WorldWideScience

Sample records for pioglitazone preserves pancreatic

  1. Pioglitazone attenuates the severity of sodium taurocholate-induced severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Ping Xu; Xiao-Jiang Zhou; Ling-Quan Chen; Jiang Chen; Yong Xie; Long-Hua Lv; Xiao-Hua Hou

    2007-01-01

    AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ (PPARγ)ligand, on development of severe acute pancreatitis (SAP) and expression of nuclear factor-kappa B (NF-κB)and intercellular adhesion molecule-1 (ICAM-1) in the pancreas.METHODS: Male Sprague-Dawley (SD) rats (160-200 g)were randomly allocated into three groups (n = 18in each group): severe acute pancreatitis group,pioglitazone group, sham group. SAP was induced by retrograde infusion of 1 mL/kg body weight 5% sodium taurocholate (STC) into the biliopancreatic duct of male SD rats. Pioglitazone was injected intraperitoneally two hours piror to STC infusion. Blood and ascites were obtained for detecting amylase and ascitic capacity. Pancreatic wet/dry weight ratio, expression of NF-κB and ICAM-1 in pancreatic tissues were detected by immunohistochemical staining. Pancreatic tissue samples were stained with hematoxylin and eosin (HE)for routine optic microscopy.RESULTS: Sham group displayed normal pancreatic structure. SAP group showed diffuse hemorrhage,necrosis and severe edema in focal areas of pancreas.There was obvious adipo-saponification in abdominal cavity. Characteristics such as pancreatic hemorrhage,necrosis, severe edema and adipo-saponification were found in pioglitazone group, but the levels of those injuries were lower in pioglitazone group than those in SAP group. The wet/dry pancreatic weight ratio,ascetic capacity, serum and ascitic activities of anylase in the SAP group were significantly higher than those in the sham group and pioglitazone group respectively (6969.50 ± 1368.99 vs 2104.67 ± 377.16, 3.99 ± 1.22 vs 2.48 ± 0.74, P < 0.01 or P < 0.05). According to Kusske criteria, the pancreatic histologic score showed that interstitial edema, inflammatory infiltration,parenchyma necrosis and parenchyma hommorrhage in SAP group significantly differed from those in the sham group and pioglitazone group (7.17 ± 1.83 vs 0.50 ±0.55, 7

  2. Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Peter C Konturek; Artur Dembinski; Zygmunt Warzecha; Grzegorz Burnat; Piotr Ceranowicz; Eckhart G Hahn; Marcin Dembinski; Romana Tomaszewska; Stanislaw J Konturek

    2005-01-01

    AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ (PPARγ)ligand, on the development of acute pancreatitis (AP) and on the expression of heat shock protein 70 (HSP70) in the pancreas.METHODS: AP was induced in rats by subcutaneous infusion of cerulein for 5 h. Pancreatic blood flow was measured by laser Doppler flowmetry. Plasma lipase activity, interleukin-1β (IL-1β) and IL-10 were determined.Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1β and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein.RESULTS: Pioglitazone administered (10-100 mg/kg I.g.)30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis (CIP) as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity,plasma concentration of pro-inflammatory IL-1β and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment.CONCLUSION: Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-inflammatory activities, to the suppression of IL-1β and to the overexpression of HSP70.PPARγ ligands could represent a new therapeutic option in the treatment of AP.

  3. Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis

    Science.gov (United States)

    Konturek, Peter C; Dembinski, Artur; Warzecha, Zygmunt; Burnat, Grzegorz; Ceranowicz, Piotr; Hahn, Eckhart G; Dembinski, Marcin; Tomaszewska, Romana; Konturek, Stanislaw J

    2005-01-01

    AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ (PPARγ) ligand, on the development of acute pancreatitis (AP) and on the expression of heat shock protein 70 (HSP70) in the pancreas. METHODS: AP was induced in rats by subcutaneous infusion of cerulein for 5 h. Pancreatic blood flow was measured by laser Doppler flowmetry. Plasma lipase activity, interleukin-1β (IL-1β) and IL-10 were determined. Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1β and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein. RESULTS: Pioglitazone administered (10-100 mg/kg i.g.) 30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis (CIP) as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity, plasma concentration of pro-inflammatory IL-1β and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment. CONCLUSION: Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-inflammatory activities, to the suppression of IL-1β and to the overexpression of HSP70. PPARγ ligands could represent a new therapeutic option in the treatment of AP. PMID:16419161

  4. Enhancing pancreatic Beta-cell regeneration in vivo with pioglitazone and alogliptin.

    Directory of Open Access Journals (Sweden)

    Hao Yin

    Full Text Available AIMS/HYPOTHESIS: Pancreatic beta-cells retain limited ability to regenerate and proliferate after various physiologic triggers. Identifying therapies that are able to enhance beta-cell regeneration may therefore be useful for the treatment of both type 1 and type 2 diabetes. METHODS: In this study we investigated endogenous and transplanted beta-cell regeneration by serially quantifying changes in bioluminescence from beta-cells from transgenic mice expressing firefly luciferase under the control of the mouse insulin I promoter. We tested the ability of pioglitazone and alogliptin, two drugs developed for the treatment of type 2 diabetes, to enhance beta-cell regeneration, and also defined the effect of the immunosuppression with rapamycin and tacrolimus on transplanted islet beta mass. RESULTS: Pioglitazone is a stimulator of nuclear receptor peroxisome proliferator-activated receptor gamma while alogliptin is a selective dipeptidyl peptidase IV inhibitor. Pioglitazone alone, or in combination with alogliptin, enhanced endogenous beta-cell regeneration in streptozotocin-treated mice, while alogliptin alone had modest effects. In a model of syngeneic islet transplantation, immunosuppression with rapamycin and tacrolimus induced an early loss of beta-cell mass, while treatment with insulin implants to maintain normoglycemia and pioglitazone plus alogliptin was able to partially promote beta-cell mass recovery. CONCLUSIONS/INTERPRETATION: These data highlight the utility of bioluminescence for serially quantifying functional beta-cell mass in living mice. They also demonstrate the ability of pioglitazone, used either alone or in combination with alogliptin, to enhance regeneration of endogenous islet beta-cells as well as transplanted islets into recipients treated with rapamycin and tacrolimus.

  5. Protective effects of fish oil and pioglitazone on pancreatic tissue in obese KK mice with type 2 diabetes.

    Science.gov (United States)

    Iizuka, Yuzuru; Kim, Hyounju; Izawa, Takuya; Sakurai, Koji; Hirako, Satoshi; Wada, Masahiro; Matsumoto, Akiyo

    2016-12-01

    n-3 Polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have protective effects against the pancreatic β-cell dysfunction through several mechanisms. Thiazolidines are insulin sensitizers and are used in treating patients with type 2 diabetes. Our previous study demonstrated that a combination of fish oil, which is rich with EPA and DHA, and pioglitazone exerts beneficial effects on obesity and diabetes through their actions on the liver and adipose tissue. However, it remains largely unknown whether such combination therapy affects the pancreas. To answer this question, KK mice, which serve as a model for obesity and type 2 diabetes, were treated for 8 weeks with fish oil and pioglitazone. The combined regimen suppressed pancreatic islet hypertrophy (mean islet area decreased by an average of 49% vs. control) compared with mice treated with fish oil or pioglitazone alone (decreased by an average of 21% and 32% vs. control, respectively). Compared with the controls, individual or combined treatment significantly increased the percentage of β-cell area in the pancreatic islets, significantly decreased endoplasmic reticulum stress, and reduced the percentage of apoptotic cell death in the pancreatic islets. These findings suggest that fish oil and/or pioglitazone prevents β-cell dysfunction by improving the insulin resistance and decreasing the ER stress.

  6. Small amounts of tissue preserve pancreatic function

    Science.gov (United States)

    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

  7. Pioglitazone-induced congestive heart failure and pulmonary edema in a patient with preserved ejection fraction.

    Science.gov (United States)

    Jearath, Vaneet; Vashisht, Rajan; Rustagi, Vipul; Raina, Sujeet; Sharma, Rajesh

    2016-01-01

    Pioglitazone-induced heart failure is known in patients with underlying heart disease, but is not well documented in patients with normal left ventricular function. Pioglitazone has been very popular as it is an insulin sensitizer and insulin resistance is prevalent among Indians. Fluid retention exacerbates pre-existing heart failure or precipitates heart failure in a patient with underlying left ventricular dysfunction. However, pathogenesis of heart failure in a patient with normal left ventricular function is not known. Probably it is due to dose-related effect on pulmonary endothelial permeability, rather than alterations in left ventricular mass or ejection fraction. We report a patient who developed congestive heart failure and pulmonary edema with normal left ventricular function within 1 year of starting pioglitazone therapy. We have to be careful in monitoring all possible side effects during followup when patients are on pioglitazone therapy.

  8. Pioglitazone-induced congestive heart failure and pulmonary edema in a patient with preserved ejection fraction

    Science.gov (United States)

    Jearath, Vaneet; Vashisht, Rajan; Rustagi, Vipul; Raina, Sujeet; Sharma, Rajesh

    2016-01-01

    Pioglitazone-induced heart failure is known in patients with underlying heart disease, but is not well documented in patients with normal left ventricular function. Pioglitazone has been very popular as it is an insulin sensitizer and insulin resistance is prevalent among Indians. Fluid retention exacerbates pre-existing heart failure or precipitates heart failure in a patient with underlying left ventricular dysfunction. However, pathogenesis of heart failure in a patient with normal left ventricular function is not known. Probably it is due to dose-related effect on pulmonary endothelial permeability, rather than alterations in left ventricular mass or ejection fraction. We report a patient who developed congestive heart failure and pulmonary edema with normal left ventricular function within 1 year of starting pioglitazone therapy. We have to be careful in monitoring all possible side effects during followup when patients are on pioglitazone therapy. PMID:27127397

  9. Pioglitazone-induced congestive heart failure and pulmonary edema in a patient with preserved ejection fraction

    Directory of Open Access Journals (Sweden)

    Vaneet Jearath

    2016-01-01

    Full Text Available Pioglitazone-induced heart failure is known in patients with underlying heart disease, but is not well documented in patients with normal left ventricular function. Pioglitazone has been very popular as it is an insulin sensitizer and insulin resistance is prevalent among Indians. Fluid retention exacerbates pre-existing heart failure or precipitates heart failure in a patient with underlying left ventricular dysfunction. However, pathogenesis of heart failure in a patient with normal left ventricular function is not known. Probably it is due to dose-related effect on pulmonary endothelial permeability, rather than alterations in left ventricular mass or ejection fraction. We report a patient who developed congestive heart failure and pulmonary edema with normal left ventricular function within 1 year of starting pioglitazone therapy. We have to be careful in monitoring all possible side effects during followup when patients are on pioglitazone therapy.

  10. The peroxisome proliferator-activated receptor γ agonist pioglitazone preserves bone microarchitecture in experimental arthritis by reducing the interleukin-17-dependent osteoclastogenic pathway.

    Science.gov (United States)

    Koufany, Meriem; Chappard, Daniel; Netter, Patrick; Bastien, Claire; Weryha, Georges; Jouzeau, Jean-Yves; Moulin, David

    2013-12-01

    To investigate the effect of pioglitazone on inflammation-induced bone loss and changes in bone microarchitecture in rats with adjuvant-induced arthritis (AIA), focusing on the contribution of interleukin-17 (IL-17) and the balance of RANKL and osteoprotegerin (OPG). Male Lewis rats sensitized with Freund's complete adjuvant were treated orally for 21 days with 30 mg/kg/day of pioglitazone or vehicle. Arthritis severity was evaluated by clinical and histologic examination. Bone mineral density (BMD) was assessed by dual x-ray absorptiometry. The therapeutic effect of pioglitazone on changes of the bone architecture was determined by micro-computed tomography (micro-CT). Levels of RANKL, OPG, and IL-17 were determined by serum immunoassay and by synovial tissue immunohistochemistry. Messenger RNA for IL-17 and retinoic acid receptor-related orphan nuclear receptor γt (RORγt) was evaluated by quantitative reverse transcription-polymerase chain reaction and IL-17 promoter activity by gene-reporter assay. Micro-CT analysis revealed that pioglitazone treatment reduced arthritis severity and bone erosion scores and increased BMD in comparison to vehicle treatment. Cortical bone thickness was preserved, although the major beneficial effect of pioglitazone was on indices of the trabeculae, especially trabecular separation. Pioglitazone reduced the ratio of RANKL to OPG, in both the serum and the inflamed synovium. Circulating levels of IL-17 were significantly reduced by pioglitazone treatment, as were the percentages of IL-17-positive cells, mainly polymorphonuclear cells, in the inflamed synovium. Induction of IL-17 was strictly dependent on the binding of RORγt to IL-17 promoter, and lentiviral overexpression of peroxisome proliferator-activated receptor γ (PPARγ) reduced the expression of RORγt. Pioglitazone decreased the level of inflammatory bone destruction and protected the bone microarchitecture in rats with AIA by controlling the circulating and local

  11. A Metabolic Inhibitory Cocktail for Grave Cancers: Metformin, Pioglitazone and Lithium Combination in Treatment of Pancreatic Cancer and Glioblastoma Multiforme.

    Science.gov (United States)

    Elmaci, İlhan; Altinoz, Meric A

    2016-10-01

    Pancreatic cancer (PC) and glioblastoma multiforme (GBM) are among the human cancers with worst prognosis which require an urgent need for efficient therapies. Here, we propose to apply to treat both malignancies with a triple combination of drugs, which are already in use for different indications. Recent studies demonstrated a considerable link between risk of PC and diabetes. In experimental models, anti-diabetogenic agents suppress growth of PC, including metformin (M), pioglitazone (P) and lithium (L). L is used in psychiatric practice, yet also bears anti-diabetic potential and selectively inhibits glycogen synthase kinase-3 beta (GSK-3β). M, a biguanide class anti-diabetic agent shows anticancer activity via activating AMP-activated protein kinase (AMPK). Glitazones bind to PPAR-γ and inhibit NF-κB, triggering cell proliferation, apoptosis resistance and synthesis of inflammatory cytokines in cancer cells. Inhibition of inflammatory cytokines could simultaneously decrease tumor growth and alleviate cancer cachexia, having a major role in PC mortality. Furthermore, mutual synergistic interactions exist between PPAR-γ and GSK-3β, between AMPK and GSK-3β and between AMPK and PPAR-γ. In GBM, M blocks angiogenesis and migration in experimental models. Very noteworthy, among GBM patients with type 2 diabetes, usage of M significantly correlates with better survival while reverse is true for sulfonylureas. In experimental models, P synergies with ligands of RAR, RXR and statins in reducing growth of GBM. Further, usage of P was found to be lesser in anaplastic astrocytoma and GBM patients, indicating a protective effect of P against high-grade gliomas. L is accumulated in GBM cells faster and higher than in neuroblastoma cells, and its levels further increase with chronic exposure. Recent studies revealed anti-invasive potential of L in GBM cell lines. Here, we propose that a triple-agent regime including drugs already in clinical usage may provide a

  12. Pioglitazone pretreatment for acute necrotizing pancreatitis in rats%吡格列酮预处理对急性坏死性胰腺炎大鼠模型的影响

    Institute of Scientific and Technical Information of China (English)

    李清华; 徐萍; 陈令全; 刘丕; 吕农华

    2008-01-01

    Objective To investigate the effect of pretreatment of pioglitazone on acute necrotizing pancreatitis (ANP) rats. Methods ANP was induced by retrograde injection of 5% sedinm deoxycholate into bilio-pancreatic ducts. The animals were randomly divided into ANP (n=18), sham operation (n=18) and pioglitazone pretreatment group (n=18). Pioglitazone was given 20 mg/kg in pioglitazone group before ANP was induced. The rats were sacrificed 3 h, 6 h, 12 h after ANP induction, respectively. Bblood samples were taken for serum amylase measurement. Tissue samples of pancreas were harvested for morphological observation under conventional light microscopy. Pathological change of pancreas was evaluated by Hughes and Kusske score system. Results The concentration of serum amylase and the pancreatic histological score in pioglitazone and ANP groups were significantly higher than those in sham operation group (P<0.001 ). The concentration of serum amylase, Hughes and Kusske score in pioglitazone group at 12 h after ANP induction were (2980± 1080) U/L,4.50±2.07 and 7.50±1.05, respectively, and were lower than (7598±1072) U/L, 7.17±1.47 and 11.33±1.75 of ANP group at 12 h (P<0.01). Conclusions Pioglitazone pretreatment could decrease the serum level of amylase and the pancreatic histological score. Pioglitazone may ameliorate the severity of ANP.%目的 探讨吡格列酮预处理对ANP大鼠的影响.方法 54只大鼠采用经胆胰管逆行注射5%牛磺胆酸钠制备ANP模型.大鼠按随机数字法分为ANP组、吡格列酮组和假手术组,各18只.吡格列酮组在制模前2 h腹腔注射0.2%吡格列酮20 mg/kg体重.分别在术后3 h、6 h、12 h处死动物,取血检测血淀粉酶,取胰腺组织观察胰腺大体及组织学变化,分别按Hushes和Kusske标准评分.结果 术后3 h、6 h、12 h,ANP组及吡格列酮组血淀粉酶、胰腺大体病理的Hughes评分和胰腺组织学Kusske评分比假手术组明显升高;吡格列酮组大鼠术后12

  13. Robot-assisted spleen preserving pancreatic surgery in MEN1 patients

    NARCIS (Netherlands)

    Nell, Sjoerd; Brunaud, Laurent; Ayav, Ahmet; Bonsing, Bert A.; Groot Koerkamp, Bas; Nieveen van Dijkum, Els J.; Kazemier, Geert; de Kleine, Ruben H J; Hagendoorn, Jeroen; Molenaar, I. Quintus; Valk, Gerlof D.; Borel Rinkes, Inne H M; Vriens, Menno R.

    2016-01-01

    Background: Multiple Endocrine Neoplasia type 1 (MEN1) patients often undergo multiple pancreatic operations at a young age. Objective: To describe robot-assisted and laparoscopic spleen-preserving pancreatic surgery in MEN1 patients, and to compare both techniques. Methods: Robot-assisted

  14. Robot-assisted spleen preserving pancreatic surgery in MEN1 patients

    NARCIS (Netherlands)

    Nell, Sjoerd; Brunaud, Laurent; Ayav, Ahmet; Bonsing, Bert A.; Koerkamp, Bas Groot; van Dijkum, Els J. Nieveen; Kazemier, Geert; de Kleine, Ruben H. J.; Hagendoorn, Jeroen; Molenaar, I. Quintus; Valk, Gerlof D.; Rinkes, Inne H. M. Borel; Vriens, Menno R.

    2016-01-01

    BackgroundMultiple Endocrine Neoplasia type 1 (MEN1) patients often undergo multiple pancreatic operations at a young age. ObjectiveTo describe robot-assisted and laparoscopic spleen-preserving pancreatic surgery in MEN1 patients, and to compare both techniques. MethodsRobot-assisted

  15. Clonal preservation of human pancreatic cell line derived from primary pancreatic adenocarcinoma.

    Science.gov (United States)

    Mohammad, R M; Li, Y; Mohamed, A N; Pettit, G R; Adsay, V; Vaitkevicius, V K; Al-Katib, A M; Sarkar, F H

    1999-11-01

    Adenocarcinoma of the pancreas generally remains an incurable disease by available treatment modalities, demanding the development of a suitable cell-culture/animal model and the discovery and evaluation of novel therapeutic agents. We report the clonal preservation of a human pancreatic cell line (KCI-MOH1) established from a 74-year-old African-American man diagnosed with pancreatic cancer. Initially the human primary tumor was grown as a xenograft in SCID mice and, subsequently, a cell line was established from tumors grown as a xenograft as reported in our earlier publication. The molecular characterization of the primary tumor, the tumors grown as xenograft, and the cell line all revealed similar genotypic properties. By using an automated DNA sequencer, a K-ras mutation (codon 12, GGT to CGT, Gly to Arg) was detected in the pancreatic tumor tissue taken from the patient, whereas no p53 mutation was detected. The same K-ras mutation and unaltered p53 was also found in the xenograft tumor and in the KCI-MOH1 cell line. Chromosome analysis of the cultured cells revealed: 42,XY,add(3)(p11.2),der(7)t(7;12) (p22;q12),-10,-12,add (14)(p11),-18,add (20)(q13),-22/84, idemx2, which is the same chromosome complement found in xenograft tumors. The KCI-MOH1 cell line grows well in tissue culture and forms tumors in the SCID mice when implanted subcutaneously, as well as in orthotopic sites. The KCI-MOH1 cell line-derived SCID mouse xenograft model was used for efficacy evaluation of bryostatin 1, auristatin-PE, spongistatin 1, and gemcitabine alone and in combination. Tumor growth inhibition (T/C expressed as percentage), tumor growth delay (T - C), and log 10 kill for these agents were 38%, 22 days, and 0.53; 15%, 30 days, and 0.80; 24%, 25 days, and 0.66; and 10%, 33 days, and 0.90, respectively. When given in combination, two of seven gemcitabine + auristatin-PE-treated animals were free of tumors for 150 days and were considered cured. Animals treated with a

  16. Morbid obesity and subsequent pancreatic cancer: pylorus-preserving pancreatoduodenectomy after laparoscopic sleeve gastrectomy.

    Science.gov (United States)

    Küper, Markus A; Königsrainer, Ingmar; Schmidt, Diethard; Kramer, K Michael; Granderath, Frank A; Schneider, Joachim; Löb, Stefan; Zieker, Derek; Hartmann, Jörg T; Zdichavsky, Marty; Königsrainer, Alfred; Brücher, Björn L D M

    2009-03-01

    Morbid obesity is a recognized risk factor for gastrointestinal cancer. Little is known about pancreatic cancer developing after gastric bypass surgery or about surgery for this type of tumor following bariatric surgery. This report describes a case of pancreatic head cancer identified 3 months after laparoscopic sleeve gastrectomy for morbid obesity. During routine follow-up, mild abdominal pain and elevated pancreatic enzymes prompted computed tomography, which revealed mild edematous pancreatitis. Hyperbilirubinemia developed, and magnetic resonance imaging showed a pancreatic head tumor. CA19-9 was elevated. After a pylorus-preserving pancreatic head resection, the postoperative course was uneventful. The patient received adjuvant chemotherapy. Unfortunately, at the time of writing (9 months postoperatively), a local recurrence and hepatic metastases were diagnosed. Patients treated with bariatric surgery who develop new symptoms or report constant mild symptoms should be evaluated using endoscopy and radiomorphological imaging. Interdisciplinary obesity treatment can then offer significant benefits for the patient, particularly in the case of pancreatic cancer, which is still difficult to diagnose. In addition, there is a need for epidemiological studies of patients who undergo bariatric surgery and subsequently develop cancer.

  17. Laparoscopic distal pancreatectomy with preservation of the spleen and splenic vessels for pancreatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Yan-Guo Zheng

    2009-06-01

    Full Text Available Background: A laparoscopic surgery can be beneficial in a spleen-preserving distal pancreatectomy. Aims: This report shows a 60-year-old woman who presented to her persistent upper abdominal and bilateral lumbodorsal distending pain for one year. A computed tomography scan demonstrated a 4cm×5cm×5cm solid space-occupying mass in the distal pancreas. The patient was referred to minimally invasive surgery service for resection of the pancreatic lesion. Methods: A laparoscopic spleen-preserving distal pancreatectomy was performed. Results: The mass was completely excised, the pathological examination revealed pancreatic adenocarcinoma with grade II. The postoperative advantages of this approach were the early return of bowel function, minimal complications, and early resumption of normal activities. Conclusions: This case illustrates that minimally invasive surgery in the performance of a spleen-and-splenic-vessel preserving distal pancreatectomy is a feasible procedure without compromising the splenic function.

  18. Spleen-Preserving Distal Pancreatectomy for Pancreatic Trauma: A Series of Six Cases

    Directory of Open Access Journals (Sweden)

    Thakur Deen Yadav

    2007-07-01

    Full Text Available Context Spleen-preserving distal pancreatectomy is a well-accepted procedure for benign tumors of the distal pancreas. Its safety and feasibility have been proven. However many doctors have not used this procedure due to the trauma involved. Objective We present our experience of six cases of distal pancreatic trauma where we managed to preserve the spleen during distal pancreatectomy in an emergency procedure. Design Prospective analysis of the data. Participants Patients with distal pancreatic trauma admitted to the Department of Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh between July 2001 and June 2005. Intervention A spleen-preserving distal pancreatectomy was performed by preserving the splenic vessels to maintain a reliable splenic blood flow. Patients who were unstable after adequate resuscitation were excluded. Main outcome measures The preoperative characteristics, intraoperative findings and postoperative complications with follow-up were studied. Results Six patients were found suitable for spleen-preserving distal pancreatectomy based on their general condition and a preoperative spleen CECT. Five patients had been injured in car accidents and one patient had sustained a stab injury. The average duration of the surgery was 4.75±0.25 hours. All patients had associated hollow viscus injury which was repaired along with the spleen-preserving distal pancreatectomy. The most common post-operative complication was fever with basal atelectasis. One patient died postoperatively from hemodynamic instability. The other five patients are doing well and have not developed pancreatic endocrine insufficiency. Conclusion Although technically demanding, a spleen-preserving distal pancreatectomy can be performed safely in an emergency, and it avoids splenectomy-related problems in the post-operative period.

  19. Pancreatitis

    Science.gov (United States)

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

  20. Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970359 CT diagnosis of pancreatic carcinoma andchronic pancreatitis. LUAN Baoqing(栾宝庆), et al,Dept Radiol, Beijing Friendship Hosp, Capital Med U-niv, Beijing, 100050. Chin J Radiol 1997; 31(2): 114-118. Objective: To improve the diagnostic accuracy ofpancreatic carcinoma and chronic pancreatitis. Materi-

  1. Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950347 Pancreatic endorcine response to parenteralnutrition in experimental acute pancreatitis.SUN Xi-aoguang(孙晓光),et al.Dept Nucl Med,ZhongshanHosp,Shanghai Med Univ,Shanghai.Shanghai Med J1995;18(2),74-70.In order to study the pancreatic endocrine responseto parenteral nutrition (PN) in acute pancreatitis,thedisease was induced in dogs by injecting 4% tauro-cholate sodium 0.5ml/kg plus trypsin 0.5mg/kg into the pancreatic duct.Intravenous infusion of PN wasinitiated one hour after the establishment of the dis-

  2. Pioglitazone increases the glycolytic efficiency of human Sertoli cells with possible implications for spermatogenesis.

    Science.gov (United States)

    Meneses, M J; Bernardino, R L; Sá, R; Silva, J; Barros, A; Sousa, M; Silva, B M; Oliveira, P F; Alves, M G

    2016-10-01

    Pioglitazone is a synthetic agonist for the nuclear receptor peroxisome proliferator-activated receptor γ used to treat type 2 diabetes mellitus. Recently we reported that antidiabetic drugs regulate the nutritional support of spermatogenesis by Sertoli cells. Herein, we investigate the effects of pioglitazone on human Sertoli cells metabolism. Human Sertoli cells were cultured in the presence of pioglitazone (1, 10, 100μM). Protein levels of phosphofructokinase 1, lactate dehydrogenase, hexokinase, glucose transporters (GLUT1, GLUT2, GLUT3), monocarboxylate transporter 4 and oxidative phosphorylation complexes were determined by Western blot. Lactate dehydrogenase and alanine aminotransferase activity were assessed and metabolite production and consumption determined by proton nuclear magnetic resonance. Mitochondrial membrane potential was also determined. Glucose consumption more than doubled in human Sertoli cells stimulated with pioglitazone 100μM. Mitochondrial complex II protein levels increased 50% with exposure to pioglitazone (100μM) in human Sertoli cells, though mitochondrial membrane potential was decreased by 32%. The pharmacological concentration of pioglitazone (10μM) almost doubled lactate production and established crucial correlations among key intervenient of glycolysis. Moreover, in the same concentration, alanine aminotransferase decreased more than 80%. Our results suggest that pioglitazone (10μM) increases the efficiency of the glycolytic flux and lactate production by human Sertoli cells, which is essential to sustain and preserve the spermatogenic event. Thus, pioglitazone may improve male fertility and thus, be considered a suitable antidiabetic drug for men in reproductive age.

  3. [A Case of Pancreatic Metastasis of Osteosarcoma Resected Using Laparoscopic Spleen Preserving Distal Pancreatectomy].

    Science.gov (United States)

    Toyama, Hirochika; Asari, Sadaki; Goto, Tadahiro; Terai, Sachio; Shirakawa, Sachiyo; Nanno, Yoshihide; Mizumoto, Takuya; Fukumoto, Takumi; Ajiki, Tetsuo; Kido, Masahiro; Tanaka, Motofumi; Matsumoto, Taku; Kinoshita, Hisoka; Kuramitsu, Kaori; Ku, Yonson

    2016-11-01

    A 44-year-old woman underwent surgical resection and received preoperative and postoperative chemotherapy for conventional osteosarcoma in the right fibular head. Three years later, follow-up PET-CT revealed accumulation ofFDG in the tail ofthe pancreas. Contrast-enhanced computed tomography showed a 13mm well-circumscribed hypovascular tumor. EUS showed a heterogeneous solid tumor, which was diagnosed as metastasis ofosteosarcoma to the pancreas. Laparoscopic spleen preserving distal pancreatectomy(LAP-SPDP)was performed. Pathologically, the tumor was diagnosed as metastasis ofconventional osteosarcoma to the pancreas. Cells from pancreas islet tissue were detected in the tumor, suggesting invasion ofthe tumor into the pancreatic body and surrounding adipose tissue. Although postoperative chemotherapy was administered, lung metastasis was detected 1.1 years after surgery. Laparoscopic partial resection of the lung metastasis was performed, and the patient is still alive. Metastasis ofosteosarcoma to the pancreas is rare, and there is no report oflaparoscopic approach as a treatment. Herein, we report a case with several references.

  4. A meta-analysis of the long-term effects of chronic pancreatitis surgical treatments: duodenum-preserving pancreatic head resection versus pancreatoduodenectomy

    Institute of Scientific and Technical Information of China (English)

    L(U) Wen-ping; SHI Qing; ZHANG Wen-zhi; CAI Shou-wang; JIANG Kai; DONG Jia-hong

    2013-01-01

    Background Surgery is regarded as the most effective treatment to relieve pain and reduce complications in chronic pancreatitis (CP).Two major strategies exist:duodenum-preserving pancreatic head resection (DPPHR) and pancreatoduodenectomy (PD).Many studies suggest that DPPHR offers advantages during surgery and in the short-term; however,the long-term effects have not been thoroughly investigated.We analyzed the long-term outcomes of DPPHR and PD,over follow-up times of at least 1 year,to determine the optimal surgical treatment for CP.Methods We systemically reviewed all CP surgical treatment reports,and only included randomized controlled trials (RCT) comparing DPPHR and PD,excluding unqualified studies using several pre-specified criteria.When multiple publications of a single trial were found,the most comprehensive current data were selected.Characteristics of the study populations and long-term postoperative outcome parameters were collected.The quality of the studies and data was analyzed using RevMan 4.2 software.Results Five trials were qualified for meta-analysis,with 261 participants in total (114 in the DPPHR group and 147 in the PD group).There were no significant differences in the age,gender,or indications for surgery of each group.At the mean of 5.7-year (1-14 years) follow-up examination,DPPHR and PD resulted in equally effective pain relief,exocrine and endocrine function,and similar mortality rates (P >0.05); however,DPPHR patients had improved global quality of life and weight gain,and reduced diarrhea and fatigue (P <0.05).Conclusion DPPHR and PD result in equal pain relief,mortality,and pancreatic function; however,DPPHR provides superior long-term outcomes.

  5. Pylorus-preserving versus pylorus-resecting pancreaticoduodenectomy for periampullary and pancreatic carcinoma: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Chong Yang

    Full Text Available BACKGROUND: The aim of this meta-analysis was to compare the long-term survival, mortality, morbidity and the operation-related events in patients with periampullary and pancreatic carcinoma undergoing pylorus-preserving pancreaticoduodenectomy (PPPD and pylorus-resecting pancreaticoduodenectomy (PRPD. METHOD: A systematic search of literature databases (Cochrane Library, PubMed, EMBASE and Web of Science was performed to identify studies. Outcome measures comparing PPPD versus PRPD for periampullary and pancreatic carcinoma were long-term survival, mortality, morbidity (overall morbidity, delayed gastric emptying [DGE], pancreatic fistula, wound infection, postoperative bleeding, biliary leakage, ascites and gastroenterostomy leakage and operation related events (hospital stays, operating time, intraoperative blood loss and red blood cell transfusions. RESULTS: Eight randomized controlled trials (RCTs including 622 patients were identified and included in the analysis. Among these patients, it revealed no difference in long-term survival between the PPPD and PRPD groups (HR = 0.23, p = 0.11. There was a lower rate of DGE (RR = 2.35, p = 0.04, 95% CI, 1.06-5.21 with PRPD. Mortality, overall morbidity, pancreatic fistula, wound infection, postoperative bleeding, biliary leakage, ascites and gastroenterostomy leakage were not significantly different between the groups. PPPDs were performed more quickly than PRPDs (WMD = 53.25 minutes, p = 0.01, 95% CI, 12.53-93.97; and there was less estimated intraoperative blood loss (WMD = 365.21 ml, p = 0.006, 95% CI, 102.71-627.71 and fewer red blood cell transfusions (WMD = 0.29 U, p = 0.003, 95% CI, 0.10-0.48 in patients undergoing PPPD. The hospital stays showed no significant difference. CONCLUSIONS: PPPD had advantages over PRPD in operating time, intraoperative blood loss and red blood cell transfusions, but had a significantly higher rate of DGE for periampullary

  6. Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008318 Proteomics of hyperlipidemia-associated pancreatitis using differential gel electrophoresis and tandem mass spectrometry: experiment with rats. ZHANG Wei(张伟), et al. Dept Gastroenterol, Shanghai 1st Hosp, Shanghai Jiaotong Univ, Shanghai 200080. Natl Med J China 2008;88(16):1132-1131.Objective To analyze the injury mechanismof hyperlipidemia-associated acute pancreatitis utilizing pro-teomics.Methods Ten SD rats were fed with high fat feed to establish hyperlipidemic models,and 10 SD rats were fed with normal feed to be used as control group.

  7. Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009216 Relation of inositol 1,4,5-trisphosphate with calcium metabolism in rats with severe acute pancreatitis.SHI Chengxian(石承先),et al.Dept Live Bili Pancre Surg,Guizhou Prov Hosp,Guiyang 550002.World Chin J Digestol,2009;17(6):598-601.

  8. Protective effects of pioglitazone and/or liraglutide on pancreatic β-cells in db/db mice: Comparison of their effects between in an early and advanced stage of diabetes.

    Science.gov (United States)

    Kimura, Tomohiko; Kaneto, Hideaki; Shimoda, Masashi; Hirukawa, Hidenori; Okauchi, Seizo; Kohara, Kenji; Hamamoto, Sumiko; Tawaramoto, Kazuhito; Hashiramoto, Mitsuru; Kaku, Kohei

    2015-01-15

    The aim was to compare the protective effects of pioglitazone (PIO) and/or liraglutide (LIRA) on β-cells with the progression of diabetes. Male db/db mice were treated with PIO and/or LIRA for 2 weeks in an early and advanced stage. In an early stage insulin biosynthesis and secretion were markedly increased by PIO and LIRA which was not observed in an advanced stage. In concomitant with such phenomena, expression levels of various β-cell-related factors were up-regulated by PIO and LIRA only in an early stage. Furthermore, β-cell mass was also increased by the treatment only in an early stage. Although there was no difference in apoptosis ratio between the two stages, β-cell proliferation was augmented by the treatment only in an early stage. In conclusion, protective effects of pioglitazone and/or liraglutide on β-cells were more powerful in an early stage of diabetes compared to an advanced stage.

  9. 吡格列酮和非诺贝特对高脂饮食大鼠胰岛细胞内信号分子的影响%Effects of fenofibrate and pioglitazone on expressions of intracellular signaling molecules in pancreatic islet of high-fat diet-fed rats

    Institute of Scientific and Technical Information of China (English)

    冯婷; 杨波; 田浩明

    2008-01-01

    Objective To observe the effects of fenofibrate and pioglitazone on the expressions of PPAR- α, PPAR-γ, and intracellular signaling molecules in pancreatic islets of obese rats induced by high-fat diets. Methods SD obese rat models were established with high-fat diet, and 40 male rats were assigned to 4 groups including high-fat diet (HF group), high-fat diet with fenofibrate (FF group), pioglitazone (FP group) treatment, and control rats with normal diet (NC group). After 8 weeks intervention, immunohistochemistry was performed to evaluate the expressions of various proteins in islets; At the same time, islets mass were scored in tissue slides. Results Islets mass enlarged in HF group. The compositions of islet cells were the same as the control. The expression of insulin was lower in HF group than the control, but after using pioglitazone, less islets mass and more insulin expression were found in FP group. Compared with the control group, expressions of PPAR-α, PPAR-γ protein were reduced in HF group, and the expression of PPAR-α protein increased in FF group, and the expression of PPAR-γ protein was increased in FP group. The levels of NF-кB, p38 mitogen-activated protein kinase (MAPK), ERK1 proteins increased significantly in HF group, the expressions of NF-кB, p38 MAPK decreased in FF and FP groups, and the level of ERK1 decreased only in FP group, the protein level of I-кB showed no difference among control, HF group, and FF groups. Conclusion Fenofibrate and pioglitazone may partially protect islet cells function and improve survival by correcting the disturbance of intracellular signaling molecules.%目的 观察吡格列酮和非诺贝特对高脂饮食大鼠胰岛内PPAR-α、-γ和细胞内信号分子的影响.方法 40只雄性SD大鼠随机分为4组:空白对照组(NC)、单纯高脂饮食组(HF)、高脂+非诺贝特组(FF)、高脂+吡格列酮组(FP).HE染色测定胰岛面积;免疫组织化学方法检测胰岛

  10. Coefficient of beta-cell failure in patients with type 2 diabetes treated with pioglitazone or acarbose.

    Science.gov (United States)

    Göke, B; Lübben, G; Bates, P C

    2004-02-01

    A new method of assessing the coefficient of failure of pancreatic beta-cells from any index of glycaemia has been proposed. This method of analysis has been used to assess data on HbA1c and fasting glucose concentrations from a randomised study comparing pioglitazone with acarbose. Patients were treated for 26 weeks with either pioglitazone 45 mg once daily or acarbose 300 mg/day as 3 equal doses. Plasma HbA1c concentration was measured every two months and fasting glucose was measured monthly. The coefficient of failure was determined for each patient from the slope of the least squares regression line over time. The coefficient of failure from HbA1c was - 2.65 +/- 2.13 %/year with pioglitazone and - 1.25 +/- 3.11 %/year with acarbose, indicating improved beta-cell function in each case. The coefficient of failure was improved to a significantly greater extent with pioglitazone ( P Coefficient of failure from fasting blood glucose also showed a greater improvement with pioglitazone (- 53.1 +/- 95.0 mg/dl/year) than with acarbose (- 29.9 +/- 142.5 mg/dl/year; p = 0.049). The coefficient of failure showed a significantly greater improvement of beta-cell function with pioglitazone than with acarbose during 26 weeks of treatment.

  11. Current clinical evidence on pioglitazone pharmacogenomics

    Directory of Open Access Journals (Sweden)

    Marina eKawaguchi-Suzuki

    2013-11-01

    Full Text Available Pioglitazone is the most widely used thiazolidinedione and acts as an insulin-sensitizer through activation of the Peroxisome Proliferator-Activated Receptor-γ (PPARγ. Pioglitazone is approved for use in the management of type 2 diabetes mellitus, but its use in other therapeutic areas is increasing due to pleiotropic effects. In this hypothesis article, the current clinical evidence on pioglitazone pharmacogenomics is summarized and related to variability in pioglitazone response. How genetic variation in the human genome affects the pharmacokinetics and pharmacodynamics of pioglitazone was examined. For pharmacodynamic effects, hypoglycemic and anti-atherosclerotic effects, risks of fracture or edema, and the increase in body mass index in response to pioglitazone based on genotype were examined. The genes CYP2C8 and PPARG are the most extensively studied to date and selected polymorphisms contribute to respective variability in pioglitazone pharmacokinetics and pharmacodynamics. We hypothesized that genetic variation in pioglitazone pathway genes contributes meaningfully to the clinically observed variability in drug response. To test the hypothesis that genetic variation in PPARG associates with variability in pioglitazone response, we conducted a meta-analysis to synthesize the currently available data on the PPARG p.Pro12Ala polymorphism. The results showed that PPARG 12Ala carriers had a more favorable change in fasting blood glucose from baseline as compared to patients with the wild-type Pro12Pro genotype (p=0.018. Unfortunately, findings for many other genes lack replication in independent cohorts to confirm association; further studies are needed. Also, the biological functionality of these polymorphisms is unknown. Based on current evidence, we propose that pharmacogenomics may provide an important tool to individualize pioglitazone therapy and better optimize therapy in patients with T2DM or other conditions for which pioglitazone

  12. Pioglitazone and cancer: angel or demon?

    Science.gov (United States)

    Kostapanos, Michael S; Elisaf, Moses S; Mikhailidis, Dimitri P

    2013-01-01

    After the withdrawal of troglitazone and rosiglitazone, pioglitazone remains the sole thiazolidinedione (TZD) still available. Pioglitazone is efficacious in improving glycemic control and reduce the risk of cardiovascular events. Although generally well-tolerated, pioglitazone was withdrawn by some national medicines agencies (e.g. in France and Germany) due to reports of increased incidence of bladder cancer. In this article, we review the literature on the association between pioglitazone and cancer in several sites, including the bladder. Pioglitazone, like other TZDs, increased differentiation, inhibited growth and proliferation, while provoked apoptosis in various cancer cells, including bladder cancer, in vitro and in vivo. However, a rat-specific carcinogenic effect of pioglitazone on the bladder was noted in vivo. Clinical data for the risk of various cancer sites mostly come from observational studies and are subject to bias. An increased risk for bladder cancer by pioglitazone was suggested by retrospective analyses. This risk was associated with the time of exposure and the age, by identifying 24 months and 65 years, respectively, as time 'thresholds' above which this risk becomes relevant. In contrast, no increased risk for bladder cancer was associated with pioglitazone in randomized clinical trials. Pioglitazone was associated with increased incidence of melanoma and non-Hodgkin lymphoma and decreased risk of renal cancer in one cohort study. These findings need to be re-evaluated on a prospective basis. There is no convincing evidence that pioglitazone increases or decreases the risk of cancer in other sites. In contrast, it was suggested that this drug may be useful either in the treatment of cancer complications or as an adjunct to chemotherapeutic agents. Considering the clinical benefit from the use of pioglitazone it is reasonable to wait until data from ongoing clinical trials are available before reaching definitive conclusions. Nevertheless

  13. Efficacy and tolerability of pioglitazone in patients with type 2 diabetes mellitus: comparison with other oral antihyperglycaemic agents.

    Science.gov (United States)

    Derosa, Giuseppe

    2010-10-22

    Diabetes mellitus is a debilitating disease that is estimated to affect 366 million people by the year 2030. Type 2 diabetes mellitus (T2DM) is characterized by a progressive decline in pancreatic β-cell function and increased insulin resistance, and accounts for approximately 90% of people with diabetes. Oral antihyperglycaemic agents are extensively used in the treatment of T2DM. Thiazolidinediones are insulin sensitizers developed specifically for T2DM, which act via activation of peroxisome proliferator-activated receptors (PPARs). Pioglitazone is a thiazolidinedione that displays high affinity for PPARγ(1) and PPARγ(2), which are predominately expressed in adipose tissue. This review examines the published literature comparing the efficacy and tolerability of pioglitazone with other oral antihyperglycaemic agents in the treatment of patients with T2DM. Glycosylated haemoglobin, fasting glucose, insulin parameters and β-cell function are all improved with pioglitazone treatment, with efficacy similar to third-generation sulfonylureas, metformin and dipeptidyl peptidase-4 inhibitors. Pioglitazone reduces vascular risk and inflammatory markers, and improves carotid intima media thickness independent of its glycaemic effect. When compared with rosiglitazone, pioglitazone is associated with a reduction in the risk of hospitalization for acute myocardial infarction. Blood pressure is reduced and lipid profiles are favourably improved with pioglitazone; however, an increased risk for the development/exacerbation of heart failure, which is related to the increased incidence of oedema due to fluid retention, and fractures remain a concern. A low incidence of hypoglycaemia is observed with pioglitazone, especially compared with sulfonylureas. In conclusion, pioglitazone is an effective oral antihyperglycaemic agent with additional cardiovascular and lipid benefits that allows for the successful management of patients with T2DM.

  14. COMPARISON OF METFORMIN AND PIOGLITAZONE IN PCOS

    Directory of Open Access Journals (Sweden)

    Archana V.

    2013-04-01

    Full Text Available ABSTRACT: OBJECTIVES: To compare and evaluate the effects of metformin and pioglitazone on insulin resistance, ovulation and hyperandrogenis m in women with PCOS. METHODS: Total 180 patients were included in this double blind cont rolled trial between 18 to 30 years. These women were randomly allocated in two groups. After t aking written consent they were treated with either metformin or pioglitazone for 6 months a nd pretreatment versus post treatment clinical and biochemical variables were analysed an d compared. RESULTS: After treatment with metformin and pioglitazone around 50- 55 % women in both group achieved menstrual cycle regularity , and ovulation was restored in 44 % and 55 % in patients on metformin and pioglitazone respectively. Both group showed decline i n F-G score. Decrease in serum cholesterol was seen in both groups , but was more pr onounced with pioglitazone. Effect on insulin resistance and hyperinsulinemia was assessed by measuring pre and post treatment fasting serum insulin levels . Fall in serum insuli n level was more with pioglitazone and 48 % women became normoinsulinemic after treatment with pioglitazone as compared to 12 % with metformin. Rise in serum SHBG and fall in LH level was more remarkable with pioglitazone (p value < 0.05.

  15. Preservation of beta cell function in adult human pancreatic islets for several months in vitro

    DEFF Research Database (Denmark)

    Brunstedt, J; Andersson, A; Frimodt-Møller, C

    1979-01-01

    Islets of Langerhans were isolated from four human kidney donors, aged 16 to 21 years by the collagenase method described for isolation of rodent islets. So far the human islets have been kept in tissue culture, without attachment, in medium RPMI 1640 supplemented with 10% calf serum for more than...... 9 months, with preservation of the ability to release insulin in response to glucose stimulation. Replacement of calf serum with serum from normal human subjects did not affect B-cell survival, but resulted in elevated insulin values partly due to lower insulin degrading activity. Thus the described...

  16. Importance of maintaining left gastric arterial flow at Appleby operation preserving whole stomach for central pancreatic cancer.

    Science.gov (United States)

    Kimura, Akifumi; Yamamoto, Junji; Aosasa, Suefumi; Hatsuse, Kazuo; Nishikawa, Makoto; Nishiyama, Kiyoshi; Tsujimoto, Hironori; Moriya, Tomoyuki; Hase, Kazuo; Shinmoto, Hiroshi; Kaji, Tatsumi

    2012-01-01

    The safety of whole stomach-preserving Appleby operation with resection of the left gastric artery (LGA) for pancreatic cancer cannot be assured. The anatomy of the celiac axis (CA) with special regard to the position of the origin of the LGA was examined. Using 3D images of the vascular architecture reconstructed from volume data of helical CT, the length of the CA and the position of the origin of the LGA from the CA were measured in 53 patients. Among 53 patients, 47 patients (89%) had classical anatomy of the CA branches. The mean length(2 standard deviation) of the CA and the distance from the root of the LGA to the bifurcation of the CA were 25.2mm (-4.9) (range 14.6-36.5) and 10.3mm (+4.5)(range 2.4-21.9), respectively. In 23 (45%) cases, the LGA arose farther than 10mm away from the bifurcation of the CA. Among six patients with anatomical variation of the arteries, two (4%) had the LGA directly arising from the aorta. Conservation of the LGA at modified Appleby operation would give complete cancer removal by en bloc resection of the nerve plexus, without risk of ischemic complications of the stomach and liver.

  17. Combination of Vildagliptin and Pioglitazone in Experimental Type 2 Diabetes in Male Rats.

    Science.gov (United States)

    Refaat, Rowaida; Sakr, Ahmed; Salama, Mona; El Sarha, Ashgan

    2016-09-01

    Preclinical Research The majority of studies on vildagliptin and pioglitazone have focused on their combination in glycemic control. The aim of the present study was to investigate their effects in combination on (i) hyperglycemia-induced oxidative stress and inflammation and (ii) on organs involved in the pathophysiology of diabetes, pancreas, kidney and liver. Type 2 diabetes was induced using low-dose streptozotocin in male Wistar rats. Diabetic rats were treated for 4 weeks, with vildagliptin (10 mg/kg/day), pioglitazone (10 mg/kg/day) and their combination. Diabetic rats showed elevated fasting serum glucose, fasting serum insulin, serum transaminases together with a deleterious lipid profile and elevated serum creatinine and urea concentrations. Serum levels of the inflammatory markers tumor necrosis factor-α (TNF-α) and nitrite/nitrate were also elevated compared to normal rats. Oxidative stress was manifested by lowered hepatic reduced glutathione (GSH) and increased malondialdehyde (MDA) levels. Pancreatic sections from diabetic rats showed degenerated islets with poorly maintained architecture that was prevented by drug treatment. Pioglitazone was generally more effective than vildagliptin in the studied parameters except for the lipid profile where the effect of both drugs was comparable and for the liver enzymes and renal parameters where vildagliptin was more effective. The combination of vildagliptin and pioglitazone produced superior effects than either drug alone. Drug Dev Res 77 : 251-257, 2016. © 2016 Wiley Periodicals, Inc.

  18. Usage of pioglitazone at Medanta, the Medicity

    Directory of Open Access Journals (Sweden)

    Ambrish Mithal

    2014-01-01

    Full Text Available Pioglitazone improves glycemic control by acting as an insulin sensitizer and is used in the management of Type 2 diabetes mellitus. Pioglitazone has recently been at the center of a controversy with regards to its safety. There is no clear consensus on how, when and in what dose the drug should be used in the management of diabetes. We have summarized our strategy on pioglitazone use in Type 2 diabetes in a large private tertiary care center - Medanta, the Medicity- which may help in generating further thought about positioning of this anti-diabetic molecule. We use pioglitazone as the fourth in the pecking order of oral anti-diabetic agents. We typically use pioglitazone in a dose of 15 mg/day. We avoid using pioglitazone with insulin. We do not use pioglitazone under following situations: In the presence of significant or proven cardiac disease, in patients who are struggling with their weight or need to lose weight, in patients at high risk for osteoporotic fractures, in patients with macular edema, in patients with pre-existing bladder cancer and would discontinue in case hematuria or any other symptom of bladder cancer develops. We continue to use the drug in patients well controlled on it without any evident side-effects or contraindications.

  19. Usage of pioglitazone at Medanta, the Medicity.

    Science.gov (United States)

    Mithal, Ambrish; Kaur, Parjeet; Bansal, Beena; Mishra, Sunil Kumar; Wasir, Jasjeet S; Jevalikar, Ganesh; Mahendru, Shama

    2014-01-01

    Pioglitazone improves glycemic control by acting as an insulin sensitizer and is used in the management of Type 2 diabetes mellitus. Pioglitazone has recently been at the center of a controversy with regards to its safety. There is no clear consensus on how, when and in what dose the drug should be used in the management of diabetes. We have summarized our strategy on pioglitazone use in Type 2 diabetes in a large private tertiary care center - Medanta, the Medicity- which may help in generating further thought about positioning of this anti-diabetic molecule. We use pioglitazone as the fourth in the pecking order of oral anti-diabetic agents. We typically use pioglitazone in a dose of 15 mg/day. We avoid using pioglitazone with insulin. We do not use pioglitazone under following situations: In the presence of significant or proven cardiac disease, in patients who are struggling with their weight or need to lose weight, in patients at high risk for osteoporotic fractures, in patients with macular edema, in patients with pre-existing bladder cancer and would discontinue in case hematuria or any other symptom of bladder cancer develops. We continue to use the drug in patients well controlled on it without any evident side-effects or contraindications.

  20. Pioglitazone and alogliptin combination therapy in type 2 diabetes: a pathophysiologically sound treatment.

    Science.gov (United States)

    Triplitt, Curtis; Cersosimo, Eugenio; DeFronzo, Ralph A

    2010-09-07

    Insulin resistance and islet (beta and alpha) cell dysfunction are major pathophysiologic abnormalities in type 2 diabetes mellitus (T2DM). Pioglitazone is a potent insulin sensitizer, improves pancreatic beta cell function and has been shown in several outcome trials to lower the risk of atherosclerotic and cardiovascular events. Glucagon-like peptide-1 deficiency/resistance contributes to islet cell dysfunction by impairing insulin secretion and increasing glucagon secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors improve pancreatic islet function by augmenting glucose-dependent insulin secretion and decreasing elevated plasma glucagon levels. Alogliptin is a new DPP-4 inhibitor that reduces glycosylated hemoglobin (HbA(1c)), is weight neutral, has an excellent safety profile, and can be used in combination with oral agents and insulin. Alogliptin has a low risk of hypoglycemia, and serious adverse events are uncommon. An alogliptin-pioglitazone combination is advantageous because it addresses both insulin resistance and islet dysfunction in T2DM. HbA(1c) reductions are significantly greater than with either monotherapy. This once-daily oral combination medication does not increase the risk of hypoglycemia, and tolerability and discontinuation rates do not differ significantly from either monotherapy. Importantly, measures of beta cell function and health are improved beyond that observed with either monotherapy, potentially improving durability of HbA(1c) reduction. The alogliptin-pioglitazone combination represents a pathophysiologically sound treatment of T2DM.

  1. Effects of pioglitazone in familial combined hyperlipidaemia.

    NARCIS (Netherlands)

    Abbink-Zandbergen, E.J.; Graaf, J. de; Haan, J.H.A. de; Heerschap, A.; Stalenhoef, A.F.H.; Tack, C.J.J.

    2006-01-01

    OBJECTIVES: Familial combined hyperlipidaemia (FCH) is associated with insulin resistance. We hypothesized that pioglitazone treatment of FCH patients might increase insulin sensitivity, but may also improve serum lipid levels, body fat distribution, intramyocellular lipids (IMCL) and endothelial fu

  2. Pioglitazone: a valuable component of combination therapy for type 2 diabetes mellitus.

    Science.gov (United States)

    Papanas, Nikolaos; Katsiki, Niki; Hatzitolios, Apostolos I; Maltezos, Efstratios

    2011-07-01

    Several classes of drugs have been developed to treat type 2 diabetes mellitus (T2DM). Pioglitazone is now the only thiazolidinedione approved for the treatment of T2DM and can be administered in combination with metformin, sulfonylureas, exenatide, dipeptidyl peptidase 4 (DPP-4) inhibitors or insulin. It improves glycemic control with an extremely low incidence of hypoglycemia. In addition to reducing insulin resistance, it may also improve pancreatic beta-cell secretory function. Moreover, it exhibits a variety of favorable pleiotropic effects. The latter include anti-inflammatory, antioxidant, vasoprotective, antihypertensive and hypolipidemic actions. Finally, this agent has been shown to improve experimental diabetic neuropathy and alleviate neuropathic pain, as well as decreasing urinary albumin excretion in patients with diabetes. Thus, pioglitazone emerges as a valuable hypoglycemic agent for combination therapy in T2DM. Importantly, however, patients should be appropriately selected, especially to avoid those with heart failure, in order to minimize adverse events attributable to water retention.

  3. Modified duodenum-preserving pancreatic head resection in treatment of patients with chronic pancreatitis%改良保留十二指肠胰头切除术治疗慢性胰腺炎的疗效分析

    Institute of Scientific and Technical Information of China (English)

    魏洪吉; 吴河水; 熊炯炘; 陶京; 周峰; 王春友

    2011-01-01

    目的:观察改良保留十二指肠的胰头切除术(改良Beger手术)对伴胰头炎性肿块的慢性胰腺炎病人的治疗效果.方法:回顾性分析自2004年1月至2010年12月,在我院胰腺外科接受改良Beger手术治疗的51例伴胰头炎性肿块的慢性胰腺炎病人的临床资料,并对病人术后疼痛症状、生活质量及内分泌功能等进行随访.结果:无手术死亡病例,术后并发症发生率为15.7%,其中胰漏3例,胆漏2例,十二指肠漏l例,腹腔出血1例,切口裂开1例.术后6个月,病人疼痛得到明显缓解,EORTC QLQ-C30疼痛评分由(64.3±5.8)降至(12.5±3.7)(P<0.01),生活质量获显著提高,GLQI生活质量评分由(70.1±5.8)增至(86.4±6.6)(P<0.01);病人内分泌功能未受影响,无新增糖尿病病例.结论:采用改良Beger手术治疗伴胰头炎性肿块的慢性胰腺炎是安全、有效的.%Objective To observe the therapeutic efficacy of a modified duodenum-preserving pancreatic head resection procedure in the treatment of patients with chronic pancreatitis and an inflammatory mass in the head of the pancreas. Methods From Jan 2004 to Dec 2010, a modified duodenum-preserving pancreatic head resection procedure was performed in fifty-one patients with chronic pancreatitis and an inflammatory mass in the head of the pancreas. The pain scale in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Gastrointestinal Quality of Life Index (GLQI) questionnaire, and oral glucose tolerance test (OGTT) were used to evaluate the changes in preoperative and postoperative pain symptomatology, quality of life, and endocrine function of the patients correspondingly. Results There was no hospital mortality. The overall postoperative incidence rate of complications was 13.7%, including pancreatic fistula in 3 cases, bile leakage in 2 cases, duodenal fistula in 1 case, intraabdominal bleeding in 1 case and wound disruption in 1 case

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

    Directory of Open Access Journals (Sweden)

    Catalina Carrasco-Pozo

    2017-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    Carrasco-Pozo, Catalina; Tan, Kah Ni; Gotteland, Martin; Borges, Karin

    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.

  6. Vildagliptin preserves the mass and function of pancreatic β cells via the developmental regulation and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes.

    Science.gov (United States)

    Hamamoto, S; Kanda, Y; Shimoda, M; Tatsumi, F; Kohara, K; Tawaramoto, K; Hashiramoto, M; Kaku, K

    2013-02-01

    We investigated the molecular mechanisms by which vildagliptin preserved pancreatic β cell mass and function. Morphological, biochemical and gene expression profiles of the pancreatic islets were investigated in male KK-A(y) -TaJcl(KK-A(y) ) and C57BL/6JJcl (B6) mice aged 8 weeks which received either vildagliptin or a vehicle for 4 weeks. Body weight, food intake, fasting blood glucose, plasma insulin and active glucagon-like peptide-1 were unchanged with vildagliptin treatment in both mice. In KK-A(y) mice treated with vildagliptin, increased plasma triglyceride (TG) level and islet TG content were decreased, insulin sensitivity significantly improved, and the glucose tolerance ameliorated with increases in plasma insulin levels. Furthermore, vildagliptin increased glucose-stimulated insulin secretion, islet insulin content and pancreatic β cell mass in both strains. By vildagliptin, the expression of genes involved in cell differentiation/proliferation was upregulated in both strains, those related to apoptosis, endoplasmic reticulum stress and lipid synthesis was decreased and those related to anti-apoptosis and anti-oxidative stress was upregulated, in KK-A(y) mice. The morphological results were consistent with the gene expression profiles. Vildagliptin increases β cell mass by not only directly affecting cell kinetics but also by indirectly reducing cell apoptosis, oxidative stress and endoplasmic reticulum stress in diabetic mice. © 2012 Blackwell Publishing Ltd.

  7. Pioglitazone

    Science.gov (United States)

    ... following: atorvastatin (Lipitor, in Caduet), gemfibrozil (Lopid), hormonal contraceptives (birth control pills, patches, rings, implants, and injections), insulin or other medications to treat ...

  8. Investigation of the antibacterial activity of pioglitazone

    Directory of Open Access Journals (Sweden)

    Alzoubi KH

    2011-09-01

    Full Text Available Majed M Masadeh1, Nizar M Mhaidat2, Sayer I Al-Azzam2, Karem H Alzoubi21Department of Pharmaceutical Technology; 2Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, JordanPurpose: To evaluate the antibacterial potential of pioglitazone, a member of the thiazolidinediones class of drugs, against Gram-positive (Streptococcus pneumoniae and Gram-negative (Escherichia coli and Klebsiella pneumoniae bacteria.Methods: Susceptibility testing was done using the antibiotic disk diffusion method and the minimal inhibitory concentration (MIC of pioglitazone was measured according to the broth micro incubation standard method.Results: Pioglitazone induced a dose-dependent antibacterial activity in which the optimal concentration was 80 µM. Furthermore, results indicated that while E. coli was sensitive (MIC = 31.25 ± 3.87 mg/L to pioglitazone-induced cytotoxicity, S. pneumoniae and K. pneumoniae were resistant (MIC = 62.5 ± 3.77 mg/L and MIC = 62.5 ± 4.14 mg/L, respectively. Moreover, pretreatment of bacteria with a suboptimal concentration of pioglitazone (40 µM before adding amoxicillin, cephalexin, co-trimoxazole, or ciprofloxacin enhanced the antibacterial activity of all agents except co-trimoxazole. This enhancing effect was particularly seen against K. pneumoniae.Conclusion: These results indicate the possibility of a new and potentially important pioglitazone effect and the authors’ ongoing studies aim to illustrate the mechanism(s by which this antibacterial effect is induced.Keywords: pioglitazone, susceptibility testing, antibiotics, diabetes 

  9. Pioglitazone:A review of analytical methods

    Institute of Scientific and Technical Information of China (English)

    N. Satheeshkumar; S. Shantikumar; R. Srinivas

    2014-01-01

    Pioglitazone is an oral anti-hyperglycemic agent. It is used for the treatment of diabetes mellitus type 2. It selectively stimulates nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma). It was the tenth-best-selling drug in the U.S. in 2008. This article examines published analytical methods reported so far in the literature for the determination of pioglitazone in biological samples and pharmaceutical formulations. They include various techniques like electrochemical methods, spectrophotometry, capillary electrophoresis, high-performance liquid chromatography, liquid chromatography-electrospray ionization-tandem mass spectrometry and high-performance thin layer chromatography.

  10. Pioglitazone improves reversal learning and exerts mixed cerebrovascular effects in a mouse model of Alzheimer's disease with combined amyloid-β and cerebrovascular pathology.

    Directory of Open Access Journals (Sweden)

    Panayiota Papadopoulos

    Full Text Available Animal models of Alzheimer's disease (AD are invaluable in dissecting the pathogenic mechanisms and assessing the efficacy of potential new therapies. Here, we used the peroxisome proliferator-activated receptor gamma agonist pioglitazone in an attempt to rescue the pathogenic phenotype in adult (12 months and aged (>18 months bitransgenic A/T mice that overexpress a mutated human amyloid precursor protein (APPSwe,Ind and a constitutively active form of transforming growth factor-β1 (TGF-β1. A/T mice recapitulate the AD-related cognitive deficits, amyloid beta (Aβ and cerebrovascular pathologies, as well as the altered metabolic and vascular coupling responses to increased neuronal activity. Pioglitazone normalized neurometabolic and neurovascular coupling responses to sensory stimulation, and reduced cortical astroglial and hippocampal microglial activation in both age groups. Spatial learning and memory deficits in the Morris water maze were not rescued by pioglitazone, but reversal learning was improved in the adult cohort notwithstanding a progressing Aβ pathology. While pioglitazone preserved the constitutive nitric oxide synthesis in the vessel wall, it unexpectedly failed to restore cerebrovascular reactivity in A/T mice and even exacerbated the dilatory deficits. These data demonstrate pioglitazone's efficacy on selective AD hallmarks in a complex AD mouse model of comorbid amyloidosis and cerebrovascular pathology. They further suggest a potential benefit of pioglitazone in managing neuroinflammation, cerebral perfusion and glucose metabolism in AD patients devoid of cerebrovascular pathology.

  11. The effect of pioglitazone and resistance training on body composition in older men and women undergoing hypocaloric weight loss.

    Science.gov (United States)

    Shea, M Kyla; Nicklas, Barbara J; Marsh, Anthony P; Houston, Denise K; Miller, Gary D; Isom, Scott; Miller, Michael E; Carr, J Jeffrey; Lyles, Mary F; Harris, Tamara B; Kritchevsky, Stephen B

    2011-08-01

    Age-related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPARγ-agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65-79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m(2)) and women (n = 40, BMI = 33.3 ± 4.9 kg/m(2)) during weight loss. All participants underwent a 16-week hypocaloric weight-loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow-up using computed tomography (CT). Lean mass was measured using dual X-ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (-1,160 vs. -647 cm(3), P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (-104 vs. -298 cm(3), P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: -43 vs. -88 cm(3), P = 0.005; women: -34 vs. -59 cm(3), P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.

  12. [A Case of Von Hippel-Lindau Disease with Nonfunctioning Pancreatic Neuroendocrine Tumors Treated by Duodenum-Preserving Resection of the Head of the Pancreas and Spleen-Preserving Resection of the Tail of the Pancreas].

    Science.gov (United States)

    Umehara, Yutaka; Umehara, Minoru; Tokura, Tomohisa; Yachi, Takafumi; Takahashi, Kenichi; Morita, Takayuki; Hakamada, Kenichi

    2015-10-01

    A 26-year-old woman presented to our department with a diagnosis of multiple nonfunctioning pancreatic neuroendocrine tumors. She had a family history of pheochromocytoma and a medical history of bilateral adrenalectomy for pheochromocytoma at the age of 25 years. During follow-up treatment for adrenal insufficiency after the surgery, highly enhanced tumors in the pancreas were detected on contrast-enhanced CT. Other examinations found that the patient did not satisfy the clinical criteria for von Hippel-Lindau (VHL) disease. Considering her age and risk of developing multiple heterotopic and heterochronous tumors, we performed a duodenum-preserving resection of the head of the pancreas and spleen-preserving resection of the tail of the pancreas with informed consent. The histopathological findings revealed that all of the tumors were NET G1. She underwent genetic testing postoperatively and was diagnosed with VHL disease. This diagnosis meant that we were able to create an optimal treatment plan for the patient. If a tumor predisposition syndrome is suspected, VHL disease should be borne in mind and genetic testing after genetic counseling should be duly considered.

  13. Pioglitazone-induced Pulmonary Injury in a Very Elderly Patient.

    Science.gov (United States)

    Katayama, Kohta; Kumagai, Ryo; Isono, Momoko; Fujihara, Kazuya; Yagyu, Hiroaki; Ohara, Gen; Kagohashi, Katsunori; Satoh, Hiroaki

    2016-01-01

    An 85-year-old woman with diabetes mellitus was admitted to our hospital due to progressive dyspnea. Two months previously, pioglitazone had been newly prescribed for diabetes management. Bilateral ground-glass opacities and progressive respiratory deterioration suggested respiratory failure due to a drug-induced lung injury. With discontinuation of pioglitazone and the administration of a corticosteroid, an improvement in her respiratory condition was achieved, although sequelae remained in some areas of the lungs. Results of drug-induced lymphocyte stimulation tests were positive for pioglitazone. Resumption of other drugs did not reinduce the lung injury. Therefore, a diagnosis of pioglitazone-induced lung injury was made. Although pioglitazone-induced lung injury is very rare, clinicians should keep it in mind when pioglitazone is used.

  14. Acute pancreatitis

    Science.gov (United States)

    ... its blood vessels. This problem is called acute pancreatitis. Acute pancreatitis affects men more often than women. Certain ... pancreatitis; Pancreas - inflammation Images Digestive system Endocrine glands Pancreatitis, acute - CT scan Pancreatitis - series References Forsmark CE. Pancreatitis. ...

  15. Small Molecule Kaempferol Promotes Insulin Sensitivity and Preserved Pancreatic β -Cell Mass in Middle-Aged Obese Diabetic Mice.

    Science.gov (United States)

    Alkhalidy, Hana; Moore, William; Zhang, Yanling; McMillan, Ryan; Wang, Aihua; Ali, Mostafa; Suh, Kyung-Shin; Zhen, Wei; Cheng, Zhiyong; Jia, Zhenquan; Hulver, Matthew; Liu, Dongmin

    2015-01-01

    Insulin resistance and a progressive decline in functional β-cell mass are hallmarks of developing type 2 diabetes (T2D). Thus, searching for natural, low-cost compounds to target these two defects could be a promising strategy to prevent the pathogenesis of T2D. Here, we show that dietary intake of flavonol kaempferol (0.05% in the diet) significantly ameliorated hyperglycemia, hyperinsulinemia, and circulating lipid profile, which were associated with the improved peripheral insulin sensitivity in middle-aged obese mice fed a high-fat (HF) diet. Kaempferol treatment reversed HF diet impaired glucose transport-4 (Glut4) and AMP-dependent protein kinase (AMPK) expression in both muscle and adipose tissues from obese mice. In vitro, kaempferol increased lipolysis and prevented high fatty acid-impaired glucose uptake, glycogen synthesis, AMPK activity, and Glut4 expression in skeletal muscle cells. Using another mouse model of T2D generated by HF diet feeding and low doses of streptozotocin injection, we found that kaempferol treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in obese diabetic mice, which are associated with the improved islet β-cell mass. These results demonstrate that kaempferol may be a naturally occurring anti-diabetic agent by improving peripheral insulin sensitivity and protecting against pancreatic β-cell dysfunction.

  16. The impact of pioglitazone on bladder cancer and cardiovascular events.

    Science.gov (United States)

    Lee, Esther J; Marcy, Todd R

    2014-08-01

    Type 2 diabetes mellitus (T2DM) is a chronic condition with increasing prevalence and severe complications. Thiazolidinediones have been marketed since 1997 and are effective glucose-lowering drugs, but individual drugs within the class have been linked to serious adverse effects that resulted in the removal of troglitazone from the market, restrictions to rosiglitazone's use, and a warning added to pioglitazone's label. In 2007, a meta-analysis linked rosiglitazone to myocardial infarction (MI). Pioglitazone does not appear to share this risk. To the contrary, pioglitazone may reduce risk for MI. However, retrospective evaluations have increasingly linked pioglitazone to a higher risk of bladder cancer that appears to be time- and dose-dependent. Pioglitazone remains a medication appropriate for consideration in the management of T2DM; however, clinicians and patients should weigh its risks compared with alternatives, with a regular review of risks.

  17. Hereditary Pancreatitis

    Science.gov (United States)

    ... alcohol is a known risk factor for both acute and chronic pancreatitis. Therefore it is recommended that all HP patients ... Pancreatitis Patient Info Animated Pancreas Patient Pancreatic Cancer Chronic Pancreatitis Acute Pancreatitis Research Research Grant Application Research History Grant ...

  18. Pancreatitis - discharge

    Science.gov (United States)

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

  19. Efficacy of modified duodenum-preserving pancreatic head resection for chronic pancreatitis%改良保留十二指肠胰头切除术治疗慢性胰腺炎的临床疗效

    Institute of Scientific and Technical Information of China (English)

    杨明; 赵刚; 吴河水; 王春友

    2014-01-01

    Objective To investigate the efficacy of a modified duodenum-preserving pancreatic head resection (DPPHR) for the treatment of chronic pancreatitis.Methods The clinical data of 109 patients with chronic pancreatitis who received modified DPPHR at the Union Hospital of Huazhong University of Science and Technology from January 2004 to June 2013 were retrospectively analyzed.Of the 109 patients,66 were with mass in the head of the pancreas,29 were with calcification of the head of the pancreas,14 were with atrophy of the head of the pancreas and stones in the main pancreatic duct.The level of glucose of 56 patients were normal,34 patients had glucose tolerance abnormalities and 19 were complicated with diabetes mellitus.Modified DPPHR was carried out after confirming the diagnosis of chronic pancreatitis and excluding the malignancies by frozen pathological examination.The head of the pancreas was completely resected.The posterior pancreaticoduodenal aortic arch running parallel to the duodenum was preserved to guarantee the blood supply to the remaining duodenum.A thin sheet of the pancreatic tissue behind the intrapancreatic common bile duct and between the common bile duct and the duodenum was preserved to guarantee the blood supply to the common bile duct.The gastrointestinal tract was reconstructed with an anastomosis of the distal pancreas and the jejunum and an end-to-en anastomosis of the proximal jejunum and the distal jejunum.Patients were followed up via out-patient examination to learn the frequency of abdominal pain,analgesics usage and the endocrine function.The pain scale,life quality and endocrine function were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30),Gastrointestinal Quality of Life Index (GLQI) questionnaire,and oral glucose tolerance test (OGTT),respectively.Patients were followed up till January 2014.The measurement data and the count data were analyzed using the t

  20. The PPAR-γ agonist pioglitazone modulates inflammation and induces neuroprotection in parkinsonian monkeys

    Directory of Open Access Journals (Sweden)

    Swanson Christine R

    2011-08-01

    Full Text Available Abstract Background Activation of the peroxisome proliferator-activated receptor gamma (PPAR-γ has been proposed as a possible neuroprotective strategy to slow down the progression of early Parkinson's disease (PD. Here we report preclinical data on the use of the PPAR-γ agonist pioglitazone (Actos®; Takeda Pharmaceuticals Ltd. in a paradigm resembling early PD in nonhuman primates. Methods Rhesus monkeys that were trained to perform a battery of behavioral tests received a single intracarotid arterial injection of 20 ml of saline containing 3 mg of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP. Twenty-four hours later the monkeys were assessed using a clinical rating scale, matched accordingly to disability, randomly assigned to one of three groups [placebo (n = 5, 2.5 (n = 6 or 5 (n = 5 mg/kg of pioglitazone] and their treatments started. Three months after daily oral dosing, the animals were necropsied. Results We observed significant improvements in clinical rating score (P = 0.02 in the animals treated with 5 mg/kg compared to placebo. Behavioral recovery was associated with preservation of nigrostriatal dopaminergic markers, observed as higher tyrosine hydroxylase (TH putaminal optical density (P = 0.011, higher stereological cell counts of TH-ir (P = 0.02 and vesicular monoamine transporter-2 (VMAT-2-ir nigral neurons (P = 0.006. Stereological cell counts of Nissl stained nigral neurons confirmed neuroprotection (P = 0.017. Pioglitazone-treated monkeys also showed a dose-dependent modulation of CD68-ir inflammatory cells, that was significantly decreased for 5 mg/kg treated animals compared to placebo (P = 0.018. A separate experiment to assess CSF penetration of pioglitazone revealed that 5 mg/kg p.o. induced consistently higher levels than 2.5 mg/kg and 7.5 mg/kg. p.o. Conclusions Our results indicate that oral administration of pioglitazone is neuroprotective when administered early after inducing a

  1. Pioglitazone Improves Survival In Patients With Cancer: The Hypothesis

    Directory of Open Access Journals (Sweden)

    Banshi Saboo

    2015-12-01

    Full Text Available Pioglitazone is currently the only thiazolidinedione approved by regulatory agencies worldwide for the treatment of type 2 diabetes mellitus (T2DM. The use of pioglitazone in patients with T2DM has been limited because earlier studies showed moderate weight gain and an increased incidence of heart failure, osteoporotic fractures, and bladder cancer. However, new studies have shown that pioglitazone improves both systolic and diastolic left ventricular function and that there is no association between pioglitazone and bladder cancer. Furthermore, pioglitazone is associated with a reduced risk of all-cause mortality in patients with T2DM. Pioglitazone was also found to reduce the incidence of lung, head and neck, breast, colorectal, and hepatocellular cancer. There is tremendous preclinical evidence that links thiazolidinediones with anti-cancer effects. Three possible mechanisms of anti-proliferative effects induced by peroxisome proliferator activated receptor gamma (PPARG agonists emerge: 1 activation of PPARG and epidermal growth factor receptor, which actives several intracellular pathways involved in carcinogenesis; 2 increase in serum adiponectin levels and decrease in serum leptin levels, which are associated with lower cancer risk and more favorable outcomes in patients with cancer; 3 modulate insulin-like growth factor 1 (IGF-1 receptor signaling by decreasing IGF-1 levels and increasing the expression of IGF binding protein 1. To date, there are no prospective, placebo-controlled trials that have analyzed the efficacy of pioglitazone in chemotherapy and chemoprevention. Only one ongoing study has shown that pioglitazone has an excellent capability of eradicating quiescent leukemia stem cells in patients with chronic myeloid leukemia and achieving a complete molecular response. Current evidence supports our theory that future case-control studies examining pioglitazone as chemotherapy, or adjuvant chemotherapy, should be performed in

  2. [Chronic pancreatitis, acute pancreatitis].

    Science.gov (United States)

    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.

  3. Protective effect of pioglitazone on cardiomyocyte apoptosis in low-dose streptozotocin & high-fat diet-induced type-2 diabetes in rats

    Directory of Open Access Journals (Sweden)

    Uma Bhandari

    2015-01-01

    Full Text Available Background & objectives: Cardiomyocyte apoptosis is one of the pathologic phenomena associated with diabetes and related conditions including obesity, insulin resistance and hyperlipidaemia. In the present study, the protective effects of pioglitazone on cardiomyocyte apoptosis was evaluated in experimental diabetes induced by low dose of streptozoticin (STZ combined with high fat diet (HFD in rats. Methods: Male Wistar rats (150-200 g were injected with low-dose STZ (45 mg/kg, i.v., single dose and orally fed with a HFD (20 g/day/rat for a period of 28 days and simultaneously treated with pioglitazone (20 mg/kg/p.o. for a period of 21 days (from 8 th day to 28 th day. On 29 th day blood was collected, serum separated and used for biochemical parameters. Heart tissue was used for cardiomyocyte apoptosis measurement and also for histopathological examination. Results: Pioglitazone treatment resulted in a decrease in cardiomyocyte apoptosis as revealed by a decrease in cardiac caspase-3, lactate dehydrogenase (LDH levels and DNA fragmentation, and an increase in Na+K+ATPase levels in diabetic rats. Cardiac histology of diabetic control rats showed dense focal fatty infiltration in the myocardial cells whereas normal architecture with regular morphology and well preserved cytoplasm was observed with pioglitazone treatment. Pioglitazone treatment significantly reduced the heart rate, mean arterial blood pressure, body mass index (BMI and levels of serum glucose, leptin, insulin, HOMA-IR, total cholesterol (TC and triglycerides (TGs, apoliproprotein-B glycosylated haemoglobin (HbA1c levels and atherogenic index, and increased the levels of serum high density lipoprotein cholesterol (HDL-C and cardiac antioxidant enzymes. Interpretation & conclusions: The present study results suggest that pioglitazone possesses cardiac anti-apoptotic potential in diabetic rat model and can be further explored for its use for treatment of diabetic cardiomyopathy.

  4. An experimental study of pioglitazone in treating vascular dementia

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To compare the therapeutic effects of different doses of pioglitazone,a kind of peroxisome proliferator-activated receptor γ(PPARγ)agonist,on vascular dementia and explore how pioglitazone affects cerebral ischemia.Methods Modified Pulsinelli's vessel ligation was used to establish a vascular dementia model in rats.Recognition,learning and memory were evaluated by Morris's water maze test.Immunoenzyme staining was used to determine the number of nerve cells.Immunofluorescence double-staining was u...

  5. Pioglitazone use and the risk of bladder cancer.

    Science.gov (United States)

    Kuo, Hsin-Wei; Tiao, Mao-Meng; Ho, Shu-Chen; Yang, Chun-Yuh

    2014-02-01

    This study aimed to identify the risk association between pioglitazone exposure and bladder cancer. A nested case-control study was performed using a representative database randomly sampled from National Health Insurance enrollees. The source cohort consisted of newly diagnosed diabetic patients from 1997 to 2009. Cases were identified as those with a diagnosis of bladder cancer from 2002 to 2009. For each case, four matched control individuals were randomly selected. A multiple logistic regression model was used to estimate the relative magnitude of risk in relation to the use of pioglitazone. In total, 259 cases and 1036 controls were identified. The prevalent use of pioglitazone is similar in cases and controls (adjusted odds ratio, 1.20; 95% confidence interval, 0.58-2.49). Compared to nonusers, these values were 1.08 (0.41-2.88) for those with cumulative pioglitazone use ≤ 8268 mg and 1.35 (0.48-3.79) for those with cumulative pioglitazone use > 8268 mg. This study does not provide support for the risk association between pioglitazone exposure and bladder cancer. Further confirmation is needed due to the limitation of small case number with relatively shorter exposure duration and lower cumulative dose.

  6. Treatment of acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Al-Mofleh Ibrahim

    1998-01-01

    Full Text Available There is no specific treatment for acute pancreatitis. Majority of patients with acute pancreatitis respond to medical therapy. Supportive measures and close observations represent the cornerstone of the medical therapy. Failure to respond to medical treatment may indicate choledocholithiasis or infected necrosis. Endoscopic papillotomy with stone retrieval is beneficial in patients with severe biliary pancreatitis. Image-guided fine needle aspiration and bacteriological examination of aspirate is reliable in detecting infection and deliniating causative pathogen. Surgical debridement is the method of choice for treatment of infected necrosis. In contrast, in pancreatic abscess, surgery is preserved for those, who do not respond to percutaneous drainage combined with antibiotics. The benefit of antisecretory and antiproteolytic agents is debatable. A combination of antioxidants, calcium channel antagonists and antibiotics may play a major role in the treatment of acute pancreatitis in the future.

  7. Toxicological evaluation of subchronic use of pioglitazone in mice

    Directory of Open Access Journals (Sweden)

    Said Said Elshama

    2016-07-01

    Full Text Available Objective(s: Pioglitazone (Actos is one of the most controversial recent oral antidiabetic drugs. It was originally authorized in the European Union in 2000, and approved as an oral monotherapy for overweight second type of diabetic patients in 2002. It belongs to the thiazolidinedione group which some of its members have been withdrawn from the market due to the hepatotoxicity or cardiotoxicity effects.This studyinvestigates sub-chronic use of pioglitazone induced toxicity in mice by the assessment of renal and liver function tests, cardiac enzymes, and some hematological indices with histological changes of liver, kidney, heart, and bladder. Materials and Methods: 120 albino mice were divided into four groups; 30 in each. The first group (control received water, second (diabetic group received alloxan only, while the third and the fourth groups received alloxan with 200 and 400 mg/kg/day of pioglitazone, respectively for 90 days. Results: Prolonged use of pioglitazone induced significant abnormalities of hepatic, renal, and cardiac biomarkers and some hematological indices associated with histopathological changes in the liver, kidney, heart, and bladder that increased based on administered dose. Conclusion: Subchronic use of pioglitazone leads to hepatic, renal, cardiac, hematological, and bladder affection depending on the applied dose.

  8. 保留十二指肠的胰头切除与保留幽门的胰十二指肠切除治疗胰头肿块型胰腺炎的Meta分析%A meta-analysis on surgical treatments for chronic pancreatitis: duodenum-preserving pancreatic head resection versus pylorus-preserving pancreaticoduodenectomy

    Institute of Scientific and Technical Information of China (English)

    汪超; 黄强; 林先盛; 刘臣海; 杨骥

    2015-01-01

    Objective To compare the safety and effectiveness of duodenum-preserving pancreatic head resection (DPPHR) with pylorus-preserving pancreaticoduodenectomy (PPPD) in the treatment of chronic pancreatitis with a pancreatic head mass.Methods Medline,Biosis,Cochrane Library,Science Citation Index Database,CBM Database,Wan Fang and CNKI were searched systematically.The bias risk of the included trials was assessed according to the assessing tools as suggested by the Cochrane Handbook.Review Manage 5.2 was used to perform the statistical analysis.Results 7 RCTs with 226 patients were included in the meta-analysis which showed that there were no significant differences between PPPD and DPPHR in overall postoperative morbidity,postoperative hospital stay,complete pain relief,pancreatic fistula,exocrine insufficiency,symptom score at 5 to 7-year follow-up,and quality of life score at 14 to 15-year follow-up (P > 0.05).While DPPHR had significant superiorities in operation time,blood replacement,delayed gastric emptying,occupational rehabilitation after the operations,weight gain,quality of life score at 1 to 2-year follow-up,symptom score at 5 to 7-year follow-up,and physical functioning score at 14 to 15-year follow-up.Conclusions DPPHR is more favourable than PPPD in reducing the use of blood replacement,shortening operation time,delayed gastric emptying,occupational rehabilitation after the operations,weight gain,physical functioning,and in improving quality of life of patients.%目的 探讨保留十二指肠的胰头切除术(DPPHR)与保留幽门的胰十二指肠切除术(PPPD)治疗胰头肿块型胰腺炎的安全性和有效性.方法 系统检索Medline、Biosis、The Cochrane Library、Science Citation Index Database、中国生物医学文献数据库、中国期刊全文数据库、万方数据库、维普中文科技期刊数据库.选取相关临床随机对照试验,参考Cochrane Handbook的偏倚风险评估工具评估偏倚风险.应用Review Manager

  9. Spectrophotometric estimation of pioglitazone hydrochloride in tablet dosage form

    Directory of Open Access Journals (Sweden)

    Basniwal Pawan

    2008-01-01

    Full Text Available Two simple, rapid, and precise methods - linear regression equation (LRE and standard absorptivity - were developed and validated for the estimation of pioglitazone hydrochloride in tablet dosage form. The maximum absorbance (lmax of pioglitazone hydrochloride was found to be 269.8 nm in methanol:water:hydrochloric acid (250:250:1. Beer-Lambert law was obeyed in the concentration range of 10-50 µg/ml, and the standard absorptivity was found to be 253.97 dl/g/cm. Both the methods were validated for linearity, accuracy, precision (days, analysts, and instrument variation, and robustness (solvent composition. The numerical values for all parameters lie within the acceptable limits. Pioglitazone hydrochloride was estimated in the range of 99.58-99.97% by LRE method and 100.25-100.75% by standard absorptivity method. At 99% confidence limit, the F-test value for the methods was found to be 1.8767.

  10. Effect of Pioglitazone on Plasma Levels of Phenytoin in Rats

    Directory of Open Access Journals (Sweden)

    Abolghasem Jouyban

    2013-10-01

    Full Text Available Introduction: Interaction between drugs represents a major clinical concern for health care professionals and their patients. Patients affected by both type 2 diabetes and epilepsy may be prescribed pioglitazone and an anti-epileptic drug such as phenytoin  concurrently. The aim of this study was to consider the interaction of pioglitazone with phenytoin in an experimental model. According to the result of this study, concurrent use of phenytoin and pioglitazone in clinic may cause therapeutic failure of phenytoin which may cause seizures and during seizures the cardiac function may be affected. Material and Methods: Two groups of rats were treated for 30 days. In group 1 (control group saline (10 ml/kg and phenytoin   (30 mg/kg were administered daily by intragastric gavage. In group 2 (test group , pioglitazone (10 mg/kg was administered daily 60 minutes before phenytoin  (30 mg/kg. Two hours after the last intragastric gavage, animals were anesthetized with ether and 2 ml of blood was drawn from the heart into a syringe containing Ethylenediaminetetraacetic (EDTA, and phenytoin  concentration in rat plasma was determined by High performance liquid chromatography (HPLC.The study consisted of 2 groups of 10 male adult Wistar rats. Results: Compared with control group, concurrent use of pioglitazone and phenytoin   was associated with significantly lower mean plasma concentrations of phenytoin : 2.08 ± 0.03  µg/ml VS 1.2 ± 0.02  µg/ml. Conclusion: Concurrent use of pioglitazone and phenytoin was associated with a significant decrease in plasma concentration of phenytoin in this experimental model. In clinic, this interaction may cause seizures and it has been shown that both cardiac and respiratory functions may affected by seizures.

  11. Impact of alogliptin and pioglitazone on lipid metabolism in islets of prediabetic and diabetic Zucker Diabetic Fatty rats.

    Science.gov (United States)

    Cai, Ying; Lydic, Todd A; Turkette, Thomas; Reid, Gavin E; Olson, L Karl

    2015-05-01

    Prolonged exposure of pancreatic beta (β) cells to elevated glucose and free fatty acids (FFA) as occurs in type 2 diabetes results in loss of β cell function and survival. In Zucker Diabetic Fatty (ZDF) rats, β cell failure is associated with increased triacylglyceride (TAG) synthesis and disruption of the glycerolipid/FFA (GL/FFA) cycle, a critical arm of glucose-stimulated insulin secretion (GSIS). The aim of this study was to determine the impact of activation of PPARγ and increased incretin action via dipeptidyl-peptidase inhibition using pioglitazone and/or alogliptin, respectively, on islet lipid metabolism in prediabetic and diabetic ZDF rats. Transition of control prediabetic ZDF rats to diabetes was associated with reduced plasma insulin levels, reduced islet insulin content and GSIS, reduced stearoyl-CoA desaturase 2 (SCD 2) expression, and increased islet TAG, diacylglyceride (DAG) and ceramides species containing saturated FA. Treatment of prediabetic ZDF rats with a combination of pioglitazone and alogliptin, but not individually, prevented the transition to diabetes and was associated with marked lowering of islet TAG and DAG levels. Pioglitazone and alogliptin, however, did not restore SCD2 expression, the degree of FA saturation in TAG, DAG or ceramides, islet insulin content, or lower ceramide levels. These findings are consistent with activation of PPARγ and increased incretin action working in concert to restore GL/FFA cycle in β cells of ZDF rats. Restoration of the GL/FFA cycle without correcting islet FA desaturation, production of islet ceramides, and/or insulin sensitivity, however, may place these islets at risk for β cell failure.

  12. Pancreatic Cancer

    Science.gov (United States)

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

  13. Pancreatic pseudocysts

    African Journals Online (AJOL)

    at formulating a classification that can be used to dictate treatment strategy ... standing of the natural history of pancreatic fluid collec- ... ring, protein plug, or stone, the ongoing pancreatic secretion ... exocrine function in chronic pancreatitis.

  14. Influence of drug transporters and stereoselectivity on the brain penetration of pioglitazone as a potential medicine against Alzheimer's disease.

    Science.gov (United States)

    Chang, Kai Lun; Pee, Hai Ning; Yang, Shili; Ho, Paul C

    2015-03-11

    Pioglitazone is currently undergoing clinical trials for treatment of Alzheimer's disease (AD). However, poor brain penetration remains an obstacle to development of the drug for such intended clinical uses. In this study, we demonstrate that the inhibition of P-glycoprotein (P-gp) significantly increases brain penetration of pioglitazone, whereas inhibition of breast cancer resistance protein (BCRP) has little effect. We also investigate the stereoselectivity of pioglitazone uptake in the brain. When mice were dosed with racemic pioglitazone, the concentration of (+)-pioglitazone was 46.6% higher than that of (-)-pioglitazone in brain tissue and 67.7% lower than that of (-)-pioglitazone in plasma. Dosing mice with pure (+)-pioglitazone led to a 76% increase in brain exposure levels compared to those from an equivalent dose of racemic pioglitazone. Pure (+)-pioglitazone was also shown to have comparable amyloid-lowering capabilities to the racemic pioglitazone in an in vitro AD model. These results suggest that P-gp may act as a stereoselective barrier to prevent pioglitazone entry into the brain. Dosing with (+)-pioglitazone instead of the racemic mixture may result in higher levels of brain exposure to pioglitazone, thus potentially improving the development of pioglitazone treatment of AD.

  15. Peripheral Biomarkers of Parkinson's Disease Progression and Pioglitazone Effects.

    Science.gov (United States)

    Simon, David K; Simuni, Tanya; Elm, Jordan; Clark-Matott, Joanne; Graebner, Allison K; Baker, Liana; Dunlop, Susan R; Emborg, Marina; Kamp, Cornelia; Morgan, John C; Ross, G Webster; Sharma, Saloni; Ravina, Bernard

    2015-01-01

    Pioglitazone, an oral hypoglycemic agent, recently failed to show promise as a disease-modifying agent in a 44-week phase 2 placebo-controlled study in 210 Parkinson's disease (PD) subjects. We analyzed peripheral biomarkers, including leukocyte PGC-1α and target gene expression, plasma interleukin 6 (IL-6) as a marker of inflammation, and urine 8-hydroxydeoxyguanosine (8OHdG) as a marker of oxidative DNA damage. Baseline or changes from baseline in biomarker levels were not associated with the rate of progression of PD. Pioglitazone did not significantly alter biomarker levels. Other agents that more effectively target these mechanisms remain of potential interest as disease modifying therapies in PD.

  16. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... 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 ...

  17. A Proteomic Comparison of Formalin-Fixed Paraffin-Embedded Pancreatic Tissue from Autoimmune Pancreatitis, Chronic Pancreatitis, and Pancreatic Cancer

    Science.gov (United States)

    Paulo, Joao A; Kadiyala, Vivek; Brizard, Scott; Banks, Peter A; Steen, Hanno; Conwell, Darwin L

    2015-01-01

    Context Formalin-fixed paraffin-embedded (FFPE) tissue is a standard for specimen preservation, and as such FFPE tissue banks are an untapped resource of histologically-characterized specimens for retrospective biomarker investigation for pancreatic disease. Objectives We use liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to compare FFPE specimens from three different diseases of the exocrine pancreas. Design We investigated the proteomic profile of FFPE pancreatic tissue from 9 archived specimens that were histologically classified as: autoimmune pancreatitis (n=3), chronic pancreatitis (n=3), and pancreatic cancer (n=3), using LC-MS/MS. Setting This is a proteomic analysis experiment of FFPE pancreatic tissue in an academic center. Patients FFPE tissue specimens were provided by Dana-Farber/Harvard Cancer Center (Boston, MA, USA). Interventions FFPE tissue specimens were collected via routine surgical resection procedures. Main outcome measures We compared proteins identified from chronic pancreatitis, autoimmune pancreatitis, and pancreatic cancer FFPE pancreatic tissue. Results We identified 386 non-redundant proteins from 9 specimens. Following our filtering criteria, 73, 29, and 53 proteins were identified exclusively in autoimmune pancreatitis, chronic pancreatitis, and pancreatic cancer specimens, respectively. Conclusions We report that differentially-expressed proteins can be identified among FFPE tissues specimens originating from individuals with different histological diagnoses. These proteins merit further confirmation with a greater number of specimens and orthogonal validation, such as immunohistochemistry. The mass spectrometry-based methodology used herein has the potential to enhance diagnostic biomarker and therapeutic target discovery, further advancing pancreatic research. PMID:23846938

  18. Effect of pioglitazone treatment on behavioral symptoms in autistic children

    Directory of Open Access Journals (Sweden)

    Edelson Stephen M

    2007-01-01

    Full Text Available Abstract Introduction Autism is complex neuro-developmental disorder which has a symptomatic diagnosis in patients characterized by disorders in language/communication, behavior, and social interactions. The exact causes for autism are largely unknown, but is has been speculated that immune and inflammatory responses, particularly those of Th2 type, may be involved. Thiazolidinediones (TZDs are agonists of the peroxisome proliferator activated receptor gamma (PPARγ, a nuclear hormone receptor which modulates insulin sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. The TZD pioglitazone (Actos is an FDA-approved PPARγ agonist used to treat type 2 diabetes, with a good safety profile, currently being tested in clinical trials of other neurological diseases including AD and MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a small cohort of children with diagnosed autism. Case description The rationale and risks of taking pioglitazone were explained to the parents, consent was obtained, and treatment was initiated at either 30 or 60 mg per day p.o. A total of 25 children (average age 7.9 ± 0.7 year old were enrolled. Safety was assessed by measurements of metabolic profiles and blood pressure; effects on behavioral symptoms were assessed by the Aberrant Behavior Checklist (ABC, which measures hyperactivity, inappropriate speech, irritability, lethargy, and stereotypy, done at baseline and after 3–4 months of treatment. Discussion and evaluation In a small cohort of autistic children, daily treatment with 30 or 60 mg p.o. pioglitazone for 3–4 months induced apparent clinical improvement without adverse events. There were no adverse effects noted and behavioral measurements revealed a significant decrease in 4 out of 5 subcategories (irritability, lethargy, stereotypy, and hyperactivity. Improved behaviors were inversely

  19. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2010-01-01

    Full Text Available Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions : Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  20. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2010-05-01

    Full Text Available Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions: Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  1. Acute and chronic pancreatitis: surgical management.

    Science.gov (United States)

    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.

  2. Pioglitazone promotes preadipocyte proliferation by downregulating p16{sup Ink4a}

    Energy Technology Data Exchange (ETDEWEB)

    Hasan, Arif U. [Department of Cardiorenal Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Ohmori, Koji, E-mail: komori@med.kagawa-u.ac.jp [Department of Cardiorenal Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Hashimoto, Takeshi [Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Kamitori, Kazuyo; Hirata, Yuko [Department of Cell Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Ishihara, Yasuhiro; Okamoto, Naoko; Noma, Takahisa [Department of Cardiorenal Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Kosaka, Hiroaki [Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Tokuda, Masaaki [Department of Cell Physiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan); Kohno, Masakazu [Department of Cardiorenal Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793 (Japan)

    2011-07-29

    Highlights: {yields} Mechanisms for preadipocyte hyperplasia by pioglitazone, a PPAR{gamma} agonist, are shown. {yields} Pioglitazone promotes cell-cycle of 3T3-L1 preadipocytes and increases their number. {yields} Pioglitazone downregulates a cyclin dependent kinase inhibitor, p16{sup Ink4a}. {yields} PPAR{gamma} transrepresses p16{sup Ink4a} gene in preadipocytes, which pioglitazone enhances. -- Abstract: Pioglitazone, a synthetic ligand of peroxisome proliferator-activated receptor (PPAR){gamma}, causes preadipocyte proliferation through a mechanism which still remains elusive. Here, to address the mechanism, we investigated the effects of PPAR{gamma} and pioglitazone on the kinetics of cyclin-dependent kinase inhibitors, especially with p16{sup Ink4a} (p16) centered, by employing 3T3-L1 preadipocytes. Pioglitazone promoted preadipocyte proliferation by increasing S and G{sub 2}/M cell-cycle entry, which was accompanied by decreased p16 mRNA expression. PPAR{gamma} overexpression along with the luciferase reporter assay confirmed that PPAR{gamma} was crucial for the downregulation of p16 mRNA transcription, and that the action was augmented by pioglitazone. Thus, pioglitazone exerted cell-cycle dependent promoting effect on preadipocyte proliferation, of which mechanisms include p16-downregulation through PPAR{gamma}.

  3. Use of pioglitazone in the treatment of diabetes: effect on cardiovascular risk.

    Science.gov (United States)

    Zou, Cong; Hu, Honglin

    2013-01-01

    Pioglitazone and other thiazolidinediones (TZDs) initially showed great promise as unique receptor-mediated oral therapy for type 2 diabetes, but a host of serious side effects, primarily cardiovascular, have limited their utility. It is crucial at this point to perform a risk- benefit analysis to determine what role pioglitazone should play in our current treatment of type 2 diabetes and where the future of this class of drugs is headed. This review provides a comprehensive overview of the present literature. Clinical data currently available indicate that pioglitazone is an effective and generally well-tolerated treatment option for use in patients with type 2 diabetes. Pioglitazone can still reduce adverse cardiovascular risk.

  4. Possible link of pioglitazone with bladder cancer in Japanese patients with type 2 diabetes.

    Science.gov (United States)

    Fujimoto, Kanta; Hamamoto, Yoshiyuki; Honjo, Sachiko; Kawasaki, Yukiko; Mori, Kanako; Tatsuoka, Hisato; Matsuoka, Atsuko; Wada, Yoshiharu; Ikeda, Hiroki; Fujikawa, Jun; Koshiyama, Hiroyuki

    2013-02-01

    We retrospectively examined the frequency of bladder cancer in Japanese patients with type 2 diabetes in relation to use of pioglitazone. Among a total of 663 patients identified to be taking pioglitazone, 9 had bladder cancer (1.36%). Overall the hazard ratio of 1.75 [95% CI: 0.89-3.45] for pioglitazone for bladder cancer was not significant. However the prevalence of bladder cancer was 2.10% in patients taking pioglitazone for less than 24 months which was significant increased (HR 2.73 [95% CI: 1.11-6.72]).

  5. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... Acute Pancreatitis and Pregnancy test 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 ...

  6. Pancreatic fistula may be an important complication following spleen-preserving radical gastrectomy with dissection of No.10 and No.11 lymph nodes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jun; ZHANG Zhong-tao; WANG Yu; WANG Kang-li

    2010-01-01

    @@ In recent years, spleen-preserving radical gastrectomy with dissection of No.10 and No.11 lymph nodes has been gradually accepted because of an improved understanding of immune function of the spleen in the perioperative period and for prognosis of gastric cancer.

  7. Linagliptin and pioglitazone combination therapy versus monotherapy with linagliptin or pioglitazone: A randomised, double-blind, parallel-group, multinational clinical trial.

    Science.gov (United States)

    Nauck, Michael Albrecht; di Domenico, Maximiliano; Patel, Sanjay; Kobe, Maureen; Toorawa, Robert; Woerle, Hans-Juergen

    2016-07-01

    Linagliptin plus pioglitazone single-pill combinations were evaluated. Patients (n = 936) with insufficient glycaemic control, despite lifestyle interventions, were randomised for 30 weeks to either monotherapy with linagliptin 5 mg; pioglitazone 15, 30 or 45 mg; or single-pill combination with linagliptin 5 mg plus pioglitazone 15, 30 or 45 mg. An extension (⩽54 weeks) planned to evaluate linagliptin plus pioglitazone 30 or 45 mg single-pill combinations was not completed due to a protocol amendment. Adjusted mean (95% confidence interval) differences in HbA1c change from baseline at week 30 for linagliptin plus pioglitazone 15, 30 and 45 mg were -0.17% (-0.41, 0.07), -0.37% (-0.60, -0.14) and -0.41% (-0.64, -0.18) versus pioglitazone monotherapies, respectively, and -0.44% (-0.67, -0.20), -0.68% (-0.91, -0.44) and -0.89% (-1.12, -0.66) versus linagliptin monotherapy, respectively. Single-pill combinations were generally well tolerated. Hypoglycaemia frequency was ⩽1.5% per group. Linagliptin plus pioglitazone combinations were efficacious, with safety profiles comparable to the individual monotherapies.

  8. Complicated Pancreatitis

    NARCIS (Netherlands)

    Bakker, O.J.

    2015-01-01

    Research questions addressed in this thesis: What is the accuracy of serum blood urea nitrogen as early predictor of complicated pancreatitis? ; What is difference in clinical outcome between patients with pancreatic parenchymal necrosis and patients with extrapancreatic necrosis without necrosis

  9. Chronic pancreatitis

    Science.gov (United States)

    ... or oily stools Pale or clay-colored stools Exams and Tests Tests to diagnose pancreatitis include: Fecal ... in the diet, or as extra supplements Limiting caffeine The health care provider may prescribe pancreatic enzymes. ...

  10. Complicated Pancreatitis

    NARCIS (Netherlands)

    Bakker, O.J.

    2015-01-01

    Research questions addressed in this thesis: What is the accuracy of serum blood urea nitrogen as early predictor of complicated pancreatitis? ; What is difference in clinical outcome between patients with pancreatic parenchymal necrosis and patients with extrapancreatic necrosis without necrosis

  11. Pancreatic abscess

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000270.htm Pancreatic abscess To use the sharing features on this page, please enable JavaScript. A pancreatic abscess is an area filled with pus within the ...

  12. Childhood pancreatitis.

    Science.gov (United States)

    Uretsky, G; Goldschmiedt, M; James, K

    1999-05-01

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

  13. Chronic pancreatitis

    OpenAIRE

    Kocher, Hemant M.; Froeling, Fieke EM

    2008-01-01

    Chronic pancreatitis is characterised by long-standing inflammation of the pancreas owing to a wide variety of causes, including recurrent acute attacks of pancreatitis. Chronic pancreatitis affects 3–9 people in 100,000; 70% of cases are alcohol-induced.

  14. Chronic pancreatitis

    OpenAIRE

    Kocher, Hemant M.; Kadaba, Raghu

    2011-01-01

    Chronic pancreatitis is characterised by long-standing inflammation of the pancreas due to a wide variety of causes, including recurrent acute attacks of pancreatitis. Chronic pancreatitis affects between 3 and 9 people in 100,000; 70% of cases are alcohol-induced.

  15. Adult Pancreatic Hemangioma: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Gerhard S. Mundinger

    2009-01-01

    Full Text Available We report an adult pancreatic hemangioma diagnosed on pathological specimen review following pylorus preserving pancreaticoduodenectomy for a symptomatic cystic mass in the head of the pancreas. Eight cases of adult pancreatic hemangioma have been reported in literature since 1939. Presenting symptoms, radiographic diagnosis, pathologic characteristics, and treatment of adult pancreatic hemagiomas are discussed following review of all published cases.

  16. Effects and Potential Mechanisms of Pioglitazone on Lipid Metabolism in Obese Diabetic KKAy Mice

    Directory of Open Access Journals (Sweden)

    Jun Peng

    2014-01-01

    Full Text Available This study aimed to analyze the effects and potential mechanisms of pioglitazone on triglyceride and cholesterol metabolism in obese diabetic KKAy mice. Pioglitazone was orally administered to KKAy mice over 30 days. Compared to C57BL/6J mice, KKAy mice developed obvious insulin resistance, hepatic steatosis, and hyperlipidemia. Pioglitazone treatment resulted in deteriorated microvesicular steatosis and elevated hepatic triglyceride levels, though plasma triglyceride and free fatty acid levels were reduced by the treatment, compared to nontreated KKAy mice. Plasma alanine aminotransferase activities were also significantly increased. Additionally, pioglitazone increased plasma concentrations of total cholesterol, HDL-cholesterol, and LDL-cholesterol but decreased hepatic cholesterol. Gene expression profiling revealed that pioglitazone stimulated hepatic peroxisome proliferator-activated receptor gamma hyperactivity, and induced the upregulation of adipocyte-specific and lipogenesis-related genes but downregulated of genes involved in triglyceride lipolysis and fatty acid β-oxidation. Pioglitazone also regulated the genes expression of hepatic cholesterol uptake and excretion, such as low density lipoprotein receptor (LDL-R and scavenger receptor type-BI (SR-BI. These results suggested that pioglitazone could induce excessive hepatic triglyceride accumulation, thus aggravating liver steatosis and lesions in KKAy mice. Furthermore, pioglitazone may suppress the clearance of serum cholesterol from the liver predominantly through inhibition of LDL-R and SR-BI expression, thus increasing the plasma cholesterol.

  17. Effect of method of preparation on pioglitazone HCl-β-cyclodextrin inclusion complexes

    Directory of Open Access Journals (Sweden)

    Beloshe Shrikant

    2010-01-01

    Full Text Available Pioglitazone HCl is an antidiabetic agent with poor aqueous solubility. Inclusion complexes of pioglitazone HCl were prepared with β-cyclodextrin using various methods (physical mixing, kneading method, co-precipitation. The main aim of the present invention is to study the effect of the method of preparation on the dissolution profiles of pioglitazone HCl-β-Cyclodextrin inclusion complexes . The phase solubility profile of pioglitazone HCl with β-cyclodextrin was classified as AL-type and stability constant with 1:1 molar ratio was 115.45, calculated from the phase solubility diagram. Formation of the inclusion complex between pioglitazone HCl and β-cyclodextrin was confirmed by the Fourier Transform Infrared (FT-IR spectroscopy. The dissolution profile of inclusion complexes were determined and compared with those of pioglitazone HCl alone and its physical mixtures. The dissolution rate of the pioglitazone HCl-β-cyclodextrin inclusion complex prepared by the co-precipitation method was six times higher when compared with the pure drug. The method of complexation of pioglitazone HCl in β-CD increased the dissolution rate of the drug in the following order: Coppt > KM > PM >Drug.

  18. Pioglitazone has a dubious bladder cancer risk but an undoubted cardiovascular benefit.

    Science.gov (United States)

    Ryder, R E J

    2015-03-01

    On 8 April 2014, a US jury ordered Takeda and Eli Lilly to pay $9 bn in punitive damages after finding that they had concealed the cancer risks associated with pioglitazone. By contrast, on 28 August 2014, the long-awaited outcome of the 10-year Kaiser Permanente Northern California study was announced. That study was specifically designed to investigate whether patients exposed to pioglitazone were at an increased risk of bladder cancer and found no association; thus, at last, the controversial issue has been resolved. A review, in retrospect, of the story of the proposed link between pioglitazone and bladder cancer reveals flaws at every stage. In 2012, a BMJ editorial, in keeping with some other contemporary reports, stated 'it can confidently be assumed that pioglitazone increases the risk of bladder cancer'. Examination of the information which led to such a statement shows that: 1) the pre-clinical findings of bladder cancer in male rats is not indicative of human risk; 2) there is no association between bladder cancer and pioglitazone in randomized controlled trials, once cases that could not plausibly be related to treatment are removed; and 3) the observational studies that have suggested a link have over-extrapolated from the data: pioglitazone-treated patients had more risk factors for bladder cancer than those not treated with pioglitazone. Meanwhile careful study of randomized controlled trials shows evidence of cardiovascular benefit from pioglitazone in Type 2 diabetes, a condition which results, more than anything, in premature cardiovascular death and morbidity.

  19. Hereditary pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Richard M Charnley

    2003-01-01

    Hereditary pancreatitis is an autosomal dominant condition,which results in recurrent attacks of acute pancreatitis,progressing to chronic pancreatitis often at a young age.The majority of patients with hereditary pancreatitis expressone of two mutations (R122H or N29I) in the cationictrypsinogen gene (PRSS1 gene). It has been hypothesisedthat one of these mutations, the R122H mutation causespancreatitis by altering a trypsin recognition site sopreventing deactivation of trypsin within the pancreas andprolonging its action, resulting in autodigestion. Families withthese two mutations have been identified in many countriesand there are also other rarer mutations, which have alsobeen linked to hereditary pancreatitis.Patients with hereditary pancreatitis present in the sameway as those with sporadic pancreatitis but at an earlierage. It is common for patients to remain undiagnosed formany years, particularly ifthey present with non-specificsymptoms. Hereditary pancreatitis should always beconsidered in patients who present with recurrent pancreatitiswith a family history of pancreatic disease. If patients withthe 2 common mutations are compared, those with theR122H mutation are more likely to present at a younger ageand are more likely to require surgical intervention than thosewith N29I. Hereditary pancreatitis carries a 40 % lifetimerisk of pancreatic cancer with those patients aged between50 to 70 being most at risk in whom screening tests maybecome important.

  20. Pioglitazone promotes preadipocyte proliferation by downregulating p16(Ink4a).

    Science.gov (United States)

    Hasan, Arif U; Ohmori, Koji; Hashimoto, Takeshi; Kamitori, Kazuyo; Hirata, Yuko; Ishihara, Yasuhiro; Okamoto, Naoko; Noma, Takahisa; Kosaka, Hiroaki; Tokuda, Masaaki; Kohno, Masakazu

    2011-07-29

    Pioglitazone, a synthetic ligand of peroxisome proliferator-activated receptor (PPAR)γ, causes preadipocyte proliferation through a mechanism which still remains elusive. Here, to address the mechanism, we investigated the effects of PPARγ and pioglitazone on the kinetics of cyclin-dependent kinase inhibitors, especially with p16(Ink4a) (p16) centered, by employing 3T3-L1 preadipocytes. Pioglitazone promoted preadipocyte proliferation by increasing S and G(2)/M cell-cycle entry, which was accompanied by decreased p16 mRNA expression. PPARγ overexpression along with the luciferase reporter assay confirmed that PPARγ was crucial for the downregulation of p16 mRNA transcription, and that the action was augmented by pioglitazone. Thus, pioglitazone exerted cell-cycle dependent promoting effect on preadipocyte proliferation, of which mechanisms include p16-downregulation through PPARγ. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Reduced serum dipeptidyl peptidase-IV after metformin and pioglitazone treatments.

    Science.gov (United States)

    Lenhard, James M; Croom, Dallas K; Minnick, Dana T

    2004-11-05

    Dipeptidyl peptidase-IV (DPP-IV) regulates metabolism by degrading incretins involved in nutritional regulation. Metformin and pioglitazone improve insulin sensitivity whereas glyburide promotes insulin secretion. Zucker diabetic rats were treated with these antidiabetic agents for 2 weeks and DPP-IV activity and expression were determined. Serum DPP-IV activity increased whereas tissue activity decreased as the rats aged. Treatment of rats with metformin, pioglitazone, and glyburide did not alter DPP-IV mRNA expression in liver or kidney. Metformin and pioglitazone significantly (PMetformin, pioglitazone, and glyburide had no effect on serum DPP-IV activity in vitro, indicating these are not competitive DPP-IV inhibitors. We propose the in vivo inhibitory effects observed with metformin and pioglitazone on serum DPP-IV activity results from reduced DPP-IV secretion.

  2. Autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Davorin Dajčman

    2007-05-01

    Full Text Available Background: Autoimmune pancreatitis is a recently described type of pancreatitis of presumed autoimmune etiology. Autoimmune pancreatitis is often misdiagnosed as pancreatic cancer difficult, since their clinical presentations are often similar. The concept of autoimmune pancreatitis was first published in 1961. Since then, autoimmune pancreatitis has often been treated not as an independent clinical entity but rather as a manifestation of systemic disease. The overall prevalence and incidence of the disease have yet to be determined, but three series have reported the prevalence as between 5 and 6 % of all patients with chronic pancreatitis. Patient vary widely in age, but most are older than 50 years. Patients with autoimmune pancreatitis usually complain of the painless jaundice, mild abdominal pain and weight loss. There is no laboratory hallmark of the disease, even if cholestatic profiles of liver dysfunction with only mild elevation of amylase and lipase levels have been reported.Conclusions: Proposed diagnostic criteria contains: (1 radiologic imaging, diffuse enlargement of the pancreas and diffusely irregular narrowing of the main pancreatic duct, (2 laboratory data, elevated levels of serum ã-globulin and/or IgG, specially IgG4, or the presence of autoantibodies and (3 histopathologic examination, fibrotic change with dense lymphoplasmacytic infiltration in the pancreas. For correct diagnosis of autoimmune pancreatitis, criterion 1 must be present with criterion 2 and/or 3. Autoimmune pancreatitis is frequently associated with rheumatoid arthritis, Sjogren’s syndrome, inflammatory bowel disease, tubulointersticial nephritis, primary sclerosing cholangitis and idiopathic retroperitoneal fibrosis. Pancreatic biopsy using an endoscopic ultrasound-guided fine needle aspiration biopsy is the most important diagnostic method today. Treatment with corticosteroids leads to the and resolution of pancreatic inflamation, obstruction and

  3. Surgical management of chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Stavros Gourgiotis; Stylianos Germanos; Marco Pericoli Ridolifni

    2007-01-01

    BACKGROUND:Treatment of chronic pancreatitis (CP) is a challenging condition for surgeons. During the last decades, increasing knowledge about pathophysiology of CP, improved results of major pancreatic resections, and integration of sophisticated diagnostic methods in clinical practice have resulted in signiifcant changes in surgery for CP. DATA SOURCES:To detail the indications for CP surgery, the surgical procedures, and outcome, a Pubmed database search was performed. The abstracts of searched articles about surgical management of CP were reviewed. The articles could be identiifed and further scrutinized. Further references were extracted by cross-referencing. RESULTS: Main indications of CP for surgery are intractable pain, suspicion of malignancy, and involvement of adjacent organs. The goal of surgical treatment is to improve the quality of life of patients. The surgical approach to CP should be individualized according to pancreatic anatomy, pain characteristics, baseline exocrine and endocrine function, and medical co-morbidity. The approach usually involves pancreatic duct drainage and resection including longitudinal pancreatojejunostomy, pancreatoduodenectomy (Whipple's procedure), pylorus-preserving pancreatoduodenectomy, distal pancreatectomy, total pancreatectomy, duodenum-preserving pancreatic head resection (Beger's procedure), and local resection of the pancreatic head with longitudinal pancreatojejunostomy (Frey's procedure). Non-pancreatic and endoscopic management of pain has also been advocated. CONCLUSIONS:Surgical procedures provide long-term pain relief, a good postoperative quality of life with preservation of endocrine and exocrine pancreatic function, and are associated with low early and late mortality and morbidity. In addition to available results from randomized controlled trials, new studies are needed to determine which procedure is the most effective for the management of patients with CP.

  4. Pancreatic Juice Culture in Acute Pancreatitis and Other Pancreatic Disorders

    Directory of Open Access Journals (Sweden)

    Masataka Kikuyama

    2016-09-01

    Full Text Available We retrospectively evaluated the results of pancreatic juice cultures of patients with acute pancreatitis and other pancreatic disorders. Methods Twenty patients who underwent pancreatic juice culture were studied. Nine had acute pancreatitis due to alcohol (n=5, idiopathic causes (n=2, drugs (n=1, or gallstones (n=1, and remaining 11 had other pancreatic disorders such as an intraductal papillary mucin-producing neoplasm (n=3 and main pancreatic duct dilatation with a stricture due to a tumorous lesion suspected of pancreatic cancer (n=7 or chronic pancreatitis (n=1 without symptoms. Nasopancreatic drainage tubes were placed for pancreatic duct drainage in acute pancreatitis and for pancreatic juice cytology in other disorders. Pancreatic juice was obtained through the drainage tube and cultured. Results Pancreatic juice cultures were positive in all patients with acute pancreatitis for Staphylococcus epidermidis, Streptococcus species, and others. Six among 11 patients (54.5% with other disorders showed positive results for Escherichia coli, Streptococcus salivarius, and others. The rate of positive pancreatic juice cultures was significantly higher in acute pancreatitis (p=0.038. Seven of the 9 patients with acute pancreatitis were classified as having severe acute pancreatitis, and all survived treatment. Conclusions Pancreatic juice culture was highly positive in acute pancreatitis. Further study is needed to confirm the relationship between orally indigenous bacteria identified in the pancreatic juice and acute pancreatitis.

  5. Chronic Pancreatitis in Children

    Science.gov (United States)

    ... Information > Children/Pediatric > Chronic Pancreatitis in Children test Chronic Pancreatitis in Children What symptoms would my child ... pancreatitis will develop diabetes in adolescence. Who gets chronic pancreatitis? Those at risk for chronic pancreatitis are ...

  6. Effects of pioglitazone and metformin on vascular endothelial function in patients with type 2 diabetes treated with sulfonylureas.

    Science.gov (United States)

    Naka, Katerina K; Papathanassiou, Katerina; Bechlioulis, Aris; Pappas, Konstantinos; Kazakos, Nikolaos; Kanioglou, Chryssanthi; Kostoula, Aggeliki; Vezyraki, Patra; Makriyiannis, Demetrios; Tsatsoulis, Agathocles; Michalis, Lampros K

    2012-01-01

    Pioglitazone and metformin are insulin sensitisers used for the treatment of T2DM. The effects of pioglitazone and metformin on endothelial function, assessed by FMD, in T2DM patients treated with sulfonylureas were compared. Patients were randomised to receive pioglitazone (n = 15) 30 mg once daily or metformin (n = 16) 850 mg twice daily for six months. Pioglitazone significantly decreased fasting insulin, HbA(1C) and HOMA-IR (p pioglitazone, compared with metformin, did not reach significance (p = 0.11). Treatment-induced changes in FMD were not associated with the effects of the two insulin sensitisers on glycaemic control or insulin resistance. The beneficial effects of pioglitazone and metformin on endothelial function in T2DM patients did not differ greatly. Larger studies are needed to explore whether a potentially greater benefit with pioglitazone may exist.

  7. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    Science.gov (United States)

    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)

  8. Obesity, pancreatitis, and pancreatic cancer.

    Science.gov (United States)

    Gumbs, Andrew A

    2008-09-01

    The only universally accepted risk factors for the development of pancreatic cancer are a positive family history or a history of smoking. Although the contribution of pancreatitis to pancreatic carcinogenesis has been debated for decades in the epidemiology literature, the actual mechanism is still unclear. With the rising epidemic of obesity, scientists have begun to focus on the contribution of chronic inflammatory state of morbidly obese patients in an effort to better understand the contribution of inflammation to the comorbidities of obesity. Notably, population studies are beginning to show that one of the most serious potential comorbidities of obesity is an increased lifetime risk of developing cancer. In this article, the current literature that exists supporting this Chronic Inflammatory Hypothesis as it pertains to obesity and pancreatic carcinogenesis is reviewed. To date, studies have focused on interleukin-6, a cytokine known to play a role in obesity, chronic pancreatitis and pancreatic cancer. The anti-inflammatory adipocytokine, adiponectin, has also shown promise as a key player in this mechanism and has recently been found to be more specific than standard tumor markers in differentiating pancreatic cancer from chronic pancreatitis. If the pathogenesis of pancreatic cancer is related to hormone levels associated with obesity, such as adipocytokines, and cytokines associated with chronic inflammation, this could potentially lead to the development of new pancreatic cancer tumor markers and ultimately new therapies and methods of prevention.

  9. Effects of PPARg agonist pioglitazone on rat hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Guang-Jin Yuan; Ming-Liang Zhang; Zuo-Jiong Gong

    2004-01-01

    AIM: To investigate effects of pioglitazone on rat hepatic fibrosis and to explore its mechanism.METHODS: Rat hepatic fibrosis was induced by carbon tet:achloride (CCl4). Forty Sprague-Dawley rats were divided randomly into 4 groups: control, model, and two treatment (PⅠ, PⅡ) groups. Except for rats in control group, all rats were given subcutaneous injection of 400 mL/L CCl4, twice a wk for 8 wk. Rats in PⅠ and PⅡ groups were also treated with pioglitazone of 3 mg/kg, daily via gastrogavage beginning on the 1st day and at the end of the 2nd week,administration of CCl4 respectively. Liver functions (ALT,AST), serum fibrotic markers (HA, LN, PCⅢ) and hepatic hydroxyproline (HP) concentration were determined respectively. Histochemical staining of formalin-fixed liver sections with HE, Masson-Trichrome, and immunohistochemical staining for α-smooth muscle actin (α-SMA) were performed.Modified Knodell and Chevallier semi-quantitative scoring system (SSS) was used to evaluate necroinflammatory activity and fibrosis degree.RESULTS: Compared with model group, pioglitazone significantly reduced the serum levels of ALT, AST, HA, LN and PCⅢ (P<0.05 or <0.01). The HP concentrations in PⅠ (210.90±24.07 μg/g), and PⅡ (257.36±30.55 μg/g) groups were also lower than those in model group (317.80±36.44 μg/g) (P<0.01). Histologic examination showed that PⅠ and PⅡ groups had milder hepatocellular degeneration, necrosis and infiltration of inflammatory cells, and thinner or less fibrotic septa than did model group. The scores for necroinflammation in PⅠ (2.80±1.03), and PⅡ (3.00±1.05) groups were significantly reduced as compared with model group (4.88±2.30) (P<0.05 or <0.01); the fibrosis scores in PⅠ (3.40±1.65), and PⅡ (4.60±1.35) groups were also markedly lower than those in model group (7.00±3.21)(P<0.05 or <0.01). Immunohistochemical staining showed that expression of α-SMA in PⅠ and PⅡ groups was ameliorated

  10. Pioglitazone attenuates tactile allodynia and thermal hyperalgesia in mice subjected to peripheral nerve injury.

    Science.gov (United States)

    Maeda, Takehiko; Kiguchi, Norikazu; Kobayashi, Yuka; Ozaki, Masanobu; Kishioka, Shiroh

    2008-11-01

    To clarify the role of peroxisome proliferator activated receptor gamma (PPARgamma) in neuropathic pain, we examined the effect of pioglitazone, a PPARgamma agonist, on tactile allodynia and thermal hyperalgesia in a neuropathic pain model. Mice were subjected to partial sciatic nerve ligation (PSL) and given pioglitazone (1 - 25 mg/kg, p.o.) once daily. PPARgamma was distributed in the neurons of the dorsal root ganglion and the dorsal horn of the spinal cord and in the adipocytes at the epineurium of the sciatic nerve in naive mice. PSL elicited tactile allodynia and thermal hyperalgesia for two weeks. Administration of pioglitazone for the first week after PSL attenuated thermal hyperalgesia and tactile allodynia, which was dose-dependent and blocked by GW9662 (2 mg/kg, i.p.), a PPARgamma antagonist. Administration of pioglitazone for the second week also relieved tactile allodynia, but administration one week before PSL had no effect. A single administration of pioglitazone to mice on day 7 of PSL did not alter tactile allodynia and thermal hyperalgesia. PSL-induced upregulation of tumor necrosis factor-alpha and interleukin-6, which are essential for neuropathic pain, was suppressed by pioglitazone for the first week. This suggests that pioglitazone alleviates neuropathic pain through attenuation of proinflammatory cytokine upregulation by PPARgamma stimulation.

  11. Pioglitazone does not affect vascular or inflammatory responses after endotoxemia in humans.

    Science.gov (United States)

    Schaller, G; Kolodjaschna, J; Pleiner, J; Mittermayer, F; Kapiotis, S; Schmetterer, L; Wolzt, M

    2008-08-01

    PPARgamma agonists have been proposed to exert more than metabolic benefits, particularly by anti-inflammatory mechanisms. We hypothesized that pioglitazone might modulate inflammatory and vascular responses to lipopolysaccharide (LPS). In a placebo-controlled parallel-group study in 18 healthy male subjects, the E. coli endotoxin model of inflammation (20 IU/kg i. v.) was employed to test the effect of 60 mg pioglitazone over nine days on inflammatory cytokines. Macrovascular function and microvascular blood flow were assessed by brachial artery ultrasound and retinal blood flow parameters, respectively. Pioglitazone increased brachial artery diameter by 5.6% but had no effect on other outcome parameters under resting conditions. LPS increased cytokine levels to peak concentrations of 91.3+/-22.5 ng/ml (IL-6), 261.4+/-60.0 ng/ml (TNFalpha), and 524.5+/-15.3 ng/ml (VCAM-1). The endotoxin caused microvascular vasodilation and increased retinal white blood cell flux, while baseline brachial artery diameter remained unchanged. Pioglitazone had no effect on inflammatory cytokine or adhesion molecule release but mitigated LPS-induced hypotension (p<0.05). Neither brachial artery function nor microvascular blood flow was altered by pioglitazone. In conclusion, acute immune reactions to LPS are not affected by pioglitazone, which exerts subtle vascular effects alone and during endotoxemia. The anti-inflammatory properties of short-term pioglitazone to endotoxins in healthy subjects are therefore limited.

  12. Direct inhibitory effects of pioglitazone on hepatic fetuin-A expression.

    Directory of Open Access Journals (Sweden)

    Akinobu Ochi

    Full Text Available Fetuin-A, a circulating glycoprotein synthesized in the liver, is involved in insulin resistance and type 2 diabetes. However, regulation of fetuin-A synthesis has remained obscure. We previously reported that pioglitazone treatment significantly reduced serum fetuin-A levels in patients with type 2 diabetes. To clarify whether pioglitazone can directory inhibit hepatic fetuin-A synthesis, we investigated the effects of pioglitazone on fetuin-A expression both in vitro and in vivo. Pioglitazone treatment suppressed mRNA and protein expression of fetuin-A in Fao hepatoma cells. Interestingly, rosiglitazone but not metformin, also inhibited fetuin-A expression. In addition, GW 9662, an inhibitor of peroxisome proliferator-activated receptor (PPAR γ, reversed pioglitazone-induced suppression of fetuin-A, suggesting that thiazolidinedione derivatives may have common characteristics with regard to fetuin-A suppression, possibly through PPARγactivation. Finally, oral administration of pioglitazone to mice for 8 weeks resulted in suppression of hepatic fetuin-A mRNA. These findings suggest that pioglitazone may partially ameliorate insulin resistance through its direct inhibitory effects on fetuin-A expression in the liver.

  13. Treatment with pioglitazone is associated with decreased preprandial ghrelin levels: a randomized clinical trial.

    Science.gov (United States)

    Taslimi, Shervin; Esteghamati, Alireza; Rashidi, Armin; Tavakkoli, Hosein Moin; Nakhjavani, Manouchehr; Kebriaee-Zadeh, Abbas

    2013-02-01

    The effects of metformin and pioglitazone on ghrelin, a physiologic regulator of appetite and food intake, have not been clearly established. In a randomized clinical trial, we randomly assigned 60 type 2 diabetic patients to either metformin (Group A; n=30) or pioglitazone (Group B; n=30) treatment groups. The groups were similar in their baseline characteristics. A standard fasting 75 g oral glucose tolerance test was performed at time zero before starting metformin or pioglitazone, and 3 months later. After 3 months of treatment, pioglitazone, but not metformin, was significantly associated with weight gain. Both groups experienced a significant reduction in fasting plasma glucose (ppioglitazone group had a significant reduction in preprandial ghrelin levels after treatment (ppioglitazone on ghrelin was independent of changes in body weight, body mass index, glucose control, insulin resistance, and plasma insulin. In conclusion, treatment with pioglitazone is associated with a decrease in preprandial ghrelin levels and therefore, the weight gain and increased food intake related to pioglitazone use cannot be explained by its effects on ghrelin. The effect of pioglitazone on ghrelin is independent of changes in body weight, body mass index, plasma insulin, insulin resistance, or glucose control.

  14. Direct inhibitory effects of pioglitazone on hepatic fetuin-A expression.

    Science.gov (United States)

    Ochi, Akinobu; Mori, Katsuhito; Emoto, Masanori; Nakatani, Shinya; Morioka, Tomoaki; Motoyama, Koka; Fukumoto, Shinya; Imanishi, Yasuo; Koyama, Hidenori; Ishimura, Eiji; Inaba, Masaaki

    2014-01-01

    Fetuin-A, a circulating glycoprotein synthesized in the liver, is involved in insulin resistance and type 2 diabetes. However, regulation of fetuin-A synthesis has remained obscure. We previously reported that pioglitazone treatment significantly reduced serum fetuin-A levels in patients with type 2 diabetes. To clarify whether pioglitazone can directory inhibit hepatic fetuin-A synthesis, we investigated the effects of pioglitazone on fetuin-A expression both in vitro and in vivo. Pioglitazone treatment suppressed mRNA and protein expression of fetuin-A in Fao hepatoma cells. Interestingly, rosiglitazone but not metformin, also inhibited fetuin-A expression. In addition, GW 9662, an inhibitor of peroxisome proliferator-activated receptor (PPAR) γ, reversed pioglitazone-induced suppression of fetuin-A, suggesting that thiazolidinedione derivatives may have common characteristics with regard to fetuin-A suppression, possibly through PPARγactivation. Finally, oral administration of pioglitazone to mice for 8 weeks resulted in suppression of hepatic fetuin-A mRNA. These findings suggest that pioglitazone may partially ameliorate insulin resistance through its direct inhibitory effects on fetuin-A expression in the liver.

  15. Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity.

    Science.gov (United States)

    Genc, Gurkan; Kilinc, Veli; Bedir, Abdulkerim; Ozkaya, Ozan

    2014-08-01

    Cisplatin is a chemotherapeutic agent, which is used in the treatment of various solid organ cancers, and its main dose limiting side effect of cisplatin is nephrotoxicity. The aim of this study is to investigate the role of pioglitazone and creatine on cisplatin nephrotoxicity in vitro. Real-time cell analyzer system (RTCA) was used for real-time and time-dependent analysis of the cellular response of HK-2 cells following incubation with cisplatin and combination with creatine or pioglitazone hydrochloride. First, half-maximal inhibitory concentrations (IC50) of cisplatin, creatine and pioglitazone were calculated by RTCA system. Afterwards creatine and pioglitazone was administered with serial dilutions under RTCA system. IC50 dose for cisplatin was 7.69 M × 10(-5) at 24th hour and 3.93 M × 10(-6) at 48th hour. IC50 dose for pioglitazone was 1.61 M × 10(-3) at 24th hour and 2.85 M × 10(-4) at 48th hour. Although cells were treated the dose of 40,225 mM creatine, IC50 dose could not been reached. Neither pioglitazone nor creatine had additional protective effect in any dose. Consequently, beneficial effect of creatine and pioglitazone on cisplatin-induced cell death could not be found. Further studies and clinical trials are needed to evaluate the effect of different doses of these drugs in cisplatin-induced nephrotoxicity.

  16. Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo.

    Science.gov (United States)

    Bogacka, Iwona; Xie, Hui; Bray, George A; Smith, Steven R

    2005-05-01

    Thiazolidenediones such as pioglitazone improve insulin sensitivity in diabetic patients by several mechanisms, including increased uptake and metabolism of free fatty acids in adipose tissue. The purpose of the present study was to determine the effect of pioglitazone on mitochondrial biogenesis and expression of genes involved in fatty acid oxidation in subcutaneous fat. Patients with type 2 diabetes were randomly divided into two groups and treated with placebo or pioglitazone (45 mg/day) for 12 weeks. Mitochondrial DNA copy number and expression of genes involved in mitochondrial biogenesis were quantified by real-time PCR. Pioglitazone treatment significantly increased mitochondrial copy number and expression of factors involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1alpha and mitochondrial transcription factor A. Treatment with pioglitazone stimulated the expression of genes in the fatty acid oxidation pathway, including carnitine palmitoyltransferase-1, malonyl-CoA decarboxylase, and medium-chain acyl-CoA dehydrogenase. The expression of PPAR-alpha, a transcriptional regulator of genes encoding mitochondrial enzymes involved in fatty acid oxidation, was higher after pioglitazone treatment. Finally, the increased mitochondrial copy number and the higher expression of genes involved in fatty acid oxidation in human adipocytes may contribute to the hypolipidemic effects of pioglitazone.

  17. The effect of pioglitazone on aldosterone and cortisol production in HAC15 human adrenocortical carcinoma cells.

    Science.gov (United States)

    Pan, Zhi-qiang; Xie, Ding; Choudhary, Vivek; Seremwe, Mutsa; Tsai, Ying-Ying; Olala, Lawrence; Chen, Xunsheng; Bollag, Wendy B

    2014-08-25

    Pioglitazone belongs to the class of drugs called thiazolidinediones (TZDs), which are widely used as insulin sensitizers in the treatment of diabetes. A major side effect of TZDs is fluid retention. The steroid hormone aldosterone also promotes sodium and fluid retention; however, the effect of pioglitazone on aldosterone production is controversial. We analyzed the effect of pioglitazone alone and in combination with angiotensin II (AngII) on the late rate-limiting step of adrenocortical steroidogenesis in human adrenocortical carcinoma HAC15 cells. Treatment with pioglitazone for 24 h significantly increased the expression of CYP11B2 and enhanced AngII-induced CYP11B2 expression. Despite the observed changes in mRNA levels, pioglitazone significantly inhibited AngII-induced aldosterone production and CYP11B2 protein levels. On the other hand, pioglitazone stimulated the expression of the unfolded protein response (UPR) marker DDIT3, with this effect occurring at early times and inhibitable by the PPARγ antagonist GW9962. The levels of DDIT3 (CHOP) and phospho-eIF2α (Ser51), a UPR-induced event that inhibits protein translation, were also increased. Thus, pioglitazone promotes CYP11B2 expression but nevertheless inhibits aldosterone production in AngII-treated HAC15 cells, likely by blocking global protein translation initiation through DDIT3 and phospho-eIF2α. In contrast, pioglitazone promoted AngII-induced CYP11B1 expression and cortisol production. Since cortisol enhances lipolysis, this result suggests the possibility that PPARs, activated by products of fatty acid oxidation, stimulate cortisol secretion to promote utilization of fatty acids during fasting. In turn, the ability of pioglitazone to stimulate cortisol production could potentially underlie the effects of this drug on fluid retention.

  18. Pioglitazone and the risk of bladder cancer: An Indian retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Sunil Gupta

    2015-01-01

    Full Text Available Aim: To determine whether pioglitazone is associated with an increased risk of bladder cancer among Indian type 2 diabetic patients. Methods: A retrospective data analysis of 2222 type 2 diabetic patients was conducted. The study subjects were divided into two equal groups: 1111 pioglitazone users and 1111 pioglitazone non-users. The safety of pioglitazone therapy was analyzed in terms of occurrence of bladder and other types of cancers along with its efficacy in terms of glycemic control. Parameters for assessing safety were duration of disease, duration of usage and total dose of pioglitazone consumed across age groups, glycemic control, obesity and family history of any cancer. Bladder cancer prevalence was analyzed on the basis of urinary cytology, urine routine and microscopy, hematuria, urinary nuclear matrix protein 22 analysis and ultrasonography. Results: Of the 2222 cases analysed, there was no evidence of bladder cancer in any of the studied groups, (p=not significant which was also evident among 1111 patients on Pioglitazone therapy with a cumulative dose consumption of 2737 mg to 1,31,400 mg. On subgroup analysis, there was no evidence of bladder cancer amongst patients with age >60 years, duration of diabetes > 10 years and uncontrolled diabetics (HbA1c >8% with cumulative pioglitazone consumption of >28,000 mg. A significant number of patients achieved good glycemic control (HbA1c <7.5% with pioglitazone therapy. Conclusion: Pioglitazone therapy was not associated with occurrence of bladder cancer among Indian type 2 diabetic patients and demonstrated good glycemic control.

  19. Prevention and treatment of postoperative complications of duodenum preserving pancreatic head resection%保留十二指肠胰头切除术后并发症的防治体会

    Institute of Scientific and Technical Information of China (English)

    朱世凯; 吴河水; 周玉; 熊炯圻; 赵刚; 王春友

    2009-01-01

    Objective To investigate the approach for prevention and treatment of postoperative complications of the duodenum-preserving pancreatic head resection (DPPHR). Method The clinical data of 56 patients receiving DPPHR in our hospital from 2003 to 2008 were retrospectively analyzed. Results Thirteen (23.3%) of the 56 patients had complications after DPPHR. The complications were pancreatic fistula in 7 cases (12.5%), duodenal fistula in 2 (5.4%) and biliary fistula in 1 (2.8%) and they were healed by supportive treatment and unobstructed drainage. Three cases (2.2%) of retroperitoneal infection were treated by putting drainage tube under ultrasonic guidance, 1 case (2.8%) with abdominal hemorrhage was disclosed to rupture and bleed in the branch of gastro-duodenal artery by selective celiac arteriography on emergency, and then treated with embolism with gelatin sponge and stainless steel. Conclusion The main complications after DPPHR are pancreatic fistula, duodenal fistula, biliary fistula, abdominal infection and hemorrhage. Meticulous operative technique, strict prehension of operation indications and complete reservation of blood supply of duo-denum are the key points to reduce postoperative complications and morbidity and increase operative a-chievement ratio after DPPHR. Meanwhile, correct methods should be used upon finding the compli-cations.%目的 探讨保留十二指肠胰头切除术后并发症的防治措施.方法 回顾性分析2003-2008年期间武汉协和医院胰腺中心行保留十二指肠胰头切除术56例病人的临床诊疗经过.结果 术后发生并发症13例(23.2%),包括胰瘘7例(12.5%),十二指肠瘘2例(5.4%);胆瘘1例(2.8%);腹膜后积液和感染2例(5.4%);腹腔大出血1例(2.8%).消化道瘘经支持治疗和维持通畅引流等治疗而痊愈,腹膜后积液和感染病人在B超引导下置管引流治愈,腹腔大出血者急诊选择性腹腔动脉造影显示胃十二指肠动脉分支破裂出血,经明胶海绵

  20. Pioglitazone Randomised Italian Study on Metabolic Syndrome (PRISMA): effect of pioglitazone with metformin on HDL-C levels in Type 2 diabetic patients.

    Science.gov (United States)

    Genovese, S; Passaro, A; Brunetti, P; Comaschi, M; Cucinotta, D; Egan, C G; Chinea, B; Bravi, F; Di Pietro, C

    2013-09-01

    Previous evidence indicates that pioglitazone may improve dyslipidemia in patients with Type 2 diabetes mellitus (T2DM). The primary objective of this study was to evaluate the effect of either pioglitazone or placebo with metformin on levels of serum HDL cholesterol (HDL-C) in patients with T2DM. A secondary objective evaluated changes in metabolic syndrome (MS)-specific parameters. This multicenter, double-blind, randomized study was performed in patients with T2DM treated with metformin and hemoglobin A1c (HbA1c) levels between 6-8%, central obesity and reduced HDL-C. MS was evaluated from global changes in parameter values and expressed as a single factorial score following multivariate analysis of each parameter. 213 patients (110 in the pioglitazone group and 103 in the placebo group) were available for intention-to-treat analysis. Pioglitazone-treated patients showed a significant increase in HDL-C compared to placebo group (6.3 mg/dl vs 3.0 mg/dl; pHDL-C and the reduction of insulin resistance and atherogenic LDL subfractions), support findings from the PROactive trial, where pioglitazone showed pleiotropic effects and reduced death, fatal myocardial infarction (MI) and non-fatal MI in T2DM patients with MS. Furthermore, medication used in this study showed good tolerability.

  1. Pioglitazone treatment increases spontaneous growth hormone (GH) secretion and stimulated GH levels in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Støving, René Klinkby; Hagen, Claus

    2005-01-01

    and improved insulin sensitivity during pioglitazone treatment may affect GH secretion. OBJECTIVE: The objective of the study was to investigate the effect of pioglitazone on GH levels in PCOS. DESIGN: Thirty insulin-resistant PCOS patients were randomized to either 16 wk pioglitazone (30 mg/d) or placebo...... treatment. Before and after intervention, levels of fasting insulin, GH, total IGF-I, free IGF-I, IGF binding protein-1, IGF-II, free fatty acids, testosterone, and SHBG were measured. Patients underwent whole-body dual x-ray absorptiometry scans, pyridostigmine-GHRH tests, and 24-h 20-min integrated blood...... sampling for measurement of GH. RESULTS: Peak GH and area under the curve for GH in pyridostigmine-GHRH tests and 24-h mean GH concentrations and pulsatile GH secretion significantly increased after pioglitazone treatment. No significant changes were observed in GH pulse frequency, pulse duration...

  2. [Autoimmune pancreatitis].

    Science.gov (United States)

    Beyer, G; Menzel, J; Krüger, P-C; Ribback, S; Lerch, M M; Mayerle, J

    2013-11-01

    Autoimmune pancreatitis is a relatively rare form of chronic pancreatitis which is characterized by a lymphoplasmatic infiltrate with a storiform fibrosis and often goes along with painless jaundice and discrete discomfort of the upper abdomen. Clinically we distinguish between two subtypes, which differ in terms of their histology, clinical picture and prognosis. Type 1 autoimmune pancreatitis is the pancreatic manifestation of the IgG4-associated syndrome which also involves other organs. About one third of the patients can only be diagnosed after either histological prove or a successful steroid trail. Type 2 is IgG4-negative with the histological picture of an idiopathic duct centric pancreatitis and is to higher degree associated with inflammatory bowel disease. A definitive diagnosis can only be made using biopsy. Usually both forms show response to steroid treatment, but in type 1 up to 50 % of the patients might develop a relapse. The biggest challenge and most important differential diagnosis remains the discrimination of AIP from pancreatic cancer, because also AIP can cause mass of the pancreatic head, lymphadenopathy and ductal obstruction. This article summarizes recent advances on epidemiology, clinical presentation, diagnostic strategy, therapy and differential diagnosis in this relatively unknown disease.

  3. Autoimmune pancreatitis associated with a large pancreatic pseudocyst

    Institute of Scientific and Technical Information of China (English)

    Thilo Welsch; J(o)rg Kleeff; Irene Esposito; Markus W Büchler; Helmut Friess

    2006-01-01

    Pancreatic cystic lesions comprise various entities with different histopathological characteristics and their differential diagnosis is often a challenge for clinicians.Autoimmune pancreatitis (ATP) is usually not considered in the differential diagnosis of cystic lesions, but often mimics the morphological aspects of pancreatic neoplasm. We report the case of a 64-year-old male patient with a cystic pancreatic head lesion (diameter 5 cm) and stenosis of the distal bile duct requiring repeated stentlng. Because of the clinical presentation together with moderate elevation of serum CA19-9 and massive elevation of cyst fluid CA19-9 (122.695 U/L; normal range: <37.0 U/L), the patient underwent explorative laparotomy and pylorus preserving partial pancreaticoduodenectomy.Histology revealed surprisingly ATP with an inflammatory pseudocyst. Tn conclusion, cyst fluid analysis of tumor markers and cyst fluid cytology lack high accuracy to clearly differentiate cystic pancreatic lesions. Although ATP is rarely associated with pseudocysts, the disease has to be considered in the differential diagnosis of cystic pancreatic lesions. Early examination of serum IgG,IgG4 and auto-antibodies might save these patients from unnecessary endoscopical and surgical procedures.

  4. Pioglitazone (Actos) and bladder cancer: Legal system triumphs over the evidence.

    Science.gov (United States)

    Davidson, Mayer B

    2016-08-01

    In preclinical studies, pioglitazone was associated with bladder cancer in male rats (but not in female rats, mice dogs or monkeys). Because of this association, the Federal Drug Administration requested a large 10year epidemiological study to evaluate whether there was an association between bladder cancer and exposure to pioglitazone in patients. A 5-year interim report published in 2011 showed no significant association between ever vs never exposure to the drug but a significant association in patients exposed to pioglitazone for >2years. Importantly, the final 10year report did not confirm the 5year interim report finding no association between bladder cancer and pioglitazone, even after >4years of exposure to the drug. However, as would be expected, following the 5-year interim report, many epidemiological studies were carried out and civil litigation lawsuits began to be filed. Of the 23 epidemiological studies that have been published to date, 18 showed no association between bladder cancer and pioglitazone (5 with a combination of rosiglitazone and pioglitazone). Of the five that did show a significant association with pioglitazone, three could not be confirmed in the same population and in one of them there were significantly more risk factors for bladder cancer in the patients exposed to pioglitazone. In the fourth one, a significant association became non-significant when patients >79years were included. In the fifth one, detection bias was a major flaw. Currently, >11,000 legal cases have been filed, many of which claim emotional distress due to the fear of bladder cancer. To limit their legal costs, the pharmaceutical company has established a 2.4 billion dollar settlement pool. So much for evidence-based medicine.

  5. Role of autophagy in development and progression of acute pancreatitis

    Directory of Open Access Journals (Sweden)

    YANG Shuli

    2014-08-01

    Full Text Available Acute pancreatitis is considered an autodigestive disorder in which inappropriate activation of trypsinogen to trypsin within pancreatic acinar cells leads to the development of pancreatitis. Autophagy is an evolutionarily preserved degradation process of cytoplasmic cellular constituents, and it is one of the early pathological processes in acute pancreatitis. Autophagic flux is impaired in acute pancreatitis, which mediates the key pathologic responses of this disease. Impaired autophagy, dysfunction of lysosomes, and dysregulation of autophagy suggest a disorder of the endolysosomal pathway in acute pancreatitis. The role of autophagy in acute pancreatitis is discussed from the aspects of autophagic process, autophagy and activation of trypsinogen, impaired autophagy and acute pancreatitis, and defective autophagy promoting inflammation.

  6. Long-term pioglitazone therapy improves arterial stiffness in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Harashima, Keiichiro; Hayashi, Junichi; Miwa, Takashi; Tsunoda, Tooru

    2009-06-01

    Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, not only improves insulin resistance and glycemic control, but may also have additional beneficial vascular effects in patients with type 2 diabetes mellitus. We investigated whether pioglitazone had an influence on arterial stiffness, which is an independent predictor of cardiovascular events, in 204 patients with type 2 diabetes mellitus. A prospective, nonrandomized, open-label trial was performed that involved 41 patients treated with pioglitazone, 46 patients receiving sulfonylureas, 67 patients on insulin, and 50 patients on diet/exercise only. The follow-up period was 56 +/- 3 months. Arterial stiffness was evaluated by using the arterial stiffness index (ASI), which was based on analysis of the pulse wave amplitude pattern obtained during automated blood pressure measurement in the upper limb. The 4 groups had a similar baseline ASI, which was greater than the reference range in each group. Although antidiabetic therapies improved hemoglobin A(1c) and low-density lipoprotein cholesterol, ASI only decreased significantly in the pioglitazone group. Thus, pioglitazone improved abnormal arterial stiffness in patients with type 2 diabetes mellitus via a mechanism beyond the metabolic improvement. These findings may have important clinical implications in the use of pioglitazone in patients with type 2 diabetes mellitus.

  7. Apigenin Inhibits Pancreatic Stellate Cell Activity in Pancreatitis

    Science.gov (United States)

    Mrazek, Amy A.; Porro, Laura J.; Bhatia, Vandanajay; Falzon, Miriam; Spratt, Heidi; Zhou, Jia; Chao, Celia; Hellmich, Mark R.

    2015-01-01

    BACKGROUND Chronic pancreatitis (CP) is characterized by recurrent pancreatic injury, resulting in inflammation, necrosis, and fibrosis. There are currently no drugs limiting pancreatic fibrosis associated with CP, and there is a definite need to fill this void in patient care. MATERIALS AND METHODS Pancreatitis was induced in C57/BL6 mice using supraphysiologic doses of cerulein (CR), and apigenin treatment (once daily, 50 μg/mouse by oral gavage) was initiated one week into the recurrent acute pancreatitis (RAP) protocol. Pancreata were harvested after four weeks of RAP. Immunostaining with fibronectin antibody was used to quantify the extent of pancreatic fibrosis. To assess how apigenin may decrease organ fibrosis, we evaluated the effect of apigenin on the proliferation and apoptosis of human pancreatic stellate cells (PSCs) in vitro. Lastly, we assessed apigenin’s effect on gene expression in PSCs stimulated with parathyroid hormone related protein (PTHrP), a pro-fibrotic and pro-inflammatory mediator of pancreatitis, using RT-PCR. RESULTS After four weeks of RAP, apigenin significantly reduced the fibrotic response to injury while preserving acinar units. Apigenin inhibited viability and induced apoptosis of PSCs in a time and dose-dependent manner. Lastly, apigenin reduced PTHrP-stimulated increases in the PSC mRNA expression levels of extracellular matrix proteins collagen 1A1 and fibronectin, proliferating cell nuclear antigen, TGF-β, and IL-6. CONCLUSIONS These in vivo and in vitro studies provide novel insights regarding apigenin’s mechanism(s) of action in reducing the severity of RAP. Additional preclinical testing of apigenin analogs is warranted to develop a therapeutic agent for patients at risk for CP. PMID:25799526

  8. The association of pioglitazone and urinary tract disease in type 2 diabetic Taiwanese: bladder cancer and chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Mei-Yueh Lee

    Full Text Available OBJECTIVE: Although studies have shown an association between pioglitazone and bladder cancer, the associated factors have not been identified. The aim of this study was to investigate the factors that may link pioglitazone to bladder cancer. MATERIALS AND METHODS: In total, 34,970 study subjects were identified from the National Health Insurance Research Database in 2003 with follow-up from 2005 to 2009. The demographic characteristics of patients who had used and had never used pioglitazone, including age, sex, diabetes duration, urinary tract disease, nephropathy, bladder cancer, and cumulative dose and duration of pioglitazone therapy, were analyzed using the χ2 test. Cox proportional hazard regression models were used to determine the independent effects of pioglitazone on bladder cancer and newly developed chronic kidney disease. RESULTS: Among 3,497 ever users and 31,473 never users of pioglitazone, the respective incident cases of bladder cancer were 12 (0.4% and 72 (0.2%, and for newly developed chronic kidney disease 245 (8.1% and 663 (2.3%, respectively. Ever use of pioglitazone [1.59(1.32-1.91], cumulative dose of pioglitazone 10,500 mg [1.34 (1.04-1.73], and duration of therapy 12 months [1.39 (1.09-1.76] were associated with the development of chronic kidney disease. CONCLUSIONS: There was no association of pioglitazone use with bladder cancer development, however, there was an association with an increased risk of newly developed chronic kidney disease.

  9. A Suspicious Pancreatic Mass in Chronic Pancreatitis: Pancreatic Actinomycosis

    Directory of Open Access Journals (Sweden)

    F. de Clerck

    2015-01-01

    Full Text Available Introduction. Pancreatic actinomycosis is a chronic infection of the pancreas caused by the suppurative Gram-positive bacterium Actinomyces. It has mostly been described in patients following repeated main pancreatic duct stenting in the context of chronic pancreatitis or following pancreatic surgery. This type of pancreatitis is often erroneously interpreted as pancreatic malignancy due to the specific invasive characteristics of Actinomyces. Case. A 64-year-old male with a history of chronic pancreatitis and repeated main pancreatic duct stenting presented with weight loss, fever, night sweats, and abdominal pain. CT imaging revealed a mass in the pancreatic tail, invading the surrounding tissue and resulting in splenic vein thrombosis. Resectable pancreatic cancer was suspected, and pancreatic tail resection was performed. Postoperative findings revealed pancreatic actinomycosis instead of neoplasia. Conclusion. Pancreatic actinomycosis is a rare type of infectious pancreatitis that should be included in the differential diagnosis when a pancreatic mass is discovered in a patient with chronic pancreatitis and prior main pancreatic duct stenting. Our case emphasizes the importance of pursuing a histomorphological confirmation.

  10. Pancreatic Cysts

    Science.gov (United States)

    ... be cancerous when found. Intraductal papillary mucinous neoplasm (IPMN) is a growth in the main pancreatic duct or one of its side branches. IPMN may be precancerous or cancerous. It occurs most ...

  11. Chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Maisonneuve, Patrick; Lowenfels, Albert B

    2002-01-01

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

  12. Pancreatic Cancer Early Detection Program

    Science.gov (United States)

    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

  13. Chronic Pancreatitis and Pancreatic Cancer Risk

    DEFF Research Database (Denmark)

    Kirkegård, Jakob; Mortensen, Frank Viborg; Cronin-Fenton, Deirdre

    2017-01-01

    Chronic pancreatitis is a putative risk factor for pancreatic cancer. The aim of this study was to examine the magnitude and temporality of this association. We searched MEDLINE and EMBASE for observational studies investigating the association between chronic pancreatitis and pancreatic cancer. We...... computed overall effect estimates (EEs) with associated 95% confidence intervals (CIs) using a random-effects meta-analytic model. The EEs were stratified by length of follow-up from chronic pancreatitis diagnosis to pancreatic cancer (lag period). Robustness of the results was examined in sensitivity...... analyses. We identified 13 eligible studies. Pooled EEs for pancreatic cancer in patients with chronic pancreatitis were 16.16 (95% CI: 12.59-20.73) for patients diagnosed with pancreatic cancer within 2 years from their chronic pancreatitis diagnosis. The risk of pancreatic cancer in patients with chronic...

  14. Effects of pioglitazone and fenofibrate co-administration on bone biomechanics and histomorphometry in ovariectomized rats.

    Science.gov (United States)

    Smith, Susan Y; Samadfam, Rana; Chouinard, Luc; Awori, Malaika; Bénardeau, Agnes; Bauss, Frieder; Guldberg, Robert E; Sebokova, Elena; Wright, Matthew B

    2015-11-01

    Pioglitazone, the peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist is an effective therapy for type 2 diabetes, but has been associated with increased risk for bone fracture. Preclinical studies suggest that PPAR-α agonists (e.g., fenofibrate) increase bone mineral density/content, although clinical data on bone effects of fibrates are lacking. We investigated the effects of pioglitazone (10 mg/kg/day) and fenofibrate (25 mg/kg/day) on bone strength and bone histomorphometric parameters in osteopenic ovariectomized (OVX) rats. An additional group of rats received a combination of pioglitazone + fenofibrate to mimic the effects of a dual PPAR-α/γ agonist. The study consisted of a 13-week treatment phase followed by a 6-week treatment-free recovery period. Pioglitazone significantly reduced biomechanical strength at the lumbar spine and femoral neck compared with rats administered fenofibrate. Co-treatment with pioglitazone + fenofibrate had no significant effect on bone strength in comparison with OVX vehicle controls. Histomorphometric analysis of the proximal tibia revealed that pioglitazone suppressed bone formation and increased bone resorption at both cancellous and cortical bone sites relative to OVX vehicle controls. In contrast, fenofibrate did not affect bone resorption and only slightly suppressed bone formation. Discontinuation of pioglitazone treatment, both in the monotherapy and in the combination therapy arms, resulted in restoration of bone formation and resorption rates, demonstrating reversibility of effects. The above data support the concept that dual activation of PPAR-γ and PPAR-α attenuates the negative effects of PPAR-γ agonism on bone strength.

  15. Beneficial effects of pioglitazone on retardation of persistent atrial fibrillation progression in diabetes mellitus patients.

    Science.gov (United States)

    Liu, Bing; Wang, Jiancheng; Wang, Guoxing

    2014-01-01

    This study aimed to explore the effects of pioglitazone treatment on progression from persistent atrial fibrillation (AF) to permanent atrial fibrillation in diabetes mellitus (DM) patients and to investigate the possible mechanisms involved in those effects.A total of 146 diabetes mellitus (DM) patients with firstly identified persistent AF were selected. Seventy patients were randomized into the pioglitazone (30 mg/day) group and 76 into the placebo group. Pro-collagen type I carboxyterminal peptide (PICP), advanced glycation end products (AGEs), and angiotensin II were assayed and left atrial diameter (LA diameter) was measured at the first presence of persistent AF, and at 6 and 14 months of follow-up. The time point of identification of permanent AF and the incidence of permanent AF in the patients were all recorded.Thirty-seven (49%) of the 76 patients in the placebo group and 21 (30%) of the 70 patients in the pioglitazone group progressed to permanent AF (P = 0.028). No significant differences existed in the follow-up time (20.5 ± 3.97 months for pioglitazone group versus 20.9 ± 4.14 months for placebo group) between the two groups (P = 0.535). In the pioglitazone group, no significant change was found in angiotensin II level. The PICP level did not change significantly at 6-months of follow-up, but decreased significantly at 14-months of follow-up (P = 0.032). The AGE (P = 0.037 at 6-month follow-up, P pioglitazone treatment may decrease the incidence of permanent AF in DM patients with persistent AF, which may be associated with the suppressing effect of pioglitazone on AGEs.

  16. Effect of low dose pioglitazone on glycemic control and insulin resistance in Type 2 diabetes: A randomized, double blind, clinical trial.

    Science.gov (United States)

    Rajagopalan, Sujit; Dutta, Pinaki; Hota, Debasish; Bhansali, Anil; Srinivasan, Anand; Chakrabarti, Amitava

    2015-09-01

    This study shows that pioglitazone 7.5 mg/day as an add-on therapy in Southeast Asian patients with Type 2 diabetes is safer and equally efficacious as the 15- and 30-mg doses of pioglitazone. Hence it is prudent to start pioglitazone therapy at a lower dose of 7.5 mg/day.

  17. Beneficial effects of canagliflozin in combination with pioglitazone on insulin sensitivity in rodent models of obese type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Yoshinori Watanabe

    Full Text Available Despite its insulin sensitizing effects, pioglitazone may induce weight gain leading to an increased risk of development of insulin resistance. A novel sodium glucose co-transporter 2 (SGLT2 inhibitor, canagliflozin, provides not only glycemic control but also body weight reduction through an insulin-independent mechanism. The aim of this study was to investigate the combined effects of these agents on body weight control and insulin sensitivity.Effects of combination therapy with canagliflozin and pioglitazone were evaluated in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF rats.In the KK-Ay mice, the combination therapy further improved glycemic control compared with canagliflozin or pioglitazone monotherapy. Furthermore, the combination significantly attenuated body weight and fat gain induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early intervention with pioglitazone monotherapy almost completely prevented the progressive development of hyperglycemia, and no further improvement was observed by add-on treatment with canagliflozin. However, the combination significantly reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda index, suggesting improved whole-body insulin sensitivity.Our study indicates that combination therapy with canagliflozin and pioglitazone improves insulin sensitivity partly by preventing glucotoxicity and, at least partly, by attenuating pioglitazone-induced body weight gain in two different obese diabetic animal models. This combination therapy may prove to be a valuable option for the treatment and prevention of obese type 2 diabetes.

  18. Beneficial effects of canagliflozin in combination with pioglitazone on insulin sensitivity in rodent models of obese type 2 diabetes.

    Science.gov (United States)

    Watanabe, Yoshinori; Nakayama, Keiko; Taniuchi, Nobuhiko; Horai, Yasushi; Kuriyama, Chiaki; Ueta, Kiichiro; Arakawa, Kenji; Senbonmatsu, Takaaki; Shiotani, Masaharu

    2015-01-01

    Despite its insulin sensitizing effects, pioglitazone may induce weight gain leading to an increased risk of development of insulin resistance. A novel sodium glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin, provides not only glycemic control but also body weight reduction through an insulin-independent mechanism. The aim of this study was to investigate the combined effects of these agents on body weight control and insulin sensitivity. Effects of combination therapy with canagliflozin and pioglitazone were evaluated in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF) rats. In the KK-Ay mice, the combination therapy further improved glycemic control compared with canagliflozin or pioglitazone monotherapy. Furthermore, the combination significantly attenuated body weight and fat gain induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early intervention with pioglitazone monotherapy almost completely prevented the progressive development of hyperglycemia, and no further improvement was observed by add-on treatment with canagliflozin. However, the combination significantly reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda index, suggesting improved whole-body insulin sensitivity. Our study indicates that combination therapy with canagliflozin and pioglitazone improves insulin sensitivity partly by preventing glucotoxicity and, at least partly, by attenuating pioglitazone-induced body weight gain in two different obese diabetic animal models. This combination therapy may prove to be a valuable option for the treatment and prevention of obese type 2 diabetes.

  19. Beneficial Effects of Canagliflozin in Combination with Pioglitazone on Insulin Sensitivity in Rodent Models of Obese Type 2 Diabetes

    Science.gov (United States)

    Watanabe, Yoshinori; Nakayama, Keiko; Taniuchi, Nobuhiko; Horai, Yasushi; Kuriyama, Chiaki; Ueta, Kiichiro; Arakawa, Kenji; Senbonmatsu, Takaaki; Shiotani, Masaharu

    2015-01-01

    Background Despite its insulin sensitizing effects, pioglitazone may induce weight gain leading to an increased risk of development of insulin resistance. A novel sodium glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin, provides not only glycemic control but also body weight reduction through an insulin-independent mechanism. The aim of this study was to investigate the combined effects of these agents on body weight control and insulin sensitivity. Methods Effects of combination therapy with canagliflozin and pioglitazone were evaluated in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF) rats. Results In the KK-Ay mice, the combination therapy further improved glycemic control compared with canagliflozin or pioglitazone monotherapy. Furthermore, the combination significantly attenuated body weight and fat gain induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early intervention with pioglitazone monotherapy almost completely prevented the progressive development of hyperglycemia, and no further improvement was observed by add-on treatment with canagliflozin. However, the combination significantly reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda index, suggesting improved whole-body insulin sensitivity. Conclusions Our study indicates that combination therapy with canagliflozin and pioglitazone improves insulin sensitivity partly by preventing glucotoxicity and, at least partly, by attenuating pioglitazone-induced body weight gain in two different obese diabetic animal models. This combination therapy may prove to be a valuable option for the treatment and prevention of obese type 2 diabetes. PMID:25615826

  20. Pioglitazone Lowers Serum Retinol Binding Protein 4 by Suppressing its Expression in Adipose Tissue of Obese Rats

    Directory of Open Access Journals (Sweden)

    Chaoyu Zhu

    2015-01-01

    Full Text Available Background/Aims: Pioglitazone, a peroxisome proliferator-activated receptor γ activator, is clinically used to treat insulin resistance. However, the underlying mechanism of pioglitazone's action remains unclear. We investigated whether, and how, pioglitazone modulates serum level of retinol binding protein 4 (RBP4, an adipocytokine associated with obesity and insulin resistance. Methods: Insulin sensitivity was determined by oral glucose tolerance test, and RBP4 expression was detected by RT-PCR and Western blotting. Results: Pioglitazone treatment significantly decreased serum RBP4 levels in obese rats, which was correlated with reduced body weight and increased insulin sensitivity. Moreover, pioglitazone greatly decreased RBP4 mRNA and protein levels in adipose tissue but not in the liver. Consistently, pioglitazone treatment significantly reduced RBP4 protein expression in 3T3-L1 adipocytes but not in HepG2 cells. Conclusion: These results demonstrate that pioglitazone inhibits the level of serum RPB4 by suppressing RBP4 expression in adipose tissue of obese rats, suggesting that inhibiting RBP4 expression in adipocytes may provide a mechanism by which pioglitazone improves insulin sensitivity in insulin-resistant subjects.

  1. Protective effect of pioglitazone on kidney injury in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hui Peng; Pei-Yu Liang; Shan-Ji Ou; Xiong-Bing Zu

    2014-01-01

    Objective:To investigate the protective effect of pioglitazone on kidney injury in diabetic rat model and its mechanisms.Methods:Forty healthySpragueDawley rats were selected and randomly divided into five groups, with8 rats in each group.GroupA served as control group and were administered with sterile citrate buffer(i.p.) as placebo.GroupsB,C,D andE rats were injected(i.p.) with streptozotocin to induce typeⅠdiabetes.Diabetic rats inGroupB were intragastrically administered with sterile saline solution alone.GroupsC,D andE rats were intragastrically given pioglitazone hydrochloride suspension at doses of10,20,30 mg/kg per day, respectively.After eight weeks of treatment, all rats were anesthetized and blood was withdrawn from the abdominal aortic for detection of hemoglobinA1c, serum creatinine(SCr) and blood urea nitrogen(BUN) levels.Rats were then sacrificed and the left kidney was excised for calculation of kidney hypertrophy index(KHI), observation of renal pathological changes using light microscope and electron microscope.Mean glomerular cross-sectional areas(MGA), mean glomerular volume (MGV), glomerular basement membrane thickness and foot process fusion ratio were calculated. RT-PCR was employed for detection of podocalyxin(PCX) protein expression.Results:Results showed that levels of hemoglobinA1c,BUN,SCr inGroupsB,C,D andE rats were significantly higher than those inGroupA(P<0.05), whileBUN andSCr levels in rats ofGroupsC,D andE were significantly lower than those inGroupB(P<0.05).KHI,MGA andMGV levels were significantly higher inGroupsB,C,D andE rats than those inGroupA(P<0.05);KHI andMGA levels inGroup B rats were significantly higher than those inGroupsC,D andE(P<0.05) andMGV inGroups D andE was significantly lower than that inGroupsB andC(P<0.05).Histology study showed normal glomerulus structure, morphology, volume, endothelial cells and mesangial cells as well as clear glomerular capillary inGroupA rats.Renal mesangial matrix proliferation and

  2. Effect of raw Radix Rehmanniae on the pharmacokinetics of pioglitazone in rats.

    Science.gov (United States)

    Shi, Zhan; Gao, Jingwen; Yuan, Yuemei; Zhu, Shuzhen; Yao, Meicun

    2014-05-01

    Raw Radix Rehmanniae (RRR) is a frequently used traditional Chinese medicine in the treatment of diabetes mellitus according to the statistics on all of the anti-diabetic formulas recorded in New National Traditional Chinese Medicine. Pioglitazone and RRR may be co-administrated for presumably enhanced therapeutic effects because of the common indications. Therefore, the aim of the study was to evaluate the effect of RRR on the pharmacokinetics of pioglitazone in healthy rats and type 2 diabetic rats. The pharmacokinetic effect of RRR on pioglitazone was studied in healthy rats and type 2 diabetic rats. A validated UPLC-MS/MS method was used to analyze the concentration of pioglitazone in blood samples. The pharmacokinetic parameters were calculated using non-compartmental analyses by Winnonlin 5.0.1. In healthy group, the pre-treatment of RRR significantly (Ppioglitazone; whereas in T2DM group, significant increase of C(max) and decrease of V/F and T½ were found after the rats were pre-treated with RRR. However, AUC(0-t) and CL/F remained unchanged in both healthy group and T2DM group. In conclusion, co-administration with RRR could alter the pharmacokinetic profiles of pioglitazone to statistically significant levels.

  3. Pentoxifylline and melatonin in combination with pioglitazone ameliorate experimental non-alcoholic fatty liver disease.

    Science.gov (United States)

    Zaitone, Sawsan; Hassan, Neven; El-Orabi, Naglaa; El-Awady, El-Sayed

    2011-07-15

    Insulin resistance, oxidative stress and cytokine imbalance are key pathophysiological mechanisms in non-alcoholic fatty liver disease (NAFLD). This study aimed at evaluating the effect of treatment with the insulin sensitizer, pioglitazone, the tumor necrosis factor-α inhibitor, pentoxifylline, and the antioxidant, melatonin and their combinations in rats with NAFLD. Rats were fed a high-fat diet (HFD) for eight weeks to induce NAFLD. For an additional eight weeks, rats were fed the HFD along with pioglitazone, pentoxifylline, melatonin alone or in combination. Liver index and insulin resistance index were calculated. Serum liver enzyme activities, total cholesterol, triglycerides and tumor necrosis factor-α (TNF-α) were determined. Tissue triglycerides, malondialdehyde and reduced glutathione were measured and liver injury was evaluated by histopathological examination. HFD induced severe hepatic steatosis, inflammation and fibrosis. In addition, liver index, insulin resistance index, activities of liver enzymes and serum level of total cholesterol, triglycerides and TNF-α were elevated. This was coupled with an increase in tissue triglycerides, malondialdehyde and depletion of reduced glutathione. Pioglitazone, pentoxifylline and melatonin, alone or in combination; reduced the insulin resistance index, activities of liver enzymes, hepatic malondialdehyde and increased hepatic reduced glutathione level. Pentoxifylline led to a decrease in serum TNF-α level, however, pioglitazone and melatonin reduced serum total cholesterol and triglycerides. In conclusion, data in this study indicate that pentoxifylline and melatonin can be used as promising adjuvant therapies to pioglitazone in the clinical management of NAFLD.

  4. Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ.

    Science.gov (United States)

    Zhao, Duo; Zhu, Zhicheng; Li, Dan; Xu, Rihao; Wang, Tiance; Liu, Kexiang

    2015-11-17

    Cardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Pioglitazone, the widely used thiazolidinedione, is shown to be efficient in the prevention of cardiovascular complications of T2DM. In this study, we report that pioglitazone inhibits CXCR7 expression and thus blocks chemotaxis in differentiated macrophage without perturbing cell viability or macrophage differentiation. In addition, pioglitazone-mediated CXCR7 suppression and chemotaxis inhibition occur via activating peroxisome proliferator-activated receptor γ (PPARγ) but not PPARα in differentiated macrophage. More importantly, pioglitazone therapy-induced PPARγ activation suppresses CXCR7 expression in human carotid atherosclerotic lesions. Collectively, our data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ.

  5. Effects of red mold dioscorea with pioglitazone, a potentially functional food, in the treatment of diabetes

    Directory of Open Access Journals (Sweden)

    Chien-Li Chen

    2015-12-01

    Full Text Available The prevalence of type 2 diabetes mellitus is increasing rapidly, and its treatment with pioglitazone is likely to induce rhabdomyolysis. We aimed to determine the effect of cotreatment with pioglitazone and red mold dioscorea (RMD produced by Monascus purpureus NTU 568 on pancreas function in streptozotocin (STZ-induced diabetic rats. In diabetic rats fed RMD, RMD with pioglitazone, and pioglitazone alone, insulin concentrations increased significantly by 18.6–40.4%, 64.0–100.0%, and 52.8%, respectively, compared with that in the diabetic group (p < 0.05. Oral glucose tolerance was impaired in the STZ-induced diabetic group within 4 weeks, however, oral glucose tolerance in rats treated with RMD or RMD with pioglitazone improved after 4 weeks, 6 weeks, and 8 weeks. Findings from this study might lend support to the use of RMD as a novel functional food for the prevention of diabetes.

  6. Pioglitazone improves the cardio-ankle vascular index in patients with type 2 diabetes mellitus treated with metformin

    Directory of Open Access Journals (Sweden)

    Ohira M

    2014-07-01

    Full Text Available Masahiro Ohira,1 Takashi Yamaguchi,1 Atsuhito Saiki,1 Noriko Ban,1 Hidetoshi Kawana,1 Ayako Nagumo,1 Takeyoshi Murano,2 Kohji Shirai,3 Ichiro Tatsuno1 1Center for Diabetes, Endocrinology and Metabolism, 2Department of Clinical Laboratory Medicine, 3Department of Vascular Function, Sakura Hospital, Toho University Medical Center, Chiba, Japan Background: Type 2 diabetes is known to be associated with elevated cardiovascular mortality. Pioglitazone improves blood pressure (BP and pulse wave velocity (PWV, which is an arterial stiffness parameter. Arterial stiffness is closely associated with cardiovascular disease. However, PWV is correlated with BP. The cardio-ankle vascular index (CAVI reflects arterial stiffness independent of BP. Pioglitazone improves PWV but reduces blood pressure. The aim of this study was to re-evaluate the effect of pioglitazone on arterial stiffness with CAVI. Methods: Sixty patients with type 2 diabetes mellitus and already on 500 mg/day of metformin received add-on therapy of pioglitazone 15 mg/day or glimepiride 1 mg/day for 6 months, during which time changes in their metabolic parameters and CAVI were observed. Results: After 6 months of treatment, both pioglitazone (n=30 and glimepiride (n=30 improved fasting blood glucose and glycated hemoglobin. The changes in fasting blood glucose and glycated hemoglobin between the two groups were greater in the pioglitazone group. Systolic and diastolic BP was decreased in both groups, with no significant between-group differences. Only pioglitazone increased serum adiponectin levels, and the change in adiponectin between the pioglitazone and glimepiride groups was significantly different. CAVI was decreased significantly by pioglitazone but remained unchanged after treatment with glimepiride. The change in CAVI between the two groups was significantly different. Conclusion: These results suggest that pioglitazone improves CAVI, a BP-independent arterial stiffness parameter

  7. Pioglitazone Improves Mitochondrial Function in the Remnant Kidney and Protects against Renal Fibrosis in 5/6 Nephrectomized Rats

    Directory of Open Access Journals (Sweden)

    Li Sun

    2017-08-01

    Full Text Available Pioglitazone is a type of peroxisome proliferator-activated receptor γ (PPARγ agonist and has been demonstrated to be effective in chronic kidney diseases (CKD treatment. However, the underlying mechanism involved in the renoprotection of pioglitazone has not been fully revealed. In the present study, the renoprotective mechanism of pioglitazone was investigated in 5/6 nephrectomized (Nx rats and TGF-β1-exposed HK-2 cells. Pioglitazone attenuated renal injury and improved renal function, as examined by 24 h urinary protein, blood urea nitrogen and plasma creatinine in Nx rats. Renal fibrosis and enhanced expressions of profibrotic proteins TGF-β1, fibronectin and collagen I caused by Nx were significantly alleviated by pioglitazone. In addition, pioglitazone protected mitochondrial functions by stabilizing the mitochondrial membrane potential, inhibiting ROS generation, maintaining ATP production and the activities of complexes I and III, and preventing cytochrome C leakage from mitochondria. Pioglitazone also upregulated the expression levels of ATP synthase β, COX I and NDUFB8, which were downregulated in the kidney of Nx rats and TGF-β1-exposed HK-2 cells. Furthermore, pioglitazone increased fusion proteins Opa-1 and Mfn2 expressions and decreased fission protein Drp1 expression. The results imply that pioglitazone may exert the renoprotective effects through modulating mitochondrial electron transport chain and mitochondrial dynamics in CKD. Finally, these recoveries were completely or partly inhibited by GW9662, which suggests that these effects at least partly PPARγ dependent. This study provides evidence for the pharmacological mechanism of pioglitazone in the treatment of CKD.

  8. Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice.

    Science.gov (United States)

    Takada, Shingo; Hirabayashi, Kagami; Kinugawa, Shintaro; Yokota, Takashi; Matsushima, Shouji; Suga, Tadashi; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Mizushima, Wataru; Masaki, Yoshihiro; Furihata, Takaaki; Katsuyama, Ryoichi; Okita, Koichi; Tsutsui, Hiroyuki

    2014-10-05

    We have reported that exercise capacity is reduced in high fat diet (HFD)-induced diabetic mice, and that this reduction is associated with impaired mitochondrial function in skeletal muscle (SKM). However, it remains to be clarified whether the treatment of diabetes ameliorates the reduced exercise capacity. Therefore, we examined whether an insulin-sensitizing drug, pioglitazone, could improve exercise capacity in HFD mice. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated with or without pioglitazone (3 mg/kg/day) to yield the following 4 groups: ND+vehicle, ND+pioglitazone, HFD+vehicle, and HFD+pioglitazone (n=10 each). After 8 weeks, body weight, plasma glucose, and insulin in the HFD+vehicle were significantly increased compared to the ND+vehicle group. Pioglitazone normalized the insulin levels in HFD-fed mice, but did not affect the body weight or plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in the HFD+vehicle, and this reduction was almost completely ameliorated in HFD+pioglitazone mice. ADP-dependent mitochondrial respiration, complex I and III activities, and citrate synthase activity were significantly decreased in the SKM of the HFD+vehicle animals, and these decreases were also attenuated by pioglitazone. NAD(P)H oxidase activity was significantly increased in the HFD+vehicle compared with the ND+vehicle, and this increase was ameliorated in HFD+pioglitazone mice. Pioglitazone improved the exercise capacity in diabetic mice, which was due to the improvement in mitochondrial function and attenuation of oxidative stress in the SKM. Our data suggest that pioglitazone may be useful as an agent for the treatment of diabetes mellitus.

  9. Pancreatic Diseases

    Science.gov (United States)

    ... digestive enzymes start digesting the pancreas itself Pancreatic cancer Cystic fibrosis, a genetic disorder in which thick, sticky mucus can also block tubes in your pancreas The pancreas also plays a role in diabetes. In type 1 diabetes, the beta cells of ...

  10. Pancreatic pseudocyst

    Institute of Scientific and Technical Information of China (English)

    Samir Habashi; Peter V Draganov

    2009-01-01

    Pancreatic pseudocysts are complications of acute or chronic pancreatitis. Initial diagnosis is accomplished most often by cross-sectional imaging. Endoscopic ultrasound with fine needle aspiration has become the preferred test to help distinguish pseudocyst from other cystic lesions of the pancreas. Most pseudocysts resolve spontaneously with supportive care. The size of the pseudocyst and the length of time the cyst has been present are poor predictors for the potential of pseudocyst resolution or complications, but in general, larger cysts are more likely to be symptomatic or cause complications. The main two indications for some type of invasive drainage procedure are persistent patient symptoms or the presence of complications (infection, gastric outlet or biliary obstruction, bleeding). Three different strategies for pancreatic pseudocysts drainage are available: endoscopic (transpapillary or transmural) drainage, percutaneous catheter drainage, or open surgery. To date, no prospective controlled studies have compared directly these approaches. As a result, the management varies based on local expertise, but in general, endoscopic drainage is becoming the preferred approach because it is less invasive than surgery, avoids the need for external drain, and has a high long-term success rate. A tailored therapeutic approach taking into consideration patient preferences and involving multidisciplinary team of therapeutic endoscopist, interventional radiologist and pancreatic surgeon should be considered in all cases.

  11. Anti-diabetic properties of a non-conventional radical scavenger, as compared to pioglitazone and exendin-4, in streptozotocin-nicotinamide diabetic mice.

    Science.gov (United States)

    Novelli, Michela; Canistro, Donatella; Martano, Manuela; Funel, Niccola; Sapone, Andrea; Melega, Simone; Masini, Matilde; De Tata, Vincenzo; Pippa, Anna; Vecoli, Cecilia; Campani, Daniela; De Siena, Rocco; Soleti, Antonio; Paolini, Moreno; Masiello, Pellegrino

    2014-04-15

    We previously showed that the innovative radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) improves metabolic dysfunctions in a diabetic mouse model. Here, we compared the in vivo effects of IAC with those of the anti-diabetic drugs pioglitazone (PIO) and exendin-4 (EX-4). Diabetes was induced in C57Bl/6J mice by streptozotocin and nicotinamide administration. Paralleled by healthy controls, diabetic animals (D) were randomly assigned to four groups and treated daily for 7 consecutive weeks: D+saline, ip; D+IAC 30mg/kgb.w., ip; D+PIO 10mg/kgb.w. per os; and D+EX-4, 50μg/kgb.w., ip. Our results show that IAC reduced basal hyperglycemia and improved glucose tolerance better than PIO or EX-4. Interestingly, in the heart of diabetic mice, IAC treatment normalized the increased levels of GSSG/GSH ratio and thiobarbituric acid reactive substances, indexes of oxidative stress and damage, while PIO and EX-4 were less effective. As supported by immunohistochemical data, IAC markedly prevented diabetic islet β-cell reduced density, differently from PIO and EX-4 that had only a moderate effect. Interestingly, in diabetic animals, IAC treatment enhanced the activity of pancreatic-duodenal homeobox 1 (PDX-1), an oxidative stress-sensitive transcription factor essential for maintenance of β-cell function, as evaluated by quantification of its nuclear immunostaining, whereas PIO or EX-4 treatments did not. Altogether, these observations support the improvement of the general redox balance and β-cell function induced by IAC treatment in streptozotocin-nicotinamide diabetic mice. Furthermore, in this model, the correction of diabetic alterations was better obtained by treatment with the radical scavenger IAC than with pioglitazone or exendin-4.

  12. Prevention of diabetes with pioglitazone in ACT NOW: physiologic correlates.

    Science.gov (United States)

    Defronzo, Ralph A; Tripathy, Devjit; Schwenke, Dawn C; Banerji, Maryann; Bray, George A; Buchanan, Thomas A; Clement, Stephen C; Gastaldelli, Amalia; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Ratner, Robert E; Stentz, Frankie B; Musi, Nicolas; Reaven, Peter D

    2013-11-01

    We examined the metabolic characteristics that attend the development of type 2 diabetes (T2DM) in 441 impaired glucose tolerance (IGT) subjects who participated in the ACT NOW Study and had complete end-of-study metabolic measurements. Subjects were randomized to receive pioglitazone (PGZ; 45 mg/day) or placebo and were observed for a median of 2.4 years. Indices of insulin sensitivity (Matsuda index [MI]), insulin secretion (IS)/insulin resistance (IR; ΔI0-120/ΔG0-120, ΔIS rate [ISR]0-120/ΔG0-120), and β-cell function (ΔI/ΔG × MI and ΔISR/ΔG × MI) were calculated from plasma glucose, insulin, and C-peptide concentrations during oral glucose tolerance tests at baseline and study end. Diabetes developed in 45 placebo-treated vs. 15 PGZ-treated subjects (odds ratio [OR] 0.28 [95% CI 0.15-0.49]; P IGT > T2DM) was associated with improvements in insulin sensitivity (OR 0.61 [95% CI 0.54-0.80]), IS (OR 0.61 [95% CI 0.50-0.75]), and β-cell function (ln IS/IR index and ln ISR/IR index) (OR 0.26 [95% CI 0.19-0.37]; all P < 0.0001). Of the factors measured, improved β-cell function was most closely associated with final glucose tolerance status.

  13. Ny klassifikation af pancreatitis acuta

    DEFF Research Database (Denmark)

    Hansen, Benny Østerbye; Schmidt, Palle Nordblad

    2011-01-01

    The course of acute pancreatitis is in the initial phase dominated by a systemic inflammatory response, later by local complications. A new classification defines three specific types of pancreatitis: 1) interstitial oedematous pancreatitis and 2) necrotizing pancreatitis with pancreatic...

  14. Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats

    Science.gov (United States)

    Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung

    2016-01-01

    Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model. PMID:27997588

  15. Pioglitazone in adult rats reverses immediate postnatal overfeeding-induced metabolic, hormonal, and inflammatory alterations.

    Science.gov (United States)

    Boullu-Ciocca, S; Tassistro, V; Dutour, A; Grino, M

    2015-12-01

    Immediate postnatal overfeeding in rats, obtained by reducing the litter size, results in early-onset obesity. Such experimental paradigm programs overweight, insulin resistance, dyslipidemia, increased adipose glucocorticoid metabolism [up-regulation of glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)], and overexpression of proinflammatory cytokines in mesenteric adipose tissue (MAT) in adulthood. We studied the effects of pioglitazone, a PPARγ agonist, treatment on the above-mentioned overfeeding-induced alterations. Nine-month-old rats normofed or overfed during the immediate postnatal period were given pioglitazone (3 mg/kg/day) for 6 weeks. Pioglitazone stimulated weight gain and induced a redistribution of adipose tissue toward epididymal location with enhanced plasma adiponectin. Treatment normalized postnatal overfeeding-induced metabolic alterations (increased fasting insulinemia and free fatty acids) and mesenteric overexpression of GR, 11β-HSD11, CD 68, and proinflammatory cytokines mRNAs, including plasminogen-activator inhibitor type 1. Mesenteric GR mRNA levels correlated positively with mesenteric proinflammatory cytokines mRNA concentrations. In vitro incubation of MAT obtained from overfed rats demonstrated that pioglitazone induced a down-regulation of GR gene expression and normalized glucocorticoid-induced stimulation of 11β-HSD1 and plasminogen-activator inhibitor type 1 mRNAs. Our data show for the first time that the metabolic, endocrine, and inflammatory alterations induced by early-onset postnatal obesity can be reversed by pioglitazone at the adulthood. They demonstrate that pioglitazone, in addition to its well-established effect on adipose tissue redistribution and adiponectin secretion, reverses programing-induced adipose GR, 11β-HSD1, and proinflammatory cytokines overexpression, possibly through a GR-dependent mechanism.

  16. Effect of pioglitazone treatment in a patient with secondary multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Pershadsingh Harrihar A

    2004-04-01

    Full Text Available Abstract Background Ligands of the peroxisome proliferator-activated receptor-gamma (PPARγ induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. Preclinical studies have shown that the thiazolidinedione pioglitazone, an FDA-approved PPARγ agonist used to treat type 2 diabetes, delays the onset and reduces the severity of clinical symptoms in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a patient with secondary MS. Case presentation The rationale and risks of taking pioglitazone were carefully explained to the patient, consent was obtained, and treatment was initiated at 15 mg per day p.o. and then increased by 15 mg biweekly to 45 mg per day p.o. for the duration of the treatment. Safety was assessed by measurements of metabolic profiles, blood pressure, and edema; effects on clinical symptoms were assessed by measurement of cognition, motor function and strength, and MRI. Within 4 weeks the patient exhibited increased appetite, cognition and attention span. After 12 months treatment, body weight increased from 27.3 to 35.9 kg (32% and maintained throughout the duration of the study. Upper extremity strength and coordination improved, and increased fine coordination was noted unilaterally after 8 months and bilaterally after 15 months. After 8 months therapy, the patient demonstrated improvement in orientation, short-term memory, and attention span. MRIs carried out after 10 and 18 months of treatment showed no perceptible change in overall brain atrophy, extent of demyelination, or in Gd-enhancement. After 3.0 years on pioglitazone, the patient continues to be clinically stable, with no adverse events. Conclusions In a patient with secondary progressive MS, daily treatment with 45 mg p.o. pioglitazone for 3 years induced apparent clinical improvement without adverse events

  17. Pancreatic Rest or Not? The Debate on the Nutrition in Acute Pancreatitis Continues...

    Directory of Open Access Journals (Sweden)

    Generoso Uomo

    2013-03-01

    Full Text Available Acute pancreatitis creates a catabolic stress state promoting a systemic inflammatory response and nutritional deterioration; as a consequence, adequate supply of nutrients plays an important role in recovery [1]. Up to the 1990s, total parenteral nutrition and gastrointestinal tract rest have been comprehensively recommended in acute pancreatitis, which make pancreas at rest to reduce pancreatic exocrine secretion and also meet nutritional need [2, 3, 4]. Afterwards, several studies showed that intestinal mucosa undergoes atrophy during oral fasting, which would induce bacteria translocation in gastrointestinal tract and cause pancreatic necrotic tissue infection [5, 6]. According to this, animal experiments and human studies have shown that enteral nutrition is safe and can preserve the integrity of intestinal mucosa to decrease the incidence of infectious complications and other severe complications, such as multiple organ deficiency syndrome [4]. Furthermore, enteral nutrition does not stimulate pancreatic exocrine secretion, if the feeding tube is positioned in the jejunum by nasojejunal or jejunostomy routes.

  18. Chronic Pancreatitis in Children

    Science.gov (United States)

    ... maintaining good health. Can chronic pancreatitis give my child cancer? If your child has chronic pancreatitis, he or she will be at an increased risk of developing pancreatic cancer compared to the general population. The degree of ...

  19. Acute Pancreatitis Secondary to Pancreatic Neuroendocrine Tumours

    Directory of Open Access Journals (Sweden)

    Grinó P

    2003-03-01

    Full Text Available CONTEXT: Pancreatic neoplasms are an uncommon aetiology of acute pancreatitis. Pancreatic neuroendocrine tumours are a rare subgroup of pancreatic neoplasms. CASE REPORT: We report on three patients having acute pancreatitis secondary to pancreatic neuroendocrine tumours, one of them with severe pancreatitis, and review the published cases up to now. Only 22 patients with acute pancreatitis secondary to pancreatic neuroendocrine tumours have been reported (including the present cases. Most of these cases were of non-functioning neoplasms and the course of the pancreatitis tended to be mild. In the most recent reports and in the present cases, the initial diagnostic method was CT scan. Less than half had metastases when the tumour was diagnosed and mortality from these neoplasms reached approximately 50%. CONCLUSIONS: Pancreatic neuroendocrine tumours can cause acute pancreatitis even in patients under 50 years of age. On many occasions, the tumours are non-functioning; therefore, acute pancreatitis may be the first clinical symptom. Consequently, faced with acute pancreatitis of unknown origin, a non-functioning neuroendocrine tumour should be ruled out.

  20. Effects of pioglitazone on serum leptin and adiponectin in polycystic ovary syndrome patients with insulin resistance

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To investigate the effects of pioglitazone on serum leptin and adiponectin in polycystic ovary syndrome(PCOS)patients with insulin resistance(IR).Methods Thirty-five PCOS patients with IR were treated with pioglitazone 15mg/d for 12 weeks.The results of ovulation induction were observed.The changes of fasting plasma glucose(FPG),fasting serum insulin(FINS),serum levels of leptin,adiponectin,follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T)and blood fat were examined at the ...

  1. Effect of pioglitazone on glucose metabolism and luteinizing hormone secretion in women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Hermann, Anne Pernille; Andersen, Marianne

    2006-01-01

    OBJECTIVE: To thoroughly examine the mechanisms for insulin resistance in polycystic ovary syndrome (PCOS) and to evaluate the effects of pioglitazone treatment on insulin resistance, beta-cell function, LH secretion, and glucose metabolism. DESIGN: Randomized, blinded, placebo-controlled study....... SETTING: Outpatient clinic, at a university hospital in Denmark. PATIENT(S): Thirty obese women with PCOS and 14 weight-matched healthy females. INTERVENTION(S): Sixteen weeks of blinded treatment with pioglitazone (30 mg/d) or placebo. MAIN OUTCOME MEASURE(S): Fasting blood samples, 24-hour 20-minute...

  2. 保留十二指肠胰头切除术治疗胰头部肿块型慢性胰腺炎的疗效%Efficacy of duodenum-preserving pancreatic head resection for chronic pancreatitis with mass in the head of the pancreas

    Institute of Scientific and Technical Information of China (English)

    孙诚谊; 朱海涛

    2014-01-01

    Objective To investigate the clinical efficacy of two types of duodenum-preserving pancreatic head resection (Beger procedure and Berne procedure) for chronic pancreatitis with mass in the head of the pancreas.Methods The clinical data of 46 patients with chronic pancreatitis and mass in the head of the pancreas who were admitted to the Affiliated Hospital of Guiyang Medical College from September 2008 to April 2012 were retrospectively analyzed.There were 24 patients received Beger procedure (Beger group),and 22 received Beme procedure (Berne group).The complications,life quality and pain after the operation were evaluated.Patients were followed up via phone call and out-patient examination till April 2013.The measurement data were analyzed using the Mann-Whitney U test,and the constituent ratios were compared using the chi-square test.Results The operation time and volume of blood loss were (377 ± 21) minutes and (746 ± 129) mL in the Beger group,and (323 ± 17) minutes and (577 ± 111)mL in the Berne group,with significant difference between the 2 groups (U=14.0,88.0,P <0.05).Four patients in the Beger group and 1 in the Berne group were complicated with pancreatic leakage,with no significant difference between the 2 groups (x2=0.714,P > 0.05).The scores of life quality evaluation (physical condition,work capacity,cognitive ability,emotion,social competence and overall life quality) were 82 ± 14,74±24,90 ± 18,78±20,83 ± 18,73 ± 18 in the Beger group,and 79 ± 16,71 ±20,92 ±21,76 ± 18,80 ±21,70 ± 16 in the Berne group,with no significant difference between the 2 groups (U =177.5,183.5,187.5,178.0,189.5,192.0,P > 0.05).The scores of symptom evaluation (fatigue,nausea and vomitting,pain,anorexia,dyspnea,sleep disorders,obstipation,diarrhea,financial worries) were 28 ± 16,24 ± 10,20±12,23 ± 14,4 ± 1,32 ± 12,6 ±2,18 ± 14,36± 18 in the Beger group,and 26 ± 18,26 ±20,22 ± 16,26 ± 16,3 ± 1,30 ± 10,5 ± 1,16 ± 12,38 ± 20 in the Berne

  3. Duodenal Acidity May Increase the Risk of Pancreatic Cancer in the Course of Chronic Pancreatitis: An Etiopathogenetic Hypothesis

    Directory of Open Access Journals (Sweden)

    Talamini G

    2005-03-01

    Full Text Available Chronic pancreatitis patients have an increased risk of developing pancreatic cancer. The cause of this increase has yet to be fully explained but smoking and inflammation may play an important role. To these, we must now add a new potential risk factor, namely duodenal acidity. Patients with chronic pancreatitis very often present pancreatic exocrine insufficiency combined with a persistently low duodenal pH in the postprandial period. The duodenal mucosa in chronic pancreas patients with pancreatic insufficiency has a normal concentration of s-cells and, therefore, the production of secretin is preserved. Pancreatic ductal cells are largely responsible for the amount of bicarbonate and water secretion in response to secretin stimulation. When gastric acid in the duodenum is not well-balanced by alkaline pancreatic secretions, it may induce a prolonged secretin stimulus which interacts with the pancreatic ductal cells resulting in an increased rate of ductular cell activity and turnover. N-Nitroso compounds from tobacco, identified in human pancreatic juice and known to be important carcinogens, may then act on these active cells, thereby increasing the risk of cancer. Duodenal acidity is probably of particular concern in patients who have undergone a duodenum-preserving pancreatic head resection, since, in this anatomic situation, pancreatic juice transits directly via the jejunal loop, bypassing the duodenum. Patients undergoing a Whipple procedure or side-to-side pancreaticojejunostomy are probably less critically affected because secretions transit, at least in part, via the papilla. If the duodenal acidity hypothesis proves correct, then, in addition to stopping smoking, reduction of duodenal acid load in patients with pancreatic insufficiency may help decrease the risk of pancreatic cancer.

  4. A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Luc Dupuis

    Full Text Available BACKGROUND: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS. METHODS/PRINCIPAL FINDINGS: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio. The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48. Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. CONCLUSION/SIGNIFICANCE: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole. TRIAL REGISTRATION: Clinicaltrials.gov NCT00690118.

  5. Pioglitazone prescription increases risk of bladder cancer in patients with type 2 diabetes: an updated meta-analysis.

    Science.gov (United States)

    He, Shiyao; Tang, Yu-hong; Zhao, Guobin; Yang, Xiaolong; Wang, Dehou; Zhang, Ye

    2014-03-01

    Pioglitazone is widely used for glycemic control in patients with type 2 diabetes mellitus, but evidence regarding the association between pioglitazone and bladder cancer risk is confusing. A systematic search of databases was carried out, and other relevant papers were also identified. Then, the analyses were conducted according to the PRISMA and MOOSE guidelines. After quality assessment, nine datasets from 10 available studies were included on the basis of inclusion criteria. The incidence of bladder cancer among pioglitazone ever users and never users, pooled from four cohort and one randomized studies, were 84.51 and 66.68 per 100,000 person-years, respectively. Nine studies representing 2,596,856 diabetic patients were recognized as eligible for overall study; the result suggested an increased risk of bladder cancer in patients exposed to pioglitazone. A persistent significance was detected after being adjusted by age, gender, and use of other diabetes medications. Subgroup analyses indicated that the significantly increased incidence of bladder cancer was found in men, but not in women. Additionally, the analyses addressing increasing exposure to pioglitazone observed a dose-response relation between exclusive ever use of pioglitazone and bladder cancer in terms of cumulative duration of use and cumulative dosage. With some limitations, our results suggest an increased risk of bladder cancer in diabetic patients using pioglitazone, especially for men with long-term and high-dose exposure. Additional studies are needed to provide more precise evidences to support our results.

  6. Pioglitazone treatment reduces adipose tissue inflammation through reduction of mast cell and macrophage number and by improving vascularity.

    Directory of Open Access Journals (Sweden)

    Michael Spencer

    Full Text Available Adipose tissue in insulin resistant subjects contains inflammatory cells and extracellular matrix components. This study examined adipose pathology of insulin resistant subjects who were treated with pioglitazone or fish oil.Adipose biopsies were examined from nine insulin resistant subjects before/after treatment with pioglitazone 45 mg/day for 12 weeks and also from 19 subjects who were treated with fish oil (1,860 mg EPA, 1,500 mg DHA daily. These studies were performed in a clinical research center setting.Pioglitazone treatment increased the cross-sectional area of adipocytes by 18% (p = 0.01, and also increased capillary density without affecting larger vessels. Pioglitazone treatment decreased total adipose macrophage number by 26%, with a 56% decrease in M1 macrophages and an increase in M2 macrophages. Mast cells were more abundant in obese versus lean subjects, and were decreased from 24 to 13 cells/mm(2 (p = 0.02 in patients treated with pioglitazone, but not in subjects treated with FO. Although there were no changes in total collagen protein, pioglitazone increased the amount of elastin protein in adipose by 6-fold.The PPARγ agonist pioglitazone increased adipocyte size yet improved other features of adipose, increasing capillary number and reducing mast cells and inflammatory macrophages. The increase in elastin may better permit adipocyte expansion without triggering cell necrosis and an inflammatory reaction.

  7. PANCREATIC CANCER

    Directory of Open Access Journals (Sweden)

    Alojz Pleskovič

    2003-12-01

    Full Text Available Background. The pancreatic cancer is quite common malignant tumor of gastointestinal tract and its incidence is increasing in well developed part of the world. Despite of all advanced diagnostic methods the disease is in most cases recognised too late when the tumor is not resectable.Conclusions. Only in 20–30% of patients with pancreatic cancer surgical resection is possible, and even in this group 5year survival is very low. In the patients where the tumor is not resectable, sometimes only palliative procedures are indicated and sometimes only simptomatic therapy is possible. The average survival period in this group of patients is 12–20 months. Adjuvant chemo and radiotherapy has not shown much of benefit and the prognosis is still very bad.

  8. Administration of pioglitazone alone or with alogliptin delays diabetes onset in UCD-T2DM rats.

    Science.gov (United States)

    Cummings, Bethany P; Bettaieb, Ahmed; Graham, James L; Stanhope, Kimber; Haj, Fawaz G; Havel, Peter J

    2014-04-01

    There is a need to identify strategies for type 2 diabetes prevention. Therefore, we investigated the efficacy of pioglitazone and alogliptin alone and in combination to prevent type 2 diabetes onset in UCD-T2DM rats, a model of polygenic obese type 2 diabetes. At 2 months of age, rats were divided into four groups: control, alogliptin (20 mg/kg per day), pioglitazone (2.5 mg/kg per day), and alogliptin+pioglitazone. Non-fasting blood glucose was measured weekly to determine diabetes onset. Pioglitazone alone and in combination with alogliptin lead to a 5-month delay in diabetes onset despite promoting increased food intake and body weight (BW). Alogliptin alone did not delay diabetes onset or affect food intake or BW relative to controls. Fasting plasma glucose, insulin, and lipid concentrations were lower and adiponectin concentrations were threefold higher in groups treated with pioglitazone. All treatment groups demonstrated improvements in glucose tolerance and insulin secretion during an oral glucose tolerance test with an additive improvement observed with alogliptin+pioglitazone. Islet histology revealed an improvement of islet morphology in all treatment groups compared with control. Pioglitazone treatment also resulted in increased expression of markers of mitochondrial biogenesis in brown adipose tissue and white adipose tissue, with mild elevations observed in animals treated with alogliptin alone. Pioglitazone markedly delays the onset of type 2 diabetes in UCD-T2DM rats through improvements of glucose tolerance, insulin sensitivity, islet function, and markers of adipose mitochondrial biogenesis; however, addition of alogliptin at a dose of 20 mg/kg per day to pioglitazone treatment does not enhance the prevention/delay of diabetes onset.

  9. Software preservation

    Directory of Open Access Journals (Sweden)

    Tadej Vodopivec

    2011-01-01

    Full Text Available Comtrade Ltd. covers a wide range of activities related to information and communication technologies; its deliverables include web applications, locally installed programs,system software, drivers, embedded software (used e.g. in medical devices, auto parts,communication switchboards. Also the extensive knowledge and practical experience about digital long-term preservation technologies have been acquired. This wide spectrum of activities puts us in the position to discuss the often overlooked aspect of the digital preservation - preservation of software programs. There are many resources dedicated to digital preservation of digital data, documents and multimedia records,but not so many about how to preserve the functionalities and features of computer programs. Exactly these functionalities - dynamic response to inputs - render the computer programs rich compared to documents or linear multimedia. The article opens the questions on the beginning of the way to the permanent digital preservation. The purpose is to find a way in the right direction, where all relevant aspects will be covered in proper balance. The following questions are asked: why at all to preserve computer programs permanently, who should do this and for whom, when we should think about permanent program preservation, what should be persevered (such as source code, screenshots, documentation, and social context of the program - e.g. media response to it ..., where and how? To illustrate the theoretic concepts given the idea of virtual national museum of electronic banking is also presented.

  10. ERCP in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jijo V Cherian; Joye Varghese Selvaraj; Rajesh Natrayan; Jayanthi Venkataraman

    2007-01-01

    BACKGROUND:The role of endoscopic retrograde cholangiopancreatography (ERCP) in the management of acute pancreatitis has evolved over years since its introduction in 1968. Its importance in diagnosing the etiology of pancreatitis has steadily declined with the advent of less invasive diagnostic tools. The therapeutic implications of ERCP in acute pancreatitis are many fold and are directed towards management of known etiological factors or its related complications. This article highlights the current status of ERCP in acute pancreatitis. DATA SOURCES:An English literature search using PubMed database was conducted on ERCP in acute pancreatitis, the etiologies and complications of pancreatitis amenable to endotherapy and other related subjects, which were reviewed. RESULTS: ERCP serves as a primary therapeutic modality for management of biliary pancreatitis in speciifc situations, pancreatitis due to microlithiasis, speciifc types of sphincter of Oddi dysfunction, pancreas divisum, ascariasis and malignancy. In recurrent acute pancreatitis and smoldering pancreatitis it has a deifnite therapeutic utility. Complications of acute pancreatitis including pancreatic-duct disruptions or leaks, benign pancreatic-lfuid collections and pancreatic necrosis can be beneifcially dealt with. Intraductal ultrasound and pancreatoscopy during ERCP are useful in detecting pancreatic malignancy. CONCLUSIONS:The role of ERCP in acute pancreatitis is predominantly therapeutic and occasionally diagnostic. Its role in the management continues to evolve and advanced invasive procedures should be undertaken only in centers dedicated to pancreatic care.

  11. A comparison of glycemic control, water retention, and musculoskeletal effects of balaglitazone and pioglitazone in diet-induced obese rats

    DEFF Research Database (Denmark)

    Henriksen, Kim; Byrjalsen, Inger; Nielsen, Rasmus H

    2009-01-01

    : vehicle, pioglitazone 10 mg/kg, pioglitazone 30 mg/kg, balaglitazone 5 mg/kg, balaglitazone 10 mg/kg. At day -7, 21 and 42 fasting serum samples were collected and whole body tissue composition was evaluated by MR scanning. Food intake and bodyweights were monitored during the study period. At day 42...... of equipotent glucose lowering concentrations of the partial PPARgamma agonist balaglitazone and the full agonist pioglitazone in male diet-induced obese rats, to investigate effects on bone formation, fluid retention and fat accumulation. Sixty male dio induced obese rats were divided into five categories...

  12. Plasma osteoprotegerin is associated with testosterone levels but unaffected by pioglitazone treatment in patients with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, D; Hermann, Pernille; Rasmussen, Lars Melholt;

    2013-01-01

    Objective Increased osteoprotegerin (OPG) levels are associated with increased cardiovascular risk and decreased bone resorption. Pioglitazone treatment reduces the inflammatory state but may decrease bone mineral density. OPG levels during pioglitazone treatment have not previously been evaluated...... in polycystic ovary syndrome (PCOS). Research design and methods Plasma OPG levels were measured in 30 PCOS patients before and after randomized treatment with 30 mg pioglitazone/placebo for 16 weeks. Fourteen age and BMI matched healthy women were included as controls. Clinical and hormonal evaluations...

  13. Chronic pancreatitis: A surgical disease? Role of the Frey procedure

    Institute of Scientific and Technical Information of China (English)

    Alexra; Roch; Jérome; Teyssedou; Didier; Mutter; Jacques; Marescaux; Patrick; Pessaux

    2014-01-01

    Although medical treatment and endoscopic interven-tions are primarily offered to patients with chronic pancreatitis, approximately 40% to 75% will ultimately require surgery during the course of their disease. Al-though pancreaticoduodenectomy has been considered the standard surgical procedure because of its favorable results on pain control, its high postoperative complica-tion and pancreatic exocrine or/and endocrine dysfunc-tion rates have led to a growing enthusiasm for duodenal preserving pancreatic head resection. The aim of this review is to better understand the rationale underlying of the Frey procedure in chronic pancreatitis and to ana-lyze its outcome. Because of its hybrid nature, combin-ing both resection and drainage, the Frey procedure has been conceptualized based on the pathophysiology of chronic pancreatitis. The short and long-term outcome, especially pain relief and quality of life, are better after the Frey procedure than after any other surgical proce-dure performed for chronic pancreatitis.

  14. PPAR-γ agonist pioglitazone affects rat gouty arthritis by regulating cytokines.

    Science.gov (United States)

    Wang, R-C; Jiang, D-M

    2014-08-28

    The objective was to study peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone regulation effect and its mechanism of expression of cytokines on acute gouty arthritis synovial in rats. Rats with unilateral ankle were injected with artificial monosodium urate (MSU) crystals to make the acute gouty arthritis model. Taking the synovium 48 h after the injection of MSU and using RT-PCR, we assessed the effect of pioglitazone (20 mg·kg(-1)·day(-1), oral administration) on synovial expression, by detecting tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interferon-γ (IFN-γ). The pioglitazone treatment group showed synovial expression of TNF-α, and IFN-γ was significantly lower than in the control group; the inhibition rates were 78.5 and 60.4%. The IL-1 expression difference was not statistically significant between the two groups. Pioglitazone has anti-inflammatory effects on acute gouty arthritis by inhibiting the expression of TNF-α and IFN-γ.

  15. Pioglitazone treatment restores in vivo muscle oxidative capacity in a rat model of diabetes

    NARCIS (Netherlands)

    Wessels, B.; Ciapaite, J.; van den Broek, N. M. A.; Houten, S. M.; Nicolay, K.; Prompers, J. J.

    2015-01-01

    Aim: To determine the effect of pioglitazone treatment on in vivo and ex vivo muscle mitochondrial function in a rat model of diabetes. Methods: Both the lean, healthy rats and the obese, diabetic rats are Zucker Diabetic Fatty (ZDF) rats. The homozygous fa/fa ZDF rats are obese and diabetic. The he

  16. Effect of pioglitazone on the abrogated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart

    Directory of Open Access Journals (Sweden)

    Dhiraj Mittal

    2016-01-01

    Conclusion: Cardioprotective effect of IPC gets lost in hyperlipidemic rat heart. The results suggest that perfusion of pioglitazone restored the cardioprotective effect of IPC in hyperlipidemic rat heart, an effect that may be via PI3K and mTOR.

  17. Efficacy and safety of colesevelam in combination with pioglitazone in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Rosenstock, J; Truitt, K E; Baz-Hecht, M; Ford, D M; Tao, B; Chou, H S

    2014-12-01

    Colesevelam improves glycemic control in patients with type 2 diabetes when added to existing metformin-, sulfonylurea-, or insulin-based regimens. We evaluated colesevelam's effects in subjects on stable pioglitazone-based therapy. This 24-week multicenter, double-blind, randomized, placebo-controlled study enrolled adults with type 2 diabetes who had suboptimal glycemic control [HbA1c ≥ 58 mmol/mol (7.5%) and ≤ 80 mmol/mol (9.5%)] on pioglitazone (30 or 45 mg) with or without 1-2 other oral antidiabetes medications. Subjects were randomized to colesevelam 3.8 g/day (n = 280) or placebo (n = 282) added to existing pioglitazone-based therapy. Primary efficacy variable was mean change in HbA1c from baseline to Week 24. Secondary variables included safety and tolerability, fasting plasma glucose changes, glycemic responses, and lipid profile. Tertiary variables included lipid particle profile changes by nuclear magnetic resonance. Colesevelam decreased HbA1c [least-squares mean treatment difference, - 3.5 mmol/mol (- 0.32%); p diabetes inadequately controlled with pioglitazone-based therapy, add-on colesevelam therapy improved glycemic control and lipid parameters and was well tolerated. ClinicalTrials.gov identifier: NCT00789750.

  18. Digital preservation

    CERN Document Server

    Deegan, Marilyn

    2013-01-01

    Digital preservation is an issue of huge importance to the library and information profession right now. With the widescale adoption of the internet and the rise of the world wide web, the world has been overwhelmed by digital information. Digital data is being produced on a massive scale by individuals and institutions: some of it is born, lives and dies only in digital form, and it is the potential death of this data, with its impact on the preservation of culture, that is the concern of this book. So how can information professionals try to remedy this? Digital preservation is a complex iss

  19. Ligands for peroxisome proliferator-activated receptor gamma inhibit growth of pancreatic cancers both in vitro and in vivo.

    Science.gov (United States)

    Itami, A; Watanabe, G; Shimada, Y; Hashimoto, Y; Kawamura, J; Kato, M; Hosotani, R; Imamura, M

    2001-11-01

    Peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed largely in adipose tissues and plays an important role in adipocyte differentiation. Several studies have recently shown that ligands of PPARgamma could lead to growth inhibition in some malignancies. In our study, we focused on pancreatic cancers, because the prognosis of advanced pancreatic cancer has not significantly improved due to its resistance to various chemotherapeutic regimens, so that a novel strategy should be required. We show here that PPARgamma is expressed in 5 pancreatic cancer cell lines detected in both mRNA and protein level as well as in human primary and metastatic pancreatic carcinomas examined by immunohistochemical studies. A specific ligand of PPARgamma, troglitazone, led to G1 accumulation with the increase in p27(Kip1), but not p21(Waf1/Cip1) and inhibited cellular proliferation in a pancreatic cancer cell line, Panc-1. The overexpression of PPARgamma in a pancreatic cancer cell line, KMP-3, caused lipid accumulation, which suggested cell growth in some cancers might be inhibited, at least in part, through terminal differentiation in the adipogenic lineage. In addition, implanted Panc-1 tumors in nude mice showed significant inhibition of tumor growth, when treated with pioglitazone, another specific ligand of PPARgamma. Our results suggest that ligands of PPARgamma may be a novel therapeutic agent for the treatment of pancreatic carcinomas.

  20. Groove Pancreatitis: A Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Vallath Balakrishnan

    2007-09-01

    Full Text Available Context Groove pancreatitis is a rare type of segmental pancreatitis characterized by fibrous scars of the anatomic space between the dorsocranial part of the head of the pancreas, the duodenum, and the common bile duct. Case report A 40-year-old man, with a past history of chronic alcohol consumption presented with epigastric pain radiating to the back and intermittent vomiting and a weight loss of 9 kg. A CT of the abdomen revealed swelling of the pancreatic head, a hypodense mass and duodenal wall thickening with luminal narrowing. Peripancreatic fluid and dense strands were also seen. Upper gastrointestinal endoscopy revealed an edematous, shiny, reddish raised mucosa having a polypoid appearance with narrowing of the second portion of the duodenum. Histological examination of the duodenal biopsy specimens showed preservation of the crypt-villus ratio, and the submucosa showed Brunner gland hyperplasia. These findings appeared consistent with the diagnosis of groove pancreatitis. Presently, the patient is on conservative medical management with analgesics, proton pump inhibitors and a pancreatic enzyme supplement. Conclusions Groove pancreatitis often masquerades as pancreatic head carcinoma. This condition should be kept in mind when making the differential diagnosis between pancreatic masses and duodenal stenosis. In all cases of focal pancreatitis involving the head or uncinate process of the pancreas with involvement of the adjacent duodenum, the possibility of groove pancreatitis should be considered.

  1. Pioglitazone attenuates cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy.

    Science.gov (United States)

    Elrashidy, Rania A; Asker, Mervat E; Mohamed, Hoda E

    2012-09-01

    Pioglitazone has been demonstrated to have beneficial effects on cardiovascular outcomes. However, little is known about its effect on cardiac remodeling associated with diabetic nephropathy. Therefore, this study was designed to study the effects of pioglitazone on cardiac fibrosis and hypertrophy in a rat model of diabetic nephropathy. For this purpose, male Wistar albino rats were randomly assigned into 4 groups (n = 10 per group): normal (N) group, diabetic (D) group, diabetic nephropathic (DN) group received an equal amount of vehicle (0.5% carboxy methyl cellulose), and diabetic nephropathic group treated by oral administration of pioglitazone (10 mg/kg per d) for 4 weeks. Diabetic nephropathy was induced by subtotal nephrectomy plus streptozotocin (STZ) injection. The results revealed that DN rats showed excessive deposition of collagen fibers in their cardiac tissue, along with a marked myocyte hypertrophy. This was associated with a dramatic upregulation of cardiac transforming growth factor-β1 (TGF-β1) gene. Furthermore, the gene expression of matrix metalloproteinase 2 (MMP-2) decreased, while the gene expression of tissue inhibitor of metalloproteinase 2 (TIMP-2) increased in the hearts of DN rats. In addition, enhanced lipid peroxidation and myocardial injury, evidenced by a significant increase in their serum creatine kinase-MB level were observed in DN rats. All these abnormalities were ameliorated by pioglitazone administration. Our findings suggest that upregulation of cardiac TGF-β1 gene along with the imbalance between MMP-2 and TIMP-2 expressions is critically involved in cardiac fibrosis associated with diabetic nephropathy. Pioglitazone can ameliorate cardiac remodeling by suppressing the gene expression of TGF-β1 and regulating the MMP-2/TIMP-2 system.

  2. Evaluation of exposure to pioglitazone and risk of prostate cancer: a nested case–control study

    Science.gov (United States)

    Boxall, Naomi; Bennett, Dimitri; Hunger, Matthias; Dolin, Paul; Thompson, Paula L

    2016-01-01

    Objectives Investigate potential association between pioglitazone exposure and risk of prostate cancer. Research design and methods Nested, matched case–control study. UK primary care data (Clinical Practice Research Datalink (CPRD) GOLD) linked to inpatient (Hospital Episode Statistics (HES)) and cancer registry (National Cancer Information Network (NCIN)) data. English men aged ≥40 years diagnosed with type 2 diabetes mellitus, January 1, 2001 to January 5, 2015. Cases, with prostate cancer diagnosis, matched with up to 4 controls by age, cohort entry date and region. ORs for association of exposure to pioglitazone to incident prostate cancer, adjusted for potential confounders. Results From a cohort of 47 772 men with 243 923 person-years follow-up, 756 definite cases of prostate cancer were identified. Incidence was 309.9/100 000 person-years (95% CI 288.6 to 332.8). Pioglitazone use was not associated with prostate cancer risk; adjusted OR 0.759, 95% CI 0.502 to 1.148. Analyses showed no difference when possible cases, prostate cancer in CPRD GOLD only, included (adjusted OR 0.726, 95% CI 0.510 to 1.034). No association when adjusted for channeling bias (OR 0.778, 95% CI 0.511 to 1.184) or limited to an index date prior to July 1, 2011 (adjusted OR 0.508, 95% CI 0.294 to 0.879), despite prostate-specific antigen screening occurring more frequently among cases than controls (81.6% of 756 definite cases cf. 24.2% of 2942 controls (ppioglitazone use, increasing pioglitazone dose or increasing time since initiation. Conclusions In this real-world, nested matched case–control study, exposure to pioglitazone was not associated with increased risk of prostate cancer. PMID:28074141

  3. Comparison clinical and metabolic effects of metformin and pioglitazone in polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Karoon Shahebrahimi

    2016-01-01

    Full Text Available Introduction: Polycystic ovary syndrome (PCOS is one of the most common endocrine disorders in women. PCOS comprises a broad spectrum of anomalies, including hyperandrogenism, chronic anovulation, obesity, and infertility. Insulin resistance and its compensatory hyperinsulinemia play a key role in the pathogenicity of PCOS. This study compares the effects of 2 types of insulin sensitizer drugs, metformin and pioglitazone, on clinical, metabolic, and endocrine characteristics of women with PCOS. Methods: In this randomized clinical trial, 56 women with PCOS (ages 20–49 years were treated orally with either metformin (500 mg 3 times daily or pioglitazone (30 mg daily for 3 months. Clinical (body weight, blood pressure [BP], and body mass index and laboratory indices (fasting blood sugar [FBS], serum triglyceride [TG], cholesterol, low-density lipoprotein, high-density lipoprotein, insulin, testosterone, and dehydroepiandrosterone [DHEA] were measured before and after therapy. Data were analyzed by Chi-square and McNemar's tests. Results: Significant decreases were seen after treatment with metformin in extent of hair loss (P = 0.008, wrist circle (P = 0.011, weight (P = 0.047, diastolic BP (P = 0.023, and DHEA (P = 0.035. A significant decrease in TG was seen with pioglitazone treatment (P = 0.047. In both groups, significant decreases in acne, menstrual disturbance, FBS, and serum insulin were seen. Conclusion: There is a significant amelioration of endocrine and metabolic indices with pioglitazone in PCOS patients. Although we were not able to recommend one treatment regime over the other, pioglitazone offers a useful, alternate treatment in women with PCOS who are not able to tolerate metformin.

  4. Comparison clinical and metabolic effects of metformin and pioglitazone in polycystic ovary syndrome

    Science.gov (United States)

    Shahebrahimi, Karoon; Jalilian, Nasrin; Bazgir, Nasrin; Rezaei, Mansour

    2016-01-01

    Introduction: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. PCOS comprises a broad spectrum of anomalies, including hyperandrogenism, chronic anovulation, obesity, and infertility. Insulin resistance and its compensatory hyperinsulinemia play a key role in the pathogenicity of PCOS. This study compares the effects of 2 types of insulin sensitizer drugs, metformin and pioglitazone, on clinical, metabolic, and endocrine characteristics of women with PCOS. Methods: In this randomized clinical trial, 56 women with PCOS (ages 20–49 years) were treated orally with either metformin (500 mg 3 times daily) or pioglitazone (30 mg daily) for 3 months. Clinical (body weight, blood pressure [BP], and body mass index) and laboratory indices (fasting blood sugar [FBS], serum triglyceride [TG], cholesterol, low-density lipoprotein, high-density lipoprotein, insulin, testosterone, and dehydroepiandrosterone [DHEA]) were measured before and after therapy. Data were analyzed by Chi-square and McNemar's tests. Results: Significant decreases were seen after treatment with metformin in extent of hair loss (P = 0.008), wrist circle (P = 0.011), weight (P = 0.047), diastolic BP (P = 0.023), and DHEA (P = 0.035). A significant decrease in TG was seen with pioglitazone treatment (P = 0.047). In both groups, significant decreases in acne, menstrual disturbance, FBS, and serum insulin were seen. Conclusion: There is a significant amelioration of endocrine and metabolic indices with pioglitazone in PCOS patients. Although we were not able to recommend one treatment regime over the other, pioglitazone offers a useful, alternate treatment in women with PCOS who are not able to tolerate metformin. PMID:27867884

  5. Ultrasonographic diagnosis of pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Kyung; Park, Young Hee; Kim, Soo Mi; Ko, Young Tae; Lim, Jae Hoon; Kim, Soon Yong [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1985-04-15

    A retrospective analysis of ultrasonograms of 24 patients with acute pancreatitis and 8 patients with chronic pancreatitis was performed. Nine cases were proven by surgery and 23 cases were diagnosed clinically. Generalized pancreatic enlargement with normal or decreased echogenecity was principal findings in acute pancreatitis, while pancreas was normal in size and echogenecity was normal or slightly altered in chronic pancreatitis. Ultrasonography is considered a simple and accurate method in the diagnosis of acute pancreatitis and thus it could be an initial test in patients with suspected acute pancreatitis.

  6. Pancreatic islet transplantation

    Directory of Open Access Journals (Sweden)

    Corrêa-Giannella Maria

    2009-09-01

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

  7. Protective Effect of Melatonin on Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Jolanta Jaworek

    2012-01-01

    Full Text Available Melatonin, a product of the pineal gland, is released from the gut mucosa in response to food ingestion. Specific receptors for melatonin have been detected in many gastrointestinal tissues including the pancreas. Melatonin as well as its precursor, L-tryptophan, attenuates the severity of acute pancreatitis and protects the pancreatic tissue from the damage caused by acute inflammation. The beneficial effect of melatonin on acute pancreatitis, which has been reported in many experimental studies and supported by clinical observations, is related to: (1 enhancement of antioxidant defense of the pancreatic tissue, through direct scavenging of toxic radical oxygen (ROS and nitrogen (RNS species, (2 preservation of the activity of antioxidant enzymes; such as superoxide dismutase (SOD, catalase (CAT, or glutathione peroxidase (GPx, (3 the decline of pro-inflammatory cytokine tumor necrosis α (TNFα production, accompanied by stimulation of an anti-inflammatory IL-10, (4 improvement of pancreatic blood flow and decrease of neutrophil infiltration, (5 reduction of apoptosis and necrosis in the inflamed pancreatic tissue, (6 increased production of chaperon protein (HSP60, and (7 promotion of regenerative process in the pancreas. Conclusion. Endogenous melatonin produced from L-tryptophan could be one of the native mechanisms protecting the pancreas from acute damage and accelerating regeneration of this gland. The beneficial effects of melatonin shown in experimental studies suggest that melatonin ought to be employed in the clinical trials as a supportive therapy in acute pancreatitis and could be used in people at high risk for acute pancreatitis to prevent the development of pancreatic inflammation.

  8. Complications of pancreatic surgery

    Directory of Open Access Journals (Sweden)

    Åke Andrén-Sandberg

    2011-01-01

    Full Text Available Many diseases, including pancreatitis benign tumors and cancer, may require pancreas surgery. Pancreatic resection can lead to a prolonged survival in pancreatic cancer and even a potential chance for cure. However, the pancreatic surgery can result in complications, and high postoperative morbidity rates are still presence. This article reviews the pancreatic abstracts of American Pancreas Club 2011, which involves the more common complications, their prevention and treatment.

  9. Diabetes and pancreatic cancer

    OpenAIRE

    Christine Hsu; Muhammad Wasif Saif

    2012-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. Risk factors for pancreatic cancer are smoking, family history, chronic pancreatitis, and diabetes. There is controversy with regards to the causal relationship between diabetes and pancreatic cancer because many patients with pancreatic cancer have new onset diabetes. Abstracts presented at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting highlighted and supported the positive association ...

  10. Pancreatic transplantation

    Directory of Open Access Journals (Sweden)

    Åke Andrén-Sandberg

    2010-01-01

    Full Text Available A pancreas transplant is a surgical procedure to place a healthy pancreas from a donor into a patient whose pancreas no longer functions properly. Exocrine pancreas transplantation remains the standard treatment of choice for patients with diabetes mellitus complicated by end-stage renal disease. The use of pancreas transplantation for type 2 diabetes mellitus is an emerging concept. A pancreas transplant is often done in conjunction with a kidney transplant. Even if pancreas transplantation provides the best glycemic control option for diabetes mellitus, it is associated with significant morbidities related to infectious disease. The present article provides with a review of pancreatic transplantation.

  11. Toll-like Receptor 4 Signaling Pathway in the Protective Effect of Pioglitazone on Experimental Immunoglobulin A Nephropathy

    Directory of Open Access Journals (Sweden)

    Jia-Nan Zou

    2017-01-01

    Conclusions: Our study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.

  12. Pancreatic cancer risk in hereditary pancreatitis

    Directory of Open Access Journals (Sweden)

    Frank Ulrich Weiss

    2014-02-01

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

  13. Free carnitine and acylcarnitines in obese patients with polycystic ovary syndrome and effects of pioglitazone treatment

    DEFF Research Database (Denmark)

    Vigerust, Natalya Filipchuk; Bohov, Pavol; Bjørndal, Bodil;

    2012-01-01

    To determine fasting and insulin-stimulated levels of carnitine precursors, total and free carnitine, and acylcarnitines, and evaluate the impact of pioglitazone treatment in obese patients with polycystic ovary syndrome (PCOS).......To determine fasting and insulin-stimulated levels of carnitine precursors, total and free carnitine, and acylcarnitines, and evaluate the impact of pioglitazone treatment in obese patients with polycystic ovary syndrome (PCOS)....

  14. Pioglitazone is an effective treatment for patients with post-stroke depression combined with type 2 diabetes mellitus.

    Science.gov (United States)

    Hu, Yaozhi; Xing, Haiyan; Dong, Xiaomeng; Lu, Wenxian; Xiao, Xinxing; Gao, Lilin; Cui, Minghu; Chen, Jinbo

    2015-09-01

    The antidepressive effects of the antidiabetic medicine, pioglitazone, were recently reported in several studies. These effects may ameliorate the depressive symptoms of patients with post-stroke depression (PSD). The present study aimed to evaluate the antidepressive effect of pioglitazone in patients with PSD combined with type 2 diabetes. A total of 118 consecutive patients with stroke who had depression were studied for an average of 3 months. The Diagnostic and Statistical Manual of Mental Disorders (fourth edition) was used to assess whether a patient was depressed or not. The severity of depression was evaluated by the Hamilton depression rating scale (HAMD). In accordance with their HAMD scores, the 118 patients were divided into a severe depression group (n=40) and a mild and moderate (MM) depression group (n=78). These subjects were then divided into pioglitazone [30 mg once daily (qd)] and metformin (0.5 g twice daily) subgroups. All patients were given fluoxetine (20 mg qd). Follow-up evaluations, which included HAMD scores, activities of daily living (ADL) scores, fasting blood glucose (FBG) levels and fasting insulin (FINS) levels, were conducted on the first and third month following the beginning of the treatment. In the MM depression group, the HAMD score in the pioglitazone subgroup was lower than that in the metformin subgroup following treatment for 1 or 3 months. In the severe depression group, the HAMD score in the pioglitazone subgroup was lower than that in the metformin subgroup following 3 months of treatment. The FINS levels of the pioglitazone subgroup gradually decreased in the 3 months of treatment. No noticeable improvement was observed in the ADL scores and FBG values. In conclusion, the results of the current study demonstrate that pioglitazone effectively decreased HAMD scores and FINS values in patients with PSD, suggesting that pioglitazone may be useful for the treatment of patients with PSD combined with type 2 diabetes.

  15. SURGICAL TREATMENT OF PAIN IN CHRONIC PANCREATITIS:STUDIES OF 111 PATIENTS

    Institute of Scientific and Technical Information of China (English)

    D. Guinier; P. Mathieu; B. Heyd; G. Mantion

    2004-01-01

    Objective Evaluation of the efficacy of pancreatic resections for the treatment of chronic pains during chronic pancreatitis. Methods Retrospective study of inpatients for chronic pancreatitis between 1982 to 2000. Purpose of admission, morphological changes, treatments and results were evaluated. Results 142 patients were admitted for chronic pancreatitis. 111 patients suffered from chronic pains, due to morphological changes such as pseudocysts, inflammatory masses in the head, dilated pancreatic ducts, biliary or duodenal compressions. Denervations were never efficient, pancreatic resections achieved relief of pain in up to 75% of cases and drainages were efficient in 52% of cases. Conclusions Pancreatic resections during chronic pancreatitis seem to be the most efficient treatment of chronic pains. New techniques such as duodenum-preserving head resection or total pancreatectomy with islet autotransplantation should improve these results.

  16. Pioglitazone protects against cisplatin induced nephrotoxicity in rats and potentiates its anticancer activity against human renal adenocarcinoma cell lines.

    Science.gov (United States)

    Mahmoud, Mona F; El Shazly, Shimaa M

    2013-01-01

    Cisplatin-induced nephrotoxicity is a serious problem that limits its use in cancer treatment. The present study aimed to investigate the renal protective capacity of pioglitazone to reduce the cisplatin- induced nephrotoxicity. The underlying suggested mechanism(s) and whether this nephroprotective effect (if any) interferes with the cytotoxic effect of cisplatin on cancer cells were also investigated. Pioglitazone, Bisphenol A diglycidyl ether, BADGE, IP injected (Peroxisome proliferator- activated receptor gamma (PPAR-γ) antagonist), or their combination were administered to rats one hour before cisplatin injection. Moreover, their effects on the cell viability of human renal adenocarcinoma cell models (ACHN) were studied. The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB) genes expression in cisplatin injected rats. It increased both renal reduced glutathione (GSH) content and PPAR-γ gene expression. In contrast to the data obtained by prior administration of BADGE. Pioglitazone also potentiated the cytotoxic effect of cisplatin on human renal adenocarcinoma cells and this effect was abolished by BADGE co administration. In conclusion, these results suggested that pioglitazone protected against cisplatin- induced nephrotoxicity through its interaction with PPAR-γ receptors and antioxidant effects. Furthermore, pioglitazone did not interfere but rather potentiated the cytotoxic effects of cisplatin on human renal adenocarcinoma cells.

  17. Effect of Chronic Pioglitazone Treatment on Hepatic Gene Expression Profile in Obese C57BL/6J Mice.

    Science.gov (United States)

    Jia, Chunming; Huan, Yi; Liu, Shuainan; Hou, Shaocong; Sun, Sujuan; Li, Caina; Liu, Quan; Jiang, Qian; Wang, Yue; Shen, Zhufang

    2015-05-29

    Pioglitazone, a selective ligand of peroxisome proliferator-activated receptor gamma (PPARγ), is an insulin sensitizer drug that is being used in a number of insulin-resistant conditions, including non-alcoholic fatty liver disease (NAFLD). However, there is a discrepancy between preclinical and clinical data in the literature and the benefits of pioglitazone treatment as well as the precise mechanism of action remain unclear. In the present study, we determined the effect of chronic pioglitazone treatment on hepatic gene expression profile in diet-induced obesity (DIO) C57BL/6J mice in order to understand the mechanisms of NAFLD induced by PPARγ agonists. DIO mice were treated with pioglitazone (25 mg/kg/day) for 38 days, the gene expression profile in liver was evaluated using Affymetrix Mouse GeneChip 1.0 ST array. Pioglitazone treatment resulted in exacerbated hepatic steatosis and increased hepatic triglyceride and free fatty acids concentrations, though significantly increased the glucose infusion rate in hyperinsulinemic-euglycemic clamp test. The differentially expressed genes in liver of pioglitazone treated vs. untreated mice include 260 upregulated and 86 downregulated genes. Gene Ontology based enrichment analysis suggests that inflammation response is transcriptionally downregulated, while lipid metabolism is transcriptionally upregulated. This may underlie the observed aggravating liver steatosis and ameliorated systemic insulin resistance in DIO mice.

  18. The influence of nicotine on pioglitazone encapsulation into carbon nanotube: the investigation of molecular dynamic and density functional theory.

    Science.gov (United States)

    Zaboli, Maryam; Raissi, Heidar

    2017-02-01

    In this work, molecular dynamics simulations of the insertion of pioglitazone into the nanotube with chirality (10, 10) at 400 K and 1 bar in the presence and absence of nicotine molecules and in different drug concentrations have been studied. The main aim is consideration of the effect of nicotine in the drug encapsulation process. The results indicate that encapsulation of pioglitazone could be attributed to the water flow via van der Waals and hydrophilic interactions. Because of the existence of the partial π-π interactions between aromatic rings of pioglitazone and the conjugated aromatic rings of nanotube, pioglitazone molecule can enter inside the nanotube. Some physical properties such as hydrogen bonding, number of contacts, also, the diffusion coefficient of the pioglitazone and water molecules, and variation of the center of mass have been calculated during the simulation. Furthermore, computing the electronic structure has also been done on model systems for quantitative determination of the adsorption energy (Eads). The B3LYP/6-31G* level calculations on four different configurations of pioglitazone/carbon nanotube (CNT) and nicotine/CNT show that the interaction of drug with the inside of the nanotube is stronger than the other forms.

  19. [Obesity and pancreatic diseases].

    Science.gov (United States)

    Kim, Ho Gak; Han, Jimin

    2012-01-01

    Obesity is defined as BMI (calculated as weight in kg divided by height in m2) more than 30, and overweight is defined as BMI of 25-29.9. Obesity has been considered as a risk factor for pancreatic diseases, including pancreatitis and pancreatic cancer. Severe acute pancreatitis is significantly more frequent in obese patients. Furthermore, obese patients develop systemic and local complications of acute pancreatitis more frequently. The underlying mechanisms are increased inflammation and necrosis from increased amount of intra- and peri-pancreatic fat. In addition, obesity is a poor prognostic factor in acute pancreatitis, and overweight before disease onset appears to be a risk factor for chronic pancreatitis. Overweight and/or obesity are associated with greater risk of pancreatic cancer and younger age of onset. Physical activity appears to decrease the risk of pancreatic cancer, especially among those who are overweight. Long-standing diabetes increases the risk of pancreatic cancer. The pathogenic mechanism is that obesity and physical inactivity increase insulin resistance. In a state of hypersinulinemia, increased circulating level of insulin-like growth factor-1 induces cellular proliferation of pancreatic cancer. Obesity is associated with negative prognostic factor and increased mortality in pancreatic cancer. However, there are controversies regarding the effects of obesity on long-term post-operative results in the patient with pancreatic cancer.

  20. Pioglitazone is equally effective for diabetes prevention in older versus younger adults with impaired glucose tolerance.

    Science.gov (United States)

    Espinoza, Sara E; Wang, Chen-Pin; Tripathy, Devjit; Clement, Stephen C; Schwenke, Dawn C; Banerji, Mary Ann; Bray, George A; Buchanan, Thomas A; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Stentz, Frankie B; Reaven, Peter D; DeFronzo, Ralph A; Musi, Nicolas

    2016-12-01

    To determine the efficacy of pioglitazone to prevent type 2 diabetes in older compared to younger adults with pre-diabetes. Six hundred two participants with impaired glucose tolerance (IGT) were randomized in double blind fashion to placebo or pioglitazone for diabetes prevention in the ACT NOW study (NEJM 364:1104-1115, 2011). Cox proportional hazard regression was used to compare time to development of diabetes over a mean of 2 years between older (≥61 years) and younger participants. We compared effects of pioglitazone versus placebo on metabolic profiles, inflammatory markers, adipokines, β cell function (disposition index), insulin sensitivity (Matsuda index), and body composition by ANOVA. Diabetes incidence was reduced by 85 % in older and 69 % in younger subjects (p = 0.41). β cell function (disposition index) increased by 35.0 % in the older and 26.7 % in younger subjects (p = 0.83). Insulin sensitivity (Matsuda index) increased by 3.07 (5.2-fold) in older and by 2.54 (3.8-fold) in younger participants (p = 0.58). Pioglitazone more effectively increased adiponectin in older versus younger subjects (22.9 ± 3.2 μg/mL [2.7-fold] vs. 12.7 ± 1.4 μg/mL [2.2-fold], respectively; p = 0.04). Younger subjects tended to have a greater increase in whole body fat mass compared to older subjects (3.6 vs. 3.1 kg; p = 0.061). Younger and older subjects had similar decreases in bone mineral density (0.018 ± 0.0071 vs. 0.0138 ± 0.021 g/cm(2)). Younger and older pre-diabetic adults taking pioglitazone had similar reductions in conversion to diabetes and older adults had similar or greater improvements in metabolic risk factors, demonstrating that pioglitazone is useful in preventing diabetes in older adults.

  1. Imaging of Acute Pancreatitis.

    Science.gov (United States)

    Thoeni, Ruedi F

    2015-11-01

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

  2. Pancreatic Pseudocyst Pleural Fistula in Gallstone Pancreatitis

    Directory of Open Access Journals (Sweden)

    Sala Abdalla

    2016-01-01

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

  3. Pioglitazone and bladder cancer in human studies: is it diabetes itself, diabetes drugs, flawed analyses or different ethnicities?

    Science.gov (United States)

    Tseng, Chin-Hsiao

    2012-03-01

    This article reviews human observations on pioglitazone and bladder cancer risk. The PROspective pioglitAzone Clinical Trial In macroVascular Events trial showed an imbalance in bladder cancer between users of pioglitazone and placebo (14 versus six cases, p = 0.069). However, after excluding bladder cancer probably ascribed to other etiology, a blind assessment concluded that the imbalance might not be related to pioglitazone. Epidemiologic studies conducted in the United States and France using insurance databases independently suggested that pioglitazone use for >2 years might confer a 20%-40% higher risk. Another study evaluating bladder cancer risk in diabetic patients using the National Health Insurance in Taiwan did not find any incident bladder cancer case among 422 pioglitazone users for a follow-up of up to 3 years. Because observational studies may suffer from selection and information bias, and inadequate adjustment for confounders may inflate the estimated risk, causal inference from these studies should be interpreted with caution. While investigating cancer risk associated with a medication, indication bias should also be attended, especially when the medication is used at a late stage of the disease. Because pioglitazone is usually a second or third line antidiabetic agent, the users are always characterized by older age, longer diabetes duration, poorer glycemic control, and higher rates of complications and comorbidities. Biased estimates will also result if these differences are not appropriately addressed in the analyses. Current evidence neither concludes nor excludes a causal role of pioglitazone on bladder cancer. Clinical trials aiming at evaluating the risk of cancer associated with a medication is not ethical and may not be expected to provide an answer on the issue of pioglitazone-related bladder cancer. However, a meta-analysis using all available clinical trials to compare the bladder cancer risk between pioglitazone and comparators

  4. Digital Preservation.

    Science.gov (United States)

    Yakel, Elizabeth

    2001-01-01

    Reviews research on digital preservation issues, including born-digital and digitally recreated documents. Discusses electronic records research; metadata and other standards; electronic mail; Web-based documents; moving images media; selection of materials for digitization, including primary sources; administrative issues; media stability…

  5. RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF SEXAGLIPTIN AND PIOGLITAZONE IN TABLETS

    Directory of Open Access Journals (Sweden)

    M.Sarat

    2012-05-01

    Full Text Available A simple, selective, accurate high Performance Liquid Chromatographic (HPLC method was developed and validated for the analysis of Sexagliptin and Pioglitazone. Chromatographic separation achieved isocratically on a C18 column [Use Inertsil C18, 5m , 150 mm x 4.6 mm] utilizing a mobile phase of acetonitrile/phosphate buffer (60:40, v/v, pH 7.0 at a flow rate of 0.8 ml/min with UV detection at 260nm.Aceclofenac was used as an internal standard. The retention time of Sexagliptin, pioglitazone and aceclofenac was 2.48, 4.45 and 6.34 min respectively. The developed method was validated in terms of accuracy, precision, linearity, limit of detection, limit of quantitation.This study aimed at developing and validating an HPLC method, being simple, accurate and selective, and the proposed method can be used for the estimation of these drugs in combined dosage forms.

  6. [Insulin sensitizer--anti-diabetic drugs, metformin and pioglitazone that can improve insulin resistance].

    Science.gov (United States)

    Korenaga, Masaaki; Kawaguchi, Koutaro; Korenaga, Keiko; Uchida, Kouichi; Sakaida, Iso

    2006-06-01

    Nonalcoholic steatohepatitis (NASH), which is considered the hepatic manifestation of the metabolic syndrome is an increasingly cause of chronic liver disease in Japan. NASH is finally lead to liver cirrhosis and hepatocellular carcinoma as viral hepatitis, therefore, medical treatment should be considered, when NASH occurs. Treatment of patients with metabolic syndrome has been focused on the management of associated conditions such as obesity, hyperlipidemia, hypertension and hyperinsulinemia. Insulin resistance, that could accelerate liver inflammation and fibrosis by up-regulation of TNFa seems to be most important factor in many cases of NASH. The insulin-sensitizing drugs, which were biguanides (metformin) and thiazolidinediones (pioglitazone) have been shown to correct not only insulin resistance but also steatosis and inflammation in the liver. Metformin and pioglitazone might be useful drugs against NASH, however further investigations were needed.

  7. Pioglitazone could induce remission in major depression: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Colle R

    2016-12-01

    Full Text Available Romain Colle,1,* Delphine de Larminat,1,* Samuel Rotenberg,1 Franz Hozer,1 Patrick Hardy,1 Céline Verstuyft,2 Bruno Fève,3,* Emmanuelle Corruble1,* 1Psychiatry Department, Hôpital Bicêtre, INSERM, UMR S1178, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France; 2Molecular Genetic, Pharmacogenetics and Hormonology Department, Hôpital Bicêtre, INSERM UMR_S1184, Centre IMVA, University Paris-Sud, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France; 3Endocrinology Department, INSERM UMR_S938, Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire ICAN, Sorbonne Universités, Université Pierre et Marie Curie, Assistance Publique des Hôpitaux de Paris, Paris, France *These authors contributed equally to this work Background: Pioglitazone, a selective agonist of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ, prescribed for the treatment of type 2 diabetes, could have antidepressant properties. However, its potential to induce remission of major depressive episodes, the optimal clinical target for an antidepressant drug, is a matter of concern. Indeed, only one out of four double-blind randomized controlled trials show higher remission rates with pioglitazone than with control treatments. Hence, the main aim of this study was to perform a meta-analysis of the efficacy of pioglitazone for the treatment of MDE, focusing on remission rates.Methods: Four double-blind randomized controlled trials, comprising 161 patients with an MDE, were included in this meta-analysis. Pioglitazone was studied either alone (one study or as add-on therapy to conventional treatments (antidepressant drugs or lithium salts. It was compared either to placebo (three studies or to metformin (one study. Remission was defined by a Hamilton Depression Rating Scale score <8 after treatment.Results: Pioglitazone could induce higher remission

  8. Pioglitazone enhances mitochondrial biogenesis and ribosomal protein biosynthesis in skeletal muscle in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Skov, Vibe; Glintborg, Dorte; Knudsen, Steen

    2008-01-01

    Insulin resistance is a common metabolic abnormality in women with PCOS and leads to an elevated risk of type 2 diabetes. Studies have shown that thiazolidinediones (TZDs) improve metabolic disturbances in PCOS patients. We hypothesized that the effect of TZDs in PCOS is, in part, mediated...... by changes in the transcriptional profile of muscle favoring insulin sensitivity. Using Affymetrix microarrays, we examined the effect of pioglitazone (30 mg/day for 16 weeks) on gene expression in skeletal muscle of 10 obese women with PCOS metabolically characterized by a euglycemic-hyperinsulinemic clamp....... Moreover, we explored gene expression changes between these PCOS patients before treatment and 13 healthy women. Treatment with pioglitazone improved insulin-stimulated glucose metabolism and plasma adiponectin, and reduced fasting serum insulin (all P

  9. Pioglitazone, quercetin and hydroxy citric acid effect on hepatic biomarkers in Non Alcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Krishna Mohan Surapaneni

    2014-01-01

    Full Text Available Background: Non alcoholic steatohepatitis (NASH, severe form of diseases belonging to the spectrum of the Non alcoholic fatty liver disease (NAFLD. It is an asymptomatic disease which leads to fibrosis and finally to cirrhosis, an end stage liver disease. Objective: To study the effect of pioglitazone, quercetin and hydroxy citric acid on hepatic biomarkers and various biochemical parameters in experimentally induced non alcoholic steatohepatitis (NASH. Materials and Methods: Male Wister rats were divided into 8 groups. The activities of alkaline phosphatase (ALP, aspartate transaminase (AST, alanine transaminase (ALT, lactate dehydrogenase (LDH and γ-Glutamyl Transferase (GGT were assayed in serum. The levels of various other biochemical parameters such as serum albumin, total bilirubin, creatinine, urea, uric acid and glucose were also estimated in experimental NASH. Results: The NASH group produced severe liver injury by significantly increasing the serum levels of ALT, AST, GGT and LDH compared with that of the control. However, the experimental NASH rats treated with pioglitazone, with quercetin and with hydroxy citric acid showed an obvious decrease in ALT, AST, GGT and LDH levels when compared with that of NASH induced group. A significant increase in the levels of albumin, creatinine, urea, uric acid, glucose and total bilirubin was noticed in experimentally induced NASH group (group 2 when compared to rats in control group (group 1. Conclusion: It could be inferred from this study that, pioglitazone, quercetin and hydroxy citric acid may afford protection to the liver against NASH, as evidenced by the results of this study on the levels of various biochemical parameters such as glucose, urea, uric acid, creatinine and bilirubin. Whereas from the results of hepatic marker enzymes, it is evident that optimal protection was observed after quercetin treatment against experimental NASH whereas pioglitazone and hydroxy citric acid also

  10. Formulation and Evaluation of Multilayered Tablets of Pioglitazone Hydrochloride and Metformin Hydrochloride

    Directory of Open Access Journals (Sweden)

    Y. Ankamma Chowdary

    2014-01-01

    Full Text Available In the treatment of type 2 diabetes mellitus a continuous therapy is required which is a more complex one. As in these patients there may be a defect in both insulin secretion and insulin action exists. Hence, the treatment depends on the pathophysiology and the disease state. In the present study, multilayered tablets of pioglitazone hydrochloride 15 mg and metformin hydrochloride 500 mg were prepared in an attempt for combination therapy for the treatment of type 2 diabetes mellitus. Pioglitazone HCl was formulated as immediate release layer to show immediate action by direct compression method using combination of superdisintegrants, namely, crospovidone and avicel PH 102. Crospovidone at 20% concentration showed good drug release profile at 2 hrs. Metformin HCl was formulated as controlled release layer to prolong the drug action by incorporating hydrophilic polymers such as HPMC K4M by direct compression method and guar gum by wet granulation method in order to sustain the drug release from the tablets and maintain its integrity so as to provide a suitable formulation. The multilayered tablets were prepared after carrying out the optimization of immediate release layer and were evaluated for various precompression and postcompression parameters. Formulation F13 showed 99.97% of pioglitazone release at 2 hrs in 0.1 N HCl and metformin showed 98.81% drug release at 10 hrs of dissolution in 6.8 pH phosphate buffer. The developed formulation is equivalent to innovator product in view of in vitro drug release profile. The results of all these evaluation tests are within the standards. The procedure followed for the formulation of these tablets was found to be reproducible and all the formulations were stable after accelerated stability studies. Hence, multilayered tablets of pioglitazone HCl and metformin HCl can be a better alternative way to conventional dosage forms.

  11. Protective effect of pioglitazone, a PPARγ agonist against acetaminophen-induced hepatotoxicity in rats.

    Science.gov (United States)

    Gupta, Gaurav; Krishna, Gopala; Chellappan, Dinesh Kumar; Gubbiyappa, Kumar Shiva; Candasamy, Mayuren; Dua, Kamal

    2014-08-01

    Acetaminophen has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity and even acute liver failure when taken at an overdose. Pioglitazone, PPARγ ligand, is clinically tested and used in treatment of diabetes. PPARγ is a key nuclear hormone receptor of lipid metabolisms and regulates several gene transcriptions associated with differentiation, growth arrest, and apoptosis. The aim of our study was to evaluate the hepatoprotective activity of pioglitazone on acetaminophen-induced hepatotoxicity and to understand the relationship between the PPARγ and acetaminophen-induced hepato injury. For the experiment, Sprague-Dawley rats (160-180 g) were used and divided into four groups. Groups I and II were normal and experimental controls, respectively. Groups III and IV received the pioglitazone 20 mg/kg for 10 days. Hepatotoxicity was induced in Groups II and III on the eighth day with acetaminophen (i.p. 350 mg/kg body weight). The hepatoprotective effect was evaluated by performing an assay of the total protein, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and α-fetoprotein as well as glutathione peroxidase, lipid peroxidation, catalase, superoxide dismutase, and glutathione transferase and liver histopathology. The assay results were presented as mean and standard error of mean for each group. The study group was compared with the control group by one-way ANOVA test. A p value of hepatotoxicity. Liver histopathological examination showed that pioglitazone administration antagonized acetaminophen -induced liver pathological damage. Various biochemical estimations of different hepatic markers and antioxidant enzymes and histopathological studies of liver tissues glimpse a support to its significant hepatoprotective activity on acetaminophen -induced hepatotoxicity.

  12. Pioglitazone administration alters ovarian gene expression in aging obese lethal yellow mice

    Directory of Open Access Journals (Sweden)

    Weber Mitch

    2008-03-01

    Full Text Available Abstract Background Women with polycystic ovary syndrome (PCOS are often treated with insulin-sensitizing agents, e.g. thiazolidinediones (TZD, which have been shown to reduce androgen levels and improved ovulatory function. Acting via peroxisome proliferator-activated receptor (PPAR gamma, TZD alter the expression of a large variety of genes. Lethal yellow (LY; C57BL/6J Ay/a mice, possessing a mutation (Ay in the agouti gene locus, exhibit progressive obesity, reproductive dysfunction, and altered metabolic regulation similar to women with PCOS. The current study was designed to test the hypothesis that prolonged treatment of aging LY mice with the TZD, pioglitazone, alters the ovarian expression of genes that may impact reproduction. Methods Female LY mice received daily oral doses of either 0.01 mg pioglitazone (n = 4 or an equal volume of vehicle (DMSO; n = 4 for 8 weeks. At the end of treatment, ovaries were removed and DNA microarrays were used to analyze differential gene expression. Results Twenty-seven genes showed at least a two-fold difference in ovarian expression with pioglitazone treatment. These included leptin, angiopoietin, angiopoietin-like 4, Foxa3, PGE1 receptor, resistin-like molecule-alpha (RELM, and actin-related protein 6 homolog (ARP6. For most altered genes, pioglitazone changed levels of expression to those seen in untreated C57BL/6J(a/a non-mutant lean mice. Conclusion TZD administration may influence ovarian function via numerous diverse mechanisms that may or may not be directly related to insulin/IGF signaling.

  13. Effects of pioglitazone on expressions of matrix metalloproteinases 2 and 9 in kidneys of diabetic rats

    Institute of Scientific and Technical Information of China (English)

    董凤芹; 李红; 蔡卫民; 陶君; 李群; 阮昱; 郑芬萍; 张哲

    2004-01-01

    Background The changes in matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions were examined in the kidneys of diabetic rats to investigate the degradative pathway of collagen type Ⅳ (C-Ⅳ) and the protective effects of pioglitazone on an experimental model of diabetic nephropathy.Methods In 54 SD rats used in our study, 18 served as normal controls. Diabetes mellitus was induced in 36 age- and weight-matched rats by intraperitoneal injection of streptozotocin (70 mg/kg); 18 of the diabetic rats were allocated at random to receive pioglitazone (20 mg*kg-1*d-1) in their drinking water and 18 served as diabetic controls. Rats were killed after 2, 4, or 8 weeks of treatment. Kidneys were examined pathomorphologically and the expressions of MMP-2, MMP-9, and C-Ⅳ were analyzed by immunohistochemistry, and the results were quantified by image analysis techniques.Results Diabetes mellitus was associated with a decrease in the expression of MMP-2 in the glomeruli (P0.05, vs control). The expression of MMP-9 did not show any change when comparing the three groups (P>0.05, vs control). STZ-diabetic rats were also associated with an increase in the expression of C-Ⅳ in the glomeruli and the interstitium (P<0.05, vs control). All diabetes-associated changes in MMP-2 expression were attenuated by pioglitazone treatment in association with reduced C-Ⅳ accumulation. Conclusions These results indicate that a decrease in MMP-2 expression in the glomeruli of diabetic rats may lead to impairment of C-Ⅳ degradation and contribute to the matrix accumulation in diabetic nephropathy. Pioglitazone treatment, which can attenuate the decrease of glomerular MMP-2 and the increase of C-Ⅳ degradation, has curative effects on diabetic nephropathy.

  14. DEVELOPMENT AND EVALUATION OF MICROBALLOONS OF PIOGLITAZONE HYDROCHLORIDE USING EUDRAGIT S-100

    OpenAIRE

    Nishant S. Gandhi et al.

    2012-01-01

    ABSTRACTKeywords:Pioglitazone hydrochloride,Eudragit S-100,Solvent diffusion evaporation,Floating microspheres,Polymer: Drug ratioCorrespondence to Author:Nishant GandhiOld Power House Road, Ramnagar, Gondia, Maharashtra, IndiaVarious approaches have been used to retain the dosage form in the stomach as a way of increasing the gastric residence time (GRT), including floatation systems; high-density systems; mucoadhesive systems; magnetic systems; unfoldable, extendible, or swellable systems;...

  15. PROactive 07: pioglitazone in the treatment of type 2 diabetes: results of the PROactive study

    Directory of Open Access Journals (Sweden)

    Erl

    2007-09-01

    Full Text Available Erland Erdmann1, John Dormandy2, Robert Wilcox3, Massimo Massi-Benedetti4, Bernard Charbonnel51University of Cologne, Cologne, Germany; 2Department of Clinical Vascular Research, St Georges Hospital, London, UK; 3Department of Cardiovascular Medicine, Queen’s Medical Centre, University Hospital, Nottingham, UK; 4University of Perugia, Medicine and Metabolic Diseases, Perugia, Italy; 5Clinique d’Endocrinologie, Hôtel Dieu, Nantes Cedex 1, FranceAbstract: Patients with type 2 diabetes face an increased risk of macrovascular disease compared to those without. Significant reductions in the risk of major cardiovascular events can be achieved with appropriate drug therapy, although patients with type 2 diabetes remain at increased risk compared with non-diabetics. The thiazolidinedione, pioglitazone, is known to offer multiple, potentially antiatherogenic, effects that may have a beneficial impact on macrovascular outcomes, including long-term improvements in insulin resistance (associated with an increased rate of atherosclerosis and improvement in the atherogenic lipid triad (low HDL-cholesterol, raised triglycerides, and a preponderance of small, dense LDL particles that is observed in patients with type 2 diabetes. The recent PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive study showed that pioglitazone can reduce the risk of secondary macrovascular events in a high-risk patient population with type 2 diabetes and established macrovascular disease. Here, we summarize the key results from the PROactive study and place them in context with other recent outcome trials in type 2 diabetes.Keywords: pioglitazone, macrovascular disease, type 2 diabetes, secondary prevention

  16. Pioglitazone alleviates cardiac and vascular remodelling and improves survival in monocrotaline induced pulmonary arterial hypertension.

    Science.gov (United States)

    Behringer, Arnica; Trappiel, Manuela; Berghausen, Eva Maria; Ten Freyhaus, Henrik; Wellnhofer, Ernst; Odenthal, Margarete; Blaschke, Florian; Er, Fikret; Gassanov, Natig; Rosenkranz, Stephan; Baldus, Stephan; Kappert, Kai; Caglayan, Evren

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

  17. Is Pancreatic Cancer Hereditary?

    Science.gov (United States)

    ... gene testing for hereditary pancreatitis is now available. Ataxia telangiectasia The team at Johns Hopkins discovered that inherited ... are known to cause the clinical syndrome of "ataxia telangiectasia," and 2-3% of people with familial pancreatic ...

  18. Pancreatitis-imaging approach

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  19. Pancreatitis - series (image)

    Science.gov (United States)

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

  20. Additive Renoprotection by Pioglitazone and Fenofibrate against Inflammatory, Oxidative and Apoptotic Manifestations of Cisplatin Nephrotoxicity: Modulation by PPARs.

    Science.gov (United States)

    Helmy, Mai M; Helmy, Maged W; El-Mas, Mahmoud M

    2015-01-01

    Nephrotoxicity is a major side effect for the antineoplastic drug cisplatin. Here, we employed pharmacological, biochemical, and molecular studies to investigate the role of peroxisome proliferator-activated receptors (PPARs) in cisplatin nephrotoxicity. Rats were treated with a single i.p. dose of cisplatin (5 mg/kg) alone or combined with pioglitazone (PPARγ agonist), fenofibrate (PPARα agonist), pioglitazone plus fenofibrate, or thalidomide (Tumor necrosis factor-α inhibitor; TNF-α). Cisplatin nephrotoxicity was evidenced by rises in renal indices of functional (blood urea nitrogen, BUN, and creatinine), inflammatory (TNF-α, interleukin 6, IL-6), oxidative (increased malondialdehyde, MDA, and decreased superoxide dismutase, SOD and nitric oxide metabolites, NOx), apoptotic (caspase 3), and histological (glomerular atrophy, acute tubular necrosis and vacuolation) profiles. Cisplatin effects were partly abolished upon concurrent exposure to pioglitazone, fenofibrate, or thalidomide; more renoprotection was observed in rats treated with pioglitazaone plus fenofibrate. Immunostaining showed that renal expressions of PPARα and PPARγ were reduced by cisplatin and restored to vehicle-treated values after simultaneous treatment with pioglitazone or fenofibrate. Fenofibrate or pioglitazone renoprotection remained unaltered after concurrent blockade of PPARα (GW6471) and PPARγ (GW9662), respectively. To complement the rat studies, we also report that in human embryonic kidney cells (HEK293 cells), increases caused by cisplatin in inflammatory, apoptotic, and oxidative biomarkers were (i) partly improved after exposure to pioglitazone, fenofibrate, or thalidomide, and (ii) completely disappeared in cells treated with a combination of all three drugs. These data establish that the combined use of pioglitazone and fenofibrate additively improved manifestations of cisplatin nephrotoxicity through perhaps GW6471/GW9662-insensitive mechanisms.

  1. FORMULATION AND EVALUATION OF MUCOADHESIVE MICROSPHERES OF PIOGLITAZONE HYDROCHLORIDE USING A NATURAL POLYMER

    Directory of Open Access Journals (Sweden)

    Mobeen Mohd.

    2015-04-01

    Full Text Available The objective of the present investigation was to design a controlled release dosage form for a thiazolidinedione oral hypoglycemic drug i.e., pioglitazone hydrochloride employing a natural polymer. The present study was also aimed to increase the biological half-life by developing it in the form of sustained release microspheres. The present study aimed at employing a natural polymer in formulating the mucoadhesive microspheres and estimate its effect over the controlled release of the drug from the formulation. The microspheres of pioglitazone hydrochloride were prepared by employing sodium alginate as a cell forming polymer and by using a natural bio-adhesive polymer viz. goru gum in the ratios of 1:1, 1:1.5 and 1:2, by orifice ion gelation method with varying concentrations of calcium chloride. Six batches of microspheres (MS1 – MS6 were prepared. The microspheres were evaluated for various micromeritic properties and it was observed that all the batches exhibited free-flowing properties. Scanning electron microscopy results showed that the microspheres were almost spherical in shape and discrete. The FTIR results showed that there were no interactions between the drug and the excipients. The in vitro release profile indicated that all the batches of microspheres showed controlled and prolonged drug release over an extended period, with acceptable release kinetics. The work demonstrated that among all the formulations of microspheres, the microspheres of the formulation MS4 are promising candidates for the sustained release of pioglitazone hydrochloride.

  2. Pioglitazone halts axonal degeneration in a mouse model of X-linked adrenoleukodystrophy.

    Science.gov (United States)

    Morató, Laia; Galino, Jorge; Ruiz, Montserrat; Calingasan, Noel Ylagan; Starkov, Anatoly A; Dumont, Magali; Naudí, Alba; Martínez, Juan José; Aubourg, Patrick; Portero-Otín, Manuel; Pamplona, Reinald; Galea, Elena; Beal, M Flint; Ferrer, Isidre; Fourcade, Stéphane; Pujol, Aurora

    2013-08-01

    X-linked adrenoleukodystrophy is a neurometabolic disorder caused by inactivation of the peroxisomal ABCD1 transporter of very long-chain fatty acids. In mice, ABCD1 loss causes late onset axonal degeneration in the spinal cord in association with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. Increasing evidence indicates that oxidative stress and bioenergetic failure play major roles in the pathogenesis of X-linked adrenoleukodystrophy. In this study, we aimed to evaluate whether mitochondrial biogenesis is affected in X-linked adrenoleukodystrophy. We demonstrated that Abcd1 null mice show reduced mitochondrial DNA concomitant with downregulation of mitochondrial biogenesis pathway driven by PGC-1α/PPARγ and reduced expression of mitochondrial proteins cytochrome c, NDUFB8 and VDAC. Moreover, we show that the oral administration of pioglitazone, an agonist of PPARγ, restored mitochondrial content and expression of master regulators of biogenesis, neutralized oxidative damage to proteins and DNA, and reversed bioenergetic failure in terms of ATP levels, NAD+/NADH ratios, pyruvate kinase and glutathione reductase activities. Most importantly, the treatment halted locomotor disability and axonal damage in X-linked adrenoleukodystrophy mice. These results lend support to the use of pioglitazone in clinical trials with patients with adrenomyeloneuropathy and reveal novel molecular mechanisms of action of pioglitazone in neurodegeneration. Future studies should address the effects of this anti-diabetic drug on other axonopathies in which oxidative stress and mitochondrial dysfunction are contributing factors.

  3. Safety profiling of pioglitazone and telmisartan combination by sub-chronic toxicity study in rat.

    Science.gov (United States)

    Sengupta, Pinaki; Das, Arindam; Ibrahim, Fuzianna; Mandal, Uttam Kumar; Chatterjee, Bappaditya; Mahmood, Syed; Das, Sreemoy Kanti; Kifayatullah, Muhammad

    2016-11-01

    It has been reported that the major cause of mortality in diabetes is cardiovascular diseases and contribution of hypertension is significant in this context. Pioglitazone, a thiazolidinedione class of therapeutic agent is used to treat type 2 diabetes mellitus. Telmisartan, an angiotensin receptor blocker antihypertensive has been reported to have beneficial effect if co-administered with pioglitazone for the management of diabetes complications. The present research work aims to evaluate the safety/toxicity profile of this combination in rat model. The investigation was carried out after co-administering the drugs to the rats for 28 days at three dose levels of 50, 100 and 150 mg/kg covering low to high dose ranges. Various hematological and biochemical parameters were studied in addition to the histopathology of the major organs in order to evaluate the toxicity profile of the combination. Absence of mortality and histopathological changes as well as unaltered hematological and biochemical parameters was observed. This preliminary investigation concludes that the combination of pioglitazone and telmisartan can primarily be stated as safe in animals, even at the dose level which is several folds higher than the intended human dose. Thus, this combination can be explored in future to develop a rational therapy regimen to treat hypertensive diabetic patients.

  4. Pathogenic mechanisms of pancreatitis

    Science.gov (United States)

    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

  5. Experimental Models of Pancreatitis

    OpenAIRE

    Hyun, Jong Jin; Lee, Hong Sik

    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 character...

  6. Autoimmune pancreatitis: A review

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Autoimmune pancreatitis has emerged over the last 40 years from a proposed concept to a well established and recognized entity. As an efficient mimicker of pancreatic carcinoma, its early and appropriate recognition are crucial. With mounting understanding of its pathogenesis and natural history, significant advances have been made in the diagnosis of autoimmune pancreatitis. The characteristic laboratory features and imaging seen in autoimmune pancreatitis are reviewed along with some of the proposed diagnostic criteria and treatment algorithms.

  7. Epidemiology of pancreatic cancer

    OpenAIRE

    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 ...

  8. Intraoperative gastrojejunoscopy-assisted fistulojejunostomy for postoperative pancreatic fistula.

    Science.gov (United States)

    Toihata, Tasuku; Hashimoto, Daisuke; Hayashi, Hiromitsu; Chikamoto, Akira; Beppu, Toru; Baba, Hideo

    2014-11-01

    Postoperative pancreatic fistula is a known complication after pancreaticojejunostomy. When an anastomosis collapses completely, two-stage reconstruction is necessary. Herein, we describe the case of a 70-year-old woman who underwent subtotal stomach-preserving pancreaticoduodenectomy with pancreaticojejunostomy after she had developed a severe postoperative pancreatic fistula. The pancreaticojejunostomy was divided, and an external pancreatic drainage tube was placed. Four months later, fistulojejunostomy between the pancreas and the stump of the jejunum was performed successfully using intraoperative gastrojejunoscopy. © 2014 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.

  9. Preserving Chile

    OpenAIRE

    Brennand, Charlotte P.

    2010-01-01

    The best way to preserve chile depends on how you plan to use it and your available storage space. Frozen or canned chile is best for chile rellenos and salsas. Stews can use frozen, canned or dried chile. Dried chile has minimal storage requirements and is light-weight for taking on camping trips. Pickled chiles can be used on a relish plate or as an ingredient in other dishes.

  10. Recurrent pancreatitis secondary to pancreatic ascariasis.

    Science.gov (United States)

    Lee, K H; Shelat, V G; Low, H C; Ho, K Y; Diddapur, R K

    2009-06-01

    Ascaris lumbricoides infestations are endemic in tropical countries. Ascaris lumbricoides can occasionally cause biliary obstruction and result in obstructive jaundice or pancreatitis. We present a 34-year-old Bangladeshi woman with biliary ascariasis, resulting in recurrent pancreatitis. Her diagnosis was made with endoscopic retrograde cholangiopancreatography performed during an acute attack of pain.

  11. The effects of the PPAR-gamma gonist pioglitazone on plasma concentrations of circulating vasoactive factors in type II diabetes mellitus

    NARCIS (Netherlands)

    de Boer, R. A.; Martens, F. M. A. C.; Kuipers, I.; Boomsma, F.; Visseren, F. L. J.

    2010-01-01

    The use of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist pioglitazone, which is registered as an oral antidiabetic drug, has consistently been associated with a decrease in blood pressure (BP) of about 3-5 mm Hg. The present study evaluates the effects of pioglitazone tre

  12. Effect of pioglitazone on muscle sympathetic nerve activity in type 2 diabetes mellitus with α-glucosidase inhibitor.

    Science.gov (United States)

    Kobayashi, Daisuke; Takamura, Masayuki; Murai, Hisayoshi; Usui, Soichiro; Ikeda, Tatsunori; Inomata, Jun-ichiro; Takashima, Shin-ichiro; Kato, Takeshi; Furusho, Hiroshi; Takeshita, Yumie; Ota, Tsuguhito; Takamura, Toshinari; Kaneko, Shuichi

    2010-12-08

    Activation of the sympathetic nervous system is augmented in patients with type 2 diabetes mellitus (DM). Pioglitazone, an anti-diabetic drug, improves insulin resistance, but its influence on sympathetic nerve activity is not clear. To identify the relationship between insulin resistance and sympathetic activity, we examined muscle sympathetic nerve activity (MSNA) in controlled type 2 DM patients with alpha-glucosidase inhibitor (GI). We measured MSNA and calculated homeostasis model assessment of insulin resistance index (HOMA-IR) in twelve DM patients treated with alpha-GI and thirteen age-matched healthy subjects. In DM patients with alpha-GI, all parameters were reexamined after three months of treatment with pioglitazone. MSNA and HOMA-IR were significantly greater in DM patients with alpha-GI compared to healthy subjects. Hemoglobin A1c did not differ in DM patients before and after pioglitazone. However, pioglitazone significantly decreased MSNA in DM patients compared with alpha-GI (21.7±5.2 vs. 32.0±6.8 burst/min, ppioglitazone was similar to that in healthy subjects. HOMA-IR significantly decreased after pioglitazone, and a significant relationship was found between the absolute change in MSNA and HOMA-IR (r=0.65, ppioglitazone provides an additional effect on inhibition of sympathetic nerve activity.

  13. Pioglitazone suppresses advanced glycation end product-induced expression of plasminogen activator inhibitor-1 in vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Xiaochen Yuan; Naifeng Liu

    2011-01-01

    Advanced glycation end products (AGEs) play an important role in vascular complications of diabetes, including fibrinolytic abnormalities.Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARΥ) agonist, has recently been shown to reduce circulating plasminogen activator inhibitor-1 (PAI-1) levels in diabetes mellitus. In the present study, we investigated the effects of pioglitazone on the expression of local PAI-1 in rat vascular smooth muscle cells (VSMCs) induced by AGEs and the underlying mechanism. The result showed that AGEs could enhance the PAI-1 expression by 5.1-fold in mRNA and 2.7-fold in protein level, as evaluated by real-time RT-PCR and Western blotting,respectively. Pioglitazone was found to down-regulate the AGE-stimulated PAI-1 expression in VSMCs. However, these inhibitory effects were partially attenuated by the PPARΥ antagonist, GW9662. Furthermore, we found that AGEs induced a rapid increase in phosphorylation and activation of extracellular signal-regulated protein kinase 1/2 (ERK 1/2). The ERK kinase inhibitor, UO126, partially prevented the induction of PAI-1 by AGEs. Moreover, pioglitazone was also found to inhibit the phosphorylation of ERKi/2. Taken together, it was concluded that pioglitazone could inhibit AGE-induced PAI-1 expression, which was mediated by the ERK1/2 and PPARΥ pathways. Our findings suggestedpioglitazone had a therapeutic potential in improving fibrinolytic activity, and consequently preventing thromboembolic complications of diabetes and cardiovascular disease.

  14. Gender differences in non-glycemic responses to improved insulin sensitivity by pioglitazone treatment in patients with type 2 diabetes.

    Science.gov (United States)

    Arnetz, Lisa; Dorkhan, Mozhgan; Alvarsson, Michael; Brismar, Kerstin; Ekberg, Neda Rajamand

    2014-04-01

    Excess cortisol and GH induce insulin resistance, a central feature of type 2 diabetes (T2D). To study whether the insulin sensitizer pioglitazone affects basal cortisol levels and the GH-IGF-I axis in patients with T2D. Forty-eight patients with T2D (men/women = 28:20, age 61 ± 1 years, BMI 31 ± 0.6 kg/m(2)) were treated for 26 weeks with pioglitazone 30-45 mg daily in addition to their preexisting therapy. Insulin, proinsulin, HbA(1c), IGF-I, IGFBP-1, and basal cortisol were analyzed before and after treatment. Pioglitazone decreased proinsulin/insulin ratio and HbA(1c) decreased (HbA(1c) from 7.8 ± 0.2 to 6.6 ± 0.2% in men and from 7.6 ± 0.2 to 6.1 ± 0.2% in women, p pioglitazone increased IGF-I regardless of gender and in women also increased basal cortisol. Increased IGF-I may contribute to improved insulin sensitivity after treatment. There seems to be gender differences in treatment responses to pioglitazone on lipid metabolism and basal cortisol, perhaps correcting different mechanisms of insulin resistance between genders.

  15. Pancreatic pseudo-cyst.

    Directory of Open Access Journals (Sweden)

    José Raúl Sánchez Aguilar

    2005-12-01

    Full Text Available The pancreatic pseudocyst is the most common cystic lesion of the pancreas. It constitutes an amilasa rich liquid collection, located inside or adjacent to the pancreas; surrounded by a wall without ephithelium, as result of a sharp or chronic pancreatitis, pancreatic trauma, or obstruction of pancreatic conduit. 50 % solves spontaneously in 6 weeks, but some of they require surgical treatment. We presented the Good Clinical Practices Guideline for Pancreatic pseudocysts, approved by consent in the 3th National Good Clinical Practices Workshop in Pediatric Surgery (Camagüey, Cuba; February 23 – 26, 2004.

  16. Pancreatic Resections for Advanced M1-Pancreatic Carcinoma: The Value of Synchronous Metastasectomy

    Directory of Open Access Journals (Sweden)

    S. K. Seelig

    2010-01-01

    Materials and Methods. From January 1, 2004 to December, 2007 a total of 20 patients with pancreatic malignancies were retrospectively evaluated who underwent pancreatic surgery with synchronous resection of hepatic, adjacent organ, or peritoneal metastases for proven UICC stage IV periampullary cancer of the pancreas. Perioperative as well as clinicopathological parameters were evaluated. Results. There were 20 patients (9 men, 11 women; mean age 58 years identified. The primary tumor was located in the pancreatic head (n=9, 45%, in pancreatic tail (n=9, 45%, and in the papilla Vateri (n=2, 10%. Metastases were located in the liver (n=14, 70%, peritoneum (n=5, 25%, and omentum majus (n=2, 10%. Lymphnode metastases were present in 16 patients (80%. All patients received resection of their tumors together with metastasectomy. Pylorus preserving duodenopancreatectomy was performed in 8 patients, distal pancreatectomy in 8, duodenopancreatectomy in 2, and total pancreatectomy in 2. Morbidity was 45% and there was no perioperative mortality. Median postoperative survival was 10.7 months (2.6–37.7 months which was not significantly different from a matched-pair group of patients who underwent pancreatic resection for UICC adenocarcinoma of the pancreas (median survival 15.6 months; P=.1. Conclusion. Pancreatic resection for M1 periampullary cancer of the pancreas can be performed safely in well-selected patients. However, indication for surgery has to be made on an individual basis.

  17. Diabetes and Pancreatic Cancer

    Science.gov (United States)

    Li, Donghui

    2011-01-01

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

  18. Pancreatic Cancer Genetics.

    Science.gov (United States)

    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).

  19. Low dose pioglitazone does not affect bone formation and resorption markers or bone mineral density in streptozocin-induced diabetic rats.

    Science.gov (United States)

    Tsirella, E; Mavrakanas, T; Rager, O; Tsartsalis, S; Kallaras, K; Kokkas, B; Mironidou-Tzouveleki, M

    2012-04-01

    Our study aims to investigate the effect of a low-dose pioglitazone regimen on bone mineral density and bone formation-resorption markers in control and diabetic rats. Wistar rats were divided into 4 groups: non-diabetic controls, control rats receiving pioglitazone (3 mg/kg), streptozocin-treated diabetic rats (50 mg/kg), diabetic rats treated with pioglitazone (3 mg/kg). The duration of the experiment was 8 weeks. Diabetes in our rats was associated with weight loss, increased urinary calcium excretion and reduced plasma osteocalcin levels. Diabetes mellitus did not affect bone mineral density. Pioglitazone administration had no impact on bone formation and resorption markers levels and did not modify bone mineral density in the four studied groups. Pioglitazone at the 3 mg/kg dose was not associated with significant skeletal complications in our experimental model.

  20. Preservation Priority

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    China ratified the UNESCO Convention Concerning the Protection of World Cultural and Natural Heritage in 1985. This set the tone for a course of action aimed at protecting the common heritage of mankind in tandem with the international community. Recently, Chao Huashan, a renowned expert on world heritage studies in China, spoke to Beijing Review reporter Zan Jifang, sharing his understanding about the value of the World Heritage Convention and his suggestions for China’s future work on preserving its heritage. Excerpts follow:

  1. Pancreatitis in children.

    Science.gov (United States)

    Winchester, M

    1992-12-01

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

  2. Inherited pancreatic cancer syndromes.

    Science.gov (United States)

    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.

  3. Pancreatic Cancer Screening.

    Science.gov (United States)

    Das, Koushik K; Early, Dayna

    2017-09-06

    This review describes the rationale for pancreatic cancer screening, outlines groups that are at elevated risk for pancreatic cancer, and summarizes the relative risk in each setting. We also review the methods available for performing pancreatic cancer screening and the recommended screening intervals. Several genetic mutations have been identified that increase the risk for pancreatic cancer. Most are rare, however, and at-risk individuals are most often those with a strong family history of pancreatic cancer (with multiple family members affected) but no identifiable genetic mutation. Known genetic syndromes that increase the risk for pancreatic cancer include hereditary pancreatitis, familial atypical mole and multiple melanoma, Peutz-Jeghers syndrome, Lynch syndrome, BRCA mutations, and Li-Fraumeni syndrome. Genetic testing should be performed in conjunction with genetic counseling, and testing of an affected family member is preferred if possible.The goal of pancreatic cancer screening is to identify pancreatic cancer at an early, curable stage or, ideally, to identify precancerous lesions that can be resected to prevent the development of cancer. Imaging can be performed with either endoscopic ultrasound (EUS) or magnetic resonance cholangiopancreatography (MRCP). These techniques are generally considered to be complementary, although an advantage of EUS is that cysts or solid lesions can be sampled at the time of the procedure. Published results of small cohorts of high-risk patients in pancreatic cancer screening programs have demonstrated a high prevalence of small cystic lesions identified on EUS or MRCP, which often represent side-branch intraductal papillary mucinous neoplasms (IPMN). Knowledge of conditions and syndromes that increase pancreatic cancer risk allows one to identify those patients that may benefit from pancreatic cancer screening. As we gather evidence from large, international, multicenter cohorts of patients at high-risk for pancreatic

  4. Anti-pruritic activity of pioglitazone on serotonin-induced scratching in mice: possible involvement of PPAR-gamma receptor and nitric oxide.

    Science.gov (United States)

    Shafizadeh, Milad; Rajaba, Armin; Imran khan, Muhammad; Ostadhadi, Sattar; Rastegar, Hosein; Dehpour, Ahmadreza

    2014-12-05

    Pioglitazone is a member of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, particularly used in management of type II diabetes. However it also has effects in some dermatological disorders. The current study was designed to investigate the effects of oral administration of pioglitazone and the association of nitric oxide, in serotonin-induced scratching in mice. In order to produce the scratching activity, serotonin (141 nm/site) was administered intradermally in the nape of the neck. Pioglitazone in concentrations of 10, 20, 40 and 80 mg/kg, was peroral administered (p.o) as a single dose, 4 h before the serotonin injection. PPAR-γ antagonist, GW9662 (2 mg/kg, i.p); a non-specific nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1 mg/kg, i.p); or a nitric oxide precursor, L-arginine (100 mg/kg, i.p.); adminstrated 15 min before pioglitazone were analyzed for anti-scratching activity. Results obtained showed that pioglitazone (40 and 80 mg/kg, p.o) reduced the scratching in a dose-dependent manner. GW9662 inverted the anti-scratching effect of pioglitazone (80 mg/kg). Acute dose of L-NAME (1 mg/kg, i.p) also prevented the anti-scratching property of pioglitazone (80 mg/kg, p.o); although L-arginine was used in sub-effective dose (100 mg/kg, i.p), however it potentiated the anti-scratching behavior when co-injected with pioglitazone (20 mg/kg, p.o). The results indicate that acute pioglitazone has an anti-scratching effect on serotonin-induced scratching in mice. It is concluded that anti-scratching outcome of acute pioglitazone is initiated via activation of PPAR-γ receptor and to some extent by the NO pathway.

  5. Risk factors of pancreatic leakage after pancreaticoduodenectomy

    Institute of Scientific and Technical Information of China (English)

    Yin-Mo Yang; Xiao-Dong Tian; Yan Zhuang; Wei-Min Wang; Yuan-Lian Wan; Yan-Ting Huang

    2005-01-01

    AIM: To analyze the risk factors for pancreatic leakage after pancreaticoduodenectomy (PD) and to evaluate whether duct-to-mucosa pancreaticojejunostomy could reduce the risk of pancreatic leakage.METHODS: Sixty-two patients who underwent PD at our hospital between January 2000 and November 2003 were reviewed retrospectively. The primary diseases of the patients included pancreas cancer, ampullary cancer, bile duct cancer, islet cell cancer, duodenal cancer, chronic pancreatitis, pancreatic cystadenoma, and gastric cancer.Standard PD was performed for 25 cases, PD with extended lymphadenectomy for 27 cases, pylorus-preserving PD for 10 cases. A duct-to-mucosa pancreaticojejunostomy was performed for patients with a hard pancreas and a dilated pancreatic duct, and a traditional end-to-end invagination pancreaticojejunostomy for patients with a soft pancreas and a non-dilated duct. Patients were divided into two groups according to the incidence of postoperative pancreaticojejunal anastomotic leakage: 10 cases with leakage and 52 cases without leakage. Seven preoperative and six intraoperative risk factors with the potential to affect the incidence of pancreatic leakage were analyzed with SPSS10.0 software. Logistic regression was then used to determine the effect of multiple factors on pancreatic leakage.RESULTS: Of the 62 patients, 10 (16.13%) were identified as having pancreatic leakage after operation. Other major postoperative complications included delayed gastric emptying (eight patients), abdominal bleeding (four patients), abdominal abscess (three patients) and wound infection (two patients). The overall surgical morbidity was 43.5% (27/62). The hospital mortality in this series was 4.84% (3/62), and the mortality associated with pancreatic fistula was 10% (1/10). Sixteen cases underwent duct-to-mucosa pancreaticojejunostomy and 1 case (1/16, 6.25%) devel-oped postoperative pancreatic leakage, 46 cases underwent invagination pancreaticojejunostomy and 9

  6. DPP-4 inhibitors:study progress of the preservation of pancreatic β-cells%DPP-4抑制剂保护 β 细胞功能的作用

    Institute of Scientific and Technical Information of China (English)

    邹大进

    2012-01-01

    There is a progressive deterioration of β-cell function and mass in type 2 diabetes. DPP-4 inhibitor therapy started soon after diagnosis of type 2 diabetes could preserve and even reverse the progressive loss of insulin secretary capacity that is the fundamental cause of type 2 diabetes.%胰岛β细胞受损是T2DM发病的关键因素.β细胞受损包括分泌功能受损和数量减少.新诊断T2DM后及早使用DPP-4抑制剂可有效保护β细胞,甚至逆转β细胞分泌功能的丧失,延缓糖尿病病程进展.

  7. The peroxisome proliferator-activated receptor-γ agonist pioglitazone protects against cisplatin-induced renal damage in mice.

    Science.gov (United States)

    Jesse, Cristiano R; Bortolatto, Cristiani F; Wilhelm, Ethel A; Roman, Silvane Souza; Prigol, Marina; Nogueira, Cristina W

    2014-01-01

    Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against non-diabetic kidney disease in experimental models. Here, we investigated the effect of PPAR-γ agonist pioglitazone against acute renal injury on a cisplatin model in mice. Nephrotoxicity was induced by a single intraperitoneal (i.p.) injection of cisplatin (10 mg kg(-1)). Pioglitazone was administered for six consecutive days in doses of 15 or 30 mg kg(-1)  day(-1), per os (p.o.), starting 3 days before cisplatin injection. Cisplatin treatment to mice induced a marked renal failure, characterized by a significant increase in serum urea and creatinine levels and alterations in renal tissue architecture. Cisplatin exposure induced oxidative stress as indicated by decreased levels of non-enzymatic antioxidant defenses [glutathione (GSH) and ascorbic acid levels] and components of the enzymatic antioxidant defenses [superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx), glutathione reductase (GR) and and glutathione S-transferase(GST) activities)] in renal tissue. Administration of pioglitazone markedly protected against the increase in urea and creatinine levels and histological alterations in kidney induced by cisplatin treatment. Pioglitazone administration ameliorated GSH and ascorbic acid levels decreased by cisplatin exposure in mice. Pioglitazone protected against the inhibition of CAT, SOD, GPx, GR and GST activities induced by cisplatin in the kidneys of mice. These results indicated that pioglitazone has a protective effect against cisplatin-induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of PPAR-γ agonists in human application for protecting against drugs-induced nephrotoxicity.

  8. HPLC-DAD Method for the Pharmacokinetic Interaction Study of Atorvastatin with Pioglitazone and Cholestyramine in Wistar Rats.

    Science.gov (United States)

    Sharma, Ritesh N; Pancholi, Shyam S

    2014-01-01

    Carotid intima-media thickness is used as a surrogate marker for cardiovascular complications in diabetes mellitus. The combination of atorvastatin and pioglitazone was found to be effective in reducing the thickness of the carotid intima-media layer. The method of RP-HPLC coupled with a diode array detector (DAD) was developed for the pharmacokinetic interaction study of atorvastatin with pioglitazone and cholestyramine, respectively, in Wistar rats. Atorvastatin (ATR) and pioglitazone (PIO) were resolved on a C18 column with a mobile phase composed of 48% methanol, 19% acetonitrile, and 33% 10 mM ammonium formate (v/v/v; pH 3.5±0.3, by formic acid) and a 260 nm detection wavelength on the diode array detector. The method was validated according to international standards with good reproducibility and linear response; mean (r) 0.9987 and 0.9972 to ATR and PIO, respectively. The coefficients of variation of intra- and interassay precision ranged between 4.95-8.12 and 7.29-9.67, respectively. Pharmacokinetic parameters were determined in rats following an oral administration of atorvastatin in the presence and absence of pioglitazone and also with cholestyramine. Compared with the control given atorvastatin alone, the Cmax and AUC of atorvastatin were merely unchanged in rats with the co-administration of pioglitazone, while they decreased by nearly 21 and 15%, respectively, with the concurrent use of cholestyramine. There were no significant changes in Tmax and the plasma half-life (T1/2 ) of atorvastatin in both cases. The performed experiment demonstrated that the presented method was suitable for the estimation and pharmacokinetic interaction study of atorvastatin with pioglitazone and cholestyramine in Wistar rat plasma.

  9. Pioglitazone inhibits the expression of matrix metalloproteinase-9, a protein involved in diabetes-associated wound healing.

    Science.gov (United States)

    Zhang, Jun; Huang, Xiaoyuan; Wang, Lingfeng

    2014-08-01

    Matrix metalloproteinase-9 (MMP-9) is a protein involved in diabetes-associated wound healing. The present study aimed to determine whether pioglitazone, an agonist of peroxisome proliferator-activated receptor‑γ (PPAR-γ), inhibits the expression of MMP-9. HaCaT cells at a density of 6x105 cells/well were seeded into 6-well plates in medium and were cultured for 24 h. The cells were then treated with bovine serum albumin (BSA) only or advanced glycation end‑product (AGE)-BSA (50, 100, 200, 300 or 400 µg/ml), with or without pioglitazone (0.5 or 1 µM). The effects of AGE-BSA on cell viability were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The levels of MMP-9 secreted into the medium were detected by an enzyme-linked immunosorbent assay. The mRNA and protein levels were analyzed by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. AGEs are able to increase the level of MMP-9 mRNA in HaCaT cells and the levels of MMP-9 protein secreted into the medium. Pioglitazone (0.5 or 1 µΜ) significantly inhibited the levels of MMP-9 in the treated HaCaT cells. Pioglitazone (0.5 or 1 µΜ) also suppressed the levels of MMP-9 in the cell culture medium. Pioglitazone at concentrations of 0.5 and 1 µΜ significantly suppressed the levels of MMP-9 mRNA to 20 or 8%, respectively. These results suggest that pioglitazone is able to effectively suppress the expression of MMP-9 via a transcriptional mechanism.

  10. Pioglitazone ameliorates memory deficits in streptozotocin-induced diabetic mice by reducing brain β-amyloid through PPARY activation

    Institute of Scientific and Technical Information of China (English)

    Li-ping LIU; Tian-hua YAN; Li-ying JIANG; Wei HU; Meng HU; Chao WANG; Qian ZHANG

    2013-01-01

    Aim:To examine the effects of pioglitazone,a PPARY agonist,on memory performance and brain amyloidogenesis in streptozotocin (STZ)-induced diabetic mice.Methods:ICR male mice were injected with STZ (150 mg/kg,iv) to induce experimental diabetes.Pioglitazone (9 and 18 mg·kg1-d-1,po) was administered for 6 weeks.Passive avoidance and Morris water maze (MWM) tests were used to evaluate cognitive function.The blood glucose and serum insulin levels were detected using the glucose oxidase method and an ELISA assay,respectively.β-amyloid (Aβ),β-amyloid precursor protein (APP),β-amyloid precursor protein cleaving enzyme 1 (BACE1),NF-κB p65,the receptor for advanced glycation end products (RAGE) and PPARy in the brains were analyzed using Western blotting assays.Results:The STZ-induced diabetic mice characterized by hyperglycemia and hypoinsulinemia performed poorly in both the passive avoidance and MWM tests,accompanied by increased Aβ1-40/Aβ1-42,APP,BACE1,NF-κB p65 and RAGE levels and decreased PPARy level in the hippocampus and cortex.Chronic pioglitazone treatment significantly ameliorated the memory deficits of STZ-induced diabetic mice,and suppressed expression of APP,BACE1,RAGE and NF-κB p65,and activated PPARy in the hippocampus and cortex.However,pioglitazone did not significantly affect blood glucose and insulin levels.Conclusion:Pioglitazone ameliorates memory deficits in STZ-induced diabetic mice by reducing brain Aβ level via activation of PPARy,which is independent of its effects on blood glucose and insulin levels.The results suggest that pioglitazone may be used for treating the cognitive dysfunction in type 1 diabetes mellitus.

  11. Pancreatic Stellate Cells and Chronic Alcoholic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Raffaele Pezzilli

    2007-03-01

    Full Text Available Chronic pancreatitis is a disease often characterized by recurrent episodes of abdominal pain accompanied by progressive pancreatic exocrine and endocrine insufficiency [1] and it sometimes requires multiple hospitalizations. Obstructive jaundice, duodenal stenosis, left-sided portal hypertension, pseudocyst and mass formation, and pancreatic carcinoma may occur as complications of chronic pancreatitis. The disease is frequently the result of chronic alcohol abuse, even if other factors such as genetic alterations, autoimmune disorders, and obstructive disease of the biliary tract and the pancreas may cause the disease [2]. Medical therapy is the treatment of choice for most patients and it is based on substitutive therapy for either exocrine or endocrine insufficiency and on analgesics for pain control. In the presence of intractable pain, surgical management is the main option [3] even if, in recent years, other therapeutic options such as endoscopic therapy [4], thoracoscopic splanchnicectomy [5], and extracorporeal shockwave lithotripsy have been applied in clinical practice [6]. From a pathological point of view, chronic pancreatitis is characterized by irregular sclerosis with destruction and loss of the exocrine parenchyma, and complete replacement of acinar, ductal and endocrine tissue by fibrotic tissue. It has recently been reported that acute alcoholic pancreatitis develops in a pancreas already affected by chronic pancreatitis [7]. In 1982, Watari et al. [8] reported the presence of vitamin A-containing cells in the vitamin A-fed rat pancreas. These were later described and characterized as stellate cells in the rat and the human pancreas [9, 10]. Pancreatic stellate cells are morphologically similar to hepatic stellate cells. They bear long cytoplasmic processes and are situated close to the pancreatic acini. In the quiescent state, these cells contain lipid droplets, store vitamin A and express markers such as desmin, glial

  12. 胰十二指肠切除术与保留十二指肠胰头次全切除术治疗胰头肿块型慢性胰腺炎的临床疗效%Clinical efficacy of pancreaticoduodenectomy and duodenum-preserving pancreatic head resection for the treatment of chronic pancreatitis with mass in the head of the pancreas

    Institute of Scientific and Technical Information of China (English)

    贺舜民; 李志强; 余枭; 余灿; 朱红伟; 汪东文; 宋军

    2015-01-01

    Objective To investigate the clinical efficacy of pancreaticoduodenectomy (PD) and duodenumpreserving pancreatic head resection (DPPHR,including Beger,Frey and Berne procedures)for the treatment of chronic pancreatitis (CP) with mass in the head of the pancreas.Methods The clinical data of 48 patients with CP who were admitted to the Armed Police Corps Hospital of Hunan province(13) and the Third Xiangya Hospital of Central South University (35) between January 2007 and December 2013 were retrospectively analyzed.The operation methods were selected according to clinical symptoms,imaging findings and intraoperative pathological examinations.Twenty-three patients receiving PD (Whipple procedure or pylorus-preserving PD) were allocated into PD group and 25 receiving DPPHR (Beger,Frey and Berne procedures) were allocated into DPPHR group.The operation time,volume of intraoperative blood loss,rate of postoperative pain relief,changes of pancreatic endocrine and exocrine function,complications,duration of hospital stay and hospital expenses in the 2 groups were analyzed.Patients were followed up by telephone interview and outpatient examination up to September 2014.Measurement data with normal distribution were presented as (x) ± s.Comparison between groups was analyzed using the t test.Count data were analyzed using chi-square test or Fisher exact probability.Results Of the 23 patients in the PD group,15 patients received Whipple procedure and 8 patients received pylorus preserving PD.Of 25 patients in the DPPHR group,8 patients received Beger procedure,13 patients received Frey procedure and 4 patients received Berne procedure.The operation time and volume of intraoperative blood loss were (5.5 ± 0.4) hours,(372 ± 174) mL in the PD group,and (4.2 ± 0.6) hours,(272 ± 114) mL in the DPPHR group,showing significant differences between the 2 groups (t =8.712,2.375,P < 0.05).Three patients had massive hemorrhage in the PD group and 2 patients receiving Beger

  13. Data Preservation

    Directory of Open Access Journals (Sweden)

    Carlo Meghini

    2013-07-01

    Full Text Available Digital information is a vital resource in our knowledge economy, valuable for research and education, science and the humanities, creative and cultural activities, and public policy (The Blue Ribbon Task Force on Sustainable Digital Preservation and Access, 2010. New high-throughput instruments, telescopes, satellites, accelerators, supercomputers, sensor networks, and running simulations are generating massive amounts of data (Thanos, 2011. These data are used by decision makers for improving the quality of life of citizens. Moreover, researchers are employing sophisticated technologies to analyse these data to address questions that were unapproachable just a few years ago (Helbing & Balietti, 2011. Digital technologies have fostered a new world of research characterized by immense datasets, unprecedented levels of openness among researchers, and new connections among researchers, policy makers, and the public (The National Academy of Sciences, 2009.

  14. Power Preservation

    DEFF Research Database (Denmark)

    Galster, Kjeld

    Power Preservation (Abstract) In the 17th century, just as today, coalitions needed ‘lead nations’. This was assumed to be a power with great military and economic potentials, and Denmark endeavoured to act as such a leader in the Thirty Years War from 1626 to 28. The results were not encouraging...... in the military field and they were disastrous as far as fiscal matters were concerned. Sweden took over the leadership of the protestant side and she took over Denmark’s place amongst the great powers of the Baltic Region. From that time onwards, Danish influence and options on the international stage gradually...... declined. Thus, Denmark of the 17th century is not to be counted amongst the great powers, but since Christian V’s accession to the throne in 1670 Denmark-Norway has developed into one of Europe’s most highly militarised states. Apart from a permanently combat ready navy, the country maintains a standing...

  15. Pancreatic Panniculitis: A rare manifestation of Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Ronak Patel

    2015-05-01

    Full Text Available Context Pancreatic panniculitis is a very rare complication associated with pancreatic disease and perhaps even a presage to pancreatic pathology. Case report We present a case of pancreatic panniculitis in a 61 year old patient who was treated for sudden onset of abdominal pain associated with nausea and vomiting secondary to acute pancreatitis of unknown etiology. He subsequently developed skin lesions consistent with pancreatic panniculitis which gradually improved after resolution of his acute condition and treatment with topical steroid cream. Conclusion We discuss and review the literature along with highlighting for the readers the important clinical and histopathologic features of acute pancreatitis associated pancreatic panniculitis.

  16. Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients With Insulin Resistance Without Diabetes Mellitus.

    Science.gov (United States)

    Young, Lawrence H; Viscoli, Catherine M; Curtis, Jeptha P; Inzucchi, Silvio E; Schwartz, Gregory G; Lovejoy, Anne M; Furie, Karen L; Gorman, Mark J; Conwit, Robin; Abbott, J Dawn; Jacoby, Daniel L; Kolansky, Daniel M; Pfau, Steven E; Ling, Frederick S; Kernan, Walter N

    2017-05-16

    Insulin resistance is highly prevalent among patients with atherosclerosis and is associated with an increased risk for myocardial infarction (MI) and stroke. The IRIS trial (Insulin Resistance Intervention after Stroke) demonstrated that pioglitazone decreased the composite risk for fatal or nonfatal stroke and MI in patients with insulin resistance without diabetes mellitus, after a recent ischemic stroke or transient ischemic attack. The type and severity of cardiac events in this population and the impact of pioglitazone on these events have not been described. We performed a secondary analysis of the effects of pioglitazone, in comparison with placebo, on acute coronary syndromes (MI and unstable angina) among IRIS participants. All potential acute coronary syndrome episodes were adjudicated in a blinded fashion by an independent clinical events committee. The study cohort was composed of 3876 IRIS participants, mean age 63 years, 65% male, 89% white race, and 12% with a history of coronary artery disease. Over a median follow-up of 4.8 years, there were 225 acute coronary syndrome events, including 141 MIs and 84 episodes of unstable angina. The MIs included 28 (19%) with ST-segment elevation. The majority of MIs were type 1 (94, 65%), followed by type 2 (45, 32%). Serum troponin was 10× to 100× upper limit of normal in 49 (35%) and >100× upper limit of normal in 39 (28%). Pioglitazone reduced the risk of acute coronary syndrome (hazard ratio, 0.71; 95% confidence interval, 0.54-0.94; P=0.02). Pioglitazone also reduced the risk of type 1 MI (hazard ratio, 0.62; 95% confidence interval, 0.40-0.96; log-rank P=0.03), but not type 2 MI (hazard ratio, 1.05; 95% confidence interval, 0.58-1.91; P=0.87). Similarly, pioglitazone reduced the risk of large MIs with serum troponin >100× upper limit of normal (hazard ratio, 0.44; 95% confidence interval, 0.22-0.87; P=0.02), but not smaller MIs. Among patients with insulin resistance without diabetes mellitus

  17. Walled-off pancreatic necrosis

    Institute of Scientific and Technical Information of China (English)

    Michael; Stamatakos; Charikleia; Stefanaki; Konstantinos; Kontzoglou; Spyros; Stergiopoulos; Georgios; Giannopoulos; Michael; Safioleas

    2010-01-01

    Walled-off pancreatic necrosis (WOPN), formerly known as pancreatic abscess is a late complication of acute pancreatitis. It can be lethal, even though it is rare. This critical review provides an overview of the continually expanding knowledge about WOPN, by review of current data from references identified in Medline and PubMed, to September 2009, using key words, such as WOPN, infected pseudocyst, severe pancreatitis, pancreatic abscess, acute necrotizing pancreatitis (ANP), pancreas, inflammation and al...

  18. Formulation and development of self-microemulsifying drug delivery system of pioglitazone hydrochloride

    Directory of Open Access Journals (Sweden)

    Jyotsana R. Madan

    2014-01-01

    Full Text Available Self-microemulsifying drug delivery system (SMEDDS is a promising system for the Biopharmaceutics Classification System (BCS class II drugs. The current research aimed to improve the dissolution of poorly water-soluble antidiabetic drug pioglitazone HCl by formulating it in SMEDDS. Liquid SMEDDS of pioglitazone HCl were formulated with Capmul MCM C8 and oleic acid as oil phase, Cremophor RH 40 and Tween 80 as surfactant phase, and Transcutol P as cosurfactant phase after screening various vehicles. The prepared formulations were evaluated for self-emulsifying ability and phase diagram was constructed to optimize the system. These systems were further characterized for globule size, effect of pH and robustness, zeta potential, drug content, viscosity, self-emulsification time, polydispersity index, % transmittance, thermodynamic stability, surface morphology, and drug release. The system was robust to different pH media and dilution volumes. The optimized system possessed a mean globule size of 122.2 nm, zeta potential around -22.9 mV, drug content 99.66 ± 0.47%, viscosity 0.8874 ± 0.026 cP, emulsification time 38 s, polydispersity index value of 0.5, and transmittance value of 99.3 ± 0.6%. Drug release in hydrochloric acid buffer pH 2 was found to be 99.35 ± 0.38%. More than three-fold increase in dissolution characteristics of pioglitazone HCl in SMEDDS was observed as compared to pure and marketed formulation. Liquid SMEDDS filled in hard gelatin capsule (HGC shell was found to be compatible. Stability studies show there was no sign of phase separation or precipitation and no change in drug content was observed.

  19. Prevention of pancreatic cancer.

    Science.gov (United States)

    Kuroczycki-Saniutycz, Stefan; Grzeszczuk, Agnieszka; Zwierz, Zbigniew Wojciech; Kołodziejczyk, Paweł; Szczesiul, Jakub; Zalewska-Szajda, Beata; Ościłowicz, Krystyna; Waszkiewicz, Napoleon; Zwierz, Krzysztof; Szajda, Sławomir Dariusz

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDA) accounts for 95% of all pancreatic cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the lowest five-year survival rate as compared to others cancers. PDA in Poland is the fifth leading cause of death after lung, stomach, colon and breast cancer. In our paper we have analysed the newest epidemiological research, some of it controversial, to establish the best practical solution for pancreatic cancer prevention in the healthy population as well as treatment for patients already diagnosed with pancreatic cancer. We found that PDA occurs quite frequently but is usually diagnosed too late, at its advanced stage. Screening for PDA is not very well defined except in subgroups of high-risk individuals with genetic disorders or with chronic pancreatitis. We present convincing, probable, and suggestive risk factors associated with pancreatic cancer, many of which are modifiable and should be introduced and implemented in our society.

  20. Prevention of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Stefan Kuroczycki-Saniutycz

    2017-02-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDA accounts for 95% of all pancreatic cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the lowest five-year survival rate as compared to others cancers. PDA in Poland is the fifth leading cause of death after lung, stomach, colon and breast cancer. In our paper we have analysed the newest epidemiological research, some of it controversial, to establish the best practical solution for pancreatic cancer prevention in the healthy population as well as treatment for patients already diagnosed with pancreatic cancer. We found that PDA occurs quite frequently but is usually diagnosed too late, at its advanced stage. Screening for PDA is not very well defined except in subgroups of high-risk individuals with genetic disorders or with chronic pancreatitis. We present convincing, probable, and suggestive risk factors associated with pancreatic cancer, many of which are modifiable and should be introduced and implemented in our society.

  1. Pancreatic Surgery in the Laparoscopic Era

    Directory of Open Access Journals (Sweden)

    Ammori BJ

    2003-11-01

    subtotal pancreatectomy with or without preservation of the splenic vessels and spleen for neuroendocrine and cystic tumours, and in some patients with chronic pancreatitis is feasible and safe. In experienced hands, this minimally invasive approach reduces postoperative hospital stay and expedites recovery. However, the incidence of pancreatic fistula following distal resection is not any less than that of open surgery. Although the previous limited experience with laparoscopic pancreaticoduodenectomy was discouraging, the recent experience with the hand-assisted approach is quite favourable and is likely to expand.

  2. Prevention of pancreatic cancer

    OpenAIRE

    Stefan Kuroczycki-Saniutycz; Agnieszka Grzeszczuk; Zbigniew Wojciech Zwierz; Paweł Kołodziejczyk; Jakub Szczesiul; Beata Zalewska-Szajda; Krystyna Ościłowicz; Napoleon Waszkiewicz; Krzysztof Zwierz; Sławomir Dariusz Szajda

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDA) accounts for 95% of all pancreatic cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the lowest five-year survival rate as compared to others cancers. PDA in Poland is the fifth leading cause of death after lung, stomach, colon and breast cancer. In our paper we have analysed the newest epidemiological research, some of it controversial, to establish the best practical solution for pancreatic cancer prevention in the healthy...

  3. Effect of pioglitazone on in-stent restenosis after coronary drug-eluting stent implantation: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Ming-duo Zhang

    Full Text Available In-stent restenosis (ISR remains a common life-threatening complication and some studies have shown that pioglitazone can reduce the incidence of ISR in patients with drug-eluting stents (DES implantation. We conducted a meta-analysis to assess the effect of pioglitazone in preventing ISR after DES implantation.Randomized controlled trials (RCTs investigating the effects of pioglitazone for ISR after DES implantation were identified by systematic searches of multiple online databases and manual searches of related reference lists of identified trials through May 2014. The primary endpoint was the rate of ISR. Secondary endpoints included minimum lumen diameter, percentage stenosis of stented vessels, late loss, in-stent neointimal volume, target vessel revascularization (TVR, target lesion revascularization, myocardial infarction, stent thrombosis and death.Five studies, comprising 255 pioglitazone-treated patients and 245 controls, were identified in the current meta-analysis. Pioglitazone did not significantly reduce the rate of ISR (P = 0.20 with low heterogeneity (I2 = 13.3%, P = 0.32. For the secondary outcomes, pioglitazone did not substantially affect the pooled estimates of these endpoints except late loss (P = 0.01 and TVR (P = 0.04.The limited evidence indicates that pioglitazone does not demonstrate markedly beneficial effect in patients subjected to coronary DES implantation. However, the results should be interpreted with care given the small sample size. Further large-scale RCTs are needed.

  4. Risk of bladder cancer among patients with diabetes treated with a 15 mg pioglitazone dose in Korea: a multi-center retrospective cohort study.

    Science.gov (United States)

    Jin, Sang-Man; Song, Sun Ok; Jung, Chang Hee; Chang, Jin-Sun; Suh, Sunghwan; Kang, Seung Min; Jung, Inkyung; Park, Cheol-Young; Kim, Jae Hyeon; Cho, Jae Hyoung; Lee, Byung-Wan

    2014-02-01

    It has not yet been determined whether chronic exposure to relatively low doses of pioglitazone increases risk of bladder cancer. We aimed to assess the risk of bladder cancer associated with pioglitazone in Korean patients. This was a retrospective cohort study of diabetic patients who had ≥ 2 clinic visits between November 2005 and June 2011 at one of four tertiary referral hospitals in Korea. A prevalent case-control analysis nested within the cohort was conducted to further adjust confounders. A total of 101,953 control patients and 11,240 pioglitazone-treated patients were included, in which there were 237 and 30 cases of incidental bladder cancer (64.9 and 54.9 per 100,000 person-years; age, sex-adjusted HR 1.135, 95% confidence interval [CI] 0.769-1.677), respectively. In the prevalent case-control analysis nested within the cohort, use of pioglitazone for a duration of > 6 months, but not ever use of pioglitazone, was associated with an increased rate of bladder cancer as compared to never use of pioglitazone. In conclusion, we failed to exclude the possible association between use of pioglitazone for a duration of > 6 months and bladder cancer.

  5. Comparison of metabolic profile and adiponectin level with pioglitazone versus voglibose in patients with type-2 diabetes mellitus associated with metabolic syndrome.

    Science.gov (United States)

    Fujitaka, Keisuke; Otani, Hajime; Jo, Fusakazu; Jo, Hiromi; Nomura, Emiko; Iwasaki, Masayoshi; Nishikawa, Mitsushige; Iwasaka, Toshiji

    2011-01-01

    Type 2 diabetes mellitus (T2DM) associated with metabolic syndrome (MetS) represents a high risk of cardiovascular disease. We compared the effect of early intervention with pioglitazone versus voglibose on physical and metabolic profiles and serum adiponectin level in patients with T2DM associated with MetS. Sixty patients who were diagnosed for the first time as T2DM associated with MetS were analyzed for insulin sensitivity, lipid profile, serum adiponectin and systemic inflammation. Those patients were randomly assigned to oral pioglitazone group (n = 30) or voglibose group (n = 30) in addition to conventional diet and exercise training. Body mass index and waist circumference did not change in the pioglitazone group, whereas these physical parameters significantly decreased in the voglibose group during a 6-month follow-up period. However, glycosylated hemoglobin, fasting plasma glucose, and HOMA-IR more significantly decreased in the pioglitazone group. The level of serum adiponectin especially high-molecular weight adiponectin markedly increased in the pioglitazone group. Moreover, high sensitive CRP significantly decreased only in the pioglitazone group. These results suggest that voglibose is superior in improving obesity, while pioglitazone is superior in ameliorating insulin sensitivity and increasing serum adiponectin in patients with an early stage of T2DM associated with MetS.

  6. Cardioprotective effect of pioglitazone in diabetic and non-diabetic rats subjected to acute myocardial infarction involves suppression of AGE-RAGE axis and inhibition of apoptosis.

    Science.gov (United States)

    Khodeer, Dina M; Zaitone, Sawsan A; Farag, Noha E; Moustafa, Yasser M

    2016-05-01

    Insulin resistance increases risk of cardiovascular diseases. This work investigated the protective effect of pioglitazone on myocardial infarction (MI) in non-diabetic and diabetic rats, focusing on its role on advanced glycated endproducts (AGEs) and cardiac apoptotic machinery. Male rats were divided into 2 experiments: experiment I and II (non-diabetic and diabetic rats) were assigned as saline, MI (isoproterenol, 85 mg/kg, daily), and MI+pioglitazone (5, 10, and 20 mg/kg). Injection of isoproterenol in diabetic rats produced greater ECG disturbances compared to non-diabetic rats. Treatment with pioglitazone (5 mg/kg) reduced the infarct size and improved some ECG findings. Pioglitazone (10 mg/kg) enhanced ECG findings, improved the histopathological picture and downregulated apoptosis in cardiac tissues. Whereas the higher dose of pioglitazone (20 mg/kg) did not improve most of the measured parameters but rather worsened some of them, such as proapoptotic markers. Importantly, a positive correlation was found between serum AGEs and cardiac AGE receptors (RAGEs) versus caspase 3 expression in the two experiments. Therefore, the current effect of pioglitazone was, at least in part, mediated through downregulation of AGE-RAGE axis and inhibition of apoptosis. Consequently, these data suggest that pioglitazone, at optimized doses, may have utility in protection from acute MI.

  7. Pancreatic Pseudocyst: Therapeutic Dilemma

    Directory of Open Access Journals (Sweden)

    A. K. Khanna

    2012-01-01

    Full Text Available Pancreatic pseudocyst develops in both acute and chronic pancreatitis. It is an entity likely to either remain asymptomatic or develop devastating complications. Despite being diagnosed easily, treatment exercise is still at crossroads whether in the form of internal or external drainage or endoscopic, laparoscopic, or open intervention with a good radiological guidance. The therapeutic dilemma whether to treat a patient with a pancreatic pseudocyst, as well as when and with what technique, is a difficult one. This paper is intended to get information about diagnostic and therapeutic exercises most appropriate for acute and chronic pancreatic pseudocyst.

  8. Hypermutation In Pancreatic Cancer.

    Science.gov (United States)

    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. Pancreatic Cancer Genetics

    OpenAIRE

    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, ...

  10. Glucose counterregulation in diabetes secondary to chronic pancreatitis

    DEFF Research Database (Denmark)

    Larsen, S; Hilsted, J; Philipsen, E K

    1990-01-01

    Glucose counterregulation and hormonal responses after insulin-induced hypoglycemia were investigated in six patients with diabetes mellitus secondary to chronic pancreatitis, in seven with insulin-dependent (type I) diabetes mellitus, and in seven healthy subjects. Glucose counterregulation...... was identical in type I patients and in the patients with chronic pancreatitis, whereas both groups had impaired glucose recovery compared with the healthy subjects. The patients with chronic pancreatitis had no glucagon response to hypoglycemia, whereas epinephrine increased significantly. In an additional...... experiment, glucose recovery did not occur after hypoglycemia during concomitant beta-adrenoceptor blockade in these patients. In conclusion, glucose counterregulation is preserved but slightly impaired in patients with diabetes secondary to chronic pancreatitis, and the combination of total glucagon...

  11. Pancreatic Somatostatinoma Diagnosed Preoperatively: Report of a Case

    Directory of Open Access Journals (Sweden)

    Yasuhisa Mori

    2014-01-01

    Full Text Available Context Somatostatinoma is a rare neoplasm of the pancreas. Preoperative diagnosis is often difficult. Case report We report a 72-year-old woman with a pancreatic head tumor measuring 37 mm in diameter, and enlargement of the lymphnodes on the anterior surface of the pancreatic head and the posterior surface of the horizontal part of the duodenum.Laboratory data showed an elevated plasma somatostatin concentration. Examination of a biopsy specimen of thepancreatic head mass obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA showedhistopathological features of a neuroendocrine tumor. Immunohistochemical staining showed that the tumor cells werepositive for somatostatin, leading to a preoperative diagnosis of pancreatic somatostatinoma. The patient underwentpylorus-preserving pancreaticoduodenectomy. The plasma somatostatin concentration decreased progressively aftersurgery. Conclusions A rare case of pancreatic somatostatinoma with lymph node metastases was presented.Immunohistochemical analysis of a biopsy specimen obtained by EUS-FNA was useful for preoperative diagnosis.

  12. Effect of pioglitazone on arterial baroreflex sensitivity and sympathetic nerve activity in patients with acute myocardial infarction and type 2 diabetes mellitus.

    Science.gov (United States)

    Yokoe, Hiroshi; Yuasa, Fumio; Yuyama, Reisuke; Murakawa, Kousuke; Miyasaka, Yoko; Yoshida, Susumu; Tsujimoto, Satoshi; Sugiura, Tetsuro; Iwasaka, Toshiji

    2012-06-01

    Pioglitazone has been shown to reduce the occurrence of fatal and nonfatal myocardial infarction (MI) in type 2 diabetes mellitus (DM). However, the mechanisms of such favorable effects remain speculative. The aim of this study was to investigate the effect of pioglitazone on arterial baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA) in 30 DM patients with recent MI. Patients were randomly assigned to those taking pioglitazone (n = 15) and those not taking pioglitazone (n = 15) at 4 weeks after the onset of MI. BRS, MSNA, calculated homeostasis model assessment of insulin resistance index (HOMA-IR), and plasma adiponectin were measured at baseline and after 12 weeks. Pioglitazone increased plasma adiponectin (from 6.9 ± 3.3 μg/dL to 12.2 ± 7.1 μg/dL) and reduced HOMA-IR (from 4.0 ± 2.2 to 2.1 ± 0.9). In the pioglitazone group, MSNA decreased significantly (from 37 ± 7 bursts/min to 25 ± 8 bursts/min) and BRS increased significantly (from 6.7 ± 3.0 to 9.9 ± 3.2 ms/mm Hg) after 12 weeks. Furthermore, a significant relationship was found between the change in MSNA and HOMA-IR (r = 0.6, P = 0.042). Thus, pioglitazone decreased the sympathetic nerve traffic through the improvement of insulin resistance in DM patients with recent MI, which indicate that the sympathoinhibitory effects of pioglitazone may, at least in part, have contributed to the beneficial effects of pioglitazone.

  13. Metabolic and other effects of pioglitazone as an add-on therapy to metformin in the treatment of polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Valsamakis, Georgios; Lois, Kostas; Kumar, Sudhesh; Mastorakos, George

    2013-01-01

    Insulin resistance is a key pathogenic defect of the clustered metabolic disturbances seen in polycystic ovary syndrome (PCOS). Metformin is an insulin sensitizer acting in the liver and the peripheral tissues that ameliorates the metabolic and reproductive defects in PCOS. In addition, pioglitazone is an insulin sensitizer used in diabetes mellitus type 2 (T2DM), improving insulin resistance (IR) in adipose tissue and muscles. In T2DM, these drugs are also used as a combined treatment due to their "add-on effect" on insulin resistance. Although the beneficial role of troglitazone (a member of the thiazolidinediones (TZDs) family) in PCOS has been shown in the past, currently only pioglitazone is available in the market. A few small randomized controlled trials have directly compared the effectiveness of pioglitazone in women with PCOS, while there are a limited number of small studies that support the beneficial metabolic add-on effect of pioglitazone on metformin-treated PCOS women as compared to metformin or pioglitazone monotherapy. These findings suggest a potentially promising role for combined pioglitazone/metformin treatment in the management of PCOS in metformin-resistant patients. In view of recent concerns regarding pioglitazone usage and its associated health risk, we aim to compare the pros and cons of each drug regarding their metabolic and other hormonal effects in women with PCOS and to explore the possible beneficial effect of combined therapy in certain cases, taking into consideration the teratogenic effect of pioglitazone. Finally, we discuss the need for a randomized controlled trial that will evaluate the metabolic and other hormonal effects of combined metformin/pioglitazone treatment in PCOS with selective treatment targets.

  14. Effect of pioglitazone on outcome following curative treatment for hepatocellular carcinoma in patients with hepatitis C virus infection: A prospective study.

    Science.gov (United States)

    Sumie, Shuji; Kawaguchi, Takumi; Kawaguchi, Atsushi; Kuromatsu, Ryoko; Nakano, Masahito; Satani, Manabu; Yamada, Shingo; Okamura, Shusuke; Yonezawa, Yuko; Kakuma, Tatsuyuki; Torimura, Takuji; Sata, Michio

    2015-01-01

    Pioglitazone is an insulin sensitizer used for the treatment of diabetes mellitus (DM). DM with insulin resistance is a risk factor for hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection. We aimed to investigate the effects of pioglitazone on HCC recurrence following treatment in HCV-infected patients. Between 2009 and 2011, 85 HCV-infected HCC patients who underwent curative treatment were enrolled in this prospective study. Among 45 patients with type 2 DM, 27 were administered pioglitazone (pioglitazone group) following treatment. The remaining 58 patients were assigned to the control group. The primary outcome was recurrence-free survival. Changes in insulin resistance and serum adiponectin levels resulting from pioglitazone treatment were also assessed. In the whole analysis (n=85), no significant difference in recurrence-free survival was observed between the pioglitazone and control groups. However, in a spline model analysis of DM patients, a decreased risk of HCC recurrence was associated with increased body weight in patients with a body mass index (BMI) ≥23; this association became significant at BMI ≥24 (hazard ratio=0.17; 95% confidence interval: 0.03-0.95). In addition, significantly decreased homeostasis model assessment for insulin resistance values (P=0.002) and significantly increased serum high-molecular-weight adiponectin levels (Ppioglitazone treatment. Although pioglitazone did not suppress HCC recurrence in the whole analysis, it inhibited HCC recurrence in overweight HCV-infected diabetic patients. Moreover, pioglitazone improved insulin resistance and adipocytokine levels. Thus, pioglitazone may suppress HCC recurrence, which is associated with glucose and fat metabolism disorders.

  15. Hereditary pancreatitis: current perspectives

    Directory of Open Access Journals (Sweden)

    Raphael KL

    2016-07-01

    Full Text Available Kara L Raphael, Field F Willingham Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA Abstract: 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. Keywords: pancreatic cancer, chronic pancreatitis, idiopathic pancreatitis, pancreatitis, familial pancreatitis, genetic mutations

  16. Anti-diabetes drug pioglitazone ameliorates synaptic defects in AD transgenic mice by inhibiting cyclin-dependent kinase5 activity.

    Directory of Open Access Journals (Sweden)

    Jinan Chen

    Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a serine/threonine kinase that is activated by the neuron specific activators p35/p39 and plays many important roles in neuronal development. However, aberrant activation of Cdk5 is believed to be associated with the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease (AD and Parkinson's disease (PD. Here in the present study, enhanced Cdk5 activity was observed in mouse models of AD; whereas soluble amyloid-β oligomers (Aβ, which contribute to synaptic failures during AD pathogenesis, induced Cdk5 hyperactivation in cultured hippocampal neurons. Inhibition of Cdk5 activity by pharmacological or genetic approaches reversed dendritic spine loss caused by soluble amyloid-β oligomers (Aβ treatment. Interestingly, we found that the anti-diabetes drug pioglitazone could inhibit Cdk5 activity by decreasing p35 protein level. More importantly, pioglitazone treatment corrected long-term potentiation (LTP deficit caused by Aβ exposure in cultured slices and pioglitazone administration rescued impaired LTP and spatial memory in AD mouse models. Taken together, our study describes an unanticipated role of pioglitazone in alleviating AD and reveals a potential therapeutic drug for AD curing.

  17. The Effectiveness of Liraglutide in Nonalcoholic Fatty Liver Disease Patients with Type 2 Diabetes Mellitus Compared to Sitagliptin and Pioglitazone

    Directory of Open Access Journals (Sweden)

    Takamasa Ohki

    2012-01-01

    Full Text Available Background. Liraglutide leading to improve not only glycaemic control but also liver inflammation in non-alcoholic fatty liver disease (NAFLD patients. Aims. The aim of this study is to elucidate the effectiveness of liraglutide in NAFLD patients with type 2 diabetes mellitus (T2DM compared to sitagliptin and pioglitazone. Methods. We retrospectively enrolled 82 Japanese NAFLD patients with T2DM and divided into three groups (liraglutide: N = 26, sitagliptin; N = 36, pioglitazone; N = 20. We compared the baseline characteristics, changes of laboratory data and body weight. Results. At the end of follow-up, ALT, fast blood glucose, and HbA1c level significantly improved among the three groups. AST to platelet ratio significantly decreased in liraglutide group and pioglitazone group. The body weight significantly decreased in liraglutide group (81.8 kg to 78.0 kg, <0.01. On the other hands, the body weight significantly increased in pioglitazone group and did not change in sitagliptin group. Multivariate regression analysis indicated that administration of liraglutide as an independent factor of body weight reduction for more than 5% (OR 9.04; 95% CI 1.12–73.1, =0.04. Conclusions. Administration of liraglutide improved T2DM but also improvement of liver inflammation, alteration of liver fibrosis, and reduction of body weight.

  18. Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control - Results from the pioneer study

    NARCIS (Netherlands)

    Pfutzner, A; Marx, N; Lubben, G; Langenfeld, M; Walcher, D; Konrad, T; Forst, T

    2005-01-01

    OBJECTIVES This study was performed to assess whether the anti-inflammatory and antiatherogenic effects of pioglitazone suggested by animal experiments are reproducible in man and independent from improvements in metabolic control. BACKGROUND Type 2 diabetes is associated with increased cardiovascul

  19. Different effects of thiazolidinediones on cardiovascular risk in patients with type 2 diabetes mellitus: pioglitazone versus rosiglitazone.

    Science.gov (United States)

    Simó, R; Rodriguez, A; Caveda, E

    2010-07-02

    Cardiovascular disease remains the primary cause of mortality for patients with type 2 diabetes, which is characterized by insulin resistance. The thiazolidinediones (TZDs), also known as glitazones, are one of the pharmacological approaches to improve insulin sensitivity. At present, there are two available TZDs: pioglitazone and rosiglitazone. The common target of action for TZDs is the nuclear peroxisome proliferator-activated receptor-gamma (PPAR-gamma) that regulates the gene transcription involved in adipocyte differentiation and glucose and lipid metabolism. TZDs have shown similar effects on glycemic control, as well as on weight gain, fluid retention, increased risk of heart failure, and leg and forearm fractures. However, TZDs have differential effects on cardiovascular disease. This article will review the differential effects of pioglitazone and rosiglitazone on cardiovascular risk factors and outcomes, as well as the potential differences between them. Based upon available evidence, pioglitazone has a beneficial effect on cardiovascular disease. By contrast, it seems that rosiglitazone increases cardiovascular risk. The difference in lipid profile may be the main factor accounting for the superiority of pioglitazone in reducing cardiovascular risk.

  20. The effectiveness of liraglutide in nonalcoholic fatty liver disease patients with type 2 diabetes mellitus compared to sitagliptin and pioglitazone.

    Science.gov (United States)

    Ohki, Takamasa; Isogawa, Akihiro; Iwamoto, Masahiko; Ohsugi, Mitsuru; Yoshida, Haruhiko; Toda, Nobuo; Tagawa, Kazumi; Omata, Masao; Koike, Kazuhiko

    2012-01-01

    BACKGROUND. Liraglutide leading to improve not only glycaemic control but also liver inflammation in non-alcoholic fatty liver disease (NAFLD) patients. AIMS. The aim of this study is to elucidate the effectiveness of liraglutide in NAFLD patients with type 2 diabetes mellitus (T2DM) compared to sitagliptin and pioglitazone. METHODS. We retrospectively enrolled 82 Japanese NAFLD patients with T2DM and divided into three groups (liraglutide: N = 26, sitagliptin; N = 36, pioglitazone; N = 20). We compared the baseline characteristics, changes of laboratory data and body weight. RESULTS. At the end of follow-up, ALT, fast blood glucose, and HbA1c level significantly improved among the three groups. AST to platelet ratio significantly decreased in liraglutide group and pioglitazone group. The body weight significantly decreased in liraglutide group (81.8 kg to 78.0 kg, P pioglitazone group and did not change in sitagliptin group. Multivariate regression analysis indicated that administration of liraglutide as an independent factor of body weight reduction for more than 5% (OR 9.04; 95% CI 1.12-73.1, P = 0.04). CONCLUSIONS. Administration of liraglutide improved T2DM but also improvement of liver inflammation, alteration of liver fibrosis, and reduction of body weight.

  1. Revitalization of pioglitazone: the optimum agent to be combined with a sodium-glucose co-transporter-2 inhibitor.

    Science.gov (United States)

    DeFronzo, R A; Chilton, R; Norton, L; Clarke, G; Ryder, R E J; Abdul-Ghani, M

    2016-05-01

    The recently completed EMPA-REG study showed that empagliflozin significantly decreased the major adverse cardiac events (MACE) endpoint, which comprised cardiovascular death, non-fatal myocardial infarction (MI) and stroke, in patients with high-risk type 2 diabetes (T2DM), primarily through a reduction in cardiovascular death, without a significant decrease in either MI or stroke. In the PROactive study, pioglitazone decreased the MACE endpoint by a similar degree to that observed in the EMPA-REG study, through a marked reduction in both recurrent MI and stroke and a modest reduction in cardiovascular death. These observations suggest that pioglitazone might be an ideal agent to combine with empagliflozin to further reduce cardiovascular events in patients with high-risk diabetes as empagliflozin also promotes salt/water loss and would be expected to offset any fluid retention associated with pioglitazone therapy. In the present paper, we provide an overview of the potential benefits of combined pioglitazone/empagliflozin therapy to prevent cardiovascular events in patients with T2DM.

  2. A review of pioglitazone HCL and glimepiride in the treatment of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Mozhgan Dorkhan

    2007-11-01

    Full Text Available Mozhgan Dorkhan, Anders FridDepartment of Clinical Sciences, Division of Diabetes and Endocrinology, Lund University, Malmö University Hospital, SwedenAbstract: Type 2 diabetes (T2D is a progressive disorder with a consistent and steady increase in glycosylated hemoglobin (HbA1c over time associated with enhanced risk of micro- and macrovascular complications and a substantial reduction in life expectancy. There are three major pathophysiologic abnormalities associated with T2D: impaired insulin secretion, excessive hepatic glucose output, and insulin resistance in skeletal muscle, liver, and adipose tissue. These defects have been treated in clinical praxis by use of oral insulin secretagogues (sulfonylureas/glinides or insulin, biguanides, and thiazolidinediones (TZDs respectively. Pioglitazone HCL is an insulin sensitizer in the TZD family and glimepiride is an insulin secretagogue in the SU family. This article reviews mechanisms of action and clinical data behind the use of these two commonly used oral hypoglycemic agents with documented efficacy and good safety profile of once-daily administration, alone or in combination with insulin or metformin, in the management of T2D in terms of glycemic and non-glycemic effects, tolerability and side effects, and impact on vascular health.Keywords: pioglitazone, glimepiride, type 2 diabetes, thiazolidinediones, sulfonylureas

  3. DEVELOPMENT AND EVALUATION OF MICROBALLOONS OF PIOGLITAZONE HYDROCHLORIDE USING EUDRAGIT S-100

    Directory of Open Access Journals (Sweden)

    Nishant S. Gandhi et al.

    2012-01-01

    Full Text Available ABSTRACTKeywords:Pioglitazone hydrochloride,Eudragit S-100,Solvent diffusion evaporation,Floating microspheres,Polymer: Drug ratioCorrespondence to Author:Nishant GandhiOld Power House Road, Ramnagar, Gondia, Maharashtra, IndiaVarious approaches have been used to retain the dosage form in the stomach as a way of increasing the gastric residence time (GRT, including floatation systems; high-density systems; mucoadhesive systems; magnetic systems; unfoldable, extendible, or swellable systems; and superporous hydrogel systems. The aim of this study was to prepare and evaluate floating microspheres of Pioglitazone hydrochloride for the prolongation of gastric residence time. The microspheres were prepared by emulsion solvent diffusion-evaporation method using Eudragit S-100. A full factorial design was applied to optimize the formulation. Preliminary studies revealed that the concentration of polymer and stirring speed significantly affected the characteristics of floating microspheres. The optimum batch of microspheres exhibited some rough surfaces with good flow and packing properties, prolonged sustained drug release, remained buoyant for more than 10 hrs, high entrapment efficiency upto 89%w/w. Scanning electron microscopy confirmed the hollow structure with particle size in the order of 270 µm. The studies revealed that decrease in particle size of the microspheres increase the drug release from the floating microspheres. The results of 32 full factorial design revealed that the Polymer: Drug (P: D ratio (X1 and stirring speed (X2 significantly affected drug entrapment efficiency, percentage release after 8 h and particle size of microspheres.

  4. Development and optimization of novel controlled-release pioglitazone provesicular powders using 3² factorial design.

    Science.gov (United States)

    Shukr, Marwa H; Eltablawy, Nadia A

    2015-02-01

    This work aimed at studying a novel controlled drug delivery proniosomal formulation of pioglitazone for treatment of diabetes type-2. The effects of independent variables like type of surfactant and ratio of surfactants/cholesterol were studied using 3(2) factorial design. The provesicular powders were characterized regarding their encapsulation efficiency, vesicle size, morphology, and in vitro drug release. The revealed optimal provesicular powder was exposed to stability testing and in vivo performance evaluation. Results showed that F6 was selected as the optimal formulation, and its in vivo hypoglycemic effect on normal healthy and STZ-induced diabetic albino rats was investigated. F6 proniosomal formulation exhibited a significantly higher % decrease (56.18 % for STZ-induced diabetic albino rats) of blood glucose level (BGL) than Actos® (32. % for STZ-induced diabetic albino rats). Higher % decrease of BGL with longer t max and lower AUC0-24 confirms the development of a successful proniosomal pioglitazone formulation.

  5. Liquid Chromatographic Determination of Pioglitazone in Pharmaceuticals, Serum and Urine Samples

    Directory of Open Access Journals (Sweden)

    Shahnaz Perveen

    2011-12-01

    Full Text Available A rapid and reliable analytical method based on high-performance liquid chromatography (HPLC with UV detection (221nm has been developed for the determination of the anti-hyperglycemic agent Pioglitazone in pharmaceutical formulations and biological fluids (serum and urine after clean-up with solid-phase extraction. Chromatographic separation was achieved with a Chromolith® Performance RP-18e (100×4.6mm column using mobile phase composition of acetonitrile: mixed phosphate buffer (pH 2.5; 10mM (30:70, v/v with a flow rate of 2.0mL/min. The total run time was 2 min. under optimized conditions. The calibration curve was found to be linear in the range of 1-10 µg mL-1 with regression coefficient of 0.9996, and the lower limit of detection 72 ng/20µL injection. The method has been validated for the system suitability, linearity, precision and accuracy, limits of detection, specificity, stability and robustness. The %recovery of Pioglitazone in pharmaceutical formulations was found to be 104.7%. The assay has been applied successfully to the pharmaceutical Tablet samples and biological fluids (serum and urine of healthy volunteers.

  6. Regulation of Diet-Induced Adipose Tissue and Systemic Inflammation by Salicylates and Pioglitazone

    Science.gov (United States)

    Kamei, Nozomu; Shimada, Takeshi; Liu, Libin; Moore, Kristin; Woo, Ju Rang; Shoelson, Steven E.; Lee, Jongsoon

    2013-01-01

    It is increasingly accepted that chronic inflammation participates in obesity-induced insulin resistance and type 2 diabetes (T2D). Salicylates and thiazolidinediones (TZDs) both have anti-inflammatory and anti-hyperglycemic properties. The present study compared the effects of these drugs on obesity-induced inflammation in adipose tissue (AT) and AT macrophages (ATMs), as well as the metabolic and immunological phenotypes of the animal models. Both drugs improved high fat diet (HFD)-induced insulin resistance. However, salicylates did not affect AT and ATM inflammation, whereas Pioglitazone improved these parameters. Interestingly, HFD and the drug treatments all modulated systemic inflammation as assessed by changes in circulating immune cell numbers and activation states. HFD increased the numbers of circulating white blood cells, neutrophils, and a pro-inflammatory monocyte subpopulation (Ly6Chi), whereas salicylates and Pioglitazone normalized these cell numbers. The drug treatments also decreased circulating lymphocyte numbers. These data suggest that obesity induces systemic inflammation by regulating circulating immune cell phenotypes and that anti-diabetic interventions suppress systemic inflammation by normalizing circulating immune phenotypes. PMID:24376593

  7. Pioglitazone--do we really need it to manage type 2 diabetes?

    Science.gov (United States)

    Sinha, Binayak; Ghosal, Samit

    2013-01-01

    Over the last few years a number of important drugs like rofecoxib, rosiglitazone, gatifloxacin (in diabetics) have lost their position in disease management. The newest controversy revolves around Pioglitazone, a thiozolidindione, which improves insulin sensitivity and is reputed to have cardioprotective actions, but is riddled with several controversies related to weight gain, distal fractures of long bones, recent reports of bladder cancer and others. There are now new groups of drugs, which have been introduced with stringent FDA approval. These include DPP-4 inhibitors, GLP-1 analogues and bromocriptine (old wine in a new bottle). Early in 2013 we are also looking at the launch of another new agent - SGLT-2 inhibitors. These newer agents are associated with not only a significant glucose lowering effect but also positive extra-glycaemic benefits principally in the areas of hypoglycaemia and weight gain. This raises a very important question - do we really need such a controversial agent when such a plethora of agents are available to us with possibly better metabolic profile than pioglitazone? This review addresses this highly contentious area dissecting the pros and cons as we see it.

  8. Alogliptin in combination with metformin and pioglitazone for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Holland, Daniel Q; Neumiller, Joshua J

    2014-01-01

    Alogliptin is a selective dipeptidyl peptidase-4 inhibitor recently marketed for once-daily administration in the treatment of type 2 diabetes mellitus (T2DM). Fixed-dose combinations of alogliptin with both metformin and pioglitazone are also commercially available, providing a measure of convenience in addition to an effective mode of delivering combination therapy to improve glycemic control. Alogliptin has been studied clinically as initial therapy in treatment-naïve patients with T2DM and as initial therapy or add-on in combination with other antidiabetic agents. Clinical trial data with alogliptin demonstrate clinical efficacy in terms of glycosylated hemoglobin A1c and fasting plasma glucose reductions when used both as monotherapy and as a component of two- or three-drug combination regimens for the treatment of T2DM. Extensive Phase II and Phase III clinical trial data support the use of alogliptin in combination with metformin and pioglitazone. Glycemic reduction with both combinations is similar to the sum of the respective monotherapies, with adverse event rates similar - or more moderate - than those observed with up-titration of monotherapy or the addition of other antihyperglycemic agents.

  9. A Validated Adsorptive Stripping Voltammetric Determination of Antidiabetic Agent Pioglitazone HCl in Tablets and Biological Fluids

    Science.gov (United States)

    Al-Arfaj, Nawal Ahmad; Al-Abdulkareem, Eman Abdullah; Aly, Fatma Ahmad

    2008-01-01

    Square-wave adsorptive cathodic stripping voltammetry was used to determine pioglitazone HCl in Britton Robinson buffer of pH5. The adsorptive cathodic peak was observed at -1.5 V vs. Ag/AgCl. The peak response was characterized with respect to pH, supporting electrolyte, frequency, scan increment, pulse-amplitude, accumulation potential and pre-concentration time. Under optimal conditions, the peak current is proportional to the concentration of pioglitazone HCl, and a linear calibration graphs were obtained within the concentration levels of 10-8 and 10-4 M following different accumulation time periods (0-300 s). The obtained results were analyzed and the statistical parameters were calculated. The detection limit is 8.08 × 10-9 M (3.17 ng ml-1) using 300 s pre-concentration time, whereas the quantitative limit is 2.45 × 10-8 M (9.63 ng ml-1). The proposed method was applied to assay the drug in pharmaceutical formulations and biological fluids. The pharmacokinetic parameters of drug in human plasma were estimated as: Cmax=785.8 ng ml-1, tmax=1.5 h, Ke=0.125 h-1 and t1/2=8 h which are favorably compared with those reported in literature. PMID:23675103

  10. Endoscopic pancreatic duct stent placement for inflammatory pancreatic diseases

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The role of endoscopic therapy in the management of pancreatic diseases is continuously evolving; at present most pathological conditions of the pancreas are successfully treated by endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasound (EUS),or both. Endoscopic placement of stents has played and still plays a major role in the treatment of chronic pancreatitis, pseudocysts, pancreas divisum, main pancreatic duct injuries, pancreatic fistulae, complications of acute pancreatitis, recurrent idiopathic pancreatitis,and in the prevention of post-ERCP pancreatitis. These stents are currently routinely placed to reduce intraductal hypertension, bypass obstructing stones, restore lumen patency in cases with dominant, symptomatic strictures,seal main pancreatic duct disruption, drain pseudocysts or fluid collections, treat symptomatic major or minor papilla sphincter stenosis, and prevent procedure-induced acute pancreatitis. The present review aims at updating and discussing techniques, indications, and results of endoscopic pancreatic duct stent placement in acute and chronic inflammatory diseases of the pancreas.

  11. Treatment of necrotizing pancreatitis

    NARCIS (Netherlands)

    Brunschot, S. van; Bakker, O.J.; Besselink, M.G.; Bollen, T.L.; Fockens, P.; Gooszen, H.G.; Santvoort, H.C. van; Dutch Pancreatitis Study, G.

    2012-01-01

    Acute pancreatitis is a common and potentially lethal disease. It is associated with significant morbidity and consumes enormous health care resources. Over the last 2 decades, the treatment of acute pancreatitis has undergone fundamental changes based on new conceptual insights and evidence from cl

  12. Acute Recurrent Pancreatitis

    Directory of Open Access Journals (Sweden)

    Glen A Lehman

    2003-01-01

    Full Text Available History, physical examination, simple laboratory and radiological tests, and endoscopic retrograde cholangiopancreatography (ERCP are able to establish the cause of recurrent acute pancreatitis in 70% to 90% of patients. Dysfunction of the biliary and/or pancreatic sphincter, as identified by sphincter of Oddi manometry, accounts for the majority of the remaining cases. The diagnosis may be missed if the pancreatic sphincter is not evaluated. Pancreas divisum is a prevalent congenital abnormality that is usually innocuous but can lead to recurrent attacks of acute pancreatitis or abdominal pain. In select cases, endoscopic sphincterotomy of the minor papilla can provide relief of symptoms and prevent further attacks. A small proportion of patients with idiopathic pancreatitis have tiny stones in the common bile duct (microlithiasis. Crystals can be visualized during microscopic analysis of bile that is aspirated at the time of ERCP. Neoplasia is a rare cause of pancreatitis, and the diagnosis can usually be established by computerized tomography or ERCP. A wide variety of medications can also cause recurrent pancreatitis. ERCP, sphincter of Oddi manometry, and microscopy of aspirated bile should be undertaken in patients with recurrent pancreatitis in whom the diagnosis is not obvious.

  13. Orlistat-induced acute pancreatitis

    OpenAIRE

    2012-01-01

    Drug-induced pancreatitis is a rare but important cause of pancreatic injury. Orlistat is a pancreatic lipase inhibitor licensed for the treatment of obesity. We present a case of orlistat- induced mild acute pancreatitis that developed 8 days after starting treatment.

  14. Review of idiopathic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    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.

  15. Pancreatic and pulmonary mast cells activation during experimental acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Inmaculada; Lopez-Font; Sabrina; Gea-Sorlí; Enrique; de-Madaria; Luis; M; Gutiérrez; Miguel; Pérez-Mateo; Daniel; Closa

    2010-01-01

    AIM:To study the activation of pancreatic and pulmonary mast cells and the effect of mast cell inhibition on the activation of peritoneal and alveolar macrophages during acute pancreatitis.METHODS:Pancreatitis was induced by intraductal infusion of 5% sodium taurodeoxycholate in rats.The mast cell inhibitor cromolyn was administered intraperitoneally(i.p.) 30 min before pancreatitis induction.The pancreatic and pulmonary tissue damage was evaluated histologically and mast cells and their state of activation...

  16. Pioglitazone can ameliorate insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats

    Institute of Scientific and Technical Information of China (English)

    Shi-ying DING; Zhu-fang SHEN; Yue-teng CHEN; Su-juan SUN; Quan Liu; Ming-zhi XIE

    2005-01-01

    Aim: To investigate the effect of the peroxisome proliferator-activator receptor (PPAR)-γ agonist, pioglitazone, on insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats. Methods: Normal female Wistar rats were injected intraperitoneally with low-dose streptozotocin (STZ, 30 mg/kg) and fed with a high sucrose-fat diet for 8 weeks. Pioglitazone (20 mg/kg) was administered orally to the obese and insulin-resistant rats for 28 d. Intraperitoneal glucose tolerance tests, insulin tolerance tests and gluconeogenesis tests were carried out over the last 14 d. At the end of d 28 of the treatment, serums were collected for biochemical analysis. Glucose transporter 4 (GLUT4) and insulin receptor substrate-1 (IRS-1) protein expression in the liver and skeletal muscle were detected using Western blotting. Results: Significant insulin resistance and obesity were observed in low-dose STZ and high sucrose-fat diet induced obese rats. Pioglitazone (20 mg/kg) treatment significantly decreased serum insulin,triglyceride and free fatty acid levels, and elevated high density lipoprotein-cholesterol (HDL-C) levels. Pioglitazone also lowered the lipid contents in the liver and muscles of rats undergoing treatment. Gluconeogenesis was inhibited and insulin sensitivity was improved markedly. The IRS-1 protein contents in the liver and skeletal muscles and the GLUT4 contents in skeletal muscle were elevated significantly. Conclusion: The data suggest that treatment with pioglitazone improves insulin sensitivity in low-dose STZ and high sucrose-fat diet induced obese rats. The insulin sensitizing effect may be associated with ameliorating lipid metabolism, reducing hyperinsulinemia, inhibiting gluconeogenesis, and increasing IRS-1 and GLUT4 protein expression in insulin-sensitive tissues.

  17. Effects of pioglitazone mediated activation of PPAR-γ on CIDEC and obesity related changes in mice.

    Directory of Open Access Journals (Sweden)

    Bilal Haider Shamsi

    Full Text Available OBJECTIVE: Obesity is a metabolic disorder that can lead to high blood pressure, increased blood cholesterol and triglycerides, insulin resistance, and diabetes mellitus. The aim was to study the effects of pioglitazone mediated sensitization of peroxisome proliferator-activated receptor gamma (PPAR-γ on the relationship of Cell death-inducing DFFA-like effector C (CIDEC with obesity related changes in mice. METHODS: Sixty C57B/L6 mice weighing 10-12g at 3 weeks of age were randomly divided into 3 groups. Mice in Group 1 were fed on normal diet (ND while Group 2 mice were given high fat diet (HFD, and Group 3 mice were given high fat diet and treated with Pioglitazone (HFD+P. Body weight, length and level of blood sugar were measured weekly. Quantitative real-time PCR, fluorescence microscopy, and ELISA were performed to analyze the expression of CIDEC and PPAR-γ in visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT. RESULTS: Body weight and length of mice increased gradually with time in all groups. Blood sugar in HFD mice started to increase significantly from the mid of late phase of obesity while pioglitazone attenuated blood sugar level in HFD+P mice. The mRNA expressions and protein levels of PPAR-γ and CIDEC genes started to increase in HFD mice as compared to ND mice and decreased gradually during the late phase of obesity in VAT. Pioglitazone enhanced the expression of PPAR-γ and CIDEC genes in HFD+P mice even during the late phase of obesity. CONCLUSION: It is insinuated that VAT is associated with late phase obesity CIDEC decrease and insulin resistance, while pioglitazone enhances CIDEC through activation of PPAR-γ, increases its expression, and decreases lipolysis, hence preventing an increase of blood sugar in mice exposed to HFD.

  18. Pioglitazone, a PPARγ agonist, provides comparable protection to angiotensin converting enzyme inhibitor ramipril against adriamycin nephropathy in rat.

    Science.gov (United States)

    Ochodnicky, Peter; Mesarosova, Lucia; Cernecka, Hana; Klimas, Jan; Krenek, Peter; Goris, Maaike; van Dokkum, Richard P E; Henning, Robert H; Kyselovic, Jan

    2014-05-05

    Peroxisome proliferator-activated receptor γ (PPARγ) agonists have been shown to ameliorate diabetic nephropathy, but much less are known about their effects in non-diabetic nephropathies. In the present study, metabolic parameters, blood pressure, aortic endothelial function along with molecular and structural markers of glomerular and tubulointerstitial renal damage, were studied in a rat model of normotensive nephropathy induced by adriamycin and treated with PPARγ agonist pioglitazone (12mg/kg, po), angiotensin converting enzyme (ACE) inhibitor ramipril (1mg/kg, po) or their combination. Pioglitazone had no effect on systolic blood pressure, marginally reduced glycemia and improved aortic endothelium-dependent relaxation. In the kidney, pioglitazone prevented the development of proteinuria and focal glomerulosclerosis to the similar extent as blood-pressure lowering ramipril. Renoprotection provided by either treatment was associated with a reduction in the cortical expression of profibrotic plasminogen activator inhibitor-1 and microvascular damage-inducing endothelin-1, and a limitation of interstitial macrophage influx. Treatment with PPARγ agonist, as well as ACE inhibitor comparably affected renal expression of the renin-angiotensin system (RAS) components, normalizing increased renal expression of ACE and enhancing the expression of Mas receptor. Interestingly, combined pioglitazone and ramipril treatment did not provide any additional renoprotection. These results demonstrate that in a nondiabetic renal disease, such as adriamycin-induced nephropathy, PPARγ agonist pioglitazone provides renoprotection to a similar extent as an ACE inhibitor by interfering with the expression of local RAS components and attenuating related profibrotic and inflammatory mechanisms. The combination of the both agents, however, does not lead to any additional renal benefit.

  19. The Peroxisome Proliferator Activated Receptor‐γ Pioglitazone Improves Vascular Function and Decreases Disease Activity in Patients With Rheumatoid Arthritis

    Science.gov (United States)

    Marder, Wendy; Khalatbari, Shokoufeh; Myles, James D.; Hench, Rita; Lustig, Susan; Yalavarthi, Srilakshmi; Parameswaran, Aishwarya; Brook, Robert D.; Kaplan, Mariana J.

    2013-01-01

    Background Rheumatoid arthritis (RA) is associated with heightened mortality due to atherosclerotic cardiovascular disease (CVD). Inflammatory pathways in RA negatively affect vascular physiology and promote metabolic disturbances that contribute to CVD. We hypothesized that the peroxisome proliferator activated receptor‐γ (PPAR‐γ) pioglitazone could promote potent vasculoprotective and anti‐inflammatory effects in RA. Methods and Results One hundred forty‐three non‐diabetic adult RA patients (76.2% female, age 55.2±12.1 [mean±SD]) on stable RA standard of care treatment were enrolled in a randomized, double‐blind placebo controlled crossover trial of 45 mg daily pioglitazone versus placebo, with a 3‐month duration/arm and a 2‐month washout period. Pulse wave velocity of the aorta (PWV), brachial artery flow mediated dilatation (FMD), nitroglycerin mediated dilatation (NMD), microvascular endothelial function (reactive hyperemia index [RHI]), and circulating biomarkers of inflammation, insulin resistance, and atherosclerosis risk all were quantified. RA disease activity was assessed with the 28‐Joint Count Disease Activity Score (DAS‐28) C‐reactive protein (CRP) and the Short Form (36) Health Survey quality of life questionnaire. When added to standard of care RA treatment, pioglitazone significantly decreased pulse wave velocity (ie, aortic stiffness) (P=0.01), while FMD and RHI remained unchanged when compared to treatment with placebo. Further, pioglitazone significantly reduced RA disease activity (P=0.02) and CRP levels (P=0.001), while improving lipid profiles. The drug was well tolerated. Conclusions Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues. The clinical implications of these findings remain to be established. Clinical Trial Registration URL: ClinicalTrials.gov Unique Identifier: NCT00554853. PMID:24252844

  20. Pioglitazone, a PPARγ agonist rescues depression associated with obesity using chronic unpredictable mild stress model in experimental mice.

    Science.gov (United States)

    Kurhe, Yeshwant; Mahesh, Radhakrishnan

    2016-06-01

    Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ) agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS) induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD) for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o.)/escitalopram (10 mg/kg p.o.)/vehicle (10 ml/kg p.o.) daily from day 15-28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST), tail suspension test (TST) and elevated plus maze (EPM) were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.

  1. Pioglitazone, a PPARγ agonist rescues depression associated with obesity using chronic unpredictable mild stress model in experimental mice

    Directory of Open Access Journals (Sweden)

    Yeshwant Kurhe

    2016-06-01

    Full Text Available Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o./escitalopram (10 mg/kg p.o./vehicle (10 ml/kg p.o. daily from day 15–28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST, tail suspension test (TST and elevated plus maze (EPM were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.

  2. Pancreatic Involvement in Melioidosis

    Directory of Open Access Journals (Sweden)

    Vui Heng Chong

    2010-07-01

    Full Text Available Context Melioidosis is endemic to tropical regions and, despite the common occurrence of intra-abdominal abscesses, pancreatic involvement in melioidosis has not previously been reported. Objective We report our experience with pancreatic melioidosis. Patients All 65 patients treated for melioidosis who had computed tomography (CT scans were identified from prospective databases and were retrospectively reviewed. Main outcome measures A detailed review of cases with pancreas involvement was carried out. Results There were four cases (three males and one female; median age 29.5 years, range: 25-48 years with pancreatic melioidosis, giving a prevalence of 6.2%. All had predisposing conditions (two had poorly controlled diabetes mellitus and two had thalassemia for melioidosis. Fever (100%, anorexia (100%, weight loss (100%, rigor (75% and abdominal pain (75% were the most common symptoms at presentation and the median duration of symptoms before presentation was six weeks (range: 2-8 weeks. All pancreatic abscesses were detected on CT scan. Multiple foci involvement was common (3 to 6 sites: blood (4 patients, liver (3 patients, psoas muscle (2 patients, spleen (2 patients, infected ascites (2 patients and lung (1 patient. Pancreatic involvement ranged from multi-focal micro-abscesses to focal large abscesses and involved all parts of the pancreas (body 100%, head 75% and tail 50%. Associated pancreatic findings included splenic vein thrombosis, peripancreatic inflammation and peripancreatic fat streaking. All the pancreatic abscesses were resolved with antibiotics without requiring pancreatic abscess drainage (including one patient who died from disseminated melioidosis. Conclusion Pancreatic involvement typically occurs as part of multi-organ involvement and commonly manifests as multifoci micro-abscesses. Associated pancreatic abnormalities were also common. All responded to treatment without requiring drainage

  3. Total Pancreatectomy and Islet Auto-Transplantation as Treatment for Ampullary Adenocarcinoma in the Setting of Pancreatic Ductal Disruption Secondary to Acute Necrotizing Pancreatitis. A Case Report

    Directory of Open Access Journals (Sweden)

    Uroghupatei P Iyegha

    2012-03-01

    Full Text Available Context Ampullary adenocarcinoma is the third most common periampullary malignancy. Obstruction of the main pancreatic duct is linked with an increased incidence of acute pancreatitis. Acute necrotizing pancreatitis leading to pancreatic duct disruption carries significant morbidity. When these conditions occur in combination, the treatment can be drastically limited as pancreaticoduodenectomy is not a viable option in the setting of friable ductal tissue, which precludes pancreatic ductal anastomosis and can lead to the complications of leak or stricture. Case report Our patient is a 72-year-old woman who developed pancreatic ductal disruption and splenic vein thrombosis as a result of acute necrotizing pancreatitis. Concurrently, she was found to have an ampullary adenoma with high-grade dysplasia. Her treatment options were limited, as she was neither a candidate for pancreaticoduodenectomy given the ductal disruption nor total pancreatectomy, which would render her a brittle diabetic. She was successfully treated with total pancreatectomy and islet auto-transplantation thereby resecting her ampullary lesion while both avoiding a pancreatic anastomosis and preserving pancreatic endocrine beta-cell function. Conclusion We report a case where total pancreatectomy and islet auto-transplantation can be considered as a viable option for treatment of ampullary lesions in a setting where standard surgical options are suboptimal.

  4. Chronic pancreatitis and pancreatic cancer; the clinical aspects and treatment of pancreatic exocrine insufficiency

    NARCIS (Netherlands)

    E.C.M. Sikkens (Edmée)

    2013-01-01

    textabstractIn exocrine pancreatic insufficiency, the pancreas is unable to deliver a sufficient quantity of pancreatic enzymes to the small intestine to digest food. It may occur in several life threatening diseases, including chronic pancreatitis and pancreatic cancer. Due to this lack or

  5. Chronic pancreatitis and pancreatic cancer; the clinical aspects and treatment of pancreatic exocrine insufficiency

    NARCIS (Netherlands)

    E.C.M. Sikkens (Edmée)

    2013-01-01

    textabstractIn exocrine pancreatic insufficiency, the pancreas is unable to deliver a sufficient quantity of pancreatic enzymes to the small intestine to digest food. It may occur in several life threatening diseases, including chronic pancreatitis and pancreatic cancer. Due to this lack or absence

  6. Studies on linearty and assay using RP-HPLC and UV-visible spectroscopy for the drugs oxcarbazepine and pioglitazone before and after expiry period

    National Research Council Canada - National Science Library

    Suganya, S; Bright, A; Devi, T.S. Renuga

    2012-01-01

    .... In the present investigation RP-HPLC and UV-Visible spectroscopic methods are employed for estimation of drugs oxcarbazepine and pioglitazone in tablet dosage form before expiry period and 10-12 months after its expiry...

  7. HPLC method development, validation and its application to investigate in vitro effect of pioglitazone on the availability of H1 receptor antagonists

    Directory of Open Access Journals (Sweden)

    Agha Zeeshan Mirza

    2017-02-01

    Full Text Available The method has been developed and validated for the simultaneous determination of pioglitazone and H1-receptor antagonists (fexofenadine, cetirizine and levocetirizine in formulations and human serum. Utilizing HPLC techniques, an assay was designed to determine the in vitro effects of pioglitazone on H1-receptor antagonists. Obtained results were verified using the UV spectrophotometric technique. First-derivative values versus concentrations were used to plot calibration curves of these drugs and were found to similar with the HPLC data. The availability of pioglitazone remained unchanged in absence or presence of fexofenadine, cetirizine and levocetirizine. This in vitro analysis confirms the harmless co-administration of pioglitazone and H1-receptor antagonists, and can serve as the foundation for designing further in vivo studies.

  8. [Etiological factors of acute pancreatitis].

    Science.gov (United States)

    Spicák, J

    2002-09-01

    Acute pancreatitis develops immediately after the causative impulse, while chronic pancreatitis develops after the long-term action of the noxious agent. A typical representative of acute pancreatitis is biliary pancreatitis, chronic pancreatitis develops in alcoholism and has a long latency. As alcoholic pancreatitis is manifested at first as a rule by a potent attack, it is classified in this stage as acute pancreatitis. The most frequent etiological factors in our civilization are thus cholelithiasis and alcoholism (both account for 20-50% in different studies). The assumed pathogenetic principles in acute biliary pancreatitis are the common canal of both efferent ducts above the obturated papilla, duodenopancreatic reflux and intrapancreatic hypertension. A detailed interpretation is however lacking. The pathogenesis of alcoholic pancreatitis is more complicated. Among others some part is played by changes in the calcium concentration and fusion of cellular membranes. Idiopathic pancreatitis occurs in up to 10%, part of the are due to undiagnosed alcoholism and cholelithiasis. Other etiologies are exceptional. Similarly as in cholelithiasis pancreatitis develops also during other pathological processes in the area of the papilla of Vater such as dysfunction of the sphincter of Oddi, ampulloma and juxtapapillary diverticulum, it is however usually mild. The incidence of postoperative pancreatitis is declining. Its lethality is 30% and the diagnosis is difficult. In the pathogenesis changes of the ion concentration are involved, hypoxia and mechanical disorders of the integrity of the gland. Pancreatitis develops in association with other infections--frequently in mumps, rarely in hepatitis, tuberculosis, typhoid and mycoses. Viral pancreatitis is usually mild. In parasitoses pancreatitis develops due to a block of the papilla Vateri. In hyperparathyroidism chronic pancreatitis is more likely to develop, recent data are lacking. As to dyslipoproteinaemias

  9. 保留十二指肠的胰头切除术与胰十二指肠切除术治疗胰头肿块型胰腺炎的Meta分析%A meta-analysis of surgery treatment of chronic pancreatitis with an inflammatory mass in the head of pancreas: duodenum-preserving pancreatic head resection versus pancreatoduodenectomy

    Institute of Scientific and Technical Information of China (English)

    蒋康怡; 吴柯; 廖玉平; 涂兵

    2014-01-01

    Objective To compare the safety and effectiveness of DPPHR with PPPD/PD for treating chronic pancreatitis with an inflammatory mass in the head of pancreas.Methods The relative data bases such as Medline,EMBase,Biosis,COCHRANE Library,Science Citation Index,SinoMed,Chinese Journal Full-text Database,Wangfang,CNKI were searched systematically,researchers selected randomized controlled trials(RCT) and prospective clinical controlled trials(CCT).The assessment of the bias risk of the included trials was according to the assessing tools suggested by Cochrane Handbook 5.1.The Review Manage 5.2 was used to perform the statistical analysis.Results In total,5 RCTs and 2 CCTs were included,381 patients involved.Comparing with PPPD/PD procedure,DPPHR has no significant difference in terms of the mortality of perioperative period (RD =0.01,P =0.51),the incidence of bleeding (RD =-0.01,P =0.72),pancreatic fistula (RD =-0.01,P =0.59) and delayed gastric emptying (RD =-0.15,P =0.10),the ration of complete pain relief after operation(RR =1.06,P =0.32) and the score of global quality of life(WMD =10.31,P =0.19).While DPPHR had significant superiorities in terms of the total morbidity of perioperative period (RR =0.60,P =0.008),the duration of the operations (WMD =-71.60,P =0.03),the postoperative hospitalization duration (WMD =-3.95,P < 0.01),weight gain (WMD =3.68,P < 0.01),occupational rehabilitation after the operations (RR =1.38,P =0.008).Conclusions In terms of reducing the morbidity of perioperative period,shortening the duration of the operations and the postoperative hospitalization duration,weight gain,occupational rehabilitation after the operations,the DPPHR is more favorable for improving patients' life qualities comparing with PPPD/PD.%目的 探讨保留或不保留幽门的胰十二指肠切除术(PPPD/PD)与保留十二指肠的胰头切除术(DPPHR)治疗胰头肿块型胰腺炎的安全性和有效性.方法 系统检索Medline数据库、EMBase

  10. Risk factors for postoperative pancreatic fistula: Analysis of 539 successive cases of pancreaticoduodenectomy.

    Science.gov (United States)

    Hu, Bing-Yang; Wan, Tao; Zhang, Wen-Zhi; Dong, Jia-Hong

    2016-09-14

    To analyze the risk factors for pancreatic fistula after pancreaticoduodenectomy. We conducted a retrospective analysis of 539 successive cases of pancreaticoduodenectomy performed at our hospital from March 2012 to October 2015. Pancreatic fistula was diagnosed in strict accordance with the definition of pancreatic fistula from the International Study Group on Pancreatic Fistula. The risk factors for pancreatic fistula were analyzed by univariate analysis and multivariate logistic regression analysis. A total of 269 (49.9%) cases of pancreatic fistula occurred after pancreaticoduodenectomy, including 71 (13.17%) cases of grade A pancreatic fistula, 178 (33.02%) cases of grade B, and 20 (3.71%) cases of grade C. Univariate analysis showed no significant correlation between postoperative pancreatic fistula (POPF) and the following factors: age, hypertension, alcohol consumption, smoking, history of upper abdominal surgery, preoperative jaundice management, preoperative bilirubin, preoperative albumin, pancreatic duct drainage, intraoperative blood loss, operative time, intraoperative blood transfusion, Braun anastomosis, and pancreaticoduodenectomy (with or without pylorus preservation). Conversely, a significant correlation was observed between POPF and the following factors: gender (male vs female: 54.23% vs 42.35%, P = 0.008), diabetes (non-diabetic vs diabetic: 51.61% vs 39.19%, P = 0.047), body mass index (BMI) (≤ 25 vs > 25: 46.94% vs 57.82%, P = 0.024), blood glucose level (≤ 6.0 mmol/L vs > 6.0 mmol/L: 54.75% vs 41.14%, P = 0.002), pancreaticojejunal anastomosis technique (pancreatic duct-jejunum double-layer mucosa-to-mucosa pancreaticojejunal anastomosis vs pancreatic-jejunum single-layer mucosa-to-mucosa anastomosis: 57.54% vs 35.46%, P = 0.000), diameter of the pancreatic duct (≤ 3 mm vs > 3 mm: 57.81% vs 38.36%, P = 0.000), and pancreatic texture (soft vs hard: 56.72% vs 29.93%, P = 0.000). Multivariate logistic regression analysis showed that

  11. Latest advances in chronic pancreatitis.

    Science.gov (United States)

    Enrique Domínguez-Muñoz, J

    2016-09-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the definition of the disease, the etiological diagnosis of idiopathic disease, the correlation between fibrosis degree and pancreatic secretion in the early stages of chronic pancreatitis, the treatment of the disease and of pain, the clinical relevance of pancreatic exocrine insufficiency, and the diagnosis of autoimmune pancreatitis. A new mechanistic definition of chronic pancreatitis has been proposed. Genetic testing is mainly of help in patients with relapsing idiopathic pancreatitis. A significant correlation has been shown between the degree of pancreatic fibrosis as evaluated by elastography and pancreatic secretion of bicarbonate. New data supports the efficacy of antioxidants and simvastatin for the therapy of chronic pancreatitis. The pancreatoscopy-guided intraductal lithotripsy is an effective alternative to extracorporeal shock wave lithotripsy in patients with chronic calcifying pancreatitis. The presence of pancreatic exocrine insufficiency in patients with chronic pancreatitis is associated with a significant risk of cardiovascular events. Fine needle biopsy and contrast enhanced harmonic endoscopic ultrasonography are of help for the diagnosis of autoimmune pancreatitis and its differential diagnosis with pancreatic cancer. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  12. Impaired insulin activation and dephosphorylation of glycogen synthase in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Nicoline Resen

    2008-01-01

    . No significant abnormalities in GSK-3alpha or -3beta were found in PCOS subjects. Pioglitazone treatment improved insulin-stimulated glucose metabolism and GS activity in PCOS (all P ... of GS including absent dephosphorylation at sites 2+2a contributes to insulin resistance in skeletal muscle in PCOS. The ability of pioglitazone to enhance insulin sensitivity, in part, involves improved insulin action on GS activity and dephosphorylation at NH2-terminal sites....

  13. Pancreatic groove cancer

    Science.gov (United States)

    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

  14. Updates on Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Ojas Vyas

    2014-05-01

    Full Text Available Pancreatic adenocarcinoma remains a therapeutic challenge. The American Cancer Society estimates that in 2014 about 46,420 people will be diagnosed with pancreatic cancer and about 39,590 people will die of pancreatic cancer in the United States [1]. The incidence of pancreatic carcinoma has markedly increased over the past several decades and it now ranks as the fourth leading cause of cancer-related death in the United States. Despite the high mortality rate associated with pancreatic cancer, its etiology is poorly understood. Although progress in the development of new cytotoxic and biological drugs for the treatment of pancreatic cancer continues, the outcome remains grim. Many organizations and associations have taken an effort to improve knowledge, understanding and outcome of patients with pancreatic cancer. Pancreas Club, since its founding in 1966, is aimed to promote the interchange of ideas between physicians and scientists focused on pancreas throughout the world in an informal “club” atmosphere. We attended the 48th Annual Meeting of Pancreas Club in Chicago and reviewed many interesting posters and oral presentations. Here we discuss a few selected abstracts.

  15. Epidemiology of pancreatic cancer.

    Science.gov (United States)

    Ilic, Milena; Ilic, Irena

    2016-11-28

    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 11(th) 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.

  16. Familial pancreatic cancer.

    Science.gov (United States)

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

    2001-01-01

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

  17. [Treatment of acute pancreatitis].

    Science.gov (United States)

    Naumovski-Mihalić, Slavica

    2009-01-01

    Acute pancreatitis is an autodigestive disease in which the pancreatic tissue is damaged by the digestive enzimes produces by the acinar cells and is associated with severe upper abdominal pain. The severity of acute pancreatitis ranges from edema to necrosis of the gland. The edematous form of the disease occurs in about 80-85% of patients and is self-limited, with recovery in few days. In the 15-20% of patients with the most severe form of pancreatitis, hospitalization is prolonged and commonly associated with infection and other complications including multiple organ failure. The main causes of acute pancreatitis in adults are gallstones, other gallbladder (biliary) diseases and alcohol abuse. Treatment of acute pancreatitis-depends on the severity oft he condition. Generaly, the patients need, hospitalisation with administration of intravenous fluid to help restore blood volume, pain control, supplemental oxygen as required and correction of electrolite and metabolic abnormalities. Antibiotic prophylaxis has not been shown as an effective preventive treatment. Early enteral feeding is based on a high level of evidence, resulting in a reduction of local and sistemic infection. Begin oral feeding once abdominal pain has resolved and the patients regains appetite. The diet should be low in fat and protein. Patients suffering from infected necrosis causing clinical sepsis, pancreatic abscess or surgical acute abdomen are candidates for early intervention. During recent years the management of acute pancreatitis has changed. This has been due particulary in response to the general availability of computed tomography, improved intensive care facilities, knowledge about the central role of pancreatic infection and refinements in surgical and other interventional techniques.

  18. Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary-gonadal axis.

    Science.gov (United States)

    Abd El-Twab, Sanaa M; Mohamed, Hanaa M; Mahmoud, Ayman M

    2016-06-01

    Chronic hyperglycemia is associated with impairment of testicular function. The current study aimed to investigate the protective effects and the possible mechanisms of taurine and pioglitazone against diabetes-induced testicular dysfunction in rats. Diabetes was induced by streptozotocin injection. Both normal and diabetic rats received taurine (100 mg/kg) or pioglitazone (10 mg/kg) orally and daily for 6 weeks. Diabetic rats showed a significant (P Taurine and pioglitazone alleviated hyperglycemia, decreased pro-inflammatory cytokines, and increased circulating levels of insulin, testosterone, LH, and FSH. Gene and protein expression of LH and FSH receptors and cytochrome P450 17α-hydroxylase (CYP17) was significantly (P taurine and pioglitazone. In addition, taurine and pioglitazone significantly decreased lipid peroxidation and DNA damage, and enhanced activity of the antioxidant enzymes in testes of diabetic rats. In conclusion, taurine and pioglitazone exerted protective effects against diabetes-induced testicular damage through attenuation of hyperglycemia, inflammation, oxidative stress and DNA damage, and up-regulation of the pituitary/gonadal axis.

  19. Replicate study design in bioequivalency assessment, pros and cons: bioavailabilities of the antidiabetic drugs pioglitazone and glimepiride present in a fixed-dose combination formulation.

    Science.gov (United States)

    Karim, Aziz; Zhao, Zhen; Slater, Margaret; Bradford, Dawn; Schuster, Jennifer; Laurent, Aziz

    2007-07-01

    An open-label, randomized, 2-sequence, 4-period crossover (7-day washout period between treatment), replicate design study was conducted in 37 healthy subjects to assess intersubject and intrasubject variabilities in the peak (Cmax) and total (AUC) exposures to 2 oral antidiabetic drugs, pioglitazone and glimepiride, after single doses of 30 mg pioglitazone and 4 mg glimepiride, given under fasted state, as commercial tablets coadministered or as a single fixed-dose combination tablet. Variabilities for AUC(infinity) for coadministered and fixed-dose combination treatments were similar: 16% to 19% (intra) and 23% to 25% (inter) for pioglitazone and 18% to 19% (intra) and 29% to 30% for glimepiride (inter, excluding 1 poor metabolizer). Fixed-dose combination/coadministered least squares mean ratios of >or=0.86 and the 90% confidence intervals of these ratios for pioglitazone and glimepiride of between 0.80 and 1.25 for Cmax, AUC(lqc), and AUC(infinity) met the bioequivalency standards. Gender analysis showed that women showed mean of 16% and 30% higher exposure than men for glimepiride (excluding 1 poor metabolizer) and pioglitazone, respectively. There was considerable overlapping in the AUC(infinity) values, making gender-dependent dosing unnecessary. Patients taking pioglitazone and glimepiride as cotherapy may replace their medication with a single fixed-dose combination tablet containing these 2 oral antidiabetic drugs.

  20. Comparison of the efficacy of cardamom (Elettaria cardamomum with pioglitazone on dexamethasone-induced hepatic steatosis, dyslipidemia, and hyperglycemia in albino rats

    Directory of Open Access Journals (Sweden)

    G M Nitasha Bhat

    2015-01-01

    Full Text Available To evaluate the efficacy of cardamom with pioglitazone on dexamethasone-induced hepatic steatosis, dyslipidemia, and hyperglycemia in albino rats. There were four groups of 6 rats each. First group received dexamethasone alone in a dose of 8 mg/kg intraperitoneally for 6 days to induce metabolic changes and considered as dexamethasone control. Second group received cardamom suspension 1 g/kg/10 mL of 2% gum acacia orally 6 days before dexamethasone and 6 days during dexamethasone administration. Third group received pioglitazone 45 mg/kg orally 6 days before dexamethasone and 6 days during dexamethasone administration. Fourth group did not receive any medication and was considered as normal control. Fasting blood sugar, lipid profile, blood sugar 2 h after glucose load, liver weight, liver volume were recorded, and histopathological analysis was done. The effects of cardamom were compared with that of pioglitazone. Dexamethasone caused hepatomegaly, dyslipidemia and hyperglycemia. Both pioglitazone and cardamom significantly reduced hepatomegaly, dyslipidemia, and hyperglycemia (P < 0.01. Reduction of blood sugar levels after glucose load was significant with pioglitazone in comparison to cardamom (P < 0.01. Cardamom has comparable efficacy to pioglitazone in preventing dexamethasone-induced hepatomegaly, dyslipidemia, and fasting hyperglycemia.

  1. Long-term effects of pioglitazone on first attack of ischemic cerebrovascular disease in older people with type 2 diabetes: A case-control study in Taiwan.

    Science.gov (United States)

    Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu

    2016-08-01

    Long-term studies demonstrating the effect of pioglitazone use on primary prevention of ischemic cerebrovascular disease in older people with type 2 diabetes mellitus are lacking. This study investigated the relationship between pioglitazone use and first attack of ischemic cerebrovascular disease in Taiwan.We conducted a case-control study using the database of the Taiwan National Health Insurance Program. There were 2359 type 2 diabetic subjects aged ≥65 years with newly diagnosed ischemic cerebrovascular disease from 2005 to 2011 as the case group and 4592 sex- and age-matched, randomly selected type 2 diabetic subjects aged ≥65 years without ischemic cerebrovascular disease as the control group. The odds ratio (OR) with 95% confidence interval (CI) of ischemic cerebrovascular disease associated with pioglitazone use was measured by the multivariable unconditional logistic regression model.After adjustment for confounding factors, the multivariable logistic regression analysis disclosed that the adjusted ORs of first attack of ischemic cerebrovascular disease associated with cumulative duration of using pioglitazone were 3.34 for pioglitazone use does not have a protective effect on primary prevention for ischemic cerebrovascular disease among older people with type 2 diabetes mellitus during the first 3 years of use. Whether using pioglitazone for >3 years would have primary prevention for ischemic cerebrovascular disease needs a long-term research to prove.

  2. Suppressive effect of pioglitazone, a PPAR gamma ligand, on azoxymethane-induced colon aberrant crypt foci in KK-Ay mice.

    Science.gov (United States)

    Ueno, Toshiya; Teraoka, Naoya; Takasu, Shinji; Nakano, Katsuya; Takahashi, Mami; Yamamoto, Masafumi; Fujii, Gen; Komiya, Masami; Yanaka, Akinori; Wakabayashi, Keiji; Mutoh, Michihiro

    2012-01-01

    Obesity is an established risk factor for colorectal cancer. Pioglitazone is a peroxisome proliferator- activated receptor γ(PPARγ) agonist that induces differentiation in adipocytes and induces growth arrest and/or apoptosis in vitro in several cancer cell lines. In the present study, we investigated the effect of pioglitazone on the development of azoxymethane-induced colon aberrant crypt foci (ACF) in KK-Ay obesity and diabetes model mice, and tried to clarify mechanisms by which the PPARγ ligand inhibits ACF development. Administration of 800 ppm pioglitazone reduced the number of colon ACF / mouse to 30% of those in untreated mice and improved hypertrophic changes of adipocytes in KK-Ay mice with significant reduction of serum triglyceride and insulin levels. Moreover, mRNA levels of adipocytokines, such as leptin, monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1, in the visceral fat were decreased. PCNA immunohistochemistry revealed that pioglitazone treatment suppressed cell proliferation in the colorectal epithelium with elevation of p27 and p53 gene expression. These results suggest that pioglitazone prevented obesity-associated colon carcinogenesis through improvement of dysregulated adipocytokine levels and high serum levels of triglyceride and insulin, and increase of p27 and p53 mRNA levels in the colorectal mucosa. These data indicate that pioglitazone warrants attention as a potential chemopreventive agent against obesity-associated colorectal cancer.

  3. Modulating effects of omega-3 fatty acids and pioglitazone combination on insulin resistance through toll-like receptor 4 in type 2 diabetes mellitus.

    Science.gov (United States)

    Eraky, Salma M; Abdel-Rahman, Noha; Eissa, Laila A

    2017-06-17

    Toll-like receptor 4 (TLR-4) plays important roles in innate immunity. Changes in the reduction-oxidation balance of tissues can lead to a pro-inflammatory state and insulin resistance. An action thought to be mediated by TLRs. Omega-3 fatty acids and Peroxisome Proliferator Activated Receptor gamma (PPAR-γ) agonists as pioglitazone are used for decreasing inflammation. The aim of this study is to investigate the anti-diabetic effects of combining omega -3 fatty acid with pioglitazone on type 2 diabetes, and the modifying effects on TLR-4. Type 2 diabetes was induced in male Sprague-Dawley rats by combination of high fat diet and low dose streptozotocin (35mg/kg). Diabetic rats were treated with omega-3 fatty acids (10% W/W diet), pioglitazone (20mg/kg), and their combination for 4 weeks. Omega-3 fatty acids and the combination treatment significantly decreased TLR-4 activation. Omega-3 fatty acids, pioglitazone, and their combination significantly decreased TLR-4 mRNA expression, hepatic malondialdehyde, total cholesterol and triglycerides levels, compared to diabetic group. Pioglitazone and the combination significantly decreased blood glucose levels and improved insulin resistance. In conclusion, combining omega-3 fatty acids with pioglitazone showed potential effects in lowering blood glucose levels and improving lipid profile and insulin resistance. Such effects are mediated through modulation of TLR-4. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Effects of bed-time insulin versus pioglitazone on abdominal fat accumulation, inflammation and gene expression in adipose tissue in patients with type 2 diabetes.

    Science.gov (United States)

    Hartemann-Heurtier, Agnès; Halbron, Marine; Golmard, Jean-Louis; Jacqueminet, Sophie; Bastard, Jean-Philippe; Rouault, Christine; Ayed, Amine; Pieroni, Laurence; Clément, Karine; Grimaldi, André

    2009-10-01

    Intra-abdominal fat (IAF) and inflammatory markers are correlated with cardio-vascular risk. We compared the impact of bed-time insulin versus pioglitazone treatment on these parameters in type 2 diabetic (T2D) patients. Twenty-eight T2D patients poorly controlled with metformin and sulfonylurea were randomized to receive add-on therapy with pioglitazone or bed-time NPH insulin. IAF and subcutaneous fat (SCF) content, systemic low-grade inflammation level and expression of inflammation related genes in SCF, were measured before and after 24 weeks of treatment. Insulin and pioglitazone resulted in a significant decrease in HbA1c (-1.6% and -1.2%, respectively) and a significant increase in total body fat mass (1+/-2.3 and 3.3+/-2.7 kg, respectively). There was no change in IAF content after both treatments whereas significant increase in SCF content was only seen after pioglitazone treatment (pinsulin). hsCRP level decreased after pioglitazone and ferritin level decreased after insulin treatment. No change in mRNA expression of inflammation related genes was found after either treatment. This suggests that a 24-week treatment with pioglitazone or bed-time insulin has a similar impact on intra-abdominal fat mass and systemic low-grade inflammation.

  5. Pancreatitis in scrub typhus

    Directory of Open Access Journals (Sweden)

    Alok Bhatt

    2014-01-01

    Full Text Available Scrub typhus is a rickettsial infection prevalent in most parts of India. Acute pancreatitis with pseudocyst formation is a rare complication of this condition. This paper reports acute renal failure, pancreatitis and pseudocyst formation in a 48-year-old female with scrub typhus. Ultrasonography of the abdomen revealed a bulky pancreas with fluid seen along the body of the pancreas in the lesser sac. The infection was successfully treated with doxycycline and supportive treatment. Pancreatitis was managed conservatively. This case report highlights the importance of identifying and managing uncommon complications of a common tropical disease for optimum outcome.

  6. Danish Pancreatic Cancer Database

    DEFF Research Database (Denmark)

    Fristrup, Claus; Detlefsen, Sönke; Palnæs Hansen, Carsten

    2016-01-01

    AIM OF DATABASE: The Danish Pancreatic Cancer Database aims to prospectively register the epidemiology, diagnostic workup, diagnosis, treatment, and outcome of patients with pancreatic cancer in Denmark at an institutional and national level. STUDY POPULATION: Since May 1, 2011, all patients......, and survival. The results are published annually. CONCLUSION: The Danish Pancreatic Cancer Database has registered data on 2,217 patients with microscopically verified ductal adenocarcinoma of the pancreas. The data have been obtained nationwide over a period of 4 years and 2 months. The completeness...

  7. Delayed internal pancreatic fistula with pancreatic pleural effusion postsplenectomy

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The occurrence of pancreatic pleural effusion,secondary to an internal pancreatic fistula,is a rare clinical syndrome and diagnosis is often missed.The key to the diagnosis is a dramatically elevated pleural fluid amylase.This pancreatic pleural effusion is also called a pancreatic pleural fistula.It is characterized by profuse pleural fluid and has a tendency to recur.Here we report a case of delayed internal pancreatic fistula with pancreatic pleural effusion emerging after splenectomy.From the treatment ...

  8. Autoimmune pancreatitis characterized by predominant CD8+ T lymphocyte infiltration

    Institute of Scientific and Technical Information of China (English)

    She-Yu Li; Xiang-Yang Huang; Yong-Tao Chen; Yi Liu; Sha Zhao

    2011-01-01

    Autoimmune pancreatitis (AIP) is a rare form of pancreatitis characterized by prominent lymphocyte infiltration and pancreatic fibrosis resulting in organ dysfunction.The pathogenesis and pathology of AIP remain unknown. A 64-year-old Chinese man presented with symptoms and signs of bile duct obstruction diffuse enlargement of the head of pancreas, elevated IgG levels, and negative autoimmune antibody responses. A pylorus-preserving pancreatoduodenectomy was performed and a pancreatic tumor was suspected. However,periductal lymphoplasmacytic infiltration and fibrosis were found in the head of pancreas and nearby organs instead of tumor cells. Four months after surgery, the patient was readmitted because of reoccurrence of severe jaundice and sustained abdominal distension. Prednisone 30 mg/d was administered orally as an AIP was suspected. One and a half months later, the symptoms of the patient disappeared, and globulin, aminotransferase and bilirubin levels decreased significantly. Over a 9-mo follow-up period, the dose of prednisone was gradually decreased to 10 mg/d and the patient remained in good condition. We further demonstrated dominant CD3+/CD8+ populations, CD20+ cells and a few CD4+ cells in the pancreatic parenchyma, duodenum and gallbladder wall by immunohistochemical assay. This AIP case presented with significant CD8+ T lymphocyte infiltration in the pancreas and extra-pancreatic lesions, indicating that this cell population may be more important in mediating AIP pathogenesis than previously known and that AIP might be a poorly defined autoimmune disease with heterogeneous pathogenesis.

  9. Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients.

    Science.gov (United States)

    Derosa, Giuseppe; Maffioli, Pamela; Salvadeo, Sibilla A T; Ferrari, Ilaria; Ragonesi, Pietro D; Querci, Fabrizio; Franzetti, Ivano G; Gadaleta, Gennaro; Ciccarelli, Leonardina; Piccinni, Mario N; D'Angelo, Angela; Cicero, Arrigo F G

    2010-06-01

    The aim of the study was to compare the effects of the addition of sitagliptin or metformin to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state parameters. One hundred fifty-one patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA(1c)] >7.5%) in therapy with pioglitazone 30 mg/d were enrolled in this study. We randomized patients to take pioglitazone 30 mg plus sitagliptin 100 mg once a day, or pioglitazone 15 mg plus metformin 850 mg twice a day. We evaluated at baseline and after 3, 6, 9, and 12 months these parameters: body weight, body mass index, HbA(1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment beta-cell function index, fasting plasma proinsulin (Pr), Pr/FPI ratio, adiponectin, resistin (R), tumor necrosis factor-alpha (TNF-alpha), and high-sensitivity C-reactive protein. A decrease of body weight and body mass index was observed with metformin, but not with sitagliptin, at the end of the study. We observed a comparable significant decrease of HbA(1c), FPG, and PPG and a significant increase of homeostasis model assessment beta-cell function index compared with baseline in both groups without any significant differences between the 2 groups. Fasting plasma insulin, fasting plasma Pr, Pr/FPI ratio, and HOMA-IR values were decreased in both groups even if the values obtained with metformin were significantly lower than the values obtained with sitagliptin. There were no significant variations of ADN, R, or TNF-alpha with sitagliptin, whereas a significant increase of ADN and a significant decrease of R and TNF-alpha values were recorded with metformin. A significant decrease of high-sensitivity C-reactive protein value was obtained in both groups without any

  10. [Acute hypertrygliceridemic pancreatitis].

    Science.gov (United States)

    Senosiain Lalastra, Carla; Tavío Hernández, Eduardo; Moreira Vicente, Victor; Maroto Castellanos, Maite; García Sánchez, Maria Concepción; Aicart Ramos, Marta; Téllez Vivajos, Luis; Cuño Roldán, José Luis

    2013-04-01

    Acute hypertriglyceridemic pancreatitis is the third cause of acute pancreatitis in the Western population. There is usually an underlying alteration in lipid metabolism and a secondary factor. Clinical presentation is similar to that of pancreatitis of other etiologies, but the course of acute hypertriglyceridemic pancreatitis seems to be worse and more recurrent. Some laboratory data can be artefacts, leading to diagnostic errors. This is the case of amylase, which can show false low levels. Treatment is based on intense fluidotherapy and analgesia. When there is no response to conservative management, other methods to lower triglyceride levels should be used. Several options are available, such as plasmapheresis, insulin, and heparin. The present article provides a review of the current literature on this entity.

  11. Perspectives in Pancreatic Pain

    Directory of Open Access Journals (Sweden)

    A. S. Salim

    1997-01-01

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

  12. Management of necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    John Slavin1; Paula Ghaneh; Robert Sutton1; Mark Hartley; Peter Rowlands; Conall Garvey; Mark Hughes; John Neoptolemos

    2001-01-01

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

  13. Acute pancreatitis in children

    Directory of Open Access Journals (Sweden)

    Jokić Radoica

    2012-01-01

    Full Text Available Introduction. Acute pancreatitis in children is mostly due to abdominal trauma, diseases or congenital anomalies of the biliary-pancreatic tree. Both exogenous and endogenous functions of the gland could be disturbed by various levels of damage. Clinical Finding and Diagnostics. Acute abdominal pain, gastrointestinal signs and general deterioration are the main clinical findings. The examination can be completed by blood and urine tests of amylase, electrolytes level, and the C-reactive protein. In addition to these tests, ultrasound, computed tomography and endoscopy are required as well. Therapeutic Methods. The therapy of choice is non-operative treatment using medicaments to control the pain, decrease the pancreatic activity and prevent further complications. If the conservative treatment fails, the surgical approach is necessary: drainage, resections, by-pass procedures, etc. Conclusion. Acute pancreatitis is a very serious disease in childhood. Clinical experience and rational approach are very important in the diagnostic and therapeutic methods.

  14. What Is Pancreatic Cancer?

    Science.gov (United States)

    ... also called 5-HT ) or its precursor, 5-HTP. The treatment and outlook for pancreatic NETs depend ... known as precancers ). Because people are getting imaging tests such as CT scans more often than in ...

  15. Obesity and Pancreatic Cancer.

    Science.gov (United States)

    Michaud, Dominique S

    Pancreatic cancer has few known risk factors, providing little in the way of prevention, and is the most rapidly fatal cancer with 7 % survival rate at 5 years. Obesity has surfaced as an important risk factor for pancreatic cancer as epidemiological studies with strong methodological designs have removed important biases and solidified the obesity associations. Moreover, studies indicate that obesity early in adulthood is strongly associated with future risk of pancreatic cancer and that abdominal obesity is an independent risk factor. There is increasing evidence suggesting long-standing diabetes type 2 and insulin resistance are important etiological factors of this disease, providing a strong mechanistic link to obesity. The challenge remains to determine whether intended weight loss in midlife will reduce risk of pancreatic cancer and to elucidate the complex underlying pathways directly involved with risk.

  16. Tests for Pancreatic Cancer

    Science.gov (United States)

    ... from a gallstone, a tumor, or other disease). Tumor markers: Tumor markers are substances that can sometimes be found in the blood when a person has cancer. Two tumor markers may be helpful in pancreatic cancer: CA 19- ...

  17. Pancreatic Cancer Risk Factors

    Science.gov (United States)

    ... risks of other cancers (or other health problems). Examples of genetic syndromes that can cause exocrine pancreatic cancer include: Hereditary breast and ovarian cancer syndrome , caused by mutations in the BRCA1 or BRCA2 genes Familial atypical ...

  18. Characterization of pioglitazone cyclodextrin complexes: Molecular modeling to in vivo evaluation

    Science.gov (United States)

    Bramhane, Dinesh M.; Kulkarni, Preethi A.; Martis, Elvis A. F.; Pissurlenkar, Raghuvir R. S.; Coutinho, Evans C.; Nagarsenker, Mangal S.

    2016-01-01

    Aims: The objective of present study was to study the influence of different β-cyclodextrin derivatives and different methods of complexation on aqueous solubility and consequent translation in in vivo performance of Pioglitazone (PE). Material and Methods: Three cyclodextrins: β-cyclodextrin (BCD), hydroxypropyl-β-cyclodextrin (HPBCD) and Sulfobutylether-7-β-cyclodextrin (SBEBCD) were employed in preparation of 1:1 Pioglitazone complexes by three methods viz. co-grinding, kneading and co-evaporation. Complexation was confirmed by phase solubility, proton NMR, Fourier Transform Infrared spectroscopy, Differential Scanning Calorimetry (DSC) and X-Ray diffraction (XRD). Mode of complexation was investigated by molecular dynamic studies. Pharmacodynamic study of blood glucose lowering activity of PE complexes was performed in Alloxan induced diabetic rat model. Results: Aqueous solubility of PE was significantly improved in presence of cyclodextrin. Apparent solubility constants were observed to be 254.33 M–1 for BCD-PE, 737.48 M–1 for HPBCD-PE and 5959.06 M–1 for SBEBCD-PE. The in silico predictions of mode of inclusion were in close agreement with the experimental proton NMR observation. DSC and XRD demonstrated complete amorphization of crystalline PE upon inclusion. All complexes exhibited >95% dissolution within 10 min compared to drug powder that showed <40% at the same time. Marked lowering of blood glucose was recorded for all complexes. Conclusion: Complexation of PE with different BCD significantly influenced its aqueous solubility, improved in vitro dissolution and consequently translated into enhanced pharmacodynamic activity in rats PMID:27134470

  19. Characterization of pioglitazone cyclodextrin complexes: Molecular modeling to in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Dinesh M Bramhane

    2016-01-01

    Full Text Available Aims: The objective of present study was to study the influence of different β-cyclodextrin derivatives and different methods of complexation on aqueous solubility and consequent translation in in vivo performance of Pioglitazone (PE. Material and Methods: Three cyclodextrins: β-cyclodextrin (BCD, hydroxypropyl-β-cyclodextrin (HPBCD and Sulfobutylether-7-β-cyclodextrin (SBEBCD were employed in preparation of 1:1 Pioglitazone complexes by three methods viz. co-grinding, kneading and co-evaporation. Complexation was confirmed by phase solubility, proton NMR, Fourier Transform Infrared spectroscopy, Differential Scanning Calorimetry (DSC and X-Ray diffraction (XRD. Mode of complexation was investigated by molecular dynamic studies. Pharmacodynamic study of blood glucose lowering activity of PE complexes was performed in Alloxan induced diabetic rat model. Results: Aqueous solubility of PE was significantly improved in presence of cyclodextrin. Apparent solubility constants were observed to be 254.33 M–1 for BCD-PE, 737.48 M–1 for HPBCD-PE and 5959.06 M–1 for SBEBCD-PE. The in silico predictions of mode of inclusion were in close agreement with the experimental proton NMR observation. DSC and XRD demonstrated complete amorphization of crystalline PE upon inclusion. All complexes exhibited >95% dissolution within 10 min compared to drug powder that showed <40% at the same time. Marked lowering of blood glucose was recorded for all complexes. Conclusion: Complexation of PE with different BCD significantly influenced its aqueous solubility, improved in vitro dissolution and consequently translated into enhanced pharmacodynamic activity in rats

  20. Bacteriological profile of pancreatic juice in patients with chronic pancreatitis.

    Science.gov (United States)

    Parida, Salil Kumar; Pottakkat, Biju; Raja, Kalayarasan; Vijayahari, Ranjit; Lakshmi, Chandrasekharan Padma

    2014-09-28

    Information regarding the association of bacteria in the pancreatic fluid in patients with chronic pancreatitis is limited. This study was designed to analyze the prevalence of bacteria in pancreatic juice in patients with chronic pancreatitis and the association of positive pancreatic fluid culture with pre-operative and post-operative parameters. All patients with chronic pancreatitis who underwent operation from November 2011 to October 2013 were prospectively included in the study. Intra-operatively pancreatic duct fluid was collected and sent for culture sensitivity in all patients. The bacteriology of the fluid was analyzed and was correlated with preoperative, intraoperative and postoperative parameters. A total of 26 patients were analyzed. Two patients underwent endoscopic retrograde cholangio-pancreatography (ERCP) preoperatively. Bacteria was present in pancreatic duct fluid in 11 (42%) patients. Both patients who underwent ERCP had positive cultures. Most common organism observed was Escherichia coli (6/11, 55%) followed by Klebsiella pneumonia (3/11, 27%). Five patients with positive culture developed wound infection. Bacteria isolated from the wound were similar to pancreatic fluid. Bacteria is commonly present in the pancreatic juice in patients with chronic pancreatitis and its presence may have an effect on the post-operative infections following operations. Based on the pancreatic fluid culture results appropriate antibiotic can be given to the patients who will develop septic complications following surgery. Role of bacteria in the pathogenesis of the chronic calcific pancreatitis needs to be investigated in future studies.

  1. Analysis of risk factors for postoperative pancreatic fistula following pancreaticoduodenectomy.

    Science.gov (United States)

    Liu, Qi-Yu; Zhang, Wen-Zhi; Xia, Hong-Tian; Leng, Jian-Jun; Wan, Tao; Liang, Bin; Yang, Tao; Dong, Jia-Hong

    2014-12-14

    To explore the morbidity and risk factors of postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy. The data from 196 consecutive patients who underwent pancreaticoduodenectomy, performed by different surgeons, in the General Hospital of the People's Liberation Army between January 1(st), 2013 and December 31(st), 2013 were retrospectively collected for analysis. The diagnoses of POPF and clinically relevant (CR)-POPF following pancreaticoduodenectomy were judged strictly by the International Study Group on Pancreatic Fistula Definition. Univariate analysis was performed to analyze the following factors: patient age, sex, body mass index (BMI), hypertension, diabetes mellitus, serum CA19-9 level, history of jaundice, serum albumin level, blood loss volume, pancreatic duct diameter, pylorus preserving pancreaticoduodenectomy, pancreatic drainage and pancreaticojejunostomy. Multivariate logistic regression analysis was used to determine the main independent risk factors for POPF. POPF occurred in 126 (64.3%) of the patients, and the incidence of CR-POPF was 32.7% (64/196). Patient characteristics of age, sex, BMI, hypertension, diabetes mellitus, serum CA19-9 level, history of jaundice, serum albumin level, blood loss volume, pylorus preserving pancreaticoduodenectomy and pancreaticojejunostomy showed no statistical difference related to the morbidity of POPF or CR-POPF. Pancreatic duct diameter was found to be significantly correlated with POPF rates by univariate analysis and multivariate regression analysis, with a pancreatic duct diameter ≤ 3 mm being an independent risk factor for POPF (OR = 0.291; P = 0.000) and CR-POPF (OR = 0.399; P = 0.004). The CR-POPF rate was higher in patients without external pancreatic stenting, which was found to be an independent risk factor for CR-POPF (OR = 0.394; P = 0.012). Among the entire patient series, there were three postoperative deaths, giving a total mortality rate of 1.5% (3/196), and the mortality

  2. [Hereditary aspects of pancreatitis].

    Science.gov (United States)

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

    2003-01-01

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

  3. Autoantibodies in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Daniel S. Smyk

    2012-01-01

    Full Text Available Autoimmune pancreatitis (AIP was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-γ-globulinaemia, and antinuclear antibody (ANA positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis.

  4. Autoimmune pancreatitis and cholangitis

    Institute of Scientific and Technical Information of China (English)

    Niraj; Jani; James; Buxbaum

    2015-01-01

    Autoimmune pancreatitis(AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4(Ig G4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra-pancreaticmanifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG 4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG 4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings.

  5. Catfish Preservation using Porphyra Yezoensis Composites Preservatives

    Directory of Open Access Journals (Sweden)

    Zhi-Gang Qian

    2013-09-01

    Full Text Available This study aims to preserve fresh catfish meat by using Porphyra Yezoensis extract, chitosan and lactic acid Nisin. The composite preservative obtained by sensory evaluation can effectively maintain the color, odor and texture of fresh catfish meat, as well as inhibit bacterial growth. Results show that treatment using a preservative solution (Porphyra Yezoensis extract 10%, Nisin 0.2% and chitosan 15% extended the shelf life of the fresh catfish meat from 12 h to 24 h when stored at room temperature and from 6 d to 9 d when stored at 4°C. These results provide a practical method of preserving fresh catfish meat.

  6. Effects of intensive insulin therapy alone and in combination with pioglitazone on body weight, composition, distribution and liver fat content in patients with type 2 diabetes.

    Science.gov (United States)

    Shah, P K; Mudaliar, S; Chang, A R; Aroda, V; Andre, M; Burke, P; Henry, R R

    2011-06-01

    To evaluate the effects of intensive insulin therapy alone and with added pioglitazone on body weight, fat distribution, lean body mass (LBM) and liver fat in type 2 diabetic patients. Twenty-five insulin-treated, obese patients with type 2 diabetes were randomized to addition of pioglitazone 45 mg (n = 12) or placebo (n = 13) and treated intensively for 12-16 weeks. Dual-energy X-ray absorptiometry/abdominal computed tomography scans were performed before/after treatment. LBM, visceral/subcutaneous adipose tissue (VAT/SAT) and liver/spleen (L/S) attenuation ratios were measured pre-/posttreatment (a ratio insulin alone and insulin + pioglitazone significantly improved glycaemic control (7.8 ± 0.3 to 7.2 ± 0.3% and 7.6 ± 0.3 to 7.1 ± 0.4%, respectively). Body weight gain was greater with insulin + pioglitazone (4.9 ± 4.5 kg) versus insulin therapy alone (1.7 ± 0.7 kg). SAT increased significantly with pioglitazone + insulin therapy (393.9 ± 48.5 to 443.2 ± 56.7 cm(2) , p insulin therapy alone (412.9 ± 42.5 to 420.8 ± 43.8 cm(2) ). VAT decreased non-significantly in both groups (240.3 ± 41.7 to 223.8 ± 38.1 cm(2) with insulin + pioglitazone and 266.6 ± 27.4 to 250.5 ± 22.2 cm(2) with insulin therapy). LBM increased significantly by 1.92 ± 0.74 kg with insulin + pioglitazone treatment. The L/S attenuation ratio in the placebo + insulin group decreased from 1.08 ± 0.1 to 1.04 ± 0.1 (p = ns) and increased from 1.00 ± 0.1 to 1.08 ± 0.05 (p = 0.06) in the pioglitazone + insulin group. Intensification of insulin therapy in type 2 diabetic patients causes modest weight gain and no change in body fat distribution, LBM or liver fat. In contrast, the addition of pioglitazone, at equivalent glycaemia, increases weight gain, fat mass and SAT; increases LBM and tends to decrease liver fat. These changes in fat distribution may contribute to the beneficial effects of pioglitazone, despite greater weight gain. Published 2011. This article is a US Government work

  7. Pancreatic tissue fluid pressure during drainage operations for chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P

    1990-01-01

    Pancreatic tissue fluid pressure was measured in 10 patients undergoing drainage operations for painful chronic pancreatitis. The pressure was measured by the needle technique in the three anatomic regions of the pancreas before and at different stages of the drainage procedure, and the results...... a decrease in pancreatic tissue fluid pressure during drainage operations for pain in chronic pancreatitis. Regional pressure decrease were apparently unrelated to ERCP findings....

  8. Pancreatic tissue fluid pressure during drainage operations for chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P

    1990-01-01

    Pancreatic tissue fluid pressure was measured in 10 patients undergoing drainage operations for painful chronic pancreatitis. The pressure was measured by the needle technique in the three anatomic regions of the pancreas before and at different stages of the drainage procedure, and the results...... a decrease in pancreatic tissue fluid pressure during drainage operations for pain in chronic pancreatitis. Regional pressure decrease were apparently unrelated to ERCP findings....

  9. Hereditary pancreatitis and secondary screening for early pancreatic cancer.

    Science.gov (United States)

    Vitone, L J; Greenhalf, W; Howes, N R; Neoptolemos, J P

    2005-01-01

    Hereditary pancreatitis is an autosomal dominant disease with incomplete penetrance (80%), accounting for approximately 1% of all cases of pancreatitis. It is characterized by the onset of recurrent attacks of acute pancreatitis in childhood and frequent progression to chronic pancreatitis. Whitcomb et al. identified the cationic trypsinogen gene (PRSS1) on chromosome 7q35 as the site of the mutation that causes hereditary pancreatitis. The European registry of hereditary pancreatitis and familial pancreatic cancer (EUROPAC) aims to identify and make provisions for those affected by hereditary pancreatitis and familial pancreatic cancer. The most common mutations in hereditary pancreatitis are R122H, N29I and A16V but many families have been described with clinically defined hereditary pancreatitis where there is no PRSS1 mutation. It is known that the cumulative lifetime risk (to age 70 years) of pancreatic cancer is 40% in individuals with hereditary pancreatitis. This subset of individuals form an ideal group for the development of a screening programme aimed at detecting pancreatic cancer at an early stage in an attempt to improve the presently poor long-term survival. Current screening strategies involve multimodality imaging (computed tomography, endoluminal ultrasound) and endoscopic retrograde cholangiopancreatography for pancreatic juice collection followed by molecular analysis of the DNA extracted from the juice. The potential benefit of screening (curative resection) must be balanced against the associated morbidity and mortality of surgery. Philosophically, the individual's best interest must be sought in light of the latest advances in medicine and science following discussions with a multidisciplinary team in specialist pancreatic centres.

  10. Type 1 autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Zen Yoh

    2011-12-01

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

  11. NBL1 and anillin (ANLN genes over-expression in pancreatic carcinoma.

    Directory of Open Access Journals (Sweden)

    Dariusz Lange

    2009-12-01

    Full Text Available The aim of the study was to analyze the gene expression profile of pancreatic cancer to derive novel molecular markers of this malignancy. The snap-frozen or RNA-later preserved samples of 18 pancreatic adenocarcinomas, 5 chronic pancreatitis cases and 6 specimens of grossly normal pancreas were used for microarray analysis by HG-U133 Plus 2.0 oligonucleotide Affymetrix arrays. Validation was carried out by real-time quantitative PCR (Q-PCR in the set of 66 samples: 31 of pancreatic cancer, 14 of chronic pancreatitis and 21 of macroscopically unchanged pancreas. By Principal Component Analysis of the microarray data we found a very consistent expression pattern of normal samples and a less homogenous one in chronic pancreatitis. By supervised comparison (corrected p-value 0.001 we observed 11094 probesets differentiating between cancer and normal samples, while only seventy six probesets were significant for difference between cancer and chronic pancreatitis. The only gene occurring within the best 10 genes in both comparisons was S100 calcium binding protein P (S100P, already indicated for its utility as pancreatic cancer marker by earlier microarray-based studies. For validation we selected two genes which appeared as valuable candidates for molecular markers of pancreatic cancer: neuroblastoma, suppression of tumorigenicity 1 (NBL1 and anillin (ANLN. By Q-PCR, we confirmed statistically significant differences in these genes with a 9.5 fold-change difference between NBL1 expression in cancer/normal comparison and a relatively modest difference between cancer and pancreatitis. For ANLN even more distinct differences were observed (cancer/normal 19.8-fold, cancer/pancreatitis 4.0-fold. NBL1 and anillin are promising markers for pancreatic carcinoma molecular diagnostics.

  12. Pioglitazone utilization, efficacy & safety in Indian type 2 diabetic patients: A systematic review & comparison with European Medicines Agency Assessment Report

    Directory of Open Access Journals (Sweden)

    Sarayu A Pai

    2016-01-01

    Interpretation & conclusions: In India, probably due to lower dose, lower background incidence of bladder cancer and smaller sample size in epidemiological studies, association of bladder cancer with pioglitazone was not found to be significant. Reporting of CTs and adverse drug reactions to Clinical Trials Registry of India and Pharmacovigilance Programme of India, respectively, along with compliance studies with warning given in package insert and epidemiological studies with larger sample size are needed.

  13. PPAR-γ2 and PTPRD gene polymorphisms influence type 2 diabetes patients' response to pioglitazone in China

    Institute of Scientific and Technical Information of China (English)

    Qi PEI; Zhao-qian LIU; Qiong HUANG; Guo-ping YANG; Ying-chun ZHAO; Ji-ye YIN; Min SONG; Yi ZHENG; Zhao-hui MO; Hong-hao ZHOU

    2013-01-01

    Aim: To investigate the influence of peroxisome proliferator-activated receptor y2 (PPAR-Y2) gene polymorphism rs1801282 and protein tyrosine phosphatase receptor type D (PTPRD) gene polymorphism rs17584499 on the occurrence of type 2 diabetes and pioglitazone efficacy in a Chinese Han population.Methods: One hundred ninety seven type 2 diabetes patients and 212 healthy controls were enrolled.Among them,67 type 2 diabetes patients were administered pioglitazone (30 mg/d,po) for 3 months.All the subjects were genotyped for genetic variants in PPAR-γ2 and PTPRD using MALDI-TOF mass spectrometry.Fasting plasma glucose,postprandial plasma glucose,glycated hemoglobin,serum triglyceride,total cholesterol,low-density and high-density lipoprotein-cholesterol were determined.Results: The PPAR-y2 gene rs1801282 polymorphism was significantly associated with type 2 diabetes susceptibility (OR=0.515,95% CI 0.268-0.990) and the PTPRD gene rs17584499 polymorphism was also significantly associated with type 2 diabetes (OR=1.984,95% Cl 1.135-3.469) in a dominant model adjusted for age,gender and BMI.After pioglitazone treatment for 3 months,the type 2 diabetes patients with PPAR-γ2 rs1801282 CG genotypes significantly showed higher differential values of postprandial plasma glucose and serum triglyceride compared with those with rs1801282 CC genotype.The patients with PTPRD rs17584499 CT+TT genotypes showed significantly lower differential value of postprandial plasma glucose compared to those with rs17584499 CC genotype.Conclusion: Diabetes risk alleles in PPAR-y2 (rs1801282) and PTPRD (rs17584499) are associated with pioglitazone therapeutic efficacy.

  14. Altered central pain processing after pancreatic surgery for chronic pancreatitis

    NARCIS (Netherlands)

    Bouwense, S.A.W.; Ali, U. Ahmed; Broek, R.P. Ten; Issa, Y.; Eijck, C.H. van; Wilder-Smith, O.H.G.; Goor, H. van

    2013-01-01

    BACKGROUND: Chronic abdominal pain is common in chronic pancreatitis (CP) and may involve altered central pain processing. This study evaluated the relationship between pain processing and pain outcome after pancreatic duct decompression and/or pancreatic resection in patients with CP. METHODS: Pati

  15. Pancreatic ductal system obstruction and acute recurrent pancreatitis

    Institute of Scientific and Technical Information of China (English)

    M Delhaye; C Matos; M Arvanitakis; J Devière

    2008-01-01

    Acute recurrent pancreatitis is a clinical entity largely associated with pancreatic ductal obstruction.This latter includes congenital variants,of which pancreas divisum is the most frequent but also controversial,chronic pancreatitis,tumors of the pancreaticobiliary junction and sphincter of Oddi dysfunction.This review summarizes current knowledge about diagnostic work-up and therapy of these conditions.

  16. Loperamide-Induced Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Halla Vidarsdottir

    2013-01-01

    Full Text Available Acute pancreatitis is a common disease leading to hospitalizations, most often caused by gallstones or alcohol. We present a case of a patient diagnosed with acute pancreatitis considered to be due to loperamide treatment for diarrhea.

  17. Endoscopic treatment of chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Treatment of chronic pancreatitis has been exclusively surgical for a long time. Recently, endoscopic therapy has become widely used as a primary therapeutic option.Initially performed for drainage of pancreatic cysts and pseudocysts, endoscopic treatments were adapted to biliary and pancreatic ducts stenosis. Pancreatic sphincterotomy which allows access to pancreatic ducts was firstly reported. Secondly, endoscopic methods of stenting, dilatation, and stones extraction of the bile ducts were applied to pancreatic ducts. Nevertheless,new improvements were necessary: failures of pancreatic stone extraction justified the development of extra-corporeal shock wave lithotripsy; dilatation of pancreatic stenosis was improved by forage with a new device; moreover endosonography allowed guidance for celiac block, gastro-cystostomy, duodeno-cystostomy and pancreatico-gastrostomy. Although endoscopic treatments are more and more frequently accepted,indications are still debated.

  18. [The epidemiology of pancreatic cancer].

    Science.gov (United States)

    Lakatos, Gábor; Tulassay, Zsolt

    2010-10-31

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

  19. Pancreatic disorders and diabetes mellitus.

    Science.gov (United States)

    Meisterfeld, R; Ehehalt, F; Saeger, H D; Solimena, M

    2008-09-01

    Diabetes mellitus is a common disease among patients with pancreatic cancer and chronic pancreatitis, disorders of the exocrine pancreas. Different clinical features of diabetes are associated with these two conditions: hyperinsulinemia and peripheral insulin resistance are the prevailing diabetic traits in pancreatic cancer, whereas reduced islet cell mass and impaired insulin secretion are typically observed in chronic pancreatitis. Whether or not a causal relationship exists between diabetes and pancreatic carcinoma is an intriguing but unanswered question. Diabetes often precedes pancreatic cancer and is thus regarded as a potential risk factor for malignancy. Conversely, pancreatic cancer may secrete diabetogenic factors. Given these findings, there is increasing interest in whether close monitoring of the glycemic profile may aid early detection of pancreatic tumor lesions.

  20. Pancreatic trauma: A concise review

    Science.gov (United States)

    Debi, Uma; Kaur, Ravinder; Prasad, Kaushal Kishor; Sinha, Saroj Kant; Sinha, Anindita; Singh, Kartar

    2013-01-01

    Traumatic injury to the pancreas is rare and difficult to diagnose. In contrast, traumatic injuries to the liver, spleen and kidney are common and are usually identified with ease by imaging modalities. Pancreatic injuries are usually subtle to identify by different diagnostic imaging modalities, and these injuries are often overlooked in cases with extensive multiorgan trauma. The most evident findings of pancreatic injury are post-traumatic pancreatitis with blood, edema, and soft tissue infiltration of the anterior pararenal space. The alterations of post-traumatic pancreatitis may not be visualized within several hours following trauma as they are time dependent. Delayed diagnoses of traumatic pancreatic injuries are associated with high morbidity and mortality. Imaging plays an important role in diagnosis of pancreatic injuries because early recognition of the disruption of the main pancreatic duct is important. We reviewed our experience with the use of various imaging modalities for diagnosis of blunt pancreatic trauma. PMID:24379625

  1. General Information about Pancreatic Cancer

    Science.gov (United States)

    ... Treatment Research Pancreatic Cancer Treatment (PDQ®)–Patient Version General Information About Pancreatic Cancer Go to Health Professional ... lies between the stomach and the spine . Enlarge Anatomy of the pancreas. The pancreas has three areas: ...

  2. Expression of REST4 in human gliomas in vivo and influence of pioglitazone on REST in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Huan [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China); Gao, Zhangfeng [Department of Neurosurgery, Second Xiangya Hospital of Central South University, Changsha 410008 (China); Wu, Nayiyuan; Zeng, Liu; Tang, Xinyue; Chen, Xiaoping; Liu, Zhaoqian; Zhang, Wei; Wang, Liansheng [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China); Li, Zhi, E-mail: lizhi489@163.com [Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008 (China); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078 (China)

    2015-08-07

    The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) has an irreplaceable role during the differentiation of neurons. REST has multiple splice variants which link to various types of cancer. Previous work had highlighted the role of REST in glioma, where the expression of REST is enhanced. But whether alternative splicing of REST is expressed in glioma has not been described. Here, we show that a specific isoform REST4 is expressed in glioma specimens, and will influence the mRNA level of REST in vivo. Peroxisome proliferator-activated receptor-γ (PPARγ) agonists have a role of antineoplastic in various tumor cells, which including glioma cells. Moreover, study indicated that PPARγ agonist pioglitazone can promote alternative splicing of REST pre-mRNA. In this study, we selected pioglitazone as a tool drug to explore whether the role of pioglitazone in anti-glioma is mediated by regulating REST expression or promoting alternative splicing of REST in glioma cells. Results show that pioglitazone can inhibit proliferation and induce apoptosis of glioma cell in vitro, which may be mediated by down-regulating REST mRNA level but not by inducing alternative splicing of REST pre-mRNA. Our study firstly reports the expression of REST4 in glioma tissue samples. And we recommend that pioglitazone, which can reduce the expression level of REST, represents a promising drug for therapy of glioma. - Highlights: • A specific isoform REST4 is expressed in glioma specimens in vivo. • REST4 will influence the mRNA level of REST in vivo. • Pioglitazone can inhibit proliferation and induce apoptosis of glioma cells. • The role of pioglitazone in anti-glioma may be mediated by down-regulating REST.

  3. Adiponectin gene polymorphism rs2241766 T/G is associated with response to pioglitazone treatment in type 2 diabetic patients from southern China.

    Directory of Open Access Journals (Sweden)

    Hong Yang

    Full Text Available INTRODUCTION: Insulin sensitizing drugs such as pioglitazone are not uniformly treatment effective among individual type 2 diabetic patients. Here, the relationship of pioglitazone efficacy to single nucleotide polymorphisms (SNP of the adiponectin gene, a critical gene directly regulated by the drug, was examined in a cohort of Chinese Han type 2 diabetic patients. METHODS: Eighty type 2 diabetic patients were treated with pioglitazone (15 mg/day for 12 weeks without interruption of their current therapeutic regimen. Fasting plasma glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR, and glycated hemoglobin (HbA1c% were collected both prior to and following pioglitazone treatment. Response to pioglitazone was defined as a decrease of at least 15% in HbA1c% levels. Three regions of the adiponectin gene containing SNPs (promoter, intron 2 and exon 2, and exon 3 were amplified and sequenced to determine genotype. RESULTS: Serum adiponectin levels were significantly increased (p<0.001 whereas fasting plasma glucose, fasting insulin, HOMA-IR, and HbA1c% values were significantly decreased relative to baseline measurements (p<0.001. Response of patients with TG and TT genotypes at rs2241766 (exon2; 52.9% vs. 12.7%, respectively p = 0.001 was statistically significant relative to all other patients. Amongst rs2241766 TG and TT patients, the mean decrease in HbA1c% levels was greater where the genotype was TG (1.15±0.80 vs. 0.52±0.64, p = 0.001. CONCLUSIONS: The adiponectin gene polymorphism rs2241766 T/G is associated with pioglitazone efficacy in type 2 diabetic patients, and status of the polymorphism may be an important clinical factor to consider prior to pioglitazone treatment.

  4. Pioglitazone inhibits the expression of nicotinamide adenine dinucleotide phosphate oxidase and p38 mitogen-activated protein kinase in rat mesangial cells

    Institute of Scientific and Technical Information of China (English)

    WANG Shan; YE Shan-dong; SUN Wen-jia; HU Yuan-yuan

    2013-01-01

    Background Oxidative Stress and p38 mitogen-activated protein kinase (p38MAPK) play a vital role in renal fibrosis.Pioglitazone can protect kidney but the underlying mechanisms are less clear.The purpose of this study was to investigate the effect of pioglitazone on oxidative stress and whether the severity of oxidative stress was associated with the phosphorylation level of p38MAPK.Methods Rat mesangial cells were cultured and randomly assigned to control group,high glucose group and pioglitazone group.After 48-hour exposure,the supernatants and ceils were collected.The protein levels of p22phox,p47phox,phosphorylated p38MAPK,total p38MAPK were measured by Western blotting.The gene expressions of p22phox,p47phox were detected by RT-PCR.The levels of intracellular reactive oxygen species (ROS) were determined by flow cytometry.The levels of superoxide dismutase (SOD) and maleic dialdehyde (MDA) in the supernatant were determined respectively.Results Compared with the control group,the expression levels of p22phox,p47phox,phospho-p38 and ROS significantly increased,activity of SOD decreased in high glucose group,while the level of MDA greatly increased (P <0.01).Pioglitazone significantly suppressed p22phox,p47phox expressions and oxidative stress induced by high glucose.The expressions of p22phox,p47phox,phospho-p38MAPK and ROS generation were markedly reduced after pioglitazone treatment (P <0.05).The activity of SOD in the the supernatant increased (P <0.05),while the level of MDA decreased greatly by pioglitazone (P <0.05).The level of oxidative stress was associated with the phosphorylation level of p38MAPK (P <0.01).Conclusion Pioglitazone can inhibit oxidative stress through suppressing NADPH oxidase expression and p38MAPK phosphorylation.

  5. The Effects of Sub-Chronic Treatment with Pioglitazone on the Septic Mice Mortality in the Model of Cecal Ligation and Puncture: Involvement of Nitric Oxide Pathway

    Directory of Open Access Journals (Sweden)

    Hamed Shafaroodi

    2015-10-01

    Full Text Available Sepsis is a systemic inflammatory response syndrome caused by an infection and remains as a major challenge in health care. Many studies have reported that pioglitazone may display anti-inflammatory effects. This study was designed to evaluate the effect of subchronic treatment with pioglitazone on high-grade septic mice survival and nitrergic system involvement. Diffused sepsis was induced by cecal ligation and puncture (CLP surgery in male NMRI mice (20-30 g. Pioglitazone (5,10 and 20 mg/kg was administered by gavage daily for 5 days prior to surgery. Nitric oxide involvement was assessed by sub-chronic administration of a non-selective nitric oxide synthase inhibitor, L-NAME and a selective inducible nitric oxide synthase inhibitor, aminoguanidine. TNF-α  and IL-1β plasma levels were measured by ELISA. Pioglitazone (10 and 20 mg/kg significantly improved survival rate in septic mice. The chronic intraperitoneally co-administration of L-NAME (0.5 mg/kg, daily or aminoguanidine (1 mg/kg, daily with a daily dose of pioglitazone, 5 mg/kg, significantly increased the survival rate. This survival improving effect was accompanied by a significant reduction in pro-inflammatory cytokines TNF-α and IL-1β plasma levels. In conclusion, sub-chronic pioglitazone treatment can improve survival in mouse sepsis model by CLP. Inhibition of nitric oxide release, probably through inducible nitric oxide synthase at least in part is responsible for this effect. Suppression of TNF-α and IL-1β could be another mechanism in pioglitazone-induced survival improving effect in septic mice.

  6. The Effects of Sub-Chronic Treatment with Pioglitazone on the Septic Mice Mortality in the Model of Cecal Ligation and Puncture: Involvement of Nitric Oxide Pathway.

    Science.gov (United States)

    Shafaroodi, Hamed; Hassanipour, Mahsa; Mousavi, Zahra; Rahimi, Nastaran; Dehpour, Ahmad Reza

    2015-10-01

    Sepsis is a systemic inflammatory response syndrome caused by an infection and remains as a major challenge in health care. Many studies have reported that pioglitazone may display anti-inflammatory effects. This study was designed to evaluate the effect of subchronic treatment with pioglitazone on high-grade septic mice survival and nitrergic system involvement. Diffused sepsis was induced by cecal ligation and puncture (CLP) surgery in male NMRI mice (20-30 g). Pioglitazone (5,10 and 20 mg/kg) was administered by gavage daily for 5 days prior to surgery. Nitric oxide involvement was assessed by sub-chronic administration of a non-selective nitric oxide synthase inhibitor, L-NAME and a selective inducible nitric oxide synthase inhibitor, aminoguanidine. TNF-α  and IL-1β plasma levels were measured by ELISA. Pioglitazone (10 and 20 mg/kg) significantly improved survival rate in septic mice. The chronic intraperitoneally co-administration of L-NAME (0.5 mg/kg, daily) or aminoguanidine (1 mg/kg, daily) with a daily dose of pioglitazone, 5 mg/kg, significantly increased the survival rate. This survival improving effect was accompanied by a significant reduction in pro-inflammatory cytokines TNF-α and IL-1β plasma levels. In conclusion, sub-chronic pioglitazone treatment can improve survival in mouse sepsis model by CLP. Inhibition of nitric oxide release, probably through inducible nitric oxide synthase at least in part is responsible for this effect. Suppression of TNF-α and IL-1β could be another mechanism in pioglitazone-induced survival improving effect in septic mice.

  7. [Impact of the 2016 new definition and classification system of pancreatic fistula on the evaluation of pancreatic fistula after pancreatic surgery].

    Science.gov (United States)

    Han, X L; Xu, J; Wu, W M; Dai, M H; Zhang, T P; Liao, Q; Chen, G; Guo, J C; Wang, W B; Cong, L; Zhao, Y P

    2017-07-01

    Objective: To discuss the impact of updated definition and classification system of pancreatic fistula published in 2016 on the postoperative classification of pancreatic fistula. Methods: Retrospective analysis was made on patients who underwent pancreatic surgery at ward 1 in Department of General Surgery, Peking Union Medical College Hospital from January 2015 to December 2016.A total of 408 patients were included in this retrospective study, male/female was 184/224, aged from 9 to 81 years with mean age of 51.6 years.One hundred and fifty-two cases were performed pancreaticoduodenectomy, 125 cases for distal pancreatectomy, 43 cases for spleen preservation distal pancreatectomy, 61 cases for partital pancreatectomy or enucleation, 8 cases for middle pancreatectomy, 6 cases for pancreaticojejunostomy and 13 cases for other procedures.Clinical data including postoperative drainage fluid volume, amylase concentration, duration of hospitalization and drainage were obtained, revaluated and re-analyzed, classified grounded on 2005 edition and 2016 edition, respectively.t-test was adopted for data analysis. Results: According to the previous standards, the incident rate of pancreatic fistula was 57.4%, and the incident rate of B-level plus C-level pancreatic fistula was 35.8%, which decreased to 13.7% based on 2016 edition.Nine patients who received percutaneous puncture or endoscopic drainage was regraded from C-level to B-level. The average duration of postoperative hospitalization of patients without pancreatic fistula was (12.5±6.0)days, demonstrating no significant difference compared to (14.1±7.7)days, duration of postoperative hospitalization of A-level(under 2005 edition of criteria) pancreatic fistula group(t=1.66, P=0.09) and (12.4±6.1)days, duration of postoperative hospitalization of biochemical leakage group(t=0.14, P=0.89). Nevertheless, there was statistical significant difference between the average postoperative duration of hospitalization(30.7±16

  8. CT of pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Toshio (Nagasaki Univ. (Japan). School of Medicine)

    1990-09-01

    One hundred and two cases of acute and chronic pancreatitis were studied by computed tomography. Fluid collection was detected by CT in 45 cases, and the common extrapancreatic sites of involvement included the lesser sac (13 cases), anterior pararenal space (9 cases), transverse mesocolon (7 cases) and posterior pararenal space (5 cases). Ten cases of spontaneous resolution of pancreatic pseudocysts were encountered. Cystojejunostomy was done on 6 patients. A 4-to-6-weeks time interval has been currently accepted as necessary for pseudocyst wall maturation. However, the surgery was not possible in two patients in this series since the cyst wall was too thin. It is considered that the time over 3 months is required for surgical anastomosis of the cyst to the gastrointestinal tract. Pancreatic abscess has become the most common cause of death from pancreatitis. In this series pancreatic abscess occurred in 8 patients. Gas collection in the pancreas was observed in only one patient. In the other patients, pseudocysts had become infected and converted to abscesses. The CT number of 4 infected pseudocysts was less than 15 HU. Thus, it was not possible to distinguish infected from noninfected pseudocysts by CT. The author studied 9 patients with focal inflammatory mass of the pancreas with histologically proved severe fibrosis. All masses were small. Angiography showed occlusion or marked stenosis of the splenic vein in 3 cases. The postcontract CT (after intravenous bolus injection) in 7 cases of focal inflammatory mass demonstrated almost equal enhanced effect of the mass as compared with the adjacent normal pancreatic parenchyma. This finding is considered to be useful in distinguishing inflammatory mass from pancreatic carcinoma. (author).

  9. Pioglitazone does not increase the risk of type II diabetes in patients with bladder cancer: A retrospective study.

    Science.gov (United States)

    Dong, Youhong; Wang, Anping

    2016-07-01

    The aim of the retrospective study was to analyze the effect of pioglitazone on the expression of tumor tissue inflammation factor interleukin (IL)-8, macrophage colony-stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF) of type II diabetes in bladder cancer patients. In addition, whether there was a correlation between pioglitazone and the occurrence of male bladder cancer was also investigated. In total, 42 male cases diagnosed with type II diabetes secondary to bladder cancer were selected. Forty male cases, with simplex type II diabetes but not with bladder cancer, served as the control. Tumor biopsy specimens were collected to detect the expression levels of IL-8, M-CSF and VEGF. The results showed that the expression of IL-8, M-CSF and VEGF of the simplex diabetes group was significantly lower than that of the secondary to tumor group (Ppioglitazone, duration of diabetes, average fasting blood sugar and glycated hemoglobin levels, was not statistically significant. Multivariable logistic regression analysis revealed that the expression levels of IL-8, M-CSF and VEGF were independent risk factors for the occurrence of bladder cancer (Ppioglitazone (P>0.05). In conclusion, oral pioglitazone may not increase the risk of type II diabetes patients with bladder cancer. However, the occurrence of bladder cancer be associated with the increasing expression levels of IL-8, M-CSF and VEGF.

  10. Formulation and evaluation of sustained release matrix tablets of pioglitazone hydrochloride using processed Aloe vera mucilage as release modifier

    Directory of Open Access Journals (Sweden)

    Manoj Choudhary

    2015-01-01

    Full Text Available Background: Natural gums and mucilage which hydrates and swells on contact with aqueous media are used as additives in the formulation of hydrophilic drug delivery system. Aim: The purpose of this study was to develop a new monolithic matrix system for complete delivery of Pioglitazone hydrochloride (HCl, in a zero-order manner over an extended time period using processed Aloe vera gel mucilage (PAG as a release modifier. Materials and Methods: The matrices were prepared by dry blending of selected ratios of polymer and ingredients using direct compression technique. Physicochemical properties of dried powdered mucilage of A. vera were studied. Various formulations of pioglitazone HCl and A. vera mucilage were prepared using different drug: Polymer ratios viz., 1:1, 1:2, 1:3, 1:4, 1:5 for PAG by direct compression technique. Results: The formulated matrix tablets were found to have better uniformity of weight and drug content with low statistical deviation. The swelling behavior and in vitro release rate characteristics were also studied. Conclusion: The study proved that the dried A. vera mucilage can be used as a matrix forming material for controlled release of Pioglitazone HCl matrix tablets.

  11. Incretin hormones and beta cell function in chronic pancreatitis

    DEFF Research Database (Denmark)

    Knop, Filip Krag

    2010-01-01

    . It is unknown whether the incretin defect is a primary event leading to T2DM or arises as a consequence of the diabetic state. To investigate this we studied patients with chronic pancreatitis (CP). Over time, CP leads to secondary diabetes mellitus (DM). If patients with CP and secondary DM exhibit...... independently of the endocrine status of patients with CP, the incretin defect could represent a primary pathogenetic defect. Three protocols have been employed to investigate this. In a study investigating postprandial incretin responses in 8 patients with CP and exocrine pancreatic insufficiency......, with and without pancreatic enzyme supplementation (PES), we observed preserved incretin responses as compared to matched healthy subjects; and, further, that PES increased postprandial incretin responses in these patients. This suggests not only that the secretion of incretin hormones is regulated by the mere...

  12. Isolated Pediatric Pancreatic Transection Secondary to Ocean-Related Trauma

    Directory of Open Access Journals (Sweden)

    Afif N Kulaylat

    2013-03-01

    Full Text Available Context Isolated pancreatic transection is a rare but well-recognized complication following blunt trauma of the abdomen. Diagnosis at presentation may be difficult and delayed due to subtle initial symptoms and evolving nature of the injury. Case report We describe an isolated complete pancreatic transection in a 14-year-old female secondary to a previously unreported and highly unusual mechanism (being tossed by a wave. Diagnosis was obtained by computed tomography scan 24 hours following initial trauma. She was managed operatively with an open distal pancreatectomy with splenic preservation and no subsequent complications. Conclusions The force sustained from the blunt abdominal trauma of being tossed by a wave can be significant. The management of pancreatic injuries in children, particularly in the context of ductal transection, is controversial. Timely recognition and management is critical to optimal outcomes. Early operative intervention may help to avoid complications such as abscess or pseudocyst formation.

  13. Acute Pancreatitis Associated with Ifosfamide

    Directory of Open Access Journals (Sweden)

    Miao-Chiu Hung

    2007-04-01

    Full Text Available Acute pancreatitis is a rare complication during chemotherapy for pediatric patients with solid tumors. We report a 9-year-old boy with osteosarcoma who experienced 2 episodes of pancreatitis 1 day and 48 days after infusion of ifosfamide (IFOS, respectively. From a MEDLINE search, this is the 3rd reported case and 2nd reported pediatric case of IFOS-induced pancreatitis, and only this case experienced late-onset pancreatitis.

  14. Brain Metastasis in Pancreatic Cancer

    OpenAIRE

    Marko Kornmann; Doris Henne-Bruns; Jan Scheele; Christian Rainer Wirtz; Thomas Kapapa; Johannes Lemke

    2013-01-01

    Pancreatic cancer is a fatal disease with a 5-year survival rate below 5%. Most patients are diagnosed at an advanced tumor stage and existence of distant metastases. However, involvement of the central nervous system is rare in pancreatic cancer. We retrospectively analyzed all cases of brain metastases in pancreatic cancer reported to date focusing on patient characteristics, clinical appearance, therapy and survival. Including our own, 12 cases of brain metastases originating from pancreat...

  15. Middle-Preserving Pancreatectomy: An Interesting Procedure for Pancreas-Sparing Resection

    Directory of Open Access Journals (Sweden)

    Cosimo Sperti

    2010-05-01

    Full Text Available Context Total pancreatectomy is the treatment of choice for multicentric diseases involving the head and the body-tail of the pancreas. Middle-preserving pancreatectomy is a recently reported alternative procedure when the pancreatic body is spared from disease. We report on the successful preservation of the pancreatic body in a patient harboring a multicentric intraductal papillary mucinous neoplasia (IPMN. Case report A multicentric IPMN was diagnosed in a 59-year-old man. A standard pylorus preserving pancreaticoduodenectomy was performed, followed by a spleen-preserving distal pancreatectomy. The splenic vessels were carefully preserved. The residual 5 cm of the pancreatic body were anastomosed to the jejunum after verifying that the resection line on both sides was negative at frozen section examination. The postoperative course was complicated by transient peritoneal bleeding managed with angiographic embolization of the splenic artery. A borderline mixed type IPMN of the head and chronic pancreatitis of the tail were found at pathological examination. Eleven months after surgery, the patient is well and disease free; glycemic control is achieved by diet. Conclusion A middle-preserving pancreatectomy can be performed safely for multicentric IPMNs involving the head and the body-tail of the gland. It can prevent problems with the glycemic control that usually follows total pancreatectomy.

  16. Genetic basis of chronic pancreatitis

    NARCIS (Netherlands)

    Jansen, JBMJ; Morsche, RT; van Goor, Harry; Drenth, JPH

    2002-01-01

    Background: Pancreatitis has a proven genetic basis in a minority of patients. Methods: Review of the literature on genetics of pancreatitis. Results: Ever since the discovery that in most patients with hereditary pancreatitis a mutation in the gene encoding for cationic trypsinogen (R122H) was

  17. Drug-induced acute pancreatitis

    NARCIS (Netherlands)

    I.A. Eland (Ingo)

    2003-01-01

    textabstractAcute pancreatitis is an inflammatory disease of the pancreas with sudden onset. The severity of acute pancreatitis may vary from mild to life threatening. There are many risk factors for acute pancreatitis, among which gallstones and alcohol abuse are most widely known. Drugs are

  18. Drug-induced acute pancreatitis

    NARCIS (Netherlands)

    I.A. Eland (Ingo)

    2003-01-01

    textabstractAcute pancreatitis is an inflammatory disease of the pancreas with sudden onset. The severity of acute pancreatitis may vary from mild to life threatening. There are many risk factors for acute pancreatitis, among which gallstones and alcohol abuse are most widely known. Drugs are consid

  19. Genetic basis of chronic pancreatitis

    NARCIS (Netherlands)

    Jansen, JBMJ; Morsche, RT; van Goor, Harry; Drenth, JPH

    2002-01-01

    Background: Pancreatitis has a proven genetic basis in a minority of patients. Methods: Review of the literature on genetics of pancreatitis. Results: Ever since the discovery that in most patients with hereditary pancreatitis a mutation in the gene encoding for cationic trypsinogen (R122H) was foun

  20. Vaginal metastasis of pancreatic cancer.

    Science.gov (United States)

    Benhayoune, Khadija; El Fatemi, Hinde; El Ghaouti, Meryem; Bannani, Abdelaziz; Melhouf, Abdelilah; Harmouch, Taoufik

    2015-01-01

    Vaginal metastasis from pancreatic cancer is an extreme case and often indicates a poor prognosis. We present a case of pancreatic carcinoma with metastasis to the vagina that was discovered by vaginal bleeding. To our knowledge, this is the third case in the world of a primary pancreatic adenocarcinoma discovered of symptoms from a vaginal metastasis.

  1. Chronic pancreatitis in dogs.

    Science.gov (United States)

    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.

  2. Autoantibodies in chronic pancreatitis

    DEFF Research Database (Denmark)

    Rumessen, J J; Marner, B; Pedersen, N T

    1985-01-01

    In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane, and reti......In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane......, and reticulin, and the IgG- and IgA-type pancreas-specific antibodies against islet cells, acinus cells, and ductal cells (DA) were estimated blindly. In 23 of the patients chronic pancreatitis was verified, whereas chronic pancreatitis was rejected in 37 patients (control group). IgG and IgA were found...... in significantly higher concentrations in the patients with chronic pancreatitis than in the control group but within the normal range. ANA and DA occurred very frequently in both groups but with no statistical difference. Other autoantibodies only occurred sporadically. The findings of this study do not support...

  3. Hepatobiliary and pancreatic ascariasis

    Science.gov (United States)

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S

    2016-01-01

    Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease. PMID:27672273

  4. Hepatobiliary and pancreatic ascariasis.

    Science.gov (United States)

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S

    2016-09-07

    Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease.

  5. Hypoglycaemia with oral antidiabetic drugs: results from prescription-event monitoring cohorts of rosiglitazone, pioglitazone, nateglinide and repaglinide.

    Science.gov (United States)

    Vlckova, Veronika; Cornelius, Victoria; Kasliwal, Rachna; Wilton, Lynda; Shakir, Saad A W

    2009-01-01

    Hypoglycaemia is an acute complication associated with intensive treatment of patients with diabetes mellitus. This complication poses a major challenge in diabetes management. Furthermore, severe hypoglycaemia may be life threatening. Although hypoglycaemia is more often associated with insulin treatment, oral hypoglycaemic agents have the potential to trigger hypoglycaemia. The aim of this study was to quantify the incidence of hypoglycaemic events and to describe the pattern of these incident events during the first 9 months of treatment with four oral antidiabetic drugs, rosiglitazone, pioglitazone, nateglinide and repaglinide, prescribed in general practice in England. We used data collected for prescription-event monitoring (PEM) studies of rosiglitazone, pioglitazone, nateglinide and repaglinide. PEM is an observational, non-interventional, incept cohort study. Observation time for each patient and incidence rate (IR) per 1000 patient-years of treatment for hypoglycaemia was calculated for each drug cohort. Smoothed hazard estimates were plotted over time. Case/non-case analysis was performed to describe and compare patients who had at least one hypoglycaemic event in the first 9 months of treatment with those who did not. The total number of patients included in the analysis was 14,373, 12,768, 4,549 and 5,727 in rosiglitazone, pioglitazone, nateglinide and repaglinide cohorts, respectively. From these, 276 patients experienced at least one episode of hypoglycaemia. The IR was between 50% and 100% higher in patients receiving treatment with meglitinides compared with those treated with the thiazolidinediones (TZDs) [IR = 9.94, 9.64, 15.71 and 20.32 per 1,000 patient-years for rosiglitazone, pioglitazone, nateglinide and repaglinide, respectively]. The plot of the hazard function and the estimated shape parameter from the Weibull regression model showed that pioglitazone, nateglinide and repaglinide had non-constant (decreasing) hazards over time, whereas

  6. Primary Pancreatic Head Tuberculosis: Great Masquerader of Pancreatic Adenocarcinoma

    Science.gov (United States)

    Gupta, Dhaval; Patel, Jatin; Rathi, Chetan; Ingle, Meghraj; Sawant, Prabha

    2015-01-01

    Isolated pancreatic tuberculosis (TB) is considered an extremely rare condition, even in the developing countries. Most reported cases of pancreatic TB are diagnosed after exploratory laparotomy or autopsy. Pancreatic TB is a potential mimic of invasive pancreatic malignancy and the presence of vascular invasion does not distinguish one condition from the other. Every effort should be made for the earliest diagnosis of this condition as TB is a treatable condition and it avoids unnecessary management of pancreatic carcinoma. Here we report a rare case of primary pancreatic head TB in a 58-year-old male who presented with hypodense lesion in head of pancreas with double duct sign and portal vein invasion mimicking non-resectable pancreatic carcinoma. PMID:27785295

  7. Efficacy of pioglitazone on glycemic control and carotid intima-media thickness in type 2 diabetes patients with inadequate insulin therapy.

    Science.gov (United States)

    Yasunari, Eisuke; Takeno, Kageumi; Funayama, Hideaki; Tomioka, Setsuko; Tamaki, Motoyuki; Fujitani, Yoshio; Kawamori, Ryuzo; Watada, Hirotaka; Hirose, Takahisa

    2011-01-24

    Aims/Introduction:  The present study was designed to determine the effects of pioglitazone on glycemic control and atherosclerosis in patients with poorly controlled type 2 diabetes on insulin therapy.   The study was a prospective, randomized controlled trial involving 48 patients with inadequately controlled type 2 diabetes treated with insulin. We assigned patients to oral pioglitazone titrated from 15-30 mg (n = 22) or no pioglitazone (n = 26), to be taken in addition to their glucose-lowering drugs and other medications. Daily insulin doses and numbers were recorded during the study period.   The adjusted mean glycosylated hemoglobin (HbA1c) values decreased significantly by 1.13 ± 1.50% and 0.55 ± 0.76% in the pioglitazone and control groups, respectively. Significant decrease of HbA1c level was observed in the pioglitazone group compared with the control group (P < 0.05). The insulin dose lowered by 0.04 ± 0.10 units/kg/day in the pioglitazone group and increased by 0.03 ± 0.10 units/kg/day in the control group (P < 0.05). The number of insulin injections decreased by 0.1 ± 0.6 times/day in the pioglitazone group and increased by 0.2 ± 0.4 times/day in the control group (P < 0.05). The carotid intima-media thickness estimated by B-mode echography was carried out in both groups and decreased significantly at the end-point only in the pioglitazone group, relative to the baseline.   These findings show that pioglitazone is useful in improving glycemic control and preventing the progression of atherosclerosis in poorly-controlled type 2 diabetics on insulin therapy. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00064.x, 2010).

  8. Three-month treatment with pioglitazone reduces circulating C1q-binding adiponectin complex to total-adiponectin ratio, without changes in body mass index, in people with type 2 diabetes.

    Science.gov (United States)

    Nakatsuji, Hideaki; Kishida, Ken; Kobayashi, Hironori; Funahashi, Tohru; Shimomura, Iichiro

    2013-01-01

    We measured circulating C1q-binding adiponectin (C1q-APN) levels before and after 3-month treatment with pioglitazone in people with type 2 diabetes. The results indicate 3-month treatment with pioglitazone reduces circulating levels of C1q-APN/total-adiponectin ratio without changes in body mass index.

  9. The clinical assessment of intraductal ultrasonography in the differential diagnosis of pancreatic carcinoma and chronic pancreatitis.

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To assess and compare the clinical value of intraductal ultrasonography (IDUS) in the differential diagnosis of pancreatic carcinoma and chronic pancreatitis with conventional imaging methods. Methods: IDUS was carried out in eighteen patients with pancreatic carcinoma and chronic pancreatitis

  10. Pioglitazone Upregulates Angiotensin Converting Enzyme 2 Expression in Insulin-Sensitive Tissues in Rats with High-Fat Diet-Induced Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2014-01-01

    Full Text Available Background and Aim. Thiazolidinediones (TZDs can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH. Angiotensin (Ang II, the primary effector of renin-angiotensin system (RAS, plays vital roles in the development and progression of NASH. And some AngII-mediated effects can be regulated by TZDs. Angiotensin-converting enzyme (ACE 2, a new component of RAS, can degrade Ang II to attenuate its subsequent physiological actions. We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats. Methods. Forty rats were divided into the normal control, high-fat diet (HFD, pioglitazone control, and HFD plus pioglitazone groups. After 24 weeks of treatment, we evaluated changes in liver histology and tissue-specific ACE2 expression. Results. ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group. Conclusions. Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues.

  11. Leptin replacement improves postprandial glycemia and insulin sensitivity in human immunodeficiency virus-infected lipoatrophic men treated with pioglitazone: a pilot study.

    Science.gov (United States)

    Magkos, Faidon; Brennan, Aoife; Sweeney, Laura; Kang, Eun Seok; Doweiko, John; Karchmer, Adolf W; Mantzoros, Christos S

    2011-07-01

    Highly active antiretroviral therapy (HAART)-induced lipoatrophy is characterized by hypoleptinemia and insulin resistance. Evidence suggests that pioglitazone and recombinant methionyl human leptin (metreleptin) administration has beneficial effects in human immunodeficiency virus (HIV)-infected lipoatrophic patients. This proof-of-concept study aimed at evaluating whether the combination of metreleptin and pioglitazone has favorable effects, above and beyond pioglitazone alone, on both metabolic outcomes and peripheral lipoatrophy in HIV-infected patients on HAART. Nine HIV-positive men with at least 6 months of HAART exposure, clinical evidence of lipoatrophy, and low leptin concentrations (≤4 ng/mL) were placed on pioglitazone treatment (30 mg/d per os) and were randomized to receive either metreleptin (0.04 mg/kg subcutaneously once daily; n = 5) or placebo (n = 4) for 3 months in a double-blinded fashion. Compared with placebo, metreleptin reduced fasting serum insulin concentration, increased adiponectin concentration, reduced the homeostasis model assessment index of insulin resistance, and attenuated postprandial glycemia in response to a mixed meal (all P ≤ .02), but did not affect trunk and peripheral fat mass. HIV control was not affected, and no major adverse effects were observed. Metreleptin administration in HIV-positive, leptin-deficient patients with lipoatrophy treated with pioglitazone improves postprandial glycemia and insulin sensitivity. Results from this pilot study should be confirmed in larger clinical trials.

  12. Risk of cardiovascular disease and all-cause mortality among diabetic patients prescribed rosiglitazone or pioglitazone: a meta-analysis of retrospective cohort studies

    Institute of Scientific and Technical Information of China (English)

    CHEN Xin; YANG Li; ZHAI Suo-di

    2012-01-01

    Background The difference of cardiovascular effects between rosiglitazone and pioglitazone treatment for diabetic patients has not been thoroughly studied.We performed a meta-analysis to compare the risk of cardiovascular adverse effects in patients with type 2 diabetes treated with rosiglitazone compared to pioglitazone.Methods The Cochrane Library,PubMed,and Embase were searched to identify retrospective cohort studies assessing cardiovascular outcomes with rosiglitazone and pioglitazone.Meta-analysis of retrospective cohort studies was conducted using RevMan 5.0 software to calculate risk ratios.Results Of the 74 references identified,eight studies involving 945 286 patients fit the inclusion criteria for the analysis.The results of meta-analyses showed that,compared with pioglitazone,rosiglitazone therapy significantly increased the risk of myocardial infarction (risk ratios (RR) 1.17,95% confidence interval (CI) 1.04-1.32; P=0.01),the risk of heart failure (RR 1.18,95% CI 1.02-1.36; P=0.03),and total mortality (RR 1.13,95% CI 1.08-1.20; P <0.00001).Conclusion Compared with pioglitazone,rosiglitazone was associated with an increased risk of myocardial infarction,heart failure,and all-cause mortality in diabetic patients.

  13. Pioglitazone upregulates angiotensin converting enzyme 2 expression in insulin-sensitive tissues in rats with high-fat diet-induced nonalcoholic steatohepatitis.

    Science.gov (United States)

    Zhang, Wei; Xu, Yi-Zhi; Liu, Bo; Wu, Rong; Yang, Ying-Ying; Xiao, Xiao-Qiu; Zhang, Xia

    2014-01-01

    Thiazolidinediones (TZDs) can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH). Angiotensin (Ang) II, the primary effector of renin-angiotensin system (RAS), plays vital roles in the development and progression of NASH. And some AngII-mediated effects can be regulated by TZDs. Angiotensin-converting enzyme (ACE) 2, a new component of RAS, can degrade Ang II to attenuate its subsequent physiological actions. We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats. Forty rats were divided into the normal control, high-fat diet (HFD), pioglitazone control, and HFD plus pioglitazone groups. After 24 weeks of treatment, we evaluated changes in liver histology and tissue-specific ACE2 expression. ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group. Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues.

  14. Genotype Phenotype Correlation of Genetic Polymorphism of PPAR Gamma Gene and Therapeutic Response to Pioglitazone in Type 2 Diabetes Mellitus- A Pilot Study

    Science.gov (United States)

    Sankaran, Ramalingam; Ramalingam, Sudha; Sairam, Thiagarajan; Somasundaram, LS

    2016-01-01

    Introduction Pro12Ala polymorphism is a missense mutation at codon 12 in peroxisome proliferator-activated receptor γ gene (PPARG). This polymorphism is known to be associated with increased insulin sensitivity. Pioglitazone, a thiazolidinedione, is an anti-diabetic drug which acts as an agonist at PPAR γ receptor. Aim To determine the association between Pro12Ala polymorphism of the PPARG and variation in therapeutic response to the PPARγ agonist, pioglitazone. Materials and Methods The study was done as a hospital based pilot project in 30 patients with type 2 diabetes mellitus, on treatment with sulfonylurea or metformin but without adequate glycaemic control. They were started on pioglitazone as add on therapy for a period of 12 weeks. The participants were categorized as responders and non-responders based on the change in HbA1C level after 12 weeks. Pro12Ala polymorphism was analysed by polymerase chain reaction-restriction fragment length polymorphism. Statistical Analysis Logistic regression analysis was done to evaluate the associations between age, baseline body weight, BMI, waist circumference, waist-hip ratio and Pro12Ala variants with the response to pioglitazone. The p-valuePro12Ala polymorphism and glycaemic response to pioglitazone. PMID:27042481

  15. Controlled clinical study on pancreatic stenting in the relief of pain of advanced pancreatic cancer with dilated pancreatic duct

    Institute of Scientific and Technical Information of China (English)

    高飞

    2014-01-01

    Objective To explore the efficacy of pancreatic stenting in the relief of abdominal pain of advanced pancreatic cancer with dilated pancreatic duct.Methods A tolal of 61 patients with advanced pancreatic carcinoma companied with dilated pancreatic duct were divided into two groups.Twenty-eight cases(two cases were excluded because of stent loss)in stent group treated with

  16. Small Undifferentiated Pancreatic Adenocarcinoma which Mimics IPMN at Imaging

    Directory of Open Access Journals (Sweden)

    Mirko D’Onofrio

    2009-07-01

    Full Text Available Context To present the case of an unusual presentation at imaging of a very small solid undifferentiated pancreatic adenocarcinoma which mimics a side-branch intraductal papillary mucinous neoplasm. Case report The patient came to our hospital for a revaluation of a cystic pancreatic lesion. Ultrasound (US and contrast-enhanced ultrasound (CEUS examinations were carried out. A small cystic lesion of about 1.5 cm in diameter was seen in the posterior aspect of the pancreatic uncinate process A very small, solid, vascularized nodule was detected at CEUS within the lesion. Consequently, the patient underwent CT and MRI. MRI confirmed the presence of an intralesional nodule and communication with the main pancreatic duct was demonstrated, suggesting the diagnosis of intraductal papillary mucinous neoplasm with solid intralesional tissue. A pylorus preserving pancreaticoduodenectomy was carried out. An undifferentiated adenocarcinoma having a notable peripheral inflammatory reaction and dilated branch duct was finally diagnosed. Conclusion To our knowledge, we present for the first time, the case of a very small solid undifferentiated pancreatic adenocarcinoma of the uncinate process which mimicked a side-branch intraductal papillary mucinous neoplasm at imaging. The cystic appearance may be an epiphenomenon of a solid lesion and this possibility has to be considered when one encounters incidental cystic lesions at imaging.

  17. Effects of long-term pioglitazone treatment on peripheral and central markers of aging.

    Directory of Open Access Journals (Sweden)

    Eric M Blalock

    Full Text Available BACKGROUND: Thiazolidinediones (TZDs activate peroxisome proliferator-activated receptor gamma (PPARgamma and are used clinically to help restore peripheral insulin sensitivity in Type 2 diabetes (T2DM. Interestingly, long-term treatment of mouse models of Alzheimer's disease (AD with TZDs also has been shown to reduce several well-established brain biomarkers of AD including inflammation, oxidative stress and Abeta accumulation. While TZD's actions in AD models help to elucidate the mechanisms underlying their potentially beneficial effects in AD patients, little is known about the functional consequences of TZDs in animal models of normal aging. Because aging is a common risk factor for both AD and T2DM, we investigated whether the TZD, pioglitazone could alter brain aging under non-pathological conditions. METHODS AND FINDINGS: We used the F344 rat model of aging, and monitored behavioral, electrophysiological, and molecular variables to assess the effects of pioglitazone (PIO-Actos(R a TZD on several peripheral (blood and liver and central (hippocampal biomarkers of aging. Starting at 3 months or 17 months of age, male rats were treated for 4-5 months with either a control or a PIO-containing diet (final dose approximately 2.3 mg/kg body weight/day. A significant reduction in the Ca(2+-dependent afterhyperpolarization was seen in the aged animals, with no significant change in long-term potentiation maintenance or learning and memory performance. Blood insulin levels were unchanged with age, but significantly reduced by PIO. Finally, a combination of microarray analyses on hippocampal tissue and serum-based multiplex cytokine assays revealed that age-dependent inflammatory increases were not reversed by PIO. CONCLUSIONS: While current research efforts continue to identify the underlying processes responsible for the progressive decline in cognitive function seen during normal aging, available medical treatments are still very limited

  18. Post-partum pancreatitis.

    Directory of Open Access Journals (Sweden)

    Pai P

    1993-04-01

    Full Text Available Acute pancreatitis in pregnancy and post-partum period, rarely encountered in surgical practice, can have a lethal effect on the mother and the foetus. We report here a case of a 35 year old tertigravida who presented with high grade fever, abdominal pain with distension, tachycardia and tachypnoea. Chest examination and X-rays were suggestive of pneumonia. The abdomen was tense and tender. Peristalsis was absent. Ultrasound revealed presence of fluid in the abdominal cavity which on paracentesis was found to contain Gram positive cocci. Fluid amylase levels were high. On exploratory laparotomy, haemorrhagic oedematous pancreatitis was noticed. The patient expired on the 2nd post operative day.

  19. Primary Pancreatic Lymphomas

    Directory of Open Access Journals (Sweden)

    Muhammad Wasif Saif

    2006-05-01

    Full Text Available Extranodal non-Hodgkin’s lymphomas (NHLs represent up to 30-40% of all NHL cases. The gastrointestinal tract is the most commonly involved extranodal site; accounting for about half of such cases [1]. Stomach and the small intestine constitute the most common gastrointestinal sites. Secondary invasion of the pancreas from contiguous, retroperitoneal lymph node disease is the prevalent mode of involvement. Secondary involvement of the pancreas from the duodenum or adjacent peripancreatic lymphadenopathy is well-known. Primary pancreatic lymphoma (PPL is an extremely rare disease [2]. PPL can present as an isolated mass mimicking pancreatic carcinoma. However, unlike carcinomas, PPL are potentially treatable [3].

  20. Chemoradiotherapy in pancreatic carcinoma

    Directory of Open Access Journals (Sweden)

    Pathy Sushmita

    2009-01-01

    Full Text Available Pancreatic cancer patients present late in their course and surgical resection as a modality of treatment is of limited value. Majority develop loco-regional failure and distant metastasis, therefore, adjuvant therapy comprising of radiotherapy and chemotherapy are useful treatment options to achieve higher loco-regional control. Specialized irradiation techniques like intra-operative radiotherapy that help to increase the total tumor dose have been used, however, controvertible survival benefit was observed. Various studies have shown improved median and overall survival with chemoradiotherapy for advanced unresectable pancreatic carcinoma. The role of new agents such as topoisomerase I inhibitors also needs further clinical investigations.

  1. Surgical strategies in the treatment of chronic pancreatitis

    Science.gov (United States)

    Zhao, Xin; Cui, Naiqiang; Wang, Ximo; Cui, Yunfeng

    2017-01-01

    Abstract Background: Chronic pancreatitis (CP) is a common and frequently occurring disease. Pancreaticoduodenectomy (PD), pylorus-preserving pancreaticoduodenectomy (PPPD), and duodenum-preserving pancreatic head resection (DPPHR) are important treatment options for patients with chronic pancreatitis. The Beger and Frey procedures are 2 main duodenum-preserving techniques in duodenum-preserving pancreatic head resection (DPPHR) strategies. We conducted this systematic review and meta-analysis to compare the clinical efficacy of DPPHR versus PD, the Beger procedure versus PD, the Frey procedure versus PD, and the Beger procedure versus the Frey procedure in the treatment of pancreatitis. The optimal surgical option for chronic pancreatitis is still under debate. The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of different surgical strategies for chronic pancreatitis. Methods: Five databases (PubMed, Medline, SinoMed, Embase, and Cochrane Library) were searched with the limitations of human subjects and randomized controlled trials (RCTs) text. Data were extracted by 2 of the coauthors independently and analyzed using the RevMan statistical software, version 5.3. Weighted mean differences (WMDs), risk ratios (RRs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool was used to assess the risk of bias. Results: Seven studies involving a total of 385 patients who underwent the surgical treatments were assessed. The methodological quality of the trials ranged from low to moderate and included PD (n = 134) and DPPHR (n = 251 [Beger procedure = 100; Frey procedure = 109; Beger or Frey procedure = 42]). There were no significant differences between DPPHR and PD in post-operation mortality (RR = 2.89, 95% CI = 0.31–26.87, P = 0.36), pain relief (RR = 1.09, 95% CI = 0.94–1.25, P = 0.26), exocrine insufficiency (follow-up time > 60 months

  2. MR imaging of pancreatic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Katsuyoshi E-mail: itokatsu@po.cc.yamaguchi-u.ac.jp; Koike, Shinji; Matsunaga, Naofumi

    2001-05-01

    This article presents current MR imaging techniques for the pancreas, and review a spectrum of MR imaging features of various pancreatic diseases. These include: 1) congenital anomalies such as anomalous union of pancreatobiliary ducts, divisum, and annular pancreas, 2) inflammatory diseases, including acute or chronic pancreatitis with complications, groove pancreatitis, and autoimmune pancreatitis, tumor-forming pancreatitis, 3) pancreatic neoplasms, including adenocarcinoma, islet cell tumors, and cystic neoplasms (microcystic adenoma, mucinous cystic neoplasms, and intraductal mucin-producing pancreatic tumor). Particular attention is paid to technical advances in MR imaging of the pancreas such as fat-suppression, MR pancreatography (single- or multi-slice HASTE), and thin-section 3D multiphasic contrast-enhanced dynamic sequences. Imaging characteristics that may lead to a specific diagnosis or narrow the differential diagnosis are also discussed.

  3. Pancreatic disorders in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Filippo Antonini; Raffaele Pezzilli; Lucia Angelelli; Giampiero Macarri

    2016-01-01

    An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been rec-orded in patients with inflammatory bowel disease(IBD) compared to the general population.Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced,in some cases pancreatitis were defined as idiopathic,suggesting a direct pancreatic damage in IBD.Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn’s disease and ulcerative colitis.This review will discuss the most common pancreatic diseases seen in patients with IBD.

  4. Pancreatic disorders in inflammatory bowel disease

    Science.gov (United States)

    Antonini, Filippo; Pezzilli, Raffaele; Angelelli, Lucia; Macarri, Giampiero

    2016-01-01

    An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn’s disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD. PMID:27574565

  5. Studies of pancreatic carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    JI Yu-bin; PANG Lin-lin; YU Lei; YANG Hai-fan; LIU Guang-da; LI Hai-jiao

    2008-01-01

    Pancreatic carcinoma is the most common pancreatic neoplasm characterized by latentmorbidit, poor prognosis, high mortality rate and limited choice of treatment. Quite a lot studies focused on its pathogenesis, and showed molecular genetic alterations, which derived of genetic and environmental factors and played an important role in tumorigenesis. Recently, more and more findings laid particular emphasis on the changes of gene molecule and some were confirmed in vitro and in vivo. In this paper, we made a review and summarized the arked molecular changes and signalings of the four pathways to understand their functions in Pancreatic carcinoma. The most important changes concentrate on K-RAS, p16 INK4α, P53 and SMAD4 gene, secondly, the changes of pl4ARF, TGF-β, LKB1 /STK11, BRCA2 and growth factor Hedgehog and Notch path way and Telomere also play a important role in pancreatic carcinoma. The vast majority (83%) of pancreatic carcinomas had a distinctive genetic fingerprint, comprising activation of the K-ras oncogene and inactivation of the p 16 gene, generally also accompanied by alterations in the p53 gene (in 76 % of the tumors). The activation of K-ras appears nearly to be a prerequisite for the development of pancreatic carcinoma. Also, the binary alteration of K-ras and p16 is an extremely uncommon combination among other human tumor types. This particular genetic imprint of pancreatic carcinomas could have diagnostic utility in the evaluation of patients with metastatic adenocarcinoma of unknown primary origin. The evaluation of genetic alterations as they naturally occur in humantumors allows the formulation of hypotheses concerning the biological processes that involve human tumongenesis. A central tenet of tumori genesis, that positive selection is exerted upon those tumor cells that alterrate-limiting regulatory pathways, implies that mutation of one gene abrogates the need for inactivation of another gene in the same tumor suppressive pathway. It

  6. Radical resection of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Alexander Koliopanos; C Avgerinos; Athanasios Farfaras; C Manes; Christos Dervenis

    2008-01-01

    BACKGROUND:Pancreatic adenocarcinoma (PCa) is a disease with dismal prognosis, and the only possibility of cure, albeit small, is based on the combination of complete resection with negative histopathological margins (R0 resection) with adjuvant treatment. Therefore, a lot of effort has been made during the last decade to assess the role of extensive surgery in both local recurrence and survival of patients with PCa. DATA SOURCES:Medline search and manual cross-referencing were utilized to identify published evidence-based data for PCa surgery between 1973 and 2006, with emphasis to feasibility, efifcacy, long-term survival, disease free survival, recurrence rates, pain relief and quality of life. RESULTS: Extended surgery is safe and feasible in high volume surgical centers with comparable short-term results. Organ preserving surgery is a main goal because of quality of life reasons and is performed whenever possible from the tumor extent. Concerning long-term survival major vein resection does not adversely affect outcome. To date, there are no changes in long-term survival attributed to the extended lymph node dissection. However, there is a beneift in locoregional control with fewer local recurrences and extended lymphadenectomy allows better staging for the disease. CONCLUSIONS:Extended PCa surgery is safe and feasible despite the inconclusive results in patient's survival beneift. In the future, appropriately powered randomized trials of standard vs. extended resections may show improved outcomes for PCa patients.

  7. Pharmacokinetics of pioglitazone, a thiazolidinedione derivative, in male Naeini (Iranian fat-tailed) sheep

    DEFF Research Database (Denmark)

    Ghoreishi, Sayed Mehdi; Rajaian, H.; Sheykhzade, Majid

    2012-01-01

    Pioglitazone (PGT) belongs to thiazolidinedione (TZD) family or insulin sensitizers that are potent ligands for peroxisome proliferator activated receptor gamma and are used in the treatment of type 2 diabetes mellitus. It has been shown that injection of TZD in cattle has some useful effects....../kg) was administered to five male sheep. Blood samples were collected at various time intervals, and PGT concentration was measured by a validated high-performance liquid chromatography method. The data obtained were best fitted into a two-compartment model for the IV route, and non-compartmental approach for oral...... route. The bioavailability of PGT was obtained to be approximately 62%. After IV injection of PGT, the elimination half-life (t 1/2ß), the volume of distribution at steady-state (V ss) and the elimination rate constant (k el) were obtained to be 4.04±0.88 h, 0.30±0.06 L/kg and 0.47±0.09 h-1...

  8. Pioglitazone for the treatment of type 2 diabetes in patients inadequately controlled on insulin

    Directory of Open Access Journals (Sweden)

    Stanley S Schwartz

    2010-07-01

    Full Text Available Stanley S SchwartzDiabetes Disease Management at the University of Pennsylvania, Penn Presbyterian Medical Center, Philadelphia Heart Institute, Philadelphia, Pennsylvania, USAAbstract: Insulin resistance and impaired beta-cell function are primary defects that occur early in the course of development of type 2 diabetes. Insulin resistance leads to hyperinsulinemia in order to maintain normal glucose tolerance. In most cases of type 2 diabetes, beta-cell dysfunction develops subsequent to the development of insulin resistance, and it is not until such beta-cell dysfunction develops that any abnormality in glucose tolerance is seen. Insulin resistance is a primary defect in type 2 diabetes. The risk of coronary heart disease is significantly increased in patients with type 2 diabetes. Cardiovascular disease causes 80% of all diabetic mortality, and in 75% of those cases, it is a result of coronary atherosclerosis. These points provide a rationale for early and aggressive management of cardiovascular risk in patients with diabetes. Thiazolidinediones represent an effective tool for targeting some features of this increased risk as they decrease insulin resistance and can prevent and/or delay diabetes progression.Keywords: pioglitazone, type 2 diabetes, insulin

  9. Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Suppresses Rat Prostate Carcinogenesis

    Science.gov (United States)

    Suzuki, Shugo; Mori, Yukiko; Nagano, Aya; Naiki-Ito, Aya; Kato, Hiroyuki; Nagayasu, Yuko; Kobayashi, Mizuho; Kuno, Toshiya; Takahashi, Satoru

    2016-01-01

    Pioglitazone (PGZ), a peroxisome proliferator-activated receptor γ agonist, which is known as a type 2 diabetes drug, inhibits cell proliferation in various cancer cell lines, including prostate carcinomas. This study focused on the effect of PGZ on prostate carcinogenesis using a transgenic rat for an adenocarcinoma of prostate (TRAP) model. Adenocarcinoma lesions as a percentage of overall lesions in the ventral prostate were significantly reduced by PGZ treatment in a dose-dependent manner. The number of adenocarcinomas per given area in the ventral prostate was also significantly reduced by PGZ treatment. The Ki67 labeling index in the ventral prostate was also significantly reduced by PGZ. Decreased cyclin D1 expression in addition to the inactivation of both p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)κB were detected in PGZ-treated TRAP rat groups. In LNCaP, a human androgen-dependent prostate cancer cell line, PGZ also inhibited cyclin D1 expression and the activation of both p38 MAPK and NFκB. The suppression of cultured cell growth was mainly regulated by the NFκB pathway as detected using specific inhibitors in both LNCaP and PC3, a human androgen-independent prostate cancer cell line. These data suggest that PGZ possesses a chemopreventive potential for prostate cancer. PMID:27973395

  10. Laparoscopic pancreatic resection.

    Science.gov (United States)

    Harrell, K N; Kooby, D A

    2015-10-01

    Though initially slow to gain acceptance, the minimally invasive approach to pancreatic resection grew during the last decade and pancreatic operations such as the distal pancreatectomy and pancreatic enucleation are frequently performed laparoscopically. More complex operations such as the pancreaticoduodenectomy may also confer benefits with a minimally invasive approach but are less widely utilized. Though most research to date comparing open and laparoscopic pancreatectomy is retrospective, the current data suggest that compared with open, a laparoscopic procedure may afford postoperative benefits such as less blood loss, shorter hospital stay, and fewer wound complications. Regarding oncologic considerations, despite initial concerns, laparoscopic resection appears to be non-inferior to an open procedure in terms of lymph node retrieval, negative margin rates, and long-term survival. New technologies, such as robotics, are also gaining acceptance. Data show that while the laparoscopic approach incurs higher cost in the operating room, the resulting shorter hospital stay appears to be associated with an equivalent or lower overall cost. The minimally invasive approach to pancreatic resection can be safe and appropriate with significant patient benefits and oncologic non-inferiority based on existing data.

  11. Pancreatic Cancer: A Review.

    Science.gov (United States)

    Yabar, Cinthya S; Winter, Jordan M

    2016-09-01

    Pancreatic cancer is now the third leading cause of cancer related deaths in the United States, yet advances in treatment options have been minimal over the past decade. In this review, we summarize the evaluation and treatments for this disease. We highlight molecular advances that hopefully will soon translate into improved outcomes.

  12. Pancreatitis del surco

    Directory of Open Access Journals (Sweden)

    Susana Araújo-Fernández

    2014-03-01

    It is a rare disease, but we must keep it in mind when we make the differential diagnosis of patients with abdominal pain of unknown origin. It is very important to distinguish this pathology from a pancreatic head carcinoma, as both treatments and prognosis differ greatly, so we believe important communication of a new case.

  13. Autoimmune Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Lien-Fu Lin

    2008-01-01

    Conclusion: AIP should be a differential diagnosis in distal CBD stricture and pancreatic head mass when the patient has: (1 diffuse or long segmental enlargement of the pancreas without peripancreatic fat infiltration, with multiple narrowing of the MPD without much upstream dilatation, or narrowing of the MPD not corresponding to the region of CBD stricture; and (2 abnormal immunoserologic tests.

  14. Hepato-pancreatic ascariasis.

    Science.gov (United States)

    De, Uptal; Mukherjee, M; Das, S; Kumar, Rupesh

    2010-10-01

    Intestinal infestation of humans by Ascaris lumbricoides is endemic in India. The usual habitat of the adult worm is the jejunum. Hepatopancreatic ascariasis (HPA) is designated to a rare group of diseases caused by lodgement of adult worms in the bile or pancreatic ducts. This short report illustrates four rare cases of patients with HPA.

  15. Robot-assisted pancreatoduodenectomy with preservation of the vascular supply for autologous islet cell isolation and transplantation: a case report

    Directory of Open Access Journals (Sweden)

    Giulianotti Piero

    2012-03-01

    Full Text Available Abstract Introduction For patients with chronic pancreatitis presenting with medically intractable abdominal pain, surgical intervention may be the only treatment option. However, extensive pancreatic resections are typically performed open and are associated with a substantial amount of postoperative pain, wound complications and long recovery time. Minimally invasive surgery offers an avenue to improve results; however, current limitations of laparoscopic surgery render its application in the setting of chronic pancreatitis technically demanding. Additionally, pancreatic resections are associated with a high incidence of diabetes. Transplantation of islets isolated from the resected pancreas portion offers a way to prevent post-surgical diabetes; however, preservation of the vascular supply during pancreatic resection, which determines islet cell viability, is technically difficult using current laparoscopic approaches. With recent advances in the surgical field, robotic surgery now provides a means to overcome these obstacles to achieve the end goals of pain relief and preserved endocrine function. We present the first report of a novel, minimally invasive robotic approach for resection of the pancreatic head that preserves vascular supply and enables the isolation of a high yield of viable islets for transplantation. Case presentation A 35-year old Caucasian woman presented with intractable chronic abdominal pain secondary to chronic pancreatitis, with a stricture of her main pancreatic duct at the level of the ampulla of Vater and distal dilatation. She was offered a robotic-assisted pylorus-preserving pancreatoduodenectomy and subsequent islet transplantation, to both provide pain relief and preserve insulin-secretory reserves. Conclusion We present a novel, minimally invasive robotic approach for resection of the pancreatic head with complete preservation of the vascular supply, minimal warm ischemia time (less than three minutes and

  16. Study on chronic pancreatitis and pancreatic cancer using MRS and pancreatic juice samples

    Institute of Scientific and Technical Information of China (English)

    Jian Wang; Chao Ma; Zhuan Liao; Bing Tian; Jian-Ping Lu

    2011-01-01

    AIM: To investigate the markers of pancreatic diseases and provide basic data and experimental methods for the diagnosis of pancreatic diseases. METHODS: There were 15 patients in the present study, among whom 10 had pancreatic cancer and 5, chronic pancreatitis. In all patients, pancreatic cancer or chronic pancreatitis was located on the head of the p-a-ncreas. Pathology data of all pa tients was confirmed by biopsy and surgery. Among the 10 patients with pancreatic cancer, 3 people had a medical history of longterm alcohol consumption. Of 5 patients with chronic pancreatitis, 4 men suffered from alcoholic chronic pancreatitis. Pancreatic juice samples were obtained from patients by endoscopic retrograde cholangiopancreatography. Magnetic resonance spectroscopyn was performed on an 11.7-T scanner (Bruker DRX-500) using Call-Purcell-Meiboom-Gill pulse sequences. The parameters were as follows: spectral width, 15 KHz; time domain, 64 K; number of scans, 512; and acquisition time, 2.128 s. RESULTS: The main component of pancreatic juice included leucine, iso-leucine, valine, lactate, alanine, acetate, aspartate, lysine, glycine, threonine, tyrosine, histidine, tryptophan, and phenylalanine. On performing 1D 1H and 2D total correlation spectroscopy, we found a triplet peak at the chemical shift of 1.19 ppm, which only appeared in the spectra of pancreatic juice obtained from patients with alcoholic chronic pancreatitis. This triplet peak was considered the resonance of the methyl of ethoxy group, which may be associated with the metabolism of alcohol in the pancreas. CONCLUSION: The triplet peak, at the chemical shift of 1.19 ppm is likely to be the characteristic metabolite of alcoholic chronic pancreatitis.

  17. Regulation of insulin degrading enzyme activity by obesity-associated factors and pioglitazone in liver of diet-induced obese mice.

    Directory of Open Access Journals (Sweden)

    Xiuqing Wei

    Full Text Available Insulin degrading enzyme (IDE is a potential drug target in the treatment of type 2 diabetes (T2D. IDE controls circulating insulin through a degradation-dependent clearance mechanism in multiple tissues. However, there is not sufficient information about IDE regulation in obesity. In this study, we test obesity-associated factors and pioglitazone in the regulation of IDE in diet-induced obese (DIO C57BL/6 mice. The enzyme activity and protein level of IDE were increased in the liver of DIO mice. Pioglitazone (10 mg/kg/day administration for 2 months significantly enhanced the enzyme activity (75%, protein (180% and mRNA (100% of IDE in DIO mice. The pioglitazone-induced changes were coupled with 50% reduction in fasting insulin and 20% reduction in fasting blood glucose. The mechanism of IDE regulation in liver was investigated in the mouse hepatoma cell line (Hepa 1c1c7 cells, in which pioglitazone (5 µM increased IDE protein and mRNA in a time-dependent manner in an 8 h study. Free fatty acid (palmitate 300 µM induced IDE protein, but reduced the mRNA. Glucagon induced, and TNF-α decreased IDE protein. Insulin did not exhibit any activity in the same condition. In summary, pioglitazone, FFA and glucagon directly increased, but TNF-α decreased the IDE activity in hepatocytes. The results suggest that IDE activity is regulated in liver by multiple factors in obesity and pioglitazone may induce IDE activity in the control of T2D.

  18. Effect of pioglitazone versus insulin glargine on cardiac size, function, and measures of fluid retention in patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Groop Leif

    2009-03-01

    Full Text Available Abstract Background Both insulin and thiazolidinediones (TZDs are effective in the treatment of hyperglycaemia and amelioration of insulin resistance in type 2 diabetes but have side effects including weight gain and fluid retention. The use of TZDs has been further hampered by the risk of adverse cardiovascular events including heart failure. The present study evaluated the effect of pioglitazone or insulin glargine on cardiac function and size as well as on surrogate markers of fluid retention such as weight, haemoglobin and natriuretic peptides. Methods Thirty patients with inadequate glycaemic control on metformin and sulfonylurea were randomised to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Echocardiographic data and blood samples were collected from the two groups before the start of the treatment and after 26 weeks. Left ventricular end-diastolic and left atrial end-systolic volumes were quantified, weight measured and blood samples analyzed. Results After 26 weeks of treatment, the changes in HbA1c, weight and haemoglobin were similar between the two groups. HDL increased significantly in the pioglitazone group. While there was an increase in natriuretic peptides in the pioglitazone group (NT-proBNP 11.4 ± 19.6 to 22.8 ± 44.0, p = 0.046, the difference between the treatment groups was not significant. Left ventricular end-diastolic volume increased by 11% and left atrial end-systolic volume by 17% in the pioglitazone group (Both, p Conclusion This randomised pilot-study showed that six-month treatment with pioglitazone induced significant increases in natriuretic peptides and alterations of cardiac size. These changes were not observed with insulin glargine, which also is known to induce fluid retention. Larger randomised trials are warranted to confirm these findings.

  19. Pioglitazone-induced increase in the stearoyl-CoA desaturation index and fat accumulation in rat muscles are not related to lipoprotein lipase activity.

    Science.gov (United States)

    Ochiai, Masaru; Matsuo, Tatsuhiro

    2013-01-01

    Muscular insulin resistance is a characteristic of obesity and type 2 diabetes, but little is known about fatty acid (FA) metabolism in insulin-resistant skeletal muscle. In this study, we investigated the effects of the repeated administration of the PPAR-γ agonist pioglitazone on fat accumulation, FA composition, and stearoyl-CoA desaturase (SCD) index in rat tissues. Seventeen 4-week-old male Wistar rats were divided into control (C, n = 9) and pioglitazone treatment (P, n = 8) groups, and all the rats were fed a high-fat and high-sucrose diet for 8 weeks. Vehicle or pioglitazone (3 mg/kg) was orally administered daily to rats in the C group and P group, respectively. In the eighth week of the test period, an oral glucose tolerance test (OGTT) was performed after 12 h fasting. At the end of the test period, serum, liver, perirenal adipose tissue, and skeletal muscles were removed after 12 h fasting. The fasting serum and plasma glucose concentrations and OGTT glucose and insulin levels were significantly lower, while the serum adiponectin concentration was significantly higher in the P group than in the C group. Pioglitazone administration increased fat accumulation in the various muscle types examined, perirenal adipose tissue, and brown adipose tissue (BAT), but decreased fat accumulation in the liver. Pioglitazone administration increased the SCD indices for the muscles, perirenal adipose tissue, and liver, but not those of BAT. The lipoprotein lipase (LPL) activity of the BAT and perirenal adipose tissue, but not the muscles, was higher in the P group than in the C group. These results indicate that pioglitazone administration improved glucose tolerance and increased fat accumulation and SCD indices in the muscles and adipose tissues of rats. The increased fat accumulation was closely correlated with LPL activity in both adipose tissues, but not in the muscles.

  20. Acute pancreatitis: Etiology and common pathogenesis

    Institute of Scientific and Technical Information of China (English)

    Guo-Jun Wang; Chun-Fang Gao; Dong Wei; Cun Wang; Si-Qin Ding

    2009-01-01

    Acute pancreatitis is an inflammatory disease of the pancreas. The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide. Many causes of acute pancreatitis have been discovered, but the pathogenetic theories are controversial. The most common cause of acute pancreatitis is gallstone impacting the distal common bile-pancreatic duct. The majority of investigators accept that the main factors for acute billiary pancreatitis are pancreatic hyperstimulation and bile-pancreatic duct obstruction which increase pancreatic duct pressure and active trypsin reflux. Acute pancreatitis occurs when intracellular protective mechanisms to prevent trypsinogen activation or reduce trypsin activity are overwhelmed. However, little is known about the other acute pancreatitis. We hypothesize that acute biliary pancreatitis and other causes of acute pancreatitis possess a common pathogenesis. Pancreatic hyperstimulation and pancreatic duct obstruction increase pancreatic duct pressure, active trypsin reflux, and subsequent unregulated activation of trypsin within pancreatic acinar cells. Enzyme activation within the pancreas leads to auto-digestion of the gland and local inflammation. Once the hypothesis is confirmed, traditional therapeutic strategies against acute pancreatitis may be improved. Decompression of pancreatic duct pressure should be advocated in the treatment of acute pancreatitits which may greatly improve its outcome.

  1. A cost-effectiveness analysis of pioglitazone plus metformin compared with rosiglitazone plus metformin from a third-party payer perspective in the US.

    Science.gov (United States)

    St Charles, Meaghan; Minshall, Michael E; Pandya, Bhavik J; Baran, Robert W; Tunis, Sandra L

    2009-06-01

    The long-term cost-effectiveness of using pioglitazone plus metformin (Actoplusmet dagger) compared with rosiglitazone plus metformin (Avandamet double dagger) in treating type 2 diabetes (T2DM) was assessed from a US third-party payer perspective. Clinical efficacy (change in HbA(1c) and lipids) and baseline cohort parameters were extracted from a 12-month, randomized clinical trial (Derosa et al., 2006) evaluating the efficacy and tolerability of pioglitazone versus rosiglitazone, both in addition to metformin, in adult T2DM patients with insufficient glucose control (n = 96). A Markov-based model was used to project clinical and economic outcomes over 35 years, discounted at 3% per annum. Costs for complications were taken from published sources. Base-case assumptions were assessed through several sensitivity analyses. Outcomes included incremental life-years, quality-adjusted life-years (QALYs), total direct medical costs, cumulative incidence of complications and associated costs, and incremental cost-effectiveness ratios (ICERs). Compared to rosiglitazone plus metformin, pioglitazone plus metformin was projected to result in a modest improvement in 0.187 quality-adjusted life-years. Over patients' lifetimes, total direct medical costs were projected to be marginally lower with pioglitazone plus metformin (difference -$526.), largely due to reduced CVD complication costs. While costs were higher among renal, ulcer/amputation/neuropathy, and eye complications in the pioglitazone plus metformin group, the cost savings for CVD complications outweighed their economic impact. Pioglitazone plus metformin was found to be a dominant long-term treatment strategy in the US compared to rosiglitazone plus metformin. Sensitivity analyses showed findings to be robust under almost all scenarios, including short-term time horizons, 6% discounting, removal of individual lipid parameters, and modifications of patient cohort to more closely represent a US T2DM population

  2. Pioglitazone inhibition of lipopolysaccharide-induced nitric oxide synthase is associated with altered activity of p38 MAP kinase and PI3K/Akt

    Directory of Open Access Journals (Sweden)

    Hunter Randy

    2008-01-01

    Full Text Available Abstract Background Previous studies have suggested that peroxisome proliferator activated receptor-gamma (PPAR-γ-mediated neuroprotection involves inhibition of microglial activation and decreased expression and activity of inducible nitric oxide synthase (iNOS; however, the underlying molecular mechanisms have not yet been well established. In the present study we explored: (1 the effect of the PPAR-γ agonist pioglitazone on lipopolysaccharide (LPS-induced iNOS activity and nitric oxide (NO generation by microglia; (2 the differential role of p38 mitogen-activated protein kinase (p38 MAPK, c-Jun NH(2-terminal kinase (JNK, and phosphoinositide 3-kinase (PI3K on LPS-induced NO generation; and (3 the regulation of p38 MAPK, JNK, and PI3K by pioglitazone. Methods Mesencephalic neuron-microglia mixed cultures, and microglia-enriched cultures were treated with pioglitazone and/or LPS. The protein levels of iNOS, p38 MAPK, JNK, PPAR-γ, PI3K, and protein kinase B (Akt were measured by western blot. Different specific inhibitors of iNOS, p38MAPK, JNK, PI3K, and Akt were used in our experiment, and NO generation was measured using a nitrite oxide assay kit. Tyrosine hydroxylase (TH-positive neurons were counted in mesencephalic neuron-microglia mixed cultures. Results Our results showed that pioglitazone inhibits LPS-induced iNOS expression and NO generation, and inhibition of iNOS is sufficient to protect dopaminergic neurons against LPS insult. In addition, inhibition of p38 MAPK, but not JNK, prevented LPS-induced NO generation. Further, and of interest, pioglitazone inhibited LPS-induced phosphorylation of p38 MAPK. Wortmannin, a specific PI3K inhibitor, enhanced p38 MAPK phosphorylation upon LPS stimulation of microglia. Elevations of phosphorylated PPAR-γ, PI3K, and Akt levels were observed with pioglitazone treatment, and inhibition of PI3K activity enhanced LPS-induced NO production. Furthermore, wortmannin prevented the inhibitory effect of

  3. Analysis of Case Reports of Pioglitazone's Adverse Drug Reaction%吡格列酮的不良反应病例报告分析

    Institute of Scientific and Technical Information of China (English)

    曾艳; 李晓玲; 王育琴

    2011-01-01

    Objective:To review and analyze the case reports of pioglitazone' s adverse drug reactions to provide reference for rational and safe use of pioglitazone. Method: Reactions Weekly was searched for case reports with the key word ' pioglitazone' , types of ADRs of the case reports were classified and the patients' clinical characteristics, types and outcome of ADRs were analyzed. Result:41 case reports of ADRs associated with pioglitazone were found. 41 patients consisted of 21 males, 19 females and 1 unidentified, and were aged 30 -82 years with a pioglitazone' s dosage 15 -45 mg per day and its duration from 1 week to 2 years. Their ADRs were involved in many systems such as cardiovascular system, respiratory system and biliary system. Except for 1 patient with unaquired outcome, 8 patients died, the rest recovered after pioglitazone' s discontinuation with or without therapy. Conclusion: Pioglitazone could induce severe adverse reactions such as heart failure and liver failure. The medical staff should monitor ADR as they used piolitazone.%目的:对吡格列酮药品不良反应(ADR)病例报告进行回顾分析,为临床合理安全使用提供参考.方法:以"pioglitazone"为检索词检索Reactions Weekly,将检索到的ADR病例报告分类,分别提取患者的临床特征及ADR类型、转归等信息,进行统计分析.结果:检索到与吡格列酮相关ADR病例报告41份.41名患者中男21例,女19例,1名性别不明.年龄30-82岁,吡格列酮剂量15-45 mg·d-1,疗程1周-2年.发生ADR分别涉及心血管系统、呼吸系统、肝胆系统等多个系统/器官.41名患者中1名转归不明,8名死亡,其余患者停药后或停药经治疗后好转或痊愈.结论:吡格列酮引起的心衰、肝衰竭等ADR会给患者带来较大危害,甚至危及到生命.医务人员在使用吡格列酮的同时,要关注其ADR.

  4. Acute pancreatitis: clinical vs. CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Hill, M.C. (Univ. of Miami, FL); Barkin, J.; Isikoff, M.B.; Silver stein, W.; Kalser, M.

    1982-08-01

    In a prospective study of 91 patients with acute pancreatitis, computed tomographic (CT) findings were correlated with the clinical type of acute pancreatitis. In acute edematous pancreatitis (63 patients; 16 with repeat CT), CT was normal (28%) or showed inflammation limited to the pancreas (61%). Phlegmonous changes were present in 11%, including one patient with focal pancreatic hemorrhage, indicating that clinically unsuspected hemorrhagic pancreatitis can occur. In acute necrotizing (hemorrhagic, suppurative) pancreatitis (nine patients; eight with repeat CT), no patient had a normal CT scan and 89% had phlegmonous changes. One patient had hemorrhagic pancreatitis and three had abscesses. In acute exacerbation of chronic pancreatitis (10 patients; three with repeat CT), there were pancreatic calcifications (70%), a focal mass (40%), and pancreatic ductal dilation (30%). On follow-up CT, the findings of acute pancreatitis did not always disappear with resolution of the clinical symptons. This was especialy true of phlegmonous pancreatitis, where the CT findings could persist for months.

  5. Acute Pancreatitis: Surgery, Pathophysiology and Probiotic Prophylaxis

    NARCIS (Netherlands)

    Minnen, L.P. van

    2006-01-01

    Acute pancreatitis is a challenging disease with a clinical course that is often difficult to predict. In severe acute pancreatitis, mortality increases significantly if intestinal bacteria translocate from the intestine and infect pancreatic necrosis. Surgical and prophylactic treatment strategies

  6. Asparaginase-associated pancreatitis in children

    DEFF Research Database (Denmark)

    Raja, Raheel Altaf; Schmiegelow, Kjeld; Frandsen, Thomas Leth

    2012-01-01

    , allergic reactions, thrombotic events, hepatotoxicity and hyperlipidaemia. Acute pancreatitis is one of the most common reasons for stopping treatment with l-asparaginase. Short-term complications of asparaginase-associated pancreatitis include development of pseudocysts and pancreatic necrosis. Long...

  7. Patient Derived Cancer Cell Lines in Identifying Molecular Changes in Patients With Previously Untreated Pancreatic Cancer Receiving Gemcitabine Hydrochloride-Based Chemotherapy

    Science.gov (United States)

    2016-10-18

    Pancreatic Ductal Adenocarcinoma; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  8. Possible Involvement of Pancreatic Fatty Infiltration in Pancreatic Carcinogenesis

    OpenAIRE

    Mika Hori; Michihiro Mutoh; Toshio Imai; Hitoshi Nakagama; Mami Takahashi

    2016-01-01

    Pancreatic cancer is difficult to diagnose in its early stage and is one of the most lethal human cancers. Thus, it is important to clarify its major risk factors, predictive factors and etiology. Here, we focus on fatty infiltration of the pancreas and suggest that it could be a risk factor for pancreatic cancer. Fatty infiltration of the pancreas is observed as ectopic adipocytes infiltrating the pancreatic tissue and is positively correlated with obesity and the prevalence of diabetes mell...

  9. [Preservatives in ophthalmology].

    Science.gov (United States)

    Messmer, E M

    2012-11-01

    Preservatives are a legal requirement for eye drops in multidose containers. Moreover, they are necessary for stabilization and intraocular penetration for a number of ophthalmic preparations. Most preservatives act in a relatively unspecific manner as detergents or by oxidative mechanisms and thereby cause side effects at the ocular surface. They may also affect the lens, trabecular meshwork and the retina. Benzalkonium chloride is the most commonly used preservative in ophthalmology and is more toxic than other or newer preservatives, such as polyquaternium-1 (Polyquad), sodium perborate, oxychloro-complex (Purite®) and SofZia. Preservative-free topical medication is highly recommended for patients with ocular surface disease, frequent eye drop administration, proven allergy to preservatives and contact lens wear.

  10. Pioglitazone ameliorates nonalcoholic steatohepatitis by down-regulating hepatic nuclear factor-kappa B and cyclooxygenases-2 expression in rats

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jia-sheng; ZHU Feng-shang; LIU Su; YANG Chang-qing; CHEN Xi-mei

    2012-01-01

    Background Pioglitazone is effective in nonalcoholic steatohepatitis (NASH),but the mechanisms of action are not completely understood.This study was designed to investigate the effects of pioglitazone on hepatic nuclear factor-kappa B (NF-κB) and cyclooxygenases-2 (COX-2) expression in NASH rats.Methods Thirty Sprague-Dawley male rats were randomly assigned to a control group (n=10),NASH group (n=10),and pioglitazone treatment group (n=10).Liver tissues were processed for histology by hematoxylin & eosin and Masson stained.Serum alanine aminotransferase (ALT),cholesterol,triglyceride,fasting blood glucose (FBG),fasting insulin (FINS) levels and biochemical parameters of antioxidant enzyme activities,tumor necrosis factor alpha (TNF-α),prostaglandin E2 (PGE2) levels in serum and liver were measured.The mRNA and protein expression of peroxisome proliferator-activated receptor gamma (PPARy),NF-κB and COX-2 were determined by real-time polymerase chain reaction,Westem blotting and immunohistochemistry.One-way analysis of variance (ANOVA) and Wilcoxon's signed-rank test was used for the statistical analysis.Results There were severe steatosis,moderate inflammatory cellular infiltration and fibrosis in NASH rats.After pioglitazone treatment,steatosis,inflammation and fibrosis were significantly improved compared with the NASH group(X2=20.40,P <0.001; )X2=20.17,P <0.001; X2=13.98,P=0.002).Serum ALT,cholesterol,triglyceride,FBG,FINS levelswere significantly elevated in the NASH group (P <0.05).In the NASH group,total anti-oxidation competence (T-AOC),superoxide dismutase (SOD),catalase (CAT),glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) levels inserum and liver were conspicuous disordered than those parameters in the control group.Meanwhile,TNF-α and PGE2levels in serum and liver were significantly increased compared with the control group.Immunohistochemistry showedNF-KB and COX-2 expression in liver was significantly elevated.However,PPARy level

  11. Pancreatic resections for solid or cystic pancreatic masses in children.

    Science.gov (United States)

    Muller, C O; Guérin, F; Goldzmidt, D; Fouquet, V; Franchi-Abella, S; Fabre, M; Branchereau, S; Martelli, H; Gauthier, F

    2012-03-01

    The aim of the study was to assess the diagnosis and management of solid pancreatic neoplasm in children and the type of surgical treatment, focusing on short- and long-term outcomes. We retrospectively reviewed the charts of all children who had undergone pancreatic resection for suspicion of pancreatic tumor in Kremlin Bicêtre Hospital, Paris, between 1986 and 2008. We studied the symptoms at diagnosis, the type of surgery, and the short- and long-term morbidity and mortality. Of 18 patients identified, there were 7 pseudopapillary tumors, 3 neuroblastomas, 2 rhabdomyosarcomas, 1 acinar cell carcinoma, 1 endocrine cell carcinoma, 1 renal angiomyolipoma, and 3 pancreatic cysts. Symptoms at diagnosis were abdominal trauma, abdominal mass, and jaundice. Operative procedures were duodenopancreatectomy (11), mid-pancreatic resections (2), splenopancreatectomy (2), distal pancreatectomy (1), and tumorectomy (2). There were no deaths related to surgery. The postoperative morbidity rate was 45%, including 2 cases of fistula (11%) occurring after a mid-pancreatic resection and a pancreaticoduodenectomy. The median follow-up was 4.2 years (range 2-11). There was no diabetes mellitus, but there was 1 case of fat diet intolerance requiring pancreatic enzyme substitution. All of the children had a growth curve within normal limits. In this experience, pancreatic resections have proven to be a safe and efficient procedure, with low long-term morbidity, for the treatment of tumoral and selected nontumoral pancreatic masses.

  12. Molecular mechanisms of pancreatic stone formation in chronic pancreatitis.

    Directory of Open Access Journals (Sweden)

    Shigeru B.H. Ko

    2012-11-01

    Full Text Available Chronic pancreatitis (CP is a progressive inflammatory disease in which the pancreatic secretory parenchyma is destroyed and replaced by fibrosis. The presence of intraductal pancreatic stone(s is important for the diagnosis of CP; however, the precise molecular mechanisms of pancreatic stone formation in CP were left largely unknown. CFTR is a chloride channel expressed in the apical plasma membrane of pancreatic duct cells and plays a central role in HCO3- secretion. In previous studies, we have found that CFTR is largely mislocalized to the cytoplasm of pancreatic duct cells in all forms of CP and corticosteroids normalizes the localization of CFTR to the proper apical membrane at least in autoimmune pancreatitis. From these observations, we could conclude that the mislocalization of CFTR is a cause of protein plug formation in CP, subsequently resulting in pancreatic stone formation.Considering our observation that the mislocalization of CFTR also occurs in alcoholic or idiopathic CP, it is very likely that these pathological conditions can also be treated by corticosteroids, thereby preventing pancreatic stone formation in these patients. Further studies are definitely required to clarify these fundamental issues.

  13. Preserving Digital Materials

    CERN Document Server

    Harvey, Ross

    2011-01-01

    This book provides a single-volume introduction to the principles, strategies and practices currently applied by librarians and recordkeeping professionals to the critical issue of preservation of digital information. It incorporates practice from both the recordkeeping and the library communities, taking stock of current knowledge about digital preservation and describing recent and current research, to provide a framework for reflecting on the issues that digital preservation raises in professional practice.

  14. Role of bacterial infections in pancreatic cancer

    OpenAIRE

    Michaud, Dominique S.

    2013-01-01

    Established risk factors for pancreatic cancer, including tobacco smoking, chronic pancreatitis, obesity and type 2 diabetes, collectively account for less than half of all pancreatic cancer cases. Inflammation plays a key role in pancreatic carcinogenesis, but it is unclear what causes local inflammation, other than pancreatitis. Epidemiological data suggest that Helicobacter pylori may be a risk factor for pancreatic cancer, and more recently, data suggest that periodontal disease, and Porp...

  15. Genetically Determined Chronic Pancreatitis but not Alcoholic Pancreatitis Is a Strong Risk Factor for Pancreatic Cancer.

    Science.gov (United States)

    Midha, Shallu; Sreenivas, Vishnubhatla; Kabra, Madhulika; Chattopadhyay, Tushar Kanti; Joshi, Yogendra Kumar; Garg, Pramod Kumar

    2016-11-01

    To study if chronic pancreatitis (CP) is a risk factor for pancreatic cancer. Through a cohort and a case-control study design, CP and other important risk factors including smoking, diabetes, alcohol, obesity, and genetic mutations were studied for their association with pancreatic cancer. In the cohort study, 402 patients with CP were included. During 3967.74 person-years of exposure, 5 of the 402 patients (4 idiopathic CP, 1 hereditary CP) developed pancreatic cancer after 16.60 ± 3.51 years of CP. The standardized incidence ratio was 121. In the case-control study, 249 pancreatic cancer patients and 1000 healthy controls were included. Of the 249 patients with pancreatic cancer, 24 had underlying idiopathic CP, and none had alcoholic pancreatitis. SPINK1 gene mutation was present in 16 of 26 patients with idiopathic CP who had pancreatic cancer. Multivariable analysis showed CP (odds ratio [OR], 97.67; 95% confidence interval [CI], 12.69-751.36), diabetes (>4 years duration) (OR, 3.05; 95% CI, 1.79-5.18), smoking (OR, 1.93; 95% CI, 1.38-2.69) as significant risk factors for pancreatic cancer. The population attributable risk was 9.41, 9.06, and 9.50 for diabetes, CP, and smoking, respectively. Genetically determined CP but not alcoholic CP is a strong risk factor for pancreatic cancer.

  16. Carbofuran-Induced Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Rizos E

    2004-01-01

    Full Text Available CONTEXT: Carbamate insecticides are widely used in commercial agriculture and home gardening. A serious side effect of organophosphate and carbamate intoxication is the development of acute pancreatitis. CASE REPORT: A 36-year-old Caucasian woman was admitted to our hospital with cholinergic crisis and pancreatitis soon after the ingestion of a carbamate insecticide (carbofuran. An abdominal CT scan disclosed pancreatic necrosis with intrapancreatic fluid collection, consistent with the development of a pancreatic pseudocyst in a subsequent CT scan. No predisposing factor for pancreatitis was evident. Pseudocholinesterase levels returned to normal 7 days later and the patient was discharged in good physical condition one month after admission. DISCUSSION: Although acute pancreatitis is not infrequent after organophosphate intoxication, it is quite rare after carbamate ingestion and has not been previously reported after carbofuran intoxication.

  17. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone

    OpenAIRE

    Forst, T; Guthrie, R.; Goldenberg, R; Yee, J.; Vijapurkar, U; Meininger, G; Stein, P.

    2014-01-01

    Aim The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and pioglitazone. Methods In this randomized, double-blind, phase 3 study, patients (N = 342) received canagliflozin 100 or 300 mg during a 26-week, placebo-controlled, core period and a 26-week, active-controlled extension in which placebo-treated patients were switched to sitagliptin 100 mg. Efficacy ...

  18. CT findings of pancreatic disease

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mi Sook; Park, In Sook; Jeon, Doo Sung; Kim, Hong Soo; Rhee, Hak Song [Presbyterian Medical Center, Jeonju (Korea, Republic of); Won, Jong Jin [College of Medicine, Wonkwang University, Iri (Korea, Republic of)

    1988-02-15

    CT was found to be a reliable, often specific, and noninvasive method for detecting pancreatic diseases. In a study of pancreatic lesions, 37 cases having satisfactory operative and histological proofs were analyzed by CT at PMC from Jan. 1986 to Oct. 1987. The results were as following: 1. Male:female is 26:11. 2. The incidence of pancreatic disease were as follows: 1) Pancreatic cancer:21 cases (56%) a.Head:12 cases b.Body:4 cases c.Tail:1 case d.Body and tail:1 case e.Uncinate process:2 cases f.Entire pancreas: 1 case 2) Acute pancreatitis: 6 cases (16%) 3) Chronic pancreatitis:5 cases (14%) 3. The characteristic CT findings: 1) 100% of pancreatic head cancer showed focal mass or alteration of pancreatic head contour and biliary tree dilatation, and 33% (7/12) fat line obliteration. 2) All of other pancreatic cancer except head appeared as focal mass or contour alteration and fat line obliteration. 3) Total 6 cases of acute pancreatitis showed that 5 cases diffuse enlargement of pancreas, 3 fluid collection (2 cases:left anterior pararenal and posterior pararenal space and lesser sac, 1 case:only pancreas body) and 1 case abscess formation. 4) Total 5 cases of chronic pancreatitis revealed diffuse enlargement 2 cases and atrophy 1 case, pancreatic ductal dilatation 3 cases, calcification 2 cases, and biliary tree dilatation with CBD tapering appearance 1 case. 5) All cases of pseudocysts were well marginated cystic lesions that located at head in 3 cases and tail 3 cases, and 4 cases were well defined pure cystic masses but 1 case was well capsulated cyst with multiple internal septation.

  19. The role of pancreaticoduodenectomy in the treatment of severe chronic pancreatitis.

    Science.gov (United States)

    Vickers, S M; Chan, C; Heslin, M J; Bartolucci, A; Aldrete, J S

    1999-12-01

    Chronic pancreatitis remains a debilitating disease with few definitive options for treatment. The purpose of this study was to evaluate the benefit of pancreaticoduodenectomy in the treatment of chronic pancreatitis. The results were evaluated by standard descriptive statistics. In a retrospective study, we reviewed the patients at a single institution undergoing pancreaticoduodenectomy between 1994 and 1997 for complications of chronic pancreatitis. Patients were evaluated for preoperative indication for surgery and perioperative morbidity and mortality, as well as long-term results. Thirty-two patients underwent pancreaticoduodenectomy for chronic pancreatitis; 56 per cent (18) underwent pylorus-preserving and 44 per cent (14) underwent classic pancreaticoduodenectomy. The mean age of these patients was 56+/-14.7 years (range, 23-79). All patients underwent preoperative CT scan and endoscopic retrograde cholangiopancreatography. The preoperative indication for surgery in 81 per cent (26) of these patients was intractable pain in the setting of a nondilated pancreatic duct. The other 19 per cent were treated for biliary/pancreatic duct stricture and pancreatic head fibrosis (mass suspicious of malignancy). Fifty-three per cent of the patients had a history of previous abdominal surgery. There were no perioperative deaths. The mean postoperative stay was 12.2+/-7.4 days. The postoperative morbidity rate was 31 per cent (10), consisting of 25 per cent with delayed gastric emptying, 3 per cent with pneumonia, and 3 per cent with wound infections. There was no occurrence of pancreatic fistulas. With a mean follow-up of 40 months (range, 10-52 months), 85 per cent reported a significant improvement in pain with 71 per cent being pain free and not requiring narcotics. Twenty per cent developed new-onset diabetes. The overall event survival rate at 5 years was 97 per cent. Thus, in a selected group of patients with severe chronic pancreatitis, resection of the head of

  20. Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1

    Directory of Open Access Journals (Sweden)

    Marcel Cerqueira Cesar Machado

    Full Text Available Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and

  1. Rapid Evolution from the First Episode of Acute Pancreatitis to Chronic Pancreatitis in Human Subjects

    OpenAIRE

    Elie Aoun; Adam Slivka; Papachristou, Dionysios J.; Whitcomb, David C.; Gleeson, Ferga C; Papachristou, Georgios I

    2007-01-01

    Context Growing evidence suggests that recurrent acute pancreatitis leads to chronic pancreatitis, but this sequence is seldom reported in human subjects. The sentinel acute pancreatitis event hypothesis suggests that an initial episode of acute pancreatitis is the first step in a complicated series of events ultimately leading to chronic pancreatitis. Objective To identify patients who evolved from recurrent acute pancreatitis to chronic pancreatitis. Setting The Severity of Acute Pancreatit...

  2. Acute Pancreatitis Associated with Brucellosis

    Directory of Open Access Journals (Sweden)

    Demetrios Papaioannides

    2006-01-01

    Full Text Available Context :Acute pancreatitis can be caused by a variety of infectious agents but it is regarded as an extremely rare complication of brucellosis. Case report: We briefly describe a 56-yearold man who presented with acute pancreatitis, fever, myalgia, and other clinical symptoms. Brucella melitensis was cultured from his blood. All clinical manifestations gradually resolved with the institution of intramuscular streptomycin and oral doxycycline therapy. Conclusion :Acute pancreatitis may rarely be a complication of infection with B. melitensis. In areas where brucellosis is endemic, it should be kept in mind that acute pancreatitis may result from infection with brucella organisms..

  3. Early management of acute pancreatitis.

    Science.gov (United States)

    Schepers, Nicolien J; Besselink, Marc G H; van Santvoort, Hjalmar C; Bakker, Olaf J; Bruno, Marco J

    2013-10-01

    Acute pancreatitis is the most common gastro-intestinal indication for acute hospitalization and its incidence continues to rise. In severe pancreatitis, morbidity and mortality remains high and is mainly driven by organ failure and infectious complications. Early management strategies should aim to prevent or treat organ failure and to reduce infectious complications. This review addresses the management of acute pancreatitis in the first hours to days after onset of symptoms, including fluid therapy, nutrition and endoscopic retrograde cholangiography. This review also discusses the recently revised Atlanta classification which provides new uniform terminology, thereby facilitating communication regarding severity and complications of pancreatitis.

  4. An overview of hereditary pancreatitis.

    Science.gov (United States)

    Rebours, Vinciane; Lévy, Philippe; Ruszniewski, Philippe

    2012-01-01

    Hereditary pancreatitis is a rare cause of chronic pancreatitis. The prevalence was evaluated to 0.3/100000 in Western Countries. Genetic disorders are due to mutations of the PRSS1 gene on the long arm of the chromosome 7, encoding for the cationic trypsinogen. The inheritance pattern is autosomal dominant with an incomplete penetrance (80%). Since 1996, more than 30 mutations were found. The three more common mutations are R122H, N29I and A16V. First symptoms begin since childhood, mainly before 10 years old. Main symptoms are pancreatic pain and acute pancreatitis (>70%). CP morphological changes as pancreatic calcifications are diagnosed at a median age of 22-25 years. Exocrine and endocrine pancreatic insufficiency occurred in 34% and 26% at a median age of 29 and 38 years. No clinical differences exist according to the mutation type. No excess of mortality in hereditary pancreatitis population compared to general population was found, despite a real risk of cancer. The cumulative risks of pancreatic cancer at 50, 60 and, 75 years are 10%, 18.7% and, 53.5%, respectively. The relative risk of cancer increases in smokers and is evaluated to 8.55. Hereditary pancreatitis diagnosis permits to propose an adapted management in expert centres.

  5. [Latest advances in chronic pancreatitis].

    Science.gov (United States)

    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. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  6. [Latest advances in chronic pancreatitis].

    Science.gov (United States)

    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. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  7. Helicobacter pylori and pancreatic diseases

    Institute of Scientific and Technical Information of China (English)

    Milutin; Bulajic; Nikola; Panic; Johannes; Matthias; L?hr

    2014-01-01

    A possible role for Helicobacter pylori(H. pylori) infec-tion in pancreatic diseases remains controversial. H. pylori infection with antral predomination leading to an increase in pancreatic bicarbonate output and induc-ing ductal epithelial cell proliferation could contribute to the development of pancreatic cancer via complex interactions with the ABO genotype, dietary and smok-ing habits and N-nitrosamine exposure of the host. Although the individual study data available so far is inconsistent, several meta-analyses have reported an increased risk for pancreatic cancer among H. pylori seropositive individuals. It has been suggested that H. pylori causes autoimmune pancreatitis due to molecu-lar mimicry between H. pylori a-carbonic anhydrase(a-CA) and human CA type Ⅱ, and between H. pylori plasminogen-binding protein and human ubiquitin-protein ligase E3 component n-recognin 2, enzymes that are highly expressed in the pancreatic ductal andacinar cells, respectively. Future studies involving large numbers of cases are needed in order to examine the role of H. pylori in autoimmune pancreatitis more fully. Considering the worldwide pancreatic cancer burden, as well as the association between autoimmune pan-creatitis and other autoimmune conditions, a complete elucidation of the role played by H. pylori in the gen-esis of such conditions could have a substantial impact on healthcare.

  8. [Latest advances in acute pancreatitis].

    Science.gov (United States)

    de-Madaria, Enrique

    2015-09-01

    The present article analyses the main presentations on acute pancreatitis at Digestive Disease Week 2015. Arterial pseudoaneurysm is an uncommon complication of acute pancreatitis (incidence 0.7%) and mortality from this cause is currently anecdotal. Diabetes mellitus has little impact on the clinical course of acute pancreatitis, unlike cirrhosis, which doubles the risk of mortality. Intake of unsaturated fat could be associated with an increased severity of acute pancreatitis and is a confounding factor in studies evaluating the relationship between obesity and morbidity and mortality. PET-CT (positron emission tomography-computed tomography) could be a non-invasive tool to detect infection of collections in acute pancreatitis. Peripancreatic fat necrosis is less frequent than pancreatic fat necrosis and is associated with a better clinical course. If the clinical course is poor, increasing the calibre of the percutaneous drains used in the treatment of infected necrosis can avoid surgery in 20% of patients. The use of low molecular-weight heparin in moderate or severe pancreatitis could be associated with a better clinical course, specifically with a lower incidence of necrosis. In acute recurrent pancreatitis, simvastatin is a promising drug for prophylaxis of new episodes of acute pancreatitis. Nutritional support through a nasogastric tube does not improve clinical course compared with oral nutrition. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  9. Tratamiento nutricional de los enfermos con pancreatitis aguda: cuando el pasado es presente Nutritional management of patients with acute pancreatitis: when the past is present

    Directory of Open Access Journals (Sweden)

    A. García Almansa

    2008-05-01

    Full Text Available Los pacientes con pancreatitis aguda sufren con frecuencia un acusado deterioro de su estado nutricional. En algunos éste es ya anterior a su ingreso hospitalario, como ocurre en muchos casos de etiología alcohólica. En otras ocasiones la desnutrición se manifiesta posteriormente en el seno de una pancreatitis de larga evolución o complicada, que impide una correcta alimentación por un tiempo prolongado. A todo ello hay que sumar el hipercatabolismo proteico y el estrés que presentan estos enfermos. Es norma habitual en el tratamiento de la pancreatitis aguda mantener al enfermo en ayuno absoluto. En las pancreatitis leves este estado solo es necesario durante muy pocos días, iniciándose la realimentación por vía oral progresivamente, y no se requieren especiales cuidados nutricionales, salvo que presenten una desnutrición previa. Ahora bien, en los pacientes con pancreatitis moderada y/o grave en los que se prevé un ayuno prolongado por más de una semana, debemos siempre recurrir a un soporte nutricional artificial, que preserve el estado nutricional de estos enfermos, ya que no es suficiente la habitual reposición hidroelectrolítica. En este capítulo realizaremos una revisión actualizada del tratamiento nutricional en estas situaciones, intentando responder a diferentes preguntas entre las que se incluyen el tipo de soporte nutricional indicado, cuándo hay que instaurarlo y hasta qué momento.Patients with acute pancreatitis usually present nutritional status impairment. In alcoholic pancreatitis this impairment is usually presented before hospital admission. In patients with long-term complicated pancreatitis, malnutrition develops during the course of the disease. Besides, these patients present an increased stress and protein hypercatabolism. Treatment of acute pancreatitis usually maintains patients in a short period of starvation. In mild pancreatitis, starvation is needed for a few days, beginning progressively oral

  10. Endoscopic naso-pancreatic stent-guided single-branch resection of the pancreas for multiple intraductal papillary mucinous adenomas

    Institute of Scientific and Technical Information of China (English)

    Tamotsu Kuroki; Yoshitsugu Tajima; Ryuji Tsutsumi; Noritsugu Tsuneoka; Amane Kitasato; Tomohiko Adachi; Takashi Kanematsu

    2006-01-01

    In benign or low-grade malignant pancreatic tumors,complete removal of the lesion is sufficient for a cure,and thus minimal resection techniques with preservation of the pancreatic functional reserve have advantages over more extended pancreatic resections. However, a high incidence of postoperative pancreatic fistula in such procedures has been reported. Moreover, branch-type intraductal papillary mucinous neoplasms of the pancreas tend to locate in the head of the pancreas, and show less malignant potential. We describe an endoscopic nasopancreatic stent-guided single-branch resection of the pancreas for branch-type multiple intraductal papillary mucinous adenomas, along with a gastric wall-covering method for the prevention of pancreatic leakage.

  11. Mass preserving image registration

    DEFF Research Database (Denmark)

    Gorbunova, Vladlena; Sporring, Jon; Lo, Pechin Chien Pau

    2010-01-01

    The paper presents results the mass preserving image registration method in the Evaluation of Methods for Pulmonary Image Registration 2010 (EMPIRE10) Challenge. The mass preserving image registration algorithm was applied to the 20 image pairs. Registration was evaluated using four different...

  12. Modes of fossil preservation

    Science.gov (United States)

    Schopf, J.M.

    1975-01-01

    The processes of geologic preservation are important for understanding the organisms represented by fossils. Some fossil differences are due to basic differences in organization of animals and plants, but the interpretation of fossils has also tended to be influenced by modes of preservation. Four modes of preservation generally can be distinguished: (1) Cellular permineralization ("petrifaction") preserves anatomical detail, and, occasionally, even cytologic structures. (2) Coalified compression, best illustrated by structures from coal but characteristic of many plant fossils in shale, preserves anatomical details in distorted form and produces surface replicas (impressions) on enclosing matrix. (3) Authigenic preservation replicates surface form or outline (molds and casts) prior to distortion by compression and, depending on cementation and timing, may intergrade with fossils that have been subject to compression. (4) Duripartic (hard part) preservation is characteristic of fossil skeletal remains, predominantly animal. Molds, pseudomorphs, or casts may form as bulk replacements following dissolution of the original fossil material, usually by leaching. Classification of the kinds of preservation in fossils will aid in identifying the processes responsible for modifying the fossil remains of both animals and plants. ?? 1975.

  13. Long-Term Outcomes after Acute Necrotizing Pancreatitis: What Happens to the Pancreas and to the Patient?

    Directory of Open Access Journals (Sweden)

    Rafaela Cristina Goebel Winter Gasparoto

    2015-03-01

    Full Text Available Context Late consequences of acute pancreatitis have received little attention. It is controversial whether the pancreas fully recovers after an episode of acute pancreatitis, especially in the presence of necrosis. Therefore, the presence of late pancreatic dysfunction following acute necrotizing pancreatitis is uncertain and there are controversies about how it may affect long-term quality of life. Objectives To evaluate pancreatic function and morphology, besides quality of life, in patients with prior acute necrotizing pancreatitis. Patients Patients who were admitted to our hospital with acute necrotizing pancreatitis in a ten-year interval were identified and thirty-eight survivors were contacted to enroll in the study out of which sixteen patients were included. Methods Exocrine function was studied by qualitative fecal fat excretion. Endocrine function was evaluated by oral glucose tolerance test, HOMA-beta and C-peptide. Pancreatic morphology was examined by computed tomography. Quality of life was measured by 36-item short-form health survey. Tests were performed at leasttwelve months after the index episode of acute necrotizing pancreatitis. Results The prevalence of pancreatic exocrine insufficiency was 6.2%. Endocrine dysfunction was observed in half the cases, and no association with the extension of necrosis was found. Morphological changes were frequent (62.5% and more prevalent in those who faced extensive necrosis. Quality of life was considered good, and its impairment was found exclusively in mental health domain, markedly in patients who had alcoholic pancreatitis. There was no correlation between quality of life and prognostic indicators. Conclusions Exocrine function and quality of life were preserved in this group of patients. However, endocrine dysfunction and morphological abnormalities were frequent after acute necrotizing pancreatitis. These findings justify a long-term follow-up in order to initiate specific

  14. Long-term outcomes after acute necrotizing pancreatitis: what happens to the pancreas and to the patient?

    Science.gov (United States)

    Winter Gasparoto, Rafaela Cristina Goebel; Racy, Marcelo De Castro Jorge; De Campos, Tercio

    2015-03-20

    Late consequences of acute pancreatitis have received little attention. It is controversial whether the pancreas fully recovers after an episode of acute pancreatitis, especially in the presence of necrosis. Therefore, the presence of late pancreatic dysfunction following acute necrotizing pancreatitis is uncertain and there are controversies about how it may affect long-term quality of life. To evaluate pancreatic function and morphology, besides quality of life, in patients with prior acute necrotizing pancreatitis. Patients who were admitted to our hospital with acute necrotizing pancreatitis in a ten-year interval were identified and thirty-eight survivors were contacted to enroll in the study out of which sixteen patients were included. Exocrine function was studied by qualitative fecal fat excretion. Endocrine function was evaluated by oral glucose tolerance test, HOMA-beta and C-peptide. Pancreatic morphology was examined by computed tomography. Quality of life was measured by 36-item short-form health survey. Tests were performed at least twelve months after the index episode of acute necrotizing pancreatitis. The prevalence of pancreatic exocrine insufficiency was 6.2%. Endocrine dysfunction was observed in half the cases, and no association with the extension of necrosis was found. Morphological changes were frequent (62.5%) and more prevalent in those who faced extensive necrosis. Quality of life was considered good, and its impairment was found exclusively in mental health domain, markedly in patients who had alcoholic pancreatitis. There was no correlation between quality of life and prognostic indicators. Exocrine function and quality of life were preserved in this group of patients. However, endocrine dysfunction and morphological abnormalities were frequent after acute necrotizing pancreatitis. These findings justify a long-term follow-up in order to initiate specific treatment promptly.

  15. [Acute pancreatitis and pregnancy].

    Science.gov (United States)

    Scollo, P; Licitra, G

    1993-12-01

    Aetiologic factors (gallstones, hyperlipidemia I-IV, hypertriglyceridaemia) make their occurrence, mainly, in the third trimester of gestation. Two cases of acute pancreatitis in pregnancy are described; in both cases patients referred healthy diet, no habit to smoke and no previous episode of pancreatitis. An obstructive pathology of biliary tract was the aetiologic factor. Vomiting, upper abdominal pain are aspecific symptoms that impose a differential diagnosis with acute appendicitis, cholecystitis and obstructive intestinal pathology. Laboratory data (elevated serum amylase and lipase levels) and ultrasonography carry out an accurate diagnosis. The management of acute pancreatitis is based on the use of symptomatic drugs, a low fat diet alternated to the parenteral nutrition when triglycerides levels are more than 28 mmol/L. Surgical therapy, used only in case of obstructive pathology of biliary tract, is optimally collected in the third trimester or immediately after postpartum. Our patients, treated only medically, delivered respectively at 38th and 40th week of gestation. Tempestivity of diagnosis and appropriate therapy permit to improve prognosis of a pathology that, although really associated with pregnancy, presents high maternal mortality (37%) cause of complications (shock, coagulopathy, acute respiratory insufficiency) and fetal (37.9%) by occurrence of preterm delivery.

  16. Fertility Preservation for Female

    Institute of Scientific and Technical Information of China (English)

    Jack Huang; Seang Lin Tan; Ri-Cheng Chian

    2006-01-01

    Preservation of female fertility is an important issue today. However, there are few effective clinical options for preserving female fertility. Firstly, conventional in vitro fertilization (IVF) followed by embryo cryopreservation is an accepted procedure but is not applicable to all women. Embryo freezing is suitable only for women with a male partner and may not be acceptable to some patients due to moral and religious reasons. Ovarian tissue freezing is another option of female fertility preservation but is an invasive procedure and the efficacy of this technique remains to be determined.Oocyte cryopreservation is also method for fertility preservation. Egg freezing is minimally invasive and can avoid the ethical and moral concerns related to cryopreservation of embryos. However, conventional slow freezing/rapid thawing methods are associated with low survival of oocytes. Recent development in vitrification of oocytes appears promising. Therefore, vitrification of unfertilized eggs may be a novel method to preserve female fertility.

  17. Self-preserving cosmetics.

    Science.gov (United States)

    Varvaresou, A; Papageorgiou, S; Tsirivas, E; Protopapa, E; Kintziou, H; Kefala, V; Demetzos, C

    2009-06-01

    Preservatives are added to products for two reasons: first, to prevent microbial spoilage and therefore to prolong the shelf life of the product; second, to protect the consumer from a potential infection. Although chemical preservatives prevent microbial growth, their safety is questioned by a growing segment of consumers. Therefore, there is a considerable interest in the development of preservative-free or self-preserving cosmetics. In these formulations traditional/chemical preservatives have been replaced by other cosmetic ingredients with antimicrobial properties that are not legislated as preservatives according to the Annex VI of the Commission Directive 76/768/EEC and the amending directives (2003/15/EC, 2007/17/EC and 2007/22/EC). 'Hurdle Technology', a technology that has been used for the control of product safety in the food industry since 1970s, has also been applied for the production of self-preserving cosmetics. 'Hurdle Technology' is a term used to describe the intelligent combination of different preservation factors or hurdles to deteriorate the growth of microorganisms. Adherence to current good manufacturing practice, appropriate packaging, careful choice of the form of the emulsion, low water activity and low or high pH values are significant variables for the control of microbial growth in cosmetic formulations. This paper describes the application of the basic principles of 'Hurdle Technology' in the production of self-preserving cosmetics. Multifunctional antimicrobial ingredients and plant-derived essential oils and extracts that are used as alternative or natural preservatives and are not listed in Annex VI of the Cosmetic Directive are also reported.

  18. Pancreatic and peri-pancreatic lesions mimic pancreatic islet cell tumor in multidetector computed tomography

    Institute of Scientific and Technical Information of China (English)

    XUE Hua-dan; LIU Wei; XIAO Yu; SUN Hao; WANG Xuan; LEI Jing; JIN Zheng-yu

    2011-01-01

    Objective This pictorial review aimed to summarize the most possible differential diagnosis of pancreatic islet cell tumor (PICT).Data sources Data used in this review were mainly from Medline and Pubmed in English. And all clinical images in this review were from Department of Radiology, Peking Union Medical College Hospital, Beijing, China.Study selection Cases of pancreatic cystadenoma, solid pseudo-papillary tumor of the pancreas, pancreatic metastasis, pancreatic adenocarcinoma, para-pancreatic neuroendocrine tumors, Castleman disease, gastrointestinal stromal tumor, splenic artery aneurysm and accessory spleen were selected in this pictorial review for differential diagnosis of PICT.Results Careful analysis of imaging features and correlation with the clinical manifestations may allow a more specific diagnosis. It is also important that the radiologist is familiar with the anatomic variants and disease entities which mimic pancreatic islet cell tumor in order to avoid an improper treatment protocol.Conclusions Many congenital anatomic variants or other pancreatic and peri-pancreatic diseases may mimic MDCT appearance of pancreatic islet cell tumor. Radiological, clinical and pathological characteristics should be considered for the final diagnosis.

  19. Carbohydrate markers of pancreatic cancer.

    Science.gov (United States)

    Szajda, Sławomir Dariusz; Waszkiewicz, Napoleon; Chojnowska, Sylwia; Zwierz, Krzysztof

    2011-01-01

    Pancreatic cancer is the fourth most common cause of death from cancer in the world and the sixth in Europe. Pancreatic cancer is more frequent in males than females. Worldwide, following diagnosis of pancreatic cancer, <2% of patients survive for 5 years, 8% survive for 2 years and <50% survive for only approx. 3 months. The biggest risk factor in pancreatic cancer is age, with a peak of morbidity at 65 years. Difficulty in the diagnosis of pancreatic cancer causes a delay in its detection. It is one of the most difficult cancers to diagnose and therefore to treat successfully. Additional detection of carbohydrate markers may offer a better diagnosis of pancreatic cancer. Carbohydrate markers of cancer may be produced by the cancer itself or by the body in response to cancer, whose presence in body fluids suggests the presence and growth of the cancer. The most widely used, and best-recognized, carbohydrate marker of pancreatic cancer is CA 19-9 [CA (carbohydrate antigen) 19-9]. However, the relatively non-specific nature of CA 19-9 limits its routine use in the early diagnosis of pancreatic cancer, but it may be useful in monitoring treatment of pancreatic cancer (e.g. the effectiveness of chemotherapy), as a complement to other diagnostic methods. Some other carbohydrate markers of pancreatic cancer may be considered, such as CEA (carcinoembryonic antigen), CA 50 and CA 242, and the mucins MUC1, MUC2 and MUC5AC, but enzymes involved in the processing of glycoconjugates could also be involved. Our preliminary research shows that the activity of lysosomal exoglycosidases, including HEX (N-acetyl-β-D-hexosaminidase), GAL (β-D-galactosidase), FUC (α-L-fucosidase) and MAN (α-D-mannosidase), in serum and urine may be used in the diagnosis of pancreatic cancer.

  20. Comparative effects of pioglitazone and rosiglitazone on plasma levels of soluble receptor for advanced glycation end products in type 2 diabetes mellitus patients.

    Science.gov (United States)

    Oz Gul, Ozen; Tuncel, Ercan; Yilmaz, Yusuf; Ulukaya, Engin; Gul, Cuma Bulent; Kiyici, Sinem; Oral, Arzu Yilmaztepe; Guclu, Metin; Ersoy, Canan; Imamoglu, Sazi

    2010-01-01

    Low levels of soluble receptor for advanced glycation end products (sRAGE) have been associated with the occurrence of vascular complications in patients with type 2 diabetes mellitus. Preliminary evidence has suggested that thiazolidinediones have the ability to modulate circulating levels of this molecule in the hyperglycemic milieu. The aim of this pilot study was to assess the differential effect of 2 different thiazolidinediones-pioglitazone and rosiglitazone-on plasma levels of sRAGE in type 2 diabetes mellitus patients. Sixty type 2 diabetes mellitus subjects were randomly assigned to receive pioglitazone (30 mg/d, n = 19), rosiglitazone (4 mg/d, n = 20), or placebo (medical nutrition therapy, n = 21) for 12 weeks. Changes in plasma glucose, glycosylated hemoglobin, insulin resistance (homeostasis model assessment), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and sRAGE were evaluated at baseline and after 12 weeks. At 12 weeks, the pioglitazone (P diabetes mellitus patients, pioglitazone-but not rosiglitazone-significantly raised sRAGE, which may contribute to its antiatherogenic effects.

  1. The Adipose Tissue Endocrine Mechanism of the Prophylactic Protective Effect of Pioglitazone in High-Fat Diet-Induced Insulin Resistance

    National Research Council Canada - National Science Library

    Gong, Y; Li, J; Li, C; Mu, Y; Xiao, Y; Tian, H; Pan, C; Liu, Y

    2012-01-01

    ...), or a high-fat diet plus treatment with pioglitazone (P group). Glucose tolerance and insulin resistance were tested at weeks 10 and 11 after starting the diet and, at week 12, adipose, liver and skeletal muscle tissue samples were taken...

  2. A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression

    Directory of Open Access Journals (Sweden)

    Todd D. Levine

    2012-01-01

    Full Text Available Objectives. To determine if therapy with pioglitazone HCl and tretinoin could slow disease progression in patients with ALS. Levels of tau and pNFH in the cerebrospinal fluid were measured to see if they could serve as prognostic indicators. Methods. 27 subjects on stable doses of riluzole were enrolled. Subjects were randomized to receive pioglitazone 30 mg/d and tretinoin 10 mg/BID for six months or two matching placebos. ALSFRS-R scores were followed monthly. At baseline and at the final visit, lumbar punctures (LPs were performed to measure cerebrospinal fluid (CSF biomarker levels. Results. Subjects treated with tretinoin, pioglitazone, and riluzole had an average rate of decline on the ALSFRS-R scale of −1.02 points per month; subjects treated with placebo and riluzole had a rate of decline of -.86 (P=.18. Over six months of therapy, CSF tau levels decreased in subjects randomized to active treatment and increased in subjects on placebo. Further higher levels of pNF-H at baseline correlated with a faster rate of progression. Conclusion. ALS patients who were treated with tretinoin and pioglitazone demonstrated no slowing on their disease progression. Interestingly, the rate of disease progression was strongly correlated with levels of pNFH in the CSF at baseline.

  3. A randomized placebo-controlled study on the effects of pioglitazone on cortisol metabolism in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Hermann, Anne Pernille; Hagen, Claus

    2009-01-01

    OBJECTIVE: To investigate possible effects of insulin-sensitizing treatment on cortisol metabolism in insulin-resistant patients with polycystic ovary syndrome (PCOS). DESIGN: Randomized placebo-controlled study. SETTING: Academic tertiary care medical center. PATIENT(S): Thirty insulin-resistant......OBJECTIVE: To investigate possible effects of insulin-sensitizing treatment on cortisol metabolism in insulin-resistant patients with polycystic ovary syndrome (PCOS). DESIGN: Randomized placebo-controlled study. SETTING: Academic tertiary care medical center. PATIENT(S): Thirty insulin......-resistant PCOS patients. INTERVENTION(S): Sixteen weeks of pioglitazone (30 mg/day) or placebo treatment. MAIN OUTCOME MEASURE(S): Twenty-four-hour 20 min integrated blood sampling for measurement of cortisol and 24 h urinary excretion of steroid metabolites. Relative 5alpha-reductase activity was evaluated...... levels. Delta A/E ratio inversely correlated with Delta IGF-I and Delta peak GH during GH stimulation tests. No significant changes were measured in T, DHT, DHEA, DHEAS, 24 h mean cortisol, or urinary excretion of steroid metabolites. CONCLUSION(S): Pioglitazone decreased relative 5alpha...

  4. Development, optimization and in vitro-in vivo evaluation of pioglitazone- loaded jackfruit seed starch-alginate beads.

    Science.gov (United States)

    Nayak, Amit Kumar; Pal, Dilipkumar; Hasnain, Saquib Md

    2013-10-01

    The present investigation describes development and optimization of pioglitazone-loaded jackfruit seed starch (JFSS)-alginate beads by ionotropic-gelation using 3(2) factorial design. The effect of polymer-blend ratio and CaCl2 concentration on the drug encapsulation efficiency (DEE, %), and cumulative drug release after 10 hours (R10h, %) was optimized. The DEE (%) of these beads were 64.80 ± 1.92 to 94.07 ± 3.82 % with sustained in vitro drug release of 64.± 1.83 to 92.66 ± 4.54 % over 10 hours. The in vitro drug release from these beads followed controlled-release pattern with super case-II transport. Particle size range of these beads was 0.77 ± 0.04 to 1.24 ± 0.09 mm. The beads were also characterized by SEM and FTIR. The swelling of these beads was influenced by pH of the test medium. The optimized pioglitazone-loaded JFSS-alginate beads showed significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration.

  5. A COMPARATIVE STUDY OF ROSIGLITAZONE AND PIOGLITAZONE TO EVALUATE THE CARDIOVASCULAR EFFECTS IN HIGH FRUCTOSE DIET INDUCED HYPERTENSIVE RATS

    Directory of Open Access Journals (Sweden)

    Arghya Biswas et al

    2012-09-01

    Full Text Available Thiazolidinediones (TZDs were widely used for the treatment of type 2 diabetes. Recent studies have shown that TZDs have paradoxical effects on cardiovascular diseases. The objective of the present study was to investigate the effect of TZDs (Rosiglitazone and Pioglitazone in High Fructose Diet (HFD induced hypertension in rats. HFD was given for 14 weeks. After 8 weeks of hypertension induction period, treatment phase was started with Rosiglitazone (ROSI 10 and 30 mg/kg, p.o. and Pioglitazone (PIO 10 and 30 mg/kg, p.o. to the respective groups which were continued till 6 weeks. Systolic Blood Pressure (SBP was measured weekly and serum glucose, triglyceride, cholesterol and HDL-C were measured at the end of study period. In HFD fed rats hypertension was observed after 8 weeks. Treatment with the test drugs significantly reversed the changes in serum enzyme levels as well as SBP made by HFD feeding compared to the control group. The study concludes that TZDs possess antihypertensive effect as exhibited in the present experimental settings.

  6. Possible Involvement of Pancreatic Fatty Infiltration in Pancreatic Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Mika Hori

    2016-03-01

    Full Text Available Pancreatic cancer is difficult to diagnose in its early stage and is one of the most lethal human cancers. Thus, it is important to clarify its major risk factors, predictive factors and etiology. Here, we focus on fatty infiltration of the pancreas and suggest that it could be a risk factor for pancreatic cancer. Fatty infiltration of the pancreas is observed as ectopic adipocytes infiltrating the pancreatic tissue and is positively correlated with obesity and the prevalence of diabetes mellitus, which are risk factors for pancreatic cancer. However, whether fatty infiltration is a major risk factor for pancreatic cancer has not been established. Recent clinical studies show there is a positive correlation between fatty infiltration of the pancreas and pancreatic precancerous lesions or ductal adenocarcinomas. Animal experimental studies also show an association between fatty infiltration of the pancreas and pancreatic precancerous lesions or ductal adenocarcinomas development. Syrian golden hamsters, which are sensitive to chemical carcinogens in the pancreas, develop fatty infiltration of the pancreas with age. The combination of a high-fat diet and a chemical carcinogen that induces a K-ras mutation increases the severity of fatty infiltration of the pancreas. Thus, fatty infiltration of the pancreas is suggested to promote pancreatic carcinogenesis via a K-ras activating mutation. It is assumed that increased expression of adipokines and of inflammatory and proliferation-associated factors elicited by fatty infiltration of the pancreas may contribute to pancreatic precancerous lesions or ductal adenocarcinomas development. Accumulating evidence suggests that in addition to suppression of Ras activation, methods to modulate fatty infiltration in the pancreas can be considered as a strategy for preventing pancreatic cancer.

  7. Groove pancreatitis: A rare form of chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Bharivi Jani

    2015-01-01

    Full Text Available 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

  8. Acute pancreatitis in patients with pancreatic cancer

    Science.gov (United States)

    Li, Shaojun; Tian, Bole

    2017-01-01

    Abstract Acute pancreatitis (AP) is a rare manifestation of pancreatic cancer (PC). The relationship between AP and PC remains less distinct. From January 2009 to November 2015, 47consecutive patients with PC who presented with AP were reviewed for this study. Clinical features, clinicopathologic variables, postoperative complications, and follow-up evaluations of patients were documented in detail from our database. In order to identify cutoff threshold time for surgery, receiver operating curve (ROC) was built according to patients with or without postoperative complications. Cumulative rate of survival was calculated by using the Kaplan–Meier method. The study was conducted in accordance with the principles of the Declaration of Helsinki and the guidelines of West China Hospital. This study included 35 men (74.5%) and 12 women (25.5%) (mean age: 52 years), with a median follow-up of 40 months. AP was clinically mild in 45 (95.7%) and severe in 2 (4.3%). The diagnosis of PC was delayed by 2 to 660 days (median 101 days). Thirty-nine (83.0%) cases underwent surgery. Eight (17.0%) cases performed biopsies only. Of 39 patients, radical surgery was performed in 32 (82.1%) cases and palliative in 7 (19.9%) cases. Two (8.0%) patients were needed for vascular resection and reconstruction. Postoperative complications occurred in 12 (30.8%) patients. About 24.5 days was the best cutoff point, with an area under curve (AUC) of 0.727 (P = 0.025, 95% confidence interval: 0.555–0.8999). The survival rate of patients at 1 year was 23.4%. The median survival in patients with vascular resection and reconstruction was 18 months, compared with 10 months in patients without vascular resection (P = 0.042). For the primary stage (T), Tix was identified in 3 patients, the survival of whom were 5, 28, 50 months, respectively. And 2 of them were still alive at the follow-up period. The severity of AP was mainly mild. Surgical intervention after 24.5 days may benefit for

  9. Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in drug-naive subjects with type 2 diabetes.

    Science.gov (United States)

    Bi, Yan; Zhang, Bing; Xu, Wen; Yang, Huijie; Feng, Wenhuan; Li, Cuiliu; Tong, Guoyu; Li, Ming; Wang, Xin; Shen, Shanmei; Zhu, Bin; Weng, Jianping; Zhu, Dalong

    2014-10-01

    Ectopic accumulation of lipids in nonadipose tissues plays a primary role in the pathogenesis of type 2 diabetes mellitus (T2DM). This study was to examine the effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in T2DM. Thirty-three drug-naive T2DM patients (age 52.7 ± 1.7 years, HbA1c 8.7 ± 0.2 %, body mass index 24.5 ± 0.5 kg/m(2)) were randomized into exenatide, insulin, or pioglitazone for 6 months. Intrahepatic fat (IHF), visceral fat (VF), and subcutaneous fat (SF) were measured using proton nuclear magnetic resonance spectroscopy. Plasma tumor necrosis factor α (TNFα) and adiponectin were assayed by ELISA. HbA1c declined significantly in all three groups. Body weight, waist, and serum triglycerides decreased with exenatide. After interventions, IHF significantly reduced with three treatments (exenatide Δ = -68 %, insulin Δ = -58 %, pioglitazone Δ = -49 %). Exenatide reduced VF (Δ = -36 %) and SF (Δ = -13 %), and pioglitazone decreased VF (Δ = -30 %) with no impact on SF, whereas insulin had no impact on VF or SF. Levels of TNFα (exenatide/insulin/pioglitazone) decreased, and levels of adiponectin (exenatide/pioglitazone) increased. Analysis showed that ΔIHF correlated with ΔHbA1c and Δweight. Besides, ΔIHF correlated with Δtriglycerides and ΔTNFα, but the correlations fell short of significance after BMI adjustment. By linear regression analysis, ΔHbA1c alone explained 41.5 % of the variance of ΔIHF, and ΔHbA1c + Δweight explained 57.6 % of the variance. Liver fat content can be significantly reduced irrespective of using exenatide, insulin, and pioglitazone. Early glycaemic control plays an important role in slowing progression of fatty liver in T2DM.

  10. Canagliflozin-Associated Acute Pancreatitis.

    Science.gov (United States)

    Verma, Rajanshu

    2016-01-01

    Canagliflozin is a new drug in class of sodium-glucose cotransporter 2 inhibitors used for treatment of type 2 diabetes mellitus. We describe a patient who developed moderately severe acute pancreatitis as an untoward consequence after being initiated on this drug. To the best of our knowledge, this is the first reported case of canagliflozin-associated acute pancreatitis in clinical literature.

  11. Pathologic pancreatic endocrine cell hyperplasia

    Institute of Scientific and Technical Information of China (English)

    Debra Ouyang; Deepti Dhall; Run Yu

    2011-01-01

    Pathologic hyperplasia of various pancreatic endocrine cells is rare but has been long known. β cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia of infancy, which is commonly caused by mutations in the islet ATP-sensitive potassium channel, and to noninsulinoma pancreatogenous hypoglycemia in adults,which may or may not be associated with bariatric surgery.α cell hyperplasia may cause glucagonoma syndrome or induce pancreatic neuroendocrine tumors. An inactivating mutation of the glucagon receptor causes α cell hyperplasia and asymptomatic hyperglucagonemia.Pancreatic polypeptide cell hyperplasia has been described without a clearly-characterized clinical syndrome and hyperplasia of other endocrine cells inside the pancreas has not been reported to our knowledge.Based on morphological evidence, the main pathogenetic mechanism for pancreatic endocrine cell hyperplasia is increased endocrine cell neogenesis from exocrine ductal epithelium. Pancreatic endocrine cell hyperplasia should be considered in the diagnosis and management of hypoglycemia, elevated islet hormone levels,and pancreatic neuroendocrine tumors. Further studies of pathologic pancreatic endocrine cell hyperplasia will likely yield insights into the pathogenesis and treatment of diabetes and pancreatic neuroendocrine tumors.

  12. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

    Bang, Ulrich-Christian; Semb, Synne; Nojgaard, Camilla

    2008-01-01

    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may...

  13. Pathologic pancreatic endocrine cell hyperplasia

    Science.gov (United States)

    Ouyang, Debra; Dhall, Deepti; Yu, Run

    2011-01-01

    Pathologic hyperplasia of various pancreatic endocrine cells is rare but has been long known. β cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia of infancy, which is commonly caused by mutations in the islet ATP-sensitive potassium channel, and to non-insulinoma pancreatogenous hypoglycemia in adults, which may or may not be associated with bariatric surgery. α cell hyperplasia may cause glucagonoma syndrome or induce pancreatic neuroendocrine tumors. An inactivating mutation of the glucagon receptor causes α cell hyperplasia and asymptomatic hyperglucagonemia. Pancreatic polypeptide cell hyperplasia has been described without a clearly-characterized clinical syndrome and hyperplasia of other endocrine cells inside the pancreas has not been reported to our knowledge. Based on morphological evidence, the main pathogenetic mechanism for pancreatic endocrine cell hyperplasia is increased endocrine cell neogenesis from exocrine ductal epithelium. Pancreatic endocrine cell hyperplasia should be considered in the diagnosis and management of hypoglycemia, elevated islet hormone levels, and pancreatic neuroendocrine tumors. Further studies of pathologic pancreatic endocrine cell hyperplasia will likely yield insights into the pathogenesis and treatment of diabetes and pancreatic neuroendocrine tumors. PMID:21245985

  14. Pancreatic adenocarcinoma pathology : changing "landscape"

    NARCIS (Netherlands)

    Brosens, Lodewijk A A; Hackeng, Wenzel M; Offerhaus, G Johan; Hruban, Ralph H; Wood, Laura D

    2015-01-01

    Pancreatic cancer is a devastating disease. At time of diagnosis the disease is usually advanced and only a minority of patients are eligible for surgical resection. The overall 5-year survival is 6%. However, survival of patients with early stage pancreatic cancer is significantly better. To improv

  15. Diet and Pancreatic Cancer Prevention.

    Science.gov (United States)

    Casari, Ilaria; Falasca, Marco

    2015-11-23

    Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer.

  16. Diet and Pancreatic Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Ilaria Casari

    2015-11-01

    Full Text Available Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer.

  17. Chronopolis Digital Preservation Network

    Directory of Open Access Journals (Sweden)

    David Minor

    2010-07-01

    Full Text Available The Chronopolis Digital Preservation Initiative, one of the Library of Congress’ latest efforts to collect and preserve at-risk digital information, has completed its first year of service as a multi-member partnership to meet the archival needs of a wide range of domains.Chronopolis is a digital preservation data grid framework developed by the San Diego Supercomputer Center (SDSC at UC San Diego, the UC San Diego Libraries (UCSDL, and their partners at the National Center for Atmospheric Research (NCAR in Colorado and the University of Maryland's Institute for Advanced Computer Studies (UMIACS.Chronopolis addresses a critical problem by providing a comprehensive model for the cyberinfrastructure of collection management, in which preserved intellectual capital is easily accessible, and research results, education material, and new knowledge can be incorporated smoothly over the long term. Integrating digital library, data grid, and persistent archive technologies, Chronopolis has created trusted environments that span academic institutions and research projects, with the goal of long-term digital preservation.A key goal of the Chronopolis project is to provide cross-domain collection sharing for long-term preservation. Using existing high-speed educational and research networks and mass-scale storage infrastructure investments, the partnership is leveraging the data storage capabilities at SDSC, NCAR, and UMIACS to provide a preservation data grid that emphasizes heterogeneous and highly redundant data storage systems.In this paper we will explore the major themes within Chronopolis, including:a The philosophy and theory behind a nationally federated data grid for preservation. b The core tools and technologies used in Chronopolis. c The metadata schema that is being developed within Chronopolis for all of the data elements. d Lessons learned from the first year of the project.e Next steps in digital preservation using Chronopolis: how we

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

    Directory of Open Access Journals (Sweden)

    Peter Feick

    2010-03-01

    Full Text Available : 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.

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

    Science.gov (United States)

    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

  20. Clinical application of serial operations with preserving spleen

    Institute of Scientific and Technical Information of China (English)

    Hong-Chi Jiang; Bei Sun; Hai-Quan Qiao; Jun Xu; Da-Xun Piao; Hang Yin

    2001-01-01

    AIM: To evaluate the clinical application of serial operations with preservation of spleen. METHODS: Serial operations with preserving spleen were performed on 211 cases in our hospital from 1980 to 2000.The patient's age ranged from 13 to 56 years, averaging 3years. Diseases included splenic injury in 171 cases, portal hypertension in 9 cases, splenic cyst in 10 cases, and the lesion of pancreatic body and tail in 21 cases. RESULTS: All the cases were cured, and 129 patients were followedup from 3 months to 3 years with the leukocyte phagocytosis test, detection of immunoglubin, CT, 99mTc scanning and ultrasonogrsphy. The results were satisfactory. CONCLUSION: The operations with preserving spleen were safe, feasible, and worth of clinical application.

  1. Pharmacological challenges in chronic pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Brokjaer, Anne; Fischer, Iben Wendelboe Deleuran

    2014-01-01

    Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion....... Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases...... food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids...

  2. Modification of MCF-10A cells with pioglitazone and serum-rich growth medium increases soluble factors in the conditioned medium, likely reducing BT-474 cell growth.

    Science.gov (United States)

    Khoo, Boon Yin; Miswan, Noorizan; Balaram, Prabha; Nadarajan, Kalpanah; Elstner, Elena

    2012-01-01

    In the present study, we aimed to preincubate MCF-10A cells with pioglitazone and/or serum-rich growth media and to determine adhesive and non-adhesive interactions of the preincubated MCF-10A cells with BT-474 cells. For this purpose, the MCF-10A cells were preincubated with pioglitazone and/or serum-rich growth media, at appropriate concentrations, for 1 week. The MCF-10A cells preincubated with pioglitazone and/or serum-rich growth media were then co-cultured adhesively and non-adhesively with BT-474 cells for another week. Co-culture of BT-474 cells with the preincubated MCF-10A cells, both adhesively and non-adhesively, reduced the growth of the cancer cells. The inhibitory effect of the preincubated MCF-10A cells against the growth of BT-474 cells was likely produced by increasing levels of soluble factors secreted by the preincubated MCF-10A cells into the conditioned medium, as immunoassayed by ELISA. However, only an elevated level of a soluble factor distinguished the conditioned medium collected from the MCF-10A cells preincubated with pioglitazone and serum-rich growth medium than that with pioglitazone alone. This finding was further confirmed by the induction of the soluble factor transcript expression in the preincubated MCF-10A cells, as determined using real-time PCR, for the above phenomenon. Furthermore, modification of the MCF-10A cells through preincubation did not change the morphology of the cells, indicating that the preincubated cells may potentially be injected into mammary fat pads to reduce cancer growth in patients or to be used for others cell-mediated therapy.

  3. STUDIES ON LINEARTY AND ASSAY USING RP-HPLC AND UV-VISIBLE SPECTROSCOPY FOR THE DRUGS OXCARBAZEPINE AND PIOGLITAZONE BEFORE AND AFTER EXPIRY PERIOD

    Directory of Open Access Journals (Sweden)

    S. Suganya, A. Bright and T.S. Renuga Devi*

    2012-06-01

    Full Text Available The standard for stability and quality of drugs for approval of marketing, are assured by testing and systematic evaluation using different analytical techniques. The drugs are tested in pharma analytical lab involving analysts associated spectra, chromatogram etc , and the results are analyzed leading to fixation of expiry dates. Once the drug crosses its expiry period, its potency is lost and it deteriorates, not only decreasing in therapeutic activity but also turning to be toxic. In the present investigation RP-HPLC and UV-Visible spectroscopic methods are employed for estimation of drugs oxcarbazepine and pioglitazone in tablet dosage form before expiry period and 10-12 months after its expiry. Chromatography was carried out on a C-18 column using a mobile phase of 0.05M KH2PO4 and 0.5 ml Triethylamine buffer solution: methanol: acetonitrile (60:20:20 v/v for oxcarbazepine. The flow rate was 1ml/min with detection at 254nm. For pioglitazone a mobile phase of 0.02 M KH2PO4 buffer: acetonitrile (50:50v/v was used. The flow rate was 2ml/min with detection at 270nm.The calibration curves obtained using HPLC method was linear in the range 160 - 240μgml-1 for oxcarbazepine and 170-280 μgml-1 for pioglitazone. The calibration curves obtained using UV-Visible spectroscopy was linear in the range 10-30 μgml-1 for oxcarbazepine and 10-34 μgml-1 for pioglitazone. Assays of oxcarbazepine found using HPLC technique before expiry was 152.05mg/tablet and after expiry were 138.50mg/tablet. For pioglitazone, before expiry it was 30.85mg/tablet and after expiry 27.60mg/tablet. This was substantiated using UV-Visible spectroscopy.

  4. Influence of health warnings on the use of rosiglitazone and pioglitazone in an area of Spain: A time-series study

    Directory of Open Access Journals (Sweden)

    Eduardo Carracedo-Martínez

    2016-08-01

    Full Text Available Background: Throughout 2007 and January 2008, several glitazones health warnings were published on rosiglitazone myocardial infarction risk. The impact of such warnings on glitazones prevalence of utilization has been extensively studied in the United States but only in one European country (England, which has showed different pattern from US studies. The aim of this study is to evaluate the impact of such safety warnings on glitazones utilization in an area of another European country. Methods: We calculated the number of defined daily doses per thousand inhabitants per day of glitazones each month during the period from 2006 to 2008 in a health area of Spain. We analyzed the data graphically and through a segmented regression analysis. Results: Rosiglitazone defined daily doses per thousand inhabitants per day were growing before the safety warnings, after the warnings a change in trend occurred and rosiglitazone utilization showed a downturn slope. Pioglitazone defined daily doses per thousand inhabitants per day were stable before the safety warnings, and a linear growth was observed after the safety warnings. Throughout the study period, rosiglitazone defined daily doses per thousand inhabitants per day were higher than pioglitazone defined daily doses per thousand inhabitants per day until near the end of 2008. Conclusion: Despite the fact that cardiovascular warnings affected rosiglitazone and not pioglitazone, rosiglitazone was more utilized than pioglitazone until near the end of 2008 which is a pattern similar to the one found in another European studies in England, but very different from studies in the United States, where rosiglitazone was less utilized than pioglitazone from the first month after rosiglitazone cardiovascular safety warnings.

  5. Pioglitazone normalizes insulin signaling in the diabetic rat retina through reduction in tumor necrosis factor α and suppressor of cytokine signaling 3.