Area postrema lesion alters the effects of peptide YY on 2-DG-stimulated pancreatic exocrine secretion.

Previously we demonstrated that circulating peptide YY (PYY), which inhibits pancreatic exocrine secretion, binds to specific receptors in the area postrema (AP); therefore we have tested the hypothesis that the removal of the AP (APX) will alter the effects of PYY on pancreatic secretion in awake rats. One-month after AP lesion or sham lesion, rats were implanted with pancreatic, biliary, duodenal, and intravenous catheters. After recovery from the surgery, unanesthetized rats were infused with vehicle or PYY (30 pmol/kg/hr or 100 pmol/kg/hr) under basal or 2-deoxy-D-glucose (2-DG) stimulated (75 mg/kg, intravenous bolus) conditions. PYY at 30 pmol/kg/hr inhibited basal pancreatic fluid secretion in sham-operated rats, but not APX rats. PYY at 100 pmol/kg/hr stimulated basal pancreatic protein secretion in sham-operated rats, and this effect was also lost in APX rats. PYY at 30 and 100 pmol/kg/hr inhibited peak 2-DG stimulated protein secretion to a greater extent in APX rats as compared to sham-operated rats (P < 0.05). Since PYY inhibition of basal pancreatic secretion is AP dependent and inhibition of 2-DG stimulated pancreatic secretion is AP independent, we conclude that the 2-DG pathway of pancreatic secretion differs from the pathway responsible for basal secretion, and that APX potentiates the inhibitory effect of PYY on the 2-DG pathway.

PYY inhibits CCK-stimulated pancreatic secretion through the area postrema in unanesthetized rats.

Peptide YY (PYY) inhibits CCK-8-secretin-stimulated pancreatic secretion in vivo. To investigate whether CCK-8-secretin-stimulated pancreatic secretion is mediated through a vago-vagal pathway and whether PYY inhibits this pathway through the area postrema (AP), chronic pancreatic, biliary, and duodenal catheters were implanted in AP-lesioned (APX) or sham-operated rats. The effects of APX on pancreatic secretion stimulated by bethanechol, pancreatic juice diversion (PJD), or CCK-8-secretin, were tested, with and without background PYY infusion, in unanesthetized rats. APX reduced basal pancreatic secretion by 15-20% (P < 0.01). APX had no effect on bethanechol-stimulated secretion and potentiated protein secretion stimulated by PJD (396 vs. 284%) and exogenous CCK-8-secretin. In sham-operated rats, background PYY potently inhibited CCK-8-secretin-stimulated pancreatic fluid (1.8 vs. 48.2%) and protein secretion (3.7 vs. 45.8%) but potentiated fluid (52.9 vs. 43.1%) and protein (132.9 vs. 68.9%) secretion in APX rats. Our findings demonstrate that PYY inhibits CCK-8-secretin-stimulated pancreatic secretion through an AP-dependent mechanism in sham-operated rats. The AP also contributes to basal pancreatic secretion.

PYY potently inhibits pancreatic exocrine secretion mediated through CCK-secretin-stimulated pathways but not 2-DG-stimulated pathways in awake rats.

Peptide YY (PYY) is an important modulator of stimulated pancreatic exocrine secretion. PYY acts proximal to the acinar cell but the exact site and mechanism of action are unknown. The aim of the present study is to determine the pathway through which PYY exerts its effect on the exocrine pancreas in awake rats under physiological condition. When pancreatic secretion was stimulated by graded doses of cholecystokinin (CCK) (14, 28, 58 pmol/kg/hr) with secretin (1.25, 2.5, 5.0 pmol/kg/hr) or CCK alone at 28 pmol/kg/hr, PYY1-36 dose-dependently inhibited pancreatic secretory responses. Moreover, PYY1-36 at 50 pmol/kg/hr almost completely blocked the stimulation by CCK (P < 0.01). Although background infusion of PYY1-36 or PYY3-36 at 12.5 pmol/kg/hr inhibited basal pancreatic fluid and protein secretion, but both of them only partly inhibited the subsequent 2-DG stimulated pancreatic fluid and protein secretion. Furthermore, PYY1-36 at 50 pmol/kg/hr failed to inhibit 2-DG-stimulated pancreatic secretion. These results confirm that PYY1-36 inhibits CCK-stimulated pancreatic secretion under all experimental conditions. However, in the awake, surgically recovered rat, PYY1-36 at both low and high doses failed to fully inhibit 2-DG-stimulated pancreatic secretion. Therefore, the site of PYY's inhibitory action on pancreatic secretion appears to be primarily on the CCK-stimulated pathway at a site proximal to the convergence of the CCK and 2-DG pathways.

PYY regulates pancreatic exocrine secretion through multiple receptors in the awake rat.

Peptide YY (PYY) is one of several regulatory peptides reported to modulate pancreatic secretion. PYY circulates in two forms, PYY1-36 and PYY3-36, and binds to multiple receptor subtypes. We sought to determine if PYY1-36 or PYY3-36 regulates neurally mediated pancreatic secretion through the Y1, Y2, and/or Y5 receptor subtypes. Experiments were conducted in awake, surgically recovered rats. In order to determine the effects of the PYYs on basal pancreatic secretion, either PYY1-36, [Pro34] PYY1-36 (a Y1/Y5 agonist), or PYY3-36 (a Y2/Y5 agonist) were infused for 40 min at doses of 0, 12.5, 25, or 50 pmol/kg/hr while measuring pancreatic juice volume and protein. PYY1-36 increased pancreatic protein secretion at 25 and 50 pmol/kg/hr (P < 0.05) in a dose-dependent manner (P < 0.001, R2 = 0.990). The Y2/Y5 receptor agonist PYY3-36 significantly inhibited pancreatic juice volume and protein at 12.5 and 25 pmol/kg/hr, but stimulated protein secretion at higher doses (P < 0.001, R2 = 0.995). The Y1/Y5 agonist, [Pro34] PYY1-36, had no significant effect on basal pancreatic exocrine secretion. Therefore, PYY1-36, PYY3-36 and [Pro34] PYY1-36 produced different, dose-dependent changes on basal pancreatic exocrine secretion. Inhibition of pancreatic secretion by circulating PYY1-36 and PYY3-36 are primarily mediated by the Y2 receptor. Since [Pro34] PYY1-36 did not change pancreatic secretion, it can be concluded that circulating PYY1-36 or PYY3-36 does not modulate pancreatic secretion through the Y1 or Y5 receptors. Since the stimulatory effects of PYY1-36 on pancreatic secretion could not be explained by the actions of PYY3-36 or [Pro34] PYY1-36 on Y1 or Y2 receptors, and since PYY1-36 fails to bind to Y3 or Y4 receptors, we also conclude that PYY1-36 may stimulate pancreatic secretion in a dose-dependent mechanism through a PYY receptor subtype different from Y1, Y2, Y3, Y4 or Y5.

[Gallbladder emptying evaluation in chronic calcifying pancreatitis, by means of a scintilographic study with Tc-99m DISIDA]. / Avaliação do esvaziamento da vesícula biliar em portadores de pancreatite crônica calcificante, através do estudo cintilográfico com Tc-99m DISIDA.

The aim of this study was to analyze the gallbladder motor function in chronic pancreatitis (CP) patients. Gallbladder emptying was evaluated in 11 patients, without and with addition of pancreatic extract and in ten controls. The results were compared and analyzed statistically. The ejection fraction (EF) of the gallbladder (GB) at 30, 45 and 60 minutes were calculated by using Tc-99m DISIDA scintigraphy. The EF of GB at 60 minutes was significantly higher in the controls when compared to patients, although the results between patients were similar without and with addition of pancreatic extract. The results suggest that the delay in the GB emptying does not depend on the eventual alteration in the intestinal phase of the vesicular stimulation, but it probably results from a mechanic factor, which depends on the chronic pathological process located in the head of the pancreas.

[Complications of chronic pancreatitis in São Paulo (Brazil)]. / Complicações das pancreatites crônicas em São Paulo.

Chronic Pancreatitis (CP) presents distinctive characteristics in different geographical areas. With the purpose of evaluating the clinical characteristics, particularly in relation to the frequency and etiopathogeny of the complications in São Paulo, in comparison to other centers, 545 patients with this disease were analyzed, retrospectively, 493 (90.5%) of these patients were males and 52 (9.5%) females, with ages ranging from 8 to 88 (38.2 +/- 9.3 years). The diagnosis of CP was based on criteria previously adopted by the Pancreas Group of Gastroenterology Studies of the Medical School of São Paulo. The principal etiologic factors were represented by: chronic alcoholism in 509 of the 545 patients (93.4%), hereditary factors in four (0.7%), malnutrition in three (0.5%), metabolic alterations in three (0.5%) and obstruction to the pancreatic flow in two patients (0.3%). In 24 (4.4%) of the 545 patients, the etiologic factor could not be established, due to the idiopathic nature of the disease. Of the 509/545 patients (93.4%) presenting chronic ethylism, alcoholic consumption was characterized by: a) mean age alcoholic consumption was initiated: 19.5 +/- 6.5 years; b) mean daily alcoholic consumption in grams of pure ethanol: 358.6 +/- 282.0 g/d; c) mean time of alcoholic consumption: 19.8 +/- 8.8 years, and d) mean age of the appearance of clinical symptoms: 34.9 +/- 9.8 years. The clinical complications were always investigated in accordance with the pre-established protocol; the principal complications observed were represented by: gastrointestinal compression (3.3%), jaundice (24%), cysts (35.9%), cavity effusions (13.3%), pancreatic necrosis (4.7%), abscesses (3.6%), digestive hemorrhage of pancreatic origin (2.3%) and fistulae (1.1%). The incidence of these complications, particularly cysts, cavity effusions and pancreatic necrosis, was greater in the patients studied than in those observed in other regions, probably due to the presence of more intense and frequent anatomopathologic lesions found in these patients, possibly resulting from the greater consumption of alcohol compared to patients with this disease in other centers. The etiopathogenic mechanisms for the complications were individually analyzed and interpreted.

Secretory, endoscopic and histopathologic changes and prevalence of Helicobacter pylori in the gastroduodenal mucosa in patients with chronic alcoholic pancreatitis.

Aiming at establishing the prevalence of peptic ulcer in chronic alcoholic pancreatitis and an eventual correlation with gastric acid secretion and endoscopic and histopathologic alterations as well as the presence of Helicobacter pylori in the gastroduodenal mucosa, thirty patients with chronic alcoholic pancreatitis (Group I) and ten control subjects (Group II) were prospectively studied. After upper gastrointestinal endoscopy was performed. Group I was subdivided according to the lack (Subgroup Ia) or a presence (Subgroup Ib) of peptic ulcer. The prevalence of peptic ulcer in these patients was 23.33% clearly higher than that reported in the general population. Baseline and stimulated acid secretion as well as baseline gastrinemia among the subgroups and groups were similar. There was no statistically significant difference in the other parameters evaluated. Due to the increased prevalence of asymptomatic peptic ulcer in patients with chronic alcoholic pancreatitis. Upper gastrointestinal endoscopy is suggested as a diagnosis routine and follow-up of this group of patients.

Changes in capillary permeability during severe experimental acute pancreatitis in rats.

Abnormalities of microcirculation are thought to have an important role in the pathogenesis of severe acute pancreatitis (SAP) and in the associated multiple organic failure. We studied changes in capillary permeability during experimental SAP in rats. Necrotizing acute pancreatitis was induced by retrograde injection of sodium taurocholate in pancreatic ducts in rats (n = 30). The animals were distributed in three groups in which the spaces of compartmental distribution as well as the tissue distribution of labeled tracers were evaluated with the use of erythrocytes and albumin tagged with radioactive chromium, apart from determining the volume of total body water. All the studies were carried out four hours after the induction of acute pancreatitis and the administration of radioactive tracers.

Primary extranodal non-Hodgkin lymphoma of the extrahepatic bile duct mimmicking Klatskin tumor.

This report describes one case of primary non-Hodgkin lymphoma of the extrahepatic biliary tree. The main symptom was obstructive jaundice. Cholangiography demonstrated stricture of the bile duct which resembled the appearance of cholangiocarcinoma. The surgical approach allowed complete ressection. The histopathological analyses showed a centrocitic-centroblastic follicular non-Hodgkin lymphoma. She underwent chemotherapy, developed severe bone marrow hypoplasia, but 48 months after surgery, the patient is doing well.

[Cavity effusions in patients with chronic pancreatitis]. / Derrames cavitários em portadores de pancreatite crônica.

In Brazil, the incidence of IPF due to alcohol-induced CP seems to be higher than in other countries. The authors analysed some general, epidemiologic, laboratory and radiologic features in 98 patients with CP, all of them alcoholics, divided in two groups: 49 patients without IPF (I) and 49 patients with IPF (II). The authors first analysed the following parameters in each group and then comparatively in both groups: age, sex, race, smokers and daily consumption of cigarettes, daily consumption of alcoholic beverages, years of alcohol consumption, and mortality. The authors concluded that pancreatic fistula plays in effusions the main role, secondary to cysts disruption or necrosis of the main pancreatic duct.

Epidemiology and etiology of chronic pancreatitis in Brazil: a tale of two cities.

We observed 797 consecutive cases of chronic pancreatitis from 1963 to 1987 in the cities of Belo Horizonte and São Paulo. Alcoholism was the main etiological agent, responsible for 714 cases (89.6%). Chronic calcifying pancreatitis from different etiologies, alcohol, idiopathic, nutritional, and familial, was the most important form of chronic pancreatitis, with 786 cases (98.6%). Only three cases of chronic obstructive pancreatitis were diagnosed. Eight cases of chronic pancreatitis, anatomicopathologically studied, have not showed the typical pancreatic changes of either chronic calcifying pancreatitis or of obstructive pancreatitis and were impossible to classify according to the 1984 Marseilles' classification.

[Chronic pancreatitis: clinical characteristics, complications and association with other diseases]. / Pancreatites crônicas: características clínicas, complicações e associação com outras afecções.

The clinical aspects, complications and association with other diseases were investigated in 407 patients with chronic pancreatitis. The most frequent symptoms were abdominal pain (93.6%), weight loss (91.6%), diabetes (37.8%) and malabsorption (31.7%). Pancreatic cysts (32.6%), ascites and/or pleural effusion (12.5%), pancreatic necrosis (11.2%), gastrointestinal bleeding (12.8%) and pancreatic abscess (7.3%) were the most frequent complications. The symptoms and complications observed are discussed and their incidences compared to those reported from other countries.

[Spontaneous remission of pancreatic cysts in patients with chronic pancreatitis]. / Regressão espontânea de cistos pancreáticos em portadores de pancreatite crônica.

Thirty one alcoholic patients with pancreatic cysts were studied by ultrasonographic scanning with the purpose to observe the evolution of the cysts. The mean time of the follow-up was 15.6 +/- 9.2 months; the patients were aged 40.2 +/- 9.3 years (male = 93.5%; female = 6.4%) the average pure ethanol intake was 288.3 +/- 185.9 ml for a period of 20.8 +/- 9.3 years. In 21 of the 31 patients (67.7%) the ultrasonographic examination showed total spontaneous resolution of the cysts within a time span of less than 18 months. The majority of the parameters studied (age, time and volume of ethanol intake, pain, diabetes, calcifications and previous cyst drainage) had no relation with the evolution of the cysts. In 11 patients (52.3%) the cysts showed an initial enlargement before decreasing in size. The cysts located in the pancreatic head showed less tendency to spontaneous resolution. Complications were observed in two patients: intra-cystic haemorrhage in one and rupture into the peritoneal cavity in the other. Our observations suggest that patients with pancreatic cysts secondary to chronic alcoholic pancreatitis should be controlled with periodical ultrasonography. Surgical approach should be reserved for patients with complications.

[Etiology of chronic pancreatitis in São Paulo: a study of 407 cases]. / Etiologia das pancreatites crônicas em São Paulo: estudo de 407 casos.

The etiology of chronic pancreatitis was investigated in 407 patients: 381 (93.6%) had a history of heavy alcoholic ingestion (average = 295.3 +/- 171.3 g of ethanol) during a time of 19.2 +/- 8.0 years: five patients (1.0%) had familial background of pancreatitis, two (0.5%) had the obstructive form, and two (0.5%) presented history of malnutrition. In 18 patients (4.4%) it was not possible to determine the etiology. Patients with the alcoholic form started the alcohol abuse at the age of 19.4 +/- 6.0 years. A careful dietetic inquiry showed that patients with chronic pancreatitis lived on a diet which was significantly richer in protein than that of patients of the control group (p less than 0.01). Attention is called to the high incidence of chronic alcohol abuse in patients with chronic pancreatitis.

[Gastro-entero-pancreatic hormones in patients with chronic Chagas' disease]. / Hormônios gastro-êntero-pancreáticos em portadores de doença de Chagas crônica.

The seric levels of gastrin, pancreatic glucagon, pancreatic polypeptide, enteroglucagon, motilin and cholecistokinin were evaluated in ten patients with chronic Chagas' disease and compared with those observed in nine normal control subjects. The seric values of all the hormones were determined on basal stimulation, after continuous intravenous secretin infusion and infusion of stepwise increased concentrations of caerulein (direct stimulation), and after intravenous secretin administration followed by intraduodenal instilation of increased concentrations of phenylalanina (combined stimulation). All the hormones, basal and after direct stimulation, showed similar values, except gastrin that in the chagasic group presented higher levels than in control subjects. Phenylalanine and pancreatic polypeptide showed significantly higher values in the control group than in the one of patients with Chagas' disease. The hormonal response in patients with chronic Chagas' disease suggested a neural impairment of the enteropancreatic axis.

[Splenic vein thrombosis as cause of digestive hemorrhage: ruptured esophageal varices or hemorrhagic gastritis secondary to portal hypertension?]. / Trombose da veia esplênica como causa de hemorragia digestiva: varizes gástricas rotas ou gastrite hemorrágica secundária à hipertensão portal?

The clinical evolution and treatment of two patients with alcoholic chronic pancreatitis complicated with digestive hemorrhage localized in the gastric corpus and fundus are discussed. The clinical picture and the endoscopic features suggested that the hemorrhage was due to hemorrhagic gastritis and not to rupture of varicose veins. Hemorrhagic gastritis as a consequence of segmentary portal hypertension may be responsible for the difficulty in establishing the etiology of digestive hemorrhage in such cases.