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Combination of fatty acids ameliorates exocrine pancreas ER stress induced by saturated fatty acid
S6
Abstracts / Pancreatology 16 (2016) S1eS130 1 KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Norway 2 Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh of UPMC, Pit, United States
Introduction: We have previously identified disease-associated mutations in the last exon of the CEL gene, localized in a variable number of tandem repeats (VNTR) domain. Two single base deletions (DEL1 and DEL4) lead to frameshifts, predicting a new C-terminus of the CEL protein. Patients with these mutations suffer from exocrine pancreatic dysfunction and diabetes. Aims: To understand the role of the C-terminal domain of CEL in human pancreatic disease by investigating expression, secretion and intracellular localization of different protein-variants in cellular models. Materials & methods: cDNAs of CEL-wild-type, CEL-DEL1, CEL-DEL4 and CEL-TRUNC (lacking the VNTR) were cloned into pcDNA3.1 vectors, with or without epitope tags (V5/His), and transfected into HEK293 cells. The expressed CEL-proteins were studied by Western-blotting, immunostaining and confocal imaging. Results: Forty-eight hours post-transfection all CEL-variants were detectable in the lysate, pellet and medium fractions of HEK293 cells. The amount of CEL protein in each fraction varied between variants and also depended upon the presence of epitope tags. Comparing with V5/Histagged protein variants, we observed a higher amount of untagged proteins in the pellet and less in the medium. Significantly more of the disease-causing CEL-variants were detected in the pellet as compared with the wild-type protein. When co-expressing FLAG- and V5/His-tagged CELvariants, we observed that CEL-WT could be detected in the pellet fraction together with CEL-DEL1. Conclusion: The cellular fate of CEL protein variants is highly influenced by the C-terminus of the protein. Epitope tags may cause increased solubility of disease-causing CEL variants, leading to underestimation of their propensity to aggregate in cellular model systems.
Abstract ID: 1346, Oral-20. The common G60G variant (c.180C > T) of CTRC is associated with increased risk of chronic pancreatitis in children Agnieszka Magdalena Rygiel 1, Alicja Monika Grabarczyk 1, Grzegorz Oracz 2, Aleksandra Kujko 1, Katarzyna Wertheim-Tysarowska 1, Elwira Kołodziejczyk 2, Dorota Kozieł 3, Artur Kowalik 4, Stanislaw Gluszek 3, Jerzy Bal 1 1 Department of Medical Genetics, Institute of Mother and Child Warsaw, Poland 2 Department of Gastroenterology, Hepatology and Feeding Disorders, The Children's Memorial Health Institute, Warsaw, Poland 3 Department of Surgery and Surgical Nursing, Jan Kochanowski University of Kielce, Poland 4 Department of Molecular Diagnostics, Oncology Center of the Holy Cross, Kielce, Poland
Introduction: Loss-of-function variants in chymotripsin C (CTRC) increase the risk for chronic pancreatitis (CP). The most commonly found pathogenic mutations of CTRC include K247_R254del, and R254W but their frequencies are low. Studies with adults indicated the association of G60G (c.180C>T) common variant of CTRC with CP but the available data are limited and obscure. Aims: To evaluate the risk of CP associated with CTRC mutations and G60G variant in case (CP children)-control study. Patients & methods: We sequenced exones 2-7 of the CTRC in 136 children including idiopathic CP (ICP, n¼61) and CP with various etiological factors (n¼75).Children (median age at onset 8 years) with CP verified by imaging methods were included. Control group (n¼401, median age 45) of healthy volunteers was screened by HRM-PCR and detected mutations were confirmed by direct sequencing. Results: In CP, we identified R254W(4,5%) and K247_R254del (4,5%) mutations, and G60G variant (c.180 CT or TT, 49%). Compared with
controls, CTRC mutations are associated with 7 times increased risk of CP (9% vs.1.2%, OR¼7.95% CL:2.5-19.7, P¼8,6*10-6). The c.180 CT and TT genotype is associated with 1,8 (OR¼ 1.8; 95% CL:1.3-3.2) and 15 (OR¼14.7;95% CL:5.1-42.3) times increased risk of CP with frequencies of 35% vs.18% (P¼3,5*10-4) and 15% vs.0.9% (P¼1,5*10-9), respectively. This association was also significant when ICP and control group were compared (c.180 CT: OR¼1,9; 95% CL (1.28-2.8), P¼0,0039 and c.180 TT: OR¼14.8;95% CL: 4.6-46.5, P¼3,2*10-6). Conclusion: We showed, for the first time that G60G variant of CTRC, especially c.180 TT genotype is strongly associated with idiopathic CP in children.
Abstract ID: 1350. HENT-1 and deoxycytidine kinase as molecular markers in pancreatic cancer Katarzyna Gardian, Marek Durlik Mossakowski Medical Research Institute, Poland Introduction: Pancreatic cancer remains the most aggressive malignancy of all human cancers. Patients have an extremely poor prognosis, with a median survival period of 6 months. Gemcitabine remains as main therapeutic agent in pancreatic cancer although its efficacy is not high. HENT-1 and deoxycytydine kinase DCK were associated with gemcitabine resistance and HENT-1 was recognizes as indicator of treatment effectiveness. In our research we wanted to study if double evaluation of HENT-1 and DCK would have better prognostic value in gemcitabine treatment. Aims: To evaluate expression of HENT-1 and DCK and study their prognostic value as molecular markers of survival in patients treated with gemcitabine . Materials & methods: Tumor tissue samples were obtained from 20 patients, who underwent curative resection. Median overall survival was 14 months (2-36 months). Patients received at least one course of treatment with gemcitabine. Tissue specimens were analyzed with immunohistochemistry using antibodies against HENT-1 (SP-120) and DCK (3F5) using ImmPRESS Detection Kit. Results: We found strong HENT-1 expression in acinar and ductal cells in normal pancreas. In cancer cells staining for HENT-1 was seen as very week to moderate. Semi-quantitative comparison confirmed that higher expression of HENT-1 is associated with extended survival up to 15 months.In normal ductale cells DCK expression was moderate and in cancer cells staining was very weak or there was no reaction. We did not observed any association on level of DCK and survival. Conclusion: HENT-1 has a prognostic value in patients treated with gemcitabine, staining against deoxycytidine kinase does not bring any additional value.
Abstract ID: 1353. Combination of fatty acids ameliorates exocrine pancreas ER stress induced by saturated fatty acid Ruth Birk, Karin Ben-Dror Department of Nutrition, Health Science Faculty, Ariel University, Israel Introduction: We have previously shown that fatty acids have differential effects on ER stress. Where saturated fatty acis (FAs) induce lipotoxicity and ER stress. High levels of serum fatty acids are typical to obesity, which is a risk factor in the etiology of pancreatitis and pancreatic cancer. Aims: We now studied the effect of acute exposure to combination of various FAs at different concentrations on exocrine acinar cells stress. Materials & methods: We challenged AR42J and primary exocrine pancreas models with combination of FAs at normal and overload
Abstracts / Pancreatology 16 (2016) S1eS130
concentrations (typical to obesity), analyzing fat accumulation and ER stress indicators. Results: Pancreatic acinar cells acutely challenged with different FAs exhibited significantly increased fat accumulation. Acute challenge with saturated FA in obesogenic levels significantly increased stress levels, unlike challenge with unsaturated FA, reflected by; increased expression levels of inflammatory and ER stress markers and XBP1 splicing and nuclear translocation. Combination of FAs reduced the deleterious stress effects induced by saturated FA. Conclusion: Thus, type of FA differentially affects exocrine pancreas acinar cell stress, especially in obesogenic levels. Combination of FAs ameliorates exocrine pancreas acinar stress and could have potential therapeutic nutritional implications relevant to pancreatitis and pancreatic cancer nutritional treatment.
Abstract ID: 1357. Reduced synthesis of TNF alpha by ghrelin in acute pancreatitis Joanna Bonior 1, Piotr Ceranowicz 2, Piotr Pierzchalski 1, Michalina Kot 1, Artur Dembinski 2, Zygmunt Warzecha 2, Jolanta Jaworek 1 1 Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland 2 Department of Physiology, Jagiellonian University Medical College, Krakow, Poland
Introduction: Ghrelin (GHRL), a 28-amino acid polypeptide, that was originally isolated from the stomach, was shown to protect the pancreas from caerulein-induced pancreatitis (AP). Aims: To determine the effects of GHRL on tumor necrosis factor-alpha (TNF-L) concentration in the rats with AP and on the signals for growth hormone secretagogues receptor type 1a (GHS-R1a) and TNF-L in the pancreatic acini. Materials & methods: AP was induced by caerulein infusion (25 ug/kg s.c.). GHRL (12.5; 25; 50 ug/kg i.p.) was given to the control rats and prior to the start of inflammation in vivo. Plasma TNF-L concentration was measured by ELISA. Pancreatic acini were isolated from control, GHRL rats and then hyperstimulated by caerulein (10-8 M) in vitro. The gene expressions were determined by RT-PCR and the protein contents by Western-blot. Results: Administration of GHRL to the control rats failed to affect TNFL concentration in plasma. AP significantly increased its, but application of GHRL prior to the inflammation significantly dose-dependently reduced this pro-inflammatory cytokine. Protein expressions and mRNA signals for GHS-R1a and TNF-L have been detected in the pancreatic acini under basal conditions and GHRL resulted in a statistically increase of GHS-R1a without changing signals of TNF-L. Caerulein significantly changed the test signals: downregulated receptor and upregulated cytokine. These adverse effects were reversed by GHRL. Conclusion: Caerulein upregulated molecular signals for TNF-L and downregulated that for GHS-R1a in the pancreatic acini. This effect could be prevented by pretreatment of the AP rats with GHRL. Above mechanism could be implicated in the protective action of this polypeptide in AP.
Abstract ID: 1369.
S7
Aims: We aimed to evaluate the protective effects of enoxaparin in Lornithineeinduced acute pancreatitis in rats. Materials & methods: We used Wistar albino rats for this study. Rats were divided into 3 groups: control group, and groups that were administered L-ornithine (Group 2), enoxaparin after induction of acute pancreatitis (Group 3). Measurement of the myeloperoxidase, catalase, malondialdehyde, and nitric oxide levels in pancreas tissue as indices of tissue oxidative capacity and inflammation were used to evaluate pancreatitis. Results: Acute necrotizing severe pancreatitis was induced in groups 2 and 3 by L-ornithine injections. A significant decrease in the catalase activity (the activity was on 9.21% less than in control group), and increased in the myeloperoxidase activity (the activity was on 103.99% higher than in control group) and malondialdehyde levels (the level was on 160.78% higher than in control group) was observed in rats with acute pancreatitis. Enoxaparin significantly decreased the myeloperoxidase activity and levels of malondialdehyde and nitric oxide, increased the activity of catalase in these rats. Conclusion: This study demonstrates the powerful therapeutic potential of the enoxaparin that are clinically applied for anticoagulant or anti-inflammatory properties. Use of enoxaparin revealed significant reductions in L-ornithine-induced alterations, including inflammation and oxidative stress. However, further investigations are required to establish its roles in the acute pancreatitis.
Abstract ID: 1378. Luminal L-kynurenine stimulates pancreatic exocrine secretion via activation of sensory nerves Katarzyna Nawrot-Porabka, Anna Leja-Szpak, Joanna Szklarczyk, Joanna Bonior, Michalina Kot, Jolanta Jaworek Jagiellonian University, School of Medicine, Faculty of Health Care, Department of Medical Physiology, Poland Introduction: The kynurenines known as the products of tryptophan metabolism, are involved in many of physiological processes as well as in regulation of the immune defence. These substances have been detected in the digestive tract, but their effects on pancreatic exocrine function have not been substantially investigated. Aims: To assess the effects of intraduodenal (i.d.) infusion of L-kynurenine on pancreatic amylase secretion under basal conditions and involvement of sensory nerves in this process. Materials & methods: The study was performed on Wistar rats weighing 350g. Under anesthesia the animals were surgically equipped with silicone catheters, inserted into pancreato-biliary duct, and into duodenum. L-kynurenine (5, 50 or 250 mg/kg i.d.) was given as a bolus into duodenum lumen. In the part of study rats with sensory nerves deactivated by capsaicin were employed. Capsaicin deactivation (CD) of sensory fibers was performed by subcutaneous application of this compound at total dose of 100 mg/kg. During all of experiments the samples of pancreato-biliary juice were collected to measure amylase outputs. Results: Intraduodudenal administration of L-kynurenine resulted in dose-dependent increase of pancreatic amylase secretion. Deactivation of sensory fibers resulted in complete reversion of above effects of Lkynurenine. Conclusion: Sensory nerves are involved in the stimulatory effects of tryptophan metabolite, L-kynurenine, on exocrine pancreatic secretion in the rats.
Enoxaparin protective effect in experimental acute necrotizing pancreatitis Serge Chooklin, Serhii Chuklin, Bohdan Pidhirny Regional Clinical Hospital, Lviv, Ukraine Introduction: Coagulative disorders occur in acute pancreatitis and are related to the severity of this disease. Some experimental studies have shown anti-inflammatory effect of heparin, including the protective and therapeutic effect of heparin in acute pancreatitis.
Abstract ID: 1382. EUS-FNA of a pancreas: A clinical-pathological correlation of infrequent intraductal papillary mucinous neoplasms (IPMN) Jarmila Sustikova 1, Magdalena Uvirova 1, Dusan Ziak 2, Vladimir Zidlik 2, Pavel Hurnik 2, Ondrej Urban 3, Jana Dvorackova 2
Abstracts / Pancreatology 16 (2016) S1eS130 1 KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Norway 2 Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh of UPMC, Pit, United States
Introduction: We have previously identified disease-associated mutations in the last exon of the CEL gene, localized in a variable number of tandem repeats (VNTR) domain. Two single base deletions (DEL1 and DEL4) lead to frameshifts, predicting a new C-terminus of the CEL protein. Patients with these mutations suffer from exocrine pancreatic dysfunction and diabetes. Aims: To understand the role of the C-terminal domain of CEL in human pancreatic disease by investigating expression, secretion and intracellular localization of different protein-variants in cellular models. Materials & methods: cDNAs of CEL-wild-type, CEL-DEL1, CEL-DEL4 and CEL-TRUNC (lacking the VNTR) were cloned into pcDNA3.1 vectors, with or without epitope tags (V5/His), and transfected into HEK293 cells. The expressed CEL-proteins were studied by Western-blotting, immunostaining and confocal imaging. Results: Forty-eight hours post-transfection all CEL-variants were detectable in the lysate, pellet and medium fractions of HEK293 cells. The amount of CEL protein in each fraction varied between variants and also depended upon the presence of epitope tags. Comparing with V5/Histagged protein variants, we observed a higher amount of untagged proteins in the pellet and less in the medium. Significantly more of the disease-causing CEL-variants were detected in the pellet as compared with the wild-type protein. When co-expressing FLAG- and V5/His-tagged CELvariants, we observed that CEL-WT could be detected in the pellet fraction together with CEL-DEL1. Conclusion: The cellular fate of CEL protein variants is highly influenced by the C-terminus of the protein. Epitope tags may cause increased solubility of disease-causing CEL variants, leading to underestimation of their propensity to aggregate in cellular model systems.
Abstract ID: 1346, Oral-20. The common G60G variant (c.180C > T) of CTRC is associated with increased risk of chronic pancreatitis in children Agnieszka Magdalena Rygiel 1, Alicja Monika Grabarczyk 1, Grzegorz Oracz 2, Aleksandra Kujko 1, Katarzyna Wertheim-Tysarowska 1, Elwira Kołodziejczyk 2, Dorota Kozieł 3, Artur Kowalik 4, Stanislaw Gluszek 3, Jerzy Bal 1 1 Department of Medical Genetics, Institute of Mother and Child Warsaw, Poland 2 Department of Gastroenterology, Hepatology and Feeding Disorders, The Children's Memorial Health Institute, Warsaw, Poland 3 Department of Surgery and Surgical Nursing, Jan Kochanowski University of Kielce, Poland 4 Department of Molecular Diagnostics, Oncology Center of the Holy Cross, Kielce, Poland
Introduction: Loss-of-function variants in chymotripsin C (CTRC) increase the risk for chronic pancreatitis (CP). The most commonly found pathogenic mutations of CTRC include K247_R254del, and R254W but their frequencies are low. Studies with adults indicated the association of G60G (c.180C>T) common variant of CTRC with CP but the available data are limited and obscure. Aims: To evaluate the risk of CP associated with CTRC mutations and G60G variant in case (CP children)-control study. Patients & methods: We sequenced exones 2-7 of the CTRC in 136 children including idiopathic CP (ICP, n¼61) and CP with various etiological factors (n¼75).Children (median age at onset 8 years) with CP verified by imaging methods were included. Control group (n¼401, median age 45) of healthy volunteers was screened by HRM-PCR and detected mutations were confirmed by direct sequencing. Results: In CP, we identified R254W(4,5%) and K247_R254del (4,5%) mutations, and G60G variant (c.180 CT or TT, 49%). Compared with
controls, CTRC mutations are associated with 7 times increased risk of CP (9% vs.1.2%, OR¼7.95% CL:2.5-19.7, P¼8,6*10-6). The c.180 CT and TT genotype is associated with 1,8 (OR¼ 1.8; 95% CL:1.3-3.2) and 15 (OR¼14.7;95% CL:5.1-42.3) times increased risk of CP with frequencies of 35% vs.18% (P¼3,5*10-4) and 15% vs.0.9% (P¼1,5*10-9), respectively. This association was also significant when ICP and control group were compared (c.180 CT: OR¼1,9; 95% CL (1.28-2.8), P¼0,0039 and c.180 TT: OR¼14.8;95% CL: 4.6-46.5, P¼3,2*10-6). Conclusion: We showed, for the first time that G60G variant of CTRC, especially c.180 TT genotype is strongly associated with idiopathic CP in children.
Abstract ID: 1350. HENT-1 and deoxycytidine kinase as molecular markers in pancreatic cancer Katarzyna Gardian, Marek Durlik Mossakowski Medical Research Institute, Poland Introduction: Pancreatic cancer remains the most aggressive malignancy of all human cancers. Patients have an extremely poor prognosis, with a median survival period of 6 months. Gemcitabine remains as main therapeutic agent in pancreatic cancer although its efficacy is not high. HENT-1 and deoxycytydine kinase DCK were associated with gemcitabine resistance and HENT-1 was recognizes as indicator of treatment effectiveness. In our research we wanted to study if double evaluation of HENT-1 and DCK would have better prognostic value in gemcitabine treatment. Aims: To evaluate expression of HENT-1 and DCK and study their prognostic value as molecular markers of survival in patients treated with gemcitabine . Materials & methods: Tumor tissue samples were obtained from 20 patients, who underwent curative resection. Median overall survival was 14 months (2-36 months). Patients received at least one course of treatment with gemcitabine. Tissue specimens were analyzed with immunohistochemistry using antibodies against HENT-1 (SP-120) and DCK (3F5) using ImmPRESS Detection Kit. Results: We found strong HENT-1 expression in acinar and ductal cells in normal pancreas. In cancer cells staining for HENT-1 was seen as very week to moderate. Semi-quantitative comparison confirmed that higher expression of HENT-1 is associated with extended survival up to 15 months.In normal ductale cells DCK expression was moderate and in cancer cells staining was very weak or there was no reaction. We did not observed any association on level of DCK and survival. Conclusion: HENT-1 has a prognostic value in patients treated with gemcitabine, staining against deoxycytidine kinase does not bring any additional value.
Abstract ID: 1353. Combination of fatty acids ameliorates exocrine pancreas ER stress induced by saturated fatty acid Ruth Birk, Karin Ben-Dror Department of Nutrition, Health Science Faculty, Ariel University, Israel Introduction: We have previously shown that fatty acids have differential effects on ER stress. Where saturated fatty acis (FAs) induce lipotoxicity and ER stress. High levels of serum fatty acids are typical to obesity, which is a risk factor in the etiology of pancreatitis and pancreatic cancer. Aims: We now studied the effect of acute exposure to combination of various FAs at different concentrations on exocrine acinar cells stress. Materials & methods: We challenged AR42J and primary exocrine pancreas models with combination of FAs at normal and overload
Abstracts / Pancreatology 16 (2016) S1eS130
concentrations (typical to obesity), analyzing fat accumulation and ER stress indicators. Results: Pancreatic acinar cells acutely challenged with different FAs exhibited significantly increased fat accumulation. Acute challenge with saturated FA in obesogenic levels significantly increased stress levels, unlike challenge with unsaturated FA, reflected by; increased expression levels of inflammatory and ER stress markers and XBP1 splicing and nuclear translocation. Combination of FAs reduced the deleterious stress effects induced by saturated FA. Conclusion: Thus, type of FA differentially affects exocrine pancreas acinar cell stress, especially in obesogenic levels. Combination of FAs ameliorates exocrine pancreas acinar stress and could have potential therapeutic nutritional implications relevant to pancreatitis and pancreatic cancer nutritional treatment.
Abstract ID: 1357. Reduced synthesis of TNF alpha by ghrelin in acute pancreatitis Joanna Bonior 1, Piotr Ceranowicz 2, Piotr Pierzchalski 1, Michalina Kot 1, Artur Dembinski 2, Zygmunt Warzecha 2, Jolanta Jaworek 1 1 Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland 2 Department of Physiology, Jagiellonian University Medical College, Krakow, Poland
Introduction: Ghrelin (GHRL), a 28-amino acid polypeptide, that was originally isolated from the stomach, was shown to protect the pancreas from caerulein-induced pancreatitis (AP). Aims: To determine the effects of GHRL on tumor necrosis factor-alpha (TNF-L) concentration in the rats with AP and on the signals for growth hormone secretagogues receptor type 1a (GHS-R1a) and TNF-L in the pancreatic acini. Materials & methods: AP was induced by caerulein infusion (25 ug/kg s.c.). GHRL (12.5; 25; 50 ug/kg i.p.) was given to the control rats and prior to the start of inflammation in vivo. Plasma TNF-L concentration was measured by ELISA. Pancreatic acini were isolated from control, GHRL rats and then hyperstimulated by caerulein (10-8 M) in vitro. The gene expressions were determined by RT-PCR and the protein contents by Western-blot. Results: Administration of GHRL to the control rats failed to affect TNFL concentration in plasma. AP significantly increased its, but application of GHRL prior to the inflammation significantly dose-dependently reduced this pro-inflammatory cytokine. Protein expressions and mRNA signals for GHS-R1a and TNF-L have been detected in the pancreatic acini under basal conditions and GHRL resulted in a statistically increase of GHS-R1a without changing signals of TNF-L. Caerulein significantly changed the test signals: downregulated receptor and upregulated cytokine. These adverse effects were reversed by GHRL. Conclusion: Caerulein upregulated molecular signals for TNF-L and downregulated that for GHS-R1a in the pancreatic acini. This effect could be prevented by pretreatment of the AP rats with GHRL. Above mechanism could be implicated in the protective action of this polypeptide in AP.
Abstract ID: 1369.
S7
Aims: We aimed to evaluate the protective effects of enoxaparin in Lornithineeinduced acute pancreatitis in rats. Materials & methods: We used Wistar albino rats for this study. Rats were divided into 3 groups: control group, and groups that were administered L-ornithine (Group 2), enoxaparin after induction of acute pancreatitis (Group 3). Measurement of the myeloperoxidase, catalase, malondialdehyde, and nitric oxide levels in pancreas tissue as indices of tissue oxidative capacity and inflammation were used to evaluate pancreatitis. Results: Acute necrotizing severe pancreatitis was induced in groups 2 and 3 by L-ornithine injections. A significant decrease in the catalase activity (the activity was on 9.21% less than in control group), and increased in the myeloperoxidase activity (the activity was on 103.99% higher than in control group) and malondialdehyde levels (the level was on 160.78% higher than in control group) was observed in rats with acute pancreatitis. Enoxaparin significantly decreased the myeloperoxidase activity and levels of malondialdehyde and nitric oxide, increased the activity of catalase in these rats. Conclusion: This study demonstrates the powerful therapeutic potential of the enoxaparin that are clinically applied for anticoagulant or anti-inflammatory properties. Use of enoxaparin revealed significant reductions in L-ornithine-induced alterations, including inflammation and oxidative stress. However, further investigations are required to establish its roles in the acute pancreatitis.
Abstract ID: 1378. Luminal L-kynurenine stimulates pancreatic exocrine secretion via activation of sensory nerves Katarzyna Nawrot-Porabka, Anna Leja-Szpak, Joanna Szklarczyk, Joanna Bonior, Michalina Kot, Jolanta Jaworek Jagiellonian University, School of Medicine, Faculty of Health Care, Department of Medical Physiology, Poland Introduction: The kynurenines known as the products of tryptophan metabolism, are involved in many of physiological processes as well as in regulation of the immune defence. These substances have been detected in the digestive tract, but their effects on pancreatic exocrine function have not been substantially investigated. Aims: To assess the effects of intraduodenal (i.d.) infusion of L-kynurenine on pancreatic amylase secretion under basal conditions and involvement of sensory nerves in this process. Materials & methods: The study was performed on Wistar rats weighing 350g. Under anesthesia the animals were surgically equipped with silicone catheters, inserted into pancreato-biliary duct, and into duodenum. L-kynurenine (5, 50 or 250 mg/kg i.d.) was given as a bolus into duodenum lumen. In the part of study rats with sensory nerves deactivated by capsaicin were employed. Capsaicin deactivation (CD) of sensory fibers was performed by subcutaneous application of this compound at total dose of 100 mg/kg. During all of experiments the samples of pancreato-biliary juice were collected to measure amylase outputs. Results: Intraduodudenal administration of L-kynurenine resulted in dose-dependent increase of pancreatic amylase secretion. Deactivation of sensory fibers resulted in complete reversion of above effects of Lkynurenine. Conclusion: Sensory nerves are involved in the stimulatory effects of tryptophan metabolite, L-kynurenine, on exocrine pancreatic secretion in the rats.
Enoxaparin protective effect in experimental acute necrotizing pancreatitis Serge Chooklin, Serhii Chuklin, Bohdan Pidhirny Regional Clinical Hospital, Lviv, Ukraine Introduction: Coagulative disorders occur in acute pancreatitis and are related to the severity of this disease. Some experimental studies have shown anti-inflammatory effect of heparin, including the protective and therapeutic effect of heparin in acute pancreatitis.
Abstract ID: 1382. EUS-FNA of a pancreas: A clinical-pathological correlation of infrequent intraductal papillary mucinous neoplasms (IPMN) Jarmila Sustikova 1, Magdalena Uvirova 1, Dusan Ziak 2, Vladimir Zidlik 2, Pavel Hurnik 2, Ondrej Urban 3, Jana Dvorackova 2