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Biomedical subjects

W J Kort

Publications and source records attributed to W J Kort.

At least 37 records · Page 2Linked to original sources

Effect of fibrin sealant on the healing colonic anastomosis in the rat.

Fibrin adhesives have been advocated as a protective seal in colonic anastomosis to prevent leakage. In order to assess the effect of fibrin glue sealing we compared the healing of sutured colonic anastomosis in the rat (group 1) with the addition of human-derived fibrin sealant (group 2). As a control for a possible reaction to foreign protein, in group 3 the sutured anastomosis was sealed with specially prepared rat fibrin adhesive. On days 2, 4 and 7, ten animals in each group were killed. Adhesion formation was scored and the in situ bursting pressure was measured. The collagen concentration and degradation were estimated by measuring hydroxyproline. Adhesion formation was significantly increased in groups 2 and 3 compared with the control group. On days 2 and 7 the bursting pressure was not different between the groups. On day 4 the bursting pressure in groups 2 and 3 was significantly lower than in group 1 (P less than 0.001). These findings correspond with the results of collagen measurements. On day 4 the concentration of hydroxyproline was significantly reduced in groups 2 and 3. Histological examination showed infiltration of neutrophilic granulocytes into the sealant on days 2 and 4; on day 7 the sealant had vanished. From these results it is concluded that fibrin sealing of the colonic anastomosis in the rat does not improve healing, as demonstrated by bursting pressure and hydroxyproline concentration. On the contrary, it seems to have a negative influence.

Anastomosis, Surgical↗

Water-jet-cooled Nd:YAG laser coagulation: selective destruction of rat liver metastases.

The photocoagulating properties of the water-jet-cooled Nd:YAG laser (1,064 nm) have been studied in a rat tumor model. A colon carcinoma CC531 was implanted in the liver; 20 days after inoculation, laser therapy was performed with 600 J, 850 J, 1,200 J, 1,700 J, or 2,400 J at a power setting of either 10 or 20 W. Liver damage was determined in tissue specimen on day 1 after treatment and by serum levels of alanine aminotransferase and aspartate aminotransferase on day 1 and 2. Tissue specimen of day 36 were used to evaluate tumor remission. Liver function was assessed by antipyrine clearance on day 2. Light microscopic examination on day 1 showed coagulative necrosis up to 10 mm in diameter at 1,700 J and 20 W. At 20 W, liver damage was 22% larger than at 10 W (P = 0.0001). A significant relationship was found between laser energy and liver damage with complete tumor destruction in all animals at 2,400 J. No deterioration in liver function was found. The results of this study show the ability of the water-jet-cooled Nd:YAG laser to produce tumor coagulation necrosis with minor liver damage.

Adenocarcinoma↗

Temporary intraabdominal cryptorchidism in the weanling rat leads to irreversible azoospermia.

To study surgical reversibility of intraabdominal cryptorchidism, a study in which weanling rats were made artificially cryptorchid was undertaken. At the same time both sperm ducts were anastomosed into the urine bladder (vasocystostomy) to enable sperm output measurements, which were performed by putting the animals in metabolic cages for 24 hr. Group I animals were reoperated on 2 weeks after the initial cryptorchidism operation to reverse this intervention by an orchiopexy operation; in Group II orchiopexy was carried out after 4 weeks, in Group III after 8 weeks. In Group IV, a control group in which only the vasocystostomy operation was performed, the rats were sham operated. The animals were followed for 3 months after orchiopexy. All control animals showed sperm output between 20 and 30 million of spermatozoa per 24 hr from the age of 13 weeks on. However, experimental animals that had been de facto cryptorchid did not show any sperm output. Three out of 4 animals in which spontaneous descent of one or both testes had taken place showed sperm output from 6 to 8 weeks after orchiopexy. The results show that, notwithstanding the short periods of cryptorchidism, certain irreversible changes had already developed.

Abdomen↗

Dietary fatty acids and kidney transplantation in the rat.

In five groups of 15 rats allogeneic kidney transplantations were performed. Four groups received pre- and postoperatively a semisynthetic diet, isocalorically but differing in quantity and quality of fatty acids: group I received a diet high in saturated fat; group II, a diet high in linoleic acid; group III, a diet containing fish oil; group IV, a diet high in monoenoic acid. Finally, the fifth group of rats was fed a standard commercial chow and served as a control for the procedure of technique and immunological regimen. All groups received the same immunosuppressive regimen of immunological enhancement induced by pretreatment with complete donor blood. Survival and several parameters of graft function were studied. The results showed that the technical mortality, i.e. animals dying in the first week after transplantation, was substantially higher in rats on the semisynthetic diets in comparison with the group of rats on the commercial diet. A statistically significant better graft function could be observed in the group of rats on the diet high in linoleic acid in the first period after kidney transplantation, compared to the other groups on semisynthetic diets. This difference disappeared in the course of the study when a number of animals was lost due to graft rejection. Furthermore, in the same diet group mortality due to rejection was significantly decreased as well.

Animals↗

Photodynamic therapy for gastrointestinal tumors.

Photodynamic therapy is based on the administration of a compound that is preferentially accumulated by a tumor and which causes tumor destruction after exposure to light of a specific wavelength. The photosensitizers most commonly used in treating tumors of the gastrointestinal tract are porphyrins--hematoporphyrin derivative and dihematoporphyrin ether. These compounds have been used with success to produce reduction in tumor size of esophageal, gastric, and colorectal cancers. In some instances long-lasting complete remission have been observed after photodynamic therapy. New developments include photosensitizers that react to light of a longer wavelength, which is able to penetrate tissue to a greater depth, the use of 5-aminolevulinic acid, which is preferentially converted to porphyrin in malignant cells, and combination of photodynamic therapy with thermic laser, radiotherapy, or chemotherapy.

Colorectal Neoplasms↗

The formation of thromboxane B2, leukotriene B4 and 12-hydroxyeicosatetraenoic acid by alveolar macrophages after activation during tumor growth in the rat.

Pieces of tumor tissue were implanted subcutaneously in the right flank of BN female rats. After 3, 7, 10, 12, 14 and 17 days the lungs were lavaged and the alveolar macrophages collected. The cells were activated with the calcium ionophore A23187 and the formation of thromboxane B2 (TxB2), leukotriene B4 (LTB4) and 12-hydroxyeicosatetraenoic acid (12-HETE) determined. The formation of TxB2 decreased considerably until day 7. Thereafter, no changes occurred. The formation of LTB4 increased after the tumor implantation until day 10 and remained stable for the rest of the period, 12-HETE formation was approximately similar, with a decrease at day 12 but continued to increase after day 14. These results suggest that during tumor growth an inhibition of the cyclo-oxygenase or thromboxane synthase occurs and an activation of the C5- and C12-lipoxygenases of the alveolar macrophages.

Adenocarcinoma↗

Significance of thromboxane A2 and prostaglandin I2 in acute necrotizing pancreatitis in rats.

Plasma thromboxane concentrations were found to be significantly elevated in acute necrotizing pancreatitis in rats, whereas prostaglandin I2 levels were not. The significance of these alterations was investigated. Pancreatitis was induced by injecting 5% sodium taurocholate into the pancreatic duct. Iloprost (ZK 36374, a stable analog of prostaglandin I2, 25 ng/kg body weight) decreased the mortality rate from 100% to 50%. When treatment with iloprost was combined with simultaneous administration of either Sibelium (flunarizine R 14,950, 0.2 mg/kg body weight) or dazmegrel (UK 38,485, 50 mg/kg body weight) an additional decrease in the mortality rate was recorded. Dazmegrel is a selective thromboxane A2 synthetase inhibitor and flunarizine (a calcium entry blocker) also inhibits the effects of elevated thromboxane A2 levels. With flunarizine and iloprost the mortality rate was 40% (P less than 0.05); with dazmegrel and iloprost it was 10% (P less than 0.01). The results of the present study suggest that thromboxane A2 and prostaglandin I2 play a role in the course of acute necrotizing pancreatitis.

Acute Disease↗

Improvement in blood flow and diameter of the postanastomotic rat tail artery by topical application of lidocaine in varying concentrations.

Prolonged spasm in small vessels is a major problem after microsurgical procedures. Topical agents applied to resolve these spasms have been the subject of many experimental studies. In this model we studied the effectiveness of various concentrations of lidocaine in resolving microvascular spasms induced by anastomosing the ventral rat tail artery.

Administration, Topical↗

Eicosanoid profile of healing colon anastomosis and peritoneal macrophages in the rat.

Because intraperitoneal administration of prostaglandin E2 (PGE2) has a negative influence on the healing of colonic anastomosis, the production of eicosanoid products in the healing rat colon after resection and anastomosis was studied using high performance liquid chromatography. Normal colonic tissue metabolizes small amounts of arachidonic acid into cyclo-oxygenase and lipoxygenase products. After construction of an anastomosis, however, there is increased production of lipoxygenase products, while cyclooxygenase activity remains low. Increased amounts of PGE2 and other cyclo-oxygenase products are not produced after anastomosis of the colon and probably do not play a major role in uncomplicated healing of the large intestine in the rat. During the first eight days of repair in the anastomosed colonic tissue, a statistically significant increase in 12-hydroxyeicosatetraenoic acid (12-HETE) production was found compared with control colon tissue (p = 0.001). At the same time peritoneal macrophages from these rats showed increased 12-HETE production. Eicosanoid synthesis of peritoneal macrophages resembled eicosanoid synthesis of anastomosed colon taken from the same rat indicating that 12-HETE, in particular, may be of macrophage origin.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Artificial intra-abdominal cryptorchidism in young adult rats leads to irreversible azoospermia.

To study reversibility of artificial intra-abdominal cryptorchidism, in four groups of 5 rats at 3 months of age vasocystostomies (a microsurgical operation anastomosing both sperm ducts into the urine bladder) were carried out. This procedure enables sperm output measurements, which was performed by putting the animals for 24 h in metabolic cages. Four weeks later 15 of the remaining animals were operated again to induce artificial cryptorchidism. In a fourth group, 3 animals were sham-operated only, leaving the testes in place. Two weeks later in the animals of group I cryptorchidism was reversed by an orchiopexy operation; in group II orchiopexy was carried out after 4 weeks, in group III after 8 weeks. In group IV the animals were sham-operated again. Evaluation of sperm output took place for 3 months after orchiopexy. In the 1st week after vasocystostomy the animals showed a large variation in sperm output, but 2 weeks later, all animals had sperm output between 30-60 x 10(6) of spermatoza/24 h. Immediately after cryptorchidism sperm output decreased dramatically, and 2 weeks later all animals were azoospermic, except for sham-operated controls. After orchiopexy not one of the experimental animals showed any return of spermatozoa. We concluded that intra-abdominal cryptorchidism soon leads to irreversible damage to the testes resulting in azoospermia.

Animals↗

Eicosanoid synthesis by alveolar macrophages in rats with malignant mammary tumors: differences in rats treated with and without carrageenan implants.

Eicosanoid synthesis by alveolar macrophages (AM), harvested from tumor bearing animals, was measured after tumor inoculation in rats treated with or without carrageenan (carra), an immunomodulating agent. After incubation of the cells with [14]C-arachidonic acid and the Ca-ionophore A23187, samples were measured by high pressure liquid chromatography (HPLC). From the HPLC profiles the lypoxygenase products, 12-hydroxyeicosatetraenoic acid (12-HETE), 15-HETE, and leukotriene-B4 (LTB4) were determined as well as the cyclooxygenase products, prostaglandin (PG)E2, PGF2 alpha and TXB2. After tumor inoculation AM-synthesis of lipoxygenase products tended to increase to values twice those of the base line values, whereas cyclooxygenase products showed subnormal values. In the non treated animals, 10 days after tumor inoculation, statistically significant increases in 12- and 15-HETE, LTB4 and PGE2 were observed when compared with carra treated animals. Later measurements did not show these differences in AM metabolism. AM metabolism was (negatively) correlated with the number of macrophages, which was particularly evident in the correlation with 12-HETE synthesis.

Animals↗

Significance of prostaglandin E2 in acute necrotising pancreatitis in rats.

Acute necrotising pancreatitis in rats was induced by injecting 5% sodium taurocholate into the pancreatic duct. Prostaglandin E2 (100 micrograms/kg subcutaneously twice) decreased the mortality rate from 100% to 60% (NS). When treatment with prostaglandin E2 was combined with simultaneous administration of either dazmegrel (UK 38,485, 50 mg/kg bodyweight) or Sibelium (Flunarizine R 14,950, 0.2 mg/kg body weight) a significant decrease in the mortality rate (p less than 0.05) was recorded. Dazmegrel is a selective thromboxane A2 synthetase inhibitor and prevents the formation of thromboxane A2. Flunarizine (a calcium entry blocker) decreases thromboxane A2 formation and also inhibits the effects of raised thromboxane A2 concentrations. As plasma thromboxane B2 (the stable metabolite of thromboxane A2) concentrations increase and the plasma prostaglandin E2 concentrations decrease in acute necrotising pancreatitis in rats, the results of the present study indicate that these prostaglandins play a role in the pathophysiology of the disease. It is suggested that restoration of the balance in prostanoid concentrations will have a beneficial effect on the course of acute necrotising pancreatitis.

Acute Disease↗

A new method of sampling ascitic fluid from rats.

A new method of sampling ascitic fluid from rats over a period of at least 8 h in a reliable and easy way is described. The objective was to determine drug concentrations in ascitic fluid after intraperitoneal chemotherapy. Two silicon tubes were implanted into the abdominal cavity, one for drug administration and regulation of pressure, the other enabled ascitic fluid to be withdrawn.

Animals↗

Plasma eicosanoids and platelet aggregation as parameters to monitor tumor patients. A study in 12 healthy subjects to obtain baseline levels.

Plasma levels of the eicosanoids PGE2, 6k-PGF1 alpha and TXB2 as well as platelet aggregation were determined in 12 healthy subjects, aging 23-50. It was our assumption that the parameters could be of use to monitor cancer patients, provided that the results of the determinations could be well reproduced and that the variation within a healthy population was small. In a group of laboratory employees (6 males and 6 females) blood samples were taken, 3 times, with a 2 week interval, under controlled conditions. Drug ingestion was recorded, and taken into account for the evaluation. The ranges of plasma eicosanoid, and of in vitro platelet aggregation values were large. The variation in both parameters was in large part due to intra-individual variation (based on the different values obtained in one subject). In part however, the variation could be traced to ingestion of non steroidal anti inflammatory drugs (NSAIDs). The following abbreviations were used: NSAID = non steroidal anti inflammatory drug, PGE2 = prostaglandin E2, 6k-PGF1 alpha = 6-ketoprostaglandin-F1 alpha, TXB2 = thromboxane B2, TXA2 = thromboxane A2, PGI2 = prostaglandin I2 = prostacyclin, RIA = radio immuno assay, ADP = adenosine diphosphate.

Adult↗

Raised plasma thromboxane B2 levels in experimental acute necrotizing pancreatitis in rats. The effects of flunarizine, dazoxiben, and indomethacin.

The possible role of thromboxane A2 (TXA2) in acute necrotizing pancreatitis (ANP) was investigated in rats. After ANP was induced by injecting sodium taurocholate (5% w/v) into the pancreatic duct, the thromboxane B2 (TXB2) levels in plasma increased significantly. The effects of indomethacin, a general blocker of prostaglandin synthesis, on survival time and on plasma TXB2 levels were compared with those of dazoxiben, a more specific blocker of TXA2 synthesis, and Flunarizine, a calcium entry blocker known to inhibit the effects of TXA2. In a test group without any treatment, all animals died within 30 h of ANP induction. Although TXB2 levels were lowered by the administration of indomethacin, dazoxiben, and Flunarizine, survival times were not significantly altered. Indomethacin pretreatment had no beneficial effect, whereas 30% and 40% of the animals survived for 36 h after treatment with Flunarizine and dazoxiben, respectively. The results of the present study indicate that inhibition of TXA2 synthesis alone does not dramatically alter survival time. However, a potential role for other arachidonate metabolites in ANP cannot be ruled out by this study.

Acute Disease↗

Prostanoid imbalance in experimental acute necrotizing pancreatitis in rats.

In an investigation of the pathogenesis of acute necrotizing pancreatitis (ANP) the plasma levels of TXB2, 6-keto-PGF1 alpha, and PGE2 were measured in rats. After induction of ANP by injection of 5% sodium taurocholate into the pancreatic duct, a marked increase in TXB2 levels and a slight increase in 6-keto-PGF 1 alpha levels were found. PGE2 levels decreased. Mortality was 100% within 30 h. Pretreatment with chloroquine, a phospholipase A2 inhibitor, led to a inhibition of TXB2 production, whereas 6-keto-PGF1 alpha and PGE2 levels showed a surprising slight elevation in the first 6 h. Pretreatment with chloroquine decreased mortality by 30%. Pretreatment with FPL 55712, a leukotriene synthesis blocker, caused an increase in TXB2 and PGE2 levels, whereas the formation of 6-keto-PGF1 alpha remained unaltered. Two out of nine animals survived after pretreatment with FPL 55712. The results of the present study indicate that arachidonate end products are involved in ANP. The significance of the high TXB2 levels, decreased PGE2 levels, and only slightly elevated 6-keto-PGF1 alpha levels during ANP requires further investigation. The thromboxane A2 to prostacyclin ratio may be important.

6-Ketoprostaglandin F1 alpha↗

Role of alveolar macrophages in tumor-bearing rats: tumoricidal properties of carrageenan-activated macrophages.

Tumor BN472, a malignant mammary adenocarcinoma, was subcutaneously transplanted into syngeneic female Brown Norway rats. Seven days after tumor inoculation, carrageenan-impregnated synthetic sponges were subcutaneously implanted in control and tumor-bearing rats. Another week later the animals were sacrificed and alveolar macrophages were harvested and tested for tumoricidal activity against a tissue culture line of BN472 cells and their capacity to phagocytose formaldehyde-treated sheep erythrocytes. The data demonstrate that carrageenan statistically significantly enhances the tumoricidal activity of alveolar macrophages in tumor-bearing rats. Phagocytic activity of the macrophages in these animals is not different from sham-operated control animals, whereas the phagocytic activity of tumor-bearing rats is statistically significantly decreased.

Animals↗