The influence of benazepril and amlodipine on the expression of secretin and somatostatin in spontaneously hypertensive rats / 中国应用生理学杂志

OBJECTIVES@#Investigate the influence of benazepril and amlodipine on the expression of secretin (PZ) and somatostatin (SS) in spontaneously hypertensive rats (SHR).@*METHODS@#Forty-five SHRs (14 weeks old, male) were randomly assigned into 3 groups (=15):SHR group, Benazepril group (which was given benazepril 0.90 mg·kg·d) and Amlodipine group (SHRs were given amlodipine 0.45 mg· kg·d), taking WistarKyoto(WKY) as normal control (=15), meanwhile, rats in SHR group and WKY group were given the same volume of distilled water. After 8 weeks of intervention, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was detected by enzyme-linked immunoassay and RT-PCR.@*RESULTS@#After 8 weeks of intervention, compared with the WKY group, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was increased significantly in SHR group (<0. 05). Compared with SHR group, the expression of PZ in duodenum and SS in sinuses ventriculi was decreased significantly in Benazepril group and Amlodipine group (<0.05). Compared with Benazepril group, in Amlodipine group the expression of PZ mRNA in duodenum and SS mRNA in sinuses ventriculi was decreased more significantly (<0.05).@*CONCLUSIONS@#The regulation disorder of PZ in duodenum and SS in sinuses ventriculi exists in SHR. The antihypertensive effect of benazepril and amlodipine may be realized by regulating the expression of PZ and SS, while the regulation of amlodipine is more obvious than benazepril.

Evaluation of Asymptomatic Hyperamylasemia and Hyperlipasemia / 대한췌담도학회지

There are increasing number of cases of serum amylase and lipase levels being examined as part of health screening, but the clinical significance of these amylase and lipase levels is unclear. When the clinicians encounter patients with elevated pancreatic enzymes, the most common causes such as acute pancreatitis, hepatic or renal dysfunction should be ruled out first by thorough history taking, physical examination, and laboratory tests. Further tests including abdominal ultrasonography or computed tomography, lipid profile, tumor marker, isoenzyme, and calculation of amylase-to-creatinine clearance ratio or polyethylene glycol precipitation test should be performed to exclude other causes. If the pancreatic enzymes are continuously elevated through repeated tests without any apparent etiology, the diagnosis is made with chronic non-pathological pancreatic hyperenzymemia (CNPH). Magnetic resonance cholangiopancreatography is very useful and important modality for the patients with CNPH but the clinical significance of magnetic resonance cholangiopancreatography with secretin stimulation is still unclear. They can be evaluated through endoscopic ultrasonography with preference but it is less suitable for follow-up. Individualized approaches should be made after considering the need for active treatment or periodic follow-up for the benign pancreatic diseases associated with CNPH. It is difficult to conclude until more long-term data are reported because there are only limited number of researches and consensus on the range of tests to be performed for diagnosis, clinical significance of benign findings and end of follow-up in patients with CNPH.

Effect of secretin on the expression of cPLAand mPGEs-1 in mouse endometrial stromal cell during early pregnancy / 生理学报

Secretin, a gastrointestinal peptide, has been found to be expressed in mouse endometrial stromal cells (mESCs) during early pregnancy. In order to further investigate the function of secretin during embryo implantation, the expression levels of secretin, secretin receptor, cytosolic phospholipase A(cPLA) and membrane prostaglandin E synthase 1 (mPGEs-1) were detected in the mice uterus from day 4 to 8 of pregnancy by real-time PCR, ELISA and in situ hybridization. mESCs isolated and cultured from day 4 of pregnancy were transfected with secretin expression vectors or treated with H89, a PKA inhibitor. Then the expression levels of cPLA, mPGEs-1 and cAMP responsive element-binding protein (CREB) were detected by real-time PCR and Western blot. The concentration of prostaglandin E2 (PGE) in the supernatant was determined by ELISA. The result showed that secretin, cPLAand mPGEs-1 mRNA expression increased gradually in implantation sites from day 5 to day 7 of pregnancy with the same tendency. The secretin levels in serum were significantly higher on days 6, 7 and 8 of pregnancy than that on day 5 of pregnancy. The concentration of secretin was significantly higher in implantation sites on days 6, 7 than that in non-implantation site on day 5. Transfection of secretin expression vector promoted cPLA, p-cPLAand mPGEs-1 expressions in mESCs, but not PGElevel in the supernatant. H89 could effectively inhibit the expression of CREB, p-CREB, p-cPLAand cPLAinduced by secretin. The results showed that the increased secretin expression in mESCs during embryo implantation may promote p-cPLA, cPLAand mPGEs-1 expression, and the promotion may be through PKA signaling pathway.

Ultrasonido endoscópico en patologías del páncreas / Endoscopic ultrasound in pancreatic diseases

El ultrasonido endoscópico (EUS) ha revolucionado el diagnóstico y el manejo de muchas patologías de la vía digestiva, particularmente la patología pancreática, convirtiéndose en un examen prácticamente imprescindible en el abordaje diagnóstico y terapéutico de un paciente con un problema de páncreas. Es necesario dejar en claro que el método no es único y que para lograr una sensibilidad alta y cumplir el objetivo de realizar lo más adecuado, debe sumarse a otros métodos de acuerdo a cada caso, como la ecografía, la tomografía axial computarizada (TAC), la resonancia magnética (MRI) en sus diferentes modalidades, y las pruebas del laboratorio clínico microbiológico y patología. En este artículo se revisarán algunos casos de enfermedades evaluadas con este método, que muestran por qué el EUS, es una herramienta clave para el médico de urgencias y de consulta externa, el internista, el cirujano, el médico del servicio hospitalario y el personal de salud en general, al momento de definir, clasificar y orientar el manejo de determinadas patologías en el tubo digestivo. El EUS es una importante ayuda y no debe ser extraña al personal médico, debe tenerla presente junto a las demás pruebas diagnósticas en patología pancreática. Se señalarán los aspectos más relevantes en cada caso y las indicaciones del EUS.

Endoscopic ultrasound (EUS) has revolutionized the diagnosis and management of many diseases of the digestive tract, particularly the pancreatic ones, becoming a practically essential test in the diagnosis and therapeutic management of a patient with a pancreatic problem. It's necessary to establish the final diagnosis are necesary many tests to achive high sensitivity. It should join with other methods according to each case, such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) in its various forms, and chemical, microbiological and pathology tests. In this article we reviewed some cases of pathologies evaluated by this diagnosis test, which demonstrate why the EUS, is a key for the emergency and outpatient physician, internist, surgeon, doctor of the hospital service and staff health in general, when defining, classifying and guide the management of certain diseases in the digestive tract. The EUS is an important tool and should not be foreign to the medical staff, who must consider it, with other diagnostic tests for pancreatic disease. This article point out the most important aspects in each case and indications of EUS.

Is Oxytocin Application for Autism Spectrum Disorder Evidence-Based?

Autism spectrum disorder (ASD) is characterized by persistent deficits within two core symptom domains: social communication and restricted, repetitive behaviors. Although numerous studies have reported psychopharmacological treatment outcomes for the core symptom domains of ASD, there are not enough studies on fundamental treatments based on the etiological pathology of ASD. Studies on candidate medications related to the pathogenesis of ASD, such as naltrexone and secretin, were conducted, but the results were inconclusive. Oxytocin has been identified as having an important role in maternal behavior and attachment, and it has been recognized as a key factor in the social developmental deficit seen in ASD. Genetic studies have also identified associations between ASD and the oxytocin pathway. As ASD has its onset in infancy, parents are willing to try even experimental or unapproved treatments in an effort to avoid missing the critical period for diagnosis and treatment, which can place their child in an irreversible state. While therapeutic application of oxytocin for ASD is in its early stages, we have concluded that oxytocin would be a promising therapeutic substance via a thorough literature review focusing on the following: the relationship between oxytocin and sociality; single nucleotide polymorphisms as a biological marker of ASD; and validity verification of oxytocin treatment in humans. We also reviewed materials related to the mechanism of oxytocin action that may support its potential application in treating ASD.

Advanced Pharmacotherapy Evidenced by Pathogenesis of Autism Spectrum Disorder

In clinical practice, pharmacological treatment is mostly focused on behavioral symptoms in everyday life. Nevertheless, persistent effort continues to develop medication for causal treatment. Recent changes in diagnostic criteria from Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) to DSM-5 would affect not only diagnosing approaches, but also therapeutic approaches. Because previous pervasive developmental disorders have been integrated into a single entity, the autism spectrum disorder (ASD), we have to prepare for what medications are valuable for the ASD. In this article, we reviewed the following etiological treatment: acetylcholine and glutamate related medicine; amino acid medicine such as secretin, endogenous opioid, and oxytocin; complementary and alternative medicine such as chelating agents, vitamins, and omega-3; promising drugs related to the scope of pharmacogenetics currently under study.

Streptozotocin-induced diabetes, bile-pancreatic secretion and insulo-pancreon-axis interaction / Streptozotocin-induced diabetes, bile-pancreatic secretion and insulo-pancreon-axis interaction.

The present tests were undertaken in order to analyze in male Wistar rats the changes in the exocrine and endocrine pancreas and on the interactions that normally evolve in the insulo-pancreon-axis. To evaluate this by a single i.p. Boots secretin injection, glycemia (G), amylasemia (A) and lipasemia (L) were determined. In bile-pancreatic secretion, we analyzed, pre and post-secretin, the following parameters: volume (V), bicarbonate output (BO), amylase output (AO) and lipase output (LO). Three groups of tests were done: a) control (C); b) streptozotocin-treated non-diabetic-rats (St-ND) and c) streptozotocin-treated diabetic animals (St-D) which showed morning glycemia values higher than 16.0 mmol/l. Four months later, under Tiopental i.p anesthesia, a bile-pancreatic fistula was done. Following a 30 min basal period, Boots secretin (20 CU/kg) was i.p injected. Bile-pancreatic secretion put in evidence a significant fall of BO in both St-ND and St-D series. In controls, AO revealed a post-secretin increase of 160

, while in the St-D rats showed a depression of 41

. The behavior of L was different, being augmented (+27

) in the C, while in the St-D rats the response was significantly higher (+95

). In bile-pancreatic-secretion, the fall of BO and AO in the St-ND and St-D series in respect to the C, are probably consequence of the diminishing potentiating effects exerted normally by insulin on the secretin-induced water and bicarbonate secretion of the pancreon units. In contrast, the rising of LO in the St-D, an expression of an enhancing pancreocyte’s synthesis and secretion of lipase. The blood changes of A (depression) and of L (increase) in respect to the C values, although without reaching significant level, mirror those observed in bile-pancreatic secretion.

Insuficiência exócrina do pâncreas: etiologias / Exocrine pancreatic insufficiency: etiology

Insuficiência exócrina do pâncreas tem sido revisitada em vários compêndios médicos internacionais e suas novas etiologias avaliadas e reconfirmadas. Neste artigo abordamos as causas mais comuns e tradicionais, pancreatite crônica e fibrose cística, bem como as recentemente mais enfatizadas como doença celíaca e diabetes mellitus. Comentamos a clínica e o diagnóstico precoce e o tratamento com reposição enzimática

Pancreatic exocrine insufficiency has been broadly discussed in international medical literature. New aetiologies have been studied and reaffirmed. In this paper we describe common and traditional causes such as chronic pancreatitis and cystic fibrosis as well as the most recently emphasised celiac disease and diabetes. We also review clinical features, early diagnosis and pancreatic enzyme replacement therapy

Gastrin, secretin, GIP and VIP alter levels of IL-2 and IFN-gamma in human peripheral blood mononuclear cells under various culture conditions

Gastrointestinal hormones have traditionally been viewed as mere regulators of gut movement and secretions, but, it is becoming increasingly apparent that other body systems may be affected by these hormones. Secretion of gut hormones is influenced by the type of food we take. Therefore, the more we know about the effects of gut hormones on the various body tissues, the more we know about the different mechanisms by which our diets affect our health. This in vitro study aimed to explore the effects of physiologically-relevant concentrations of four gut hormones on the production of IL-2 and IFN-gamma by human peripheral blood mononuclear cells and how culture conditions may modif_ those effects. Peripheral blood mononuclear cells were separated by density gradient centrifugation from the blood of 15 adults. Cells were cultured with/without PHA and treated with four concentrations of gastrin, secretin, GIP and VIP. IL-2 and IFN-gamma in culture supernatants were assayed by ELISA. Gastrin, secretin, GIP and VIP increased IL-2 and TFN-gamma levels under some culture conditions and depressed lL-2 under other conditions. An increase was oflen observed under culture conditions in which the cytokine production was not initially high. Repeated administration of the hormone was also more likely to result in a stimulatory effect. Physiologically-relevant concentrations of gastrin, secretin, GIP and VIP are potential immunomodulators as they have shown their ability to alter the production of IL-2 and/or IFN-gamma under various culture conditions

Lipasa: una enzima singular por sus interacciones neuro-hormonales. (Revisión y análisis experimental y clínico) / Lipase: a particular enzyme because of its neuro-hormonal interactions

Un objetivo de esta presentación es el de analizar las peculiaridades distintivas de la enzima lipasa proveniente de diferentes fuentes: gástrica (LG), intestinal (LI)hepática (LH), lipoproteica (LLP), pero, en especial, aquella de la pancreática (LP), sobre todo en lo relativo a sus interacciones neuro-hormonales.

Biochemical study on gastrin, secretin and somatostatin homeostasis in end stage renal failure

Chronic renal failure is a complex disease that is associated with enormous biochemical alterations which induce marked multiorgan dysfunctions. Gastrointestinal disorders are diagnosed occasionally while renal failure is not yet recognized. The specific mechanisms underlying these complaints are not yet completely known. Aim: The present study aimed to assess the circulating state of three major biologically active gut hormones i.e. gastrin, secretin and somatostalin. Their responses to standard test meal and to hemodialysis were also determined The present study was conducted on 20 patients with CRFdue to variable kidney diseases. Of them 10 patients receiving conservative treatment only [Conservative group] and the remaining 10 patients undergoing maintenance hemo-dialysis [hemodialysis group] beside the conservative therapy. Also 12 healthy volunteers were similarly investigated. Plasma total gastrin, secretin and somatostatin [S.S] concentrations beside the routine investigations were determined. In conservative uremic group, fasting and one hour postprandial plasma total gastrin, secretin and somatostatin levels were significantly higher than their corresponding normal control levels: Moreover, test meal induced significant increase in these hormones in both CRF and control groups in comparison to their fasting levels. In hemodialysis uremic patients, plasma total gastrin, secretin and somatostatin concentrations before dialysis were significantly higher than their corresponding levels in the normal control and in conservative uremic groups. Hemodialysis caused significant reduction of the circulating gastrin, secretin and somatostatin concentrations when compared with their plasma concentrations before dialysis. However, in hemodialyzed uremics, unlike plasma gastrin and secretin concentrations, plasma SS concentration before dialysis was not significantly different from the fasting level in CRF patients on conservative therapy. Hypersecretinemia and hypersomatostatinemia were concomitant finding with hypergastrinemia in CRF. Disproprotionate synthesis and release of gastrin, secretin and somatostatin can be explained by impairment of the feedback loops and cross regulations in between these hormones. However, being excreted mainly by kidney, impaired excretion of these hormones is also a possible cause of their high circulating concentrations.

The Effect of Secretin on Pepsin Secretion in Heidenhain Pouch

PURPOSE: This research was done to confirm the effect of secretin on pepsin secretion and to study whether or not feeding can depress the secretin-stimulated pepsin secretion (SSPS) with its related factors. METHODS: Heidenhain (HP) and Pavlov pouches (PP) were made in 6 dogs and cannulae were then inserted into the pouches. The fluids were collected through the cannula every 10 minutes for 3 hours in various conditions, including resting, feeding, secretin perfusion, acidification of the stom-ach and, gastric distension. A modified Anson's hemoglobin method was used to check the amount of pepsin. RESULTS: When secretin was perfused in the HP, there was no increase of pepsin secretion at 0.1 and 0.2 CU/kg/hr, but the pepsin secretion increased at 0.4 and 1.0 CU/kg/hr. Compared to the control, ANOVA showed significant differences for secretin 0.4 CU/kg/hr (P<0.01) and for secretin 1.0 CU/kg/hr (P<0.001). When milk was administered through the gastric cannula after secretin stimulation, pepsin production increased in the PP, but pepsin secretion in the HP dropped close to the basal level after administering milk. This depression was not related to acidity of the milk. ANOVA showed significant differences for secretin with milk vs milk alone (P<0.0005) and vs secretin alone (P<0.0025). The inhibition of SSPS was not observed with any gastric distension or acid perfusion. CONCLUSION: In the HP, secretin increased the pepsin secretion and the vagus nerve has an inhibitory effect on pepsin secretion under secretin stimulation. Milk feeding depressed the SSPS, and that depression was not related to pH of the food and gastric distension. Further study is needed in order to clarify the mechanism of depression.

Secretin induces neurite outgrowth of PC12 through cAMP-mitogen-activated protein kinase pathway

The gastrointestinal functions of secretin have been fairly well established. However, its function and mode of action within the nervous system remain largely unclear. To gain insight into this area, we have attempted to determine the effects of secretin on neuronal differentiation. Here, we report that secretin induces the generation of neurite outgrowth in pheochromocytoma PC12 cells. The expressions of Tau and beta-tubulin, neuronal differentiation markers, are increased upon secretin stimulation. In addition, secretin induces sustained mitogen-activated protein kinase (MAPK) activation and also stimulates the cAMP secretion. Moreover, the neurite outgrowth elicited by secretin is suppressed to a marked degree in the presence of either PD98059, a specific MAPK/ERK kinase (MEK) inhibitor, or H89, a specific protein kinase A (PKA) inhibitor. Taken together, these observations demonstrate that secretin induces neurite outgrowth of PC12 cells through cAMP-MAPK pathway, and provide a novel insight into the manner in which secretin participates in neuritogenesis.

The Clinical Usefulness of Fecal Elastase-1 Test as an Exocrine Pancreatic Function Test for the Diagnosis of Chronic Pancreatitis / 대한소화기내시경학회지

BACKGROUND/AIMS: The quantitative analysis of fecal elastase-1 has been proposed as a noninvasive test for the examination of pancreatic exocrine function. Therefore, we evaluated the diagnostic value of fecal elastase-1 by comparing with endoscopic intraductal secretin test (IDST) which is used as a direct exocrine function test for the diagnosis of chronic pancreatitis. METHODS: Fecal elastase-1 concentrations were measured by ELISA in spot stool samples of 40 healthy control subjects, 21 patients with liver disease, and 12 patients with chronic pancreatitis diagnosed with endoscopic retrograde cholangiopancreatography (ERCP) and IDST. Chronic pancreatitis were then sub-classified into mild (I), moderate (II) and severe form (III), using the Cambridge classification according to ERCP finding. The linear regression analysis to evaluate the correlation between the concentration of fecal elastase-1 and IDST was performed during ERCP. The cut-off value of fecal elastase-1 to discriminate chronic pancreatitis was calculated based on receiver operating characteristic curve, and the clinical usefulness of fecal elastase-1 in the diagnosis of chronic pancreatitis was evaluated. RESULTS: There were several significant correlations between fecal elastase-1 and various parameters of IDST: pancreatic juice secretory volume (r=0.797, p<0.002), bicarbonate concentration (r=0.846, p<0.001), elastase-1 concentration in pancreatic juice (r=0.671, p<0.017), and amylase output (r=0.783, p<0.003). The mean value of fecal elastase-1 concentration in the patients with chronic pancreatitis (197+/-77microgram/g stool) was significantly lower than those in the healthy control subjects (815+/-133microgram/g stool) and patients with liver disease (594+/-206microgram/g stool) (p<0.05). The cutoff value of fecal elastase-1 to discriminate between the healthy control and chronic pancreatitis patients was 201microgram/g stool. With this cutoff value, the accuracy, sensitivity, and specificity of fecal elastase-1 to diagnose chronic pancreatitis were 78.8%, 67.7%, and 82.5%, respectively, compared to the morphological severity (the sensitivity of mild, moderate, and severe chronic pancreatitis was 33.3%, 66.7%, 83.3%, respectively). CONCLUSIONS: Measurement of fecal elastase-1 is a reliable and sensitive non-invasive test for the diagnosis of moderate to severe forms of chronic pancreatitis.

Roles of Gonadal Steroids on Exocrine Secretion of Isolated Perfused Rat Pancreas

To clarify the roles of gonadal steroids on pancreatic exocrine secretion, effects of progesterone and estradiol-17beta on spontaneous and secretagogue-induced exocrine response of isolated perfused rat pancreas were investigated. Intra-arterial infusion of progesterone resulted in significant increase of the spontaneous pancreatic fluid and amylase secretion dose-dependently. However, estradiol-17beta did not exert any influence on spontaneous pancreatic exocrine secretion. Exogenous secretin, cholecystokinin (CCK), and acetylcholine markedly stimulated pancreatic fluid and amylase secretion. Progesterone initially enhanced secretin-induced amylase secretion, but this stimulatory response declined thereafter to basal value. Moreover, secretin-induced fluid secretion was not affected by infusion of progesterone. Therefore, initial increase of secretion-induced amylase secretion by progesterone seems to be a non-specific action by washout effect of secretin. Estradiol-17beta failed to change the secretin-induced fluid and amylase secretion. Both progesterone and estradiol-17beta did not exert any influence on CCK-induced fluid and amylase secretion. Acetylcholine-induced exocrine secretion of isolated perfused pancreas also was not affected by intra-arterial infusion of progesterone or estradiol-17beta. It is concluded from the above results that progesterone could enhance the spontaneous pancreatic fluid and amylase secretion of isolated perfused rat pancreas through non-genomic short- term action, and that these effects could be masked by more potent stimulants such as secretin, CCK, and acetylcholine.

Effect of Acriflavine-Guanosine Compound (AG60) Treatment on the Gastrointestinal Endocrine Cells of Mouse Inoculated with Ehrlich Carcinoma Cells / 대한해부학회지

To study the tumor-suppression effect of a newly developed anti-tumor agent AG60 [ acriflavine (1) : guanosine (1) composition, Taerim Pharm. Co., Seoul, Korea], each Ehrlich carcinoma (107 cells)-inoculated mouse received the subcutaneous injection of 0.2 ml of saline, 5mg/kg of AG60, and 30 mg/kg of AG60, every other day for two weeks. Animals were sacrificed, and stomach, duodenum, appendix vermiformis and rectal tissues were resected and fixed in 10% neutral formalin. Tissue blocks were washed, dehydrated, embedded and cut in 6 microgram-thick sections. For immunocytochemistry, the streptavidine-biotin-peroxidse method was used with a InnoGenex (San Ramon, Calif., USA) staining kit. The tissues were incubated with rabbit antisera against somatostatin (Biogenesis, Poole, England, UK) diluted 1 : 300, secretin (Biogenesis, Poole, England, UK) diluted 1 : 2,400, neurotensin (Biogenesis, Poole, England, UK) diluted 1 : 2,600, or motilin (Biogenesis, Poole, England, UK) diluted 1 : 1,000 for 24 hour at 4dreeges C, followed by incubation in biotinylated antirabbit IgG and horseradish peroxidase-streptavidin conjugate for 1 hour at room temperature. The antigen-antibody reaction sites were visualized by incubating the sections with diaminobezidine tetrahydrochloride (DAB) for 5~15 minutes at room temperature. After mounting in canada balsam, they were examined in a Leica DM RB microscope. The number of the immunoreactive cells in the area of gastrointestinal mucosae (mean number of immunoreactive cells per 0.25mm2) were observed and calculated. The results are as follows : 1. In the fundic gland of normal mouse, somatostatin immunoreactive cells were detected (18.5+/-0.71), but neurotensin, secretin, or motilin immunoreactive cells were not found. In the duodenal mucosa of normal mouse, somatostatin immunoreactive cells were detected (7.0+/-0.10), but neurotensin, secretin or motilin immunoreactive cells were rarely found. 2. Immunoreactivity of somatostatin, secretin, neurotensin or motilin cells was not found in appendix vermiformis and rectum of normal mouse. 3. On immunocytochemical study, somatostatin immunoreactive cells in the fundic glands of normal, experimental control, AG60 (5mg/kg)-treated, AG60 (30 mg/kg)-treated and 5-fluorouracil (60 mg/kg)-treated groups were 18.5+/-0.71, 10.0+/-4.20, 11.5+/-0.71, 13.5+/-2.10, 11.5+/-2.71, respectively. 4. On immunocytochemical study, somatostatin immunoreactive cells in the duodenal mucosae of normal, experimental control, AG60 (5 mg/kg)-treated, AG60 (30 mg/kg)-treated and 5-fluorouracil (60 mg/kg)-treated groups were 7.0+/-2.10, 0.5+/-2.71, 3.0+/-1.41, 0.5+/-0.71, 2.50+/-0.71, respectively. 5. On immunocytochemical study, secretin immunoreactive cells in the duodenal mucosae of normal, experimental control, AG60 (5 mg/kg)-treated, AG60 (30 mg/kg)-treated and 5-fluorouracil (60 mg/kg)-treated groups were rarely found. 6. On immunocytochemical study, neurotensin and motilin immunoreactive cells in the duodenal mucosae of normal groups were detected, but immunoreactivies were not detected in experimental control, AG60 (5 mg/kg)-treated, AG60 (30 mg/kg)-treated or 5-fluorouracil (60 mg/kg)-treated groups.

Effects of gamma-Aminobutyric Acid on Pancreatic Amylase Secretion Evoked by Sodium Oleate in Anesthetized Rats

gamma-Aminobutyric Acid (GABA) is contained in pancreatic islet beta-cells although its physiological role in pancreatic exocrine function is completely unknown at the present time. Recently, we have reported that exogenous GABA enhances secretagogue-evoked exocrine secretion in the isolated, perfused rat pancreas. This study was aimed to investigate an effect of exogenous GABA on pancreatic exocrine secretion in vivo evoked by intestinal stimulation. Rats were anesthetized with urethane (1.4 g/kg) after 24-h fast with free access to water. GABA (10, 30 and 100micromol/kg/h), given intravenously, did not change spontaneous pancreatic amylase secretion but dose-dependently elevated the amylase secretion evoked by intraduodenal sodium oleate (0.05 mmol/h). GABA (30micromol/kg/h) also further increased the amylase secretion stimulated by CCK+(30 pmol/kg/h) plus secretin (20 pmol/kg/h) but failed to modify the amylase secretion induced by secretin alone. GABA (10, 30 and 100micromol/kg/h) also dose-dependently elevated pancreatic amylase secretion evoked by CCK+alone. Bicuculline (100micromol/kg/h), a GABAA-receptor antagonist, markedly reduced the GABA-enhanced pancreatic responses to sodium oleate, CCK+plus secretin or CCK+alone. The results indicate that GABA enhances the sodium oleate-evoked pancreatic amylase secretion via GABAA-receptors in anesthetized rats, which may account for elevating the action of CCK+released by sodium oleate.

Altered Secretory Pattern of Pancreatic Enzymes and Gastrointestinal Hormones in Streptozotocin-induced Diabetic Rats

This study was performed to investigate the pancreatic exocrine dysfunction in streptozotocin- induced diabetic rats. Changes in pancreatic enzymes secretion and in pancreatic enzymes content were observed. The output and the tissue content of amylase were significantly reduced in diabetic rats, while the output and the content of lipase were increased. Plasma secretin and cholecystokinin (CCK) concentrations of diabetic rats were significantly increased compared to those of normal rats. The altered pancreatic exocrine function was abolished by the exogenous insulin administration. The exogenous insulin also restored the increased plasma secretin and CCK concentrations. From the above results, it is suggested that, in streptozotocin-induced diabetic rats, anticoordinated changes in pancreatic enzymes secretion as well as pancreatic enzymes content are attributable to insulin deficiency and that the insulin deficiency is responsible for the increased plasma concentrations of both secretin and CCK. However, it is not clear whether the elevated plasma secretin and CCK concentrations played a direct role in changes of pancreatic exocrine function.

The Effect of Escherichia coli Lipopolysaccharide on the Flow of Bile in the Cat / 한국간담췌외과학회지

Pathophysiological conditions such as sepsis and hepatitis are frequently associated with cholestasis. Cholestasis in patients with sepsis has been attributed to the effects of endotoxin(lipopholysaccharides, LPS) and LPS-induced cytokines(TNF-a, IL-6, IL-1, etc.). LPS and cytokines reduced bile acid uptake in cultured hepatocyte. Perfusion of LPS decrease the bile flow in the isolated liver. Bile flow is increased by intravenous infusion of secretin, but it's effect remains unclear in sepsis. The aim, of this study is to elucidate the effect of LPS on the bile flow and bile composition and to test the effect of secretin on the bile flow. The animals used in this study were Korean wild cats. Under the general anesthesia, the incision was made on the midline. Common bile duct was cannulated with polyethylene tube after cholecystectomy. Bile was collected every five minutes and its volume was measured. E. coli LPS(1 mg/kg), secretin(0.1mg/kg) and H3-taurocholic acid(0.2uCi/kg) were infused via mesenteric vein. Bile was collected every 5 minutes, and the volume and its composition were analyzed. Radio-activity of the bile was quantified by Packard 1600 TR liquid scintillation analyzer. LPS of E.coli (1mg/kg) had a little effect on the blood pressure. LPS decreased the bile flow by 37% compared with the control group. Maximal impairment of the bile secretion appeared 15 minites after LPS infusion, and then secreted stablely thereafter. Secretin increased the bile flow in the normal control group. It, however, did not make any change in the bile flow after LPS infusion. LPS also reduced H3-taurocholate secretion(maximum 56%), and peak level was delayed about 10 minites compared with control group. In the composition of the bile, LPS decreased the secretion of bile acids significantly compared with the control group. Conclusively, LPS decreased the bile flow and the bile acid secretion. Secretin did not stimulate the bile flow in the LPS group. It also reduced the bile acids secretion compared with the control group. These findings will contribute to the understanding and treatment of the cholestasis and impairment of the liver function of sepsis. The findings, of reduced bile acids secretion in the LPS group may explain the pathogenesis of intrahepatic gallstone partly.