Effect of glutamine supplementation on exercise-induced changes in lymphocyte function

The purpose of this study was toinvestigate the possible role of glutamine in exercise-inducedimpairment of lymphocyte function. Ten male athletesparticipated in a randomized, placebo-controlled, double-blindcrossover study. Each athlete performed bicycle exercise for 2 hat 75% of maximum O₂ consumption on 2 separate days.Glutamine or placebo supplements were given orally during and up to2 h postexercise. The trial induced postexercise neutrocytosisthat lasted at least 2 h. The total lymphocyte count increased bythe end of exercise due to increase of bothCD3⁺TCR⁺ andCD3⁺TCR⁺ T cells as well asCD3CD16⁺CD56⁺ naturalkiller (NK) cells. Concentrations of CD8⁺ andCD4⁺ T cells lacking CD28 and CD95 on their surfaceincreased more than those of cells expressing these receptors. Withinthe CD4⁺ cells, only CD45RA memory cells, butnot CD45RA⁺ naive cells, increased in response to exercise.Most lymphocyte subpopulations decreased 2 h after exercise.Glutamine supplementation abolished the postexercise decline in plasmaglutamine concentration but had no effect on lymphocyte trafficking, NKand lymphokine-activated killer cell activities, T cell proliferation,catecholamines, growth hormone, insulin, or glucose. Neutrocytosis wasless pronounced in the glutamine-supplemented group, but it is unlikelythat this finding is of any clinical significance. This study does notsupport the idea that glutamine plays a mechanistic role inexercise-induced immune changes.

     

Structural evidence for ligand specificity in the binding domain of the human androgen receptor. Implications for pathogenic gene mutations

The crystal structures of the human androgen receptor (hAR) and human progesterone receptor ligand-binding domains in complex with the same ligand metribolone (R1881) have been determined. Both three-dimensional structures show the typical nuclear receptor fold. The change of two residues in the ligand-binding pocket between the human progesterone receptor and hAR is most likely the source for the specificity of R1881 to the hAR. The structural implications of the 14 known mutations in the ligand-binding pocket of the hAR ligand-binding domains associated with either prostate cancer or the partial or complete androgen receptor insensitivity syndrome were analyzed. The effects of most of these mutants could be explained on the basis of the crystal structure.     

Theromin, a novel leech thrombin inhibitor

We purified the most potent thrombin inhibitor described to date from the rhynchobdellid leech Theromyzon tessulatum. Designated theromin, it was purified to apparent homogeneity by gel permeation and anion exchange chromatography followed by two reverse-phase steps of high performance liquid chromatography. The primary sequence of theromin (a homodimer of 67 amino acid residues including 16 cysteine residues) was determined by a combination of reduction and s-beta-pyridylethylation, Edman degradation, trypsin enzymatic digestion, and matrix-assisted laser desorption mass spectrometry measurement. Theromin exhibits no sequence homology with any other thrombin inhibitors. Furthermore, theromin significantly diminishes, in a dose-dependent manner, the level of human granulocyte and monocyte activation induced by lipopolysaccharides. In summary, this potent thrombin inhibitor promises to have high biomedical significance.     

Effects of lairage temperature and holding time on pig behaviour and on carcass and meat quality

Twenty three groups of about 30 pigs each were kept in an environmentally controlled room in lairage, at temperatures of 20 or 35°C for periods of 0.5 or 3 h, to establish the effects of these parameters on animal behaviour and meat quality. Following initial exploration, 50% of pigs kept at 35°C but only 5% kept at 20°C lay down before the end of the 0.5 h period. Seven percent of pigs fought in both temperature conditions. When held in lairage for 0.5 h there was no difference in meat quality or skin damage at either temperature. When held for 3 h, about 95% of pigs were lying down after 2 h in the pens. Again, the percentage of animals fighting was similar for both temperatures, the number of encounters increasing during the first 30–40 min. The more intense initial fighting within the group held at 35°C resulted in the pigs lying down slightly earlier. Irrespective of the lairage time, the frequency of sexual activity decreased with temperature. The proportion of carcasses with skin damage increased with lairage time due, perhaps, to the longer duration of aggressive encounters. Increased lairage time at 20°C reduced the incidence of PSE meat, but at 35°C the longer lairage time showed no benefit to animal welfare or meat quality.     

A Four-Compartment Metabolomics Analysis of the Liver,Muscle, Serum,and Urine Response to Polytrauma with Hemorrhagic Shock following Carbohydrate Prefeed

Objective

Hemorrhagic shock accompanied by injury represents a major physiologic stress. Fasted animals are often used to study hemorrhagic shock (with injury). A fasted state is not guaranteed in the general human population. The objective of this study was to determine if fed animals would exhibit a different metabolic profile in response to hemorrhagic shock with trauma when compared to fasted animals.

Methods

Proton (1H) NMR spectroscopy was used to determine concentrations of metabolites from four different compartments (liver, muscle, serum, urine) taken at defined time points throughout shock/injury and resuscitation. PLS-DA was performed and VIP lists established for baseline, shock and resuscitation (10 metabolites for each compartment at each time interval) on metabolomics data from surviving animals.

Results

Fed status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The death rate for CPF animals is higher than FS animals (47 vs 28%). The majority of deaths occur post-resuscitation suggesting reperfusion injury. The metabolomics response to shock reflects priorities evident at baseline. FS animals raise the baseline degree of proteolysis to provide additional amino acids for energy production while CPF animals rely on both glucose and, to a lesser extent, amino acids. During early resuscitation levels of metabolites associated with energy production drop, suggesting diminished demand.

Conclusions

Feeding status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The response to shock reflects metabolic priorities at baseline.     

A single dose of S‐ketamine induces long‐term antidepressant effects and decreases oxidative stress in adulthood rats following maternal deprivation

Ketamine, an antagonist of N‐methyl‐d ‐aspartate receptors, has produced rapid antidepressant effects in patients with depression, as well as in animal models. However, the extent and duration of the antidepressant effect over longer periods of time has not been considered. This study evaluated the effects of single dose of ketamine on behavior and oxidative stress, which is related to depression, in the brains of adult rats subjected to maternal deprivation. Deprived and nondeprived Wistar rats were divided into four groups nondeprived + saline; nondeprived + S‐ketamine (15 mg/kg); deprived + saline; deprived + S‐ketamine (15 mg/kg). A single dose of ketamine or saline was administrated during the adult phase, and 14 days later depressive‐like behavior was assessed. In addition, lipid damage, protein damage, and antioxidant enzyme activities were evaluated in the rat brain. Maternal deprivation induces a depressive‐like behavior, as verified by an increase in immobility and anhedonic behavior. However, a single dose of ketamine was able to reverse these alterations, showing long‐term antidepressant effects. The brains of maternally deprived rats had an increase in protein oxidative damage and lipid peroxidation, but administration of a single dose of ketamine reversed this damage. The activities of antioxidant enzymes superoxide dismutase and catalase were reduced in the deprived rat brains. However, ketamine was also able to reverse these changes. In conclusion, these findings indicate that a single dose of ketamine is able to induce long‐term antidepressant effects and protect against neural damage caused by oxidative stress in adulthood rats following maternal deprivation. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1268–1281, 2015