Pyrimethamine, a drug used in the treatment of toxoplasmosis, was much less teratogenic in golden hamsters than in Wistar rats. About 70% of rat fetuses were killed or malformed by administration of single oral doses of 5 mg to pregnant females. Less than 10% of hamster fetuses died or were malformed following single doses to the mother of 20 mg, which on a mg/kg basis was eight to nine times greater than that given to rats. In the rats repeated daily doses of 0.5 mg per female were severely teratogenic. The incidence of dead and abnormal fetuses in rats treated with 5 mg pyrimethamine was markedly reduced, from about 70 to lo%, by single intraperitoneal injections of 6 mg folinic acid; this result suggests that folinic acid might be potentially of value in lessening the teratogenic risk that may exist when pyrimethamine is employed in toxoplasmosis therapy during early pregnancy.Pyrimethamine ( 2,4-diamino-5-p-chlor-
Background: Diabetes has been shown to be an accelerating factor in the progression of atherosclerosis. The metabolic changes in diabetes contribute to modified platelet function and enhanced leukocyte-platelet aggregate formation. The attachment of activated platelets leads to the activation of leukocytes causing enhanced cytokine production and upregulation of surface adhesion molecules. Therefore, plateletleukocyte aggregates may be of great importance in the development of cardiovascular complications. Materials and Methods: Monocyte-platelet aggregates and monocyte Mac-1 expression were measured by flow cytometry to obtain differences between type 2 diabetic and healthy subjects. inflammatory mediators were evaluated to assess the presence of inflammation. Results: We found no signs of inflammation in type 2 diabetes; however, we observed enhanced aggregation level of monocytes and platelets. The expression of Mac-1 did not differ between diabetic and control subjects, but it was significantly higher on monocytes bearing platelets in both groups. Conclusions: Elevation of monocyte-platelet aggregates is an early marker of diabetes, which precedes the signs of inflammation. Enhanced Mac-1 expression can be observed on monocytes bearing platelets, independent from the presence of diabetes.
Complete and partid transposition of the great vessels, dextrocardia, and absence or stenosis of the tricuspid or mitral valves were encountered singly or in combination in rat fetuses from mothers injected with trypan blue solution subcutaneously on the 8th or 9th day of gestation. Hearts with transposition of the great vessels were usually characterized by shortness of the aorta and pulmonary trunk, cranial location of the aortic valve, displacement of the coronary arteries, and a channel or "track" extending from the cranial portion (infundibulum) of the right ventricle to the commencement of the transposed pulmonary trunk. Inadequate expansion of the atrioventricular ring about the 12th or 13th day of gestation possibly leads to deformity of the atrioventricular cushions and to absence or stenosis of the tricuspid or mitral valves. Sinuosity of the truncus arteriosus seen in many 13th day and older embryos of the trypan blue series is considered a significant factor in the development of transposition of the great vessels.
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