Genetic aspects of exercise and rhabdomyolysis.

Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle constituents into the circulation. Consequently, the circulatory levels of intracellular molecular components, such as creatine kinase, are commonly used to evaluate the severity of muscle damage. Nevertheless, there is a wide inter-individual variability in the phenotypic expression of muscle damage, which cannot be predicted by the age, race, body composition, and fitness level of each subject. This suggests that apart from environmental factors, genetic factors might also contribute to the development and progression of exercise-induced muscle damage. Recently, several gene-specific single nucleotide polymorphisms (SNPs) were found to be associated with severe exercise-induced muscle damage. The present manuscript reviews the pathophysiology of exertional muscle damage, emphasizing the influence of gene polymorphisms on its inter-individual severity. This knowledge may be useful for pediatricians for identifying individuals more susceptible to severe exertional muscle damage and related life-threatening comorbidities.

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.

Effects of percutaneous transluminal coronary angioplasty on cardiopulmonary responses during exercise.

AIM: The aim of this study was to examine by means of percutaneous transluminal coronary angioplasty (PTCA) whether dilating blocked coronary arteries in patients with coronary heart disease will improve relevant attributes measured during cardiopulmonary exercise testing (CPET). METHODS: Fourteen myocardial ischemia patients (13 male, 1 female; age range: 42-72 years), who were referred for cardiac catheterization, participated in the study. Eight patients underwent PTCA (experimental group) and 6 did not (control group). All subjects performed CPET about 2 weeks before and 3 weeks after cardiac catheterization. RESULTS: The results of electrocardiogram (ECG) analysis reveal a very low predictive accuracy (36%) for identifying coronary heart disease and/or anatomical changes caused by the PTCA. However, selected CPET parameters in the experimental group only showed significant post-PTCA changes from baseline. Peak oxygen uptake (VO(2)) increased from 17.49 to 20.75 mL x kg(1) x min(1), ventilatory anaerobic threshold from 12.15 to 14.39 mL x kg(1) x min(1), peak oxygen pulse (O(2)pulse) from 11.76 to 13.27 mL x beat(1), and O(2)pulse slope from 7.05 to 9.25, slope category. No significant inter- or intra-group differences were found in peak exercise heart rate, respiratory exchange ratio, subjective rating of perceived exertion, or systolic and diastolic blood pressure. CONCLUSIONS: This study suggests that selected CPET parameters seem to be highly sensitive to changes in cardiac function caused by the PTCA, significantly more than with conventional stress ECG. These findings merit further investigation.

Combinations of etchants, composite resins, and bracket systems: an important choice in orthodontic bonding procedures.

The objectives of this investigation were: (1) to compare the shear bond strengths (SBS) of metal, ceramic, and plastic brackets using different concentrations of maleic and phosphoric acid gels and aqueous solutions, and (2) to determine if a relationship exists between the type of acid etchant and the location of resin after debonding. A sample of 210 bovine incisors was divided among three different bracket groups (Victory series metal, Transcend 6000 ceramic, Spirit MB plastic). Prior to bonding, enamel was acid-etched using 37% phosphoric acid (H3PO4) gel and aqueous solution, 10% maleic acid gel and aqueous solution, 10% H3PO4 gel and aqueous solution, or 2% H3PO4 aqueous solution. SBS testing and the adhesive remnant index (ARI) score provided insight into the effects of the bonding process on enamel. Resin tags associated with each etchant type were inspected under scanning electron microscopy (SEM). Statistical analyses (level of significance, p = 0.05) of the data showed significant differences among groups. It was concluded that specific acid-composite-bracket combinations are recommended for use in clinical orthodontic practice in order to achieve efficient bonding.

The relationship between bond strength and orthodontic bracket base surface area with conventional and microetched foil-mesh bases.

The aim of this study was to test the effects on the shear bond strength by sandblasting bracket base surfaces, reducing base surface area, and etching enamel with various acid types. Four different base sizes, used as either standard (untreated), sandblasted or microetched were bonded with Phase II resin (Reliance Orthodontic Products, Inc.) in four groups of 12 bovine enamel specimens after enamel etching with phosphoric acid gel (37%), 37% phosphoric acid aqueous solution, 10% maleic acid gel, or 10% maleic acid aqueous solution. Storage of samples was for 7 days in distilled water at room temperature before shear bond testing with an Instron universal testing machine with a crosshead speed of 0.5 mm/min. Statistical analyses included the analysis of variance, the Student t test, and the Chi-square test at p < 0.05. An increase in shear bond strength was associated with sandblasting and microetching of foil-mesh bases for all base sizes (p < 0.05). No statistically significant difference in shear bond strength existed between the three larger base sizes, which indicated that shear bond strength is independent of surface area between 6.82 and 12.35 mm2. A reduction in bond strength was associated with the reduction of base surface area from 6.82 to 2.38 mm2 (p < 0.05). There appears to be no need to increase base surface area beyond 6.82 mm2. Aqueous maleic acid (10%) etching of the enamel was associated with the highest shear bond strength, with no statistically significant difference between the other three acids used.

Tyrosine 3-hydroxylase in rat brain and adrenal medulla: hybridization histochemistry and immunohistochemistry combined with retrograde tracing.

Rat brain and adrenal gland were analyzed by hybridization histochemistry using an RNA probe complementary to mRNA for tyrosine 3-hydroxylase (TyrOHase; tyrosine 3-monooxygenase, EC 1.14.16.2), by immunohistochemistry using TyrOHase antiserum, and by retrograde tracing using the fluorescent compound Fast blue. Cell bodies in the ventral mesencephalon contained mRNA for TyrOHase, and these cells were also TyrOHase immunoreactive. After injection of Fast blue into the striatum, such double-labeled cells in addition contained the retrograde tracer, showing that these cells send axonal projections to the injection site. These results show that hybridization histochemistry can be used to identify transmitter-specific neuron populations and that their projections can be established.