Biomedical subjects

D Pepin

Publications and source records attributed to D Pepin.

At least 19 recordsLinked to original sources

PubMed2002

Drinking water and cardiovascular disease.

A link between cardiovascular disease (CVD) mortality and the hardness of drinking water (DW) is suggested by about 30 epidemiological studies performed worldwide in the general population since 1957. This review examines the main ecological studies, case-control studies and cohort studies, published between 1960 and 2000. Attention is paid to the problem of interpretation of this typical result of environmental epidemiology. Some studies focused on the role played by inorganic elements known as DW contaminants (mainly, As, Pb) and above all on the role of the magnesium content of DW and its cardioprotective effects. To date, it would be impossible to understand this environmental findings without large intervention studies performed in well-controlled public health programs.

Cardiovascular Diseases↗

PubMed2001

Basal production of pentane in expired gas from healthy humans.

BACKGROUND: Pentane in exhaled gas is often used as an index of lipoperoxidation, but today, there is no standardization for its measurement. In this study, with our technical experience, we determined basal production of pentane in healthy subjects, and we evaluated variability of pentane flow 1 month later. METHODS: 18 subjects inhaled hydrocarbon-free air (HCFA) in order to realize a lung washout. Ambient air and three samples (at T0, T10, T30 min) of expired gas were concentrated using a "trap-and-purge" procedure. For the analysis of pentane, an Al(2)O(3)/KCl plot column contained in a gas chromatograph equipped with a flame ionization detector was used. RESULTS: After 10 min of washout, mean (+/-SD) exhalation rate of pentane was 1+/-0.6 pmol min(-1) kg(-1). After 30 min of washout, mean (+/-SD) exhalation rate of pentane was 0.7+/-0.5 pmol min(-1) kg(-1). No significant difference in pentane flow was shown 1 month later for eight subjects who repeated the protocol. CONCLUSION: With our results and data of the literature, exhalation rates of pentane from healthy adults appear to range between 0.3 and 2 pmol min(-1) kg(-1). The variability of pentane flow 1 month later seems not very important.

Adult↗

PubMed2001

Oxygen toxicity: simultaneous measure of pentane and malondialdehyde in humans exposed to hyperoxia.

In order to estimate cell damage caused by free radicals during oxygenotherapy, we investigated the time course of two markers of lipoperoxidation: pentane in breath and malondialdehyde (MDA) in blood during brief normobaric hyperoxia. Nine healthy subjects inhaled hydrocarbon-free air (HCFA) for 30 minutes, hydrocarbon-free 100% O2 (HCFO2) for 125 minutes and then HCFA for 70 minutes. After 15 minutes of washout with HCFA, ambient pentane was eliminated. After HCFO2, at T175 versus T30 (i.e., 145 min from the start of 100% HCFO2), pentane production increased (P< 0.05). MDA rose significantly at T155 min (i.e., 125 min from the start of HCFO2), versus T30 (P< 0.01). These results suggest that acute hyperoxia causes a moderate increase in lipid peroxidation in healthy subjects. The increase of pentane and MDA confirms that acute hyperoxia induces lipid peroxidation in healthy subjects.

Aged↗

PubMed2000

Geographic variation of the mortality from cardiovascular disease and drinking water in a French small area (Puy de Dome).

Cardiovascular disease (CVD) has been the first cause of mortality in the population of Puy de Dôme (PDD) (France) between 1988 and 1992. The mortality rates are significantly higher than those observed in the whole population of France (for the female population, 354.8 versus 327.3 per 100,000 persons/year and for the male population, 335.7 versus 287.9 per 100,000 persons/year). Moreover, an ecological study, which used the Standardized Mortality Ratios (SMR) and performed at the canton level, has allowed a special variation of mortality from CVD in PDD to be described. A decreased gradient of mortality (especially, "Ischemic Heart diseases" [ICM-9, codes 410-414] and "Cerebro-vascular Diseases" [ICM-9, codes 430-438]) has been observed from the periphery (rural area) to the middle (urban area) of PDD. Moreover, a statistically significant negative relationship has been observed between the hardness of the drinking water supplies in PDD and the CVD mortality data (i.e., the lower the hardness of drinking water, the higher the SMR). Although, the low hardness of drinking water can contribute to the high CVD mortality observed among the PDD population, the role of other risk factors (i.e., biological, nutritional) must also be taken into consideration in further prospective studies.

Adolescent↗

PubMed1999

Effects of humic substances and phenolic compounds on the in vitro toxicity of aluminium.

The effects of natural chelators [humic acids (HA), caffeic acid (CFA), p-coumaric acid (PCA), protocatechuic acid (PA), vanillic acid (VA), salicylic acid (SA), and 4-hydroxyacetophenone (HY)] and effects of well-known chelators [EDTA and citric acid (CA)] on the in vitro toxicity of aluminium (Al) were investigated with the L-929 murine, Vero simian, and MRC-5 human cell lines. Moderate in vitro cytotoxic effects were induced by Al on the three cell lines (IC(50) values ranking from 5.6 to 7.6 mM). Furthermore, an increased toxicity was observed when Al was concurrently administered with CA, SA, VA, PCA, and HY. Inversely, significant cytoprotective effects were noted with EDTA, HA, CFA, and PA. The role of chelators, and especially the position and the number of reactive moieties of the phenolic compounds tested, can be highlighted to explain the different toxicological Al behavior observed.

Aluminum↗

PubMed1999

Tetrahymena pyriformis: a tool for toxicological studies. A review.

Among protozoa, Tetrahymena pyriformis is the most commonly ciliated model used for laboratory research. After a brief description of the morphology and biology of Tetrahymena pyriformis, this article focuses on the most important and recent investigations performed with this species in toxicology and ecotoxicology. The methodological features of its culture, and main tests, based on cell growth rate, biochemical markers, behavioral changes and motility, are discussed. Examples of xenobiotics (organic and inorganic substances, pharmaceutical drugs, water pollutants) tested with Tetrahymena pyriformis are also given.

Animals↗

PubMed1998

Detection of BCR-ABL transcripts in acute lymphoblastic leukemia in Indian patients.

Thirty-three patients with acute lymphoblastic leukemia (ALL) from India were studied for the presence of BCR-ABL chimeric transcripts, by a seminested cDNA-PCR. We report the presence of BCR-ABL chimeric transcripts in 4/17 (24%) children (under 15 years) and 3/16 (19%) adults (15-50 years). This is in sharp contrast to the published literature from the West where the presence of BCR-ABL has been reported in only 2-5% children and 35% adults. Whether the presence of BCR-ABL fusion mRNA, which is generally an attribute of ALL in adults and of poorer prognosis, may contribute to chemo-incurability in young Indian patients, remains to be seen, as a larger number of patients are studied for treatment outcome and survival on uniform therapy protocols.

Adolescent↗

PubMed1997

Toxicity assessment of 16 inorganic environmental pollutants by six bioassays.

The relative toxicity of 16 environmental pollutants, such as inorganic elements (Ba, Cd, Co, Cr, Cu, Fe, Ge, Hg, Mn, Nb, Pb, Sb, Sn, Ti, V, and Zn), is evaluated on the L-929 established cell line of murine fibroblasts, with five bioassays [RNA synthesis rate assay (RNA), MTT reduction assay (MTT), neutral red incorporation assay (NRI), Coomassie blue assay, and cellular growth rate assay], and on the ciliated protozoa Tetrahymena pyriformis GL [doubling time of T. pyriformis GL population assay (DTP)]. For each inorganic substance, the six bioassays allowed the toxicological index IC50 ("inhibitory concentration 50%") to be calculated. The IC50 values are useful to rank the tested elements and to compare the features of the six bioassays. The most sensitive assays were the RNA, MTT, NRI, and DTP assays. Moreover, the in vitro IC50 values correlated with the in vivo LD50 values; these results were close to those obtained with established lines of human, murine, or fish cells. The sensitivity and the complementarity of these bioassays would be in favor of their incorporation in a "battery" of tests used for toxicological screening studies of xenobiotics.

Animals↗

PubMed1997

Study of magnesium bioavailability using stable isotopes and the inductively-coupled plasma mass spectrometry technique in the rat: single and double labelling approaches.

The present work aimed to investigate the feasibility of using stable isotopes and inductively-coupled plasma mass spectrometry (ICP/MS) to study Mg absorption in rats. Male Wistar rats, aged 7 weeks and weighing 180 g, were used. They were fed on a semi-purified diet containing 1070 mg Mg/kg, and had free access to feed and distilled water. In the first experiment, after a 16 d adaptation period, two doses of enriched 25Mg (6 and 12 mg) were administered by oral intubation, faeces and urine were collected daily and blood was sampled. Isotope ratios were determined by ICP/MS. 'True' absorption values, using the faecal isotope data, were 0.63 and 0.56 in rats receiving 6 and 12 mg 25Mg respectively, while apparent absorption was 0.50 for two successive periods of metabolic balance studies. Moreover, the oral isotope administration resulted in a measurable isotopic enrichment in plasma within hours which was still detectable on the third day following the isotope administration. In the second experiment, investigating the double labelling technique, similar rats were dosed simultaneously with 5 mg 26Mg orally (premixed with diet) and 0.29 mg 25Mg intravenously. The calculated Mg true absorption values were very similar when calculated from blood or urine data (0.38) but were lower than that obtained from faecal data (0.50). The possible causes of such an unexpected difference and limits of the double labelling technique for Mg absorption are discussed here. Together these results indicate that although 25Mg and 26Mg isotopes have high natural abundance, the described methodology permits meaningful investigations of Mg bioavailability and metabolism.

Administration, Oral↗

PubMed1995

Microplate technique for screening and assessing cytotoxicity of xenobiotics with Tetrahymena pyriformis.

The microplate technique (MT) is developed and compared to the usual flask technique (FT) of Tetrahymena pyriformis GL cultures for assessing toxic effects of organic and inorganic substances on this ciliated protozoa model. Applied to the IC50 determination of 29 xenobiotics, the MT demonstrated good correlation with the FT (Y = 0.991X + 0.012, r = 0.94, P < 0.0001). The MT is rapid, easy-to-handle, inexpensive, and statistically reliable and, so, may be helpful for screening investigations of water-soluble xenobiotics.

Animals↗

PubMed1994

Comparative study of two in vitro models (L-929 fibroblasts and Tetrahymena pyriformis GL) for the cytotoxicological evaluation of packaged water.

The preservation of 234 samples of water packaged in polychloride vinyl (PVC), polyethylene terephthalate (PET) and glass-bottles was concurrently evaluated using both classical chemical analysis oriented to finding organic and inorganic substances which could have been leached by the packaging and in vitro toxicological bioassays using two models: the L-929 established cell line of fibroblasts and the ciliated protozoa Tetrahymena pyriformis GL. Although no significant abnormality was detected with the chemical analysis, cytotoxicity was detected with both models in some samples of water bottled for > 18 months, for either PVC, PET or glass-packaging. However, statistical analysis did not allow a mathematical relationship between the cytotoxic effects, the length of storage and the packaging to be demonstrated.

Animals↗

PubMed1994

Analysis of BCR/ABL transcripts in chronic myeloid patients by nested PCR using an immunoassay-like detection format.

We describe an 'immunoassay-like' detection format, based on the AMPLICIS technique for the routine detection of BCR/ABL transcripts in leukaemic patients. The AMPLICIS technique is characterized as a nested PCR coupled to solid phase isotopic or non-isotopic detection of PCR products. Comparison between this assay and a conventional PCR technique using Southern-blot analysis provided a good correlation between the two procedures. The assay, easier and faster than the conventional one, gives access to automation and therefore appears well suited for the routine screening of BCR/ABL chimaeric mRNAs.

Base Sequence↗

PubMed1991

Effect of simvastatin on the synthesis and secretion of lipoproteins in relation to the metabolism of cholesterol in cultured hepatocytes.

In primary culture of rat hepatocytes, simvastatin, a powerful HMGCoA reductase inhibitor, inhibited acetate incorporation into cellular and secreted cholesterol and cholesteryl-esters, without any significant effect on triacylglycerol synthesis and secretion. When applied to the culture for 24 h at 10(-7) M, a concentration shown to inhibit cholesterol synthesis by 61%, simvastatin increased apolipoprotein BH and BL synthesis and secretion and strongly decreased apolipoprotein AI synthesis and secretion whereas apolipoprotein AIV remained unaffected. The synthesis and secretion of apolipoprotein E was only slightly affected in contrast with other situations where cholesterol synthesis decreased. All of these modifications occurred at a post-transcriptional level, as the corresponding messenger RNAs of the apolipoproteins did not vary. These results suggest that either the drug itself or variations in cholesterol synthesis might be involved in apo B and apo AI synthesis and secretion.

Animals↗

PubMed1990

Partial apolipoprotein E-beta-galactosidase fusion protein expressed in Escherichia coli retains binding activity to the LDL(B/E) receptor.

A partial rat apo E-beta-galactosidase fusion protein was produced in Escherichia coli Y1089 infected with recombinant lambda GT11 obtained by immunoscreening of a rat liver cDNA library with an anti-rat LDL antiserum. Partial cDNA overlapped the apo E mRNA sequence coding for apo E binding domain towards the LDL(B/E) receptor up to codon for Arg-139. Fusion protein specifically bound to human fibroblasts. The high-affinity component exhibited a Kd of 5 x 10(-8) M and 4.1 x 10(5) sites per cell. Fusion protein binding to fibroblasts was mediated by their apo E moiety and not by beta-galactosidase since: (1) specific binding of fusion protein was competed out by human LDL; (2) beta-galactosidase did not compete with fusion protein binding; and (3) human fibroblasts from a patient with familial hypercholesterolemia, deficient in LDL(B/E) receptor, bound fusion protein 10-times lower than control fibroblasts. It was demonstrated that partial fusion protein retained the functional activity of the native apo E. However, compared to full-length native or engineered apo E, fusion protein was able to bind fibroblasts without being complexed with phospholipids. Fusion proteins might be a useful tool for studying the functional efficiency of the LDL(B/E) receptor and for mapping residues and domains involved in the binding process.

Apolipoproteins E↗

PubMed1990

Eicosanoid synthesis in children with cholestatic disease.

The possibility of malabsorption of triglycerides contained in the diets of children with cholestasis suggests a deficiency of essential fatty acids and, therefore, probable effects on eicosanoid metabolism. Children with either biliary atresia (BA) or syndromatic paucity of interlobular bile ducts (PILBD) were evaluated as to plasma and platelet total lipid fatty acid composition and synthesis of prostaglandins (PG) E1, PGE2, PGI2, PGF2, and thromboxane (TXB2) by whole blood incubated at 37 degrees C for 10 min. In both diseases linoleate deficiency was present as shown by low 18:2 fatty acids in plasma lipids. The children with BA had lower plasma arachidonate than controls but normal eicosanoid synthesis except for excess PGI2. Those with PILBD had low platelet arachidonate and were severely deficient in TXB2 synthesis (less than 10% of controls). Three children with PILBD were fed a supplement of structured triglyceride (Captex 810) intended to provide as much as 10% of energy as linoleate for 2-3 months. Results for these three cases suggested that insufficient linoleate was absorbed to increase plasma linoleate and differences in eicosanoids could not be attributed to linoleate supplementation.

Arachidonic Acid↗

PubMed1989

Fate of fatty acids taken up as cholesteryl ester by rat hepatocytes in primary culture from high-density lipoprotein.

Primary cultures of rat hepatocytes were incubated in the presence of high-density lipoproteins (HDL) labelled with [1-14C]oleyl or [1-14C]linoleyl cholesteryl ester. Labelled HDL were prepared by selective delipidation with heptane, relipidation and sequential ultracentrifugations. Hepatocytes took up cholesteryl esters and cholesteryl ether their non-hydrolizable analog, at the same rate. The uptake increased with time, the cholesteryl ester/protein ratio and the amount of added HDL. It was not dependent on the nature of acyl chain or on the nature of the bond. The uptake did not depend on a specific interaction between HDL and cell membranes, since cholesteryl ester was taken up from HDL to the same extent as from albumin complexes. Linoleic and oleic acids released from cholesteryl esters taken up by hepatocytes were mainly reesterified into phosphatidylcholine and triacylglycerols. Linoleic acid was preferentially channelled into PC. A portion of these lipids were secreted by hepatocytes during a 24-h reincubation in a medium devoid of lipoprotein. Nearly the same amount of radioactivity was recovered in secreted phospholipids as in secreted triacylglycerols, in contrast with hepatocytes labelled with free fatty acids which secreted very little radioactivity as phospholipids. From these results and the high content in polyunsaturated fatty acids of cholesteryl esters, one can hypothesize that hepatic cholesteryl ester uptake may contribute to biliary phosphatidylcholine production, and therefore to polyunsaturated fatty acid sparing.

Animals↗

PubMed1989

Arachidonate cannot be released directly from diacyl-sn-glycero-3-phosphocholine in thrombin-stimulated platelets.

The origin of the arachidonate released from platelets on stimulation with thrombin was investigated by comparing the specific activities of released arachidonate and of arachidonoyl-containing phospholipids using rat platelets prelabelled with arachidonate. Quantification of the released arachidonate was determined in the presence of BW 755 C, a dual cyclo-oxygenase/lipoxygenase inhibitor, which was found not to modify the arachidonate mobilization between the platelet phospholipids. The phospholipid molecular species were analysed by h.p.l.c. of diradylglycerol benzoate derivatives of diacyl, alkylacyl and alkenylacyl classes. The labelled/unlabelled arachidonate ratio varied greatly in the phospholipids depending on whether an ether or acyl bond was present in sn-1 position of the glycerol, on the length and degree of unsaturation of this fatty chain and on the polar head group. Between 15 s and 5 min of stimulation by thrombin, the released arachidonate kept a constant specific activity which was considerably lower than the specific activity of diacyl-GPC. The specific activity of the released arachidonate was intermediate between the specific activities of the 16:0-20:4 and 18:0-20:4 species of diacyl-GPI and diacyl-GPE, and corresponded to the mean specific activity of alkylacyl-GPC. The data indicate that the released arachidonate cannot come directly from diacyl-GPC, and that two phospholipids in particular can act as direct precursors of the released arachidonate. These are (1) the alkylacyl-GPC and (2) the diacyl-GPE whose hydrolysis would induce an arachidonate transfer from diacyl-GPC.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1988

Selective channelling of arachidonic and linoleic acids into glycerolipids of rat hepatocytes in primary culture.

Rat hepatocytes in primary culture were incubated with a mixture of linoleic and arachidonic acid at various total fatty acid/serum albumin molar ratios. Mixed fatty acids were taken up at the same rate and distributed with the same pattern as fatty acids added separately. The rates of total uptake, incorporation into hepatocyte and secreted triacylglycerols and beta-oxidation were linearly related to the fatty acid/albumin ratios, whereas the rate of incorporation into phospholipids was saturable. Neither the uptake rate nor the distribution of both fatty acids considered together varied with the arachidonic acid/linoleic acid molar ratio. Changes in this ratio and in the uptake rate led to significant variations in the respective fate of the fatty acids. The preferential channelling of arachidonic acid versus linoleic acid into beta-oxidation and phosphatidylinositol was greatest at a low uptake rate and then decreased as the uptake rose. Conversely, the preferential channelling of arachidonic acid versus linoleic acid into phosphatidylcholine, but not phosphatidylethanolamine, increased with the uptake rate. Moreover, both arachidonic acid and linoleic acid were preferentially incorporated into the 1-palmitoyl molecular species of phosphatidylcholine and phosphatidylethanolamine at a low uptake rate, and of phosphatidylcholine at a high uptake rate. This could be related to the synthesis of biliary phosphatidylcholine, of which 1-palmitoyl-2-linoleoyl and 1-palmitoyl-2-arachidonoyl are the main molecular species. Linoleic and arachidonic acid were selectively distributed into distinct metabolic pools of triacylglycerol, the intrahepatocyte pool which preferentially incorporated linoleic acid at a low uptake rate and the secreted pool in which the relative enrichment of arachidonic acid increased with the uptake rate. This strengthens the central role of hepatic secretion in the supply of arachidonic acid to peripheral tissues.

Animals↗