Joseph Cascarano

ACTIVITY OF KREBS CYCLE DEHYDROGENASE SYSTEMS IN LIVER AND SPLEEN OF RATS AFTER WHOLE-BODY X-IRRADIATION

By the use of a tetrazolium salt, INT, the dehydrogenase system activity of homogenates of liver and spleen was measured microchemically in three portions of the Krebs cycle: malate-dependent, succinate-dependent, and isocitrate- dependent. Young adult CFN male rats were used, and liver and spleen homogenates were assayed at specific periods after irradiation. Liver was found to be more sensitive than spleen to whole-body x irradiation. Both organs showed a fall in activity as early as 5 to 10 min postirradiation. (auth)

CHANGES IN THE INTRAHEPATIC CIRCULATION AND THE RETICULOENDOTHELIAL SYSTEM INDUCED BY INHIBITORS OF MONOAMINE OXIDASE

The chronic administration of monoamine oxidase inhibitors in man produces pathological manifestations that are believed to result primarily from their action on the liver. For the most part the toxic effects have been documented by routine pathology and clinical chemistry,l but to date these measurements have not been sufficiently critical to define the basic property of these drugs that is responsible for the hepatotoxic sequelae. Inasmuch as the toxic course of the syndrome had many points of resemblance to serum hepatitis, we felt that a careful study was warranted of the reticuloendothelial system (RES), which is the major defense mechanism against bacterial and viral infections. Factors that interfere with the behavior of the RES have been found, in turn, to lead to damage of the parenchymal elements of the liver. Impairment of the RES was associated with a greatly increased susceptibility of the animal to infectious processes and to various types of systemic and local injury. Study of the RES has been greatly facilitated by the recent development of methods for quantitatively measuring the phagocytic function of the RES and, by this means, for measuring liver blood flow? In essence, a colloidal suspension of carbon is injected into the blood stream and the rate of clearance of the colloid is then studied. The circulating carbon is removed from the liver proper by the phagocytic activity of the Kupffer elements. Under normal circumstances the topographical distribution of carbon within the liver lobule reflects the pattern of blood flow through the tissue, the uptake of carbon by the Kupffer cells being a function of the concentration in the blood stream and the volume of blood flowing past the R E elements. Histological inspection shows that the phagocytized material is scattered diffusely throughout the lobule, with the Kupffer cells in the periportal region showing a somewhat heavier coloration. Under abnormal circumstances, the uniform pattern is no longer present. The absence of carbon in particular areas can be attributed to one of two possible causes, namely, interference with the phagocytic mechanism per se, or to a curtailment of the circulation through these sinusoids. By measuring both the rate of clearance as an index of the phagocytic activity and the histological distribution of carbon i t is possible to obtain a broad over-all approximation of liver circulation. The rate a t which carbon is cleared from the blood stream has been used as a quantitative measure of the phagocytic function of the RES? In the case of colloidal carbon more than 80 per cent of the carbon is taken up by the liver elements and less than 10 per cent by the spleen, the other major tissue containing large numbers of phagocytic elements. The carbon-clear* The work reported in this paper was supported in part by a grant from Hoffmanii-1.a Roche Inc., Nutley, N. J. Established Investigator of the American Heart Association, New York, N. Y.

Anaerobic Cell Function: Effect of Fasting on Cation Transport in Rat Liver Slices

Summary Rat liver slices from fed or fasted animals do not have the ability to conduct cation transport when subjected to anoxia. However, anoxic cation transport can be stimulated in liver slices of fed animals when slices are preincubated under O2. In addition, anoxic cation transport can be stimulated by incubation of slices in pyruvate, oxalacetate, or phosphoenolpyruvate. These conditions did not stimulate anoxic cation transport in liver of fasted animals. All attempts at metabolite reconstitution also failed to elicit anoxic cation transport in liver of fasted animals.

Glycogen Synthesis in Rat Liver Slices Role of Glucose Concentration, Mesothelium and Insulin.

Summary The penetration of glucose into liver slices under in vitro conditions was determined histochemically by staining for glycogen. The width of the glycogen band was found to depend on glucose concentration in the medium. The extent to which glucose penetrates mesothelial surfaces was about half that observed at cut surfaces. Although insulin increased glucose penetration 2-fold along the mesothelial surface, there was no comparable effect at the cut edge.