Osteocalcin and its forms respond similarly to exercise in males and females.

INTRODUCTION: Acute exercise increases osteocalcin (OC), a marker of bone turnover, and in particular the undercarboxylated form (ucOC). Males and females differ in baseline levels of total OC and it is thought the hormonal milieu may be driving these differences. Males and females adapt differently to the same exercise intervention, however it is unclear whether the exercise effects on OC are also sex-specific. We tested whether the responses of OC and its forms to acute High Intensity Interval Exercise (HIIE) and High Intensity Interval Training (HIIT) differed between males and females. Secondly, we examined whether sex hormones vary with OC forms within sexes to understand if these are driving factor in any potential sex differences. METHODS: Total OC (tOC), undercarboxylated OC (ucOC), and carboxylated OC (cOC) were measured in serum of 96 healthy participants from the Gene SMART cohort (74 males and 22 females) at rest, immediately after, and 3 h after a single bout of HIIE, and at rest, 48 h after completing a four week HIIT intervention. Baseline testosterone and estradiol were also measured for a subset of the cohort (Males = 38, Females = 20). Linear mixed models were used to a) uncover the sex-specific effects of acute exercise and short-term training on OC forms and b) to examine whether the sex hormones were associated with OC levels. RESULTS: At baseline, males had higher levels of tOC, cOC, and ucOC than females (q < 0.01). In both sexes tOC, and ucOC increased to the same extent after acute HIIE. At baseline, in males only, higher testosterone was associated with higher ucOC (ß = 3.37; q < 0.046). Finally, tOC and ucOC did not change following 4 weeks of HIIT. CONCLUSION/DISCUSSION: While there were no long-term changes in OC and its forms. tOC and ucOC were transiently enhanced after a bout of HIIE similarly in both sexes. This may be important in metabolic signalling in skeletal muscle and bone suggesting that regular exercise is needed to maintain these benefits. Overall, these data suggest that the sex differences in exercise adaptations do not extend to the bone turnover marker, OC.

DNA methylation across the genome in aged human skeletal muscle tissue and muscle-derived cells: the role of HOX genes and physical activity.

Skeletal muscle tissue demonstrates global hypermethylation with age. However, methylome changes across the time-course of differentiation in aged human muscle derived cells, and larger coverage arrays in aged muscle tissue have not been undertaken. Using 850K DNA methylation arrays we compared the methylomes of young (27 ± 4.4 years) and aged (83 ± 4 years) human skeletal muscle and that of young/aged heterogenous muscle-derived human primary cells (HDMCs) over several time points of differentiation (0, 72 h, 7, 10 days). Aged muscle tissue was hypermethylated compared with young tissue, enriched for; pathways-in-cancer (including; focal adhesion, MAPK signaling, PI3K-Akt-mTOR signaling, p53 signaling, Jak-STAT signaling, TGF-beta and notch signaling), rap1-signaling, axon-guidance and hippo-signalling. Aged cells also demonstrated a hypermethylated profile in pathways; axon-guidance, adherens-junction and calcium-signaling, particularly at later timepoints of myotube formation, corresponding with reduced morphological differentiation and reductions in MyoD/Myogenin gene expression compared with young cells. While young cells showed little alterations in DNA methylation during differentiation, aged cells demonstrated extensive and significantly altered DNA methylation, particularly at 7 days of differentiation and most notably in focal adhesion and PI3K-AKT signalling pathways. While the methylomes were vastly different between muscle tissue and HDMCs, we identified a small number of CpG sites showing a hypermethylated state with age, in both muscle tissue and cells on genes KIF15, DYRK2, FHL2, MRPS33, ABCA17P. Most notably, differential methylation analysis of chromosomal regions identified three locations containing enrichment of 6-8 CpGs in the HOX family of genes altered with age. With HOXD10, HOXD9, HOXD8, HOXA3, HOXC9, HOXB1, HOXB3, HOXC-AS2 and HOXC10 all hypermethylated in aged tissue. In aged cells the same HOX genes (and additionally HOXC-AS3) displayed the most variable methylation at 7 days of differentiation versus young cells, with HOXD8, HOXC9, HOXB1 and HOXC-AS3 hypermethylated and HOXC10 and HOXC-AS2 hypomethylated. We also determined that there was an inverse relationship between DNA methylation and gene expression for HOXB1, HOXA3 and HOXC-AS3. Finally, increased physical activity in young adults was associated with oppositely regulating HOXB1 and HOXA3 methylation compared with age. Overall, we demonstrate that a considerable number of HOX genes are differentially epigenetically regulated in aged human skeletal muscle and HDMCs and increased physical activity may help prevent age-related epigenetic changes in these HOX genes.

Investigating the influence of mtDNA and nuclear encoded mitochondrial variants on high intensity interval training outcomes.

Mitochondria supply intracellular energy requirements during exercise. Specific mitochondrial haplogroups and mitochondrial genetic variants have been associated with athletic performance, and exercise responses. However, these associations were discovered using underpowered, candidate gene approaches, and consequently have not been replicated. Here, we used whole-mitochondrial genome sequencing, in conjunction with high-throughput genotyping arrays, to discover novel genetic variants associated with exercise responses in the Gene SMART (Skeletal Muscle Adaptive Response to Training) cohort (n = 62 completed). We performed a Principal Component Analysis of cohort aerobic fitness measures to build composite traits and test for variants associated with exercise outcomes. None of the mitochondrial genetic variants but eight nuclear encoded variants in seven separate genes were found to be associated with exercise responses (FDR < 0.05) (rs11061368: DIABLO, rs113400963: FAM185A, rs6062129 and rs6121949: MTG2, rs7231304: AFG3L2, rs2041840: NDUFAF7, rs7085433: TIMM23, rs1063271: SPTLC2). Additionally, we outline potential mechanisms by which these variants may be contributing to exercise phenotypes. Our data suggest novel nuclear-encoded SNPs and mitochondrial pathways associated with exercise response phenotypes. Future studies should focus on validating these variants across different cohorts and ethnicities.

Genetic variants associated with exercise performance in both moderately trained and highly trained individuals.

Adaptation to exercise training is a complex trait that may be influenced by genetic variants. We identified 36 single nucleotide polymorphisms (SNPs) that had been previously associated with endurance or strength performance, exercise-related phenotypes or exercise intolerant disorders. A MassARRAY multiplex genotyping assay was designed to identify associations with these SNPs against collected endurance fitness phenotype parameters obtained from two exercise cohorts (Gene SMART study; n = 58 and Hawaiian Ironman Triathlon 2008; n = 115). These parameters included peak power output (PP), a time trial (TT), lactate threshold (LT), maximal oxygen uptake (VO2 max) in recreationally active individuals and a triathlon time-to-completion (Hawaiian Ironman Triathlon cohort only). A nominal significance threshold of α < 0.05 was used to identify 17 variants (11 in the Gene SMART population and six in the Hawaiian Ironman Triathlon cohort) which were significantly associated with performance gains in highly trained individuals. The variant rs1474347 located in Interleukin 6 (IL6) was the only variant with a false discovery rate < 0.05 and was found to be associated with gains in VO2 max (additional 4.016 mL/(kg min) for each G allele inherited) after training in the Gene SMART cohort. In summary, this study found further evidence to suggest that genetic variance can influence training response in a moderately trained cohort and provides an example of the potential application of genomic research in the assessment of exercise trait response.

A "human knockout" model to investigate the influence of the α-actinin-3 protein on exercise-induced mitochondrial adaptations.

Research in α-actinin-3 knockout mice suggests a novel role for α-actinin-3 as a mediator of cell signalling. We took advantage of naturally-occurring human "knockouts" (lacking α-actinin-3 protein) to investigate the consequences of α-actinin-3 deficiency on exercise-induced changes in mitochondrial-related genes and proteins, as well as endurance training adaptations. At baseline, we observed a compensatory increase of α-actinin-2 protein in ACTN3 XX (α-actinin-3 deficient; n = 18) vs ACTN3 RR (expressing α-actinin-3; n = 19) participants but no differences between genotypes for markers of aerobic fitness or mitochondrial content and function. There was a main effect of genotype, without an interaction, for RCAN1-4 protein content (a marker of calcineurin activity). However, there was no effect of genotype on exercise-induced expression of genes associated with mitochondrial biogenesis, nor post-training physiological changes. In contrast to results in mice, loss of α-actinin-3 is not associated with higher baseline endurance-related phenotypes, or greater adaptations to endurance exercise training in humans.

PGC-related gene variants and elite endurance athletic status in a Chinese cohort: a functional study.

This study aims to examine the association between proliferator-activated receptor γ (PGC)-gene family-related single nucleotide polymorphisms (SNPs) and elite endurance runners' status in a Chinese cohort, and to gain insights into the functionality of a subset of SNPs. Genotype distributions of 133 SNPs in PPARGC1A, PPARGC1B, PPRC1, TFAM, TFB1M, TFB2M, NRF1, GABPA, GABPB1, ERRα, and SIRT1 genes were compared between 235 elite Chinese (Han) endurance runners (127 women) and 504 healthy non-athletic controls (237 women). Luciferase gene reporter activity was determined in 20 SNPs. After adjusting for multiple comparisons (in which threshold P-value was set at 0.00041), no significant differences were found in allele/genotype frequencies between athletes and controls (when both sexes were analyzed either together or separately). The lowest P-value was found in PPARGC1A rs4697425 (P = 0.001 for the comparison of allele frequencies between elite female endurance runners and their gender-matched controls). However, no association (all P > 0.05) was observed for this SNP in a replication cohort from Poland (194 endurance athletes and 190 controls). Using functional genomics tool, the following SNPs were found to have functional significance: PPARGC1A rs6821591, rs12650562, rs12374310, rs4697425, rs13113110, and rs4452416; PPARGC1B rs251466 and rs17110586; and PPRC1 rs17114388 (all P < 0.001). This study found no significant association between PGC-related SNPs and elite endurance athlete status in the Chinese population, despite some SNPs showing potential functional significance and the strong biological rationale to hypothesize that this gene pathway is a candidate to influence endurance exercise capacity.

Exercise training and DNA methylation in humans.

The response to exercise training (trainability) has been shown to have a strong heritable component. There is growing evidence suggesting that traits such as trainability do not only depend on the genetic code, but also on epigenetic signals. Epigenetic signals play an important role in the modulation of gene expression, through mechanisms such as DNA methylation and histone modifications. There is an emerging evidence to show that physical activity influences DNA methylation in humans. The present review aims to summarize current knowledge on the link between DNA methylation and physical activity in humans. We have critically reviewed the literature and only papers focused on physical activity and its influence on DNA methylation status were included; a total of 25 papers were selected. We concluded that both acute and chronic exercises significantly impact DNA methylation, in a highly tissue- and gene-specific manner. This review also provides insights into the molecular mechanisms of exercise-induced DNA methylation changes, and recommendations for future research.

THE GSTP1 c.313A>G POLYMORPHISM MODULATES THE CARDIORESPIRATORY RESPONSE TO AEROBIC TRAINING.

The GSTP1 c.313A>G polymorphism is a candidate to explain some of the individual differences in cardiorespiratory fitness phenotypes' responses to aerobic exercise training. We aim to explore the association between the GSTP1 c.313A>G polymorphism and the response to low-high impact aerobic exercise training. Sixty-six Polish Caucasian women were genotyped for the GSTP1 c.313A>G polymorphism; 62 of them completed 12-week aerobic (50-75% HRmax) exercise training and were measured for selected somatic features (body mass and BMI) and cardiorespiratory fitness indices - maximal oxygen uptake (VO2max, maximum heart rate (HRmax), maximum ventilation (VEmax) and anaerobic threshold (AT) - before and after the training period. Two-factor analysis of variance revealed a main training effect for body mass reduction (p=0.007) and BMI reduction (p=0.013), improvements of absolute and relative VO2max (both p<0.001), and increased VEmax (p=0.005), but not for changes in fat-free mass (FFM) (p=0.162). However, a significant training x GSTP1 c.313A>G interaction was found only for FFM (p=0.042), absolute and relative VO2max (p=0.029 and p=0.026), and VEmax (p=0.005). As the result of training, significantly greater improvements in VO2max, VEmax and FFM were gained by the GG+GA group compared to the AA genotype group. The results support the hypothesis that heterogeneity in individual response to training stimuli is at least in part determined by genetics, and GSTP1 c.313A>G may be considered as one (of what appear to be many) target polymorphisms to influence these changes.

Genomic haplotype within the Peroxisome Proliferator-Activated Receptor Delta (PPARD) gene is associated with elite athletic status.

Peroxisome proliferator-activated receptor delta (PPARδ; encoded by the PPARD gene) plays a role in energy metabolism and mitochondrial function. We have investigated the distribution of PPARD rs2267668, rs2016520 and rs1053049 polymorphisms, individually and in haplotype, in a cohort of 660 elite athletes which was subdivided into four different groups based on the different metabolic demands of their respective sports and 704 healthy controls. PPARD rs2016529 and rs1053049 were individually associated with overall elite athletic performance (P = 0.00002; and P = 0.0002) and also with athletes grouped as strength endurance (P = 0.00008; and P = 0.0003). Furthermore, PPARD A/C/C haplotype (rs2267668/rs2016520/rs1053049) was significantly underrepresented in all athletes and each subgroup of athletes when compared with controls (P < 0.000001), suggesting that harboring this specific haplotype is unfavorable for becoming an elite athlete. These results help to identify which genetic profiles may contribute to elite athletic performance, specifically the role of variants within the PPARD gene, and may be useful in talent identification or optimizing the response to training.

GNAS A-1121G variant is associated with improved diastolic dysfunction in response to exercise training in heart failure patients.

ß1-adrenergic receptors (ADRB1) and Gαs proteins (GNAS) play important roles in the regulation of cardiac function. The present study sought to investigate whether ADRB1 Arg389Gly (rs1801253), GNAS -1211 G/A (rs6123837) and GNAS 2291 C/T (rs6026584) variants are associated with left ventricular function and exercise tolerance in heart failure patients. 61 heart failure patients completed a 6-month exercise-training programme. Left ventricular ejection fraction (LVEF), mitral inflow velocities (deceleration time, and E/A ratio) and exercise tolerance (METs) were assessed at baseline and following exercise training. There were no associations between the studied variants and LVEF or E/A ratio measured at baseline and after exercise training. Deceleration time of early mitral flow was higher at baseline in GNAS -1211G allele carriers compared with -1211A allele homozygotes (P<0.05). Exercise training attenuated deceleration time in -1211G allele carriers (P<0.05) but not in -1211A allele homozygotes. Moreover, ADRB1 389Gly homozygotes had a greater training-induced increase in exercise tolerance than 389Arg homozygotes (P=0.04). This study shows that the functional GNAS -1121 G/A polymorphism is associated with diastolic function at baseline and in response to exercise training in heart failure patients. Furthermore, our data suggest that ADRB1 Arg389Gly polymorphism may influence exercise tolerance.

The C allele in NOS3 -786 T/C polymorphism is associated with elite soccer player's status.

The NOS3-786 T/C polymorphism (rs2070744) is a candidate to explain individual variations in sports related phenotypes. We determined the genotype and allele frequency of NOS3-786 T/C in a group of 60 male professional elite soccer players. Their results were compared with those of 100 world-class endurance athletes, 53 elite power athletes, and 100 sedentary, healthy men (controls) of the same Caucasian (Spanish) origin. There were significant differences in genotype frequencies between soccer players, controls, endurance and power elite athletes (all P ≤ 0.02). These results were confirmed when we analysed allelic frequencies (all P<0.01). The likelihood of having the C allele was higher in soccer players compared with (i) controls [odds ratio (OR), 2.165, 95% confidence interval (CI): 1.362-3.441], (ii) endurance athletes (OR: 1.879, 95%CI: 1.184-2.984), and (iii) power athletes (OR: 4.032, 95%CI: 2.307-7.047). In conclusion, the -786C allele is associated with the status of being an elite soccer player, compared with non-athletic controls and also with elite endurance and power athletes. More research is needed in other groups of elite soccer players in order to replicate the results of the present study.

Is there an interaction between BDKRB2 -9/+9 and GNB3 C825T polymorphisms and elite athletic performance?

The -9 deletion allele in the BDKRB2 -9/+9 polymorphism was associated previously with improved endurance performance. We compared the frequency distribution of the BDKRB2 -9/+9 (rs5810761) polymorphism between athletes (n=155) of sports with different demands (endurance runners; n=74 vs sprinters; n=81) as well as between athletes of different competitive levels (elite level; n=46 vs national level; n=109). These results were compared with those of 240 non-athletic healthy individuals. We also tested the influence of the interaction between the BDKRB2 -9/+9 and the GNB3 C825T (rs5443) genotypes in relation to endurance performance. Genotype distribution and allele frequencies were found to be similar in the endurance athlete, sprinter, and control groups (P=0.83 for genotype distribution and P=0.9 for allele frequencies). Similarly, no statistical differences were found between the subgroups of elite-level endurance athletes and national-level endurance athletes, or between elite-level and national-level sprinters (P>0.09 for all comparisons). There was no interaction between BDKRB2 -9/+9 and GNB3 C825T polymorphisms in relation to endurance performance (P=0.16 for interaction effect). In conclusion, the BDKRB2 +9/-9 polymorphism is not associated with endurance performance, at least among Israeli athletes, and the GNB3TT+BDKRB2 -9/-9 "optimal genotype" is not associated with endurance performance.

GNB3 C825T Polymorphism and elite athletic status: A replication study with two ethnic groups.

We aimed to replicate the original findings by Eynon et al. showing an association between the T allele of the GNB3 C825T polymorphism and elite endurance athletic status, in larger cohorts and in other ethnicities. We compared allelic and genotypic frequencies of the GNB3 C825T polymorphism among non-athletic controls (N=340), elite endurance athletes (N=174), and power athletes (N=134). The population sample included participants from 2 different ethnic/geographic backgrounds (Israel and Spain). We observed no significant differences in genotypic and allelic frequencies between countries or groups (all P>0.1). The odds ratio (OR) of being an endurance athlete if the subject had a T allele was 0.841 (95%CI: 0.638-1.110) compared to the control group and 1.047 (95% CI: 0.751-1.461) compared to the power group. Our findings support the need to corroborate genotype:phenotype associations in the field of sports genetics with the largest possible population samples, including populations of different ethnic backgrounds.

Effect of different sprint training regimes on the oxygen delivery-extraction in elite sprinters.

AIM: The effects of sprint training regimes of varying distance schedules on the oxygen delivery-extraction relationship were investigated in 15 young (22+/-1 years) healthy males national-level sprinters. METHODS: During one session subjects performed four sprints, in a schedule of increasing distance order (100, 200, 300 and 400 m), and during the other session, in a schedule of decreasing distance order (400, 300, 200, and 100 m). All sprint bouts were performed on a treadmill at a speed of 22 km/h-1, which corresponds to 85% of subjects' maximal speeds. The order of the running sequences during sessions was balanced over subjects. RESULTS: During both sprint schedules, all variables except for oxygen extraction in the incremented training regime, increased significantly from rest to exercise. Training regimes were not different with regard to cardiac output and absolute oxygen uptake. However, the decreasing compared to the increasing scheme was characterized by significantly (P<0.05) higher mean values of heart rate (194.5+/-4.1 185.2+/-5.7 beats/min-1, respectively), oxygen extraction (54.3+/-3.8 and 47.1+/-3.4 mL/L-1, respectively) and lactate (10.6+/-0.5 and 9.2+/-0.7 mmol/L-1, respectively), while stroke volume was significantly (P<0.05) lower (100.4+/-4.5 and 109.7+/-4.4 mL, respectively). CONCLUSION: The present study indicates that in sprinters performing a similar distance at the same speed, but under different training regimes interplay exists between oxygen delivery and extraction, suggesting a link between the type of training scheme and physiological cardiovascular and skeletal muscle metabolic adaptations. This may explain the absence of differences between the conditions in absolute oxygen uptake and peak power output.

CK-MM gene polymorphism does not influence the blood CK activity levels after exhaustive eccentric exercise.

Gene variants, such as creatine kinase (CK) polymorphisms, have been suggested to explain the inter-individual blood CK response to eccentric exercise. However, since this association is still doubtful, the purpose of this study was to analyse the relationship between the magnitudes of the CK response to exercise with the occurrence of muscle CK-MM NcoI polymorphism in young healthy subjects. Blood CK activity was assessed in 70 subjects immediately before and 3, 24, 48, 72, 96, 120, 168 h after strenuous eccentric exercise. Based on the amount of CK release by each subject, the sample was distributed in quartiles and the genotype and allele frequency distribution was compared among quartiles. Despite the inter-individual variability of CK response observed between subjects, there were no differences in genotype and allele frequencies among quartiles. The results allowed us to conclude that CK response after exhaustive eccentric exercise is not associated with CK-MM Ncol polymorphism.

Do PPARGC1A and PPARalpha polymorphisms influence sprint or endurance phenotypes?

Functional Gly482Ser (rs8192678) and G/C (rs4253778) polymorphisms in the Peroxisome proliferator-activated receptor gamma coactivator1 (PPARGC1A) and Peroxisome proliferator-activated receptor alpha (PPARalpha) genes, respectively, have been associated with mRNA and protein activity. The aim of this study was to determine their frequency distribution among 155 Israeli athletes (endurance athletes and sprinters) and 240 healthy controls. Results showed that there was a significant difference in PPARGC1A Ser482Gly polymorphism genotype frequencies between endurance athletes and sprinters (P=0.005) as well as between endurance athletes and controls (P=0.0003). However, the sprinters' genotype and allele frequencies were similar to that of the control group. A significantly lower proportion of PPARGC1A Ser482 allele (0.25) was noted for the endurance athletes compared with controls (0.43, P=0.0001). Endurance athletes showed a trend of a higher yet a not significant proportion of the PPARalpha GG genotype compared with sprinters (P=0.051). As we compared between the subgroups of top-level endurance athletes and top-level sprinters, as well as between those of top-level and national-level endurance athletes, we reached more prominent results. In conclusion, our data indicate that a lower frequency of the Ser482 allele and possibly a higher frequency of the GG genotype are associated with increased endurance performance ability.

Is there an ACE ID - ACTN3 R577X polymorphisms interaction that influences sprint performance?

Functional R577X (rs.1815739) and ID (rs.5186) polymorphisms in the alpha-actinin-3 ( ACTN3) and the angiotensin converting enzyme (ACE) genes, respectively, have been associated with sprint performance. The aim of this study was to determine their effect on sprint performance among 81 Israeli sprinters and 240 healthy controls. Results revealed that the ACE II genotype+ ACTN3 R allele (P=0.003 for sprinters vs. controls), and the ACTN3 RR genotype +ACE I allele (P=0.001 for sprinters vs. controls) might be the genotype for sprinters. In the whole cohort the probability of ACTN3 RR genotype+ ACE I allele being a sprinter (odds ratio 2.67, 95% confidence interval 1.45-4.93) and of ACE II genotype+ ACTN3 R allele being a sprinter (odds ratio 3.57, 95% confidence interval 1.78-7.15) was significantly higher than that in the controls. In conclusion, the above data suggest that ACE ID/ ACTN3 R577X genotype combination is associated with sprint ability. However, ACE ID/ ACTN3 R577X genotype combination is not related to the level of performance.

ACTN3 R577X polymorphism and Israeli top-level athletes.

A common genetic variation in the alpha-actinin-3 ( ACTN3) gene causes a replacement of an arginine (R) with a premature stop codon (X) at amino-acid 577 (rs1815739). While the R allele has been found to be associated with power-oriented performance, the XX genotype may be linked with endurance ability. To test this hypothesis, we studied the distribution of ACTN3 genotypes in 155 Israeli athletes (age=35.9+12.2 years) classified by sport (endurance runners and sprinters) and in 240 sedentary individuals. The sprinters' allele frequencies (AF: R/X=0.7/0.3) and 577RR genotype distribution percentage (GD: RR=52%) differed markedly from those of the endurance athletes (AF: R/X=0.53/0.47, p=0.000007; GD: RR=18%, p=0.00009) and the control group (AF: R/X=0.55/0.45, p=0.0002; GD: RR=27.3%, p=0.000003). A comparison between the top-level and national-level sprinters revealed that the R allele occurs more often in the top-level sprinters. A significantly higher proportion of the XX genotype was observed in endurance athletes (34%) compared with controls (18%, p=0.02) and sprinters (13%, p=0.002). However, top-level and national level endurance athletes had similar allele and genotype frequencies. We conclude that the ACTN3 R allele is associated with top-level sprint performance and the X allele and XX genotypes may not be critical but rather additive to endurance performance.

Acute incremental exercise to maximal performance does not cause alterations in serum oxidant levels of healthy young individuals.

AIM: This study was designed to analyze serum oxidative stress (OS) levels in healthy young individuals performing a routine maximal aerobic exercise and to evaluate the correlation between OS levels and physiological parameters. METHODS: Serum OS levels were studied by thermochemiluminescence (TCL) parameters at rest and following maximal aerobic exercise in 85 healthy young subjects. Levels were measured by a real time on line TCL assay (higher TCL-Ratio and TCL-H3 = lower OS level). RESULTS: Aerobic capacity had no effect on baseline OS levels. Post-exercise OS levels correlated with maximal oxygen uptake (V.O(2max)) (P<0.005), delta V.O(2) (V.O(2max)- V.O(2)rest) (P<0.005), anaerobic threshold (VTH) (P<0.01), and total oxygen uptake (especially O(2) after VTH), (P<0.005). TCL-Ratio was related to total running time (P<0.01), as well. Post-exercise OS levels for the whole study group did not vary from baseline values. However, individuals with higher fitness level (V.O(2max) >percentile 60) had significantly lower values of TCL-H3 (P=0.04) and tended to have lower TCL-Ratio, indicating they had elevated OS levels. In a multivariate analysis OS level was most affected by V.O(2) after VTH (anaerobic phase of the test) (P=0.003; adjusted odds ratio of 3.41, 95% confidence interval: 1.55-7.48). CONCLUSIONS: In conclusion, acute incremental exercise to maximal performance does not cause alterations in serum oxidant levels of healthy young individuals. In healthy individuals performing maximal aerobic exercise, OS levels correlate with maximal aerobic power.

Lower respiratory tract infections in Inuit infants on Baffin Island.

BACKGROUND: It has long been suspected that Canadian Inuit children suffer from frequent severe lower respiratory tract infections (LRTIs), but the causes and risk factors have not been documented. This study assessed the infectious causes and other epidemiologic factors that may contribute to the severity of LRTI in young Inuit children on Baffin Island. METHODS: A prospective case study was carried out at the Baffin Regional Hospital in Iqaluit, Nunavut, of infants less than 6 months of age, who were admitted to hospital between October 1997 and June 1998 with a diagnosis of LRTI. Immunofluorescent antibody testing was used to identify respiratory viruses, and enzyme immunoassay (EIA) and polymerase chain reaction (PCR) were used to test for Chlamydia trachomatis. Demographic and risk factor data were obtained through a questionnaire. RESULTS: The annualized incidence rate of admission to hospital for bronchiolitis at Baffin Regional Hospital was 484 per 1000 infants who were less than 6 months of age; 12% of the infants were intubated. Probable pathogens were identified for 18 of the 27 cases considered in our study. A single agent was identified for 14 infants: 8 had respiratory syncytial virus, 2 adenovirus, 1 rhinovirus, 1 influenza A, 1 parainfluenza 3 and 1 had cytomegalovirus. For 4 infants, 2 infectious agents were identified: these were enterovirus and Bordetella pertussis, adenovirus and enterovirus, cytomegalovirus and respiratory syncytial virus, and respiratory syncytial virus and adenovirus. C. trachomatis was not identified by either EIA or PCR. All infants were exposed to maternal smoking in utero, second-hand smoke at home and generally lived in crowded conditions. INTERPRETATION: Inuit infants in the Baffin Region suffer from an extremely high rate of hospital admissions for LRTI. The high frequency and severity of these infections calls for serious public health attention.