly related to bone mineral density (BMD) or BMD change. Aerobic threshold or the change in aerobic threshold were not associated with sex hormone or SHBG levels. Body mass index was a significant determinant of T (beta = -0.337), fT (beta = -0.293), and SHBG (beta = -0.306), and smoking predicted T (beta = 0.231) and fT (beta = 0.245). Alcohol intake was a significant determinant of E(2) (beta = 0.213). Ultimately there was no convincing relation between sex hormone levels and BMD or BMD change in middle-aged men.

Coeliac disease in children and adolescents with type 1 diabetes: a study of growth, glycaemic control, and experiences of families.

UNLABELLED: The aim of this study was to evaluate whether coeliac disease affects growth, glycaemic control, and general well-being of children and adolescents with type I diabetes. Eighteen subjects were found to have coeliac disease by a screening program. Gastrointestinal symptoms, changes in growth and the levels of glycated haemoglobin (GHbA1) were analysed, as well as subjective well-being before and after diagnosis of coeliac disease. Overt gastrointestinal symptoms and deterioration of growth prior to disclosure of coeliac disease were seen only in one patient who had both of these conditions. Retrospectively, most subjects reported mild gastrointestinal complaints, which resolved on a gluten-free diet. Introduction of a gluten-free diet did not have any positive effect on glycaemic control, but was associated with an increase in weight-for-height (from 4.3+/-18.1 to 8.2+/-15.4% deviation from population median, p = 0.02). This increase in weight-for-height was inversely correlated with changes in GHbA1 (r = -0.574, p = 0.02). CONCLUSION: Coeliac disease is rarely associated with signs of malabsorption in children and adolescents with type I diabetes. Introduction of a gluten-free diet may be associated with excess weight gain. We recommend intensified follow-up for these subjects.

Regular physical exercise and bone mineral density: a four-year controlled randomized trial in middle-aged men. The DNASCO study.

The aim of the study was to investigate the effects of regular aerobic exercise training on bone mineral density (BMD) in middle-aged men. A population based sample of 140 men (53-62 years) was randomly assigned into the exercise and reference groups. BMD and apparent volumetric BMD (BMDvol) of the proximal femur and lumbar spine (dual-energy X-ray absorptiometry, DXA) and anthropomorphic measurements were performed at the randomization and 2 and up to 4 years later. The participation rate was 97% and 94% at the second and third BMD measurements, respectively. As another indication of excellent adherence and compliance, the cardiorespiratory fitness (aerobic threshold) increased by 13% in the exercise group. The 2% decrease in the reference group is regarded as an age-related change in cardiorespiratory fitness. Regardless of the group, there was no association between the increase in aerobic threshold and change in BMD. In the entire group, age-related bone loss was seen in the femoral neck BMD and BMDvol (p < 0.01). BMD and BMDvol values increased with age in L2-L4 (p < 0.004). An increased rate of bone loss at the femoral neck was observed in men with a low energy-adjusted calcium intake (p = 0.003). Men who increased their alcohol intake during the intervention showed a decrease in the rate of bone loss at the femoral neck (p = 0.040). A decrease in body height associated with decreased total femoral BMD (r = 0.19, p = 0.04) and the change in body height was a predictor of bone loss in the femoral neck (beta = 0.201). Long-term regular aerobic physical activity in middle-aged men had no effect on the age-related loss of femoral BMD. On the other hand, possible structural alterations, which are also essential for the mechanical strength of bone, can not be detected by the DXA measurements used in this study. The increase seen in lumbar BMD reflects age-related changes in the spine, thus making it an unreliable site for BMD follow-up in men.

Dose-response and coagulation and hemostatic factors.

PURPOSE: The purpose of this study was to evaluate the dose-response relations of regular physical activity on platelet function, blood coagulation factors, and fibrinolytic factors, on the basis of studies with appropriate experimental design. METHODS: MEDLINE-based literature search supplemented with relevant review articles and other individual articles was used. The review concentrates on controlled randomized clinical trials on the impact of regular physical exercise on platelet function, and on blood coagulation and fibrinolytic factors. RESULTS: Physical exercise acutely activates platelets and the fibrinolytic system, and some factors of the blood coagulation cascade. These findings, the earliest of which were published already in the 1960s, are mainly derived from uncontrolled observations. These studies have led to the conclusion that unbalanced activation of the hemostatic system during acute exercise may be part of the mechanisms for sudden cardiac events during or shortly after heavy physical exercise. The effects of regular physical exercise on various aspects of platelet function, blood coagulation, and fibrinolysis have been the object in only a few controlled randomized trials. With the exception of data on platelet function, the results remain contradictory. CONCLUSION: Controlled randomized clinical trials with adequate statistical power and experimental study designs with subjects of different ages and health status are warranted for the evaluation of the dose-response issues to clearly delineate the preventive and therapeutic potential of regular physical exercise.

Vitamin D(3) analogs (MC 1288, KH 1060, EB 1089, GS 1558, and CB 1093): studies on their mechanism of action.

Selected 20-epi and 20-normal vitamin D(3) analogs were studied. First, point mutations were introduced into human vitamin D receptor (VDR) to identify residues important for ligand binding. In helices three, four and five, His229, Asp232, Ser237 and Arg274 seem to have an important role in the binding of calcitriol. Surprisingly, the 20-epi analog MC 1288 did not bind to Ser237. Second, the effects of analogs on VDR degradation were studied. The transcriptionally active 20-epi analogs protected VDR against degradation more efficiently than the 20-normal analogs and calcitriol. With proteasome inhibitor MG-132 formation of Sug-1-RXRbeta-VDR-VDRE complex was detected. The 20-epi analogs effectively prevented its formation. Thus, the 20-epi analogs induce a VDR conformation, which prevents binding of factors mediating VDR degradation. Third, the analogs were found to be powerful regulators of cell cycle progression in MG-63 cells. They arrested cell cycle in the G0/G1 phase at lower concentrations and earlier time points than calcitriol. This was accompanied by hypophosphorylation of Rb followed by strong inhibition of Cdk2 activity. This correlated with increased levels of p27. Cdk2 and cyclin E levels were downregulated but those of p21 and cyclin D1 were not affected. Thus, a similar sequence of events with calcitriol and the analogs in inhibiting MG-63 cell growth was detected but the analogs had much longer lasting and stronger effects than calcitriol. A unifying scheme for the varying effects of vitamin D(3) analogs is presented.

Stromelysin-1 and interleukin-6 gene promoter polymorphisms are determinants of asymptomatic carotid artery atherosclerosis.

The functional 5A/6A polymorphism of the stromelysin-1 promoter has been implicated as a potential genetic marker for the progression of angiographically determined atherosclerosis in patients with coronary artery disease. Recently, a novel interleukin-6 (IL-6) gene functional G/C polymorphism at -174 in the promoter has also been reported. In this study, we analyzed the relation of these two polymorphisms with carotid artery atherosclerosis in 109 randomly selected, middle-aged men without exercise-induced ischemia. Atherosclerosis was quantified as intima-media thickness (IMT) by high-resolution ultrasonography. Univariately, stromelysin genotype was significantly (P:=0.015) associated with IMT, and this relation remained (P:=0.033) after adjustments for age, cardiorespiratory fitness, body mass index, smoking, LDL cholesterol, and systolic blood pressure and for sonographers. The 5A/6A polymorphism independently explained 7% of the variance in carotid bifurcation IMT. The IL-6 polymorphism was also significantly associated (P:=0. 036) with increased IMT, with men homozygous for the G allele having IMT that was 11% greater than men homozygous for the C allele. Men who were homozygous for both the 6A and G alleles had an covariate adjusted IMT that was 36% greater than men who were homozygous for neither allele (P:<0.003). These data suggest that genetic factors that predispose to reduced matrix remodeling (stromelysin 6A allele) and to increased inflammation (IL-6 G allele) combine to increase susceptibility for intima-media thickening in the carotid bifurcation, a predilection site for atherosclerosis.

Determinants of bone mineral density in middle aged men: a population-based study.

Osteoporosis is a growing health problem not only in women but also in men. To assess determinants of bone mineral density (BMD) at the spine and proximal femur, a randomly selected sample of 140 Finnish men aged 54-63 years was measured using fan beam dual-energy X-ray absorptiometry. Isometric muscle strength was measured using a computerized measurement system and cardiorespiratory fitness was assessed with maximal oxygen uptake (VO2 max) using breath-by-breath respiratory gas analyses during an incremental bicycle ergometer exercise. Intakes of calcium and energy were estimated using 4-day food records. Smoking habits and alcohol consumption were assessed from an interview and a 4 week diary, respectively. Isometric muscle strength of triceps and biceps brachii, extensors and flexors of thigh and rectus abdominis correlated significantly with BMD (r = 0.18-0.35, p = 0.02-0.000). Calcium intake correlated positively with femoral (r = 0.19-0.28, p = 0.03-0.003), but not with lumbar BMD. In addition, calcium intake adjusted for dietary energy content (mg/MJ) correlated with femoral BMD (r = 0.25-0.36, p = 0.03-0.000). Smoking had no effect on BMD, whereas alcohol intake correlated positively with BMD at L2-L4 (r=0.19, p = 0.031). In the multiple linear regression analysis adjusted calcium intake predicted BMD in every site measured, while strength of abdominal muscles predicted BMD at Ward's triangle and femoral neck. Body weight was a predictor of trochanteric BMD. Body height was the best predictor of lumbar and femoral neck area. We conclude that low dietary calcium intake, weak muscle strength and low body weight are risk factors for low BMD in men.

Relationship between lipid peroxidation and plasma fibrinogen in middle-aged men.

The relationship between lipid peroxidation (plasma malondialdehyde [MDA] concentration) and plasma fibrinogen level was analyzed in 144 men, aged 53-62 years. MDA was measured colorimetrically and fibrinogen with the thrombin method. Mean plasma MDA concentration was 12.6 (SD 1.2) micromol/L, plasma fibrinogen level 2.91 (0.47) g/L, and body mass index 27.1 (3.5) kg/m(2). Prevalence of smoking was 17%. MDA correlated moderately with fibrinogen. Both MDA and fibrinogen correlated positively with waist hip ratio (WHR) and blood leukocyte count, but inversely with VO(2)max. Both MDA and fibrinogen levels were higher in smokers than in non-smokers (p<0. 01). In multiple stepwise regression analysis, plasma MDA, VO(2)max, smoking, and leukocyte count explained 38.1% of the variance in plasma fibrinogen level, with the individual contributions reaching 20.6%, 9.7%, 5.5%, and 2.3%, respectively. WHR, serum triglycerides, and age did not enter the model. These data suggest that increased lipid peroxidation is associated with elevated plasma fibrinogen level in middle-aged men.

The RsaI polymorphism in the alpha-fibrinogen gene and response of plasma fibrinogen to physical training--a controlled randomised clinical trial in men.

We have previously reported cross-sectional data on an interaction effect between physical activity and alpha-fibrinogen RsaI polymorphism on fibrinogen in postmenopausal women. In the present controlled randomised study, we investigated the role of the RsaI polymorphism in determining the response of fibrinogen to long-term regular exercise. Middle-aged men (n = 140), randomly selected from the population registry, were randomised into an exercise or a reference group for a 3-year low intensity exercise intervention. Complete data were available in 125 men. The RsaI restriction enzyme detects threonine (Thr) to alanine change in the fibrinogen alpha codon 312. Anaerobic ventilatory threshold increased by 4%, but decreased by 2% in the exercise and reference groups, respectively. Mean fibrinogen did not decrease in either study group. However, in the exercise group, individual changes in anaerobic threshold explained 48% of the variance in fibrinogen changes in the Thr homozygotes. Our data offer a new aspect of beneficial effects of regular physical exercise on risk factors for coronary heart disease.

Physical activity in the prevention and treatment of a thrombogenic profile in the obese: current evidence and research issues.

PURPOSE: To evaluate the impact of regular physical activity on thrombogenic profile in obese individuals. DESIGN: Medline-based literature search with emphasis on controlled randomized clinical trials. The focus was on the impact of physical activity on platelet aggregation, fibrinogen, and plasminogen activator inhibitor-1(PAI-1) in overweight and obese subjects. RESULTS: Physical activity increases acutely 1) platelet number and activity, 2) activation of coagulation leading to a thrombin generation, and 3) simultaneous activation of fibrinolysis. On the other hand, hemostatic changes resulting from regular exercise training are limited to few data on platelets and blood coagulation and to some indications of increased fibrinolysis. Obesity is a risk factor for atherosclerotic cardiovascular diseases, and it is associated with hypertriglyceridemia, hyperinsulinemia, and non-insulin-dependent diabetes (NIDDM). These states interfere with a balance between blood coagulation and fibrinolysis leading to an increased thrombogenesis. Regular physical activity reduces platelet aggregability, while the effects on plasma fibrinogen and fibrinolytic activity remain unclear. CONCLUSIONS: Although obesity associates with several unfavorable derangements in the hemostatic system, data on the interactions of regular physical activity with blood coagulation in overweight or obese subjects are scarce. Therefore, controlled randomized clinical trials with adequate statistical power are needed for the evaluation of physical activity in the prevention and treatment of obesity-related atherothrombotic disorders.

Interaction of physical activity and diet: implications for haemostatic factors.

Regular moderate intensity physical activity and habitual diet providing no more than one third of energy from fats have been recommended for the prevention of atherosclerotic diseases. The background for these guidelines is the key role of plasma lipids. However, the importance of thrombogenesis in acute myocardial infarction has become obvious during the last decade. Hyperlipidaemia and excess of adipose tissue increase platelet aggregability and blood coagulation, and decrease fibrinolysis. Both regular physical activity and dietary fat reduction decrease blood lipids and body fat thereby diminishing the risk of thrombosis. Currently, data on interactions between physical activity and diet on haemostasis are scarce, and the few studies available have not demonstrated additional effects when these two lifestyle modifications have been combined. This paper is restricted only to studies using controlled randomized design. Regular moderate intensity physical activity as well as diet rich in omega-3 fatty acids decrease platelet aggregability. The effects of regular physical activity on plasma fibrinogen remain contradictory, while the impact of diet is even less clear. Plasminogen activator inhibitor-1, a possible link between insulin resistance syndrome and coronary heart disease, may decrease due to physical training or low fat diet. It can be hypothesized that moderation in physical activity and diet carries a more powerful impact on blood coagulation and fibrinolysis than either lifestyle modification alone. Studies focusing on the interactions of regular moderate physical activity and fat-modified diet are needed in efforts to optimize the preventive actions by lifestyle changes.

Adherence to the salt restriction diet among people with mildly elevated blood pressure.

OBJECTIVE: The aim of the study was to examine the adherence to a salt restriction diet and the effect of salt restriction on blood pressure in free living subjects with mildly elevated blood pressure. DESIGN: Subjects with mildly elevated blood pressure participated in a controlled study on the effect of salt restriction on blood pressure. Subjects received oral and written instructions by a clinical nutritionist to reduce sodium chloride intake to five grams per day. A low sodium bread (0.5%) was supplied free of charge for the subjects during the whole low-sodium period (between weeks 4-24). SUBJECTS AND METHODS: Subjects were recruited from previous studies at the Kuopio Research Institute of Exercise Medicine and from local occupational health care services. Twenty-four men and 15 women aged 28-65 y with the mean daytime ambulatory diastolic blood pressure between 90-105 mmHg and office diastolic blood pressure between 95-115 mmHg were included in the study. Salt intake was monitored by 4-d food diaries and 24-h urinary sodium excretion. RESULTS: Twenty percent of the subjects achieved a urinary sodium excretion level of less than 74 mmol/24 h corresponding to a salt intake of five grams per day. There was a significant decline (7.1+/-12.7/4.2+/-7.5) in systolic and diastolic blood pressure levels during the salt restriction diet. CONCLUSIONS: Even moderate salt restriction seems to be effective in the treatment of mildly elevated blood pressure. However, the recommended salt intake level of less than five grams per day is difficult to achieve even after intensive counselling and regular use of low salt bread.

The importance of the putative helices 4 and 5 of human vitamin D(3) receptor for conformation and ligand binding.

The 3-D structure of the human vitamin D(3) receptor has not been solved to date. To study the conformation of the ligand binding pocket and the amino acid residues important for binding of calcitriol and its synthetic 20-epi analog MC1288, we have introduced several point mutations into putative helices 4 and 5 of human vitamin D(3) receptor by site-directed mutagenesis. The amino acid residues Ser256, Glu257, Asp258, Gln259, Lys264, Ser265, Ser266, Glu269, Arg274, Ser278, and Phe279 were substituted by alanine. Our results suggest that Arg274 is important for the binding of calcitriol and probably also for the binding of the synthetic vitamin D analog MC1288, whereas Asp258, Gln259, Glu269, and Phe279 may have an important role in stabilizing the conformation of hVDR after ligand binding.

Regular exercise, plasminogen activator inhibitor-1 (PAI-1) activity and the 4G/5G promoter polymorphism in the PAI-1 gene.

The aim of this controlled randomised clinical trial was to investigate the effects of regular low to moderate intensity physical activity on plasminogen activator inhibitor-1 (PAI-1) activity during three years while taking into account the 4G/5G polymorphism in the promoter of the PAI-1 gene. Male subjects (age 52-62 years, n = 132) were randomised into an exercise or a (non-intervention) reference group. Aerobic threshold increased by 8.8% (p = 0.025) in the exercise group, and decreased by 1.1% in the non-intervention group, while PAI-1 activity did not change significantly in either study group. However, homozygotes for the 4G allele in the exercise group showed a 36% reduction in PAI-1 (p = 0.025). In conclusion, although regular moderate physical activity did not decrease PAI-I activity in the whole group, regular exercise may be effective for controlling elevated PAI-1 level in subjects homozygous for the 4G allele.

Positive and negative life changes and LDL cholesterol.

Epidemiological studies have revealed that stressful changes in social environment increase the risk of cardiovascular mortality. In this study, the influence of major negative and positive life changes on serum cholesterol was examined in middle-aged men to determine a possible biochemical link between life changes and cardiovascular mortality. The results showed no influence of negative life changes on serum cholesterols. However, positive life changes significantly predicted a reduction in total and LDL (low-density lipoprotein) cholesterol levels after adjustment for the baseline cardiovascular health status, baseline cholesterol level, diet, body mass index, waist-to-hip ratio and cardiorespiratory fitness. The odds ratio for lowering LDL cholesterol was 5.2 in the men reporting positive events compared with those reporting none. The findings suggest a predictive value of positive life changes for atherogenic lipid profile in middle-aged men.