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Biomedical subjects

S Bengmark

Publications and source records attributed to S Bengmark.

At least 91 records · Page 5Linked to original sources

Pharmacokinetics of mitomycin C following hepatic arterial chemoembolization with gelfoam.

Twelve mongrel dogs were randomly allocated into two groups using matched paired-design. Catheters were inserted into the hepatic artery, hepatic vein and the femoral vein, respectively. In the first group, gelfoam supplemented with mitomycin C (MMC) was injected into the hepatic artery, whereas the second group received a hepatic arterial injection of MMC solution alone. Simultaneous blood sampling from the hepatic and femoral vein at regular intervals was performed. MMC concentrations in plasma was determined using high performance liquid chromatography (HPLC) and the pharmacokinetics of MMC were determined. MMC concentrations in hepatic and femoral veins did not differ and no significant difference in pharmacokinetics was found when comparing MMC administration into the hepatic artery with or without gelfoam supplementation. Thus, our results revealed that gelfoam could not delay the clearance of MMC from the liver.

Animals

Acetic acid-induced colitis in the rat: a reproducible experimental model for acute ulcerative colitis.

There exists no ideal model for experimental ulcerative colitis in common laboratory animals. Therefore, we tried in the present study to establish a reproducible model for inducing colitis in rats by using acetic acid. A blind loop of the colon including the cecum, ascending colon and part of the transverse colon, was brought out through two colostomies. After mechanical washing with warm normal saline, acetic acid was instilled at different doses (4, 6 and 8%) for different exposure times (10, 15, 20, 25 and 30 s). The excluded colon was examined by light microscopy on the 1st, 2nd, 3rd, 4th, 7th and 14th days after operation and acetic acid instillation. We found that 4% acetic acid for 15 s produced a moderate, superficial colitis on the 1st day after operation, whereafter a uniform colitis evolved in all rats on the 4th day after operation. The developed colitis showed morphological similarities with human ulcerative colitis. Signs of healing and regeneration of the mucosa were seen on the 7th day, and the mucosa became almost normal at the 14th day after operation. 6 or 8% acetic acid solution or exposure times exceeding 15 s resulted in severe, deep colitis with a concomitant high mortality rate. In contrast, at exposure times less than 15 s, acetic acid induced only mild superficial colitis. We conclude that by using 4% acetic acid for 15 s in the excluded colon a uniform and reproducible colitis pathologically resembling human ulcerative colitis could be achieved. Furthermore, no mortality was encountered and the general health of the rats was similar to that of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates

Effects of phosphatidylcholine and phosphatidylinositol on acetic-acid-induced colitis in the rat.

The therapeutic effects of exogenous phosphatidylcholine and phosphatidylinositol on acetic acid-induced colitis in rats were evaluated. A uniform colitis developed 4 days after instillation of 4% acetic acid for 15 s in an excluded colonic segment, also resulting in a 6-fold increase in mucosal permeability. Instillation of 12.5 mg phosphatidylcholine once daily from the day after acetic acid instillation and for the following 2 days prevented partially the development of colitis causing partial mucosal restoration. By increasing the phosphatidylcholine dose to 25 and 50 mg, a better preventive effect was achieved. By starting the phosphatidylcholine instillation immediately after the acetic acid exposure, almost complete prevention of the colitis could be obtained. Similarly, 50 mg phosphatidylinositol in each instillation with the first administration immediately after acetic acid administration resulted in complete prevention of the colitis and a significant decrease in mucosal permeability expressed as a plasma exudation into the colonic lumen. Similar results were obtained when phosphatidylcholine was administered immediately after acetic acid, but the drug then had to be applied twice daily. In contrast, a single application of the same total dose (150 mg) of the two different phospholipids, either 30 min before or immediately after acetic acid administration, could not prevent the development of colitis. It is concluded that both phosphatidylcholine and phosphatidylinositol have a therapeutic effect on the development of acetic acid-induced colitis in the rat.

Acetates

The influence of biliary obstruction and sepsis on reticuloendothelial function in rats.

Obstructive jaundice is frequently associated with septic complications and renal impairment. The present study was performed in order to evaluate reticuloendothelial system (RES) function in obstructive jaundice and the influence of a septic challenge. Male Sprague-Dawley rats were allocated into four groups (laparotomy alone, caecal ligation and puncture (CLP), ligation of the common bile duct (CBD) alone and CBD+CLP, respectively). Mortality, blood clearance and organ distribution of 125I labelled Escherichia coli were determined. Mortality in sepsis (CLP) significantly increased in jaundiced animals (p less than 0.033). Blood clearance of radiolabelled E. coli was significantly impaired in both jaundiced groups. In jaundiced animals, hepatic localisation and renal uptake of E. coli significantly increased (p less than 0.001), while radioactive counts in bile significantly decreased (p less than 0.01). Changes in organ distribution of bacteria did not depend on alterations in blood flow. Thus, RES function was impaired in jaundiced animals and mortality increased in a concomitant septic challenge in jaundiced animals.

Animals

Effect of biliary infection on common bile duct healing in the rat.

It has been postulated that biliary infection plays a role in bile duct stricture formation. The aim of this study was to verify this hypothesis and to evaluate the effect of biliary infection on common bile duct healing. A 3-mm longitudinal choledochotomy was performed in 120 rats and closed with a continuous 11/0 Ethilon suture. Common bile duct division with end-to-end anastomosis using interrupted 11/0 Ethilon sutures was performed in another 30 rats. Biliary infection was achieved in half of the animals with retrograde injection of living 046:K1:H31 strain Escherichia coli recovered from the rat colonic content. All rats with choledochotomy, including those with biliary infection, showed no bile leakage at the suture line, and the bursting pressure at the site of choledochotomy exceeded 40 mmHg as early as 24 h. Rats with common bile duct anastomosis alone showed no stricture formation for up to 6 months after operation. All rats with biliary sepsis developed complete occlusion at the anastomosis. On scanning electron microscopy, the biliary epithelium was well preserved in all rats. The study suggests that in rats with biliary sepsis the risk of bile leakage after primary closure of the common bile duct is negligible, but biliary infection may play a critical role in common bile duct stricture formation.

Anastomosis, Surgical

The effect of pancreatic islets on transplanted hepatocytes in the treatment of acute liver failure in rats.

We previously reported that co-transplantation of hepatocytes and islets of Langerhans in the spleen reduces the mortality rate after 90% hepatectomy in the rat. In the present study, we examined whether implantation of isolated hepatocytes into the pancreas is as efficient as co-transplantation of hepatocytes and islets in this respect. We found that cotransplantation of hepatocytes and islets into the renal subcapsule reduced the long-term (30-day) mortality rate after 90% hepatectomy from 100% to 36% (P less than 0.05) when performed the day before the hepatectomy. In contrast, there was no significant reduction of mortality when the hepatocytes were transplanted into the pancreas. The results show that a close proximity of transplanted pancreatic islets to the hepatocytes is of critical importance for the improved survival in acute liver failure.

Animals

Surgical treatment of pancreatic cancer. The Swedish experience.

The development at a university hospital of radical surgery for exocrine pancreatic cancer has been studied for the time period 1958-1989. It was found that the number of operations per year increased gradually, being 6.6/year during the last 5 years, giving a resection rate of 15%. The resection rate did not change during the studied time period. The size, grade of differentiation, or stage of tumor did not change. There was no significant tendency toward decreasing operation time and blood loss, although a technically more complicated operation has been done in the last 30 cases (change from total to subtotal duodenopancreatectomy). The hospital mortality rate decreased from 33 to 3%. The rate and severity of post-operative complications also strongly decreased. For the last 30 cases, there was also a prolonged long-term survival. We conclude that the total management of patients radically operated on for exocrine pancreatic cancer is today much better than it was a decade or two ago.

Diabetes Mellitus, Type 1

The functional effects of suppression of hypothermia-induced cell swelling in liver preservation by cold storage.

It is known that cellular edema and functional impairment develop during anaerobic cold storage of organs. The extent of both is related to the storage time and the composition of the preservation solution used. We studied hypothermia-induced cell swelling and its effect on liver function after cold storage preservation with either Eurocollins (EC), a number of modified EC solutions in which glucose was replaced by various concentrations of raffinose, or UW solution. After 24 h storage, tissue swelling as determined by total tissue water (TTW) in rat liver tissue slices was most pronounced in slices incubated in Eurocollins, whereas the TTW was only moderately increased in slices stored in modified Eurocollins containing 90 to 120 mM raffinose. In contrast, slices incubated in UW solution had a TTW equal to normal rat liver tissue. Furthermore, intact rabbit livers preserved with Eurocollins had an increase in the whole organ weight, while there was no weight change after preservation with the modified solution containing 120 mM raffinose (M120). In contrast, a pronounced weight loss was observed after preservation with UW solution. After cold storage, the livers were reperfused for 2 h at 38 degrees C in an isolated perfusion circuit (IPL) with an acellular perfusate. Bile flow was significantly greater in livers preserved in M120 than in those preserved with the conventional Eurocollins. However, the bile flow in the livers stored in M120 was inferior to that in the livers preserved with UW solution, which in turn was equal to that in control livers. The release of alanine-aspartate-aminotransferase into the perfusate was higher in livers preserved with Eurocollins, with or without modification, than in the livers preserved with UW solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase

Liver cirrhosis in rats: regeneration and assessment of the role of phenobarbital.

A common model for producing experimental liver cirrhosis is the administration of CCl4 to phenobarbital (PhB)-stimulated rats. However, concern may arise due to the complex actions of PhB upon liver metabolism. This study examined the role of PhB in the production of CCl4-induced liver cirrhosis in the rat. In addition, regenerative capacity of the liver after partial hepatectomy (PH) or portal branch ligation (PBL) was studied in cirrhotic rats, rats treated with CCl4 alone, and in PhB-treated controls. In rats given PhB throughout the CCl4-induction period, ascitic form of micronodular cirrhosis was found in 93% with only 3% mortality. In contrast, rats pretreated with PhB for only 2 weeks followed by CCl4 alone for 18 weeks did not develop liver cirrhosis. In most of the cirrhotic rats, PH induced hepatic regeneration associated with improved liver histology. PBL was less effective. Treatment with PhB alone for 10 weeks resulted in liver atrophy and reduced hepatic regenerative capacity. Impaired regeneration response was also found in rats treated with CCl4 alone. In conclusion, treatment with PhB throughout the CCl4-induction period seems necessary for the production of liver cirrhosis in rats. However, prolonged treatment with PhB alone results in liver atrophy and an impaired regenerative response. Therefore, though necessary for the cirrhotic model, PhB by itself has negative hepatotrophic influences which questions the thoroughness of the PhB/CCl4 experimental model.

Animals

Phosphatidylcholine prevents postoperative peritoneal adhesions: an experimental study in the rat.

Phosphatidylcholine (PC) is the main constituent of the surface-active material coating peritoneal mesothelium. It may prevent postoperative adhesion formation through production of a lubricant film on mesothelial defects. We therefore examined the effect of its soluble form on surgically induced intraabdominal adhesions in rats. The adhesions were induced at laparotomy by any of four different operative models. PC was administered intraperitoneally (20 mg/rat) or intravenously (20 mg/rat or 50 mg/rat) at the end of the operation and on the second and third postoperative day. It was found that the degree of postoperative adhesion formation was significantly reduced by the intraperitoneal injection of PC in all 4 models. In contrast, no effect was achieved by the intravenous injection of PC, not even at a very high dose level. Our results suggest that soluble PC administered intraperitoneally might be a potent adjunct in postoperative adhesion prevention.

Abdomen

Intermittent hepatic arterial or portal occlusion reduces liver tumor growth.

The effect of repeated, intermittent hepatic vascular occlusion on liver tumor growth was studied in 32 rats. An adenocarcinoma was inoculated in the left liver lobe. After 8 days, the tumor size was measured and then, in three groups, the hepatic artery was occluded intermittently during 5 days for 15 min, 1 hr, or 2 hr daily, respectively. The tumor growth after 6 days in these groups was compared with that in a group where instead the portal vein was occluded intermittently during 5 days for 15 min, and with that in a group of sham-operated control rats. In the control rats, the tumor volume (mean +/- SEM) increased from 0.16 +/- 0.03 to 1.34 +/- 0.15 cm3 during the 6 days of experiment. It was found that repeated, intermittent occlusion of the hepatic artery or the portal vein, retarded the liver tumor growth to 30-60% of the growth rate in sham-operated controls (P less than or equal to 0.015). The 15-min daily hepatic artery or portal vein occlusion was found to reduce the tumor growth rate as much as daily hepatic artery occlusion for 2 hr. It is suggested that short, daily, intermittent hepatic vascular occlusions might be efficient in the palliative treatment of liver malignancy.

Adenocarcinoma

Metabolic responses to intermittent hepatic dearterialization in the rat.

Hepatic dearterialization is a palliative treatment for irresectable liver tumours. In the current study, the metabolic consequences of hepatic dearterialization were examined in the rat. Liver glycogen content was reduced to an average of 84% following 60 min dearterialization and was further reduced to an average of 16% following 60 min reperfusion. Plasma concentration of beta-hydroxybutyric acid was elevated by an average of 65% following 60 min hepatic dearterialization. In contrast, hepatic dearterialization did not alter cholesterol and triglyceride plasma levels. In addition, the hepatic activity of hepatic lipase was reduced by 29% after 60 min of hepatic dearterialization, a reduction which remained after 60 min of reperfusion. Clearance of intravenously administered antipyrine, which reflects the activity of liver microsomal enzymes, was reduced by 37% after 60 min of hepatic dearterialization. In conclusion hepatic dearterialization is accompanied by marked activity in the processes related to carbohydrate, lipid and xenobiotic metabolism. These effects should be taken into account when treating patients with hepatic dearterialization.

3-Hydroxybutyric Acid

Insulin secretion in streptozotocin-diabetic rats transplanted with immunoisolated islets.

Islet transplantation may be optimized by islet immunoisolation to prevent direct contact between the islet graft and the host tissue. In this study, we examined the glycemia and insulin secretion in streptozotocin-diabetic rats transplanted with islets subjected to immunoisolation with Algire diffusion chamber or with microencapsulation. Two days after diabetes induction by streptozotocin (70 mg/kg i.v.), rats were transplanted i.p. with either 1500 or 3000 islets encapsulated in Algire diffusion chambers, or with either 1500 or 3000 microencapsulated islets. Controls were diabetic rats transplanted i.p. with 1500 overnight-cultured islets not subjected to immunoisolation. In these controls, normoglycemia was evident for 3 weeks and a normal plasma insulin response to glucose infusion (10 mg/min) was seen at day 10 after transplantation. It was found that rats transplanted with 1500 microencapsulated islets similarly were normoglycemic for 3 weeks and that the plasma insulin response to glucose infusion at day 10 was normal. Furthermore, rats transplanted with 3000 microencapsulated islets remained normoglycemic for 6 months, and a glucose infusion performed at 6 months in these rats showed a normal acute plasma insulin response, whereas the second phase of insulin secretion was reduced. In contrast, rats transplanted with 1500 islets immunoisolated in Algire chamber remained hyperglycemic, and rats transplanted with 3000 islets within Algire chamber were normoglycemic for only 2 weeks. We conclude that microencapsulation is superior to the use of diffusion chamber as the immunoisolation technique for islets used for transplantation.

Alginates

The function of a colloid in liver cold-storage preservation.

The value of colloid in preservation of the liver by cold storage has not yet been fully clarified. Therefore, we studied the effects of colloid on cell swelling, liver weight, and bile production after cold storage in rat liver tissue slices and isolated rabbit liver. In rat liver tissue slices cold-stored for 24 hr in UW solution, total tissue water (TTW) was the same as in the control freshly unpreserved tissue and omitting the colloid (hydroxyethyl starch) from the UW solution did not affect the TTW. However, after cold storage for 24 hr in Perfadex, TTW was markedly increased (by 100%, P less than 0.001). Omitting the colloid in this solution, dextran, or replacing it with hydroxyethyl starch, did not affect this increase in TTW. Thus, the hypothermia-induced cell swelling evident after preservation in Perfadex was not prevented by colloid. Rabbit liver cold-stored in UW solution for 24 hr lost 15.4 +/- 4.7% of weight, but omitting the colloid from UW solution decreased this weight loss to 3.1 +/- 3% (P less than 0.01). In contrast, rabbit livers cold-preserved in colloid-free Perfadex gained 23.3 +/- 5.7% in weight. Adding colloid, either dextran or hydroxyethyl starch, decreased significantly this weight gain, to 9 +/- 3.7% and 10.4 +/- 1.8%, respectively (P less than 0.01), probably as a result of colloid osmotic pressure, preventing the interstitial edema. Rabbit livers preserved for 24 hr in UW solution, with or without colloid, produced the same amount of bile as control unpreserved livers. In contrast, livers preserved in colloid-free Perfadex for 24 hr had a markedly impaired bile production (3.9 +/- 0.9 ml/100 g) as compared with control livers (15.5 +/- 2.6 ml/100 g, P less than 0.01). Colloid partially restored this impaired bile production, to 8 +/- 1.4 mg/100 g by dextran and to 8.5 +/- 1.7 ml/100 g by hydroxyethyl starch, respectively (P less than 0.01). Thus, although colloids do not prevent the hypothermia-induced cell swelling, they prevent the development of interstitial edema, and, hence, improve the liver function.

Adenosine

Improvement of the effects of intrasplenic transplantation of hepatocytes after 90% hepatectomy in the rat by cotransplantation with pancreatic islets.

Acute liver failure is associated with high mortality. Whether support with transplanted hepatocytes improves the outcome is not established. We studied the potential beneficial effects of intrasplenic transplantation of hepatocytes in conjunction with islets of Langerhans on 90% hepatectomy-induced acute liver failure in rats. We found that all control rats died within 48 hr following 90% hepatectomy. In contrast, the mortality decreased significantly in rats transplanted with 10(7) hepatocytes into the spleen parenchyma at 1-3 days prior to 90% subtotal hepatectomy, whereas no significant reduction in mortality was seen in rats transplanted with hepatocytes immediately after the operation. However, cotransplantation of hepatocytes and 400 isolated pancreatic islets into the spleen reduced mortality when performed immediately after the 90% hepatectomy. Therefore, hepatocyte transplantation reduces mortality after 90% hepatectomy only if performed prior to the hepatectomy. However, transplantation of hepatocytes in conjunction with pancreatic islets reduces mortality when performed at the same time as 90% hepatectomy. Hence, the combined transplantation of hepatocytes and islets might offer support after liver failure.

Alkaline Phosphatase

Islet allotransplantation to streptozotocin-diabetic rats. Effects of multistrain donation and ultraviolet light irradiation.

It has previously been suggested that rejection after islet transplantation in mice is prevented by using a small amount of islet tissue from several donor animals of different strains. Furthermore, it has been suggested that ultraviolet light (UV) irradiation of islet grafts prevents rejection. We therefore studied whether islet allotransplantation in the rat could be improved by using islets from donor rats of several different strains or by using UV-irradiated islets. We found that Sprague-Dawley rats transplanted with 1,000 Wistar rat islets 2 days after streptozotocin (70 mg/kg, i.v.) remained normoglycemic for only 8 +/- 1 days. The same poor result was obtained when the diabetic rats were transplanted with islets collected from donor rats of four different strains, also when only 100 islets from each donor rat were used in combination with short-term insulin treatment. In contrast, streptozotocin-diabetic Sprague-Dawley rats isotransplanted with either 1,000 islets or with 400 islets combined with a short-term insulin treatment remained normoglycemic for more than 3 months. Furthermore, rats allotransplanted with 400 UV-irradiated islets and also treated with ciclosporin remained normoglycemic for 30 +/- 3 days, whereas those transplanted either with 400 UV-irradiated islets without ciclosporin treatment or with 400 nonirradiated islets with ciclosporin treatment did not reach normoglycemia. We conclude that, in rats, multistrain islet donation is not efficient and that UV irradiation of islets does not result in long-term benefits.

Animals

Improved liver preservation for transplantation due to calcium channel blockade.

Intracellular calcium is an important determinant for cell death in organ hypothermic preservation for transplantation. In this study, we show that prevention of calcium entry improves the result of liver cold storage in UW solution. The isolated perfused rabbit liver was used. After 48 hr of cold storage in UW solution, bile production was reduced by 70% (P less than 0.005). However, by adding the calcium channel blockers verapamil or nifedipine (40 microM) to the UW solution, this reduction was abolished, and the livers produced the same amount of bile as unpreserved livers. Furthermore, addition of the calcium channel activator, BAY K8644 (40 microM), to the UW solution, reduced bile production by 50% (P less than 0.01) already after preservation for 24 hr. We conclude that calcium entry is of importance for liver function after preservation and cold storage, and that including a calcium channel blocker to the preservation solution makes long-term liver preservation safer.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Repeated dearterialization of hepatic tumors with an implantable occluder.

A new implantable device for repeated hepatic dearterialization was evaluated in 13 patients with tumors of the liver. Eleven patients had colorectal secondaries and also received cyclic intraperitoneal infusion of 5-fluorouracil. Two patients had primary hepatocellular cancer (HCC). Four patients had a variant arterial supply. The hepatic artery was occluded repeatedly for 1 hour twice daily for 1 to 17 months (mean, 8.5 months). A complete transient occlusion was obtained in all but three patients, in whom minor collaterals were missed at the initial operation. Collaterals developed in two patients during therapy. Leakage from the balloon occurred in two patients after 5 and 12 months. Two patients developed thrombosis of the hepatic artery during therapy due to the cuff being placed too tightly around the vessel. A complete remission was demonstrated in one patient with HCC, a partial response in three patients (one HCC and two metastatic), stable disease in two patients, and progression in five patients. Median survival for colorectal lesions was 15 months (range, 2 to 23 months) from start of the occlusions. Four of nine patients developed calcifications of their lesions during therapy. One patient with HCC was alive and free of disease 18 months after the start of the occlusions. Both patients with HCC had an obstructed portal vein which may have contributed to the favorable outcome. The occluder was uniformly accepted by the patients who were able to do their occlusions at home.

Adult