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S Friman

Publications and source records attributed to S Friman.

121 records · Page 7Linked to original sources

Hepatobiliary compensation for the loss of gallbladder function after cholecystectomy. An experimental study in the cat.

The side effects of the removal of a functioning gallbladder are surprisingly few, and it has been suggested, but never demonstrated, that the hepatobiliary tract then adjusts to compensate for the loss of gallbladder function. In this study the effects of cholecystectomy on bile acid kinetics, bile flow, and biliary clearance of mannitol were studied in cats 6-8 weeks after cholecystectomy. An enhanced recycling rate of a diminished bile acid pool was found. The bile flow was reduced and the bile acid concentration in hepatic bile was increased, but fasting bile acid secretion rate was not changed. Both when the bile acid secretion rate was reduced by drainage via an acute bile fistula and when it was enhanced by intravenous infusion of glycocholic acid, there was a lower bile acid-independent flow in the cholecystectomy group. This reduced bile flow after cholecystectomy was not explained by the higher proportion of deoxycholic acid present in the bile of the cholecystectomized animals. Biliary clearance of mannitol, which is supposed to reflect the canalicular inflow, was not reduced, indicating that the reduction in bile flow is explained by a reduced fluid secretion or an enhanced fluid reabsorption in the bile ductules and ducts after cholecystectomy. In this manner the bile ducts compensate for the loss of the absorptive function of the gallbladder after cholecystectomy.

Animals↗

Enterohepatic bile-acid circulation in the pregnant cat.

Pregnancy increases the risk of gallstones. The physiological changes responsible for this are not clearly demonstrated. Adjustments in the enterohepatic circulation of bile acids have earlier been studied in pregnancy by methods involving dilution of labelled bile acids. In the present study the bile-acid circulation was measured with direct drainage methods in pregnant animals and controls. It was found that the total bile-acid-pool size was reduced to 65% in the pregnant cat (P less than 0.01) and there was a reduced accumulation of bile acids in the gallbladder after fasting 24 h (P less than 0.01). Bile-acid synthesis by the liver was not reduced and the relation between water and bile-acid secretion by the liver was unchanged. It is concluded that, in the pregnant cat, the bile-acid-pool size is reduced due to a decreased accumulation of bile acids in the gallbladder and an increased interdigestive recycling rate of the bile-acid pool (P less than 0.05). One possible explanation for the reduced accumulation of bile acids in the gallbladder is delayed emptying of the stomach, inducing a late refilling of the gallbladder after a meal.

Animals↗

Hepatic clearance of polyethylene glycol 900 and mannitol in the pig.

Fluid phase markers like erythritol and mannitol have been used to study canalicular bile secretion in the liver. It has recently been suggested that these molecules cross the ductular epithelium and thereby their biliary clearance may underestimate the canalicular bile flow. In the present study, the hepatic clearance of polyethylene glycol 900 (PEG 900), a fluid phase marker that has been used in studies of the kidney, was compared to the clearance of mannitol in the pig. We found that the hepatic clearance of PEG 900 exceeded that of mannitol by a factor of 55. After intravenous bolus injections, both mannitol and PEG 900 appeared within 1 min in bile while significant proportions of inulin were seen only after 7 min. The hepatic clearances of both mannitol and PEG 900 positively correlated to the bile acid secretion rate and were not affected by secretin infusion. The high hepatic clearance of PEG 900 compared to mannitol may be explained by a higher fluid flux into the canaliculi than previously estimated and a continuous ductular reabsorption of fluid and mannitol. Another possibility is an active transcellular vesicular transport of this molecule--an explanation that is not supported by the immediate appearance of PEG 900 in bile following an intravenous bolus injection nor by the finding that hepatic clearance of labeled PEG was not affected by a load of unlabeled marker.

Animals↗

Relationship between gallbladder histopathology and ability to concentrate biliary lipids and bilirubin. A study on gallstone patients with functioning gallbladder.

Biliary lipids and bilirubin were measured in hepatic and gallbladder bile obtained at routine cholecystectomy in 35 gallstone patients. The gallbladders had opacified at cholecystography and the cystic ducts were patent at operation. The histologic changes in the gallbladder wall were evaluated by an independent pathologist. Increasing abnormality of the gallbladder wall was shown to be associated with reduced gallbladder contents/hepatic bile ratio of biliary lipids and of bilirubin. The concentrating function of the human gallbladder thus appears to be impaired in proportion to the severity of histologic lesions in its wall. Taken together with earlier findings in vitro, this relationship suggests impaired absorption of electrolytes and water by the gallbladder mucosa, or diffusion of biliary constituents from the lumen of the inflamed gallbladder.

Bile↗

Direct measurements of enterohepatic circulation of bile acids in the cat. Influence of contraceptive steroids and oophorectomy.

Contraceptive steroids that increase the risk of gallstones reduce the bile acid pool size and increase the cholesterol saturation in bile. To analyze mechanisms behind these effects, bile acid enterohepatic circulation was studied with direct methods in cats treated with peroral contraceptive steroids for 3 months, cats oophorectomized 1-2 months before study, and female control animals. Both administration of contraceptive steroids and oophorectomy reduced the bile acid pool size and bile acid synthesis rate. Contraceptive steroids increased water secretion by the liver at low bile acid secretion rates, reduced bile acid accumulation in the gallbladder, and increased the recycling rate of the bile acid pool. Oophorectomy did not significantly change the relation between bile acid and water secretion by the liver. The reduced bile acid pool size in animals receiving contraceptive steroids can be explained by an increased recycling rate induced by an enhanced water secretion by the liver. The possibility of a direct effect on the hepatic synthesis of bile acids by both administration of contraceptive steroids and oophorectomy cannot be excluded.

Animals↗

Progeny of survivors of acute lymphocytic leukemia.

Eight successful pregnancies and one spontaneous abortion have been observed in 5 women belonging to a group of 212 Nordic children who had their antileukemic therapy discontinued before January 1, 1978. Furthermore a young leukemic man was the father of a healthy child after 4 years of intensive cytostatic therapy. No malformations have been observed in the progeny of these treated individuals.

Abortion, Spontaneous↗

Preconditioning protects against ischemia/reperfusion injury of the liver.

Ischemic preconditioning (IPC) of an organ may induce protection against the injury caused by longer duration of ischemia and subsequent reperfusion. In a standardized model of such injury in the rat liver, we used the following protocol to investigate whether adenosine played a role in IPC by preventing its enzymatic degradation by dipyridamole pretreatment according to the following protocol: group 1, nonischemic control rats; group 2, ischemic control rats subjected to 60 minutes of ischemia by clamping of the common hepatic artery followed by 60 minutes of reperfusion; group 3, IPC with 10 minutes of ischemia followed by 15 minutes of reperfusion, prior to the ischemia/reperfusion period as in group 2; group 4, pharmacologic preconditioning with administration of dipyridamole prior to the ischemia/reperfusion period as in group 2. Peripheral liver blood flow was significantly reduced during clamping (groups 2 to 4). After unclamping, blood flow was still reduced in the ischemic rats (group 2) but had returned to preclamp values in the animals that had been subjected to ischemic (group 3) or pharmacologic (group 4) preconditioning. Liver cell injury was significantly increased in the ischemia group (group 2) only. In our experimental model of ischemia/reperfusion injury in the rat liver, we found an equally beneficial effect with ischemic and pharmacologic preconditioning. Adenosine appears to be a crucial factor in IPC.

Adenosine↗

Role of cyclooxygenase-2 for fluid secretion by the inflamed gallbladder mucosa.

Inflammatory fluid secretion by the gallbladder mucosa in experimental cholecystitis is induced by activation of cyclooxygenase, which leads to an increase in prostaglandin formation. Cyclooxygenase exists as a constitutive (cyclooxygenase-l) and an inducible (cyclooxygenase-2) isoform. The aim of this study was to demonstrate the role of cyclooxygenase-2 in inflammatory fluid secretion of the feline gallbladder. Experiments were performed 10 weeks after a surgical procedure in which chronic cholecystitis was induced in cats by ligation of the cystic duct and implantation of a gallstone in the gallbladder. Gallbladder fluid transport was continuously monitored via a perfusion system. In inflammed gallbladders the continuous fluid secretion was reversed to absorption by intravenous injection of the selective cyclooxygenase-2 blocker, NS 398 (P <0.001). Increased levels of the inducible cyclooxygenase-2 were shown by immunoblotting in inflamed gallbladders. Selective pharmacologic blockage of cyclooxygenase-2 reduced the prostaglandin E2 release to the inflamed gallbladder lumen (P <0.01). These data suggest that cyclooxygenase-2 is involved in the inflammatory response during chronic cholecystitis. Selective cyclooxygenase-2 blockers may offer an alternative to traditional nonsterodial anti-inflammatory drugs with fewer side effects in patients with cholecystitis who are awaiting operation.

Animals↗