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Biomedical subjects

S Bengmark

Publications and source records attributed to S Bengmark.

At least 19 recordsLinked to original sources

Inhibitory effect of 2-deoxy-D-glucose on liver tumor growth in rats.

Since tumor cells are more dependent on glycolysis for energy supply than other cells, we tested whether its inhibition by 2-deoxy-D-glucose (2-DG) affects tumor growth. Male Wistar rats were inoculated in the liver with tumor cells from a chemically induced colonic adenocarcinoma. From day 5 after inoculation 2-DG (400 mg/kg/24 h) was continuously infused into the hepatic artery for 5 days; controls received saline in the same fashion. Seven days after the end of infusion, the animals were sacrificed. A second experimental group of rats was treated with isolated liver perfusion for 30 min with oxygenated blood through the portal vein and hepatic artery simultaneously. In the perfusate, 400 mg/kg 2-DG were added, and the rats were sacrificed at 10 days after perfusion. A first control group underwent perfusion without 2-DG, and a second control group received i.v. infusion of 2-DG (400 mg/kg/30 min) for 30 min over 5 days. A nontreated control group was also added. All animals survived the procedures. The concentration of blood glucose increased in the rats receiving 2-DG i.v. and intraarterially but was unchanged in the other groups. The tumor growth was significantly reduced by 2-DG in all experimental groups, with no difference between the groups. It is therefore concluded that 2-DG is of potential interest in the treatment of malignancies. Since local application of 2-DG avoids the risk for systemic side effects, this approach should be explored further.

Animals

Bacterial translocation after major hepatectomy in patients and rats.

Bacterial infections are frequent complications after liver resection. Of 138 patients who underwent major hepatectomy, 11 patients (8%) developed intra-abdominal sepsis in the postoperative period. Seven bacterial strains of gut origin were isolated from the abdominal cavity. Eight patients had multiple bacteria cultured. In the experimental studies on rat models, positive mesenteric lymph node cultures were seen 2 hours after removal of 70% and 90% of the total weight of the rat liver, and 12 hours after 50% hepatectomy, persisting for 3 and 4 days after 50% and 70% hepatectomy, respectively. The incidences of bacteremia 2 and 4 hours after 90% hepatectomy were 80% and 100%, respectively; 6 hours after 70% liver resection, the incidence of bacteremia was 33%. Blood cultures were positive in only 6% of the rats following 50% hepatectomy, and in none of the controls. Thus, bacterial translocation occurs in the early course after hepatectomy, the incidence being proportional to the amount of liver tissue removed.

Abdomen

Effect of phosphatidylcholine on postoperative adhesions after small bowel anastomosis in the rat.

The possibility of preventing postoperative adhesions using phosphatidylcholine (PC) was studied in rats. A small bowel anastomosis was created using continuous or interrupted 5/0 silk sutures. Adhesions were measured by recording the maximal length of adhesions around the anastomosis and the number of organs involved in the adhesions. PC was administered intraperitoneally either as a single dose or as three separate doses. Postoperative adhesions developed in all animals; the degree of adhesion was independent of the suture technique used. PC given once at a dose of 20 mg significantly decreased adhesion formation (P less than 0.01). The mechanism underlying this effect may be that the exogenous PC provides a lubricant layer replacing endogenous hydrolysed phospholipid. The result with repeated PC administration was not different from that after a single dose. Increasing the single dose of PC to 40 or 60 mg resulted in anastomotic dehiscence and subsequent peritonitis. It is concluded that PC in a single dose of 20 mg reduces adhesion formation after small bowel anastomosis in the rat.

Anastomosis, Surgical

Effect of biliary decompression on reticuloendothelial function in jaundiced rats.

The recovery of reticuloendothelial system (RES) function following decompression of obstructive jaundice was studied using a rat model with bile duct ligation and side-to-side choledochoduodenostomy. Histopathological changes in the liver were still present 5 weeks after relief of jaundice, while results of liver function tests had returned to normal. RES function evaluated by the blood clearance and organ uptake of radiolabelled Escherichia coli using a corrected phagocytic index gradually returned to normal following biliary decompression. The severely impaired RES activity noted 1 week after operation may explain the increased incidence of sepsis and renal insufficiency in the early period after biliary surgery in jaundiced patients.

Animals

Endothelialization of microporous polytetrafluoroethylene grafts in the infrarenal aorta and caval vein of the rat.

To study healing and endothelialization of vascular grafts, microporous polytetrafluoroethylene (PTFE) prostheses 2 mm in inner diameter and 5 mm long were implanted into the infrarenal aorta or caval vein of the rat. Patency was assessed in six rats from each group at days 3, 7, 14, 28, and 56 after implantation. Four grafts were occluded, two in the aorta (56 days) and two in the caval vein (3 and 14 days). The prostheses were examined via scanning electron and light microscopy for evaluation of endothelialization. At 3 days, the inner surface of the aortic grafts was covered by a plasma proteinaceous layer and that of the caval vein grafts by a thin mural thrombus. Endothelial cells then migrated from aorta/caval vein edges over the graft. At 14 days, the caval vein grafts were completely re-endothelialized, and, at 28 days, the mural thrombus in these grafts was replaced by neointima. In contrast, endothelialization of the aortic grafts had advanced only 1 mm at about 56 days, never forming a complete endothelial layer. We conclude that endothelialization of microporous PTFE prostheses is more rapid and complete in the caval vein than in the aorta of the rat.

Animals

Effect of fermented oatmeal soup on the cholesterol level and the Lactobacillus colonization of rat intestinal mucosa.

Rats were fed with freeze-dried oatmeal soup fermented by six different Lactobacillus strains from rat and man; the formula is intended for enteral feeding. The serum cholesterol levels after 10 d were lower for rats eating oatmeal as compared to a commercial product, Biosorb Sond. Colonizing ability of the administered strains were evaluated in vivo. Only Lactobacillus reuteri R21c were able to, effectively, colonizing the mucosa; it represented about 30% of the Lactobacillus population 24 d after termination of the administration. L. reuteri R21c was easily recognized by the ability to produce a yellow pigment on agar plates. The identity was confirmed by carbohydrate fermentations (API 50CH), plasmid pattern and endonuclease restriction analysis of the chromosomal DNA.

Animals

Systematics of the Lactobacillus population on rat intestinal mucosa with special reference to Lactobacillus reuteri.

The systematics of the Lactobacillus population of the intestines of 88 different rats was studied; 80 rats had been fed on fermented oat-meal soup (Molin et al. 1992). One-hundred-twenty-two Lactobacillus strains from the intestinal mucosa were phenotypically classified together with twenty-eight reference strains of Lactobacillus and Leuconostoc, using 49 unit characters. Data were examined using Jaccard coefficient, and unweighted pair group algorithm with arithmetic averages. Two major and eleven minor clusters were defined at the 76% SJ-similarity level: Cluster 1 included thirty isolates which could not be identified further, but had resemblance to the type strains of L. jensenii, L. gasseri, L. crispatus, and to some extent to L. acidophilus. Cluster 12 including fifty-four intestinal isolates was identified as L. reuteri; and so was cluster 13 (five isolates). Isolates of the major clusters were found in all parts of the intestines. The genomic homogeneity of the L. reuteri isolates was scrutinized by endonuclease restriction analysis of the chromosomal DNA, and the isolates could be divided into six genomic strains.

Algorithms

A simple two-stage technique of total hepatectomy in the rat.

We describe a novel, two-stage technique of total hepatectomy in the rat. In the first stage, acute and progressive atrophy of the posterior liver lobes attached to the inferior vena cava is induced by selective portal venous branch ligations. Two weeks later, when these lobes comprise approximately only 3% of the total liver mass, the hepatic artery is ligated and the enlarged anterior liver lobes are resected. An end-to-side porto-caval shunt is then carried out to ensure vascular integrity of the splanchnic area. This procedure was associated with no operative mortality and glucose-supplemented animals had a mean survival time of 20 +/- 5 hr. The anhepatic state was associated with significant metabolic and biochemical changes associated with necrosis of a small residual liver parenchyma. This animal preparation is a reproducible model of the anhepatic phase of experimental fulminant hepatic failure.

Animals

A new dextran 40-based solution for liver preservation.

UW solution is at present the most efficient solution for preservation of livers for transplantation. We have developed an alternative solution based on dextran instead of hydroxyethyl starch and without raffinose, allopurinol, magnesium sulfate, insulin, penicillin, or dexamethasone, which all are used in UW solution. In addition, 62.5 mM potassium in UW solution is replaced with sodium. We tested this new solution for liver preservation using the isolated perfused rabbit liver. We found that livers preserved in the UW solution for 24 or 48 hr lost 11.6 +/- 2.6% and 16.8 +/- 2.0% of the prepreservation weight, respectively, as a sign of organ shrinkage (P less than 0.001). In contrast, no change in liver weight was observed after preservation in the new dextran-based solution. Similarly, no change in total tissue water of the rat liver slices was seen after preservation in the new solution. Furthermore, livers preserved for 24 hr in the UW solution or the new solution produced the same amount of bile as unpreserved livers. However, after preservation in the UW solution for 48 hr, bile production was reduced by 65% (P less than 0.05). In contrast, livers preserved for 48 hr in the new solution showed no reduction in bile production. We conclude that our new solution significantly improves long-term liver preservation, and with this modified solution, 48-hr preservation may be safe.

Adenosine

Collateral formation after repeated transient dearterialization of the rat liver.

Hepatic artery ligation is used for the palliation of patients with malignant liver tumours. Collaterals are developed rapidly and could to some extent explain why the growth is affected for only a short period. With intermittent dearterialization, collaterals seem to be avoided and possibly a more extended effect should be expected. The most efficient period of dearterialization to avoid collaterals was studied in this experiment. Five groups of rats were treated with daily repeated transient dearterializations for 0 (n = 3), 60 (n = 6), 120 (n = 6), 180 (n = 6) and 240 minutes (n = 6) respectively for 5 days and compared to another group (n = 3) that was permanently dearterialized. After treatment, celiac angiograms were obtained. All hepatic arteries were reliably occluded and patent after 5 days of daily blockades in all but two rats. There were no collaterals demonstrable on the angiograms in the first four groups after 5 days of intermittent obstruction of the arterial blood flow to the liver. After 240 minutes of dearterialization as well as after collaterals developed and were clearly demonstrated on the angiograms after six days. Liver enzymes were normal even after 4 hours of dearterialization. Repeated occlusions of the hepatic artery was reliably achieved with the implantable minioccluder. Repeated, transient dearterializations for 1, 2 or 3 hours could be performed without development of collaterals and without damage to the liver.

Animals

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