[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.

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.

[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.

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.

[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.

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.

Lowering of HDL2-cholesterol and lipoprotein A-I particle levels by increasing the ratio of polyunsaturated to saturated fatty acids.

The protective role of high-density lipoproteins (HDLs) has been attributed to the subfractions HDL2 (according to the density) and lipoprotein A-I (LpA-I) (according to the composition in apolipoproteins). We investigated the effect of a high ratio of polyunsaturated to saturated fatty acids (P:S) on these subfractions in a homogeneous group of young adult males. Two prescribed diets were consumed successively at the subjects' homes for 3 wk each in a random order; one diet contained 70 g butter (P:S 0.2, diet B), the other contained 70 g sunflower margarine (P:S 1.1, diet M). Total calorie, fat, and cholesterol intakes were similar for the two diets. Cholesterol and apolipoprotein B in serum and in low-density lipoproteins (LDLs) were lower with diet M than with diet B. However, significant decreases in protective subfractions of HDL, HDL2, and LpA-I were observed. This undesirable effect of the diet with a high P:S could cancel the benefits of lowering the LDL-cholesterol concentrations.

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.

n-3 polyunsaturated fatty acids raise low-density lipoproteins, high-density lipoprotein 2, and plasminogen-activator inhibitor in healthy young men.

The effects of a moderate supplementation in n-3 polyunsaturated fatty acids (PUFAs) were investigated in 36 young healthy adult males. Factors investigated were lipoprotein (including HDL subfractions and apolipoproteins) and hemostasis indexes, assessed by platelet aggregation and plasminogen-activator-inhibitor (PAI) activity. Fat-controlled diets were prescribed, one with and one without a fish-oil supplement (control diet), successively during 3 wk in random order. Total calorie, fat, and cholesterol intakes were similar in the two diets. Triglycerides in serum and very-low-density lipoproteins were lower and high-density-lipoprotein 2 cholesterol was higher with the n-3 PUFA-supplemented diet. These effects as well as a significant decrease in platelet aggregation can be considered beneficial in terms of cardiovascular risk. However, significant increases in low-density-lipoprotein cholesterol and PAI activity occurred and were correlated. This latter effect could be detrimental.

Lipoprotein particle analysis comparing simvastatin and fenofibrate.

This study compares the effects of fenofibrate and simvastatin in primary hypercholesterolemia, with particular regard to lipoprotein particles, as defined by their apolipoprotein composition: LpAI, LpAII: AI, LpE:B, LpCIII:B. This was a double-blind study in which patients were randomized to 2 groups, one receiving simvastatin 20 mg once daily and the other receiving fenofibrate 200 mg b.i.d., if their total cholesterol and their LDL cholesterol remained above 7.60 mmol/l (300 mg/dl) and 4.95 mmol/l (195 mg/dl) after a 4-week placebo period. Simvastatin dosage was doubled at the end of 6 weeks of therapy if the LDL-cholesterol level remained above 3.55 mmol/l (140 mg/dl). Analyses were done after 6 and 10 weeks of therapy. Apolipoprotein AI was increased significantly only at week 10 with fenofibrate (+7.4%). Simvastatin had a more pronounced effect than fenofibrate on apolipoprotein B. There was a significant difference between drugs at weeks 6 and 10. No change was observed in the LpAII:AI level with simvastatin, whereas fenofibrate increased these particles quite significantly (+13.9 and +22.3%). The drugs had opposite effects on LpAI (+2.5 and +5.6% with simvastatin; -12.8 and -15.1% with fenofibrate). LP E:B (-33.0 and -40.8% with simvastatin; -53.8 and -52.2% with fenofibrate) and LpCIII:B (-23.8 and -31.8% with simvastatin; -35.1 and -43.5% with fenofibrate) were decreased by both drugs, but fenofibrate was significantly more effective in reducing these particles than simvastatin at week 6. This study suggests that both drugs led to different structural modifications of the lipoproteins, which would not be revealed by total apolipoprotein analysis. These differences are probably related to the mechanisms of action of these drugs.

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.

Effect of pravastatin, an HMG CoA reductase inhibitor, and cholestyramine, a bile acid sequestrant, on lipoprotein particles defined by their apolipoprotein composition.

This study compares the effects of cholestyramine (16 g/d) and pravastatin (40 mg/d) on lipoprotein particles defined by their apolipoprotein composition (Lp A-I, Lp A-II:A-I, Lp E:B, and Lp C-III:B). Analysis was performed after 4, 8, and 12 weeks of therapy. Low-density lipoprotein (LDL) cholesterol decreased by 25.1% to 35.0% with cholestyramine and 26.2% to 30.7% with pravastatin, while triglycerides decreased slightly with pravastatin therapy and increased slightly during cholestyramine administration. The fall in cholesterol was mainly due to a decrease in very-low-density lipoprotein (VLDL) and LDL cholesterol; high-density lipoprotein (HDL) cholesterol increased. Apolipoprotein B was reduced dramatically (by 21.7% to 30.5% with cholestyramine and 27.7% to 37.4% with pravastatin). No significant effect on apolipoproteins C-III and E was observed with cholestyramine, while pravastatin reduced these parameters slightly. Apolipoprotein A-I increased during therapy with both drugs, while apolipoprotein A-II was slightly decreased. Although the drugs had nearly the same effects on plasma lipids, their influence on lipoprotein particles defined by their apolipoprotein composition was substantially different. Lp A-II:A-I was increased by both drugs (+8.1% to +41.2% for cholestyramine and +7.2% to +32.6% for pravastatin). Lp A-I was also increased with both drugs, but cholestyramine had a more constant and pronounced effect than pravastatin (+15.1% to +21.7% for cholestyramine and +1.7% to +13.0% for pravastatin). Lp E:B and Lp C-III:B were consistently decreased by pravastatin (-10.2% to -36.5% for LP E:B and -7.2% to -20.9% for Lp C-III:B), while cholestyramine had variable effects on these particles.(ABSTRACT TRUNCATED AT 250 WORDS)

High-density lipoprotein particles in octogenarians.

High-density lipoprotein (HDL) particles exhibit considerable heterogeneity, specifically in apolipoprotein (apo) composition. Thus, apo A-I, the major protein of HDL, is present in two types of particles: one species contains both apo A-I and apo A-II (Lp A-I/A-II) while in the other (Lp A-I), apo A-II is absent. We used the hypothesis that octogenarians, who survived periods in life when the incidence of coronary heart disease (CHD) is very high, have several protective factors. We compared HDL-cholesterol (HDL-C), HDL2-cholesterol (HDL2-C), HDL3-cholesterol (HDL3-C), apo A-I, and apo A-II in octogenarians and younger control subjects smoking less than 10 cigarettes/d and not taking drugs known to affect lipid metabolism. Using a new procedure, we also compared the levels of Lp A-I and Lp A-I/A-II. The cholesterol content of total HDL was similar in octogenarian and control (38 +/- 8 years) men while HDL2-C was higher and HDL3-C, apo A-I, and A-II were lower in octogenarian than in control men. In women, the level of HDL-C and apo A-I was similar in premenopausal and octogenarian subjects but higher in postmenopausal women than in octogenarians, while HDL2-C and apo A-II were similar in the three groups. In contrast, HDL3-C was higher in the two groups of control women (premenopausal and postmenopausal) than in octogenarians. However, Lp A-I was significantly elevated in octogenarian men and women (men: 61 +/- 14 mg/dL; women: 70 +/- 14 mg/dL) by comparison with younger control subjects (men: 48 +/- 12 mg/dL; premenopausal women: 53 +/- 11 mg/dL; postmenopausal women: 63 +/- 19 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)

A multicenter comparison of the effects of simvastatin and fenofibrate therapy in severe primary hypercholesterolemia, with particular emphasis on lipoproteins defined by their apolipoprotein composition.

This multicenter, double-blind, randomized study was designed to compare the effects of simvastatin (20 mg/d and 40 mg/d) and fenofibrate (400 mg/d) on plasma lipids, lipoproteins, apolipoproteins (apo), and lipoprotein particles defined by their apo composition (Lp A-I, Lp A-II:A-I, Lp E:B, Lp C-III:B) in primary hypercholesterolemia. After 6 and 10 weeks of therapy, both drugs lowered plasma cholesterol, low-density lipoprotein (LDL) cholesterol, and apo B. The effect on LDL and apo B was significantly more pronounced for simvastatin (P = .01). Simvastatin increased Lp A-I, but did not change Lp A-II:A-I, while fenofibrate decreased Lp A-I and increased Lp A-II:A-I. Lp E:B and Lp C-III:B were decreased with both drugs, but fenofibrate was significantly more effective in reducing these particles than simvastatin. This study demonstrates that both drugs have beneficial effects on the parameters positively or negatively correlated with the atherosclerotic risk, with simvastatin being more effective in reducing some of them. These results suggest that the drugs led to different structural modifications of the lipoproteins, which would not be revealed by examination of lipoprotein density classes. These differences are probably related to the different mechanisms of action of the agents.

Black-white differences in serum Lp(a) lipoprotein levels.

Serum Lp(a) lipoprotein was determined in 81 black and 81 white healthy men and women matched for sex and age. The results show a highly significant increase of Lp(a) concentrations in blacks as compared to whites, and confirm the notion that Lp(a) lipoprotein levels are race-dependent. Whether high values of Lp(a) play an atherogenic role in blacks remains to be established in further studies.

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.

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.

The increased plasma Lp(a): B lipoprotein particle concentration in angina pectoris is not associated with hypofibrinolysis.

The structural homology between plasminogen and apolipoprotein (a), the specific glycoprotein of Lp(a) lipoprotein, raises the possibility of a relationship between this lipoprotein and the plasma fibrinolytic system. The present study examines this proposal by studying 66 patients with angina pectoris. As compared to normal controls, the patients had raised concentrations of Lp(a): B lipoprotein particles. No correlation was found between circulating Lp(a): B and the fibrinolytic system. The pathogenic role of Lp(a): B lipoprotein seems therefore not mediated by its effect on the plasma fibrinolytic system.

Serum amyloid A concentrations in giant-cell arteritis and polymyalgia rheumatica: a useful test in the management of the disease.

A prospective clinical study of 23 patients with giant-cell arteritis (GCA) and/or polymyalgia rheumatica (PMR) was undertaken in order to assess the behaviour of the non-specific markers of the disease activity, the erythrocyte sedimentation rate (ESR) and other acute phase markers, particularly the C-reactive protein (CPR) and serum amyloid A apolipoprotein (apo SAA) levels during induction of disease remission by prednisone therapy, and possible further recurrence of GCA and/or PMR. The apo SAA measurement is more sensitive than the CRP measurement in determining disease activity (97% and 61%, respectively). The specificity of apo SAA is greater than ESR in the determination of inactive disease (86% and 77%, respectively). In some cases with clinically active disease the ESR and CRP were normal, whereas the apo SAA was always elevated. We conclude that the apo SAA measurement in combination with clinical data and other laboratory parameters may be useful in the management of GCA and/or PMR.