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Biomedical subjects

M Younes

Publications and source records attributed to M Younes.

At least 199 records · Page 11Linked to original sources
PubMed1985

The role of iron in the paracetamol- and CCl4-induced lipid peroxidation and hepatotoxicity.

Treatment of non-induced or phenobarbital-induced, glutathione-depleted mice with 400 mg/kg paracetamol led to a marked ethane exhalation as an index of in vivo lipid peroxidation (LPO) and to a significant elevation of liver-specific serum enzyme activities. Similar effects were seen with rats treated with 0.5 ml/kg CCl4. Pretreatment with the iron-chelating agent desferrioxamine (DFO) clearly suppressed lipid peroxidation in all cases, but inhibited only the CCl4-induced hepatotoxicity. Treatment of mice with desferrioxamine alone showed no hepatotoxicity at all, nor did it influence liver GSH-levels. In addition, DFO had no effect on hepatic microsomal enzyme activities responsible for the bioactivation of both paracetamol and CCl4. These findings are consistent with the theories which indicate that lipid peroxidation requires the presence of Fe2+-ions, regardless of the initiating agent, and that LPO is involved in CCl4-toxicity, but most probably not in paracetamol-induced liver damage. Furthermore, Fe2+-ions might play a role as mediators of CCl4-hepatotoxicity.

Acetaminophen↗
PubMed1985

Fe2+-supported in vivo lipid peroxidation induced by compounds undergoing redox cycling.

Treatment of male mice with the redox cycling compounds nitrofurantoin, paraquat, diquat or menadione failed to elicit in vivo lipid peroxidation as evidenced by ethane exhalation. The first three led to an enhanced ethane production, however, when the animals were pretreated with a low dose of Fe2+. While GSH-depletion by phorone pretreatment alone had no influence on the in vivo lipid peroxidation as evidenced by ethane expiration in the presence of either compound, the combined treatment with phorone, Fe2+ and nitrofurantoin, paraquat or diquat led to a further enhancement of ethane exhalation. These results indicate that redox cycling compounds do not initiate lipid peroxidation by themselves, but are well capable of stimulating the iron-induced LPO.

Animals↗
PubMed1985

Effect of hypoxia on the metabolism and hepatotoxicity of carbon tetrachloride and vinylidene chloride in rats.

The metabolism of vinylidene chloride (VDC) and carbon tetrachloride (CCl4) was investigated by measuring the removal of the compounds from the atmosphere of a closed exposure system occupied with male rats. Hepatotoxicity was evidenced in the same rats by determining serum enzyme activities of the aminotransferases (GOT, GPT) and sorbitol dehydrogenase (SDH) before, at the end of the exposure time and 24 hrs later. Control rats exposed to VDC concentrations up to 2000 p.p.m. showed only slight increases of serum aminotransferase- and SDH-activities, which were not at all observed under hypoxic conditions. Hypoxia evoked a small, but significant reduction of the VDC metabolism at 500 p.p.m., but not at 2000 p.p.m. exposure concentration. In contrast to VDC CCl4-metabolism (150 p.p.m.) was increased under hypoxia and consequently hepatotoxicity was aggravated.

Animals↗
PubMed1985

Studies on the oxygen radical mechanism involved in the small intestinal reperfusion damage.

Characteristic mucosal lesions develop in the small intestine during ischaemia and hypotension. This tissue damage can be further aggravated in the immediate reperfusion phase, presumably secondary to the generation of oxygen free radicals which have been proposed to be generated in this situation through the hypoxanthine-xanthine oxidase system. This was further investigated in the cat small intestine using a standardized regional intestinal hypotension model in which the effects of allopurinol (a xanthine oxidase inhibitor) were compared to those of an exogenous supply of inosine. The grade of mucosal damage, the nucleotide levels, the concentrations of hypoxanthine, total and oxidized glutathione, and of conjugated dienes were measured in the intestinal tissue. The results indicate that oxygen radicals generated by xanthine oxidase are very important, but not the only significant factor in the small intestinal reperfusion damage.

Adenosine Diphosphate↗
PubMed1985

Breathing pattern during and after exercise of different intensities.

We recently observed rapid shallow breathing during recovery from maximal exercise in some normal subjects. We wondered whether this phenomenon is randomly related to level of exercise or is limited to recovery from very high levels of exercise. We monitored ventilation, tidal volume, and respiratory frequency in seven normal subjects during and after exercise. Each subject exercised on several occasions on separate days. At least two of the tests were maximal (i.e., subject terminated). In the other tests exercise was terminated by the experimenter at different fractions of the highest level attained by the subject. There was no systematic difference between breathing pattern during exercise and recovery in tests where final O2 consumption (VO2) was 45-92% of the subjects' highest VO2. By contrast 13 of 19 studies in which final VO2 was 92-100% of highest VO2 were followed by relative rapid shallow breathing. We conclude that rapid shallow breathing during recovery from exercise is a phenomenon that is limited to very high exercise levels. On consideration of the various mechanisms that may be entertained to explain this phenomenon, we believe that development of pulmonary congestion-interstitial edema at very high levels of exercise is the most consistent with our findings.

Adult↗
PubMed1985

Central adaptation to inspiratory-inhibiting expiratory-prolonging vagal input.

We reported earlier on the changes in excitability of central respiratory switching mechanisms in the course of a brief inspiratory-inhibiting vagal stimulus (J. Appl. Physiol. 50: 1183-1192, 1981). To further define the dynamics of central processing of such input we studied the changes in the excitability of timing mechanisms in the immediate (less than 1.0 s) and late (1-20 s) periods after stimulus removal. We also examined the changes in respiratory timing in the course of protracted (greater than 20 s) stimulation. Studies were done using pentobarbital-anesthetized cats. For studies involving long-term stimulation or late off responses, cats were paralyzed, vagotomized, carotid denervated, and artificially ventilated. We found that the inspiratory inhibitory influence of a brief stimulus continues, in a declining fashion, for 0.3-10 s after removal of the stimulus. This was followed by a paradoxical response, inspirations were prolonged and expirations were shortened, which was maximal 1-2 s after stimulus removal and which declined gradually over a period of 6-16 s. There was progressive decline in inspiratory-shortening expiratory-prolonging influence in the course of sustained stimuli. These results indicate substantial adaptation in the course of even brief stimuli and provide an explanation for inspiratory-expiratory duration and expiratory-inspiratory duration linkages.

Action Potentials↗
PubMed1985

Effect of inspiratory muscle fatigue on breathing pattern.

Our aim was to determine whether inspiratory muscle fatigue changes breathing pattern and whether any changes seen occur before mechanical fatigue develops. Nine normal subjects breathed through a variable inspiratory resistance with a predetermined mouth pressure (Pm) during inspiration and a fixed ratio of inspiratory time to total breath duration. Breathing pattern after resistive breathing (recovery breathing pattern) was compared with breathing pattern at rest and during CO2 rebreathing (control breathing pattern) for each subject. Relative rapid shallow breathing was seen after mechanical fatigue and also in experiments with electromyogram evidence of diaphragmatic fatigue where Pm was maintained at the predetermined level during the period of resistive breathing. In contrast there was no significant difference between recovery and control breathing patterns when neither mechanical nor electromyogram fatigue was seen. It is suggested that breathing pattern after inspiratory muscle fatigue changes in order to minimize respiratory sensation.

Adult↗
PubMed1985

Biliary excretion of acetaminophen in diabetic and hyperthyroid rats.

In streptozotocin-induced diabetic rats the biliary excretion of total acetaminophen (AA) was reduced to 14.1% of the dose (100 mg/kg i.v.) as compared to 24.6% in controls. This was due to a significant decrease in the amounts of AA-sulfate and AA-glucuronide, whereas the AA-GSH excretion was not altered. These effects were paralleled by a marked decrease in the bile flow in diabetic rats. In hyperthyroid rats (pretreated with 0.1 mg/kg T3 for 4 days) no significant alterations in the total AA or AA-conjugate excretion into bile were observed; moreover bile flow in hyperthyroid rats was in the same range as for controls. In all, known changes in hepatic microsomal or cytosolic enzyme and cosubstrate concentrations during the diabetic or hyperthyroid state do not at all correlate with their influence on the biliary excretion of AA and its conjugates.

Acetaminophen↗
PubMed1984

Glutathione and GSH-dependent enzymes in the human gastric mucosa.

The gamma-glutamyl-transferase activity, the total glutathione content, the GSH-peroxidase activity, and the GSH S-transferase activity using an aryl substrate were estimated in the S9 fraction of gastric biopsy specimens taken from patients with normal stomach morphology (n = 24), acute gastritis (n = 15), chronic-atrophic gastritis (n = 10), gastric ulcer (n = 9), and carcinoma of the stomach (n = 12). The total glutathione content of normal gastric mucosal specimens was significantly higher than that of human liver biopsy specimens, whereas the GSH-peroxidase and the GSH S-aryltransferase activities were much lower than those found in the liver. Specimens of gastric ulcer had significantly lower enzyme activities of GSH-peroxidase and GSH-aryltransferase, whereas gastric cancer tissue had significantly lower concentrations of total glutathione. The intraindividual comparison of tumorous and non-tumorous tissue showed a consistent decrease of total glutathione as well as of GSH-aryltransferase activity in carcinomatous tissue.

Adenocarcinoma↗
PubMed1984

Glutathione and GSH-dependent enzymes in the tumorous and nontumorous mucosa of the human colon and rectum.

A high content of total glutathione and high activities of both GSH S-aryltransferase (CDNB) and GSH peroxidase were found in different segments of the human intestinal mucosa comparable to findings in human gastric mucosa. Intraindividual comparisons of tumorous and nontumorous tissue specimens in patients with adenocarcinomas of the colon and rectum revealed no marked differences in their glutathione content and enzyme activities except in the sigma, where we found significantly lower GSH concentrations and higher GSH S-aryltransferase activities in the carcinomatous tissue. gamma-Glutamyl-transpeptidase activity, a marker of neoplastic cell growth in experimental hepatocarcinogenesis, did not differ between tumorous and nontumorous tissue areas. The presence and high activity of the GSH-dependent enzyme system in different segments of the human intestinal mucosa may reflect its role in the defense against toxic and putative carcinogenic xenobiotics entering the body via the gastrointestinal tract.

Adenocarcinoma↗
PubMed1984

Oxidative tissue damage following regional intestinal ischemia and reperfusion in the cat.

Regional intestinal ischemia in cats resulted in an accumulation of hypoxanthine within 2 h, the concentration of which rose from 0.062 to 1.131 nmol/mg protein. A similar rise in AMP content (from 0.5 to 3.2 nmol/mg protein) was observed, but not in the ADP level. In parallel, ATP content decreased from 7.5 to 2.8 nmol/mg protein. Reperfusion of the ischemic tissue was followed by rapid metabolism of the purine metabolites; after 1 h of reperfusion the tissue level of hypoxanthine was 0.186 nmol/mg protein, of AMP 0.7 nmol/mg protein, and of ATP 4.3 nmol/mg protein. The oxidation of hypoxanthine, mediated by xanthine oxidase, is accompanied by the release of superoxide ions. Consequently, the concentration of oxidized glutathione was doubled upon reperfusion, while marked lipid peroxidation took place, as evidenced by the rise in conjugated diene content from 2.8 mumol/g tissue before reperfusion to 5.6 mumol/g tissue after 10 min of reoxygenation. In line with these findings is the fact that histologically observable damage occurred mainly in the presence of oxygen. These data indicate that, at least in our model, rapid reoxygenation is a major cause of "ischemic" tissue damage.

Adenine Nucleotides↗
PubMed1984

Sex differences in the susceptibility of rats to carbon tetrachloride--alcohol-induced liver injury.

Treatment of male and female rats with carbon tetrachloride (CCl4, twice weekly, 0.2 ml/kg p.o.) and a 5% alcohol solution during four weeks evoked strong increments of the serum enzyme activities of the aminotransferases (GOT, GPT) and the sorbitol dehydrogenase (SDH). These occurred earlier and were more pronounced in male compared to female rats. Hepatic triglyceride contents as a measure of fatty infiltration was augmented three-fold both in males and females at the end of the experiment. Hepatic hydroxyproline contents were enhanced seven-fold in males, but only two-fold in females. It is concluded that female rats are less susceptible to CCl4--alcohol-induced liver damage, especially hydroxyproline accumulation, which is explained by the known fact that females are more resistant against CCL4-hepatotoxicity as a consequence of a minor role of bioactivation in the metabolic degradation of CCL4 by females.

Alanine Transaminase↗
PubMed1984

Aldrin epoxidase and dimethylhydrazine demethylase activities in tumorous and non-tumorous tissue of the human colon and rectum.

High activities of aldrin epoxidase and dimethylhydrazine demethylase were found in human colon and rectum mucosa, the first being as high as in human liver biopsy specimens. Comparisons between tumorous (adenocarcinomas) and non-tumorous tissues of the same individuals revealed loss of activities in tumorous specimens. The presence of epoxidizing enzymes and demethylation of the organ-specific colon carcinogen dimethylhydrazine (DMH) in the intestinal muscosa of tumor-bearing patients implicate them with chemical carcinogenesis also in humans.

Adenocarcinoma↗
PubMed1984

The role of iron in the NADPH-dependent lipid peroxidation due to glutathione depletion by phorone.

Enhanced NADPH-dependent LPO in rat liver postmitochondrial supernatants in vitro due to depletion of GSH by treatment with phorone (diisopropylidene acetone) in vivo was inhibited by Fe2+-chelating agents (desferrioxamine, DETAPAC), but not by scavengers of .O2-, H2O2, singlet oxygen or .OH-radicals, indicating that a perferryl ion (Fe2+ . O2) is needed as an initiating factor. In vivo, rats treated with phorone (250 mg/kg i.p.) exhaled 1.4 times as much ethane within 4 h as compared to controls. Pretreatment with FeSO4 resulted in a 6.9-fold enhancement of LPO as compared to Fe2+-pretreated controls. Our results indicate that GSH-depletion results in a strong enhancement of NADPH-dependent LPO also in vivo, provided that an initiating factor is present.

Animals↗
PubMed1984

Relation between respiratory neural output and tidal volume.

We recently described a model for the relation between respiratory neural and mechanical outputs (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 51: 963-1001, 1981). In this communication we utilize the model to address the following questions. 1) How sensitive is tidal volume (VT) to shape and timing of respiratory neural output (N)? 2) How effective are shape and timing characteristics of N in load compensation? 3) For a given VT, what is the most economical shape and timing of N? Using different values of passive respiratory mechanics, we generated the VT profiles associated with theoretical N waveforms having different shape and timing parameters. We found that 1) with normal mechanics VT is moderately sensitive to inspiratory time (TI) but not to shape of N, whereas with high resistance and short TI, VT is very sensitive to shape and timing; 2) changes in shape, within the physiological range, can serve as potent load-compensatory mechanisms; and 3) for a given VT, the most economical (lowest mean pressure) N pattern is one with a very short TI and a rising phase that is convex to time axis. This holds true even with high resistance.

Lung Volume Measurements↗
PubMed1984

Respiratory mechanics and breathing pattern during and following maximal exercise.

We looked for evidence of changes in lung elastic recoil and of inspiratory muscle fatigue at maximal exercise in seven normal subjects. Esophageal pressure, flow, and volume were measured during spontaneous breathing at increasing levels of cycle exercise to maximum. Total lung capacity (TLC) was determined at rest and immediately before exercise termination using a N2-washout technique. Maximal inspiratory pressure and inspiratory capacity were measured at 1-min intervals. The time course of instantaneous dynamic pressure of respiratory muscles (Pmus) was calculated for the spontaneous breaths immediately preceding exercise termination. TLC volume and lung elastic recoil at TLC were the same at the end of exercise as at rest. Maximum static inspiratory pressures at exercise termination were not reduced. However, mean Pmus of spontaneous breaths at end exercise exceeded 15% of maximum inspiratory pressure in five of the subjects. We conclude that lung elastic recoil is unchanged even at maximal exercise and that, while inspiratory muscles operate within a potentially fatiguing range, the high levels of ventilation observed during maximal exercise are not maintained for a sufficient time to result in mechanical fatigue.

Adult↗