Influence of training status and exercise modality on pulmonary O2 uptake kinetics in pre-pubertal girls

The limited available evidence suggests that endurance training does not influence the pulmonary oxygen uptake (V(O)(2)) kinetics of pre-pubertal children. We hypothesised that, in young trained swimmers, training status-related adaptations in the V(O)(2) and heart rate (HR) kinetics would be more evident during upper body (arm cranking) than during leg cycling exercise. Eight swim-trained (T; 11.4 +/- 0.7 years) and eight untrained (UT; 11.5 +/- 0.6 years) girls completed repeated bouts of constant work rate cycling and upper body exercise at 40% of the difference between the gas exchange threshold and peak V(O)(2). The phase II V(O)(2) time constant was significantly shorter in the trained girls during upper body exercise (T: 25 +/- 3 vs. UT: 37 +/- 6 s; P < 0.01), but no training status effect was evident in the cycle response (T: 25 +/- 5 vs. UT: 25 +/- 7 s). The V(O)(2) slow component amplitude was not affected by training status or exercise modality. The time constant of the HR response was significantly faster in trained girls during both cycle (T: 31 +/- 11 vs. UT: 47 +/- 9 s; P < 0.01) and upper body (T: 33 +/- 8 vs. UT: 43 +/- 4 s; P < 0.01) exercise. The time constants of the phase II V(O)(2)and HR response were not correlated regardless of training status or exercise modality. This study demonstrates for the first time that swim-training status influences upper body V(O)(2) kinetics in pre-pubertal children, but that cycle ergometry responses are insensitive to such differences

Genetic Variants of the Renin Angiotensin System: Effects on Atherosclerosis in Experimental Models and Humans

The renin angiotensin system (RAS) has profound effects on atherosclerosis development in animal models, which is partially complimented by evidence in the human disease. Although angiotensin II was considered to be the principal effector of the RAS, a broader array of bioactive angiotensin peptides have been identified that have increased the scope of enzymes and receptors in the RAS. Genetic interruption of the synthesis of these peptides has not been extensively performed in experimental or human studies. A few studies demonstrate that interruption of a component of the angiotensin peptide synthesis pathway reduces experimental lesion formation. The evidence in human studies has not been consistent. Conversely, genetic manipulation of the RAS receptors has demonstrated that AT1a receptors are profoundly involved in experimental atherosclerosis. Few studies have reported links of genetic variants of angiotensin II receptors to human atherosclerotic diseases. Further genetic studies are needed to define the role of RAS in atherosclerosis

Pulmonary oxygen uptake and muscle deoxygenation kinetics during recovery in trained and untrained male adolescents

Previous studies have demonstrated faster pulmonary oxygen uptake ( V ˙ O 2 ) kinetics in the trained state during the transition to and from moderate-intensity exercise in adults. Whilst a similar effect of training status has previously been observed during the on-transition in adolescents, whether this is also observed during recovery from exercise is presently unknown. The aim of the present study was therefore to examine V ˙ O 2 kinetics in trained and untrained male adolescents during recovery from moderate-intensity exercise. 15 trained (15 ± 0.8 years, V ˙ O 2max 54.9 ± 6.4 mL kg−1 min−1) and 8 untrained (15 ± 0.5 years, V ˙ O 2max 44.0 ± 4.6 mL kg−1 min−1) male adolescents performed two 6-min exercise off-transitions to 10 W from a preceding “baseline” of exercise at a workload equivalent to 80% lactate threshold; V ˙ O 2 (breath-by-breath) and muscle deoxyhaemoglobin (near-infrared spectroscopy) were measured continuously. The time constant of the fundamental phase of V ˙ O 2 off-kinetics was not different between trained and untrained (trained 27.8 ± 5.9 s vs. untrained 28.9 ± 7.6 s, P = 0.71). However, the time constant (trained 17.0 ± 7.5 s vs. untrained 32 ± 11 s, P < 0.01) and mean response time (trained 24.2 ± 9.2 s vs. untrained 34 ± 13 s, P = 0.05) of muscle deoxyhaemoglobin off-kinetics was faster in the trained subjects compared to the untrained subjects. V ˙ O 2 kinetics was unaffected by training status; the faster muscle deoxyhaemoglobin kinetics in the trained subjects thus indicates slower blood flow kinetics during recovery from exercise compared to the untrained subjects

O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction

Background: The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP. Methods A computer-aided search of MEDLINE (1950-October 2009), EBSCO (1966-October 2009) and EMBASE (1974-October 2009) was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance. Results Of 254 studies identified as eligible for full-text review, 52 (20.5%) met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others) was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value. Conclusions Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease

Comparação entre diferentes métodos de análise do componente lento do consumo de oxigênio: uma abordagem no domínio muito intenso de exercício Comparison between different methods of analysis of slow component of oxygen uptake: a view in severe exercise domain

O objetivo do presente estudo foi comparar, em domínio muito intenso de exercício, diferentes técnicas utilizadas para medir a amplitude do componente lento (CL) da cinética do consumo de oxigênio. Dez ciclistas treinados, do gênero masculino [média &plusmn; DP (idade: 25 &plusmn; 3,6 anos, massa corporal: 67,2 &plusmn; 4,5kg, altura: 174,8 &plusmn; 6,5cm e VO2max: 62,4 &plusmn; 3,1ml.kg¹.min¹)], realizaram duas idênticas transições de carga constante (intensidade de 75%delta: 75% da diferença entre o VO2 no limiar de lactato e o VO2max) em dias diferentes. O CL foi calculado a partir de diferentes métodos: (1) modelo biexponencial [VO2(t) = VO2base + A1 (1 e-(t-TA1/t1)) + A2 (1 e(tTA2/t2))], (2) intervalos predeterminados (o deltaVO26-2: diferença do VO2 entre o segundo e o sexto minuto de exercício e o deltaVO263: diferença do VO2 entre o terceiro e o sexto minuto de exercício) e (3) diferença entre o VO2 obtido no final do exercício e o valor obtido a partir de um ajuste monoexponencial do "componente primário" (tempo predeterminado de 120s) (CL6"CP"). Todos os métodos foram comparados entre si. Os resultados demonstraram significante subestimação do CL obtido pelo método de intervalos predeterminados (deltaVO26-2: 432 &plusmn; 126ml.min¹ e deltaVO263: 279 &plusmn; 88ml.min¹) quando comparado com o modelo biexponencial (676 &plusmn; 136ml.min¹) e ao CL6"CP" [(719 &plusmn; 265ml.min¹ (p < 0,05)]. Não houve diferenças significativas entre as outras comparações. Os resultados sugerem que a utilização de tempos predeterminados pode subestimar o CL quando comparado com o modelo biexponencial e com o CL6"CP".<br>The objective of the present study was to compare in severe exercise domain, different techniques used for measuring the amplitude of the slow component (SC) of oxygen uptake kinetics. Ten trained cyclists, male (age: 25 &plusmn; 3.6 years, body mass: 67.2 &plusmn; 4.5 kg, height: 174.8 &plusmn; 6.5 cm and VO2max: 62.4 &plusmn; 3.1 mL.kg¹.min¹), performed two identical bouts transitions at constant load [mean &plusmn; SD (intensity 75%delta: 75% of the difference between the VO2 lactate threshold and the VO2max)] in different days. The SC was calculated from different methods: (1) bi-exponential model [VO2(t) = VO2base + A1 (1 e(tTA1/t1)) + A2 (1 e(tTA2/t2))], (2) predetermined intervals (deltaVO262: difference between the second min VO2 and the end VO2; deltaVO263: difference between the third min VO2 and the end VO2) and (3) difference between the end VO2 and the value obtained from a mono-exponential adjustment of the "primary component" (predetermined time of 120 s) (SC6"PC"). All the methods were compared among themselves. The results showed a significant underestimation of the SC obtained by method of predetermined intervals (deltaVO262: 432 &plusmn; 126 ml.min¹ and deltaVO26-3: 279 &plusmn; 88 ml.min-1) when compared with bi-exponential model (676 &plusmn; 136 ml.min-1) and SC6-"PC" [(719 &plusmn; 265 ml.min-1 (p < 0.05)]. There was not significant difference among the other comparison. The results suggest that the use of predetermined time may underestimate the SC when compared with bi-exponential model and SC6"PC"