Ammonia metabolism during exercise in man

Physical exercise is accompanied by increased plasma levels of ammonia but it is not known whether this rise primarily reflects accelerated formation in muscle or decreased removal by the liver. Consequently, leg and splanchnic exchange of ammonia was examined, using the catheter technique, in 11 healthy subjects at rest, during three consecutive 15 min periods of bicycle exercise at gradually increasing work loads (35%, 55% and 80% of maximum oxygen uptake) and for 60 min during post-exercise recovery. The basal arterial ammonia level was 22 +/- 2 mumol/l, the concentration rose curvilinearly in response to increasing work loads (peak value 84 +/- 12 mumol/l), and fell rapidly after exercise, reaching basal levels after 30-60 min. A linear regression was found for ammonia levels in relation to lactate concentrations at rest and during exercise (r = 0.85, P less than 0.001). A significant relationship was also observed between arterial ammonia and alanine levels (r = 0.75, P less than 0.001). Leg tissues showed a net uptake of ammonia in the basal state (2.4 +/- 0.5 mumol/min). During exercise this changed to a net production, which increased curvilinearly with rising work intensity (peak value 46 +/- 15 mumol/min) but reverted to a net ammonia uptake at 30-60 min after exercise. Splanchnic ammonia uptake (basal 12 +/- 2 mumol/min) did not change in response to exercise but increased transiently during the early post-exercise period. From the above observations we conclude that the hyperammonaemia of exercise comes primarily from muscle release, while the splanchnic removal of ammonia is essentially unaltered. Part of the ammonia formed in contracting muscle is most likely used in the synthesis of amino acids, mainly glutamine and probably alanine.     

Increase in plasma ammonia and amino acids when rats are fed a 44% casein diet

Rats were trained to eat a 6% casein basal diet during a 3-hour period per day. They were then fed either the same 6% casein diet or a 44% casein diet for 3 hours. No food intake depression was observed in the rats eating 44% casein diet during the 3-hour period. Plasma ammonia and amino acids and brain amino acids were measured at 0, 4, 12 and 24 hours after presentation of the 6% or 44% casein diets. Plasma ammonia rose to 134 (p less than 0.01) and 110 micromolar (p less than 0.05) in the 44% casein fed rats at 4 and 12 hours, respectively, as compared to 67 and 53 micromolar, respectively, for the 6% casein fed rats. All plasma amino acid concentrations except methionine and glutamate were elevated (p less than 0.05) at 4 hours. In the brain, threonine, glutamine and tyrosine concentrations were elevated (p less than 0.05) at 4 hours after diet presentation. At 24 hours, valine, isoleucine, leucine, phenylalanine, and methionine concentrations were also elevated (p less than 0.05). Because intake of the 44% casein diet decreases the second day of its presentation, as noted in an earlier experiment, the increases in plasma ammonia and its possible entry into the brain as reflected by increased brain glutamine together with changes in amino acid concentrations should be considered collectively among possible metabolic signals affecting intake of high protein diets.     

Effects of adrenaline and prior exercise on the release of alanine, glutamine and glutamate from incubated rat skeletal muscle

Catecholamines have been proposed as important regulators of the rate of amino acid release from skeletal muscle. In the present study, we have investigated the influence of adrenergic action and its possible interaction with exercise on muscle release and tissue content of alanine, glutamine and glutamate. For this purpose epitrochlearis muscles were dissected from resting and exercised (1 and 2 h) rats and incubated for 1 h in the presence or absence of adrenaline. In addition, muscles from water-immersed resting rats were included to separate the influence of the stress involved in the swimming exercise from that of muscle contractile activity per se. In muscles from untreated resting rats, the release, tissue content and total amount (released amount + tissue content) of the three amino acids were not influenced by 10(-7) M adrenaline; when the adrenaline concentration was raised to 10(-5) M only the tissue content of glutamate was significantly changed (-50%, P less than 0.001). However, in muscles of rats subjected to 2 h prior exercise or water immersion, 10(-7) M adrenaline significantly increased the release of glutamine (+ 48% and +34%, P less than 0.05) and glutamate (+38% and +27%, P less than 0.05). Moreover, 1 h of water immersion resulted in a significant increase in muscle glutamine and glutamate compared to values from the exercised and control rats. The data suggest that adrenergic action is involved in the regulation of muscle amino acid transport during exercise and that the stress involved in exercise may mask the influence of contractile activity per se on formation of amino acids in skeletal muscle.     

Muscle ammonia and amino acid metabolism during dynamic exercise in man

The effect of dynamic exercise on muscle and blood ammonia (NH3) and amino acid contents has been investigated. Eight healthy men cycled at 50% and 97% of maximal oxygen uptake for 10 min and 5.2 min (to fatigue), respectively. Biopsies (quadriceps femoris muscle), arterial and femoral venous blood samples were obtained at rest and during exercise. Muscle NH3 at rest and after submaximal exercise was (means +/- SE) 0.5 +/- 0.1 mmol/kg dry muscle (d.m.) and increased to 4.1 +/- 0.5 mmol/kg d.m. at fatigue (P less than 0.001). The total adenine nucleotide (TAN) pool (TAN = ATP + ADP + AMP) did not change after submaximal exercise but decreased significantly at fatigue (P less than 0.001). The decrease in TAN was similar to the increase in NH3. Muscle lactate was 3 +/- 1 mmol/kg d.m. at rest and increased to 104 +/- 5 mmol/kg d.m. at fatigue. Whole blood and plasma NH3 did not change significantly during submaximal but both increased significantly during maximal exercise (P less than 0.001). During maximal exercise the leg released 7,120 mumol/min of lactate, whereas only 89 mumol/min of NH3 were released. NH3 accumulation in muscle could buffer only 3% of the hydrogen ions released from lactate, and NH3 release could account for only 1% of the net hydrogen ion transport out of the cell. Muscle glutamine was constant throughout the study, whereas glutamate decreased and alanine increased during exercise (P less than 0.001). No significant changes in either arterial whole blood glutamine or glutamate were observed. Arterial plasma glutamine and glutamate concentrations, however, increased and decreased (P less than 0.001), respectively, during exercise. It is concluded that (1) muscle and blood NH3 levels increase only during strenuous exercise and (2) NH3 accumulation is of minor importance for regulating acid-base balance in body fluids during exercise.     

Stress hormones initiate prolonged changes in the muscle amino acid pattern.

Eight healthy volunteers were given an infusion containing cortisol, glucagon and adrenaline during 6 h. Muscle biopsies were taken before and at 6, 12 and 24 h. During the infusion serum cortisol, glucagon, glucose and insulin were increased. The stress hormone infusion induced characteristic changes in the muscle and plasma amino acid patterns similar to those seen early in protein catabolism. Muscle glutamine decreased at 12 and 24 h by -18.2 +/- 3.8 and -28.8 +/- 4.8%, respectively. The branched chain amino acids decreased at 6 h by -54.6 +/- 4.2% while increased levels (by 54.7 +/- 13.1%) were seen at 24 h. Plasma amino acids decreased during the infusion period and returned to basal during the postinfusion period. Despite a short-term infusion during 6 h the muscle amino acid pattern was still affected at 12 and 24 h and some of the changes were more accentuated at those timepoints as compared with the changes seen at 6 h.     

Alternative pathway activation of complement in laparoscopic and open rectal surgery

The study was designed to investigate whether complement is activated in patients subject to rectal surgery and whether the choice of surgical technique (open or laparoscopic) has any impact on the activation of complement. Our hypothesis is that laparoscopic surgery leads to a lower-level activation of complement than open surgery. Patients (n = 24) subject to rectal surgery owing to rectal cancer were included. The study was prospective and randomized. The patients were randomized to either laparoscopic surgery (n = 12) or open surgery (n = 12). Blood samples for determination of complement activation (C4d, Bb, C3bc and the terminal C5b-9 complex TCC) were drawn before start of surgery (T0) and at the following time-points after start of surgery: 180 min (T1), 360 min (T2), 24 h (T3) and 3-5 days (T4). A significant increase in the alternative pathway activation product Bb and in the terminal pathway activation product TCC was seen over time in both groups (P < 0.001). Bb peaked early (T1) and returned to baseline levels post-operatively, whereas TCC increased steadily with maximum values in the late post-operative period. The plasma concentrations of C4d and C3bc decreased significantly in both groups at T1 and T2 and returned to baseline levels at T4. There was no significant difference between the groups. Rectal surgery causes activation of the complement system. Complement is activated through the alternative pathway. Results mostly showed no significant differences between laparoscopic and open rectal surgery apart from lower levels of factor Bb in the former group in the perioperative period.     

Free amino acids in muscle tissue and plasma during exercise in man

Blood and muscle samples (percutaneous biopsy of m. quadriceps femoris) were taken before exercise and after 10 and 20 min of exercise in four healthy subjects working on a bicycle ergometer with a load of 70% of Vo2 max. Free amino acids were determined in plasma and muscle and the intracellular concentration of each amino acid was calculated by the chloride method. The plasma concentration of alanine, arginine and glutamine increased during exercise. In muscle there was an increase in glutamine and alanine concentration and a decrease in glutamate concentration at 10 min of exercise; after 20 min of exercise the increase in alanine and glutamine concentrations was less marked, but the decrease in glutamate concentration was of a similar magnitude. The results demonstrate that glutamate is a quantitatively important ammonia acceptor during heavy exercise.     

Changes in free amino acid concentration in the hemolymph of the female Culex pipiens pallens (Diptera: Culicidae), after a blood meal

The analysis of the free amino acids in the hemolymph of female Culex pipiens pallens L. indicated that asparagine, glutamine, glycine, leucine, serine, threonine, tyrosine, and valine noticeably increased in concentration during a blood meal digestion at 22 degrees C. The concentrations started to rise at about 4 h, reaching maximal level at 12-24 h, and then gradually returned to the prefeeding level by the fifth day after the blood meal. Before the sharp increase, the concentrations of asparagine, glutamine, glycine, serine, threonine, and tyrosine declined slightly during the first 1-2 h, probably because of hemolymph dilution by water absorbed from the blood meal. Histidine and lysine also showed a minor decrease soon after blood feeding, followed by a moderate but noticeable increase, delaying maximal concentrations until 48 h after the blood meal. Proline and alanine both exhibited a high hemolymph content and changed greatly, but with a large variation between the two samples analyzed. The changing pattern of individual hemolymph amino acids depended to a large extent upon the content of each amino acid in the blood meal given to the mosquitoes. Other free amino acids detected in the hemolymph were at very small concentrations and except for phenylalanine did not show any changes after a blood meal. The total free amino acid concentration was 50 nmol (or 6 micrograms) per microliters hemolymph before a blood meal, and increased to a maximal concentration of 88 nmol (or 11 micrograms) per microliters hemolymph at 18 h after the blood meal.     

Delayed metabolic changes after strenuous exertion in trained young men

Twenty apparently healthy, young male volunteers, aged 18-25 (mean 19.3, SD 1.4) years received a 6 months standardized, graded outdoor physical training and were screened for serum magnesium concentration (S-Mg), serum calcium concentration (S-Ca), serum aspartate amino transferase (S-AST), serum alanine amino transferase (S-ALT), serum creatine kinase activity (S-CK), other laboratory variables, weight, and VO2 ml.kg-1.min-1 [corrected] (VO2 max), before a 70 km march, as well as at 1, 24 and 72 h and 18 days after. Maximal aerobic power, body weight, haemoglobin, haematocrit, serum creatinine, total protein and albumin remained unchanged throughout. Immediately after the march, S-Mg did not change, S-AST, S-ALT and S-CK rose, but the rise was not statistically significant, while small but significant rises in S-Ca (P less than 0.05, Student's t-test) and serum cholesterol (P less than 0.01) normalized at 24 h. At 72 h after the march, a significant fall in S-Mg was found (P less than 0.01), together with a second significant rise in S-Ca (P less than 0.05). After 18 days, with no intervening marches or dietary changes, S-Mg remained significantly lowered (P less than 0.05), mean S-ALT and S-CK became significantly raised for the first time (P less than 0.001 and P less than 0.01 respectively), whereas S-Ca normalized. Concomitantly, for the first time there was now a significant rise in blood sugar (P less than 0.001), serum triglycerides (P less than 0.01), and a second rise of serum cholesterol (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Caprylic acid infusion acts in the liver to decrease food intake in rats

Hepatic portal vein (HPV) infusion of the medium chain fatty acid caprylic acid (CA; 2.3 mg/min, 40 microl/min) for 90 min beginning at dark onset in 18-h food-deprived male rats reduced the size of the first nocturnal meal about 40% (P < 0.01) and reduced 24-h food intake by about 15% (P < 0.001). Identical infusions into the vena cava affected neither initial meal size nor food intake. HPV CA infusion attenuated the postprandial decreases in plasma free fatty acids (P < 0.01) and beta-hydroxybutyrate (P < 0.01). HPV CA infusions did not significantly reduce nocturnal saccharine intake in a two-bottle conditioned taste aversion test, and there was no association between the saccharine intake on the test day and the feeding-inhibitory effect of CA on the conditioning day. HPV CA infusion did not affect plasma concentrations of corticosterone or of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha. HPV CA infusion did not increase plasma concentration of the liver enzyme alanine aminotransferase, but did increase plasma concentration of gamma-glutamyl transferase, although not into the pathophysiological range. These data indicate that CA acts in the liver to produce a signal that inhibits feeding and that this inhibitory effect may be related to increases in hepatic fatty acid oxidation rather than be the result of aversion or toxicity.     

Experimental allergic neuritis: effect of plasma infusions.

The effect of intravenous fresh frozen plasma (FFP) and artificial plasma infusions upon the clinical course of chronic experimental allergic neuritis (EAN) in the rabbit was investigated. A total of 12 animals allocated to treatment groups received rabbit FFP or a gelatin plasma expander Haemaccel (Hoechst) and were compared to 13 control non-treated animals. Animals receiving Haemaccel at a rate of 15 ml/kg/day for 7 days showed no significant clinical benefit at any stage. However, animals receiving 15 ml/kg/day FFP for 8 days showed significant clinical benefit during treatment initiated at the onset of definite neurological symptoms of EAN (Mann-Whitney U test, day 4 post-allocation P less than 0.05; day 6 post-allocation P less than 0.01; day 8 post-allocation P less than 0.05). Relapse was observed after cessation of treatment such that comparisons of clinical scores at day 14 and 22 post-allocation revealed no significant differences. Analysis of plasma anti-myelin IgG levels by ELISA showed that non-immunogenic plasma volume expansion decreased anti-myelin IgG concentrations immediately by an average of 34% but had no long-term effect. In contrast, anti-myelin IgG concentrations in FFP infused animals were significantly decreased, compared to controls, when measured 24 h after the last infusion (Student's t-test P less than 0.05). Identical percentage weight losses for both control and treatment groups post-allocation indicated that this decrease was immunologically mediated and not due to plasma dilution. Similar plasma cortisol concentrations measured in both groups showed no significant artifactual induction of endogenous steroid production. Infusions of FFP during early disease progression are able to mediate clinical remission in animals with chronic EAN.     

Effect of branched-chain amino acid supplementation on the exercise-induced change in aromatic amino acid concentration in human muscle

A mixture of the three branched-chain amino acids (BCAAs) was supplied to subjects during two types of sustained intense exercise, a 30 km cross-country race and a full marathon, and the effect on plasma and muscle concentrations of aromatic and BCCAs was studied. When BCAAs (7.5–12 g) were taken during exercise, the plasma and muscle (vastus lateralis) concentration of these amino acids increased, while in the placebo groups the concentration of BCAAs decreased in the plasma and remained unchanged in the muscle. In the placebo group, both types of exercise caused a 20–40% increase in the muscle concentration of the aromatic amino acids, tyrosine and phenylalanine, and the plasma concentration of these amino acids was increased after the marathon. Since tyrosine and phenylalanine are neither taken up nor metabolized by skeletal muscle, the increases in their concentrations in muscle might indicate net protein degradation during exercise. However, when the subjects were supplied with BCAAs during exercise, the increases in tyrosine and phenylalanine concentrations in both muscle and plasma were prevented. These results suggest that an intake of BCAAs during exercise can prevent or decrease the net rate of protein degradation caused by heavy exercise.     

Effect of branched-chain amino acid supplementation on the exercise-induced change in aromatic amino acid concentration in human muscle.

A mixture of the three branched-chain amino acids (BCAAs) was supplied to subjects during two types of sustained intense exercise, a 30 km cross-country race and a full marathon, and the effect on plasma and muscle concentrations of aromatic and BCAAs was studied. When BCAAs (7.5-12 g) were taken during exercise, the plasma and muscle (vastus lateralis) concentration of these amino acids increased, while in the placebo groups the concentration of BCAAs decreased in the plasma and remained unchanged in the muscle. In the placebo group, both types of exercise caused a 20-40% increase in the muscle concentration of the aromatic amino acids, tyrosine and phenylalanine, and the plasma concentration of these amino acids was increased after the marathon. Since tyrosine and phenylalanine are neither taken up nor metabolized by skeletal muscle, the increases in their concentrations in muscle might indicate net protein degradation during exercise. However, when the subjects were supplied with BCAAs during exercise, the increases in tyrosine and phenylalanine concentrations in both muscle and plasma were prevented. These results suggest that an intake of BCAAs during exercise can prevent or decrease the net rate of protein degradation caused by heavy exercise.     

Alterations in amino acid concentrations in the plasma and muscle in human subjects during 24 h of simulated adventure racing

This investigation was designed to evaluate changes in plasma and muscle levels of free amino acids during an ultra-endurance exercise and following recovery. Nine male ultra-endurance trained athletes participated in a 24-h standardized endurance trial with controlled energy intake. The participants performed 12 sessions of running, kayaking and cycling (4 × each discipline). Blood samples were collected before, during and after exercise, as well as after 28 h of recovery. Muscle biopsies were taken before the test and after exercise, as well as after 28 h of recovery. During the 24-h exercise, plasma levels of branched-chain (BCAA), essential amino acids (EAA) and glutamine fell 13, 14 and 19% (P < 0.05), respectively, whereas their concentrations in muscle were unaltered. Simultaneously, tyrosine and phenylalanine levels rose 38 and 50% (P < 0.05) in the plasma and 66 and 46% (P < 0.05) in muscle, respectively. After the 24-h exercise, plasma levels of BCAA were positively correlated with muscle levels of glycogen (r ² = 0.73, P < 0.05), as was the combined concentrations of muscle tyrosine and phenylalanine with plasma creatine kinase (R ² = 0.55, P < 0.05). Following 28-h of recovery, plasma and muscle levels of amino acids had either returned to their initial levels or were elevated. In conclusion, ultra-endurance exercise caused significant changes elevations in plasma and muscle levels of tyrosine and phenylalanine, which suggest an increase in net muscle protein breakdown during exercise. There was a reduction in plasma concentrations of EAA and glutamine during exercise, whereas no changes were detected in their muscle concentration after exercise.     

Transcapillary extravasation rate of albumin in rat skeletal muscle. Effect of motor activity

Transcapillary extravasation of albumin in hindlimb and neck skeletal muscle of rats was determined as extravascular plasma equivalent volumes (I-HSAev), 1-168 h after a single intravenous injection of radiolabelled human serum albumin (I-HSA). One experimental group was immobilized in pentobarbital anaesthesia for the first 8 h after injection of I-HSA. With longer extravasation periods, the rats then woke up and moved freely. In the other experimental group, injections were made in ether anaesthesia allowing the rats to move freely within 10 min after injection. One hour after injection, I-HSAev in the immobilized group averaged 1.5 10(-3) ml g-1 in neck and hindlimb muscle. In the mobile group, I-HSAev was two to three times higher than in the immobilized rats up to 12 h in both muscle groups (P less than 0.05). At 24 h and later I-HSAev was similar in mobile and immobile rats (P greater than 0.05). The I-HSAev increased up to 48 h, levelling off at about 0.06 and 0.08 ml g-1 in hindlimb and neck skeletal muscle, respectively. Corresponding interstitial albumin concentration, calculated from steady-state I-HSAev and interstitial fluid volume (51Cr-EDTA space), averaged 48% and 34% of plasma albumin concentration, respectively.     

Measurement of blood-brain barrier permeability of rats with alpha-aminoisobutyric acid during microdialysis: possible application to behavioral studies.

The purpose of this study was to determine the suitability of alpha-aminoisobutyric acid (AIB) as a marker of the integrity of the blood-brain barrier (BBB) during studies in which amino acid content in dialysates collected by microdialysis probes and behavior of the rat are studied concurrently. AIB (200 mg/kg) was injected intraperitoneally at 1800 h into 24-h fasted, ketamine-acepromazine anesthetized rats on either 10 or 30 days following guide cannula implantation. Dialysates from the medial preoptic area and blood from the tail vein were collected 1 h before and after the AIB injection. Analysis of amino acids, including AIB, in the collections was conducted by reverse-phase HPLC. In 21 of 24 rats, AIB in dialysates averaged less than 3% of plasma at 10, 30, and 50 min after AIB injection. In those rats unidirectional blood-to-brain transfer constant, K(i), of AIB was constant and a good relationship was found between dialysate amino acid concentrations and those predicted from calculations of transport based on the brain uptake index (BUI) for some amino acids. AIB concentration in dialysates was greater than 10% of plasma at 30 min in only 3 of 24 rats. We conclude that AIB can be used as a marker to monitor the integrity of the BBB during serial measurements of dialysate concentrations of amino acids and has application in behavioral studies.     

术后自控镇痛对下腹部手术患者Th细胞亚群的影响

目的：探讨术后自控镇痛对手术患者Th细胞免疫功能的影响。方法：将50例下腹部手术患者随机分为自控硬膜外镇痛（PCEA）组和对照组,术后PCEA组予以PCEA,对照组不施行PCEA,观察两组镇痛效果和T辅助细胞（Th细胞）亚群的变化。结果：PCEA组患者取得满意的镇痛效果,术后VAS评分明显低于对照组（P〈0.05）。麻醉前、术后第1d两组Thl/Th2比值基本一致（P〉0.05）;术后第3d、术后第5d和术后第7dPCEA组Thl/Th2比值明显高于对照组（P〈0.05）。结论：术后良好的自控镇痛对Th细胞功能有一定的保护作用,有利于Th细胞功能维持在Th1型优势反应状态。     

Daily patterns of plasma atrial natriuretic peptide, serum osmolality and haematocrit in the rat.

The present study documents daily rhythms of plasma atrial natriuretic peptide, serum osmolality and haematocrit in the rat. One-hundred and twenty-five Sprague-Dawley rats were used. They were bred under a cycle of 12 h light/12 h dark starting at 07.00 h. Fifty-three rats were decapitated between 09.00 and 16.00 h (study I) and 72 rats in groups of six were decapitated at 2-h intervals for a period of 24 h (study II). In study I, plasma atrial natriuretic peptide was 156 +/- 11 pg mg-1 (mean +/- SEM). In study II, atrial natriuretic peptide was at a control level from 08.00 to 18.00 h and then began to increase. At 22.00 h, atrial natriuretic peptide was 420 +/- 105 pg ml-1, which was significantly higher than at 08.00 h (P less than 0.05). The serum osmolality was over 300 mosmol kg-1 during the day. The highest mean osmolalities (315, 317, 312 mosmol kg-1) were found from 18.00 to 22.00 h. These were significantly different (P less than 0.05) from other groups during the day. The haematocrit was highest at 14.00 h (49.5 +/- 0.7%) and lowest at 24.00 h (43.6 +/- 0.8%) (P less than 0.05). In conclusion, we have shown that there are significant daily rhythms of plasma atrial natriuretic peptide, serum osmolality and haematocrit during a 24-h period and 12 h light/12 h dark cycle in the rat.     

Biochemical changes in a 100 km run: Free amino acids,urea, and creatinine

Summary Free amino acids, urea, and creatinine were analyzed in venous blood and urine of 11 trained (28–81 years old) male subjects before, immediately after, and 1 day after a 100 km running competition.The urinary excretion per minute of all amino acids was lowered after the contest. The renal clearance of creatinine was reduced from 116 to 60 ml/min and the clearance of most amino acids was reduced to a similar extent. However, for the amino acids with a resting clearance under 1 ml/min (x), a high relative clearance ratio (y in % of x) was seen post-exercise: y = -92.3 (log₁₀ x) +23.1, r= -0.83, showing that their high reabsorption capacity had been impaired.Serum concentrations of most free amino acids, including the branched-chain amino acids and alanine, were reduced to 35–85% of the pre-race values. The sulfur amino acids were elevated either at the end of (cystine, to 180%) or 24 h after (methionine, to 155%) the race. Urea production increased by 44% while creatinine production tended to decrease. The production of 3-methylhistidine remained unchanged. These findings are compatible with a stimulation of gluconeogenesis at the expense of the amino acid pool without induction of muscle protein catabolism.The results presented in this paper are part of a collaborative study with Dr. J. Keul's group in Freiburg i. B./Federal Republic of Germany, Dr. H. Howald's group in Macolin/Switzerland, and Dr. J. R. Poortmans' laboratory in Brussels/Belgium     

Some aspects of the acute phase response after a marathon race,and the effects of glutamine supplementation

Strenuous exercise may be associated with immune suppression. However, the underlying mechanism is not known. A decrease in the plasma level of glutamine, which is utilised at a high rate by cells of the immune system, and an increase in the plasma level of some cytokines may impair immune functions such as lymphocyte proliferation after prolonged, exhaustive exercise. In two separate studies of the Brussels marathon, using similar protocols, the time course of the changes in the plasma concentrations of some amino acids (glutamine, glutamate, alanine, tryptophan and branched chain amino acids), acute phase proteins and cytokines (interleukins IL-1α, IL-2, IL-6, tumour necrosis factor type a) was measured in male athletes. The numbers of circulating leucocytes and lymphocytes were also measured. Amino acid and cytokine concentrations have not previously been measured concomitantly in marathon runners; the measurement of some of these parameters the morning after the marathon (16?h) is novel. Another novel feature is the provision of glutamine versus placebo to marathon runners participating in the second study. In both studies the plasma concentrations of glutamine, alanine and branched chain amino acids were decreased immediately after and 1?h after the marathon. Plasma concentrations of all amino acids returned to pre-exercise levels by 16?h after exercise. The plasma concentration of the complement anaphylotoxin C5a increased to abnormal levels after the marathon, presumably due to tissue damage activating the complement system. There was also an increase in plasma C-reactive protein 16?h after the marathon. The plasma levels of IL-1α were unaffected by the exercise, while that of IL-2 was increased 16?h after exercise. Plasma IL-6 was increased markedly (≈ 45-fold) immediately after and at 1?h after exercise. Neopterine, a macrophage activation marker, was significantly increased post-exercise. There was a marked leucocytosis immediately after the marathon, which returned to normal 16 h later. At the same time there was a decrease in the number of T-lymphocytes, which was further reduced within 1 h to below pre-exercise levels. Glutamine supplementation, as administered in the second study, did not appear to have an effect upon lymphocyte distribution.