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Biomedical subjects

L M Castell

Publications and source records attributed to L M Castell.

17 recordsLinked to original sources
PubMed2001

The relation between glutamine and the immunodepression observed in exercise.

Glutamine is the most abundant amino acid in the body. It is an important fuel for some key cells of the immune system. Both the plasma concentration of glutamine and the functional ability of immune cells in the blood are decreased after prolonged, exhaustive exercise. Glutamine feeding has had beneficial effects in clinical situations, and the provision of glutamine after intensive exercise has decreased the incidence of infections, particularly of upper respiratory tract infections. However, the precise effect of glutamine on immunodepression in this situation is not yet established.

Amino Acids↗
PubMed2001

Physical exercise and normobaric hypoxia: independent modulators of peripheral cholecystokinin metabolism in man.

The purpose of the present investigation was to determine the independent effects of hypoxia and physical exercise on peripheral cholecystokinin (CCK) metabolism in humans. Thirty-two physically active men were randomly assigned in a double-blind manner to either a normoxic (N; n = 14) or hypoxic (H; n = 18) group. During the acute study, subjects in the H group only participated in two tests, separated by 48 h, which involved a cycling test to exhaustion in normobaric normoxia and normobaric hypoxia (inspired O(2) fraction = 0.21 and 0.16, respectively). In the intermittent study, N and H groups cycle-trained for 4 wk at the same relative exercise intensity in both normoxia and hypoxia. Acute normoxic exercise consistently raised plasma CCK during both studies by 290-723%, which correlated with increases in the plasma ratio of free tryptophan to branched chain amino acids (r = 0.58-0.71, P < 0.05). In contrast, acute hypoxic exercise decreased CCK by 7.0 +/- 5.5 pmol/l, which correlated with the decrease in arterial oxygen saturation (r = 0.56, P < 0.05). In the intermittent study, plasma CCK response at rest and after normoxic exercise was not altered after physical training, despite a slight decrease in adiposity. We conclude that peripheral CCK metabolism 1) is more sensitive to acute changes than chronic changes in energy expenditure and 2) is potentially associated with acute changes in tissue PO(2) and metabolic precursors of cerebral serotoninergic activity.

Adult↗
PubMed1999

The role of tryptophan in fatigue in different conditions of stress.

Tryptophan is the precursor for the neurotransmitter 5-hydroxytryptamine (5-HT), which is involved in fatigue and sleep. It is present in bound and free from in the blood, where the concentration is controlled by albumin binding to tryptophan. An increase in plasma free tryptophan leads to an increased rate of entry of tryptophan into the brain. This should lead to a higher level of 5-HT which may cause central fatigue. Central fatigue is implicated in clinical conditions such as chronic fatigue syndrome and post-operative fatigue. Increased plasma free tryptophan leads to an increase in the plasma concentration ratio of free tryptophan to the branched chain amino acids (BCAA) which compete with tryptophan for entry into the brain across the blood-brain barrier. The plasma concentrations of these amino acids were measured in chronic fatigue syndrome patients (CFS) before and after exercise (Castell et al., 1998), and in patients undergoing major surgery (Yamamoto et al., 1997). In the CFS patients, the pre-exercise concentration of plasma free tryptophan was higher than in controls (p < 0.05) but did not change during or after exercise. This might indicate an abnormally high level of brain 5-HT in CFS patients leading to persistent fatigue. In the control group, plasma free tryptophan was increased after maximal exercise (p < 0.001), returning towards baseline levels 60 min later. The apparent failure of the CFS patients to change the plasma free tryptophan concentration or the free tryptophan/BCAA ratio during exercise may indicate increased sensitivity of brain 5-HT receptors, as has been demonstrated in other studies (Cleare et al., 1995). In post-operative recovery after major surgery plasma free tryptophan concentrations were markedly increased compared with baseline levels; the plasma free tryptophan/BCAA concentration ratio was also increased after surgery. Plasma albumin concentrations were decreased after surgery: this may account for the increase in plasma free tryptophan levels. Provision of BCAA has improved mental performance in athletes after endurance exercise (Blomstrand et al., 1995, 1997). It is suggested that BCAA supplementation may help to counteract the effects of an increase in plasma free tryptophan, and may thus improve the status of patients during or after some clinically stressful conditions.

Amino Acids↗
PubMed1999

Effects of exercise intensity, duration and recovery on in vitro neutrophil function in male athletes.

The aim of the present study was to compare the effects of exercise at 80% VO2max (resulting in fatigue within 1 h) with more prolonged exercise at a lower work rate (55% VO2max for up to 3 h) on blood neutrophil function and plasma concentrations of cortisol, glutamine and glucose. Eighteen healthy male subjects (mean+/-SD age 22.5+/-3.7 yrs, VO2max 60.1+/-6.6 ml x kg(-1) x min(-1)) cycled on an electrically braked ergometer at 80% VO2max to fatigue (37+/-19 min). On another occasion, separated by at least one week, subjects performed exercise on the same ergometer at 55% VO2max for 3 h or to fatigue, whichever was the sooner. Mean exercise time was 164+/-23 min. The order of the trials was randomised. Both exercise bouts caused significant (p<0.05) elevations of the blood leucocyte count and plasma cortisol concentration and reductions in the in vitro neutrophil degranulation response to bacterial lipopolysaccharide and oxidative burst activity. After exercise at the lower work rate for a longer duration, plasma cortisol concentration was higher, blood leucocyte and neutrophil counts were higher, blood lymphocytes, plasma glucose and indices of neutrophil function were lower than those observed at 80% VO2max. Plasma glutamine only fell significantly during recovery after the more prolonged exercise. We conclude that when exercise is very prolonged, the diminution of innate immune function is greater, or at least as great as that observed after fatiguing exercise at higher work rates. Furthermore, reductions in neutrophil function after exercise at 80% VO2max were not related to changes in the plasma glutamine concentration, although both plasma glutamine and neutrophil function were decreased at 1 and 2.5 h post-exercise in the long duration exercise trial.

Adult↗
PubMed1999

Food for thought.

Explore the source record for details and available documents.

Amino Acids, Branched-Chain↗
PubMed1998

Glutamine and the effects of exhaustive exercise upon the immune response.

There is a high incidence of infections in athletes undergoing intense, prolonged training or participating in endurance races (e.g., the marathon), in particular, upper respiratory tract infections. Prolonged, exhaustive exercise can lower the plasma level of the amino acid, glutamine, which is an important fuel for some cells of the immune system and may have specific immunostimulatory effects. This could therefore be an important factor in the event of an impaired response of immune cells to opportunistic infections. The effects of feeding glutamine to sedentary individuals and to marathon and ultramarathon runners before and after prolonged, exhaustive exercise has been investigated in a series of studies that monitored the incidence of infections and some acute-phase response markers. Oral glutamine, compared with a placebo, appeared to have a beneficial effect on the incidence of infections reported by runners after a marathon.

Animals↗
PubMed1997

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-1 alpha, 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-1 alpha were unaffected by the exercise, while that of IL-2 was increased 16 h after exercise. Plasma IL-6 was increased markedly (approximately 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.

Acute-Phase Proteins↗
PubMed1997

Responses of plasma glutamine, free tryptophan and branched-chain amino acids to prolonged exercise after a regime designed to reduce muscle glycogen.

Prolonged exercise can elicit a reduction in the plasma glutamine concentration and an increase in the plasma concentration ratio of free tryptophan (FTrp) to branched-chain amino acids (BCAA). The purpose of this investigation was to study the effects of a 60-min bout of vigorous treadmill running with dietary manipulation on plasma concentrations of glutamine, FTrp and BCAA after an exercise and diet regime designed to reduce muscle glycogen. Seven male distance runners [mean (SD) age: 29.3 (2.1) years; VO2max: 62.7 (3.3) ml.kg-1.min-1] acted as subjects. Each undertook a regime designed to reduce muscle glycogen, then performed a 60-min treadmill run (75% VO2max) under two dietary conditions: after a 14-h fast (fasted) and after ingestion of a high carbohydrate meal (30 kJ.kg-1: 80% carbohydrate, 10% protein, 10% fat) 3 h before running (fed). Plasma concentrations of glutamine, FTrp, BCAA, free fatty acids (FFA), glycerol and glucose were measured 5 min before and 5 min after the run, under each dietary condition. Plasma glutamine did not change in response to exercise when fasted (P > 0.05), but increased when fed (P = 0.007). Plasma FTrp increased under both dietary conditions (P < 0.001), but the magnitude of this increase was greater when fasted than when fed (P < 0.001). Plasma BCAA did not change under either dietary condition (P < 0.05). Increases in the plasma FTrp/BCAA ratio reflected increases in plasma FFA and glycerol concentrations (P < 0.001; both dietary conditions) and these changes were all greater under fasted conditions when a fall in blood glucose concentration was observed (P = 0.007). These data emphasise the importance of dietary carbohydrate intake between repeated bouts of prolonged exercise on responses of plasma glutamine, FTrp and BCAA during subsequent exercise.

Adult↗
PubMed1997

Changes in the albumin binding of tryptophan during postoperative recovery: a possible link with central fatigue?

Tryptophan is the precursor of the neurotransmitter 5-hydroxytryptamine (5-HT), known to be involved in sleep and fatigue. In the blood, tryptophan binds to albumin, and that which does not, free tryptophan, competes with branched chain amino acids (BCAA) for entry into the brain. The plasma concentrations of albumin, free tryptophan, total tryptophan, and BCAA were measured before and after major surgery in nine elderly and nine coronary artery bypass graft (CABG) patients. In both the elderly and the CABG patients plasma free tryptophan concentrations were increased after surgery, compared with baseline levels; the plasma free tryptophan/BCAA concentration ratio was also increased significantly after surgery. Plasma albumin concentrations were decreased significantly after surgery in both the elderly and the CABG patients. Plasma BCAA concentrations were not affected by surgery in either group. The effect of exercising to exhaustion on 5-HT and tryptophan were investigated in Nagase analbuminemic rats (NAR). The intrasynaptosomal concentration of tryptophan, 5-hydroxy-tryptophan, and 5-HT was increased by fatigue after exercise. In addition, running time to exhaustion was shortened in NAR. These data suggest that free tryptophan uptake and 5-HT synthesis were enhanced in the nerve terminal. A decrease in plasma albumin may account for the increase in plasma-free tryptophan levels. An increase in plasma free tryptophan, resulting in an enhanced plasma concentration ratio of free tryptophan/BCAA, may lead to a higher 5-HT concentration in some parts of the brain and, consequently, to central fatigue. It is suggested that provision of BCAA as a dietary supplement may counteract the increase in plasma free tryptophan and thus improve the status of some patients after major surgery.

Aged↗
PubMed1996

Does glutamine have a role in reducing infections in athletes?

There is an increased risk of infections in athletes undertaking prolonged, strenuous exercise. There is also some evidence that cells of the immune system are less able to mount a defence against infections after such exercise. The level of plasma glutamine, an important fuel for cells of the immune system, is decreased in athletes after endurance exercise; this may be partly responsible for the apparent immunosuppression which occurs in these individuals. We monitored levels of infection in more than 200 runners and towers. The levels of infection were lowest in middle-distance runners, and highest in runners after a full or ultramarathon and in elite rowers after intensive training. In the present study, athletes participating in different types of exercise consumed two drinks, containing either glutamine (Group G) or placebo (Group P) immediately after and 2 h after exercise. They subsequently completed questionnaires (n = 151) about the incidence of infections during the 7 days following the exercise. The percentage of athletes reporting no infections was considerably higher in Group G (81%, n = 72) than in Group P (49%, n = 79, p < 0.001).

Adult↗
PubMed1994

Growth hormone suppression and glutamine flux associated with cardiac surgery.

Pharmacological doses of growth hormone (GH) in humans and rats increase plasma and muscle glutamine values. As major surgery results in a physiological rise in serum GH concentration, we investigated whether this physiological increase in GH altered glutamine metabolism. Eighteen patients undergoing coronary artery bypass graft (CABG) surgery were randomly assigned to receive somatostatin, 100 micrograms subcutaneously at induction of anaesthesia and 8 hourly for 48 h, or placebo. Somatostatin effectively blocked the physiological surge of GH following injury but did not affect plasma or muscle glutamine concentrations, which fell significantly in both groups. Plasma glutamine decreased by 31% (P < 0.01) and 28% (P < 0.01) in the control and somatostatin groups respectively. Muscle glutamine was reduced 45% (P < 0.001) in the control group and 50% (P < 0.001) in the somatostatin group. There was no difference in muscle or circulating glutamate, alanine or branched chain amino acid concentrations or in metabolite values between the somatostatin-treated patients and the control group. There was no relationship between the GH response to surgery and glutamine metabolism following major surgery.

Blood Glucose↗
PubMed1992

Separation of peripheral blood lymphocytes with low platelet and erythrocyte contamination, using ADP aggregation.

A simple and inexpensive method to obtain substantially platelet-free and erythrocyte-free lymphocyte preparations from human peripheral blood has been established, using a modification of the technique published by Vives et al. (1971). Lymphocyte levels of up to 3 x 10(6) per ml blood have been obtained, with 2-3% platelet and erythrocyte contamination per ml blood, by pre-aggregating platelets with low concentrations of adenosine 5'diphosphate (ADP).

Blood Platelets↗
PubMed1989

Correlation of blood pressure in normotensive and hypertensive individuals with platelet but not lymphocyte intracellular free calcium concentrations.

1. Fifty-two normotensive and essential hypertensive subjects were studied. Intracellular free calcium concentration [( Ca2+]i) was measured in lymphocytes (37 subjects) and platelets (18 subjects) by means of the fluorescent indicators, quin 2 and fura-2. In 31 subjects, plasma ionized calcium concentration was also measured. 2. There was a positive correlation between platelet [Ca2+]i and systolic blood pressure (r = 0.485, P less than 0.05), diastolic blood pressure (r = 0.542, P less than 0.02) and mean blood pressure (r = 0.534, P less than 0.02). 3. No statistically significant relationship was observed between plasma ionized calcium and blood pressure. 4. No relationship was found between lymphocyte [Ca2+]i and blood pressure, or between lymphocyte [Ca2+]i and plasma ionized calcium. 5. There was no relationship between [Ca2+]i of lymphocytes and platelets measured simultaneously from the same subject. 6. These findings reconcile previous conflicting reports and show a relationship between platelet but not lymphocyte [Ca2+]i and blood pressure in man.

Adult↗
PubMed1985

Measurement of free Ca2+ changes and total Ca2+ release in a single striated muscle fibre using the fluorescent indicator quin 2.

The fluorescent Ca2+ indicator, quin 2, has been used in isolated striated muscle fibres. There is a distinct quin 2 fluorescence peak at lambda 500 nm upon excitation at lambda 339 nm after axial injection of the potassium salt of quin 2, pH 7.1. Single voltage-clamp or current clamp electrical stimulation resulted in a distinct transient change in the fluorescence at lambda 500 nm which was not observed at lambda 400 nm, the peak of the fibre autofluorescence. Ca2+ buffering is marked at high quin 2 concentrations (greater than or equal to 400 microM) producing a slow decay of force and fluorescence. At lower concentrations (8-30 microM) of quin, the decay of force is within the range observed in non-injected control fibres. A Kd of 457 nM at 5 mM free Mg2+ suggests an upper resting free Ca2+ concentration of 310 nM at 12 degrees C.

Aminoquinolines↗
PubMedDate not supplied

The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise.

Athletes undergoing intense, prolonged training or participating in endurance races suffer an increased risk of infection due to apparent immunosuppression. Glutamine is an important fuel for some cells of the immune system and may have specific immunostimulatory effects. The plasma glutamine concentration is lower after prolonged, exhaustive exercise: this may contribute to impairment of the immune system at a time when the athlete may be exposed to opportunistic infections. The effects of feeding glutamine was investigated both at rest in sedentary controls and after exhaustive exercise in middle-distance, marathon and ultra-marathon runners, and elite rowers, in training and competition. Questionnaires established the incidence of infection for 7 d after exercise: infection levels were highest in marathon and ultra-marathon runners, and in elite male rowers after intensive training. Plasma glutamine levels were decreased by approximately 20% 1 h after marathon running. A marked increase in numbers of white blood cells occurred immediately after exhaustive exercise, followed by a decrease in the numbers of lymphocytes. The provision of oral glutamine after exercise appeared to have a beneficial effect on the level of subsequent infections. In addition, the ratio of T-helper/T-suppressor cells appeared to be increased in samples from those who received glutamine, compared with placebo.

Administration, Oral↗
PubMedDate not supplied

Changes in blood markers of serotoninergic activity following high intensity cycle ergometer exercise.

The purpose of this study was to measure concentrations of adrenaline (A), noradrenaline (NE), free tryptophan (f-Trp), prolactin (PRL), nonesterified fatty acids (NEFA), and blood lactate following 30 s of high-intensity cycle ergometer exercise. Adrenaline (A) and NE concentrations increased immediately postexercise (P < 0.05) and returned to levels observed at baseline 24 h later. Plasma f-Trp concentration decreased by 23.5% immediately following exercise (P < 0.05). There were no changes observed in serum concentrations of PRL. Plasma NEFA concentrations decreased immediately following exercise by 46% (P < 0.05) and returned to baseline values 24 h later. Whole blood lactate concentrations increased immediately post exercise (P < 0.05), and were higher than those measured 24 h later (P < 0.05). These findings indicate that blood markers of serotoninergic activity were unaltered by a single 30 s bout of maximal cycling.

Adult↗