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Biomedical subjects

M Guyot

Publications and source records attributed to M Guyot.

At least 55 records · Page 3Linked to original sources

Antithrombotic activity of recombinant hirudin in the rat: a comparative study with heparin.

Hirudin, a potent inhibitor of blood coagulation, differs in its antithrombotic activity according to the source of isolation. It was therefore of interest to study recombinant hirudin. Hirudin was obtained by a genetic process from E. coli. Its antithrombotic action was investigated in an experimental (rat) model of venous thrombosis and was compared to heparin whose results are known. Heparin (400 micrograms/kg) and hirudin (12.5, 25 and 50 micrograms/kg) present an antithrombotic effect and limit the extension of an existing thrombus (p less than 0.05). Higher heparin dosages increase the bleeding time mean value (p less than 0.05) whereas hirudin does not. So, recombinant hirudin presents the same antithrombotic action as heparin but with very inferior dosage. This activity seems not dose-dependent and is associated to weak hemorrhagic effects.

Animals↗

Lung ventilation and perfusion scintigraphy in the follow up of repaired congenital diaphragmatic hernia.

To evaluate the effects of congenital diaphragmatic hernia (CDH) and pulmonary hypoplasia on subsequent lung function and development, we performed lung 133Xe ventilation and 99mTc perfusion scintigraphies in a group of infants who had undergone surgical repair of a severe left CDH with respiratory distress within the first 6 h of life. The initial lung scans performed in 15 children, 2-3 months of age, demonstrated a decreased ventilation in 7. In 9 children there was a trapping of 133Xe at the left lung base. Perfusion to the hernia side was reduced in 8 of the children. We re-evaluated 11 of these 15 patients after 1-2 years. The ventilation to the left lung was still decreased in 3, but perfusion remained decreased in 9. After 5 years, ventilation to the hernia side was normal in 4 of the 5 patients studied, whereas pulmonary blood flow was abnormal in 4. These results show a progressive improvement of ventilation with a persisting reduction of perfusion to the lung of the hernia side, suggesting a primary vascular pulmonary hypoplasia in CDH.

Female↗

Inhibition of human liver microsomal epoxide hydrolase by valproate and valpromide: in vitro/in vivo correlation.

On the basis of drug interactions with carbamazepine epoxide, it has been hypothesized that valproic acid and valpromide are inhibitors of epoxide hydrolase, but the role of epoxide hydrolase in these interactions has not been clearly established. In this study, therapeutic concentrations of valproic acid (less than 1 mmol/L) and valpromide (less than 10 mumol/L) inhibited hydrolysis of carbamazepine epoxide and styrene oxide in human liver microsomes and in preparations of purified human liver microsomal epoxide hydrolase. Valpromide (KI = 5 mumol/L) was 100 times more potent than valproic acid (KI = 550 mumol/L) as an inhibitor of carbamazepine epoxide hydrolysis in microsomes. After administration of carbamazepine epoxide to volunteers, the transdihydrodiol formation clearance was decreased 20% by valproic acid (blood concentration approximately 113 mumol/L) and 67% by valpromide (blood concentration less than 10 mumol/L). For both valproic acid and valpromide, a striking similarity exists between in vitro and in vivo inhibitory potencies. Valproic acid and valpromide are the first drugs known to inhibit microsomal epoxide hydrolase, an important detoxification enzyme, at therapeutic concentrations.

Anticonvulsants↗

[Low molecular weight heparins].

The apparition in the 80's of low molecular weight heparins (LMWHs) obtained by chemical or enzymatical splitting, modified the fields of prophylactic treatment of thromboembolic diseases. These drugs present on heparin numerous advantages: equal antithrombotic activity with a smaller bleeding risk, higher bioavailability, longer pharmacokinetic, which simplify their use. The definite mode of action remains unknown, but LMWH act at different steps like coagulation (by AT III), fibrinolysis, blood cells, endothelial cells. Further, like heparin, they can be neutralized by protamine. However the right, simple, specific biological assay which presents a good correlation with the antithrombotic activity, remained to be established.

Heparin, Low-Molecular-Weight↗

[The effect of dilutions of Apis mellifica and Apium virus on ultraviolet light-induced erythema in the guinea pig].

Dilutions of Apis mellifica (obtained from the whole bee) and Apium virus (obtained from bee venom) are used classically in homeopathy for inflammatory symptoms with edema, erythema and pruritus (Lewis triad). Using a method examining the evolution of UV induced erythema in the guinea pig, the authors show the following dilutions of Apis mellifica 7 CH(10(-14)), 9 CH(10(-18)) and of Apium virus 5 CH(10(-10)), 7 CH(10(-14)), 9 CH(10(-18)) exert an action on experimental erythema. The results are statistically significant for the dilutions at the 48th hour after irradiation.

Animals↗

Thallium-201 imaging in the follow-up of differentiated thyroid carcinoma.

Since thallium-201 imaging has been reported as a potential means of follow-up of patients with differentiated thyroid carcinoma (DTC) during ongoing thyroid suppression therapy, the authors evaluated the diagnostic sensitivity of this procedure in 31 patients known to have metastases or local recurrence. Among 51 tumor sites 201TI imaging had a detection rate of 45% whereas 84% was noted for imaging with 131I administered in therapeutic doses. Thus, even though the effectiveness of the two radionuclides is not strictly comparable due to the difference in the administered doses, Thallium imaging cannot be recommended as the only modality for the follow-up of patients with DTC. Six of the eight tumor sites negative with 131I were positive with 201TI (especially metastatic cervico-mediastinal lymph nodes). So 201TI imaging may particularly be helpful in localizing metastases or recurrences in patients with a negative 131I scan and abnormal levels of serum thyroglobulin.

Bone Neoplasms↗

Detection of anomalous systemic venous return and intraatrial baffle leakage by radionuclide angiocardiography.

The case presented here is a 27-year-old patient who was born with common atrium and left superior vena cava (LSVC). Construction of interatrial septum and intraatrial baffle with pericardium was performed 16 years ago. Radionuclide angiocardiography (RAC) showed that a substantial amount of blood flow from the LSVC was directed to the inferior vena cava through the hemiazygos vein (HAV). It also detected a baffle leak and a left to right shunt at the atrial level. Subsequent RAC after reoperation initially showed insignificant flow through the atrial baffle, major flow through the HAV, and no shunt. Repeat RAC one year after surgery showed increased flow through the baffle and diminished flow through the HAV, without a satisfying explanation. This case illustrates the value of RAC in detecting various types of cardiovascular abnormality and subtle hemodynamic changes.

Abnormalities, Multiple↗

Effects of josamycin on carbamazepine kinetics.

The steady state pharmacokinetics of oral carbamazepine in epileptic patients (n = 8) was compared before and after one week of treatment with josamycin (2 g/day). There was a small but statistically significant decrease in oral clearance of total (17%) and unbound (21.5%) drug. In spite of an unchanged AUC of 10,11-epoxide carbamazepine the ratio of metabolite to parent drug AUC was significantly decreased (20.2%). The plasma protein binding of carbamazepine and its 10,11-epoxide metabolite did not vary. The results demonstrate impairment by josamycin of the apparent clearance of carbamazepine. Care should be taken in patient receiving both carbamazepine and josamycin.

Adult↗

Immunosuppressive properties of new side chain sterol hydroperoxides and of the corresponding alcohols.

New side chain sterol hydroperoxides derived from stigmastane and their corresponding alcohols could suppress the murine or human cell lymphoproliferation induced by T and B cell mitogens. The suppressive effect is dose and time dependent. Comparison of the activities of the different compounds suggests that the position of the hydrophilic group at C-29 is of greater importance than the hydroxyl or hydroperoxide function itself. Hence a new compound stigmasta-5,24 (28) diene-3,29 diol, appears to be highly effective.

Animals↗

[Incidence of epileptic seizures in Gironde].

This survey was based on a questionnaire filled by all the neurologists and electroencephalographists of the area and completed with the files of hospitalized patients. Its aim was to ascertain all the residents of the Gironde department who experienced a first epileptic seizure during the period March 1st, 1984-February 28th, 1985. A high global annual incidence rate was found, close to 85 per 100,000 inhabitants. The age and sex-specific incidence rate was very high for elderly persons particularly for males. These figures do not represent the incidence rate of chronic epilepsy, which should be given by follow-up of this group of patients.

Age Factors↗

Grossularine-1 and grossularine-2, alpha carbolines from Dendrodoa grossularia, as possible intercalative agents.

Dendrodoine A, grossularines-1 and -2, metabolites isolated from the tunicate Dendrodoa grossularia, have exhibited a cytotoxic activity on L1210 leukemia cells in culture. The inhibition of DNA synthesis induced by grossularines and the plane structure of the alpha-carboline common moiety were in favor of an intercalative process for their mechanism of action. In fact, the results of viscometry, fluorescence quenching and DNA melting experiments clearly indicated the intercalative properties of grossularine-2 explained by its quasi-planar structure and the non-intercalative DNA binding of grossularine-1 explained by the presence of a bulky indole chain at the 2-position of the alpha-carboline ring.

Animals↗

Calmodulin during development and metamorphosis in urodelan amphibians.

Calmodulin isolated and purified to homogeneity from young larvae is very similar to that obtained from adult Pleurodeles waltlii and these proteins are almost identical to previously described vertebrate calmodulins. During P. waltlii development, an increase in total individual calmodulin content is observed after the heart beating stage. In dorsal axial muscle, calmodulin level which is very high at the beginning of larval life (premetamorphosis) decreases strikingly in the first part of prometamorphosis. Such an evolution is observed in Ambystoma mexicanum too. Then, a significant increase occurs during metamorphosis. In contrast, calmodulin level in P. waltlii cardiac ventricular muscle increases continuously from hatching to the end of metamorphic climax. Thyroxine treatment which promotes precocious metamorphosis in P. waltlii and experimental metamorphosis in neotenic A. mexicanum, induces a rapid and significant increase in muscle calmodulin concentration.

Ambystoma↗