Synthesis and Properties of Haptens for the Development of Radioimmunoassays for Thioridazine,Mesoridazine, and Sulforidazine

For the separate development of radioimmunoassay procedures for thioridazine and its two major active metabolites, mesoridazine and sulforidazine, three haptens, respectively, 2-methylthio-, 2-methylsulfinyl-, and 2-methylsulfonyl-substituted 10-[2-[l-(2-carboxyethyl)-2-piperidinyl]ethyl]-10H-phenothiazine, were synthesized and characterized. Thioridazine hapten was coupled to bovine serum albumin, whereas the haptens for mesoridazine and sulforidazine were coupled to porcine thyroglobulin. The number of hapten residues per mole of carrier protein was determined in each case by an ultraviolet spectrophotometric method. Polyclonal antibodies to each hapten–protein conjugate were obtained in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the appropriate tritiated analyte. A hapten for the ring sulfoxide metabolite of thioridazine was also synthesized.     

Human glomeruli release fatty acids which stimulate thromboxane synthesis in platelets

The cell-free medium of isolated human glomeruli exhibited a procoagulant activity and stimulated thromboxane (TXB2) synthesis in human platelets in a dose-dependent manner. The amount of TXB2 measured was 16-fold higher than what could have been predicted (TXB2 synthesized by the platelets under control conditions plus TXB2 present in the glomerular supernatant). The lipid extract of the glomerular supernatant and its purified fraction including the fatty acids was still able to stimulate--although at a lesser degree--TXB2 synthesis in platelets. Stimulation was abolished after treatment of this fraction by charcoal or albumin. Gas chromatography/mass spectrometry analysis demonstrated the presence in the purified glomerular fraction of several long-chain saturated or monoenoic fatty acids at a total concentration of 80 microM with the following order of abundance: stearic, palmitic, myristic and oleic acids. Addition to human platelets of these same exogenous synthetic acids resulted in a dose-dependent stimulation of TX synthesis. It was maximum with three or four fatty acids tested in combination, but still present with myristic acid used separately. Arachidonic acid was absent in the glomerular supernatant. Thus the stimulation observed could not be related to a greater availability of substrate. Fatty acids did not act on platelets through a non-specific detergent effect since addition of high doses of detergents inhibited TXB2 formation in platelets. The combination of fatty acids from glomerular origin identified in the present study represents a novel factor involved in the control of intracapillary hemostasis, but different from the procoagulant activity common to many tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circulating immune complex levels in patients with schistosomiasis and complications

Circulating immune complexes (CIC), adult schistosome antibody, and total immunoglobulin concentrations were estimated in sera from 35 chronic Schistosoma mansoni patients with different infection intensities and different pathological complications. High CIC levels were present in about one-third (10/35) of the sera. Most of the patients (9/10) with elevated CIC levels also had hepatomegaly or hepatosplenomegaly. This finding is significant in the pathogenesis of schistosomal liver fibrosis and may also apply to other liver diseases, especially cirrhosis. No correlation was found between infection intensity as judged by stool egg counts and CIC levels. A reverse relationship was observed between the level of anti-adult worm IgG and CIC levels. CIC levels were elevated within 7 and 28 days after treatment in most patients. Hypergammaglobulinaemia was detected in most sera.