Infectious diarrhoeas: weakening of mucosa protection induced in rabbit ileal loops by a pathogenic Escherichia coli.

The histological, enzymatic, and electrolyte changes induced by a toxigenic strain of E. coli (0128B12) were studied in the rabbit. After 4 hours of contact with the bacteria, one-third of the goblet cells of the intestinal epithelium were totally degranulated, indicating an increase in the destruction of mucus and hence a weakening of mucosal protection through action of bacterial enzymes. The good histological conservation of the ileal mucosa at the end of the study period was confirmed by the stability of the disaccharidase of the glycocalyx and of the luminal surface membrane enzymes, alkaline phosphatase and leucine amino-peptidase. The observed water, sodium and bicarbonate losses were principally due to the action of the bacterial toxins on the ionic pumps of the epithelial cells.

A histological, enzymatic and water-electrolyte study of the action of smectite, a mucoprotective clay, on experimental infectious diarrhoea in the rabbit.

The histological, enzymatic and water-electrolyte modifications induced by the administration of smectite, a type of clay reputed to be mucoprotective, have been studied in the rabbit ileal mucosa during infection by saprophytic bacteria and toxigenic E. coli 0128B12. Smectite diminished the bacterial mucolysis and the destruction of the luminal surface membranes of the intestinal epithelium by pathogenic bacteria, as evidenced by the elevation of the disaccharidase and alkaline phosphatase levels. As a result of these effects, the net ion fluxes and net fluid changes favour absorption. These results could account for the mechanism of action of smectite in infectious human diarrhoea.

Influence of coadministration of fluoxetine on cisapride pharmacokinetics and QTc intervals in healthy volunteers.

STUDY OBJECTIVE: To evaluate the effect of fluoxetine on the pharmacokinetics and cardiovascular safety of cisapride at steady state in healthy men. DESIGN: Open-label, three-phase, sequential study. SETTING: Clinical research center. SUBJECTS: Twelve healthy male volunteers. INTERVENTIONS: Each subject was treated according to the following sequence: baseline; phase 1 (days 1-6): cisapride 10 mg 4 times/day; washout (days 7-13); phase 2 (days 14-44): fluoxetine 20 mg/day; and phase 3 (days 45-52): cisapride 10 mg 4 times/day (days 45-51) plus fluoxetine 20 mg/day (days 45-52). MEASUREMENTS AND MAIN RESULTS: Blood samples were drawn and 12-lead electrocardiograms performed at specified time points after the last morning dose of cisapride in phases 1 and 3. Blood samples also were taken before morning doses on the 3rd, 4th, and 5th days of phases 1 and 3. Electrocardiograms were done at baseline and on the last day of the washout period and phase 2. Coadministration of fluoxetine significantly decreased cisapride plasma concentrations. There were no clinically significant changes in corrected QT intervals during administration of cisapride alone or with fluoxetine. Cisapride was well tolerated when administered alone or with fluoxetine. CONCLUSION: Cisapride can be administered safely to patients receiving low therapeutic dosages of fluoxetine.

An attempt to use artificial membranes to investigate cellular membrane permeation--application to nitroglycerin and isosorbide dinitrate.

The pharmacodynamic efficiency of nitroglycerin (TNG) is 3 to 4 times higher than that of isosorbide dinitrate (ISDN). In a previous work the authors have shown that this difference is partially due to the transmembrane diffusion potential of the molecules. The aim of this present study is to confirm this hypothesis by using artificial solid lipid membranes and thus to validate the method which will be used to predict the transmembrane diffusion of drugs. Two types of artificial membranes, having nearly the same liposolvent properties as the biological membrane, are tested to investigate intracellular drug penetration. These artificial membranes are fitted on the Dibbern's three phases apparatus: the Resomat 2. The results are in accordance with the data obtained on erythrocyte membranes showing that both drugs have a good transmembrane diffusibility and also that TNG presents a quicker intracellular penetration than ISDN. These results contribute to validate this method, using artificial membranes, to predict the intracellular penetration of molecules.

[Cytological study of the mode of contraceptive action of nonoxynol-9]. / Etude cytologique du mode d'action contraceptive du nonoxynol-9.

PIP: Vaginal spermicides, which were made of many different compounds prior to the 1960s, are today based on a few active principles only. Nonoxynol 9 is the most widely used of these safe and effective surfactants. Methods of evaluation of spermicides are all based on measurement of the time and dose levels necessary to achieve immobilization of sperm under specific conditions. Studies of the mode of action of nonoxynol 9 suggest that the spermicide causes major alterations of the surface membranes and in the organites. To determine whether nonoxynol 9 merely immobilizes or also kills sperm, specimens were collected from 21 donors after 3-5 days of abstinence. The sperm sample characteristics were compared with those of men of proven fertility to ensure that the sperm had fertile characteristics. 8 of the 21 donors were of proven fertility. Criteria for judging the effect of nonoxynol 9 included sperm mobility before and after nonoxynol 9 administration and percentage of live sperm before and after nonoxynol 9 administration. The technique for demonstrating whether sperm are still alive after coming in contact with nonoxynol 9 requires about 30 seconds to 1 minute for completion, so it cannot be stated that immobilization and death of the sperm are instantaneous. The quantities of nonoxynol 9 used were about 1/10 of those used in spermicide contraceptives. The dosage corresponded to about 10 mg of nonoxynol 9 for an ejaculate, while those of local contraceptives are usually 100 mg. This work demonstrated that the action of nonoxynol 9 was not limited to simple immobilization of sperm, but also involved killing them. The advice to spermicide users to avoid vaginal cleansing for several hours after intercourse should be reevaluated in light of these findings.^ieng

[Transmembrane passage of trinitrine and isosorbide dinitrate. Study of natural membranes]. / Etude du passage transmembranaire de la trinitrine et du dinitrate d'isosorbide. Etude sur membrane naturelle.

Nitroglycerin pharmacodynamic efficiency is 3 to 4 times higher than isosorbide dinitrate efficiency. Authors put forward that this difference is at least partially pertained to the transmembrane diffusion potential of the molecules. Data of this first study on red cell membranes are in accordance with this hypothesis.

[The transmembrane diffusion of trinitrine and isosorbide dinitrate. Study of artificial membranes]. / Etude du passage transmembranaire de la trinitrine et du dinitrate d'isosorbide. Etude sur membrane artificielle.

Nitroglycerin pharmacodynamic efficiency is 3 to 4 times higher than isosorbide dinitrate efficiency. Data of this study on physiological and artificial membranes point the greater nitroglycerin transmembrane diffusion, which is discussed as a possible relevant explanation.

[Infectious diarrhea: weakening of mucosal protection caused by a pathogenic Escherichia coli in ileal loops in the rabbit]. / Diarrhées infectieuses : affaiblissement de la protection muqueuse induite par un Escherichia coli pathogène au niveau des anses iléales de lapin.

The histological, enzymatic and water-electrolyte modifications induced by a toxinogenic strain of E. coli (O128B12) were studied. The observed water loss was due to the action of the bacterial toxins on the ionic pumps of the epithelial cells. After 4 hours of contact with the bacterial strain, one-third of the goblet cells of the intestinal epithelium were totally degranulated. This indicated an increase in the destruction of the mucus and therefore the weakening of mucosa protection through action of bacterial enzymes and toxins.