The Effect of Monomers and of Micellar and Vesicular Forms of Non-ionic Surfactants (Solulan C24 and Solulan 16) on Caco-2 Cell Monolayers

Measurements of transepithelial electrical resistance (TEER), the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) test and monitoring of poly(ethylene glycol) (PEG) transport have been used to study the effects of the non-ionic surfactants Solulan C24 and Solulan 16, either free in solution or as an integral part of niosome bi-layers, on intestinal epithelial cells from man (Caco-2 cell monolayers). The effects on epithelial integrity and on the transport of the hydrophilic drug metformin depend on the concentration of the surfactants. At concentrations above 1% the effect on TEER of the surfactant in niosomal form and free in solution were equivalent whereas cell viability was preserved to a higher concentration of Solulans when the Solulans were present in the niosomal form. It was concluded that the toxic effect of niosomes arises from free surfactant present in the niosome suspension.     

Human mitochondrial glycerol phosphate dehydrogenase (GPDM) isozymes

• 1 A hydrophobic/phospholipid electrophoretic system has been devised which makes possible the analysis of human mitochondrial glycerol phosphate dehydrogenase (E.C. 1.1.99.5, GPD_M.
• 2 GPD_M has a wide tissue distribution in both adult and foetal life and is active in cultured lymphoblastoid cells and fibroblasts but is absent from red cells.
• 3 The solubilization procedure does not significantly alter the kinetic properties of the enzyme (K_mα-glycerophosphate = 0.04-0.07 m , Km PMS = 0.19-0.35 mm ) but the soluble form is less thermostable.
• 4 Comparisons of physicochemical characteristics, tissue distribution and coenzyme requirement point to a separate genetic determination and low level of evolutionary relatedness between GPD_M and its cytosolic counterpart GPD_s.

     

Phenotypic characterization and analysis of allogeneic T cell responses in ZAP-70 dominant negative transgenic mice

Antigen stimulation of T cells results in a series of biochemical events including the interaction of both SH2 domains of ZAP-70 with phosphorylated ITAMS on the T cell receptor. In order to study the physiological relevance of decreasing native ZAP-70–SH2 interaction in vivo, we generated transgenic mice expressing a T cell-specific, dominant negative form of ZAP-70 consisting of only the tandem SH2 domains (ZAP-NC). Phenotypically, these animals had a comparable distribution of lymphocyte subsets in the thymus and spleen compared with the wild-type (WT) controls. However, examination of peripheral blood revealed a slow but progressive decrease in the number of lymphocytes, particularly CD4⁺ cells, with age (17% reduction by 3 months, 58% reduction by 6 months). Allogeneic responses were then evaluated in vitro as well as in vivo using a subcutaneous sponge matrix implant. Although spleen cells cultured for 4 days in vitro with alloantigen developed normal functional responses, allogeneic responses generated in vivo within a subcutaneous sponge matrix were impaired. This was characterized by a depression in cytotoxic T lymphocyte (CTL) activity, a 82% reduction in the frequency of helper T cells, and a 78% reduction in the capacity of sponge-infiltrating lymphocytes to produce IL-2 in response to secondary antigen stimulation. These results indicate that although overt lymphocyte development and in vitro function were unremarkable, expression of a truncated ZAP-70 affected the in vivo survival of peripheral lymphocytes and altered the in vivo generation of functional activity to alloantigen.     

(+)-CYANIDANOL-3 FOR ALCOHOLIC LIVER DISEASE: RESULTS OF A SIX-MONTH CLINCIAL TRIAL

A prospective randomized double-blind trial of (+)-cyanidanol-3at a dose of 2 g daily (500 mg qds) for six months versus placebohas failed to demonstrate statistically significant clinical,biochemical or histological benefit in patients with biopsy-provenalcoholic liver disease although certain trends were identified.The group receiving the active drug tended to drink more bothbefore and during the trial and had mean serum aspartate aminotransferase(AsT) and gamma-glutamyltranspeptidase (-GT) levels which werehigher on admission to the trial. After the fourth week of treatment,the mean serum levels of these enzymes remained consistentlylower in the group receiving the active drug. In order to reproduce the beneficial effects of the drug observedin the rat, it is suggested that further trials be conductedwith the dosage so far used in man (ca. 20–40 mg/kg daily)increased toward that successfully employed in animal experiments(200 mg/kg daily).     

ASSESSMENT OF COGNITIVE FUNCTION IN ALCOHOLICS BY COMPUTER: A CONTROL STUDY

Results are presented of the performance by 103 alcoholics and90 controls on six computer-administered tests of cognitivefunction. The main analysis compared performance of the twogroups when pre-existing differences in intellectual capacity,as estimated by NART. were accounted for statistically. Theperformance of the alcoholics was worse, at a statisticallysignificant level, on 18 of 23 measures. Procedurally, the testswere found to offer practical advantages over conventional procedures.