Prevention of azoxymethane-induced colon cancer by combination of low doses of atorvastatin, aspirin, and celecoxib in F 344 rats

Preclinical and clinical studies have provided evidence that aspirin, celecoxib, (cyclooxygenase-2 inhibitor), and statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) inhibit colon carcinogenesis. Chronic use of high doses of these agents may induce side effects in ostensibly normal individuals. Combining low doses of agents may be an effective way to increase their efficacy and minimize toxicity. We assessed the efficacy of atorvastatin (lipitor), celecoxib, and aspirin, given individually at high dose levels and in combination at lower doses against azoxymethane-induced colon carcinogenesis, in male F 344 rats. One day after the last azoxymethane treatment (15 mg/kg body weight, s.c., once weekly for 2 weeks), groups of male F 344 rats were fed the AIN-76A diet or AIN-76A diet containing 150 ppm atorvastatin, 600 ppm celecoxib, and 400 ppm aspirin, 100 ppm atorvastatin + 300 ppm celecoxib, and 100 ppm atorvastatin + 200 ppm aspirin. Rats were killed 42 weeks later, and colon tumors were processed histopathologically and analyzed for cell proliferation and apoptosis immunohistochemically. Administration of these agents individually and in combination significantly suppressed the incidence and multiplicity of colon adenocarcinomas. Low doses of these agents in combination inhibited colon carcinogenesis more effectively than when they were given individually at higher doses. Inhibition of colon carcinogenesis by these agents is associated with the inhibition of cell proliferation and increase in apoptosis in colon tumors. These observations are of clinical significance because this can pave the way for the use of combinations of these agents in small doses against colon cancer.     

Autoantibodies and immunoglobulin allotypes in healthy North American Blacks of different age groups

A population of 291 healthy North American Black subjects of different ages was studied for immunoglobulin (Ig) allotypes and the prevalence of autoantibodies, to determine possible associations between Ig allotypes and age, autoantibodies and age, and Ig allotypes and autoantibodies. Indirect immunofluorescence was used to detect anti-gastric parietal cell, anti-smooth muscle, anti-thyroid microsomal, anti-nuclear, and anti-mitochondrial antibodies. The sera were typed for the Ig allotypes Gm(1, 2, 3, 5, 6, 13, 14, 17, and 21) and Km(1) with a hemagglutination-inhibition assay. A significant association between advanced age and an increased prevalence of anti-nuclear antibodies was observed in females. There was no significant association between Ig allotypes and the autoantibodies tested. The results suggest that Ig allotypes are not involved in the development of autoantibodies in healthy Blacks.     

Acetylcarbocholine and acetylsilicocholine: Directly or indirectly acting cholinergic spasmogens?

The cholinergic and anticholinergic actions of nitrogen-free isosteres of acetylcholine and benzilylcholine are described. Esters of two kinds of choline analogues, carbocholine and silicocholine, were used. The spasmogenic activity of acetylcarbocholine and acetylsilicocholine on the guinea-pig ileum was identified as an indirect cholinergic action, in contrast to the direct cholinergic action of furtrethonium and the mainly non-cholinergic action of barium ions. In addition to this indirect cholinergic action, both esters show a weak anticholinergic and a weak noncompetitive “papaverine-like” spasmolytic activity. The corresponding benzilyl esters, although without an onium group, are relatively potent anticholinergic compounds.     

SYSTEMIC ALLERGIC REACTION TO INITIAL INSULIN THERAPY IN A JUVENILE DIABETIC

ABSTRACT: Dacou-Voutetakis, C. Thomaidis, Th., Roma, E., Katpini-Mavrou, A. and Economou-Mavrou, C. (First Department of Paediatrics, Athens University, Greece). Systemic allergic reaction to initial insulin therapy in a juvenile diabetic. Enhanced blast transformation to insulin. Acta Paediatr Scand, 64: 773, 1975–A 14-year-old girl with recent onset of diabetes developed a severe systemic allergic reaction to beef-pork insulin on the third day of insulin therapy. The same reaction developed following the injection of pork insulin and monocomponent insulin. The patient was induced to tolerate pork insulin by systemic de-sensitization to this insulin over an interval of 6 days. Peripheral blood lymphocytes from the patient cultured in the presence of insulin responded by increased blast cell transformation, as compared with controls, who either had previously presented local allergic reactions to insulin or never had manifested insulin allergy.     

Dengue hemorrhagic fever patients with acute abdomen: clinical experience of 14 cases

Among 328 patients with dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), 14 (4 men and 10 women, median age 44 years) had acute abdomen. DHF/DSS was initially suspected in only 2 of these 14 patients. Presumptive diagnoses of acute cholecystitis (6 acalculus and 4 calculus cholecystitis) were made in 10 patients, non-specific peritonitis in three patients, and acute appendicitis in one patients. Cholecystectomy, percutaneous transhepatic gallbladder drainage, and appendectomy were performed in three patients. Transfused blood in the three patients who underwent invasive procedures and the 11 patients who received supportive treatment included packed red blood cells (24 versus 0 units; P = 0.048), fresh frozen plasma (84 versus 0 units; P = 0.048), and platelets (192 versus 180 units; P = 0.003). Patients who underwent invasive procedures also had prolonged time in the hospital (median = 11 versus 7 days; P = 0.015). To avoid unnecessary invasive procedure-related morbidity and mortality, this report underscores the importance of a careful differential diagnosis in patients with acute abdomen in a dengue-endemic setting.