Structural studies of pig lens aldose reductase: reversible dimerization of the enzyme.
Explore the source record for details and available documents.
Aldehyde Reductase↗
Biomedical subjects
J M Reymann
Publications and source records attributed to J M Reymann.
[Anxiolytic agents and hypnotic drugs in Bretagne. Pharmaco-epidemiological study].
A pharmacoepidemiological survey was carried out in a rural region of France (Brittany) with the help of 54 general practitioners, all of whom belong to a clinical research group. The aim of the survey was 3-fold: to determine the frequency (incidence and prevalence) of anxiolytic and hypnotic drug prescriptions, the sociological characteristics of these drug consumers, and the indications and reasons for prescribing this class of drugs. The population of hypnotic drug and sedative consumers was strikingly dominated by women, 60 years old and over, retired or without a profession. Prescription analysis revealed that these drugs were essentially benzodiazepines whose prevalence and incidence were 17 and 1.76%, respectively. A high frequency of prescription renewals (78%) and an elevated percentage of long-term treatments (more than 9 years) were also noted. Insomnia and dependence are the two main "risk factors" for drug treatments lasting more than one year.
Adult↗
Comparison of three regimens of Parlodel-SRO in levodopa-treated parkinsonians: a randomized double-blind crossover study.
Parlodel-SRO is a newly developed slow-release formulation of bromocriptine, which prevents initial plasma peak--a known source of adverse events--and extends the half-life of the compound, an interesting feature for the management of motor symptoms in Parkinsonians. This study was designed to determine the best daily administration schedule for 30 mg Parlodel-SRO in 18 parkinsonians previously treated with levodopa and standard Bromocriptine (Br). The 30 mg dose was replaced from one day to the next, in a randomized, double-blind latin square design trial. Three consecutive 7-day courses were implemented, during which a total daily dose of 30 mg P-SRO was administered in one dose, two intakes (b.i.d.) and three intakes, (t.i.d.) respectively. The b.i.d. schedule produced the best improvement in UPDRS scores, especially as to postural stability, walking, bradykinesia; it also provided greater pharmacological stability throughout the assessment day. Adverse event analysis was not in favor of a single daily dose. It appeared that P-SRO administered in two 15 mg intakes (morning and evening) produces the best benefit-risk ratio in Parkinsonians who were already being treated with levodopa.
Adult↗
Progress in understanding the pathophysiology of cerebral ischemia: the almitrine-raubasine approach.
Cerebral ischemia occurs frequently and is disabling. In addition to preventing and correcting risks factors, drugs prevent cell death induced by ischemia-hypoxia. Precise knowledge of the pathophysiology of cerebral ischemia is the prerequisite for drug development, and the main proofs of efficiency are histopathological and clinical (i.e., the results of controlled studies). Different animal models are considered valid for global, focal, or multifocal ischemia. These models have enabled the identification of deleterious phenomena that could be corrected or neutralized by drugs: hypoxia, lactic acidosis, release of neurotransmitters, influx of calcium, activation of phospholipase A2, release of excitatory amino acids, excess of free radicals, and neuronal cell metabolic paralysis (decrease of oxygen and glucose consumption). The chronology of these events clearly described herein will prompt the choice of the best drug, based on the delay between the ischemic event and the decision to treat. The main pharmacological effects required are the following: antagonism of hypoperfusion, oxygenation improvement, blockade of calcium influx and neurotransmitters action, reduction of acidosis and potassium efflux, blockade of arachidonic cascade and free radicals production, and antiedematous effect. The analysis of almitrine-raubasine (Duxil) pharmacological properties will be used as an example of these potentially anti-ischemic drugs. Almitrine-raubasine pharmacological studies indicate that this drug has several beneficial effects on cerebral ischemic processes. These studies have dealt with effects of hypobaric hypoxia on deoxyglucose uptake in the rat, protective effects on permanent or temporary cerebral ischemia-induced neurobehavioral problems in the gerbil, and preservation of the glycogen content and of the swelling in astrocytes after bilateral occlusion of the carotid arteries in the rabbit.
Almitrine↗
Randomized double-blind trial of injectable heptaminol for controlling spontaneous or bromocriptine-induced orthostatic hypotension in parkinsonians.
Heptaminol is a molecule with experimental cardiovascular analeptic properties. In this double-blind vs placebo trial, the potency, so far unproven, of the injectable form of a 626 mg dose of heptaminol chlorhydrate on spontaneous or induced orthostatic hypotension (OH), was assessed. Nineteen patients were included in the study: 7 displayed spontaneous OH, and in the other 12 OH was induced by bromocriptine, as monitored 103 min/after an oral intake of 6.6 mg on average. Neither spontaneous nor induced OH were recorded in 32% of the Parkinsonian population registered, with no obvious distinctive characteristics. Potency tilt-trials, performed 15, 30 and 45 min after parenteral administration of heptaminol, revealed a significant and expressive potency of the molecule on the systolic blood pressure after 15 min (P less than 0.05). Clinical and biological tolerance was excellent. Low plasma renin activity and the absence of response to orthostatism indicated, in this population of Parkinsonian extrapyramidal syndromes, a loss in positive tonus likely to be of sympathetic origin. The anti-hypotensive action of heptaminol does not seem to be related to any renal or even sympathetic interaction.
Blood Pressure↗
[Development of memory-improving drugs].
Knowledge on the diverse processes involved in memory has been gained from multiple approaches, all necessary for the development of molecules aimed at enhancing memory. However, the neurobiological aspects of apprenticeship and memory remain to be fully elucidated. Long-term storage of information in the nervous system is under the control of glycoprotein synthesis. The chemistry of storage has been extensively studied in mollusks because of their simple neuroarchitecture. In mammals, the phenomenon of hippocampic long-term potentialization (HLTP), to a large extent linked to modification of glutamatergic transmissions, has been demonstrated. Stimulation of N-methyl-DL-aspartase (NMDA) receptors induces an influx of calcium, which is needed for HLTP maintenance, as are the activation of protein kinase C (PKC) and the synthesis of new proteins, for example calmodulin. At the molecular level, a cascade of biochemical events leads to modifications of neuronal connections, thus constituting the basis of memory. Memory-improving substances can be classified according to their theoretical mechanism of action: molecular pharmacology (agents inducing phenomena that mimic HLTP), neurotransmission (molecules acting on the cholinergic, noradrenergic, serotoninergic, GABAergic or dopaminergic systems), pathophysiology (substances antagonizing or correcting anomalies responsible for the memory deficiency, i.e., the cognitive enhancers). The development of memory-enhancing drugs has encountered many obstacles, notably the difficulty in evaluating the effectiveness of a medication in improving memory. It is imperative that guidelines be established for the clinical and experimental development of such substances as well as the standardization of tests in animals and man.
Animals↗
Comparative evaluation of scavenger properties of exifone, piracetam and vinburnine.
The involvement of radical reactions in the ageing process, physiological as well as pathological, is well demonstrated. It is accepted that alloxan cyto-toxicity is linked to a production of hydroxylated free radicals and that a substance preventing the development of alloxanic diabetes possesses scavenger properties. The objective of this work was to demonstrate, in this model, the anti-radical effect of 3 molecules recommended in the treatment of cerebral insufficiency and a reference substance (+)-catechin. We observed a protective action with catechin (P less than 0.05) at the highest dose (100 mg/kg). PEG alone was moderately active but comparison of PEG-alloxan and PEG-exifone-alloxan showed a highly significant difference (P less than 0.001) at the two highest doses (60 and 120 mg/kg). Piracetam (200 and 400 mg/kg) and vinburnine (7.5 and 15 mg/kg) were inactive. Under these experimental conditions, exifone demonstrated remarkable anti-radical properties.
Animals↗
Lack of pharmacokinetic influence on levodopa by bromocriptine.
Explore the source record for details and available documents.
Bromocriptine↗
Randomized, double-blind trial of exifone versus cognitive problems in Parkinson's disease.
Exifone is a novel substance of the benzophenone group that possesses potent scavenging properties. Initial findings demonstrate beneficial effects on age-related cognitive disorders. In this double-blind clinical trial versus placebo, the efficacy of 2 dosages (600 and 1200 mg/d) was evaluated with regard to Parkinson's disease (PD)-related cognitive disorders, for which there is increasing suspicion of a free-radicals origin. Despite disparities between the treatment groups as assessed by validated scales and subtests, and a considerable placebo effect on main parameters, both dose levels of exifone produced statistically significant improvement of the cognitive items most commonly impaired by PD: immediate recall, naming of objects presented, spatiotemporal orientation, and calculation. These properties suggest a new slot for exifone in the range of therapeutics available.
Aged↗
[Cerebral edema: intra-cellular or extra-cellular mechanisms?].
Many cerebral pathological processes are attended by edema defined as an increase in brain volume associated with an increase in brain water and sodium contents. The aggravation of lesions induced by this edema warrants a pharmacological and therapeutic approach based on a detailed knowledge of its physiopathological mechanisms. Experimental models and in vitro studies have shown that the fundamental mechanisms leading to edema are: cold, acute hypoxia, ischaemia, arachidonic acid, toxic substances and plasma hypo-osmolarity. To the various types of edema described (vasogenic, cytotoxic, hydrocephalic) correspond different mechanisms. Vasogenic edema essentially depends on osmotic and hydrodynamic factors; cytotoxic edema results from perturbations in energy-dependent cellular osmoregulation. The underlying biochemical disorders have now been demonstrated, mostly in ischaemic edema; they include, during the revascularization phase, disruption of the blood-brain barrier (vasogenic component) and changes in ion concentrations, neurotransmitters and energetic mechanisms. Key factors in the development of edema are cyclic AMP, serotonin and Na-K-ATPase.
Animals↗
Aminergic neurotransmitter and water content changes in rats after transient forebrain ischemia.
We have studied changes of cerebral monoamine metabolism and water content, during recirculation following global transient ischemia (20 min) using the four-vessel occlusion model in rats. Levels of monoamines and their metabolites were determined in cortex, striatum, hippocampus, and hypothalamus. Water content was evaluated by weight and by the analysis of T1 and T2 relaxation times in 1H-nuclear magnetic resonance. Norepinephine levels decreased; 3,4-dihydroxyphenylethylamine, 3,4-dihydroxyphenylacetic acid, and 5-hydroxytryptamine levels oscillated and levels of the end products homovanillic acid and 5-hydroxyindole-3-acetic acid increased. The regional changes were qualitatively similar but quantitatively different, and were greatest in the hippocampus, illustrating the concept of neuronal selective vulnerability. The changes suggest an initial monoamine depletion and catabolism due to massive release from stores followed by autoregulatory processes. The water content increased moderately, with a maximum at 1 h. The variations of T1 were similar, positively correlated with water content and more pronounced in the cortex than in the white matter. T2 was markedly altered over the entire 24-h period. Those latter parameters are positively correlated with 5-hydroxytryptamine concentration in the hypothalamus consistent with a relationship between 5-hydroxytryptamine and cerebral edema.
3,4-Dihydroxyphenylacetic Acid↗
Comparison of the influence of dihydroergotoxine on cerebral oxygenation in the normoxic and hypercapnic hypoxic dog.
50 bastard dogs are anesthetized by chloralose (100 mg/kg) and mebubarbital (5 mg/kg) and then perfused by three-different dosages of dihydroergotoxine (DHET) (1.25; 2.5; 5 micrograms/kg/min). The effect of DHET on cerebral oxygenation is analyzed under two conditions: normoxia and hypercapnic hypoxia. The following biochemical and physiological parameters are studied: mean vertebral flow (MVF), aortic arterial pressure (AP), heart rate (HR); pO2, pCO2, total CO2, pH, haemoglobin saturation ratio, both in arteries and veins. Other parameters are calculated: O2 arterio-venous difference, CMRO2, O2 extraction coefficient, cerebral O2 supply, vertebral resistance. Under normoxia, DHET, whatever the dosage, induces a decrease of the MVF associated with an inconstant decrease of oxygen supply. At 2.5 micrograms/kg/min, a permanent and significant increase of CMRO2 is obtained. At 5 micrograms/kg/min, similar results are obtained although the decrease of HR and AP is more pronounced. Under hypoxia, the arterio-venous oxygen content difference and the CMRO2 are increased by DHET (2.5 micrograms/kg/min) without any repercussions on AP and MVF (hypothetical role of the blood pH decrease). In conclusion, DHET doubles the CMRO2, as a consequence of an increase of the oxygen extraction ratio. A 2.5 micrograms/kg/min dosage is by itself able to give this maximum effect without any major consequences on HR, AP and MVF. This effect is still obtained in hypoxia without any peripheral vascular effect.
Animals↗
Impairment of acquired temporal response regulation of rats under normobaric hypoxia.
Effects of hypoxia on learning involving temporal regulation of behaviour was investigated. Under 10% hypoxia there was a decrease in the number of conditioned responses, and the 'efficiency' of reinforcement, but no modification of temporal discrimination. Normobaric hypoxia may be a useful model for studying certain behavioural and pharmacological effects of cerebral circulatory insufficiency, and their implications at the level of the central nervous system, but it would be incorrect to use such a model to study factors that might prevent the loss of acquired knowledge.
Animals↗
[Epidural anesthesia using the bupivacaine-fentanyl combination for cesarean section].
This prospective study was designed to evaluate the benefit of a bupivacaine-fentanyl mixture vs bupivacaine alone in epidural anaesthesia for caesarean section. In 10 women, 0.5% bupivacaine (1.18 ml per metamer) was injected in the epidural space. In 20 women, 0.5% bupivacaine (1.06 ml per metamer) was injected by the same route together with fentanyl (1.70 +/- 0.09 micrograms X kg-1). The bupivacaine-fentanyl group showed a significantly shortened onset of analgesia (p less than 0.001), as well as a significant reinforcement of this analgesia graduated from 0 to 4 (p less than 0.01 at 25 min, p less than 0.001 at 75 min and at the maximum of pain, for the two sets of scores). All the Apgar scores were maximal at 5 min. No clinical respiratory depression was observed in either the mothers or the neonates. Fetal and maternal blood concentrations were in favour of respiratory innocuousness of the method (peak fentanyl concentrations: in mothers 1.5 ng X ml-1, in neonates 0.8 ng X ml-1). Fentanyl never induced any significant haemodynamic variations. Pruritus and nausea respectively occurred in six and two patients respectively in the bupivacaine-fentanyl group. In conclusion, in caesarean section, the adjunction of fentanyl to bupivacaine significantly improved analgesia without any clinical respiratory depression both in the mother and the neonate.
Adult↗
[Pharmacokinetics of intravenous ranitidine and its effect on gastric acid secretion stimulated by pentagastrin in the cirrhotic].
The pharmacokinetics of 50 mg intravenous ranitidine and the consequences on pentagastrin (2 micrograms/kg/h)-stimulated gastric acid secretion were studied in ten cirrhotic patients. Group I (n = 5) included patients without ascite; group II (n = 5) was characterized by the presence of ascites. Blood creatinine was normal in all the subjects. In non-ascitic cirrhotic patients, pharmacokinetic parameters are similar to those published in healthy subjects. In group II ascitic cirrhotic patients, the half-life is significantly increased by 50 p. 100 (P less than 0.05), as compared to group I, due to a 38 p. 100 decrease of total clearance and to a 45 p. 100 decrease of renal clearance (P less than 0.05). Hepatic clearance and volume of distribution are similar in both groups. The percentage of the inhibition by ranitidine of pentagastrin-stimulated acid out-put, in 6 cirrhotic patients, is 95 +/- 4 p. 100 (SD) when measured at the maximal inhibition peak, and 71 +/- 4 p. 100 (SEM) on the average, during the 3 h following the injection. In conclusion, ranitidine may be considered as an effective anti-secretory drug in cirrhotic patients; the pharmacokinetic variations observed in ascitic cirrhotic patients are the result of the decrease of ranitidine renal clearance.
Aged↗
[Study of three biocides (dimethoate, parathion ethyl and zineb) on female rat neuro endocrinological balance (author's transl)].
The authors studied the neuro endocrinological effects of three pesticides. Two of them were organophosphorus compounds (ethyl parathion and dimethoate) and one was a carbamate (zineb). Mature female rats have been orally administered these compounds for 16 days at respectively 1/25, 1/10 and 1/10 of the LD50. The parameters recorded are: the gonadotropins, the length of estrous cycle and the weight of the anterior pituitary gland, the ovaries and the uterus. In contradistinction with the organochlorine compounds the organophosphorus did not induce any disturbances in the neuro endocrinological system, whereas the carbamate compound decreased the pituitary gonadotropins.
Animals↗
[Does bromocriptine act through the autonomic nervous system?].
Explore the source record for details and available documents.
Autonomic Nervous System↗
The use of bromocriptine for testing central dopaminergic reactivity.
A single oral intake of 10 mg of Bromocriptine can modify both plasma renin activity (PRA) and arterial blood pressure (BP). The changes in both variables depend on the integrity of the central dopaminergic systems. The parkinsonians whose extrapyramidal symptoms are markedly improved by L-Dopa in association with a decarboxylase inhibitor (IDC) and the untreated parkinsonians are the only patients whose PRA and BP are lowered 1 h after Bromocriptine ingestion. The results obtained in the L-dopa-induced dyskinetic parkinsonians are similar to those obtained in the group of L-Dopa-resistant patients. This points to the paradoxical hypothesis of dopaminergic hyposensitivity in the dyskinetic patients. In spite of the absence of correlation between PRA and BP, it is possible that lowering of BP by Bromocriptine is linked to the parallel decrease of PRA. An increase of the BP may be obtained in the dyskinetic and L-Dopa-resistant groups. These data point to a possible involvement of central dopaminergic systems in some aspects of hypertension.
Blood Pressure↗