ABSTRACT
No disponible
Subject(s)
Male , Aged , Humans , Glycogen Storage Disease Type I/chemically induced , Platelet Aggregation Inhibitors/adverse effects , Stroke/drug therapy , RecurrenceSubject(s)
Carcinoma, Renal Cell/complications , Glycogen Storage Disease Type I/complications , Granulocyte Colony-Stimulating Factor/therapeutic use , Kidney Neoplasms/complications , Adult , Carcinoma, Renal Cell/drug therapy , Female , Glycogen Storage Disease Type I/chemically induced , Granulocyte Colony-Stimulating Factor/adverse effects , Humans , Kidney Neoplasms/chemically inducedABSTRACT
Results of hepatocarcinogenesis studies are reviewed. The studies were made using different histochemical markers which permit revealing hyperplastic nodules in the liver. Determination of the gamma-glutamyl transpeptidase, ATPase, glucose-6-phosphatase activities and the glycogen, iron, alpha-fetoprotein contents are advisable when studying early changes in different cell populations during hepatocarcinogenesis.
Subject(s)
Liver Neoplasms/chemically induced , Precancerous Conditions/chemically induced , 2-Acetylaminofluorene , Adenosine Triphosphatases/deficiency , Animals , Diethylnitrosamine , Glycogen Storage Disease Type I/chemically induced , Glycogen Storage Disease Type I/metabolism , Histocytochemistry , Hyperplasia , Iron Deficiencies , Liver/metabolism , Liver/pathology , Liver Glycogen/metabolism , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Precancerous Conditions/metabolism , Precancerous Conditions/pathology , Rats , Time Factors , alpha-Fetoproteins/analysis , gamma-Glutamyltransferase/deficiencyABSTRACT
The in vitro metabolizing method was modified and its ability to correctly identify eight known hemolytic and nine known nonhemolytic drugs of glucose-6-phosphate (G6PD)-deficient erythrocytes was evaluated. The technique is based on inducing in vitro drug metabolism by incubation of red cells and drug with a reduced NADP-generating system in the presence of phenobarbital-induced mouse liver microsomes. Thus, this system provides a model for in vivo metabolic function. The hemolytic potential of tested drugs is indicated by the extent of loss of reduced glutathione of G6PD-deficient erythrocytes during 60-min incubations. Complete agreement between the test and literature for nonhemolytic compounds was observed. The test also correctly identified six of the eight known hemolytic drugs and failed to identify two known hemolytic drugs (acetanilide and sulfacetamide). The test was also applied to 14 drugs about which there is uncertainty regarding hemolytic potential. Of the latter, DL-alpha-methyldopa; alpha-naphthol; beta-naphthol; 2,3, dimercaptopropanol; phenacetin; and menadione were found to react positively. We conclude that this in vitro assay system will be useful in predicting which new drugs will be hemolytic in G6PD-deficient patients.
Subject(s)
Drug Evaluation, Preclinical , Glycogen Storage Disease Type I/metabolism , Hemolysin Proteins/classification , Microsomes, Liver/metabolism , Animals , Glycogen Storage Disease Type I/chemically induced , Hemolysin Proteins/metabolism , Humans , In Vitro Techniques , Male , MiceABSTRACT
INTRODUCTION: Feeding of fructose for 7 days has been morphometrically shown to induce a SER-reduction and an accumulation of glycogen in rat liver cells. This hypothetical model "glycogenosis" is investigated with histochemical methods. MATERIAL AND METHODS: Rats are given a solution of 60% fructose in water as only nutritional source. Controls are given a solution of 60% glucose in water, an isocaloric Altromin-R-standard diet and an Altromin-R-standard diet ad libitum. Reversion of fructose induced metabolic changes is investigated by a 7 days fructose diet followed by an 1-4 days Altromin-R-standard diet ad libitum. Glycogen and glycogen metabolizing enzymes are demonstrated after a 7 days diet and in the course of an 1-7 days fructose diet. RESULTS AND DISCUSSION: Feeding of fructose leads to a high glycogen content, combined with a high activity of glycogen-phosphorylase and glucose-6-phosphatase in the liver parenchyma. Glycogen-synthetase activity increases during the first 4 days and then it drops to a low level. A pathological alteration of liver cell metabolism seems to be improbable, for all fructose induced changes are reversibel after 2 days of Altromin-R-standard diet. Glucose-6-phosphatase, as a marker-enzyme of the smooth endoplasmatic reticulum, is discussed to become activated by disruption of SER membranes due to fructose.
