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Biomedical subjects

P Granger

Publications and source records attributed to P Granger.

At least 19 recordsLinked to original sources
PubMed1995

Modulation of the gamma-aminobutyric acid type A receptor by the antiepileptic drugs carbamazepine and phenytoin.

We report here that carbamazepine and phenytoin, two widely used antiepileptic drugs, potentiate gamma-aminobutyric acid (GABA)-induced Cl- currents in human embryonic kidney cells transiently expressing the alpha 1 beta 2 gamma 2 subtype of the GABAA receptor and in cultured rat cortical neurons. In cortical neuron recordings, the current induced by 1 microM GABA was enhanced by carbamazepine and phenytoin with EC50 values of 24.5 nM and 19.6 nM and maximal potentiations of 45.6% and 90%, respectively. The potentiation by these compounds was dependent upon the concentration of GABA, suggesting an allosteric modulation of the receptor, but was not antagonized by the benzodiazepine (omega) modulatory site antagonist flumazenil. Carbamazepine and phenytoin did not modify GABA-induced currents in human embryonic kidney cells transiently expressing binary alpha 1 beta 2 recombinant GABAA receptors. The alpha 1 beta 2 recombinant is known to possess functional barbiturate, steroid, and picrotoxin sites, indicating that these sites are not involved in the modulatory effects of carbamazepine and phenytoin. When tested in cells containing recombinant alpha 1 beta 2 gamma 2, alpha 3 beta 2 gamma 2, or alpha 5 beta 2 gamma 2 GABAA receptors, carbamazepine and phenytoin potentiated the GABA-induced current only in those cells expressing the alpha 1 beta 2 gamma 2 receptor subtype. This indicates that the nature of the alpha subunit isoform plays a critical role in determining the carbamazepine/phenytoin pharmacophore. Our results therefore illustrate the existence of one or more new allosteric regulatory sites for carbamazepine and phenytoin on the GABAA receptor. These sites could be implicated in the known anticonvulsant properties of these drugs and thus may offer new targets in the search for novel antiepileptic drugs.

Animals↗
PubMed1994

The NMDA receptor antagonist eliprodil (SL 82.0715) blocks voltage-operated Ca2+ channels in rat cultured cortical neurons.

The effect of the non-competitive NMDA receptor antagonist eliprodil on NMDA receptor- and voltage-operated Ca2+ currents was investigated in rat cultured cortical neurons by using the whole-cell patch clamp technique. With neurons voltage-clamped at -40 mV, eliprodil reduced in a concentration-dependent manner the inward current induced by N-methyl-D-aspartate (NMDA) (10 microM) in the presence of D-serine with an IC50 of 0.67 microM (Imax = 83%). Eliprodil also blocked the total inward Ba2+ current carried in part by L- and N-type Ca2+ channels with an IC50 of 1.48 microM (Imax = 87%). These results suggest that the neuroprotective properties of eliprodil could be due to its combined ability to antagonize the NMDA receptor- and voltage-operated Ca2+ channels.

Animals↗
PubMed1994

A 13C solid-state NMR study of the structure and auto-oxidation process of natural and synthetic melanins.

This paper presents a 13C CP/MAS NMR study of the melanin pigments obtained through natural and synthetic origins: sepia-melanin from squid ink and three synthetic 5,6-dihydroxyindole-melanins prepared using different non-enzymatic oxidation pathways. The synthetic pigments can be distinguished from natural melanin by the absence of aliphatic carbons, thereby confirming the unreacted 3,4-dihydroxyphenylalanine and the proteinaceous origins of the aliphatic resonances in natural eumelanin. The spectra of selected non-protonated carbon resonances and those with only protonated carbon signals led to a quantitative analysis. An auto-oxidative experiment using a synthetic melanin, over a period of 130 h, has shown an unusually slow disappearance of hydrogen peroxide formed in situ. The 13C-NMR spectrum of the insoluble oxidized synthetic melanin compared to that before auto-oxidation clearly demonstrates that the oxidation process is associated with chemical changes within the pigment; i.e., carbonyl functional group formation and an increase of the non-protonated carbons fraction.

Animals↗
PubMed1993

Evaluation of the stability and quality of sleep using Hjorth's descriptors.

Hjorth's descriptors (NSD) (activity, mobility, and complexity) provide a useful tool for evaluating micro- and macrostructural elements of sleep. In rats, the automatic analysis of sleep recordings by means of NSD calculated from SM and Vis derivations allow different sleep stages to be discriminated. Activity distribution over the total recording permits the definition of a global effect on the EEG. Moreover, the quality of sleep can be evaluated by the variations of the SM activity distribution by considering different classes of amplitude. Index and rate of unstable amplitude segments (UAS) constitute useful parameters to analyse the stability and quality of sleep with different models of insomnia and after pharmacological treatment. The UAS in rats can be compared to CAPs in humans. The NSD are also able to define quality and stability of human sleep. EEG analysis using NSD provides a novel perspective for the analysis of the stability and quality of rat and human sleep. This microstructural analysis of sleep appears to be a useful tool for pharmaco-EEG studies.

Animals↗
PubMed1991

[Malignant degeneration on ileostomy for rectocolonic polyposis].

One case of malignant degeneration on an ileostomy following proctocolectomy for familial intestinal polyposis is reported. On the basis of a review of the literature, the nosological context of this disease, the etiopathogenesis of cancerization and the surgical consequences are determined.

Adenocarcinoma↗
PubMed1991

[Multiorgan procurement (MPO). Who? How? What results?].

Between 1985 and 1988, 156 organs were harvested using a multiorgan procurement technique (MPO) in the Urology Dept of Grenoble University Hospital (50 MOP). All the organs transplanted either in Grenoble or in other centers have been followed up after transplantation to try to appreciate their value and function. The surgical procedure is described, and results, organ by organ, are given. The conclusion is that the MOP technique is perfectly usable and reliable without jeopardizing any of the transplanted organs.

Adolescent↗
PubMed1990

[The repair of recurrent postoperative incisional hernias. Objectives and therapeutic indications (68 cases)].

Among 327 surgical repairs of incisional hernias done between 1974 and 1989, 68 repairs (21%) were performed because of a primary treatment failure. Failed primary attempts of cure had been unique in 71%, and multiple in 29% of cases; their procedure had been essentially suture or herniorrhaphy. Site of recurrent incisional hernia (R.I.H.), was midline or lateral incision in respectively 84% and 16% of cases. Size of R.I.H. was considered as large in two third of cases. Operation was performed electively in majority of cases (93%). More than half of the patients were "prepared" by preoperative pneumoperitoneum and/or weight reducing regimen. Mersilene* mesh was used in 81% of cases. Results of treatment of R.I.H. are reported, depending on procedure. Among 55 cures by use of Mersilene* mesh, 1 patient died (from myocardial infarction), and 5 recurrences occurred, 4 of which from sepsis. Study of complications and failures suggests: 1) careful attention to indications, 2) advantages of a large size Mersilene* mesh, 3) attention to preoperative treatment, especially weight loss regimen and progressive pneumoperitoneum.

Adult↗
PubMed1988

Aspects of sleep-wakefulness architecture by computer analysis in cats.

In the present study, using an automatic method to discriminate the stages of sleep-wakefulness, 180 control recordings on 15 chronically implanted cats were examined. In addition to a quantitative analysis, some aspects of the sleep-wakefulness architecture were considered, especially the nature and the distribution of the sleep phases that lead to paradoxical sleep (normal sequences) or to wakefulness (abortive sequences). Taken together, these features allow the definition of a 'control profile' which could be useful for the better characterization of drug effects.

Animals↗
PubMed1986

Hypnotics: clinical value of pharmaco-EEG methods.

The central effects of sedative-hypnotic drugs were defined through the use of electroencephalographic (EEG) techniques in two species (rat and cat). In immobilized rats, spectral and visual electrocorticogram analysis provides a means of studying and comparing different profiles of sedative-hypnotic drugs. As with spectral analysis, Hjorth's descriptors allow one to detect the sedative effects of drugs and to study drug interactions in acute preparations. We have evaluated the action of hypnotics on the sleep-wakefulness cycle in freely implanted rats during their maximally active period because it is easier to estimate the duration of the sedative effect. We have also examined the action of sedative-hypnotic agents in rats and cats because of the different species reactivity to drugs such as benzodiazepines. These EEG methods are of value in the development of new hypnotic agents.

Animals↗
PubMed1984

Use of 31P nuclear magnetic resonance spectroscopy and electron microscopy to study phosphorus metabolism of microorganisms from wastewaters.

We used 31P nuclear magentic resonance to study the transfer of phosphorus between Pis and polyphosphates in microorganisms involved in wastewater treatment. We showed that the transfer process is reversible and of the first order in accordance with the polyphosphate concentration. The presence of nitrates in the anoxic phase led to results similar to those obtained during the aerobic phase. (Anoxic implies absence of oxygen but presence of nitrate, whereas anaerobic implies absence of oxygen and nitrate. In bacteriology, the term anoxic is not common, and the term anaerobic implies absence of oxygen and includes the conditions under which nitrate is present.) We observed that carbon dioxide lowers the pH, which entails a hydrolysis of polyphosphates, and helium seems to stop the evolution of the cells. Further, 2,4-dinitrophenol decouples the oxidative phosphorylation and brings about a decrease in the polyphosphate pool.

Aerobiosis↗
PubMed1983

[Influence of anaerobiosis on the sterol composition of Mucor hiemalis].

Strict anaerobic cultures of Mucor hiemalis lead to major modifications of the quantitative and qualitative composition of sterols. Sterols of which the lateral chain contains an ethyl or ethylidene group in C24 are for the first time brought to evidence in a Mucorales. Isolation in the same conditions of E-ethylidene-24 (28) lanostene-8 ol-3 beta lets us suppose that sterols, which are absent in aerobic cultures, are derived from this triterpene of 32 C atoms.

Aerobiosis↗
PubMed1975

Microbial transformation of artificial estrogens of the allenolic group.

When 2,2-dimethyl 3-(2'-naphthyl 6'-hydroxy) pentanoic acid, an artificial estrogen of the allenolic acid group, was added to an exponential-phase growth culture of Neurospora crassa (in Horowitz medium), it was transformed into its hydroxylated derivative, 2,2-dimethyl 3-(2'-naphthyl 4',6'-dihydroxy)pentaoic acid. To study this transformation, radioactive 2-methyl-[2-14-C=A1methyl 3-(2'-naphthyl 6'-hydroxy) pentanoic acid has been prepared. The rate of metabolism of allenolic acids varies in the same way as their estrogenic activity.

Carbon Radioisotopes↗
PubMed1975

Arterial water, cations, and norepinephrine in early and late renovascular hypertension.

In dogs made hypertensive renal artery stenosis and contralateral nephrectomy, the arterial and myocardial tissue content of water, cations (sodium, potassium, magnesium, calcium), and norepinephrine was measured 20 and 60 days after the operation. Hypertensive animals autopsied at the earlier stage of hypertension had significantly lower (-25 to-50%, P smaller than 0.01) arterial norepinephrine than either the sham or nonhypertensive animals. The water and cation content of arteries was unchanged, but aortic tissue contained significantly more water, sodium, potassium, and magnesium than the nonhypertensives. Hypertensives autopsied at 60 days also had lower arterial norepinephrine content than sham and nonhypertensive animals, but this refuction was not significant. Their arterial and aortic tissue contained more water and cations than the nonhypertensive, sham, unoperated, and unilaterally nephrectomized dogs. It is suggested that in the initial stage of renovascular hypertension the arterial norepinephrine content is reduced significantly, whereas at a later stage the arterial water and cations may be involved in the maintenance of an elevated blood pressure.

Animals↗
PubMed1975

Effect of propranolol on plasma renin activity, renal cortex renin, and adrenal and brain isorenins in rats.

Propranolol administration to rats was studied for its effects on plasma renin activity, renal renin content, and adrenal and brain isorenins. Propranolol was given intraperitoneally at 6 and 30 mg/kg/day for a 15-day period. Pulse rate was significantly decreased. There were no effects on the isorenin content of adrenal or brain tissue or on renal renin content. Rats responded in two completely different ways with respect to plasma renin activity. Two-fifths had a total suppression of plasma renin activity; the rest had concentrations similar to those in controls. These observations are consistent with those seen during chronic administration of propranolol to hypertensive patients and suggest that its antihypertensive effect may in some patients be through the suppression of renin release. Its mechanism of action in most patients remains at present unclear.

Adrenal Glands↗
PubMed1974

Screening programs for hypertension.

MAJOR SCREENING PROGRAMS FOR HYPERTENSION ARE NECESSARY FOR THE FOLLOWING REASONS: (a) the 12 to 15% prevalence of hypertension in the North American population; (b) the high proportion of hypertensive patients who are inadequately treated or whose disease is not even recognized; (c) the fact that in too many medical centres hypertension is poorly investigated or considered an insignificant finding; (d) the demonstration by many groups, especially the Framingham study, of hypertension as the major factor in the occurrence of severe cardiovascular disease; and (e) the achievement of a marked decrease in severe cardiovascular complications following adequate treatment. But such screening programs are of little value if unaccompanied by a major educational effort directed not only to the public but also to the medical profession, and a parallel increase in the funding of biomedical research into the basic physiopathological mechanisms of hypertension.

Adolescent↗