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Sample records for pancreatic function test

  1. Pancreatic exocrine function testing

    SciTech Connect

    Goff, J.S.

    1981-11-01

    It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of all these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weaknesses of each.

  2. Defining the Accuracy of Secretin Pancreatic Function Testing in Patients With Suspected Early Chronic Pancreatitis

    PubMed Central

    Ketwaroo, Gyanprakash; Brown, Alphonso; Young, Benjamin; Kheraj, Rakhi; Sawhney, Mandeep; Mortele, Koenraad J.; Najarian, Robert; Tewani, Sumeet; Dasilva, Deborah; Freedman, Steven; Sheth, Sunil

    2017-01-01

    OBJECTIVES The diagnosis of chronic pancreatitis in patients with characteristic symptoms but normal pancreatic imaging is challenging. Assessment of pancreatic function through secretin pancreatic function testing (SPFT) has been advocated in this setting, but its diagnostic accuracy is not fully known. METHODS This was a retrospective review of patients who received SPFT at our tertiary care institution between January 1995 and December 2008 for suspected chronic pancreatitis. For all patients, medical records were reviewed for evidence of subsequent development of chronic pancreatitis by imaging and/or pathology. Patients were then categorized as “true positive” or “true negative” for chronic pancreatitis based on follow-up imaging or histologic evidence. RESULTS In all, 116 patients underwent SPFT. Of the 27 patients who tested positive, 7 were lost to follow-up. Of the remaining 20 SPFT-positive patients, 9 (45 %) developed radiologic or histologic evidence of chronic pancreatitis after a median of 4 years (1–11 years). Of the 89 patients who had negative SPFT testing, 19 were lost to follow-up. Of the remaining 70 patients, 2 were eventually diagnosed with chronic pancreatitis based on subsequent imaging/histology after a median follow-up period of 7 years (3–11 years). The sensitivity of the SPFT in diagnosing chronic pancreatitis was 82 % with a specificity of 86 %. The positive predictive value (PPV) of chronic pancreatitis was 45 % with a negative predictive value (NPV) of 97 %. CONCLUSIONS In patients with suspected early chronic pancreatitis and normal pancreatic imaging, SPFT is highly accurate at ruling out early chronic pancreatitis with a NPV of 97 %. PMID:23711627

  3. Pancreatic function in Crohn's disease.

    PubMed Central

    Hegnhøj, J; Hansen, C P; Rannem, T; Søbirk, H; Andersen, L B; Andersen, J R

    1990-01-01

    We investigated exocrine pancreatic function in a population of patients with Crohn's disease in order to correlate the pancreatic function with clinical and laboratory variables. A total of 143 patients affected by Crohn's disease and 115 control subjects were studied. All had a Lundh meal test. As a group patients with Crohn's disease had significantly decreased activity of both amylase (p less than 0.02) and lipase (p less than 0.001) in duodenal aspirates. In patients with Crohn's disease enzyme activities were not correlated to duration of disease or to extent or localisation of previous bowel resection. The lowest enzyme values were found in patients with the most extensive bowel involvement, and they were significantly lower (p less than 0.05) than in patients with disease confined to the terminal ileum. The differences between enzyme values in other subgroups of patients were not significant. For the patient group as a whole no correlation was found between disease activity and enzyme values, but for the most uniform group of patients, those with terminal ileitis, pancreatic function was significantly lower (p less than 0.05) in patients with moderate and severe disease compared with patients with mild disease. Thus at least two factors seem to be responsible for impaired pancreatic function in Crohn's disease: firstly disease activity and secondly localisation or extent of disease. PMID:1698692

  4. 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

  5. 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 ...

  6. 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

  7. 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

  8. Pancreatic function in chronic inflammatory bowel disease.

    PubMed

    Angelini, G; Cavallini, G; Bovo, P; Brocco, G; Castagnini, A; Lavarini, E; Merigo, F; Tallon, N; Scuro, L A

    1988-03-01

    This study was prospectively carried out to evaluate the frequency and clinical significance of pancreatic impairment in the course of chronic inflammatory bowel disease (CIBD). Twenty-seven patients affected by ulcerative colitis or Crohn's disease were submitted to a secretin-cerulein test, oral glucose test (OGT) and to indirect immunofluorescence (IFL) for detection of autoantibodies against exocrine and endocrine tissue. A bicarbonate plus enzyme or only an enzyme insufficiency was found in 11/27 patients, whereas isolated lipase decrease was observed in 18 subjects. In the results of the OGT and the indirect IFL test there was no difference between patients and controls. These data demonstrate that pancreatic impairment is a far more frequent occurrence than generally recognized in clinical practice. The decrease of lipase secretion could worsen the consequences of malabsorption in Crohn's disease of the small intestine. Therefore we think that a pancreatic assessment is advisable, at least in Crohn's disease patients with steatorrhea.

  9. Small amounts of tissue preserve pancreatic function

    PubMed Central

    Lu, Zipeng; Yin, Jie; Wei, Jishu; Dai, Cuncai; Wu, Junli; Gao, Wentao; Xu, Qing; Dai, Hao; Li, Qiang; Guo, Feng; Chen, Jianmin; Xi, Chunhua; Wu, Pengfei; Zhang, Kai; Jiang, Kuirong; Miao, Yi

    2016-01-01

    Abstract Middle-segment preserving pancreatectomy (MPP) is a novel procedure for treating multifocal lesions of the pancreas while preserving pancreatic function. However, long-term pancreatic function after this procedure remains unclear. The aims of this current study are to investigate short- and long-term outcomes, especially long-term pancreatic endocrine function, after MPP. From September 2011 to December 2015, 7 patients underwent MPP in our institution, and 5 cases with long-term outcomes were further analyzed in a retrospective manner. Percentage of tissue preservation was calculated using computed tomography volumetry. Serum insulin and C-peptide levels after oral glucose challenge were evaluated in 5 patients. Beta-cell secreting function including modified homeostasis model assessment of beta-cell function (HOMA2-beta), area under the curve (AUC) for C-peptide, and C-peptide index were evaluated and compared with those after pancreaticoduodenectomy (PD) and total pancreatectomy. Exocrine function was assessed based on questionnaires. Our case series included 3 women and 2 men, with median age of 50 (37–81) years. Four patients underwent pylorus-preserving PD together with distal pancreatectomy (DP), including 1 with spleen preserved. The remaining patient underwent Beger procedure and spleen-preserving DP. Median operation time and estimated intraoperative blood loss were 330 (250–615) min and 800 (400–5500) mL, respectively. Histological examination revealed 3 cases of metastatic lesion to the pancreas, 1 case of chronic pancreatitis, and 1 neuroendocrine tumor. Major postoperative complications included 3 cases of delayed gastric emptying and 2 cases of postoperative pancreatic fistula. Imaging studies showed that segments representing 18.2% to 39.5% of the pancreas with good blood supply had been preserved. With a median 35.0 months of follow-ups on pancreatic functions, only 1 patient developed new-onset diabetes mellitus of the 4

  10. Potential for Screening for Pancreatic Exocrine Insufficiency Using the Fecal Elastase-1 Test.

    PubMed

    Domínguez-Muñoz, J Enrique; D Hardt, Philip; Lerch, Markus M; Löhr, Matthias J

    2017-03-17

    The early diagnosis of pancreatic exocrine insufficiency (PEI) is hindered because many of the functional diagnostic techniques used are expensive and require specialized facilities, which prevent their widespread availability. We have reviewed current evidence in order to compare the utility of these functional diagnostic techniques with the fecal elastase-1 (FE-1) test in the following three scenarios: screening for PEI in patients presenting with symptoms suggestive of pancreatic disease, such as abdominal pain or diarrhea; determining the presence of PEI in patients with an established diagnosis of pancreatic disease, such as chronic pancreatitis or cystic fibrosis; determining exocrine status in disorders not commonly tested for PEI, but which have a known association with this disorder. Evidence suggests the FE-1 test is reliable for the evaluation of pancreatic function in many pancreatic and non-pancreatic disorders. It is non-invasive, is less time-consuming, and is unaffected by pancreatic enzyme replacement therapy. Although it cannot be considered the gold-standard method for the functional diagnosis of PEI, the advantages of the FE-1 test make it a very appropriate test for screening patients who may be at risk of this disorder.

  11. Influence of high intensity focused ultrasound (HIFU) treatment to the pancreatic function in pancreatic cancer patients.

    PubMed

    Shi, Yulan; Ying, Xiao; Hu, Xiaoye; Zhao, Jing; Fang, Xuefeng; Wu, Minghui; Chen, Tian Zhou; Shen, Hong

    2015-05-01

    Present study was designed to investigate the pancreatic endocrine and exocrine function damage after High Intensity Focused Ultrasound (HIFU) therapy in patients with advanced pancreatic cancer. It was a retrospective analysis of blood glucose and amylase changes in 59 advanced pancreatic cancer patients treated with HIFU from 2010 February to 2014 January. The mean glucose and amylase before HIFU treatment were 6.02mmol/L and 59.17 U/L respectively. After HIFU treatment, it was shown that the mean glucose and amylase levels were 5.66mmol/L and 57.86/L respectively. There was no statistical significance between them. No acute pancreatitis was observed. The endocrine and exocrine function of pancreatic cancer patients was not damaged by HIFU treatment. HIFU treatment for the pancreatic cancer patients seems to be safe.

  12. Clock genes, pancreatic function, and diabetes.

    PubMed

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

    2014-12-01

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

  13. 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.

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

    PubMed Central

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

    2016-01-01

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

  15. Pancreatic functions in high salt fed female rats

    PubMed Central

    Lasheen, Noha N

    2015-01-01

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

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

    SciTech Connect

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

    1986-05-01

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

  17. 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.

  18. Impaired Pancreatic Beta Cell Function by Chronic Intermittent Hypoxia

    PubMed Central

    Wang, Ning; Khan, Shakil A.; Prabhakar, Nanduri R.; Nanduri, Jayasri

    2013-01-01

    Breathing disorders with recurrent apnea produce periodic decreases in arterial blood O2 or chronic intermittent hypoxia (CIH). Recurrent apnea patients and CIH-exposed rodents exhibit several co-morbidities including diabetes. However, the effects of CIH on pancreatic beta cell function are not known. In the present study, we investigated pancreatic beta cell function in C57BL6 mice exposed to 30 days of CIH. CIH-exposed mice exhibited elevated levels of fasting plasma insulin, but comparable glucose levels, and higher homeostasis model assessment (HOMA), indicating insulin resistance. Pancreatic beta cell morphology was unaltered in CIH- exposed mice. Insulin content was decreased in CIH-exposed beta cells, and this effect was associated with increased proinsulin levels. mRNA and protein levels of the enzyme pro-hormone convertase 1 (PC1) which converts proinsulin to insulin were down regulated in CIH-treated islets. More importantly, glucose-stimulated insulin secretion (GSIS) was impaired in CIH-exposed mice and in isolated islets. Mitochondrial reactive oxygen species (ROS) levels were elevated in CIH-exposed pancreatic islets. Treatment of mice with mito-tempol, a scavenger of mitochondrial ROS during CIH exposure, prevented the augmented insulin secretion and restored the proinsulin as well as HOMA values to control levels. These results demonstrate that CIH leads to pancreatic beta cell dysfunction manifested by augmented basal insulin secretion, insulin resistance, defective proinsulin processing, impaired GSIS and mitochondrial ROS mediates the effects of CIH on pancreatic beta cell function. PMID:23709585

  19. Evaluation of serum feline pancreatic lipase immunoreactivity and helical computed tomography versus conventional testing for the diagnosis of feline pancreatitis.

    PubMed

    Forman, M A; Marks, S L; De Cock, H E V; Hergesell, E J; Wisner, E R; Baker, T W; Kass, P H; Steiner, J M; Williams, D A

    2004-01-01

    Serum feline trypsinogen-like immunoreactivity (fTLI) concentrations and abdominal ultrasound have facilitated the noninvasive diagnosis of pancreatitis in cats, but low sensitivities (33% and 20-35%, respectively) have been reported. A radioimmunoassay has been validated to measure feline pancreatic lipase immunoreactivity (fPLI), but the assay's sensitivity and specificity have not been established. In human beings, the sensitivity of computed tomography (CT) is high (75-90%), but in a study of 10 cats, only 2 had CT changes suggestive of pancreatitis. We prospectively evaluated these diagnostic tests in cats with and without pancreatitis. In all cats, serum was obtained for fTLI and fPLI concentrations, and pancreatic ultrasound images and biopsies were acquired. Serum fPLI concentrations (P< .0001) and ultrasound findings (P = .0073) were significantly different between healthy cats and cats with pancreatitis. Serum fTLI concentrations (P = .15) and CT measurements (P = .18) were not significantly different between the groups. The sensitivity of fTLI in cats with moderate to severe pancreatitis was 80%, and the specificity in healthy cats was 75%. Feline PLI concentrations were both sensitive in cats with moderate to severe pancreatitis (100%) and specific in the healthy cats (100%). Abdominal ultrasound was both sensitive in cats with moderate to severe pancreatitis (80%) and specific in healthy cats (88%). The high sensitivities of fPLI and abdominal ultrasound suggest that these tests should play an important role in the noninvasive diagnosis of feline pancreatitis. As suggested by a previous study, pancreatic CT is not a useful diagnostic test for feline pancreatitis.

  20. 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

  1. Progressive loss of pancreatic function in chronic pancreatitis is delayed by main pancreatic duct decompression. A longitudinal prospective analysis of the modified puestow procedure.

    PubMed Central

    Nealon, W H; Thompson, J C

    1993-01-01

    OBJECTIVE: This study evaluated the effect of operative drainage of the main pancreatic duct (MPD) on functional derangements associated with chronic pancreatitis (CP). SUMMARY BACKGROUND DATA: The author previously reported delayed functional impairment in an evaluation of the impact of operative drainage in patients with CP. The author now reports on a prospective study of 143 patients with this diagnosis. METHODS: Each patient underwent 1) ERCP, 2) the Bentiromide PABA, 3) 72-hour fecal fat test, 4) oral glucose tolerance test (OGTT) and 5) fat meal (LIPOMUL)--stimulated pancreatic polypeptide release (PP). All patients were stratified as mild/moderate (M/M) or severe CP on the basis of a 5-point system that was developed by the author. Patients were studied at 16-month intervals. RESULTS: All 143 patients underwent initial and follow-up evaluations in a mean follow-up of 47.3 months; 83 of 143 patients had M/M grade at initial evaluation. Eighty-seven patients underwent (MPD) decompression to relieve abdominal pain. In a separate prospective 17 patients with a diagnosis of CP, a grade of M/M and non-disabling abdominal pain were randomized to operative or non-operative treatment; 9 of these randomized patients were operated upon and 8 were not. No patient improved their grade during follow-up; 47 of 83 M/M patients had operative drainage and 36 did not. This grade was preserved in 41 of 47 (87%) operated patients but in only 8 of the 36 non-operated patients (22%). In the randomized trial, seven of nine operated patients retained their functional status in follow-up, whereas only two of eight patients (25%) randomized to non-operation preserved their functional grade. CONCLUSIONS: These data in this large study as well as among a previous randomized sample, support a policy of early operative drainage before the development of irreversible functional impairment in patients with chronic pancreatitis and associated dilation of the main pancreatic duct. PMID

  2. 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

    2015-04-07

    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.

  3. Functions of autophagy in hepatic and pancreatic physiology and disease.

    PubMed

    Czaja, Mark J

    2011-06-01

    Autophagy is a lysosomal pathway that degrades and recycles intracellular organelles and proteins to maintain energy homeostasis during times of nutrient deprivation and to remove damaged cell components. Recent studies have identified new functions for autophagy under basal and stressed conditions. In the liver and pancreas, autophagy performs the standard functions of degrading mitochondria and aggregated proteins and regulating cell death. In addition, autophagy functions in these organs to regulate lipid accumulation in hepatic steatosis, trypsinogen activation in pancreatitis, and hepatitis virus replication. This review discusses the effects of autophagy on hepatic and pancreatic physiology and the contribution of this degradative process to diseases of these organs. The discovery of novel functions for this lysosomal pathway has increased our understanding of the pathophysiology of diseases in the liver and pancreas and suggested new possibilities for their treatment.

  4. Pancreatitis

    MedlinePlus

    ... removal is sometimes performed along with a sphincterotomy. Stent placement. Using the endoscope, the doctor places a ... a narrowed pancreatic or bile duct. A temporary stent may be placed for a few months to ...

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

    PubMed Central

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

    2015-01-01

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

  6. Differential associations of oral glucose tolerance test-derived measures of insulin sensitivity and pancreatic β-cell function with coronary artery calcification and microalbuminuria in type 2 diabetes.

    PubMed

    Mulvey, Claire K; McNeill, Ann M; Girman, Cynthia J; Churchill, Timothy W; Terembula, Karen; Ferguson, Jane F; Shah, Rachana; Mehta, Nehal N; Qasim, Atif N; Rickels, Michael R; Reilly, Muredach P

    2014-01-01

    OBJECTIVE We evaluated relationships of oral glucose tolerance testing (OGTT)-derived measures of insulin sensitivity and pancreatic β-cell function with indices of diabetes complications in a cross-sectional study of patients with type 2 diabetes who are free of overt cardiovascular or renal disease. RESEARCH DESIGN AND METHODS A subset of participants from the Penn Diabetes Heart Study (n = 672; mean age 59 ± 8 years; 67% male; 60% Caucasian) underwent a standard 2-h, 75-g OGTT. Insulin sensitivity was estimated using the Matsuda Insulin Sensitivity Index (ISI), and β-cell function was estimated using the Insulinogenic Index. Multivariable modeling was used to analyze associations between quartiles of each index with coronary artery calcification (CAC) and microalbuminuria. RESULTS The Insulinogenic Index and Matsuda ISI had distinct associations with cardiometabolic risk factors. The top quartile of the Matsuda ISI had a negative association with CAC that remained significant after adjusting for traditional cardiovascular risk factors (Tobit ratio -0.78 [95% CI -1.51 to -0.05]; P = 0.035), but the Insulinogenic Index was not associated with CAC. Conversely, the highest quartile of the Insulinogenic Index, but not the Matsuda ISI, was associated with lower odds of microalbuminuria (OR 0.52 [95% CI 0.30-0.91]; P = 0.022); however, this association was attenuated in models that included duration of diabetes. CONCLUSIONS Lower β-cell function is associated with microalbuminuria, a microvascular complication, while impaired insulin sensitivity is associated with higher CAC, a predictor of macrovascular complications. Despite these pathophysiological insights, the Matsuda ISI and Insulinogenic Index are unlikely to be translated into clinical use in type 2 diabetes beyond established clinical variables, such as obesity or duration of diabetes.

  7. Functional Improvement in Rats' Pancreatic Islets Using Magnesium Oxide Nanoparticles Through Antiapoptotic and Antioxidant Pathways.

    PubMed

    Moeini-Nodeh, Shermineh; Rahimifard, Mahban; Baeeri, Maryam; Abdollahi, Mohammad

    2017-01-01

    According to undiscovered toxicity and safety of magnesium oxide nanoparticles (MgO NPs) in isolated pancreatic islet cells, this study was designed to examine the effects of its various concentrations on a time-course basis on the oxidative stress, viability, and function of isolated islets of rat's pancreas. Pancreatic islets were isolated and exposed to different MgO NP (<100 nm) concentrations within three different time points. After that, oxidative stress biomarkers were investigated and the best exposure time was selected. Then, safety of MgO NPs was investigated by flow cytometry and fluorescent staining, and levels of insulin secretion and caspase activity were measured. The results illustrated a considerable decrease in oxidative stress markers such as reactive oxygen species (ROS) and lipid peroxidation (LPO) levels of pancreatic islets which were treated by MgO NPs for 24 h. Also, in that time of exposure, cell apoptosis investigation by flow cytometry and insulin test showed that MgO NPs, in a concentration of 100 μg/ml, decreased the rate of apoptotic cells via inhibiting caspase-9 activity and made a significant increase in the level of insulin secretion. Data of function and apoptosis biomarkers correlated with each other. It is concluded that the use of MgO NPs in concentration of as low as 100 μg/ml can induce antiapoptotic, antioxidative, and antidiabetic effects in rat pancreatic islets, which support its possible benefit in islet transplantation procedures.

  8. 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

  9. 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 ...

  10. Liver function tests

    MedlinePlus

    Liver function tests are common tests that are used to see how well the liver is working. Tests include: ... M, Bowne WB, Bluth MH. Evaluation of liver function. In: McPherson RA, Pincus MR, eds. Henry's Clinical ...

  11. The effect of maternal caffeine ingestion on pancreatic function in the neonatal rat.

    PubMed

    Dunlop, M; Larkins, R G; Court, J M

    1982-10-01

    Pancreatic function was investigated in neonatal suckling offspring of caffeine-ingesting dams, with or without maternal sucrose supplementation, throughout pregnancy and lactation. In offspring of rats ingesting caffeine without sucrose supplementation, there was initial hyperinsulinaemia, followed by a progressive fall of plasma insulin to subnormal levels. This fall in plasma insulin coincided with depletion of pancreatic insulin stores. Both the fall in plasma insulin and depletion of pancreatic insulin stores were prevented by sucrose supplementation of caffeine-ingesting dams. Offspring of dams fed sucrose alone and control offspring also maintained pancreatic insulin stores and circulating insulin levels over the first 14 days of postnatal life. Pancreases from offspring of caffeine-exposed animals tested in vitro showed enhanced sensitivity of the insulin release process to glucose. This was reflected in the glucose concentration required to elicit half-maximal insulin release (2.4 +/- 0.2 mmol/l for caffeine offspring, 2.3 +/- 0.2 mmol/l for caffeine with sucrose, 3.8 +/- 0.3 mmol/l for sucrose and 4.1 +/- 0.3 mmol/l for control offspring, mean +/- SEM). In contrast, offspring of sucrose-supplemented (with or without caffeine) dams showed increased sensitivity of the proinsulin biosynthetic process to glucose, whereas offspring of dams ingesting caffeine alone showed no significant enhancement of the biosynthetic process compared with control offspring. Thus enhanced sensitivity of the insulin secretory process to glucose without a change in the sensitivity of the biosynthetic process in the offspring of the caffeine ingesting (non-sucrose supplemented) dams could explain the progressive depletion of pancreatic insulin stores and eventual hypoinsulinaemia seen in this group.

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

    SciTech Connect

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

    1988-07-01

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

  13. 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

  14. Liver Function Tests

    MedlinePlus

    ... Your Liver > Liver Disease Information > Liver Function Tests Liver Function Tests Explore this section to learn more ... including a description and diagnosis. Why is the liver important? The liver is the second largest organ ...

  15. Mitochondrial function and malfunction in the pathophysiology of pancreatitis.

    PubMed

    Gerasimenko, Oleg V; Gerasimenko, Julia V

    2012-07-01

    As a primary energy producer, mitochondria play a fundamental role in pancreatic exocrine physiology and pathology. The most frequent aetiology of acute pancreatitis is either gallstones or heavy alcohol consumption. Repeated episodes of acute pancreatitis can result in the development of chronic pancreatitis and increase the lifetime risk of pancreatic cancer 100-fold. Pancreatic cancer is one of the most common causes of cancer mortality with only about 3-4 % of patients surviving beyond 5 years. It has been shown that acute pancreatitis involves Ca²⁺ overload and overproduction of reactive oxygen species in pancreatic acinar cells. Both factors significantly affect mitochondria and lead to cell death. The pathogenesis of inflammation in acute and chronic pancreatitis is tightly linked to the induction of necrosis and apoptosis. There is currently no specific therapy for pancreatitis, but recent findings of an endogenous protective mechanism against Ca²⁺ overload--and particularly the potential to boost this protection--bring hope of new therapeutic approaches.

  16. Selective ex-vivo photothermal ablation of human pancreatic cancer with albumin functionalized multiwalled carbon nanotubes

    PubMed Central

    Mocan, Lucian; Tabaran, Flaviu A; Mocan, Teodora; Bele, Constantin; Orza, Anamaria Ioana; Lucan, Ciprian; Stiufiuc, Rares; Manaila, Ioana; Iulia, Ferencz; Dana, Iancu; Zaharie, Florin; Osian, Gelu; Vlad, Liviu; Iancu, Cornel

    2011-01-01

    The process of laser-mediated ablation of cancer cells marked with biofunctionalized carbon nanotubes is frequently called “nanophotothermolysis”. We herein present a method of selective nanophotothermolisys of pancreatic cancer (PC) using multiwalled carbon nanotubes (MWCNTs) functionalized with human serum albumin (HSA). With the purpose of testing the therapeutic value of these nanobioconjugates, we have developed an ex-vivo experimental platform. Surgically resected specimens from patients with PC were preserved in a cold medium and kept alive via intra-arterial perfusion. Additionally, the HSA-MWCNTs have been intra-arterially administered in the greater pancreatic artery under ultrasound guidance. Confocal and transmission electron microscopy combined with immunohistochemical staining have confirmed the selective accumulation of HSA-MWCNTs inside the human PC tissue. The external laser irradiation of the specimen has significantly produced extensive necrosis of the malign tissue after the intra-arterial administration of HSA-MWCNTs, without any harmful effects on the surrounding healthy parenchyma. We have obtained a selective photothermal ablation of the malign tissue based on the selective internalization of MWCNTs with HSA cargo inside the pancreatic adenocarcinoma after the ex-vivo intra-arterial perfusion. PMID:21720504

  17. Effect of fluoroquinolones on mitochondrial function in pancreatic beta cells.

    PubMed

    Ghaly, Hany; Jörns, Anne; Rustenbeck, Ingo

    2014-02-14

    Hyper- and hypoglycaemias are known side effects of fluoroquinolone antibiotics, resulting in a number of fatalities. Fluoroquinolone-induced hypoglycaemias are due to stimulated insulin release by the inhibition of the KATP channel activity of the beta cell. Recently, it was found that fluoroquinolones were much less effective on metabolically intact beta cells than on open cell preparations. Thus the intracellular effects of gatifloxacin, moxifloxacin and ciprofloxacin were investigated by measuring NAD(P)H- and FAD-autofluorescence, the mitochondrial membrane potential, and the adenine nucleotide content of isolated pancreatic islets and beta cells. 100 μM of moxifloxacin abolished the NAD(P)H increase elicited by 20mM glucose, while gatifloxacin diminished it and ciprofloxacin had no significant effect. This pattern was also seen with islets from SUR1 Ko mice, which have no functional KATP channels. Moxifloxacin also diminished the glucose-induced decrease of FAD-fluorescence, which reflects the intramitochondrial production of reducing equivalents. Moxifloxacin, but not ciprofloxacin or gatifloxacin significantly reduced the effect of 20mM glucose on the ATP/ADP ratio. The mitochondrial hyperpolarization caused by 20mM glucose was partially antagonized by moxifloxacin, but not by ciprofloxacin or gatifloxacin. Ultrastructural analyses after 20 h tissue culture showed that all three compounds (at 10 and 100 μM) diminished the number of insulin secretory granules and that gatifloxacin and ciprofloxacin, but not moxifloxacin induced fission/fusion configurations of the beta cell mitochondria. In conclusion, fluoroquinolones affect the function of the mitochondria in pancreatic beta cells which may diminish the insulinotropic effect of KATP channel closure and contribute to the hyperglycaemic episodes.

  18. 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.

  19. Comprehensive analysis of cellular galectin-3 reveals no consistent oncogenic function in pancreatic cancer cells.

    PubMed

    Hann, Alexander; Gruner, Anja; Chen, Ying; Gress, Thomas M; Buchholz, Malte

    2011-01-01

    Galectin-3 (Gal-3), a 31 kDa member of the family of beta-galactoside-binding proteins, has been implicated in the progression of different human cancers. However, the proposed roles differ widely, ranging from tumor-promoting cellular functions and negative impact on patient prognosis to tumor-suppressive properties and positive prognostic impact. We and others have previously identified Gal-3 as overexpressed in pancreatic cancer as compared to chronic pancreatitis and normal pancreatic tissue. The purpose of this study was thus the comprehensive analysis of putative cellular functions of Gal-3 by transient as well as stable silencing or overexpression of Gal-3 in a panel of 6 well-established pancreatic cancer cell lines. Our results confirm that galectin-3 is upregulated at the mRNA level in pancreatic cancer and strongly expressed in the majority of pancreatic cancer cell lines. In individual cell lines, transient knockdown of Gal-3 expression resulted in moderate inhibitory effects on proliferation, migration or anchorage-independent growth of the cells, but these effects were not consistent across the spectrum of analyzed cell lines. Moreover, functional effects of the modulation of Gal-3 expression were not observed in stable knockdown or overexpression approaches in vitro and did not alter the growth characteristics of nude mouse xenograft tumors in vivo. Our data thus do not support a direct functional role of Gal-3 in the malignant transformation of pancreatic epithelial cells, although paracrine or systemic effects of Gal-3 expression are not excluded.

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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

  5. A novel fluorescence imaging approach for comparative measurements of pancreatic islet function in vitro.

    PubMed

    Corbin, Kathryn L; Hall, Thomas E; Haile, Ruth; Nunemaker, Craig S

    2011-01-01

    Pancreatic islet dysfunction is a key element in the development of type 2 diabetes. Determining possible early warning signs of dysfunction is thus important to determining the underlying causes of diabetes. We describe an improved fluorescent imaging approach to detect potential islet dysfunction. Using Cell Tracker Red (CTR, a mildly thiol-reactive fluorescent probe) to positively label particular islets, we measured intracellular free calcium with fura-2 AM in both CTR-labeled and unlabeled sets of pancreatic islets simultaneously in vitro. This approach enhances sensitivity by controlling for differences in background fluorescence, temperature, and perifusion dynamics. We confirmed that 200 nM CTR produced no spectral overlap with fura-2 and no significant physiological effects in selective tests of islet function. To demonstrate the utility of dual-labeling, we compared untreated islets with islets pretreated with low-dose pro-inflammatory cytokines (IL-6 + IL-1B) to induce mild dysfunction. We alternated CTR-labeling between control and test islets and identified consistent reductions in the amplitude and trajectory of glucose-stimulated calcium responses (GSCa) among cytokine-treated islets that were independent of labeling. Observations were verified using a MATLAB program specifically designed to identify key features in the GSCa. Our findings thus demonstrate the utility of CTR-labeling in identifying islet dysfunction and propose that this technique can be adapted for other cells and tissues.

  6. Pulmonary function testing.

    PubMed

    Ruppel, Gregg L; Enright, Paul L

    2012-01-01

    Pulmonary function testing is often considered the basis for diagnosis in many categories of pulmonary disease. Although most of the testing methodologies are well established and widely employed, there are still many questions regarding how tests should be performed, how to ensure that reliable data are produced, what reference values and rules should be used, and how pulmonary function tests (PFTs) should be interpreted to best support clinical decision making. This conference was organized around a set of questions aimed at many of these issues. Each presenter was asked to address a specific topic regarding what tests should be done, how those test should be performed to answer a particular clinical question, and to relate test results to an accurate diagnosis and appropriate treatment of the patient. These topics included testing of adults and children, with concentration on important disease entities such as COPD, asthma, and unexplained dyspnea. Special emphasis was given to discussing reference values, lower limits of normal, interpretive strategies to optimize disease classification, and those factors directly affecting data quality. Established techniques for spirometry, lung volumes, diffusing capacity, exercise testing, and bronchial challenges were compared and contrasted with new technologies, and with technologies that might be part of pulmonary function laboratories in the near future.

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

    PubMed

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

    2015-04-01

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

  8. Role of endoscopic ultrasonography in the diagnosis of acute and chronic pancreatitis.

    PubMed

    Stevens, Tyler

    2013-10-01

    Endoscopic ultrasonography (EUS) can be a useful tool for detecting underlying causes of acute pancreatitis and establishing the severity of fibrosis in chronic pancreatitis. Ancillary techniques include fine needle aspiration and core biopsy, bile collection for crystal analysis, pancreatic function testing, and celiac plexus block. This review focuses on the role of EUS in the diagnosis of acute and chronic pancreatitis.

  9. Platelet Function Tests.

    PubMed

    Lordkipanidzé, Marie

    2016-04-01

    Traditionally developed for diagnosis of bleeding disorders, platelet function assays have become increasingly used in basic research on platelet physiology, in phenotype-genotype associations in bleeding disorders, in drug development as surrogate endpoints of efficacy of new antiplatelet therapy, and to an extent, in the monitoring of antiplatelet therapy in clinical practice to predict thrombotic and bleeding risk. A multiplicity of platelet function assays is available to measure the level of platelet activity in various settings. These include assays that are restricted to a specialized laboratory as well as point-of-care instruments meant to investigate platelet function at patient bedside. Unlike tests that determine a defined quantity or measurement of a clinical biomarker (e.g., cholesterol or blood pressure), platelet function testing assesses the dynamics of living cells, which immediately presents a series of unique problems to any laboratory or clinic. This article presents currently used platelet function assays and discusses important variables to take into account when performing these assays, including preanalytical issues and difficulties in interpreting platelet function test results.

  10. Pancreatic adenocarcinoma up-regulated factor (PAUF) enhances the accumulation and functional activity of myeloid-derived suppressor cells (MDSCs) in pancreatic cancer.

    PubMed

    Song, Jinhoi; Lee, Jaemin; Kim, Jinsil; Jo, Seongyea; Kim, Yeon Jeong; Baek, Ji Eun; Kwon, Eun-Soo; Lee, Kwang-Pyo; Yang, Siyoung; Kwon, Ki-Sun; Kim, Dong-Uk; Kang, Tae Heung; Park, Yun-Yong; Chang, Suhwan; Cho, Hee Jun; Kim, Song Cheol; Koh, Sang Seok; Kim, Seokho

    2016-08-09

    Pancreatic cancer is characterized by an immunosuppressive tumor microenvironment (TME) with a profound immune infiltrate populated by a significant number of myeloid-derived suppressor cells (MDSCs). MDSCs have been increasingly recognized for their role in immune evasion and cancer progression as well as their potential as a target for immunotherapy. However, not much is known about the mechanisms regulating their behavior and function in the pancreatic TME. Here we report that pancreatic adenocarcinoma up-regulated factor (PAUF), a soluble protein involved in pancreatic tumorigenesis and metastasis, plays a role as an enhancer of tumor-infiltrating MDSC and its functional activity. We show that PAUF enhanced the accumulation of MDSCs in the spleen and tumor tissues of PAUF-overexpressing tumor cell-injected mice. In addition, PAUF was found to enhance the immunosuppressive function of MDSCs via the TLR4-mediated signaling pathway, which was demonstrated by PAUF-induced increased levels of arginase, nitric oxide (NO), and reactive oxygen species (ROS). The role of PAUF in modulating the functional properties of MDSCs was further demonstrated by the use of a PAUF-neutralizing antibody that caused a decreased number of tumor-infiltrating MDSCs and reduced MDSC immunosuppressive activity. The observations made in mice were confirmed in human pancreatic cancer patient-derived MDSCs, supporting the clinical relevance of our findings. Collectively, we conclude that the PAUF is a powerful and multifunctional promoter of tumor growth through increase and functional activation of MDSCs, suggesting therapeutic potential for targeting PAUF in pancreatic cancers.

  11. Imaging tests for accurate diagnosis of acute biliary pancreatitis.

    PubMed

    Şurlin, Valeriu; Săftoiu, Adrian; Dumitrescu, Daniela

    2014-11-28

    Gallstones represent the most frequent aetiology of acute pancreatitis in many statistics all over the world, estimated between 40%-60%. Accurate diagnosis of acute biliary pancreatitis (ABP) is of outmost importance because clearance of lithiasis [gallbladder and common bile duct (CBD)] rules out recurrences. Confirmation of biliary lithiasis is done by imaging. The sensitivity of the ultrasonography (US) in the detection of gallstones is over 95% in uncomplicated cases, but in ABP, sensitivity for gallstone detection is lower, being less than 80% due to the ileus and bowel distension. Sensitivity of transabdominal ultrasonography (TUS) for choledocolithiasis varies between 50%-80%, but the specificity is high, reaching 95%. Diameter of the bile duct may be orientative for diagnosis. Endoscopic ultrasonography (EUS) seems to be a more effective tool to diagnose ABP rather than endoscopic retrograde cholangiopancreatography (ERCP), which should be performed only for therapeutic purposes. As the sensitivity and specificity of computerized tomography are lower as compared to state-of-the-art magnetic resonance cholangiopancreatography (MRCP) or EUS, especially for small stones and small diameter of CBD, the later techniques are nowadays preferred for the evaluation of ABP patients. ERCP has the highest accuracy for the diagnosis of choledocholithiasis and is used as a reference standard in many studies, especially after sphincterotomy and balloon extraction of CBD stones. Laparoscopic ultrasonography is a useful tool for the intraoperative diagnosis of choledocholithiasis. Routine exploration of the CBD in cases of patients scheduled for cholecystectomy after an attack of ABP was not proven useful. A significant rate of the so-called idiopathic pancreatitis is actually caused by microlithiasis and/or biliary sludge. In conclusion, the general algorithm for CBD stone detection starts with anamnesis, serum biochemistry and then TUS, followed by EUS or MRCP. In the end

  12. Context-dependent function of the deubiquitinating enzyme USP9X in pancreatic ductal adenocarcinoma.

    PubMed

    Cox, Jesse L; Wilder, Phillip J; Wuebben, Erin L; Ouellette, Michel M; Hollingsworth, Michael A; Rizzino, Angie

    2014-08-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadly malignancies. Recently, the deubiquitinating protease USP9X has been shown to behave as an oncogene in a number of neoplasms, including those of breast, brain, colon, esophagus and lung, as well as KRAS wild-type PDAC. However, other studies suggest that USP9X may function as a tumor-suppressor in a murine PDAC model when USP9X expression is depleted during early pancreatic development. To address the conflicting findings surrounding the role of USP9X in PDAC, we examined the effects of knocking down USP9X in five human PDAC cell lines (BxPC3, Capan1, CD18, Hs766T, and S2-013). We demonstrate that knocking down USP9X in each of the PDAC cell lines reduces their anchorage-dependent growth. Using an inducible shRNA system to knock down USP9X in both BxPC3 and Capan1 cells, we also determined that USP9X is necessary for the anchorage-independent growth. In addition, knockdown of USP9X alters the cell cycle profile of BxPC3 cells and increases their invasive capacity. Finally, we show that an inhibitor of deubiquitinating proteases, WP1130, induces significant cytotoxicity in each of the five PDAC cell lines tested. Overall, our work and the work of others indicate that the function and role of USP9X is highly context-dependent. Although USP9X may function as a tumor-suppressor during the establishment of PDAC, data presented here argue that USP9X promotes cell growth in advanced PDAC cells when PDAC is typically diagnosed. Hence, USP9X may be a promising therapeutic target for the treatment of advanced PDAC.

  13. Context-dependent function of the deubiquitinating enzyme USP9X in pancreatic ductal adenocarcinoma

    PubMed Central

    Cox, Jesse L; Wilder, Phillip J; Wuebben, Erin L; Ouellette, Michel M; Hollingsworth, Michael A; Rizzino, Angie

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadly malignancies. Recently, the deubiquitinating protease USP9X has been shown to behave as an oncogene in a number of neoplasms, including those of breast, brain, colon, esophagus and lung, as well as KRAS wild-type PDAC. However, other studies suggest that USP9X may function as a tumor-suppressor in a murine PDAC model when USP9X expression is depleted during early pancreatic development. To address the conflicting findings surrounding the role of USP9X in PDAC, we examined the effects of knocking down USP9X in five human PDAC cell lines (BxPC3, Capan1, CD18, Hs766T, and S2-013). We demonstrate that knocking down USP9X in each of the PDAC cell lines reduces their anchorage-dependent growth. Using an inducible shRNA system to knock down USP9X in both BxPC3 and Capan1 cells, we also determined that USP9X is necessary for the anchorage-independent growth. In addition, knockdown of USP9X alters the cell cycle profile of BxPC3 cells and increases their invasive capacity. Finally, we show that an inhibitor of deubiquitinating proteases, WP1130, induces significant cytotoxicity in each of the five PDAC cell lines tested. Overall, our work and the work of others indicate that the function and role of USP9X is highly context-dependent. Although USP9X may function as a tumor-suppressor during the establishment of PDAC, data presented here argue that USP9X promotes cell growth in advanced PDAC cells when PDAC is typically diagnosed. Hence, USP9X may be a promising therapeutic target for the treatment of advanced PDAC. PMID:24841553

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

    PubMed

    Navis, Adam; Bagnat, Michel

    2015-03-15

    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.

  15. 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

  16. [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.

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

    PubMed Central

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

    2016-01-01

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

  18. SGLT2 Deletion Improves Glucose Homeostasis and Preserves Pancreatic β-Cell Function

    PubMed Central

    Jurczak, Michael J.; Lee, Hui-Young; Birkenfeld, Andreas L.; Jornayvaz, Francois R.; Frederick, David W.; Pongratz, Rebecca L.; Zhao, Xiaoxian; Moeckel, Gilbert W.; Samuel, Varman T.; Whaley, Jean M.; Shulman, Gerald I.; Kibbey, Richard G.

    2011-01-01

    OBJECTIVE Inhibition of the Na+-glucose cotransporter type 2 (SGLT2) is currently being pursued as an insulin-independent treatment for diabetes; however, the behavioral and metabolic consequences of SGLT2 deletion are unknown. Here, we used a SGLT2 knockout mouse to investigate the effect of increased renal glucose excretion on glucose homeostasis, insulin sensitivity, and pancreatic β-cell function. RESEARCH DESIGN AND METHODS SGLT2 knockout mice were fed regular chow or a high-fat diet (HFD) for 4 weeks, or backcrossed onto the db/db background. The analysis used metabolic cages, glucose tolerance tests, euglycemic and hyperglycemic clamps, as well as isolated islet and perifusion studies. RESULTS SGLT2 deletion resulted in a threefold increase in urine output and a 500-fold increase in glucosuria, as well as compensatory increases in feeding, drinking, and activity. SGLT2 knockout mice were protected from HFD-induced hyperglycemia and glucose intolerance and had reduced plasma insulin concentrations compared with controls. On the db/db background, SGLT2 deletion prevented fasting hyperglycemia, and plasma insulin levels were also dramatically improved. Strikingly, prevention of hyperglycemia by SGLT2 knockout in db/db mice preserved pancreatic β-cell function in vivo, which was associated with a 60% increase in β-cell mass and reduced incidence of β-cell death. CONCLUSIONS Prevention of renal glucose reabsorption by SGLT2 deletion reduced HFD- and obesity-associated hyperglycemia, improved glucose intolerance, and increased glucose-stimulated insulin secretion in vivo. Taken together, these data support SGLT2 inhibition as a viable insulin-independent treatment of type 2 diabetes. PMID:21357472

  19. Functional characteristics of L1156F-CFTR associated with alcoholic chronic pancreatitis in Japanese.

    PubMed

    Kondo, Shiho; Fujiki, Kotoyo; Ko, Shigeru B H; Yamamoto, Akiko; Nakakuki, Miyuki; Ito, Yasutomo; Shcheynikov, Nikolay; Kitagawa, Motoji; Naruse, Satoru; Ishiguro, Hiroshi

    2015-08-15

    Although cystic fibrosis is rare in Japanese, measurement of sweat Cl(-) has suggested mild dysfunction of cystic fibrosis transmembrane conductance regulator (CFTR) in some patients with chronic pancreatitis. In the present study, we have investigated the association of CFTR variants and chronic pancreatitis in Japanese and the functional characteristics of a Japanese- and pancreatitis-specific CFTR variant, L1156F. Seventy patients with alcoholic chronic pancreatitis, 18 patients with idiopathic chronic pancreatitis, and 180 normal subjects participated. All exons and their boundaries and promoter region of the CFTR gene were sequenced. Human embryonic kidney-293 cells were transfected with three CFTR variants (M470V, L1156F, and M470V+L1156F), and the protein expression was examined. Xenopus laevis oocytes were injected with the CFTR variants, and bicarbonate (HCO3 (-)) transport activity was examined. CFPAC-1 cells were transfected with the CFTR variants and Cl(-)/HCO3 (-) exchange activity was examined. Six variants (E217G, I556V, M470V, L1156F, Q1352H, and R1453W) were identified in the coding region of the CFTR gene. Cystic fibrosis-causing mutations were not found. The allele frequencies of L1156F and Q1352H in alcoholic chronic pancreatitis (5.0 and 7.9%) were significantly (P < 0.01) higher than those in normal subjects (0.6 and 1.9%). L1156F was linked with a worldwide CFTR variant, M470V. Combination of M470V and L1156F significantly reduced CFTR expression to ∼60%, impaired CFTR-mediated HCO3 (-)/Cl(-) transport activity to 50-60%, and impaired CFTR-coupled Cl(-)/HCO3 (-) exchange activity to 20-30%. The data suggest that the Japanese-specific CFTR variant L1156F causes mild dysfunction of CFTR and increases the risk of alcoholic chronic pancreatitis in Japanese.

  20. 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

  1. Functional significance of macrophages in pancreatic cancer biology.

    PubMed

    Hu, Hai; Jiao, Feng; Han, Ting; Wang, Li-Wei

    2015-12-01

    Pancreatic ductal adenocarcinoma (PDA) is a lethal disease that is usually diagnosed at late stage with few effective therapies. Despite the rapid progress on the genomics and proteomics of the neoplastic cells, therapies that targeted the pancreatic cancer cells proved to be inefficient, which promoted the researchers to turn their attentions to the microenvironment. Currently, various studies had proposed the microenvironment to be a contributing factor for PDA and pervasive researches showed that macrophages within the malignancy correlate with the malignant phenotype of the disease and were reported to a new therapeutic target. Generally, the pro-tumoral effects of macrophages can be summarized as angiogenesis promotion, immunosuppression, matrix remodeling and so on. Hence, a comprehensive understanding of the biologic behaviors of macrophages and their critical role in PDA development may provide new directions for the managements of the lethal disease. In this review, we will summarize the recent advancements on macrophages as pivotal players in PDA biology and the current knowledge about anti-macrophages as a novel strategy against cancer, with the expectation that more efficient therapies will be developed in the near future.

  2. 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.

  3. VEGF-A: the inductive angiogenic factor for development, regeneration and function of pancreatic beta cells.

    PubMed

    Lui, Kathy O

    2014-01-01

    The heart is the first organ to form during development in vertebrates, and many organs start to develop adjacent to the cardiovascular system. Endothelial cells (ECs) form the inner cell lining of blood vessels and represent the major cell type that interacts with developing organs including the pancreas. ECs receive signals from the developing pancreas to grow and, at the same time, release signals to determine cell-fate specification, morphogenesis and function of the pancreas. In addition to promoting survival of pancreatic islets, in this review, we discuss the role of the vascular niche and angiogenic factors, particularly VEGFA, during pancreatic beta cell development, regeneration and pathophysiological progression of diabetes. Nevertheless, unraveling the molecular signals involved in pancreatic beta cell development and regeneration may shed light into novel drug development to treat diabetes.

  4. IL-17 functions through the novel REG3β-JAK2-STAT3 inflammatory pathway to promote the transition from chronic pancreatitis to pancreatic cancer

    PubMed Central

    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

    2015-01-01

    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 IL-17 pathway mediates this phenomenon and can be targeted with antibodies, but the downstream mechanisms by which IL-17 functions during this transition are currently unclear. In this study, we demonstrate that IL-17 induces the expression of REG3β, a well-known mediator of pancreatitis, during acinar-to-ductal metaplasia and in early 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 pathophysiological role for REG3β during pancreatitis and PDAC initiation. PMID:26404002

  5. 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).

  6. [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.

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

    PubMed

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

    2016-07-01

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

  8. 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

  9. Pancreatitis - children

    MedlinePlus

    ... an organ or bone marrow transplant Cystic fibrosis Crohn disease and other disorders when the body's immune system ... lab tests to check the release of pancreatic enzymes. These include tests to check the: Blood amylase ...

  10. Pancreatic adenocarcinoma up-regulated factor (PAUF) enhances the accumulation and functional activity of myeloid-derived suppressor cells (MDSCs) in pancreatic cancer

    PubMed Central

    Jo, Seongyea; Kim, Yeon Jeong; Baek, Ji Eun; Kwon, Eun-Soo; Lee, Kwang-Pyo; Yang, Siyoung; Kwon, Ki-Sun; Kim, Dong-Uk; Kang, Tae Heung; Park, Yun-Yong; Chang, Suhwan; Cho, Hee Jun; Kim, Song Cheol; Koh, Sang Seok; Kim, Seokho

    2016-01-01

    Pancreatic cancer is characterized by an immunosuppressive tumor microenvironment (TME) with a profound immune infiltrate populated by a significant number of myeloid-derived suppressor cells (MDSCs). MDSCs have been increasingly recognized for their role in immune evasion and cancer progression as well as their potential as a target for immunotherapy. However, not much is known about the mechanisms regulating their behavior and function in the pancreatic TME. Here we report that pancreatic adenocarcinoma up-regulated factor (PAUF), a soluble protein involved in pancreatic tumorigenesis and metastasis, plays a role as an enhancer of tumor-infiltrating MDSC and its functional activity. We show that PAUF enhanced the accumulation of MDSCs in the spleen and tumor tissues of PAUF-overexpressing tumor cell-injected mice. In addition, PAUF was found to enhance the immunosuppressive function of MDSCs via the TLR4-mediated signaling pathway, which was demonstrated by PAUF-induced increased levels of arginase, nitric oxide (NO), and reactive oxygen species (ROS). The role of PAUF in modulating the functional properties of MDSCs was further demonstrated by the use of a PAUF-neutralizing antibody that caused a decreased number of tumor-infiltrating MDSCs and reduced MDSC immunosuppressive activity. The observations made in mice were confirmed in human pancreatic cancer patient-derived MDSCs, supporting the clinical relevance of our findings. Collectively, we conclude that the PAUF is a powerful and multifunctional promoter of tumor growth through increase and functional activation of MDSCs, suggesting therapeutic potential for targeting PAUF in pancreatic cancers. PMID:27322081

  11. 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.

  12. [Effect of apparatus plasmapheresis on the bowel barrier and motility function in patients with acute necrotizing pancreatitis].

    PubMed

    Dronov, O I; Koval's'ka, I O; Uvarov, V Iu; Horlach, A I; Fedoruk, V I; Burmich, K S; Lykhodeĭ, K O; Shvets', Iu P

    2013-04-01

    Influence of therapeutic plasmapheresis on bowel barrier function and evacuation was investigated in 83 patients with severe acute necrotizing pancreatitis. Except standard therapy patient obtained therapeutic plasmapheresis using "Haemonetics" PCS 2 system. Complex treatment of patients with acute necrotizing pancreatitis and dynamic ileus using plasmapheresis increases contractive and propulsive function of stomach and duodenum and prolongs period of activity of these organs on 32%. Intestinal barrier function associates with restoration of bowel evacuation. Addition of plasmapheresis to standard therapy of necrotizing pancreatitis can be effective prevention of dynamic ileus.

  13. Zinc, pancreatic islet cell function and diabetes: new insights into an old story.

    PubMed

    Chimienti, Fabrice

    2013-06-01

    Zn is an essential trace element, involved in many different cellular processes. A relationship between Zn, pancreatic function and diabetes was suggested almost 70 years ago. To emphasise the importance of Zn in biology, the history of Zn research in the field of diabetes along with a general description of Zn transporter families will be reviewed. The paper will then focus on the effects of Zn on pancreatic β-cell function, including insulin synthesis and secretion, Zn signalling in the pancreatic islet, the redox functions of Zn and its target genes. The recent association of two 'Zn genes', i.e. metallothionein (MT) and Zn transporter 8 (SLC 30A8), with type 2 diabetes at the genetic level and with insulin secretion in clinical studies offers a potential new way to identify new drug targets to modulate Zn homeostasis directly in β-cells. The action of Zn for insulin action in its target organs, as Zn signalling in other pancreatic islet cells, will be addressed. Therapeutic Zn-insulin preparations and the influence of Zn and Zn transporters in type 1 diabetes will also be discussed. An extensive review of the literature on the clinical studies using Zn supplementation in the prevention and treatment of both types of diabetes, including complications of the disease, will evaluate the overall beneficial effects of Zn supplementation on blood glucose control, suggesting that Zn might be a candidate ion for diabetes prevention and therapy. Clearly, the story of the links between Zn, pancreatic islet cells and diabetes is only now unfolding, and we are presently only at the first chapter.

  14. 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)

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

    PubMed

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

    2012-01-01

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

  16. 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.

  17. 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

  18. Acute pancreatitis

    MedlinePlus

    ... mg/dL Injury to the pancreas from an accident Other causes include: After certain procedures used to ... pressure Rapid heart rate Rapid breathing (respiratory) rate Lab tests that show the release of pancreatic enzymes ...

  19. In vivo functional dissection of a context-dependent role for Hif1α in pancreatic tumorigenesis

    PubMed Central

    Cheng, T; Jian, Z; Li, K; Raulefs, S; Regel, I; Shen, S; Zou, X; Ruland, J; Ceyhan, G O; Friess, H; Michalski, C W; Kleeff, J; Kong, B

    2016-01-01

    Hypoxia-inducible factor 1α (Hif1α) is a key regulator of cellular adaptation and survival under hypoxic conditions. In pancreatic ductal adenocarcinoma (PDAC), it has been recently shown that genetic ablation of Hif1α accelerates tumour development by promoting tumour-supportive inflammation in mice, questioning its role as the key downstream target of many oncogenic signals of PDAC. Likely, Hif1α has a context-dependent role in pancreatic tumorigenesis. To further analyse this, murine PDAC cell lines with reduced Hif1α expression were generated using shRNA transfection. Cells were transplanted into wild-type mice through orthotopic or portal vein injection in order to test the in vivo function of Hif1α in two major tumour-associated biological scenarios: primary tumour growth and remote colonization/metastasis. Although Hif1α protects PDAC cells from stress-induced cell deaths in both scenarios—in line with the general function Hif1α—its depletion leads to different oncogenic consequences. Hif1α depletion results in rapid tumour growth with marked hypoxia-induced cell death, which potentially leads to a persistent tumour-sustaining inflammatory response. However, it simultaneously reduces tumour colonization and hepatic metastases by increasing the susceptibility to anoikis induced by anchorage-independent conditions. Taken together, the role of Hif1α in pancreatic tumorigenesis is context-dependent. Clinical trials of Hif1α inhibitors need to take this into account, targeting the appropriate scenario, for example palliative vs adjuvant therapy. PMID:27941931

  20. Platelet Function Tests

    MedlinePlus

    PLEASE NOTE: Your web browser does not have JavaScript enabled. Unless you enable Javascript , your ability to navigate and access the features of this website will be limited. ... Proceeds from website advertising help sustain Lab Tests Online. AACC is a not-for-profit organization and does not endorse non-AACC products and services. Advertising & Sponsorship: ...

  1. The Functions of Testing.

    ERIC Educational Resources Information Center

    Tumin, Melvin M.

    1981-01-01

    Admissions testing and its consequences are looked upon as a reflection of the current debate occurring in Western capitalist democracies concerning the optimization of freedom, fairness, and wealth. In dealing with the competition and conflict of values and interests, there can be no factual but political resolution. (Author/AL)

  2. Assessment of pancreatic β-cell function: review of methods and clinical applications.

    PubMed

    Cersosimo, Eugenio; Solis-Herrera, Carolina; Trautmann, Michael E; Malloy, Jaret; Triplitt, Curtis L

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is characterized by a progressive failure of pancreatic β-cell function (BCF) with insulin resistance. Once insulin over-secretion can no longer compensate for the degree of insulin resistance, hyperglycemia becomes clinically significant and deterioration of residual β-cell reserve accelerates. This pathophysiology has important therapeutic implications. Ideally, therapy should address the underlying pathology and should be started early along the spectrum of decreasing glucose tolerance in order to prevent or slow β-cell failure and reverse insulin resistance. The development of an optimal treatment strategy for each patient requires accurate diagnostic tools for evaluating the underlying state of glucose tolerance. This review focuses on the most widely used methods for measuring BCF within the context of insulin resistance and includes examples of their use in prediabetes and T2DM, with an emphasis on the most recent therapeutic options (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists). Methods of BCF measurement include the homeostasis model assessment (HOMA); oral glucose tolerance tests, intravenous glucose tolerance tests (IVGTT), and meal tolerance tests; and the hyperglycemic clamp procedure. To provide a meaningful evaluation of BCF, it is necessary to interpret all observations within the context of insulin resistance. Therefore, this review also discusses methods utilized to quantitate insulin-dependent glucose metabolism, such as the IVGTT and the euglycemic-hyperinsulinemic clamp procedures. In addition, an example is presented of a mathematical modeling approach that can use data from BCF measurements to develop a better understanding of BCF behavior and the overall status of glucose tolerance.

  3. Assessment of Pancreatic β-Cell Function: Review of Methods and Clinical Applications

    PubMed Central

    Cersosimo, Eugenio; Solis-Herrera, Carolina; Trautmann, Michael E.; Malloy, Jaret; Triplitt, Curtis L.

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is characterized by a progressive failure of pancreatic β-cell function (BCF) with insulin resistance. Once insulin over-secretion can no longer compensate for the degree of insulin resistance, hyperglycemia becomes clinically significant and deterioration of residual β-cell reserve accelerates. This pathophysiology has important therapeutic implications. Ideally, therapy should address the underlying pathology and should be started early along the spectrum of decreasing glucose tolerance in order to prevent or slow β-cell failure and reverse insulin resistance. The development of an optimal treatment strategy for each patient requires accurate diagnostic tools for evaluating the underlying state of glucose tolerance. This review focuses on the most widely used methods for measuring BCF within the context of insulin resistance and includes examples of their use in prediabetes and T2DM, with an emphasis on the most recent therapeutic options (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists). Methods of BCF measurement include the homeostasis model assessment (HOMA); oral glucose tolerance tests, intravenous glucose tolerance tests (IVGTT), and meal tolerance tests; and the hyperglycemic clamp procedure. To provide a meaningful evaluation of BCF, it is necessary to interpret all observations within the context of insulin resistance. Therefore, this review also discusses methods utilized to quantitate insulin-dependent glucose metabolism, such as the IVGTT and the euglycemic-hyperinsulinemic clamp procedures. In addition, an example is presented of a mathematical modeling approach that can use data from BCF measurements to develop a better understanding of BCF behavior and the overall status of glucose tolerance. PMID:24524730

  4. Serum CA19-9 Level Associated with Metabolic Control and Pancreatic Beta Cell Function in Diabetic Patients

    PubMed Central

    Yu, Haoyong; Li, Ruixia; Zhang, Lei; Chen, Haibing; Bao, Yuqian; Jia, Weiping

    2012-01-01

    CA19-9 is a tumor-associated antigen. It is also a marker of pancreatic tissue damage that might be caused by diabetes. Long-term poor glycemic control may lead to pancreatic beta cell dysfunction which is reflected by elevated serum CA19-9 level. Intracellular cholesterol accumulation leads to islet dysfunction and impaired insulin secretion which provide a new lipotoxic model. This study firstly found total cholesterol was one of the independent contributors to CA19-9. Elevated serum CA19-9 level in diabetic patients may indicate further investigations of glycemic control, pancreatic beta cell function, and total cholesterol level. PMID:22778715

  5. 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

  6. 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.

  7. Soluble complement receptor 1 preserves endothelial barrier function and microcirculation in postischemic pancreatitis in the rat.

    PubMed

    von Dobschuetz, E; Bleiziffer, O; Pahernik, S; Dellian, M; Hoffmann, T; Messmer, K

    2004-05-01

    Components of the activated complement cascade are considered to play a pivotal role in ischemia-reperfusion-induced organ injury. With the use of intravital epifluorescence microscopy, we investigated the effect of complement inhibition by the recombinant soluble complement receptor 1 (sCR1; TP10) on the effect of macromolecular microvascular permeability, functional capillary perfusion, and leukocyte endothelium interaction in postischemic pancreatitis. Anaesthetized Sprague-Dawley rats were subjected to 60 min of normothermic pancreatic ischemia induced by microclipping of the blood-supplying arteries of the organ. Rats who received sCR1 (15 mg/kg body wt iv; n = 7) during reperfusion showed a significant reduction of permeability (1.77 +/- 1.34 x 10(-8) cm/s; n = 7) of tetramethylrhodamine isothiocyanate-labeled albumin injected 90 min after the onset of reperfusion compared with vehicle-treated animals (6.95 +/- 1.56 x 10(-8) cm/s; n = 7). At 120 min after the onset of reperfusion, the length of red blood cell-perfused capillaries (functional capillary density) was significantly improved (from 279 +/- 15.7 to 330 +/- 3.7 cm(-1); n = 7) and the number of leukocytes adherent to postcapillary venules was significantly reduced (from 314 +/- 87 to 163 +/- 71 mm(-2); n = 7) by sCR1 compared with vehicle treatment. Complement inhibition by sCR1 effectively ameliorates pancreatic ischemia-reperfusion-induced microcirculatory disturbances and might be considered for treatment of postischemic pancreatitis.

  8. Pancreatic Exocrine Insufficiency in Pancreatic Cancer.

    PubMed

    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J-Matthias

    2017-02-23

    Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  9. 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

  10. 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

  11. Chronic pancreatitis.

    PubMed

    Lindley, Keith J

    2006-10-01

    Chronic pancreatitis (CP) is characterised by pancreatic inflammation and fibrosis leading eventually to destruction of pancreatic parenchyma and loss of exocrine and endocrine function. A model of interactions between environmental triggers of pancreatic inflammation and disease susceptibility or modifying genes (including PRSS1, SPINK1 and CFTR) provides a framework within which to understand disease pathogenesis. Early in the disease, when fibrosis is mild and pancreatic damage limited, it is difficult to distinguish CP from recurrent acute pancreatitis (RAP) although it is likely these represent opposite ends of a spectrum of disease with a common aetiology in which CP represents either a later disease stage or disease in individuals predisposed to generate a chronic fibrogenic inflammatory response. Pain is a dominant feature resulting in part from neuroimmune interactions within the pancreas. Diagnosis at an early stage of disease is challenging, though in later stages is dependent upon the demonstration of pancreatic fibrosis and duct ectasia using one or more imaging modalities including transabdominal and endoscopic ultrasound, CT and MRCP or ERCP. Current treatments are largely supportive and reactive. The challenge for pediatricians is to achieve diagnosis at an early stage of the disease and to develop treatments that can alter its natural history.

  12. Antioxidant effect of angiotensin (1-7) in the protection of pancreatic β cell function

    PubMed Central

    Zhang, Fen; Liu, Chang; Wang, Lei; Cao, Xi; Wang, Ying Ying; Yang, Jin Kui

    2016-01-01

    It is well known that the local renin-angiotensin system (RAS) is activated in the diabetic state, which results in an increase in the level of oxidative stress injury to pancreatic β cells. The angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7) [Ang (1-7)]/Mas axis is a negative regulator of the classical renin-angiotensin system. In order to investigate the antioxidant effect of Ang (1-7) on pancreatic β cells, INS-1 cells were cultured and oxidative stress was induced by treatment with H2O2. Glucose-stimulated insulin secretion (GSIS), the generation of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and glucose-stimulated calcium (GSCa) responses in β cells were determined following treatment with Ang (1-7). It was observed that H2O2 significantly impaired the insulin secreting function, increased the production of ROS, and also decreased the levels of GSCa and MMP. Pre-treatment with Ang (1-7) alleviated these effects and treatment with A779 [antagonist of Ang (1-7)] prevented the effects of Ang (1-7). Based on these findings, it was concluded that Ang (1-7) can protect pancreatic β cells from oxidative injury and such protection can be blocked by its antagonist A779. PMID:27430410

  13. Hereditary Pancreatitis

    MedlinePlus

    ... meals throughout the day that are high in carbohydrates and low in protein and fat. Pancreatic enzymes ... the Pancreas NPF Centers Pancreatitis Centers Pancreatitis Center Application Pancreatic Cancer Centers Diagnosis of Pancreatic Cancer Pancreas ...

  14. Chronic pancreatitis in dogs.

    PubMed

    Watson, Penny

    2012-08-01

    Chronic pancreatitis used to be considered uncommon in dogs, but recent pathological and clinical studies have confirmed that it is in fact a common and clinically significant disease. Clinical signs can vary from low-grade recurrent gastrointestinal signs to acute exacerbations that are indistinguishable from classical acute pancreatitis. Chronic pancreatitis is a significant cause of chronic pain in dogs, which must not be underestimated. It also results in progressive impairment of endocrine and exocrine function and the eventual development of diabetes mellitus or exocrine pancreatic insufficiency or both in some affected dogs at end stage. The etiology is unknown in most cases. Chronic pancreatitis shows an increased prevalence in certain breeds, and recent work in English Cocker Spaniels suggests it is part of a polysystemic immune-mediated disease in this breed. The histological and clinical appearance is different in different breeds, suggesting that etiologies may also be different. Diagnosis is challenging because the sensitivities of the available noninvasive tests are relatively low. However, with an increased index of suspicion, clinicians will recognize more cases that will allow them to institute supportive treatment to improve the quality of life of the patient.

  15. A new scaffold containing small intestinal submucosa and mesenchymal stem cells improves pancreatic islet function and survival in vitro and in vivo

    PubMed Central

    Wang, Dan; Ding, Xiaoming; Xue, Wujun; Zheng, Jin; Tian, Xiaohui; Li, Yang; Wang, Xiaohong; Song, Huanjin; Liu, Hua; Luo, Xiaohui

    2017-01-01

    It is unknown whether a scaffold containing both small intestinal submucosa (SIS) and mesenchymal stem cells (MSCs) for transplantation may improve pancreatic islet function and survival. In this study, we examined the effects of a SIS-MSC scaffold on islet function and survival in vitro and in vivo. MSCs and pancreatic islets were isolated from Sprague-Dawley rats, and SIS was isolated from Bamei pigs. The islets were apportioned among 3 experimental groups as follows: SIS-islets, SIS-MSC-islets and control-islets. In vitro, islet function was measured by a glucose-stimulated insulin secretion test; cytokines in cultured supernatants were assessed by enzyme-linked immunosorbent assay; and gene expression was analyzed by reverse transcription-quantitative PCR. In vivo, islet transplantation was performed in rats, and graft function and survival were monitored by measuring the blood glucose levels. In vitro, the SIS-MSC scaffold was associated with improved islet viability and enhanced insulin secretion compared with the controls, as well as with the increased the expression of insulin 1 (Ins1), pancreatic and duodenal homeobox 1 (Pdx1), platelet endothelial cell adhesion molecule 1 [Pecam1; also known as cluster of differentiation 31 (CD31)] and vascular endothelial growth factor A (Vegfa) in the islets, increased growth factor secretion, and decreased tumor necrosis factor (TNF) secretion. In vivo, the SIS-MSC scaffold was associated with improved islet function and graft survival compared with the SIS and control groups. On the whole, our findings demonstrate that the SIS-MSC scaffold significantly improved pancreatic islet function and survival in vitro and in vivo. This improvement may be associated with the upregulation of insulin expression, the improvement of islet microcirculation and the secretion of cytokines. PMID:27909715

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

    PubMed

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

    1998-05-01

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

  17. Therapeutic Approaches for Preserving or Restoring Pancreatic β-Cell Function and Mass

    PubMed Central

    Jung, Kyong Yeun; Kim, Kyoung Min

    2014-01-01

    The goal for the treatment of patients with diabetes has today shifted from merely reducing glucose concentrations to preventing the natural decline in β-cell function and delay the progression of disease. Pancreatic β-cell dysfunction and decreased β-cell mass are crucial in the development of diabetes. The β-cell defects are the main pathogenesis in patients with type 1 diabetes and are associated with type 2 diabetes as the disease progresses. Recent studies suggest that human pancreatic β-cells have a capacity for increased proliferation according to increased demands for insulin. In humans, β-cell mass has been shown to increase in patients showing insulin-resistance states such as obesity or in pregnancy. This capacity might be useful for identifying new therapeutic strategies to reestablish a functional β-cell mass. In this context, therapeutic approaches designed to increase β-cell mass might prove a significant way to manage diabetes and prevent its progression. This review describes the various β-cell defects that appear in patients with diabetes and outline the mechanisms of β-cell failure. We also review common methods for assessing β-cell function and mass and methodological limitations in vivo. Finally, we discuss the current therapeutic approaches to improve β-cell function and increase β-cell mass. PMID:25541605

  18. Taurine's effects on the neuroendocrine functions of pancreatic β cells.

    PubMed

    Cuttitta, Christina M; Guariglia, Sara R; Idrissi, Abdeslem El; L'amoreaux, William J

    2013-01-01

    Taurine plays significant physiological roles, including those involved in neurotransmission. Taurine is a potent γ-aminobutyric acid (GABA) agonist and alters cellular events via GABA(A) receptors. Alternately, taurine is transported into cells via the high affinity taurine transporter (TauT), where it may also play a regulatory role. We have previously demonstrated that treatment of Hit-T15 cells with 1 mM taurine for 24 h significantly decreases insulin and GABA levels. We have also demonstrated that chronic in vivo administration of taurine results in an up-regulation of glutamic acid decarboxylase (GAD), the key enzyme in GABA synthesis. Here, we wished to test if administration of 1 mM taurine for 24 h may increase release of another β cell neurotransmitter somatostatin (SST) and also directly impact up-regulation of GAD synthesis. Treatment with taurine did not significantly alter levels of SST (p > 0.05) or GAD67 (p > 0.05). This suggests that taurine does not directly affect SST release, nor does it directly affect GAD synthesis. Taken together with our observation that taurine does promote GABA release via large dense-core vesicles, the data suggest that taurine may alter membrane potential, which in turn would affect calcium flux. We show here that 1 mM taurine does not alter intracellular Ca(2+) concentrations from 20 to 80 s post treatment (p > 0.05), but does increase Ca(2+) flux between 80 and 200 s post-treatment (p < 0.005). This suggests that taurine may induce a biphasic response in β cells. The initial response of taurine via GABA(A) receptors hyperpolarizes β cell and sequesters Ca(2+). Subsequently, taurine may affect Ca(2+) flux in long term via interaction with K(ATP) channels.

  19. Impaired synthesis of stromal components in response to Minnelide improves vascular function, drug delivery and survival in pancreatic cancer

    PubMed Central

    Banerjee, Sulagna; Modi, Shrey; McGinn, Olivia; Zhao, Xianda; Dudeja, Vikas; Ramakrishnan, Sundaram; Saluja, Ashok K

    2015-01-01

    Purpose Pancreatic cancer stromal microenvironment is considered to be the major reason for failure of conventional and targeted therapy for this disease. The desmoplastic stroma, comprising mainly of collagen and glycosaminoglycans like hyaluronan (HA), is responsible for compression of vasculature in the tumor resulting in impaired drug delivery and poor prognosis. Minnelide, a water-soluble pro-drug of triptolide currently in Phase I clinical trial, has been very effective in multiple animal models of pancreatic cancer. However, whether Minnelide will have efficacious delivery into the tumor in spite of the desmoplastic stroma, has not been evaluated before. Experiment design Patient tumor derived xenografts (PDX) and spontaneous pancreatic cancer mice were treated with 0.42 mg/kg and 0.21 mg/kg body weight for 30 days. Stromal components were determined by IHC and ELISA based assays. Vascular functionality and drug delivery to the tumor were assessed following treatment with Minnelide. Result Our current study shows that treatment with Minnelide resulted in reduction of ECM components like hyaluronan (HA) and collagen in the pancreatic cancer stroma of both the spontaneous KPC mice as well as in patient tumor xenografts. Further, treatment with Minnelide improved functional vasculature in the tumors resulting in 4- times more functional vessels in the treated animals compared to untreated animals. Consistent with this observation, Minnelide also resulted in increased drug delivery into the tumor compared to untreated animals. Along with this, Minnelide also decreased viability of the stromal cells along with the tumor cells in pancreatic adenocarcinoma. Conclusion In conclusion, these results are extremely promising as they indicate that Minnelide, along with having anti-cancer effects is also able to deplete stroma in pancreatic tumors, which makes it an effective therapy for pancreatic cancer. PMID:26405195

  20. [Chronic pancreatitis, acute pancreatitis].

    PubMed

    Mabuchi, T; Katada, N; Nishimura, D; Hoshino, H; Shimizu, F; Suzuki, R; Sano, H; Kato, K

    1998-11-01

    MRCP has been recognized as a safe and noninvasive diagnostic method. In the present study we evaluated the usefulness of MRCP in diagnosis of chronic and acute pancreatitis. Two-dimensional fast asymmetric spin-echo (FASE) MRCP was performed in 40 patients with chronic pancreatitis and 13 with acute pancreatitis. In 29 patients (72.5%) with chronic pancreatitis and 9 (66.7%) with acute pancreatitis, main pancreatic duct (MPD) was visualized entirely. MRCP could demonstrate the characteristic findings of chronic pancreatitis such as dilatation and irregularity of MPD in most cases. In acute pancreatitis, MRCP indicated that MPD was normal in diameter, but irregular in configuration compared with that of the control group. MRCP may facilitate the diagnosis of chronic and acute pancreatitis.

  1. Prognostic and Functional Significance of MAP4K5 in Pancreatic Cancer

    PubMed Central

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

    2016-01-01

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

  2. Large molecule protein feeding during the suckling period is required for the development of pancreatic digestive functions in rats.

    PubMed

    Kinouchi, Toshi; Koyama, Satomi; Harada, Etsumori; Yajima, Takaji

    2012-12-15

    We examined if large molecule protein feeding during the suckling period is prerequisite for the proper development of pancreatic digestive functions. Most amino acids in breast milk exist as the constituent of large proteins and not as oligopeptides or free amino acids. Accumulating evidence indicates the nutritional importance of large protein feeding for suckling infants; however, evidence on the physiological significance remains small. We thus artificially reared rat pups on a standard rat formula with milk protein or a formula with milk protein hydrolysate from 7 to 21 days of age, and thereafter, fed a standard solid diet until 42 days of age. Pancreas weight and the stock of pancreatic digestive enzymes in the hydrolysate-fed rats were significantly lower than those in the protein-fed rats during and also after the suckling period. Plasma insulin, a stimulator of amylase synthesis, was also significantly low in the hydrolysate-fed rats compared with the protein-fed rats. At 28 days of age, we evaluated the pancreatic secretory ability in response to dietary protein and cholecystokinin (CCK) by means of pancreatic duct cannulation. Pancreatic secretion stimulated by dietary protein in the hydrolysate-fed rats was significantly weaker than that in the protein-fed rats. No significant difference was observed in the increasing rate of pancreatic enzyme secretion in response to CCK between the two groups. These results suggest that the presence of large proteins in breast milk is significant for the development of pancreatic digestive functions and the outcomes could remain even later on in life.

  3. Preservation of beta cell function after pancreatic islet autotransplantation: University of Chicago experience.

    PubMed

    Savari, Omid; Golab, Karolina; Wang, Ling-Jia; Schenck, Lindsay; Grose, Randall; Tibudan, Martin; Ramachandran, Sabarinathan; Chon, W James; Posner, Mitchell C; Millis, J Michael; Matthews, Jeffrey B; Gelrud, Andres; Witkowski, Piotr

    2015-04-01

    The aim of the study was to assess the rate of insulin independence in patients after total pancreatectomy (TP) and islet autotransplantation in our center. TP followed by islet autotransplantation was performed in 10 patients. Severe unrelenting pain associated with chronic pancreatitis was the major indication for surgery. Islets were isolated using the modified Ricordi method and infused through the portal vein. Exogenous insulin therapy was implemented for at least two months posttransplant to support islet engraftment and was subsequently weaned off, if possible. Median follow-up was 26 months (range, 2 to 60 months). Median islet yield was 158,860 islet equivalents (IEQ) (range, 40,203 to 330,472 IEQ) with an average islet yield of 2,478 IEQ/g (range, 685 to 6,002 IEQ/g) of processed pancreas. One patient developed transient partial portal vein thrombosis, which resolved without sequela. Five (50%) patients are currently off insulin with excellent glucose control and HbA1c below 6. Patients who achieved and maintained insulin independence were transplanted with significantly more islets (median, 202,291 IEQ; range, 145,000 to 330,474 IEQ) than patients who required insulin support (64,348 IEQ; range, 40,203 to 260,476 IEQ; P < 0.05). Patient body mass index and time of chronic pancreatitis prior transplant procedure did not correlate with the outcome. The remaining five patients, who require insulin support, had present C-peptide in blood and experience good glucose control without incidence of severe hypoglycemic episodes. Islet autotransplantation efficiently preserved beta cell function in selected patients with chronic pancreatitis and the outcome correlated with transplanted islet mass.

  4. MicroRNA-7 functions as a tumor-suppressor gene by regulating ILF2 in pancreatic carcinoma.

    PubMed

    Bi, Yiliang; Shen, Wei; Min, Min; Liu, Yan

    2017-04-01

    Interleukin enhancer binding factor 2 (ILF2) has been found to be markedly upregulated in pancreatic carcinoma and is involved in the pathogenesis of pancreatic carcinoma. Thus, ILF2 may be a potential target for therapy. Yet, the regulatory mechanisms of ILF2 in pancreatic carcinoma remain largely elusive. In the present study, we demonstrated that ILF2 functioned as an oncogene and regulated epithelial-mesenchymal transition (EMT)-associated genes in pancreatic carcinoma PANC-1 cells. MicroRNA-7 (miR-7) suppressed ILF2 mRNA expression and the protein level in PANC-1 cells. Contrary to ILF2, miRNA-7 functioned as a tumor-suppressor gene and negatively regulated EMT-associated genes in the PANC-1 cells. Curcumin, a polyphenol natural product isolated from the rhizome of the plant Curcuma longa, has emerged as a promising anticancer therapeutic agent. We found that treatment with curcumin increased miR-7 expression and suppressed ILF2 protein in the PANC-1 cells. Thus, we identified ILF2 as a new downstream target gene of curcumin. The results revealed that ILF2 is regulated by miR-7 and suggest that downregulation of miR-7 may be an important factor for the ILF2 overexpression in pancreatic carcinoma.

  5. MicroRNA-7 functions as a tumor-suppressor gene by regulating ILF2 in pancreatic carcinoma

    PubMed Central

    Bi, Yiliang; Shen, Wei; Min, Min; Liu, Yan

    2017-01-01

    Interleukin enhancer binding factor 2 (ILF2) has been found to be markedly upregulated in pancreatic carcinoma and is involved in the pathogenesis of pancreatic carcinoma. Thus, ILF2 may be a potential target for therapy. Yet, the regulatory mechanisms of ILF2 in pancreatic carcinoma remain largely elusive. In the present study, we demonstrated that ILF2 functioned as an oncogene and regulated epithelial-mesenchymal transition (EMT)-associated genes in pancreatic carcinoma PANC-1 cells. MicroRNA-7 (miR-7) suppressed ILF2 mRNA expression and the protein level in PANC-1 cells. Contrary to ILF2, miRNA-7 functioned as a tumor-suppressor gene and negatively regulated EMT-associated genes in the PANC-1 cells. Curcumin, a polyphenol natural product isolated from the rhizome of the plant Curcuma longa, has emerged as a promising anticancer therapeutic agent. We found that treatment with curcumin increased miR-7 expression and suppressed ILF2 protein in the PANC-1 cells. Thus, we identified ILF2 as a new downstream target gene of curcumin. The results revealed that ILF2 is regulated by miR-7 and suggest that downregulation of miR-7 may be an important factor for the ILF2 overexpression in pancreatic carcinoma. PMID:28259961

  6. Functional tests for myocardial ischemia

    SciTech Connect

    Levinson, J.R.; Guiney, T.E.; Boucher, C.A. )

    1991-01-01

    Functional tests for myocardial ischemia are numerous. Most depend upon a combination of either exercise or pharmacologic intervention with analysis of the electrocardiogram, of regional perfusion with radionuclide imaging, or of regional wall motion with radionuclide imaging or echocardiography. While each test has unique features, especially at the research level, they are generally quite similar in clinical practice, so the clinician is advised to concentrate on one or two in which local expertise is high.22 references.

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

    PubMed Central

    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 down- regulated 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. PMID:26695692

  8. Sulforaphane Protects against High Cholesterol-Induced Mitochondrial Bioenergetics Impairments, Inflammation, and Oxidative Stress and Preserves Pancreatic β-Cells Function

    PubMed Central

    Tan, Kah Ni; Gotteland, Martin

    2017-01-01

    Cholesterol plays an important role in inducing pancreatic β-cell dysfunction, leading to an impaired insulin secretory response to glucose. This study aimed to determine the protective effects of sulforaphane, a natural isothiocyanate Nrf2-inducer, against cholesterol-induced pancreatic β-cells dysfunction, through molecular and cellular mechanisms involving mitochondrial bioenergetics. Sulforaphane prevented cholesterol-induced alterations in the coupling efficiency of mitochondrial respiration, improving ATP turnover and spare capacity, and averted the impairment of the electron flow at complexes I, II, and IV. Sulforaphane also attenuated the cholesterol-induced activation of the NFκB pathway, normalizing the expression of pro- and anti-inflammatory cytokines. In addition, it also inhibited the decrease in sirtuin 1 expression and greatly increased Pgc-1α expression in Min6 cells. Sulforaphane increased the expression of antioxidant enzymes downstream of the Nrf2 pathway and prevented lipid peroxidation induced by cholesterol. The antioxidant and anti-inflammatory properties of sulforaphane and its ability to protect and improve mitochondrial bioenergetic function contribute to its protective action against cholesterol-induced pancreatic β-cell dysfunction. Our data provide a scientifically tested foundation upon which sulforaphane can be developed as nutraceutical to preserve β-cell function and eventually control hyperglycemia. PMID:28386307

  9. Comprehensive treatment of a functional pancreatic neuroendocrine tumor with multifocal liver metastases.

    PubMed

    Wang, Wei; Seeruttun, Sharvesh Raj; Fang, Cheng; Zhou, Zhiwei

    2014-08-01

    A 64-year-old man was admitted to the Sun Yat-Sen University Cancer Center with chief complaints of recurrent abdominal pain and diarrhea for about 3 years and with a history of surgical repair for intestinal perforation owing to stress ulcer. Positron emission tomography (PET)/computed tomography (CT) demonstrated a primary tumor on the pancreatic tail with multifocal liver metastases. Pathological and immunohistochemistry staining revealed the lesion to be a pancreatic neuroendocrine tumor (pNET). According to the latest World Health Organization (WHO, 2013) classification, the tumor was classified as stage IV functional G1 pNET. After referral to the multidisciplinary treatment board (MDT), the patient was started on periodic dose of omeprazole, somatostatin analogues and Interferon α (IFNα) and had scanning follow-ups. Based upon the imaging results, CT-guided radioactive iodine-125 ((125)I) seeds implantation therapy, radiofrequency ablation therapy (RFA) or microwave ablation technique were chosen for the treatment of the primary tumor. Transarterial chemoembolization (TACE), RFA and microwave ablation techniques were decided upon for liver metastases. The patient showed beneficial response to the treatment with clinically manageable low-grade side effects and attained partial remission (RECIST criteria) with a good quality of life.

  10. Simulated Microgravity Combined with Polyglycolic Acid Scaffold Culture Conditions Improves the Function of Pancreatic Islets

    PubMed Central

    Song, Yimin; Wei, Zheng; Song, Chun; Xie, Shanshan; Feng, Jinfa; Fan, Jiehou; Zhang, Zengling; Shi, Yubo

    2013-01-01

    The in vitro culture of pancreatic islets reduces their immunogenicity and prolongs their availability for transplantation. Both simulated microgravity (sMG) and a polyglycolic acid scaffold (PGA) are believed to confer advantages to cell culture. Here, we evaluated the effects of sMG combined with a PGA on the viability, insulin-producing activity and morphological alterations of pancreatic islets. Under PGA-sMG conditions, the purity of the islets was ≥85%, and the islets had a higher survival rate and an increased ability to secrete insulin compared with islets cultured alone in the static, sMG, or PGA conditions. In addition, morphological analysis under scanning electron microscopy (SEM) revealed that the PGA-sMG treatment preserved the integral structure of the islets and facilitated islet adhesion to the scaffolds. These results suggest that PGA-sMG coculture has the potential to improve the viability and function of islets in vitro and provides a promising method for islet transplantation. PMID:24024182

  11. [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.

  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. Chronic pancreatitis

    MedlinePlus

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... hospital for: Pain medicines Fluids given through a vein (IV) Stopping food or fluid by mouth to ...

  14. Anti-Donor HLA Antibody Response After Pancreatic Islet Grafting: Characteristics, Risk Factors, and Impact on Graft Function.

    PubMed

    Pouliquen, E; Baltzinger, P; Lemle, A; Chen, C-C; Parissiadis, A; Borot, S; Frimat, L; Girerd, S; Berney, T; Lablanche, S; Benhamou, P Y; Morelon, E; Badet, L; Dubois, V; Kessler, L; Thaunat, O

    2017-02-01

    Pancreatic islet grafting restores endogenous insulin production in type 1 diabetic patients, but long-term outcomes remain disappointing as a result of immunological destruction of allogeneic islets. In solid organ transplantation, donor-specific anti-HLA antibodies (DSA) are the first cause of organ failure. This retrospective multicentric study aimed at providing in-depth characterization of DSA response after pancreatic islet grafting, identifying the risk factor for DSA generation and determining the impact of DSA on graft function. Forty-two pancreatic islet graft recipients from the Groupe Rhin-Rhône-Alpes-Genève pour la Greffe d'Ilots de Langerhans consortium were enrolled. Pre- and postgrafting sera were screened for the presence of DSA and their ability to activate complement. Prevalence of DSA was 25% at 3 years postgrafting. The risk of sensitization increased steeply after immunosuppressive drug withdrawal. DSA repertoire diversity correlated with the number of HLA and eplet mismatches. DSA titer was significantly lower from that observed in solid organ transplantation. No detected DSA bound the complement fraction C3d. Finally, in contrast with solid organ transplantation, DSA did not seem to negatively affect pancreatic islet graft survival. This might be due to the low DSA titers, specific features of IgG limiting their ability to activate the complement and/or the lack of allogenic endothelial targets in pancreatic islet grafts.

  15. Sensing and Sensibility: Single-Islet-based Quality Control Assay of Cryopreserved Pancreatic Islets with Functionalized Hydrogel Microcapsules.

    PubMed

    Chen, Wanyu; Shu, Zhiquan; Gao, Dayong; Shen, Amy Q

    2016-01-21

    Despite decades of research and clinical studies of islet transplantations, finding simple yet reliable islet quality assays that correlate accurately with in vivo potency is still a major challenge, especially for real-time and single-islet-based quality assessment. Herein, proof-of-concept studies of a cryopreserved microcapsule-based quality control assays are presented for single islets. Individual rat pancreatic islets and fluorescent oxygen-sensitive dye (FOSD) are encapsulated in alginate hydrogel microcapsules via a microfluidic device. To test the susceptibility of the microcapsules and the FOSD to cryopreservation, the islet microcapsules containing FOSD are cryopreserved and the islet functionalities (adenosine triphosphate, static insulin release measurement, and oxygen consumption rate) are assessed after freezing and thawing steps. The cryopreserved islet capsules with FOSD remain functional after encapsulation and freezing/thawing procedures, validating a simple yet reliable individual-islet-based quality control method for the entire islet processing procedure prior to transplantation. This work also demonstrates that the functionality of cryopreserved islets can be improved by introducing trehalose into the routinely used cryoprotectant dimethyl sulfoxide. The functionalized alginate hydrogel microcapsules with embedded FOSD and optimized cryopreservation protocol presented in this work serve as a versatile islet quality assay and offer tremendous promise for tackling existing challenges in islet transplantation procedures.

  16. 78 FR 52929 - Scientific Information Request on Imaging Tests for the Diagnosis and Staging of Pancreatic...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-27

    ..., PET-CT, MRI) for diagnosis of pancreatic adenocarcinoma in adults with suspicious symptoms? a. What is... effectiveness of imaging techniques (e.g., MDCT angiography 3D reconstruction, other MDCT, EUS-FNA, PET-CT, MRI..., EUS-FNA, PET- CT, MRI) when used to diagnose and/or stage pancreatic adenocarcinoma? a. How...

  17. Intermediate-range sweat chloride concentration and Pseudomonas bronchitis. A cystic fibrosis variant with preservation of exocrine pancreatic function.

    PubMed

    Stern, R C; Boat, T F; Abramowsky, C R; Matthews, L W; Wood, R E; Doershuk, C F

    1978-06-23

    We studied the clinical and laboratory characteristics of seven patients with sweat chloride concentration consistently between 40 and 60 mEq/liter. Each has chronic Pseudomonas bronchitis, and all lack digestive symptoms. Laboratory findings indicate the preservation of exocrine pancreatic function. The patients include two of five children in one family and two of four in another. In a third family, one of five siblings has an intermediate sweat chloride concentration, but another has a typical fibrosis value (105 mEq/liter). One patient died of respiratory failure; results of an autopsy showed bronchiolectasis typical of cystic fibrosis, but minimal pancreatic changes. The data suggest a genetic basis for this variant of cystic fibrosis. These patients may be homozygous for a portion of a closely linked multigene cystic fibrosis locus or may have modifier genes that ameliorate the pancreatic and sweat lesions.

  18. Oral administration of soybean peptide Vglycin normalizes fasting glucose and restores impaired pancreatic function in Type 2 diabetic Wistar rats.

    PubMed

    Jiang, Hua; Feng, Jueping; Du, Zhongxia; Zhen, Hui; Lin, Mei; Jia, Shaohui; Li, Tao; Huang, Xinyuan; Ostenson, Claes-Goran; Chen, Zhengwang

    2014-09-01

    Vglycin, a natural 37-residue polypeptide isolated from pea seeds in which six half-cysteine residues are embedded in three pairs of disulfide bonds, is resistant to digestive enzymes and has antidiabetic potential. To investigate the pharmacological activity of Vglycin in vivo and to examine the mechanisms involved, the therapeutic effect of Vglycin in diabetic rats was examined. Diabetes was induced in Wistar rats by high-fat diet and multiple streptozotocin intraperitoneal injections. Diabetic rats were treated daily with Vglycin for 4 weeks. Body weight, food intake, fasting plasma glucose and insulin levels were assayed weekly. Glucose and insulin tolerance tests were conducted on Day 29. Subsequently, levels of p-Akt in the liver and pancreas and cleaved PARP, Pdx-1 and insulin in the pancreas were detected by immunoblotting. The morphology of the pancreas and the insulin expression in the pancreas were analyzed by hematoxylin-eosin staining and immunohistochemistry, respectively. Furthermore, human liver-derived cell lines were used to explore the in vitro effects of Vglycin on insulin sensitivity and glucose uptake. Chronic treatment with Vglycin normalized fasting glucose levels in diabetic rats. The improvement in glucose homeostasis and the increased insulin sensitivity mediated by restored insulin signaling likely contributed to decreased food intake and reduced body weight. Vglycin protected pancreatic cells from damage by streptozotocin. Although insulin synthesis and secretion in impaired β-cell were not significantly elevated, islets morphology was improved in the Vglycin-treated groups. These results suggest that Vglycin could be useful in Type 2 diabetes for restoring impaired insulin signaling, glucose tolerance and pancreatic function.

  19. Retracted: Identification of Novel Biomarkers for Pancreatic Cancer Using Integrated Transcriptomics With Functional Pathways Analysis.

    PubMed

    Zhang, Xuan; Tong, Pan; Chen, Jinyun; Pei, Zenglin; Zhang, Xiaoyan; Chen, Weiping; Xu, Jianqing; Wang, Jin

    2016-02-22

    Retraction: 'Identification of Novel Biomarkers for Pancreatic Cancer Using Integrated Transcriptomics With Functional Pathways Analysis' by Zhang, X., Tong, P., Chen, J., Pei, Z., Zhang, X., Chen, W., Xu, J. and Wang, J. The above article from the Journal of Cellular Physiology, published online on 10 March 2016 in Wiley Online Library as Early View (http://onlinelibrary.wiley.com/enhanced/doi/10.1002/jcp.25353/), has been retracted by agreement between Gary Stein, the journal's Editor-in-Chief, and Wiley Periodicals, Inc. The retraction has been agreed following an investigation at the University of Texas, MD Anderson Cancer Center, which confirmed that the article was submitted and approved for publication by Dr. Jin Wang without acknowledgement of NIH funding received or the consent and authorship of Dr. Ann Killary and Dr. Subrata Sen, with whom the manuscript was originally drafted.

  20. [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%.

  1. Pancreatic Fat Is Associated With Metabolic Syndrome and Visceral Fat but Not Beta-Cell Function or Body Mass Index in Pediatric Obesity

    PubMed Central

    Staaf, Johan; Labmayr, Viktor; Paulmichl, Katharina; Manell, Hannes; Cen, Jing; Ciba, Iris; Dahlbom, Marie; Roomp, Kirsten; Anderwald, Christian-Heinz; Meissnitzer, Matthias; Schneider, Reinhard; Forslund, Anders; Widhalm, Kurt; Bergquist, Jonas; Ahlström, Håkan; Bergsten, Peter; Weghuber, Daniel; Kullberg, Joel

    2017-01-01

    Objective Adolescents with obesity have increased risk of type 2 diabetes and metabolic syndrome (MetS). Pancreatic fat has been related to these conditions; however, little is known about associations in pediatric obesity. The present study was designed to explore these associations further. Methods We examined 116 subjects, 90 with obesity. Anthropometry, MetS, blood samples, and oral glucose tolerance tests were assessed using standard techniques. Pancreatic fat fraction (PFF) and other fat depots were quantified using magnetic resonance imaging. Results The PFF was elevated in subjects with obesity. No association between PFF and body mass index-standard deviation score (BMI-SDS) was found in the obesity subcohort. Pancreatic fat fraction correlated to Insulin Secretion Sensitivity Index-2 and Homeostatic Model Assessment of Insulin Resistance in simple regression; however, when using adjusted regression and correcting for BMI-SDS and other fat compartments, PFF correlated only to visceral adipose tissue and fasting glucose. Highest levels of PFF were found in subjects with obesity and MetS. Conclusions In adolescents with obesity, PFF is elevated and associated to MetS, fasting glucose, and visceral adipose tissue but not to beta-cell function, glucose tolerance, or BMI-SDS. This study demonstrates that conclusions regarding PFF and its associations depend on the body mass features of the cohort. PMID:27941426

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

    PubMed

    Johansson, Ulrika; Ria, Massimiliano; Åvall, Karin; 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

  3. 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

  4. 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.

  5. Evolutionary and Functional Novelty of Pancreatic Ribonuclease: a Study of Musteloidea (order Carnivora)

    PubMed Central

    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

  6. 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

    2014-05-27

    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.

  7. Impaired pancreatic beta cell function in the fetal GK rat. Impact of diabetic inheritance.

    PubMed Central

    Serradas, P; Gangnerau, M N; Giroix, M H; Saulnier, C; Portha, B

    1998-01-01

    The Goto-Kakisaki (GK) rat is a genetic model of non-insulin-dependent diabetes. At 21.5 d of age we found that GK fetuses had an increased plasma glucose concentration, a decreased plasma insulin level, and a reduced pancreatic beta cell mass. To investigate the beta cell function during fetal life we used a hyperglycemic clamp protocol applied to the mothers, which allowed us to obtain a steady-state hyperglycemia in the corresponding fetuses. At variance, with Wistar (W) fetuses, plasma insulin concentration in GK fetuses did not rise in response to hyperglycemia. In contrast, GK fetal pancreas released insulin in response to glucose in vitro to the same extent as W fetal pancreas. Such a discrepancy between the in vivo and in vitro results suggests that the lack of pancreatic reactivity to glucose as seen in vivo is extrinsic to the fetal GK beta cell. Finally, the importance of gestational hyperglycemia was investigated by performing crosses between GK and W rats. Fetuses issued from crosses between W mother and GK father or GK mother and W father had a beta cell mass close to normal values and were still able to increase their plasma insulin levels in response to hyperglycemia in vivo. Our data suggest that hyperglycemia in utero does not influence the severity of the decrease of the beta cell mass or the lack of the insulin secretory response to glucose in the fetal GK rat. Moreover they indicate that conjunction of GK genes originating from both parents is necessary in order for these defects to be fully expressed. PMID:9466985

  8. 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

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

    PubMed Central

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

    2015-01-01

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

  10. Characterization of succinate dehydrogenase and alpha-glycerophosphate dehydrogenase in pancreatic islets.

    PubMed

    Lenzen, S; Panten, U

    1983-12-01

    Succinate dehydrogenase activities in homogenates of rat and ob/ob mouse pancreatic islets were only 13% of the activities in homogenates of liver and were also several times lower than in homogenates of pancreatic acinar tissue. This indicates that the content of mitochondria in pancreatic islet cells is very low. The very low activity of succinate dehydrogenase is in agreement with the low mitochondrial volume in the cytoplasmic ground substance of pancreatic islet cells as observed in morphometric studies. This may represent the poor equipment of pancreatic islet cells with electron transport chains and thus provide a regulatory role for the generation of reducing equivalents and chemical energy for the regulation of insulin secretion. The activities of succinate dehydrogenase in tissue homogenates of pancreatic islets, pancreatic acinar tissue, and liver were significantly inhibited by malonate and diazoxide but not by glucose, mannoheptulose, streptozotocin, or verapamil. Tolbutamide inhibited only pancreatic islet succinate dehydrogenase significantly, providing evidence for a different behavior of pancreatic islet cell mitochondria. Therefore diazoxide and tolbutamide may affect pancreatic islet function through their effects on succinate dehydrogenase activity. The activities of alpha-glycerophosphate dehydrogenase in homogenates of pancreatic islets and liver from rats and ob/ob mice were in the same range, while activities in homogenates of pancreatic acinar tissue were lower. None of the test agents affected alpha-glycerophosphate dehydrogenase activity. Thus the results provide no support for the recent contention that alpha-glycerophosphate dehydrogenase activity may be critical for the regulation of insulin secretion.

  11. The Fas pathway is involved in pancreatic β cell secretory function

    PubMed Central

    Schumann, Desiree M.; Maedler, Kathrin; Franklin, Isobel; Konrad, Daniel; Størling, Joachim; Böni-Schnetzler, Marianne; Gjinovci, Asllan; Kurrer, Michael O.; Gauthier, Benoit R.; Bosco, Domenico; Andres, Axel; Berney, Thierry; Greter, Melanie; Becher, Burkhard; Chervonsky, Alexander V.; Halban, Philippe A.; Mandrup-Poulsen, Thomas; Wollheim, Claes B.; Donath, Marc Y.

    2007-01-01

    Pancreatic β cell mass and function increase in conditions of enhanced insulin demand such as obesity. Failure to adapt leads to diabetes. The molecular mechanisms controlling this adaptive process are unclear. Fas is a death receptor involved in β cell apoptosis or proliferation, depending on the activity of the caspase-8 inhibitor FLIP. Here we show that the Fas pathway also regulates β cell secretory function. We observed impaired glucose tolerance in Fas-deficient mice due to a delayed and decreased insulin secretory pattern. Expression of PDX-1, a β cell-specific transcription factor regulating insulin gene expression and mitochondrial metabolism, was decreased in Fas-deficient β cells. As a consequence, insulin and ATP production were severely reduced and only partly compensated for by increased β cell mass. Up-regulation of FLIP enhanced NF-κB activity via NF-κB-inducing kinase and RelB. This led to increased PDX-1 and insulin production independent of changes in cell turnover. The results support a previously undescribed role for the Fas pathway in regulating insulin production and release. PMID:17299038

  12. 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

  13. 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?

  14. Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic β-cell function.

    PubMed

    Gilbert, Elizabeth R; Liu, Dongmin

    2013-02-01

    Type 2 diabetes is a result of chronic insulin resistance and loss of functional pancreatic β-cell mass. Strategies to preserve β-cell mass and a greater understanding of the mechanisms underlying β-cell turnover are needed to prevent and treat this devastating disease. Genistein, a naturally occurring soy isoflavone, is reported to have numerous health benefits attributed to multiple biological functions. Over the past 10 years, numerous studies have demonstrated that genistein has anti-diabetic effects, in particular, direct effects on β-cell proliferation, glucose-stimulated insulin secretion and protection against apoptosis, independent of its functions as an estrogen receptor agonist, antioxidant, or tyrosine kinase inhibitor. Effects are structure-specific and not common to all flavonoids. While there are limited data on the effects of genistein consumption in humans with diabetes, there are a plethora of animal and cell-culture studies that demonstrate a direct effect of genistein on β-cells at physiologically relevant concentrations (<10 μM). The effects appear to involve cAMP/PKA signaling and there are some studies that suggest an effect on epigenetic regulation of gene expression. This review focuses on the anti-diabetic effects of genistein in both in vitro and in vivo models and potential mechanisms underlying its direct effects on β-cells.

  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. 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 ...

  17. Pancreatic pseudocyst

    MedlinePlus

    ... More Acute pancreatitis Chronic pancreatitis Pancreatic abscess Shock Review Date 10/27/2015 Updated by: Subodh K. ... gastroenterologist with Gastrointestinal Specialists of Georgia, Austell, GA. Review provided by VeriMed Healthcare Network. Also reviewed by ...

  18. [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.

  19. A rare case of metastasized non-functional pancreatic neuroendocrine tumor with a good long-term survival

    PubMed Central

    Mirică, A; Bădărău, IA; Mirică, R; Păun, S; Păun, DL

    2016-01-01

    Background: Non-functional neuroendocrine tumors of the pancreas (NF-pNETs) are a varied group of extremely rare malignancies. The majority of patients already have liver metastases at the diagnosis moment, thus, treatment options are restricted, and the survival rate is reserved. Case report: We presented the case of 59-year-old patient, diagnosed with non-functional well-differentiated pancreatic neuroendocrine tumor grade II (NET G2) with the presence of chromogranin A, synaptophysin and somatostatin receptor 2, together with liver and bone metastases. Patient underwent a surgical excision of the pancreatic tumor, started long-acting somatostatin analogues (octreotide), interferon therapy for liver metastases and local radiotherapy for bone metastases. After one year, the patient developed diabetes, needing insulin therapy. At approximately three years after the diagnosis, the patient was still living, had a good quality of life, and was free of local recurrence of the tumor or other metastases. Conclusion: Our case report presented a rare case of metastatic non-functional well-differentiated pancreatic neuroendocrine tumor, involving a multidisciplinary therapeutic approach in order to obtain a good long-term survival. PMID:27928440

  20. A rare case of metastasized non-functional pancreatic neuroendocrine tumor with a good long-term survival.

    PubMed

    A, Mirică; Ia, Bădărău; R, Mirică; S, Păun; Dl, Păun

    2016-01-01

    Background: Non-functional neuroendocrine tumors of the pancreas (NF-pNETs) are a varied group of extremely rare malignancies. The majority of patients already have liver metastases at the diagnosis moment, thus, treatment options are restricted, and the survival rate is reserved. Case report: We presented the case of 59-year-old patient, diagnosed with non-functional well-differentiated pancreatic neuroendocrine tumor grade II (NET G2) with the presence of chromogranin A, synaptophysin and somatostatin receptor 2, together with liver and bone metastases. Patient underwent a surgical excision of the pancreatic tumor, started long-acting somatostatin analogues (octreotide), interferon therapy for liver metastases and local radiotherapy for bone metastases. After one year, the patient developed diabetes, needing insulin therapy. At approximately three years after the diagnosis, the patient was still living, had a good quality of life, and was free of local recurrence of the tumor or other metastases. Conclusion: Our case report presented a rare case of metastatic non-functional well-differentiated pancreatic neuroendocrine tumor, involving a multidisciplinary therapeutic approach in order to obtain a good long-term survival.

  1. 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...

  2. 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...

  3. 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...

  4. Correction of malnutrition and maldigestion with enzyme supplementation in patients with surgical suppression of exocrine pancreatic function.

    PubMed

    Braga, M; Cristallo, M; De Franchis, R; Mangiagalli, A; Agape, D; Primignani, M; Di Carlo, V

    1988-12-01

    We studied the occurrence and extent of malnutrition and maldigestion in 13 patients who underwent pancreatoduodenectomy (PD) and injection of Neoprene (polychloroprene) (NI) into the duct of Wirsung, which results in sclerosis of hte acinar pancreatic tissue, but spares the endocrine function. At discharge, patients under took an enzyme supplementation regimen with pancreatin (18, 00 United States Pharmacopoeia units of lipase per meal). Patients were rehospitalized 24.9 months after PD plus NI to undergo nutritional and metabolic evaluation (hospital control). Nutritional status was evaluated by measuring the serum albumin level, total iron binding capacity and total lymphocyte count. Digestive function was assessed by the D-xylose tolerance test and determination of fecal fat excretion. Patients were then discharged with pancrelipase, enteric-coated microspheres (ECM) supplementation (16,050 United States Pharmacopoeia units of lipase per meal). Malnutrition, defined as the occurrence of at least two abnormal nutritional parameters, was observed in six patients at hospital control. After six months on pancrelipase ECM, the nutritional status was re-evaluated in nine patients (three previously malnourished) who were all well nourished. The mean body weight was 84.7 per cent of usual body weight at discharge after PD plus NI and raised to 88.0 per cent at the hospital control (p less than 0.01) and to 93.7 per cent )p less than 0.05) after six months on pancrelipase ECM. At hospital control, results from the D-xylose test were normal in all patients, and steatorrhea dropped from 33.6 grams per day without enzyme supplementation to 15.3 grams per day with pancrelipase ECM (16,050 United States Pharmacopoeia units of lipase per meal). Steatorrhea was incompletely but satisfactorily corrected by pancrelipase ECM. On supplementation therapy with pancrelipase ECM, patients recover a good deal of the body weight and normalize the biochemical indices of malnutrition.

  5. Pancreatic Exocrine Insufficiency in Pancreatic Cancer

    PubMed Central

    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J.-Matthias

    2017-01-01

    Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor’s metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes. PMID:28241470

  6. 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.

  7. Isolation and functional expression of human pancreatic peptidylglycine alpha-amidating monooxygenase.

    PubMed

    Tateishi, K; Arakawa, F; Misumi, Y; Treston, A M; Vos, M; Matsuoka, Y

    1994-11-30

    Pancreastatin (PST) is processed from chromogranin A and the C-terminal amide of the peptide is an absolute requirement for biological activities. Human pancreatic carcinoma cells QGP-1 which produce both chromogranin A and PST were used to isolate cDNAs encoding two forms of peptidylglycine alpha-amidating monooxygenase (PAM). The two forms are a full length bifunctional enzyme and a variant lacking the transmembrane domain-coding region. When the cDNAs of these two forms were expressed in COS-7 cells, cells transfected with the predicted soluble form released into the culture medium a very much higher amidating activity which converts human chromogranin A-(273-302) to PST-29. The optimal pH for amidating activity was 5.4 and Cu2+, ascorbate and catalase were required as cofactors for the both forms of PAM. Km values for the membrane-bound and the soluble forms of PAM were 15.7 +/- 3.1 microM and 12.4 +/- 1.6 microM, respectively. These results demonstrate that both forms of PAM can function in the posttranslational processing of chromogranin A to PST in the environment of a secretory vesicle.

  8. Epidrug-induced upregulation of functional somatostatin type 2 receptors in human pancreatic neuroendocrine tumor cells.

    PubMed

    Veenstra, Marije J; van Koetsveld, Peter M; Dogan, Fadime; Farrell, William E; Feelders, Richard A; Lamberts, Steven W J; de Herder, Wouter W; Vitale, Giovanni; Hofland, Leo J

    2016-05-19

    Somatostatin receptors are a pivotal target for treatment of pancreatic neuroendocrine tumors (pNET), either with somatostatin analogues (SSA) or radiolabeled SSA. The highest affinity target for the most commonly used SSA is the somatostatin receptor type 2 (sst2). An important factor that may complicate treatment efficacy, is the variable number of receptors expressed on pNETs. Gene expression is subject to complex regulation, in which epigenetics has a central role. In this study we explored the possible role of epigenetic modifications in the variations in sst2 expression levels in two human pNET cell lines, BON-1 and QGP-1. We found upregulation of sst2 mRNA after treatment with the epidrugs 5-aza-2'-deoxycytidine (5-aza-dC) and valproic acid (VPA), an increased uptake of radiolabeled octreotide, as well as increased sensitivity to the SSA octreotide in functional cAMP inhibition. At epigenetic level we observed low methylation levels of the sst2 gene promoter region irrespective of expression. Activating histone mark H3K9Ac can be regulated with epidrug treatment, with an angle of effect corresponding to the effect on mRNA expression. Repressive histone mark H3K27me3 is not regulated by either 5-aza-dC or VPA. We conclude that epidrug treatment, in particular with combined 5-aza-dC and VPA treatment, might hold promise for improving and adding to current SSA treatment strategies of patients with pNETs.

  9. 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

  10. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

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

    PubMed

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

    2016-02-16

    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.

  12. 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

  13. Overexpression and biological function of IQGAP3 in human pancreatic cancer

    PubMed Central

    Xu, Weihong; Xu, Bin; Yao, Yiting; Yu, Xiaoling; Cao, Hua; Zhang, Jun; Liu, Jie; Sheng, Huiming

    2016-01-01

    IQGAP3 (IQ motif containing GTPase activating protein3) belongs to IQGAP family. Recent studies have investigated that IQGAP3 was overexpressed in several tumor tissues. This study was designed to explore the expression and role of IQGAP3 in pancreatic cancer, a highly lethal disease. IQGAP3 mRNA expression was significantly increased in pancreatic cancer tissues, compared with non-cancerous tissues. Moreover, its expression was strongly associated with tumor size, differentiation, lymph node metastasis and patients’ overall survival. Gene set enrichment analysis (GSEA) on The Cancer Genome Atlas (TCGA) dataset showed that cell apoptosis, metastasis and Cdc42 pathways were strongly associated with IQGAP3 expression in pancreatic cancer patients. Knocking down of IQGAP3 in two pancreatic cancer cell lines with high level of IQGAP3 (BXPC-3 and SW1990) significantly inhibited cell proliferation, migration and invasion, and induced cell apoptosis. Moreover, silencing of IQGAP3 also affected the expression of cell apoptosis-, metastasis- and Cdc42 pathway-related proteins. Cdc42 knockdown had similar inhibitory effects on the cellular behavior of BXPC-3 cells. In conclusion, IQGAP3 may act as an oncogene in pancreatic cancer through regulating Cdc42 expression. Our data suggest IQGAP3 might be a novel diagnostic marker and therapeutic target for this cancer. PMID:28078013

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2013-01-01

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

  16. 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 ...

  17. 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 ...

  18. What Are Lung Function Tests?

    MedlinePlus

    ... COPD How the Lungs Work Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... the Lungs Work Idiopathic Pulmonary Fibrosis Oxygen Therapy Sarcoidosis Stress Testing Rate This Content: Updated: December 9, ...

  19. A Panel of CA19-9, Ca125, and Ca15-3 as the Enhanced Test for the Differential Diagnosis of the Pancreatic Lesion

    PubMed Central

    Skulimowski, Aleksander; Durczyński, Adam; Kumor, Anna; Poznańska, Grażyna; Oleśna, Aleksandra; Rut, Joanna

    2017-01-01

    Background. Proper diagnosis of pancreatic lesion etiology is a challenging clinical dilemma. Studies suggest that surgery for suspected pancreatic ductal adenocarcinoma (PDAC) reveals a benign lesion in 5% to 13% of cases. The aim of our study was to assess whether routinely used biomarkers such as CA19-9, Ca125, Ca15-3, and CEA, when combined, can potentially yield an accurate test predicting pancreatic lesion etiology. Methods. We retrospectively analyzed data of 326 patients who underwent a diagnostic process due to pancreatic lesions of unknown etiology. Results. We found statistically significant differences in mean levels of all biomarkers. In logistic regression model, we applied levels CA19-9, Ca125, and Ca15-3 as variables. Two validation methods were used, namely, random data split into training and validation groups and bootstrapping. Afterward, we built ROC curve using the model that we had created, reaching AUC = 0,801. With an optimal cut-off point, it achieved specificity of 81,2% and sensitivity of 63,10%. Our proposed model has superior diagnostic accuracy to both CA19-9 (p = 0,0194) and CA125 (p = 0,0026). Conclusion. We propose a test that is superior to CA19-9 in a differential diagnosis of pancreatic lesion etiology. Although our test fails to reach exceptionally high accuracy, its feasibility and cost-effectiveness make it clinically useful. PMID:28356610

  20. Testing Properties of Boolean Functions

    DTIC Science & Technology

    2012-01-01

    think of Pno as forming the argument multiset Sno by choosing ` = k − e random columns from Q 103 without replacement, and including an additional e...Rno) ≤ dTV(Syes, Sno ). (10.2) This inequality can be extremely lossy, depending on the function gcore. However, since Theorem 10.1 applies for an...absence of additional restrictions on the class of functions considered, there is no obvious way to bound dTV(Ryes, Rno) except by dTV(Syes, Sno

  1. Carriers of Loss-of-Function Mutations in EXT Display Impaired Pancreatic Beta-Cell Reserve Due to Smaller Pancreas Volume

    PubMed Central

    Hassing, H . Carlijne; Kruit, Janine K.; Witjes, Julia J.; van de Sande, Michiel A. J.; Nederveen, Aart J.; Xu, Ding; Dallinga-Thie, Geesje M.; Esko, Jeffrey D.; Stroes, Erik S. G.; Nieuwdorp, Max

    2014-01-01

    Exotosin (EXT) proteins are involved in the chain elongation step of heparan sulfate (HS) biosynthesis, which is intricately involved in organ development. Loss of function mutations (LOF) in EXT1 and EXT2 result in hereditary exostoses (HME). Interestingly, HS plays a role in pancreas development and beta-cell function, and genetic variations in EXT2 are associated with an increased risk for type 2 diabetes mellitus. We hypothesized that loss of function of EXT1 or EXT2 in subjects with hereditary multiple exostoses (HME) affects pancreatic insulin secretion capacity and development. We performed an oral glucose tolerance test (OGTT) followed by hyperglycemic clamps to investigate first-phase glucose-stimulated insulin secretion (GSIS) in HME patients and age and gender matched non-affected relatives. Pancreas volume was assessed with magnetic resonance imaging (MRI). OGTT did not reveal significant differences in glucose disposal, but there was a markedly lower GSIS in HME subjects during hyperglycemic clamp (iAUC HME: 0.72 [0.46–1.16] vs. controls 1.53 [0.69–3.36] nmol·l−1·min−1, p<0.05). Maximal insulin response following arginine challenge was also significantly attenuated (iAUC HME: 7.14 [4.22–10.5] vs. controls 10.2 [7.91–12.70] nmol·l−1·min−1 p<0.05), indicative of an impaired beta-cell reserve. MRI revealed a significantly smaller pancreatic volume in HME subjects (HME: 72.0±15.8 vs. controls 96.5±26.0 cm3 p = 0.04). In conclusion, loss of function of EXT proteins may affect beta-cell mass and insulin secretion capacity in humans, and render subjects at a higher risk of developing type 2 diabetes when exposed to environmental risk factors. PMID:25541963

  2. 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.

  3. Chronic Pancreatitis in Children

    MedlinePlus

    ... Chronic Pancreatitis in Children Childhood Inherited Disorders Pancreatic Cancer Pancreatic Cancer Risks and Symptoms Staging of Pancreatic Cancer Treatment of Pancreatic Cancer Whipple Procedure Complementary Therapies Pancreatic Cancer Support ...

  4. Acute Pancreatitis in Children

    MedlinePlus

    ... Chronic Pancreatitis in Children Childhood Inherited Disorders Pancreatic Cancer Pancreatic Cancer Risks and Symptoms Staging of Pancreatic Cancer Treatment of Pancreatic Cancer Whipple Procedure Complementary Therapies Pancreatic Cancer Support ...

  5. 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

  6. [Pancreatic cancer stem cell].

    PubMed

    Hamada, Shin; Masamune, Atsushi; Shimosegawa, Tooru

    2015-05-01

    Prognosis of pancreatic cancer remains dismal due to the resistance against conventional therapies. Metastasis and massive invasion toward surrounding organs hamper radical resection. Small part of entire cancer cells reveal resistance against chemotherapy or radiotherapy, increased tumorigenicity and migratory phenotype. These cells are called as cancer stem cells, as a counter part of normal stem cells. In pancreatic cancer, several cancer stem cell markers have been identified, which enabled detailed characterization of pancreatic cancer stem cells. Recent researches clarified that conventional chemotherapy itself could increase cancer cells with stem cell-phenotype, suggesting the necessity of cancer stem cell-targeting therapy. Based on these observations, pancreatic cancer stem cell-targeting therapies have been tested, which effectively eliminated cancer stem cell fraction and attenuated cancer progression in experimental models. Clinical efficacy of these therapies need to be evaluated, and cancer stem cell-targeting therapy will contribute to improve the prognosis of pancreatic cancer.

  7. Beer and its Non-Alcoholic Compounds: Role in Pancreatic Exocrine Secretion, Alcoholic Pancreatitis and Pancreatic Carcinoma

    PubMed Central

    Gerloff, Andreas; Singer, Manfred V; Feick, Peter

    2010-01-01

    In this article we provide an overview of the newest data concerning the effect of non-alcoholic constituents of alcoholic beverages, especially of beer, on pancreatic secretion, and their possible role in alcoholic pancreatitis and pancreatic carcinoma. The data indicate that non-alcoholic constituents of beer stimulate pancreatic enzyme secretion in humans and rats, at least in part, by direct action on pancreatic acinar cells. Some non-alcoholic compounds of beer, such as quercetin, resveratrol, ellagic acid or catechins, have been shown to be protective against experimentally induced pancreatitis by inhibiting pancreatic secretion, stellate cell activation or by reducing oxidative stress. Quercetin, ellagic acid and resveratrol also show anti-carcinogenic potential in vitro and in vivo. However, beer contains many more non-alcoholic ingredients. Their relevance in beer-induced functional alterations of pancreatic cells leading to pancreatitis and pancreatic cancer in humans needs to be further evaluated. PMID:20617020

  8. What's New in Pancreatic Cancer Research and Treatment?

    MedlinePlus

    ... Cancer Research? Pancreatic Cancer About Pancreatic Cancer What’s New in Pancreatic Cancer Research? Research into the causes , ... KRAS oncogene, which affects regulation of cell growth. New diagnostic tests are often able to recognize this ...

  9. Test-Wiseness: A Cognitive Function?

    ERIC Educational Resources Information Center

    Woodley, Katheryn K.

    This paper reports the findings of an attempt to improve test-wiseness (TW) through direct instruction in selected test-taking strategies. TW was defined as "a cognitive function, subject to improvement through both general exposure to a wide variety of test items, and specific training in test-taking skills." The total investigation included:…

  10. [Pancreatic secretion in domestic sprue].

    PubMed

    Otte, M; Thurmayr, G R; Dageförde, J; Thurmayr, R; Forell, M M

    1985-02-15

    Pancreatic function was determined (using the secretin-pancreozymin test) before the use of gluten-free diet in 22 patients with endemic (celiac) sprue. Water and bicarbonate secretion were within normal limits, if anything there was a trend to high-normal values. Remarkable and apparently characteristic for celiac sprue was the only slight contraction of the gallbladder after intravenous injection of submaximal doses of cholecystokinin-pancreozymin (CCK). Secretion of the 3 enzymes amylase, lipase and trypsin was decreased in about one third of cases, the difference relating both to the concentrations and the amount secreted, compared with normal control values was significant (P greater than 0.01). But in no case was the reduced enzyme secretion so marked that one would expect maldigestion. Multivariate non-linear discriminance analysis demonstrated that pancreatic secretion in sprue is quite distinct from that in healthy subjects and those with chronic pancreatitis. It is assumed that there is a pattern of exocrine pancreatic secretion typical for sprue.

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

    PubMed

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

    2015-11-01

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

  12. 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.

  13. Pancreatic cancer

    MedlinePlus

    ... cancer, cystic pancreatic neoplasms, and other nonendocrine pancreatic tumors. In: Feldman M, Friedman LS, Brandt LJ, ... by: Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital, Boston, MA. ...

  14. Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass.

    PubMed

    Esterházy, Daria; Stützer, Ina; Wang, Haiyan; Rechsteiner, Markus P; Beauchamp, Jeremy; Döbeli, Heinz; Hilpert, Hans; Matile, Hugues; Prummer, Michael; Schmidt, Alexander; Lieske, Nora; Boehm, Bernhard; Marselli, Lorella; Bosco, Domenico; Kerr-Conte, Julie; Aebersold, Ruedi; Spinas, Giatgen Andreia; Moch, Holger; Migliorini, Cristiano; Stoffel, Markus

    2011-09-07

    Decreased β cell mass and function are hallmarks of type 2 diabetes. Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human β cells. Mice with functionally inactive Bace2 and insulin-resistant mice treated with a newly identified Bace2 inhibitor both display augmented β cell mass and improved control of glucose homeostasis due to increased insulin levels. These results implicate Bace2 in the control of β cell maintenance and provide a rational strategy to inhibit this protease for the expansion of functional pancreatic β cell mass.

  15. Enzyme-linked PNA lectin binding assay compared with CA19-9 and CEA radioimmunoassay as a diagnostic blood test for pancreatic cancer.

    PubMed Central

    Ching, C. K.; Rhodes, J. M.

    1989-01-01

    Previous studies have shown that sera from patients with pancreatic cancer often contain a mucus glycoprotein that expresses the oncofetal antigen galactose 1-3, N-acetyl galactosamine, which is the T blood group antigen and the binding site for the lectin peanut agglutinin (PNA). An enzyme-linked lectin assay has been developed to quantify PNA-binding glycoproteins in serum and has been evaluated as a serological test for pancreatic cancer. Sera were studied from 53 patients with pancreatic cancer and 154 controls, including benign obstructive jaundice, acute and chronic pancreatitis, chronic liver disease and inflammatory bowel disease. The enzyme-linked peanut lectin assay proved highly reproducible and has 77% sensitivity and 83% specificity for pancreatic cancer, results that are very similar to those achieved in the same sera by CA19-9 radioimmunoassay (75% sensitivity, 82% specificity with the upper limit of normal set at 37 u ml-1). CEA assay proved less useful (60% sensitivity, 47% specificity). In this study better results were obtained if an upper limit of normal of 50 u ml-1 was used for CA19-9 (75% sensitivity, 92% specificity). Combination of CA19-9 assay with the upper limit set at 50 u ml-1 and the peanut lectin assay improved the sensitivity to 85% with only a slight fall in specificity (85%). These results compare well with published results for ultrasound and CT scanning. PMID:2736232

  16. 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.

  17. PKD signaling and pancreatitis

    PubMed Central

    Yuan, Jingzhen; Pandol, Stephen J.

    2016-01-01

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

  18. 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.

  19. 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

  20. Simultaneous pancreatic-renal transplant scintigraphy

    SciTech Connect

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

    1986-12-01

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

  1. 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

  2. The Full Function Test Explosive Generator

    SciTech Connect

    Reisman, D B; Javedani, J B; Griffith, L V; Ellsworth, G F; Kuklo, R M; Goerz, D A; White, A D; Tallerico, L J; Gidding, D A; Murphy, M J; Chase, J B

    2009-12-13

    We have conducted three tests of a new pulsed power device called the Full Function Test (FFT). These tests represented the culmination of an effort to establish a high energy pulsed power capability based on high explosive pulsed power (HEPP) technology. This involved an extensive computational modeling, engineering, fabrication, and fielding effort. The experiments were highly successful and a new US record for magnetic energy was obtained.

  3. CCD Multi-Function Processor Test Bed.

    DTIC Science & Technology

    1982-01-01

    AD-A111 335 MITRE CORP BEDFORDMA F/6 9/5 CCD MULTIFUNCTION PROCESSOR TEST BED.(U) JAN 82 M W PACZAN. S M WALOSTEIN F19628-81-C-OO01 UNCLASSIFIED MTR...HAIAf III 4 ESD-TR-81-394 MTR-8417 CCD MULTI-FUNCTION PROCESSOR TEST BED By M. W. Paczan and S. M. Waldstein JANUARY 1982 Prepared for DEPUTY FOR...TITLE (and Subtitle) 5. TYPE OF REPORT & PERIOD COVERED CCD MULTI-FUNCTION PROCESSOR TEST BED 6. PERFORMING ORG. REPORT NUMBER MTR-8417 7 AUT-OR(s) S

  4. 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)

  5. Direct comparison of Cryotop(®) vitrification and Bicell(®) freezing on recovery of functional rat pancreatic islets.

    PubMed

    Yamanaka, Takahiro; Tashima, Kazuya; Takahashi, Rio; Takashima, Seiji; Goto, Teppei; Hirabayashi, Masumi; Hochi, Shinichi

    2016-12-01

    Two protocols, Bicell(®) freeze-thawing and Cryotop(®) vitrification-warming, were compared for suitability in cryopreserving rat pancreatic islets (101-150 μm in mean diameter). Immediate survival rates of post-thaw and post-warm islets (50 and 57%, respectively), assessed by FDA/PI double staining, were lower than that of fresh control islets (90%). Most of the PI-positive dead cells were detected in peripheral area of post-warm islets, and were removed after subsequent 24 h culture (survival rate; 85% vs 59% in post-thaw islets). Quantitative PCR analysis showed that Bicell(®) freeze-thawing compromised expression of genes relating to β-cell function (Pdx1 and Glut2), but not to one of apoptotic pathways (Bax/Bcl2 ratio). Expression of these genes was maintained in islets before and after the Cryotop(®) vitrification-warming. Values of stimulus index (SI) for 20 mM/3 mM glucose-stimulated insulin secretion were 6.7, 1.9 and 3.9 in fresh control, post-thaw and post-warm islets, respectively. The SI values after 24 h culture were 4.1, 1.9 and 3.1, respectively. Larger islets (>150 μm in diameter) had comparable survival rates, but lower SI values after Cryotop(®) vitrification-warming when compared to smaller counterparts. These results suggest that rat pancreatic islets can be cryopreserved by Cryotop(®) vitrification-warming rather than Bicell(®) freeze-thawing, without considerable loss of in vitro β-cell function.

  6. Bisphenol A Is More Potent than Phthalate Metabolites in Reducing Pancreatic β-Cell Function

    PubMed Central

    Weldingh, Nina Mickelson; Jørgensen-Kaur, Lena; Holme, Jørn A.

    2017-01-01

    Bisphenol A (BPA) and phthalates are common environmental contaminants that have been proposed to influence incidence and development of types 1 and 2 diabetes. Thus, effects of BPA and three phthalate metabolites (monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP)) were studied in the pancreatic β-cell line INS-1E, after 2–72 h of exposure to 5–500 μM. Three endpoints relevant to accelerated development of types 1 or 2 diabetes were investigated: β-cell viability, glucose-induced insulin secretion, and β-cell susceptibility to cytokine-induced cell death. BPA and the phthalate metabolites reduced cellular viability after 72 h of exposure, with BPA as the most potent chemical. Moreover, BPA, MEHP, and MnBP increased insulin secretion after 2 h of simultaneous exposure to chemicals and glucose, with potency BPA > MEHP > MnBP. Longer chemical exposures (24–72 h) showed no consistent effects on glucose-induced insulin secretion, and none of the environmental chemicals affected susceptibility to cytokine-induced cell death. Overall, BPA was more potent than the investigated phthalate metabolites in affecting insulin secretion and viability in the INS-1E pancreatic β-cells. In contrast to recent literature, concentrations with relevance to human exposures (1–500 nM) did not affect the investigated endpoints, suggesting that this experimental model displayed relatively low sensitivity to environmental chemical exposure. PMID:28286763

  7. Evidence that the oral glucose-tolerance test does not provide a uniform stimulus to pancreatic islets in pregnancy.

    PubMed

    de Leacy, E A; Cowley, D M

    1989-07-01

    Fifty consecutive pregnant patients referred for a glucose-tolerance test were classified on the basis of increasing (n = 20) or decreasing (n = 28) hematocrit after an oral 75-g glucose load. (The hematocrit did not change in the other two patients.) Patients with increasing hematocrit, a response previously seen in patients with the dumping syndrome, showed significantly flatter increases in glucose concentrations in plasma after the load. The mean decrease in the concentration of phosphate in plasma, measured as an index of glucose uptake by cells, was significantly less (P less than 0.05) 2 h after the load in the group with flatter glucose responses, suggesting that the flat response is ascribable to poor glucose absorption rather than to an exaggerated insulin response. These results indicate that the oral glucose-tolerance test stresses the pancreatic islets differently in different pregnant subjects, owing to individual variations in the gastrointestinal handling of the glucose load. Consequently, patients may give a "normal" result who might otherwise become hyperglycemic after normal meals. We suggest that alternative screening procedures be investigated to assess pregnant patients postprandially.

  8. Development of bioluminescent chick chorioallantoic membrane (CAM) models for primary pancreatic cancer cells: a platform for drug testing

    PubMed Central

    Rovithi, Maria; Avan, Amir; Funel, Niccola; Leon, Leticia G.; Gomez, Valentina E.; Wurdinger, Thomas; Griffioen, Arjan W.; Verheul, Henk M. W.; Giovannetti, Elisa

    2017-01-01

    The aim of the present study was to develop chick-embryo chorioallantoic membrane (CAM) bioluminescent tumor models employing low passage cell cultures obtained from primary pancreatic ductal adenocarcinoma (PDAC) cells. Primary PDAC cells transduced with lentivirus expressing Firefly-luciferase (Fluc) were established and inoculated onto the CAM membrane, with >80% engraftment. Fluc signal reliably correlated with tumor growth. Tumor features were evaluated by immunohistochemistry and genetic analyses, including analysis of mutations and mRNA expression of PDAC pivotal genes, as well as microRNA (miRNA) profiling. These studies showed that CAM tumors had histopathological and genetic characteristic comparable to the original tumors. We subsequently tested the modulation of key miRNAs and the activity of gemcitabine and crizotinib on CAM tumors, showing that combination treatment resulted in 63% inhibition of tumor growth as compared to control (p < 0.01). These results were associated with reduced expression of miR-21 and increased expression of miR-155. Our study provides the first evidence that transduced primary PDAC cells can form tumors on the CAM, retaining several histopathological and (epi)genetic characteristics of original tumors. Moreover, our results support the use of these models for drug testing, providing insights on molecular mechanisms underlying antitumor activity of new drugs/combinations. PMID:28304379

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  11. 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.

  12. 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.

  13. Pancreatic Steatosis and Its Relationship to β-Cell Dysfunction in Humans

    PubMed Central

    Szczepaniak, Lidia S.; Victor, Ronald G.; Mathur, Ruchi; Nelson, Michael D.; Szczepaniak, Edward W.; Tyer, Nicole; Chen, Ida; Unger, Roger H.; Bergman, Richard N.; Lingvay, Ildiko

    2012-01-01

    OBJECTIVE To evaluate racial/ethnic differences in pancreatic triglyceride (TG) levels and their relationship to β-cell dysfunction in humans. RESEARCH DESIGN AND METHODS We studied black, Hispanic, and white adults who completed three research visits: screening and an oral glucose tolerance test; frequently sampled intravenous glucose tolerance tests for evaluation of β-cell function and insulin resistance; and proton magnetic resonance spectroscopy for evaluation of pancreatic and hepatic TG levels. RESULTS Pancreatic TG levels were higher in Hispanics and whites than in blacks (P = 0.006). Hepatic TG levels were highest in Hispanics (P = 0.004). Compensatory insulin secretion and disposition index were higher in blacks (P = 0.003 and P = 0.024, respectively). Insulin sensitivity was comparable between Hispanics and blacks and was lower than in whites (P = 0.005). In blacks, compensatory insulin secretion increased steeply with small increments in pancreatic TG levels (R2 = 0.45, slope = 247). In whites, the range of pancreatic TG levels was higher, and the slope was less steep than in blacks (R2 = 0.27, slope = 27). In Hispanics, pancreatic TG levels were similar to those of whites, but compensatory insulin secretion was described by a combination of pancreatic and hepatic TG levels and visceral fat mass ( R2 = 0.32). CONCLUSIONS In a multiethnic sample of adults with mild obesity and without diabetes, we found striking ethnic differences in the levels of pancreatic TGs and in the relationship between pancreatic TGs and β-cell dysfunction. Our data implicate pancreatic TG content measured by proton magnetic resonance spectroscopy as a noninvasive novel biomarker for pancreatic β-cell dysfunction, especially in the Hispanic population. PMID:22968187

  14. Modifications of the Test Information Function.

    ERIC Educational Resources Information Center

    Samejima, Fumiko

    Two modification formulas are presented for the test information function in order to provide better measures of local accuracies of the estimation of "theta" when maximum likelihood estimation is used to provide the estimate of ability "theta." A minimum bound of any estimator, biased or unbiased, is considered; and Formula 1…

  15. Porcine pancreatic alpha-amylase hydrolysis of native starch granules as a function of granule surface area.

    PubMed

    Kong, Byoung-Wook; Kim, Jung-In; Kim, Myo-Jeong; Kim, Jae Cherl

    2003-01-01

    Porcine pancreatic alpha-amylase activity on native starch granules is more accurately described as a function of surface area of the granules rather than of substrate concentration. The apparent K(m) of alpha-amylolysis of native starch from potato, maize, and rice expressed as a function of substrate concentration was largest for potato with a single value of V(max). However, the ratio of the slope of a Lineweaver-Burk plot to that of rice for enzymatic hydrolysis of native potato and maize starch were 7.78 and 2.58, respectively, which were very close to the ratio of surface area per mass of the two starch granules to that of rice. Therefore, the reciprocal of initial velocity was a linear function of the reciprocal of surface area for each starch granule. Surface area was calculated assuming the starch granules were spherical. The values obtained by this calculation were in good agreement with the value obtained by the photomicrographic method. By comparing enzymatic digestion of native maize granules to that of rice granules, it was concluded that the presence of pores in maize granules appeared to significantly affect overall rate of digestion after sufficient reaction time, but not at the very initial stage of hydrolysis.

  16. Lysophosphatidic acid signaling via LPA1 and LPA3 regulates cellular functions during tumor progression in pancreatic cancer cells.

    PubMed

    Fukushima, Kaori; Takahashi, Kaede; Yamasaki, Eri; Onishi, Yuka; Fukushima, Nobuyuki; Honoki, Kanya; Tsujiuchi, Toshifumi

    2017-03-01

    Lysophosphatidic acid (LPA) signaling via G protein-coupled LPA receptors exhibits a variety of biological effects, such as cell proliferation, motility and differentiation. The aim of this study was to evaluate the roles of LPA1 and LPA3 in cellular functions during tumor progression in pancreatic cancer cells. LPA1 and LPA3 knockdown cells were generated from PANC-1 cells. The cell motile and invasive activities of PANC-1 cells were inhibited by LPA1 and LPA3 knockdown. In gelatin zymography, LPA1 and LPA3 knockdown cells indicated the low activation of matrix metalloproteinase-2 (MMP-2) in the presence of LPA. Next, to assess whether LPA1 and LPA3 regulate cellular functions induced by anticancer drug, PANC-1 cells were treated with cisplatin (CDDP) for approximately 6 months. The cell motile and invasive activities of long-term CDDP treated cells were markedly higher than those of PANC-1 cells, correlating with the expression levels of LPAR1 and LPAR3 genes. In soft agar assay, the long-term CDDP treated cells formed markedly large sized colonies. In addition, the cell motile and invasive activities enhanced by CDDP were significantly suppressed by LPA1 and LPA3 knockdown as well as colony formation. These results suggest that LPA signaling via LPA1 and LPA3 play an important role in the regulation of cellular functions during tumor progression in PANC-1 cells.

  17. 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

  18. 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.

  19. Effects of acute exercise on pancreatic endocrine function in subjects with type 2 diabetes.

    PubMed

    Knudsen, S H; Karstoft, K; Winding, K; Holst, J J; Pedersen, B K; Solomon, T P J

    2015-02-01

    We determined the effects of exercise on pancreatic endocrine responses to metabolic stimuli in subjects with type 2 diabetes (T2D) and examined the influence of subjects' diabetic status. Fourteen subjects underwent a hyperglycaemic clamp with glucagon-like peptide-1 (GLP-1) infusion and arginine injection, the morning after a 1-h walk or no exercise. Subjects were stratified by high and low fasting plasma glucose (FPG) levels and by glycated haemoglobin (HbA1c) levels, as well as by current use/non-use of antidiabetic medication. In the entire cohort, exercise did not alter insulin secretion, while glucagon levels were increased in all clamp phases (p < 0.05 to <0.01). In subjects with low FPG levels, exercise increased GLP-1-stimulated insulin secretion (p < 0.05), with the same trend being observed for arginine (p = 0.08). The same trends were seen for subjects with low HbA1c levels. Furthermore, exercise increased GLP-1- and arginine-stimulated insulin secretion (p < 0.05) in subjects who were antidiabetic drug-naïve. Exercise-induced increases in insulin secretion are blunted in subjects with T2D with high rates of hyperglycaemia and in those using antidiabetic drugs.

  20. Size-based separation and collection of mouse pancreatic islets for functional analysis.

    PubMed

    Nam, Ki-Hwan; Yong, Wang; Harvat, Tricia; Adewola, Adeola; Wang, Shesun; Oberholzer, Jose; Eddington, David T

    2010-10-01

    Islet size has recently been demonstrated to be an important factor in determining human islet transplantation outcomes. In this study, a multi-layered microfluidic device was developed and quantified for size-based separation of a heterogeneous population of mouse islets. The device was fabricated using standard soft lithography and polydimethylsiloxane (PDMS). Size-based separation was first demonstrated via injection of a heterogeneous population of glass beads between 50-300 microm in diameter which were separated into five sub-populations based on their diameter. Next, a heterogeneous population of mouse pancreatic islets, between 50-250 microm in diameter was separated into four sub-populations. Throughout this process the islets remained intact without any signs of damage, as indicated by cell viability staining. Islet glucose-stimulated insulin secretion of each sub-population of islets was also evaluated demonstrating that islets smaller than 150 microm have superior stimulation indexes (SI) compared to islets larger than 150 microm. In this study, we found that islets between 100 microm and 150 microm in diameter had the greatest SI value in a heterogeneous population of islets.

  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. Immunological and Functional Characterization of RhoGDI3 and Its Molecular Targets RhoG and RhoB in Human Pancreatic Cancerous and Normal Cells.

    PubMed

    de León-Bautista, Mercedes Piedad; Cardenas-Aguayo, Maria Del Carmen; Casique-Aguirre, Diana; Almaraz-Salinas, Manuel; Parraguirre-Martinez, Sara; Olivo-Diaz, Angelica; Thompson-Bonilla, María Del Rocío; Vargas, Miguel

    2016-01-01

    RhoGDI proteins have been implicated in several human cancers; changes in their expression levels have shown pro- or anti-tumorigenic effects. Pancreatic Ductal Adenocarcinoma (PDAC) is a complex pathology, with poor prognosis, and most patients die shortly after diagnosis. Efforts have been focused on understanding the role of RhoGDI's in PDAC, specially, RhoGDI1 and RhoGDI2. However, the role of RhoGDI3 has not been studied in relation to cancer or to PDAC. Here, we characterized the expression and functionality of RhoGDI3 and its target GTPases, RhoG and RhoB in pancreatic cell lines from both normal pancreatic tissue and tissue in late stages of PDAC, and compared them to human biopsies. Through immunofluorescences, pulldown assays and subcellular fractionation, we found a reduction in RhoGDI3 expression in the late stages of PDAC, and this reduction correlates with tumor progression and aggressiveness. Despite the reduction in the expression of RhoGDI3 in PDAC, we found that RhoB was underexpressed while RhoG was overexpressed, suggesting that cancerous cells preserve their capacity to activate this pathway, thus these cells may be more eager to response to the stimuli needed to proliferate and become invasive unlike normal cells. Surprisingly, we found nuclear localization of RhoGDI3 in non-cancerous pancreatic cell line and normal pancreatic tissue biopsies, which could open the possibility of novel nuclear functions for this protein, impacting gene expression regulation and cellular homeostasis.

  3. Immunological and Functional Characterization of RhoGDI3 and Its Molecular Targets RhoG and RhoB in Human Pancreatic Cancerous and Normal Cells

    PubMed Central

    de León-Bautista, Mercedes Piedad; Cardenas-Aguayo, Maria del Carmen; Casique-Aguirre, Diana; Almaraz-Salinas, Manuel; Parraguirre-Martinez, Sara; Olivo-Diaz, Angelica; Thompson-Bonilla, María del Rocío

    2016-01-01

    RhoGDI proteins have been implicated in several human cancers; changes in their expression levels have shown pro- or anti-tumorigenic effects. Pancreatic Ductal Adenocarcinoma (PDAC) is a complex pathology, with poor prognosis, and most patients die shortly after diagnosis. Efforts have been focused on understanding the role of RhoGDI's in PDAC, specially, RhoGDI1 and RhoGDI2. However, the role of RhoGDI3 has not been studied in relation to cancer or to PDAC. Here, we characterized the expression and functionality of RhoGDI3 and its target GTPases, RhoG and RhoB in pancreatic cell lines from both normal pancreatic tissue and tissue in late stages of PDAC, and compared them to human biopsies. Through immunofluorescences, pulldown assays and subcellular fractionation, we found a reduction in RhoGDI3 expression in the late stages of PDAC, and this reduction correlates with tumor progression and aggressiveness. Despite the reduction in the expression of RhoGDI3 in PDAC, we found that RhoB was underexpressed while RhoG was overexpressed, suggesting that cancerous cells preserve their capacity to activate this pathway, thus these cells may be more eager to response to the stimuli needed to proliferate and become invasive unlike normal cells. Surprisingly, we found nuclear localization of RhoGDI3 in non-cancerous pancreatic cell line and normal pancreatic tissue biopsies, which could open the possibility of novel nuclear functions for this protein, impacting gene expression regulation and cellular homeostasis. PMID:27832197

  4. Acute and chronic pancreatitis: surgical management.

    PubMed

    Dzakovic, Alexander; Superina, Riccardo

    2012-08-01

    Pancreatitis is becoming increasingly prevalent in children, posing new challenges to pediatric health care providers. Although some general adult treatment paradigms are applicable in the pediatric population, diagnostic workup and surgical management of acute and chronic pancreatitis have to be tailored to anatomic and pathophysiological entities peculiar to children. Nonbiliary causes of acute pancreatitis in children are generally managed nonoperatively with hydration, close biochemical and clinical observation, and early initiation of enteral feeds. Surgical intervention including cholecystectomy or endoscopic retrograde cholangiopancreatography is often required in acute biliary pancreatitis, whereas infected pancreatic necrosis remains a rare absolute indication for pancreatic debridement and drainage via open, laparoscopic, or interventional radiologic procedure. Chronic pancreatitis is characterized by painful irreversible changes of the parenchyma and ducts, which may result in or be caused by inadequate ductal drainage. A variety of surgical procedures providing drainage, denervation, resection, or a combination thereof are well established to relieve pain and preserve pancreatic function.

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

    PubMed Central

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

    2015-01-01

    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

  6. Evaluation of Biochemical Markers Serum Amylase and Serum Lipase for the Assessment of Pancreatic Exocrine Function in Diabetes Mellitus

    PubMed Central

    Iyer, Chandrashekhar M; Madivalar, Mamatha Thimmanna; Wadde, Satish Kishanrao; Howale, Deepak Sadashiv

    2016-01-01

    Introduction Diabetes mellitus (DM), a metabolic disorder characterized by hyperglycaemia, associated with deficiency or resistance to insulin indicates endocrinal abnormality of the pancreas. Amylase and lipase are enzymes secreted by the exocrine portion of the pancreas. Endocrinal derangement observed in diabetes may interfere with the exocrine function of the pancreas. Aim To estimate the levels of fasting blood sugar, serum lipase, serum amylase in patients of type 1 and type 2 DM. Than comparing them with healthy controls and to study the effect of type 1 and type 2 DM on pancreatic exocrine function using serum levels of amylase and lipase as biochemical marker. Materials and Methods This study was conducted at GMERS Medical College and Hospital from Dec 2015 to July 2016. Thirty patients of type 1 DM and 30 patients of type 2 DM, who were already diagnosed and taking treatment, were included in this study. A total number of 30 apparently healthy individuals were recruited as the control group in our study. Fasting venous blood samples were collected from the cases as well as the controls and they were analysed by using semi auto analyser for blood glucose, serum amylase and serum lipase. The results were analysed statistically by using SPSS software. Values were expressed as means ± SD. Results We found statistically significant (p<0.01) low values for serum amylase and serum lipase in patients with type 1 and type 2 DM as compared to healthy controls. Fasting blood sugar was significantly higher in cases as compared to controls. We found negative correlation of fasting blood sugar level with serum amylase and serum lipase and positive correlation of serum amylase with serum lipase in both type 1 and type 2 DM. Conclusion Our study clearly demonstrated that in type 1 and type 2 DM, there was increase in fasting blood sugar with decrease in serum amylase and serum lipase which signifies the derangement of endocrine-exocrine axis of the pancreas. Serum

  7. Duplex ultrasound of the superior mesenteric artery in chronic pancreatitis.

    PubMed

    Hornum, M; Larsen, S; Olsen, O; Pedersen, J F

    2006-10-01

    Blood flow in the superior mesenteric artery (SMA) increases after a meal due to a vasoactive effect of the decomposed food. In exocrine pancreatic insufficiency, the digestion of food is compromised. We used duplex ultrasound to test the hypothesis that blood flow in the SMA after a meal increases less in patients with pancreatic insufficiency than in control persons. We studied 16 patients with chronic pancreatitis, eight of them with exocrine insufficiency, and eight healthy volunteers. The resistive index (RI) in the SMA was determined before and after a liquid meal. The RI reflects the downstream circulatory resistance, giving a precise description of mesenteric hyperaemia. Both groups of patients with chronic pancreatitis unexpectedly had lower fasting RI than controls, 0.818 and 0.815 vs 0.851, p = 0.028 and p = 0.0030, respectively. Postprandialy there was significantly less decrease in RI (less increase in flow) in patients with exocrine insufficiency than in controls, 0.055 vs 0.099, p = 0.0047. There was a significant trend for a less pronounced postprandial decrease in RI with more impaired pancreatic function (p = 0.0036). Our study thus demonstrates a reduced postprandial increase in SMA flow in patients with exocrine pancreatic insufficiency, and suggests an increased fasting SMA flow in chronic pancreatitis. Further studies are needed to evaluate the possible role of the test-meal-induced shift in RI in the SMA and of a lower-than-normal fasting RI in the diagnosis and monitoring of chronic pancreatitis.

  8. Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk

    PubMed Central

    Campa, Daniele; Pastore, Manuela; Gentiluomo, Manuel; Talar-Wojnarowska, Renata; Kupcinskas, Juozas; Malecka-Panas, Ewa; Neoptolemos, John P.; Niesen, Willem; Vodicka, Pavel; Fave, Gianfranco Delle; Bueno-de-Mesquita, H. Bas; Gazouli, Maria; Pacetti, Paola; Di Leo, Milena; Ito, Hidemi; Klüter, Harald; Soucek, Pavel; Corbo, Vincenzo; Yamao, Kenji; Hosono, Satoyo; Kaaks, Rudolf; Vashist, Yogesh; Gioffreda, Domenica; Strobel, Oliver; Shimizu, Yasuhiro; Dijk, Frederike; Andriulli, Angelo; Ivanauskas, Audrius; Bugert, Peter; Tavano, Francesca; Vodickova, Ludmila; Zambon, Carlo Federico; Lovecek, Martin; Landi, Stefano; Key, Timothy J.; Boggi, Ugo; Pezzilli, Raffaele; Jamroziak, Krzysztof; Mohelnikova-Duchonova, Beatrice; Mambrini, Andrea; Bambi, Franco; Busch, Olivier; Pazienza, Valerio; Valente, Roberto; Theodoropoulos, George E.; Hackert, Thilo; Capurso, Gabriele; Cavestro, Giulia Martina; Pasquali, Claudio; Basso, Daniela; Sperti, Cosimo; Matsuo, Keitaro; Büchler, Markus; Khaw, Kay-Tee; Izbicki, Jakob; Costello, Eithne; Katzke, Verena; Michalski, Christoph; Stepien, Anna; Rizzato, Cosmeri; Canzian, Federico

    2016-01-01

    The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development of cancer in various organs. However, association between the common genetic variability in this region and pancreatic cancer risk is not clearly understood. We sought to fill this gap in a case-control study genotyping 13 single nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC) patients and 6,111 controls in the context of the Pancreatic Disease Research (PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was associated with an increased pancreatic cancer risk (ORhet=1.14, 95% CI 1.01-1.27, p=0.026, ORhom=1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant is reported to be a mir-SNP that, by changing the binding site of one or more miRNAs, could influence the normal cell cycle progression and in turn increase PDAC risk. In conclusion, we observed a novel association in a pleiotropic region that has been found to be of key relevance in the susceptibility to various types of cancer and diabetes suggesting that the CDKN2A/B locus could represent a genetic link between diabetes and pancreatic cancer risk. PMID:27486979

  9. Platelet function tests: a comparative review.

    PubMed

    Paniccia, Rita; Priora, Raffaella; Liotta, Agatina Alessandrello; 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.

  10. 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

  11. Functional Performance Testing for Power and Return to Sports

    PubMed Central

    Manske, Robert; Reiman, Michael

    2013-01-01

    Context: Functional performance testing of athletes can determine physical limitations that may affect sporting activities. Optimal functional performance testing simulates the athlete’s activity. Evidence Acquisition: A Medline search from 1960 to 2012 was implemented with the keywords functional testing, functional impairment testing, and functional performance testing in the English language. Each author also undertook independent searches of article references. Conclusion: Functional performance tests can bridge the gap between general physical tests and full, unrestricted athletic activity. PMID:24427396

  12. The effects of cisplatin and other divalent platinum compounds on glucose metabolism and pancreatic endocrine function.

    PubMed

    Goldstein, R S; Mayor, G H; Gingerich, R L; Hook, J B; Rosenbaum, R W; Bond, J T

    1983-07-01

    Three divalent platinum compounds, cis-dichlorodiammineplatinum (cis-DDP), trans-dichlorodiammineplatinum (trans-DDP), and ammonium tetrachloroplatinate, were examined for their effects on glucose metabolism in male F-344 rats. Rats were treated with a single iv dose of cis-DDP (0, 2.5, or 5 mg/kg), trans-DDP (0, 5, 7.5, or 15 mg/kg) or tetrachloroplatinate (0, 6, or 18 mg/kg). Glucose tolerance was evaluated 2, 4, 7, and 14 days following platinum treatment by serially measuring plasma glucose before and following an ip glucose load. Administration of 5 mg/kg cis-DDP impaired glucose tolerance on Days 2 and 4, but not on Days 7 and 14. Plasma immunoreactive glucagon (IRG) was elevated at all times following cis-DDP treatment and thus was not correlated with the transient impairment in glucose tolerance. Plasma immunoreactive insulin (IRI) response to a glucose load was deficient relative to the degree of hyperglycemia in cis-DDP-treated (5 mg/kg) animals on Days 2 and 4. However, neither histopathological damage of the pancreas nor pancreatic stores of IRI were affected by cis-DDP treatment. In contrast to cis-DDP, equimolar or greater than equimolar doses of trans-DDP or tetrachloroplatinate did not significantly affect glucose tolerance at any time examined. These results indicate that cis-DDP-mediated glucose intolerance is unique to the geometry of the complex and is related to properties other than the presence of a divalent platinum atom. Furthermore, glucose intolerance following cis-DDP treatment appears to be related to a relative deficiency in insulin secretion.

  13. Siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes

    PubMed Central

    Dharmadhikari, Gitanjali; Stolz, Katharina; Hauke, Michael; Morgan, Noel G.; Varki, Ajit; de Koning, Eelco; Kelm, Sørge; Maedler, Kathrin

    2017-01-01

    Chronic inflammation plays a key role in both type 1 and type 2 diabetes. Cytokine and chemokine production within the islets in a diabetic milieu results in β-cell failure and diabetes progression. Identification of targets, which both prevent macrophage activation and infiltration into islets and restore β-cell functionality is essential for effective diabetes therapy. We report that certain Sialic-acid-binding immunoglobulin-like-lectins (siglecs) are expressed in human pancreatic islets in a cell-type specific manner. Siglec-7 was expressed on β-cells and down-regulated in type 1 and type 2 diabetes and in infiltrating activated immune cells. Over-expression of Siglec-7 in diabetic islets reduced cytokines, prevented β-cell dysfunction and apoptosis and reduced recruiting of migrating monocytes. Our data suggest that restoration of human Siglec-7 expression may be a novel therapeutic strategy targeted to both inhibition of immune activation and preservation of β-cell function and survival. PMID:28378743

  14. Chlordiazepoxide (Librium) and Tests of Thyroid Function

    PubMed Central

    Clark, Frederick; Hall, Reginald

    1970-01-01

    The effect of chlordiazepoxide (Librium) on thyroid function was examined in 14 euthyroid patients who required the drug for psychiatric reasons and in six patients with clinically mild thyrotoxicosis. There was no significant difference in results from tests of thyroid iodide trapping (thyroid radioiodine uptake, thyroid clearance, and absolute iodine uptake) or of thyroid hormone release (protein-bound iodine, T3 resin uptake, and free thyroxine index) carried out before and during treatment with the drug over a four-week period. It is suggested that chlordiazepoxide need not be withdrawn before thyroid status and function are assessed in any patient taking the drug. PMID:4192645

  15. [Cardiology. Platelet function testing for clinicians].

    PubMed

    Pellaton, Cyril; Eeckhout, Eric; Silvain, Johanne; Montalescot, Gilles; Collet, Jean-Phillipe

    2014-01-15

    Platelet P2YI2 receptor inhibition with clopidogrel, prasugrel or ticagrelor plays a key role to prevent recurrent ischaemic events after percutaneous coronary intervention in acute coronary syndromes or elective settings. The degree of platelet inhibition depends on the antiplatelet medication used and is influenced by clinical and genetic factors. A concept of therapeutic window exists. On one side, efficient anti-aggregation is required in order to reduce cardio-vascular events. On the other side, an excessive platelet inhibition represents a risk of bleeding complications. This article describes the current knowledge about some platelet function tests and genetic tests and summarises their role in the clinical practice.

  16. 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

  17. Improvement of isolated rat pancreatic islets function by combination of cerium oxide nanoparticles/sodium selenite through reduction of oxidative stress.

    PubMed

    Pourkhalili, Nazila; Hosseini, Asieh; Nili-Ahmadabadi, Amir; Rahimifard, Mahban; Navaei-Nigjeh, Mona; Hassani, Shokoufeh; Baeeri, Maryam; Abdollahi, Mohammad

    2012-07-01

    Insulin Dependent Diabetes Mellitus (IDDM) is a disease with high incidence with no pure cure therapy yet. In most of cases, these patients need pancreatic islets transplantation that is not completely successful because of oxidative stress happening during isolation and transplantation procedures. In the present study, effective factors in transplantation procedure such as viability, insulin secretion, production of reactive oxygen molecules (ROM), and mitochondrial energy as ATP/ADP ratio were examined in the isolated islets exposed to sodium selenite (Na₂SeO₃; 0 30 nmol/L), metal form of cerium oxide (100 nm), cerium oxide nanoparticles (100 nm) and combination of Na₂SeO₃ (30 nmol/L)/cerium oxide nanoparticles (100 nm) in a time course (1, 2, 4 and 6 days posttreatment) manner. The results showed a significant increase of cells viability, secretion of insulin, and ATP/ADP ratio and a reduction in ROM by use of sodium selenite, cerium oxide nanoparticles, and especially combination of cerium oxide nanoparticles/sodium selenite. Interestingly, not only no improvement was found with metal form of cerium oxide but also deterioration occurred in tested markers. Results suggest that pretreatment with combination of cerium oxide nanoparticles/sodium selenite can improve transplantation outcome and graft function by control of oxidative stress damage.

  18. Pulmonary function testing in asthma: nursing applications.

    PubMed

    Conner, Brenda; Meng, Anne

    2003-12-01

    Spirometry has become the most widely used assessment of pulmonary function for diagnostic and prognostic purposes. This article reviews the indications for spirometry in persons who have asthma, the parameters measured, acceptable testing techniques, acceptability, quality assurance criteria, and basic interpretation of results in evaluating the person who has asthma. Understanding basic spirometry is an invaluable aid to the nurse and nurse practitioner who provide care to children and adults who have asthma.

  19. 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

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

    SciTech Connect

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

    2007-02-15

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

  1. SIRT1 promotes the proliferation and metastasis of human pancreatic cancer cells.

    PubMed

    Jin, Jianguang; Chu, Zhijie; Ma, Pengfei; Meng, Yuanpu; Yang, Yanhui

    2017-03-01

    SIRT1 plays an important role in human malignant progression, inducing cancer cell proliferation and metastasis by regulating downstream gene expressions. However, little is known about the underlying mechanisms in which SIRT1 promotes pancreatic cancer tumorigenesis. The aim of this study is to investigate the SIRT1 expression levels and biological functions in promoting pancreatic cancer progression. We first investigated the expression of SIRT1 in a series of pancreatic cancer tissues as well as in a panel of pancreatic cancer cell lines. The effect of SIRT1 on cell activity was explored by knockdown experiments. Cell growth was measured using the MTT assay and colony-formation assay. Migration and invasion were tested using transwell assay. Our results showed that the expression of SIRT1 was significantly up-regulated both in pancreatic cancer tissues and cell lines. Knockdown of SIRT1 suppressed cell proliferation and migration of pancreatic cancer cells. This is the first report to disclose the role of SIRT1 in regulation of pancreatic cancer cell proliferation and migration, which may provide a potential therapeutic target for pancreatic cancer patients.

  2. Hydrocarbon exposure, pancreatitis, and bile acids.

    PubMed Central

    Hotz, P; Pilliod, J; Bourgeois, R; Boillat, M A

    1990-01-01

    The data on hydrocarbon induced pancreatitis are conflicting. This question was therefore studied in a non-selected population exposed to hydrocarbons and in "formerly" exposed workers. Neither the past clinical history nor the pancreatic tests provided any evidence for a causal relation between exposure and pancreatitis. No signs of hydrocarbon induced liver damage were seen either. As a healthy worker effect cannot be totally excluded, however, a case-control study in a group of patients suffering from non-alcohol induced pancreatitis could give useful indications for finally excluding the possibility of pancreatitis being induced by hydrocarbons. PMID:2271391

  3. Stimulation of insulin release by phospholipase D. A potential role for endogenous phosphatidic acid in pancreatic islet function.

    PubMed

    Metz, S A; Dunlop, M

    1990-09-01

    Although exogenous phosphatidic acid (PA) has been shown to promote insulin release, the effects of endogenous PA on endocrine function are largely unexplored. In order to generate PA in situ, intact adult-rat islets were treated with exogenous phospholipases of the D type (PLD), and their effects on phospholipid metabolism and on insulin release were studied in parallel. Chromatographically purified PLD from Streptomyces chromofuscus stimulated the accumulation of PA in [14C]arachidonate- or [14C]myristate-prelabelled islets, and also promoted insulin secretion over an identical concentration range. During 30 min incubations, insulin release correlated closely with the accumulation of [14C]arachidonate-labelled PA (r2 = 0.98; P less than 0.01) or [14C]myristate-labelled PA (r2 = 0.97; P less than 0.01). Similar effects were seen both in freshly isolated and in overnight-cultured intact islets. In contrast, PLDs (from cabbage or peanut) which do not support phospholipid hydrolysis at the pH of the extracellular medium also did not promote insulin release. The effects on secretion of the active PLD preparation were inhibited by modest cooling (to 30 degrees C); dantrolene or Co2+ also inhibited PLD-induced secretion without decreasing PLD-induced PA formation. Additionally, the removal of PLD left the subsequent islet responsiveness to glucose intact, further supporting an exocytotic non-toxic mechanism. PLD-induced insulin release did not appear to require influx of extracellular Ca2+, nor could the activation of protein kinase C clearly be implicated. During incubations of 30 min, PLD selectively generated PA; however, more prolonged incubations (60 min) also led to production of some diacyglycerol and free arachidonic acid concomitant with progressive insulin release. These data suggest that PLD activation has both rapid and direct effects (via PA) and more delayed, secondary, effects (via other effects of PA or the generation of other lipid signals). Taken in

  4. Apigenin: Selective CK2 inhibitor increases Ikaros expression and improves T cell homeostasis and function in murine pancreatic cancer

    PubMed Central

    Nelson, Nadine; Szekeres, Karoly; Iclozan, Cristina; Rivera, Ivannie Ortiz; McGill, Andrew; Johnson, Gbemisola; Nwogu, Onyekachi

    2017-01-01

    Pancreatic cancer (PC) evades immune destruction by favoring the development of regulatory T cells (Tregs) that inhibit effector T cells. The transcription factor Ikaros is critical for lymphocyte development, especially T cells. We have previously shown that downregulation of Ikaros occurs as a result of its protein degradation by the ubiquitin-proteasome system in our Panc02 tumor-bearing (TB) mouse model. Mechanistically, we observed a deregulation in the balance between Casein Kinase II (CK2) and protein phosphatase 1 (PP1), which suggested that increased CK2 activity is responsible for regulating Ikaros’ stability in our model. We also showed that this loss of Ikaros expression is associated with a significant decrease in CD4+ and CD8+ T cell percentages but increased CD4+CD25+ Tregs in TB mice. In this study, we evaluated the effects of the dietary flavonoid apigenin (API), on Ikaros expression and T cell immune responses. Treatment of splenocytes from naïve mice with (API) stabilized Ikaros expression and prevented Ikaros downregulation in the presence of murine Panc02 cells in vitro, similar to the proteasome inhibitor MG132. In vivo treatment of TB mice with apigenin (TB-API) improved survival, reduced tumor weights and prevented splenomegaly. API treatment also restored protein expression of some Ikaros isoforms, which may be attributed to its moderate inhibition of CK2 activity from splenocytes of TB-API mice. This partial restoration of Ikaros expression was accompanied by a significant increase in CD4+ and CD8+ T cell percentages and a reduction in Treg percentages in TB-API mice. In addition, CD8+ T cells from TB-API mice produced more IFN-γ and their splenocytes were better able to prime allogeneic CD8+ T cell responses compared to TB mice. These results provide further evidence that Ikaros is regulated by CK2 in our pancreatic cancer model. More importantly, our findings suggest that API may be a possible therapeutic agent for stabilizing Ikaros

  5. 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

  6. [Surgical management of chronic pancreatitis].

    PubMed

    Regimbeau, Jean-Marc; Dumont, Frédéric; Yzet, Thierry; Chatelain, Denis; Bartoli, Eacute Ric; Brazier, Franck; Bréhant, Olivier; Dupas, Jean-Louis; Mauvais, François; Delcenserie, Richard

    2007-01-01

    Surgical indications for chronic pancreatitis can be schematically separated into five main groups: pain, effects of fibrosis on adjacent organs, the consequences of main pancreatic duct rupture above an obstruction, and suspected cancer. Finally surgery is also indicated in patients who cannot undergo endoscopic procedures (no accessible papilla) or who have too recently undergone this procedure. Surgical procedures include derivation (pancreatic, cystic, biliary) or mixed procedures combining derivation/resection or pancreatic resection. Finally splanchnicectomy can be discussed. Whatever the indication, surgical treatment must meet several goals: the approach to surgery must be multidisciplinary, surgery must be associated with low morbidity and mortality, preserve as much endocrine function as possible, improve quality of life, and be evaluated in the long term, as well as prospectively if possible. We clarify some important points about the management of patients with chronic pancreatitis before discussing the various treatments in detail.

  7. [Diabetes mellitus in acute pancreatitis].

    PubMed

    Díaz-Rubio, José Luis; Torre-Delgadillo, Aldo; Robles-Díaz, Guillermo

    2002-01-01

    Exocrine and endocrine components of pancreas are interrelated anatomically and functionally. Exocrine pancreatic dysfunction often accompanies endocrine pancreatic impairment and vice versa. Diabetes mellitus resulting from alterations of exocrine pancreas, such as acute or chronic pancreatitis, is known as pancreatic diabetes. Hyperglycemia during acute pancreatitis (AP) can be due to abnormalities in insulin secretion, increase in counterregulatory hormones release, or decrease in glucose utilization by peripheral tissues. Causal association is suggested between diabetic ketoacidosis and AP and is attributed to alternation in metabolism of triglycerides. High blood glucose levels are associated with severe AP and constitute factor of worst prognosis. Some patients are discharged with diabetes after AP episode, while others develop diabetes during first year of follow-up. Origin and frequency of glycemic abnormalities associated with AP have not been settled yet accurately. Also, predictive factors for diabetes development and persistence after AP have not been recognized to date.

  8. Pancreatic Cysts

    MedlinePlus

    ... fluid can be collected from the cyst for analysis in a laboratory for possible signs of cancer. The characteristics and location of the pancreatic cyst, with your age and sex, can help doctors pinpoint the type of cyst ...

  9. Pancreatic abscess

    MedlinePlus

    ... high. Possible Complications Complications may include: Multiple abscesses Sepsis When to Contact a Medical Professional Call your ... 2016:chap 144. Read More Abscess Pancreatic pseudocyst Sepsis Review Date 10/27/2015 Updated by: Subodh ...

  10. Identification of genetic variants predictive of early onset pancreatic cancer through a population science analysis of functional genomic datasets.

    PubMed

    Chen, Jinyun; Wu, Xifeng; Huang, Yujing; Chen, Wei; Brand, Randall E; Killary, Ann M; Sen, Subrata; Frazier, Marsha L

    2016-08-30

    Biomarkers are critically needed for the early detection of pancreatic cancer (PC) are urgently needed. Our purpose was to identify a panel of genetic variants that, combined, can predict increased risk for early-onset PC and thereby identify individuals who should begin screening at an early age. Previously, we identified genes using a functional genomic approach that were aberrantly expressed in early pathways to PC tumorigenesis. We now report the discovery of single nucleotide polymorphisms (SNPs) in these genes associated with early age at diagnosis of PC using a two-phase study design. In silico and bioinformatics tools were used to examine functional relevance of the identified SNPs. Eight SNPs were consistently associated with age at diagnosis in the discovery phase, validation phase and pooled analysis. Further analysis of the joint effects of these 8 SNPs showed that, compared to participants carrying none of these unfavorable genotypes (median age at PC diagnosis 70 years), those carrying 1-2, 3-4, or 5 or more unfavorable genotypes had median ages at diagnosis of 64, 63, and 62 years, respectively (P = 3.0E-04). A gene-dosage effect was observed, with age at diagnosis inversely related to number of unfavorable genotypes (Ptrend = 1.0E-04). Using bioinformatics tools, we found that all of the 8 SNPs were predicted to play functional roles in the disruption of transcription factor and/or enhancer binding sites and most of them were expression quantitative trait loci (eQTL) of the target genes. The panel of genetic markers identified may serve as susceptibility markers for earlier PC diagnosis.

  11. 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

  12. Testing visual function in the clinical setting.

    PubMed

    Westheimer, Gerald

    2010-07-01

    The explosive growth of automatic examination of the eye, in particular for determining refractive corrections, invites an analysis of the strengths and limitations of these devices and their role in clinical decisions. Subjective refraction procedures are based on a patient's visual responses and these embrace many levels of additional optical and neural processing and factors involving the higher-order nervous system and perception. Because the ultimate mission is the maintenance and improvement of a patient's visual experiences, the optometric examination necessarily extends beyond the employment of automatic devices and therefore, should include engaging the patients in tests of their visual functions.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. Specific transduction and labeling of pancreatic ducts by targeted recombinant viral infusion into mouse pancreatic ducts.

    PubMed

    Guo, Ping; Xiao, Xiangwei; El-Gohary, Yousef; Criscimanna, Angela; Prasadan, Krishna; Rymer, Christopher; Shiota, Chiyo; Wiersch, John; Gaffar, Iliana; Esni, Farzad; Gittes, George K

    2013-11-01

    Specific labeling of pancreatic ducts has proven to be quite difficult. Such labeling has been highly sought after because of the power it would confer to studies of pancreatic ductal carcinogenesis, as well as studies of the source of new insulin-producing β-cells. Cre-loxp recombination could, in theory, lineage-tag pancreatic ducts, but results have been conflicting, mainly due to low labeling efficiencies. Here, we achieved a high pancreatic duct labeling efficiency using a recombinant adeno-associated virus (rAAV) with a duct-specific sox9 promoter infused into the mouse common biliary/pancreatic duct. We saw rapid, diffuse duct-specific labeling, with 50 and 89% labeling in the pancreatic tail and head region, respectively. This highly specific labeling of ducts should greatly enhance our ability to study the role of pancreatic ducts in numerous aspects of pancreatic growth, development and function.

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

    SciTech Connect

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

    2015-08-07

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

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

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

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

  20. 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

  1. 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.

  2. Liver Function Tests Following Open Cardiac Surgery

    PubMed Central

    Sabzi, Feridoun; Faraji, Reza

    2015-01-01

    Introduction: The cardiopulmonary bypass may have multiple systemic effects on the body organs as liver. This prospective study was planned to explore further the incidence and significance of this change. Methods: Two hundred patients with coronary artery bypass grafting (CABG), were randomly selected for the study. Total and indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase were measured preoperatively and at 24, 48 and 72 hours, following coronary artery bypass grafting. Postoperative value of the liver function tests with respect to hypothermia or hypotension were compared by one way analysis of variance for repeated measure and compared with t test. Patient’s characteristics with bilirubin value (≤1.5 mg or >1.5 mg) were compared with t test. Results: A significant increase of total bilirubin, aspartate aminotransferase, and alkaline phosphatase were noted in the third postoperative day. Significant relation was seen between hypotension and alkaline phosphatase, and aspartate aminotransferase change but hypothermia had not affected alanine aminotransferase, total bilirubin and indirect bilirubin change. Pump time, alanine aminotransferase in third postoperative day and direct bilirubin in first and second day of postoperative period had significant relation with pre and post-operative bilirubin change. Conclusion: Transient but not permanent alterations of hepatic enzymes after coronary artery bypass grafting presumably attributed to the decreased hepatic flow, hypoxia, or pump-induced inflammation. PMID:26191391

  3. Diabetic rat testes: morphological and functional alterations.

    PubMed

    Ricci, G; Catizone, A; Esposito, R; Pisanti, F A; Vietri, M T; Galdieri, M

    2009-12-01

    Reproductive dysfunction is a consequence of diabetes, but the underlying mechanisms are poorly understood. This study investigated the histological and molecular alterations in the testes of rats injected with streptozotocin at prepuperal (SPI rats) and adult age (SAI rats) to understand whether diabetes affects testicular tissue with different severity depending on the age in which this pathological condition starts. The testes of diabetic animals showed frequent abnormal histology, and seminiferous epithelium cytoarchitecture appeared altered as well as the occludin distribution pattern. The early occurrence of diabetes increased the percentage of animals with high number of damaged tubules. The interstitial compartment of the testes was clearly hypertrophic in several portions of the organs both in SPI and SAI rats. Interestingly, fully developed Leydig cells were present in all the treated animals although abnormally distributed. Besides the above-described damages, we found a similar decrease in plasma testosterone levels both in SPI and SAI rats. Oxidative stress (OS) is involved in the pathogenesis of various diabetic complications, and in our experimental models we found that manganese superoxide dismutase was reduced in diabetic animals. We conclude that in STZ-induced diabetes, the altered spermatogenesis, more severe in SPI animals, is possibly due to the effect of OS on Leydig cell function which could cause the testosterone decrease responsible for the alterations found in the seminiferous epithelium of diabetic animals.

  4. 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.

  5. 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 Central

    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

  6. Secretin stimulation test (image)

    MedlinePlus

    ... secrete a fluid with a high concentration of bicarbonate. This fluid neutralizes the acidity from the stomach ... pancreas (for example chronic pancreatitis, cystic fibrosis, pancreatic cancer) may have abnormal pancreatic function.

  7. In Vivo Role of Focal Adhesion Kinase in Regulating Pancreatic β-Cell Mass and Function Through Insulin Signaling, Actin Dynamics, and Granule Trafficking

    PubMed Central

    Cai, Erica P.; Casimir, Marina; Schroer, Stephanie A.; Luk, Cynthia T.; Shi, Sally Yu; Choi, Diana; Dai, Xiao Qing; Hajmrle, Catherine; Spigelman, Aliya F.; Zhu, Dan; Gaisano, Herbert Y.; MacDonald, Patrick E.; Woo, Minna

    2012-01-01

    Focal adhesion kinase (FAK) acts as an adaptor at the focal contacts serving as a junction between the extracellular matrix and actin cytoskeleton. Actin dynamics is known as a determinant step in insulin secretion. Additionally, FAK has been shown to regulate insulin signaling. To investigate the essential physiological role of FAK in pancreatic β-cells in vivo, we generated a transgenic mouse model using rat insulin promoter (RIP)–driven Cre-loxP recombination system to specifically delete FAK in pancreatic β-cells. These RIPcre+fakfl/fl mice exhibited glucose intolerance without changes in insulin sensitivity. Reduced β-cell viability and proliferation resulting in decreased β-cell mass was observed in these mice, which was associated with attenuated insulin/Akt (also known as protein kinase B) and extracellular signal–related kinase 1/2 signaling and increased caspase 3 activation. FAK-deficient β-cells exhibited impaired insulin secretion with normal glucose sensing and preserved Ca2+ influx in response to glucose, but a reduced number of docked insulin granules and insulin exocytosis were found, which was associated with a decrease in focal proteins, paxillin and talin, and an impairment in actin depolymerization. This study is the first to show in vivo that FAK is critical for pancreatic β-cell viability and function through regulation in insulin signaling, actin dynamics, and granule trafficking. PMID:22498697

  8. A Test for Measuring Gustatory Function

    PubMed Central

    Smutzer, Gregory; Lam, Si; Hastings, Lloyd; Desai, Hetvi; Abarintos, Ray A.; Sobel, Marc; Sayed, Nabil

    2010-01-01

    Objectives The purpose of this study is to determine the usefulness of edible taste strips for measuring human gustatory function. Research Design The physical properties of edible taste strips were examined in order to determine their potential for delivering threshold and suprathreshold amounts of taste stimuli to the oral cavity. Taste strips were then assayed by fluorescence to analyze the uniformity and distribution of bitter tastant in the strips. Finally, taste recognition thresholds for sweet taste were examined in order to determine whether or not taste strips would produce recognition thresholds that were equal to or better than those obtained from aqueous tests. Methodology Edible strips were prepared from pullulan-hydroxypropyl methylcellulose solutions that were dried to a thin film. The maximal amount of a tastant that could be incorporated in a 2.54 × 2.54 cm taste strip was identified by including representative taste stimuli for each class of tastant (sweet, sour, salty, bitter, and umami) during strip formation. Distribution of the bitter tastant quinine hydrochloride in taste strips was assayed by fluorescence emission spectroscopy. The efficacy of taste strips for evaluating human gustatory function was examined by using a single series ascending method of limits protocol. Sucrose taste recognition threshold data from edible strips was then compared to results that were obtained from a standard “sip and spit” recognition threshold test. Results Edible films that formed from a pullulan-hydroxypropyl methylcellulose polymer mixture can be used to prepare clear, thin strips that have essentially no background taste and leave no physical presence after release of tastant. Edible taste strips could uniformly incorporate up to five percent of their composition as tastant. Taste recognition thresholds for sweet taste were over one order of magnitude lower with edible taste strips when compared to an aqueous taste test. Conclusion Edible taste

  9. [Acute pancreatitis].

    PubMed

    Hecker, M; Mayer, K; Askevold, I; Collet, P; Weigand, M A; Krombach, G A; Padberg, W; Hecker, A

    2014-03-01

    Acute pancreatitis is a potentially fatal disease with individually differing expression of systemic involvement. For this reason early diagnosis with subsequent risk stratification is essential in the clinical management of this frequent gastroenterological disorder. Severe forms of acute pancreatitis occur in approximately 20 % of cases often requiring intensive care monitoring and interdisciplinary therapeutic approaches. In the acute phase adequate fluid replacement and sufficient analgesic therapy is of major therapeutic importance. Concerning the administration of antibiotics and the nutritional support of patients with acute pancreatitis a change in paradigms could be observed in recent years. Furthermore, endoscopic, radiological or surgical interventions can be necessary depending on the severity of the disease and potential complications.

  10. 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.

  11. [The function of the coagulation hemostatic and fibrinolytic processes in the postoperative period in patients with complicated chronic pancreatitis].

    PubMed

    Shishlov, V I

    1999-01-01

    Intravenous infusion of modified amino acid cocktail (AC), based of the "Aminosyn PF" composition with addition of glutamine, methyonine and selenium was applied in the complex of treatment of patients with complicated chronic pancreatitis. After AC infusion during 3 days after the operation the coagulation indexes restoration was noted while after conventional treatment in these terms the signs of thrombohemorrhagic syndrome were registered.

  12. 20 CFR 718.103 - Pulmonary function tests.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., height, and weight of claimant at the time of the test; (3) Name of technician; (4) Name and signature of... 20 Employees' Benefits 4 2014-04-01 2014-04-01 false Pulmonary function tests. 718.103 Section 718... function tests. (a) Any report of pulmonary function tests submitted in connection with a claim...

  13. 20 CFR 718.103 - Pulmonary function tests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Pulmonary function tests. 718.103 Section 718..., height, and weight of claimant at the time of the test; (3) Name of technician; (4) Name and signature of... function tests. (a) Any report of pulmonary function tests submitted in connection with a claim...

  14. Autoimmune pancreatitis mimicking pancreatic tumor

    PubMed Central

    Dede, Kristóf; Salamon, Ferenc; Taller, András; Teknős, Dániel; Bursics, Attila

    2012-01-01

    Autoimmune pancreatitis (AIP) is a rare disease of unknown pathomechanism. It belongs to the IgG4-related disease family and responds well to steroids, although the relapse rate can reach up to 20–30%. Differentiating AIP from the more common pancreatic cancer can be very challenging. About 20% of AIP is diagnosed postoperatively during final histological examination. Each of the investigative tools can add something to the definitive diagnosis; the question remains whether it is possible to prevent an unnecessary resection. Through our case we would like to demonstrate the differential diagnostic opportunities and present the literary background of this issue. In conclusion, we can state that whenever a focal pancreatic lesion is encountered AIP should always be considered. PMID:24968399

  15. Functional imaging of interstitial brachytherapy in pancreatic carcinoma xenografts using spectral CT: how does iodine concentration correlate with standardized uptake value of 18FDG-PET-CT?

    PubMed Central

    Hu, Shudong; Shi, Xiaofeng; Chen, Yerong; Huang, Wei; Song, Qi; Lin, Xiaozhu; Liu, Yu; Chen, Kemin

    2016-01-01

    Objective: This study aimed to investigate the correlation between iodine concentration (IC) for the quantitative analysis of spectral CT and maximum standardized uptake value (SUVmax) of 18 fludeoxyglucose positron emission tomography–CT (18FDG PET–CT) as an indicator of therapeutic response to interstitial brachytherapy in transplanted human pancreatic carcinomas in BALB/c-nu mice. Methods: Xenograft models were created by subcutaneous injection of SW1990 human pancreatic cancer cell suspensions into immunodeficient BALB/c-nu mice. 30 mice bearing SW1990 human pancreatic cancer cell xenografts were randomly separated into two groups: experimental (n = 15; 1.0 mCi) and control (n = 15, 0 mCi). After 2 weeks of treatment, spectral CT and 18FDG micro-PET–CT scan were performed. IC values and SUVmax in the lesions were measured. IC normalized to the muscle tissue is indicated as nIC. The relationships between the nIC and SUVmax of the transplantation tumours were analysed. Results: 2 weeks after treatment, the nIC in three-phase scans and SUVmax of the experimental group were significantly lower than those of the control group. The nIC values of the three-phase scans have certain positive correlation with the SUVmax values (r = 0.69, p < 0.05; r = 0.73 and p < 0.05; r = 0.80, p < 0.05 in the 10-, 25- and 60-s phase, respectively). Conclusion: Spectral CT could serve as a valuable imaging modality, as our results suggest that nIC correlates with SUVmax of 18FDG PET–CT for evaluating the therapeutic effect of 125I interstitial brachytherapy in a pancreatic carcinoma xenograft. Advances in knowledge: Spectral CT offers opportunities to assess the therapeutic response of pancreatic cancer. This study supports the conclusion that nIC values in spectral CT could also serve as a valuable functional imaging parameter for early monitoring and evaluation of the therapeutic response of 125I interstitial brachytherapy mouse models

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

    PubMed Central

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

    2014-01-01

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

  17. Molecular mechanisms of pancreatitis: current opinion.

    PubMed

    Vonlaufen, Alain; Wilson, Jeremy S; Apte, Minoti V

    2008-09-01

    Pancreatitis (necroinflammation of the pancreas) has both acute and chronic manifestations. Gallstones are the major cause of acute pancreatitis, whereas alcohol is associated with acute as well as chronic forms of the disease. Cases of true idiopathic pancreatitis are steadily diminishing as more genetic causes of the disease are discovered. The pathogenesis of acute pancreatitis has been extensively investigated over the past four decades; the general current consensus is that the injury is initiated within pancreatic acinar cells subsequent to premature intracellular activation of digestive enzymes. Repeated attacks of acute pancreatitis have the potential to evolve into chronic disease characterized by fibrosis and loss of pancreatic function. Our knowledge of the process of scarring has advanced considerably with the isolation and study of pancreatic stellate cells, now established as the key cells in pancreatic fibrogenesis. The present review summarizes recent developments in the field particularly with respect to the progress made in unraveling the molecular mechanisms of acute and chronic pancreatic injury secondary to gallstones, alcohol and genetic factors. It is anticipated that continued research in the area will lead to the identification and characterization of molecular pathways that may be therapeutically targeted to prevent/inhibit the initiation and progression of the disease.

  18. Is Pancreatic Cancer Hereditary?

    MedlinePlus

    ... Trials Database Supporting Research Raising Awareness Our Blog Patient Education Pancreas News Basics of Pancreatic Cancer FAQs The ... Detection- Goggins Lab Sol Goldman Center Discussion Board Patient Education / Basics of Pancreatic Cancer Is pancreatic cancer hereditary? ...

  19. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as the sudden inflammation ... the incidence of recurrent attacks minimized. Timothy Gardner, MD is Director of Pancreatic Disorders at Dartmouth-Hitchcock ...

  20. 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

  1. 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

  2. Screening Test Items for Differential Item Functioning

    ERIC Educational Resources Information Center

    Longford, Nicholas T.

    2014-01-01

    A method for medical screening is adapted to differential item functioning (DIF). Its essential elements are explicit declarations of the level of DIF that is acceptable and of the loss function that quantifies the consequences of the two kinds of inappropriate classification of an item. Instead of a single level and a single function, sets of…

  3. Models of acute and chronic pancreatitis.

    PubMed

    Lerch, Markus M; Gorelick, Fred S

    2013-06-01

    Animal models of acute and chronic pancreatitis have been created to examine mechanisms of pathogenesis, test therapeutic interventions, and study the influence of inflammation on the development of pancreatic cancer. In vitro models can be used to study early stage, short-term processes that involve acinar cell responses. Rodent models reproducibly develop mild or severe disease. One of the most commonly used pancreatitis models is created by administration of supraphysiologic concentrations of caerulein, an ortholog of cholecystokinin. Induction of chronic pancreatitis with factors thought to have a role in human disease, such as combinations of lipopolysaccharide and chronic ethanol feeding, might be relevant to human disease. Models of autoimmune chronic pancreatitis have also been developed. Most models, particularly of chronic pancreatitis, require further characterization to determine which features of human disease they include.

  4. The role of pancreatic ducts in the pathogenesis of acute pancreatitis.

    PubMed

    Hegyi, Peter; Rakonczay, Zoltan

    2015-07-01

    Pancreatic ducts secrete 2.5 l of alkaline, HCO3(-)-rich fluid daily which greatly contributes to the homeostasis of the pancreas. Ducts are also important in the pathophysiology of the pancreas; alteration of ductal function can lead to severe diseases such as cystic fibrosis and chronic pancreatitis. The role of pancreatic ducts in the development of acute pancreatitis has only been uncovered recently. Pancreatitis inducing agents like bile acids and ethanol dose-dependently affect pancreatic ductal secretion; low concentrations stimulate, whereas high concentrations inhibit secretion. The majority of the review will focus on the central role of cystic fibrosis transmembrane conductance regulator (CFTR), a critical protein in the regulation of ductal secretion, in the pathogenesis of acute pancreatitis which is highlighted by numerous investigations. Downregulation of CFTR expression results in increased severity of acute pancreatitis in mice. Furthermore, human genetic studies have demonstrated statistically significant association of CFTR mutations with acute recurrent pancreatitis. Overall, the data support the involvement of pancreatic ducts in the pathogenesis of acute pancreatitis.

  5. [On PACAP-aggravated experimental acute pancreatitis].

    PubMed

    Chen, Youdai; Zhou, Zongguang; Chen, Youqin; Wang, Zhao; Gao, Hongkai; Zheng, Xuelian

    2004-12-01

    The role of PACAP (pituitary adenylate cyclase activating polypeptide), a peptidergic transmitter, in the pathogenesis of acute pancreatitis is not yet clear. This experiment was conducted to examine the action of exogenous PACAP on rat pancreas and on the course of experimental acute pancreatitis. The results showed that 5-30 microg/kg of PACAP slightly raised the serum amylase level, induced pancreatic edema (23.88% +/- 2.532%-25.86% +/- 1.974% of experiment groups versus 29.21% +/- 5.657% of control group), inflammatory cell infiltration, vacuolization of acinar cells, and occasionally fatty and parenchymal necroses. 15-30 microg/kg of PACAP aggravated cerulein-induced acute pancreatitis; the pancreatic edema became more marked (13.45% +/- 2.045%-17.66% +/- 4.652% of expreiment groups versus 21.83% +/- 3.013% of cerulein group, P<0.05), the serum amylase level became higher; and ascites, pancreatic bleeding, fatty and parenchymal necroses, and extensive vacuolization of acinar cells appeared. For sodium taurocholate-induced pancreatitis, 5-10 microg/kg of PACAP mildly attenuated the pancreatic edema, reduced the serum amylase level (1986.91 +/- 710.97-2944.33 +/- 1182.47 IU/L vs 3690.87 +/- 2277.99 IU/L, P<0.05), whereas it caused multifocal hemorrhage and prominent necrosis in pancreas. Except the cerulein-induced pancreatitis groups, other groups were found to have reduced pancreatic functional capillary density (FCD); when pancreatic edema was taken into consideration and calibrated FCD was introduced (FCD weighted against pancreatic wet/dry ratio), all groups revealed increases in pancreatic functional capillaries when compared with normal control. In conclusion, PACAP is proinflammatory in the pathogenesis of acute pancreatitis, PACAP plus cerulein can induce acute hemorrhagic/necrotizing pancreatitis, and the action of PACAP on cerulein-induced panceatitis may differ from that on sodium taurocholate-induced one. In this experiment, pancreatic FCD was

  6. The alteration of profile analysis to accommodate testing functions

    NASA Technical Reports Server (NTRS)

    Myers, R. H.

    1979-01-01

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

  7. Pancreatic stellate cell: Pandora's box for pancreatic disease biology

    PubMed Central

    Bynigeri, Ratnakar R; Jakkampudi, Aparna; Jangala, Ramaiah; Subramanyam, Chivukula; Sasikala, Mitnala; Rao, G Venkat; Reddy, D Nageshwar; Talukdar, Rupjyoti

    2017-01-01

    Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin. PSCs maintain their activated phenotype via an autocrine loop involving different cytokines and contribute to progressive fibrosis in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC). Several pathways (e.g., JAK-STAT, Smad, Wnt signaling, Hedgehog etc.), transcription factors and miRNAs have been implicated in the inflammatory and profibrogenic function of PSCs. The role of PSCs goes much beyond fibrosis/desmoplasia in PDAC. It is now shown that PSCs are involved in significant crosstalk between the pancreatic cancer cells and the cancer stroma. These interactions result in tumour progression, metastasis, tumour hypoxia, immune evasion and drug resistance. This is the rationale for therapeutic preclinical and clinical trials that have targeted PSCs and the cancer stroma. PMID:28210075

  8. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection

    PubMed Central

    Gilliland, Taylor M.; Villafane-Ferriol, Nicole; Shah, Kevin P.; Shah, Rohan M.; Tran Cao, Hop S.; Massarweh, Nader N.; Silberfein, Eric J.; Choi, Eugene A.; Hsu, Cary; McElhany, Amy L.; Barakat, Omar; Fisher, William; Van Buren, George

    2017-01-01

    Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL). The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI) manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995–2016) addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC). We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1) patients with albumin < 2.5 mg/dL or weight loss > 10% should postpone surgery and begin aggressive nutrition supplementation; (2) patients with albumin < 3 mg/dL or weight loss between 5% and 10% should have nutrition supplementation prior to surgery; (3) enteral nutrition (EN) should be preferred as a nutritional intervention over total parenteral nutrition (TPN) postoperatively; and, (4) a multidisciplinary approach should be used to allow for early detection of symptoms of endocrine and exocrine pancreatic insufficiency alongside implementation of appropriate

  9. Functional regulation of sugar assimilation by N-glycan-specific interaction of pancreatic α-amylase with glycoproteins of duodenal brush border membrane.

    PubMed

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

    2012-06-29

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

  10. Transplantation of stem cells obtained from murine dental pulp improves pancreatic damage, renal function, and painful diabetic neuropathy in diabetic type 1 mouse model.

    PubMed

    Guimarães, Elisalva Teixeira; Cruz, Gabriela da Silva; Almeida, Tiago Farias de; Souza, Bruno Solano de Freitas; Kaneto, Carla Martins; Vasconcelos, Juliana Fraga; Santos, Washington Luis Conrado dos; Santos, Ricardo Ribeiro-dos; Villarreal, Cristiane Flora; Soares, Milena Botelho Pereira

    2013-01-01

    Diabetes mellitus (DM) is one of the most common and serious chronic diseases in the world. Here, we investigated the effects of mouse dental pulp stem cell (mDPSC) transplantation in a streptozotocin (STZ)-induced diabetes type 1 model. C57BL/6 mice were treated intraperitoneally with 80 mg/kg of STZ and transplanted with 1 × 10(6) mDPSCs or injected with saline, by an endovenous route, after diabetes onset. Blood and urine glucose levels were reduced in hyperglycemic mice treated with mDPSCs when compared to saline-treated controls. This correlated with an increase in pancreatic islets and insulin production 30 days after mDPSC therapy. Moreover, urea and proteinuria levels normalized after mDPSC transplantation in diabetic mice, indicating an improvement of renal function. This was confirmed by a histopathological analysis of kidney sections. We observed the loss of the epithelial brush border and proximal tubule dilatation only in saline-treated diabetic mice, which is indicative of acute renal lesion. STZ-induced thermal hyperalgesia was also reduced after cell therapy. Three days after transplantation, mDPSC-treated diabetic mice exhibited nociceptive thresholds similar to that of nondiabetic mice, an effect maintained throughout the 90-day evaluation period. Immunofluorescence analyses of the pancreas revealed the presence of GFP(+) cells in, or surrounding, pancreatic islets. Our results demonstrate that mDPSCs may contribute to pancreatic β-cell renewal, prevent renal damage in diabetic animals, and produce a powerful and long-lasting antinociceptive effect on behavioral neuropathic pain. Our results suggest stem cell therapy as an option for the control of diabetes complications such as intractable diabetic neuropathic pain.

  11. Pancreatic abscesses.

    PubMed

    Shi, E C; Yeo, B W; Ham, J M

    1984-09-01

    This paper presents the clinical features and problems in the management of 34 patients with pancreatic abscesses. In the majority of patients the abscesses developed following an attack of pancreatitis due to alcohol or gallstones. The abscesses were usually multilocular, and often had spread widely in the retroperitoneal space. Invasion into surrounding viscera or the peritoneal cavity occurred in 12 instances, and eight patients developed major bleeding into the abscess cavity. Obstructive complications (affecting bowel, common bile duct and large veins) occurred in eight patients. Twelve of the 34 patients (35 per cent) died, most deaths being due to failure to control sepsis (seven patients) or to massive bleeding from the abscess cavity (three patients). The mortality of this condition is likely to remain high, but may be reduced by better drainage techniques at the initial exploration. The importance of the infra-mesocolic approach for drainage is emphasized.

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

    PubMed

    Cheung, Heidi J; Cheung, Lawrence

    2015-01-01

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

  13. Protein-Binding Function of RNA-Dependent Protein Kinase Promotes Proliferation through TRAF2/RIP1/NF-κB/c-Myc Pathway in Pancreatic β cells

    PubMed Central

    Gao, LiLi; Tang, Wei; Ding, ZhengZheng; Wang, DingYu; Qi, XiaoQiang; Wu, HuiWen; Guo, Jun

    2015-01-01

    Double-stranded RNA-dependent protein kinase (PKR), an intracellular pathogen recognition receptor, is involved both in insulin resistance in peripheral tissues and in downregulation of pancreatic β-cell function in a kinase-dependent manner, indicating PKR as a core component in the progression of type 2 diabetes. PKR also acts as an adaptor protein via its protein-binding domain. Here, the PKR protein-binding function promoted β-cell proliferation without its kinase activity, which is associated with enhanced physical interaction with tumor necrosis factor receptor-associated factor 2 (TRAF2) and TRAF6. In addition, the transcription of the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB)-dependent survival gene c-Myc was upregulated significantly and is necessary for proliferation. Upregulation of the PKR protein-binding function induced the NF-κB pathway, as observed by dose-dependent degradation of IκBα, induced nuclear translocation of p65 and elevated NF-κB-dependent reporter gene expression. NF-κB-dependent reporter activity and β-cell proliferation both were suppressed by TRAF2-siRNA, but not by TRAF6-siRNA. TRAF2-siRNA blocked the ubiquitination of receptor-interacting serine/threonine-protein kinase 1 (RIP1) induced by PKR protein binding. Furthermore, RIP1-siRNA inhibited β-cell proliferation. Proinflammatory cytokines (TNFα) and glucolipitoxicity also promoted the physical interaction of PKR with TRAF2. Collectively, these data indicate a pivotal role for PKR’s protein-binding function on the proliferation of pancreatic β cells through TRAF2/RIP1/NF-κB/c-Myc pathways. Therapeutic opportunities for type 2 diabetes may arise when its kinase catalytic function, but not its protein-binding function, is downregulated. PMID:25715336

  14. [Pulmonary function testing before ablative methods].

    PubMed

    Ewert, R; Opitz, C

    2004-07-01

    Laser-induced thermotherapy (LITT) and radiofrequency thermoablation (RFTA) are increasingly used for pulmonary interventions. Primarily patients with severe functional limitations precluding a surgical approach are selected for these procedures. In this patient group a valid preinterventional risk assessment is of paramount importance. The occurrence of a pneumothorax is one of the most important complications associated with these procedures. Therefore, the functional capacity and pulmonary reserve of these patients should allow for at least short periods of lung collapse. The periinterventional risk of these patients can be estimated from basic lung function studies when certain comorbidities are excluded.

  15. 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.

  16. Transplantable pancreatic acinar carcinoma

    SciTech Connect

    Warren, J.R.; Reddy, J.K.

    1981-03-15

    Fragments of the nafenopin-induced pancreatic acinar cell carcinoma of rat have been examined in vitro for patterns of intracellular protein transport and carbamylcholine-induced protein discharge. Continuous incubation of the fragments with (3H)-leucine for 60 minutes resulted in labeling of rough endoplasmic reticulum, Golgi cisternae, and mature zymogen granules, revealed by electron microscope autoradiography. This result indicates transport of newly synthesized protein from the rough endoplasmic reticulum to mature zymogen granules in approximately 60 minutes. The secretagogue carbamylcholine induced the discharge of radioactive protein by carcinoma fragments pulse-chase labeled with (3H)-leucine. A maximal effective carbamylcholine concentration of 10(-5) M was determined. The acinar carcinoma resembles normal exocrine pancreas in the observed rate of intracellular protein transport and effective secretagogue concentration. However, the acinar carcinoma fragments demonstrated an apparent low rate of carbamylcholine-induced radioactive protein discharge as compared with normal pancreatic lobules or acinar cells. It is suggested that the apparent low rate of radioactive protein discharge reflects functional immaturity of the acinar carcinoma. Possible relationships of functional differentiation to the heterogeneous cytodifferentiation of the pancreatic acinar carcinoma are discussed.

  17. MiR-577 inhibits pancreatic β-cell function and survival by targeting fibroblast growth factor 21 (FGF-21) in pediatric diabetes.

    PubMed

    Chen, X Y; Li, G M; Dong, Q; Peng, H

    2015-12-01

    Pancreatic β-cell dysfunction is a central component of the pathogenesis of pediatric diabetes. MicroRNA (miRNA) have become one of the most encouraging and fruitful fields in biological research, and have been implicated as new players in the pathogenesis of diabetes and diabetes-associated complications. The role of miRNA in diabetes begins with the development of pancreatic islets. Fibroblast growth factor (FGF)-21 enhances glucose uptake in adipocytes, protecting transgenic animals from diet-induced obesity when overexpressed, and lowers blood glucose and triglyceride levels in diabetic animals (when administered); therefore, it is a good way to treat diabetes. However, the mechanism of miRNA in regulation of FGF21 is not known. In this study, FGF-21 was predicted to be the target of miR-577. Therefore, we investigated the effects of miR-577 on β-cell function and survival by targeting FGF-21. We demonstrated that, although FGF-21 does not acutely stimulate insulin secretion in isolated islets from normal rats, it increases insulin secretion and insulin content in diabetic islets and protects β-cells from apoptosis via the activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways.

  18. Reconstruction after pancreatic trauma by pancreaticogastrostomy

    PubMed Central

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

    2015-01-01

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

  19. [Tests of hand functionality in upper limb amputation with prosthesis].

    PubMed

    Bazzini, G; Orlandini, D; Moscato, T A; Nicita, D; Panigazzi, M

    2007-01-01

    The need for standardized instruments for clinical measurements has become pressing in the fields of occupational rehabilitation and ergonomics. This is particularly the case for instruments that allow a quantitative evaluation of upper limb function, and especially hand function in patients who have undergone an amputation and then application of an upper limb prosthesis. This study presents a review of the main tests used to evaluate hand function, with a critical analysis of their use in subjects with an upper limb prosthesis. The tests are divided into: tests to evaluate strength, tests to evaluate co-ordination and dexterity, tests of global or overall function, and tests proposed specifically for subjects with an upper limb prosthesis. Of the various tests presented, the authors give their preference to the Bimanual Functional Assessment, Abilhand and/or the ADL Questionnaire, because of the practical usefulness, clinimetric features, simplicity and ease of administration of these tests.

  20. Comparing acid steatocrit and faecal elastase estimations for use in M-ANNHEIM staging for pancreatitis

    PubMed Central

    Kamath, M Ganesh; Pai, C Ganesh; Kamath, Asha; Kurien, Annamma

    2017-01-01

    AIM To compare two tests for exocrine pancreatic function (EPF) for use in M-ANNHEIM staging for pancreatitis. METHODS One hundred and ninety four consecutive patients with acute pancreatitis (AP; n = 13), recurrent acute pancreatitis (RAP; n = 65) and chronic pancreatitis (CP; n = 116) were enrolled. EPF was assessed by faecal elastase-1 (FE-1) estimation and stool fat excretion by the acid steatocrit method. Patients were classified as per M-ANNHEIM stages separately based on the results of the two tests for comparison. Independent Student’s t-test, χ2 test, Kruskal-Wallis test, Mann-Whitney U test and McNemar’s test were used as appropriate. RESULTS Sixty-one (52.5%) patients with CP had steatorrhoea when assessed by the acid steatocrit method; 79 (68.1%) with CP had exocrine insufficiency by the FE-1 test (χ2 test, P < 0.001). The results of acid steatocrit and FE-1 showed a significant negative correlation (Spearman’s rho = -0.376, P < 0.001). A statistically significant difference was seen between the M-ANNHEIM stages as classified separately by acid steatocrit and the FE-1. Thirteen (6.7%), 87 (44.8%), 89 (45.8%) and 5 (2.5%) patients were placed in M-ANNHEIM stages 0, I, II, and III respectively, with the use of acid steatocrit as against 13 (6.7%), 85 (43.8%), 75 (38.6%), and 21 (10.8%) respectively by FE-1 in stages 0, I, II, and III thereby altering the stage in 28 (14.4%) patients (P < 0.001, McNemar’s test). CONCLUSION FE-1 estimation performed better than the acid steatocrit test for use in the staging of pancreatitis by the M-ANNHEIM classification since it diagnosed a higher proportion of patients with exocrine insufficiency.

  1. The Pancreatic Islet Regulome Browser

    PubMed Central

    Mularoni, Loris; Ramos-Rodríguez, Mireia; Pasquali, Lorenzo

    2017-01-01

    The pancreatic islet is a highly specialized tissue embedded in the exocrine pancreas whose primary function is that of controlling glucose homeostasis. Thus, understanding the transcriptional control of islet-cell may help to puzzle out the pathogenesis of glucose metabolism disorders. Integrative computational analyses of transcriptomic and epigenomic data allows predicting genomic coordinates of putative regulatory elements across the genome and, decipher tissue-specific functions of the non-coding genome. We herein present the Islet Regulome Browser, a tool that allows fast access and exploration of pancreatic islet epigenomic and transcriptomic data produced by different labs worldwide. The Islet Regulome Browser is now accessible on the internet or may be installed locally. It allows uploading custom tracks as well as providing interactive access to a wealth of information including Genome-Wide Association Studies (GWAS) variants, different classes of regulatory elements, together with enhancer clusters, stretch-enhancers and transcription factor binding sites in pancreatic progenitors and adult human pancreatic islets. Integration and visualization of such data may allow a deeper understanding of the regulatory networks driving tissue-specific transcription and guide the identification of regulatory variants. We believe that such tool will facilitate the access to pancreatic islet public genomic datasets providing a major boost to functional genomics studies in glucose metabolism related traits including diabetes. PMID:28261261

  2. 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…

  3. Functional ground testing - Evaluating the Tomahawk Cruise Missile

    SciTech Connect

    Parise, K.W. )

    1992-01-01

    Flight testing evaluates vehicle performance in a flight environment and, in the case of a weapon system, clearly indicates mission readiness. However, there is a cost-effective alternative method of testing which is capable of indicating weapon system functionality and subsystem success. Functional ground testing of the all-up round Tomahawk Cruise Missile is described. The Tomahawk functional ground test (FGT) cannot make the same conclusive determinations that an operational test launch can. This paper describes the Tomahawk FGT and what makes it unique. It describes the developments and status of this testing methodology, the data acquisition and control, and the engineering challenges encountered. 3 refs.

  4. Assessing Differential Item Functioning in Performance Tests.

    ERIC Educational Resources Information Center

    Zwick, Rebecca; And Others

    Although the belief has been expressed that performance assessments are intrinsically more fair than multiple-choice measures, some forms of performance assessment may in fact be more likely than conventional tests to tap construct-irrelevant factors. As performance assessment grows in popularity, it will be increasingly important to monitor the…

  5. Practical Aspects of Functional Testing Techniques.

    DTIC Science & Technology

    2014-09-26

    automated information system in the NIAM method. In an existing system an inventory of all the functions (represented by verbs) which the information...with automated systems it is 2) which poses the major problem. 3.5. Ellipsis. Substitution and Informality These processes produce sentence fragments...and Conclusion 97 Appendix System Development Life Cycle 100 Glossary 132 References 135 A7 / 1 t Abstract This document reports an investigation into

  6. Arterio-Pancreatic Syndrome

    PubMed Central

    Lee, Ser Yee; Ng, Kheng Hong; Sebastian, Mathew George

    2011-01-01

    Acute pancreatitis is a single-organ disorder that has multi-organ sequelae. As a result, it can have varied presentations. Acute pancreatitis presenting as acute limb ischemia is rare. We present a patient with acute pancreatitis presenting with bilateral lower limb ischemia. The episode of acute pancreatitis resolved but the acute lower limb ischemia precipitated as the pancreatitis progressed, and necessitated bilateral above-knee amputations. We review the literature and discuss the pathogenesis of such a phenomenon. PMID:22347150

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

    PubMed

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

    2015-08-03

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

  8. 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.

  9. Endoscopic naso-pancreatic drainage for the treatment of pancreatic fistula occurring after LDLT.

    PubMed

    Nagatsu, Akihisa; Taniguchi, Masahiko; Shimamura, Tsuyoshi; Suzuki, Tomomi; Yamashita, Kenichiro; Kawakami, Hiroshi; Abo, Daisuke; Kamiyama, Toshiya; Furukawa, Hiroyuki; Todo, Satoru

    2011-08-14

    Pancreatic fistula is a quite rare complication in patients who undergo living donor liver transplantation (LDLT). However, in the cases that show pancreatic fistula, the limited volume of the graft and the resultant inadequate liver function may complicate the management of the fistula. As a result, the pancreatic fistula may result in the death of the patient. We present 2 cases in which endoscopic treatment was effective against pancreatic fistulas that developed after LDLT. In case 1, a 61-year-old woman underwent LDLT for primary biliary cirrhosis. Because of a portal venous thrombus caused by a splenorenal shunt, the patient underwent portal vein reconstruction, and a splenorenal shunt was ligated on postoperative day (POD) 7. The main pancreatic duct was injured during the manipulation to achieve hemostasis, thereby necessitating open drainage. However, discharge of pancreatic fluid continued even after POD 300. Endoscopic naso-pancreatic drainage (ENPD) was performed, and this procedure resulted in a remarkable decrease in drain output. The refractory pancreatic fistula healed on day 40 after ENPD. In case 2, a 58-year-old man underwent LDLT for cirrhosis caused by the hepatitis C virus. When the portal vein was exposed during thrombectomy, the pancreatic head was injured, which led to the formation of a pancreatic fistula. Conservative therapy was ineffective; therefore, ENPD was performed. The pancreatic fistula healed on day 38 after ENPD. The findings in these 2 cases show that endoscopic drainage of the main pancreatic duct is a less invasive and effective treatment for pancreatic fistulas that develop after LDLT.

  10. Axial force measurement for esophageal function testing

    PubMed Central

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

    2009-01-01

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

  11. Thyroid function tests during carbimazole therapy.

    PubMed Central

    Scott, D. L.; Tymms, D. J.; Taylor, M. A.; Chapman, C.

    1980-01-01

    Changes in plasma thyroxine (T4), triiodothyronine (T3), free thyroxine index (FT4I) and thyroid stimulating hormone were studied in 100 patients with Graves' disease treated with carbimazole. During therapy plasma T3 concentrations were disproportionately high compared to those of T4, the T4 : T3 ratio was low, and many patients were clinically euthyroid with a normal plasma T3 but low T4 concentration. Although there was considerable individual variation in response, the order of response was always the same with plasma T4 falling to normal or low levels before T3. Plasma T3 was the best indicator of clinical status and the best predictor of the impending change; additional information of changes in thyroid status was obtained from plasma T4 and FT4I estimation, especially when these were followed sequentially. Single measurements of T4 or FT4I only are not recommended for assessing thyroid function during carbimazole therapy. PMID:6894979

  12. [Syncope: electrocardiogram and autonomic function tests].

    PubMed

    Uribe, William; Baranchuk, Adrián; Botero, Federico

    2016-12-23

    Syncope represents one of the most frequent reasons for consultation in the emergency department. A proper identification will allow a precise etiologic approach and the optimization of delivery of health resources.
Once knowing the classification of syncope; it is the clinical interrogatory what enables to discriminate which of these patients present with a neurogenic mediated syncope or a cardiac mediated syncope. The use of diagnostic methods such as the tilt test, will clarify what type of neurally mediated syncope predominates in the patient.
The electrocardiogram is the cornerstone in the identification of those patients who had a true episode of self-limited or aborted sudden death as the first manifestation of their syncope, a fact which provides prognostic and therapeutic information that will impact the morbidity and mortality.

  13. 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

  14. Optimized sample preparation of endoscopic collected pancreatic fluid for SDS-PAGE analysis.

    PubMed

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

    2010-07-01

    The standardization of methods for human body fluid protein isolation is a critical initial step for proteomic analyses aimed to discover clinically relevant biomarkers. Several caveats have hindered pancreatic fluid proteomics, including the heterogeneity of samples and protein degradation. We aim to optimize sample handling of pancreatic fluid that has been collected using a safe and effective endoscopic collection method (endoscopic pancreatic function test). Using SDS-PAGE protein profiling, we investigate (i) precipitation techniques to maximize protein extraction, (ii) auto-digestion of pancreatic fluid following prolonged exposure to a range of temperatures, (iii) effects of multiple freeze-thaw cycles on protein stability, and (iv) the utility of protease inhibitors. Our experiments revealed that TCA precipitation resulted in the most efficient extraction of protein from pancreatic fluid of the eight methods we investigated. In addition, our data reveal that although auto-digestion of proteins is prevalent at 23 and 37 degrees C, incubation on ice significantly slows such degradation. Similarly, when the sample is maintained on ice, proteolysis is minimal during multiple freeze-thaw cycles. We have also determined the addition of protease inhibitors to be assay-dependent. Our optimized sample preparation strategy can be applied to future proteomic analyses of pancreatic fluid.

  15. 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

  16. Isoform-specific regulation of mood behavior and pancreatic β cell and cardiovascular function by L-type Ca2+ channels

    PubMed Central

    Sinnegger-Brauns, Martina J.; Hetzenauer, Alfred; Huber, Irene G.; Renström, Erik; Wietzorrek, Georg; Berjukov, Stanislav; Cavalli, Maurizio; Walter, Doris; Koschak, Alexandra; Waldschütz, Ralph; Hering, Steffen; Bova, Sergio; Rorsman, Patrik; Pongs, Olaf; Singewald, Nicolas; Striessnig, Jörg

    2004-01-01

    Cav1.2 and Cav1.3 L-type Ca2+ channels (LTCCs) are believed to underlie Ca2+ currents in brain, pancreatic β cells, and the cardiovascular system. In the CNS, neuronal LTCCs control excitation-transcription coupling and neuronal plasticity. However, the pharmacotherapeutic implications of CNS LTCC modulation are difficult to study because LTCC modulators cause card iovascular (activators and blockers) and neurotoxic (activators) effects. We selectively eliminated high dihydropyridine (DHP) sensitivity from Cav1.2 α1 subunits (Cav1.2DHP–/–) without affecting function and expression. This allowed separation of the DHP effects of Cav1.2 from those of Cav1.3 and other LTCCs. DHP effects on pancreatic β cell LTCC currents, insulin secretion, cardiac inotropy, and arterial smooth muscle contractility were lost in Cav1.2DHP–/– mice, which rules out a direct role of Cav1.3 for these physiological processes. Using Cav1.2DHP–/– mice, we established DHPs as mood-modifying agents: LTCC activator–induced neurotoxicity was abolished and disclosed a depression-like behavioral effect without affecting spontaneous locomotor activity. LTCC activator BayK 8644 (BayK) activated only a specific set of brain areas. In the ventral striatum, BayK-induced release of glutamate and 5-HT, but not dopamine and noradrenaline, was abolished. This animal model provides a useful tool to elucidate whether Cav1.3-selective channel modulation represents a novel pharmacological approach to modify CNS function without major peripheral effects. PMID:15146240

  17. 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

  18. [External pancreatic fistulas management].

    PubMed

    Stepan, E V; Ermolov, A S; Rogal', M L; Teterin, Yu S

    2017-01-01

    The main principles of treatment of external postoperative pancreatic fistulas are viewed in the article. Pancreatic trauma was the reason of pancreatic fistula in 38.7% of the cases, operations because of acute pancreatitis - in 25.8%, and pancreatic pseudocyst drainage - in 35.5%. 93 patients recovered after the treatment. Complex conservative treatment of EPF allowed to close fistulas in 74.2% of the patients with normal patency of the main pancreatic duct (MPD). The usage of octreotide 600-900 mcg daily for at least 5 days to decrease pancreatic secretion was an important part of the conservative treatment. Endoscopic papillotomy was performed in patients with major duodenal papilla obstruction and interruption of transporting of pancreatic secretion to duodenum. Stent of the main pancreatic duct was indicated in patients with extended pancreatic duct stenosis to normalize transport of pancreatic secretion to duodenum. Surgical formation of anastomosis between distal part of the main pancreatic duct and gastro-intestinal tract was carried out when it was impossible to fulfill endoscopic stenting of pancreatic duct either because of its interruption and diastasis between its ends, or in the cases of unsuccessful conservative treatment of external pancreatic fistula caused by drainage of pseudocyst.

  19. Significance tests for functional data with complex dependence structure

    PubMed Central

    Lahiri, Soumen N.; Carroll, Raymond J.

    2015-01-01

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

  20. Primary Cilia in Pancreatic Development and Disease

    PubMed Central

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

    2014-01-01

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

  1. 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…

  2. Necrotizing pancreatitis: diagnosis, imaging, and intervention.

    PubMed

    Shyu, Jeffrey Y; Sainani, Nisha I; Sahni, V Anik; Chick, Jeffrey F; Chauhan, Nikunj R; Conwell, Darwin L; Clancy, Thomas E; Banks, Peter A; Silverman, Stuart G

    2014-01-01

    Acute necrotizing pancreatitis is a severe form of acute pancreatitis characterized by necrosis in and around the pancreas and is associated with high rates of morbidity and mortality. Although acute interstitial edematous pancreatitis is diagnosed primarily on the basis of signs, symptoms, and laboratory test findings, the diagnosis and severity assessment of acute necrotizing pancreatitis are based in large part on imaging findings. On the basis of the revised Atlanta classification system of 2012, necrotizing pancreatitis is subdivided anatomically into parenchymal, peripancreatic, and combined subtypes, and temporally into clinical early (within 1 week of onset) and late (>1 week after onset) phases. Associated collections are categorized as "acute necrotic" or "walled off" and can be sterile or infected. Imaging, primarily computed tomography and magnetic resonance imaging, plays an essential role in the diagnosis of necrotizing pancreatitis and the identification of complications, including infection, bowel and biliary obstruction, hemorrhage, pseudoaneurysm formation, and venous thrombosis. Imaging is also used to help triage patients and guide both temporizing and definitive management. A "step-up" method for the management of necrotizing pancreatitis that makes use of imaging-guided percutaneous catheter drainage of fluid collections prior to endoscopic or surgical necrosectomy has been shown to improve clinical outcomes. The authors present an algorithmic approach to the care of patients with necrotizing pancreatitis and review the use of imaging and interventional techniques in the diagnosis and management of this pathologic condition.

  3. 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.

  4. 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…

  5. Modulation of Glucose Metabolism by Balanced Deep-Sea Water Ameliorates Hyperglycemia and Pancreatic Function in Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Ha, Byung Geun; Park, Jung-Eun; Shin, Eun Ji; Shon, Yun Hee

    2014-01-01

    The aim of this study was to determine the effects of balanced deep-sea water (BDSW) on hyperglycemia and glucose intolerance in streptozotocin (STZ)-induced diabetic mice. BDSW was prepared by mixing DSW mineral extracts and desalinated water to yield a final hardness of 1000–4000 ppm. Male ICR mice were assigned to 6 groups; mice in each group were given tap water (normal and STZ diabetic groups) or STZ with BDSW of varying hardness (0, 1000, 2000, and 4000 ppm) for 4 weeks. The STZ with BDSW group exhibited lowered fasting plasma glucose levels than the STZ-induced diabetic group. Oral glucose tolerance tests showed that BDSW improves impaired glucose tolerance in STZ-induced diabetic mice. Histopathological evaluation of the pancreas showed that BDSW restores the morphology of the pancreatic islets of Langerhans and increases the secretion of insulin in STZ-induced diabetic mice. Quantitative real-time PCR assay revealed that the expression of hepatic genes involved in gluconeogenesis, glucose oxidation, and glycogenolysis was suppressed, while the expression of the genes involved in glucose uptake, β-oxidation, and glucose oxidation in muscle were increased in the STZ with BDSW group. BDSW stimulated PI3-K, AMPK, and mTOR pathway-mediated glucose uptake in C2C12 myotubes. BDSW increased AMPK phosphorylation in C2C12 myotubes and improved impaired AMPK phosphorylation in the muscles of STZ-induced diabetic mice. Taken together, these results suggest that BDSW is a potential anti-diabetic agent, owing to its ability to suppress hyperglycemia and improve glucose intolerance by modulating glucose metabolism, recovering pancreatic islets of Langerhans and increasing glucose uptake. PMID:25013896

  6. 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

  7. Pancreatic Cancer Stage 3

    MedlinePlus

    ... 3 Description: Stage III pancreatic cancer; drawing shows cancer in the pancreas, common hepatic artery, and portal vein. Also shown ... and superior mesenteric artery. Stage III pancreatic cancer. Cancer ... near the pancreas. These include the superior mesenteric artery, celiac axis, ...

  8. Surgery for pancreatic cancer

    MedlinePlus

    ... medlineplus.gov/ency/article/007649.htm Surgery for pancreatic cancer To use the sharing features on this page, ... surgery are used in the surgical treatment of pancreatic cancer. Whipple procedure: This is the most common surgery ...

  9. Pancreatic pseudocysts and aneurysms

    PubMed Central

    Andrén-Sandberg, Åke

    2010-01-01

    A number of methods are available for the drainage of pancreatic pseudocysts, including percutaneous, endoscopic and open approaches. The author reviewed the most rently reports, and and summarized the latest advances in the pancreatic pseudocysts. PMID:22558566

  10. Pathogenic mechanisms of pancreatitis.

    PubMed

    Manohar, Murli; Verma, Alok Kumar; Venkateshaiah, Sathisha Upparahalli; Sanders, Nathan L; Mishra, Anil

    2017-02-06

    Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in promoting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways (i.e., Transforming growth factor-β/SMAD, mitogen-activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8 IL-10, IL-18, IL-33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for

  11. Pathogenic mechanisms of pancreatitis

    PubMed Central

    Manohar, Murli; Verma, Alok Kumar; Venkateshaiah, Sathisha Upparahalli; Sanders, Nathan L; Mishra, Anil

    2017-01-01

    Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in promoting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways (i.e., Transforming growth factor-β/SMAD, mitogen-activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8 IL-10, IL-18, IL-33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for

  12. Modeling formalin fixation and antigen retrieval with bovine pancreatic ribonuclease A: I—Structural and functional alterations

    PubMed Central

    Rait, Vladimir K; O’Leary, Timothy J; Mason, Jeffrey T

    2006-01-01

    Understanding the chemistry of protein modification by formaldehyde is central to developing improved methods to recover proteins from formalin-fixed paraffin-embedded tissues for proteomic analysis and to improve protein immunoreactivity for immunohistochemical studies. We used biophysical techniques to investigate the effects of formaldehyde treatment on bovine pancreatic ribonuclease A (RNase A). Treatment of RNase A with formaldehyde was shown by gel electrophoresis to lead to the rapid formation of intra- and intermolecular protein cross-links. Thermal studies revealed that these protein cross-links significantly increased the thermal denaturation temperature of RNase A preparations. Analysis of formaldehyde-treated RNase A oligomers isolated by gel chromatography revealed that intramolecular protein cross-links are primarily responsible for the increase in protein thermostability. Formaldehyde treatment also lowered the isoelectric point of the enzyme from 9.45 to the 6.0–7.4 range. Optical spectroscopic studies demonstrated that the formaldehyde-induced modifications did not significantly alter the secondary or tertiary structure of RNase A. Heating formaldehyde-treated RNase A at 65°C resulted in a significant reversal of the protein intra- and intermolecular cross-links and led to a partial restoration of enzymatic activity. PMID:14968117

  13. Low plasma adiponectin level, white blood cell count and Helicobacter pylori titre independently predict abnormal pancreatic beta-cell function.

    PubMed

    So, Wing-Yee; Tong, Peter C; Ko, Gary T; Ma, Ronald C; Ozaki, Risa; Kong, Alice P; Yang, Xilin; Ho, Chung-Shun; Lam, Christopher C; Chan, Juliana C

    2009-11-01

    Adiponectin is an adipocytokine with insulin sensitizing effect while chronic inflammation damages pancreatic beta-cells leading to reduced insulin response. We aimed to prove the hypothesis that adiponectin levels and inflammatory markers (white blood cell counts [WCC], Helicobacter pylori [HP] titers, high sensitivity C-reactive protein [hs-CRP]) may interact to affect risk of diabetes. We studied 288 Chinese men (age-median: 41.0 years, IQR: 35.3-46.0 years) being recruited from the community in Hong Kong. The mean adiponectin level was 5.39+/-2.81 microg/ml and 40.9% (n=107) had low adiponectin level (<4 microg/ml). On multiple regression analysis, adiponectin was negatively associated with diabetes, HOMA insulin resistance top quartile, plasma glucose (PG) and 2h insulin; and positively associated with HOMA insulin sensitivity index. WCC was independently associated with PG and 15' insulin, and negatively associated with HOMA insulin sensitivity top quartile. HP titre was associated with 30' PG level and diabetes. hs-CRP did not enter the multivariable model. In conclusion, adiponectin, WCC and HP titer are independent predictors for hyperglycemia and reduced insulin sensitivity in Chinese men. These findings may explain the high risk for diabetes in Chinese population despite their relatively low adiposity.

  14. Experimental Models of Pancreatitis

    PubMed Central

    Hyun, Jong Jin

    2014-01-01

    Acute pancreatitis is an inflammatory disease characterized by interstitial edema, inflammatory cell infiltration, and acinar cell necrosis, depending on its severity. Regardless of the extent of tissue injury, acute pancreatitis is a completely reversible process with evident normal tissue architecture after recovery. Its pathogenic mechanism has been known to be closely related to intracellular digestive enzyme activation. In contrast to acute pancreatitis, chronic pancreatitis is characterized by irreversible tissue damage such as acinar cell atrophy and pancreatic fibrosis that results in exocrine and endocrine insufficiency. Recently, many studies of chronic pancreatitis have been prompted by the discovery of the pancreatic stellate cell, which has been identified and distinguished as the key effector cell of pancreatic fibrosis. However, investigations into the pathogenesis and treatment of pancreatitis face many obstacles because of its anatomical location and disparate clinical course. Due to these difficulties, most of our knowledge on pancreatitis is based on research conducted using experimental models of pancreatitis. In this review, several experimental models of pancreatitis will be discussed in terms of technique, advantages, and limitations. PMID:24944983

  15. 33 CFR 157.12f - Workshop functional test requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... SECURITY (CONTINUED) POLLUTION RULES FOR THE PROTECTION OF THE MARINE ENVIRONMENT RELATING TO TANK VESSELS CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12f Workshop functional test requirements... exceed the capacity of the system....

  16. 33 CFR 157.12f - Workshop functional test requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SECURITY (CONTINUED) POLLUTION RULES FOR THE PROTECTION OF THE MARINE ENVIRONMENT RELATING TO TANK VESSELS CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12f Workshop functional test requirements... exceed the capacity of the system....

  17. 33 CFR 157.12f - Workshop functional test requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... SECURITY (CONTINUED) POLLUTION RULES FOR THE PROTECTION OF THE MARINE ENVIRONMENT RELATING TO TANK VESSELS CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12f Workshop functional test requirements... exceed the capacity of the system....

  18. 33 CFR 157.12f - Workshop functional test requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SECURITY (CONTINUED) POLLUTION RULES FOR THE PROTECTION OF THE MARINE ENVIRONMENT RELATING TO TANK VESSELS CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12f Workshop functional test requirements... exceed the capacity of the system....

  19. A Semi-Automated Functional Test Data Analysis Tool

    SciTech Connect

    Xu, Peng; Haves, Philip; Kim, Moosung

    2005-05-01

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

  20. 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.

  1. [Portable lung function parameters testing system based on DSP].

    PubMed

    Guo, Zhanshe; Yuan, Minzhong; Zhou, Hui

    2012-11-01

    Lung function monitoring is a critical technique for clinical medicine. Currently, the lung function testing devices used in our domestic hospitals are both expensive and bulky. A portable and accurate lung function parameters testing system is highly desired and is proposed in this paper. The hardware of the system is based on DSP technology. The breathing passage is designed with an aim suitable for the breathe and signal detection. We use the direct detection method to detect the gas flow, the breathing passage pressure and the breathing time. Thanks to the powerful data processing ability and the high operation speed of the DSP, breathing signals can be easily analyzed. Thus, several lung function parameters of clinical significance can be obtained. Experiments show that the accuracy of the system is better than 3%, and could meet the demand of the lung function testing.

  2. 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.

  3. Chronic pancreatitis: relation to acute pancreatitis and pancreatic cancer.

    PubMed

    Uomo, G; Rabitti, P G

    2000-01-01

    The relationship between chronic pancreatitis (CP) and other pancreatic diseases, such as acute pancreatitis (AP) and pancreatic cancer (PK), remains a fairly debated question. The progression from alcoholic AP to CP is controversial, and some long-term epidemiological studies suggest that alcoholic CP might be the result of recurrent alcoholic AP (necrosis-fibrosis sequence) and a subgroup of alcoholics may present recurrent AP without progression to CP. Other predisposing factors (genetic, nutritional, environmental) seems to be important in inducing different outcomes of pancreatic damage due to alcohol. However, recurrent episodes of AP are clearly involved in pathophysiology of CP in patients with hereditary pancreatitis. A relationship between CP and subsequent PK development has long been suspected, but we actually don't know whether this association is direct or is the result of confounding factors, such as alcohol intake or cigarette smoking. Many issues should be considered as indicators of a causal association, and several of them are not fulfilled. Nonetheless, epidemiological studies (case-control or cohort studies) showed that the risk of PK is increased in patients with CP; the risk is significantly higher in tropical calcifying CP and hereditary pancreatitis. Studies on growth factors, oncogenes, tumor-suppressor genes, and angiogenesis suggest that the sequence PC-KP is plausible from the biological standpoint.

  4. 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.

  5. 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...

  6. A Use of the Information Function in Tailored Testing

    ERIC Educational Resources Information Center

    Samejima, Fumiko

    1977-01-01

    Several important implications in latent trait theory, with implications for individualized or tailored testing, are pointed out. A way of using the information function in tailored testing in connection with the standard error estimation of the ability level using maximum likelihood estimation is suggested. (Author/JKS)

  7. 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.

  8. Duodenal-jejunal bypass normalizes pancreatic islet proliferation rate and function but not hepatic steatosis in hypothalamic obese rats.

    PubMed

    Cantelli, K R; Soares, G M; Ribeiro, R A; Balbo, S L; Lubaczeuski, C; Boschero, A C; Araújo, A C F; Bonfleur, M L

    2017-03-30

    Modifications in life-style and/or pharmacotherapies contribute to weight loss and ameliorate the metabolic profile of diet-induced obese humans and rodents. Since these strategies fail to treat hypothalamic obesity, we have assessed the possible mechanisms by which duodenal-jejunal bypass (DJB) surgery regulates hepatic lipid metabolism and the morphophysiology of pancreatic islets, in hypothalamic obese (HyO) rats. During the first 5 days of life, male Wistar rats received subcutaneous injections of monosodium glutamate (4 g/kg body weight, HyO group), or saline (CTL). At 90 days of age, HyO rats were randomly subjected to DJB (HyO DJB group) or sham surgery (HyO Sham group). HyO Sham rats were morbidly obese, insulin resistant, hypertriglyceridemic and displayed higher serum concentrations of non-esterified fatty acids (NEFA) and hepatic triglyceride (TG). These effects were associated with higher expressions of the lipogenic genes and fatty acid synthase (FASN) protein content in the liver. Furthermore, hepatic genes involved in β-oxidation and TG export were down-regulated in HyO rats. In addition, these rats exhibited hyperinsulinemia, β-cell hypersecretion, a higher percentage of islets and β-cell area/pancreas section, and enhanced nuclear content of Ki67 protein in islet-cells. At 2 months after DJB surgery, serum concentrations of TG and NEFA, but not hepatic TG accumulation and gene and protein expressions, were normalized in HyO rats. Insulin release and Ki67 positive cells were also normalized in HyO DJB islets. In conclusion, DJB decreased islet-cell proliferation, normalized insulinemia, and ameliorated insulin sensitivity and plasma lipid profile, independently of changes in hepatic metabolism.

  9. 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.

  10. Chronic pancreatitis: Multicentre prospective data collection and analysis by the Hungarian Pancreatic Study Group

    PubMed Central

    Szücs, Ákos; Marjai, Tamás; Szentesi, Andrea; Farkas, Nelli; Párniczky, Andrea; Nagy, György; Kui, Balázs; Takács, Tamás; Czakó, László; Szepes, Zoltán; Németh, Balázs Csaba; Vincze, Áron; Pár, Gabriella; Szabó, Imre; Sarlós, Patrícia; Illés, Anita; Gódi, Szilárd; Izbéki, Ferenc; Gervain, Judit; Halász, Adrienn; Farkas, Gyula; Leindler, László; Kelemen, Dezső; Papp, Róbert; Szmola, Richárd; Varga, Márta; Hamvas, József; Novák, János; Bod, Barnabás; Sahin-Tóth, Miklós; Hegyi, Péter

    2017-01-01

    Introduction Chronic pancreatitis is an inflammatory disease associated with structural and functional damage to the pancreas, causing pain, maldigestion and weight loss and thus worsening the quality of life. Aims and methods Our aim was to find correlations from a multicentre database representing the epidemiological traits, diagnosis and treatment of the disease in Hungary. The Hungarian Pancreatic Study Group collected data prospectively from 2012 to 2014 on patients suffering from chronic pancreatitis. Statistical analysis was performed on different questions. Results Data on 229 patients (74% male and 26% female) were uploaded from 14 centres. Daily alcohol consumption was present in the aetiology of 56% of the patients. 66% of the patients were previously treated for acute exacerbation. One third of the patients had had previous endoscopic or surgical interventions. Pain was present in 69% of the cases, endocrine insufficiency in 33%, diarrhoea in 13% and weight loss in 39%. Diagnosis was confirmed with US (80%), CT scan (52%), MRI-MRCP (6%), ERCP (39%), and EUS (7,4%). A functional test was carried out in 5% of the patients. In 31% of the cases, an endoscopic intervention was performed with the need for re-intervention in 5%. Further elective surgical intervention was necessitated in 44% of endoscopies. 20% of the registered patients were primarily treated with surgery. The biliary complication rate for surgery was significantly smaller (2%) than endoscopy (27%); however, pancreatic complications were higher in the patients treated with surgery. Patients who smoked regularly needed significantly more surgical intervention following endoscopy (66.7% vs. 26.9%, p = 0.002) than non-smokers, and the ratio of surgical intervention alone was also significantly higher (27.3% vs. 10.8%, p = 0.004). The ratio of surgery in patients who smoked and drank was significantly higher (30.09% vs. 12.5%, p = 0.012) than in abstinent and non-smoking patients, similarly to the

  11. 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

  12. Inherited pancreatic cancer syndromes.

    PubMed

    Solomon, Sheila; Das, Siddhartha; Brand, Randall; Whitcomb, David C

    2012-01-01

    Pancreatic cancer remains one of the most challenging of all cancers. Genetic risk factors are believed to play a major role, but other than genes coding for blood group, genetic risks for sporadic cases remain elusive. However, several germline mutations have been identified that lead to hereditary pancreatic cancer, familial pancreatic cancer, and increased risk for pancreatic cancer as part of a familial cancer syndrome. The most important genes with variants increasing risk for pancreatic cancer include BRCA1, BRCA2, PALB2, ATM, CDKN2A, APC, MLH1, MSH2, MSH6, PMS2, PRSS1, and STK11. Recognition of members of high-risk families is important for understanding pancreatic cancer biology, for recommending risk reduction strategies and, in some cases, initiating cancer surveillance programs. Because the best methods for surveillance have not been established, the recommendation to refer at-risk patients to centers with ongoing research programs in pancreatic cancer surveillance is supported.

  13. [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.

  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. PMID:27622194

  15. 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

  16. Metastin and its variant forms suppress migration of pancreatic cancer cells.

    PubMed

    Masui, Toshihiko; Doi, Ryuichiro; Mori, Tomohiko; Toyoda, Eiji; Koizumi, Masayuki; Kami, Kazuhiro; Ito, Daisuke; Peiper, Stephen C; Broach, James R; Oishi, Shinya; Niida, Ayumu; Fujii, Nobutaka; Imamura, Masayuki

    2004-02-27

    Metastin, a post-translationally modified variant of KiSS1, was recently identified as an endogenous peptide agonist for a novel G-protein coupled receptor, hOT7T175 (AXOR12, GPR54). In this study, we analyzed the role of KiSS1 and hOT7T175 in both pancreatic cancer tissues and pancreatic cancer cell lines. Furthermore, we synthesized novel short variant forms of metastin and tested the inhibitory effect of those variants on in vitro cell functions that are relevant to metastasis. Pancreatic cancer tissues showed significantly lower expression of KiSS1 mRNA than normal tissues (p=0.018), while cancer tissues showed significantly higher expression of hOT7T175 mRNA than normal pancreatic tissues (p=0.027). In human pancreatic cancer cell lines, KiSS1 mRNA was highly expressed in 2 out of 6 pancreatic cancer cell lines, while hOT7T175 mRNA was expressed in all cell lines at various degrees. PANC-1 cells showed the highest expression of hOT7T175. Exogenous metastin did not suppress cell proliferation but significantly reduced the in vitro migration of PANC-1 cells (p<0.01). Metastin induced activation of ERK1 in PANC-1 and AsPC-1 cells. Finally, we synthesized 3 novel short variant forms of metastin, FM053a2TFA, FM059a2TFA, and FM052a4TFA. These metastin variants significantly suppressed the migration of PANC-1 cells and activated ERK1. These data suggest that the metastin receptor, hOT7T175, is one of the promising targets for suppression of metastasis, and that small metastin variants could be an anti-metastatic agent to pancreatic cancer.

  17. 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.

  18. 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.

  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. 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

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

    PubMed

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

    2012-03-01

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

  2. Emerging roles for β-arrestin-1 in the control of the pancreatic β-cell function and mass: new therapeutic strategies and consequences for drug screening.

    PubMed

    Dalle, Stéphane; Ravier, Magalie A; Bertrand, Gyslaine

    2011-03-01

    Defective insulin secretion is a feature of type 2 diabetes that results from inadequate compensatory increase in β-cell mass, decreased β-cell survival and impaired glucose-dependent insulin release. Pancreatic β-cell proliferation, survival and secretion are thought to be regulated by signalling pathways linked to G-protein coupled receptors (GPCRs), such as the glucagon-like peptide-1 (GLP-1) and the pituitary adenylate cyclase-activating polypeptide (PACAP) receptors. β-arrestin-1 serves as a multifunctional adaptor protein that mediates receptor desensitization, receptor internalization, and links GPCRs to downstream pathways such as tyrosine kinase Src, ERK1/2 or Akt/PKB. Importantly, recent studies found that β-arrestin-1 mediates GLP-1 signalling to insulin secretion, GLP-1 antiapoptotic effect by phosphorylating the proapoptotic protein Bad through ERK1/2 activation, and PACAP potentiation of glucose-induced long-lasting ERK1/2 activation controlling IRS-2 expression. Together, these novel findings reveal an important functional role for β-arrestin-1 in the regulation of insulin secretion and β-cell survival by GPCRs.

  3. The PARK2 gene is involved in the maintenance of pancreatic β-cell functions related to insulin production and secretion.

    PubMed

    Jin, Hyun-Seok; Kim, Jeonghyun; Lee, Soo-Jin; Kim, Kyunga; Go, Min Jin; Lee, Jong-Young; Lee, Hye-Ja; Song, Jihyun; Jeon, Byeong Tak; Roh, Gu Seob; Kim, Sung-Jun; Kim, Bo-Young; Hong, Kyung-Won; Yoo, Young-Hyun; Oh, Beomseok; Kang, Yup; Jeong, Seon-Yong

    2014-01-25

    Several association studies have implicated the PARK2 gene that encodes parkin--the key molecule orchestrating the mitochondrial quality control system--as a candidate susceptibility gene for diabetes. A total of 7551 unrelated Korean KARE cohort subjects were analyzed to investigate the association between the PARK2 single nucleotide polymorphism (SNP) and quantitative glycemic traits. Two SNPs, rs10455889 and rs9365294, were significantly associated with fasting plasma glucose level (p=∼1.2×10(-4)) and insulin secretion indices (p=∼7.4×10(-5)) in male KARE subjects. Parkin was expressed predominantly in the rat pancreatic islets. Downregulation of the Park2 gene in rat INS-1 β-cells resulted in a significant decrease in the glucose-stimulated insulin secretion, intracellular insulin gene expression, and intracellular ATP level. The Park2-depleted β-cells also exhibited increased mitochondrial fragmentation and ROS production and decreased mitochondrial membrane potential. Both population-based statistical evaluation and experimental evidence demonstrated a fundamental role of the PARK2 gene in the maintenance of β-cell function.

  4. 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

  5. Variable-target-function and build-up procedures for the calculation of protein conformation. Application to bovine pancreatic trypsin inhibitor using limited simulated nuclear magnetic resonance data.

    PubMed

    Vásquez, M; Scheraga, H A

    1988-02-01

    An implementation of the variable-target-function procedure, first introduced by Braun and Go [W. Braun and N. Go, J. Mol. Biol. 186, 611-626 (1985)], has been used to generate conformations of the small protein bovine pancreatic trypsin inhibitor (BPTI), given a limited set of simulated data that could be obtained by nuclear magnetic resonance (NMR) techniques. A hybrid strategy was also used to calculate conformations of BPTI, given the same information. In the hybrid strategy, low-energy structures of medium-size fragments (decapeptides) of BPTI were generated using the variable-target-function method, followed by restrained energy optimization. The low-energy conformations were used as a basis to build up the complete fifty-eight-residue BPTI molecule. By using the variable-target-function approach, in which energy considerations were not introduced until full conformations of the entire BPTI molecule had been generated, it was not possible to obtain calculated structures with rms deviations from the X-ray conformation of less than 1.6 A for the alpha-carbons. On the other hand, with the hybrid strategy, which involved the consideration of realistic energy terms in the early stages of the calculations, it was possible to calculate low-energy conformations of BPTI with rms deviations from the X-ray structure of 1.06 to 1.50 A for the alpha-carbons. When the rms deviations were computed along the amino acid sequence, it was found that there was a good correlation between deviations among the calculated structures and deviations from the X-ray structure.

  6. 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...

  7. 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 ...

  8. 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 ...

  9. Hypothyroidism in utero stimulates pancreatic beta cell proliferation and hyperinsulinaemia in the ovine fetus during late gestation.

    PubMed

    Harris, Shelley E; De Blasio, Miles J; Davis, Melissa A; Kelly, Amy C; Davenport, Hailey M; Wooding, F B Peter; Blache, Dominique; Meredith, David; Anderson, Miranda; Fowden, Abigail L; Limesand, Sean W; Forhead, Alison J

    2017-01-31

    Development of pancreatic beta cell mass before birth is essential for normal growth of the fetus and for long-term control of carbohydrate metabolism in postnatal life. Thyroid hormones are also important regulators of fetal growth, and the present study tested the hypotheses that thyroid hormones promote beta cell proliferation in the fetal ovine pancreatic islets, and that growth retardation in hypothyroid fetal sheep is associated with reductions in pancreatic beta cell mass and circulating insulin concentration in utero. Organ growth and pancreatic islet cell proliferation and mass were examined in sheep fetuses following removal of the thyroid gland in utero. The effects of T3 , insulin and leptin on beta cell proliferation rates were determined in isolated fetal ovine pancreatic islets in vitro. Hypothyroidism in the sheep fetus resulted in an asymmetric pattern of organ growth, pancreatic beta cell hyperplasia, and elevated plasma insulin and leptin concentrations. In pancreatic islets isolated from intact fetal sheep, beta cell proliferation in vitro was reduced by T3 in a dose-dependent manner and increased by insulin at high concentrations only. Leptin induced a bimodal response whereby beta cell proliferation was suppressed at the lowest, and increased at the highest, concentrations. Therefore, proliferation of beta cells isolated from the ovine fetal pancreas is sensitive to physiological concentrations of T3 , insulin and leptin. Alterations in these hormones may be responsible for the increased beta cell proliferation and mass observed in the hypothyroid sheep fetus and may have consequences for pancreatic function in later life. This article is protected by copyright. All rights reserved.

  10. Evaluation of Matrix Metalloproteinase 7 in Plasma and Pancreatic Juice as a Biomarker for Pancreatic Cancer

    PubMed Central

    Kuhlmann, Koert F.D.; van Till, J.W. Olivier; Boermeester, Marja A.; de Reuver, Philip R.; Tzvetanova, Iva D.; Offerhaus, G. Johan A.; ten Kate, Fiebo J.W.; Busch, Olivier R.C.; van Gulik, Thomas M.; Gouma, Dirk J.; Crawford, Howard C.

    2015-01-01

    Differentiating between periampullary carcinoma and chronic pancreatitis with an inflammatory mass is difficult. Consequently, 6% to 9% of pancreatic resections for suspected carcinoma are done inappropriately for chronic pancreatitis. Here, we test if matrix metalloproteinase 7 (MMP-7), a secreted protease frequently expressed in pancreatic carcinoma, can be measured in plasma, pancreatic, and duodenal juice, and if it can distinguish between periampullary carcinoma and chronic pancreatitis. Ninety-four patients who underwent pancreatic surgery for a (peri)pancreatic neoplasm (n = 63) or chronic pancreatitis (n = 31) were analyzed. Median plasma MMP-7 levels were significantly higher in carcinoma (1.95 ng/mL; interquartile range, 0.81–3.22 ng/mL) compared with chronic pancreatitis and benign disease (0.83 ng/mL; interquartile range, 0.25–1.21 ng/mL; P < 0.01). MMP-7 levels in pancreatic juice were higher, although not significantly, in carcinoma (62 ng/mg protein; interquartile range, 18–241 ng/mg protein) compared with chronic pancreatitis and benign disease (23 ng/mg protein; interquartile range, 8.5–99 ng/mg protein; P = 0.17). MMP-7 levels in duodenal juice were universally low. At an arbitrary cutoff of 1.5 ng/mL in plasma, positive and negative predictive values were 83% and 57%, respectively, values comparable to those of today’s most common pancreatic tumor marker, carbohydrate antigen 19-9 (CA19-9; 83% and 53%, respectively). Positive and negative likelihood ratios for plasma MMP-7 were 3.35 and 0.52, respectively. The area under the receiver operating characteristic curve for MMP-7 was 0.73 (95% confidence interval, 0.63–0.84) and for CA19-9, 0.75 (95% confidence interval, 0.64–0.85). Combined MMP-7 and CA19-9 assessment gave a positive predictive value of 100%. Thus, plasma MMP-7 levels discriminated between patients with carcinoma and those with chronic pancreatitis or benign disease. The diagnostic accuracy of plasma MMP-7 alone is not

  11. Managing acute and chronic pancreatitis.

    PubMed

    Skipworth, James R A; Shankar, Arjun; Pereira, Stephen P

    2010-10-01

    Pancreatitis may be acute or chronic. Although both can be caused by similar aetiologies, they tend to follow distinct natural histories. Around 80% of acute pancreatitis (AP) diagnoses occur secondary to gallstone disease and alcohol misuse. AP is commonly associated with sudden onset of upper abdominal pain radiating to the back that is usually severe enough to warrant the patient seeking urgent medical attention. Onset of pain may be related to a recent alcohol binge or rich, fatty meal. The patient may appear unwell, be tachycardic and have exquisite tenderness in the upper abdomen. Overall, 10-25% of AP episodes are classified as severe, leading to an associated mortality rate of 7.5%. Disease severity is best predicted from a number of clinical scoring systems which can be applied at diagnosis in association with repeated clinical assessment, measurement of acute inflammatory markers, and CT. All patients with suspected AP should be referred urgently. Chronic pancreatitis (CP) follows continued, repetitive or sustained injury to the pancreas and 70% of diagnoses occur secondary to alcohol abuse. The characteristic presenting feature of CP is insidious progression of chronic, severe, upper abdominal pain, radiating to the back, caused by a combination of progressive pancreatic destruction, inflammation and duct obstruction. Signs and symptoms include weight loss and steatorrhoea and later on diabetes. CP patients may also present with recurrent episodes mimicking AP, both symptomatically and metabolically. Diagnosis of CP should be based on symptom profile, imaging and assessment of exocrine and endocrine pancreatic function. CT should be the first-line imaging investigation.

  12. Delayed motor function and results of vestibular function tests in children with inner ear anomalies.

    PubMed

    Tsuzuku, T; Kaga, K

    1992-05-01

    The relation between the results of vestibular function tests and gross motor development was examined in 4 children with inner ear anomalies. CT scans demonstrated the absence of lateral semicircular canals in both ears in all 4 cases. None responded to caloric stimulation using 40 ml of icewater. In contrast, the damped rotation test elicited per-rotatory nystagmus in all cases. Per-rotatory nystagmus was provoked in only two cases by the Bárány rotation test. Development of gross motor function, especially independent walking, was more delayed in the two children in whom the Bárány rotation test failed to elicit per-rotatory nystagmus.

  13. Differential functioning of Bender Visual-Motor Gestalt Test items.

    PubMed

    Sisto, Fermino Fernandes; Dos Santos, Acácia Aparecida Angeli; Noronha, Ana Paula Porto

    2010-02-01

    Differential Item Functioning (DIF) refers to items that do not function the same way for comparable members of different groups. The present study focuses on analyzing and classifying sex-related differential item functioning in the Bender Visual-Motor Gestalt Test. Subjects were 1,052 children attending public schools (513 boys, 539 girls, ages 6-10 years). The protocols were scored using the Bender Graduated Scoring System, which evaluates only the distortion criterion using the Rasch logistic response model. The scoring system fit the Rasch model, although two items were found to be biased by sex. When analyzing differential functioning of items for boys and girls separately, the number of differentially functioning items was equal.

  14. 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.

  15. 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.

  16. Differential Item Functioning: Performance by Sex on Reading Comprehension Tests.

    ERIC Educational Resources Information Center

    Gafni, Naomi

    Items in the verbal (Hebrew and English) sections of the Psychometric Entrance Test (PET) administered for university admission in Israel were studied for differential item functioning (DIF) between the sexes. Analyses were conducted for 4,354 males and 4,901 females taking Form 3 of the PET in April 1984, and 3,786 males and 3,815 females taking…

  17. Effect of Differential Item Functioning on Test Equating

    ERIC Educational Resources Information Center

    Kabasakal, Kübra Atalay; Kelecioglu, Hülya

    2015-01-01

    This study examines the effect of differential item functioning (DIF) items on test equating through multilevel item response models (MIRMs) and traditional IRMs. The performances of three different equating models were investigated under 24 different simulation conditions, and the variables whose effects were examined included sample size, test…

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

    ERIC Educational Resources Information Center

    Beck, Danielle M.; Schaefer, Catherine; Pang, Karen; Carlson, Stephanie M.

    2011-01-01

    Research suggests that executive function (EF) may distinguish between children who are well- or ill-prepared for kindergarten; however, little is known about the test-retest reliability of measures of EF for children. We aimed to establish a battery of EF measures that are sensitive to both development and individual differences across the…

  19. Investigation of Functional Working Memory in the Reading Span Test.

    ERIC Educational Resources Information Center

    Tirre, William C.; Pena, Carmen M.

    1992-01-01

    Two experiments with approximately 377 newly enlisted Air Force personnel and 182 college students investigated the validity of a reading span test combining a knowledge verification task with a word memorization task. Results support the hypothesis that word recall reflects the amount of working memory functional in reading. (SLD)

  20. Testing for Differential Item Functioning with Measures of Partial Association

    ERIC Educational Resources Information Center

    Woods, Carol M.

    2009-01-01

    Differential item functioning (DIF) occurs when an item on a test or questionnaire has different measurement properties for one group of people versus another, irrespective of mean differences on the construct. There are many methods available for DIF assessment. The present article is focused on indices of partial association. A family of average…

  1. Effects of physical activity on exercise tests and respiratory function

    PubMed Central

    Cheng, Y; Macera, C; Addy, C; Sy, F; Wieland, D; Blair, S

    2003-01-01

    Background: Exercise is an important component of pulmonary rehabilitation for patients with chronic lung disease. Objective: To explore the role of physical activity in maintaining cardiac and respiratory function in healthy people. Methods: Cardiorespiratory fitness was measured by a maximal treadmill test (MTT), and respiratory function was tested by spirometry. The cross sectional study included data from 24 536 healthy persons who were examined at the Cooper Clinic between 1971 and 1995; the longitudinal study included data from 5707 healthy persons who had an initial visit between 1971 and 1995 and a subsequent visit during the next five years. All participants were aged 25–55 years and completed a cardiorespiratory test and a medical questionnaire. Results: In the cross sectional study, after controlling for covariates, being active and not being a recent smoker were associated with better cardiorespiratory fitness and respiratory function in both men and women. In the follow up study, persons who remained or became active had better MTT than persons who remained or became sedentary. Men who remained active had higher forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) than the other groups. Smoking was related to lower cardiorespiratory fitness and respiratory function. Conclusions: Physical activity and non-smoking or smoking cessation is associated with maintenance of cardiorespiratory fitness. Change in physical activity habits is associated with change in cardiorespiratory fitness, but respiratory function contributed little to this association during a five year follow up. PMID:14665592

  2. 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

  3. Using Operational Analysis to Improve Access to Pulmonary Function Testing

    PubMed Central

    Ip, Ada; Asamoah-Barnieh, Raymond; Bischak, Diane P.; Davidson, Warren J.; Flemons, W. Ward; Pendharkar, Sachin R.

    2016-01-01

    Background. Timely pulmonary function testing is crucial to improving diagnosis and treatment of pulmonary diseases. Perceptions of poor access at an academic pulmonary function laboratory prompted analysis of system demand and capacity to identify factors contributing to poor access. Methods. Surveys and interviews identified stakeholder perspectives on operational processes and access challenges. Retrospective data on testing demand and resource capacity was analyzed to understand utilization of testing resources. Results. Qualitative analysis demonstrated that stakeholder groups had discrepant views on access and capacity in the laboratory. Mean daily resource utilization was 0.64 (SD 0.15), with monthly average utilization consistently less than 0.75. Reserved testing slots for subspecialty clinics were poorly utilized, leaving many testing slots unfilled. When subspecialty demand exceeded number of reserved slots, there was sufficient capacity in the pulmonary function schedule to accommodate added demand. Findings were shared with stakeholders and influenced scheduling process improvements. Conclusion. This study highlights the importance of operational data to identify causes of poor access, guide system decision-making, and determine effects of improvement initiatives in a variety of healthcare settings. Importantly, simple operational analysis can help to improve efficiency of health systems with little or no added financial investment. PMID:27445545

  4. Duct Drainage Alone is Sufficient in the Operative Management of Pancreatic Pseudocyst in Patients With Chronic Pancreatitis

    PubMed Central

    Nealon, William H.; Walser, Eric

    2003-01-01

    Objective To test a hypothesis that definitive management of pseudocyst associated with chronic pancreatitis is predicated on addressing pancreatic ductal anatomy. Summary Background Data The authors have previously confirmed the impact of pancreatic ductal anatomic abnormalities on the success of percutaneous drainage of pancreatic pseudocyst. The authors have further defined a system to categorize the pancreatic ductal abnormalities that can be seen with pancreatic pseudocyst. The authors have published, as have others, the usefulness of defining ductal anatomy when managing pancreatic pseudocysts associated with chronic pancreatitis. Methods Beginning in 1985, all patients with pseudocyst who were candidates for intervention (operative, percutaneous, or endoscopic) have undergone endoscopic retrograde cholangiopancreatography (ERCP). An associated diagnosis of chronic pancreatitis was established by means of ERCP findings. Patients were candidates for longitudinal pancreaticojejunostomy (LPJ) if they had a pancreatic ductal diameter greater than 7 mm. In a nonrandomized fashion, patients were managed with either combined simultaneous LPJ and pseudocyst drainage or with LPJ alone. Results Two hundred fifty-three patients with pseudocyst have been evaluated. Among these there have been 103 patients with chronic pancreatitis and main pancreatic duct (MPD) dilatation (>7 mm). Among these 103 patients, 56 underwent combined LPJ/pseudocyst drainage and 47 had LPJ alone. Compared to combined LPJ/pseudocyst drainage, the patients undergoing LPJ alone had a shorter operative time, slightly less transfusion requirement, slightly reduced length of hospital stay, and slightly reduced complication rate. Long-term pain relief was achieved in 90%, and pseudocyst recurrence was less than 1%. Rates of each of these long-term outcomes were nearly incidental among the two groups. Conclusions Ductal drainage alone (LPJ) is sufficient in patients with chronic pancreatitis (MPD > 7

  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. 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

  7. Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells

    NASA Astrophysics Data System (ADS)

    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

    2016-06-01

    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.

  8. Hypermutation In Pancreatic Cancer.

    PubMed

    Humphris, Jeremy L; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J; Johns, Amber L; McKay, Skye; Chang, David K; Miller, David K; Pajic, Marina; Kassahn, Karin S; Quinn, Michael C J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Stone, Andrew; Wilson, Peter J; Anderson, Matthew; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Mead, Ronald S; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Nagrial, Adnan M; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Rooman, Ilse; Giry-Laterriere, Marc; Samra, Jaswinder S; Kench, James G; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; McKay, Colin J; Carter, C Ross; Dickson, Euan J; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Morton, Jennifer P; Sansom, Owen J; Grützmann, Robert; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Rusev, Borislav; Corbo, Vincenzo; Salvia, Roberto; Cataldo, Ivana; Tortora, Giampaolo; Tempero, Margaret A; Hofmann, Oliver; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Gill, Anthony J; Pearson, John V; Grimmond, Sean M; Waddell, Nicola; Biankin, Andrew V

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.

  9. Examining the Relationship between Differential Item Functioning and Differential Test Functioning

    ERIC Educational Resources Information Center

    Pae, Tae-Il; Park, Gi-Pyo

    2006-01-01

    The present study utilized both the IRT-LR (item response theory likelihood ratio) and a series of CFA (confirmatory factor analysis) multi-sample analyses to systematically examine the relationships between DIF (differential item functioning) and DTF (differential test functioning) with a random sample of 15 000 Korean examinees. Specifically,…

  10. 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…

  11. Autonomic function testing: an important diagnostic test for patients with syncope.

    PubMed

    Jones, Pearl K; Gibbons, Christopher H

    2015-10-01

    Syncope is a common problem with a large differential diagnosis. The initial history and physical examination often provide initial clues; however, some cases warrant further testing to determine the underlying cause. Autonomic function testing is a safe way to evaluate patients with syncope further, and to assess their parasympathetic and sympathetic nervous systems. Autonomic testing can help to diagnose several conditions, including orthostatic hypotension, delayed orthostatic hypotension, postural tachycardia syndrome and neutrally mediated syncope. Thus, when the cause of syncope is unclear, autonomic testing can help to assess the autonomic nervous system, stratify the risk of future episodes and to guide treatment decisions.

  12. [Neurological lower torso function test. A new assessment].

    PubMed

    Merkert, J; Butz, S; Nieczaj, R; Steinhagen-Thiessen, E; Eckardt, R

    2013-02-01

    The neurological lower torso function test was developed in addition to the Berg Balance Scale as an assessment for diagnosis and follow-up of lower torso stability and functioning in neurological patients, used for example in subjects in the early rehabilitation phase or still showing low motoric recovery after suffering a stroke. Due to the ground effect for changes in severely affected neurological patients, other tests currently available do not provide an adequate level of sensitivity. The neurological function test was integrated into the study "Combined whole body vibration and balance training using Vibrosphere" with 66 inpatient/partial inpatient neurological subjects ≥ 60 years. Based on six tasks, a qualitative assessment of the selective function of movement and posture tone of the lower extremity, the muscular system around the hip, and the lower torso are performed. Analogous to the Berg Balance Scale, a 5 point scale is used. It shows a high degree of reliability and responsiveness and can be performed with little effort of time and personnel.

  13. Autoimmune pancreatitis mimicking Klatskin tumour on radiology.

    PubMed

    Hadi, Yousaf Bashir; Sohail, Abdul Malik Amir Humza; Haider, Zishan

    2015-04-09

    Autoimmune pancreatitis (AIP) is categorised into two distinct types, AIP type 1 and 2. Although there can be multisystem involvement, rarely, the cholangitis associated with AIP can present radiologically in a manner similar to that of Klatskin tumour. We present the case of a 65-year-old man who was almost misdiagnosed with a Klatskin tumour because of the similarity in radiological features of the two aforementioned clinical entities. The patient presented with a history of jaundice, pruritus and abdominal pain, and work up showed deranged liver function tests, elevated cancer antigen 19-9 levels and positive antinuclear antibodies. CT scan of the abdomen showed findings suggestive of Klatskin tumour but due to diffuse enlargement of the pancreas and surrounding low-attenuation halo found on a closer review, a diagnosis of AIP was performed. The patient was started on standard corticosteroid therapy and responded well, with complete resolution of the radiological findings.

  14. Treatment of Pancreatic Cancer with Pharmacological Ascorbate.

    PubMed

    Cieslak, John A; Cullen, Joseph J

    2015-01-01

    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.

  15. β-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions

    PubMed Central

    Zhu, Lu; Almaça, Joana; Dadi, Prasanna K.; Hong, Hao; Sakamoto, Wataru; Rossi, Mario; Lee, Regina J.; Vierra, Nicholas C.; Lu, Huiyan; Cui, Yinghong; McMillin, Sara M.; Perry, Nicole A.; Gurevich, Vsevolod V.; Lee, Amy; Kuo, Bryan; Leapman, Richard D.; Matschinsky, Franz M.; Doliba, Nicolai M.; Urs, Nikhil M.; Caron, Marc G.; Jacobson, David A.; Caicedo, Alejandro; Wess, Jürgen

    2017-01-01

    β-arrestins are critical signalling molecules that regulate many fundamental physiological functions including the maintenance of euglycemia and peripheral insulin sensitivity. Here we show that inactivation of the β-arrestin-2 gene, barr2, in β-cells of adult mice greatly impairs insulin release and glucose tolerance in mice fed with a calorie-rich diet. Both glucose and KCl-induced insulin secretion and calcium responses were profoundly reduced in β-arrestin-2 (barr2) deficient β-cells. In human β-cells, barr2 knockdown abolished glucose-induced insulin secretion. We also show that the presence of barr2 is essential for proper CAMKII function in β-cells. Importantly, overexpression of barr2 in β-cells greatly ameliorates the metabolic deficits displayed by mice consuming a high-fat diet. Thus, our data identify barr2 as an important regulator of β-cell function, which may serve as a new target to improve β-cell function. PMID:28145434

  16. Functional diversity, soil features and community functioning: a test in a cerrado site.

    PubMed

    Freitas, J R; Cianciaruso, M V; Batalha, M A

    2012-08-01

    Community functioning may be affected by functional diversity, which measures the extent of complementarity in resource use. We tested whether there was a relationship between functional diversity of woody species and community functioning on a fine scale, using FD as a measure of functional diversity and litter decomposition rate as a surrogate for community functioning. We measured eight functional traits from a woodland cerrado community in southeastern Brazil. Then, we tested the correlation between FD and the decomposition rate taking into account differences in soil features and between decomposition rate and each trait separately. The decomposition rate was related to the aluminium and phosphorus concentration in soil, but not to FD, pointing out that functional diversity was not a good predictor of community functioning. There was a non-significant relationship between FD and the decomposition rate even when we considered each trait separately. Most studies in the relationships between biodiversity and community functioning on fine scales were carried out by experimental manipulation of diversity and in temperate regions. We carried out this fine scale study as a mensurative experiment and in a tropical savanna. Our findings indicated that the relationship between biodiversity and community functioning is not as straightforward as usually assumed.

  17. 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

  18. Analysis of the pancreatic low molecular weight proteome in an animal model of acute pancreatitis.

    PubMed

    Lassout, Olivier; Pastor, Catherine M; Fétaud-Lapierre, Vanessa; Hochstrasser, Denis F; Frossard, Jean-Louis; Lescuyer, Pierre

    2010-09-03

    We used a peptidomic approach for the analysis of the low molecular weight proteome in rat pancreatic tissue extracts. The goal was to develop a method that allows identifying endogenous peptides produced in the pancreas in the course of acute pancreatitis. The workflow combines peptides enrichment by centrifugal ultrafiltration, fractionation by isoelectric focusing, and LC-MS/MS analysis without prior enzymatic digestion. The method was assessed on pancreatic extracts from 3 rats with caerulein-induced pancreatitis and 3 healthy controls. A qualitative analysis of the peptide patterns obtained from the different samples was performed to determine the main biological processes associated to the identified peptides. Comparison of peptidomic and immunoblot data for alpha-tubulin, beta-tubulin and coatomer gamma showed that the correlation between the number of identified peptides and the protein abundance was variable. Nevertheless, peptidomic analysis highlighted inflammatory and stress proteins, which peptide pattern was related to acute pancreatitis pathobiology. For these proteins, the higher number of peptides in pancreatitis samples reflected an increase in protein abundance. Moreover, for murinoglobulin-1 or carboxypeptidase B, peptide pattern could be related to protein function. These data suggest that peptidomic analysis is a complementary approach to proteomics for investigating pathobiological processes involved in acute pancreatitis.

  19. Patient and Societal Value Functions for the Testing Morbidities Index

    PubMed Central

    Swan, John Shannon; Kong, Chung Yin; Lee, Janie M.; Akinyemi, Omosalewa; Halpern, Elkan F.; Lee, Pablo; Vavinskiy, Sergey; Williams, Olubunmi; Zoltick, Emilie S.; Donelan, Karen

    2013-01-01

    Background We developed preference-based and summated scale scoring for the Testing Morbidities Index (TMI) classification, which addresses short-term effects on quality of life from diagnostic testing before, during and after a testing procedure. Methods The two TMI value functions utilize multiattribute value techniques; one is patient-based and the other has a societal perspective. 206 breast biopsy patients and 466 (societal) subjects informed the models. Due to a lack of standard short-term methods for this application, we utilized the visual analog scale (VAS). Waiting trade-off (WTO) tolls provided an additional option for linear transformation of the TMI. We randomized participants to one of three surveys: the first derived weights for generic testing morbidity attributes and levels of severity with the VAS; a second developed VAS values and WTO tolls for linear transformation of the TMI to a death-healthy scale; the third addressed initial validation in a specific test (breast biopsy). 188 patients and 425 community subjects participated in initial validation, comparing direct VAS and WTO values to the TMI. Alternative TMI scoring as a non-preference summated scale was included, given evidence of construct and content validity. Results The patient model can use an additive function, while the societal model is multiplicative. Direct VAS and the VAS-scaled TMI were correlated across modeling groups (r=0.45 to 0.62) and agreement was comparable to the value function validation of the Health Utilities Index 2. Mean Absolute Difference (MAD) calculations showed a range of 0.07–0.10 in patients and 0.11–0.17 in subjects. MAD for direct WTO tolls compared to the WTO-scaled TMI varied closely around one quality-adjusted life day. Conclusions The TMI shows initial promise in measuring short-term testing-related health states. PMID:23689044

  20. Real-Time Fall Risk Assessment Using Functional Reach Test

    PubMed Central

    Williams, Brian; Allen, Brandon; True, Hanna; Cho, Jin; Harris, Austin; Fell, Nancy

    2017-01-01

    Falls are common and dangerous for survivors of stroke at all stages of recovery. The widespread need to assess fall risk in real time for individuals after stroke has generated emerging requests for a reliable, inexpensive, quantifiable, and remote clinical measure/tool. In order to meet these requests, we explore the Functional Reach Test (FRT) for real-time fall risk assessment and implement the FRT function in mStroke, a real-time and automatic mobile health system for poststroke recovery and rehabilitation. mStroke is designed, developed, and delivered as an Application (App) running on a hardware platform consisting of an iPad and one or two wireless body motion sensors based on different mobile health functions. The FRT function in mStroke is extensively tested on healthy human subjects to verify its concept and feasibility. Preliminary performance will be presented to justify the further exploration of the FRT function in mStroke through clinical trials on individuals after stroke, which may guide its ubiquitous exploitation in the near future. PMID:28167961

  1. 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

  2. Lipase Test

    MedlinePlus

    ... known as: LPS Formal name: Lipase Related tests: Amylase , Trypsin , Trypsinogen At a Glance Test Sample The ... lipase is most often used, along with an amylase test , to help diagnose and monitor acute pancreatitis . ...

  3. 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

  4. 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

  5. Lymphoplasmacytic sclerosing pancreatitis (autoimmune pancreatitis): evaluation with multidetector CT.

    PubMed

    Kawamoto, Satomi; Siegelman, Stanley S; Hruban, Ralph H; Fishman, Elliot K

    2008-01-01

    Lymphoplasmacytic sclerosing pancreatitis is a form of chronic pancreatitis characterized by a mixed inflammatory infiltrate that centers on the pancreatic ducts. It is a cause of benign pancreatic disease that can clinically mimic pancreatic cancer. Preoperative detection of lymphoplasmacytic sclerosing pancreatitis is important because patients usually respond to steroid therapy. Patients with lymphoplasmacytic sclerosing pancreatitis are often referred for computed tomography (CT) when they are suspected of having a pancreatic or biliary neoplasm; therefore, it is important to search for potential findings suggestive of lymphoplasmacytic sclerosing pancreatitis when typical findings of a pancreatic or biliary neoplasm are not found. Typical CT findings include diffuse or focal enlargement of the pancreas without dilatation of the main pancreatic duct. Focal enlargement is most commonly seen in the head of the pancreas, and the involved pancreas on contrast material-enhanced CT images may be iso-attenuating relative to the rest of the pancreas, or hypo-attenuating, especially during the early postcontrast phase. Thickening and contrast enhancement of the wall of the common bile duct and gallbladder may reflect inflammatory infiltrate and fibrosis associated with lymphoplasmacytic sclerosing pancreatitis. There are several features seen at CT that may help to differentiate lymphoplasmacytic sclerosing pancreatitis from pancreatic cancer, such as diffuse enlargement of the pancreas with minimal peripancreatic stranding in patients with obstructive jaundice, an absence of significant pancreatic atrophy, and an absence of significant main pancreatic duct dilatation. When these findings are encountered, clinical, other imaging, and serologic data should be evaluated.

  6. 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.

  7. 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

  8. Knowledge Gaps in Rodent Pancreas Biology: Taking Human Pluripotent Stem Cell-Derived Pancreatic Beta Cells into Our Own Hands.

    PubMed

    Santosa, Munirah Mohamad; Low, Blaise Su Jun; Pek, Nicole Min Qian; Teo, Adrian Kee Keong

    2015-01-01

    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.

  9. CFTR: A new horizon in the pathomechanism and treatment of pancreatitis

    PubMed Central

    Hegyi, Péter; Wilschanski, Michael; Muallem, Shmuel; Lukacs, Gergely; Sahin-Tóth, Miklós; Uc, Aliye; Gray, Michael A.; Rakonczay, Zoltán; Maléth, József

    2017-01-01

    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

  10. 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.

  11. Contraceptive pills and acute pancreatitis.

    PubMed

    Mehrotra, T N; Mital, H S; Gupta, S K

    1981-06-01

    This article reports a case of acute pancreatitis in a patient taking the oral contraceptive pill. A 32 year old mother had been on combined contraceptive pills since 1975. In 1978 she started having upper abdominal and retrosternal pain. She became critically ill with peripheral circulatory collapse, dyspnoea and cyanosis. A superficial thrombophlebitis was noted on the medial aspect of the right thigh. The diagnosis of pancreatitis was considered with history of recurrent abdominal pain. After several tests and supportive therapy (intravenous fluids, antibiotics, steriods), the woman started showing improvements in 48 hours and recovered in 10 days. This case differs from previously described cases in that the cholesterol and triglyceride levels were normal. The hypoglycemia has not been described previously.

  12. 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

  13. 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

  14. Testing Changes in Visual Function Due to Orbital Environment

    DTIC Science & Technology

    1984-01-01

    describes a device submitted by the AF Aerospace Medical Research Laboratory for inclusion aboard several NASA Shuttle Flights, in an attempt to detect...Duntley Tests ROCET P0BL 4 VISUAL FUNCTION TESTER [ODEL I (VFT-1) 5 Description Usage Critical Fusion Frequency Stereopsis Snellen Acuity Resolution...self-contained, draw no power from the Shuttle, and must meet stringent NASA technical, safety and acceptance standards. This report describes the

  15. Lymphoplasmacytic sclerosing pancreatitis.

    PubMed

    Plaza, Jose Antonio; Colonna, Jorge; Vitellas, Kenneth M; Frankel, Wendy L

    2005-10-01

    Lymphoplasmacytic sclerosing pancreatitis is a rare entity that has been described under many different names and constitutes a diagnostic challenge as it may simulate a neoplastic process. Herein, we report a case of a 61-year-old woman who presented to our institution complaining of left flank pain and was found to have normal levels of amylase and lipase. An abdominal magnetic resonance image showed thickening of the pancreatic tail and compression of the pancreatic duct. The radiographic differential included both chronic pancreatitis and a neoplastic process. She underwent an exploratory laparotomy, during which a pancreatectomy and splenectomy were performed. Grossly, the pancreas contained a yellowish white, firm homogeneous mass measuring 6.5 x 3.3 x 2.9 cm involving the entire pancreatic tail and hilum of the spleen. Histologically, pancreatic sections showed extensive fibrosis admixed with an inflammatory infiltrate. This infiltrate was composed mainly of lymphocytes with multiple germinal centers, as well as plasma cells and eosinophils that surrounded pancreatic ducts and extended into the peripancreatic adipose tissue. No malignancy was identified, and the process was diagnosed as lymphoplasmacytic sclerosing pancreatitis.

  16. Absence of cardiovascular autonomic dysfunction and vagal pancreatic impairment in idiopathic achalasia of the oesophagus.

    PubMed

    Herreros, B; Ascaso, J F; Mora, F; Costa, A J; Sanchiz, V; Minguez, M; Benages, A

    2007-08-01

    Extra-oesophageal autonomic dysfunction in idiopathic achalasia is not well documented, due to contradictory results reported. We aimed to study the cardiovascular and pancreatic autonomic function in patients with idiopathic achalasia. Thirty patients with idiopathic achalasia (16M/14F; 34.5 +/- 10.8 years) and 30 healthy volunteers (13M/17F; 34.8 +/- 10.7 years) were prospectively studied. Age >60 years and conditions affecting results of autonomic evaluation were excluded. Both groups underwent the sham feeding test and plasmatic levels of pancreatic polypeptide (PP) were determined by radioimmunoassay (basal, at 5, 10, 20 and 30 min). Cardiovascular parasympathetic (deep breathing, standing, Valsalva) and sympathetic function (postural decrease of systolic blood pressure, Handgrip test) were assessed. Statistical comparison of basal and increase levels of PP and parasympathetic/sympathetic cardiovascular parameters was performed between groups. Basal levels of PP were similar in controls and patients and maximum increase of PP during sham feeding test. A similar rate of abnormal cardiovascular tests was found between groups (P > 0.05). E/I ratio was the mostly impaired parameter (patients: 36.7% vs controls: 20%, P = 0.15, chi-squared test). Autonomic cardiovascular tests and pancreatic response to vagal stimulus are not impaired in patients with primary achalasia of the oesophagus.

  17. Six-year follow-up of pancreatic β cell function in adults with latent autoimmune diabetes

    PubMed Central

    Yang, Lin; Zhou, Zhi-Guang; Huang, Gan; Ouyang, Ling-Li; Li, Xia; Yan, Xiang

    2005-01-01

    AIM: To investigate the characteristics of the progression of islet β cell function in Chinese latent autoimmune diabetes in adult (LADA) patients with glutamic acid decarboxylase antibody (GAD-Ab) positivity, and to explore the prognostic factors for β cell function. METHODS: Forty-five LADA patients with GAD-Ab positivity screened from phenotypic type 2 diabetic (T2DM) patients and 45 T2DM patients without GAD-Ab matched as controls were followed-up every 6 mo. Sixteen patients in LADA1 and T2DM1 groups respectively have been followed-up for 6 years, while 29 patients in LADA2 and T2DM2 groups respectively for only 1.5 years. GAD-Ab was determined by radioligand assay, and C-peptides (CP) by radioimmune assay. RESULTS: The percentage of patients whose fasting CP (FCP) decreased more than 50% compared with the baseline reached to 25.0% at 1.5th year in LADA1 group, and FCP level decreased (395.8±71.5 vs 572.8±72.3 pmol/L, P<0.05) at 2.5th year and continuously went down to the end of follow-up. No significant changes of the above parameters were found in T2DM1 group. The average decreased percentages of FCP per year in LADA and T2DM patients were 15.8% (4.0-91.0%) and 5.2% (-3.5 to 35.5%, P = 0.000) respectively. The index of GAD-Ab was negatively correlated with the FCP in LADA patients (rs = -0.483, P = 0.000). The decreased percentage of FCP per year in LADA patients were correlated with GAD-Ab index, body mass index (BMI) and age at onset (rs = 0.408, -0.301 and -0.523 respectively, P<0.05). Moreover, GAD-Ab was the only risk factor for predicting β cell failure in LADA patients (B = 1.455, EXP (B) = 4.283, P = 0.023). CONCLUSION: The decreasing rate of islet β cell function in LADA, being highly heterogeneous, is three times that of T2DM patients. The titer of GAD-Ab is an important predictor for the progression of islet β cell function, and age at onset and BMI could also act as the predictors. PMID:15902725

  18. Pancreatic Satellite Cells Derived Galectin-1 Increase the Progression and Less Survival of Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Gao, Jun; Wang, Sen; Ye, Nianyuan; Li, Ping; Gao, Sujun; Miao, Yi; Wang, Daorong; Jiang, Kuirong

    2014-01-01

    Background Galectin-1, a member of carbohydrate-binding proteins with a polyvalent function on tumor progression, was found strongly expressed in pancreatic satellite cells (PSCs), which partner in crime with cancer cells and promote the development of pancreatic ductal adenocarcinoma (PDAC). We evaluated the effects of PSCs derived Galectin-1 on the progression of PDAC, as well as the tumor establishment and development in mouse xenografts. Methods The relationship between immunohistochemistry staining intensity of Galectin-1 and clinicopathologic variables were assessed in 66 PDAC tissues, 18 chronic pancreatitis tissues and 10 normal controls. The roles of PSCs isolated from PDAC and normal pancreas on the proliferative activity, MMP2 and MMP9 expression, and the invasion of CFPAC-1 in the co-cultured system, as well as on the tumor establishment and development in mouse xenografts by mixed implanting with CFPAC-1 subcutaneously were evaluated. Results Galectin-1 expression was gradually increased from normal pancreas (negative), chronic pancreatitis (weak) to PDAC (strong), in which Galectin-1 expression was also increased from well, moderately to poorly differentiated PDAC. Galectin-1 staining intensity of pancreatic cancer tissue was associated with increase in tumor size, lymph node metastasis, perineural invasion and differentiation and UICC stage, and served as the independent prognostic indicator of poor survival of pancreatic cancer. In vitro and in vivo experiments indicated that TGF-β1 upregulated Galectin-1 expression in PSCs, which could further promotes the proliferative activity, MMP2 and MMP9 expression, and invasion of pancreatic cancer cells, as well as the tumor establishment and growth. Conclusion Galectin-1 expression in stromal cells of pancreatic cancer suggests that this protein plays a role in the promotion of cancer cells invasion and metastasis and provides a therapeutic target for the treatment of pancreatic cancer. PMID:24595374

  19. 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

  20. Survival and B-cell function of neonatal pig pancreatic islet-like cell clusters in an extracellular matrix.

    PubMed

    Ohgawara, H; Mochizuki, N; Karibe, S; Omori, Y

    1991-11-01

    Islet-like cell clusters (ICCs), formed from single cells of pig pancreas in suspension culture, were embedded in an extracellular matrix. It was recently reported that nicotinamide prevented dissolution of the extracellular matrix by the ICCs. In this experiment, various conditions for embedded culture of ICCs in an extracellular matrix were studied, in an attempt to maintain the function as well as the extracted insulin content of culture specimens. The ICCs in the matrix were refed with RPMI 1640, containing 10 mM nicotinamide, 10% fetal bovine serum (FBS), 11 mM D-glucose and with or without 0.1 mM 3-isobutyl-1-methylxanthine (IBMX) or 1.0 micrograms/ml caerulein. A comparison between the different culture media showed that embedded ICCs, maintained in RPMI 1640 with caerulein, in the presence of nicotinamide, had higher insulin content accumulation than when maintained in medium containing nicotinamide alone, but had impaired glucose-stimulated insulin secretion. In the medium containing IBMX and nicotinamide, embedded ICCs showed higher insulin accumulation but lower insulin content, compared to ICCs maintained in the presence of caerulein, and also showed impaired glucose-stimulated insulin release. Thus, the effect of nicotinamide on the survival and function of B-cells is amplified by the presence of caerulein or IBMX.

  1. Pulmonary physiology: future directions for lung function testing in COPD.

    PubMed

    Brusasco, Vito; Barisione, Giovanni; Crimi, Emanuele

    2015-02-01

    Chronic obstructive pulmonary disease (COPD) is a term that encompasses different pathological conditions having excessive airflow limitation in common. A wide body of knowledge has been accumulated over the last century explaining the mechanisms by which airway (chronic bronchitis) and parenchymal (emphysema) diseases lead to an indistinguishable spirometric abnormality. Although the definition of emphysema is anatomical, early studies showed that its presence can be inferred with good approximation from measurements of lung mechanics and gas exchange, in addition to simple spirometry. Studies using tests of ventilation distribution showed that abnormalities are present in smokers with normal spirometry, although these tests were not predictive of development of COPD. At the beginning of the third millennium, new documents and guidelines for diagnosis and treatment of COPD were developed, in which the functional diagnosis of COPD was restricted, for the sake of simplicity, to simple spirometry. In recent years, there has been a resurgence of interest in separating bronchitic from emphysematous phenotype of COPD. For this purpose, high-resolution computed tomography scanning has been added to diagnostic work-up. At the same time, methods for lung function testing have been refined and seem promising for detection of early small airways abnormalities. Among them are the forced oscillation technique and the nitrogen phase III slope analysis of the multiple-breath washout test, which may provide information on ventilation inhomogeneity. Moreover, the combined assessment of diffusing capacity for nitric oxide and carbon monoxide may be more sensitive than the latter alone for partitioning diffusive components at parenchymal level.

  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. 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.

  4. Pancreatic endocrine neoplasms: Epidemiology and prognosis of pancreatic endocrine tumors

    PubMed Central

    Halfdanarson, Thorvardur R.; Rubin, Joseph; Farnell, Michael B.; Grant, Clive S.; Petersen, Gloria M.

    2009-01-01

    Pancreatic endocrine neoplasms (PETs) are uncommon tumors with an annual incidence less than 1 per 100,000 persons per year in the general population. PETs that produce hormones resulting in symptoms are designated as functional. The majority of PETs are nonfunctional. Of the functional tumors, insulinomas are the most common, followed by gastrinomas. The clinical course of patients with PETs is variable and depends on the extent of the disease and the treatment rendered. Patients with completely resected tumors generally have a good prognosis, and aggressive surgical therapy in patients with advanced disease may also prolong survival. The epidemiology, prognosis and established and novel prognostic markers of PETs are reviewed. PMID:18508996

  5. Platelet function tests in clinical cardiology: unfulfilled expectations.

    PubMed

    Gorog, Diana A; Fuster, Valentin

    2013-05-28

    This review is a critical evaluation of publications in the past decade on the usefulness of platelet function tests (PFTs) in clinical cardiology, in aiding diagnosis, predicting risk, and monitoring therapy. The ideal PFT should: 1) detect baseline platelet hyperreactivity; 2) allow individualization of antiplatelet medication; 3) predict thrombotic risk; and 4) predict bleeding risk. The practicalities of clinical cardiology demand rapid, accurate, and reliable tests that are simple to operate at the bedside and available 24 h a day, 7 days a week. Point-of-care PFTs most widely evaluated clinically include PFA-100 and VerifyNow. None of these tests can reliably detect platelet hyperreactivity and thus identify a prothrombotic state. Identification of antiplatelet nonresponsiveness or hyporesponsiveness is highly test specific, and does not allow individualization of therapy. The power of PFTs in predicting thrombotic events for a given individual is variable and often modest, and alteration of antithrombotic treatment on the basis of the results of PFTs has not been shown to alter clinical outcome. PFTs in current mainstream use cannot reliably assess bleeding risk. These tests have been in use for over a decade, but the hopes raised by PFTs in clinical practice remain unfulfilled. Although physiologically relevant measurement of platelet function now is more important than ever, a critical reappraisal of available techniques in light of clinical requirements is needed. The use of native blood, global stimulus instead of individual agonists, contribution of thrombin generation by activated platelets to the test results, and establishment of a PFT therapeutic range for each antiplatelet drug should be considered and is discussed.

  6. 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

  7. Atherosclerosis and Liver Function Tests in Coronary Angiography Patients

    PubMed Central

    Doganer, YC; Rohrer, JE; Aydogan, U; Agerter, DC; Cayci, T; Barcin, C

    2015-01-01

    ABSTRACT Objective: Elevated aminotransferase levels indicating liver function, even in the normal range, have attracted great concern as potential novel markers of cardiovascular risk assessment. We hypothesized the possibility that liver function test variations in the normal range might be meaningfully associated to coronary artery disease (CAD). Method: Eighty-eight patients were randomly selected from those who underwent coronary angiography from June 2010 to June 2011 after applying to the outpatient cardiology clinic in Gulhane Military Medical Academy. According to the results of angiographies, patients were classified into three groups as normal, non-critical (< 50% involvement in coronaries), and critical (≥ 50% involvement in coronaries). In addition to angiographic intervention, measurements of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, albumin and the other serum parameters were performed in all patients. Results: The patient groups of CAD were balanced (28 critical cases, 30 non-critical cases and 30 normal cases). Mean age was 51.93 ± 9.3 (range 32–65) years and 19.3 per cent (n = 17) were females. Multiple linear regression analysis of all three liver function tests explained a significant portion of the variance, but adjusted r-squares were small (AST = 0.174, ALT = 0.242, albumin = 0.124). Albumin was significantly higher for patients with critical CAD than for patients with no CAD (beta = 3.205, p = 0.002). Non-critical CAD was not significantly different from no CAD for any of the dependent variables. Mean AST was significantly higher for patients taking aspirin (beta = 0.218, p = 0.049), as was mean ALT (beta = 0.264, p = 0.015). Conclusion: Alanine aminotransferase and AST may not be associated with angiographically determined coronary atherosclerosis. Albumin may be more sensitive to demonstrate the burden of atherosclerosis. These results indicate that the association between the liver

  8. Effects of Differential Item Functioning on Examinees' Test Performance and Reliability of Test

    ERIC Educational Resources Information Center

    Lee, Yi-Hsuan; Zhang, Jinming

    2017-01-01

    Simulations were conducted to examine the effect of differential item functioning (DIF) on measurement consequences such as total scores, item response theory (IRT) ability estimates, and test reliability in terms of the ratio of true-score variance to observed-score variance and the standard error of estimation for the IRT ability parameter. The…

  9. Hippo transducer TAZ promotes epithelial mesenchymal transition and supports pancreatic cancer progression

    PubMed Central

    Xie, Dacheng; Cui, Jiujie; Xia, Tian; Jia, Zhiliang; Wang, Liang; Wei, Wenfei; Zhu, Anna; Gao, Yong; Xie, Keping; Quan, Ming

    2015-01-01

    Transcriptional co-activator with PDZ binding motif (TAZ) is a transducer of the Hippo pathway and promotes cancer development and progression. In the present study, we sought to determine the roles and underlying mechanisms of elevated expression and activation of TAZ in pancreatic cancer development and progression. The mechanistic role of TAZ and Hippo signaling in promotion of pancreatic cancer development and progression was examined using cell culture, molecular biology, and mouse models. The relevance of our experimental and mechanistic findings was validated using human pancreatic tumor specimens. We found that TAZ expression was markedly higher in pancreatic tumors than in normal pancreatic tissue. Further analysis of the correlation of TAZ expression with tissue microarray clinicopathologic parameters revealed that this expression was positively associated with tumor differentiation. Also, TAZ expression was higher in pancreatic cancer cell lines than in pancreatic ductal epithelial cells. TAZ activation in pancreatic cancer cells promoted their proliferation, migration, invasion, and epithelial-mesenchymal transition. Further mechanistic studies demonstrated that aberrant expression and activation of TAZ in pancreatic cancer cells resulted from suppression of the expression of Merlin, a positive regulator upstream of the Hippo pathway, and that the oncogenic function of TAZ in pancreatic cancer cells was mediated by TEA/ATTS domain transcription factors. Therefore, TAZ functioned as an oncogene and promoted pancreatic cancer epithelial-mesenchymal transition and progression. TAZ thus may be a target for effective therapeutic strategies for pancreatic cancer. PMID:26416426

  10. 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.

  11. Conduct disorder and cognitive functioning: testing three causal hypotheses.

    PubMed

    Schonfeld, I S; Shaffer, D; O'Connor, P; Portnoy, S

    1988-08-01

    The sample consisted of black adolescents who were members of the Columbia-Presbyterian chapter of the Collaborative Perinatal Project from birth to age 7. At age 17, subjects and their parents were administered a battery of instruments that included standardized psychiatric diagnostic interviews as part of a call-back study. Results from least-squares and logistic regression analyses were compatible with the hypothesis that deficiencies in cognitive functioning are causally related to adolescent conduct disorder as defined by DSM III. The results suggested that the relation of cognitive functioning to psychiatric status appears to be specific to conduct disorders. The results were incompatible with a "third" variable hypothesis (third factors included neurological status and environmental disadvantage) and the hypothesis that conduct problems lead to deficits in cognitive functioning. The 3 most (and equally) important factors in accounting for age-17 conduct disorder were cognitive functioning, parent psychopathology, and early aggression. A closer look at the data tentatively suggested that a broad deficiency in acculturational learning, rather than narrowly focused social cognitive differences or native endowment, constitutes a key element in the link between cognitive functioning and conduct disorder. Test bias was ruled out as a possible explanation for the results.

  12. Comparative Transcriptomics of Malaria Mosquito Testes: Function, Evolution, and Linkage

    PubMed Central

    Cassone, Bryan J.; Kay, Raissa G. G.; Daugherty, Matthew P.; White, Bradley J.

    2017-01-01

    Testes-biased genes evolve rapidly and are important in the establishment, solidification, and maintenance of reproductive isolation between incipient species. The Anopheles gambiae complex, a group of at least eight isomorphic mosquito species endemic to Sub-Saharan Africa, is an excellent system to explore the evolution of testes-biased genes. Within this group, the testes are an important tissue in the diversification process because hybridization between species results in sterile hybrid males, but fully fertile females. We conducted RNA sequencing of A. gambiae and A. merus carcass and testes to explore tissue- and species-specific patterns of gene expression. Our data provides support for transcriptional repression of X-linked genes in the male germline, which likely drives demasculinization of the X chromosome. Testes-biased genes predominately function in cellular differentiation and show a number of interesting patterns indicative of their rapid evolution, including elevated dN/dS values, low evolutionary conservation, poor annotation in existing reference genomes, and a high likelihood of differential expression between species. PMID:28159865

  13. 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.

  14. Glucagon-like Peptide-1 Protects Pancreatic Beta-cells from Death by Increasing Autophagic Flux and Restoring Lysosomal Function.

    PubMed

    Zummo, Francesco P; Cullen, Kirsty S; Honkanen-Scott, Minna; Shaw, James Am; Lovat, Penny E; Arden, Catherine

    2017-02-23

    Studies in animal models of type 2 diabetes have shown that glucagon-like peptide-1 (GLP-1) receptor agonists prevent β-cell loss. Whether GLP-1 mediates β-cell survival via the key lysosomal-mediated process of autophagy is unknown.Here we report that treatment of INS-1E β-cells and primary islets with glucolipotoxicity (0.5mmol/l palmitate, 25mmol/l glucose) increases LC3 II, a marker of autophagy. Further analysis indicates a blockage in autophagic flux associated with lysosomal dysfunction. Accumulation of defective lysosomes leads to lysosomal membrane permeabilisation (LMP) and release of Cathepsin D, which contributes to cell death. Our data further demonstrated defects in autophagic flux and lysosomal staining in human samples of type 2 diabetes. Co-treatment with the GLP-1 receptor agonist exendin-4 reversed the lysosomal dysfunction, relieving the impairment in autophagic flux and further stimulated autophagy. siRNA knockdown showed the restoration of autophagic flux is also essential for the protective effects of exendin-4.Collectively, our data highlights lysosomal dysfunction as a critical mediator of β-cell loss and shows that exendin-4 improves cell survival via restoration of lysosomal function and autophagic flux. Modulation of autophagy / lysosomal homeostasis may thus define a novel therapeutic strategy for type 2 diabetes, with the GLP-1 signalling pathway as a potential focus.

  15. Standards for thyroid laboratory testing, and cognitive functions after menopause

    PubMed Central

    Bejga, Przemysław; Witczak, Mariusz; Łyszcz, Robert; Makara-Studzinska, Marta

    2014-01-01

    Introduction The aim of the study is to analyze the relationship between normative and non-normative thyroid tests (TSH, TT4, TT3, FT3, FT4, anti-TPO, anti-Tg, AB-TSHR) and the level of cognitive functions in postmenopausal women. Material and methods The study group consisted of 383 women from south-eastern Poland, aged 50-65 years. The cognitive functions were evaluated using a diagnostic instrument – Central Nervous System – Vital Signs (CNS-VS). Blood was collected for determination of the following parameters: TSH, TT4, TT3, FT3, FT4, anti-TPO, anti-Tg, AB-TSHR. Results There were significant differences in NCI, executive functions, psychomotor speed, reaction time, complex attention and cognitive flexibility, depending on the normative and non-normative level of TSH. Women whose level of FT3 was at the lower limit of the normal range obtained poorer results in psychomotor speed, while subjects with levels of FT4 below the standard achieved significantly lower scores for this function. The relationship between NCI and cognitive functions, and the normative and non-normative anti-TPO results, showed significant differences in verbal memory, visual memory, processing speed and reaction time. The level of AB-TSHR reported as normal or above the norm significantly differentiated from the results of NCI, processing speed, executive functions, psychomotor speed, complex attention and cognitive flexibility. Conclusions Concentrations of laboratory parameters assessing the thyroid function located within the upper limits of the normal range showed a different relationship with the cognitive performance than concentrations located within the lower limits of the standard. PMID:26327860

  16. 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

  17. Prognostic markers in acute pancreatitis.

    PubMed

    Gomatos, Ilias P; Xiaodong, Xu; Ghaneh, Paula; Halloran, Christopher; Raraty, Michael; Lane, Brian; Sutton, Robert; Neoptolemos, John P

    2014-04-01

    Acute pancreatitis has a mortality rate of 5-10%. Early deaths are mainly due to multiorgan failure and late deaths are due to septic complications from pancreatic necrosis. The recently described 2012 Revised Atlanta Classification and the Determinant Classification both provide a more accurate description of edematous and necrotizing pancreatitis and local complications. The 2012 Revised Atlanta Classification uses the modified Marshall scoring system for assessing organ dysfunction. The Determinant Classification uses the sepsis-related organ failure assessment scoring system for organ dysfunction and, unlike the 2012 Revised Atlanta Classification, includes infected necrosis as a criterion of severity. These scoring systems are used to assess systemic complications requiring intensive therapy unit support and intra-abdominal complications requiring minimally invasive interventions. Numerous prognostic systems and markers have been evaluated but only the Glasgow system and serum CRP levels provide pragmatic prognostic accuracy early on. Novel concepts using genetic, transcriptomic and proteomic profiling and also functional imaging for the identification of specific disease patterns are now required.

  18. 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.

  19. [Pulmonary function testing in Japan: present status and new developments].

    PubMed

    Tojo, Naoko

    2012-09-01

    In 2004, the Japanese Respiratory Society issued an initial set of recommendations on the standardized measurement of the most frequently used tests for pulmonary function, i.e., tests to assess slow vital capacity, forced vital capacity, and single-breath carbon monoxide diffusing capacity. This statement has not been updated, and the prediction equations for pulmonary function testing are not fully established. Thus, the guidelines will need to be periodically updated in accordance with new developments in this rapidly evolving field. Nitric oxide (NO) is now recognized as a biological mediator in animals and humans. The human lung produces NO and exhales it in breath. The fractional nitric oxide (NO) concentration in exhaled breath (FE(NO)) can be quantitatively measured by a simple, safe, and noninvasive procedure as a complementary tool for assessing airway inflammation in airway diseases such as asthma. While the measurement of exhaled NO is standardized for clinical use, FE(NO) measurement is not approved or covered under the public health insurance system in Japan.

  20. The reliability of a functional agility test for water polo.

    PubMed

    Tucher, Guilherme; de Souza Castro, Flávio Antônio; Garrido, Nuno Domingos; Martins da Silva, António José Rocha

    2014-06-28

    Few functional agility tests for water polo take into consideration its specific characteristics. The preliminary objective of this study was to evaluate the reliability of an agility test for water polo players. Fifteen players (16.3 ± 1.8 years old) with a minimum of two years of competitive experience were evaluated. A Functional Test for Agility Performance (FTAP) was designed to represent the context of this sport. Several trials were performed to familiarize the athlete with the movement. Two experienced coaches measured three repetitions of the FTAP. Descriptive statistics, repeated measures analysis of variance (ANOVA), 95% limit of agreement (LOA), intraclass correlation coefficient (ICC) and standard error of measurements (SEM) were used for data analysis. It was considered that certain criteria of reliability measures were met. There was no significant difference between the repetitions, which may be explained by an effect of the evaluator, the ability of the players or fatigue (p > 0.05). The ICC average from evaluators was high (0.88). The SEM varied between 0.13 s and 0.49 s. The CV average considering each individual was near 6-7%. These values depended on the condition of measurement. As the FTAP contains some characteristics that create a degree of unpredictability, the same athlete may reach different performance results, increasing variability. An adjustment in the sample, familiarization and careful selection of subjects help to improve this situation and enhance the reliability of the indicators.

  1. 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.

  2. Study on Noncontact Pulmonary Function Test Using Pattern Light Projection

    NASA Astrophysics Data System (ADS)

    Aoki, Hirooki; Koshiji, Kohji

    The pulmonary function test by spirometer is generally conducted. The test subjects, especially children, women and older people, feel uncomfortable as the mouthpiece and nasal plug must be attached to the face of them. We have studied the nonrestraint pulmonary function test using the dot matrix pattern projection in order to decrease the burden to the examinee. In our proposed system, the pattern light projector illuminates the thorax with the dot matrix pattern light. And the CCD camera takes a series of images of the dot matrix pattern. The three dimensional shape of the thorax surface can be calculated by the distribution of light dots. And the respiratory waveform is calculated by the time-series change of the three dimensional shape. The respiratory waveform of our system was similar to one of spirometer. Therefore, we clarified that our proposed system can equivalently measure the respiration with spirometer. And we compared the volume change of the three dimensional shape calculated by our system with the expired tidal volume measured by the expiration gas analyzer. And we examined the relationship between the expired tidal volume and the volume change of the thorax surface.

  3. Impact of Global Fxr Deficiency on Experimental Acute Pancreatitis and Genetic Variation in the FXR Locus in Human Acute Pancreatitis

    PubMed Central

    Nijmeijer, Rian M.; Schaap, Frank G.; Smits, Alexander J. J.; Kremer, Andreas E.; Akkermans, Louis M. A.; Kroese, Alfons B. A.; Rijkers, Ger. T.; Schipper, Marguerite E. I.; Verheem, André; Wijmenga, Cisca; Gooszen, Hein G.; van Erpecum, Karel J.

    2014-01-01

    Background Infectious complications often occur in acute pancreatitis, related to impaired intestinal barrier function, with prolonged disease course and even mortality as a result. The bile salt nuclear receptor farnesoid X receptor (FXR), which is expressed in the ileum, liver and other organs including the pancreas, exhibits anti-inflammatory effects by inhibiting NF-κB activation and is implicated in maintaining intestinal barrier integrity and preventing bacterial overgrowth and translocation. Here we explore, with the aid of complementary animal and human experiments, the potential role of FXR in acute pancreatitis. Methods Experimental acute pancreatitis was induced using the CCK-analogue cerulein in wild-type and Fxr-/- mice. Severity of acute pancreatitis was assessed using histology and a semi-quantitative scoring system. Ileal permeability was analyzed in vitro by Ussing chambers and an in vivo permeability assay. Gene expression of Fxr and Fxr target genes was studied by quantitative RT-PCR. Serum FGF19 levels were determined by ELISA in acute pancreatitis patients and healthy volunteers. A genetic association study in 387 acute pancreatitis patients and 853 controls was performed using 9 tagging single nucleotide polymorphisms (SNPs) covering the complete FXR gene and two additional functional SNPs. Results In wild-type mice with acute pancreatitis, ileal transepithelial resistance was reduced and ileal mRNA expression of Fxr target genes Fgf15, SHP, and IBABP was decreased. Nevertheless, Fxr-/- mice did not exhibit a more severe acute pancreatitis than wild-type mice. In patients with acute pancreatitis, FGF19 levels were lower than in controls. However, there were no associations of FXR SNPs or haplotypes with susceptibility to acute pancreatitis, or its course, outcome or etiology. Conclusion We found no evidence for a major role of FXR in acute human or murine pancreatitis. The observed altered Fxr activity during the course of disease may be a

  4. Human pancreatic cancer fusion 2 (HPC2) 1-B3: a novel monoclonal antibody to screen for pancreatic ductal dysplasia.

    PubMed

    Morgan, Terry K; Hardiman, Karin; Corless, Christopher L; White, Sandra L; Bonnah, Robert; Van de Vrugt, Henry; Sheppard, Brett C; Grompe, Markus; Cosar, Ediz F; Streeter, Philip R

    2013-01-01

    BACKGROUND.: Pancreatic ductal adenocarcinoma is rarely detected early enough for patients to be cured. The objective of the authors was to develop a monoclonal antibody to distinguish adenocarcinoma and precancerous intraductal papillary mucinous neoplasia (IPMN) from benign epithelium. METHODS.: Mice were immunized with human pancreatic adenocarcinoma cells and monoclonal antibodies were screened against a panel of archived pancreatic tissue sections, including pancreatitis (23 cases), grade 1 IPMN (16 cases), grade 2 IPMN (9 cases), grade 3 IPMN (13 cases), and various grades of adenocarcinoma (17 cases). One monoclonal antibody, human pancreatic cancer fusion 2 (HPC2) 1-B3, which specifically immunostained adenocarcinoma and all grades of IPMN, was isolated. Subsequently, HPC2 1-B3 was evaluated in a retrospective series of 31 fine-needle aspiration (FNA) biopsies from clinically suspicious pancreatic lesions that had long-term clinical follow-up. RESULTS.: HPC2 1-B3 was negative in all 31 cases of chronic pancreatitis that were tested. In contrast, HPC2 1-B3 immunostained the cytoplasm and luminal surface of all 16 well- to moderately differentiated pancreatic ductal adenocarcinomas. It demonstrated only weak focal staining of poorly differentiated carcinomas. All high-grade IPMNs were found to be positive for HPC2 1-B3. The majority of low-grade to intermediate-grade IPMNs were positive (66% of cases). Immunostaining a separate series of pancreatic FNA cell blocks for HPC2 1-B3 demonstrated that the relative risk for detecting at least low-grade dysplasia (2.0 [95% confidence interval, 1.23-3.26]) was statistically significant (P = .002 by the Fisher exact test). CONCLUSIONS.: To reduce the mortality of pancreatic cancer, more effective early screening methods are necessary. The data from the current study indicate that a novel monoclonal antibody, HPC2 1-B3, may facilitate the diagnosis of early pancreatic dysplasia.

  5. Does an association exist between chronic pancreatitis and liver cirrhosis in alcoholic subjects?

    PubMed Central

    Aparisi, Luis; Sabater, Luis; Del-Olmo, Juan; Sastre, Juan; Serra, Miguel-Angel; Campello, Ricardo; Bautista, Daniel; Wassel, Abdalla; Rodrigo, José-Manuel

    2008-01-01

    AIM: To study the possible association between chronic pancreatitis (CP) and liver cirrhosis (LC) of alcoholic etiology, after excluding any other causes. METHODS: One hundred and forty consecutive alcoholic patients were subdivided into three groups: CP (n = 53), LC (n = 57), and asymptomatic alcoholic (n = 30). Clinical, biochemical and morphological characteristics, Child-Pugh index, indocyanine green test, and fecal pancreatic elastase-1 test were assessed. RESULTS: In patients with cirrhosis, major clinical manifestations of CP such as pancreatic pain and steatorrhea, as well as imaging alterations of CP such as calcifications, duct dilation and pseudocysts were absent; insulin-dependent diabetes was present in 5.3% of cases, and elastase-1 test was altered in only 7%, and severely altered in none. In patients with CP, clinical characteristics of cirrhosis such as ascites, encephalopathy and gastrointestinal hemorrhage were present in one case, Child-Pugh grade > A in 5.7%, and altered indocyanine green test in 1.9% cases. In asymptomatic alcoholism, there was only a non-coincident alteration of elastase-1 test and indocyanine test in 14.8% and 10%, respectively, but other characteristics of cirrhosis or CP were absent. An inverse correlation (r = -0.746) between elastase-1 test and indocyanine test was found in alcoholic patients. CONCLUSION: There is a scarce coincidence in clinical and morphological alterations among patients with CP or LC of alcoholic etiology, but an inverse correlation between pancreatic and liver function tests. These findings support that these alcoholic diseases evolve in a different manner and have different etiopathogenesis. PMID:18985807

  6. Epidemiology of pancreatic cancer

    PubMed Central

    Ilic, Milena; Ilic, Irena

    2016-01-01

    Cancer of the pancreas remains one of the deadliest cancer types. Based on the GLOBOCAN 2012 estimates, pancreatic cancer causes more than 331000 deaths per year, ranking as the seventh leading cause of cancer death in both sexes together. Globally, about 338000 people had pancreatic cancer in 2012, making it the 11th most common cancer. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends for pancreatic cancer incidence and mortality varied considerably in the world. A known cause of pancreatic cancer is tobacco smoking. This risk factor is likely to explain some of the international variations and gender differences. The overall five-year survival rate is about 6% (ranges from 2% to 9%), but this vary very small between developed and developing countries. To date, the causes of pancreatic cancer are still insufficiently known, although certain risk factors have been identified, such as smoking, obesity, genetics, diabetes, diet, inactivity. There are no current screening recommendations for pancreatic cancer, so primary prevention is of utmost importance. A better understanding of the etiology and identifying the risk factors is essential for the primary prevention of this disease. PMID:27956793

  7. Pancreatic groove cancer

    PubMed Central

    Ku, Yuan-Hao; Chen, Shih-Chin; Shyr, Bor-Uei; Lee, Rheun-Chuan; Shyr, Yi-Ming; Wang, Shin-E.

    2017-01-01

    Abstract Pancreatic groove cancer is very rare and can be indistinguishable from groove pancreatitis. This study is to clarify the characteristics, clinical features, managements, and survival outcomes of this rare tumor. Brief descriptions were made for each case of pancreatic groove cancer encountered at our institute. Individualized data of pancreatic groove cancer cases described in the literature were extracted and added to our database to expand the study sample size for a more complete analysis. A total of 33 patients with pancreatic groove cancer were included for analysis, including 4 cases from our institute. The median tumor size was 2.7 cm. The most common symptom was nausea or vomiting (89%), followed by jaundice (67%). Duodenal stenosis was noted by endoscopy in 96% of patients. The histopathological examination revealed well differentiated tumor in 43%. Perineural invasion was noted in 90%, and lymphovascular invasion and lymph node involvement in 83%. Overall 1-year survival rate was 93.3%, and 3- or 5-year survival rate was 62.2%, with a median survival of 11.0 months. Survival outcome for the well-differentiated tumors was better than those of the moderate/poorly differentiated ones. Early involvement of duodenum causing vomiting is often the initial presentation, but obstructive jaundice does not always happen until the disease progresses. Tumor differentiation is a prognostic factor for survival outcome. The possibility of pancreatic groove cancer should be carefully excluded before making the diagnosis of groove pancreatitis for any questionable case. PMID:28079795

  8. Pathophysiology of acute pancreatitis.

    PubMed

    Bhatia, Madhav; Wong, Fei Ling; Cao, Yang; Lau, Hon Yen; Huang, Jiali; Puneet, Padmam; Chevali, Lakshmi

    2005-01-01

    Acute pancreatitis is a common clinical condition. It is a disease of variable severity in which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The exact mechanisms by which diverse etiological factors induce an attack are still unclear. It is generally believed that the earliest events in acute pancreatitis occur within acinar cells. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction. If this inflammatory reaction is marked, it leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. Recent studies have established the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and the resultant MODS. At the same time, recent research has demonstrated the importance of acinar cell death in the form of apoptosis and necrosis as a determinant of pancreatitis severity. In this review, we will discuss about our current understanding of the pathophysiology of acute pancreatitis.

  9. Pancreatitis following liver transplantation.

    PubMed

    Alexander, J A; Demetrius, A J; Gavaler, J S; Makowka, L; Starzl, T E; Van Thiel, D H

    1988-06-01

    Since 1981, when the liver transplantation program was initiated at the University of Pittsburgh, we have been impressed with the prevalence of pancreatitis occurring following liver transplantation in patients transplanted for hepatitis B-related liver disease. To either confirm this clinical impression or refute it, the records of the 27 HbsAg+ patients and those of an additional 24 HbsAg- but HbcAb and/or HbsAb+ patients who underwent orthotopic liver transplantation were reviewed to determine the prevalence of clinical pancreatitis and hyperamylasemia (biochemical pancreatitis) following liver transplantation (OLTx). Post-OLTx hyperamylasemia occurred significantly more frequently in HbsAg+ patients (6/27) than it did in the HbsAg- patients (0/24) (P less than 0.05). More importantly, clinical pancreatitis occurred in 14% (4/27) of the HbsAg+ patients and 0% (0/24) of the HbsAg- patients. Interestingly, in each case, the pancreatitis was associated with the occurrence of acute hepatitis B infection of the allograft. Based upon these data, we conclude that pancreatitis occurring after liver transplantation is more common in patients transplanted for active viral liver disease caused by hepatitis B than in those with inactive viral liver disease. These observations suggest that pancreatitis occurring in, at least some cases following liver transplantation for viral liver disease, may result from hepatitis B virus infection of the pancreas.

  10. Diagnosis of autoimmune pancreatitis.

    PubMed

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

    2014-11-28

    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).

  11. 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

  12. Autonomic function testing aboard the ISS using “PNEUMOCARD”

    NASA Astrophysics Data System (ADS)

    Baevsky, R. M.; Funtova, I. I.; Diedrich, A.; Chernikova, A. G.; Drescher, J.; Baranov, V. M.; Tank, J.

    2009-10-01

    Investigations of blood pressure, heart rate (HR), and heart rate variability (HRV) during long term space flights on board the "ISS" have shown characteristic changes of autonomic cardiovascular control. Therefore, alterations of the autonomic nervous system occurring during spaceflight may be responsible for in- and post-flight disturbances. The device "Pneumocard" was developed to further investigate autonomic cardiovascular and respiratory function aboard the ISS. The hard-software diagnostic complex "Pneumocard" was used during in-flight experiment aboard ISS for autonomic function testing. ECG, photoplethysmography, respiration, transthoracic bioimpedance and seismocardiography were assessed in one male cosmonaut (flight lengths six month). Recordings were made prior to the flight, late during flight, and post-flight during spontaneous respiration and controlled respiration at different rates. HR remained stable during flight. The values were comparable to supine measurements on earth. Respiratory frequency and blood pressure decreased during flight. Post flight HR and BP values increased compared to in-flight data exceeding pre-flight values. Cardiac time intervals did not change dramatically during flight. Pulse wave transit time decreased during flight. The maximum of the first time derivative of the impedance cardiogram, which is highly correlated with stroke volume was not reduced in-flight. Our results demonstrate that autonomic function testing aboard the ISS using "Pneumocard" is feasible and generates data of good quality. Despite the decrease in BP, pulse wave transit time was found reduced in space as shown earlier. However, cardiac output did not decrease profoundly in the investigated cosmonaut. Autonomic testing during space flight detects individual changes in cardiovascular control and may add important information to standard medical control. The recent plans to support a flight to Mars, makes these kinds of observations all the more relevant

  13. 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.

  14. 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

  15. Limitation of liver function tests in metastatic carcinoid tumors

    SciTech Connect

    Moinuddin, M.; Dean, P.; Vander Zwaag, R.; Dragutsky, M.

    1987-04-01

    To evaluate the utility of liver function tests (LFT) as indicators of metastatic carcinoid tumors, a retrospective study was performed. The LFT results of 17 patients with carcinoid tumors metastatic to the liver were compared with 17 patients with other malignant tumors. In the noncarcinoid group, 82.4% of the patients had elevated alkaline phosphatase (AP) or gamma glutamyl transpeptidase (GGTP), whereas only 28.6% of carcinoid patients had abnormal enzymes. The medians of all LFT values were significantly higher in noncarcinoid patients than in the carcinoid group, except for glutamic pyruvic transaminase (SGPT). Our data indicate that LFT are helpful in screening for liver metastases in patients with noncarcinoid tumors, but are unreliable in carcinoid tumors. Imaging tests should be used to rule out liver metastases in carcinoid tumors, irrespective of LFT results.

  16. Testing Visual Functions in Patients with Visual Prostheses

    NASA Astrophysics Data System (ADS)

    Wilke, Robert; Bach, Michael; Wilhelm, Barbara; Durst, Wilhelm; Trauzettel-Klosinski, Susanne; Zrenner, Eberhart

    A number of different technical devices for restoring vision in blind patients have been proposed to date. They employ different strategies for the acquisition of optical information, image processing, and electrical stimulation. Devices with external cameras or with integrated components for light detection have been developed and are designed to stimulate such different sites as the retina, optic nerve, and cortex. First clinical trials for these devices are being planned or already underway. As vision with these artificial vision devices (AVDs) may differ considerably from natural vision and as it may not be possible to predict visual functions provided by such devices on the basis of technical specifications alone, novel test strategies are needed to comprehensively describe visual performance. We propose a battery of tests for standardized well-controlled investigations in these patients that allow for objective assessment of efficacy of these devices.

  17. Microcomputer based instrument for measuring a novel pulmonary function test

    NASA Astrophysics Data System (ADS)

    Craine, Brian L.; Craine, Eric R.

    1996-08-01

    The design of a prototype instrument for measuring the end-tidal concentration of carbon monoxide during human respiration is presented. The instrument automatically samples the final sixty cubic centimeters of exhaled breath, from successive breathing cycles, by coordinating a pump and the breathing cycle with a set of vacuum and pressure sensors. The concentration of carbon monoxide is measured using a nondispersive infrared spectrophotometer. The amount of carbon monoxide present is measured relative to the source air concentration eliminating the need for calibrating the instrument. The testing protocol and measurements can be controlled by a microcomputer connected to the instrument through a standard RS-232 serial interface. When at equilibrium, the end-tidal concentration of CO can be measured in a simple and reproducible fashion. This simplified technology allows for the construction of a small, portable, easy to use instrument that will allow the application of this new pulmonary function test at the point of contact with patients.

  18. 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

  19. From acute to chronic pancreatitis: the role of mutations in the pancreatic secretory trypsin inhibitor gene.

    PubMed

    Hirota, Masahiko; Kuwata, Kinuko; Ohmuraya, Masaki; Ogawa, Michio

    2003-03-01

    Pancreatic secretory trypsin inhibitor (PSTI) is a potent natural inhibitor of trypsin. We proposed the hypothesis that, if the function of the PSTI is impaired by its genetic mutation, trypsin may easily promote autodigestion causing pancreatitis and we performed a mutational analysis of the PSTI gene in patients with pancreatitis. Two exonic mutations (N34S and R67C) were thought to be associated with a predisposition to pancreatitis. The N34S mutation was co-segregated with two intronic mutations, IVS1-37T>C and IVS3-69insTTTT. Although we analyzed the function of the recombinant N34S protein, we could not demonstrate the loss of function of this protein. Intronic mutations, rather than N34S itself (IVS1-37T>C + N34S + IVS3-69insTTTT complex), may be associated with the decreased function of the PSTI. Alternatively, increased digestion of N34S in vivo may be applicable. As for R67C, the conformational alteration of the protein by forming intra-molecular or inter-molecular disulfide bonds with 67Cys was strongly suggested. These results, along with the brand-new findings in PSTI knockout mice, suggest that the genetic mutation of the PSTI is one of the important mechanisms for predisposition to pancreatitis by lowering the trypsin inhibitory function.

  20. Can Pancreatic Cancer Be Found Early?

    MedlinePlus

    ... Team About Pancreatic Cancer? Pancreatic Cancer Early Detection, Diagnosis, and Staging Can Pancreatic Cancer Be Found Early? Pancreatic cancer is hard to find early. The pancreas is deep inside the body, so early tumors ...

  1. Recurrent acute pancreatitis.

    PubMed

    Khurana, Vishal; Ganguly, Ishita

    2014-09-28

    Recurrent acute pancreatitis (RAP) is commonly encountered, but less commonly understood clinical entity, especially idiopathic RAP, with propensity to lead to repeated attacks and may be chronic pancreatitis if attacks continue to recur. A great number of studies have been published on acute pancreatitis, but few have focused on RAP. Analysing the results of clinical studies focusing specifically on RAP is problematic in view due to lack of standard definitions, randomised clinical trials, standard evaluation protocol used and less post intervention follow-up duration. With the availability of newer investigation modalities less number of etiologies will remains undiagnosed. This review particularly is focused on the present knowledge in understanding of RAP.

  2. [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.

  3. 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

  4. Highly adaptive tests for group differences in brain functional connectivity

    PubMed Central

    Kim, Junghi; Pan, Wei

    2015-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) and other technologies have been offering evidence and insights showing that altered brain functional networks are associated with neurological illnesses such as Alzheimer's disease. Exploring brain networks of clinical populations compared to those of controls would be a key inquiry to reveal underlying neurological processes related to such illnesses. For such a purpose, group-level inference is a necessary first step in order to establish whether there are any genuinely disrupted brain subnetworks. Such an analysis is also challenging due to the high dimensionality of the parameters in a network model and high noise levels in neuroimaging data. We are still in the early stage of method development as highlighted by Varoquaux and Craddock (2013) that “there is currently no unique solution, but a spectrum of related methods and analytical strategies” to learn and compare brain connectivity. In practice the important issue of how to choose several critical parameters in estimating a network, such as what association measure to use and what is the sparsity of the estimated network, has not been carefully addressed, largely because the answers are unknown yet. For example, even though the choice of tuning parameters in model estimation has been extensively discussed in the literature, as to be shown here, an optimal choice of a parameter for network estimation may not be optimal in the current context of hypothesis testing. Arbitrarily choosing or mis-specifying such parameters may lead to extremely low-powered tests. Here we develop highly adaptive tests to detect group differences in brain connectivity while accounting for unknown optimal choices of some tuning parameters. The proposed tests combine statistical evidence against a null hypothesis from multiple sources across a range of plausible tuning parameter values reflecting uncertainty with the unknown truth. These highly adaptive tests are not

  5. Inhibiting the Growth of Pancreatic Adenocarcinoma In Vitro and In Vivo through Targeted Treatment with Designer Gold Nanotherapeutics

    PubMed Central

    Kudgus, Rachel A.; Szabolcs, Annamaria; Khan, Jameel Ahmad; Walden, Chad A.; Reid, Joel M.; Robertson, J. David; Bhattacharya, Resham; Mukherjee, Priyabrata

    2013-01-01

    Background Pancreatic cancer is one of the deadliest of all human malignancies with limited options for therapy. Here, we report the development of an optimized targeted drug delivery system to inhibit advanced stage pancreatic tumor growth in an orthotopic mouse model. Method/Principal Findings Targeting specificity in vitro was confirmed by preincubation of the pancreatic cancer cells with C225 as well as Nitrobenzylthioinosine (NBMPR - nucleoside transporter (NT) inhibitor). Upon nanoconjugation functional activity of gemcitabine was retained as tested using a thymidine incorporation assay. Significant stability of the nanoconjugates was maintained, with only 12% release of gemcitabine over a 24-hour period in mouse plasma. Finally, an in vivo study demonstrated the inhibition of tumor growth through targeted delivery of a low dose of gemcitabine in an orthotopic model of pancreatic cancer, mimicking an advanced stage of the disease. Conclusion We demonstrated in this study that the gold nanoparticle-based therapeutic containing gemcitabine inhibited tumor growth in an advanced stage of the disease in an orthotopic model of pancreatic cancer. Future work would focus on understanding the pharmacokinetics and combining active targeting with passive targeting to further improve the therapeutic efficacy and increase survival. PMID:23483913

  6. Thyroid function testing in elephant seals in health and disease.

    PubMed

    Yochem, Pamela K; Gulland, Frances M D; Stewart, Brent S; Haulena, Martin; Mazet, Jonna A K; Boyce, Walter M

    2008-02-01

    Northern Elephant Seal Skin Disease (NESSD) is a severe, ulcerative, skin condition of unknown cause affecting primarily yearling northern elephant seals (Mirounga angustirostris); it has been associated with decreased levels of circulating thyroxine (T4) and triiodothyronine (T3). Abnormalities of the thyroid gland that result in decreased hormone levels (hypothyroidism) can result in hair loss, scaling and secondary skin infections. However, concurrent illness (including skin ailments) can suppress basal levels of thyroid hormones and mimic hypothyroidism; when this occurs in animals with normal thyroid glands it is called "sick euthyroid syndrome". The two conditions (true hypothyroidism vs. "sick euthyroid") can be distinguished in dogs by testing the response of the thyroid gland to exogenous thyrotropin (Thyroid Stimulating Hormone, TSH). To determine whether hypothyroidism is involved in the etiology of NESSD, we tested thyroid function of stranded yearling elephant seals in the following categories: healthy seals (rehabilitated and ready for release; N=9), seals suffering from NESSD (N=16) and seals with other illnesses (e.g., lungworm pneumonia; N=10). Levels of T4 increased significantly for all three categories of elephant seals following TSH stimulation, suggesting that seals with NESSD are "sick euthyroid" and that the disease is not associated with abnormal thyroid gland function.

  7. Contaminated aerosol recovery from pulmonary function testing equipment.

    PubMed

    Hiebert, T; Miles, J; Okeson, G C

    1999-02-01

    Clinically, the spread of infectious agents between subjects undergoing spirometry is quite uncommon. There is almost no documentation in the medical literature on this subject. We studied the retrieval of nonpathogenic Escherichia coli after aerosolizing organisms into standard pulmonary function tubing of a type that is frequently used by volume-sensing spirometers. The arrival of the aerosol at the distal end of the tubing was documented by culture. After delays of 0, 1, 5, and 10 min, respectively, air was forcibly withdrawn from the proximal end of the tubing through a special petri plate assembly. The plates were cultured and the colonies were counted. Immediately after insufflation of organisms, air withdrawn from the proximal tubing had counts similar to the air sampled at the distal end. After a 1-min delay, the proximal samples contained only rare organisms. No organisms were recovered from proximal air samples after a delay of 5 or 10 min after insufflation of organisms. The absence of detectable aerosolized E. coli after delays of 5 and 10 min after insufflation of organisms into spirometry tubing supports the hypothesis that a significant transfer of aerosolized organisms does not occur during routine pulmonary function testing as long as an interval of 5 min or more is allowed between tests.

  8. [Experimental models of acute pancreatitis].

    PubMed

    Ceranowicz, Piotr; Cieszkowski, Jakub; Warzecha, Zygmunt; Dembiński, Artur

    2015-02-21

    Acute pancreatitis is a severe disease with high mortality. Clinical studies can bring some data about etiology, pathogenesis and the course of acute pancreatitis. However, studies concerning early events of this disease and the new concepts of treatment cannot be performed on humans, due to ethical reasons. Animal models of acute pancreatitis have been developed to solve this problem. This review presents currently used experimental models of acute pancreatitis, their properties and clinical relevance. Experimental models of acute pancreatitis can be divided into in vivo (non-invasive and invasive) and ex vivo models. The onset, development, severity and extent of acute pancreatitis, as well as the mortality, vary considerably between these different models. Animal models reproducibly produce mild, moderate or severe acute pancreatitis. One of the most commonly used models of acute pancreatitis is created by administration of supramaximal doses of cerulein, an analog of cholecystokinin. This model produces acute mild edematous pancreatitis in rats, whereas administration of cerulein in mice leads to the development of acute necrotizing pancreatitis. Acute pancreatitis evoked by retrograde administration of sodium taurocholate into the pancreatic duct is the most often used model of acute severe necrotizing pancreatitis in rats. Ex vivo models allow to eliminate the influence of hormonal and nervous factors on the development of acute pancreatitis.

  9. [Strategies for screening for pancreatic adenocarcinoma in high-risk patients: the place of endoscopic ultrasound].

    PubMed

    Béchade, Dominique

    2011-03-01

    Screening high-risk individuals with imaging tests, such endoscopic ultrasound and computed tomography, can lead to the detection and treatment of predominantly asymptomatic premalignant lesions. These pancreatic lesions consist of resectable, mostly branch-type non invasive intraductal papillary mucinous neoplasms. Endoscopic ultrasound features of chronic pancreatitis are highly prevalent in high-risk individuals and these directly correlate with multifocal lobulocentric parenchymal atrophy due to pancreatic intraepithelial neoplasia. Long-term, multi-prospective studies are needed to determine if screening for early pancreatic adenocarcinoma and timely intervention results in decreased pancreatic cancer incidence and mortality in high-risk individuals.

  10. Potential role of NADPH oxidase in pathogenesis of pancreatitis.

    PubMed

    Cao, Wei-Li; Xiang, Xiao-Hui; Chen, Kai; Xu, Wei; Xia, Shi-Hai

    2014-08-15

    Studies have demonstrated that reactive oxygen species (ROS) are closely related to inflammatory disorders. Nicotinamide adenine dinucleotide phosphate oxidase (NOX), originally found in phagocytes, is the main source of ROS in nonphagocytic cells. Besides directly producing the detrimental highly reactive ROS to act on biomolecules (lipids, proteins, and nucleic acids), NOX can also activate multiple signal transduction pathways, which regulate cell growth, proliferation, differentiation and apoptosis by producing ROS. Recently, research on pancreatic NOX is no longer limited to inflammatory cells, but extends to the aspect of pancreatic acinar cells and pancreatic stellate cells, which are considered to be potentially associated with pancreatitis. In this review, we summarize the literature on NOX protein structure, activation, function and its role in the pathogenesis of pancreatitis.

  11. Potential role of NADPH oxidase in pathogenesis of pancreatitis

    PubMed Central

    Cao, Wei-Li; Xiang, Xiao-Hui; Chen, Kai; Xu, Wei; Xia, Shi-Hai

    2014-01-01

    Studies have demonstrated that reactive oxygen species (ROS) are closely related to inflammatory disorders. Nicotinamide adenine dinucleotide phosphate oxidase (NOX), originally found in phagocytes, is the main source of ROS in nonphagocytic cells. Besides directly producing the detrimental highly reactive ROS to act on biomolecules (lipids, proteins, and nucleic acids), NOX can also activate multiple signal transduction pathways, which regulate cell growth, proliferation, differentiation and apoptosis by producing ROS. Recently, research on pancreatic NOX is no longer limited to inflammatory cells, but extends to the aspect of pancreatic acinar cells and pancreatic stellate cells, which are considered to be potentially associated with pancreatitis. In this review, we summarize the literature on NOX protein structure, activation, function and its role in the pathogenesis of pancreatitis. PMID:25133019

  12. 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

  13. Visual function with acupuncture tested by visual evoked potential.

    PubMed

    Sagara, Yoshiko; Fuse, Nobuo; Seimiya, Motohiko; Yokokura, Syunji; Watanabe, Kei; Nakazawa, Toru; Kurusu, Masayuki; Seki, Takashi; Tamai, Makoto

    2006-07-01

    Visual evoked potential (VEP) testing is used frequently and is an important ophthalmologic physiological test to examine visual functions objectively. The VEP is a complicated waveform consisting of negative waveform named N75 and N135, and positive waveform named P100. Delayed P100 latency and greatly attenuated amplitude on VEP are known characteristics for diagnosing optic nerve disease. Acupuncture has been used to treat wide clinical symptoms with minimal side effects. The confirmation of the efficacy of acupuncture generally relies on subjective symptoms. There is not much scientific evidence supporting the acupuncture treatments for eye diseases up to today. However, the VEP test can evaluate objectively and numerically the efficacy of the treatment by the acupuncture. We analyzed 19 healthy subjects (38 eyes). The P100 latencies in the group of less than 101.7 msec (total average) before acupuncture stimulations were not different than those after treatment (98.2 +/- 3.0 msec, 98.2 +/- 4.0 msec, respectively, p = 0.88, n = 17), but the latencies in those subjects with longer or equal to 101.7 msec were statistically different after acupuncture (104.6 +/- 2.8 msec, 101.9 +/- 3.7 msec, respectively, p = 0.006, n = 21). These results show that the acupuncture stimulation contributes to the P100 latencies of pattern reversal (PR)-VEP to some subjects who have delayed latencies, and this electrophysiological method is a valuable technique in monitoring the effectiveness of acupuncture therapy in the improvements of visual functions. The purpose of this study is to evaluate the physiological effects by acupuncture stimulations using PR-VEP in normal subjects.

  14. Functional testing methods for the antiplatelet effects of aspirin.

    PubMed

    Schrör, Karsten; Huber, Kurt; Hohlfeld, Thomas

    2011-02-01

    At antiplatelet doses of 75-325 mg/day, aspirin irreversibly inhibits the platelet cyclooxygenase (COX)-1-dependent thromboxane A(2) (TXA(2)) formation. This is the pharmacological mode of action of aspirin, and it can be predicted that if aspirin does not inhibit COX-1 sufficiently, patients will not benefit from its antiplatelet effects. A pharmacodynamic failure of aspirin occurs in 1-2% of patients. The vast majority of atherothrombotic events in patients treated with aspirin result from mechanisms that are dependent on residual (non-COX-1-dependent) platelet reactivity. Global tests of platelet activation in vitro may identify patients with high residual platelet reactivity but are not sufficiently specific to test the pharmacological effect of aspirin. A further problem is the absence of standardized normal ranges for many assays and the fact that different equipment measures different signals, which are also influenced by the agonist and the anticoagulant used. Similar considerations apply for the determination of platelet-derived biomarkers such as circulating P-selectin, soluble CD40 ligand and others. The direct measurement of inhibition of thromboxane-forming capacity is the most specific pharmacological assay for aspirin. However, there is no linear correlation between inhibition of TXA(2) formation and inhibition of platelet function. Measurement of urinary levels of the TXB(2) metabolite, 11-dehydro-thromboxane B(2), represents an index of TXA(2) biosynthesis in vivo, but is also sensitive to other cellular sources of TXA(2). One general problem of all assays is the relationship with clinical outcome, which is still unclear. Monitoring aspirin treatment by testing platelet function or measuring biomarkers in clinical practice should not be recommended until a clear relationship for the predictive value of these assays for clinical outcome has been established.

  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. Functional toxicology: tools to advance the future of toxicity testing

    PubMed Central

    Gaytán, Brandon D.; Vulpe, Chris D.

    2014-01-01

    The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds—information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes. PMID:24847352

  18. Testing galaxy formation models with galaxy stellar mass functions

    NASA Astrophysics Data System (ADS)

    Lim, S. H.; Mo, H. J.; Lan, T.-W.; Ménard, B.

    2017-01-01

    We compare predictions of a number of empirical models and numerical simulations of galaxy formation to the conditional stellar mass functions 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 haloes changes behaviour 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 haloes, 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 haloes. 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.

  19. 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

  20. Pancreatic stellate cells: a starring role in normal and diseased pancreas

    PubMed Central

    Apte, Minoti V.; Pirola, Romano C.; Wilson, Jeremy S.

    2012-01-01

    While the morphology and function of cells of the exocrine and endocrine pancreas have been studied over several centuries, one important cell type in the gland, the pancreatic stellate cell (PSC), had remained undiscovered until as recently as 20 years ago. Even after its first description in 1982, it was to be another 16 years before its biology could begin to be studied, because it was only in 1998 that methods were developed to isolate and culture PSCs from rodent and human pancreas. PSCs are now known to play a critical role in pancreatic fibrosis, a consistent histological feature of two major diseases of the pancreas—chronic pancreatitis and pancreatic cancer. In health, PSCs maintain normal tissue architecture via regulation of the synthesis and degradation of extracellular matrix (ECM) proteins. Recent studies have also implied other functions for PSCs as progenitor cells, immune cells or intermediaries in exocrine pancreatic secretion in humans. During pancreatic injury, PSCs transform from their quiescent phase into an activated, myofibroblast-like phenotype that secretes excessive amounts of ECM proteins leading to the fibrosis of chronic pancreatitis and pancreatic cancer. An ever increasing number of factors that stimulate and/or inhibit PSC activation via paracrine and autocrine pathways are being identified and characterized. It is also now established that PSCs interact closely with pancreatic cancer cells to facilitate cancer progression. Based on these findings, several therapeutic strategies have been examined in experimental models of chronic pancreatitis as well as pancreatic cancer, in a bid to inhibit/retard PSC activation and thereby alleviate chronic pancreatitis or reduce tumor growth in pancreatic cancer. The challenge that remains is to translate these pre-clinical developments into clinically applicable treatments for patients with chronic pancreatitis and pancreatic cancer. PMID:22973234

  1. 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, ...

  2. 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, ...

  3. Chronic Pancreatitis in Children

    MedlinePlus

    ... years to appear, but this, too, is highly variable; some patients with chronic pancreatitis will develop diabetes ... of modifying factors include other genes or environmental variables, which is a term that scientists use to ...

  4. Pancreatic Cancer Risk Factors

    MedlinePlus

    ... age at the time of diagnosis is 71. Gender Men are slightly more likely to develop pancreatic ... would like to unsubscribe/opt out from our communications, please follow this link: http://www.cancer.org/ ...

  5. Fluid collections in and around the pancreas in acute pancreatitis.

    PubMed

    Brun, Alexander; Agarwal, Nanakram; Pitchumoni, C S

    2011-08-01

    The advent of computed tomographic scan with its wide use in the evaluation of acute pancreatitis has opened up a new topic in pancreatology i.e. fluid collections. Fluid collections in and around the pancreas occur often in acute pancreatitis and were defined by the Atlanta Symposium on Acute Pancreatitis in 1992. Two decades since the Atlanta Conference additional experience has brought to light the inadequacy and poor understanding of the terms used by different specialists involved in the care of patients with acute pancreatitis when interpreting imaging modalities and the need for a uniformly used classification system. The deficiencies of the Atlanta definitions and advances in medicine have led to a proposed revision of the Atlanta classification promulgated by the Acute Pancreatitis Classification Working Group. The newly used terms "acute peripancreatic fluid collections," "pancreatic pseudocyst," "postnecrotic pancreatic/peripancreatic fluid collections," and "walled-off pancreatic necrosis" are to be clearly understood in the interpretation of imaging studies. The current treatment methods for fluid collections are diverse and depend on accurate interpretations of radiologic tests. Management options include conservative treatment, percutaneous catheter drainage, open and laparoscopic surgery, and endoscopic drainage. The choice of treatment depends on a correct diagnosis of the type of fluid collection. In this study we have attempted to clarify the management and clinical features of different types of fluid collections as they have been initially defined under the 1992 Atlanta Classification and revised by the Working Group's proposed categorization.

  6. 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.

  7. [Management of postoperative pancreatic fistula].

    PubMed

    Hackert, T; Büchler, M W

    2015-06-01

    The occurrence of a postoperative pancreatic fistula is one of the most important complications following pancreatic resections. The frequency of this complication varies between 3 % after pancreatic head resection and up to 35 % following distal pancreatectomy. In 2005, the international definition of postoperative pancreatic fistula was standardized according to the approach of the International Study Group of Pancreatic Surgery (ISGPS) including an A-C grading system of the severity. Consequently, results from different studies have become comparable and the historically reported fistula rates can be evaluated more critically. The present review summarises the currently available data on incidence, risk factors, fistula-associated complications and management of postoperative pancreatic fistula.

  8. Arsenic-Induced Pancreatitis

    PubMed Central

    Connelly, Sean; Zancosky, Krysia; Farah, Katie

    2011-01-01

    The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide has brought about tremendous advancement in the treatment of acute promyelocytic myelogenous leukemia (APML). In most instances, the benefits of these treatments outweigh the risks associated with their respective safety profiles. Although acute pancreatitis is not commonly associated with arsenic toxicity, it should be considered as a possible side effect. We report a case of arsenic-induced pancreatitis in a patient with APML. PMID:22606427

  9. 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

  10. Pain on Functional Movement Screen Tests and Injury Risk.

    PubMed

    Bushman, Timothy T; Grier, Tyson L; Canham-Chervak, Michelle C; Anderson, Morgan K; North, William J; Jones, Bruce H

    2015-11-01

    The Functional Movement Screen (FMS) is a tool intended to evaluate limitations or asymmetries of movement to detect individuals at risk for exercise- and sports-related injury. The purpose was to determine the association and predictive value of specific FMS tests with injury risk in physically active men. Soldiers aged 18-57 years completed the FMS (n = 2,476). Demographic and fitness data were collected by survey. Medical record data for any, overuse, and traumatic injury 6 months after the assessment were obtained. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated along with receiver operator characteristics to determine area under the curve (AUC). Risks, risk ratios, odds ratios (ORs), and 95% confidence intervals were calculated to assess injury risks. Multivariate logistic regression identified that pain on 5 of the 7 tests was associated with greater risk for any injury (OR = 1.50-3.51): deep squat, hurdle step, in-line lunge, trunk stability push-up, and rotary stability. However, FMS registered low sensitivity, PPV, and AUC for all 7 tests for the 3 injury types (2-24% sensitivity, 16-74% PPV, and 50-58% AUC). Although the presence of pain was associated with a higher risk of injury on 5 tests, a low sensitivity, PPV, and AUC were displayed. Therefore, caution is advised when implementing the FMS as a screening tool in an Army or similarly active population as it could lead to prevention and treatment resources being directed toward individuals who are not at greater risk for injury.

  11. Tuboimpedance: A New Test of Eustachian Tube Function.

    PubMed

    Smith, Matthew E; Zou, Charlie C; Blythe, Andrew J C; Tysome, James R

    2017-04-01

    Objective Eustachian tube (ET) dysfunction is most frequently caused by a failure of the ET to adequately open; however, there is currently no reliable method of assessing this. Tubomanometry has recently shown good interindividual repeatability as a measure of ET function by measuring middle ear pressure after the application of regulated nasopharyngeal pressures during swallowing. We present the first reports of a novel test: middle ear impedance measurements during standard nasopharyngeal pressure application (tuboimpedance). We assess repeatability in healthy ears and any advantages over tubomanometry. Study Design Exploratory cohort diagnosis study. Setting Tertiary referral center. Subjects Twenty screened, healthy ears (10 volunteers). Methods Tubomanometry and tuboimpedance tests were performed while individuals swallowed with applied nasopharyngeal pressures of 20, 30, 40, and 50 mbar. Eustachian tube opening detection rate and test repeatability (measured by intraclass correlation coefficient [ICC]) for immediate and delayed repeats at each pressure were compared. Results ET opening was detected more frequently using tuboimpedance, with a 100% detection rate using a nasopharyngeal pressure of 30 mbar or more, compared to 88% to 96% with tubomanometry. Detection of ET opening at 20 mbar was possible with tuboimpedance. Repeatability of both tests was mostly strong (ICC >0.7) for both immediate and delayed repeats. Repeatability for the tubomanometry R value was only fair to moderate. Conclusion Tuboimpedance may provide a repeatable measure of ET opening that is easier to perform due to lower nasopharyngeal pressures required and fewer issues with poor ear-probe sealing. Further assessment in patients with different forms of ET dysfunction is required.

  12. Glycoproteins and glycoproteomics in pancreatic cancer

    PubMed Central

    Pan, Sheng; Brentnall, Teresa A; Chen, Ru

    2016-01-01

    Aberrations in protein glycosylation and polysaccharides play a pivotal role in pancreatic tumorigenesis, influencing cancer progression, metastasis, immuno-response and chemoresistance. Abnormal expression in sugar moieties can impact the function of various glycoproteins, including mucins, surface receptors, adhesive proteins, proteoglycans, as well as their effectors and binding ligands, resulting in an increase in pancreatic cancer invasiveness and a cancer-favored microenvironment. Recent advance in glycoproteomics, glycomics and other chemical biology techniques have been employed to better understand the complex mechanism of glycosylation events and how they orchestrate molecular activities in genomics, proteomics and metabolomics implicated in pancreatic adenocarcinoma. A variety of strategies have been demonstrated targeting protein glycosylation and polysaccharides for diagnostic and therapeutic development. PMID:27895417

  13. Exocrine pancreatic insufficiency in the cat.

    PubMed

    Steiner, Jörg M

    2012-08-01

    Exocrine pancreatic insufficiency (EPI) is a syndrome caused by an insufficient amount of pancreatic digestive enzymes in the small intestine. Clinical signs most commonly reported in cats with EPI are weight loss, loose and voluminous stools, steatorrhea, polyphagia, and in some cases a greasy soiling of the hair coat in the perianal region. Serum feline trypsin-like immunoreactivity concentration is the diagnostic test of choice for the diagnosis of affected cats. Treatment of cats with EPI consists of enzyme supplementation with either a powdered pancreatic extract or raw pancreas. Most cats with EPI also have severely decreased serum cobalamin concentrations and may require lifelong parenteral cobalamin supplementation. Most cats respond well to therapy and can have a normal life expectancy and quality of life.

  14. 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.

  15. 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.

  16. Functional Task Test: 1. Sensorimotor changes Associated with Postflight Alterations in Astronaut Functional Task Performance

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Arzeno, N. H.; Buxton, R. E.; Feiveson, A. H.; Kofman, I. S.; Lee, S. M. C.; Miller, C. A.; Mulavara, A. P.; Platts, S. H.; Peters, B. T.; Phillips, T.; Ploutz-Snyder, L. L.; Reschke, M. F.; Ryder, J. W.; Spiering, B. A.; Stenger, M. B.; Taylor, L. C.; Wickwire, P. J.; Wood, S. J.

    2011-01-01

    Space flight is known to cause alterations in multiple physiological systems including changes in sensorimotor, cardiovascular, and neuromuscular systems. These changes may affect a crewmember s ability to perform critical mission tasks immediately after landing on a planetary surface. The overall goal of this project is to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. This presentation will focus on the sensorimotor contributions to postflight functional performance.

  17. A NEW CLINICAL MUSCLE FUNCTION TEST FOR ASSESSMENT OF HIP EXTERNAL ROTATION STRENGTH: AUGUSTSSON STRENGTH TEST

    PubMed Central

    2016-