[Prospective study of the effects of amiodarone on thyroid function in chagasic patients in an area of iodine deficiency]. / Estudo prospectivo dos efeitos da amiodarona na função tiroidiana de pacientes chagásicos em área de deficiência de iodo.

In order to evaluate the development of thyroid dysfunction during chronic amiodarone treatment in an area deficient in iodine and endemic for Chagas' disease, a group of 24 patients was prospectively studied. Clinical examination and measurement of serum T4, T3, rT3, TSH and antithyroglobulin antibodies were performed before and at 3 and 9 months of use of amiodarone. A TSH response 30 minutes after IV injection of 200 micrograms of TRH was also compared to TSH basal levels before and during amiodarone treatment. Thyroid radioactive uptake and scan were obtained before and nine months after amiodarone was started. Elevated rT3 concentrations were unexpectedly found in two thirds of the patients before treatment. Thyroid dysfunction developed during amiodarone administration in 20.8% of the patients; 12.5% became hyperthyroid and 8.3%, hypothyroid (with negative antithyroglobulin antibodies). Positive RAI uptake was seen in one patient with hyperthyroidism and diffuse goiter. Since T3 levels were not found to increase, the diagnosis of amiodarone-related hyperthyroidism was better evidenced by the reduced or blocked TSH response to TRH. Elevated TSH concentration was the best evidence of amiodarone-induced hypothyroidism. Increase in TSH levels since the beginning of amiodarone therapy may predispose to the growth of a goiter. In conclusion, amiodarone treatment in an iodine deficient area as above should be judiciously decided and thyroid function carefully monitored before and during the use of the drug.

The inactivating effect of Bothrops jararaca and Waglerophis merremii snake plasma on the coagulant activity of various snake venoms.

Plasmas of the poisonous snake Bothrops jararaca and of the non-poisonous snake Waglerophis merremii were not clotted by various snake venoms. These plasmas also inactivated venom clotting activity on human plasma. This effect was absent in snake serum and in heated snake plasma. The active fraction was isolated by gel chromatography from B. jararaca plasma and corresponded to the fibrinogen-containing fractions. It is suggested that the inactivation by snake plasma of the venom coagulant activity might be due to a fibrinogen-bound complex or to fibrinogen itself.

The mitochondrial function in hemosome formation and hemoglobin biosynthesis.

1. Rabbit-kidney epithelial cell cultures were induced to synthesize hemoglobin, by previously mixing cell suspensions with solutions containing reticulocyte free globin, hemoglobin and anemic rabbit blood plasma. As control, a solution without globin was used. 2. After a 24 hr culture growth period, hemoglobin was absent, as stated through electrophoresis, suggesting hemoglobin denaturation: mitochondria interacted with the incorporated material and particles resembling ferritin molecules were found within 48 hr. 3. Mitochondria modified remarkably giving rise to lamellated bodies which recomposed to form prohemosomes, presumably containing globin and newly synthesized heme: hemoglobin was still absent up to 72 hr. 4. After 96 hr hemosomes developed and hemoglobin, apparently constituted by reticulocyte globin, was detected.

Induction of hemosome formation and hemoglobin biosynthesis in HeLa cells.

Tissue cultures of HeLa cells in Hank's medium suspension, previously mixed with a solution containing reticulocyte polysomes and/or free globin, hemoglobin and blood plasma from bled rabbits, were homogenized, and an electrophoretic pattern of hemoglobin band was obtained from the supernatant; hemoglobin denatures under the tissue culture conditions. HeLa cells show typical hemosomes, identidical to those found in immature erythrocytes of embryos, and adult mammals with hemolytic anemias. When HeLa cell suspensions are mixed with solutions void of anemic blood plasma, or containing normal rabbit blood plasma, anomalous organelles are formed in the cells, and no hemoglobin biosynthesis occurs.