Comparative studies on the polyamine metabolism and DFMO treatment of MCF-7 and MDA-MB-231 breast cancer cell lines and xenografts.

In order to characterize the estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells and xenografts, their growth kinetic parameters and some biochemical characteristics concerning the receptor status and polyamine metabolism were determined and compared. The doubling times calculated from the growth curves showed higher proliferation rate of MDA-MB-231 cells, both in culture (21 hours) and in xenograft (9.7 days), in comparison to the MCF-7 cells which had values of 32 hours and 11.6 days, respectively. Growth-dependent changes observed in the intracellular putrescine, spermidine and spermine concentrations indicated a higher activity of polyamine metabolism in the MDA-MB-231 cells and xenograft as well. However, biosynthetic key-enzyme ornithine decarboxylase activity (ODC, EC 4.1.1.17) showed neither characteristic differences between the two types of breast cancer, nor consistent relationship with their proliferation rate. Metabolic alterations of the MCF-7 and MDA-MB-231 cell lines grown in vitro were also reflected in the polyamine composition of their culture medium. Independently of their receptor status, both types of breast cancer were responsive to difluoromethylornithine (DFMO) treatment. DFMO inhibited the ODC activity totally and depleted the cellular polyamine levels. MCF-7 cells in culture were more sensitive to the antitumoral effect of DFMO than the MDA-MB-231 line, while the rate of growth inhibition did not differ significantly in the xenografts. The present results provided further evidence on the different polyamine metabolism of ER-positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells in vitro and in vivo, suggesting a correlation of hormonal modulation with polyamines as a determinant group of biological response modifiers.

Acute disseminated toxoplasmosis in a captive three-toed sloth (Bradypus tridactylus).

Fatal toxoplasmosis was diagnosed in a captive three-toed sloth (Bradypus tridactylus), an arboreal species of the tropical rainforests of South and Central America. In view of its specialized lifestyle and ecosystem and its low metabolic rate, B. tridactylus would seem to warrant further investigation in respect of its susceptibility to Toxoplasma gondii.

Effect of various levels of T-2 toxin on the clinical status, performance and metabolism of growing pigs.

In two sets of experiments eight groups of seven-week-old pigs weighing about 9 kg were fed for three weeks a prestarter that contained 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 10.0 or 15.0 mg/kg of highly purified T-2 toxin. The feed of the two control groups was free from T-2 toxin. Average daily intakes of toxin by the pigs were 0.38, 0.81, 1.24, 1.43, 0.93, 0.81, 0.99 and 2.5 mg, respectively. The weight gains, the feed intakes, the extent of feed refusal, the parameters of energy and protein metabolism and the serum concentrations of calcium, inorganic phosphorus and magnesium were affected to different extents by the different doses of T-2 toxin, but the data indicated that feed consumption was reduced and the activity of aspartate aminotransferase was increased by the smallest amount of T-2 toxin tested.

Effect of various levels of T-2 toxin in the immune system of growing pigs.

Four groups of seven-week-old pigs weighing about 9 kg were fed for three weeks a prestarter that contained 0.5, 1.0, 2.0 or 3.0 mg/kg of highly purified T-2 toxin. The average daily intakes of toxin by the pigs were 0.38, 0.81, 1.24 and 1.43 mg, respectively. The experimental and control pigs were immunised with 5 ml aluminum hydroxide gel-absorbed purified horse globulin on the first and fourth days of the treatment period. Blood samples were withdrawn on days 7, 14 and 21 and used for the determination of the titre of anti-horse globulin antibody, for an in vitro lymphocyte proliferation test, using purified horse globulin, phytohaemagglutinin and concanavalin-A and for determinations of the immune complex, the cytotoxic reaction and the phagocytic activity and phagocytic index of circulating granulocytes. The samples taken on day 21 were also used to determine the erythrocyte count, the mean cell volume of the erythrocytes, the haematocrit, the blood haemoglobin concentration, the leucocyte count and the proportion of T lymphocytes. At the end of the experiment samples were taken from the thymus, spleen and mesenteric lymph nodes for histological examination. The diets that contained 2 and 3 mg T-2 toxin/kg caused a significant decrease in the red blood cell count, the mean corpuscular volume and the haemoglobin concentration. A significant decrease in the leucocyte count and the proportion of T lymphocytes was observed in all the treatment groups. There were also dose-dependent, significant decreases in antibody formation and in the blastogenic transformation of lymphocytes, and mild to moderate reactive processes were observed histologically in the lymphoid organs.

Experimental infection of calves with an adenovirus isolated from sheep and related to bovine Adenovirus type 2 I. Clinical and virological studies.

Colostrum deprived calves were experimentally infected with an adenovirus isolated from sheep and related to bovine adenovirus type 2. The calves showed respiratory symptoms and mild diarrhoea from the third day after infection. Laboratory tests revealed the development of leucopenia, lymphopenia, a drop of the pH of the urine and the appearance of pathological changes in the urine. The animals shed the virus in their nasal discharge, faeces and urine. Comparing the clinical and virological findings with the previous experimental infection of lambs it is concluded, that this type of adenovirus is similarly pathogenic for the two ruminant species.