Kidney lesions in copper-deficient rats.

Rats fed a diet deficient in copper were found, in comparison to control rats, to have lesions in the cortex, medulla and papilla of the kidney. Within the cortex, the lesions consisted of mild atrophy of the convoluted tubules, thickening of their basement membranes and fragmentation of the reticulin framework. In the medulla and papilla, selected zones of the loop of Henle were disorganized, with their epithelia appearing atrophied and their basement membranes fragmented and irregular. The epithelial cells of the collecting tubules were atrophied and vacuolated and their basement membranes thickened. Throughout the kidney, blood vessels were distented and engorged with large numbers of erythrocytes. The most likely explanation for these lesions is vascular underperfusion which could be due to a primary effect of copper deficiency on the kidney or could be secondary to the other cardiovascular lesions that are known to occur in copper deficiency.

Cystic hyperplasia of the gall bladder in breeding ewes.

Reproduction in Finnish Landrace X Polled Dorset Horn ewes was accompanied by thickening of the wall of the gall bladder. The thickening was caused by hypertrophy of the epithelium, the presence of cysts, proliferation of blood vessels, glands and fibrous tissue in the lamina propria and hypertrophy of smooth muscle. The changes appeared to be initiated during pregnancy but to persist in a modified and chronic form in post-parturient animals.

Observations on the pancreas of cattle deficient in copper.

Lesions were found in the pancreas of clinically normal cattle of low copper status. In comparison with the pancreas of cattle with normal hepatic copper reserves, the abnormalities were an increase in the dry matter content and reduction in the concentrations of protein and copper in the wet tissue. Cytochrome oxidase activity and protein-to-RNA ratio were also reduced. Histologically, there were defects in acinar basement membranes, splitting and disorganization of acini, cellular atrophy and dissociation, and stromal proliferation. The pancreatic ductular system did not show atrophy or disorganization.

Changes in enterocyte mitochondria associated with deficiency of copper in cattle.

Comparisons were made between specimens of intestinal mucosa from three young Friesian steers, killed when showing clinical signs associated with copper deficiency, and three controls that had received supplementary copper. Copper deficiency was associated with marked depletion of cytochrome oxidase in the epithelium of the duodenum, jejunum and ileum, and with partial villus atrophy in the duodenum and jejunum. Enterocytes from the duodenum, jejunum and ileum showed mitochondrial abnormalities ranging from slight swelling to marked localised dilation. Many of the mitochondria not affected by swelling had a distinctly condensed appearance. These changes are discussed in relation to the copper-responsive diarrhoea that affects a proportion of cattle suffering from copper deficiency.

Adrenocortical involution in rats during oestrus synchronisation with medroxyprogesterone.

Daily treatment of female rats with medroxyprogesterone acetate in aqueous suspension resulted in adrenocortical atrophy. The doses given were those used for oestrus synchronisation. Intramuscular injections of 2-0 mg medroxyprogesterone acetate were used to investigate the atrophic process. Adrenocortical involution was associated with extensive single cell deletion (apoptosis). It is suggested that theses changes were due to suppression of pituitary ACTH secretion. The cytological changes support the concept that single cell death plays an important role in organ remodelling. Biochemical determinations of DNA, RNA, protein and dry matter, and histological examination, did not reveal significant changes in the liver.

PIP: Clinical studies were carried out with laboratory female rats to ascertain the effects of daily dosing with MPA (medroxyprogesterone acetate). Some of the rats received .8 mg MPA in 1.4 ml acqueous suspension. The others received 2 mg MPA in intramuscular injections. The doses used were those necessary for estrus synchronisation. Body weight was increased by MPA given by gastric intubation. Liver weight, dry matter, protein, DNA, and RNA were not significantly affected by daily MPA, either by intubation or by injection. Adrenocortical atrophy occurred as a result of the MPA administration. This response was dose-dependent. Histologically, the loss of adrenal weight was due almost entirely to the involution of cortical cells. The mechanism of adrenocortical atrophy involved extensive single cell deletion, due perhaps to the suppression of pituitary ACTH secretion. No changes in the liver were observed through biochemical determinations.