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Biomedical subjects

B Rouveix

Publications and source records attributed to B Rouveix.

71 records · Page 4Linked to original sources

Effect of in vivo treatment by dexamethasone and indometacin on DNA synthesis in rat macrophages in culture stimulated by inflammatory exudate.

The acute inflammatory exudate obtained 4 hr after intrapleural injection of dextran in rats is able to induce DNA synthesis and division of normal rat macrophages in culture. The influence on this phenomenon of two types of pretreatment of rats with dexamethasone or indometacin has been investigated. Exudates of rats treated with dexamethasone decreased the DNA synthesis in control macrophages. On the contrary, exudates of rats treated with indometacin had no effect on this DNA synthesis. These results could be explained by the different actions of the two anti-inflammatory agents on cellular migration in pleural exudates. In macrophages harvested from rats treated with dexamethasone or indometacin the DNA synthesis induced by inflammatory exudates was decreased. This identical response elicited by these two agents could be related to their direct antimitotic activity on macrophages.

Animals↗

[Modification of chromatin condensation in cultured macrophages during induction of cell division by an inflammatory exudate].

The determination of chromatin condensation in rat peritoneal macrophages in culture showed a predominance of heterochromatin with low transcriptory activity. After induction of division in rat peritoneal macrophages in culture by an acute inflammatory exudate, a decrease of heterochromatin and an increase of euchromatin were observed. This result brings further evidence to support previous observations according to which this type of exudate shows mitogenic properties.

Animals↗

Pharmacokinetics of a new oral formulation of amoxicillin.

The bioavailability of the recently developed 1 g dispersible tablet form of amoxicillin (B) and the 1 g dispersible tablet in suspension form (C) were compared to that of the 1 g standard reference formulation (A). Twelve healthy volunteers were involved in this single-dose, open, randomized, three-way cross-over study. The mean peak serum levels were 14.1 +/- 4.1 micrograms/ml after A, 15.1 +/- 3.1 micrograms/ml after B and 15.1 +/- 5.4 micrograms/ml after C. The area under the drug concentration versus time curves were 47.6 +/- 12.0 micrograms.h/ml after A, 52.8 +/- 10.2 micrograms.h/ml after B and 51.1 +/- 13.8 micrograms.h/ml after C. On the basis of these two pharmacokinetic parameters, the three formulations were found to be bioequivalent. In addition, the predicted serum concentrations during multiple dosing (3 times a day), derived from the corresponding mean concentrations after a single 1 g dose of C showed that 8 hourly administration would yield therapeutic serum concentrations for infections such as uncomplicated community-acquired pneumonia due to susceptible or less susceptible strains in otherwise healthy subjects.

Administration, Oral↗

Pharmacokinetic parameters and killing rates in serum of volunteers receiving amoxicillin, cefadroxil or cefixime alone or associated with niflumic acid or paracetamol.

Pharmacokinetic parameters and killing rates in serum of volunteers receiving amoxicillin, cefadroxil or cefixime alone or associated with niflumic acid or paracetamol were studied. Niflumic acid (250 mg) or analgesic and antipyretic drugs such as paracetamol (500 mg) are often combined with antibiotics to avoid inflammation and pain in acute ear, nose and throat diseases. Pharmacokinetic interactions between these two classes of drugs have been described in experimental models, and exceptionally in humans. The aim of the present investigation was to study the interactions of these two drugs with three antibiotics (amoxicillin 500 mg x 2, cefadroxil 500 mg x 2, cefixime 200 mg and one placebo capsule) on pharmacodynamic parameters and on rate of killing in the serum of six healthy volunteers receiving the antibiotic associated or not with the product in a randomized cross-over double-blind trial. The bacteria most often involved in sinusitis, bronchitis and otitis media (Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus) three target diseases for oral cephalosporins and amoxicillin, were chosen for bacteriological study. Blood samples were obtained at 0.25, 0.50, 1, 1.5, 2, 4, 6 and 12 h after oral administration of antibiotics alone or associated with the drugs. There was a wash-out period of at least 1 week between the eleven sequences. Antibiotics were measured by two methods: bioassay and high performance liquid chromatography (HPLC). All serum samples obtained at peak level, 4 and 6 h were tested for killing rate. Area under the time kill curve was calculated by the trapezoidal rule method and relative bioactivity in percent was defined as follows: (AUC control - AUC test)/AUC control x 100. No pharmacokinetic interaction was found in the AUC and T1/2 of the plasma concentrations of the antibiotics or associated with the drugs, regardless of dose, as determined by HPLC or microbiological assay. For these beta-lactam antibiotics killing rate was found to be time-dependent. Bactericidal activity was improved on H. influenzae when cefixime was associated with niflumic acid and became concentration-dependent. A significant concentration relation was also found with niflumic acid or paracetamol associated with cefixime on Strep. pneumoniae.

Acetaminophen↗

[Pharmacology of recombinant cytokines].

The explosive growth in cytokines has been followed by many attempts to bring them into clinical use. Immediate applications are already recognized in cancer and infectious diseases. Future applications are foreseeable in inflammatory and auto-immune diseases. The use of accurate and sensitive methods for cytokine measurements in body fluids is an absolute prerequisite to define the pharmacological effect of parenterally administered recombinant cytokines. Enzyme-linked immunosorbent assay (ELISA) has become the most convenient method but there is an urgent need for a real standardization of this technique. Moreover, ELISA may be susceptible to cross-reactivity due to the high percentage of amino-acid homology between the various cytokines. The pharmacokinetic profile of recombinant cytokines may be influenced by endogenous production, receptor binding effect, receptor antagonists and soluble receptors. Cytokines elicit an immunogenic response and anticytokine antibodies should be monitored. Serum half-life of elimination is about 4 h after subcutaneous administration. In contrast with conventional drugs, pharmacokinetic data do not provide useful information for the design of a clinical protocol, and the rational choice of the unit dose and dosing schedule should be based on biological considerations. In vitro studies on the duration of receptor occupancy required for effector augmentation provide one of the bases for the choice of therapeutic protocol. Recombinant cytokines share biological activities and synergize with or antagonize one another so that it is difficult to evaluate their effects in clinical studies. Thus, pharmacological results do not always correlate with therapeutic effect. There is no direct relationship between dose and activity. One must determine the optimum biological dose (OBD), which is the minimal dose resulting in a significant augmentation of effector cell activity correlating with the therapeutic response. Surrogate markers may help to assess the clinical response such as 2',5'-oligo(A) synthetase or neopterin following interferon administration. Cytokines' adverse effects are difficult to foresee in the human because studies in rodents and dogs cannot fully predict them because of their species specificity. New relevant animal models are needed such as transgenic animals and parallel animal models. Pro-inflammatory cytokines inhibit cytochrome P-450 and have the potential to cause drug-cytokine interactions.

Animals↗

[Antibacterial activity of urine after administration of ofloxacin for 5 days].

The antibacterial activity of ofloxacin was evaluated in urine over a period of 96 h after oral administration for 5 days of 200 mg twice a day in 12 healthy female volunteers. Bacteriostatic and bactericidal activity of urines were studied for five strains of enterobacterias recovered from urinary infections: two strains of Escherichia Coli Nal-S and Nal-R, two strains of Proteus mirabilis Nal-S and Nal-R, and one strain of Klebsiella pneumoniae Nal-S. Mean urinary concentrations of ofloxacin were very high during the first 12 h following last intake. They were still above 7 mg/l till the 48th hour and above 1.6 mg/l till the 72nd hour. Bactericidal activity of urine was present for 72 h in respect of four strains studied at that time; urine was not bactericidal as regards E. coli Nal-R. After 5 days of oral treatment with ofloxacin (200 mg b.i.d.), urine retains a bactericidal activity for at least 72 h against bacterial strains of urinary tract infections.

Anti-Infective Agents, Urinary↗

[Bismuth revisited in Helicobacter pylori gastro-duodenal infection].

The various hypothesis for the explantation of reversible bismuth encephalopathy are reviewed and discussed. Today, this side effect appears to be devoid of mystery, due to uncontrolled and inhibited ingestion of bismuth salts which increased the emergence of genetic and physiopathologic risk factors and brought about the cases of neurotoxicity. Bismuth therapy has shown major efficacy in the treatment of gastroduodenal ulcers. Colloidal bismuth subcitrate is as effective as the H2-receptor antagonists in peptic ulcer. In addition, it offers a lower rate of relapse. This therapeutic benefit has been attributed to a cytoprotective and demulcent action. Moreover bismuth acts as an antimicrobial agent, suppressing the organism Helicobacter pylori which occupies a central place in contemporary views on pathophysiology of ulcer disease. Side effects so far reported have been very infrequent mild and transient when the drug is used at low dosage providing blood-bismuth concentration above toxic values. Colloidal bismuth subcitrate complies to the requirements for a modern drug insofar as it is prescribed in period no longer than 6-8 weeks, followed by 8 weeks bismuth-free intervals.

Bismuth↗

[Aggregation of macrophages by a human lymphokine (MAgF). Role of the eicosanoid system].

Peritoneal exudate cells aggregate when exposed to the lymphokine Macrophage Aggregating Factor (MAgF). The role of prostaglandins in the aggregation of these cells has been investigated with a quantitative assay. Results are discussed in the context of the mode of action of the migration inhibiting factor (MIF) and of the other non immune aggregating stimuli such as C5a and fMLP. Prostaglandins E1, E2, and F2 alpha alone did not cause aggregation of macrophages but partially inhibited the MAgF aggregation of macrophages and this effect was not different from the one obtained with MAgF. MAgF, calcium ionophore A23187 and arachidonic acid induced aggregation were blocked by 5, 8, 11, 14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism, by indomethacin (10(-4), 10(-6) M) by corticosteroids (dexamethazone, methylprednisolone, hydrocortisone) but not by aspirin (10(-2), 10(-4) M) nor by phenylbutazone (10(-4), 10(-5) M). These results suggest a causal relationship between MAgF induced macrophage aggregation and that due to other stimuli with respect to the derivatives of arachidonic acid. The lipoxygenase pathways metabolites stimulate aggregation whereas the cyclo-oxygenase pathways metabolites inhibit it.

Anti-Inflammatory Agents↗