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Biomedical subjects

S Friman

Publications and source records attributed to S Friman.

At least 109 records · Page 6Linked to original sources

In vivo regulation of mucosal transport of H+ and HCO3- in the feline gall bladder.

In the gall bladder of a fasting subject, a decline in the pH of the contents occurs due to secretion of H+ from the mucosa. In this study in anaesthetized cats, the gall bladder lumen was perfused with a bicarbonate buffer bubbled with 4% CO2 in air. During basal conditions, the PCO2 always rose while the pH and [HCO3-] fell in the buffer when passing through the gall bladder lumen, indicating a continuous secretion of H+ by the mucosa. This H+ secretion was enhanced by stimulation of the respective sympathetic nerves and was blocked by intraluminal amiloride. Intravenous infusion of vasoactive intestinal peptide (VIP) raised the pH and [HCO3-] in the buffer during the passage through the gall bladder lumen, indicating a secretion of bicarbonate from the mucosa. In view of the presence of sympathetic and VIP immunoreactive nerve fibres in the gall bladder wall and VIP receptors on the luminal epithelial cells, the study demonstrates that there are functional grounds for physiological variations in the secretion of H+ and HCO3- by the gall bladder mucosa. These variations may be important for the solubility of calcium salts in the gall bladder contents.

Amiloride↗

Organ transplantation in Göteborg with particular reference to kidney transplantation.

The limiting factor in organ transplantation is the availability of organs. Continuing work to improve the public's willingness to donate organs and inspire hospital staff to collaborate in organ procurement is essential. Identification of patients who will not benefit from transplantation can also increase the availability of organs. Grafts may also be saved by identification and appropriate treatment of recurrent renal disease. Xenotransplantation may eventually solve the problem, but major obstacles remain. Meanwhile, work in this field may help to clarify mechanisms of rejection. New immunosuppressive drugs may improve graft survival and reduce the incidence and progression of chronic rejection.

ABO Blood-Group System↗

Adjuvant treatment with ursodeoxycholic acid prevents acute rejection in rats receiving heart allografts.

Adjuvant treatment with ursodeoxycholic acid (UDCA) for liver-transplant recipients has been reported to reduce the frequency of acute rejection episodes. To explore this effect further, UDCA was given to rats in an experimental heart transplantation model, with or without concomitant immunosuppressive treatment with antihymocyte globulin (ATG). UDCA was administered orally 7 days before and 14 days after transplantation. Rats treated with UDCA alone or in combination with ATG were compared with untreated controls and ATG-treated recipients. Adjuvant treatment with UDCA was found to induce prolonged graft survival and increase the amount of transplant tolerance in rats. Serum levels of bilirubin and aminotransferases were not altered irrespective of the UDCA dose given. The results indicate that UDCA has an immunomodulatory capacity that might not be restricted to the liver, but also might apply to other transplanted organs as well.

Animals↗

The bile acid independent flow is reduced in the transplanted liver.

Bile secretion is an important indicator of liver graft function. Reports on bile formation by the transplanted liver with stable function some months after operation are scarce. In this study bile flow, bile salt secretion rate (BSSR) and biliary clearance of polyethylene glycol (PEG) 900, a marker of canalicular bile flow, were studied in a group of liver-transplanted (LTX) patients (n = 8) 3-6 months after transplantation. A group of cholecystectomized patients with indwelling T-tubes (n = 6) served as a control group. Both groups were treated with oral ursodeoxycholic acid (500 mg/day). On the day of the study bile was drained for 6 h by gravity and four-hourly samples were used in the calculations. The relation between bile flow and BSSR analysed with linear regression showed a reduced bile acid independent flow in the liver-transplanted group (0.11 ml/min) compared with the control group (0.20 ml/min). The relation between biliary clearance of PEG 900 and BSSR showed a significantly steeper slope for the cholecystectomized control patients (1.40 ml/micromol) compared with the liver-transplanted patients (0.30 ml/micromol). We conclude, that in spite of stable graft function with normal liver enzmyes, the transplanted liver has a reduced bile acid independent bile flow. The transplanted liver also has a reduced biliary clearance of PEG 900 indicating a reduced canalicular bile flow. The cause of this impaired bile formation could be due to the influence of the immunosuppressive drug cyclosporin, the result of damage to the liver during preservation and reperfusion or the continuous immunological challenge to the graft.

Adult↗

Adjuvant treatment with ursodeoxycholic acid reduces acute rejection after liver transplantation.

Acute rejection, occurring with a reported frequency of 50-70%, is still a dominating problem after liver transplantation. Medication with ursodeoxycholic acid (UDCA) has beneficial effects in different cholestatic conditions and has also been shown to reduce HLA class I antigen expression on hepatocytes in patients with PBC. Since August 1989 we have consecutively treated all patients with primary graft function with UDCA (n = 41). Patients transplanted in the first half of 1989 served as a control group (n = 8). All patients in this study were given sequential quadruple drug immunosuppression. The treatment group were given oral UDCA 10 mg/kg per day. During the first postoperative month, 17% of the UDCA-treated patients had an episode of acute rejection compared with 75% of the control patients (P < 0.01). Liver biochemistry tests 1 month postoperatively were significantly better in patients treated with UDCA. The results suggest that adjuvant treatment with UDCA reduces acute liver graft rejection.

Acute Disease↗

Functional and morphological relationships between the feline main pancreatic and bile duct sphincters.

To analyze the relationships between the bile duct and main pancreatic duct sphincters, the resistance to flow through these sphincters was studied simultaneously with perfusion techniques in anesthetized cats. Basal flow resistance was higher in the pancreatic sphincter than in the bile duct sphincter. The pressure in one duct system was not affected by the flow in the other. The muscular activities in the sphincters were usually well coordinated. Distention of the upper biliary tract or the pancreatic duct system reduced the flow resistance in both sphincters. Cholecystokinin-8 (0.01 micrograms), duodenal distention, and sublingual glyceryl trinitrate (0.4 mg) also relaxed both sphincters, whereas secretin in a dose that induced pancreatic secretion had no consistent effect. Morphine increased flow resistance in both systems. These functional studies indicate that the 2 sphincters share smooth muscle fibers at the level where the flow resistances arise, and there are thus no grounds for separate control of the sphincters. There was no evidence of a functionally common sphincter ampulla. The conclusions drawn from the manometric results were supported by morphological findings in this study.

Animals↗

Biliary excretion of different sized polyethylene glycols in the cat.

Polyethylene glycol (PEG) 900 is excreted more extensively into bile than mannitol and erythritol. In this study, the biliary recovery of intravenously injected marker molecules was analysed in anaesthetised cats with ligated renal pedicles. It was demonstrated that among polyethylene glycols sized 292-1250 Da, the species sized 1074 Da was maximally excreted in the bile. After 5 h, about 12% of the injected amount of this molecular species was recovered in bile. Both larger and smaller polyethylene glycol molecules had a lower biliary excretion. The distribution of different sized PEGs in the range 766-1250 Da in serum was fairly constant and cannot explain the recovery profile in bile. 14C-Labelled mannitol was recovered in bile to the extent of 0.7% of the amount given i.v. after 5 h, a figure that corresponds to that obtained for polyethylene glycol with a size of 370 Da. Bile/plasma ratios during steady state conditions of labelled PEG 450, PEG 900, PEG 2500 and PEG 4000 were 10, 36, 3 and 4, respectively. The results may be tentatively explained by restricted passage of the larger PEG molecules into the canaliculi, and leakage of the smaller molecules from bile back to plasma.

Animals↗

Erythrocytosis after renal transplantation; treatment by removal of the native kidneys.

Erythrocytosis after renal transplantation confers risks of thromboembolic complications and therefore necessitates repeated phlebotomies and/or anticoagulation therapy. Erythropoietin production from the retained native kidneys is one aetiological possibility for this condition. During 1982-1987, 22 patients with renal transplants underwent bilateral nephrectomy because of erythrocytosis with a median duration of 13 months. The median follow-up time was 36 months. After nephrectomy, blood counts returned to normal in all patients; these remained normal in all but two patients, who relapsed with erythrocytosis after 6 and 18 months respectively. Concomitant hypertension was cured or improved in most cases. One patient had a myocardial infarction postoperatively. No other per- or postoperative complications occurred. The mean duration of hospital stay was 7.5 days. We consider bilateral nephrectomy of the native kidneys a safe and effective alternative in the management of post-transplant erythrocytosis.

Adult↗

Adrenergic influence on bile secretion--an experimental study in the cat.

The influence on bile secretion of electrical stimulation of the splanchnic nerves and arterial infusion of adrenergic agonists was studied in anaesthetized cats. The bile salt secretion was supported by a continuous intravenous infusion of sodium glycocholate. Electrical stimulation of the splanchnic nerves reduced the volume outflow of bile from 0.71 to 0.44 ml h-1 kg-1 body wt and raised the bile acid concentration in bile, while the bile salt secretion rate was not affected. This response was reduced but not blocked by pretreatment with phentolamine, an alpha-adrenergic blocker, at a dose that prevented the blood pressure response. Infusion of noradrenaline, a mainly alpha-adrenergic agonist, into the hepatic artery mimicked the response. Infusion of isoprenaline, a beta-adrenergic agonist, also reduced the volume outflow of bile from the liver. The biliary clearances of mannitol and polyethylene glycol 900, both of which are suggested to reflect canalicular events, were reduced by stimulation of the splanchnic nerves and infusion of noradrenaline. It is concluded that stimulation of the alpha-adrenergic receptors reduces the bile acid-independent bile secretion. This reduction in bile flow induced by stimulation of the splanchnic nerves and infusion of noradrenaline is elicited mainly at the canalicular level.

Adrenergic alpha-Agonists↗