Treponema species enrich the gut microbiota of traditional rural populations but are absent from urban individuals.

There is a significant gap in our knowledge of the microbe-host relationship between urban and traditional rural populations. We conducted a large-scale study to examine the gut microbiota of different traditional rural and urban lifestyles in human populations. Using high-throughput 16S ribosomal RNA gene amplicon sequencing, we tested urban French, Saudi, Senegalese, Nigerian and Polynesian individuals as well as individuals living in traditional rural societies, including Amazonians from French Guiana, Congolese Pygmies, Saudi Bedouins and Algerian Tuaregs. The gut microbiota from individuals living in traditional rural settings clustered differently and presented significantly higher diversity than those of urban populations (p 0.01). The bacterial taxa identified by class analysis as contributing most significantly to each cluster were Phascolarctobacterium for traditional rural individuals and Bifidobacterium for urban individuals. Spirochaetae were only present in the gut microbiota of individuals from traditional rural societies, and the gut microbiota of all traditional rural populations was enriched with Treponema succinifaciens. Cross-transmission of Treponema from termites or swine to humans or the increased use of antibiotics in nontraditional populations may explain why Treponema is present only in the gut microbiota of traditional rural populations.

[Preliminary results about loiasis in the district of Likouala in the Republic of the Congo]. / Résultats préliminaires sur la situation de la loase dans le département de la Likouala, en république du Congo.

The authors report results of a prospective study to assess the prevalence of loiasis in populations older than 18 years in two villages of the Likouala district in the Congo: the study took place during a visit to Lopola in 2012 and to Lopola and Lombo in 2013. The prevalence rate was 20%. Loa loa carriers were treated with diethylcarbamazine citrate and celestamine.

[Report of the 4th International Conference on Envenomations by Snakebites and Scorpion Stings in Africa, Dakar, April 25-29, 2011]. / 4(e) Conférence internationale sur les envenimations par morsures de serpent et piqûres de scorpion en Afrique : Dakar, 25-29 avril 2011.

The authors present a summary of the proceedings and the recommendations of the Fourth International Conference on Envenomations by Snakebites and Scorpion Stings in Africa, held from 25 to 29 April 2011 in Dakar. After a two-day workshop for Senegalese health personnel on the most relevant aspects of the management of envenomations, about 270 participants met to share their experiences in the field. Nearly a hundred oral and poster presentations were made on the epidemiology of snakebites and scorpion stings in Africa, the composition and action of venoms and the manufacture and use of antivenoms. The last day was devoted to an institutional debate involving experts, representatives of national health authorities and concerned professionals (physicians, pharmacists, nurses and traditional healers) as well as members of the pharmaceutical industry to discuss and elaborate a set of recommendations. It was agreed that it is necessary to improve knowledge of the epidemiological situation by case reporting. Quality control of antivenoms and procedures for their registration at the level of national health authorities should aim at improving the distribution of safe and effective antivenoms in peripheral health centers for the better assessment of victims. It was also recommended that adequate training should be provided for health personnel in all aspects of medical management of envenomations. Equitable distribution of funding and the establishment of a network of African experts were also discussed in the conference.

[Report of the 3rd International Conference on Envenomations in Africa]. / Troisième Conférence internationale sur les envenimations en Afrique. Brazzaville, 15-17 novembre 2007.

The 3rd International Conference on Envenomations was held in Brazzaville from 15 to 17 November; 2007. At this meeting, updating of epidemiological and treatment information on envenomations in Africa were presented. A round table concluded the conference drawing contributors' main recommendations. One of these recommendation pointed out the need to treat the problem of envenimations at a regional level by creating a group of experts in charge of considering the priorities as well as identifying relevant strategies of management, ensuring the plea and finding the financing.

[Situation of the envenomations by snakebites in Congo-Brazzaville: epidemiological, clinical and therapeutic approaches]. / Situation des envenimations par morsure de serpent au Congo-Brazzaville: approches épidémiologique, clinique et thérapeutique.

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.

Activity of a specific inhibitor, gefitinib (Iressa, ZD1839), of epidermal growth factor receptor in refractory non-small-cell lung cancer.

BACKGROUND: Gefitinib (Iressa(TM), ZD1839) is an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Phase I studies showed that it is well tolerated, with evidence of tumor regression in patients with advanced non-small-cell lung cancer (NSCLC). Therefore, we aimed to assess the antitumor activity and tolerability of gefitinib in a series of patients with previously treated, advanced NSCLC, as a part of a compassionate use program. PATIENTS AND METHODS: To be eligible, all patients were required to have histologically or cytologically proven advanced or metastatic NSCLC, prior chemotherapy with at least one cisplatin-containing chemotherapy regimen or contraindication to cytotoxic drugs, Eastern Cooperative Oncology Group performance status < or =2, and adequate hematological, renal and hepatic parameters. All patients provided signed informed consent. Patient re-evaluation was performed every 4-6 weeks. RESULTS: Seventy-three consecutive patients were enrolled. Response rate, including complete and partial response, was 9.6%; an additional 43.8% of patients achieved stable disease, for an overall disease control of 53.4%. EGFR1 status was evaluated by immunocytochemistry in 25 patients. According to EGFR1 immunoreactivity all responses were observed with medium/strong imunoreactivity while three out of four responses were observed in high expressive patients. Median survival for all patients was 4 months while it reached 6 months for patients with disease control. The 1-year survival rate was 13.1% for the entire series and 23.2% for patients with disease control. Non-hematological toxicity was generally mild. CONCLUSION: Gefitinib has promising activity with a good toxicity profile in patients with progressive NSCLC who have received one or two prior chemotherapy regimens. A possible relationship within response and EGFR1 expression is suggested.

[Study of the protein profile of the Adélé tribe of Togo]. / Etude du profil protéique des Adélé du Togo.

Plasma proteins provide precise information about the physiological status of an individual. In this study, we compared the plasma protein profiles of 168 individuals from the Adélé ethnic group, from an isolated rural area of Togo, with those of 159 individuals from an urban population from the capital, Lomé. The Adélé villages are located in the Atakora mountains. The subjects were volunteers, all apparently healthy and aged between 18 and 65 years. We separated serum proteins by electrophoresis and identified proteins specific for nutritional, inflammatory and immune status. The Adélé significantly higher total serum protein concentrations than the urban individuals, with higher concentrations of a1 globulins (2.35 +/- 0.57 g/L versus 1.94 +/- 0.52 g/L) and g globulins (22.19 +/- 5.67 g/L versus 16.98 +/- 5.23 g/L) and lower concentrations of b globulins (6.83 +/- 1.56 g/L versus 7.34 +/- 1. 52 g/L). The Adélé also had lower plasma concentrations of albumin (41.91 +/- 5.74 g/L versus 44.56 +/- 6.32 g/L), tranferrin (2.5 +/- 0.52 g/L versus 3.03 +/- 0.6 g/L), haptoglobin (0.57 +/- 0.59 g/L versus 1.32 +/- 0.89 g/L) and IgA (2.3 +/- 0.89 g/L versus 2.88 +/- 1.12 g/L) and higher plasma concentrations of orosomucoid (0.85 +/- 0.26 g/L versus 0.69 +/- 0.27 g/L); IgG (25.3 +/- 7.11 g/L versus 21. 79 +/- 6.5 g/L) and IgM (4.25 +/- 2.83 g/L versus 2.25 +/- 1.0 g/L). The data obtained for the Adélé and urban populations were similar to those obtained for European populations except for IgM (higher in the Adélé than in the urban and European populations), IgG and CRP (higher for the Adélé and urban populations than for European populations). Nutritional status, as estimated by albumin and transferrin concentrations, was higher in the urban population of Lomé than in the Adélé population but the Adélé population suffered no malnutrition problems. These results are consistent with those of a previous study, using apo A-I concentrations as an index of nutritional status. Apo A-I has also been shown to be a reliable indicator of nutritional status, as prealbumin concentration alone is sufficient for the early diagnosis of protein malnutrition. The very high concentrations of plasma CRP obtained indicate the presence of an inflammatory syndrome in the Adélé and urban populations, as this protein is the first acute phase protein to be detected. However, the orosomucoid concentrations obtain-ed provide no evidence of significant inflammation. The high affinity of haptoglobin (Hp) for hemoglobin (Hb) results in the formation of soluble Hp-Hb complexes, reducing the value of Hp as a marker of the acute phase of inflammation. The frequency os sickle cell disease was higher in the Adélé population than in the urban population (10-25% versus 2-6%). Hemoglobinopathies are correlated with haptoglobin concentration and thus plasma haptoglobin concentration was lower in the Adélé population than in the urban population. The plasma concentrations of a1-antitrypsin in this study were similar to those reported for Europeans. The plasma concentration of protease inhibitors, such as a1-antitrypsin, increased as protease levels increased. These data confirm that the Adélé and urban populations suffer no disease due to high levels of protease release into the bloodstream. They also show that a1-antitrypsin is of some value as an acute phase marker protein. The acute nature of the inflammatory syndrome (as assessed by CRP concentration) in the Adélé and urban populations was confirmed by the hyperglobulinemia (high levels of production of IgM and IgG antibodies) observed in these populations. The Adélé and Lomé urban populations live in a tropical environment in which they are continuously in contact with infectious agents. This results in repeated stimulation of the immune system in both these populations. This study of plasma proteins in the Adélé provides insight into the physiological conditions of this ethnic group, w

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.

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.

Natural infection of chimpanzees with new lentiviruses related to HIV-1/SIVcpz.

To determine newly identified lentiviruses, termed simian immunodeficiency virus (SIV)cpz97CG4 and SIVcpz97CG6, from two wild-captured juvenile brother chimpanzees in the Republic of Congo, subgenomic pol (integrase, 288 bp), 5'tat/rev-env Cl (including vpu, 354 bp) and env (C2-C4, 544 bp) gene fragments were amplified and sequenced. The analysis revealed significantly discordant phylogenetic positions of SIVcpz97CG in each genomic region. In the trees derived from partial env sequences (V3), both SIVcpz strains clustered in human immunodeficiency virus type 1 (HIV-1) subtype A. However, in the trees derived from partial pol (integrase) and 5'tat/rev-env C1 (including vpu) sequences, they clustered independently from any of the known HIV-1 subtypes. Especially, in the 5'tat/rev-vpu tree, they branched before the root of HIV-1 group M. These findings suggest that these Congolese SIVcpz genomes are mosaic, probably due to a recombinational event in the recent past, and it provides evidence for a rather recently occurring cross-species transmission between humans and chimpanzees.

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.

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.

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.

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.

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.

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 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.

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.