[Evaluation of glomerular filtration rate in clinical practice]. / La mesure du débit de filtration glomérulaire en clinique quotidienne.

Glomerular filtration rate (GFR) is the most frequently used parameter to evaluate the renal function. GFR may be estimated with serum creatinine, creatinine clearance based on 24 hours urine collection or Cockcroft formula. All these methods have bias. Other approaches have thus been proposed. The limitations and advantages of isotopic methods and recent mathematical approaches (MDRD formula) are reviewed.

[Analysis of results taken with "tweezers": some pitfalls in clinical biological interpretation]. / Des résultats d'analyses à prendre avec des "pincettes": quelques pièges de l'interprétation en biologie clinique.

Like other medical investigations, laboratory tests are not free from uncertainties or errors which limit their clinical value. Usually two levels of variations are identified: the analytical and biological levels. This paper presents some sources of variations and provides different examples. The concept of reference value is also discussed, as well as the clinician's viewpoint regarding the interpretation of laboratory results.

Effects of training on exercise-induced muscle damage and interleukin 6 production.

To address the question of whether the increased plasma concentration of interleukin 6 (IL-6) following strenuous muscular work could be related to exercise-induced muscle damage, 5 moderately active male volunteers underwent two isokinetic exercise sessions in the eccentric mode, separated by a period of 3 weeks during which the subjects underwent five training sessions. Before training, exercise was followed by severe muscle pain (delayed-onset muscle soreness; DOMS), and by significant increases in plasma IL-6 level and serum myoglobin concentration (SMb) (P < 0.001). After training, postexercise DOMS and SMb values were significantly lower than those measured before training. There was no significant difference between plasma IL-6 levels measured at the same time points before and after training. We conclude that the hypothetical relationship between exercise-induced muscle damage and increased postexercise levels of circulating IL-6 is not substantiated by the present results.

Endotoxaemia, production of tumour necrosis factor alpha and polymorphonuclear neutrophil activation following strenuous exercise in humans.

To examine whether endotoxaemia accompanying long-term, strenuous physical exercise is involved in exercise-induced increase in plasma tumour necrosis factor alpha (TNF-alpha) concentration and polymorphonuclear neutrophil (PMN) activation, 14 male recreational athletes [mean age 28 (SEM 1) years] were studied. Exercise consisted of a 1.5-km river swim, a 40-km bicycle race, and a 10-km road race. Mean time to complete the race was 149.8 (SEM 4.8) min. The plasma concentrations of granulocyte myeloperoxidase (MPO) and TNF-alpha were significantly higher than baseline values immediately and 1 h after exercise (P<0.001). Both variables returned to pre-race levels the day after exercise. Marked, transient decreases in plasma concentrations of anti-lipopolysaccharide (LPS) immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies directed against a panel of selected smooth gram-negative LPS were observed after the race, reaching in most cases minimal values in the blood sample drawn immediately following the completion of the triathlon. There was no significant correlation between the magnitude of PMN activation, as assessed by the increase in plasma concentrations of MPO, and the humoral markers of endotoxaemia and TNF-alpha. An inverse, highly significant relationship between the increase in plasma TNF-alpha concentrations and the changes in circulating anti-LPS IgM antibodies concentrations was observed (r = -0.7; P<0.01). These findings suggest that exercise-induced endotoxaemia was involved in the release of TNF-alpha, that the magnitude of the TNF-alpha response to exercise was down-regulated by anti-LPS antibodies of the IgM class, and that the production of TNF-alpha and endotoxaemia did not seem to play a role in the activation of circulating PMN in the exercising subjects.

Possible in vivo tolerance of human polymorphonuclear neutrophil to low-grade exercise-induced endotoxaemia.

To address the question of whether translocation of bacterial lipopolysaccharide (LPS) into the blood could be involved in the process of exercise-induced polymorphonuclear neutrophil (PMN) activation, 12 healthy male subjects who took part in a sprint triathlon (1.5 km river swim, 40 km bicycle race, 10 km road race) were studied. While there was no detectable amount of endotoxin in the blood samples drawn at rest, exercise was followed by the appearance of circulating endotoxin molecules at the end of competition in four subjects, and after one and 24 h recovery in three and seven athletes, respectively. The concentrations of plasma granulocyte myeloperoxidase ([MPO]), were significantly higher immediately after exercise and one hour later-than baseline values (P<0.001). This variable returned to pre-race levels the day after exercise, despite the presence of detectable amounts of LPS, at that time, in seven athletes. The absence of significant correlation (r=0.26; P=0.383) and temporal association between [MPO] and plasma endotoxin levels led us to conclude that endotoxaemia was not involved in the process of exercise-induced PMN degranulation observed in our subjects.

Myocellular enzyme leakage, polymorphonuclear neutrophil activation and delayed onset muscle soreness induced by isokinetic eccentric exercise.

To address the question of whether delayed onset muscular soreness (DOMS) following intense eccentric muscle contraction could be due to increased production of the arachidonic acid derived product prostaglandin E2 (PGE2). 10 healthy male subjects were submitted to eccentric and concentric isokinetic exercises on a Kin Trex device at 60 degrees/s angular velocity. Exercise consisted of 8 stages of 5 maximal contractions of the knee extensor and flexor muscle groups of both legs separated by 1 min rest phases. There was an interval of at least 30 days between eccentric and concentric testing, and the order of the two exercise sessions was randomly assigned. The subjective presence and intensity of DOMS was evaluated using a visual analogue scale, immediately, following 24 h and 48 h after each test. Five blood samples were drawn from an antecubital vein: at rest before exercise, immediately after, after 30 min recovery, 24 h and 48 h after the tests. The magnitude of the acute inflammatory response to exercise was assessed by measuring plasma levels of polymorphonuclear elastase ([EL]), myeloperoxidase ([MPO]) and PGE2 ([PGE2]). Using two way analysis of variance, it appeared that only eccentric exercise significantly increased [EL] and DOMS, especially of the hamstring muscles. Furthermore, a significant decrease in eccentric peak torque of this muscle group only was observed on day 2 after eccentric work (- 21%; P < 0.002). Serum activity of creatine kinase and serum concentration of myoglobin increased significantly 24 and 48 h after both exercise tests. However, these variables reached significantly higher values following eccentric contractions 48 h after exercise. Mean [PGE2] in the two exercise modes remained unchanged over time and were practically equal at each time point. On the basis of these findings, we conclude that the magnitude of polymorphonuclear (PMN) activation, muscle damage, and DOMS are greater after eccentric than after concentric muscle contractions. However, the hypothesized interplay between muscle damage, increased PGE2 production, DOMS sensations, and reduced isokinetic muscle performance was not substantiated by the present results.

Piroxicam fails to reduce myocellular enzyme leakage and delayed onset muscle soreness induced by isokinetic eccentric exercise.

To test the hypothesis that delayed onset muscular soreness (DOMS) following intense eccentric muscle contraction could be due to increased production of prostaglandin E(2) (PGE(2)), ten healthy male subjects were studied. Using a double-blind randomized crossover design, each subject performed two isokinetic tests separated by a period of at least 6 weeks: once with placebo, and once with piroxicam (Feldene((R))). They were given one capsule containing either placebo or piroxicam (20 mg) per day for 6 days with initial doses given starting 3 days prior to isokinetic testing. Exercise consisted of eight stages of five maximal contractions of the knee extensor and flexor muscle groups of both legs separated by 1 min rest phases, on a Kin Trex device at 60( degrees )/s angular velocity. The subjective presence and intensity of DOMS were evaluated using a visual analogue scale immediately after, and 24 and 48 h after each test. The mean plasma concentration of PGE(2) measured at rest and after exercise was significantly lower in the group treated with piroxicam (p < 0.05). However, statistical analysis (two-way ANOVA test) revealed that exercise did not cause any significant change of mean plasma PGE(2) over time in either of the two groups. Eccentric work was followed by severe muscle pain in extensor and flexor muscle groups. Maximal soreness was noted 48 h postexercise. Serum creatine kinase activity and the serum concentration of myoglobin increased significantly, and reached peak values 48 h after exercise in both experimental conditions (p < 0.001). By paired t-test, it appeared that there were no significant differences in the serum levels of these two markers of muscle damage between the two groups at any time point. We conclude that: (1) oral administration of piroxicam fails to reduce muscle damage and DOMS caused by strenuous eccentric exercise; and (2) the hypothetical role of increased PGE(2) production in eccentric exercise-induced muscle damage, DOMS, and reduced isokinetic performance is not substantiated by the present results.

Blood levels of reduced/oxidized glutathione and plasma concentration of ascorbic acid during eccentric and concentric exercises of similar energy cost.

In an attempt to assess the possible oxidative stress associated with the transient exercise-induced activation of polymorphonuclear neutrophils (PMN), we compared the effects of eccentric and concentric exercises (downhill run: DR and uphill walk: UW, respectively) of equal duration (35 min) and similar energy cost (60% VO2max) on plasma levels of ascorbic acid ([AA]) and blood concentration of reduced ([GSH]) and oxidized ([GSSG]) glutathione. Eight healthy male subjects took part in this study. Plasma concentration of myeloperoxidase ([MPO]) was used as a specific marker of PMN activation. While there were no significant changes in [MPO] and [AA] in UW experiments, [MPO] increased (+80%) and [AA] decreased significantly during DR tests (P < 0.01 and P < 0.05, respectively). A significant negative relationship was observed between [AA] and [MPO] in DR experiments only (r = -0.49; P < 0.01). Mean (+/- SEM) basal GSH and GSSG concentrations, calculated by pooling the values measured before both tests, were 0.54 +/- 0.02 and 0.12 +/- 0.007 mM, respectively. The blood concentration of these compounds remained practically unchanged in both exercise tests. These results confirm the role played by the eccentric component of muscle contraction in transient exercise-induced PMN activation and suggest that this activation was partly involved in the decrease in [AA] observed in DR experiments. The oxidant stress associated with the exercise protocol used in this study was insufficient to alter blood levels of reduced and oxidized glutathione.

Anaphylatoxin C5a production during short-term submaximal dynamic exercise in man.

We studied the effects of short-term submaximal exercise on the plasma levels of myeloperoxidase ([MPO]) and C5a anaphylatoxin ([C5a]), taken as specific markers of polymorphonuclear neutrophil (PMN) and complement activation, respectively. Eleven young, healthy male volunteers were subjected to a constant-load concentric exercise on a cycle ergometer (20 min at 80% maximal oxygen uptake). Mean resting MPO and C5a concentrations were 437 +/- 113 and 0.47 +/- 0.21 ng/ml, respectively. During exercise, [MPO] and [C5a] increased significantly (p < 0.001) towards respective peak values of 649 +/- 131 and 1.3 +/- 0.6 ng/ml. A rapid decrease of both [MPO] and [C5a] was observed during recovery. The similar time course of [MPO] and [C5a] changes and the highly significant relationship between these two variables (r = 0.651; p < 0.001) argues for the possible involvement of the complement anaphylatoxin C5a in the process of PMN degranulation. During exercise, the number of circulating PMN increased (+80%; p < 0.001) and remained practically unchanged up to 20 minutes of recovery. As [MPO] and PMN count were not significantly related (r = 0.2; p < 0.1), we concluded that the activation of PMN was independent of their mobilization.

Effects of methylprednisolone on exercise-induced increases of plasma levels of polymorphonuclear elastase and myeloperoxidase in man. Preliminary results.

The aim of the present study was to verify whether a single oral dose of methylprednisolone could modulate the exercise-induced release of polymorphonuclear neutrophil (PMN) elastase and myeloperoxidase. Four healthy, male subjects were submitted to a 20 min downhill run (-20%) at 60% VO(2) max, 3 h after oral absorption of a placebo or a single dose of 32 mg methylprednisolone. A marked neutrophilia (+103% of basal PMN count; p < 0.02) was observed 3 h after methylprednisolone ingestion. During both exercise trials, placebo and methylprednisolone, PMN counts were increased by 46% and 19% (p < 0.05), respectively. The running test caused marked and significant (p < 0.05) increases in plasma myeloperoxidase concentration (MPO). The magnitude of MPO changes was the same in the two trials (+110%). Exercise also resulted in significant changes in plasma elastase concentration (EL) in both experimental conditions (placebo: +104%, p < 0.05; methylprednisolone: +338%, p < 0.005). Plasma elastase levels reached at the end of exercise on methylprednisolone were significantly higher than after placebo (p < 0.05). A significant relationship was found between EL and PMN in methylprednisolone trial only (r = 0.72; l0 < 0.005). These results showed that the transient exercise-induced release of elastase and myeloperoxidase were not decreased by methylprednisolone.

Inflammatory response to strenuous muscular exercise in man.

Based on the humoral and cellular changes occurring during strenuous muscular work in humans, the concept of inflammatory response to exercise (IRE) is developed. The main indices of IRE consist of signs of an acute phase response, leucocytosis and leucocyte activation, release of inflammatory mediators, tissue damage and cellular infiltrates, production of free radicals, activation of complement, and coagulation and fibrinolytic pathways. Depending on exercise intensity and duration, it seems likely that muscle and/or associated connective tissue damage, contact system activation due to shear stress on endothelium and endotoxaemia could be the triggering mechanisms of IRE. Although this phenomenon can be considered in most cases as a physiological process associated with tissue repair, exaggerated IRE could have physiopathological consequences. On the other hand, the influence of several factors such as age, sex, training, hormonal status, nutrition, anti-inflammatory drugs, and the extent to which IRE could be a potential risk for subjects undergoing intense physical training require further study.

Plasma levels of polymorphonuclear elastase and myeloperoxidase after uphill walking and downhill running at similar energy cost.

This study was designed to compare the effects of eccentric and concentric exercises on blood polymorphonuclear neutrophil count (nPMN) and plasma levels of myeloperoxidase ([MPO]) and elastase ([EL]) used as markers of neutrophil (PMN) activation. Ten healthy male subjects underwent 2 periods of exercise of 20 min duration each at 60% VO2max on an inclined treadmill. They initially walked up a 5% grade (UW). Ten days later they ran downhill on a 20% grade (RD). Blood samples were collected 10 min before and immediately after exercise. A postexercise sample was drawn after 20 min recovery. Both exercise bouts were accompanied by a similar and significant (p < 0.01) increase of 33% in nPMN above resting values. Baseline nPMN values were reached after 20 min recovery. There were no significant changes in [MPO] and [EL] following UW. In contrast, RD was followed by significant increases (p < 0.001) in [MPO] (+97%) and [EL] (+70%) above resting levels. While [MPO] returned to its pre-exercise level after 20 min recovery, [EL] remained significantly elevated (p < 0.05). These results clearly demonstrate the importance of the eccentric component of muscle contraction in exercise-induced PMN activation.

[Mobilization of leukocytes during sub-maximal dynamic exercise]. / Mobilisation des leucocytes lors de l'exercice dynamique sous-maximum.

Increase of blood leucocytes induced by a dynamic exercise has been studied in 10 adult male subjects (age: 22 +/- 2 years; body weight 73 +/- 10 kg; VO2max: 54 +/- 8 ml O2/kg.min. The exercise consisted of a 20 minutes test on a cycle ergometer at a work rate eliciting a total energy expenditure roughly equal to 80% of the maximal aerobic power (80% VO2max). During exercise the absolute number of circulating leucocytes (n Leu) increased significantly toward a maximal value reached in most cases at the end of exercise. The maximal values of n Leu--expressed as percentage of n Leu measured at rest--in the different blood leucocyte types (monocytes:n Mono; granulocytes:n GR; natural killer cells:n NK) and lymphocyte subsets (lymphocytes:n LY; lymphocytes T:n T; lymphocytes B:n B; lymphocytes T helper:n T4; lymphocytes T suppressor:n T8)--were as follows:n Mono:240%; n GR:170%; n NK:490%; n LY:220%; n T:200%; n B:190%; n T4:140%; n T8:190%. With the exception of n GR, n Leu decreased during recovery at a rate depending on the leucocyte type. The n T4/n T8 ratio, equal to 1 at rest, was reduced by about 40% during exercise. This ratio rose after exercise and reached a value equal to that measured at rest after 20 minutes recovery. In agreement with FERRY (1989), we concluded that exercise is accompanied by a selective mobilization of the different leucocyte types. The magnitude of this phenomenon and the kinetics of n Leu recuperation depend on cell types.

[Hemodynamic and respiratory effects of the perfusion of low-dose endotoxin in intact heparinized dogs]. / Effets hémodynamiques et respiratoires de la perfusion de faibles doses d'endotoxine chez le chien intact hépariné.

In the anesthetized dog, a low dose perfusion of endotoxin (50 ng X kg-1 X min-1) produces hemodynamic and metabolic perturbations generally similar to those clinically found in man during the hemodynamic phase of septic shock. These modifications are observed after about 30 minutes following the beginning of the perfusion. They constitute: 1) an arterial vasodilatation responsible for a hypotension without a significant modification of the cardiac output; 2) a drop in the left ventricular filling pressure; 3) a progressive metabolic acidosis; 4) a moderate arterial hypoxia that is independent of an alveolar hypoventilation. To these perturbations is added the contemporary development of a leucopenia associated with a thrombopenia. This mode of endotoxin administration seems to us to constitute a satisfactory experimental model for studying the circulatory injuries due to hyperdynamic septic shock.

[An animal model of hyperdynamic septic shock: hemodynamic effects of injection of low doses of endotoxin in the dog]. / Recherche d'un modèle animal du choc septique hyperdynamique: effets hémodynamiques de l'injection de faibles doses d'endotoxine chez le chien.

In anaesthetized dogs, low dose endotoxin perfusion (250 ng kg-1 min-1 during 20 min) resulted, after a delay of 15-40 min, in a decrease of mean arterial pressure (from 127 to 106 mm Hg), a transient increase in cardiac output (from 2.2 to 2.9 L/min), a fall of systemic vascular resistance (from 60 to 41 mm Hg L-1 min-1) and an increase in heart rate (from 109 to 156/min). This haemodynamic pattern is similar to the so called "hyperdynamic" initial phase of clinical septic shock.

[Hypotensive and edematogenic effects of carrageenan in the irradiated rat]. / Les actions hypotensive et oedématogène de la carragénine chez le rat irradié.

Iota carrageenan induces the same hypotensive effect in leucopenic and thrombopenic rats as in normal animals. This hypotensive activity depends on kininogen-kinins activation. In the irradiated rats, the inflammatory response to iota carrageenan is reduced. The blood cells are thus responsible of the major part of the late inflammatory effect. There is non parallelism between this hypotensive and the oedematogen activities of iota carrageenan in the rat.

[Activation of arachidonic acid]. / Activation de l'acide arachidonique.

Intravenous injection of arachidonic acid induces cardiovascular and respiratory effects due to its transformation into prostaglandins, This activation could take place not only in the platelets but also in the vacular wall. Platelet aggregation induced by arachidonic acid is not the main factor responsible of its cardiovascular actions.