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Biomedical subjects

M Salmona

Publications and source records attributed to M Salmona.

At least 199 records · Page 11Linked to original sources
PubMed1978

Intercalation with DNA is a prerequisite for daunomycin, adriamycin and its congeners in inhibiting DNAase I.

DNAase I from bovine pancreas is inhibited by Daunomycin, Adriamycin, Adriamycin-14-acetate and Adriamycin-14-octanoate, whereas it is not inhibited by N-trifluoroacetyladriamycin-14-valerate or N-trifluoroacetyl-adriamycin. The present study suggests that these inhibitors act not directly on the enzyme, but on DNA, forming stable complexes and thus interfering with enzyme activity. The correlation between DNA binding and enzyme inhibition is demonstrated by the fact that the compounds forming complexes with DNA inhibit DNAase I activity, whereas those which do not form complexes with DNA cause no inhibition.

DNA↗
PubMed1978

The absorption by human volunteers of glutamic acid from monosodium glutamate and from a partial enzymic hydrolysate of casein.

Peripheral plasma concentrations of glutamic and aspartic acids and alanine were measured after ingestion of monosodium glutamate or a pancreatic hydrolysate of casein by human volunteers. The doses of each material were such that they contained similar amounts of glutamic acid. Plasma glutamic acid concentrations rose promptly after the monosodium glutamate but mean peak concentrations were well below those likely to cause neurological damage. Plasma aspartic acid concentrations also rose after the monosodium glutamate but the behaviour of plasma alanine concentrations suggested that intestinal transamination of glutamic acid was insufficient to cause an appreciable rise in alanine concentration in the peripheral plasma. Significant increments in plasma glutamic acid concentrations did not occur after the pancreatic hydrolysate of casein and it is probable that competition for absorptive mechanisms by other amino acids, both free and peptide-bound, causes absorption of glutamic acid to be slower from mixtures of peptides and amino acids than from monosodium glutamate itself.

Absorption↗
PubMed1978

Arene oxides in styrene metabolism, a new perspective in styrene toxicity?

The metabolism of styrene was studied in the rat after intraperitoneal administration of the cold and the 14C-labeled compound. In addition to phenylethylene glycol, mandelic acid, benzoic acid and hippuric acid, phenolic metabolites, namely, 4-vinylphenol, p-hydroxymandelic acid, p-hydroxybenzoic acid, and p-hydroxyhippuric acid, were identified in the urine of the treated animals. These biotransformation products were characterized by mass spectrometry and by comparative thin layer chromatography with standard compounds. Results of covalent binding studies of 14C-phenylethylene glycol to rat liver microsomal proteins suggest that these phenolic compounds may be formed as a result of chemical rearrangements of unstable arene oxides, reactive intermediates possibly implicated in styrene toxicity.

Animals↗
PubMed1976

A specific gas chromatographic method for the determination of microsomal styrene monooxygenase and styrene epoxide hydratase activities.

A gas chromatographic (GC) method for the determination of the metabolite resulting from the activities of microsomal styrene monooxygenase (epoxide synthetase) and epoxide hydratase using styrene or styrene epoxide as substrates has been developed. The determination of the activities of both enzymes is based on the GC determination of phenylethylene glycol after its esterification with n-butylboronic acid. Kinetic parameters for both enzymes are given.

Animals↗
PubMed1976

Uptake of 14C-5-hydroxytryptamine by human and rat platelets and its pharmacological inhibition. A comparative kinetic analysis.

In order to approach the uptake of 14C-5HT by platelets as a first-order process, experimental conditions were selected in which accumulation of the amine either by diffusion or by other passive nonsaturable processes could be excluded. These conditions included an incubation period of 14C-5HT with human or rat platelets of 4 min or 30 s, respectively and the use of substrate concentrations around the calculated apparent Km values (0.25 - 2.0 muM). While the apparent Km values were rather similar for human and rat platelets, Vmax was about 5 times higher in rat than in human platelets. The kinetic model adopted in this study was used to evaluate the relative potency and the type of inhibiton of 14C-5HT uptake exhibited by imipramine, chlorimipramine and (+)-fenfluramine. All 3 compounds inhibited 14C-5HT uptake by platelets. Chlorimipramine was about 10 times more effective than imipramine both in rat and in human platelets. Both drugs were more potent inhibitors on human than on rat platelets. (+)-Fenfluramine was almost as active as imipramine on rat but 30 times less potent than imipramine on human platelets. Both imipramine and chlorimipramine inhibited 14C-5HT uptake by an apparent non-competitive mechanism, whereas (+)-fenfluramine appeared to act as a competitive inhibitor. No differences were found in this respect between human and rat platelets. Pharmacological or therapeutic doses of these drugs usually result in plasma concentrations similar to those found in this study to effectively inhibit platelet 14C-5HT uptake.

Adult↗
PubMed1976

Microsomal styrene mono-oxygenase and styrene epoxide hydrase activities in rats.

1. Styrene epoxide formation and styrene epoxide hydration have been studied in liver, lung, kidney, heart, spleen and brain of female and male rats. 2. Styrene epoxide formation is NADPH-dependent although it is enhanced when NADH is added together with NADP. This enzymic activity is inhibited by metyrapone and SKF 525-A but not by the effective inhibitors of epoxide hydrase, 1,2-epoxy-3,3,3-trichloropropene and cyclohexene oxide. 3. Known inducers of liver microsomal mono-oxygenases show a different activity on the two enzymes. Phenobarbital increases both formation and hydration of styrene epoxide; and carbamazepine increase the hydration but not the formation of styrene epoxide; a steroid contraceptive combination (lynestrenol+ mestranol) increases styrene epoxide formation while it inhibits epoxide hydrase; 3-methylcholanthrene does not affect either of the activities.

Animals↗
PubMed1976

Activity of liver microsomal mono-oxygenases on some epoxide-forming cyclic tricyclic drugs. I. Kinetics in vitro.

1. The mono-oxygenase activity that forms epoxides has been studied in rat liver microsomes using as substrates carbamazepine and cyclobenzaprine, tricyclic drugs which form stable epoxides in vivo and in vitro. 2. A simple gas chromatographic method has been used to determine the amount of epoxide formed and the linearity of the enzymic reaction with time and protein concentration has been demonstrated. 3. Pre-treatment with carbamazepine increases the rate of formation of carbamazepine epoxide in rat liver microsomal preparations. 4. The effect of SKF 525-A on the formation of these epoxides has been studied.

Animals↗
PubMed1975

Gas chromatographic-mass spectrometric determination of intact C3-hydroxylated benzodiazepine glucoronides in urine.

A method is described for the determination C3-hydroxylated benzodiazepine glucuronides in biological samples. Oxazepam and lorazepam glucuronides are measured as methyl esters and trimethylsilyl derivates by a gas chromatographic procedure. The applicability of the method has been tested on the urine of rats, guinea pigs, rabbits and man, receiving oxazepam orally. Oxazepam glucuronide was not found in rat urine but it was present in the urine of rabbits (5.7% of the administered dose), guinea pigs (9.5%) and man (13.4-26.9%).

Administration, Oral↗
PubMed1975

Relationship of in vitro hydrolysis of 17-chloroacetylajmaline and 17-acetylajmaline in different animal species.

17-Chloroacetylajmaline and 17-acetylajmaline are reported to have in vivo antiarrhythmic activity and are metabolized by hydrolysis. Since the hydrolysis product, ajmaline, may be the actual antiarrhythmic agent, the hydrolysis of these derivatives by various tissues of the guinea pig, rat, and mouse was determined in vitro by a titrimetric method and compared to hydrolysis by alpha-naphthylacetate. The heart is the most active tissue in the guinea pig for hydrolyzing 17-chloroacetylajmaline. The hydrolyzing activity is greater in the guinea pig than in rat or mouse heart, corresponding with the more significant pharmacological activity in the guinea pig. 17-Chloroacetylajmaline has a significantly lower Km value than 17-acetylajmaline, which is in agreement with the in vivo activity.

Ajmaline↗
PubMedDate not supplied

Apoptosis-mediated neurotoxicity induced by beta-amyloid and PrP fragments.

The neurotoxic activity of beta-amyloid (beta A) and prion protein (PrP) fragments contributed to the hypothesis concerning a causal role of amyloid deposits in Alzheimer disease (AD) and in prion-related encephalopathies. In this study, we investigated some aspects of the molecular mechanisms associated with neurotoxic activity of synthetic peptides homologous to beta A (beta 25-35) or PrP (PrP106-126) fragments. Chronic (5-7 d) exposure to both peptides induced neuronal death by apoptosis, as suggested by biochemical and morphological analysis. The apoptotic mechanism was confirmed by ultrastructural examination. The intracellular cascade of events activated by peptides was investigated by Northern blot and PCR analysis of expression of early genes (c-fos, c-jun, c-myc) and other proteins (p53, SGP-2 bcl-2, HSP70, Ich-1) potentially involved in apoptosis. With the exception of bcl-2 mRNA decrease and a slight increase of SGP-2 in PrP106-126-treated cells, no consistent alterations of these mRNA expressions were found in neuronal cells exposed to beta 25-35 or PrP106-126. Furthermore, we synthesized amidated homologs of both peptides with low amyloidogenic activity to test directly the relationship between amyloid fibrils and cell death. The neurotoxicity exhibited by PrP106-126-NH2 was similar to that observed with original peptide, whereas the amidation of beta 25-35 partially reduced the neurotoxicity of this peptide.

Alzheimer Disease↗
PubMedDate not supplied

Structure reactivity relationships in the microsomal oxidation of tertiary amines.

Apparent kinetic parameters Vmax and KM have been measured for the oxidative N-demethylation of twelve para-substituted N, N-dimethylanilines catalysed by rat liver microsomes. Vmax was enhanced by pretreatment of the rats with phenobarbital, whereas pretreatment with beta-naphthoflavone gave no appreciable enhancement. In the case of phenobarbital pretreatment the kinetic parameters could be expressed in terms of lipophilic and electronic effect of the substituents. Kinetic parameters from control and beta-naphthoflavone microsomes gave no statistically meaningful correlation.

Amines↗