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Biomedical subjects

H J Parra

Publications and source records attributed to H J Parra.

At least 19 recordsLinked to original sources

[Situation of the envenomations by snakebites in Congo-Brazzaville: epidemiological, clinical and therapeutic approaches].

A retrospective study was carried out in six areas of Congo and in the town of Brazzaville for the period between 2000 and 2004 in order to evaluate the incidence, lethality, treatments and the used drugs in cases of snakebites. We associated a retrospective survey using health centre registers (11 centres) and a retrospective survey based on the staff statements of village communities (42) and private pharmacies and drug centrals. The questionnaire related to the snakebites (identification of victims, place of bite, symptoms and treatment) was used in communities. The total case fatality rate was relatively low (3,11%). The incidence of the estimated snakebites was higher in villages (221) than in health centres (165). But, lethality was equal in the two study clusters (6 cases versus 6 cases). There was no difference of cases rate between male and female subjects. Around urban areas, many victims consulted health centre and in rural area, many victims resorted systematically to traditional practitioners. In drug centrals and private pharmacies of Brazzaville, drugs against envenomations were proposed, respectively, by one and two structures. In health centres these drugs were not available. This evaluation could be underestimated as many victims consulted traditional practitioners. This explains why collecting data from health centre registers is not sufficient to evaluate the importance of envenomations in our study area.

Congo↗

Genetic subtypes of HIV type 1 in Republic of Congo.

To assess the molecular epidemiology of HIV-1 in Republic of Congo (Congo), we investigated 29 HIV-1s obtained from 82 Congolese AIDS and ARC patients in 1996 and 1997. Part of the env region including the V3 loop was phylogenetically analyzed. The genotypes observed were varied: of 29 specimens, 12 (41 %) were subtype A, 1 (3%) was subtype D, 6 (21%) were subtype G, 6 (21%) were subtype H, 2 (7%) were subtype J, and 2 (7%) could not be classified as any known subtypes (U, unclassified). The heterogeneous profile of HIV-1 infection was different from the profiles of neighboring Central African countries. These data show that subtypes G and H as well as subtype A were circulating with high prevalence. The fact that new genetic subtypes (J and U) are circulating indicates a need for a greater surveillance for these subtypes both in Congo as well as in other parts of the world.

AIDS-Related Complex↗

Plasma cholesterol and endogenous cholesterol synthesis during refeeding in anorexia nervosa.

Normal or high levels of cholesterol have been measured in patients with anorexia nervosa (AN). Given that cholesterol intake in AN is usually very low, the reasons for this anomaly are not clearly understood. We studied lipid and lipoprotein profiles and endogenous cholesterol synthesis, estimated by serum lathosterol, in a population of 14 girls with AN, before and during a period of 30 days refeeding. The initial body mass index (BMI) of the patients was 13.41+/-1.62 kg/m(2). No changes were observed during refeeding in endocrine parameters (ACTH, cortisol and estradiol). At Day 0 the lipids data measured here showed normal levels of triglycerides, and total cholesterol at the upper limits of the normal range (5.44+/-1 mmol/l). At this time, total and LDL cholesterol were negatively correlated with transthyretin and BMI. Serum lathosterol (a precursor in cholesterol synthesis pathway) increased significantly (5.99+/-1.75 (Day 0) vs. 8.39+/-2.96 (Day 30); P=0.02) while there was a significant decrease in apo B (0.79+/-0.33 (Day 0) vs. 0. 60+/-0.17 g/l (Day 30), P=0.02) with refeeding. Thus, patients with initial high cholesterol levels have the worst nutritional status and high cholesterol levels are not related to a de novo synthesis. This profile returns to normal with refeeding. An increase of cellular cholesterol uptake may be responsible for this apparently paradoxical evolution with increase of cholesterol synthesis and decrease of apo B during renutrition.

Adolescent↗

Genetic diversity of HIV-1 group M from Cameroon and Republic of Congo.

We analyzed 57 HIV-1 isolates from Cameroon and the Republic of Congo, with respect to the env C2V3 and/or the pol integrase regions. The results indicated that the topology of the pol tree correlated well with that of the env tree for four clusters of subtype D, F G and H, suggesting that these trees reflect the true evolution of the overall genome structures of these subtypes. However, of 22 Cameroonian isolates that were classified as subtype A based on env, 20 of them diverged in their pol sequence into two lineages that were completely different from the prototypical subtype A, tentatively designated as subtypes A1 and A2. The subtype A1 isolates (6 out of 22) were related in their env C2V3 regions with prototypical subtype A strain, but in their pol regions, they formed an independent cluster that diverged from known HIV-1 subtypes so far reported (except for subtypes I and J). The subtype A2 isolates (14 out of 22), which represent the major epidemic type of HIV-1 in Cameroon, clustered distinctly in both the env and pol trees with the recently described A/G mosaic strains from Nigeria and Djibouti. These two lineages were not spreading in the neighboring Republic of Congo.

Amino Acid Sequence↗

Beneficial effect on serum apo AI, apo B and Lp AI levels of Ramadan fasting.

In order to investigate for the first time in Morocco the effect of fasting in Ramadan, the ninth lunar month of the muslim year, on lipoprotein metabolism, we determined the levels of serum apolipoproteins; apolipoprotein AI (apo AI), apo B, apo AIV and those of lipoprotein particles; apo AI-containing lipoprotein particles (Lp AI) and also apo AI and apo AII containing lipoprotein particles (Lp AI:AII) in a group of 32 healthy, volunteer adult males. Determination of all these parameters was carried out on each week of the month of Ramadan and the results are compared with the pre-fasting and the post-fasting values. Ramadan fasting reduces significantly serum apo B (P < 0.05), while serum apo AI is significantly increased (P < 0.05) compared with the pre-fasting period. The increase of apo AI occurred on day 29 of Ramadan by 11.8%. Serum apo AIV was unchanged during the fasting period indicating that food intake during Ramadan is not based on lipid diet. The observed diet pattern during Ramadan showed an increase of total energy intake based on carbohydrates (+1.4% of total energy), proteins (+0.4% of total energy) but not on fat (-0.7% of total energy), compared with a usual diet used in the rest of the year. The fat diet is high in monounsaturated (P < 0.05) and polyunsaturated fatty acid in contrast to saturated fatty acid which decreased (P < 0.05) during Ramadan. On the other hand, analysis of serum Lp AI and Lp AI:AII showed that the levels of Lp AI:AII were unchanged but those of Lp AI were significantly increased (P < 0.01) at the end of Ramadan. These findings show that feeding behaviour that occurs during Ramadan beneficially affects serum apolipoprotein metabolism and may contribute to prevention of cardiovascular diseases.

Adult↗

Polymorphisms of the tumour necrosis factor-alpha gene, coronary heart disease and obesity.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is a cytokine that has multiple functions. Through its effects on lipid metabolism, coagulation, insulin resistance and endothelial function, TNF-alpha could be involved in cardiovascular pathophysiology. Given this possibility, we hypothesized that polymorphisms of the TNF-alpha gene might be associated with a predisposition to coronary heart disease (CHD). METHODS: The entire coding region and 1053 bp upstream of the transcription start site of the TNF-alpha gene were screened for polymorphisms using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing. Five polymorphisms were identified: four were located in the upstream region at positions -857, -851, -308, -238 from the first transcribed nucleotide and one was found in a non-translated region at position +691. Six-hundred and forty-one patients with myocardial infarction (MI) and 710 control subjects from the ECTIM Study were genotyped. RESULTS: The genotype frequencies were similar in cases and control subjects in the high-risk population of Belfast and in France; however, the TNF-alpha/-308A allele was more frequent in Belfast than in France (0.242 vs. 0.157; P < 0.0001), and carriers of this allele were more frequently obese than non-carriers [1.52 (1.15-1.99), P < 0.004]. No associations were found for the other polymorphisms. CONCLUSIONS: These results suggest that polymorphisms of the TNF-alpha gene are unlikely to contribute to CHD risk in an important way, but the TNF-alpha/-308 polymorphism should be investigated further in relation to obesity.

Adult↗

Postprandial lipaemia is associated with increased levels of apolipoprotein A-IV in the triacylglycerol-rich fraction and decreased levels in the denser plasma fractions.

Apolipoprotein (apo) A-IV is primarily associated with HDL or with the lipoprotein-free fraction of plasma, and in small amounts with chylomicrons and VLDL. The aim of the present study was to assess the effect of a fatty meal on the postprandial variation in plasma apo A-IV and on its distribution among lipoprotein fractions following absorption of fat. Twenty healthy male subjects participated in the study. After an overnight fast, subjects were given a fatty breakfast containing 1 g fat/kg body weight (% energy: fat 65, carbohydrate 20; protein 15). Blood samples were taken every hour during the next 10 h. Apo A-IV was measured by ELISA. Postprandial lipaemia was associated with a moderate, although significant, increase in the plasma levels of apo A-IV. Apo A-IV increased from the median baseline value of 0.15 g/l to 0.165 g/l (median +17%; P < 0.01) 5 h after fat ingestion. The postprandial peak of apo A-IV occurred 1 h after the triacylglycerol peak. There were no statistically significant correlations between baseline lipids, baseline apo A-IV and postprandial changes in apo A-IV levels, or between postprandial changes in lipids and apo A-IV at any time. To assess apo A-IV distribution among lipoproteins, plasma was fractionated by fast performance liquid chromatography at baseline and 3, 6 and 10 h postprandially. There was a substantial heterogeneity in the apo A-IV distribution among lipoproteins following the fatty meal. At 3 h after fat ingestion, apo A-IV levels increased in the triacyglycerol-rich lipoprotein (TRL) fraction and decreased in the denser plasma fraction. At 6 h after the fatty meal, apo A-IV was still present in the TRL but was decreased in the HDL fractions. The findings of the present study support the concept that apo A-IV particles transfer from the denser plasma fraction to TRL during postprandial lipaemia.

Adult↗

Apolipoprotein AIV of human interstitial fluid is associated with apolipoprotein AI-containing but not with AII-containing particles.

Apolipoproteins and lipoprotein particles from human interstitial fluid and plasma were analyzed. The interstitial fluid was enriched in apolipoproteins AI, AII, and AIV compared with apo B, apo CIII, and apo E, LpAI was found to contain apo AIV which was absent from LpAI: AII. Moreover, the bulk of lecithin-cholesterol acyl-transferase was present in LpAI. The concentration range of these particles was in agreement with those required in vitro for cholesterol efflux. Thus the interstitial fluid contains particles in which two agonists but no antagonists of cholesterol efflux are associated with lecithin-cholesterol acyltransferase activity. This supports apolipoprotein AI- and/or AIV-containing particles playing a critical role in the first step of reverse cholesterol transport.

Adult↗

Alteration of the lipid and apolipoprotein contents of lipoprotein (a) in haemodialysis patients.

BACKGROUND: To examine the possible alteration in Lp(a) composition, protein and lipid contents of Lp(a) were determined in 10 haemodialysis patients (HD) matched with 10 controls (C) for apo(a) phenotypes. METHODS: All subjects (HD and C) had Lp(a) concentrations greater than 30 mg/dl (mean+/-SD : 82.3+/-41.4 vs 49. 3+22.5 mg/dl), a concentration which has been determined to be associated with an elevated cardiovascular risk. Apo(a)-containing particles were isolated by immunoaffinity chromatography using a monoclonal anti-apo(a) antibody. RESULTS: The molar concentrations of lipid and protein constituents of immunoaffinity isolated Lp(a) were expressed as number of moles per mole of apo(a). Lp(a) from HD patients were significantly richer in apo Cl11 (P<0.05) and triglycerides (TG) (P<0.05), compared to those of controls. Molar ratios of apo B, apo E, cholesterol and phospholipid s per apo(a)-containing particles were in the same range in both groups. CONCLUSION: Lp(a) from HD patients is characterized by an elevated content in TH and apo Cl11 in comparison with those of controls. Further studies are needed to evaluate in HD patients the contribution of changes in Lp(a) composition towards the metabolism of these particles.

Adult↗

Apolipoprotein AI and apolipoprotein B containing particle analysis in normolipidemic hemodialyzed patients: evidence of free apolipoprotein E.

Whole plasma from 6 normolipidemic chronic renal failure (CRF) patients undergoing hemodialysis treatment was passed through the anti-apolipoprotein (Apo) AI immunosorbent column connected to the anti-Apo B immunoaffinity column. Apo AI and B containing particles were analyzed for lipid and Apo contents. The results were compared with findings obtained in age-matched normolipidemic healthy controls. Although plasma Apo AI and AII levels decreased in CRF patients, the concentrations of Apo CII, CIII, and E coeluted with Apo AI were similar to those of the controls. The slightly elevated plasma concentrations of Apo CII and CIII in the CRF patients studied were shown to be associated with Apo B containing particles. The nonretained fraction from both groups contains no Apo AI and no Apo B, but still contains lipids and other Apo such as Apo AII and Apo CII. The occurrence of approximately 29% of plasma Apo E in this fraction constitutes the main abnormality found in these patients (< 5% in controls). A two-phase electroimmunoassay shows that this Apo E did not correspond to the plasma E-AII complex. These findings show that the compositional alterations of Apo AI and Apo B containing particles in CRF patients were observed even in normolipidemic patients and suggest that the kidney may play a metabolic role in the removal of free forms of lipoprotein particles such as free Apo E.

Apolipoprotein A-I↗

Native like structure and stability of apo AI in a n-propanol/water solution as determined by 13C NMR.

To elucidate the molecular details of the conformation of apolipoprotein AI (apo AI), we have developed an approach related to the solubilization of this protein in 30% n-propanol. We have previously reported the promotion of a native-like structure for apo AI solubilized in n-propanol, as depicted by circular dichroism, fluorescence, and limited proteolytic digestion as compared to the lipid associated form of apo AI. In the present study, we labeled the Lys residues of apo AI with 13C by reductive methylation and used 13C NMR to confirm the formation of a native-like structure of apo AI in this environment. Furthermore, by the above criteria (circular dichroism and 13C NMR) and by using urea and temperature as denaturing agents, we show that the denaturation of the native-like structure of apo AI in n-propanol is a biphasic process. These studies show that in 30% n-propanol, apo AI contains two independently folded structural domains, of markedly different stabilities that might correspond to the amino-terminal and the carboxy-terminal halves of the molecule.

1-Propanol↗

Sources of variability of human plasma apolipoprotein A-IV levels and relationships with lipid metabolism.

Plasma apolipoprotein (apo) A-IV concentration was determined by immunoelectrophoretic assay (EIA) in 119 nuclear families. No significant effect of concomitants such as age, weight, height, body mass index, tobacco, and alcohol consumption was observed on apo A-IV levels in men and in boys. In women, contraceptive use and hormonal status affected apo A-IV levels. In girls, only age influenced the quantitative phenotype. After adjusting by specific concomitants significant correlations were observed between apo A-IV levels and triglycerides, apolipoprotein A-I and apo B levels, suggesting a role of apolipoprotein A-IV in the hepatic lipid metabolism. Intrafamilial correlations were estimated to investigate the plausibility of a common family factor. The results obtained in this study showed a significant correlation between family members with the exception of mother-daughter pairs. Using a variance components model, the contribution of genetic and environmental factors was then investigated. Different statistical models were used and two major hypotheses were statistically acceptable: the first hypothesis supports that shared and specific environmental factors explain 35 and 65%, respectively, of the total adjusted plasma apo A-IV variation. The fraction of apo A-IV variability attributable to genetic factors was null. The second hypothesis supports that the fraction of variability attributable to apo A-IV genetic variation is 67% and the common spouse environmental factors are responsible for 33% of the total variability and no specific environmental effect was found. Among the two hypotheses, taking account of the metabolism function, we support the first one without excluding gene-environment interactions which could mask the genetic influence.

Adult↗

DNA polymorphisms of human apolipoprotein A-IV gene: frequency and effects on lipid, lipoprotein and apolipoprotein levels in a French population.

Genetic polymorphisms of apolipoprotein (apo) A-IV have been shown to influence lipoprotein metabolism in some human populations. In this study, we have evaluated the physiological effect of three apo A-IV polymorphisms (Gln360- > His, Thr347- > Ser and XbaI within the second intron of the apo A-IV gene), in a French population, on seven quantitative traits: total cholesterol and triglycerides, cholesterol of HDL, apo A-IV, apo B, apo A-I and glucose. The polymorphism at amino-acid 360 was determined by direct analysis of polymerase chain reaction products. The allele frequencies were 0.92 for the A-IV1 and 0.08 for the A-IV2 allele. The genetic polymorphism at codon 347 was investigated by allele-specific oligonucleotide hybridization. The allele frequencies of the two alleles, A-IV347Thr and A-IV347Ser, were 0.78 and 0.22, respectively. The XbaI polymorphism was investigated by polymerase chain reaction followed by XbaI restriction enzyme digestion of the amplified products. The frequencies of the two apo A-IV alleles, XbaI-1 and XbaI-2, were 0.79 and 0.21, respectively. None of the three apo A-IV polymorphisms had a significant effect on lipoprotein, apolipoprotein and glucose levels.

Adult↗

Two-site enzyme immunoassay of cholesteryl ester transfer protein with monoclonal and oligoclonal antibodies.

We developed a sandwich-type enzyme immunoassay to measure cholesteryl ester transfer protein (CETP) mass in human plasma. A specific monoclonal antibody (TP-4) that recognizes an epitope located in the C-terminal domain was used for antigen capture and an anti-CETP peptide antibody directed against the 290-306 residue was used for detection. Bound antibodies were revealed with an antibody-peroxidase conjugate specific for rabbit IgG. The presence of 10 mL/L Triton X-100 in the incubation buffer increased antigen exposure of CETP in plasma. The curves for CETP in standard plasma and partially purified CETP were parallel. This technique is rapid (results within 6 h), accurate, precise (mean intra- and interassay CVs 3.6% and 8.4%, respectively), and simple to perform. Assay sensitivity is at microgram concentrations, with a working range of 20-200 micrograms/L. In 40 normolipidemic healthy subjects, the mean CETP concentration in plasma was 1.1 +/- 0.4 mg/L. A strong correlation between CETP concentration and CETP activity (r = 0.91, n = 42) was observed. In plasma, the bulk of CETP was found in high-density lipoprotein fractions. Therefore, this assay may be a useful tool for investigations of CETP and its significance in relevant diseases.

Antibodies↗

Apolipoprotein B signal peptide polymorphism in patients with myocardial infarction and controls. "The ECTIM study".

We report the allele frequencies of the apolipoprotein B (Apo B) signal peptide polymorphism in patients with myocardial infarction and compare them with controls. The first sample consists of 197 myocardial infarction patients and 168 controls from Belfast (UK). The second sample consists of 167 myocardial infarction patients and 205 controls from Strasbourg (France), and the third consists of 71 patients and 146 controls from Haute-Garonne (Toulouse, France). No significant differences were observed in the frequency distribution of genotypes among cases and controls or between populations. However, there were more rare homozygotes in the Belfast cases. Significant associations were observed between the Apo B signal peptide polymorphism and mean levels of total cholesterol, low density lipoprotein cholesterol, Apo B and lipoprotein particles containing Apo (a) [Lp(a)] in the Strasbourg control population. Individuals homozygous for the rare allele had higher levels of these lipid parameters. In Belfast, although not statistically significant, the Apo B signal peptide polymorphism had a similar effect on Apo-B-related parameters as seen in Strasbourg. No significant associations were observed in the Haute-Garonne population where the risk of myocardial infarction is three times lower than in Belfast. In all three populations, the average Lp(a) levels were consistently different among Apo B signal peptide genotypes. These data implicate the Apo B signal peptide in determining some of the risks of myocardial infarction in these populations. Regardless of the exact mechanism, the Apo B signal peptide is an important candidate locus for the study of potentially atherogenic lipid variants.

Adult↗

Lipoprotein metabolism in marasmic children of northern Mauritania.

Lipid metabolism in marasmus has been poorly studied compared with that in kwashiorkor. Published studies show normal or high plasma triglycerides and low cholesterol concentrations. We studied some plasma lipid indexes, including total, HDL, and LDL cholesterol; triglycerides; apolipoproteins A-I, A-II, B, C-III, and E; and lipoprotein particles containing apo A-I, apo A-I and A-II (Lp A-I:A-II) Lp C-III:B, and Lp E:B in Mauritanian marasmic children compared with a control group. We found in patients low total, HDL, and LDL cholesterol and normal Lp A-I concentrations, which suggest that the cholesterol reverse transport system is not altered. We observed normal triglyceride concentrations and significantly increased Lp C-III:B and Lp E:B, which are triglyceride-rich particles. These data suggest that the marasmic state led to quantitative and structural modifications of the triglyceride-rich lipoproteins, defined by their apolipoprotein composition, and was probably related to undercatabolism.

Anthropometry↗

Isolation and characterization of two sub-species of Lp(a), one containing apo E and one free of apo E.

Lipoprotein Lp(a) was isolated by immunoaffinity chromatography using anti apolipoprotein B and anti apolipoprotein (a) immunosorbents. Besides apolipoproteins (a) and B, this fraction was shown to contain apolipoproteins C and E. Therefore, it was decided to further purify this crude Lp(a) into particles containing apolipoprotein E and particles free of apo E, using chromatography with an anti apolipoprotein E immunosorbent. Lp(a), free of apolipoprotein E was cholesterol ester rich and triacylglycerol poor and was found mainly in the LDL size range. In contrast, Lp(a) containing apolipoprotein E was triacylglycerol rich and was distributed mainly in the VLDL and IDL size range. Binding of these two fractions, one containing apo E and one free of it, to the apo B/E receptor of HeLa cells was studied. Both fractions bound to the receptor but the one containing apo E had a better affinity than the one free of apo E. Further studies are needed to identify the clinical importance of these two different entities.

Apolipoproteins↗