TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to the inhibition of P. falciparum growth in human blood.

After invading red blood cells (RBCs), Plasmodium falciparum (Pf) can export its own proteins to the host membrane and activate endogenous channels that are present in the membrane of RBCs. This transport pathway involves the Voltage Dependent Anion Channel (VDAC). Moreover, ligands of the VDAC partner TranSlocator PrOtein (TSPO) were demonstrated to inhibit the growth of the parasite. We studied the expression of TSPO and VDAC isoforms in late erythroid precursors, examined the presence of these proteins in membranes of non-infected and infected human RBCs, and evaluated the efficiency of TSPO ligands in inhibiting plasmodium growth, transporting the haem analogue Zn-protoporphyrin-IX (ZnPPIX) and enhancing the accumulation of reactive oxygen species (ROS). TSPO and VDAC isoforms are differentially expressed on erythroid cells in late differentiation states. TSPO2 and VDAC are present in the membranes of mature RBCs in a unique protein complex that changes the affinity of TSPO ligands after Pf infection. TSPO ligands dose-dependently inhibited parasite growth, and this inhibition was correlated to ZnPPIX uptake and ROS accumulation in the infected RBCs. Our results demonstrate that TSPO ligands can induce Pf death by increasing the uptake of porphyrins through a TSPO2-VDAC complex, which leads to an accumulation of ROS.

An epidemic of a "new" haemorrhagic disease in infants attributable to talcum powder contaminated with warfarin in Ho-Chi-Minh Ville (Vietnam).

In August 1981, pediatric hospitals in Ho-Chi-Minh Ville (Saigon) began to report numerous cases of a haemorrhagic syndrome in infants. A collaborative study with a French epidemilogist began on September 24, 1981, with the aim of finding the cause of this "new" haemorrhagic disease. After having excluded the hypothesis of a viral or bacterial infection, a retrospective study, using questionnaires with 83 items, concerning products of hygiene and nutrition and living conditions, was undertaken. This epidemiological investigation showed this phenomenon was caused by an anticoagulant contained in talcum powder. Analysis of the talcum powders found warfarin; the concentrations ranged between 1.7% and 6.5%. This dramatic episode (741 cases with 177 deaths) ended when the contaminated talc was withdrawn from circulation. The hypothesis of accidental contamination or use of warfarin in lieu of a perfuming agent must be rejected. Accidental addition of a rat-killer seems highly improbable and the possibility of intentional and malevolent adulteration is now under study. An experimental study of hemostasis in two baboons was carried out, using dermal application of the contaminated talc powder. The intoxicated animal died on the 5th day with severe vitamin K deficiency. This accident together with the animal study, shows the transcutaneous uptake of the anticoagulant, which could be of considerable importance in toxicology and in pharmacokinetics.

Seroepidemiological survey of toxoplasmosis in La Guadeloupe, French West Indies.

A random survey of 1% of the total population of La Guadeloupe, French West Indies, for toxoplasmosis was carried out. Blood specimens from 3,238 individuals were collected on filter paper strips and tested for Toxoplasma antibodies by the fluorescent antibody technique. Sixty percent were positive. A gradual increase in positivity with increasing age, and high prevalence in children (50% in the 6- to 10-year age group) were observed. No differences were found among the different ethnic groups, nor among persons in different occupations. Economic status showed a highly negative correlation with antibody prevalence rates. The infection rate was not higher in individuals who consumed raw or undercooked meat, and no differences in antibody prevalence related to the sources of meat were observed. The seropositivity rates varied over a wide range (40-76%) according to the locality; higher Toxoplasma antibody rates were found in areas with higher rainfall, and toxoplasmosis prevalence rates correlated positively with mean annual rainfall but not with altitude or with rural or urban residence. A significant difference was observed between seropositivity rates when people living in houses with or without cats were compared. A higher prevalence of hookworm and Strongyloides infections--considered as evidence of closer contact with moist soil--were found in children with Toxoplasma antibodies than in age-adjusted control children without such antibodies. These results provide evidence that meat plays a negligible role in the transmission of Toxoplasma to man, and support the hypothesis that oocysts shed in cat feces are the almost exclusive mode of human infection in Guadeloupe.

[Incident of intestinal parasitosis in Martinique]. / Prévalence des parasitoses intestinales en Martinique.

A survey of intestinal parasitosis was conducted in Martinique by INSERM in 1978. The survey used a stratified sample of 823 households from the general population. The most prevalent parasitosis are: schistosomiasis 19%; ancylostomiasis 18%; trichuriasis 37%; ascaridiasis 7%; strongiloidiasis 3%. 70% of the 5 to 15 age group carries at least 1 parasite. The prevalence of trichuriasis, ascaridiasis and giardiasis is greatest in the 5 to 15 age group, Ancylostomiasis concerns mostly the 15 to 30 age group. Schistosomiasis, was most prevalent in adults over 30 years of age. Prevalence of parasitosis in rural regions is double that of urbanised regions. Schistosomiasis mostly occurs in the north. Ascaridiasis in the north-east. Rainfall and housing status, each influence on the rates of infestation.

[Results of a comparative therapeutic trial of single-dose treatment of non-complicated acute male gonorrhea]. / Résultats d'un essai thérapeutique comparatif pour le traitement en une prise de la gonococcie masculine aiguë non compliquée.

A single dose treatment trial with: spectinomycine 2 g, ampicilline + probenecide 3.5 g + 1 g, thiamphenicol 2.5 g, minocycline 300 mg was undertaken. Three teams were involved, epidemiologists clinicians, microbiologists, 636 patients were included, 483 resumed for control. A negative culture on the third day was considered a success. Failure rates were: spectinomycine 4%, ampicilline-probenecide 3%, thiamphenicol 4%, minocycline 3%. No significant difference was noted between the four rates. The delay of clinical cure was 1.98 days for spectinomycin, 1.87 days for ampicilline - probenecide, 2.16 days for thiamphenicol and 2.12 for minocycline without significant difference. When side effects were analysed, 10% of the patients reported asthenia without difference between the four treatments. Thiamphenicol is responsible for diarrhea 28%, P less than 0,01 minocycline more significantly responsible for guidiness 13%, P less than 0,001, and 18% treated by spectinomycine complained of pain at the time of injection. The antibiotics MIC's are studied. After the analysis of the results, the cost, and the resistances, one treatment was selected.

Epidemic of haemorrhagic disease in Vietnamese infants caused by warfarin-contaminated talcs.

In August, 1981, paediatric hospitals in Ho Chi Minh City (formerly Saigon), Vietnam, began to report cases of a haemorrhagic syndrome in infants. The cause of this haemorrhagic phenomenon was identified as talcum powder contaminated with the anticoagulant warfarin. Analysis of talcum powders revealed warfarin in concentrations between 1.7% and 6.5%. 741 cases were detected and 177 patients died. The possibility of accidental contamination or substitution of a perfuming agent by warfarin can be rejected. In an experiment with two baboons, the animal exposed to the contaminated talc died five days later from haemorrhage. The accident and the animal study demonstrate the significant transcutaneous uptake of the anticoagulant.

Hexachlorophene and the central nervous system. Toxic effects in mice and baboons.

A study on hexachlorophene encephalopathy in mice and baboons is reported. By light microscopy, a severe spongiform lesion of the central nervous system (CNS) was localized in the white matter, without myelin breakdown or cellular reaction. By electron microscopy, the myelin alteration was characterized by wide intralamellar spaces or "splitting" developed in the intraperiod line of compact sheaths. The acute changes described were induced by administration of the drug by the digestive or cutaneous routes at various dosage levels in an aqueous solution or in talcum powder. The toxic effects depended on the age of the animals, the survival times and the concentrations of hexachlorophene, i.e., 6%, 3%, and 0.5%. The findings are compared with previous reports on the neurotoxicity of hexachlorophene and other chemicals in human and experimental animals. Hexachlorophene cannot be recommended for use in young infants because of its neurotoxicity in very low doses as demonstrated in the present report.

[Epidemiology of Brucellosis. Trial evaluation of the incidence of clinical and infraclinical forms (author's transl)]. / Epidémiologie des brucelloses. Essai d'évaluation de l'incidence des formes cliniques et infracliniques.

The incidence of clinical and infraclinical human brucellosis was estimated by survey undertaken in 1976 on a representative sample of the population of the Vaucluse (France) district. It is shown that, by combining research of late hypersensitivity and serologic tracking in 2084 individuals, the incidence of diagnosed clinical brucellosis, in the Vaucluse district is at least 3 to 5 times more important than the incidence evaluated by the official notifications, and that there are 10 times more infraclinical or non diagnosed brucellosis than diagnosed brucellosis. The results show the need of triple investigation by interview, serology and hypersensitivity test (complementarity of the three technics) so as to evaluate the true morbidity of this anthropozoonosis.

Experimental hexachlorophene encephalopathy in mice and baboons: light and electron microscopic study.

An experimental study on acute Hexachlorophene (HCP) neurotoxicity is reported in mice and baboons: - by light microscopy, a severe spongiform lesion of the central nervous system is localized in the white matter without myelin breakdown or cellular reaction; - by electron microscopy, the myelin alteration is characterized by the presence of vacuolation of "splitting" in the intralamellar spaces of compact sheaths; myelinated axons are occasionally involved. The changes described are discussed according to various reports on HCP neurotoxicity in humans and experimental animals. The effects of this chemical agent on the central nervous system is related to the percentage of HCP in talcum powder or solution for topical use. The toxicity of very low dosage level is demonstrated in baboons. Therefore HCP use cannot be recommended for young infants.

[Present sensitivity of Neisseria gonorrhoeae in the Paris area. Results of a comparative therapeutic trial]. / La sensibilité actuelle de Neisseria gonorrhoeae en région parisienne. Résultats d'un thérapeutique comparé.

From September 1978 to September 1979, the Authors determined the M. I. C. of 16 antibiotics against 420 Neisseria gonorrhoeae strains collected in Paris area, with standard gel dilution technic. These strains remain susceptible to the greatest proportion of antibiotics tested, except streptomycin. It has been noted, however, that sensibility of a certain percentage of strains, has decreased for penicillins, cyclins, macrolides. Some strains producing beta-lactamase has been identified. Authors compared results given by the gel dilution method to those given by the diffusion or so-called "disc" method. This shows no correlation between radius of inhibition and M. I. G., with no reliable criteria to estimate the area of inhibition. Also, four protocols for therapy were followed: spectinomycin, ampicillin-probenocid, thiamphenicol, minocyclin. The patients were surveyed by physical examination and bacteriological tests. No statistically significant differences could be noted between these four protocols. However, considering the size of the samples, it is not possible to conclude. The authors reassess the necessity to survey the drug-sensitivity of Neisseria gonorrhoeae strains, in each geographical area, following an internationally agreed method. They also conclude to the necessity to compare in vitro sensitivity tests with therapeutic schemes suggested by usual sensitivity to main antibiotics.