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Biomedical subjects

J Van den Driessche

Publications and source records attributed to J Van den Driessche.

At least 19 recordsLinked to original sources

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

Constriction of the smooth muscle of rat tail and femoral arteries and dog saphenous vein is induced by uridine triphosphate via 'pyrimidinoceptors', and by adenosine triphosphate via P2x purinoceptors.

Adenosine triphosphate (ATP) and uridine triphosphate (UTP) receptors were studied by comparing the contractile responses to UTP with those to ATP in the rat tail and femoral arteries and dog saphenous vein, after endothelium removal confirmed by histology, and near abolition of relaxation to acetylcholine. Contractions induced by ATP and UTP were dose dependent, as assessed from preparations at resting tension. Contraction curves were very different: rapid subsidence with ATP and sustained contraction with UTP. In the rat tail artery and the dog saphenous vein, quinidine, nordihydroguaiaretic acid (NDGA) and phentolamine inhibited the contractions induced by ATP, whereas those induced by UTP were only slightly reduced in the presence of NDGA and were not antagonized by quinidine and phentolamine. In all three vessels, alpha-beta methylene ATP induced desensitization to ATP, whereas it did not antagonize the UTP-induced contractions. Reactive blue 2 was incapable of antagonizing contractions to ATP and UTP in these preparations. In addition, UTP-induced contractions were hardly inhibited in a calcium-free Krebs solution, whereas ATP was totally inhibited. We showed that a calcium antagonist, nicardipine, was more potent on the UTP-induced than on the ATP-induced contractions. These results showed the UTP-induced contraction to be mediated by a new class of receptors, qualified here as 'pyrimidinoceptors', for which no antagonist is known. These results were obtained in the tail and femoral arteries of the rat and from the dog saphenous vein. ATP induced contraction in these three vessels via P2x purinoceptors. P2x purinoceptors and 'pyrimidinoceptors' are localized on the vascular smooth muscle.

Adenosine Triphosphate

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

[Chemotherapy combined with Lipiodol. In vitro study of the kinetics of release of adriamycin].

Intra-arterial injection of lipiodol-adriamycin mixtures are commonly used in the treatment of hepatic tumors based on the progressive release of adriamycin. This study was undertaken to assess, in vitro, the influence of mixture formulations on the adriamycin release pattern. Eight mixtures containing 10 mg of adriamycin were tested. Adriamycin was tested in solution (mixture A) in suspension (mixture B), or in emulsions with Hexabrix 320 (mixtures C to F). Ratios between Hexabrix and lipiodol volumes were 2/1, 1/1, 1/2, and 1/4 for emulsions C, D, E, and F, respectively. Emulsions G and H corresponded to emulsions E and F, with Arlacel A as emulsifying agent. All mixtures were prepared in triplicate and added with water. Samples of 200 microliters were taken from the aqueous phase after 10, 20, 30 min, 1, 2, 4, 8, 24, 48, 72, and 120 h for adriamycin dosage. Lipiodol-adriamycin mixture formulation significantly influenced the release pattern of adriamycin. Three formulations (suspension, emulsions 2/1 and 1/4) induced the most progressive release of adriamycin from lipiodol. This release was dramatically retarded by the addition of an emulsifying agent.

Delayed-Action Preparations

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

[Heterogeneity of purinergic P2 receptors at the level of the caudal artery of the rat and the saphenous vein of the dog].

Phentolamine (10(-5) M) and an inhibitor of the lipoxygenase pathway, nordihydroguaiaretic acid (N. D. G. A.; 8 10(-6) M) antagonized the ATP induced contraction but not antagonized the UTP induced contraction on both rat tail artery and dog saphenous vein. We conclude that the receptors to ATP are distinct from receptors to UTP and that the P2 purinoceptors are an heterogeneous group.

Adenosine Triphosphate

[Epidural anesthesia during labor: comparison of 3 combinations of fentanyl-bupivacaine and bupivacaine alone].

The association of bupivacaine and fentanyl appeared as the best method of inducing satisfactory obstetrical analgesia. But the various techniques of drug administration had to be detailed; this justified the present work, a single-blind controlled trial performed on 159 primipara women at term (except one of them), randomized in four groups, after informed consent. In each group, the number of patients, the age and the degree of uterine dilatation at the beginning of the epidural anaesthesia were comparable. Epidural anaesthesia aimed to improve the maternal comfort during labour. After a first epidural injection of 10 ml, several other injections of 6 ml were carried out according to four different protocols (I, II, III, IV), with different concentrations of fentanyl (respectively 0, 0.05, 0.1 and 0.15 mg). The mean total dosages of fentanyl were statistically higher in the protocols III and IV. The foetal cardiac rhythm and uterine contractions were monitored continuously as well as maternal blood pressure and heart beats during labour. The following parameters were assessed: contraction pain intensity (five point scale), the onset of analgesia, the duration of analgesia, the length of labour, the interval between the first drug injection and subsequent injections, the type of delivery. In the newborn, Apgar score was assessed at 1, 5 and 10 min after delivery. The degree of analgesia was statistically improved in the groups receiving fentanyl, without any differences between them. On the other hand, the length of labour was shorter with protocol II (lowest concentration of fentanyl).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

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

[Undesirable dermatologic results of drugs. Result of a drug monitoring survey].

A prospective survey of drug-induced diseases has been performed along a one year period in a department of dermatology. Among the 550 patients hospitalized during this period for a cutaneomucous event, a drug-induced disease is pointed out in 30 of them (5.6 p. cent). The use of algorithm allows the establishment of the cause-effect relationship; the relative value of literature data and the role of three main predisposing factors (age, allergic antecedents, polymedication) are insisted upon. Three categories of drugs are primarily implicated: cardiovascular, antiinflammatory and antiinfectious drugs. The most commonly observed events are erythrodermia and allergic phenomena. If favorable evolution is usual, one fatal adverse drug reaction is firmly established in our series. Such a survey would lead to preventive attitudes.

Adult

[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

[Thermal degradation of tributyltin oxide and pulmonary toxicity of its combustion products in mice and guinea pigs].

Relative to an industrial application, the authors relate results obtained from a peculiar study on the thermic degradation of bis (tri-n-butyltin) oxide (TBTO) at various temperatures and they account for the toxic effects observed after inhaling the combustion products in the mouse and guinea pig. Thermolysis of TBTO between 200 and 600 degrees C gives saturated hydrocarbon and olefin gas, a condensate of tetrabutyltin and dibutyltin oxide and a residue composed of stannous or stannic oxides according to the temperature. Pulmonary toxicity is very important at low temperatures but after heating, toxic effects decrease. The results are confirmed by localisation and histopathologic studies. At 600 degrees C no death appears but some behavioral troubles occur. It's possible that repeated exposures can induce delayed toxicity.

Animals

[Comparative study of the progestomimetic and contraceptive activity of quingestanol acetate with 5 other progestational molecules].

The progestomimetic, contraceptive activities of quingestanol acetate are compared to those of five molecules (chlormadinone acetate, norgestrel, progesterone, norethisterone acetate, lynestrol). In the opinion of the authors, the therapeutic efficacity of contraceptive pills cannot be judged solely according to the weight of their various ingredients. An appreciation of the value of the various substances is based on a comparison between their physiological activity and their weight. The concept of a mini-dosage pill should therefore be considered, and due consideration paid to the physiological activity of each ingredient. In the experiments described here, quingestanol acetate shows marked statistical differences to the other five molecules.

Animals

[Effect of ascorbic acid during acute iterative anoxia, hypothesis of an anti-oxidizing mechanism of action in comparison with the effect of hydroquinone].

Some of the problems which appear during senescence, are said to be caused by cerebral oxygen deficiency and various experiments have been set up to try to imitate this particular aspect of the ageing process. We have already studied the action of many drugs with regard to acute repeated anoxia. Our work has given us clear evidence of the activity of ascorbic acid, which delays the moment of electroencephalographic silence in rats and decreases the latent period up to the reappearance of electrical activity. In order to pinpoint the mechanism of action, we compared the influence of lysine aceto-salicylate with that of hydroquinone. Very small doses of the latter drug produce a marked effect and lead us to put forward the hypothesis that it may be anti-oxydising. However, although all the drugs which proved effective in these experiments may be grouped together (despite their varying pharmacological profiles) and described as "anabiotic" drugs, it is not possible to revert to a single mechanism of action for the group as a whole.

Animals