Effect of cefazolin on aminotransferase activity in the rat.

Cefazolin given sc to male rats in daily doses of 0.5-2 g per kilogram of body weight significantly decreased alanine aminotranferase activity in serum, liver, kidney, heart, and brain 2-4 wk from the beginning of the treatment. Serum aspartate aminotransferase was also reduced, but serum alkaline phosphatase and tissue pyruvate decarboxylase activities remained unaltered. In female rats, daily sc administration of cefazolin at 0.1-1 g/kg also brought about a dose-related reduction of alanine and aspartate aminotransferase activities, which reached statistical significance at high dose levels. The effect of cefazolin at low concentrations was partly reversed by administration of pyridoxal in vivo. Paradoxically, at higher dose levels pyridoxal potentiated the action of cefazolin on serum aminotranferases. The low enzyme activities were elevated by subsequent addition of pyridoxal 5'-phosphate in vitro. Similar results were obtained when rats were treated with isoniazid at daily oral doses of 200 mg/kg; administration of pyridoxal completely restored alanine aminotransferase activity to the normal level within 2 wk. Cefazolin was metabolized in vivo, resulting in some metabolites that probably possessed a hydrazine group, since positive reactions were obtained with p-dimethylaminobenzaldehyde and Fast Blue B salt. The potentiation of decreased aminotransferase activity by pyridoxal indicated, however, some dissimilarity in the effect between isoniazid and cefazolin.

Spontaneous pituitary adenomas in aging rats. A light microscopic, immunocytological and fine structural study.

The structural features of 26 spontaneous pituitary tumors in aging female Long-Evans rats have been investigated by different morphologic techniques including immunoperoxidase staining and electron microscopy. By light microscopy, the tumors corresponded to chromophobic-sparsely granulated acidophilic adenomas, containing numerous pigment granules and showing congestion as well as focal hemorrhages. Positive cytoplasmic staining was obtained with Herlant's erythrosin as well as with Brookes' carmoisine methods, used to detect secretory granules of prolactin cells. Immunoperoxidase technique revealed the presence of immunoreactive prolactin in the cytoplasm of many adenoma cells. Growth hormone and TSH immuno-stainings were negative. By electron microscopy, the tumors were found to consist of prolactin cells exhibiting marked variability in subcellular morphology and differing considerably from non-tumorous resting prolactin cells. A decrease in size and number of secretory granules, proliferation of rough-surfaced endoplasmic reticulum, formation of "Nebenkerne", accumulation of free ribosomes, prominence of Golgi complex and the presence of misplaced exocytosis were characteristic features of the adenoma cells and were interpreted as indicating enhanced secretory activity. Crinophagy and transformation of secretory granules into pigment deposits were striking findings in many adenomas. Since all the adenomas seemed to derive from prolactin cells and belong to the same tumor class, it is assumed that prolactin cells in female Long-Evans rats are more susceptible to oncogenic stimuli than other hypophysial cell types.

Annulate lamellae in spontaneous prolactin cell adenomas of the rat pituitary.

Electron microscopy of 13 pituitary prolactin cell adenomas, removed at autopsy from untreated female aging Long-Evans rats, revealed the presence of annulate lamellae in 3 tumors. No annulate lamellae were detected in 10 non-tumorous pituitary glands of adult untreated rats. Direct continuity was demonstrated between annulate lamellae and rough-surfaced endoplasmic reticulum, consistent with the assumption that annulate lamellae may originate from and/or transform to endoplasmic reticulum membranes. The results indicate that annulate lamellae are not uncommonly formed in prolactin cell adenomas, i.e. in cells which have a faster growth rate than non-tumorous adenohypophysiocytes.

Spontaneous Pancreatic beta cell tumor in the rat. A light and electron microscopic study.

Fine structural study of a pancreatic neoplasm found at autopsy of a 27-month-old female Long-Evans rat showed that the tumor consisted of, and derived from beta cells of the islets of Langerhans.