Effect of short-term-ischemia and reperfusion on the rat pancreas]

In order to examine the toxic effects on the pancreas of oxygen free radicals which are generated at reperfusion after ischemia, a short term-ischemia/reperfusion model was prepared in rats. Both the anterior mesenteric artery and the celiac artery were ligated and then released to restore blood flow. In a group where the anterior mesenteric and the celiac arteries were ligated for 60 minutes, the serum levels of amylase and lipase rose 7 and 6 times, respectively, 7 hours after reperfusion. In a group ligated for 30 minutes, both levels remained unchanged. Histologically, vacuolization of the pancreatic acinar cells was observed, only in a group rats ischemic for 7 hours. In rats ligated for 60 minutes with a continuous venous infusion of superoxide dismutase (SOD) (3600 U/Kg/hour), the secretion of amylase and lipase decreased to 25 percent of that in the non-injected group. These results confirm that the oxygen free radicals, which are generated by the short term-ischemia/reperfusion method, injure the pancreas. This may lead to pancreatitis with hyperamylasemia and hyperlipasemia. Pretreatment with an active oxygen scavenger, SOD, markedly reduces the rise in serum amylase and lipase levels. This suggests that active oxygen free radicals are involved in the pathogenesis of acute pancreatitis.     

Short-term toxicity study of 4-dimethylaminoazobenzene in marmosets

The marmoset, a small non-human primate, has rarely been used in toxicological studies. A short-term toxicity study was performed on common marmosets (BW = 330 +/- 32 g). Fifteen male marmosets received oral administration of DAB at a dose level of 56 mg/kg/day and 4 control animals received corn oil alone for a period of 15 days. Hematological, biochemical, histopathological and bone marrow examinations were carried out on the 5th, 10th and 15th day of treatment. Body weight decreased continuously and two animals died on day 10. Decreases in RBC, Hb and Ht and increases in MCV and WBC were observed. Uric acid and glucose were increased and AlP and LAP were decreased. Aldolase, GOT and GPT were increased by day 10, and thereafter recovery of aldolase to the control level and decreases of GOT and GPT were observed. Relative organ weights of the liver, kidney, spleen and adrenal were increased. Histologically, C-cell hyperplasia of the thyroid and slight changes of the liver were noted. Marrow total cell counts were not changed, but the G/E ratio was reduced. Thus, macrocytic anemia, an increase of marrow erythroblasts due to anemia and changes of biochemical parameters indicating liver injury were observed in marmosets; these findings were similar to those in rats in the previous experiments.     

Lung carcinosarcoma

Lung carcinosarcoma is a neoplasm of high grade composed of epithelial and mesenchymal cells. It is exceptional; and usually affects men who are smokers, between the fifth and eighth decades of life. Medical treatment, chemotherapy and radiotherapy are not active in this kind of tumour, so surgery is the treatment of choice. Prognosis is poor with survival rates at 6 months around 27%. We describe the diagnostic process and the clinical outcome of a patient with lung carcinosarcoma with several paraneoplastic syndromes.     

Comparative study on various combination chemotherapies against human gastric cancer xenograft lines of well- and poorly-differentiated adenocarcinomas transplanted in nude mice.

Two human gastric cancer xenograft lines (GC-YN and GC-SF) transplanted in nude mice were employed to evaluate and compare the anticancer effect of seven single anticancer agents and their various combinations. Mitomycin C, cisplatin (Briplatin) (CDDP) and 5-fluorouracil (5-FU) were screened out to be effective against GC-YN and only epirubicin (Farmorubicin) (EPIR) was effective against GC-SF. Combinations of two of these 'effective' agents revealed that FP (5-FU + CDDP) is the most effective two-agent combination regimen against both lines, and some of those 'ineffective' single agents showed synergistic effects against both lines when combined with 5-FU. Moreover, three-agent combinations composed of FP and one of the other five agents were also evaluated to select out the most effective regimen. All the combinations showed higher inhibition on the tumor growth of GC-YN than FP regimen, and FP + adriamycin (Adriacin) (ADR) and FP + EPIR were more effective against GC-SF than FP. However, taking toxic effects into consideration, the results suggest that CDDP + 5-FU + EPIR (FPEPIR) may be the regimen most worthy of clinical trial in the chemotherapy against human gastric cancer.     

Indices of the malignancy of cancer--is it possible to predict the recurrence or metastasis of cancer?

The following 3 points are important clinical problems to be resolved in the management of cancer: 1. Are there any useful procedures in the diagnosis, treatment or prevention of recurrence or metastasis of cancer? 2. Can the recurrence or metastasis of cancer be predicted? 3. Are there any parameters which reflect the degree or grade of malignancy of cancer? For the diagnosis of recurrence or metastasis, tumor markers and imaging MRI are useful, especially for colorectal cancer. Radical extended resection can lead to good survival even though the tumor recurs. A randomized prospective study of 1011 gastrectomized cancer patients treated with oral OK432 showed significantly good results, especially in n(+) cases with curative resection. Prognostic stratification and risk assessment by computer analysis using Akaike Information Criteria (AIC) showed that cancerous invasion of subserosal veins (Vd) was the most important risk factor for liver metastasis of colorectal cancer. In predicting the recurrence or metastasis of cancer computer analysis by AIC appears to be a useful procedure. DNA ploidy patterns demonstrated by flow cytometry and oncogene analysis of tumor tissue have been reported and discussed as possible indices of the grade of malignancy.     

The effect of partial hepatectomy on glucose-stimulated insulin release from the isolated perfused pancreas in rats

To investigate the functional changes of endocrine pancreas in the early stage after partial hepatectomy, we evaluated the changes in the secretion of insulin to glucose load in perfused rat pancreas at 4 and 7 days after about 70% hepatectomy. Insulin responses to glucose load were significantly augmented at 4 days compared with both the normal and sham-operation rats and at 7 days also significantly augmented compared with the normal rats. These results are in accordance with the morphological changes of islet and indicate that in the early stage after hepatectomy, the response of islet B-cells to glucose load are increased in order to support the glucose metabolism in this stage. Thus, insulin seems to play an important role in the regenerating liver after hepatectomy and these changes seem to be one of the adaptation of endocrine pancreas after hepatectomy to support the regenerating liver.     

Changes in lysosomal enzyme and fragility of pancreatic acinar cells in hepatectomized rats

To explore the cellular and lysosomal fragility of pancreatic acinar cells in both the early and recovering stages after partial hepatectomy, we evaluated the changes in the pancreatic water content, redistribution of lysosomal enzyme, lysosomal fragility in acinar cells, and lactate dehydrogenese (LDH) discharge from acinar cells 4 days and 8 days after about 70% hepatectomy in rats. In the early stage (4 days) after hepatecotmy, the pancreatic water content was significantly greater than that in sham-operated or normal rats. Both the LDH discharge and lysosomal fragility were also significantly higher than those in the sham-operated and normal rats. Redistribution of lysosomal enzyme was also found in this early stage. In the recovering stage (8 days) after hepatectomy, these parameters tended to return to the preoperative levels (normal rats). These results indicate that the cellular fragility of acinar cells is increased in the early stage after hepatectomy. Lysosomal fragility seems to be related to this cellular fragility of acinar cells in the early stage after hepatectomy.     

Synthetic neuromedin C stimulates exocrine pancreatic secretion in dogs and rats

We have examined the effect of neuromedin C on exocrine pancreatic secretion both in vivo and in vitro, and compared its bioactivity with those of related peptides. In anesthetized dogs, neuromedin C caused a dose-dependent initial reduction of pancreatic blood flow and an increase in secretin-stimulated exocrine pancreatic secretion, and had almost the same potency as gastrin-releasing peptide (GRP) in decreasing pancreatic blood flow. A potent stimulatory effect on exocrine pancreatic secretion was found in conscious dogs accompanied by a significant elevation in the circulating cholecystokinin (CCK) levels. In isolated rat pancreatic acini, amylase was released dose-dependently in response to neuromedin C. This study demonstrates that neuromedin C (a smaller molecular form of GRP) possesses potent bioactivity on exocrine pancreas and suggests that two factors may be involved in the mechanism by which this peptide effects exocrine secretion, namely; direct stimulation on acinar cells and stimulation of CCK release.