Vesical Hemorrhages in Male Aleutian Mink Caused by Hypersensitivity to Sulphadimidine

During an outbreak of Salmonella abortion in mink farms receiving food from a central feed plant, sulphamezathine (a 16 % solution of sulphadimidine sodium) was added to the food to combat the infection. After 3 days of medication, some males of the Aleutian type developed severe urinary bleedings. The serum concentration of the drug was not above the recommended value in 2 severely affected animals (1.5 and 1.7 mg/100 ml, respectively). Screening tests for the extrinsic (Thrombotest and Normotest) and intrinsic (cephalin time) coagulation mechanism, fibrinogen assay, fibrinolysis (plasma clot lysis time), and platelet count were not much different from normal. Coagulation or platelet defects did not therefore seem to be the cause of the bleedings. Some of the diseased animals died, and the only necropsy finding was a greatly distended urinary bladder filled with clotted blood. Histologically, hemorrhages and necrotic changes of varying severity were found in the vesical wall. In several cases, the arteries were the structures most evidently affected, indicating that the hemorrhages were due to vascular injury (Fig. 1). The damaged vessels were sporadically occluded by thrombi. The lesions were often most evident in subserosal arteries and in the relatively large arteries situated between the inner circular and the outer longitudinal muscular layer, whereas the submucosal structures were obscured by massive extravasations of red blood cells. Occasionally, the necrotic arteries were surrounded by incipient circumferential cellular accumulations, predominantly mononuclear cells, but some eosinophils were also present (Fig. 2). Thus, in these cases the vascular damage was similar to vascular lesions frequently accompanying viral plasmacytosis (periarteritis nodosa). The possibility exists that the animals were in an early developmental stage of plasmacytosis, but no extravesical changes suggesting plasmacytosis were discovered during the microscopic examination. Although other sulphonamides have occasionally shown toxic properties when administered to mink, this preparation has not, to the authors’knowledge, previously been recorded as injurious to this species. The following experiment was performed to elucidate the toxicity of sulphadimidine sodium to male Aleutian mink.     

Toxic and Carcinogenic Effects of Dimethylnitrosamine (Dmna) in the Blue Fox (Alopex Lagopus)

Single doses of DMNA from 8 to 15 mg/kg body weight (B.W.) were given in the feed, by stomach tube or by subcutaneous application to 37 foxes. The course and intensity of the disease was not influenced by the application route, but was directly related to the amount of DMNA given per kg body weight, and caused hemorrhagic centrolobular liver necrosis and acute vessel changes especially in the hepatic vein system. The possibility of liver regeneration after a single DMNA exposure depends on the degree of damage in the hepatic vein system. Some animals can recover from the acute disease caused by DMNA. But if the hepatic vessel changes are enough pronounced, progressive changes occur in the hepatic vein system eading to liver cirrhosis. The observation period of the foxes after a single exposure was from 13 to 380 days. LD50 should not be determined after a surviving time of 3 days but rather after 4 weeks. In our material LD50 was 10 mg DMNA/kg B.W. In an experiment over a longer period of time 18 foxes divided into 3 groups were given 2 weekly doses of DMNA in food. They were treated with daily estimated doses of 1.0, 0.2 and 0.1 mg DMNA/kg B.W., respectively. The foxes in Groups 1 and 2 developed ascites, jaundice and liver failure after intake of 45–70 mg DMNA/kg B.W. The foxes in Group 1 treated with 1 mg DMNA/kg B.W. showed centrolobular hemorrhagic liver necrosis and productive vessel changes in the hepatic vein system. The second group given 0.2 mg DMNA/kg B.W. developed hemorrhagic centrolobular necrosis which healed with fibrosis leading to cirrhosis and chronic occlusion in many of the hepatic veins. In addition noduli of chondroid lamellae and foci of hematopoietic tissue and early stages of hemagiomatous liver tumors were found in the liver. The group exposed with 0.1 mg DMNA/kg B.W./day did not develop hemorrhagic centrolobular liver necrosis, but thickening in the walls of the hepatic veins. After more than 3½ years of exposure multiple hemangiosarcomae were growing out from the changed vessel walls. In an experiment over a shorter time period with daily exposure of DMNA doses in the feed below 0.15 mg/kg B.W., all the foxes were completely healthy and only some showed beginning changes in the hepatic vein walls. Hematomae were often seen in foxes dying after a single DMNA dose. One fox treated with 0.1 mg DMNA/kg B.W. died of brain bleeding after 220 days of treatment. Chronic vessel changes were found in the heart and kidneys of the DMNA treated foxes. These results emphasize the fact that DMNA gives vessel changes of a more general nature.