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Biomedical subjects

M Younes

Publications and source records attributed to M Younes.

At least 253 records · Page 14Linked to original sources
PubMed1980

Phasic vagal influence on inspiratory motor output in anesthetized human subjects.

Vagal influence on inspiratory motor output was assessed in 20 normal subjects and in 12 patients with respiratory disorders under enflurane anethesia using the method of airway occlusion. The change in inspiratory duration during occlusion (delta TI) was measured from mechanical parameters (respiratory flow and tracheal pressure). In eight of the subjects, however, the effect of occlusion and augmentation of tidal volume was further evaluated from diaphragmatic electromyogram. In normal subjects delta TI (mechanical) averaged 0.15 s (range -0.1 to +0.77 s) and correlated with the duration of inspiration during occlusion. Electromyographic observations indicated that the change in neural TI exceeds the change in mechanical TI by approximately 0.2 s and that augmentation of tidal volume shortens TI with no apparent volume threshold. There was a tendency for vagal influence to be higher with restrictive lung disease and lower with obstructive airway disease. These observations indicate that a majority of humans display a significant vagal influence on TI in the spontaneous tidal volume range under anesthesia.

Aged↗
PubMed1980

The influence of silybin on the hepatotoxic and hypoglycemic effects of praseodymium and other lanthanides.

In rats, i.v. administration of praseodymium, cerium and lanthanum (3 to 14 mg/kg) produced a dose-dependent increase in the serum activities of GOT, GPT and SDH. These dose-response curves of serum enzyme activities were shifted to the right by simultaneous treatment with silybin (75 mg/kg i.p.). Silybin also attenuated the increase of bromosulphthaleine retention and prevented the accumulation of liver triglycerides induced by praseodymium (7 mg/kg i.v.). Furthermore, silybin reduced the mortality rate of rats treated with high doses of the lanthanides. Rats treated with praseodymium (7 mg/kg i.v.) developed a pronounced hypoglycemia. On the 3rd day after praseodymium injection liver glycogen decreased to 4%, liver glutathione (GSH) to 82%, hepatic microsomal cytochrome P-450 content to 53%, aniline hydroxylase activity to 58% and aminophenazone demethylase activity to 40% of the control values. Silybin prevented praseodymium-induced hypoglycemia completely and the changes in the biochemical parameters of liver function partially but did not influence the decrease of liver GSH.

Animals↗
PubMed1980

Lipid peroxidation as a consequence of glutathione depletion in rat and mouse liver.

Treatment of rats and mice with either vinylidene chloride or diethylmaleate led to a time-dependent depletion of liver glutathione (GSH). Incubations of liver homogenates from such glutathione-depleted animals resulted in a large increase of the spontaneous lipid peroxidation. This was suppressed by the hepatoprotective agents (+)-cyanidanol-3 and dithiocarb which may both act as antioxidants and radical scavengers while dithiocarb, in addition, inhibits the microsomal monooxygenase system. Addition of glutathione in a physiological concentration range totally inhibited lipid peroxidation. These findings are interpreted in terms of glutathione depletion leading per se to an increased lipid peroxidation, possibly due to its lack as part of the cellular defence system against endogenous toxic intermediates.

Animals↗
PubMed1979

Functional aspects of the superoxide dismutative action of Cu-penicillamine.

The superoxide dismutative action of Cu-penicillamine was examined by pulse radiolysis. The second order rate constand of the reaction wpith superoxide was 0.4 +/- o.2.10(9) M-1.s-1, comparable to the action of Fe and Mn-superoxide dismutases. No marked pH-dependence was seen. Neither ethylene diamine tetraacetic acid nor cyanide affected the catalytic action of Cu-penicillamine. The cyanide resistant reactivity as well as further X-ray photoelectron spectrometric measurements supported the suggestion of a Cu(I) stabilized sulphur radical being the active species involved in the catalysis of superoxide dismutation.

Binding Sites↗
PubMed1979

Effect of dithiocarb and dimethyl sulfoxide on irreversible binding of 14C-bromobenzene to rat liver microsomal protein.

The irreversible binding of [14C]-bromobenzene to rat liver microsomal protein in vitro was inhibited by dithiocarb and DMSO. Dithiocarb suppressed this binding in a time- and concentration-dependent manner (I50 = 4.5 10(-5) M). DMSO reduced the degree of covalent binding by 61% from 5 x 10(-5) M to 8 x 10(-4) M. Dithiocarb was also effective in inhibiting irreversible binding of bromobenzene to liver protein in vivo. Our results are consistent with the hypothesis that dithiocarb exerts its antihepatotoxic efficacy by depressing microsomal mixed-function oxidase activity.

Animals↗
PubMed1979

Effects of dithiocarb and (+)-cyanidanol-3 on the hepatotoxicity and metabolism of vinylidene chloride in rats.

The acute hepatotoxic effects of vinylidene chloride (VDC) were evidenced by measurement of the increase in the serum levels of the aminotransferase (GPT) and sorbitol dehydrogenase (SDH), hepatic glutathione (GSH) depletion and histological examinations in rats. The hepatoprotective agents dithiocarb and (+)-cyanidanol-3 proved well able to antagonize these toxic effects of VDC. While dithiocarb inhibited the in vivo metabolism of VDC in a closed exposure system, (+)-cyanidanol-3 had no influence at all. These findings substantiate the role of the microsomal monooxygenase system in the metabolism and hepatotoxicity of VDC. The mechanisms by which dithiocarb and (+)-cyanidanol-3 act as antihepatotoxic agents are different: the inhibition of the metabolic activation by dithiocarb and free radical-scavenging by (+)-cyanidanol-3.

Animals↗
PubMed1979

Studies on the mechanism of paracetamol-induced protection against paracetamol hepatotoxicity.

In rats, 3 days treatment with paracetamol (1 oral dose of 1 g/kg daily) produced a complete protection against the hepatotoxic actions of a further dose of paracetamol as documented by determination of serum enzyme activities (glutamic-oxaloacetic transaminase, (GOT), glutamic-pyruvic transaminase (GPT), sorbitol dehydrogenase (SDH), bromsulphthalein retention and histological investigations. Subacute paracetamol treatment decreased liver glutathione levels by 46%, liver microsomal cytochrome P-450 content by 23%, hepatic hydroxylation of aniline by 29% and hepatic demethylation of aminopyrine by 46%. It afforded also some protection against the hepatotoxic actions of carbon tetrachloride, bromobenzene and thioacetamide, but did not influence the antiphlogistic activity of paracetamol (carrageenan paw edema test). Plasma and liver concentrations of free paracetamol after oral administration of 1 g/kg paracetamol were somewhat higher in the subacutely paracetamol-pretreated rats than in the non-pretreated control animals whereas no differences in the concentrations of conjugated paracetamol were found between the 2 groups. Pretreatment with paracetamol did not influence the urinary excretion of free paracetamol but caused some shift in the urinary excretion of paracetamol conjugates: pretreated rats excreted 23% less of the paracetamol glucuronide and sulfate and 33% more of the paracetamol mercapturate than the control animals. A depression of the microsomal mixed-function oxidase activity is presumed to be the main cause of the paracetamol-induced protection against paracetamol hepatotoxicity.

Acetaminophen↗
PubMed1979

Models for metal-sulfur coordination in copper proteins.

The oxidation state of copper in several model compounds containing copper coordinated to sulfur, some of which are suggested model compounds for naturally occurring Cu-S chromophores, was determined employing x-ray photoelectron spectrometry. Copper was found to be present in a 3d10 state, which is characteristic for Cu(I). An initial photoreduction is excluded, as Cu(ethylenediamine)2 (SCN)2, in which a Cu-S bond is also present, was found to contain Cu(II) (3d9). As was the case with native parsley plastocyanin, the model compounds reacted effectively with superoxide anion radicals. We suggest that the electrons of the metal-sulfur chromophore in blue copper proteins are delocalized and that an equilibrium: RS--Cu(II) in equilibrium or formed from RS.Cu(I) exists.

Copper↗
PubMed1979

Steroid receptors in the canine epididymis.

High-affinity and low-capacity molecules that bind 5 alpha-dihydrotestosterone and oestradiol-17 beta have been demonstrated in the canine epididymis. The molecules were shown to be proteinaceous in nature, thermolabile and sedimented in a sucrose density gradient with a coefficient of 8S with respect to bovine serum albumin. Only minor differences were found for dissociation constants for oestradio-17 beta (3.5 +/- 1.74 S 10(-10) M) and 5 alpha-dihydrotestosterone (4.2 +/- 10.75 X 10(-10) M) (means +/- s.d.) in the three anatomically distinct regions of the epididymis.

Animals↗
PubMed1979

[Influence of 2-dimethylaminoethanol on the hepatotoxicity of paracetamol in rats and mice (author's transl)].

2-Dimethylaminoethanol (DMAE; 0.1--0.5 g/kg) significantly reduced the paracetamol-induced increments of serum-enzyme activities (GOT, GPT, SDH) in rats and mice. This hepatoprotective effect of DMAE depended on the applied dose in rats, but there was no complete protection following the highest dose. Paracetamol-induced depletion of hepatic glutathione (GSH) was not influenced by the simultaneous administration of DMAE in rats and mice. Metabolic disposition of paracetamol in the urine of rats showed an enhanced elimination of free paracetamol and the glucuronide in the DMAE-treated group, whereas the mercapturate excretion remained unchanged. Diminished p-hydroxylation of aniline in a 9000Xg supernatant of rat and mouse liver homogenates in the presence of DMAE indicated an inhibition of microsomal mixed-function oxidase activity, which is also involved in the metabolic activation of paracetamol.

Acetaminophen↗
PubMed1978

Involvement of superoxide in the catalytic cycle of diamine oxidase.

The reaction of pig kidney diamine oxidase (amine:oxygen oxidoreductase (deaminating) (pyridoxal-containing), EC 1.4.3.6) could be significantly inhibited by superoxide dismutase active copper chelates but not by native 2Cu,2Zn-superoxide dimutase (cuprein). The ligands alone as well as Cd2+, a heavy metal of similar toxicity to Cu2+, showed no inhibition whatsoever. This indicates that .O-2 participates in the catalytic cycle and is produced at a site scarcely accessible to such a large molecule as cuprein. A mechanism for the second, aerobic step of the diamine oxidase reaction is suggested.

Amine Oxidase (Copper-Containing)↗
PubMed1978

Reactivity of antiinflammatory and superoxide dismutase active Cu(II)-salicylates.

The activity of chelated Cu(II) with four different aspirin-like drugs in various superoxide dismutase assays was examined. Prior to these studies the oxidation state of the involved copper was measured by x-ray photoelectron spectrometry and was found to be +II throughout. All copper complexes were able to suppress the xanthine-xanthine oxidase mediated reduction of both cytochrome c and nitroblue tetrazolium as well as the formazan formation by KO2 in a specific manner. The hydroxylation of benzo-[alpha]-pyrene as well as the demethylation of 7-ethoxycoumarin using induced hepatic rat microsomes could be successfully inhibited by the employed Cu(II) chelates. Cu(II)-acetylsalicylate was the most active copper complex. Our findings support the proposal that Cu(II) chelates are the active forms of aspirin-like antiinflammatory agents.

Animals↗
PubMed1978

Effect of five human anesthetics on respiratory control in cats.

The effect of halothane, fentanyl, Innovar, thiopental, and ketamine on inspiratory output, vagal influence, and chest wall reflex was assessed in seven cats lightly anesthetized with pentobarbital, using the method of airway occlusion with and without rapid vagal cooling. All anesthetics depressed inspiratory output, as expressed by deltaP/deltat, of the first occluded inspiration. However, only halothane depressed peak inspiratory output (Pmax). Phasic vagal influence was markedly depressed by 2% halothane but was preserved under other anesthetics. The ability to induce tonic vagal influence (expiratory muscle recruitment) was lost under halothane. Inspiratory inhibitory chest wall reflex was evident in two cats during airway occlusion. Addition of any test anesthetic abolished the reflex. It is concluded that halothane should be avoided in studies dealing with assessment of vagal influence.

Anesthetics↗