chiniofon and Liver-Diseases

Linomide is an immunomodulator that ameliorates several autoimmune and inflammatory diseases. We assessed the effect of Linomide on microvascular perfusion failure, leukocyte recruitment and hepatocellular injury induced by tumor necrosis factor alpha (TNF-alpha) and D-Galactosamine (Gal).. After 3 days of Linomide pretreatment (1, 10 and 100 mg/kg/day), rats were challenged with TNF-alpha/Gal for 24 h. Microvascular perfusion, leukocyte-endothelium interactions in hepatic postsinusoidal venules and leukocyte sequestration in sinusoids were evaluated using intravital microscopy. Liver enzymes were measured spectrophotometrically.. Challenge with TNF-alpha/Gal significantly reduced sinusoidal perfusion, and increased leukocyte rolling, adhesion and liver enzymes. Interestingly, pretreatment with Linomide (10 and 100 mg/kg/day) significantly reduced TNF-alpha/Gal-induced leukocyte rolling by 65 and 63%, and leukocyte adhesion by 87 and 84%, respectively. Moreover, Linomide (10 and 100 mg/kg/day) decreased sinusoidal sequestration of leukocytes by 71 and 51%, and markedly improved sinusoidal perfusion. Moreover, Linomide reduced aspartate aminotransferase by 87-97%, and alanine aminotransferase by 79-96%. However, Linomide had no protective effect when administered concomitantly with TNF-alpha/Gal.. These data demonstrate a dose-dependent inhibitory effect of Linomide on perfusion failure, leukocyte recruitment and hepatocellular injury provoked by TNF-alpha. Indeed, these findings suggest that Linomide may be an effective substance for protection of the liver in sepsis.

Topics: Adjuvants, Immunologic; Animals; Antineoplastic Agents; Cell Adhesion; Cell Communication; Chemical and Drug Induced Liver Injury; Endothelium, Vascular; Galactosamine; Hydroxyquinolines; Leukocytes; Liver; Liver Diseases; Male; Microcirculation; Rats; Rats, Sprague-Dawley; Sepsis; Tumor Necrosis Factor-alpha

The kinetics and distribution in vivo of autologous 111-In-labelled platelets were studied in 20 patients with chronic hepatic disease. The patients, 16 of whom were thrombocytopenic, exhibited a shortened platelet mean life time, a reduced platelet recovery and a normal platelet turnover, the latter 2 of which were positively correlated to the platelet count. Platelet in vivo recovery was negatively correlated to the spleen volume. In accordance with this, scintigraphic studies revealed that the spleen was the major organ of platelet sequestration and destruction, the role of the liver being almost negligible. Signs of platelet destruction in the bone marrow were also found. Our results indicate that splenic platelet pooling and accelerated platelet destruction, accompanied by inability of the bone marrow to compensate for the thrombocytopenia are the main causes of the thrombocytopenia accompanying chronic hepatic disease.

Topics: Adult; Aged; Blood Platelets; Bone Marrow; Cell Survival; Chronic Disease; Female; Humans; Hydroxyquinolines; Indium; Kinetics; Liver; Liver Diseases; Male; Middle Aged; Organometallic Compounds; Oxyquinoline; Platelet Count; Radioisotopes; Radionuclide Imaging; Spleen; Thrombocytopenia

The complex 99mTc-Sn-8-hydroxyquinoline-7-carboxylate (99mTc-bioquin-7CA) was investigated in animals as a potential hepatobiliary scanning agent. Following intravenous injection, the complex was found to localize in the liver rapidly and in the gallbladder in 5--15 min; after 15 min it was excreted into the biliary tract with a high degree of specificity. Urinary excretion was negligible, reducing scan interference from the kidneys. Distribution studies in mice compared well withe localization of activity observed in rabbit scans. Preparation of the complex was rapid and simple; stannous ion was used as the reducing agent.

Topics: Biliary Tract Diseases; Hydroxyquinolines; Liver Diseases; Oxyquinoline; Technetium

Topics: Acute Disease; Chloroquine; Colitis, Ulcerative; Diagnosis, Differential; Dysentery, Amebic; Emetine; Feces; Female; Humans; Hydroxyquinolines; Hyperbilirubinemia; Liver Diseases; Male; Transaminases