Biomedical subjects

P Courtois

Publications and source records attributed to P Courtois.

At least 37 records · Page 2Linked to original sources

PubMed2000

Impairment by cytochalasin B of the inhibitory action of D-mannoheptulose upon D-glucose metabolism in rat pancreatic islets.

D-mannoheptulose was recently found to inhibit D-glucose metabolism in hepatocytes and pancreatic islets, whilst failing to do so in parotid cells, erythrocytes and the exocrine pancreas. In the latter three systems, however, the hexaacetate ester of D-mannoheptulose efficiently inhibits D-glucose metabolism. It was proposed, therefore, that the transport of unesterified D-mannoheptulose into cells may be mediated by GLUT2. Since cytochalasin B is known to inhibit D-glucose transport into pancreatic islet cells, it was now investigated whether the mould metabolite (0.02 mM) also impairs the inhibitory action of D-mannoheptulose (1.0 mM) upon D-glucose metabolism in rat pancreatic islets. The relative extent of D-mannoheptulose inhibitory action on D-[5-3H]glucose utilization and D-[U-14C]glucose conversion to 14CO2, as well as radioactive amino acids and acidic metabolites, was indeed much less marked in the presence of cytochalasin B (13+/-4% inhibition) than in its absence (40+/-3% inhibition). A comparable situation was not observed, however, in the case of glucose-stimulated insulin secretion, cytochalasin B augmenting insulin output to the same relative extent in the absence or presence of D-mannoheptulose. These findings support the view that the entry of D-mannoheptulose into cells may be mediated by a cytochalasin B-sensitive transport system, such as the GLUT2 carrier.

Animals↗

PubMed2000

Possible role of diadenosine polyphosphates in glucose-stimulated insulin release: effects of NaF upon metabolic and functional variables in rat isolated islets.

Diadenosine polyphosphates, such as diadenosine triphosphate (A2P3) and diadenosine tetraphosphate (A2P4), were recently proposed to participate in the stimulus-secretion coupling for nutrient-stimulated insulin release. Since NaF, an inhibitor of inorganic pyrophosphatase, was reported to lower A2P3 and A2P4 content in glucose-stimulated pancreatic islets, its effects upon metabolic, cationic, biosynthetic and secretory variables in rat pancreatic islets were investigated in the present study. Up to a concentration close to 0.1 mM, NaF failed to affect most of these variables, except for a decrease in 45Ca net uptake. Much higher concentrations of NaF (e.g. 5.0 mM) were required to cause inhibition of the metabolic, ionic, biosynthetic and secretory responses of the islets to nutrient secretagogues. Yet, even at this high concentration, NaF failed to lower the islet content in tritiated A2P3 and A2P4 in islets prelabelled with [2,8-3H]adenosine and failed to prevent the glucose-induced increase in such a content. It is concluded, therefore, that NaF may not represent a suitable tool to assess the participation of diadenosine polyphosphates in the process of nutrient-induced insulin secretion.

Animals↗

PubMed2000

Effects of D-mannoheptose and D-glycero-D-gulo-heptose upon D-glucose metabolism and insulinotropic action in rat pancreatic islets and D-glucose phosphorylation by hexokinase isoenzymes: comparison with D-mannoheptulose.

The possible use of D-mannoheptose or D-glycero-D-gulo-heptose as substitute of D-mannoheptulose for specific inhibition of D-glucose phosphorylation, metabolism and insulinotropic action was investigated in the present study. The two aldoheptoses failed to duplicate the effect of D-mannoheptulose upon the phosphorylation of D-glucose by yeast hexokinase, bovine heart hexokinase or human B-cell glucokinase. They were poorly phosphorylated by the low-Km hexokinase isoenzymes or liver B-cell glucokinase. D-mannoheptose failed to reproduce the inhibitory action of D-mannoheptulose upon D-glucose metabolism by isolated rat pancreatic islets. Whilst D-glycero-D-gulo-heptose failed to affect glucose-induced insulin release, D-mannoheptose slightly enhanced glucose-induced insulin release when tested at low concentrations (0.75-1.5 mM) and progressively decreased insulin output at higher concentration (3. 0-20.0 mM) in islets exposed to a high (16.7 mM), but not physiological (8.3 mM), concentration of D-glucose. D-mannoheptose, however, also caused a modest inhibition of insulin release evoked by 2-ketoisocaproate. It is concluded, therefore, that neither D-mannoheptose nor D-glycero-D-guloheptose can be considered as suitable substitutes of D-mannoheptulose.

Animals↗

PubMed1999

Pharmacokinetic-pharmacodynamic contributions to the convulsant activity of fluoroquinolones in rats.

The in vivo convulsant activities in rats of five representative fluoroquinolones (FQs), norfloxacin, enoxacin, sparfloxacin, fleroxacin, and pefloxacin, were compared. The experimental approach allowed distinction between the drugs' ability to reach the pharmacological receptors at the level of the central nervous system (pharmacokinetic contribution) and their ability to interact with these receptors (pharmacodynamic contribution). The presence of a methyl group on the piperazine moiety decreased the pharmacodynamic contribution to the convulsant activity by severalfold, and the ratios of concentrations of the FQs in cerebrospinal fluid (CSF) to concentrations of unbound FQs in plasma varied from about 5 to 75% as a function of lipophilicity. Interestingly, FQs with the highest intrinsic convulsant activities had the lowest levels of diffusion in CSF and vice versa. This in vivo approach provides information complementary to that of in vitro experiments and should be recommended for early preclinical assessment of a new FQ's epileptogenic risk.

Animals↗

PubMed1999

Pharmacokinetics of gliquidone, glibenclamide, gliclazide and glipizide in middle-aged and aged subjects.

Six middle-aged (42-59 years old) and six aged (71-75 years old) subjects received each, on separate days, an oral administration of gliquidone (30 mg), glibenclamide (5 mg), gliclazide (80 mg) and glipizide (5 mg). The plasma concentration of the drugs was measured before and at eight times (60 min to 24 h) thereafter. The half-life of gliclazide was higher than that of the other three hypoglycemic agents in middle-aged subjects and was the sole to be significantly increased in aged subjects. There is no obvious difference between sulfonylureas eliminated mainly by either the kidney (glibenclamide, gliclazide, glipizide) or the liver (gliquidone) in terms of the influence of aging upon their clearance.

Aged↗

PubMed1998

A new approach for early assessment of the epileptogenic potential of quinolones.

The epileptogenic potential of pefloxacin and norfloxacin, two quinolone antibiotics, was investigated in vivo in three different animal species by measuring drug concentrations in cerebrospinal fluid (CSF), which is part of the biophase, at the onset of convulsions. Interestingly, the pefloxacin-to-norfloxacin concentration ratios in CSF were virtually constant across the species (7.0, 6.6, and 6.0 in mice, rats, and rabbits, respectively), suggesting that this approach could be used to predict the relative epileptogenic potential of quinolones in humans.

Animals↗

PubMed1998

Acquisition of lexical resources from SNOMED for medical language processing.

Medical language processing depends on large-coverage, fine-grained specialized lexicons. The vast majority of existing electronic lexicons concern the English language; for other languages such as French, resources are scarce. In contrast, large medical thesauri exist in numerous languages, including French. Our goal was to study what kind of linguistic information could be extracted from thesauri into a lexicon, in which places human intervention is necessary, and what kind of issues arise in this process. We designed in this purpose a method to build a semantic lexicon from a subset of the SNOMED axes in their French translation.

France↗

PubMed1997

Nephrotoxicity of gentamicin and vancomycin given alone and in combination as determined by enzymuria and cortical antibiotic levels in rats.

The purpose of this study was to compare the nephrotoxicity of gentamicin and vancomycin alone and in combination. Thirty-two male Sprague-Dawley rats were randomized into 4 groups of 8 animals. Each group received 200mg/kg gentamicin (G) i.m., or 300 mg/kg vancomycin (V) i.v., or an association of 200 mg/kg gentamicin + 300 mg/kg vancomycin (i.m. and i.v., respectively), or 0.9% NaCl solution i.m. and i.v. (controls). To determine AAP, GGT, and NAG enzyme excretions, urine samples were taken over 24-h periods before and after the start of the experiment. A single renal cortical sample was obtained at necropsy for quantitation of antibiotic levels. No significant modifications of urinary excretions of creatinine and enzymuria were noted during the 24-h period before each drug administration or in controls. AAP, GGT, and NAG excretions were significantly increased after G and G + V injections (p < 0.001), whereas only AAP and GGT were statistically higher in rats receiving V (p < 0.05). NAG elimination (mean +/- SD) was higher in G + V (16.0 +/- 0.2 IU/mmol creatinine/24 h; p < 0.001) than g (8.8 +/- 0.6) or V (1.7 +/- 0.2). Surprisingly, mean vancomycin cortical levels decreased in the combination (827 +/- 131 vs. 1964 +/- 23 micrograms/g for V alone; p < 0.001), whereas gentamicin concentration was unchanged (826 +/- 66 vs. 839 +/- 28 micrograms/g for G alone). Determination of enzymuria allowed the nephrotoxicity of the antibiotics to be graded in the following order: vancomycin + gentamicin > gentamicin > vancomycin.

Acetylglucosaminidase↗

PubMed1997

Pharmacokinetic-pharmacodynamic contributions to the convulsant activity of pefloxacin and norfloxacin in rats.

The purpose of this investigation was to compare the convulsant activity of two quinolones differing, respectively, by the presence (pefloxacin) or absence (norfloxacin) of a methyl group on the piperazine moiety at the position 7 of their parent nuclei and consequently by their lipophilicity. An in vivo model was used, which can distinguish between ease in reaching pharmacological receptors at the central nervous system level, and ability to interact with these receptors. Male Sprague-Dawley rats (approximately 230g-300g) received an i.v. infusion of pefloxacin or norfloxacin at one of four different rates: 480, 960, 1440 and 1920 micromol/hr, until the onset of maximal seizures. This occurred after an average of 12.7 to 69.4 min. We found enough evidence to suggest that in these conditions the contribution of pefloxacin metabolites, including norfloxacin, to its convulsant activity was negligible. Doses of pefloxacin and concentrations in cerebrospinal fluid and plasma (total and unbound) at the pharmacodynamic endpoint were all independent of infusion rate, whereas only cerebrospinal fluid concentrations of norfloxacin were independent of infusion rate. The overall cerebrospinal fluid concentration of norfloxacin (47.3 +/- 9.9 micromol/liter) was about 8-fold lower than that of pefloxacin (380 +/- 27 micromol/liter), indicating that on average the "intrinsic convulsant activity" of norfloxacin is 8-fold greater than that of pefloxacin. However, total doses of pefloxacin and norfloxacin at the onset of maximal seizures were in the same order of magnitude (1500-2000 micromol/kg), suggesting that the higher ability of the more lipophilic pefloxacin to reach central nervous system compensates for its lower intrinsic convulsant activity.

4-Quinolones↗

PubMed1996

[Control of buccal peroxidases by a bacterial NADH-hypothiocyanite oxidoreductase].

Oral peroxidases (myeloperoxidase, sialoperoxidase) catalyze thiocyanate peroxidation into hypothiocyanite which is bacteriostatic or bactericidal against numerous bacterial species. NADH-hypothiocyanite-oxidoreductase is thought to protect bacteria which can express it; up to now, this enzyme activity was never purified. The present study analyzes, on one hand, the susceptibility of periodontal bacteria against hypothiocyanite and, on the other hand, proposes a purification design for the NADH-hypothiocyanite-oxidoreductase from Streptococcus sanguis, a commensal micro-organism of dental surfaces. The data suggest the importance of the bacterial biofilm on dental surfaces for production of antiseptic oxidants and for the control of their toxicity.

Anti-Infective Agents, Local↗

PubMed1995

The influence of different fluoride salts on fluoride-mediated inhibition of peroxidase activity in human saliva.

Fluoride-mediated inhibition of peroxidase potential activity in human saliva was investigated using NaF, NH4F, CaF2, Na2PO3F (MFP), SnF2 and TiF4. At pH 5.5 and for a 20 mM F concentration, the inhibition percentages increased from 2% for MFP and 5% for CaF2 to 61% for NaF and 65% for NH4F, while a 100% inhibition was observed at 10 mM for TiF4 and at 5 mM for SnF2. The inhibition was enhanced at acid pH and removed at pH 7. The inhibition could be attributed to ionized F-, except for SnF2 and TiF4, in which part of the inhibition could be imputed to the cations.

Calcium Fluoride↗

PubMed1994

Hypotheses for a re-evaluation of peroxidase activity in the oral inflammation: NAD(P)H-dependent hypohalite reduction in human neutrophils.

The balance of NADH oxidation by neutrophil lysates in the presence and in the absence of peroxidase/H2O/halide systems, pointed out a NADH oxidation excess when these hypohalite generators were actually present. This unexplained NADH consumption could not be attributed to a direct oxidation by hypohalites nor by the lysate self. Using OCI- as substrate, the NADH oxidation excess ranged from 52 to 99 mU/ml at pH 7.40 and from 446 to 1346 mU/ml at pH 6.00 (N = 6). Similar results were also found while using hypoiodous and hypothiocyanous compounds at pH 7.40 but not at pH 5.50. The authors discuss different hypotheses to explain this phenomenon and accordingly elaborate on the possible consequences of neutrophils degranulation in the oral tissues during inflammation processes.

Humans↗

PubMed1993

A comparative study of enzymuria, in the rat, of the drug combinations amikacin/vancomycin and amikacin/teicoplanin.

The aim of this study was to compare nephrotoxicity of the combinations amikacin/vancomycin and amikacin/teicoplanin. Eighteen male Wistar rats were divided into 3 groups of 6 animals each. The first group received 50 mg.kg-1 of amikacin (i.m. route) and 100 mg.kg-1 of vancomycin (i.p. route). The second group received 50 mg.kg-1 of amikacin (i.m. route) and 40 mg.kg-1 of teicoplanin (i.p. route). The third group received an isotonic solution of sodium chloride. The antibiotics were injected for a period of 6 days. Urine samples of animals were taken 24 h before the beginning of the experiment, then every day, throughout the duration of the treatment (6 days), continuing for an additional 3 days following completion of the administration of the drugs. There were no significant modifications in the urinary excretions of alanine aminopeptidase and the creatinine between the 3 groups; but in the group receiving amikacin/teicoplanin, we observed between days 3 and 8 an increase in the excretion of N-acetyl-beta-D- glucosaminidase when compared to the group receiving amikacin/vancomycin (p < or = 0.05) and to the control group (p < or = 0.01).

Acetylglucosaminidase↗

PubMed1992

Stability of cisplatin in ethylene vinylacetate portable infusion-pump reservoirs.

The stability of cisplatin in admixture stored in portable pump reservoirs was investigated. Admixtures containing 0.9 or 0.5 mg/ml cisplatin in 0.9% sodium chloride injection were placed in 80-ml ethylene vinylacetate (EVA) drug reservoirs protected from light and 1-ml quantities were withdrawn immediately after preparation and after storage for 1, 2, 3, 4, 7, 14, 28 days at +22 or +35 degrees C. Three samples for each condition from each admixture were tested for drug concentration using a stability-indicating high-performance liquid chromatographic method. No colour change or precipitation was observed, and pH values were stable for the duration of the study. Loss of water through the reservoirs was substantial only when stored at +35 degrees C for 28 days. Cisplatin is stable in the infusion fluid used for 28 days under all the storage conditions considered.

Cisplatin↗

PubMed1992

Chrononephrotoxicity in rat of a vancomycin and gentamicin combination.

The effect of time of administration on excretion of two brush border enzymes--alanine aminopeptidase (AAP) and gamma-glutamyl transferase (gamma GT), and a lysosomal enzyme, N-acetyl-beta-D-glucosaminidase (NAG) with a single high dose of vancomycin, gentamicin or a combination of vancomycin and gentamicin was studied in male Wistar rats and compared with elimination of a control group. The rats received vancomycin intraperitoneally (200 mg.kg-1), gentamicin intramuscularly (100 mg.kg-1) or the combination of the drugs by the same route. A control group received isotonic NaCl solution. The four groups of animals received a single injection at 8 a.m., 2 p.m., 8 p.m., and 2 a.m. and urine excretion values for AAP, gamma GT and NAG were determined 24 hr later. The results show that the nephrotoxicity of gentamicin + vancomycin is greater than that observed with gentamicin, which again is greater than that observed with vancomycin. Furthermore, circadian variations in renal toxicity were observed, the least occurring at 8 a.m.

Acetylglucosaminidase↗

PubMed1992

Persistence of low levels of Plasmodium falciparum resistance to chloroquine in the autochthonous population of the Central African Republic.

In Central African Republic, the first cases of resistant P. falciparum to chloroquine occurred in 1983 in non immune expatriate residents on regular chemoprophylaxis. From 1984 to 1991, 950 in vivo tests with a seven days observation period were performed in semi-immune autochtonous children living in seven towns of the country. Chloroquine treatments were given at 25 mg/kg over 3 days period to children with P. falciparum parasitaemia > 500 (634 simplified methods) or > 1000/mm3 (316 WHO standard field tests), usually asymptomatic. Until 1988, the surveys show an absence or a low frequency of chloroquine resistance (usually below 10%) according to the town; since 1989, the resistance has been present in all towns but everywhere with a frequency under 20%. None cases of R III level resistance was observed and all children became or remained asymptomatic at day 7. Until further surveys demonstrate a decreased efficacity of chloroquine, it is advised that chloroquine be used at 25 mg/kg over 3 days period as the treatment of choice in uncomplicated acute malaria in the Central African Republic.

Animals↗

PubMed1992

[The antiseptic role of saliva].

The oral flora is under the control of both immunity and non specific defense factors. The immunity factors are mostly represented by polymorphonuclears immunoglobulins Non specific defense factors include lysozyme lactoferrin high molecular weight proteins, such as mucins fibronectin and beta 2 microglobulin histidine rich proteins cystatins salivary amylases salivary peroxidase system.

Antisepsis↗

PubMed1992

Fluoride inhibition of SCN- and Cl-peroxidase activities in whole saliva and of recombinant myeloperoxidase. Influence of pH and hydrogen peroxide concentration.

Fluoride (F-) inhibition of peroxidase activity in whole saliva and of recombinant human myeloperoxidase was investigated using thiocyanate (SCN-) and chloride (Cl-) as substrates. At pH 5.5, SCN(-)-linked activity in whole saliva reduced to < 40% of its initial value at F- concentration of 20 mM, while Cl- linked activity was maintained at 90% of its initial value for the same F-concentration. Based on this Cl(-)-linked activity, the contribution of natural MP to the SCN(-)-linked activity in whole saliva can be calculated. This shows a total inhibition of SCN- dependent activity of salivary peroxidase (SP) for F-concentrations > 10 mM. At a 20 mM F-concentration, recombinant MP activity reduced to 66% of its initial value with SCN-, against 88% for Cl- as substrate. This inhibition of the SCN- linked SP activity is enhanced at acid pH for a F-concentration of 20 mM: 26% residual activity at pH 5 for whole saliva + SCN-against 93% for whole saliva + Cl-; 61% for recombinant MP + SCN- and 88% for MP + Cl-. Calculated activities for SP alone showed a total inhibition at pH 5, while the inhibition was absent at pH 6.5. F-inhibition in whole saliva could also be suppressed by the addition of hydrogen peroxide.

Adult↗