Differences in hypolipidaemic effects of two statins on Hep G2 cells or human hepatocytes in primary culture.

1. The objective of this study was to compare in cultured human hepatocytes or Hep G2 cells, changes in the fate of unesterified low density lipoprotein (LDL)-cholesterol induced by crilvastatin, a new cholesterol lowering drug and a reference statin, simvastatin. 2. The experiments were carried out for 20 h, each well contained 4.2 x 10(5)/cm2 Hep G2 cells or 0.5 x 10(5)/Cm2 human hepatocytes, 130 microM ursodeoxycholate, 0.68 microCi or 1.59 microCi unesterified human [14C]-LDL-cholesterol, crilvastatin or simvastatin at 0 or 50 microM (both cell types) or 300 microM (Hep-G2 cells). Incubation with the two drugs resulted in increased amounts of unesterified [14C]-LDL-cholesterol taken by the two cell types, compared to control. 3. Crilvastatin 50 microM led to significantly higher quantities of [14C]-glyco-tauro-conjugated bile salts, compared to simvastatin. Statins reduced the apo B100 level secreted by the two cell types (simvastatin) or human hepatocytes (crilvastatin). Crilvastatin enhanced both the level of apo A1 secreted by the Hep G2 cells and the level of APF, a high density lipoprotein (HDL) and biliary apoprotein. 4. Crilvastatin not only acts by stimulating LDL-cholesterol uptake by hepatocytes, but also by enhancing the catabolism of LDL-cholesterol in bile salts and probably by stimulating HDL and/or bile component secretion. Such a mechanism was not previously described for HMG CoA reductase inhibitors. Our results on APF show that this apoprotein could be considered also as an indicator of changes in bile and/or HDL compartments. 5. The human hepatocyte model appeared to be a suitable and relevant model in the pharmacological-metabolic experiments carried out in this study. It led to more consistent data than those obtained with Hep G2 cells.

[Orphan drugs: problem of public health and economic stakes]. / Les médicaments orphelins: problème de santé publique et enjeux économiques.

Orphan drugs (OD) qualify as drugs scientifically viable but not viable from an economic point of view either because the number of patients who might benefit is too small or because the populations concerned are too poor to afford the drugs. Sick people who could be treated by OD and their families have been fighting for years to induce authorities in charge of health to set up a programme to stimulate research into new treatment for rare diseases. The United States, initiated work in order to confer status on OD leading to the Orphan Drug Act in 1983. It defined the conditions for attribution of the OD status and also made attractive proposals to pharmaceutic industries in order to improve their development. More recently, in 1993, Japan took similar decisions, while the European Union and France are also on the way, as recent meetings of European ministers of health show. In contrast, developing countries are still excluded from medical research as very few tropical diseases have treatment. Legislation for OD, first planned to make up for the high costs of research and development, proved its efficiency. But ODs must move to a new status as some are now becoming the object of important economic stakes.

[Khat: from traditional usage to risk of drug addiction]. / Le khat: de l'usage traditionnel au risque toxicomaniaque.

In much of East Africa and the Arabian Peninsula, the leaves of the qat tree (Catha edulis Forsk) are highly prized for their euphoric effects. Use is deeply anchored in regional customs and traditions. Once controversial, the chemical properties of qat are now well-documented; the active agent responsible for the physical and mental effects observed when the leaves are chewed is cathinone or alpha-aminopropiophenone. According to the definition of the World Health Organization, qat is not classified as an inevitably addictive drug. However recent reports of psychosis related to qat abuse in Great Britain and the United States have raised new alarm in the Narcotics Commission of the United Nations. Should qat be prohibited? International law on this issue is currently highly ambiguous. Importation of qat is illegal in France as in Switzerland, but legal in the United States and Great Britain as in most African countries.

[Evaluation of two methods for detecting HBS antigen in serum (author's transl)]. / Comparaison de deux méthodes de détermination de l'antigène HBS dans le sérum.

Two methods of third generation are described: the inverse passive agglutination test and the immunoenzymologic method of the ELISA test. From 500 serum tests, it is suggested that ELISA test has a sensibility of 5,2 p. 100 superior to that of the inverse passive agglutination test which, in addition gives 1 p. 100 of false positive results. It must be noted that the ELISA test requires a very careful technical skill.

[Determination of some usual and frequent values in clinical biochemistry in a Polynesian population sample. Comparison with French reference values]. / Détermination de quelques valeurs usuelles fréquentes en biochimie clinique dans un échantillon de populations polynésiennes. Comparaison avec les valeurs de référence françaises.

The normal values for glucose, urea, uric acid and creatinine in serum have been determined in a selected Polynesian population. The results are similar for obese or non-obese subjects as well as for the people living in Papeete. A comparison between these data and the French standard values reveals significant differences in regard to glucose, urea and uric acid.

[Poisoning by ingestion of ditakh (Senegal)]. / Intoxication par ingestion de ditakh (Sénégal).

In regard to food poisoning as a result of the eating of non edible fruit, we have noticed the particular case of a well-known fruit in Senegal: the DITAKH (woloff local name). It would appear that some trees produce poisonous fruit and others perfectly safe edible fruit. Following a description of the habitat and morphological and physical characteristics, the authors wonder whether or not they should consider, because of the edible/non edible characteristics of Detarium, the existence of two different species or two different varieties.

[Note on the detection of hemoglobin lepore in a Senegalaise (author's transl)]. / A propos de la découverte d'une hémoglobine Lepore chez un Senegalais.

After reviewing briefly the characteristic features of hemoglobins Lepore, their distribution and their clinical symptoms, the authors report on a senegalese case.

[A deep skin burn caused by the local application of a traditional oily ointment of Senegal (Carapa procera)]. / Une brûlure cutanée profonde provoquée par l'application locale d'unonguent huileux traditionnel du Senegal (Carapa procera).

Many traditional ointments are utilized in Senegal because of their local effects. We report the case of a new born girl deeply burned by the application of "Touloucouna" (Carapa Procera) on her skin. The berries of the tree contain cyclic terpens (Meliacine) well known for inducing inflammation by contact with the skin. They are most likely responsible for that burn until now, such injuries have never been described with Touloucouna.