Evidence of lowest brain penetration of an antiemetic drug, metopimazine, compared to domperidone, metoclopramide and chlorpromazine, using an in vitro model of the blood-brain barrier.

PURPOSE: The objective of the current study was to determine the ability of some antiemetic compounds to cross the blood-brain barrier (BBB) and thereby to determine possible side effects of compounds for the central nervous system (CNS). METHODS: We compared the brain penetration of some antiemetic compounds using an in vitro BBB model consisting in brain capillary endothelial cells co-cultured with primary rat glial cells. RESULTS: This study clearly demonstrated that the metopimazine metabolite, metopimazine acid, has a very low brain penetration, lower than metopimazine and even less than the other antiemetic compounds tested in this study. CONCLUSIONS: The poor brain penetration of metopimazine acid, metopimazine biodisponible form, seems very likely related to the clinically observed difference in therapeutic and safety profile.     

Cancer et environnement: le cas de l’amiante

Asbestos has been used extensively in industrialised countries for more than a century, causing ongoing increases in mortality from mesothelioma. Despite its regulation and ban in France in 1997, and because of the 30-year cancer latency period after exposure to it, mortality from mesothelioma will continue to increase in the country for several decades, peaking between 2020 and 2030. The risk of mesothelioma from asbestos exposure is dose dependent and higher for amphiboles. For lung cancer, the risk increases linearly with cumulative exposure, regardless of the type of asbestos; this risk is similar in the presence or absence of pleural plaques. Smoking acts with asbestos to greatly increase the risk of lung cancer, but the effects of asbestos and smoking are independent. Regarding low-level exposure, an excess of mesothelioma and lung cancer has been observed in the vicinity of mines, asbestos manufacturers and natural geologic sites (para-occupational, domestic and environmental exposure); we have been unable to demonstrate safe levels of asbestos exposure.     

Synthesis of Indole-Containing 2-Thiobarbituric Acid Derivatives

The synthesis of barbituric acid derivatives containing α-phenylskatyl residues substituted at C(5) is described. The initial compound was α-phenylnorgramine, which had been previously successfully used for the alkylation of a series of CH-acids, in particular, for the synthesis of diethyl-1H-indol-3-yl(phenyl)methylmalonate. This compound has been used to obtain a series of 2-thiobarbituric acid derivatives, which are expected to possess antioxidant, membrane protector, and radioprotector properties.__________Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 1, pp. 29 – 33, January, 2005.     

A novel assay for factor XIII based on cross-linking of synthetic peptides: analysis of different substrates.

A novel assay for factor XIII is described that utilizes exclusively small synthetic peptides as substrates for the cross-linking reaction catalyzed by activated factor XIII (FXIIIa). The acyl donor substrate (selection peptide) is immobilized on a microplate via biotin while the acyl acceptor substrate (detection peptide) is labeled with the fluorochrome Oregon green to allow sensitive detection without the need for secondary enzyme systems for signal amplification. Starting with an amino acid sequence from the fibrin gamma-chain (GQQHHLGGAKQAGDV) as a prototype peptide, the influence of amino acid exchanges were investigated with respect to their impact on the FXIIIa-catalyzed reaction. It was found that FXIIIa readily accepts a broad range of substrate peptides, with a proline neighboring the essential lysine having the most detrimental effect. The assay appears to be valuable for the molecular characterization of factor XIII and may be used for a deeper investigation into the substrate requirements of this final enzyme of wound repair, and eventually also for the characterization of other transglutaminases.     

Functional results of the surgery of esophageal opening hernia]

The article presents an original method of laparoscopic anti-reflux surgery, immediate and long-term results of the treatment of 132 patients with esophageal opening hernia. It also describes the analysis of the life quality of patients with the gastroesophageal reflux disease before and after the surgery.     

Assessment of metallothionein and antibodies to metallothionein in normal and autistic children having exposure to vaccine-derived thimerosal

Allergic autoimmune reaction after exposure to heavy metals such as mercury may play a causal role in autism, a developmental disorder of the central nervous system. As metallothionein (MT) is the primary metal-detoxifying protein in the body, we conducted a study of the MT protein and antibodies to metallothionein (anti-MT) in normal and autistic children whose exposure to mercury was only from thimerosal-containing vaccines. Laboratory analysis by immunoassays revealed that the serum level of MT did not significantly differ between normal and autistic children. Furthermore, autistic children harboured normal levels of anti-MT, including antibodies to isoform MT-I (anti-MT-I) and MT-II (anti-MT-II), without any significant difference between normal and autistic children. Our findings indicate that because autistic children have a normal profile of MT and anti-MT, the mercury-induced autoimmunity to MT may not be implicated in the pathogenesis of autism.     

Peptide profiling by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry of the Lasiodora parahybana tarantula venom gland.

In order to establish a venom fingerprint and a peptide profile of the Lasiodora parahybana tarantula venom gland, we used conventional methods such as reversed phase liquid chromatography coupled to an electrospray-ionisation hybrid quadrupole time of flight mass spectrometer (LC/ESI-QqTOFMS), matrix-assisted laser desorption/ionization time-of-flight-MS (MALDI-TOFMS) and direct study of L. parahybana venom by nanospray-ionization QqTOFMS (nanoESI-QqTOFMS) and a new technology for the direct analysis of fresh tissues using MALDI-TOFMS. The analysis of the crude venom allowed the characterization of specific juvenile and adult biomarkers. In situ MALDI analysis of L. parahybana venom gland sections revealed different peptide expression levels all along the gland and non-processed peptide precursors, demonstrating the power of the method for the dynamic investigation of peptide evolution in the venom gland of spiders.