Biomedical subjects
J Saric
Publications and source records attributed to J Saric.
Decreased acute hepatotoxicity of carbon tetrachloride and bromobenzene by cholestyramine in the rat.
Numerous factors are known to increase or decrease drug-induced liver injury. The aim of this study was to test the effect of cholestyramine. Cholestyramine, and anion exchange resin binding in the gut substances taken up and metabolized by the liver such as bile salts, vitamins, endotoxins, etc., could indirectly modify drug-induced toxicity. Two groups of animals were studied: cholestyramine-fed and pair-fed controls. Five days after feeding, carbon tetrachloride or corn oil was injected intraperitoneally. Liver function and histology were normal after corn oil injection in both groups. One day after carbon tetrachloride injection liver weight/body weight ratio was lower in the cholestyramine-fed than in the pair-fed group (4.0 +/- 0.4 mean +/- SD vs. 4.4 +/- 0.3, p less than 0.05). Alanine and aspartate aminotransferases were lower (618 +/- 782 IU and 242 +/- 147 IU vs. 8245 +/- 8189 and 1966 +/- 1524 IU, p less than 0.001), as was necrosis (p less than 0.05). Steatosis and inflammatory reaction were similar in both groups. Two and four days later there were no significant differences between the two groups, because necrosis was no longer a major feature in the pair-fed group. Similar experiments were performed with bromobenzene. Here too cholestyramine prevents necrosis but to a much lesser extent. These results confirm that steatosis and necrosis are independent toxic effects of carbon tetrachloride. Cholestyramine, a widely used drug in cholestasis, could provide a potentially clinically important hepatocellular resistance to toxicity from environmental agents.
Bile collection in free moving rats.
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[Metabolism of bile salts. 2 - The cholanopathies (author's transl)].
A better understanding of the mechanisms of bile acid metabolism, coupled with advances in methodology, has shown the major part played by bile salts in the pathogenesis of several diseases, such as cholesterol cholelithiasis, secretory diarrhoea and/or steatorrhoea associated with diseases of the small intestine, etc. This in turn has helped to develop effective medical treatments for some of these conditions. Considerable progress has also been made in determining the abnormalities in bile acid metabolism found in parenchymal and cholestatic liver diseases and in rare conditions associated with inborn errors in bile acid synthesis. The clinician's approach to diagnosis and treatment has thus been thoroughly modified by improved knowledge of bile acid metabolism.
[Metabolism of bile salts. 1. Control of synthesis (author's transl)].
Bile acids, which are essential to the digestion of fat, are synthetized in the liver from cholesterol, and changes in synthesis usually parallel changes in cholesterol synthesis. Mainly located in the gallbladder and intestine, they circulate several times a day between these two organs (enterohepatic circulation). The pool of bile salts remains constant, the amount synthetized daily being equal to those lost through the faeces. Bile acid synthesis is controlled by a feed-back mechanism represented by the amount of bile salts reaching the sinusoidal membranes of liver cells.
[Ultrastructural study of the different zones of the rat liver acinus after portacaval anastomosis].
Liver atrophy is a main feature in rats with a porto caval shunt. Histological studies revealed small size hepatocytes. Ultrastructural differences between periportal and centrolobular zones were noticed, in particular, the dilatation of the nuclear envelope and of the rough endoplasmic reticulum which appeared dilated, desorganized and sometimes without ribosomes, was more pronounced in the periportal zone. Hepatocytes of this zone might be more sensitive to the decrease of O2 and/or hepatotrophic factors.
Biliary function after liver transplantation.
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[Critical study of electric activity of the small intestine in the dog].
Thanks to a cross-circulation, the authors caused to survive in the abdomen of a sacrificed dog, the whole of the small intestine, the motor activity of which was analysed by electro-enterography. This experimental preparation thus eliminates polygraphic recordings of all potential variations outside the small intestine, e.g. stomach, colon, diaphragm, muscle, myocardium. One thus obtains very pure tracings of the variations of potential originating in the small intestine, recorded from bipolar serous intestinal electrodes, they show the activity of the small intestine, consisting of a permanent basal electric rhythm on which are grafted spikes contemporary of motor phenomena. In the abdominal skin there were recorded only a cutaneous slow wave which was contemporary with the deep motor phenomena.
[Letter: Decelerating jejunoplasty and vagotomy-pyloroplasty after subtotal enterectomy and right hemicolectomy].
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[Intraperitoneal lipase and trypsin in abdominal surgical emergencies. Interpretation of their levels in puncture-lavage fluids of the peritoneum].
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[A case of chronic ischemic colitis].
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Congenital portacaval shunt in rats: liver adaptation to lack of portal vein--a light and electron microscopic study.
In five rats with congenital portacaval shunt, liver atrophy, hyperplastic foci in the periportal zone, atrophic hepatocytes in the centrolobular zone, well-preserved hepatocyte ultrastructure with abundant rough endoplasmic reticulum, packed mitochondria and numerous peroxisomes were observed as in surgical portacaval shunt. However, portal triads were abnormal in contrast to surgical shunt. In large portal triads, hepatic arteries were prominent, bile ducts numerous and portal veins were lacking. Instead, small or large capillaries were seen in the portal tracts usually at the periphery. These capillaries appeared to be in continuity with nearby sinusoids presenting the ultrastructural characteristics of capillaries. These observations suggest that absence of the portal vein is compensated by formation of neocapillaries. It is assumed that these capillaries originate from periportal sinusoids and are necessary to distribute blood to all sinusoids and form a reservoir to lower arterial pressure.
Human liver passenger cells suppress autologous and allogeneic blood lymphocytes proliferation.
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[Vascular pathology of the portal vein distal branches: a rare cause of liver transplantation and a protean clinical presentation].
We report 5 cases of liver transplantation which showed phlebosclerotic lesions of the distal portal vein on the explant confirming a diagnosis of hepatoportal sclerosis. This lesion was associated with nodular regenerative hyperplasia (2 cases), incomplete septal cirrhosis (4 cases) and tumors (2 cases, 1 adenoma and 1 hepatocellular carcinoma). Indications for transplant were chronic liver failure (1 case), encephalopathy without liver insufficiency (2 cases), an adenoma (1 case), a liver mass (1 case). Three patients out of 5 had a past history of surgical portacaval shunts to treat variceal bleeding non related to cirrhosis, one had a spontaneous portacaval shunt, and 2 had undergone a splenectomy for pancytopenia. The review of liver biopsies (4 cases out of 5) performed during surgery showed distal portal vein phlebosclerotic lesions. The diagnosis of hepatoportal sclerosis associated with complications, which is obvious retrospectively, is seldom made prior to transplantation. Portacaval shunts could play at least a partial role in the progressive deterioration of the liver.
[Chronic ischemic colitis of stenosing course. Apropos of a case].
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[Perfusion-fixation of liver needle biopsy: technic].
Technical details concerning the perfusion-fixation of liver needle biopsies are described. The biopsy (less than or equal to 0,5 cm length) migrated in a Pasteur pipette filled with heparinized Ringer solution and stopped when its diameter corresponded to the internal diameter of the pipette. The pipette was cut above the upper part of the biopsy. The biopsy was perfused with a thin needle (external diameter 0.2 mm) struck in the upper part of the biopsy under binocular microscopy control. Fixation medium, 2.5 p. 100 glutaraldehyde, was aspirated at the inferior extremity of the pipette. The aspiration speed was equal to the perfusion speed (0.15 ml/min). The biopsy was perfused for 5-8 min. This simple technique allows for detailed electron microscopic examination of sinusoids, sinusoidal and perisinusoidal cells as well as of the spaces of Disse.
[Arterial and biliary complications of hepatic transplantation].
Despite progress in standardization of reconstruction procedures, arterial and biliary complications remain an important problem in liver transplantation. These complications directly affect graft survival and patient mortality. We review a series of 165 consecutive orthoptic liver transplantations performed in 146 patients including 3 children. Biliary reconstruction included bilio-biliary termino-terminal anastomosis in 88% of the cases and bilio-digestive choledoco-jejunal anastomosis in 12%. Biliary complications occurred in 15% (25/165) with more obstruction (64%, 16/25) than leakages (64%, 7/25); 28% (7/25) of these complications were related to biliary drainage (3 obstructions and 4 leakages). There were no arterial complications in the 7 patients with non-anastomotic biliary stenosis. The rate of arterial complications was 11%; with 8 stenoses, 5 thrombosis and 5 pseudoaneurysms. Among the 18 transplantations with an arterial complication, 7 (39%) also had a biliary complication. Among the 10 patients with a complete interruption of arterial blood flow (thrombosis or surgical ligature or a ruptured pseudo-aneurysm), 5 (50%) also had a biliary complication, 1 underwent early retransplantation and 2 died early. In conclusion, the biliary tree of the graft are particularly susceptible to interrupted arterial flow. Ischaemic biliary lesions predominate in the intra-hepatic biliary ducts. Biliary drainage is important.