New indole and triazino[5,4-b]indol-4-one derivatives: synthesis and studies as inotropics and inhibitors of blood platelet aggregation.

New triazino[5,4-b]indol-4-one derivatives carrying amino groups in position 3 were synthetized and tested as inotropic agents and inhibitors of platelet aggregation. 2h, 2p, 5p, and 6g are the most active as inotropic agents. Compounds were tested as inhibitors of platelet aggregation induced by adenosine 5'-diphosphate (ADP) and arachidonic acid (AA) (guinea pig whole blood). 2k, 2p, 5o, 6d, 6m, and 6o are the most active as inhibitors of the platelet aggregation induced by AA. 6d, 6h, and 6o are most active compounds also in the aggregation induced by ADP. Radioimmunoassay studies, following AA induced aggregation, measuring thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were carried out on compounds 2b, 2d, 2f, 2g, 2h, 2i, 2k, 2m, 2o, 2p, 2r, 5i, 5j, 5k, 5r, and 5f, which inhibit platelet aggregation induced by AA. None of the compounds tested turned out to be selective inhibitors. Compounds 2h and 2p showed both inotropic and platelet aggregation inhibiting activity.     

Genotoxicity of Acqueous Elutions of Industrial Soils

The genotoxicity of industrial soils was evaluated. A single cell electrophoresis assay or comet assay, using eleocyte cells of Eisenia foetida, was performed to assess the genotoxicity of aqueous elutions. These were obtained from industrial soils containing metals. All soil samples meet the environmental quality guidelines for metal concentrations. However, elutions have produced genotoxic effects at dilutions as low as 6%. Total metal concentrations for each aqueous elution could express synergistic effects of these compounds.     

Expression of interferon-alpha subtypes in peripheral mononuclear cells from patients with chronic hepatitis C: a role for interferon-alpha5

Interferon (IFN)-α is a family of antiviral proteins encoded by different genes. The biological significance of the existence of various IFN-α subtypes is not clear. We have investigated the interferon system in chronic hepatitis C virus (HCV) infection, a disease that responds to interferon-α2 therapy in only a limited proportion of cases. We analysed the expression of interferon regulatory factor (IRF)-1, IRF-2, and IFN-α subtypes in nonstimulated and Sendai virus-stimulated peripheral blood mononuclear cells (PBMC) from HCV infected patients and healthy controls. We observed that the IRF-1 mRNA and IRF-1/IRF-2 ratios were increased in PBMC from hepatitis C patients with respect to normal subjects. Sendai virus stimulation of PBMC led to a significant increase in the levels of IRF-1, IRF-2 and IFN-α mRNAs and in the production of IFN-α protein with respect to basal values in healthy controls as well as in patients with HCV infection. In addition, we found that while natural HCV infection induced increased IFN-α5 expression in PBMC, in vitro infection of these cells with Sendai virus caused a raise in the expression of IFN-α8 in both patients and normal controls. In summary, our results indicate that virus-induced activation of the IFN system in human PBMC is associated with selective expression of individual IFN-α subtypes, IFN-α5 being the specific subtype induced in PBMC from patients with chronic HCV infection.     

New Indole and Pyridazinoindole Analogs — Synthesis and Study as Inhibitors of Phosphodiesterases and as Inhibitors of Blood Platelet Aggregation

This paper presents the synthesis of new indole, pyridazino[4,5-b]indole, and pyridazino[4,5-a]indole analogs as well as a study of their “in vitro” activity as inhibitors of different phosphodiesterases isolated from dog cardiac tissue, dog aorta, and bovine platelets; the study of their activity as inhibitors of platelet aggregation in guinea pig whole blood, with ADP and arachidonic acid (AA) as pro-aggregants, is also included. The selected compounds 8-benzyloxy-3,4-dihydro-1-(3,4,5-trimethoxy)benzylideneaminopyridazino[4,5-b]indole 14g , and 8-benzyloxy-4-[(3,5-dimethyl)pyrazolyl]pyridazino[4,5-b]indole 20 present an interesting profile as potential inodilators, with a complementary, beneficial activity as inhibitors of the aggregation, activities which could possibly be related to the inhibition of the PDE's. Among the other compounds studied, 8-benzyloxy-3,4-dihydro-1-[4-(methyl)piperazino]acetamidopyridazino[4,5-b]indol-4-one 16c and 8-benzyloxy-3,4-dihydro-1-[4-(2-methoxyphenyl)piperazino]acetamidopyridazino[4,5-b]indol-4-one 16f stood out as inhibitors of platelet aggregation, with a mechanism that could possibly be related to the AA cascade.     

Pulmonary haemorrhage and focal necrotizing glomerulonephritis in a case of systemic sclerosis

Summary We report a case of a 53-year-old woman diagnosed of systemic sclerosis. She underwent an episode of pulmonary haemorrhage, characterized by haemoptysis, sudden anaemization, and bilateral alveolar infiltration during her hospitalization, which was resolved with steroid treatment. Subsequently, she developed a focal necrotizing glomerulonephritis. After searching in the literature, we have found only three cases of systemic sclerosis associated with pulmonary haemorrhage. We discuss the etiopathogenesis of this association and stress the importance of early steroid therapy.     

Design of a PC controlled test device for the study of patient motion in X-ray radiology: first applications and results.

Simulation and study of patient motion should be undertaken for different imaging techniques since all new radiological techniques or equipment must pass through evaluation processes to verify their functional capability and assess their performance compared with other equipment. A device to study the effects of motion on X-ray image quality was designed and built. The main goal of the PC controlled device developed by our group is to allow the adaptation of different phantoms and test objects. Preliminary experiments for the evaluation of different thorax screen-film systems were carried out by simulating respiratory motion. It is concluded that moving objects should be included for the comparison of screen-film systems since predictions based only on findings in stationary test conditions could lead to false conclusions.