Hyman J. Zimmerman

Liver morphology and function tests in obesity and during total starvation.

SummaryFive markedly obese patients were subjected to complete starvation of several weeks, for the purpose of weight reduction, for periods of 10–28 days. Studies of liver function and structure were conducted prior to, during, and after the period of starvation.Liver function, including BSP excretion, was normal in 4 of the 5 patients prior to starvation, but all 5 patients had some degree of hepatic steatosis.During starvation, distinctly impaired BSP excretion occurred. During the periods of refeeding with a low-calorie diet, this liver function improved. Fatty metamorphosis tended to decrease during starvation as did the apparent glycogen content. An increase in prominence of fibrous tissue and of hemosiderin deposits was observed after starvation.

Histopathologic analysis of suspected amiodarone hepatotoxicity

This analysis of the morphology of suspected amiodarone (AD) liver disease is based on a study of liver specimens from 17 individuals. Changes similar to alcoholic liver injury were commonly seen. Steatosis, both macrovesicular and microvesicular, was the most frequent histopathologic feature. Ballooning of hepatocytes, Mallory bodies, and fibrosis were also common. Other changes included nuclear unrest, acidophilic bodies, foam cells, glycogenated nuclei, and portal inflammation. Characteristic lamellar lysosomal inclusion bodies representing phospholipidosis were found in two of 14 specimens studied ultrastructurally. These changes of pseudoalcoholic hepatitis and/or phospholipidosis were present in liver specimens from asymptomatic, anicteric patients with mild elevations in serum aminotransferase or alkaline phosphatase values with or without hepatomegaly, as well as in patients with clinically overt symptoms of hepatotoxicity. Phospholipidosis appears to be a generalized systemic effect of cationic amphophilic compounds, such as AD. The cytotoxic pseudoalcoholic changes appear to be an independent phenomenon in susceptible patients, whom we speculate may have been unable or less able to metabolize AD through normal pathways. The true incidence of hepatic injury from AD remains to be determined from prospective evaluations of pretreatment and follow-up liver biopsies.

Toxicity of tricyclic antidepressants to isolated rat hepatocytes.

Abstract A series of tricyclic antidepressant drugs was tested for cytotoxicity as measured by enzyme leakage from isolated rat hepatocytes. The relative potency appeared to be: chlorimipramine / amitriptyline /- nortriptyline / desipramine / protriptyline /` imipramine. The presence of a chloro-substituent in position R 3 increased apparent cytotoxicity, and the dibenzylcycloheptene nucleus seems to be more toxic than the corresponding phenothiazine or imminodibenzyl moieties.

Editorial: Aspirin-induced hepatic injury

Excerpt Old drugs are like old friends. One knows their faults and potential for creating problems. The incidence and gravity of adverse effects of pharmacologic old friends can be weighed against ...

Drug-induced chronic hepatic disease.

A number of chronic hepatic lesions can result from adverse reactions to medicinal agents. Such lesions include a form of chronic active hepatitis; hepatic steatosis, phoepholipidosis and granulomatosis; several vascular lesions; two types of noncirrhotic portal hypertension; several types of cirrhosis and several neoplasms.

The correlation of serum levels of two transaminases with tissue levels in six vertebrate species

Abstract 1. 1. The content of aspartate aminotransferase (GOT) and alanine aminotransferase (GPT) in liver, myocardium, kidney, muscle and brain was measured in six species (guinea pig, rabbit, pigeon, chicken, rat and horse), selected because the serum levels of their transaminases cover a wide range. 2. 2. Content of GOT in all tissues except brain tended to be highest in those animals with the highest serum levels. The horse provided an exception, since despite very high serum levels, tissue levels were low. 3. 3. Content of GPT in the liver was highest in species with the highest serum levels and lowest in those with the lowest serum levels. 4. 4. These data suggest that the serum levels of some enzymes in different species are related to the tissue levels of the respective enzymes.

Adverse Effects of Chlorpromazine Metabolites on Isolated Hepatocytes

Summary Chlorpromazine (CPZ) and several of its metabolites were tested for in vitro cytotoxicity, as measured by the efflux of aspartate aminotransferase to the surrounding medium, toward isolated rat hepa-tocytes. Exposure of liver cells to CPZ, at a concentration of 9 × 10-5 M, led to enzyme leakage. The demethylated metabolites, mono- and didesmethyl-CPZ, were three and six times, respectively, more potent than CPZ. Hydroxylation of the tricyclic ring at the 7 or 8 position gives rise to compounds that were slightly less active than the parent compound, while oxidation of the sulfur atom resulted in inactive analogs. The presence of calcium in the medium had no apparent effect on the response of the hepatocytes to CPZ.

ENCEPHALOMYELORADICULITIS (GUILLAIN-BARRÉ SYNDROME) AS A COMPLICATION OF INFECTIOUS HEPATITIS

Excerpt Dysfunction of the central nervous system has been described as one of the more serious complications of infectious hepatitis.1, 2Ordinarily the picture resembles acute alcoholism, hyperins...

Drug-Induced Cholestasis in the Perfused Rat Liver and Its Reversal by Tauroursodeoxycholate: An Ultrastructural Study

Abstract Chlorpromazine at a concentration of 250 μM and estradiol-17β-D-glucuronide at 17.5 μM on infusion led to a sharp reduction in bile flow by the in vitro perfused rat liver. This was accompanied by fragmentation and a loss of canalicular microvilli, dilatation of canaliculi, and thickening of pericanalicular ectoplasm. Less prominent were the smooth endoplasmic reticulum dilatation, lysosomal lamination, and the appearance of amorphous bile in hepatocyte cytoplasm. The bile flow and electron microscopy appearance were restored to normal by infusion of tauroursodeoxycholate in a concentration of 5 μmol/min for the estradiol-17β-D-glucuronide-induced cholestasis and 1.5 μmol/min for the chlorpromazine-induced cholestasis. Changes in ultrastructure paralleled changes in bile flow. These observations demonstrate the feasibility of electron microscopy studies on the perfused liver, and the rapidity with which cholestatic changes appear.

In vivo effects of Escherichia coli endotoxin on sulfobromophthalein clearance in the guinea-pig.

In vivo studies indicated that the primary effects ofE. coli endotoxin on hepatic clearance of sulfobromophthalein were at the excretory level. Newborns were more sensitive to the LPS than older animals.