Effect of pancreastatin on cerulein-stimulated pancreatic blood flow and exocrine secretion in anaesthetized rats.

BACKGROUND: Pancreastatin (PST) is an inhibitor of pancreatic exocrine secretion in vivo but not in vitro, which suggests that the inhibitory effect of PST is indirect, that is, not mediated by a specific receptor on pancreatic acinar cells. In this study, we investigated the effects of PST on pancreatic exocrine secretion and local pancreatic blood flow in anaesthetized rats to elucidate the participation of PST in indirect regulation of pancreatic exocrine function through blood supply. METHODS: Pancreastatin (100, 200 or 500 pmol/kg per h) was administered intravenously under background infusion of cerulein (0.5 microg/kg per h), a cholecystokinin analogue. Pancreatic exocrine secretion was monitored by volume and protein output of the pancreatic juice and local pancreatic blood flow was measured by the hydrogen gas clearance method. RESULTS: Pancreastatin significantly reduced cerulein-induced local pancreatic blood flow in a dose-dependent manner. Pancreatic exocrine secretion was also reduced significantly by PST dose-dependently. Pancreastatin did not change systemic blood pressure. These results suggested that the reduction of pancreatic blood flow is associated with the reduction of pancreatic exocrine secretion. CONCLUSIONS: We conclude that the mechanism of PST-induced inhibition of pancreatic exocrine secretion is, at least, partly mediated by the reduction of local pancreatic blood flow through blockade, caused by the action of cerulein on pancreatic blood flow.

A case of successfully treated giardiasis in pancreas.

We report a case of giardiasis in the pancreas in a patient with diabetes mellitus. The patient is interesting in the following: 1) Giardia lamblia was found only in the pancreas and not in the gall bladder by cytology on endoscopic retrograde cholangiopancreaticography (ERCP) and by cerulein-secretin test (CST). 2) ERCP revealed multiple small cysts scattered throughout the pancreas. 3) Decreased pancreatic exocrine function was recovered by treatment with metronidazole.

Autoimmune pancreatitis as a new clinical entity. Three cases of autoimmune pancreatitis with effective steroid therapy.

The most common forms of chronic pancreatitis are related to alcohol ingestion, whereas the entity of non-alcohol-associated (idiopathic) pancreatitis is poorly understood. Autoimmunity has been suggested as a possible etiologic factor of idiopathic chronic pancreatitis. A total of 362 Japanese patients underwent endoscopic retrograde pancreatography (ERP) for suspected pancreatic disease, and 161 were diagnosed with chronic pancreatitis. Among them, we found three cases (1.86% incidence) of unique chronic pancreatitis, in which ERP revealed diffuse narrowing of the main pancreatic duct with an irregular wall. We diagnosed these three patients as having pancreatitis associated with an autoimmune mechanism morphologically and biochemically and started them on steroid therapy. The characteristics of the these three patients were as follows: hypergammaglobulinemia, eosinophilia, ultrasonography showing hypoehoic diffuse swelling in the pancreas (sausage-like appearance), ERP showing diffuse narrowing of the main pancreatic duct with irregular like thumbprint-like marks, reversible exocrine insufficiency, and positive anti-carbonic anhydrase II antibody. After one month of the treatment with steroids, pancreatitis dramatically improved morphologically and enzymatically. Here we describe these cases of the suspected autoimmune chronic pancreatitis. We must recognize the concept and the features of autoimmune pancreatitis in order to avoid unnecessary surgery as pancreatic cancer.

Acinar-islet cell carcinoma presenting as insulinoma.

A case of acinar-islet cell carcinoma presenting as insulinoma is reported. The patient was a 28-year-old man who presented with two convulsive episodes. Fajans' index [immunoreactive insulin (IRI; microU/ml/ glucose mg/dl)] and Turner's [IRI (microU/ml) x 100/glucose (mg/dl) - 30] index were high (2.8 and 308, respectively), as were serum proinsulin levels (550 pg/ml). Abdominal computed tomography and angiography revealed a highly vascular tumor in the pancreatic tail and several similar tumors in the liver. Histologic features of a biopsy specimen from a hepatic tumor were those of a malignant pancreatic endocrine tumor. Insulin secretion by the liver metastases was confirmed by venous sampling after arterial stimulation with calcium. These findings led us to diagnose malignant insulinoma with liver metastases. Serum levels of alpha-fetoprotein and trypsin were markedly elevated, to 2234 ng/ml (normal < 10) and 22,000 ng/ml (normal < 460) respectively, and these levels continued to rise with further growth of the liver metastases. Immunohistochemically, the metastatic liver tumor specimen was positive for alpha-fetoprotein, alpha 1-antichymotrypsin, chromogranin A, and neuron-specific enolase. These findings of amphicrine features in the tumor were indicative of acinar-islet cell carcinoma that produced alpha-fetoprotein and trypsin in addition to insulin.

[Standardization of serum lipid examination: an attempt in Oita].

There is an obvious difference in currently available clinical laboratory data between hospitals. With the advent of information systems, the clinical laboratory information in the future must be standardized so that it can be used in medical treatment and health control throughout the life patients time. Establishing publicly acknowledged standards is essential for standardization to be translated into practice. The standards for clinical laboratory examination in Japan are approved by consensus in the Japanese Committee for Clinical Laboratory Standards (JCCLS). However, standards have yet to be established for most laboratory examinations. This poses is a major obstacle in promoting the standardization. Standardization should be implemented carefully with consideration of the worldwide trend. That is probably the reason why the consultation and approval at JCCLS have been delayed, but it is hoped that standards will be established as soon as possible. The committee for quality control survey in Oita Medical Association organized a Lipid Unit of the Sectional Committee for Standardization in 1994 and has since implemented standardization according to the lipid standardization program of the U.S. Centers for Disease Control and Prevention (CDC) with some modifications. Measures for improvement have been adopted for a trial period in parallel with four surveys, and in September, 1995 all 9 hospitals passed the standardization test performed on the basis of the CDC provisions for certification. The Oita Medical Association plans to expand the lipid standardization to all parts of the prefecture using the trial of standardization by the Lipid Unit as a model.

Measurement of pancreatic blood flow with the intraductal electrode method of the hydrogen clearance technique in acute pancreatitis in rats.

Measurement of local pancreatic blood flow during acute pancreatitis is thought of as being technically difficult in smaller animals. In this study, we first employed an intraductal electrode method of the hydrogen clearance technique for measurement of changes in local pancreatic blood flow in two types of acute pancreatitis in rats, then compared this method with an interstitial electrode method that has been used in rats. There was a very close correlation between these methods (r = 0.998, p < 0.001). The intraductal electrode method was easily performed and caused minimal tissue damage.

Case report: mucin-producing cystic neoplasm of the pancreas with onset in childhood.

Mucin-producing tumours of the pancreas have been recently reported with increasing frequency and most cases have occurred in middle-aged and elderly people. In the present report, a case of a 21-year-old man with mucinous cystadenoma of the pancreas is reported. He had a long history of recurrent pancreatitis from the age of 8. When he was aged 10, the first branch of the main pancreatic duct was shown to be enlarged on endoscopic retrograde pancreaticography (ERP). A series of ERP studies and computed tomography scans performed over a period of 11 years demonstrated continuing growth of this enlargement of the pancreatic duct. Pancreaticoduodenectomy was performed and the patient has been well without further episodes of acute pancreatitis and has been free of recurrent tumour for 1 year.

Simultaneous determinations of pancreatic phospholipase A2 and prophospholipase A2 in various pancreatic diseases.

Pancreatic phospholipase A2 (PLA2) is secreted into the pancreatic juice by pancreatic acinar cells as a proenzyme (proPLA2), which is activated by trypsin. Radioimmunoassays with monoclonal antibodies to PLA2 and proPLA2 were used to examine the serum PLA2 and proPLA2 levels simultaneously in patients with various pancreatic diseases. In healthy subjects, proPLA2 proved to be the major form of the enzyme. The serum PLA2 level were found to be significantly increased in patients with acute pancreatitis, the active phase of chronic relapsing pancreatitis, and the early stage of pancreatic cancer. In the terminal stage of pancreatic cancer the serum PLA2 level became low. In patients with chronic pancreatitis, significant correlations were observed between the levels of factors evaluated by the secretin test and the serum total PLA2 and proPLA2 level, but not the PLA2 level. The serum PLA2 and proPLA2 concentrations, and the proportion of proPLA2 in the total, were within normal ranges in patients with liver cirrhosis, hepatocellular carcinoma, and chronic renal failure. These results suggest that simultaneous measurements of serum PLA2 and proPLA2 are clinically useful for diagnosis and monitoring of the active phase of pancreatitis.

In vivo activity on murine tumors of a novel antitumor compound, N-beta-dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]phenazine-6-carboxamide sodium salt (NC-190).

A novel antitumor compound, N-beta-dimethyl-aminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190) was evaluated for its antitumor activity in experimental murine tumor systems. In the initial studies with P388 leukemia (i.p.-i.p.), NC-190 led to an increase of greater than 200% in life span (ILS), and 75% of the mice were alive on day 30, when the optimal dose (50 mg/kg, days 1-5) was given. Additionally, the compound had significant activities against i.p. inoculated mouse L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma, sarcoma 180, mouse hepatoma MH134, and rat Yoshida sarcoma and Yoshida ascites hepatoma AH130. The optimal dose resulted in a greater than 280% ILS with a 30-day survival of 50% in mice with L1210 leukemia (100 mg/kg, days 1-5), a 156% ILS in mice with B16 melanoma (50 mg/kg, days 1-5), a 98% ILS with a 90-day survival of 25% in mice with M5076 reticulum cell sarcoma (25 mg/kg, days 1, 5, 9, and 13), a greater than 300% ILS with a 60-day survival of 50% in mice with sarcoma 180 (50 mg/kg, days 3-10), a 148% ILS with a 60-day survival of 25% in mice with MH134 (25 mg/kg, days 1-5), a 129% ILS with a 60-day survival of 12.5% in rats with Yoshida sarcoma (12.5 mg/kg, day 3-10), and a greater than 161% ILS with a 60-day survival of 50% in rats with AH130 (6.3 mg/kg, days 3-10). In the experiments with s.c. inoculated tumors, NC-190 not only inhibited tumor growth, but also increased the life span of mice with Lewis lung carcinoma or B16 melanoma. The 60-day survivors accounted for 60% and 30% in mice with Lewis lung carcinoma and B16 melanoma, respectively. The compound significantly inhibited the spontaneous lung metastasis of Lewis lung carcinoma by more than 90% when eight daily i.v. injections were given. NC-190 was active by the i.p., s.c., and i.v. routes. Five consecutive daily i.p. doses (days 1-5) were more effective than a single dose (day 1), two doses (days 1 and 5), or three doses (days 1, 5, and 9). NC-190 warrants further study as a potential antineoplastic agent against human neoplasms, as it has a broad spectrum of antitumor activity and inhibits metastasis.