Abstract. A nephropathy with severe tubular atrophy was observed in Beagle dogs after oral administration of K2HP04 for 14 or 38 weeks. We describe the complete lysosomal degradation of atrophying tubular epithelial cells.During two experiments of 14 and 38 weeks duration, respectively, a total of 15 Beagle dogs received 0.8 g KnHPOJkg body weight daily with their food. All dogs were examined clinically at regular intervals. Renal biopsies were taken in the fourth week from beagles of the 14-week study. Results were compared with those of control dogs. At the end of the experiments the animals were killed and necropsies done. Different stains and histochemical reactions were applied to paraffin sections of the kidneys. Acid phosphatase and P-glucuronidase were found on cryostat sections. Kidneys futed by perfusion of five Beagles from the 38-week study and three Beagles of the 14-week study, and from five control dogs, were examined electron microscopically. Ultrahistochemically, acid phosphatase was demonstrated.Clinically, the dogs in both experiments vomited, were cachectic, and had elevated creatinine and blood urea nitrogen. Morphologically, qualitatively identical changes were seen, but the renal damage was most marked at 38 weeks. There were disseminated tubular atrophy (usually of the proximal tubules), focal scar tissue and nephrocalcinosis. The following pathogenesis was established for the lesions of the proximal tubule: Tubular atrophy begins with loss of differentiation of epithelial cells. Enzyme histochemistry, ultrahistochemistry and electron microscopy show an increase in autophagic vacuoles and autophagolysosomes. The lysosomal bodies showing fusion enclose large parts of the cytoplasm as the process continues. Complete lysosomal degradation of epithelial cells and extrusion of large lysosonies into the tubular lumen follow. After complete enzymatic digestion of the intratubular detritus, the residue is empty, convoluted and collapsed tubular basement membrane. Atrophic tubular epithelial cells have many organelle-free zones at their base, which contain fine filamentous material resembling that of the basement membrane.The degradation processes described here may explain why clinically the urinary sediment contains few cylinders and epithelial cells and why proteinuria decreases significantly toward 699
1 Groups of 60 male and 60 female B6C3F1 mice or Han- Ibm Wistar rats were exposed to HFA-134a using snout- only inhalation exposure techniques for periods of one hour daily for at least 104 weeks. HFA-134a was deliv ered directly from cylinders at vapour concentrations of 2500, 15 000 and 75 000ppm for mice and from metered-dose inhalers at vapour concentrations of 2500, 10 000 and 50 000ppm for rats. 2 Intended dosages were achieved. 3 Evidence of absorption was found at each dose level and was dose related. 4 Neither species suffered any treatment related effects on survival, clinical signs, body weights, haematology nor on the type, incidence, site or severity of gross lesions. 5 There was no effect of treatment on the type, incidence, site or severity of neoplasms in mice or rats. 6 There were no non-neoplastic findings related to treat ment in mice. 7 HFA-134a was considered not to be oncogenic and to provide a safe alternative to chlorofluorocarbons for use in pharmaceutical metered-dose inhalers.
The subcutaneous injection of a rat skin extract inhibits sebum excretion. The mitotic rate in the sebaceous glands is reduced. Therefore, a chalone of the sebaceous gland seems to exist. The regulation of sebum excretion is discussed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.