Massive liver enlargement accompanied by decreased drug metabolism. Effect of anterior pituitary extract on hepatic ultrastructure, zoxazolamine paralysis, and metabolism in the rat

1977 ◽  
Vol 55 (5) ◽  
pp. 1135-1142 ◽  
Author(s):  
S. Szabo ◽  
B. D. Garg ◽  
P. Kourounakis ◽  
B. Tuchweber

The relationship between liver enlargement and drug metabolism was investigated in female rats. Hepatomegaly (e.g., 31% increase in liver weight in a 17-day experiment) was induced by injection of lyophylized anterior pituitary (LAP) extract The liver enlargement seemed to be due to an increase in the number and the size (enhanced water content and PAS-positive material) of hepatocytes. Electron microscopic examination of the liver revealed slight proliferation of the smooth endoplasmic reticulum and pronounced fragmentation and dilation of the rough endoplasmic reticulum. Zoxazolamine paralysis time was significantly prolonged (+55% and +102%) after 4 and 17 days, respectively, of treatment with LAP. Metabolism of zoxazolamine by the 9000 g supernatant fraction of the liver of rats given LAP for 17 days was reduced by 73%. Thus, the marked hepatomegaly induced by LAP was associated with a prolonged action of the drug which may result from a decrease in hepatic drug metabolism.

Author(s):  
F. G. Zaki

Addition of lithocholic acid (LCA), a naturally occurring bile acid in mammals, to a low protein diet fed to rats induced marked inflammatory reaction in the hepatic cells followed by hydropic degeneration and ductular cell proliferation. These changes were accompanied by dilatation and hyperplasia of the common bile duct and formation of “gallstones”. All these changes were reversible when LCA was withdrawn from the low protein diet except for the hardened gallstones which persisted.Electron microscopic studies revealed marked alterations in the hepatic cells. Early changes included disorganization, fragmentation of the rough endoplasmic reticulum and detachment of its ribosomes. Free ribosomes, either singly or arranged in small clusters were frequently seen in most of the hepatic cells. Vesiculation of the smooth endoplasmic reticulum was often encountered as early as one week after the administration of LCA (Fig. 1).


1972 ◽  
Vol 20 (12) ◽  
pp. 1006-1023 ◽  
Author(s):  
ALEX B. NOVIKOFF ◽  
PHYLLIS M. NOVIKOFF ◽  
CLEVELAND DAVIS ◽  
NELSON QUINTANA

A modification of the Novikoff-Goldfischer alkaline 3,3'-diaminobenzidine medium for visualizing peroxisomes is described. It makes possible light microscopic as well as electron microscopic studies of a recently described class of peroxisomes, the microperoxisomes. Potassium cyanide (5 x 10–3 M) is included in the medium to inhibit mitochondrial staining, the pH is 9.7 and there is a high concentration of H2O2 (0.05%). Two cell types have been chosen to illustrate the advantages of the new procedure for demonstrating the microperoxisomes: the absorptive cells in the human jejunum and the distal tubule cells in the guinea pig kidney. Suggestive relations of microperoxisomes and lipid are described in the human jejunum. The microperoxisomes are strategically located between smooth endoplasmic reticulum that radiates toward the organelles and contains lipid droplets and "central domains" of highly specialized endoplasmic reticulum which do not show the lipid droplets. The microperoxisomes are also present at the periphery of large lipid-like drops. In the guinea pig kidney tubule there is a striking difference between the thick limb of Henle and distal tubule. The distal tubule has a population of cells with large numbers of microperoxisomes readily visible by light microscopy; these cells are not present in the thick limb of Henle. Other differences between the two are also described.


1997 ◽  
Vol 3 (S2) ◽  
pp. 55-56
Author(s):  
H.J. Finol ◽  
D.D. Mondragón ◽  
Y.M. González ◽  
C. Paradisi ◽  
N. González ◽  
...  

Although liver function tests could be abnormal in humans taking cocaine the histopathological basis for this disorder has not been well established. Light microscopic studies have shown the existence of peripheral, centrilobular or diffuse necrosis. The only electron microscopic investigation we could find reports hepatocyte alterations including dilated rough endoplasmic reticulum, hypertrophy of smooth endoplasmic reticulum, and existence of phagolysosomes. In this work we report the liver ultrastructural pathology in chronic cocaine users.Liver biopsies were obtained in five male patients, 25-44 years old. These patients had consumed cocaine and other drugs (marihuana, alcohol, amphetamines, etc..) for 7-30 years. All of them had altered liver function tests. Tissue samples were processed with routine techniques for transmission electron microscopy and observed in a Hitachi H-500 electron microscope.Abnormalities observed included those previously reported as swollen rough and smooth endoplasmic reticulum, presence of autophagic vacuoles and lipid deposition.


1978 ◽  
Vol 56 (7) ◽  
pp. 738-745 ◽  
Author(s):  
D. J. Ecobichon ◽  
R. W. Dykeman ◽  
M. M. Hansell

The development of four functionally diverse, hepatic enzymes (p-nitroanisole O-demethylase, aniline hydroxylase, carboxylesterase, and glucuronyltransferase (with α-naphthol as the aglycone acceptor)) was studied in perinatal Hartley guinea pigs from 8 days prepartum to 28 days postpartum. A good correlation was observed between the activities measured in resuspended Ca2+-aggregated microsomes and the quantities of hepatic smooth endoplasmic reticulum visible by electron microscopic examination at the different stages of development. The study demonstrated that, postnatally, the guinea pig developed competent enzymatic systems as rapidly as did other laboratory species but that, prenatally, these same enzyme(s) systems were much further advanced than those in other species.


1968 ◽  
Vol 16 (5) ◽  
pp. 337-345 ◽  
Author(s):  
ZOLTAN POSALAKI ◽  
TIBOR BARKA

The alterations of hepatic microsomal fractions were studied in fasting rats given porphyrogenic doses of allylisopropylacetamide. A single dose of allylisopropylacetamide caused significant enlargement of the liver within 14 hr and in 24 hr the liver was about 49% heavier. Microsomal phospholipids of liver more than doubled in 48 hr after the administration of allylisopropylacetamide. This increase was accounted for principally by an increase in phospholipids of the smooth endoplasmic reticulum. Incorporation of 32P indi cated that the increase in microsomal phospholipids was caused mainly by a reduction of the rate of catabolism rather than by an augmentation of the rate of synthesis. Electron microscopic observations in agreement with the fractionation studies revealed a hypertrophy of the smooth membranes of the endoplasmic reticulum.


1968 ◽  
Vol 16 (9) ◽  
pp. 561-571 ◽  
Author(s):  
JOHN B. EMANS ◽  
ALBERT L. JONES

Progesterone given daily for several days to male golden hamsters was shown to promote an increase in liver weight and a striking increase in hepatic smooth endoplasmic reticulum. This increase in smooth reticulum observed by electron microscopy was confirmed biochemically through microsomal phospholipid measurements. The alterations in liver structure brought about by administration of progesterone are comparable to those induced by phenobarbital. Hypertrophy of the smooth reticulum is seen in the form of a delicate system of interwoven tubules which freely anastomose and often are seen in confluence with the lamellar profiles of rough reticulum. Progesterone-induced hypertrophy of the hepatic smooth endoplasmic reticulum demonstrates that this organelle is responsive to an endogenous compound normally present in the circulation, and suggests that stimulation by steroids may be responsible in part for the maintenance of microsomal hydroxylases and smooth reticulum in the normal hepatic cell.


2018 ◽  
Vol 7 (3) ◽  
pp. 113-116
Author(s):  
L. G. Nikonova ◽  
V. V. Banin ◽  
I. G. Stel'nikova

Electron microscopic examination of B cells of pancreatic islets of the pancreas in dogs with normal (n=10) and impaired glucose tolerance (n=10) was performed. Ultrastructural features of the organization of insulin cells associated with an increased requirement of the hormone in the body with the latent form of diabetes mellitus are established. In B cells, signs of functional tension due to unregulated secretion, manifested by the expansion of endoplasmic reticulum cisterns, Golgi complex hypertrophy, an increase in the number of immature secretory granules and vacuoles in the cytoplasm are revealed in B cells.


Author(s):  
P. W. Coates ◽  
C. A. Blake ◽  
D. S. Maxwell ◽  
C. H. Sawyer

In rats, physiological studies show that ovariectomy results in a reduced concentration of circulating prolactin. Conversely, ovariectomized rats given estrogen have elevated serum prolactin and increased amounts of prolactin in the anterior pituitary gland. Separate electron microscopic studies suggest modifications in fine structure of prolactin producing (LTH) cells based on relatively large cumulative amounts of estrogen given alone or with comparably high doses of progesterone to adult virgin female or ovariectomized rats. This study was undertaken to provide a correlated morphological and physiological investigation of LTH cells and prolactin levels in a model commonly used by many researchers.Six to seven weeks after bilateral ovariectomy, a group of adult female rats was primed by a subcutaneous injection of 50 ng of estradiol benzoate and 25 mg of progesterone.


1978 ◽  
Vol 148 (2) ◽  
pp. 466-477 ◽  
Author(s):  
I Kushner ◽  
G Feldmann

To determine the cell of origin of C-reactive protein (CRP) and to cast light on the mechanisms leading to the acute phase response, we used an immunoenzymatic technique to visualize this protein in livers from rabbits at intervals after intramuscular injection of turpentine. CRP was detected only in hepatocytes. 8 h after turpentine injection, CRP was demonstrated in occasional periportal hepatocytes. With time, larger numbers of positive cells were detected successively in perilobular, midlobular, and centrilobular areas. On electron microscopy, CRP was detected in rough endoplasmic reticulum (RER), smooth endoplasmic reticulum (SER), and Golgi apparatus (GA). When colchicine was administered to inhibit cellular secretion of CRP, intensity of reaction and number of CRP-containing hepatocytes were substantially greater than without colchicine, but the sequence of intralobular distribution was similar. At peak serum response 38 h after turpentine injection, CRP could be demonstrated in most hepatocytes. Electron microscopic studies showed accumulation of CRP on membranes and lumina of RER, SER, GA, and in cytoplasmic vacuoles. These findings indicate that CRP is produced by progressively increasing numbers of hepatocytes after inflammatory stimulus and suggest that a mediator, acting initially in portal zones, is responsible for recruitment of cells to CRP production.


1967 ◽  
Vol 33 (2) ◽  
pp. 419-435 ◽  
Author(s):  
Eric Holtzman ◽  
Alex B. Novikoff ◽  
Humberto Villaverde

The rat ganglion nodosum was used to study chromatolysis following axon section. After fixation by aldehyde perfusion, frozen sections were incubated for enzyme activities used as markers for cytoplasmic organelles as follows: acid phosphatase for lysosomes and GERL (a Golgi-related region of smooth endoplasmic reticulum from which lysosomes appear to develop) (31–33); inosine diphosphatase for endoplasmic reticulum and Golgi apparatus; thiamine pyrophosphatase for Golgi apparatus; acetycholinesterase for Nissl substance (endoplasmic reticulum); NADH-tetra-Nitro BT reductase for mitochondria. All but the mitochondrial enzyme were studied by electron microscopy as well as light microscopy. In chromatolytic perikarya there occur disruption of the rough endoplasmic reticulum in the center of the cell and segregation of the remainder to the cell periphery. Golgi apparatus, GERL, mitochondria and lysosomes accumulate in the central region of the cell. GERL is prominent in both normal and operated perikarya. Electron microscopic images suggest that its smooth endoplasmic reticulum produces a variety of lysosomes in several ways: (a) coated vesicles that separate from the reticulum; (b) dense bodies that arise from focal areas dilated with granular or membranous material; (c) "multivesicular bodies" in which vesicles and other material are sequestered; (d) autophagic vacuoles containing endoplasmic reticulum and ribosomes, presumably derived from the Nissl material, and mitochondria. The number of autophagic vacuoles increases following operation.


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