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Biomedical subjects

M Duval

Publications and source records attributed to M Duval.

90 records · Page 5Linked to original sources

Investigation of drug absorption from the gastrointestinal tract of man. IV. Influence of food and digestive secretions on metoprolol jejunal absorption.

The influence of nutrients and digestive secretions on the intestinal absorption and bioavailability of the beta-adrenoceptor antagonist, metoprolol, was investigated in an isolated segment of jejunum using an intestinal perfusion technique. Two solutions containing metoprolol, one with, and one without nutrients, were perfused into the jejunum with an occluding balloon inflated or deflated. Jejunal fluid, blood and urine samples were then collected for drug or metabolite estimation. In the segment studied, metoprolol absorption from the nutrient solution was four times that observed during perfusion of the saline solution. Bile salts did not enhance drug absorption. Both in the presence and absence of nutrients, a linear relationship was observed between the computed cumulative amount of drug absorbed from the gastrointestinal tract and the resulting plasma concentration at each sampling time, indicating that first-pass loss was not saturated. This result was also reflected in the similarity of the AUC:dose ratios, and in the lack of effect of nutrients on the metabolism of the drug.

Adult↗

Studies on fibronectin in inflammatory vs non-inflammatory polymorphonuclear leucocytes of patients with rheumatoid arthritis. I. Immunofluorescent and flow cytometric analysis.

Using indirect immunofluorescence and flow cytometry, we studied the reactivity of an antibody to human fibronectin with human polymorphonuclear leucocytes (PMNL). Our main objective was to compare the intensity of reaction of this antibody with inflammatory vs non-inflammatory PMNL. We used peripheral blood PMNL as a source of non-inflammatory cells and PMNL isolated from the synovial fluid of patients with rheumatoid arthritis as a source of inflammatory cells. Our findings revealed considerably brighter staining of the inflammatory PMNL. Using flow cytometry as a method of measurement, a difference in fluorescence intensity of at least 40 channels (log scale) was observed in all 12 patients studied when comparing peripheral blood with synovial fluid PMNL. In inflammatory PMNL, fibronectin was found both at the intracellular and membrane levels of the cell whereas fibronectin could be detected only intracellularly in non-inflammatory PMNL.

Antibodies, Anti-Idiotypic↗

Ecological distribution of Legionellaceae in the Quebec city area.

One hundred environmental water samples, which were collected in the Quebec city area and cultured on buffered charcoal yeast extract medium and three selective media, were inoculated to guinea pigs and were screened by direct immunofluorescent staining (DFA) for the presence of Legionellaceae. Six isolates were made (four Legionella pneumophila and two Tatlockia (Legionella) micdadei: three by animal inoculation and three by culture). No samples were simultaneously positive by both methods. After screening by DFA, 43 of the 100 samples were positive for Legionellaceae and 27 of those contained more than one serogroup and (or) species of Legionellaceae. Legionella pneumophila (serogroups 1 to 6) was the most frequent species seen by DFA. These results clearly show that Legionellaceae are frequent members of the freshwater microbial flora of the Quebec city area.

Culture Media↗

Serum somatomedin activity measured as sulphation factor in peripheral, hepatic and renal veins of mongrel dogs: basal levels.

Serum somatomedin (SM) activity measured as sulphation factor on chick embryo cartilage was determined in peripheral (PV), hepatic (HV) and renal (RV) veins or 36 mongrel dogs. Mean SM activity +/- SEM was 0.53 +/- 0.03 U/ml in peripheral and hepatic veins, and 0.61 +/- 0.04 U/ml in renal vein (P less than 0.005). When the gradient of SM activity in hepatic or renal vein to that in peripheral vein, [HV]-[PV] or [HV]-[PV], was plotted versus SM activity in peripheral blood [PV], a negative correlation was found in the case of hepatic but not of renal blood. These data indicate that the kidney may be a production site of SM activity, whereas the liver is differently implicated in the overall regulation of SM activity.

Animals↗

Serum somatomedin activity measured as sulphation factor in peripheral, hepatic and renal veins in normal mongrel dogs: Early effects of intravenous injection of growth hormone.

The aim of this work was to study the early effects of an intravenous growth hormone (GH) injection on serum somatomedin (SM) activity in samples from peripheral (PV), hepatic (HV) and renal (RV) veins in dogs: 5 dogs were given one bovine growth hormone (bGH) injection, 1 dog was given 5 different doses of human growth hormone (hGH) and 6 control dogs were given saline. In bGH-treated dogs, a significant increase of SM activity occurred in the three vessels without difference between vessels. An early paradoxical decrease of serum somatomedin activity appeared in the dogs given more than 1.15 IU/kg. In the dog given hGH, the response of SM activity was significantly related to the hGH dose in the PV and not in the other vessels. These data seem to indicate that other sites than the liver and the kidney are involved in the production of GH-induced serum somatomedin activity. Following GH injection as well as in basal status, the liver may be implicated in the regulation of serum somatomedin activity.

Animals↗

Chronic administration of chenodeoxycholic acid increases cholesterol saturation in bile in the dog.

Six dogs were given chenodeoxycholic acid, 200 mg/day for 15 days; gallbladder and hepatic bile samples were taken and biliary bile acids, phospholipids and cholesterol were compared to those of fourteen control dogs. It was found that: (1) the cholesterol saturation index of gallbladder bile was higher in treated dogs (0.12 +/- 0.06; m +/- SD) than in controls (0.07 +/- 0.01; P less than 0.05); the proportion of chenodeoxycholic acid in gallbladder bile was higher in treated dogs (27.8 +/- 12.5%) than in controls (4.5 +/- 1.9%; P less than 0.01); (2) in hepatic bile, the saturation index and proportion of chenodeoxycholic acid were significantly higher in treated dogs (respectively 0.13 +/- 0.03 and 21.6 +/- 8.8%) than in control dogs (respectively 0.07 +/- 0.01; P less than 0.01 and 4.6 +/- 2.2%; P less than 0.01). In the dog, chronic administration of chenodeoxycholic acid increases cholesterol saturation in bile. It is concluded that the difference of effect of chenodeoxycholic acid in man and in the dog is not related to the duration of administration, but to a species difference.

Administration, Oral↗

Effect of lysine acetylsalicylate on biliary lipid secretion in dogs.

1. The influence of lysine acetylsalicylate on bile flow, erythritol clearance and bile salt, phospholipid and cholesterol secretion in bile was studied in unanaesthetized dogs fitted with a Thomas duodenal cannula. 2. Lysine acetylsalicylate induced a marked increase in bile flow and a parallel increase in erythritol clearance although the bile salt secretion remained unchanged; this suggests that the compound stimulated the formation of the canalicular (hepatocytic) bile salt-independent fraction of bile flow. 3. Lysine acetylsalicylate induced a significant decrease in biliary phospholipid and cholesterol secretion and the cholesterol saturation of bile was significantly reduced. 4. It is postulated that the decrease in phospholipid and cholesterol secretion resulted from the dilution of intracanalicular bile salts. This effect of lysine acetylsalicylate, and possibly of other bile salt-independent choleretics, may be of value in the treatment of cholesterol gallstones in man.

Animals↗

Influence of dehydrocholate and taurocholate on bromsulphthalein uptake, storage, and excretion in the dog.

The influence of dehydrocholate on bromsulphtalein relative-storage capacity, bilary transport maximum (Tm), and fractional transfer rates between plasma, liver and bile have been studied in unanaesthetized dogs. In six dogs, storage capacity, Tm, and fractional transfer rates from plasma to liver, liver to bile, and liver to plasma were measured during 0-15 M NaCL infusion and the measurements were repeated under a dehydrocholate infusion of 95 mumol. min-1, ie, an infusion rate approaching the known biliary Tm of bile salts. It was found that: (a) storage capacity and fractional transfer rates from plasma to liver significantly lower during dehydrocholate infusions (respectively 18-0 plus or minus SD 9-0 mg-mg-1. 100 ml-1 and 0-120 plus or minus SD 0-035 min-1) than during NaCL infusions (respectively 47-0 plus or minus 21-0 mg. mg-1. 100 ml-1 and 0-280 plus or minus SD 0-055 min-1; P smaller than 0-001); (b) Tm and fractional transfer rates from liver to bile were also significantly lower during dehydrocholate infusion (respectively 3-2 plus or minus SD 1-1 mg. min-1 and 0-013 plus or minus SD 0-004 min-1) than during NaCl infusion (4-8 plus or minus SD 1-1 mg. min-1 and 0-033 plus or minus SD 0-017 min-1; P smaller than 0-02); (c) in three additional experiments, taurocholate had similar effects on storage capacity and Tm. These findings suggest that competition occurred between bile salts and bromsulphthalein for hepaticuptake and storage. They support the hypothesis that the decreased disappearance rate and relative storage capacity of bromsulphtalein observed during biliary obstruction may be due to competition between bile salts and bromsulphthalein for hepatic uptake and storage.

Animals↗

Hepatocellular uptake of erythritol and mannitol in the dog.

The purpose of this study was to determine the initial space of distribution of [14C]erythritol (mol wt 122) and [14C]mannitol (mol wt 182) in the liver of the dog by the single-injection, multiple-indicator-dilution method. 22Na was used as the extracellular indicator and tritiated water (THO) was used as total liver water indicator. The indicators were simultaneously injected into the portal vein of anesthetized dogs and dilution curves were obtained at the outflow from the hepatic vein. It was found that hepatic venous dilution curves of [14C]erythritol and THO were practically identical in all experiments. In contrast, the dilution curves of [14C]mannitol were generally distinct from those of THO. Analysis of [14C]mannitol-dilution curves according to Goresky suggested that the observed difference between this solute and THO was the result of a limited permeability of the sinusoidal membrane to mannitol. It is concluded that [14C]erythritol has instantaneous and practically unrestricted access to total liver water. This finding supports the validity of using erythritol as a liver cell water marker. A larger solute, [14C]mannitol, has restricted access to total liver cell water because of a permeability barrier in the sinusoidal liver cell membrane, but its diffusion into the hepatocyte is also very rapid.

Animals↗

Hepatocellular uptake of bile acids in the dog: Evidence for a common carrier-mediated transport system. An indicator dilution study.

The purpose of this study was to compare the uptake of taurocholate (TC) by the liver of the dog to that of taurochenodeoxycholate (TCDC) and to examine the influence of TCDC on TC uptake. The uptake of these bile acids by the liver of the intact was studied with the multiple indicator dilution method, using 51Cr-labeled red blood cells as a vascular indicator, 125I-labeled albumin as an extravascular reference, and one or two labeled bile acids. The analysis of the dilution curves fitted well a three-compartment model, and no return of the extracted bile acids to the extracellular space could be detected. The initial space of distributin of TC in the presence of a fixed dose of TCDC was 1.25 +/- 0.09 (SD) times greater than that of albumin. Analysis of the data for TC uptake in the presence of TCDC was consistent with Michaelis-Menten kinetics, as previously established for TC alone. The calculated initial maximal velocity of uptake (Vmax) of TC in the precence of TCDC was 4.92 +/- 1.36 (SD) mumoles per sec per 100 g of liver. This value is not significantly different from the Vmax previously calculated for TC alone. The apparent KD (dose of TC yielding half-maximal velocity) was 18.10 +/- 6.14 (SD) mumoles per 100 g of liver, a value significantly higher than that obtained in the absence of TCDC. A K1 (the Michaelis-type constant characterizing the inhibition of TC uptake by TCDC) of 2.71 +/- 1.08 (SD) mumoles of TCDC per 100 g of liver was calculated. These observations are consistent with competitive inhibition of TC uptake by TCDC, and thus with the existence of a common carrier-mediated transport system for TC and TCDC. Estimation of the kinetic characteristics of the two bile acids from dilution curves obtained simultaneously showed that the affinity for the carrier was higher for TCDC than for TC, but that the maximal capacity was lower for TCDC than for TC.

Animals↗

Purification of developmentally regulated avian 400-kDa intermediate filament associated protein. Molecular interactions with intermediate filament proteins and other cytoskeleton components.

IFAPa-400, a 400-kDa developmentally regulated protein thought to be associated with intermediate filaments, has been purified from chick embryo hearts to investigate its interaction with vimentin and other IF proteins and to identify other cellular components to which this cytoskeletal protein associates. Previous studies suggested that this protein was associated with the vimentin-containing intermediate filament lattice of myoblasts and neuroblasts before their terminal differentiation, providing these cells with a particular intermediate filament cytoskeleton that could satisfy specific mechanical requirements during their intense morphogenetic activities. Although IFAPa-400 partially reassociated with vimentin and desmin in disassembly-reassembly experiments using crude IF preparations from chick embryo hearts, in vitro recombination of purified IFAPa-400 with vimentin and desmin failed to demonstrate any direct association. When purified IFAPa-400 was used as a probe in blot overlay assays, however, specific binding to vimentin and desmin was observed, providing the first evidence of a physical association between IFAPa-400 and intermediate filament proteins. The blot overlay experiments also demonstrated that IFAPa-400 binds to two unidentified polypeptides of 19 and 32 kDa. These results are thus consistent with the hypothesis that a structural lattice requiring a vimentin-IFAPa-400 combination constitutes the intermediate filament system of myogenic and neurogenic cells.

Animals↗