A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0

Background: Glycogen storage disease type 0 is an autosomal recessive disease presenting in infancy or early childhood and characterized by ketotic hypoglycemia after prolonged fasting and postprandial hyperglycemia and hyperlactatemia. Sixteen different mutations have been identified to date in the gene which encodes hepatic glycogen synthase, resulting in reduction of glycogen storage in the liver. Case Presentation: Biochemical evaluation as well as direct sequencing of exons and exon-intron boundary regions of the GYS2 gene were performed in a patient presenting fasting hypoglycemia and postprandial hyperglycemia and her parents. The patient was found to be compound heterozygous for one previously reported nonsense mutation (c. 736 C>T; R243X) and a novel frameshift mutation (966_967delGA/insC) which introduces a stop codon 21 aminoacids downstream from the site of the mutation that presumably leads to loss of 51% of the COOH-terminal part of the protein. The glycemia and lactatemia of the parents after an oral glucose tolerance test were evaluated to investigate a possible impact of the carrier status on the metabolic profile. The mother, who presented a positive family history of type 2 diabetes, was classified as glucose intolerant and the father, who did not exhibit metabolic changes after the glucose overload, had an antecedent history of hypoglycemia after moderate alcohol ingestion. Conclusion: The current results expand the spectrum of known mutations in GYS2 and suggest that haploinsufficiency could explain metabolic abnormalities in heterozygous carriers in presence of predisposing conditions.

Métodos para identificar o limiar anaeróbio em indivíduos com diabete tipo 2 e em indivíduos não-diabéticos

FUNDAMENTO: Apesar de o limiar anaeróbio (LAn) ser utilizado na avaliação funcional de diferentes populações, estudos comparando métodos para sua identificação em diabéticos tipo-2 tem sido pouco realizados. OBJETIVO: Comparar protocolos de identificação do LAn em indivíduos diabéticos tipo 2 e em não-diabéticos, e analisar respostas relacionadas ao equilíbrio ácido-básico em intensidades relativas ao LAn. MÉTODOS: Diabéticos tipo 2 (n=10; 54,5±9,5 anos; 30,1±5,0 kg/m²) e jovens não-diabéticos (n=10; 36,6±12,8 anos; 23,9±5,0 kg/m²) realizaram teste incremental (TI) em ciclo ergômetro. O aumento desproporcional no equivalente ventilatório de oxigênio (VE/VO2) e lactatemia ([lac]) identificaram intensidades (Watts-W) correspondentes aos limiares ventilatório (LV) e de lactato (LL), respectivamente. A intensidade correspondente à menor glicemia ([glic]) foi considerada limiar glicêmico individual (LGI). O LAn também foi determinado por ajuste polinomial das razões VE/Watts (LV VE/W) e [lac]/Watts (LL[lac]/W), as quais identificaram intensidades acima das quais um aumento desproporcional na VE e [lac] ocorreram. RESULTADOS: Não foram observadas diferenças entre LL, LV, LG, LL[lac]/W e LV VE/W em diabéticos (85,0±32,1; 88,0±31,7; 86,0±33,8; 82,0±20,9 e 90,2±22,2W) e não-diabéticos (139,0±39,0; 133,0±42,7; 140,8±36,4; 122,7±44,3 e 133,0±39,1W). Contudo os valores de LAn diferiram significativamente entre grupos (p<0.001). A técnica de Bland-Altman confirmou concordância entre os protocolos. Reduções significativas no pH e pCO2 em paralelo a um aumento na [lac], pO2 e VE foram observadas em intensidades supra limiares. CONCLUSÃO: Os protocolos apresentaram, para ambos os grupos estudados, concordância na identificação do LAn, que se mostrou como uma intensidade de exercício acima da qual ocorre perda de equilíbrio ácido-básico.

Whole-Body Vibration Training Elevates Creatine-Kinase Levels in Sedentary Subjects

METHODS: 20 inactive (10 male, 10 female) underwent a single typical WBV session, with a total of 27 minutes of exercise on an oscillating platform at 26 Hz, involving upper and lower body muscles. Each exercise lasted 90 seconds, with 40 seconds pauses inbetween. Muscle enzymes (CK, transaminase, LDH, troponin I) were measured before, at 24, 48 and 96 hours post exercise. Lactate was measured immediately after the session. Muscle aches were assessed during 4 days post-exercise.RESULTS: Subjects' mean age was 23.0 ± 3.5 (male), 22.4 ± 1.4 (female), BMI 22.8 ± 2.3 and 22.1 ± 1.9, and all had been inactive for at least 12 months. Post exercise lactatemia was 10.0 ± 2.4 and 6.9 ± 2.4. CK elevation was significant (at least doubling of baseline values) in 1 male and 4 female subjects, while they remained at baseline values for the remaining 15 subjects. One female subject peaked at 3520 U/l at 96 hours post exercise, and all but one peaked at the same late time. Troponin and CK-MB never increased. No correlation was found between muscle soreness and CK levels.CONCLUSIONS: WBV can elicit important anaerobic processes reflected by the high lactacidemia, and CK elevation was significant in 25 % of subjects, peaking at the fourth day after exercise for 80 % of those. Such exercises should not be regarded as trivial and "easy" as they are advertised, since they can provoke important anaerobia and CK elevation. Many fragile patients or patients treated for cardiovascular disease could benefit from WBV but it is important to recognise these potential effects, especially in those treated with statins, known to cause a myopathy and CK elevation. Before considering a side effect of an important therapeutic agent, doctors should be aware of the possible interaction with not-so-harmless exercising machines.

Acute supra-therapeutic oral terbutaline administration has no ergogenic effect in non-asthmatic athletes.

This study aimed to investigate the effects on a possible improvement in aerobic and anaerobic performance of oral terbutaline (TER) at a supra-therapeutic dose in 7 healthy competitive male athletes. On day 1, ventilatory threshold, maximum oxygen uptake [Formula: see text] and corresponding power output were measured and used to determine the exercise load on days 2 and 3. On days 2 and 3, 8 mg of TER or placebo were orally administered in a double-blind process to athletes who rested for 3 h, and then performed a battery of tests including a force-velocity exercise test, running sprint and a maximal endurance cycling test at Δ50 % (50 % between VT and [Formula: see text]). Lactatemia, anaerobic parameters and endurance performance ([Formula: see text] and time until exhaustion) were raised during the corresponding tests. We found that TER administration did not improve any of the parameters of aerobic performance (p > 0.05). In addition, no change in [Formula: see text] kinetic parameters was found with TER compared to placebo (p > 0.05). Moreover, no enhancement of the force-velocity relationship was observed during sprint exercises after TER intake (p > 0.05) and, on the contrary, maximal strength decreased significantly after TER intake (p < 0.05) but maximal power remained unchanged (p > 0.05). In conclusion, oral acute administration of TER at a supra-therapeutic dose seems to be without any relevant ergogenic effect on anaerobic and aerobic performances in healthy athletes. However, all participants experienced adverse side effects such as tremors.

Effects of endotoxin on lactate metabolism in humans.

ABSTRACT: INTRODUCTION: Hyperlactatemia represents one prominent component of the metabolic response to sepsis. In critically ill patients, hyperlactatemia is related to the severity of the underlying condition. Both an increased production and a decreased utilization and clearance might be involved in this process, but their relative contribution remains unknown. The present study aimed at assessing systemic and muscle lactate production and systemic lactate clearance in healthy human volunteers, using intravenous endotoxin (LPS) challenge. METHODS: Fourteen healthy male volunteers were enrolled in 2 consecutive studies (n = 6 in trial 1 and n = 8 in trial 2). Each subject took part in one of two investigation days (LPS-day with endotoxin injection and placebo-day with saline injection) separated by one week at least and in a random order. In trial 1, their muscle lactate metabolism was monitored using microdialysis. In trial 2, their systemic lactate metabolism was monitored by means of a constant infusion of exogenous lactate. Energy metabolism was monitored by indirect calorimetry and glucose kinetics was measured with 6,6-H2 glucose. RESULTS: In both trials, LPS increased energy expenditure (p = 0.011), lipid oxidation (p<0.0001), and plasma lactate concentration (p = 0.016). In trial 1, lactate concentration in the muscle microdialysate was higher than in blood, indicating lactate production by muscles. This was, however, similar with and without LPS. In trial 2, calculated systemic lactate production increased after LPS (p = 0.031), while lactate clearance remained unchanged. CONCLUSIONS: LPS administration increases lactatemia by increasing lactate production rather than by decreasing lactate clearance. Muscle is, however, unlikely to be a major contributor to this increase in lactate production. TRIAL REGISTRATION: ClinicalTrials.gov NCT01647997.

Low dose of dichloroacetate infusion reduces blood lactate after submaximal exercise in horses

The acute administration of an indirect activator of the enzyme pyruvate dehydrogenase (PDH) in human athletes causes a reduction in blood lactate level during and after exercise. A single IV dose (2.5m.kg-1) of dichloroacetate (DCA) was administered before a submaximal incremental exercise test (IET) with five velocity steps, from 5.0 m.s-1 for 1 min to 6.0, 6.5, 7.0 and 7.5m.s-1 every 30s in four untrained mares. The blood collections were done in the period after exercise, at times 1, 3, 5, 10, 15 and 20 min. Blood lactate and glucose (mM) were determined electro-enzymatically utilizing a YSI 2300 automated analyzer. There was a 15.3% decrease in mean total blood lactate determined from the values obtained at all assessment times in both trials after the exercise. There was a decrease in blood lactate 1, 3, 5, 10, 15 and 20 min after exercise for the mares that received prior DCA treatment, with respective mean values of 6.31±0.90 vs 5.81±0.50, 6.45±1.19 vs 5.58±1.06, 6.07±1.56 vs 5.26±1.12, 4.88±1.61 vs 3.95±1.00, 3.66±1.41 vs 2.86±0.75 and 2.75±0.51 vs 2.04±0.30. There was no difference in glucose concentrations. By means of linear regression analysis, V140, V160, V180 and V200 were determined (velocity at which the rate heart is 140, 160, 180, and 200 beats/minute, respectively). The velocities related to heart rate did not differ, indicating that there was no ergogenic effect, but prior administration of a relatively low dose of DCA in mares reduced lactatemia after an IET.

Determinações e relações dos parâmetros anaeróbios do RAST, do limiar anaeróbio e da resposta lactacidemica obtida no início, no intervalo e ao final de uma partida oficial de handebol

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Feed restriction and a diet's caloric value: The influence on the aerobic and anaerobic capacity of rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Comparação da potência anaeróbia mensurada pelo teste de RAST em diferentes condições de calçado e superfícies

INTRODUÇÃO: O Running Anaerobic Sprint Test (RAST) tem sido considerado um teste válido para avaliação anaeróbia. Entretanto, como a superfície e o calçado podem afetar alguns parâmetros mensurados durante o exercício, isso pode modificar os parâmetros do RAST. OBJETIVO: Comparar as variáveis do RAST mensuradas utilizando chuteiras na grama (RAST CG) e tênis na pista (RAST TP). MÉTODOS: Oito jogadores de futebol (da categoria sub-17) participaram do estudo. Os participantes realizaram dois RAST (intervalo > 24 h). O RAST consistiu em seis corridas máximas de 35m com 10s de intervalo passivo entre cada corrida. O tempo de cada esforço foi registrado para determinação da potência pico (PP), potência média (PM) e índice de fadiga (IF). Após o sexto esforço, amostras sanguíneas foram coletadas para determinação da lactacidemia ([Lac]). RESULTADOS: Durante o RAST TP, a PP (763,1 ± 87,2 W) e PM (621,6 ± 68,1 W) foram significativamente superiores às PP e PM mensuradas em RAST CG (PP = 667,3 ± 67,0 W e PM = 555,9 ± 74,7 W), enquanto que as [Lac] observadas em RAST TP (7,3 ± 1,8 mmol.L-1) foram significativamente inferiores às mensuradas em RAST CG (9,9 ± 3,2 mmol.L-1). No entanto, o IF não foi significativamente diferente (RAST TP = 32,5 ± 8,3%; RAST CG = 34,1 ± 6,6%). Significativas correlações foram observadas entre as PM (r = 0,90) e as [Lac] (r = 0,72). CONCLUSÃO: Podemos concluir que as variáveis do RAST são influenciadas pela superfície e calçado utilizados, com valores superiores observados em RAST TP.

Avaliação da capacidade aeróbia determinada por respostas sanguíneas e ventilatórias em quatro diferentes ergômetros

O objetivo do presente estudo foi comparar as intensidades do ponto de compensação respiratório (PCR), limiar anaeróbio de concentração fixa (OBLA3,5) e limiar anaeróbio de lactato de aumento abrupto lactacidêmico (LAnLAC) determinadas em diferentes ergômetros. Para isso, onze mesatenistas (19±1 anos) realizaram testes incrementais máximos no cicloergômetro, ergômetro de braço, esteira e em teste específico para o tênis de mesa. Durante esses esforços, foram mensuradas as repostas lactacidêmica e respiratória. Na análise intraergômetro, não foram encontradas diferenças significativas entre o PCR, LAnLAC e OBLA3,5 no ergômetro de braço (63,4±4,8W, 66,9±4,5W e 64,5±6,1W, respectivamente), esteira (11,4±0,4km.h-1, 11,3±0,3km.h-1 e 11,1±0,3km.h-1, respectivamente) e teste específico (40,5±1,8bolas.min-1, 42,6±3,6bolas.min-1 e 42,8±5,6bolas.min-1, respectivamente); apenas no cicloergômetro foi verificado menor valor de OBLA3,5 (131,9±6,6W) em relação ao PCR (149,3±4,9W) e o LAnLAC (149,3±4,7W). No entanto, fortes e significativas correlações foram verificadas no teste específico entre todos esses métodos (r entre 0,83 a 0,95), entre o PCR e OBLA3,5 no ergômetro de braço (r=0,78) e entre OBLA3,5 e LAnLAC na esteira (r=0,76). Desse modo, podemos concluir que o PCR, OBLA3,5 e LAnLAC parecem corresponder ao mesmo fenômeno fisiológico, principalmente, no teste específico para o tênis de mesa.

Low dose of dichloroacetate infusion reduces blood lactate after submaximal exercise in horses

The acute administration of an indirect activator of the enzyme pyruvate dehydroge-nase (PDH) in human athletes causes a reduction in blood lactate level during and after exercise. A single IV dose (2.5m.kg-1) of dichloroacetate (DCA) was administered before a submaximal incremental exercise test (IET) with five velocity steps, from 5.0 m.s-1 for 1 min to 6.0, 6.5, 7.0 and 7.5m.s-1 every 30s in four untrained mares. The blood collections were done in the period after exercise, at times 1, 3, 5, 10, 15 and 20 min. Blood lactate and glucose (mM) were determined electro-enzymatically utilizing a YSI 2300 automated analyzer. There was a 15.3% decrease in mean total blood lactate determined from the values obtained at all assessment times in both trials after the exercise. There was a decrease in blood lactate 1, 3, 5, 10, 15 and 20 min after exercise for the mares that received prior DCA treatment, with respective mean values of 6.31±0.90 vs 5.81±0.50, 6.45±1.19 vs 5.58±1.06, 6.07±1.56 vs 5.26±1.12, 4.88±1.61 vs 3.95±1.00, 3.66±1.41 vs 2.86±0.75 and 2.75±0.51 vs 2.04±0.30. There was no difference in glucose concentrations. By means of linear regression analysis, V140, V160, V180 and V200 were determined (velocity at which the rate heart is 140, 160, 180, and 200 beats/minute, respectively). The velocities related to heart rate did not differ, indicating that there was no ergogenic effect, but prior administration of a relatively low dose of DCA in mares reduced lactatemia after an IET.

Acute Phase Responses of Different Positions of High-Goal (Elite) Polo Ponies

The aim of this study was to investigate the acute phase response (APR) in 15 horses by quantifying physiological venous blood variables and serum acute phase proteins (APP) at 5 minutes and 6 and 12 hours after a training match of high-goal polo. The horses were divided into three experimental groups based on their team positions, including defense (n = 6), midfield (n = 5), and attack (n = 4). Serum proteinograms were obtained by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Data were evaluated using analysis of variance for repeated measures. The match represented a high-intensity stimulus for all positions. Defenders appeared to use the anaerobic pathway more than the other positions, as shown by their lower pH and greater lactatemia. Alterations in muscle membrane permeability were observed in all horses, as seen by the increase in serum creatine kinase activity without a correlation with APR. Significant elevations in total serum protein, albumin, ceruloplasmin, haptoglobin, alpha-1 antitrypsin, and 23-kDa protein were seen only during the course of the physical exertion of the match, although there were no differences in these values among positions of the team. After 6 hours of the match, the concentration of transferrin declined, whereas that of alpha-1 acid glycoprotein remained unaltered at all assessed times. These results demonstrated that the defenders required the most use of the anaerobic pathway during the match, and that equestrian polo exercise triggers an acute phase response of relatively short duration; this APR is characterized as noninflammatory, as APR appears to be a physiological alteration related to the stress inherent in physical exercise. © 2013 Elsevier Inc. All rights reserved.

Influência da seleção dos estágios incrementais sobre a intensidade de lactato mínimo: Estudo piloto

The purposes of this study were to assess the influence of stage selection from the incremental phase and the use of peak lactate after hyperlactatemia induction on the determination of the lactate minimum intensity (iLACmin). Twelve moderately active university students (23±5 years, 78.3±14.1 kg, 175.3±5.1 cm) performed a maximal incremental test to determine the respiratory compensation point (RCP) (initial intensity at 70 W and increments of 17.5 W every 2 minutes) and a lactate minimum test (induction with the Wingate test, the incremental test started at 30 W below RCP with increments of 10 W every 3 minutes) on a cycle ergometer. The iLACmin was determined using second order polynomial adjustment applying five exercise stage selection: 1) using all stages (iLACmin P); 2) using all stages below and two stages above iLACminP(iLACminA); 3) using two stages below and all stages above iLACminP(iLACminB); 4) using the largest and same possible number of stages below and above the iLACminP(iLACminI); 5) using all stages and peak lactate after hyperlactatemia induction (iLACminD). No differences were found between the iLACminP(138.2±30.2 W), iLACminA(139.1±29.1 W), iLACminB(135.3±14.2 W), iLACminI(138.6±20.5 W) and iLACmiD(136.7±28.5 W) protocols, and a high level of agreement between these intensities and iLACminPwas observed. Oxygen uptake, heart rate, rating of perceived exertion and lactate corresponding to these intensities was not different and was strongly correlated. However, the iLACminBpresented the lowest success rate (66.7%). In conclusion, stage selection did not influence the determination of iLACmin but modified the success rate. © Creative Commom.

Efeito da luminosidade e do horário do exercício de natação até a exaustão na intensidade de lactato mínimo sobre respostas bioquímicas e hematológicas de ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Caracterização e comparação entre programas de treinamento para cavalos de enduro

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)