Potentiation of carbon tetrachloride-induced liver damage by dibutylyl-3',5'-cyclic AMP in unstarved rats

It has been reported that carbon tetrachloride-induced liver damage is potentiated by starvation partly due to fat accumulation in the liver and a decrease in hepatic reduced glutathione concentration and that dibutylyl-3′,5′-cyclic AMP (DBcAMP) affects fuel metabolism and decreases hepatic reduced glutathione. We investigated the effects of DBcAMP on carbon tetrachloride-induced liver damage both in unstarved and starved rats. In unstarved rats, intraperitoneal administration of DBcAMP potentiated an increase in serum alanine aminotransferase activity and fatty vacuolization in the liver, both of which were induced by carbon tetrachloride. Hepatic reduced glutathione concentration was also reduced by DBcAMP, although the change was not significant. In contrast, the administration of DBcAMP in starved rats did not affect carbon tetrachloride-induced changes in serum alanine aminotransferase activity, histological alterations and hepatic reduced glutathione concentration. Administration of DBcAMP to control rats induced different responses in unstarved control rats compared with starved control rats: in unstarved rats, blood glucose concentration decreased but serum free fatty acid concentration increased, whereas in starved rats, blood glucose concentration increased and serum free fatty acid concentration decreased. It was suggested that DBcAMP potentiated carbon tetrachloride-induced liver damage in unstarved rats, probably due to hepatic fat accumulation and a decreased hepatic reduced glutathione concentration. The former could increase the affinity of the liver for carbon tetrachloride and the latter could accelerate carbon tetrachloride-induced lipid peroxidation. It was also suggested that DBcAMP failed to affect carbon tetrachloride-induced liver damage in starved rats, probably because starvation had already decreased hepatic glutathione concentration and DBcAMP had different effects on fuel metabolism compared with effects observed in unstarved rats.     

PORTAL HAEMODYNAMICS AND HEPATIC BLOOD FLOW

Abstract Obstructive jaundice was produced in adult mongrel dogs by cholecystectomy and ligation of the common bile duct. Two weeks later 40% hepatectomy was performed during 10 min occlusion of hepatic inflow (group I). Liver tissue lipid peroxide levels increased significantly and superoxide dismutase activity decreased. The portal endotoxin (Et) concentration increased markedly after reperfusion and peripheral blood Et and serum β- N-acetyl hexosaminidase levels increased markedly, beginning 3 h after reperfusion. The phagocytic index increased transiently after reperfusion, but decreased markedly thereafter. Hepatocyte degeneration and necrosis became severe, intestinal villi were damaged and the 1 week survival rate was 23.1%; deaths were due to liver failure. These changes were prevented by construction of a portosystemic bypass and a 1 week survival rate of 70% (group II) was achieved. When the ischaemic time was prolonged to 20 min with the portosystemic bypass (group III), the pathological changes resembled those seen in group I, although no changes were observed in portal or peripheral blood Et levels. These findings suggest that major hepatectomy in the presence of severe jaundice should be carefully performed so that the ischaemic time is minimized during portosystemic bypass in an attempt not only to prevent production of Et in portal venous blood due to intestinal congestion, but also to reduce ischaemia-reperfusion injury.     

A tumor necrosis factor (TNF) receptor fragment attenuates TNF-α- and muramyl dipeptide-induced sleep and fever in rabbits

It is hypothesized that tumour necrosis factor (TNF) is an endogenous substance involved in sleep responses occurring during bacterial infection. If this hypothesis is correct, then blocking endogenous TNF, using a TNF inhibitor, should attenuate the bacterial cell wall-derived, muramyl dipeptide (MDP)-induced sleep. To test this hypothesis, the effects of intracerebroventricular (i.c.v.) injection of a TNF inhibitor, a biologically active fragment of the soluble TNF 55 kDa receptor (TNFRF), on TNF-α- and MDP-induced sleep were determined in rabbits. I.c.v. injection of 250 ng human recombinant TNF-α- or 150 pmol MDP increased non-rapid-eye-movement sleep (NREMS), decreased rapid-eye-movement sleep (REMS), enhanced electroencephalogram slow-wave activity (SWA) during NREMS and induced fever. Pretreatment of rabbits with 25 μg of the TNFRF significantly inhibited TNF-α- and MDP-induced sleep and fever responses. Finally, intravenously (i.v.) injected MDP enhanced NREMS, suppressed REMS, enhanced SWA, and induced fever; pretreatment of animals with the TNFRF injected centrally attenuated i.v. MDP-induced sleep responses but not fever. These results suggest that the TNFRF acts as a TNF-α antagonist in vivo and support the hypothesis that MDP-induced sleep is partially mediated via brain TNF-α.     

STRUCTURAL STUDIES ON STEM BROMELAIN

Stem bromelain was cleaved with cyanogen bromide, and the products were fractionated with and without prior maleylation and sulfitolysis. The fragments that corresponded to the carboxyl-terminal half of the molecule were isolated and nearly completely sequenced. This portion of the enzyme molecule contained one disulfide linkage. A specific cleavage at the amino peptide bonds of that cystine residue by reduction, modification into S-cyano derivatives and exposure to alkali gave important information of the amino terminal sequence. By combining the present data with the previously known partial sequence of the parent molecule, 101 amino acid residues were aligned down to the carboxyl terminus and compared with those of papain. The sequence homology between carboxyl-terminal halves of these two thiol proteases of plant origin was found to be 34.7%.     

Cellular and Structural Atypia of the Early Colorectal Cancers

Cellular and structural gland atypia in lesions of early colorectal cancer removed by endoscopic polypectomy in 101 patients were histopathologically studied. The following results were observed. Cellular atypia was frequently found in lesions with a high rate of nuclear polarity loss and multiple nuclear mitoses (99. 0%). The most frequent findings in the glands with structural atypia was intraglandular glands and crowding of neoplastic glands (85. 1%). Most of the appearances of the cellular and structural atypias showed no marked relationship with the sizes of the lesions, depth of invasion and association of adenoma components. Early cancer had both cellular and structural atypia in 95% of the patients and could be diagnosed by conventional histopathological criteria. However five patients with early cancer showed no structural atypia and were diagnosed as having cellular atypia. These cancers were early intramucosal cancer and four lesions were associated with adenoma components 20 mm or less in size. The loss of nuclear polarity and nuclear pleomorphism may be considered more important than nuclear stratification and mitoses in the diagnosis of early cancer.     

Application of a Circular Polarizing Device to an Electronic Endoscope for the Purpose of Prevention of Catch-Light Phenomenon

Abstract: In recent years the electronic endoscope has been increasingly used by medical practitioners in Japan. However, it has been noted that the problem of too strong light refection, which, not only hampers the procedure but also causes eye exhaustion, at the same time making photographic or computerized image processing difficult, is more frequently experienced and is more serious in magnitude when compared with using a conventional fiberoptic endoscope (catch-light phenomenon). In order to ameliorate this problem the authors experimented with the use of circularly polarized light. The combined use of a circular polarizing device to the efferent light path and a filter which blocks certain types of Circularly polarized light to the afferent path has proved to be very effective in eliminating the incidence of catch-light troubles, thus making the endoscopic procedure smooth and efficient.     

Diagnostic Significance of Two Fetal Proteins, {alpha}f and r{beta}s, in Hepatoma and Other Neoplastic Diseases

Incidences of f and rßs components were studied inserum samples from patients with various malignant and non-malignantdiseases. With the micro-Ouchterlony method, af was detectedexclusively in cases of hepatocellular carcinoma of which theincidence was 83.5%, whereas the incidence of rßswas 47.7%. However, rßs was also detected in somemalignant disease other than hepatocellular carcinoma, withan incidence of 16.5%, and was also detected in a small numberof cases of non-neoplastic liver diseases. Though not tumor-specific, rßs as one of the fetalserum proteins can be detected in cases of non-f-producing hepatomaand in cases of malignancies other than hepatoma. Thus, thedetection of this protein may be of diagnostic significance.Possible mechanism of the appearance of this protein in theblood was discussed.     

Preliminary Phase II Study of Adriamycin (ADM) in Patients with Non-Small Cell Lung Cancer (NSCLC)

A phase II study of adriamycin (ADM) (60 mg/m² was performedin 22 patients with non-small cell lung carcinoma (NSCLC). Therewere no responders in the 19 evaluable patients (16 with adenocarcinoma,two with squamous cell carcinoma and one with large cell carcinoma).The major side effects were alopecia (89%), leukocytopenia (73%),thrombocytopenia (58%) and upper gastrointestinal symptoms. Although ADM at 60 mg/m² did not appear to have sufficient antitumoractivity against NSCLC in this study, it is necessary to evaluatefurther the efficacy of ADM against NSCLC with another treatmentschedule.