Restoration of water and electrolyte balance in horses after repeated exercise in hot and humid conditions

Nine adult riding horses performed on a treadmill a competition exercise test (CET) and 24 h later a standardised exercise test (SET) at mean temperature 28 degrees C and relative humidity 58%. Each horse performed the tests 5 times at 2 week intervals. The horses were given isotonic glucose-electrolyte solution via a nasogastric tube 30 min after the CET, except after the last trial when water was given. Blood lactate, plasma concentration of aldosterone, arginine vasopressin, protein, sodium, potassium, chloride, magnesium and calcium were measured. Heart rate at blood lactate concentration 4 mmol/l (PLa4) in the SET, plasma volume (PV) and red cell volume (CV) were determined. Mean weight loss after CET was 3.1% and did not change significantly during the study. Bodyweight loss (BWL2) before SET (-1.8% after the first trial) decreased linearly with time (P < 0.05) and was -0.8% after the fourth trial. After the fifth trial, when only water was given, the weight loss was -2.5%. PLa4 correlated significantly (P < 0.001) with BWL2 when BWL2 was greater than -1.2%. The horses acclimated to exercise in hot and humid conditions as indicated by better recovery of bodyweight, increased PV, lower peak lactate concentrations and heart rate and attenuated decrease in the concentrations of sodium and chloride. It is concluded that changes in bodyweight provide a good indication of recovery of horses after exercise in hot and humid conditions; and administration of an isotonic glucose-electrolyte rehydration solution after exercise helps to overcome dehydration better than water alone.     

Eosinophilic myopathic syndromes

The purpose of this study was to develop a standardised maximal treadmill exercise test performed until fatigue in order to find reproducible markers for anaerobic metabolism, specifically adenine nucleotide degradation. Six Standardbred trotters performed an incremental maximal treadmill exercise test in 1 min steps (starting with 7 m/s) until they could no longer keep pace with the treadmill. The test was performed twice with at least one week between the tests. Heart rate was recorded and venous blood samples were obtained during the test and in the recovery period for determination of plasma lactate, hypoxanthine, xanthine and uric acid. Muscle biopsy samples (m. gluteus) were collected at rest, immediately post exercise, and after 15 min recovery and analysed for their concentrations of glycogen, creatine phosphate (CP), adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), inosine monophosphate (IMP) and muscle lactate (MLa). Significant decreases in glycogen, CP and ATP and significant increases in IMP and MLa were seen immediately post exercise. None of these metabolites had returned to resting levels after 15 min of recovery. A marked increase in plasma lactate (PLa) occurred during exercise and the peak concentration (mean value = 27.2 mmol/l) was reached within 5 min of recovery. Plasma uric acid concentration did not increase during exercise but rose markedly immediately post exercise, reaching the highest level (mean value = 121.5 micromol/l) at 20-30 min recovery. The duration of the maximal test was related to peak PLa and the uric acid concentration at 30 min of recovery. A correlation was also found between the ATP and IMP concentrations immediately post exercise and the plasma uric acid concentration at 30 min of recovery. The results show that this treadmill test triggered anaerobic metabolism and also that uric acid concentration post exercise seems to be a marker for the adenine nucleotide degradation that occurs during intense exercise. No significant differences were seen in metabolic response between the 2 test occasions.     

Methodology and repeatability of a standardised treadmill exercise test for clinical evaluation of fitness in horses

This paper describes the methodology necessary to perform a clinical exercise test and the expected variability in an individual horse's exercise test measurements based on comparing the results of two repetitions of the test with six horses. The exercise test measurements were obtained with an open flow respiratory gas analysis system, fast time response lactate analyser and an on-board heart rate monitor during an incremental inclined treadmill exercise test. With the exception of peak venous lactate concentration (LACpeak), the results indicate that the mean variability in peak oxygen consumption (VO2peak) peak carbon dioxide production (VCO2peak), peak respiratory exchange ratio (Rpeak), peak heart rate (HRpeak), peak packed cell volume (PCVpeak), peak total plasma protein (TPPpeak) and the maximum number of steps completed during the exercise test (STEPmax) was less than 5 per cent. Variation in the regression analysis of VO2, VCO2 and HR versus velocity was also less than 5 per cent. Slightly higher variation was recorded for LAC and R. Mean variation in the regression analysis of PCV and TPP versus velocity was more than 16 per cent. Mean variation for all of the post exercise test measurements was less than 10 per cent at 1, 5 and 15 mins post exercise. Therefore, the results obtained during a single exercise test are a reliable assessment of a horse's metabolic capability.     

Effects of exogenous hormones and glucose on plasma levels and hepatic metabolism of amino acids in the fetus and in the newborn rat

The present study examines the role of insulin, glucagon and cortisol in the regulation of gluconeogenesis from lactate and amino acids in fetal and newborn rats. Injection of glucagon in the full-term fetal rat caused a rise in glucose (and insulin) and a fall in blood levels of most individual amino acids, stimulated hepatic accumulation of 14C-amino isobutyric acid and 14C-cycloleucine and increased the conversion of 14C lactate, alanine and serine to glucose in vivo and in vitro (liver slices). Such changes were equivalent to the changes seen in 4 h old newborn rats. When glucagon was administered at birth, little difference was observed between control and treated animals in plasma amino acids and a smaller increment in conversion of 14C substrate to glucose occurred. By contrast, insulin injection at birth caused hypoglycemia, suppression of levels of certain amino acids and inhibition of conversion of 14C substrates into glucose. Glucose injection at birth caused elevated glycemia and plasma insulin and suppression of most amino acid levels and of conversion of 14C substrate into glucose. Cortisol injection at birth caused a marked, generalized by hyperaminoacidemia, a stimulation of glucagon secretion and of conversion of 14C substrates into glucose. These observations support the thesis that glucagon plays a major role in the induction of hepatic gluconeogenesis and that insulin acts as an antagonist hormone.     

Comparison of anion gap and strong ion gap as predictors of unmeasured strong ion concentration in plasma and serum from horses

OBJECTIVE: To compare the accuracy of anion gap (AG) and strong ion gap (SIG) for predicting unmeasured strong ion concentration in plasma and serum from horses. ANIMALS: 6 well-trained Standardbred horses undergoing high-intensity exercise (experimental study) and 78 horses and ponies that underwent i.v. administration of lactic acid or endotoxin, and endurance, submaximal, or high-intensity exercise. PROCEDURE: Anion gap was calculated as AG = (Na+ + K+) - (Cl- + HCO3-), and SIG was calculated, using the simplified strong ion model, whereby SIG (mEq/L) = 2.24 x total protein (g/dl)/(1 + 10(6.65-pH)) - AG. The relation between AG or SIG and plasma lactate concentration was evaluated, using linear regression analysis. RESULTS: Linear relations between plasma lactate concentration and AG and SIG were strong for the experimental study (r2 = 0.960 and 0.966, respectively) and the published studies (r2 = 0.914 and 0.925, respectively). The following relations were derived: AG = 1.00 x plasma lactate + 10.5; SIG = 0.99 x plasma lactate + 2.8. An AG > 15 mEq/L indicated an increased unmeasured anion concentration, whereas a SIG < -2 mEq/L indicated an increased unmeasured strong anion concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Anion gap and SIG can be used to predict plasma lactate concentration in horses. AG is accurate and clinically useful for estimating unmeasured strong ion concentration in horses with total protein concentrations within or slightly outside reference range, whereas SIG is more accurate in horses with markedly abnormal total protein concentrations and those of various ages and with various concentrations of albumin, globulin, and phosphate.     

The role of the locus coeruleus and N-methyl-D-aspartic acid (NMDA) and AMPA receptors in opiate withdrawal

The turnover rates of plasma lactate, normalized for O2 consumption rate, are higher in the fetus than in the adult. This occurs despite very low rates of fetal gluconeogenesis which preclude the recycling of lactate carbon into glucose. In an effort to establish the main routes of disposal of fetal plasma lactate, 12 midgestation ovine fetuses (age 74 +/- 1 days) were infused intravenously at constant rate with L-[U-14C]lactate for a 4-hour period. At the end of the infusion, the amounts of 14C retained by the fetus and by the placenta, and the distribution of the retained 14C in free and protein-bound amino acids and in lipids were measured. Of the total 14C infused, 17.0 +/- 1.4% was recovered in the placenta, 4.0 +/- 0.3% in the fetal liver, and 15.0 +/- 0.8% in the extrahepatic fetal tissues. Of the retained radioactive carbon, 45-57% was recovered in the free and protein-bound amino acid fractions and 11-17% in the lipid fractions. Approximately 90% of the 14C in the free amino acid fractions was present as glutamate/glutamine, serine, glycine, and alanine carbon. In conjunction with data on fetal CO2 production from lactate carbon, these results demonstrate that the main routes of fetal lactate disposal are oxidation and synthesis of nonessential amino acids and lipids.     

Utilizing patient satisfaction data to assess quality improvement in community-based medical practices

Effects of a serotonin re-uptake inhibitor and oral amino acid supplementations on physical and mental performance as well as neuroendocrine variables were investigated. 10 male subjects cycled in four trials until exhaustion. Participants ingested a placebo in trial (T) I, 20 mg paroxetine in T II, 21 g branched-chain amino acids (BCAA) in T III and 20g tyrosine (TYR) in T IV. Heart rate, capillary lactate, plasma insulin, free fatty acids, glucose, serotonin and beta-endorphin did not differ in trials. Plasma ammonia increments during exercise were higher in T III. Plasma BCAA in T III and plasma TYR in T IV were increased after 30 min of exercise according to the supplemented substances. In contrast to all other trials, the ratio of plasma free TRP/BCAA did not increase in T III. Plasma TYR/BCAA was augmented in T IV and decreased in T III after 30 min of exercise, whereas it did not change in T I and II. Plasma prolactin (PRL), growth hormone, cortisol, adrenocorticotropic hormone, norepinephrine and epinephrine increased during all trials. Plasma PRL increments were higher in T IV. Exhaustion was reached earlier in T II. No significant differences were found between other trials. Drive during psychometric testing subsequent to exercise was improved in T III and IV. The results indicate that fatigue during endurance exercise was increased by pharmacological augmentation of the brain serotonergic activity. However, a reduction of 5-HT synthesis via BCAA supplementation did not affect physical fatigue. TYR administration did not alter physical performance either although plasma PRL increments suggest that changes in the monoaminergic system were induced. Precaution is necessary before assuming an ergogenic value of amino acids.     

Maternal dietary protein deficiency decreases amino acid concentrations in fetal plasma and allantoic fluid of pigs

This study was conducted to test the hypothesis that maternal dietary protein deficiency decreases amino acid availability to the fetus, thereby contributing to retarded fetal growth. Primiparous gilts selected genetically for low or high plasma total cholesterol concentrations (low line and high line, respectively) were mated, and then fed 1.8 kg/d of isocaloric diets containing 13% or 0.5% crude protein. At d 40 or 60 of gestation, they were hysterectomized, and maternal and fetal blood samples as well as amniotic and allantoic fluids were obtained for analyses of amino acids, ammonia and urea. Dietary protein restriction decreased (P < 0.05) the following: 1) maternal plasma concentrations of urea at d 40 and 60 of gestation; 2) fetal plasma concentrations of alanine, arginine, branched-chain amino acids (BCAA), glutamine, glycine, lysine, ornithine, proline, taurine, threonine and urea at d 60 of gestation; 3) amniotic and allantoic fluid concentrations of urea at d 40 and 60 of gestation; and 4) allantoic fluid concentrations of alanine, arginine, BCAA, citrulline, cystine, glycine, histidine, methionine, proline, serine, taurine, threonine and tyrosine at d 40 of gestation, in gilts of both genetic lines. At d 60 of gestation, protein deficiency decreased (P < 0.05) allantoic fluid concentrations of arginine, cystine, glycine, taurine and tyrosine in low line gilts and of cystine, glutamine, ornithine, serine, taurine and tyrosine in high line gilts. Low line and high line gilts also differed remarkably in allantoic fluid concentrations of arginine, glutamine, ornithine and ammonia at d 40 and 60 of gestation. Our results suggest the following: 1) protein-deficient gilts maintain maternal plasma concentrations of amino acids by mobilizing maternal protein stores and decreasing oxidation of amino acids during the first half of gestation; 2) protein deficiency may impair placental transport of amino acids from the maternal to the fetal blood; and 3) low line and high line gilts differ in fetal amino acid metabolism. Decreases in concentrations of the essential and nonessential amino acids in the fetus may be a mechanism whereby maternal dietary protein restriction results in fetal growth retardation.     

Muscle fiber composition and blood ammonia levels after intense exercise in humans

The relationship between fiber type composition and the increase in blood ammonia was examined following a maximal O2 consumption (VO2max) test. Muscle biopsies were taken from the middle portion of the vastus lateralis for determination of fiber type percentages. Two subject groups were selected on the basis of a high (HST) or low (LST) percentage of slow-twitch fibers and compared for blood ammonia and lactate levels after exercise at work loads of approximately 85 and 110% of VO2max. An inverse relationship was found between the percentage of slow-twitch fibers and the increase in blood ammonia. Blood ammonia increased after exercise at both 85 and 110% of VO2max. However, the increase was twofold greater for the LST group following the 110% work effort. The increases in blood ammonia and lactate were positively correlated for both groups following exercise. The results suggest that the proportion of slow-twitch fibers plays an important role in determining the magnitude of the increase in blood ammonia after intense exercise.     

Ammonia-induced changes in pancreatic hormones and plasma amino acids in patients with liver cirrhosis

The contribution of hyperammonemia to plasma amino acid imbalance in patients with liver disease was assessed in 10 subjects with chronic hepatitis and in 17 advanced cirrhotics. Insulin, glucagon, and plasma amino acids were determined both in the basal state and 45 min after oral ammonium chloride, at doses used in the ammonia-tolerance test. In cirrhotics, ammonia increased to 3 times basal values, in association with a rise in insulin and, more marked, in glucagon. Aromatic amino acids and free tryptophan further increased, while a significant fall in branched-chain amino acids and glutamate was observed. The increase in ammonia levels strongly correlated with the increase in glucagon (r = 0.707). Two patients, with large esophageal varices, showed signs of disturbed consciousness, in association with a marked rise in ammonia and in the ration of free tryptophan to the sum of neutral amino acids. In patients with chronic hepatitis, whose ammonia levels rose slightly, minor variations in pancreatic glucoregulatory hormones and plasma amino acids were observed, as also happened in 10 healthy subjects following ammonium chloride ingestion. Our data fit with the hypothesis that the plasma amino acid imbalance of cirrhotics may be partly due to ammonia-induced changes in pancreatic hormones.     

Metabolic and hemodynamic responses of lower limb during exercise in patients with COPD

Premature lactic acidosis during exercise in patients with chronic obstructive pulmonary disease (COPD) may play a role in exercise intolerance. In this study, we evaluated whether the early exercise-induced lactic acidosis in these individuals can be explained by changes in peripheral O2 delivery (O2). Measurements of leg blood flow by thermodilution and of arterial and femoral venous blood gases, pH, and lactate were obtained during a standard incremental exercise test to capacity in eight patients with severe COPD and in eight age-matched controls. No significant difference was found between the two groups in leg blood flow at rest or during exercise at the same power outputs. Blood lactate concentrations and lactate release from the lower limb were greater in COPD patients at all submaximal exercise levels (all P < 0.05). Leg D02 at a given power output was not significantly different between the two groups, and no significant correlation was found between this parameter and blood lactate concentrations. COPD patients had lower arterial and venous pH at submaximal exercise, and there was a significant positive correlation between venous pH at 40 W and the peak O2 uptake (r = 0.91, P < 0.0001). The correlation between venous pH and peak O2 uptake suggests that early muscle acidosis may be involved in early exercise termination in COPD patients. The early lactate release from the lower limb during exercise could not be accounted for by changes in peripheral O2. The present results point to skeletal muscle dysfunction as being responsible for the early onset of lactic acidosis in COPD.     

Effect of training on some metabolic changes associated with submaximal endurance exercise in the horse

The effects of prolonged cantering before and after a 10 week training programme were studied in 6 horses. Determinations were carried on on venous blood for packed cell volume, glucose, glycerol, free fatty acids, beta-hydroxybutyrate, 11-hydroxycorticosteroids, pH and pCO2. Exercise caused a slight increase in glucose, lactate and pH, a moderate rise in PCV, glycerol and free fatty acids, and a marked rise in 11-hydroxycorticosteroids. A decrease in venous pCO2 occurred and a slight but not significant decrease in beta-hydroxybutyrate. Training was found to cause no significant difference in the changes seen. However, there was a tendency for exercise to result in higher 11-hydroxycorticosteroid levels after training.     

Transport of zwitterionic amino acids in mammalian cells

Amino acid transport is an important metabolic process that regulates the amino acid flux between the extracellular and intracellular space of the cell. Amino acids enter to the cell through plasmatic membrane proteins that have been kinetically well characterized. System A is involved in the transport of zwitterionic amino acids with short lateral chains and plays a key role in the gluconeogenesis from amino acids, especially from alanine, and has been implicated in the process of cellular duplication. System N transports amino acids with a nitrogen side chain, specially glutamine, an important regulator of protein synthesis. System L allows the entrance of zwitterionic amino acids with large side chains: it is normally constitutive and it is important for the uptake of these amino acids into the brain where some of them are precursors of neurotransmitters. Amino acid transport has been studied at a molecular level since several cDNAs have been cloned opening the possibility to study their structure and regulation. Several isoforms of some zwitterionic amino acids have been cloned including systems ASC, Gly, beta and proline, which have been classified as a superfamily of carrier proteins containing 6 to 12 spanning membrane domains. This review shows the general aspects of amino acid transport and recent advances in the zwitterionic amino acid transport systems, emphasizing the molecular characteristics of cloned systems and their regulatory factors.     

Protection of residents in the vicinity of intensive livestock units from possible health risks

To assess whether hormone and metabolic responses in an upright bicycle exercise test are equivalent for subjects with different physical characteristics if test duration for reaching individual maximal work capacity (PWCmax) is standardized we investigated plasma catecholamines, human atrial natriuretic peptide (hANP) and blood lactate responses in twenty healthy sedentary subjects. Ten male (38.5 +/- 4.7 yrs) and ten female (34.5 +/- 6.4 yrs) healthy volunteers performed two ergometries, a first one with incremental steps of 25 Watts each for two minutes to determine PWCmax, and a second one with incremental steps of PWCmax/6. According to this definition a test duration of 12 min was attained for all subjects for the second ergometry. The results show that the increase of the rate pressure product (RPP) as an index of relative cardiac work is significantly different between the male and female group in the test with constant 25 Watts steps. But with the modified exercise test RPP/time-slopes are nearly identical, identicating equivalent cardiac work due to gender and body surface. Similar results are obtained for plasma catecholamines, hANP and blood lactate. Mean values did not differ in the modified exercise test between the male and female group either in the sub-maximal range or at PWCmax. In conclusion, our data suggest that in a maximal exercise test with equal test duration, and considering individual physical properties for the calculation of incremental steps hormonal and metabolic responses are equivalent. It seems that the designed, modified exercise test provides inter-individual comparisons at least for these investigated parameters. The test may be helpful if catecholamines, hANP or lactate are used as diagnostic parameters in patients.     

Plasma cyclic AMP and blood lactate responses to incremental cycling in untrained male subjects

Recently, it has been suggested that epinephrine influences blood lactate and the lactate threshold during incremental exercise through a beta-adrenergic adenylate cyclase dependent mechanism. We sought to characterize the relationship between the changes in the beta-adrenergic adenylate cyclase system and blood lactate during incremental exercise indirectly through the measurement of plasma cAMP. The relationships of plasma cAMP to blood lactate levels and the lactate threshold were examined in nine untrained male subjects. Each subject performed an incremental exercise test to volitional exhaustion on an electronically-braked cycle ergometer. Although plasma cAMP was rising at the lactate threshold, it did not demonstrate the classic threshold response usually seen in blood lactate. Pairwise matched t-tests were used as a post-hoc test to determine if the successive changes in blood lactate and plasma cAMP between 21.4, 38.6, 58.7, 81.2 and 100% of VO2max were significant. Plasma cAMP was rising between 38.6% and 58.7% and between 58.7% and 81.2% of VO2max, but these changes in plasma cAMP did not reach statistical significance (p > 0.0125) with Bonferoni adjustment. The change in plasma cAMP compared to its previous value as well as the change in plasma cAMP above the resting value was not statistically significant until 81.2% of VO2max. A moderate but significant correlation was observed between blood lactate and plasma cAMP levels (r = 0.612) using blood samples obtained at each workstage in all subjects. The mean correlation between blood lactate and plasma cAMP was 0.75 (S.E. = 0.05) and ranged between 0.58 and 0.97 in individual subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stoichiometry, kinetics, and regulation of glucose and amino acid metabolism of a recombinant BHK cell line in batch and continuous cultures

Batch and continuous cultures were carried out to study the stoichiometry, kinetics, and regulation of glucose and amino acid metabolism of a recombinant BHK cell line, with particular attention to the metabolism at low levels of glucose and glutamine. The apparent yields of cells on glucose and glutamine, lactate on glucose, and ammonium on glutamine were all found to change significantly at low residual concentrations of glucose (< 5 mmol/L) and glutamine (< 1 mmol/L). The uptake rates of glucose and glutamine were markedly reduced at low concentrations, leading to a more effective utilization of these nutrients for energy metabolism and biosynthesis and reduced formation rates of lactate and ammonium. However, the consumption of other amino acids, especially the essential amino acids leucine, isoleucine, and valine and the nonessential amino acids serine and glutamate, was strongly enhanced at low glutamine concentration. Quantitatively, it was shown that the cellular yields and rates associated with glucose metabolism were primarily determined by the residual glucose concentration, while those associated with glutamine metabolism depended mainly on the residual glutamine. Both experimental results and analysis of the kinetic data with models showed that the glucose metabolism of BHK cells is not affected by glutamine except for a slight influence under glucose limitation and glutaminolysis not by glucose, at least not significantly under the experimental conditions. Compared to hybridoma and other cultured animal cells, the recombinant BHK cell line showed remarkable differences in terms of nutrient sensitivity, stoichiometry, and amino acid metabolism at low levels of nutrients. These cell-line-specific stoichiometry and nutrient needs should be considered when designing an optimal medium and/or feeding strategy for achieving high cell density and high productivity of BHK cells. In this work, a cell density of 1.1 x 10(7) cells/mL was achieved in a conventional continuous culture by using a proper feed medium.     

Influence of the nitrogen source on Saccharomyces cerevisiae anaerobic growth and product formation

To prevent the loss of raw material in ethanol production by anaerobic yeast cultures, glycerol formation has to be reduced. In theory, this may be done by providing the yeast with amino acids, since the de novo cell synthesis of amino acids from glucose and ammonia gives rise to a surplus of NADH, which has to be reoxidized by the formation of glycerol. An industrial strain of Saccharomyces cerevisiae was cultivated in batch cultures with different nitrogen sources, i.e., ammonium salt, glutamic acid, and a mixture of amino acids, with 20 g of glucose per liter as the carbon and energy source. The effects of the nitrogen source on metabolite formation, growth, and cell composition were measured. The glycerol yields obtained with glutamic acid (0.17 mol/mol of glucose) or with the mixture of amino acids (0.10 mol/mol) as a nitrogen source were clearly lower than those for ammonium-grown cultures (0.21 mol/mol). In addition, the ethanol yield increased for growth on both glutamic acid (by 9%) and the mixture of amino acids (by 14%). Glutamic acid has a large influence on the formation of products; the production of, for example, alpha-ketoglutaric acid, succinic acid, and acetic acid, increased compared with their production with the other nitrogen sources. Cultures grown on amino acids have a higher specific growth rate (0.52 h-1) than cultures of both ammonium-grown (0.45 h-1) and glutamic acid-grown (0.33 h-1) cells. Although the product yields differed, similar compositions of the cells were attained. The NADH produced in the amino acid, RNA, and extracellular metabolite syntheses was calculated together with the corresponding glycerol formation. The lower-range values of the theoretically calculated yields of glycerol were in good agreement with the experimental yields, which may indicate that the regulation of metabolism succeeds in the most efficient balancing of the redox potential.     

Lactic acid does not directly activate hypothalamic-pituitary corticotroph function

The role that metabolic products play in regulating the hypothalamic-pituitary-adrenal (HPA) axis during strenuous exercise is speculative. This investigation examined the extent to which lactic acid, a major metabolite of anaerobic exercise, directly affects hypothalamic-pituitary function. Specifically, beta-endorphin secretion was measured from AtT-20 (D-16) mouse corticotroph tumor cells treated either acutely (15 min - 180 min) or chronically (1 day - 3 day) with physiologic levels of lactate (0. 5 x 10-3 M to 5 x 10-2 M) or lactate in combination with the corticotroph releasing factors: corticotroph releasing hormone (CRH), arginine vasopressin (AVP), norepinephrine and/or epinephrine. Findings with AtT-20 cell cultures were shown to be representative of responses in primary cultures of rat anterior pituitary. Lactic acid did not alter the spontaneous release of beta-endorphin by AtT-20 cells under either acute or chronic conditions. While CRH, norepinephrine, and epinephrine evoked significant increases in beta-endorphin release, lactate, in combination with these secretagogues did not alter their effects. Similarly, lactic acid failed to alter basal or stimulated release of beta-endorphin by primary cultures of rat anterior pituitary. The addition of lactate (3 x 103 M) to rat hypothalamic explants did, however, produce a modest but significant reduction in spontaneous CRH release, suggesting that lactate may facilitate the return to basal secretion following exercise. The present findings show that physiologic concentrations of lactate have no effect, either alone or in combination with other pituitary secretagogues, on corticotroph secretion. Whereas a physiologic action for lactate within the hypothalamus is possible, the present findings indicate that lactate is an inhibitor of CRH release. Thus, lactate does not appear to play a direct role in the profound activation of the HPA axis that occurs in response to strenuous exercise.     

First total synthesis of ganglioside GT1a alpha

Controversy still exists concerning the potential ergogenic benefit of caffeine (CAF) for exercise performance. The purpose of this study was to compare the effects of CAF ingestion on endurance performance during exercise on a bicycle ergometer at two different intensities, i.e., approximately 10% below and 10% above the anaerobic threshold (AT). Eight untrained males, non-regular consumers of CAF, participated in this study. AT, defined as the intensity (watts) corresponding to a lactate concentration of 4 mM, was determined during an incremental exercise test from rest to exhaustion on an electrically braked cycle ergometer. On the basis of these measurements, the subjects were asked to cycle until exhaustion at two different intensities, i.e., approximately 10% below and 10% above AT. Each intensity was performed twice in a double-blind randomized order by ingesting either CAF (5 mg/kg) or a placebo (PLA) 60 min prior to the test. Venous blood was analyzed for free fatty acid, glucose, and lactate, before, during, and immediately after exercise. Rating of perceived exertion and time to exhaustion were also measured during each trial. There were no differences in free fatty acids or lactate levels between CAF and PLA during and immediately after exercise for either intensity. Immediately after exercise glucose increased in the CAF trial at both intensities. Rating of perceived exertion was significantly lower (CAF = 14.1 +/- 2.5 vs PLA = 16.6 +/- 2.4) and time to exhaustion was significantly higher (CAF = 46.54 +/- 8.05) min vs PLA = 32.42 +/- 14.81 min) during exercise below AT with CAF. However, there was no effect of CAF treatment on rating of perceived exertion (CAF = 18.0 +/- 2.7 vs PLA = 17.6 +/- 2.3) and time to exhaustion (CAF = 18.45 +/- 7.28 min vs PLA = 19.17 +/- 4.37 min) during exercise above AT. We conclude that in untrained subjects caffeine can improve endurance performance during prolonged exercise performed below AT and that the decrease of perceived exertion can be involved in this process.