Science.gov

Sample records for pancreatic function test

  1. Clinical usefulness of dual-label Schilling test for pancreatic exocrine function

    SciTech Connect

    Chen, W.L.; Morishita, R.; Eguchi, T.; Kawai, T.; Sakai, M.; Tateishi, H.; Uchino, H.

    1989-05-01

    The usefulness of the pancreatic dual-label Schilling test as an indirect test of pancreatic exocrine function was evaluated. This dual-label Schilling test was based on the difference of absorption for (58Co)cobalamin bound to hog R protein and (57Co)cobalamin bound to intrinsic factor. In this study, the test was performed in 7 normal subjects, 5 patients with pancreatectomy, 12 patients with chronic pancreatitis, 10 patients with suspicion of chronic pancreatitis, and 13 patients without chronic pancreatitis. The normal lower limit (mean -2 SD) of excretion ratio for (58Co)/(57Co) in 24-h urine was 0.68. Of the 26 patients on whom endoscopic retrograde pancreatography was performed, none of the 9 patients with normal pancreatogram, 4 of the 9 patients with mild to moderate pancreatitic changes in pancreatogram, and 7 of the 8 patients with advanced pancreatitic changes in pancreatogram showed a positive value lower than the ratio of 0.68 in this test. In 28 patients examined with the direct test of pancreatic secretory capacity, 2 of the 13 patients with normal function, 6 of the 9 patients with mild dysfunction, and 5 of the 6 patients with definite dysfunction were positive in this test. The results of the pancreatic dual-label Schilling test significantly correlated with those of a direct test of pancreatic secretory capacity and the findings of pancreatitic changes in pancreatogram (p less than 0.01, chi 2 test). The ratio for (58Co)/(57Co) correlated (r = 0.73) with the maximal bicarbonate concentration in duodenal juice of the direct test of pancreatic secretory capacity. The impairment of bicarbonate output by the pancreas may adversely affect the transfer of cobalamin from R protein to intrinsic factor.

  2. A Test of Pancreatic Function in Man Based on the Analysis of Duodenal Contents after Administration of Secretin and Pancreozymin

    PubMed Central

    Burton, P.; Evans, D. G.; Harper, A. A.; Howat, Henry T.; Oleesky, S.; Scott, J. E.; Varley, H.

    1960-01-01

    Pancreozymin in man as in animals appears to act as a specific enzyme stimulant. The preparations of pancreozymin used in these experiments also contain cholecystokinin, which causes the gall bladder to contract, and a smooth muscle stimulant, possibly substance P. The duodenal contents obtained in response to a standard dose of secretin and pancreozymin have been collected quantitatively in man and the volume and amount of bicarbonate, amylase, trypsin, and lipase measured in order to study pancreatic function. The results of 105 tests undertaken on a normal group, in pancreatic and biliary disease, and in non-pancreatic steatorrhoea have been analysed. In localized pancreatic lesions and after recovery from acute pancreatitis, normal function is often retained. Mild functional impairment may be demonstrated only by a poor enzyme output in the post-pancreozymin fractions, while at a later stage bicarbonate output is affected and finally the volume of the duodenal contents is reduced. The secretin-pancreozymin test is most valuable, therefore, in the more chronic and advanced forms of pancreatic disease in which it gives a good assessment of residual pancreatic function. In diagnosis care must be taken in interpreting a functional test in terms of anatomical pathology. The test has proved useful not only in diagnosis but also as a guide to treatment and an index of prognosis. PMID:13806339

  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.

  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.

  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. Effect of octreotide acetate on pancreatic exocrine function.

    PubMed

    Williams, S T; Woltering, E A; O'Dorisio, T M; Fletcher, W S

    1989-05-01

    Somatostatin and its analogs have been shown to inhibit both pancreatic endocrine and exocrine function. We hypothesized that octreotide acetate (Sandostatin), a somatostatin analog, decreases the pancreatic flow rate through a peptide-mediated mechanism and alters pancreatic fluid composition by inhibiting carbonic anhydrase action and circulating peptide levels. To test this hypothesis, we collected pancreatic fluid from six patients (four with pancreatic fistulas and two with pancreatic drains after pancreatic resection). Pancreatic fluid volume and chloride, sodium, potassium, amylase, lipase, and bicarbonate levels were measured before and after octreotide acetate therapy. Octreotide acetate reduced pancreatic fluid output by a mean of 75 percent (p less than 0.05), increased chloride concentration by 21 percent (p less than 0.05), and reduced bicarbonate content by 45 percent (p less than 0.05). Sodium levels were unchanged, but the potassium concentration was increased by 14 percent (p less than 0.05). Total amylase and lipase production per 24 hours was decreased by 63 percent and 27 percent, respectively (differences not significant). Somatostatin may be useful in the treatment of established pancreatic fistulas and may be a useful prophylactic tool to prevent postoperative fistula formation.

  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. Exocrine pancreatic function in children with Alagille syndrome

    PubMed Central

    Gliwicz, Dorota; Jankowska, Irena; Wierzbicka, Aldona; Miśkiewicz-Chotnicka, Anna; Lisowska, Aleksandra; Walkowiak, Jarosław

    2016-01-01

    Alagille syndrome (AGS) is often associated with symptoms of maldigestion, such as steatorrhea, hypotrophy and growth retardation. Exocrine pancreatic insufficiency was proposed as the underlying cause. We aimed to assess the exocrine pancreatic function with the use of different methods in AGS patients. Concentrations of fecal elastase-1 (FE1) and fecal lipase (FL) activities were measured in 33 children with AGS. The C-mixed triglyceride breath test (MTBT) in a subgroup comprising 15 patients. In all patients studied, FE1 concentrations and FL activities were normal. Abnormal MTBT results were documented in 4 (26.7%) patients. The FE1 and FL levels in MTBT-positive and MTBT-negative children did not differ. The results of this research do not confirm the presence of exocrine pancreatic dysfunction in AGS patients. Routine screening for exocrine pancreatic insufficiency of this group of patients is not necessary. PMID:27748459

  10. Chronic pancreatitis.

    PubMed

    Chari, S T; DiMagno, E P

    2000-09-01

    In the past year, there has been at least one important clinical paper that sheds light on the character and natural history of painful chronic pancreatitis, which has important clinical implications. In addition, several novel mutations have been described in the cationic trypsinogen gene in patients with hereditary pancreatitis. The mechanism by which these mutations cause pancreatic disease remains speculative. The diagnosis of early chronic pancreatitis is controversial. A novel noninvasive pancreatic function test (measurement of postprandial APOB-48) was reported but is unlikely to be a sensitive test of pancreatic function. Pancreatic fibrosis is frequently seen in alcoholics without chronic pancreatitis, and this makes it difficult to interpret the findings on endoscopic ultrasonogram. Recent studies highlight the difficulty in abolishing pancreatic steatorrhea. Recently fibrosing colonopathy in adult patients has been reported. Extracorporeal shockwave lithotripsy combined with endoscopic therapy failed to benefit patients with calcific chronic pancreatitis.

  11. Effects of ORP150 on appearance and function of pancreatic beta cells following acute necrotizing pancreatitis.

    PubMed

    Deng, Wen-Hong; Chen, Chen; Wang, Wei-Xing; Yu, Jia; Li, Jin-You; Liu, Lei

    2011-06-15

    Pancreatic beta cells produce and release insulin, which decreases the blood glucose level. Endoplasmic reticulum stress caused pancreatic beta cell dysfunction and death in acute necrotizing pancreatitis (ANP). The 150kD oxygen-regulated protein (ORP150) took part in the process of endoplasmic reticulum stress. This study investigated the effect of ORP150 on appearance and function of pancreatic beta cells in ANP. Acute necrotizing pancreatitis relied on retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. The severity of ANP was estimated by serum amylase, secretory phospholipase A(2,) and pancreatic histopathology. The changes in appearance and function of pancreatic beta cells were detected by light and electron microscopy and the levels of serum glucose, insulin, and C-peptide. ORP150 expression was studied using western blot and immunohistochemisty assay. The expression of ORP150 mainly appeared on pancreatic beta cells and decreased gradually during the pathogenesis of ANP. The results of light and electron microscopy indicated pancreatic beta cell dysfunction and death, concomitant with elevation of serum glucose, insulin, and C-peptide in ANP. These results imply a probable role of ORP150 in the changes in appearance and function of pancreatic beta cells following acute necrotizing pancreatitis, through the pathway of endoplasmic reticulum stress.

  12. 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.

  13. New DNA Methylation Markers for Pancreatic Cancer: Discovery, Tissue Validation, and Pilot Testing in Pancreatic Juice

    PubMed Central

    Kisiel, John B.; Raimondo, Massimo; Taylor, William R.; Yab, Tracy C.; Mahoney, Douglas W.; Sun, Zhifu; Middha, Sumit; Baheti, Saurabh; Zou, Hongzhi; Smyrk, Thomas C.; Boardman, Lisa A.; Petersen, Gloria M.; Ahlquist, David A.

    2015-01-01

    Purpose Discriminant markers for pancreatic cancer detection are needed. We sought to identify and validate methylated DNA markers for pancreatic cancer using next-generation sequencing unbiased by known targets. Experimental Design At a referral center, we conducted four sequential case-control studies: discovery, technical validation, biological validation, and clinical piloting. Candidate markers were identified using variance inflated logistic regression on reduced-representation bisulfite DNA sequencing results from matched pancreatic cancers, benign pancreas, and normal colon tissues. Markers were validated technically on replicate discovery study DNA and biologically on independent, matched, blinded tissues by methylation specific PCR. Clinical testing of 6 methylation candidates and mutant KRAS was performed on secretin-stimulated pancreatic juice samples from 61 pancreatic cancer patients, 22 with chronic pancreatitis and 19 with normal pancreas on endoscopic ultrasound. Areas under receiver operating characteristics curves (AUC) for markers were calculated. Results Sequencing identified >500 differentially hyper-methylated regions. On independent tissues, AUC on 19 selected markers ranged between 0.73 – 0.97. Pancreatic juice AUC values for CD1D, KCNK12, CLEC11A, NDRG4, IKZF1, PKRCB and KRAS were 0.92*, 0.88, 0.85, 0.85, 0.84, 0.83 and 0.75, respectively, for pancreatic cancer compared to normal pancreas and 0.92*, 0.73, 0.76, 0.85*, 0.73, 0.77 and 0.62 for pancreatic cancer compared to chronic pancreatitis (*p=0.001 vs KRAS). Conclusion We identified and validated novel DNA methylation markers strongly associated with pancreatic cancer. On pilot testing in pancreatic juice, best markers (especially CD1D) highly discriminated pancreatic cases from controls. PMID:26023084

  14. Pancreatic exocrine and endocrine function after subtotal pancreatectomy for nesidioblastosis.

    PubMed

    Dunger, D B; Burns, C; Ghale, G K; Muller, D P; Spitz, L; Grant, D B

    1988-02-01

    Pancreatic exocrine and endocrine function was assessed in seven patients 1 to 2 years after 95% pancreatectomy (group A) and three patients 9 to 11 years after 75% pancreatectomy (group B). In all cases surgery was undertaken for the treatment of hyperinsulinism and the histologic diagnosis was nesidioblastosis. The activities of pancreatic enzymes and bicarbonate concentrations were generally normal in group B, but were reduced in approximately half the children in group A. One child in group A had significant exocrine failure and poor weight gain. Blood glucose levels and fasting insulin levels were normal during a standard glucose tolerance test in all of the group B patients. One had a low fasting blood glucose level. In the group A patients three had low fasting glucose levels and one a frankly diabetic glucose tolerance test. C peptide and insulin levels were comparable but inappropriate insulin levels were noted in one patient, suggesting that the control of glucose-stimulated insulin release may remain abnormal. The results suggest that pancreatic function is not seriously impaired in the majority of patients 1 to 2 years after 95% pancreatectomy and that it is comparable to that noted in 75% pancreatectomy patients followed over a longer period of time.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. Immune cell functions in pancreatic cancer.

    PubMed

    Plate, J M; Harris, J E

    2000-01-01

    Pancreatic cancer kills nearly 29,000 people in the United States annually-as many people as are diagnosed with the disease. Chemotherapeutic treatment is ineffective in halting progression of the disease. Yet, specific immunity to pancreatic tumor cells in subjects with pancreatic cancer has been demonstrated repeatedly during the last 24 years. Attempts to expand and enhance tumor-specific immunity with biotherapy, however, have not met with success. The question remains, "Why can't specific immunity regulate pancreatic cancer growth?" The idea that tumor cells have evolved protective mechanisms against immunity was raised years ago and has recently been revisited by a number of research laboratories. In pancreatic cancer, soluble factors produced by and for the protection of the tumor environment have been detected and are often distributed to the victim's circulatory system where they may effect a more generalized immunosuppression. Yet the nature of these soluble factors remains controversial, since some also serve as tumor antigens that are recognized by the same T cells that may become inactivated by them. Unless the problem of tumor-derived immunosuppressive products is addressed directly through basic and translational research studies, successful biotherapeutic treatment for pancreatic cancer may not be forthcoming.

  2. Pancreatic stellate cells--multi-functional cells in the pancreas.

    PubMed

    Masamune, Atsushi; Shimosegawa, Tooru

    2013-01-01

    There is accumulating evidence that activated pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis in chronic pancreatitis and pancreatic cancer. In addition, we have seen great progress in our understanding of the cell biology of PSCs and the interactions between PSCs and other cell types in the pancreas. In response to pancreatic injury or inflammation, quiescent PSCs are activated to myofibroblast-like cells. Recent studies have shown that the activation of intracellular signaling pathways such as mitogen-activated protein kinases plays a role in the activation of PSCs. microRNAs might also play a role, because the microRNA expression profiles are dramatically altered in the process of activation. In addition to producing extracellular matrix components such as type I collagen, PSCs have a wide variety of cell functions related to local immunity, inflammation, angiogenesis, and exocrine and endocrine functions in the pancreas. From this point of view, the interactions between PSCs and other cell types such as pancreatic exocrine cells, endocrine cells, and cancer cells have attracted increasing attention of researchers. PSCs might regulate exocrine functions in the pancreas through the cholecystokinin-induced release of acetylcholine. PSCs induce apoptosis and decrease insulin expression in β-cells, suggesting a novel mechanism of diabetes in diseased pancreas. PSCs promote the progression of pancreatic cancer by multiple mechanisms. Recent studies have shown that PSCs induce epithelial-mesenchymal transition and enhance the stem-cell like features of pancreatic cancer cells. In conclusion, PSCs should now be recognized as not only profibrogenic cells but as multi-functional cells in the pancreas.

  3. Pancreatitis.

    PubMed

    Mitchell, R M S; Byrne, M F; Baillie, J

    2003-04-26

    In the past decade, our understanding of the genetic basis, pathogenesis, and natural history of pancreatitis has grown strikingly. In severe acute pancreatitis, intensive medical support and non-surgical intervention for complications keeps patients alive; surgical drainage (necrosectomy) is reserved for patients with infected necrosis for whom supportive measures have failed. Enteral feeding has largely replaced the parenteral route; controversy remains with respect to use of prophylactic antibiotics. Although gene therapy for chronic pancreatitis is years away, our understanding of the roles of gene mutations in hereditary and sporadic pancreatitis offers tantalising clues about the disorder's pathogenesis. The division between acute and chronic pancreatitis has always been blurred: now, genetics of the disorder suggest a continuous range of disease rather than two separate entities. With recognition of pancreatic intraepithelial neoplasia, we see that chronic pancreatitis is a premalignant disorder in some patients. Magnetic resonance cholangiopancreatography and endoscopic ultrasound are destined to replace endoscopic retrograde cholangiopancreatography for many diagnostic indications in pancreatic disease.

  4. 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 ...

  5. 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

  6. A red-shifted photochromic sulfonylurea for the remote control of pancreatic beta cell function.

    PubMed

    Broichhagen, J; Frank, J A; Johnston, N R; Mitchell, R K; Šmid, K; Marchetti, P; Bugliani, M; Rutter, G A; Trauner, D; Hodson, D J

    2015-04-01

    Azobenzene photoresponsive elements can be installed on sulfonylureas, yielding optical control over pancreatic beta cell function and insulin release. An obstacle to such photopharmacological approaches remains the use of ultraviolet-blue illumination. Herein, we synthesize and test a novel yellow light-activated sulfonylurea based on a heterocyclic azobenzene bearing a push-pull system. PMID:25744824

  7. 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

  8. Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor.

    PubMed

    Valetti, Sabrina; Maione, Federica; Mura, Simona; Stella, Barbara; Desmaële, Didier; Noiray, Magali; Vergnaud, Juliette; Vauthier, Christine; Cattel, Luigi; Giraudo, Enrico; Couvreur, Patrick

    2014-10-28

    Chemotherapy for pancreatic cancer is hampered by the tumor's physio-pathological complexity. Here we show a targeted nanomedicine using a new ligand, the CKAAKN peptide, which had been identified by phage display, as an efficient homing device within the pancreatic pathological microenvironment. Taking advantage of the squalenoylation platform, the CKAAKN peptide was conjugated to squalene (SQCKAAKN) and then co-nanoprecipitated with the squalenoyl prodrug of gemcitabine (SQdFdC) giving near monodisperse nanoparticles (NPs) for safe intravenous injection. By interacting with a novel target pathway, the Wnt-2, the CKAAKN functionalization enabled nanoparticles: (i) to specifically interact with both tumor cells and angiogenic vessels and (ii) to simultaneously promote pericyte coverage, thus leading to the normalization of the vasculature likely improving the tumor accessibility for therapy. All together, this approach represents a unique targeted nanoparticle design with remarkable selectivity towards pancreatic cancer and multiple mechanisms of action.

  9. Exocrine pancreatic function in man after treatment with oxytetracycline and chloramphenicol.

    PubMed

    Fleischer, K

    1976-01-01

    The exocrine pancreatic function was studied in humans by performing a secretin-cholecystokinin test before and after treatment with oxytetracycline or chloramphenicol. In the oxytetracycline-treated patients there was a depression of the amylase and lipase outputs in the duodenal secretion, chymotrypsin decreasing only slightly. After treatment with the two antibiotics the calcium secretion was reduced. The other parameters measured in the duodenal secretion remained essentially unchanged. The enzyme dissociation observed in the present studies is considered to reflect the onset of pancreatic dysfunction due to antibiotic administration. As in the previous animal onset of pancreatic dysfunction due to antibiotic administration. As in the previous animal experiments, the suggested explanation for the changes in enzyme secretion is an inhibition of protein synthesis in the exocrine pancreas due to oxytetracycline and chloramphenicol. PMID:950076

  10. 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

  11. 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. ...

  12. Practical Interpretation and Application of Exocrine Pancreatic Testing in Small Animals.

    PubMed

    Mansfield, Caroline

    2015-09-01

    The pancreas remains a difficult organ to evaluate using laboratory methods alone. No single laboratory test is diagnostic of pancreatitis (chronic or acute) without other diagnostic modalities concurring with the diagnosis or ruling out other diseases. The diagnosis of pancreatitis is particularly difficult in cats, and pancreatitis often occurs with other diseases. The use of pancreatic cytology may be useful in diagnosing both inflammation and neoplasia. Exocrine pancreatic insufficiency (EPI) can be relatively easily diagnosed when clinically manifested by the measurement of trypsinlike immunoreactivity. Diagnosis is more difficult when EPI is subclinical.

  13. [The function of the hydrokinetic and ekbolic pancreas after acute pancreatitis].

    PubMed

    Tympner, F; Domschke, W; Rösch, W; Koch, H; Demling, L

    1976-11-01

    Thirteen patients were investigated 3-4 weeks (I. examination) and 3-5 months (II. examination) after the ceasing of the signs symptoms of an acute pancreatitis concerning their hydrokinetic and ekbolic pancreas-functions. In addition, the pancreatic ducts were demonstrated by ERCP. Reduction of the secretion were shown in 31% at the I. examination and in 23% at the II. examination. There were significant differences in the outputs of bicarbonate, trypsine and chymotrypsine compared to healthy test persons at the I. examination. At the II. examination, however, no significant differences could be observed compared to healthy test persons. The exocrine function of the pancreas was getting worse during the interval between the I. and II. examination in 2 cases but it became normal in 5 cases. Pathological alterations at the pancreativ-duct-system were not demonstrable shown at all.

  14. [The function of the hydrokinetic and ekbolic pancreas after acute pancreatitis].

    PubMed

    Tympner, F; Domschke, W; Rösch, W; Koch, H; Demling, L

    1976-11-01

    Thirteen patients were investigated 3-4 weeks (I. examination) and 3-5 months (II. examination) after the ceasing of the signs symptoms of an acute pancreatitis concerning their hydrokinetic and ekbolic pancreas-functions. In addition, the pancreatic ducts were demonstrated by ERCP. Reduction of the secretion were shown in 31% at the I. examination and in 23% at the II. examination. There were significant differences in the outputs of bicarbonate, trypsine and chymotrypsine compared to healthy test persons at the I. examination. At the II. examination, however, no significant differences could be observed compared to healthy test persons. The exocrine function of the pancreas was getting worse during the interval between the I. and II. examination in 2 cases but it became normal in 5 cases. Pathological alterations at the pancreativ-duct-system were not demonstrable shown at all. PMID:1007339

  15. 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, ...

  16. 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

  17. 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 ...

  18. 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

  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. 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

  1. [The clinical application of 13C-breath tests in pancreatic diseases].

    PubMed

    Cherniavskiĭ, V V

    2014-11-01

    Maldigestion persists in most patients with chronic pancreatitis (GP). 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 and 13C-corn starch breath tests as a tools for exocrine pancreatic insufficiency diagnosis, for evaluating fat and starch malabsorbtion in CP patients. 135 patients were included in the investigation. It has been shown, that 13C-breath tests could be useful tools in clinical practice for CP diagnosis. They are well correlate with fecal elastase-1 level, has high sensitivity and specificity for diagnosis of lipase and amylase deficiency. Tests make it possible to choose the initial pancreatic enzyme dosage and are beneficial during the treatment for pancreatic enzyme dose correction.

  2. 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.

  3. A novel screening test for detecting graft thrombosis after pancreatic transplantation using contrast-enhanced ultrasonography with sonazoid.

    PubMed

    Ito, T; Kenmochi, T; Nishikawa, T; Maruyama, M; Kusaka, M; Sasaki, H; Asano, T; Matsubara, H; Hoshinaga, K

    2014-01-01

    Pancreatic graft thrombosis is the primary cause of nonimmunologic graft loss, with an incidence ranging from 5% to 15%. Therefore, developing a screening test to detect graft thrombosis after pancreatic transplantation is important. We created a screening test to assess graft thrombosis after pancreatic transplantation using contrast-enhanced ultrasonography (CEUS) with Sonazoid in addition to Doppler ultrasonography. A total of seven patients were examined using CEUS after undergoing pancreatic transplantation. All patients were observed to have a clear blood flow from the horizontal region to the peripheral region of the splenic vein in the pancreatic graft, and only one of the seven patients exhibited a blood flow in the horizontal portion of the splenic vein on Doppler ultrasonography performed immediately after pancreatic transplantation. Results from CEUS with Sonazoid showed the blood flow in the splenic vein and parenchyma of the pancreatic graft in detail, despite the slow and lateral blood flow in the splenic vein of the pancreatic graft immediately after transplantation.

  4. 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

  5. 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 ...

  6. Effect of octreotide acetate on pancreatic exocrine and endocrine functions after pancreatoduodenal resection.

    PubMed

    Petrin, P; Antoniutti, M; Zaramella, D; Da Lio, C; Basso, D; Plebani, M; Panozzo, M P; Costantino, V; Pedrazzoli, S

    1995-01-01

    In view of forecasting the effect of octreotide acetate (Sandostatin) in preventing fistula formation after pancreatic surgery, 9 patients, who had pancreatoduodenectomy 8-12 days before, underwent a 2-day study. The first day, by means of a catheter located in the jejunal loop separately anastomosed to the pancreatic remnant, basal and after secretin stimulation pancreatic secretion was evaluated. During the 2nd day the possible inhibitory effect of octreotide on basal and stimulated secretion was investigated. Under the experimental conditions of the study Sandostatin showed little effect on the water and bicarbonate increase as stimulated by secretin. A greater hormone inhibitory effect on amylase production and pancreatic endocrine function was seen. On the basis of these results the use of Sandostatin can hardly be seen as useful in preventing fistula formation after pancreatic resection.

  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. In the absence of nutrients, pancreatic-biliary secretions in the jejunum do not exert feedback control of human pancreatic or gastric function.

    PubMed

    Krawisz, B R; Miller, L J; DiMagno, E P; Go, V L

    1980-01-01

    Feedback inhibition of basal pancreatic enzyme secretion by luminal pancreatic enzymes appears to be an important regulator of pancreatic secretion in some laboratory animals. To determine whether pancreatic enzymes in the jejunum influence pancreatic or gastric functions in healthy man, we intubated six subjects with a gastric sump tube and a four-lumen duodenal tube which provided (1) a duodenal perfusion site, (2) a duodenal aspiration site, (3) an inflatable balloon immediately distal to the aspiration site, and (4) a jejunal perfusion site immediately beyond the balloon. In this way, the gastroduodenal segment could be functionally separated from the remainder of the intestine. The jejunum was exposed to normal saline, active pancreatic-biliary secretions, or pancreatic-biliary secretions in which the enzymes had been inactivated by heat. Ten minutes after initiation of each jejunal perfusion, normal saline was instilled into the stomach. No differences in trypsin secretion, gastric acid secretion, or gastric emptying occurred with the different jejunal perfusates. We therefore conclude that normal man, in the absence of intraluminal nutrients, does not exhibit a jejunal pancreatic enzyme-dependent feedback control mechanism for pancreatic enzyme or gastric secretion. However, our study does not exclude the possibility of a duodenal feedback regulatory mechanism.

  9. 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

  10. 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.

  11. 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

  12. Pulmonary function tests

    MedlinePlus

    ... measured to estimate the lung volume. To measure diffusion capacity , you breathe a harmless gas, called a ... on your report after pulmonary function tests include: Diffusion capacity to carbon monoxide (DLCO) Expiratory reserve volume ( ...

  13. Functional Characterization of HCN Channels in Rat Pancreatic β Cells

    PubMed Central

    Zhang, Yi; Liu, Yunfeng; Qu, Jihong; Hardy, Alexandre; Zhang, Nina; Diao, Jingyu; Strijbos, Paul J.; Tsushima, Robert; Robinson, Richard B.; Gaisano, Herbert Y.; Wang, Qinghua; Wheeler, Michael B.

    2010-01-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate pacemaker activity in some cardiac cells and neurons. In the present study, we have identified the presence of HCN channels in pancreatic β-cells. We then examined the functional characterization of these channels in β-cells via modulating HCN channel activity genetically and pharmacologically. Voltage-clamp experiments showed that over-expression of HCN2 in rat β-cells significantly increased HCN current (Ih), whereas expression of dominant-negative HCN2 (HCN2-AYA) completely suppressed endogenous Ih. Compared to control β-cells, over-expression of Ih increased insulin secretion at 2.8 mmol/l glucose. However, suppression of Ih did not affect insulin secretion at both 2.8 mmol/l and 11.1 mmol/l glucose. Current-clamp measurements revealed that HCN2 over-expression significantly reduced β-cell membrane input resistance (Rin), and resulted in a less hyperpolarizing membrane response to the currents injected into the cell. Conversely, dominant negative HCN2-AYA expression led to a substantial increase of Rin, which was associated with a more hyperpolarizing membrane response to the currents injected. Remarkably, under low extracellular potassium conditions (2.5mmol/l K+), suppression of Ih resulted in increased membrane hyperpolarization and decreased insulin secretion. We conclude that Ih in β-cells possess the potential to modulate β-cell membrane potential and insulin secretion under hypokalemic conditions. PMID:19654142

  14. 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

  15. Exocrine pancreatic function of children from the Ivory Coast compared to French children. Effect of kwashiorkor.

    PubMed

    Sauniere, J F; Sarles, H; Attia, Y; Lombardo, A; Yoman, T N; Laugier, R; Manlan, K; Sahel, J

    1986-05-01

    One hundred nineteen children, either French or from the Ivory Coast, aged 1-8 years, were submitted to pancreatic function testing by duodenal aspiration. Trypsin, chymotrypsin, lipase, phospholipase, amylase, volume, bicarbonate, chloride, and calcium were estimated before and after an intravenous injection of 1 CU secretin + 3 CHR units pancreozymin per kilogram of body weight. Sixty-two patients were normal European children, and 11 were normal African children. Twenty-five African children presented with kwashiorkor and 10 African children had presented with kwashiorkor but had recovered at the time of the test. Three cases of recurrent kwashiorkor are also included. In the normal group of African children, phospholipase concentration, volume, and bicarbonate were significantly decreased but chymotrypsin and trypsin concentrations were not, when compared to the normal European population. In kwashiorkor patients, lipase, amylase, phospholipase, and chymotrypsin concentration were significantly decreased compared to normal Africans. Trypsin, volume, and bicarbonate were not affected. These modifications disappeared after refeeding. In cases of recurrent kwashiorkor, all enzymes, including trypsin, were decreased. Calcium was never modified. These modifications were very different from those observed in chronic alcoholic and hypercalcemic pancreatitis. In a two-year study, chronic calcifying pancreatitis (CCP) was diagnosed in 14 patients (13 males), hospitalized in Abidjan. The mean age at onset of the disease was 41 years (SD 12.71), which is very similar to European cases. The most frequent cause was alcoholism, as in Occidental countries. The nutrition of the population was low in protein, calories being provided mostly by manioc, but no apparent symptoms of malnutrition were observed in the parents of our patients.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Modern vestibular function testing.

    PubMed Central

    Baloh, R W; Furman, J M

    1989-01-01

    Current tests of vestibular function concentrate on the horizontal semicircular canal-ocular reflex because it is the easiest reflex to stimulate (calorically and rotationally) and record (using electro-oculography). Tests of the other vestibulo-ocular reflexes (vertical semicircular canal and otolith) and of the vestibulospinal reflexes have yet to be shown useful in the clinical setting. Digital video recording of eye movements and vestibular-evoked responses are promising new technologies that may affect clinical testing in the near future. PMID:2660408

  17. A case of salicylazosulfapyridine (Salazopyrin)-induced acute pancreatitis with positive lymphocyte stimulation test (LST).

    PubMed

    Chiba, M; Horie, Y; Ishida, H; Arakawa, H; Masamune, O

    1987-04-01

    A case of acute pancreatitis induced by salicylazosulfapyridine (Salazopyrin, SASP) was reported. A 33-year-old man with ulcerative colitis was given SASP. Five weeks later, P-type serum amylase was found to be elevated. The amylase/creatinine clearance ratio (ACCR) and serum lipase were also elevated. There were neither subjective symptoms nor abnormal ultrasound findings in the pancrease. Lymphocyte stimulation test (LST) to SASP was positive. Asymptomatic pancreatitis by SASP was suspected and SASP administration was halted. Afterwards the abnormal data became normal. Readministration of SASP because of relapse caused an episode of pancreatitis similar to the first occasion. LST was negative before SASP intake and became positive after intake. Desensitization to SASP was unsuccessful. LST was negative before attempting desensitization and became positive when the dosage of SASP increased to 100 mg daily. This is the second case of acute pancreatitis reported to be induced by SASP and this is the first case in which LST to SASP was described. To our knowledge, this is also the first case in which a positive LST was described in drug-induced pancreatitis. This case provides evidence for the role of delayed type hypersensitivity in the etiopathogenesis of SASP allergy and of dose-independent drug-induced pancreatitis. PMID:2885242

  18. 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.

  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. Effects of leptin replacement therapy on pancreatic β-cell function in patients with lipodystrophy.

    PubMed

    Muniyappa, Ranganath; Brown, Rebecca J; Mari, Andrea; Joseph, Jalaja; Warren, Mary A; Cochran, Elaine K; Skarulis, Monica C; Gorden, Phillip

    2014-04-01

    OBJECTIVE Leptin administration is known to directly modulate pancreatic β-cell function in leptin-deficient rodent models. However, human studies examining the effects of leptin administration on β-cell function are lacking. In this study, we examined the effects (16-20 weeks) of leptin replacement on β-cell function in patients with lipodystrophy. RESEARCH DESIGN AND METHODS In a prospective, open-label, currently ongoing study, we studied the effects of leptin replacement on β-cell function in 13 patients with congenital or acquired lipodystrophy. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution from plasma glucose and C-peptide levels measured during oral glucose tolerance tests (OGTTs) performed at baseline and after 16-20 weeks of leptin replacement. β-Cell glucose sensitivity and rate sensitivity were assessed by mathematical modeling of OGTT. RESULTS There was a significant decrease in triglycerides, free fatty acids, and glycosylated hemoglobin levels (A1C) after leptin therapy. Patients with lipodystrophy have high fasting and glucose-stimulated ISR. However, leptin therapy had no significant effect on fasting ISR, total insulin secretion during OGTT, β-cell glucose sensitivity, rate sensitivity, or insulin clearance. CONCLUSIONS In contrast to the suppressive effects of leptin on β-cell function in rodents, 16-20-week treatment with leptin in lipodystrophy patients did not significantly affect insulin secretion or β-cell function in leptin-deficient individuals with lipodystrophy.

  1. 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

  2. [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.

  3. Decreased pancreatic exocrine function in the mutant Eisai hyperbilirubinemic rat (EHBR).

    PubMed

    Inagaki, T; Hoshino, M; Ohara, H; Yamada, T; Ogasawara, T; Shimizu, H; Itoh, M

    1999-03-01

    The Eisai hyperbilirubinemic rat (EHBR) is a Sprague-Dawley rat (SDR) mutant with conjugated hyperbilirubinemia as an autosomal recessive trait. EHBRs manifest jaundice from birth, which is permanent except for a transient decrease at 6-8 weeks of age. To investigate whether the hyperbilirubinemia affects pancreatic exocrine function and acinar cell growth, EHBRs at 6 (without jaundice) and 12 weeks (with jaundice) of age were compared, along with SDRs as controls. Pancreatic wet weights did not significantly differ, but amylase content of acini was lower in EHBRs than SDRs. No correlation was found between pancreatic wet weight and serum bilirubin levels in EHBRs. In vitro amylase release in response to 1-100 pM cholecystokinin octapeptide (CCK-8), 1 microM 12-O-tetradecanoylphorbol 13-acetate, and 2.5 microM calcium ionophore A23187, and in vivo pancreatic secretion stimulated by CCK-8 (0.08 microg/kg body weight/h) were significantly lower in the EHBR cases than in the SDRs. At the electron microscopic level, many acinar cell nuclei were pyknotic, most elements of their Golgi complexes were atrophied, some mitochondria demonstrated fusion, and the rough-surfaced endoplasmic reticulum (RER) was dilated in EHBRs. These findings are indicative of a hypofunctional state. However, no differences between EHBRs at 6 and 12 weeks of age were evident, suggesting that the hyperbilirubinemia does not exert any pronounced influence on acinar cell growth or pancreatic exocrine function.

  4. 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.

  5. Pancreatitis - children

    MedlinePlus

    ... perform lab tests to check the release of pancreatic enzymes. These include tests to check the: Blood amylase level Blood lipase level Urine amylase level Other blood tests ... the pancreas include: Ultrasound of the abdomen (most common) CT ...

  6. Age-Related Impairment of Pancreatic Beta-Cell Function: Pathophysiological and Cellular Mechanisms

    PubMed Central

    De Tata, Vincenzo

    2014-01-01

    The incidence of type 2 diabetes significantly increases with age. The relevance of this association is dramatically magnified by the concomitant global aging of the population, but the underlying mechanisms remain to be fully elucidated. Here, some recent advances in this field are reviewed at the level of both the pathophysiology of glucose homeostasis and the cellular senescence of pancreatic islets. Overall, recent results highlight the crucial role of beta-cell dysfunction in the age-related impairment of pancreatic endocrine function and delineate the possibility of new original therapeutic interventions. PMID:25232350

  7. 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).

  8. 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.

  9. [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.

  10. SLC26 anion exchangers of guinea pig pancreatic duct: molecular cloning and functional characterization

    PubMed Central

    Stewart, Andrew K.; Shmukler, Boris E.; Vandorpe, David H.; Reimold, Fabian; Heneghan, John F.; Nakakuki, M.; Akhavein, Arash; Ko, Shigeru; Ishiguro, Hiroshi

    2011-01-01

    The secretin-stimulated human pancreatic duct secretes HCO3−-rich fluid essential for normal digestion. Optimal stimulation of pancreatic HCO3− secretion likely requires coupled activities of the cystic fibrosis transmembrane regulator (CFTR) anion channel and apical SLC26 Cl−/HCO3− exchangers. However, whereas stimulated human and guinea pig pancreatic ducts secrete ∼140 mM HCO3− or more, mouse and rat ducts secrete ∼40–70 mM HCO3−. Moreover, the axial distribution and physiological roles of SLC26 anion exchangers in pancreatic duct secretory processes remain controversial and may vary among mammalian species. Thus the property of high HCO3− secretion shared by human and guinea pig pancreatic ducts prompted us to clone from guinea pig pancreatic duct cDNAs encoding Slc26a3, Slc26a6, and Slc26a11 polypeptides. We then functionally characterized these anion transporters in Xenopus oocytes and human embryonic kidney (HEK) 293 cells. In Xenopus oocytes, gpSlc26a3 mediated only Cl−/Cl− exchange and electroneutral Cl−/HCO3− exchange. gpSlc26a6 in Xenopus oocytes mediated Cl−/Cl− exchange and bidirectional exchange of Cl− for oxalate and sulfate, but Cl−/HCO3− exchange was detected only in HEK 293 cells. gpSlc26a11 in Xenopus oocytes exhibited pH-dependent Cl−, oxalate, and sulfate transport but no detectable Cl−/HCO3− exchange. The three gpSlc26 anion transporters exhibited distinct pharmacological profiles of 36Cl− influx, including partial sensitivity to CFTR inhibitors Inh-172 and GlyH101, but only Slc26a11 was inhibited by PPQ-102. This first molecular and functional assessment of recombinant SLC26 anion transporters from guinea pig pancreatic duct enhances our understanding of pancreatic HCO3− secretion in species that share a high HCO3− secretory output. PMID:21593449

  11. 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

  12. 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

  13. 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.

  14. A large functional somatostatinoma in the pancreatic tail: atypical CT appearances.

    PubMed

    Yu, Ri-Sheng; Chen, Ying; Wang, Liu-Hong; Xu, Xiu-Fang; Jiang, Ding-Yao

    2009-12-01

    Somatostatinomas are extremely rare endocrine tumors, and those with diameters above 2 cm are reported to increase the risk of metastasis significantly. We report a case of a large functional somatostatinoma in the pancreatic tail without metastases. A 46-year-old woman with a history of recurrent mild upper abdominal pain and diarrhea for 10 months was admitted to our hospital. Multiple-phase spiral computed tomography revealed a 10 cm x 8 cm, ill-defined, elliptic mass in the body and tail of the pancreas. There was a slightly heterogeneous enhancement on hepatic arterial phase and isodensity to the pancreatic parenchyma with small dotted necrosis within the middle region of the mass on hepatic portal venous and parenchymal phase, with patent splenic vein, dilated collaterals at the splenic hilum and no dilated pancreatic duct, resembling a diffuse infiltration tumor. To the best of our knowledge, this is the first description of multiple-phase spiral computed tomography findings of a functional somatostatinoma in the pancreatic tail and the largest thus far on reported computed tomography, with some differences compared with the previous reports.

  15. 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)

  16. A Scalable System for Production of Functional Pancreatic Progenitors from Human Embryonic Stem Cells

    PubMed Central

    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

  17. 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.

  18. 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

  19. Liver function tests

    MedlinePlus

    ... laboratory results. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods . 22nd ... liver function. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods . 22nd ...

  20. Kidney function tests

    MedlinePlus

    Oh MS. Evaluation of renal function, water, electrolytes and acid-base balance. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods . 22nd ed. Philadelphia, PA: Elsevier Saunders; ...

  1. 13C-labeled mixed triglyceride breath test (13C MTG-BT) in healthy children and children with cystic fibrosis (CF) under pancreatic enzyme replacement therapy (PERT): a pilot study.

    PubMed

    Herzog, Denise C; Delvin, Edgard E; Albert, Caroline; Marcotte, Jacques E; Pelletier, Véronique A; Seidman, Ernest G

    2008-12-01

    The MTG-BT estimates the hydrolysis of triacyl-glycerols by pancreatic lipase, and appears attractive for monitoring exogenous lipase requirements in patients with exocrine pancreatic insufficiency. To assess the test's discrimination capacity and repeatability, 9 CF patients with PERT and 10 healthy children underwent the (13)C-MTG-BT twice, at a 2- to 4-week interval. The test distinguished well between patients with severe exocrine pancreatic insufficiency (SEPI) and healthy subjects. However, within-subject variability for postprandial per thousand(13)C-enrichment and postprandial % dose recovery (PDR) was high in both groups. Therefore, the (13)C-MTG-BT seems useful to distinguish between SEPI and normal exocrine pancreatic function, but requires further development to improve its repeatability.

  2. 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 ...

  3. Thyroid function tests

    MedlinePlus

    ... Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology . 13th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap ... testing. In: Jameson JL, De Groot LJ, eds. Endocrinology: Adult and Pediatric . 7th ed. Philadelphia, PA: Elsevier ...

  4. In vitro lipolysis tests on lipid nanoparticles: comparison between lipase/co-lipase and pancreatic extract.

    PubMed

    Jannin, Vincent; Dellera, Eleonora; Chevrier, Stéphanie; Chavant, Yann; Voutsinas, Christophe; Bonferoni, Cristina; Demarne, Frédéric

    2015-01-01

    Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLC) are lipid nanocarriers aimed to the delivery of drugs characterized by a low bioavailability, such as poorly water-soluble drugs and peptides or proteins. The oral administration of these lipid nanocarriers implies the study of their lipolysis in presence of enzymes that are commonly involved in dietary lipid digestion in the gastrointestinal tract. In this study, a comparison between two methods was performed: on one hand, the lipase/co-lipase assay, commonly described in the literature to study the digestion of lipid nanocarriers, and on the other hand, the lipolysis test using porcine pancreatic extract and the pH-stat apparatus. This pancreatic extract contains both the pancreatic lipase and carboxyl ester hydrolase (CEH) that permit to mimic in a biorelevant manner the duodenal digestive lipolysis. The test was performed by means of a pH-stat apparatus to work at constant pH, 5.5 or 6.25, representing respectively the fasted or fed state pH conditions. The evolution of all acylglycerol entities was monitored during the digestion by sampling the reaction vessel at different time points, until 60 min, and the lipid composition of the digest was analyzed by gas chromatography. SLN and NLC systems obtained with long-chain saturated acylglycerols were rapidly and completely digested by pancreatic enzymes. The pH-stat titration method appears to be a powerful technique to follow the digestibility of these solid lipid-based nanoparticles. PMID:25342478

  5. 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 ...

  6. Pancreatic enzyme replacement therapy during pancreatic insufficiency.

    PubMed

    Berry, Amy J

    2014-06-01

    Pancreatic stimulation and therefore digestion is a tightly controlled and hormonally mediated process. Any alterations affecting any of the systematic steps for successful digestion and absorption to occur will impair appropriate pancreatic enzymatic secretion, entry into the bowel lumen, functionality once inside the lumen, and thus appropriate mixing with foods and nutrients. Many causes of pancreatic insufficiency may require the initiation of pancreatic enzyme therapy, including but not limited to cystic fibrosis, pancreatic cancer, acute and chronic pancreatitis, and pancreatic surgery. This purpose of this article is to help clarify the conditions that cause pancreatic insufficiency, how to determine if the patient is malabsorbing, and the best use of pancreatic enzyme replacement therapy for treatment in these conditions. The first step in determining if pancreatic enzyme therapy is appropriate is to determine if the patient is malabsorbing specifically due to pancreatic exocrine insufficiency. An overview of the methods used to determine pancreatic insufficiency is provided, as well as appropriate treatment methods. Recent Food and Drug Administration regulations require a more thorough process, including randomized controlled trials to prove the safety and efficacy of pancreatic enzymes, to approve them for use. The studies used to verify efficacy also are examined. Last, dosing guidelines and some unconventional ways to administer pancreatic enzymes, such as during enteral feedings, are reviewed.

  7. 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 ...

  8. 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 ... swelling of the pancreas include: CT scan of the abdomen MRI of ...

  9. Malabsorption Blood Test: Assessing Fat Absorption in Patients with Cystic Fibrosis and Pancreatic Insufficiency

    PubMed Central

    Mascarenhas, Maria R.; Mondick, John; Barrett, Jeffrey S.; Wilson, Martha; Stallings, Virginia A.; Schall, Joan I.

    2015-01-01

    The Malabsorption Blood Test (MBT), consisting of pentadecanoic acid (PA), a free fatty acid and triheptadecanoic acid (THA), a triglyceride that requires pancreatic lipase for absorption of the heptadecanoic acid (HA), was developed to assess fat malabsorption in patients with cystic fibrosis (CF) and pancreatic insufficiency (PI). The objective was to construct a population pharmacokinetic (PK) model to describe PA and HA disposition in healthy subjects and CF subjects. A model was simultaneously fit to PA and HA concentrations, consisting of one compartment disposition and a transit model to describe absorption. PA bioavailability estimates for CF subjects without pancreatic enzyme administration [1.07 (0.827,1.42)] and with enzymes [0.88 (0.72,1.09)] indicated PA absorption comparable to healthy subjects. HA bioavailability in CF without enzyme administration was 0.0292 (0.0192,0.0459), and with enzymes increased to 0.606 (0.482,0.823). In CF, compared to taking enzymes with the MBT, HA bioavailability was further decreased by factors of 0.829 (0.664,0.979) and 0.78 (0.491,1.13) with enzymes taken 30 and 60 minutes after MBT, respectively. The MBT detected differences in fat absorption in subjects with CF with and without enzyme administration and with changes in enzyme timing. Future studies will address application of the MBT in CF and other malabsorption diagnoses. PMID:25689042

  10. 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

  11. 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.

  12. [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.

  13. [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

  14. Management of fibrosing pancreatitis in children presenting with obstructive jaundice

    PubMed Central

    Sylvester, F; Shuckett, B; Cutz, E; Durie, P; Marcon, M

    1998-01-01

    Background—Children with fibrosing pancreatitis are conventionally treated surgically to relieve common bile duct (CBD) obstruction caused by pancreatic compression. Residual pancreatic function has not been formally tested in these patients. 
Aims—To evaluate the usefulness of non-surgical temporary drainage in children with fibrosing pancreatitis and to assess pancreatic function after resolution of their CBD obstruction. 
Patients—Four children (1.5-13 years; three girls). 
Methods and results—Abdominal sonography and computed tomography revealed diffuse enlargement of the pancreas, predominantly the head. The CBD was dilated due to compression by the head of the pancreas. Pancreatic biopsy specimens obtained in three patients showed notable acinar cell atrophy and extensive fibrosis. Cystic fibrosis was excluded. No other cause of pancreatitis was identified. Pancreatic tissue from one patient contained viral DNA sequences for parvovirus B19 detected by polymerase chain reaction; serum IgM to parvovirus was positive. Three patients had temporary drainage of the CBD and one patient underwent a choledochojejunostomy. Serial imaging studies revealed resolution of the CBD obstruction with reduction in pancreatic size. Exocrine pancreatic function deteriorated. Three patients developed pancreatic insufficiency within two to four months of presentation. The fourth patient has notably diminished pancreatic function, but remains pancreatic sufficient. None has diabetes mellitus. 
Conclusions—Temporary drainage of the CBD obstruction is recommended in fibrosing pancreatitis in children along with close monitoring of the clinical course, before considering surgery. 

 Keywords: pancreatitis; jaundice; common bile duct obstruction; children PMID:9824357

  15. 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

  16. 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

  17. New insights into fatty acid modulation of pancreatic beta-cell function.

    PubMed

    Haber, Esther P; Procópio, Joaquim; Carvalho, Carla R O; Carpinelli, Angelo R; Newsholme, Philip; Curi, Rui

    2006-01-01

    Insulin resistance states as found in type 2 diabetes and obesity are frequently associated with hyperlipidemia. Both stimulatory and detrimental effects of free fatty acids (FFA) on pancreatic beta cells have long been recognized. Acute exposure of the pancreatic beta cell to both high glucose concentrations and saturated FFA results in a substantial increase of insulin release, whereas a chronic exposure results in desensitization and suppression of secretion. Reduction of plasma FFA levels in fasted rats or humans severely impairs glucose-induced insulin release but palmitate can augment insulin release in the presence of nonstimulatory concentrations of glucose. These results imply that changes in physiological plasma levels of FFA are important for regulation of beta-cell function. Although it is widely accepted that fatty acid (FA) metabolism (notably FA synthesis and/or formation of LC-acyl-CoA) is necessary for stimulation of insulin secretion, the key regulatory molecular mechanisms controlling the interplay between glucose and fatty acid metabolism and thus insulin secretion are not well understood but are now described in detail in this review. Indeed the correct control of switching between FA synthesis or oxidation may have critical implications for beta-cell function and integrity both in vivo and in vitro. LC-acyl-CoA (formed from either endogenously synthesized or exogenous FA) controls several aspects of beta-cell function including activation of certain types of PKC, modulation of ion channels, protein acylation, ceramide- and/or NO-mediated apoptosis, and binding to and activating nuclear transcriptional factors. The present review also describes the possible effects of FAs on insulin signaling. We have previously reported that acute exposure of islets to palmitate up-regulates some key components of the intracellular insulin signaling pathway in pancreatic islets. Another aspect considered in this review is the potential source of fatty acids

  18. [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.

  19. A spheroid-based 3-D culture model for pancreatic cancer drug testing, using the acid phosphatase assay.

    PubMed

    Wen, Z; Liao, Q; Hu, Y; You, L; Zhou, L; Zhao, Y

    2013-07-01

    Current therapy for pancreatic cancer is multimodal, involving surgery and chemotherapy. However, development of pancreatic cancer therapies requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Compared to two-dimensional culture of cell monolayer, three-dimensional (3-D) models more closely mimic native tissues, since the tumor microenvironment established in 3-D models often plays a significant role in cancer progression and cellular responses to the drugs. Accumulating evidence has highlighted the benefits of 3-D in vitro models of various cancers. In the present study, we have developed a spheroid-based, 3-D culture of pancreatic cancer cell lines MIAPaCa-2 and PANC-1 for pancreatic drug testing, using the acid phosphatase assay. Drug efficacy testing showed that spheroids had much higher drug resistance than monolayers. This model, which is characteristically reproducible and easy and offers rapid handling, is the preferred choice for filling the gap between monolayer cell cultures and in vivo models in the process of drug development and testing for pancreatic cancer.

  20. Bile exclusion from the duodenum. Its effect on gastric and pancreatic function in the dog.

    PubMed

    Davies, H A; Wheeler, M H; Psaila, J; Rhodes, J; Newcombe, R G; Jones, J M; Procter, D; Adrian, T E; Bloom, S R

    1985-10-01

    The effect of diverting bile from the duodenum in four dogs with cholecystojejunostomy was studied using a double-marker perfusion technique. After the diversion procedure, a liquid meal increased acid secretion from 0.8 mmol H+/min to 1.48 mmol H+/min (P less than 0.05, paired t test); there was an associated rise in serum levels of gastrin 120 min after feeding (P less than 0.001, paired t test). Pancreatic secretion of trypsin decreased from 3.91 IU/min to 2.66 IU/min after bile diversion (P less than 0.01, paired t test), and the level of CCK was significantly lower 60 min after feeding (P less than 0.05, paired t test). There was no significant change in the rate of gastric emptying after bile diversion, but the pH of duodenal contents was lower in the later stages of digestion. These changes may explain the reported increase of peptic ulcer after diverting bile from the duodenum, and the procedure should not be considered unless the consequences of acid hypersecretion and pancreatic inhibition have been anticipated.

  1. Hereditary Pancreatitis.

    PubMed

    Rivera Rivera, Edgardo D; Chugh, Ankur; Cordova, Jonathon; Young, Sona

    2016-02-01

    A 13-year-old boy with a strong family history of hereditary pancreatitis was found to have a PRSS1 mutation after being tested at age 5 years during his first documented incident of pancreatitis. Since then, a multidisciplinary team has been treating him for the diagnosis of hereditary pancreatitis. His pain episodes increased in severity over the past several months such that the pain began to severely interfere with his daily life. After extensive discussion, a total pancreatectomy with auto islet cell transplant was performed. He is now pain free and does not require any insulin. This leads us to the questions of what is hereditary pancreatitis and how is it diagnosed? What are the management and follow-up strategies needed for these patients? This article addresses these questions and informs the reader about this diagnosis and the importance of having a high index of clinical suspicion. PMID:26878183

  2. Ape1 regulates WNT/β-catenin signaling through its redox functional domain in pancreatic cancer cells.

    PubMed

    Jiang, Shaojie; Zhu, Lina; Tang, Haimei; Zhang, Miaofeng; Chen, Zhihua; Fei, Jian; Han, Baosan; Zou, Gang-Ming

    2015-08-01

    Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1, Ape1) is a multifunctional protein that is upregulated in human pancreatic cancer. Ape1 redox domain plays an essential role in regulating the effects of reactive oxygen species (ROS) generated during physiological metabolism and pathological stress. In the present study, we explored whether Ape1 and ROS affect WNT/β-catenin signaling. We used E3330, a small molecule inhibitor of the redox activity of Ape1, and a siRNA approach to knock down Ape1, in two human pancreatic cancer cell lines. Inhibition of Ape1 resulted in growth suppression of pancreatic cancer cells, increased ROS levels, upregulation of β-catenin and c-myc and downregulation of cyclin D1. Consistent with these data, overexpression of Ape1 in pancreatic cancer cells reduced ROS and c-myc levels and increased cyclin D1 levels. Moreover, treatment of pancreatic cancer cells with H2O2 to induce oxidative stress resulted in upregulated ROS levels, decreased Ape1 at both the mRNA and protein level, and alterations in WNT/β-catenin pathway components. Finally, treatment of pancreatic cancer cells with the WNT/β-catenin inhibitor IWR-1 resulted in growth inhibition, which was greatly enhanced when combined with E3330 treatment. In summary, our results demonstrate that ROS is an important intracellular messenger that can modulate WNT/β‑catenin signaling. The present study provides interesting new insight into crosstalk between the redox function of Ape1 and WNT/β-catenin signaling in cancer cells. Furthermore, our data show that the combination of Ape1 and WNT inhibitors enhanced the inhibition of pancreatic cell proliferation. These results provide a promising novel therapeutic strategy for treating pancreatic cancer in future.

  3. Bestrophin expression and function in the human pancreatic duct cell line, CFPAC-1

    PubMed Central

    Marsey, Laura L; Winpenny, John P

    2009-01-01

    Pancreatic duct epithelial cells (PDECs) have been shown to express calcium activated chloride channels (CaCCs) and there is evidence for their involvement in fluid secretion from these cells. The molecular identity of the CaCC in PDECs remains unknown. Recently, the bestrophin family of proteins have been proposed as a potential molecular candidate for CaCCs. Expression of bestrophins is strongly correlated with the function of CaCCs in a variety of tissues. In the present study, the expression of bestrophins has been investigated in the cystic fibrosis pancreatic duct cell line, CFPAC-1. Iodide efflux analysis was used to characterise native CaCCs in CFPAC-1 cell monolayers. Efflux was induced with the addition of UTP (100 μm, 10.2 ± 1.5 nmol min−1), which was blocked by the chloride channel blockers niflumic acid (81%) and DIDS (90%). The UTP-stimulated iodide efflux was shown to be Ca2+ dependent and cAMP independent. RT-PCR analysis of RNA isolated from CFPAC-1 cells demonstrated positive identification of all four human bestrophin mRNAs. Western blot of CFPAC-1 cell protein isolates with antibodies specific to human bestrophin 1 (hBest1) showed that hBest1 protein was expressed in this cell line. HBest1 was present on the cell surface, demonstrated using biotinylation and confocal imaging, as well as in the cytoplasm. SiRNA-mediated silencing of hBest1 in CFPAC-1 cells reduced the UTP-stimulated iodide efflux by around 40%. This study provides evidence that the bestrophins are expressed in pancreatic duct cells and, more specifically, that hBest1 plays a role in the CaCCs found in these cells. PMID:19237432

  4. 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

  5. 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

  6. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function.

    PubMed

    Viale, Andrea; Pettazzoni, Piergiorgio; Lyssiotis, Costas A; Ying, Haoqiang; Sánchez, Nora; Marchesini, Matteo; Carugo, Alessandro; Green, Tessa; Seth, Sahil; Giuliani, Virginia; Kost-Alimova, Maria; Muller, Florian; Colla, Simona; Nezi, Luigi; Genovese, Giannicola; Deem, Angela K; Kapoor, Avnish; Yao, Wantong; Brunetto, Emanuela; Kang, Ya'an; Yuan, Min; Asara, John M; Wang, Y Alan; Heffernan, Timothy P; Kimmelman, Alec C; Wang, Huamin; Fleming, Jason B; Cantley, Lewis C; DePinho, Ronald A; Draetta, Giulio F

    2014-10-30

    Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in western countries, with a median survival of 6 months and an extremely low percentage of long-term surviving patients. KRAS mutations are known to be a driver event of PDAC, but targeting mutant KRAS has proved challenging. Targeting oncogene-driven signalling pathways is a clinically validated approach for several devastating diseases. Still, despite marked tumour shrinkage, the frequency of relapse indicates that a fraction of tumour cells survives shut down of oncogenic signalling. Here we explore the role of mutant KRAS in PDAC maintenance using a recently developed inducible mouse model of mutated Kras (Kras(G12D), herein KRas) in a p53(LoxP/WT) background. We demonstrate that a subpopulation of dormant tumour cells surviving oncogene ablation (surviving cells) and responsible for tumour relapse has features of cancer stem cells and relies on oxidative phosphorylation for survival. Transcriptomic and metabolic analyses of surviving cells reveal prominent expression of genes governing mitochondrial function, autophagy and lysosome activity, as well as a strong reliance on mitochondrial respiration and a decreased dependence on glycolysis for cellular energetics. Accordingly, surviving cells show high sensitivity to oxidative phosphorylation inhibitors, which can inhibit tumour recurrence. Our integrated analyses illuminate a therapeutic strategy of combined targeting of the KRAS pathway and mitochondrial respiration to manage pancreatic cancer.

  7. [New aspects of pancreatic beta cell functions and their possible therapeutic applications].

    PubMed

    Tiedge, M

    2006-12-01

    Using the metabolic stimulus-secretion coupling of pancreatic beta cells as an example, this review illustrates how new strategies in the treatment of type 2 diabetes mellitus can be developed from the results of basic research. Metabolic stimulus-secretion coupling presupposes the metabolizing of those stimuli of insulin secretion that have the properties of nutritional substances. Changes in the ATP/ADP ratio within the beta cells will then trigger the release of insulin granules from them. Glucokinase, a glucose phosphorylating enzyme, functions as a metabolic glucose sensor, which couples changes in physiological glucose concentration in the pancreatic beta cells and in the liver to the intermediary metabolism, i.e. glycolysis, the citrate cycle and respiratory-chain phosphorylation. In this way insulin secretion and hepatic metabolism are positively influenced. Several pharmaceutical companies (Roche, Merck, Astra-Zeneca, Lilly) have recently developed first examples of glucokinase-activating compounds and demonstrated in animal models their efficacy in the treatment of type 2 diabetes mellitus. These glucokinase activators prevent glucokinase from changing into a catalytically inactive structure. They also increase glucose affinity of the enzyme and stabilize a catalytically active form of glucokinase proteins. In this way glucokinase activators increase glucose-induced insulin secretion and inhibit hepatic glucogenesis. Glucokinase activators are an interesting innovation in the future treatment of type 2 diabetes, because their action on beta cells and the liver is caused by changes in blood glucose concentration.

  8. Metformin Restrains Pancreatic Duodenal Homeobox-1 (PDX-1) Function by Inhibiting ERK Signaling in Pancreatic Ductal Adenocarcinoma.

    PubMed

    Zhou, G; Yu, J; Wang, A; Liu, S-H; Sinnett-Smith, J; Wu, J; Sanchez, R; Nemunaitis, J; Ricordi, C; Rozengurt, E; Brunicardi, F C

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most potent and perilous diseases known, with a median survival rate of 3-5 months due to the combination of only advanced stage diagnosis and ineffective therapeutic options. Metformin (1,1-Dimethylbiguanide hydrochloride), the leading drug used for type 2 diabetes mellitus, emerges as a potential therapy for PDAC and other human cancers. Metformin exerts its anticancer action via a variety of adenosine monophosphate (AMP)-activated protein kinase (AMPK)- dependent and/or AMPK-independent mechanisms. We present data here showing that metformin downregulated pancreatic transcription factor pancreatic duodenal homeobox-1 (PDX-1), suggesting a potential novel mechanism by which metformin exerts its anticancer action. Metformin inhibited PDX-1 expression at both protein and mRNA levels and PDX-1 transactivity as well in PDAC cells. Extracellular signal-regulated kinase (ERK) was identified as a PDX-1-interacting protein by antibody array screening in GFP-PDX-1 stable HEK293 cells. Co-transfection of ERK1 with PDX-1 resulted in an enhanced PDX-1 expression in HEK293 cells in a dose-dependent manner. Immunoprecipitation/Western blotting analysis confirmed the ERK-PDX-1 interaction in PANC-1 cells stimulated by epidermal growth factor (EGF). EGF induced an enhanced PDX-1 expression in PANC-1 cells and this stimulation was inhibited by MEK inhibitor PD0325901. Metformin inhibited EGF-stimulated PDX-1 expression with an accompanied inhibition of ERK kinase activation in PANC- 1 cells. Taken together, our studies show that PDX-1 is a potential novel target for metformin in PDAC cells and that metformin may exert its anticancer action in PDAC by down-regulating PDX-1 via a mechanism involving inhibition of ERK signaling.

  9. Modified Da Chengqi granules improvement in immune function in early severe acute pancreatitis patients.

    PubMed

    Jiang, D-L; Yang, J; Jiang, S-Y; Yuan, F-L; Gu, Y-L; Li, J-P; Pei, Z-J

    2016-01-01

    We investigated the role of modified Da Chengqi granules in improving immune function in early severe acute pancreatitis patients. Early severe acute pancreatitis patients who agreed to receive combined treatment of traditional Chinese and Western medicine were randomly assigned to the experimental or control group. All subjects received conventional therapy to support organ function. The experimental group also received modified Da Chengqi granules. Cytokine (interleukin-6, interleukin-10, and tumor necrosis factor-α) levels, immunological markers (HLA-DR, Treg, and Th1/Th2), urinary lactulose/mannitol ratio, and endotoxin levels were measured at 1, 3, 7, and 14 days after hospital admission. The total mortality rate was 11.69% (9/77), which was significantly lower in the experimental group [4.88% (2/41)] than in the control group [19.44% (7/36); χ(2) = 3.940, P < 0.05]. Serum interleukin-6, interleukin-10, tumor necrosis factor-α and endotoxin levels and the lactulose/mannitol ratio were significantly lower on day 7 and day 14 than on day 1 in experimental and control groups (P < 0.01). Immunological indices were significantly lower in the experimental group than in the control group on day 14 (all P < 0.01 or 0.05). HLA-DR-positive cell ratio gradually increased over 14 days in experimental and control groups (P < 0.01 vs day 1), but was higher in the experimental group than in the control group by day 14 (P < 0.05). Notably, Treg cell prevalence and Th1/Th2 cell ratio deteriorated within 7 days in both groups (P < 0.01 vs day 1), but then returned to day 1 levels (P < 0.01 or 0.05 vs day 1). Significant differences in Treg levels and Th1/Th2 cell ratio between experimental and control groups were observed on day 14 (P < 0.01). These results show that modified Da Chengqi granules can improve immune function in early severe acute pancreatitis patients.

  10. [Functional distinction of secreting pools of the pancreas and participation of the pancreatic ductal system in the development of the pancreatic secret properties].

    PubMed

    Korot'ko, G F; Voskanian, S E; Gladkiĭ, E Iu; Makarova, T M; Bulgakov, V A

    2002-08-01

    Acute experiments on dogs with separate secretion of the pancreatic enzymes, either stimulated or inhibited, from two lobes of pancreas, and investigation into the character of kinetics of the secretion from 5-7 ductal pools of the pancreas showed the functional specifics, with the device of ductal valves and microdepot of a secret of the pancreas ductal system playing an important role. The conclusion is made that the final secret of pancreas removed to the duodenum is a product of a secret-motor activation of non-equipotentional microregions of the gland, being the components of an intervisceral dynamical mosaic.

  11. Extracellular matrix composition significantly influences pancreatic stellate cell gene expression pattern: role of transgelin in PSC function.

    PubMed

    Apte, Minoti V; Yang, Lu; Phillips, Phoebe A; Xu, Zhihong; Kaplan, Warren; Cowley, Mark; Pirola, Romano C; Wilson, Jeremy S

    2013-09-15

    Activated pancreatic stellate cells (PSCs) are responsible for the fibrotic matrix of chronic pancreatitis and pancreatic cancer. In vitro protocols examining PSC biology have usually involved PSCs cultured on plastic, a nonphysiological surface. However, PSCs cultured on physiological matrices, e.g., Matrigel (normal basement membrane) and collagen (fibrotic pancreas), may have distinctly different behaviors compared with cells cultured on plastic. Therefore, we aimed to 1) compare PSC gene expression after culture on plastic, Matrigel, and collagen I; 2) validate the gene array data for transgelin, the most highly dysregulated gene in PSCs grown on activating vs. nonactivating matrices, at mRNA and protein levels; 3) examine the role of transgelin in PSC function; and 4) assess transgelin expression in human chronic pancreatitis sections. Culture of PSCs on different matrices significantly affected their gene expression pattern. 146, 619, and 432 genes, respectively, were differentially expressed (P < 0.001) in PSCs cultured on collagen I vs. Matrigel, Matrigel vs. plastic, and collagen I vs. plastic. The highest fold change (12.5-fold upregulation) in gene expression in cells on collagen I vs. Matrigel was observed for transgelin (an actin stress fiber-associated protein). Transgelin was significantly increased in activated PSCs vs. quiescent PSCs. Silencing transgelin expression decreased PSC proliferation and also reduced platelet-derived growth factor-induced PSC migration. Notably, transgelin was highly expressed in chronic pancreatitis in stromal areas and periacinar spaces but was absent in acinar cells. These findings suggest that transgelin is a potentially useful target protein to modulate PSC function so as to ameliorate pancreatic fibrosis. PMID:23868411

  12. Pancreatitis - discharge

    MedlinePlus

    Chronic pancreatitis - discharge; Pancreatitis - chronic - discharge; Pancreatic insufficiency - discharge; Acute pancreatitis - discharge ... fluids through an intravenous (IV) tube in your vein and nutrition through a feeding tube or IV. ...

  13. Hereditary pancreatitis for the endoscopist.

    PubMed

    Patel, Milan R; Eppolito, Amanda L; Willingham, Field F

    2013-03-01

    Hereditary pancreatitis shares a majority of clinical and morphologic features with chronic alcoholic pancreatitis, but may present at an earlier age. The term hereditary pancreatitis has primarily been associated with mutations in the serine protease 1 gene (PRSS1) which encodes for cationic trypsinogen. PRSS1 mutations account for approximately 68-81% of hereditary pancreatitis. Mutations in other genes, primarily serine protease inhibitor Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) are also associated with hereditary pancreatitis. While chronic alcoholic pancreatitis may develop in the fourth or fifth decades, patients with hereditary pancreatitis may develop symptoms in the first or second decades of life. Hereditary pancreatitis is diagnosed either by detecting a causative gene mutation or by the presence of chronic pancreatitis in two first-degree or three second-degree relatives, in two or more generations, without precipitating factors and with a negative workup for known causes. Patients with hereditary pancreatitis may have recurrent acute pancreatitis and may develop pancreatic exocrine and endocrine insufficiency. Hereditary pancreatitis may involve premature trypsinogen activation or decreased control of trypsin. Recurrent inflammation can lead to acute pancreatitis and subsequently to chronic pancreatitis with parenchymal calcification. There is a markedly increased risk of pancreatic carcinoma compared with the general population. Patients are often referred for evaluation of pancreatitis, biliary or pancreatic ductal dilatation, jaundice, biliary obstruction, pancreatic duct stone or stricture, pancreatic pseudocysts, and for evaluation for malignancy. Medical treatment includes pancreatic enzyme supplementation, nutritional supplementation, diabetes management, and palliation of pain. Patients should avoid tobacco use and alcohol exposure. Hereditary pancreatitis is reviewed and recommendations for

  14. 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.

  15. Sympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation

    PubMed Central

    Borden, Philip; Houtz, Jessica; Leach, Steven D.; Kuruvilla, Rejji

    2013-01-01

    Summary Sympathetic neurons depend on target-derived neurotrophic cues to control their survival and growth. However, whether sympathetic innervation contributes reciprocally to the development of target tissues is less clear. Here, we report that sympathetic innervation is necessary for the formation of the pancreatic islets of Langerhans and for their functional maturation. Genetic or pharmacological ablation of sympathetic innervation during development resulted in altered islet architecture, reduced insulin secretion and impaired glucose tolerance in mice. Similar defects were observed with pharmacological blockade of β-adrenergic signaling. Conversely, the administration of a β-adrenergic agonist restored islet morphology and glucose tolerance in de-innervated animals. Furthermore, in neuron-islet co-cultures, sympathetic neurons promoted islet cell migration in a β-adrenergic dependent manner. This study reveals that islet architecture requires extrinsic inductive cues from neighboring tissues such as sympathetic nerves, and suggests that early perturbations in sympathetic innervation might underlie metabolic disorders. PMID:23850289

  16. 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

  17. 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

  18. 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

  19. [Pancreatic ultrasonography].

    PubMed

    Fernández-Rodríguez, T; Segura-Grau, A; Rodríguez-Lorenzo, A; Segura-Cabral, J M

    2015-04-01

    Despite the recent technological advances in imaging, abdominal ultrasonography continues to be the first diagnostic test indicated in patients with a suspicion of pancreatic disease, due to its safety, accessibility and low cost. It is an essential technique in the study of inflammatory processes, since it not only assesses changes in pancreatic parenchyma, but also gives an indication of the origin (bile or alcoholic). It is also essential in the detection and tracing of possible complications as well as being used as a guide in diagnostic and therapeutic punctures. It is also the first technique used in the study of pancreatic tumors, detecting them with a sensitivity of around 70% and a specificity of 90%.

  20. Incorporation of Bone Marrow Cells in Pancreatic Pseudoislets Improves Posttransplant Vascularization and Endocrine Function

    PubMed Central

    Wittig, Christine; Laschke, Matthias W.; Scheuer, Claudia; Menger, Michael D.

    2013-01-01

    Failure of revascularization is known to be the major reason for the poor outcome of pancreatic islet transplantation. In this study, we analyzed whether pseudoislets composed of islet cells and bone marrow cells can improve vascularization and function of islet transplants. Pancreatic islets isolated from Syrian golden hamsters were dispersed into single cells for the generation of pseudoislets containing 4×103 cells. To create bone marrow cell-enriched pseudoislets 2×103 islet cells were co-cultured with 2×103 bone marrow cells. Pseudoislets and bone marrow cell-enriched pseudoislets were transplanted syngeneically into skinfold chambers to study graft vascularization by intravital fluorescence microscopy. Native islet transplants served as controls. Bone marrow cell-enriched pseudoislets showed a significantly improved vascularization compared to native islets and pseudoislets. Moreover, bone marrow cell-enriched pseudoislets but not pseudoislets normalized blood glucose levels after transplantation of 1000 islet equivalents under the kidney capsule of streptozotocin-induced diabetic animals, although the bone marrow cell-enriched pseudoislets contained only 50% of islet cells compared to pseudoislets and native islets. Fluorescence microscopy of bone marrow cell-enriched pseudoislets composed of bone marrow cells from GFP-expressing mice showed a distinct fraction of cells expressing both GFP and insulin, indicating a differentiation of bone marrow-derived cells to an insulin-producing cell-type. Thus, enrichment of pseudoislets by bone marrow cells enhances vascularization after transplantation and increases the amount of insulin-producing tissue. Accordingly, bone marrow cell-enriched pseudoislets may represent a novel approach to increase the success rate of islet transplantation. PMID:23875013

  1. [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

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

    PubMed

    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

  3. [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

  4. Islet Autoimmunity Identifies a Unique Pattern of Impaired Pancreatic Beta-Cell Function, Markedly Reduced Pancreatic Beta Cell Mass and Insulin Resistance in Clinically Diagnosed Type 2 Diabetes

    PubMed Central

    Subauste, Angela; Gianani, Roberto; Chang, Annette M.; Plunkett, Cynthia; Pietropaolo, Susan L.; Zhang, Ying-Jian; Barinas-Mitchell, Emma; Kuller, Lewis H.; Galecki, Andrzej; Halter, Jeffrey B.; Pietropaolo, Massimo

    2014-01-01

    There is a paucity of literature describing metabolic and histological data in adult-onset autoimmune diabetes. This subgroup of diabetes mellitus affects at least 5% of clinically diagnosed type 2 diabetic patients (T2DM) and it is termed Latent Autoimmune Diabetes in Adults (LADA). We evaluated indexes of insulin secretion, metabolic assessment, and pancreatic pathology in clinically diagnosed T2DM patients with and without the presence of humoral islet autoimmunity (Ab). A total of 18 patients with at least 5-year duration of clinically diagnosed T2DM were evaluated in this study. In those subjects we assessed acute insulin responses to arginine, a glucose clamp study, whole-body fat mass and fat-free mass. We have also analyzed the pancreatic pathology of 15 T2DM and 43 control cadaveric donors, using pancreatic tissue obtained from all the T2DM organ donors available from the nPOD network through December 31, 2013. The presence of islet Ab correlated with severely impaired β-cell function as demonstrated by remarkably low acute insulin response to arginine (AIR) when compared to that of the Ab negative group. Glucose clamp studies indicated that both Ab positive and Ab negative patients exhibited peripheral insulin resistance in a similar fashion. Pathology data from T2DM donors with Ab or the autoimmune diabetes associated DR3/DR4 allelic class II combination showed reduction in beta cell mass as well as presence of autoimmune-associated pattern A pathology in subjects with either islet autoantibodies or the DR3/DR4 genotype. In conclusion, we provide compelling evidence indicating that islet Ab positive long-term T2DM patients exhibit profound impairment of insulin secretion as well as reduced beta cell mass seemingly determined by an immune-mediated injury of pancreatic β-cells. Deciphering the mechanisms underlying beta cell destruction in this subset of diabetic patients may lead to the development of novel immunologic therapies aimed at halting the

  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. 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

  7. 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?

  8. 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

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

    PubMed Central

    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.

    2015-01-01

    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

  10. Purification and functional characterization of pancreatic insulin from camel (Camelus dromedarius)

    PubMed Central

    Elamin, Babiker A.; Al-Maleki, Abdulmajeed; Ismael, Mohammad A.; Ayoub, Mohammed Akli

    2014-01-01

    Large-scale production of insulin still represents the key step in helping diabetic patients throughout the world. Many species and approaches have been used for the production of insulin. In this study, we purified and characterized for the first time pancreatic insulin from the Arabian camel (Camelus dromedarius) using a modified acid-alcohol extraction method. After extraction insulin was purified using a one-step gel filtration on a Sephadex G-50 column leading to a purification yield of 80 mg/kg (20%) of camel pancreas. The purity of camel insulin was assessed by SDS–PAGE and HPLC using insulin from human, bovine and porcine as standards. Molecular weight was determined for purified camel insulin as 5800 Daltons and its amino acid composition is similar to that known for other species. The functional characterization of purified crude camel insulin was demonstrated in vitro by positive competition by radioimmunoassay and in vivo showing camel insulin inducing acute hypoglycaemia in mice. Together, our study reports for the first time the successful purification of functional insulin from camel pancreas with similar properties compared to other insulin species. This is of great interest given that the camel represents considerable economic worth in many countries. PMID:25473366

  11. Pancreatic triacylglycerol lipase in a hibernating mammal. II. Cold-adapted function and differential expression.

    PubMed

    Squire, Teresa L; Lowe, Mark E; Bauer, Vernon W; Andrews, Matthew T

    2003-12-16

    Thirteen-lined ground squirrels (Spermophilus tridecemlineatus) exploit the low-temperature activity of pancreatic triacylglycerol lipase (PTL) during hibernation. Lipolytic activity at body temperatures associated with hibernation was examined using recombinant ground squirrel and human PTLs expressed in yeast. Both the human and ground squirrel enzymes displayed high activity at temperatures as low as 0 degrees C and showed Q10 values of 1.2-1.5 over a range of 37-7 degrees C. These studies indicate that low-temperature lipolysis is a general property of PTL and does not require protein modifications unique to mammalian cells and/or the hibernating state. Western blots show elevated levels of PTL protein during hibernation in both heart and white adipose tissue (WAT). Significant increases in PTL gene expression are seen in heart, WAT, and testes; but not in pancreas, where PTL mRNA levels are highest. Upregulation of PTL in testes is also accompanied by expression of the PTL-specific cofactor, colipase. The multi-tissue expression of PTL during hibernation supports its role as a key enzyme that shows high activity at low temperatures.

  12. 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...

  13. 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...

  14. 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...

  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. 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

  18. 14 CFR 35.40 - Functional test.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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 in... representative engine on a test stand or on an airplane. The propeller must complete these tests without...

  19. 14 CFR 35.40 - Functional test.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 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 in... representative engine on a test stand or on an airplane. The propeller must complete these tests without...

  20. 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

  1. 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

  2. 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.

  3. 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


  4. [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

  5. [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.

  6. 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 ...

  7. Limitation of amylase creatinine clearance ratio as a diagnostic test for postoperative pancreatitis.

    PubMed

    Wapnick, S; Evans, M I; Hadas, N; Grosberg, S J

    1980-05-01

    The mean +/- S.E.M. ratio of amylase to creatinine clearance significantly increased at 24 hours after operations on the stomach and gallbladder but not after operations at sites remote from the abdominal cavity. Clinically, the elevated amylase to creatinine clearance ratio was not accompanied by pancreatitis. In dogs, surgical handling of the pancreas alone caused a significant increase in this measurement. The amylase to creatinine clearance ratio is not likely to be helpful in predicting the rare, but serious, postoperative complication of pancreatitis.

  8. Maternal high-fat diet induces insulin resistance and deterioration of pancreatic β-cell function in adult offspring with sex differences in mice.

    PubMed

    Yokomizo, Hisashi; Inoguchi, Toyoshi; Sonoda, Noriyuki; Sakaki, Yuka; Maeda, Yasutaka; Inoue, Tomoaki; Hirata, Eiichi; Takei, Ryoko; Ikeda, Noriko; Fujii, Masakazu; Fukuda, Kei; Sasaki, Hiroyuki; Takayanagi, Ryoichi

    2014-05-15

    Intrauterine environment may influence the health of postnatal offspring. There have been many studies on the effects of maternal high-fat diet (HFD) on diabetes and glucose metabolism in offspring. Here, we investigated the effects in male and female offspring. C57/BL6J mice were bred and fed either control diet (CD) or HFD from conception to weaning, and offspring were fed CD or HFD from 6 to 20 wk. At 20 wk, maternal HFD induced glucose intolerance and insulin resistance in offspring. Additionally, liver triacylglycerol content, adipose tissue mass, and inflammation increased in maternal HFD. In contrast, extending previous observations, insulin secretion at glucose tolerance test, islet area, insulin content, and PDX-1 mRNA levels in isolated islets were lower in maternal HFD in males, whereas they were higher in females. Oxidative stress in islets increased in maternal HFD in males, whereas there were no differences in females. Plasma estradiol levels were lower in males than in females and decreased in offspring fed HFD and also decreased by maternal HFD, suggesting that females may be protected from insulin deficiency by inhibiting oxidative stress. In conclusion, maternal HFD induced insulin resistance and deterioration of pancreatic β-cell function, with marked sex differences in adult offspring accompanied by adipose tissue inflammation and liver steatosis. Additionally, our results demonstrate that potential mechanisms underlying sex differences in pancreatic β-cell function may be related partially to increases in oxidative stress in male islets and decreased plasma estradiol levels in males.

  9. 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

  10. Expression, localization, and functional role for synaptotagmins in pancreatic acinar cells

    PubMed Central

    Falkowski, Michelle A.; Thomas, Diana D. H.; Messenger, Scott W.; Martin, Thomas F.

    2011-01-01

    Secretagogue-induced changes in intracellular Ca2+ play a pivotal role in secretion in pancreatic acini yet the molecules that respond to Ca2+ are uncertain. Zymogen granule (ZG) exocytosis is regulated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes. In nerve and endocrine cells, Ca2+-stimulated exocytosis is regulated by the SNARE-associated family of proteins termed synaptotagmins. This study examined a potential role for synaptotagmins in acinar secretion. RT-PCR revealed that synaptotagmin isoforms 1, 3, 6, and 7 are present in isolated acini. Immunoblotting and immunofluorescence using three different antibodies demonstrated synaptotagmin 1 immunoreactivity in apical cytoplasm and ZG fractions of acini, where it colocalized with vesicle-associated membrane protein 2. Synaptotagmin 3 immunoreactivity was detected in membrane fractions and colocalized with an endolysosomal marker. A potential functional role for synaptotagmin 1 in secretion was indicated by results that introduction of synaptotagmin 1 C2AB domain into permeabilized acini inhibited Ca2+-dependent exocytosis by 35%. In contrast, constructs of synaptotagmin 3 had no effect. Confirmation of these findings was achieved by incubating intact acini with an antibody specific to the intraluminal domain of synaptotagmin 1, which is externalized following exocytosis. Externalized synaptotagmin 1 was detected exclusively along the apical membrane. Treatment with CCK-8 (100 pM, 5 min) enhanced immunoreactivity by fourfold, demonstrating that synaptotagmin is inserted into the apical membrane during ZG fusion. Collectively, these data indicate that acini express synaptotagmin 1 and support that it plays a functional role in secretion whereas synaptotagmin 3 has an alternative role in endolysosomal membrane trafficking. PMID:21636530

  11. [Role of procalcitonin rapid test in the differential diagnosis of uninfected and infected forms of acute pancreatitis].

    PubMed

    Makay, Roland; Issekutz, Akos; Banga, Péter; Belágyi, Tibor; Oláh, Attila

    2003-02-01

    We analysed the clinical value of the procalcitonin quick test (PCT-Q; BRAHMS Diagnostica, GmbH, Berlin) in infected pancreatic necrosis verified by guided fine-needle aspiration (FNA). In a prospective, controlled study the results of 24 patients were evaluated during 2001. PCT-Q test was performed in patients with necrosis verified on CT scan and/or septic symptoms. If PCT-Q test was positive or septic complication (infected necrosis or abscess) developed CT or US guided fine-needle aspiration was performed with Gram staining and bacterial culture of the sample. Positive FNA result was indication for surgery with repeated staining and bacterial culture of the surgical specimen. Septic complications of pancreatic origin developed in 12 patients. Comparing the results fine-needle aspiration was more authentic with a sensitivity of 92% and a specificity of 100%, while the sensitivity of the PCT-Q test remained 75% and its specificity 83%. Comparing abscess and infected necrosis, significantly higher procalcitonin values were detected in patients with necrosis. These results show that PCT-Q test can be a possible non-invasive method besides fine-needle aspiration. Elevated levels of procalcitonin (higher than 2 ng/ml) clearly suggest infection of the necrosis, while lower values do not exclude the possibility of local septic progression.

  12. 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 ...

  13. 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 ...

  14. 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 ...

  15. 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 ...

  16. [The epidemiology of pancreatic cancer].

    PubMed

    Lakatos, Gábor; Tulassay, Zsolt

    2010-10-31

    Pancreatic cancer is a relatively uncommon tumor, but even with early diagnosis, mortality rates are high, explaining why this form of cancer has now become a common cause of cancer mortality. There are no screening tests for early detection of pancreatic cancer. It is more common in men than women and is predominantly a disease of elderly people. There is wide variation in the incidence of pancreatic cancer around the world, suggesting that environmental factors are important in the pathogenesis. Smoking is the major known risk factor for pancreatic cancer, while dietary factors seem to be less important. Other possible risk factors include chronic pancreatitis, obesity and type 2 diabetes. Numerous inherited germ line mutations are associated with pancreatic cancer. Of these, hereditary pancreatitis confers the greatest risk, while BRCA2 mutations are the commonest inherited disorder. Polymorphisms in genes that control detoxification of environmental carcinogens and metabolic pathways may alter the risk of pancreatic cancer.

  17. Sweat testing to evaluate autonomic function

    PubMed Central

    Illigens, Ben M.W.; Gibbons, Christopher H.

    2011-01-01

    Sudomotor dysfunction is one of the earliest detectable neurophysiologic abnormalities in distal small fiber neuropathy. Traditional neurophysiologic measurements of sudomotor function include thermoregulatory sweat testing (TST), quantitative sudomotor axon reflex testing (QSART), silicone impressions, the sympathetic skin response (SSR), and the recent addition of quantitative direct and indirect axon reflex testing (QDIRT). These testing techniques, when used in combination, can detect and localized pre- and postganglionic lesions, can provide early diagnosis of sudomotor dysfunction and can monitor disease progression or disease recovery. In this article, we review the common tests available for assessment of sudomotor function, detail the testing methodology, review the limitations and provide examples of test results. PMID:18989618

  18. Histopathologically Proven Autoimmune Pancreatitis Mimicking Neuroendocrine Tumor or Pancreatic Cancer

    PubMed Central

    Onda, Shinji; Okamoto, Tomoyoshi; Kanehira, Masaru; Fujioka, Shuichi; Harada, Tohru; Hano, Hiroshi; Fukunaga, Masaharu; Yanaga, Katsuhiko

    2012-01-01

    Autoimmune pancreatitis (AIP) can be difficult to distinguish from pancreatic cancer. We report a case of histopathologically proven AIP mimicking neuroendocrine tumor (NET) or pancreatic cancer in a 53-year-old man. He was referred to our hospital for further evaluation of a pancreatic mass detected on ultrasonography at a medical check-up. Abdominal ultrasonography showed a 15-mm hypoechoic mass located in the pancreatic body. Computed tomography revealed a tumor without any contrast enhancement, and magnetic resonance imaging demonstrated the mass to be hyperintense on diffusion-weighted image. Endoscopic retrograde cholangiopancreatography revealed slight dilatation of a branch of the pancreatic duct without stricture of the main pancreatic duct. The common bile duct seemed intact. Under suspicion of a non-functioning NET or malignant neoplasm, laparotomy was performed. At laparotomy, an elastic firm and well-circumscribed mass was found suggestive of a non-functioning NET, thus enucleation was performed. Histopathologically, the lesion corresponded to AIP. PMID:22423237

  19. 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

  20. Pancreatitis in cats.

    PubMed

    Armstrong, P Jane; Williams, David A

    2012-08-01

    Pancreatitis was considered a rare disease in the cat until a couple of decades ago when several retrospective studies of severe acute pancreatitis were published. It was apparent that few of the diagnostic tests of value in the dog were helpful in cats. With increasing clinical suspicion, availability of abdominal ultrasonography, and introduction of pancreas-specific blood tests of increasing utility, it is now accepted that acute pancreatitis is probably almost as common in cats as it is in dogs, although the etiology(s) remain more obscure. Pancreatitis in cats often co-exists with inflammatory bowel disease, less commonly with cholangitis, and sometimes with both. Additionally, pancreatitis may trigger hepatic lipidosis, while other diseases, such as diabetes mellitus, may be complicated by pancreatitis. Therapy is similar to that used in dogs, with added emphasis on early nutritional support to prevent hepatic lipidosis. Less is known about chronic pancreatitis than the acute form, but chronic pancreatitis is more common in cats than it is in dogs and may respond positively to treatment with corticosteroids.

  1. 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.

  2. Impaired beta-cell functions induced by chronic exposure of cultured human pancreatic islets to high glucose.

    PubMed

    Marshak, S; Leibowitz, G; Bertuzzi, F; Socci, C; Kaiser, N; Gross, D J; Cerasi, E; Melloul, D

    1999-06-01

    In type 2 diabetes, chronic hyperglycemia has been suggested to be detrimental to beta-cell function, causing reduced glucose-stimulated insulin secretion and disproportionately elevated proinsulin. In the present study, we investigated the effect on several beta-cell functions of prolonged in vitro exposure of human pancreatic islet cultures to high glucose concentrations. Islets exposed to high glucose levels (33 mmol/l) for 4 and 9 days showed dramatic decreases in glucose-induced insulin release and in islet insulin content, with increased proportion of proinsulin-like peptides relative to insulin. The depletion in insulin stores correlated with the reduction in insulin mRNA levels and human insulin promoter transcriptional activity. We also demonstrated that high glucose dramatically lowered the binding activity of pancreatic duodenal homeobox 1 (the glucose-sensitive transcription factor), whereas the transcription factor rat insulin promoter element 3b1 activator was less influenced and insulin enhancer factor 1 remained unaffected. Most of these beta-cell impairments were partially reversible when islets first incubated for 6 days in high glucose were transferred to normal glucose (5.5 mmol/l) concentrations for 3 days. We conclude that cultured human islets are sensitive to the deleterious effect of high glucose concentrations at multiple functional levels, and that such mechanisms may play an important role in the decreased insulin production and secretion of type 2 diabetic patients. PMID:10342809

  3. Small molecule kaempferol modulates PDX-1 protein expression and subsequently promotes pancreatic β-cell survival and function via CREB.

    PubMed

    Zhang, Yanling; Zhen, Wei; Maechler, Pierre; Liu, Dongmin

    2013-04-01

    Chronic hyperlipidemia causes β-cell apoptosis and dysfunction, thereby contributing to the pathogenesis of type 2 diabetes (T2D). Thus, searching for agents to promote pancreatic β-cell survival and improve its function could be a promising strategy to prevent and treat T2D. We investigated the effects of kaempferol, a small molecule isolated from ginkgo biloba, on apoptosis and function of β-cells and further determined the mechanism underlying its actions. Kaempferol treatment promoted viability, inhibited apoptosis and reduced caspase-3 activity in INS-1E cells and human islets chronically exposed to palmitate. In addition, kaempferol prevented the lipotoxicity-induced down-regulation of antiapoptotic proteins Akt and Bcl-2. The cytoprotective effects of kaempferol were associated with improved insulin secretion, synthesis, and pancreatic and duodenal homeobox-1 (PDX-1) expression. Chronic hyperlipidemia significantly diminished cyclic adenosine monophosphate (cAMP) production, protein kinase A (PKA) activation, cAMP-responsive element binding protein (CREB) phosphorylation and its regulated transcriptional activity in β-cells, all of which were restored by kaempferol treatment. Disruption of CREB expression by transfection of CREB siRNA in INS-1E cells or adenoviral transfer of dominant-negative forms of CREB in human islets ablated kaempferol protection of β-cell apoptosis and dysfunction caused by palmitate. Incubation of INS-1E cells or human islets with kaempferol for 48h induced PDX-1 expression. This effect of kaempferol on PDX-1 expression was not shared by a host of structurally related flavonoid compounds. PDX-1 gene knockdown reduced kaempferol-stimulated cAMP generation and CREB activation in INS-1E cells. These findings demonstrate that kaempferol is a novel survivor factor for pancreatic β-cells via up-regulating the PDX-1/cAMP/PKA/CREB signaling cascade.

  4. Review of idiopathic pancreatitis

    PubMed Central

    Lee, Jason Kihyuk; Enns, Robert

    2007-01-01

    Recent advances in understanding of pancreatitis and advances in technology have uncovered the veils of idiopathic pancreatitis to a point where a thorough history and judicious use of diagnostic techniques elucidate the cause in over 80% of cases. This review examines the multitude of etiologies of what were once labeled idiopathic pancreatitis and provides the current evidence on each. This review begins with a background review of the current epidemiology of idiopathic pancreatitis prior to discussion of various etiologies. Etiologies of medications, infections, toxins, autoimmune disorders, vascular causes, and anatomic and functional causes are explored in detail. We conclude with management of true idiopathic pancreatitis and a summary of the various etiologic agents. Throughout this review, areas of controversies are highlighted. PMID:18081217

  5. 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

  6. 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

  7. Laboratory testing for platelet function disorders.

    PubMed

    Israels, S J

    2015-05-01

    Platelet function testing is both complex and labor intensive. A stepwise approach to the evaluation of patients with suspected platelet disorders will optimize the use of laboratory resources, beginning with an appropriate clinical evaluation to determine whether the bleeding is consistent with a defect of primary hemostasis. Bleeding assessment tools, evaluation of platelet counts, and review of peripheral blood cell morphology can aid the initial assessment. For patients requiring further laboratory testing, platelet aggregometry, secretion assays, and von Willebrand factor assays are the most useful next steps and will direct further specialized testing including flow cytometry, electron microscopy, and molecular diagnostics. Guidelines and recommendations for standardizing platelet function testing, with a particular focus on light transmission aggregometry, are available and can provide a template for clinical laboratories in establishing procedures that will optimize diagnosis and assure quality results. This review outlines an approach to platelet function testing and reviews testing methods available to clinical laboratories.

  8. 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.

  9. Pancreatic functions in adolescents with beta thalassemia major could predict cardiac and hepatic iron loading: relation to T2-star (T2*) magnetic resonance imaging.

    PubMed

    Mokhtar, Galila M; Ibrahim, Wafaa E; Elbarbary, Nancy S; Matter, Randa M; Ibrahim, Ahmed S; Sayed, Safa M

    2016-03-01

    The aim of this study is to assess the correlation between cardiac and hepatic T2* MRI findings with the endocrine and exocrine pancreatic functions in known patients with β-thalassaemia major (β-TM). A total of 50 adolescent patients with β-TM and 44 healthy controls were investigated via: serum amylase, lipase, triglyceride index, oral glucose tolerance test and T2* MRI, to assess iron content in the heart and liver. Diabetes was found in 20%, and 40% of patients had impaired fasting glucose (IFG). Cardiac T2* was less than 10 ms in 22% indicating heavy load with iron in cardiac tissues. There was a significant decrease in median serum amylase (63.5 vs 87.5 IU/L, p=0.003) and lipase (63 vs 90 IU/L, p=0.017) among patients in comparison with the control group. Patients with β-TM and diabetes had lower serum amylase (32 vs 68 IU/L), lipase (28 vs 79 IU/L), cardiac and hepatic T2* MRI (7 vs 25.5 ms; 3 vs 6 ms, p<0.001 for all) than those without diabetes. Similar results were found among patients with IFG when compared with others (p<0.001 for all). Cardiac and hepatic T2* were inversely correlated to triglyceride index (r=-0.376, p=0.014 and r=-0.475, p=0.001, respectively) and positively correlated to amylase (r=0.791 and r=0.790) and lipase (r=0.784 and r=0.783; p<0.001 for all). The endocrine and exocrine pancreatic functions might become an equivalent predictor to cardiac and hepatic iron overload, especially in countries where MRI is not available or where it is expensive. The early occurrence of these abnormalities warrants more intensive chelation therapy.

  10. Childhood pancreatitis.

    PubMed

    Uretsky, G; Goldschmiedt, M; James, K

    1999-05-01

    Acute pancreatitis is a rare finding in childhood but probably more common than is generally realized. This condition should be considered in the evaluation of children with vomiting and abdominal pain, because it can cause significant morbidity and mortality. Clinical suspicion is required to make the diagnosis, especially when the serum amylase concentration is normal. Recurrent pancreatitis may be familial as a result of inherited biochemical or anatomic abnormalities. Patients with hereditary pancreatitis are at high risk for pancreatic cancer.

  11. 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

  12. 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.

  13. 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

  14. Transforming growth factor-beta/Smad3 signaling regulates insulin gene transcription and pancreatic islet beta-cell function.

    PubMed

    Lin, Huei-Min; Lee, Ji-Hyeon; Yadav, Hariom; Kamaraju, Anil K; Liu, Eric; Zhigang, Duan; Vieira, Anthony; Kim, Seong-Jin; Collins, Heather; Matschinsky, Franz; Harlan, David M; Roberts, Anita B; Rane, Sushil G

    2009-05-01

    Pancreatic islet beta-cell dysfunction is a signature feature of Type 2 diabetes pathogenesis. Consequently, knowledge of signals that regulate beta-cell function is of immense clinical relevance. Transforming growth factor (TGF)-beta signaling plays a critical role in pancreatic development although the role of this pathway in the adult pancreas is obscure. Here, we define an important role of the TGF-beta pathway in regulation of insulin gene transcription and beta-cell function. We identify insulin as a TGF-beta target gene and show that the TGF-beta signaling effector Smad3 occupies the insulin gene promoter and represses insulin gene transcription. In contrast, Smad3 small interfering RNAs relieve insulin transcriptional repression and enhance insulin levels. Transduction of adenoviral Smad3 into primary human and non-human primate islets suppresses insulin content, whereas, dominant-negative Smad3 enhances insulin levels. Consistent with this, Smad3-deficient mice exhibit moderate hyperinsulinemia and mild hypoglycemia. Moreover, Smad3 deficiency results in improved glucose tolerance and enhanced glucose-stimulated insulin secretion in vivo. In ex vivo perifusion assays, Smad3-deficient islets exhibit improved glucose-stimulated insulin release. Interestingly, Smad3-deficient islets harbor an activated insulin-receptor signaling pathway and TGF-beta signaling regulates expression of genes involved in beta-cell function. Together, these studies emphasize TGF-beta/Smad3 signaling as an important regulator of insulin gene transcription and beta-cell function and suggest that components of the TGF-beta signaling pathway may be dysregulated in diabetes.

  15. 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

    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

  16. PEDIATRIC PANCREATITIS

    PubMed Central

    Pohl, John F.; Uc, Aliye

    2015-01-01

    Purpose of Review The purpose of this review is to describe recent developments in pediatric pancreatitis and to discuss etiologies and current management. Recent Findings Although recent studies have estimated the annual incidence of pediatric acute pancreatitis approaching that of adults, there are no established guidelines about its diagnosis and treatment in children. Genetic and structural/congenital abnormalities are emerging as the primary risk factors for pediatric acute recurrent and chronic pancreatitis. Specifically, chronic pancreatitis is associated with a significant socioeconomic burden in children. Both medical and surgical therapies are proposed for pediatric chronic pancreatitis, but there is little evidence that they are beneficial. Summary Acute, acute recurrent and chronic pancreatitis create significant health issues in the pediatric population. Medical and surgical therapies exist to potentially treat these conditions, but the pediatric data is limited and the cohorts are small. A multidisciplinary and multicenter approach is necessary to better determine pancreatic disease processes and treatment options in children. PMID:26181572

  17. 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

  18. CIT photoheliograph functional verification unit test program

    NASA Technical Reports Server (NTRS)

    1973-01-01

    Tests of the 2/3-meter photoheliograph functional verification unit FVU were performed with the FVU installed in its Big Bear Solar Observatory vacuum chamber. Interferometric tests were run both in Newtonian (f/3.85) and Gregorian (f/50) configurations. Tests were run in both configurations with optical axis horizontal, vertical, and at 45 deg to attempt to determine any gravity effects on the system. Gravity effects, if present, were masked by scatter in the data associated with the system wavefront error of 0.16 lambda rms ( = 6328A) apparently due to problems in the primary mirror. Tests showed that the redesigned secondary mirror assembly works well.

  19. 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

  20. 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

  1. 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.

  2. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    ClinicalTrials.gov

    2016-09-14

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  3. Functional testing: Approaches and injury management integration.

    PubMed

    Johnson, Laurie J.; Miller, Margot

    2001-01-01

    Functional Capacity Evaluations (FCEs) have become the standard for identifying an individual's physical abilities and/or limitations following injury or illness. While philosophies and approaches differ, the focus of most FCE systems is to identify the individual's maximum capabilities. This article will discuss the usefulness of the FCE information and how FCEs are impacted by multiple factors including APTA guidelines, machine based testing, therapist expertise, medical legal credibility and court testimony, IMEs and FCE, and return to work/return to function.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. Chronic pancreatitis.

    PubMed

    Chari, S T; DiMagno, E P

    2001-09-01

    An increasing number of novel mutations are associated with chronic pancreatitis. Some cause a high-penetrance, autosomal dominant type of clinical picture (eg, mutations at codons 29 and 122 of the cationic trypsinogen gene), whereas others have a low penetrance or are frequent in the general population (eg, mutations in Kazal type 1 [SPINK1] and in codons 16, 22, and 23 of the cationic trypsinogen gene) and act as disease modifiers. The results of recent studies indicate that smoking adversely affects the course and complications of chronic pancreatitis (more frequent and faster rate of calcification and higher risk of development of pancreatic cancer). Thus, regardless of the cause of chronic pancreatis, patients with this condition should not smoke. Using current diagnostic criteria, the accuracy of endoscopic ultrasound for the diagnosis of chronic pancreatitis is not good. For example, 39% of dyspeptic persons without any other evidence of chronic pancreatitis fulfilled the endoscopic ultrasound criteria for chronic pancreatitis. Diabetes frequently occurs in chronic pancreatitis, but it is not prevented or increased by pancreatic surgery. Islet cell autotransplantation holds promise for the prevention of diabetes in patients requiring total pancreatectomy if the pancreas is not extensively fibrotic. Splenic vein occlusion is present in 7% of patients undergoing surgery for chronic pancreatitis, but fewer than one fifth of these patients have variceal bleeding before or after surgery.

  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. Pathophysiology of alcoholic pancreatitis: An overview

    PubMed Central

    Chowdhury, Parimal; Gupta, Priya

    2006-01-01

    Use of alcohol is a worldwide habit regardless of socio-economic background. Heavy alcohol consumption is a potential risk factor for induction of pancreatitis. The current review cites the updated literature on the alcohol metabolism, its effects on gastrointestinal and pancreatic function and in causing pancreatic injury, genetic predisposition of alcohol induced pancreatitis. Reports describing prospective mechanisms of action of alcohol activating the signal transduction pathways, induction of oxidative stress parameters through the development of animal models are being presented. PMID:17167828

  11. The quest to make fully functional human pancreatic beta cells from embryonic stem cells: climbing a mountain in the clouds.

    PubMed

    Johnson, James D

    2016-10-01

    The production of fully functional insulin-secreting cells to treat diabetes is a major goal of regenerative medicine. In this article, I review progress towards this goal over the last 15 years from the perspective of a beta cell biologist. I describe the current state-of-the-art, and speculate on the general approaches that will be required to identify and achieve our ultimate goal of producing functional beta cells. The need for deeper phenotyping of heterogeneous cultures of stem cell derived islet-like cells in parallel with a better understanding of the heterogeneity of the target cell type(s) is emphasised. This deep phenotyping should include high-throughput single-cell analysis, as well as comprehensive 'omics technologies to provide unbiased characterisation of cell products and human beta cells. There are justified calls for more detailed and well-powered studies of primary human pancreatic beta cell physiology, and I propose online databases of standardised human beta cell responses to physiological stimuli, including both functional and metabolomic/proteomic/transcriptomic profiles. With a concerted, community-wide effort, including both basic and applied scientists, beta cell replacement will become a clinical reality for patients with diabetes. PMID:27473069

  12. The quest to make fully functional human pancreatic beta cells from embryonic stem cells: climbing a mountain in the clouds.

    PubMed

    Johnson, James D

    2016-10-01

    The production of fully functional insulin-secreting cells to treat diabetes is a major goal of regenerative medicine. In this article, I review progress towards this goal over the last 15 years from the perspective of a beta cell biologist. I describe the current state-of-the-art, and speculate on the general approaches that will be required to identify and achieve our ultimate goal of producing functional beta cells. The need for deeper phenotyping of heterogeneous cultures of stem cell derived islet-like cells in parallel with a better understanding of the heterogeneity of the target cell type(s) is emphasised. This deep phenotyping should include high-throughput single-cell analysis, as well as comprehensive 'omics technologies to provide unbiased characterisation of cell products and human beta cells. There are justified calls for more detailed and well-powered studies of primary human pancreatic beta cell physiology, and I propose online databases of standardised human beta cell responses to physiological stimuli, including both functional and metabolomic/proteomic/transcriptomic profiles. With a concerted, community-wide effort, including both basic and applied scientists, beta cell replacement will become a clinical reality for patients with diabetes.

  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. 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

  15. A new scintigraphic test of neorectal function

    SciTech Connect

    O'Connell, P.R.; Omdahl, A.L.; Brown, M.L.; Kelly, K.A.

    1985-05-01

    Current tests of neorectal function after colectomy, mucosal rectectomy and ileal pouch-anal anastomosis are inadequate. The authors developed a new scintigraphic test that uses an artificial stool made of aluminium magnesium silicate gel (Veegum). Solutions of the gel were labeled with 1 mCi Tc-99m by stirring Veegum powder into water containing the isotope at 37/sup 0/C. Excellent binding was obtained with the sulfur colloid form of the isotope compared with the pertechnetate or ovalbumin forms (Table). The sulfur colloid isotope in 7.5% gel was used in subsequent tests. The volume given to the patients corresponded to the maximum capacity of the ileal pouch as measured manometrically; it averaged 300 ml. Ten patients have been studied to date with minimal patient discomfort. The gel was introduced over a 2 minute period via a 16Fr. transanal tube with the patient in the left lateral position. After 5 minutes AP standing and R lateral scans were taken. Then a dynamic scan was taken while the patient evacuated the gel into a commode. After evacuation AP and R lateral scans were repeated. Computer analysis was used to determine both the functional pouch capacity and the rates of emptying of the pouch and the more proximal ileum. The test has proven useful in the assessment of neorectal anatomy and function after ileal pouch-anal anastomosis.

  16. Inhibition of Small Maf Function in Pancreatic β-Cells Improves Glucose Tolerance Through the Enhancement of Insulin Gene Transcription and Insulin Secretion.

    PubMed

    Nomoto, Hiroshi; Kondo, Takuma; Miyoshi, Hideaki; Nakamura, Akinobu; Hida, Yoko; Yamashita, Ken-ichiro; Sharma, Arun J; Atsumi, Tatsuya

    2015-10-01

    The large-Maf transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) has been found to be crucial for insulin transcription and synthesis and for pancreatic β-cell function and maturation. However, insights about the effects of small Maf factors on β-cells are limited. Our goal was to elucidate the function of small-Maf factors on β-cells using an animal model of endogenous small-Maf dysfunction. Transgenic (Tg) mice with β-cell-specific expression of dominant-negative MafK (DN-MafK) experiments, which can suppress the function of all endogenous small-Mafs, were fed a high-fat diet, and their in vivo phenotypes were evaluated. Phenotypic analysis, glucose tolerance tests, morphologic examination of β-cells, and islet experiments were performed. DN-MafK-expressed MIN6 cells were also used for in vitro analysis. The results showed that DN-MafK expression inhibited endogenous small-Maf binding to insulin promoter while increasing MafA binding. DN-MafK Tg mice under high-fat diet conditions showed improved glucose metabolism compared with control mice via incremental insulin secretion, without causing changes in insulin sensitivity or MafA expression. Moreover, up-regulation of insulin and glucokinase gene expression was observed both in vivo and in vitro under DN-MafK expression. We concluded that endogenous small-Maf factors negatively regulates β-cell function by competing for MafA binding, and thus, the inhibition of small-Maf activity can improve β-cell function. PMID:25763640

  17. 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.

  18. 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

  19. Gamow states as continuous linear functionals over analytical test functions

    SciTech Connect

    Bollini, C.G.; Civitarese, O.; De Paoli, A.L.; Rocca, M.C. |

    1996-09-01

    The space of analytical test functions {xi}, rapidly decreasing on the real axis (i.e., Schwartz test functions of the type S on the real axis), is used to construct the rigged Hilbert space (RHS) ({xi},H,{xi}{prime}). Gamow states (GS) can be defined in RHS starting from Dirac{close_quote}s formula. It is shown that the expectation value of a self-adjoint operator acting on a GS is real. We have computed exactly the probability of finding a system in a GS and found that it is finite. The validity of recently proposed approximations to calculate the expectation value of self-adjoint operators in a GS is discussed. {copyright} {ital 1996 American Institute of Physics.}

  20. 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

  1. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez-Muñoz, J Enrique

    2013-10-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern knowledge of the etiopathogenesis of the disease, the pharmacological treatment of pain, and knowledge of the natural history of autoimmune pancreatitis. New evidence supports the relatively low prevalence of chronic alcoholic pancreatitis, and the role of tobacco in triggering the etiopathogenic mechanisms of chronic pancreatitis is better understood. Some studies have identified certain factors that are associated with having a positive genetic test in adults with chronic idiopathic pancreatitis, which should help to select those patients who should undergo genetic studies. Antioxidant therapy has been shown to be effective in reducing pain secondary to chronic pancreatitis, although the type and optimal dose of antioxidants remains to be elucidated. Finally, the development of exocrine and endocrine pancreatic insufficiency is a very common finding during the long-term follow-up of patients with autoimmune pancreatitis. Smoking also seems to play a role in this type of pancreatitis.

  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. [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

  4. The Inactivation of Arx in Pancreatic α-Cells Triggers Their Neogenesis and Conversion into Functional β-Like Cells

    PubMed Central

    Courtney, Monica; Gjernes, Elisabet; Druelle, Noémie; Ravaud, Christophe; Vieira, Andhira; Ben-Othman, Nouha; Pfeifer, Anja; Avolio, Fabio; Leuckx, Gunter; Lacas-Gervais, Sandra; Burel-Vandenbos, Fanny; Ambrosetti, Damien; Hecksher-Sorensen, Jacob; Ravassard, Philippe; Heimberg, Harry; Mansouri, Ahmed; Collombat, Patrick

    2013-01-01

    Recently, it was demonstrated that pancreatic new-born glucagon-producing cells can regenerate and convert into insulin-producing β-like cells through the ectopic expression of a single gene, Pax4. Here, combining conditional loss-of-function and lineage tracing approaches, we show that the selective inhibition of the Arx gene in α-cells is sufficient to promote the conversion of adult α-cells into β-like cells at any age. Interestingly, this conversion induces the continuous mobilization of duct-lining precursor cells to adopt an endocrine cell fate, the glucagon+ cells thereby generated being subsequently converted into β-like cells upon Arx inhibition. Of interest, through the generation and analysis of Arx and Pax4 conditional double-mutants, we provide evidence that Pax4 is dispensable for these regeneration processes, indicating that Arx represents the main trigger of α-cell-mediated β-like cell neogenesis. Importantly, the loss of Arx in α-cells is sufficient to regenerate a functional β-cell mass and thereby reverse diabetes following toxin-induced β-cell depletion. Our data therefore suggest that strategies aiming at inhibiting the expression of Arx, or its molecular targets/co-factors, may pave new avenues for the treatment of diabetes. PMID:24204325

  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.

  6. 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

  7. 33 CFR 157.12f - Workshop functional test requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Workshop functional test... CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12f Workshop functional test requirements... functional test on a suitable test bench prior to delivery. The detailed program for a functional test...

  8. 33 CFR 157.12f - Workshop functional test requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Workshop functional test... CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12f Workshop functional test requirements... functional test on a suitable test bench prior to delivery. The detailed program for a functional test...

  9. 33 CFR 157.12f - Workshop functional test requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Workshop functional test... CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12f Workshop functional test requirements... functional test on a suitable test bench prior to delivery. The detailed program for a functional test...

  10. Type 1 autoimmune pancreatitis.

    PubMed

    Zen, Yoh; Bogdanos, Dimitrios P; Kawa, Shigeyuki

    2011-12-07

    Before the concept of autoimmune pancreatitis (AIP) was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP) has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney) and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of regulatory T-cells are assumed

  11. Analysis of morphological and functional maturation of neoislets generated in vitro from pancreatic ductal cells and their suitability for islet banking and transplantation.

    PubMed

    Katdare, M R; Bhonde, R R; Parab, P B

    2004-07-01

    The pancreatic ductal stem cells are known to differentiate into islets of Langerhans; however, their yield is limited and the islet population is not defined. Therefore, the aims of the present study were to improvise a methodology for obtaining large numbers of islets in vitro and to characterize their morphological and functional status for islet cell banking and transplantation. Pancreatic ductal epithelial cell cultures were set in serum-free medium. Monolayers of epithelial cells in culture gave rise to islet-like clusters within 3-4 weeks. The identity of neoislets was confirmed by dithizone staining and analysis of the gene expression for endocrine markers by reverse transcriptase-polymerase chain reaction (RT-PCR). The islet population obtained was analysed by image analysis and insulin secretion in response to secretagogues. The cellular extracts from neoislets were immunoreactive to anti-insulin antibody and expressed insulin, glucagon, GLUT-2, PDX-1 and Reg-1 genes. The islets generated within 3-4 weeks exhibited a mixed population of large- and small-sized islets with clear cut dichotomy in the pattern of their insulin secretion in response to L-arginine and glucose. These neoislets maintained their structural and functional integrity on cryopreservation and transplantation indicating their suitability for islet cell banking. Thus, the present study describes an improved method for obtaining a constant supply of large numbers of islets from pancreatic ductal stem cell cultures. The newly generated islets undergo functional maturation indicating their suitability for transplantation.

  12. 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

  13. Molecular cloning and functional characterization of the oxytocin receptor from a rat pancreatic cell line (RINm5F).

    PubMed

    Jeng, Y J; Lolait, S J; Strakova, Z; Chen, C; Copland, J A; Mellman, D; Hellmich, M R; Soloff, M S

    1996-12-01

    Oxytocin (OT) and vasopressin (AVP) stimulate insulin and glucagon release from the pancreas, and evoke insulin secretion from the rat insulinoma cell line, RINm5F. To determine which AVP/OT receptor subtype is expressed in RINm5F cells, we used PCR with degenerate primers to two transmembrane domains of the AVP (V1a, V1b (or V3), V2) and OT receptors (OTRs). The single PCR fragment identified was used to obtain a full length cDNA from a RINm5F cDNA library. Comparison of the deduced amino acid sequence of this clone with uterine OTR sequences from several species (human, sheep, bovine) and to the pig kidney epithelial cell (LLC-PK1) OTR reveals a very high degree of homology. After the RIN cell OTR cDNA was stably transfected into CHO cells (CHO-OTR), the cell membranes bound iodinated oxytocin antagonist with an apparent Kd comparable to that of RIN cell membranes and those from other OT target cells. Comparison of the ligand specificities of CHO-OTR and RIN cells membranes showed that the relative Ki values of a series of OT analogues were approximately equivalent in both preparations. The rank order of apparent Ki values also corresponded to published values for the rat myometrium, where OT elicits intracellular calcium transients, and increases inositol phosphate production. In uterin endometrium and amnion cells, OT stimulates prostaglandin release. Stimulation of CHO-OTR cells with OT caused an increase in cytosolic calcium concentration originating from both intracellular and extracellular sources, and a dose-dependent increase in inositol phosphate levels. Arachidonic acid release and PGE2 synthesis were also stimulated by OT. These findings (amino acid sequence homology, binding specificity, and signal transduction/second messenger production) suggest that OTRs from RINm5F cells are indistinguishable from OTRs that have been described in other tissues. The expression of OTR in pancreatic cells implies that OT plays a role in pancreatic function.

  14. 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.

  15. Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL.

    PubMed

    Plaisance, Valérie; Brajkovic, Saška; Tenenbaum, Mathie; Favre, Dimitri; Ezanno, Hélène; Bonnefond, Amélie; Bonner, Caroline; Gmyr, Valéry; Kerr-Conte, Julie; Gauthier, Benoit R; Widmann, Christian; Waeber, Gérard; Pattou, François; Froguel, Philippe; Abderrahmani, Amar

    2016-01-01

    Elevated plasma concentration of the pro-atherogenic oxidized low density lipoprotein cholesterol (LDL) triggers adverse effects in pancreatic beta-cells and is associated with type 2 diabetes. Here, we investigated whether the endoplasmic reticulum (ER) stress is a key player coupling oxidative stress to beta-cell dysfunction and death elicited by human oxidized LDL. We found that human oxidized LDL activates ER stress as evidenced by the activation of the inositol requiring 1α, and the elevated expression of both DDIT3 (also called CHOP) and DNAJC3 (also called P58IPK) ER stress markers in isolated human islets and the mouse insulin secreting MIN6 cells. Silencing of Chop and inhibition of ER stress markers by the chemical chaperone phenyl butyric acid (PBA) prevented cell death caused by oxidized LDL. Finally, we found that oxidative stress accounts for activation of ER stress markers induced by oxidized LDL. Induction of Chop/CHOP and p58IPK/P58IPK by oxidized LDL was mimicked by hydrogen peroxide and was blocked by co-treatment with the N-acetylcystein antioxidant. As a conclusion, the harmful effects of oxidized LDL in beta-cells requires ER stress activation in a manner that involves oxidative stress. This mechanism may account for impaired beta-cell function in diabetes and can be reversed by antioxidant treatment. PMID:27636901

  16. Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL

    PubMed Central

    Favre, Dimitri; Ezanno, Hélène; Bonnefond, Amélie; Bonner, Caroline; Gmyr, Valéry; Kerr-Conte, Julie; Gauthier, Benoit R.; Widmann, Christian; Waeber, Gérard; Pattou, François; Froguel, Philippe; Abderrahmani, Amar

    2016-01-01

    Elevated plasma concentration of the pro-atherogenic oxidized low density lipoprotein cholesterol (LDL) triggers adverse effects in pancreatic beta-cells and is associated with type 2 diabetes. Here, we investigated whether the endoplasmic reticulum (ER) stress is a key player coupling oxidative stress to beta-cell dysfunction and death elicited by human oxidized LDL. We found that human oxidized LDL activates ER stress as evidenced by the activation of the inositol requiring 1α, and the elevated expression of both DDIT3 (also called CHOP) and DNAJC3 (also called P58IPK) ER stress markers in isolated human islets and the mouse insulin secreting MIN6 cells. Silencing of Chop and inhibition of ER stress markers by the chemical chaperone phenyl butyric acid (PBA) prevented cell death caused by oxidized LDL. Finally, we found that oxidative stress accounts for activation of ER stress markers induced by oxidized LDL. Induction of Chop/CHOP and p58IPK/P58IPK by oxidized LDL was mimicked by hydrogen peroxide and was blocked by co-treatment with the N-acetylcystein antioxidant. As a conclusion, the harmful effects of oxidized LDL in beta-cells requires ER stress activation in a manner that involves oxidative stress. This mechanism may account for impaired beta-cell function in diabetes and can be reversed by antioxidant treatment. PMID:27636901

  17. Pathophysiology of autoimmune pancreatitis

    PubMed Central

    Pezzilli, Raffaele; Pagano, Nico

    2014-01-01

    Autoimmune pancreatitis (AIP) is a recently discovered form of pancreatitis and represents one of the diseases of the pancreas which can be cured and healed medically. International consensus diagnostic criteria have been developed, and the clinical phenotypes associated with the histopathologic patterns of lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis should be referred to as type 1 and type 2 AIP, respectively. Most importantly, in type 1 AIP, the pancreatic manifestations are associated with other extrapancreatic disorders, resembling an immunoglobulin G4 (IgG4)-related disease. In addition, the pancreas of a patient with AIP is often infiltrated by various types of immune cells; the cluster of differentiation (CD) 4 or CD8 T lymphocytes and IgG4-bearing plasma cells have been found in the pancreatic parenchyma and other involved organs in AIP and factors regulating T-cell function may influence the development of AIP. From a genetic point of view, it has also been reported that DRB1*0405 and DQB1*0401 mutations are significantly more frequent in patients with AIP when compared to those with chronic calcifying pancreatitis, and that only DQB1*0302 had a significant association with the relapse of AIP. Finally, it has been found that the polymorphic genes encoding cytotoxic T lymphocyte-associated antigen 4, a key negative regulator of the T-cell immune response, are associated with AIP in a Chinese population. Even if these data are not concordant, it is possible that physiological IgG4 responses are induced by prolonged antigen exposure and controlled by type 2 helper T cells. We reviewed the current concepts regarding the pathophysiology of this intriguing disease, focusing on the importance of the humoral and cellular immune responses. PMID:24891971

  18. Endoscopic sphincterotomy in acute biliary pancreatitis: A question of anesthesiological risk

    PubMed Central

    Pezzilli, Raffaele

    2009-01-01

    Two consecutive surveys of acute pancreatitis in Italy, based on more than 1000 patients with acute pancreatitis, reported that the etiology of the disease indicates biliary origin in about 60% of the cases. The United Kingdom guidelines report that severe gallstone pancreatitis in the presence of increasingly deranged liver function tests and signs of cholangitis (fever, rigors, and positive blood cultures) requires an immediate and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). These guidelines also recommend that patients with gallstone pancreatitis should undergo prompt cholecystectomy, possibly during the same hospitalization. However, a certain percentage of patients are unfit for cholecystectomy because advanced age and presence of comorbidity. We evaluated the early and long-term results of endoscopic intervention in relation to the anesthesiological risk for 87 patients with acute biliary pancreatitis. All patients underwent ERCP and were evaluated according to the American Society of Anesthesiology (ASA) criteria immediately before the operative procedure. The severity of acute pancreatitis was positively related to the anesthesiological grade. There was no significant relationship between the frequency of biliopancreatic complications during the follow-up and the ASA grade. The frequency of cholecystectomy was inversely related to the ASA grade and multivariate analysis showed that the ASA grade and age were significantly related to survival. Finally, endoscopic treatment also appeared to be safe and effective in patients at high anesthesiological risk with acute pancreatitis. These results further support the hypothesis that endoscopic sphincterotomy might be considered a definitive treatment for patients with acute biliary pancreatitis and an elevated ASA grade. PMID:21160646

  19. 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

  20. [Endoscopic therapy of acute and chronic pancreatitis].

    PubMed

    Veltzke-Schlieker, W; Adler, A; Abou-Rebyeh, H; Wiedenmann, B; Rösch, T

    2005-02-01

    Endoscopic therapy is valuable for both acute and chronic pancreatitis. Early endoscopic papillotomy appears, in the case of a severe course of acute biliary pancreatitis, to be advantageous. Endoscopic drainage can be considered in cases of acute fluid retention and necrosis as well as subacute, non-healing pancreatitis or cyst development. By acute chronic pancreatitis with strictures or bile duct stones, papillotomy, dilation and stent insertion can lead to an improvement in pain symptoms. An improvement in endo- or exocrine function, however, is not expected. Studies on the endoscopic therapy of pancreatitis are still very limited, and recommendations can usually only be made based on retrospective case series. PMID:15657718

  1. 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.

  2. 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

  3. Pancreatic abscess.

    PubMed Central

    Gartell, P C

    1982-01-01

    Three cases of pancreatic abscess are described to show the difficulties in diagnosis and that inadequate treatment is invariably fatal. Early recognition and prompt surgical drainage, together with biliary decompression if indicated, are advised. PMID:7069670

  4. 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

  5. [Tomodensitometry of severe acute pancreatitis].

    PubMed

    Frija, J; Abanou, A; Viandier, A; Laval-Jeantet, M

    1983-01-01

    90 computed tomographic examinations were performed to 57 patients referred at Hospital Saint-Louis for an acute pancreatitis. 32 patients were operated or autopsied. Among these 32 patients, 19 patients had 21 examinations before surgery or autopsy; the other 13 patients had their computed tomographic examinations after one or more surgical procedures. During a severe acute pancreatitis the pancreas is always large either locally or diffusely. A pancreatic reaction is visible around and possibly at distance of the pancreas. When extraluminal gas is visible (3/5) it signifies gangrenous pancreatitis but it is necessary to eliminate a digestive fistulous tract and/or a communication between a pseudocyst and the digestive tract. Except gangrenous it is not possible to precise the nature of pancreatic reaction. The diagnosis of pseudocyst was easy 9/10, difficult 1/10; we did a false positive diagnosis of pseudocyst. Computed tomography and ultrasounds were compared in ten patients for the search of gallbladder lithiasis. Computed tomography can show large and small (2/4) biliary calculus in the gallbladder that cannot be shown by ultrasounds. A normal pancreas in a normal retroperitoneal space exclude the diagnosis of a severe acute pancreatitis. CT aspects of acute pancreatitis must be considered as a good diagnostic test of an acute pancreatitis.

  6. Pancreatic Cancer Cell Glycosylation Regulates Cell Adhesion and Invasion through the Modulation of α2β1 Integrin and E-Cadherin Function

    PubMed Central

    Bassagañas, Sònia; Carvalho, Sandra; Dias, Ana M.; Pérez-Garay, Marta; Ortiz, M. Rosa; Figueras, Joan; Reis, Celso A.; Pinho, Salomé S.; Peracaula, Rosa

    2014-01-01

    In our previous studies we have described that ST3Gal III transfected pancreatic adenocarcinoma Capan-1 and MDAPanc-28 cells show increased membrane expression levels of sialyl-Lewis x (SLex) along with a concomitant decrease in α2,6-sialic acid compared to control cells. Here we have addressed the role of this glycosylation pattern in the functional properties of two glycoproteins involved in the processes of cancer cell invasion and migration, α2β1 integrin, the main receptor for type 1 collagen, and E-cadherin, responsible for cell-cell contacts and whose deregulation determines cell invasive capabilities. Our results demonstrate that ST3Gal III transfectants showed reduced cell-cell aggregation and increased invasive capacities. ST3Gal III transfected Capan-1 cells exhibited higher SLex and lower α2,6-sialic acid content on the glycans of their α2β1 integrin molecules. As a consequence, higher phosphorylation of focal adhesion kinase tyrosine 397, which is recognized as one of the first steps of integrin-derived signaling pathways, was observed in these cells upon adhesion to type 1 collagen. This molecular mechanism underlies the increased migration through collagen of these cells. In addition, the pancreatic adenocarcinoma cell lines as well as human pancreatic tumor tissues showed colocalization of SLex and E-cadherin, which was higher in the ST3Gal III transfectants. In conclusion, changes in the sialylation pattern of α2β1 integrin and E-cadherin appear to influence the functional role of these two glycoproteins supporting the role of these glycans as an underlying mechanism regulating pancreatic cancer cell adhesion and invasion. PMID:24878505

  7. Microarray-based gene expression profiling reveals genes and pathways involved in the oncogenic function of REG3A on pancreatic cancer cells.

    PubMed

    Xu, Qianqian; Fu, Rong; Yin, Guoxiao; Liu, Xiulan; Liu, Yang; Xiang, Ming

    2016-03-10

    We previously reported that regenerating islet-derived protein 3 alpha (REG3A) exacerbates pancreatic malignancies. The mechanism of this effect has not been clearly elucidated. Here we first identified key differentially expressed genes (DEGs) and signal pathways in the pancreatic cancer cell line SW1990, compared to two control cell lines, by microarray analysis. We then identified key genes and pathways regulated by REG3A or the cytokine IL6 in SW1990 cells. Afterwards, these DEGs induced by REG3A or IL6 were subjected to KEGG pathway enrichment analysis and GO function analysis by the DAVID online tool. Ultimately, we constructed protein-protein interaction networks among the DEGs by Cytoscape. Among the three pancreatic cell lines, SW1990 exhibited highly deterioration with the activation of genes and pathways related to proliferation, survival, angiogenesis, and invasion. As a result, 50 DEGs enriched in 11 pathways were identified in REG3A-treated SW1990 cells, and 28 DEGs enriched in 9 pathways were detected in IL6-treated cells. Overall, results of microarray analysis followed by qRT-PCR and Western blotting suggest that REG3A regulates pancreatic cell growth by increasing the expression of at least 8 genes: JAK1, STAT3, IL10, FOXM1, KRAS, MYC, CyclinD1, and c-fos; and activation of at least 4 signal pathways: TGFβ, PDGF, angiogenesis and RAS. Similar results were obtained with IL6 treatment. Regulation network analysis confirmed the cell growth related DEGs, and further uncovered three transcription factor families with immune functions regulated by REG3A.

  8. Chronic pancreatitis and pancreatic cancer.

    PubMed

    Maisonneuve, Patrick; Lowenfels, Albert B

    2002-01-01

    Pancreatic cancer is the fourth leading cause of cancer deaths in the USA in both sexes. Early diagnosis is difficult and the overall mortality rate is high. Individuals at high risk for pancreatic cancer include smokers, and persons with all forms of chronic alcoholic, metabolic, tropical or hereditary pancreatitis. The duration of exposure to inflammation seems to be the major factor involved in the transition from benign to malignant condition. Smoking, which appears to further accelerate the carcinogenic transformation, remains the strongest risk factor amenable to preventive intervention.

  9. 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.

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

    PubMed

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

    2015-08-01

    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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. Unexpected fetal demise despite the reactive nonstress test during the conservative management of acute pancreatitis in pregnancy

    PubMed Central

    Avsar, Ayse Filiz; Yildirim, Melahat; Cinkaya, Aysegul

    2014-01-01

    INTRODUCTION Dealing with acute pancreatitis in pregnancy is a challenging problem due to unexpected nature of the disease. PRESENTATION OF CASE We report a complicated case of a 29-year-old pregnant woman with a mild acute pancreatitis whose pregnancy ended up with an unexpected fetal demise at her 34th gestational week. This unfortunate outcome led us reconsider our obstetrical approach to acute pancreatitis during pregnancy. CONCLUSION Based on this unfortunate event, we now think that obstetricians should keep in mind that even in the presence of reassuring NST and biophysical profile assessment, an unpredictable fetal loss can occur during the medical management of the pregnancies complicated with mild acute pancreatitis. DISCUSSION The subject patient of this case report was diagnosed with mild AP and underwent conservative medical management. Since the patient was stable and fetal well-being was confirmed with BPP and NST, the termination of pregnancy was out of question at that time. The occurrence of unexpected fetal death despite assuring parameters led us reconsider the approach to the pregnant women with mild AP. PMID:25460471

  19. Segmental pancreatic autotransplantation for chronic pancreatitis. A preliminary report

    SciTech Connect

    Rossi, R.L.; Braasch, J.W.; O'Bryan, E.M.; Watkins, E. Jr.

    1983-03-01

    A patient who underwent 95% pancreatectomy with autotransplantation of the body and tail of the gland to the femoral area for chronic pancreatitis is presented. The pain resolved, and the patient's blood glucose level remained within normal limits. High levels of insulin were found in the iliac vein on the transplanted side. Patency of the graft was demonstrated by technetium scan and arteriography and followed by a color-coded Doppler imaging system. Segmental pancreatic autotransplantation offers a method of relieving pain with preservation of endocrine function in selected patients with chronic pancreatitis.

  20. Platelet Function Testing-Guided Antiplatelet Therapy

    PubMed Central

    Spannagl, Michael

    2013-01-01

    Cardiovascular diseases are the leading cause of death in the Western world. Several factors have led to the increase in vascular disorders, including the aging population, unhealthy lifestyles, increasing rates of diabetes and raised lipids, and further risk factors resulting in inflammation and calcification of the vascular endothelium. Activated platelets in damaged blood vessels can trigger arterial thrombus formation, leading to vascular occlusion with subsequent organ hypoperfusion and clinical manifestation of myocardial infarction, stroke, or peripheral artery disease. Platelet inhibitors such as aspirin and clopidogrel (Plavix® and generics) are prescribed as primary or secondary prevention to attenuate chronic platelet activation. However, a significant proportion of patients do not respond adequately to uniform antiplatelet treatment. These ‘non-responders’ have an increased risk for stent thrombosis, stroke, and other ischemic complications. Platelet function (PF) tests can identify these patients thus enabling physicians to offer personalized and alternative treatment strategies. Recent alternatives to clopidogrel include prasugrel (Efient®) and ticagrelor (Brilique®) – that are both more potent than clopidogrel but also more expensive and associated with a higher risk of bleeding complications. Given these drawbacks, PF testing might help clinicians to prescribe optimal antiplatelet agent to maximize patient safety and efficacy while minimizing costs. While randomized studies using different test systems have left clinicians puzzled about the medical value of tailored antiplatelet therapy, accumulated evidence from recent studies on tailored antiplatelet therapies and the association with improved outcomes have now resulted in a consensus expert opinion for the specific adoption of PF diagnostics into clinical practice.

  1. Effects of intensive insulin therapy upon pancreatic β cell function in patients newly diagnosed with type II diabetes

    PubMed Central

    Wang, Defeng; Sun, Li; Song, Guangyao; Chen, Shuchun

    2015-01-01

    Objective: This study was designed to evaluate the clinical efficacy of intensive insulin therapy for patients newly diagnosed with type 2 diabetes. Methods: A total of 219 patients newly diagnosed with type 2 diabetes were randomly assigned into insulin group (n = 55), gliclazide group (n = 52), metformin group (n = 55) and pioglitazone group (n = 57). On the basis of diet and physical interventions, patients in the insulin group received intensive insulin therapy. Those in other three groups were given oral intake of medication. All treatment schemes endured for 12 weeks. A variety of indexes including fasting blood-glucose (FPG), FPG at 2 h after diet (FPG 2 h), hemoglobin A1 c (HbAlc), area under the curve (AUC) for insulin (insulin AUC) after glucose load, C-peptide AUC after glucose load (C-peptide AUC), changes in insulin secretion index (Homa-β) and insulin resistance index( Homa-IR) were accurately measured and statistically among different groups. Results: The insulin AUC at 0-30 min, C-peptide AUC at 0-30 min and Homa-β in the insulin group were equally significantly higher compared with those levels in the other three groups. In addition, the level of Homa-IR in the insulin, metformin and pioglitazone groups were all significantly reduced compared with the values prior to respective treatment (all P < 0.05). Conclusion: Compared with oral administration of hypoglycemic drugs, intensive insulin therapy is able to better improve pancreatic β cell function and insulin resistance for newly-diagnosed type 2 diabetes patients. PMID:25785143

  2. 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

  3. 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.

  4. Functional expression and analysis of the pancreatic transcription factor PDX-1 in yeast.

    PubMed

    Ozcan, Sabire; Mosley, Amber L; Aryal, Bishwa K

    2002-07-19

    The pancreas-specific transcription factor Pdx-1 is important for pancreas development and beta-cell specific gene expression in insulin-producing cells. We have expressed the mouse PDX-1 gene in the yeast Saccharomyces cerevisiae and characterized its functional domains. Pdx-1 functions as a strong activator in yeast and stimulates gene expression by more than 80-fold. The transcriptional activation domain of Pdx-1 is located within the first 144 amino-terminal amino acids. Pdx-1 is also able to bind and activate transcription from the A3 element of the human insulin gene promoter in yeast. Analysis of the effects of two-point mutations (Q59L and R197H) in the PDX-1 gene found in type II diabetes patients showed that both point mutations interfere with the ability of Pdx-1 to bind to DNA and to activate transcription in yeast.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. [Surgery for pancreatic neuroendocrine tumors].

    PubMed

    Shibata, Chikashi; Egawa, Shin-Ichi; Motoi, Fuyuhiko; Morikawa, Takanori; Naitoh, Takeshi; Unno, Michiaki; Sasaki, Iwao

    2012-11-01

    Approximately half of pancreatic neuroendocrine tumors (PNETs) are nonfunctioning, and insulinoma and gastrinoma are frequent forms of functioning tumors. The treatment of patients with PNETs should be based on the consideration that more than half are malignant except for insulinomas. Multiple endocrine neoplasia type 1 (MEN1) is often complicated with gastrinoma. Endoscopic ultrasound and somatostain receptor scintigraphy are useful in diagnosing PNETs, and the selective arterial secretagogue injection test is performed if necessary. WHO2010 is available as a histopathologic grading system of malignancy. Although surgical resection should first be considered as a treatment for PNETs, liver metastasis is a major factor hindering resection. In Japan, the choices of drugs to treat liver metastases are too few. In patients with MEN1 in whom PNETS are frequently multiple, we should perform procedures that preserve pancreatic function, although some patients may require total pancreatectomy for the complete resection of tumors. The indications for total pancreatectomy should be determined individually based on the tumor status and patient age. PMID:23330458

  12. 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

  13. Clinical significance of serum pancreatic enzymes in the quiescent phase of chronic pancreatitis.

    PubMed

    Lesi, C; Melzi D'Eril, G V; Pavesi, F; Scandellari, A; Faccenda, F; Grazia Casertano, M; Savoia, M; Zoni, L; Peppi, M

    1985-08-01

    The most commonly used serum enzymes in pancreatic diseases are total amylase, pancreatic isoamylase, lipase and trypsin. To determine which of these enzymes is the most useful in the diagnosis of clinically quiescent chronic pancreatitis and which enzyme best reflects exocrine functional reserve, we studied 22 healthy control subjects, 44 patients with gastrointestinal, liver and biliary tract diseases, and 25 patients with chronic pancreatitis. On the basis of duodenal intubation, the latter were divided into two subgroups: one group of 13 patients with slight to moderate secretion deficiency and another of 12 patients with severe exocrine insufficiency. Of the enzymes studied, lipase, trypsin and pancreatic isoamylase are equally suitable for the evaluation of function in severe chronic pancreatitis, but not for the early diagnosis of the disease. Results for total amylase are not reliable so that its use in the study of chronic pancreatitis is not advisable.

  14. [Pancreatic pseudocysts].

    PubMed

    Stăncescu, M; Ciurea, S

    1989-01-01

    Clinical, evolutive and therapeutical aspects were studied, of 66 cases of patients with pancreatic pseudocysts hospitalized in the clinic over a period of 27 years. Particular modalities of onset were, those of patients with duodenal stenosis, mechanical jaundice, ascites and pleurisy, those in whom symptomatology suggested kidney or cholecystic disease. The intraoperative diagnosis raises the problem of differentiating a retroperitoneal tumor, identifying the possible association with a pancreatic cancer, and the condition when the pseudocysts are found at a certain distance from the pancreas itself. The therapeutical methods are codified, but recidives are possible. Cholecystectomy removes the biliary cause of pancreatitis which can determine the development of pseudocysts. The death rate of these cases was 6.3%.

  15. SERCA2 Deficiency Impairs Pancreatic β-Cell Function in Response to Diet-Induced Obesity.

    PubMed

    Tong, Xin; Kono, Tatsuyoshi; Anderson-Baucum, Emily K; Yamamoto, Wataru; Gilon, Patrick; Lebeche, Djamel; Day, Richard N; Shull, Gary E; Evans-Molina, Carmella

    2016-10-01

    The sarcoendoplasmic reticulum (ER) Ca(2+) ATPase 2 (SERCA2) pump is a P-type ATPase tasked with the maintenance of ER Ca(2+) stores. Whereas β-cell SERCA2 expression is reduced in diabetes, the role of SERCA2 in the regulation of whole-body glucose homeostasis has remained uncharacterized. To this end, SERCA2 heterozygous mice (S2HET) were challenged with a high-fat diet (HFD) containing 45% of kilocalories from fat. After 16 weeks of the HFD, S2HET mice were hyperglycemic and glucose intolerant, but adiposity and insulin sensitivity were not different between HFD-fed S2HET mice and HFD-fed wild-type controls. Consistent with a defect in β-cell function, insulin secretion, glucose-induced cytosolic Ca(2+) mobilization, and the onset of steady-state glucose-induced Ca(2+) oscillations were impaired in HFD-fed S2HET islets. Moreover, HFD-fed S2HET mice exhibited reduced β-cell mass and proliferation, altered insulin production and proinsulin processing, and increased islet ER stress and death. In contrast, SERCA2 activation with a small molecule allosteric activator increased ER Ca(2+) storage and rescued tunicamycin-induced β-cell death. In aggregate, these data suggest a critical role for SERCA2 and the regulation of ER Ca(2+) homeostasis in the β-cell compensatory response to diet-induced obesity.

  16. SERCA2 Deficiency Impairs Pancreatic β-Cell Function in Response to Diet-Induced Obesity.

    PubMed

    Tong, Xin; Kono, Tatsuyoshi; Anderson-Baucum, Emily K; Yamamoto, Wataru; Gilon, Patrick; Lebeche, Djamel; Day, Richard N; Shull, Gary E; Evans-Molina, Carmella

    2016-10-01

    The sarcoendoplasmic reticulum (ER) Ca(2+) ATPase 2 (SERCA2) pump is a P-type ATPase tasked with the maintenance of ER Ca(2+) stores. Whereas β-cell SERCA2 expression is reduced in diabetes, the role of SERCA2 in the regulation of whole-body glucose homeostasis has remained uncharacterized. To this end, SERCA2 heterozygous mice (S2HET) were challenged with a high-fat diet (HFD) containing 45% of kilocalories from fat. After 16 weeks of the HFD, S2HET mice were hyperglycemic and glucose intolerant, but adiposity and insulin sensitivity were not different between HFD-fed S2HET mice and HFD-fed wild-type controls. Consistent with a defect in β-cell function, insulin secretion, glucose-induced cytosolic Ca(2+) mobilization, and the onset of steady-state glucose-induced Ca(2+) oscillations were impaired in HFD-fed S2HET islets. Moreover, HFD-fed S2HET mice exhibited reduced β-cell mass and proliferation, altered insulin production and proinsulin processing, and increased islet ER stress and death. In contrast, SERCA2 activation with a small molecule allosteric activator increased ER Ca(2+) storage and rescued tunicamycin-induced β-cell death. In aggregate, these data suggest a critical role for SERCA2 and the regulation of ER Ca(2+) homeostasis in the β-cell compensatory response to diet-induced obesity. PMID:27489309

  17. 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.

  18. 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

  19. 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

  20. Functional role of glutamine 28 and arginine 39 in double stranded RNA cleavage by human pancreatic ribonuclease.

    PubMed

    Rehman, Md Tabish; Dey, Punyatirtha; Hassan, Md Imtaiyaz; Ahmad, Faizan; Batra, Janendra K

    2011-03-08

    Human pancreatic ribonuclease (HPR), a member of RNase A superfamily, has a high activity on double stranded (ds) RNA. By virtue of this activity HPR appears to be involved in the host-defense against pathogenic viruses. To delineate the mechanism of dsRNA cleavage by HPR, we have investigated the role of glutamine 28 and arginine 39 of HPR in its activity on dsRNA. A non-basic residue glycine 38, earlier shown to be important for dsRNA cleavage by HPR was also included in the study in the context of glutamine 28 and arginine 39. Nine variants of HPR respectively containing Q28A, Q28L, R39A, G38D, Q28A/R39A, Q28L/R39A, Q28A/G38D, R39A/G38D and Q28A/G38D/R39A mutations were generated and functionally characterized. The far-UV CD-spectral analysis revealed all variants, except R39A, to have structures similar to that of HPR. The catalytic activity of all HPR variants on single stranded RNA substrate was similar to that of HPR, whereas on dsRNA, the catalytic efficiency of all single residue variants, except for the Q28L, was significantly reduced. The dsRNA cleavage activity of R39A/G38D and Q28A/G38D/R39A variants was most drastically reduced to 4% of that of HPR. The variants having reduced dsRNA cleavage activity also had reduction in their dsDNA melting activity and thermal stability. Our results indicate that in HPR both glutamine 28 and arginine 39 are important for the cleavage of dsRNA. Although these residues are not directly involved in catalysis, both arginine 39 and glutamine 28 appear to be facilitating a productive substrate-enzyme interaction during the dsRNA cleavage by HPR.

  1. Isolated lymphoplasmacytic sclerosing pancreatitis involving the pancreatic tail.

    PubMed

    Kim, Tad; Grobmyer, Stephen R; Dixon, Lisa R; Hochwald, Steven N

    2008-07-01

    We present an interesting case of a 62-year-old woman with a 3-month history of vague, left-sided abdominal pain. CT imaging revealed a hypodense lesion in the tail of the pancreas. The patient had no history of pancreatitis or autoimmune diseases. Laboratory testing revealed a normal CA19-9 (33 U/mL) and an elevated IgG4 (133 mg/dL). Due to concerns of pancreatic malignancy, she underwent operation. We found a dense, inflammatory mass in the tail of the pancreas, which was removed via an open distal pancreatectomy with splenectomy. Histologic analysis revealed a pancreas with sclerotic ducts and surrounding lymphoplasmacytic inflammation most consistent with lymphoplasmacytic sclerosing pancreatitis (LPSP). LPSP, also termed autoimmune pancreatitis, is a benign disease of the pancreas, which can mimic pancreatic adenocarcinoma. It is the most common benign finding diagnosed on pathology after pancreatic resection for presumed malignancy. LPSP most commonly involves the head and, more uncommonly, the tail of the pancreas. It can be successfully treated with steroids obviating the need for resection. IgG4 levels may assist in recognition of this disease. As our experience with utilization of IgG4 testing and knowledge of the systemic nature of LPSP increase, patients with this disease may be spared unnecessary resection.

  2. Human pancreatic cell autotransplantation following total pancreatectomy.

    PubMed Central

    Traverso, L W; Abou-Zamzam, A M; Longmire, W P

    1981-01-01

    During total pancreaticoduodenectomy for chronic pancreatitis, four patients received an intraportal pancreatic mixed-cell autograft prepared by collagenase digestion. The technique of this autotransplantation procedure was successfully developed using a normal canine pancreas, but has proved difficult to apply in the human chronic pancreatitis model. Our four patients became insulin-dependent, with proof of intrahepatic insulin production in only one patient. Three factors have contributed to the lack of graft success: 1) the preoperative endocrine status, 2) systemic hypotension and portal hypertension secondary to graft infusion, and 3) difficulty applying the successful technique in a normal dog pancreas to an extensively scarred human pancreas. The preoperative insulin response during a glucose tolerance test was blunted or delayed in the three patients tested. An immediate decrease in blood pressure and rise in portal pressure occurred in every patient and prevented infusion of the entire graft (30-50%) in three patients. Unfortunately, the patient with the most compromised insulin status was the only patient able to receive the entire graft. Our experience would indicate that further refinements in technique are necessary to prevent the vascular reaction and allow infusion of the entire graft. Furthermore, normal islet cell function is necessary before a successful graft can be expected. PMID:6781424

  3. 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 ...

  4. 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

  5. Inflammatory mediators in acute pancreatitis.

    PubMed

    Bhatia, M; Brady, M; Shokuhi, S; Christmas, S; Neoptolemos, J P; Slavin, J

    2000-02-01

    Inflammatory mediators play a key role in acute pancreatitis and the resultant multiple organ dysfunction syndrome, which is the primary cause of death in this condition. Recent studies have confirmed the critical role played by inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, IL-8, PAF, IL-10, C5a, ICAM-1, and substance P. The systemic effects of acute pancreatitis have many similarities to those of other conditions such as septicaemia, severe burns, and trauma. The delay between the onset of inflammation in the pancreas and the development of the systemic response makes acute pancreatitis an ideal experimental and clinical model with which to study the role of inflammatory mediators and to test novel therapies. Elucidation of the key mediators involved in the pathogenesis of acute pancreatitis will facilitate the development of clinically effective anti-inflammatory therapy.

  6. Werner syndrome as a hereditary risk factor for exocrine pancreatic cancer: potential role of WRN in pancreatic tumorigenesis and patient-tailored therapy.

    PubMed

    Chun, Stephen G; Yee, Nelson S

    2010-09-01

    Advanced age is considered a risk factor for pancreatic cancer, but this relationship at the molecular and genetic level remains unclear. We present a clinical case series focusing on an association between pancreatic adenocarcinoma and Werner syndrome (WS) that is an autosomal recessive genetic disorder characterized by accelerated aging and cancer predisposition, and is caused by loss-of-function mutations in the WS RecQ helicase gene (WRN). Although pancreatic adenocarcinoma mostly occurs in a sporadic fashion, a minority of cases occurs in the context of susceptible individuals with hereditary syndromes. While WS has not been previously recognized as a risk factor for developing malignant tumors of the exocrine pancreas, the clinicopathologic features of three reported patients suggest a contributory role of WRN deficiency in pancreatic carcinogenesis. Molecular genetic analyses support the role of WRN as a tumor suppressor gene, although recent evidence reveals that WRN can alternatively promote oncogenicity depending on the molecular context. Based upon the clinico-pathologic features of these patients and the role of WRN in experimental models, we propose that its loss-of-function predisposes the development of pancreatic adenocarcinoma through epigenetic silencing or loss-of-heterozygosity of WRN. To test this hypothesis, we are investigating the mechanistic role of WRN in pancreatic cancer models including a pancreatic adenocarcinoma cell line generated from a human with WS. These studies are expected to provide new insight into the relationship between aging and pancreatic tumorigenesis, and facilitate development of novel strategies for patient-tailored interventions in this deadly malignancy.

  7. PDX-1 and MafA play a crucial role in pancreatic beta-cell differentiation and maintenance of mature beta-cell function.

    PubMed

    Kaneto, Hideaki; Miyatsuka, Takeshi; Kawamori, Dan; Yamamoto, Kaoru; Kato, Ken; Shiraiwa, Toshihiko; Katakami, Naoto; Yamasaki, Yoshimitsu; Matsuhisa, Munehide; Matsuoka, Taka-Aki

    2008-05-01

    Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in pancreas development, beta-cell differentiation, and maintenance of mature beta-cell function. PDX-1 expression is maintained in pancreatic precursor cells during pancreas development but becomes restricted to beta-cells in mature pancreas. In mature beta-cells, PDX-1 transactivates the insulin and other genes involved in glucose sensing and metabolism such as GLUT2 and glucokinase. MafA is a recently isolated beta-cell-specific transcription factor which functions as a potent activator of insulin gene transcription. Furthermore, these transcription factors play an important role in induction of insulin-producing cells in various non-beta-cells and thus could be therapeutic targets for diabetes. On the other hand, under diabetic conditions, expression and/or activities of PDX-1 and MafA in beta-cells are reduced, which leads to suppression of insulin biosynthesis and secretion. It is likely that alteration of such transcription factors explains, at least in part, the molecular mechanism for beta-cell glucose toxicity found in diabetes.

  8. Autocrine/paracrine function of nicotinic acid adenine dinucleotide phosphate (NAADP) for glucose homeostasis in pancreatic β-cells and adipocytes.

    PubMed

    Park, Kwang-Hyun; Kim, Byung-Ju; Shawl, Asif Iqbal; Han, Myung-Kwan; Lee, Hon Cheung; Kim, Uh-Hyun

    2013-12-01

    Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger for mobilizing Ca(2+) from intracellular stores in various cell types. Extracellular application of NAADP has been shown to elicit intracellular Ca(2+) signals, indicating that it is readily transported into cells. However, little is known about the functional role of this NAADP uptake system. Here, we show that NAADP is effectively transported into selected cell types involved in glucose homeostasis, such as adipocytes and pancreatic β-cells, but not the acinar cells, in a high glucose-dependent manner. NAADP uptake was inhibitable by Ned-19, a NAADP mimic; dipyridamole, a nucleoside inhibitor; or NaN3, a metabolic inhibitor or under Ca(2+)-free conditions. Furthermore, NAADP was found to be released from pancreatic islets upon stimulation by high glucose. Consistently, administration of NAADP to type 2 diabetic mice improved glucose tolerance. We propose that NAADP is functioning as an autocrine/paracrine hormone important in glucose homeostasis. NAADP is thus a potential antidiabetic agent with therapeutic relevance.

  9. Lipase turbidimetric assay and acute pancreatitis.

    PubMed

    Orda, R; Orda, S; Baron, J; Wiznitzer, T

    1984-04-01

    The simplified turbidimetric assay for lipase activity was used for the differential diagnosis of acute pancreatitis. Serum lipase levels were found to be increased in a group of 17 patients in whom acute pancreatitis was clinically suspected and confirmed by a high ACCR and decreased uptake of the radionuclide in the pancreas scan. The lipase levels were within normal limits in a control group of 14 patients suffering from diseases other than acute pancreatitis. The turbidimetric test was helpful for rapid quantitative determination of serum lipase and thus for the early and accurate diagnosis of acute pancreatitis. PMID:6200277

  10. 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)…

  11. First State Fitness Test. A Measurement of Functional Health.

    ERIC Educational Resources Information Center

    Brown, Timothy; And Others

    This test is designed to measure the functional health of young people. Functional health refers to those factors relating to personal health that can be improved with regular exercise. This test is unique in comparison to other physical fitness tests because of the absence of motor skill items which have no relationship to an individual's…

  12. Conservation of pancreatic tissue by combined gastric, biliary, and pancreatic duct drainage for pain from chronic pancreatitis.

    PubMed

    Warshaw, A L

    1985-04-01

    In patients with chronic pancreatitis, the sclerosing process of the pancreas may constrict not only the pancreatic duct for also the bile duct and duodenum. This study analyzes the prevalence of these obstructive lesions in 58 consecutive patients with chronic pancreatitis requiring surgery for either pain (57 patients) or for painless jaundice (1 patient). There was significant biliary obstruction in 21, 4 of whom also had symptomatic duodenal obstruction. All 21 patients with biliary and duodenal obstruction were among the 38 with a dilated pancreatic duct suitable for pancreaticojejunostomy (modified Puestow procedure). None of the 20 patients with small duct pancreatitis had biliary or duodenal obstruction. Pseudocysts were distributed evenly between the two groups (9 of 38 patients with a dilated duct versus 4 of 20 patients with small duct pancreatitis). Pancreaticojejunostomy combined with choledochoenterostomy and gastrojejunostomy in appropriately selected patients provided good to excellent long-term (mean 3.6 years) relief of pain in 30 of 36 patients (83 percent). There was no correlation between successful relief of pain and development of pancreatic exocrine or endocrine insufficiency or calcification. Stenosis of the bile duct developed some years subsequent to pancreaticojejunostomy in four patients and required a second operation for choledochoenterostomy in three. Three other patients required secondary pancreatic resections due to failure of the pancreaticojejunostomy to relieve pain. It is often possible to effect excellent relief of symptoms with maximal conservation of remaining pancreatic functions despite sclerotic obstruction of multiple organ systems.

  13. An overview of the diagnosis and management of nutrition in chronic pancreatitis.

    PubMed

    Afghani, Elham; Sinha, Amitasha; Singh, Vikesh K

    2014-06-01

    Chronic pancreatitis is characterized by long-standing inflammation of the pancreas, which results in fibrosis and the gradual loss of pancreatic function. The loss of islets and acinar cells results in diabetes and exocrine insufficiency, respectively. Exocrine insufficiency can result in maldigestion of fat, protein, and carbohydrate as well as vitamins and minerals. Patients may present with variable severity of disease, from mild to severe. The diagnosis of chronic pancreatitis can be challenging, especially in patients with early or mild disease who have few to no morphologic abnormalities on standard abdominal imaging studies. A number of imaging modalities and tests have evolved to aid in the diagnosis of chronic pancreatitis based on changes in structure or function. Clinicians typically focus on treating pain in chronic pancreatitis as opposed to exocrine insufficiency, despite the fact that maldigestion and malabsorption can result in nutrition deficiencies. The aims of this review are to describe the various modalities used to diagnose chronic pancreatitis, to illustrate the nutrition deficiencies associated with exocrine insufficiency, and to provide an overview of nutrition assessment and treatment in these patients.

  14. 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

  15. [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

  16. [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.

  17. 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

  18. The Epidemiology of Pancreatitis and Pancreatic Cancer

    PubMed Central

    Yadav, Dhiraj; Lowenfels, Albert B.

    2013-01-01

    Acute pancreatitis is one of the most frequent gastrointestinal causes for hospital admission in the US. Chronic pancreatitis, although lower in incidence, significantly reduces patients’ quality of life. Pancreatic cancer has high mortality and is 1 of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect Blacks more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. PMID:23622135

  19. 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…

  20. 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.

  1. Does pancreatic ductal anatomy play a role in determining outcomes of pancreatic anastomoses?

    PubMed

    Shukla, P J; Sakpal, S V; Maharaj, R

    2011-02-01

    Pancreatoduodenectomy (PD) is the surgical procedure performed for cancers of the head of the pancreas. Despite a substantial reduction in mortality rates following PD, morbidity remains high secondary to major post-operative complications. Post-operative pancreatic fistula (POPF), the commonest major complication following PD, results from the failure of the pancreato-enteric anastomosis. There appears to be a correlation between intrinsic pancreatic features like the texture of the gland and duct size and the outcome of the pancreatic anastomosis. Based on current clinical research data, we propose a new hypothesis called the "pancreatic ductal anatomy" concept. We hypothesize that morphological variations, anomalies or aberrations of the main pancreatic duct play a role in the outcome of the pancreatic anastomosis, irrespective of its type. The consequence of aberrant ductal anatomy is that certain areas of the remnant pancreas remain either undrained or partially drained, or have blocked ductules/ducts. This results in localized obstructive pancreatitis causing an inflammatory reaction which jeopardizes the anastomosis. We also propose two maneuvers which could possibly play a role in predicting potential problems and also planning the surgical resection and reconstruction in order to reduce the incidence of POPF. The first modality is the use of pre-operative magnetic resonance imaging (MRI) of the pancreatic duct, and the second maneuver is the gentle cannulation test of the pancreatic duct with a soft, narrow tube following transection of the pancreatic neck. These factors would alert the surgeon about potential ductal variations and could facilitate the surgical approach.

  2. 33 CFR 157.12f - Workshop functional test requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12f Workshop functional test requirements... the specific design of equipment. A completed workshop certificate including the delivery test...; (2) A check of the correct function of the signal processor and the recording equipment...

  3. Traumatic pancreatic pseudocysts.

    PubMed

    Popoola, D; Lou, M A; Sims, E H

    1983-05-01

    At the Martin Luther King, Jr, General Hospital in Los Angeles, during the period from June 1972 to April 1981, seven patients underwent surgery for traumatic pancreatic pseudocysts. The overall average age was 28 and the average hospital stay was 31 days. Ultrasound was the most useful test for diagnosis and follow-up. Preoperatively, serum amylases were not consistently elevated. Overall recurrences and complications totaled 57 percent. There were no deaths. The authors consider a large cystogastrostomy the treatment of choice for mature cysts that are satisfactorily adherent to the stomach. The second preference is a Roux-en-Y cystojejunostomy. External drainage was employed for acute cysts that required drainage. A distal pancreatectomy was performed for patients with small pancreatic tail pseudocysts. Patients who underwent acute drainage were usually drained externally and had a poorer outcome than patients who were operated on later with internal drainage. When compared with another group of 15 alcoholic patients who were operated on for pancreatic pseudocysts, patients with traumatic pseudocysts had a poorer outcome.

  4. 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

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

    PubMed Central

    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

  6. Extensive Molecular Analysis Suggested the Strong Genetic Heterogeneity of Idiopathic Chronic Pancreatitis

    PubMed Central

    Sofia, Valentina Maria; Da Sacco, Letizia; Surace, Cecilia; Tomaiuolo, Anna Cristina; Genovese, Silvia; Grotta, Simona; Gnazzo, Maria; Petrocchi, Stefano; Ciocca, Laura; Alghisi, Federico; Montemitro, Enza; Martemucci, Luigi; Elce, Ausilia; Lucidi, Vincenzina; Castaldo, Giuseppe; Angioni, Adriano

    2016-01-01

    Genetic features of chronic pancreatitis (CP) have been investigated extensively, mainly by testing genes associated to the trypsinogen activation pathway. However, different molecular pathways involving other genes may be implicated in CP pathogenesis. A total of 80 patients with idiopathic chronic pancreatitis (ICP) were investigated using a Next-Generation Sequencing (NGS) approach with a panel of 70 genes related to six different pancreatic pathways: premature activation of trypsinogen, modifier genes of cystic fibrosis phenotype, pancreatic secretion and ion homeostasis, calcium signaling and zymogen granules (ZG) exocytosis, autophagy and autoimmune pancreatitis-related genes. We detected mutations in 34 out of 70 genes examined; of the 80 patients, 64 (80.0%) were positive for mutations in one or more genes and 16 (20.0%) had no mutations. Mutations in CFTR were detected in 32 of the 80 patients (40.0%) and 22 of them exhibited at least one mutation in genes of other pancreatic pathways. Of the remaining 48 patients, 13/80 (16.3%) had mutations in genes involved in premature activation of trypsinogen and 19/80 (23.8%) had mutations only in genes of the other pathways: 38 (59.3%) of the 64 patients positive for mutations showed variants in two or more genes. Our data, although to be extended with functional analysis of novel mutations, suggest a high rate of genetic heterogeneity in CP and that trans-heterozygosity may predispose to the ICP phenotype. PMID:27264265

  7. 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…

  8. 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…

  9. Therapeutic Targeting of the Warburg Effect in Pancreatic Cancer Relies on an Absence of p53 Function.

    PubMed

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

    2015-08-15

    The "Warburg effect" describes a peculiar metabolic feature of many solid tumors, namely their increased glucose uptake and high glycolytic rates, which allow cancer cells to accumulate building blocks for the biosynthesis of macromolecules. 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 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 noninvasive 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 a biomarker to predict sensitivity to LDH-A inhibition, with regard to both real-time noninvasive imaging by 13C MRS as well as therapeutic response. PMID:26113084

  10. 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

  11. 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…

  12. 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

  13. Etiology and oncogenesis of pancreatic carcinoma.

    PubMed

    Dobrila-Dintinjana, Renata; Vanis, Nenad; Dintinjana, Marijan; Radić, Mladen

    2012-09-01

    Pancreatic cancer is the fourth leading cause of cancer death overall. The factors that favor the development of pancreatic cancer can be divided into hereditary and acquired. Cancerogenesis is best explained by a "multi-hit" hypothesis, charcterized with the developmental sequence of cellular mutatitions, forcing mutant cell to inappropriate proliferation and preventing its repair and programmed cell death (apoptosis). The most common mutations involve K-ras gene, epidermal growth factor (EGF-R) and HER2 gene. Continuous stimulation and secretion of vascular endothelial growth factor (VEGF) enhances the permeability of blood vessels provides nutrient supply to tumor site through newly formed vascular channels. This phenomena is known as vasculogenic mimicry. Loss of function of tumor-suppressor genes has been documented in pancreatic cancer, especially in CDKN2a, p53, DPC4 and BRCA2 genes. SDKN2A gene inactivation occurs in 95% of pancreatic adenocarcinoma. As regards acquired factors, smoking is only confirmed risk factor that increases the risk of pancreatic cancer. Diabetes, alcohol consumption, central obesity in men, infection with Helicobacter pylori and chronic pancreatitis are suspected, but not proven risk factors. Consumption of fruits and vegetables does not protect, while the consumption of meat processed at high temperatures increases the risk of pancreatic cancer. According to some studies, lykopene and folate levels are reduced in pancreatic carcinoma patients, reduced folate intake increases the risk of pancreatic carcinoma (48%), and this risk can be diminished by introducing folate-rich foods to diet, not by using pharmaceutical products. Occupational exposure to chlorinated hydrocarbons, vinyl chloride, nickel, chromium, insecticides and acrylic amide minimally increases the risk for pancreatic cancer. Exposure to cadmium (metal industry) associated with smoking result in the accumulation of cadmium in pancreatic tissue and the possible impact

  14. Etiology and oncogenesis of pancreatic carcinoma.

    PubMed

    Dobrila-Dintinjana, Renata; Vanis, Nenad; Dintinjana, Marijan; Radić, Mladen

    2012-09-01

    Pancreatic cancer is the fourth leading cause of cancer death overall. The factors that favor the development of pancreatic cancer can be divided into hereditary and acquired. Cancerogenesis is best explained by a "multi-hit" hypothesis, charcterized with the developmental sequence of cellular mutatitions, forcing mutant cell to inappropriate proliferation and preventing its repair and programmed cell death (apoptosis). The most common mutations involve K-ras gene, epidermal growth factor (EGF-R) and HER2 gene. Continuous stimulation and secretion of vascular endothelial growth factor (VEGF) enhances the permeability of blood vessels provides nutrient supply to tumor site through newly formed vascular channels. This phenomena is known as vasculogenic mimicry. Loss of function of tumor-suppressor genes has been documented in pancreatic cancer, especially in CDKN2a, p53, DPC4 and BRCA2 genes. SDKN2A gene inactivation occurs in 95% of pancreatic adenocarcinoma. As regards acquired factors, smoking is only confirmed risk factor that increases the risk of pancreatic cancer. Diabetes, alcohol consumption, central obesity in men, infection with Helicobacter pylori and chronic pancreatitis are suspected, but not proven risk factors. Consumption of fruits and vegetables does not protect, while the consumption of meat processed at high temperatures increases the risk of pancreatic cancer. According to some studies, lykopene and folate levels are reduced in pancreatic carcinoma patients, reduced folate intake increases the risk of pancreatic carcinoma (48%), and this risk can be diminished by introducing folate-rich foods to diet, not by using pharmaceutical products. Occupational exposure to chlorinated hydrocarbons, vinyl chloride, nickel, chromium, insecticides and acrylic amide minimally increases the risk for pancreatic cancer. Exposure to cadmium (metal industry) associated with smoking result in the accumulation of cadmium in pancreatic tissue and the possible impact

  15. 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

  16. 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

  17. Routine liver function tests and serum amylase determinations after biliary lithotripsy: are they necessary?

    PubMed

    Goodacre, B W; Malone, D E; Fache, J S; Rawat, B; Burhenne, H J

    1990-10-01

    Shock-wave-induced soft-tissue damage after biliary extracorporeal shock-wave lithotripsy (BESWL) has been reported. Every patient treated in Vancouver has, therefore, had liver function tests and serum amylase levels measured before and within 6 days after BESWL. All patients had symptomatic cholecystolithiasis with normal pre-BESWL biochemistry. Analysis of 311 patients after treatment with the Siemens Lithostar unit showed elevation of one or more laboratory value in 19% (60/311). Serum aspartate transaminase level was most frequently abnormal (38 cases). The majority of abnormalities were mild, less than two times normal levels. Clinically significant complications occurred in five patients (three pancreatitis, one cholecystitis, one common bile duct obstruction); four of these occurred 1 week or more after treatment. The results of routine laboratory tests could not be used to predict complications. No correlation was seen between abnormal values and number of shock waves administered or peak shock-wave pressure. Of 112 patients surveyed at the time of post-BESWL enzyme measurement, 49 (44%) reported a degree of pain, which was severe in eight cases. Presence of severe pain correlated strongly (p less than .001) with abnormal laboratory findings, however not with the degree of abnormality. As results of these laboratory tests are nonspecific, have not been shown to correlate with the degree of severity of BESWL-induced tissue damage, and do not predict complications, the tests are of little value in the absence of clinical signs and symptoms. These conclusions, however, apply only to the Siemens Lithostar Plus with patients treated in the steep left posterior oblique position. Cost savings can be expected if routine post-BESWL biochemical tests are abandoned.

  18. Hyperlipidaemia and outcome in acute pancreatitis.

    PubMed

    Balachandra, S; Virlos, I T; King, N K K; Siriwardana, H P P; France, M W; Siriwardena, A K

    2006-02-01

    There is a well-recognised association between hyperlipidaemia and acute pancreatitis. However, the role of hyperlipidaemia in modulating disease course is not clear. The aim of the study was to conduct a prospective study in acute pancreatitis to assess the relation between hyperlipidaemia and disease severity using current disease descriptors. The study population constituted 43 patients with acute pancreatitis, admitted during the calendar year 2001. There were 19 (44%) males. The median (range) age was 50 (21-86) years. Serum triglycerides, cholesterol and high-density lipids were measured on admission. Patients were followed-up for at least 6 months after discharge. Principal outcomes were relation between hyperlipidaemia and peri-pancreatic complications and end-of-episode disease severity. The results showed that hypertriglyceridaemia was present in 14 patients (33%). There was a significant difference in mean (SEM) serum triglyceride levels between patients with alcohol-induced pancreatitis compared with pancreatitis of other aetiologies [3.07 (1.0) mmol/l vs. 1.26 (0.11) mmol/l; p = 0.03, Fisher's exact test]. There was no correlation between admission hypertriglyceridaemia and admission APACHE II score (r(2) = 0.0015). Similarly, there was no correlation between triglyceride level and either pancreatic inflammatory complications or final outcome. In conclusion, this study has demonstrated that there was no significant correlation between hypertriglyceridaemia and either complications of disease or overall end-of-episode severity in this population of patients with acute pancreatitis.

  19. Pancreatic cancer screening: state of the art.

    PubMed

    Gemmel, Christian; Eickhoff, Axel; Helmstädter, Lars; Riemann, Jürgen F

    2009-02-01

    Pancreatic cancer is a devastating disease with a median survival of approximately 6 months after diagnosis. Many factors are associated with a worse outcome; examples include late diagnosis, low resection rate, aggressive tumor behavior and a lack of an effective chemotherapy regimen. Owing to the low prevalence of pancreatic cancer relative to the diagnostic accuracy of present detection methods and the absence of promising treatment modalities, even in early stages, it is currently neither advisable nor cost effective to screen the general population. Efforts are focused on early screening of selected high-risk-cohorts, who account for approximately 10% of patients with pancreatic cancer. These include patients with chronic pancreatitis, individuals with a family history of pancreatic cancer, patients with hereditary pancreatitis, Peutz-Jeghers syndrome, cystic fibrosis or familial atypical multiple mole melanoma. At present, a multimodal-screening approach of endoscopic ultrasound, computed tomography and endoscopic retrograde cholangiopancreatography appears to be the most effective method to screen for pancreatic cancer in high-risk patients. Continued efforts are needed to elucidate effective testing to identify patients with nonhereditary risk factors who will benefit from screening protocols. A combined approach of serum markers, genetic markers and specific imaging studies may prove to be the future of pancreatic screening. PMID:19210116

  20. 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.

  1. Formal Functional Test Designs: Bridging the Gap Between Test Requirements and Test Specifications

    NASA Technical Reports Server (NTRS)

    Hops, Jonathan

    1993-01-01

    This presentation describes the testing life cycle, the purpose of the test design phase, and test design methods and gives an example application. Also included is a description of Test Representation Language (TRL), a summary of the language, and an example of an application of TRL. A sample test requirement and sample test design are included.

  2. 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

  3. Pancreatic-pleural fistula in chronic pancreatitis.

    PubMed

    Elkaoui, Hakim; Atoini, Fouad; Bouchentouf, Sidi Mohamed; El Omari, Fatima; Mahi, Mohamed; Ait Ali, Abdelmounaim; Bounaim, Ahmed; Sair, Khalid; Zentar, Aziz

    2012-03-01

    Pancreatic-pleural fistula is a rare condition and few data related to its diagnosis and treatment are available. A fistulous connection linking the pancreas with the pleura via the diaphragm or mediastinum through the retroperitoneal area is formed. We report on a case with pancreatic-pleural fistula at its early stages in an alcoholic male patient aged 45 years with known chronic pancreatitis. The operation by Roux-en-Y jejuno-pseudocystostomy was followed by chest tube drainage. PMID:22560825

  4. 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.

  5. 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.

  6. 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.

  7. SOX2 functions as a molecular rheostat to control the growth, tumorigenicity and drug responses of pancreatic ductal adenocarcinoma cells

    PubMed Central

    Wuebben, Erin L.; Wilder, Phillip J.; Cox, Jesse L.; Grunkemeyer, James A.; Caffrey, Thomas; Hollingsworth, Michael A.; Rizzino, Angie

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly deadly malignancy. Expression of the stem cell transcription factor SOX2 increases during progression of PDAC. Knockdown of SOX2 in PDAC cell lines decreases growth in vitro; whereas, stable overexpression of SOX2 in one PDAC cell line reportedly increases growth in vitro. Here, we reexamined the role of SOX2 in PDAC cells, because inducible SOX2 overexpression in other tumor cell types inhibits growth. In this study, four PDAC cell lines were engineered for inducible overexpression of SOX2 or inducible knockdown of SOX2. Remarkably, inducible overexpression of SOX2 in PDAC cells inhibits growth in vitro and reduces tumorigenicity. Additionally, inducible knockdown of SOX2 in PDAC cells reduces growth in vitro and in vivo. Thus, growth and tumorigenicity of PDAC cells is highly dependent on the expression of optimal levels of SOX2 – a hallmark of molecular rheostats. We also determined that SOX2 alters the responses of PDAC cells to drugs used in PDAC clinical trials. Increasing SOX2 reduces growth inhibition mediated by MEK and AKT inhibitors; whereas knockdown of SOX2 further reduces growth when PDAC cells are treated with these inhibitors. Thus, targeting SOX2, or its mode of action, could improve the treatment of PDAC. PMID:27145457

  8. Overexpression of ankyrin1 promotes pancreatic cancer cell growth

    PubMed Central

    Omura, Noriyuki; Mizuma, Masamichi; MacGregor, Anne; Hong, Seung-Mo; Ayars, Michael; Almario, Jose Alejandro; Borges, Michael; Kanda, Mitsuro; Li, Ang; Vincent, Audrey; Maitra, Anirban; Goggins, Michael

    2016-01-01

    The methylation status of a promoter influences gene expression and aberrant methylation during tumor development has important functional consequences for pancreatic and other cancers. Using methylated CpG island amplification and promoter microarrays, we identified ANK1 as hypomethylated in pancreatic cancers. Expression analysis determined ANK1 as commonly overexpressed in pancreatic cancers relative to normal pancreas. ANK1 was co-expressed with miR-486 in pancreatic cancer cells. Stable knockdown of ANK1 in the pancreatic cancer cell line AsPC1 led to changes in cell morphology, and decreases in colony formation. Stable knockdown of ANK1 also marked reduced the growth of tumors in athymic nude mice. Among patients undergoing pancreaticoduodenectomy, those with pancreatic cancers expressing ANK1 had a poorer prognosis than those without ANK1 expression. These findings indicate a role for ANK1 overexpression in mediating pancreatic cancer tumorigenicity. PMID:27144336

  9. Construct validity of functional capacity tests in healthy workers

    PubMed Central

    2013-01-01

    Background Functional Capacity (FC) is a multidimensional construct within the activity domain of the International Classification of Functioning, Disability and Health framework (ICF). Functional capacity evaluations (FCEs) are assessments of work-related FC. The extent to which these work-related FC tests are associated to bio-, psycho-, or social factors is unknown. The aims of this study were to test relationships between FC tests and other ICF factors in a sample of healthy workers, and to determine the amount of statistical variance in FC tests that can be explained by these factors. Methods A cross sectional study. The sample was comprised of 403 healthy workers who completed material handling FC tests (lifting low, overhead lifting, and carrying) and static work FC tests (overhead working and standing forward bend). The explainable variables were; six muscle strength tests; aerobic capacity test; and questionnaires regarding personal factors (age, gender, body height, body weight, and education), psychological factors (mental health, vitality, and general health perceptions), and social factors (perception of work, physical workloads, sport-, leisure time-, and work-index). A priori construct validity hypotheses were formulated and analyzed by means of correlation coefficients and regression analyses. Results Moderate correlations were detected between material handling FC tests and muscle strength, gender, body weight, and body height. As for static work FC tests; overhead working correlated fair with aerobic capacity and handgrip strength, and low with the sport-index and perception of work. For standing forward bend FC test, all hypotheses were rejected. The regression model revealed that 61% to 62% of material handling FC tests were explained by physical factors. Five to 15% of static work FC tests were explained by physical and social factors. Conclusions The current study revealed that, in a sample of healthy workers, material handling FC tests were

  10. Influence of bile flow interruption on acute experimental pancreatitis.

    PubMed

    Sarli, L; Gafà, M; Lupi, M; Peracchia, A

    1984-01-01

    The influence of bile flow interruption on the pathogenesis of acute pancreatitis has been evaluated in the rat. The pancreatitis was induced by Pfeffer's technique and the severity of the disease was assessed by a macroscopic examination of the pancreatic damage and the calculation of amylase-to-creatinine clearance ratio (ACCR) as well. The results showed that the bile reflux into the pancreas made the pancreatic lesions caused by stasis in the gland associated with hyperstimulation of exocrine secretion more severe. On the other hand the bile reflux had no influence when the pancreatitis was due to flowing back of duodenal contents into the pancreas (closed duodenal loop). It was concluded that the bile effect is probably consistent with a pressure mechanism. In addition the reliability of ACCR in the diagnosis of acute pancreatitis was confirmed, and the test was effective in detecting even milder pancreatic damages. PMID:6206023

  11. Endoscopic ultrasonography for evaluating patients with recurrent pancreatitis.

    PubMed

    Petrone, Maria Chiara; Arcidiacono, Paolo G; Testoni, Pier Alberto

    2008-02-21

    Acute recurrent pancreatitis (ARP) is still a complex diagnostic and therapeutic challenge in clinical practice. In up to 30% of cases of ARP, it is not possible to establish the etiology of the disease. In the other 70%, many factors play an etiological role in ARP: microlithiasis, sphincter of Oddi dysfunction (SOD), pancreas divisum, hereditary pancreatitis, cystic fibrosis, a choledochocele, annular pancreas, an anomalous pancreatobiliary junction, pancreatic tumors or chronic pancreatitis are diagnosed. EUS should be useful in ARP as it is sensitive for diagnosing bile duct stones, gallbladder sludge, pancreatic lesions, ductal abnormalities and chronic pancreatitis. Endoscopic ultrasound (EUS) appears to be diagnostic in the majority of patients with previously unexplained pancreatitis, and offers an alternative to endoscopic retrograde cholangiopancreatography (ERCP) as the initial diagnostic test in patients with ARP.

  12. 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...

  13. Transfer function tests of the Joy longwall shearer

    NASA Technical Reports Server (NTRS)

    Fisher, P. H., Jr.

    1978-01-01

    A series of operational tests was performed on the Joy longwall shearer located at the Bureau of Mines in Bructon, Pennsylvania. The purpose of these tests was to determine the transfer function and operational characteristics of the system. These characteristics will be used to generate a simulation model of the longwall shearer used in the development of the closed-loop vertical control system.

  14. Pancreatitis - series (image)

    MedlinePlus

    ... common bile duct and block the flow of pancreatic enzymes out of the pancreas into the intestine. Pancreatitis ... three to five days, to prevent secretion of enzymes by the pancreas. He will also receive pain medication to control ...

  15. Current progress in immunotherapy for pancreatic cancer.

    PubMed

    Foley, Kelly; Kim, Victoria; Jaffee, Elizabeth; Zheng, Lei

    2016-10-10

    Pancreatic cancer remains one of the most lethal cancers with few treatment options. Immune-based strategies to treat pancreatic cancer, such as immune checkpoint inhibitors, therapeutic vaccines, and combination immunotherapies, are showing promise where other approaches have failed. Immune checkpoint inhibitors, including anti-CTLA4, anti-PD-1, and anti-PD-L1 antibodies, are effective as single agents in immune sensitive cancers like melanoma, but lack efficacy in immune insensitive cancers including pancreatic cancer. However, these inhibitors are showing clinical activity, even in traditionally non-immunogenic cancers, when combined with other interventions, including chemotherapy, radiation therapy, and therapeutic vaccines. Therapeutic vaccines given together with immune modulating agents are of particular interest because vaccines are the most efficient way to induce effective anti-tumor T cell responses, which is required for immunotherapies to be effective. In pancreatic cancer, early studies suggest that vaccines can induce T cells that have the potential to recognize and kill pancreatic cancer cells, but the tumor microenvironment inhibits effective T cell trafficking and function. While progress has been made in the development of immunotherapies for pancreatic cancer over the last several years, additional trials are needed to better understand the signals within the tumor microenvironment that are formidable barriers to T cell infiltration and function. Additionally, as more pancreatic specific antigens are identified, immunotherapies will continue to be refined to provide the most significant clinical benefit.

  16. Preoperative Folfirinox for Resectable Pancreatic Adenocarcinoma - A Phase II Study

    ClinicalTrials.gov

    2016-02-16

    Pancreatic Adenocarcinoma; Poorly Differentiated Malignant Neoplasm; Resectable Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Undifferentiated Pancreatic Carcinoma

  17. 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

  18. State of the Art in Platelet Function Testing

    PubMed Central

    E. Kehrel, Beate; F. Brodde, Martin

    2013-01-01

    Summary Platelets perform many functions in hemostasis but also in other areas of physiology and pathology. Therefore, it is obvious that many different function tests have been developed, each one conceived and standardized for a special purpose. This review will summarize the different fields in which platelet function testing is currently in use; diagnostics of patients with bleeding disorders, monitoring patients’ response to anti-platelet therapy, monitoring in transfusion medicine (blood donors, platelet concentrates, and after transfusion), and monitoring in perioperative medicine to predict bleeding tendency. The second part of the review outlines different methods for platelet function testing, spanning bleeding time, and platelet counting as well as determining platelet adhesion, platelet secretion, platelet aggregation, platelet morphology, platelet signal transduction, platelet procoagulant activity, platelet apoptosis, platelet proteomics, and molecular biology. PMID:23653569

  19. Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator.

    PubMed

    Cao, Ning; Song, Seung Hyun; Maleki, Teimour; Shaffer, Michael; Stantz, Keith M; Cao, Minsong; Kao, Chinghai; Mendonca, Marc S; Ziaie, Babak; Ko, Song-Chu

    2016-04-01

    Over the past decades, little progress has been made to improve the extremely low survival rates in pancreatic cancer patients. Extreme hypoxia observed in pancreatic tumors contributes to the aggressive and metastatic characteristics of this tumor and can reduce the effectiveness of conventional radiation therapy and chemotherapy. In an attempt to reduce hypoxia-induced obstacles to effective radiation treatment, we used a novel device, the implantable micro-oxygen generator (IMOG), for in situ tumor oxygenation. After subcutaneous implantation of human pancreatic xenograft tumors in athymic rats, the IMOG was wirelessly powered by ultrasonic waves, producing 30 μA of direct current (at 2.5 V), which was then utilized to electrolyze water and produce oxygen within the tumor. Significant oxygen production by the IMOG was observed and corroborated using the NeoFox oxygen sensor dynamically. To test the radiosensitization effect of the newly generated oxygen, the human pancreatic xenograft tumors were subcutaneously implanted in nude mice with either a functional or inactivated IMOG device. The tumors in the mice were then exposed to ultrasonic power for 10 min, followed by a single fraction of 5 Gy radiation, and tumor growth was monitored thereafter. The 5 Gy irradiated tumors containing the functional IMOG exhibited tumor growth inhibition equivalent to that of 7 Gy irradiated tumors that did not contain an IMOG. Our study confirmed that an activated IMOG is able to produce sufficient oxygen to radiosensitize pancreatic tumors, enhancing response to single-dose radiation therapy. PMID:27002539

  20. Trefoil factor 3 stimulates human and rodent pancreatic islet beta-cell replication with retention of function.

    PubMed

    Fueger, Patrick T; Schisler, Jonathan C; Lu, Danhong; Babu, Daniella A; Mirmira, Raghavendra G; Newgard, Christopher B; Hohmeier, Hans E

    2008-05-01

    Both major forms of diabetes involve a decline in beta-cell mass, mediated by autoimmune destruction of insulin-producing cells in type 1 diabetes and by increased rates of apoptosis secondary to metabolic stress in type 2 diabetes. Methods for controlled expansion of beta-cell mass are currently not available but would have great potential utility for treatment of these diseases. In the current study, we demonstrate that overexpression of trefoil factor 3 (TFF3) in rat pancreatic islets results in a 4- to 5-fold increase in [(3)H]thymidine incorporation, with full retention of glucose-stimulated insulin secretion. This increase was almost exclusively due to stimulation of beta-cell replication, as demonstrated by studies of bromodeoxyuridine incorporation and co-immunofluorescence analysis with anti-bromodeoxyuridine and antiinsulin or antiglucagon antibodies. The proliferative effect of TFF3 required the presence of serum or 0.5 ng/ml epidermal growth factor. The ability of TFF3 overexpression to stimulate proliferation of rat islets in serum was abolished by the addition of epidermal growth factor receptor antagonist AG1478. Furthermore, TFF3-induced increases in [3H]thymidine incorporation in rat islets cultured in serum was blocked by overexpression of a dominant-negative Akt protein or treatment with triciribine, an Akt inhibitor. Finally, overexpression of TFF3 also caused a doubling of [3H]thymidine incorporation in human islets. In summary, our findings reveal a novel TFF3-mediated pathway for stimulation of beta-cell replication that could ultimately be exploited for expansion or preservation of islet beta-cell mass.

  1. A test of cirrus ice crystal scattering phase functions

    NASA Astrophysics Data System (ADS)

    Field, P. R.; Baran, A. J.; Kaye, P. H.; Hirst, E.; Greenaway, R.

    2003-07-01

    In-situ ice crystal scattering has been measured in cirrus cloud with the Small Ice Detector laser scattering probe. Using light scattered from single particles (maximum dimension ~<100 μm) at 4-10° and 20-40° we have tested ice crystal scattering phase functions for spheres, hexagonal columns, hexagonal plates, polycrystals an aggregate of columns and an analytic function. We find that phase functions that lack a pronounced 22° halo are the best representatives for the example data presented here. Spherical ice particle phase functions do not satisfy the measurements.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. Role of taxanes in pancreatic cancer

    PubMed Central

    Belli, Carmen; Cereda, Stefano; Reni, Michele

    2012-01-01

    Pancreatic cancer is one of the most deadly cancers and is characterized by a poor prognosis. Single agent gemcitabine, despite its limited activity and modest impact on disease outcome, is considered as the standard therapy in pancreatic cancer. Most of the combination regimens used in the treatment of this disease, also including the targeted agents, did not improve the outcome of patients. Also, taxanes have been tested as single agent and in combination chemotherapy, both in first line and as salvage chemotherapy, as another possible option for treating pancreatic cancer. The inclusion of taxanes in combination with gemcitabine as upfront therapy obtained promising results. Accordingly, taxanes, and above all, new generation taxanes, appear to be suitable candidates for further testing to assess their role against pancreatic cancer in various clinical settings. PMID:22969215

  7. Executive function on the Psychology Experiment Building Language tests

    PubMed Central

    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.

    2013-01-01

    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

  8. Epidemiologic and Mechanistic Associations Between Smoking and Pancreatitis

    PubMed Central

    Greer, Julia B.; Thrower, Edwin; Yadav, Dhiraj

    2015-01-01

    Opinion Statement Alcohol has long been associated with pancreatitis. Although first described more than 3 decades ago, smoking has been widely accepted as an important risk factor for all forms of pancreatitis only in the past few years. Empiric data has confirmed smoking as an independent and dose-dependent risk for both acute and chronic pancreatitis. Smoking also increases the risk of recurrences and progression of established chronic pancreatitis. The effects of smoking are enhanced in the presence of alcohol consumption. Indirect evidence suggests that smoking cessation may be beneficial in preventing disease progression. Smoking cessation can therefore be an important strategy for primary as well as secondary prevention of pancreatitis. Therefore, in addition to alcohol, physicians should routinely counsel patients for the benefits of smoking cessation. The mechanisms through which cigarette smoke triggers pathological cellular events, resulting in pancreatitis, are unresolved. Although cigarette smoke contains greater than 4000 compounds, principally nicotine and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), have been broadly studied with regard to pancreatic diseases. Both nicotine and NNK have been shown to induce morphological changes in the pancreas consistent with those seen in pancreatitis. Furthermore, nicotine affects pancreatic secretion and NNK induces premature zymogen activation, two well-known features of pancreatitis. These cigarette toxins may mediate both pro- and anti-inflammatory pathways and can induce changes in pancreatic acinar cell function at the level of transcription, leading to conditions such as thiamin deficiency and mitochondrial dysfunction. Such circumstances could leave the pancreas prone to the development of pancreatitis. This review summarizes relevant research findings and focuses on the epidemiologic links between smoking and pancreatitis, and the cellular pathways that may be

  9. 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

  10. 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

  11. 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

  12. Pancreatic paraganglioma - a rare and dangerous entity. Vascular anatomy and impact on management

    PubMed Central

    Straka, Martin; Soumarova, Renata; Migrova, Martina; Vojtek, Cyril

    2014-01-01

    Pancreatic paragangliomas are extremely rare with less than 20 cases ever described in the world literature. There is no detailed report of the vascular anatomy in this entity and its possible impact on patient management. We present a case of large pancreatic head paraganlioma in a 53-year-old woman. The tumour had a predominant arterial blood supply via both the hepatic artery and the superior mesenteric artery. Complex inflow was complemented by supplementary branches from the right renal artery. The arteriovenous communications within the lesion represented the most dangerous aspect of excision and the tumour removal was accompanied with a considerable blood loss. After pancreaticoduodenectomy, patient experienced transient elevation of liver function tests with no other identifiable cause than a change in portal haemodynamics. It is advisable that the precise knowledge of vascular anatomy in pancreatic head paraganglioma should be obtained prior to any intervention. PMID:25056378

  13. Pancreatic paraganglioma - a rare and dangerous entity. Vascular anatomy and impact on management.

    PubMed

    Straka, Martin; Soumarova, Renata; Migrova, Martina; Vojtek, Cyril

    2014-01-01

    Pancreatic paragangliomas are extremely rare with less than 20 cases ever described in the world literature. There is no detailed report of the vascular anatomy in this entity and its possible impact on patient management. We present a case of large pancreatic head paraganlioma in a 53-year-old woman. The tumour had a predominant arterial blood supply via both the hepatic artery and the superior mesenteric artery. Complex inflow was complemented by supplementary branches from the right renal artery. The arteriovenous communications within the lesion represented the most dangerous aspect of excision and the tumour removal was accompanied with a considerable blood loss. After pancreaticoduodenectomy, patient experienced transient elevation of liver function tests with no other identifiable cause than a change in portal haemodynamics. It is advisable that the precise knowledge of vascular anatomy in pancreatic head paraganglioma should be obtained prior to any intervention.

  14. 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.

  15. [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.

  16. [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

  17. 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

  18. Pancreatitis in children.

    PubMed

    Winchester, M

    1992-12-01

    The pathophysiology of pancreatic autodigestion is poorly understood. Pancreatitis affects all age groups, and the diagnosis is sometimes missed when serum amylase and lipase activities are not measured in the child with abdominal pain. Acute pancreatitis in children has become a more commonly seen condition and the causes have varied. Laboratory and radiological studies play an important role in determining the diagnosis and prognosis. Family history is important in the diagnosis of idiopathic hereditary pancreatitis. Most acute episodes resolve with supportive care, but the mortality in acute pancreatitis is currently about 15% (Hadorn et al., 1980). Endoscopic retrograde cholangiopancreatography or an endoscopic retrograde pancreatogram may be necessary to investigate relapses of pancreatitis. Chronic pancreatitis can be a life-threatening condition requiring lifetime medical management.

  19. 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

  20. 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...

  1. 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

  2. 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

  3. Low yield of unselected testing in patients with acutely abnormal liver function tests

    PubMed Central

    Chadwick, Andrew

    2015-01-01

    Objectives To audit the diagnostic yield and cost implications of the use of a ‘liver screen’ for inpatients with abnormal liver function tests. Design We performed a retrospective audit of inpatients with abnormal liver function tests. We analysed all investigations ordered including biochemistry, immunology, virology and radiology. The final diagnosis was ascertained in each case, and the diagnostic yield and cost per positive diagnosis for each investigation were calculated. Setting St Thomas’ NHS Trust. Participants All inpatients investigated for abnormal liver function tests over a 12-month period. Main outcome measures We calculated the percentage of courses due to each diagnosis, the yield of each investigation and the cost per positive diagnosis for each investigation. Results A total of 308 patients were included, and a final diagnosis was made in 224 patients (73%) on the basis of both clinical data and investigations. There was considerable heterogeneity in the tests included in an acute liver screen. History and ultrasound yielded the most diagnoses (40% and 30%, respectively). The yield of autoimmune and metabolic screens was minimal. Conclusions Our results demonstrate the low yield of unselected testing in patients with abnormal liver function tests. A thorough history, ultrasound and testing for blood-borne viruses are the cornerstones of diagnosis. Specialist input should be sought before further testing. Prospective studies to evaluate the yield and cost-effectiveness of different testing strategies are needed. PMID:26770816

  4. Fasting plasma carotenoids concentrations in Crohn's and pancreatic cancer patients compared to control subjects.

    PubMed

    Drai, J; Borel, P; Faure, H; Galabert, C; Le Moël, G; Laromiguière, M; Fayol, V

    2009-03-01

    Carotenoids are colored molecules that are widespread in the plant kingdom, but animals cannot synthesize them. Carotenes are long, apolar molecules which require fully functioning digestive processes to be absorbed properly. Hence they could be interesting markers of intestinal absorption and digestion. Indeed, only few tests are available to assess these processes and only the D-xylose tolerance test is routinely used. However D-xylose is a sugar that tests only the absorption of water-soluble compounds and it only tests duodenal absorption. In this study, we have evaluated carotenoids as markers of digestion and absorption. We compared fasting plasma carotenoids concentrations in 21 control subjects, 20 patients with Crohn's disease, and 18 patients with pancreatic cancer. Crohn's disease alters intestinal absorption while pancreatic cancer decreases pancreatic enzyme secretion thus impairing digestion. Results show that all carotenoids are significantly lower in Crohn's and cancer patients as compared to control subjects and the multifactorial analysis shows that this decrease is mostly independent of dietary intake. Interestingly, maldigestion as seen in pancreatic cancer more strongly influences plasma lutein and lycopene concentrations while malabsorption in Crohn's disease acts on other carotenoids. Thus carotenoids could be interesting alternatives for testing and following patients that are suspected of having malabsorption or maldigestion syndromes. PMID:20108210

  5. Immunotherapy of pancreatic carcinoma.

    PubMed

    Märten, Angela

    2008-05-01

    Patients with carcinoma of the exocrine pancreas have especially poor prognosis with a five-year survival rate of <1% and a median survival of 4-6 months. Pancreatic carcinoma is a systemic disease, insensitive to radiotherapy and mostly to chemotherapy. Accordingly, new treatment modalities are worth being investigated. One of the promising approaches is immunotherapy. Several phase I/II trials that have been published show interesting results, whereupon antibody-based strategies seem to fail and unspecific stimulation or vaccination with peptides look encouraging. Furthermore, phase II trials dealing with combination therapies are highly promising. One of them, a combination of chemoradiotherapy plus interferon-alpha is currently tested in a randomized phase III trial. As most of the trials had enrolled only limited numbers of patients and most of the trials were not conducted and/or reported according to the new standards it is difficult to draw final conclusions from the discussed trials. Immuno-monitoring was performed only in 40% of the discussed publications. In all cases immune responses were observed and correlation with the clinical outcome is discussed. Immunotherapy of pancreatic adenocarcinoma and especially combination therapies including immunotherapy is an up-and-coming approach and needs to be investigated in well conducted phase III randomized controlled trials accompanied by appropriate immuno-monitoring.

  6. A Single Talent Immunogenic Membrane Antigen and Novel Prognostic Predictor: voltage-dependent anion channel 1 (VDAC1) in Pancreatic Cancer

    PubMed Central

    Wang, Weibin; Zhang, Taiping; Zhao, Wenjing; Xu, Lai; Yang, Yu; Liao, Quan; Zhao, Yupei

    2016-01-01

    Immunogenic membrane antigens associated with multiple biological functions of human cancer cells, have significant value in molecule diagnosis and targeted therapy. Here we screened immunogenic membrane antigens in pancreatic cancer by immunobloting IgG purified from sera of 66 pancreatic cancer patients with membrane proteins separated from two-dimensional PAGE of human pancreatic cancer cell line SWl990, and identified voltage-dependent anion channel 1 (VDAC1) as one of the potential immunogenic membrane antigens. Further studies focusing on VDAC1 demonstrated that VDAC1 mRNA and protein were significantly expressed in the tested pancreatic cancer cell lines. VDAC1 silencing with RNAi significantly decreased cell growth, invasion and migration in the pancreatic cancer cell line Capan-1. Additionally, VDAC1 expression was upregulated in pancreatic cancer tissue compared with normal pancreas samples and patients with low VDAC1 expression had a significantly greater median survival compared to those with high expression (27.0 months vs. 17.8 months, P = 0.039). In multivariable analysis, VDAC1 staining was an independent prognostic factor for survival [(Hazard-Ratio) HR = 1.544, 95% CI = 0.794–3.0, P = 0.021]. These results demonstrated that VDAC1 may be a candidate immunogenic membrane antigen for pancreatic cancer, a potential independent prognostic marker, and an ideal drug target. PMID:27659305

  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.

  8. [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.

  9. Item Response Changes on Multiple-Choice Tests as a Function of Test Anxiety.

    ERIC Educational Resources Information Center

    Green, Kathy

    Item response changing as a function of test anxiety was investigated. Seventy graduate students enrolled in a basic statistics course completed 73 multiple-choice items on the course content and the Test Anxiety Scale (TAS). The TAS consisted of 25 items that students indicated were descriptive (true) or not descriptive (false) of themselves.…

  10. Elevated amylase creatinine clearance ratio and normal serum amylase levels in chronic relapsing pancreatitis after partial pancreatectomy.

    PubMed

    Cattau, E L; Garcia-Torres, F

    1980-12-01

    A 29-year-old woman admitted for alcohol detoxification five years after a 90% distal pancreatectomy for chronic pancreatitis had abdominal pain similar to that associated with preoperative pancreatitis. Although her clinical course was consistent with recurrent pancreatitis, the serum amylase level remained normal, but the amylase creatinine clearance ratio became elevated and then returned to normal, paralleling her clinical course. The ACCR may be a useful laboratory method in diagnosing chronic recurrent pancreatitis in patients with decreased functional pancreatic tissue.

  11. 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.

  12. Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta.

    PubMed

    Shih, David Q; Heimesaat, Markus; Kuwajima, Satoru; Stein, Roland; Wright, Christopher V E; Stoffel, Markus

    2002-03-19

    Defects in pancreatic beta-cell function contribute to the development of type 2 diabetes, a polygenic disease that is characterized by insulin resistance and compromised insulin secretion. Hepatocyte nuclear factors (HNFs) -1alpha, -3beta, -4alpha, and Pdx-1 contribute in the complex transcriptional circuits within the pancreas that are involved in beta-cell development and function. In mice, a heterozygous mutation in Pdx-1 alone, but not Hnf-1alpha(+/-), Hnf-3beta(+/-), or Hnf-4alpha(+/-), causes impaired glucose-stimulated insulin secretion in mice. To investigate the possible functional relationships between these transcription factors on beta-cell activity in vivo, we generated mice with the following combined heterozygous mutations: Pdx-1(+/-)/Hnf-1alpha(+/-), Pdx-1(+/-)/Hnf-3beta(+/-), Pdx-1(+/-)/Hnf-4alpha(+/-), Hnf-1alpha(+/-)/Hnf-4alpha(+/-), and Hnf-3beta(+/-)/Hnf-4alpha(+/-). The greatest loss in function was in combined heterozygous null alleles of Pdx-1 and Hnf-1alpha (Pdx-1(+/-)/Hnf-1alpha(+/-)), or Pdx-1 and Hnf-3beta (Pdx-1(+/-)/Hnf-3beta(+/-)). Both double mutants develop progressively impaired glucose tolerance and acquire a compromised first- and second-phase insulin secretion profile in response to glucose compared with Pdx-1(+/-) mice alone. The loss in beta-cell function in Pdx-1(+/-)/Hnf-3beta(+/-) mice was associated with decreased expression of Nkx-6.1, glucokinase (Gck), aldolase B (aldo-B), and insulin, whereas Nkx2.2, Nkx-6.1, Glut-2, Gck, aldo-B, the liver isoform of pyruvate kinase, and insulin expression was reduced in Pdx-1(+/-)/Hnf-1alpha(+/-) mice. The islet cell architecture was also abnormal in Pdx-1(+/-)/Hnf-3beta(+/-) and Pdx-1(+/-)/Hnf-1alpha(+/-) mice, with glucagon-expressing cells scattered throughout the islet, a defect that may be connected to decreased E-cadherin expression. Our data suggest that functional interactions between key islet regulatory factors play an important role in maintaining islet architecture and

  13. 20 CFR 718.103 - Pulmonary function tests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... of the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). The report shall also provide the FEV1/FVC ratio, expressed as a percentage. If the maximum voluntary ventilation... the results of the FEV1. (b) All pulmonary function test results submitted in connection with a...

  14. 20 CFR 718.103 - Pulmonary function tests.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... of the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). The report shall also provide the FEV1/FVC ratio, expressed as a percentage. If the maximum voluntary ventilation... the results of the FEV1. (b) All pulmonary function test results submitted in connection with a...

  15. 20 CFR 718.103 - Pulmonary function tests.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... of the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). The report shall also provide the FEV1/FVC ratio, expressed as a percentage. If the maximum voluntary ventilation... the results of the FEV1. (b) All pulmonary function test results submitted in connection with a...

  16. 20 CFR 718.103 - Pulmonary function tests.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... of the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). The report shall also provide the FEV1/FVC ratio, expressed as a percentage. If the maximum voluntary ventilation... the results of the FEV1. (b) All pulmonary function test results submitted in connection with a...

  17. 20 CFR 718.103 - Pulmonary function tests.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... of the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). The report shall also provide the FEV1/FVC ratio, expressed as a percentage. If the maximum voluntary ventilation... the results of the FEV1. (b) All pulmonary function test results submitted in connection with a...

  18. 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

  19. [The general practitioner and abnormal liver function tests].

    PubMed

    Hallez, R

    1997-09-01

    In case of abnormal liver function tests, it's necessary to distinguish different situations, starting from this first data. We will successively consider: the high and moderate acute increases of aminotransferase, the chronic increases of aminotransferase, the isolated cholestase picture and the isolated increases of gamma GT or of bilirubine. We will finish with a partial survey about drug-induced liver diseases.

  20. 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

  1. MUSCULOSKELETAL SCREENING AND FUNCTIONAL TESTING: CONSIDERATIONS FOR BASKETBALL ATHLETES

    PubMed Central

    Markwick, William J.

    2016-01-01

    Background and Purpose Youth participation in basketball is on the rise, with basketball one of the top five participation sports in Australia. With increased participation there is a need for greater awareness of the importance of the pre-participation examination, including musculoskeletal screening and functional performance testing as part of a multidisciplinary approach to reducing the risk for future injuries. As majority of all basketball injuries affect the lower extremities, pre-participation musculoskeletal screening and functional performance testing should assess fundamental movement qualities throughout the kinetic chain with an emphasis on lower extremity force characteristics, specifically eccentric loading tasks. Thus, the purpose of this clinical commentary is to review the existing literature elucidating pre-participation musculoskeletal screening and functional performance tests that can be used as a framework for rehabilitation professionals in assessing basketball athletes’ readiness to safely perform the movement demands of their sport. Methods Relevant articles published between 2000 and 2016 using the search terms ‘musculoskeletal screening’, ‘functional testing’, ‘youth athletes’, and ‘basketball’ were identified using MEDLINE. From a basketball-specific perspective, several relevant musculoskeletal assessments were identified, including: the Functional Hop Test Combination, the Landing Error Scoring System, the Tuck Jump Assessment, the Weight-Bearing Lunge Test, and the Star Excursion Balance Test. Each of these assessments creates movement demands that allow for easy identification of inefficient and/or compensatory movement tendencies. A basic understanding of musculoskeletal deficits including bilateral strength and flexibility imbalances, lower crossed syndrome, and dominance-related factors are key components in determination of injury risk. Discussion Assessment of sport-specific movement demands through

  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. Behavioral tests of hippocampal function: simple paradigms complex problems.

    PubMed

    Gerlai, R

    2001-11-01

    Behavioral tests have become important tools for the analysis of functional effects of induced mutations in transgenic mice. However, depending on the type of mutation and several experimental parameters, false positive or negative findings may be obtained. Given the fact that molecular neurobiologists now make increasing use of behavioral paradigms in their research, it is imperative to revisit such problems. In this review three tests, T-maze spontaneous alternation task (T-CAT), Context dependent fear conditioning (CDFC), and Morris water maze (MWM) sensitive to hippocampal function, serve as illustrative examples for the potential problems. Spontaneous alternation tests are sometimes flawed because the handling procedure makes the test dependent on fear rather than exploratory behavior leading to altered alternation rates independent of hippocampal function. CDFC can provide misleading results because the context test, assumed to be a configural task dependent on the hippocampus, may have a significant elemental, i.e. cued, component. MWM may pose problems if its visible platform task is disproportionately easier for the subjects to solve than the hidden platform task, if the order of administration of visible and hidden platform tasks is not counterbalanced, or if inappropriate parameters are measured. Without attempting to be exhaustive, this review discusses such experimental problems and gives examples on how to avoid them.

  4. 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.

  5. 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

  6. 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

  7. PDX-1 (pancreatic/duodenal homeobox-1 protein 1).

    PubMed

    Pedica, F; Beccari, S; Pedron, S; Montagna, L; Piccoli, P; Doglioni, C; Chilosi, M

    2014-12-01

    The homeodomain-containing transcription factor pancreatic duodenal homeobox 1 (PDX-1) plays a key role in pancreatic development and β-cell function. It is a major regulator of transcription in pancreatic cells, and transactivates the insulin gene by binding to a specific DNA motif in its promoter region. Glucose also regulates insulin gene transcription through PDX-1. It has been shown that PDX-1 is required for maintaining pancreatic islet functions by activating gene expression and has a dual role in pancreatic development. It initially contributes to pancreatic formation during embryogenesis and subsequently regulates the pancreatic islet cell physiology in mature islet cells. Because of this key role in the embryologic development of the pancreas, PDX-1 expression has been investigated in pancreatic cancer cell lines and human tumors. Moreover, a few reports have described expression of PDX-1 in other human neoplasms and have investigated its potential role in differential diagnosis, but data on normal human tissues are lacking. Understanding the molecular mechanisms of pancreas formation, and especially the function of PDX-1, may contribute to the improved treatment and prevention of debilitating diseases such as diabetes, insulinomas and pancreatic carcinomas. Nevertheless, further studies are needed concerning its possible application in routine practice.

  8. 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 ...

  9. 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 ...

  10. 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 ...

  11. Progesterone receptor membrane component 1 is a functional part of the glucagon-like peptide-1 (GLP-1) receptor complex in pancreatic β cells.

    PubMed

    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

    2014-11-01

    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.

  12. 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

  13. Enhanced glucose-induced intracellular signaling promotes insulin hypersecretion: pancreatic beta-cell functional adaptations in a model of genetic obesity and prediabetes.

    PubMed

    Irles, Esperanza; Ñeco, Patricia; Lluesma, Mónica; Villar-Pazos, Sabrina; Santos-Silva, Junia Carolina; Vettorazzi, Jean F; Alonso-Magdalena, Paloma; Carneiro, Everardo M; Boschero, Antonio C; Nadal, Ángel; Quesada, Ivan

    2015-03-15

    Obesity is associated with insulin resistance and is known to be a risk factor for type-2 diabetes. In obese individuals, pancreatic beta-cells try to compensate for the increased insulin demand in order to maintain euglycemia. Most studies have reported that this adaptation is due to morphological changes. However, the involvement of beta-cell functional adaptations in this process needs to be clarified. For this purpose, we evaluated different key steps in the glucose-stimulated insulin secretion (GSIS) in intact islets from female ob/ob obese mice and lean controls. Obese mice showed increased body weight, insulin resistance, hyperinsulinemia, glucose intolerance and fed hyperglycemia. Islets from ob/ob mice exhibited increased glucose-induced mitochondrial activity, reflected by enhanced NAD(P)H production and mitochondrial membrane potential hyperpolarization. Perforated patch-clamp examination of beta-cells within intact islets revealed several alterations in the electrical activity such as increased firing frequency and higher sensitivity to low glucose concentrations. A higher intracellular Ca(2+) mobilization in response to glucose was also found in ob/ob islets. Additionally, they displayed a change in the oscillatory pattern and Ca(2+) signals at low glucose levels. Capacitance experiments in intact islets revealed increased exocytosis in individual ob/ob beta-cells. All these up-regulated processes led to increased GSIS. In contrast, we found a lack of beta-cell Ca(2+) signal coupling, which could be a manifestation of early defects that lead to beta-cell malfunction in the progression to diabetes. These findings indicate that beta-cell functional adaptations are an important process in the compensatory response to obesity.

  14. 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…

  15. 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

  16. 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

  17. 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

  18. Maturation of Human Embryonic Stem Cell–Derived Pancreatic Progenitors Into Functional Islets Capable of Treating Pre-existing Diabetes in Mice

    PubMed Central

    Rezania, Alireza; Bruin, Jennifer E.; Riedel, Michael J.; Mojibian, Majid; Asadi, Ali; Xu, Jean; Gauvin, Rebecca; Narayan, Kavitha; Karanu, Francis; O’Neil, John J.; Ao, Ziliang; Warnock, Garth L.

    2012-01-01

    Diabetes is a chronic debilitating disease that results from insufficient production of insulin from pancreatic β-cells. Islet cell replacement can effectively treat diabetes but is currently severely limited by the reliance upon cadaveric donor tissue. We have developed a protocol to efficiently differentiate commercially available human embryonic stem cells (hESCs) in vitro into a highly enriched PDX1+ pancreatic progenitor cell population that further develops in vivo to mature pancreatic endocrine cells. Immature pancreatic precursor cells were transplanted into immunodeficient mice with streptozotocin-induced diabetes, and glycemia was initially controlled with exogenous insulin. As graft-derived insulin levels increased over time, diabetic mice were weaned from exogenous insulin and human C-peptide secretion was eventually regulated by meal and glucose challenges. Similar differentiation of pancreatic precursor cells was observed after transplant in immunodeficient rats. Throughout the in vivo maturation period hESC-derived endocrine cells exhibited gene and protein expression profiles that were remarkably similar to the developing human fetal pancreas. Our findings support the feasibility of using differentiated hESCs as an alternative to cadaveric islets for treating patients with diabetes. PMID:22740171

  19. 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

  20. [Interventional neuroradiology. Drug treatment, monitoring and function tests].

    PubMed

    Laurent, A; Gobin, Y P; Launay, F; Aymard, A; Casasco, A; Merland, J J

    1994-04-23

    Specialized monitoring as well as function tests and drug therapy play an ever growing role in neuroradiological procedures. The particular route of administration and the territories involved in neuroradiology require special precautions. Anaesthesia must enable the operators to monitor the central nervous system since the patients must remain totally immobilized for several hours. Catheterization is made safe by careful asepsia and antibiotic prophylaxis and by preventing embolic events, particularly in neuro-cervico-facial interventions where an anticoagulant protocol is important. Arterial spasms can be prevented or cured with calcium inhibitors. The safety of the procedure itself is guaranteed by various function tests including sensitivity to ischaemia using anaesthetic barbiturates, controlled clampings or the lidocaine test. Undesirable effects of both emboli (e.g. toxicity of cyanoacrylate glue) and embolization (e.g. subsequent venous thrombosis) can be prevented by adapted anti-inflammatory drugs. Herein, we describe the routine monitoring conditions, drugs prescribed and function tests performed at the Therapeutic Angiography Department of the Lariboisière Hospital, Paris.

  1. Nutrition in acute pancreatitis.

    PubMed

    Nompleggi, D J

    1999-08-01

    Pancreatitis is a common disorder. Numerous factors have been implicated in the pathogenesis of acute and chronic pancreatitis, but the exact mechanisms of these conditions are still poorly understood. Depending on the cause of the disorder, patients who have pancreatitis are usually not malnourished and are able to eat within 5 to 7 days of disease onset. In these patients, nutritional support is unnecessary. However, severe disease induces a catabolic state similar to that seen in trauma and sepsis, resulting in rapid weight loss and increased morbidity and mortality. Thus, vigorous nutritional support may be useful in the treatment of severe pancreatitis. Studies have shown that parenteral and enteral nutritional support are well tolerated and can maintain or improve nutritional status in patients with pancreatitis. This article reviews nutritional assessment and therapy in pancreatitis.

  2. Testing the link between functional diversity and ecosystem functioning in a Minnesota grassland experiment.

    PubMed

    Clark, Christopher M; Flynn, Dan F B; Butterfield, Bradley J; Reich, Peter B

    2012-01-01

    The functional diversity of a community can influence ecosystem functioning and reflects assembly processes. The large number of disparate metrics used to quantify functional diversity reflects the range of attributes underlying this concept, generally summarized as functional richness, functional evenness, and functional divergence. However, in practice, we know very little about which attributes drive which ecosystem functions, due to a lack of field-based tests. Here we test the association between eight leading functional diversity metrics (Rao's Q, FD, FDis, FEve, FDiv, convex hull volume, and species and functional group richness) that emphasize different attributes of functional diversity, plus 11 extensions of these existing metrics that incorporate heterogeneous species abundances and trait variation. We assess the relationships among these metrics and compare their performances for predicting three key ecosystem functions (above- and belowground biomass and light capture) within a long-term grassland biodiversity experiment. Many metrics were highly correlated, although unique information was captured in FEve, FDiv, and dendrogram-based measures (FD) that were adjusted by abundance. FD adjusted by abundance outperformed all other metrics in predicting both above- and belowground biomass, although several others also performed well (e.g. Rao's Q, FDis, FDiv). More generally, trait-based richness metrics and hybrid metrics incorporating multiple diversity attributes outperformed evenness metrics and single-attribute metrics, results that were not changed when combinations of metrics were explored. For light capture, species richness alone was the best predictor, suggesting that traits for canopy architecture would be necessary to improve predictions. Our study provides a comprehensive test linking different attributes of functional diversity with ecosystem function for a grassland system.

  3. Non-invasive pulmonary function test on Morquio Patients

    PubMed Central

    Kubaski, Francyne; Tomatsu, Shunji; Patel, Pravin; Shimada, Tsutomu; Xie, Li; Yasuda, Eriko; Mason, Robert; Mackenzie, William G.; Theroux, Mary; Bober, Michael B.; Oldham, Helen M.; Orii, Tadao; Shaffer, Thomas H.

    2015-01-01

    In clinical practice, respiratory function tests are difficult to perform in Morquio syndrome patients due to their characteristic skeletal dysplasia, small body size and lack of cooperation of young patients, where in some cases, conventional spirometry for pulmonary function is too challenging. To establish feasible clinical pulmonary endpoints and determine whether age impacts lung function in Morquio patients non-invasive pulmonary tests and conventional spirometry were evaluated. The non-invasive pulmonary tests: impulse oscillometry system, pneumotachography, and respiratory inductance plethysmography in conjunction with conventional spirometry were evaluated in twenty-two Morquio patients (18 Morquio A and 4 Morquio B) (7 males), ranging from 3 and 40 years of age. Twenty-two patients were compliant with non-invasive tests (100%) with exception of IOS (81.8%–18 patients). Seventeen patients (77.3%) were compliant with spirometry testing. All subjects had normal vital signs at rest including > 95% oxygen saturation, end tidal CO2 (38–44 mmHg), and age-appropriate heart rate (mean=98.3, standard deviation=19) (two patients were deviated). All patients preserved normal values in impulse oscillometry system, pneumotachography, and respiratory inductance plethysmography, although predicted forced expiratory volume total (72.8 ± 6.9 SE%) decreased with age and was below normal; phase angle (35.5 ± 16.5 Degrees), %Rib Cage (41.6 ± 12.7%), resonant frequency, and forced expiratory volume in one second/forced expiratory volume total (110.0 ± 3.2 SE%) were normal and not significantly impacted by age. The proposed non-invasive pulmonary function tests are able to cover a greater number of patients (young patients and/or wheel-chair bound), thus providing a new diagnostic approach for the assessment of lung function in Morquio syndrome which in many cases may be difficult to evaluate. Morquio patients studied herein demonstrated no clinical or functional signs

  4. Non-invasive pulmonary function test on Morquio patients.

    PubMed

    Kubaski, Francyne; Tomatsu, Shunji; Patel, Pravin; Shimada, Tsutomu; Xie, Li; Yasuda, Eriko; Mason, Robert; Mackenzie, William G; Theroux, Mary; Bober, Michael B; Oldham, Helen M; Orii, Tadao; Shaffer, Thomas H

    2015-08-01

    In clinical practice, respiratory function tests are difficult to perform in Morquio syndrome patients due to their characteristic skeletal dysplasia, small body size and lack of cooperation of young patients, where in some cases, conventional spirometry for pulmonary function is too challenging. To establish feasible clinical pulmonary endpoints and determine whether age impacts lung function in Morquio patients non-invasive pulmonary tests and conventional spirometry were evaluated. The non-invasive pulmonary tests: impulse oscillometry system, pneumotachography, and respiratory inductance plethysmography in conjunction with conventional spirometry were evaluated in twenty-two Morquio patients (18 Morquio A and 4 Morquio B) (7 males), ranging from 3 to 40 years of age. Twenty-two patients were compliant with non-invasive tests (100%) with the exception of IOS (81.8%-18 patients). Seventeen patients (77.3%) were compliant with spirometry testing. All subjects had normal vital signs at rest including >95% oxygen saturation, end tidal CO2 (38-44 mmHg), and age-appropriate heart rate (mean=98.3, standard deviation=19) (two patients were deviated). All patients preserved normal values in the impulse oscillometry system, pneumotachography, and respiratory inductance plethysmography, although predicted forced expiratory total (72.8±6.9 SE%) decreased with age and was below normal; phase angle (35.5±16.5°), %rib cage (41.6±12.7%), resonant frequency, and forced expiratory volume in 1 s/forced expiratory volume total (110.0±3.2 SE%) were normal and not significantly impacted by age. The proposed non-invasive pulmonary function tests are able to cover a greater number of patients (young patients and/or wheel-chair bound), thus providing a new diagnostic approach for the assessment of lung function in Morquio syndrome which in many cases may be difficult to evaluate. Morquio patients studied herein demonstrated no clinical or functional signs of restrictive and

  5. [The prognostic value of liver function tests--clinical aspects, laboratory chemical parameters and quantitative function tests].

    PubMed

    Wahlländer, A; Beuers, U

    1990-05-01

    In view of increasing therapeutic possibilities interest focuses on prognosis of liver cirrhosis. Until nowadays studies on prognosis revealed significant importance only for some parameters: Ascites, encephalopathy and portal hypertension as signs of decompensation, bilirubin, albumin and prothrombin time as laboratory indices of decreasing liver function. The commonly used Child-Pugh-score is based on these parameters and allows a reasonable classification of diseased patients. Cholestasis and inflammation seem to be of minor prognostic importance. Assessment of liver function by quantitative tests is desirable (e.g. aminopyrine breath test, bile acids). The prognostic value, however, has not yet been proven in large studies. Use of these tests should therefore be restricted to studies (prognosis, therapy, indication to liver transplantation).

  6. 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

  7. 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

  8. 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

  9. Smoking and Pancreatic Disease.

    PubMed

    Edderkaoui, Mouad; Thrower, Edwin

    2013-11-01

    Smoking is a major risk factor for chronic pancreatitis and pancreatic cancer. However, the mechanisms through which it causes the diseases remain unknown. In the present manuscript we reviewed the latest knowledge gained on the effect of cigarette smoke and smoking compounds on cell signaling pathways mediating both diseases. We also reviewed the effect of smoking on the pancreatic cell microenvironment including inflammatory cells and stellate cells.

  10. Role of cholecystokinin in pancreatic adaptation to massive enterectomy.

    PubMed Central

    Watanapa, P; Egan, M; Deprez, P H; Calam, J; Sarraf, C E; Alison, M R; Williamson, R C

    1992-01-01

    Since pancreatic adaptation to massive proximal small bowel resection (PSBR) may be modulated through cholecystokinin (CCK) secretion, we tested the effect of the CCK antagonist CR-1409 on this response. Male Wistar rats (n = 72) weighing 220-225 g were randomised to receive either PSBR or transection/resuture followed by saline or CR-1409 (12 mg/kg daily subcutaneously). Rats were killed one, two, and three weeks post-operatively, at which time blood was obtained for CCK assay and the pancreas was assessed for proliferative activity by three parameters: nucleic acid and protein content, bromode-oxyuridine (BrdUrd) labelling index, and proliferating cell nuclear antigen (PCNA) expression. PSBR increased plasma CCK concentration by 83-102% at 1-3 weeks, irrespective of CR-1409 administration. Total pancreatic DNA content per 100 g body weight increased by 34% at two weeks (p less than 0.05) and by 82% at three weeks (p less than 0.05), while RNA content increased by 60% and 178% (p less than 0.001) and protein content by 20% and 57% (p less than 0.05). PSBR increased the BrdUrd labelling index and the percentage of PCNA immunoreactive cells. CR-1409 completely abolished this proliferative response and also prevented the rise in nucleic acid and protein contents. Apart from growth stimulation, PSBR also enhanced pancreatic exocrine function, as shown by ultrastructural evidence of an appreciable decrease in zymogen granules; CR-1409 also inhibited this functional effect of hypercholecystokininaemia. The results confirm the tropic role of CCK after PSBR, and CR-1409 prevents this pancreatic adaptation. Images Figure 6 Figure 7 Figure 8 PMID:1644338

  11. Dynamic testing in the evaluation of male gonadal function.

    PubMed

    De Martino, M U; Pastore, R; Caprio, M; Frajese, G; Fabbri, A

    2003-01-01

    The maturation and physiologic functions of male sexual apparatus are under the control of the hypothalamic-pituitary-gonadal (HPG) axis. The determination of gonadotropins and testosterone as secretory products of pituitary and gonads, respectively, represents the first step in the evaluation of male sexual function and the diagnosis of disorders in male reproductive axis. However, there are several clinical situations that require a dynamic evaluation of this system and the measurement of basal gonadotropins and testosterone must be combined with specific dynamic tests. These mainly consist in GnRH stimulation, which evaluates the endocrine reserve capacity of the pituitary, and human chorionic gonadotropin (hCG) stimulation, which is used in the assessment of Leydig cells activity. The paper illustrates the technical aspects, the normal/pathological responses and the role of these two tests in assessing the male HPG axis in respect to different clinical diagnostic queries.

  12. Clinical, anthropometric and laboratory nutritional markers of pancreatic exocrine insufficiency: Prevalence and diagnostic use.

    PubMed

    Lindkvist, Björn; Phillips, Mary E; Domínguez-Muñoz, J Enrique

    2015-01-01

    Pancreatic exocrine insufficiency (PEI) frequently occurs secondary to exocrine pancreatic disease (e.g. chronic pancreatitis, cystic fibrosis, cancer) or pancreatic/gastrointestinal surgery, resulting in the maldigestion of nutrients and consequently malnutrition. Pancreatic enzyme replacement therapy (PERT) is the cornerstone of PEI management. Despite its clinical relevance, the diagnosis of PEI in clinical practice is challenging, as the current gold standard test is cumbersome, and alternatives have limited availability or accuracy. There is a need for accurate and easily applicable diagnostic modalities. We review the prevalence of clinical symptoms and changes in anthropometric measurements and laboratory nutritional markers indicative of malnutrition in patients with PEI, and the relevance of these findings in diagnosing PEI and monitoring PERT efficacy. Based on limited available evidence, assessment of clinical symptoms, body weight, body mass index and other anthropometric parameters are not sensitive methods for PEI diagnosis, owing to high variability and multiple confounding factors, but appear useful in monitoring PERT efficacy. Limited evidence precludes strong recommendations but suggests that serum levels of vitamin E, magnesium, and plasma proteins, notably retinol binding protein, albumin, and prealbumin, may have diagnostic utility in PEI. Studies show that assessment of changes in these and other nutritional parameters is helpful in monitoring PERT efficacy. Further research is needed to confirm the diagnostic accuracy of these parameters for PEI. Until such data are available, a nutritional evaluation including circulating vitamin E, magnesium, retinol binding protein, albumin, and prealbumin may be used to evaluate the probability of PEI in clinical practice when reliable pancreatic function tests are not available. PMID:26243045

  13. 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

  14. Test Protocols for Advanced Inverter Interoperability Functions - Appendices

    SciTech Connect

    Johnson, Jay Dean; Gonzalez, Sigifredo; Ralph, Mark E.; Ellis, Abraham; Broderick, Robert Joseph

    2013-11-01

    Distributed energy resources (DER) such as photovoltaic (PV) systems, when deployed in a large scale, are capable of influencing significantly the operation of power systems. Looking to the future, stakeholders are working on standards to make it possible to manage the potentially complex interactions between DER and the power system. In 2009, the Electric Power Research Institute (EPRI), Sandia National Laboratories (SNL) with the U.S. Department of Energy (DOE), and the Solar Electric Power Association (SEPA) initiated a large industry collaborative to identify and standardize definitions for a set of DER grid support functions. While the initial effort concentrated on grid-tied PV inverters and energy storage systems, the concepts have applicability to all DER. A partial product of this on-going effort is a reference definitions document (IEC TR 61850-90-7, Object models for power converters in distributed energy resources (DER) systems) that has become a basis for expansion of related International Electrotechnical Commission (IEC) standards, and is supported by US National Institute of Standards and Technology (NIST) Smart Grid Interoperability Panel (SGIP). Some industry-led organizations advancing communications protocols have also embraced this work. As standards continue to evolve, it is necessary to develop test protocols to independently verify that the inverters are properly executing the advanced functions. Interoperability is assured by establishing common definitions for the functions and a method to test compliance with operational requirements. This document describes test protocols developed by SNL to evaluate the electrical performance and operational capabilities of PV inverters and energy storage, as described in IEC TR 61850-90-7. While many of these functions are not now required by existing grid codes or may not be widely available commercially, the industry is rapidly moving in that direction. Interoperability issues are already apparent as

  15. Test Protocols for Advanced Inverter Interoperability Functions – Main Document

    SciTech Connect

    Johnson, Jay Dean; Gonzalez, Sigifredo; Ralph, Mark E.; Ellis, Abraham; Broderick, Robert Joseph

    2013-11-01

    Distributed energy resources (DER) such as photovoltaic (PV) systems, when deployed in a large scale, are capable of influencing significantly the operation of power systems. Looking to the future, stakeholders are working on standards to make it possible to manage the potentially complex interactions between DER and the power system. In 2009, the Electric Power Research Institute (EPRI), Sandia National Laboratories (SNL) with the U.S. Department of Energy (DOE), and the Solar Electric Power Association (SEPA) initiated a large industry collaborative to identify and standardize definitions for a set of DER grid support functions. While the initial effort concentrated on grid-tied PV inverters and energy storage systems, the concepts have applicability to all DER. A partial product of this on-going effort is a reference definitions document (IEC TR 61850-90-7, Object models for power converters in distributed energy resources (DER) systems) that has become a basis for expansion of related International Electrotechnical Commission (IEC) standards, and is supported by US National Institute of Standards and Technology (NIST) Smart Grid Interoperability Panel (SGIP). Some industry-led organizations advancing communications protocols have also embraced this work. As standards continue to evolve, it is necessary to develop test protocols to independently verify that the inverters are properly executing the advanced functions. Interoperability is assured by establishing common definitions for the functions and a method to test compliance with operational requirements. This document describes test protocols developed by SNL to evaluate the electrical performance and operational capabilities of PV inverters and energy storage, as described in IEC TR 61850-90-7. While many of these functions are not currently required by existing grid codes or may not be widely available commercially, the industry is rapidly moving in that direction. Interoperability issues are already

  16. 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

  17. 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

  18. Alterations in cardiovascular autonomic function tests in idiopathic hyperhidrosis.

    PubMed

    De Marinis, Milena; Colaizzo, Elisa; Petrelli, Rosa Anna Nives; Santilli, Valter

    2012-04-01

    We performed cardiovascular autonomic function tests to assess sympathetic and parasympathetic functions in patients with idiopathic hyperhidrosis. We studied 35 patients with idiopathic hyperhidrosis and 35 age- and sex-matched controls. A thermoregulatory sweat test (TST) was performed in all subjects. Sweating was qualitatively (Minor's test at 22°C) and quantitatively (skin conductance) evaluated. Orthostatism, tilt to 65°, cold pressor test, deep breathing, Valsalva maneuver and hyperventilation were performed in patients and controls. A greater fall in blood pressure values was observed in patients than in controls in the upright tests (p<0.05). In particular, postural hypotension was present in a subgroup of patients (34%), in whom changes in lying-to-standing blood pressure and heart rate were greater (p<0.001) than those of the remaining patients. The TST revealed that the total body sweat rate (ml/cm(2)/min) was more pronounced in patients with postural hypotension (p<0.001) than in the other patients and controls. The skin conductance values of patients with postural hypotension were higher (p<0.001) than those of the remaining patients. A positive correlation was found between skin conductance values and postural hypotension. Dehydration and poor water intake may play a role in postural hypotension in patients with severe hyperhidrosis and pronounced thermoregulatory sweating. A significantly marked increase in parasympathetic function was observed in patients. Responses to deep breathing, Valsalva maneuver and hyperventilation were significantly greater in patients (p<0.001) than in controls. Idiopathic hyperhidrosis seems to be a complex dysfunction that involves autonomic pathways other than those related to sweating.

  19. Half-Antibody Functionalized Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery to Carcinoembryonic Antigen (CEA) Presenting Pancreatic Cancer Cells

    PubMed Central

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

    2010-01-01

    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-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 non-targeted nanoparticles. PMID:20394436

  20. 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

  1. Lung function tests in clinical decision-making.

    PubMed

    Puente Maestú, Luis; García de Pedro, Julia

    2012-05-01

    In this article, we review the utility of the most common lung function tests (spirometry, reversibility test, peak expiratory flow, lung volumes, maximal respiratory pressure, carbon monoxide transference, arterial blood gas, 6-minute walk test and desaturation with exercise and ergospirometry) related to the most frequent pathologies (dyspnea of undetermined origin, chronic cough, asthma, COPD, neuromuscular diseases, interstitial diseases, pulmonary vascular diseases, pre-operative evaluation and disability evaluation). Our analysis has been developed from the perspective of decision-making, clinical interpretation or aspects that the physician should take into account with their use. Consequently, the paper does not deal with aspects of quality, technique or equipment, with the exception of when regarding costs as we believe that this is an important element in the decision-making process. The document is extensively supported by references from the literature.

  2. NICMOS Filter Wheel/Mechanisms Mini-Functional Test

    NASA Astrophysics Data System (ADS)

    Schneider, Glenn

    2001-07-01

    This is an early engineering test to verify the aliveness, functionality, operability, and electro-mechanical calibration of the NICMOS filter wheel motors and assembly. This is the FIRST use of the NICMOS filter wheel mechanisms since they were disabled by ground command in January, 1999. This test has been designed to obviate concerns over possible deformation or breakage of the fitter wheel "soda-straw" shafts due to excess rotational drag torque and/or bending moments which may be imparted due to changes in the dewar metrology from warm-up/cool-down. This test should be executed after the VCS {and filter wheel housing} has reached and approximately equilibrated to its nominal Cycle 11 operating temperature.

  3. 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

  4. 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

  5. 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

  6. Pancreatic beta cell function following liraglutide-augmented weight loss in individuals with prediabetes: analysis of a randomised, placebo-controlled study

    PubMed Central

    Liu, Alice; Ariel, Danit; Abbasi, Fahim; Lamendola, Cindy; Grove, Kaylene; Tomasso, Vanessa; Reaven, Gerald

    2016-01-01

    Aims/hypothesis Liraglutide can modulate insulin secretion by directly stimulating beta cells or indirectly through weight loss and enhanced insulin sensitivity. Recently, we showed that liraglutide treatment in overweight individuals with prediabetes (impaired fasting glucose and/or impaired glucose tolerance) led to greater weight loss (−7.7% vs −3.9%) and improvement in insulin resistance compared with placebo. The current study evaluates the effects on beta cell function of weight loss augmented by liraglutide compared with weight loss alone. Methods This was a parallel, randomised study conducted in a single academic centre. Both participants and study administrators were blinded to treatment assignment. Individuals who were 40–70 years old, overweight (BMI 27–40 kg/m2) and with prediabetes were randomised (via a computerised system) to receive liraglutide (n = 35) or matching placebo (n = 33), and 49 participants were analysed. All were instructed to follow an energy-restricted diet. Primary outcome was insulin secretory function, which was evaluated in response to graded infusions of glucose and day-long mixed meals. Results Liraglutide treatment (n = 24) significantly (p ≤0.03) increased the insulin secretion rate (% mean change [95% CI]; 21% [12, 31] vs −4% [−11, 3]) and pancreatic beta cell sensitivity to intravenous glucose (229% [161, 276] vs −0.5% (−15, 14]), and decreased insulin clearance rate (−3.5% [−11, 4] vs 8.2 [0.2, 16]) as compared with placebo (n = 25). The liraglutide-treated group also had significantly (p ≤0.03) lower day-long glucose (−8.2% [−11, −6] vs −0.1 [−3, 2]) and NEFA concentrations (−14 [−20, −8] vs −2.1 [−10, 6]) following mixed meals, whereas day-long insulin concentrations did not significantly differ as compared with placebo. In a multivariate regression analysis, weight loss was associated with a decrease in insulin secretion rate and day-long glucose and insulin concentrations in

  7. 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

  8. 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

  9. A computer vision based candidate for functional balance test.

    PubMed

    Nalci, Alican; Khodamoradi, Alireza; Balkan, Ozgur; Nahab, Fatta; Garudadri, Harinath

    2015-08-01

    Balance in humans is a motor skill based on complex multimodal sensing, processing and control. Ability to maintain balance in activities of daily living (ADL) is compromised due to aging, diseases, injuries and environmental factors. Center for Disease Control and Prevention (CDC) estimate of the costs of falls among older adults was $34 billion in 2013 and is expected to reach $54.9 billion in 2020. In this paper, we present a brief review of balance impairments followed by subjective and objective tools currently used in clinical settings for human balance assessment. We propose a novel computer vision (CV) based approach as a candidate for functional balance test. The test will take less than a minute to administer and expected to be objective, repeatable and highly discriminative in quantifying ability to maintain posture and balance. We present an informal study with preliminary data from 10 healthy volunteers, and compare performance with a balance assessment system called BTrackS Balance Assessment Board. Our results show high degree of correlation with BTrackS. The proposed system promises to be a good candidate for objective functional balance tests and warrants further investigations to assess validity in clinical settings, including acute care, long term care and assisted living care facilities. Our long term goals include non-intrusive approaches to assess balance competence during ADL in independent living environments.

  10. Palliation in pancreatic cancer.

    PubMed

    Kruse, E James

    2010-04-01

    Pancreatic cancer is rarely curable, and because of its location causes significant symptoms for patients in need of palliation. The common problems of incurable pancreatic cancer are biliary obstruction, duodenal obstruction, and pain. Approaches include surgical, endoscopic and radiologic interventions. This article discusses the palliative options and controversies related to these symptoms.

  11. 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

  12. Maldigestion from pancreatic exocrine insufficiency.

    PubMed

    Pongprasobchai, Supot

    2013-12-01

    Pancreatic exocrine insufficiency (PEI) is one of the long-term consequences of chronic pancreatitis (CP). Majority of patients with PEI were undiagnosed or undertreated. Inadequately treated or subclinical severe PEI causes malnutrition and may pose the patients at risk of premature atherosclerosis and cardiovascular events. Indication of pancreatic enzyme replacement therapy (PERT) is patients with severe PEI, as indicated by the presence of steatorrhea, diarrhea, weight loss, fecal fat > 7 g/day, (13) C-mixed triglyceride breath test < 29%, fecal elastase < 100 ug/g stool, imaging or endoscopic findings of pancreatic ductal dilatation or calculi, and eight endosonographic criteria of CP. The mainstay treatment of PEI is PERT. Dietary fat restriction is unnecessary. PERT with lipase > 40,000 U per meal is recommended. Enteric-coating may be preferred to conventional enzymes because of the availability of high-dose preparations and no need of acid suppression co-therapy. Administration of enzymes with meals is proven to be the most effective regimen. Response to PERT should be measured by the improvement of patients' symptoms, nutritional status, and, in selected cases, by fecal fat or (13) C-mixed triglyceride breath test. Patients unresponsive to PERT should be checked for compliance, increase the dose of lipase to 90,000 units/meal or co-therapy with proton pump inhibitor. In patient with previous gastrointestinal surgery that may interfere enzyme-food mixing, opening the capsules and administering the enzyme granules with meals. Finally, search for small intestinal bacterial overgrowth syndrome and other causes of small bowel malabsorption. PMID:24251713

  13. 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.

  14. 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

  15. Natural course of acute pancreatitis.

    PubMed

    Beger, H G; Rau, B; Mayer, J; Pralle, U

    1997-02-01

    Acute pancreatitis comprises, in terms of clinical, pathologic, biochemical, and bacteriologic data, four entities. Interstitial edematous pancreatitis and necrotizing pancreatitis are the most frequent clinical manifestations; pancreatic pseudocyst and pancreatic abscess are late complications after necrotizing pancreatitis, developing after 3 to 5 weeks. Determinants of the natural course of acute pancreatitis are pancreatic parenchymal necrosis, extrapancreatic retroperitoneal fatty tissue necrosis, biologically active compounds in pancreatic ascites, and infection of necrosis. Early in the course of acute pancreatitis multiple organ failure is the consequence of various inflammatory mediators that are released from the inflammatory process and from activated leukocytes attracted by pancreatic injury. During the late course, starting the second week, local and systemic septic complications are dominant. Around 80% of deaths in acute pancreatitis are caused by septic complications. The infection of pancreatic necrosis occurs in 8% to 12% of acute pancreatitis and in 30% to 40% of patients with necrotizing pancreatitis. Bacteriologic analysis of intraoperative smears and aspirates reveals predominantly gram-negative germs deriving from the intestine, most frequently Escherichia coli. It has been confirmed that after necrotizing pancreatitis a considerable large group of patients suffer long-lasting exocrine and endocrine insufficiency.

  16. 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

  17. A binuclear complex constituted by diethyldithiocarbamate and copper(I) functions as a proteasome activity inhibitor in pancreatic cancer cultures and xenografts.

    PubMed

    Han, Jinbin; Liu, Luming; 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.

  18. Infectious pancreatic necrosis: its detection and identification

    USGS Publications Warehouse

    Wolf, K.

    1965-01-01

    Ultimate control of infectious pancreatic necrosis (IPN) in hatcheries depends largely upon learning where the virus occurs. To detect the presence of virus either susceptible fish or susceptible fish cell cultures may be used as test systems. In modern virology, it is generally agreed that cell cultures are more convenient, are usually a much more sensitive test system, and allow more rapid determinations.

  19. Clinical nutrition in pancreatitis.

    PubMed

    McClave, S A; Snider, H; Owens, N; Sexton, L K

    1997-10-01

    In patients with acute pancreatitis or an acute flare of chronic pancreatitis, a discrepancy exists between increased protein/calorie requirements induced by a hypermetabolic stress state and reduced ingestion/assimilation of exogenous nutrients, which promotes progressive nutritional deterioration. Patients with severe pancreatitis (defined by > or =3 Ranson criteria, an APACHE II score of > or =10, development of major organ failure, and/or presence of pancreatic necrosis) are more likely to require aggressive nutritional support than patients with mild disease. The type of formula and level of the gastrointestinal tract into which nutrients are infused determine the degree to which pancreatic exocrine secretion is stimulated. Animal studies and early prospective randomized controlled trials in humans suggest that total enteral nutrition via jejunal feeding may be the preferred route to parenteral alimentation in this disease setting.

  20. The influence of chronic intake of saccharin on rat hepatic and pancreatic function and morphology: gender differences.

    PubMed

    Andrejić, Bojana M; Mijatović, Vesna M; Samojlik, Isidora N; Horvat, Olga J; Ćalasan, Jelena D; Đolai, Matilda A

    2013-05-01

    There are opposite hypotheses on the effect of saccharin. Our aim was reviewing the influence of chronically ingested saccharin on the function and histological structure of liver and pancreas and all this in light of gender differences. The rats were divided into control group - (Group C) and saccharin-treated group - (Group S) which was given a normal diet and 0.0005% saccharin in drinking water for 6 weeks. Liver and pancreas were histologically processed and quantitative histological analysis was performed. Glucose blood levels and plasma activities of aspartate transaminase (AST) and alanine transaminase (ALT), body weight, and food intake were analyzed. Quantitative histological analysis determined that the values of diameter and volume density of both Langerhans islets and exocrine acini were significantly higher in S group, especially in males. AST levels were significantly higher in treated group. Glucose levels were higher in treated group, mainly due to the values of the female subgroup. Food intake was significantly higher in control group, while weight gain was higher in treated group. Treated males had significantly higher food intake and weight gain in comparison with treated females. The data presented here suggests that chronic saccharin intake affects the examined parameters. Reported facts reflect various metabolic, hormonal and neural responses in males and females.

  1. 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

  2. Endoscopic pancreatic and biliary manometry in pancreatic, biliary, and papillary disease, and after endoscopic sphincterotomy and surgical sphincteroplasty.

    PubMed Central

    Gregg, J A; Carr-Locke, D L

    1984-01-01

    Endoscopic manometry was used to measure pancreatic duct, common bile duct, pancreatic duct sphincter and bile duct sphincter pressures in 43 healthy volunteers and 162 patients with a variety of papillary, pancreatic and biliary disorders. Common bile duct pressure was significantly raised after cholecystectomy, with common bile duct stones and papillary stenosis but pancreatic duct pressure only in papillary stenosis. After endoscopic sphincterotomy mean common bile duct pressure fell from 11.2 to 1.1 mmHg and pancreatic duct pressure from 18.0 to 11.2 mmHg. Distinct pancreatic duct sphincter and bile duct sphincter zones were identified as phasic pressures of 3-12 waves/minute on pull-through from pancreatic duct and common bile duct to duodenum. Pancreatic duct sphincter pressures were higher with common bile duct stones and stenosis whereas bile duct sphincter pressures were higher in pancreatitis and stenosis. Bile duct sphincter activity was present in 60% of patients after surgical sphincteroplasty but 21% of patients after endoscopic sphincterotomy. Endoscopic manometry facilitated the diagnosis of papillary stenosis, has allowed study of papillary pathophysiology and has shown a functional inter-relationship between the two sphincteric zones. PMID:6500363

  3. Test-specific control conditions for functional analyses.

    PubMed

    Fahmie, Tara A; Iwata, Brian A; Querim, Angie C; Harper, Jill M

    2013-01-01

    Most functional analyses of problem behavior include a common condition (play or noncontingent reinforcement) as a control for both positive and negative reinforcement. However, test-specific conditions that control for each potential source of reinforcement may be beneficial occasionally. We compared responding during alone, ignore, play, and differential reinforcement of other behavior (DRO) control conditions for individuals whose problem behavior was maintained by positive or negative reinforcement. Results showed that all of the conditions were effective controls for problem behavior maintained by positive reinforcement; however, the DRO condition was consistently ineffective as a control for problem behavior maintained by negative reinforcement. Implications for the design of functional analyses and future research are discussed.

  4. Acute Obstructive Suppurative Pancreatic Ductitis

    PubMed Central

    Palakodeti, Sandeep; Munroe, Craig

    2016-01-01

    Acute obstructive suppurative pancreatic ductitis (AOSPD) is a rare clinical entity defined as suppuration from the pancreatic duct without concomitant pancreatic cyst, abscess, or necrosis. We describe a case of AOSPD in a woman with a past medical history of type 2 diabetes and chronic pancreatitis who presented with abdominal sepsis, which resolved only after therapeutic endoscopic retrograde cholangiopancreatography. Our case highlights the importance of considering AOSPD as a cause of abdominal sepsis particularly in patients with chronic pancreatitis or any recent pancreatic duct instrumentation and demonstrates that treatment requires prompt drainage and decompression of the pancreatic duct.

  5. Executive Function in Preschool Children: Test-Retest Reliability

    PubMed Central

    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 preschool period using Conflict and Delay subtests that had a cool (abstract) or hot (extrinsic reward) focus. Results from 151 children in three age groups (2.5, 3.5, and 4.5) suggested acceptable same-day test-retest reliability on all but Delay-Cool subtasks. These findings will inform appropriate measurement selection and development for future studies. PMID:21643523

  6. Conservative management of pediatric pancreatic pseudocyst using octreotide acetate.

    PubMed

    Mulligan, C; Howell, C; Hatley, R; Martindale, R; Clark, J

    1995-03-01

    Pancreatic pseudocysts in children are rare. A total of 213 cases have been reported in the literature, the majority secondary to trauma (65%). Treatment options range from conservative, non-operative management to operative drainage. Octreotide acetate, a long-acting analog of somatostatin, is a synthetic peptide with a variety of endocrine and gastrointestinal functions. Octreotide has been successfully used following pancreatic surgery to reduce exocrine function and most recently in the management of adult pancreatic pseudocysts. We report the efficacy of octreotide, as an adjunct to treatment, in two children with pancreatic pseudocyst. Each child was treated conservatively with bowel rest, hyperalimentation, and octreotide acetate (2.5 micrograms/kg SQ QD). Complete resolution of the pseudocysts occurred within 5 weeks. We conclude that octreotide acetate is a safe and potentially effective adjunct in the treatment of pediatric pancreatic pseudocyst, and should be added to the management of pseudocyst before drainage procedures.

  7. Protein restriction in early life is associated with changes in insulin sensitivity and pancreatic β-cell function during pregnancy.

    PubMed

    Ignácio-Souza, Letícia Martins; Reis, Sílvia Regina; Arantes, Vanessa Cristina; Botosso, Bárbara Laet; Veloso, Roberto Vilela; Ferreira, Fabiano; Boschero, Antonio Carlos; Carneiro, Everardo Magalhães; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2013-01-28

    Malnutrition in early life impairs glucose-stimulated insulin secretion in adulthood. Conversely, pregnancy is associated with a significant increase in glucose-stimulated insulin secretion under conditions of normoglycaemia. A failure in β-cell adaptive changes may contribute to the onset of diabetes. Thus, glucose homeostasis and β-cell function were evaluated in control-fed pregnant (CP) and non-pregnant (CNP) or protein-restricted pregnant (LPP) and non-pregnant (LPNP) rats, from fetal to adult life, and in protein-restricted rats that were recovered after weaning (RP and RNP). The typical insulin resistance of pregnancy was not observed in the RP rats, nor did pregnancy increase the insulin content/islet in the LPP group. The glucose dose-response curves from pregnant rats were shifted to the left in relation to the non-pregnant rats, except in the recovered group. Glucose utilisation but not oxidation in islets from the RP and LPP groups was reduced at a concentration of 8.3 mm-glucose compared with islets from the CP group. Cyclic AMP content and the potentiation of glucose-stimulated insulin secretion by isobutylmethylxanthine at a concentration of 2.8 mm-glucose indicated increased adenylyl cyclase 3 activity but reduced protein kinase A-α activity in islets from the RP and LPP rats. Protein kinase C (PKC)-α but not phospholipase C (PLC)-β1 expression was reduced in islets from the RP group. Phorbol-12-myristate 13-acetate produced a less potent stimulation of glucose-stimulated insulin secretion in the RP group. Thus, the alterations exhibited by islets from the LPP group appeared to be due to reduced islet mass and/or insulin biosynthesis. In the RP group the loss of the adaptive capacity apparently resulted from uncoupling between glucose metabolism and the amplifying signals of the secretory process, as well as a severe attenuation of the PLC/PKC pathway. PMID:22475371

  8. 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

  9. Protein restriction in early life is associated with changes in insulin sensitivity and pancreatic β-cell function during pregnancy.

    PubMed

    Ignácio-Souza, Letícia Martins; Reis, Sílvia Regina; Arantes, Vanessa Cristina; Botosso, Bárbara Laet; Veloso, Roberto Vilela; Ferreira, Fabiano; Boschero, Antonio Carlos; Carneiro, Everardo Magalhães; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2013-01-28

    Malnutrition in early life impairs glucose-stimulated insulin secretion in adulthood. Conversely, pregnancy is associated with a significant increase in glucose-stimulated insulin secretion under conditions of normoglycaemia. A failure in β-cell adaptive changes may contribute to the onset of diabetes. Thus, glucose homeostasis and β-cell function were evaluated in control-fed pregnant (CP) and non-pregnant (CNP) or protein-restricted pregnant (LPP) and non-pregnant (LPNP) rats, from fetal to adult life, and in protein-restricted rats that were recovered after weaning (RP and RNP). The typical insulin resistance of pregnancy was not observed in the RP rats, nor did pregnancy increase the insulin content/islet in the LPP group. The glucose dose-response curves from pregnant rats were shifted to the left in relation to the non-pregnant rats, except in the recovered group. Glucose utilisation but not oxidation in islets from the RP and LPP groups was reduced at a concentration of 8.3 mm-glucose compared with islets from the CP group. Cyclic AMP content and the potentiation of glucose-stimulated insulin secretion by isobutylmethylxanthine at a concentration of 2.8 mm-glucose indicated increased adenylyl cyclase 3 activity but reduced protein kinase A-α activity in islets from the RP and LPP rats. Protein kinase C (PKC)-α but not phospholipase C (PLC)-β1 expression was reduced in islets from the RP group. Phorbol-12-myristate 13-acetate produced a less potent stimulation of glucose-stimulated insulin secretion in the RP group. Thus, the alterations exhibited by islets from the LPP group appeared to be due to reduced islet mass and/or insulin biosynthesis. In the RP group the loss of the adaptive capacity apparently resulted from uncoupling between glucose metabolism and the amplifying signals of the secretory process, as well as a severe attenuation of the PLC/PKC pathway.

  10. 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

  11. 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

  12. 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

  13. [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

  14. 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.

  15. An expert system for synoptic interpretation of lung function tests.

    PubMed

    Heise, D; Kroker, P; Mailänder, A

    1990-01-01

    We simulate the interpretation process by the testing of preformed working hypotheses. A clinical syndrome, "bronchial obstruction," is described by a set of suitable parameters (FEV1, MMEF, Raw, etc.). For a given patient, this set forms a normalized vector. It has to be compared with equivalent data derived from patients which fulfilled the criteria for the clinical syndrome in question. If the patient's vector has a similar direction as the vector of the collective, the working hypothesis is accepted. The length of the vector is then used to quantify the severity of the functional disturbances in verbal terms ("slight," "moderate," "severe"). The limits used for severity grading and the typical parameter pattern for the given syndrome are adapted to the user's criteria by a built-in learning capability. On the other hand, the assembled data may be used for the training of newcomers. The use of vector algorithms allows for a high flexibility of our program with respect to all methods used in lung function testing. PMID:2117121

  16. An expert system for synoptic interpretation of lung function tests.

    PubMed

    Heise, D; Kroker, P; Mailänder, A

    1990-01-01

    We simulate the interpretation process by the testing of preformed working hypotheses. A clinical syndrome, "bronchial obstruction," is described by a set of suitable parameters (FEV1, MMEF, Raw, etc.). For a given patient, this set forms a normalized vector. It has to be compared with equivalent data derived from patients which fulfilled the criteria for the clinical syndrome in question. If the patient's vector has a similar direction as the vector of the collective, the working hypothesis is accepted. The length of the vector is then used to quantify the severity of the functional disturbances in verbal terms ("slight," "moderate," "severe"). The limits used for severity grading and the typical parameter pattern for the given syndrome are adapted to the user's criteria by a built-in learning capability. On the other hand, the assembled data may be used for the training of newcomers. The use of vector algorithms allows for a high flexibility of our program with respect to all methods used in lung function testing.

  17. 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

  18. 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

  19. Spatial weighting functions: transient hydraulic tests and heterogeneous media.

    PubMed

    Molz, Fred J; Guan, Jianyong; Wang, Jinjun

    2005-01-01

    To improve understanding of property measurements in heterogeneous media, an energy-based weighting function concept is developed. In (assumed) homogeneous media, the instrument spatial weighting function (ISWF) depends only on the energy dissipation distribution set up by the measurement procedure and it reduces to simply inverse sample volume (uniform weighting) for 1-D parallel flow case (ideal permeameter). For 1-D transient flow in homogeneous media, such as with slug tests, the ISWF varies with position and time, with 95% of the total weighting contained within 115 well radii, even late in the test. In the heterogeneous case, the determination of the ISWF is connected to the problem of determining an equivalent hydraulic conductivity (K), where the criterion for equivalence is based on equal energy dissipation rate rather than equal volume discharge. The discharge-based equivalent K (K(E)) and the energy-based equivalent K in heterogeneous media (K(eh)) are not equal in general, with K(eh) typically above the nodal arithmetic mean K. The possibly more fundamental problem is that as one makes K measurements in heterogeneous media at different locations or on different cores of heterogeneous materials, the ISWF will be heterogeneity dependent, implying that the averaging process resulting in the equivalent K value also varies with position. If the testing procedure is transient, then the averaging process varies with time. This suggests a fundamental ambiguity in the interpretation of hydraulic conductivity measurements in heterogeneous media that may impact how we approach modeling and prediction in a practical sense (Molz 2003). Further research is suggested.

  20. Testing galaxy formation models with galaxy stellar mass functions

    NASA Astrophysics Data System (ADS)

    Lim, S. H.; Mo, H. J.; Lan, Ting-Wen; Ménard, Brice

    2016-10-01

    We compare predictions of a number of empirical models and numerical simulations of galaxy formation to the conditional stellar mass functions (CSMF) of galaxies in groups of different masses obtained recently by Lan et al. to test how well different models accommodate the data. The observational data clearly prefer a model in which star formation in low-mass halos changes behavior at a characteristic redshift zc ˜ 2. There is also tentative evidence that this characteristic redshift depends on environment, becoming zc ˜ 4 in regions that eventually evolve into rich clusters of galaxies. The constrained model is used to understand how galaxies form and evolve in dark matter halos, and to make predictions for other statistical properties of the galaxy population, such as the stellar mass functions of galaxies at high z, the star formation and stellar mass assembly histories in dark matter halos. A comparison of our model predictions with those of other empirical models shows that different models can make vastly different predictions, even though all of them are tuned to match the observed stellar mass functions of galaxies.

  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.

  2. Evaluation of pulmonary function tests by using fuzzy logic theory.

    PubMed

    Uncü, Umit

    2010-06-01

    Pulmonary Function Tests (PFTs) are very important in the medical evaluation of patients suffering from "shortness of breath", and they are effectively used for the diagnosis of pulmonary diseases, such as COPD (i.e. chronic obstructive pulmonary diseases). Measurement of Forced Vital Capacity (FVC) and Forced Expiratory Flow in the 1st second (FEV1) are very important for controlling the treatment of COPD. During PFTs, some difficulties are encountered which complicate the comparison of produced graphs with the standards. These mainly include the reluctance of the patients to co-operate and the physicians' weaknesses to make healthy interpretations. Main tools of the diagnostic process are the symptoms, laboratory tests or measurements and the medical history of the patient. However, quite frequently, most of the medical information obtained from the patient is uncertain, exaggerated or ignored, incomplete or inconsistent. Fuzziness encountered during PFT is very important. In this study, the purpose is to use "fuzzy logic" approach to facilitate reliable and fast interpretation of PFT graphical outputs. A comparison is made between this approach and methodologies adopted in previous studies. Mathematical models and their coefficients for the spirometric plots are introduced as fuzzy numbers. Firstly, a set of rules for categorizing coefficients of mathematical models obtained. Then, a fuzzy rule-base for a medical inference engine is constructed and a diagnostic "expert system COPDes" designed. This program, COPDes helps for diagnosing the degree of COPD for the patient under test.

  3. 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

  4. Diagnosis of autoimmune pancreatitis

    PubMed Central

    Matsubayashi, Hiroyuki; Kakushima, Naomi; Takizawa, Kohei; Tanaka, Masaki; Imai, Kenichiro; Hotta, Kinichi; Ono, Hiroyuki

    2014-01-01

    Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis that is increasingly being reported. The presentation and clinical image findings of AIP sometimes resemble those of several pancreatic malignancies, but the therapeutic strategy differs appreciably. Therefore, accurate diagnosis is necessary for cases of AIP. To date, AIP is classified into two distinct subtypes from the viewpoints of etiology, serum markers, histology, other organ involvements, and frequency of relapse: type 1 is related to IgG4 (lymphoplasmacytic sclerosing pancreatitis) and type 2 is related to a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis). Both types of AIP are characterized by focal or diffuse pancreatic enlargement accompanied with a narrowing of the main pancreatic duct, and both show dramatic responses to corticosteroid. Unlike type 2, type 1 is characteristically associated with increasing levels of serum IgG4 and positive serum autoantibodies, abundant infiltration of IgG4-positive plasmacytes, frequent extrapancreatic lesions, and relapse. These findings have led several countries to propose diagnostic criteria for AIP, which consist of essentially similar diagnostic items; however, several differences exist for each country, mainly due to differences in the definition of AIP and the modalities used to diagnose this disease. An attempt to unite the diagnostic criteria worldwide was made with the publication in 2011 of the international consensus diagnostic criteria for AIP, established at the 2010 Congress of the International Association of Pancreatology (IAP). PMID:25469024

  5. 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

  6. Autoimmune pancreatitis and cholangitis

    PubMed Central

    Jani, Niraj; Buxbaum, James

    2015-01-01

    Autoimmune pancreatitis (AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4 (IgG4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra-pancreatic manifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings. PMID:26558153

  7. Fatal Pancreatic Panniculitis Associated with Acute Pancreatitis: A Case Report

    PubMed Central

    Lee, Woo Sun; Kim, Mi Yeon; Kim, Sang Woo; Paik, Chang Nyol; Kim, Hyung Ok

    2007-01-01

    Pancreatic panniculitis is a rare disease in which necrosis of fat in the panniculus and other distant foci occurs in the setting of pancreatic diseases; these diseases include acute and chronic pancreatitis, pancreatic carcinoma, pseudocyst, and other pancreatic diseases. This malady is manifested as tender erythematous nodules on the legs, buttock, or trunk. Histopathologically, it shows the pathognomonic findings of focal subcutaneous fat necrosis and ghost-like anucleated cells with a thick shadowy wall. We herein report a case of fatal pancreatic panniculitis that was associated with acute pancreatitis in a 50-yr-old man. He presented with a 3-week history of multiple tender skin nodules, abdominal pain and distension. Laboratory and radiologic findings revealed acute pancreatitis, and skin biopsy showed pancreatic panniculitis. Despite intensive medical care, he died of multi-organ failure 3 weeks after presentation. PMID:17982246

  8. Familial pancreatic cancer.

    PubMed

    Klein, A P; Hruban, R H; Brune, K A; Petersen, G M; Goggins, M

    2001-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States and will be responsible for an estimated 28,900 deaths in 2001. Relatively little is known of its etiology, and the only well-established risk factor is cigarette smoking. Studies over the past 3 decades have shown that 4%-16% of patients with pancreatic cancer have a family history of the disease. A small fraction of this aggregation can be accounted for in inherited cancer syndromes, including familial atypical multiple-mole melanoma, Peutz-Jeghers syndrome, hereditary breast-ovarian cancer, hereditary pancreatitis, and hereditary nonpolyposis colorectal cancer. These syndromes arise as a result of germline mutations in the BRCA2, pl6 (familial atypical multiple-mole melanoma), mismatch repair (hereditary nonpolyposis colorectal cancer), and STK11 (Peutz-Jeghers syndrome) genes. In addition, hereditary plays a role in predisposing certain patients with apparently sporadic pancreatic cancer. Many patients with pancreatic cancers caused by a germline mutation in a cancer-causing gene do not have a pedigree that is suggestive of a familial cancer syndrome. A recent prospective analysis of the pedigrees in the National Familial Pancreatic Tumor Registry found that individuals with a family history of pancreatic cancer in multiple first-degree relatives have a high risk of pancreatic cancer themselves. The identification of such high-risk individuals will help clinicians target screening programs and develop preventive interventions with the hope of reducing the mortality of pancreatic cancer in these families.

  9. 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 ...

  10. [Primary pancreatic plasmacytoma].

    PubMed

    Sánchez Acevedo, Z; Pomares Rey, B; Alpera Tenza, M R; Andrada Becerra, E

    2014-01-01

    Extramedullary plasmacytomas are uncommon malignant plasma cell tumors that present outside the bone marrow; 80% of extramedullary plasmacytomas are located in the upper respiratory tract, and gastrointestinal plasmacytomas are rare. We present the case of an asymptomatic 65-year-old man in whom a pancreatic mass was found incidentally. The lesion was determined to be a pancreatic plasmacytoma after fine-needle aspiration cytology and surgical resection. No clinical, laboratory, or imaging findings indicative of multiple myeloma or association with other plasmacytomas were found, so the tumor was considered to be a primary pancreatic plasmacytoma. PMID:22738942

  11. Acetylcholine and muscarinic receptor function in cerebral cortex of diabetic young and old male Wistar rats and the role of muscarinic receptors in calcium release from pancreatic islets.

    PubMed

    Savitha, Balakrishnan; Joseph, Binoy; Peeyush Kumar, T; Paulose, C S

    2010-04-01

    We investigated acetylcholine esterase (AChE) activity, acetylcholine and muscarinic M1, M3 receptors kinetics in the cerebral cortex of young and old streptozotocin induced and insulin treated diabetic rats. The role of muscarinic receptors in intracellular calcium release from pancreatic islets was studied in vitro. Wistar rats of 7 and 90-weeks old were used. All studies were done in cerebral cortex. AChE assay was done by spectrophotometric method. Radioreceptor binding assays were done for Acetylcholine, Muscarinic M1 and M3 receptors using specific ligands. Calcium imaging was done using fluo4-AM in pancreatic cells. Ninety-weeks old control rats showed significantly decreased Vmax and increased Km for AChE compared to 7-weeks old control rats. An increased Vmax observed in both 7 and 90-weeks old diabetic groups with significant decrease in Km. Scatchard analysis using specific agonists showed significant decrease in the B (max) and K (d) of acetylcholine and muscarinic M1 receptors in 90-weeks old control rats compared to 7-weeks old control. Binding studies for M3 receptors showed no significant change compared to 7-weeks old control. Acetylcholine, muscarinic M1 and M3 receptor number significantly increased in 90-weeks old diabetic rat groups compared to their respective controls. Insulin treatment significantly reversed the binding parameters to near control compared to diabetic group. In vitro studies showed that acetylcholine through muscarinic M1 and M3 receptors' stimulated calcium release from the pancreatic islets. Thus our studies suggest that Insulin signaling play an important part in differentially regulating pancreatic cholinergic activity, and the diabetes mediated cortical dysfunctions with age.

  12. Role of trypsin/creatinine clearance ratio in the differential diagnosis of chronic pancreatic disease.

    PubMed

    Farini, R; Fabris, C; del Favero, G; Bonvicini, P; de' Best, T; Piccoli, A; Baccaglini, U; Plebani, M; Pedrazzoli, S; Kind, R; Ceriotti, G; Naccarato, R

    1981-08-01

    Trypsin/creatinine clearance ratio--a recently proposed screening test for pancreatic cancer--was assessed in 45 subjects (17 control subjects, 15 patients with pancreatic cancer, and 13 with chronic pancreatitis). A statistically significant increase of the ratio was detected not only in pancreatic cancer, but also in chronic calcifying pancreatitis. Thus, the previously reported clinical usefulness of the test in pancreatic cancer diagnosis was not substantiated by the present data. Although not fully investigated as yet, reasons for an abnormal ratio are probably independent of the neoplastic or inflammatory nature of the pancreatic disease. Science renal enzyme excretion (alpha-glucosidase, gamma-glutamyltranspeptidase, leucine aminopeptidase) was not found to be invariably elevated when trypsin/creatinine clearance ratio was increased, tubular damage cannot be assumed as constituting the only reason for an altered clearance ratio.

  13. Type 1 Autoimmune Pancreatitis Can Transform into Chronic Pancreatitis: A Long-Term Follow-Up Study of 73 Japanese Patients

    PubMed Central

    Maruyama, Masahiro; Arakura, Norikazu; Ozaki, Yayoi; Watanabe, Takayuki; Ito, Tetsuya; Yoneda, Suguru; Maruyama, Masafumi; Muraki, Takashi; Hamano, Hideaki; Matsumoto, Akihiro; Kawa, Shigeyuki

    2013-01-01

    Some patients with autoimmune pancreatitis (AIP) form pancreatic stones suggestive of transformation into chronic pancreatitis (CP). The present study examined the underlying risk factors and mechanism of AIP progression to confirmed CP. We compared the clinical and laboratory parameters of subjects who progressed to confirmed CP with those of the subjucts who did not in a cohort of 73 type 1 AIP patients. A total of 16 (22%) AIP patients progressed to CP. Univariate analysis revealed that relapse was significantly more frequent in the progression group, and multivariate analysis indicated that pancreatic head swelling (OR 12.7, P = 0.023) and nonnarrowing of the main pancreatic duct in the pancreatic body (OR 12.6, P = 0.001) were significant independent risk factors for progression to CP. Kaplan-Meier testing showed that the progression rate to CP was approximately 10% at 3 years and 30% at 10 years in total AIP patients and 30% at 3 years and 60% at 10 years in subjects with both risk factors. AIP with pancreatic head swelling and a history of relapse may cause pancreatic juice stagnation and nonnarrowing of the main pancreatic duct in the pancreatic body, which can progress to advanced stage chronic pancreatitis. PMID:23762066

  14. 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

  15. 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.

  16. [Chronic pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group].

    PubMed

    Takács, Tamás; Czakó, László; Dubravcsik, Zsolt; Farkas, Gyula; Hegyi, Péter; Hritz, István; Kelemen, Dezső; Lásztity, Natália; Morvay, Zita; Oláh, Attila; Pap, Ákos; Párniczky, Andrea; Patai, Árpád; Sahin-Tóth, Miklós; Szentkereszti, Zsolt; Szmola, Richárd; Tiszlavicz, László; Szücs, Ákos

    2015-02-15

    Chronic pancreatitis is an inflammatory disease associated with structural and functional damage of the pancreas. In most cases pain, maldigestion and weight loss are the leading symptoms, which significantly worsen the quality of life. Correct diagnosis and differential diagnosis of chronic pancreatitis and treatment of these patients requires up-to-date and evidence based treatment guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available international guidelines and evidence. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and complemented and/or modified the international guidelines if it was necessary. 123 relevant clinical questions in 11 topics were defined. Evidence was classified according to the UpToDate® grading system. The draft of the guidelines were presented and discussed at the consensus meeting in September 12, 2014. All clinical questions were accepted with total or strong agreement. The present guideline is the first evidence based guideline for chronic pancreatitis in Hungary. This guideline provides very important and helpful data for tuition, everyday practice and proper financing of chronic pancreatitis. Therefore, the authors believe that these guidelines will widely become a basic reference in Hungary.

  17. A comparison of visual function tests in eyes with maculopathy.

    PubMed

    Fish, G E; Birch, D G; Fuller, D G; Straach, R

    1986-09-01

    Several recently developed tests of visual function, including the Potential Acuity Meter (PAM), laser interferometer (LI), white-light interferometer (WLI), blue field entoptic phenomenon, and focal electroretinogram (ERG) were compared in 81 eyes with clear media and known macular disease. The results indicate that the PAM, the LI, and the WLI overread relative to Snellen acuity. Laser interferometric acuity values differed from Snellen acuity by at least 1.5 octaves in approximately 40% of all eyes, regardless of stimulus size (2, 5, or 8 degrees). Similar results were obtained with the WLI. Agreement with Snellen acuity was better for the PAM, with 91% of eyes falling within 1.5 octaves of Snellen acuity. Blue field and focal ERG results were categorized as normal or abnormal. While not producing Snellen equivalents, abnormal results from the blue field and focal ERG corresponded with poor Snellen acuity (less than 20/40) in 65% and 91% of eyes, respectively. Assuming that media opacities do not prevent adequate retinal stimulation, the present results suggest that the PAM and focal ERG are the most reliable for evaluating macular function when maculopathy is present.

  18. 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…

  19. 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.

  20. Exenatide does not evoke pancreatitis and attenuates chemically induced pancreatitis in normal and diabetic rodents

    PubMed Central

    Smith, Pamela A.; Sablan, Emmanuel J.; Polizzi, Clara J.; Aumann, Donald E.; Villescaz, Christiane; Hargrove, Diane M.; Gedulin, Bronislava R.; Lu, Melissa G. W.; Adams, Lisa; Whisenant, Tina; Roy, Denis; Parkes, David G.

    2010-01-01

    The risk of developing pancreatitis is elevated in type 2 diabetes and obesity. Cases of pancreatitis have been reported in type 2 diabetes patients treated with GLP-1 (GLP-1R) receptor agonists. To examine whether the GLP-1R agonist exenatide potentially induces or modulates pancreatitis, the effect of exenatide was evaluated in normal or diabetic rodents. Normal and diabetic rats received a single exenatide dose (0.072, 0.24, and 0.72 nmol/kg) or vehicle. Diabetic ob/ob or HF-STZ mice were infused with exenatide (1.2 and 7.2 nmol·kg−1·day−1) or vehicle for 4 wk. Post-exenatide treatment, pancreatitis was induced with caerulein (CRN) or sodium taurocholate (ST), and changes in plasma amylase and lipase were measured. In ob/ob mice, plasma cytokines (IL-1β, IL-2, IL-6, MCP-1, IFNγ, and TNFα) and pancreatitis-associated genes were assessed. Pancreata were weighed and examined histologically. Exenatide treatment alone did not modify plasma amylase or lipase in any models tested. Exenatide attenuated CRN-induced release of amylase and lipase in normal rats and ob/ob mice but did not modify the response to ST infusion. Plasma cytokines and pancreatic weight were unaffected by exenatide. Exenatide upregulated Reg3b but not Il6, Ccl2, Nfkb1, or Vamp8 expression. Histological analysis revealed that the highest doses of exenatide decreased CRN- or ST-induced acute inflammation, vacuolation, and acinar single cell necrosis in mice and rats, respectively. Ductal cell proliferation rates were low and similar across all groups of ob/ob mice. In conclusion, exenatide did not modify plasma amylase and lipase concentrations in rodents without pancreatitis and improved chemically induced pancreatitis in normal and diabetic rodents. PMID:20923958

  1. 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

  2. Multiloop Integral System Test (MIST): MIST Facility Functional Specification

    SciTech Connect

    Habib, T F; Koksal, C G; Moskal, T E; Rush, G C; Gloudemans, J R

    1991-04-01

    The Multiloop Integral System Test (MIST) is part of a multiphase program started in 1983 to address small-break loss-of-coolant accidents (SBLOCAs) specific to Babcock and Wilcox designed plants. MIST is sponsored by the US Nuclear Regulatory Commission, the Babcock Wilcox Owners Group, the Electric Power Research Institute, and Babcock and Wilcox. The unique features of the Babcock and Wilcox design, specifically the hot leg U-bends and steam generators, prevented the use of existing integral system data or existing integral facilities to address the thermal-hydraulic SBLOCA questions. MIST was specifically designed and constructed for this program, and an existing facility -- the Once Through Integral System (OTIS) -- was also used. Data from MIST and OTIS are used to benchmark the adequacy of system codes, such as RELAP5 and TRAC, for predicting abnormal plant transients. The MIST Functional Specification documents as-built design features, dimensions, instrumentation, and test approach. It also presents the scaling basis for the facility and serves to define the scope of work for the facility design and construction. 13 refs., 112 figs., 38 tabs.

  3. Cosmological tests with the FSRQ gamma-ray luminosity function

    NASA Astrophysics Data System (ADS)

    Zeng, Houdun; Melia, Fulvio; Zhang, Li

    2016-11-01

    The extensive catalogue of gamma-ray selected flat-spectrum radio quasars (FSRQs) produced by Fermi during a four-year survey has generated considerable interest in determining their gamma-ray luminosity function (GLF) and its evolution with cosmic time. In this paper, we introduce the novel idea of using this extensive database to test the differential volume expansion rate predicted by two specific models, the concordance Λ cold dark matter (ΛCDM) and Rh = ct cosmologies. For this purpose, we use two well-studied formulations of the GLF, one based on pure luminosity evolution (PLE) and the other on a luminosity-dependent density evolution (LDDE). Using a Kolmogorov-Smirnov test on one-parameter cumulative distributions (in luminosity, redshift, photon index and source count), we confirm the results of earlier works showing that these data somewhat favour LDDE over PLE; we show that this is the case for both ΛCDM and Rh = ct. Regardless of which GLF one chooses, however, we also show that model selection tools very strongly favour Rh = ct over ΛCDM. We suggest that such population studies, though featuring a strong evolution in redshift, may none the less be used as a valuable independent check of other model comparisons based solely on geometric considerations.

  4. Deep Bed Adsorption Testing using Silver-Functionalized Aerogel

    SciTech Connect

    Nick Soelberg; Tony Watson

    2012-06-01

    Nuclear fission results in the production of fission products and activation products, some of which tend to be volatile during used fuel reprocessing and evolve in gaseous species into the reprocessing facility off-gas systems. Analyses have shown that I129, due to its radioactivity, high potential mobility in the environment, and high longevity (half life of 15.7 million years), can require control efficiencies of up to 1,000x or higher to meet regulatory emission limits. Two Aerogel sorption tests that have been performed this fiscal year. The maximum iodine decontamination factor (DF) was measured to be over 10,000, above the 1,000-10,000 target DF range. The mass transfer zone may be as short as 0.5 inches under the sorption conditions of the first test. Only a small fraction of the iodine sorbed on Bed 1 was desorbed during the purge periods. The silver-functionalized Aerogel appears to have potential to be a very effective and efficient iodine sorbent.

  5. 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 ...

  6. 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 ...

  7. 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, ...

  8. Nutrition support in pancreatitis.

    PubMed

    Marulendra, S; Kirby, D F

    1995-04-01

    Nutrition support in patients with pancreatitis has created a challenge for clinicians. Because the pancreas is normally stimulated by the ingestion of food, particularly fat, patients are often denied oral nutrition. This reduction in the ingestion of food, together with the increased metabolic demands of this disease, often results in a negative energy balance and occasionally undernutrition or malnutrition. This review summarizes the etiologies and methods for staging pancreatitis, the physiology of pancreatic exocrine secretion and the response of the pancreas to different methods of nutrition support. The results of clinical trials, which examine both parenteral and enteral nutrition in animals and humans with this disease, are reviewed. Recommendations for nutrition management of patients with acute and chronic pancreatitis and areas for future research are discussed.

  9. Management of necrotizing pancreatitis

    PubMed Central

    Slavin, John; Ghaneh, Paula; Sutton, Robert; Hartley, Mark; Rowlands, Peter; Garvey, Conall; Hughes, Mark; Neoptolemos, John

    2001-01-01

    Infection complicating pancreatic necrosis leads to persisting sepsis, multiple organ dysfunction syndrome and accounts for about half the deaths that occur following acute pancreatitis. Severe cases due to gallstones require urgent endoscopic sphincterotomy. Patients with pancreatic necrosis should be followed with serial contrast enhanced computed tomography (CE-CT) and if infection is suspected fine needle aspiration of the necrotic area for bacteriology (FNAB) should be undertaken. Treatment of sterile necrosis should initially be non-operative. In the presence of infection necrosectomy is indicated. Although traditionally this has been by open surgery, minimally invasive procedures are a promising new alternative. There are many unresolved issues in the management of pancreatic necrosis. These include, the use of antibiotic prophylaxis, the precise indications for and frequency of repeat CE-CT and FNAB, and the role of enteral feeding. PMID:11819813

  10. 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, ...

  11. Pancreatic enzyme pharmacotherapy.

    PubMed

    Ferrone, Marcus; Raimondo, Massimo; Scolapio, James S

    2007-06-01

    Supplemental pancreatic enzyme preparations are provided to patients with conditions of pancreatic exocrine deficiency such as chronic pancreatitis and cystic fibrosis. These patients frequently experience steatorrhea, which occurs from inadequate fat absorption. The delivery of sufficient enzyme concentrations into the duodenal lumen simultaneously with meals can reduce nutrient malabsorption, improve the symptoms of steatorrhea, and in some cases alleviate the pain associated with chronic pancreatitis. Current clinical practices dictate administration of lipase 25,000-40,000 units/meal by using pH-sensitive pancrelipase microspheres, along with dosage increases, compliance checks, and differential diagnosis in cases of treatment failure. Despite the large number of specialty enzyme replacements available commercially, many patients remain dissatisfied with standard therapy, and future developments are needed to optimize treatment in these individuals.

  12. 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, ...

  13. Cytokines and acute pancreatitis.

    PubMed

    Brady, M; Christmas, S; Sutton, R; Neoptolemos, J; Slavin, J

    1999-07-01

    Cytokines have been shown to play a pivotal role in multiple organ dysfunction, a major cause of death in severe acute pancreatitis. Moreover, the two-hit hypothesis of the cytokine-induced systemic inflammatory response syndrome explains the variable individual response to severe acute pancreatitis and the impact of secondary events such as sepsis or therapeutic intervention. Many experimental anti-cytokine therapies have been administered following induction of experimental pancreatitis, and have proved to be therapeutic. Patients with severe pancreatitis present early because of pain. Clearly then a window for therapeutic intervention is available between onset of symptoms and peak pro-inflammatory cytokine expression. It is this fundamental observation that convinces many in the field that the treatment of AP will be one of the first clinical successes for novel drugs or therapy that seek to modulate the inflammatory response.

  14. Perspectives in Pancreatic Pain

    PubMed Central

    1997-01-01

    This review describes some of the mechanisms which are thought to be important in the causation of pain in chronic pancreatitis. Both medical and surgical techniques for treating this pain are described. PMID:9298380

  15. 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.

  16. Deciphering Autoimmune Pancreatitis, a Great Mimicker: Case Report and Review of the Literature

    PubMed Central

    Sageer, Mohammed; Sterling, Mark J.

    2015-01-01

    Background. Autoimmune pancreatitis (AIP) is an atypical chronic inflammatory pancreatic disease that appears to involve autoimmune mechanisms. In recent years, AIP has presented as a new clinical entity with its protean pancreaticobiliary and systemic presentations. Its unique pathology and overlap of clinical and radiological features and absence of serological markers foster the disease's unique position. We report a case of diffuse type 1 autoimmune pancreatitis with obstructive jaundice managed with biliary sphincterotomy, stent placement, and corticosteroids. A 50-year-old Caucasian woman presented to our hospital with epigastric pain, nausea, vomiting, and jaundice. Workup showed elevated liver function tests (LFT) suggestive of obstructive jaundice, MRCP done showed diffusely enlarged abnormal appearing pancreas with loss of normal lobulated contours, and IgG4 antibody level was 765 mg/dL. EUS revealed a diffusely hypoechoic and rounded pancreatic parenchyma with distal common bile duct (CBD) stricture and dilated proximal CBD and common hepatic duct (CHD). ERCP showed tight mid to distal CBD stricture that needed dilatation, sphincterotomy, and placement of stent that led to significant improvement in the symptoms and bilirubin level. Based on clinical, radiological, and immunological findings, a definitive diagnosis of AIP was made. Patient was started on prednisone 40 mg/day and she clinically responded in 4 weeks. PMID:25705529

  17. 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

  18. SMAD4-dependent polysome RNA recruitment in human pancreatic cancer cells.

    PubMed

    Thornley, Jessica A; Trask, Heidi W; Ringelberg, Carol S; Ridley, Christian J A; Wang, Sinny; Sal-Lari, Richard Cowper; Moore, Jason H; Korc, Murray; Tomlinson, Craig R

    2012-10-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States because most patients are diagnosed too late in the course of the disease to be treated effectively. Thus, there is a pressing need to more clearly understand how gene expression is regulated in cancer cells and to identify new biomarkers and therapeutic targets. Translational regulation is thought to occur primarily through non-SMAD directed signaling pathways. We tested the hypothesis that SMAD4-dependent signaling does play a role in the regulation of mRNA entry into polysomes and that novel candidate genes in pancreatic cancer could be identified using polysome RNA from the human pancreatic cancer cell line BxPC3 with or without a functional SMAD4 gene. We found that (i) differentially expressed whole cell and cytoplasm RNA levels are both poor predictors of polysome RNA levels; (ii) for a majority of RNAs, differential RNA levels are regulated independently in the nucleus, cytoplasm, and polysomes; (iii) for most of the remaining polysome RNA, levels are regulated via a "tagging" of the RNAs in the nucleus for rapid entry into the polysomes; (iv) a SMAD4-dependent pathway appears to indeed play a role in regulating mRNA entry into polysomes; and (v) a gene list derived from differentially expressed polysome RNA in BxPC3 cells generated new candidate genes and cell pathways potentially related to pancreatic cancer.

  19. 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

  20. 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

  1. 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

  2. Dual Opposing Roles of Metallothionein Overexpression in C57BL/6J Mouse Pancreatic β-Cells

    PubMed Central

    Chen, Suqin; Han, Junying; Liu, Yeqi

    2015-01-01

    Background Growing evidence indicates that oxidative stress (OS), a persistent state of excess amounts of reactive oxygen species (ROS) along with reactive nitrogen species (RNS), plays an important role in insulin resistance, diabetic complications, and dysfunction of pancreatic β-cells. Pancreatic β-cells contain exceptionally low levels of antioxidant enzymes, rendering them susceptible to ROS-induced damage. Induction of antioxidants has been proposed to be a way for protecting β-cells against oxidative stress. Compared to other antioxidants that act against particular β-cell damages, metallothionein (MT) is the most effective in protecting β-cells from several oxidative stressors including nitric oxide, peroxynitrite, hydrogen peroxide, superoxide and streptozotocin (STZ). We hypothesized that MT overexpression in pancreatic β-cells would preserve β-cell function in C57BL/6J mice, an animal model susceptible to high fat diet-induced obesity and type 2 diabetes. Research Design and Methods The pancreatic β-cell specific MT overexpression was transferred to C57BL/6J background by backcrossing. We studied transgenic MT (MT-tg) mice and wild-type (WT) littermates at 8 weeks and 18 weeks of age. Several tests were performed to evaluate the function of islets, including STZ in vivo treatment, intraperitoneal glucose tolerance tests (IPGTT) and plasma insulin levels during IPGTT, pancreatic and islet insulin content measurement, insulin secretion, and islet morphology assessment. Gene expression in islets was performed by quantitative real-time PCR and PCR array analysis. Protein levels in pancreatic sections were evaluated by using immunohistochemistry. Results The transgenic MT protein was highly expressed in pancreatic islets. MT-tg overexpression significantly protected mice from acute STZ-induced ROS at 8 weeks of age; unexpectedly, however, MT-tg impaired glucose stimulated insulin secretion (GSIS) and promoted the development of diabetes. Pancreatic

  3. Transcriptional control of pancreatic endocrine cell development.

    PubMed

    Gasa, Rosa

    2005-11-01

    In diabetes mellitus, insulin-producing beta cells in the pancreas are lost (type 1) or dysfunctional (type 2). Cell replacement therapy has emerged as a promising alternative to insulin injection for treatment of diabetic patients. Given the scarcity and difficulty in obtaining pancreatic beta cells from cadaveric donors, current research is aiming at the generation of functional beta cells from non-beta-cell sources or from pluripotent progenitors such as adult or embryonic stem cells. However, to achieve this, we first need to understand how beta cells are formed during normal development. Knowledge of the molecular and genetic pathways that direct cells along their differentiation pathway will be instrumental if we aim to engineer new beta cells for clinical use. This article reviews pancreatic development from a gene expression point of view and discusses our current understanding of the transcription factors that rule pancreatic morphogenesis during ontogeny.

  4. [Hereditary aspects of pancreatitis].

    PubMed

    Bak, Daniel; Sobczyńska-Tomaszewska, Agnieszka; Bal, Jerzy

    2003-01-01

    Pancreatitis presents clinically as acute and chronic form. A common characteristic of these two forms is enzymatic autodigestion of pancreas in the course of the disease. It results from premature activation of pancreatic digestive enzymes and disturbance of subtle balance between proteolytic enzymes and their inhibitors. The way to understand the character of mechanisms leading to development of pancreatitis has been simplified by discovery of genetic factors, which are able to initiate pathological changes at tissue level. Mutations in the PRSS1 gene (first of all R122H and N29I mutations), which encodes for cationic trypsin, cause trypsin to be protected from autodegradation. These mutations also cause precursor of trypsin - trypsinogen, to be activated easier. On the other hand mutations in the SPINK1 gene have been identified. SPINK1 gene encodes for the most important protease inhibitor of the pancreatic fluid. The most frequent mutation, namely N34S, decrease SPINK1 protein in its activity. The link between the genotype and phenotype is not clear in every case. It is probable that pancreatitis will be recognized as poligenic with many genes engaged in the disease development. Pancreatic cancer is a frequent consequence of pancreatitis. It is a very invasive cancer with high mortality. In the course of pancreatic inflammation intensive cell proliferation takes place for regeneration of pancreas damage. It is the chance for amplification of pathological changes in DNA, which have arisen as a ROS's (Reactive Oxygen Species) and RNOS's (Reactive Nitrogen Oxide Species) action effect. ROS and RNOS are generated in the course of pancreas inflammation.

  5. [Biochemical diagnostics in acute pancreatitis recognition and outcome predicition].

    PubMed

    Olczyk, Paweł; Kozma, Ewa M; Olczyk, Krystyna; Komosińska-Vassev, Katarzyna

    2004-01-01

    Acute pancreatitis (AP) is a common disease associated with an improper activation of pancreatic zymogens leading to autodigestion of the gland and if excessive--to multiple organ dysfunction. Acute necrotizing pancreatitis manifested by 20% of patients with acute pancreatitis is a life threatening disorder requiring subsequent management in intensive care unit. Unfortunately, none of biochemical tests presently used for laboratory assessment of acute pancreatitis at the early stage of the disease is able to estimate accurately: diagnosis, etiology and severity. At present, diagnosis of acute pancreatitis is based on evaluation of serum amylase and lipase activity due to easy availability and simplicity of these enzymatic tests. Low specificity of the mentioned enzymes resulted in studies concerning pancreatic isoamylase, elastase-1, chymotrypsine, procarboxy-peptidase B, trypsinogen-2 and immunoreactive trypsinogen usefulness in the laboratory diagnosis of AP. The prediction of severity in acute pancreatitis using multifactorial scoring systems is cumbersome especially due to their complexity. On the other hand the biochemical method of choice, estimation of serum C reactive protein, is useless in the early phase of disease. Unfortunately, the computed tomography--the most accurate method in severity assessing--is not always available. Recent studies have brought some progress in severity predicting, such as phospholipase A2, cellular immunity markers, cytokines, activation peptides of trypsinogen and carboxypeptidase B, procalcitonine, pancreatitis associated protein and serum amyloid A. All these newly introduced biochemical methods allow to look optimistically into the future of laboratory diagnostics of the acute pancreatitis believing that the problem of diagnosing and predicting the AP severity will be solved. PMID:15850341

  6. [Biochemical diagnostics in acute pancreatitis recognition and outcome predicition].

    PubMed

    Olczyk, Paweł; Kozma, Ewa M; Olczyk, Krystyna; Komosińska-Vassev, Katarzyna

    2004-01-01

    Acute pancreatitis (AP) is a common disease associated with an improper activation of pancreatic zymogens leading to autodigestion of the gland and if excessive--to multiple organ dysfunction. Acute necrotizing pancreatitis manifested by 20% of patients with acute pancreatitis is a life threatening disorder requiring subsequent management in intensive care unit. Unfortunately, none of biochemical tests presently used for laboratory assessment of acute pancreatitis at the early stage of the disease is able to estimate accurately: diagnosis, etiology and severity. At present, diagnosis of acute pancreatitis is based on evaluation of serum amylase and lipase activity due to easy availability and simplicity of these enzymatic tests. Low specificity of the mentioned enzymes resulted in studies concerning pancreatic isoamylase, elastase-1, chymotrypsine, procarboxy-peptidase B, trypsinogen-2 and immunoreactive trypsinogen usefulness in the laboratory diagnosis of AP. The prediction of severity in acute pancreatitis using multifactorial scoring systems is cumbersome especially due to their complexity. On the other hand the biochemical method of choice, estimation of serum C reactive protein, is useless in the early phase of disease. Unfortunately, the computed tomography--the most accurate method in severity assessing--is not always available. Recent studies have brought some progress in severity predicting, such as phospholipase A2, cellular immunity markers, cytokines, activation peptides of trypsinogen and carboxypeptidase B, procalcitonine, pancreatitis associated protein and serum amyloid A. All these newly introduced biochemical methods allow to look optimistically into the future of laboratory diagnostics of the acute pancreatitis believing that the problem of diagnosing and predicting the AP severity will be solved.

  7. Pathological and Molecular Evaluation of Pancreatic Neoplasms

    PubMed Central

    Rishi, Arvind; Goggins, Michael; Wood, Laura D.; Hruban, Ralph H.

    2015-01-01

    Pancreatic neoplasms are morphologically and genetically heterogeneous and include wide variety of neoplasms ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecular pathogenesis brings in new opportunities for early detection, improved prognostication, and personalized gene-specific therapies. Here we review the pathological classification of pancreatic neoplasms from their molecular and genetic perspective. All of the major tumor types that arise in the pancreas have been sequenced, and a new classification that incorporates molecular findings together with pathological findings is now possible (Table 1). This classification has significant implications for our understanding of why tumors aggregate in some families, for the development of early detection tests, and for the development of personalized therapies for patients with established cancers. Here we describe this new classification using the framework of the standard histological classification. PMID:25726050

  8. Tropical chronic pancreatitis

    PubMed Central

    Barman, K; Premalatha, G; Mohan, V

    2003-01-01

    Tropical chronic pancreatitis (TCP) is a juvenile form of chronic calcific non-alcoholic pancreatitis, seen almost exclusively in the developing countries of the tropical world. The classical triad of TCP consists of abdominal pain, steatorrhoea, and diabetes. When diabetes is present, the condition is called fibrocalculous pancreatic diabetes (FCPD) which is thus a later stage of TCP. Some of the distinctive features of TCP are younger age at onset, presence of large intraductal calculi, more aggressive course of the disease, and a high susceptibility to pancreatic cancer. Pancreatic calculi are the hallmark for the diagnosis of TCP and in non-calcific cases ductal dilation on endoscopic retrograde cholangiopancreatography, computed tomography, or ultrasound helps to identify the disease. Diabetes is usually quite severe and of the insulin requiring type, but ketosis is rare. Microvascular complications of diabetes occur as frequently as in type 2 diabetes but macrovascular complications are uncommon. Pancreatic enzyme supplements are used for relief of abdominal pain and reducing the symptoms related to steatorrhoea. Early diagnosis and better control of the endocrine and exocrine dysfunction could help to ensure better survival and improve the prognosis and quality of life of TCP patients. PMID:14654569

  9. Hereditary pancreatitis: current perspectives.

    PubMed

    Raphael, Kara L; Willingham, Field F

    2016-01-01

    Hereditary pancreatitis (HP) is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life) and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy. PMID:27555793

  10. Hereditary pancreatitis: current perspectives

    PubMed Central

    Raphael, Kara L; Willingham, Field F

    2016-01-01

    Hereditary pancreatitis (HP) is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life) and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy. PMID:27555793

  11. Nutrition in pancreatic diseases.

    PubMed

    Meier, Rémy F; Beglinger, Christoph

    2006-01-01

    The pancreas plays a major role in nutrient digestion. Therefore, in both acute and chronic pancreatitis, exocrine and endocrine pancreatic insufficiency can develop, impairing digestive and absorptive processes. These changes can lead to malnutrition over time. In parallel to these changes, decreased caloric intake and increased metabolic activity are often present. Nutritional deficiencies negatively affect outcome if they are not treated. Nutritional assessment and the clinical severity of the disease are important for planning any nutritional intervention. In severe acute pancreatitis, enteral nutrition with a naso-jejunal feeding tube and a low molecular diet displays clear advantages compared to parenteral nutrition. Infectious complications, length of hospital stay and the need for surgery are reduced. Furthermore, enteral nutrition is less costly than parenteral nutrition. Parenteral nutrition is reserved for patients who do not tolerate enteral nutrition. Abstinence from alcohol, dietary modifications and pancreatic enzyme supplementation is sufficient in over 80% of patients with chronic pancreatitis. In addition, oral supplements are helpful. Enteral nutrition can be necessary if weight loss continues. Parenteral nutrition is very seldom used in patients with chronic pancreatitis.

  12. Hereditary pancreatitis: current perspectives.

    PubMed

    Raphael, Kara L; Willingham, Field F

    2016-01-01

    Hereditary pancreatitis (HP) is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life) and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy.

  13. Effects of Local Pancreatic Renin-Angiotensin System on the Microcirculation of Rat with Severe Acute Pancreatitis.

    PubMed

    Pan, Zhijian; Feng, Ling; Long, Haocheng; Wang, Hui; Feng, Jiarui; Chen, Feixiang

    2015-07-01

    Severe acute pancreatitis (SAP) is normally related to multiorgan dysfunction and local complications. Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP. The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction. Rats in the sham group were injected with normal saline in identical locations. We also investigated the regulation of experimentally induced SAP on local RAS expression in the pancreas through determination of the activities of serum amylase, lipase and myeloperoxidase, histological and biochemical analysis, radioimmunoassay, fluorescence quantitative PCR and Western blot analysis. The results indicated that valsartan could effectively suppress the local RAS to protect against experimental acute pancreatitis through inhibition of microcirculation disturbances and inflammation. The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists. Moreover, other RAS inhibitors could be a new therapeutic target in acute pancreatitis. PMID:26170733

  14. Silencing Mist1 Gene Expression Is Essential for Recovery from Acute Pancreatitis

    PubMed Central

    Karki, Anju; Humphrey, Sean E.; Steele, Rebecca E.; Hess, David A.; Taparowsky, Elizabeth J.; Konieczny, Stephen F.

    2015-01-01

    Acinar cells of the exocrine pancreas are tasked with synthesizing, packaging and secreting vast quantities of pro-digestive enzymes to maintain proper metabolic homeostasis for the organism. Because the synthesis of high levels of hydrolases is potentially dangerous, the pancreas is prone to acute pancreatitis (AP), a disease that targets acinar cells, leading to acinar-ductal metaplasia (ADM), inflammation and fibrosis—events that can transition into the earliest stages of pancreatic ductal adenocarcinoma. Despite a wealth of information concerning the broad phenotype associated with pancreatitis, little is understood regarding specific transcriptional regulatory networks that are susceptible to AP and the role these networks play in acinar cell and exocrine pancreas responses. In this study, we examined the importance of the acinar-specific maturation transcription factor MIST1 to AP damage and organ recovery. Analysis of wild-type and Mist1 conditional null mice revealed that Mist1 gene transcription and protein accumulation were dramatically reduced as acinar cells underwent ADM alterations during AP episodes. To test if loss of MIST1 function was primarily responsible for the damaged status of the organ, mice harboring a Cre-inducible Mist1 transgene (iMist1) were utilized to determine if sustained MIST1 activity could alleviate AP damage responses. Unexpectedly, constitutive iMist1 expression during AP led to a dramatic increase in organ damage followed by acinar cell death. We conclude that the transient silencing of Mist1 expression is critical for acinar cells to survive an AP episode, providing cells an opportunity to suppress their secretory function and regenerate damaged cells. The importance of MIST1 to these events suggests that modulating key pancreas transcription networks could ease clinical symptoms in patients diagnosed with pancreatitis and pancreatic cancer. PMID:26717480

  15. Vestibular Function Tests for Vestibular Migraine: Clinical Implication of Video Head Impulse and Caloric Tests

    PubMed Central

    Kang, Woo Seok; Lee, Sang Hun; Yang, Chan Joo; Ahn, Joong Ho; Chung, Jong Woo; Park, Hong Ju

    2016-01-01

    Vestibular migraine (VM) is one of the most common causes of episodic vertigo. We reviewed the results of multiple vestibular function tests in a cohort of VM patients who were diagnosed with VM according to the diagnostic criteria of the Barany Society and the International Headache Society and assessed the efficacy of each for predicting the prognosis in VM patients. A retrospective chart analysis was performed on 81 VM patients at a tertiary care center from June 2014 to July 2015. Patients were assessed by the video head impulse test (vHIT), caloric test, vestibular-evoked myogenic potentials (VEMPs), and sensory organization test (SOT) at the initial visit and then evaluated for symptomatic improvement after 6 months. Complete response (CR) was defined as no need for continued medication, partial response (PR) as improved symptoms but need for continued medication, and no response (NR) as no symptomatic improvement and requiring increased dosage or change in medications. At the initial evaluation, 9 of 81 patients (11%) exhibited abnormal vHIT results, 14 of 73 (19%) exhibited abnormal caloric test results, 25 of 65 (38%) exhibited abnormal SOT results, 8 of 75 (11%) exhibited abnormal cervical VEMP results, and 20 of 75 (27%) exhibited abnormal ocular VEMP results. Six months later, 63 of 81 patients (78%) no longer required medication (CR), while 18 (22%) still required medication, including 7 PR and 11 NR patients. Abnormal vHIT gain and abnormal caloric results were significantly related to the necessity for continued medication at 6-month follow-up (OR = 5.67 and 4.36, respectively). Abnormal vHIT and caloric test results revealed semicircular canal dysfunction in VM patients and predicted prolonged preventive medication requirement. These results suggest that peripheral vestibular abnormalities are closely related to the development of vertigo in VM patients. PMID:27746761

  16. ROC and Loss Function Analysis in Sequential Testing

    ERIC Educational Resources Information Center

    Muijtjens, Arno M. M.; Van Luijk, Scheltus J.; Van Der Vleuten, Cees P. M.

    2006-01-01

    Sequential testing is applied to reduce costs in SP-based tests (OSCEs). Initially, all candidates take a screening test consisting of a part of the OSCE. Candidates who fail the screen sit the complete test, whereas those who pass the screen are qualified as a pass of the complete test. The procedure may result in a reduction of testing…

  17. Measurement of global functional performance in patients with rheumatoid arthritis using rheumatology function tests.

    PubMed

    Escalante, Agustín; Haas, Roy W; del Rincón, Inmaculada

    2004-01-01

    Outcome assessment in patients with rheumatoid arthritis (RA) includes measurement of physical function. We derived a scale to quantify global physical function in RA, using three performance-based rheumatology function tests (RFTs). We measured grip strength, walking velocity, and shirt button speed in consecutive RA patients attending scheduled appointments at six rheumatology clinics, repeating these measurements after a median interval of 1 year. We extracted the underlying latent variable using principal component factor analysis. We used the Bayesian information criterion to assess the global physical function scale's cross-sectional fit to criterion standards. The criteria were joint tenderness, swelling, and deformity, pain, physical disability, current work status, and vital status at 6 years after study enrolment. We computed Guyatt's responsiveness statistic for improvement according to the American College of Rheumatology (ACR) definition. Baseline functional performance data were available for 777 patients, and follow-up data were available for 681. Mean +/- standard deviation for each RFT at baseline were: grip strength, 14 +/- 10 kg; walking velocity, 194 +/- 82 ft/min; and shirt button speed, 7.1 +/- 3.8 buttons/min. Grip strength and walking velocity departed significantly from normality. The three RFTs loaded strongly on a single factor that explained >or=70% of their combined variance. We rescaled the factor to vary from 0 to 100. Its mean +/- standard deviation was 41 +/- 20, with a normal distribution. The new global scale had a stronger fit than the primary RFT to most of the criterion standards. It correlated more strongly with physical disability at follow-up and was more responsive to improvement defined