Search PubMed⌕ Search

Biomedical subjects

C Jacquot

Publications and source records attributed to C Jacquot.

At least 235 records · Page 13Linked to original sources
PubMedDate not supplied

Experimental filariasis of Dipetalonema dessetae in Proechimys oris: 3. Effects of parasitism on the pharmacokinetics of diethylcarbamazine.

The pharmacokinetic parameters of diethylcarbamazine were compared in the plasma and peritoneal fluid of 5 non-infected rodents. In the filarial animals, the absorption rate constant and the elimination rate constant were significantly increased. The peak plasma concentration was twofold higher in the infested rodents than the control animals, and this may account for the rapid action of diethylcarbamazine on blood-circulating microfilariae. The area under the curve was unchanged. Total clearance is slightly increased in filarial rodents. These data are explained by an important reduction of renal clearance combined with a moderate increase of extra renal clearance. High levels of diethylcarbamazine in peritoneal fluid, resulting from the excellent diffusion of the drug in filarial animals explains the activity on adult worms. But the parasitism does not affect the mechanism of distribution of the drug between plasma and peritoneal liquid.

Animals↗
PubMedDate not supplied

[Experimental filariasis in Proechimys oris by Dipetalonema dessetae: 4. Effect of parasitism on protein and tissue binding of diethylcarbamazine].

Several groups of control and filaria-infected Rodents were treated by radio-labelled diethylcarbamazine in order to study the effect of parasitism on the protein binding and tissue distribution of the drug. These studies were performed using equilibrium dialysis, chromatography and autoradiography. The plasmatic protein concentrations were lower in the group of infected Rodents, due to a decrease of albumin. The binding rate depended on the electrophoretic fractions, but remained low and unaffected by parasitism. The radioactivity of DEC and its metabolites appeared very quickly in the tissues, particularly in infected Rodents. This was due to the fact that the already rapid intestinal absorption and diffusion were enhanced by filariasis.

Animals↗
PubMedDate not supplied

[Experimental filariasis in Proechimys oris by Dipetalonema dessetae. 5. Effect of parasitism on metabolism of diethylcarbamazine].

The metabolism of diethylcarbamazine (DEC) in healthy and filaria-infected Proechimys oris Rodents was investigated. DEC and 14C labelled DEC were orally administrated (100 mg/kg). The drug was quickly and intensively metabolised. About 90% of the dose administered was eliminated in the urine within 24 hours. Monodeethylation was the major pathway. The major urinary metabolites were ethylcarbamazine and its N-oxide. Traces of N methylpiperazine 2,5 dione and their N-oxide were also found. Elimination was faster in filarial than in healthy animals, but metabolites were the same.

Animals↗
PubMedDate not supplied

Pharmacokinetics of a prodrug thymoxamine: dose-dependence of the metabolite ratio in healthy subjects.

Thymoxamine, a prodrug, is rapidly deacetylated in the plasma to give two phase I metabolites, DMAT and DAT, which are further sulpho- and glucuro-conjugated and then excreted mainly in the urine. In a cross-over study, the dose-dependence of the metabolite ratio was evaluated in nine healthy volunteers after three doses (120, 240, 480 mg) of thymoxamine-HCl. Regardless of the dose, DMAT and its glucuronide were not detected, while the amount of DMAT-sulphate was found to be proportional to the dose administered. Plasma levels of DAT were measurable in only four of the nine subjects after the 480 mg dose and showed great intersubject variability. The pharmacokinetics of both DAT-sulphate and DAT-glucuronide were dose-dependent. As the dose increased, the proportion of DAT undergoing sulphatation decreased; this saturation was compensated by glucuronidation.

Adult↗
PubMedDate not supplied

Pharmacokinetics and metabolism of 14C isobytylnaphtyl acetic acid in rat.

After oral administration to rats, absorption of INAA was slow but complete. Plasma level curves reached a plateau for INAA as well as for the two metabolites, which were rapidly formed (MI and MII). The plateau concentration led to an increase of the apparent elimination half-life, which was short after i.v. administration due to the small volume of distribution and to the high rate of metabolism. In any case the half-life was independent of the dose and the pharmacokinetics of INAA remained linear from 1.5 to 15 mg/kg. The two rapidly formed plasma metabolites were eliminated more slowly than INAA. INAA and its metabolites were distributed only sparsely in all tissues under investigation, probably due to the high protein binding. Both routes of administration resulted in elimination of the radioactivity mainly by the urine. Besides the two main metabolites with known structures (MI and MII) small amounts of INAA and two additional metabolites were detected.

Administration, Oral↗
PubMedDate not supplied

Metabolism of isobutylnaphthyl acetic acid in rats: determination of the chemical structures of metabolites.

After oral and intravenous administration of radiolabelled isobutylnaphthyl acetic acid (INAA) to rats two metabolites were isolated from urine and plasma by HPLC. Field desorption, high resolution electron impact mass spectrometry as well as GC-MS after derivatization were used for structure elucidation and identification of the metabolites. The main biotransformation product in rat urine was found to be 5-(2'-hydroxy-2'-methyl-propyl)-1-naphthyl acetic acid (M1). The main metabolite in plasma was derived and was found to be 5-(2'-carboxypropyl)-1-naphthyl acetic acid (M2).

Animals↗
PubMedDate not supplied

Comparative activity of two cholecystokinin analogues with partial agonist activity: effects on food intake and brain monoamines.

Two analogues of the C-terminal heptapeptide of cholecystokinin have been synthesized, in which the C-terminal phenylalanine residue has been replaced by a phenylethylester (JMV 180) or a phenylethylamide (JMV 170) group. They have been shown to present partial agonist CCK activity on pancreatic amylase release. In this study, the effects of the two peptides were investigated on food intake and brain monoamine metabolism after intraperitoneal (IP) and intracerebroventricular (ICV) administration. Neither peptide was active on feeding after IP administration but both decreased food intake after ICV injection, with a slightly higher potency for JMV 170. JMV 180 induced no change in monoamine metabolism whatever the route of administration. JMV 170 IP decreased cortical levels of dopamine and its metabolites. This effect was stronger after ICV injection and was accompanied by changes in serotonergic metabolism in the hypothalamus and cortex. Contrary to CCK8 S, which is more active on feeding after peripheral injection, the feeding effects of the analogues obtained by modification of the C-terminal phenylalanine residue appear to involve a central site of action. Furthermore, phenylethylamide substitution (JMV 170) gives rise to greater potency on monoaminergic variations than replacement with a phenylethylester (JMV 180) and the effect is enhanced following central administration.

Animals↗
PubMedDate not supplied

Effects of glipizide on beta-endorphin concentration in the brain of genetically diabetic (db/db) mice.

Sulphonylurea drugs have been shown to augment glucose metabolism by both pancreatic and extrapancreatic actions. The regulation of glucose involves a modification of beta-endorphin secretions via central and peripheral mechanisms. beta-Endorphin participates in the regulation of feeding and is implicated both in obesity and diabetes mellitus. This study shows that glipizide could exert its pharmacological action in genetically diabetic (db/db) mice via beta-endorphin secretions by a central mechanism.

Animals↗
PubMedDate not supplied

Effects of glipizide on beta-endorphin secretions in response to hyperglycaemia in obese cafeteria rats.

Regulation of blood glucose involves the integration of the central nervous system with both hormonal and neural mechanisms. Considerable evidence suggests that beta-endorphin is involved in the regulation of feeding in experimental animals and man. Previous studies have shown that beta-endorphin plays an important role during hyperglycaemia. Glipizide has been shown to increase glucose metabolism by both pancreatic and extrapancreatic actions. This study indicates that glipizide may exert its pharmacological action in obese cafeteria rats through a modification of beta-endorphin secretions via central and peripheral mechanisms.

Animals↗
PubMedDate not supplied

Antitumor and antiproliferative effects of an aqueous extract from the marine diatom Haslea ostrearia (Simonsen) against solid tumors: lung carcinoma (NSCLC-N6), kidney carcinoma (E39) and melanoma (M96) cell lines.

An aqueous extract of the marine diatom Haslea ostrearia (Simonsen) was studied for its antiproliferative properties against human solid tumors: lung carcinoma (NSCLC-N6), kidney carcinoma (E39) and melanoma (M96). These types of carcinoma are particularly chemoresistant. The extract has a potent cytostatic effect in vitro on the three cell lines and blocks the NSCLC-N6 line in the G1/S phase of the cell cycle. Moreover, the extract strongly inhibits tumor growth of NSCLC-N6 bearing nude mice. These preliminary results indicate that the aqueous extract of Haslea ostrearia exhibits inhibitory effects both in vitro and in vivo against solid carcinoma lines, suggesting the presence of a new potent antitumor agent in the aqueous algal homogenate.

Animals↗
PubMedDate not supplied

Subtractive hybridization and differential screening identified two genes differentially expressed after induction of in vitro (atypical) terminal differentiation in the NSCLC-N6 cell line by a marine substance (bistramide K).

Non-small-cell lung carcinoma is generally refractory to chemotherapy. The difficulties that arise in the treatment of this type of tumor make it necessary to develop new therapeutic strategies. Previous work done in our laboratory showed that a marine substance named bistramide K induced in vitro (atypical) terminal differentiation of NSCLC-N6 cell line. This activity is linked to a growth arrest of NSCLC-N6 cell line and an irreversible block at the G1 phase of the cell cycle (G1DT). In order to identify the genes that could be expressed after the treatment by the drug, we constructed a subtractive cDNA library with enriched mRNA extracted from BK-treated NSCLC-N6. After differential hybridization and DNA sequencing, we identified two sequences. The sequence identified for the clone 8 showed strong homology to the sequence of the ribosomal protein L35A. The sequence identified for the clone 4 did not show any homology with known sequences in official gene data banks.

Antineoplastic Agents↗
PubMedDate not supplied

Effect of four genes (ALDH1, NRF1, JAM and KBL) on proliferation arrest in a non-small cell bronchopulmonary cancer line.

Despite new protocols, non-small cell bronchopulmonary cancers are still difficult to treat by current chemotherapeutic procedures. Thus, it is essential to define new treatment strategies and detect new therapeutic targets. In order to define these new targets, this study applied the "differential display" (DD) technique to the NSCLC-N6 cell line treated with VT1 [methyl-4-methoxy-3-(3-methyl-2-butanoyl)benzoate]. VT1 induces arrest of the NSCLC-N6 cell cycle in the G1-phase, followed by cell death. DD enabled us to detect seven overexpressed mRNAs during treatment, four of which corresponded to identified genes: aldehyde dehydrogenase 1, nuclear transcription factor Nrfl, junctional adhesion molecule, and amino-ketobutyrate ligase. An antisense strategy showed that amino-ketobutyrate ligase is involved in the proliferation arrest of NSCLC-N6 cells in the G1-phase after VT1 treatment.

Acetyltransferases↗
PubMedDate not supplied

Effect of an atypical barbiturate, the 2-allophanyl-2-allyl-4-valerolactone (valofan), on exploratory behaviour and brain serotonin concentrations in mice.

This study investigates, both behaviourally and biochemically, the action of 2-allophanyl-2-allyl-4-valerolactone (Valofan) in the mouse, after acute or repeated administration. The exploratory behaviour was measured in different experimental conditions by a hole-board test modified in observation length: 10 min instead of original 5. The variations in 5-HT and 5-HIAA levels were measured in cortex and brainstem. Acute administration of Valofan (50 to 500 mg/kg os) did not change exploration during the first 5 min period, while at higher doses (200-500 mg/kg) it did produce a significant increase in basal exploratory behaviour, measured by prolonging hole-board test to 10 min. These data were confirmed by the habituation test to he thole-board whereby, after three days of exposure, low exploratory baseline of mice was constant. The elevation of the exploration was consistant with a significant net increase in 5-HT levels (greater than 5-HT; less than 5-HIAA) in brainstem, and with a relative enhance in amine levels (= 5-HT; less than 5-HIAA) in cortex for higher doses of the drug. Modifications of serotonin mechanisms positively affect behaviour in an unfamiliar environment. Surprisingly repeated treatment (for 8 days) with Valofan did not change exploration in respect of controls. The biochemical pattern of repeated treatments showed that higher doses of drug increased 5-HT without affecting 5-HIAA levels in brainstem and cortex. Repeatedly handheld mice showed control values significantly higher than those of acute treatment. This increase in activity corresponded to a biochemical pattern similar to that obtained after acute administration of 500 mg/kg Valofan, indicating that handling affected the basal 5-HT content. Thus Valofan could stimulate exploration in mice with a low baseline, while it did not change the activity of animals with a higher baseline. Further evidence for a possible involvement of 5-HT mechanisms in the action of Valofan was given by the fatigue test. Mice, submitted to hole-board after 24 h of forced walking, showed, with 500 mg/kg, a significant decrease in exploration: action of Valofan seemed to potentiate the effects exerted by stress on serotonin turnover.

Animals↗
PubMedDate not supplied

[Acid-base disorders in status asthmaticus (author's transl)].

In 85 patinets withstatus asthmaticus, the authors have studied the acid-base balance, the blood gas tensions and various humoral parameters. The values were classified into two groups according to the PaCO2 level: below or equal to 44 torr (Group I), higher than 44 torr (Group II). In the 58 cases of Group II, there was a very close positive correlation between PaCO2 and H + ions, practically the same as that established by BRACKETT et al. [3] in experimental acute hypercapnia in man. On the contrary, the correlation derived from cases of status asthmaticus in the literature showed, in some cases, a metabolic component in acidosis. In the present work, the mean value of lactates was close to normal; there was a slow increase in protein content and hematocrit, in the two groups. The prognosis of the status asthmaticus depends on the degrees of hypercapnia: when it reaches 70 torr, mechanical ventilation is urgently needed and is the main part of the treatment; the use of additional drugs remains a matter of specific case.

Acid-Base Imbalance↗