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Biomedical subjects

H Carlier

Publications and source records attributed to H Carlier.

At least 19 recordsLinked to original sources
PubMed2001

Prednisolone does not prevent hypersensitivity reactions in antiretroviral drug regimens containing abacavir with or without nevirapine.

OBJECTIVES: To determine the effect of adjuvant prednisolone use on the development of abacavir (ABC)- and nevirapine (NVP)-associated hypersensitivity reactions (HSR). METHODS: Randomized open-label study in antiretroviral-naive adult HIV-1 infected patients using a factorial design in which NVP and/or hydroxyurea (HU) and/or prednisolone are added to a regimen of ABC, zidovudine and lamivudine. Prednisolone (40 mg once daily) was added for the first 2 weeks of treatment. As it was difficult to distinguish ABC-associated HSR from NVP-associated HSR, these events were treated as a composite endpoint. The odds ratio (OR) of developing HSR for prednisolone-use was calculated with and without stratification by NVP and/or HU. Logistic regression was performed to identify risk factors for developing HSR. RESULTS: Of the 229 patients 115 were randomized to prednisolone and 114 to no-prednisolone; 19 (17%) and 11 (10%) patients, respectively, developed HSR. The expected prevention of HSR by prednisolone use was not observed. In fact use of prednisolone showed an increased risk for HSR although this did not reach statistical significance [OR, 1.82; 95% confidence interval (CI), 0.82-4.03]. There was a higher incidence of HSR in the NVP group than in the non-NVP group (20% versus 6%; P = 0.002). An additional risk factor identified in a multivariate logistic model was a high baseline CD4 cell count (OR, 1.26 per 100 x 10(6) cells/l increase; 95% CI, 1.06-1.51). CONCLUSIONS: The simultaneous start of ABC and NVP in first-line antiretroviral regimens should be avoided because of a high (20%) incidence of HSR. Short-term therapy with prednisolone did not prevent HSR in patients using ABC with or without NVP.

Adult↗
PubMed2001

The steady-state pharmacokinetics of efavirenz and nevirapine when used in combination in human immunodeficiency virus type 1-infected persons.

The steady-state pharmacokinetics of efavirenz and nevirapine, when used in combination to treat human immunodeficiency virus type 1 (HIV-1)-infected subjects, were investigated. HIV-1-infected persons who had used efavirenz (600 mg once daily) for > or =2 weeks were eligible for study inclusion. The plasma pharmacokinetics of efavirenz were determined over 24 h. Subsequently, nevirapine (400 mg once daily) was added to the regimen. After 4 weeks, the pharmacokinetics of efavirenz and nevirapine were assessed over 24 h. The differences between the pharmacokinetic parameters of efavirenz with and without nevirapine were analyzed, and the pharmacokinetics of nevirapine were compared with those in historical control patients. The exposure to efavirenz when combined with nevirapine was significantly decreased by 22% (area under the plasma concentration vs. time curve), 36% (minimum plasma concentration), and 17% (maximum plasma concentration). Nevirapine pharmacokinetics appear to be unaffected by coadministration of efavirenz, compared with data from historical control patients.

Adult↗
PubMed1996

Partition of oleic acid between the lymph and portal blood in rats having a diverted bile-pancreatic duct.

The present study examines the suggestion that in the absence of adequate bile and pancreatic juice, which support the absorption from the gut of long-chain fatty acids into lymph, the fatty acids are absorbed directly into the portal blood. Oleic acid (18:1) partitioning between lymph and portal blood was investigated in intact and bile- and pancreatic juice-diverted rats. In a first set of experiments, 18:1 absorption from the gut into lymph and blood was studied by continuous recovery of the mesenteric lymph for 6 h and mesenteric portal venous blood for 1 h. In a second set of experiments, esterification processes were investigated by study of the mucosal distribution of labelled lipids and by mono- and diacylglycerol acyltransferase (EC 2.3.1.22 and EC 2.3.1.20 respectively) specific activities. In the bile- and pancreatic juice-diverted rats the absorption of labelled 18:1 into lymph was significantly reduced during the first 3 h of intraluminal infusion of this substrate. In such rats a compensatory absorption of labelled 18:1 into mesenteric portal blood was not observed. At 6 h after micellar lipid-mixture infusion, the overload of lipids both in free form and as triacylglycerols persisting in the mucosa paralleled the lower acyltransferase specific activities observed in bile- and pancreatic juice-diverted rats. These studies demonstrate the absence of a previously proposed compensatory absorption of 18:1 into portal blood when absorption into lymph is impaired by an inadequate supply of bile and pancreatic juice.

Animals↗
PubMed1995

Expression of fatty acid binding protein in the liver during pregnancy and lactation in the rat.

Expression of the liver fatty acid binding protein (L-FABP) has been studied in the liver of pregnant and lactating rats. The L-FABP concentration found in the cytosol by immuno-enzymatic assay (ELISA) was consistently higher in the dams during the pregnancy and the lactation than in the age-matched virgin females. Paradoxically, a decrease in the L-FABP mRNA level occurred in the maternal liver during the last days of the gestation. This level remained low on days 7 and 14 of the lactation. Since the transcription rate of the L-FABP gene was unchanged in the maternal liver, these data suggest a post-transcriptional regulation of the L-FABP during pregnancy and lactation in the rat. The nutritional adaptations occurring during pregnancy and lactation are not involved in this regulation since a chronic maternal food-restriction failed to correct these modifications. The mechanism of this regulation is presently unknown, but possibilities include hormonally mediated effects.

Animals↗
PubMed1995

Evidence for transcriptional induction of the liver fatty-acid-binding-protein gene by bezafibrate in the small intestine.

The effect of bezafibrate on cytosolic fatty-acid-binding-protein (FABPc) production along the small intestine has been investigated in mice. This drug increased the intestinal fatty-acid-binding-protein (I-FABPc) and liver fatty-acid-binding-protein (L-FABPc) mRNA levels in the duodenum. The extents of induction in the duodenum and in the liver are similar. However, the degree of stimulation gradually decreases along the length of the gut, no effect being found in the ileum. An efficient absorption of this drug as early as the proximal part of the small intestine may explain this phenomenon. The L-FABPc gene is silent in terminal ileum of mice, but a direct infusion of bezafibrate into the ileum switches it on. We used this original model to follow the time course of induction of the L-FABPc gene by bezafibrate. L-FABPc mRNA was first detected 4 h after fibrate infusion, reached a maximum level at 16 h and subsequently decreased at 24 h. This induction was totally blocked by cycloheximide. Sunflower oil also caused small increases in the L-FABPc mRNA levels. The transcriptional origin of the induction triggered both by bezafibrate and sunflower oil was demonstrated by run-on assays. These data indicate that (a) the transcription of the L-FABPc gene is induced by bezafibrate via de novo protein synthesis and (b) components of sunflower oil can transcriptionally activate the L-FABPc gene. Our results also demonstrate that the mouse terminal ileum is a useful system for studying the regulation of L-FABPc gene expression both in vivo and in vitro.

Animals↗
PubMed1994

Incorporation of exogenous unsaturated fatty acids in mouse jejunal explants.

Esterification processes of oleic (OA), linoleic (LA) and arachidonic acids (AA) were investigated in mouse jejunal explants with some references to age (2.5, 12 and 21 months) of the animal tissue donors. Explants were incubated either for 15 min in a stirred medium enriched with lipids or cultured for 15 min in Falcon dishes in a culture medium enriched with lipids, then for 6 h in a lipid-free medium. In 2.5-month-old mice, released lipoprotein OA secreted in the medium was especially integrated into the triacylglycerols, while LA was significantly integrated into glycerophospholipids. Triacylglycerol formation from released AA was always significantly lower than from OA. With increasing age of the animals, decreasing amounts of OA appeared in triacylglycerols. The preferential association of OA with triacylglycerols observed in jejunal explants coincided with a preferential esterification of OA observed with the enzymatic assays. The utilization of the arachidonoyl-coenzyme A by the microsomal acyltransferase was low at all ages.

Acyltransferases↗
PubMed1993

Transcriptional induction of the fatty acid binding protein gene in mouse liver by bezafibrate.

The mechanism by which hypolipidemic peroxisome proliferators of the fibrate family induce the liver fatty acid binding protein in liver of rodents is unknown. In order to delineate the level at which this protein is induced, the transcriptional activity of the specific gene encoding for liver fatty acid binding protein was measured in isolated hepatocyte nuclei obtained from male Swiss mice daily force-fed during 7 days with 400 mg/kg body weight bezafibrate. This treatment induced a 4-fold increase in the liver fatty acid binding protein transcription rate. Liver fatty acid binding protein mRNA level, measured by Northern blot analysis and cytosolic content of this protein, analyzed by immunoblotting, increased concurrently. From these results we conclude that the increase in the cytosolic liver fatty acid binding protein level by bezafibrate is due to an enhancement of the transcription rate of the liver fatty acid binding protein gene. Whether the transcriptional effect is mediated by peroxisome proliferator-receptor remains to be elucidated.

Animals↗
PubMed1992

Diet fatty acid composition, age and rat jejunal microvillus enzyme activities.

1. Lactase, sucrase, maltase, trehalase and alkaline phosphatase activities of rat proximal jejunum were measured in 3, 6, 9, 12, 18 and 24-month-old rats fed with diets differing in their fatty acid composition. 2. A drop of 47-53% of the specific enzyme activity was observed with disaccharidases against a decrease of 71% for alkaline phosphatase in the 24-month-old rats compared to the 3-month-old rats. 3. Changes in dietary fatty acid composition, either in the saturated or monounsaturated ratio, or in the polyunsaturated fatty acid composition, did not significantly interfere with this aging effect.

Aging↗
PubMed1992

Administration modalities and intestinal lymph absorption of arachidonic acid in rats.

We investigated the effects of the proportion of arachidonic acid on lymph lipoprotein synthesis in rats, when infused in the presence of lipids with varying degrees of saturation. A single dose of 90 mumol of lipid was administered intraduodenally and intestinal lymph was collected. Emulsion lipid constituents were 90 mumol of [14C]arachidonic acid alone, or either 30 mumol of [14C]arachidonic acid or 5 mumol of [14C]arachidonic acid and 25 mumol of linoleic acid, with 30 mumol of a free fatty acid and 30 mumol of a monoglyceride (the more saturated: oleic acid + monopalmitin; the more unsaturated: linoleic acid + monoolein). Radioactive lymph recovery of [14C]arachidonic acid infused alone reached 32.6 +/- 1.3% of the radioactivity administered and the presence of another fatty acid and a monoglyceride increased it from 38.7 +/- 2.6 to 51.9 +/- 1.1%. For 30 mumol of arachidonic acid, integration into lymph phospholipids was higher when arachidonic acid was infused with oleic acid and monopalmitin than with linoleic acid and monoolein (7.3 +/- 2.7 and 2.8 +/- 0.2% at the absorption peaks, respectively), and it was 4.8 +/- 0.5% when arachidonic acid was infused alone. For 5 mumol of arachidonic acid, the degree of unsaturation of the added lipid did not modify phospholipid incorporation, which was maintained at 6.9 to 7.2%. The proportion and size of chylomicrons increased with the degree of lipid emulsion unsaturation. Percentages of [14C]phospholipids and of chylomicrons were highly correlated. The proportion of arachidonic acid and degree of lipid emulsion unsaturation affected lymphatic arachidonic acid absorption modalities.

Animals↗
PubMed1991

Digestion and absorption of polyunsaturated fatty acids.

Polyunsaturated fatty acids play an important part in the structure and function of cellular membranes and are precursors of lipid mediators which play a key role in cardiovascular and inflammatory diseases. Dietary sources of essential fatty acids are vegetable oils for either linoleic or alpha-linolenic acids, and sea fish oils for eicosapentaenoic and docosahexaenoic acids. Because of the specificity of the pancreatic lipid hydrolases, triglyceride fatty acid distribution is an essential parameter in the digestibility of fats. The efficiency of the intestinal uptake depends on the hydrolysis and especially on their micellarization. n-3 polyunsaturated fatty acid ethyl ester digestion is recognized to be impaired, but n-3 polyunsaturated fatty acid triglyceride hydrolysis remains a controversial point, and to some authors explains differences observed between vegetable and fish oil absorption. So additional studies are required to investigate this intestinal step. In enterocytes, morphological and biochemical absorption processes involve reesterification of long-chain fatty acids and lipoprotein formation. At this level, specific affinity of I- and L-FABPc (cytosolic fatty acid binding proteins) to polyunsaturated fatty acids requires further investigation. A better understanding of the role of these FABPc might bring to light the esterification step, particularly the integration of polyunsaturated fatty acids into phospholipids. With reference to differences published between fish and vegetable oil absorption, longer-term absorption studies appear essential to some authors. Polyunsaturated fatty acid absorption is thought to be not very dissimilar to that of long-chain mono-unsaturated fatty acid absorption. However, several digestion and absorption specific steps are worth studying with reference to the crucial role of polyunsaturated fatty acids in the organism, and for example adaptation of possible dietary supplements.

Dietary Fats, Unsaturated↗
PubMed1991

Absorption and intestinal catabolism of fatty acids in the rat: effect of chain length and unsaturation.

Simultaneous portal blood absorption and intestinal mucosal catabolism of labelled fatty acids were investigated. Anaesthetized adult Wistar rats were infused intraduodenally either with 90 mumol of capric (C10:0), oleic (C18:1), linoleic (C18:2) or arachidonic (C20:4) 1-14C acids or with 30 mumol of each labelled fatty acid in addition to 30 mumol of oleic acid and 30 mumol of monopalmitin. For mixed infusates, experiments were carried out with two additional long-chain fatty acids: palmitic (C16:0) and erucic (C22:1) 1-14C acids. Radioactivity was quantified in the lipids and in the catabolic products in portal blood recovered at 5 min intervals for 1 h after infusion. At the end of the experiment, the disappearance of radioactivity from the mucosa was quantified. When labelled fatty acids were infused alone, 49% of the radiolabelled lipid disappearing from the mucosa was recovered in the blood for C10:0, but only 7.8% for C18:1, 6.4% for C18:2 and 10.6% for C20:4. With mixed infusates, 41% of the radiolabelled lipid disappearing from the mucosa was recovered in the blood for C10:0 compared with 12% for C18:1, 10.2% for C18:2, 10.5% for C20:4 and 2.7% for C16:0 and 2% for C22:1. Labelled catabolites appear with the same profiles as those of the respective fatty acids in blood. These studies confirm a minor absorption into blood of long-chain fatty acids compared to the medium-chain fatty acids and highlight differences in the catabolism of the fatty acids according to their chain length and their degree of unsaturation. The differences might be related to the differences in the fatty acid hydrosolubility and to their different affinities for the I- and L-cytosolic fatty acid binding proteins. These phenomena may be important in nutrition in relation to the availability of essential fatty acids.

Absorption↗
PubMed1991

Linoleic acid chyloportal partition and metabolism during its intestinal absorption.

1-14C linoleic acid intestinal absorption and simultaneous biochemical events were followed up on rats under vascular perfusion and on main mesenteric lymphatic duct fistulated rats. 1-14C linoleic acid was introduced in the duodenum alone in doses from 1.2 to 90 mumol or in the presence of oleic acid and monopalmitin (30/30/30 mumol/mumol/mumol). Mesenteric portal venous blood and chyle, respectively, were collected continuously for 1 and 6 h after the infusions. Blood-labeled lipid recovery varied from 4.7 to 2.2% of the 14C linoleic acid infused as the 14C linoleic acid dose infused increased, and dropped to 1.8% with the mixed lipid infusate. Lymph-labeled lipid recovery increased from 25.7 to 31.8% of the 14C linoleic acid infused as the dose infused increased, and rose to 48.1% with the mixed lipid infusate. The oxidation of 1-14C linoleic acid remained low: 0.8-3% of the infused radioactivity. A desaturation and elongation of 14C linoleic acid into 14C arachidonic acid was detected and discussed. We can conclude that the linoleic lymph absorption pathway remained preferential in our experimental conditions, simultaneous to a low rate of oxidation and an eventual ability for the enterocyte to convert this essential fatty acid arachidonic acid.

Animals↗
PubMed1991

[Quantification of mRNA coding for enterocyte fatty acid binding proteins (FABP) in rats: effect of high lipid diet and starvation].

We have tested in adult rat the specificity and the sensitivity of two cDNA probes derived from recombinant plasmids pJG19 and pJG418. The Northern blot analysis of total RNA extracted from small bowel reveals 0.9 and 0.7 kb mRNA corresponding respectively to the I and L-FABPc mRNA. A linear relation occurs between the amounts of input total RNA and the quantities of specific mRNA found by hybridization with cDNA probes (r = 0.991 and r = 0.998 for I and L-FABPc respectively). We have also evaluated the effect of drastic nutritional status: a high fat diet containing 45% of lipids and a starvation of three days. A two fold increase in I and L-FABPc mRNA occurs in starved rats. By contrast, only the I-FABPc mRNA are slightly enhanced after the hyperlipidic diet (50%). These preliminary results, which must be confirmed by further experiments, suggest a differential nutritional regulation of I and L-FABPc gene expression in rat intestine.

Animals↗
PubMed1990

Effect of albumin on oleic acid lymphatic absorption in rats.

1. The aim of this study was to investigate how fatty acid absorption was affected when exogenous fatty acids were complexed with albumin in absence of bile. Experiments were carried out in vivo, in order to study overall absorption processes. 2. An equimolar mixture of 14C oleic acid, palmitic acid and monopalmitin was infused intraduodenally in bile- and pancreatic juice-diverted rats. 3. Lipids were emulsified with either sodium taurocholate or fatty acids complexed with albumin. 4. Lymphatic lipid output was compared during the 6 hr following infusion of 90 mumol of the radioactive lipid mixture. 5. Lymphatic radioactive lipid recovery was significantly decreased by albumin. 6. Only 17% of the infused radioactivity was recovered in lymph when fatty acids were complexed with albumin against 37% when lipids were emulsified with sodium taurocholate. 7. Unrecovered lymph radioactivity was found at the distal part of intestine. Moreover, albumin significantly decreased lymph flow. 8. We conclude that undigested albumin acted at the luminal level of lipid absorption processes and specifically decreased fatty acid uptake.

Absorption↗
PubMed1990

Erucic acid metabolism in rat heart. A combined biochemical and radioautographical study.

Metabolism of Erucic Acid was studied in rat heart in comparison with that of oleic acid, particularly in relation with diet lipids. Rats were fed for 3 or 60 days a diet containing 30% of the calories of either Rapessed Oil, rich in erucic acid or sunflower seed oil rich in linoleic acid. They were I.V. injected with tritiated erucic or oleic acid. After 1 or 15 min the radioactivity recovered in heart lipids was very low whatever the diet (1 to 2%). One minute after injection of erucic acid the radioactivity was mainly recovered in the free fatty acid fraction and as untransformed erucic acid. After 15 min the major part of radioactivity was recovered in the triacylglycerol fraction which contained a high proportion of labelled oleic acid formed by shortening of erucic acid. When oleic was injected, the radioactivity was principally recovered in triacylglycerols as untransformed oleic acid whatever the experimental conditions. Electron microscopy showed that a much higher proportion of peroxisomes, was present in heart cells, following sunflower seed oil diet as compared to rapeseed oil diet. In all cases mitochondria supported the greater part of radioactivity, especially when erucic acid was injected in rats fed rapeseed oil. After sunflower seed oil, a noticeable radioactivity was observed in peroxisomes, most of them containing silver grains, especially when oleic acid was injected. According to the data reported, peroxisomes do not seem more implicated than mitochondria in the metabolism of erucic acid in myocardium.

Animals↗
PubMed1989

Effect of calcium and magnesium ions on the intestinal absorption of oleic acid in vitro.

The effect of Ca++ and Mg++ upon intestinal absorption of oleic acid was investigated using two in vitro models: rat isolated jejunal loops at 30 degrees C and 37 degrees C and mouse jejunal explants at 37 degrees C. At 30 degrees C or at 37 degrees C, Ca++ significantly increased 14C oleic acid uptake by rat isolated jejunal loops or mouse jejunal explants; at 37 degrees C, Ca++ significantly enhanced lipid exocytosis in rat intestinal loops but not in mouse jejunal explants; in both models, in the presence of Ca++ and at 37 degrees C, Mg++ significantly improved the esterification of oleic acid phospholipids and triacylglycerols, as shown by the increase in triacyglycerol synthesis in rat isolated intestinal loops or by the increase in triacylglycerols recovered from the incubation media of mouse jejunal explants; experiments carried out with rat isolated jejunal loops highlighted the determinant role of temperature in oleic acid absorption processes. The present work shows that the simultaneous presence of Ca++ and Mg++ did not impede oleic acid absorption processes but, on the contrary, enhanced them.

Animals↗