Fatal lactic acidosis in malignant histiocytosis.
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Acidosis, Lactic↗
Biomedical subjects
M Bernier
Publications and source records attributed to M Bernier.
Reperfusion-induced arrhythmias and oxygen-derived free radicals. Studies with "anti-free radical" interventions and a free radical-generating system in the isolated perfused rat heart.
We have assessed, whether six agents, that either inhibit free radical formation or scavenge free radicals once they are produced, can reduce the incidence of reperfusion-induced arrhythmias, whether a free radical-generating system (FeCl3 X adenosine diphosphate) can increase the incidence of reperfusion-induced arrhythmias, and whether "anti-free radical" interventions can reduce reperfusion rhythm disturbances caused by the addition of FeCl3 X adenosine diphosphate. With the isolated, perfused rat heart (n = 15 in each group), inclusion of L-methionine (1 and 10 mM), superoxide dismutase (2.5 X 10(4) and 1 X 10(5) U/liter), catalase (5 X 10(4), 5 X 10(5), and 1 X 10(6) U/liter), mannitol (50 mM), glutathione (10 microM), or desferrioxamine (150 microM) significantly reduced the incidence of reperfusion-induced ventricular fibrillation and, in many cases, the incidence of reperfusion-induced ventricular tachycardia. The mean duration of sinus rhythm during reperfusion was also increased significantly. Perfusion of hearts with boiled superoxide dismutase (1 X 10(5) U/liter) or boiled catalase (1 X 10(6) U/liter) did not decrease arrhythmias. Conversely, under conditions where, in the control group, the incidence of reperfusion arrhythmias was lowered by increasing perfusate potassium to 6.5 mM, the addition of the free radical-generating system FeCl3 X adenosine diphosphate (0.1 microM X 1 microM) to the perfusion fluid increased dramatically the incidence of reperfusion-induced ventricular fibrillation and tachycardia. Simultaneous perfusion with FeCl3 X adenosine diphosphate and superoxide dismutase (1 X 10(5) U/liter), catalase (1 X 10(6) U/liter), mannitol (50 mM), methionine (10 mM), or desferrioxamine (150 microM) again reduced the incidence of reperfusion-induced arrhythmias and increased the duration of normal sinus rhythm during the reperfusion phase. Thus, addition of six "anti-free radical" interventions reduced the incidence of reperfusion-induced arrhythmias, addition of a free radical-generating system increased the incidence of reperfusion-induced arrhythmias, and simultaneous perfusion of the hearts with FeCl3 X adenosine diphosphate and "anti-free radical" interventions again reduced reperfusion rhythm disturbances. These results are further evidence supporting the hypothesis that oxygen-derived free radicals play an important role in the genesis of reperfusion-induced arrhythmias.
Animals↗
Regulation of gonadotropin receptors on cultured porcine Leydig and Sertoli cells: effect of potassium depletion.
We have examined the role of the NaK-ATPase pump activity on the ligand-induced down-regulation of gonadotropin receptors in cultured porcine Leydig and Sertoli cells. In both cells, inhibition of the NaK pump by ouabain produced a depletion of intracellular K+ levels (ID50, 10(-7) M) after a lag period of about 8 h. In the absence of ligand, the number of FSH receptors in ouabain-treated Sertoli cells was unaffected or slightly reduced, whereas a 2-fold increase in the number of human CG (hCG)/LH receptors with small changes in the binding affinity was observed in Leydig cells treated by ouabain. The effect of ouabain was dose dependent. Differences were also observed in the down-regulation process of gonadotropin receptors in ouabain-treated cells. The hCG-induced receptor loss in Leydig cells was completely reversed by ouabain whereas the drug had no effect on ligand-induced loss of FSH receptors in Sertoli cells. Similar results were observed when the cells were incubated in K+-free medium. Kinetics studies with labeled hCG have shown that ouabain treatment slows down significantly the rate of [125I]iodo-hCG internalization (t 1/2, 18 h; control cells, t 1/2, 6 h), but had no effect on the degradation of internalized hormone. The internalization of receptor-bound [125I]iodo-hCG was also reduced when Leydig cells were incubated in K+-free medium, but was restored when this medium was supplemented with rubidium. The influence of the NaK pump on the receptor regulation of a ligand common to both types of cells, such as epidermal growth factor, was studied under the same experimental conditions. Neither ouabain nor K+-free medium were able to prevent the epidermal growth factor-induced reduction of receptor levels in Leydig and Sertoli cells. Thus, it appears that modulation of ligand-induced receptor loss by depletion of cellular K+ levels is not dependent on the cell type, but on the ligand-receptor complex. The data also show a striking difference in the dynamics of gonadotropin-receptor interaction of two structurally related hormones.
Animals↗
[Effects of insulin and somatomedin C on the function of cultured Leydig cells].
Porcine cultured Leydig cells (LC) lose hCG receptors and hCG responsiveness (cAMP and testosterone) when they are cultured for three days in a defined medium without insulin or somatomedin C (Sm-C) (Insulin-like growth factor I). In the presence of insulin (50 ng/ml) or of Sm-C (10 ng/ml) the loss of the hCG receptor number and the decreased cAMP response to hCG were prevented, but the steroidogenic response to hCG was only partially prevented. This parameter became normal when cells were pretreated with either Sm-C (10 ng/ml) plus insulin (50 ng/ml) or with insulin alone at high concentrations (5 micrograms/ml). These results indicate that both Sm-C and insulin acting through their own receptors increase Leydig cell steroidogenic capacity by increasing hCG receptor number and improving some step beyond cAMP formation.
Animals↗
Age- and sex-specific prevalence of scoliosis and the value of school screening programs.
A prevalence study of idiopathic scoliosis was conducted among 29,195 children of a community health district in the province of Quebec. The study was designed to determine whether a permanent screening program for idiopathic scoliosis was justified. The prevalence of the condition among school children aged 8 to 15 years was 42.0 per 1,000 in the screened population, 51.9 per 1,000 among girls, and 32.0 per 1,000 among boys. The positive predictive value of the bending test is estimated as 42.8 per cent for scolioses of 5 degrees or more; it is only 6.4 per cent when curves of 15 degrees or more are considered. The average cost of finding one child with a scoliosis of 5 degrees or more is $194. Mass screening for idiopathic scoliosis does not seem to be justified in the present state of knowledge of the disease.
Adolescent↗
Na+ transport by brush border membrane from rat kidney.
Na+ uptake was measured in brush border membrane isolated from rat kidney cortex. In the presence of 100 mM NaCl gradient, Na+ equilibrated across the membranes within 30 minutes, but uptake was linear only for the first 10 seconds. Total uptake could be analysed in terms of a diffusion component and a saturable component (Kt = 5 mM, Jmax = 0.62 pmol/microgram prot/s). Uptake at 1 mM NaCl was found to be inhibited at 60% by amiloride; stimulation of uptake by pH gradient (inside greater than outside) supports the functioning of a Na+-H+ antiport. Uptake at 100 mM NaCl was insensitive to amiloride in the absence of pH gradient. The influence of anions on Na+ uptake was in agreement with known permeabilities for generation of electrical potentials (Thiocyanate greater than chloride greater than gluconate) and was observed at 100 mM Na+ but not at 40 microM. These results suggest that rat renal brush border membrane vesicles are leaky towards Na+ and present a permeability coefficient for Na+ much higher than what is expected from the in vivo conditions.
Amiloride↗
Angiotensin II: dependence of hormone affinity on the electronegativity of a single side chain.
Structure-activity studies on rabbit aorta of angiotensin II analogues have suggested a possible relationship between the electronegativity of the aromatic side chain in position 4 (Tyr) and the observed affinity. In order to test this hypothesis, several other analogues modified in position 4 have been prepared, and all available analogues were tested in three bioassays: in vitro on rabbit aorta strip, in vivo on the rat blood pressure, and the binding assay on beef adrenocortical membranes. In all three bioassays the postulated correlation has confirmed that angiotensin II affinity depends inversely on the electronegativity of the aromatic side chain in position 4.
Adrenal Cortex↗
Effect of glucocorticoids on testosterone production by porcine Leydig cells in primary culture.
For this study, purified immature porcine Leydig cells in primary culture were used. After 2 days of culture, the cells were incubated with dexamethasone (5 X 10(-9), 1 X 10(-7) M) for various periods of time (3-45 h). The media were discarded and treatment was repeated with or without the addition of human chorionic gonadotropin (HCG, 10 mIU/mL) for 3 h. Dexamethasone (10(-7) M) decreased testosterone production of HCG-treated cells (up to 40%) in a time-dependent fashion while the lower dose was ineffective. The effect of varying doses (10(-8) and 10(-6) M) of natural glucocorticoids (corticosterone, cortisol) or synthetic glucocorticoids (triamcinolone, triamcinolone acetonide, betamethasone, dexamethasone) and that of a synthetic progestin (R-5020) on cultured Leydig cells was also studied. After 18 h of preincubation, the various synthetic but not the natural steroids nor R-5020, were able to decrease testosterone production of control and HCG-treated cells by 20-40%. Of a number of other hormonal and nonhormonal substances studied at concentrations of 10(-9)-10(-5) M, only lysine8-vasopressin at a concentration of 10(-6) M was able to inhibit testosterone production by these cells. These results indicate that dexamethasone and other synthetic glucocorticoids, and to a lesser degree lysine8-vasopressin, may exert a direct inhibitory effect on testosterone production by purified porcine immature Leydig cells in vitro.
Animals↗
The 3 beta-hydroxysteroid dehydrogenase activity of cultured porcine Leydig cells in primary culture.
Previous studies have shown that there is a spontaneous progressive increase in human chorionic gonadotropin (HCG)-stimulated testosterone (T) production by immature porcine Leydig cells during primary culture for 3 days, whereas basal T production is unaltered. Preliminary data indicated that during this time, there was an increase in the activity of the 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). The purpose of the present study was to further characterize this increase. 3 beta-HSD was assayed by measuring the conversion of tritiated dehydroepiandrosterone (DHEA) to androstenedione in the presence of NAD+. A ninefold increase in activity occurred between days 1 and 2 and only twofold between days 2 and 3. A 5- to 20-fold increase of the apparent maximum velocity of the enzyme was observed after 3 days of culture while the apparent Km remained unchanged. Cycloheximide treatment (150 ng/mL) completely abolished this spontaneous increase in enzyme activity. In parallel experiments, the stimulatory effect of HCG on T and DHEA production was inhibited by cycloheximide treatment by 90% and 60%, respectively, whereas basal T production was not affected. These results suggest that the spontaneous increase of 3 beta-HSD activity in primary cultures of porcine Leydig cells is secondary to de novo protein synthesis and that this phenomenon may be partially responsible for the increased responsiveness of these cells to HCG during the culture period.
3-Hydroxysteroid Dehydrogenases↗
Androgen production in primary culture of immature porcine Leydig cells.
The present paper examines the steroidogenic responsiveness of immature porcine Leydig cells in primary culture. Both testosterone (T) and dehydroepiandrosterone sulfate (DHAS) secretion were measured under basal conditions and after stimulation with human chorionic gonadotropin (hCG) (25 ng/ml). In medium supplemented with insulin, transferrin, epidermal growth factor (3H) and 0.1% calf serum, cells survived 3-5 days in culture. The production of steroids (under hCG stimulation) is poor on day 0-1 of the culture. On day 2-4 basal T and DHAS levels are 1.9 and 17.0 ng/10(6) cells/24 h. The addition of hCG stimulated T and DHAS production 19- and 6-fold respectively and the average productions were 37 and 109 ng/10(6) cells/24 h. Increasing the serum to 0.5% did not change the viability of the cultures, but increased hCG stimulated T and DHAS production (183 and 188 ng/10(6) cells/24 h). The addition of alpha-tocopherol (vitamin E) to 0.1% calf serum led to a 4-fold increase in stimulated T production (142 ng/10(6) cells/24 h) and maintained full cell viability for more than 5 days. Measurement of 3 beta-ol steroid dehydrogenase activity indicates that the amount of enzyme is 4 times higher at day 2 than at day 0 and 1 (with or without hCG), suggesting a spontaneous maturation of the cells in culture. This might explain the increased T production with time in culture. In cumulative experiments (24 h) the cells do not seem to be desensitized to hCG stimulation following prolonged exposure to 25 ng hCG since the daily steroid production is increasing with time in culture. However, kinetic studies show that steroidogenesis is not linear over a 24 h period. In cumulative experiments the steroid production stops between 12 and 16 h following hCG exposure (5 and 100 ng/ml) and resumes following a medium change. These results suggest that some inhibitory compounds are accumulated in the medium and are controlling the Leydig cell function. Moreover high doses of hCG (100 ng/ml) result in a lower production of steroids and an earlier plateau in the case of DHAS. These results demonstrate that porcine Leydig cells can live and differentiate in hormone- and vitamin-supplemented medium and that auto-feedback mechanisms inhibiting steroid accumulation take place under in vitro conditions.
3-Hydroxysteroid Dehydrogenases↗
Studies with purified immature porcine Leydig cells in primary culture.
The steroidogenic capacity of purified immature porcine Leydig cells in culture was studied over several days. The cells were obtained by fractionating crude testicular interstitial cell suspensions on a discontinuous Percoll gradient (d = 1.037, 1.042, 1.052, 1.098 g/ml), and characterized by specific binding of 125I-human chorionic gonadotropin (hCG), testosterone (T) and cyclic adenosine 3':5'-monophosphate (cAMP) production in response to hCG, and the enzymatic determination of delta 5-3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity. The Leydig cells were recovered in a density band between 1.052-1.068 g/ml and grown in a chemically defined medium (Mather et al., 1981). In the absence of hCG, T production was low throughout the 6 days of culture. However, in response to hCG (10 mIU/ml), the cultured Leydig cells showed a progressive increase in T synthesis, which reached a maximum at Days 3-4. 8-Br-cAMP (1 mM) induced a comparable rise in T production to that obtained with hCG throughout the culture period. In contrast, 8-Br-cAMP induced a near maximal increase in dehydroepiandrosterone (DHEA) production from Day 1. This paper demonstrates that purified immature porcine Leydig cells in primary culture are a valuable model to study the ontogeny of Leydig cell function.
3-Hydroxysteroid Dehydrogenases↗
False diagnosis of legionellosis.
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Diagnostic Errors↗
Stress-induced testicular hyposensitivity to gonadotropin in rats. Role of the pituitary gland.
The time course of stress-induced testicular hyposensitivity to gonadotropins was studied in hypophysectomized or naloxone-treated rats exposed to various periods of immobilization. Blood was collected from a chronically indwelling intra-atrial catheter every hour for luteinizing hormone (LH) and testosterone (T) measurement. Eight hours of immobilization completely suppressed T secretion without significant effect on LH. Human chorionic gonadotropin (hCG, 5 IU/rat, i.m.) induced a marked increase in plasma T levels in normal control groups 3 h post-injection while in immobilized rats the response was completely abolished, even after only 30 min of stress. In hypophysectomized rats, as expected, plasma T levels were undetectable, but, contrary to results obtained in normal animals, hCG induced a similar increase of plasma T levels both in control and stressed rats. Immobilization stress failed to inhibit plasma T values in hypophysectomized rats pretreated for 4 days with human menopausal gonadotropin (hMG) + hCG, while it did so in similarly treated normal animals. Naloxone induced a rise of plasma LH and T levels in control rats, but did not antagonize the stress-induced fall of plasma T concentration. In all groups, steroid testicular content mimicked variations of plasma T values. In particular, in stressed animals the lack of accumulation of testicular 17-hydroxyprogesterone probably reflected a normal activity of 17-20 lyase. These results indicate that stress induces very rapidly a state of Leydig cell hyposensitivity to gonadotropins and a blockade of T biosynthesis. The causal relationship between the two effects is presently not clear but these events seem to be due to stress-induced release of an inhibitory factor of pituitary origin other that endorphin.
Adrenocorticotropic Hormone↗
Effects of chronic intermittent immobilization stress on rat testicular androgenic function.
In rats, chronic intermittent immobilization stress induced a drastic fall in the plasma concentration and testicular content of testosterone (T) without detectable changes in plasma LH values. In vitro basal T production by interstitial cell-enriched preparations from stressed rats and the responses to hCG, dibutyryl cAMP, or choleratoxin were suppressed, while cAMP production was not modified. The increase in plasma T concentrations in control animals was identical after the in vivo injection of 5, 10, or 50 IU hCG, while stressed rats failed to respond to 5 IU, but showed a response similar to that of control animals with 10 and 50 IU. These results suggest that chronic intermittent immobilization stress decreases Leydig cell sensitivity to gonadotropins.
Animals↗
[Statistical note on 300 cases of insomnia treated at a spa].
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Age Factors↗
[Electron microscopy study of giant cells of the myometrium during the gestation period].
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Female↗
In vitro activity of clarithromycin and its 14-hydroxy-metabolite against 203 strains of Haemophilus influenzae.
The in vitro activity of clarithromycin alone and in combination with its primary human metabolite, 14-hydroxy-clarithromycin, was determined against 203 strains of Haemophilus influenzae. Microdilution broth MICs and MBCs of both clarithromycin and 14-hydroxy-clarithromycin were determined. The clarithromycin MIC50 was 4 mg/l and the MIC90 was 8 mg/l. The hydroxy metabolite was 2-4-fold more active with an MIC50 and MIC90 of 2 mg/l. The MBCs were equal to the MICs. The microbicidal effect of combinations of clarithromycin and 14-hydroxy-clarithromycin was tested using a microdilution checkerboard technique and the fractional inhibitory index was calculated. The combination was additive in 92% and synergistic in 8% of all strains of H. influenzae tested; no antagonism was found. The results were independent of the site of isolation of the strain or presence of beta-lactamase. These findings suggest the potential clinical utility of clarithromycin for the treatment of H. influenzae infections.
Bacterial Typing Techniques↗
Bactericidal activity of cefpirome (HR 810) against 513 gram-negative bacteria isolated from blood of septicemic patients.
The profile of antibacterial activity of cefpirome was compared with that of nine other antimicrobial agents against 513 gram-negative bacteria isolated from septicemic patients. All strains were evaluated for their sensitivity by disc diffusion and broth dilution tests (MIC and MBC). Cefpirome was compared to cefazolin, cefuroxime, ceftazidime, ceftriaxone, aztreonam, imipenem, ticarcillin, tobramycin and ciprofloxacin. Among the five cephalosporins tested in this study, cefpirome was the most active against all isolates. The MIC50 and MIC90 of eight isolates of Acinetobacter calcoaceticus were 2 and 4 mg/l and those of 89 Pseudomonas aeruginosa were 2 and 8 mg/l, respectively. The MIC90 values of cefpirome for all other groups of bacteria were < or = 1 mg/l. The activity of cefpirome against gram-negative bacteria is at least as good as that of aztreonam and imipenem. The only drug showing a better profile of activity than cefpirome is ciprofloxacin. The scattergram of the 513 isolates for cefpirome MICs and inhibitory zones with the 30 micrograms disc, showed that only eight isolates were not susceptible to cefpirome. These data suggest that the in vitro activity of cefpirome is comparable to if not better than that of other beta-lactams and tobramycin.
Bacteremia↗