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H Monteil

Publications and source records attributed to H Monteil.

At least 127 records · Page 7Linked to original sources
PubMed1991

Pharmacokinetic and preliminary metabolic fate of navelbine in humans as determined by high performance liquid chromatography.

The pharmacokinetics and metabolism of Navelbine (NVB) were investigated in 20 patients by a specific high performance liquid chromatographic methodology allowing the monitoring of NVB, deacetyl-NVB, and N-oxide NVB. After the i.v. (15 min) administration of 30 mg/m2 of drug, blood and urine samples were collected for, respectively, 144 and 48 h. NVB is characterized by a three compartmental kinetics, with a Cmax of 1130 +/- 139 (SEM) ng/ml. The total body clearance and apparent volume of distribution, as defined by high performance liquid chromatography, are 1.26 +/- 0.09 liter/h/kg (48.6 +/- 4.1 liters/h/m2) and 75.6 +/- 9.2 liters/kg (2918.4 +/- 307.2 liters/m2). No metabolite could be detected in serum; the urinary excretion of NVB represented 11% of the administered dose. Deacetyl-NVB could be identified as a minor urinary metabolite when no N-oxide NVB appeared in the urine samples. Two additional peaks appeared in most of urinary chromatograms as trace amounts. Thus, the major pathway of NVB, as for other Vinca alkaloids, should be hepatic clearance, as biliary elimination and/or hepatic biotransformation.

Adult↗
PubMed1991

Phosphorylation of cellular proteins in response to treatment with Clostridium difficile toxin B and Clostridium sordellii toxin L.

Toxin B from Clostridium difficile induces typical morphological changes of cultured cells consisting of rounding up and arborization, which are associated with a dramatic disruption of microfilaments. In this study, we show that toxin L, a cytotoxin produced by bacterial strain Clostridium sordellii, has similar effects on cultured cells including the redistribution of F-actin and of the adhesion plaque protein vinculin. It has been assumed that the mechanisms involved in cytopathic effects of toxin B are related to the function of an unidentified component that regulates the organization of the actin cytoskeleton. We demonstrate that the treatment of cultured astrocytes with toxin B or toxin L alters the incorporation of inorganic phosphate into several proteins. Immunoblot analysis revealed that one of these proteins is tropomyosin. Since tropomyosin stabilizes microfilaments and inhibits the severing activity of gelsolin, the toxin-induced phosphorylation may counteract this inhibition resulting in severing of microfilaments and capping of short filaments. A decrease in the radioactivity associated with intermediate filament protein vimentin was also detected using a monoclonal antibody which specifically recognizes a phosphorylated epitope of vimentin. Since vimentin is an in vivo substrate for various protein kinases, these data are in favor of broad effects of these toxins. Direct measurement of protein kinase C in cells exposed to toxin B or to toxin L did not reveal a significant change in protein kinase C activity. Furthermore, treatments with toxins do not increase cAMP levels, suggesting that toxins do not activate protein kinase A. Although further studies are required to determine the primary target site for the clostridial cytotoxin B and L, our results show that they provoke the alteration in the phosphorylation of cellular proteins.

Actin Cytoskeleton↗
PubMed1991

[Diffusion of roxithromycin in gingival tissue].

The gingival penetration of roxithromycin was evaluated at steady-state in twenty nine patients treated by 150 mg orally every 12 h during five days. Tissue specimen were sampled at 2 h (n = 6), 4 h (n = 6), 6 h (n = 5), 8 h (n = 6) and 12 h (n = 6) after the 10th administration. One blood sample was drawn at the same times. Serum and tissue concentrations of roxithromycin were measured by high performance liquid chromatography (HPLC). Serum peak level, measured at the 4th h, reached 6.60 +/- 1.15 micrograms/ml. The tissue peak concentration was 4.63 +/- 1.84 micrograms/g at the 8th h. Between the 4th and 10th hour after administration, the tissue concentrations are above 2 micrograms/g, i.e. above roxithromycin MIC 90 against most of the encountered pathogens in stomatologic infections.

Bacterial Infections↗
PubMed1991

[Experimental study on the hepatobiliary kinetics and excretion of temafloxacin. Evidence for production of active metabolites by the rabbit liver].

Temafloxacin is a new fluoroquinolone derivative currently under evaluation. Its hepatobiliary disposition remains undefined as yet. The present study represents an experimental approach to this issue. Six isolated rabbit liver preparations were perfused for three hours with reconstituted and oxygenated blood in a closed circuit. A the onset of the procedures, temafloxacin 10 mg were added to the circulating blood. Both bile and blood were sampled throughout the perfusion time, and liver fragments were taken at the end of the experiments. Temafloxacin levels were measured by HPLC in serum and hepatic tissue, and by both HPLC and microbiological assay in bile. The percentage of drug undergoing hepatic biotransformation appeared to be high, i.e. 58.3%. This finding is substantiated by the comparison of temafloxacin levels in bile, as provided by HPLC and microbiological assay, the latter yielding concentrations twice as high (biliary peak: 33.5 +/- 2.8 micrograms/ml versus 19.3 +/- 3.1 micrograms/ml by HPLC assay) as those obtained by HPLC (p less than 0.05). Consistently, the average amount of temafloxacin excreted into the bile (0-3 h) was, respectively, 92 micrograms (0.9% of the dose) and 204 micrograms (2.0%) as determined by HPLC and microbiological methods (p less than 0.05); this statistically significant difference suggests the presence of active metabolites in bile. The presented results bring out evidence for substantial biotransformation of temafloxacin by Rabbit liver. Extrapolation to other species, however, would be hazardous; further pharmacokinetic studies are needed in order to assess the relevance of these findings in humans.

4-Quinolones↗
PubMed1990

High-performance liquid chromatography of antibiotics.

High-performance liquid chromatographic (HPLC) monitoring of antimicrobial agents has recently become more widely used, and represents an interesting alternative to other methods. The methodology is characterized by good specificity and accuracy, and it is applicable to almost all antibiotics. This review first describes the successive steps to investigate for the development of an HPLC method for a new antibiotic, and how to make use of it. Particular emphasis is put on the problems related to the standardization of sample preparation and to the development of mobile phases for use with different molecules belonging to the same class. The second part of the review describes one or more HPLC techniques for a representative antibiotic of each major class.

Anti-Bacterial Agents↗
PubMed1990

Fast purification of Clostridium sordellii cytotoxin.

We have developed a rapid method for the purification of proteins, combining titration curve analysis with a two-step column chromatographic procedure. We have used this approach to purify the cytotoxin (L toxin) from Clostridium sordellii. We have also determined the amino acid composition of this cytotoxin. This toxin has a pI value of 4.20 and an Mr of 260,000, reduction of which results in a band of Mr 43,000 on sodium dodecyl sulphate polyacrylamide gel electrophoresis. Since both the proteins of Mr 260,000 and 43,000 are recognized by the polyclonal anti-C. sordellii L toxin, which neutralizes the L toxin cytotoxicity, we propose a hexameric structure for the protein of Mr 260,000, each subunit being Mr 43,000.

Amino Acids↗
PubMed1990

Single oral dose pharmacokinetics of the two main components of pristinamycin in humans.

A preliminary study of the pharmacokinetics of the two main components of pristinamycin, PIA and PIIA is reported. A single oral dose of 2 g of pristinamycin was administered to six patients with normal renal and hepatic function. The samples were withdrawn during 9.5 h and assayed by HPLC. PIA and PIIA plasma levels evolved in parallel in each subject and their kinetic parameters were comparable: Tmax of 3.25 +/- 1.80 h and 3.08 +/- 1.98 h, Cmax of 0.760 +/- 0.427 mg/l and 0.581 +/- 0.285 mg/l, elimination half-life of 4.03 +/- 2.77 h-1 and 2.83 +/- 0.75 h-1, respectively. The relative proportions of PIA and PIIA, which govern the antibacterial activity of the mixture, were maintained during the study in the range of values leading to 90-100% of optimal activity against Staphylococcus aureus. The sum of the plasma concentrations of PIA and PIIA, which can be considered to be equivalent to the concentration of total pristinamycin, was superior to the MICs for the most susceptible staphylococcal strains during the entire period of study. On the other hand, the sum of PIA and PIIA concentrations exceeded the MICs for the less susceptible strains for only 4 h. These results differ from the scanty pharmacokinetic data presently available, which were obtained by microbiological methods.

Administration, Oral↗
PubMed1990

Enzyme immunoassay (ELISA) for detection of Clostridium difficile toxin B in specimens of faeces.

Antisera against Clostridium difficile toxin B were prepared in sheep and rabbit and were used in indirect and sandwich enzyme-linked immunosorbent assays (ELISA) for the detection of toxin B. Polyvinyl chloride and polystyrene microtitration plates were tested as solid phases for the assay. Both assays had a lower limit of detection for toxin B of 1 ng/ml. They were used to detect the presence of toxin B in 210 human faecal specimens and also in the culture supernatant fluids of C. difficile strains isolated from the faecal samples. There was a close correlation between the results of sandwich ELISA and those of cytotoxicity tests and isolation of C. difficile. Our sandwich ELISA method seems to be useful as a presumptive test for detection of C. difficile toxin B.

Bacterial Proteins↗
PubMed1990

Biliary pharmacokinetic profile of piperacillin: experimental data and evaluation in man.

The purpose of the present experimental and clinical work is to revisit the biliary pharmacokinetic properties of piperacillin. Whereas the up to now published data result from microbiological assays, this work was realized by high performance liquid chromatography. In the isolated and perfused rabbit liver model (n = 5; 3 h), the biliary level peaked at 1,013 +/- 305 micrograms/ml between 30 and 60 min. During the experiments, 56.7% and 10.8% of the administered piperacillin (10 mg) were respectively eliminated in bile and submitted to hepatic biotransformation. In man, a single 2 g i.v. dose was administered to 6 volunteers. The excretion measured in the duodenal fluid was 1,681 +/- 601 micrograms in 4 h (0.08% of the administered dose). In cholecystectomized patients (n = 10) provided with a T-drain, the biliary peak concentration was 211 +/- 64 micrograms/ml during the 2nd h, and the 24 h biliary elimination was 12,963 +/- 3,332 micrograms, representing 0.65% of the administered dose. The hepato-biliary clearance was 0.80 ml/min. On per-operatively collected serum, choledocal bile, gallbladder bile and gallbladder wall samples (n = 10 patients), the concentrations of piperacillin simultaneously measured 1 h after the i.v. administration of 2 g were respectively, 81.7 +/- 20.5, 382 +/- 110, 30.8 +/- 2.5 micrograms/ml and 10.5 +/- 2.6 micrograms/g.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Biliary elimination and hepatic disposition of piperacillin: experimental evaluation].

The rate of biliary elimination and the hepatic disposition of piperacillin were studied by using an experimental model of a three hours perfusion of five isolated rabbit liver preparations. After addition of 10 mg of the antibiotic to the circulating blood, a mean biliary peak of 1,013 +/- 305 micrograms/ml was obtained between the 30th and 60th minute. The cumulated biliary elimination (0-3 hr) amounted to 5,665 +/- 389 micrograms (56.7% of the dose given). The hepatobiliary clearance was calculated to 134.2 ml/hr and the biliary elimination rate constant to 0.5 545 (h-1). After the procedure, 7.2 +/- 2.7% of the dose of piperacillin was still present in the circulating blood and 0.4 +/- 0.1% in the liver. The degradation of the antibiotic in the perfusion device concerned 24.9% of the dose. The percentage of piperacillin undergoing hepatic biotransformation, calculated by subtraction, was 10.8%. Under these conditions, the biliary elimination of piperacillin is much higher than that of the twenty other beta-lactams studied in our laboratory by the same experimental procedure.

Animals↗
PubMed1989

High-performance liquid chromatography for the determination of three new fluoroquinolones, fleroxacin, temafloxacin and A-64730, in biological fluids.

High-performance liquid chromatographic procedures have been developed for the measurement of three new fluoroquinolones, fleroxacin, temafloxacin and A-64730, in serum, urine and bile. The sample treatment consists of a two-step chemical extraction. The three molecules are chromatographed on a C18 reversed-phase analytical column with spectrofluorimetric detection. At a signal-to-noise ratio of 4, the detection limits in serum are 2.5, 10 and 20 ng/ml, for fleroxacin, temafloxacin and A-64730, respectively. The calibration curves are rectilinear between these detection limits and 20 micrograms/ml. The intra- and inter-assay coefficients of variation are in the ranges 0.8-5.4 and 2.2-7.6%, respectively. These simple and reliable assay procedures will be of great interest for further pharmacokinetic studies and drug monitoring in hospital use.

Anti-Infective Agents↗
PubMed1989

Clostridium difficile toxin B: characterization and sequence of three peptides.

The cytotoxin, also named toxin B, was isolated from a toxigenic strain of Clostridium difficile, purified to homogeneity and partially characterized. The purification procedure included ultrafiltration followed by anion-exchange chromatography. We noticed that a non-specific nucleic material eluted with the protein during the purification. The presence of these nucleic acids appeared to be important for the toxic activity of the protein. Some characteristics of the cytotoxin were examined, especially the amino acid composition and the sequence of three tryptic fragments.

Amino Acid Sequence↗
PubMed1989

Purification and characterization of Aeromonas hydrophila beta-hemolysin.

Aeromonas hydrophila hemolysin was excreted in our culture conditions during the stationary growth phase. The toxin was purified to homogeneity by a three-step method: ultrafiltration, acid precipitation in the presence of RNA and anion exchange chromatography with FPLC apparatus. Beta-hemolysin is a protein not associated with lipids, carbohydrates or nucleic acids whose subunit mol. wt is 51,000. The mol. wt determined by polyacrylamide gel electrophoresis suggests that the molecule is in a trimeric form. The toxin is thermolabile and inactivated by proteolytic enzymes such as trypsin, chymotrypsin, pronase, subtilisin and proteinase K. Antibodies raised against the beta-hemolysin neutralize both hemolytic and cytotoxic activities. When injected at high dose, this purified hemolytic protein causes a positive rabbit ileal loop test, thus indicating that beta-hemolysin could be the main virulence factor involved in intestinal symptoms.

Aeromonas↗
PubMed1989

New serotypes of Pseudomonas cepacia.

O and H serotyping of Pseudomonas cepacia has provided a suitable procedure for epidemiological studies. Our previous reports have described 7 O and 5 H antigens. The study of strains from another geographical origin led us to prepare antisera against those which could not be serotyped and thus to determine 2 new O and 2 new H specificities (O:8 and O:9, H:4 and H:8).

Antibodies, Bacterial↗