Secretory Trypsin Research Articles

Effect of an Early Mobilization Program on Functional Capacity after Coronary Artery Bypass Surgery a Systemic Review

Phenylalanine function stabilized by lysine which found on lysosomal surface, that Phe necessary to regulate the synthesis or secretion of α-amylase, trypsin and lipase, where the Severe acute pancreatitis in a child with phenylketonuria. The phenylketonuria due to decreased lysine followed by lysosomal dysfunction that will be result of deficiency in phenylalanine function that will not form pancreatic enzymes and stomach enzyme and will be accumulated. The Lysosomal dysfunction will be result of accumulation of undigested polymer including inflammation which play important roles in pathophysiology, that reflect reduction in lysine acylation followed by reduction in aminoacyl tRNAs which promote Phe and E coli functions for activating protein and mRNAs synthesis, that will be followed by increasing in TNf-a synthesis (and reduction in VEGF-As ) which activate NK (not beings related to human immune proper function ) which regulated by the undigested polymers in random pathways stimulated by TNf-a functional pathway (activated by NLRP3 inflammasome. Retinoic acid is necessary to promote lysine acylation which regulate aminoacyl-tRNAs production regulated by mitochondrial enzymes, which regulate mRNA production by E coli (regulated by phenylalanine) that necessary to run antioxidant functions and cellular biosynthesis. Lysine acetylation so important to regulates the activity of Escherichia coli Sadenosylmethionine synthase. RNA (produced by E coli) is 2′-O-methylated demonstrated higher stability that can improve immune by promoting anti-inflammatory processes and improve myocardial functions, and adopt heart constriction by activating NR4As pathway. The antihypertensive pathway mechanism is: the Lysine ¬¬>activate ATPase (stimulate retinoic acid “RA” ) ¬¬>Lysine acetylation ¬¬> promote Phe/ hydroxylase ¬¬> followed by ¬>activate Tyr/ hydroxylase ¬>activate dopamine ¬> activate NR4As pathway ¬>GC-beta ¬>activate both of Oxytocin and Nrf2 ¬> Ang2-AT2 and VEGF-A productive functions ¬>heme oxygenase ¬>anti-inflammatory growth and processes. Lysine Methylation has important role in adopt hypertension through activating pervious Antihypertensive pathway mediated by Phe hydroxylase synthesis and Tyr hydroxylase production followed by activating both of dopamine and NR4As pathway. The oxidation of phenylalanyl-tRNA synthetase positively regulates translational quality control, and regulates the initiation of digestive enzyme mRNA translation, where consecutive AAA-lysines is paused for encoding Phe followed by ribosome sliding on homopolymeric A sequence. That lysine activates mitochondria function followed by promoting Phenylalanine and phenylalanine-tRNAs productions by translations within E coli, followed by Phe/ hydroxylase activate Tyr hydroxylase production which activate dopamine synthesis. And positively, Lysine is the most effective amino acid for activating all of ATPase, GTPase, and lysosomes, and E coli functions, where ATPase necessary for activating lysine Phosphorylation for activating lysosome digestion, followed by activating E coli through activating Phe hydroxylase production, while GTPase necessary for activating mitochondrial repairs, which act on pro-inflammation and cholesterol for activating estrogen production and activating the NR4As pathway which activate all of Oxytocin, Nrf2 followed by Ang2-AT2 and VEGF-A production and then followed by activating heme oxygenase and anti-inflammatory growth and processes that prevent LV-hypertrophy, and prevent coronary calcification.

Derivation of pancreatic acinar cell carcinoma cell line HS-1 as a patient-derived tumor organoid.

Acinar cell carcinoma (ACC) of the pancreas is a malignant tumor of the exocrine cell lineage with a poor prognosis. Due to its rare incidence and technical difficulties, few authentic human cell lines are currently available, hampering detailed investigations of ACC. Therefore, we applied the organoid culture technique to various types of specimens, such as bile, biopsy, and resected tumor, obtained from a single ACC patient. Despite the initial propagation, none of these organoids achieved long-term proliferation or tolerated cryopreservation, confirming the challenging nature of establishing ACC cell lines. Nevertheless, the biopsy-derived early passage organoid developed subcutaneous tumors in immunodeficient mice. The xenograft tumor histologically resembled the original tumor and gave rise to infinitely propagating organoids with solid features and high levels of trypsin secretion. Moreover, the organoid stained positive for carboxylic ester hydrolase, a specific ACC marker, but negative for the duct cell marker CD133 and the endocrine lineage marker synaptophysin. Hence, we concluded the derivation of a novel ACC cell line of the pure exocrine lineage, designated HS-1. Genomic analysis revealed extensive copy number alterations and mutations in EP400 in the original tumor, which were enriched in primary organoids. HS-1 displayed homozygous deletion of CDKN2A, which might underlie xenograft formation from organoids. Although resistant to standard cytotoxic agents, the cell line was highly sensitive to the proteasome inhibitor bortezomib, as revealed by an in vitro drug screen and in vivo validation. In summary, we document a novel ACC cell line, which could be useful for ACC studies in the future.

Salidroside alleviates taurolithocholic acid 3-sulfate-induced AR42J cell injury

ObjectivesTo investigate the protective effects of Salidroside (Sal) on AP cell model induced by taurolithocholic acid 3-sulfate (TLC-S) as well as its underlying mechanism. MethodsAR42J cells were divided into normal group (N group), AP cell model group (Mod group), Sal treated alone group (S+N group) and Sal treated AP cell model group (S+Mod group). The cell viability was examined by CCK-8 assay. Secretion of lipase and trypsin by AR42J cells, quantified using commercial assay kits, was used as the markers of TLC-S-induced pancreatitis. The levels of TNF-α, IL-1β, IL-8, IL-6 and IL-10 in the cell supernatant were measured by ELISA. The effect of Sal on molecules in the NF-κB signaling pathway and autophagy was investigated by qRT-PCR and western blot. ResultsThe decreased cell viability in Mod group was increased by Sal (P < 0.01). The upheaved activities of lipase and trypsin in AP cell model were declined by Sal (P < 0.01). The levels of TNF-α, IL-1β, IL-8 and IL-6 in the cell supernatant, Beclin-1 and LC3-Ⅱ mRNA and protein, p-p65/p65 protein, which were increased in AP cell model, were decreased by Sal; and IL-10 in the cell supernatant, LAMP2 mRNA and protein, p-IκBα/IκBα protein which was declined in AP cell model, was increased by Sal (P < 0.05 or 0.01). There were no significant differences in all indexes between the N and S+N groups (P > 0.05). ConclusionsSal alleviated AR42J cells injury induced by TLC-S, inhibited the inflammatory responses and modulated the autophagy, mainly through inhibiting the NF-κB signaling pathway.

The Effects of Trypsin Inhibitor on Insulin Secretion Using Rat Pancreas in an Organ Bath.

We developed an experimental method to reproduce insulin secretion from isolated rat pancreas preparations using an organ bath system. However, secretion of trypsin, another pancreatic enzyme, interferes with insulin production in such systems. We aimed to ascertain the minimum trypsin inhibitor (TI), dose for obtaining a sustained, stable rate of insulin secretion. The action of TI (1-10 μg/ml) on pancreatic preparations of male Wistar-Imamichi rats in organ bath experiments was assessed by measuring insulin, amylase, and trypsin activity. The level of insulin outflow remained steady in the TI-treated samples, in contrast to that in the untreated control, where insulin secretion decreased over time. The level of amylase outflow did not change significantly. Trypsin activity was significantly lower in the TI-treated samples than in the control. Even low concentrations of TI can maintain insulin secretion by inhibiting trypsin activity in organ bath experiments.

Zonation of Pancreatic Acinar Cells in Diabetic Mice

SummaryThe islets of Langerhans are dynamic structures that can change in size, number of cells, and molecular function in response to physiological and pathological stress. Molecular cues originating from the surrounding “peri-islet” acinar cells that could facilitate this plasticity have not been explored. Here, we combine single-molecule transcript imaging in the intact pancreas and transcriptomics to identify spatial heterogeneity of acinar cell gene expression. We find that peri-islet acinar cells exhibit a distinct molecular signature in db/db diabetic mice that includes upregulation of trypsin family genes and elevated mTOR activity. This zonated expression program seems to be induced by CCK that is secreted from islet cells. Elevated peri-islet trypsin secretion could facilitate the islet expansion observed in this model via modulation of the islet capsule matrix components. Our study highlights a molecular axis of communication between the pancreatic exocrine and endocrine compartments that may be relevant to islet expansion.

The lysine derivative aminoadipic acid, a biomarker of protein oxidation and diabetes-risk, induces production of reactive oxygen species and impairs trypsin secretion in mouse pancreatic acinar cells

We have examined the effects of α-aminoadipic acid, an oxidized derivative from the amino acid lysine, on the physiology of mouse pancreatic acinar cells. Changes in intracellular free-Ca2+ concentration, the generation of reactive oxygen species, the levels of carbonyls and thiobarbituric-reactive substances, cellular metabolic activity and trypsin secretion were studied. Stimulation of mouse pancreatic cells with cholecystokinin (1 nM) evoked a transient increase in [Ca2+]i. In the presence of α-amoniadipic acid increases in [Ca2+]i were observed. In the presence of the compound, cholecystokinin induced a Ca2+ response that was smaller compared with that observed when cholecystokinin was applied alone. Stimulation of cells with cholecystokinin in the absence of Ca2+ in the extracellular medium abolished further mobilization of Ca2+ by α-aminoadipic acid. In addition, potential pro-oxidant conditions, reflected as increases in ROS generation, oxidation of proteins and lipids, were noted in the presence of α-aminoadipic acid. Finally, the compound impaired trypsin secretion induced by the secretagogue cholecystokinin. We conclude that the oxidized derivative from the amino acid lysine induces pro-oxidative conditions and the impairment of enzyme secretion in pancreatic acinar cells. α-aminoadipic acid thus creates a situation that could potentially lead to disorders in the physiology of the pancreas.

The melatonin receptor antagonist luzindole induces Ca2+ mobilization, reactive oxygen species generation and impairs trypsin secretion in mouse pancreatic acinar cells

BackgroundIn this work we studied the effects of the melatonin receptor-antagonist luzindole (1 μM–50 μM) on isolated mouse pancreatic acinar cells. MethodsChanges in intracellular free-Ca2+ concentration, reactive oxygen species production and trypsin secretion were analyzed. ResultsLuzindole induced increases in [Ca2+]i that diminished CCK-8 induced Ca2+ mobilization, compared with that observed when CCK-8 was applied alone. Treatment of cells with thapsigargin (1 μM), in the absence of Ca2+ in the extracellular medium, evoked a transient increase in [Ca2+]i. The additional incubation of cells with luzindole (10 μM) failed to induce further mobilization of Ca2+. In the presence of luzindole a concentration-dependent increase in ROS generation was observed that decreased in the absence of Ca2+ or by pretreatment of cells with melatonin (100 μM). Incubation of pancreatic acinar cells with luzindole (10 μM) impaired CCK-8-induced trypsin secretion. Melatonin was unable to revert the effect of luzindole on CCK-8-induced trypsin secretion. ConclusionThe melatonin receptor-inhibitor luzindole induces Ca2+-mediated pro-oxidative conditions and impairment of enzyme secretion, which creates a situation in pancreatic acinar cells that might compromise their function. General significanceThe effects of luzindole that we have observed, might be unspecific and could mislead the observations when it is used to study the actions of melatonin on the gland. Another possibility is that melatonin receptors exhibit a basal or agonist-independent activity in pancreatic acinar cells, which might be modulated by melatonin or luzindole.

Sulfanilic acid increases intracellular free-calcium concentration, induces reactive oxygen species production and impairs trypsin secretion in pancreatic AR42J cells

We studied the effects of the tartrazine-metabolite sulfanilic acid on the physiology of pancreatic AR42J cells. Sulfanilic acid (1 μM-1 mM) induced a slow and progressive increase in intracellular free-calcium concentration that reached a plateau. The effect of sulfanilic acid was not concentration-dependent. Stimulation of cells with thapsigargin (1 μM) after treatment with sulfanilic acid (1 mM) induced a smaller Ca2+ response compared with that obtained with thapsigargin alone. Sulfanilic acid induced a concentration-dependent production of reactive oxygen species; however, this effect was not Ca2+-dependent. Depolarization of mitochondrial membrane potential was observed at the concentration of 1 mM sulfanilic acid. In the presence of the compound a decrease in the GSH/GSSG ratio was observed. A decrease in the expression of superoxide dismutase 2 was noted. Finally, stimulation of cells with CCK-8 led to a concentration-dependent increase of trypsin secretion that was impaired by pretreatment of cells with sulfanilic acid. Preincubation of cells with the antioxidant melatonin (100 μM) reduced the effect of sulfanilic acid on trypsin secretion. We conclude that sulfanilic acid might induce oxidative stress, which could alter Ca2+ signaling and enzyme secretion in pancreatic AR42J cells. This creates a situation potentially leading to damage of the exocrine pancreas.

Effects of dietary soybean meal on the digestive physiology of red seabream Pagrus major

To clarify the effects of dietary soybean meal (SBM) on the digestive physiology of red seabream Pagrus major, two isonitrogenous and isolipidic diets; a fishmeal-based diet (diet FM) and a SBM-based diet (diet SBM), were prepared and the acute and chronic effects of the diets on the digestive physiology of the fish were examined. In the acute effects trial (<48 h), the only difference observed was a lower level of trypsin activity in the intestinal content of the SBM group than the FM group, indicating that SBM administration reduces trypsin secretion on a short-term basis. In the chronic effects trial (six weeks), there were clear differences in several parameters assessed. There was a clear retardation of growth in fish fed the SBM diet, in addition to a faster gastric transit rate, stacked intestinal content, lower gallbladder weight, lower activities/gene expression levels of hepatopancreatic enzymes (trypsin, chymotrypsin, amylase and/or lipase) and reduced protease activity (trypsin and chymotrypsin) in the intestinal content compared to fish fed the FM diet. Taken together, these results indicate that feeding SBM over a long period (chronic exposure) leads to reduced storage, production and secretion of bile and pancreatic digestive enzymes. SBM protein does not appear to fully activate or stimulate the digestive system of red seabream in either the short or long term. This may be due to a lack of stimulation or to an inhibitory effect that becomes more pronounced on a long-term basis. Such inhibition of the digestive process may be one of the main reasons for the low growth performance observed in fish fed SBM-based diets.

Phenylalanine regulates initiation of digestive enzyme mRNA translation in pancreatic acinar cells and tissue segments in dairy calves.

As new nutritional strategies for ruminant are designed to change production efficiency by improving the supply of rumen protect protein, lipid, and even starch, the digestive system must fit to utilize these increased nutrient supplies, especially the pancreas. The objective of this study was to investigate the effects of phenylalanine (Phe) on digestive enzymes synthesis or secretion and cellular signaling in pancreatic acinar (PA) cells of dairy calves. The PA cells isolated from fresh pancreas of dairy calves, and cultured in completed RIPA 1640 medium with no fetal serum but 0, 0.15 and 0.45 mM Phe at 37°C in CO2 incubator for 120 min. The pancreatic tissue segments (PTS) was cut approximately 2 × 2 mm from the fresh pancreas, and incubated in oxygenated Krebs-Ringer bicarbonate (KRB) buffer containing 0 or 0.35 mM Phe at 39°C for 180 min, and the samples were collected every 60 min after incubation. In PA cells, Phe increased (P < 0.05) the α-amylase secretion and mRNA expression, the phosphorylation of ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4EBP1). In PTS, the Phe increased (P < 0.05) α-amylase and trypsin synthesis, secretion and mRNA expression, as well as the phosphorylation of S6K1 and 4EBP1. Conclusively, these results suggested that Phe regulates the synthesis or secretion of α-amylase, trypsin and lipase through mRNA translation initiation factors – S6K1 and 4EBP1.

Abstract A42: Interleukin-6 induces secretion of SPINK1 and trypsin in colorectal cancer

Abstract Inflammation is known to promote colorectal cancer (CRC) tumorigenesis, but the underlying molecular mechanisms are still being uncovered. Proinflammatory cytokine interleukin-6 (IL-6) is primarily secreted by the cells of the tumor microenvironment (TME), mainly by inflammatory cells but also by activated fibroblasts. IL-6 stimulates growth and survival signaling in CRC. Inflammatory signals regulate also the production and activity of proteases and their inhibitors. Serine protease inhibitor Kazal type1 (SPINK1, aka tumor-associated trypsin inhibitor, TATI) is expressed in several tissues and over-expression of SPINK1 predicts an unfavorable outcome in many cancers, including colon cancer. The SPINK1 gene contains an IL-6 responsive element and in addition to being a protease inhibitor, it also acts as an acute phase reactant and a growth factor. Expression of serine proteases trypsin-1 and -2, the main targets of SPINK1, also correlate with malignancy and metastatic potential. The aim of this study was to assess the paracrine signaling between fibroblast-derived IL-6 and cancer cell-derived SPINK1, trypsin-1 and -2. The following expression analyses were used: quantitative PCR, immunohistochemistry, immunofluorometric assays and Western blotting. The results show that CRC cells Colo205 and HT-29 express SPINK1 and secrete it into the culture medium. IL-6 dose-dependently increased the mRNA expression and protein levels of SPINK1. Conditioned media from fibroblasts had the same effect, and conversely CRC media increased IL-6 secretion in the fibroblasts, indicating paracrine signaling between these cell types. In CRC tissues cancer cells were positive for SPINK1, while IL-6 was found in fibroblasts surrounding the cancer cells, confirming the in vitro results. In Colo205 cells the baseline levels of trypsin-1 and -2 and the respective genes PRSS1 and PRSS2 were much higher compared to HT-29 cells. In Colo205 cells IL-6 led to concomitant increase in the secretion of trypsin-1 and -2, whereas in HT-29 cells these remained constantly low. Mechanistically, addition of IL-6 led to activation of the canonical Stat3 pathway, as indicated by Stat3 phosphorylation. Stat3 inhibitor reduced both SPINK1 and trypsin-1 and -2 levels, demonstrating that Stat3 is the transcription factor driving their expression. Taken together, our results show a connection between TME-derived inflammatory response and increased SPINK1 and trypsin-1 and -2 levels. Elevated serum SPINK1 has been shown to be an independent prognostic factor in colon cancer. As SPINK1 acts as a growth factor in some cancers, it has also been suggested as a therapeutic target. Therefore assessment of SPINK1 expression and function has several potentially important clinical applications in colorectal and other cancers. The study also strengthens the role of tumor microenvironment in tumor progression and emphasizes the importance of studying tumor-stroma crosstalk of proteolytic processing. Citation Format: Kati Räsänen, Elina Lehtinen, Kristiina Nokelainen, Laura Hautala, Outi Itkonen, Ulf-Håkan Stenman, Hannu Koistinen. Interleukin-6 induces secretion of SPINK1 and trypsin in colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A42.

THE SECRETION OF DIGESTIVE ENZYMES AND CAECAL SIZE ARE DETERMINED BY DIETARY PROTEIN IN THE CRICKET Gryllus bimaculatus

In Gryllus bimaculatus, the size of the caecum decreases in the latter half of each instar to a stable minimal size with a steady minimal rate of digestive enzyme secretion until feeding resumes after ecdysis. The higher the percent protein in the newly ingested food, the faster and larger the caecum grows, and as a consequent the higher the secretion rate of trypsin and amylase. When hard boiled eggs (40% protein) are eaten the caecum is 2× larger, the trypsin secretion is almost 3× greater, and amylase 2.5× greater then when fed the same amount of apples (1.5% protein). Only dietary protein increases amylase secretion, whereas dietary carbohydrates have no effect on amylase secretion. The minimal caecal size and secretion rate must be supported by utilization of hemolymph amino acids, but the growth of the caecum and increasing enzymes secretions after the molt depend upon an amino acid source in the lumen. This simple regulation of digestive enzyme secretion is ideal for animals that must stop feeding in order to molt. This basic control system does not preclude additional regulation mechanisms, such as prandal, which is also indicated for G. bimaculatus, or even paramonal regulation.

HEAT STRESS IN POULTRY. I. DANGER, RELATED PHYSIOLOGICAL CHANGES AND SYMPTOMS (review)

Data on heat stress in poultry are surveyed in a two-part review. In the first part presented herein the authors summarized current knowledge on the influence of heat stress on alterations of metabolic and physiological processes in poultry as well as the adverse consequences for livability, growth, development and productivity, being 19.3-28.8 % less, and product quality (M.M. Mashaly et al., 2004; Sh. Imangulov et al., 2005). The level of these alterations depends on strength and durability of the exposure to stressing conditions, on age of birds, type and level of productivity, health status, nutrition program, complex of genetic factors, rearing conditions, etc. (J.O. Ayo et al., 2006; A. Kavtarashvili, T. Kolokolnikova, 2010). Heat stress triggers a wide range of behavioral, physiological and immunological alterations in poultry (J.O. Ayo et al., 2006; P.F. Surai, T.I. Fotina, 2013) as a result of intricate interactions between decreased feed consumption up to 34.7 % (M.M. Mashaly et al., 2004; Z. Abidin, A. Khatoon, 2013), disturbances of endocrine (B.Y.L. Hai et al., 2000; Y.A. Attia et al., 2009) and acid-base (S.A. Borges et al., 2004) balances, impaired antioxidant status, abnormal function of definite organs and mechanisms (P. Surai, T. Fotina, 2010). Heat stress enhances the synthesis of corticosterone, noradrenaline and adrenaline which suppress releasing and distribution of steroids and gonadotropins, thus activating deregulation mechanisms fundamental for follicular growth and development as well as the ovulation (A. Yakubu et al., 2007; Y. Song et al., 2009; A.O. Oguntunji, O.M. Alabi, 2010). Additionally, the synthesis and releasing of vitellogenin necessary for the deposition of yolk is suppressed (M. Ciftci et al., 2005). The activity and efficiency of lymphoid organs such as bursa, spleen, thymus are also impaired, the numbers of monocytes, lymphocytes and heterophils are increased (O. Altan et al., 2000; S.M. Naseem et al., 2005) resulting in impaired immune response in poultry (V. Savic et al., 1993). The antioxidant status is decreased resulting in higher levels of oxidative stress when the balance between the production of free radicals and levels of antioxidants able to neutralize them is disturbed (L.T. Kadim et al., 2008). The weight of small intestine and absorbing surface of intestinal villi are also decreased by 22-23 % and 19 %, respectively (W.G. Bottie, P.C. Harrison, 1987; M.A. Mitchell, A.J. Carlisle, 1992). The functions of thyroid, particularly synthesis of T3 hormone, and pancreas, namely secretion of trypsin, chymotrypsin and amylase, are suppressed (B.Y.L. Hai et al., 2000; Y.A. Attia et al., 2009). The acidity and bactericide activity of gastric juice and choleretic function of liver are decreased, the balance between beneficial and detrimental segments of intestinal microbial population is altered (K. Suzuki et al., 1983; J.A. Tur, R.V. Rial, 1985) while blood supply of gastrointestinal tract, especially its upper part, is inadequate (D. Wolfenson et al., 1981). Blood vessels in skin, wattles and combs are dilated (R.U. Khan et al., 2012). Attempts to maintain the thermal homeostasis result in shallow and active breathing which is 5 to 6 times more frequent in thermal stressed (panting) birds (M.K. Sabah Elkheffi et al., 2008; A.O. Oguntunji, O.M. Alabi, 2010). That leads to increased clearance of carbon dioxide necessary for synthesis of calcium carbonate for eggshell formation, followed by subsequent increase in blood pH and respiratory alkalosis, the overall disturbance of acid-base balance (R.G. Teeter et al., 1985; A.Sh. Kavtarashvili et al., 2003; S.A. Borges et al., 2004).

Some Brain Peptides Regulating the Secretion of Digestive Enzymes in the Indian Meal Moth, Plodia Interpunctella (Lepidoptera: Pyralidae)

Abstract The Indian meal moth, Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae) is a destructive polyphagous pest of many stored products. To interfere with the physiological processes, especially digestion, of the larval pest, more information on the regulatory mechanisms is needed. The brain extract from 1-day-old last instar larvae of P. interpunctella was examined. In the bioassays, the midguts were treated with the brain extract, and the carbohydrase and protease activities were measured. The brain extract showed increasing dose-dependent effects on α-amylase, α-glucosidase, β-glucosidase, α-galactosidase, β-galactosidase, and trypsin secretion in the larval midgut. The extract was further characterised and partially purified using high performance liquid chromatography (HPLC). Several peptides were determined in the brain extract regulating hydrolase activities in the larval midgut of the pest.

Editorial introductions

Current Opinion in Gastroenterology was launched in 1985. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of gastroenterology is divided into 12 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce one of the Section Editors for this issue. SECTION EDITORS Fergus ShanahanFergus ShanahanFergus Shanahan is Professor and Chairman of the Department of Medicine at University College Cork (UCC), National University of Ireland. Born and educated in Dublin, he attended medical school at University College Dublin, Ireland, where he graduated with honours in 1977. After internship and residency in internal medicine in Dublin, he did a two-year fellowship in clinical immunology at McMaster University in Ontario, Canada, followed by a two-year fellowship in gastroenterology at the University of California, Los Angeles (UCLA), USA. Following completion of his fellowship at UCLA, he was appointed to the faculty there, rising to the rank of Associate Professor before making the decision, in 1993, to return to his native Ireland. Together with colleagues from several departments and different faculties within University College Cork and Teagasc (a research agency of the Irish Ministry of Food and Agriculture), Dr Shanahan led a team of clinicians, clinician-scientists, and basic scientists to successfully compete for seed funding from Science Foundation Ireland to create a multi-disciplinary research center, the Alimentary Pharmabiotic Centre, which investigates host-microbe interactions in the gut in health and disease. Under Dr Shanahan's directorship, the center now has a membership of 168 staff, scientists, and students and has expanded its funding and research base by securing research alliances with indigenous and multinational companies within the food and pharmaceutical sectors. Dr Shanahan has published more than 450 scientific papers and several on the medical humanities and has co-edited several books. He is a Fellow of the Royal College of Physicians in Ireland, Canada, and the United Kingdom as well as of the American College of Physicians. He served as President of the Irish Society of Gastroenterology from 2007–2009. He was recently named to the “Irish Life Science 50” a list of the top 50 Irish and Irish Americans in the life science industry. His interests are in mucosal immunology, gut microbiota, inflammatory bowel disease, and most things that affect the human experience. Stephen J.D. O’KeefeStephen J.D. O’KeefeDr O’Keefe's research is in the field of nutritional gastroenterology. Most of his investigations are translational in nature, evaluating the physiological and pathophysiological responses to dietary intake and interventional feeding. He has had NIH funding for his studies on the effects of enteral and parenteral feeding on the synthesis and secretion of trypsin in humans which have formed the basis for his latest NIH funded multicenter study on distal jejunal feeding in acute pancreatitis. He has applied stable isotope labeling techniques to the study of in vivo amino acid turnover and protein synthesis, with particular attention to the measurement of mucosal protein turnover and the synthesis of trypsin in patients with acute severe pancreatitis. His second area of current interest is the management of short bowel by enteral and IV feeding, and by small bowel transplantation. Third, he is investigating the influence of diet on colonic bacterial metabolism and colon cancer risk.

Leucine markedly regulates pancreatic exocrine secretion in goats

Four goats (30.1±1.3kg) with common bile duct re-entrant catheter and duodenal catheter were used to evaluate the effects of duodenal leucine infusion on pancreatic exocrine secretion and plasma parameters with two 4×4 Latin square design experiments. In the long-term infusion experiment, goats were fed twice daily [700g/day, dry matter (DM) basis] at 8:00 and 18:00hours and were duodenally infused with 0, 3, 6, 9g/day leucine for 14days. Pancreatic juice and jugular blood samples were collected over 1-h intervals for 6h daily from d 11 to 14days to encompass a 24-h day. In the short-term experiment, goats were infused leucine for 10h continuously at the same infusion rate with Experiment 1 after feed deprivation for 24h repeated every 10days. Pancreatic juice and blood samples were collected at 0, 1, 2, 4, 6, 8 and 10h of infusion. The results showed that the long-term leucine infusion did not affect pancreatic juice secretion, protein output, trypsin and lipase secretion and plasma insulin concentration, but linearly increased α-amylase secretion. No changes in pancreatic protein and lipase secretion were observed in the short-term infusion. Pancreatic juice and α-amylase secretion responded quadratically, with the greatest values observed in the 3 and 6g/day leucine respectively. Trypsin secretion linearly decreased, while plasma insulin concentration increased linearly with increased leucine infusion. The results demonstrated that duodenal leucine infusion dose and time dependently regulated pancreatic enzyme secretion not associated with the change in plasma insulin concentration.

Value of nasojejunal nutrition in the treatment of children with acute pancreatitis

To evaluate the feasibility and effectiveness of placement of nasojejunal feeding tube and nasojejunal nutrition feeding in children with acute pancreatitis. Twenty-two patients (of whom 13 had severe acute pancreatitis and 9 acute mild pancreatitis) who needed nutritional intervention were selected. They were from Department of Gastroenterology and Surgery during the years 2009 - 2012, and they were at high nutritional risk after STONGkid nutrition risk screening. The average age of them was 5 - 15 years (9.1 years ± 2.8 years). Assisted by endoscopy, the nasojejunal feeding tube was placed in 22 of 24 patients (in 2 cases of recurrent pancreatitis the tubes were placed again after extubation). Besides the use of regular fasting, antacids, inhibitors of trypsin secretion, and anti-infective treatment, 23 cases of all children got nasojejunal nutrition treatment as well. The outcome measures included the success rate, complications of endoscope-assisted nasojejunal tube placement. The children's tolerance and nutrition indicators (weight, blood lymphocytes count, erythrocytes count, serum albumin, serum creatinine, blood urea nitrogen) were observed before and after enteral nutrition therapy. Malnutrition evaluation was done 24 times before treatment among 22 patients, incidence of malnutrition was 33% in 22 cases. Placement of nasojejunal tube placement was attempted for a total of 24 times and was successful on first placement in 22 cases, in two cases the placement was successful on the second placement, so the success rate of the first attempt for placement was 92%. No significant complications were observed in any of the cases. Twenty-three of 24 cases were given standardized enteral nutrition (one case was not given enteral nutrition therapy but underwent ERCP due to obstructive jaundice). Twenty-two of 23 cases could tolerate enteral nutrition well, only 1 case was unable to tolerate enteral nutrition due to the pancreas schizophrenia, paralytic ileus. The treatment of jejunal feeding success rate was 96%. The feeding duration was 2 - 74 d (27.0 d ± 18.3 d). The adverse reactions include plugging of the tube in two cases, constipation in two cases, five cases had abdominal pain, diarrhea in 2 cases, vomiting in 2 cases and 1 case of jejunum retention. No case had nasopharynx ulcers, gastrointestinal perforation, gastrointestinal bleeding, re-feeding syndrome and infection etc. Blood erythrocytes count, serum creatinine, blood urea nitrogen were not significantly changed. Twenty of 23 cases were cured, 2 cases were improved and 1 case was unchanged. Endoscope-assisted nasojejunal tube placement for children with acute pancreatitis is safe and feasible. Nasojejunal nutrition therapy is effective for acute pancreatitis patients who are at severe nutritional risk, especially for the improvement of the nutritional status of children.

Environmental control of trypsin secretion in the midgut of the two-spotted field cricket, Gryllus bimaculatus

The two most important environmental factors controlling the release of trypsin in Gryllus bimaculatus are temperature and food consumption. Food consumption is in turn controlled by food availability (quantity), food quality (contained nutrients, inhibitors), developmental stage, age, sex and the daily light–dark cycle. The secretion of trypsin was higher at an acclimation temperature (AT) of 22°C than at 32°C, although the weight of caecal tissue and body weight were lower. The trypsin secretion at both experimental temperatures (25°C and 35°C) was almost 2 times greater in crickets maintained at 22°C AT since egg hatch than those maintained only since the last larval stage, but not at 32°C AT. Acclimation became increasingly rotational with increased exposure time at different rearing temperatures. The more food consumed the higher the trypsin secretion. Secretion was highest on day 3 in adult females and day 2 in males, corresponding to the day of maximal food consumption. Secretion was less than 20% in starved or cellulose fed females compared to those fed a control diet. Food reached the caeca in starved crickets within 30min and induced an increased trypsin secretion. Crickets started feeding at the onset of darkness, and trypsin secretion was significantly elevated near the end of the scotophase. The in vivo response to 0.4% soybean trypsin inhibitor (SBTI) fed throughout the last larval stage resulted in reduced growth and a 50% decrease in trypsin secretion in 2day old adult females. An adaptation to the reduction of trypsin secretion occurred when G. bimaculatus was fed 0.1% and 0.2% SBTI, but not when fed with 0.4%.

Regulation of pancreatic exocrine secretion in goats: differential effects of short‐ and long‐term duodenal phenylalanine treatment

Four yearling goats (31.2 ± 2.5 kg), surgically fitted with common bile duct reentrant and duodenal catheter, were used in two 4 × 4 Latin square design experiments to investigate the effects of duodenal infusion of phenylalanine for different times on pancreatic exocrine secretion (PES). In experiment 1 (the long-term experiment), goats were duodenally infused with 0, 2, 4 or 8 g/day phenylalanine for 14 day. Pancreatic juice and jugular blood samples were collected over 1-h intervals for 6 h daily from day 11 to day 14 to encompass a 24-h day. In experiment 2 (the short-term experiment), goats were infused with phenylalanine for 10 h continuously at the same infusion rate as experiment 1 after feed deprivation for 24 h repeated every 10 day. Pancreatic juice and blood samples were collected at 0, 1, 2, 4, 6, 8 and 10 h of infusion. The volume and pH of pancreatic juice were measured, and a 5% subsample was composited and frozen until analysis of enzyme activities. Plasma was frozen until analysis of insulin and cholecystokinin (CCK). In experiment 1, pancreatic juice, α-amylase secretion and plasma CCK concentration responded quadratically (p < 0.05), with the top value observed at the 2 g/day phenylalanine. Trypsin secretion had a quadratic response (p < 0.05), with secretion increasing up to 4 g/day phenylalanine and decreasing thereafter. Phenylalanine linearly decreased pancreatic protein and lipase secretion (p < 0.05). The results of correlation analysis showed significant correlations (p < 0.05) between plasma CCK concentration and secretion of α-amylase and trypsin. However, the short-term phenylalanine infusion did not influence (p > 0.05) pancreatic juice, protein, α-amylase, lipase, trypsin secretion and plasma CCK concentration. These results indicate PES of ruminants is stimulated by phenylalanine and is potentially mediated by CCK in the long-term duodenal infusion treatment, but is not influenced by phenylalanine in the short-term duodenal infusion treatment.

Dietary protein quality differentially regulates trypsin enzymes at the secretion and transcription level in Panulirus argus by distinct signaling pathways

The effects of pelleted diets with different protein composition (fish, squid or soybean meals as main protein sources) on trypsin secretion and expression were studied in the lobster Panulirus argus. Trypsin secretion was shown to be maximal 4 h after ingestion. At this time, fish- and squid-based diets induced trypsin secretion, as well as up-regulation of the major trypsin isoform at the transcription level. While fish- and squid-based diets elicited a prandial response, soybean-based diet failed to stimulate the digestive gland to secrete trypsin into the gastric fluid or induce trypsin expression above the levels observed in fasting lobsters. In vitro assays showed that intact proteins rather than protein hydrolysates stimulate trypsin secretion in the lobster. However, the signal for trypsin transcription appears to be different to that for secretion and is probably mediated by the appearance of free amino acids in the digestive gland, suggesting a stepwise regulation of trypsin enzymes during digestion. We conclude that trypsin enzymes in P. argus are regulated at the transcription and secretion level by the quality of dietary proteins through two distinct signaling pathways. Our results indicate that protein digestion efficiency in spiny lobsters can be improved by selecting appropriated protein sources. However, other factors like the poor solubility of dietary proteins in dry diets could hamper further enhancement of digestion efficiency.