Ineke M. Weijma

Healing of ischemic colonic anastomosis: Fibrin sealant does not improve wound healing

Fibrin adhesives have been advocated as a protective sealant in high-risk colonic anastomoses to prevent leakage. To assess the effect of fibrin glue sealing on the healing ischemic anastomosis, we compared the healing of sutured colonic anastomoses in the rat, with and without fibrin adhesive (Groups IA and IB), and ischemic anastomoses with and without fibrin adhesive (Groups IIA and IIB). On days two, four, and seven, 10 animals in each group were sacrificed. Adhesion formation was scored, and thein situbursting pressure was measured. The collagen concentration and degradation were estimated by measuring hydroxyproline. Adhesion formation was more prominent in Groups IB, IIA, and IIB on day four only; abscesses were noted in the ischemic group in four rats. Anastomotic bursting pressure was significantly lower in sealed (IB) and ischemic anastomoses (IIA) than in normal anastomoses (IA) on day four. Sealing of ischemic anastomoses did not change bursting pressures on days two, four, and seven. The relative decrease of collagen in the sealed anastomoses is significantly higher on day four only. It is concluded that sealing of normal colonic anastomoses in the rat has a negative effect on wound healing. Ischemia at the anastomotic site results in weaker anastomotic strength on day four postoperatively. Also in ischemic anastomoses, fibrin sealant does not improve wound healing during the first seven days. Adhesion formation on ischemic intestinal anastomoses was not prevented by fibrin sealing.

Effect of stress and dietary fatty acids on allograft survival in the rat.

To determine the immunosuppressive effect of stress and a diet rich on linoleic acid on vascularized organ graft survival in the rat, a series of allogeneic heart and kidney grafts were carried out. Restraint stress resulted in a significant prolongation of the survival time. Although 5 days of postoperative stress gave the best results, 3 h of stress given on the first postoperative day already gave a marked prolongation of the survival time of kidney allografts. The beneficial effect of stress on heart survival was abolished when prior adrenalectomy was carried out. A diet high on polyunsaturated fatty acids gave significant prolongation of the survival times of kidney-grafted rats. A diet hgh on saturated fatty acids did not result in a statistical significant prolongation of the survival time, although the difference with the polyunsaturated fatty acid group was very small and not statistically significant. It was concluded that stress and diets high in certain types of fatty acids depress the immune response in rats, possibly via a mechanism which has some common pathways. The adrenal glands could play an important role in this immune inhibition.

Growth of an implanted fibrosarcoma in rats is associated with high levels of plasma prostaglandin-E2 and thromboxane-B2

Growth of BN175, a malignant fibrosarcoma, was correlated with high plasma TXB2 and PGE2 levels. This statistically significant increase was first detected 17 days after inoculation of the tumor, at which time the tumors were 20 mms in diameter. A further increase in tumor size was associated with still higher PGE2 and TXB2 values. At the same time, progressive alterations in platelet function, as measured by ADP-induced platelet aggregation, were observed. 6-keto-PGF1 alpha levels remained normal throughout the whole experiment. It was concluded that tumor growth was associated with changes in PG synthesis and platelet function, although it remains unclear whether these changes were caused by some host immunological response towards the tumor or were predominantly the result of tumor PG-synthesis.

Reductive Effect of Phenobarbital on Graft Survival in Prednisolone-Treated Rats

This study was meant to elucidate in an animal model the results found in a clinical retrospective study, where a higher incidence of graft failure occurred when anticonvulsant therapy was given to pa

Influence of the linoleic acid content of the diet on tumor growth in transplantable rat tumor models

Diets high (17.7 cal%) and low (3.3 cal%) in linoleic acid were given to groups of Brown Norway female rats before and after inoculation of syngeneic tumor models with different characteristics, with regard to tumor spread, malignancy, immunogenicity, growth rate, rat strain, and histopathological features. Despite the differences in characteristics, in most tumor models, tumor growth was identical in both experimental groups. However, in 2 tumor models, an adrenal cortical carcinoma and a myeloid leukemia, differences in growth were noted. In rats given the diet low in linoleic acid, growth of the cortical carcinoma was significantly increased, whereas the opposite effect was seen in rats with myeloid leukemia.

Diets Rich in Fish Oil Cannot Control Tumor Cell Metastasis

Rats fed diets containing different amounts of polyunsaturated fatty acids either of the n-3 or n-6 type, received cultured, syngeneic mammary tumor (BN472) cells intravenously. Animals were sacrificed 2 weeks after tumor inoculation, and the number of pulmonary tumor foci was counted. No significant differences in the number of metastatic foci were observed between the dietary groups. Prostaglandin measurements in the supernatant of tumor cells cultured in vitro showed that the tumor cells could produce thromboxane A2. Many investigators connected this tumor synthesis capacity with tumor metastatic activity. Yet in our study, diets rich in menhaden oil, with the known capacity to inhibit thromboxane synthesis, could not control tumor metastasis in this particular tumor model.

Is the 7,12-Dimethylbenz[a]anthracene-Induced Rat Mammary Tumor Model Suitable as a Preclinical Model to Study Mammary Tumor Malignancy?

To study the biological characteristics of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in rats, 20 Sprague Dawley female rats received a single oral dose of 5 mg of this carcinogen. During the 35-week observation time 78 primary tumors were removed. While in most cases the primary tumor could be removed completely, 7 out of 20 animals eventually had to be sacrificed for inoperable local recurrence of the primary tumor. Notwithstanding, the long period of time given for tumor metastases to develop (mean time between tumor removal and termination was 18.5 weeks), tumor spread either to lungs or regional lymph nodes could not be established. This relatively benign behavior of the tumor was in contrast with the morphological characteristics of the tumor, which uniformly showed the features of adenocarcinomas. The difference in biological behavior between DMBA-induced mammary tumors in rats and malignant mammary tumors in humans suggests that as a model this system is of limited value for investigations of mechanisms of malignant behavior of human tumors.