Gastroenterologia Japonica

To clarify the involvement of atrial natriuretic peptide (ANP) in the pathogenesis of liver cirrhosis, we measured plasma ANP in patients with various stages of cirrhosis and in age-matched normal subjects. Urinary cyclic guanosine monophosphate (cGMP) was also measured as a marker of active biological ANP. In addition, effects of exogenous synthetic human ANP (0.5 Μg/kg) on renal functions were examined in normal subjects and in cirrhotics without ascites or with mild ascites. Plasma ANP levels were not significantly different among these 3 groups. Urinary cGMP concentrations were significantly higher in both cirrhotics without ascites and cirrhotics with mild ascites, (340 pmol/ml, P<0.05 and 496 pmol/ml, P<0.01 respectively) than normal subjects (95 pmol/ml). In normal subjects, marked increases in urinary volume (UV), sodium excretion (UNaV), fraction excretion of sodium (FENa) and free water clearance (CH2O) were induced after ANP infusion, and significant recoveries were subsequently observed in these parameters. However, in cirrhotics, the responses to ANP infusion of UV, FENa and CH2O were far less dramatic. The response of UV, UNaV and FENa in cirrhotics with mild ascites was delayed compared to cirrhotics without ascites. These results suggest that the blunted natriuretic responsiveness to ANP is contributory to the pathogenesis of initial sodium retention in cirrhotics.

Our experience showed that we can streamline the management of patients with upper GI bleeding with joint efforts by physicians and surgeons. Secondly, endoscopic epinephrine injection treatment is an effective hemostatic technique to control active ulcer bleeding.

The role of endogenous platelet-activating factor (PAF) in the control of pancreatic blood flow during caerulein stimulation was investigated. Pancreatic blood flow in anesthetized rats was measured continuously by laser Doppler flowmetry for 2h during the intravenous infusion of caerulein (0.25 μg/kg per h). Pancreatic blood flow showed a gradual, consistent, and significant increase, reaching 114.2±2.3% of the basal value after 120 min. Changes in pancreatic blood flow induced by caerulein were completely inhibited by a cholecystokinin (CCK) antagonist (loxiglumide, 5 mg/kg per h, i.v.) and by a specific PAF antagonist (CV-6209, 1 mg/kg, i.v.-bolus). Systemic blood pressure remained stable in all groups. These results suggest an important role of endogenously yielded PAF in regulating pancreatic blood flow during caerulein stimulation to the pancreas.

The main cause of azathioprine (AZA)/6-mercaptopurine (6MP)-induced adverse reactions is a reduction in the activities of the metabolizing enzymes thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphohydrolase (ITPA). Adverse reactions develop at a high frequency in Japanese patients at half the dose required for European and American patients; however, the association with TPMT and ITPA gene polymorphisms in Japanese has not been fully investigated. Gene mutations of TPMT and ITPA, the major AZA/6-MP -metabolizing enzymes, were investigated retrospectively in 16 Japanese patients with inflammatory bowel disease (IBD) in whom AZA/6MP treatment induced adverse reactions. The TPMT gene was found to have a wild-type sequence in all patients, but in the ITPA gene a mutation, 94C>A, was detected at a rate of 50% (8/16), with 83.3% (5/6) occurring in patients with acute bone marrow suppression and 75% (3/4) in those with agranulocytosis. The 94C>A allele frequency was 10 of 32 (0.313; 95% CI, 0.180–0.486). Adverse reactions developed earlier in patients with the 94C>A mutation. However, in half the patients, no gene polymorphism was noted. It is suggested that the ITPA gene mutation is closely related to the adverse reactions of AZA/6-MP in Japanese patients, and screening for the mutant allele is useful for predicting the most serious adverse reactions, agranulocytosis and acute bone marrow suppression.