Novel triazolium based 11(th) group NHCs: synthesis, characterization and cellular response mechanisms.

The novel NHC ligand precursor 1,4-bis(4-nitrobenzyl)-1H-1,2,4-triazol-4-ium bromide, [HTz((pNO2Bz)2)]Br, has been synthesized and used in the synthesis of the corresponding metal complexes M[Tz((pNO2Bz)2)]Br (M = Cu(I), Ag(I) or Au(I)). These compounds were characterized by several spectroscopic techniques including NMR and mass spectroscopy. The complete series of Au(I), Ag(I) and Cu(I) 1,2,4-triazole based NHC complexes has been synthesized aiming at a SAR study and at identifying the primary cellular targets accounting for their cytotoxic action. The cytotoxic properties of the NHC complexes have been assessed in various human cancer cell lines, including cisplatin sensitive and resistant cells, the most efficacious antiproliferative compound being Cu(I)-NHC, which was able to promote a growth inhibitory effect up to ten times higher than that promoted by cisplatin. A detailed analysis of molecular and cellular pharmacology allowed us to elucidate the role of the metallic core in determining the biological properties. In particular, gold(I) and silver(I) NHC complexes were found to be able to hamper mammalian thioredoxin reductase (TrxR) activity in human A431 cervical cancer cells, ultimately leading to a dramatic alteration of the cellular redox state and to the induction of cell death via apoptosis. Conversely, the copper NHC complex was found to be capable of inhibiting proteasome functionality thus determining the induction of a non-apoptotic cell death pathway.

Urinary volatile molecules vary in males of the 2 European subspecies of the house mouse and their hybrids.

Mice recognize other mice by identifying chemicals that confer a molecular signature to urinary marks. Such molecules may be involved in species recognition, and previous behavioral studies have related divergence of sexual preference between 2 subspecies of the house mouse (Mus musculus musculus and Mus musculus domesticus) to urinary odors. To characterize the differences between odors of males of the 2 subspecies and their first-generation offspring, the urinary volatile molecules were examined via gas chromatography coupled to mass spectrometry. Seven molecules were present in the samples from mice of at least one group. Their quantity varied among groups: M. m. domesticus showed a quantitatively richer panel of odorants in their urine when compared with M. m. musculus. The hybrids showed a more complex picture that was not directly related to one or the other parental subspecies. These quantitative differences may contribute to the specificity of the odorant bouquet of the 2 subspecies.

Effects of zinc supplementation on blood rheology during exercise.

We previously reported a higher blood viscosity at corrected hematocrit (45%) (explained by a higher value of erythrocyte rigidity) in football players with low serum zinc (Zn) and thus presumably Zn deficiency; subjects with low serum zinc had also an impairment in performance. This interventional study was undertaken in order to assess the effects of zinc supplementation (compared to placebo) on blood rheology and performance either at rest or during exercise. Ten male healthy volunteers (age: 26+/-1.3 yr; weight 67.9+/-2.24 kg; height 177+/-3 cm) received at random order either zinc (20 mg/day) and placebo, according to a double blind cross-over procedure, during seven days. In each case on the eighth day they performed a 25 min submaximal exercise-test. At rest blood viscosity at corrected hematocrit 45% (gamma = 1000 s(-1)) was lower after Zn (3.56+/-0.14 vs. 4.13+/-0.16 mPa.s, p = 0.009), explained by a lower RBC rigidity index 'k' according to Quemada's equation (1.65+/-0.07 vs. 1.84+/-0.08, p = 0.03). Hematocrit and plasma viscosity were unchanged, but RBC aggregation was decreased (laser retrodiffusion-derived aggregation time 'Ta' 3.52+/-0.51 vs. 2.75+/-0.59, p = 0.02). The increase in blood viscosity during exercise is lower after Zn than placebo. Blood viscosity at corrected hematocrit 45% remains unchanged during exercise after Zn, yet it increases after placebo. RBC rigidity index 'k' remains lower during exercise after Zn. The rating of perceived exertion (Borg's scale) at the 20th minute of exercise is lower after zinc (5.6+/-0.4 vs. 6.6+/-0.4, p = 0.008). This study confirms that Zn improves erythrocyte deformability, decreases the exercise-induced acute increase in blood viscosity, and improves exercise tolerance. Since Zn deficiencies are not unfrequent in sportsmen, these findings may be potentially relevant to sports nutrition.

[Is microalbuminuria, an early marker of clinical nephropathy, also a cardiovascular risk factor?]. / La micro-albuminurie, marqueur précoce d'atteinte rénale, est-elle aussi un facteur de risque cardiovasculaire?

Microalbuminuria is not only a predictor of diabetic nephropathy in type 1 diabetes, but also a potent marker of cardiovascular risk, especially in type 2 diabetes. Microalbuminuria also predicts cardiovascular morbidity in the general population. We describe semi-quantitative and quantitative methods for determination of low urinary excretion of albumin. Pathogenetic hypotheses common to both renal and endothelial dysfunction are discussed, suggesting that microalbuminuria may be a link between micro- and macroangiopathy. Improved glycemic control and antihypertensive treatment postpone and potentially prevent development of nephropathy in diabetic patients with microalbuminuria. These interventions must be instituted early in the development of diabetic nephropathy. In type 2 diabetes, prospective studies are needed to evaluate the precise impact of such a therapy on the cardiovascular risk.

The triphasic effects of exercise on blood rheology: which relevance to physiology and pathophysiology?

The life-extending effects of regular exercise are related to a decrease in both coronary and peripheral vascular morbidity, associated with some improvements in cardiovascular risk factors. A possible link between the beneficial metabolic and hemodynamic effects of exercise could be blood rheology, which is markedly affected by exercise. We propose here a description of the hemorheological effects of exercise as a triphasic phenomenon. Short-term effects of exercise are an increase in blood viscosity resulting from both fluid shifts and alterations of erythrocyte rheologic properties (rigidity and aggregability). Increased blood lactate, stress, and acute phase play a role in this process. Middle-term effects of regular exercise are a reversal of these acute effects with an increase in blood fluidity, explained by plasma volume expansion (autohemodilution) that lowers both plasma viscosity and hematocrit. Long-term effects further improve blood fluidity, parallel with the classical training-induced hormonal and metabolic alterations. While body composition, blood lipid pattern, and fibrinogen improve (thus decreasing plasma viscosity), erythrocyte metabolic and rheologic properties are modified, with a reduction in aggregability and rigidity. On the whole, these improvements reflect a reversal of the so-called "insulin-resistance syndrome" induced by a sedentary lifestyle. Since impaired blood rheology has been demonstrated to be at risk for vascular diseases, the hemorheologic effects of exercise can be hypothesized to be a mechanism (or at least a marker) of risk reversal. This latter point requires further investigation. The physiological meaning of the triphasic pattern of exercise-induced alterations of blood rheology is uncompletely understood, but increased blood fluidity may improve several steps of oxygen transfer to muscle, as clearly demonstrated in hypoxic conditions. Increasing evidence emerges from the literature, that blood fluidity is a physiological determinant of fitness.

Negative correlation between plasma fibrinogen and insulin sensitivity measured with the minimal model technique.

We aimed at investigating relationship between plasma fibrinogen and insulin sensitivity, which are two major determinants of metabolic Syndrome X (insulin resistance syndrome). We designed a prospective study of 27 non-diabetic, non-hypertensive subjects, presenting a wide range of body mass index BMI (10 men, 17 women; mean age+/-SEM: 35.9+/-2.2 years; BMI ranging from 21.1-45.2 kg/m2). Insulin sensitivity was assessed with the minimal model procedure, over a 180 min intravenous glucose tolerance test with iterative sampling. Fibrinogen levels were determined by the method of Clauss. The insulin sensitivity index SI (i.e., the slope of the dose-response relationship between insulin increased above baseline and glucose disposal) ranged from 0.0009 to 16 x 10(-4) min(-1)/(microU/ml), with a mean value of 4.76+/-0.73 x 10(-4). Mean values of plasma fibrinogen were 3.33+/-0.13 g/l, ranging from 2.21 to 5.07 g/l. There were highly significant negative correlations between SI and the level of plasma fibrinogen (r = -0.61, p = 0.0007) and between the basal effect of insulin BIE and plasma fibrinogen (r = -0.521, p = 0.005). Basal insulin was positively correlated to fibrinogen (r = 0.386, p = 0.046). When we analysed the data using partial correlation analysis, the negative relation between SI and fibrinogen was maintained independently from BMI (r = -0.45, p < 0.05). These data establish a strong negative association between insulin sensitivity and fibrinogen, involved in the increased cardiovascular risk of metabolic Syndrome X.

Serum zinc and blood rheology in sportsmen (football players).

We aimed at investigating relationships between zinc status, blood rheology and blood glucose during exercise. Twenty-one professional football players underwent a triangular maximal exercise test on cycloergometer, with progressively increasing work loads until VO2max. On the whole these subjects had a low serum zinc because nine of them had a hypozincemia (0.54 +/- 0.01 mg/l) which suggested a zinc deficiency. Subjects with low serum zinc were able to perform a lower power output (123 +/- 8.71 vs. 166.27 +/- 14.84 watts, p = 0.029) and exhibited a higher increase in blood lactate during exercise (7.51 +/- 0.81 vs. 5.57 +/- 0.33 mmol/l, p = 0.024) resulting in a lower 2 mmol lactate threshold (44.7 +/- 3.9% vs. 58.9 +/- 4.8% of maximal power output, p = 0.04). They were less able to maintain their plasma glucose and exhibited a tendency towards hypoglycemia (p = 0.0153). Hypozincemia was associated with a higher viscometric RBC rigidity index (p = 0.0009), and this index was negatively correlated to serum zinc (r = -0.68, p = 0.7 x 10(-3)). Blood viscosity at high shear rate (MT90 viscosimeter) corrected for hematocrit (45%) remained higher during exercise in these hypozincemic subjects (p = 0.003). This study suggests that zinc status may influence blood rheology during exercise, either by its direct action on RBC flexibility (demonstrated in vitro) or by its effect on lactate accumulation which may in turn modify erythrocyte fexibility.

Metabolic and hormonal responses during repeated bouts of brief and intense exercise: effects of pre-exercise glucose ingestion.

We investigated metabolic and hormonal responses during repeated bouts of brief and intense exercise (a force-velocity test; Fv test) and examined the effect of glucose ingestion on these responses and on exercise performance. The test was performed twice by seven subjects [27 (2) years] according to a double-blind randomized crossover protocol. During the experimental trial (GLU), the subjects ingested 500 ml of glucose polymer solution containing 25 g glucose 15 min before starting the exercise. During the control trial (CON), the subjects received an equal volume of sweet placebo (aspartame). Exercise performance was assessed by calculating peak anaerobic power (W(an,peak)). Venous plasma lactate concentration increased significantly during the Fv test (P < 0.001), but no difference was found between CON and GLU. Blood glucose first decreased significantly from the beginning of exercise up to the 6-kg load (P < 0.001) and then increased significantly at W(an,peak) and for up to 10 min during the recovery period (P < 0.001) in both CON and GLU. Insulin concentrations decreased significantly in both groups, but were higher at W(an,peak) in GLU compared with CON (P < 0.05). Glucagon and epinephrine did not change significantly in either group, but epinephrine was significantly lower in GLU after glucose ingestion (P < 0.05) and at W(an,peak) (P < 0.05). W(an,peak) was not significantly different between CON and GLU. In conclusion, blood glucose and insulin concentrations decreased during repeated bouts of brief and intense exercise, while blood lactate concentration increased markedly without any significant change in glucagon and epinephrine concentrations. Glucose ingestion altered metabolic and hormonal responses during the Fv test, but the performance as measured by W(an,peak) was not changed.

[Interrelation of visceral fat and muscle mass in non insulin-dependent diabetes (type II): practical implications]. / Interrelation de la masse grasse viscérale et du muscle dans le diabète non insulino-dépendant (type II): implications pratiques.

Insulin resistance, which is found in 85-95% of non-insulin-dependent diabetes mellitus (NIDDM) patients, results from three factors: genetic background (which has been widely investigated), nutritional status (mostly obesity and fat distribution) and exercise. Upper body obesity, which can be found in 85% of these subjects, can increase muscular insulin resistance through several mechanisms, the best known being a free fatty acid-induced decrease in intracellular free CoA/acylCoA that inhibits the stimulatory effect of insulin on glycolysis, glucose transport across cell membrane, and glycogen storage. However, muscle insulin resistance in NIDDM exists before adiposity and is likely to induce it. Actually, muscles of subjects at risk for NIDDM exhibit a very early defect in both glycogen storage ability and free fatty acid oxidation capacity that can impair fuel utilization and increase fat storage. Regular exercise induces muscular metabolic changes which can compensate for those diabetogenic defects and thus prove useful in the management of NIDDM. Moreover, exercise has been shown to prevent subjects at risk for NIDDM from developing overt diabetes.

Increased insulin sensitivity and basal insulin effectiveness in postprandial reactive hypoglycaemia.

Glucose clamp experiments have shown that patients with reactive postprandial hypoglycaemia (PRH) frequently have an increased glucose disposal, but the relative involvement of insulin sensitivity (SI) and glucose effectiveness (Sg) in this process remains unknown. The minimal model approach was used to compare 13 patients in whom moderate reactive hypoglycaemia ( < 3.3 mmol) had been previously diagnosed and 13 matched controls. The intravenous glucose tolerance test (IVGTT, 0.5 g/kg glucose IV) with 0.02 U/kg insulin given at the 19th min and frequent sampling over 180 min shows that PRH patients exhibit a higher glucose tolerance coefficient Kg (2.99 +/- 0.26 vs 2.19 +/- 0.12; P < 0.02), higher SI [22.9 +/- 6.4 vs 7.18 +/- 0.14 min-1/(microU/ml). 10(-4); P < 0.01] and higher Sg (3.84 +/- 0.35 vs 2.92 +/- 0.79 min-1. 10(-2); P < 0.05). The increase in Sg is explained by an increase in its component basal insulin effectiveness (BIE: 1.2 +/- 0.27 min-1.10(-2) in PRH subjects vs 0.58 +/- 0.07; P < 0.05) rather than an increase in Sg at zero insulin. The increase in BIE results from the high values of SI. In 4 PRH subjects SI and Sg were within the normal range, and the increase in Kg evidenced in the 9 others was explained by an increase in SI alone in 3 cases, in Sg alone in 1 case, and both SI and Sg in 5 cases. Thus, in sedentary subjects, the previously reported rise in tissue glucose assimilation is mainly explained by an increased insulin-mediated glucose disposal rather than non-insulin-mediated glucose disposal.

Endogenous oploid peptides stimulate post-exercise insulin response to glucose in rats.

Exercise is associated with profound changes in glucose metabolism and insulin secretion. Endogenous opioid peptides may be involved in these metabolic adaptations. To gain insights into this hypothesis, we studied the effects of the opioid antagonist naloxone on the insulin response to glucose after a 2.5 h exercise bout, either by means of an intravascular glucose tolerance test in male Wistar rats or from rat islets of Langerhans isolated just after exercise. There was a tenfold increase in plasma beta-endorphin concentrations (9.8 +/- 2.1 vs. 114.2 +/- 22.0 fmol/ml, p < 0.001) in animals killed immediately after exercise. The in vivo post-exercise peak insulin response to glucose was markedly reduced compared to resting controls (p < 0.01). Interestingly, naloxone (10 mg/kg) still further decreased the insulin response compared to saline injected exercised rats (p < 0.05), but did not alter the response from resting animals. The post-exercise insulin response to 8.3 mM glucose was significantly reduced compared to resting rat islets (p < 0.05) and was further inhibited when naloxone (10 mu M) was added to the culture medium (p < 0.05). In another experiment, we also tested the effect of 10(-8) and 10(-6) M beta-endorphin on control islets. Both concentrations of beta-endorphin significantly increased the islet insulin response to 8.3 mM glucose (p < 0.05) and this effect was completely blocked by naloxone. These results suggest that endogenous opioid peptides participate in the physiological adaptation to exercise stress in maintaining post-exercise insulin response to glucose.

[Blood viscosity is correlated with insulin resistance]. / La viscosité sanguine est corrélée à l'insulino-résistance.

The insulin resistance syndrome (or syndrome X) is a cluster of symptoms (dyslipidemia, impaired glucose tolerance, overweight, hypertension) associated with a higher risk of atherosclerosis. It has been suggested that hemorheological abnormalities, often found in association with most of these symptoms, may be a part of this syndrome, and possibly play a role in the circulatory abnormalities. In 22 nondiabetic women (20-54 years) presenting a wide range of body mass index (from 20 to 48 kg/m2), insulin sensitivity was assessed with the minimal model procedure, over a 180 min intravenous glucose tolerance test with frequent sampling. The insulin sensitivity index SI (i.e. the slope of the dose-response relationship between insulin increased above baseline and glucose disposal) ranges between 0.1 and 20.1 x 10(-4) min-1/microU/ml) i.e all the range of insulin sensitivity. SI was negatively correlated with blood viscosity (r = -0.530 p < 0.02), body mass index (r = 0.563 p < 0.01) and baseline insulinemia (r = 0.489 p < 0.05). These correlations were independent of each other and were not explained by relationships between SI and fibrinogen or blood lipids. Thus, blood fluidity is correlated with insulin sensitivity when it is measured with an accurate technique, suggesting that blood hyperviscosity is a symptom of insulin resistance that might be involved in the cardiovascular risk of this syndrome.

Influence of short-term submaximal exercise on parameters of glucose assimilation analyzed with the minimal model.

After exercise, glucose uptake in tissues increases by insulin-dependent and -independent mechanisms. We evaluated whether these two effects of exercise on glucose disposal can be detected with the minimal model technique. Seven healthy volunteers were submitted at random order to two frequently sampled intravenous glucose tolerance test (FSIVGTTs), one at rest and the other 25 minutes after a 15-minute exercise test. This exercise included 5 minutes of increasing workload on a cycloergometer followed by 10 minutes at 85% of the maximal theoretic heart rate. Bergman's minimal model of insulin action was used to analyze the two FSIVGTTs and produced the following parameters: coefficient of glucose tolerance (Kg), ie, the slope of the exponential decrease in glycemia between 4 and 19 minutes after intravenous glucose; insulin sensitivity (Sl); and glucose effectiveness at basal insulin (Sg). Sg was divided into its two components: basal insulin effectiveness ([BIE] Sl x basal insulin) and glucose effectiveness at zero insulin ([GEZI] Sg-BIE). After the exercise bout, subjects had an increased Kg (3.44 +/- 0.44 v 2.06 +/- 0.28 x 10(-2).min-1, P < .02), Sl (11.43 +/- 1.27 v 6.23 +/- 0.97 x 10(-4) microU/mL.min-1, P < .01), and Sg (4.40 +/- 0.55 v 2.81 +/- 0.36 x 10(-2).min-1, P < .02). The increase in Sg was mainly explained by a 60% increase in GEZI (3.6 +/- 0.57 v 2.25 +/- 0.36 x 10(-2).min-1, P < .02), but also by an increase in BIE (0.80 +/- 0.12 v 0.47 +/- 0.08 x 10(-2).min-1, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Protective effect of gamma-hydroxybutyrate and nicotinamide on low-dose streptozotocin-induced diabetes in mice.

The purpose of this study was to investigate the effect of a treatment by gamma-hydroxybutyrate (GHB) and nicotinamide (NA) on low-dose streptozotocin (STZ)-induced diabetes in mice. Mean plasma glucose level was significantly elevated in mice given STZ by day 12 after the first STZ injection compared to controls (15.0 +/- 4.7 vs 8.0 +/- 1.6 mmol/l, p < 0.001) and 100% of the animals were severely diabetic by day 18. Plasma glucose levels remained in the normal range and no diabetic values were found in mice treated with combined treatment by GHB and NA for 25 days. However, hyperglycemia and glycosuria appeared within one week after discontinuation of the treatment. Treatment by either GHB or NA alone had only a slight and transient effect in preventing hyperglycemia. In vitro experiment on isolated pancreatic islets demonstrated that STZ-induced loss of insulin response to glucose was also counteracted by incubation with GHB and NA (Peak insulin response to 16.4 mM glucose: 0.69 +/- 0.31 vs 3.03 +/- 0.67 microU/islet/min), but not by GHB or NA alone. These results indicate that GHB and NA have complementary effects in preventing STZ-induced beta cell damage both in vivo and in vitro. This should be taken into account for future preventive strategies in human insulin-dependent diabetes mellitus.

Evaluation of a standardized hyperglucidic breakfast test in postprandial reactive hypoglycaemia.

The oral glucose tolerance test is not specific for diagnosing postprandial reactive hypoglycaemia, since it too frequently induces low blood glucose values in subjects who have never complained of symptoms of this. By contrast, the mixed meal tests are deceptive for this purpose because they do not induce hypoglycaemia in subjects who have complained of of hypoglycaemic symptoms. We investigated the frequency of hypoglycaemia after a standardized hyperglucidic breakfast test in three groups of subjects:group A, 43 control subjects; group B, 38 postprandial reactive hypoglycaemic patients; group C, 1193 asymptomatic subjects undergoing assessment of glycoregulation. In the 38 subjects with suspected reactive hypoglycaemia the mean blood glucose nadir was 3.48 +/- 0.08 mmol/l, i.e. lower than in control subjects (4.83 +/- 0.13 p < 0.0001). Blood glucose levels less than 3.3 mmol/l were found in 47.3% of subjects with suspected postprandial reactive hypoglycaemia (group B), i.e more frequently than in control subjects (group A: 2.2% p = 1.6 x 10(-6)) and asymptomatic subjects (group C: 1% p = 8 x 10(-22)). This markedly higher frequency of low blood glucose values in subjects with postprandial symptoms compared with control and asymptomatic subjects suggests that this test detects a tendency to hypoglycaemia after a standardized hyperglucidic breakfast. Since this test mimics average French eating habits, the results suggest that the patients undergo such symptoms in their everyday life, and that the hyperglucidic breakfast test is a simple alternative to ambulatory glucose sampling for diagnosis of postprandial reactive hypoglycaemia.

Effects of zamic as a means for zinc supplementation in growing children.

We investigated the effects of zinc supplementation in case of moderate growth retardation in which GH treatment could not be used. Zamic (ZA, an association containing arginine, L-methionine, and zinc; from Aguettant pharmaceuticals) was compared with arginine aspartate (AA) (5 g) in a crossover randomized trial (6 mo of each treatment at random order over 1 yr). We present preliminary results of 24 children who completed the study (3 girls, 21 boys, age 9-13 yr). Subjects had to be prepubertal, with no GH deficiency diagnosed. In 15 subjects growth velocity was lower than 5 mm/mo: In this case ZA improved growth velocity (rising from 3.105 +/- 0.229 to 5.4 +/- 0.69 mm/mo p < 0.01), whereas the effect of AA was not significant. The increase in growth velocity was higher with ZA (+2.44 +/- 0.657 mm/mo) than AA (+0.438 +/- 0.450 mm/mo) p < 0.05. These results suggest that ZA is more efficient than AA, consistent with the hypothesis that zinc needs are increased in those children in this period of life.

Effects of naloxone opiate blockade on the immunomodulation induced by exercise in rats.

The purpose of this study was to examine the possible involvement of the endogenous opiate system in the changes in immune competence induced by isolated exercise. Male untrained rats were subjected to a 2.5 hours swimming exercise bout. Animals were killed 15 min after the end of the exercise. The concentration of leukocytes, lymphocytes, monocytes and granulocytes and T4 (T-helper), T8 (T-suppressor/cytotoxic), interleukin-2 receptor (IL-2R) and transferrin receptor (TrfR) positive lymphocytes were determined both in peripheral blood and spleen by flow cytometric analysis. Exercise resulted in a significant decrease in 1) blood lymphocyte and splenic granulocyte number (p < 0.05), 2) blood and splenic T4 positive lymphocytes and T4/T8 ratio (p < 0.05), and 3) blood and splenic IL-2R and TrfR positive lymphocytes (p < 0.05). The injection of the opiate blocker naloxone to exercising rats induced a decrease in the concentration and proportion of T8 positive lymphocytes, thereby restoring a normal T4/T8 ratio both in peripheral blood and spleen. Naloxone had no effect in control animals. The concentration and proportion of IL-2R and TrfR positive lymphocytes were not affected by naloxone. The mechanisms of the immunomodulation induced by isolated intense exercise are unclear. These data suggest that endogenous opiates participate in the alteration of cell-mediated immunity associated with exercise by modulating the T8 (suppressor/cytotoxic)-cell activity.

In vitro influence of zinc and magnesium on the deformability of red blood cells artificially hardened by heating.

Trace elements have been shown to improve red blood cell (RBC) deformability: zinc in sickle cell disease and magnesium in an in vitro model of chemically rigidified erythrocytes. In this study, we investigated the effect and the influence of incubation time of zinc or magnesium on an in vitro model of rigidified RBCs by heating. Erythrocyte rigidity was determined by viscosimetry at high shear rate by a falling ball viscosimeter MT 90. In the first part of the study, six normal volunteers participated. Viscosimetry was performed on native blood before and after heating the sample for 10 min at 50 degrees C. Therefore, increasing concentrations of zinc gluconate (final concentration: 0.5-4 g/L) or isotonic NaCl as control medium were added to the sample. Heating induced a twofold increase in all indices of RBC rigidity (p < 0.05). At all these concentrations of zinc, a highly significant, dose-related fluidifying effect was observed (40-70%): this effect was immediately obtained and did not change over 60 min. Even at the highest concentration, recovery was not complete. In the second part of the study, we studied magnesium's effects on blood. In a first protocol, whole blood was rigidified by heating at 56 degrees C for 10 min, and the correcting effect of 5 min of incubation at 37 degrees C of RBCs in 150 mmol/L NaCl, MgSO4, magnesium acetate, and magnesium gluconate was investigated. In a second protocol, the same incubation with NaCl and magnesium salts was made on blood that had not been previously heated.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum zinc in highly trained adolescent gymnasts.

Serum zinc was measured in 20 adolescent gymnasts (9 boys, 11 girls, age 12-15 yr) explored for detecting possible adverse effects of intense training on pubertal maturation and growth. They had low serum zinc (0.599 +/- 0.026 mg/L) when compared to matched control sedentary children (n = 118 mean 0.81 +/- 0.014 p < 0.001). Girls had lower zinc than boys (0.557 +/- 0.023 vs 0.651 +/- 0.044 p < 0.001). Zinc was correlated to isometric adductor strength (r = 0.468 p < 0.05). Children with serum zinc < 0.6 mg/L had lower insulin-like growth factor binding protein 3 than others (2.326 +/- 0.264 vs 2.699 +/- 0.12 p < 0.01). Thus, zinc is lowered in trained adolescent gymnasts and even lower in females. This reduction could play some role in abnormalities of puberty, growth, or muscular performance.