27Moderate physical exercise does not cause any changes in the plasma levels of the catabolic hormone cortisol and the anabolic hormone testosterone compared with the concentrations during a control day. In studies on army recruits, however, fit compared to unfit men tended to have smaller mean decreases in plasma testosterone and free testosterone index during the day both during a control day and during a day with submaximal marching exercise. After 4 months training, the mean plasma testosterone and free testosterone index tended to decrease less during both control and marching exercise days, and this was more evident in the well-conditioned subjects. However, very fit male athletes, who have been training for many years, and sedentary men have identical plasma testosterone levels and serum sex hormone binding globulin binding capacities (SHBG). Intense physical exercise invariably leads to an increase in plasma cortisol and a decrease in plasma testosterone compared with the concentrations during a control day. However, the percentage of free testosterone seems to increase cornpensatorily, which in many individuals keeps the absolute free testosterone level constant or even higher despite no change or slight increase in SHBG. Prolonged exhaustive physical exercise in men results in a decrease in plasma testosterone even down to normal female levels, and there is a constant increase in SHBG resulting in very low free testosterone concentrations. It is known from studies in rats that a low level of androgens results in an increase in the binding of cortisol in muscle tissue probably due to an increase in the number of cortisol receptors. This in combination with the high level of cortisol during prolonged exhaustive physical exercise may lead to a situation in which the protein catabolic events in the muscle cells supersedes the anabolic ones. Rats trained on a treadmill and sedentary rats have identical plasma and testicular testosterone concentrations, identical plasma LH levels, and training has no effect on Leydig cell LH and prolactin receptors. When these rats ran until exhaustion, the trained rats were able to run much longer (up to 3 h) than the untrained rats. In this experiment, the decrease in plasma testosterone was greater in the trained rats compared with the untrained ones, and also the testicular concentration of testosterone, androstenedione, and progesterone fell to lower levels in the trained rats after the exhaustive exercise. The plasma LH levels remained unchanged. This suggests that the decrease in plasma testosterone is due to a reduction in testicular testosterone production and a depletion of the testosterone stores and that the testosterone-LH feedback mechanism is no longer functioning in these exhausted animals. However, when the Leydig cells were incubated in vitro with HCG at different concentrations, it could be shown that in trained rats Leydig cell testosterone and cyclic AMP production was significantly greater than in sedentary rats. All these results are in good agreement w...

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ∼2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2×10−8) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0×10−9). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1×10−7), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

The global epidemic of chronic non-communicable diseases is closely related to changes in lifestyle, including decreasing leisure time physical activity (PA). Physical inactivity is a major public health challenge. To respond to that challenge, it is essential to know which personal and environmental factors affect PA behaviour. Certain life events may be one contributing factor, by creating emotional distress and disrupting a person's daily routine. The aim was to examine the literature concerning the effects of life events on changes in PA. A systematic literature search was performed on studies that assessed at least one major change in life circumstances and a change in PA. To be included, studies had to assess PA at two timepoints at least (before and after the event). Diseases as life events were excluded from this review. Thirty-four articles met the inclusion criteria. The studies examined the following life-change events: transition to university; change in employment status; marital transitions and changes in relationships; pregnancy/having a child; experiencing harassment at work, violence or disaster; and moving into an institution. The studies reviewed showed statistically significant changes in leisure PA associated with certain life events. In men and women, transition to university, having a child, remarriage and mass urban disaster decreased PA levels, while retirement increased PA. In young women, beginning work, changing work conditions, changing from being single to cohabiting, getting married, pregnancy, divorce/separation and reduced income decreased PA. In contrast, starting a new personal relationship, returning to study and harassment at work increased PA. In middle-aged women, changing work conditions, reduced income, personal achievement and death of a spouse/partner increased PA, while experiencing violence and a family member being arrested or jailed decreased PA. In older women, moving into an institution and interpersonal loss decreased PA, while longer-term widowhood increased PA. In addition, experiencing multiple simultaneous life events decreased PA in men and women. Major life events have a strong effect on leisure PA behaviour. Consequently, people experiencing life events could be an important target group for PA promotion. More research is needed to examine the short- and long-term effects of different life events on PA, gender differences in the effects of life events and the specific determinants of PA change during life events.

To investigate respiratory symptoms, increased bronchial responsiveness, and signs of airway inflammation in elite swimmers, we examined 29 swimmers from the Finnish national team and 19 healthy control subjects (nonasthmatic, symptom‐free). They answered a questionnaire and were interviewed for respiratory symptoms. Lung volumes were measured and bronchial responsiveness assessed by a histamine challenge test. Induced sputum samples were also collected. Fourteen (48%) of the swimmers and three (16%) of the control subjects showed increased bronchial responsiveness (P<0.05). The sputum cell differential counts of eosinophils (mean 2.7% vs 0.2%) and neutrophils (54.7% V5 29.9%) from swimmers were significantly higher than those from controls (P<0.01). Eosinophilia (sputum differential eosinophil count of >4%) was observed in six (21%) of the swimmers and in none of the controls (P<0.05). Symptomatic swimmers had significantly more sputum eosinophils than did the symptom‐free. The concentrations of sputum eosinophil peroxidase (EPO) and human neutrophil lipocalin (HNL) were significantly higher in swimmers than control subjects (P<0.001 and P=0.05). We conclude that elite swimmers had significantly more often increased tjronchial responsiveness than control subjects. Sputum from swimmers contained a higher percentage of eosinophils and neutrophils, and higher concentrations of EPO and HNL than sputum from controls. Long‐term and repeated exposure to chlorine compounds in swimming pools during training and competition may contribute to the increased occurrence of bronchial hyperresponsiveness and airway inflammation in swimmers.

The benefits of living and training at altitude (HiHi) for an improved altitude performance of athletes are clear, but controlled studies for an improved sea-level performance are controversial. The reasons for not having a positive effect of HiHi include: (1) the acclimatization effect may have been insufficient for elite athletes to stimulate an increase in red cell mass/haemoglobin mass because of too low an altitude (< 2000-2200 m) and/or too short an altitude training period (<3-4 weeks); (2) the training effect at altitude may have been compromised due to insufficient training stimuli for enhancing the function of the neuromuscular and cardiovascular systems; and (3) enhanced stress with possible overtraining symptoms and an increased frequency of infections. Moreover, the effects of hypoxia in the brain may influence both training intensity and physiological responses during training at altitude. Thus, interrupting hypoxic exposure by training in normoxia may be a key factor in avoiding or minimizing the noxious effects that are known to occur in chronic hypoxia. When comparing HiHi and HiLo (living high and training low), it is obvious that both can induce a positive acclimatization effect and increase the oxygen transport capacity of blood, at least in 'responders', if certain prerequisites are met. The minimum dose to attain a haematological acclimatization effect is > 12 h a day for at least 3 weeks at an altitude or simulated altitude of 2100-2500 m. Exposure to hypoxia appears to have some positive transfer effects on subsequent training in normoxia during and after HiLo. The increased oxygen transport capacity of blood allows training at higher intensity during and after HiLo in subsequent normoxia, thereby increasing the potential to improve some neuromuscular and cardiovascular determinants of endurance performance. The effects of hypoxic training and intermittent short-term severe hypoxia at rest are not yet clear and they require further study.