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Biomedical subjects

M Roch

Publications and source records attributed to M Roch.

At least 37 records · Page 2Linked to original sources
PubMed1989

[Evaluation of the probability of the occurrence of pregnancy during oligo-astheno-teratospermia].

Analysis of several sperm counts makes possible the positive diagnosis of oligo-astheno-teratospermia. Attempts to determine their etiology and consequently their treatment, remain negative, in most cases. The physician involved must then try to answer the couple's concern about the prognosis. The prognosis depends on the alterations seen on the sperm count parameters; but there is no threshold figure under which no pregnancy is observed (except for zero), concerning the count, the gradual mobility or the morphology of the spermatozoids. Motility studies, survival tests in cervical secretions, in the female genital apparatus and in culture media or fertilization in vitro tests, improve the prognosis. However, an answer can only be provided if the fertility takes into account the age of the female partner and a study of her fertility as well as the duration of the infertility. Management will consist of a choice between discontinuation of the treatment, test of fertilization in vitro and temporizing, including trials of male treatment and treatment of possibly associated female factors.

Female↗
PubMed1989

Muscarinic actions and receptor binding of the enantiomers of BM 130, an alkylating analog of oxotremorine.

The enantiomers of the oxotremorine analog N-[4-(2-chloromethylpyrrolidine)-2-butynyl]-2-pyrrolidone (BM 130) were synthesized. The LD50 values of (+)- and (-)-BM 130 in mice (i.v.) were 10.4 +/- 1.4 and 13.5 +/- 1.9 mumol/kg, respectively. Atropine and N-methylatropine poorly protected against the lethal effects, suggesting that they were nonmuscarinic in nature. When administered i.v. to mice, (+)- and (-)-BM 130 were equipotent in producing peripheral and central muscarinic effects. ED50 values were 1.3 to 1.4, 2.8 to 3.2 and 0.20 to 0.26 mumol/kg, respectively, for salivation, tremor and analgesia (tail-flick assay). After i.p. injection, tremor was not observed and analgesic potency was reduced more than 10-fold compared to the i.v. route. The aziridinium ions [(+)- and (-)-BM 130A], formed by spontaneous cyclization of (+)- and (-)-BM 130, were virtually equipotent in eliciting contractions of the isolated guinea pig ileum and in causing salivation in mice. Their LD50 values in mice (i.v.) were 1.1 +/- 0.2 and 2.1 +/- 0.3 mumol/kg, respectively. The enantiomers of BM 130A had similar affinity for muscarinic receptors in the rat cerebral cortex as measured by competitive inhibition of (-)-[3H]N-methylscopolamine binding at 0 degrees C. The rate constants for alkylation of muscarinic receptors, obtained at 37 degrees C by measuring the decline in (-)-[3H]-3-quinuclidinyl benzilate binding to cortical homogenates that had been treated with various concentrations of (+)- and (-)-BM 130A for 20, 45 or 90 min, differed significantly for the two enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkylation↗
PubMed1988

Tertiary 3- and 4-haloalkylamine analogues of oxotremorine as prodrugs of potent muscarinic agonists.

A series of tertiary 3- and 4-haloalkylamines related to the muscarinic agent oxotremorine was synthesized. The compounds cyclized in neutral aqueous solution to quaternary ammonium salts, which, in contrast to the parent haloalkylamines, were potent muscarinic agonists in vitro. When administered systemically to mice, the haloalkylamines produced central (tremor and analgesia) and peripheral (salivation) muscarinic effects. Central potency was dependent on the rate of cyclization and on the route of administration. The N-methyl-N-(4-chlorobutyl)amine derivative 7 cyclized rapidly (t1/2 less than 0.4 min at 37 degrees C) and elicited tremor on iv but not on ip injection, whereas the N-methyl-N-(3-chloropropyl)amine 3 cyclized slowly (t1/2 = 436 min) and was not tremorogenic by either route of administration. The N-methyl-N-(3-bromopropyl)amine 4(t1/2 = 11 min) and its iodo analogue 5 (t1/2 = 14 min) were quite potent in eliciting central muscarinic effects on both iv and ip injection to mice. It is concluded that haloalkylamine analogues of oxotremorine may serve in vivo as prodrugs for potent quaternary ammonium salts and that they are capable of circumventing the blood-brain barrier to such salts.

Analgesia↗
PubMed1987

A model hypocholinergic syndrome produced by a false choline analog, N-aminodeanol.

N-aminodeanol is an analog of choline that serves as a less effective substrate in all of its known enzymatic and transport mechanisms. It was utilized to test the hypothesis that the selective vulnerability of cholinergic neurones in Alzheimer's disease is due to competition for the available choline between pathways for acetylcholine and phospholipid synthesis. Rats placed on a choline free diet containing an equivalent amount of N-aminodeanol develop a model hypocholinergic state comprising hyperreactivity, hyperalgesia, aggressive behavior and a deficit in learning and memory. These effects are associated with a progressive replacement of free and lipid-bound choline and acetylcholine with N-aminodeanol and its corresponding esters. Choline acetyltransferase is reduced in some brain regions, suggesting a loss of cholinergic neurones. We propose that this represents a potentially useful animal model of Alzheimer's disease which deserves further investigation.

Alzheimer Disease↗
PubMed1987

Regional differences in receptor reserve for analogs of oxotremorine in vivo: implications for development of selective muscarinic agonists.

The muscarinic actions of several analogs of oxotremorine were compared in the mouse. Compounds such as AKS 19 and BM 5 having low intrinsic efficacy (partial agonists) differentiated between centrally mediated muscarinic effects as they, like oxotremorine, were potent in producing analgesia and hypothermia but did not produce tremor. Instead they antagonized oxotremorine-induced tremor. They resembled oxotremorine in their ability to stimulate salivary secretion. Excellent correlations were found between the various muscarinic effects measured in vivo and spasmogenic activity on the guinea pig ileum and between tremorolytic potency and affinity for ileal muscarinic receptors. The results suggest that there are regional differences in the receptor reserve for muscarinic agonists that may affect in vivo responses to partial agonists in a qualitative manner. Responses to more efficacious agonists such as oxotremorine are affected only quantitatively by such differences. Efficacious agonists appeared to have a large receptor reserve with respect to salivation, analgesia and hypothermia, whereas their receptor reserve for the tremor response was lower. The possibility is raised of achieving selective muscarinic actions, even in the absence of distinct subtypes of muscarinic receptors, by exploiting regional differences in receptor density, in the efficiency of receptor-effector coupling and in endogenous levels of acetylcholine.

Analgesia↗
PubMed1985

Stereoselectivity of muscarinic receptors in vivo and in vitro for oxotremorine analogues. N-[4-(tertiary amino)-2-butynyl]-5-methyl-2-pyrrolidones.

The enantiomers of three 5-methyl-2-pyrrolidone analogues of the muscarinic agent oxotremorine (1) were synthesized. The pyrrolidine derivative (R)-13 was an antagonist to carbachol in the guinea pig ileum and also showed central and peripheral antimuscarinic activity in vivo. It was more potent and more selective than atropine in antagonizing the central effects of 1. The dimethylamino analogue (R)-14 and the trimethylammonium salt (R)-15 were potent agonists in the guinea pig ileum. (R)-14 showed both central muscarinic (hypothermia) and central antimuscarinic activity (antagonism of oxotremorine-induced tremor) in vivo. The R enantiomers of 13-15 were considerably more potent than the S enantiomers in vivo and in vitro irrespective of whether agonist or antagonist activity was measured. From a comparison of the contribution of the methyl group at the chiral center to the overall affinities, it is suggested that agonists and antagonists in this series bind in an essentially identical manner to the muscarinic receptor.

Abdominal Muscles↗
PubMed1985

Changes in presynaptic release of acetylcholine during development of tolerance to the anticholinesterase, DFP.

The rat myenteric plexus was used as a peripheral model for studying muscarinic modulation of acetylcholine (ACh) release from presynaptic muscarinic neurons during development of tolerance to the anticholinesterase agent, diisopropylfluorophosphate (DFP). DFP in arachis oil was administered subcutaneously to intact animals according to both acute and chronic regimens, with arachis oil injections serving as controls. Post-mortem analyses showed that the mean AChE activity level in whole brain was reduced under all DFP conditions to 18.0 +/- 1.4% when compared with the control level. After 10 days of DFP treatment, the AChE level was 22.3 +/- 2.1% of control in the myenteric plexus. There were no significant differences among the treatment groups in resting ACh release. Release evoked by electrical stimulation (difference between stimulated and resting release) in the absence of atropine, i.e., "basal rate," for strips taken at various times after a single injection of DFP did not differ from that for strips from animals receiving arachis oil only. However, basal release for strips from chronically treated subjects was significantly greater than that of controls (p less than 10(-3), although not different from each other. Analysis of variance (ANOVA) for repeated measures showed that there existed a highly significant atropine dependency in strips from all treatments when they were stimulated in concentrations of atropine from 10(-9) to 10(-5) M (p less than 10(-10). Further analyses established that the increases in rates of evoked ACh release as concentrations of atropine increased were similar for strips from chronically treated DFP and arachis oil animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1984

Hepatic metallothionein production and resistance to heavy metals by rainbow trout (Salmo gairdneri)--I. Exposed to an artificial mixture of zinc, copper and cadmium.

Rainbow trout developed elevated hepatic metallothionein concentrations after 4 weeks in a solution containing zinc, copper and cadmium in a fixed ratio of 400:20:1. Resistance to a combination of these metals increased in proportion to the concentration to which they were exposed for 4 weeks. The concentration of copper but not zinc or cadmium in the low molecular weight proteins separated by gel filtration was related to the concentrations of metallothionein present. The combined toxicity of the metals in the mixture was additive.

Adaptation, Physiological↗
PubMed1984

Hepatic metallothionein production and resistance to heavy metals by rainbow trout (Salmo gairdneri)--II. Held in a series of contaminated lakes.

Rainbow trout held in net pens for 4 weeks in three locations contaminated by heavy metals developed elevated levels of hepatic metallothionein but no acclimation to a combination of zinc, copper and cadmium. Toxicity of the mixture of zinc, copper and cadmium in a ratio of 400:20:1 increased with temperature in the range of 6-21 degrees C. Hepatic metallothionein concentrations after 4 weeks of exposure in situ was correlated with the degree of contamination as measured by zinc concentrations (P less than 0.01).

Adaptation, Physiological↗
PubMed1984

Chronic exposure of coho salmon to sublethal concentrations of copper--III. Kinetics of metabolism of metallothionein.

Juvenile coho salmon (Oncorhynchus kisutch) 3-8 g body weight were exposed to sublethal concentrations of copper acetate in water of hardness 280 mg/l (as CaCO3) using flow-through conditions. Concentrations of copper were approximately 1, 50, 100 or 150 micrograms Cu/l. Uptake of copper into blood, gills, kidney and liver was measured using 67Cu and into hepatic metallothionein. Chromatography on Sephadex G-75 was used to separate the protein from the cytosol. Copper was determined using atomic absorption spectrophotometry. The ratio of rates of uptake of copper and synthesis of metallothionein was consistent with published values for the copper content of copper-thionein, i.e. 7 to 1. After 4 weeks of continuous exposure the concentrations of copper and hepatic metallothionein levelled off at concentrations that were a function of the copper concentration in the water. After the plateau or steady-state had been reached, the rate of loss of metallothionein was measured by determining the change in specific-activity of isotope with time after incorporation of 35S-L-cysteine or 3H-L-lysine into the protein. The half-life for loss of metallothionein was a function of the exposure to copper, being about 13 days for control fish and 30 days for fish exposed to the greatest concentration of copper. Salmon that had been exposed to copper for 8 weeks neither gained hepatic metallothionein in a further 4 week exposure to copper, nor lost it when transferred for 4 weeks to clean water. Tolerance to copper exhibited by fish that continued to be exposed to it was partially lost after 4 weeks depuration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Hepatic metallothionein and resistance to copper in juvenile coho salmon.

1. Four groups of 600 juvenile coho salmon (Oncorhynchus kisutch) of 3-8g body weight were exposed to sublethal concentrations of copper acetate in water of hardness 280 mg/l (as CaCO3). 2. Flow-through conditions were maintained for a period of 10 weeks, during which the copper concentrations to which the groups of fish were exposed were approximately 1, 50, 100 and 150 micrograms Cu/l. 3. Hepatic metallothionein concentrations were measured using differential pulse polarography in filtrates of heat-denatured saline extracts of the tissues. 4. These values increased as a function of the copper concentration to maximum levels after 4 weeks of continuous exposure and thereafter remained more or less constant. 5. Flow-through 168 hr LC50 values for fish tested at intervals throughout the experiment increased to maximum values (2.5 X control values) at 1 week and during the next 3 weeks fell somewhat to stable but elevated values. 6. At 4 weeks, these were related to the metallothionein (MT) values by the regression equation 168 hr LC50 = 2.423 (+/- 0.455) X MT + 48.6 (+/- 31.1). 7. The probability that the relationship was not accidental exceeded 97%.

Animals↗
PubMed1982

Chronic exposure of coho salmon to sublethal concentrations of copper.--I. Effect on growth, on accumulation and distribution of copper, and on copper tolerance.

1. Coho salmon, exposed to sublethal levels of aqueous copper (1/4 and 1/2 LC50), lost appetite and ceased growing or showed decreased rates of growth. 2. Recovery of appetite and growth rate was faster in fish exposed to 1/4 of the LC50 than in those exposed to 1/2 of the LC50. 3. Copper levels were elevated in liver gill and kidney of exposed fish with the liver tissue accumulating a much larger amount of the metal than any other tissue. 4. The concentration of liver copper became constant at about the time that growth rate recovered. 5. The exposed fish exhibited much higher resistance to elevated aqueous copper levels than did the controls. 6. The results suggest that coho salmon may become acclimated to higher levels of copper and that acclimated fish are more tolerant to copper than control animals.

Animals↗
PubMed1982

Chronic exposure of coho salmon to sublethal concentrations of copper--II. Distribution of copper between high- and low-molecular-weight proteins in liver cytosol and the possible role of metallothionein in detoxification.

1. Liver cytosol samples from juvenile coho salmon exposed over a 14-week period to 70 micrograms/l (1/4 LC50) or 140 micrograms/l (1/2 LC50), were separated into high-molecular-weight and low-molecular-weight fractions by column chromatography on Sephadex G-75, and compared to similar samples obtained from control fish. 2. The levels of copper in the low-molecular-weight function of fish exposed to 70 micrograms/l were not significantly increased over control values for the first 6 weeks but then increased rapidly, while those of fish exposed to 140 micrograms/l increased substantially in the first 2-4 weeks of exposure, then levelled off. 3. In the exposed fish the levels of copper in the high-molecular-weight fraction were not significantly elevated above control levels over the first 8-10 weeks but then increased significantly. 4. The low-molecular-weight fractions of exposed fish were shown to contain increasing levels of metallothionein. The metallothionein was isolated on DEAE-cellulose and characterized by amino acid analyses.

Animals↗