Search

Lysozyme, or muramidase, is an enzyme contained mainly in granulocytes (neutrophils), monocytes and tissue macrophages. In order to study physiopathological blood and urinary variations, we have perfected a semi-automatic determination system by kinetic enzymatic means. We studied the qualities of this method and in particular tackled the problems of inhibitors. The terms of reference were based on a population of blood donors leading to a reference of 4 to 11 μg/ml for serum and approximately 0.1 to 1.8 μg/ml for urine.

It has been shown that patients with acute promyelocytic leukemia (AML3 subtype) treated with all-trans retinoic acid (all-trans RA), 45 mg/m2/day, achieve complete remission through differentiation of the leukemic clone to mature myeloid cells, which die spontaneously. The pharmacokinetics of all-trans RA given by mouth were studied in 15 AML3 patients. Blood samples were drawn for 24 h following a single oral dose of 45 mg/m2 and assayed for all-trans RA and 13-cis retinoic acid (13-cis RA) plasma concentrations by specific high-performance liquid chromatography. In one patient all-trans RA and 13-cis RA levels were below the detection limits at all times. In the other patients, the time to peak concentration of all-trans RA was between 60 and 210 min (median 90 min) after ingestion, with maximum concentrations between 0.03 and 2.5 micrograms/ml (median 0.4 micrograms/ml). These concentrations were within the in vitro differentiating concentration range of all-trans RA for these patients' cells. In nine patients, enterohepatic cycling was suggested by the presence on the concentration versus time curve of a secondary peak that occurred at meal times. The apparent plasma elimination half-life was between 16.8 and 77.4 min (median 30 min). Detectable plasma levels of 13-cis RA in 12 patients indicated in vivo isomerization of all-trans RA. Despite the high inter-individual variability of all-trans RA pharmacokinetics in these patients, high blast cell counts and failure to respond to differentiation treatment tended to be associated with low all-trans RA Cmax values and high clearance estimates.

Subacute transmissible spongiform encephalopathies (STSE) represent a cause of presenile dementias, found in man (Creutzfeldt-Jakob disease, Gerstmann-Straussler syndrome, Kuru), in sheep and goats (scrapie), in cattle (bovine spongiform encephalopathy) and in various mammals. It seems that the frequency of the human spongiform encephalopathy (HSE) is more frequent than thought up to now and an alimentary origin is not to be discarded. Many discussions are held concerning the nature of the transmissible agent: virus, virino, prion? Isolation of an abnormal protein, the isoform PrPSc resulting from an unknown alteration of a protein PrPc encoded in man by the chromosome 20 is presently the basis for seeking the cause of transmissible dementias. Molecular genetic studies of the gene PrP have demonstrated the existence of many mutations: are they the actual cause of the STSE or only a favouring factor? The existence of familial sporadic or infectious forms of HSE might be explained by alterations of the conformation of PrPc into PrPSc, able to induce this structure modification to last when thereafter the synthesis of the normal protein is achieved. The "chaperone" protein model can be questioned in this respect. For the moment the research work is developed into characterization of humoral or genetic markers able to detect the predisposed subjects in high-risk families. HSE are also an interesting model for other types of dementias, especially the Alzheimer disease which is still the preferred target of research in this field.

In infantile autism, the serotoninergic (5-HT) hypothesis is corroborated by biological dosages and therapeutic effects of fenfluramine which decrease blood serotonin. However other drugs, such as dopaminergic agonists or antagonists, have therapeutic effects. Therefore, we tested the hypothesis that two dopaminergic (DA) drugs have a similar 5-HT effect underlying the therapeutic efficiency. We evaluated in a randomized, double-blind and cross-over study, the effects of a DA agonist (bromocriptine) and a DA antagonist (amisulpride) on platelet 5-HT in infantile autism. The prolactinemia, reflecting the DA action, has been also measured. Nine children, aged from 4 to 13 years, according to the DSM III for infantile autism, received either drug in a random order during four weeks with an in-between placebo period of six weeks. The dosages of platelet 5-HT and serum prolactin were carried out at the beginning and at the end of every phase of treatment (active or placebo) with radioenzymology and radioimmunoassay methods respectively. The principal results on serum prolactin show neither order x treatment interaction, nor order effect but a significant treatment effect (p0.01): amisulpride increases serum prolactin whereas bromocriptine decreases according to the usual data. About platelet 5-HT, there is neither order x treatment interaction, nor treatment effect but a significant order effect (p0.01). Both drugs increase platelet 5-HT in the first phase of treatment. This order effect could be explained by a remanent effect of amisulpride after 6 wash-out weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

The transmissible spongiform encephalopathies (TSEs) or "prions diseases", provokes some controversies about their origins and possible transmission from animals to humans. Important advances were obtained recently on the genetical TSEs with the genotypic diagnosis methods based on the discovery of numerous mutations and inclusions in the PRNP gene coding for prion protein. The possible connection between the bovine spongiform encephalopathy (BSE) and the newvariant of Creutzfeldt-Jakob disease (nv-CJD) ask numerous questions in terms of public health. Lastly, the important problem of biological diagnosis of "prions diseases" presents interesting advances that must be continued and supported by the public health authorities.

Proteic (neuritic plaques, amyloid substances...) and genetic characteristics of Alzheimer's disease are reviewed. An infectious origin appears unlikely. After production of specific antibodies, the reported abnormal Tau proteins might represent peripheral markers of the disease. Changes in olfactory neurons, accessible for biopsy specimens, might give rise to new biological diagnosis of Alzheimer's disease.