Effect of cold air inhalation on core temperature in exercising subjects under heat stress

Whether increasing respiratory heat loss (RHL) during exercise under heat stress can contain elevation of rectal temperature (Tre) was examined. Eight men cycled twice at 45-50% their maximum work rate until exhaustion at ambient temperature and relative humidity of 38 degrees C and 90-95%, respectively. They inspired either cold (3.6 degrees C) or ambient air in random sequence. When subjects breathed cold air during 23 min of exercise, a ninefold increase in RHL was observed vs. similar work during hot air inhalation (32.81 vs. 3.46 W). Respiratory frequency (f) and rate of rise in Tre decreased significantly (P less than or equal to 0.004 and P less than or equal to 0.002, respectively). The rise in skin temperature in each inhalant gas condition was accompanied by a parallel almost equal increase in core temperature above basal (delta Tre) for equivalent gains in skin temperature. The increase in tidal volume and decreased f in the cold condition allowed more effective physical conditioning of cold inspirate gas in the upper airways and aided RHL. Cold air inhalation also produced a significant (P less than or equal to 0.05) decrease in heart rate vs. hot air inhalation in the final stages of exercise. Insignificant changes in O2 consumption and total body fluid loss were found. These data show that cold air inhalation during exercise diminishes elevation of Tre and suggest that both the intensity and duration of work can thus be extended. The importance of the physical exchange of heat energy and any physiological mechanisms induced by the cold inspirate in producing the changes is undetermined.     

Tissue ammonia and amino acids in rats at various oxygen pressures

The amino acid and ammonia profiles in various tissues of the rat exposed to different pressures of pure oxygen have been studied. Well-defined changes in behavioral activity accompanied a profile of increasing pressure, culminating in convulsive activity in each group of exposed animals. After an initial depression of ammonia, in all tissues studied at 0.68 atm oxygen ammonia increased significantly at higher oxygen pressures. A rise in tissue ammonia took place in the absence of undue muscular activity on the part of the exposed animals. A significant increase in ammonia occurred first in brain and liver at 3.40 atm. Ammonia concentration was high in all tissues after convulsions occurred at 4.08 atm. Between 0.68 and 2.72 atm oxygen, tissue ammonia concentration was generally low and brain glutamate and gamma-aminobutyric acid were high. At pressures higher than 2.72 atm oxygen, tissue glutamate declined and glutamine increased. Alanine became significantly elevated in serum and muscle at high oxygen pressure, and aspartate was depressed in heart, liver, and muscle. These pressure-course experiments on ammonia accumulation in tissue confirm previous serial time course observations that ammonia accumulates in the brain and several tissues of the rat even in the absence of undue muscular activity during high-pressure oxygen exposure and is a significant factor in inducing convulsions.     

The time course of brain and blood catecholamines, catechol O-methyltransferase, and amino acids in rats convulsed by oxygen at high pressure.

The time course of changes in blood and brain catecholamines, catechol O-methyltransferase (COMT), ammonia, and amino acids leading to convulsion by high pressure oxygen breathing (OHP) in rats has been investigated. Brain catecholamines were suppressed by OHP. They changed in phase with brain COMT concentration and consequently were not due to the action of this degrading enzyme. Convulsive actions seem not to be influenced by brain catecholamine concentration. Blood adrenaline concentrations are, however, significantly elevated both prior to and during convulsions. In both brain and blood, ammonia concentration increases, glutamate decreases, and glutamine-aspargine increases. It is proposed that the efficacy of the glutamate-glutamine ammonia buffering system in blood and brain is important in the prevention of the onset of convulsions but that when brain gamma-aminobutyric acid is depressed to critical levels, convulsions result.     

Revisiting the use of Iprodione and Trichoderma in the integrated management of onion white rot

The biocontrol properties of Trichoderma species are well documented, but their effectiveness in antagonism of the problematic Sclerotium cepivorum, the causal agent of white rot in Allium species, appears limited with reports of significant control only relating to deliberately-mutated strains of Trichoderma. Our previous studies have indicated the possibility of using selected naturally-occurring strains of the antagonist in the suppression of other diseases; now in vitro and controlled environment in vivo studies have indicated that a degree of control of Onion White Rot is possible, and that the selected antagonist strains can be used in integrated treatments with Iprodione to good effect. The possible value of such treatments is considered in light of other approaches to the suppression of this continuing problem.     

Training theory and taper: validation in triathlon athletes

This paper defines a training theory with which to predict the effectiveness of various formats of taper in optimizing physical performance from a standardized period of training and taper. Four different taper profiles: step reduction vs exponential (exp) decay and fast vs slow exp decay tapers, were simulated in a systems model to predict performance p(t) resulting from a standard square-wave quantity of training for 28 days. The relative effectiveness of each of the profiles in producing optimal physical improvement above pre-taper criterion physical test standards (running and cycle ergometry) was determined. Simulation showed that an exp taper was better than a step-reduction taper, and a fast exp decay taper was superior to a slow exp decay taper. The results of the simulation were tested experimentally in field trials to assess the correspondence between simulation and real-training criterion physical tests in triathlon athletes. The results showed that the exp taper (tau = 5 days) group made a significantly greater improvement above a pre-taper standard (P < or = 0.05) than the step-reduction taper group in cycle ergometry, and was better, but not significantly so, in a 5-km run. A fast exp taper group B (tau = 4 days) performed significantly better (P < or = 0.05) in maximal, cycle ergometry above a pre-taper training standard than a slow exp taper group A (tau = 8 days) and was improved more, but not significantly so, than group A in a 5-km criterion run. The mean improvement on both physical tests by exp decay taper groups all increased significantly (P < or = 0.05) above their pre-taper training standard. Maximum oxygen uptake increased significantly in a group of eight remaining athletes during 2 weeks of final taper after three athletes left early for final preparations at the race site.     

Effects of PKC isozyme inhibitors on constrictor responses in the feline pulmonary vascular bed

The effects of G?-6976, a Ca(2+)-dependent protein kinase C (PKC) isozyme inhibitor, and rottlerin, a PKC-delta isozyme/calmodulin (CaM)-dependent kinase III inhibitor, on responses to vasopressor agents were investigated in the feline pulmonary vascular bed. Injections of angiotensin II, norepinephrine (NE), serotonin, BAY K 8644, and U-46619 into the lobar arterial constant blood flow perfusion circuit caused increases in pressure. G?-6976 reduced responses to angiotensin II; however, it did not alter responses to serotonin, NE, or U-46619, whereas G?-6976 enhanced BAY K 8644 responses. Rottlerin reduced responses to angiotensin II and NE, did not alter responses to serotonin or U-46619, and enhanced responses to BAY K 8644. Immunohistochemistry of feline pulmonary arterial smooth muscle cells demonstrated localization of PKC-alpha and -delta isozymes in response to phorbol 12-myristate 13-acetate and angiotensin II. Localization of PKC-alpha and -delta isozymes decreased with administration of G?-6976 and rottlerin, respectively. These data suggest that activation of Ca(2+)-dependent PKC isozymes and Ca(2+)-independent PKC-delta isozyme/CaM-dependent kinase III mediate angiotensin II responses. These data further suggest that Ca(2+)-independent PKC-delta isozyme/CaM-dependent kinase III mediate responses to NE. A rottlerin- or G?-6976-sensitive mechanism is not involved in mediating responses to serotonin and U-46619, but these PKC isozyme inhibitors enhanced BAY K 8644 responses in the feline pulmonary vascular bed.     

A spatiotemporal characterization of the effect of p53 phosphorylation on its interaction with MDM2

The interaction of p53 and MDM2 is modulated by the phosphorylation of p53. This mechanism is key to activating p53, yet its molecular determinants are not fully understood. To study the spatiotemporal characteristics of this molecular process we carried out Brownian dynamics simulations of the interactions of the MDM2 protein with a p53 peptide in its wild type state and when phosphorylated at Thr18 (pThr18) and Ser20 (pSer20). We found that p53 phosphorylation results in concerted changes in the topology of the interaction landscape in the diffusively bound encounter complex domain. These changes hinder phosphorylated p53 peptides from binding to MDM2 well before reaching the binding site. The underlying mechanism appears to involve shift of the peptide away from the vicinity of the MDM2 protein, peptide reorientation, and reduction in peptide residence time relative to wild-type p53 peptide. pThr18 and pSr20 p53 peptides experience reduction in residence times by factors of 13.6 and 37.5 respectively relative to the wild-type p53 peptide, indicating a greater role for Ser20 phosphorylation in abrogating p53 MDM2 interactions. These detailed insights into the effect of phosphorylation on molecular interactions are not available from conventional experimental and theoretical approaches and open up new avenues that incorporate molecular interaction dynamics, for stabilizing p53 against MDM2, which is a major focus of anticancer drug lead development.     

Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta

Birthweight has been associated with a number of health outcomes throughout life. Crucial to proper infant growth and development is the placenta, and alterations to placental gene function may reflect differences in the intrauterine environment which functionally contribute to infant growth and may ultimately affect the child''s health. To examine if epigenetic alteration to the glucocorticoid receptor (GR) gene was linked to infant growth, we analyzed 480 human placentas for differential methylation of the GR gene exon 1F and examined how this variation in methylation extent was associated with fetal growth. Multivariable linear regression revealed a significant association (p < 0.0001) between differential methylation of the GR gene and large for gestational age (LGA) status. Our work is one of the first to link infant growth as a measure of the intrauterine environment and epigenetic alterations to the GR and suggests that DNA methylation may be a critical determinant of placental function.Key words: DNA methylation, placenta, fetal development, birthweight, epigenetics