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Sample records for pancreatic function test

  1. Tests of pancreatic exocrine function - clinical significance in pancreatic and non-pancreatic disorders.

    PubMed

    Keller, Jutta; Aghdassi, Ali Alexander; Lerch, Markus M; Mayerle, Julia V; Layer, Peter

    2009-01-01

    The pancreas functions as the main factory for digestive enzymes and therefore enables food utilisation. Pancreatic exocrine insufficiency, partial or complete loss of digestive enzyme synthesis, occurs primarily in disorders directly affecting pancreatic tissue integrity. However, other disorders of the gastrointestinal tract, such as coeliac disease, inflammatory bowel disease, Zollinger-Ellison syndrome or gastric resection can either mimic or cause pancreatic exocrine insufficiency. The overt clinical symptoms of pancreatic exocrine insufficiency are steatorrhoea and maldigestion, which frequently become apparent in advanced stages. Several direct and indirect function tests are available for assessment of pancreatic function but until today diagnosis of excretory insufficiency is difficult as in mild impairment clinically available function tests show limitations of diagnostic accuracy. This review focuses on diagnosis of pancreatic exocrine insufficiency in pancreatic and non-pancreatic disorders. PMID:19505669

  2. Cholesteryl octanoate breath test. Preliminary studies on a new noninvasive test of human pancreatic exocrine function.

    PubMed

    Cole, S G; Rossi, S; Stern, A; Hofmann, A F

    1987-12-01

    A new breath test for noninvasive assessment of pancreatic exocrine function in humans was developed. The test is based on the hydrolysis of cholesteryl-[1-14C]octanoate by pancreatic carboxyl ester lipase (cholesterol esterase) with subsequent absorption and hepatic metabolism of the liberated octanoate to 14CO2. The rate at which 14CO2 appears in breath appeared to be proportional to the rate of hydrolysis. The substrate is administered as a gum acacia stabilized emulsion of vegetable oil (18 g) containing cholesteryl octanoate (2 g; 4.4 microCi) dispersed in a 500-ml isotonic meal. Tests were performed in 6 healthy volunteers and 11 patients with pancreatic disease with varying degrees of steatorrhea. In healthy subjects, 14CO2 output was rapid with peak output occurring at 60-90 min in all subjects; cumulative output in 4 h averaged 30%. Duplicate studies indicated that the time-course of 14CO2 recovery was reproducible. The pattern of 14CO2 output in patients with pancreatic disease varied widely. Patients without steatorrhea (fecal fat less than or equal to 7 g/day) or with mild steatorrhea (fecal fat 7-11 g/day) had normal or near normal patterns of 14CO2 output, whereas patients with moderate or severe steatorrhea (fecal fat greater than 11 g/day) expired 14CO2 at a rate one-third to one-tenth that of the healthy volunteers. Addition of pancreatic enzyme supplementation to the test meal increased 14CO2 output in 6 of 6 patients with moderate or severe steatorrhea, suggesting that the activity of pancreatic carboxyl ester lipase was rate limiting in these patients. In an additional study in a healthy volunteer, 14CO2 and 13CO2 were measured simultaneously in breath after ingestion of a test meal containing cholesteryl-[1-13C]octanoate and 14C-octanoate. 14CO2 was expired more rapidly than 13CO2, suggesting that hydrolysis of the substrate may also be rate limiting in healthy volunteers. These studies indicate that severe pancreatic exocrine dysfunction can

  3. Exocrine and endocrine functional reserve in the course of chronic pancreatitis as studied by maximal stimulation tests.

    PubMed

    Cavallini, G; Bovo, P; Zamboni, M; Bosello, O; Filippini, M; Riela, A; Brocco, G; Rossi, L; Pelle, C; Chiavenato, A

    1992-01-01

    Thirty patients suffering from chronic alcoholic pancreatitis (18 calcified) were entered into a study of exocrine and endocrine pancreatic function based on two maximal stimulation tests, namely the secretin-cerulein test and the glucagon test with serum assays of C peptide. The glucagon test was also performed in 19 control subjects. In addition, 10 chronic pancreatitis patients and nine controls were subjected to an oral glucose tolerance test (OGTT) with serum insulin determinations. C peptide basal values were decreased only in patients with severe pancreatic exocrine insufficiency (P less than 0.001), while delta C peptide values were also reduced in patients with moderate exocrine insufficiency (P less than 0.001). Lipase output correlated very well with delta C peptide values (P less than 0.001). While serum insulin levels during OGTT and C peptide basal values showed no significant differences between the chronic pancreatitis and control groups, delta C peptide values were significantly reduced in chronic pancreatitis patients (P less than 0.02). Both endocrine and exocrine function are impaired in chronic pancreatitis, as demonstrated by maximal tests, even in early stages of the disease. PMID:1728534

  4. ESPGHAN and NASPGHAN Report on the Assessment of Exocrine Pancreatic Function and Pancreatitis in Children.

    PubMed

    Taylor, Christopher J; Chen, Kathy; Horvath, Karoly; Hughes, David; Lowe, Mark E; Mehta, Devendra; Orabi, Abrahim I; Screws, Jeremy; Thomson, Mike; Van Biervliet, Stephanie; Verkade, Henkjan J; Husain, Sohail Z; Wilschanski, Michael

    2015-07-01

    The purpose of this clinical report is to discuss several recent advances in assessing exocrine pancreatic insufficiency (EPI) and pancreatitis in children, to review the array of pancreatic function tests, to provide an update on the inherited causes of EPI, with special emphasis on newly available genetic testing, and to review newer methods for evaluating pancreatitis. PMID:25915425

  5. Blood tests for acute pancreatitis

    PubMed Central

    Basnayake, Chamara; Ratnam, Dilip

    2015-01-01

    Summary The diagnosis of acute pancreatitis requires the presence of at least two of the three diagnostic criteria – characteristic abdominal pain, elevated serum amylase or lipase, and radiological evidence of pancreatitis. Serum concentrations of amylase and lipase rise within hours of the pancreatic injury. A threshold concentration 2–4 times the upper limit of normal is recommended for diagnosis. Serum lipase is now the preferred test due to its improved sensitivity, particularly in alcohol-induced pancreatitis. Its prolonged elevation creates a wider diagnostic window than amylase. Neither enzyme is useful in monitoring or predicting the severity of an episode of pancreatitis in adults. New biomarkers including trypsinogen and elastase have no significant advantage over amylase or lipase. PMID:26648641

  6. Tests for Pancreatic Cancer

    MedlinePlus

    ... be useful if the surgeon is concerned the cancer has spread beyond the pancreas and wants to look at (and possibly biopsy) ... on someone who has a tumor in the pancreas if imaging tests show the tumor is very likely to be cancer and if it looks like surgery can remove ...

  7. Evaluation of two forms of N-benzoyl-L-tyrosyl p-aminobenzoic acid in pancreatic function testing of dogs.

    PubMed

    Burrows, C F; Orfely, C

    1989-01-01

    Plasma para-aminobenzoic acid (PABA) concentrations were compared in 12 dogs after oral administration of either a powdered suspension or a solution of N-benzoyl-L-tyrosyl-PABA. Peak PABA plasma concentrations were significantly higher at 30, 60 and 90 minutes after administration of the solution (P less than 0.05). As the solution may now be used as a clinical test, interpretation of the results by comparison with normal absorption curves obtained after administration of the suspension could contribute to a failure to diagnose canine exocrine pancreatic insufficiency. PMID:2784215

  8. Sensitivity and specificity of an abbreviated 13C-mixed triglyceride breath test for measurement of pancreatic exocrine function

    PubMed Central

    Meier, Viola; Wolfram, Kristina U; Rosien, Ulrich; Layer, Peter

    2014-01-01

    Background A modified 13C-mixed triglyceride breath test (13C -MTGT) detects moderate pancreatic exocrine insufficiency noninvasively and reliably, but it requires prolonged breath sampling (6 hours (hr)). Objective We aimed to investigate whether 13C -MTGT can be abbreviated, to optimize clinical usability. Methods We analyzed the 13C-MTGT of 200 consecutive patients, retrospectively. Cumulative 1–5 hr 13C-exhalation values were compared with the standard parameter (6-hr cumulative 13C-exhalation). We determined the sensitivity and specificity of shortened breath sampling periods, by comparison with the normal values from 10 healthy volunteers, whom also underwent a secretin test to quantitate pancreatic secretion. Moreover, we evaluated the influence of gastric emptying (GE), using a 13C-octanoic acid breath test in a subset (N = 117). Results The 1–5 hr cumulative 13C-exhalation tests correlated highly and significantly with the standard parameter (p < 0.0001). Sensitivity for detection of impaired lipolysis was high (≥77%), but the specificity was low (≥38%) for the early measurements. Both parameters were high after 4 hrs (88% and 94%, respectively) and 5 hrs (98% and 91%, respectively). Multivariate linear correlation analysis confirmed that GE strongly influenced early postprandial 13C-exhalation during the 13C-MTGT. Conclusion Shortening of the 13C -MTGT from 6 to 4 hrs of duration was associated with similar diagnostic accuracy, yet increased clinical usability. The influence of GE on early postprandial results of the 13C-MTGT precluded further abbreviation of the test. PMID:25083286

  9. Genetics and Genetic Testing in Pancreatic Cancer.

    PubMed

    Whitcomb, David C; Shelton, Celeste A; Brand, Randall E

    2015-10-01

    Genetic testing of germline DNA is used in patients suspected of being at risk of pancreatic ductal adenocarcinoma (PDAC) to better define the individual's risk and to determine the mechanism of risk. A high genetic risk increases the pretest probability that a biomarker of early cancer is a true positive and warrants further investigation. The highest PDAC risk is generally associated with a hereditary predisposition. However, the majority of PDAC results from complex, progressive gene-environment interactions that currently fall outside the traditional risk models. Over many years, the combination of inflammation, exposure to DNA-damaging toxins, and failed DNA repair promote the accumulation of somatic mutations in pancreatic cells; PDAC risk is further increased by already present oncogenic germline mutations. Predictive models and new technologies are needed to classify patients into more accurate and mechanistic PDAC risk categories that can be linked to improved surveillance and preventative strategies. PMID:26255042

  10. 13C-egg white breath test: a non-invasive test of pancreatic trypsin activity in the small intestine

    PubMed Central

    Evenepoel, P; Hiele, M; Geypens, B; Geboes, K; Rutgeerts, P; Ghoos, Y

    2000-01-01

    BACKGROUND—The recent availability of egg white protein highly enriched with 13C has allowed breath test technology to be adapted for the study of protein digestion and absorption. Pancreatic trypsin is considered to be the key enzyme in the proteolytic cascade.
AIM—To evaluate trypsin activity in the small intestine of healthy volunteers and patients with pancreatic disease by a recently developed 13C-egg white breath test.
METHODS—A total of 48 healthy volunteers and 30 patients with pancreatic disease were studied after ingestion of a test meal consisting of 22 g 13C-labelled egg protein. Breath samples were taken before and after ingestion of the meal and analysed for 13CO2 concentration. Moreover, pancreatic trypsin output after maximal stimulation was measured in 13 patients and nine healthy volunteers.
RESULTS—The six hour cumulative 13CO2 excretion in breath was significantly lower in patients than controls (mean (SEM): 6.23 (0.82)% v 19.16 (0.58)%, p<0.0001). An excellent correlation was found between the six hour cumulative 13CO2 excretion and trypsin activity after maximal pancreatic stimulation.
CONCLUSION—The non-invasive 13C-egg white breath test is promising as an indirect pancreatic proteolytic function test.


Keywords: breath test; pancreatic disease; trypsin; protein; assimilation PMID:10601055

  11. Clock genes, pancreatic function, and diabetes.

    PubMed

    Vieira, Elaine; Burris, Thomas P; Quesada, Ivan

    2014-12-01

    Circadian physiology is responsible for the temporal regulation of metabolism to optimize energy homeostasis throughout the day. Disturbances in the light/dark cycle, sleep/wake schedule, or feeding/activity behavior can affect the circadian function of the clocks located in the brain and peripheral tissues. These alterations have been associated with impaired glucose tolerance and type 2 diabetes. Animal models with molecular manipulation of clock genes and genetic studies in humans also support these links. It has been demonstrated that the endocrine pancreas has an intrinsic self-sustained clock, and recent studies have revealed an important role of clock genes in pancreatic β cells, glucose homeostasis, and diabetes. PMID:25457619

  12. 13C labelled cholesteryl octanoate breath test for assessing pancreatic exocrine insufficiency

    PubMed Central

    Ventrucci, M; Cipolla, A; Ubalducci, G; Roda, A; Roda, E

    1998-01-01

    Background—A non-invasive test for assessment of fat digestion has been developed based on the intraluminal hydrolysis of cholesteryl-[1-13C]octanoate by pancreatic esterase. 
Aims—To determine the diagnostic performance of this breath test in the assessment of exocrine pancreatic function. 
Methods—The test was performed in 20 healthy controls, 22 patients with chronic pancreatic disease (CPD), four with biliopancreatic diversion (BPD), and 32 with non-pancreatic digestive diseases (NPD); results were compared with those of other tubeless tests (faecal chymotrypsin and fluorescein dilaurate test). 
Results—Hourly recoveries of 13CO2 were significantly lower in CPD when compared with healthy controls or NPD. In patients with CPD with mild to moderate insufficiency, the curve of 13CO2 recovery was similar to that of healthy controls, while in those with severe insufficiency it was flat. In three patients with CPD with severe steatorrhoea, a repeat test after pancreatic enzyme supplementation showed a significant rise in 13CO2 recovery. The four BPD patients had low and delayed 13CO2 recovery. Only eight of the 32 patients with NPD had abnormal breath test results. There was a significant correlation between the results of the breath test and those of faecal chymotrypsin, the fluorescein dilaurate test, and faecal fat measurements. For the diagnosis of pancreatic disease using the three hour cumulative 13CO2 recovery test, the sensitivity was 68.2% and specificity 75.0%; values were similar to those of the other two tubeless pancreatic function tests. In seven healthy controls, nine patients with CPD, and nine with NPD a second breath test was performed using Na-[1-13C]octanoate and a pancreatic function index was calculated as the ratio of 13C recovery obtained in the two tests: at three hours this index was abnormal in eight patients with CPD and in three with NPD. 
Conclusion—The cholesteryl-[1-13C]octanoate breath test can be useful for the

  13. Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis.

    PubMed

    Jin, Yuepeng; Bai, Yongyu; Li, Qiang; Bhugul, Pravin Avinash; Huang, Xince; Liu, Lewei; Pan, Liangliang; Ni, Haizhen; Chen, Bicheng; Sun, Hongwei; Zhang, Qiyu; Hehir, Michael; Zhou, Mengtao

    2016-01-01

    The aim of the present study was to investigate the pancreatic exocrine function in a canine model and to analyze the changes in organelles of pancreatic acinar cells during the early stage of acute pancreatitis (AP). AP was induced by retrograde injection of 5% sodium taurocholate (0.5 ml/kg) into the main pancreatic duct of dogs. The induction of AP resulted in serum hyperamylasemia and a marked reduction of amylase activity in the pancreatic fluid (PF). The pancreatic exocrine function was markedly decreased in subjects with AP compared with the control group. After the induction of AP, histological examination showed acinar cell edema, cytoplasmic vacuolization, fibroblasts infiltration, and inflammatory cell infiltration in the interstitium. Electron micrographs after the induction of AP revealed that most of the rough endoplasmic reticulum (RER) were dilated and that some of the ribosomes were no longer located on the RER. The mitochondria were swollen, with shortened and broken cristae. The present study demonstrated, in a canine model, a reduced volume of PF secretion with decreased enzyme secretion during the early stage of AP. Injury of mitochondria and dilatation and degranulation of RER may be responsible for the reduced exocrine function in AP. Furthermore, the present model and results may be useful for researching novel therapeutic measures in AP. PMID:26895040

  14. Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis

    PubMed Central

    Li, Qiang; Bhugul, Pravin Avinash; Huang, Xince; Liu, Lewei; Pan, Liangliang; Ni, Haizhen; Chen, Bicheng; Sun, Hongwei; Zhang, Qiyu; Hehir, Michael; Zhou, Mengtao

    2016-01-01

    The aim of the present study was to investigate the pancreatic exocrine function in a canine model and to analyze the changes in organelles of pancreatic acinar cells during the early stage of acute pancreatitis (AP). AP was induced by retrograde injection of 5% sodium taurocholate (0.5 ml/kg) into the main pancreatic duct of dogs. The induction of AP resulted in serum hyperamylasemia and a marked reduction of amylase activity in the pancreatic fluid (PF). The pancreatic exocrine function was markedly decreased in subjects with AP compared with the control group. After the induction of AP, histological examination showed acinar cell edema, cytoplasmic vacuolization, fibroblasts infiltration, and inflammatory cell infiltration in the interstitium. Electron micrographs after the induction of AP revealed that most of the rough endoplasmic reticulum (RER) were dilated and that some of the ribosomes were no longer located on the RER. The mitochondria were swollen, with shortened and broken cristae. The present study demonstrated, in a canine model, a reduced volume of PF secretion with decreased enzyme secretion during the early stage of AP. Injury of mitochondria and dilatation and degranulation of RER may be responsible for the reduced exocrine function in AP. Furthermore, the present model and results may be useful for researching novel therapeutic measures in AP. PMID:26895040

  15. Procalcitonin Strip Test as an Independent Predictor in Acute Pancreatitis.

    PubMed

    Dias, Brendan Hermenigildo; Rozario, Anthony Prakash; Olakkengil, Santosh Antony; V, Anirudh

    2015-12-01

    Plasma procalcitonin (PCT) is a highly specific marker for the diagnosis of bacterial infection and sepsis. Studies have demonstrated its role in the setting of sepsis and acute pancreatitis. This study aims to analyze and compare the prognostic efficacy of plasma procalcitonin strip test in acute pancreatitis. A prospective study was conducted in the department of general surgery from June 2012 to June 2013. Plasma procalcitonin was estimated by the semiquantitative strip test. The study included a total of 50 patients diagnosed to have acute pancreatitis. Data was collected and statistically analyzed using SPSS version 17. Thirty-nine out of the 50 patients (78 %) were males with a mean age of 46.8 years (range, 25-78 years) and 25 patients (50 %) had ethanol-induced pancreatitis, while 13 patients (26 %) had gall stone pancreatitis. Plasma PCT values were found to correlate better than CRP levels and total leukocyte count with the total duration of hospitalization, ITU, and ICU stay, as well as with the progression to severe acute pancreatitis. A cut off for plasma PCT of >2 ng/mL was found to be 100 % sensitive and 100 % specific and a cut off for CRP of >19 mg/dL was 70 % sensitive and 65 % specific for predicting the progression to severe acute pancreatitis. Plasma PCT also correlated well with antibiotic requirement. A cut off value of >0.5 ng/mL for plasma PCT was 100 % sensitive and 80 % specific and a cut off value of >18 mg/dL for CRP was 86 % sensitive and 63 % specific for predicting antibiotic requirement. Plasma procalcitonin is an early and reliable prognostic indicator in acute pancreatitis. The procalcitonin strip test is a rapid test which is useful in analyzing prognosis in patients with acute pancreatitis. PMID:27011501

  16. Pancreatic functions in high salt fed female rats

    PubMed Central

    Lasheen, Noha N

    2015-01-01

    Salt consumption has been increased worldwide and the association of high salt diets with enhanced inflammation and target organ damage was reported. Little data were available about the effect of high salt diet on exocrine function of pancreas, while the relation between high salt intake and insulin sensitivity was controversial. This study was designed to investigate the effect of high salt diet on exocrine and endocrine pancreatic functions, and to elucidate the possible underlying mechanism(s). Twenty adult female Wistar rats were randomly divided into two groups; control group; fed standard rodent diet containing 0.3% NaCl, and high salt fed group; fed 8% NaCl for 8 weeks. On the day of sacrifice, rats were anesthized by i.p. pentobarbitone (40 μg/kg B.W.). Nasoanal length was measured and fasting blood glucose was determined from rat tail. Blood samples were obtained from abdominal aorta for determination of plasma sodium, potassium, amylase, lipase, aldosterone, insulin, transforming growth factor-β (TGF-β1), and interleukin 6 (IL6). Pancreata of both groups were histologically studied. Compared to control group, 8-week high salt fed group showed: significant elevation in body weight, body mass index, Lee index, plasma sodium, TGF-β1 and IL6, however, plasma aldosterone, amylase, lipase, and insulin levels were significantly decreased. A nonsignificant increase in plasma potassium and nonsignificant changes in fasting blood glucose and HOMA-IR were detected between groups. Pancreatic fibrosis was observed in test group. High salt diet for 8 weeks caused pancreatic fibrosis evidenced by decline of both exocrine and endocrine functions of pancreas in Wistar rats. PMID:26216433

  17. Mesobiliverdin IXα Enhances Rat Pancreatic Islet Yield and Function.

    PubMed

    Ito, Taihei; Chen, Dong; Chang, Cheng-Wei Tom; Kenmochi, Takashi; Saito, Tomonori; Suzuki, Satoshi; Takemoto, Jon Y

    2013-01-01

    The aims of this study were to produce mesobiliverdin IXα, an analog of anti-inflammatory biliverdin IXα, and to test its ability to enhance rat pancreatic islet yield for allograft transplantation into diabetic recipients. Mesobiliverdin IXα was synthesized from phycocyanobilin derived from cyanobacteria, and its identity and purity were analyzed by chromatographic and spectroscopic methods. Mesobiliverdin IXα was a substrate for human NADPH biliverdin reductase. Excised Lewis rat pancreata infused with mesobiliverdin IXα and biliverdin IXα-HCl (1-100 μM) yielded islet equivalents as high as 86.7 and 36.5%, respectively, above those from non-treated controls, and the islets showed a high degree of viability based on dithizone staining. When transplanted into livers of streptozotocin-induced diabetic rats, islets from pancreata infused with mesobiliverdin IXα lowered non-fasting blood glucose (BG) levels in 55.6% of the recipients and in 22.2% of control recipients. In intravenous glucose tolerance tests, fasting BG levels of 56 post-operative day recipients with islets from mesobiliverdin IXα infused pancreata were lower than those for controls and showed responses that indicate recovery of insulin-dependent function. In conclusion, mesobiliverdin IXα infusion of pancreata enhanced yields of functional islets capable of reversing insulin dysfunction in diabetic recipients. Since its production is scalable, mesobiliverdin IXα has clinical potential as a protectant of pancreatic islets for allograft transplantation. PMID:23630498

  18. Endocrine function after immunosuppression of pancreatic allograft by ionizing irradiation in the primate

    SciTech Connect

    Du Toit, D.F.; Heydenrych, J.J.; Smit, B.; Louw, G.; Zuurmond, T.; Laker, L.; Els, D.; Weideman, A.; Wolfe-Coote, S.; Du Toit, L.B.

    1986-05-01

    The object of this preliminary study was to evaluate the endocrine function after heterotopic intraperitoneal segmental pancreatic allotransplantation with unligated duct in irradiated, totally pancreatectomized primates. All allograft recipients received, pre- and peroperative donor-specific blood transfusions and peroperative external irradiation from a linear accelerator; 200 rads was administered weekly and increased to a total dose of 1,500 rads. Pancreatic transplantation was performed between 2 and 6 weeks after completion of irradiation and preoperative blood transfusions. As previously reported, only minimal pancreatic allograft survival was achieved following preoperative irradiation. One recipient remained normoglycaemic for greater than 100 days after transplantation, the longest surviving pancreatic allograft recipient reported from this laboratory. Intravenous glucose tolerance test results in this recipient revealed normoglycaemia, reduced K-value, hypoinsulinaemia, normal glucagon response, reduced C-peptide values, and moderate glucose intolerance. Aortography and electron-microscopic examination of allograft biopsy tissue confirmed the presence of a functioning allograft.

  19. [Standard and Augmented Secretin Tests in Chronic Pancreatitis].

    PubMed

    Bordalo, O; Noronha, M; Lamy, J; Dreiling, D

    1976-03-26

    The response of the pancreas to standard (1.0 U/kg) and augmented (4.0-5.0 U/kg) doses of secretin was compared in normal subjects and patients. The results of the investigation showed that for clinical purposes the standard test is sufficient for the diagnosis of pancreatic diseases causing gross destruction of the parenchyma. The augmented test is of particular value when the response to 1 U/kg produces equivocal results, since greater stimulation enhances the masked secretory deficiency. The effect of the augmented stimulus in alcoholic patients suggests the hypothesis that the post-secretin response pattern of minimal pancreatic inflammatory disease is hypersecretion. Repeated observation is alcoholic hypersecretors has provided data which can explain the evolution of pancreatic pathology in the terminal stages of chronic pancreatitis. PMID:817172

  20. Stereotypical Metabolic Response to Endoscopic Retrograde Cholangiopancreatography Show Alterations in Pancreatic Function Regardless of Post-Procedure Pancreatitis

    PubMed Central

    Lusczek, Elizabeth R; Colling, Kristen; Muratore, Sydne; Conwell, Darwin; Freeman, Martin; Beilman, Greg

    2016-01-01

    ERCP-induced AP. Aspartate and asparagine were identified as well-connected hubs in post-ERCP serum networks of cases and were correlated with aspartate transaminase (AST) and white blood cell count levels. These features were not evident in controls. Serum aspartate was elevated in AP patients relative to those without AP after ERCP (P=0.03). CONCLUSIONS: In this pilot study, ERCP was found to induce global changes in urine and serum metabolomes indicative of alterations in pancreatic function and insulin resistance. This should be taken into consideration in future research on this topic. Post-ERCP serum metabolic networks indicate functional differences surrounding aspartate metabolism between patients with AP and those without. Further study must be done in larger patient populations to test elevated lipase as a prognostic biomarker associated with risk of developing AP and to examine active metabolic mechanisms at work. PMID:27148850

  1. Chronic Pancreatitis

    PubMed Central

    DiMagno, Matthew J.; DiMagno, Eugene P.

    2012-01-01

    Purpose of review We review important new clinical observations in chronic pancreatitis (CP) made in the past year. Recent findings Tropical pancreatitis associates with SPINK1 and/or CFTR gene mutations in approximately 50% of patients, similar to the frequency in idiopathic CP. Corticosteroids increase secretin-stimulated pancreatic bicarbonate concentrations in AIP by restoring mislocalized CFTR protein to the apical ductal membrane. Most patients with asymptomatic hyperenzymemia have pancreatic lesions of unclear significance or no pancreatic lesions. Common pitfalls in the use of diagnostic tests for EPI confound interpretation of findings in IBS and severe renal insufficiency. Further study is needed to improve the accuracy of endoscopic ultrasonography (EUS) to diagnose CP. Celiac plexus block provides short term pain relief in a subset of patients. Summary Results of this year’s investigations further elucidated the genetic associations of tropical pancreatitis, a reversible mislocalization of ductal CFTR in AIP, the association of asymptomatic pancreatic hyperenzymemia with pancreatic disorders, limitations of diagnostic tests for EPI, diagnosis of CP by EUS and endoscopic pancreatic function testing and treatment of pain. PMID:21844753

  2. Uncovering Factors Related to Pancreatic Beta-Cell Function

    PubMed Central

    Curran, Aoife M.; Ryan, Miriam F.; Drummond, Elaine; Gibney, Eileen R.; Gibney, Michael J.; Roche, Helen M.; Brennan, Lorraine

    2016-01-01

    Aim The incidence of type 2 diabetes has increased rapidly on a global scale. Beta-cell dysfunction contributes to the overall pathogenesis of type 2 diabetes. However, factors contributing to beta-cell function are not clear. The aims of this study were (i) to identify factors related to pancreatic beta-cell function and (ii) to perform mechanistic studies in vitro. Methods Three specific measures of beta-cell function were assessed for 110 participants who completed an oral glucose tolerance test as part of the Metabolic Challenge Study. Anthropometric and biochemical parameters were assessed as potential modulators of beta-cell function. Subsequent in vitro experiments were performed using the BRIN-BD11 pancreatic beta-cell line. Validation of findings were performed in a second human cohort. Results Waist-to-hip ratio was the strongest anthropometric modulator of beta-cell function, with beta-coefficients of -0.33 (p = 0.001) and -0.30 (p = 0.002) for beta-cell function/homeostatic model assessment of insulin resistance (HOMA-IR), and disposition index respectively. Additionally, the resistin-to-adiponectin ratio (RA index) emerged as being strongly associated with beta-cell function, with beta-coefficients of -0.24 (p = 0.038) and -0.25 (p = 0.028) for beta-cell function/HOMA-IR, and disposition index respectively. Similar results were obtained using a third measure for beta-cell function. In vitro experiments revealed that the RA index was a potent regulator of acute insulin secretion where a high RA index (20ng ml-1 resistin, 5nmol l-1 g-adiponectin) significantly decreased insulin secretion whereas a low RA index (10ng ml-1 resistin, 10nmol l-1 g-adiponectin) significantly increased insulin secretion. The RA index was successfully validated in a second human cohort with beta-coefficients of -0.40 (p = 0.006) and -0.38 (p = 0.008) for beta-cell function/ HOMA-IR, and disposition index respectively. Conclusions Waist-to-hip ratio and RA index were identified

  3. Pancreatitis

    MedlinePlus

    ... the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is ...

  4. 62Zn-EDDA: a radiopharmaceutical for pancreatic functional diagnosis.

    PubMed

    Fujibayashi, Y; Saji, H; Yomoda, I; Kawai, K; Horiuchi, K; Adachi, H; Torizuka, K; Yokoyama, A

    1986-01-01

    As Zn is closely associated with the exocrine and endocrine functions of the pancreas, exploitation of Zn metabolism for anatomical and functional diagnosis was conceived, namely with the recent availability of positron emitting 62Zn (t1/2 = 9 h). In the present paper, response changes in Zn biodistribution (mice) and Zn excretion through the pancreatic duct (rats) due to the stimulation of gastro-intestinal hormones like secretin, CCK-PZ (exocrine stimulation) and glucose (endocrine stimulation) were studied. Under these stimuli, the pancreatic secretion of radioactive Zn through cannulated pancreatic duct showed increased Zn secretion only under the CCK-PZ effect, 3 h post 65Zn (t1/2 = 270 d) injection. Tissue biodistribution in mice pre-injected with 65Zn showed pancreas specific decrease of radioactive Zn whenever a gastro-intestinal hormone was post-administered, whereas the glucose effect was negligible. Thus, the effective mobilization of the injected radioactive Zn, upon exocrine stimulation, represented by CCK-PZ, favored the exploration of a functional study of the pancreas with the positron computed tomograph (PCT) using short lived nuclide labeled 62Zn-EDDA in dog. Evidence of the applicability of this system in regional function studies of the pancreas was obtained. Demonstration of Zn participation in the exocrine function of the pancreas in-vivo holds considerable promise for diagnosis of pancreatic diseases. PMID:3086246

  5. Quantitative Sensory Testing Predicts Pregabalin Efficacy in Painful Chronic Pancreatitis

    PubMed Central

    Olesen, Søren S.; Graversen, Carina; Bouwense, Stefan A. W.; van Goor, Harry; Wilder-Smith, Oliver H. G.; Drewes, Asbjørn M.

    2013-01-01

    Background A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis. Methods Sixty-four patients with painful chronic pancreatitis received pregabalin (150–300 mg BID) or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area) and C5 (control area). To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio). Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy. Results The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9–1.3)) compared to non-responders group (ePDT ratio: 1.6 (1.5–2.0)) (P = 0.001). The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (P = 0.007). The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy. Conclusions The present study provides first evidence that quantitative sensory testing predicts the analgesic effect of pregabalin in patients with painful chronic pancreatitis. The method can be used to tailor pain medication based on patient’s individual sensory profile and thus

  6. MicroRNA-7a regulates pancreatic β cell function

    PubMed Central

    Latreille, Mathieu; Hausser, Jean; Stützer, Ina; Zhang, Quan; Hastoy, Benoit; Gargani, Sofia; Kerr-Conte, Julie; Pattou, Francois; Zavolan, Mihaela; Esguerra, Jonathan L.S.; Eliasson, Lena; Rülicke, Thomas; Rorsman, Patrik; Stoffel, Markus

    2014-01-01

    Dysfunctional microRNA (miRNA) networks contribute to inappropriate responses following pathological stress and are the underlying cause of several disease conditions. In pancreatic β cells, miRNAs have been largely unstudied and little is known about how specific miRNAs regulate glucose-stimulated insulin secretion (GSIS) or impact the adaptation of β cell function to metabolic stress. In this study, we determined that miR-7 is a negative regulator of GSIS in β cells. Using Mir7a2 deficient mice, we revealed that miR-7a2 regulates β cell function by directly regulating genes that control late stages of insulin granule fusion with the plasma membrane and ternary SNARE complex activity. Transgenic mice overexpressing miR-7a in β cells developed diabetes due to impaired insulin secretion and β cell dedifferentiation. Interestingly, perturbation of miR-7a expression in β cells did not affect proliferation and apoptosis, indicating that miR-7 is dispensable for the maintenance of endocrine β cell mass. Furthermore, we found that miR-7a levels are decreased in obese/diabetic mouse models and human islets from obese and moderately diabetic individuals with compensated β cell function. Our results reveal an interconnecting miR-7 genomic circuit that regulates insulin granule exocytosis in pancreatic β cells and support a role for miR-7 in the adaptation of pancreatic β cell function in obesity and type 2 diabetes. PMID:24789908

  7. Somatostatin receptor expression and biological functions in endocrine pancreatic cells: review based on a doctoral thesis.

    PubMed

    Ludvigsen, Eva

    2007-01-01

    Type 1 diabetes is resulting from the selective destruction of insulin-producing betacells within the pancreatic islets. Somatostatin acts as an inhibitor of hormone secretion through specific receptors (sst1-5). All ssts were expressed in normal rat and mouse pancreatic islets, although the expression intensity and the co-expression pattern varied between ssts as well as between species. This may reflect a difference in response to somatostatin in islet cells of the two species. The Non-Obese Diabetic (NOD) mouse model is an experimental model of type 1 diabetes, with insulitis accompanied by spontaneous hyperglycaemia. Pancreatic specimens from NOD mice at different age and stage of disease were stained for ssts. The islet cells of diabetic NOD mice showed increased islet expression of sst2-5 compared to normoglycemic NOD mice. The increase in sst2-5 expression in the islets cells may suggest either a contributing factor in the process leading to diabetes, or a defense response against ongoing beta-cell destruction. Somatostatin analogues were tested on a human endocrine pancreatic tumour cell line and cultured pancreatic islets. Somatostatin analogues had an effect on cAMP accumulation, chromogranin A secretion and MAP kinase activity in the cell line. Treatment of rat pancreatic islets with somatostatin analogues with selective receptor affinity was not sufficient to induce an inhibition of insulin and glucagon secretion. However, a combination of selective analogues or non-selective analogues via costimulation of receptors can cause inhibition of hormone production. For insulin and glucagon, combinations of sst2 + sst5 and sst1 + sst2, respectively, showed a biological effect. In summary, knowledge of islet cell ssts expression and the effect of somatostatin analogues with high affinity to ssts may be valuable in the future attempts to influence beta-cell function in type 1 diabetes mellitus, since down-regulation of beta-cell function may promote survival of

  8. Pancreatitis

    MedlinePlus

    ... open. Balloon dilatation. Some endoscopes have a small balloon that the doctor uses to dilate, or stretch, a narrowed pancreatic or bile duct. A temporary stent may be placed for a few months to ...

  9. Liver Function Tests

    MedlinePlus

    ... herbal supplements you are taking. What are normal ranges for liver function tests? Normal ranges for liver function tests can vary by age, ... other factors. Laboratory test results usually provide normal ranges for each liver function test with your results. ...

  10. Activated pancreatic stellate cells can impair pancreatic islet function in mice

    PubMed Central

    Zang, Guangxiang; Sandberg, Monica; Carlsson, Per-Ola; Welsh, Nils; Jansson, Leif

    2015-01-01

    Background Pancreatic or islet fibrosis is often associated with activated pancreatic stellate cells (PSCs). PSCs are considered not only to promote fibrosis, but also to be associated with glucose intolerance in some diseases. We therefore evaluated morphological and functional relationships between islets and PSCs in the normal mouse pancreas and transplanted islets. Methods Immunohistochemistry was used to map the presence of PSCs in the normal mouse pancreas and islets implanted under the renal capsule. We isolated and cultured mouse PSCs and characterized them morphologically by immunofluorescence staining. Furthermore, we measured their cytokine production and determined their effects on insulin release from simultaneously cultured islets. Results PSCs were scattered throughout the pancreas, with occasional cells within the islets, particularly in the islet capsule. In islet transplants they were found mainly in the graft periphery. Cultured PSCs became functionally activated and produced several cytokines. Throughout the culture period they linearly increased their production of interleukin-6 and mammalian keratinocyte-derived chemokine. PSC cytokine production was not affected by acute hyperglycemia. Syngeneic islets co-cultured with PSCs for 24–48 h increased their insulin release and lowered their insulin content. However, short-term insulin release in batch-type incubations was unaffected after 48 h of co-culture. Increased islet cell caspase-3 activation and a decreased islet cell replication were consistently observed after co-culture for 2 or 7 days. Conclusion Activated PSCs may contribute to impaired islet endocrine function seen in exocrine pancreatitis and in islet fibrosis associated with some cases of type 2 diabetes. PMID:25854824

  11. Islet-1 Is Essential for Pancreatic β-Cell Function

    PubMed Central

    Ediger, Benjamin N.; Du, Aiping; Liu, Jingxuan; Hunter, Chad S.; Walp, Erik R.; Schug, Jonathan; Kaestner, Klaus H.; Stein, Roland

    2014-01-01

    Islet-1 (Isl-1) is essential for the survival and ensuing differentiation of pancreatic endocrine progenitors. Isl-1 remains expressed in all adult pancreatic endocrine lineages; however, its specific function in the postnatal pancreas is unclear. Here we determine whether Isl-1 plays a distinct role in the postnatal β-cell by performing physiological and morphometric analyses of a tamoxifen-inducible, β-cell–specific Isl-1 loss-of-function mouse: Isl-1L/L; Pdx1-CreERTm. Ablating Isl-1 in postnatal β-cells reduced glucose tolerance without significantly reducing β-cell mass or increasing β-cell apoptosis. Rather, islets from Isl-1L/L; Pdx1-CreERTm mice showed impaired insulin secretion. To identify direct targets of Isl-1, we integrated high-throughput gene expression and Isl-1 chromatin occupancy using islets from Isl-1L/L; Pdx1-CreERTm mice and βTC3 insulinoma cells, respectively. Ablating Isl-1 significantly affected the β-cell transcriptome, including known targets Insulin and MafA as well as novel targets Pdx1 and Slc2a2. Using chromatin immunoprecipitation sequencing and luciferase reporter assays, we found that Isl-1 directly occupies functional regulatory elements of Pdx1 and Slc2a2. Thus Isl-1 is essential for postnatal β-cell function, directly regulates Pdx1 and Slc2a2, and has a mature β-cell cistrome distinct from that of pancreatic endocrine progenitors. PMID:25028525

  12. Exocrine pancreatic insufficiency: accuracy and clinical value of the uniformly labelled 13C-Hiolein breath test.

    PubMed Central

    Lembcke, B; Braden, B; Caspary, W F

    1996-01-01

    BACKGROUND AND AIMS: The 13C-Hiolein breath test (98% [U-13C] labelled long chain triglyceride mixture (highly labelled triolein) was evaluated as a non-invasive, non-radioactive test for exocrine pancreatic insufficiency. Accuracy and clinical validity were examined with reference to both the secretin pancreozymin test and faecal fat analysis. METHODS: A secretin pancreozymin test and faecal fat analysis were performed in 46 patients, 30 with exocrine pancreatic insufficiency and 16 with normal pancreatic function. In all of these patients and in seven healthy volunteers (controls), a 13C-Hiolein breath test was performed using 2 mg/kg [U-13C] labelled Hiolein with a standard risk snack (1.5 g/kg; 25% fat). 13CO2/12CO2 enrichment in the exhaled breath was measured by isotope ratio mass spectrometry. RESULTS: In patients with pancreatic steatorrhoea the 13CO2 response was below the 95% confidence interval of 13CO2 exhalation in the controls. These responses were also diminished (p < 0.001) compared with patients with impaired lipase output but normal fat excretion and with disease as well as healthy controls. There was a linear correlation between stimulated lipase output and the ratio of lipase output/13CO2 response (r = 0.95). Among the 40 patients in whom direct pancreatic function testing was clinically indicated, the sensitivity of the 13C-Hiolein test for detecting steatorrhoea was 91.7%, with a specificity of 85.7%. CONCLUSIONS: In patients with pancreatic disease the 13C-Hiolein breath test reflects impaired lipase output and indicates decompensated lipolysis. The 13C-Hiolein breath test is a convenient alternative to faecal fat analysis. PMID:9026480

  13. Pancreatitis

    MedlinePlus

    ... to the abdomen. In 1 out of 4 childhood cases, a cause is never found. What are the symptoms of pancreatitis? Inflammation of the pancreas is often associated with pain in the upper abdomen and/or the back which may develop slowly, ...

  14. Microfluidic platform for assessing pancreatic islet functionality through dielectric spectroscopy

    PubMed Central

    Heileman, K.; Daoud, J.; Hasilo, C.; Gasparrini, M.; Paraskevas, S.; Tabrizian, M.

    2015-01-01

    Human pancreatic islets are seldom assessed for dynamic responses to external stimuli. Thus, the elucidation of human islet functionality would provide insights into the progression of diabetes mellitus, evaluation of preparations for clinical transplantation, as well as for the development of novel therapeutics. The objective of this study was to develop a microfluidic platform for in vitro islet culture, allowing the multi-parametric investigation of islet response to chemical and biochemical stimuli. This was accomplished through the fabrication and implementation of a microfluidic platform that allowed the perifusion of islet culture while integrating real-time monitoring using impedance spectroscopy, through microfabricated, interdigitated electrodes located along the microchamber arrays. Real-time impedance measurements provide important dielectric parameters, such as cell membrane capacitance and cytoplasmic conductivity, representing proliferation, differentiation, viability, and functionality. The perifusion of varying glucose concentrations and monitoring of the resulting impedance of pancreatic islets were performed as proof-of-concept validation of the lab-on-chip platform. This novel technique to elucidate the underlying mechanisms that dictate islet functionality is presented, providing new information regarding islet function that could improve the evaluation of islet preparations for transplantation. In addition, it will lead to a better understanding of fundamental diabetes-related islet dysfunction and the development of therapeutics through evaluation of potential drug effects. PMID:26339324

  15. Liver Function Tests

    MedlinePlus

    ... food, store energy, and remove poisons. Liver function tests are blood tests that check to see how well your liver ... hepatitis and cirrhosis. You may have liver function tests as part of a regular checkup. Or you ...

  16. Functional somatostatin receptors on a rat pancreatic acinar cell line

    SciTech Connect

    Viguerie, N.; Tahiri-Jouti, N.; Esteve, J.P.; Clerc, P.; Logsdon, C.; Svoboda, M.; Susini, C.; Vaysse, N.; Ribet, A. Mount Zion Hospital and Medical Center, San Francisco, CA Universite Libre de Bruxelles, Brussels )

    1988-07-01

    Somatostatin receptors from a rat pancreatic acinar cell line, AR4-2J, were characterized biochemically, structurally, and functionally. Binding of {sup 125}I-(Tyr{sup 11})Somatostatin to AR4-2J cells was saturable, exhibiting a single class of high-affinity binding sites with a maximal binding capacity of 258 {plus minus} 20 fmol/10{sup 6} cells. Somatostatin receptor structure was analyzed by covalently cross-linking {sup 125}I-(Tyr{sup 11})somatostatin to its plasma membrane receptors. Gel electrophoresis and autoradiography of cross-linked proteins revealed a peptide containing the somatostatin receptor. Somatostatin inhibited vasoactive intestinal peptide (VIP)-stimulated adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) formation in a dose-dependent manner. The concentration of somatostatin that caused half-maximal inhibition of cAMP formation was close to the receptor affinity for somatostatin. Pertussis toxin pretreatment of AR4-2J cells prevented somatostatin inhibition of VIP-stimulated cAMP formation as well as somatostatin binding. The authors conclude that AR4-2J cells exhibit functional somatostatin receptors that retain both specificity and affinity of the pancreatic acinar cell somatostatin receptors and act via the pertussis toxin-sensitive guanine nucleotide-binding protein N{sub i} to inhibit adenylate cyclase.

  17. DNA methylation directs functional maturation of pancreatic β cells

    PubMed Central

    Dhawan, Sangeeta; Tschen, Shuen-Ing; Zeng, Chun; Guo, Tingxia; Hebrok, Matthias; Matveyenko, Aleksey; Bhushan, Anil

    2015-01-01

    Pancreatic β cells secrete insulin in response to postprandial increases in glucose levels to prevent hyperglycemia and inhibit insulin secretion under fasting conditions to protect against hypoglycemia. β cells lack this functional capability at birth and acquire glucose-stimulated insulin secretion (GSIS) during neonatal life. Here, we have shown that during postnatal life, the de novo DNA methyltransferase DNMT3A initiates a metabolic program by repressing key genes, thereby enabling the coupling of insulin secretion to glucose levels. In a murine model, β cell–specific deletion of Dnmt3a prevented the metabolic switch, resulting in loss of GSIS. DNMT3A bound to the promoters of the genes encoding hexokinase 1 (HK1) and lactate dehydrogenase A (LDHA) — both of which regulate the metabolic switch — and knockdown of these two key DNMT3A targets restored the GSIS response in islets from animals with β cell–specific Dnmt3a deletion. Furthermore, DNA methylation–mediated repression of glucose-secretion decoupling genes to modulate GSIS was conserved in human β cells. Together, our results reveal a role for DNA methylation to direct the acquisition of pancreatic β cell function. PMID:26098213

  18. Functional annotation of rare gene aberration drivers of pancreatic cancer

    PubMed Central

    Tsang, Yiu Huen; Dogruluk, Turgut; Tedeschi, Philip M.; Wardwell-Ozgo, Joanna; Lu, Hengyu; Espitia, Maribel; Nair, Nikitha; Minelli, Rosalba; Chong, Zechen; Chen, Fengju; Chang, Qing Edward; Dennison, Jennifer B.; Dogruluk, Armel; Li, Min; Ying, Haoqiang; Bertino, Joseph R.; Gingras, Marie-Claude; Ittmann, Michael; Kerrigan, John; Chen, Ken; Creighton, Chad J.; Eterovic, Karina; Mills, Gordon B.; Scott, Kenneth L.

    2016-01-01

    As we enter the era of precision medicine, characterization of cancer genomes will directly influence therapeutic decisions in the clinic. Here we describe a platform enabling functionalization of rare gene mutations through their high-throughput construction, molecular barcoding and delivery to cancer models for in vivo tumour driver screens. We apply these technologies to identify oncogenic drivers of pancreatic ductal adenocarcinoma (PDAC). This approach reveals oncogenic activity for rare gene aberrations in genes including NAD Kinase (NADK), which regulates NADP(H) homeostasis and cellular redox state. We further validate mutant NADK, whose expression provides gain-of-function enzymatic activity leading to a reduction in cellular reactive oxygen species and tumorigenesis, and show that depletion of wild-type NADK in PDAC cell lines attenuates cancer cell growth in vitro and in vivo. These data indicate that annotating rare aberrations can reveal important cancer signalling pathways representing additional therapeutic targets. PMID:26806015

  19. Functional annotation of rare gene aberration drivers of pancreatic cancer.

    PubMed

    Tsang, Yiu Huen; Dogruluk, Turgut; Tedeschi, Philip M; Wardwell-Ozgo, Joanna; Lu, Hengyu; Espitia, Maribel; Nair, Nikitha; Minelli, Rosalba; Chong, Zechen; Chen, Fengju; Chang, Qing Edward; Dennison, Jennifer B; Dogruluk, Armel; Li, Min; Ying, Haoqiang; Bertino, Joseph R; Gingras, Marie-Claude; Ittmann, Michael; Kerrigan, John; Chen, Ken; Creighton, Chad J; Eterovic, Karina; Mills, Gordon B; Scott, Kenneth L

    2016-01-01

    As we enter the era of precision medicine, characterization of cancer genomes will directly influence therapeutic decisions in the clinic. Here we describe a platform enabling functionalization of rare gene mutations through their high-throughput construction, molecular barcoding and delivery to cancer models for in vivo tumour driver screens. We apply these technologies to identify oncogenic drivers of pancreatic ductal adenocarcinoma (PDAC). This approach reveals oncogenic activity for rare gene aberrations in genes including NAD Kinase (NADK), which regulates NADP(H) homeostasis and cellular redox state. We further validate mutant NADK, whose expression provides gain-of-function enzymatic activity leading to a reduction in cellular reactive oxygen species and tumorigenesis, and show that depletion of wild-type NADK in PDAC cell lines attenuates cancer cell growth in vitro and in vivo. These data indicate that annotating rare aberrations can reveal important cancer signalling pathways representing additional therapeutic targets. PMID:26806015

  20. Pancreatic panniculitis

    PubMed Central

    Mahawish, Karim; Iyasere, Isoken T

    2014-01-01

    We present the case of a 55-year-old Caucasian man presenting with polyarthritis, weight loss and multiple tender cutaneous nodules. Abnormal liver function tests prompted imaging of the liver which demonstrated liver metastases. Biopsy of the liver lesions confirmed the diagnosis of metastatic pancreatic neuroendocrine carcinoma. PMID:25150233

  1. Microphthalmia transcription factor regulates pancreatic β-cell function.

    PubMed

    Mazur, Magdalena A; Winkler, Marcus; Ganic, Elvira; Colberg, Jesper K; Johansson, Jenny K; Bennet, Hedvig; Fex, Malin; Nuber, Ulrike A; Artner, Isabella

    2013-08-01

    Precise regulation of β-cell function is crucial for maintaining blood glucose homeostasis. Pax6 is an essential regulator of β-cell-specific factors like insulin and Glut2. Studies in the developing eye suggest that Pax6 interacts with Mitf to regulate pigment cell differentiation. Here, we show that Mitf, like Pax6, is expressed in all pancreatic endocrine cells during mouse postnatal development and in the adult islet. A Mitf loss-of-function mutation results in improved glucose tolerance and enhanced insulin secretion but no increase in β-cell mass in adult mice. Mutant β-cells secrete more insulin in response to glucose than wild-type cells, suggesting that Mitf is involved in regulating β-cell function. In fact, the transcription of genes critical for maintaining glucose homeostasis (insulin and Glut2) and β-cell formation and function (Pax4 and Pax6) is significantly upregulated in Mitf mutant islets. The increased Pax6 expression may cause the improved β-cell function observed in Mitf mutant animals, as it activates insulin and Glut2 transcription. Chromatin immunoprecipitation analysis shows that Mitf binds to Pax4 and Pax6 regulatory regions, suggesting that Mitf represses their transcription in wild-type β-cells. We demonstrate that Mitf directly regulates Pax6 transcription and controls β-cell function. PMID:23610061

  2. Microphthalmia Transcription Factor Regulates Pancreatic β-Cell Function

    PubMed Central

    Mazur, Magdalena A.; Winkler, Marcus; Ganić, Elvira; Colberg, Jesper K.; Johansson, Jenny K.; Bennet, Hedvig; Fex, Malin; Nuber, Ulrike A.; Artner, Isabella

    2013-01-01

    Precise regulation of β-cell function is crucial for maintaining blood glucose homeostasis. Pax6 is an essential regulator of β-cell–specific factors like insulin and Glut2. Studies in the developing eye suggest that Pax6 interacts with Mitf to regulate pigment cell differentiation. Here, we show that Mitf, like Pax6, is expressed in all pancreatic endocrine cells during mouse postnatal development and in the adult islet. A Mitf loss-of-function mutation results in improved glucose tolerance and enhanced insulin secretion but no increase in β-cell mass in adult mice. Mutant β-cells secrete more insulin in response to glucose than wild-type cells, suggesting that Mitf is involved in regulating β-cell function. In fact, the transcription of genes critical for maintaining glucose homeostasis (insulin and Glut2) and β-cell formation and function (Pax4 and Pax6) is significantly upregulated in Mitf mutant islets. The increased Pax6 expression may cause the improved β-cell function observed in Mitf mutant animals, as it activates insulin and Glut2 transcription. Chromatin immunoprecipitation analysis shows that Mitf binds to Pax4 and Pax6 regulatory regions, suggesting that Mitf represses their transcription in wild-type β-cells. We demonstrate that Mitf directly regulates Pax6 transcription and controls β-cell function. PMID:23610061

  3. Extraocular muscle function testing

    MedlinePlus

    Extraocular muscle function testing examines the function of the eye muscles. A health care provider observes the movement of ... evaluate weakness or other problem in the extraocular muscles. These problems may result in double vision or ...

  4. Functional Task Test (FTT)

    NASA Technical Reports Server (NTRS)

    Bloomberg, Jacob J.; Mulavara, Ajitkumar; Peters, Brian T.; Rescheke, Millard F.; Wood, Scott; Lawrence, Emily; Koffman, Igor; Ploutz-Snyder, Lori; Spiering, Barry A.; Feeback, Daniel L.; Platts, Steven H.; Stenger, Michael B.; Lee, Stuart M.C.; Arzeno, Natalia; Feiveson, Alan H.; Ryder, Jeffrey; Garcia, Yamil; Guilliams, Mark E.

    2009-01-01

    This slide presentation reviews the Functional Task Test (FTT), an interdisciplinary testing regimen that has been developed to evaluate astronaut postflight functional performance and related physiological changes. The objectives of the project are: (1) to develop a set of functional tasks that represent critical mission tasks for the Constellation Program, (2) determine the ability to perform these tasks after space flight, (3) Identify the key physiological factors that contribute to functional decrements and (4) Use this information to develop targeted countermeasures.

  5. Pulmonary Function Tests

    PubMed Central

    Ranu, Harpreet; Wilde, Michael; Madden, Brendan

    2011-01-01

    Pulmonary function tests are valuable investigations in the management of patients with suspected or previously diagnosed respiratory disease. They aid diagnosis, help monitor response to treatment and can guide decisions regarding further treatment and intervention. The interpretation of pulmonary functions tests requires knowledge of respiratory physiology. In this review we describe investigations routinely used and discuss their clinical implications. PMID:22347750

  6. Platelet Function Tests

    MedlinePlus

    ... of the clotting process in the body ( in vivo ). A person with normal platelet function test results may still experience excessive bleeding or inappropriate clotting during and after a surgery. Most samples for platelet function testing are only stable for a very short period ...

  7. [Pancreatic Diseases].

    PubMed

    Schöfl, Rainer

    2016-06-22

    The author presents his personal choice of practical relevant papers of pancreatic diseases from 2014 to 2015. Nutritional factors and hypertriglycidemia are discussed as causes of acute pancreatitis. Tools to avoid post-ERCP(endoscopic retrograde cholangiopancreatography) pancreatitis are described and the natural course of fluid collections and pseudocysts is demonstrated. The value of secretin-MRCP(magnetic resonance cholangiopancreatography) for diagnosis of chronic pancreatitis is illustrated. Data help to choose the minimally effective prednisolone dose in autoimmune pancreatitis. The increased prevalence of fractures in patients with chronic pancreatitis highlights the necessity of screening for bone density loss. The association of vitamin D intake with pancreatic cancer is described. The probability of cancer in IPNM is shown and innovative surgical concepts to reduce the loss of pancreatic function are presented. Finally neoadjuvant concepts for the treatment of pancreatic cancer are highlighted. PMID:27329710

  8. Sperm function test

    PubMed Central

    Talwar, Pankaj; Hayatnagarkar, Suryakant

    2015-01-01

    With absolute normal semen analysis parameters it may not be necessary to shift to specialized tests early but in cases with borderline parameters or with history of fertilization failure in past it becomes necessary to do a battery of tests to evaluate different parameters of spermatozoa. Various sperm function tests are proposed and endorsed by different researchers in addition to the routine evaluation of fertility. These tests detect function of a certain part of spermatozoon and give insight on the events in fertilization of the oocyte. The sperms need to get nutrition from the seminal plasma in the form of fructose and citrate (this can be assessed by fructose qualitative and quantitative estimation, citrate estimation). They should be protected from the bad effects of pus cells and reactive oxygen species (ROS) (leukocyte detection test, ROS estimation). Their number should be in sufficient in terms of (count), structure normal to be able to fertilize eggs (semen morphology). Sperms should have intact and functioning membrane to survive harsh environment of vagina and uterine fluids (vitality and hypo-osmotic swelling test), should have good mitochondrial function to be able to provide energy (mitochondrial activity index test). They should also have satisfactory acrosome function to be able to burrow a hole in zona pellucida (acrosome intactness test, zona penetration test). Finally, they should have properly packed DNA in the nucleus to be able to transfer the male genes (nuclear chromatic decondensation test) to the oocyte during fertilization. PMID:26157295

  9. Sperm function test.

    PubMed

    Talwar, Pankaj; Hayatnagarkar, Suryakant

    2015-01-01

    With absolute normal semen analysis parameters it may not be necessary to shift to specialized tests early but in cases with borderline parameters or with history of fertilization failure in past it becomes necessary to do a battery of tests to evaluate different parameters of spermatozoa. Various sperm function tests are proposed and endorsed by different researchers in addition to the routine evaluation of fertility. These tests detect function of a certain part of spermatozoon and give insight on the events in fertilization of the oocyte. The sperms need to get nutrition from the seminal plasma in the form of fructose and citrate (this can be assessed by fructose qualitative and quantitative estimation, citrate estimation). They should be protected from the bad effects of pus cells and reactive oxygen species (ROS) (leukocyte detection test, ROS estimation). Their number should be in sufficient in terms of (count), structure normal to be able to fertilize eggs (semen morphology). Sperms should have intact and functioning membrane to survive harsh environment of vagina and uterine fluids (vitality and hypo-osmotic swelling test), should have good mitochondrial function to be able to provide energy (mitochondrial activity index test). They should also have satisfactory acrosome function to be able to burrow a hole in zona pellucida (acrosome intactness test, zona penetration test). Finally, they should have properly packed DNA in the nucleus to be able to transfer the male genes (nuclear chromatic decondensation test) to the oocyte during fertilization. PMID:26157295

  10. Comparison of the sensitivity of different diagnostic tests for pancreatitis in cats.

    PubMed

    Gerhardt, A; Steiner, J M; Williams, D A; Kramer, S; Fuchs, C; Janthur, M; Hewicker-Trautwein, M; Nolte, I

    2001-01-01

    The objective of this study was to compare the sensitivity of different diagnostic tests for pancreatitis in cats. Twenty-one cats with confirmed pancreatitis were evaluated at the Small Animal Clinic of the School of Veterinary Medicine in Hannover, Germany, between September 1997 and January 1999. Clinical signs of affected cats were nonspecific, with 95% of the cats showing anorexia and 86% lethargy. Also, hematologic and biochemical abnormalities of affected cats were nonspecific. Serum feline trypsin-like immunoreactivity (fTLI) in these 21 cats with pancreatitis was 127.5 +/- 109.5 microg/L (mean +/- SD; range, 24-500 microg/L). Fourteen of the 21 cats with pancreatitis had complicating conditions. Their serum fTLI was 153.9 +/- 124.3 microg/L (mean +/- SD; range, 29 500 microg/L). In this study, abdominal ultrasound showed a sensitivity for pancreatitis of 24%, and abdominal computed tomography had a sensitivity of 20%. Serum fTLI had a sensitivity between 86% when a cut-off value of 49 microg/L was used (upper limit of the control range) and 33% when a cut-off value of 100 microg/L was used. We conclude that in this group of cats with pancreatitis, measurement of serum fTLI was the most sensitive diagnostic test of those evaluated. Abdominal ultrasound, however, may be a valuable diagnostic tool in some cats with pancreatitis. PMID:11467589

  11. LKB1 Regulates Pancreatic β Cell Size, Polarity, and Function

    PubMed Central

    Granot, Zvi; Swisa, Avital; Magenheim, Judith; Stolovich-Rain, Miri; Fujimoto, Wakako; Manduchi, Elisabetta; Miki, Takashi; Lennerz, Jochen K.; Stoeckert, Christian J.; Meyuhas, Oded; Seino, Susumu; Permutt, M. Alan; Piwnica-Worms, Helen; Bardeesy, Nabeel; Dor, Yuval

    2009-01-01

    Summary Pancreatic β cells, organized in the islets of Langerhans, sense glucose and secrete appropriate amounts of insulin. We have studied the roles of LKB1, a conserved kinase implicated in the control of cell polarity and energy metabolism, in adult β cells. LKB1-deficient β cells show a dramatic increase in insulin secretion in vivo. Histologically, LKB1-deficient β cells have striking alterations in the localization of the nucleus and cilia relative to blood vessels, suggesting a shift from hepatocyte-like to columnar polarity. Additionally, LKB1 deficiency causes a 65% increase in β cell volume. We show that distinct targets of LKB1 mediate these effects. LKB1 controls β cell size, but not polarity, via the mTOR pathway. Conversely, the precise position of the β cell nucleus, but not cell size, is controlled by the LKB1 target Par1b. Insulin secretion and content are restricted by LKB1, at least in part, via AMPK. These results expose a molecular mechanism, orchestrated by LKB1, for the coordinated maintenance of β cell size, form, and function. PMID:19808022

  12. Pancreatic beta cell function in the fetal pig and sow.

    PubMed

    Fowden, A L; Comline, R S; Silver, M

    1982-04-01

    Insulin secretion was investigated in acutely anaesthetized and chronically catheterized sows and their fetuses during late gestation. In the conscious animals, the mean fetal concentration of plasma insulin was 8.4 +/- 1.5 microunits/ml which was significantly less than the corresponding maternal value of 33.9 +/- 6.5 microunits/ml (n = 12, P less than 0.01). The plasma concentrations of insulin and glucose in the new-born piglets from these litters were not significantly different from the values observed in utero. The plasma concentration of insulin in the anaesthetized fetuses was significantly less than that in the chronically catheterized piglets over the same range of glucose levels. In the chronically catheterized animals, both fetal and maternal levels of insulin rose with increasing concentrations of plasma glucose while under acute conditions there was no correlation between the endogenous concentrations of insulin and glucose in either the fetuses or their mothers. Infusion of exogenous glucose (0.5 g as a 50% solution in 0.9% NaCl) stimulated the release of insulin in all the chronically catheterized fetuses studied but rarely increased the concentration of insulin in the anaesthetized fetusus. The present findings show that anaesthesia and surgery depress pancreatic beta cell function in the pig, particularly in the fetus. PMID:7043523

  13. GEMMs as preclinical models for testing pancreatic cancer therapies.

    PubMed

    Gopinathan, Aarthi; Morton, Jennifer P; Jodrell, Duncan I; Sansom, Owen J

    2015-10-01

    Pancreatic ductal adenocarcinoma is the most common form of pancreatic tumour, with a very limited survival rate and currently no available disease-modifying treatments. Despite recent advances in the production of genetically engineered mouse models (GEMMs), the development of new therapies for pancreatic cancer is still hampered by a lack of reliable and predictive preclinical animal models for this disease. Preclinical models are vitally important for assessing therapies in the first stages of the drug development pipeline, prior to their transition to the clinical arena. GEMMs carry mutations in genes that are associated with specific human diseases and they can thus accurately mimic the genetic, phenotypic and physiological aspects of human pathologies. Here, we discuss different GEMMs of human pancreatic cancer, with a focus on the Lox-Stop-Lox (LSL)-Kras(G12D); LSL-Trp53(R172H); Pdx1-cre (KPC) model, one of the most widely used preclinical models for this disease. We describe its application in preclinical research, highlighting its advantages and disadvantages, its potential for predicting clinical outcomes in humans and the factors that can affect such outcomes, and, finally, future developments that could advance the discovery of new therapies for pancreatic cancer. PMID:26438692

  14. GEMMs as preclinical models for testing pancreatic cancer therapies

    PubMed Central

    Gopinathan, Aarthi; Morton, Jennifer P.; Jodrell, Duncan I.; Sansom, Owen J.

    2015-01-01

    ABSTRACT Pancreatic ductal adenocarcinoma is the most common form of pancreatic tumour, with a very limited survival rate and currently no available disease-modifying treatments. Despite recent advances in the production of genetically engineered mouse models (GEMMs), the development of new therapies for pancreatic cancer is still hampered by a lack of reliable and predictive preclinical animal models for this disease. Preclinical models are vitally important for assessing therapies in the first stages of the drug development pipeline, prior to their transition to the clinical arena. GEMMs carry mutations in genes that are associated with specific human diseases and they can thus accurately mimic the genetic, phenotypic and physiological aspects of human pathologies. Here, we discuss different GEMMs of human pancreatic cancer, with a focus on the Lox-Stop-Lox (LSL)-KrasG12D; LSL-Trp53R172H; Pdx1-cre (KPC) model, one of the most widely used preclinical models for this disease. We describe its application in preclinical research, highlighting its advantages and disadvantages, its potential for predicting clinical outcomes in humans and the factors that can affect such outcomes, and, finally, future developments that could advance the discovery of new therapies for pancreatic cancer. PMID:26438692

  15. Pancreatic Tuberculosis or Autoimmune Pancreatitis

    PubMed Central

    Saif, Muhammad Wasif

    2014-01-01

    Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis. PMID:24839445

  16. Relationships between leucine and the pancreatic exocrine function for improving starch digestibility in ruminants.

    PubMed

    Liu, K; Liu, Y; Liu, S M; Xu, M; Yu, Z P; Wang, X; Cao, Y C; Yao, J H

    2015-04-01

    Four Holstein heifers (215 ± 7 kg; means ± SD), fitted with one pancreatic pouch, duodenal re-entrant cannulas, and duodenal infusion catheters, were used in this experiment. In phase 1, the 24-h profile of pancreatic fluid was determined. Pancreatic fluid flow peaked 1h after feeding, but peaks of similar magnitude also occurred before the morning feed, necessitating 24-h collection of pancreatic fluid to estimate daily excretion. In phase 2, the effects of duodenal infusions of 0, 10, 20, or 30 g of leucine on pancreatic fluid flow were determined in a 4 × 4 Latin square design. The leucine was infused for 12h in 2,500 mL of the infusate, and samples of pancreatic fluid and jugular blood were collected in 1-h intervals from the beginning of the infusion for 36 h. The results showed that the secretion rate of pancreatic fluid (mL/h) was significantly higher in 10-g leucine group than the other groups (mL/h). Protein concentration (mg/mL) in pancreatic fluid was elevated proportional to the amount of leucine infused. Leucine infusions increased both the concentration (U/mL) and secretion rate (U/h) of α-amylase. Infusion of 10 g of leucine also increased the secretion rates (U/h) of trypsin, chymotrypsin, and lipase, but did not change their concentrations. No significant effects of leucine infusions on plasma glucose and insulin concentrations were found. The results indicate that leucine could act as a nutrient signal to stimulate α-amylase production and pancreatic exocrine function in dairy heifers. PMID:25648818

  17. Functional implications of long non-coding RNAs in the pancreatic islets of Langerhans

    PubMed Central

    Esguerra, Jonathan L. S.; Eliasson, Lena

    2014-01-01

    Type-2 diabetes (T2D) is a complex disease characterized by insulin resistance in target tissues and impaired insulin release from pancreatic beta cells. As central tissue of glucose homeostasis, the pancreatic islet continues to be an important focus of research to understand the pathophysiology of the disease. The increased access to human pancreatic islets has resulted in improved knowledge of islet function, and together with advances in RNA sequencing and related technologies, revealed the transcriptional and epigenetic landscape of human islet cells. The discovery of thousands of long non-coding RNA (lncRNA) transcripts highly enriched in the pancreatic islet and/or specifically expressed in the beta-cells, points to yet another layer of gene regulation of many hitherto unknown mechanistic principles governing islet cell functions. Here we review fundamental islet physiology and propose functional implications of the lncRNAs in islet development and endocrine cell functions. We also take into account important differences between rodent and human islets in terms of morphology and function, and suggest how species-specific lncRNAs may partly influence gene regulation to define the unique phenotypic identity of an organism and the functions of its constituent cells. The implication of primate-specific lncRNAs will be far-reaching in all aspects of diabetes research, but most importantly in the identification and development of novel targets to improve pancreatic islet cell functions as a therapeutic approach to treat T2D. PMID:25071836

  18. Pancreatic exocrine insufficiency after pancreatic surgery.

    PubMed

    Goess, Ruediger; Ceyhan, Güralp O; Friess, Helmut

    2016-06-01

    Pancreatic exocrine insufficiency is an often-underestimated complication following pancreatic surgery. After recent advances in managing acute postoperative complications the focus of current research is now shifting onto the long-term complications following pancreatectomy. Weight loss and steatorrhea as typical symptoms have high influence on the quality of life in the postoperative period. Malnutrition-related symptoms occur late and are often misinterpreted. Enzyme replacement therapy is more or less the only possible treatment option, even though not many controlled trials have been performed in this field. In this review we summarized the pathophysiology, diagnosis, risk factors and treatment options of exocrine insufficiency and focus mainly on patients with pancreaticoduodenectomy (classical Whipple), pylorus-preserving pancreaticoduodenectomy (ppWhipple) or distal pancreatectomy. Incidence of pancreatic exocrine insufficiency after surgery depends mainly on the initial diagnosis, the preoperative exocrine function and is associated with the extent of parenchyma resection. Diagnosing exocrine failure after surgery can be difficult and specific function tests are commonly not routinely performed. Starting and monitoring of enzyme replacement treatment is more based on clinical symptoms, than on objective markers. To improve the performance status of postsurgical patients it is important to consider pancreatic exocrine function as one aspect of quality of life. Further clinical trials should be initiated to gain more specific knowledge about the influence of the different pancreatic resections on pancreatic exocrine function to initialize proper treatment even before major clinical symptoms occur. PMID:27058237

  19. Loss of cftr function leads to pancreatic destruction in larval zebrafish

    PubMed Central

    Navis, Adam; Bagnat, Michel

    2016-01-01

    The development and function of many internal organs requires precisely regulated fluid secretion. A key regulator of vertebrate fluid secretion is an anion channel, the cystic fibrosis transmembrane conductance regulator (CFTR). Loss of CFTR function leads to defects in fluid transport and cystic fibrosis (CF), a complex disease characterized by a loss of fluid secretion and mucus buildup in many organs including the lungs, liver, and pancreas. Several animal models including mouse, ferret and pig have been generated to investigate the pathophysiology of CF. However, these models have limited accessibility to early processes in the development of CF and are not amenable for forward genetic or chemical screens. Here, we show that Cftr is expressed and localized to the apical membrane of the zebrafish pancreatic duct and that loss of cftr function leads to destruction of the exocrine pancreas and a cystic fibrosis phenotype that mirrors human disease. Our analyses reveal that the cftr mutant pancreas initially develops normally, then rapidly loses pancreatic tissue during larval life, reflecting pancreatic disease in CF. Altogether, we demonstrate that the cftr mutant zebrafish is a powerful new model for pancreatitis and pancreatic destruction in CF. This accessible model will allow more detailed investigation into the mechanisms that drive CF of the pancreas and facilitate development of new therapies to treat the disease. PMID:25592226

  20. IL17 Functions through the Novel REG3β-JAK2-STAT3 Inflammatory Pathway to Promote the Transition from Chronic Pancreatitis to Pancreatic Cancer.

    PubMed

    Loncle, Celine; Bonjoch, Laia; Folch-Puy, Emma; Lopez-Millan, Maria Belen; Lac, Sophie; Molejon, Maria Inés; Chuluyan, Eduardo; Cordelier, Pierre; Dubus, Pierre; Lomberk, Gwen; Urrutia, Raul; Closa, Daniel; Iovanna, Juan L

    2015-11-15

    Pancreatic ductal adenocarcinoma (PDAC) offers an optimal model for discovering "druggable" molecular pathways that participate in inflammation-associated cancer development. Chronic pancreatitis, a common prolonged inflammatory disease, behaves as a well-known premalignant condition that contributes to PDAC development. Although the mechanisms underlying the pancreatitis-to-cancer transition remain to be fully elucidated, emerging evidence supports the hypothesis that the actions of proinflammatory mediators on cells harboring Kras mutations promote neoplastic transformation. Recent elegant studies demonstrated that the IL17 pathway mediates this phenomenon and can be targeted with antibodies, but the downstream mechanisms by which IL17 functions during this transition are currently unclear. In this study, we demonstrate that IL17 induces the expression of REG3β, a well-known mediator of pancreatitis, during acinar-to-ductal metaplasia and in early pancreatic intraepithelial neoplasia (PanIN) lesions. Furthermore, we found that REG3β promotes cell growth and decreases sensitivity to cell death through activation of the gp130-JAK2-STAT3-dependent pathway. Genetic inactivation of REG3β in the context of oncogenic Kras-driven PDAC resulted in reduced PanIN formation, an effect that could be rescued by administration of exogenous REG3β. Taken together, our findings provide mechanistic insight into the pathways underlying inflammation-associated pancreatic cancer, revealing a dual and contextual pathophysiologic role for REG3β during pancreatitis and PDAC initiation. PMID:26404002

  1. Glucocorticoid overexposure in neonatal life alters pancreatic beta-cell function in newborn foals.

    PubMed

    Jellyman, J K; Allen, V L; Holdstock, N B; Fowden, A L

    2013-01-01

    Studies in humans and animals have linked abnormal programming of adult tissue function to excess glucocorticoids during perinatal development. The current study investigated the hypothesis that physiological variations in glucocorticoid concentrations during early neonatal life of the foal alter the secretory responses of the pancreatic β cells 2 and 12 wk after treatment. Spontaneously delivered foals received either saline or long-acting ACTH for 5 d from 1 d after birth to maintain an endogenous rise in cortisol concentrations. Starting at d 10, pancreatic β cell function was studied using an intravenous (i.v.) glucose tolerance test, an i.v. arginine challenge, and an i.v. tolbutamide challenge. The maximum increment in plasma insulin achieved in response to exogenous glucose was less in ACTH-treated foals at both 2 and 12 wk of age (P<0.05). By 12 wk of age, developmental changes also occurred in the magnitude and biphasic pattern of glucose-stimulated insulin release. The area under the insulin curve during the early phase of insulin secretion (0 to 30 min) was not different between the 2- and 12-wk-old animals but was significantly greater during the later phase (30 to 120 min) at 12 wk than at 2 wk (P<0.05). Arginine infusion induced a brief 5 to 15 min increase in plasma concentrations of insulin that was not different in saline- and ACTH-treated foals. The β-cell response to tolbutamide infusion was rapid and monophasic, and there was no difference (P>0.05) in the area under the insulin curve with treatment at 2 or at 12 wk. However, after tolbutamide, plasma insulin concentrations remained increased for a longer period in the ACTH-treated than in the saline-treated foals at 12 wk of age (P<0.05). Hence, this is the first study to show altered pancreatic β-cell function after ACTH-induced glucocorticoid overexposure during early postnatal life in foals. PMID:23100584

  2. Adrenal function testing.

    PubMed

    Dluhy, R G

    1978-12-01

    Glucocorticoid stimulation and suppression tests are essential to the definitive diagnosis of diseases of the hypothalamic-pituitary-adrenal axis, because they document abnormal physiologic control of hormonal secretion. Similarly, diseases of the renin-angiotensin-aldosterone axis are diagnosed by mineralocorticoid stimulation and suppression testing. [Ed. Note: See Moore TJ, Williams GH: Adrenal causes of hypertension, in this issue.] Unlike tests of glucocorticoid function, testing of the renin-angiotension-aldosterone system is more complicated, because knowledge of posture and dietary sodium are necessary to interpret the results. However, measurement of the tropic hormone renin and plasma levels of aldosterone can be accurately made, allowing precise definition of this system. Errors are most commonly encountered when dynamic tests of cortisol output are performed in patients taking medications that may interfere with the assays or with the metabolism of the administered compounds, such as dexamethasone or metyrapone. Abnormal, spurious values may also be obtained in some individuals who do not have adrenocortical hyperfunction if they are very obese or if testing is performed in a setting of clinical stress. Careful attention to these pitfalls will avoid errors and allow the clinician to arrive at the correct diagnosis. PMID:216524

  3. Distribution of pancreatic B cell imaging agent 99mTc-DTPA-NGN2 in the body and animal experimental research on pancreatic B cell functional imaging

    PubMed Central

    Liu, Zhi-Hua; Xie, Ying; Tang, Jun; Liu, Chun-Feng

    2016-01-01

    Purpose: To explore the feasibility of the application of 99mTc-DTPA-Nateglinide as a nuclear medicine imaging agent for evaluating pancreatic B cell function. Methods: (1) Distribution of the experiment: Forty-two mice were selected and divided into seven groups. Each mice was injected with 3.7 MBq (100 μCi) of 99mTc-DTPA-NGN2 from the vena caudalis and was sacrificed by bloodletting at five minutes, 15 minutes, 30 minutes, one hour, two hours, four hours and six hours, respectively. Then, their tissues and organs such as the heart, liver, spleen, brain, kidneys, bones, small bowels, stomach and pancreas,and blood were collected, weighted, and their radioactivity was tested. Subsequently, the percentage injection dose rate (%ID/g) per gram of tissue was calculated. (2) Imaging experiment: Thirty-five mice were selected and divided into seven groups. Each was injected with 18.5 MBq (100 μCi) of 99mTc-DTPA-NGN2 from the vena caudalis and imaging were conducted at the same time as above. (3) Forty-eight Wistar rats were attained and randomly divided into four groups. The first group served as the healthy control group, while the second, third and fourth groups were diabetic model groups induced by intraperitoneally injecting STZ at different doses. Each group was injected with 99mTc-DTPA-Nateglinide from the vena caudalis, and radiological evaluations were conducted at 30 minutes, one hour, 1.5 hours and two hours, respectively. The data obtained were estimated using a correlation comparison with the levels of insulin and immunohistochemical count of beta cells. Results: The 99mTc-DTPA-Nateglinide demonstrated good imaging in the pancreases of mice and rats, and was positively correlated to the level of insulin and the number of pancreatic beta cells. Conclusion: Pancreatic beta cell imaging using 99mTc-DTPA-Nateglinide may be a method to evaluate pancreatic beta cell function. PMID:27186309

  4. Pediatric Arm Function Test

    PubMed Central

    Uswatte, Gitendra; Taub, Edward; Griffin, Angi; Rowe, Jan; Vogtle, Laura; Barman, Joydip

    2012-01-01

    Objective Although there are several validated upper-extremity measures in young children with cerebral palsy (CP), none primarily assess capacity to carry out actions and tasks with the more-affected arm. To address this need, we developed the Pediatric Arm Function Test (PAFT), which involves behavioral observation of how children use their more-affected arm during structured play in the laboratory or clinic. This paper evaluates the reliability and validity of the PAFT Functional Ability scale. Design In Study 1, 20 children between 2–8 years with a wide range of upper-extremity hemiparesis due to CP completed the PAFT on two occasions separated by three weeks. In Study 2, 41 children between 2–6 years with similar characteristics completed the PAFT and received a grade reflecting severity of more-affected arm motor impairment. Results In Study 1, the PAFT test-retest reliability correlation coefficient was 0.74. In Study 2, convergent validity was supported by a strong, inverse correlation (r = −0.6, p < .001) between PAFT scores and grade of impairment. Conclusions The PAFT Functional Ability scale is a reliable and valid measure of more-affected arm motor capacity in children with CP between 2–6 years. It can be employed to measure upper-extremity neurorehabilitation outcome. PMID:23103486

  5. The effect of exocrine pancreatic function on chloramphenicol pharmacokinetics in patients with cystic fibrosis.

    PubMed

    Dickinson, C J; Reed, M D; Stern, R C; Aronoff, S C; Yamashita, T S; Blumer, J L

    1988-04-01

    The effect of exocrine pancreatic function on the pharmacokinetics of the choramphenicol oral capsule (CAP-base), chloramphenicol palmitate oral liquid (CAP-P), and chloramphenicol succinate intravenous (CAP-S) formulations was evaluated in 10 patients, aged 16-30 yr, with cystic fibrosis. Pancreatic insufficiency was assessed in each patient by measuring the absorption of p-amino-benzoic acid after oral administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid which requires chymotrypsin to cleave p-aminobenzoic from the parent molecule. In a controlled cross-over design, the overall biodisposition of each formulation was assessed in each patient with or without concurrent administration of oral pancreatic enzymes. The relative amounts of active chloramphenicol available in systemic circulation was CAP-base greater than CAP-S greater than CAP-P. Pancreatic enzyme replacement had little effect on the biodisposition parameters for the CAP-base and CAP-S formulation, but significantly increased the peak concentration and bioavailability of the CAP-P formulation. Although pancreatic enzyme replacement improved the absorption characteristics of the CAP-P formulation, absorption remained prolonged and unreliable. Serum concentration-time profiles for either CAP-base or CAP-S consistently exceeded the MIC of important nonpseudomonal pathogens. This finding was not observed after CAP-P administration independent of pancreatic enzyme replacement. The results of this study support the continued clinical use of either CAP-base or CAP-S, but the cautious use of CAP-P formulations in CF patients with concurrent pancreatic insufficiency. PMID:3374992

  6. [Are urgent imaging tests indicated in the management of acute pancreatitis?].

    PubMed

    Fornell Pérez, R; Lozano Rodríguez, A

    2016-01-01

    Acute pancreatitis is a common emergency within abdominal disease. It is accepted that two of three conditions must be fulfilled for its diagnosis: characteristic clinical presentation, characteristic laboratory findings, and/or characteristic diagnostic imaging findings. The first two conditions are the most often used, probably for reasons of efficiency and frequency. Nevertheless, the need for imaging studies is sometimes a source of conflict. For this reason, we decided to review the current evidence regarding the indication of urgent imaging tests in the management of acute pancreatitis. PMID:26655802

  7. The effect of smoking cessation pharmacotherapies on pancreatic beta cell function

    SciTech Connect

    Woynillowicz, Amanda K.; Raha, Sandeep; Nicholson, Catherine J.; Holloway, Alison C.

    2012-11-15

    The goal of our study was to evaluate whether drugs currently used for smoking cessation (i.e., nicotine replacement therapy, varenicline [a partial agonist at nicotinic acetylcholine receptors (nAChR)] and bupropion [which acts in part as a nAChR antagonist]) can affect beta cell function and determine the mechanism(s) of this effect. INS-1E cells, a rat beta cell line, were treated with nicotine, varenicline and bupropion to determine their effects on beta cell function, mitochondrial electron transport chain enzyme activity and cellular/oxidative stress. Treatment of INS-1E cells with equimolar concentrations (1 μM) of three test compounds resulted in an ablation of normal glucose-stimulated insulin secretion by the cells. This disruption of normal beta cell function was associated with mitochondrial dysfunction since all three compounds tested significantly decreased the activity of mitochondrial electron transport chain enzyme activity. These results raise the possibility that the currently available smoking cessation pharmacotherapies may also have adverse effects on beta cell function and thus glycemic control in vivo. Therefore whether or not the use of nicotine replacement therapy, varenicline and bupropion can cause endocrine changes which are consistent with impaired pancreatic function warrants further investigation. -- Highlights: ► Smoking cessation drugs have the potential to disrupt beta cell function in vitro. ► The effects of nicotine, varenicline and bupropion are similar. ► The impaired beta cell function is mediated by mitochondrial dysfunction. ► If similar effects are seen in vivo, these drugs may increase the risk of diabetes.

  8. Functional annotation of rare gene aberration drivers of pancreatic cancer | Office of Cancer Genomics

    Cancer.gov

    As we enter the era of precision medicine, characterization of cancer genomes will directly influence therapeutic decisions in the clinic. Here we describe a platform enabling functionalization of rare gene mutations through their high-throughput construction, molecular barcoding and delivery to cancer models for in vivo tumour driver screens. We apply these technologies to identify oncogenic drivers of pancreatic ductal adenocarcinoma (PDAC).

  9. Computed Tomography of Pancreatitis and Pancreatic Cancer.

    PubMed

    Furlow, Bryant

    2015-01-01

    Pancreatic disease often is asymptomatic until tissue damage and complications occur or until malignancies have reached advanced stages and have metastasized. Contrast-enhanced multidetector computed tomography plays a central role in diagnosing, staging, and treatment planning for pancreatitis and pancreatic cancer. This article introduces the functional anatomy of the pancreas and common bile duct and the epidemiology, pathobiology, and computed tomography imaging of pancreatitis, calculi, and pancreatic cancer. PMID:26199449

  10. Can Pancreatic Cancer Be Found Early?

    MedlinePlus

    ... Topic Signs and symptoms of pancreatic cancer Can pancreatic cancer be found early? Pancreatic cancer is hard to ... Testing: What You Need to Know . Testing for pancreatic cancer in people at high risk For people in ...

  11. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez-Muñoz, J Enrique

    2014-09-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the prediction of the fibrosis degree of the gland, the evaluation of patients with asymptomatic hyperenzimemia, the medical and surgical treatment of abdominal pain and the knowledge of the natural history of the autoimmune pancreatitis. In patients with indetermined EUS findings of chronic pancreatitis, a new endoscopic ultrasound examination in the follow-up is of help to confirm or to exclude the disease. Smoking, number of relapses, results of pancreatic function tests and EUS findings allow predicting the degree of pancreatic fibrosis in patients with chronic pancreatitis. Antioxidant therapy has shown to be effective in reducing pain secondary to chronic pancreatitis, although the type and optimal dose of antioxidants remains to be elucidated. Development of intestinal bacterial overgrowth is frequent in patients with chronic pancreatitis, but its impact on symptoms is unknown and deserves further investigations. Finally, autoimmune pancreatitis relapses in about half of the patients with either type 1 or type 2 disease; relapses frequently occur within the first two years of follow-up. PMID:25294271

  12. Minireview: Thioredoxin-Interacting Protein: Regulation and Function in the Pancreatic β-Cell

    PubMed Central

    2014-01-01

    Pancreatic β-cells are responsible for insulin production, and loss of functional β-cell mass is now recognized as a critical step in the pathogenesis of both type 1 and type 2 diabetes. However, the factors controlling the life and death of the pancreatic β-cell have only started to be elucidated. Discovered as the top glucose-induced gene in a human islet microarray study 12 years ago, thioredoxin-interacting protein (TXNIP) has now emerged as such a key player in pancreatic β-cell biology. Since then, β-cell expression of TXNIP has been found to be tightly regulated by multiple factors and to be dramatically increased in diabetic islets. Elevated TXNIP levels induce β-cell apoptosis, whereas TXNIP deficiency protects against type 1 and type 2 diabetes by promoting β-cell survival. TXNIP interacts with and inhibits thioredoxin and thereby controls the cellular redox state, but it also belongs to the α-arrestin family of proteins and regulates a variety of metabolic processes. Most recently, TXNIP has been discovered to control β-cell microRNA expression, β-cell function, and insulin production. In this review, the current state of knowledge regarding regulation and function of TXNIP in the pancreatic β-cell and the implications for drug development are discussed. PMID:24911120

  13. SU-E-J-07: A Functional MR Protocol for the Pancreatic Tumor Delineation

    SciTech Connect

    Andreychenko, A; Heerkens, H; Meijer, G; Vulpen, M van; Lagendijk, J; Berg, C van den

    2014-06-01

    Purpose: Pancreatic cancer is one of the cancers with the poorest survival prognosis. At the time of diagnosis most of pancreatic cancers are unresectable and those patients can be treated by radiotherapy. Radiotherapy for pancreatic cancer is limited due to uncertainties in CT-based delineations. MRI provides an excellent soft tissue contrast. Here, an MR protocol is developed to improve delineations for radiotherapy treatment of pancreatic cancer. In a later stage this protocol can also be used for on-line visualization of the pancreas during MRI guided treatments. Methods: Nine pancreatic cancer patients were included. The MR protocol included T2 weighted(T2w), T1 weighted(T1w), diffusion weighted(DWI) and dynamic contrast enhanced(DCE) techniques. The tumor was delineated on T2w and T1w MRI by an experienced radiation oncologist. Healthy pancreas or pancreatitis (assigned by the oncologist based on T2w) areas were also delineated. Apparent diffusion coefficient(ADC), and area under the curve(AUC)/time to peak(TTP) maps were obtained from DWI and DCE scans, respectively. Results: A clear demarcation of tumor area was visible on b800 DWI images in 5 patients. ADC maps of those patients characterized tumor as an area with restricted water diffusion. Tumor delineations based on solely DCE were possible in 7 patients. In 6 of those patients AUC maps demonstrated tumor heterogeneity: a hypointense area with a hyperintense ring. TTP values clearly discriminated the tumor and the healthy pancreas but could not distinguish tumor and the pancreatitis accurately. Conclusion: MR imaging results in a more pronounced tumor contrast than contrast enhanced CT. The addition of quantitative, functional MRI provides valuable, additional information to the radiation oncologist on the spatial tumor extent by discriminating tumor from the healthy pancreas(TTP, DWI) and characterizing the tumor(ADC). Our findings indicate that tumor delineation in pancreatic cancer can greatly

  14. Alcohol Disrupts Levels and Function of the Cystic Fibrosis Transmembrane Conductance Regulator to Promote Development of Pancreatitis

    PubMed Central

    Maléth, József; Balázs, Anita; Pallagi, Petra; Balla, Zsolt; Kui, Balázs; Katona, Máté; Judák, Linda; Németh, István; Kemény, Lajos V.; Rakonczay, Zoltán; Venglovecz, Viktória; Földesi, Imre; Pető, Zoltán; Somorácz, Áron; Borka, Katalin; Perdomo, Doranda; Lukacs, Gergely L.; Gray, Mike A.; Monterisi, Stefania; Zaccolo, Manuela; Sendler, Matthias; Mayerle, Julia; Kühn, Jens-Peter; Lerch, Markus M.; Sahin-Tóth, Miklós; Hegyi, Péter

    2015-01-01

    BACKGROUND & AIMS Excessive consumption of ethanol is one of the most common causes of acute and chronic pancreatitis. Alterations to the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) also cause pancreatitis. However, little is known about the role of CFTR in the pathogenesis of alcohol-induced pancreatitis. METHODS We measured CFTR activity based on chloride concentrations in sweat from patients with cystic fibrosis, patients admitted to the emergency department because of excessive alcohol consumption, and healthy volunteers. We measured CFTR levels and localization in pancreatic tissues and in patients with acute or chronic pancreatitis induced by alcohol. We studied the effects of ethanol, fatty acids, and fatty acid ethyl esters on secretion of pancreatic fluid and HCO3− , levels and function of CFTR, and exchange of Cl− for HCO3− in pancreatic cell lines as well as in tissues from guinea pigs and CFTR knockout mice after administration of alcohol. RESULTS Chloride concentrations increased in sweat samples from patients who acutely abused alcohol but not in samples from healthy volunteers, indicating that alcohol affects CFTR function. Pancreatic tissues from patients with acute or chronic pancreatitis had lower levels of CFTR than tissues from healthy volunteers. Alcohol and fatty acids inhibited secretion of fluid and HCO3− , as well as CFTR activity, in pancreatic ductal epithelial cells. These effects were mediated by sustained increases in concentrations of intracellular calcium and adenosine 3’,5’-cyclic monophosphate, depletion of adenosine triphosphate, and depolarization of mitochondrial membranes. In pancreatic cell lines and pancreatic tissues of mice and guinea pigs, administration of ethanol reduced expression of CFTR messenger RNA, reduced the stability of CFTR at the cell surface, and disrupted folding of CFTR at the endoplasmic reticulum. CFTR knockout mice given ethanol or fatty acids developed more

  15. mTOR plays critical roles in pancreatic cancer stem cells through specific and stemness-related functions

    NASA Astrophysics Data System (ADS)

    Matsubara, Shyuichiro; Ding, Qiang; Miyazaki, Yumi; Kuwahata, Taisaku; Tsukasa, Koichiro; Takao, Sonshin

    2013-11-01

    Pancreatic cancer is characterized by near-universal mutations in KRAS. The mammalian target of rapamycin (mTOR), which functions downstream of RAS, has divergent effects on stem cells. In the present study, we investigated the significance of the mTOR pathway in maintaining the properties of pancreatic cancer stem cells. The mTOR inhibitor, rapamycin, reduced the viability of CD133+ pancreatic cancer cells and sphere formation which is an index of self-renewal of stem-like cells, indicating that the mTOR pathway functions to maintain cancer stem-like cells. Further, rapamycin had different effects on CD133+ cells compared to cyclopamine which is an inhibitor of the Hedgehog pathway. Thus, the mTOR pathway has a distinct role although both pathways maintain pancreatic cancer stem cells. Therefore, mTOR might be a promising target to eliminate pancreatic cancer stem cells.

  16. Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels.

    PubMed

    Uzunalli, Gozde; Tumtas, Yasin; Delibasi, Tuncay; Yasa, Oncay; Mercan, Sercan; Guler, Mustafa O; Tekinay, Ayse B

    2015-08-01

    Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel networks. Thus, it is important to provide a proper mechanically and biologically supportive environment for enhancing both in vitro islet culture and transplantation efficiency. Here, we demonstrate that heparin mimetic peptide amphiphile (HM-PA) nanofibrous network is a promising platform for these purposes. The islets cultured with peptide nanofiber gel containing growth factors exhibited a similar glucose stimulation index as that of the freshly isolated islets even after 7 days. After transplantation of islets to STZ-induced diabetic rats, 28 day-long monitoring displayed that islets that were transplanted in HM-PA nanofiber gels maintained better blood glucose levels at normal levels compared to the only islet transplantation group. In addition, intraperitoneal glucose tolerance test revealed that animals that were transplanted with islets within peptide gels showed a similar pattern with the healthy control group. Histological assessment showed that islets transplanted within peptide nanofiber gels demonstrated better islet integrity due to increased blood vessel density. This work demonstrates that using the HM-PA nanofiber gel platform enhances the islets function and islet transplantation efficiency both in vitro and in vivo. PMID:25931015

  17. Imaging Tests for the Diagnosis and Staging of Pancreatic Adenocarcinoma: A Meta-Analysis.

    PubMed

    Treadwell, Jonathan R; Zafar, Hanna M; Mitchell, Matthew D; Tipton, Kelley; Teitelbaum, Ursina; Jue, Jane

    2016-07-01

    Imaging tests are central to the diagnosis and staging of pancreatic adenocarcinoma. We performed a systematic review and meta-analysis of the pertinent evidence on 5 imaging tests (computed tomography (CT), magnetic resonance imaging, CT angiography, endoscopic ultrasound with fine-needle aspiration, and combined positron emission tomography with CT). Searches of several databases up to March 1, 2014, yielded 9776 articles, and 24 provided comparative effectiveness of 2 or more imaging tests. Multiple reviewers applied study inclusion criteria, extracted data from each study, rated the risk of bias, and graded the strength of evidence. Data included accuracy of diagnosis and resectability in primary untreated pancreatic adenocarcinoma, including tumor stage, nodal stage, metastases, and vascular involvement. Where possible, study results were combined using bivariate meta-analysis. Studies were at low or moderate risk of bias. Most comparisons between imaging tests were insufficient to permit conclusions, due to imprecision or inconsistency among study results. However, moderate-grade evidence revealed that CT and magnetic resonance imaging had similar sensitivities and specificities for both diagnosis and vascular involvement. Other conclusions were based on low-grade evidence. In general, more direct evidence is needed to inform decisions about imaging tests for pancreatic adenocarcinoma. PMID:26745859

  18. Pancreatic and Islet Development and Function: The Role of Thyroid Hormone

    PubMed Central

    Mastracci, Teresa L; Evans-Molina, Carmella

    2014-01-01

    A gradually expanding body of literature suggests that Thyroid Hormone (TH) and Thyroid Hormone Receptors (TRs) play a contributing role in pancreatic and islet cell development, maturation, and function. Studies using a variety of model systems capable of exploiting species-specific developmental paradigms have revealed the contribution of TH to cellular differentiation, lineage decisions, and endocrine cell specification. Moreover, in vitro and in vivo evidence suggests that TH is involved in islet β cell proliferation and maturation; however, the signaling pathway(s) connected with this function of TH/TR are not well understood. The purpose of this review is to discuss the current literature that has defined the effects of TH and TRs on pancreatic and islet cell development and function, describe the impact of hyper- and hypothyroidism on whole body metabolism, and highlight future and potential applications of TH in novel therapeutic strategies for diabetes. PMID:25506600

  19. A scalable system for production of functional pancreatic progenitors from human embryonic stem cells.

    PubMed

    Schulz, Thomas C; Young, Holly Y; Agulnick, Alan D; Babin, M Josephine; Baetge, Emmanuel E; Bang, Anne G; Bhoumik, Anindita; Cepa, Igor; Cesario, Rosemary M; Haakmeester, Carl; Kadoya, Kuniko; Kelly, Jonathan R; Kerr, Justin; Martinson, Laura A; McLean, Amanda B; Moorman, Mark A; Payne, Janice K; Richardson, Mike; Ross, Kelly G; Sherrer, Eric S; Song, Xuehong; Wilson, Alistair Z; Brandon, Eugene P; Green, Chad E; Kroon, Evert J; Kelly, Olivia G; D'Amour, Kevin A; Robins, Allan J

    2012-01-01

    Development of a human embryonic stem cell (hESC)-based therapy for type 1 diabetes will require the translation of proof-of-principle concepts into a scalable, controlled, and regulated cell manufacturing process. We have previously demonstrated that hESC can be directed to differentiate into pancreatic progenitors that mature into functional glucose-responsive, insulin-secreting cells in vivo. In this study we describe hESC expansion and banking methods and a suspension-based differentiation system, which together underpin an integrated scalable manufacturing process for producing pancreatic progenitors. This system has been optimized for the CyT49 cell line. Accordingly, qualified large-scale single-cell master and working cGMP cell banks of CyT49 have been generated to provide a virtually unlimited starting resource for manufacturing. Upon thaw from these banks, we expanded CyT49 for two weeks in an adherent culture format that achieves 50-100 fold expansion per week. Undifferentiated CyT49 were then aggregated into clusters in dynamic rotational suspension culture, followed by differentiation en masse for two weeks with a four-stage protocol. Numerous scaled differentiation runs generated reproducible and defined population compositions highly enriched for pancreatic cell lineages, as shown by examining mRNA expression at each stage of differentiation and flow cytometry of the final population. Islet-like tissue containing glucose-responsive, insulin-secreting cells was generated upon implantation into mice. By four- to five-months post-engraftment, mature neo-pancreatic tissue was sufficient to protect against streptozotocin (STZ)-induced hyperglycemia. In summary, we have developed a tractable manufacturing process for the generation of functional pancreatic progenitors from hESC on a scale amenable to clinical entry. PMID:22623968

  20. Thyroid Function Tests.

    ERIC Educational Resources Information Center

    Glover, Irving T.

    1979-01-01

    Describes two tests, T-4 and T-3, for hypothyroid based on the binding of the hormones by proteins. The tests were performed in courses for physicians, clinical chemists, laboratory technicians, and undergraduate science students by the individuals involved and on their own sera. These tests are commercially available in kit form. (GA)

  1. Cloning and functional expression of a human pancreatic islet glucose-transporter cDNA

    SciTech Connect

    Permutt, M.A.; Koranyi, L.; Keller, K.; Lacy, P.E.; Scharp, D.W.; Mueckler, M. )

    1989-11-01

    Previous studies have suggested that pancreatic islet glucose transport is mediated by a high-K{sub m}, low-affinity facilitated transporter similar to that expressed in liver. To determine the relationship between islet and liver glucose transporters, liver-type glucose-transporter cDNA clones were isolated from a human liver cDNA library. The liver-type glucose-transporter cDNA clone hybridized to mRNA transcripts of the same size in human liver and pancreatic islet RNA. A cDNA library was prepared from purified human pancreatic islet tissue and screened with human liver-type glucose-transporter cDNA. The authors isolated two overlapping cDNA clones encompassing 2600 base pairs, which encode a pancreatic islet protein identical in sequence to that of the putative liver-type glucose-transporter protein. Xenopus oocytes injected with synthetic mRNA transcribed from a full-length cDNA construct exhibited increased uptake of 2-deoxyglucose, confirming the functional identity of the clone. These cDNA clones can now be used to study regulation of expression of the gene and to assess the role of inherited defects in this gene as a candidate for inherited susceptibility to non-insulin-dependent diabetes mellitus.

  2. Secretome analysis of multiple pancreatic cancer cell lines reveals perturbations of key functional networks.

    PubMed

    Schiarea, Silvia; Solinas, Graziella; Allavena, Paola; Scigliuolo, Graziana Maria; Bagnati, Renzo; Fanelli, Roberto; Chiabrando, Chiara

    2010-09-01

    The cancer secretome is a rich repository in which to mine useful information for both cancer biology and clinical oncology. To help understand the mechanisms underlying the progression of pancreatic cancer, we characterized the secretomes of four human pancreatic ductal adenocarcinoma (PDAC) cell lines versus a normal counterpart. To this end, we used a proteomic workflow based on high-confidence protein identification by mass spectrometry, semiquantitation by a label-free approach, and network enrichment analysis by a system biology tool. Functional networks significantly enriched with PDAC-dysregulated proteins included not only expected alterations within key mechanisms known to be relevant for tumor progression (e.g., cell-cell/cell-matrix adhesion, extracellular matrix remodeling, and cytoskeleton rearrangement), but also other extensive, coordinated perturbations never observed in pancreatic cancer. In particular, we highlighted perturbations possibly favoring tumor progression through immune escape (i.e., inhibition of the complement system, deficiency of selected proteasome components within the antigen-presentation machinery, and inhibition of T cell cytoxicity), and a defective protein folding machinery. Among the proteins found concordantly oversecreted in all of our PDAC cell lines, many are reportedly overexpressed in pancreatic cancer (e.g., CD9 and Vimentin), while others (PLOD3, SH3L3, PCBP1, and SFRS1) represent novel PDAC-secreted proteins that may be worth investigating. PMID:20687567

  3. Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro

    PubMed Central

    Russ, Holger A; Parent, Audrey V; Ringler, Jennifer J; Hennings, Thomas G; Nair, Gopika G; Shveygert, Mayya; Guo, Tingxia; Puri, Sapna; Haataja, Leena; Cirulli, Vincenzo; Blelloch, Robert; Szot, Greg L; Arvan, Peter; Hebrok, Matthias

    2015-01-01

    Directed differentiation of human pluripotent stem cells into functional insulin-producing beta-like cells holds great promise for cell replacement therapy for patients suffering from diabetes. This approach also offers the unique opportunity to study otherwise inaccessible aspects of human beta cell development and function in vitro. Here, we show that current pancreatic progenitor differentiation protocols promote precocious endocrine commitment, ultimately resulting in the generation of non-functional polyhormonal cells. Omission of commonly used BMP inhibitors during pancreatic specification prevents precocious endocrine formation while treatment with retinoic acid followed by combined EGF/KGF efficiently generates both PDX1+ and subsequent PDX1+/NKX6.1+ pancreatic progenitor populations, respectively. Precise temporal activation of endocrine differentiation in PDX1+/NKX6.1+ progenitors produces glucose-responsive beta-like cells in vitro that exhibit key features of bona fide human beta cells, remain functional after short-term transplantation, and reduce blood glucose levels in diabetic mice. Thus, our simplified and scalable system accurately recapitulates key steps of human pancreas development and provides a fast and reproducible supply of functional human beta-like cells. PMID:25908839

  4. High Intensity Interval Training Improves Glycaemic Control and Pancreatic β Cell Function of Type 2 Diabetes Patients

    PubMed Central

    Madsen, Søren Møller; Thorup, Anne Cathrine; Overgaard, Kristian; Jeppesen, Per Bendix

    2015-01-01

    Physical activity improves the regulation of glucose homeostasis in both type 2 diabetes (T2D) patients and healthy individuals, but the effect on pancreatic β cell function is unknown. We investigated glycaemic control, pancreatic function and total fat mass before and after 8 weeks of low volume high intensity interval training (HIIT) on cycle ergometer in T2D patients and matched healthy control individuals. Study design/method: Elderly (56 yrs±2), non-active T2D patients (n = 10) and matched (52 yrs±2) healthy controls (CON) (n = 13) exercised 3 times (10×60 sec. HIIT) a week over an 8 week period on a cycle ergometer. Participants underwent a 2-hour oral glucose tolerance test (OGTT). On a separate day, resting blood pressure measurement was conducted followed by an incremental maximal oxygen uptake (V˙O2max) cycle ergometer test. Finally, a whole body dual X-ray absorptiometry (DXA) was performed. After 8 weeks of training, the same measurements were performed. Results: in the T2D-group, glycaemic control as determined by average fasting venous glucose concentration (p = 0.01), end point 2-hour OGTT (p = 0.04) and glycosylated haemoglobin (p = 0.04) were significantly reduced. Pancreatic homeostasis as determined by homeostatic model assessment of insulin resistance (HOMA-IR) and HOMA β cell function (HOMA-%β) were both significantly ameliorated (p = 0.03 and p = 0.03, respectively). Whole body insulin sensitivity as determined by the disposition index (DI) was significantly increased (p = 0.03). During OGTT, the glucose continuum was significantly reduced at -15 (p = 0.03), 30 (p = 0.03) and 120 min (p = 0.03) and at -10 (p = 0.003) and 0 min (p = 0.003) with an additional improvement (p = 0.03) of its 1st phase (30 min) area under curve (AUC). Significant abdominal fat mass losses were seen in both groups (T2D: p = 0.004 and CON: p = 0.02) corresponding to a percentage change of -17.84%±5.02 and -9.66%±3.07, respectively. Conclusion: these results

  5. Glucoregulatory function of thyroid hormones: role of pancreatic hormones

    SciTech Connect

    Mueller, M.J.B.; Burger, A.G.; Ferrannini, E.; Jequier, E.; Acheson, K.J.

    1989-01-01

    Glucose metabolism was investigated in humans before and 14 days after 300 micrograms L-thyroxine (T4)/day using a sequential clamp protocol during short-term somatostatin infusion (500 micrograms/h, 0-6 h) at euglycemia (0-2.5 h), at 165 mg/dl (2.5-6 h), and during insulin infusion (1.0 mU.kg-1.min-1, 4.5-6 h). T4 treatment increased plasma T4 (+96%) and 3,5,3'-triiodothyronine (T3, +50%), energy expenditure (+8%), glucose turnover (+32%), and glucose oxidation (Glucox +87%) but decreased thyroid-stimulating hormone (-96%) and nonoxidative glucose metabolism (Glucnonox, -30%) at unchanged lipid oxidation (Lipox). During somatostatin and euglycemia glucose production (Ra, -67%) and disposal (Rd, -28%) both decreased in euthyroid subjects but remained at -22% and -5%, respectively, after T4 treatment. Glucox (control, -20%; +T4, -25%) fell and Lipox increased (control, +42%; +T4, +45%) in both groups, whereas Glucnonox decreased before (-36%) but increased after T4 (+57%). During somatostatin infusion and hyperglycemia Rd (control, +144%; +T4, +84%) and Glucnonox (control, +326%; +T4, +233%) increased, whereas Glucox and Lipox remained unchanged. Insulin further increased Rd (+76%), Glucox (+155%), and Glucnonox (+50%) but decreased Ra (-43%) and Lipox (-43%). All these effects were enhanced by T4 (Rd, +38%; Glucox, +45%; Glucnonox, +35%; Ra, +40%; Lipox, +11%). Our data provide evidence that, in humans, T3 stimulates Ra and Rd, which is in part independent of pancreatic hormones.

  6. Emodin enhances alveolar epithelial barrier function in rats with experimental acute pancreatitis

    PubMed Central

    Xia, Xian-Ming; Wang, Fang-Yu; Wang, Zhen-Kai; Wan, Hai-Jun; Xu, Wen-An; Lu, Heng

    2010-01-01

    claudin-4, claudin-5 and occluding was increased, and the pulmonary dye extravasation was reduced in lung tissue samples from rats with acute pancreatitis after treatment with emodin. CONCLUSION: Emodin attenuates pulmonary edema and inflammation, enhances alveolar epithelial barrier function, and promotes expression of claudin-4, claudin-5 and occludin in lung tissue samples from rats with acute pancreatitis. PMID:20572302

  7. Pulmonary Function Tests

    MedlinePlus

    ... enters your body. The most common PFT’s are spirometry (spy-RAH-me-tree), diffusion studies and body ... on the day of your test. What is spirometry? Spirometry is one of the most commonly ordered ...

  8. Thyroid function tests

    MedlinePlus

    ... free T4 (the main thyroid hormone in your blood) TSH (the hormone from the pituitary gland that stimulates the thyroid to produce T4) T3 (also included sometimes) Other thyroid tests include: T3 resin uptake Thyroid scan

  9. Chronic pancreatitis

    MedlinePlus

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  10. Acute pancreatitis

    MedlinePlus

    ... rate Lab tests that show the release of pancreatic enzymes will be done. These include: Increased blood amylase level Increased serum blood lipase level Increased urine amylase ... include: Abdominal CT scan Abdominal MRI Abdominal ultrasound

  11. [Endothelial function test].

    PubMed

    Tomiyama, Hirofumi

    2015-11-01

    Endothelial dysfunction is thought to have pivotal roles for the development of hypertension, initiation/progression of hypertensive organ damages, and prognosis. In clinical setting, flow-mediated vasodilatation (FMD) of brachial artery is used as a marker of endothelial function. However, well-trained sonographer is needed to conduct FMD measurement, and therefore, FMD has not been fully standardized (i.e., the reference value of FMD has not been established). Even so, FMD predicts future cardiovascular events. Lifestyle modifications (i.e., smoking cessation, exercise, or weight loss) and antihypertensive medication provide beneficial effects on endothelial function. Thus, FMD have a potential as a useful surrogate marker for the management of hypertension. PMID:26619655

  12. Mechanisms of CFTR Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis

    PubMed Central

    Lewis, Michele D.; Park, Hyun Woo; Brand, Randall E.; Gelrud, Andres; Anderson, Michelle A.; Banks, Peter A.; Conwell, Darwin; Lawrence, Christopher; Romagnuolo, Joseph; Baillie, John; Alkaade, Samer; Cote, Gregory; Gardner, Timothy B.; Amann, Stephen T.; Slivka, Adam; Sandhu, Bimaljit; Aloe, Amy; Kienholz, Michelle L.; Yadav, Dhiraj; Barmada, M. Michael; Bahar, Ivet; Lee, Min Goo; Whitcomb, David C.

    2014-01-01

    CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens) but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a) screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b) conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c) computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d) tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N) not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002). Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005) and male infertility (OR 395, p<<0.0001). WNK1-SPAK pathway-activated increases in CFTR

  13. ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function

    SciTech Connect

    Pi Jingbo; Zhang Qiang; Fu Jingqi; Woods, Courtney G.; Hou Yongyong; Corkey, Barbara E.; Collins, Sheila; Andersen, Melvin E.

    2010-04-01

    This review focuses on the emerging evidence that reactive oxygen species (ROS) derived from glucose metabolism, such as H{sub 2}O{sub 2}, act as metabolic signaling molecules for glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. Particular emphasis is placed on the potential inhibitory role of endogenous antioxidants, which rise in response to oxidative stress, in glucose-triggered ROS and GSIS. We propose that cellular adaptive response to oxidative stress challenge, such as nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant induction, plays paradoxical roles in pancreatic beta-cell function. On the one hand, induction of antioxidant enzymes protects beta-cells from oxidative damage and possible cell death, thus minimizing oxidative damage-related impairment of insulin secretion. On the other hand, the induction of antioxidant enzymes by Nrf2 activation blunts glucose-triggered ROS signaling, thus resulting in reduced GSIS. These two premises are potentially relevant to impairment of beta-cells occurring in the late and early stage of Type 2 diabetes, respectively. In addition, we summarized our recent findings that persistent oxidative stress due to absence of uncoupling protein 2 activates cellular adaptive response which is associated with impaired pancreatic beta-cell function.

  14. Pulmonary Function Testing in Children

    MedlinePlus

    ... are s pirometry and airway resistance tests . What is spirometry? Spirometry is the most common lung function test done. ... follow very specific instructions. Most children can do spirometry by age 6, though some preschoolers are able ...

  15. The expression and function of histamine H3 receptors in pancreatic beta cells

    PubMed Central

    Nakamura, T; Yoshikawa, T; Noguchi, N; Sugawara, A; Kasajima, A; Sasano, H; Yanai, K

    2014-01-01

    BACKGROUND AND PURPOSE Histamine and its receptors in the CNS play important roles in energy homeostasis. Here, we have investigated the expression and role of histamine receptors in pancreatic beta cells, which secrete insulin. EXPERIMENTAL APPROACH The expression of histamine receptors in pancreatic beta cells was examined by RT-PCR, Western blotting and immunostaining. Insulin secretion assay, ATP measurement and calcium imaging studies were performed to determine the function and signalling pathway of histamine H3 receptors in glucose-induced insulin secretion (GIIS) from MIN6 cells, a mouse pancreatic beta cell line. The function and signalling pathway of H3 receptors in MIN6 cell proliferation were examined using pharmacological assay and Western blotting. KEY RESULTS Histamine H3 receptors were expressed in pancreatic beta cells. A selective H3 receptor agonist, imetit, and a selective inverse H3 receptor agonist, JNJ-5207852, had inhibitory and facilitatory effects, respectively, on GIIS in MIN6 cells. Neither imetit nor JNJ-5207852 altered intracellular ATP concentration, or intracellular calcium concentration stimulated by glucose and KCl, indicating that GIIS signalling was affected by H3 receptor signalling downstream of the increase in intracellular calcium concentration. Moreover, imetit attenuated bromodeoxyuridine incorporation in MIN6 cells. The phosphorylation of cAMP response element-binding protein (CREB), which facilitated beta cell proliferation, was inhibited, though not significantly, by imetit, indicating that activated H3 receptors inhibited MIN6 cell proliferation, possibly by decreasing CREB phosphorylation. CONCLUSIONS AND IMPLICATIONS Histamine H3 receptors were expressed in mouse beta cells and could play a role in insulin secretion and, possibly, beta cell proliferation. PMID:24117016

  16. [Aspartame--the sweet-tasting dipeptide--does not affect the pancreatic insulin-secreting function].

    PubMed

    Sadovnikova, N V; Fedotov, V P; Aleshina, L V; Shvachkin, Iu P; Girin, S K

    1984-01-01

    The action of a synthetic dipeptide aspartam (150 to 180 times as sweet as glucose) on pancreatic insulin-secretory function of rats was studied in vivo and in vitro. The drug was given orally while drinking (300 mg/kg body weight) or was added to the incubation medium of cultivated pancreatic cells (20 mM). It was shown that insulin content in the rat blood serum remained unchanged 10 and 35 minutes after aspartam administration. The drug did not exert any stimulating effect upon insulin secretion following the addition to the pancreatic cell culture medium. It is concluded that aspartam exhibits no direct or mediated action on pancreatic insulin-secretory function. PMID:6382247

  17. Function of transplanted human pancreatic allografts after preservation in cold storage for 6 to 26 hours.

    PubMed

    Abouna, G M; Sutherland, D E; Florack, G; Najarian, J S

    1987-05-01

    Preservation of cadaveric pancreas allografts has been a difficult problem in clinical pancreas transplantation; most institutions use Collins solution and limit preservation time to less than 6 hr. Longer preservation times have been used at the University of Minnesota. Between August 1983, and December 1985, 47 human cadaveric pancreas grafts were transplanted into Type I diabetic recipients after cold storage at 4 degrees C in a modified, hyperosmolar silica-gel filtered plasma (SGFP), a solution previously found to allow dog pancreas grafts to be successfully preserved for up to 48 hr. Ten grafts were preserved for 2-5 hr (group 1); 20 for 6-11 hr (group 2; 17 for 12-26 hr (group 3). Graft function and late outcome were compared between these groups and another group of 7 cadaveric grafts (group 4), which were transplanted immediately and without any preservation. Analysis of exocrine pancreatic function early after transplantation showed a maximum mean serum amylase (IU/L) of 557, 440, 429, and 307 in groups 1, 2, 3, and 4, respectively. Primary preservation failure rates of 0, 5%, 5.8%, and 0%, and endocrine graft function rates at 1 month of 80%, 80%, 76%, and 86% were obtained for groups 1, 2, 3, and 4, respectively (P = NS). Only patients who were insulin-independent were counted as having functioning grafts. Detailed functional studies at 1 month showed that mean plasma glucose levels during 24-hr metabolic profiles were in the normal range in 71%, 68%, 72%, and 50%, while oral glucose tolerance test results were within the normal range in 38%, 81%, 76%, and 66% of groups 1, 2, 3, and 4, respectively (P = NS). At 1 year, patient survival rates were 57%, 88%, 75%, and 100% (P = NS), and the graft functional survival rates were 0, 25%, 33%, and 29% (P = NS) in the respective groups. Five patients in group 2, and 6 in group 3 have currently functioning grafts at 4 to 37 months after transplantation. We conclude that cadaver pancreas grafts can be safely

  18. [COMPARATIVE EVALUATION OF THE EFFECTIVENESS OF THE USE OF 13C-LABELED MIXED TRIGLYCERIDE AND 13C-STARCH BREATH TESTS IN PATIENTS WITH CHRONIC PANCREATITIS AFTER CHOLECYSTECTOMY].

    PubMed

    Sirchak, Ye S

    2015-01-01

    The results of a comprehensive study of 96 patients after cholecystectomy are provided. The higher sensitivity and informativeness of the 13C-labeled mixed triglyceride breath .test compared with 13C-starch breath test for determining functional pancreatic insufficiency in patients after cholecystectomy in early stages of its formation was set. PMID:27491156

  19. Transcriptional Regulation of the Pancreatic Islet: Implications for Islet Function

    PubMed Central

    Stitzel, Michael L.; Kycia, Ina; Kursawe, Romy; Ucar, Duygu

    2015-01-01

    Islets of Langerhans contain multiple hormone-producing endocrine cells controlling glucose homeostasis. Transcription establishes and maintains islet cellular fates and identities. Genetic and environmental disruption of islet transcription triggers cellular dysfunction and disease. Early transcriptional regulation studies of specific islet genes, including insulin (INS) and the transcription factor PDX1, identified the first cis-regulatory DNA sequences and trans-acting factors governing islet function. Here, we review how human islet “omics” studies are reshaping our understanding of transcriptional regulation in islet (dys)function and diabetes. First, we highlight the expansion of islet transcript number, form, and function and of DNA transcriptional regulatory elements controlling their production. Next, we cover islet transcriptional effects of genetic and environmental perturbation. Finally, we discuss how these studies’ emerging insights should empower our diabetes research community to build mechanistic understanding of diabetes pathophysiology and to equip clinicians with tailored, precision medicine options to prevent and treat islet dysfunction and diabetes. PMID:26272056

  20. [Change in pancreatic exocrine function in acute appendicitis].

    PubMed

    Ivanov, Iu A

    1979-10-01

    In order to study changes in the functional state of the pancreas 1572 investigations of the blood and urine amylase, atoxylresistant lipase of the blood serum before operation were performed in different postoperative periods in 131 patients with acute appendicitis. The enzyme activity was established to increase, especially in destructive forms of appendicitis and in elderly patients. PMID:505800

  1. Tests of gastric neuromuscular function.

    PubMed

    Parkman, Henry P; Jones, Michael P

    2009-05-01

    Tests of gastric neuromuscular function are used to evaluate patients with symptoms referable to the upper digestive tract. These symptoms can be associated with alterations in the rates of gastric emptying, impaired accommodation, heightened gastric sensation, or alterations in gastric myoelectrical function and contractility. Management of gastric neuromuscular disorders requires an understanding of pathophysiology and treatment options as well as the appropriate use and interpretation of diagnostic tests. These tests include measures of gastric emptying; contractility; electrical activity; regional gastric motility of the fundus, antrum, and pylorus; and tests of sensation and compliance. Tests are also being developed to improve our understanding of the afferent sensory pathways from the stomach to the central nervous system that mediate gastric sensation in health and gastric disorders. This article reviews tests of gastric function and provides a basic description of the tests, the methodologies behind them, descriptions of the physiology that they assess, and their clinical utility. PMID:19293005

  2. Cathelicidins positively regulate pancreatic β-cell functions.

    PubMed

    Sun, Jia; Xu, Meng; Ortsäter, Henrik; Lundeberg, Erik; Juntti-Berggren, Lisa; Chen, Yong Q; Haeggström, Jesper Z; Gudmundsson, Gudmundur H; Diana, Julien; Agerberth, Birgitta

    2016-02-01

    Cathelicidins are pleiotropic antimicrobial peptides largely described for innate antimicrobial defenses and, more recently, immunomodulation. They are shown to modulate a variety of immune or nonimmune host cell responses. However, how cathelicidins are expressed by β cells and modulate β-cell functions under steady-state or proinflammatory conditions are unknown. We find that cathelicidin-related antimicrobial peptide (CRAMP) is constitutively expressed by rat insulinoma β-cell clone INS-1 832/13. CRAMP expression is inducible by butyrate or phenylbutyric acid and its secretion triggered upon inflammatory challenges by IL-1β or LPS. CRAMP promotes β-cell survival in vitro via the epidermal growth factor receptor (EGFR) and by modulating expression of antiapoptotic Bcl-2 family proteins: p-Bad, Bcl-2, and Bcl-xL. Also via EGFR, CRAMP stimulates glucose-stimulated insulin secretion ex vivo by rat islets. A similar effect is observed in diabetes-prone nonobese diabetic (NOD) mice. Additional investigation under inflammatory conditions reveals that CRAMP modulates inflammatory responses and β-cell apoptosis, as measured by prostaglandin E2 production, cyclooxygenases (COXs), and caspase activation. Finally, CRAMP-deficient cnlp(-/-) mice exhibit defective insulin secretion, and administration of CRAMP to prediabetic NOD mice improves blood glucose clearance upon glucose challenge. Our finding suggests that cathelicidins positively regulate β-cell functions and may be potentially used for intervening β-cell dysfunction-associated diseases. PMID:26527065

  3. Age-Dependent Pancreatic Gene Regulation Reveals Mechanisms Governing Human β Cell Function.

    PubMed

    Arda, H Efsun; Li, Lingyu; Tsai, Jennifer; Torre, Eduardo A; Rosli, Yenny; Peiris, Heshan; Spitale, Robert C; Dai, Chunhua; Gu, Xueying; Qu, Kun; Wang, Pei; Wang, Jing; Grompe, Markus; Scharfmann, Raphael; Snyder, Michael S; Bottino, Rita; Powers, Alvin C; Chang, Howard Y; Kim, Seung K

    2016-05-10

    Intensive efforts are focused on identifying regulators of human pancreatic islet cell growth and maturation to accelerate development of therapies for diabetes. After birth, islet cell growth and function are dynamically regulated; however, establishing these age-dependent changes in humans has been challenging. Here, we describe a multimodal strategy for isolating pancreatic endocrine and exocrine cells from children and adults to identify age-dependent gene expression and chromatin changes on a genomic scale. These profiles revealed distinct proliferative and functional states of islet α cells or β cells and histone modifications underlying age-dependent gene expression changes. Expression of SIX2 and SIX3, transcription factors without prior known functions in the pancreas and linked to fasting hyperglycemia risk, increased with age specifically in human islet β cells. SIX2 and SIX3 were sufficient to enhance insulin content or secretion in immature β cells. Our work provides a unique resource to study human-specific regulators of islet cell maturation and function. PMID:27133132

  4. Mass Spectrometry-Based Proteomics of Endoscopically-Collected Pancreatic Fluid in Chronic Pancreatitis Research

    PubMed Central

    Paulo, Joao A.; Lee, Linda S.; Wu, Bechien; Banks, Peter A.; Steen, Hanno; Conwell, Darwin L.

    2011-01-01

    Mass spectrometry-based investigation of pancreatic fluid enables the high-throughput identification of proteins present in the pancreatic secretome. Pancreatic fluid is a complex admixture of digestive, inflammatory, and other proteins secreted by the pancreas into the duodenum, and thus is amenable to mass spectrometry-based proteomic analysis. Recent advances in endoscopic techniques, in particular the endoscopic pancreatic function test (ePFT), have improved the collection methodology of pancreatic fluid for proteomic analysis. Here, we provide an overview of mass spectrometry-based proteomic techniques as applied to the study of pancreatic fluid. We address sample collection, protein extraction, mass spectrometry sample preparation and analysis, and bioinformatic approaches and summarize current mass spectrometry-based investigations of pancreatic fluid. We then examine the limitations and the future potential of such technologies in the investigation of pancreatic disease. We conclude that pancreatic fluid represents a rich reservoir of potential biomarkers and that the study of the molecular mechanisms of chronic pancreatitis may benefit substantially from mass spectrometry-based proteomics. PMID:21360826

  5. Pancreatitis - discharge

    MedlinePlus

    Chronic pancreatitis - discharge; Pancreatitis - chronic - discharge; Pancreatic insufficiency - discharge; Acute pancreatitis - discharge ... You were in the hospital because you have pancreatitis. This is a swelling of the pancreas. You ...

  6. [Chronic elevation of enzymes of pancreatic origin in asymptomatic patients].

    PubMed

    Quílez, C; Martínez, J; Gómez, A; Trigo, C; Palazón, J M; Belda, G; Pérez-Mateo, M

    1998-05-01

    Chronic asymptomatic elevation of pancreatic enzymes is a well known entity although little has been reported. In most cases chronic asymptomatic elevation of amylase is due to a salival isoamylase increase or macroamylasemia. However, we have studied 10 cases with an increase in amylases due to pancreatic isoamylase and an increase in the remaining pancreatic enzymes which remained elevated during the follow up period ranging from 2 to 60 months. The amylase values ranged from 186 to 1,600; the lipase from 176 to 3,989, trypsin from 476 to 2,430 and pancreatic isoamylase from 122 to 1,263. In all patients CT and echography were carried out, which discarded structural damage. Nonetheless, an indirect test of pancreatic function presented unexplained pathologic values in 4 out of 10 patients. In conclusion, we suggest that chronic asymptomatic elevation of pancreatic enzymes is of unknown etiology with no associated structural pancreatic pathology demonstrable by the usual study methods. PMID:9644872

  7. Prognostic and Functional Significance of MAP4K5 in Pancreatic Cancer

    PubMed Central

    Wang, Oliver H.; Azizian, Nancy; Guo, Ming; Capello, Michela; Deng, Defeng; Zang, Fenglin; Fry, Jason; Katz, Matthew H.; Fleming, Jason B.; Lee, Jeffrey E.; Wolff, Robert A.; Hanash, Samir; Wang, Huamin; Maitra, Anirban

    2016-01-01

    Objectives MAP4K5 plays an important role in regulating a range of cellular responses and is involved in Wnt signaling in hematopoietic cells. However, its functions in human malignancies have not been studied. The major objectives of this study are to examine the expression, functions and clinical significance of MAP4K5 in pancreatic ductal adenocarcinoma (PDAC). Materials and Methods The expression levels of MAP4K5, E-cadherin, vimentin, and carboxylesterase 2 (CES2) were examined by immunohistochemistry in 105 PDAC and matched non-neoplastic pancreas samples from our institution. The RNA sequencing data of 112 PDAC patients were downloaded from the TCGA data portal. Immunoblotting and RNA sequencing analysis were used to examine the expression of MAP4K5 and E-cadherin in pancreatic cancer cell lines. The effect of knockdown MAP4K5 using siRNA on the expression of CDH1 and vimentin were examined by Real-time RT-PCR in Panc-1 and AsPC-1 cells. Statistical analyses were performed using IBM SPSS Statistics. Results MAP4K5 protein is expressed at high levels specifically in the pancreatic ductal cells of 100% non-neoplastic pancreas samples, but is decreased or lost in 77.1% (81/105) of PDAC samples. MAP4K5-low correlated with the loss of E-cadherin (P = 0.001) and reduced CES2 expression (P = 0.002) in our patient populations. The expression levels of MAP4K5 mRNA directly correlated with the expression levels of CDH1 mRNA (R = 0.2490, P = 0.008) in the second cohort of 112 PDAC patients from The Cancer Genome Atlas (TCGA) RNA-seq dataset. Similar correlations between the expression of MAP4K5 and E-cadherin were observed both at protein and mRNA levels in multiple pancreatic cancer cell lines. Knockdown MAP4K5 led to decreased CDH1 mRNA expression in Panc-1 and AsPC-1 cells. MAP4K5-low correlated significantly with reduced overall survival and was an independent prognosticator in patients with stage II PDAC. Conclusions MAP4K5 expression is decreased or lost in

  8. Preoperative cognitive function predicts survival in patients with resectable pancreatic ductal adenocarcinoma

    PubMed Central

    Baekelandt, Bart M.G.; Hjermstad, Marianne J.; Nordby, Tom; Fagerland, Morten W.; Kure, Elin H.; Heiberg, Turid; Buanes, Trond; Labori, Knut J.

    2015-01-01

    Background The purpose of this prospective study was to evaluate whether pre-surgery health-related quality of life (HRQoL) and subjectively rated symptom scores are prognostic factors for survival in patients with resectable pancreatic ductal adenocarcinoma (PDAC). Methods Patients undergoing pancreatic resection for PDAC completed the Edmonton Symptom Assessment System (ESAS) and the EORTC QLQ-C30 and QLQ-PAN26 questionnaires preoperatively. Patient, tumor and treatment characteristics, recurrence and survival were registered. Results Sixty-six consecutive patients underwent R0/R1 resection for PDAC. Baseline ESAS and EORTC questionnaire compliance was 44/66 (67%) with no statistically significant differences between compliers (n = 44) and non-compliers (n = 22) when comparing clinicopathological parameters and survival. Univariable analyses showed that three symptoms (nausea, dry mouth, cognitive function) and two clinicopathological factors (CA 19-9 > 400 U/ml, lymph node ratio > 0.1) were significantly associated with shorter survival (p < 0.05). In multivariable analysis, cognitive function was the only independent predictor for survival: hazard ratio = 0.35 (95%CI 0.13–0.93) for high vs low cognitive function. Median survival times for patients with high and low cognitive function were 21 and 10 months, respectively (p < 0.001). Conclusion Presurgery cognitive function is a significant independent predictor of survival in patients with resectable PDAC. Thus, presurgery patient reported outcomes may provide as strong prognostic information as clinicopathological factors. PMID:27017164

  9. Pancreatic panniculitis associated with pancreatic carcinoma

    PubMed Central

    Zhang, Guannan; Cao, Zhe; Yang, Gang; Wu, Wenming; Zhang, Taiping; Zhao, Yupei

    2016-01-01

    Abstract Introduction: Pancreatic panniculitis is a very rare complication of pancreatic cancer, most often accompanying rare acinar cell carcinoma. We herein report a case of pancreatic panniculitis that was associated with pancreatic mucinous adenocarcinoma. Patient information: A 57-year-old male was referred to our hospital for weight loss. A physical examination revealed subcutaneous nodules on his lower extremities. The blood test showed abnormal increases in amylase, lipase, and carbohydrate antigen 19–9 levels. A computed tomography scan detected a hypodense 2 × 1.5 cm solid mass with an unclear margin in the head of the pancreas. The biopsy of subcutaneous nodules on the lower extremities was conducted and revealed lobular panniculitis. Pancreatic cancer and pancreatic panniculitis were strongly suspected. After the administration of octreotide acetate and the Whipple procedure, the serous amylase and lipase levels returned to normal, and the pancreatic panniculitis had almost resolved by 4 weeks later. Conclusion: Pancreatic panniculitis is a rare complication of pancreatic cancer. However, in the presence of a pancreatic mass, as in this case, clinicians should be aware that panniculitis may be the sentinel of pancreatic carcinoma. PMID:27495045

  10. Inactivation of the dual Bmp/Wnt inhibitor Sostdc1 enhances pancreatic islet function

    PubMed Central

    Henley, Kathryn D.; Gooding, Kimberly A.; Economides, Aris N.

    2012-01-01

    Current endeavors in the type 2 diabetes (T2D) field include gaining a better understanding of extracellular signaling pathways that regulate pancreatic islet function. Recent data suggest that both Bmp and Wnt pathways are operative in pancreatic islets and play a positive role in insulin secretion and glucose homeostasis. Our laboratory found the dual Bmp and Wnt antagonist Sostdc1 to be upregulated in a mouse model of islet dysmorphogenesis and nonimmune-mediated lean diabetes. Because Bmp signaling has been proposed to enhance β-cell function, we evaluated the role of Sostdc1 in adult islet function using animals in which Sostdc1 was globally deleted. While Sostdc1-null animals exhibited no pancreas development phenotype, a subset of mutants exhibited enhanced insulin secretion and improved glucose homeostasis compared with control animals after 12-wk exposure to high-fat diet. Loss of Sostdc1 in the setting of metabolic stress results in altered expression of Bmp-responsive genes in islets but did not affect expression of Wnt target genes, suggesting that Sostdc1 primarily regulates the Bmp pathway in the murine pancreas. Furthermore, our data indicate that removal of Sostdc1 enhances the downregulation of the closely related Bmp inhibitors Ctgf and Gremlin in islets after 8-wk exposure to high-fat diet. These data imply that Sostdc1 regulates expression of these inhibitors and provide a means by which Sostdc1-null animals show enhanced insulin secretion and glucose homeostasis. Our studies provide insights into Bmp pathway regulation in the endocrine pancreas and reveal new avenues for improving β-cell function under metabolic stress. PMID:22829579

  11. Cancer stem cell marker phenotypes are reversible and functionally homogeneous in a preclinical model of pancreatic cancer.

    PubMed

    Dosch, Joseph S; Ziemke, Elizabeth K; Shettigar, Amrith; Rehemtulla, Alnawaz; Sebolt-Leopold, Judith S

    2015-11-01

    Survival rates associated with pancreatic cancer remain dismal despite advancements in detection and experimental treatment strategies. Genetically engineered mouse models of pancreatic tumorigenesis have gained considerable attention based on their ability to recapitulate key clinical features of human disease including chemotherapeutic resistance and fibrosis. However, it is unclear if transgenic systems exemplified by the Kras(G12D)/Trp53(R172H)/Pdx-1-Cre (KPC) mouse model recapitulate the functional heterogeneity of human pancreatic tumors harboring distinct cells with tumorigenic properties. To facilitate tracking of heterogeneous tumor cell populations, we incorporated a luciferase-based tag into the genetic background of the KPC mouse model. We isolated pancreatic cancer cells from multiple independent tumor lines and found that roughly 1 out of 87 cells exhibited tumorigenic capability. Notably, this frequency is significantly higher than reported for human pancreatic adenocarcinomas. Cancer stem cell (CSC) markers, including CD133, CD24, Sca-1, and functional Aldefluor activity, were unable to discriminate tumorigenic from nontumorigenic cells in syngeneic transplants. Furthermore, three-dimensional spheroid cultures originating from KPC tumors did not enrich for cells with stem-like characteristics and were not significantly more tumorigenic than cells cultured as monolayers. Additionally, we did not observe significant differences in response to gemcitabine or salinomycin in several isolated subpopulations. Taken together, these studies show that the hierarchical organization of CSCs in human disease is not recapitulated in a commonly used mouse model of pancreatic cancer and therefore provide a new view of the phenotypic and functional heterogeneity of tumor cells. PMID:26359451

  12. Pancreatic fat and β-cell function in overweight/obese children with nonalcoholic fatty liver disease

    PubMed Central

    Pacifico, Lucia; Di Martino, Michele; Anania, Caterina; Andreoli, Gian Marco; Bezzi, Mario; Catalano, Carlo; Chiesa, Claudio

    2015-01-01

    AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease (NAFLD). METHODS: We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction (HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue (VAT), pancreatic fat fraction (PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance (HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index (WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either: (1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/dL to < 126 mg/dL; (2) impaired glucose tolerance, defined as a 2 h glucose concentration between ≥ 140 mg/dL and < 200 mg/dL; or (3) hemoglobin A1c value of ≥ 5.7% to < 6.5%. RESULTS: PFF was significantly higher in NAFLD patients compared with subjects without liver involvement. PFF was significantly associated with HFF and VAT, as well as fasting insulin, C peptide, HOMA-IR, and WBISI. The association between PFF and HFF was no longer significant after adjusting for age, gender, Tanner stage, body mass index (BMI)-SD score, and VAT. In multiple regression analysis with WBISI or HOMA-IR as the dependent variables, against the covariates age, gender, Tanner stage, BMI-SD score, VAT, PFF, and HFF, the only variable significantly associated with WBISI (standardized coefficient B, -0.398; P = 0.001) as well as HOMA-IR (0.353; P = 0.003) was HFF. Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained

  13. Pancreatic cancer

    PubMed Central

    Güngör, C; Hofmann, B T; Wolters-Eisfeld, G; Bockhorn, M

    2014-01-01

    In recent years, it has become clear that the current standard therapeutic options for pancreatic cancer are not adequate and still do not meet the criteria to cure patients suffering from this lethal disease. Although research over the past decade has shown very interesting and promising new therapeutic options for these patients, only minor clinical success was achieved. Therefore, there is still an urgent need for new approaches that deal with early detection and new therapeutic options in pancreatic cancer. To provide optimal care for patients with pancreatic cancer, we need to understand better its complex molecular biology and thus to identify new target molecules that promote the proliferation and resistance to chemotherapy of pancreatic cancer cells. In spite of significant progress in curing cancers with chemotherapy, pancreatic cancer remains one of the most resistant solid tumour cancers and many studies suggest that drug-resistant cancer cells are the most aggressive with the highest relapse and metastatic rates. In this context, activated Notch signalling is strongly linked with chemoresistance and therefore reflects a rational new target to circumvent resistance to chemotherapy in pancreatic cancer. Here, we have focused our discussion on the latest research, current therapy options and recently identified target molecules such as Notch-2 and the heparin-binding growth factor midkine, which exhibit a wide range of cancer-relevant functions and therefore provide attractive new therapeutic target molecules, in terms of pancreatic cancer and other cancers also. Linked Articles This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4 PMID:24024905

  14. Legacy Effect of Foxo1 in Pancreatic Endocrine Progenitors on Adult β-Cell Mass and Function.

    PubMed

    Talchai, Shivatra Chutima; Accili, Domenico

    2015-08-01

    β-Cell dysfunction in diabetes results from abnormalities of insulin production, secretion, and cell number. These abnormalities may partly arise from altered developmental programming of β-cells. Foxo1 is important to maintain adult β-cells, but little is known about its role in pancreatic progenitor cells as determinants of future β-cell function. We addressed this question by generating an allelic series of somatic Foxo1 knockouts at different stages of pancreatic development in mice. Surprisingly, ablation of Foxo1 in pancreatic progenitors resulted in delayed appearance of Neurogenin3(+) progenitors and their persistence into adulthood as a self-replicating pool, causing a fourfold increase of β-cell mass. Similarly, Foxo1 ablation in endocrine progenitors increased their numbers, extended their survival, and expanded β-cell mass. In contrast, ablation of Foxo1 in terminally differentiated β-cells did not increase β-cell mass nor did it affect Neurogenin3 expression. Despite the increased β-cell mass, islets from mice lacking Foxo1 in pancreatic or endocrine progenitors responded poorly to glucose, resulting in glucose intolerance. We conclude that Foxo1 integrates cues that determine developmental timing, pool size, and functional features of endocrine progenitor cells, resulting in a legacy effect on adult β-cell mass and function. Our results illustrate how developmental programming predisposes to β-cell dysfunction in adults and raise questions on the desirability of increasing β-cell mass for therapeutic purposes in type 2 diabetes. PMID:25784544

  15. Pancreatic Islet Survival and Engraftment Is Promoted by Culture on Functionalized Spider Silk Matrices

    PubMed Central

    Johansson, Ulrika; Dekki Shalaly, Nancy; Zaitsev, Sergei V.; Berggren, Per-Olof; Hedhammar, My

    2015-01-01

    Transplantation of pancreatic islets is one approach for treatment of diabetes, however, hampered by the low availability of viable islets. Islet isolation leads to disruption of the environment surrounding the endocrine cells, which contributes to eventual cell death. The reestablishment of this environment is vital, why we herein investigated the possibility of using recombinant spider silk to support islets in vitro after isolation. The spider silk protein 4RepCT was formulated into three different formats; 2D-film, fiber mesh and 3D-foam, in order to provide a matrix that can give the islets physical support in vitro. Moreover, cell-binding motifs from laminin were incorporated into the silk protein in order to create matrices that mimic the natural cell environment. Pancreatic mouse islets were thoroughly analyzed for adherence, necrosis and function after in vitro maintenance on the silk matrices. To investigate their suitability for transplantation, we utilized an eye model which allows in vivo imaging of engraftment. Interestingly, islets that had been maintained on silk foam during in vitro culture showed improved revascularization. This coincided with the observation of preserved islet architecture with endothelial cells present after in vitro culture on silk foam. Selected matrices were further evaluated for long-term preservation of human islets. Matrices with the cell-binding motif RGD improved human islet maintenance (from 36% to 79%) with preserved islets architecture and function for over 3 months in vitro. The islets established cell-matrix contacts and formed vessel-like structures along the silk. Moreover, RGD matrices promoted formation of new, insulin-positive islet-like clusters that were connected to the original islets via endothelial cells. On silk matrices with islets from younger donors (<35 year), the amount of newly formed islet-like clusters found after 1 month in culture were almost double compared to the initial number of islets

  16. Evolutionary and functional novelty of pancreatic ribonuclease: a study of Musteloidea (order Carnivora).

    PubMed

    Liu, Jiang; Wang, Xiao-ping; Cho, Soochin; Lim, Burton K; Irwin, David M; Ryder, Oliver A; Zhang, Ya-ping; Yu, Li

    2014-01-01

    Pancreatic ribonuclease (RNASE1) is a digestive enzyme that has been one of the key models in studies of evolutionary innovation and functional diversification. It has been believed that the RNASE1 gene duplications are correlated with the plant-feeding adaptation of foregut-fermenting herbivores. Here, we characterized RNASE1 genes from Caniformia, which has a simple digestive system and lacks microbial digestion typical of herbivores, in an unprecedented scope based on both gene sequence and tissue expression analyses. Remarkably, the results yielded new hypotheses regarding the evolution and the function of Caniformia RNASE1 genes. Four independent gene duplication events in the families of superfamily Musteloidea, including Procyonidae, Ailuridae, Mephitidae and Mustelidae, were recovered, rejecting previous Mustelidae-specific duplication hypothesis, but supporting Musteloidea duplication hypothesis. Moreover, our analyses revealed pronounced differences among the RNASE1 gene copies regarding their selection pressures, pI values and tissue expression patterns, suggesting the differences in their physiological functions. Notably, the expression analyses detected the transcription of a RNASE1 pseudogene in several tissues, raising the possibility that pseudogenes are also a potential source during the RNase functional diversification. In sum, the present work demonstrated a far more complex and intriguing evolutionary pattern and functional diversity of mammalian ribonuclease than previously thought. PMID:24861105

  17. Effects of ageing and senescence on pancreatic β-cell function.

    PubMed

    Helman, A; Avrahami, D; Klochendler, A; Glaser, B; Kaestner, K H; Ben-Porath, I; Dor, Y

    2016-09-01

    Ageing is generally associated with deterioration of organ function and regenerative potential. In the case of pancreatic β-cells, an age-related decline in proliferative potential is well documented, and was proposed to contribute to the increased prevalence of type 2 diabetes in the elderly. The effects of ageing on β-cell function, namely glucose-stimulated insulin secretion (GSIS), have not been studied as extensively. Recent work revealed that, surprisingly, β-cells of mature mice and humans secrete more insulin than young β-cells in response to high glucose concentrations, potentially serving to counteract age-related peripheral insulin resistance. This functional change appears to be orchestrated by p16(Ink4A) -driven cellular senescence and downstream remodelling of chromatin structure and DNA methylation, enhancing the expression of genes controlling β-cell function. We propose that activation of the cellular senescence program drives life-long functional maturation of β-cells, due to β-cell hypertrophy, enhanced glucose uptake and more efficient mitochondrial metabolism, in parallel to locking these cells in a non-replicative state. We speculate that the beneficial aspects of this process can be harnessed to enhance GSIS. Other age-related mechanisms, which are currently poorly understood, act to increase basal insulin secretion levels also in low glucose conditions. This leads to an overall reduction in the amplitude of insulin secretion between low and high glucose at old age, which may contribute to a deterioration in metabolic control. PMID:27615132

  18. GALACSI integration and functional tests

    NASA Astrophysics Data System (ADS)

    La Penna, P.; Ströbele, S.; Aller Carpentier, E.; Argomedo, J.; Arsenault, R.; Conzelmann, R. D.; Delabre, B.; Donaldson, R.; Duchateau, M.; Fedrigo, E.; Gago, F.; Hubin, N.; Quentin, J.; Jolley, P.; Kiekebusch, M.; Kirchbauer, J. P.; Klein, B.; Kolb, J.; Kuntschner, H.; Le Louarn, M.; Lizon, J. L.; Madec, P.-.; Manescau, A.; Mehrgan, L.; Sedghi, B.; Suarez Valles, M.; Soenke, C.; Tordo, S.; Vernet, J.; Zampieri, S.

    2014-07-01

    GALACSI is the Adaptive Optics (AO) modules of the ESO Adaptive Optics Facility (AOF) that will correct the wavefront delivered to the MUSE Integral Field Spectrograph. It will sense with four 40×40 subapertures Shack-Hartmann wavefront sensors the AOF 4 Laser Guide Stars (LGS), acting on the 1170 voice-coils actuators of the Deformable Secondary Mirror (DSM). GALACSI has two operating modes: in Wide Field Mode (WFM), with the four LGS at 64" off axis, the collected energy in a 0.2"×0.2" pixel will be enhanced by a factor 2 at 750 nm over a Field of View (FoV) of 1'×1' using the Ground Layer AO (GLAO) technique. The other mode, the Narrow Field Mode (NFM), provides an enhanced wavefront correction (Strehl Ratio (SR) of 5% (goal 10%) at 650 nm) but in a smaller FoV (7.5"×7.5"), using Laser Tomography AO (LTAO), with the 4 LGS located closer, at 10" off axis. Before being shipped to Paranal, GALACSI will be first integrated and fully tested in stand-alone, and then moved to a dedicated AOF facility to be tested with the DSM in Europe. At present the module is fully assembled, its main functionalities have been implemented and verified, and AO system tests with the DSM are starting. We present here the main system features and the results of the internal functional tests of GALACSI.

  19. [Treatment Strategy for Non-Functional Pancreatic Neuroendocrine Tumors (P-NETs) at Kurume University Hospital].

    PubMed

    Kawashima, Yusuke; Ishikawa, Hiroto; Hisaka, Toru; Okuda, Kouji; Akagi, Yoshito

    2016-01-01

    Pancreatic neuroendocrine tumors (P-NETs) are relatively rare. Approximately 50-90% of non-functioning P-NETs are malignant, and the only curative treatment is surgical resection. Liver and lymph node metastases often occur. In Japan, the mTOR inhibitor everolimus is now covered by the national health insurance for treatment of P-NETs, including advanced and unresectable tumors. We present a case of P-NETs with liver metastases seen at our hospital and discuss our treatment strategy for this disease. Patients with tumors≤1 cm receive follow-up observation. For G1 and G2 (other than G3) tumors, if their size is >1 cm when first discovered, resection of the primary lesion along with lymph node dissection (as for pancreatic cancer) is performed. In G1 and G2 tumors with synchronous distant metastases, the primary lesion is first resected, and depending on the pathological findings, chemotherapy (LAR plus everolimus) may be administered. After 4 courses of chemotherapy, the response is assessed, and if further resection is possible, resection is performed. When there are synchronous liver metastases, if partial resection and local treatment (such as RFA) are possible, the primary lesion and synchronous lesions are resected. If a major hepatic resection procedure such as a segmentectomy or lobectomy is possible, the primary lesion is resected, followed by chemotherapy. After 4 courses of chemotherapy, the response is assessed, and if further resection is possible, hepatic resection is performed. G3 tumors are usually highly malignant, advanced, and often associated with metastases at the time of diagnosis. Chemotherapy may be an option for treating patients with G3 tumors. PMID:26809536

  20. Effects of early enteral nutrition on immune function of severe acute pancreatitis patients

    PubMed Central

    Sun, Jia-Kui; Mu, Xin-Wei; Li, Wei-Qin; Tong, Zhi-Hui; Li, Jing; Zheng, Shu-Yun

    2013-01-01

    AIM: To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP). METHODS: Patients were randomly allocated to receive EEN or delayed enteral nutrition (DEN). Enteral nutrition was started within 48 h after admission in EEN group, whereas from the 8th day in DEN group. All the immunologic parameters and C-reactive protein (CRP) levels were collected on days 1, 3, 7 and 14 after admission. The clinical outcome variables were also recorded. RESULTS: Sixty SAP patients were enrolled to this study. The CD4+ T-lymphocyte percentage, CD4+/CD8+ ratio, and the CRP levels in EEN group became significantly lower than in DEN group from the 7th day after admission. In contrast, the immunoglobulin G (IgG) levels and human leukocyte antigen-DR expression in EEN group became significantly higher than in DEN group from the 7th day after admission. No difference of CD8+ T-lymphocyte percentage, IgM and IgA levels was found between the two groups. The incidences of multiple organ dysfunction syndrome, systemic inflammatory response syndrome, and pancreatic infection as well as the duration of intensive care unit stay were significantly lower in EEN group than in DEN group. However, there was no difference of hospital mortality between the two groups. CONCLUSION: EEN moderates the excessive immune response during the early stage of SAP without leading to subsequent immunosuppression. EEN can improve the clinical outcome, but not decrease the hospital mortality of SAP patients. PMID:23431120

  1. MUC1-specific CTLs are non-functional within a pancreatic tumor microenvironment.

    PubMed

    Mukherjee, P; Ginardi, A R; Madsen, C S; Tinder, T L; Jacobs, F; Parker, J; Agrawal, B; Longenecker, B M; Gendler, S J

    2001-01-01

    Pancreatic cancer is a highly aggressive, treatment refractory disease and is the fourth leading cause of death in the United States. In humans, 90% of pancreatic adenocarcinomas over-express altered forms of a tumor-associated antigen, MUC1 (an epithelial mucin glycoprotein), which is a target for immunotherapy. Using a clinically relevant mouse model of pancreas cancer that demonstrates peripheral and central tolerance to human MUC1 and develops spontaneous tumors of the pancreas, we have previously reported the presence of functionally active, low affinity, MUC1-specific precursor cytotoxic T cells (pCTLs). Hypothesis for this study is that MUC1-based immunization may enhance the low level MUC1-specific immunity that may lead to an effective anti-tumor response. Data demonstrate that MUC1 peptide-based immunization elicits mature MUC1-specific CTLs in the peripheral lymphoid organs. The mature CTLs secrete IFN-gamma and are cytolytic against MUC1-expressing tumor cells in vitro. However, active CTLs that infiltrate the pancreas tumor microenvironment become cytolytically anergic and are tolerized to MUC1 antigen, allowing the tumor to grow. We demonstrate that the CTL tolerance could be reversed at least in vitro with the use of anti-CD40 co-stimulation. The pancreas tumor cells secrete immunosuppressive cytokines, including IL-10 and TGF-beta that are partly responsible for the down-regulation of CTL activity. In addition, they down-regulate their MHC class I molecules to avoid immune recognition. CD4+ CD25+ T regulatory cells, which secrete IL-10, were also found in the tumor environment. Together these data indicate the use of several immune evasion mechanisms by tumor cells to evade CTL killing. Thus altering the tumor microenvironment to make it more conducive to CTL killing may be key in developing a successful anti-cancer immunotherapy. PMID:12820727

  2. Abnormality on Liver Function Test

    PubMed Central

    2013-01-01

    Children with abnormal liver function can often be seen in outpatient clinics or inpatients wards. Most of them have respiratory disease, or gastroenteritis by virus infection, accompanying fever. Occasionally, hepatitis by the viruses causing systemic infection may occur, and screening tests are required. In patients with jaundice, the tests for differential diagnosis and appropriate treatment are important. In the case of a child with hepatitis B virus infection vertically from a hepatitis B surface antigen positive mother, the importance of the recognition of immune clearance can't be overstressed, for the decision of time to begin treatment. Early diagnosis changes the fate of a child with Wilson disease. So, screening test for the disease should not be omitted. Non-alcoholic fatty liver disease, which is mainly discovered in obese children, is a new strong candidate triggering abnormal liver function. Muscular dystrophy is a representative disease mimicking liver dysfunction. Although muscular dystrophy is a progressive disorder, and early diagnosis can't change the fate of patients, it will be better to avoid parent's blame for delayed diagnosis. PMID:24511518

  3. Butyrate alleviates metabolic impairments and protects pancreatic β cell function in pregnant mice with obesity

    PubMed Central

    Li, Hua-Ping; Chen, Xuan; Li, Ming-Qing

    2013-01-01

    The relative or absolute deficiency of pancreatic β-cell mass function underlies the pathogenesis of diabetes. It is necessary to alleviate the metabolic stress and reduce the demand for insulin to decrease the effects of mutations affecting β-cell expansion. Butyrate is a natural nutrient existed in food and can also be produced physiologically through the intestinal fermentation of fiber. Pregnancy and obesity model would be helpful for understanding how β-cell adapt to insulin resistance and how butyrate alleviate the metabolic impairment and protect pancreatic β cell function in pregnant mice with obesity. C57BL/6J female mice were divided into three groups and fed with high fat food (HF group, 40% energy from fat), high fat with sodium butyrate food (HSF group, 95% HF with 5% butyrate), or control food (CF group, 14% energy from fat), respectively. The feeding would last for 14 weeks before mating and throughout the gestation period. A subset of dams were sacrificed at gestational day (GD) 14.5 to evaluate the changes of metabolism and β-cell function, mass, proliferation and apoptosis, inflammatory reaction of islet from different diet. Pancreases were double immuno-labeled to assess the islet morphology, insulin expression, expression of proliferation gene PCNA and anti-apoptosis gene bcl-2. Moreover, we detected the expression of NF-κB, phosphorylated NF-κB (pNF-κB) to evaluate the islet inflammatory response with immunohistochemistry. Mice fed with HSF showed obviously changes including the decreased values of weight gain, glucose, insulin, triglyceride and total cholesterol level of blood compared with high fat diet group, and the reduced circulating maternal pro-inflammation factors at GD14.5. Mice fed with HF displayed β-cell hyperplasia with a greater β-cell size and β-cell area in pancreas. Furthermore, the higher ratio of apoptosis and inflammatory response were found in HF group compared with HSF and CF group, while the proliferation

  4. One-step purification of functional human and rat pancreatic alpha cells.

    PubMed

    Köhler, Martin; Daré, Elisabetta; Ali, Muhammed Yusuf; Rajasekaran, Subu Surendran; Moede, Tilo; Leibiger, Barbara; Leibiger, Ingo B; Tibell, Annika; Juntti-Berggren, Lisa; Berggren, Per-Olof

    2012-02-01

    Pancreatic alpha cells contribute to glucose homeostasis by the regulated secretion of glucagon, which increases glycogenolysis and hepatic gluconeogenesis in response to hypoglycemia. Alterations of glucagon secretion are observed in diabetic patients and exacerbate the disease. The restricted availability of purified primary alpha cells has limited our understanding of their function in health and disease. This study was designed to establish convenient protocols for the purification of viable alpha cells from rat and human pancreatic islets by FACS, using intrinsic cellular properties. Islets were isolated from the pancreata of Wistar rats or deceased human organ donors. Dispersed islet cells were separated by FACS based on light scatter and autofluorescence. Purity of sorted cells was evaluated by immunocytochemistry using hormone specific antibodies. Relative hormone expression was further determined by quantitative RT-PCR. Viability was determined by Annexin V and propidium iodide staining and function was assessed by monitoring cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) using Fura-2/AM. We developed species-specific FACS gating strategies that resulted in populations consisting mainly of alpha cells (96.6 ± 1.4%, n = 3 for rat; 95.4 ± 1.7%, n = 4 for human, mean ± SEM). These cell fractions showed ~5-fold and ~4-fold enrichment (rat and human, respectively) of glucagon mRNA expression compared to total ungated islet cells. Most of the sorted cells were viable and functional, as they responded with an increase in [Ca(2+)](i) upon stimulation with L-arginine (10 mM). The majority of the sorted human alpha cells responded also to stimulation with kainate (100 μM), whereas this response was infrequent in rat alpha cells. Using the same sample preparation, but a different gating strategy, we were also able to sort rat and human populations enriched in beta cells. In conclusion, we have simplified and optimized a method for the purification of rat

  5. Functional Proteomics Screen Enables Enrichment of Distinct Cell Types from Human Pancreatic Islets

    PubMed Central

    Sharivkin, Revital; Walker, Michael D.; Soen, Yoav

    2015-01-01

    The current world-wide epidemic of diabetes has prompted attempts to generate new sources of insulin-producing cells for cell replacement therapy. An inherent challenge in many of these strategies is the lack of cell-surface markers permitting isolation and characterization of specific cell types from differentiating stem cell populations. Here we introduce an iterative proteomics procedure allowing tag-free isolation of cell types based on their function. Our method detects and associates specific cell-surface markers with particular cell functionality by coupling cell capture on antibody arrays with immunofluorescent labeling. Using this approach in an iterative manner, we discovered marker combinations capable of enriching for discrete pancreatic cell subtypes from human islets of Langerhans: insulin-producing beta cells (CD9high/CD56+), glucagon-producing alpha cells (CD9- /CD56+) and trypsin-producing acinar cells (CD9- /CD56-). This strategy may assist future beta cell research and the development of diagnostic tools for diabetes. It can also be applied more generally for function-based purification of desired cell types from other limited and heterogeneous biological samples. PMID:25706282

  6. Secreted factors from dental pulp stem cells improve glucose intolerance in streptozotocin-induced diabetic mice by increasing pancreatic β-cell function

    PubMed Central

    Izumoto-Akita, Takako; Tsunekawa, Shin; Yamamoto, Akihito; Uenishi, Eita; Ishikawa, Kota; Ogata, Hidetada; Iida, Atsushi; Ikeniwa, Makoto; Hosokawa, Kaori; Niwa, Yasuhiro; Maekawa, Ryuya; Yamauchi, Yuichiro; Seino, Yusuke; Hamada, Yoji; Hibi, Hideharu; Arima, Hiroshi; Ueda, Minoru; Oiso, Yutaka

    2015-01-01

    Objective Many studies have reported that stem cell transplantation promotes propagation and protection of pancreatic β-cells in streptozotocin (STZ)-induced diabetic mice without the differentiation of transplanted cells into pancreatic β-cells, suggesting that the improvement is due to a paracrine effect of the transplanted cells. We investigated the effects of factors secreted by dental pulp stem cells from human exfoliated deciduous teeth (SHED) on β-cell function and survival. Research design and methods Conditioned medium from SHED (SHED-CM) was collected 48 h after culturing in serum-free Dulbecco's modified Eagle's medium (DMEM). The insulin levels in SHED-CM and serum-free conditioned media from human bone marrow-derived mesenchymal stem cells (BM-CM) were undetectable. STZ-induced diabetic male C57B/6J mice were injected with DMEM as a control, SHED-CM, exendin-4 (Ex-4), or BM-CM for 14 days. Mouse pancreatic β-cell line MIN6 cells were incubated with different concentrations of STZ with SHED-CM, DMEM, Ex-4, or BM-CM for 6 h. Results Administration of 1 mL of SHED-CM twice a day improved glucose intolerance in STZ-induced diabetic mice and the effect continued for 20 days after the end of treatment. SHED-CM treatment increased pancreatic insulin content and β-cell mass through proliferation and an intraperitoneal glucose tolerance test revealed enhanced insulin secretion. Incubation of MIN6 cells (a mouse pancreatic β-cell line) with SHED-CM enhanced insulin secretion in a glucose concentration-dependent manner and reduced STZ-induced cell death, indicating that the amelioration of hyperglycemia was caused by the direct effects of SHED-CM on β-cell function and survival. These effects were more pronounced than with the use of Ex-4, a conventional incretin-based drug, and BM-CM, which is a medium derived from other stem cells. Conclusions These findings suggest that SHED-CM provides direct protection and encourages the propagation of

  7. [Exercise test and respiratory muscle function test].

    PubMed

    Akashiba, Tsuneto

    2011-10-01

    Dyspnea on exertion is a chief complaint of patients with COPD, and it has a major effect on the quality of their lives. Dyspnea is, by definition, subjective, but objective approaches are needed for a comprehensive understanding of these patients' conditions. Thus, measuring changes in cardiopulmonary variables during exercise can be very helpful when evaluating patients with COPD. The main purpose of exercise testing is to evaluate exercise tolerance and to identify the factors limiting exercise. Although incremental exercise testing is ideal for these purposes, simple walking tests such as 6-minute walking test, are also useful. PMID:22073578

  8. Threshold-Dependent Cooperativity of Pdx1 and Oc1 in Pancreatic Progenitors Establishes Competency for Endocrine Differentiation and β-Cell Function.

    PubMed

    Henley, Kathryn D; Stanescu, Diana E; Kropp, Peter A; Wright, Christopher V E; Won, Kyoung-Jae; Stoffers, Doris A; Gannon, Maureen

    2016-06-21

    Pdx1 and Oc1 are co-expressed in multipotent pancreatic progenitors and regulate the pro-endocrine gene Neurog3. Their expression diverges in later organogenesis, with Oc1 absent from hormone+ cells and Pdx1 maintained in mature β cells. In a classical genetic test for cooperative functional interactions, we derived mice with combined Pdx1 and Oc1 heterozygosity. Endocrine development in double-heterozygous pancreata was normal at embryonic day (E)13.5, but defects in specification and differentiation were apparent at E15.5, the height of the second wave of differentiation. Pancreata from double heterozygotes showed alterations in the expression of genes crucial for β-cell development and function, decreased numbers and altered allocation of Neurog3-expressing endocrine progenitors, and defective endocrine differentiation. Defects in islet gene expression and β-cell function persisted in double heterozygous neonates. These results suggest that Oc1 and Pdx1 cooperate prior to their divergence, in pancreatic progenitors, to allow for proper differentiation and functional maturation of β cells. PMID:27292642

  9. Threshold-dependent cooperativity of Pdx1 and Oc1 in pancreatic progenitors establishes competency for endocrine differentiation and β-cell function

    PubMed Central

    Wright, Christopher V.E.; Won, Kyoung-Jae

    2016-01-01

    Summary Pdx1 and Oc1 are co-expressed in multipotent pancreatic progenitors and regulate the pro-endocrine gene Neurog3. Their expression diverges in later organogenesis, with Oc1 absent from hormone+ cells and Pdx1 maintained in mature β cells. In a classical genetic test for cooperative functional interactions, we derived mice with combined Pdx1 and Oc1 heterozygosity. Endocrine development in double-heterozygous pancreata was normal at embryonic day (e)13.5, but defects in specification and differentiation were apparent at e15.5, the height of the second wave of differentiation. Pancreata from double heterozygotes showed alterations in the expression of genes crucial for β-cell development and function, decreased numbers and altered allocation of Neurog3-expressing endocrine progenitors, and defective endocrine differentiation. Defects in islet gene expression and β-cell function persisted in double heterozygous neonates. These results suggest that Oc1 and Pdx1 cooperate prior to their divergence, in pancreatic progenitors, to allow for proper differentiation and functional maturation of β cells. PMID:27292642

  10. A Multistep High-Content Screening Approach to Identify Novel Functionally Relevant Target Genes in Pancreatic Cancer

    PubMed Central

    Buchholz, Malte; Honstein, Tatjana; Kirchhoff, Sandra; Kreider, Ramona; Schmidt, Harald; Sipos, Bence; Gress, Thomas M.

    2015-01-01

    In order to foster the systematic identification of novel genes with important functional roles in pancreatic cancer, we have devised a multi-stage screening strategy to provide a rational basis for the selection of highly relevant novel candidate genes based on the results of functional high-content analyses. The workflow comprised three consecutive stages: 1) serial gene expression profiling analyses of primary human pancreatic tissues as well as a number of in vivo and in vitro models of tumor-relevant characteristics in order to identify genes with conspicuous expression patterns; 2) use of ‘reverse transfection array’ technology for large-scale parallelized functional analyses of potential candidate genes in cell-based assays; and 3) selection of individual candidate genes for further in-depth examination of their cellular roles. A total of 14 genes, among them 8 from “druggable” gene families, were classified as high priority candidates for individual functional characterization. As an example to demonstrate the validity of the approach, comprehensive functional data on candidate gene ADRBK1/GRK2, which has previously not been implicated in pancreatic cancer, is presented. PMID:25849100

  11. Acute Pancreatitis Induced by Azathioprine and 6-mercaptopurine Proven by Single and Low Dose Challenge Testing in a Child with Crohn Disease.

    PubMed

    Yi, Geum-Chae-Won; Yoon, Ka-Hyun; Hwang, Jin-Bok

    2012-12-01

    We report here a case of drug-induced acute pancreatitis proved by elimination and single, low dose challenge test in a child with Crohn disease. A 14-year-old boy with moderate/severe Crohn disease was admitted due to high fever and severe epigastric pain during administration of mesalazine and azathioprine. Blood test and abdominal ultrasonography revealed acute pancreatitis. After discontinuance of the medication and supportive care, the symptoms and laboratory findings improved. A single, low dose challenge test was done to confirm the relationship of the adverse drug reaction and acute pancreatitis, and to discriminate the responsible drug. Azathioprine and 6-mercaptopurine showed positive responses, and mesalazine showed a negative response. We introduce the method of single, low dose challenge test and its interpretation for drug-induced pancreatitis. PMID:24010098

  12. Obestatin Accelerates the Recovery in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

    PubMed Central

    Bukowczan, Jakub; Warzecha, Zygmunt; Ceranowicz, Piotr; Kuśnierz-Cabala, Beata; Tomaszewska, Romana

    2015-01-01

    Objective Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis, and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration following the onset of experimental acute pancreatitis. Aim The aim of this study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. Moreover, we tested the influence of ischemia/reperfusion-induced acute pancreatitis and administration of obestatin on daily food intake and pancreatic exocrine secretion. Methods Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8nmol/kg/dose) was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. Secretory studies were performed on the third day after sham-operation or induction of acute pancreatitis in conscious rats equipped with chronic pancreatic fistula. Results Treatment with obestatin ameliorated morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland, and led to earlier pancreatic regeneration. Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1β level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow. Induction of acute pancreatitis by pancreatic ischemia followed by reperfusion significantly decreased daily food

  13. miR-184 Regulates Pancreatic β-Cell Function According to Glucose Metabolism.

    PubMed

    Tattikota, Sudhir G; Rathjen, Thomas; Hausser, Jean; Khedkar, Aditya; Kabra, Uma D; Pandey, Varun; Sury, Matthias; Wessels, Hans-Hermann; Mollet, Inês G; Eliasson, Lena; Selbach, Matthias; Zinzen, Robert P; Zavolan, Mihaela; Kadener, Sebastian; Tschöp, Matthias H; Jastroch, Martin; Friedländer, Marc R; Poy, Matthew N

    2015-08-14

    In response to fasting or hyperglycemia, the pancreatic β-cell alters its output of secreted insulin; however, the pathways governing this adaptive response are not entirely established. Although the precise role of microRNAs (miRNAs) is also unclear, a recurring theme emphasizes their function in cellular stress responses. We recently showed that miR-184, an abundant miRNA in the β-cell, regulates compensatory proliferation and secretion during insulin resistance. Consistent with previous studies showing miR-184 suppresses insulin release, expression of this miRNA was increased in islets after fasting, demonstrating an active role in the β-cell as glucose levels lower and the insulin demand ceases. Additionally, miR-184 was negatively regulated upon the administration of a sucrose-rich diet in Drosophila, demonstrating strong conservation of this pathway through evolution. Furthermore, miR-184 and its target Argonaute2 remained inversely correlated as concentrations of extracellular glucose increased, underlining a functional relationship between this miRNA and its targets. Lastly, restoration of Argonaute2 in the presence of miR-184 rescued suppression of miR-375-targeted genes, suggesting these genes act in a coordinated manner during changes in the metabolic context. Together, these results highlight the adaptive role of miR-184 according to glucose metabolism and suggest the regulatory role of this miRNA in energy homeostasis is highly conserved. PMID:26152724

  14. Functional Task Test: Data Review

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita

    2014-01-01

    After space flight there are changes in multiple physiological systems including: Cardiovascular function; Sensorimotor function; and Muscle function. How do changes in these physiological system impact astronaut functional performance?

  15. Improvement in The Function of Isolated Rat Pancreatic Islets through Reduction of Oxidative Stress Using Traditional Iranian Medicine

    PubMed Central

    Mahroui, Neda; Mirzaei, Sanaz; Siahpoosh, Zahra; D.4, Pharm.; Nili-Ahmadabadi, Amir; Mohammadirad, Azadeh; Baeeri, Maryam; Hajiaghaie, Reza; Abdollahi, Mohammad

    2014-01-01

    Objective Pancreatic islets have fewer antioxidant enzymes than other tissues and thus are vulnerable to oxidative stress. In the present study, the effects of nine specifically selected Iranian medical plants on the mitochondria function and survival of isolated rat islets were examined. Materials and Methods In this experimental study, following laparotomy, pancreases of rats were removed and the islets isolated and incubated in vitro for 24 hours. Logarithmic doses of plant materials were added to the islets and incubated for an additional 24 hours after which the viability of the cells and production of reactive oxygen species (ROS) were measured. Levels of insulin production in relation to static and stimulated glucose concen- trations were also determined. Results The tested compounds markedly increased survival of the islet cells, their mi- tochondrial activity, and insulin levels at the same time as reducing production of ROS. Greatest effects were observed in the following order: Peganum harmala, Glycyrrhiza glabra, Satureja hortensis, Rosmarinus officinalis, Teucrium scordium, Aloe vera, Zingiber officinale, Silybum marianum, and Hypericum perforatum at doses of 10, 103, 104, 10, 102, 102, 10-1, 10 and 103μgmL-1, respectively. Conclusion Based on these results, we suggest that pretreatment with these select- ed Iranian medical plants can improve the outcomes of pancreas transplants and grafts through the control of oxidative stress damage. PMID:24567945

  16. Surgical Approaches to Chronic Pancreatitis

    PubMed Central

    Hartmann, Daniel; Friess, Helmut

    2015-01-01

    Chronic pancreatitis is a progressive inflammatory disease resulting in permanent structural damage of the pancreas. It is mainly characterized by recurring epigastric pain and pancreatic insufficiency. In addition, progression of the disease might lead to additional complications, such as pseudocyst formation or development of pancreatic cancer. The medical and surgical treatment of chronic pancreatitis has changed significantly in the past decades. With regard to surgical management, pancreatic head resection has been shown to be a mainstay in the treatment of severe chronic pancreatitis because the pancreatic head mass is known to trigger the chronic inflammatory process. Over the years, organ-preserving procedures, such as the duodenum-preserving pancreatic head resection and the pylorus-preserving Whipple, have become the surgical standard and have led to major improvements in pain relief, preservation of pancreatic function, and quality of life of patients. PMID:26681935

  17. 14 CFR 35.40 - Functional test.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Functional test. 35.40 Section 35.40... STANDARDS: PROPELLERS Tests and Inspections § 35.40 Functional test. The variable-pitch propeller system must be subjected to the applicable functional tests of this section. The same propeller system used...

  18. 14 CFR 35.40 - Functional test.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Functional test. 35.40 Section 35.40... STANDARDS: PROPELLERS Tests and Inspections § 35.40 Functional test. The variable-pitch propeller system must be subjected to the applicable functional tests of this section. The same propeller system used...

  19. 14 CFR 35.40 - Functional test.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Functional test. 35.40 Section 35.40... STANDARDS: PROPELLERS Tests and Inspections § 35.40 Functional test. The variable-pitch propeller system must be subjected to the applicable functional tests of this section. The same propeller system used...

  20. Pancreatic acellular matrix supports islet survival and function in a synthetic tubular device: in vitro and in vivo studies.

    PubMed

    De Carlo, E; Baiguera, S; Conconi, M T; Vigolo, S; Grandi, C; Lora, S; Martini, C; Maffei, P; Tamagno, G; Vettor, R; Sicolo, N; Parnigotto, P P

    2010-02-01

    Increasing pancreatic islet survival and function is a starting point for obtaining a valuable bioartificial pancreas for the treatment of type 1 diabetes. In this context, decellularized matrices, obtained after the removal of tissue cellular part, are known to support in vitro adhesion, growth, and function of several cell types. We demonstrate that a homologous acellular pancreatic matrix is a suitable scaffold for rat islet cultures maintaining their long-term viability and function. Islets adhered to the pancreatic matrix showed a constant glucose-induced insulin release during long-term in vitro incubation, while islets cultured without a matrix or on the liver matrix showed a progressive reduction. In order to obtain implantable devices, acellular matrix/islet cultures were entrapped into poly(vinyl alcohol) (PVA)/ poly(ethylene glycol) (PEG) tubes obtained by the freezing/thawing procedure. Under this condition, an in vitro constant insulin release was detected. The devices were then implanted into diabetic rats where reduced insulin requirement was noted suggesting insulin secretory activity of islets contained in the device. Indeed, immunofluorescence confirmed the presence of insulin- and glucagon-producing cells into the explanted devices. These data show that PVA/PEG semi-permeable membrane can obtain devices that restore, at least in part, insulin secretion. PMID:20043127

  1. Sonic hedgehog derived from human pancreatic cancer cells augments angiogenic function of endothelial progenitor cells.

    PubMed

    Yamazaki, Madoka; Nakamura, Kazumasa; Mizukami, Yusuke; Ii, Masaaki; Sasajima, Junpei; Sugiyama, Yoshiaki; Nishikawa, Tomoya; Nakano, Yasuhiro; Yanagawa, Nobuyuki; Sato, Kazuya; Maemoto, Atsuo; Tanno, Satoshi; Okumura, Toshikatsu; Karasaki, Hidenori; Kono, Toru; Fujiya, Mikihiro; Ashida, Toshifumi; Chung, Daniel C; Kohgo, Yutaka

    2008-06-01

    Hedgehog signaling is important in the pathogenesis of pancreatic cancer. Several recent observations suggest the involvement of sonic hedgehog (SHH) in postnatal neovascularization. We identified a novel role for SHH in tumor-associated angiogenesis in pancreatic cancer. Immunohistochemical analysis revealed that patched homolog 1 (PTCH1), both a receptor for and transcriptional target of hedgehog signaling, was expressed in a small fraction of endothelial cells within pancreatic cancer, but not in normal pancreatic tissue. When endothelial progenitor cells (EPC) isolated from human peripheral blood were cultured with supernatant from SHH-transfected 293 cells or pancreatic cancer cells, mRNA levels of vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 and angiopoietin-1 were significantly increased, whereas no such induction was observed in human umbilical vein endothelial cell (HUVEC) and human dermal microvascular endothelial cell (HMVEC). HUVEC tube formation was stimulated when cocultured with EPC, and preconditioning EPC with supernatant from KP-1 N pancreatic cancer cells highly expressing SHH significantly enhanced the effect. The effect was partially attenuated by specific inhibition of SHH with cyclopamine or a neutralizing antibody. These findings suggest that tumor-derived SHH can induce angiogenesis, and this is mediated by its effects on EPC specifically. Targeting SHH would be a novel therapeutic approach that can inhibit not only proliferation of cancer cells but also EPC-mediated angiogenesis. PMID:18422746

  2. Quantitative functional MRI in a clinical orthotopic model of pancreatic cancer in immunocompetent Lewis rats

    PubMed Central

    Zhang, Zhuoli; Zheng, Linfeng; Li, Weiguo; Gordon, Andrew C; Huan, Yi; Shangguan, Junjie; Procissi, Daniel; Bentrem, David J; Larson, Andrew C

    2015-01-01

    Objective: To demonstrate feasibility of performing quantitative MRI measurements in an immuno-competent rat model of pancreatic cancer by comparing in vivo anatomic and quantitative imaging measurements to tumor dissemination observations and histologic assays at necropsy. Meterials and methods: Rat ductal pancreatic adenocarcinoma DSL-6A/C1 cell line and Lewis rats were used for these studies. 108 DSL-6A/C1 cells were injected subcutaneously into the right flank of donor rats. Donor tumors reaching 10 mm were excised, and 1 mm3 tumor fragments were implanted within recipient rat pancreas during mini-laparotomy. T1-weighted, T2-weighted, diffusion-weighted, and dynamic contrast-enhanced (DCE) MRI were performed using a Bruker 7.0T ClinScan. After MRI, all animals underwent autopsy. Primary tumor size was measured, and dissemination score was used to assess local invasion and distant metastasis. Primary tumor and all sites of metastases were harvested and fixed for H&E, Masson’s trichrome, and rat anti-CD34 staining. Trichrome slides were scanned and digitized for measurement of fibrotic tissue areas. Anti-CD34 slides were used for microvessel density (MVD) measurements. Results: Primary tumors, local invasion, and distant metastases were confirmed for all rats. No significant differences were found between in vivo MRI measurements (48.7 ± 5.3 mm) and ex vivo caliper measurements (43.6 ± 3.6 mm) of primary tumor sizes (p > .05). Spleen, liver, diaphragm, peritoneum, and abdominal wall metastases were observed on MRI but smaller lung, mediastinum, omen, and mesentery metastases were only observed at necropsy. Contrast uptake observed during DCE measurements was significantly greater in both primary and metastatic tumor tissues compared to skeletal muscle and normal liver tissues. Both primary and metastatic tumors were hyper-intense in T2-weighted images and hypo-intense in T1-weighted images, but no differences were found between quantitative T2 measurements in

  3. The functional performance of microencapsulated human pancreatic islet-derived precursor cells.

    PubMed

    Montanucci, Pia; Pennoni, Ilaria; Pescara, Teresa; Blasi, Paolo; Bistoni, Giovanni; Basta, Giuseppe; Calafiore, Riccardo

    2011-12-01

    We have examined long-term cultured, human islet-derived stem/precursor cells (hIPC). Whole human islets (HI) were obtained by multi-enzymatic digestion of cadaveric donor pancreases, plated on tissue flasks, and allowed to adhere and expand for several in vitro passages, in order to obtain hIPC. We detected specific stem cell markers (Oct-4, Sox-2, Nanog, ABCG2, Klf-4, CD117) in both intact HI and hIPC. Moreover, hIPC while retaining the expression of Glut-2, Pdx-1, CK-19, and ICA-512, started re-expressing Ngn3, thereby indicating acquisition of a specific pancreatic islet beta cell-oriented phenotype identity. The intrinsic plasticity of hIPC was documented by their ability to differentiate into various germ layer-derived cell phenotypes (ie, osteocytic, adipocytic and neural), including endocrine cells associated with insulin secretory capacity. To render hIPC suitable for transplantation we have enveloped them within our highly purified, alginate-based microcapsules. Upon intraperitoneal graft in NOD/SCID mice we have observed that the microcapsules acted as three-dimensional niches favouring post-transplant hIPC differentiation and acquisition of beta cell-like functional competence. PMID:21889203

  4. Microbead-based biomimetic synthetic neighbors enhance survival and function of rat pancreatic β-cells

    NASA Astrophysics Data System (ADS)

    Li, Wei; Lee, Samuel; Ma, Minglin; Kim, Soo Min; Guye, Patrick; Pancoast, James R.; Anderson, Daniel G.; Weiss, Ron; Lee, Richard T.; Hammond, Paula T.

    2013-10-01

    Diabetes is caused by the loss or dysfunction of insulin-secreting β-cells in the pancreas. β-cells reduce their mass and lose insulin-producing ability in vitro, likely due to insufficient cell-cell and cell-extracellular matrix (ECM) interactions as β-cells lose their native microenvironment. Herein, we built an ex-vivo cell microenvironment by culturing primary β-cells in direct contact with `synthetic neighbors', cell-sized soft polymer microbeads that were modified with cell-cell signaling factors as well as components from pancreatic-tissue-specific ECMs. This biomimetic 3D microenvironment was able to promote native cell-cell and cell-ECM interactions. We obtained sustained maintenance of β-cell function in vitro enhanced cell viability from the few days usually observed in 2D culture to periods exceeding three weeks, with enhanced β-cell stability and insulin production. Our approach can be extended to create a general 3D culture platform for other cell types.

  5. Iron Regulation of Pancreatic Beta-Cell Functions and Oxidative Stress.

    PubMed

    Backe, Marie Balslev; Moen, Ingrid Wahl; Ellervik, Christina; Hansen, Jakob Bondo; Mandrup-Poulsen, Thomas

    2016-07-17

    Dietary advice is the cornerstone in first-line treatment of metabolic diseases. Nutritional interventions directed at these clinical conditions mainly aim to (a) improve insulin resistance by reducing energy-dense macronutrient intake to obtain weight loss and (b) reduce fluctuations in insulin secretion through avoidance of rapidly absorbable carbohydrates. However, even in the majority of motivated patients selected for clinical trials, massive efforts using this approach have failed to achieve lasting efficacy. Less attention has been given to the role of micronutrients in metabolic diseases. Here, we review the evidence that highlights (a) the importance of iron in pancreatic beta-cell function and dysfunction in diabetes and (b) the integrative pathophysiological effects of tissue iron levels in the interactions among the beta cell, gut microbiome, hypothalamus, innate and adaptive immune systems, and insulin-sensitive tissues. We propose that clinical trials are warranted to clarify the impact of dietary or pharmacological iron reduction on the development of metabolic disorders. PMID:27146016

  6. Immune Intervention and Preservation of Pancreatic Beta Cell Function in Type 1 Diabetes.

    PubMed

    Simmons, Kimber M; Gottlieb, Peter A; Michels, Aaron W

    2016-10-01

    Type 1 diabetes (T1D) results from the immune-mediated destruction of insulin-producing β cells located within the pancreatic islets of Langerhans. The autoimmune process leads to a deficiency in insulin production and resultant hyperglycemia requiring lifelong treatment with insulin administration. T1D continues to dramatically increase in incidence, especially in young children. Substantial knowledge surrounding human disease pathogenesis exists, such that T1D is now predictable with the measurement of antibodies in the peripheral blood directed against insulin and other β cell proteins. With the ability to predict, it naturally follows that T1D should be preventable. As such, over the last two decades, numerous well-controlled clinical trials have been completed attempting to prevent diabetes onset or maintain residual β cell function after clinical onset, all providing relatively disappointing results. Here, we review the T1D prevention efforts, the current landscape of clinical therapies, and end with a discussion regarding the future outlook for preventing T1D. PMID:27558810

  7. Transthyretin constitutes a functional component in pancreatic -cell stimulus-secretion coupling

    NASA Astrophysics Data System (ADS)

    Refai, Essam; Dekki, Nancy; Yang, Shao-Nian; Imreh, Gabriela; Cabrera, Over; Yu, Lina; Yang, Guang; Norgren, Svante; Rössner, Sophia M.; Inverardi, Luca; Ricordi, Camillo; Olivecrona, Gunilla; Andersson, Mats; Jörnvall, Hans; Berggren, Per-Olof; Juntti-Berggren, Lisa

    2005-11-01

    Transthyretin (TTR) is a transport protein for thyroxine and, in association with retinol-binding protein, for retinol, mainly existing as a tetramer in vivo. We now demonstrate that TTR tetramer has a positive role in pancreatic -cell stimulus-secretion coupling. TTR promoted glucose-induced increases in cytoplasmic free Ca2+ concentration ([Ca2+]i) and insulin release. This resulted from a direct effect on glucose-induced electrical activity and voltage-gated Ca2+ channels. TTR also protected against -cell apoptosis. The concentration of TTR tetramer was decreased, whereas that of a monomeric form was increased in sera from patients with type 1 diabetes. The monomer was without effect on glucose-induced insulin release and apoptosis. Thus, TTR tetramer constitutes a component in normal -cell function. Conversion of TTR tetramer to monomer may be involved in the development of -cell failure/destruction in type 1 diabetes. type 1 diabetes | Ca2+ channels | insulin release | β-cell signal transduction | apoptosis


  8. Proteasome inhibitors, including curcumin, improve pancreatic β-cell function and insulin sensitivity in diabetic mice

    PubMed Central

    Weisberg, S; Leibel, R; Tortoriello, D V

    2016-01-01

    Background: Type 2 diabetes stems from obesity-associated insulin resistance, and in the genetically susceptible, concomitant pancreatic β-cell failure can occur, which further exacerbates hyperglycemia. Recent work by our group and others has shown that the natural polyphenol curcumin attenuates the development of insulin resistance and hyperglycemia in mouse models of hyperinsulinemic or compensated type 2 diabetes. Although several potential downstream molecular targets of curcumin exist, it is now recognized to be a direct inhibitor of proteasome activity. We now show that curcumin also prevents β-cell failure in a mouse model of uncompensated obesity-related insulin resistance (Leprdb/db on the Kaliss background). Results: In this instance, dietary supplementation with curcumin prevented hyperglycemia, increased insulin production and lean body mass, and prolonged lifespan. In addition, we show that short-term in vivo treatment with low dosages of two molecularly distinct proteasome inhibitors celastrol and epoxomicin reverse hyperglycemia in mice with β-cell failure by increasing insulin production and insulin sensitivity. Conclusions: These studies suggest that proteasome inhibitors may prove useful for patients with diabetes by improving both β-cell function and relieving insulin resistance. PMID:27110686

  9. In vitro effects of mycophenolic acid on survival, function, and gene expression of pancreatic beta-cells.

    PubMed

    Gallo, R; Natale, M; Vendrame, F; Boggi, U; Filipponi, F; Marchetti, P; Laghi Pasini, F; Dotta, F

    2012-12-01

    Post-transplant diabetes mellitus represents an important complication of prolonged immunosuppressive treatment after solid organ transplantation. The immunosuppressive toxicity, responsible for a persistent impairment of glucose metabolism in pancreatic islet-transplanted patients, is mainly attributed to calcineurin inhibitors and steroids, while other immunosuppressive molecules (azathioprine and mycophenolic acid, MPA) are considered not to have a toxic effect. In the present study, in vitro effects of MPA have been investigated in mouse beta-cell lines (βTC-1 and βTC-6) and in purified human pancreatic islets. βTC-1, βTC-6, and human pancreatic islets were exposed to various concentrations of MPA for different times. Consequently, we evaluated the viability, the induction of apoptosis, the glucose-stimulated insulin secretion, and the expression of β-cell function genes (Isl1, Pax6, Glut-2, glucokinase) and apoptosis-related genes (Bax and Bcl2). βTC-1, βTC-6, and human islets treated, respectively, for 48 and 72 h with 15-30 nM MPA showed altered islet architecture, as compared with control cells. We observed for βTC-1 and βTC-6 almost 70% reduction in cell viability; three to sixfold induction of TUNEL/apoptotic-positive cells quantified by FACS analysis. A twofold increase in apoptotic cells was observed in human islets after MPA exposure associated with strong inhibition of glucose-stimulated insulin secretion. Furthermore, we showed significant down-regulation of gene expression of molecules involved in β-cell function and increase rate between Bax/Bcl2. Our data demonstrate that MPA has an in vitro diabetogenic effect interfering at multiple levels with survival and function of murine and human pancreatic β-cells. PMID:22249339

  10. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez Muñoz, J Enrique

    2015-09-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the treatment of symptoms and complications, mainly pain and pancreatic exocrine insufficiency, and the diagnosis and therapy of autoimmune pancreatitis. The multimodal dynamic endoscopic ultrasound-guided secretin-stimulated evaluation of the pancreas provides relevant morphological and functional information for the diagnosis of chronic pancreatitis at early stages. Extracorporeal shock wave lithotripsy in patients with calcifying pancreatitis and endoscopic pancreatic stent placement are effective alternatives for pain therapy in patients with chronic pancreatitis. Presence of pancreatic exocrine insufficiency in patients with chronic pancreatitis is associated with a significantly increase of mortality rate. Despite that, pancreatic enzyme replacement therapy is not prescribed in the majority of patients with pancreatic exocrine insufficiency, or it is prescribed at a low dose. The newly developed and commercialized needles for endoscopic ultrasound-guided pancreatic biopsy are effective in retrieving appropriate tissue samples for the histological diagnosis of autoimmune pancreatitis. Maintenance therapy with azathioprine is effective and safe to prevent relapses in patients with autoimmune pancreatitis. PMID:26520201

  11. The value of KRAS mutation testing with CEA for the diagnosis of pancreatic mucinous cysts

    PubMed Central

    Kadayifci, Abdurrahman; Al-Haddad, Mohammad; Atar, Mustafa; Dewitt, John M.; Forcione, David G.; Sherman, Stuart; Casey, Brenna W.; Fernandez-del Castillo, Carlos; Schmidt, C. Max; Pitman, Martha B.; Brugge, William R.

    2016-01-01

    Background and aims: Pancreatic cyst fluid (PCF) CEA has been shown to be the most accurate preoperative test for detection of cystic mucinous neoplasms (CMNs). This study aimed to assess the added value of PCF KRAS mutational analysis to CEA for diagnosis of CMNs. Patients and methods: This is a retrospective study of prospectively collected endoscopic ultrasonography (EUS) fine-needle aspiration (FNA) data. KRAS mutation was determined by direct sequencing or equivalent methods. Cysts were classified histologically (surgical cohort) or by clinical (EUS or FNA) findings (clinical cohort). Performance characteristics of KRAS, CEA and their combination for detection of a cystic mucinous neoplasm (CMN) and malignancy were calculated. Results: The study cohort consisted of 943 patients: 147 in the surgical cohort and 796 in the clinical cohort. Overall, KRAS and CEA each had high specificity (100 % and 93.2 %), but low sensitivity (48.3 % and 56.3 %) for the diagnosis of a CMN. The positivity of KRAS or CEA increased the diagnostic accuracy (80.8 %) and AUC (0.84) significantly compared to KRAS (65.3 % and 0.74) or CEA (65.8 % and 0.74) alone, but only in the clinical cohort (P < 0.0001 for both). KRAS mutation was significantly more frequent in malignant CMNs compared to histologically confirmed non-malignant CMNs (73 % vs. 37 %, P = 0.001). The negative predictive value of KRAS mutation was 77.6 % in differentiating non-malignant cysts. Conclusions: The detection of a KRAS mutation in PCF is a highly specific test for mucinous cysts. It outperforms CEA for sensitivity in mucinous cyst diagnosis, but the data does not support its routine use. PMID:27092317

  12. Pancreatic Cancer

    MedlinePlus

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  13. Maintaining human fetal pancreatic stellate cell function and proliferation require β1 integrin and collagen I matrix interactions

    PubMed Central

    Chen, Bijun; Li, Jinming; Fellows, George F.; Sun, Zilin; Wang, Rennian

    2015-01-01

    Pancreatic stellate cells (PaSCs) are cells that are located around the acinar, ductal, and vasculature tissue of the rodent and human pancreas, and are responsible for regulating extracellular matrix (ECM) turnover and maintaining the architecture of pancreatic tissue. This study examines the contributions of integrin receptor signaling in human PaSC function and survival. Human PaSCs were isolated from pancreata collected during the 2nd trimester of pregnancy and identified by expression of stellate cell markers, ECM proteins and associated growth factors. Multiple integrins are found in isolated human PaSCs, with high levels of β1, α3 and α5. Cell adhesion and migration assays demonstrated that human PaSCs favour collagen I matrix, which enhanced PaSC proliferation and increased TGFβ1, CTGF and α3β1 integrin. Significant activation of FAK/ERK and AKT signaling pathways, and up-regulation of cyclin D1 protein levels, were observed within PaSCs cultured on collagen I matrix. Blocking β1 integrin significantly decreased PaSC adhesion, migration and proliferation, further complementing the aforementioned findings. This study demonstrates that interaction of β1 integrin with collagen I is required for the proliferation and function of human fetal PaSCs, which may contribute to the biomedical engineering of the ECM microenvironment needed for the efficient regulation of pancreatic development. PMID:26062655

  14. Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD

    PubMed Central

    Cortez, Eliane; Gladh, Hanna; Braun, Sebastian; Bocci, Matteo; Cordero, Eugenia; Björkström, Niklas K.; Miyazaki, Hideki; Michael, Iacovos P.; Eriksson, Ulf; Folestad, Erika; Pietras, Kristian

    2016-01-01

    Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis. PMID:26831065

  15. Functional improvement of porcine neonatal pancreatic cell clusters via conformal encapsulation using an air-driven encapsulator

    PubMed Central

    Park, Sol Ji; Shin, Soojeong; Koo, Ok Jae; Moon, Joon Ho; Jang, Goo; Ahn, Curie

    2012-01-01

    Transplantation of islet cells into diabetic patients is a promising therapy, provided that the islet cells are able to evade host immune rejection. With improved islet viability, this strategy may effectively reverse diabetes. We applied 2% calcium alginate to generate small and large capsules to encapsulate porcine neonatal pancreatic cell clusters (NPCCs) using an air-driven encapsulator. After encapsulation, the viability was assessed at 1, 4, 7, 14 and 28 days and secretion of functional insulin in response to glucose stimulation were tested at days 14 and 28. Selective permeability of the small alginate capsules was confirmed using various sizes of isothiocyanate-labeled dextran (FITC-dextran). Encapsulation of NPCCs was performed without islet protrusion in the small and large capsules. The viability of NPCCs in all experimental groups was greater than 90% at day 1 and then gradually decreased after day 7. The NPCCs encapsulated in large capsules showed significantly lower viability (79.50 ± 2.88%) than that of naïve NPCCs and NPCCs in small capsule (86.83 ± 2.32%, 87.67 ± 2.07%, respectively) at day 7. The viability of naïve NPCCs decreased rapidly at day 14 (75.67 ± 1.75%), whereas the NPCCs encapsulated in small capsules maintained (82.0 ± 2.19%). After 14 and 28 days NPCCs' function in small capsules (2.67 ± 0.09 and 2.13 ± 0.09) was conserved better compared to that of naïve NPCCs (2.04 ± 0.25 and 1.53 ± 0.32, respectively) and NPCCs in large capsules (2.04 ± 0.34 and 1.13 ± 0.10, respectively), as assessed by a stimulation index. The small capsules also demonstrated selective permeability. With this encapsulation technique, small capsules improved the viability and insulin secretion of NPCCs without islet protrusion. PMID:22020445

  16. 14 CFR 35.40 - Functional test.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... the endurance test (§ 35.39) must be used in the functional tests and must be driven by a representative engine on a test stand or on an airplane. The propeller must complete these tests without evidence of failure or malfunction. This test may be combined with the endurance test for accumulation...

  17. Track/train dynamics test procedure transfer function test

    NASA Technical Reports Server (NTRS)

    Vigil, R. A.

    1975-01-01

    A transfer function vibration test was made on an 80 ton open hopper freight car in an effort to obtain validation data on the car's nonlinear elastic model. Test configuration, handling, test facilities, test operations, and data acquisition/reduction activities necessary to meet the conditions of test requirements are given.

  18. Pancreatic Cancer Risk Factors

    MedlinePlus

    ... age at the time of diagnosis is 71. Gender Men are slightly more likely to develop pancreatic ... of these syndromes can be found by genetic testing. For more information on genetic testing, see Can ...

  19. Nicotinamide-functionalized multiwalled carbon nanotubes increase insulin production in pancreatic beta cells via MIF pathway

    PubMed Central

    Ilie, Ioana; Ilie, Razvan; Mocan, Teodora; Tabaran, Flaviu; Iancu, Cornel; Mocan, Lucian

    2013-01-01

    Recent data in the literature support the role of nicotinamide (NA) as a pharmacologic agent that stimulates pancreatic beta-cells to produce insulin in vitro. There are data showing that carbon nanotubes may be useful in initiating and maintaining cellular metabolic responses. This study shows that administration of multiwalled carbon nanotubes (MWCNTs) functionalized with nicotinamide (NA-MWCNTs) leads to significant insulin production compared with individual administration of NA, MWCNTs, and a control solution. Treatment of 1.4E7 cells for 30 minutes with NA-MWCNTs at concentrations ranging from 1 mg/L to 20 mg/L resulted in significantly increased insulin release (0.18 ± 0.026 ng/mL for 1 mg/L, 0.21 ± 0.024 ng/mL for 5 mg/L, and 0.27 ± 0.028 ng/mL for 20 mg/L). Thus, compared with cells treated with NA only (0.1 ± 0.01 ng/mL for 1 mg/L, 0.12 ± 0.017 ng/mL for 5 mg/L, and 0.17 ± 0.01 ng/mL for 20 mg/L) we observed a significant positive effect on insulin release in cells treated with NA-MWCNTs. The results were confirmed using flow cytometry, epifluorescence microscopy combined with immunochemistry staining, and enzyme-linked immunosorbent assay techniques. In addition, using immunofluorescence microscopy techniques, we were able to demonstrate that MWCNTs enhance insulin production via the macrophage migration inhibitory factor pathway. The application and potential of NA combined with MWCNTs as an antidiabetic agent may represent the beginning of a new chapter in the nanomediated treatment of diabetes mellitus. PMID:24039418

  20. What Are Lung Function Tests?

    MedlinePlus

    ... COPD How the Lungs Work Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... caused by conditions such as pulmonary fibrosis and sarcoidosis (sar-koy-DOE-sis). Also, these tests might ...

  1. Functional Assays for Neurotoxicity Testing

    EPA Science Inventory

    Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral ...

  2. Functional Assays for Neurotoxicity Testing*

    EPA Science Inventory

    Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral ...

  3. First Identification of the Toxicity of Microcystins on Pancreatic Islet Function in Humans and the Involved Potential Biomarkers.

    PubMed

    Zhao, Yanyan; Xue, Qingju; Su, Xiaomei; Xie, Liqiang; Yan, Yunjun; Wang, Lixiao; Steinman, Alan D

    2016-03-15

    Microcystins (MCs) produced by cyanobacteria have been recognized as a major public health threat. However, the toxicity of MCs to humans is still largely unknown. In this study, we examined the changes in pancreatic islet function in fishers exposed to ambient levels of MCs at Lake Taihu and, using a mouse model, explored the molecular mechanisms involved in toxicity. MCs content in the serum of fishers tested positive, with a range from 0.10 to 0.64 μg/L. Both lower blood insulin levels (2.26 ± 0.96 μIU/mL) and impaired fasting glucose were found in participants from the Meiliang Bay area in Lake Taihu, where MC-LR levels were substantially greater than the MC threshold established by WHO for drinking water. Animal experiments showed that glucose level increased by 27.9% in mice exposed to 5 μg/kg bw and decreased by 41.5% in mice exposed to 20 μg/kg bw. Blood insulin levels declined by 21.9% and 56.2% in mice exposed to 5 and 20 μg/kg bw MC-LR, respectively, which was consistent with the results observed in fishers. Furthermore, the diabetes gene pdx1 and several other proteins (such as Ppp3ca, Ide, Marcks, Pgk1, Suclg1, Ndufs4) involved in insulin secretion were identified for the first time in mice following MC-LR exposure; these biomarkers were considered responsible for MC-LR induced islet dysfunction. This study suggests that subchronic exposure to environmental levels of MCs may increase the risk of the occurrence of diabetes in humans. PMID:26859764

  4. Stable yeast transformants that secrete functional. cap alpha. -amylase encoded by cloned mouse pancreatic cDNA

    SciTech Connect

    Filho, S.A.; Galembeck, E.V.; Faria, J.B.; Frascino, A.C.S.

    1986-04-01

    Mouse pancreatic ..cap alpha..-amylase complementary DNA was inserted into a yeast shuttle vector after the Saccharomyces cerevisiae MF..cap alpha..1 promoter and secretion signals coding sequences. When transformed with the recombinant plasmid, S. cerevisiae cells were able to synthesize and secrete functional ..cap alpha..-amylase, efficiently hydrolyzing starch present in the culture medium. Stable amylolytic cells were obtained from different yeast strains. This work represents a significant step towards producing yeast that can convert starchy materials directly to ethanol.

  5. Metformin Plays a Dual Role in MIN6 Pancreatic β Cell Function through AMPK-dependent Autophagy

    PubMed Central

    Jiang, Yingling; Huang, Wei; Wang, Jing; Xu, Zhipeng; He, Jieyu; Lin, Xiaohong; Zhou, Zhiguang; Zhang, Jingjing

    2014-01-01

    Metformin improves insulin sensitivity in insulin sensitive tissues such as liver, muscle and fat. However, the functional roles and the underlying mechanism of metformin action in pancreatic β cells remain elusive. Here we show that, under normal growth condition, metformin suppresses MIN6 β cell proliferation and promotes apoptosis via an AMPK-dependent and autophagy-mediated mechanism. On the other hand, metformin protects MIN6 cells against palmitic acid (PA)-induced apoptosis. Our findings indicate that metformin plays a dual role in β cell survival and overdose of this anti-diabetic drug itself may lead to potential β cell toxicity. PMID:24644425

  6. HEALTH SIGNIFICANCE OF PULMONARY FUNCTION TESTS

    EPA Science Inventory

    As the sensitivity and precision of functional tests improves, we become increasingly able to measure responses to pollutant exposures with little, if any, demonstrable health significance. Proper interpretation of such functional responses generally requires an ability to evalua...

  7. Integrative fascial release and functional testing.

    PubMed

    Hammer, W

    2000-03-01

    Soft tissue techniques, including Integrative Myofascial Release (IFR) can be more effective if the area of treatment can be determined by functional testing. The patient's source of pain may not necessarily be located at the area of complaint and functional testing helps in pinpointing the source. Post-treatment functional testing will provide feedback to both the patient and the doctor as to whether the technique was effective. This paper will describe some typical functional tests and treatment using IFR of the posterior cervical/thoracolumbar fascia. PMID:17987166

  8. Increased androgen levels in rats impair glucose-stimulated insulin secretion through disruption of pancreatic beta cell mitochondrial function.

    PubMed

    Wang, Hongdong; Wang, Xiaping; Zhu, Yunxia; Chen, Fang; Sun, Yujie; Han, Xiao

    2015-11-01

    Although insulin resistance is recognized to contribute to the reproductive and metabolic phenotypes of polycystic ovary syndrome (PCOS), pancreatic beta cell dysfunction plays an essential role in the progression from PCOS to the development of type 2 diabetes. However, the role of insulin secretory abnormalities in PCOS has received little attention. In addition, the precise changes in beta cells and the underlying mechanisms remain unclear. In this study, we therefore attempted to elucidate potential mechanisms involved in beta cell alterations in a rat model of PCOS. Glucose-induced insulin secretion was measured in islets isolated from DHT-treated and control rats. Oxygen consumption rate (OCR), ATP production, and mitochondrial copy number were assayed to evaluate mitochondrial function. Glucose-stimulated insulin secretion is significantly decreased in islets from DHT-treated rats. On the other hand, significant reductions are observed in the expression levels of several key genes involved in mitochondrial biogenesis and in mitochondrial OCR and ATP production in DHT-treated rat islets. Meanwhile, we found that androgens can directly impair beta cell function by inducing mitochondrial dysfunction in vitro in an androgen receptor dependent manner. For the first time, our study demonstrates that increased androgens in female rats can impair glucose-stimulated insulin secretion partly through disruption of pancreatic beta cell mitochondrial function. This work has significance for hyperandrogenic women with PCOS: excess activation of the androgen receptor by androgens may provoke beta cell dysfunction via mitochondrial dysfunction. PMID:26348137

  9. Functional and Structural Roles of the Cys14-Cys38 Disulfide of Bovine Pancreatic Trypsin Inhibitor

    PubMed Central

    Zakharova, Elena; Horvath, Martin P.; Goldenberg, David P.

    2008-01-01

    The disulfide bond between Cys14 and Cys38 of bovine pancreatic trypsin inhibitor (BPTI) lies on the surface of the inhibitor and forms part of the protease binding region. The functional properties of three variants lacking this disulfide, with one or both of the Cys residues replaced with Ser, were examined, and x-ray crystal structures of the complexes with bovine trypsin were determined and refined to the 1.58 Å resolution limit. The crystal structure of the complex formed with the mutant with both Cys residues replaced was nearly identical to that of the complex containing the wild-type protein, with the Ser oxygen atoms positioned to replace the disulfide bond with a hydrogen bond. The two structures of the complexes with single replacements displayed small local perturbations with alternate conformations of the Ser side chains. Despite the absence of the disulfide bond, the crystallographic temperature factors show no evidence of increased flexibility in the complexes with the mutant inhibitors. All three of the variants were cleaved by trypsin more rapidly than the wild-type inhibitor, by as much as 10,000-fold, indicating that the covalent constraint normally imposed by the disulfide contributes to the remarkable resistance to hydrolysis displayed by the wild-type protein. The rates of hydrolysis display an unusual dependence on pH over the range from 3.5 to 8, decreasing at the more alkaline values, as compared to the increased hydrolysis rates for normal substrates under these conditions. These observations can be accounted for by a model for inhibition in which an acyl-enzyme intermediate forms at a significant rate but is rapidly converted back to the enzyme-inhibitor complex by nucleophilic attack by the newly created amino group. The model suggests that a lack of flexibility in the acyl-enzyme intermediate, rather than the enzyme-inhibitor complex, may be a key factor in the ability of BPTI and similar inhibitors to resist hydrolysis. PMID:18692070

  10. Dual role of Ski in pancreatic cancer cells: tumor-promoting versus metastasis-suppressive function.

    PubMed

    Wang, Peng; Chen, Zhen; Meng, Zhi-Qiang; Fan, Jie; Luo, Jian-Min; Liang, Wang; Lin, Jun-Hua; Zhou, Zhen-Hua; Chen, Hao; Wang, Kun; Shen, Ye-Hua; Xu, Zu-De; Liu, Lu-Ming

    2009-09-01

    Ski used to be defined as an oncogene that contributes to the resistance of tumor cells to transforming growth factor-beta (TGF-beta)-induced growth arrest. As TGF-beta has a dual effect on tumor growth with both tumor-suppressing and -promoting activity depending on the stage of carcinogenesis and the cell type, the precise role of Ski in carcinogenesis remains unclear. In this study, we show that downregulation of Ski through lentivirus-mediated RNA interference decreases tumor growth both in vitro and in vivo, yet promotes cell invasiveness in vitro, and lung metastasis in vivo in the pancreatic cancer cell line SW1990, which contain wild-type Smad4 expression, and the BxPC3 cell line, which is Smad4 deficient. We also show that the downregulation of Ski increases TGF-beta-induced transcriptional activity, which is associated with increased TGF-beta-dependent Smad2/3 phosphorylation, and results in an altered expression profile of TGF-beta-inducible genes involved in metastasis, angiogenesis and cell proliferation and epithelial-mesenchymal transition. Immunohistochemical analysis of specimens from 71 patients with pancreatic adenocarcinoma showed a significant association between overexpression of Ski and decreased patient survival time (P = 0.0024). Our results suggest that Ski may act as a tumor proliferation-promoting factor or as a metastatic suppressor in human pancreatic cancer. PMID:19546161

  11. Pancreatic β-Cell Adaptive Plasticity in Obesity Increases Insulin Production but Adversely Affects Secretory Function.

    PubMed

    Alarcon, Cristina; Boland, Brandon B; Uchizono, Yuji; Moore, Patrick C; Peterson, Bryan; Rajan, Suryalekha; Rhodes, Olivia S; Noske, Andrew B; Haataja, Leena; Arvan, Peter; Marsh, Bradly J; Austin, Jotham; Rhodes, Christopher J

    2016-02-01

    Pancreatic β-cells normally produce adequate insulin to control glucose homeostasis, but in obesity-related diabetes, there is a presumed deficit in insulin production and secretory capacity. In this study, insulin production was assessed directly in obese diabetic mouse models, and proinsulin biosynthesis was found to be contrastingly increased, coupled with a significant expansion of the rough endoplasmic reticulum (without endoplasmic reticulum stress) and Golgi apparatus, increased vesicular trafficking, and a depletion of mature β-granules. As such, β-cells have a remarkable capacity to produce substantial quantities of insulin in obesity, which are then made available for immediate secretion to meet increased metabolic demand, but this comes at the price of insulin secretory dysfunction. Notwithstanding, it can be restored. Upon exposing isolated pancreatic islets of obese mice to normal glucose concentrations, β-cells revert back to their typical morphology with restoration of regulated insulin secretion. These data demonstrate an unrealized dynamic adaptive plasticity of pancreatic β-cells and underscore the rationale for transient β-cell rest as a treatment strategy for obesity-linked diabetes. PMID:26307586

  12. ELEFUNT. Tests of Fortran Elementary Functions

    SciTech Connect

    Cody, W.J.

    1980-03-14

    ELEFUNT is an aggressive test of one or more of the elementary function subroutines generally supplied with the support library accompanying a FORTRAN compiler. Functions tested are ALOG/ALOG10, ASIN/ACOS, ATAN, EXP, POWER, SIN/COS, SINH/COSH, SQRT, TAN/COTAN, and TANH.

  13. Improving function and survival of pancreatic islets by endogenous production of glucagon-like peptide 1 (GLP-1).

    PubMed

    Wideman, Rhonda D; Yu, Irene L Y; Webber, Travis D; Verchere, C Bruce; Johnson, James D; Cheung, Anthony T; Kieffer, Timothy J

    2006-09-01

    Glucagon-like peptide 1 (GLP-1) is a hormone that has received significant attention as a therapy for diabetes because of its ability to stimulate insulin biosynthesis and release and to promote growth and survival of insulin-producing beta cells. While GLP-1 is produced from the proglucagon precursor by means of prohormone convertase (PC) 1/3 activity in enteroendocrine L cells, the same precursor is differentially processed by PC2 in pancreatic islet alpha cells to release glucagon, leaving GLP-1 trapped within a larger fragment with no known function. We hypothesized that we could induce GLP-1 production directly within pancreatic islets by means of delivery of PC1/3 and, further, that this intervention would improve the viability and function of islets. Here, we show that adenovirus-mediated expression of PC1/3 in alpha cells increases islet GLP-1 secretion, resulting in improved glucose-stimulated insulin secretion and enhanced survival in response to cytokine treatment. PC1/3 expression in alpha cells also improved performance after islet transplantation in a mouse model of type 1 diabetes, possibly by enhancing nuclear Pdx1 and insulin content of islet beta cells. These results demonstrate a unique strategy for liberating GLP-1 from directly within the target organ and highlight the potential for up-regulating islet GLP-1 production as a means of treating diabetes. PMID:16938896

  14. Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic β-cell function

    PubMed Central

    Jia, Shiqi; Ivanov, Andranik; Blasevic, Dinko; Müller, Thomas; Purfürst, Bettina; Sun, Wei; Chen, Wei; Poy, Matthew N; Rajewsky, Nikolaus; Birchmeier, Carmen

    2015-01-01

    Key transcription factors control the gene expression program in mature pancreatic β-cells, but their integration into regulatory networks is little understood. Here, we show that Insm1, Neurod1 and Foxa2 directly interact and together bind regulatory sequences in the genome of mature pancreatic β-cells. We used Insm1 ablation in mature β-cells in mice and found pronounced deficits in insulin secretion and gene expression. Insm1-dependent genes identified previously in developing β-cells markedly differ from the ones identified in the adult. In particular, adult mutant β-cells resemble immature β-cells of newborn mice in gene expression and functional properties. We defined Insm1, Neurod1 and Foxa2 binding sites associated with genes deregulated in Insm1 mutant β-cells. Remarkably, combinatorial binding of Insm1, Neurod1 and Foxa2 but not binding of Insm1 alone explained a significant fraction of gene expression changes. Human genomic sequences corresponding to the murine sites occupied by Insm1/Neurod1/Foxa2 were enriched in single nucleotide polymorphisms associated with glycolytic traits. Thus, our data explain part of the mechanisms by which β-cells maintain maturity: Combinatorial Insm1/Neurod1/Foxa2 binding identifies regulatory sequences that maintain the mature gene expression program in β-cells, and disruption of this network results in functional failure. PMID:25828096

  15. Joe Doupe lecture: emerging strategies for the preservation of pancreatic beta-cell function in early type 2 diabetes.

    PubMed

    Retnakaran, Ravi

    2014-01-01

    A fundamental problem in the clinical management of type 2 diabetes is the inability to prevent the ongoing deterioration of pancreatic beta-cell function over time that underlies the chronic progressive nature of this condition. Importantly, beta-cell dysfunction has both reversible and irreversible components. Furthermore, the amelioration of reversible beta-cell dysfunction through the early institution of short-term insulin-based therapy has emerged as a strategy that can yield temporary remission of type 2 diabetes. In this context, we have forwarded a novel therapeutic paradigm consisting of initial induction therapy to improve beta-cell function early in the course of diabetes followed by maintenance therapy aimed at preserving this beneficial beta-cell effect. Ultimately, this approach may yield an optimized therapeutic strategy for the durable preservation of beta-cell function and consequent modification of the natural history of type 2 diabetes. PMID:25618275

  16. Pancreatic pseudocyst

    MedlinePlus

    ... It may also contain tissue from the pancreas, pancreatic enzymes, and blood. ... located behind the stomach. It produces chemicals (called enzymes) ... Pancreatic pseudocysts most often develop after an episode of ...

  17. Pancreatic abscess

    MedlinePlus

    Most people with pancreatic abscesses have had pancreatitis. However, the complication often takes 7 or more days to develop. Signs of an abscess can be seen on: CT scan of the abdomen MRI of the abdomen Ultrasound of the abdomen

  18. Pancreatitis - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100149.htm Pancreatitis - series To use the sharing features on this ... A.M. Editorial team. Related MedlinePlus Health Topics Pancreatitis A.D.A.M., Inc. is accredited by ...

  19. Loss of Periostin Results in Impaired Regeneration and Pancreatic Atrophy after Cerulein-Induced Pancreatitis.

    PubMed

    Hausmann, Simone; Regel, Ivonne; Steiger, Katja; Wagner, Nadine; Thorwirth, Manja; Schlitter, Anna M; Esposito, Irene; Michalski, Christoph W; Friess, Helmut; Kleeff, Jörg; Erkan, Mert

    2016-01-01

    The extracellular matrix molecule periostin (POSTN, encoded by POSTN), which is secreted by activated pancreatic stellate cells, has important functions in chronic pancreatitis and pancreatic cancer. However, the role of POSTN in acute pancreatitis and subsequent regeneration processes has not been addressed so far. We analyzed the function of POSTN in pancreatic exocrine regeneration after the induction of a severe acute pancreatitis. Postn-deficient mice and wild-type control animals received repetitive cerulein injections, and a detailed histologic analysis of pancreatic tissues was performed. Although there was no difference in pancreatitis severity in the acute inflammatory phase, the recovery of the exocrine pancreas was massively impaired in Postn-deficient mice. Loss of Postn expression was accompanied by strong pancreatic atrophy and acinar-to-adipocyte differentiation, which was also reflected in gene expression patterns. Our data suggest that POSTN is a crucial factor for proper exocrine lineage-specific regeneration after severe acute pancreatitis. PMID:26632158

  20. Binomial test statistics using Psi functions

    SciTech Connect

    Bowman, Kimiko o

    2007-01-01

    For the negative binomial model (probability generating function (p + 1 - pt){sup -k}) a logarithmic derivative is the Psi function difference {psi}(k + x) - {psi}(k); this and its derivatives lead to a test statistic to decide on the validity of a specified model. The test statistic uses a data base so there exists a comparison available between theory and application. Note that the test function is not dominated by outliers. Applications to (i) Fisher's tick data, (ii) accidents data, (iii) Weldon's dice data are included.

  1. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

    SciTech Connect

    Kover, Karen; Yan, Yun; Tong, Pei Ying; Watkins, Dara; Li, Xiaoyu; Tasch, James; Hager, Melissa; Clements, Mark; Moore, Wayne V.

    2015-06-19

    Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H{sub 2}O{sub 2} assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H{sub 2}O{sub 2} levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose

  2. Pancreatitis activates pancreatic apelin-APJ axis in mice

    PubMed Central

    Han, Song; Englander, Ella W.; Gomez, Guillermo A.; Aronson, Judith F.; Rastellini, Cristiana; Garofalo, R. P.; Kolli, Deepthi; Quertermous, Thomas; Kundu, Ramendra

    2013-01-01

    Pancreatitis is classified into acute pancreatitis (AP) and chronic pancreatitis (CP). Apelin, a small regulatory peptide, is the endogenous ligand for the APJ receptor. Apelin and APJ are expressed in the pancreas. The aims of this study were to examine whether apelin influences the inflammatory and fibrosis responses to pancreatitis in mice and to identify mechanisms behind apelin's activities. Supramaximal cerulein induction of AP or CP caused significant (P < 0.05) elevations in pancreatic apelin and APJ expression. Levels declined during the recovery phases. In apelin gene-knockout mice with pancreatitis, pancreatic neutrophil invasion and myeloperoxidase activity were enhanced significantly, and apelin treatment suppressed both. Apelin exposure reduced CP-induced elevations of extracellular matrix-associated proteins. Apelin inhibited PDGF-simulated connective tissue growth factor production and proliferation of pancreatic stellate cells (PSCs). Serum granulocyte colony-stimulating factor and keratinocyte cytokine levels were higher in apelin gene-knockout than wild-type mice with pancreatitis. Apelin reduced AP- and CP-induced elevations in pancreatic NF-κB activation. Together, these findings imply that the pancreatic apelin-APJ system functions to curb the inflammatory and fibrosis responses during pancreatitis. Furthermore, findings suggest that apelin reduces inflammation and fibrosis by reducing neutrophil recruitment and PSC activity. Inhibition of neutrophil invasion may be mediated by reduced keratinocyte cytokine and granulocyte colony-stimulating factor secretion. Apelin-induced reductions in PSC proliferation and connective tissue growth factor production are putative mechanisms underlying apelin's inhibition of extracellular matrix production. The apelin-associated changes in NF-κB binding may be linked to apelin's regulation of pancreatic inflammatory and fibrosis responses during pancreatitis. PMID:23681476

  3. Pancreatitis activates pancreatic apelin-APJ axis in mice.

    PubMed

    Han, Song; Englander, Ella W; Gomez, Guillermo A; Aronson, Judith F; Rastellini, Cristiana; Garofalo, R P; Kolli, Deepthi; Quertermous, Thomas; Kundu, Ramendra; Greeley, George H

    2013-07-15

    Pancreatitis is classified into acute pancreatitis (AP) and chronic pancreatitis (CP). Apelin, a small regulatory peptide, is the endogenous ligand for the APJ receptor. Apelin and APJ are expressed in the pancreas. The aims of this study were to examine whether apelin influences the inflammatory and fibrosis responses to pancreatitis in mice and to identify mechanisms behind apelin's activities. Supramaximal cerulein induction of AP or CP caused significant (P < 0.05) elevations in pancreatic apelin and APJ expression. Levels declined during the recovery phases. In apelin gene-knockout mice with pancreatitis, pancreatic neutrophil invasion and myeloperoxidase activity were enhanced significantly, and apelin treatment suppressed both. Apelin exposure reduced CP-induced elevations of extracellular matrix-associated proteins. Apelin inhibited PDGF-simulated connective tissue growth factor production and proliferation of pancreatic stellate cells (PSCs). Serum granulocyte colony-stimulating factor and keratinocyte cytokine levels were higher in apelin gene-knockout than wild-type mice with pancreatitis. Apelin reduced AP- and CP-induced elevations in pancreatic NF-κB activation. Together, these findings imply that the pancreatic apelin-APJ system functions to curb the inflammatory and fibrosis responses during pancreatitis. Furthermore, findings suggest that apelin reduces inflammation and fibrosis by reducing neutrophil recruitment and PSC activity. Inhibition of neutrophil invasion may be mediated by reduced keratinocyte cytokine and granulocyte colony-stimulating factor secretion. Apelin-induced reductions in PSC proliferation and connective tissue growth factor production are putative mechanisms underlying apelin's inhibition of extracellular matrix production. The apelin-associated changes in NF-κB binding may be linked to apelin's regulation of pancreatic inflammatory and fibrosis responses during pancreatitis. PMID:23681476

  4. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    PubMed Central

    Nandy, Debashis; Mukhopadhyay, Debabrata

    2011-01-01

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed. PMID:24212642

  5. PKD signaling and pancreatitis

    PubMed Central

    Yuan, Jingzhen; Pandol, Stephen J.

    2016-01-01

    Background Acute pancreatitis is a serious medical disorder with no current therapies directed to the molecular pathogenesis of the disorder. Inflammation, inappropriate intracellular activation of digestive enzymes, and parenchymal acinar cell death by necrosis are the critical pathophysiologic processes of acute pancreatitis. Thus, it is necessary to elucidate the key molecular signals that mediate these pathobiologic processes and develop new therapeutic strategies to attenuate the appropriate signaling pathways in order to improve outcomes for this disease. A novel serine/threonine protein kinase D (PKD) family has emerged as key participants in signal transduction, and this family is increasingly being implicated in the regulation of multiple cellular functions and diseases. Methods This review summarizes recent findings of our group and others regarding the signaling pathway and the biological roles of the PKD family in pancreatic acinar cells. In particular, we highlight our studies of the functions of PKD in several key pathobiologic processes associated with acute pancreatitis in experimental models. Results Our findings reveal that PKD signaling is required for NF-κB activation/inflammation, intracellular zymogen activation, and acinar cell necrosis in rodent experimental pancreatitis. Novel small-molecule PKD inhibitors attenuate the severity of pancreatitis in both in vitro and in vivo experimental models. Further, this review emphasizes our latest advances in the therapeutic application of PKD inhibitors to experimental pancreatitis after the initiation of pancreatitis. Conclusions These novel findings suggest that PKD signaling is a necessary modulator in key initiating pathobiologic processes of pancreatitis, and that it constitutes a novel therapeutic target for treatments of this disorder. PMID:26879861

  6. Effects of antidiabetic agents on pancreatic beta-cell function in gestational diabetes: is there enough evidence?

    PubMed

    Tura, Andrea; Göbl, Christian; Pacini, Giovanni

    2016-01-01

    Gestational diabetes mellitus (GDM) is typically characterized by the presence of insulin resistance. However, recent studies showed that both insulin resistance and pancreatic beta-cell function impairment may contribute to the development of type 2 diabetes in women with history of GDM. In fact, beta-cell function decline was found as significant predictor of later disease in former GDM women progressing towards type 2 diabetes. Despite the evidence of the relevance of beta-cell function quantification in GDM, a low number of studies focused on the effects of GDM treatments on beta-cell function. We briefly present the evidence of the effects on beta-cell function of pharmacological agents, as well as nutrition supplements or medical nutrition therapy, used in the management of GDM. We found that few studies reported information on beta-cell function effects in GDM, despite some agents, such as glyburide, are well known insulin secretagogues. Therefore, further studies should be carried out to clearly assess the effects on beta-cell function of the treatments in GDM women. PMID:26609764

  7. Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice

    PubMed Central

    Kuznetsova, Alexandra; Yu, Yue; Hollister-Lock, Jennifer; Opare-Addo, Lynn; Rozzo, Aldo; Sadagurski, Marianna; Norquay, Lisa; Reed, Jessica E.; El Khattabi, Ilham; Bonner-Weir, Susan; Weir, Gordon C.; Sharma, Arun; White, Morris F.

    2016-01-01

    The capacity of pancreatic β cells to maintain glucose homeostasis during chronic physiologic and immunologic stress is important for cellular and metabolic homeostasis. Insulin receptor substrate 2 (IRS2) is a regulated adapter protein that links the insulin and IGF1 receptors to downstream signaling cascades. Since strategies to maintain or increase IRS2 expression can promote β cell growth, function, and survival, we conducted a screen to find small molecules that can increase IRS2 mRNA in isolated human pancreatic islets. We identified 77 compounds, including 15 that contained a tricyclic core. To establish the efficacy of our approach, one of the tricyclic compounds, trimeprazine tartrate, was investigated in isolated human islets and in mouse models. Trimeprazine is a first-generation antihistamine that acts as a partial agonist against the histamine H1 receptor (H1R) and other GPCRs, some of which are expressed on human islets. Trimeprazine promoted CREB phosphorylation and increased the concentration of IRS2 in islets. IRS2 was required for trimeprazine to increase nuclear Pdx1, islet mass, β cell replication and function, and glucose tolerance in mice. Moreover, trimeprazine synergized with anti-CD3 Abs to reduce the progression of diabetes in NOD mice. Finally, it increased the function of human islet transplants in streptozotocin-induced (STZ-induced) diabetic mice. Thus, trimeprazine, its analogs, or possibly other compounds that increase IRS2 in islets and β cells without adverse systemic effects might provide mechanism-based strategies to prevent the progression of diabetes. PMID:27152363

  8. PULMONARY FUNCTION TESTING IN SMALL LABORATORY MAMMALS

    EPA Science Inventory

    The lung is the primary organ likely to be exposed by inhalation studies and, therefore, measurement of changes in lung function are of particular interest to the pulmonary physiologist and toxicologist. Tests of pulmonary function have been developed which can be used with small...

  9. Simultaneous pancreatic-renal transplant scintigraphy

    SciTech Connect

    Shulkin, B.L.; Dafoe, D.C.; Wahl, R.L.

    1986-12-01

    99mTc-DTPA scintigraphy was evaluated in seven patients as a technique to assess perfusion of the transplanted pancreas and kidney. Such scans provide high-quality images of both organs in both the flow phase and later phases. The radionuclide is readily available and its brief effective half-life allows repeated evaluations at short intervals. /sup 131/I-hippuran, the major radiopharmaceutical for renal transplant scintigraphy, does not allow visualization of the transplanted pancreas or evaluation of its blood supply. Although the blood glucose is a gross indicator of the function of the pancreatic allograft, pancreatic scintigraphy with 99mTc-DTPA in one case was capable of detecting graft dysfunction before elevation of the blood glucose occurred. While additional studies will be necessary to determine the predictive value of this test, 99mTc-DTPA is valuable for pancreatic-renal transplant evaluation.

  10. Pancreatic Polypeptide Inhibits Somatostatin Secretion

    PubMed Central

    Kim, Wook; Fiori, Jennifer L.; Shin, Yu-Kyong; Okun, Eitan; Kim, Jung Seok; Rapp, Peter R.; Egan, Josephine M.

    2014-01-01

    Pancreatic polypeptide (PP) is a major agonist for neuropeptide Y4 receptors (NPY4R). While NPY4R has been identified in various tissues, the cells on which it is expressed and its function in those cells has not been clearly delineated. Here we report that NPY4R is present in all somatostatin-containing cells of tissues that we tested, including pancreatic islets, duodenum, hippocampus, and hypothalamus. Its agonism by PP decreases somatostatin secretion from human islets. Mouse embryonic hippocampal (mHippo E18) cells expressed NPY4Rs and their activation by PP consistently decreased somatostatin secretion. Furthermore, central injection of PP in mice induced c-Fos immunoreactivity in somatostatin-containing cells in the hippocampus compared with PBS-injected mice. In sum, our results identify PP as a pivotal modulator of somatostatin secretion. PMID:25019573

  11. Differentiation and transplantation of functional pancreatic beta cells generated from induced pluripotent stem cells derived from a type 1 diabetes mouse model.

    PubMed

    Jeon, Kilsoo; Lim, Hyejin; Kim, Jung-Hyun; Thuan, Nguyen Van; Park, Seung Hwa; Lim, Yu-Mi; Choi, Hye-Yeon; Lee, Eung-Ryoung; Kim, Jin-Hoi; Lee, Myung-Shik; Cho, Ssang-Goo

    2012-09-20

    The nonobese diabetic (NOD) mouse is a classical animal model for autoimmune type 1 diabetes (T1D), closely mimicking features of human T1D. Thus, the NOD mouse presents an opportunity to test the effectiveness of induced pluripotent stem cells (iPSCs) as a therapeutic modality for T1D. Here, we demonstrate a proof of concept for cellular therapy using NOD mouse-derived iPSCs (NOD-iPSCs). We generated iPSCs from NOD mouse embryonic fibroblasts or NOD mouse pancreas-derived epithelial cells (NPEs), and applied directed differentiation protocols to differentiate the NOD-iPSCs toward functional pancreatic beta cells. Finally, we investigated whether the NPE-iPSC-derived insulin-producing cells could normalize hyperglycemia in transplanted diabetic mice. The NOD-iPSCs showed typical embryonic stem cell-like characteristics such as expression of markers for pluripotency, in vitro differentiation, teratoma formation, and generation of chimeric mice. We developed a method for stepwise differentiation of NOD-iPSCs into insulin-producing cells, and found that NPE-iPSCs differentiate more readily into insulin-producing cells. The differentiated NPE-iPSCs expressed diverse pancreatic beta cell markers and released insulin in response to glucose and KCl stimulation. Transplantation of the differentiated NPE-iPSCs into diabetic mice resulted in kidney engraftment. The engrafted cells responded to glucose by secreting insulin, thereby normalizing blood glucose levels. We propose that NOD-iPSCs will provide a useful tool for investigating genetic susceptibility to autoimmune diseases and generating a cellular interaction model of T1D, paving the way for the potential application of patient-derived iPSCs in autologous beta cell transplantation for treating diabetes. PMID:22512788

  12. Comparison of clinical tests of olfactory function.

    PubMed

    Reden, J; Draf, C; Frank, R A; Hummel, T

    2016-04-01

    To assess olfactory function, various measures are used in clinical routine. In this study, the Sniff Magnitude Test (SMT), a test considering the sniff response to an odor, was applied to patients with olfactory dysfunction (n = 49) and to a control group without subjective olfaction disorder (n = 21). For comparison, the validated "Sniffin' Sticks" test battery, a psychophysical olfactory test consisting of tests for phenyl ethyl alcohol odor threshold, odor discrimination, and odor identification was performed. Analyses indicated that the SMT showed significant differences between patients and controls (p = 0.003). Furthermore, results from the SMT and the "Sniffin' Sticks" correlated significantly (p < 0.001). In conclusion, the SMT appears to be a useful addition to the battery of available clinical tests to assess olfactory function. PMID:26050222

  13. Pancreatic cancer.

    PubMed

    Kamisawa, Terumi; Wood, Laura D; Itoi, Takao; Takaori, Kyoichi

    2016-07-01

    Pancreatic cancer is a highly lethal disease, for which mortality closely parallels incidence. Most patients with pancreatic cancer remain asymptomatic until the disease reaches an advanced stage. There is no standard programme for screening patients at high risk of pancreatic cancer (eg, those with a family history of pancreatic cancer and chronic pancreatitis). Most pancreatic cancers arise from microscopic non-invasive epithelial proliferations within the pancreatic ducts, referred to as pancreatic intraepithelial neoplasias. There are four major driver genes for pancreatic cancer: KRAS, CDKN2A, TP53, and SMAD4. KRAS mutation and alterations in CDKN2A are early events in pancreatic tumorigenesis. Endoscopic ultrasonography and endoscopic ultrasonography-guided fine-needle aspiration offer high diagnostic ability for pancreatic cancer. Surgical resection is regarded as the only potentially curative treatment, and adjuvant chemotherapy with gemcitabine or S-1, an oral fluoropyrimidine derivative, is given after surgery. FOLFIRINOX (fluorouracil, folinic acid [leucovorin], irinotecan, and oxaliplatin) and gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) are the treatments of choice for patients who are not surgical candidates but have good performance status. PMID:26830752

  14. Pancreatic Cancer

    PubMed Central

    Maitra, Anirban; Hruban, Ralph H.

    2009-01-01

    The past two decades have witnessed an explosion in our understanding of pancreatic cancer, and it is now clear that pancreatic cancer is a disease of inherited (germ-line) and somatic gene mutations. The genes mutated in pancreatic cancer include KRAS2, p16/CDKN2A, TP53, and SMAD4/DPC4, and these are accompanied by a substantial compendium of genomic and transcriptomic alterations that facilitate cell cycle deregulation, cell survival, invasion, and metastases. Pancreatic cancers do not arise de novo, and three distinct precursor lesions have been identified. Experimental models of pancreatic cancer have been developed in genetically engineered mice, which recapitulate the multistep progression of the cognate human disease. Although the putative cell of origin for pancreatic cancer remains elusive, minor populations of cells with stem-like properties have been identified that appear responsible for tumor initiation, metastases, and resistance of pancreatic cancer to conventional therapies. PMID:18039136

  15. Evaluation of abnormal liver function tests.

    PubMed

    Agrawal, Swastik; Dhiman, Radha K; Limdi, Jimmy K

    2016-04-01

    Incidentally detected abnormality in liver function tests is a common situation encountered by physicians across all disciplines. Many of these patients do not have primary liver disease as most of the commonly performed markers are not specific for the liver and are affected by myriad factors unrelated to liver disease. Also, many of these tests like liver enzyme levels do not measure the function of the liver, but are markers of liver injury, which is broadly of two types: hepatocellular and cholestatic. A combination of a careful history and clinical examination along with interpretation of pattern of liver test abnormalities can often identify type and aetiology of liver disease, allowing for a targeted investigation approach. Severity of liver injury is best assessed by composite scores like the Model for End Stage Liver Disease rather than any single parameter. In this review, we discuss the interpretation of the routinely performed liver tests along with the indications and utility of quantitative tests. PMID:26842972

  16. Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer.

    PubMed

    Huang, Jing; Qian, Weiping; Wang, Liya; Wu, Hui; Zhou, Hongyu; Wang, Andrew Yongqiang; Chen, Hongbo; Yang, Lily; Mao, Hui

    2016-01-01

    Engineered nanocarriers have emerged as a promising platform for cancer therapy. However, the therapeutic efficacy is limited by low drug loading efficiency, poor passive targeting to tumors, and severe systemic side effects. Herein, we report a new class of nanoconstructs based on milk protein (casein)-coated magnetic iron oxide (CNIO) nanoparticles for targeted and image-guided pancreatic cancer treatment. The tumor-targeting amino-terminal fragment (ATF) of urokinase plasminogen activator and the antitumor drug cisplatin (CDDP) were engineered on this nanoplatform. High drug loading (~25 wt%) and sustained release at physiological conditions were achieved through the exchange and encapsulation strategy. These ATF-CNIO-CDDP nanoparticles demonstrated actively targeted delivery of CDDP to orthotopic pancreatic tumors in mice. The effective accumulation and distribution of ATF-CNIO-CDDP was evidenced by magnetic resonance imaging, based on the T2-weighted contrast resulting from the specific accumulation of ATF-CNIO-CDDP in the tumor. Actively targeted delivery of ATF-CNIO-CDDP led to improved therapeutic efficacy in comparison with free CDDP and nontargeted CNIO-CDDP treatment. Meanwhile, less systemic side effects were observed in the nanocarrier-treated groups than that in the group treated with free CDDP. Hematoxylin and Eosin and Sirius Red staining of tumor sections revealed the possible disruption of stroma during the treatment with ATF-CNIO-CDDP. Overall, our results suggest that ATF-CNIO-CDDP can be an effective theranostic platform for active targeting-enhanced and image-guided cancer treatment while simultaneously reducing the systemic toxicity. PMID:27462153

  17. Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer

    PubMed Central

    Huang, Jing; Qian, Weiping; Wang, Liya; Wu, Hui; Zhou, Hongyu; Wang, Andrew Yongqiang; Chen, Hongbo; Yang, Lily; Mao, Hui

    2016-01-01

    Engineered nanocarriers have emerged as a promising platform for cancer therapy. However, the therapeutic efficacy is limited by low drug loading efficiency, poor passive targeting to tumors, and severe systemic side effects. Herein, we report a new class of nanoconstructs based on milk protein (casein)-coated magnetic iron oxide (CNIO) nanoparticles for targeted and image-guided pancreatic cancer treatment. The tumor-targeting amino-terminal fragment (ATF) of urokinase plasminogen activator and the antitumor drug cisplatin (CDDP) were engineered on this nanoplatform. High drug loading (~25 wt%) and sustained release at physiological conditions were achieved through the exchange and encapsulation strategy. These ATF-CNIO-CDDP nanoparticles demonstrated actively targeted delivery of CDDP to orthotopic pancreatic tumors in mice. The effective accumulation and distribution of ATF-CNIO-CDDP was evidenced by magnetic resonance imaging, based on the T2-weighted contrast resulting from the specific accumulation of ATF-CNIO-CDDP in the tumor. Actively targeted delivery of ATF-CNIO-CDDP led to improved therapeutic efficacy in comparison with free CDDP and nontargeted CNIO-CDDP treatment. Meanwhile, less systemic side effects were observed in the nanocarrier-treated groups than that in the group treated with free CDDP. Hematoxylin and Eosin and Sirius Red staining of tumor sections revealed the possible disruption of stroma during the treatment with ATF-CNIO-CDDP. Overall, our results suggest that ATF-CNIO-CDDP can be an effective theranostic platform for active targeting-enhanced and image-guided cancer treatment while simultaneously reducing the systemic toxicity. PMID:27462153

  18. Pulmonary function testing in small laboratory mammals.

    PubMed Central

    O'Neil, J J; Raub, J A

    1984-01-01

    The lung is the primary organ likely to be exposed by inhalation studies and, therefore, measurement of changes in lung function are of particular interest to the pulmonary physiologist and toxicologist. Tests of pulmonary function have been developed which can be used with small animals to measure spirometry (lung volumes), mechanics, distribution of ventilation, gas exchange or control of ventilation. These tests were designed on the basis of similar tests which are used in humans to diagnose and manage patients with lung disease. A major difference is that many of the measurements are performed in anesthetized animals, while human pulmonary function is usually measured in awake cooperating individuals. In addition, the measurement of respiratory events in small animals requires sensitive and rapidly responding equipment, because signals may be small and events can occur quickly. In general, the measurements described provide information on the change in normal lung function which results primarily from structural changes. These tests of pulmonary function can be repetitively and routinely accomplished and the results appear to be highly reproducible. Although some are quite sophisticated, many can be undertaken with relatively inexpensive equipment and provide useful information for toxicological testing. PMID:6434299

  19. Tyropanoate cholecystography early in the course of acute pancreatitis.

    PubMed

    Longstreth, G F; Slivka, J

    1981-01-01

    Oral cholecystography (OCG) has traditionally been delayed until several weeks after hospitalization for pancreatitis because of the putative frequent poor visualization during the acute episode. Recently, OCG with iopanoic acid was reported successful in most patients with acute pancreatitis soon after resumption of a solid diet. We evaluated OCG with sodium tyropanoate, a pharmacokinetically different contrast material, in 30 hospitalized patients with pancreatitis before resumption of solid food. It accurately evaluated the gallbladder in 24 cases (80%). Abnormal liver function tests, including mild hyperbilirubinemia, did not interfere with the examination. Consequently, 1) tyropanoate OCG adequately opacifies the gallbladder in most patients with acute pancreatitis who are fasting or taking liquids only; 2) allows gallbladder evaluation earlier than with iopanoic acid OCG; 3) is less affected by hepatic dysfunction; and 4) provides an alternative to ultrasonography. PMID:7328298

  20. Characterization of a novel functional protein in the pancreatic islet: IHoP regulation of glucagon synthesis in alpha-cells

    PubMed Central

    Oh, Seh-Hoon; Darwiche, Houda; Cho, Jae-Hyoung; Shupe, Thomas; Petersen, Bryon E.

    2011-01-01

    Objective We have identified a novel protein in bone marrow (BM)-derived insulin-producing cells (IPCs). Here we characterize this protein, hereby named Islet Homeostasis Protein (IHoP), in the pancreatic islet. Methods Detection of IHoP mRNA and protein were performed using RT-PCR, immunocytochemistry and in-situ hybridization. IHoP functions were utilizing proliferation, insulin secretion by in vitro assays, and as well as following siRNA protocols for suppression of IHoP. Results We found that IHoP did not homologue with known pancreatic hormones. IHoP expression was seen in both BM-derived IPCs and isolated pancreatic islets. Immunohistochemistry on pancreatic islet revealed that IHoP localized to the glucagon synthesizing α (alpha)-cells. Inhibition of IHoP by siRNA resulted in the loss of glucagon expression, which induced low blood glucose levels (63–85 mg/dL). Subsequently, cellular apoptosis was observed throughout the islet, including the insulin-producing β (beta)-cells. Islets of pre-onset diabetic patients showed normal expression of IHoP and glucagon; however IHoP was lost upon onset of the disease. Conclusion These data suggest that IHoP could be a new functional protein in the islet, and may play a role in islet homeostasis. PMID:22143342

  1. An optical method to evaluate both mass and functional competence of pancreatic α- and β-cells.

    PubMed

    Wang, Yi; Han, Chengsheng; Zhu, Wenzhen; Wu, Zhengxing; Liu, Yanmei; Chen, Liangyi

    2016-06-15

    Imbalanced glucagon and insulin release leads to the onset of type 2 diabetes. To pinpoint the underlying primary driving force, here we have developed a fast, non-biased optical method to measure ratios of pancreatic α- and β-cell mass and function simultaneously. We firstly label both primary α- and β-cells with the red fluorescent probe ZinRhodaLactam-1 (ZRL1), and then highlight α-cells by selectively quenching the ZRL1 signal from β-cells. Based on the signals before and after quenching, we calculate the ratio of the α-cell to β-cell mass within live islets, which we found matched the results from immunohistochemistry. From the same islets, glucagon and insulin release capability can be concomitantly measured. Thus, we were able to measure the ratio of α-cell to β-cell mass and their function in wild-type and diabetic Lepr(db)/Lepr(db) (denoted db/db) mice at different ages. We find that the initial glucose intolerance that appears in 10-week-old db/db mice is associated with further expansion of α-cell mass prior to deterioration in functional β-cell mass. Our method is extendable to studies of islet mass and function in other type 2 diabetes animal models, which shall benefit mechanistic studies of imbalanced hormone secretion during type 2 diabetes progression. PMID:27173492

  2. The angiotensin-converting enzyme 2/angiotensin (1-7)/Mas axis protects the function of pancreatic β cells by improving the function of islet microvascular endothelial cells.

    PubMed

    Lu, Chun-Li; Wang, Ying; Yuan, Li; Li, Yang; Li, Xiao-Ya

    2014-11-01

    In the diabetic state, the local rennin-angiotensin system (RAS) is activated in the pancreas, and is strongly associated with islet dysfunction. The angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7) [Ang(1-7)]/Mas axis is a protective, negative regulator of the classical renin-angiotensin system. In this study, we assessed the role of the ACE2/Ang(1‑7)/Mas axis in pancreatic β cell survival and function. ACE2 knockout and wild-type mice were fed a high-fat diet for 16 weeks. We then performed terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, and determined the expression levels of interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in the pancreatic islets. The effects of Ang(1-7) or Mas receptor silencing on endothelial function were assessed in MS-1 cells. MIN6 cells were then co-cultured with the MS-1 cells to evaluate the effects of ACE2 on insulin secretion. The ACE2 knockout mice were more susceptible than the wild-type mice to high-fat diet-induced β cell dysfunction. The TUNEL-positive area of the pancreatic islets and the expression levels of IL-1β and iNOS were markedly increased in the ACE2 knockout mice compared with their wild-type littermates. The Mas-silenced MS-1 cells were more sensitive to palmitate-induced dysfunction and apoptosis in vitro. Ang(1-7) increased the activity of the Akt/endothelial NOS/nitric oxide (NO) pathway in the MS-1 cells, protected MIN6 cells against palmitate-induced apoptosis, and improved MIN6 insulin secretory function in the co-culture system. In conclusion, this study demonstrates that the ACE2/Ang(1-7)/Mas axis is a potential target for protecting the funcion of β cells by improving the function of islet microvascular endothelial cells. PMID:25175177

  3. Functional Analysis of Novel Candidate Regulators of Insulin Secretion in the MIN6 Mouse Pancreatic β Cell Line.

    PubMed

    Kobayashi, Masaki; Yamato, Eiji; Tanabe, Koji; Tashiro, Fumi; Miyazaki, Satsuki; Miyazaki, Jun-ichi

    2016-01-01

    Elucidating the regulation of glucose-stimulated insulin secretion (GSIS) in pancreatic β cells is important for understanding and treating diabetes. The pancreatic β cell line, MIN6, retains GSIS but gradually loses it in long-term culture. The MIN6 subclone, MIN6c4, exhibits well-regulated GSIS even after prolonged culture. We previously used DNA microarray analysis to compare gene expression in the parental MIN6 cells and MIN6c4 cells and identified several differentially regulated genes that may be involved in maintaining GSIS. Here we investigated the potential roles of six of these genes in GSIS: Tmem59l (Transmembrane protein 59 like), Scgn (Secretagogin), Gucy2c (Guanylate cyclase 2c), Slc29a4 (Solute carrier family 29, member 4), Cdhr1 (Cadherin-related family member 1), and Celsr2 (Cadherin EGF LAG seven-pass G-type receptor 2). These genes were knocked down in MIN6c4 cells using lentivirus vectors expressing gene-specific short hairpin RNAs (shRNAs), and the effects of the knockdown on insulin expression and secretion were analyzed. Suppression of Tmem59l, Scgn, and Gucy2c expression resulted in significantly decreased glucose- and/or KCl-stimulated insulin secretion from MIN6c4 cells, while the suppression of Slc29a4 expression resulted in increased insulin secretion. Tmem59l overexpression rescued the phenotype of the Tmem59l knockdown MIN6c4 cells, and immunostaining analysis indicated that the TMEM59L protein colocalized with insulin and GM130, a Golgi complex marker, in MIN6 cells. Collectively, our findings suggested that the proteins encoded by Tmem59l, Scgn, Gucy2c, and Slc29a4 play important roles in regulating GSIS. Detailed studies of these proteins and their functions are expected to provide new insights into the molecular mechanisms involved in insulin secretion. PMID:26986842

  4. Functional Analysis of Novel Candidate Regulators of Insulin Secretion in the MIN6 Mouse Pancreatic β Cell Line

    PubMed Central

    Kobayashi, Masaki; Yamato, Eiji; Tanabe, Koji; Tashiro, Fumi; Miyazaki, Satsuki; Miyazaki, Jun-ichi

    2016-01-01

    Elucidating the regulation of glucose-stimulated insulin secretion (GSIS) in pancreatic β cells is important for understanding and treating diabetes. The pancreatic β cell line, MIN6, retains GSIS but gradually loses it in long-term culture. The MIN6 subclone, MIN6c4, exhibits well-regulated GSIS even after prolonged culture. We previously used DNA microarray analysis to compare gene expression in the parental MIN6 cells and MIN6c4 cells and identified several differentially regulated genes that may be involved in maintaining GSIS. Here we investigated the potential roles of six of these genes in GSIS: Tmem59l (Transmembrane protein 59 like), Scgn (Secretagogin), Gucy2c (Guanylate cyclase 2c), Slc29a4 (Solute carrier family 29, member 4), Cdhr1 (Cadherin-related family member 1), and Celsr2 (Cadherin EGF LAG seven-pass G-type receptor 2). These genes were knocked down in MIN6c4 cells using lentivirus vectors expressing gene-specific short hairpin RNAs (shRNAs), and the effects of the knockdown on insulin expression and secretion were analyzed. Suppression of Tmem59l, Scgn, and Gucy2c expression resulted in significantly decreased glucose- and/or KCl-stimulated insulin secretion from MIN6c4 cells, while the suppression of Slc29a4 expression resulted in increased insulin secretion. Tmem59l overexpression rescued the phenotype of the Tmem59l knockdown MIN6c4 cells, and immunostaining analysis indicated that the TMEM59L protein colocalized with insulin and GM130, a Golgi complex marker, in MIN6 cells. Collectively, our findings suggested that the proteins encoded by Tmem59l, Scgn, Gucy2c, and Slc29a4 play important roles in regulating GSIS. Detailed studies of these proteins and their functions are expected to provide new insights into the molecular mechanisms involved in insulin secretion. PMID:26986842

  5. [New model of acute pancreatitis].

    PubMed

    Cherkezova-Kinova, E; Lateva, E

    1981-01-01

    The authors propose a new model of acute pancreatitis by infusing duodenal content, obtained both from animals with experimental pancreatitis and from patients with pancreatitis, hepatitis and cholecystitis, into the duodenum of experimental animals without pressure for a period of several days. Pancreatitis was established functionally and histomorphologically. The control group of animals did not reveal deviations from the norm after infusion of duodenal content. The authors suggested the presence of pathogenic substances in the duodenal content of animals and sick persons, and these components damaged the pancreas, liver and kidneys by means of blood and lymph ways. PMID:7227280

  6. An automated system for pulmonary function testing

    NASA Technical Reports Server (NTRS)

    Mauldin, D. G.

    1974-01-01

    An experiment to quantitate pulmonary function was accepted for the space shuttle concept verification test. The single breath maneuver and the nitrogen washout are combined to reduce the test time. Parameters are defined from the forced vital capacity maneuvers. A spirometer measures the breath volume and a magnetic section mass spectrometer provides definition of gas composition. Mass spectrometer and spirometer data are analyzed by a PDP-81 digital computer.

  7. Chronic pancreatitis.

    PubMed

    Majumder, Shounak; Chari, Suresh T

    2016-05-01

    Chronic pancreatitis describes a wide spectrum of fibro-inflammatory disorders of the exocrine pancreas that includes calcifying, obstructive, and steroid-responsive forms. Use of the term chronic pancreatitis without qualification generally refers to calcifying chronic pancreatitis. Epidemiology is poorly defined, but incidence worldwide seems to be on the rise. Smoking, drinking alcohol, and genetic predisposition are the major risk factors for chronic calcifying pancreatitis. In this Seminar, we discuss the clinical features, diagnosis, and management of chronic calcifying pancreatitis, focusing on pain management, the role of endoscopic and surgical intervention, and the use of pancreatic enzyme-replacement therapy. Management of patients is often challenging and necessitates a multidisciplinary approach. PMID:26948434

  8. Track/train dynamics test report transfer function test. Volume 1: Test

    NASA Technical Reports Server (NTRS)

    Vigil, R. A.

    1975-01-01

    A description is presented of the transfer function test performed on an open hopper freight car loaded with 80 tons of coal. Test data and a post-test update of the requirements document and test procedure are presented. Included are a statement of the test objective, a description of the test configurations, test facilities, test methods, data acquisition/reduction operations, and a chronological test summary. An index to the data for the three test configurations (X, Y, and Z-axis tests) is presented along with test sequence, run number, test reference, and input parameters.

  9. In Vivo Functional Platform Targeting Patient-Derived Xenografts Identifies WDR5-Myc Association as a Critical Determinant of Pancreatic Cancer.

    PubMed

    Carugo, Alessandro; Genovese, Giannicola; Seth, Sahil; Nezi, Luigi; Rose, Johnathon Lynn; Bossi, Daniela; Cicalese, Angelo; Shah, Parantu Krushnakant; Viale, Andrea; Pettazzoni, Piergiorgio Francesco; Akdemir, Kadir Caner; Bristow, Christopher Aaron; Robinson, Frederick Scott; Tepper, James; Sanchez, Nora; Gupta, Sonal; Estecio, Marcos Roberto; Giuliani, Virginia; Dellino, Gaetano Ivan; Riva, Laura; Yao, Wantong; Di Francesco, Maria Emilia; Green, Tessa; D'Alesio, Carolina; Corti, Denise; Kang, Ya'an; Jones, Philip; Wang, Huamin; Fleming, Jason Bates; Maitra, Anirban; Pelicci, Pier Giuseppe; Chin, Lynda; DePinho, Ronald Anthony; Lanfrancone, Luisa; Heffernan, Timothy Paul; Draetta, Giulio Francesco

    2016-06-28

    Current treatment regimens for pancreatic ductal adenocarcinoma (PDAC) yield poor 5-year survival, emphasizing the critical need to identify druggable targets essential for PDAC maintenance. We developed an unbiased and in vivo target discovery approach to identify molecular vulnerabilities in low-passage and patient-derived PDAC xenografts or genetically engineered mouse model-derived allografts. Focusing on epigenetic regulators, we identified WDR5, a core member of the COMPASS histone H3 Lys4 (H3K4) MLL (1-4) methyltransferase complex, as a top tumor maintenance hit required across multiple human and mouse tumors. Mechanistically, WDR5 functions to sustain proper execution of DNA replication in PDAC cells, as previously suggested by replication stress studies involving MLL1, and c-Myc, also found to interact with WDR5. We indeed demonstrate that interaction with c-Myc is critical for this function. By showing that ATR inhibition mimicked the effects of WDR5 suppression, these data provide rationale to test ATR and WDR5 inhibitors for activity in this disease. PMID:27320920

  10. Identification of fucosylated haptoglobin as a novel tumor marker for pancreatic cancer and its possible application for a clinical diagnostic test.

    PubMed

    Miyoshi, Eiji; Shinzaki, Shinichiro; Moriwaki, Kenta; Matsumoto, Hitoshi

    2010-01-01

    Fucosylation is one of the most important oligosaccharide modifications in cancer and inflammation. The fucosylation level is increased in total cellular proteins of cancer cells as well as in sera of patients with cancer. Recently, on AAL blot analysis, we found a fucosylated glycoprotein of 40 kDa in sera of patients with pancreatic cancer. Based on its N-terminal sequence, this protein was identified as haptoglobin. Fucosylated haptoglobin was increased in sera of patients with several kinds of cancer and the positive rate was higher in pancreatic cancer. The level of fucosylated haptoglobin was not correlated with total haptoglobin, suggesting that a factor other than inflammation could regulate the production of fucosylated haptoglobin. Mass spectrometry analysis revealed the detailed oligosaccharide structure of fucosylated haptoglobin purified from sera of patients with pancreatic cancer. For clinical applications, we developed a lectin-antibody ELISA system for quantifying fucosylated haptoglobin. In this review, we would like to summarize the history of the identification of fucosylated haptoglobin as a marker for pancreatic cancer and its possible application for a clinical diagnostic test. PMID:20816478

  11. Gas Test Loop Functional and Technical Requirements

    SciTech Connect

    Glen R. Longhurst; Soli T. Khericha; James L. Jones

    2004-09-01

    This document defines the technical and functional requirements for a gas test loop (GTL) to be constructed for the purpose of providing a high intensity fast-flux irradiation environment for developers of advanced concept nuclear reactors. This capability is needed to meet fuels and materials testing requirements of the designers of Generation IV (GEN IV) reactors and other programs within the purview of the Advanced Fuel Cycle Initiative (AFCI). Space nuclear power development programs may also benefit by the services the GTL will offer. The overall GTL technical objective is to provide developers with the means for investigating and qualifying fuels and materials needed for advanced reactor concepts. The testing environment includes a fast-flux neutron spectrum of sufficient intensity to perform accelerated irradiation testing. Appropriate irradiation temperature, gaseous environment, test volume, diagnostics, and access and handling features are also needed. This document serves to identify those requirements as well as generic requirements applicable to any system of this kind.

  12. Variability of routine pulmonary function tests.

    PubMed Central

    Hruby, J; Butler, J

    1975-01-01

    Pulmonary function tests sometimes indicate a progressive deterioration and at other times a 'stepwise' worsening which may be followed by improvement. Interpretation depends on the extent of random or diurnal variations in function. Routing pulmonary function tests (VC, FEV1, FRC, and airway resistance (Raw)) were repeatedly measured in normal subjects, patients with stable irreversible airways obstruction, and patients with stable restrictive disease. In all groups there was a significant (P less than 0.001) diurnal variation in Raw, with high values in the morning, low values at noon, and rising values in the evening. The midday Raw values were about 80% of the highest daily values. The considerable random and diurnal variability seen in all tests is reflected in the range of high and low values (% of mean individual response) in individuals. The largest variation in an individual between measurements taken at two different times was 81% in Raw (range: 40% above to 41% below the mean). There was less variation in FEV1 (29%), FRC (62%), and VC (30%). Thus the finding of a stepwise change in function could reflect its natrual variability. When repeated studies are done to assess progress or the effects of therapy on disease, there are many factors, including the time of day at which the tests are performed, which should be standardized as far as possible. PMID:1198395

  13. Inhibition of Porcine Pancreatic Amylase Activity by Sulfamethoxazole: Structural and Functional Aspect.

    PubMed

    Maity, Sujan; Mukherjee, Koel; Banerjee, Amrita; Mukherjee, Suman; Dasgupta, Dipak; Gupta, Suvroma

    2016-06-01

    Combating Type-2 diabetes mellitus is a pivotal challenge in front of the present world. Several lines of therapy are in practice for resisting this deadly disease which often culminates with cardiovascular complexities, neuropathy and retinopathy. Among various therapies, administration of alpha glucosidase inhibitors is common and widely practiced. Sulfonylurea category of anti diabetic drug often suffers from cross reactivity with sulfamethoxazole (SMX), a common drug in use to treat a handful of microbial infections. However the specific cellular target generating postprandial hypoglycemia on SMX administration is till date unraveled. The present work has been initiated to elucidate the effects of a group of sulfonamide drugs inclusive of SMX for their amylase inhibitory role. SMX inhibits porcine pancreatic amylase (PPA) in a noncompetitive mode with an average IC50 value 0.94 mM respectively. Interaction of SMX with PPA is manifested with gradual quenching of tryptophan fluorescence with concomitant shift in lambda max value (λmax). Binding is governed by entropy driven factor (24.8 cal mol(-1) K(-1)) with unfavorable contribution from enthalpy change. SMX interferes with the activity of acarbose in a synergistic mode to reduce the effective dose of acarbose as evident from the in vitro PPA inhibition study. In summary, loss of PPA activity in presence of SMX is indicative of structural changes of PPA which is further augmented in the presence of acarbose as explained in the schematic model and docking study. PMID:27272220

  14. Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer.

    PubMed

    Li, Min; Wang, Xiaochi; Li, Wei; Li, Fei; Yang, Hui; Wang, Hao; Brunicardi, F Charles; Chen, Changyi; Yao, Qizhi; Fisher, William E

    2008-11-01

    Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer. PMID:18823376

  15. Somatostatin Receptor-1 Induces Cell Cycle Arrest and Inhibits Tumor Growth in Pancreatic Cancer

    PubMed Central

    Li, Min; Wang, Xiaochi; Li, Wei; Li, Fei; Yang, Hui; Wang, Hao; Brunicardi, F. Charles; Chen, Changyi; Yao, Qizhi; Fisher, William E.

    2010-01-01

    Functional somatostatin receptors (SSTRs) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G0/G1 growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n=5, p<0.05, t-test), and inhibited tumor weight by 69% and 47%, (n=5, p<0.05, t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer. PMID:18823376

  16. Diagnosis of pancreatitis in dogs and cats.

    PubMed

    Xenoulis, P G

    2015-01-01

    Pancreatitis is the most common disorder of the exocrine pancreas in both dogs and cats. Ante-mortem diagnosis of canine and feline pancreatitis can be challenging. The clinical picture of dogs and cats with pancreatitis varies greatly (from very mild to severe or even fatal) and is characterised by non-specific findings. Complete blood count, serum biochemistry profile and urinalysis should always be performed in dogs and cats suspected of having pancreatitis, although findings are not-specific for pancreatitis. Serum amylase and lipase activities and trypsin-like immunoreactivity (TLI) concentrations have no or only limited clinical value for the diagnosis of pancreatitis in either dogs or cats. Conversely, serum pancreatic lipase immunoreactivity (PLI) concentration is currently considered to be the clinicopathological test of choice for the diagnosis of canine and feline pancreatitis. Abdominal radiography is a useful diagnostic tool for the exclusion of other diseases that may cause similar clinical signs to those of pancreatitis. Abdominal ultrasonography can be very useful for the diagnosis of pancreatitis, but this depends largely on the clinician's experience. Histopathological examination of the pancreas is considered the gold standard for the diagnosis and classification of pancreatitis, but it is not without limitations. In clinical practice, a combination of careful evaluation of the animal's history, serum PLI concentration and abdominal ultrasonography, together with pancreatic cytology or histopathology when indicated or possible, is considered to be the most practical and reliable means for an accurate diagnosis or exclusion of pancreatitis compared with other diagnostic modalities. PMID:25586803

  17. Platelet function tests: a comparative review

    PubMed Central

    Paniccia, Rita; Priora, Raffaella; Alessandrello Liotta, Agatina; Abbate, Rosanna

    2015-01-01

    In physiological hemostasis a prompt recruitment of platelets on the vessel damage prevents the bleeding by the rapid formation of a platelet plug. Qualitative and/or quantitative platelet defects promote bleeding, whereas the high residual reactivity of platelets in patients on antiplatelet therapies moves forward thromboembolic complications. The biochemical mechanisms of the different phases of platelet activation – adhesion, shape change, release reaction, and aggregation – have been well delineated, whereas their complete translation into laboratory assays has not been so fulfilled. Laboratory tests of platelet function, such as bleeding time, light transmission platelet aggregation, lumiaggregometry, impedance aggregometry on whole blood, and platelet activation investigated by flow cytometry, are traditionally utilized for diagnosing hemostatic disorders and managing patients with platelet and hemostatic defects, but their use is still limited to specialized laboratories. To date, a point-of-care testing (POCT) dedicated to platelet function, using pertinent devices much simpler to use, has now become available (ie, PFA-100, VerifyNow System, Multiplate Electrode Aggregometry [MEA]). POCT includes new methodologies which may be used in critical clinical settings and also in general laboratories because they are rapid and easy to use, employing whole blood without the necessity of sample processing. Actually, these different platelet methodologies for the evaluation of inherited and acquired bleeding disorders and/or for monitoring antiplatelet therapies are spreading and the study of platelet function is strengthening. In this review, well-tried and innovative platelet function tests and their methodological features and clinical applications are considered. PMID:25733843

  18. Early detection of pancreatic cancer

    PubMed Central

    Ahuja, Nita

    2015-01-01

    Pancreatic adenocarcinoma is a low-incident but highly mortal disease. It accounts for only 3% of estimated new cancer cases each year but is currently the fourth common cause of cancer mortality. By 2030, it is expected to be the 2nd leading cause of cancer death. There is a clear need to diagnose and classify pancreatic cancer at earlier stages in order to give patients the best chance at a definitive cure through surgery. Three precursor lesions that distinctly lead to pancreatic adenocarcinoma have been identified, and we have increasing understanding the non-genetic and genetic risk factors for the disease. With increased understanding about the risk factors, the familial patters, and associated accumulation of genetic mutations involved in pancreatic cancer, we know that there are mutations that occur early in the development of pancreatic cancer and that improved genetic risk-based strategies in screening for pancreatic cancer may be possible and successful at saving or prolonging lives. The remaining challenge is that current standards for diagnosing pancreatic cancer remain too invasive and too costly for widespread screening for pancreatic cancer. Furthermore, the promises of noninvasive methods of detection such as blood, saliva, and stool remain underdeveloped or lack robust testing. However, significant progress has been made, and we are drawing closer to a strategy for the screening and early detection of pancreatic cancer. PMID:26361402

  19. Exocrine pancreatic insufficiency in a yellow-naped Amazon (Amazona ochrocephala) with pancreatic adenocarcinoma.

    PubMed

    Ritchey, J W; Degernes, L A; Brown, T T

    1997-01-01

    This report describes exocrine pancreatic insufficiency in a yellow-naped Amazon (Amazona ochrocephala) with complete effacement of the pancreas by a pancreatic adenocarcinoma. The bird presented with a 3-month history of weight loss and voluminous, foul-smelling droppings. Clinically, routine hematologic findings were normal and fecal tests were performed to evaluate exocrine pancreatic function. The fecal function tests were positive for neutral and split fats and negative for trypsin. Oral administration of corn oil did not result in elevation of blood triglyceride levels. Two days later, the triglyceride tolerance test was repeated using corn oil mixed with pancreatic enzymes. This time, there was a 70% elevation of blood triglyceride levels. Because of a poor prognosis, the bird was euthanatized. At necropsy, the pancreas was diffusely enlarged, white, nodular, and firm. The liver contained multiple, 1-2-mm-diameter, randomly located, tan nodules. Microscopically, the pancreas was effaced by numerous lobules of neoplastic ductular structures surrounded by abundant fibrous connective tissue. In the liver, the hepatic parenchyma was replaced by multiple, well-demarcated, nonencapsulated foci of neoplastic tissue similar to that in the pancreas. PMID:9150549

  20. [Hereditary pancreatitis].

    PubMed

    Dyrla, Przemysław; Nowak, Tomasz; Gil, Jerzy; Adamiec, Cezary; Bobula, Mariusz; Saracyn, Marek

    2016-02-01

    Hereditary pancreatitis (HP) is a rare, heterogeneous familial disease and should be suspected in any patient who has suffered at least two attacks of acute pancreatitis for which there is no underlying cause and unexplained chronic pancreatitis with a family history in a first- or second degree relative. with an early onset, mostly during childhood. Genetic factors have been implied in cases of familial chronic pancreatitis. The most common are mutations of the PRSS1 gene on the long arm of the chromosome 7, encoding for the cationic trypsinogen. The inheritance pattern is autosomal dominant with an incomplete penetrance (80%). The inflammation results in repeated DNA damage, error-prone repair mechanisms and the progressive accumulation of genetic mutations. Risk of pancreatic adenocarcinoma is a major concern of many patients with hereditary chronic pancreatitis, but the individual risk is poorly defined. Better risk models of pancreatic cancer in individual patients based on etiology of pancreatitis, family history, genetics, smoking, alcohol, diabetes and the patient's age are needed. PMID:27000817

  1. Pancreatic cancer

    PubMed Central

    Vincent, Audrey; Herman, Joseph; Schulick, Rich; Hruban, Ralph H; Goggins, Michael

    2011-01-01

    Substantial progress has been made in our understanding of the biology of pancreatic cancer, and advances in patients’ management have also taken place. Evidence is beginning to show that screening first-degree relatives of individuals with several family members affected by pancreatic cancer can identify non-invasive precursors of this malignant disease. The incidence of and number of deaths caused by pancreatic tumours have been gradually rising, even as incidence and mortality of other common cancers have been declining. Despite developments in detection and management of pancreatic cancer, only about 4% of patients will live 5 years after diagnosis. Survival is better for those with malignant disease localised to the pancreas, because surgical resection at present offers the only chance of cure. Unfortunately, 80–85% of patients present with advanced unresectable disease. Furthermore, pancreatic cancer responds poorly to most chemotherapeutic agents. Hence, we need to understand the biological mechanisms that contribute to development and progression of pancreatic tumours. In this Seminar we will discuss the most common and deadly form of pancreatic cancer, pancreatic ductal adenocarcinoma. PMID:21620466

  2. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  3. Pancreatic Tuberculosis.

    PubMed

    Chaudhary, Poras; Bhadana, Utsav; Arora, Mohinder P

    2015-12-01

    Tuberculosis of the pancreas is extremely rare and in most of the cases mimics pancreatic carcinoma. There are a number of case reports on pancreatic tuberculosis with various different presentations, but only a few case series have been published, and most of our knowledge about this disease comes from individual case reports. Patients of pancreatic tuberculosis may remain asymptomatic initially and manifest as an abscess or a mass involving local lymph nodes and usually present with non-specific features. Pancreatic tuberculosis may present with a wide range of imaging findings. It is difficult to diagnose tuberculosis of pancreas on imaging studies as they may present with masses, cystic lesions or abscesses and mass lesions in most of the cases mimic pancreatic carcinoma. As it is a rare entity, it cannot be recommended but suggested that pancreatic tuberculosis should be considered in cases with a large space occupying lesions associated with necrotic peripancreatic lymph nodes and constitutional symptoms. Ultrasonography/computed tomography/endosonography-guided biopsy is the recommended diagnostic technique. Most patients achieve complete cure with standard antituberculous therapy. The aims of this study are to review clinical presentation, diagnostic studies, and management of pancreatic tuberculosis and to present our experience of 5 cases of pancreatic tuberculosis. PMID:26884661

  4. Mutations in SLC2A2 Gene Reveal hGLUT2 Function in Pancreatic β Cell Development*

    PubMed Central

    Michau, Aurélien; Guillemain, Ghislaine; Grosfeld, Alexandra; Vuillaumier-Barrot, Sandrine; Grand, Teddy; Keck, Mathilde; L'Hoste, Sébastien; Chateau, Danielle; Serradas, Patricia; Teulon, Jacques; De Lonlay, Pascale; Scharfmann, Raphaël; Brot-Laroche, Edith; Leturque, Armelle; Le Gall, Maude

    2013-01-01

    The structure-function relationships of sugar transporter-receptor hGLUT2 coded by SLC2A2 and their impact on insulin secretion and β cell differentiation were investigated through the detailed characterization of a panel of mutations along the protein. We studied naturally occurring SLC2A2 variants or mutants: two single-nucleotide polymorphisms and four proposed inactivating mutations associated to Fanconi-Bickel syndrome. We also engineered mutations based on sequence alignment and conserved amino acids in selected domains. The single-nucleotide polymorphisms P68L and T110I did not impact on sugar transport as assayed in Xenopus oocytes. All the Fanconi-Bickel syndrome-associated mutations invalidated glucose transport by hGLUT2 either through absence of protein at the plasma membrane (G20D and S242R) or through loss of transport capacity despite membrane targeting (P417L and W444R), pointing out crucial amino acids for hGLUT2 transport function. In contrast, engineered mutants were located at the plasma membrane and able to transport sugar, albeit with modified kinetic parameters. Notably, these mutations resulted in gain of function. G20S and L368P mutations increased insulin secretion in the absence of glucose. In addition, these mutants increased insulin-positive cell differentiation when expressed in cultured rat embryonic pancreas. F295Y mutation induced β cell differentiation even in the absence of glucose, suggesting that mutated GLUT2, as a sugar receptor, triggers a signaling pathway independently of glucose transport and metabolism. Our results describe the first gain of function mutations for hGLUT2, revealing the importance of its receptor versus transporter function in pancreatic β cell development and insulin secretion. PMID:23986439

  5. Pancreatic injury.

    PubMed

    Ahmed, Nasim; Vernick, Jerome J

    2009-12-01

    Injury to the pancreas, because of its retroperitoneal location, is a rare occurrence, most commonly seen with penetrating injuries (gun shot or stab wounds). Blunt trauma to the pancreas accounts for only 25% of the cases. Pancreatic injuries are associated with high morbidity and mortality due to accompanying vascular and duodenal injuries. Pancreatic injuries are not always easy to diagnose resulting in life threatening complications. Physical examination as well as serum amylase is not diagnostic following blunt trauma. Computed tomography (CT) scan can delineate the injury or transaction of the pancreas. Endoscopic retrograde pancreaticography (ERCP) is the main diagnostic modality for evaluation of the main pancreatic duct. Unrecognized ductal injury leads to pancreatic pseudocyst, fistula, abscess, and other complications. Management depends upon the severity of the pancreatic injury as well as associated injuries. Damage control surgery in hemodynamic unstable patients reduces morbidity and mortality. PMID:20016434

  6. Prediction of protein conformation on the basis of a search for compact structures: test on avian pancreatic polypeptide.

    PubMed Central

    Liwo, A.; Pincus, M. R.; Wawak, R. J.; Rackovsky, S.; Scheraga, H. A.

    1993-01-01

    Based on the concept that hydrophobic interactions cause a polypeptide chain to adopt a compact structure, a method is proposed to predict the structure of a protein. The procedure is carried out in four stages: (1) use of a virtual-bond united-residue approximation with the side chains represented by spheres to search conformational space extensively using specially designed interactions to lead to a collapsed structure, (2) conversion of the lowest-energy virtual-bond united-residue chain to one with a real polypeptide backbone, with optimization of the hydrogen-bond network among the backbone groups, (3) perturbation of the latter structure by the electrostatically driven Monte Carlo (EDMC) procedure, and (4) conversion of the spherical representation of the side chains to real groups and perturbation of the whole molecule by the EDMC procedure using the empirical conformational energy program for peptides (ECEPP/2) energy function plus hydration. Application of this procedure to the 36-residue avian pancreatic polypeptide led to a structure that resembled the one determined by X-ray crystallography; it had an alpha-helix starting at residue 13, with the N-terminal portion of the chain in an extended conformation packed against the alpha-helix. Similar structures with slightly higher energies, but looser packing, were also obtained. PMID:8251944

  7. Platelet Function Tests in Bleeding Disorders.

    PubMed

    Lassila, Riitta

    2016-04-01

    Functional disorders of platelets can involve any aspect of platelet physiology, with many different effects or outcomes. These include platelet numbers (thrombocytosis or thrombocytopenia); changes in platelet production or destruction, or capture to the liver (Ashwell receptor); altered adhesion to vascular injury sites and/or influence on hemostasis and wound healing; and altered activation or receptor functions, shape change, spreading and release reactions, procoagulant and antifibrinolytic activity. Procoagulant membrane alterations, and generation of thrombin and fibrin, also affect platelet aggregation. The above parameters can all be studied, but standardization and quality control of assay methods have been limited despite several efforts. Only after a comprehensive clinical bleeding assessment, including family history, information on drug use affecting platelets, and exclusion of coagulation factor, and tissue deficits, should platelet function testing be undertaken to confirm an abnormality. Current diagnostic tools include blood cell counts, platelet characteristics according to the cell counter parameters, peripheral blood smear, exclusion of pseudothrombocytopenia, whole blood aggregometry (WBA) or light transmission aggregometry (LTA) in platelet-rich plasma, luminescence, platelet function analysis (PFA-100) for platelet adhesion and deposition to collagen cartridges under blood flow, and finally transmission electron microscopy to exclude rare structural defects leading to functional deficits. The most validated test panels are included in WBA, LTA, and PFA. Because platelets are isolated from their natural environment, many simplifications occur, as circulating blood and interaction with vascular wall are omitted in these assays. The target to reach a highly specific platelet disorder diagnosis in routine clinical management can be exhaustive, unless needed for genetic counseling. The elective overall assessment of platelet function disorder

  8. Endoscopic sphincterotomy in patients with stenosis of ampulla of Vater: Three-year follow-up of exocrine pancreatic function and clinical symptoms

    PubMed Central

    Ewald, Nils; Marzeion, Axel Michael; Bretzel, Reinhard Georg; Kloer, Hans Ulrich; Hardt, Philip Daniel

    2007-01-01

    AIM: To investigate retrospectively the long-term effect of endoscopic sphincterotomy (ES) including exocrine pancreatic function in patients with stenosis of ampulla of Vater. METHODS: After diagnostic endoscopic retrograde cholangiopancreatography (ERCP) and ES because of stenosis of the ampulla of Vater (SOD Type I), follow-up examinations were performed in 60 patients (mean follow-up time 37.7 mo). Patients were asked about clinical signs and symptoms at present and before intervention using a standard questionnaire. Before and after ES exocrine pancreatic function was assessed by determination of immunoreactive fecal elastase 1. Serum enzymes indicating cholestasis as well as serum lipase and amylase were measured. RESULTS: Eighty percent of patients reported an improvement in their general condition after ES. The fecal elastase 1 concentrations (FEC) in all patients increased significantly after ES. This effect was even more marked in patients with pathologically low concentrations (< 200 μg/g) of fecal elastase prior to ES. The levels of serum lipase and amylase as well as serum alcaline phosphatase (AP) and gamma-glutamyltranspeptidase (GGT) decreased significantly after ES. CONCLUSION: The results of this study demonstrate that patients with stenosis of the ampulla of Vater can be successfully treated with endoscopic sphincterotomy. The positive effect is not only indicated by sustained improvement of clinical symptoms and cholestasis but also by improvement of exocrine pancreatic function. PMID:17352020

  9. Potential for dose-escalation and reduction of risk in pancreatic cancer using IMRT optimization with lexicographic ordering and gEUD-based cost functions.

    PubMed

    Spalding, Aaron C; Jee, Kyung-Wook; Vineberg, Karen; Jablonowski, Marla; Fraass, Benedick A; Pan, Charlie C; Lawrence, Theodore S; Haken, Randall K Ten; Ben-Josef, Edgar

    2007-02-01

    Radiotherapy for pancreatic cancer is limited by the tolerance of local organs at risk (OARs) and frequent overlap of the planning target volume (PTV) and OAR volumes. Using lexicographic ordering (LO), a hierarchical optimization technique, with generalized equivalent uniform dose (gEUD) cost functions, we studied the potential of intensity modulated radiation therapy (IMRT) to increase the dose to pancreatic tumors and to areas of vascular involvement that preclude surgical resection [surgical boost volume (SBV)]. We compared 15 forward planned three-dimensional conformal (3DCRT) and IMRT treatment plans for locally advanced unresectable pancreatic cancer. We created IMRT plans optimized using LO with gEUD-based cost functions that account for the contribution of each part of the resulting inhomogeneous dose distribution. LO-IMRT plans allowed substantial PTV dose escalation compared with 3DCRT; median increase from 52 Gy to 66 Gy (a=-5,p<0.005) and median increase from 50 Gy to 59 Gy (a=-15,p<0.005). LO-IMRT also allowed increases to 85 Gy in the SBV, regardless of a value, along with significant dose reductions in OARs. We conclude that LO-IMRT with gEUD cost functions could allow dose escalation in pancreas tumors with concomitant reduction in doses to organs at risk as compared with traditional 3DCRT. PMID:17388169

  10. Potential for dose-escalation and reduction of risk in pancreatic cancer using IMRT optimization with lexicographic ordering and gEUD-based cost functions

    SciTech Connect

    Spalding, Aaron C.; Jee, Kyung-Wook; Vineberg, Karen; Jablonowski, Marla; Fraass, Benedick A.; Pan, Charlie C.; Lawrence, Theodore S.; Ten Haken, Randall K.; Ben-Josef, Edgar

    2007-02-15

    Radiotherapy for pancreatic cancer is limited by the tolerance of local organs at risk (OARs) and frequent overlap of the planning target volume (PTV) and OAR volumes. Using lexicographic ordering (LO), a hierarchical optimization technique, with generalized equivalent uniform dose (gEUD) cost functions, we studied the potential of intensity modulated radiation therapy (IMRT) to increase the dose to pancreatic tumors and to areas of vascular involvement that preclude surgical resection [surgical boost volume (SBV)]. We compared 15 forward planned three-dimensional conformal (3DCRT) and IMRT treatment plans for locally advanced unresectable pancreatic cancer. We created IMRT plans optimized using LO with gEUD-based cost functions that account for the contribution of each part of the resulting inhomogeneous dose distribution. LO-IMRT plans allowed substantial PTV dose escalation compared with 3DCRT; median increase from 52 Gy to 66 Gy (a=-5,p<0.005) and median increase from 50 Gy to 59 Gy (a=-15,p<0.005). LO-IMRT also allowed increases to 85 Gy in the SBV, regardless of a value, along with significant dose reductions in OARs. We conclude that LO-IMRT with gEUD cost functions could allow dose escalation in pancreas tumors with concomitant reduction in doses to organs at risk as compared with traditional 3DCRT.

  11. Stevioside counteracts the glyburide-induced desensitization of the pancreatic beta-cell function in mice: studies in vitro.

    PubMed

    Chen, Jianguo; Jeppesen, Per Bendix; Nordentoft, Iver; Hermansen, Kjeld

    2006-12-01

    The sulfonylurea glyburide (GB) is one of the most frequently used drugs in diabetes treatment. Long-term pretreatment with GB causes elevated basal insulin secretion (BIS) and decreased glucose-stimulated insulin secretion (GSIS). These characteristics may play an important role for the development of hypoglycemia and secondary failure. Stevioside (SVS), a substance extracted from leaves of Stevia rebaudiana Bertoni, enhances GSIS but not BIS. The aim of the present study was to clarify whether 24-hour exposure of isolated mouse islets to GB causes dose-dependent decrease in the GSIS and whether it is possible to counteract this desensitization by SVS. We also tested the impact of the incretin glucagon-like peptide-1 (GLP-1) on the GB-induced desensitization. After 24-hour preincubation with GB in combination with SVS or GLP-1, we measured the basal and glucose-stimulated insulin responses and the total islet insulin content. We also determined the fold change in gene expression of pancreatic and duodenal homeobox 1 and glucose transporter isoform 2. After 24-hour preincubation in 11.1 mmol/L glucose, GB (10(-11)-10(-3) mol/L) caused a dose-dependent decrease in GSIS (16.7 mmol/L glucose) (P < .001). GB (10(-7) mol/L) pretreatment elevated BIS, but neither SVS (10(-7) mol/L) nor GLP-1 (10(-7) mol/L) could reverse this. Interestingly, the GB-induced desensitization of GSIS was counteracted by both SVS (P < .05) and GLP-1 (P < .05). SVS reversed the decrease in insulin content caused by GB pretreatment (P < .05). GB pretreatment did not change gene expression of pancreatic and duodenal homeobox 1 nor glucose transporter isoform 2, whereas SVS significantly up-regulated the expression of both genes by more than 2-fold (P < .05). Our results showed that SVS in combination with GB did not reverse GB-induced increase in BIS, whereas both SVS and GLP-1 counteracted GB-induced desensitization of GSIS. SVS is able to counteract the desensitizing effects of GB and may be a

  12. Rap1 promotes multiple pancreatic islet cell functions and signals through mammalian target of rapamycin complex 1 to enhance proliferation.

    PubMed

    Kelly, Patrick; Bailey, Candice L; Fueger, Patrick T; Newgard, Christopher B; Casey, Patrick J; Kimple, Michelle E

    2010-05-21

    Recent studies have implicated Epac2, a guanine-nucleotide exchange factor for the Rap subfamily of monomeric G proteins, as an important regulator of insulin secretion from pancreatic beta-cells. Although the Epac proteins were originally identified as cAMP-responsive activators of Rap1 GTPases, the role of Rap1 in beta-cell biology has not yet been defined. In this study, we examined the direct effects of Rap1 signaling on beta-cell biology. Using the Ins-1 rat insulinoma line, we demonstrate that activated Rap1A, but not related monomeric G proteins, promotes ribosomal protein S6 phosphorylation. Using isolated rat islets, we show that this signaling event is rapamycin-sensitive, indicating that it is mediated by the mammalian target of rapamycin complex 1-p70 S6 kinase pathway, a known growth regulatory pathway. This newly defined beta-cell signaling pathway acts downstream of cAMP, in parallel with the stimulation of cAMP-dependent protein kinase, to drive ribosomal protein S6 phosphorylation. Activated Rap1A promotes glucose-stimulated insulin secretion, islet cell hypertrophy, and islet cell proliferation, the latter exclusively through mammalian target of rapamycin complex 1, suggesting that Rap1 is an important regulator of beta-cell function. This newly defined signaling pathway may yield unique targets for the treatment of beta-cell dysfunction in diabetes. PMID:20339002

  13. Pancreatic polypepetide inhibits pancreatic enzyme secretion via a cholinergic pathway

    SciTech Connect

    Jung, G.; Louie, D.S.; Owyang, C. )

    1987-11-01

    In rat pancreatic slices, rat pancreatic polypeptide (PP) or C-terminal hexapeptide of PP (PP-(31-36)) inhibited potassium-stimulated amylase release in a dose-dependent manner. The inhibition was unaffected by addition of hexamethonium but blocked by atropine. In contrast, PP-(31-36) did not have any effect on acetylcholine- or cholecystokinin octapeptide-stimulated amylase release. In addition, when pancreatic slices were incubated with ({sup 3}H)choline, PP-(31-36) inhibited the potassium-evoked release of synthesized ({sup 3}H)acetylcholine in a dose-dependent manner. The inhibitory action of PP was unaffected by adrenergic, dopaminergic, or opioid receptor antagonists. Thus PP inhibits pancreatic enzyme secretion via presynaptic modulation of acetylcholine release. This newly identified pathway provides a novel mechanism for hormonal inhibition of pancreatic enzyme secretion via modulation of the classic neurotransmitter function.

  14. Chronic Pancreatitis

    PubMed Central

    DiMagno, Matthew J.; DiMagno, Eugene P.

    2012-01-01

    Purpose of review We review important new clinical observations in chronic pancreatitis (CP) reported in 2011. Recent findings Smoking increases the risk of non-gallstone acute pancreatitis (AP) and the progression of AP to CP. Binge drinking during Oktoberfest did not associate with increased hospital admissions for AP. The unfolded protein response is an adaptive mechanism to maintain pancreatic health in response to noxious stimuli such as alcohol. Onset of diabetes mellitus in CP is likely due to progressive disease rather than individual variables. Insufficient pancreatic enzyme dosing is common for treatment of pancreatic steatorrhea; 90,000 USP U of lipase should be given with meals. Surgical drainage provides sustained, superior pain relief compared to endoscopic treatment in patients advanced CP with a dilated main duct +/− pancreatic stones. The central acting gabapentoid pregabalin affords a modest 12% pain reduction in patients with CP but ~30% of patients have significant side effects. Summary Patients with non-gallstone related AP or CP of any etiology should cease smoking. Results of this year’s investigations further elucidated the pancreatic pathobiology due to alcohol, onset of diabetes mellitus in CP, and the mechanisms and treatment of neuropathic pain in CP. PMID:22782018

  15. Uses of esophageal function testing: dysphagia.

    PubMed

    Yazaki, Etsuro; Woodland, Philip; Sifrim, Daniel

    2014-10-01

    Esophageal function testing should be used for differential diagnosis of dysphagia. Dysphagia can be the consequence of hypermotility or hypomotility of the muscles of the esophagus. Decreased esophageal or esophagogastric junction distensibility can provoke dysphagia. The most well established esophageal dysmotility is achalasia. Other motility disorders can also cause dysphagia. High-resolution manometry (HRM) is the gold standard investigation for esophageal motility disorders. Simultaneous measurement of HRM and intraluminal impedance can be useful to assess motility and bolus transit. Impedance planimetry measures distensibility of the esophageal body and gastroesophageal junction in patients with achalasia and eosinophilic esophagitis. PMID:25216909

  16. Pancreatic abnormalities and AIDS related sclerosing cholangitis.

    PubMed Central

    Teare, J P; Daly, C A; Rodgers, C; Padley, S P; Coker, R J; Main, J; Harris, J R; Scullion, D; Bray, G P; Summerfield, J A

    1997-01-01

    OBJECTIVES: Biliary tract abnormalities are well recognised in AIDS, most frequently related to opportunistic infection with Cryptosporidium, Microsporidium, and cytomegalovirus. We noted a high frequency of pancreatic abnormalities associated with biliary tract disease. To define these further we reviewed the clinical and radiological features in these patients. METHODS: Notes and radiographs were available from two centres for 83 HIV positive patients who had undergone endoscopic retrograde cholangiopancreatography for the investigation of cholestatic liver function tests or abdominal pain. RESULTS: 56 patients had AIDS related sclerosing cholangitis (ARSC); 86% of these patients had epigastric or right upper quadrant pain and 52% had hepatomegaly. Of the patients with ARSC, 10 had papillary stenosis alone, 11 had intra- and extrahepatic sclerosing cholangitis alone, and 35 had a combination of the two. Ampullary biopsies performed in 24 patients confirmed an opportunistic infection in 16. In 15 patients, intraluminal polyps were noted on the cholangiogram. Pancreatograms were available in 34 of the 45 patients with papillary stenosis, in which 29 (81%) had associated pancreatic duct dilatation, often with associated features of chronic pancreatitis. In the remaining 27 patients, final diagnoses included drug induced liver disease, acalculous cholecystitis, gall bladder empyema, chronic B virus hepatitis, and alcoholic liver disease. CONCLUSION: Pancreatic abnormalities are commonly seen with ARSC and may be responsible for some of the pain not relieved by biliary sphincterotomy. The most frequent radiographic biliary abnormality is papillary stenosis combined with ductal sclerosis. Images PMID:9389948

  17. Detection, Evaluation and Treatment of Diabetes Mellitus in Chronic Pancreatitis: Recommendations from PancreasFest 2012

    PubMed Central

    Rickels, Michael R.; Bellin, Melena; Toledo, Frederico G.S.; Robertson, R. Paul; Andersen, Dana K.; Chari, Suresh T.; Brand, Randall; Frulloni, Luca; Anderson, Michelle A.; Whitcomb, David C.

    2013-01-01

    Description Diabetes and glucose intolerance are common complications of chronic pancreatitis, yet clinical guidance on their detection, classification, and management is lacking. Methods A working group reviewed the medical problems, diagnostic methods, and treatment options for chronic pancreatitis-associated diabetes for a consensus meeting at PancreasFest 2012. Results Guidance Statement 1.1 Diabetes mellitus is common in chronic pancreatitis. While any patient with chronic pancreatitis should be monitored for development of diabetes, those with long-standing duration of disease, prior partial pancreatectomy, and early onset of calcific disease may be at higher risk. Those patients developing diabetes mellitus are likely to have co-existing pancreatic exocrine insufficiency. Guidance Statement 1.2 Diabetes occurring secondary to chronic pancreatitis should be recognized as pancreatogenic diabetes (type 3c diabetes). Guidance Statement 2.1 The initial evaluation should include fasting glucose and HbA1c. These tests should be repeated annually. Impairment in either fasting glucose or HbA1c requires further evaluation. Guidance Statement 2.2 Impairment in either fasting glucose or HbA1c should be further evaluated by a standard 75 gram oral glucose tolerance test. Guidance Statement 2.3 An absent pancreatic polypeptide response to mixed-nutrient ingestion is a specific indicator of type 3c diabetes. Guidance Statement 2.4 Assessment of pancreatic endocrine reserve, and importantly that of functional beta-cell mass, should be performed as part of the evaluation and follow-up for total pancreatectomy with islet autotransplantation (TPIAT). Guidance Statement 3 Patients with pancreatic diabetes shall be treated with specifically tailored medical nutrition and pharmacologic therapies. Conclusions Physicians should evaluate and treat glucose intolerance in patients with pancreatitis. PMID:23890130

  18. Collagen esterification enhances the function and survival of pancreatic β cells in 2D and 3D culture systems

    SciTech Connect

    Ko, Jae Hyung; Kim, Yang Hee; Jeong, Seong Hee; Lee, Song; Park, Si-Nae; Shim, In Kyong; Kim, Song Cheol

    2015-08-07

    Collagen, one of the most important components of the extracellular matrix (ECM), may play a role in the survival of pancreatic islet cells. In addition, chemical modifications that change the collagen charge profile to a net positive charge by esterification have been shown to increase the adhesion and proliferation of various cell types. The purpose of this study was to characterize and compare the effects of native collagen (NC) and esterified collagen (EC) on β cell function and survival. After isolation by the collagenase digestion technique, rat islets were cultured with NC and EC in 2 dimensional (2D) and 3 dimensional (3D) environments for a long-term duration in vitro. The cells were assessed for islet adhesion, morphology, viability, glucose-induced insulin secretion, and mRNA expression of glucose metabolism-related genes, and visualized by scanning electron microscopy (SEM). Islet cells attached tightly in the NC group, but islet cell viability was similar in both the NC and EC groups. Glucose-stimulated insulin secretion was higher in the EC group than in the NC group in both 2D and 3D culture. Furthermore, the mRNA expression levels of glucokinase in the EC group were higher than those in the NC group and were associated with glucose metabolism and insulin secretion. Finally, SEM observation confirmed that islets had more intact component cells on EC sponges than on NC sponges. These results indicate that modification of collagen may offer opportunities to improve function and viability of islet cells. - Highlights: • We changed the collagen charge profile to a net positive charge by esterification. • Islets cultured on esterified collagen improved survival in both 2D and 3D culture. • Islets cultured on esterified collagen enhanced glucose-stimulated insulin release. • High levels of glucokinase mRNA may be associated with increased insulin release.

  19. Functional Task Test: 2. Spaceflight-Induced Cardiovascular Change and Recovery During NASA's Functional Task Test

    NASA Technical Reports Server (NTRS)

    Phillips, Tiffany; Arzeno, Natalia M.; Stenger, Michael; Lee, Stuart M. C.; Bloomberg, Jacob J.; Platts, Steven H.

    2011-01-01

    The overall objective of the functional task test (FTT) is to correlate spaceflight-induced physiological adaptations with changes in performance of high priority exploration mission-critical tasks. This presentation will focus on the recovery from fall/stand test (RFST), which measures the cardiovascular response to the transition from the prone posture (simulated fall) to standing in normal gravity, as well as heart rate (HR) during 11 functional tasks. As such, this test describes some aspects of spaceflight-induced cardiovascular deconditioning and the course of recovery in Space Shuttle and International Space Station (ISS) astronauts. The sensorimotor and neuromuscular components of the FTT are described in two separate abstracts: Functional Task Test 1 and 3.

  20. Chronic pancreatitis

    MedlinePlus

    ... body Blockage of the tubes (ducts) that drain enzymes from the pancreas Cystic fibrosis High levels of a fat, called ... Limiting caffeine The health care provider may prescribe pancreatic enzymes. You must take these medicines with every meal. ...

  1. Acute pancreatitis

    MedlinePlus

    ... sure children receive vaccines to protect them against mumps and other childhood illnesses. Treat medical problems that ... Heart failure - overview Hemolytic-uremic syndrome Kawasaki disease Mumps Mycoplasma pneumonia Reye syndrome Patient Instructions Pancreatitis - discharge ...

  2. Pancreatic Diseases

    MedlinePlus

    ... and in front of your spine. It produces juices that help break down food and hormones that help control blood sugar levels. Problems with the pancreas can lead to many health problems. These include Pancreatitis, or inflammation of the ...

  3. Pancreatic Cancer

    MedlinePlus

    ... sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for ... therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells. NIH: National Cancer Institute

  4. Integrated Locomotor Function Tests for Countermeasure Evaluation

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Landsness, E. C.; Black, F. O.

    2005-01-01

    Following spaceflight crewmembers experience locomotor dysfunction due to inflight adaptive alterations in sensorimotor function. Countermeasures designed to mitigate these postflight gait alterations need to be assessed with a new generation of tests that evaluate the interaction of various sensorimotor sub-systems central to locomotor control. The goal of the present study was to develop new functional tests of locomotor control that could be used to test the efficacy of countermeasures. These tests were designed to simultaneously examine the function of multiple sensorimotor systems underlying the control of locomotion and be operationally relevant to the astronaut population. Traditionally, gaze stabilization has been studied almost exclusively in seated subjects performing target acquisition tasks requiring only the involvement of coordinated eye-head movements. However, activities like walking involve full-body movement and require coordination between lower limbs and the eye-head-trunk complex to achieve stabilized gaze during locomotion. Therefore the first goal of this study was to determine how the multiple, interdependent, full-body sensorimotor gaze stabilization subsystems are functionally coordinated during locomotion. In an earlier study we investigated how alteration in gaze tasking changes full-body locomotor control strategies. Subjects walked on a treadmill and either focused on a central point target or read numeral characters. We measured: temporal parameters of gait, full body sagittal plane segmental kinematics of the head, trunk, thigh, shank and foot, accelerations along the vertical axis at the head and the shank, and the vertical forces acting on the support surface. In comparison to the point target fixation condition, the results of the number reading task showed that compensatory head pitch movements increased, peak head acceleration was reduced and knee flexion at heel-strike was increased. In a more recent study we investigated the

  5. Autoimmune pancreatitis.

    PubMed

    Omiyale, Ayodeji Oluwarotimi

    2016-06-01

    Autoimmune pancreatitis (AIP) is a rare, distinct and increasingly recognized form of pancreatitis which has autoimmune features. The international consensus diagnostic criteria (ICDC) for AIP recently described two subtypes; type 1[lymphoplasmacytic sclerosing pancreatitis (LPSP)] and type 2 [idiopathic duct-centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesion (GEL)]. Type 1 is the more common form of the disease worldwide and current understanding suggests that it is a pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). In contrast, type 2 AIP is a pancreas-specific disease not associated with IgG4 and mostly without the overt extra-pancreatic organ involvement seen in type 1. The pathogenesis of AIP is not completely understood and its clinical presentation is non-specific. It shares overlapping features with more sinister pathologies such as cancer of the pancreas, which continues to pose a diagnostic challenge for clinicians. The diagnostic criteria requires a variable combination of histopathological, imaging and serological features in the presence of typical extrapancreatic lesions and a predictable response to steroids. PMID:27294040

  6. Autoimmune pancreatitis

    PubMed Central

    2016-01-01

    Autoimmune pancreatitis (AIP) is a rare, distinct and increasingly recognized form of pancreatitis which has autoimmune features. The international consensus diagnostic criteria (ICDC) for AIP recently described two subtypes; type 1[lymphoplasmacytic sclerosing pancreatitis (LPSP)] and type 2 [idiopathic duct-centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesion (GEL)]. Type 1 is the more common form of the disease worldwide and current understanding suggests that it is a pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). In contrast, type 2 AIP is a pancreas-specific disease not associated with IgG4 and mostly without the overt extra-pancreatic organ involvement seen in type 1. The pathogenesis of AIP is not completely understood and its clinical presentation is non-specific. It shares overlapping features with more sinister pathologies such as cancer of the pancreas, which continues to pose a diagnostic challenge for clinicians. The diagnostic criteria requires a variable combination of histopathological, imaging and serological features in the presence of typical extrapancreatic lesions and a predictable response to steroids. PMID:27294040

  7. Mass production of functional human pancreatic β-cells: why and how?

    PubMed

    Scharfmann, R; Didiesheim, M; Richards, P; Chandra, V; Oshima, M; Albagli, O

    2016-09-01

    Diabetes (either type 1 or type 2) is due to insufficient functional β-cell mass. Research has, therefore, aimed to discover new ways to maintain or increase either β-cell mass or function. For this purpose, rodents have mainly been used as model systems and a large number of discoveries have been made. Meanwhile, although we have learned that rodent models represent powerful systems to model β-cell development, function and destruction, we realize that there are limitations when attempting to transfer the data to what is occurring in humans. Indeed, while human β-cells share many similarities with rodent β-cells, they also differ on a number of important parameters. In this context, developing ways to study human β-cell development, function and death represents an important challenge. This review will describe recent data on the development and use of convenient sources of human β-cells that should be useful tools to discover new ways to modulate functional β-cell mass in humans. PMID:27615142

  8. Pancreatic Cancer Early Detection Program

    ClinicalTrials.gov

    2014-07-30

    Pancreatic Cancer; Pancreas Cancer; Pancreatic Adenocarcinoma; Familial Pancreatic Cancer; BRCA 1/2; HNPCC; Lynch Syndrome; Hereditary Pancreatitis; FAMMM; Familial Atypical Multiple Mole Melanoma; Peutz Jeghers Syndrome

  9. Groove Pancreatitis: A Rare form of Chronic Pancreatitis

    PubMed Central

    Jani, Bharivi; Rzouq, Fadi; Saligram, Shreyas; Nawabi, Atta; Nicola, Marian; Dennis, Katie; Ernst, Carly; Abbaszadeh, Ali; Bonino, John; Olyaee, Mojtaba

    2015-01-01

    Context: Groove pancreatitis is a rare form of chronic pancreatitis affecting the “groove” of the pancreas among the pancreatic head, duodenum, and common bile duct. The exact cause is unknown, although there are associations with long-term alcohol abuse, smoking, peptic ulcer disease, heterotopic pancreas, gastric resection, biliary disease, and anatomical or functional obstruction of the minor papilla. The diagnosis can be challenging. Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography are the preferred imaging modalities. The treatment of choice is conservative although surgical intervention can sometimes be required. Case Report: A 57-year-old male with a history of human immunodeficiency virus and hepatitis B presented with 4 days of epigastric pain. Abdominal exam revealed absent bowel sounds and epigastric tenderness. He had a creatinine of 1.72 mg/dL, potassium of 2.9 mmol/L, and a normal lipase level of 86 U/L. Liver enzymes and total bilirubin were normal. Computed tomography abdomen showed high-grade obstruction of the second portion of the duodenum without any obvious mass. An esophagogastroduodenoscopy showed a mass at the duodenal bulb causing luminal narrowing, with biopsies negative for malignancy. Magnetic resonance imaging revealed a mass in the region of the pancreatic head and descending duodenum. EUS revealed a 3 cm mass in the region of pancreatic head with irregular borders and no vascular invasion. Fine needle aspiration (FNA) was nondiagnostic. The patient then underwent a Whipple's procedure. Pathology of these specimens was negative for malignancy but was consistent with para-duodenal or groove pancreatitis. Conclusion: The low incidence of groove pancreatitis is partly due to lack of familiarity with the disease. Groove pancreatitis should be considered in the differential for patients presenting with pancreatic head lesions and no cholestatic jaundice, especially when a duodenal obstruction is present, and

  10. Antibody Response to Serpin B13 Induces Adaptive Changes in Mouse Pancreatic Islets and Slows Down the Decline in the Residual Beta Cell Function in Children with Recent Onset of Type 1 Diabetes Mellitus.

    PubMed

    Kryvalap, Yury; Lo, Chi-Wen; Manuylova, Ekaterina; Baldzizhar, Raman; Jospe, Nicholas; Czyzyk, Jan

    2016-01-01

    Type 1 diabetes mellitus (T1D) is characterized by a heightened antibody (Ab) response to pancreatic islet self-antigens, which is a biomarker of progressive islet pathology. We recently identified a novel antibody to clade B serpin that reduces islet-associated T cell accumulation and is linked to the delayed onset of T1D. As natural immunity to clade B arises early in life, we hypothesized that it may influence islet development during that time. To test this possibility healthy young Balb/c male mice were injected with serpin B13 mAb or IgG control and examined for the number and cellularity of pancreatic islets by immunofluorescence and FACS. Beta cell proliferation was assessed by measuring nucleotide analog 5-ethynyl-2'-deoxyuridine (5-EdU) incorporation into the DNA and islet Reg gene expression was measured by real time PCR. Human studies involved measuring anti-serpin B13 autoantibodies by Luminex. We found that injecting anti-serpin B13 monoclonal Ab enhanced beta cell proliferation and Reg gene expression, induced the generation of ∼80 pancreatic islets per animal, and ultimately led to increase in the beta cell mass. These findings are relevant to human T1D because our analysis of subjects just diagnosed with T1D revealed an association between baseline anti-serpin activity and slower residual beta cell function decline in the first year after the onset of diabetes. Our findings reveal a new role for the anti-serpin immunological response in promoting adaptive changes in the endocrine pancreas and suggests that enhancement of this response could potentially help impede the progression of T1D in humans. PMID:26578518

  11. Differentially expressed microRNA identification and target gene function analysis in starvation-induced autophagy of AR42J pancreatic acinar cells.

    PubMed

    Gao, Bo; Wang, Duanping; Sun, Wang; Meng, Xianzhi; Zhang, Weihui; Xue, Dongbo

    2016-07-01

    Acute pancreatitis (AP) is a common acute digestive tract disease, with increased morbidity and mortality, and an unclear pathogenesis. Trypsinogen activation in pancreatic acinar cells may be the primary mechanism underlying the development of AP. Previous studies reported that autophagy participates in the formation of acinar cell vacuoles in AP and in the process of trypsinogen activation as an important cause of AP. Furthermore, microRNAs (miRNAs) maintain the autophagy process by regulating the expression of autophagy‑associated genes. In the present study, an in vitro pancreatic acinar cell autophagy model was established using the AR42J starvation‑induced pancreatic acinar cell line. Twenty differentially expressed microRNAs were identified using miRNA microarray. Bioinformatics analysis was used to predict the target genes of miRNAs and analyze the functions of differentially expressed miRNAs. The results demonstrated that only the downregulated miRNA rno‑miR‑148b‑3p predicted 593 target genes with a statistical significance (P<0.05), from which 10 genes were autophagy‑associated. The results of gene ontology and pathway analyses demonstrated that the target genes of miRNAs were enriched in the Response to insulin stimulus, Regulation of cell death and the Insulin signaling pathways (P<0.05, FDR<0.05). In addition, protein‑protein interaction network analysis demonstrated a widespread interaction among the 593 target genes. The results of the present study may provide novel targets for research on the mechanisms of autophagy-promoted AP and AP treatment. PMID:27175615

  12. Beyond the brain: disrupted in schizophrenia 1 regulates pancreatic β-cell function via glycogen synthase kinase-3β.

    PubMed

    Jurczyk, Agata; Nowosielska, Anetta; Przewozniak, Natalia; Aryee, Ken-Edwin; DiIorio, Philip; Blodgett, David; Yang, Chaoxing; Campbell-Thompson, Martha; Atkinson, Mark; Shultz, Leonard; Rittenhouse, Ann; Harlan, David; Greiner, Dale; Bortell, Rita

    2016-02-01

    Individuals with schizophrenia and their first-degree relatives have higher rates of type 2 diabetes (T2D) than the general population (18-30 vs. 1.2-6.3%), independent of body mass index and antipsychotic medication, suggesting shared genetic components may contribute to both diseases. The cause of this association remains unknown. Mutations in disrupted in schizophrenia 1 (DISC1) increase the risk of developing psychiatric disorders [logarithm (base 10) of odds = 7.1]. Here, we identified DISC1 as a major player controlling pancreatic β-cell proliferation and insulin secretion via regulation of glycogen synthase kinase-3β (GSK3β). DISC1 expression was enriched in developing mouse and human pancreas and adult β- and ductal cells. Loss of DISC1 function, through siRNA-mediated depletion or expression of a dominant-negative truncation that models the chromosomal translocation of human DISC1 in schizophrenia, resulted in decreased β-cell proliferation (3 vs. 1%; P < 0.01), increased apoptosis (0.1 vs. 0.6%; P < 0.01), and glucose intolerance in transgenic mice. Insulin secretion was reduced (0.5 vs. 0.1 ng/ml; P < 0.05), and critical β-cell transcription factors Pdx1 and Nkx6.1 were significantly decreased. Impaired DISC1 allowed inappropriate activation of GSK3β in β cells, and antagonizing GSK3β (SB216763; IC50 = 34.3 nM) rescued the β-cell defects. These results uncover an unexpected role for DISC1 in normal β-cell physiology and suggest that DISC1 dysregulation contributes to T2D independently of its importance for cognition. PMID:26546129

  13. Functional role of an islet transcription factor, INSM1/IA-1, on pancreatic acinar cell trans-differentiation

    PubMed Central

    Zhang, Tao; Saunee, Nicolle A.; Breslin, Mary B.; Song, Kejing; Lan, Michael S.

    2011-01-01

    In this study, the functional role of INSM1 is examined with an AR42J acinar cell model for trans-differentiation into insulin-positive cells. Islet transcription factors (ITFs: INSM1, Pdx-1, and NeuroD1) are over-expressed in AR42J cells using adenoviral vectors. Addition of Ad-INSM1 alone or the combination of three ITFs to the AR42J cells triggers cellular trans-differentiation. Ectopic expression of INSM1 directly induces insulin, Pax6, and Nkx6.1 expression, whereas Pdx-1 and NeuroD1 were slightly suppressed by INSM1. Addition of Pdx-1 and NeuroD1 with INSM1 further enhances endocrine trans-differentiation by increasing both the numbers and intensity of the insulin positive cells with simultaneous activation of ITFs, Ngn3 and MafA. INSM1 expression alone partially inhibits dexamethasone-induced exocrine amylase expression. The combination of the three ITFs completely inhibits amylase expression and concomitantly induces greater acinar cell trans-differentiation into endocrine cells. Also, addition of the three ITFs promotes EGF and TGFβ receptors expression. Stimulation by the three ITFs along with the EGF/TGFβ growth factors strongly promotes insulin gene expression. The combination of the three ITFs and EGF/TGFβ growth factors with the primary cultured pancreatic acini also facilitates exocrine to endocrine cell differentiation. Taken together, both the AR42J cell line and the primary cultured mouse acinar cells support INSM1 induced acini trans-differentiation model. PMID:21830214

  14. Diabetogenic effect of cyclosporin A is mediated by interference with mitochondrial function of pancreatic B-cells.

    PubMed

    Düfer, M; Krippeit-Drews, P; Lembert, N; Idahl, L A; Drews, G

    2001-10-01

    Treatment of patients after organ transplantation with the immunosuppressive drug cyclosporin A (CsA) is often accompanied by impaired glucose tolerance, thus promoting the development of diabetes mellitus. In the present article we show that 2 to 5 microM CsA diminishes glucose-induced insulin secretion of isolated mouse pancreatic islets in vitro by inhibiting glucose-stimulated oscillations of the cytoplasmic free-Ca(2+) concentration [Ca(2+)](c). This effect is not due to an inhibition of calcineurin, which mediates the immunosuppressive effect of CsA, because other calcineurin inhibitors, deltamethrin and tacrolimus, did not affect the oscillations in [Ca(2+)](c) of the B-cells. The CsA-induced decrease in [Ca(2+)](c) to basal values was not caused by a direct inhibition of L-type Ca(2+) channels. CsA is known to be a potent inhibitor of the mitochondrial permeability transition pore (PTP), which we recently suggested to be involved in the regulation of oscillations. Consequently, CsA also inhibited the oscillations of the cell membrane potential, and it is shown that these effects could not be ascribed to cellular ATP depletion. However, the mitochondrial membrane potential Delta Psi was affected by CsA by inhibiting the oscillations in Delta Psi. Interestingly, the observed reduction in [Ca(2+)](c) could be counteracted by the K(+)(ATP) channel blocker tolbutamide, indicating that the stimulus-secretion coupling was interrupted before the closure of K(+)(ATP) channels. It is concluded that CsA alters B-cell function by inhibiting the mitochondrial PTP. This terminates the oscillatory activity that is indispensable for adequate insulin secretion. Thus, CsA acts on different targets to induce the immunosuppressive and the diabetogenic effect. PMID:11562451

  15. Half-antibody functionalized lipid-polymer hybrid nanoparticles for targeted drug delivery to carcinoembryonic antigen presenting pancreatic cancer cells.

    PubMed

    Hu, Che-Ming Jack; Kaushal, Sharmeela; Tran Cao, Hop S; Aryal, Santosh; Sartor, Marta; Esener, Sadik; Bouvet, Michael; Zhang, Liangfang

    2010-06-01

    Current chemotherapy regimens against pancreatic cancer are met with little success as poor tumor vascularization significantly limits the delivery of oncological drugs. High-dose targeted drug delivery, through which a drug delivery vehicle releases a large payload upon tumor localization, is thus a promising alternative strategy against this lethal disease. Herein, we synthesize anti-carcinoembryonic antigen (CEA) half-antibody conjugated lipid-polymer hybrid nanoparticles and characterize their ligand conjugation yields, physicochemical properties, and targeting ability against pancreatic cancer cells. Under the same drug loading, the half-antibody targeted nanoparticles show enhanced cancer killing effect compared to the corresponding nontargeted nanoparticles. PMID:20394436

  16. Glucagon release from rat pancreatic islets. A combined morphological and functional approach.

    PubMed Central

    Carpentier, J L; Malaisse-Lagae, F; Müller, W A

    1977-01-01

    The release of glucagon induced in isolated rat islets by arginine or by calcium deprivation has been subjected to combined functional and morphological quantifications. Arginine-stimulated glucagon release was associated with a significant increase of morphological events linked to exocytosis. By contrast, the paradoxical events linked to exocytosis. By contrast, the paradoxical release of glucagon provoked by calcium deprivation, although accompanied by a significant loss of granule stores, was not associated with an increase of morphologically detectable exocytosis. Images PMID:409734

  17. Nkx6.1 is essential for maintaining the functional state of pancreatic beta cells.

    PubMed

    Taylor, Brandon L; Liu, Fen-Fen; Sander, Maike

    2013-09-26

    Recently, loss of beta-cell-specific traits has been proposed as an early cause of beta cell failure in diabetes. However, the molecular mechanisms that underlie the loss of beta cell features remain unclear. Here, we identify an Nkx6.1-controlled gene regulatory network as essential for maintaining the functional and molecular traits of mature beta cells. Conditional Nkx6.1 inactivation in adult mice caused rapid-onset diabetes and hypoinsulinemia. Genome-wide analysis of Nkx6.1-regulated genes and functional assays further revealed a critical role for Nkx6.1 in the control of insulin biosynthesis, insulin secretion, and beta cell proliferation. Over time, Nkx6.1-deficient beta cells acquired molecular characteristics of delta cells, revealing a molecular link between impaired beta cell functional properties and loss of cell identity. Given that Nkx6.1 levels are reduced in human type 2 diabetic beta cells, our study lends support to the concept that loss of beta cell features could contribute to the pathogenesis of diabetes. PMID:24035389

  18. Functional studies of rat, porcine, and human pancreatic islets cultured in ten commercially available media.

    PubMed

    Holmes, M A; Clayton, H A; Chadwick, D R; Bell, P R; London, N J; James, R F

    1995-10-27

    There have been no extensive studies investigating the effect of tissue culture media on the in vitro functional characteristics of rat, porcine and human Islets of Langerhans. We therefore aimed to compare ten commercially available tissue culture media on the basis of their ability to maintain islet viability. Following isolation, islets were cultured free-floating in the ten media (RPMI 1640-11mM glucose (control), RPMI 1640-2.2mM glucose, Dulbecco's MEM, TCM 199, CMRL 1066, Iscove's MEM, Waymouth's MEM, Serum-Free medium, Ex-cell 300, Ham's F-12) and viability was assessed after 24 hr, 3 days, and 7 days on the basis of macroscopic appearance, cell membrane integrity, and insulin secretion in response to glucose stimulation both by dynamic incubation and by perifusion. Each islet species demonstrated physiological insulin release characteristics in all media--however, it was possible to distinguish between the media by comparing the stimulation indices calculated from the insulin release studies. Significantly higher stimulation indices were produced in Iscove's MEM for rat islets, in Ham's F-12 for porcine islets and in CMRL 1066 for human islets. Over the entire culture period a significant deterioration in function was observed in all species cultured in the control media, although this was reversed when islets were cultured in the optimal media. Furthermore, in the case of porcine and human islets a significant improvement in function over the seven-day period was noted in the optimal media. In conclusion, of the commercially available media, the optimal tissue culture medium for rat islets is Iscove's MEM, for porcine islets is Ham's F-12, and for human islets is CMRL 1066. PMID:7482747

  19. New insight into the mechanisms underlying the function of the incretin hormone glucagon-like peptide-1 in pancreatic β-cells

    PubMed Central

    Xiong, Xiaoquan; Shao, Weijuan; Jin, Tianru

    2012-01-01

    During the past two decades, the exploration of function of two incretin hormones, namely glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP), has led to the development of two categories of novel therapeutic agents for diabetes and its complications, known as GLP-1 receptor (GLP-1R) agonists and DPP-IV inhibitors. Mechanisms underlying the function of GLP-1, however, still need to be further explored. GLP-1 not only functions as an incretin hormone in stimulating insulin secretion in response to nutritional, hormonal and neuronal stimulations, but also acts as an “insulin-like” factor in β-cell and extra-pancreatic organs. In addition to these insulinotropic and insulinomimetic effects, GLP-1 was shown to exert its protective effect in β-cell by repressing the expression of TxNIP, a mediator of glucolipotoxicity. A number of recent studies have shown that the Wnt signaling pathway effector, the bipartite transcription factor β-catenin/TCF, controls not only the production of GLP-1, but also the function of GLP-1. Furthermore, previously assumed “degradation” products of GLP-1(7–36)amide, including GLP-1(9–36)amide and GLP-1(28–36)amide, have been shown to exert beneficial effect in pancreas and extra-pancreatic tissues or cell lineages. Here we summarized our current knowledge on the metabolic, proliferative and protective effects of GLP-1(7–36)amide and its cleavage fragments, mainly focusing on pancreatic β-cells and the involvement of the Wnt signaling pathway effector β-catenin. PMID:23314611

  20. New insights into the role of connexins in pancreatic islet function and diabetes

    PubMed Central

    Farnsworth, Nikki L.; Benninger, Richard K.P.

    2014-01-01

    Multi-cellular systems require complex signaling mechanisms for proper tissue function, to mediate signaling between cells in close proximity and at distances. This holds true for the islets of Langerhans, which are multicellular micro-organs located in the pancreas responsible for glycemic control, through secretion of insulin and other hormones. Coupling of electrical and metabolic signaling between islet β-cells is required for proper insulin secretion and effective glycemic control. β-cell specific coupling is established through gap junctions composed of connexin36, which results in coordinated insulin release across the islet. Islet connexins have been implicated in both Type-1 and Type-2 diabetes; however a clear link remains to be determined. The goal of this review is to discuss recent discoveries regarding the role of connexins in regulating insulin secretion, the regulation of connexins within the islet, and recent studies which support a role for connexins in diabetes. Further studies which investigate the regulation of connexins in the islet and their role in diabetes may lead to novel diabetes therapies which regulate islet function and β-cell survival through modulation of gap junction coupling. PMID:24583073

  1. Chronic pancreatitis: A diagnostic dilemma

    PubMed Central

    Duggan, Sinead N; Ní Chonchubhair, Hazel M; Lawal, Oladapo; O’Connor, Donal B; Conlon, Kevin C

    2016-01-01

    Typical clinical symptoms of chronic pancreatitis are vague and non-specific and therefore diagnostic tests are required, none of which provide absolute diagnostic certainly, especially in the early stages of disease. Recently-published guidelines bring much needed structure to the diagnostic work-up of patients with suspected chronic pancreatitis. In addition, novel diagnostic modalities bring promise for the future. The assessment and diagnosis of pancreatic exocrine insufficiency remains challenging and this review contests the accepted perspective that steatorrhea only occurs with > 90% destruction of the gland. PMID:26900292

  2. Liraglutide-induced acute pancreatitis.

    PubMed

    Jeyaraj, Santhosh; Shetty, Ananth Samith; Kumar, Champat Raj Roopesh; Nanditha, Arun; Krishnamoorthy, Satheesh; Raghavan, Arun; Raghavan, K; Ramachandran, Ambady

    2014-01-01

    An obese lady of 51 year with Type 2 Diabetes Mellitus for 13 years was prescribed Liraglutide, a glucagon like peptide (GLP-1) analogue (Victoza) for glycaemic control and reduction of weight. She was on gliclazide and Insulin prior to initiation of Liraglutide. Eight weeks after initiation of GLP -1 analogue, she developed severe abdominal pain, nausea and vomiting. She was admitted to a private hospital and evaluated. Biochemical tests and CT scan revealed presence of pancreatitis and she was treated for acute pancreatitis. Liraglutide was withdrawn and symptoms subsided. Subsequent follow-up showed that pancreatic enzyme levels were normal. PMID:25327099

  3. Hanford tanks initiative test facility functions and requirements

    SciTech Connect

    Krieg, S.A., Fluor Daniel Hanford

    1997-03-01

    This document presents the functions and requirements for a test facility for testing single-shell tank waste retrieval equipment and systems for the Hanford Tanks Initiative (HTI) project. This effort includes review of previous test facility functions and requirements and conducting a workshop to develop specific functions and requirements for HTI testing needs. Functions and requirements for testing future retrieval systems that follow HTI are also identified.

  4. Rfx6 maintains the functional identity of adult pancreatic β cells.

    PubMed

    Piccand, Julie; Strasser, Perrine; Hodson, David J; Meunier, Aline; Ye, Tao; Keime, Céline; Birling, Marie-Christine; Rutter, Guy A; Gradwohl, Gérard

    2014-12-24

    Increasing evidence suggests that loss of β cell characteristics may cause insulin secretory deficiency in diabetes, but the underlying mechanisms remain unclear. Here, we show that Rfx6, whose mutation leads to neonatal diabetes in humans, is essential to maintain key features of functionally mature β cells in mice. Rfx6 loss in adult β cells leads to glucose intolerance, impaired β cell glucose sensing, and defective insulin secretion. This is associated with reduced expression of core components of the insulin secretion pathway, including glucokinase, the Abcc8/SUR1 subunit of KATP channels and voltage-gated Ca(2+) channels, which are direct targets of Rfx6. Moreover, Rfx6 contributes to the silencing of the vast majority of "disallowed" genes, a group usually specifically repressed in adult β cells, and thus to the maintenance of β cell maturity. These findings raise the possibility that changes in Rfx6 expression or activity may contribute to β cell failure in humans. PMID:25497096

  5. Formal functional test designs with a test representation language

    NASA Technical Reports Server (NTRS)

    Hops, J. M.

    1993-01-01

    The application of the category-partition method to the test design phase of hardware, software, or system test development is discussed. The method provides a formal framework for reducing the total number of possible test cases to a minimum logical subset for effective testing. An automatic tool and a formal language were developed to implement the method and produce the specification of test cases.

  6. Rfx6 Maintains the Functional Identity of Adult Pancreatic β Cells

    PubMed Central

    Piccand, Julie; Strasser, Perrine; Hodson, David J.; Meunier, Aline; Ye, Tao; Keime, Céline; Birling, Marie-Christine; Rutter, Guy A.; Gradwohl, Gérard

    2014-01-01

    Summary Increasing evidence suggests that loss of β cell characteristics may cause insulin secretory deficiency in diabetes, but the underlying mechanisms remain unclear. Here, we show that Rfx6, whose mutation leads to neonatal diabetes in humans, is essential to maintain key features of functionally mature β cells in mice. Rfx6 loss in adult β cells leads to glucose intolerance, impaired β cell glucose sensing, and defective insulin secretion. This is associated with reduced expression of core components of the insulin secretion pathway, including glucokinase, the Abcc8/SUR1 subunit of KATP channels and voltage-gated Ca2+ channels, which are direct targets of Rfx6. Moreover, Rfx6 contributes to the silencing of the vast majority of “disallowed” genes, a group usually specifically repressed in adult β cells, and thus to the maintenance of β cell maturity. These findings raise the possibility that changes in Rfx6 expression or activity may contribute to β cell failure in humans. PMID:25497096

  7. Pancreatic β cells require NeuroD to achieve and maintain functional maturity

    PubMed Central

    Gu, Chunyan; Stein, Gretchen H.; Pan, Ning; Goebbels, Sandra; Hörnberg, Hanna; Nave, Klaus-Armin; Herrera, Pedro; White, Peter; Kaestner, Klaus H.; Sussel, Lori; Lee, Jacqueline E.

    2010-01-01

    Summary NeuroD, an insulin transactivator, is critical for development of the endocrine pancreas, and NeuroD mutations cause MODY6 in humans. To investigate the role of NeuroD in differentiated β cells, we generated mice in which neuroD is deleted in insulin-expressing cells. These mice exhibit severe glucose intolerance. Islets lacking NeuroD respond poorly to glucose and display a glucose metabolic profile similar to immature β cells, featuring increased expression of glycolytic genes and LDH-A, elevated basal insulin secretion and O2 consumption, and overexpression of NPY. Moreover, the mutant islets appear to have defective KATP channel-mediated insulin secretion. Unexpectedly, virtually all insulin in the mutant mice is derived from ins2, whereas ins1 expression is almost extinguished. Overall, these results indicate that NeuroD is required for β cell maturation and demonstrate the importance of NeuroD in the acquisition and maintenance of fully functional glucose responsive β cells. PMID:20374962

  8. Somatostatin, somatostatin receptors, and pancreatic cancer.

    PubMed

    Li, Min; Fisher, William E; Kim, Hee Joon; Wang, Xiaoping; Brunicardi, Charles F; Chen, Changyi; Yao, Qizhi

    2005-03-01

    Somatostatin may play an important role in the regulation of cancer growth including pancreatic cancer by interaction with somatostatin receptors (SSTRs) on the cell surface. Five SSTRs were cloned, and the function of these SSTRs is addressed in this review. SSTR-2, SSTR-5, and SSTR-1 are thought to play major roles in inhibiting pancreatic cancer growth both in vitro and in vivo. SSTR-3 may be involved in mediating apoptosis, but the role of SSTR-4 is not clear. In most pancreatic cancers, functional SSTRs are absent. Reintroduction of SSTR genes has been shown to inhibit pancreatic cancer growth in cell cultures and animal models. PMID:15706439

  9. Difference gel electrophoresis identifies differentially expressed proteins in endoscopically collected pancreatic fluid.

    PubMed

    Paulo, Joao A; Lee, Linda S; Banks, Peter A; Steen, Hanno; Conwell, Darwin L

    2011-08-01

    Alterations in the pancreatic fluid proteome of individuals with chronic pancreatitis (CP) may offer insights into the development and progression of the disease. The endoscopic pancreatic function test (ePFT) can safely collect large volumes of pancreatic fluid that are potentially amenable to proteomic analyses using difference gel electrophoresis (DIGE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pancreatic fluid was collected endoscopically using the ePFT method following secretin stimulation from three individuals with severe CP and three chronic abdominal pain (CAP) controls. The fluid was processed to minimize protein degradation and the protein profiles of each cohort, as determined by DIGE and LC-MS/MS, were compared. This DIGE-LC-MS/MS analysis reveals proteins that are differentially expressed in CP compared with CAP controls. Proteins with higher abundance in pancreatic fluid from CP individuals include: actin, desmoplankin, α-1-antitrypsin, SNC73, and serotransferrin. Those of relatively lower abundance include carboxypeptidase B, lipase, α-1-antichymotrypsin, α-2-macroglobulin, actin-related protein (Arp2/3) subunit 4, glyceraldehyde-3-phosphate dehydrogenase, and protein disulfide isomerase. Endoscopic collection (ePFT) in tandem with DIGE-LC-MS/MS is a suitable approach for pancreatic fluid proteome analysis; however, further optimization of our protocol, as outlined herein, may improve proteome coverage in future analyses. PMID:21792986

  10. The Spatiotemporal Pattern of Glis3 Expression Indicates a Regulatory Function in Bipotent and Endocrine Progenitors during Early Pancreatic Development and in Beta, PP and Ductal Cells

    PubMed Central

    Kang, Hong Soon; Takeda, Yukimasa; Jeon, Kilsoo

    2016-01-01

    The transcription factor Glis-similar 3 (Glis3) has been implicated in the development of neonatal, type 1 and type 2 diabetes. In this study, we examined the spatiotemporal expression of Glis3 protein during embryonic and neonatal pancreas development as well as its function in PP cells. To obtain greater insights into the functions of Glis3 in pancreas development, we examined the spatiotemporal expression of Glis3 protein in a knockin mouse strain expressing a Glis3-EGFP fusion protein. Immunohistochemistry showed that Glis3-EGFP was not detectable during early pancreatic development (E11.5 and E12.5) and at E13.5 and 15.5 was not expressed in Ptf1a+ cells in the tip domains indicating that Glis3 is not expressed in multipotent pancreatic progenitors. Glis3 was first detectable at E13.5 in the nucleus of bipotent progenitors in the trunk domains, where it co-localized with Sox9, Hnf6, and Pdx1. It remained expressed in preductal and Ngn3+ endocrine progenitors and at later stages becomes restricted to the nucleus of pancreatic beta and PP cells as well as ductal cells. Glis3-deficiency greatly reduced, whereas exogenous Glis3, induced Ppy expression, as reported for insulin. Collectively, our study demonstrates that Glis3 protein exhibits a temporal and cell type-specific pattern of expression during embryonic and neonatal pancreas development that is consistent with a regulatory role for Glis3 in promoting endocrine progenitor generation, regulating insulin and Ppy expression in beta and PP cells, respectively, and duct morphogenesis. PMID:27270601

  11. The Spatiotemporal Pattern of Glis3 Expression Indicates a Regulatory Function in Bipotent and Endocrine Progenitors during Early Pancreatic Development and in Beta, PP and Ductal Cells.

    PubMed

    Kang, Hong Soon; Takeda, Yukimasa; Jeon, Kilsoo; Jetten, Anton M

    2016-01-01

    The transcription factor Glis-similar 3 (Glis3) has been implicated in the development of neonatal, type 1 and type 2 diabetes. In this study, we examined the spatiotemporal expression of Glis3 protein during embryonic and neonatal pancreas development as well as its function in PP cells. To obtain greater insights into the functions of Glis3 in pancreas development, we examined the spatiotemporal expression of Glis3 protein in a knockin mouse strain expressing a Glis3-EGFP fusion protein. Immunohistochemistry showed that Glis3-EGFP was not detectable during early pancreatic development (E11.5 and E12.5) and at E13.5 and 15.5 was not expressed in Ptf1a+ cells in the tip domains indicating that Glis3 is not expressed in multipotent pancreatic progenitors. Glis3 was first detectable at E13.5 in the nucleus of bipotent progenitors in the trunk domains, where it co-localized with Sox9, Hnf6, and Pdx1. It remained expressed in preductal and Ngn3+ endocrine progenitors and at later stages becomes restricted to the nucleus of pancreatic beta and PP cells as well as ductal cells. Glis3-deficiency greatly reduced, whereas exogenous Glis3, induced Ppy expression, as reported for insulin. Collectively, our study demonstrates that Glis3 protein exhibits a temporal and cell type-specific pattern of expression during embryonic and neonatal pancreas development that is consistent with a regulatory role for Glis3 in promoting endocrine progenitor generation, regulating insulin and Ppy expression in beta and PP cells, respectively, and duct morphogenesis. PMID:27270601

  12. [Liver, bile ducts and pancreatic diseases].

    PubMed

    Kanno, T

    1995-06-01

    A fundamental guideline for the use of test results concerning liver, bile duct and pancreatic diseases was proposed in 1991 from the Japan Society of Clinical Pathology (JSCP). This guideline was principally based on the document of 1988 from the Committee on liver function tests of the Japanese Society of Gastroenterology (JSG). The document from the JSG was revised in May, 1994. Also a guideline for selection of markers of hepatitis virus in hepatic disorders, was proposed in January, 1994 from the same Committee of JSG. Here, we reevaluated and discussed the JSCP guideline as taking into consideration the two 1994 JSG documents. PMID:7602802

  13. Differential effects of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide and metformin on pancreatic β-cell and insulin sensitivity during a standardized test meal in patients with type 2 diabetes.

    PubMed

    Mari, A; Del Prato, S; Ludvik, B; Milicevic, Z; de la Peña, A; Shurzinske, L; Karanikas, C A; Pechtner, V

    2016-08-01

    This substudy of the AWARD-3 trial evaluated the effects of the once-weekly glucagon-like peptide-1 receptor agonist, dulaglutide, versus metformin on glucose control, pancreatic function and insulin sensitivity, after standardized test meals in patients with type 2 diabetes. Meals were administered at baseline, 26 and 52 weeks to patients randomized to monotherapy with dulaglutide 1.5 mg/week (n = 133), dulaglutide 0.75 mg/week (n = 136), or metformin ≥1500 mg/day (n = 140). Fasting and postprandial serum glucose, insulin, C-peptide and glucagon levels were measured up to 3 h post-meal. β-cell function and insulin sensitivity were assessed using empirical variables and mathematical modelling. At 26 weeks, similar decreases in area under the curve for glucose [AUCglucose (0-3 h)] were observed among all groups. β-cell function [AUCinsulin /AUCglucose (0-3 h)] increased with dulaglutide and was unchanged with metformin (p ≤ 0.005, both doses). Dulaglutide improved insulin secretion rate at 9 mmol/l glucose (p ≤ 0.04, both doses) and β-cell glucose sensitivity (p = 0.004, dulaglutide 1.5 mg). Insulin sensitivity increased more with metformin versus dulaglutide. In conclusion, dulaglutide improves postprandial glycaemic control after a standardized test meal by enhancing β-cell function, while metformin exerts a greater effect on insulin sensitivity. PMID:27059816

  14. Pancreatic cancer.

    PubMed

    Kleeff, Jorg; Korc, Murray; Apte, Minoti; La Vecchia, Carlo; Johnson, Colin D; Biankin, Andrew V; Neale, Rachel E; Tempero, Margaret; Tuveson, David A; Hruban, Ralph H; Neoptolemos, John P

    2016-01-01

    Pancreatic cancer is a major cause of cancer-associated mortality, with a dismal overall prognosis that has remained virtually unchanged for many decades. Currently, prevention or early diagnosis at a curable stage is exceedingly difficult; patients rarely exhibit symptoms and tumours do not display sensitive and specific markers to aid detection. Pancreatic cancers also have few prevalent genetic mutations; the most commonly mutated genes are KRAS, CDKN2A (encoding p16), TP53 and SMAD4 - none of which are currently druggable. Indeed, therapeutic options are limited and progress in drug development is impeded because most pancreatic cancers are complex at the genomic, epigenetic and metabolic levels, with multiple activated pathways and crosstalk evident. Furthermore, the multilayered interplay between neoplastic and stromal cells in the tumour microenvironment challenges medical treatment. Fewer than 20% of patients have surgically resectable disease; however, neoadjuvant therapies might shift tumours towards resectability. Although newer drug combinations and multimodal regimens in this setting, as well as the adjuvant setting, appreciably extend survival, ∼80% of patients will relapse after surgery and ultimately die of their disease. Thus, consideration of quality of life and overall survival is important. In this Primer, we summarize the current understanding of the salient pathophysiological, molecular, translational and clinical aspects of this disease. In addition, we present an outline of potential future directions for pancreatic cancer research and patient management. PMID:27158978

  15. The alteration of profile analysis to accommodate testing functions

    NASA Technical Reports Server (NTRS)

    Myers, R. H.

    1979-01-01

    The development of a methodology was studied for testing differences among several pilot functions, where the data points represent averages at various frequencies. Topics discussed include: basic assumptions, hypothesis, profile analysis, alteration of profile analysis to accommodate testing functions, test and procedures, and power of tests.

  16. Overview of Exocrine Pancreatic Pathobiology

    PubMed Central

    Pandiri, Arun R

    2014-01-01

    Exocrine pancreas is a source of several enzymes that are essential for the digestive process. The exocrine pancreatic secretion is tightly regulated by the neuroendocrine system. The endocrine pancreas is tightly integrated anatomically and physiologically with the exocrine pancreas and modulates its function. Compound-induced pancreatitis is not a common event in toxicology or drug development but it becomes a significant liability when encountered. Understanding the species-specific differences in physiology is essential to understand the underlying pathobiology of pancreatic disease in animal models and its relevance to human disease. This review will mainly focus on understanding the morphology and physiology of the pancreas, unique islet-exocrine interactions, and pancreatitis. PMID:24190915

  17. Vaccine therapy for pancreatic cancer

    PubMed Central

    Salman, Bulent; Zhou, Donger; Jaffee, Elizabeth M; Edil, Barish H; Zheng, Lei

    2013-01-01

    Pancreatic cancer is a lethal disease and currently available therapies have significant limitations. Pancreatic cancer is thus an ideal setting for the development of novel treatment modalities such as immunotherapy. However, relevant obstacles must be overcome for immunotherapeutic regimens against pancreatic cancer to be successful. Vaccine therapy relies on the administration of biological preparations that include an antigen that (at least ideally) is specifically expressed by malignant cells, boosting the natural ability of the immune system to react against neoplastic cells. There are a number of ways to deliver anticancer vaccines. Potent vaccines stimulate antigen presentation by dendritic cells, hence driving the expansion of antigen-specific effector and memory T cells. Unlike vaccines given as a prophylaxis against infectious diseases, anticancer vaccines require the concurrent administration of agents that interfere with the natural predisposition of tumors to drive immunosuppression. The safety and efficacy of vaccines against pancreatic cancer are nowadays being tested in early phase clinical trials. PMID:24498551

  18. Chronic pancreatitis and cystic fibrosis

    PubMed Central

    Witt, H

    2003-01-01

    Recent discoveries of trypsinogen and trypsin inhibitor mutations in patients with chronic pancreatitis (CP) support the hypothesis that an inappropriate activation of pancreatic zymogens to active enzymes within the pancreatic parenchyma starts the inflammatory process. Current data suggest that CP may be inherited dominant, recessive, or complex as a result of mutations in the above mentioned or yet unidentified genes. Evaluation of patients with CP should include genetic testing. Cystic fibrosis (CF) is an autosomal recessive inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene and is characterised by pancreatic insufficiency and chronic bronchopulmonary infection. The progression and severity of pulmonary disease differs considerably between people with identical CFTR mutations and does not seem to correlate with the type or class of the CFTR mutation. The identification of further disease modifying genetic factors will increase the pathophysiological understanding and may help to identify new therapeutic targets. PMID:12651880

  19. Pancreatic Cancer Stage 3

    MedlinePlus

    ... historical Searches are case-insensitive Pancreatic Cancer Stage 3 Add to My Pictures View /Download : Small: 720x576 ... Large: 3000x2400 View Download Title: Pancreatic Cancer Stage 3 Description: Stage III pancreatic cancer; drawing shows cancer ...

  20. [Laboratory and instrumental diagnostics of pancreatic diseases].

    PubMed

    2011-01-01

    The review focuses on the potential of modern laboratory and instrumental diagnostics ofpancreatic diseases including various forms of chronic pancreatitis, pancreatic cancer, cysts and pseudocysts, calcificators and concrements, abscesses, neuroendocrine tumours, etc. Diagnostic criteria for exocrine pancreatic disorders, such as hyper- and hyposecretory (hyper- and hypoenzymatic) forms of chronic pancreatitis are described along with direct and indirect, invasive and non-invasive, probe-based and probe-free methods for their study. Special attention is given to instrumental visualization of structural and morphological changes in the pancreas under different pathological conditions. The description of methods for the study of pancreatic endocrine functions and diagnostics of pancreatic diseases is preceded by a brief anatomo-physiologic essay. PMID:22420188

  1. Functional Regulation of Sugar Assimilation by N-Glycan-specific Interaction of Pancreatic α-Amylase with Glycoproteins of Duodenal Brush Border Membrane*

    PubMed Central

    Asanuma-Date, Kimie; Hirano, Yuki; Le, Na; Sano, Kotone; Kawasaki, Nana; Hashii, Noritaka; Hiruta, Yoko; Nakayama, Ken-ichi; Umemura, Mariko; Ishikawa, Kazuhiko; Sakagami, Hiromi; Ogawa, Haruko

    2012-01-01

    Porcine pancreatic α-amylase (PPA) binds to N-linked glycans of glycoproteins (Matsushita, H., Takenaka, M., and Ogawa, H. (2002) J. Biol Chem., 277, 4680–4686). Immunostaining revealed that PPA is located at the brush-border membrane (BBM) of enterocytes in the duodenum and that the binding is inhibited by mannan but not galactan, indicating that PPA binds carbohydrate-specifically to BBM. The ligands for PPA in BBM were identified as glycoprotein N-glycans that are significantly involved in the assimilation of glucose, including sucrase-isomaltase (SI) and Na+/Glc cotransporter 1 (SGLT1). Binding of SI and SGLT1 in BBM to PPA was dose-dependent and inhibited by mannan. Using BBM vesicles, we found functional changes in PPA and its ligands in BBM due to the N-glycan-specific interaction. The starch-degrading activity of PPA and maltose-degrading activity of SI were enhanced to 240 and 175%, respectively, while Glc uptake by SGLT1 was markedly inhibited by PPA at high but physiologically possible concentrations, and the binding was attenuated by the addition of mannose-specific lectins, especially from Galanthus nivalis. Additionally, recombinant human pancreatic α-amylases expressed in yeast and purified by single-step affinity chromatography exhibited the same carbohydrate binding specificity as PPA in binding assays with sugar-biotinyl polymer probes. The results indicate that mammalian pancreatic α-amylases share a common carbohydrate binding activity and specifically bind to the intestinal BBM. Interaction with N-glycans in the BBM activated PPA and SI to produce much Glc on the one hand and to inhibit Glc absorption by enterocytes via SGLT1 in order to prevent a rapid increase in blood sugar on the other. PMID:22584580

  2. OAIS Functional Model Conformance Test: A Proposed Measurement

    ERIC Educational Resources Information Center

    Laughton, Paul

    2012-01-01

    Purpose: The purpose of this paper is to develop a test for data centres, repositories and archives to determine OAIS functional model conformance. The test developed was carried out among the World Data Centre (WDC) member data centres. The method used to develop the OAIS functional model conformance test is discussed, along with the test…

  3. Functional Literacy in Schoolchildren. Definition and Criteria of Test Selection.

    ERIC Educational Resources Information Center

    Bessemer, David W.; Spencer, Mary L.

    As part of the development of a functional literacy test for fourth through eigth grade children in Title I compensatory education programs, this report defines functional literacy for children and enumerates criteria for evaluating existing tests. Criteria for selection of a test include: (1) content, empirical, and construct validity; (2)…

  4. 20 CFR 718.103 - Pulmonary function tests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (MVV) is reported, the results of such test shall be obtained independently rather than calculated from the results of the FEV1. (b) All pulmonary function test results submitted in connection with a claim... within 10% of each other shall be sufficient. Pulmonary function test results developed in...

  5. Mimics of pancreatic ductal adenocarcinoma

    PubMed Central

    Kaza, Ravi K.; Azar, Shadi F.; Ruma, Julie A.; Francis, Isaac R.

    2013-01-01

    Abstract Several uncommon primary pancreatic tumors, inflammatory conditions, metastasis to the pancreas and peripancreatic masses can mimic the appearance of pancreatic ductal adenocarcinoma (PDA). Differentiation between these lesions and PDA can be challenging, due to the overlap in imaging features; however, familiarity with their typical imaging features and clinical presentation may be helpful in their differentiation, as in some cases, invasive diagnostic tests or unnecessary surgery can be avoided. The different pathologies that can mimic PDA include inflammatory conditions such as the various forms of pancreatitis (chronic-focal mass-forming, autoimmune and groove pancreatitis), pancreatic neuroendocrine tumors, solid pseudopapillary tumors, metastasis (solid non-lymphomatous and hematologic), congenital variants (annular pancreas), as well as peripancreatic lesions (accessory spleen, adrenal masses, duodenal masses, lymph nodes and vascular lesions), and certain rare pancreatic tumors (e.g., acinar cell tumors, solid serous tumors, hamartoma and solitary fibrous tumors). The clinical presentation and imaging features of the most commonly encountered mimics of PDA are discussed in this presentation with representative illustrations. PMID:24060833

  6. Histamine regulation of pancreatitis and pancreatic cancer: a review of recent findings

    PubMed Central

    Francis, Taylor; Graf, Allyson; Hodges, Kyle; Kennedy, Lindsey; Hargrove, Laura; Price, Mattie; Kearney, Kate

    2013-01-01

    The pancreas is a dynamic organ that performs a multitude of functions within the body. Diseases that target the pancreas, like pancreatitis and pancreatic cancer, are devastating and often fatal to the suffering patient. Histamine and histamine receptors (H1-H4HRs) have been found to play a critical role in biliary diseases. Accordingly, the biliary tract and the pancreas share similarities with regards to morphological, phenotypical and functional features and disease progression, studies related the role of H1-H4HRs in pancreatic diseases are important. In this review, we have highlighted the role that histamine, histidine decarboxylase (HDC), histamine receptors and mast cells (the main source of histamine in the body) play during both pancreatitis and pancreatic cancer. The objective of the review is to demonstrate that histamine and histamine signaling may be a potential therapeutic avenue towards treatment strategies for pancreatic diseases. PMID:24570946

  7. [DELAYED RESULTS OF ENZYME REPLACEMENT THERAPY, PRESCRIBED BY RESULTS OF 13C-TRIGLYCERIDE BREATH TEST].

    PubMed

    Chernyavskiy, V V; Gvozdetska, L S

    2015-01-01

    Maldigestion persists in most patients with chronic pancreatitis (CP). The objective lipase and amylase insufficiency diagnosis is needed to achieve an adequate clinical response to oral pancreatic enzyme substitution therapy. The novel data is presented in the article about the role of 13C-mixed triglyceride breath test as a tool for exocrine pancreatic insufficiency diagnosis, for evaluating fat malabsorbtion in CP patients. 135 patients were included in the investigation. Delayed results of enzyme replacement therapy were estimated after 1 and 2 year of surveillance. It has been shown, that partial recovery of exocrine pancreatic function is possible, and replacement therapy leads to patients nutritional status improving. Thus 13C-triglyceride breath test could be useful tool in clinical practice for CP diagnosis. The test make it possible to choose the initial pancreatic enzyme dosage and are beneficial during the treatment for pancreatic enzyme dose correction. PMID:26827447

  8. Reconstruction after pancreatic trauma by pancreaticogastrostomy

    PubMed Central

    Martín, Gonzalo Martín; Morillas, Patricia Jiménez; Pino, José C. Rodríguez; Canis, José M. Morón; Argenté, Francesc X. González

    2015-01-01

    Introduction Pancreatic lesions are very infrequent after closed abdominal trauma (5% of cases) with a complication rate that affects 30–40% of patients, and a mortality rate that can reach 39%. In our experience, closed abdominal traumatisms occurring at typical popular horse-riding festivals in our region constitute a high risk of pancreatic trauma. The purpose of the present paper is to raise awareness about our experience in the diagnosis and treatment of pancreatic lesions secondary to closed abdominal traumatism. Presentation of case We present the clinical cases of two young patients who, after suffering blunt abdominal trauma secondary to the impact of a horse during the celebration of typical horse-riding festival, were diagnosed with pancreatic trauma type III. The treatment was surgical in both cases and consisted in performing a pancreaticogastric anastomosis with preservation of the distal pancreas and spleen. The postoperative period was uneventful and, at present, both patients are asymptomatic. Discussion Signs and symptoms caused by pancreatic lesion are unspecific and difficult to objectify. With some limitations CT is the imaging test of choice for diagnosis and staging in the acute phase. The Wirsung section is indication for surgical treatment. The most extended surgical procedure in these cases is the resection of pancreatic body, tail, and spleen. Conclusion The identification of a pancreatic injury after closed abdominal trauma requires a high suspicion based on the injury mechanism. A safer option may be the distal pancreatic preservation with pancreaticogastric anastomosis in grade III lesions with healthy pancreatic tissue. PMID:25744560

  9. Autoimmune pancreatitis can develop into chronic pancreatitis

    PubMed Central

    2014-01-01

    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung’s and Santorini’s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922

  10. Antibiosis of Necrotizing Pancreatitis

    PubMed Central

    Arlt, Alexander; Erhart, Wiebke; Schafmayer, Clemens; Held, Hanns-Christoph; Hampe, Jochen

    2014-01-01

    Summary Background Necrotizing pancreatitis is a life-threatening presentation of acute pancreatitis. The mortality of 20-80% initially depends on the persistence of organ failure and systemic inflammatory response syndrome (SIRS) and, in the later course of the disease, on secondary infection of the necrosis. The questions whether prophylactic antibiotics aiming to prevent this infection should be administered and which antibiotic is the best to use, as well as the problem of fungal infection under antibiotic treatment are still intriguing and insufficiently solved. Methods A search of the literature using PubMed was carried out, supplemented by a review of the programmes of the Digestive Disease Week (DDW) and the United European Gastroenterology Week (UEGW). Results Despite the widely practised prophylactic antibiotic administration in severe pancreatitis, no evidence for the benefit of this strategy exists. One of the drawbacks might be a tendency for disastrous fungal infection under prophylactic antibiotics. Bacterial translocation from the gut in the second week after the onset of symptoms is the major source for infection of pancreatic necrosis and provides a clear indication for antibiotic treatment. However, routine fine-needle aspiration for a calculated antibiotic therapy cannot be recommended, and all other tests offer only indirect signs. Important factors such as enteral versus parenteral feeding and the method of necrosectomy are mostly neglected in the trials but seem to be essential for the outcome of the patient. Conclusions Even though most meta-analyses including the newer double-blind, placebo-controlled trials on prophylactic antibiotics showed no beneficial effects in the prevention of infection of necrosis and/or outcome of the patients, this strategy is still widely used in clinical routine. Since nearly all trials published so far show systematic problems (i.e. inaccurate definition of the severity of the disease, poor statistical testing

  11. Circulating Levels of Betatrophin and Irisin Are Not Associated with Pancreatic β-Cell Function in Previously Diagnosed Type 2 Diabetes Mellitus Patients

    PubMed Central

    Wang, Lingshu; Song, Jun; Wang, Chuan; Lin, Peng; Liang, Kai; Sun, Yu; He, Tianyi; Li, Wenjuan; Zhao, Ruxing; Qin, Jun; Lu, Yiran; Liu, Jinbo; Liu, Fuqiang; Hou, Xinguo; Chen, Li

    2016-01-01

    Betatrophin and irisin are two recently identified hormones which may participate in regulating pancreatic β-cell function. However, the associations of these two hormones with β-cell function remain unclear. The present study aims to demonstrate the associations of circulating betatrophin and irisin levels with β-cell function, assessed by the area under the curve (AUC) of C-peptide, and the possible correlation between these two hormones in previously diagnosed type 2 diabetes mellitus (T2DM) patients. In total, 20 age-, sex-, and body mass index- (BMI-) matched normal glucose tolerance (NGT) subjects and 120 previously diagnosed T2DM patients were included in this study. Partial correlation analysis was used to evaluate the relationships between these two hormones and indexes of β-cell function and insulin resistance. Our results showed that betatrophin levels were significantly elevated, while irisin levels were significantly decreased, in patients with T2DM compared with NGT subjects. However, partial correlation analysis showed that betatrophin levels did not correlate with β-cell function-related variables or insulin resistance-related variables before or after controlling multiple covariates, while irisin correlated positively with insulin sensitivity but is not associated with β-cell function-related variables. Besides, no correlation was observed between betatrophin and irisin levels. Hence we concluded that betatrophin and irisin were not associated with β-cell function in previously diagnosed T2DM patients. PMID:26649318

  12. Arachidonic acid actions on functional integrity and attenuation of the negative effects of palmitic acid in a clonal pancreatic β-cell line

    PubMed Central

    Keane, Deirdre C.; Takahashi, Hilton K.; Dhayal, Shalinee; Morgan, Noel G.; Curi, Rui; Newsholme, Philip

    2010-01-01

    Chronic exposure of pancreatic β-cells to saturated non-esterified fatty acids can lead to inhibition of insulin secretion and apoptosis. Several previous studies have demonstrated that saturated fatty acids such as PA (palmitic acid) are detrimental to β-cell function compared with unsaturated fatty acids. In the present study, we describe the effect of the polyunsaturated AA (arachidonic acid) on the function of the clonal pancreatic β-cell line BRIN-BD11 and demonstrate AA-dependent attenuation of PA effects. When added to β-cell incubations at 100 μM, AA can stimulate cell proliferation and chronic (24 h) basal insulin secretion. Microarray analysis and/or real-time PCR indicated significant AA-dependent up-regulation of genes involved in proliferation and fatty acid metabolism [e.g. Angptl (angiopoietin-like protein 4), Ech1 (peroxisomal Δ3,5,Δ2,4-dienoyl-CoA isomerase), Cox-1 (cyclo-oxygenase-1) and Cox-2, P<0.05]. Experiments using specific COX and LOX (lipoxygenase) inhibitors demonstrated the importance of COX-1 activity for acute (20 min) stimulation of insulin secretion, suggesting that AA metabolites may be responsible for the insulinotropic effects. Moreover, concomitant incubation of AA with PA dose-dependently attenuated the detrimental effects of the saturated fatty acid, so reducing apoptosis and decreasing parameters of oxidative stress [ROS (reactive oxygen species) and NO levels] while improving the GSH/GSSG ratio. AA decreased the protein expression of iNOS (inducible NO synthase), the p65 subunit of NF-κB (nuclear factor κB) and the p47 subunit of NADPH oxidase in PA-treated cells. These findings indicate that AA has an important regulatory and protective β-cell action, which may be beneficial to function and survival in the ‘lipotoxic’ environment commonly associated with Type 2 diabetes mellitus. PMID:20840078

  13. Association between the rs4753426 polymorphism in MTNR1B with fasting plasma glucose level and pancreatic β-cell function in gestational diabetes mellitus.

    PubMed

    Zhan, Y; Li, C; Gao, Q; Chen, J; Yu, S; Liu, S G

    2015-01-01

    We investigated the association between rs4753426 single nucleotide polymorphisms in the melatonin receptor 1B (MTNR1B) gene and the risk of developing gestational diabetes mellitus (GDM). A total of 516 gravidas (186 with GDM and 330 non-diabetic controls) were enrolled in the study. Genotype and allele frequencies of rs4753426 in the MTNR1B gene were detected by DNA sequencing. Fasting plasma glucose and fasting insulin levels were measured to calculate the homeostasis model assessment for insulin resistance (HOMA-IR) and for β-cell function. Three genotypes (CC, CT, and TT) were found in both groups. The frequencies of CC, CT, and TT genotypes for the GDM group were 70.97, 22.58, and 6.45% vs 53.03, 39.70, and 7.27% in the control group, respectively. Significant differences were observed in genotype frequencies between groups (P < 0.05). T and C allele frequencies in the GDM group were 17.74 and 82.26%, respectively, and in the control group were 27.12 and 72.88%, respectively. Significant differences in T and C allele frequencies were found between groups (P < 0.05). In the GDM group, the C allele was associated with increased fasting plasma glucose level and reduced pancreatic β-cell function (P < 0.05). There were no significant differences in total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein concentration, or HOMA-IR between groups (P > 0.05). The single nucleotide polymorphism rs4753426 in MTNR1B may be a susceptibility gene locus for GDM, and the C allele may contribute to the increased fasting plasma glucose level and reduced pancreatic β-cell function. PMID:26345809

  14. A Comparison of Statistical Significance Tests for Selecting Equating Functions

    ERIC Educational Resources Information Center

    Moses, Tim

    2009-01-01

    This study compared the accuracies of nine previously proposed statistical significance tests for selecting identity, linear, and equipercentile equating functions in an equivalent groups equating design. The strategies included likelihood ratio tests for the loglinear models of tests' frequency distributions, regression tests, Kolmogorov-Smirnov…

  15. Chronic Pancreatitis and Pancreatic Cancer

    PubMed Central

    Kong, Xiangyu; Sun, Tao; Kong, Fanyang; Du, Yiqi; Li, Zhaoshen

    2014-01-01

    Background Pancreatic cancer (PC) is one of the most lethal diseases with an incidence rate almost equal to the rate of mortality. Chronic pancreatitis (CP) is a common chronic inflammatory disease of unknown etiology that affects the pancreas. Epidemiological studies have identified CP to be a major risk factor for PC. Summary A greater understanding of the molecular mechanisms linking CP and PC has identified several common pathways that provide targets for future interventions. This article reviews those components in the CP-PC connection, including the role of macrophages, the maintenance of genome stability, cytokines, and other nodal factors such as nuclear factor kappa B, COX-2 and reactive oxygen species. Key Message The molecular mechanisms that underlie CP and PC provide novel targets for future therapies for PC. Practical Implications The stromal-desmoplastic reaction plays an important role in initiating and sustaining chronic inflammation and tumor progression. Recently, two targeted anti-tumor agents, erlotinib and nab-paclitaxel, have shown promising therapeutic efficacy. Notably, both these agents target components (EGFR and SPARC) within the inflammatory stroma surrounding malignant cells, underscoring the importance of inflammation in pancreatic carcinogenesis. Identifying the common pathways linking CP and PC may help uncover additional novel targets for future therapies. PMID:26674754

  16. Autoimmune Pancreatitis - A Riddle Wrapped in an Enigma.

    PubMed

    Webster, George J

    2016-01-01

    Autoimmune pancreatitis (AIP) was recognized as a clinical entity, at least in the West little more than 10 years ago. Since then, studies globally, and international collaboration, have led to important advances in our understanding of its clinical features, disease course, and management, although the aetiopathogenesis of this curious disease remains to be fully elucidated. Types 1 and 2 AIP have been described, of which type 1 is the commonest form, and best defined. International consensus now recognizes it as one of the many clinical manifestations of IgG4-related disease, and is now termed IgG4-related pancreatitis (IgG4-RP). The disease is not confined to a particular race, gender, or age, but often presents after the fifth decade in men. A common presentation is with jaundice due to low bile duct obstruction related to diffuse pancreatic enlargement (historically often leading to a misdiagnosis of cancer). Acute pancreatitis is unusual. Other organ involvement is a particular feature, including biliary disease, retroperitoneal fibrosis, generalized lymphadenopathy, renal, and lung involvement. No single test makes the diagnosis, and diagnostic criteria for type 1 AIP/IgG4-RP, which incorporate clinical, laboratory, radiological, pathological, and therapeutic parameters should be applied. A particular attempt should be made to make a histological diagnosis, which is characterized by an IgG4-positive lymphoplasmacytic infiltrate. Management is not based on randomized studies, but corticosteroids are the mainstay of treatment, providing rapid clinical and radiological benefit. However, clinical relapse is common (particularly in type 1 AIP, and in those with associated other organ involvement). Additional immunosuppression may be required, including azathioprine, and rituximab may play an emerging role. The disease course is variable, but loss of organ function (especially pancreatic exocrine failure and pancreatic atrophy) may occur. PMID:27333053

  17. Insulin exerts metabolic and growth-promoting effects by a direct action on the liver in vivo: clarification of the functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver.

    PubMed Central

    Griffen, S C; Russell, S M; Katz, L S; Nicoll, C S

    1987-01-01

    The functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver has not been established. Previous studies indicated that insulin does not acutely regulate glucose metabolism by a direct hepatic effect. More recent observations suggest that the role of insulin in regulating body growth may be mediated, at least in part, by the liver. Our experiments were designed to test whether insulin can promote body growth and regulate glucose metabolism by a direct hepatic action in vivo. Rats were made diabetic by injections of streptozotocin, and insulin or solvent was infused into the jugular vein (JV) or the hepatic portal vein (HPV) for 14 days using catheters that were attached to osmotic minipumps. Infusion of a low dose of insulin (2 units per kg per day) into the JV had no effects on the hyperglycemia, body weight gain, tail growth, tibial epiphysial cartilage plate thickness, or serum levels of somatomedin C in the diabetic rats. However, the same dose given into the HPV caused a 30% reduction of blood glucose and stimulated a significant degree of growth, as determined by all indices. Infusion of a higher dose of insulin (5 units per kg per day) into either vein caused full restoration of body weight gain and tail growth and it restored the glycemic status almost to normal. However, it did not increase the tibial epiphysial plate width or serum somatomedin C levels above those of the rats given the low dose of the hormone into the HPV. These results indicate that insulin can act directly on the liver to promote body growth and to regulate glucose metabolism. The significance of direct delivery of insulin from the pancreatic beta cells to the liver may be as much for growth control as for glucose homeostasis. Images PMID:3313390

  18. Effectiveness of plasma treatment on pancreatic cancer cells

    PubMed Central

    HATTORI, NORIFUMI; YAMADA, SUGURU; TORII, KOJI; TAKEDA, SHIGEOMI; NAKAMURA, KAE; TANAKA, HIROMASA; KAJIYAMA, HIROAKI; KANDA, MITSURO; FUJII, TSUTOMU; NAKAYAMA, GORO; SUGIMOTO, HIROYUKI; KOIKE, MASAHIKO; NOMOTO, SHUJI; FUJIWARA, MICHITAKA; MIZUNO, MASAAKI; HORI, MASARU; KODERA, YASUHIRO

    2015-01-01

    Non-equilibrium atmospheric pressure plasma (NEAPP) has attracted attention in cancer therapy. We explored the indirect effect of NEAPP through plasma-activated medium (PAM) on pancreatic cancer cells in vitro and in vivo. In this study, four pancreatic cancer cell lines were used and the antitumor effects of PAM treatment were evaluated using a cell proliferation assay. To explore functional mechanisms, morphological change and caspase-3/7 activation in cells were also assessed. Furthermore, reactive oxygen species (ROS) generation in cells was examined and N-acetyl cysteine (NAC), an intracellular ROS scavenger, was tested. Finally, the antitumor effect of local injection of PAM was investigated in a mouse xenograft model. We found that PAM treatment had lethal effect on pancreatic cancer cells. Typical morphological findings suggestive of apoptosis such as vacuolization of cell membranes, small and round cells and aggregation of cell nuclei, were observed in the PAM treated cells. Caspase-3/7 activation was detected in accordance with the observed morphological changes. Additionally, ROS uptake was observed in all cell lines tested, while the antitumor effects of PAM were completely inhibited with NAC. In the mouse xenograft model, the calculated tumor volume on day 28 in the PAM treatment group was significantly smaller compared with the control group [28±22 vs. 89±38 (mm3 ± SD), p=0.0031]. These results show that PAM treatment of pancreatic cancer might be a promising therapeutic strategy. PMID:26351772

  19. Axial force measurement for esophageal function testing.

    PubMed

    Gravesen, Flemming H; Funch-Jensen, Peter; Gregersen, Hans; Drewes, Asbjørn Mohr

    2009-01-14

    The esophagus serves to transport food and fluid from the pharynx to the stomach. Manometry has been the "golden standard" for the diagnosis of esophageal motility diseases for many decades. Hence, esophageal function is normally evaluated by means of manometry even though it reflects the squeeze force (force in radial direction) whereas the bolus moves along the length of esophagus in a distal direction. Force measurements in the longitudinal (axial) direction provide a more direct measure of esophageal transport function. The technique used to record axial force has developed from external force transducers over in-vivo strain gauges of various sizes to electrical impedance based measurements. The amplitude and duration of the axial force has been shown to be as reliable as manometry. Normal, as well as abnormal, manometric recordings occur with normal bolus transit, which have been documented using imaging modalities such as radiography and scintigraphy. This inconsistency using manometry has also been documented by axial force recordings. This underlines the lack of information when diagnostics are based on manometry alone. Increasing the volume of a bag mounted on a probe with combined axial force and manometry recordings showed that axial force amplitude increased by 130% in contrast to an increase of 30% using manometry. Using axial force in combination with manometry provides a more complete picture of esophageal motility, and the current paper outlines the advantages of using this method. PMID:19132762

  20. Testing the functional significance of tail streamers

    PubMed Central

    Evans, M. R.; Thomas, A. L. R.

    1997-01-01

    Studies of the evolution of elaborate ornaments have concentrated on their role in increasing attractiveness to mates. The classic examples of such sexually selected structures are the elongated tails of some bird species. Elongated tails can be divided into three categories: graduated tails, pin tails and streamers. There seems to be little debate about whether graduated and pin tails are ornaments; i.e. costly signals used in mate choice. However, in the case of streamers there is considerable discussion about their function. It has been suggested that tail streamers could be (i) entirely naturally selected, (ii) entirely sexually selected, (iii) partly naturally and partly sexually selected. The prime example of a species with tail streamers is the swallow (Hirundo rustica) in which both sexes have tail streamers. In this paper we discuss the aerodynamic consequences of different types of manipulation of the streamer and/or outer tail feather. We make qualitative predictions about the aerodynamic performance of swallows with manipulated tail streamers; these predictions differ depending on whether streamers have a naturally or sexually selected function. We demonstrate that these hypotheses can only be separated if tail streamers are shortened and changes in aerodynamic performance measured during turning flight.

  1. Animal models for investigating chronic pancreatitis

    PubMed Central

    2011-01-01

    Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed. PMID:22133269

  2. Animal models for investigating chronic pancreatitis.

    PubMed

    Aghdassi, Alexander A; Mayerle, Julia; Christochowitz, Sandra; Weiss, Frank U; Sendler, Matthias; Lerch, Markus M

    2011-01-01

    Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed. PMID:22133269

  3. Association of variants in genes involved in pancreatic β-cell development and function with type 2 diabetes in North Indians.

    PubMed

    Chavali, Sreenivas; Mahajan, Anubha; Tabassum, Rubina; Dwivedi, Om Prakash; Chauhan, Ganesh; Ghosh, Saurabh; Tandon, Nikhil; Bharadwaj, Dwaipayan

    2011-10-01

    Variants in genes involved in pancreatic β-cell development and function are known to cause monogenic forms of type 2 diabetes and are also associated with complex form. In this study, we studied the genetic association of polymorphisms in such important genes with type 2 diabetes in the high-risk Indians. We genotyped 91 polymorphisms in 19 genes (ABCC8, HNF1A, HNF1B, HNF4A, INS, INSM1, ISL1, KCNJ11, MAFA, MNX1, NEUROD1, NEUROG3, NKX2.2, NKX6.1, PAX4, PAX6, PDX1, USF1 and WFS1) in 2025 unrelated North Indians of Indo-European ethnicity comprising of 1019 diabetic and 1006 non-diabetic subjects. HNF4A promoter P2 polymorphisms rs1884613 and rs2144908, which are in high linkage disequilibrium, showed significant association with type 2 diabetes (odds ratio (OR)=1.37 (95% confidence interval (CI) 1.19-1.57), P=9.4 × 10(-6) for rs1884613 and OR=1.37 (95%CI 1.20-1.57), P=6.0 × 10(-6) for rs2144908), as previously shown in other populations. We observed body mass index-dependent association of these variants with type 2 diabetes in normal-weight/lean subjects. Variants in USF1, ABCC8, ISL1 and KCNJ11 showed nominal association, while haplotypes in these genes were significantly associated. rs3812704 upstream of NEUROG3 significantly increased risk for type 2 diabetes in normal-weight/lean subjects (OR=1.68 (95%CI 1.25-2.24), P=4.9 × 10(-4)). Thus, pancreatic β-cell development and function genes contribute to susceptibility to type 2 diabetes in North Indians. PMID:21814221

  4. Therapeutic targeting of the Warburg effect in pancreatic cancer relies on an absence of p53 function

    PubMed Central

    Rajeshkumar, N.V.; Dutta, Prasanta; Yabuuchi, Shinichi; de Wilde, Roeland F.; Matrinez, Gary V.; Le, Anne; Kamphorst, Jurre J.; Rabinowitz, Josh D.; Jain, Sanjay K.; Hidalgo, Manuel; Dang, Chi V.; Gillies, Robert J.; Maitra, Anirban

    2015-01-01

    The “Warburg effect” describes a peculiar metabolic feature of many solid tumors, namely their high glycolytic activity for biosynthesis and an inefficient generation of ATP. During aerobic glycolysis, pyruvate is preferentially metabolized to lactate by the enzyme lactate dehydrogenase-A (LDH-A), suggesting a possible vulnerability at this target for small molecule inhibition in cancer cells. In this study, we used FX11, a small molecule inhibitor of LDH-A, to investigate this possible vulnerability in a panel of 15 patient-derived mouse xenograft (PDX) models of pancreatic cancer. Unexpectedly, the p53 status of the PDX tumor determined the response to FX11. Tumors harboring wild-type (WT) TP53 were completely resistant to FX11. In contrast, tumors harboring mutant TP53 exhibited increased apoptosis, reduced proliferation indices and attenuated tumor growth when exposed to FX11. [18F]-FDG PET-CT scans revealed a relative increase in glucose uptake in mutant TP53 versus WT TP53 tumors, with FX11 administration downregulating metabolic activity only in mutant TP53 tumors. Through a non-invasive quantitative assessment of lactate production, as determined by 13C magnetic resonance spectroscopy (MRS) of hyperpolarized pyruvate, we confirmed that FX11 administration inhibited pyruvate-to-lactate conversion only in mutant TP53 tumors, a feature associated with reduced expression of the TP53 target gene TIGAR, which is known to regulate glycolysis. Taken together, our findings highlight p53 status in pancreatic cancer as biomarker to predict sensitivity to LDH-A inhibition, with regard to both real-time non-invasive imaging by 13C MRS as well as therapeutic response. PMID:26113084

  5. Significance tests for functional data with complex dependence structure

    PubMed Central

    Lahiri, Soumen N.; Carroll, Raymond J.

    2015-01-01

    We propose an L2-norm based global testing procedure for the null hypothesis that multiple group mean functions are equal, for functional data with complex dependence structure. Specifically, we consider the setting of functional data with a multilevel structure of the form groups–clusters or subjects–units, where the unit-level profiles are spatially correlated within the cluster, and the cluster-level data are independent. Orthogonal series expansions are used to approximate the group mean functions and the test statistic is estimated using the basis coefficients. The asymptotic null distribution of the test statistic is developed, under mild regularity conditions. To our knowledge this is the first work that studies hypothesis testing, when data have such complex multilevel functional and spatial structure. Two small-sample alternatives, including a novel block bootstrap for functional data, are proposed, and their performance is examined in simulation studies. The paper concludes with an illustration of a motivating experiment. PMID:26023253

  6. Coaching patients during pulmonary function testing: A practical guide.

    PubMed

    Cheung, Heidi J; Cheung, Lawrence

    2015-01-01

    Pulmonary function tests are an important tool to assist in the diagnosis and management of patients with respiratory disease. Ensuring that the tests are of acceptable quality is vital. Acceptable pulmonary function test quality requires, among others, optimal patient performance. Optimal patient performance, in turn, requires adequate coaching from registered respiratory therapists (RRTs) and other pulmonary function laboratory personnel. The present article provides techniques and tips to help RRTs coach patients during testing. The authors briefly review the components of pulmonary function testing, then describe factors that may hinder a patient's performance, list common mistakes that patients make during testing, and provide tips that RRTs can use to help patients optimize their performance. PMID:26283871

  7. Endoscopic diagnostic of chronic pancreatitis.

    PubMed

    Cubranić, Aleksandar; Dintinjana, Renata Dobrila; Vanis, Nenad

    2014-12-01

    Chronic pancreatitis is defined as a continuous inflammatory pancreatic disease, one characterized by irreversible morphological changes, often associates with pain and sometimes with the loss of endocrine and exocrine function. As a histological confirmation of chronic pancreatitis is often unavailable, the diagnosis is traditionally based on imaging methods such as computerized tomography (CT) or endoscopic retrograde cholangiopancreatography (ERCP), and recently magnetic resonance cholangiopancreatography (MRCP) as a noninvasive alternative to ERCP. Developments in the classification system of CP include the Marseille classification of 1963 which offered histopathologic criteria for CP, the Cambridge classification of 1984 which introduced imaging features of computed tomography (CT), transabdominal ultrasound (TUS) and endoscopic retrograde cholangiopancreatography (ERCP) for classification of CP as well as Rosemont classification system of 2007 which presented the endoscopic ultrasonography diagnosis of CP. Endoscopic ultra-sonography (EUS) was first introduced as a diagnostic method for evaluation of pancreatic disease in 1986. It has experienced significant improvements since then and allowed for an alternative approach in diagnosing patients with pancreatic diseases. In patients with suspected pancreatic masses EUS-guided fine needle aspiration (EUS-FNA) is the best method for obtaining tissue diagnosis and differentiating CP from pancreatic carcinoma. The recent studies indicate that EUS is the method of choice when compared with other imaging methods such as ERCP because it frequently provides more accurate diagnostics. The aim of this review is to discuss the findings in endoscopic diagnostics up to the present moment and to indicate advantages, limitations and possible complications along with the current recommendations in CP diagnostics. PMID:25842773

  8. Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional markers after acute pancreatitis

    PubMed Central

    Vujasinovic, Miroslav; Tepes, Bojan; Makuc, Jana; Rudolf, Sasa; Zaletel, Jelka; Vidmar, Tjasa; Seruga, Maja; Birsa, Bostjan

    2014-01-01

    AIM: To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis (AP). METHODS: Patients with AP were invited to participate in the study. Severity of AP was determined by the Atlanta classification and definitions revised in 2012. Pancreatic exocrine insufficiency (PEI) was diagnosed by the concentration of fecal elastase-1. An additional work-up, including laboratory testing of serum nutritional markers for determination of malnutrition, was offered to all patients with low levels of fecal elastase-1 FE. Hemoglobin A1c or oral glucose tolerance tests were also performed in patients without prior diabetes mellitus, and type 3c diabetes mellitus (T3cDM) was diagnosed according to American Diabetes Association criteria. RESULTS: One hundred patients were included in the study: 75% (75/100) of patients had one attack of AP and 25% (25/100) had two or more attacks. The most common etiology was alcohol. Mild, moderately severe and severe AP were present in 67, 15 and 18% of patients, respectively. The mean time from attack of AP to inclusion in the study was 2.7 years. PEI was diagnosed in 21% (21/100) of patients and T3cDM in 14% (14/100) of patients. In all patients with PEI, at least one serologic nutritional marker was below the lower limit of normal. T3cDM was more frequently present in patients with severe AP (P = 0.031), but was also present in some patients with mild and moderately severe AP. PEI was present in all degrees of severity of AP. There were no statistically significantly differences according to gender, etiology and number of AP attacks. CONCLUSION: As exocrine and endocrine pancreatic insufficiency can develop after AP, routine follow-up of patients is necessary, for which serum nutritional panel measurements can be useful. PMID:25561813

  9. Loss of acinar cell IKKα triggers spontaneous pancreatitis in mice

    PubMed Central

    Li, Ning; Wu, Xuefeng; Holzer, Ryan G.; Lee, Jun-Hee; Todoric, Jelena; Park, Eek-Joong; Ogata, Hisanobu; Gukovskaya, Anna S.; Gukovsky, Ilya; Pizzo, Donald P.; VandenBerg, Scott; Tarin, David; Atay, Çiǧdem; Arkan, Melek C.; Deerinck, Thomas J.; Moscat, Jorge; Diaz-Meco, Maria; Dawson, David; Erkan, Mert; Kleeff, Jörg; Karin, Michael

    2013-01-01

    Chronic pancreatitis is an inflammatory disease that causes progressive destruction of pancreatic acinar cells and, ultimately, loss of pancreatic function. We investigated the role of IκB kinase α (IKKα) in pancreatic homeostasis. Pancreas-specific ablation of IKKα (IkkαΔpan) caused spontaneous and progressive acinar cell vacuolization and death, interstitial fibrosis, inflammation, and circulatory release of pancreatic enzymes, clinical signs resembling those of human chronic pancreatitis. Loss of pancreatic IKKα causes defective autophagic protein degradation, leading to accumulation of p62-mediated protein aggregates and enhanced oxidative and ER stress in acinar cells, but none of these effects is related to NF-κB. Pancreas-specific p62 ablation prevented ER and oxidative stresses and attenuated pancreatitis in IkkαΔpan mice, suggesting that cellular stress induced by p62 aggregates promotes development of pancreatitis. Importantly, downregulation of IKKα and accumulation of p62 aggregates were also observed in chronic human pancreatitis. Our studies demonstrate that IKKα, which may control autophagic protein degradation through its interaction with ATG16L2, plays a critical role in maintaining pancreatic acinar cell homeostasis, whose dysregulation promotes pancreatitis through p62 aggregate accumulation. PMID:23563314

  10. Memory Hazard Functions: A Vehicle for Theory Development and Test

    ERIC Educational Resources Information Center

    Chechile, Richard A.

    2006-01-01

    A framework is developed to rigorously test an entire class of memory retention functions by examining hazard properties. Evidence is provided that the memory hazard function is not monotonically decreasing. Yet most of the proposals for retention functions, which have emerged from the psychological literature, imply that memory hazard is…

  11. A Generalized DIF Effect Variance Estimator for Measuring Unsigned Differential Test Functioning in Mixed Format Tests

    ERIC Educational Resources Information Center

    Penfield, Randall D.; Algina, James

    2006-01-01

    One approach to measuring unsigned differential test functioning is to estimate the variance of the differential item functioning (DIF) effect across the items of the test. This article proposes two estimators of the DIF effect variance for tests containing dichotomous and polytomous items. The proposed estimators are direct extensions of the…

  12. Effect of Multiple Testing Adjustment in Differential Item Functioning Detection

    ERIC Educational Resources Information Center

    Kim, Jihye; Oshima, T. C.

    2013-01-01

    In a typical differential item functioning (DIF) analysis, a significance test is conducted for each item. As a test consists of multiple items, such multiple testing may increase the possibility of making a Type I error at least once. The goal of this study was to investigate how to control a Type I error rate and power using adjustment…

  13. Vertically integrated translational studies of PDX1 as a therapeutic target for pancreatic cancer via a novel bifunctional RNAi platform.

    PubMed

    Wu, J; Liu, S; Yu, J; Zhou, G; Rao, D; Jay, C M; Kumar, P; Sanchez, R; Templeton, N; Senzer, N; Maples, P; Nemunaitis, J; Brunicardi, F C

    2014-02-01

    RNA interference (RNAi) represents a powerful, new tool for scientific investigation as well as a promising new form of targeted gene therapy, with applications currently in clinical trials. Bifunctional short hairpin RNA (shRNA) are synthetic RNAi molecules, engineered to utilize multiple endogenous RNAi pathways to specifically silence target genes. Pancreatic and duodenal homeobox 1 (PDX1) is a key regulator of pancreatic development, β-cell differentiation, normal β-cell function and pancreatic cancer. Our aim is to review the process of identifying PDX1 as a specific, potential RNAi target in pancreatic cancer, as well as the underlying mechanisms and various forms of RNAi, with subsequent testing and development of PDX1-targeted bifunctional shRNA therapy. PMID:24457987

  14. A physiological pattern of oxygenation using perfluorocarbon-based culture devices maximizes pancreatic islet viability and enhances β-cell function.

    PubMed

    Fraker, Chris A; Cechin, Sirlene; Álvarez-Cubela, Silvia; Echeverri, Felipe; Bernal, Andrés; Poo, Ramón; Ricordi, Camillo; Inverardi, Luca; Domínguez-Bendala, Juan

    2013-01-01

    Conventional culture vessels are not designed for physiological oxygen (O2) delivery. Both hyperoxia and hypoxia-commonly observed when culturing cells in regular plasticware-have been linked to reduced cellular function and death. Pancreatic islets, used for the clinical treatment of diabetes, are especially sensitive to sub- and supraphysiological O2 concentrations. A result of current culture standards is that a high percentage of islet preparations are never transplanted because of cell death and loss of function in the 24-48 h postisolation. Here, we describe a new culture system designed to provide quasiphysiological oxygenation to islets in culture. The use of dishes where islets rest atop a perfluorocarbon (PFC)-based membrane, coupled with a careful adjustment of environmental O2 concentration to target the islet physiological pO2 range, resulted in dramatic gains in viability and function. These observations underline the importance of approximating culture conditions as closely as possible to those of the native microenvironment, and fill a widely acknowledged gap in our ability to preserve islet functionality in vitro. As stem cell-derived insulin-producing cells are likely to suffer from the same limitations as those observed in real islets, our findings are especially timely in the context of current efforts to define renewable sources for transplantation. PMID:23068091

  15. Primary Cilia in Pancreatic Development and Disease

    PubMed Central

    Lodh, Sukanya; O’Hare, Elizabeth A.; Zaghloul, Norann A.

    2014-01-01

    Primary cilia and their anchoring basal bodies are important regulators of a growing list of signaling pathways. Consequently, dysfunction in proteins associated with these structures results in perturbation of the development and function of a spectrum of tissue and cell types. Here, we review the role of cilia in mediating the development and function of the pancreas. We focus on ciliary regulation of major pathways involved in pancreatic development, including Shh, Wnt, TGF-β, Notch, and fibroblast growth factor. We also discuss pancreatic phenotypes associated with ciliary dysfunction, including pancreatic cysts and defects in glucose homeostasis, and explore the potential role of cilia in such defects. PMID:24864023

  16. A Novel Function of Noc2 in Agonist-Induced Intracellular Ca2+ Increase during Zymogen-Granule Exocytosis in Pancreatic Acinar Cells

    PubMed Central

    Ogata, Sho; Miki, Takashi; Seino, Susumu; Tamai, Seiichi; Kasai, Haruo; Nemoto, Tomomi

    2012-01-01

    Noc2, a putative Rab effector, contributes to secretory-granule exocytosis in neuroendocrine and exocrine cells. Here, using two-photon excitation live-cell imaging, we investigated its role in Ca2+-dependent zymogen granule (ZG) exocytosis in pancreatic acinar cells from wild-type (WT) and Noc2-knockout (KO) mice. Imaging of a KO acinar cell revealed an expanded granular area, indicating ZG accumulation. In our spatiotemporal analysis of the ZG exocytosis induced by agonist (cholecystokinin or acetylcholine) stimulation, the location and rate of progress of ZG exocytosis did not differ significantly between the two strains. ZG exocytosis from KO acinar cells was seldom observed at physiological concentrations of agonists, but was normal (vs. WT) at high concentrations. Flash photolysis of a caged calcium compound confirmed the integrity of the fusion step of ZG exocytosis in KO acinar cells. The decreased ZG exocytosis present at physiological concentrations of agonists raised the possibility of impaired elicitation of calcium spikes. When calcium spikes were evoked in KO acinar cells by a high agonist concentration: (a) they always started at the apical portion and traveled to the basal portion, and (b) calcium oscillations over the 10 µM level were observed, as in WT acinar cells. At physiological concentrations of agonists, however, sufficient calcium spikes were not observed, suggesting an impaired [Ca2+]i-increase mechanism in KO acinar cells. We propose that in pancreatic acinar cells, Noc2 is not indispensable for the membrane fusion of ZG per se, but instead performs a novel function favoring agonist-induced physiological [Ca2+]i increases. PMID:22615885

  17. MicroRNA-206 functions as a pleiotropic modulator of cell proliferation, invasion and lymphangiogenesis in pancreatic adenocarcinoma by targeting ANXA2 and KRAS genes.

    PubMed

    Keklikoglou, I; Hosaka, K; Bender, C; Bott, A; Koerner, C; Mitra, D; Will, R; Woerner, A; Muenstermann, E; Wilhelm, H; Cao, Y; Wiemann, S

    2015-09-10

    Recent advances in cancer biology have emerged important roles for microRNAs (miRNAs) in regulating tumor responses. However, their function in mediating intercellular communication within the tumor microenvironment is thus far poorly explored. Here, we found miR-206 to be abrogated in human pancreatic ductal adenocarcinoma (PDAC) specimens and cell lines. We show that miR-206 directly targets the oncogenes KRAS and annexin a2 (ANXA2), thereby acting as tumor suppressor in PDAC cells by blocking cell cycle progression, cell proliferation, migration and invasion. Importantly, we identified miR-206 as a negative regulator of oncogenic KRAS-induced nuclear factor-κB transcriptional activity, resulting in a concomitant reduction of the expression and secretion of pro-angiogenic and pro-inflammatory factors including the cytokine interleukin-8, the chemokines (C-X-C motif) ligand 1 and (C-C motif) ligand 2, and the granulocyte macrophage colony-stimulating factor. We further show that miR-206 abrogates the expression and secretion of the potent pro-lymphangiogenic factor vascular endothelial growth factor C in pancreatic cancer cells through an NF-κB-independent mechanism. By using in vitro and in vivo approaches, we reveal that re-expression of miR-206 in PDAC cells is sufficient to inhibit tumor blood and lymphatic vessel formation, thus leading to a significant delay of tumor growth and progression. Taken together, our study sheds light onto the role of miR-206 as a pleiotropic modulator of different hallmarks of cancer, and as such raising the intriguing possibility that miR-206 may be an attractive candidate for miRNA-based anticancer therapies. PMID:25500542

  18. A novel function of Noc2 in agonist-induced intracellular Ca2+ increase during zymogen-granule exocytosis in pancreatic acinar cells.

    PubMed

    Ogata, Sho; Miki, Takashi; Seino, Susumu; Tamai, Seiichi; Kasai, Haruo; Nemoto, Tomomi

    2012-01-01

    Noc2, a putative Rab effector, contributes to secretory-granule exocytosis in neuroendocrine and exocrine cells. Here, using two-photon excitation live-cell imaging, we investigated its role in Ca(2+)-dependent zymogen granule (ZG) exocytosis in pancreatic acinar cells from wild-type (WT) and Noc2-knockout (KO) mice. Imaging of a KO acinar cell revealed an expanded granular area, indicating ZG accumulation. In our spatiotemporal analysis of the ZG exocytosis induced by agonist (cholecystokinin or acetylcholine) stimulation, the location and rate of progress of ZG exocytosis did not differ significantly between the two strains. ZG exocytosis from KO acinar cells was seldom observed at physiological concentrations of agonists, but was normal (vs. WT) at high concentrations. Flash photolysis of a caged calcium compound confirmed the integrity of the fusion step of ZG exocytosis in KO acinar cells. The decreased ZG exocytosis present at physiological concentrations of agonists raised the possibility of impaired elicitation of calcium spikes. When calcium spikes were evoked in KO acinar cells by a high agonist concentration: (a) they always started at the apical portion and traveled to the basal portion, and (b) calcium oscillations over the 10 µM level were observed, as in WT acinar cells. At physiological concentrations of agonists, however, sufficient calcium spikes were not observed, suggesting an impaired [Ca(2+)](i)-increase mechanism in KO acinar cells. We propose that in pancreatic acinar cells, Noc2 is not indispensable for the membrane fusion of ZG per se, but instead performs a novel function favoring agonist-induced physiological [Ca(2+)](i) increases. PMID:22615885

  19. 2-Oxocarboxylic acids and function of pancreatic islets in obese–hyperglycaemic mice. Insulin secretion in relation to 45Ca uptake and metabolism

    PubMed Central

    Lenzen, Sigurd; Panten, Uwe

    1980-01-01

    The effects of aliphatic 2-oxocarboxylic acids, at concentrations of up to 40mm, on the function of pancreatic islets from ob/ob (obese–hyperglycaemic) mice were investigated. 1. 2-Oxopentanoate, dl-3-methyl-2-oxopentanoate, 4-methyl-2-oxopentanoate and 2-oxohexanoate all induced insulin release by isolated incubated islets and a biphasic insulin-secretory pattern in perfused mouse pancreas. The last two substances were similar in potency to glucose. Pyruvate, 2-oxobutyrate, 3-methyl-2-oxobutyrate and 2-oxo-octanoate did not induce insulin release significantly. 2. 2-Oxocarboxylic acids with significant insulin-secretory potency also induced significant 45Ca uptake by isolated incubated islets. 3. The rates of decarboxylation of [1-14C]pyruvate, 3-methyl-2-oxo[1-14C]butyrate and 4-methyl-2-oxo[1-14C]pentanoate were twice as high as the rates of oxidation of the corresponding U-14C-labelled compounds. However, whereas the rates of metabolism of labelled pyruvate and 3-methyl-2-oxobutyrate steadily increased over the concentration range 1–40mm, those of labelled 4-methyl-2-oxopentanoate and d-[U-14C]glucose levelled off at concentrations above 10mm. 4. Omission of 40CaCl2 from the incubation medium reduced the rate of oxidation of the insulin secretagogue [U-14C]4-methyl-2-oxopentanoate, but left that of the non-(insulin secretagogue) [U-14C]3-methyl-2-oxobutyrate unaffected. 5. Only glucose, and not pyruvate, 3-methyl-2-oxobutyrate and 4-methyl-2-oxopentanoate, significantly inhibited oxidation of endogenous fatty acids. 6. It is suggested that stimulus–secretion coupling and the resulting exocytosis of insulin in pancreatic β-cells may modulate both fuel oxidation and 45Ca uptake. PMID:6989358

  20. Alcohol abuse-related severe acute pancreatitis with rhabdomyolysis complications

    PubMed Central

    SU, MAO-SHENG; JIANG, YING; YAN, XIAO-YUAN HU; ZHAO, QING-HUA; LIU, ZHI-WEI; ZHANG, WEN-ZHI; HE, LEI

    2013-01-01

    Non-traumatic rhabdomyolysis is a rare complication of acute pancreatitis. One of the major risk factors of both acute pancreatitis and rhabdomyolysis is alcohol abuse. However, only a few studies have reported the prognosis and association of severe acute pancreatitis (SAP) and rhabdomyolysis in alcohol abuse patients. In the present study, we report two cases presenting with SAP complicated by rhabdomyolysis following high-dose alcohol intake. The disease onset, clinical manifestations, laboratory data, diagnosis and treatment procedure of each patient were recorded, and the association with rhabdomyolysis was analyzed. Alcohol consumption was the most predominant cause of SAP and rhabdomyolysis in these patients. SAP-related rhabdomyolysis was primarily induced by the toxicity associated with pancreatic necrosis. The laboratory tests revealed that the concentration of serum creatine kinase (CK) and myoglobin increased and acute renal failure symptoms were present, which provided an exact diagnosis for SAP-induced rhabdomyolysis. Rhabdomyolysis and subsequent hypermyoglobinuria severely impaired kidney function and aggravated hypocalcemia. The therapy of early stage SAP complicated by rhabdomyolysis involved liquid resuscitation support. When first stage treatment fails, blood purification should be performed immediately. Both patients developed multiple organ failure (MOF) and succumbed to the disease. Considering the two cases presented, we conclude that alcohol-related SAP complicated by rhabdomyolysis may have a poor clinical prognosis. PMID:23251265

  1. Imaging of Acute Pancreatitis.

    PubMed

    Thoeni, Ruedi F

    2015-11-01

    Acute pancreatitis is an acute inflammation of the pancreas. Several classification systems have been used in the past but were considered unsatisfactory. A revised Atlanta classification of acute pancreatitis was published that assessed the clinical course and severity of disease; divided acute pancreatitis into interstitial edematous pancreatitis and necrotizing pancreatitis; discerned an early phase (first week) from a late phase (after the first week); and focused on systemic inflammatory response syndrome and organ failure. This article focuses on the revised classification of acute pancreatitis, with emphasis on imaging features, particularly on newly-termed fluid collections and implications for the radiologist. PMID:26526433

  2. Intraluminal gastric pH in chronic pancreatitis.

    PubMed

    Bovo, P; Cataudella, G; Di Francesco, V; Vaona, B; Filippini, M; Marcori, M; Montesi, G; Rigo, L; Frulloni, L; Brunori, M P

    1995-02-01

    The aim of this study was to assess the circadian variations of intragastric pH in 28 inpatients with chronic pancreatitis (mean (SD) age 46.8 (12.4) years) and in 14 controls (45.4 (9.8)). pH Metry was performed using a monocrystalline antimony electrode placed in the body of the stomach under fluoroscopic control and connected up to a recorder (MKII Digitrapper, Synectics). The evaluation parameters, expressed as median and interquartile range, were: total period, postprandial periods (P1 and P2), interdigestive, and nocturnal phases. Patients with chronic pancreatitis were subdivided into three groups on the basis of severity of exocrine pancreatic insufficiency (secretin-caerulein test: lipase output at 60-90 min)--that is, those with severe insufficiency (chronic pancreatitis-SI: 13 patients, lipase output < 10% normal values and pancreolauryl test < 20%), those with only mild insufficiency (chronic pancreatitis-MI: seven patients), and those with normal secretion (chronic pancreatitis-NF: eight patients). The chronic pancreatitis-SI patients present significantly greater gastric acidification in the postprandial periods compared with controls (P1: p < 0.001; P2: p < 0.01), and with chronic pancreatitis-MI plus chronic pancreatitis-NF subjects (P1: p < 0.01; P2: p < 0.05), taken together. In conclusion, gastric acidity, exocrine pancreatic insufficiency, and impaired digestion are closely related during the course of chronic pancreatitis. PMID:7883232

  3. Pancreatic Pseudocyst Pleural Fistula in Gallstone Pancreatitis

    PubMed Central

    Abdalla, Sala; Nikolopoulos, Ioannis; Kerwat, Rajab

    2016-01-01

    Extra-abdominal complications of pancreatitis such as pancreaticopleural fistulae are rare. A pancreaticopleural fistula occurs when inflammation of the pancreas and pancreatic ductal disruption lead to leakage of secretions through a fistulous tract into the thorax. The underlying aetiology in the majority of cases is alcohol-induced chronic pancreatitis. The diagnosis is often delayed given that the majority of patients present with pulmonary symptoms and frequently have large, persistent pleural effusions. The diagnosis is confirmed through imaging and the detection of significantly elevated amylase levels in the pleural exudate. Treatment options include somatostatin analogues, thoracocentesis, endoscopic retrograde cholangiopancreatography (ERCP) with pancreatic duct stenting, and surgery. The authors present a case of pancreatic pseudocyst pleural fistula in a woman with gallstone pancreatitis presenting with recurrent pneumonias and bilateral pleural effusions. PMID:27274876

  4. EYA4 functions as tumor suppressor gene and prognostic marker in pancreatic ductal adenocarcinoma through β-catenin/ID2 pathway.

    PubMed

    Mo, Shi-Jing; Liu, Xin; Hao, Xiao-Yi; Chen, Wei; Zhang, Kun-Song; Cai, Jian-Peng; Lai, Jia-Ming; Liang, Li-Jian; Yin, Xiao-Yu

    2016-10-01

    Eye absent homolog 4 (EYA4) was initially found as key gene in controlling eye development in Drosophila. We recently found that EYA4 was an independent prognostic factor in hepatocellular carcinoma. Its biological functions in malignancies remained unknown. The present study aimed at investigating its biological functions, molecular mechanisms and prognostic values in pancreatic ductal adenocarcinoma (PDAC). Overexpression of EYA4 in PDAC cells inhibited proliferation and invasion in vitro and tumor growth in vivo. Depletion of EYA4 in PDAC cells enhanced proliferation and invasion in vitro and tumor growth in vivo. Mechanistically, armed with the serine/threonine-specific protein phosphatase activity, EYA4 dephosphorylated β-catenin at Ser675, blocked β-catenin nuclear translocation and inhibited ID2 transactivation. Consistently, EYA4 expression inversely correlated with the levels of p-Ser675-β-catenin and ID2 in tissues. EYA4 expression in PDAC tissues was significantly reduced as compared with adjacent non-tumoral tissues. EYA4 expression was an independent prognostic factor in PDAC, with a lower EYA4 level in association with shorter long-term survival and disease-free time. We showed that EYA4 functioned as tumor suppressor gene in PDAC via repressing β-catenin/ID2 activation, and was an independent prognostic factor in PDAC. PMID:27378242

  5. Smoke alarm tests may not adequately indicate smoke alarm function.

    PubMed

    Peek-Asa, Corinne; Yang, Jingzhen; Hamann, Cara; Young, Tracy

    2011-01-01

    Smoke alarms are one of the most promoted prevention strategies to reduce residential fire deaths, and they can reduce residential fire deaths by half. Smoke alarm function can be measured by two tests: the smoke alarm button test and the chemical smoke test. Using results from a randomized trial of smoke alarms, we compared smoke alarm response to the button test and the smoke test. The smoke alarms found in the study homes at baseline were tested, as well as study alarms placed into homes as part of the randomized trial. Study alarms were tested at 12 and 42 months postinstallation. The proportion of alarms that passed the button test but not the smoke test ranged from 0.5 to 5.8% of alarms; this result was found most frequently among ionization alarms with zinc or alkaline batteries. These alarms would indicate to the owner (through the button test) that the smoke alarm was working, but the alarm would not actually respond in the case of a fire (as demonstrated by failing the smoke test). The proportion of alarms that passed the smoke test but not the button test ranged from 1.0 to 3.0%. These alarms would appear nonfunctional to the owner (because the button test failed), even though the alarm would operate in response to a fire (as demonstrated by passing the smoke test). The general public is not aware of the potential for inaccuracy in smoke alarm tests, and burn professionals can advocate for enhanced testing methods. The optimal test to determine smoke alarm function is the chemical smoke test. PMID:21747329

  6. Platelet Function Tests: A Review of Progresses in Clinical Application

    PubMed Central

    Choi, Jae-Lim; Li, Shuhua

    2014-01-01

    The major goal of traditional platelet function tests has been to screen and diagnose patients who present with bleeding problems. However, as the central role of platelets implicated in the etiology of arterial thrombotic diseases such as myocardial infarction and stroke became widely known, platelet function tests are now being promoted to monitor the efficacy of antiplatelet drugs and also to potentially identify patients at increased risk of thrombosis. Beyond hemostasis and thrombosis, an increasing number of studies indicate that platelets play an integral role in intercellular communication, are mediators of inflammation, and have immunomodulatory activity. As new potential biomarkers and technologies arrive at the horizon, platelet functions testing appears to take on a new aspect. This review article discusses currently available clinical application of platelet function tests, placing emphasis on essential characteristics. PMID:24895576

  7. A Semi-Automated Functional Test Data Analysis Tool

    SciTech Connect

    Xu, Peng; Haves, Philip; Kim, Moosung

    2005-05-01

    The growing interest in commissioning is creating a demand that will increasingly be met by mechanical contractors and less experienced commissioning agents. They will need tools to help them perform commissioning effectively and efficiently. The widespread availability of standardized procedures, accessible in the field, will allow commissioning to be specified with greater certainty as to what will be delivered, enhancing the acceptance and credibility of commissioning. In response, a functional test data analysis tool is being developed to analyze the data collected during functional tests for air-handling units. The functional test data analysis tool is designed to analyze test data, assess performance of the unit under test and identify the likely causes of the failure. The tool has a convenient user interface to facilitate manual entry of measurements made during a test. A graphical display shows the measured performance versus the expected performance, highlighting significant differences that indicate the unit is not able to pass the test. The tool is described as semiautomated because the measured data need to be entered manually, instead of being passed from the building control system automatically. However, the data analysis and visualization are fully automated. The tool is designed to be used by commissioning providers conducting functional tests as part of either new building commissioning or retro-commissioning, as well as building owners and operators interested in conducting routine tests periodically to check the performance of their HVAC systems.

  8. Pancreatic blood flow in experimental acute pancreatitis

    SciTech Connect

    Berry, A.R.; Millar, A.M.; Taylor, T.V.

    1982-05-01

    The etiology and pathogenesis of acute necrotizing hemorrhagic pancreatitis remain controversial. Recent work has suggested that an early fall in pancreatic blood flow, causing ischemia, may be the initiating factor. Using an established rat model of hemorrhagic pancreatitis and the fractional indicator distribution technique with /sup 86/RbCl, pancreatic blood flow and tissue perfusion have been measured at various times in the condition. Six groups of ten rats were studied: control sham operation and pancreatitis groups were sacrificed at 1, 6, and 24 hr. Pancreatic blood flow (% of cardiac output) and perfusion (blood flow/g tissue) were measured. Blood flow was increased by a maximum of 53% at 1 hr (P less than 0.001) and remained elevated for 24 hr, and perfusion was increased by a maximum of 70% (P less than 0.001) at 1 hr and remained elevated at 6 hr. Pancreatic perfusion declines after 6 hr due to increasing gland edema. The results demonstrate a significant increase in pancreatic blood flow and perfusion in experimentally induced acute pancreatitis, suggesting a primary inflammatory response, and refute the ischemic etiological theory.

  9. Safety and Function Test Report for the SWIFT Wind Turbine

    SciTech Connect

    Mendoza, I.; Hur, J.

    2013-01-01

    This test was conducted as part of the U.S. Department of Energy's (DOE) Independent Testing project. This project was established to help reduce the barriers of wind energy expansion by providing independent testing results for small turbines. Three turbines where selected for testing at the National Wind Technology Center (NWTC) as a part of round two of the Small Wind Turbine Independent Testing project. Safety and Function testing is one of up to 5 tests that may be performed on the turbines. Other tests include power performance, duration, noise, and power quality. The results of the testing will provide the manufacturers with reports that may be used for small wind turbine certification.

  10. A Functional Test Platform for the Community Land Model

    SciTech Connect

    Xu, Yang; Thornton, Peter E; King, Anthony Wayne; Steed, Chad A; Gu, Lianhong; Schuchart, Joseph

    2014-01-01

    A functional test platform is presented to create direct linkages between site measurements and the process-based ecosystem model within the Community Earth System Models (CESM). The platform consists of three major parts: 1) interactive user interfaces, 2) functional test model and 3) observational datasets. It provides much needed integration interfaces for both field experimentalists and ecosystem modelers to improve the model s representation of ecosystem processes within the CESM framework without large software overhead.

  11. Pancreatitis-imaging approach

    PubMed Central

    Busireddy, Kiran K; AlObaidy, Mamdoh; Ramalho, Miguel; Kalubowila, Janaka; Baodong, Liu; Santagostino, Ilaria; Semelka, Richard C

    2014-01-01

    Pancreatitis is defined as the inflammation of the pancreas and considered the most common pancreatic disease in children and adults. Imaging plays a significant role in the diagnosis, severity assessment, recognition of complications and guiding therapeutic interventions. In the setting of pancreatitis, wider availability and good image quality make multi-detector contrast-enhanced computed tomography (MD-CECT) the most used imaging technique. However, magnetic resonance imaging (MRI) offers diagnostic capabilities similar to those of CT, with additional intrinsic advantages including lack of ionizing radiation and exquisite soft tissue characterization. This article reviews the proposed definitions of revised Atlanta classification for acute pancreatitis, illustrates a wide range of morphologic pancreatic parenchymal and associated peripancreatic changes for different types of acute pancreatitis. It also describes the spectrum of early and late chronic pancreatitis imaging findings and illustrates some of the less common types of chronic pancreatitis, with special emphasis on the role of CT and MRI. PMID:25133027

  12. Acute recurrent pancreatitis: Etiopathogenesis, diagnosis and treatment

    PubMed Central

    Testoni, Pier Alberto

    2014-01-01

    Acute recurrent pancreatitis (ARP) refers to a clinical entity characterized by episodes of acute pancreatitis which occurs on more than one occasion. Recurrence of pancreatitis generally occurs in a setting of normal morpho-functional gland, however, an established chronic disease may be found either on the occasion of the first episode of pancreatitis or during the follow-up. The aetiology of ARP can be identified in the majority of patients. Most common causes include common bile duct stones or sludge and bile crystals; sphincter of oddi dysfunction; anatomical ductal variants interfering with pancreatic juice outflow; obstruction of the main pancreatic duct or pancreatico-biliary junction; genetic mutations; alcohol consumption. However, despite diagnostic technologies, the aetiology of ARP still remains unknown in up to 30% of cases: in these cases the term “idiopathic” is used. Because occult bile stone disease and sphincter of oddi dysfunction account for the majority of cases, cholecystectomy, and eventually the endoscopic biliary and/or pancreatic sphincterotomy are curative in most of cases. Endoscopic biliary sphincterotomy appeared to be a curative procedure per se in about 80% of patients. Ursodeoxycholic acid oral treatment alone has also been reported effective for treatment of biliary sludge. In uncertain cases toxin botulin injection may help in identifying some sphincter of oddi dysfunction, but this treatment is not widely used. In the last twenty years, pancreatic endotherapy has been proven effective in cases of recurrent pancreatitis depending on pancreatic ductal obstruction, independently from the cause of obstruction, and has been widely used instead of more aggressive approaches. PMID:25493002

  13. IDENTIFICATION AND CHARACTERIZATION OF DISEASE USING PULMONARY FUNCTION TESTS

    EPA Science Inventory

    Abstract
    Pulmonary function testing is used routinely in human medicine to objectively define functional deficits in individuals with respiratory disease. Despite the fact that respiratory disease is a common problem in veterinary medicine, evaluation of the small animal pa...

  14. Cryosurgery for pancreatic cancer

    PubMed Central

    Xu, Kecheng; Yang, Daming

    2013-01-01

    The procedure of pancreatic cryosurgery is performed with intraoperative or percutaneous approaches. Based on current data and our initial experience, cryoablation appears to be a feasible, potentially safe and promising option in patients with locally advanced and unresectable pancreatic cancer. It is suggested that there are almost no known contraindications to the use of cryosurgery for pancreatic cancer. For most patients with pancreatic cancer, cryosurgery can substitute conventional surgery. PMID:25083453

  15. To Be(ta Cell) or Not to Be(ta cell): New Mouse Models for Studying Gene Function in the Pancreatic β-Cell.

    PubMed

    Estall, Jennifer L; Screaton, Robert A

    2015-07-01

    A challenge in the pancreatic β-cell field has been to identify a promoter fragment that is active only in the β-cell compartment and inactive in other regions, such as the hypothalamic region of the brain. The presence of Cre recombinase alone in some models may also affect glucoregulation, confounding interpretation of gene function in the β-cell. A paper presented within describes the development and characterization of 2 new transgenic mice expressing Cre recombinase under the mouse insulin1 promoter that are useful for β-cell-specific gene ablation: the first is constitutive and coexpresses DsRed (Ins1-Cre-DsRed); the second allows β-cell-specific expression of the reverse tetracycline-controlled transactivator, which can be used for drug-dependent expression of a target gene of interest for overexpression studies. These novel models show robust specificity and efficiency and will be valuable tools for functional studies of gene action in β-cells, potentially alleviating current issues associated with previously available mouse lines. PMID:26091426

  16. Specific 13C functional pathways as diagnostic targets in gastroenterology breath-tests: tricks for a correct interpretation.

    PubMed

    Pizzoferrato, M; Del Zompo, F; Mangiola, F; Lopetuso, L R; Petito, V; Cammarota, G; Gasbarrini, A; Scaldaferri, F

    2013-01-01

    Breath tests are non-invasive, non-radioactive, safe, simple and effective tests able to determine significant metabolic alterations due to specific diseases or lack of specific enzymes. Carbon isotope (13)C, the stable-non radioactive isotope of carbon, is the most used substrate in breath testing, in which (13)C/(12)C ratio is measured and expressed as a delta value, a differences between readings and a fixed standard. (13)C/(12)C ratio is measured with isotope ratio mass spectrometry or non-dispersive isotope-selective infrared spectrometer and generally there is a good agreement between these techniques in the isotope ratio estimation. (13)C/(12)C ratio can be expressed as static measurement (like delta over baseline in urea breath test) or as dynamic measurement as percent dose recovery, but more dosages are necessary. (13)C Breath-tests are involved in many fields of interest within gastroenterology, such as detection of Helicobacter pylori infection, study of gastric emptying, assessment of liver and exocrine pancreatic functions, determination of oro-caecal transit time, evaluation of absorption and to a lesser extend detection of bacterial overgrowth. The use of every single test in a clinical setting is vary depending on accuracy and substrate costs. This review is meant to present (13)C the meaning of (13)C/(12)C ratio and static and dynamic measure and, finally, the instruments dedicated to its use in gastroenterology. A brief presentation of (13)C breath tests in gastroenterology is also provided. PMID:24443068

  17. Protein alterations associated with pancreatic cancer and chronic pancreatitis found in human plasma using global quantitative proteomics profiling

    PubMed Central

    Pan, Sheng; Chen, Ru; Crispin, David A.; May, Damon; Stevens, Tyler; McIntosh, Martin; Bronner, Mary P.; Ziogas, Argyrios; Anton-Culver, Hoda; Brentnall, Teresa A.

    2011-01-01

    Pancreatic cancer is a lethal disease that is difficult to diagnose at early stages when curable treatments are effective. Biomarkers that can improve current pancreatic cancer detection would have great value in improving patient management and survival rate. A large scale quantitative proteomics study was performed to search for the plasma protein alterations associated with pancreatic cancer. The enormous complexity of the plasma proteome and the vast dynamic range of protein concentration therein present major challenges for quantitative global profiling of plasma. To address these challenges, multi-dimensional fractionation at both protein and peptide levels was applied to enhance the depth of proteomics analysis. Employing stringent criteria, more than thirteen hundred proteins total were identified in plasma across 8-orders of magnitude in protein concentration. Differential proteins associated with pancreatic cancer were identified, and their relationship with the proteome of pancreatic tissue and pancreatic juice from our previous studies was discussed. A subgroup of differentially expressed proteins was selected for biomarker testing using an independent cohort of plasma and serum samples from well-diagnosed patients with pancreatic cancer, chronic pancreatitis and non-pancreatic disease controls. Using ELISA methodology, the performance of each of these protein candidates was benchmarked against CA19-9, the current gold standard for a pancreatic cancer blood test. A composite marker of TIMP1 and ICAM1 demonstrate significantly better performance than CA19-9 in distinguishing pancreatic cancer from the non-pancreatic disease controls and chronic pancreatitis controls. In addition, protein AZGP1 was identified as a biomarker candidate for chronic pancreatitis. The discovery and technical challenges associated with plasma-based quantitative proteomics are discussed and may benefit the development of plasma proteomics technology in general. The protein

  18. BPC 157 therapy to detriment sphincters failure-esophagitis-pancreatitis in rat and acute pancreatitis patients low sphincters pressure.

    PubMed

    Petrovic, I; Dobric, I; Drmic, D; Sever, M; Klicek, R; Radic, B; Brcic, L; Kolenc, D; Zlatar, M; Kunjko, K; Jurcic, D; Martinac, M; Rasic, Z; Boban Blagaic, A; Romic, Z; Seiwerth, S; Sikiric, P

    2011-10-01

    Possibly, acute esophagitis and pancreatitis cause each other, and we focused on sphincteric failure as the common causative key able to induce either esophagitis and acute pancreatitis or both of them, and thereby investigate the presence of a common therapy nominator. This may be an anti-ulcer pentadecapeptide BPC 157 (tested for inflammatory bowel disease, wound treatment) affecting esophagitis, lower esophageal and pyloric sphincters failure and acute pancreatitis (10 μg/kg, 10 ng/kg intraperitoneally or in drinking water). The esophagitis-sphincter failure procedure (i.e., insertion of the tubes into the sphincters, lower esophageal and pyloric) and acute pancreatitis procedure (i.e., bile duct ligation) were combined in rats. Esophageal manometry was done in acute pancreatitis patients. In rats acute pancreatitis procedure produced also esophagitis and both sphincter failure, decreased pressure 24 h post-surgery. Furthermore, bile duct ligation alone immediately declines the pressure in both sphincters. Vice versa, the esophagitis-sphincter failure procedure alone produced acute pancreatitis. What's more, these lesions (esophagitis, sphincter failure, acute pancreatitis when combined) aggravate each other (tubes into sphincters and ligated bile duct). Counteraction occurred by BPC 157 therapies. In acute pancreatitis patients lower pressure at rest was in both esophageal sphincters in acute pancreatitis patients. We conclude that BPC 157 could cure esophagitis/sphincter/acute pancreatitis healing failure. PMID:22204800

  19. Artificial islets from hybrid spheroids of three pancreatic cell lines.

    PubMed

    Jo, Y H; Jang, I J; Nemeno, J G; Lee, S; Kim, B Y; Nam, B M; Yang, W; Lee, K M; Kim, H; Takebe, T; Kim, Y S; Lee, J I

    2014-05-01

    Pancreatic islets have been the focus of recent studies exploring the pathologic mechanisms of diabetes mellitus as well as more effective and radical treatments for this disease. Islet transplantation is a promising therapeutic strategy; however, isolation of pancreatic islets for this purpose has been challenging, because the technique is time consuming and technically difficult, and tissue handling can be variable. Pseudo-islets can be used as an alternative to naïve islets, but require cellular sources or artificial materials. In this study, pancreas-derived cells were used to generate pseudo-islets. Because the pancreas is composed of a variety of cell types, namely α cells, β cells, δ cells, and other pancreatic cells that perform different functions, we used 3 different cell lines-NIT-1 (a β-cell line), α TC1 clone 6 (an α-cell line), and TGP52 (a pancreatic epithelial-like cell line)-which we cocultured in nonadhesive culture plates to produce hybrid cellular spheroids. These pseudo-islets had an oval shape and were morphologically similar to naïve islets; additionally, they expressed and secreted the pancreatic hormones insulin, glucagon, and somatostatin, as confirmed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. The results demonstrate that pseudo-islets that mimic naïve islets can be successfully generated by a coculture method. These artificial islets can potentially be used for in vitro tests related to diabetes mellitus, specifically, in drug discovery or for investigating pathology. Moreover, they can be useful for examining basic questions pertaining to cell-cell interactions and tissue development. PMID:24815150

  20. SP-100 nuclear assembly test - Test assembly functional requirements and system arrangement

    NASA Astrophysics Data System (ADS)

    Fallas, T. T.; Gluck, Robert; Motwani, Kumar; Clay, Harold; O'Neill, Gerald

    This paper describes the functional requirements and the system that will be tested to validate the reactor, flight shield, and flight controller of the SP-100 Generic Flight System. The Nuclear Assembly Test consists of the test article (SP-100 reactor with control devices and the flight shield) and its supporting systems.

  1. Pancreatic cancer risk in hereditary pancreatitis

    PubMed Central

    Weiss, Frank U.

    2014-01-01

    Inflammation is part of the body's immune response in order to remove harmful stimuli—like pathogens, irritants or damaged cells—and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1) gene have been identified as risk factors of the disease. Hereditary pancreatitis (HP) is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. HP often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of HP patients to develop pancreatic cancer. PMID:24600409

  2. An automated miniaturized Haploscope for testing binocular visual function

    NASA Technical Reports Server (NTRS)

    Decker, T. A.; Williams, R. E.; Kuether, C. L.; Wyman-Cornsweet, D.

    1976-01-01

    A computer-controlled binocular vision testing device has been developed as one part of a system designed for NASA to test the vision of astronauts during spaceflight. The device, called the Mark III Haploscope, utilizes semi-automated psychophysical test procedures to measure visual acuity, stereopsis, phorias, fixation disparity and accommodation/convergence relationships. All tests are self-administered, yield quantitative data and may be used repeatedly without subject memorization. Future applications of this programmable, compact device include its use as a clinical instrument to perform routine eye examinations or vision screening, and as a research tool to examine the effects of environment or work-cycle upon visual function.

  3. Testing for cognitive function in animals in a regulatory context.

    PubMed

    Bushnell, Philip J

    2015-01-01

    Superior cognitive functions have allowed the human species to proliferate in a world of incredible biological diversity. Threats to these essential capacities cannot be ignored, and a strategy is needed to evaluate the hazard posed by exposure to chemical and other agents. Because people exposed to chemicals often complain about confusion and forgetfulness, it is commonly thought that cognitive functions should be sensitive indicators of adverse consequences of chemical exposure. For these reasons, complex tests of cognitive function have been developed and deployed in experimental animal laboratories for decades. However, the results of these tests are rarely used as points of departure for chemical risk assessments. Due to their high cost in time, animals, and equipment, the efficacy and utility of these tests need to be evaluated in relation to cheaper and faster whole-animal screening methods. This review examines evidence for the assertions that cognitive functions represent uniquely sensitive indicators of chemical exposure, and that animal models of these functions are necessary to detect and quantify the neurotoxicity of chemicals. Studies conducted since the early 1980s to compare these approaches to assess the neurotoxicity of chemicals are reviewed for both adult and perinatal exposures in experimental rodents. Forty-one studies of 35 chemicals were found that directly compared acute effects using complex tests (i.e., tests that require training animals) with acute effects using screening tests (i.e., tests that do not require training animals) in adult rodents. Complex tests detected effects of three substances (bitertanol, iso-amyl nitrite, and Pfiesteria toxin) that had no effect on screening tests; for an additional five chemicals (carbaryl, deltamethrin, methyl mercury, tetraethyl tin, and Isopar-C), complex tests identified effects at lower doses than did screening tests. Fewer comparable cases were found for developmental exposures: screening and

  4. Pancreatic islet function in omega3 fatty acid-depleted rats: Glucose metabolism and nutrient-stimulated insulin release.

    PubMed

    Oguzhan, Berrin; Zhang, Ying; Louchami, Karim; Courtois, Philippe; Portois, Laurence; Chardigny, Jean-Michel; Malaisse, Willy J; Carpentier, Yvon A; Sener, Abdullah

    2006-06-01

    In order to gain information on the determinism of the perturbation of fuel homeostasis in situations characterized by a depletion in long-chain polyunsaturated omega3 fatty acids (omega3), the metabolic and hormonal status of omega3-depleted rats (second generation) was examined. When required, these rats were injected intravenously 120 min before sacrifice with a novel medium-chain triglyceride-fish oil emulsion able to provoke a rapid and sustained increase of the omega3 content in cell phospholipids. The measurement of plasma glucose, insulin, phospholipid, triglyceride, and unesterified fatty acid concentration indicated modest insulin resistance in the omega3-depleted rats. The plasma triglyceride and phospholipid concentrations were decreased in the omega3-depleted rats with abnormally low contribution of omega3 in both circulating and pancreatic islet lipids. The protein, insulin, and lipid content of the islets, as well as their intracellular and extracellular spaces, were little affected in the omega3-depleted rats. The metabolism of D-glucose in the islets of omega3-depleted rats was characterized by a lesser increase in D-[5-3H]glucose utilization and D-[U-14C]glucose oxidation in response to a given rise in hexose concentration and an abnormally low ratio between D-glucose oxidation and utilization. These abnormalities could be linked to an increased metabolism of endogenous fatty acids with resulting alteration of glucokinase kinetics. The release of insulin evoked by D-glucose, at a close-to-physiological concentration (8.3 mM), was increased in the omega3-depleted rats, this being considered as consistent with their insulin resistance. Relative to such a release, that evoked by a further rise in D-glucose concentration or by non-glucidic nutrients was abnormally high in omega3-depleted rats, and restored to a normal level after of the intravenous injection of the omega3-rich medium-chain triglyceride-fish oil emulsion. Because the latter procedure

  5. Biology of pancreatic cancer.

    PubMed Central

    Poston, G J; Gillespie, J; Guillou, P J

    1991-01-01

    Pancreatic cancer is the fifth leading cause of death from malignant disease in Western society. Apart from the fortunate few patients who present with a resectable small pancreatic adenocarcinoma, conventional treatment offers no hope of cure and has little palliative value. Over the past two decades major steps have been made in our understanding of the biology of pancreatic growth and neoplasia. This review sets out to explore these advances, firstly in the regulation of normal pancreatic growth, and secondly the mechanism which may be involved in malignant change of the exocrine pancreas. From an understanding of this new biology, new treatment strategies may be possible for patients with pancreatic cancer. PMID:1855689

  6. [Features of therapy for chronic pancreatitis associated with anxious depressive disorders in railway workers].

    PubMed

    Ushakov, I B; Lubavskaya, S S; Batishcheva, G A; Chernov, Yu N

    2016-01-01

    The article presents data on peculiarities of chronic pancreatitis course in railway transport workers (engine operators, engine operator assistants, dispatchers) with anxious depressive disorders. Pain and dyspepsia in patients with affective disorders appeared to be constant and more intense than in the patients without concomitant anxious depression. Psychophysiologic tests in 83% of patients with comorbid conditions revealed significant psychomotor dullness manifested in reliable lower speed of visual motor reactions. Pharmacologic correction via anxiolytics (Adaptol, Afobasol) combined with standard therapy for chronic pancreatitis exacerbation enabled to improve clinical symptoms, but Adaptol appeared to slow simple visual motor reactions, therefore has to be ruled out in engine operators. Pharmacotherapy of chronic pancreatitis, that included Afobasol in addition to standard treatment, promoted reliable improvement of occupationally important psychophysiologic functions. This study received a patent. PMID:27396150

  7. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children

    PubMed Central

    Chong, Sze Yee; Coleman, Lee; MacGregor, Duncan; Hardikar, Winita; Oliver, Mark R.

    2016-01-01

    We report 3 children who presented with fever and abdominal pain, deranged liver function tests, and on abdominal ultrasound were found to have an enlarged pancreas, substantial abdominal lymphadenopathy, and extrahepatic biliary duct dilatation. After ruling out malignancy, probable immunoglobulin G4-related disease (IgG4RD) associated with autoimmune pancreatitis was considered. This condition was first described in the adults and often mimics pancreatic cancer. It can involve multiple organs, either synchronously or metachronously, and is rarely reported in children. The disorder mostly responds to corticosteroid therapy and other immune suppression. We highlight the difficulty in diagnosing autoimmune pancreatitis/IgG4-related disease in children and illustrate the difference between pediatric and adult presentation. PMID:27622194

  8. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children.

    PubMed

    Bolia, Rishi; Chong, Sze Yee; Coleman, Lee; MacGregor, Duncan; Hardikar, Winita; Oliver, Mark R

    2016-07-01

    We report 3 children who presented with fever and abdominal pain, deranged liver function tests, and on abdominal ultrasound were found to have an enlarged pancreas, substantial abdominal lymphadenopathy, and extrahepatic biliary duct dilatation. After ruling out malignancy, probable immunoglobulin G4-related disease (IgG4RD) associated with autoimmune pancreatitis was considered. This condition was first described in the adults and often mimics pancreatic cancer. It can involve multiple organs, either synchronously or metachronously, and is rarely reported in children. The disorder mostly responds to corticosteroid therapy and other immune suppression. We highlight the difficulty in diagnosing autoimmune pancreatitis/IgG4-related disease in children and illustrate the difference between pediatric and adult presentation. PMID:27622194

  9. Combination of the dipeptidyl peptidase IV inhibitor LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] with the angiotensin II type 1 receptor antagonist valsartan [N-(1-oxopentyl)-N-[[2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]methyl]-L-valine] enhances pancreatic islet morphology and function in a mouse model of type 2 diabetes.

    PubMed

    Cheng, Qianni; Law, Pui Ki; de Gasparo, Marc; Leung, Po Sing

    2008-12-01

    LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] is an inhibitor of dipeptidyl peptidase IV that delays the degradation of glucagon-like peptide-1 (GLP-1). Valsartan [N-(1-oxopentyl)-N-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-l-valine] is an antagonist of the angiotensin II type 1 receptor (AT1R) that reduces the incidence of type 2 diabetes mellitus. LAF237 and valsartan act on a common target through separate pathways to improve pancreatic islet cell function. We hypothesize that the combination of these two drugs acts in a synergistic or additive manner on islet function and structure. To test this hypothesis, we performed in vitro and in vivo studies. To measure the acute effect of the treatment, pancreatic islets of db/db mice were isolated and stimulated in vitro with glucose in the presence of valsartan (1 microM) and exendin-4 (100 nM), a GLP-1 receptor agonist. Combination treatment with valsartan and exendin-4 significantly enhanced glucose-stimulated insulin secretion from isolated islets. For studies of chronic effect, db/db mice received LAF237 (1 mg/kg/day) and/or valsartan (10 mg/kg/day). Islet cell reactive oxygen species (ROS), proliferation, apoptosis, fibrosis, beta-cell area, and glucose homeostasis were evaluated after 8 weeks of treatment, which showed that combination treatment resulted in a significant increase in pancreatic islet beta-cell area compared with monotherapy. This beneficial effect correlated with an increase in beta-cell proliferation and a decrease in ROS-induced islet apoptosis and fibrosis. These in vitro and in vivo data indicate that combination treatment with LAF237 and valsartan has significant beneficial additive effects on pancreatic beta-cell structure and function compared with their respective monotherapeutic effects. PMID:18787107

  10. Psychometric tests for assessment of brain function after solvent exposure.

    PubMed

    Rasmussen, K; Jeppesen, H J; Sabroe, S

    1993-11-01

    Psychometric testing is a key issue in neuropsychological toxicology assessment. Evaluation of methods for assessing general intellectual impairment is necessary as conventional neurology has been shown to be insensitive to the neurotoxic effects of solvents and metals. This study presents an analysis of a psychometric test battery from an investigation of psycho-organic syndrome in a historical cohort of 96 metal degreasers with long-term exposure to solvents, particularly trichloroethylene. The neuropsychological test battery was a combination of Wechsler Adult Intelligence Scale (WAIS), Luria, and tests developed in Scandinavia. Linear regression analysis showed a significant dose-response relation between increasing cumulative solvent exposure and impaired psychometric test performance in 9 out of 15 tests. Multivariate analysis, however, suggests that much of the variance was due to confounding variables, especially age, and to a lesser degree, primary intellectual function and word blindness. After control for confounding factors the strongest association with solvent exposure occurred for the following three tests: acoustic-motor function, Paced Auditory Serial Addition Test (PASAT), and the visual gestalt test. PMID:8266931

  11. Pancreatic islet transplantation

    PubMed Central

    Corrêa-Giannella, Maria Lúcia; Raposo do Amaral, Alexandre S

    2009-01-01

    Background No formulation of exogenous insulin available to date has yet been able to mimic the physiological nictemeral rhythms of this hormone, and despite all engineering advancements, the theoretical proposal of developing a mechanical replacement for pancreatic β cell still has not been reached. Thus, the replacement of β cells through pancreas and pancreatic islet transplantation are the only concrete alternatives for re-establishing the endogenous insulin secretion in type 1 diabetic patients. Since only 1 to 1.5% of the pancreatic mass corresponds to endocrine tissue, pancreatic islets transplantation arises as a natural alternative. Data from the International Islet Transplant Registry (ITR) from 1983 to December 2000 document a total of 493 transplants performed around the world, with progressively worse rates of post-transplant insulin independence. In 2000, the "Edmonton Protocol" introduced several modifications to the transplantation procedure, such as the use of a steroid-free immunosuppression regimen and transplantation of a mean islet mass of 11,000 islet equivalents per kilogram, which significantly improved 1-year outcomes. Although the results of a 5-year follow-up in 65 patients demonstrated improvement in glycemic instability in a significant portion of them, only 7.5% of the patients have reached insulin independence, indicating the need of further advances in the preservation of the function of transplanted islet. In addition to the scarcity of organs available for transplantation, islets transplantation still faces major challenges, specially those related to cell loss during the process of islet isolation and the losses related to the graft site, apoptosis, allorejection, autoimmunity, and immunosuppression. The main strategies to optimize islet transplantation aim at improving all these aspects. Conclusion Human islet transplantation should be regarded as an intervention that can decrease the frequency of severe hypoglycemic episodes

  12. The structural and functional recovery of pancreatic β-cells in type 1 diabetes mellitus induced mesenchymal stem cell-conditioned medium

    PubMed Central

    Nugroho, Widagdo Sri; Kusindarta, Dwi Liliek; Susetya, Heru; Fitriana, Ida; Mulyani, Guntari Titik; Fibrianto, Yuda Heru; Haryanto, Aris; Budipitojo, Teguh

    2016-01-01

    Aim: Various studies have shown that secreted factors alone in culture medium without stem cell are capable of repairing tissues by itself in various conditions involving damaged tissue/organ. Therefore, this study was aimed to investigate the role of human umbilical cord mesenchymal stem cell-derived conditioned medium (CM) on the recovery of pancreatic β-cells in Wistar rats (Rattus norvegicus) with type 1 diabetes mellitus. Materials and Methods: The 0.05 ml CM induction was applied to the diabetic group of rats in weeks 1, 2, 3, and 4. 1 week after each CM induction, insulin concentration was analyzed using ELISA. The pancreas was divided into 3 regions, processed by paraffin method, stained with hematoxylin-eosin, and immunohistochemical method for insulin. Results: This study indicated the decrease in the total number of islets and insulin concentration after the injection of single dose of alloxan. The exocrine acini were also damaged. Microscopic observation detected the presence of small islets in the diabetic group 1 week after the first 0.05 ml CM induction. The number and size of the islets increased in line with the CM doses and time of inductions. Immunohistochemically, the presence of low intensity of insulin-positive cells could be recognized at the splenic and duodenal regions of the pancreas, but not gastric region, 1 week after the first and second 0.05 ml CM induction. The intensity of staining and the number of insulin-positive cells increased dramatically in 1 week after the third and fourth 0.05 ml of CM induction in all regions of the pancreas. The data of insulin blood concentration showed clear differences between the second and the fourth induction of 0.05 ml CM induction. Conclusions: This study showed very strong evidence on the role of human umbilical cord mesenchymal stem cell-derived CM in recovering the pancreatic β-cells damage in Wistar rats (R. norvegicus) with type 1 diabetes mellitus, structurally and functionally. PMID

  13. Pancreatic Cancer Genetics

    PubMed Central

    Amundadottir, Laufey T.

    2016-01-01

    Although relatively rare, pancreatic tumors are highly lethal [1]. In the United States, an estimated 48,960 individuals will be diagnosed with pancreatic cancer and 40,560 will die from this disease in 2015 [1]. Globally, 337,872 new pancreatic cancer cases and 330,391 deaths were estimated in 2012 [2]. In contrast to most other cancers, mortality rates for pancreatic cancer are not improving; in the US, it is predicted to become the second leading cause of cancer related deaths by 2030 [3, 4]. The vast majority of tumors arise in the exocrine pancreas, with pancreatic ductal adenocarcinoma (PDAC) accounting for approximately 95% of tumors. Tumors arising in the endocrine pancreas (pancreatic neuroendocrine tumors) represent less than 5% of all pancreatic tumors [5]. Smoking, type 2 diabetes mellitus (T2D), obesity and pancreatitis are the most consistent epidemiological risk factors for pancreatic cancer [5]. Family history is also a risk factor for developing pancreatic cancer with odds ratios (OR) ranging from 1.7-2.3 for first-degree relatives in most studies, indicating that shared genetic factors may play a role in the etiology of this disease [6-9]. This review summarizes the current knowledge of germline pancreatic cancer risk variants with a special emphasis on common susceptibility alleles identified through Genome Wide Association Studies (GWAS). PMID:26929738

  14. Diabetes and Pancreatic Cancer

    PubMed Central

    Li, Donghui

    2011-01-01

    Type 2 diabetes mellitus is likely the third modifiable risk factor for pancreatic cancer after cigarette smoking and obesity. Epidemiological investigations have found that long-term type 2 diabetes mellitus is associated with a 1.5- to 2.0-fold increase in the risk of pancreatic cancer. A causal relationship between diabetes and pancreatic cancer is also supported by findings from prediagnostic evaluations of glucose and insulin levels in prospective studies. Insulin resistance and associated hyperglycemia, hyperinsulinemia, and inflammation have been suggested to be the underlying mechanisms contributing to development of diabetes-associated pancreatic cancer. Signaling pathways that regulate the metabolic process also play important roles in cell proliferation and tumor growth. Use of the antidiabetic drug metformin has been associated with reduced risk of pancreatic cancer in diabetics and recognized as an antitumor agent with the potential to prevent and treat this cancer. On the other hand, new-onset diabetes may indicate subclinical pancreatic cancer, and patients with new-onset diabetes may constitute a population in whom pancreatic cancer can be detected early. Biomarkers that help define high-risk individuals for clinical screening for pancreatic cancer are urgently needed. Why pancreatic cancer causes diabetes and how diabetes affects the clinical outcome of pancreatic cancer have yet to be fully determined. Improved understanding of the pathological mechanisms shared by diabetes and pancreatic cancer would be the key to the development of novel preventive and therapeutic strategies for this cancer. PMID:22162232

  15. Executive function on the Psychology Experiment Building Language tests.

    PubMed

    Piper, Brian J; Li, Victoria; Eiwaz, Massarra A; Kobel, Yuliyana V; Benice, Ted S; Chu, Alex M; Olsen, Reid H J; Rice, Douglas Z; Gray, Hilary M; Mueller, Shane T; Raber, Jacob

    2012-03-01

    The measurement of executive function has a long history in clinical and experimental neuropsychology. The goal of the present report was to determine the profile of behavior across the lifespan on four computerized measures of executive function contained in the recently developed Psychology Experiment Building Language (PEBL) test battery http://pebl.sourceforge.net/ and evaluate whether this pattern is comparable to data previously obtained with the non-PEBL versions of these tests. Participants (N = 1,223; ages, 5-89 years) completed the PEBL Trail Making Test (pTMT), the Wisconsin Card Sort Test (pWCST; Berg, Journal of General Psychology, 39, 15-22, 1948; Grant & Berg, Journal of Experimental Psychology, 38, 404-411, 1948), the Tower of London (pToL), or a time estimation task (Time-Wall). Age-related effects were found over all four tests, especially as age increased from young childhood through adulthood. For several tests and measures (including pToL and pTMT), age-related slowing was found as age increased in adulthood. Together, these findings indicate that the PEBL tests provide valid and versatile new research tools for measuring executive functions. PMID:21534005

  16. Functional Performance Testing After Anterior Cruciate Ligament Reconstruction

    PubMed Central

    Abrams, Geoffrey D.; Harris, Joshua D.; Gupta, Anil K.; McCormick, Frank M.; Bush-Joseph, Charles A.; Verma, Nikhil N.; Cole, Brian J.; Bach, Bernard R.

    2014-01-01

    Background: When to allow an athlete to return to unrestricted sporting activity after anterior cruciate ligament (ACL) reconstruction remains controversial. Purpose: To report the results of functional performance testing reported in the literature for individuals at differing time points following ACL reconstruction and to examine differences between graft types. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of Medline, Scopus, and Cochrane Central Register of Controlled Trials was performed using PRISMA guidelines. Inclusion criteria were English-language studies that examined any functional rehabilitation test from 6 months to 2 years following ACL reconstruction. All patient-, limb-, and knee-specific demographics were extracted from included investigations. All functional rehabilitation tests were analyzed and compared when applicable. Results: The search term returned a total of 890 potential studies, with 88 meeting inclusion and exclusion criteria. A total of 4927 patients were included, of which 66% were male. The mean patient age was 26.5 ± 3.4 years. The predominant graft choices for reconstruction were bone–patellar tendon–bone (BPTB) autograft (59.8%) and hamstring autograft (37.9%). The most commonly reported functional tests were the hop tests. The results of these functional tests, as reported in the Limb Symmetry Index (LSI), improved with increasing time, with nearly all results greater than 90% at 1 year following primary ACL reconstruction. At 6 months postoperatively, a number of isokinetic strength measurements failed to reach 80% LSI, most commonly isokinetic knee extension testing in both BPTB and hamstring autograft groups. The knee flexion strength deficit was significantly less in the BPTB autograft group as compared with those having hamstring autograft at 1 year postoperatively, while no significant differences were found in isokinetic extension strength between the 2 groups. Conclusion: Hop

  17. Sex differences between APPswePS1dE9 mice in A-beta accumulation and pancreatic islet function during the development of Alzheimer's disease.

    PubMed

    Li, Xin; Feng, Ying; Wu, Wei; Zhao, Jia; Fu, Chunmei; Li, Yang; Ding, Yangnan; Wu, Binghuo; Gong, Yanju; Yang, Guizhi; Zhou, Xue

    2016-08-01

    The pathogenesis of Alzheimer's disease (AD), a type of neurodegenerative disease characterized by learning and memory impairment, is often associated with pathological features, such as amyloid-beta (Aβ) accumulation and insulin resistance. The transgenic mouse, APPswePS1dE9 (APP/PS1), is one of the most commonly used animal models in pathogenesis studies of AD. The purpose of this study is to investigate the sex differences between APP/PS1 mice in the pathogenesis of AD. The impairment of glucose and insulin tolerance was found to develop earlier in male APP/PS1 mice than in females. Plasma insulin levels were significantly decreased in male APP/PS1 mice, while total cholesterol levels in male APP/PS1 mice were higher than those in females. Triglyceride levels in male mice in both the wild-type (WT) and APP/PS1 groups were higher than in their female littermates. Soluble and insoluble Aβ levels in female APP/PS1 mouse brains were higher than those in males. And the learning and memorizing abilities of female APP/PS1 mice were poorer than those of males. Our results concluded that there were sex differences in Aβ formation, pancreatic islet function and insulin sensitivity between male and female APP/PS1 mice during the pathogenesis of AD. PMID:26519428

  18. Multimodal function of the sweet taste receptor expressed in pancreatic β-cells: generation of diverse patterns of intracellular signals by sweet agonists.

    PubMed

    Nakagawa, Yuko; Nagasawa, Masahiro; Mogami, Hideo; Lohse, Martin; Ninomiya, Yuzo; Kojima, Itaru

    2013-01-01

    The sweet taste receptor is expressed in the taste bud and is activated by numerous sweet molecules with diverse chemical structures. It is, however, not known whether these sweet agonists induce a similar cellular response in target cells. Using MIN6 cells, a pancreatic β-cell line expressing endogenous sweet taste receptor, we addressed this question by monitoring changes in cytoplasmic Ca2+ ([Ca2+]i) and cAMP ([cAMP]i) induced by four sweet taste receptor agonists. Glycyrrhizin evoked sustained elevation of [Ca2+]i but [cAMP]i was not affected. Conversely, an artificial sweetener saccharin induced sustained elevation of [cAMP]i but did not increase [Ca2+]i. In contrast, sucralose and acesulfame K induced rapid and sustained increases in both [Ca2+]i and [cAMP]i. Although the latter two sweeteners increased [Ca2+]i and [cAMP]i, their actions were not identical: [Ca2+]i response to sucralose but not acesulfame K was inhibited by gurmarin, an antagonist of the sweet taste receptor which blocks the gustducin-dependent pathway. In addition, [Ca2+]i response to acesulfame K but not to sucralose was resistant to a Gq inhibitor. These results indicate that four types of sweeteners activate the sweet taste receptor differently and generate distinct patterns of intracellular signals. The sweet taste receptor has amazing multimodal functions producing multiple patterns of intracellular signals. PMID:23933592

  19. Intermittent Hypoxia Exacerbates Pancreatic β-Cell Dysfunction in A Mouse Model of Diabetes Mellitus

    PubMed Central

    Sherwani, Shariq I.; Aldana, Carolyn; Usmani, Saif; Adin, Christopher; Kotha, Sainath; Khan, Mahmood; Eubank, Timothy; Scherer, Philipp E.; Parinandi, Narasimham; Magalang, Ulysses J.

    2013-01-01

    Study Objectives: The effects of intermittent hypoxia (IH) on pancreatic function in the presence of diabetes and the underlying mechanisms are unclear. We hypothesized that IH would exacerbate pancreatic β-cell dysfunction and alter the fatty acids in the male Tallyho/JngJ (TH) mouse, a rodent model of type 2 diabetes. Design: TH mice were exposed for 14 d to either 8 h of IH or intermittent air (IA), followed by an intraperitoneal glucose tolerance test (IPGTT) and tissue harvest. The effect of IH on insulin release was determined by using a β3-adrenergic receptor (AR) agonist. Measurements and Results: During IH, pancreatic tissue pO2 decreased from 20.4 ± 0.9 to 5.7 ± 2.6 mm Hg, as determined by electron paramagnetic resonance oximetry. TH mice exposed to IH exhibited higher plasma glucose levels during the IPGTT (P < 0.001) while the insulin levels tended to be lower (P = 0.06). Pancreatic islets of the IH group showed an enhancement of the caspase-3 staining (P = 0.002). IH impaired the β-AR agonist-mediated insulin release (P < 0.001). IH increased the levels of the total free fatty acids and saturated fatty acids (palmitic and stearic acids), and decreased levels of the monounsaturated fatty acids in the pancreas and plasma. Ex vivo exposure of pancreatic islets to palmitic acid suppressed insulin secretion and decreased islet cell viability. Conclusions: Intermittent hypoxia increases pancreatic apoptosis and exacerbates dysfunction in a polygenic rodent model of diabetes. An increase in free fatty acids and a shift in composition towards long chain saturated fatty acid species appear to mediate these effects. Citation: Sherwani SI; Aldana C; Usmani S; Adin C; Kotha S; Khan M; Eubank T; Scherer PE; Parinandi N; Magalang UJ. Intermittent hypoxia exacerbates pancreatic β-cell dysfunction in a mouse model of diabetes mellitus. SLEEP 2013;36(12):1849-1858. PMID:24293759

  20. [Diagnosis and examination for COPD. Pulmonary function tests].

    PubMed

    Kubota, Masaru

    2016-05-01

    Pulmonary function tests are essential for the diagnosis and management of COPD. It is important to understand the inspection method of tests and the interpretation of test results. The presence of a post-bronchodilator FEV1/FVC<0.70 confirms the presence of persistent airflow limitation and the diagnosis of COPD. On the other hand, the classification of severity of airflow limitation in COPD is based on %FEV1. In COPD patients, as airflow limitation worsens gas trapping and static hyperinflation occurs. These changes can be documented by lung volume measurement as increases in functional residual capacity, residual volume and total lung capacity. Measurement of diffusing capacity (DLco) provides information on the functional impact of emphysema in COPD. PMID:27254943

  1. SP-100 nuclear assembly test: Test assembly functional requirements and system arrangement

    NASA Astrophysics Data System (ADS)

    Fallas, T. Ted; Gluck, Robert; Motwani, Kumar; Clay, Harold; O'Neill, Gerald

    1991-01-01

    This paper describes the functional requirements and the system that will be tested to validate the reactor, flight shield, and flight controller of the SP-100 Generic Flight System (GFS). The Nuclear Assembly Test (NAT) consists of the test article (SP-100 reactor with control devices and the flight shield) and its supporting systems. The NAT test assembly is being designed by GE. Westinghouse Hanford Company (WHC) is designing the test cell and vacuum vessel system that will contain the NAT test assembly (Renkey et al. 1989). Preliminary design reviews have been completed and the final design is under way.

  2. Diagnostic Accuracy of a Short Endoscopic Secretin Test in Patients With Cystic Fibrosis

    PubMed Central

    Engjom, Trond; Erchinger, Friedemann; Lærum, Birger Norderud; Tjora, Erling; Aksnes, Lage; Gilja, Odd Helge; Dimcevski, Georg

    2015-01-01

    Objective Short endoscopic secretin tests for exocrine pancreatic function are not properly evaluated in cystic fibrosis (CF). Methods Patients with CF and healthy controls (HCs) underwent endoscopic collection of duodenal juice between 30 and 45 minutes after secretin stimulation. Duodenal juice was analyzed for HCO3− concentration and pancreatic enzyme activities. Stool was analyzed for fecal elastase. Results Thirty-one patients with CF and 25 HCs were tested. Patients were classified as exocrine pancreatic sufficient (n = 13) or insufficient (n = 18). Both bicarbonate concentrations and enzyme activities in duodenal juice differentiated patients with CFI from patients with CFS and HC (P < 0.001). The population displays strong correlation between severe CF genotype in both alleles and pancreatic insufficient phenotype (P < 0.001). Conclusions Pancreatic exocrine insufficient CF patients could be differentiated from exocrine sufficient patients and HCs using short endoscopic secretin test. PMID:26348465

  3. [Problems of lung function testing in the laboratory].

    PubMed

    Tojo, Naoko

    2006-08-01

    Spirometry is indispensable for the screening test of general respiratory function, and measurements of lung volume and diffusing capacity play an important role in the assessment of disease severity, functional disability, disease activity and response to treatment. Pulmonary function testing requires cooperation between the subjects and the examiner, and the results obtained depend on technical as well as personal factors. In order to diminish the variability of results and improve measurement accuracy, the Japan Respiratory Society published the first guidelines on the standardization of spirometry and diffusing capacity for both technical and clinical staff in 2004. It is therefore essential to distribute the guidelines to both laboratory personnel and general physicians. Furthermore, training workshops are mandatory to improve their understanding of the basics of lung function testing. Recently, there has been increasing interest in noninvasive methods of lung function testing without requiring the patient's cooperation during spontaneous breathing. Three alternative techniques, i.e. the negative expiratory pressure (NEP) method to detect expiratory flow limitation, impulse oscillation system (IOS) to measure respiratory system resistance (Rrs) and reactance (Xrs), and interruption resistance (Rint) to measure respiratory resistance have been introduced. Further study is required to determine the advantage of these methods. PMID:16989403

  4. Pulmonary function testing: custom programs for manual equipment.

    PubMed

    Petrini, M F

    1984-01-01

    Pulmonary Function Laboratories with manual equipment can expedite calculations and make them more accurate by using a programmable calculator that will compute functions and predictive equations. However, a custom-made set of programs is better than calculator libraries available from the manufacturer. With custom-made programs, calculations remain as the staff is used to receiving them, programs can be stored in the memory and called independently and only those tests used routinely need to be available. PMID:6546910

  5. Pancreatic insulinomas: Laparoscopic management

    PubMed Central

    Antonakis, Pantelis T; Ashrafian, Hutan; Martinez-Isla, Alberto

    2015-01-01

    Insulinomas are rare pancreatic neuroendocrine tumors that are most commonly benign, solitary, and intrapancreatic. Uncontrolled insulin overproduction from the tumor produces neurological and adrenergic symptoms of hypoglycemia. Biochemical diagnosis is confirmed by the presence of Whipple’s triad, along with corroborating measurements of blood glucose, insulin, proinsulin, C-peptide, β-hydroxybutyrate, and negative tests for hypoglycemic agents during a supervised fasting period. This is accompanied by accurate preoperative localization using both invasive and non-invasive imaging modalities. Following this, careful preoperative planning is required, with the ensuing procedure being preferably carried out laparoscopically. An integral part of the laparoscopic approach is the application of laparoscopic intraoperative ultrasound, which is indispensable for accurate intraoperative localization of the lesion in the pancreatic region. The extent of laparoscopic resection is dependent on preoperative and intraoperative findings, but most commonly involves tumor enucleation or distal pancreatectomy. When performed in an experienced surgical unit, laparoscopic resection is associated with minimal mortality and excellent long-term cure rates. Furthermore, this approach confers equivalent safety and efficacy rates to open resection, while improving cosmesis and reducing hospital stay. As such, laparoscopic resection should be considered in all cases of benign insulinoma where adequate surgical expertise is available. PMID:26566426

  6. Outcomes of Anatomical versus Functional Testing for Coronary Artery Disease

    PubMed Central

    Douglas, Pamela S.; Hoffmann, Udo; Patel, Manesh R.; Mark, Daniel B.; Al-Khalidi, Hussein R.; Cavanaugh, Brendan; Cole, Jason; Dolor, Rowena J.; Fordyce, Christopher B.; Huang, Megan; Khan, Muhammad Akram; Kosinski, Andrzej S.; Krucoff, Mitchell W.; Malhotra, Vinay; Picard, Michael H.; Udelson, James E.; Velazquez, Eric J.; Yow, Eric; Cooper, Lawton S.; Lee, Kerry L.

    2015-01-01

    BACKGROUND Many patients have symptoms suggestive of coronary artery disease (CAD) and are often evaluated with the use of diagnostic testing, although there are limited data from randomized trials to guide care. METHODS We randomly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography (CTA) or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography). The composite primary end point was death, myocardial infarction, hospitalization for unstable angina, or major procedural complication. Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure. RESULTS The mean age of the patients was 60.8±8.3 years, 52.7% were women, and 87.7% had chest pain or dyspnea on exertion. The mean pretest likelihood of obstructive CAD was 53.3±21.4%. Over a median follow-up period of 25 months, a primary end-point event occurred in 164 of 4996 patients in the CTA group (3.3%) and in 151 of 5007 (3.0%) in the functional-testing group (adjusted hazard ratio, 1.04; 95% confidence interval, 0.83 to 1.29; P = 0.75). CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing (3.4% vs. 4.3%, P = 0.02), although more patients in the CTA group underwent catheterization within 90 days after randomization (12.2% vs. 8.1%). The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group (10.0 mSv vs. 11.3 mSv), but 32.6% of the patients in the functional-testing group had no exposure, so the overall exposure was higher in the CTA group (mean, 12.0 mSv vs. 10.1 mSv; P<0.001). CONCLUSIONS In symptomatic patients with suspected CAD who required noninvasive testing, a strategy of initial CTA, as compared with functional testing, did not improve clinical outcomes over a median follow-up of 2 years. (Funded by the

  7. Endoscopic treatment of pancreatic calculi.

    PubMed

    Kim, Yong Hoon; Jang, Sung Ill; Rhee, Kwangwon; Lee, Dong Ki

    2014-05-01

    Chronic pancreatitis is a progressive inflammatory disease that destroys pancreatic parenchyma and alters ductal stricture, leading to ductal destruction and abdominal pain. Pancreatic duct stones (PDSs) are a common complication of chronic pancreatitis that requires treatment to relieve abdominal pain and improve pancreas function. Endoscopic therapy, extracorporeal shock wave lithotripsy (ESWL), and surgery are treatment modalities of PDSs, although lingering controversies have hindered a consensus recommendation. Many comparative studies have reported that surgery is the superior treatment because of reduced duration and frequency of hospitalization, cost, pain relief, and reintervention, while endoscopic therapy is effective and less invasive but cannot be used in all patients. Surgery is the treatment of choice when endoscopic therapy has failed, malignancy is suspected, or duodenal stricture is present. However, in patients with the appropriate indications or at high-risk for surgery, endoscopic therapy in combination with ESWL can be considered a first-line treatment. We expect that the development of advanced endoscopic techniques and equipment will expand the role of endoscopic treatment in PDS removal. PMID:24944986

  8. Repeated mobility testing for later artificial visual function evaluation

    NASA Astrophysics Data System (ADS)

    Velikay-Parel, M.; Ivastinovic, D.; Koch, M.; Hornig, R.; Dagnelie, G.; Richard, G.; Langmann, A.

    2007-03-01

    The study investigates the utility of a newly designed mobility test for repeated testing of visual function in patients with severe visual impairment and future application in evaluating functional progress in patients with artificial vision. Ten subjects divided into three groups based on visual acuity (VA) ranging from light perception to 20/200 and reduced visual field (VF) were included in the study. The mobility test consisted of using a set of four different but structurally similar and relatively short mazes having a constant number of obstacles of various sizes. The subjects, divided into three groups by acuity, passed through each course several times. In general, the patients with better VA had a larger extent of VF. Average speed and number of contacts were recorded as measures of performance. The average passing times of the groups through the courses were significantly different (p = 0.03), which was influenced by VA and VF. There was no significant difference in average number of contacts between the groups (p = 0.15). The mobility test proved to be appropriate for gaining statistically relevant results in repeated individual testing of patients with severe vision impairment. Results show promise for use this mobility test as a tool for assessing visual function of patients undergoing implantation of a visual prosthesis for artificial vision.

  9. GROUND-WATER MODEL TESTING: SYSTEMATIC EVALUATION AND TESTING OF CODE FUNCTIONALITY AND PERFORMANCE

    EPA Science Inventory

    Effective use of ground-water simulation codes as management decision tools requires the establishment of their functionality, performance characteristics, and applicability to the problem at hand. This is accomplished through application of a systematic code-testing protocol and...

  10. Dimethyl Fumarate Protects Pancreatic Islet Cells and Non-Endocrine Tissue in L-Arginine-Induced Chronic Pancreatitis

    PubMed Central

    Robles, Lourdes; Vaziri, Nosratola D.; Li, Shiri; Masuda, Yuichi; Takasu, Chie; Takasu, Mizuki; Vo, Kelly; Farzaneh, Seyed H.; Stamos, Michael J.; Ichii, Hirohito

    2014-01-01

    Background Chronic pancreatitis (CP) is a progressive disorder resulting in the destruction and fibrosis of the pancreatic parenchyma which ultimately leads to impairment of the endocrine and exocrine functions. Dimethyl Fumarate (DMF) was recently approved by FDA for treatment of patients with multiple sclerosis. DMF's unique anti-oxidant and anti-inflammatory properties make it an interesting drug to test on other inflammatory conditions. This study was undertaken to determine the effects of DMF on islet cells and non-endocrine tissue in a rodent model of L-Arginine-induced CP. Methods Male Wistar rats fed daily DMF (25 mg/kg) or vehicle by oral gavage were given 5 IP injections of L-Arginine (250 mg/100 g×2, 1 hr apart). Rats were assessed with weights and intra-peritoneal glucose tolerance tests (IPGTT, 2 g/kg). Islets were isolated and assessed for islet mass and viability with flow cytometry. Non-endocrine tissue was assessed for histology, myeloperoxidase (MPO), and lipid peroxidation level (MDA). In vitro assessments included determination of heme oxygenase (HO-1) protein expression by Western blot. Results Weight gain was significantly reduced in untreated CP group at 6 weeks. IPGTT revealed significant impairment in untreated CP group and its restoration with DMF therapy (P <0.05). Untreated CP rats had pancreatic atrophy, severe acinar architectural damage, edema, and fatty infiltration as well as elevated MDA and MPO levels, which were significantly improved by DMF treatment. After islet isolation, the volume of non-endocrine tissue was significantly smaller in untreated CP group. Although islet counts were similar in the two groups, islet viability was significantly reduced in untreated CP group and improved with DMF treatment. In vitro incubation of human pancreatic tissue with DMF significantly increased HO-1 expression. Conclusion Administration of DMF attenuated L-Arginine-induced CP and islet function in rats. DMF treatment could be a possible

  11. Metformin inhibits cell proliferation, migration and invasion by attenuating CSC function mediated by deregulating miRNAs in pancreatic cancer cells.

    PubMed

    Bao, Bin; Wang, Zhiwei; Ali, Shadan; Ahmad, Aamir; Azmi, Asfar S; Sarkar, Sanila H; Banerjee, Sanjeev; Kong, Dejuan; Li, Yiwei; Thakur, Shivam; Sarkar, Fazlul H

    2012-03-01

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States, which is, in part, due to intrinsic (de novo) and extrinsic (acquired) resistance to conventional therapeutics, suggesting that innovative treatment strategies are required for overcoming therapeutic resistance to improve overall survival of patients. Oral administration of metformin in patients with diabetes mellitus has been reported to be associated with reduced risk of pancreatic cancer and that metformin has been reported to kill cancer stem cells (CSC); however, the exact molecular mechanism(s) has not been fully elucidated. In the current study, we examined the effect of metformin on cell proliferation, cell migration and invasion, and self-renewal capacity of CSCs and further assessed the expression of CSC marker genes and microRNAs (miRNA) in human pancreatic cancer cells. We found that metformin significantly decreased cell survival, clonogenicity, wound-healing capacity, sphere-forming capacity (pancreatospheres), and increased disintegration of pancreatospheres in both gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cells. Metformin also decreased the expression of CSC markers,CD44, EpCAM,EZH2, Notch-1, Nanog and Oct4, and caused reexpression of miRNAs (let-7a,let-7b, miR-26a, miR-101, miR-200b, and miR-200c) that are typically lost in pancreatic cancer and especially in pancreatospheres. We also found that reexpression of miR-26a by transfection led to decreased expression of EZH2 and EpCAM in pancreatic cancer cells. These results clearly suggest that the biologic effects of metformin are mediated through reexpression of miRNAs and decreased expression of CSC-specific genes, suggesting that metformin could be useful for overcoming therapeutic resistance of pancreatic cancer cells. PMID:22086681

  12. [Eosin Y-water test for sperm function examination].

    PubMed

    Zha, Shu-wei; Lü, Nian-qing; Xu, Hao-qin

    2015-06-01

    Based on the principles of the in vitro staining technique, hypotonic swelling test, and water test, the Eosin Y-water test method was developed to simultaneously detect the integrity of the sperm head and tail and sperm membrane structure and function. As a widely used method in clinical laboratories in China, the Eosin Y-water test is methodologically characterized by three advantages. Firstly, both the sperm head and tail can be detected at the same time, which allows easy and comprehensive assessment of membrane damage in different parts of sperm. Secondly, distilled water is used instead of the usual formula solution to simplify and standardize the test by eliminating any potential effects on the water molecules through the sperm membrane due to different osmotic pressure or different sugar proportions and electrolyte solutions. Thirdly, the test takes less time and thus can be repeated before and after treatment. This article focuses on the fundamental principles and modification of the Eosin Y-water test and its application in sperm function examination and routine semen analysis for male infertility, assessment of the quality of sperm retrieved by testicular fine needle aspiration, semen cryopreservation program development, and evaluation of sperm membrane integrity after microwave radiation. PMID:26242051

  13. The Functional Task Test (FTT): An Interdisciplinary Testing Protocol to Investigate the Factors Underlying Changes in Astronaut Functional Performance

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Lawrence, E. L.; Arzeno, N. M.; Buxton, R. E.; Feiveson, A. H.; Kofman, I. S.; Lee, S. M. C.; Mulavara, A. P.; Peters, B. T.; Platts. S. H.; Ploutz-Snyder, L. L.; Reschke, M. F.; Ryder, J. W.; Spiering, B. A.; Stenger, M. B.; Taylor, L. C.; Wood, S. J.

    2011-01-01

    Exposure to space flight causes adaptations in multiple physiological systems including changes in sensorimotor, cardiovascular, and neuromuscular systems. These changes may affect a crewmember s ability to perform critical mission tasks immediately after landing on a planetary surface. The overall goal of this project is to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. To achieve this goal we developed an interdisciplinary testing protocol (Functional Task Test, FTT) that evaluates both astronaut functional performance and related physiological changes. Functional tests include ladder climbing, hatch opening, jump down, manual manipulation of objects and tool use, seat egress and obstacle avoidance, recovery from a fall and object translation tasks. Physiological measures include assessments of postural and gait control, dynamic visual acuity, fine motor control, plasma volume, orthostatic intolerance, upper- and lower-body muscle strength, power, endurance, control, and neuromuscular drive. Crewmembers perform this integrated test protocol before and after short (Shuttle) and long-duration (ISS) space flight. Data are collected on two sessions before flight, on landing day (Shuttle only) and 1, 6 and 30 days after landing. Preliminary results from both Shuttle and ISS crewmembers indicate decrement in performance of the functional tasks after both short and long-duration space flight. On-going data collection continues to improve the statistical power required to map changes in functional task performance to alterations in physiological systems. The information obtained from this study will be used to design and implement countermeasures that specifically target the physiological systems most responsible for the altered functional performance associated with space flight.

  14. Fibrocalculous pancreatic diabetes.

    PubMed

    Goundan, Poorani; Junqueira, Ana; Kelleher-Yassen, Donna; Steenkamp, Devin

    2016-03-01

    The aim of this paper is to review the relevant literature related to the epidemiology, pathophysiology, natural history, clinical features and treatment of fibrocalculous pancreatic diabetes (FCPD). We review the English-language literature on this topic published between 1956 and 2014. FCPD is a form of diabetes usually associated with chronic calcific pancreatitis. It has been predominantly, though not exclusively, described in lean, young adults living in tropical developing countries. Historically linked to malnutrition, the etiology of this phenotype has not been clearly elucidated, nor has there been a clear consensus on specific diagnostic criteria or clinical features. Affected individuals usually present with a long-standing history of abdominal pain, which may begin as early as childhood. Progressive pancreatic endocrine and exocrine dysfunction, consistent with chronic pancreatitis is expected. Common causes of chronic pancreatitis, such as alcohol abuse, are usually absent. Typical radiographic and pathological features include coarse pancreatic calcifications, main pancreatic duct dilation, pancreatic fibrosis and atrophy. Progressive microvascular complications are common, but diabetic ketoacidosis is remarkably unusual. Pancreatic carcinoma is an infrequently described long term complication. FCPD is an uncommon diabetes phenotype characterized by early onset non-alcoholic chronic pancreatitis with hyperglycemia, insulin deficiency and a striking resistance to ketosis. PMID:26472503

  15. Frequency importance functions for a feature recognition test material.

    PubMed

    Duggirala, V; Studebaker, G A; Pavlovic, C V; Sherbecoe, R L

    1988-06-01

    The relative importance of different parts of the auditory spectrum to recognition of the Diagnostic Rhyme Test (DRT) and its six speech feature subtests was determined. Three normal hearing subjects were tested twice in each of 70 experimental conditions. The analytical procedures of French and Steinberg [J. Acoust. Soc. Am. 19, 90-119 (1947)] were applied to the data to derive frequency importance functions for each of the DRT subtests and the test as a whole over the frequency range 178-8912 Hz. For the DRT as a whole, the low frequencies were found to be more important than is the case for nonsense syllables. Importance functions for the feature subtests also differed from those for nonsense syllables and from each other as well. These results suggest that test materials loaded with different proportions of particular phonemes have different frequency importance functions. Comparison of the results with those from other studies suggests that importance functions depend to a degree on the available response options as well. PMID:3411027

  16. Executive Function in Preschool Children: Test-Retest Reliability

    ERIC Educational Resources Information Center

    Beck, Danielle M.; Schaefer, Catherine; Pang, Karen; Carlson, Stephanie M.

    2011-01-01

    Research suggests that executive function (EF) may distinguish between children who are well- or ill-prepared for kindergarten; however, little is known about the test-retest reliability of measures of EF for children. We aimed to establish a battery of EF measures that are sensitive to both development and individual differences across the…

  17. Testing for Differential Item Functioning with Measures of Partial Association

    ERIC Educational Resources Information Center

    Woods, Carol M.

    2009-01-01

    Differential item functioning (DIF) occurs when an item on a test or questionnaire has different measurement properties for one group of people versus another, irrespective of mean differences on the construct. There are many methods available for DIF assessment. The present article is focused on indices of partial association. A family of average…

  18. Advances in the Detection of Differentially Functioning Test Items.

    ERIC Educational Resources Information Center

    Hambleton, Ronald K.; And Others

    The development and evaluation of methods for detecting potentially biased items or differentially functioning items (DIF) represent a critical area of research for psychometricians because of the negative impact of biased items on test validity. A summary is provided of the authors' 12 years of research at the University of Massachusetts…

  19. Testing anatomically specified hypotheses in functional imaging using cytoarchitectonic maps.

    PubMed

    Eickhoff, Simon B; Heim, Stefan; Zilles, Karl; Amunts, Katrin

    2006-08-15

    The statistical inference on functional imaging data is severely complicated by the embedded multiple testing problem. Defining a region of interest (ROI) where the activation is hypothesized a priori helps to circumvent this problem, since in this case the inference is restricted to fewer simultaneous tests, rendering it more sensitive. Cytoarchitectonic maps obtained from postmortem brains provide objective, a priori ROIs that can be used to test anatomically specified hypotheses about the localization of functional activations. We here analyzed three methods for the definition of ROIs based on probabilistic cytoarchitectonic maps. (1) ROIs defined by the volume assigned to a cytoarchitectonic area in the summary map of all areas (maximum probability map, MPM), (2) ROIs based on thresholding the individual probabilistic maps and (3) spherical ROIs build around the cytoarchitectonic center of gravity. The quality with which the thus defined ROIs represented the respective cytoarchitectonic areas as well as their sensitivity for detecting functional activations was subsequently statistically evaluated. Our data showed that the MPM method yields ROIs, which reflect most adequately the underlying anatomical hypotheses. These maps also show a high degree of sensitivity in the statistical analysis. We thus propose the use of MPMs for the definition of ROIs. In combination with thresholding based on the Gaussian random field theory, these ROIs can then be applied to test anatomically specified hypotheses in functional neuroimaging studies. PMID:16781166

  20. Carboxyl-terminal domain of MUC16 imparts tumorigenic and metastatic functions through nuclear translocation of JAK2 to pancreatic cancer cells

    PubMed Central

    Das, Srustidhar; Lakshmanan, Imayavaramban; Majhi, Prabin D.; Smith, Lynette M.; Wagner, Kay-Uwe; Batra, Surinder K.

    2015-01-01

    MUC16 (CA125) is a type-I transmembrane glycoprotein that is up-regulated in multiple cancers including pancreatic cancer (PC). However, the existence and role of carboxyl-terminal MUC16 generated following its cleavage in PC is unknown. Our previous study using a systematic dual-epitope tagged domain deletion approach of carboxyl-terminal MUC16 has demonstrated the generation of a 17-kDa cleaved MUC16 (MUC16-Cter). Here, we demonstrate the functional significance of MUC16-Cter in PC using the dual-epitope tagged version (N-terminal FLAG- and C-terminal HA-tag) of 114 carboxyl-terminal residues of MUC16 (F114HA). In vitro analyses using F114HA transfected MiaPaCa-2 and T3M4 cells showed enhanced proliferation, motility and increased accumulation of cells in the G2/M phase with apoptosis resistance, a feature associated with cancer stem cells (CSCs). This was supported by enrichment of ALDH+ CSCs along with enhanced drug-resistance. Mechanistically, we demonstrate a novel function of MUC16-Cter that promotes nuclear translocation of JAK2 resulting in phosphorylation of Histone-3 up-regulating stemness-specific genes LMO2 and NANOG. Jak2 dependence was demonstrated using Jak2+/+ and Jak2−/− cells. Using eGFP-Luciferase labeled cells, we demonstrate enhanced tumorigenic and metastatic potential of MUC16-Cter in vivo. Taken together, we demonstrate that MUC16-Cter mediated enrichment of CSCs is partly responsible for tumorigenic, metastatic and drug-resistant properties of PC cells. PMID:25691062

  1. Progesterone Receptor Membrane Component 1 Is a Functional Part of the Glucagon-like Peptide-1 (GLP-1) Receptor Complex in Pancreatic β Cells*

    PubMed Central

    Zhang, Ming; Robitaille, Mélanie; Showalter, Aaron D.; Huang, Xinyi; Liu, Ying; Bhattacharjee, Alpana; Willard, Francis S.; Han, Junfeng; Froese, Sean; Wei, Li; Gaisano, Herbert Y.; Angers, Stéphane; Sloop, Kyle W.; Dai, Feihan F.; Wheeler, Michael B.

    2014-01-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates glucose homeostasis. Because of their direct stimulation of insulin secretion from pancreatic β cells, GLP-1 receptor (GLP-1R) agonists are now important therapeutic options for the treatment of type 2 diabetes. To better understand the mechanisms that control the insulinotropic actions of GLP-1, affinity purification and mass spectrometry (AP-MS) were employed to uncover potential proteins that functionally interact with the GLP-1R. AP-MS performed on Chinese hamster ovary cells or MIN6 β cells, both expressing the human GLP-1R, revealed 99 proteins potentially associated with the GLP-1R. Three novel GLP-1R interactors (PGRMC1, Rab5b, and Rab5c) were further validated through co-immunoprecipitation/immunoblotting, fluorescence resonance energy transfer, and immunofluorescence. Functional studies revealed that overexpression of PGRMC1, a novel cell surface receptor that associated with liganded GLP-1R, enhanced GLP-1-induced insulin secretion (GIIS) with the most robust effect. Knockdown of PGRMC1 in β cells decreased GIIS, indicative of positive interaction with GLP-1R. To gain insight mechanistically, we demonstrated that the cell surface PGRMC1 ligand P4-BSA increased GIIS, whereas its antagonist AG-205 decreased GIIS. It was then found that PGRMC1 increased GLP-1-induced cAMP accumulation. PGRMC1 activation and GIIS induced by P4-BSA could be blocked by inhibition of adenylyl cyclase/EPAC signaling or the EGF receptor–PI3K signal transduction pathway. These data reveal a dual mechanism for PGRMC1-increased GIIS mediated through cAMP and EGF receptor signaling. In conclusion, we identified several novel GLP-1R interacting proteins. PGRMC1 expressed on the cell surface of β cells was shown to interact with the activated GLP-1R to enhance the insulinotropic actions of GLP-1. PMID:25044020

  2. Using Operational Analysis to Improve Access to Pulmonary Function Testing.

    PubMed

    Ip, Ada; Asamoah-Barnieh, Raymond; Bischak, Diane P; Davidson, Warren J; Flemons, W Ward; Pendharkar, Sachin R

    2016-01-01

    Background. Timely pulmonary function testing is crucial to improving diagnosis and treatment of pulmonary diseases. Perceptions of poor access at an academic pulmonary function laboratory prompted analysis of system demand and capacity to identify factors contributing to poor access. Methods. Surveys and interviews identified stakeholder perspectives on operational processes and access challenges. Retrospective data on testing demand and resource capacity was analyzed to understand utilization of testing resources. Results. Qualitative analysis demonstrated that stakeholder groups had discrepant views on access and capacity in the laboratory. Mean daily resource utilization was 0.64 (SD 0.15), with monthly average utilization consistently less than 0.75. Reserved testing slots for subspecialty clinics were poorly utilized, leaving many testing slots unfilled. When subspecialty demand exceeded number of reserved slots, there was sufficient capacity in the pulmonary function schedule to accommodate added demand. Findings were shared with stakeholders and influenced scheduling process improvements. Conclusion. This study highlights the importance of operational data to identify causes of poor access, guide system decision-making, and determine effects of improvement initiatives in a variety of healthcare settings. Importantly, simple operational analysis can help to improve efficiency of health systems with little or no added financial investment. PMID:27445545

  3. Using Operational Analysis to Improve Access to Pulmonary Function Testing

    PubMed Central

    Ip, Ada; Asamoah-Barnieh, Raymond; Bischak, Diane P.; Davidson, Warren J.; Flemons, W. Ward; Pendharkar, Sachin R.

    2016-01-01

    Background. Timely pulmonary function testing is crucial to improving diagnosis and treatment of pulmonary diseases. Perceptions of poor access at an academic pulmonary function laboratory prompted analysis of system demand and capacity to identify factors contributing to poor access. Methods. Surveys and interviews identified stakeholder perspectives on operational processes and access challenges. Retrospective data on testing demand and resource capacity was analyzed to understand utilization of testing resources. Results. Qualitative analysis demonstrated that stakeholder groups had discrepant views on access and capacity in the laboratory. Mean daily resource utilization was 0.64 (SD 0.15), with monthly average utilization consistently less than 0.75. Reserved testing slots for subspecialty clinics were poorly utilized, leaving many testing slots unfilled. When subspecialty demand exceeded number of reserved slots, there was sufficient capacity in the pulmonary function schedule to accommodate added demand. Findings were shared with stakeholders and influenced scheduling process improvements. Conclusion. This study highlights the importance of operational data to identify causes of poor access, guide system decision-making, and determine effects of improvement initiatives in a variety of healthcare settings. Importantly, simple operational analysis can help to improve efficiency of health systems with little or no added financial investment. PMID:27445545

  4. Drugs Approved for Pancreatic Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Pancreatic Cancer This page lists cancer ... in pancreatic cancer that are not listed here. Drugs Approved for Pancreatic Cancer Abraxane (Paclitaxel Albumin-stabilized ...

  5. Pancreatic Cancer Stage 2B

    MedlinePlus

    ... 2B Description: Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum. Stage IIB pancreatic cancer. Cancer has spread to nearby lymph nodes and ...

  6. Pancreatic Cancer Stage 2A

    MedlinePlus

    ... 2A Description: Stage IIA pancreatic cancer; drawing shows cancer in the pancreas and duodenum. The bile duct and pancreatic duct are also shown. Stage IIA pancreatic cancer. Cancer has spread to nearby tissue and organs ...

  7. The Importance of Functional Tests in Personalized Medicine

    PubMed Central

    Widmer, R. Jay; Lerman, Amir

    2013-01-01

    Cardiovascular disease is the most prevalent disease mainly in the Western society and becoming the leading cause of death worldwide. Standard methods by which healthcare providers screen for cardiovascular disease have only minimally reduced the burden of disease while exponentially increasing costs. As such, more specific and individualized methods for functionally assessing cardiovascular threats are needed to identify properly those at greatest risk, and appropriately treat these patients so as to avoid a fate such as heart attack, stroke, or death. Currently, endothelial function testing—in both the coronary and peripheral circulation—is well established as being associated with the disease process and future cardiovascular events. Improving such testing can lead to a reduction in the risk of future events. Combining this functional assessment of vascular fitness with other, more personalized, testing methods should serve to identify those at the greatest risk of cardiovascular disease earlier and subsequently reduce the affliction of such diseases worldwide. PMID:23908864

  8. Transpapillary biliary stenting is a risk factor for pancreatic stones in patients with autoimmune pancreatitis

    PubMed Central

    Matsubayashi, Hiroyuki; Kishida, Yoshihiro; Iwai, Tomohiro; Murai, Katsuyuki; Yoshida, Masao; Imai, Kenichiro; Yamamoto, Yusuke; Kikuyama, Masataka; Ono, Hiroyuki

    2016-01-01

    Background and study aim: Pancreatic stones occasionally develop in autoimmune pancreatitis (AIP), often worsen endocrine and exocrine functions, and occasionally cause pain attacks. However, the risks of pancreatic stones in AIP have been poorly studied. The aim of this study was to analyze the risk factors associated with pancreatic stone formation in cases of AIP. Patients and methods: In total, 50 patients with AIP (39 males, 11 females; mean age 64.0 years), followed up for at least a year, were analyzed for their demographic and clinical findings and pancreatic stone occurrence. Results: In total, 50 patients were followed up for an average of 59.7 (12 – 120) months, with steroid treatment in 44 patients (88 %); pancreatic stones occurred in 14 (28 %) patients after the diagnosis of AIP and endoscopic treatment was needed in one patient with pain attack. The pancreatic stones appeared only in patients with long follow-up period (P < 0.001, 83.9 months vs. 49.6 months), biliary stenting (odds ratio [OR]: 8.40, P = 0.010), relapse (OR: 6.20, P = 0.023), jaundice (OR: 5.40, P = 0.019), and swelling of the duodenal major papilla (OR: 4.67, P = 0.040). Biliary stenting was placed for an average of 9.9 months in 27 patients. Multivariate analysis revealed a significant association only with biliary stenting (P = 0.011). The stones appeared relatively earlier in patients with stones in the main pancreatic duct or Santorini duct (22.1 months) than in patients where pancreatic stones developed elsewhere (53.4 months) (P = 0.018). Conclusions: The risk of pancreatic stone development should be taken into account when a biliary stent is placed in patients with AIP. PMID:27540582

  9. Insulin secretion as a determinant of pancreatic cancer risk.

    PubMed

    McCarty, M F

    2001-08-01

    New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. PMID:11461162

  10. Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells.

    PubMed

    Asalla, Suman; Girada, Shravan Babu; Kuna, Ramya S; Chowdhury, Debabrata; Kandagatla, Bhaskar; Oruganti, Srinivas; Bhadra, Utpal; Bhadra, Manika Pal; Kalivendi, Shasi Vardhan; Rao, Swetha Pavani; Row, Anupama; Ibrahim, A; Ghosh, Partha Pratim; Mitra, Prasenjit

    2016-01-01

    Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation. PMID:27282931

  11. Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells

    PubMed Central

    Asalla, Suman; Girada, Shravan Babu; Kuna, Ramya S.; Chowdhury, Debabrata; Kandagatla, Bhaskar; Oruganti, Srinivas; Bhadra, Utpal; Bhadra, Manika Pal; Kalivendi, Shasi Vardhan; Rao, Swetha Pavani; Row, Anupama; Ibrahim, A; Ghosh, Partha Pratim; Mitra, Prasenjit

    2016-01-01

    Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation. PMID:27282931

  12. Multiple-Group Noncompensatory Differential Item Functioning in Raju's Differential Functioning of Items and Tests

    ERIC Educational Resources Information Center

    Oshima, T. C.; Wright, Keith; White, Nick

    2015-01-01

    Raju, van der Linden, and Fleer (1995) introduced a framework for differential functioning of items and tests (DFIT) for unidimensional dichotomous models. Since then, DFIT has been shown to be a quite versatile framework as it can handle polytomous as well as multidimensional models both at the item and test levels. However, DFIT is still limited…

  13. Pancreatic cancer cachexia: a review of mechanisms and therapeutics

    PubMed Central

    Tan, Carlyn R.; Yaffee, Patrick M.; Jamil, Laith H.; Lo, Simon K.; Nissen, Nicholas; Pandol, Stephen J.; Tuli, Richard; Hendifar, Andrew E.

    2014-01-01

    Over the last decade, we have gained new insight into the pathophysiology of cachexia associated with pancreatic cancer. Unfortunately, its treatment is complex and remains a challenge. Pancreatic cancer cachexia is a multifactorial syndrome characterized by uncompensated adipose tissue and skeletal muscle loss in the setting of anorexia that leads to progressive functional impairment. This paper will review the current concepts of pancreatic cancer cachexia, its assessment and pathophysiology as well as current and future treatments. The successful management of pancreatic cancer cachexia will likely require a multimodal approach that includes nutritional support and combination pharmaceutical interventions. PMID:24624094

  14. Synergistic Role of TRPV1 and TRPA1 in Pancreatic Pain and Inflammation

    PubMed Central

    Schwartz, Erica S.; Christianson, Julie A.; Chen, Xiaowei; La, Jun-Ho; Davis, Brian M.; Albers, Kathryn M.; Gebhart, G.F.

    2011-01-01

    Background & Aims The transient receptor potential (TRP) channels TRPV1 and TRPA1 have each been associated with regulation of efferent properties of primary afferent neurons that initiate neurogenic inflammation and are required for the development of inflammatory hyperalgesia. To evaluate the role of these channels in producing pain during pancreatic inflammation, we studied pancreatic nodose (NG) and dorsal root (DRG) ganglion sensory neurons (identified by content of retrograde tracer) and behavioral outcomes in a mouse model of acute pancreatitis. Methods Pancreatic inflammation was induced by 8 hourly injections of caerulein (50 μg/kg). The extent of inflammation, pancreatic neuron TRP channel expression and function and excitability, and pain-related behaviors were evaluated over the course of the following week. Results Histology and myeloperoxidase activity confirmed pancreatic inflammation that was associated with increased excitability and mRNA expression of the TRP channels in NG and DRG pancreatic neurons. Calcium imaging of pancreatic NG and DRG neurons from mice given caerulein revealed increased responses to TRP agonists. TRPV1 and TRPA1 antagonists attenuated caerulein-induced pain behaviors and pancreatic inflammation; they had a synergistic effect. Conclusions Pancreatic inflammation significantly increased the expression and functional properties of TRPV1 and TRPA1, as well as the excitability of pancreatic sensory neurons in vagal and spinal pathways. TRP channel antagonists acted synergistically to reverse pancreatic inflammation and associated pain behaviors; reagents that target interactions between these channels might be developed to reduce pain in patients with acute pancreatitis. PMID:21185837

  15. Pancreatic and biliary secretion are both altered in cystic fibrosis pigs

    PubMed Central

    Giriyappa, Radhamma; Meyerholz, David K.; Griffin, Michelle; Ostedgaard, Lynda S.; Tang, Xiao Xiao; Abu-El-Haija, Marwa; Stoltz, David A.; Ludwig, Paula; Pezzulo, Alejandro; Abu-El-Haija, Maisam; Taft, Peter; Welsh, Michael J.

    2012-01-01

    The pancreas, liver, and gallbladder are commonly involved in cystic fibrosis (CF), and acidic, dehydrated, and protein-rich secretions are characteristic findings. Pancreatic function studies in humans have been done by sampling the jejunal fluid. However, it has been difficult to separately study the function of pancreatic and biliary systems in humans with CF, because jejunal fluid contains a mixture of bile and pancreatic fluids. In contrast, pancreatic and biliary ducts open separately into the porcine intestine; therefore, biliary and pancreatic fluid can be individually analyzed in CF pigs. We studied newborn wild-type (WT) and CF pigs and found that CFTR was localized to the pancreatic ducts. We collected bile and pancreatic fluid and analyzed pancreatic enzymes with activity assays and immunoblot. Pancreatic enzyme expression was significantly decreased in CF compared with WT pigs. The volume and pH of pancreatic fluid were significantly lower and protein concentration was >5-fold higher in CF pigs. Secretin stimulation increased pancreatic fluid volume and pH in WT, but not CF, pigs. Baseline bile volume did not differ between WT and CF pigs, but volume did not increase in response to secretin in CF pigs. Bile pH was lower and protein concentration was twofold higher in CF pigs. These results indicate that pancreatic and biliary secretions are altered in CF pigs. Abnormal pancreatic and biliary secretion in CF may have important implications in disease pathogenesis. PMID:22936270

  16. Pancreatic and biliary secretion are both altered in cystic fibrosis pigs.

    PubMed

    Uc, Aliye; Giriyappa, Radhamma; Meyerholz, David K; Griffin, Michelle; Ostedgaard, Lynda S; Tang, Xiao Xiao; Abu-El-Haija, Marwa; Stoltz, David A; Ludwig, Paula; Pezzulo, Alejandro; Abu-El-Haija, Maisam; Taft, Peter; Welsh, Michael J

    2012-10-15

    The pancreas, liver, and gallbladder are commonly involved in cystic fibrosis (CF), and acidic, dehydrated, and protein-rich secretions are characteristic findings. Pancreatic function studies in humans have been done by sampling the jejunal fluid. However, it has been difficult to separately study the function of pancreatic and biliary systems in humans with CF, because jejunal fluid contains a mixture of bile and pancreatic fluids. In contrast, pancreatic and biliary ducts open separately into the porcine intestine; therefore, biliary and pancreatic fluid can be individually analyzed in CF pigs. We studied newborn wild-type (WT) and CF pigs and found that CFTR was localized to the pancreatic ducts. We collected bile and pancreatic fluid and analyzed pancreatic enzymes with activity assays and immunoblot. Pancreatic enzyme expression was significantly decreased in CF compared with WT pigs. The volume and pH of pancreatic fluid were significantly lower and protein concentration was >5-fold higher in CF pigs. Secretin stimulation increased pancreatic fluid volume and pH in WT, but not CF, pigs. Baseline bile volume did not differ between WT and CF pigs, but volume did not increase in response to secretin in CF pigs. Bile pH was lower and protein concentration was twofold higher in CF pigs. These results indicate that pancreatic and biliary secretions are altered in CF pigs. Abnormal pancreatic and biliary secretion in CF may have important implications in disease pathogenesis. PMID:22936270

  17. Consensus Recommendations for the Diagnosis and Management of Pancreatic Neuroendocrine Tumors: Guidelines from a Canadian National Expert Group.

    PubMed

    Singh, Simron; Dey, Chris; Kennecke, Hagen; Kocha, Walter; Maroun, Jean; Metrakos, Peter; Mukhtar, Tariq; Pasieka, Janice; Rayson, Daniel; Rowsell, Corwyn; Sideris, Lucas; Wong, Ralph; Law, Calvin

    2015-08-01

    Pancreatic neuroendocrine tumors (pNETs) are rare heterogeneous tumors that have been steadily increasing in both incidence and prevalence during the past few decades. Pancreatic NETs are categorized as functional (F) or nonfunctional (NF) based on their ability to secrete hormones that elicit clinically relevant symptoms. Specialized diagnostic tests are required for diagnosis. Treatment options are diverse and include surgical resection, intraarterial hepatic therapy, and peptide receptor radionuclide therapy (PRRT). Systemic therapy options include targeted agents as well as chemotherapy when indicated. Diagnosis and management should occur through a collaborative team of health care practitioners well-experienced in managing pNETs. Recent advances in pNET treatment options have led to the development of the Canadian consensus document described in this report. The discussion includes the epidemiology, classification, pathology, clinical presentation and prognosis, imaging and laboratory testing, medical and surgical management, and recommended treatment algorithms for pancreatic neuroendocrine cancers. PMID:25366583

  18. Molecular Diagnostics in the Evaluation of Pancreatic Cysts.

    PubMed

    Theisen, Brian K; Wald, Abigail I; Singhi, Aatur D

    2016-09-01

    Within the past few decades, there has been a dramatic increase in the detection of incidental pancreatic cysts. It is reported a pancreatic cyst is identified in up to 2.6% of abdominal scans. Many of these cysts, including serous cystadenomas and pseudocysts, are benign and can be monitored clinically. In contrast, mucinous cysts, which include intraductal papillary mucinous neoplasms and mucinous cystic neoplasms, have the potential to progress to pancreatic adenocarcinoma. In this review, we discuss the current management guidelines for pancreatic cysts, their underlying genetics, and the integration of molecular testing in cyst classification and prognostication. PMID:27523971

  19. Relationship between pancreatic hormones and glucose metabolism: A cross-sectional study in patients after acute pancreatitis.

    PubMed

    Pendharkar, Sayali A; Asrani, Varsha M; Xiao, Amy Y; Yoon, Harry D; Murphy, Rinki; Windsor, John A; Petrov, Maxim S

    2016-07-01

    Abnormal glucose metabolism is present in almost 40% of patients after acute pancreatitis, but its pathophysiology has been poorly investigated. Pancreatic hormone derangements have been sparingly studied to date, and their relationship with abnormal glucose metabolism is largely unknown. The aim was to investigate the associations between pancreatic hormones and glucose metabolism after acute pancreatitis, including the effect of potential confounders. This was a cross-sectional study of 83 adult patients after acute pancreatitis. Fasting venous blood was collected from all patients and used for analysis of insulin, glucagon, pancreatic polypeptide, amylin, somatostatin, C-peptide, glucose, and hemoglobin A1c. Statistical analyses were conducted using the modified Poisson regression, multivariable linear regression, and Spearman's correlation. Age, sex, body mass index, recurrence of acute pancreatitis, duration from first attack, severity, and etiology were adjusted for. Increased insulin was significantly associated with abnormal glucose metabolism after acute pancreatitis, in both unadjusted (P = 0.038) and adjusted (P = 0.001) analyses. Patients with abnormal glucose metabolism also had significantly decreased pancreatic polypeptide (P = 0.001) and increased amylin (P = 0.047) in adjusted analyses. Somatostatin, C-peptide, and glucagon were not changed significantly in both unadjusted and adjusted analyses. Increased insulin resistance and reduced insulin clearance may be important components of hyperinsulinemic compensation in patients after acute pancreatitis. Increased amylin and reduced pancreatic polypeptide fasting levels characterize impaired glucose homeostasis. Clinical studies investigating islet-cell hormonal responses to mixed-nutrient meal testing and euglycemic-hyperinsulinemic clamps are now warranted for further insights into the role of pancreatic hormones in glucose metabolism derangements secondary to pancreatic diseases. PMID:27173509

  20. [Neurological lower torso function test. A new assessment].

    PubMed

    Merkert, J; Butz, S; Nieczaj, R; Steinhagen-Thiessen, E; Eckardt, R

    2013-02-01

    The neurological lower torso function test was developed in addition to the Berg Balance Scale as an assessment for diagnosis and follow-up of lower torso stability and functioning in neurological patients, used for example in subjects in the early rehabilitation phase or still showing low motoric recovery after suffering a stroke. Due to the ground effect for changes in severely affected neurological patients, other tests currently available do not provide an adequate level of sensitivity. The neurological function test was integrated into the study "Combined whole body vibration and balance training using Vibrosphere" with 66 inpatient/partial inpatient neurological subjects ≥ 60 years. Based on six tasks, a qualitative assessment of the selective function of movement and posture tone of the lower extremity, the muscular system around the hip, and the lower torso are performed. Analogous to the Berg Balance Scale, a 5 point scale is used. It shows a high degree of reliability and responsiveness and can be performed with little effort of time and personnel. PMID:22733479

  1. Progress in standardizing and harmonizing thyroid function tests.

    PubMed

    Faix, James D; Miller, W Greg

    2016-09-01

    Iodine is an essential component of thyroid hormone. Because thyroid hormone synthesis is affected by iodine deficiency on the one hand and by excess iodine intake on the other, thyroid function biomarkers may be useful for assessing iodine status and studying the effects of iodine supplementation. However, reference intervals for some of the most useful thyroid function biomarkers, including serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroglobulin, vary widely due to variability in the commercially available immunoassays for these tests. Recognizing the need for standardization of thyroid function testing, the International Federation of Clinical Chemistry and Laboratory Medicine established a working group, later restructured as the Committee for Standardization of Thyroid Function Tests, to examine its feasibility. The committee has established a conventional reference measurement procedure for FT4 and an approach to harmonization of results for TSH. Panels of single-donation human blood specimens that span the measuring interval of the immunoassays were used to assess the performance of commercially available immunoassays and form the basis for their recalibration. Recalibration of the manufacturers' methods for both FT4 and TSH has shown that the variability among immunoassays can be successfully eliminated for euthyroid individuals as well as for patients with thyroid disease. The committee is not investigating the standardization of thyroglobulin at the present time. PMID:27534642

  2. [Exocrine pancreatic insufficiency in dogs].

    PubMed

    van Noort, R

    1990-07-01

    Pancreatic exocrine insufficiency is the most common cause of maldigestion in dogs. This is usually caused by irreversible atrophy of the pancreas which subsequently requires life-long substitution therapy. The pathophysiology, symptoms and diagnosis are briefly reviewed in the present paper. The Trypsin-like-immunoreactivity test is recommended for establishing the diagnosis. Finally, treatment and possible causes of the failure of therapy are discussed. PMID:2196714

  3. Parathyroid hormone-related protein and its receptors: nuclear functions and roles in the renal and cardiovascular systems, the placental trophoblasts and the pancreatic islets

    PubMed Central

    Clemens, Thomas L; Cormier, Sarah; Eichinger, Anne; Endlich, Karlhans; Fiaschi-Taesch, Nathalie; Fischer, Evelyne; Friedman, Peter A; Karaplis, Andrew C; Massfelder, Thierry; Rossert, Jérôme; Schlüter, Klaus-Dieter; Silve, Caroline; Stewart, Andrew F; Takane, Karen; Helwig, Jean-Jacques

    2001-01-01

    The cloning of the so-called ‘parathyroid hormone-related protein' (PTHrP) in 1987 was the result of a long quest for the factor which, by mimicking the actions of PTH in bone and kidney, is responsible for the hypercalcemic paraneoplastic syndrome, humoral calcemia of malignancy. PTHrP is distinct from PTH in a number of ways. First, PTHrP is the product of a separate gene. Second, with the exception of a short N-terminal region, the structure of PTHrP is not closely related to that of PTH. Third, in contrast to PTH, PTHrP is a paracrine factor expressed throughout the body. Finally, most of the functions of PTHrP have nothing in common with those of PTH. PTHrP is a poly-hormone which comprises a family of distinct peptide hormones arising from post-translational endoproteolytic cleavage of the initial PTHrP translation products. Mature N-terminal, mid-region and C-terminal secretory forms of PTHrP are thus generated, each of them having their own physiologic functions and probably their own receptors. The type 1 PTHrP receptor, binding both PTH(1-34) and PTHrP(1-36), is the only cloned receptor so far. PTHrP is a PTH-like calciotropic hormone, a myorelaxant, a growth factor and a developmental regulatory molecule. The present review reports recent aspects of PTHrP pharmacology and physiology, including: (a) the identification of new peptides and receptors of the PTH/PTHrP system; (b) the recently discovered nuclear functions of PTHrP and the role of PTHrP as an intracrine regulator of cell growth and cell death; (c) the physiological and developmental actions of PTHrP in the cardiovascular and the renal glomerulo-vascular systems; (d) the role of PTHrP as a regulator of pancreatic beta cell growth and functions, and, (e) the interactions of PTHrP and calcium-sensing receptors for the control of the growth of placental trophoblasts. These new advances have contributed to a better understanding of the pathophysiological role of PTHrP, and will help to identify

  4. A fully automated, quantitative test of upper limb function.

    PubMed

    Prochazka, Arthur; Kowalczewski, Jan

    2015-01-01

    The Rehabilitation Joystick for Computerized Exercise (ReJoyce, Rehabtronics Inc., Edmonton, Alberta, Canada), is a workstation on which participants exercise dexterous movement tasks in the guise of computer games. The system incorporates the ReJoyce Arm and Hand Function Test (RAHFT). Here the authors evaluate the RAHFT against the Action Research Arm Test (ARAT) and the Fugl-Meyer Assessment (FMA). All 3 tests were performed in 36 separate sessions in 13 tetraplegic individuals. Concurrent and criterion validities of the RAHFT were supported by a high level of correlation with the ARAT (r2 = .88). Regarding responsiveness, the effect size of the RAHFT at week 6 of 1 hr/day exercise training was 1.8. Regarding reliability, the mean test-retest difference in RAHFT baseline scores was 0.67% ± 3.6%, which was not statistically significant. The RAHFT showed less ceiling effect than either ARAT or FMA. These data help validate the RAHFT as a quantitative, automated alternative to the ARAT and FMA. The RAHFT is the first comprehensive test of arm and dexterous hand function that does not depend on human judgment. It offers a standardized, quantitative outcome evaluation, which can be performed not only in the clinic, but also in the participant's home, administered by a remote therapist over the Internet. PMID:25575220

  5. Validation of Cardiovascular Parameters During NASA's Functional Task Test

    NASA Technical Reports Server (NTRS)

    Arzeno, N. M.; Stenger, M. B.; Bloomberg, J. J.; Platts, Steven H.

    2008-01-01

    Microgravity-induced physiological changes, including cardiovascular deconditioning may impair crewmembers f capabilities during exploration missions on the Moon and Mars. The Functional Task Test (FTT), which will be used to assess task performance in short and long duration astronauts, consists of 7 functional tests to evaluate crewmembers f ability to perform activities to be conducted in a partial-gravity environment or following an emergency landing on Earth. The Recovery from Fall/Stand Test (RFST) tests both the subject fs ability to get up from a prone position and orthostatic intolerance. PURPOSE: Crewmembers have never become presyncopal in the first 3 min of quiet stand, yet it is unknown whether 3 min is long enough to cause similar heart rate fluctuations to a 5-min stand. The purpose of this study was to validate and test the reliability of heart rate variability (HRV) analysis of a 3-min quiet stand. METHODS: To determine the validity of using 3 vs. 5-min of standing to assess HRV, 7 healthy subjects remained in a prone position for 2 min, stood up quickly and stood quietly for 6 min. ECG and continuous blood pressure data were recorded. Mean R-R interval and spectral HRV were measured in minutes 0-3 and 0-5 following the heart rate transient due to standing. Significant differences between the segments were determined by a paired t-test. To determine the reliability of the 3-min stand test, 13 healthy subjects completed 3 trials of the complete FTT on separate days, including the RFST with a 3-min stand test. Analysis of variance (ANOVA) was performed on the HRV measures. RESULTS: Spectral HRV measures reflecting autonomic activity were not different (p>0.05) during the 0-3 and 0-5 min segment (mean R-R interval: 738+/-74 ms, 728+/-69 ms; low frequency to high frequency ratio: 6.5+/-2.2, 7.7+/-2.7; normalized high frequency: 0.19+/-0.03, 0.18+/-0.04). The average coefficient of variation for mean R-R interval, systolic and diastolic blood pressures

  6. Polyphenol-Rich Extract of Syzygium cumini Leaf Dually Improves Peripheral Insulin Sensitivity and Pancreatic Islet Function in Monosodium L-Glutamate-Induced Obese Rats.

    PubMed

    Sanches, Jonas R; França, Lucas M; Chagas, Vinicyus T; Gaspar, Renato S; Dos Santos, Kayque A; Gonçalves, Luciana M; Sloboda, Deborah M; Holloway, Alison C; Dutra, Richard P; Carneiro, Everardo M; Cappelli, Ana Paula G; Paes, Antonio Marcus de A

    2016-01-01

    Syzygium cumini (L.) Skeels (Myrtaceae) has been traditionally used to treat a number of illnesses. Ethnopharmacological studies have particularly addressed antidiabetic and metabolic-related effects of extracts prepared from its different parts, especially seed, and pulp-fruit, however. there is a lack of studies on phytochemical profile and biological properties of its leaf. As there is considerable interest in bioactive compounds to treat metabolic syndrome and its clustered risk factors, we sought to characterize the metabolic effects of hydroethanolic extract of S. cumini leaf (HESc) on lean and monosodium L-glutamate (MSG)-induced obese rats. HPLC-MS/MS characterization of the HESc polyphenolic profile, at 254 nm, identified 15 compounds pertaining to hydrolysable tannin and flavanol subclasses. At 60 days of age, both groups were randomly assigned to receive HESc (500 mg/kg) or vehicle for 30 days. At the end of treatment, obese+HESc exhibited significantly lower body weight gain, body mass index, and white adipose tissue mass, compared to obese rats receiving vehicle. Obese rats treated with HESc showed a twofold increase in lipolytic activity in the periepididymal fat pad, as well as, brought triglyceride levels in serum, liver and skeletal muscle back to levels close those found in lean animals. Furthermore, HESc also improved hyperinsulinemia and insulin resistance in obese+HESc rats, which resulted in partial reversal of glucose intolerance, as compared to obese rats. HESc had no effect in lean rats. Assessment of ex vivo glucose-stimulated insulin secretion showed HESc potentiated pancreatic function in islets isolated from both lean and obese rats treated with HESc. In addition, HESc (10-1000 μg/mL) increased glucose stimulated insulin secretion from both isolated rat islets and INS-1E β-cells. These data demonstrate that S. cumini leaf improved peripheral insulin sensitivity via stimulating/modulating β-cell insulin release, which was associated

  7. Hexarelin Protects Rodent Pancreatic Β-Cells Function from Cytotoxic Effects of Streptozotocin Involving Mitochondrial Signalling Pathways In Vivo and In Vitro

    PubMed Central

    Chen, Jiezhong; Lin, Chao; Shao, Renfu; Yan, Chunxia; Chen, Chen

    2016-01-01

    Mitochondrial functions are crucial for pancreatic β-cell survival and glucose-induced insulin secretion. Hexarelin (Hex) is a synthetic small peptide ghrelin analogue, which has been shown to protect cardiomyocytes from the ischemia-reperfusion process. In this study, we used in vitro and in vivo models of streptozotocin (STZ)-induced β-cell damage to study the protective effect of Hex and the associated mechanisms. We found that STZ produced a cytotoxic effect in a dose- and time-dependent manner in MIN6 cells (a mouse β-cell line). Hex (1.0 μM) decreased the STZ-induced damage in β-cells. Rhodamine 123 assay and superoxide DHE production assay revealed that Hex ameliorated STZ-induced mitochondrial damage and excessive superoxide activity in β-cells. In addition, Hex significantly reduced STZ-induced expression of cleaved Caspases-3, Caspases-9 and the ratio of pro-apoptotic protein Bax to anti-apoptotic protein Bcl-2 in MIN6 cells. We further examined the in vivo effect of Hex in a rat model of type 1 diabetes induced by STZ injection. Hex ameliorated STZ-induced decrease in plasma insulin and protected the structure of islets from STZ-induced disruption. Hex also ameliorated STZ-induced expression of cleaved Caspase-9 and the Bax in β-cells. In conclusion, our data indicate that Hex is able to protects β-cell mass from STZ-caused cytotoxic effects involving mitochondrial pathways in vitro and in vivo. Hex may serve as a potential protective agent for the management of diabetes. PMID:26918825

  8. Polyphenol-Rich Extract of Syzygium cumini Leaf Dually Improves Peripheral Insulin Sensitivity and Pancreatic Islet Function in Monosodium L-Glutamate-Induced Obese Rats

    PubMed Central

    Sanches, Jonas R.; França, Lucas M.; Chagas, Vinicyus T.; Gaspar, Renato S.; dos Santos, Kayque A.; Gonçalves, Luciana M.; Sloboda, Deborah M.; Holloway, Alison C.; Dutra, Richard P.; Carneiro, Everardo M.; Cappelli, Ana Paula G.; Paes, Antonio Marcus de A.

    2016-01-01

    Syzygium cumini (L.) Skeels (Myrtaceae) has been traditionally used to treat a number of illnesses. Ethnopharmacological studies have particularly addressed antidiabetic and metabolic-related effects of extracts prepared from its different parts, especially seed, and pulp-fruit, however. there is a lack of studies on phytochemical profile and biological properties of its leaf. As there is considerable interest in bioactive compounds to treat metabolic syndrome and its clustered risk factors, we sought to characterize the metabolic effects of hydroethanolic extract of S. cumini leaf (HESc) on lean and monosodium L-glutamate (MSG)-induced obese rats. HPLC-MS/MS characterization of the HESc polyphenolic profile, at 254 nm, identified 15 compounds pertaining to hydrolysable tannin and flavanol subclasses. At 60 days of age, both groups were randomly assigned to receive HESc (500 mg/kg) or vehicle for 30 days. At the end of treatment, obese+HESc exhibited significantly lower body weight gain, body mass index, and white adipose tissue mass, compared to obese rats receiving vehicle. Obese rats treated with HESc showed a twofold increase in lipolytic activity in the periepididymal fat pad, as well as, brought triglyceride levels in serum, liver and skeletal muscle back to levels close those found in lean animals. Furthermore, HESc also improved hyperinsulinemia and insulin resistance in obese+HESc rats, which resulted in partial reversal of glucose intolerance, as compared to obese rats. HESc had no effect in lean rats. Assessment of ex vivo glucose-stimulated insulin secretion showed HESc potentiated pancreatic function in islets isolated from both lean and obese rats treated with HESc. In addition, HESc (10–1000 μg/mL) increased glucose stimulated insulin secretion from both isolated rat islets and INS-1E β-cells. These data demonstrate that S. cumini leaf improved peripheral insulin sensitivity via stimulating/modulating β-cell insulin release, which was associated

  9. [Problems in the determination of pancreatic enzymes for the quantitative functional diagnosis of the pancreas in children].

    PubMed

    Senger, H; Beyreiss, K; Scheerschmidt, G; Dettmer, D; Müller, F

    1981-01-01

    Pancreozymin-secretin tests were carried out in children aged from 0,5 till 12 years by means of a two lumen tube of the Salem-Sump-type and a three lumen perfusion tube. For stimulation we used 2 U/kg of the hormones, each from BOOTs-Corp. Amylase was determined with dinitrosalicylic acid, lipase by titration of acidic equivalents after half hour incubation and trypsin and chymotrypsin with TAME and BTEE respectively. We used PEG 4000 as marker and quantified enzymes secretion as well as liquid secretion by it. We got up to 50% lower results by testing with the two lumen tube. If we are laying the perfusion tube we measured an elevation of the two lumen tube. If we are laying the perfusion tube we measured an elevation of the II-hydroxycorticoides. The concentration of the enzymes in the specimines before perfusion on 3 consecutive days fell by 90% on the average. We discussed some problems of the determination of enzymes and performing of the tests by means of the results. PMID:6165543

  10. Clinical efficacy of serum lipase subtype analysis for the differential diagnosis of pancreatic and non-pancreatic lipase elevation

    PubMed Central

    Bang, Chang Seok; Kim, Jin Bong; Park, Sang Hyun; Baik, Gwang Ho; Su, Ki Tae; Yoon, Jai Hoon; Kim, Yeon Soo; Kim, Dong Joon

    2016-01-01

    Background/Aims: Non-pancreatic elevations of serum lipase have been reported, and differential diagnosis is necessary for clinical practice. This study aimed to evaluate the clinical efficacy of serum lipase subtype analysis for the differential diagnosis of pancreatic and non-pancreatic lipase elevation. Methods: Patients who were referred for the serum lipase elevation were prospectively enrolled. Clinical findings and serum lipase subtypes were analyzed and compared by dividing the patients into pancreatitis and non-pancreatitis groups. Results: A total of 34 patients (12 pancreatitis vs. 22 non-pancreatitis cases) were enrolled. In univariate analysis, the fraction of pancreatic lipase (FPL) in the total amount of serum lipase subtypes was statistically higher in patients with pancreatitis ([median, 0.004; interquartile range [IQR], 0.003 to 0.011] vs. [median, 0.002; IQR, 0.001 to 0.004], p = 0.04). Based on receiver operating characteristic curve analysis for the prediction of acute pancreatitis, FPL was the most valuable predictor (area under the receiver-operating characteristic curve [AUROC], 0.72; 95% confidence interval [CI], 0.54 to 0.86; sensitivity, 83.3%; specificity, 63.6%; positive predictive value, 55.6%; negative predictive value, 97.5%). In multivariate analysis, a cut-off value higher than 0.0027 for the FPL was associated with acute pancreatitis (odds ratio, 8.3; 95% CI, 1.3 to 51.7; p = 0.02). Conclusions: The results did not support that serum lipase subtype analysis could replace standard lipase measurement for the diagnosis of acute pancreatitis. However, the test demonstrated adequate sensitivity for use in triage or as an add-on test for serum lipase elevation. PMID:27243230

  11. Pancreatic Bicarbonate Secretion Involves Two Proton Pumps*

    PubMed Central

    Novak, Ivana; Wang, Jing; Henriksen, Katrine L.; Haanes, Kristian A.; Krabbe, Simon; Nitschke, Roland; Hede, Susanne E.

    2011-01-01

    Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium express H+/HCO3− transporters, which depend on gradients created by the Na+/K+-ATPase. However, the model cannot fully account for high-bicarbonate concentrations, and other active transporters, i.e. pumps, have not been explored. Here we show that pancreatic ducts express functional gastric and non-gastric H+-K+-ATPases. We measured intracellular pH and secretion in small ducts isolated from rat pancreas and showed their sensitivity to H+-K+ pump inhibitors and ion substitutions. Gastric and non-gastric H+-K+ pumps were demonstrated on RNA and protein levels, and pumps were localized to the plasma membranes of pancreatic ducts. Quantitative analysis of H+/HCO3− and fluid transport shows that the H+-K+ pumps can contribute to pancreatic secretion in several species. Our results call for revision of the bicarbonate transport physiology in pancreas, and most likely other epithelia. Furthermore, because pancreatic ducts play a central role in several pancreatic diseases, it is of high relevance to understand the role of H+-K+ pumps in pathophysiology. PMID:20978133

  12. Treatment of Pancreatic Cancer with Pharmacological Ascorbate

    PubMed Central

    Cieslak, John A.; Cullen, Joseph J.

    2016-01-01

    The prognosis for patients diagnosed with pancreatic cancer remains dismal, with less than 3% survival at 5 years. Recent studies have demonstrated that high-dose, intravenous pharmacological ascorbate (ascorbic acid, vitamin C) induces cytotoxicity and oxidative stress selectively in pancreatic cancer cells vs. normal cells, suggesting a promising new role of ascorbate as a therapeutic agent. At physiologic concentrations, ascorbate functions as a reducing agent and antioxidant. However, when pharmacological ascorbate is given intravenously, it is possible to achieve millimolar plasma concentration. At these pharmacological levels, and in the presence of catalytic metal ions, ascorbate can induce oxidative stress through the generation of hydrogen peroxide (H2O2). Recent in vitro and in vivo studies have demonstrated ascorbate oxidation occurs extracellularly, generating H2O2 flux into cells resulting in oxidative stress. Pharmacologic ascorbate also inhibits the growth of pancreatic tumor xenografts and displays synergistic cytotoxic effects when combined with gemcitabine in pancreatic cancer. Phase I trials of pharmacological ascorbate in pancreatic cancer patients have demonstrated safety and potential efficacy. In this chapter, we will review the mechanism of ascorbate-induced cytotoxicity, examine the use of pharmacological ascorbate in treatment and assess the current data supporting its potential as an adjuvant in pancreatic cancer. PMID:26201606

  13. Epithelial dynamics of pancreatic branching morphogenesis

    PubMed Central

    Villasenor, Alethia; Chong, Diana C.; Henkemeyer, Mark; Cleaver, Ondine

    2010-01-01

    The mammalian pancreas is a highly branched gland, essential for both digestion and glucose homeostasis. Pancreatic branching, however, is poorly understood, both at the ultrastructural and cellular levels. In this article, we characterize the morphogenesis of pancreatic branches, from gross anatomy to the dynamics of their epithelial organization. We identify trends in pancreatic branch morphology and introduce a novel mechanism for branch formation, which involves transient epithelial stratification and partial loss of cell polarity, changes in cell shape and cell rearrangements, de novo tubulogenesis and epithelial tubule remodeling. In contrast to the classical epithelial budding and tube extension observed in other organs, a pancreatic branch takes shape as a multi-lumen tubular plexus coordinately extends and remodels into a ramifying, single-lumen ductal system. Moreover, our studies identify a role for EphB signaling in epithelial remodeling during pancreatic branching. Overall, these results illustrate distinct, step-wise cellular mechanisms by which pancreatic epithelium shapes itself to create a functional branching organ. PMID:21098570

  14. Knowledge Gaps in Rodent Pancreas Biology: Taking Human Pluripotent Stem Cell-Derived Pancreatic Beta Cells into Our Own Hands

    PubMed Central

    Santosa, Munirah Mohamad; Low, Blaise Su Jun; Pek, Nicole Min Qian; Teo, Adrian Kee Keong

    2016-01-01

    In the field of stem cell biology and diabetes, we and others seek to derive mature and functional human pancreatic β cells for disease modeling and cell replacement therapy. Traditionally, knowledge gathered from rodents is extended to human pancreas developmental biology research involving human pluripotent stem cells (hPSCs). While much has been learnt from rodent pancreas biology in the early steps toward Pdx1+ pancreatic progenitors, much less is known about the transition toward Ngn3+ pancreatic endocrine progenitors. Essentially, the later steps of pancreatic β cell development and maturation remain elusive to date. As a result, the most recent advances in the stem cell and diabetes field have relied upon combinatorial testing of numerous growth factors and chemical compounds in an arbitrary trial-and-error fashion to derive mature and functional human pancreatic β cells from hPSCs. Although this hit-or-miss approach appears to have made some headway in maturing human pancreatic β cells in vitro, its underlying biology is vaguely understood. Therefore, in this mini-review, we discuss some of these late-stage signaling pathways that are involved in human pancreatic β cell differentiation and highlight our current understanding of their relevance in rodent pancreas biology. Our efforts here unravel several novel signaling pathways that can be further studied to shed light on unexplored aspects of rodent pancreas biology. New investigations into these signaling pathways are expected to advance our knowledge in human pancreas developmental biology and to aid in the translation of stem cell biology in the context of diabetes treatments. PMID:26834702

  15. Improving the Outcome of Acute Pancreatitis.

    PubMed

    Bruno, Marco J

    2016-01-01

    Acute pancreatitis (AP) is the most common indication for hospital admission and its incidence is rising. It has a variable prognosis, which is mainly dependent upon the development of persistent organ failure and infected necrotizing pancreatitis. In the past few years, based on large-scale multicenter randomized trials, some novel insights regarding clinical management have emerged. In patients with infected pancreatic necrosis, a step-up approach of percutaneous catheter drainage followed by necrosectomy only when the patient does not improve, reduces new-onset organ failure and prevents the need for necrosectomy in about a third of patients. A randomized pilot study comparing surgical to endoscopic necrosectomy in patients with infected necrotizing pancreatitis showed a striking reduction of the pro-inflammatory response following endoscopic necrosectomy. These promising results have recently been tested in a large multicenter randomized trial whose results are eagerly awaited. Contrary to earlier data from uncontrolled studies, a large multicenter randomized trial comparing early (within 24 h) nasoenteric tube feeding compared with an oral diet after 72 h, did not show that early nasoenteric tube feeding was superior in reducing the rate of infection or death in patients with AP at high risk for complications. Although early ERCP does not have a role in the treatment of predicted mild pancreatitis, except in the case of concomitant cholangitis, it may ameliorate the disease course in patients with predicted severe pancreatitis. Currently, a large-scale randomized study is underway and results are expected in 2017. PMID:27336312

  16. CFTR: A New Horizon in the Pathomechanism and Treatment of Pancreatitis.

    PubMed

    Hegyi, Péter; Wilschanski, Michael; Muallem, Shmuel; Lukacs, Gergely L; Sahin-Tóth, Miklós; Uc, Aliye; Gray, Michael A; Rakonczay, Zoltán; Maléth, József

    2016-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel that conducts chloride and bicarbonate ions across epithelial cell membranes. Mutations in the CFTR gene diminish the ion channel function and lead to impaired epithelial fluid transport in multiple organs such as the lung and the pancreas resulting in cystic fibrosis. Heterozygous carriers of CFTR mutations do not develop cystic fibrosis but exhibit increased risk for pancreatitis and associated pancreatic damage characterized by elevated mucus levels, fibrosis, and cyst formation. Importantly, recent studies demonstrated that pancreatitis causing insults, such as alcohol, smoking, or bile acids, strongly inhibit CFTR function. Furthermore, human studies showed reduced levels of CFTR expression and function in all forms of pancreatitis. These findings indicate that impairment of CFTR is critical in the development of pancreatitis; therefore, correcting CFTR function could be the first specific therapy in pancreatitis. In this review, we summarize recent advances in the field and discuss new possibilities for the treatment of pancreatitis. PMID:26856995

  17. Pheochromocytoma with Markedly Abnormal Liver Function Tests and Severe Leukocytosis

    PubMed Central

    Eun, Chai Ryoung; Ahn, Jae Hee; Seo, Ji A

    2014-01-01

    Pheochromocytoma is a rare neuroendocrine tumor arising from the medulla of the adrenal glands, which causes an overproduction of catecholamines. The common symptoms are headache, palpitations, and sweating; however, various other clinical manifestations might also be present. Accurate diagnosis of pheochromocytoma is important because surgical treatment is usually successful, and associated clinical problems are reversible if treated early. A 49-year-old man with a history of uncontrolled hypertension and diabetes mellitus presented with chest pain, fever, and sweating. His liver function tests and white blood cell counts were markedly increased and his echocardiography results suggested stress-induced cardiomyopathy. His abdominal computed tomography showed a 5×5-cm-sized tumor in the left adrenal gland, and laboratory tests confirmed catecholamine overproduction. After surgical resection of the left adrenal gland, his liver function tests and white blood cell counts normalized, and echocardiography showed normal cardiac function. Moreover, his previous antihypertensive regimen was deescalated, and his previously uncontrolled blood glucose levels normalized without medication. PMID:24741459

  18. Beta-carotene blood test

    MedlinePlus

    ... inflammation ( pancreatitis ) or the organ not producing enough enzymes (pancreatic insufficiency) Small intestine disorder called celiac disease This test plays a valuable role in diagnosing vitamin A deficiency. But the test ...

  19. Test experience effects in longitudinal comparisons of adult cognitive functioning.

    PubMed

    Salthouse, Timothy

    2015-09-01

    It is widely recognized that experience with cognitive tests can influence estimates of cognitive change. Prior research has estimated experience effects at the level of groups by comparing the performance of a group of participants tested for the second time with the performance of a different group of participants at the same age tested for the first time. This twice-minus-once-tested method was adapted in the current study to derive estimates of test experience at the level of individual participants. Among the major findings were that experience estimates were smaller at older ages, with measures of vocabulary and speed compared to measures of memory, reasoning, and spatial visualization, and with longer intervals between the first and second occasion. Although relations of overall cognitive ability with test experience effects were weak, there were significant correlations among the experience estimates in different cognitive domains. These results imply that at least in adulthood, simple measures of cognitive change likely underestimate maturational influences on cognitive functioning, and to a greater extent in young adults than in older adults. PMID:26098579

  20. Pulmonary function tests in children with beta-thalassemia major.

    PubMed

    Abu-Ekteish, F M; Al-Rimawi, H S; Al-Ali, M K; Shehabi, I M

    2007-01-01

    Lung function abnormality is a known complication of thalassemia, but the results of studies in pulmonary function have been inconsistent. This study was conducted to describe the type of lung impairment in thalassemic children. Pulmonary function tests were conducted in 40 children with beta-thalassemia major, 23 males and 17 females. Tests included spirometry, total lung capacity (TLC), single breath diffusing capacity of the lung for carbon monoxide (DL(CO)) and arterial blood gases. Serum ferritin level was measured in all children to study its relationship to lung function impairment. A predominantly restrictive pattern was seen in 14 patients (35%). These patients had a significant reduction in RV, FVC, TLC and PEF with an FEV1/FVC ratio of more than 75%. Obstructive airway disease was found in six patients (15%), with an FEV1/FVC ratio less than 75%, increased RV and reduced FEF(25%-75%). Impairment of diffusion was found in 10 patients (25%), with DL(CO) reduced to less than 80% of the predicted value. Arterial blood gases results showed that no patient was hypoxic. No correlation was found between the severity of restrictive or obstructive disease and the serum ferritin level. There was a significant linear correlation between age and serum ferritin level (P < 0.019). Patients with thalassemia have a predominantly restrictive lung dysfunction pattern. This may be due to pulmonary parenchymal pathology, although the reason for the obstructive pattern seen in a small proportion of patients remains obscure. PMID:17416149

  1. Sensitivity and specificity of the functional hallux limitus test to predict foot function.

    PubMed

    Payne, Craig; Chuter, Vivienne; Miller, Kathryn

    2002-05-01

    Functional hallux limitus is an underrecognized entity that generally does not produce symptoms but can result in a variety of compensatory mechanisms that can produce symptoms. Clinically, hallux limitus can be determined by assessing the range of motion available at the first metatarsophalangeal joint while the first ray is prevented from plantarflexing. The aim of this study was to determine the sensitivity and specificity of this clinical test to predict abnormal excessive midtarsal joint function during gait. A total of 86 feet were examined for functional hallux limitus and abnormal pronation of the midtarsal joint during late midstance. The test had a sensitivity of 0.72 and a specificity of 0.66, suggesting that clinicians should consider functional hallux limitus when there is late midstance pronation of the midtarsal joint during gait. PMID:12015407

  2. The effect of rosuvastatin on insulin sensitivity and pancreatic beta-cell function in nondiabetic renal transplant recipients.

    PubMed

    Sharif, A; Ravindran, V; Moore, R; Dunseath, G; Luzio, S; Owens, D; Baboolal, K

    2009-06-01

    Interventions to attenuate abnormal glycemia posttransplantation are required. In addition, surrogate markers of declining glycemic control are valuable. Statins may have pleiotropic properties that attenuate abnormal glucose metabolism. We hypothesized statins would improve glucose metabolism and HbA1c would be advantageous as a surrogate for worsening glycemia. We conducted a prospective, randomized, placebo controlled, crossover study in 20 nondiabetic renal transplant recipients at low risk for NODAT and compared effects of rosuvastatin on insulin secretion/sensitivity. Mathematical model analysis of an intravenous glucose tolerance test determined first-phase insulin secretion, insulin sensitivity and disposition index. Second-phase insulin secretion was determined with a meal tolerance test. Biochemical/clinical parameters were also assessed. Rosuvastatin significantly improved total cholesterol (-30%, p < 0.001), LDL cholesterol (-44%, p < 0.001) and triglycerides (-19%, p = 0.013). C-reactive protein decreased but failed to achieve statistical significance (-31%, p = 0.097). Rosuvastatin failed to influence any glycemic physiological parameter, although an inadequate timeframe to allow pleiotropic mechanisms to clinically manifest raises the possibility of a type II statistical error. On multivariate analysis, glycated hemoglobin (HbA1c) correlated with disposition index (R(2)= 0.201, p = 0.006), first-phase insulin secretion (R(2)= 0.106, p = 0.049) and insulin sensitivity (R(2)= 0.136, p = 0.029). Rosuvastatin fails to modify glucose metabolism in low-risk patients posttransplantation but HbA1c is a useful surrogate for declining glycemic control. PMID:19459810

  3. Functional testing of hepatocytes following their recovery from cryopreservation.

    PubMed

    Innes, G K; Fuller, B J; Hobbs, K E

    1988-02-01

    Various tests of function have been suggested for assessing hepatocytes recovered from cryopreservation. In this study we have investigated hepatocyte attachment during tissue culture and cellular density in order to assess function and compared them with two classical dye exposure tests. The ability of hepatocytes to exclude trypan blue dye (TB) and metabolize fluorescein diacetate (FDA) was demonstrated. In populations of freshly prepared hepatocytes 88.07% were able to exclude TB and 87.31% were able to metabolize FDA. However in populations of hepatocytes recovered after cryopreservation using 1.5 M dimethyl sulfoxide as cryoprotectant only 33.44% were able to exclude TB and 31.59% able to metabolize FDA. Both of these tests gave the same estimate of functional ability. Density gradient centrifugation of hepatocytes on Percoll 400 (Pharmacia, Uppsala, Sweden) separated two populations of hepatocytes; one (density ca.1.07 g/ml Percoll) in which most of the cells were able to exclude TB and the second (density ca. 1.02 g/ml Percoll) in which they were stained blue. The dense population was highly enriched in dye-excluding hepatocytes: freshly prepared hepatocytes, 92.4%, and cryopreserved hepatocytes, 88.66%. When samples of these cells (2 x 10(6) dye-excluding cells per dish) were tested for their ability to attach to tissue culture dishes only 17.28% of the cryopreserved hepatocytes were able to attach compared to 55.28% of the freshly prepared cells. We conclude that cryopreservation of hepatocytes produces a population of cells which are not metabolically identical to a population of freshly prepared hepatocytes even though they appear to have the same buoyant density and dye-excluding capabilities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3349809

  4. Conduct disorder and cognitive functioning: testing three causal hypotheses.

    PubMed

    Schonfeld, I S; Shaffer, D; O'Connor, P; Portnoy, S

    1988-08-01

    The sample consisted of black adolescents who were members of the Columbia-Presbyterian chapter of the Collaborative Perinatal Project from birth to age 7. At age 17, subjects and their parents were administered a battery of instruments that included standardized psychiatric diagnostic interviews as part of a call-back study. Results from least-squares and logistic regression analyses were compatible with the hypothesis that deficiencies in cognitive functioning are causally related to adolescent conduct disorder as defined by DSM III. The results suggested that the relation of cognitive functioning to psychiatric status appears to be specific to conduct disorders. The results were incompatible with a "third" variable hypothesis (third factors included neurological status and environmental disadvantage) and the hypothesis that conduct problems lead to deficits in cognitive functioning. The 3 most (and equally) important factors in accounting for age-17 conduct disorder were cognitive functioning, parent psychopathology, and early aggression. A closer look at the data tentatively suggested that a broad deficiency in acculturational learning, rather than narrowly focused social cognitive differences or native endowment, constitutes a key element in the link between cognitive functioning and conduct disorder. Test bias was ruled out as a possible explanation for the results. PMID:3168633

  5. APC promoter is frequently methylated in pancreatic juice of patients with pancreatic carcinomas or periampullary tumors

    PubMed Central

    Ginesta, Mireia M.; Diaz-Riascos, Zamira Vanessa; Busquets, Juli; Pelaez, Núria; Serrano, Teresa; Peinado, Miquel Àngel; Jorba, Rosa; García-Borobia, Francisco Javier; Capella, Gabriel; Fabregat, Joan

    2016-01-01

    Early detection of pancreatic and periampullary neoplasms is critical to improve their clinical outcome. The present authors previously demonstrated that DNA hypermethylation of adenomatous polyposis coli (APC), histamine receptor H2 (HRH2), cadherin 13 (CDH13), secreted protein acidic and cysteine rich (SPARC) and engrailed-1 (EN-1) promoters is frequently detected in pancreatic tumor cells. The aim of the present study was to assess their prevalence in pancreatic juice of carcinomas of the pancreas and periampullary area. A total of 135 pancreatic juices obtained from 85 pancreatic cancer (PC), 26 ampullary carcinoma (AC), 10 intraductal papillary mucinous neoplasm (IPMN) and 14 chronic pancreatitis (CP) patients were analyzed. The methylation status of the APC, HRH2, CDH13, SPARC and EN-1 promoters was analyzed using methylation specific-melting curve analysis (MS-MCA). Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were also tested with allele-specific quantitative polymerase chain reaction amplification. Out of the 5 promoters analyzed, APC (71%) and HRH2 (65%) were the most frequently methylated in PC juice. APC methylation was also detected at a high frequency in AC (76%) and IPMN (80%), but only occasionally observed in CP (7%). APC methylation had a high sensitivity (71–80%) for all types of cancer analyzed. The panel (where a sample scored as positive when ≥2 markers were methylated) did not outperform APC as a single marker. Finally, KRAS detection in pancreatic juice offered a lower sensitivity (50%) and specificity (71%) for detection of any cancer. APC hypermethylation in pancreatic juice, as assessed by MS-MCA, is a frequent event of potential clinical usefulness in the diagnosis of pancreatic and periampullary neoplasms. PMID:27602165

  6. Hyperamylasaemia: pathognomonic to pancreatitis?

    PubMed

    Burden, Sam; Poon, Anna Sau Kuk; Masood, Kausar; Didi, Mohamed

    2013-01-01

    An 82-year-old woman, presented with a history of vomiting, abdominal mass and a significantly raised amylase, but no clinical evidence of pancreatitis. Abdominal ultrasound and CT scans showed an ovarian tumour, and no evidence of pancreatitis-as is often associated with a raised amylase. The patient underwent bilateral ovariectomy and hysterectomy and made a good recovery. PMID:24132440

  7. Pancreatic Cancer Database

    PubMed Central

    Thomas, Joji Kurian; Kim, Min-Sik; Balakrishnan, Lavanya; Nanjappa, Vishalakshi; Raju, Rajesh; Marimuthu, Arivusudar; Radhakrishnan, Aneesha; Muthusamy, Babylakshmi; Khan, Aafaque Ahmad; Sakamuri, Sruthi; Tankala, Shantal Gupta; Singal, Mukul; Nair, Bipin; Sirdeshmukh, Ravi; Chatterjee, Aditi; Prasad, T S Keshava; Maitra, Anirban; Gowda, Harsha; Hruban, Ralph H; Pandey, Akhilesh

    2014-01-01

    Pancreatic cancer is the fourth leading cause of cancer-related death in the world. The etiology of pancreatic cancer is heterogeneous with a wide range of alterations that have already been reported at the level of the genome, transcriptome, and proteome. The past decade has witnessed a large number of experimental studies using high-throughput technology platforms to identify genes whose expression at the transcript or protein levels is altered in pancreatic cancer. Based on expression studies, a number of molecules have also been proposed as potential biomarkers for diagnosis and prognosis of this deadly cancer. Currently, there are no repositories which provide an integrative view of multiple Omics data sets from published research on pancreatic cancer. Here, we describe the development of a web-based resource, Pancreatic Cancer Database (http://www.pancreaticcancerdatabase.org), as a unified platform for pancreatic cancer research. PCD contains manually curated information pertaining to quantitative alterations in miRNA, mRNA, and proteins obtained from small-scale as well as high-throughput studies of pancreatic cancer tissues and cell lines. We believe that PCD will serve as an integrative platform for scientific community involved in pancreatic cancer research. PMID:24839966

  8. Pancreatic adenocarcinoma: Outstanding problems

    PubMed Central

    Zakharova, Olga P; Karmazanovsky, Grigory G; Egorov, Viacheslav I

    2012-01-01

    Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive malignant tumors with an overall 5-year survival rate of less than 4%. Surgical resection remains the only potentially curative treatment but is only possible for 15%-20% of patients with pancreatic adenocarcinoma. About 40% of patients have locally advanced nonresectable disease. In the past, determination of pancreatic cancer resectability was made at surgical exploration. The development of modern imaging techniques has allowed preoperative staging of patients. Institutions disagree about the criteria used to classify patients. Vascular invasion in pancreatic cancers plays a very important role in determining treatment and prognosis. There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer and a unified definition of borderline resectable pancreatic cancer is also lacking. Thus, there is much room for improvement in all aspects of treatment for pancreatic cancer. Multi-detector computed tomography has been widely accepted as the imaging technique of choice for diagnosing and staging pancreatic cancer. With improved surgical techniques and advanced perioperative management, vascular resection and reconstruction are performed more frequently; patients thought once to be unresectable are undergoing radical surgery. However, when attempting heroic surgery, a realistic approach concerning the patient’s age and health status, probability of recovery after surgery, perioperative morbidity and mortality and life quality after tumor resection is necessary. PMID:22655124

  9. VEGF-conjugated alginate hydrogel prompt angiogenesis and improve pancreatic islet engraftment and function in type 1 diabetes.

    PubMed

    Yin, Nina; Han, Yongming; Xu, Hanlin; Gao, Yisen; Yi, Tao; Yao, Jiale; Dong, Li; Cheng, Dejun; Chen, Zebin

    2016-02-01

    Type 1 diabetes was a life-long disease that affected numerous people around the world. Insulin therapy has its limitations that may involve hyperglycemia and heavy burden of patient by repeated dose. Islet transplantation emerged as a promising approach to reach periodical reverse of diabetes, however, transplanted islets suffer from foreign body reaction and lack of nutrition and oxygen supply, especially in the blood-vessel-shortage subcutaneous site which was preferred by patient and surgeon. In this study, we designed and synthesized a vascular endothelial growth factor (VEGF) conjugated alginate material to encapsulate the transplanted islets via 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) reaction, and successful conjugation was confirmed by Nuclear Magnetic Resonance H1 spectrum. The best VEGF concentration (100ng/ml) was determined by the combined studies of the mechanical property and endothelial cell growth assay. In vivo study, conjugated VEGF on alginate exhibited sustained promoting angiogenesis property after subcutaneous transplantation by histology study and islets encapsulated in this material achieved long term therapeutic effect (up to 50days) in the diabetic mice model. In conclusion, this study establishes a simple biomaterial strategy for islet transplantation to enhance islet survival and function, which could be a feasible therapeutic alternative for type 1 diabetes. PMID:26652453

  10. Diagnosis and management of chronic pancreatitis: current knowledge.

    PubMed

    Ammann, Rudolf W

    2006-03-18

    This paper reviews the current literature on chronic pancreatitis (CP). Despite marked progress in diagnostic tools, predominately imaging methods, no consensus has been reached on the nomenclature of CP, ie diagnosis, classification, staging, pathomechanisms of pain and its optimal treatment. A major problem is that no single reliable diagnostic test exists for early-stage CP except histopathology (rarely available). This stage is characterised typically by recurrent acute pancreatitis +/- necrosis (eg pseudocysts). Acute pancreatitis is a well-defined condition caused in 80% of cases by gallstones or alcohol abuse. Alcoholic pancreatitis, in contrast to biliary pancreatitis, progresses to CP in the majority of patients. However, a definite CP-diagnosis is often delayed because progressive dysfunction and/or calcification, the clinical markers of CP, develop on average 5 years from disease onset. The progression rate is variable and depends on several factors eg aetiology, smoking, continued alcohol abuse. Repeated function testing eg by the faecal elastase test, is the best alternative for histology to monitor progression (or non-progression) of suspected (probable) to definite CP. The pathomechanism of pain in CP is multifactorial and data from different series are hardly comparable mainly because insufficient data of the various variables ie diagnosis, classification, staging of CP, pain pattern and presumptive pain cause, are provided. Pain in CP is rarely intractable except in the presence of cancer, opiate addiction or extra-pancreatic pain causes. Local complications like pseudocysts or obstructive cholestasis are the most common causes of severe persistent pain which can be relieved promptly by an appropriate drainage procedure. Notably, partial to complete pain relief is a common feature in 50-80% of patients with late-stage CP irrespective of surgery and about 50% of CP-patients never need surgery (or endoscopic intervention). The spontaneous "burn

  11. Is pancreatic exocrine insufficiency in celiac disease related to structural alterations in pancreatic parenchyma?

    PubMed Central

    Rana, Surinder S.; Dambalkar, Arvind; Chhabra, Puneet; Sharma, Ravi; Nada, Ritambhra; Sharma, Vishal; Rana, Satyavati; Bhasin, Deepak K.

    2016-01-01

    Background Although exocrine pancreatic insufficiency (EPI) has been reported in a number of patients with celiac disease (CD), it is not clear if this is primarily a functional or a structural defect. We studied pancreatic structural abnormalities by endoscopic ultrasound (EUS) in adult CD patients with EPI. Methods Pancreatic exocrine function was prospectively assessed in 36 recently diagnosed CD patients (mean age: 29.8 years) by measuring fecal elastase. Pancreatic structural changes were assessed in CD patients with EPI by EUS and elastography. Exocrine functions were reassessed after 3 months of gluten-free diet. Results Of the 36 CD patients included, 30 (83%) had anemia, 21 (58%) diarrhea, and 7 (19%) hypothyroidism. Ten (28%) patients had EPI with mean elastase levels of 141.6 μg/g of stool, of whom only one had a history of recurrent acute pancreatitis while the rest 9 patients had no history of acute or chronic pancreatitis. Of these 10 patients, 8 (80%) had diarrhea, 8 (80%) anemia, and 2 (20%) hypothyroidism. EUS was done in 8 patients which showed: normal pancreas in 5 (50%), hyperechoic strands in 3 (30%), and hyperechoic foci without shadowing in 2 (20%) patients. None had lobularity or parenchymal calcification. All patients except the patient with recurrent pancreatitis had normal strain ratio. Follow-up fecal elastase was within normal range in 6 of 7 (86%) patients. Conclusion EPI, assessed by fecal elastase levels in adult CD patients, possibly does not relate to structural alterations in the pancreatic parenchyma and may be reversible by following a gluten-free diet. PMID:27366039

  12. Validation of Cardiovascular Parameters during NASA's Functional Task Test

    NASA Technical Reports Server (NTRS)

    Arzeno, N. M.; Stenger, M. B.; Bloomberg, J. J.; Platts, S. H.

    2009-01-01

    Microgravity exposure causes physiological deconditioning and impairs crewmember task performance. The Functional Task Test (FTT) is designed to correlate these physiological changes to performance in a series of operationally-relevant tasks. One of these, the Recovery from Fall/Stand Test (RFST), tests both the ability to recover from a prone position and cardiovascular responses to orthostasis. PURPOSE: Three minutes were chosen for the duration of this test, yet it is unknown if this is long enough to induce cardiovascular responses similar to the operational 5 min stand test. The purpose of this study was to determine the validity and reliability of heart rate variability (HRV) analysis of a 3 min stand and to examine the effect of spaceflight on these measures. METHODS: To determine the validity of using 3 vs. 5 min of standing to assess HRV, ECG was collected from 7 healthy subjects who participated in a 6 min RFST. Mean R-R interval (RR) and spectral HRV were measured in minutes 0-3 and 0-5 following the heart rate transient due to standing. Significant differences between the segments were determined by a paired t-test. To determine the reliability of the 3-min stand test, 13 healthy subjects completed 3 trials of the FTT on separate days, including the RFST with a 3 min stand. Analysis of variance (ANOVA) was performed on the HRV measures. One crewmember completed the FTT before a 14-day mission, on landing day (R+0) and one (R+1) day after returning to Earth. RESULTS VALIDITY: HRV measures reflecting autonomic activity were not significantly different during the 0-3 and 0-5 min segments. RELIABILITY: The average coefficient of variation for RR, systolic (SBP) and diastolic blood pressures during the RFST were less than 8% for the 3 sessions. ANOVA results yielded a greater inter-subject variability (p<0.006) than inter-session variability (p>0.05) for HRV in the RFST. SPACEFLIGHT: Lower RR and higher SBP were observed on R+0 in rest and stand. On R+1

  13. Development of additional tasks for the executive function performance test.

    PubMed

    Hahn, Bridget; Baum, Carolyn; Moore, Jennifer; Ehrlich-Jones, Linda; Spoeri, Susan; Doherty, Meghan; Wolf, Timothy J

    2014-01-01

    OBJECTIVE. The Executive Function Performance Test (EFPT) is a reliable and valid performance-based assessment of executive function for people with stroke. The objective of this study was to enhance the clinical utility of the EFPT by developing and testing additional tasks for the EFPT in the Alternate EFPT (aEFPT). METHOD. We performed a cross-sectional study with poststroke participants (n = 25) and healthy control participants (n = 25). All participants completed a neuropsychological assessment battery and both the EFPT and the aEFPT. RESULTS. No statistically significant differences were found between the EFPT and the aEFPT when examining total scores, construct scores, and two overall task scores. Correlations between the aEFPT and the neuropsychological measures were adequate to strong (r2s = .59-.83). CONCLUSION. The aEFPT tasks are comparable to the original EFPT tasks, providing occupational therapy practitioners with additional tasks that can be used clinically to identify performance-based executive function deficits in people with stroke. PMID:25397771

  14. Study on Noncontact Pulmonary Function Test Using Pattern Light Projection

    NASA Astrophysics Data System (ADS)

    Aoki, Hirooki; Koshiji, Kohji

    The pulmonary function test by spirometer is generally conducted. The test subjects, especially children, women and older people, feel uncomfortable as the mouthpiece and nasal plug must be attached to the face of them. We have studied the nonrestraint pulmonary function test using the dot matrix pattern projection in order to decrease the burden to the examinee. In our proposed system, the pattern light projector illuminates the thorax with the dot matrix pattern light. And the CCD camera takes a series of images of the dot matrix pattern. The three dimensional shape of the thorax surface can be calculated by the distribution of light dots. And the respiratory waveform is calculated by the time-series change of the three dimensional shape. The respiratory waveform of our system was similar to one of spirometer. Therefore, we clarified that our proposed system can equivalently measure the respiration with spirometer. And we compared the volume change of the three dimensional shape calculated by our system with the expired tidal volume measured by the expiration gas analyzer. And we examined the relationship between the expired tidal volume and the volume change of the thorax surface.

  15. Assessment of pulmonary function tests in cardiac patients.

    PubMed

    El-Sobkey, Salwa B; Gomaa, Magdi

    2011-04-01

    This study was aimed to assess the pulmonary function tests (PFTs) in cardiac patients; with ischemic or rheumatic heart diseases as well as in patients who underwent coronary artery bypass graft (CABG) or valvular procedures. For the forty eligible participants, the pulmonary function was measured using the spirometry test before and after the cardiac surgery. Data collection sheet was used for the patient's demographic and intra-operative information. Cardiac diseases and surgeries had restrictive negative impact on PFTs. Before surgery, vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), ratio between FEV1 and FVC, and maximum voluntary ventilation (MVV) recorded lower values for rheumatic patients than ischemic patients (P values were 0.01, 0.005, 0.0001, 0.031, and 0.035, respectively). Moreover, patients who underwent valvular surgery had lower PFTs than patients who underwent CABG with significant differences for VC, FVC, FEV1, and MVV tests (P values were 0.043, 0.011, 0.040, and 0.020, respectively). No definite causative factor appeared to be responsible for those results although mechanical deficiency and incisional chest pain caused by cardiac surgery are doubtful. More comprehensive investigation is required to resolve the case. PMID:23960642

  16. Post-ERCP pancreatitis.

    PubMed

    Arata, Shinju; Takada, Tadahiro; Hirata, Koichi; Yoshida, Masahiro; Mayumi, Toshihiko; Hirota, Morihisa; Yokoe, Masamichi; Hirota, Masahiko; Kiriyama, Seiki; Sekimoto, Miho; Amano, Hodaka; Wada, Keita; Kimura, Yasutoshi; Gabata, Toshifumi; Takeda, Kazunori; Kataoka, Keisho; Ito, Tetsuhide; Tanaka, Masao

    2010-01-01

    Pancreatitis remains the most common severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Detailed information about the findings of previous studies concerning post-ERCP pancreatitis has not been utilized sufficiently. The purpose of the present article was to present guidelines for the diagnostic criteria of post-ERCP pancreatitis, and its incidence, risk factors, and prophylactic procedures that are supported by evidence. To achieve this purpose, a critical examination was made of the articles on post-ERCP pancreatitis, based on the data obtained by research studies published up to 2009. At present, there are no standardized diagnostic criteria for post-ERCP pancreatitis. It is appropriate that post-ERCP pancreatitis is defined as acute pancreatitis that has developed following ERCP, and its diagnosis and severity assessment should be made according to the diagnostic criteria and severity assessment of the Japanese Ministry of Health, Labour and Welfare. The incidence of acute pancreatitis associated with diagnostic and therapeutic ERCP is 0.4-1.5 and 1.6-5.4%, respectively. Endoscopic papillary balloon dilation is associated with a high risk of acute pancreatitis compared with endoscopic sphincterotomy. It was made clear that important risk factors include dysfunction of the Oddi sphincter, being of the female sex, past history of post-ERCP pancreatitis, and performance of pancreaticography. Temporary prophylactic placement of pancreatic stents in the high-risk group is useful for the prevention of post-ERCP pancreatitis [odds ratio (OR) 3.2, 95% confidence interval (CI) 1.6-6.4, number needed to treat (NNT) 10]. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduction in the development of post-ERCP pancreatitis (OR 0.46, 95% CI 0.32-0.65). Single rectal administration of NSAIDs is useful for the prevention of post-ERCP pancreatitis [relative risk (RR) 0.36, 95% CI 0.22-0.60, NNT 15] and decreases the

  17. Exercise-induced alterations in pancreatic oxidative stress and mitochondrial function in type 2 diabetic Goto-Kakizaki rats.

    PubMed

    Raza, Haider; John, Annie; Shafarin, Jasmin; Howarth, Frank C

    2016-04-01

    Progressive metabolic complications accompanied by oxidative stress are the hallmarks of type 2 diabetes. The precise molecular mechanisms of the disease complications, however, remain elusive. Exercise-induced nontherapeutic management of type 2 diabetes is the first line of choice to control hyperglycemia and diabetes associated complications. In this study, using 11-month-old type 2 Goto-Kakizaki (GK) rats, we have investigated the effects of exercise on mitochondrial metabolic and oxidative stress in the pancreas. Our results showed an increase in theNADPHoxidase enzyme activity and reactive oxygen species (ROS) production inGKrats, which was inhibited after exercise. Increased lipid peroxidation and protein carbonylation andSODactivity were also inhibited after exercise. Interestingly, glutathione (GSH) level was markedly high in the pancreas ofGKdiabetic rats even after exercise. However,GSH-peroxidase andGSH-reductase activities were significantly reduced. Exercise also induced energy metabolism as observed by increased hexokinase and glutamate dehydrogenase activities. A significant decrease in the activities of mitochondrial ComplexesII/IIIandIVwere observed in theGKrats. Exercise improved only ComplexIVactivity suggesting increased utilization of oxygen. We also observed increased activities of cytochrome P450s in the pancreas ofGKrats which was reduced significantly after exercise.SDS-PAGEresults have shown a decreased expression ofNF-κB, Glut-2, andPPAR-ϒ inGKrats which was markedly increased after exercise. These results suggest differential oxidative stress and antioxidant defense responses after exercise. Our results also suggest improved mitochondrial function and energy utilization in the pancreas of exercisingGKrats. PMID:27095835

  18. Hippo transducer TAZ promotes epithelial mesenchymal transition and supports pancreatic cancer progression

    PubMed Central

    Xie, Dacheng; Cui, Jiujie; Xia, Tian; Jia, Zhiliang; Wang, Liang; Wei, Wenfei; Zhu, Anna; Gao, Yong; Xie, Keping; Quan, Ming

    2015-01-01

    Transcriptional co-activator with PDZ binding motif (TAZ) is a transducer of the Hippo pathway and promotes cancer development and progression. In the present study, we sought to determine the roles and underlying mechanisms of elevated expression and activation of TAZ in pancreatic cancer development and progression. The mechanistic role of TAZ and Hippo signaling in promotion of pancreatic cancer development and progression was examined using cell culture, molecular biology, and mouse models. The relevance of our experimental and mechanistic findings was validated using human pancreatic tumor specimens. We found that TAZ expression was markedly higher in pancreatic tumors than in normal pancreatic tissue. Further analysis of the correlation of TAZ expression with tissue microarray clinicopathologic parameters revealed that this expression was positively associated with tumor differentiation. Also, TAZ expression was higher in pancreatic cancer cell lines than in pancreatic ductal epithelial cells. TAZ activation in pancreatic cancer cells promoted their proliferation, migration, invasion, and epithelial-mesenchymal transition. Further mechanistic studies demonstrated that aberrant expression and activation of TAZ in pancreatic cancer cells resulted from suppression of the expression of Merlin, a positive regulator upstream of the Hippo pathway, and that the oncogenic function of TAZ in pancreatic cancer cells was mediated by TEA/ATTS domain transcription factors. Therefore, TAZ functioned as an oncogene and promoted pancreatic cancer epithelial-mesenchymal transition and progression. TAZ thus may be a target for effective therapeutic strategies for pancreatic cancer. PMID:26416426

  19. Autonomic function testing aboard the ISS using “PNEUMOCARD”

    NASA Astrophysics Data System (ADS)

    Baevsky, R. M.; Funtova, I. I.; Diedrich, A.; Chernikova, A. G.; Drescher, J.; Baranov, V. M.; Tank, J.

    2009-10-01

    Investigations of blood pressure, heart rate (HR), and heart rate variability (HRV) during long term space flights on board the "ISS" have shown characteristic changes of autonomic cardiovascular control. Therefore, alterations of the autonomic nervous system occurring during spaceflight may be responsible for in- and post-flight disturbances. The device "Pneumocard" was developed to further investigate autonomic cardiovascular and respiratory function aboard the ISS. The hard-software diagnostic complex "Pneumocard" was used during in-flight experiment aboard ISS for autonomic function testing. ECG, photoplethysmography, respiration, transthoracic bioimpedance and seismocardiography were assessed in one male cosmonaut (flight lengths six month). Recordings were made prior to the flight, late during flight, and post-flight during spontaneous respiration and controlled respiration at different rates. HR remained stable during flight. The values were comparable to supine measurements on earth. Respiratory frequency and blood pressure decreased during flight. Post flight HR and BP values increased compared to in-flight data exceeding pre-flight values. Cardiac time intervals did not change dramatically during flight. Pulse wave transit time decreased during flight. The maximum of the first time derivative of the impedance cardiogram, which is highly correlated with stroke volume was not reduced in-flight. Our results demonstrate that autonomic function testing aboard the ISS using "Pneumocard" is feasible and generates data of good quality. Despite the decrease in BP, pulse wave transit time was found reduced in space as shown earlier. However, cardiac output did not decrease profoundly in the investigated cosmonaut. Autonomic testing during space flight detects individual changes in cardiovascular control and may add important information to standard medical control. The recent plans to support a flight to Mars, makes these kinds of observations all the more relevant

  20. Pulmonary function testing and pulmonary Langerhans cell histiocytosis.

    PubMed

    Bernstrand, Cecilia; Cederlund, Kerstin; Henter, Jan-Inge

    2007-09-01

    In a long-term single-center follow-up (median 16-years), we studied high-resolution computed tomography (HRCT) and pulmonary function testing (PFT) in pulmonary LCH. Diffusing capacity corrected for alveolar volume (K(CO)) and total lung capacity (TLC) were significantly decreased (P=0.016 and P=0.030, respectively) in patients with extensive HRCT abnormalities. Patients with late stage disease on HRCT had increased forced expiratory volume (FEV1.0)(P=0.037) and vital capacity (VC)(P=0.036). Disease monitoring is important in pulmonary LCH, and since PFT with diffusing capacity provides a measurement of the current lung function, it may be a valuable tool in monitoring pulmonary LCH, and a good complement to imaging. PMID:16317743

  1. Use of the argon aiming beam in visual function testing.

    PubMed

    Kelley, J S

    1978-12-01

    The aiming beam of the argon laser photocoagulator can be a useful tool in visual function testing. Applied with the slit lamp delivery system and fundus contact lens, it clearly documents the size of the blind spot surrounding the optic nerve head and the normal area of nonfunctional retina in the periphery. The size of pathologic field defects can be recorded on fundus photographs or retinal drawings by an observer. Safety precautions must be taken to protect all patients from excessive laser energy. PMID:736394

  2. Pulmonary physiology: future directions for lung function testing in COPD.

    PubMed

    Brusasco, Vito; Barisione, Giovanni; Crimi, Emanuele

    2015-02-01

    Chronic obstructive pulmonary disease (COPD) is a term that encompasses different pathological conditions having excessive airflow limitation in common. A wide body of knowledge has been accumulated over the last century explaining the mechanisms by which airway (chronic bronchitis) and parenchymal (emphysema) diseases lead to an indistinguishable spirometric abnormality. Although the definition of emphysema is anatomical, early studies showed that its presence can be inferred with good approximation from measurements of lung mechanics and gas exchange, in addition to simple spirometry. Studies using tests of ventilation distribution showed that abnormalities are present in smokers with normal spirometry, although these tests were not predictive of development of COPD. At the beginning of the third millennium, new documents and guidelines for diagnosis and treatment of COPD were developed, in which the functional diagnosis of COPD was restricted, for the sake of simplicity, to simple spirometry. In recent years, there has been a resurgence of interest in separating bronchitic from emphysematous phenotype of COPD. For this purpose, high-resolution computed tomography scanning has been added to diagnostic work-up. At the same time, methods for lung function testing have been refined and seem promising for detection of early small airways abnormalities. Among them are the forced oscillation technique and the nitrogen phase III slope analysis of the multiple-breath washout test, which may provide information on ventilation inhomogeneity. Moreover, the combined assessment of diffusing capacity for nitric oxide and carbon monoxide may be more sensitive than the latter alone for partitioning diffusive components at parenchymal level. PMID:25257934

  3. Molecular network, pathway, and functional analysis of time-dependent gene changes associated with pancreatic cancer susceptibility to oncolytic vaccinia virotherapy

    PubMed Central

    Haddad, Dana; Socci, Nicholas; Chen, Chun-Hao; Chen, Nanhai G; Zhang, Qian; Carpenter, Susanne G; Mittra, Arjun; Szalay, Aladar A; Fong, Yuman

    2016-01-01

    Background: Pancreatic cancer is a fatal disease associated with resistance to conventional therapies. This study aimed to determine changes in gene expression patterns associated with infection and susceptibility of pancreatic cancer cells to an oncolyticvaccinia virus, GLV-1h153, carrying the human sodium iodide symporter for deep tissue imaging of virotherapy. Methods: Replication and susceptibility of pancreatic adenocarcinoma PANC-1 cells to GLV-1h153 was confirmed with replication and cytotoxicity assays. PANC-1 cells were then infected with GLV-1h153 and near-synchronous infection confirmed via flow cytometry of viral-induced green fluorescent protein (GFP) expression. Six and 24 hours after infection, three samples of each time point were harvested, and gene expression patterns assessed using HG-U133A cDNA microarray chips as compared to uninfected control. Differentially expressed genes were identified using Bioconductor LIMMA statistical analysis package. A fold change of 2.0 or above was used as a cutoff, with a P value of 0.01. The gene list was then analyzed using Ingenuity Pathways Analysis software. Results: Differential gene analysis revealed a total of 12,412 up- and 11,065 downregulated genes at 6 and 24 hours postinfection with GLV-1h153 as compared to control. At 6 hours postinfection. A total of 139 genes were either up or downregulated >twofold (false discovery rate < 0.05), of which 124 were mapped by Ingenuity Pathway Analysis (IPA). By 24 hours postinfection, a total of 5,698 genes were identified and 5,563 mapped by IPA. Microarray revealed gene expression changes, with gene networks demonstrating downregulation of processes such as cell death, cell cycle, and DNA repair, and upregulation of infection mechanisms (P < 0.01). Six hours after infection, gene changes involved pathways such as HMGB-1, interleukin (IL)-2, IL-6, IL-8, janus kinase/signal tranducer and activator of transcription (JAK/STAT), interferon, and ERK 5 signaling (P < 0

  4. [Etiological factors of acute pancreatitis].

    PubMed

    Spicák, J

    2002-09-01

    Acute pancreatitis develops immediately after the causative impulse, while chronic pancreatitis develops after the long-term action of the noxious agent. A typical representative of acute pancreatitis is biliary pancreatitis, chronic pancreatitis develops in alcoholism and has a long latency. As alcoholic pancreatitis is manifested at first as a rule by a potent attack, it is classified in this stage as acute pancreatitis. The most frequent etiological factors in our civilization are thus cholelithiasis and alcoholism (both account for 20-50% in different studies). The assumed pathogenetic principles in acute biliary pancreatitis are the common canal of both efferent ducts above the obturated papilla, duodenopancreatic reflux and intrapancreatic hypertension. A detailed interpretation is however lacking. The pathogenesis of alcoholic pancreatitis is more complicated. Among others some part is played by changes in the calcium concentration and fusion of cellular membranes. Idiopathic pancreatitis occurs in up to 10%, part of the are due to undiagnosed alcoholism and cholelithiasis. Other etiologies are exceptional. Similarly as in cholelithiasis pancreatitis develops also during other pathological processes in the area of the papilla of Vater such as dysfunction of the sphincter of Oddi, ampulloma and juxtapapillary diverticulum, it is however usually mild. The incidence of postoperative pancreatitis is declining. Its lethality is 30% and the diagnosis is difficult. In the pathogenesis changes of the ion concentration are involved, hypoxia and mechanical disorders of the integrity of the gland. Pancreatitis develops in association with other infections--frequently in mumps, rarely in hepatitis, tuberculosis, typhoid and mycoses. Viral pancreatitis is usually mild. In parasitoses pancreatitis develops due to a block of the papilla Vateri. In hyperparathyroidism chronic pancreatitis is more likely to develop, recent data are lacking. As to dyslipoproteinaemias

  5. Intra-abdominal hypertension and acute pancreatitis.

    PubMed

    Mifkovic, A; Skultety, J; Sykora, P; Prochotsky, A; Okolicany, R

    2013-01-01

    Intra-abdominal hypertension (IAH) contributes to organ dysfunction and leads to the development of the abdominal compartment syndrome (ACS). IAH and ACS are relatively frequent findings in patiens with severe acute pancreatitis (SAP) and are associated with deterioration in organ functions. The most affected are cardiovascular, respiratory and renal functions. The incidence of IAH in patients with SAP is approximately 60-80%. There is an accumulating evidence in human and animal studies that changes of perfusion, particularly to the microvasculature, are crucial events in the progression of acute pancreatitis (AP). The perfusion of the small and large intestine is impaired due to reduced arterial pressure, increased vascular resistence and diminished portal blood flow. Bacterial translocation has been described in patients with ACS, and this may apply to patients with SAP. Approximately 30-40% of SAP patients develop ACS because of pancreatic (retroperitoneal) inflammation, peripancreatic tissue edema, formation of fluid collections or abdominal distension. Surgical debridement was the preferred treatment to control necrotizing pancreatitis in the past. However, the management of necrotizing pancreatitis has changed over the last decade. The main objective of this article is to describe the association between IAH and AP and to emphasize this situation in clinical praxis as well (Fig. 1, Ref. 38). PMID:23406186

  6. Magnetic resonance imaging in the detection of pancreatic neoplasms.

    PubMed

    Zhong, Liang

    2007-08-01

    Recently, with the rapid scanning time and improved image quality, outstanding advances in magnetic resonance (MR) methods have resulted in an increase in the use of MRI for patients with a variety of pancreatic neoplasms. MR multi-imaging protocol, which includes MR cross-sectional imaging, MR cholangiopancreatography and dynamic contrast-enhanced MR angiography, integrates the advantages of various special imaging techniques. The non-invasive all-in-one MR multi-imaging techniques may provide the comprehensive information needed for the preoperative diagnosis and evaluation of pancreatic neoplasms. Pancreatic neoplasms include primary tumors and pancreatic metastases. Primary tumors of the pancreas may be mainly classified as ductal adenocarcinomas, cystic tumors and islet cell tumors (ICT). Pancreatic adenocarcinomas can be diagnosed in a MRI study depending on direct evidence or both direct and indirect evidence. The combined MRI features of a focal pancreatic mass, pancreatic duct dilatation and parenchymal atrophy are highly suggestive of a ductal adenocarcinoma. Most cystic neoplasms of the pancreas are either microcystic adenomas or mucinous cystic neoplasms. Intraductal papillary mucinous tumors are the uncommon low-grade malignancy of the pancreatic duct. ICT are rare neoplasms arising from neuroendocrine cells in the pancreas or the periampullary region. ICT are classified as functioning and non-functioning. The most frequent tumors to metastasize to the pancreas are cancers of the breast, lung, kidney and melanoma. The majority of metastases present as large solitary masses with well-defined margins. PMID:17650223

  7. Uncommon presentations of common pancreatic neoplasms: a pictorial essay.

    PubMed

    D'Onofrio, Mirko; De Robertis, Riccardo; Capelli, Paola; Tinazzi Martini, Paolo; Crosara, Stefano; Gobbo, Stefano; Butturini, Giovanni; Salvia, Roberto; Barbi, Emilio; Girelli, Roberto; Bassi, Claudio; Pederzoli, Paolo

    2015-08-01

    Pancreatic neoplasms are a wide group of solid and cystic lesions with different and often characteristic imaging features, clinical presentations, and management. Among solid tumors, ductal adenocarcinoma is the most common: it arises from exocrine pancreas, comprises about 90% of all pancreatic neoplasms, and generally has a bad prognosis; its therapeutic management must be multidisciplinary, involving surgeons, oncologists, gastroenterologists, radiologists, and radiotherapists. The second most common solid pancreatic neoplasms are neuroendocrine tumors: they can be divided into functioning or non-functioning and present different degrees of malignancy. Cystic pancreatic neoplasms comprise serous neoplasms, which are almost always benign, mucinous cystic neoplasms and intraductal papillary mucinous neoplasms, which can vary from benign to frankly malignant lesions, and solid pseudopapillary tumors. Other pancreatic neoplasms, such as lymphoma, metastases, or pancreatoblastoma, are rarely seen in clinical practice and have different and sometimes controversial managements. Rare clinical presentations and imaging appearance of the most common pancreatic neoplasms, both solid and cystic, are more frequently seen and clinically relevant than rare pancreatic tumors; their pathologic and radiologic appearances must be known to improve their management. The purpose of this paper is to present some rare or uncommon clinical and radiological presentations of common pancreatic neoplasms providing examples of multi-modality imaging approach with pathologic correlations, thus describing the histopathological bases that can explain the peculiar imaging features, in order to avoid relevant misdiagnosis and to improve lesion management. PMID:25772002

  8. Human pancreatic cancer fusion 2 (HPC2) 1-B3: a novel monoclonal antibody to screen for pancreatic ductal dysplasia.

    PubMed

    Morgan, Terry K; Hardiman, Karin; Corless, Christopher L; White, Sandra L; Bonnah, Robert; Van de Vrugt, Henry; Sheppard, Brett C; Grompe, Markus; Cosar, Ediz F; Streeter, Philip R

    2013-01-01

    BACKGROUND.: Pancreatic ductal adenocarcinoma is rarely detected early enough for patients to be cured. The objective of the authors was to develop a monoclonal antibody to distinguish adenocarcinoma and precancerous intraductal papillary mucinous neoplasia (IPMN) from benign epithelium. METHODS.: Mice were immunized with human pancreatic adenocarcinoma cells and monoclonal antibodies were screened against a panel of archived pancreatic tissue sections, including pancreatitis (23 cases), grade 1 IPMN (16 cases), grade 2 IPMN (9 cases), grade 3 IPMN (13 cases), and various grades of adenocarcinoma (17 cases). One monoclonal antibody, human pancreatic cancer fusion 2 (HPC2) 1-B3, which specifically immunostained adenocarcinoma and all grades of IPMN, was isolated. Subsequently, HPC2 1-B3 was evaluated in a retrospective series of 31 fine-needle aspiration (FNA) biopsies from clinically suspicious pancreatic lesions that had long-term clinical follow-up. RESULTS.: HPC2 1-B3 was negative in all 31 cases of chronic pancreatitis that were tested. In contrast, HPC2 1-B3 immunostained the cytoplasm and luminal surface of all 16 well- to moderately differentiated pancreatic ductal adenocarcinomas. It demonstrated only weak focal staining of poorly differentiated carcinomas. All high-grade IPMNs were found to be positive for HPC2 1-B3. The majority of low-grade to intermediate-grade IPMNs were positive (66% of cases). Immunostaining a separate series of pancreatic FNA cell blocks for HPC2 1-B3 demonstrated that the relative risk for detecting at least low-grade dysplasia (2.0 [95% confidence interval, 1.23-3.26]) was statistically significant (P = .002 by the Fisher exact test). CONCLUSIONS.: To reduce the mortality of pancreatic cancer, more effective early screening methods are necessary. The data from the current study indicate that a novel monoclonal antibody, HPC2 1-B3, may facilitate the diagnosis of early pancreatic dysplasia. PMID:22811080

  9. TRL - A FORMAL TEST REPRESENTATION LANGUAGE AND TOOL FOR FUNCTIONAL TEST DESIGNS

    NASA Technical Reports Server (NTRS)

    Hops, J. M.

    1994-01-01

    A Formal Test Representation Language and Tool for Functional Test Designs (TRL) is an automatic tool and a formal language that is used to implement the Category-Partition Method and produce the specification of test cases in the testing phase of software development. The Category-Partition Method is particularly useful in defining the inputs, outputs and purpose of the test design phase and combines the benefits of choosing normal cases with error exposing properties. Traceability can be maintained quite easily by creating a test design for each objective in the test plan. The effort to transform the test cases into procedures is simplified by using an automatic tool to create the cases based on the test design. The method allows the rapid elimination of undesired test cases from consideration, and easy review of test designs by peer groups. The first step in the category-partition method is functional decomposition, in which the specification and/or requirements are decomposed into functional units that can be tested independently. A secondary purpose of this step is to identify the parameters that affect the behavior of the system for each functional unit. The second step, category analysis, carries the work done in the previous step further by determining the properties or sub-properties of the parameters that would make the system behave in different ways. The designer should analyze the requirements to determine the features or categories of each parameter and how the system may behave if the category were to vary its value. If the parameter undergoing refinement is a data-item, then categories of this data-item may be any of its attributes, such as type, size, value, units, frequency of change, or source. After all the categories for the parameters of the functional unit have been determined, the next step is to partition each category's range space into mutually exclusive values that the category can assume. In choosing partition values, all possible kinds

  10. Highly adaptive tests for group differences in brain functional connectivity.

    PubMed

    Kim, Junghi; Pan, Wei

    2015-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) and other technologies have been offering evidence and insights showing that altered brain functional networks are associated with neurological illnesses such as Alzheimer's disease. Exploring brain networks of clinical populations compared to those of controls would be a key inquiry to reveal underlying neurological processes related to such illnesses. For such a purpose, group-level inference is a necessary first step in order to establish whether there are any genuinely disrupted brain subnetworks. Such an analysis is also challenging due to the high dimensionality of the parameters in a network model and high noise levels in neuroimaging data. We are still in the early stage of method development as highlighted by Varoquaux and Craddock (2013) that "there is currently no unique solution, but a spectrum of related methods and analytical strategies" to learn and compare brain connectivity. In practice the important issue of how to choose several critical parameters in estimating a network, such as what association measure to use and what is the sparsity of the estimated network, has not been carefully addressed, largely because the answers are unknown yet. For example, even though the choice of tuning parameters in model estimation has been extensively discussed in the literature, as to be shown here, an optimal choice of a parameter for network estimation may not be optimal in the current context of hypothesis testing. Arbitrarily choosing or mis-specifying such parameters may lead to extremely low-powered tests. Here we develop highly adaptive tests to detect group differences in brain connectivity while accounting for unknown optimal choices of some tuning parameters. The proposed tests combine statistical evidence against a null hypothesis from multiple sources across a range of plausible tuning parameter values reflecting uncertainty with the unknown truth. These highly adaptive tests are not only

  11. Highly adaptive tests for group differences in brain functional connectivity

    PubMed Central

    Kim, Junghi; Pan, Wei

    2015-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) and other technologies have been offering evidence and insights showing that altered brain functional networks are associated with neurological illnesses such as Alzheimer's disease. Exploring brain networks of clinical populations compared to those of controls would be a key inquiry to reveal underlying neurological processes related to such illnesses. For such a purpose, group-level inference is a necessary first step in order to establish whether there are any genuinely disrupted brain subnetworks. Such an analysis is also challenging due to the high dimensionality of the parameters in a network model and high noise levels in neuroimaging data. We are still in the early stage of method development as highlighted by Varoquaux and Craddock (2013) that “there is currently no unique solution, but a spectrum of related methods and analytical strategies” to learn and compare brain connectivity. In practice the important issue of how to choose several critical parameters in estimating a network, such as what association measure to use and what is the sparsity of the estimated network, has not been carefully addressed, largely because the answers are unknown yet. For example, even though the choice of tuning parameters in model estimation has been extensively discussed in the literature, as to be shown here, an optimal choice of a parameter for network estimation may not be optimal in the current context of hypothesis testing. Arbitrarily choosing or mis-specifying such parameters may lead to extremely low-powered tests. Here we develop highly adaptive tests to detect group differences in brain connectivity while accounting for unknown optimal choices of some tuning parameters. The proposed tests combine statistical evidence against a null hypothesis from multiple sources across a range of plausible tuning parameter values reflecting uncertainty with the unknown truth. These highly adaptive tests are not

  12. Pancreatic body hydatid cyst: A case report

    PubMed Central

    Sorogy, Mohamed El; El-Hemaly, Mohamed; Aboelenen, Ahmed

    2014-01-01

    INTRODUCTION Hydatid disease is a parasitic infestation caused by the cystic stage of Echinococcus granulosus. Hydatid cysts are commonly located in the liver and lung. Pancreatic affection by hydatid cysts is very rare even in endemic areas. PRESENTATION OF CASE Our case is a 34-year-old male patient referred to our centre with a pancreatic body cyst diagnosed by abdominal CT scan. The patient gave 3 months history of epigastric pain. He also gave history of travelling to Saudi Arabia and China. His enzyme-linked immunoadsorbent assay (ELIZA) test for echinococcal antigens was positive. Surgical exploration revealed a 7 cm cyst in the body of the pancreas separable from the surroundings. Endocystectomy and deroofing of the cyst was done. DISCUSSION Due to its rarity and similarity with more common pancreatic cystic conditions, diagnosis of pancreatic hydatid cyst may be challenging. Abdmonial sonography and CT scan together with enzyme-linked immunoadsorbent assay (ELIZA) test for echinococcal antigens are helpful diagnostic tools. Therapeutic options include endocystectomy and deroofing, albendazol therapy with percutaneous drainage or laparoscopic excision of the cyst. CONCLUSION Even in non-endemic areas, past history of travelling abroad in patients with pancreatic cystic lesions should raise the suspicion of hydatid disease as a possible diagnosis. PMID:25528027

  13. Validation of a Computerized test of Functional Capacity.

    PubMed

    Keefe, Richard S E; Davis, Vicki G; Atkins, Alexandra S; Vaughan, Adam; Patterson, Tom; Narasimhan, Meera; Harvey, Philip D

    2016-08-01

    Regulatory guidance for schizophrenia cognition clinical trials requires that the assessment of cognitive change is accompanied by a functionally meaningful endpoint. However, currently available measures are challenged by resistance to change, psychometric weaknesses, and for interview-based assessments, dependence upon the presence of an informant. The aims of the current study were to: 1) assess the validity, sensitivity, and reliability of the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) as a measure of functional capacity; 2) determine the association between performance on the VRFCAT and performance on the MATRICS Consensus Cognitive Battery (MCCB); and 3) compare the metrics of the VRFCAT with the UCSD Performance-based Skills Assessment (UPSA). 167 patients with schizophrenia and 166 healthy controls completed the VRFCAT, UPSA, and the MCCB at baseline. The VRFCAT and UPSA were completed again at follow-up. The VRFCAT, MCCB, and UPSA were very sensitive to impairment in schizophrenia (d=1.16 to 1.22). High test-retest reliability was demonstrated for VRFCAT total completion time and the UPSA total score in patients (ICC=0.81 and 0.78, respectively). The UPSA demonstrated significant practice effects in patients (d=0.35), while the VRFCAT did not (d=-0.04). VRFCAT total completion time was correlated with both UPSA (r=-0.56, p<0.0001 for patients and -0.58, p<0.0001 for controls) and MCCB Composite (r=-0.57, p<0.0001 for patients and -0.68, p<0.0001 for controls). The VRFCAT is a highly reliable and sensitive measure of functional capacity with associations to the UPSA and MCCB. These results provide encouraging support for a computerized functional capacity assessment for use in schizophrenia. PMID:27091656

  14. SOFIA Telescope Functional Integration and Performance Test Activities

    NASA Astrophysics Data System (ADS)

    Waddell, P.; Haas, M. R.; Dunham, E. W.; Bremers, E.; Harms, F.; Keas, P. J.; Lattner, K.; Lillienthal, D.; Meyer, A. W.; Wolf, J.

    2004-12-01

    The Stratospheric Observatory for Infrared Astronomy (SOFIA) is a 2.7-m telescope installed in a Boeing 747SP. Collaborators developing the SOFIA telescope and observatory completed an intense period of activation between mid-June and mid-August, 2004. The integration activities included a preliminary modal survey; alignment of the Wide Field, Fine Field, and Focal Plane Imagers; installation of the secondary and tertiary mirrors; and their alignment relative to the primary mirror. Once these preliminaries were completed, SOFIA was rolled out of its hangar for a series of ground-based, on-sky tests using HIPO, the first science instrument to be installed on the telescope. First light was achieved observing Polaris on August 18, 2004. The on-sky test period encompassed 12 nights in late August and early September and included telescope step function response and first-order pointing control, image quality and optical tracking stability measurements, evaluation of the tracking imagers, gravity deformation studies, gyro alignment and bias rate measurement and correction, and performance tests of the secondary mirror Focus Centering Mechanism and Tilt Chopping Mechanism. It also included tests of the complete telescope command set, including Image Quality Compensation (IQC), quasi-static Flexible Body Compensation (FBC), reference frame transformations and trajectory estimation algorithms. This poster summarizes the results and describes the expected performance of SOFIA at the start of science observations. SOFIA is jointly funded by NASA and DLR and is managed by USRA and DSI. The successful, on-schedule completion of these tests involved close coordination by these three parties, CSA Engineering, CSEM, Kayser-Threde, L-3 Communications, Lowell Observatory, MAN-Technologies, Orbital Sciences, and others.

  15. Pleuropulmonary complications of pancreatitis

    PubMed Central

    Kaye, Michael D.

    1968-01-01

    Pancreatitis, in common with many other upper abdominal diseases, often leads to pleuropulmonary complications. Radiological evidence of pleuropulmonary abnormality was found in 55% of 58 cases examined retrospectively. The majority of such abnormalities are not specific for pancreatitis; but a particular category of pleural effusions, rich in pancreatic enzymes, is a notable exception. A patient with this type of effusion, complicated by a spontaneous bronchopleural fistula and then by an empyema, is reported. The literature relating to pancreatic enzyme-rich pleural effusions (pathognomonic of pancreatitis) is reviewed. Of several possible mechanisms involved in pathogenesis, transdiaphragmatic lymphatic transfer of pancreatic enzymes, intrapleural rupture of mediastinal extensions of pseudocysts, and diaphragmatic perforation are the most important. The measurement of pleural fluid amylase, at present little employed in this country, has considerable diagnostic value. Enzyme-rich effusions are more commonly left-sided, are often blood-stained, are frequently associated with pancreatic pseudocysts, and—if long standing—may be complicated by a bronchopleural fistula. Images PMID:4872925

  16. Acute Pancreatitis in Children.

    PubMed

    Werlin, Steven L.

    2001-10-01

    There are no drugs that cure or abate pancreatitis. The treatment of patients with mild and moderate episodes of pancreatitis (85%) is supportive and expectant. Central issues include the removal of the initiating process (if possible), relief of pain, and maintenance of fluid and electrolyte balance. Endoscopic retrograde cholangiopancreatography may be required for stone extraction in patients with biliary pancreatitis. Surgery is rarely required. The aims of treatment for patients with severe disease includes treatment of local, systemic, and septic complications in addition to those for mild and moderate disease. Homeostasis is maintained by the correction of hypocalcemia, anemia, hypoalbuminemia, electrolyte imbalances, and hypoxemia. A large number of medications have been used unsuccessfully in an attempt to halt the progression of the autodigestive process within the pancreas and to reduce pancreatic secretions. Nutritional support with either enteral or parenteral feeding is given. Intravenous antibiotics or selective bowel decontamination decrease mortality in patients with severe episodes of pancreatitis. The treatment for these individuals is often prolonged. Surgical treatment of traumatic pancreatitis with ductal rupture includes repair or resection. At times, simple drainage is performed and definitive surgery is deferred until later. Surgical treatment of severe pancreatitis includes debridement of necrotic and infected tissue. The emerging consensus appears to be that necrosectomy and local lavage or open management with planned re-exploration offers better survival than the conventional therapy of resection plus drainage alone. PMID:11560787

  17. Infection control in the pulmonary function test laboratory

    PubMed Central

    Rasam, Shweta Amol; Apte, Komalkirti Keshavkiran; Salvi, Sundeep Santosh

    2015-01-01

    Pulmonary function testing plays a crucial role in the diagnostic evaluation of patients with lung diseases. Cases of cross infection acquired from the pulmonary function laboratory, although rare, have been reported from various countries. It is therefore imperative to identify the risks and potential organisms implicated in cross infections in a pulmonary function test (PFT) laboratory and implement better and more effective infection control procedures, which will help in preventing cross infections. The infrastructure, the daily patient flow, and the prevalent disinfection techniques used in a PFT laboratory, all play a significant role in transmission of infections. Simple measures to tackle the cross infection potential in a PFT laboratory can help reduce this risk to a bare minimum. Use of specialized techniques and equipment can also be of much use in a set up that has a high turnover of patients. This review aims at creating awareness about the possible pathogens and situations commonly encountered in a PFT laboratory. We have attempted to suggest some relevant and useful infection control measures with regard to disinfection, sterilization, and patient planning and segregation to help minimize the risk of cross infections in a PFT laboratory. The review also highlights the lacuna in the current scenario of PFT laboratories in India and the need to develop newer and better methods of infection control, which will be more user-friendly and cost effective. Further studies to study the possible pathogens in a PFT laboratory and evaluate the prevalent infection control strategies will be needed to enable us to draw more precious conclusions, which can lead to more relevant, contextual recommendations for cross infections control in PFT lab in India. PMID:26180386

  18. Functional toxicology: tools to advance the future of toxicity testing.

    PubMed

    Gaytán, Brandon D; Vulpe, Chris D

    2014-01-01

    The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds-information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes. PMID:24847352

  19. Functional toxicology: tools to advance the future of toxicity testing

    PubMed Central

    Gaytán, Brandon D.; Vulpe, Chris D.

    2014-01-01

    The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds—information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes. PMID:24847352

  20. Updates on Functional Characterization of Bronchopulmonary Dysplasia – The Contribution of Lung Function Testing

    PubMed Central

    Greenough, Anne; Pahuja, Anoop

    2015-01-01

    Bronchopulmonary dysplasia (BPD) is a chronic lung disease that predominantly affects prematurely born infants. Initially, BPD was described in infants who had suffered severe respiratory failure and required high pressure, mechanical ventilation with high concentrations of supplementary oxygen. Now, it also occurs in very prematurely born infants who initially had minimal or even no signs of lung disease. These differences impact the nature of the lung function abnormalities suffered by “BPD” infants, which are also influenced by the criteria used to diagnose BPD and the oxygen saturation level used to determine the supplementary oxygen requirement. Key also to interpreting lung function data in this population is whether appropriate lung function tests have been used and in an adequately sized population to make meaningful conclusions. It should also be emphasized that BPD is a poor predictor of long-term respiratory morbidity. Bearing in mind those caveats, studies have consistently demonstrated that infants who develop BPD have low compliance and functional residual capacities and raised resistances in the neonatal period. There is, however, no agreement with regard to which early lung function measurement predicts the development of BPD, likely reflecting different techniques were used in different populations in often underpowered studies. During infancy, lung function generally improves, but importantly airflow limitation persists and small airway function appears to decline. Improvements in lung function following administration of diuretics or bronchodilators have not translated into long-term improvements in respiratory outcomes. By contrast, early differences in lung function related to different ventilation modes have led to investigation and demonstration that prophylactic, neonatal high-frequency oscillation appears to protect small airway function. PMID:26131449

  1. Olfactory functioning in early multiple sclerosis: Sniffin’ Sticks Test study

    PubMed Central

    Batur Caglayan, Hale Z; Irkec, Ceyla; Nazliel, Bijen; Akyol Gurses, Aslı; Capraz, Irem

    2016-01-01

    Introduction Previous studies have shown that olfactory functioning is affected by multiple sclerosis (MS). This study assessed the level of the olfactory impairment in early MS by using the Sniffin’ Sticks Test. Methods This study included 30 patients with MS and 30 healthy controls. We collected demographic and clinical data from participants and administered the Sniffin’ Sticks Test. Results We found no differences between the MS and control groups in odor discrimination, odor identification, and threshold discrimination identification scores, but odor threshold (OT) scores were higher in the control group than in the MS group (P=0.49). In addition, we did not find any correlation between MS patients’ olfactory test scores and their scores on the Mini–Mental State Examination (MMSE), Expanded Disability Status Scale (EDSS), disease duration, history of optic neuritis, or being on immunomodulatory therapy. Conclusion In recent studies, odor threshold impairment seemed to be the most striking finding in patients with MS. Although the present study found a mild alteration in odor threshold, olfactory dysfunction appears to be a consequence of neurodegeneration in the higher order olfactory brain regions, which is thought to be a time-dependent process. PMID:27621629

  2. Functional Task Test: 1. Sensorimotor changes Associated with Postflight Alterations in Astronaut Functional Task Performance

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Arzeno, N. H.; Buxton, R. E.; Feiveson, A. H.; Kofman, I. S.; Lee, S. M. C.; Miller, C. A.; Mulavara, A. P.; Platts, S. H.; Peters, B. T.; Phillips, T.; Ploutz-Snyder, L. L.; Reschke, M. F.; Ryder, J. W.; Spiering, B. A.; Stenger, M. B.; Taylor, L. C.; Wickwire, P. J.; Wood, S. J.

    2011-01-01

    Space flight is known to cause alterations in multiple physiological systems including changes in sensorimotor, cardiovascular, and neuromuscular systems. These changes may affect a crewmember s ability to perform critical mission tasks immediately after landing on a planetary surface. The overall goal of this project is to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. This presentation will focus on the sensorimotor contributions to postflight functional performance.

  3. "Biliary Diseases with Pancreatic Counterparts": Cross-sectional Imaging Findings.

    PubMed

    Katabathina, Venkata S; Flaherty, Erin M; Dasyam, Anil K; Menias, Christine O; Riddle, Nicole D; Lath, Narayan; Kozaka, Kazuto; Matsui, Osamu; Nakanuma, Yasuni; Prasad, Srinivasa R

    2016-01-01

    On the basis of the similarities in the histopathologic findings and the clinical-biologic behaviors of select biliary and pancreatic conditions, a new disease concept, "biliary diseases with pancreatic counterparts," has been proposed. Both nonneoplastic and neoplastic pathologic conditions of the biliary tract have their counterparts in the pancreas. Immunoglobulin G4 (IgG4)-related sclerosing cholangitis is the biliary manifestation of IgG4-related sclerosing disease, and type 1 autoimmune pancreatitis is its pancreatic counterpart. People with chronic alcoholism can develop peribiliary cysts and fibrosis as well as pancreatic fibrosis and chronic pancreatitis simultaneously. Pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm are considered pancreatic counterparts for the biliary neoplasms of extrahepatic cholangiocarcinoma, intraductal papillary neoplasm of the biliary tract, and hepatic mucinous cystic neoplasm, respectively. The anatomic proximity of the biliary tract and the pancreas, the nearly simultaneous development of both organs from the endoderm of the foregut, and the presence of pancreatic exocrine acini within the peribiliary glands surrounding the extrahepatic bile ducts are suggested as causative factors for these similarities. Interestingly, these diseases show "nearly" identical findings at cross-sectional imaging, an observation that further supports this new disease concept. New information obtained with regard to biliary diseases can be used for evaluation of pancreatic abnormalities, and vice versa. In addition, combined genetic and molecular studies may be performed to develop novel therapeutic targets. For both biliary and pancreatic diseases, imaging plays a pivotal role in initial diagnosis, evaluation of treatment response, efficacy testing of novel drugs, and long-term surveillance. PMID:26824512

  4. Potential role of NADPH oxidase in pathogenesis of pancreatitis

    PubMed Central

    Cao, Wei-Li; Xiang, Xiao-Hui; Chen, Kai; Xu, Wei; Xia, Shi-Hai

    2014-01-01

    Studies have demonstrated that reactive oxygen species (ROS) are closely related to inflammatory disorders. Nicotinamide adenine dinucleotide phosphate oxidase (NOX), originally found in phagocytes, is the main source of ROS in nonphagocytic cells. Besides directly producing the detrimental highly reactive ROS to act on biomolecules (lipids, proteins, and nucleic acids), NOX can also activate multiple signal transduction pathways, which regulate cell growth, proliferation, differentiation and apoptosis by producing ROS. Recently, research on pancreatic NOX is no longer limited to inflammatory cells, but extends to the aspect of pancreatic acinar cells and pancreatic stellate cells, which are considered to be potentially associated with pancreatitis. In this review, we summarize the literature on NOX protein structure, activation, function and its role in the pathogenesis of pancreatitis. PMID:25133019

  5. Severe acute pancreatitis: nutritional management in the ICU.

    PubMed

    Kaushik, Neeraj; O'Keefe, Stephen J D

    2004-02-01

    Patients with acute pancreatitis have elevated nutritional needs due to increased energy expenditure and catabolism. It is a clinical challenge to provide adequate nutrition to these patients while maintaining gut function, preventing pancreatic stimulation, and minimizing the risk of septic and metabolic complications associated with nutritional support. We present the case of a patient who had severe acute pancreatitis and was initially given total parenteral nutrition. After a period of initial improvement, he developed hyperglycemia, bacteremia, and sepsis. Parenteral nutrition was discontinued and infection was treated with antibiotics. Subsequent nutritional support consisted of enteral feeding with an elemental diet infused via a nasojejunal feeding tube. His condition improved gradually and he made a full recovery. This case illustrates the difficulties encountered while managing a case of severe acute pancreatitis and provides an evidence based approach to the nutritional management of severe acute pancreatitis in the intensive care unit setting. PMID:16215093

  6. A binuclear complex constituted by diethyldithiocarbamate and copper(I) functions as a proteasome activity inhibitor in pancreatic cancer cultures and xenografts

    SciTech Connect

    Han, Jinbin; Yue, Xiaoqiang; Chang, Jinjia; Shi, Weidong; Hua, Yongqiang

    2013-12-15

    It is a therapeutic strategy for cancers including pancreatic to inhibit proteasome activity. Disulfiram (DSF) may bind copper (Cu) to form a DSF–Cu complex. DSF–Cu is capable of inducing apoptosis in cancer cells by inhibiting proteasome activity. DSF is rapidly converted to diethyldithiocarbamate (DDTC) within bodies. Copper(II) absorbed by bodies is reduced to copper(I) when it enters cells. We found that DDTC and copper(I) could form a binuclear complex which might be entitled DDTC–Cu(I), and it had been synthesized by us in the laboratory. This study is to investigate the anticancer potential of this complex on pancreatic cancer and the possible mechanism. Pancreatic cancer cell lines, SW1990, PANC-1 and BXPC-3 were used for in vitro assays. Female athymic nude mice grown SW1990 xenografts were used as animal models. Cell counting kit-8 (cck-8) assay and flow cytometry were used for analyzing apoptosis in cells. A 20S proteasome assay kit was used in proteasome activity analysis. Western blot (WB) and immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used in tumor sample analysis. The results suggest that DDTC–Cu(I) inhibit pancreatic cancer cell proliferation and proteasome activity in vitro and in vivo. Accumulation of ubiquitinated proteins, and increased p27 as well as decreased NF-κB expression were detected in tumor tissues of DDTC–Cu(I)-treated group. Our data indicates that DDTC–Cu(I) is an effective proteasome activity inhibitor with the potential to be explored as a drug for pancreatic cancer. - Highlights: • A new structure of DDTC–Cu(I) was reported for the first time. • DDTC–Cu(I) dissolved directly in water was for in vitro and in vivo uses. • DDTC–Cu(I) demonstrated significant anticancer effect in vitro and in vivo. • DDTC–Cu(I) is capable of inhibiting proteasome activity in vitro and in vivo.

  7. The nylon column dye test: a possible screening test of phagocyte function.

    PubMed

    Segal, A W; Peters, T J

    1975-12-01

    1. A simple quantitative test has been developed to investigate phagocyte function. 2. This test is performed by the addition of Nitroblue Tetrazolium to whole blood, followed by the isolation of leucocytes on a column of nylon wool. Dye reduction by phagocytes is apparent as a blue coloration of the column due to the formation of formazan. The formazan can be extracted from the column and measured spectrophotometrically. 3. The formation of formazan was found to be directly related to the number of phagocytes in blood. 4. Two patients with chronic granulomatous disease gave abnormal results, suggesting that the test procedure may be of value as a screening procedure for this disease. PMID:1106938

  8. Designing of promiscuous inhibitors against pancreatic cancer cell lines

    NASA Astrophysics Data System (ADS)

    Kumar, Rahul; Chaudhary, Kumardeep; Singla, Deepak; Gautam, Ankur; Raghava, Gajendra P. S.

    2014-04-01

    Pancreatic cancer remains the most devastating disease with worst prognosis. There is a pressing need to accelerate the drug discovery process to identify new effective drug candidates against pancreatic cancer. We have developed QSAR models for predicting promiscuous inhibitors using the pharmacological data. Our models achieved maximum Pearson correlation coefficient of 0.86, when evaluated on 10-fold cross-validation. Our models have also successfully validated the drug-to-oncogene relationship and further we used these models to screen FDA approved drugs and tested them in vitro. We have integrated these models in a webserver named as DiPCell, which will be useful for screening and designing novel promiscuous drug molecules. We have also identified the most and least effective drugs for pancreatic cancer cell lines. On the other side, we have identified resistant pancreatic cancer cell lines, which need investigative scanner on them to put light on resistant mechanism in pancreatic cancer.

  9. Designing of promiscuous inhibitors against pancreatic cancer cell lines

    PubMed Central

    Kumar, Rahul; Chaudhary, Kumardeep; Singla, Deepak; Gautam, Ankur; Raghava, Gajendra P. S.

    2014-01-01

    Pancreatic cancer remains the most devastating disease with worst prognosis. There is a pressing need to accelerate the drug discovery process to identify new effective drug candidates against pancreatic cancer. We have developed QSAR models for predicting promiscuous inhibitors using the pharmacological data. Our models achieved maximum Pearson correlation coefficient of 0.86, when evaluated on 10-fold cross-validation. Our models have also successfully validated the drug-to-oncogene relationship and further we used these models to screen FDA approved drugs and tested them in vitro. We have integrated these models in a webserver named as DiPCell, which will be useful for screening and designing novel promiscuous drug molecules. We have also identified the most and least effective drugs for pancreatic cancer cell lines. On the other side, we have identified resistant pancreatic cancer cell lines, which need investigative scanner on them to put light on resistant mechanism in pancreatic cancer. PMID:24728108

  10. Amylase Test

    MedlinePlus

    ... tests are sometimes used to monitor treatment of cancers involving the pancreas and after the removal of gallstones that have ... in people with pancreatic duct obstruction and pancreatic cancers . In ... cells in the pancreas. Decreased levels can also be due to kidney ...

  11. Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis.

    PubMed

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-04-01

    Upon hemolysis extracellular hemoglobin causes oxidative stress and cytotoxicity due to its peroxidase activity. Extracellular hemoglobin may release free hemin, which increases vascular permeability, leukocyte recruitment, and adhesion molecule expression. Pancreatitis-associated ascitic fluid is reddish and may contain extracellular hemoglobin. Our aim has been to determine the role of extracellular hemoglobin in the local and systemic inflammatory response during severe acute pancreatitis in rats. To this end we studied taurocholate-induced necrotizing pancreatitis in rats. First, extracellular hemoglobin in ascites and plasma was quantified and the hemolytic action of ascitic fluid was tested. Second, we assessed whether peritoneal lavage prevented the increase in extracellular hemoglobin in plasma during pancreatitis. Third, hemoglobin was purified from rat erythrocytes and administered intraperitoneally to assess the local and systemic effects of ascitic-associated extracellular hemoglobin during acute pancreatitis. Extracellular hemoglobin and hemin levels markedly increased in ascitic fluid and plasma during necrotizing pancreatitis. Peroxidase activity was very high in ascites. The peritoneal lavage abrogated the increase in extracellular hemoglobin in plasma. The administration of extracellular hemoglobin enhanced ascites; dramatically increased abdominal fat necrosis; upregulated tumor necrosis factor-α, interleukin-1β, and interleukin-6 gene expression; and decreased expression of interleukin-10 in abdominal adipose tissue during pancreatitis. Extracellular hemoglobin enhanced the gene expression and protein levels of vascular endothelial growth factor (VEGF) and other hypoxia-inducible factor-related genes in the lung. Extracellular hemoglobin also increased myeloperoxidase activity in the lung. In conclusion, extracellular hemoglobin contributes to the inflammatory response in severe acute pancreatitis through abdominal fat necrosis and inflammation

  12. Abnormal thyroid function tests in children on ethionamide treatment.

    PubMed

    Thee, S; Zöllner, E W; Willemse, M; Hesseling, A C; Magdorf, K; Schaaf, H S

    2011-09-01

    Ethionamide (ETH) treatment may cause hypothyroidism. Clinical data, serum thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels were retrospectively assessed in 137 children receiving anti-tuberculosis treatment including ETH. Abnormal thyroid function tests (TFTs) were recorded in 79 (58%) children: elevated serum TSH and suppressed fT4 (n = 30), isolated elevated serum TSH (n = 20), isolated low serum fT4 (n = 28) and isolated low TSH (n = 1). The risk for biochemical hypothyroidism was higher for children on regimens including para-aminosalicylic acid and in human immunodeficiency virus infected children. TFT abnormalities are frequent in children on ETH and are mainly due to primary hypothyroidism or euthyroid sick syndrome. PMID:21943844

  13. Lipoxin A4 Attenuates Cell Invasion by Inhibiting ROS/ERK/MMP Pathway in Pancreatic Cancer

    PubMed Central

    Zong, Liang; Li, Jiahui; Chen, Xin; Chen, Ke; Li, Wei; Li, Xuqi; Zhang, Lun; Duan, Wanxing; Lei, Jianjun; Xu, Qinhong; Shan, Tao; Ma, Qingyong; Sun, Hao

    2016-01-01

    Lipoxin A4 (LXA4), an endogenous arachidonic acid metabolite, was previously considered an anti-inflammatory lipid mediator. But it also has the potential to inhibit cancer progression. To explore the therapeutic effect of LXA4 in pancreatic cancer, we used Panc-1 cells to investigate the mechanism by which LXA4 can attenuate pancreatic cancer cell invasion. Our data showed that LXA4 significantly inhibited both cell invasion and the expression of matrix metalloproteinase- (MMP-) 9 and MMP-2. Further experiments implied that LXA4 decreased the levels of intracellular reactive oxygen species (ROS) and the activity of the extracellular signal regulated kinases (ERK) pathway to achieve similar outcome to ROS scavenger N-acetyl-l-cysteine (NAC). However, a decreased level of intracellular ROS was not observed in cells treated with the specific ERK pathway inhibitor FR180204. The blocking of either intracellular ROS or ERK pathway caused the downregulation of MMP-9 and MMP-2 expression. Furthermore, tests revealed that LXA4 inhibited MMP-9 and MMP-2 at the mRNA, protein, and functional levels. Finally, LXA4 dramatically limited the invasion of CoCl2-mimic hypoxic cells and abrogated intracellular ROS levels, ERK activity, and MMPs expression. These results suggest that LXA4 attenuates cell invasion in pancreatic cancer by suppressing the ROS/ERK/MMPs pathway, which may be beneficial for preventing the invasion of pancreatic cancer. PMID:26649143

  14. Isolated pancreatic aplasia due to a hypomorphic PTF1A mutation

    PubMed Central

    Flanagan, Sarah E.; de Franco, Elisa; Caswell, Richard; Hussain, Khalid; Mohamed, Sarar; Abdulrasoul, Majedah; Hattersley, Andrew T.; MacDonald, Raymond J.; Ellard, Sian

    2016-01-01

    Homozygous truncating mutations in the helix-loop-helix transcription factor PTF1A are a rare cause of pancreatic and cerebellar agenesis. The correlation of Ptf1a dosage with pancreatic phenotype in a mouse model suggested the possibility of finding hypomorphic PTF1A mutations in patients with pancreatic agenesis or neonatal diabetes but no cerebellar phenotype. Genome wide SNP typing in two siblings with neonatal diabetes from a consanguineous pedigree revealed a large shared homozygous region (31 Mb) spanning PTF1A. Sanger sequencing of PTF1A identified a novel missense mutation, p.P191T. Testing of 259 additional patients using a targeted next generation sequencing assay for 23 neonatal diabetes genes detected one additional proband and an affected sibling with the same homozygous mutation. All 4 cases were diagnosed with diabetes at birth and are insulin treated. Two of the 4 had exocrine pancreatic insufficiency requiring replacement but none of the affected individuals have neurodevelopmental delay. Transient transfection assays of the mutant protein demonstrated a 75% reduction in transactivation activity. This study shows that the functional severity of a homozygous mutation impacts on the severity of clinical features found in patients. PMID:27284104

  15. Isolated Pancreatic Aplasia Due to a Hypomorphic PTF1A Mutation.

    PubMed

    Houghton, Jayne A L; Swift, Galvin H; Shaw-Smith, Charles; Flanagan, Sarah E; de Franco, Elisa; Caswell, Richard; Hussain, Khalid; Mohamed, Sarar; Abdulrasoul, Majedah; Hattersley, Andrew T; MacDonald, Raymond J; Ellard, Sian

    2016-09-01

    Homozygous truncating mutations in the helix-loop-helix transcription factor PTF1A are a rare cause of pancreatic and cerebellar agenesis. The correlation of Ptf1a dosage with pancreatic phenotype in a mouse model suggested the possibility of finding hypomorphic PTF1A mutations in patients with pancreatic agenesis or neonatal diabetes but no cerebellar phenotype. Genome-wide single nucleotide polymorphism typing in two siblings with neonatal diabetes from a consanguineous pedigree revealed a large shared homozygous region (31 Mb) spanning PTF1A Sanger sequencing of PTF1A identified a novel missense mutation, p.P191T. Testing of 259 additional patients using a targeted next-generation sequencing assay for 23 neonatal diabetes genes detected one additional proband and an affected sibling with the same homozygous mutation. All four patients were diagnosed with diabetes at birth and were treated with insulin. Two of the four patients had exocrine pancreatic insufficiency requiring replacement therapy but none of the affected individuals had neurodevelopmental delay. Transient transfection assays of the mutant protein demonstrated a 75% reduction in transactivation activity. This study shows that the functional severity of a homozygous mutation impacts the severity of clinical features found in patients. PMID:27284104

  16. Unraveling pancreatic islet biology by quantitative proteomics

    SciTech Connect

    Zhou, Jianying; Dann, Geoffrey P.; Liew, Chong W.; Smith, Richard D.; Kulkarni, Rohit N.; Qian, Weijun

    2011-08-01

    The pancreatic islets of Langerhans play a critical role in maintaining blood glucose homeostasis by secreting insulin and several other important peptide hormones. Impaired insulin secretion due to islet dysfunction is linked to the pathogenesis underlying both Type 1 and Type 2 diabetes. Over the past 5 years, emerging proteomic technologies have been applied to dissect the signaling pathways that regulate islet functions and gain an understanding of the mechanisms of islet dysfunction relevant to diabetes. Herein, we briefly review some of the recent quantitative proteomic studies involving pancreatic islets geared towards gaining a better understanding of islet biology relevant to metabolic diseases.

  17. Pancreatic injury in patients with septic shock: A literature review

    PubMed Central

    Chaari, Anis; Abdel Hakim, Karim; Bousselmi, Kamel; Etman, Mahmoud; El Bahr, Mohamed; El Saka, Ahmed; Hamza, Eman; Ismail, Mohamed; Khalil, Elsayed Mahmoud; Kauts, Vipin; Casey, William Francis

    2016-01-01

    Sepsis and septic shock are life threatening condition associated with high mortality rate in critically-ill patients. This high mortality is mainly related to the inadequacy between oxygen delivery and cellular demand leading to the onset of multiorgan dysfunction. Whether this multiorgan failure affect the pancreas is not fully investigated. In fact, pancreatic injury may occur because of ischemia, overwhelming inflammatory response, oxidative stress, cellular apoptosis and/or metabolic derangement. Increased serum amylase and/or lipase levels are common in patients with septic shock. However, imaging test rarely reveal significant pancreatic damage. Whether pancreatic dysfunction does affect the prognosis of patients with septic shock or not is still a matter of debate. In fact, only few studies with limited sample size assessed the clinical relevance of the pancreatic injury in this group of patients. In this review, we aimed to describe the epidemiology and the physiopathology of pancreatic injury in septic shock patients, to clarify whether it requires specific management and to assess its prognostic value. Our main finding is that pancreatic injury does not significantly affect the outcome in septic shock patients. Hence, increased serum pancreatic enzymes without clinical features of acute pancreatitis do not require further imaging investigations and specific therapeutic intervention. PMID:27559431

  18. Pancreatic injury in patients with septic shock: A literature review.

    PubMed

    Chaari, Anis; Abdel Hakim, Karim; Bousselmi, Kamel; Etman, Mahmoud; El Bahr, Mohamed; El Saka, Ahmed; Hamza, Eman; Ismail, Mohamed; Khalil, Elsayed Mahmoud; Kauts, Vipin; Casey, William Francis

    2016-07-15

    Sepsis and septic shock are life threatening condition associated with high mortality rate in critically-ill patients. This high mortality is mainly related to the inadequacy between oxygen delivery and cellular demand leading to the onset of multiorgan dysfunction. Whether this multiorgan failure affect the pancreas is not fully investigated. In fact, pancreatic injury may occur because of ischemia, overwhelming inflammatory response, oxidative stress, cellular apoptosis and/or metabolic derangement. Increased serum amylase and/or lipase levels are common in patients with septic shock. However, imaging test rarely reveal significant pancreatic damage. Whether pancreatic dysfunction does affect the prognosis of patients with septic shock or not is still a matter of debate. In fact, only few studies with limited sample size assessed the clinical relevance of the pancreatic injury in this group of patients. In this review, we aimed to describe the epidemiology and the physiopathology of pancreatic injury in septic shock patients, to clarify whether it requires specific management and to assess its prognostic value. Our main finding is that pancreatic injury does not significantly affect the outcome in septic shock patients. Hence, increased serum pancreatic enzymes without clinical features of acute pancreatitis do not require further imaging investigations and specific therapeutic intervention. PMID:27559431

  19. A NEW CLINICAL MUSCLE FUNCTION TEST FOR ASSESSMENT OF HIP EXTERNAL ROTATION STRENGTH: AUGUSTSSON STRENGTH TEST

    PubMed Central

    2016-01-01

    ABSTRACT Introduction Dynamic clinical tests of hip strength applicable on patients, non–athletes and athletes alike, are lacking. The aim of this study was therefore to develop and evaluate the reliability of a dynamic muscle function test of hip external rotation strength, using a novel device. A second aim was to determine if gender differences exist in absolute and relative hip strength using the new test. Methods Fifty–three healthy sport science students (34 women and 19 men) were tested for hip external rotation strength using a device that consisted of a strap connected in series with an elastic resistance band loop, and a measuring tape connected in parallel with the elastic resistance band. The test was carried out with the subject side lying, positioned in 45 ° of hip flexion and the knees flexed to 90 ° with the device firmly fastened proximally across the knees. The subject then exerted maximal concentric hip external rotation force against the device thereby extending the elastic resistance band. The displacement achieved by the subject was documented by the tape measure and the corresponding force production was calculated. Both right and left hip strength was measured. Fifteen of the subjects were tested on repeated occasions to evaluate test–retest reliability. Results No significant test–retest differences were observed. Intra–class correlation coefficients ranged 0.93–0.94 and coefficients of variation 2.76–4.60%. In absolute values, men were significantly stronger in hip external rotation than women (right side 13.2 vs 11.0 kg, p = 0.001, left side 13.2 vs 11.5 kg, p = 0.002). There were no significant differences in hip external rotation strength normalized for body weight (BW) between men and women (right side 0.17 kg/BW vs 0.17 kg/BW, p = 0.675, left side 0.17 kg/BW vs 0.18 kg/BW, p = 0.156). Conclusions The new muscle function test showed high reliability and thus could be useful for measuring dynamic hip

  20. [Pancreatic neuroendocrine neoplasms].

    PubMed

    Beiderwellen, K; Sabet, A; Lauenstein, T C; Lahner, H; Poeppel, T D

    2016-04-01

    Pancreatic neuroendocrine neoplasms (NEN) account for 1-2% of all pancreatic neoplasms and represent a rare differential diagnosis. While some pancreatic NEN are hormonally active and exhibit endocrine activity associated with characteristic symptoms, the majority are hormonally inactive. Imaging techniques such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) or as combined PET/CT play a crucial role in the initial diagnosis, therapy planning and control. Endoscopic ultrasound (EUS) and multiphase CT represent the reference methods for localization of the primary pancreatic tumor. Particularly in the evaluation of small liver lesions MRI is the method of choice. Somatostatin receptor scintigraphy and somatostatin receptor PET/CT are of particular value for whole body staging and special aspects of further therapy planning. PMID:27003413

  1. Surgery for Pancreatic Cancer

    MedlinePlus

    ... the abdomen. The surgeon can look at the pancreas and other organs for tumors and take biopsy ... pancreatic cancers appear to be confined to the pancreas at the time they are found. Even then, ...

  2. Pancreatic Islet Transplantation

    MedlinePlus

    ... of immunosuppressive medications?" [ Top ] Collaborative Islet Transplant Registry Data In its 2010 annual report, 1 the Collaborative Islet Transplant Registry presented data on 571 patients who received pancreatic islet allo- ...

  3. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... sudden inflammation of the pancreas manifested clinically by abdominal pain, nausea and dehydration that is usually self-limiting ... room for evaluation should they develop any abnormal abdominal pain symptoms. Conclusions While a rare event, acute pancreatitis ...

  4. Acute Pancreatitis in Children

    MedlinePlus

    ... are the symptoms of pancreatitis? Common symptoms include abdominal pain, nausea, and vomiting. However, not every patient with ... help the pancreas to recover. Patients who have abdominal pain can be treated with pain medications. Some patients ...

  5. What Is Pancreatic Cancer?

    MedlinePlus

    ... very important to distinguish between exocrine and endocrine cancers of the pancreas. They have distinct risk factors and causes, have ... are by far the most common type of pancreas cancer. If you are told you have pancreatic cancer, ...

  6. Pancreatic Islet Transplantation

    MedlinePlus

    ... allo-transplantation?" For each pancreatic islet allo-transplant infusion, researchers use specialized enzymes to remove islets from ... in a lab. Transplant patients typically receive two infusions with an average of 400,000 to 500, ...

  7. Design and functional tests of variable SFQ pulse number multiplier

    NASA Astrophysics Data System (ADS)

    Saito, J.; Tanaka, T.; Moriya, M.; Kobayashi, T.; Mizugaki, Y.; Maezawa, M.

    2011-11-01

    For establishing a new generation of ac voltage standards, digital-to-analog converters (DACs) based on rapid single flux quantum (RSFQ) technology, which enable synthesis of arbitrary waveforms with fundamental accuracy, are developed. An RSFQ-DAC consists of three main subsystems: a pulse-number multiplier (PNM), a pulse distributor (PD) and voltage multipliers (VMs). Conventional RSFQ-DACs generate arbitrary voltages by switching a binary array of the VM cells. In this paper, we propose a Variable-PNM for a new RSFQ-DAC based on frequency modulation. The output voltage is determined by the multiplication factor m of the Variable-PNM that consists of a ring oscillator, an n-bit counter and a decoder. We designed a 2-bit Variable-PNM using the CONNECT cell library. The circuit was fabricated using the ISTEC Nb standard process (STP2). We have confirmed the correct functionalities for 2-, 4-, 6- and 8-fold multiplication in functional testing at low speed.

  8. Above-Level Test Item Functioning across Examinee Age Groups

    ERIC Educational Resources Information Center

    Warne, Russell T.; Doty, Kristine J.; Malbica, Anne Marie; Angeles, Victor R.; Innes, Scott; Hall, Jared; Masterson-Nixon, Kelli

    2016-01-01

    "Above-level testing" (also called "above-grade testing," "out-of-level testing," and "off-level testing") is the practice of administering to a child a test that is designed for an examinee population that is older or in a more advanced grade. Above-level testing is frequently used to help educators design…