Susceptibility to cerulein-induced pancreatitis in inducible nitric oxide synthase-deficient mice.

Production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been proposed as a pathogenic factor in acute pancreatitis, but its role has still not been fully examined. The present study explored the role of iNOS in cerulein-induced acute pancreatitis using iNOS-deficient mice. Twelve- to 14-week-old male mice (C57B1/6 and iNOS-deficient) were administered cerulein by intraperitoneal (i.p.) injection at hourly intervals for 7 hours and killed 24 hours later after the first dose. Pancreatic wet weight, pancreatic myeloperoxidase (MPO) activity, and levels of plasma nitrite and serum amylase were measured. In another experiment isosorbide dinitrate (an NO donor) was given by oral gavage every 6 hours for 24 hours beginning simultaneously with cerulein injections in iNOS-deficient mice. Cerulein administration dose-dependently increased pancreatic wet weight, myeloperoxidase activity, and levels of nitrite and amylase in C57B1/6 mice. These parameters (except nitrite levels) were significantly intensified in iNOS-deficient mice. At the dose employed, cerulein failed to increase nitrite levels in iNOS-deficient mice. The susceptibility to cerulein toxicity in iNOS-deficient mice was abolished by NO donor treatment. NO release from an iNOS source appears to play a protective role in cerulein-induced pancreatitis. At least in part, NO may prevent neutrophil accumulation after cerulein administration.

Vagal hyperactivity in stress induced gastric ulceration in rats.

Indirect evidence suggests that stress ulceration is provoked by vagal hyperactivity. However, direct evidence of hypervagal activity during stress conditions is lacking. Experiments were designed to directly measure vagal activity under different stress conditions in rats. Starvation stress for 48 h did not change the mean amplitude of action potentials, but their frequency was significantly decreased. Restraint stress at 22 degrees C increased vagal activity, both amplitude and frequency, in the first 60 min; these responses were markedly enhanced by cold (4 degrees C) and persisted for at least 2 h. Starvation for 48 h did not induce any gastric mucosal lesions. Restraint alone produced petechiae in the gastric mucosa, but cold restraint induced severe haemorrhagic ulcers. It is concluded that cold restraint stress provokes a prolonged vagal hyperactivity, which is one of the causative factors for gastric ulceration.

A correlative study on serum cholylglycine levels in hepatobiliary disease.

The serum cholylglycine (CG), alanine aminotransferase (ALT) and total bilirubin levels were studied in 210 patients with hepatobiliary disease and in 70 healthy subjects. Serum CG concentrations in all the hepatobiliary diseases were found to be significantly higher than those of their controls. Patients with abnormal increases in ALT and bilirubin levels also showed raised CG concentrations; however, some patients with normal ALT and bilirubin levels, still had markedly elevated CG values. Patients with hepatic cirrhosis had high serum CG levels, followed, in descending order, by chronic active hepatitis and chronic persistent hepatitis. In the cholecystitis and cholelithiasis cases, their CG levels were significantly higher than those of the controls but lower than the values in hepatic disease patients; however, more cholecystitis cases had abnormally high serum bilirubin levels than CG. The results also show that serum CG concentrations vary in the different hepatobiliary diseases, and that serial CG measurements are more sensitive than measuring ALT and bilirubin levels in the diagnosis of hepatic diseases. Serum CG can be used as an index for evaluating the activity of chronic hepatitis; it can also be employed as a diagnostic tool in cholecystitis and cholelithiasis.

Cutaneous germinal center cell-derived lymphomas. A clinical histopathological and immunopathological study of 18 cases.

Eighteen cases of cutaneous germinal center cell-derived lymphomas (CGCCL) were classified into 3 types according to Kiel classification: centrocytic lymphomas (CC), 7; centroblastic-centrocytic lymphomas (CB/CC), 9; and centroblastic lymphomas (CB), 2. The duration of the disease was 3-14 months (median 9.5 months) after the first admission. In all cases, monomorphous cutaneous nodules were found as the initial manifestation of the disease. Twelve cases of CGCCL, especially those of CB and CB/CC, initially presented with normochromic anemia, a finding which is helpful in the diagnosis of the disease. Cytomorphologically, CB tumor cells were easily identified, white CC cells were hard to distinguish from the cells of nonepidermotropic cutaneous T cell lymphoma. In many cases, however, electron microscopic examination and cytochemical stains of skin biopsy tissue imprints are useful in diagnosing CGCCL. Immunoenzyme labelling (ABC method) with monoclonal antibodies indicated that B1, K and lambda positivity are very important markers for CGCCL. Our findings also showed a higher percentage of rK type in CGCCL as compared to the Western countries.