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Sample records for pancreatic lipase inhibitory

  1. Secoiridoids from the stem barks of Fraxinus rhynchophylla with pancreatic lipase inhibitory activity.

    PubMed

    Ahn, Jong Hoon; Shin, Eunjin; Liu, Qing; Kim, Seon Beom; Choi, Kyeong-Mi; Yoo, Hwan-Soo; Hwang, Bang Yeon; Lee, Mi Kyeong

    2013-01-01

    Pancreatic lipase digests dietary fats by hydrolysis, which is a key enzyme for lipid absorption. Therefore, reduction of fat absorption by the inhibition of pancreatic lipase is suggested to be a therapeutic strategy for obesity. From the EtOAc-soluble fraction of the stem barks of Fraxinus rhynchophylla (Oleaceae), four secoiridoids such as ligstroside (1), oleuropein (2), 2"-hydroxyoleuropein (3) and hydroxyframoside B (4) were isolated. The inhibitory activity of these compounds on pancreatic lipase was assessed using porcine pancreatic lipase as an in vitro assay system. Compound 4 showed the strongest inhibition on pancreatic lipase, which followed by compounds 1-3. In addition, compound 4 exerted inhibitory effect on pancreatic lipase in a mixed mechanism of competitive and noncompetitive manner. Taken together, F. rhynchophylla and its constituents might be beneficial to obesity.

  2. Pancreatic lipase inhibitory activity of taraxacum officinale in vitro and in vivo

    PubMed Central

    Zhang, Jian; Kang, Min-Jung; Kim, Myung-Jin; Kim, Mi-Eun; Song, Ji-Hyun; Lee, Young-Min

    2008-01-01

    Obesity has become a worldwide health problem. Orlistat, an inhibitor of pancreatic lipase, is currently approved as an anti-obesity drug. However, gastrointestinal side effects caused by Orlistat may limit its use. In this study the inhibitory activities of dandelion (Taraxacum officinale) against pancreatic lipase in vitro and in vivo were measured to determine its possible use as a natural anti-obesity agent. The inhibitory activities of the 95% ethanol extract of T. officinale and Orlistat were measured using 4-methylumbelliferyl oleate (4-MU oleate) as a substrate at concentrations of 250, 125, 100, 25, 12.5 and 4 µg/ml. To determine pancreatic lipase inhibitory activity in vivo, mice (n=16) were orally administered with corn oil emulsion (5 ml/kg) alone or with the 95% ethanol extract of T. officinale (400 mg/kg) following an overnight fast. Plasma triglyceride levels were measured at 0, 90, 180, and 240 min after treatment and incremental areas under the response curves (AUC) were calculated. The 95% ethanol extract of T. officinale and Orlistat, inhibited, porcine pancreatic lipase activity by 86.3% and 95.7% at a concentration of 250 µg/ml, respectively. T. officinale extract showed dose-dependent inhibition with the IC50 of 78.2 µg/ml. A single oral dose of the extract significantly inhibited increases in plasma triglyceride levels at 90 and 180 min and reduced AUC of plasma triglyceride response curve (p<0.05). The results indicate that T. officinale exhibits inhibitory activities against pancreatic lipase in vitro and in vivo. Further studies to elucidate anti-obesity effects of chronic consumption of T. officinale and to identify the active components responsible for inhibitory activity against pancreatic lipase are necessary. PMID:20016719

  3. Pancreatic lipase inhibitory constituents from Morus alba leaves and optimization for extraction conditions.

    PubMed

    Jeong, Ji Yeon; Jo, Yang Hee; Kim, Seon Beom; Liu, Qing; Lee, Jin Woo; Mo, Eun Jin; Lee, Ki Yong; Hwang, Bang Yeon; Lee, Mi Kyeong

    2015-06-01

    The leaves of Morus alba (Moraceae) have been traditionally used for the treatment of metabolic diseases including diabetes and hyperlipidemia. Thus, inhibitory effect of M. alba leaves on pancreatic lipase and their active constituents were investigated in this study. Twenty phenolic compounds including ten flavonoids, eight benzofurans, one stilbene and one chalcones were isolated from the leaves of M. alba. Among the isolated compounds, morachalcone A (20) exerted strong pancreatic lipase inhibition with IC50 value of 6.2 μM. Other phenolic compounds containing a prenyl group showed moderate pancreatic lipase inhibition with IC50 value of <50 μM. Next, extraction conditions with maximum pancreatic lipase inhibition and phenolic content were optimized using response surface methodology with three-level-three-factor Box-Behnken design. Our results suggested the optimized extraction condition for maximum pancreatic lipase inhibition and phenolic content as ethanol concentration of 74.9%; temperature 57.4 °C and sample/solvent ratio, 1/10. The pancreatic lipase inhibition and total phenolic content under optimized condition were found to be 58.5% and 26.2 μg GAE (gallic acid equivalent)/mg extract, respectively, which were well matched with the predicted value. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Potential pancreatic lipase inhibitory activity of an endophytic Penicillium species.

    PubMed

    Gupta, Mahiti; Saxena, Sanjai; Goyal, Dinesh

    2015-02-01

    Pancreatic lipase (PL) is considered as one of the safest target for diet-induced anti-obesity drug development. Orlistat is the only PL inhibitor approved for anti-obesity treatment till date. In the process of exploration of new PL inhibitors, we have screened culture filtrates of 70 endophytic fungi of medicinal plants using qualitative as well as quantitative in-vitro PL assays. The qualitative assays indicated potential PL inhibition in only three isolates, namely #57 TBBALM, #33 TBBALM and #1 CSSTOT. Only ethyl acetate extracts of the culture filtrates of these isolates exhibited the PL inhibition. #57 TBBLAM ethyl acetate extract of culture filtrate exhibited potential PL inhibition with an IC50 of 3.69 µg/ml which was comparable to the positive control, i.e. Orlistat exhibiting IC50 value of 2.73 µg/ml. Further molecular phylogenetic tools and morphological studies were used to identify the isolate #57 TBBALM as Penicillium species.

  5. Medicinal Plants and Their Inhibitory Activities against Pancreatic Lipase: A Review

    PubMed Central

    Seyedan, Atefehalsadat; Alshawsh, Mohammed Abdullah; Alshagga, Mustafa Ahmed; Koosha, Sanaz

    2015-01-01

    Obesity is recognized as a major life style disorder especially in developing countries and it is prevailing at an alarming speed in new world countries due to fast food intake, industrialization, and reduction of physical activity. Furthermore, it is associated with a vast number of chronic diseases and disabilities. To date, relatively effective drugs, from either natural or synthetic sources, are generally associated with serious side effects, often leading to cessation of clinical trials or even withdrawal from the market. In order to find new compounds which are more effective or with less adverse effects compared to orlistat, the drug that has been approved for obesity, new compounds isolated from natural products are being identified and screened for antiobesity effects, in particular, for their pancreatic lipase inhibitory effect. Pancreatic lipase inhibitory activity has been extensively used for the determination of potential efficacy of natural products as antiobesity agents. In attempts to identify natural products for overcoming obesity, more researches have been focused on the identification of newer pancreatic lipase inhibitors with less unpleasant adverse effects. In this review, we consider the potential role of plants that have been investigated for their pancreatic lipase inhibitory activity. PMID:26640503

  6. Hypocholesterolemic Effect and In Vitro Pancreatic Lipase Inhibitory Activity of an Opuntia ficus-indica Extract.

    PubMed

    Padilla-Camberos, Eduardo; Flores-Fernandez, Jose Miguel; Fernandez-Flores, Ofelia; Gutierrez-Mercado, Yanet; Carmona-de la Luz, Joel; Sandoval-Salas, Fabiola; Mendez-Carreto, Carlos; Allen, Kirk

    2015-01-01

    Cholesterol control is fundamental for prevention of cardiovascular disorders. In this work, the hypocholesterolemic activity of an aqueous Opuntia ficus-indica extract (AOE) was tested in triton-induced mice. The inhibitory activity on pancreatic lipase enzyme was evaluated in vitro by the same extract. Furthermore, polyphenol content of the extract was evaluated. Hypercholesterolemia was induced in three groups of mice by intraperitoneal administration of Triton WR-1339. After induction of hypercholesterolemia, the groups were treated with an AOE (500 mg/kg) and saline solution and the positive control group with orlistat, respectively. Cholesterol levels were measured 24 h later in peripheral blood. The levels of blood cholesterol after administration of AOE significantly decreased compared to negative control. The inhibitory activity of AOE on pancreatic lipase enzyme was evaluated at concentrations from 60 to 1000 μg/mL. The AOE inhibited the pancreatic lipase with an IC50 = 588.5 μg/mL. The AOE had a high content of polyphenolic compounds. These results show that AOE is able to prevent hypercholesterolemia by pancreatic lipase inhibition, in part due to its polyphenolic compounds.

  7. Hypocholesterolemic Effect and In Vitro Pancreatic Lipase Inhibitory Activity of an Opuntia ficus-indica Extract

    PubMed Central

    Flores-Fernandez, Jose Miguel; Fernandez-Flores, Ofelia; Gutierrez-Mercado, Yanet; Carmona-de la Luz, Joel; Sandoval-Salas, Fabiola; Mendez-Carreto, Carlos

    2015-01-01

    Cholesterol control is fundamental for prevention of cardiovascular disorders. In this work, the hypocholesterolemic activity of an aqueous Opuntia ficus-indica extract (AOE) was tested in triton-induced mice. The inhibitory activity on pancreatic lipase enzyme was evaluated in vitro by the same extract. Furthermore, polyphenol content of the extract was evaluated. Hypercholesterolemia was induced in three groups of mice by intraperitoneal administration of Triton WR-1339. After induction of hypercholesterolemia, the groups were treated with an AOE (500 mg/kg) and saline solution and the positive control group with orlistat, respectively. Cholesterol levels were measured 24 h later in peripheral blood. The levels of blood cholesterol after administration of AOE significantly decreased compared to negative control. The inhibitory activity of AOE on pancreatic lipase enzyme was evaluated at concentrations from 60 to 1000 μg/mL. The AOE inhibited the pancreatic lipase with an IC50 = 588.5 μg/mL. The AOE had a high content of polyphenolic compounds. These results show that AOE is able to prevent hypercholesterolemia by pancreatic lipase inhibition, in part due to its polyphenolic compounds. PMID:26078966

  8. The inhibitory effect of some drugs on Candida rugosa Lipase and Pancreatic Human Lipase: In vitro and in silico studies.

    PubMed

    Serseg, Talia; Benarous, Khedidja

    2018-03-18

    Side effects of some drugs may be useful in certain cases. In this work, we studied the inhibitory effects of some medications as: Folic Acid which is taken by pregnant women, Colchicine and Febuxostat which is used as treatment of gout disease. These cases are linked to obesity, where women (BMI ≥ 30) have twice higher odds of having an NTD-affected pregnancy than the normal weight women, and the Gout disease frequently occurs in combination of a Metabolic syndrome. The risk of gout increases with the increase of the mass index. In the first part of this study, we studied the inhibition activity of these medications on lipase activity of Candida rugosa in vitro, the results show that these drugs have an important inhibition activity with IC50 values 0.64 mg/ml for Folic acid and 0.66 mg/ml for Febuxostat. İn silico studies were aimed to determine the mechanism of inhibition and different interactions for two enzymes: Candida rugosa lipase and human pancreatic lipase. Autodock vina was used for molecular docking with 50 runs and 1000 obtained solutions. The results show competitive, Non-competitive and uncompetitive inhibition for folic acid, febuxostat and colchicine respectively for two enzymes with different repetition ratios of hydrogen bonds. The saved interactions were with His449 and Ser209 for the three molecules. These observations support a higher intake of dietary folate, and febuxostat for losing weight to decreased NTD risk and prevent hyperuricemia and recurrent gout attacks. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Pancreatic lipase and α-amylase inhibitory activities of plants used in Traditional Chinese Medicine (TCM).

    PubMed

    2016-07-07

    To find new, plant based drugs for the treatment of obesity and/or diabetes mellitus type 2 through the inhibition of essential digestive enzymes, in vitro tests were carried out on selected plants or fungi with weight-reducing, blood glucose-reducing or related potential, used in Traditional Chinese Medicine (TCM). Aqueous and methanolic extracts of 32 Chinese herbal medicines were assayed for their in vitro inhibitory activity against pancreatic lipase (PL) and α-amylase (PA). PL activity was measured by using an enzymatic in vitro assay based on the hydrolysis kinetics of an oleate ester of 4-methylumbelliferone. For the determination of α-amylase activity an enzyme assay based on the hydrolytic cleavage of a modified starch derivative was used. Our findings have shown that the methanolic extract of Lycopus lucidus Turcz. var. hirtus Regel (Lamiaceae) was a very effective PL inhibitor (IC50: 88.3±4.1 μg/mL). A high anti-amylase activity showed the methanolic extract of Trichosanthes kirilowii Maxim. (Curcurbitaceae, IC50: 248.8±67.3 μg/mL). This work provides a priority list of interesting plants for further study with respect to the treatment of obesity and associated metabolic diseases.

  10. Medicinal plant phytochemicals and their inhibitory activities against pancreatic lipase: molecular docking combined with molecular dynamics simulation approach.

    PubMed

    Ahmed, Bilal; Ali Ashfaq, Usman; Usman Mirza, Muhammad

    2018-05-01

    Obesity is the worst health risk worldwide, which is linked to a number of diseases. Pancreatic lipase is considered as an affective cause of obesity and can be a major target for controlling the obesity. The present study was designed to find out best phytochemicals against pancreatic lipase through molecular docking combined with molecular dynamics (MD) simulation. For this purpose, a total of 3770 phytochemicals were docked against pancreatic lipase and ranked them on the basis of binding affinity. Finally, 10 molecules (Kushenol K, Rosmarinic acid, Reserpic acid, Munjistin, Leachianone G, Cephamycin C, Arctigenin, 3-O-acetylpadmatin, Geniposide and Obtusin) were selected that showed strong bonding with the pancreatic lipase. MD simulations were performed on top five compounds using AMBER16. The simulated complexes revealed stability and ligands remained inside the binding pocket. This study concluded that these finalised molecules can be used as drug candidate to control obesity.

  11. Porcine Pancreatic Lipase Inhibitory Agent Isolated from Medicinal Herb and Inhibition Kinetics of Extracts from Eleusine indica (L.) Gaertner

    PubMed Central

    Ong, Siew Ling

    2016-01-01

    Eleusine indica (Linnaeus) Gaertner is a traditional herb known to be depurative, febrifuge, and diuretic and has been reported with the highest inhibitory activity against porcine pancreatic lipase (PPL) among thirty two plants screened in an earlier study. This study aims to isolate and identify the active components that may possess high potential as an antiobesity agent. Of the screened solvent fractions of E. indica, hexane fraction showed the highest inhibitory activity of 27.01 ± 5.68% at 100 μg/mL. Bioactivity-guided isolation afforded three compounds from the hexane fraction of E. indica, namely, β-sitosterol, stigmasterol, and lutein. The structures of these compounds were elucidated using spectral techniques. Lutein showed an outstanding inhibitory activity against PPL (55.98 ± 1.04%), with activity 60% higher than that of the reference drug Orlistat. The other compounds isolated and identified were β-sitosterol (2.99 ± 0.80%) and stigmasterol (2.68 ± 0.38%). The enzyme kinetics of E. indica crude methanolic extract on PPL showed mixed inhibition mechanism. PMID:27872792

  12. Porcine Pancreatic Lipase Inhibitory Agent Isolated from Medicinal Herb and Inhibition Kinetics of Extracts from Eleusine indica (L.) Gaertner.

    PubMed

    Ong, Siew Ling; Mah, Siau Hui; Lai, How Yee

    2016-01-01

    Eleusine indica (Linnaeus) Gaertner is a traditional herb known to be depurative, febrifuge, and diuretic and has been reported with the highest inhibitory activity against porcine pancreatic lipase (PPL) among thirty two plants screened in an earlier study. This study aims to isolate and identify the active components that may possess high potential as an antiobesity agent. Of the screened solvent fractions of E. indica , hexane fraction showed the highest inhibitory activity of 27.01 ± 5.68% at 100  μ g/mL. Bioactivity-guided isolation afforded three compounds from the hexane fraction of E. indica , namely,  β -sitosterol, stigmasterol, and lutein. The structures of these compounds were elucidated using spectral techniques. Lutein showed an outstanding inhibitory activity against PPL (55.98 ± 1.04%), with activity 60% higher than that of the reference drug Orlistat. The other compounds isolated and identified were  β -sitosterol (2.99 ± 0.80%) and stigmasterol (2.68 ± 0.38%). The enzyme kinetics of E. indica crude methanolic extract on PPL showed mixed inhibition mechanism.

  13. In vitro investigation of the potential health benefits of wild Mediterranean dietary plants as anti-obesity agents with α-amylase and pancreatic lipase inhibitory activities.

    PubMed

    Marrelli, Mariangela; Loizzo, Monica Rosa; Nicoletti, Marcello; Menichini, Francesco; Conforti, Filomena

    2014-08-01

    Inhibition of digestive enzymes is one of the most widely studied mechanisms used to determine the potential efficacy of natural products as anti-obesity agents. In vitro studies reported here were performed to evaluate the inhibitory activity of formulations of edible plants from Italy on amylase and lipase by monitoring the hydrolysis of nitrophenyl caprilate and the hydrolysis of glycoside bonds in digestible carbohydrate foods. The formulation obtained from Capparis sicula exhibited the strongest inhibitory effect on pancreatic lipase (IC50 = 0.53 mg mL(-1) ) while the Borago officinalis formulation exhibited the strongest inhibitory effect on α-amylase (IC50 = 31.61 µg mL(-1) ). In order to characterise the extracts, high-performance thin-layer chromatography analysis of the formulations was performed, revealing the predominance of (±)-catechin in Mentha aquatica formulation, rutin in C. sicula, and caffeic acid and chlorogenic acid in Echium vulgare. The results obtained indicated that the extracts of C. sicula and B. officinalis could be good candidates for further studies to isolate pancreatic lipase and α-amylase inhibitors, respectively. © 2013 Society of Chemical Industry.

  14. Phenolic antioxidants in some Vigna species of legumes and their distinct inhibitory effects on α-glucosidase and pancreatic lipase activities.

    PubMed

    Sreerama, Yadahally N; Takahashi, Yoko; Yamaki, Kohji

    2012-09-01

    Phenolic extracts of 4 Vigna species of legumes (mung bean, moth bean, and black and red varieties of adzuki beans) were evaluated for phenolic contents, antioxidant activities, and inhibitory properties against α-glucosidase and pancreatic lipase. Results showed that adzuki bean varieties contain higher phenolic indexes than mung bean and moth beans. Adzuki bean (black) variety was found to be the most active 2,2'-diphenyl-1-picrylhydrazyl and superoxide anion scavenger. However, the hydrogen peroxide scavenging and metal chelating abilities were significantly higher in adzuki bean (red) variety. Mung bean exhibited least antioxidant activities in all the methods tested. Phenolic extracts from these legumes also showed distinct variations in the inhibition of enzymes associated with hyperglycemia and hyperlipidemia. Inhibitory activities of all the extracts against lipase were found to be more potent than α-glucosidase. Although, α-glucosidase inhibitory activity was superior in the black variety of adzuki bean (IC(50,) 26.28 mg/mL), both adzuki bean varieties (black and red) along with moth bean showed strong inhibitory activities on lipase with no significant difference in their IC(50) values (7.32 to 9.85 mg/mL). These results suggest that Vigna species of legumes are potential source of antioxidant phenolics and also great sources of strong natural inhibitors for α-glucosidase and lipase activities. This information may help for effective utilization of these legumes as functional food ingredients for promoting health. Practical Application:  Vigna species of legumes are good sources of phenolic antioxidants and strong natural inhibitors of enzymes associated with diabetes and obesity. Therefore, utilization of these legumes in the development of functional foods with increased therapeutic value would be a significant step toward health promotion and wellness. © 2012 Institute of Food Technologists®

  15. Impact of roasting on the flavan-3-ol composition, sensory-related chemistry, and in vitro pancreatic lipase inhibitory activity of cocoa beans.

    PubMed

    Stanley, Todd H; Van Buiten, Charlene B; Baker, Scott A; Elias, Ryan J; Anantheswaran, Ramaswamy C; Lambert, Joshua D

    2018-07-30

    Roasting is an important cocoa processing step, but has been reported to reduce the polyphenol content in the beans. We investigated the impact of whole-bean roasting on the polyphenol content, aroma-related chemistry, and in vitro pancreatic lipase (PL) inhibitory activity of cocoa under a range of roasting conditions. Total phenolics, (-)-epicatechin, and proanthocyanidin (PAC) dimer - pentamer content was reduced by roasting. By contrast, roasting at 150 °C or greater increased the levels of catechin and PAC hexamers and heptamers. These compounds have greater PL inhibitory potency. Consistent with these changes in PAC composition and this previous data, we found that roasting at 170 °C time-dependently increased PL inhibitory activity. Cocoa aroma-related compounds increased with roasting above 100 °C, whereas deleterious sensory-related compounds formed at more severe temperatures. Our results indicate that cocoa roasting can be optimized to increase the content of larger PACs and anti-PL activity, while maintaining a favorable aroma profile. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Inhibition of pancreatic lipase and amylase by extracts of different spices and plants.

    PubMed

    Sellami, Mohamed; Louati, Hanen; Kamoun, Jannet; Kchaou, Ali; Damak, Mohamed; Gargouri, Youssef

    2017-05-01

    The aim of this study is to search new anti-obesity and anti-diabetic agents from plant and spices crude extracts as alternative to synthetic drugs. The inhibitory effect of 72 extracts was evaluated, in vitro, on lipase and amylase activities. Aqueous extracts of cinnamon and black tea exhibited an appreciable inhibitory effect on pancreatic amylase with IC 50 values of 18 and 87 μg, respectively. Aqueous extracts of cinnamon and mint showed strong inhibitory effects against pancreatic lipase with IC 50 of 45 and 62 μg, respectively. The presence of bile salts and colipase or an excess of interface failed to restore the lipase activity. Therefore, the inhibition of pancreatic lipase, by extracts of spices and plants, belongs to an irreversible inhibition. Crude extract of cinnamon showed the strongest anti-lipase and anti-amylase activities which offer a prospective therapeutic approach for the management of diabetes and obesity.

  17. Chemical composition and inhibitory activities on dipeptidyl peptidase IV and pancreatic lipase of two underutilized species from the Brazilian Savannah: Oxalis cordata A.St.-Hil. and Xylopia aromatica (Lam.) Mart.

    PubMed

    Oliveira, Verena B; Araújo, Raquel L B; Eidenberger, Thomas; Brandão, Maria G L

    2018-03-01

    Brazil has the greatest vegetal biodiversity in the world, but products derived from native species are not optimally utilized. Oxalis cordata and Xylopia aromatica are two underutilized species whose leaves and fruits, respectively, have been used as food in the 19th century. In this study, we used chemical and in vitro assays to evaluate the potential of these species as functional foods. The inhibitory activity on pancreatic lipase and DPP-IV were evaluated using the crude extracts and fractions ethyl acetate, butanol and water of these two species. For polyphenols determination, samples were prepared with different solvents and these were analysed by chromatographic and spectroscopic methods. Finally, fatty acids profile was determinated by gas chromatography. The crude extract (IC 50 =0.84mg/ml), ethyl acetate extract (IC 50 =0.88mg/ml) an aqueous fraction (IC 50 =0.63mg/ml) of C. cordata were inhibitory on pancreatic lipase but inactive against dipeptidyl peptidase IV (DPP-IV). Extracts from X. aromatica were inactive against the lipase pancreatic enzyme, but a butanolic fraction inhibited DPP-IV (IC 50 =0.71±0.05mg/ml). The phenolic acids orientin/isorientin, chlorogenic acid (0.32g/100g) and the flavonoid derivatives rutin (0.27g/100g), quercetin and luteolin were observed in all products. Additionally, fatty acid quantification showed that oleic (7.5g/100g) and linoleic acid (6.5g/100g) were predominant in X. aromatica fruit. This study confirms the potential for the use of both plants as functional foods due to their nutritional value, biological activity and important phytochemical content. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Bound Phenolics of Quinoa Seeds Released by Acid, Alkaline, and Enzymatic Treatments and Their Antioxidant and α-Glucosidase and Pancreatic Lipase Inhibitory Effects.

    PubMed

    Tang, Yao; Zhang, Bing; Li, Xihong; Chen, Peter X; Zhang, Hua; Liu, Ronghua; Tsao, Rong

    2016-03-02

    Unextractable phenolics from plant foods and their role in health benefits have become increasingly important. Meal residues of three quinoa seeds free of fat and extractable phenolics were subjected to acid, alkaline, and enzymatic hydrolyses. The total and individual phenolic compounds released were analyzed, and 19 phenolics, predominantly phenolic acids and several flavonoids, were identified. The concentration of bound phenolics was highest in black quinoa followed by red and white, regardless of the hydrolysis method. Higher phenolic contents also showed stronger antioxidant activities and inhibition of α-glucosidase and pancreatic lipase activities. Carbohydrases, that is, pectinase, xylanase and feruloyl esterase, which effectively liberated bound phenolics are known to be secreted by colonic bacteria, suggesting potential antioxidant and anti-inflammatory effects by these compounds in the large intestine during colonic fermentation. These results can also be applied to treat foods high in bound phenolics to enhance bioaccessibility.

  19. Sempervivum davisii: phytochemical composition, antioxidant and lipase-inhibitory activities.

    PubMed

    Uzun, Yusuf; Dalar, Abdullah; Konczak, Izabela

    2017-12-01

    Sempervivum davisii Muirhead (Crassulaceae) is a traditional medicinal herb from Eastern Anatolia. To date the composition of phytochemicals and physiological properties of this herb were not subjected to any research. This study identifies compounds in S. davisii hydrophilic extracts and evaluates their potential biological properties. Ethanol-based lyophilized extracts were obtained from aerial parts of plant (10 g of ground dry plant material in 200 mL of acidified aqueous ethanol, shaken for 2 h at 22 °C with supernatant collected and freeze-dried under vacuum). Phytochemical composition was investigated by liquid chromatography mass spectrometry (LC-MS/MS, phenolics) and gas chromatography mass spectrometry (GC-MS, volatiles). Phenolic compounds were quantified by high-performance liquid chromatography (HPLC) and the Folin-Ciocalteu assay. Subsequently, antioxidant capacity [ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC) assays] and enzyme inhibitory properties (isolated porcine pancreatic lipase) of the extracts were determined. Polyphenolic compounds were the main constituents of lyophilized extracts, among which kaempferol glycosides and quercetin hexoside dominated. The extracts exhibited potent antioxidant (FRAP values of 1925.2-5973.3 μM Fe 2+ /g DW; ORAC values of 1858.5-4208.7 μM Trolox Eq./g DW) and moderate lipase inhibitory (IC 50 : 11.6-2.96 mg/mL) activities. Volatile compounds (nonanal, dehydroxylinalool oxide isomers, 2-decenal, 2-undecenal, 2,6-di-tetr-butylphenol) were also found. Phenolic compounds with the dominating kaempferol and quercetin derivatives are the sources of potent antioxidant properties of S. davisii hydrophilic extracts. The extracts exhibit moderate inhibitory properties towards isolated pancreatic lipase.

  20. Lipase or amylase for the diagnosis of acute pancreatitis?

    PubMed

    Ismail, Ola Z; Bhayana, Vipin

    2017-12-01

    Acute pancreatitis is a rapid onset of inflammation of the pancreas causing mild to severe life threatening conditions [1, 2]. In Canada, acute pancreatitis is the 5th most expensive digestive disease in Canada with a considerable economic burden on the health care system [3]. The diagnosis of acute pancreatitis is usually based on the presence of abdominal pain and elevated levels of serum amylase and/or lipase. Many health care centers use either serum amylase, lipase or both to diagnose acute pancreatitis without considering which one could provide a better diagnostic accuracy. The aim of this review is to investigate whether serum lipase alone is a sufficient biomarker for the diagnosis of acute pancreatitis. We have examined various studies looking at the utilization, sensitivity, specificity and cost associated savings of lipase and amylase in the diagnosis of acute pancreatitis. When comparing different studies, serum lipase offers a higher sensitivity than serum amylase in diagnosing acute pancreatitis. Lipase also offers a larger diagnostic window than amylase since it is elevated for a longer time, thus allowing it to be a useful diagnostic biomarker in early and late stages of acute pancreatitis. Several recent evidence-based guidelines recommend the use of lipase over amylase. Nevertheless, both lipase and amylase alone lack the ability to determine the severity and etiology of acute pancreatitis. The co-ordering of both tests has shown little to no increase in the diagnostic sensitivity and specificity. Thus, unnecessary testing and laboratory expenditures can be reduced by testing lipase alone. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  1. Lipolysis of Visceral Adipocyte Triglyceride by Pancreatic Lipases Converts Mild Acute Pancreatitis to Severe Pancreatitis Independent of Necrosis and Inflammation

    PubMed Central

    Patel, Krutika; Trivedi, Ram N.; Durgampudi, Chandra; Noel, Pawan; Cline, Rachel A.; DeLany, James P.; Navina, Sarah; Singh, Vijay P.

    2016-01-01

    Visceral fat necrosis has been associated with severe acute pancreatitis (SAP) for over 100 years; however, its pathogenesis and role in SAP outcomes are poorly understood. Based on recent work suggesting that pancreatic fat lipolysis plays an important role in SAP, we evaluated the role of pancreatic lipases in SAP-associated visceral fat necrosis, the inflammatory response, local injury, and outcomes of acute pancreatitis (AP). For this, cerulein pancreatitis was induced in lean and obese mice, alone or with the lipase inhibitor orlistat and parameters of AP induction (serum amylase and lipase), fat necrosis, pancreatic necrosis, and multisystem organ failure, and inflammatory response were assessed. Pancreatic lipases were measured in fat necrosis and were overexpressed in 3T3-L1 cells. We noted obesity to convert mild cerulein AP to SAP with greater cytokines, unsaturated fatty acids (UFAs), and multisystem organ failure, and 100% mortality without affecting AP induction or pancreatic necrosis. Increased pancreatic lipase amounts and activity were noted in the extensive visceral fat necrosis of dying obese mice. Lipase inhibition reduced fat necrosis, UFAs, organ failure, and mortality but not the parameters of AP induction. Pancreatic lipase expression increased lipolysis in 3T3-L1 cells. We conclude that UFAs generated via lipolysis of visceral fat by pancreatic lipases convert mild AP to SAP independent of pancreatic necrosis and the inflammatory response. PMID:25579844

  2. Crude Aloe vera Gel Shows Antioxidant Propensities and Inhibits Pancreatic Lipase and Glucose Movement In Vitro

    PubMed Central

    Taukoorah, Urmeela; Mahomoodally, M. Fawzi

    2016-01-01

    Aloe vera gel (AVG) is traditionally used in the management of diabetes, obesity, and infectious diseases. The present study aimed to investigate the inhibitory potential of AVG against α-amylase, α-glucosidase, and pancreatic lipase activity in vitro. Enzyme kinetic studies using Michaelis-Menten (K m) and Lineweaver-Burk equations were used to establish the type of inhibition. The antioxidant capacity of AVG was evaluated for its ferric reducing power, 2-diphenyl-2-picrylhydrazyl hydrate scavenging ability, nitric oxide scavenging power, and xanthine oxidase inhibitory activity. The glucose entrapment ability, antimicrobial activity, and total phenolic, flavonoid, tannin, and anthocyanin content were also determined. AVG showed a significantly higher percentage inhibition (85.56 ± 0.91) of pancreatic lipase compared to Orlistat. AVG was found to increase the Michaelis-Menten constant and decreased the maximal velocity (V max) of lipase, indicating mixed inhibition. AVG considerably inhibits glucose movement across dialysis tubes and was comparable to Arabic gum. AVG was ineffective against the tested microorganisms. Total phenolic and flavonoid contents were 66.06 ± 1.14 (GAE)/mg and 60.95 ± 0.97 (RE)/mg, respectively. AVG also showed interesting antioxidant properties. The biological activity observed in this study tends to validate some of the traditional claims of AVG as a functional food. PMID:26880905

  3. Human pancreatic lipase-related protein 2 is a galactolipase.

    PubMed

    Sias, Barbara; Ferrato, Francine; Grandval, Philippe; Lafont, Dominique; Boullanger, Paul; De Caro, Alain; Leboeuf, Bernard; Verger, Robert; Carrière, Frédéric

    2004-08-10

    Human pancreatic lipase-related protein 2 (HPLRP2) was found to be expressed in the pancreas, but its biochemical properties were not investigated in detail. A recombinant HPLRP2 was produced in insect cells and the yeast Pichia pastoris and purified by cation exchange chromatography. Its substrate specificity was investigated using pH-stat and monomolecular film techniques and various lipid substrates (triglycerides, diglycerides, phospholipids, and galactolipids). Lipase activity of HPLRP2 on trioctanoin was inhibited by bile salts and poorly restored by adding colipase. In vivo, HPLRP2 therefore seems unlikely to show any lipase activity on dietary fat. In human pancreatic lipase (HPL), residues R256, D257, Y267, and K268 are involved in the stabilization of the open conformation of the lid domain, which interacts with colipase. These residues are not conserved in HPLRP2. When the corresponding mutations (R256G, D257G, Y267F, and K268E) are introduced into HPL, the effects of colipase are drastically reduced in the presence of bile salts. This may explain why colipase has such weak effects on HPLRP2. HPLRP2 displayed a very low level of activity on phospholipid micelles and monomolecular films. Its activity on monogalactosyldiglyceride monomolecular film, which was much higher, was similar to the activity of guinea pig pancreatic lipase related-protein 2, which shows the highest galactolipase activity ever measured. The physiological role of HPLRP2 suggested by the present results is the digestion of galactolipids, the most abundant lipids occurring in plant cells, and therefore, in the vegetables that are part of the human diet.

  4. Pancreatic adenocarcinoma, chronic pancreatitis, and MODY-8 diabetes: is bile salt-dependent lipase (or carboxyl ester lipase) at the crossroads of pancreatic pathologies?

    PubMed

    Lombardo, Dominique; Silvy, Françoise; Crenon, Isabelle; Martinez, Emmanuelle; Collignon, Aurélie; Beraud, Evelyne; Mas, Eric

    2018-02-23

    Pancreatic adenocarcinomas and diabetes mellitus are responsible for the deaths of around two million people each year worldwide. Patients with chronic pancreatitis do not die directly of this disease, except where the pathology is hereditary. Much current literature supports the involvement of bile salt-dependent lipase (BSDL), also known as carboxyl ester lipase (CEL), in the pathophysiology of these pancreatic diseases. The purpose of this review is to shed light on connections between chronic pancreatitis, diabetes, and pancreatic adenocarcinomas by gaining an insight into BSDL and its variants. This enzyme is normally secreted by the exocrine pancreas, and is diverted within the intestinal lumen to participate in the hydrolysis of dietary lipids. However, BSDL is also expressed by other cells and tissues, where it participates in lipid homeostasis. Variants of BSDL resulting from germline and/or somatic mutations (nucleotide insertion/deletion or nonallelic homologous recombination) are expressed in the pancreas of patients with pancreatic pathologies such as chronic pancreatitis, MODY-8, and pancreatic adenocarcinomas. We discuss the possible link between the expression of BSDL variants and these dramatic pancreatic pathologies, putting forward the suggestion that BSDL and its variants are implicated in the cell lipid metabolism/reprogramming that leads to the dyslipidemia observed in chronic pancreatitis, MODY-8, and pancreatic adenocarcinomas. We also propose potential strategies for translation to therapeutic applications.

  5. Pancreatic Lipase Immunoreactivity in Serum of Dogs with Diabetic Ketoacidosis.

    PubMed

    Bolton, T A; Cook, A; Steiner, J M; Fosgate, G T

    2016-07-01

    Diabetic ketoacidosis (DKA) is a relatively common endocrine disorder in dogs and is routinely associated with concurrent pancreatic injury. The aims of this study were to determine the prevalence of pancreatic injury in dogs with DKA based on measurement of pancreatic lipase immunoreactivity in serum (PLI); compare demographic, clinicopathologic, and ultrasonographic findings in dogs with and without evidence of concurrent pancreatic injury; determine the impact of pancreatic injury on duration of hospitalization and short-term outcome. One hundred and nineteen dogs with DKA with or without concurrent pancreatic injury. Retrospective study. Dogs with DKA were divided into three groups on the basis of PLI results: positive for pancreatic injury (PLIpos ), negative for pancreatic injury (PLIneg ), and not tested (PLIna ). Demographics, clinicopathologic test results, findings on abdominal ultrasonography (AUS), duration of hospitalization, and short-term outcome were compared between the three groups. Based on serum PLI activity, 45 dogs (73%) with DKA had evidence of concurrent pancreatic injury. Median total carbon dioxide was significantly lower in the PLIpos dogs compared to the PLIneg dogs. There was fair agreement (κ = 0.26) between serum PLI activity and AUS. Evidence of pancreatic injury was not associated with significantly longer periods of hospitalization (PLIpos median 6 days, range 4-7 days, PLIneg median 4 days, range 3-6 days) and did not influence short-term outcome (PLIpos failure to survive to discharge 11/45, 24%, PLIneg failure to survive to discharge 2/17, 12%). Concurrent pancreatic injury is common in dogs with DKA, but did not affect prognosis in this population of dogs. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  6. In vitro lipolysis by human pancreatic lipase is specifically abolished by its inactive forms.

    PubMed

    Miled, N; Berti-Dupuis, L; Riviere, M; Carrière, F; Verger, R

    2003-02-21

    In human adults, the enzymatic hydrolysis of dietary fat along the digestive tract is sequentially catalyzed by two main enzymes, human gastric lipase (HGL) and human pancreatic lipase (HPL). Both a chemically inhibited form of HPL as well as an inactive HPL mutant with a glycine residue substituted for its catalytic serine were found to be strong inactivators of HPL activity. In the presence of bile salts, this inhibition was clearly due to competition for colipase. We established that the chemically inhibited HPL, probably in its open conformation, had a much greater affinity for colipase than the closed native form of HPL. These inhibitory effects are quite substantial, because a 0.2-M excess of the chemically inhibited HPL form relative to HPL reduced the catalytic lipolytic activity by 50% in the presence of an equimolar amount of colipase.

  7. Characterization of pancreatic lipase-related protein 2 isolated from human pancreatic juice.

    PubMed

    De Caro, Josiane; Sias, Barbara; Grandval, Philippe; Ferrato, Francine; Halimi, Hubert; Carrière, Frédéric; De Caro, Alain

    2004-09-01

    Human pancreatic lipase-related protein 2 (HPLRP2) was identified for the first time in pancreatic juice using specific anti-peptide antibodies and purified to homogeneity. Antibodies were raised in the rabbit using a synthetic peptide from the HPLRP2 protein sequence deduced from cDNA. Western blotting analysis showed that these antibodies did not react with classical human pancreatic lipase (HPL) or human pancreatic lipase-related protein 1 (HPLRP1) but cross-reacted with native rat PLRP2 (RPLRP2), as well as with recombinant rat and guinea-pig PLRP2 (GPLRP2). Immunoaffinity chromatography was performed on immobilized anti-recombinant HPLRP2 polyclonal antibodies to purify native HPLRP2 after conventional chromatographic steps including gel filtration and chromatrography on an anion-exchanger. The substrate specificity of HPLRP2 was investigated using various triglycerides, phospholipids and galactolipids as substrates. The lipase activity on triglycerides was inhibited by bile salts and weakly restored by colipase. The phospholipase activity of HPLRP2 on phospholipid micelles was very low. A significant level of galactolipase activity was measured using monogalactosyldiglyceride monomolecular films. These data suggest that the main physiological function of HPLRP2 is the hydrolysis of galactolipids, which are the main lipids present in vegetable food.

  8. In vitro Inhibition of Pancreatic Lipase by Polyphenols:
A Kinetic, Fluorescence Spectroscopy and Molecular Docking Study

    PubMed Central

    2017-01-01

    Summary The inhibitory activity and binding characteristics of caffeic acid, p-coumaric acid, quercetin and capsaicin, four phenolic compounds found in hot pepper, against porcine pancreatic lipase activity were studied and compared to hot pepper extract. Quercetin was the strongest inhibitor (IC50=(6.1±2.4) µM), followed by p-coumaric acid ((170.2±20.6) µM) and caffeic acid ((401.5±32.1) µM), while capsaicin and a hot pepper extract had very low inhibitory activity. All polyphenolic compounds showed a mixed-type inhibition. Fluorescence spectroscopy studies showed that polyphenolic compounds had the ability to quench the intrinsic fluorescence of pancreatic lipase by a static mechanism. The sequence of Stern-Volmer constant was quercetin, followed by caffeic and p-coumaric acids. Molecular docking studies showed that caffeic acid, quercetin and p-coumaric acid bound near the active site, while capsaicin bound far away from the active site. Hydrogen bonds and π-stacking hydrophobic interactions are the main pancreatic lipase-polyphenolic compound interactions observed. PMID:29540986

  9. Rat lingual lipase: partial purification, hydrolytic properties, and comparison with pancreatic lipase.

    PubMed

    Roberts, I M; Montgomery, R K; Carey, M C

    1984-10-01

    We have partially purified lingual lipase from the serous glands of rat tongue. With a combination of Triton X-100 extraction or Triton X-114 phase-separation techniques, Bio-Bead SM-2 treatment, dialysis, and gel filtration on Sephadex G-200 or Sephacryl S-300, we obtained a sparingly soluble lipid-free protein demonstrating hydrolytic activity against triglycerides and negligible phospholipase or cholesteryl esterase activities. Compared with homogenate, specific activities of the enzyme were enriched 3- to 5-fold prior to gel filtration and 10-fold after gel filtration. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration under denaturing conditions (6 M guanidine X HCl or 0.1% sodium dodecyl sulfate) revealed one major glycoprotein band with Mr approximately 50,000. Gel filtration of the active enzyme in 0.1% Triton X-100 gave an Mr approximately 270,000-300,000, suggesting extensive self-aggregation. With both tributyrin and triolein, the pH optimum of the purified enzyme was 4.0 and activity extended from pH 2.0 to 8.0. In contrast to purified human pancreatic lipase, lingual lipase hydrolyzed triglyceride emulsions and mixed micelles stabilized with both short-chain (dihexanoyl) and long-chain (egg) lecithin and were inhibited only slightly (18-25%) by micellar concentrations of two common bile salts, taurodeoxycholate and taurocholate. Our results suggest that the hydrolysis of dietary fat by lingual lipase may extend from the pharynx through the esophagus and stomach and into the upper small intestine.

  10. Pancreatic lipase-related protein 2 digests fats in human milk and formula in concert with gastric lipase and carboxyl ester lipase

    PubMed Central

    Johnson, Karin; Ross, Leah; Miller, Rita; Xiao, Xunjun; Lowe, Mark E.

    2013-01-01

    INTRODUCTION Dietary fats must be digested into fatty acids and monoacylglycerols prior to absorption. In adults, colipase-dependent pancreatic triglyceride lipase (PTL) contributes significantly to fat digestion. In newborn rodents and humans, the pancreas expresses low levels of PTL. In rodents, a homologue of PTL, pancreatic lipase related protein 2 (PLRP2) and carboxyl ester lipase (CEL) compensate for the lack of PTL. In human newborns, the role for PLRP2 in dietary fat digestion is unclear. To clarify the potential of human PLRP2 to influence dietary fat digestion in newborns, we determined PLRP2 activity against human milk and infant formula. METHODS The activity of purified recombinant PLRP2, gastric lipase and CEL against fats in human milk and formula was measured with each lipase alone and in combination with a standard pH-stat assay. RESULTS Colipase added to human milk stimulated fat digestion. PLRP2 and CEL had activity against human milk and formula. Pre-digestion with gastric lipase increased PLRP2 activity against both substrates. Together, CEL and PLRP2 activity was additive with formula and synergistic with human milk. CONCLUSIONS PLRP2 can digest fats in human milk and formula. PLRP2 acts in concert with CEL and gastric lipase to digest fats in human milk in vitro. PMID:23732775

  11. Canine pancreatic lipase immunoreactivity concentrations associated with intervertebral disc disease in 84 dogs.

    PubMed

    Schueler, R O; White, G; Schueler, R L; Steiner, J M; Wassef, A

    2018-05-01

    To determine the differences in serum canine pancreatic lipase immunoreactivity between dogs with intervertebral disc herniation and healthy control dogs. Eighty-four client-owned dogs with intervertebral disc herniation, diagnosed by neurologic examination and imaging, and 18 healthy control dogs. Samples of whole blood were collected within 90 minutes of admission. Serum canine pancreatic lipase immunoreactivity concentrations were measured by a commercial immunoassay and evaluated for association with intervertebral disc herniation, signalment, neurolocalisation and the preadmission administration of glucocorticosteriods or non-steroidal anti-inflammatory drugs. Serum canine pancreatic lipase immunoreactivity concentrations were statistically increased in dogs with intervertebral disc herniation (P<0·01, n=38). A subgroup of dogs (19/38) with elevated canine pancreatic lipase immunoreactivity concentrations was re-evaluated between 2 and 4 weeks later, and 15 had resolution of clinical signs and values less than 200 μg/L. Serum canine pancreatic lipase immunoreactivity concentrations were not significantly correlated with clinical gastrointestinal disease, neurolocalisation or the preadmission administration of corticosteroids or non-steroidal anti-inflammatory drugs. These results suggest that serum canine pancreatic lipase immunoreactivity concentrations are significantly elevated in dogs with intervertebral disc herniation. © 2018 British Small Animal Veterinary Association.

  12. In Silico Identification of Potent Pancreatic Triacylglycerol Lipase Inhibitors from Traditional Chinese Medicine

    PubMed Central

    Chen, Kuan-Yu; Chang, Su-Sen; Chen, Calvin Yu-Chian

    2012-01-01

    Pancreatic triacylglycerol lipase (PNLIP) are primary lipases that are critical for triacylglyceride digestion in human. Since reduced metabolism of triacylglyceride might be a plausible concept for weight loss, we screened for potential PNLIP inhibitors from traditional Chinese medicine (TCM) with the aim to identify weight loss candidate compounds. TCM candidates Aurantiamide, Cnidiadin, and 2-hexadecenoic acid exhibited higher Dock Scores than the commercial drug Orlistat, and were also predicted to have inhibitory characteristics against PNLIP using constructed MLR (R2 = 0.8664) and SVM (R2 = 0.9030) models. Molecular dynamics indicated that the TCM-PNLIP complexes formed were stable. We identified that the PNLIP binding site has several residues that can serve as anchors, and a hydrophobic corridor that provides additional stability to the complex. Aurantiamide, Cnidiadin, and 2-hexadecenoic acid all have features that correspond to these binding site features, indicating their potential as candidates for PNLIP inhibitors. The information presented in this study may provide helpful insights to designing novel weight-control drugs. PMID:22970152

  13. In silico identification of potent pancreatic triacylglycerol lipase inhibitors from traditional Chinese medicine.

    PubMed

    Chen, Kuan-Yu; Chang, Su-Sen; Chen, Calvin Yu-Chian

    2012-01-01

    Pancreatic triacylglycerol lipase (PNLIP) are primary lipases that are critical for triacylglyceride digestion in human. Since reduced metabolism of triacylglyceride might be a plausible concept for weight loss, we screened for potential PNLIP inhibitors from traditional Chinese medicine (TCM) with the aim to identify weight loss candidate compounds. TCM candidates Aurantiamide, Cnidiadin, and 2-hexadecenoic acid exhibited higher Dock Scores than the commercial drug Orlistat, and were also predicted to have inhibitory characteristics against PNLIP using constructed MLR (R(2) = 0.8664) and SVM (R(2) = 0.9030) models. Molecular dynamics indicated that the TCM-PNLIP complexes formed were stable. We identified that the PNLIP binding site has several residues that can serve as anchors, and a hydrophobic corridor that provides additional stability to the complex. Aurantiamide, Cnidiadin, and 2-hexadecenoic acid all have features that correspond to these binding site features, indicating their potential as candidates for PNLIP inhibitors. The information presented in this study may provide helpful insights to designing novel weight-control drugs.

  14. Serial measurement of pancreatic lipase immunoreactivity concentration in dogs with immune-mediated disease treated with prednisolone.

    PubMed

    Ohta, H; Morita, T; Yokoyama, N; Osuga, T; Sasaki, N; Morishita, K; Nakamura, K; Takiguchi, M

    2017-06-01

    In this pilot study, serum canine pancreatic lipase immunoreactivity was measured repeatedly in dogs with various immune-mediated diseases that were treated with immunosuppressive doses of prednisolone. Ten client-owned dogs with newly diagnosed immune-mediated disease that had normal canine pancreatic lipase immunoreactivity concentrations (≤200 µg/l) were treated with 2 to 2.2 mg/kg prednisolone orally once daily as the initial treatment. Serum samples were obtained from each of the dogs prior to treatment and at 1- to 4-week intervals during immunosuppressive treatment. The highest canine pancreatic lipase immunoreactivity concentration detected during immunosuppressive treatment was defined as the peak canine pancreatic lipase immunoreactivity. Peak canine pancreatic lipase immunoreactivity concentrations were classified as normal in two dogs, questionable (201 to 399 µg/l) in three dogs, and abnormal (≥400 µg/l) in five dogs. Peak canine pancreatic lipase immunoreactivity concentrations were significantly higher than baseline canine pancreatic lipase immunoreactivity concentrations but there was no evidence of clinical pancreatitis. It remains unclear whether the five of 10 dogs with elevated canine pancreatic lipase immunoreactivity during prednisone treatment had subclinical pancreatitis or whether the abnormal results were a consequence of prednisolone administration. © 2017 British Small Animal Veterinary Association.

  15. Development of an indirect method for measuring porcine pancreatic lipase in human duodenal fluid.

    PubMed

    Tuvignon, N; Abousalham, A; Tocques, F; De Caro, J; De Caro, A; Laugier, R; Carrière, F

    2008-12-15

    Patients with exocrine pancreatic insufficiency are usually treated with porcine pancreatic enzymes but the bioavailability of these enzymes in the gut remains a matter of discussion. In order to determine the duodenal availability of porcine pancreatic lipase (PPL) present in pancreatic extracts (PE) taken orally, we developed a method for quantifying PPL in samples containing both PPL and human pancreatic lipase (HPL). Total pancreatic lipase activity measurements using the pH-stat technique and tributyrin as substrate were combined with an HPL-specific ELISA. Based on the known specific activity of the purified HPL, its activity was deduced from the ELISA measurements, and the PPL activity was obtained by subtracting the HPL activity from the total pancreatic lipase activity. This assay was established and validated using various samples containing pure PPL and recombinant HPL or PE, mixed or not with human duodenal juice. Samples collected in vivo from patients treated with PE were also tested. It was found that PPL did not affect the HPL ELISA, and the indirect PPL assay gave a measurement accuracy of 6.6% with the samples containing pure PPL and 10% with those containing PE. This assay was also used successfully to discriminate between PPL and the endogenous HPL present in the duodenal contents of patients with severe pancreatic insufficiency treated with PE. This method might provide a useful means of assessing the availability of PEs at their site of action, in the absence of a PPL-specific ELISA.

  16. Kinetic properties of dromedary pancreatic lipase: a comparative study on emulsified and monomolecular substrate.

    PubMed

    Jemel, Ikram; Fendri, Ahmed; Gargouri, Youssef; Bezzine, Sofiane

    2009-05-01

    Using the classical emulsified system and the monomolecular film technique, we compared several interfacial properties of dromedary pancreatic lipase (DrPL) with those of a mammal (human) and an avian (turkey) model. Like turkey pancreatic lipase (TPL) and unlike human pancreatic lipase (HPL), in the absence of colipase and bile salts, using tributyrin emulsion or monomolecular films of dicaprin at low surface pressure, DrPL hydrolyses pure tributyrin emulsion, as well as dicaprin films maintained at low surface pressures. DrPL was also able to hydrolyse triolein emulsion in the absence of any additive and despite the accumulation of long-chain free fatty acids at the interface. The difference of behaviours between the two mammal pancreatic lipases (DrPL and HPL) can be explained by the penetration capacity of each enzyme. DrPL presents a critical surface pressure value (21 m Nm(-1)) that is more important than this of HPL. Subsequently, the dromedary pancreatic lipase interacts efficiently with interfaces and it is not denaturated at high interfacial energy. A kinetic study on the surface pressure dependency, stereospecificity and regioselectivity of DrPL was performed using optically pure stereoisomers of either three dicaprin isomers containing a single hydrolysable decanoyl ester bond that were spread as monomolecular films at the air/water interface. Interestingly, in comparison with all the previously studied mammal pancreatic lipases, DrPL presents the highest preference for adjacent ester groups of dicaprin isomers (1,2-sn-dicaprin and 2,3-sn-dicaprin) at high surface pressure. Furthermore, DrPL forms a pancreatic lipase subgroup in which the stereopreference switches from sn-3 position to the sn-1 position when increasing the surface pressure.

  17. Molecular Interactions between (−)-Epigallocatechin Gallate Analogs and Pancreatic Lipase

    PubMed Central

    Wang, Shihui; Sun, Zeya; Dong, Shengzhao; Liu, Yang; Liu, Yun

    2014-01-01

    The molecular interactions between pancreatic lipase (PL) and four tea polyphenols (EGCG analogs), like (−)-epigallocatechin gallate (EGCG), (−)-gallocatechin gallate (GCG), (−)-epicatechin gallate (ECG), and (−)-epigallocatechin (EC), were studied from PL activity, conformation, kinetics and thermodynamics. It was observed that EGCG analogs inhibited PL activity, and their inhibitory rates decreased by the order of EGCG>GCG>ECG>EC. PL activity at first decreased rapidly and then slowly with the increase of EGCG analogs concentrations. α-Helix content of PL secondary structure decreased dependent on EGCG analogs concentration by the order of EGCG>GCG>ECG>EC. EGCG, ECG, and EC could quench PL fluorescence both dynamically and statically, while GCG only quenched statically. EGCG analogs would induce PL self-assembly into complexes and the hydrodynamic radii of the complexes possessed a close relationship with the inhibitory rates. Kinetics analysis showed that EGCG analogs non-competitively inhibited PL activity and did not bind to PL catalytic site. DSC measurement revealed that EGCG analogs decreased the transition midpoint temperature of PL enzyme, suggesting that these compounds reduced PL enzyme thermostability. In vitro renaturation through urea solution indicated that interactions between PL and EGCG analogs were weak and non-covalent. PMID:25365042

  18. Pancreatitis with normal lipase and amylase in setting of end-stage renal disease.

    PubMed

    Sharma, Anuj; Masood, Umair; Khan, Babar; Chawla, Kunal; Manocha, Divey

    2017-09-01

    Pancreatitis with normal lipase and amylase level is a rare phenomenon. This is especially true in patient with end-stage renal disease as lipase and amylase are renally excreted. Literature review reveals previous case report of pancreatitis with normal lipase and amylase level, however, none of them occurred in the setting of end-stage renal disease. Our case is the first such reported case of pancreatitis in such setting. Here we report a 30year old male with past medical history of end-stage renal disease who presented in emergency department with acute abdominal pain. Laboratory work up revealed normal lipase and amylase level. However, radiological work up was consistent with pancreatitis. This case report highlight the importance of taking the overall clinical picture rather than laboratory work up to rule in or rule out the diagnosis of pancreatitis. Furthermore, this should also serve an important reminder for clinicians to further investigate where clinical suspicion for pancreatitis is high. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Cholecystokinin-stimulated peak lipase concentration in duodenal drainage fluid: a new pancreatic function test.

    PubMed

    Conwell, Darwin L; Zuccaro, Gregory; Morrow, J Brad; Van Lente, Frederick; Obuchowski, Nancy; Vargo, John J; Dumot, John A; Trolli, Patricia; Shay, Steven S

    2002-06-01

    Hormonal stimulation with secretin or cholecystokinin (CCK) is the most sensitive means of assessing pancreatic function. Secretin is not available, and current CCK tests are cumbersome, requiring dual tube intubation and marker perfusion techniques. The aim of this study was to test the efficacy of a new CCK-stimulated pancreatic function test measuring peak lipase concentration. A Dreiling gastroduodenal tube was inserted to the ligament of Treitz, and fluid was collected on ice for 80 min in four 20-min aliquots. CCK was infused i.v. at a constant rate of 40 ng/kg/h. Gastric aspirations were discarded. Duodenal aspirates were analyzed for volume and enzyme concentration with a clinical laboratory autoanalyzer. Nineteen healthy volunteers and 18 chronic pancreatitis patients were studied. Lipase concentration and secretory volume showed a peak response by 40 min of stimulation, whereas amylase response was variable. The mean peak lipase concentrations (+/-SEM) for normal volunteers and mild, moderate, and advanced chronic pancreatitis patients were 16.9+/-1.9, 7.9+/-1.7, 3.7+/-1.2, and 2.1+/-0.6 x 10 5 IU/L, respectively. Lower peak lipase concentrations were significantly associated with more advanced chronic pancreatitis (p < 0.001). The receiver operating characteristic curve area for all chronic pancreatitis patients was 0.944 (95% CI = 0.825-0.985). A peak lipase concentration of 780,000 IU/L provided a sensitivity and specificity of 0.833 and 0.867, respectively. This CCK test was well tolerated and without complications. Lipase concentration in duodenal fluid increases nearly 3-fold from baseline after CCK stimulation in healthy volunteers but is markedly reduced in patients with chronic pancreatic disease. Peak lipase concentration is a significant predictor of chronic pancreatitis and correlates with severity of pancreatic disease. Aspiration of duodenal drainage fluid with a Dreiling tube and analysis with a laboratory autoanalyzer are less cumbersome

  20. Phospholipase A2 as a point of care alternative to serum amylase and pancreatic lipase

    NASA Astrophysics Data System (ADS)

    Liu, Nathan J.; Chapman, Robert; Lin, Yiyang; Bentham, Andrew; Tyreman, Matthew; Philips, Natalie; Khan, Shahid A.; Stevens, Molly M.

    2016-06-01

    Acute pancreatitis is a relatively common and potentially fatal condition, but the presenting symptoms are non-specific and diagnosis relies largely on the measurement of amylase activity by the hospital clinical laboratory. In this work we develop a point of care test for pancreatitis measuring concentration of secretory phospholipase A2 group IB (sPLA2-IB). Novel antibodies for sPLA2-IB were raised and used to design an ELISA and a lateral flow device (LFD) for the point of care measurement of sPLA2-IB concentration, which was compared to pancreatic amylase activity, lipase activity, and sPLA2-IB activity in 153 serum samples. 98 of these samples were obtained from the pathology unit of a major hospital and classified retrospectively according to presence or absence of pancreatitis, and the remaining 55 were obtained from commercial sources to serve as high lipase (n = 20), CA19-9 positive (n = 15), and healthy (n = 20) controls. sPLA2-IB concentration correlated well with the serum activity of both amylase and lipase, and performed at least as well as either markers in the differentiation of pancreatitis from controls.Acute pancreatitis is a relatively common and potentially fatal condition, but the presenting symptoms are non-specific and diagnosis relies largely on the measurement of amylase activity by the hospital clinical laboratory. In this work we develop a point of care test for pancreatitis measuring concentration of secretory phospholipase A2 group IB (sPLA2-IB). Novel antibodies for sPLA2-IB were raised and used to design an ELISA and a lateral flow device (LFD) for the point of care measurement of sPLA2-IB concentration, which was compared to pancreatic amylase activity, lipase activity, and sPLA2-IB activity in 153 serum samples. 98 of these samples were obtained from the pathology unit of a major hospital and classified retrospectively according to presence or absence of pancreatitis, and the remaining 55 were obtained from commercial sources to

  1. Critical evaluation of a specific ELISA and two enzymatic assays of pancreatic lipases in human sera.

    PubMed

    Grandval, Philippe; De Caro, Alain; De Caro, Josiane; Sias, Barbara; Carrière, Frédéric; Verger, Robert; Laugier, René

    2004-01-01

    Human pancreatic lipases (HPL) include the classical HPL, and two related proteins known as pancreatic lipase-related proteins 1 and 2 (HPLRP1 and 2). The aim of this study was to develop an ELISA for specifically quantifying the classical-HPL level in sera of patients with and without pancreatic disorders. The specific activity of various human (including classical-HPL) and microbial lipases was measured using Lipa Vitros and potentiometric (pH-stat) assays. A double sandwich ELISA was also set up, using an anti-classical-HPL polyclonal antibody and a biotinylated monoclonal antibody (mAb 146-40) specific to the classical-HPL. Sera (n = 53) were collected from patients with and without pancreatic disorders. The lipase concentration was deduced from the measured lipolytic activity and compared with the corresponding classical-HPL concentration, measured with the ELISA. Both the purified HPLRP2 and 3 lipases of microbial origin were found to have a significant and unexpected lipolytic activity under the standard Lipa Vitros assay, whereas the ELISA test developed in the present study was found to be specific for the classical-HPL, due to the absence of cross-reactivity between mAb 146-40, HPLRP1 and HPLRP2. The efficiency of the ELISA was assessed in terms of its reproducibility and accuracy. The lower detection limit of classical-HPL was found to be 0.03 microg/l. A good correlation was found to exist between the lipase concentrations obtained in the ELISA, pH-stat and Lipa Vitros tests, in both the control and pathological groups. This is the first time a specific method of measuring classical-HPL in human serum has been proposed. Using this ELISA, we established with the 53 sera selected in the present study, that the Lipa Vitros assay as well as the pH-stat assay were mostly detecting classical pancreatic lipase. However, it is possible that other lipases such as HPLRP2 or lipases of microbial origin, present in some pathological sera, may well interfere with

  2. Inhibitors of pancreatic lipase: state of the art and clinical perspectives

    PubMed Central

    Lunagariya, Nitin A.; Patel, Neeraj K.; Jagtap, Sneha C.; Bhutani, Kamlesh K.

    2014-01-01

    Obesity is a disorder of lipid metabolism and continues to be a global problem, ranking fifth for deaths worldwide. It also leads to diabetes, cardiovascular disorders, musculoskeletal disorders and some types of cancer. Obesity is regarded as the output of a long-term imbalance between energy intake and energy expenditure. Digestion and absorption of dietary lipids by pancreatic lipase, a major source of excess calorie intake, can be targeted for development of anti-obesity agents. Being the major factor of concern, food materials and edible plants are most widely studied for the anti-obesity activity, so that they can be incorporated in the routine diet. In this review, an attempt was made to present a current scenario of the bioactive compounds from plant and microbial origin that have been investigated for their pancreatic lipase inhibition. Compounds belonging to various classes of natural products such as alkaloids, carotenoids, glycosides, polyphenols, polysaccharides, saponins and terpenoids are well studied while lipophilic compounds from microbial sources are the most active against the pancreatic lipase. Few studies on the synthetic analogues, structurally similar to the triglycerides have been described in the review. Despite of tremendous research on the finding of potential pancreatic lipase inhibitor, very few compounds have entered the clinical studies and no new molecule after orlistat has been marketed. Along with HTS based screening, detailed structure-activity relationship studies on semi-synthetic and synthetic derivatives might also provide a direction for the development of potential lead(s) or pharmacophore for pancreatic lipase inhibition in order to treat and/or prevent obesity and related disorders. PMID:26417311

  3. Lipoprotein lipase gene-deficient mice with hypertriglyceridaemia associated with acute pancreatitis.

    PubMed

    Tang, Maochun; Zong, Pengfei; Zhang, Ting; Wang, Dongyan; Wang, Yuhui; Zhao, Yan

    2016-10-01

    To investigate the severity of pancreatitis in lipoprotein lipase (LPL)-deficient hypertriglyceridaemic (HTG) heterozygous mice and to establish an experimental animal model for HTG pancreatitis study. LPL-deficient HTG heterozygous mice were rescued by somatic gene transfer and mated with wild-type mice. The plasma amylase, triglyceride, and pathologic changes in the pancreas of the LPL-deficient HTG heterozygous mice were compared with those of wild-type mice to assess the severity of pancreatitis. In addition, acute pancreatitis (AP) was induced by caerulein (50 µg/kg) for further assessment. The levels of plasma amylase and triglyceride were significantly higher in the LPL-deficient HTG heterozygous mice. According to the pancreatic histopathologic scores, the LPL-deficient HTG heterozygous mice showed more severe pathologic damage than the wild-type mice. Lipoprotein lipase deficient heterozygous mice developed severe caerulein-induced pancreatitis. In addition, their high triglyceride levels were stable. Therefore, LPL-deficient HTG heterozygous mice are a useful experimental model for studying HTG pancreatitis.

  4. Cellulosic fraction of rice bran fibre alters the conformation and inhibits the activity of porcine pancreatic lipase

    USDA-ARS?s Scientific Manuscript database

    The anti-lipase properties of insoluble dietary fiber obtained from rice bran treated with H2SO4 followed by 1.25% KOH were investigated and compared. Porcine pancreatic lipase (PL) adsorbed with higher velocity and saturated at a higher level on the rice bran fibers prepared with higher concentrat...

  5. Hydrolysis of mixed monomolecular films of triglyceride/lecithin by pancreatic lipase.

    PubMed

    Pieroni, G; Verger, R

    1979-10-25

    The main purpose of this study was to describe the influence of lecithin upon lipolysis of mixed monomolecular films of trioctanoylglycerol/didodecanoylphosphatidycholine by pancreatic lipase in order to mimic some physiological situations. The quantity of enzyme adsorbed to the interface was simultaneously determined using 5-thio-2-nitro[14C]benzoyl lipase. Lipolytic activity was enhanced 3- to 4-fold in the presence of colipase, an effect which is attributed to increased enzyme turnover number. When a pure triglyceride film was progressively diluted with lecithin, the minimum specific activity of lipase exhibited a bell-shaped curve: a mixed film containing only 20% trioctanoylglycerol was hydrolyzed at the same rate as a monolayer of pure triglyceride.

  6. Shape based virtual screening and molecular docking towards designing novel pancreatic lipase inhibitors

    PubMed Central

    Veeramachaneni, Ganesh Kumar; Raj, K Kranthi; Chalasani, Leela Madhuri; Annamraju, Sai Krishna; JS, Bondili; Talluri, Venkateswara Rao

    2015-01-01

    Increase in obesity rates and obesity associated health issues became one of the greatest health concerns in the present world population. With alarming increase in obese percentage there is a need to design new drugs related to the obesity targets. Among the various targets linked to obesity, pancreatic lipase was one of the promising targets for obesity treatment. Using the in silico methods like structure based virtual screening, QikProp, docking studies and binding energy calculations three molecules namely zinc85531017, zinc95919096 and zinc33963788 from the natural database were reported as the potential inhibitors for the pancreatic lipase. Among them zinc95919096 presented all the interactions matching to both standard and crystal ligand and hence it can be further proceeded to drug discovery process. PMID:26770027

  7. Medicinal Plants Traditionally Used for Treatment of Obesity and Diabetes Mellitus - Screening for Pancreatic Lipase and α-Amylase Inhibition.

    PubMed

    Buchholz, Tina; Melzig, Matthias F

    2016-02-01

    In order to find new pancreatic lipase (PL) and α-amylase inhibitors from natural sources for the treatment of obesity and related diseases as diabetes mellitus II, 23 medicinal plants with weight-reducing, serum glucose-reducing or related potential were investigated. Methanolic and water extracts of the plants were evaluated by using two in vitro test systems. Our findings have shown that the methanolic extract of Hibiscus sabdariffa L. (Malvaceae) showed high inhibitory activities to PL (IC50 : 35.8 ± 0.8 µg/mL) and α-amylase (IC50 : 29.3 ± 0.5 µg/mL). Furthermore, the methanolic extract of Tamarindus indica L. (Leguminosae) showed a high anti-lipase (IC50 : 152.0 ± 7.0 µg/mL) and the aqueous extract a high anti-amylase (IC50 : 139.4 ± 9.0 µg/mL) activity. This work provides a priority list of interesting plants for further study with respect to the treatment of obesity and associated diseases. Copyright © 2015 John Wiley & Sons, Ltd.

  8. Inhibitory effects of chickpea and Tribulus terrestris on lipase, α-amylase and α-glucosidase.

    PubMed

    Ercan, Pınar; El, Sedef Nehir

    2016-08-15

    The total saponin content and its in vitro bioaccessibilities in Tribulus terrestris and chickpea were determined by a static in vitro digestion method (COST FA1005 Action INFOGEST). Also, in vitro inhibitory effects of the chosen food samples on lipid and starch digestive enzymes were determined by evaluating the lipase, α-amylase and α-glucosidase activities. The tested T. terrestris and chickpea showed inhibitory activity against α-glucosidase (IC50 6967 ± 343 and 2885 ± 85.4 μg/ml, respectively) and α-amylase (IC50 343 ± 26.2 and 167 ± 6.12 μg/ml, respectively). The inhibitory activities of T. terrestris and chickpea against lipase were 15.3 ± 2.03 and 9.74 ± 1.09 μg/ml, respectively. The present study provides the first evidence that these food samples (T. terrestris, chickpea) are potent inhibitors of key enzymes in digestion of carbohydrates and lipids in vitro. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Amylase, Lipase, and Acute Pancreatitis in People With Type 2 Diabetes Treated With Liraglutide: Results From the LEADER Randomized Trial.

    PubMed

    Steinberg, William M; Buse, John B; Ghorbani, Marie Louise Muus; Ørsted, David D; Nauck, Michael A

    2017-07-01

    To evaluate serum amylase and lipase levels and the rate of acute pancreatitis in patients with type 2 diabetes and high cardiovascular risk randomized to liraglutide or placebo and observed for 3.5-5.0 years. A total of 9,340 patients with type 2 diabetes were randomized to either liraglutide or placebo (median observation time 3.84 years). Fasting serum lipase and amylase were monitored. Acute pancreatitis was adjudicated in a blinded manner. Compared with the placebo group, liraglutide-treated patients had increases in serum lipase and amylase of 28.0% and 7.0%, respectively. Levels were increased at 6 months and then remained stable. During the study, 18 (0.4% [1.1 events/1,000 patient-years of observation] [PYO]) liraglutide-treated and 23 (0.5% [1.7 events/1,000 PYO]) placebo patients had acute pancreatitis confirmed by adjudication. Most acute pancreatitis cases occurred ≥12 months after randomization. Liraglutide-treated patients with prior history of pancreatitis ( n = 147) were not more likely to develop acute pancreatitis than similar patients in the placebo group ( n = 120). Elevations of amylase and lipase levels did not predict future risk of acute pancreatitis (positive predictive value <1.0%) in patients treated with liraglutide. In a population with type 2 diabetes at high cardiovascular risk, there were numerically fewer events of acute pancreatitis among liraglutide-treated patients (regardless of previous history of pancreatitis) compared with the placebo group. Liraglutide was associated with increases in serum lipase and amylase, which were not predictive of an event of subsequent acute pancreatitis. © 2017 by the American Diabetes Association.

  10. Prednisone treatment alters the serum amylase and lipase activities in normal dogs without causing pancreatitis.

    PubMed Central

    Fittschen, C; Bellamy, J E

    1984-01-01

    In order to test the hypothesis that treatment with glucocorticoids causes pancreatitis in dogs, 18 mongrel dogs were divided into three groups of six individuals, each group receiving prednisone at different doses orally or intramuscularly for two weeks. Two groups consisting of six dogs each served as controls. Treatment for two weeks with oral prednisone at 1.2 mg/kg body weight or at 4 mg/kg body weight daily decreased the serum amylase activities, but increased the serum lipase activities. Postmortem examinations revealed microscopic evidence of mild pancreatitis in only one dog given prednisone, that clinically appeared normal. It was concluded that daily doses of 4 mg prednisone/kg body weight or less given orally or intramuscularly for two weeks do not cause pancreatitis in dogs. PMID:6202383

  11. [Influence of tobacco smoking on lipase activity in patients with pancreatitis].

    PubMed

    Sliwińska-Mossoń, Mariola; Milnerowicz, Halina

    2005-01-01

    The aim of this study is to prove the influence of tobacco smoking on lipase activity in the blood of smoking and non-smoking health persons and in smoking and non-smoking patients with diagnosed acute (AP), chronic exaggerated (CEP) and chronic pancreatitis (CP). The blood has been collected from 28 healthy persons and 55 patients with AP, CEP and CP. The enzyme activity has been determined using the colorimetric method with substrate 1,2-odilauryl-rac-glycero-3-glutaric acid -(6-methylresorufin) ester. The exposures to tobacco smoke have been examined on the basic of concentration of cotinine in the serum of patients. The highest lipase activity has been found in smoking patients with CEP. It has been noted that the serum lipase activity is significantly higher in smoking and healthy persons (p<0,05) then in non-smoking and healthy patients. However no significant differences have been found between the lipase activity in smoking patients with CP and non-smoking patients with CP. Smoking patients with AP and CEP have been found to have a significantly increased enzyme activity (p>0.01; p>0.05 respectively) when compared to non-smoking patients. Results of examination indicate that tobacco smoking has a significant influence on exocrine function of pancreas.

  12. [Assessment of amylase and lipase levels following puncture biopsy and fine needle aspiration guided by endoscopic ultrasound in pancreatic lesions].

    PubMed

    Membrillo-Romero, Alejandro; Gonzalez-Lanzagorta, Rubén; Rascón-Martínez, Dulce María

    Puncture biopsy and fine needle aspiration guided by endoscopic ultrasound has been used as an effective technique and is quickly becoming the procedure of choice for diagnosis and staging in patients suspected of having pancreatic cancer. This procedure has replaced retrograde cholangiopancreatography and brush cytology due to its higher sensitivity for diagnosis, and lower risk of complications. To assess the levels of pancreatic enzymes amylase and lipase, after the puncture biopsy and fine needle aspiration guided by endoscopic ultrasound in pancreatic lesions and the frequency of post-puncture acute pancreatitis. A longitudinal and descriptive study of consecutive cases was performed on outpatients submitted to puncture biopsy and fine needle aspiration guided by endoscopic ultrasound in pancreatic lesions. Levels of pancreatic enzymes such as amylase and lipase were measured before and after the pancreatic puncture. Finally we documented post-puncture pancreatitis cases. A total of 100 patients who had been diagnosed with solid and cystic lesions were included in the study. Significant elevation was found at twice the reference value for lipase in 5 cases (5%) and for amylase in 2 cases (2%), none had clinical symptoms of acute pancreatitis. Eight (8%) of patients presented with mild nonspecific pain with no enzyme elevation compatible with pancreatitis. Pancreatic biopsy needle aspiration guided by endoscopic ultrasound was associated with a low rate of elevated pancreatic enzymes and there were no cases of post-puncture pancreatitis. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  13. Inhibition of Microbial Lipases by Fatty Acids

    PubMed Central

    Smith, J. L.; Alford, John A.

    1966-01-01

    Addition of lard or sodium oleate to the medium used for lipase production by Pseudomonas fragi resulted in a decreased accumulation of lipase in the culture supernatant fluid without affecting cell growth. The production and activity of lipase was inhibited by lard, sodium oleate, and the salts of other unsaturated fatty acids. Some divalent cations, Tweens, lecithin, and bovine serum prevented oleate inhibition, but did not reverse it. Similar inhibitory actions were observed with Geotrichum candidum lipase, but not with a staphylococcal lipase or pancreatic lipase. A protective effect by protein in crude enzyme preparations is indicated. The ability of oleate to lower surface tension does not appear to be related to its ability to inhibit lipase. PMID:5970458

  14. Lid dynamics of porcine pancreatic lipase in non-aqueous solvents.

    PubMed

    Haque, Neshatul; Prabhu, N Prakash

    2016-10-01

    Understanding the dynamics of enzymes in organic solvents has wider implications on their industrial applications. Pancreatic lipases, which show activity in their lid open-state, demonstrate enhanced activity in organic solvents at higher temperatures. However, the lid dynamics of pancreatic lipases in non-aqueous environment is yet to be clearly understood. Dynamics of porcine pancreatic lipase (PPL) in open and closed conformations was followed in ethanol, toluene, and octanol using molecular simulation methods. In silico double mutant D250V and E254L of PPL (PPLmut-Cl) was created and its lid opening dynamics in water and in octanol was analyzed. PPL showed increase in solvent accessible surface area and decrease in packing density as the polarity of the surrounded solvent decreased. Breaking the interactions between D250-Y115, and D250-E254 in PPLmut-Cl directed the lid to attain open-state conformation. Major energy barriers during the lid movement in water and in octanol were identified. Also, the trajectories of lid movement were found to be different in these solvents. Only the double mutant at higher temperature showed lid opening movement suggesting the essential role of the three residues in holding the lid in closed conformation. The lid opening dynamics was faster in octanol than water suggesting that non-polar solvents favor open conformation of the lid. This study identifies important interactions between the lid and the residues in domain 1 which possibly keeps the lid in closed conformation. Also, it explains the rearrangements of residue-residue interactions during lid opening movement in water and in octanol. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Validation of a commercial 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester lipase assay for diagnosis of canine pancreatitis.

    PubMed

    Goodband, Emily L; Serrano, Gonçalo; Constantino-Casas, Fernando; Archer, Joy; Watson, Penny J; Williams, Tim L

    2018-01-01

    The objectives of this study were fourfold: technical validation of a commercial canine 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester (DGGR) lipase assay, to calculate a reference interval for DGGR lipase by the indirect a posteriori method, to establish biological validity of the assay, and to assess agreement between DGGR lipase and specific canine pancreatic lipase (Spec cPL) assays. Dogs with histologically confirmed acute pancreatitis (n=3), chronic pancreatitis (n=8) and normal pancreatic tissue (n=7) with stored (-80°C) serum samples were identified. Relevant controls were selected. Precision, reproducibility and linearity of DGGR lipase, and the effect of sample haemolysis and freezing, were assessed. Sensitivity and specificity of DGGR lipase and Spec cPL were determined. Agreement between these two parameters was calculated using Cohen's kappa coefficient (κ). The DGGR lipase assay demonstrated excellent precision, reproducibility and linearity. Sample haemolysis and storage at -80°C for 12 months did not influence the assay. DGGR lipase (>245IU/l) and Spec cPL (>400µg/l) both showed poor sensitivity but excellent specificity for acute pancreatitis, and poor to moderate sensitivity but excellent specificity for chronic pancreatitis. Substantial agreement (κ=0.679) was found between DGGR lipase and Spec cPL. The validated DGGR lipase assay had similar sensitivity and specificity for the diagnosis of acute and chronic pancreatitis to Spec cPL. DGGR lipase is a reliable alternative to Spec cPL for the diagnosis of pancreatitis.

  16. Brominated polyunsaturated lipids from the Chinese sponge Xestospongia testudinaria as a new class of pancreatic lipase inhibitors.

    PubMed

    Liang, Lin-Fu; Wang, Ting; Cai, You-Sheng; He, Wen-Fei; Sun, Peng; Li, Yu-Fen; Huang, Qi; Taglialatela-Scafati, Orazio; Wang, He-Yao; Guo, Yue-Wei

    2014-05-22

    Chemical analysis of the Chinese marine sponge Xestospongia testudinaria afforded a library of brominated polyunsaturated lipids including eight new compounds, named xestonarienes A-H (3-10) and thirteen known analogues (11-23). The structures of the new compounds were elucidated by detailed spectroscopic analysis and by comparison with literature data. The isolated lipids were evaluated for their inhibitory activity against pancreatic lipase (PL), an essential enzyme for efficient fat digestion and the major metabolite, 14, exhibited a marked inhibitory activity (IC50 = 3.11 μM), similar to that of the positive control Orlistat (IC50 = 0.78 μM). The preliminary structure-activity relationships on the series of compounds clearly evidenced that a terminal (E)-enyne functionality, a diyne within the chain, and methyl ester group are all key functional groups for the activity of this class of PL inhibitors. Further biological investigation on compound 14 revealed a significant decrease in the plasma triglyceride level following an oral lipid challenge in C57BLKS/J male mice. Acute toxicology study demonstrated that compound 14 was non-toxic up to 1600 mg/kg p.o in mice. This is the first report of the PL inhibitory activity for brominated polyunsaturated lipids and the obtained results qualify compound 14 as a potent and bioavailable drug candidate for a mild and safe treatment to prevent and reduce obesity. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  17. Cloning and seasonal secretion of the pancreatic lipase-related protein 2 present in goat seminal plasma.

    PubMed

    Sias, Barbara; Ferrato, Francine; Pellicer-Rubio, Maria-Teresa; Forgerit, Yvonick; Guillouet, Philippe; Leboeuf, Bernard; Carrière, Frédéric

    2005-01-05

    The storage of frozen semen for artificial insemination is usually performed in the presence of egg yolk or skimmed milk as protective agents. In goats, the use of skimmed milk extenders requires, however, that most of the seminal plasma is removed before dilution of spermatozoa because it is deleterious for their survival. It has been previously demonstrated that a lipase (BUSgp60) secreted by the accessory bulbourethral gland was responsible for the cellular death of goat spermatozoa, through the lipolysis of residual milk lipids and the release of toxic free fatty acids. This lipase was purified from the whole seminal plasma of goat and was found to display both lipase and phospholipase A activities, this latter activity representing the main phospholipase activity detected in goat seminal plasma. Based on its N-terminal amino acid sequence, identical to that of BUSgP60 purified from bulbourethral gland secretion, and the design of degenerated oligonucleotides, the lipase was cloned from total mRNA isolated from bulbourethral gland. DNA sequencing confirmed it was the goat pancreatic-lipase-related protein 2 (GoPLRP2). The physiological role of GoPLRP2 is still unknown but this enzyme might be associated with the reproductive activity of goats. A significant increase in lipase secretion was observed every year in August and the level of lipase activity in the semen remained high till December, i.e., during the breeding season. A parallel increase in the plasmatic levels of testosterone suggested that GoPLRP2 expression might be regulated by sexual hormones. The lipase activity level measured in goat seminal plasma, which could reach 1000 U/ml during the breeding season, was one of the highest lipase activity measured in natural sources, including gastric and pancreatic juices.

  18. Effect of bacterial or porcine lipase with low- or high-fat diets on nutrient absorption in pancreatic-insufficient dogs.

    PubMed

    Suzuki, A; Mizumoto, A; Rerknimitr, R; Sarr, M G; DiMango, E P

    1999-02-01

    Treatment of human exocrine pancreatic insufficiency is suboptimal. This study assessed the effects of bacterial lipase, porcine lipase, and diets on carbohydrate, fat, and protein absorption in pancreatic-insufficient dogs. Dogs were given bacterial or porcine lipase and 3 diets: a 48% carbohydrate, 27% fat, and 25% protein standard diet; a high-carbohydrate, low-fat, and low-protein diet; or a low-carbohydrate, high-fat, and high-protein diet (66%/18%/16% and 21%/43%/36% calories). With the standard diet, coefficient of fat absorption increased dose-dependently with both lipases (P < 0.05), but more fat was absorbed with porcine lipase (P < 0.05); 600, 000 IU of bacterial lipase (240 mg) and 300,000 IU of porcine lipase (18 g) nearly abolished steatorrhea. With 300,000 IU of bacterial lipase or 135,000 IU of porcine lipase, fat absorption was greater with the high-fat and -protein diet (P < 0.05 vs. low-fat and -protein diet). There were no interactions among carbohydrate, fat, and protein absorption. Correcting steatorrhea requires 75 times more porcine than bacterial lipase (18 vs. 240 mg). High-fat and high-protein diets optimize fat absorption with both enzymes. High-fat diets with bacterial or porcine lipase should be evaluated in humans with pancreatic steatorrhea.

  19. A novel lipoprotein lipase gene missense mutation in Chinese patients with severe hypertriglyceridemia and pancreatitis

    PubMed Central

    2014-01-01

    Background Alterations or mutations in the lipoprotein lipase (LPL) gene contribute to severe hypertriglyceridemia (HTG). This study reported on two patients in a Chinese family with LPL gene mutations and severe HTG and acute pancreatitis. Methods Two patients with other five family members were included in this study for DNA-sequences of hyperlipidemia-related genes (such as LPL, APOC2, APOA5, LMF1, and GPIHBP1) and 43 healthy individuals and 70 HTG subjects were included for the screening of LPL gene mutations. Results Both patients were found to have a compound heterozygote for a novel LPL gene mutation (L279V) and a known mutation (A98T). Furthermore, one HTG subject out of 70 was found to carry this novel LPL L279V mutation. Conclusions The data from this study showed that compound heterozygote mutations of A98T and L279V inactivate lipoprotein lipase enzymatic activity and contribute to severe HTG and acute pancreatitis in two Chinese patients. Further study will investigate how these LPL gene mutations genetically inactivate the LPL enzyme. PMID:24646025

  20. Structure of Human Pancreatic Lipase-Related Protein 2 with the Lid in an Open Conformation

    SciTech Connect

    Eydoux, Cecilia; Spinelli, Silvia; Davis, Tara L.

    2008-10-02

    Access to the active site of pancreatic lipase (PL) is controlled by a surface loop, the lid, which normally undergoes conformational changes only upon addition of lipids or amphiphiles. Structures of PL with their lids in the open and functional conformation have required cocrystallization with amphiphiles. Here we report two crystal structures of wild-type and unglycosylated human pancreatic lipase-related protein 2 (HPLRP2) with the lid in an open conformation in the absence of amphiphiles. These structures solved independently are strikingly similar, with some residues of the lid being poorly defined in the electron-density map. The open conformation of the lidmore » is however different from that previously observed in classical liganded PL, suggesting different kinetic properties for HPLRP2. Here we show that the HPLRP2 is directly inhibited by E600, does not present interfacial activation, and acts preferentially on substrates forming monomers or small aggregates (micelles) dispersed in solution like monoglycerides, phospholipids and galactolipids, whereas classical PL displays reverse properties and a high specificity for unsoluble substrates like triglycerides and diglycerides forming oil-in-water interfaces. These biochemical properties imply that the lid of HPLRP2 is likely to spontaneously adopt in solution the open conformation observed in the crystal structure. This open conformation generates a large cavity capable of accommodating the digalactose polar head of galactolipids, similar to that previously observed in the active site of the guinea pig PLRP2, but absent from the classical PL. Most of the structural and kinetic properties of HPLRP2 were found to be different from those of rat PLRP2, the structure of which was previously obtained with the lid in a closed conformation. Our findings illustrate the essential role of the lid in determining the substrate specificity and the mechanism of action of lipases.« less

  1. Structure of human pancreatic lipase-related protein 2 with the lid in an open conformation.

    PubMed

    Eydoux, Cécilia; Spinelli, Silvia; Davis, Tara L; Walker, John R; Seitova, Alma; Dhe-Paganon, Sirano; De Caro, Alain; Cambillau, Christian; Carrière, Frédéric

    2008-09-09

    Access to the active site of pancreatic lipase (PL) is controlled by a surface loop, the lid, which normally undergoes conformational changes only upon addition of lipids or amphiphiles. Structures of PL with their lids in the open and functional conformation have required cocrystallization with amphiphiles. Here we report two crystal structures of wild-type and unglycosylated human pancreatic lipase-related protein 2 (HPLRP2) with the lid in an open conformation in the absence of amphiphiles. These structures solved independently are strikingly similar, with some residues of the lid being poorly defined in the electron-density map. The open conformation of the lid is however different from that previously observed in classical liganded PL, suggesting different kinetic properties for HPLRP2. Here we show that the HPLRP2 is directly inhibited by E600, does not present interfacial activation, and acts preferentially on substrates forming monomers or small aggregates (micelles) dispersed in solution like monoglycerides, phospholipids and galactolipids, whereas classical PL displays reverse properties and a high specificity for unsoluble substrates like triglycerides and diglycerides forming oil-in-water interfaces. These biochemical properties imply that the lid of HPLRP2 is likely to spontaneously adopt in solution the open conformation observed in the crystal structure. This open conformation generates a large cavity capable of accommodating the digalactose polar head of galactolipids, similar to that previously observed in the active site of the guinea pig PLRP2, but absent from the classical PL. Most of the structural and kinetic properties of HPLRP2 were found to be different from those of rat PLRP2, the structure of which was previously obtained with the lid in a closed conformation. Our findings illustrate the essential role of the lid in determining the substrate specificity and the mechanism of action of lipases.

  2. Further biochemical characterization of human pancreatic lipase-related protein 2 expressed in yeast cells.

    PubMed

    Eydoux, Cécilia; De Caro, Josiane; Ferrato, Francine; Boullanger, Paul; Lafont, Dominique; Laugier, René; Carrière, Frédéric; De Caro, Alain

    2007-07-01

    Recombinant human pancreatic lipase-related protein 2 (rHPLRP2) was produced in the protease A-deficient yeast Pichia pastoris. A major protein with a molecular mass of 50 kDa was purified from the culture medium using SP-Sepharose and Mono Q chromatography. The protein was found to be highly sensitive to the proteolytic cleavage of a peptide bond in the lid domain. The proteolytic cleavage process occurring in the lid affected both the lipase and phospholipase activities of rHPLRP2. The substrate specificity of the nonproteolyzed rHPLRP2 was investigated using pH-stat and monomolecular film techniques and various substrates (glycerides, phospholipids, and galactolipids). All of the enzyme activities were maximum at alkaline pH values and decreased in the pH 5-7 range corresponding to the physiological conditions occurring in the duodenum. rHPLRP2 was found to act preferentially on substrates forming small aggregates in solution (monoglycerides, egg phosphatidylcholine, and galactolipids) rather than on emulsified substrates such as triolein and diolein. The activity of rHPLRP2 on monogalactosyldiglyceride and digalactosyldiglyceride monomolecular films was determined and compared with that of guinea pig pancreatic lipase-related protein 2, which shows a large deletion in the lid domain. The presence of a full-length lid domain in rHPLRP2 makes it possible for enzyme activity to occur at higher surface pressures. The finding that the inhibition of nonproteolyzed rHPLRP2 by tetrahydrolipstatin and diethyl-p-nitrophenyl phosphate does not involve any bile salt requirements suggests that the rHPLRP2 lid adopts an open conformation in aqueous media.

  3. Serum trypsin, alpha-amylase and lipase during bombesin stimulation in normal subjects and patients with pancreatic insufficiency.

    PubMed

    Hafkenscheid, J C; Hessels, M; Jansen, J B; Lamers, C B

    1984-01-31

    The effect of infusion of bombesin (60 pmol/kg 20 min) on pancreatic enzymes in serum was studied in 13 normal subjects and 12 patients with pancreatic insufficiency. In normal subjects administration of bombesin induced large increases in serum trypsin (p less than 0.01), while serum total alpha-amylase and pancreatic alpha-amylase did not change and serum lipase showed only a modest rise (0.01 less than p less than 0.05). Patients with pancreatic insufficiency had significantly lower serum concentrations of all enzymes studied (p less than 0.01) and in such patients bombesin did not change the concentrations of pancreatic enzymes in serum. It is concluded that determination of the serum trypsin response to bombesin may be of help in the diagnosis of pancreatic insufficiency.

  4. High-theabrownins instant dark tea product by Aspergillus niger via submerged fermentation: α-glucosidase and pancreatic lipase inhibition and antioxidant activity.

    PubMed

    Wang, Yuwan; Zhang, Mingyue; Zhang, Zhengzhu; Lu, Hengqian; Gao, Xueling; Yue, Pengxiang

    2017-12-01

    Theabrownins (TB) are bioactive components that are usually extracted from Chinese dark tea, in which they are present at low concentrations. The present study aimed to produce an instant dark tea high in theabrownins via submerged fermentation by the fungus Aspergillus niger. Three fermentation parameters that affect theabrownins content (i.e. inoculum size, liquid-solid ratio and rotation speed) were optimized using response surface methodology. Optimum fermentation conditions were modeled to be an inoculum of 5.40% (v/v), a liquid-solid ratio of 27.45 mL g -1 and a rotation speed of 184 rpm and were predicted to yield 292.99 g kg -1 TB. Under these experimentally conditions, the TB content of the instant dark tea was 291.93 g kg -1 . The antioxidant capacity and α-glucosidase and pancreatic lipase inhibitory activities of the high-TB instant black tea were higher than four other typical instant dark tea products. The results of the present study show that careful management of culture conditions can produce a dark tea high in theabrownins. Furthermore, high-theabrownins instant dark tea could serve as a source of bioactive products and be used in functional foods as an ingredient imparting antioxidant properties and the ability to inhibit pancreatic lipase and α-glucosidase. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  5. Amylase, lipase, and volume of drainage fluid in gastrectomy for the early detection of complications caused by pancreatic leakage.

    PubMed

    Seo, Kyung Won; Yoon, Ki Young; Lee, Sang Ho; Shin, Yeon Myung; Choi, Kyung Hyun; Hwang, Hyun Yong

    2011-12-01

    Pancreatic leakage is a serious complication of gastrectomy due to stomach cancer. Therefore, we analyzed amylase and lipase concentrations in blood and drainage fluid, and evaluated the volume of drainage fluid to discern their usefulness as markers for the early detection of serious pancreatic leakage requiring reoperation after gastrectomy. From January 2001 to December 2007, we retrospectively analyzed data from 24,072 patient samples. We divided patients into two groups; 1) complications with pancreatic leakage (CG), and 2) no complications associated with pancreatic leakage (NCG). Values of amylase and lipase in the blood and drainage fluid, volume of the drainage fluid, and relationships among the volumes, amylase values, and lipase values in the drainage fluid were evaluated, respectively in the two groups. The mean amylase values of CG were significantly higher than those of NCG in blood and drainage fluid (P < 0.05). For lipase, statistically significant differences were observed in drainage fluid (P < 0.05). The mean volume (standard deviation) of the drained fluid through the tube between CG (n = 22) and NCG (n = 236) on postoperative day 1 were 368.41 (266.25) and 299.26 (300.28), respectively. There were no statistically significant differences between the groups (P = 0.298). There was a correlation between the amylase and lipase values in the drainage fluid (r = 0.812, P = 0.000). Among postoperative amylase and lipase values in blood and drainage fluid, and the volume of drainage fluid, the amylase in drainage fluid was better differentiated between CG and NCG than other markers. The volume of the drainage fluid did not differ significantly between groups.

  6. Can Serum Pancreatic Amylase and Lipase Levels Be Used as Diagnostic Markers to Distinguish Between Patients With Mucinous Cystic Lesions of the Pancreas, Chronic Pancreatitis, and Pancreatic Ductal Adenocarcinoma?

    PubMed

    Pezzilli, Raffaele; Melzi dʼEril, Gianvico; Barassi, Alessandra

    2016-10-01

    This study aimed to assess the presence of pancreatic hyperenzymemia in patients with pancreatic cystic lesions as compared to other chronic diseases of the pancreas. Ninety-one patients were studied: 32 had mucinous cystic lesions, 35 had chronic pancreatitis (CP), and 24 had pancreatic ductal adenocarcinoma (PDAC). Surgery was carried out in 10 of the 32 patients with mucinous cystic lesion (7 of them had severe dysplasia), in 5 patients with CP, and in 9 patients with PDAC. Abnormally high serum pancreatic isoamylase activity was present in 11 (34.4%) patients with mucinous cystic lesions, in 14 (40.0%) patients with CP, and none in patients with PDAC (P = 0.002); whereas serum lipase activity was abnormally high in 8 (25.0%) patients with mucinous cystic lesion, in 17 (48.6%) patients with CP, and in 3 (12.5%) patients with PDAC (P = 0.009). In 7 patients with mucinous cystic lesions and histologically confirmed severe dysplasia, abnormally high levels of both serum pancreatic amylase and lipase were present in 3 (42.9%) patients. High serum concentrations of pancreatic amylase and lipase were found in no more than half of the patients with mucinous cystic lesions. High levels of pancreatic enzymes were not associated with a greater risk of malignancy.

  7. Human pancreatic lipase-related protein 2: tissular localization along the digestive tract and quantification in pancreatic juice using a specific ELISA.

    PubMed

    Eydoux, Cécilia; Aloulou, Ahmed; De Caro, Josiane; Grandval, Philippe; Laugier, René; Carrière, Frédéric; De Caro, Alain

    2006-10-01

    Human pancreatic lipase-related protein 2 (HPLRP2) was previously found to be secreted by the exocrine pancreas. HPLRP2 shows a high level of activity on galactolipids, and might be involved in the digestion of these common vegetable lipids. Specific antibodies were raised in rabbits using a synthetic HPLRP2 peptide selected for its weak amino acid homology with the corresponding peptides of classical human pancreatic lipase (HPL) and human pancreatic lipase-related protein 1 (HPLRP1). ELISA and Western blotting data showed that these antibodies did not react with HPL or HPLRP1. Various tissues from the digestive tract were subjected to Western blotting analysis with the specific anti-peptide HPLRP2 antibody and the expression of HPLRP2 was detected in the pancreas and colon. An ELISA was developed for specifically measuring the HPLRP2 levels in pure pancreatic juice. This procedure was performed using the anti-peptide HPLRP2 antibody as the captor antibody and a biotinylated anti-HPLRP2 polyclonal antibody as the detector antibody. The lowest HPLRP2 quantification limit was found to be 50 microg/L and the reference range for the present assay was 50 microg-500 microg/L. HPL and HPLRP2 levels were measured using specific ELISAs in pancreatic juice from patients with and without pancreatic disorders. Patients with chronic calcifying pancreatitis (CCP) had significantly lower levels of both HPL and HPLRP2 than the controls subjects. The mean HPLRP2 to HPL ratio was estimated to be 28.30% (w/w) and 23.96% (w/w) in controls subjects and CCP patients, respectively, and the difference was not significant. The levels of HPL and HPLRP2 are therefore similarly reduced in both healthy patients and CCP patients.

  8. Inhibition of phospholipase A1, lipase and galactolipase activities of pancreatic lipase-related protein 2 by methyl arachidonyl fluorophosphonate (MAFP).

    PubMed

    Amara, Sawsan; Delorme, Vincent; Record, Michel; Carrière, Frédéric

    2012-11-01

    Methyl arachidonyl fluorophosphonate (MAFP) is a known inhibitor of cytosolic phospholipase A2 and some other serine enzymes. MAFP was found here to be an irreversible inhibitor of human pancreatic lipase-related protein 2 (HPLRP2), an enzyme displaying lipase, phospholipase A1 and galactolipase activities. In the presence of MAFP, mass spectrometry analysis of HPLRP2 revealed a mass increase of 351Da, suggesting a covalent binding of MAFP to the active site serine residue. When HPLRP2 was pre-incubated with MAFP before measuring residual activity, a direct inhibition of HPLRP2 occurred, confirming that HPLRP2 has an active site freely accessible to solvent and differs from most lipases in solution. HPLRP2 activities on tributyrin (TC4), phosphatidylcholine (PC) and monogalactosyl dioctanoylglycerol (C8-MGDG) were equally inhibited under these conditions. Bile salts were not required to trigger the inhibition, but they significantly increased the rate of HPLRP2 inhibition, probably because of MAFP micellar solubilization. Since HPLRP2 is active on various substrates that self-organize differently in the presence of water, HPLRP2 inhibition by MAFP was tested in the presence of these substrates after adding MAFP in the course of the lipolysis reaction. In this case, the rates of inhibition of lipase, phospholipase A1 and galactolipase activities were not equivalent (triglycerides>PC>MGDG), suggesting different enzyme/inhibitor partitioning between the aqueous phase and lipid aggregates. The inhibition by MAFP of a well identified phospholipase A1 (HPLRP2), present in pancreatic juice and also in human monocytes, indicates that MAFP cannot be used for discriminating phospholipase A2 from A1 activities at the cellular level. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Lipoamidase activity in normal and mutagenized pancreatic cholesterol esterase (bile salt-stimulated lipase).

    PubMed Central

    Hui, D Y; Hayakawa, K; Oizumi, J

    1993-01-01

    Purified human milk lipoamidase was digested with endoproteinase Lys-C and the digested peptides were subjected to gasphase microsequence analysis. The sequencing of three isolated peptides of human milk lipoamidase revealed the identity of this protein with human milk bile salt-stimulated lipase (pancreatic cholesterol esterase). The identity of the cholesterol esterase with lipoamidase was confirmed by expressing a recombinant form of rat pancreatic cholesterol esterase and testing for lipoamidase activity of the recombinant protein. The results showed that the recombinant cholesterol esterase displayed both lipolytic and lipoamidase activities and was capable of hydrolysing triacetin and lipoyl-4-aminobenzoate (LPAB). The mechanisms of the esterase and amidase activities of the enzyme were further tested by determining enzyme activity in a mutagenized cholesterol esterase with a His435-->Gln435 substitution. This mutation has been shown previously to abolish enzyme activity against esterase substrates [DiPersio, Fontaine and Hui (1991) J. Biol. Chem. 266, 4033-4036]. We showed that the mutagenized protein was effective in hydrolysing the amidase substrate LPAB and displayed similar enzyme kinetics to those of the native enzyme. These data indicate that the mechanism for the cholesterol esterase hydrolysis of lipoamides is different from that of the hydrolysis of substrates with an ester linkage. The presence of an enzyme in the gastrointestinal tract capable of both ester and amide hydrolysis suggests an important role for this protein in the digestion and absorption processes. PMID:8471055

  10. Effect of Substrate Concentration and Reaction Time of Aquilaria subintegra Leaves Extract on Inhibition of Pancreatic Lipase

    NASA Astrophysics Data System (ADS)

    Zainal, S.; Musa, M.; Idris, J.; Hamid, K. H. Ku

    2018-05-01

    The purpose of this research are to recovery of pancreatic lipase inhibitor and to study the effect of using different concentration of substrate and reaction time on pancreatic lipase inhibitor. In this research, Aquilaria subintegra mature and fresh leaves was used as a sample. The research was conducted by using hydro-distillation with different concentrations, which are 100 µM, 200 µM and 300 µM and reaction times from 20, 40 and 60 minutes were studied. Based on the results obtained for the samples of phenol, flavonoid, gallic acid and quercetin were 49.30 µg/ml, 314.33 µg/ml, 12.94 µg/ml, and 5.15 µg/ml, respectively.

  11. New Biofuel Integrating Glycerol into Its Composition Through the Use of Covalent Immobilized Pig Pancreatic Lipase

    PubMed Central

    Luna, Diego; Posadillo, Alejandro; Caballero, Verónica; Verdugo, Cristóbal; Bautista, Felipa M.; Romero, Antonio A.; Sancho, Enrique D.; Luna, Carlos; Calero, Juan

    2012-01-01

    By using 1,3-specific Pig Pancreatic lipase (EC 3.1.1.3 or PPL), covalently immobilized on AlPO4/Sepiolite support as biocatalyst, a new second-generation biodiesel was obtained in the transesterification reaction of sunflower oil with ethanol and other alcohols of low molecular weight. The resulting biofuel is composed of fatty acid ethyl esters and monoglycerides (FAEE/MG) blended in a molar relation 2/1. This novel product, which integrates glycerol as monoacylglycerols (MG) into the biofuel composition, has similar physicochemical properties compared to those of conventional biodiesel and also avoids the removal step of this by-product. The biocatalyst was found to be strongly fixed to the inorganic support (75%). Nevertheless, the efficiency of the immobilized enzyme was reduced to half (49.1%) compared to that of the free PPL. The immobilized enzyme showed a remarkable stability as well as a great reusability (more than 40 successive reuses) without a significant loss of its initial catalytic activity. Immobilized and free enzymes exhibited different reaction mechanisms, according to the different results in the Arrhenius parameters (Ln A and Ea). However, the use of supported PPL was found to be very suitable for the repetitive production of biofuel due to its facile recyclability from the reaction mixture. PMID:22949849

  12. A Carboxyl Ester Lipase (CEL) Mutant Causes Chronic Pancreatitis by Forming Intracellular Aggregates That Activate Apoptosis.

    PubMed

    Xiao, Xunjun; Jones, Gabrielle; Sevilla, Wednesday A; Stolz, Donna B; Magee, Kelsey E; Haughney, Margaret; Mukherjee, Amitava; Wang, Yan; Lowe, Mark E

    2016-10-28

    Patients with chronic pancreatitis (CP) frequently have genetic risk factors for disease. Many of the identified genes have been connected to trypsinogen activation or trypsin inactivation. The description of CP in patients with mutations in the variable number of tandem repeat (VNTR) domain of carboxyl ester lipase (CEL) presents an opportunity to study the pathogenesis of CP independently of trypsin pathways. We tested the hypothesis that a deletion and frameshift mutation (C563fsX673) in the CEL VNTR causes CP through proteotoxic gain-of-function activation of maladaptive cell signaling pathways including cell death pathways. HEK293 or AR42J cells were transfected with constructs expressing CEL with 14 repeats in the VNTR (CEL14R) or C563fsX673 CEL (CEL maturity onset diabetes of youth with a deletion mutation in the VNTR (MODY)). In both cell types, CEL MODY formed intracellular aggregates. Secretion of CEL MODY was decreased compared with that of CEL14R. Expression of CEL MODY increased endoplasmic reticulum stress, activated the unfolded protein response, and caused cell death by apoptosis. Our results demonstrate that disorders of protein homeostasis can lead to CP and suggest that novel therapies to decrease the intracellular accumulation of misfolded protein may be successful in some patients with CP. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Constitutive expression of human pancreatic lipase-related protein 1 in Pichia pastoris.

    PubMed

    Aloulou, Ahmed; Grandval, Philippe; De Caro, Josiane; De Caro, Alain; Carrière, Frédéric

    2006-06-01

    High-level constitutive expression of the human pancreatic lipase-related protein 1 (HPLRP1) was achieved using the methylotrophic yeast Pichia pastoris. The HPLRP1 cDNA, including its original leader sequence, was subcloned into the pGAPZB vector and further integrated into the genome of P. pastoris X-33 under the control of the glyceraldehyde 3-phosphate dehydrogenase (GAP) constitutive promoter. A major protein with a molecular mass of 50 kDa was found to be secreted into the culture medium and was identified using anti-HPLRP1 polyclonal antibodies as HPLRP1 recombinant protein. The level of expression reached 100-120 mg of HPLRP1 per liter of culture medium after 40 h, as attested by specific and quantitative enzyme-linked immunosorbent assay. A single cation-exchange chromatography sufficed to obtain a highly purified recombinant HPLRP1 after direct batch adsorption onto S-Sepharose of the HPLRP1 present in the culture medium, at pH 5.5. N-terminal sequencing and mass spectrometry analysis were carried out to monitor the production of the mature protein and to confirm that its signal peptide was properly processed.

  14. Occurrence of pancreatic lipase-related protein-2 in various species and its relationship with herbivore diet.

    PubMed

    De Caro, Josiane; Eydoux, Cécilia; Chérif, Slim; Lebrun, Régine; Gargouri, Youssef; Carrière, Frédéric; De Caro, Alain

    2008-05-01

    The occurrence of classical pancreatic lipase (PL) and pancreatic lipase-related proteins 1 and 2 (PLRP1s and 2) in the pancreas of ten mammalian species (humans, pig, rat, guinea pig, coypu, rabbit, horse, ox, goat and sheep) and two bird species (ostrich and turkey) was investigated. The lipases were purified from delipidated pancreas and identified based on the results of Western blotting analysis with anti-human PLRP2 serum, the catalytic properties and N-terminal microsequencing data. PLRP2s were detected in the pancreas of monogastric herbivorous animals (guinea pig, coypu, rabbit and horse) but not in that of ruminant herbivorous animals (ox, goat and sheep). The pancreas of carnivorous animals (dogs and cats) does not have any detectable PLRP2, but contains high levels of PL and PLRP1. By contrast, the pancreas of omnivorous animals (humans and rats) contains PL, PLRP1 and PLRP2, with the exception of porcine pancreas, where no PLRP2 was detected. In the case of bird (ostrich and turkey) pancreases, only classical PL was detected. The substrate specificity of PLRP2s was investigated using phospholipid micelles and synthetic monomolecular galactolipid films. Like human PLRP2, rabbit and horse PLRP2s are galactolipases. In polygastric herbivorous animals (ruminants), however, galactolipids are hydrolyzed via microbial enzymatic processes (involving galactolipases). The absence of galactolipids in carnivorous animals' diet may explain why no PLRP2s were detected here in the pancreas of these species.

  15. Development and analytical validation of a radioimmunoassay for the measurement of feline pancreatic lipase immunoreactivity in serum

    PubMed Central

    2004-01-01

    Abstract Pancreatitis is recognized as an important cause for morbidity and mortality in cats, but diagnosis remains difficult in many cases. As a first step in trying to identify a better diagnostic tool for feline pancreatitis the objective of this project was to develop and analytically validate a radioimmunoassay for the measurement of feline pancreatic lipase immunoreactivity (fPLI). Feline pancreatic lipase (fPL) was purified from pancreatic tissue and antiserum against fPL was raised in rabbits. Tracer was produced by iodination of fPL using the chloramine T method. A radioimmunoassay was established and analytically validated by determination of sensitivity, dilutional parallelism, spiking recovery, intra-assay variability, and interassay variability. A control range for fPLI in cat serum was established from 30 healthy cats using the central 95th percentile. The sensitivity of the assay was 1.2 μg/L. Observed to expected ratios for serial dilutions ranged from 98.8% to 164.3% for 3 different serum samples. Observed to expected ratios for spiking recovery ranged from 76.9% to 147.6% for 3 different serum samples. Coefficients of variation for intra- and interassay variability for 4 different serum samples were 10.1%, 4.5%, 2.2%, and 3.9% and 24.4%, 15.8%, 16.6%, and 21.3%, respectively. A reference range for fPLI was established as 1.2 to 3.8 μg/L. We conclude that the assay described is sensitive, accurate, and precise with limited linearity in the lower and limited reproducibility in the lower and higher end of the working range. Further studies to evaluate the clinical usefulness of this assay are needed and in progress. PMID:15581227

  16. Molecular identification of a pancreatic lipase-like gene involved in sex pheromone biosynthesis of Bombyx mori.

    PubMed

    Zhang, Song-Dou; Li, Xun; Bin, Zhu; Du, Meng-Fang; Yin, Xin-Ming; An, Shi-Heng

    2014-08-01

    Cytoplasmic lipid droplet (LD) lipolysis is regulated by pheromone biosynthesis activating neuropeptide (PBAN) in Bombyx mori. To elucidate the molecular mechanism of cytoplasm LD lipolysis, the pancreatic lipase-like gene in B. mori pheromone glands (PGs), designated as B. mori pancreatic lipase-like gene (BmPLLG), was identified in this study. Spatial expression analysis revealed that BmPLLG is a ubiquitous gene present in all studied tissues, such as PGs, brain, epidermis, egg, midgut, flight muscle and fat body. Temporal expression analysis showed that the BmPLLG transcript begins to express 96 h before eclosion (-96 h), continues to increase, peaks in newly emerged females and steadily decreases after eclosion. Translational expression analysis of BmPLLG using a prepared antiserum demonstrated that BmPLLG was expressed in an age-dependent pattern at different development stages in B. mori. This finding was similar to the transcript expression pattern. Further RNA interference-mediated knockdown of BmPLLG significantly inhibited bombykol production. Overall, these results demonstrated that BmPLLG is involved in PBAN-induced sex pheromone biosynthesis and release. © 2013 Institute of Zoology, Chinese Academy of Sciences.

  17. Association of postprandial serum triglyceride concentration and serum canine pancreatic lipase immunoreactivity in overweight and obese dogs.

    PubMed

    Verkest, K R; Fleeman, L M; Morton, J M; Groen, S J; Suchodolski, J S; Steiner, J M; Rand, J S

    2012-01-01

    Hypertriglyceridemia has been proposed to contribute to the risk of developing pancreatitis in dogs. To determine associations between postprandial serum triglyceride concentrations and canine pancreatic lipase immunoreactivity (cPLI) concentrations or pancreatic disease. Thirty-five client-owned overweight (n = 25) or obese (n = 10) dogs weighing >10 kg. Healthy dogs were prospectively recruited for a cross-sectional study. Serum triglyceride concentrations were measured before and hourly for 12 hours after a meal. Fasting cPLI and canine trypsin-like immunoreactivity (cTLI) concentrations were assayed. Cut-off values for hypertriglyceridemia were set a priori for fasting (≥ 88, ≥ 177, ≥ 354, ≥ 885 mg/dL) and peak postprandial (≥ 133, ≥ 442, ≥ 885 mg/dL) triglyceride concentrations. The association between hypertriglyceridemia and high cPLI concentrations was assessed by exact logistic regression. Follow-up was performed 4 years later to determine the incidence of pancreatic disease. Eight dogs had peak postprandial triglycerides >442 mg/dL and 3 dogs had fasting serum cPLI concentrations ≥ 400 μg/L. Odds of high cPLI concentrations were 16.7 times higher in dogs with peak postprandial triglyceride concentrations ≥ 442 mg/dL relative to other dogs (P < .001). Fasting triglyceride concentration was not significantly associated with cPLI concentrations. None of the dogs with high triglyceride concentrations and one of the dogs with low fasting and peak postprandial triglyceride concentrations developed clinically important pancreatic disease. Overweight and obese dogs with peak serum postprandial triglyceride concentrations ≥ 442 mg/dL after a standard meal are more likely to have serum cPLI concentrations ≥ 400 μg/L, but did not develop clinically important pancreatic disease. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  18. A pilot study evaluating changes in pancreatic lipase immunoreactivity concentrations in canines treated with L-asparaginase (ASNase), vincristine, or both for lymphoma.

    PubMed

    Wright, Zachary; Steiner, Joerg; Suchodolski, Jan; Rogers, Kenita; Barton, Claudia; Brown, Marjorie

    2009-04-01

    L-asparaginase (ASNase) is a common chemotherapy agent for the treatment of lymphoid malignancies. L-asparaginase has been reported to cause clinical pancreatitis in both humans and canines. Canine pancreatic lipase immunoreactivity (cPLI) is now a common diagnostic tool for evaluating pancreatitis in dogs. A total of 52 dogs were enrolled into this study. Canine pancreatic lipase immunoreactivity (cPLI) concentrations were evaluated before and after administration of ASNase, vincristine, or both. All dogs enrolled in the study were evaluated for signs compatible with clinical pancreatitis. No dogs receiving ASNase alone showed evidence of clinical pancreatitis after administration. Also, there was no statistically significant change in cPLI concentrations before or after treatment. Fourteen percent of dogs that received both vincristine and ASNase concurrently had elevated concentrations of cPLI after treatment. Of the 11 dogs with clinical signs compatible with pancreatitis after any chemotherapy treatment, no dog had a cPLI concentration > 400 microg/dL. In conclusion, ASNase did not cause clinical pancreatitis in this cohort of dogs but larger sample sizes are required to further validate this data.

  19. A pilot study evaluating changes in pancreatic lipase immunoreactivity concentrations in canines treated with L-asparaginase (ASNase), vincristine, or both for lymphoma

    PubMed Central

    Wright, Zachary; Steiner, Joerg; Suchodolski, Jan; Rogers, Kenita; Barton, Claudia; Brown, Marjorie

    2009-01-01

    L-asparaginase (ASNase) is a common chemotherapy agent for the treatment of lymphoid malignancies. L-asparaginase has been reported to cause clinical pancreatitis in both humans and canines. Canine pancreatic lipase immunoreactivity (cPLI) is now a common diagnostic tool for evaluating pancreatitis in dogs. A total of 52 dogs were enrolled into this study. Canine pancreatic lipase immunoreactivity (cPLI) concentrations were evaluated before and after administration of ASNase, vincristine, or both. All dogs enrolled in the study were evaluated for signs compatible with clinical pancreatitis. No dogs receiving ASNase alone showed evidence of clinical pancreatitis after administration. Also, there was no statistically significant change in cPLI concentrations before or after treatment. Fourteen percent of dogs that received both vincristine and ASNase concurrently had elevated concentrations of cPLI after treatment. Of the 11 dogs with clinical signs compatible with pancreatitis after any chemotherapy treatment, no dog had a cPLI concentration > 400 μg/dL. In conclusion, ASNase did not cause clinical pancreatitis in this cohort of dogs but larger sample sizes are required to further validate this data. PMID:19436578

  20. Identification of 1H-indene-(1,3,5,6)-tetrol derivatives as potent pancreatic lipase inhibitors using molecular docking and molecular dynamics approach.

    PubMed

    Kalathiya, Umesh; Padariya, M; Baginski, M

    2016-11-01

    Pancreatic lipase is a potential therapeutic target to treat diet-induced obesity in humans, as obesity-related diseases continue to be a global problem. Despite intensive research on finding potential inhibitors, very few compounds have been introduced to clinical studies. In this work, new chemical scaffold 1H-indene-(1,3,5,6)-tetrol was proposed using knowledge-based approach, and 36 inhibitors were derived by modifying its functional groups at different positions in scaffold. To explore binding affinity and interactions of ligands with protein, CDOCKER and AutoDock programs were used for molecular docking studies. Analyzing results of rigid and flexible docking algorithms, inhibitors C_12, C_24, and C_36 were selected based on different properties and high predicted binding affinities for further analysis. These three inhibitors have different moieties placed at different functional groups in scaffold, and to characterize structural rationales for inhibitory activities of compounds, molecular dynamics simulations were performed (500 nSec). It has been shown through simulations that two structural fragments (indene and indole) in inhibitor can be treated as isosteric structures and their position at binding cleft can be replaced by each other. Taking into account these information, two lines of inhibitors can further be developed, each line based on a different core scaffold, that is, indene/indole. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

  1. Inhibitory Effects of Leptin on Pancreatic α-Cell Function

    PubMed Central

    Tudurí, Eva; Marroquí, Laura; Soriano, Sergi; Ropero, Ana B.; Batista, Thiago M.; Piquer, Sandra; López-Boado, Miguel A.; Carneiro, Everardo M.; Gomis, Ramón; Nadal, Angel; Quesada, Ivan

    2009-01-01

    OBJECTIVE Leptin released from adipocytes plays a key role in the control of food intake, energy balance, and glucose homeostasis. In addition to its central action, leptin directly affects pancreatic β-cells, inhibiting insulin secretion, and, thus, modulating glucose homeostasis. However, despite the importance of glucagon secretion in glucose homeostasis, the role of leptin in α-cell function has not been studied in detail. In the present study, we have investigated this functional interaction. RESEARCH DESIGN AND METHODS The presence of leptin receptors (ObR) was demonstrated by RT-PCR analysis, Western blot, and immunocytochemistry. Electrical activity was analyzed by patch-clamp and Ca2+ signals by confocal microscopy. Exocytosis and glucagon secretion were assessed using fluorescence methods and radioimmunoassay, respectively. RESULTS The expression of several ObR isoforms (a–e) was detected in glucagon-secreting αTC1-9 cells. ObRb, the main isoform involved in leptin signaling, was identified at the protein level in αTC1-9 cells as well as in mouse and human α-cells. The application of leptin (6.25 nmol/l) hyperpolarized the α-cell membrane potential, suppressing the electrical activity induced by 0.5 mmol/l glucose. Additionally, leptin inhibited Ca2+ signaling in αTC1-9 cells and in mouse and human α-cells within intact islets. A similar result occurred with 0.625 nmol/l leptin. These effects were accompanied by a decrease in glucagon secretion from mouse islets and were counteracted by the phosphatidylinositol 3-kinase inhibitor, wortmannin, suggesting the involvement of this pathway in leptin action. CONCLUSIONS These results demonstrate that leptin inhibits α-cell function, and, thus, these cells are involved in the adipoinsular communication. PMID:19401420

  2. Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

    PubMed Central

    2009-01-01

    Background Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. Methods Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases) and 31 patients with severe hypertriglyceridaemia (controls) were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. Results Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS). Conclusion Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during chilhood. PMID:19534808

  3. Closed and open conformations of the lid domain induce different patterns of human pancreatic lipase antigenicity and immunogenicity.

    PubMed

    Halimi, Hubert; De Caro, Josiane; Carrière, Frédéric; De Caro, Alain

    2005-12-01

    Epitope mapping was performed on human pancreatic lipase (HPL) using the SPOTscan method. A set of 146 short (12 amino acid residues) synthetic overlapping peptides covering the entire amino acid sequence of HPL were used to systematically assess the immunoreactivity of antisera raised in rabbits against native HPL, HPL without a lid (HPL(-lid)) and HPL covalently inhibited by diethyl p-nitrophenyl phosphate (DP-HPL). In the latter form of HPL, the lid domain controlling the access to the active site was assumed to exist in the open conformation. All the anti-lipase sera were tested in a direct ELISA, anti-HPL serum showing the greatest antibody titer. Although from the structural point of view, the differences between the various forms of HPL were restricted to the lid domain, differences in the antigenic properties of HPL were observed with the SPOTscan method, and the anti-DP-HPL antibodies showed the strongest reactivity. Most of the peptide stretches recognized included amino acid residues which are accessible at the surface of the lipase, except for those located near the active site. Two small peptides (T173-P180, V199-A207) were identified in the vicinity of the active site, their antipeptide antibodies were produced and their reactivity towards the various forms of HPL was tested in a double sandwich ELISA. No reactivity was observed under these conditions. Two antipeptide antibodies directed against two other selected peptides, P208-V221 (belonging to the beta9 loop) and I245-F258 (belonging to the lid domain) were prepared and found to react much more strongly with DP-HPL than with HPL or HPL(-lid) in a double sandwich ELISA. These antibodies should provide useful tools for monitoring the conformational changes taking place during the opening of the HPL lid domain.

  4. Evaluation of Traditional Indian Antidiabetic Medicinal Plants for Human Pancreatic Amylase Inhibitory Effect In Vitro

    PubMed Central

    Ponnusamy, Sudha; Ravindran, Remya; Zinjarde, Smita; Bhargava, Shobha; Ravi Kumar, Ameeta

    2011-01-01

    Pancreatic α-amylase inhibitors offer an effective strategy to lower the levels of post prandial hyperglycemia via control of starch breakdown. Eleven Ayurvedic Indian medicinal plants with known hypoglycemic properties were subjected to sequential solvent extraction and tested for α-amylase inhibition, in order to assess and evaluate their inhibitory potential on pancreatic α-amylase. Analysis of 91 extracts, showed that 10 exhibited strong Human Pancreatic Amylase (HPA) inhibitory potential. Of these, 6 extracts showed concentration dependent inhibition with IC50 values, namely, cold and hot water extracts from Ficus bengalensis bark (4.4 and 125 μgmL−1), Syzygium cumini seeds (42.1 and 4.1 μgmL−1), isopropanol extracts of Cinnamomum verum leaves (1.0 μgmL−1) and Curcuma longa rhizome (0.16 μgmL−1). The other 4 extracts exhibited concentration independent inhibition, namely, methanol extract of Bixa orellana leaves (49 μgmL−1), isopropanol extract from Murraya koenigii leaves (127 μgmL−1), acetone extracts from C. longa rhizome (7.4 μgmL−1) and Tribulus terrestris seeds (511 μgmL−1). Thus, the probable mechanism of action of the above fractions is due to their inhibitory action on HPA, thereby reducing the rate of starch hydrolysis leading to lowered glucose levels. Phytochemical analysis revealed the presence of alkaloids, proteins, tannins, cardiac glycosides, flavonoids, saponins and steroids as probable inhibitory compounds. PMID:20953430

  5. Intestinal α-glucosidase and some pancreatic enzymes inhibitory effect of hydroalcholic extract of Moringa stenopetala leaves.

    PubMed

    Toma, Alemayehu; Makonnen, Eyasu; Mekonnen, Yelamtsehay; Debella, Asfaw; Addisakwattana, Sirichai

    2014-06-03

    Moringa stenopetala has been used in traditional health systems to treat diabetes mellitus. One of the successful methods to prevent of the onset of diabetes is to control postprandial hyperglycemia by the inhibition of α-glucosidase and pancreatic α-amylase activities, resulting in the aggressive delay of the carbohydrate digestion of absorbable monosaccharides. The aim of the present study is to investigate the effect of the extract of the leaves of Moringa stenopetala on α-glucosidase, pancreatic α-amylase, pancreatic lipase, and pancreatic cholesterol esterase activities, and, therefore find out the relevance of the plant in controlling blood sugar and lipid levels. The dried leaves of Moringa stenopetala were extracted with hydroalcoholic solvent and dried using rotary vapor under reduced pressure. The dried extracts were determined for the total phenolic compounds, flavonoid content and condensed tannins content by using Folin-Ciocateu's reagent, AlCl3 and vanillin assay, respectively. The dried extract of plant-based food was further quantified with respect to intestinal α-glucosidase (maltase and sucrase) inhibition and pancreatic α-amylase inhibition by glucose oxidase method and dinitrosalicylic (DNS) reagent, respectively. The phytochemical analysis indicated that flavonoid, total phenolic, and condensed tannin contents in the extract were 71.73 ± 2.48 mg quercetin equivalent/g of crude extract, 79.81 ± 2.85 mg of gallic acid equivalent/g of crude extract, 8.82 ± 0.77 mg catechin equivalent/g of crude extract, respectively. The extract inhibited intestinal sucrase more than intestinal maltase with IC50 value of 1.47 ± 0.19 mg/ml. It also slightly inhibited pancreatic α-amylase, pancreatic lipase and pancreatic cholesterol esterase. The result demonstrated the beneficial biochemical effects of Moringa stenopetala by inhibiting intestinal α-glucosidase, pancreatic cholesterol esterase and pancreatic lipase activities. A

  6. Intestinal α-glucosidase and some pancreatic enzymes inhibitory effect of hydroalcholic extract of Moringa stenopetala leaves

    PubMed Central

    2014-01-01

    Background Moringa stenopetala has been used in traditional health systems to treat diabetes mellitus. One of the successful methods to prevent of the onset of diabetes is to control postprandial hyperglycemia by the inhibition of α-glucosidase and pancreatic α-amylase activities, resulting in the aggressive delay of the carbohydrate digestion of absorbable monosaccharides. The aim of the present study is to investigate the effect of the extract of the leaves of Moringa stenopetala on α-glucosidase, pancreatic α-amylase, pancreatic lipase, and pancreatic cholesterol esterase activities, and, therefore find out the relevance of the plant in controlling blood sugar and lipid levels. Methods The dried leaves of Moringa stenopetala were extracted with hydroalcoholic solvent and dried using rotary vapor under reduced pressure. The dried extracts were determined for the total phenolic compounds, flavonoid content and condensed tannins content by using Folin-Ciocateu’s reagent, AlCl3 and vanillin assay, respectively. The dried extract of plant-based food was further quantified with respect to intestinal α-glucosidase (maltase and sucrase) inhibition and pancreatic α-amylase inhibition by glucose oxidase method and dinitrosalicylic (DNS) reagent, respectively. Results The phytochemical analysis indicated that flavonoid, total phenolic, and condensed tannin contents in the extract were 71.73 ± 2.48 mg quercetin equivalent/g of crude extract, 79.81 ± 2.85 mg of gallic acid equivalent/g of crude extract, 8.82 ± 0.77 mg catechin equivalent/g of crude extract, respectively. The extract inhibited intestinal sucrase more than intestinal maltase with IC50 value of 1.47 ± 0.19 mg/ml. It also slightly inhibited pancreatic α-amylase, pancreatic lipase and pancreatic cholesterol esterase. Conclusion The result demonstrated the beneficial biochemical effects of Moringa stenopetala by inhibiting intestinal α-glucosidase, pancreatic cholesterol esterase

  7. Coupling of guanine nucleotide inhibitory protein to somatostatin receptors on pancreatic acinar membranes

    SciTech Connect

    Sakamoto, C.; Matozaki, T.; Nagao, M.

    1987-09-01

    Guanine nucleotides and pertussis toxin were used to investigate whether somatostatin receptors interact with the guanine nucleotide inhibitory protein (NI) on pancreatic acinar membranes in the rat. Guanine nucleotides reduced /sup 125/I-(Tyr/sup 1/)somatostatin binding to acinar membranes up to 80%, with rank order of potency being 5'-guanylyl imidodiphosphate (Gpp(NH)p)>GTP>TDP>GMP. Scatchard analysis revealed that the decrease in somatostatin binding caused by Gpp(NH)p was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. The inhibitory effect of Gpp(NH)p was partially abolished in the absence of Mg/sup 2 +/. When pancreatic acini were treated withmore » 1 ..mu..g/ml pertussis toxin for 4 h, subsequent /sup 125/I-(Tyr/sup 1/)somatostatin binding to acinar membranes was reduced. Pertussis toxin treatment also abolished the inhibitory effect of somatostatin on vasoactive intestinal peptide-stimulated increase in cellular content of adenosine 3',5'-cyclic monophosphate (cAMP) in the acini. The present results suggest that 1) somatostatin probably functions in the pancreas to regulate adenylate cyclase enzyme system via Ni, 2) the extent of modification of Ni is correlated with the ability of somatostatin to inhibit cAMP accumulation in acini, and 3) guanine nucleotides also inhibit somatostatin binding to its receptor.« less

  8. Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lep{sup ob/ob} mice

    SciTech Connect

    Sekiya, Motohiro; Yahagi, Naoya, E-mail: nyahagi-tky@umin.ac.jp; Laboratory of Molecular Physiology on Energy Metabolism, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655

    2009-09-25

    It has long been a matter of debate whether the hormone-sensitive lipase (HSL)-mediated lipolysis in pancreatic {beta}-cells can affect insulin secretion through the alteration of lipotoxicity. We generated mice lacking both leptin and HSL (Lep{sup ob/ob}/HSL{sup -/-}) and explored the role of HSL in pancreatic {beta}-cells in the setting of obesity. Lep{sup ob/ob}/HSL{sup -/-} developed elevated blood glucose levels and reduced plasma insulin levels compared with Lep{sup ob/ob}/HSL{sup +/+} in a fed state, while the deficiency of HSL did not affect glucose homeostasis in Lep{sup +/+} background. The deficiency of HSL exacerbated the accumulation of triglycerides in Lep{sup ob/ob} islets,more » leading to reduced glucose-stimulated insulin secretion. The deficiency of HSL also diminished the islet mass in Lep{sup ob/ob} mice due to decreased cell proliferation. In conclusion, HSL affects insulin secretary capacity especially in the setting of obesity.« less

  9. Val-407 and Ile-408 in the β5′-Loop of Pancreatic Lipase Mediate Lipase-Colipase Interactions in the Presence of Bile Salt Micelles*

    PubMed Central

    Freie, Angela Bourbon; Ferrato, Francine; Carrière, Frédéric; Lowe, Mark E.

    2013-01-01

    In a previous study, we demonstrated that the β5′-loop in the C-terminal domain of human pancreatic triglyceride lipase (hPTL) makes a major contribution in the function of hPTL (Chahinian et al. (2002) Biochemistry 41, 13725–13735). In the present study, we characterized the contribution of three residues in the β5′-loop, Val-407, Ile-408, and Leu-412, to the function of hPTL. By substituting charged residues, aspartate or lysine, in these positions, we altered the hydrophilic to lipophilic ratio of the β5′-loop. Each of the mutants was expressed, purified, and characterized for activity and binding with both monolayers and emulsions and for binding to colipase. Experiments with monolayers and with emulsions suggested that the interaction of hPTL with a phospholipid monolayer differs from the interaction of the hPTL-colipase complex with a dicaprin monolayer or a triglyceride emulsion (i.e. neutral lipids). Val-407, Ile-408, and Leu-412 make major contributions to interactions with monolayers, whereas only Val-407 and Ile-408 appear essential for activity on triglyceride emulsions in the presence of bile salt micelles. In solutions of taurodeoxycholate at micellar concentrations, a major effect of the β5′-loop mutations is to change the interaction between hPTL and colipase. These observations support a major contribution of residues in the β5′-loop in the function of hPTL and suggest that a third partner, bile salt micelles or the lipid interface or both, influence the binding of colipase and hPTL through interactions with the β5′-loop. PMID:16431912

  10. Nine Different Chemical Species and Action Mechanisms of Pancreatic Lipase Ligands Screened Out from Forsythia suspensa Leaves All at One Time.

    PubMed

    Chen, Tinggui; Li, Yayun; Zhang, Liwei

    2017-05-12

    It is difficult to screen out as many active components as possible from natural plants all at one time. In this study, subfractions of Forsythia suspensa leaves were firstly prepared; then, their inhibitive abilities on pancreatic lipase were tested; finally, the highest inhibiting subfraction was screened by self-made immobilized pancreatic lipase. Results showed that nine ligands, including eight inhibitors and one promotor, were screened out all at one time. They were three flavonoids (rutin, IC 50 : 149 ± 6.0 μmol/L; hesperidin, 52.4 μmol/L; kaempferol-3- O -rutinoside, isolated from F. suspensa leaves for the first time, IC 50 notably reached 2.9 ± 0.5 μmol/L), two polyphenols (chlorogenic acid, 3150 ± 120 μmol/L; caffeic acid, 1394 ± 52 μmol/L), two lignans (phillyrin, promoter; arctigenin, 2129 ± 10.5 μmol/L), and two phenethyl alcohol (forsythiaside A, 2155 ± 8.5 μmol/L; its isomer). Their action mechanisms included competitive inhibition, competitive promotion, noncompetitive inhibition, and uncompetitive inhibition. In sum, using the appropriate methods, more active ingredients can be simply and quickly screened out all at one time from a complex natural product system. In addition, F. suspensa leaves contain numerous inhibitors of pancreatic lipase.

  11. Serum feline-specific pancreatic lipase immunoreactivity concentrations and abdominal ultrasonographic findings in cats with trauma resulting from high-rise syndrome.

    PubMed

    Zimmermann, Elke; Hittmair, Katharina M; Suchodolski, Jan S; Steiner, Jörg M; Tichy, Alexander; Dupré, Gilles

    2013-05-01

    To evaluate serum feline-specific pancreatic lipase immunoreactivity (fPLI) concentrations and abdominal ultrasonographic findings in cats with trauma resulting from high-rise syndrome. Prospective case series. Animals-34 client-owned cats. From cats evaluated because of high-rise syndrome between March and October 2009, a blood sample was obtained for measurement of serum fPLI concentration within 12 hours after the fall and at 24, 48, and 72 hours after the first blood collection. Pancreatitis was diagnosed in cats with an fPLI concentration > 5.4 μg/L. Each cat had abdominal ultrasonography performed twice 48 hours apart, and pancreatic trauma was assessed via detection of pancreatic enlargement, hypoechoic or heteroechoic pancreatic parenchyma, hyperechoic mesentery, and peritoneal effusion. Cats were assigned 1 point for each abnormality present, and a cumulative score ≥ 3 was considered suggestive of traumatic pancreatitis. Traumatic pancreatitis was diagnosed in 9 and 8 cats on the basis of serum fPLI concentration and ultrasonographic findings, respectively. For cats with pancreatitis, fPLI concentration was significantly higher at 12 and 24 hours after the fall than at 48 and 72 hours after the fall, and serum fPLI concentration decreased as time after the fall increased. Significant agreement existed between the use of serum fPLI concentration and abdominal ultrasonography for the diagnosis of traumatic pancreatitis. Cats with high-rise syndrome often had serum fPLI concentrations > 5.4 μg/L within 12 hours after the fall, and concurrent evaluation of those cats via abdominal ultrasonography twice, 48 hours apart, improved detection of traumatic pancreatitis.

  12. Fucosyltransferase 2 (FUT2) non-secretor status and blood group B are associated with elevated serum lipase activity in asymptomatic subjects, and an increased risk for chronic pancreatitis: a genetic association study.

    PubMed

    Weiss, Frank Ulrich; Schurmann, Claudia; Guenther, Annett; Ernst, Florian; Teumer, Alexander; Mayerle, Julia; Simon, Peter; Völzke, Henry; Radke, Dörte; Greinacher, Andreas; Kuehn, Jens-Peter; Zenker, Martin; Völker, Uwe; Homuth, Georg; Lerch, Markus M

    2015-04-01

    Serum lipase activities above the threefold upper reference limit indicate acute pancreatitis. We investigated whether high lipase activity-within the reference range and in the absence of pancreatitis-are associated with genetic single nucleotide polymorphisms (SNP), and whether these identified SNPs are also associated with clinical pancreatitis. Genome-wide association studies (GWAS) on phenotypes 'serum lipase activity' and 'high serum lipase activity' were conducted including 3966 German volunteers from the population-based Study-of-Health-in-Pomerania (SHIP). Lead SNPs associated on a genome-wide significance level were replicated in two cohorts, 1444 blood donors and 1042 pancreatitis patients. Initial discovery GWAS detected SNPs within or near genes encoding the ABO blood group specifying transferases A/B (ABO), Fucosyltransferase-2 (FUT2), and Chymotrypsinogen-B2 (CTRB2), to be significantly associated with lipase activity levels in asymptomatic subjects. Replication analyses in blood donors confirmed the association of FUT-2 non-secretor status (OR=1.49; p=0.012) and ABO blood-type-B (OR=2.48; p=7.29×10(-8)) with high lipase activity levels. In pancreatitis patients, significant associations were found for FUT-2 non-secretor status (OR=1.53; p=8.56×10(-4)) and ABO-B (OR=1.69, p=1.0×10(-4)) with chronic pancreatitis, but not with acute pancreatitis. Conversely, carriers of blood group O were less frequently affected by chronic pancreatitis (OR=0.62; p=1.22×10(-05)) and less likely to have high lipase activity levels (OR=0.59; p=8.14×10(-05)). These are the first results indicating that ABO blood type-B as well as FUT2 non-secretor status are common population-wide risk factors for developing chronic pancreatitis. They also imply that, even within the reference range, elevated lipase activities may indicate subclinical pancreatic injury in asymptomatic subjects. Published by the BMJ Publishing Group Limited. For permission to use (where not already

  13. Inhibitory effects of rosmarinic acid extracts on porcine pancreatic amylase in vitro.

    PubMed

    McCue, Patrick P; Shetty, Kalidas

    2004-01-01

    Porcine pancreatic alpha-amylase (PPA) was allowed to react with herbal extracts containing rosmarinic acid (RA) and purified RA. The derivatized enzyme-phytochemical mixtures obtained were characterized for residual amylase activity. These in vitro experiments showed that the amylase activity was inhibited in the presence of these phytochemicals. The extent of amylase inhibition correlated with increased concentration of RA. RA-containing oregano extracts yielded higher than expected amylase inhibition than similar amount of purified RA, suggesting that other phenolic compounds or phenolic synergies may contribute to additional amylase inhibitory activity. The significance of food-grade, plant-based amylase inhibitors for modulation of diabetes mellitus and other oxidation-linked diseases is hypothesized and discussed.

  14. Differences in the intramolecular structure of structured oils do not affect pancreatic lipase activity in vitro or the absorption by rats of (n-3) fatty acids.

    PubMed

    Porsgaard, Trine; Xu, Xuebing; Göttsche, Jesper; Mu, Huiling

    2005-07-01

    The fatty acid composition and intramolecular structure of dietary triacylglycerols (TAGs) influence their absorption. We compared the in vitro pancreatic lipase activity and the lymphatic transport in rats of fish oil and 2 enzymatically interesterified oils containing 10:0 and (n-3) PUFAs of marine origin to investigate whether the positional distribution of fatty acids influenced the overall bioavailability of (n-3) PUFAs in the body. The structured oils had the (n-3) PUFA either mainly at the sn-1,3 position (LML, M = medium-chain fatty acid, L = long-chain fatty acid) or mainly at the sn-2 position (MLM). Oils were administered to lymph-cannulated rats and lymph was collected for 24 h. The fatty acid composition as well as the lipid class distribution of lymph samples was determined. In vitro pancreatic lipase activity was greater when fish oil was the substrate than when the structured oils were the substrates (P < 0.001 at 40 min). This was consistent with a greater 8-h recovery of total fatty acids from fish oil compared with the 2 structured oils (P < 0.05). The absorption profiles of MLM and LML in rats and their in vitro rates of lipase activity did not differ. This indicates that the absorption rate is highly influenced by the lipase activity, which in turn is affected by the fatty acid composition and intramolecular structure. The lipid class distribution in lymph collected from the 3 groups of rats did not differ. In conclusion, the intramolecular structure did not affect the overall absorption of (n-3) PUFAs.

  15. Lipolysis of natural long chain and synthetic medium chain galactolipids by pancreatic lipase-related protein 2.

    PubMed

    Amara, Sawsan; Barouh, Nathalie; Lecomte, Jérôme; Lafont, Dominique; Robert, Sylvie; Villeneuve, Pierre; De Caro, Alain; Carrière, Frédéric

    2010-04-01

    Monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) are the most abundant lipids in nature, mainly as important components of plant leaves and chloroplast membranes. Pancreatic lipase-related protein 2 (PLRP2) was previously found to express galactolipase activity, and it is assumed to be the main enzyme involved in the digestion of these common vegetable lipids in the gastrointestinal tract. Most of the previous in vitro studies were however performed with medium chain synthetic galactolipids as substrates. It was shown here that recombinant guinea pig (Cavia porcellus) as well as human PLRP2 hydrolyzed at high rates natural DGDG and MGDG extracted from spinach leaves. Their specific activities were estimated by combining the pH-stat technique, thin layer chromatography coupled to scanning densitometry and gas chromatography. The optimum assay conditions for hydrolysis of these natural long chain galactolipids were investigated and the optimum bile salt to substrate ratio was found to be different from that established with synthetic medium chains MGDG and DGDG. Nevertheless the length of acyl chains and the nature of the galactosyl polar head of the galactolipid did not have major effects on the specific activities of PLRP2, which were found to be very high on both medium chain [1786+/-100 to 5420+/-85U/mg] and long chain [1756+/-208 to 4167+/-167U/mg] galactolipids. Fatty acid composition analysis of natural MGDG, DGDG and their lipolysis products revealed that PLRP2 only hydrolyzed one ester bond at the sn-1 position of galactolipids. PLRP2 might be used to produce lipid and free fatty acid fractions enriched in either 16:3 n-3 or 18:3 n-3 fatty acids, both found at high levels in galactolipids. 2010 Elsevier B.V. All rights reserved.

  16. IR spectroscopy analysis of pancreatic lipase-related protein 2 interaction with phospholipids: 3. Monitoring DPPC lipolysis in mixed micelles.

    PubMed

    Mateos-Diaz, Eduardo; Sutto-Ortiz, Priscila; Sahaka, Moulay; Rodriguez, Jorge A; Carrière, Frédéric

    2018-03-01

    Usual methods for the continuous assay of lipolytic enzyme activities are mainly based on the titration of free fatty acids, surface pressure monitoring or spectrophotometry using substrates labeled with specific probes. These approaches only give a partial information on the chemistry of the lipolysis reaction and additional end-point analyses are often required to quantify both residual substrate and lipolysis products. We used transmission infrared (IR) spectroscopy to monitor simultaneously the hydrolysis of phospholipids by guinea pig pancreatic lipase-related protein 2 (GPLRP2) and the release of lipolysis products. The substrate (DPPC, 1,2-Dipalmitoyl phosphatidylcholine) was mixed with sodium taurodeoxycholate (NaTDC) to form mixed micelles in D 2 O buffer at pD 6 and 8. After hydrogen/deuterium exchange, DPPC hydrolysis by GPLRP2 (100nM) was monitored at 35°C in a liquid cell by recording IR spectra and time-course variations in the CO stretching region. These changes were correlated to variations in the concentrations of DPPC, lysophospholipids (lysoPC) and palmitic acid (Pam) using calibration curves established with these compounds individually mixed with NaTDC. We were thus able to quantify each compound and its time-course variations during the phospholipolysis reaction and to estimate the enzyme activity. To validate the IR analysis, variations in residual DPPC, lysoPC and Pam were also quantified by thin-layer chromatography coupled to densitometry and similar hydrolysis profiles were obtained using both methods. IR spectroscopy can therefore be used to monitor the enzymatic hydrolysis of phospholipids and obtain simultaneously chemical and physicochemical information on substrate and all reaction products (H-bonding, hydration, acyl chain mobility). Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Action of fatty acids on the exocrine pancreatic secretion of the conscious rat: further evidence for a protein pancreatic inhibitory factor.

    PubMed

    Demol, P; Sarles, H

    1978-02-01

    The existence of a delayed inhibition of the secretion of protein by the rat pancreas after intraduodenal injection of oleic acid has been confirmed. 1. This phenomenon is not dependent on the presence or absence of bile or pancreatic juice in the intestine. 2. The action of oleic acid is not a pathological phenomenon due to lesions of the gut mucosa because isotonic solutions of Na oleate dispersed into polysorbate 80 or olive oil (rich in oleic acid) plus pancreatic juice have the same effect. 3. Fatty acids must be free or saponified but not esterified in the form of triglycerides. Triglycerides are only effective if pancreatic juice is simultaneously reintroduced into the duodenum. 4. Oleic acid (C18 monoéne) is more efficient than caprylic acid (C8) and butyric acid (C4) is ineffective. The effect of chain length in releasing the inhibitory factor is therefore approximately the same as in CCK-PZ release. 5. Intraduodenal infusion of hypertonic glucose solution does not inhibit pancreatic protein secretion indicating that release of enteroglucagon is probably not responsible for the inhibition. The inhibitory action of hypertonic NaCl solution is not explained.

  18. Absence of diabetes and pancreatic exocrine dysfunction in a transgenic model of carboxyl-ester lipase-MODY (maturity-onset diabetes of the young).

    PubMed

    Ræder, Helge; Vesterhus, Mette; El Ouaamari, Abdelfattah; Paulo, Joao A; McAllister, Fiona E; Liew, Chong Wee; Hu, Jiang; Kawamori, Dan; Molven, Anders; Gygi, Steven P; Njølstad, Pål R; Kahn, C Ronald; Kulkarni, Rohit N

    2013-01-01

    CEL-MODY is a monogenic form of diabetes with exocrine pancreatic insufficiency caused by mutations in CARBOXYL-ESTER LIPASE (CEL). The pathogenic processes underlying CEL-MODY are poorly understood, and the global knockout mouse model of the CEL gene (CELKO) did not recapitulate the disease. We therefore aimed to create and phenotype a mouse model specifically over-expressing mutated CEL in the pancreas. We established a monotransgenic floxed (flanking LOX sequences) mouse line carrying the human CEL mutation c.1686delT and crossed it with an elastase-Cre mouse to derive a bitransgenic mouse line with pancreas-specific over-expression of CEL carrying this disease-associated mutation (TgCEL). Following confirmation of murine pancreatic expression of the human transgene by real-time quantitative PCR, we phenotyped the mouse model fed a normal chow and compared it with mice fed a 60% high fat diet (HFD) as well as the effects of short-term and long-term cerulein exposure. Pancreatic exocrine function was normal in TgCEL mice on normal chow as assessed by serum lipid and lipid-soluble vitamin levels, fecal elastase and fecal fat absorption, and the normoglycemic mice exhibited normal pancreatic morphology. On 60% HFD, the mice gained weight to the same extent as controls, had normal pancreatic exocrine function and comparable glucose tolerance even after resuming normal diet and follow up up to 22 months of age. The cerulein-exposed TgCEL mice gained weight and remained glucose tolerant, and there were no detectable mutation-specific differences in serum amylase, islet hormones or the extent of pancreatic tissue inflammation. In this murine model of human CEL-MODY diabetes, we did not detect mutation-specific endocrine or exocrine pancreatic phenotypes, in response to altered diets or exposure to cerulein.

  19. Analysis of the discriminative inhibition of mammalian digestive lipases by 3-phenyl substituted 1,3,4-oxadiazol-2(3H)-ones.

    PubMed

    Point, Vanessa; Pavan Kumar, K V P; Marc, Sylvain; Delorme, Vincent; Parsiegla, Goetz; Amara, Sawsan; Carrière, Frédéric; Buono, Gérard; Fotiadu, Frédéric; Canaan, Stéphane; Leclaire, Julien; Cavalier, Jean-François

    2012-12-01

    We report here the reactivity and selectivity of three 5-Methoxy-N-3-Phenyl substituted-1,3,4-Oxadiazol-2(3H)-ones (MPOX, as well as meta and para-PhenoxyPhenyl derivatives, i.e.MmPPOX and MpPPOX) with respect to the inhibition of mammalian digestive lipases: dog gastric lipase (DGL), human (HPL) and porcine (PPL) pancreatic lipases, human (HPLRP2) and guinea pig (GPLRP2) pancreatic lipase-related proteins 2, human pancreatic carboxyl ester hydrolase (hCEH), and porcine pancreatic extracts (PPE). All three oxadiazolones displayed similar inhibitory activities on DGL, PLRP2s and hCEH than the FDA-approved anti-obesity drug Orlistat towards the same enzymes. These compounds appeared however to be discriminative of HPL (poorly inhibited) and PPL (fully inhibited). The inhibitory activities obtained experimentally in vitro were further rationalized using in silico molecular docking. In the case of DGL, we demonstrated that the phenoxy group plays a key role in specific molecular interactions within the lipase's active site. The absence of this group in the case of MPOX, as well as its connectivity to the neighbouring aromatic ring in the case of MmPPOX and MpPPOX, strongly impacts the inhibitory efficiency of these oxadiazolones and leads to a significant gain in selectivity towards the lipases tested. The powerful inhibition of PPL, DGL, PLRP2s, hCEH and to a lesser extend HPL, suggests that oxadiazolone derivatives could also provide useful leads for the development of novel and more discriminative inhibitors of digestive lipases. These inhibitors could be used for a better understanding of individual lipase function as well as for drug development aiming at the regulation of the whole gastrointestinal lipolysis process. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  20. 21 CFR 184.1415 - Animal lipase.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Animal lipase. 184.1415 Section 184.1415 Food and... Substances Affirmed as GRAS § 184.1415 Animal lipase. (a) Animal lipase (CAS Reg. No. 9001-62-1) is an enzyme preparation obtained from edible forestomach tissue of calves, kids, or lambs, or from animal pancreatic...

  1. 21 CFR 184.1415 - Animal lipase.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Animal lipase. 184.1415 Section 184.1415 Food and....1415 Animal lipase. (a) Animal lipase (CAS Reg. No. 9001-62-1) is an enzyme preparation obtained from edible forestomach tissue of calves, kids, or lambs, or from animal pancreatic tissue. The enzyme...

  2. 21 CFR 184.1415 - Animal lipase.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Animal lipase. 184.1415 Section 184.1415 Food and... Substances Affirmed as GRAS § 184.1415 Animal lipase. (a) Animal lipase (CAS Reg. No. 9001-62-1) is an enzyme preparation obtained from edible forestomach tissue of calves, kids, or lambs, or from animal pancreatic...

  3. 21 CFR 184.1415 - Animal lipase.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Animal lipase. 184.1415 Section 184.1415 Food and... Substances Affirmed as GRAS § 184.1415 Animal lipase. (a) Animal lipase (CAS Reg. No. 9001-62-1) is an enzyme preparation obtained from edible forestomach tissue of calves, kids, or lambs, or from animal pancreatic...

  4. 21 CFR 184.1415 - Animal lipase.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Animal lipase. 184.1415 Section 184.1415 Food and... Substances Affirmed as GRAS § 184.1415 Animal lipase. (a) Animal lipase (CAS Reg. No. 9001-62-1) is an enzyme preparation obtained from edible forestomach tissue of calves, kids, or lambs, or from animal pancreatic...

  5. Long-Term Retrospective Analysis of Gene Therapy with Alipogene Tiparvovec and Its Effect on Lipoprotein Lipase Deficiency-Induced Pancreatitis.

    PubMed

    Gaudet, Daniel; Stroes, Erik S; Méthot, Julie; Brisson, Diane; Tremblay, Karine; Bernelot Moens, Sophie J; Iotti, Giorgio; Rastelletti, Irene; Ardigo, Diego; Corzo, Deyanira; Meyer, Christian; Andersen, Marc; Ruszniewski, Philippe; Deakin, Mark; Bruno, Marco J

    2016-11-01

    Alipogene tiparvovec (Glybera) is a gene therapy product approved in Europe under the "exceptional circumstances" pathway as a treatment for lipoprotein lipase deficiency (LPLD), a rare genetic disease resulting in chylomicronemia and a concomitantly increased risk of acute and recurrent pancreatitis, with potentially lethal outcome. This retrospective study analyzed the frequency and severity of pancreatitis in 19 patients with LPLD up to 6 years after a single treatment with alipogene tiparvovec. An independent adjudication board of three pancreas experts, blinded to patient identification and to pre- or post-gene therapy period, performed a retrospective review of data extracted from the patients' medical records and categorized LPLD-related acute abdominal pain events requiring hospital visits and/or hospitalizations based on the adapted 2012 Atlanta diagnostic criteria for pancreatitis. Both entire disease time period data and data from an equal time period before and after gene therapy were analyzed. Events with available medical record information meeting the Atlanta diagnostic criteria were categorized as definite pancreatitis; events treated as pancreatitis but with variable levels of laboratory and imaging data were categorized as probable pancreatitis or acute abdominal pain events. A reduction of approximately 50% was observed in all three categories of the adjudicated post-gene therapy events. Notably, no severe pancreatitis and only one intensive care unit admission was observed in the post-alipogene tiparvovec period. However, important inter- and intraindividual variations in the pre- and post-gene therapy incidence of events were observed. There was no relationship between the posttreatment incidence of events and the number of LPL gene copies injected, the administration of immunosuppressive regimen or the percent triglyceride decrease achieved at 12 weeks (primary end point in the prospective clinical studies). Although a causal relationship

  6. Partial deletion of beta9 loop in pancreatic lipase-related protein 2 reduces enzyme activity with a larger effect on long acyl chain substrates.

    PubMed

    Dridi, Kaouthar; Amara, Sawsan; Bezzine, Sofiane; Rodriguez, Jorge A; Carrière, Frédéric; Gaussier, Hélène

    2013-07-01

    Structural studies on pancreatic lipase have revealed a complex architecture of surface loops surrounding the enzyme active site and potentially involved in interactions with lipids. Two of them, the lid and beta loop, expose a large hydrophobic surface and are considered as acyl chain binding sites based on their interaction with an alkyl phosphonate inhibitor. While the role of the lid in substrate recognition and selectivity has been extensively studied, the implication of beta9 loop in acyl chain stabilization remained hypothetical. The characterization of an enzyme with a natural deletion of the lid, guinea pig pancreatic lipase-related protein 2 (GPLRP2), suggests however an essential contribution of the beta9 loop in the stabilization of the acyl enzyme intermediate formed during the lipolysis reaction. A GPLRP2 mutant with a seven-residue deletion of beta9 loop (GPLRP2-deltabeta9) was produced and its enzyme activity was measured using various substrates (triglycerides, monoglycerides, galactolipids, phospholipids, vinyl esters) with short, medium and long acyl chains. Whatever the substrate tested, GPLRP2-deltabeta9 activity is drastically reduced compared to that of wild-type GPLRP2 and this effect is more pronounced as the length of substrate acyl chain increases. Changes in relative substrate selectivity and stereoselectivity remained however weak. The deletion within beta9 loop has also a negative effect on the rate of enzyme inhibition by alkyl phosphonates. All these findings indicate that the reduced enzyme turnover observed with GPLRP2-deltabeta9 results from a weaker stabilization of the acyl enzyme intermediate due to a loss of hydrophobic interactions.

  7. Chronic pancreatitis.

    PubMed

    DiMagno, Matthew J; DiMagno, Eugene P

    2012-09-01

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

  8. Pancreatitis

    MedlinePlus

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

  9. Synthesis and kinetic evaluation of Cyclophostin and Cyclipostins phosphonate analogs as selective and potent inhibitors of microbial lipases

    PubMed Central

    Point, Vanessa; Malla, Raj K.; Diomande, Sadia; Martin, Benjamin P.; Delorme, Vincent; Carriere, Frederic; Canaan, Stephane; Rath, Nigam P.; Spilling, Christopher D.; Cavalier, Jean-François

    2012-01-01

    New series of customizable diastereomeric cis- and trans-monocyclic enol-phosphonate analogs to Cyclophostin and Cyclipostins were synthesized. Their potencies and mechanisms of inhibition toward six representative lipolytic enzymes belonging to distinct lipase families were examined. With mammalian gastric and pancreatic lipases no inhibition occurred with any of the compounds tested. Conversely, Fusarium solani Cutinase and lipases from Mycobacterium tuberculosis (Rv0183 and LipY) were all fully inactivated. Best inhibitors displayed a cis conformation (H and OMe) and exhibited higher inhibitory activities than the lipase inhibitor Orlistat towards same enzymes. Our results have revealed that chemical group at the γ-carbon of the phosphonate ring strongly impacts the inhibitory efficiency, leading to a significant improvement in selectivity toward a target lipase over another. The powerful and selective inhibition of microbial (fungal and mycobacterial) lipases suggests that these 7-membered monocyclic enol-phosphonates should provide useful leads for the development of novel and highly selective antimicrobial agents. PMID:23095026

  10. Synthesis and kinetic evaluation of cyclophostin and cyclipostins phosphonate analogs as selective and potent inhibitors of microbial lipases.

    PubMed

    Point, Vanessa; Malla, Raj K; Diomande, Sadia; Martin, Benjamin P; Delorme, Vincent; Carriere, Frederic; Canaan, Stephane; Rath, Nigam P; Spilling, Christopher D; Cavalier, Jean-François

    2012-11-26

    A new series of customizable diastereomeric cis- and trans-monocyclic enol-phosphonate analogs to Cyclophostin and Cyclipostins were synthesized. Their potencies and mechanisms of inhibition toward six representative lipolytic enzymes belonging to distinct lipase families were examined. With mammalian gastric and pancreatic lipases no inhibition occurred with any of the compounds tested. Conversely, Fusarium solani Cutinase and lipases from Mycobacterium tuberculosis (Rv0183 and LipY) were all fully inactivated. The best inhibitors displayed a cis conformation (H and OMe) and exhibited higher inhibitory activities than the lipase inhibitor Orlistat toward the same enzymes. Our results have revealed that chemical group at the γ-carbon of the phosphonate ring strongly impacts the inhibitory efficiency, leading to a significant improvement in selectivity toward a target lipase over another. The powerful and selective inhibition of microbial (fungal and mycobacterial) lipases suggests that these seven-membered monocyclic enol-phosphonates should provide useful leads for the development of novel and highly selective antimicrobial agents.

  11. Rapid screening natural-origin lipase inhibitors from hypolipidemic decoctions by ultrafiltration combined with liquid chromatography-mass spectrometry.

    PubMed

    Xiao, Shun; Yu, Runru; Ai, Ni; Fan, Xiaohui

    2015-02-01

    Lipase inhibitors generate hypolipidemic effect that is helpful to control or treat some obesity diseases by inactivating catalytic activity of human pancreatic lipase, a key enzyme involved in triglyceride hydrolysis in vivo. Many traditional Chinese medicine (TCM) formulae have been effectively used to treat obesity and other fat related diseases for centuries and modern biological experiments demonstrate therapeutic effect of these formulae can be linked to their lipid-lowering capability in blood. These observations suggest that these hypolipidemic decoctions (HDs) could be a promising resource of natural-origin lipase inhibitors. This work described a rapid approach for screening lipase inhibitors from four widely used HDs, including Wu-Ling-San (WLS), Ze-Xie decoction (ZX), Xiao-Xian-Xiong decoction (XXX) and Xiao-Chai-Hu decoction (XCH), by ultrafiltration combing with high performance liquid chromatography-mass spectrometry (HPLC-MS). Our results showed sixteen natural-origin lipase inhibitors were discovered and identified by high resolution and multistage mass spectrometry. Inhibitory activities of two compounds were confirmed by a functional assay of lipase, which validated the reliability of our approach. Molecular docking simulation was then performed to investigate potential mechanism of action for these compounds. Together we present an efficient method for rapid screening lipase inhibitors from complex natural products, which can be easily accommodated to other important enzymatic system with therapeutic values. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Lipase inhibition and antiobesity effect of Atractylodes lancea.

    PubMed

    Jiao, Ping; Tseng-Crank, Julie; Corneliusen, Brandon; Yimam, Mesfin; Hodges, Mandee; Hong, Mei; Maurseth, Catherine; Oh, Misun; Kim, Hyunjin; Chu, Min; Jia, Qi

    2014-05-01

    The ethanol extract of Atractylodes lancea rhizome displayed significant lipase inhibition with an IC50 value of 9.06 µg/mL in a human pancreatic lipase assay from high-throughput screening. Bioassay-guided isolation led to the identification of one new polyacetylene, syn-(5E,11E)-3-acetoxy-4-O-(3-methylbutanoyl)-1,5,11-tridecatriene-7,9-diyne-3,4-diol (7), along with six known compounds (1-6). The structure of compound 7 was determined based on the analysis of NMR and MS data. Among these seven lipase inhibitors, the major compound atractylodin (1) showed the highest lipase inhibitory activity (IC50 = 39.12 µM). The antiobesity effect of the ethanol extract of Atractylodes lancea rhizome was evaluated in a high-fat diet-induced obesity mice model at daily dosages of 250 mg/kg and 500 mg/kg body weight for 4 weeks, and treatment with this extract demonstrated a moderate efficacy at the 500 mg/kg dose level. Georg Thieme Verlag KG Stuttgart · New York.

  13. On the role of transforming growth factor-beta in the growth inhibitory effects of retinoic acid in human pancreatic cancer cells.

    PubMed

    Singh, Brahmchetna; Murphy, Richard F; Ding, Xian-Zhong; Roginsky, Alexandra B; Bell, Richard H; Adrian, Thomas E

    2007-12-24

    Retinoids are potent growth inhibitory and differentiating agents in a variety of cancer cell types. We have shown that retinoids induce growth arrest in all pancreatic cancer cell lines studied, regardless of their p53 and differentiation status. However, the mechanism of growth inhibition is not known. Since TGF-beta2 is markedly induced by retinoids in other cancers and mediates MUC4 expression in pancreatic cancer cells, we investigated the role of TGF-beta in retinoic acid-mediated growth inhibition in pancreatic cancer cells. Retinoic acid markedly inhibited proliferation of two cell lines (Capan-2 and Hs766T) in a concentration and time-dependent manner. Retinoic acid increased TGF-beta2 mRNA content and secretion of the active and latent forms of TGF-beta2 (measured by ELISA and bioassay). The concentrations of active and TGF-beta2 secreted in response to 0.1 - 10 muM retinoic acid were between 1-5 pM. TGF-beta2 concentrations within this range also inhibited proliferation. A TGF-beta neutralizing antibody blocked the growth inhibitory effects of retinoic acid in Capan-2 cells and partially inhibitory the effects in Hs766T cells. These findings indicate that TGF-beta can cause growth inhibition of pancreatic cancer cells, in a p53-independent manner. Furthermore, it demonstrates the fundamental role of TGF-beta in growth inhibition in response to retinoic acid treatment is preserved in vitro.

  14. Inhibitory effect of aromatic geranyl derivatives isolated from Heliotropium filifolium on infectious pancreatic necrosis virus replication.

    PubMed

    Modak, Brenda; Sandino, Ana María; Arata, Loredana; Cárdenas-Jirón, Gloria; Torres, René

    2010-02-24

    Infectious pancreatic necrosis is a disease caused by a birnavirus affecting several wild and commercial aquatic organisms. This infectious disease results in significant losses in the farming industry and therefore effective therapeutic agents are needed to control outbreaks caused by this pathogen. Our goal was to evaluate in vitro antiviral effect of a group of natural compounds (geranyl aromatic derivatives) isolated from the resinous exudate of the plant Heliotropium filifolium (Heliotropiaceae), semi-synthetics compounds obtained from them, and the resinous exudate, on CHSE-214 cell line infected with infectious pancreatic necrosis virus (IPNV) using a virus plaque inhibition assay at various concentrations. The compound ester filifolinyl senecionate was the best antiviral with EC(50) 160 microg/mL and a cytotoxic concentration required to reduce cell viability by 50% up to 400 microg/mL. In order to obtain information about the mechanism of the antiviral action, was evaluated the influence of ester filifolinyl senecionate on the viral RNA synthesis. This compound produced inhibition of the synthesis of viral genomic RNA, suggesting that the ester could be interacting with the viral RNA during the viral cycle. Additionally, a preliminary study of the interaction between ester and a sample of single-stranded RNA was studied at the level of theory Restricted Hartree Fock PM3 method. The results showed that the ester formed hydrogen bonds mainly with nitrogenous bases but not with ribose and phosphate. These results allow propose that the ester filifolinyl senecionate is a good candidate for used as antiviral therapy for IPN virus in salmon fry. Copyright 2009 Elsevier B.V. All rights reserved.

  15. Serum pepsinogen-A, canine pancreatic lipase immunoreactivity, and C-reactive protein as prognostic markers in dogs with gastric dilatation-volvulus.

    PubMed

    Israeli, I; Steiner, J; Segev, G; Kass, P H; Suchodolski, J S; Sattasathuchana, P; Bruchim, Y; Yudelevitch, S; Aroch, I

    2012-01-01

    Pepsinogens are proenzymes secreted by gastric chief cells. In humans, their serum concentrations reflect gastric mucosal morphological and functional status. To evaluate serum canine pepsinogen-A (cPG-A), C-reactive protein (CRP), and canine pancreatic lipase immunoreactivity (cPLI) concentrations in dogs with gastric dilatation-volvulus (GDV). Sixty-six dogs presented with GDV and 79 healthy controls. Blood was collected prospectively, and records retrospectively reviewed. Median cPG-A concentration was higher in GDV dogs (median, 397 μg/L; range, 37-5,410) compared to controls (median, cPG-A 304 μg/L; range, 18-848; P = .07). Mortality rate in GDV dogs was 22.7%. In nonsurvivors of GDV, median cPG-A was higher compared to survivors (median, 746 μg/L; range, 128-5,409 versus median, 346; range, 36-1,575, respectively; P = .003). The proportion of dogs with increased cPG-A increased with gastric wall damage score (P = .007). An ROC analysis of cPG-A as a predictor of death showed an area under the curve (AUC) of 0.75, higher than lactate (AUC 0.66), and corresponded to a sensitivity and specificity of 53% and 88%, respectively. CRP was increased in 48 dogs (75%), cPLI was >200 μg/L in 26 dogs (39.4%) and >400 μg/L in 12 dogs (18.2%) but both analytes had no association with outcome. Presurgical cPG-A concentration was positively and significantly associated with gastric wall lesion severity, but, based on ROC analysis, it was only a moderate outcome predictor. CRP and cPLI were commonly increased in dogs with GDV. Copyright © 2012 by the American College of Veterinary Internal Medicine.

  16. IR spectroscopy analysis of pancreatic lipase-related protein 2 interaction with phospholipids: 1. Discriminative recognition of mixed micelles versus liposomes.

    PubMed

    Mateos-Diaz, Eduardo; Bakala N'Goma, Jean-Claude; Byrne, Deborah; Robert, Sylvie; Carrière, Frédéric; Gaussier, Hélène

    2018-03-01

    Guinea pig pancreatic lipase-related protein 2 (GPLRP2) is an interesting model enzyme that can hydrolyze a large set of acylglycerols in vitro but displays however some selectivity depending on the supramolecular structure of substrate and the presence of surfactants like bile salts. We showed that GPLRP2 hydrolyzes 1,2-dipalmitoyl phosphatidylcholine (DPPC) present in mixed micelles with sodium taurodeoxycholate (NaTDC) but not in multilamellar (MLV) and large unilamellar (LUV) vesicles of DPPC. After characterization of these lipid aggregates by dynamic light scattering (DLS), the discriminative recognition of DPPC in DPPC/NaTDC micelles versus MLV and LUV by an inactive variant (S152G) of GPLRP2 to avoid the effect of substrate hydrolysis was investigated using Fourier transform infrared spectroscopy (FTIR). IR spectra were recorded after hydrogen/deuterium exchange, at pD 6 and various temperatures to study phase transitions. We analyzed the methylene asymmetric stretching (ν(CH2) as ), the carbonyl stretching (ν(CO)) and the composite polar head-group vibration bands, first to characterized differences in DPPC micelles and vesicles, and second to estimate the degree of interaction of GPLRP2 S152G with phospholipid. Our results indicate that a significant interaction between GPLRP2 S152G and DPPC is only observed when NaTDC is added to the system to form micelles and this can be explained by the different organization of DPPC in mixed micelles compared to lamellar vesicles (higher hydration of polar head, higher mobility of alkyl chains) that favors GPLRP2 penetration into the phospholipid layer. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Inhibitory activity of cinnamon bark species and their combination effect with acarbose against intestinal α-glucosidase and pancreatic α-amylase.

    PubMed

    Adisakwattana, Sirichai; Lerdsuwankij, Orathai; Poputtachai, Ubonwan; Minipun, Aukkrapon; Suparpprom, Chaturong

    2011-06-01

    Inhibition of α-glucosidase and pancreatic α-amylase is one of the therapeutic approaches for delaying carbohydrate digestion, resulting in reduced postprandial glucose. The aim of this study was to evaluate the phytochemical analysis and the inhibitory effect of various cinnamon bark species against intestinal α-glucosidase and pancreatic α-amylase. The results showed that the content of total phenolic, flavonoid, and condensed tannin ranged from 0.17 to 0.21 g gallic acid equivalent/g extract, from 48.85 to 65.52 mg quercetin equivalent/g extract, and from 0.12 to 0.15 g catechin equivalent/g extract, respectively. The HPLC fingerprints of each cinnamon species were established. Among cinnamon species, Thai cinnamon extract was the most potent inhibitor against the intestinal maltase with the IC(50) values of 0.58 ± 0.01 mg/ml. The findings also showed that Ceylon cinnamon was the most effective intestinal sucrase and pancreatic α-amylase inhibitor with the IC(50) values of 0.42 ± 0.02 and 1.23 ± 0.02 mg/ml, respectively. In addition, cinnamon extracts produced additive inhibition against intestinal α-glucosidase and pancreatic α-amylase when combined with acarbose. These results suggest that cinnamon bark extracts may be potentially useful for the control of postprandial glucose in diabetic patients through inhibition of intestinal α-glucosidase and pancreatic α-amylase.

  18. Inhibition of lipases from Chromobacterium viscosum and Rhizopus oryzae by tetrahydrolipstatin.

    PubMed

    Potthoff, A P; Haalck, L; Spener, F

    1998-01-15

    Tetrahydrolipstatin is known as an inhibitor for pancreatic lipase but not for microbial lipases. In this paper we demonstrate that in the presence of water-insoluble substrates like tributyrin or olive oil, tetrahydrolipstatin inhibits the lipases of Chromobacterium viscosum and Rhizopus oryzae, although with different potency. In contrast to porcine pancreatic lipase, which forms an irreversible and covalent enzyme-inhibitor complex with tetrahydrolipstatin, the inhibition of the microbial lipases is reversible as the inhibitor can be removed from the enzyme-inhibitor complex by solvent extraction. Moreover, after inhibition of Chromobacterium viscosum lipase tetrahydrolipstatin remains chemically unchanged.

  19. Saponin-enriched sea cucumber extracts exhibit an antiobesity effect through inhibition of pancreatic lipase activity and upregulation of LXR-β signaling.

    PubMed

    Guo, Lu; Gao, Ziyang; Zhang, Liuqiang; Guo, Fujiang; Chen, Yan; Li, Yiming; Huang, Cheng

    2016-08-01

    Sea cucumbers have been consumed as tonic, food, and nutrition supplements for many years. The objective of this study is to investigate the antiobesity and lipid-lowering effects of sea cucumber extracts in in vitro and in vivo models and elucidate the mechanism of action of the extracts on obesity and dyslipidemia. The 60% ethanol extracts from the body walls of 10 different sea cucumbers were investigated for the inhibition of pancreatic lipase (PL) activity in vitro. The optimal active extract (SC-3) was further chemically analyzed by LC-MS and UV. And 0.1% and 0.2% of SC-3 was mixed with a high-fat diet to treat C57/BL6 mice for 6 weeks or 2 weeks as preventive and therapeutic study. The body weight, serum, and liver lipid profile in the mice were investigated. The crude extract of Pearsonothuria graeffei Semper (Holothuriidae) inhibited the PL activity by 36.44% of control at 0.5 μg/mL. SC-3 and echinoside A inhibited PL with an IC50 value at 2.86 μg/mL and 0.76 μM. 0.1% of SC-3 reduced the body weight (23.0 ± 0.62 versus 26.3 ± 0.76 g), the serum TC (2.46 ± 0.04 versus 2.83 ± 0.12 mmol/L), TG (0.19 ± 0.08 versus 0.40 ± 0.03 mmo/L), and LDL-c (0.48 ± 0.02 versus 0.51 ± 0.02 mmol/L), and liver TC (1.19 ± 0.17 versus 1.85 ± 0.13 mmol/mg) and TG (6.18 ± 0.92 versus 10.87 ± 0.97 mmol/mg) contents of the obese C57BL/six mice on a high-fat diet. Sea cucumber may be used for developing antiobesity and antihyperlipidemia drugs.

  20. Inhibitory effect of geraniol in combination with gemcitabine on proliferation of BXPC-3 human pancreatic cancer cells.

    PubMed

    Jin, Xiaoxin; Sun, Jichun; Miao, Xiongyong; Liu, Guoli; Zhong, Dewu

    2013-08-01

    To investigate the inhibitory effect of geraniol alone, or in combination with gemcitabine, on the proliferation of BXPC-3 pancreatic cancer cells. BXPC-3 cells were treated under different conditions: with geraniol at 10, 20, 40, 80 and 160 µmol/l each for 24 h, 48 h or 72 h; with 20 µmol/l geraniol for 24 h or 0 h before 20 µmol/l gemcitabine for 24 h; with 20 µmol/l geraniol for 24 h, 48 h and 72 h following 20 µmol/l gemcitabine for 24 h; or with 20 µmol/l gemcitabine alone as a control. Cell proliferation was assessed and changes in cell morphology were assessed by light and fluorescence microscopy. Apoptosis was detected using flow cytometry. Geraniol inhibited BXPC-3 cell proliferation in a time- and dosa-dependent manner. Geraniol alone or combined with gemcitabine induced BXPC-3 cell apoptosis. BXPC-3 inhibition rates with combined treatment were 55.24%, 50.69%, 49.83%, 41.85% and 45.27% following treatment with 20 µmol/l geraniol for 24 h or 0 h before 20 µmol/l gemcitabine for 24 h, or 20 µmol/l geraniol for 24 h, 48 h and 72 h, following 20 µmol/l gemcitabine for 24 h, respectively. Geraniol inhibited the proliferation of BXPC-3 cells. Geraniol significantly increased the antiproliferative and apoptosis-inducing effects of gemcitabine on BXPC-3 cells. Maximum inhibition of BXPC-3 cells was achieved with geraniol treatment for 24 h before gemcitabine treatment.

  1. Role of Lipase from Community-Associated Methicillin-Resistant Staphylococcus aureus Strain USA300 in Hydrolyzing Triglycerides into Growth-Inhibitory Free Fatty Acids

    PubMed Central

    Cadieux, Brigitte; Vijayakumaran, Vithooshan; Bernards, Mark A.; McGavin, Martin J.

    2014-01-01

    Part of the human host innate immune response involves the secretion of bactericidal lipids on the skin and delivery of triglycerides into abscesses to control invading pathogens. Two Staphylococcus aureus lipases, named SAL1 and SAL2, were identified in the community-associated methicillin-resistant S. aureus strain USA300, which, presumably, are produced and function to degrade triglycerides to release free fatty acids. We show that the SAL2 lipase is one of the most abundant proteins secreted by USA300 and is proteolytically processed from the 72-kDa proSAL2 to the 44-kDa mature SAL2 by the metalloprotease aureolysin. We show that spent culture supernatants had lipase activity on both short- and long-chain fatty acid substrates and that deletion of gehB, encoding SAL2, resulted in the complete loss of these activities. With the use of gas chromatography-mass spectrometry, we show that SAL2 hydrolyzed trilinolein to linoleic acid, a fatty acid with known antistaphylococcal properties. When added to cultures of USA300, trilinolein and, to a lesser extent, triolein inhibited growth in a SAL2-dependent manner. This effect was shown to be due to the enzymatic activity of SAL2 on these triglycerides, since the catalytically inactive SAL2 Ser412Ala mutant was incapable of hydrolyzing the triglycerides or yielding delayed growth in their presence. Overall, these results reveal that SAL2 hydrolyzes triglycerides of both short- and long-chain fatty acids and that the released free fatty acids have the potential to cause significant delays in growth, depending on the chemical nature of the free fatty acid. PMID:25225262

  2. Role of lipase from community-associated methicillin-resistant Staphylococcus aureus strain USA300 in hydrolyzing triglycerides into growth-inhibitory free fatty acids.

    PubMed

    Cadieux, Brigitte; Vijayakumaran, Vithooshan; Bernards, Mark A; McGavin, Martin J; Heinrichs, David E

    2014-12-01

    Part of the human host innate immune response involves the secretion of bactericidal lipids on the skin and delivery of triglycerides into abscesses to control invading pathogens. Two Staphylococcus aureus lipases, named SAL1 and SAL2, were identified in the community-associated methicillin-resistant S. aureus strain USA300, which, presumably, are produced and function to degrade triglycerides to release free fatty acids. We show that the SAL2 lipase is one of the most abundant proteins secreted by USA300 and is proteolytically processed from the 72-kDa proSAL2 to the 44-kDa mature SAL2 by the metalloprotease aureolysin. We show that spent culture supernatants had lipase activity on both short- and long-chain fatty acid substrates and that deletion of gehB, encoding SAL2, resulted in the complete loss of these activities. With the use of gas chromatography-mass spectrometry, we show that SAL2 hydrolyzed trilinolein to linoleic acid, a fatty acid with known antistaphylococcal properties. When added to cultures of USA300, trilinolein and, to a lesser extent, triolein inhibited growth in a SAL2-dependent manner. This effect was shown to be due to the enzymatic activity of SAL2 on these triglycerides, since the catalytically inactive SAL2 Ser412Ala mutant was incapable of hydrolyzing the triglycerides or yielding delayed growth in their presence. Overall, these results reveal that SAL2 hydrolyzes triglycerides of both short- and long-chain fatty acids and that the released free fatty acids have the potential to cause significant delays in growth, depending on the chemical nature of the free fatty acid. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  3. Comparison of α-amylase, α-glucosidase and lipase inhibitory activity of the phenolic substances in two black legumes of different genera.

    PubMed

    Tan, Yuqing; Chang, Sam K C; Zhang, Yan

    2017-01-01

    Antioxidant-rich plant foods can inhibit starch and lipid digestions that are relevant to diabetes management. Two high-antioxidant black legumes, black soybean (Glycine max) and black turtle bean (Phaseolus vulgaris), belonging to two different genera were used to investigate their capacity against digestive enzymes. Phenolic substances were compared in crude, semi-purified extracts (semi-purified by XAD-7 column), and fractions (fractionationed by Sephadex LH-20 column) from these two legumes. In addition, their antioxidant capacities and abilities to inhibit digestive enzymes were characterized. Results showed that Fraction V from black soybean was the most effective (IC50: 0.25mg/mL) against α-amylase; Fraction V from black turtle bean was the most potent (IC50: 0.25μg/mL) against α-glucosidase; Fraction IV from black turtle bean was the most powerful (IC50: 76μg/mL) against lipase. Of the pure phenolic compounds tested, myricetin showed the highest inhibition of α-amylase, α-glucosidase and lipase (IC50: 0.38mg/mL, 0.87μg/mL and 15μg/mL, respectively). Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. The effect of diet on the expression of lipase genes in the midgut of the lightbrown apple moth (Epiphyas postvittana Walker; Tortricidae).

    PubMed

    Christeller, J T; Poulton, J; Markwick, N M; Simpson, R M

    2010-02-01

    We have identified lipase-like genes from an Epiphyas postvittana larval midgut EST library. Of the 10 pancreatic lipase family genes, six appear to encode active lipases and four encode inactive lipases, based on the presence/absence of essential catalytic residues. The four gastric lipase family genes appear to encode active proteins. Phylogenetic analysis of 54 lepidopteran pancreatic lipase proteins resolved the clade into five groups of midgut origin and a sixth of non-midgut lipases. The inactive proteins formed two separate groups with highly conserved mutations. The lepidopteran midgut lipases formed a ninth subfamily of pancreatic lipases. Eighteen insect and human gastric lipases were analysed phylogenetically with only very weak support for any groupings. Gene expression was measured in the larval midgut following feeding on five artificial diets and on apple leaves. The artificial diets contained different levels of triacylglycerol, linoleic acid and cholesterol. Significant changes in gene expression (more than 100-fold for active pancreatic lipases) were observed. All the inactive lipases were also highly expressed. The gastric lipase genes were expressed at lower levels and suppressed in larvae feeding on leaves. Together, protein motif analysis and the gene expression data suggest that, in phytophagous lepidopteran larvae, the pancreatic lipases may function in vivo as galactolipases and phospholipases whereas the gastric lipases may function as triacylglycerol hydrolases.

  5. Factors Influencing the Digestibility of Solid Fats: Mammalian and Plant Lipases--Glyceride Structure and Solvent

    DTIC Science & Technology

    1993-05-01

    butter 7 and l-paladtcyl-2-oleoyl-3-stearin 5. Pancreatic lipase digestion of the fats extracted from desert chocolate bars 9 6. Lipase digestion of...of cocoa butter (m.p. 36° C), which consists predominantly (50%) of a TC containing palmitic, stearic, and oleic acids and of 18% of oleoyl distearin...determined. Pancreatic lipase digestion of cocoa butter and palmitoyloleovlstearin Contrary to the results obtained in vivo by Apgar et al.2, only 7% of

  6. Neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1, and carbohydrate antigen 19-9 in pancreatic juice: pathobiologic implications in diagnosing benign and malignant disease of the pancreas.

    PubMed

    Kaur, Sukhwinder; Baine, Michael J; Guha, Sushovan; Ochi, Nobuo; Chakraborty, Subhankar; Mallya, Kavita; Thomas, Colleen; Crook, Julia; Wallace, Michael B; Woodward, Timothy A; Jain, Maneesh; Singh, Shailender; Sasson, Aaron R; Skinner, Verna; Raimondo, Massimo; Batra, Surinder K

    2013-04-01

    Pancreatic diseases pose significant diagnostic challenge as signs and symptoms often overlap. We investigated the potential of pancreatic juice neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1 (MIC-1), and carbohydrate antigen 19-9 (CA19-9) to aid in the diagnosis of patients with symptoms suggestive of pancreatic diseases. A total of 105 chronic pancreatitis (CP), pancreatic cancer (PC), and nonpancreatic nonhealthy (patients with symptoms mimicking pancreatic disease but found to be free of any pancreatic disease) patients underwent endoscopic pancreatic juice collection after secretin stimulation. Neutrophil gelatinase-associated lipocalin and MIC-1 levels were measured by enzyme-linked immunosorbent assay, whereas CA19-9 was measured by radioimmunoassay. Neutrophil gelatinase-associated lipocalin, MIC-1, and CA19-9 were significantly elevated in the pancreatic juice of patients with CP and patients with PC as compared with nonpancreatic nonhealthy controls (P ≤ 0.034). Neutrophil gelatinase-associated lipocalin seemed most promising in differentiating diseased versus nondiseased pancreata (areas under the curve, 0.88-0.91), whereas MIC-1 was found to be higher in patients with PC than in patients with CP (P = 0.043). Interestingly, MIC-1 levels in diabetic patients with PC were higher than in nondiabetic patients with PC (P = 0.030) and diabetic patients with CP (P = 0.087). Carbohydrate antigen 19-9 showed the least ability to distinguish patient groups (areas under the curve, 0.61-0.76). Pancreatic juice neutrophil gelatinase-associated lipocalin shows potential utility in establishing pancreatic etiology in the context of nonspecific symptoms, whereas MIC-1 may aid in differentiating PC from CP.

  7. Comparative study on digestive lipase activities on the self emulsifying excipient Labrasol, medium chain glycerides and PEG esters.

    PubMed

    Fernandez, Sylvie; Jannin, Vincent; Rodier, Jean-David; Ritter, Nicolas; Mahler, Bruno; Carrière, Frédéric

    2007-05-01

    Labrasol is a lipid-based self-emulsifying excipient used in the preparation of lipophilic drugs intended for oral delivery. It is mainly composed of PEG esters and glycerides with medium acyl chains, which are potential substrates for digestive lipases. The hydrolysis of Labrasol by porcine pancreatic extracts, human pancreatic juice and several purified digestive lipases was investigated in the present study. Classical human pancreatic lipase (HPL) and porcine pancreatic lipase, which are the main lipases involved in the digestion of dietary triglycerides, showed very low levels of activity on the entire Labrasol excipient as well as on separated fractions of glycerides and PEG esters. On the other hand, gastric lipase, pancreatic lipase-related protein 2 (PLRP2) and carboxyl ester hydrolase (CEH) showed high specific activities on Labrasol. These lipases were found to hydrolyze the main components of Labrasol (PEG esters and monoglycerides) used as individual substrates, whereas these esters were found to be poor substrates for HPL. The lipolytic activity of pancreatic extracts and human pancreatic juice on Labrasol(R) is therefore mainly due to the combined action of CEH and PLRP2. These two pancreatic enzymes, together with gastric lipase, are probably the main enzymes involved in the in vivo lipolysis of Labrasol taken orally.

  8. In vitro inhibitory effects of plant-based foods and their combinations on intestinal α-glucosidase and pancreatic α-amylase

    PubMed Central

    2012-01-01

    Background Plant-based foods have been used in traditional health systems to treat diabetes mellitus. The successful prevention of the onset of diabetes consists in controlling postprandial hyperglycemia by the inhibition of α-glucosidase and pancreatic α-amylase activities, resulting in aggressive delay of carbohydrate digestion to absorbable monosaccharide. In this study, five plant-based foods were investigated for intestinal α-glucosidase and pancreatic α-amylase. The combined inhibitory effects of plant-based foods were also evaluated. Preliminary phytochemical analysis of plant-based foods was performed in order to determine the total phenolic and flavonoid content. Methods The dried plants of Hibiscus sabdariffa (Roselle), Chrysanthemum indicum (chrysanthemum), Morus alba (mulberry), Aegle marmelos (bael), and Clitoria ternatea (butterfly pea) were extracted with distilled water and dried using spray drying process. The dried extracts were determined for the total phenolic and flavonoid content by using Folin-Ciocateu’s reagent and AlCl3 assay, respectively. The dried extract of plant-based food was further quantified with respect to intestinal α-glucosidase (maltase and sucrase) inhibition and pancreatic α-amylase inhibition by glucose oxidase method and dinitrosalicylic (DNS) reagent, respectively. Results The phytochemical analysis revealed that the total phenolic content of the dried extracts were in the range of 230.3-460.0 mg gallic acid equivalent/g dried extract. The dried extracts contained flavonoid in the range of 50.3-114.8 mg quercetin equivalent/g dried extract. It was noted that the IC50 values of chrysanthemum, mulberry and butterfly pea extracts were 4.24±0.12 mg/ml, 0.59±0.06 mg/ml, and 3.15±0.19 mg/ml, respectively. In addition, the IC50 values of chrysanthemum, mulberry and butterfly pea extracts against intestinal sucrase were 3.85±0.41 mg/ml, 0.94±0.11 mg/ml, and 4.41±0.15 mg/ml, respectively. Furthermore, the IC50 values

  9. In vitro inhibitory effects of plant-based foods and their combinations on intestinal α-glucosidase and pancreatic α-amylase.

    PubMed

    Adisakwattana, Sirichai; Ruengsamran, Thanyachanok; Kampa, Patcharaporn; Sompong, Weerachat

    2012-07-31

    Plant-based foods have been used in traditional health systems to treat diabetes mellitus. The successful prevention of the onset of diabetes consists in controlling postprandial hyperglycemia by the inhibition of α-glucosidase and pancreatic α-amylase activities, resulting in aggressive delay of carbohydrate digestion to absorbable monosaccharide. In this study, five plant-based foods were investigated for intestinal α-glucosidase and pancreatic α-amylase. The combined inhibitory effects of plant-based foods were also evaluated. Preliminary phytochemical analysis of plant-based foods was performed in order to determine the total phenolic and flavonoid content. The dried plants of Hibiscus sabdariffa (Roselle), Chrysanthemum indicum (chrysanthemum), Morus alba (mulberry), Aegle marmelos (bael), and Clitoria ternatea (butterfly pea) were extracted with distilled water and dried using spray drying process. The dried extracts were determined for the total phenolic and flavonoid content by using Folin-Ciocateu's reagent and AlCl3 assay, respectively. The dried extract of plant-based food was further quantified with respect to intestinal α-glucosidase (maltase and sucrase) inhibition and pancreatic α-amylase inhibition by glucose oxidase method and dinitrosalicylic (DNS) reagent, respectively. The phytochemical analysis revealed that the total phenolic content of the dried extracts were in the range of 230.3-460.0 mg gallic acid equivalent/g dried extract. The dried extracts contained flavonoid in the range of 50.3-114.8 mg quercetin equivalent/g dried extract. It was noted that the IC50 values of chrysanthemum, mulberry and butterfly pea extracts were 4.24±0.12 mg/ml, 0.59±0.06 mg/ml, and 3.15±0.19 mg/ml, respectively. In addition, the IC50 values of chrysanthemum, mulberry and butterfly pea extracts against intestinal sucrase were 3.85±0.41 mg/ml, 0.94±0.11 mg/ml, and 4.41±0.15 mg/ml, respectively. Furthermore, the IC50 values of roselle and butterfly pea

  10. Discrimination between closed and open forms of lipases using electrophoretic techniques.

    PubMed

    Miled, N; Riviere, M; Cavalier, J F; Buono, G; Berti, L; Verger, R

    2005-03-15

    The enhanced catalytic activity of lipases is often associated with structural changes. The three-dimensional (3D) structures showed that the covalently inhibited lipases exist under their open conformations, in contrast to their native closed forms. We studied the inhibition of various lipases--human and dog gastric lipases, human pancreatic lipase, and Humicola lanuginosa lipase--by the octyl-undecyl phosphonate inhibitor, and we measured the subsequent modifications of their respective electrophoretic mobility. Furthermore, the experimental values of the isoelectric points found for the native (closed) and inhibited (open) lipases are in agreement with theoretical calculations based on the electrostatic potential. We concluded that there is a significant difference in the isoelectric points between the closed (native) and open (inhibited) conformations of the four lipases investigated. Thus, analysis of the electrophoretic pattern is proposed as an easy experimental tool to differentiate between a closed and an open form of a given lipase.

  11. Inhibition of lipase-catalyzed hydrolysis of emulsified triglyceride oils by low-molecular weight surfactants under simulated gastrointestinal conditions.

    PubMed

    Li, Yan; McClements, David Julian

    2011-10-01

    The effect of low-molecular weight surfactants on the digestibility of lipids in protein-stabilized corn oil-in-water emulsions was studied using an in vitro digestion model. The impact of non-ionic (Tween 20, Tween 80, Brij35), anionic (SDS), and cationic (DTAB) surfactants on the rate and extent of lipid digestion was studied. All surfactants were found to inhibit lipid digestion at sufficiently high concentrations, with half-maximal inhibitory concentrations (IC50) of 1.2% for Tween 20, 0.7% for Tween 80, 2.8% for Brij35, 1.1% for SDS, and 1.4% for DTAB. The effectiveness of the surfactants at inhibiting lipid digestion was therefore not strongly correlated to the electrical characteristics of the surfactant head group, since the IC50 increased in the following order: Tween 80>SDS>Tween 20>DTAB>Brij35. The ability of these low-molecular weight surfactants to inhibit lipid digestion was attributed to a number of potential mechanisms: (i) prevention of lipase/co-lipase adsorption to the oil-water interface; (ii) formation of interfacial complexes; (iii) direct interaction and inactivation of lipase/co-lipase. Interestingly, DTAB increased the rate and extent of lipid digestion when present at relatively low concentrations. This may have been because this cationic surfactant facilitated the adsorption of lipase to the droplet surfaces through electrostatic attraction, or it bound directly to the lipase molecule thereby changing its structure and activity. A number of the surfactants themselves were found to be susceptible to enzyme digestion by pancreatic enzymes in the absence of lipids: Tween 20, Tween 80, Brij35, and DTAB. This work has important implications for the development of emulsion-based delivery systems for food and pharmaceutical applications. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. IR spectroscopy analysis of pancreatic lipase-related protein 2 interaction with phospholipids: 2. Discriminative recognition of various micellar systems and characterization of PLRP2-DPPC-bile salt complexes.

    PubMed

    Mateos-Diaz, Eduardo; Sutto-Ortiz, Priscila; Sahaka, Moulay; Byrne, Deborah; Gaussier, Hélène; Carrière, Frédéric

    2018-03-01

    The interaction of pancreatic lipase-related protein 2 (PLRP2) with various micelles containing phospholipids was investigated using pHstat enzyme activity measurements, differential light scattering, size exclusion chromatography (SEC) and transmission IR spectroscopy. Various micelles of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and lysophosphatidylcholine were prepared with either bile salts (sodium taurodeoxycholate or glycodeoxycholate) or Triton X-100, which are substrate-dispersing agents commonly used for measuring phospholipase activities. PLRP2 displayed a high activity on all phospholipid-bile salt micelles, but was totally inactive on phospholipid-Triton X-100 micelles. These findings clearly differentiate PLRP2 from secreted pancreatic phospholipase A2 which is highly active on both types of micelles. Using an inactive variant of PLRP2, SEC experiments allowed identifying two populations of PLRP2-DPPC-bile salt complexes corresponding to a high molecular weight 1:1 PLRP2-micelle association and to a low molecular weight association of PLRP2 with few monomers of DPPC/bile salts. IR spectroscopy analysis showed how DPPC-bile salt micelles differ from DPPC-Triton X-100 micelles by a higher fluidity of acyl chains and higher hydration/H-bonding of the interfacial carbonyl region. The presence of bile salts allowed observing changes in the IR spectrum of DPPC upon addition of PLRP2 (higher rigidity of acyl chains, dehydration of the interfacial carbonyl region), while no change was observed with Triton X-100. The differences between these surfactants and their impact on substrate recognition by PLRP2 are discussed, as well as the mechanism by which high and low molecular weight PLRP2-DPPC-bile salt complexes may be involved in the overall process of DPPC hydrolysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Mechanisms of lipase maturation

    PubMed Central

    Péterfy, Miklós

    2010-01-01

    Lipases are acyl hydrolases that represent a diverse group of enzymes present in organisms ranging from prokaryotes to humans. This article focuses on an evolutionarily related family of extracellular lipases that include lipoprotein lipase, hepatic lipase and endothelial lipase. As newly synthesized proteins, these lipases undergo a series of co- and post-translational maturation steps occurring in the endoplasmic reticulum, including glycosylation and glycan processing, and protein folding and subunit assembly. This article identifies and discusses mechanisms that direct early and late events in lipase folding and assembly. Lipase maturation employs the two general chaperone systems operating in the endoplasmic reticulum, as well as a recently identified lipase-specific chaperone termed lipase maturation factor 1. We propose that the two general chaperone systems act in a coordinated manner early in lipase maturation in order to help create partially folded monomers; lipase maturation factor 1 then facilitates final monomer folding and subunit assembly into fully functional homodimers. Once maturation is complete, the lipases exit the endoplasmic reticulum and are secreted to extracellular sites, where they carry out a number of functions related to lipoprotein and lipid metabolism. PMID:20543905

  14. Severe hypertriglyceridemia due to two novel loss-of-function lipoprotein lipase gene mutations (C310R/E396V) in a Chinese family associated with recurrent acute pancreatitis.

    PubMed

    Lun, Yu; Sun, Xiaofang; Wang, Ping; Chi, Jingwei; Hou, Xu; Wang, Yangang

    2017-07-18

    Lipoprotein lipase (LPL) is widely expressed in skeletal muscles, cardiac muscles as well as adipose tissue and involved in the catabolism of triglyceride. Herein we have systematically characterized two novel loss-of-function mutations in LPL from a Chinese family in which afflicted members were manifested by severe hypertriglyceridemia and recurrent pancreatitis. DNA sequencing revealed that the proband was a heterozygote carrying a novel c.T928C (p.C310R) mutation in exon 6 of the LPL gene. Another member of the family was detected to be a compound heterozygote who along with the c.T928C mutation also carried a novel missense mutation c.A1187T (p.E396V) in exon 8 of the LPL gene. Furthermore, COS-1 cells were transfected with lentiviruses containing the mutant LPL genes. While C310R markedly reduced the overall LPL protein level, COS-1 cells carrying E396V or double mutations contained similar overall LPL protein levels to the wild-type. The specific activity of the LPL mutants remained at comparable magnitude to the wild-type. However, few LPL were detected in the culture medium for the mutants, suggesting that both mutations caused aberrant triglyceride catabolism. More specifically, E396V and double mutations dampened the transport of LPL to the cell surface, while for the C310R mutation, reducing LPL protein level might be involved. By characterizing these two novel LPL mutations, this study has expanded our understanding on the pathogenesis of familial hypertriglyceridemia (FHTG).

  15. PPARγ regulates exocrine pancreas lipase.

    PubMed

    Danino, Hila; Naor, Ronny Peri-; Fogel, Chen; Ben-Harosh, Yael; Kadir, Rotem; Salem, Hagit; Birk, Ruth

    2016-12-01

    Pancreatic lipase (triacylglycerol lipase EC 3.1.1.3) is an essential enzyme in hydrolysis of dietary fat. Dietary fat, especially polyunsaturated fatty acids (PUFA), regulate pancreatic lipase (PNLIP); however, the molecular mechanism underlying this regulation is mostly unknown. As PUFA are known to regulate expression of proliferator-activated receptor gamma (PPARγ), and as we identified in-silico putative PPARγ binding sites within the putative PNLIP promoter sequence, we hypothesized that PUFA regulation of PNLIP might be mediated by PPARγ. We used in silico bioinformatics tools, reporter luciferase assay, PPARγ agonists and antagonists, PPARγ overexpression in exocrine pancreas AR42J and primary cells to study PPARγ regulation of PNLIP. Using in silico bioinformatics tools we mapped PPARγ binding sites (PPRE) to the putative promoter region of PNLIP. Reporter luciferase assay in AR42J rat exocrine pancreas acinar cells transfected with various constructs of the putative PNLIP promoter showed that PNLIP transcription is significantly enhanced by PPARγ dose-dependently, reaching maximal levels with multi PPRE sites. This effect was significantly augmented in the presence of PPARγ agonists and reduced by PPARγ antagonists or mutagenesis abrogating PPRE sites. Over-expression of PPARγ significantly elevated PNLIP transcript and protein levels in AR42J cells and in primary pancreas cells. Moreover, PNLIP expression was up-regulated by PPARγ agonists (pioglitazone and 15dPGJ2) and significantly down-regulated by PPARγ antagonists in non-transfected rat exocrine pancreas AR42J cell line cells. PPARγ transcriptionally regulates PNLIP gene expression. This transcript regulation resolves part of the missing link between dietary PUFA direct regulation of PNLIP. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Acid Lipase Disease

    MedlinePlus

    ... of Neurological Disorders and Stroke conducts and supports research to understand lipid storage diseases such as acid lipase deficiency and ... of Neurological Disorders and Stroke conducts and supports research to understand lipid storage diseases such as acid lipase deficiency and ...

  17. Scolopendra subspinipes mutilans protected the cerulein-induced acute pancreatitis by inhibiting high-mobility group box protein-1.

    PubMed

    Jo, Il-Joo; Bae, Gi-Sang; Park, Kyoung-Chel; Choi, Sun Bok; Jung, Won-Seok; Jung, Su-Young; Cho, Jung-Hee; Choi, Mee-Ok; Song, Ho-Joon; Park, Sung-Joo

    2013-03-14

    To evaluate the inhibitory effects of Scolopendra subspinipes mutilans (SSM) on cerulein-induced acute pancreatitis (AP) in a mouse model. SSM water extract (0.1, 0.5, or 1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. Once AP developed, the stable cholecystokinin analogue, cerulein was injected hourly, over a 6 h period. Blood samples were taken 6 h later to determine serum amylase, lipase, and cytokine levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. To specify the role of SSM in pancreatitis, the pancreatic acinar cells were isolated using collagenase method. Then the cells were pre-treated with SSM, then stimulated with cerulein. The cell viability, cytokine productions and high-mobility group box protein-1 (HMGB-1) were measured. Furthermore, the regulating mechanisms of SSM action were evaluated. The administration of SSM significantly attenuated the severity of pancreatitis and pancreatitis associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization and necrosis. SSM treatment also reduced pancreatic weight/body weight ratio, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-α and interleukin-1β. In addition, treatment with SSM inhibited HMGB-1 expression in the pancreas during AP. In accordance with in vivo data, SSM inhibited the cerulein-induced acinar cell death, cytokine, and HMGB-1 release. SSM also inhibited the activation of c-Jun NH2-terminal kinase, p38 and nuclear factor (NF)-κB. These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase, p38 and NF-κB.

  18. Scolopendra subspinipes mutilans protected the cerulein-induced acute pancreatitis by inhibiting high-mobility group box protein-1

    PubMed Central

    Jo, Il-Joo; Bae, Gi-Sang; Park, Kyoung-Chel; Choi, Sun Bok; Jung, Won-Seok; Jung, Su-Young; Cho, Jung-Hee; Choi, Mee-Ok; Song, Ho-Joon; Park, Sung-Joo

    2013-01-01

    AIM: To evaluate the inhibitory effects of Scolopendra subspinipes mutilans (SSM) on cerulein-induced acute pancreatitis (AP) in a mouse model. METHODS: SSM water extract (0.1, 0.5, or 1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. Once AP developed, the stable cholecystokinin analogue, cerulein was injected hourly, over a 6 h period. Blood samples were taken 6 h later to determine serum amylase, lipase, and cytokine levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. To specify the role of SSM in pancreatitis, the pancreatic acinar cells were isolated using collagenase method. Then the cells were pre-treated with SSM, then stimulated with cerulein. The cell viability, cytokine productions and high-mobility group box protein-1 (HMGB-1) were measured. Furthermore, the regulating mechanisms of SSM action were evaluated. RESULTS: The administration of SSM significantly attenuated the severity of pancreatitis and pancreatitis associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization and necrosis. SSM treatment also reduced pancreatic weight/body weight ratio, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-α and interleukin-1β. In addition, treatment with SSM inhibited HMGB-1 expression in the pancreas during AP. In accordance with in vivo data, SSM inhibited the cerulein-induced acinar cell death, cytokine, and HMGB-1 release. SSM also inhibited the activation of c-Jun NH2-terminal kinase, p38 and nuclear factor (NF)-κB. CONCLUSION: These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase, p38 and NF-κB. PMID:23539679

  19. [The efficacy of the combined use of 5-fluorouracil electrophoresis and magnetotherapy in experimental pancreatitis].

    PubMed

    Kents, V V; Tsympilova, T A; Mavrodiĭ, V M; Godlevskiĭ, L S

    1994-01-01

    As shown on the experimental model of rat acute pancreatitis, an intensive 5-fluorouracil electrophoresis course in combination with magnetotherapy significantly reduces the activity of blood trypsin, amylase, lipase and corticosterone. The treatment is thought effective in experimental pancreatitis.

  20. Investigation of the Potential Health Benefits as Lipase Inhibitor and Antioxidant of Leopoldia comosa (L.) Parl.: Variability of Chemical Composition of Wild and Cultivated Bulbs.

    PubMed

    Marrelli, Mariangela; La Grotteria, Stefania; Araniti, Fabrizio; Conforti, Filomena

    2017-09-01

    There is a great interest in the nutritional value of vegetables and fruits and how the habitat affects nutritive and biological properties. In vitro studies here reported were performed to evaluate the inhibitory activity of formulations from edible plant on pancreatic lipase. The aim of this study was also to evaluate the biovariability of L. comosa (L.) Parl. bulbs from Italy. The wild bulbs were compared with the same cultivated species that are commonly commercialized to identify samples with the best quality for a potential therapeutic application. Hydroalcoholic extract and polar fraction of wild bulbs showed a very important pancreatic lipase inhibitory activity, with IC 50 values of 0.166 ± 0.005 and 0.153 ± 0.005 mg/mL, respectively. In order to characterize the extracts, gas chromatography associated with mass spectrometry (GC/MS) analysis was performed, revealing the predominance of palmitic acid. Phenolic and flavonoid composition was also evaluated. L. comosa extract obtained from wild bulbs demonstrated both antioxidant and anti-obesity activities that might be attributed to a wide range of present phenolic compounds.

  1. Single agent BMS-911543 Jak2 inhibitor has distinct inhibitory effects on STAT5 signaling in genetically engineered mice with pancreatic cancer

    PubMed Central

    Mace, Thomas A.; Shakya, Reena; Elnaggar, Omar; Wilson, Kristin; Komar, Hannah M.; Yang, Jennifer; Pitarresi, Jason R.; Young, Gregory S.; Ostrowski, Michael C.; Ludwig, Thomas; Bekaii-Saab, Tanios; Bloomston, Mark; Lesinski, Gregory B.

    2015-01-01

    The Jak/STAT pathway is activated in human pancreatic ductal adenocarcinoma (PDAC) and cooperates with mutant Kras to drive initiation and progression of PDAC in murine models. We hypothesized that the small-molecule Jak2 inhibitor (BMS-911543) would elicit anti-tumor activity against PDAC and decrease immune suppressive features of the disease. We used an aggressive genetically engineered PDAC model with mutant KrasG12D, tp53R270H, and Brca1 alleles (KPC-Brca1 mice). Mice with confirmed tumor burden were treated orally with vehicle or 30 mg/kg BMS-911543 daily for 14 days. Histologic analysis of pancreata from treated mice revealed fewer foci of adenocarcinoma and significantly decreased Ki67+ cells versus controls. In vivo administration of BMS-911543 significantly reduced pSTAT5 and FoxP3 positive cells within the pancreas, but did not alter STAT3 phosphorylation. Continuous dosing of KPC-Brca1 mice with BMS-911543 resulted in a median survival of 108 days, as compared to a median survival of 87 days in vehicle treated animals, a 23% increase (p = 0.055). In vitro experiments demonstrated that PDAC cell lines were poorly sensitive to BMS-911543, requiring high micromolar concentrations to achieve targeted inhibition of Jak/STAT signaling. Similarly, BMS-911543 had little in vitro effect on the viability of both murine and human PDAC-derived stellate cell lines. However, BMS-911543 potently inhibited phosphorylation of pSTAT3 and pSTAT5 at low micromolar doses in human PBMC and reduced in vitro differentiation of Foxp3+ T regulatory cells. These results indicate that single agent Jak2i deserves further study in preclinical models of PDAC and has distinct inhibitory effects on STAT5 mediated signaling. PMID:26575024

  2. Inhibitory effects of epigallocatechin-3-gallate on cell proliferation and the expression of HIF-1α and P-gp in the human pancreatic carcinoma cell line PANC-1.

    PubMed

    Zhu, Zhenni; Wang, Yu; Liu, Zhiqing; Wang, Fan; Zhao, Qiu

    2012-05-01

    The aim of this study was to verify the inhibitory effects of epigallocatechin-3-gallate (EGCG) on cell proliferation and the expression of hypoxia-inducible factor 1 (HIF-1α) and multidrug resistance protein 1 (MDR1/P-gp) in the human pancreatic carcinoma cell line PANC-1, thereby, reversing drug resistance of pancreatic carcinoma and improving its sensitivity to cancer chemotherapy. The human pancreatic carcinoma cell line PANC-1 was incubated under hypoxic conditions with different concentrations of epigallocatechin-3-gallate (EGCG) for indicated hours. The effects of EGCG on the mRNA or protein expression of HIF-1α and MDR1 were determined by RT-PCR or western blotting. Cellular proliferation and viability assays were measured using Cell Counting Kit-8. Western blotting revealed that EGCG inhibits the expression of the HIF-1α protein in a dose-dependent manner, while RT-PCR showed that it does not have any effects on HIF-1α mRNA. In addition, EGCG attenuated the mRNA and protein levels of P-gp in a dose-dependent manner, reaching a peak at the highest concentration. Furthermore, EGCG inhibited the proliferation of PANC-1 cells in a concentration- and time-dependent manner. The attenuation of HIF-1α and the consequently reduced P-gp could contribute to the inhibitory effects of EGCG on the proliferation of PANC-1 cells.

  3. Synthesis of Triptorelin Lactate Catalyzed by Lipase in Organic Media

    PubMed Central

    Zhuang, Hong; Wang, Zhi; Wang, Jiaxin; Zhang, Hong; Xun, Erna; Chen, Ge; Yue, Hong; Tang, Ning; Wang, Lei

    2012-01-01

    Triptorelin lactate was successfully synthesized by porcine pancreatic lipase (PPL) in organic solvents. The effects of acyl donor, substrate ratio, organic solvent, temperature, and water activity were investigated. Under the optimum conditions, a yield of 30% for its ester could be achieved in the reaction for about 48 h. PMID:22949842

  4. Synthesis of triptorelin lactate catalyzed by lipase in organic media.

    PubMed

    Zhuang, Hong; Wang, Zhi; Wang, Jiaxin; Zhang, Hong; Xun, Erna; Chen, Ge; Yue, Hong; Tang, Ning; Wang, Lei

    2012-01-01

    Triptorelin lactate was successfully synthesized by porcine pancreatic lipase (PPL) in organic solvents. The effects of acyl donor, substrate ratio, organic solvent, temperature, and water activity were investigated. Under the optimum conditions, a yield of 30% for its ester could be achieved in the reaction for about 48 h.

  5. Dependence of PERT endpoint on endogenous lipase activity.

    PubMed

    Gao, Wen-Yi; Mulberg, Andrew E

    2014-11-01

    To clarify and to understand the potential for misinterpretation of change in fecal fat quantitation during pancreatic enzyme replacement therapy (PERT) trials for treatment of exocrine pancreatic insufficiency. Analysis of clinical trials submitted to the U.S. Food and Drug Administration (FDA) for approval of PERT that enrolled 123 cystic fibrosis adult and pediatric patients treated with Creon, Pertzye, Ultresa, and Zenpep. The CFA% defines lipase activity as a percentage of converting substrate of "Total Daily Dietary Fat Intake." PERT trials performed to date have modified the definition to converting the "Shared Daily Fat Intake," generating "Partial CFA" for the exogenous lipase: the higher the activity of coexisting endogenous lipase, the lower the "Partial CFA" of exogenous measured. This review shows that "Partial CFA" is not CFA. Enrollment of patients with low HPLA during treatment may improve the interpretability of "Partial CFA" measured by PERT trials.

  6. Lipase-specific foldases.

    PubMed

    Rosenau, Frank; Tommassen, Jan; Jaeger, Karl-Erich

    2004-02-06

    Lipases represent the most important class of enzymes used in biotechnology. Many bacteria produce and secrete lipases but the enzymes originating from Pseudomonas and Burkholderia species seem to be particularly useful for a wide variety of different biocatalytic applications. These enzymes are usually encoded in an operon together with a second gene which codes for a lipase-specific foldase, Lif, which is necessary to obtain enzymatically active lipase. A detailed analysis based on amino acid homology has suggested the classification of Lif proteins into four different families and also revealed the presence of a conserved motif, Rx1x2FDY(F/C)L(S/T)A. Recent experimental evidence suggests that Lifs are so-called steric chaperones, which exert their physiological function by lowering energetic barriers during the folding of their cognate lipases, thereby providing essential steric information needed to fold lipases into their enzymatically active conformation.

  7. Comparison of immunoreactive serum trypsinogen and lipase in Cystic Fibrosis

    SciTech Connect

    Lloyd-Still, J.D.; Weiss, S.; Wessel, H.

    1984-01-01

    The incidence of Cystic Fibrosis (CF) is 1 in 2,000. Early detection and treatment of CF may necessitate newborn screening with a reliable and cost-effective test. Serum immunoreactive trypsinogen (IRT) an enzyme produced by the pancreas, is detectable by radioimmunoassay (RIA) techniques. Recently, it has been shown that IRT is elevated in CF infants for the first few months of life and levels become subnormal as pancreatic insufficiency progresses. Other enzymes produced by the pancreas, such as lipase, are also elevated during this time. The author's earlier work confirmed previous reports of elevated IRT levels in CF infants. The developmentmore » of a new RIA for lipase (nuclipase) has enabled comparison of these 2 pancreatic enzymes in C.F. Serum IRT and lipase determinations were performed on 2 groups of CF patients; infants under 1 year of age, and children between 1 and 18 years of age. Control populations of the same age groups were included. The results showed that both trypsin (161 +- 92 ng/ml, range 20 to 400) and lipase (167 +- 151 ng/ml, range 29 to 500) are elevated in CF in the majority of infants. Control infants had values of IRT ranging from 20 to 29.5 ng/ml and lipase values ranging from 23 to 34 ng/ml. IRT becomes subnormal in most CF patients by 8 years of age as pancreatic function insufficiency increases. Lipase levels and IRT levels correlate well in infancy, but IRT is a more sensitive indicator of pancreatic insufficiency in older patients with CF.« less

  8. Chronic pancreatitis

    MedlinePlus

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

  9. Pancreatic enzyme replacement therapy.

    PubMed

    Layer, P; Keller, J; Lankisch, P G

    2001-04-01

    Malabsorption due to severe pancreatic exocrine insufficiency is one of the most important late features of chronic pancreatitis. Generally, steatorrhea is more severe and occurs several years prior to malabsorption of other nutrients because synthesis and secretion of lipase are impaired more rapidly, its intraluminal survival is shorter, and the lack of pancreatic lipase activity is not compensated for by nonpancreatic mechanisms. Patients suffer not only from nutritional deficiencies but also from increased nutrient delivery to distal intestinal sites, causing symptoms by profound alteration of upper gastrointestinal secretory and motor functions. Adequate nutrient absorption requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. The following recommendations are based on modern therapeutic concepts: 25,000 to 40,000 units of lipase per meal using pH-sensitive pancreatin microspheres, with dosage increases, compliance checks, and differential diagnosis in case of treatment failure. Still, in most patients, lipid digestion cannot be completely normalized by current standard therapy, and future developments are needed to optimize treatment.

  10. [Industrial application of lipases].

    PubMed

    Bancerz, Renata

    2017-01-01

    The ability of lipases to perform specific reactions of transformation (biotransformation) makes these enzymes a useful tool used in many syntheses, for example: in the production of detergents, cosmetics, biosurfactants, in the oil-chemical, paper, dairy, food or pharmaceutical industries. Lipases are ubiquitous enzymes but only lipases produced by microorganisms are important for industrial applications due to their wide variety of properties such as stability in organic solvents, action under mild conditions, high substrate specificity and region- and enantioselectivity, as well as the relatively simple methods of their production in fermentors and recovery from the culture medium. This paper reviews the latest achievements in the production of lipases in the submerged fermentation and solid state fermentation using waste products from the agricultural industry. In addition, new applications of lipases were described, including those for the synthesis of biopolymers and biodiesel and for the production of enantiomeric pharmaceuticals, agrochemicals and flavoring compounds.

  11. Direct growth-inhibitory effects of prostaglandin E2 in pancreatic cancer cells in vitro through an EP4/PKA-mediated mechanism.

    PubMed

    Schmidt, Andrea; Sinnett-Smith, James; Young, Steven; Chang, Hui-Hua; Hines, O Joe; Dawson, David W; Rozengurt, Enrique; Eibl, Guido

    2017-06-01

    There is strong evidence linking inflammation and the development of pancreatic ductal adenocarcinoma. Cyclooxygenase-2 (COX-2) and COX-2-derived PGE 2 are overexpressed in human and murine pancreatic ductal adenocarcinoma. Several studies have demonstrated an important role of COX-2-derived PGE 2 in tumor-stroma interactions; however, the direct growth effects of prostaglandin E 2 (PGE 2 ) on pancreatic ductal adenocarcinoma cells is less well defined. Our aim was to investigate the effects of PGE 2 on pancreatic ductal adenocarcinoma cell growth and to characterize the underlying mechanisms. Human pancreatic ductal adenocarcinoma cell lines, Panc-1 and MIA PaCa-2, were treated with PGE 2 in varying doses (0-10 μM). Effects on the phosphorylation of ERK1/2 were evaluated by Western blot. Colony formation was observed for cells treated with PGE 2 for 11 days. DNA synthesis was determined by (3H)-thymidine incorporation assay. Gene expression of E-type prostaglandin (EP)2/EP4 receptors and their correlation with survival in patients with pancreatic ductal adenocarcinoma were assessed using the RNA-Seq data set from The Cancer Genome Atlas Research Network. PGE 2 decreased the size and number of colonies in Panc-1 but not MIA PaCa-2 cells. In the Panc-1 cells, PGE 2 activated PKA/CREB and decreased phosphorylation of ERK1/2, which was reversed by an EP4 receptor antagonist, while an EP2 receptor antagonist had no effect. In contrast, in MIA PaCa-2 cells, PGE 2 had no effect on ERK1/2 phosphorylation. Treatment of both Panc-1 and MIA PaCa-2 cells with forskolin/IBMX decreased ERK1/2 phosphorylation. Finally, PGE 2 decreased DNA synthesis only in Panc-1 cells, which was reversed by an EP4 receptor antagonist. In human pancreatic ductal adenocarcinoma, high EP2 and low EP4 gene expression was correlated to worse median overall survival (15.6 vs 20.8 months, log-rank P = .017). Our study provides evidence that PGE 2 can inhibit directly pancreatic ductal

  12. Management of pancreatic exocrine insufficiency: Australasian Pancreatic Club recommendations.

    PubMed

    Toouli, James; Biankin, Andrew V; Oliver, Mark R; Pearce, Callum B; Wilson, Jeremy S; Wray, Nicholas H

    2010-10-18

    Pancreatic exocrine insufficiency (PEI) occurs when the amounts of enzymes secreted into the duodenum in response to a meal are insufficient to maintain normal digestive processes. The main clinical consequence of PEI is fat maldigestion and malabsorption, resulting in steatorrhoea. Pancreatic exocrine function is commonly assessed by conducting a 3-day faecal fat test and by measuring levels of faecal elastase-1 and serum trypsinogen. Pancreatic enzyme replacement therapy is the mainstay of treatment for PEI. In adults, the initial recommended dose of pancreatic enzymes is 25,000 units of lipase per meal, titrating up to a maximum of 80,000 units of lipase per meal. In infants and children, the initial recommended dose of pancreatic enzymes is 500 units of lipase per gram of dietary fat; the maximum daily dose should not exceed 10,000 units of lipase per kilogram of bodyweight. Oral pancreatic enzymes should be taken with meals to ensure adequate mixing with the chyme. Adjunct therapy with acid-suppressing agents may be useful in patients who continue to experience symptoms of PEI despite high-dose enzyme therapy. A dietitian experienced in treating PEI should be involved in patient management. Dietary fat restriction is not recommended for patients with PEI. Patients with PEI should be encouraged to consume small, frequent meals and to abstain from alcohol. Medium-chain triglycerides do not provide any clear nutritional advantage over long-chain triglycerides, but can be trialled in patients who fail to gain or to maintain adequate bodyweight in order to increase energy intake.

  13. Inhibitory Activities of Cyanidin and Its Glycosides and Synergistic Effect with Acarbose against Intestinal α-Glucosidase and Pancreatic α-Amylase

    PubMed Central

    Akkarachiyasit, Sarinya; Charoenlertkul, Piyawan; Yibchok-anun, Sirintorn; Adisakwattana, Sirichai

    2010-01-01

    Cyanidin and its glycosides are naturally dietary pigments which have been indicated as promising candidates to have potential benefits to humans, especially in the prevention and treatment of diabetes mellitus. We investigated the structure activity relationships of cyanidin and its glycosides to inhibit intestinal α-glucosidases and pancreatic α-amylase in vitro. The results found that cyanidin and its glycosides are more specific inhibitors of intestinal sucrase than intestinal maltase. Cyanidin-3-galactoside and cyanidin-3-glucoside were the most potent inhibitors against intestinal sucrase and pancreatic α-amylase with IC50 values of 0.50 ± 0.05 and 0.30 ± 0.01 mM, respectively. Our findings indicate that the structural difference between glucose and galactose at the 3-O-position of cyanidin was an important factor for modulating the inhibition of intestinal sucrase and pancreatic α-amylase. The combination of cyandin-3-glucoside, cyanidin-3- galactoside or cyanidin-3,5-diglucosides with a low concentration of acarbose showed synergistic inhibition on intestinal maltase and sucrase. The synergistic inhibition was also found for a combination of cyanidin or cyanidin-3-glucoside with a low concentration of acarbose. The findings could provide a new insight into a use for the naturally occurring intestinal α-glucosidase and pancreatic α-amylase inhibitors for the prevention and treatment of diabetes and its complications. PMID:20957102

  14. Purtscher's retinopathy that occurred 6 months before acute pancreatitis.

    PubMed

    Sharma, Ashish G; Kazim, Nadia A; Eliott, Dean; Houghton, Odette; Abrams, Gary W

    2006-01-01

    To report Purtscher's retinopathy in a patient with chronic pancreatitis 6 months before the development of fulminant acute pancreatitis. Observational case report. Review of clinical chart, photographs, fluorescein angiography, and optical coherence tomography. A 45-year-old man with a history of alcohol abuse with a 3-day history of decreased vision in both eyes was examined. Diffuse retinal whitening and intraretinal hemorrhages that were consistent with Purtscher's retinopathy were present in both eyes. Serum amylase and lipase levels were normal. Six months later, he experienced intractable abdominal pain. Serum amylase and lipase levels were elevated markedly. Abdominal computed tomography and endoscopic retrograde cholangiopancreatography confirmed acute pancreatitis, with evidence of coexisting chronic pancreatitis. His funduscopic examination after the development of acute pancreatitis was improved, with almost complete resolution of retinal whitening and hemorrhages. Visual acuity remained poor because of retinal ischemia. Purtscher's retinopathy can be associated with chronic pancreatitis and can precede the development of fulminant acute pancreatitis.

  15. Fat digestion by lingual lipase: mechanism of lipolysis in the stomach and upper small intestine.

    PubMed

    Liao, T H; Hamosh, P; Hamosh, M

    1984-05-01

    Ten to 30% of dietary fat is hydrolyzed in the stomach by lingual lipase, an enzyme secreted from lingual serous glands. We investigated the substrate specificity of this enzyme as well as the potential of lingual lipase to act in the upper small intestine i.e., in the presence of bile salts and lecithin. The data presented show that partially purified preparations of rat lingual lipase and the lipase in gastric aspirates of newborn infants have identical substrate specificity: medium-chain triglycerides were hydrolyzed at rates 5-8-fold higher than long-chain triglycerides; the rat and human enzymes do not hydrolyze the ester bond of lecithin or cholesteryl-ester. In contrast to pancreatic lipase, the hydrolysis of triglycerides by lingual lipase is not inhibited by lecithin. But, similar to pancreatic lipase the activity of lingual lipase is inhibited by bile salts, the extent of inhibition varying with its nature and concentration. This inactivation is not prevented by colipase but is partially averted by lipids and protein, suggesting that lingual lipase can remain active in the duodenum. The pH optimum of the enzyme (2.2-6.5 in the rat and 3.5-6.0 in human gastric aspirates) is compatible with continued activity in the upper small intestine, especially during the neonatal period, when the luminal pH is under 6.5. The marked variation in lipase activity levels in gastric aspirates of newborn infants is probably due to individual variations in enzyme amounts. The characteristics of the lipase are however identical in infants with low, intermediate or high activity levels.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Macrophage migration inhibitory factor induces epithelial to mesenchymal transition, enhances tumor aggressiveness and predicts clinical outcome in resected pancreatic ductal adenocarcinoma.

    PubMed

    Funamizu, Naotake; Hu, Chaoxin; Lacy, Curtis; Schetter, Aaron; Zhang, Geng; He, Peijun; Gaedcke, Jochen; Ghadimi, Michael B; Ried, Thomas; Yfantis, Harris G; Lee, Dong H; Subleski, Jeffrey; Chan, Tim; Weiss, Jonathan M; Back, Timothy C; Yanaga, Katsuhiko; Hanna, Nader; Alexander, H Richard; Maitra, Anirban; Hussain, S Perwez

    2013-02-15

    MIF is a proinflammatory cytokine and is implicated in cancer. A higher MIF level is found in many human cancer and cancer-prone inflammatory diseases, including chronic pancreatitis and pancreatic cancer. We tested the hypothesis that MIF contributes to pancreatic cancer aggressiveness and predicts disease outcome in resected cases. Consistent with our hypothesis we found that an elevated MIF mRNA expression in tumors was significantly associated with poor outcome in resected cases. Multivariate Cox-regression analysis further showed that MIF is independently associated with patients' survival (HR = 2.26, 95% CI = 1.17-4.37, p = 0.015). Mechanistic analyses revealed that MIF overexpression decreased E-cadherin and increased vimentin mRNA and protein levels in pancreatic cancer cell lines, consistent with the features of epithelial-to-mesenchymal transition (EMT). Furthermore, MIF-overexpression significantly increased ZEB1/2 and decreased miR-200b expression, while shRNA-mediated inhibition of MIF increased E-cadherin and miR-200b expression, and reduced the expression of ZEB1/2 in Panc1 cells. Re-expression of miR-200b in MIF overexpressing cells restored the epithelial characteristics, as indicated by an increase in E-cadherin and decrease in ZEB1/2 and vimentin expression. A reduced sensitivity to the chemotherapeutic drug, gemcitabine, occurred in MIF-overexpressing cells. Indicative of an increased malignant potential, MIF over-expressing cells showed significant increase in their invasion ability in vitro, and tumor growth and metastasis in an orthotopic xenograft mouse model. These results support a role of MIF in disease aggressiveness, indicating its potential usefulness as a candidate target for designing improved treatment in pancreatic cancer. Copyright © 2012 UICC.

  17. Lipase polystyrene giant amphiphiles.

    PubMed

    Velonia, Kelly; Rowan, Alan E; Nolte, Roeland J M

    2002-04-24

    A new type of giant amphiphilic molecule has been synthesized by covalently connecting a lipase enzyme headgroup to a maleimide-functionalized polystyrene tail (40 repeat units). The resulting biohybrid forms catalytic micellar rods in water.

  18. Protective Effects of Lithospermum erythrorhizon Against Cerulein-Induced Acute Pancreatitis.

    PubMed

    Choi, Sun Bok; Bae, Gi-Sang; Jo, Il-Joo; Seo, Seung-Hee; Kim, Dong-Goo; Shin, Joon-Yeon; Hong, Seung-Heon; Choi, Byung-Min; Park, Sang-Hyun; Song, Ho-Joon; Park, Sung-Joo

    2015-01-01

    We aimed to evaluate the anti-inflammatory and inhibitory effects of Lithospermum erythrorhizon (LE) on cerulein-induced acute pancreatitis (AP) in a mouse model. Acute pancreatitis was induced via intraperitoneal injection of cerulein (50 μg/kg) every hour for 6 times. In the LE, water extract (100, 250, or 500 mg/kg) was administered intraperitoneally 1 hour before the first injection of cerulein. Six hours after AP, blood, the pancreas, and the lung were harvested for further examination. In addition, pancreatic acinar cells were isolated using a collagenase method, and then, we investigated the acinar cell viability and cytokine productions. Treatment with LE reduced pancreatic damage and AP-associated lung injury and attenuated the severity of AP, as evidenced by the reduction in neutrophil infiltration, serum amylase and lipase levels, trypsin activity, and proinflammatory cytokine expression. In addition, treatment with LE inhibited high mobility group box 1 expression in the pancreas during AP. In accordance with in vivo data, LE inhibited the cerulein-induced acinar cell death, cytokine productions, and high-mobility group box 1 expression. Furthermore, LE also inhibited the activation of p38 mitogen-activated protein kinases. These results suggest that LE plays a protective role during the development of AP by inhibiting the activation of p38.

  19. Protective Effects of Lithospermum erythrorhizon Against Cerulein-Induced Acute Pancreatitis

    PubMed Central

    Choi, Sun Bok; Bae, Gi-Sang; Jo, Il-Joo; Seo, Seung-Hee; Kim, Dong-Goo; Shin, Joon-Yeon; Hong, Seung-Heon; Choi, Byung-Min; Park, Sang-Hyun; Song, Ho-Joon; Park, Sung-Joo

    2015-01-01

    Objectives We aimed to evaluate the anti-inflammatory and inhibitory effects of Lithospermum erythrorhizon (LE) on cerulein-induced acute pancreatitis (AP) in a mouse model. Methods Acute pancreatitis was induced via intraperitoneal injection of cerulein (50 μg/kg) every hour for 6 times. In the LE, water extract (100, 250, or 500 mg/kg) was administered intraperitoneally 1 hour before the first injection of cerulein. Six hours after AP, blood, the pancreas, and the lung were harvested for further examination. In addition, pancreatic acinar cells were isolated using a collagenase method, and then, we investigated the acinar cell viability and cytokine productions. Results Treatment with LE reduced pancreatic damage and AP-associated lung injury and attenuated the severity of AP, as evidenced by the reduction in neutrophil infiltration, serum amylase and lipase levels, trypsin activity, and proinflammatory cytokine expression. In addition, treatment with LE inhibited high mobility group box 1 expression in the pancreas during AP. In accordance with in vivo data, LE inhibited the cerulein-induced acinar cell death, cytokine productions, and high-mobility group box 1 expression. Furthermore, LE also inhibited the activation of p38 mitogen-activated protein kinases. Conclusions These results suggest that LE plays a protective role during the development of AP by inhibiting the activation of p38. PMID:25102438

  20. Enhancement of lipase catalyzed-fatty acid methyl esters production from waste activated bleaching earth by nullification of lipase inhibitors.

    PubMed

    Dwiarti, Lies; Ali, Ehsan; Park, Enoch Y

    2010-01-01

    This study sought to identify inhibitory factors of lipase catalyzed-fatty acid methyl esters (FAME) production from waste activated bleaching earth (wABE). During the vegetable oil refinery process, activated bleaching earth (ABE) is used for removing the impure compounds, but adsorbs vegetable oil up to 35-40% as on a weight basis, and then the wABE is discarded as waste material. The impurities were extracted from the wABE with methanol and evaluated by infra-red (IR) spectroscopy, which revealed that some were chlorophyll-plant pigments. The chlorophylls inhibited the lipase during FAME conversion from wABE. The inhibition by a mixture of chlorophyll a and b was found to be competitive. The inhibition of the enzymatic hydrolysis of waste vegetable oil contained in wABE by chlorophyll a alone was competitive, while the inhibition by chlorophyll b alone was non-competitive. Furthermore, the addition of a small amount of alkali nullified this inhibitory effect and accelerated the FAME production rate. When 0.9% KOH (w/w wABE) was added to the transesterification reaction with only 0.05% lipase (w/w wABE), the maximum FAME production rate improved 120-fold, as compared to that without the addition of KOH. The alkali-combined lipase significantly enhanced the FAME production rate from wABE, in spite of the presence of the plant pigments, and even when a lower amount of lipase was used as a catalyst.

  1. Cdk5 inhibitory peptide (CIP) inhibits Cdk5/p25 activity induced by high glucose in pancreatic beta cells and recovers insulin secretion from p25 damage.

    PubMed

    Zheng, Ya-Li; Li, Congyu; Hu, Ya-Fang; Cao, Li; Wang, Hui; Li, Bo; Lu, Xiao-Hua; Bao, Li; Luo, Hong-Yan; Shukla, Varsha; Amin, Niranjana D; Pant, Harish C

    2013-01-01

    Cdk5/p25 hyperactivity has been demonstrated to lead to neuron apoptosis and degenerations. Chronic exposure to high glucose (HG) results in hyperactivity of Cdk5 and reduced insulin secretion. Here, we set out to determine whether abnormal upregulation of Cdk5/p25 activity may be induced in a pancreatic beta cell line, Min6 cells. We first confirmed that p25 were induced in overexpressed p35 cells treated with HG and increased time course dependence. Next, we showed that no p25 was detected under short time HG stimulation (4-12 hrs), however was detectable in the long exposure in HG cells (24 hrs and 48 hrs). Cdk5 activity in the above cells was much higher than low glucose treated cells and resulted in more than 50% inhibition of insulin secretion. We confirmed these results by overexpression of p25 in Min6 cells. As in cortical neurons, CIP, a small peptide, inhibited Cdk5/p25 activity and restored insulin secretion. The same results were detected in co-infection of dominant negative Cdk5 (DNCdk5) with p25. CIP also reduced beta cells apoptosis induced by Cdk5/p25. These studies indicate that Cdk5/p25 hyperactivation deregulates insulin secretion and induces cell death in pancreatic beta cells and suggests that CIP may serve as a therapeutic agent for type 2 diabetes.

  2. Neurotensin modulates the composition of pancreatic exocrine secretions in chickens.

    PubMed

    DeGolier, T F; Place, A R; Duke, G E; Carraway, R E

    The effects of neurotensin on pancreatic exocrine secretion were examined in fasted, conscious White Leghorn hens. A cannula was surgically implanted in the central duct serving the ventral lobe of the pancreas in order to collect pure pancreatic juice. Following recovery, neurotensin was infused intravenously at 3.6 or 10.8 pmol/kg*min. The volume and pH of the pancreatic secretions were recorded and total pancreatic protein concentration, amylase, lipase, trypsin, and chymotrypsin activity were measured every 30 min for 2 hr and compared to secretions following the infusion of 0.9% saline. Our results demonstrated that neurotensin did not affect the pH nor the pancreatic juice protein concentration, but did increase secretion rate following neurotensin infusion at 3.6 pmol/kg*min. Amylase activity was significantly depressed during neurotensin infusions, while lipase (both pancreatic and carboxylester lipase) activity was significantly elevated. The ratio of amylase to lipase activity was especially depressed by neurotensin infusion at 10.8 pmol/kg*min. Insufficient secretory activity prevented a balanced statistical analysis of chymotrypsin activity, but from a pooled analysis, neurotensin had no effect on protease activity in the pancreatic juice. These results support our current research indicating that neurotensin may be a hormonal regulator of postprandial lipid digestion in chickens.

  3. Betaine Attenuates Alcohol-Induced Pancreatic Steatosis.

    PubMed

    Yang, Wenjuan; Gao, Jinhang; Tai, Yang; Chen, Meng; Huang, Luming; Wen, Shilei; Huang, Zhiyin; Liu, Rui; Li, Jing; Tang, Chengwei

    2016-07-01

    To explore the effect of betaine on alcoholic pancreatic steatosis and its mechanism. Rats were randomly assigned to control, ethanol, or ethanol + betaine groups. Changes in pancreatic morphology; serum lipid levels; and pancreatic lipid, amylase and lipase levels were determined. The serum and adipose tissue adiponectin level was measured by an enzyme-linked immunoassay. Adiponectin receptor-1 (AdipoR1), AdipoR2, sterol regulatory element binding protein-1c (SREBP-1c), SREBP-2, and fatty acid synthetase expression levels were quantified. The SREBP-1c expression in SW1990 cells treated with various concentrations of ethanol or ethanol plus betaine and/or adiponectin was assessed. Alcohol-induced changes in pancreatic morphology were attenuated by betaine. Pancreatic triglyceride, free fatty acid and expression levels of SREBP-1c and fatty acid synthetase were elevated after ethanol feeding but remained at control levels after betaine supplementation. Alcohol-induced decreases in serum and adipose tissue adiponectin, pancreatic AdipoR1, amylase, and lipase were attenuated by betaine. Serum triglyceride and free fatty acid levels were elevated after alcohol consumption and remained higher after betaine supplementation compared with controls. Betaine and/or adiponectin suppressed alcohol-induced SREBP-1c upregulation in vitro. Betaine attenuated alcoholic-induced pancreatic steatosis most likely by suppressing pancreatic SREBP-1c both directly and through the restoration of adiponectin signaling.

  4. Chronic Pancreatitis.

    PubMed

    Stram, Michelle; Liu, Shu; Singhi, Aatur D

    2016-12-01

    Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal ("groove") pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Diagnosis and management of pancreatic exocrine insufficiency.

    PubMed

    Nikfarjam, Mehrdad; Wilson, Jeremy S; Smith, Ross C

    2017-08-21

    In 2015, the Australasian Pancreatic Club (APC) published the Australasian guidelines for the management of pancreatic exocrine insufficiency (http://pancreas.org.au/2016/01/pancreatic-exocrine-insufficiency-guidelines). Pancreatic exocrine insufficiency (PEI) occurs when normal digestion cannot be sustained due to insufficient pancreatic digestive enzyme activity. This may be related to a breakdown, at any point, in the pancreatic digestive chain: pancreatic stimulation; synthesis, release or transportation of pancreatic enzymes; or synchronisation of secretions to mix with ingested food. Main recommendations: The guidelines provide advice on diagnosis and management of PEI, noting the following: A high prevalence of PEI is seen in certain diseases and conditions, such as cystic fibrosis, acute and chronic pancreatitis, pancreatic cancer and pancreatic surgery. The main symptoms of PEI are steatorrhoea or diarrhoea, abdominal pain, bloating and weight loss. These symptoms are non-specific and often go undetected and untreated. PEI diagnosis is predominantly based on clinical findings and the presence of underlying disease. The likelihood of PEI in suspected patients has been categorised into three groups: definite, possible and unlikely. If left untreated, PEI may lead to complications related to fat malabsorption and malnutrition, and have an impact on quality of life. Pancreatic enzyme replacement therapy (PERT) remains the mainstay of PEI treatment with the recommended adult initial enzyme dose being 25 000-40 000 units of lipase per meal, titrating up to a maximum of 75 000-80 000 units of lipase per meal. Adjunct acid-suppressing therapy may be useful when patients still experience symptoms of PEI on high dose PERT. Nutritional management by an experienced dietitian is essential. Changes in management as a result of these guidelines: These are the first guidelines to classify PEI as being definite, possible or unlikely, and provide a diagnostic algorithm to

  6. Lipase activity in stallion seminal plasma and the effect of lipase on stallion spermatozoa during storage at 5 degrees C.

    PubMed

    Carver, D A; Ball, B A

    2002-11-01

    Previous studies have demonstrated a detrimental effect of seminal plasma on the maintenance of motility of cooled equine spermatozoa; however, the mechanism for the adverse effect of seminal plasma during cooled storage remains undetermined. In goats, a glycoprotein component of bulbourethral gland secretion contains lipase activity that is detrimental to sperm motility when stored in skim milk-based extenders. The objective of the current study was to determine the amount of lipase activity in stallion seminal plasma and to determine the effect of added lipase on spermatozoal motility during cooled semen storage. In the first experiment, seminal plasma (1.0 ml) was assayed for lipase activity based upon hydrolysis of triglycerides (olive oil substrate) into free fatty acids and subsequent titration of pH change (SigmaDiagnostic Lipase Kit). Lipase activity in stallion seminal plasma was 0.36 +/- 0.02 Sigma units/ml, (mean + S.E.M.; n = 16 ejaculates from six stallions). In the second experiment, equine semen (three ejaculates from each of four stallions) was divided into five treatment aliquots. In Treatment 1, semen was extended 1:3 with nonfat dried skim milk extender (NFDSM). In treatment groups 2 through 5, spermatozoa were washed by centrifugation (300 x g for 15 min) and resuspended in NFDSM to a final concentration of 25 x 10(6) spermatozoa/ml. Porcine pancreatic lipase (pPL) was added to Treatment 3 (10 pPL units/ml), Treatment 4 (100 pPL units/ml) and Treatment 5 (100 pPL units/ml, heat inactivated at 100 degrees C for 5 min) while Treatment 2 had no pancreatic lipase added and served as the control. Samples were cooled slowly to 5 degrees C, and stored at 5 degrees C until evaluation. Sperm motility was evaluated at time 0, 24, 48 and 72 h by computerized semen analysis, and data were analyzed via repeated measures ANOVA. The addition of 100 units/ml but not 10 units/ml of pPL decreased (P < 0.01) total and progressive motility of stored sperm. Heat

  7. Microwave assisted synthesis and anti-lipase activity of some new fluorine-containing benzimidazoles.

    PubMed

    Menteşe, E; Yilmaz, F; Ülker, S; Kahveci, B

    2015-01-01

    In this study, a new series of fluorine containing benzimidazoles (4a-l) and bisbenzimidazoles (6a-c, 8) were synthesized by the reaction of o-phenylenediamines with iminoester hydrochlorides (3a-l, 7) in methanol under microwave irradiation. The structures of these newly synthesized compounds were identified by IR, (1)H-NMR, (13)C-NMR, mass spectroscopy and elemental analysis data. The synthesized compounds were screened for their pancreatic lipase activities. Our results indicate that the compounds 6a, 6b and 6c can serve as an anti-lipase agent. The compounds 6b and 6c inhibited pancreatic lipase activity by 84.03% and 97.49% at a concentration of 3 µg/mL, respectively. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Polyarthritis and bone lesions complicating traumatic pancreatitis in two children.

    PubMed Central

    Goluboff, N.; Cram, R.; Ramgotra, B.; Singh, A.; Wilkinson, G. W.

    1978-01-01

    The association of bone lesions, polyarthritis and cutaneous nodules with pancreatic disease is being recognized and reported more frequently. In adults all forms of pancreatitis and carcinoma of the pancreas have been involved, but in the few children described these complications have been associated with acute traumatic pancreatitis. This paper describes two cases of acute traumatic pancreatitis in which polyarthritis and limb pains were noted after 2 to 3 weeks. In one child osteolytic lesions and periostitis were seen on roentgenograms 7 weeks after the onset of pancreatitis. In the other child minor roentgenographic changes were not seen until 5 months after the onset; however, bone scans showed clear-cut abnormalities after 1 month. Almost complete resolution could be expected within a year. Serum lipase and amylase concentrations remained elevated during the acute illness. Disseminated fat necrosis is apparently related to the excess amounts of circulating lipase. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 PMID:647564

  9. Involvement of the cGMP pathway in mediating the insulin-inhibitory effect of melatonin in pancreatic beta-cells.

    PubMed

    Stumpf, Ina; Mühlbauer, Eckhard; Peschke, Elmar

    2008-10-01

    Recent investigations have demonstrated an influence of melatonin on insulin secretion in pancreatic beta-cells. The effects are receptor-mediated via two parallel signaling pathways. The aim of this study was to examine the relevance of a second melatonin receptor (MT2) as well as the involvement of a third signaling cascade in mediating melatonin effects, i.e. the cyclic guanosine monophosphate (cGMP) pathway. Our results demonstrate that the insulin-inhibiting effect of melatonin could be partly reversed by preincubation with the unspecific melatonin receptor antagonist luzindole as well as by the MT2-receptor-specific antagonist 4P-PDOT (4-phenyl-2-propionamidotetraline). As melatonin is known to modulate cGMP concentration via the MT2 receptor, these data indicate transmission of the melatonin effects via the cGMP transduction cascade. Molecular investigations established the presence of different types of guanylate cyclases, cGMP-specific phosphodiesterases and cyclic nucleotide-gated channels in rat insulinoma beta-cells (INS1). Moreover, variations in mRNA expression were found when comparing day and night values as well as different states of glucose metabolism. Incubation experiments provided evidence that 3-isobutyl-1-methylxanthine (IBMX)-stimulated cGMP concentrations were significantly decreased in INS1 cells exposed to melatonin for 1 hr in a dose- and time-dependent manner. This effect could also be reversed by application of luzindole and 4P-PDOT. Stimulation with 8-Br-cGMP resulted in significantly increased insulin production. In conclusion, it could be demonstrated that the melatonin receptor subtype MT2 as well as the cGMP signaling pathway are involved in mediating the insulin-inhibiting effect of melatonin.

  10. Serum Lipase as Clinical Laboratory Index for Chronic Renal Failure Diagnosis.

    PubMed

    Zhu, Ying; Dong, Jing; Wang, Ping; Huang, Huifang; Jin, Xiaohua; Zhou, Jingou; Shi, Jingfang; Gu, Guohao; Chen, Jun; Xu, Jun; Song, Yanhui

    2016-07-01

    Measuring the level of serum lipase has been used for the clinical diagnosis of acute pancreatitis. Reports showed that the serum lipase level increased in patients of clinical renal failure. In this study, we aimed to measure the change of serum lipase levels in chronic kidney diseases and determine whether it could serve as a clinical laboratory index for clinical renal failure diagnosis. Materials: The OLYMPUS AU5400 automatic biochemical analyzer was used to determine the serum levels of lipase and creatinine. The study included 120 cases in the clinical renal failure group, 76 cases in the nephrotic syndrome group, 81 cases in the chronic nephritis group, and 80 healthy controls from our hospital volunteers in the same period. We then compared the lipase levels and conducted statistical analyses among these groups. The serum lipase levels were 15.3 U/L, 79.8 U/L, 45.1 U/L, and 51.0 U/L in the normal control, clinical renal failure, nephrotic syndrome, and chronic nephritis groups, respectively. The lipase levels in the groups with diseases were significantly different compared with that of the normal control group (p < 0.01). The lipase level of the clinical renal failure group was significantly higher than that of the nephrotic syndrome group and chronic nephritis group (p < 0.01). However, no statistically significant difference between the nephrotic syndrome and chronic nephritis group (p > 0.05) was observed. Moreover, an association of the serum lipase with disease progression was observed in the study. Serum lipase is an effective serological index which can reflect the clinical changes in the clinical renal failure and tends to increase through the progression of renal dysfunction.

  11. Pancreatic Cysts

    MedlinePlus

    ... enzymes become prematurely active and irritate the pancreas (pancreatitis). Pseudocysts can also result from injury to the ... alcohol use and gallstones are risk factors for pancreatitis, and pancreatitis is a risk factor for pseudocysts. ...

  12. Pancreatic Cancer

    MedlinePlus

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

  13. Inhibitory potentials of phenolic-rich extracts from Bridelia ferruginea on two key carbohydrate-metabolizing enzymes and Fe2+-induced pancreatic oxidative stress.

    PubMed

    Afolabi, Olakunle Bamikole; Oloyede, Omotade Ibidun; Agunbiade, Shadrack Oludare

    2018-05-01

    The current study was designed to evaluate the various antioxidant potentials and inhibitory effects of phenolic-rich leaf extracts of Bridelia ferruginea (BF) on the in vitro activities of some key enzymes involved in the metabolism of carbohydrates. In this study, BF leaf free and bound phenolic-rich extracts were used. We quantified total phenolic and flavonoid contents, and evaluated several antioxidant activities using assays for ferric reducing antioxidant power, total antioxidant activity (phosphomolybdenum reducing ability), 1,1-diphenyl-2-picrylhydrazyl and thiobarbituric acid reactive species. Also, extracts were tested for their ability to inhibit α-amylase and α-glucosidase activity. The total phenolic and total flavonoid contents in the free phenolic extract of BF were significantly greater than in the bound phenolic extract. Also, all the antioxidant activities considered were significantly greater in the free phenolic extract than in the bound phenolic extract. In the same vein, the free phenolic-rich extract had a significantly higher percentage inhibition against α-glucosidase activity (IC 50  = 28.5 µg/mL) than the bound phenolic extract (IC 50  = 340.0 µg/mL). On the contrary, the free phenolic extract (IC 50  = 210.0 µg/mL) had significantly lower inhibition against α-amylase than the bound phenolic-rich extract (IC 50  = 190.0 µg/mL). The phenolic-rich extracts of BF leaves showed antioxidant potentials and inhibited two key carbohydrate-metabolizing enzymes in vitro. Copyright © 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

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

    PubMed

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

    1998-05-01

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

  15. Exploring the specific features of interfacial enzymology based on lipase studies.

    PubMed

    Aloulou, Ahmed; Rodriguez, Jorge A; Fernandez, Sylvie; van Oosterhout, Dirk; Puccinelli, Delphine; Carrière, Frédéric

    2006-09-01

    Many enzymes are active at interfaces in the living world (such as in the signaling processes at the surface of cell membranes, digestion of dietary lipids, starch and cellulose degradation, etc.), but fundamental enzymology remains largely focused on the interactions between enzymes and soluble substrates. The biochemical and kinetic characterization of lipolytic enzymes has opened up new paths of research in the field of interfacial enzymology. Lipases are water-soluble enzymes hydrolyzing insoluble triglyceride substrates, and studies on these enzymes have led to the development of specific interfacial kinetic models. Structure-function studies on lipases have thrown light on the interfacial recognition sites present in the molecular structure of these enzymes, the conformational changes occurring in the presence of lipids and amphiphiles, and the stability of the enzymes present at interfaces. The pH-dependent activity, substrate specificity and inhibition of these enzymes can all result from both "classical" interactions between a substrate or inhibitor and the active site, as well as from the adsorption of the enzymes at the surface of aggregated substrate particles such as oil drops, lipid bilayers or monomolecular lipid films. The adsorption step can provide an alternative target for improving substrate specificity and developing specific enzyme inhibitors. Several data obtained with gastric lipase, classical pancreatic lipase, pancreatic lipase-related protein 2 and phosphatidylserine-specific phospholipase A1 were chosen here to illustrate these specific features of interfacial enzymology.

  16. Ethanol Administration Impairs Pancreatic Repair Following Injury

    PubMed Central

    Mahan Schneider, Katrina J.; Scheer, Marc; Suhr, Mallory; Clemens, Dahn L.

    2012-01-01

    Objectives Alcohol abuse is one of the most common factors associated with acute and chronic pancreatitis. Although it is evident that alcohol abuse can have an important role in the development of pancreatitis, it does not appear that alcohol abuse alone is responsible for this disease. We investigated the involvement of ethanol in impairment of pancreatic repair after induction of pancreatitis. Methods A biologically relevant mouse model of alcoholic pancreatitis, combining chronic ethanol consumption and coxsackievirus infection, was used to investigate the effects of ethanol on pancreatic regeneration. Tissues were harvested and analyzed by RT-PCR and immunoblot. Results These studies demonstrate that chronic ethanol consumption impairs the structural repair of the exocrine pancreas. This is accompanied by a delay in the restitution of lipase expression. Additionally, impaired expression of the critical pancreatic transcription factors, PDX1 and PTF1, and the mediator of Notch signaling, HES1, were observed. Conclusions Chronic ethanol consumption impairs the structural repair and functional restitution of the pancreas after severe injury. These impairments may, in part, be explained by impaired expression of factors important in the development and maintenance of the exocrine pancreas. Impaired pancreatic regeneration may have a role in the pathogenesis of alcoholic pancreatitis. PMID:22617711

  17. Lipolysis of the semi-solid self-emulsifying excipient Gelucire 44/14 by digestive lipases.

    PubMed

    Fernandez, Sylvie; Rodier, Jean-David; Ritter, Nicolas; Mahler, Bruno; Demarne, Frédéric; Carrière, Frédéric; Jannin, Vincent

    2008-08-01

    Gelucire 44/14 is a semi-solid self-emulsifying excipient used for the oral delivery of poorly water-soluble drugs. It is composed of C8-C18 acylglycerols and PEG-32 esters, all of which are potential substrates for digestive lipases. Here we studied the lipolysis of Gelucire 44/14 by porcine pancreatic extracts, human pancreatic juice and several purified digestive lipases. Human pancreatic lipase (HPL), the main lipase involved in the digestion of triacylglycerols, did not show any significant activity on Gelucire 44/14 or on either of its individual compounds, C8-C18 acylglycerols and PEG-32 esters. Other pancreatic lipases such as human pancreatic lipase-related protein 2 (HPLRP2) showed low activity on Gelucire 44/14 although the highest activity of HPLRP2 was that observed on the C8-C18 acylglycerol fraction, which accounts for 20% (w/w) of Gelucire 44/14. In addition, HPLRP2 showed low activities on the PEG-32 esters, whether these were tested individually or mixed together. Carboxyl ester hydrolase (CEH) showed high activity on Gelucire 44/14, and the highest activities of CEH were those recorded on the total PEG-32 ester fraction and on each individual PEG-32 ester, except for PEG-32 monostearate. The highest activity of all the enzymes tested was that of dog gastric lipase (DGL) on Gelucire 44/14, although DGL showed low activity on the PEG-32 ester fraction and on each individual PEG-32 ester. We compared the lipolysis of Gelucire 44/14 with that of Labrasol, another self-emulsifying excipient, which is liquid at room temperature. Human pancreatic juice showed similar rates of activity on both Gelucire 44/14 and Labrasol. This finding means that these excipients are hydrolyzed in vivo during pancreatic digestion, mainly by CEH in the case of Gelucire 44/14 and by both HPLRP2 and CEH in that of Labrasol, whereas HPL showed very low activities on each of these two excipients. This is the first time the effects of PEG and acyl chain length on the lipolytic

  18. Development of a high-throughput assay for measuring lipase activity using natural triacylglycerols coated on microtiter plates.

    PubMed

    Serveau-Avesque, Carole; Verger, Robert; Rodriguez, Jorge A; Abousalham, Abdelkarim

    2013-09-21

    We have designed a convenient, specific, sensitive and continuous lipase assay based on the use of natural triacylglycerols (TAGs) from the Aleurites fordii seed oil which contains α-eleostearic acid (9,11,13,cis,trans,trans-octadecatrienoic acid) and which was coated in the wells of microtiter plates. The coated TAG film cannot be desorbed by the various buffers used during the lipase assay. Upon lipase action, α-eleostearic acid is liberated and desorbed from the interface and then solubilized into the micellar phase. Consequently, the UV absorbance of the α-eleostearic acid is considerably enhanced due to the transformation from an adsorbed to a water soluble state. The lipase activity can be measured continuously by recording the variations with time of the UV absorption spectra. The rate of lipolysis was monitored by measuring the increase of OD at 272 nm, which was found to be linear with time and directly proportional to the amount of added lipase. This microtiter plate lipase assay, based on coated TAGs, presents various advantages as compared to the classical systems: (i) coated TAGs on the microtiter plates could be stored for a long-time at 4 °C, (ii) higher sensitivity in lipase detection, (iii) good reproducibility, and (iv) increase of signal to noise ratio due to high UV absorption after transfer of α-eleostearic acid from an adsorbed to a soluble state. Low concentrations, down to 1 pg mL(-1) of pure Thermomyces lanuginosus or human pancreatic lipase, could be detected under standard assay conditions. The detection sensitivity of this coated method is around 1000 times higher as compared to those obtained with the classical emulsified systems. This continuous high throughput lipase assay could be used to screen new lipases and/or lipase inhibitors present in various biological samples.

  19. Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

    PubMed Central

    Noel, Pawan; Patel, Krutika; Durgampudi, Chandra; Trivedi, Ram N; de Oliveira, Cristiane; Crowell, Michael D; Pannala, Rahul; Lee, Kenneth; Brand, Randall; Chennat, Jennifer; Slivka, Adam; Papachristou, Georgios I; Khalid, Asif; Whitcomb, David C; DeLany, James P; Cline, Rachel A; Acharya, Chathur; Jaligama, Deepthi; Murad, Faris M; Yadav, Dhiraj; Navina, Sarah; Singh, Vijay P

    2016-01-01

    Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP. PMID:25500204

  20. Biodiesel production with immobilized lipase: A review.

    PubMed

    Tan, Tianwei; Lu, Jike; Nie, Kaili; Deng, Li; Wang, Fang

    2010-01-01

    Fatty acid alkyl esters, also called biodiesel, are environmentally friendly and show great potential as an alternative liquid fuel. Biodiesel is produced by transesterification of oils or fats with chemical catalysts or lipase. Immobilized lipase as the biocatalyst draws high attention because that process is "greener". This article reviews the current status of biodiesel production with immobilized lipase, including various lipases, immobilization methods, various feedstocks, lipase inactivation caused by short chain alcohols and large scale industrialization. Adsorption is still the most widely employed method for lipase immobilization. There are two kinds of lipase used most frequently especially for large scale industrialization. One is Candida antartica lipase immobilized on acrylic resin, and the other is Candida sp. 99-125 lipase immobilized on inexpensive textile membranes. However, to further reduce the cost of biodiesel production, new immobilization techniques with higher activity and stability still need to be explored. Copyright 2010 Elsevier Inc. All rights reserved.

  1. 21 CFR 862.1465 - Lipase test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Lipase test system. (a) Identification. A lipase test system is a device intended to measure the activity of the enzymes lipase in serum. Lipase measurements are used in diagnosis and treatment of diseases...

  2. 21 CFR 862.1465 - Lipase test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Lipase test system. (a) Identification. A lipase test system is a device intended to measure the activity of the enzymes lipase in serum. Lipase measurements are used in diagnosis and treatment of diseases...

  3. Lipases in Medicine: An Overview.

    PubMed

    Loli, Heni; Narwal, Sunil Kumar; Saun, Nitin Kumar; Gupta, Reena

    2015-01-01

    Lipases are part of the family of hydrolases that act on carboxylic ester bonds. They are involved in catalyzing the hydrolysis of triglycerides (TG) into chylomicrons and very low density lipoprotein (VLDL) particles. Uses of lipases are evolving rapidly and currently they are reported to show high potential in medicine. Intensive study and investigations have led researchers to explore lipases for their use in substitution therapy, where in enzyme deficiency during diseased conditions is compensated by their external administration. In our body, they are used to break down fats present in food so that they can be absorbed in the intestine and deficiency of lipases leads to malabsorption of fats and fat-soluble vitamins. Lipases help a person who has cystic fibrosis, Alzheimer's disease, atherosclerosis and act as a candidate target for cancer prevention and therapy. They act as diagnostic tool and their presence or increasing levels can indicate certain infection or disease. Obesity causes metabolic disease and is a serious health problem around the world. Thus inhibiting digestive lipase to reduce fat absorption has become the main pharmacological approach to the treatment of obesity in recent years.

  4. Pancreatic rupture in four cats with high-rise syndrome.

    PubMed

    Liehmann, Lea M; Dörner, Judith; Hittmair, Katharina M; Schwendenwein, Ilse; Reifinger, Martin; Dupré, Gilles

    2012-02-01

    Pancreatic trauma and rupture are rare after feline high-rise syndrome; however, should it happen, pancreatic enzymes will leak into the abdominal cavity and may cause pancreatic autodigestion and fatty tissue saponification. If not diagnosed and treated, it can ultimately lead to multiorgan failure and death. In this case series, 700 records of high-rise syndrome cats that presented between April 2001 and May 2006 were analysed, and four cats with pancreatic rupture were identified. Clinical signs, diagnosis using ultrasonography and lipase activity in blood and abdominal effusion, and treatment modalities are reported. Three cats underwent surgical abdominal exploration, one cat was euthanased. Rupture of the left pancreatic limb was confirmed in all cases. Two of the operated cats survived to date. High-rise syndrome can lead to abdominal trauma, including pancreatic rupture. A prompt diagnosis and surgical treatment should be considered.

  5. Effects of Erdosteine on Experimental Acute Pancreatitis Model.

    PubMed

    Karapolat, Banu; Karapolat, Sami; Gurleyik, Emin; Yasar, Mehmet

    2017-10-01

    To create acute pancreatitis condition experimentally in rats using cerulein, and to reveal histopathological effects in pancreatic tissue with erdosteine. An experimental study. Department of General Surgery, Duzce University, Turkey, from June to October 2014. Thirty male Wistar albino rats were divided into three groups. No procedures were applied to Group 1. The rats in Group 2 and Group 3 were injected cerulein, to establish an experimental pancreatitis model and the blood amylase and lipase values were examined. The rats in Group 3 were given 10 mg/kg erdosteine. This treatment was continued for another 2 days and the rats were sacrificed. The pancreatic tissues were examined histopathologically for edema, inflammation, acinar necrosis, fat necrosis, and vacuolization. The lipase and amylase values and the histopathological examination of pancreatic tissues evidenced that the experimental acute pancreatitis model was established and edema, inflammation, acinar necrosis, fat necrosis, and vacuolization were observed in the pancreatic tissues. The statistical results suggest that erdosteine can decrease the edema, inflammation, acinar necrosis, fat necrosis and vacuolization scores in the tissues. The severity of acute pancreatitis, induced by cerulein in rats, is reduced with the use of erdosteine.

  6. Pancreatic Enzymes

    MedlinePlus

    ... Contributions to the Pancreatic Cancer Action Network are tax-deductible to the extent permitted by law. The Pancreatic Cancer Action Network’s tax identification number is #33-0841281. Our 13th Consecutive ...

  7. Acute pancreatitis

    MedlinePlus

    ... that lead to high blood levels of triglycerides. Alternative Names Gallstone pancreatitis; Pancreas - inflammation Patient Instructions Pancreatitis - ... any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should ...

  8. Acetylsalicylic acid (aspirin) reduces damage to reconstituted human tissues infected with Candida species by inhibiting extracellular fungal lipases

    PubMed Central

    Trofa, David; Agovino, Mariangela; Stehr, Frank; Schäfer, Wilhelm; Rykunov, Dmitry; Fiser, András; Hamari, Zsuzsanna; Nosanchuk, Joshua D.; Gácser, Attila

    2009-01-01

    A reconstituted human tissue model was used to mimic Candida albicans and Candida parapsilosis infection in order to investigate the protective effects of acetylsalicylic acid (aspirin, ASA). We found that therapeutic concentrations of ASA reduced tissue damage in the in vitro infection model. We further evaluated the lipase inhibitory effects of ASA by investigating the growth of C. albicans, C. parapsilosis and C. parapsilosis lipase negative (Δcplip1-2/Δcplip1-2) mutants in a lipid rich minimal medium supplemented with olive oil and found that a therapeutic concentration of ASA inhibited the growth of wild type fungi. The lipase inhibitors quinine and ebelactone B were also shown to reduce growth and protect against tissue damage from Candida species, respectively. A lipolytic activity assay also showed that therapeutic concentrations of ASA inhibited C. antarctica and C. cylindracea purified lipases obtained through a commercial kit. The relationship between ASA and lipase was characterized through a computed structural model of the Lipase-2 protein from C. parapsilosis in complex with ASA. The results suggest that development of inhibitors of fungal lipases could result in broad-spectrum therapeutics, especially since fungal lipases are not homologous to their human analogues. PMID:19703582

  9. Inhibitory Activities of Zygophyllum album: A Natural Weight-Lowering Plant on Key Enzymes in High-Fat Diet-Fed Rats

    PubMed Central

    Mnafgui, Kais; Hamden, Khaled; Ben Salah, Hichem; Kchaou, Mouna; Nasri, Mbarek; Slama, Sadok; Derbali, Fatma; Allouche, Noureddine; Elfeki, Abdelfattah

    2012-01-01

    Obesity is a serious health problem that increased risk for many complications, including diabetes and cardiovascular disease. The results showed EZA, which found rich in flavonoids and phenolic compounds, exhibited an inhibitory activity on pancreatic lipase in vitro with IC50 of 91.07 μg/mL. In vivo administration of this extract to HFD-rats lowered body weight and serum leptin level; and inhibited lipase activity of obese rats by 37% leading to notable decrease of T-Ch, TGs and LDL-c levels accompanied with an increase in HDL-c concentration in serum and liver of EZA treated HFD-rats. Moreover, the findings revealed that EZA helped to protect liver tissue from the appearance of fatty cysts. Interestingly, supplementation of EZA modulated key enzyme related to hypertension such as ACE by 36% in serum of HFD animals and improve some of serum electrolytes such as Na+, K+, Cl−, Ca2+ and Mg2+. Moreover, EZA significantly protected the liver-kidney function by reverted back near to normal the values of the liver-kidney dysfunction indices AST&ALT, ALP, CPK and GGT activities, decreased T-Bili, creat, urea and uric acid rates. In conclusion, these results showed a strong antihypelipidemic effect of EZA which can delay the occurrence of dislipidemia and hypertension. PMID:23258993

  10. In vitro inhibitory potential of Cynara scolymus, Silybum marianum, Taraxacum officinale, and Peumus boldus on key enzymes relevant to metabolic syndrome.

    PubMed

    Villiger, Angela; Sala, Filippo; Suter, Andy; Butterweck, Veronika

    2015-01-15

    Boldocynara®, a proprietary dietary supplement product consisting of the plants Cynara scolymus, Silybum marianum, Taraxacum officinale, and Peumus boldus, used to promote functions of the liver and the gallbladder. It was the aim of the present study to look from a different perspective at the product by investigating the in vitro potential of Boldocynara® as a combination product and its individual extracts on key enzymes relevant to metabolic syndrome. Peumus boldus extract exhibited pronounced inhibitory activities on α-glucosidase (80% inhibition at 100 µg/ml, IC50: 17.56 µg/ml). Silybum marianum had moderate pancreatic lipase (PL) inhibitory activities (30% at 100 µg/ml) whereas Cynara scolymus showed moderate ACE inhibitory activity (31% at 100 µg/ml). The combination had moderate to weak effects on the tested enzymes. In conclusion, our results indicate some moderate potential of the dietary supplement Boldocynara® and its single ingredients for the prevention of metabolic disorders. Copyright © 2014 Elsevier GmbH. All rights reserved.

  11. α-Eleostearic acid-containing triglycerides for a continuous assay to determine lipase sn-1 and sn-3 regio-preference.

    PubMed

    El Alaoui, Meddy; Soulère, Laurent; Noiriel, Alexandre; Queneau, Yves; Abousalham, Abdelkarim

    2017-08-01

    Lipases are essentially described as sn-1 and sn-3 regio-selective. Actually few methods are available to measure this lipase regio-selectivity, moreover they require chiral chromatography analysis or specific derivations which are discontinuous and time consuming. In this study we describe a new, convenient, sensitive and continuous spectrophotometric method to screen lipases regio-selectivity using synthetic triglycerides (TG) containing α-eleostearic acid (9Z, 11E, 13E-octadecatrienoic acid) either at the sn-1 position [1-α-eleostearoyl-2,3-octadecyl-sn-glycerol (sn-EOO)] or at the sn-3 position [1,2-octadecyl-3-α-eleostearoyl-sn-glycerol (sn-OOE)] and coated onto the wells of microtiter plates. A non-hydrolysable ether bond, with a non UV-absorbing alkyl chain, was introduced at the other sn positions to prevent acyl chain migration during TG synthesis or lipolysis. The synthesis of TG containing α-eleostearic acid was performed from S-glycidol in six steps to obtain sn-EOO and in five steps to sn-OOE. The α-eleostearic acid conjugated triene constitutes an intrinsic chromophore and, consequently, confers the strong UV absorption properties of this free fatty acid as well as of the TG harboring it. The lipase activity on coated sn-EOO or sn-OOE was measured by the increase in the absorbance at 272nm due to the transition of α-eleostearic acid from the adsorbed to the soluble state. Human and porcine pancreatic lipases, guinea pig pancreatic lipase related protein 2, Thermomyces lanuginosus lipase, Candida antarctica lipase A and Candida antarctica lipase B were all used to validate the assay. This continuous high-throughput screening method could determine directly without any processes after lipolysis the regio-selectivity of various lipases. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Abdominal pain and hyperamylasaemia—not always pancreatitis

    PubMed Central

    Slack, Sally; Abbey, Ianthe; Smith, Dominic

    2010-01-01

    A raised serum amylase concentration, at least four times the upper limit of normal (ULN), is used to support the diagnosis of acute pancreatitis in a patient presenting with abdominal pain. The authors report a case of toxic shock syndrome complicated by a raised serum amylase concentration that peaked at 50 times the ULN in a patient with recurrent abdominal pain. The commonest cause of hyperamylasaemia is pancreatic; however, further investigation of serum lipase and amylase isoenzyme studies found this to be of salivary origin and attributable to soft tissue inflammation of the salivary gland. This case highlights the need to consider non-pancreatic causes of hyperamylasaemia. PMID:22767564

  13. Abdominal pain and hyperamylasaemia--not always pancreatitis.

    PubMed

    Slack, Sally; Abbey, Ianthe; Smith, Dominic

    2010-07-21

    A raised serum amylase concentration, at least four times the upper limit of normal (ULN), is used to support the diagnosis of acute pancreatitis in a patient presenting with abdominal pain. The authors report a case of toxic shock syndrome complicated by a raised serum amylase concentration that peaked at 50 times the ULN in a patient with recurrent abdominal pain. The commonest cause of hyperamylasaemia is pancreatic; however, further investigation of serum lipase and amylase isoenzyme studies found this to be of salivary origin and attributable to soft tissue inflammation of the salivary gland. This case highlights the need to consider non-pancreatic causes of hyperamylasaemia.

  14. Impact of lipases on the protective effect of SEDDS for incorporated peptide drugs towards intestinal peptidases.

    PubMed

    Leonaviciute, Gintare; Zupančič, Ožbej; Prüfert, Felix; Rohrer, Julia; Bernkop-Schnürch, Andreas

    2016-07-11

    The aim of this study is the development of self-emulsifying drug delivery systems (SEDDS) differing in amounts of ester substructures and to evaluate their stability in presence of pancreatic lipase and protective effect against luminal enzymatic metabolism using leuprorelin as model peptide drug. Hydrophobic leuprolide oleate was incorporated into three different SEDDS formulations and their stability towards pancreatic lipases was investigated utilizing a dynamic in vitro digestion model. Protective effect of SEDDS in respect to peptide drug stability against proteolytic enzymes, trypsin and α-chymotrypsin, was determined via HPLC. Results of in vitro digestion demonstrated that 80% of SEDDS containing the highest amount of ester linkages was degraded within 60min. In comparison to that, SEDDS without ester bonds showed no degradation. With increasing oil droplets hydrolysis the remaining amount of peptide encapsulated into formulation decreased. Furthermore, after 180min incubation with trypsin up to 33.5% and with α-chymotrypsin up to 60.5% of leuprolide oleate was intact while leuprorelin acetate aqueous solution was completely metabolized by trypsin within 120min and by α-chymotrypsin within 5min. Protective effect in environment containing lipases was lower due to oil phase degradation, however, the amount of peptide in ester-free SEDDS was remarkably higher compared to SEDDS susceptible to lipases. The present study revealed that SEDDS stable towards hydrolysis is able to exhibit a protective effect for oral peptide delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Pancreatic Cancer

    PubMed Central

    Maitra, Anirban; Hruban, Ralph H.

    2009-01-01

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

  16. Duodenal Loop Obstruction as an Unusual Cause of Acute Pancreatitis: A Case Series.

    PubMed

    Lee, Hyeonmin; Choi, Yonghyeok; Jeong, Hyewon; Lim, Jae Kyu; Jung, Taeyoung; Han, Joung Ho; Park, Seon Mee

    2016-12-25

    Duodenal loop obstruction is an unusual cause of acute pancreatitis. Increased intraluminal pressure hinders pancreatic flow, causing dilatation of the pancreatic duct and inducing acute pancreatitis. We experienced three cases of acute pancreatitis that resulted from duodenal loop obstruction after (1) an esophagectomy with gastric pull-up procedure for esophageal cancer, (2) a gastrectomy with Billroth I reconstruction for gastric cancer, and (3) a gastrojejunostomy for abdominal trauma. An abdominal CT scan revealed a distended duodenal loop, dilated pancreatic duct, and inflamed pancreas with fluid collection. Acute pancreatitis with duodenal loop obstruction was diagnosed by abdominal pain, elevated serum amylase/lipase, and abdominal CT findings. Immediate decompression with a nasogastric tube was performed, and all patients showed improvement within one week after admission. Each patient was followed up for more than two years without recurrence. Our findings suggest the usefulness of nasogastric tube decompression as the first line of treatment for acute pancreatitis related to duodenal loop obstruction.

  17. Biodegradable products by lipase biocatalysis.

    PubMed

    Linko, Y Y; Lämsä, M; Wu, X; Uosukainen, E; Seppälä, J; Linko, P

    1998-11-18

    The interest in the applications of biocatalysis in organic syntheses has rapidly increased. In this context, lipases have recently become one of the most studied groups of enzymes. We have demonstrated that lipases can be used as biocatalyst in the production of useful biodegradable compounds. A number of examples are given. 1-Butyl oleate was produced by direct esterification of butanol and oleic acid to decrease the viscosity of biodiesel in winter use. Enzymic alcoholysis of vegetable oils without additional organic solvent has been little investigated. We have shown that a mixture of 2-ethyl-1-hexyl esters can be obtained in a good yield by enzymic transesterification from rapeseed oil fatty acids for use as a solvent. Trimethylolpropane esters were also similarly synthesized as lubricants. Finally, the discovery that lipases can also catalyze ester syntheses and transesterification reactions in organic solvent systems has opened up the possibility of enzyme catalyzed production of biodegradable polyesters. In direct polyesterification of 1,4-butanediol and sebacic acid, polyesters with a mass average molar mass of the order of 56,000 g mol-1 or higher, and a maximum molar mass of about 130,000 g mol-1 were also obtained by using lipase as biocatalyst. Finally, we have demonstrated that also aromatic polyesters can be synthesized by lipase biocatalysis, a higher than 50,000 g mol-1 mass average molar mass of poly(1,6-hexanediyl isophthalate) as an example.

  18. Pancreatic trauma

    PubMed Central

    Bhattacharya, S

    2013-01-01

    Introduction Pancreatic trauma occurs in approximately 4% of all patients sustaining abdominal injuries. The pancreas has an intimate relationship with the major upper abdominal vessels, and there is significant morbidity and mortality associated with severe pancreatic injury. Immediate resuscitation and investigations are essential to delineate the nature of the injury, and to plan further management. If main pancreatic duct injuries are identified, specialised input from a tertiary hepatopancreaticobiliary (HPB) team is advised. Methods A comprehensive online literature search was performed using PubMed. Relevant articles from international journals were selected. The search terms used were: ‘pancreatic trauma’, ‘pancreatic duct injury’, ‘radiology AND pancreas injury’, ‘diagnosis of pancreatic trauma’, and ‘management AND surgery’. Articles that were not published in English were excluded. All articles used were selected on relevance to this review and read by both authors. Results Pancreatic trauma is rare and associated with injury to other upper abdominal viscera. Patients present with non-specific abdominal findings and serum amylase is of little use in diagnosis. Computed tomography is effective in diagnosing pancreatic injury but not duct disruption, which is most easily seen on endoscopic retrograde cholangiopancreaticography or operative pancreatography. If pancreatic injury is suspected, inspection of the entire pancreas and duodenum is required to ensure full evaluation at laparotomy. The operative management of pancreatic injury depends on the grade of injury found at laparotomy. The most important prognostic factor is main duct disruption and, if found, reconstructive options should be determined by an experienced HPB surgeon. Conclusions The diagnosis of pancreatic trauma requires a high index of suspicion and detailed imaging studies. Grading pancreatic injury is important to guide operative management. The most important

  19. Pancreatic trauma.

    PubMed

    Lahiri, R; Bhattacharya, S

    2013-05-01

    Pancreatic trauma occurs in approximately 4% of all patients sustaining abdominal injuries. The pancreas has an intimate relationship with the major upper abdominal vessels, and there is significant morbidity and mortality associated with severe pancreatic injury. Immediate resuscitation and investigations are essential to delineate the nature of the injury, and to plan further management. If main pancreatic duct injuries are identified, specialised input from a tertiary hepatopancreaticobiliary (HPB) team is advised. A comprehensive online literature search was performed using PubMed. Relevant articles from international journals were selected. The search terms used were: 'pancreatic trauma', 'pancreatic duct injury', 'radiology AND pancreas injury', 'diagnosis of pancreatic trauma', and 'management AND surgery'. Articles that were not published in English were excluded. All articles used were selected on relevance to this review and read by both authors. Pancreatic trauma is rare and associated with injury to other upper abdominal viscera. Patients present with non-specific abdominal findings and serum amylase is of little use in diagnosis. Computed tomography is effective in diagnosing pancreatic injury but not duct disruption, which is most easily seen on endoscopic retrograde cholangiopancreaticography or operative pancreatography. If pancreatic injury is suspected, inspection of the entire pancreas and duodenum is required to ensure full evaluation at laparotomy. The operative management of pancreatic injury depends on the grade of injury found at laparotomy. The most important prognostic factor is main duct disruption and, if found, reconstructive options should be determined by an experienced HPB surgeon. The diagnosis of pancreatic trauma requires a high index of suspicion and detailed imaging studies. Grading pancreatic injury is important to guide operative management. The most important prognostic factor is pancreatic duct disruption and in these cases

  20. Liver, pancreas and biliary tract enhanced lipoperoxidation products in pure pancreatic juice: evidence for organ-specific oxidative stress in chronic pancreatitis.

    PubMed

    Santini, S A; Spada, C; Bononi, F; Foschia, F; Mutignani, M; Perri, V; Giardina, B; Silveri, N Gentiloni; Costamagna, G

    2003-12-01

    Oxygen-free radicalscan play a role in the development of chronic pancreatitis, altering the redox state with damage of cell constituents and decrease in antioxidant defences. To measure levels of lipoperoxidation products, conjugated dienes and lipid hydroperoxides, in pure pancreatic juice and serum of chronic pancreatitis patients and compare them to that in controls. To investigate a possible correlation with serum indexes of pancreatic inflammation (amylase and lipase). Pancreatic juice was collected during ERCP, after secretin stimulation, in 20 patients with chronic pancreatitis and 11 controls with biliary diseases. Lipid hydroperoxide levels were determined with FOX2 method and measured as absorbance at 560 nm. Conjugated diene levels were measured using second-derivative spectroscopy. No substantial difference was present in serum levels of lipid hydroperoxides, conjugated dienes (in both isomeric forms) and isomer-ratio values between those of patients with chronic pancreatitis and controls. In pancreatic juice, there was a significant increase in lipid hydroperoxides and conjugated dienes levels (especially trans-trans isomers) in chronic pancreatitis patients compared with controls, with a decrease in cis-trans isomers and a significant difference in isomer-ratio values. Increased levels of lipid hydroperoxides and conjugated dienes in the pancreatic juice of chronic pancreatitis patients is indicative of an enhanced lipoperoxidation and antioxidants consumption in pancreatic tissue, confirmed by the decreased isomer-ratio values as an indirect index of decreased antioxidant capacity. The lack of significant difference in conjugated diene and lipid hydroperoxide levels in the serum of chronic pancreatitis patients versus that of controls suggests an oxidative stress limited to pancreatic tissue and indicative of an organ-specific pathology, confirmed by the parallel behaviour of oxidative parameters (lipid hydroperoxides and conjugated dienes) and

  1. Diagnosing Chronic Pancreatitis.

    PubMed

    Anaizi, Ahmad; Hart, Phil A; Conwell, Darwin L

    2017-07-01

    Diagnosing CP can range from routine in those with severe disease and obvious calcifications on CT imaging to elusive in those patients with early changes in CP. The workup of suspected CP should follow a progressively noninvasive to more invasive STEP-wise approach in a patient with a suspicious clinical presentation and risk factors that raise their pretest probability of disease. After a thorough history and physical examination, basic laboratories should be obtained such as lipase, amylase, metabolic panel, and indirect PFTs (fecal elastase-1, serum trypsin). Computed tomography remains the best initial imaging modality to obtain as it has good sensitivity for severe CP and may obviate the need for other diagnostic tests. When equivocal, an MRCP should be obtained for a more detailed evaluation of the both the pancreatic parenchyma and ducts. If the diagnosis remains in doubt, EUS should be performed with or without pancreas function testing. ERCP remains a last-line diagnostic test and seldom should be used outside of therapeutic purposes. Future advances should target optimizing current diagnostic tools to more accurately diagnose early CP, as it is in this population where the benefits of delaying progression of CP may have the most profound effect. Likely the best way at establishing a diagnosis in these patients is via pancreatic function testing in the setting of indeterminate EUS results. Biomarker studies of pancreas fluid may supplement diagnosis.

  2. Hydrolysis of bovine and caprine milk fat globules by lipoprotein lipase. Effects of heparin and skim milk on lipase distribution and on lipolysis

    SciTech Connect

    Sundheim, G.; Bengtsson-Olivecrona, G.

    1987-12-01

    Heparin can dissociate lipoprotein lipase from casein micelles, and addition of heparin enhances lipolysis in bovine but not in caprine milk. Heparin shortened the lag-time for binding of lipoprotein lipase to milk fat globules and for lipolysis. Heparin counteracted the inhibitory effects of skim milk on binding of lipase and on lipolysis. Heparin stimulated lipolysis in all bovine milk samples when added before cooling and in spontaneously lipolytic milk samples also when added after cooling. Heparin enhanced lipolysis of isolated milk fat globules. Hence, its effect is not solely due to dissociation of lipoprotein lipase from the casein micelles. Coolingmore » of goat milk caused more marked changes in the distribution of lipase than cooling of bovine milk; the fraction of added /sup 125/I-labeled lipase that bound to cream increased from about 8 to 60%. In addition, caprine skim milk caused less inhibition of lipolysis than bovine skim milk. These observations provide an explanation for the high degree of cold storage lipolysis in goat milk. Heparin had only small effects on the distribution of lipoprotein lipase in caprine milk, which explains why heparin has so little effect on lipolysis in caprine milk. The distribution of /sup 35/S-labeled heparin in bovine milk was studied. In warm milk less than 10% bound to the cream fraction, but when milk was cooled, binding of heparin to cream increased to 45%. These results suggest that there exists in the skim fraction a relatively small amount of a heparin-binding protein, which on cooling of milk adsorbs to the milk fat, or suggests that cooling induces a conformational change in a membrane protein such that its affinity for heparin increases.« less

  3. Chronic pancreatitis.

    PubMed

    Yang, Dennis; Forsmark, Chris E

    2017-09-01

    Summarize key clinical advances in chronic pancreatitis reported in 2016. Early diagnosis of chronic pancreatitis remains elusive. Recent studies suggest that endoscopic ultrasound may be less accurate than previously thought and new MRI techniques may be helpful. Genetic predisposition may independently affect the clinical course of chronic pancreatitis and the risk for pancreatic cancer. Cigarette smoking may have a greater negative impact on chronic pancreatitis than previously thought and moderate alcohol consumption may be protective. A multidisciplinary approach is necessary for the treatment of type 3 diabetes and nutritional deficiencies in chronic pancreatitis. Although endoscopic therapy remains a reasonable first-line option in treating chronic pancreatitis and its complications, early surgical intervention may be indicated for pain in select patients. Newer endoscopic ultrasound and MRI techniques are being evaluated to help with the early diagnosis of chronic pancreatitis. Both genetic predisposition and cigarette smoking are increasingly recognized as having a major impact in the course of the disease and the risk for pancreatic cancer. Endoscopic therapy is well tolerated and effective for the treatment of chronic pancreatitis and its complications although an early surgical approach for pain may be associated with improved clinical outcomes.

  4. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    ClinicalTrials.gov

    2018-02-21

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

  5. Anti- and pro-lipase activity of selected medicinal, herbal and aquatic plants, and structure elucidation of an anti-lipase compound.

    PubMed

    Ado, Muhammad Abubakar; Abas, Faridah; Mohammed, Abdulkarim Sabo; Ghazali, Hasanah M

    2013-11-26

    Plants that help in slowing down the digestion of triacylglycerols (TAGs) in the pancreas and small intestine of humans play an important role in the reduction of obesity. On the other hand, there may be plants or plant parts that stimulate intestinal lipolytic activity, thus contributing to greater TAG assimilation. The aim of this study was to evaluate the aqueous methanolic extracts of ninety eight (98) medicinal, herbal and aquatic plant materials from Malaysia for their effect on porcine pancreatic lipase (PPL) activity and to identify the structure of an anti-lipase compound from one of the sources. The degree of inhibition was also quantified as relative to orlistat activity against PPL (orlistat equivalents). Results revealed that while 19.4% of the extracts were found to have anti-lipase activity ≥80%, 12% were actually found to promote PPL activity. Twenty two percent (22.4%) exhibited moderate inhibition (41%-80%) and 2% were neutral toward PPL activity. The ripe fruit of Averrhoa carambola and the leaves of Archidendron jiringa (Jack) I.C Nielsen L. (jering), Cynometra cauliflora (nam-nam) and Aleurites moluccana (L.) Willd (candle nut/buah keras) had the highest (100%) anti-lipase activity and are equivalent to 0.11 µg orlistat/mL. Plants that stimulated lipase activity included Pimpinella anisum L. (aniseed/jintan manis), activating the enzyme by 186.5%. Kaempferol 3-O-rhamnoside was isolated from the ethyl acetate fraction of C. cauliflora leaves and found to be an active lipase inhibitor. The structure was elucidated using 1H-NMR, 13C-NMR and 2D-NMR analyses.

  6. Chronic pancreatitis.

    PubMed

    Majumder, Shounak; Chari, Suresh T

    2016-05-07

    Chronic pancreatitis describes a wide spectrum of fibro-inflammatory disorders of the exocrine pancreas that includes calcifying, obstructive, and steroid-responsive forms. Use of the term chronic pancreatitis without qualification generally refers to calcifying chronic pancreatitis. Epidemiology is poorly defined, but incidence worldwide seems to be on the rise. Smoking, drinking alcohol, and genetic predisposition are the major risk factors for chronic calcifying pancreatitis. In this Seminar, we discuss the clinical features, diagnosis, and management of chronic calcifying pancreatitis, focusing on pain management, the role of endoscopic and surgical intervention, and the use of pancreatic enzyme-replacement therapy. Management of patients is often challenging and necessitates a multidisciplinary approach. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Inhibition of secretin stimulated pancreatic secretion by pancreatic polypeptide.

    PubMed

    Adrian, T E; Besterman, H S; Mallinson, C N; Greenberg, G R; Bloom, S R

    1979-01-01

    The effect of PP on secretin-stimulated pancreatic secretion was assessed in five healthy subjects. During an intravenous infusion of BPP at a dose which produced plasma levels similar to those seen after meals in healthy young adults the volume and bicarbonate content of duodenal juice was reduced by 25% (p less than 0.05) and 24% (p less than 0.05) respectively, while protein and bilirubin concentrations were more markedly reduced by 68% (p less than 0.0005) and 67% (p less than 0.0005) respectively. PP, thus, may be an important inhibitory factor in the control of bilirubin and pancreatic enzyme secretion in man.

  8. Inhibition of secretin stimulated pancreatic secretion by pancreatic polypeptide.

    PubMed Central

    Adrian, T E; Besterman, H S; Mallinson, C N; Greenberg, G R; Bloom, S R

    1979-01-01

    The effect of PP on secretin-stimulated pancreatic secretion was assessed in five healthy subjects. During an intravenous infusion of BPP at a dose which produced plasma levels similar to those seen after meals in healthy young adults the volume and bicarbonate content of duodenal juice was reduced by 25% (p less than 0.05) and 24% (p less than 0.05) respectively, while protein and bilirubin concentrations were more markedly reduced by 68% (p less than 0.0005) and 67% (p less than 0.0005) respectively. PP, thus, may be an important inhibitory factor in the control of bilirubin and pancreatic enzyme secretion in man. PMID:761835

  9. Influence of atropine therapy on fenthion-induced pancreatitis.

    PubMed

    Ela, Yuksel; Fidan, Huseyin; Sahin, Onder; Kilbas, Aynur; Bas, Orhan; Yavuz, Yucel; Kucuker, Hudaverdi; Altuntas, Irfan

    2008-02-01

    We searched the influence of dose and timing of atropine therapy in fenthion-induced pancreatitis model. All rats were intoxicated with fenthion except the control group. Two milligrams of atropine was administered for 24 hours in a high dose atropine group while a low dose atropine group received 100 micrograms of atropine for 24 hours. One group received 2 milligrams of atropine in the first four hours of intoxication while the other group received 2 milligrams of atropine in the last four hours before sacrifice. All rats were sacrificed 24 hours after intoxication. Pseudo-cholinesterase and lipase concentrations and histopathological markers of pancreatitis were studied. None of the models in this study completely prevented pancreatitis, however high dose atropine that is administered for 24 hours or the first four hours after intoxication prevented severe pancreatitis. Atropine administration influence on fenthion-induced pancreatitis should be studied for other organophosphates in animals and humans.

  10. An ultraviolet spectrophotometric assay for the screening of sn-2-specific lipases using 1,3-O-dioleoyl-2-O-α-eleostearoyl-sn-glycerol as substrate

    PubMed Central

    Mendoza, Lilia D.; Rodriguez, Jorge A.; Leclaire, Julien; Buono, Gerard; Fotiadu, Frédéric; Carrière, Frédéric; Abousalham, Abdelkarim

    2012-01-01

    In the present study, we propose a continuous assay for the screening of sn-2 lipases by using triacylglycerols (TAGs) from Aleurites fordii seed (tung oil) and a synthetic TAG containing the α-eleostearic acid at the sn-2 position and the oleic acid (OA) at the sn-1 and sn-3 positions [1,3-O-dioleoyl-2-O-α-eleostearoyl-sn-glycerol (sn-OEO)]. Each TAG was coated into a microplate well, and the lipase activity was measured by optical density increase at 272 nm due to transition of α-eleostearic acid from the adsorbed to the soluble state. The sn-1,3-regioselective lipases human pancreatic lipase (HPL), LIP2 lipase from Yarrowia lipolytica (YLLIP2), and a known sn-2 lipase, Candida antarctica lipase A (CALA) were used to validate this method. TLC analysis of lipolysis products showed that the lipases tested were able to hydrolyze the sn-OEO and the tung oil TAGs, but only CALA hydrolyzed the sn-2 position. The ratio of initial velocities on sn-OEO and tung oil TAGs was used to estimate the sn-2 preference of lipases. CALA was the enzyme with the highest ratio (0.22 ± 0.015), whereas HPL and YLLIP2 showed much lower ratios (0.072 ± 0.026 and 0.038 ± 0.016, respectively). This continuous sn-2 lipase assay is compatible with a high sample throughput and thus can be applied to the screening of sn-2 lipases. PMID:22114038

  11. Chronic pancreatitis.

    PubMed

    Gupte, Anand R; Forsmark, Chris E

    2014-09-01

    We review selected important clinical observations in chronic pancreatitis reported in 2013. Early diagnosis of chronic pancreatitis remains difficult, although newer techniques utilizing endoscopic ultrasonography-elastography and MRI hold promise. Patients with chronic pancreatitis are at risk of nutritional deficiencies. Osteoporosis, osteopenia, and bone fracture are particularly common in these patients, and require active intervention and treatment. Diabetes caused by chronic pancreatitis, type 3c diabetes, has specific characteristics and requires careful management. Antioxidants and neuromodulators may decrease pain in some patients with chronic pancreatitis. Endoscopic treatment is effective and can be utilized in patients with painful chronic pancreatitis, although randomized trials demonstrate that surgical therapy is somewhat more durable and effective. Although surgery has typically been a last resort, some advocate early surgical intervention but the optimal time remains unknown. Early diagnosis of pancreatitis may be improved by newer techniques associated with endoscopic ultrasonography imaging. Treatment of nutritional deficiencies and diabetes is an important aspect of treating chronic pancreatitis. Pain relief with adjunct means of pain modulation should be tried before starting narcotics for pain control. Endoscopic therapy is appropriate for treating chronic pancreatitis and its local complications and surgical intervention can be considered early in carefully selected individuals.

  12. Acute pancreatitis.

    PubMed

    Talukdar, Rupjyoti; Vege, Santhi S

    2015-09-01

    To summarize recent data on classification systems, cause, risk factors, severity prediction, nutrition, and drug treatment of acute pancreatitis. Comparison of the Revised Atlanta Classification and Determinant Based Classification has shown heterogeneous results. Simvastatin has a protective effect against acute pancreatitis. Young black male, alcohol, smoldering symptoms, and subsequent diagnosis of chronic pancreatitis are risk factors associated with readmissions after acute pancreatitis. A reliable clinical or laboratory marker or a scoring system to predict severity is lacking. The PYTHON trial has shown that oral feeding with on demand nasoenteric tube feeding after 72 h is as good as nasoenteric tube feeding within 24 h in preventing infections in predicted severe acute pancreatitis. Male sex, multiple organ failure, extent of pancreatic necrosis, and heterogeneous collection are factors associated with failure of percutaneous drainage of pancreatic collections. The newly proposed classification systems of acute pancreatitis need to be evaluated more critically. New biomarkers are needed for severity prediction. Further well designed studies are required to assess the type of enteral nutritional formulations for acute pancreatitis. The optimal minimally invasive method or combination to debride the necrotic collections is evolving. There is a great need for a drug to treat the disease early on to prevent morbidity and mortality.

  13. TRAUMATIC PANCREATITIS

    PubMed Central

    Berne, Clarence J.; Walters, Robert L.

    1953-01-01

    Traumatic pancreatitis should be considered as a diagnostic possibility when trauma to the epigastrium is followed by phenomena suggestive of intra-abdominal injury. The presence or absence of hyperamylasemia should be established immediately. Even when traumatic pancreatitis is believed to exist, any suggestion of injury to other viscera should indicate laparotomy. Retroperitoneal rupture of the duodenum may simulate traumatic pancreatitis in all respects, including hyperamylasemia. X-ray studies may be of value in differentiation. Non-complicated traumatic pancreatitis is best treated conservatively. Gunshot and knife wounds of the pancreas should be drained. PMID:13094537

  14. [Massive pleural effusion complicating chronic pancreatitis. Treatment by endoscopic closure of a pancreatic-mediastinal fistula].

    PubMed

    Trudzinski, F C; Rädle, J; Treiber, G; Kramm, T; Sybrecht, G W

    2008-11-01

    A 53-year-old man was admitted because of anuria, dyspnea and a septic temperature. The patients' history included chronic alcoholism, chronic pancreatitis, COPD and a right nephrectomy because of nephrolithiasis. Urosepsis was initially suspected. The patients' clinical condition and nutritional state were severely reduced. Laboratory findings revealed severe systemic inflammation (leucocyte count: 22.4/nl, CRP: 324 mg/l). Computed tomography showed a large left-sided pleural effusion, encapsulated abdominal fluid below the diaphragm and alongside the pancreatic tail. After aspiration of the pleural effusion the diagnosis of an exsudate with elevated concentration of lipase (56,000 U/l) was confirmed. Endoscopic ultrasound showed a 3-4 cm pseudocystic mass originating in the region of the pancreatic tail. The ERP depicted chronic pancreatitis with strictures and destruction of the pancreatic duct. Two fistulae were identified, one proximal to a ductal stricture in the pancreatic head and a second one in the pancreatic tail which corresponded to the reported pseudocyst. The patient was admitted to the ICU with symptoms of impending sepsis. The pleural effusion was treated with CT-guided chest drainage. The initial endoscopic attempt at stent closure of the fistula failed because it was possible to pass through the ductal stricture only with a thin hydrophilic wire and small-lumen catheter. However, injection of fibrin glue into the proximal pancreatic duct over a length of 2 cm obliterated the fistula and the pleural effusion was resolved. Pancreatic-pleural or pancreatic-mediastinal fistula is a rare complication of pancreatitis associated with unilateral pleural effusion. Combined internal endoscopic drainage and external chest drainage is the treatment of choice. After failure of routine endoscopic therapy, endoscopic closure of fistulas using fibrin glue might offer an alternative treatment strategy.

  15. Heparin and insulin in the management of hypertriglyceridemia-associated pancreatitis: case series and literature review.

    PubMed

    Kuchay, Mohammad Shafi; Farooqui, Khalid J; Bano, Tarannum; Khandelwal, Manoj; Gill, Harmandeep; Mithal, Ambrish

    2017-01-01

    Severe hypertriglyceridemia accounts for up to 7% of all cases of acute pancreatitis. Heparin and insulin activate lipoprotein lipase (LPL), thereby reducing plasma triglyceride levels. However, the safety and efficacy of heparin and insulin in the treatment of hypertriglyceridemia-associated acute pancreatitis have not been well established yet. We successfully used heparin and insulin as first-line therapy in four consecutive patients with acute pancreatitis secondary to hypertriglyceridemia. In a literature search, we revised almost all reports published to date of patients managed successfully with this combination. Heparin and insulin appear to be a safe, effective, and inexpensive first-line therapy for hypertriglyceridemia-associated acute pancreatitis.

  16. Hemorheological abnormalities in lipoprotein lipase deficient mice with severe hypertriglyceridemia

    SciTech Connect

    Zhao Tieqiang; Guo Jun; Li Hui

    2006-03-24

    Severe hypertriglyceridemia (HTG) is a metabolic disturbance often seen in clinical practice. It is known to induce life-threatening acute pancreatitis, but its role in atherogenesis remains elusive. Hemorheological abnormality was thought to play an important role in pathogenesis of both pancreatitis and atherosclerosis. However, hemorheology in severe HTG was not well investigated. Recently, we established a severe HTG mouse model deficient in lipoprotein lipase (LPL) in which severe HTG was observed to cause a significant increase in plasma viscosity. Disturbances of erythrocytes were also documented, including decreased deformability, electrophoresis rate, and membrane fluidity, and increased osmotic fragility. Scanning electron microscopymore » demonstrated that most erythrocytes of LPL deficient mice deformed with protrusions, irregular appearances or indistinct concaves. Analysis of erythrocyte membrane lipids showed decreased cholesterol (Ch) and phospholipid (PL) contents but unaltered Ch/PL ratio. The changes of membrane lipids may be partially responsible for the hemorheological and morphologic abnormalities of erythrocytes. This study indicated that severe HTG could lead to significant impairment of hemorheology and this model may be useful in delineating the role of severe HTG in the pathogenesis of hyperlipidemic pancreatitis and atherosclerosis.« less

  17. Pancreatitis in Children.

    PubMed

    Sathiyasekaran, Malathi; Biradar, Vishnu; Ramaswamy, Ganesh; Srinivas, S; Ashish, B; Sumathi, B; Nirmala, D; Geetha, M

    2016-11-01

    Pancreatic disease in children has a wide clinical spectrum and may present as Acute pancreatitis (AP), Acute recurrent pancreatitis (ARP), Chronic pancreatitis (CP) and Pancreatic disease without pancreatitis. This article highlights the etiopathogenesis and management of pancreatitis in children along with clinical data from five tertiary care hospitals in south India [Chennai (3), Cochin and Pune].

  18. Pancreatic cancer

    PubMed Central

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

    2011-01-01

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

  19. Pancreatic surgery.

    PubMed

    Donahue, Timothy R; Reber, Howard A

    2013-09-01

    To summarize published research on pancreatic surgery over the past year. A number of studies aiming to reduce the costs associated with pancreatic surgery were reported. Retrospective analyses confirmed previous findings that neither the routine use of pancreatic duct stents decreases the rate of fistula formation nor does placement of a drain at the time of surgery change the morbidity in patients who develop one. Minimally invasive approaches, both laparoscopic and robot-assisted, are being performed more frequently to remove pancreatic cancers. A randomized trial confirmed that reinforcement of stapled closure during distal pancreatectomy reduces the rate of fistula formation. Controversy remains over whether small pancreatic neuroendocrine tumors need to be surgically resected or can be treated nonoperatively. Patients with chronic pancreatitis should be screened thoroughly before being offered surgical treatment; two studies reported preoperative factors that can be used to identify those most likely to experience pain relief. Studies published on pancreatic surgery last year focused on a wide-range of topics. The morbidity and mortality of patients undergoing pancreatic surgery continues to improve, and we anticipate that incorporation of these new findings will lead to even better outcomes.

  20. Pancreatic injury.

    PubMed

    Ahmed, Nasim; Vernick, Jerome J

    2009-12-01

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

  1. Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis by possible reduction of NLRP3 activation and up-regulation of NET expression.

    PubMed

    Li, Yong; Pan, Yiyuan; Gao, Lin; Lu, Guotao; Zhang, Jingzhu; Xie, Xiaochun; Tong, Zhihui; Li, Baiqiang; Li, Gang; Li, Weiqin

    2018-01-22

    Previous studies have shown that acute inflammation is associated with increased sympathetic activity, which in turn increases the inflammatory response and leads to organ damage. The present study aimed to investigate whether dexmedetomidine administration during acute pancreatitis (AP) lessens pancreatic pathological and functional injury and the inflammatory response, and to explore the underlying mechanisms. Mild pancreatitis was induced in mice with caerulein, and severe pancreatitis was induced with caerulein plus lipopolysaccharide (LPS). After pancreatitis induction, dexmedetomidine at 10 or 20 μg/kg was injected via the tail vein. Pancreatic pathological and functional injury was assessed by histology and serum levels of amylase and lipase, respectively. The inflammatory response was evaluated by determining serum levels of inflammatory factors. The expression of myeloperoxidase (MPO) was examined by immunohistochemistry. The expression of norepinephrine transporter (NET), NLRP3, pro-IL-1β, and interleukin (IL)-1β in pancreatic tissue was detected by Western blot and real-time PCR. Dexmedetomidine at 20 μg/kg significantly attenuated pancreatic pathological injury, reduced serum levels of amylase, lipase, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, and decreased the expression of MPO in pancreatic tissue in both mouse models of pancreatitis. In addition, dexmedetomidine at 20 μg/kg significantly down-regulated the expression of NLRP3, pro-IL-1β, and IL-1β in pancreatic tissue, but up-regulated the expression of NET in both mouse models. Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis possibly by reducing NLRP3 activation and up-regulating NET expression. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Moderate acute pancreatitis with pleural effusion and impaired kidney functions

    NASA Astrophysics Data System (ADS)

    Lumbantoruan, O. H.; Dairi, L. B.

    2018-03-01

    Acute pancreatitis is a pancreatic inflammatory reaction that is clinically characterized by acute abdominal pain accompanied by elevated amylase and lipase enzymes. A 57-year-old female patient came to the emergency department with the main complaint of localized pain in the epigastric region within the last three days. Blood pressure 130/90mmHg, pulse 90x/i, RR 20x/i, temperature 37°C, sub-icteric on the eyes and tenderness in the epigastric region. Laboratory findings were leukocytosis, increased amylase, and lipase, elevated liver enzymes, hypoalbuminemia, elevated Kidney Functions, acidosis, and hypoglycemia. Abdominal CT-Scan revealed a partially lobulated edge with solid and necrotic components of the caput pancreas and widespread suspicion to the pancreatic corpus. The mass appeared to cause widening of the biliary and intrahepatic systems with minimal right pleural effusion. The liverwas slightly enlarged. The patient was with acute pancreatitis and treated with the installation of an open nasogastric tube, and resuscitated with ringer lactate fluid followed by IVFD D5%. Patients fasted for three days before giving a low fat, protein diet, antibiotic and proton pump inhibitors for seven days. After nine days, amylase and lipase levels decreased with significant clinical improvement. The next three days, the patient was discharged.

  3. Properties of a membrane-bound triglyceride lipase of rapeseed (Brassica napus L.) cotyledons.

    PubMed

    Rosnitschek, I; Theimer, R R

    1980-04-01

    The properties of the alkaline lipase activity (EC 3.1.1.3) that was recovered almost completely from a microsomal membrane fraction of 4-d-old rapeseed (Brassica napus L.) cotyledons were studied employing a titrimetric test procedure. The apparent KM was 6.5 mmol l(-1), with emulgated sunflower oil as the substrate. The products of triglyceride hydrolysis in vitro were glycerol, free fatty acids, and minor amounts of mono- and diglycerides. Maximum lipase activity depended on the preincubation of the lipolytic membrane fraction in 0.15 mol l(-1) NaCl and on the presence of at least 0.1 mol l(-1) NaCl in the test mixture. Desoxycholate and up to 0.1 mol l(-1) CaCl2 also activated the enzyme while EDTA and detergents such as trito x-100, digitonin, tween 85, and sodium dodecylsulfate were inhibitory. The rapeseed lipase displayed a conspicuous substrate selectivity among different plant triglycerides; the activity was inversely correlated with the oleic acid content of the oils. Water-soluble triacetin and the phospholipid lecithin were not hydrolyzed. Increasing amounts of free fatty acids reduced lipase activity; erucic acid, a major component of rapeseed oil, exhibited the strongest effect, suggesting a possible role in the regulation of lipase activity in vivo. The data demonstrate that the lipolytic membrane fraction houses a triglyceride lipase with properties similar to other plant and animal lipases. It can both qualitatively and quantitatively account for the fat degradation in rapeseed cotyledons. The evidence that provides further reason to acknowledge the membranous appendices of the spherosomes as the intracellular site of lipolysis is discussed.

  4. Cloning and characterization of newly isolated lipase from Enterobacter sp. Bn12.

    PubMed

    Farrokh, Parisa; Yakhchali, Bagher; Karkhane, Ali Asghar

    2014-01-01

    A mesophilic Enterobacter sp. Bn12 producing an alkaline thermostable lipase was isolated from soil in Tehran, Iran. The lipase gene (ELBn12) was identified from a genomic library. Sequence analysis of the DNA fragment revealed an open reading frame of 879 bp encoding a lipase with a molecular mass of 31.3 kDa. The deduced amino acid sequence showed 96% identity with a lipase of Enterobacter sp. Ag1 and the identity of their DNA sequences was 88.9%. ELBn12 belongs to the lipase subfamily I.1 and its catalytic triad consists of Ser82, Asp237 and His259. The lipase was expressed in Escherichia coli (BL21) pLysS and partially purified by anion exchange chromatography. The maximum activity of ELBn12 was obtained at temperature of 60 °C and pH 8.0 towards tricaprylin (C8) and its specific activity was around 2900 U/mg. ELBn12 was stable within a broad pH range from 6.0 to 11.0. The enzyme showed high stability in both polar and nonpolar organic solvents at 50% (v/v). The lipase activity was enhanced in the presence of 10 mM of Ca(2+), Mg(2+) and K(+), while heavy metals (Fe(3+) and Zn(2+)) had strong inhibitory effect. ELBn12 showed high activity in the presence of 1% (w/v) nonionic surfactants, however ionic surfactants inhibited the lipolytic activity. ELBn12 characteristics show that it has a potential to be used in various industrial processes.

  5. Cloning and characterization of newly isolated lipase from Enterobacter sp. Bn12

    PubMed Central

    Farrokh, Parisa; Yakhchali, Bagher; Karkhane, Ali Asghar

    2014-01-01

    A mesophilic Enterobacter sp. Bn12 producing an alkaline thermostable lipase was isolated from soil in Tehran, Iran. The lipase gene (ELBn12) was identified from a genomic library. Sequence analysis of the DNA fragment revealed an open reading frame of 879 bp encoding a lipase with a molecular mass of 31.3 kDa. The deduced amino acid sequence showed 96% identity with a lipase of Enterobacter sp. Ag1 and the identity of their DNA sequences was 88.9%. ELBn12 belongs to the lipase subfamily I.1 and its catalytic triad consists of Ser82, Asp237 and His259. The lipase was expressed in Escherichia coli (BL21) pLysS and partially purified by anion exchange chromatography. The maximum activity of ELBn12 was obtained at temperature of 60 °C and pH 8.0 towards tricaprylin (C8) and its specific activity was around 2900 U/mg. ELBn12 was stable within a broad pH range from 6.0 to 11.0. The enzyme showed high stability in both polar and nonpolar organic solvents at 50% (v/v). The lipase activity was enhanced in the presence of 10 mM of Ca2+, Mg2+ and K+, while heavy metals (Fe3+ and Zn2+) had strong inhibitory effect. ELBn12 showed high activity in the presence of 1% (w/v) nonionic surfactants, however ionic surfactants inhibited the lipolytic activity. ELBn12 characteristics show that it has a potential to be used in various industrial processes. PMID:25242958

  6. Production of an extracellular thermohalophilic lipase from a moderately halophilic bacterium, Salinivibrio sp. strain SA-2.

    PubMed

    Amoozegar, Mohammad Ali; Salehghamari, Ensieh; Khajeh, Khosro; Kabiri, Mahbube; Naddaf, Saied

    2008-06-01

    Fifty strains of moderately halophilic bacteria were isolated from various salty environments in Iran. A strain designated as SA-2 was shown to be the best producer of extracellular lipase and was selected for further studies. Biochemical and physiological characterization along with 16S rDNA sequence analysis placed SA-2 in the genus Salinivibrio. The optimum salt, pH, temperature and aeration for enzyme production were 0.1 M KCl, pH 8, 35 degrees C and 150 rpm, respectively. The enzyme production was synchronized bacterial growth and reached a maximum level during the early-stationary phase in the basal medium containing 1 M NaCl. Triacylglycerols enhanced lipase production, while carbohydrates had inhibitory effects on it. The maximum lipase activity was obtained at pH 7.5, 50 degrees C and CaCl(2) concentration of 0.01 M. The enzyme was stable at pH range of 7.5-8 and retained 90% of its activity at 80 degrees C for 30 min. Different concentrations of NaNO(3), Na(2)SO(4), KCl and NaCl had no affect on lipase stability for 3 h. These results suggest that the lipase secreted by Salinivibrio sp. strain SA-2 is industrially important from the perspective of its tolerance to a broad temperature range, its moderate thermoactivity and its high tolerance to a wide range of salt concentrations (0-3 M NaCl).

  7. Crocus cancellatus subsp. damascenus stigmas: chemical profile, and inhibition of α-amylase, α-glucosidase and lipase, key enzymes related to type 2 diabetes and obesity.

    PubMed

    Loizzo, Monica R; Marrelli, Mariangela; Pugliese, Alessandro; Conforti, Filomena; Nadjafi, Farsad; Menichini, Francesco; Tundis, Rosa

    2016-01-01

    Spices are appreciated for their medicinal properties besides their use as food adjuncts to enhance the sensory quality of food. In this study, Crocus cancellatus subsp. damascenus was investigated for its antioxidant activities employing different in vitro systems. Stigma extract demonstrated a radical scavenging activity against both 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals with IC50 values of 34.6 and 21.6 µg/mL and a good ferric reducing ability (53.9 µM Fe(II)/g). In order to clarify the potential functional properties of this spice, the carbohydrate-hydrolysing enzymes and pancreatic lipase inhibitory properties were investigated. Crocus cancellatus subsp. damascenus extract inhibited α-amylase and α-glucosidase with IC50 values of 57.1 and 68.6 µg/mL, respectively. The bioactivity was discussed in terms of phytochemicals content. The obtained results may be of interest from a functional point of view or as food additive and to promote the revalorization of this species.

  8. Lipase Test: MedlinePlus Lab Test Information

    MedlinePlus

    ... page: https://medlineplus.gov/labtests/lipasetest.html Lipase Test To use the sharing features on this page, please enable JavaScript. What is a lipase test? Lipase is a type of protein made by ...

  9. An interfacial and comparative in vitro study of gastrointestinal lipases and Yarrowia lipolytica LIP2 lipase, a candidate for enzyme replacement therapy.

    PubMed

    Bénarouche, Anaïs; Point, Vanessa; Carrière, Frédéric; Cavalier, Jean-François

    2014-07-01

    Lipolytic activities of Yarrowia lipolytica LIP2 lipase (YLLIP2), human pancreatic (HPL) and dog gastric (DGL) lipases were first compared using lecithin-stabilized triacylglycerol (TAG) emulsions (Intralipid) at various pH and bile salt concentrations. Like DGL, YLLIP2 was able to hydrolyze TAG droplets covered by a lecithin monolayer, while HPL was not directly active on that substrate. These results were in good agreement with the respective kinetics of adsorption on phosphatidylcholine (PC) monomolecular films of the same three lipases, YLLIP2 being the most tensioactive lipase. YLLIP2 adsorption onto a PC monolayer spread at the air/water interface was influenced by pH-dependent changes in the enzyme/lipid interfacial association constant (KAds) which was optimum at pH 6.0 on long-chain egg PC monolayer, and at pH 5.0 on medium chain dilauroylphosphatidylcholine film. Using substrate monolayers (1,2-dicaprin, trioctanoin), YLLIP2 displayed the highest lipolytic activities on both substrates in the 25-35 mN m(-1) surface pressure range. YLLIP2 was active in a large pH range and displayed a pH-dependent activity profile combining DGL and HPL features at pH values found in the stomach (pH 3-5) and in the intestine (pH 6-7), respectively. The apparent maximum activity of YLLIP2 was observed at acidic pH 4-6 and was therefore well correlated with an efficient interfacial binding at these pH levels, whatever the type of interfaces (Intralipid emulsions, substrate or PC monolayers). All these findings support the use of YLLIP2 in enzyme replacement therapy for the treatment of pancreatic exocrine insufficiency, a pathological situation in which an acidification of intestinal contents occurs. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  10. Chronic pancreatitis.

    PubMed

    Kleeff, Jorg; Whitcomb, David C; Shimosegawa, Tooru; Esposito, Irene; Lerch, Markus M; Gress, Thomas; Mayerle, Julia; Drewes, Asbjørn Mohr; Rebours, Vinciane; Akisik, Fatih; Muñoz, J Enrique Domínguez; Neoptolemos, John P

    2017-09-07

    Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood. Chronic pancreatitis is characterized by ongoing inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Functional consequences include recurrent or constant abdominal pain, diabetes mellitus (endocrine insufficiency) and maldigestion (exocrine insufficiency). Diagnosing early-stage chronic pancreatitis is challenging as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts; pseudocysts; intrapancreatic bile duct stricturing; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis. Treatment options comprise medical, radiological, endoscopic and surgical interventions, but evidence-based approaches are limited. This Primer highlights the major progress that has been made in understanding the pathophysiology, presentation, prevalence and management of chronic pancreatitis and its complications.

  11. Inhibition of dog and human gastric lipases by enantiomeric phosphonate inhibitors: a structure-activity study.

    PubMed

    Miled, Nabil; Roussel, Alain; Bussetta, Cécile; Berti-Dupuis, Liliane; Rivière, Mireille; Buono, Gérard; Verger, Robert; Cambillau, Christian; Canaan, Stéphane

    2003-10-14

    The crystal structures of gastric lipases in the apo form [Roussel, A., et al. (1999) J. Biol. Chem. 274, 16995-17002] or in complex with the (R(P))-undecyl butyl phosphonate [C(11)Y(4)(+)] [Roussel, A., et al. (2002) J. Biol. Chem. 277, 2266-2274] have improved our understanding of the structure-activity relationships of acid lipases. In this report, we have performed a kinetic study with dog and human gastric lipases (DGL and HGL, respectively) using several phosphonate inhibitors by varying the absolute configuration of the phosphorus atom and the chain length of the alkyl/alkoxy substituents. Using the two previously determined structures and that of a new crystal structure obtained with the other (S(P))-phosphonate enantiomer [C(11)Y(4)(-)], we constructed models of phosphonate inhibitors fitting into the active site crevices of DGL and HGL. All inhibitors with a chain length of fewer than 12 carbon atoms were found to be completely buried in the catalytic crevice, whereas longer alkyl/alkoxy chains were found to point out of the cavity. The main stereospecific determinant explaining the stronger inhibition of the S(P) enantiomers is the presence of a hydrogen bond involving the catalytic histidine as found in the DGL-C(11)Y(4)(-) complex. On the basis of these results, we have built a model of the first tetrahedral intermediate corresponding to the tristearoyl-lipase complex. The triglyceride molecule completely fills the active site crevice of DGL, in contrast with what is observed with other lipases such as pancreatic lipases which have a shallower and narrower active site. For substrate hydrolysis, the supply of water molecules to the active site might be achieved through a lateral channel identified in the protein core.

  12. Saw palmetto-induced pancreatitis.

    PubMed

    Jibrin, Ismaila; Erinle, Ayodele; Saidi, Abdulfattah; Aliyu, Zakari Y

    2006-06-01

    Saw palmetto is a frequently used botanical agent in benign prostatic enlargement (BPH). Although it has been reported to cause cholestatic hepatitis and many medical conditions, Saw palmetto has not been implicated in acute pancreatitis. We report a case of a probable Saw palmetto induced acute hepatitis and pancreatitis. A 55-year-old reformed alcoholic, sober for greater than 15 years, presented with severe non-radiating epigastric pain associated with nausea and vomiting. His only significant comorbidity is BPH for which he intermittently took Saw palmetto for about four years. Physical examination revealed normal vital signs, tender epigastrium without guarding or rebound tenderness. Cullen and Gray Turner signs were negative. Complete blood count and basic metabolic profile were normal. Additional laboratory values include a serum amylase: 2,152 mmol/L, lipase: 39,346 mmol/L, serum triglyceride: 38 mmol/L, AST: 1265, ALT: 1232 and alkaline phosphatase was 185. Abdominal ultrasound and magnetic resonance cholangiography revealed sludge without stones. A hepatic indole diacetic acid scan was negative. Patient responded clinically and biochemically to withdrawal of Saw palmetto. Two similar episodes of improvements followed by recurrence were noted with discontinuations and reinstitution of Saw Palmetto. Simultaneous and sustained response of hepatitis and pancreatitis to Saw palmetto abstinence with reoccurrence on reinstitution strongly favors drug effect. "Natural" medicinal preparations are therefore not necessarily safe and the importance of detailed medication history (including "supplements") cannot be over emphasized.

  13. The galactolipase activity of Fusarium solani (phospho)lipase.

    PubMed

    Jallouli, Raida; Othman, Houcemeddine; Amara, Sawsan; Parsiegla, Goetz; Carriere, Frédéric; Srairi-Abid, Najet; Gargouri, Youssef; Bezzine, Sofiane

    2015-03-01

    The purified (phospho)lipase of Fusarium solani (FSL), was known to be active on both triglycerides and phospholipids. This study aimed at assessing the potential of this enzyme in hydrolyzing galactolipids. FSL was found to hydrolyze at high rates of synthetic medium chains monogalactosyldiacylglycerol (4658±146U/mg on DiC8-MGDG) and digalactosyldiacylglycerol (3785±83U/mg on DiC8-DGDG) and natural long chain monogalactosyldiacylglycerol extracted from leek leaves (991±85U/mg). It is the microbial enzyme with the highest activity on galactolipids identified so far with a level of activity comparable to that of pancreatic lipase-related protein 2. FSL maximum activity on galactolipids was measured at pH8. The analysis of the hydrolysis product of natural MGDG from leek showed that FSL hydrolyzes preferentially the ester bond at the sn-1 position of galactolipids. To investigate the structure-activity relationships of FSL, a 3D model of this enzyme was built. In silico docking of medium chains MGDG and DGDG and phospholipid in the active site of FSL reveals structural solutions which are in concordance with in vitro tests. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Parathyroid hormone is not an inhibitor of lipoprotein lipase activity.

    PubMed

    Arnadottir, M; Nilsson-Ehle, P

    1994-01-01

    The reduced lipoprotein lipase (LPL) activities in uraemia are reflected by increased serum triglyceride concentrations and reduced HDL cholesterol concentrations. Both hyperparathyroidism and circulating inhibitor(s) of LPL have been associated with the disturbances of lipid metabolism in uraemia. The aim of the present study was to investigate if parathyroid hormone (PTH) had an inhibitory effect on LPL activity. Plasma post-heparin LPL activities, plasma LPL inhibitory activities, serum PTHintact and serum PTHC-terminal concentrations were analysed in 20 patients on haemodialysis and 20 healthy controls. The effects of purified, human PTHintact and a carboxyterminal fragment of PTH (PTH39-84) on LPL activities in post-heparin plasma from healthy individuals and on the enzyme activity of purified, bovine milk LPL, activated with apolipoprotein CII, were studied. Patients had significantly higher plasma LPL inhibitory activities than controls, but there was no correlation between plasma LPL inhibitory activities and serum PTH concentrations. Neither PTHintact nor PTH39-84 had a significant effect on LPL activities in vitro. Thus there was no evidence of a direct inhibition of LPL activity by PTH under the present in-vivo or in-vitro conditions.

  15. Inhibitory effect of leaves extracts of Ocimum basilicum and Ocimum gratissimum on two key enzymes involved in obesity and hypertension in vitro

    PubMed Central

    Irondi, Emmanuel Anyachukwu; Agboola, Samson Olalekan; Oboh, Ganiyu; Boligon, Aline Augusti

    2016-01-01

    Aim: To evaluate the phenolics composition and inhibitory effect of the leaves extracts of Ocimum basilicum and Ocimum gratissimum on two key enzymes (pancreatic lipase [PL] and angiotensin 1-converting enzyme [ACE]) involved in obesity and hypertension in vitro. Materials and Methods: The phenolics (flavonoids and phenolic acids) were quantified using high-performance liquid chromatography coupled with diode array detection. PL and ACE inhibitory effects; DPPH* and ABTS*+ scavenging activities of the extracts were tested using spectrophotometric methods. Results: O. basilicum had the following major phenolics: Rutin, quercetin, and quercitrin (flavonoids); caffeic, chlorogenic, and gallic acids (phenolic acids); while O. gratissimum had the following major phenolics: Rutin, quercitrin, and luteolin (flavonoids); ellagic and chlorogenic acids (phenolic acids). “Extracts of both plants inhibited PL and ACE; scavenged DPPH* in a dose-dependent manner”. O. gratissimum extract was more potent in inhibiting PL (IC50: 20.69 µg/mL) and ACE (IC50: 29.44 µg/mL) than O. basilicum (IC50: 52.14 µg/mL and IC50: 64.99 µg/mL, against PL and ACE, respectively). O. gratissimum also scavenged DPPH* and ABTS*+ more than O. basilicum. Conclusion: O. basilicum and O. gratissimum leaves could be used as functional foods for the management of obesity and obesity-related hypertension. However, O. gratissimum may be more effective than O. basilicum. PMID:27757270

  16. Maturation of hepatic lipase. Formation of functional enzyme in the endoplasmic reticulum is the rate-limiting step in its secretion.

    PubMed

    Ben-Zeev, Osnat; Doolittle, Mark H

    2004-02-13

    Among three lipases in the lipase gene family, hepatic lipase (HL), lipoprotein lipase, and pancreatic lipase, HL exhibits the lowest intracellular specific activity (i.e. minimal amounts of catalytic activity accompanied by massive amounts of inactive lipase mass in the endoplasmic reticulum (ER)). In addition, HL has a distinctive sedimentation profile, where the inactive mass overlaps the region containing active dimeric HL and trails into progressively larger molecular forms. Eventually, at least half of the HL inactive mass in the ER reaches an active, dimeric conformation (t(1/2) = 2 h) and is rapidly secreted. The remaining inactive mass is degraded. HL maturation occurs in the ER and is strongly dependent on binding to calnexin in the early co-/post-translational stages. Later stages of HL maturation occur without calnexin assistance, although inactive HL at all stages appears to be associated in distinct complexes with other ER proteins. Thus, unlike other lipases in the gene family, HL maturation is the rate-limiting step in its secretion as a functional enzyme.

  17. In vitro digestion of the self-emulsifying lipid excipient Labrasol(®) by gastrointestinal lipases and influence of its colloidal structure on lipolysis rate.

    PubMed

    Fernandez, Sylvie; Jannin, Vincent; Chevrier, Stéphanie; Chavant, Yann; Demarne, Frédéric; Carrière, Frédéric

    2013-12-01

    Labrasol(®) is a self-emulsifying excipient used to improve the oral bioavailability of poorly water-soluble drugs. It is a mixture of acylglycerols and PEG esters, these compounds being substrates for digestive lipases. The characterization of Labrasol(®) gastrointestinal lipolysis is essential for understanding its mode of action. Labrasol(®) lipolysis was investigated using either individual enzymes (gastric lipase, pancreatic lipase-related protein 2, pancreatic carboxyl ester hydrolase) or a combination of enzymes under in vitro conditions mimicking first the gastric phase of lipolysis and second the duodenal one. Specific methods for quantifying lipolysis products were established in order to determine which compounds in Labrasol(®) were preferentially hydrolyzed. Gastric lipase showed a preference for di- and triacylglycerols and the main acylglycerols remaining after gastric lipolysis were monoacylglycerols. PEG-8 diesters were also hydrolyzed to a large extent by gastric lipase. Most of the compounds initially present in Labrasol(®) were found to be totally hydrolyzed after the duodenal phase of lipolysis. The rate of Labrasol(®) hydrolysis by individual lipases was found to vary significantly with the dilution of the excipient in water and the resulting colloidal structures (translucent dispersion; opaque emulsion; transparent microemulsion), each lipase displaying a distinct pattern depending on the particle size. The lipases with distinct substrate specificities used in this study were found to be sensitive probes of phase transitions occurring upon Labrasol(®) dilution. In addition to their use for developing in vitro digestion models, these enzymes are interesting tools for the characterization of self-emulsifying lipid-based formulations.

  18. Pancreatic cancer

    MedlinePlus

    ... JH, Kastan MB, Tepper JE, eds. Abeloff's Clinical Oncology . 5th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap ... Cancer Network website. NCCN clinical practice guidelines in oncology: pancreatic adenocarcinoma. Version 1.2018. www.nccn.org/ ...

  19. Pancreatitis - children

    MedlinePlus

    ... Stanton BF, St Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics. 20th ed. Philadelphia, PA: Elsevier; ... Pancreatic disease. In: Marcdante KJ, Kliegman RM, eds. Nelson Essentials of Pediatrics. 7th ed. Philadelphia, PA: Elsevier ...

  20. [Pancreatic trauma].

    PubMed

    Arvieux, C; Guillon, F; Létoublon, Ch; Oughriss, M

    2003-10-01

    Early diagnosis of pancreatic trauma has always been challenging because of the lack of correlation between the initial clinical symptomatology, radiologic and laboratory findings, and the severity of the injury. Thanks to the improved performance of spiral CT scanning and magnetic resonance pancreatography, it is now often possible to make an early diagnosis of pancreatic contusion, to localize the site of the injury, and (most importantly) to identify injury to the main pancreatic duct which has major implications for the management of the case. When the trauma victim is unstable, radiologic work-up may be impossible and urgent laparotomy is required. Control of hemorrhage is the primary concern here and a damage control approach with packing may be appropriate; if the pancreatic head has been destroyed, a pancreaticoduodenectomy with delayed reconstruction may be required. If the trauma victim is stable, the treatment strategy will be governed by a variety of parameters--age, clinical condition, associated local anatomic findings (pancreatitis, injury to the duodenum or biliary tract), involvement of the pancreatic duct, and localization of the injury within the gland (to right or left of the mesenteric vessels).

  1. Severe hypertriglyceridemia-related acute pancreatitis.

    PubMed

    Stefanutti, Claudia; Labbadia, Giancarlo; Morozzi, Claudia

    2013-04-01

    Acute pancreatitis is a potentially life-threatening complication of severe hypertriglyceridemia. In some cases, inborn errors of metabolism such as lipoprotein lipase deficiency, apoprotein C-II deficiency, and familial hypertriglyceridemia have been reported as causes of severe hypertriglyceridemia. More often, severe hypertriglyceridemia describes various clinical conditions characterized by high plasma levels of triglycerides (>1000 mg/dL), chylomicron remnants, or intermediate density lipoprotein like particles, and/or chylomicrons. International guidelines on the management of acute pancreatitis are currently available. Standard therapeutic measures are based on the use of lipid-lowering agents (fenofibrate, gemfibrozil, niacin, Ω-3 fatty acids), low molecular weight heparin, and insulin in diabetic patients. However, when standard medical therapies have failed, non-pharmacological approaches based upon the removal of triglycerides with therapeutic plasma exchange can also provide benefit to patients with severe hypertriglyceridemia and acute pancreatitis. Plasma exchange could be very helpful in reducing triglycerides levels during the acute phase of hyperlipidemic pancreatitis, and in the prevention of recurrence. The current evidence on management of acute pancreatitis and severe hypertriglyceridemia, focusing on symptoms, treatment and potential complications is reviewed herein. © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

  2. Pancreatic injury in patients with septic shock: A literature review

    PubMed Central

    Chaari, Anis; Abdel Hakim, Karim; Bousselmi, Kamel; Etman, Mahmoud; El Bahr, Mohamed; El Saka, Ahmed; Hamza, Eman; Ismail, Mohamed; Khalil, Elsayed Mahmoud; Kauts, Vipin; Casey, William Francis

    2016-01-01

    Sepsis and septic shock are life threatening condition associated with high mortality rate in critically-ill patients. This high mortality is mainly related to the inadequacy between oxygen delivery and cellular demand leading to the onset of multiorgan dysfunction. Whether this multiorgan failure affect the pancreas is not fully investigated. In fact, pancreatic injury may occur because of ischemia, overwhelming inflammatory response, oxidative stress, cellular apoptosis and/or metabolic derangement. Increased serum amylase and/or lipase levels are common in patients with septic shock. However, imaging test rarely reveal significant pancreatic damage. Whether pancreatic dysfunction does affect the prognosis of patients with septic shock or not is still a matter of debate. In fact, only few studies with limited sample size assessed the clinical relevance of the pancreatic injury in this group of patients. In this review, we aimed to describe the epidemiology and the physiopathology of pancreatic injury in septic shock patients, to clarify whether it requires specific management and to assess its prognostic value. Our main finding is that pancreatic injury does not significantly affect the outcome in septic shock patients. Hence, increased serum pancreatic enzymes without clinical features of acute pancreatitis do not require further imaging investigations and specific therapeutic intervention. PMID:27559431

  3. Pancreatic Cancer Early Detection Program

    ClinicalTrials.gov

    2017-05-12

    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

  4. Antioxidant and anti-glycation capacities of some medicinal plants and their potential inhibitory against digestive enzymes related to type 2 diabetes mellitus.

    PubMed

    Franco, Rodrigo Rodrigues; da Silva Carvalho, Danúbia; de Moura, Francyelle Borges Rosa; Justino, Allisson Benatti; Silva, Heitor Cappato Guerra; Peixoto, Leonardo Gomes; Espindola, Foued Salmen

    2018-04-06

    Plants preparations are used by traditional medicine in the treatment of various diseases, such as type-2 diabetes mellitus. Some medicinal plants are capable of controlling the complications of this metabolic disease at different levels, for example, providing antioxidant compounds that act against oxidative stress and protein glycation and others which are capable of inhibiting the catalysis of digestive enzymes and thus contribute to the reduction of hyperglycemia and hyperlipidemia. Our objective was to investigate the antioxidant and anti-glycation activities of some medicinal plants and their potential inhibitory against α-amylase, α-glucosidase and pancreatic lipase activities. Based on the ethnobotanical researches carried out by academic studies conducted at the Federal University of Uberlandia, ten plants traditionally used in the treatment of type-2 diabetes mellitus were selected. Ethanol (EtOH) and hexane (Hex) extracts of specific parts of these plants were used in enzymatic assays to evaluate their inhibitory potential against α-amylase, α-glucosidase and lipase, as well as their antioxidant (DPPH, ORAC and FRAP) and anti-glycation (BSA/fructose model) capacities. The results indicate that EtOH extract of four of the ten analyzed plants exhibited more than 70% of antioxidant and anti-glycation capacities, and α-amylase and lipase inhibitory activities; no extract was able to inhibit more than 40% the α-glucosidase activity. The EtOH extracts of Bauhinia forficata and Syzygium. cumini inhibited α-amylase (IC 50 8.17 ± 2.24 and 401.8 ± 14.7 μg/mL, respectively), whereas EtOH extracts of B. forficata, Chamomilla recutita and Echinodorus grandiflorus inhibited lipase (IC 50 59.6 ± 10.8, 264.2 ± 87.2 and 115.8 ± 57.1 μg/mL, respectively). In addition, EtOH extracts of B. forficata, S. cumini, C. recutita and E. grandiflorus showed, respectively, higher antioxidant capacity (DPPH IC 50 0.7 ± 0.1, 2.5 ± 0.2, 1.3 ± 0.2 and 35.3 ± 9.0

  5. The smooth-hound lipolytic system: Biochemical characterization of a purified digestive lipase, lipid profile and in vitro oil digestibility.

    PubMed

    Achouri, Neila; Smichi, Nabil; Gargouri, Youssef; Miled, Nabil; Fendri, Ahmed

    2017-09-01

    In order to identify fish enzymes displaying novel biochemical properties, we choose the common smooth-hound (Mustelus mustelus) as a starting biological material to characterize the digestive lipid hydrolyzing enzyme. A smooth-hound digestive lipase (SmDL) was purified from a delipidated pancreatic powder. The SmDL molecular weight was around 50kDa. Specific activities of 2200 and 500U/mg were measured at pH 9 and 40°C using tributyrin and olive oil emulsion as substrates, respectively. Unlike known mammal pancreatic lipases, the SmDL was stable at 50°C and it retained 90% of its initial activity after 15min of incubation at 60°C. Interestingly, bile salts act as an activator of the SmDL. It's worth to notice that the SmDL was also salt-tolerant since it was active in the presence of high salt concentrations reaching 0.8M. Fatty acid (FA) analysis of oil from the smooth-hound viscera showed a dominance of unsaturated ones (UFAs). Interestingly, the major n-3 fatty acids were DHA and EPA with contents of 18.07% and 6.14%, respectively. In vitro digestibility model showed that the smooth hound oil was efficiently hydrolyzed by pancreatic lipases, which suggests the higher assimilation of fish oils by consumers. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Prevalence of increased canine pancreas-specific lipase concentrations in young dogs with parvovirus enteritis.

    PubMed

    Kalli, Irida V; Adamama-Moraitou, Katerina K; Patsika, Michael N; Pardali, Dimitra; Steiner, Jörg M; Suchodolski, Jan S; Menexes, George; Brellou, Georgia D; Rallis, Timoleon S

    2017-03-01

    Pancreatic abnormalities during canine parvovirus (CPV) enteritis have not been studied prospectively. The objective of this study was to evaluate the diagnostic significance of canine serum pancreas-specific lipase (Spec cPL) concentration in dogs with CPV enteritis for the presence of acute pancreatitis (AP). Puppies with naturally occurring CPV enteritis were recruited and prospectively allocated into 2 groups according to normal or increased serum Spec cPL concentration. Clinical signs, laboratory findings, and pancreas-associated variables were compared between groups, and the impact of possible AP on disease course, duration of hospitalization, and outcome was assessed. Serum Spec cPL concentration in 35 puppies was above the upper limit of the RI in 17/35 (48.6%) dogs (Group A) and within the RI in 18 dogs (Group B). An increased serum lipase activity was present in 29/35 (82.9%) dogs, and Group A dogs had a higher serum lipase activity than Group B (P = .006). Serum Spec cPL in Group A dogs was positively correlated with serum lipase activity at the day of presentation (r = .667; P = .003) and day of discharge (r = .628; P = .007). No statistically significant difference was found between groups (P = .233) for the presence of systemic inflammatory response syndrome (SIRS) (6/17 or 35.3% dogs Group A, and 8/18 or 44.4% dogs Group B), the disease course, duration of hospitalization, or outcome between groups. Increased serum Spec cPL is relatively common in dogs with CPV enteritis. However, such increases do not seem to correlate with the outcome of disease. © 2017 American Society for Veterinary Clinical Pathology.

  7. Risk Factors of Acute Pancreatitis in Oral Double Balloon Enteroscopy.

    PubMed

    Kopáčová, Marcela; Bureš, Jan; Rejchrt, Stanislav; Vávrová, Jaroslava; Bártová, Jolana; Soukup, Tomáš; Tomš, Jan; Tachecí, Ilja

    Double balloon enteroscopy (DBE) was introduced 15 years ago. The complications of diagnostic DBE are rare, acute pancreatitis is most redoubtable one (incidence about 0.3%). Hyperamylasemia after DBE seems to be a rather common condition respectively. The most probable cause seems to be a mechanical straining of the pancreas. We tried to identify patients in a higher risk of acute pancreatitis after DBE. We investigated several laboratory markers before and after DBE (serum cathepsin B, lactoferrin, E-selectin, SPINK 1, procalcitonin, S100 proteins, alfa-1-antitrypsin, hs-CRP, malondialdehyde, serum and urine amylase and serum lipase). Serum amylase and lipase rose significantly with the maximum 4 hours after DBE. Serum cathepsin and procalcitonin decreased significantly 4 hours after DBE compared to healthy controls and patients values before DBE. Either serum amylase or lipase 4 hours after DBE did not correlate with any markers before DBE. There was a trend for an association between the number of push-and-pull cycles and procalcitonin and urine amylase 4 hours after DBE; between procalcitonin and alfa-1-antitrypsin, cathepsin and hs-CRP; and between E-selectin and malondialdehyde 4 hours after DBE. We found no laboratory markers determinative in advance those patients in a higher risk of acute pancreatitis after DBE.

  8. [Application of a continual improvement approach to selecting diagnostic markers for acute pancreatitis in an emergency department].

    PubMed

    Salinas, María; Flores, Emilio; López-Garrigós, Maite; Díaz, Elena; Esteban, Patricia; Leiva-Salinas, Carlos

    2017-01-01

    To apply a continual improvement model to develop an algorithm for ordering laboratory tests to diagnose acute pancreatitis in a hospital emergency department. Quasi-experimental study using the continual improvement model (plan, do, check, adjust cycles) in 2 consecutive phases in emergency patients: amylase and lipase results were used to diagnose acute pancreatitis in the first phase; in the second, only lipase level was first determined; amylase testing was then ordered only if the lipase level fell within a certain range. We collected demographic data, number amylase and lipase tests ordered and the findings, final diagnosis, and the results of a questionnaire to evaluate satisfaction with emergency care. The first phase included 517 patients, of whom 20 had acute pancreatitis. For amylase testing sensitivity was 0.70; specificity, 0.85; positive predictive value (PPV), 17; and negative predictive value (NPV), 0.31. For lipase testing these values were sensitivity, 0.85; specificity, 0.96; PPV, 21, and NPV, 0.16. When both tests were done, sensitivity was 0.85; specificity 0.99; PPV, 85; and NPV, 0.15. The second phase included data for 4815 patients, 118 of whom had acute pancreatitis. The measures of diagnostic yield for the new algorithm were sensitivity, 0.92; specificity, 0.98; PPV, 46; and NPV, 0.08]. This study demonstrates a process for developing a protocol to guide laboratory testing in acute pancreatitis in the hospital emergency department. The proposed sequence of testing for pancreatic enzyme levels can be effective for diagnosing acute pancreatitis in patients with abdominal pain.

  9. Midkine is overexpressed in acute pancreatitis and promotes the pancreatic recovery in L-arginine-induced acute pancreatitis in mice.

    PubMed

    Cheng, Li; Qiao, Zhenguo; Xu, Chunfang; Shen, Jiaqing

    2017-06-01

    Midkine (MK) is involved in the pathogenesis of numerous malignancies, but the expression and effect of MK in acute pancreatitis (AP) have not been well studied and documented. In this study, the expression of MK was assayed in mice with L-arginine-induced AP. A recombinant human MK (rhMK) was introduced in this study to test the effect of MK on the L-arginine-induced AP. Serum amylase and lipase were assayed. Pancreas tissue samples were also collected for the evaluation of histological injury. Western blot and immunochemical staining of α-amylase and proliferating cell nuclear antigen were applied for the study of acinar regeneration in the pancreas. The elevation of MK expression was found in mice with AP induced by L-arginine. After rhMK administration, rhMK did not affect the severity of acute pancreatic injury in acute phase in L-arginine-induced pancreatitis in mice, in accordance with changes of serum amylase and lipase and the histological evaluation. But during the recovery phase, the area of remaining acinar cells was increased and the fibrosis was reduced in rhMK-treated mice. Furthermore, the expression of proliferating cell nuclear antigen and α-amylase was also upregulated after rhMK treatment. Midkine is over-expressed during AP in the animal model. Recombinant MK could promote the recovery of L-arginine-induced pancreatitis in mice. Therefore, MK may be involved in the regeneration of acinar cells in AP, and rhMK may be a possible therapeutic intervention for the repairment of AP. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  10. Administration of human recombinant activated protein C is not associated with pancreatic parenchymal haemorrhage in L-arginine-induced experimental acute pancreatitis.

    PubMed

    Jamdar, Saurabh; Babu, Benoy I; Nirmalan, Mahesh; Jeziorska, Maria; McMahon, Raymond F T; Siriwardena, Ajith K

    2013-11-10

    Microvascular thrombosis is a critical event in severe acute pancreatitis. Human recombinant activated protein C (Xigris®, Eli Lilly, Indianapolis, IN, USA) modulates the interplay between pro-inflammatory and pro-coagulant pathways and maintains microvascular patency. However, the anticoagulant properties of Xigris® may precipitate bleeding from the inflamed pancreas. This study tests the hypothesis that Xigris® can ameliorate experimental acute pancreatitis without causing pancreatic haemorrhage. Sprague Dawley rats were allocated as follows: Group 1: control (n=7); Group 2: acute pancreatitis (n=6); Group 3: administration of Xigris® 500 µg/kg body weight before induction of acute pancreatitis (n=6); and Group 4: Administration of Xigris® 500 µg/kg body weight 30 minutes after induction of acute pancreatitis (n=6). Acute pancreatitis was induced by intraperitoneal administration of L-arginine 300 mg/100 g body weight. Animals were sacrificed at 48 hours and biochemical, haematological, and histological markers of pancreatic haemorrhage and inflammation assessed. Median lipase in animals with acute pancreatitis was 10 U/mL (range: 7-16 U/mL) compared to 5.5 (range: 3-8 U/mL) in controls (P=0.028). Lipase was also elevated in animals given Xigris® both before (12 U/mL, range: 8-22 U/mL; P=0.031 vs. control group) and after (46 U/mL, range: 9-71 U/mL; P=0.015 vs. control group) induction of acute pancreatitis). Haemoglobin levels were similar among all groups (P=0.323). There was no histological evidence of pancreatic haemorrhage in animals treated with Xigris®. Pre-treatment with Xigris® was associated with a significant reduction in pancreatic injury. This effect was absent when Xigris® was administered after induction of acute pancreatitis. Xigris® did not lead to pancreatic haemorrhage in experimental acute pancreatitis. Administration of Xigris® prior to induction of acute pancreatitis was associated with amelioration of injury. This effect was

  11. [Pancreatic ultrasonography].

    PubMed

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

    2015-04-01

    Despite the recent technological advances in imaging, abdominal ultrasonography continues to be the first diagnostic test indicated in patients with a suspicion of pancreatic disease, due to its safety, accessibility and low cost. It is an essential technique in the study of inflammatory processes, since it not only assesses changes in pancreatic parenchyma, but also gives an indication of the origin (bile or alcoholic). It is also essential in the detection and tracing of possible complications as well as being used as a guide in diagnostic and therapeutic punctures. It is also the first technique used in the study of pancreatic tumors, detecting them with a sensitivity of around 70% and a specificity of 90%. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  12. Hydrogen Treatment Protects Mice Against Chronic Pancreatitis by Restoring Regulatory T Cells Loss.

    PubMed

    Chen, Luguang; Ma, Chao; Bian, Yun; Li, Jing; Wang, Tiegong; Su, Li; Lu, Jianping

    2017-01-01

    Chronic pancreatitis is an inflammatory disease of the pancreas characterized by progressive tissue destruction and fibrogenesis. The development of chronic pancreatitis is associated with immune cell dysregulation. Currently, the specific and effective treatment of chronic pancreatitis remains absent. By using an L-arginine induced chronic pancreatitis mouse model, we tested the therapeutic potential of hydrogen, a strong hydroxyl radicals scavenger, in the chronic pancreatitis model. Tissue inflammation, damage and fibrosis were analyzed on HE, TUNEL, MPO, and sirius staining. Pancreas levels of MDA content, SOD activity, TNF-α , IL-10 cytokine expression and serum amylase and lipase activity were determined by ELISA and absorbance assay. Apoptosis, T cells subtype proportion and intracellular level of reactive oxygen species (ROS) were analyzed by flow cytometry. Tregs adoptive transfer and CD25 neutralization were used to validate the role of Tregs in chronic pancreatitis. We found that hydrogen treatment significantly improved multiple symptoms of chronic pancreatitis. The number of Tregs was reduced in chronic pancreatitis mice, while hydrogen treatment restored the Treg loss by L-arginine administrations. Depletion of Tregs abolished the protective effect of hydrogen treatment in chronic pancreatitis. In vitro study showed that hydrogen blocked ROS generation in Tregs and promoted Tregs survival. Hydrogen treatment showed reliable benefits in controlling the severity of chronic pancreatitis. Our study supported that hydrogen could be used as a novel treatment in chronic pancreatitis patient in the future. © 2017 The Author(s). Published by S. Karger AG, Basel.

  13. Pancreatitis, panniculitis and polyarthritis (PPP-) syndrome caused by post-pancreatitis pseudocyst with mesenteric fistula. Diagnosis and successful surgical treatment. Case report and review of literature.

    PubMed

    Dieker, Wulf; Derer, Johannes; Henzler, Thomas; Schneider, Alexander; Rückert, Felix; Wilhelm, Torsten J; Krüger, Bernd

    2017-01-01

    Pancreatitis, panniculitis and polyarthritis syndrome is a very rare extra-pancreatic complication of pancreatic diseases. While in most cases this syndrome is caused by acute or chronic pancreatitis, we report a case of a 62-year-old man presenting with extensive intraosseous fat necrosis, polyarthritis and panniculitis caused by a post-pancreatitis pseudocyst with a fistula to the superior mesenteric vein and extremely high blood levels of lipase. This became symptomatic 2.5 years after an episode of acute pancreatitis and as in most cases abdominal symptoms were absent. Treatment by surgical resection of the pancreatic head with the pseudocyst and mesenteric fistula led to complete remission of all symptoms. A review of the literature revealed that all publications are limited to case reports. Most authors hypothesize that an unspecific damage can cause a secretion of pancreatic enzymes to the bloodstream leading to a systemic lipolysis and fat tissue necrosis, especially of subcutaneous tissue, bone marrow, inducing panniculitis, polyarthritis and osteonecrosis. Even if caused by an acute pancreatitis abdominal symptoms are often mild or absent in most cases leading to misdiagnosis and poor prognosis. While symptomatic treatment with NSAR and cortisone showed poor to moderate response, causal treatment can be successful depending on the underlying pancreatic disease. Copyright © 2017. Published by Elsevier Ltd.

  14. Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

    PubMed

    Warzecha, Zygmunt; Sendur, Paweł; Ceranowicz, Piotr; Cieszkowski, Jakub; Dembiński, Marcin; Sendur, Ryszard; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Olszanecki, Rafał; Kuśnierz-Cabala, Beata; Tomasz, Kaczmarzyk; Tomaszewska, Romana; Dembiński, Artur

    2017-04-21

    Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

  15. Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

    PubMed Central

    Warzecha, Zygmunt; Sendur, Paweł; Ceranowicz, Piotr; Cieszkowski, Jakub; Dembiński, Marcin; Sendur, Ryszard; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Olszanecki, Rafał; Kuśnierz-Cabala, Beata; Tomasz, Kaczmarzyk; Tomaszewska, Romana; Dembiński, Artur

    2017-01-01

    Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Results: Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Conclusion: Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats. PMID:28430136

  16. Evaluation of cellulose-binding domain fused to a lipase for the lipase immobilization.

    PubMed

    Hwang, Sangpill; Ahn, Jungoh; Lee, Sumin; Lee, Tai Gyu; Haam, Seungjoo; Lee, Kangtaek; Ahn, Ik-Sung; Jung, Joon-Ki

    2004-04-01

    A cellulose-binding domain (CBD) fragment of a cellulase gene of Trichoderma hazianum was fused to a lipase gene of Bacillus stearothermophilus L1 to make a gene cluster for CBD-BSL lipase. The specific activity of CBD-BSL lipase for oil hydrolysis increased by 33% after being immobilized on Avicel (microcrystalline cellulose), whereas those of CBD-BSL lipase and BSL lipase decreased by 16% and 54%, respectively, after being immobilized on silica gel. Although the loss of activity of an enzyme immobilized by adsorption has been reported previously, the loss of activity of the CBD-BSL lipase immobilized on Avicel was less than 3% after 12 h due to the irreversible binding of CBD to Avicel.

  17. [Implications of nutritional status for onset and characteristics of experimental acute pancreatitis in a mouse model].

    PubMed

    Arndt, S; Meyer, F; Brandt-Nedelev, B; Wartmann, T; Lippert, H; Halangk, W

    2013-08-01

    Due to uncontrolled activation of digestive enzymes produced within the pancreas, acute pancreatitis is a disease with a great potential for complications and variable course. Since the pathophysiological steps of human pancreatitis can only be inadequately investigated, various animal models were established to study the course of disease. The model of supramaximal caerulein stimulation allows to gain insights into intracellular events of the early phase of acute pancreatitis. Usually, overnight fasted animals are used for the model of acute pancreatitis to achieve a maximum zymogen granula accumulation and a standardised initial situation due to diminished secretion of CCK. Furthermore, the role of the nutritional state for pathogenesis and course of acute pancreatitis is controversially discussed. The aim of the study was to investigate the impact of the nutritional status on pancreatic injury in experimental acute pancreatitis. Using standardised supramaximal caerulein stimulation (dose: 50 µg/kg; time intervals, 1/h; max. 7×), acute oedematous interstitial pancreatitis in fasted and non-fasted mice was induced. Pancreatic injury was locally characterised by pancreatic oedema, histopathological alterations and the release of pancreatic enzyme to the serum while systemic alterations were objectified by IL-6, CRP und pulmonal MPO. 1) Increased pancreatic serum enzyme levels after induction of acute pancreatitis in non-fasted animals do not reflect a greater affection of the pancreas since amylase and lipase in serum and pancreatic tissue correlate proportionally. The induction of acute pancreatitis provoked release of 1.3 % and 0.7 % of amylase and lipase, respectively, independently of nutritional status. 2) Neither local nor systemic parameters of pancreatic injury were significantly altered by the nutritional regimen. Pathohistologic investigations revealed increase of zymogen granula portion and cell size in non-fasted mice but no further differences

  18. Lipase Maturation Factor 1 (Lmf1): Structure and Role in Lipase Folding and Assembly

    PubMed Central

    Ehrhardt, Nicole

    2014-01-01

    Purpose of review Lipase maturation factor 1 (LMF1) is a membrane-bound protein located in the endoplasmic reticulum (ER). It is essential to the folding and assembly (i.e., maturation) of a select group of lipases that include lipoprotein lipase (LPL), hepatic lipase (HL) and endothelial lipase (EL). The purpose of this review is to examine recent studies that have begun to elucidate the structure and function of LMF1, and to place it in the context of lipase folding and assembly. Recent findings Recent studies identified mutations in LMF1 that cause combined lipase deficiency and hypertriglyceridemia in humans. These mutations result in the truncation of a large, evolutionarily conserved domain called DUF1222, which is essential for interaction with lipases and their attainment of enzymatic activity. The structural complexity of LMF1 has been further characterized by solving its topology in the ER membrane. Recent studies indicate that in addition to LPL and HL, the maturation of EL is also dependent on LMF1. Based on its apparent specificity for dimeric lipases, LMF1 is proposed to play an essential role in the assembly and/or stabilization of head-to-tail lipase homodimers. Summary LMF1 functions in the maturation of a select group of secreted lipases that assemble into homodimers in the ER. These dimeric lipases include LPL, HL and EL, all of which contribute significantly to plasma triglyceride and HDL cholesterol levels in human populations. Future studies involving genetically engineered mouse models will be required to fully elucidate the role of LMF1 in normal physiology and disease. PMID:20224398

  19. Evidence-based clinical practice guidelines for chronic pancreatitis 2015.

    PubMed

    Ito, Tetsuhide; Ishiguro, Hiroshi; Ohara, Hirotaka; Kamisawa, Terumi; Sakagami, Junichi; Sata, Naohiro; Takeyama, Yoshifumi; Hirota, Morihisa; Miyakawa, Hiroyuki; Igarashi, Hisato; Lee, Lingaku; Fujiyama, Takashi; Hijioka, Masayuki; Ueda, Keijiro; Tachibana, Yuichi; Sogame, Yoshio; Yasuda, Hiroaki; Kato, Ryusuke; Kataoka, Keisho; Shiratori, Keiko; Sugiyama, Masanori; Okazaki, Kazuichi; Kawa, Shigeyuki; Tando, Yusuke; Kinoshita, Yoshikazu; Watanabe, Mamoru; Shimosegawa, Tooru

    2016-02-01

    Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition.

  20. Occurrence, clinical features and outcome of canine pancreatitis (80 cases).

    PubMed

    Pápa, Kinga; Máthé, Akos; Abonyi-Tóth, Zsolt; Sterczer, Agnes; Psáder, Roland; Hetyey, Csaba; Vajdovich, Péter; Vörös, Károly

    2011-03-01

    Medical records of 80 dogs diagnosed with acute pancreatitis during a 4-year period were evaluated regarding history, breed predilection, clinical signs and additional examination findings. Cases were selected if compatible clinical symptoms, increased serum activity of amylase or lipase and morphologic evidence of pancreatitis by ultrasonography, laparotomy or necropsy were all present. Like in other studies, neutered dogs had an increased risk of developing acute pancreatitis. Although breed predilection was consistent with earlier reports, some notable differences were also observed. Apart from Dachshunds, Poodles, Cocker Spaniels and Fox Terriers, the sled dogs (Laikas, Alaskan Malamutes) also demonstrated a higher risk for pancreatitis according to our results. Concurrent diseases occurred in 56 dogs (70%), diabetes mellitus (n = 29, 36%) being the most common. Clinical signs of acute pancreatitis were similar to those observed in other studies. The study group represented a dog population with severe acute pancreatitis, having a relatively high mortality rate (40%) compared to data of the literature. Breed, age, gender, neutering and body condition had no significant association with the outcome. Hypothermia (p = 0.0413) and metabolic acidosis (p = 0.0063) correlated significantly with poor prognosis and may serve as valuable markers for severity assessment in canine acute pancreatitis.

  1. Autoimmune Pancreatitis.

    PubMed

    Majumder, Shounak; Takahashi, Naoki; Chari, Suresh T

    2017-07-01

    Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disease of the pancreas that belongs to the spectrum of immunoglobulin G-subclass4-related diseases (IgG4-RD) and typically presents with obstructive jaundice. Idiopathic duct-centric pancreatitis (IDCP) is a closely related but distinct disease that mimics AIP radiologically but manifests clinically most commonly as recurrent acute pancreatitis in young individuals with concurrent inflammatory bowel disease. IgG4 levels are often elevated in AIP and normal in IDCP. Histologically, lymphoplasmacytic acinar inflammation and storiform fibrosis are seen in both. In addition, the histologic hallmark of IDCP is the granulocyte epithelial lesion: intraluminal and intraepithelial neutrophils in medium-sized and small ducts with or without granulocytic acinar inflammation often associated with destruction of ductal architecture. Initial treatment of both AIP and IDCP is with oral corticosteroids for duration of 4 weeks followed by a gradual taper. Relapses are common in AIP and relatively uncommon in IDCP, a relatively rare disease for which the natural history is not well understood. For patients with relapsing AIP, treatment with immunomodulators and more recently rituximab has been recommended. Although rare instances of pancreaticobiliary malignancy has been reported in patients with AIP, overall the lifetime risk of developing pancreatic cancer does not appear to be elevated.

  2. Abnormal serum pancreatic enzymes, but not pancreatitis, are associated with an increased risk of malignancy in patients with intraductal papillary mucinous neoplasms.

    PubMed

    Roch, Alexandra M; Parikh, Janak A; Al-Haddad, Mohammad A; DeWitt, John M; Ceppa, Eugene P; House, Michael G; Nakeeb, Attila; Schmidt, C Max

    2014-10-01

    Pancreatitis is associated with intraductal papillary mucinous neoplasm (IPMN). This association is in part due to inflammation from pancreatic ductal obstruction. Although the correlation between pancreatitis and the malignant potential of IPMN is unclear, the 2012 International Consensus Guidelines (ICG) consider pancreatitis a "worrisome feature." We hypothesized that serum pancreatic enzymes, markers of inflammation, are a better predictor of malignancy than pancreatitis in patients with IPMN. Between 1992 and 2012, 364 patients underwent resection for IPMN at a single university hospital. In the past decade, serum amylase and lipase were collected prospectively as an inflammatory marker in 203 patients with IPMN at initial surveillance and "cyst clinic" visits. The latest serum pancreatic enzyme values within 3 months preoperatively were studied. Pancreatitis was defined according to the 2012 revision of the Atlanta Consensus. Of the 203 eligible patients, there were 76 with pancreatitis. Pancreatitis was not associated with an increased rate of malignancy (P = .51) or invasiveness (P = .08). Serum pancreatic enzymes categorically outside of normal range (high or low) were also not associated with malignancy or invasiveness. In contrast, as a continuous variable, the higher the serum pancreatic enzymes were, the greater the rate of invasive IPMN. Of the 127 remaining patients without pancreatitis, serum pancreatic enzymes outside of normal range (low and high) were each associated with a greater rate of malignancy (P < .0001 and P = .0009, respectively). Serum pancreatic enzyme levels above normal range (high) were associated with a greater rate of invasiveness (P = .02). In patients with IPMN without a history of pancreatitis, serum pancreatic enzymes outside of the normal range are associated with a greater risk of malignancy. In patients with a history of pancreatitis, there is a positive correlation between the levels of serum pancreatic enzymes

  3. Acute pancreatitis associated with interferon and ribavirin therapy in patients with chronic hepatitis C.

    PubMed

    Chaudhari, Swati; Park, James; Anand, Bhupinderjit S; Pimstone, Neville R; Dieterich, Douglas T; Batash, Steven; Bini, Edmund J

    2004-06-01

    Acute pancreatitis is a rare complication of interferon (IFN) and ribavirin (RBV) therapy. The aim of this study was to determine the incidence, clinical presentation, and outcome of acute pancreatitis in patients with chronic hepatitis C virus (HCV) infection treated with IFN and RBV combination therapy. We conducted a retrospective review of 1706 HCV-infected patients treated with IFN alpha-2b and RBV. The diagnosis of drug-induced acute pancreatitis was made based on the presence of epigastric pain, elevated amylase and lipase levels, and the absence of other identifiable causes of pancreatitis. Acute pancreatitis was diagnosed in 7 of 1706 HCV-infected patients (0.4%; 95% CI, 0.2 to 0.8%) who were treated with IFN alpha-2b and RBV. The mean age of the patients (four males and three females) was 51.4 +/- 4.7 years and the median duration of therapy prior to development of pancreatitis was 12.0 weeks (range, 4.0-21.0 weeks). All patients presented with epigastric pain associated with nausea, vomiting, and/or fever. The median amylase and lipase values at the time of diagnosis of pancreatitis were 330.0 U/L (range, 182.0-1813.0 U/L) and 500.0 U/L (range, 171.0-2778.0 U/L), respectively. IFN and RBV were discontinued in all patients at the time of diagnosis and six of the seven patients were hospitalized; one patient refused hospital admission. Pancreatitis resolved in all seven patients and none of these individuals had recurrent pancreatitis during a median follow-up of 18.0 months (range, 3.0-27.0 months). In conclusion, IFN and RBV combination therapy is a potential cause of drug-induced pancreatitis in patients with chronic HCV. In these individuals, pancreatitis is often severe enough to warrant hospital admission, although symptoms resolve promptly after discontinuation of antiviral therapy.

  4. SPATHOLOBUS SUBERECTUS STEM EXTRACT IMPROVES THE PROTECTIVE EFFECT OF HEPARIN ON CERULEIN-INDUCED PANCREATITIS.

    PubMed

    Shao, Zhengyi

    2017-01-01

    The present study evaluates the effect of Spatholobus suberectus stem extract (SS) in the management of pancreatitis alone and in combination with heparin. Pancreatitis was induced pancreatitis by cerulean (50μg/kg, i.p.) five times at an interval of 1 h without any pretreatment of drug. Rats were treated with SS (100 and 200 mg/kg, p. o.) and heparin (150 U/kg, i.p.) alone and in combination for the duration of a week. Later pancreatic weight and blood flow was estimated and different biochemical parameters like concentration of D-dimer and Interleukin 1β (IL-Ιβ) and activity of amylase and lipase were determined in blood of pancreatitis rats. Moreover effect of drug treatment on DNA synthesis and histopathology was also estimated on cerulean induced pancreatitis rats. Results of this study suggest that treatment with SS alone and in combination with heparin significantly increase in prothrombin time and pancreatic blood flow than negative control group. There was significant decrease in concentration of IL-Ιβ and D-dimer and activity of amylase and lipase in SS and heparin treated group than negative control group. Pancreatic DNA synthesis was also found to be reduced in SS and heparin alone and in combination treated group. Histopathology study also reveals that treatment with SS and heparin alone and in combination reduces edema, hemorrhages, leukocyte infiltration in the TS of pancreatic tissues. Present study concludes that treatment with SS alone effectively manages the pancreatitis by ceasing the inflammatory pathway and potentiates the effect of heparin in the management of pancreatitis.

  5. No Benefit of Oral Diclofenac on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

    PubMed

    Ishiwatari, Hirotoshi; Urata, Takahiro; Yasuda, Ichiro; Matsusaki, Shimpei; Hisai, Hiroyuki; Kawakami, Hiroshi; Ono, Michihiro; Iwashita, Takuji; Doi, Shinpei; Kawakubo, Kazumichi; Hayashi, Tsuyoshi; Sonoda, Tomoko; Sakamoto, Naoya; Kato, Junji

    2016-11-01

    Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) is a serious complication. Rectal diclofenac (100 mg) has been shown to reduce the incidence of pancreatitis; however, this dosage form is unavailable in several countries. We aimed to investigate the preventive effect of oral diclofenac on pancreatitis after ERCP in a multicenter, randomized, prospective, placebo-controlled, double-blind trial. Patients undergoing a first ERCP in seven high-volume centers between July 2012 and August 2014 were considered eligible. Participants were administered oral diclofenac (50 mg) or placebo before and after ERCP. The primary endpoint was the incidence of pancreatitis. A subgroup analysis was performed for patients at high or low risk of pancreatitis. Secondary endpoints were pancreatic enzyme levels (amylase and lipase). We initially enrolled 430 patients (216 in the diclofenac and 214 in the placebo group), and 23 were excluded after randomization. The overall incidence of pancreatitis was 9.8 % (20/205) and 9.4 % (19/202) in the diclofenac and placebo groups, respectively (p = 0.90). The incidence of pancreatitis was 20.3 % (13/64) and 21.3 % (13/61) in patients at high risk of pancreatitis (p = 0.78) and 5.0 % (7/141) and 4.3 % (6/141) in patients at low risk of pancreatitis in the diclofenac and placebo groups (p = 0.94), respectively. There were no significant differences in serum amylase and lipase levels between the two groups before and 24 h after ERCP. Oral administration of diclofenac before and after ERCP showed no benefit in the prevention of pancreatitis. UMIN000008109.

  6. α-Lipoic acid protects against cholecystokinin-induced acute pancreatitis in rats

    PubMed Central

    Park, Sung-Joo; Seo, Sang-Wan; Choi, Ok-Sun; Park, Cheung-Seog

    2005-01-01

    AIM: α-Lipoic acid (ALA) has been used as an antioxidant. The aim of this study was to investigate the effect of α-lipoic acid on cholecystokinin (CCK)-octapeptide induced acute pancreatitis in rats. METHODS: ALA at 1 mg/kg was intra-peritoneally injected, followed by 75 μg/kg CCK-octapeptide injected thrice subcutaneously after 1, 3, and 5 h. This whole procedure was repeated for 5 d. We checked the pancreatic weight/body weight ratio, the secretion of pro-inflammatory cytokines and the levels of lipase, amylase of serum. Repeated CCK octapeptide treatment resulted in typical laboratory and morphological changes of experimentally induced pancreatitis. RESULTS: ALA significantly decreased the pancreatic weight/body weight ratio and serum amylase and lipase in CCK octapeptide-induced acute pancreatitis. However, the secretion of IL-1β, IL-6, and TNF-α were comparable in CCK octapeptide-induced acute pancreatitis. CONCLUSION: ALA may have a protective effect against CCK octapeptide-induced acute pancreatitis. PMID:16097064

  7. Acute pancreatitis attributed to the use of interferon alfa-2b.

    PubMed

    Eland, I A; Rasch, M C; Sturkenboom, M J; Bekkering, F C; Brouwer, J T; Delwaide, J; Belaiche, J; Houbiers, G; Stricker, B H

    2000-07-01

    Two patients experienced episodes of acute pancreatitis shortly after starting treatment with interferon alfa-2b (IFN-alpha) for a chronic hepatitis C infection. The first patient was a 40-year-old man who developed acute pancreatitis after 15 weeks of treatment with 3 MU IFN-alpha subcutaneously (SC) 3 times weekly and 1200 mg ribavirin. After disappearance of symptoms and normalization of laboratory values, oral intake of solid foods and IFN-alpha therapy were restarted. Within hours, a relapse of acute pancreatitis occurred. A rechallenge with IFN-alpha 4 days later was followed by a prompt increase in serum lipase level, and IFN-alpha therapy was discontinued. The second patient was a 38-year-old man who developed acute pancreatitis 2 hours after SC administration of 5 MU IFN-alpha. Ultrasound endoscopy showed sludge in the gallbladder. The patient was rechallenged 5 weeks later with 3 MU IFN-alpha SC. Although serum amylase and lipase levels increased after readministration of IFN-alpha, treatment was continued. The patient was readmitted 2 weeks later with severe abdominal pain, and IFN-alpha administration was discontinued. Considering the temporal relationship between the start of IFN-alpha treatment and development of acute pancreatitis, the absence of other clear etiologic factors for acute pancreatitis, disappearance of symptoms after discontinuation of IFN-alpha, and positive reactions to rechallenge, IFN-alpha is the most probable cause for development of acute pancreatitis in these patients.

  8. Flavocoxid, a dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis

    PubMed Central

    Polito, F; Bitto, A; Irrera, N; Squadrito, F; Fazzari, C; Minutoli, L; Altavilla, D

    2010-01-01

    BACKGROUND AND PURPOSE Acute pancreatitis is an autodigestive process resulting in acute inflammation of the pancreas. Accumulating evidence indicates the essential contribution of cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) to acute pancreatitis. We studied the effects of flavocoxid, a plant-derived dual inhibitor of COX-2 and 5-LOX, in a model of caerulein (CER)-induced acute pancreatitis. EXPERIMENTAL APPROACH Rats were given CER (80 µg·kg−1 for each of four injections at hourly intervals) or vehicle (Sham-CER). Animals were then randomized to receive flavocoxid (20 mg·kg−1 i.p.) or vehicle, 30 min after the first CER injection. Two hours after the last CER injection, we evaluated damage to the pancreas by histological methods; serum levels of amylase, lipase, leukotriene (LT)B4 and prostaglandin (PG)E2; pancreatic expression of COX-2 and 5-LOX and tumour necrosis factor-α (TNF-α) gene expression by real-time polymerase chain reaction. KEY RESULTS Caerulein induced inflammatory changes in the pancreas and raised values of the other variables measured. In CER-treated animals, but not in those given saline, flavocoxid inhibited COX-2 and 5-LOX expression, reduced serum levels of lipase and amylase and the degree of pancreatic oedema. Treatment with flavocoxid blunted the increased pancreatic TNF-α mRNA expression, serum leukotriene B4 and prostaglandin E2 levels, and protected against histological damage in terms of vacuolization and leukocyte infiltration. CONCLUSIONS AND IMPLICATIONS Our results confirm the key role of both COX-2 and 5-LOX in the inflammatory response to acute pancreatitis. Flavocoxid may provide a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition. PMID:20977452

  9. Flavocoxid, a dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis.

    PubMed

    Polito, F; Bitto, A; Irrera, N; Squadrito, F; Fazzari, C; Minutoli, L; Altavilla, D

    2010-11-01

    Acute pancreatitis is an autodigestive process resulting in acute inflammation of the pancreas. Accumulating evidence indicates the essential contribution of cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) to acute pancreatitis. We studied the effects of flavocoxid, a plant-derived dual inhibitor of COX-2 and 5-LOX, in a model of caerulein (CER)-induced acute pancreatitis. Rats were given CER (80 µg·kg⁻¹ for each of four injections at hourly intervals) or vehicle (Sham-CER). Animals were then randomized to receive flavocoxid (20 mg·kg⁻¹ i.p.) or vehicle, 30 min after the first CER injection. Two hours after the last CER injection, we evaluated damage to the pancreas by histological methods; serum levels of amylase, lipase, leukotriene (LT)B₄ and prostaglandin (PG)E₂ ; pancreatic expression of COX-2 and 5-LOX and tumour necrosis factor-α (TNF-α) gene expression by real-time polymerase chain reaction. Caerulein induced inflammatory changes in the pancreas and raised values of the other variables measured. In CER-treated animals, but not in those given saline, flavocoxid inhibited COX-2 and 5-LOX expression, reduced serum levels of lipase and amylase and the degree of pancreatic oedema. Treatment with flavocoxid blunted the increased pancreatic TNF-α mRNA expression, serum leukotriene B₄ and prostaglandin E₂ levels, and protected against histological damage in terms of vacuolization and leukocyte infiltration. Our results confirm the key role of both COX-2 and 5-LOX in the inflammatory response to acute pancreatitis. Flavocoxid may provide a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

  10. Lipase

    MedlinePlus

    ... used for indigestion, heartburn, allergy to gluten in wheat products (celiac disease), Crohn's disease, and cystic fibrosis. ... associated with cystic fibrosis.Allergy to gluten in wheat products (celiac disease). Crohn's disease. Indigestion. Heartburn. Other ...

  11. Synthesis of oleoylethanolamide using lipase.

    PubMed

    Wang, Xiaosan; Wang, Xingguo; Wang, Tong

    2012-01-11

    An effective process for the enzymatic synthesis of oleoylethanolamide is described in this study. The process included purification of a commercial oleic acid product and then optimization of the reaction between the purified oleic acid and ethanolamine in the presence of hexane and a lipase. Under the optimal amidation reaction conditions identified, oleoylethanolamide was obtained with 96.6% purity. The synthesis was also conducted on a large scale (50 mmol of each of the reactants), and oleoylethanolamide purity and yield after crystallization purification were 96.1 and 73.5%, respectively. Compared to the previous studies, the current method of preparing high-purity oleoylethanolamide is more effective and economically feasible. The scalability and ease for such synthesis make it possible to study the biological and nutritional functions of the cannabinoid-like oleoylethanolamide in animal or human subjects.

  12. Is Pancreatic Cancer Hereditary?

    MedlinePlus

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

  13. Genetics Home Reference: hepatic lipase deficiency

    MedlinePlus

    ... affects the body's ability to break down fats (lipids). People with this disorder have increased amounts of ... It is unclear what effect this change in lipid levels has on people with hepatic lipase deficiency . ...

  14. Genetics Home Reference: lysosomal acid lipase deficiency

    MedlinePlus

    ... Cegielska J, Whitley CB, Eckert S, Valayannopoulos V, Quinn AG. Clinical Features of Lysosomal Acid Lipase Deficiency. J ... qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Subscribe Customer Support USA. ...

  15. Quantitative study of digestive enzyme secretion and gastrointestinal lipolysis in chronic pancreatitis.

    PubMed

    Carrière, Frédéric; Grandval, Philippe; Renou, Christophe; Palomba, Aurélie; Priéri, Florence; Giallo, Jacqueline; Henniges, Friederike; Sander-Struckmeier, Suntje; Laugier, René

    2005-01-01

    The contribution of human gastric lipase (HGL) to the overall lipolysis process in chronic pancreatitis (CP), as well as the relative pancreatic enzyme levels, rarely are addressed. This study was designed to quantify pancreatic and extrapancreatic enzyme output, activity, and stability in CP patients vs. healthy volunteers. Healthy volunteers (n = 6), mild CP patients (n = 5), and severe (n = 7) CP patients were intubated with gastric and duodenal tubes before the administration of a test meal. HGL, human pancreatic lipase (HPL), chymotrypsin, and amylase concentrations were assessed in gastric and duodenal samples by measuring the respective enzymatic activities. Intragastric and overall lipolysis levels at the angle of Treitz were estimated based on quantitative analysis of lipolysis products. Similar analyses were performed on duodenal contents incubated ex vivo for studying enzyme stability and evolution of lipolysis. Although HPL, chymotrypsin, and amylase outputs all were extremely low, HGL outputs in patients with severe CP (46.8 +/- 31.0 mg) were 3-4-fold higher than in healthy controls (13.3 +/- 13.8 mg). Intragastric lipolysis did not increase, however, in patients with severe CP, probably because of the rapid decrease in the pH level of the gastric contents caused by a higher gastric acid secretion. HGL remains active and highly stable in the acidic duodenal contents of CP patients, and, overall, can achieve a significant lipolysis of the dietary triglycerides (30% of the control values) in the absence of HPL. Although all pancreatic enzyme secretions are simultaneously reduced in severe CP, gastric lipase can compensate partly for the loss of pancreatic lipase but not normalize overall lipolytic activity.

  16. Neutrophil chemotaxis by Propionibacterium acnes lipase and its inhibition.

    PubMed Central

    Lee, W L; Shalita, A R; Suntharalingam, K; Fikrig, S M

    1982-01-01

    The chemoattraction of Propionibacterium acnes lipase for neutrophils and the effect of lipase inhibitor and two antibiotic agents on the chemotaxis were evaluated. Of the various fractions tested, partially purified lipase (fraction 2c) was the most active cytotaxin produced by P. acnes. Serum mediators were not required for the generation of chemotaxis by lipase in vitro. Diisopropyl phosphofluoridate at low concentration (10(-4) mM) completely inhibited lipase activity as well as polymorphonuclear leukocyte chemotaxis generated by lipase. Tetracycline hydrochloride and erythromycin base at concentrations of 10(-1) mM and 1 mM, respectively, caused 100% inhibition of PMN migration toward lipase or zymosan-activated serum. The inhibiting activity of the antibiotics was directed against cells independently of any effect on lipase. Chemotaxis by P. acnes lipase suggests a wider role for this enzyme in the inflammatory process and the pathogenesis of acne vulgaris. Images PMID:7054130

  17. Extract of grapefruit-seed reduces acute pancreatitis induced by ischemia/reperfusion in rats: possible implication of tissue antioxidants.

    PubMed

    Dembinski, A; Warzecha, Z; Konturek, S J; Ceranowicz, P; Dembinski, M; Pawlik, W W; Kusnierz-Cabala, B; Naskalski, J W

    2004-12-01

    Grapefruit seed extract (GSE) has been shown to exert antibacterial, antifungal and antioxidant activity possibly due to the presence of naringenin, the flavonoid with cytoprotective action on the gastric mucosa. No study so far has been undertaken to determine whether this GSE is also capable of preventing acute pancreatic damage induced by ischemia/reperfusion (I/R), which is known to result from reduction of anti-oxidative capability of pancreatic tissue, and whether its possible preventive effect involves an antioxidative action of this biocomponent. In this study carried out on rats with acute hemorrhagic pancreatitis induced by 30 min partial pancreatic ischemia followed by 6 h of reperfusion, the GSE or vehicle (vegetable glycerin) was applied intragastrically in gradually increasing amounts (50-500 microl) 30 min before I/R. Pretreatment with GSE decreased the extent of pancreatitis with maximal protective effect of GSE at the dose 250 microl. GSE reduced the pancreatitis-evoked increase in serum lipase and poly-C specific ribonuclease activity, and attenuated the marked fall in pancreatic blood flow and pancreatic DNA synthesis. GSE administered alone increased significantly pancreatic tissue content of lipid peroxidation products, malondialdehyde and 4-hydroxyalkens, and when administered before I/R, GSE reduced the pancreatitis-induced lipid peroxidation. We conclude that GSE exerts protective activity against I/R-induced pancreatitis probably due to the activation of antioxidative mechanisms in the pancreas and the improvement of pancreatic blood flow.

  18. [Mediastinal Pancreatic Pseudocyst with Pancreatic Pleural Effusion].

    PubMed

    Sasajima, Motoko; Kawai, Hideki; Suzuki, Yohei; Saito, Yoshitaro; Eto, Takeshi

    2017-06-01

    A 72-year-old man with chronic alcohol related pancreatitis was admitted for dyspnea and pain at the upper body. Chest X-ray showed right massive pleural effusion. Chest and abdominal contrast enhanced thin slice computed tomography revealed the route from the pancreatic head reaching the right thoracic cavity via the esophagus hiatus and the communication between the cystic lesion and main pancreatic duct. We drained the pleural effusion that showed abnormally high amylase activity. We diagnosed his illness as mediastinal pancreatic pseudocyst with pancreatic pleural effusion. Endoscopic Nasopancreatic Drainage catheter was placed in the main pancreatic duct, and the pleural effusion disappeared.

  19. Isolated immune-related pancreatic exocrine insufficiency associated with pembrolizumab therapy.

    PubMed

    Prasanna, Thiru; McNeil, Catriona M; Nielsen, Theresa; Parkin, David

    2018-03-01

    We report a case of isolated immune-related pancreatic exocrine insufficiency in a patient treated with pembrolizumab for metastatic melanoma. This patient presented with explosive diarrhea and was treated with high dose corticosteroids for possible immune-related colitis. However, biopsies from colon and duodenum did not show any histological evidence of colitis/enteritis. Serum amylase and lipase were not elevated. There was no evidence of pancreatitis or pancreatic metastases on imaging. Significantly lower fecal elastase test on two occasions confirmed the diagnosis of pancreatic exocrine insufficiency. He was treated with pancreatic enzyme supplementation with complete resolution of diarrhea. This case reinforces the importance of awareness and anticipation of unusual immune-related adverse events related to checkpoint inhibitors.

  20. Protective effects of tropisetron on cerulein-induced acute pancreatitis in mice.

    PubMed

    Rahimian, Reza; Zirak, Mohammad Reza; Seyedabadi, Mohammad; Keshavarz, Mojtaba; Rashidian, Amir; Kazmi, Sareh; Jafarian, Amir Hossein; Karimi, Gholamreza; Mousavizadeh, Kazem

    2017-09-01

    Acute pancreatitis (AP) causes morbidity and mortality. The aim of the present study was to investigate the protective effect of tropisetron against AP induced by cerulein. Cerulein (50μg/kg, 5 doses) was used to induce AP in mice. Six hours after final cerulein injection, animals were decapitated. Hepatic/pancreatic enzymes in the serum, pancreatic content of malondialdehyde (MDA), pro-inflammatory cytokines and myeloperoxidase (MPO) activity were measured. Tropisetron significantly attenuated pancreatic injury markers and decreased the amount of elevated serum amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), MPO activities and pro-inflammatory cytokines levels caused by AP in mice. Tropisetron didn't affect the pancreatic levels of MDA. Our results suggest that tropisetron could attenuate cerulein-induced AP by combating inflammatory signaling. Further clinical studies are needed to confirm its efficacy in patients with AP. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Acute Lipotoxicity Regulates Severity of Biliary Acute Pancreatitis without Affecting Its Initiation

    PubMed Central

    Durgampudi, Chandra; Noel, Pawan; Patel, Krutika; Cline, Rachel; Trivedi, Ram N.; DeLany, James P.; Yadav, Dhiraj; Papachristou, Georgios I.; Lee, Kenneth; Acharya, Chathur; Jaligama, Deepthi; Navina, Sarah; Murad, Faris; Singh, Vijay P.

    2015-01-01

    Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O–positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate–induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction. PMID:24854864

  2. Comparison of lipases for in vitro models of gastric digestion: lipolysis using two infant formulas as model substrates.

    PubMed

    Sassene, P J; Fanø, M; Mu, H; Rades, T; Aquistapace, S; Schmitt, B; Cruz-Hernandez, C; Wooster, T J; Müllertz, A

    2016-09-14

    The aim of this study was to find a lipase suitable as a surrogate for Human Gastric Lipase (HGL), since the development of predictive gastrointestinal lipolysis models are hampered by the lack of a lipase with similar digestive properties as HGL. Three potential surrogates for HGL; Rhizopus Oryzae Lipase (ROL), Rabbit Gastric Lipase (RGL) and recombinant HGL (rHGL), were used to catalyze the in vitro digestion of two infant formulas (a medium-chain triacylglyceride enriched formula (MC-IF) and a predominantly long-chain triacylglyceride formula (LC-IF)). Digesta were withdrawn after 0, 5, 15, 30, 60 min of gastric digestion and after 90 or 180 min of intestinal digestion with or without the presence of pancreatic enzymes, respectively. The digesta were analyzed by scanning electron microscopy and gas chromatography to quantify the release of fatty acids (FAs). Digestions of both formulas, catalyzed by ROL, showed that the extent of gastric digestion was higher than expected from previously published in vivo data. ROL was furthermore insensitive to FA chain length and all FAs were released at the same pace. RGL and rHGL favoured the release of MC-FAs in both formulas, but rHGL did also release some LC-FAs during digestion of MC-IF, whereas RGL only released MC-FAs. Digestion of a MC-IF by HGL in vivo showed that MC-FAs are preferentially released, but some LC-FAs are also released. Thus of the tested lipase rHGL replicated the digestive properties of HGL the best and is a suitable surrogate for HGL for use in in vitro gastrointestinal lipolysis models.

  3. Effects of porcine pancreatic enzymes on the pancreas of hamsters. Part 2: carcinogenesis studies.

    PubMed

    Nozawa, Fumiaki; Yalniz, Mehmet; Saruc, Murat; Standop, Jens; Egami, Hiroshi; Pour, Parviz M

    2012-09-10

    Our previous study suggested that porcine pancreatic extract in hamsters with peripheral insulin resistance, normalizes insulin output, islet size and pancreatic DNA synthetic rate. It also inhibited the growth of human pancreatic cancer cells in nude mice. To examine the potential value of the porcine pancreatic extract in controlling pancreatic carcinogenesis in this model, the present experiment was performed. Hamsters were fed a high fat diet and four weeks later when insulin resistance emerges, they were divided into two groups. One group received 1 g/kg BW of porcine pancreatic extract in drinking water and the other group received tap water. One week later, when insulin output normalizes in porcine pancreatic extract-treated hamsters, a single subcutaneous injection of N-nitrosobis-(2-oxopropyl) amine (BOP) at a dose of 40 mg/kg BW was given to all hamsters. The experiment was terminated at 43 weeks after the porcine pancreatic extract treatment. The number and size of pancreatic tumors, blood glucose, insulin, amylase and lipase levels, the average size of islets and the number of insulin cells/islets were determined. The incidence of pancreatic cancer was significantly lower in the porcine pancreatic extract group (P=0.043), as well as the plasma insulin level and the size of the islets in the porcine pancreatic extract group were significantly lower (P<0.001) than in the control group. No significantly differences were found in the glucose level between the groups. These results show that porcine pancreatic extract has a potential to inhibit pancreatic cancer growth.

  4. Utility of serum pancreatic enzyme levels in diagnosing blunt trauma to the pancreas: a prospective study with systematic review.

    PubMed

    Mahajan, Abhishek; Kadavigere, Rajagopal; Sripathi, Smiti; Rodrigues, Gabriel Sunil; Rao, Vedula Rajanikanth; Koteshwar, Prakashini

    2014-09-01

    Reliability of serum pancreatic enzyme levels in predicting pancreatic injuries has been a parameter of interest and the present recommendations on its utility are based primarily on anecdotal observations. The aim of this study was to evaluate the utility of serum pancreatic enzyme assessment in predicting blunt pancreatic injury with imaging and surgical correlation and compare our results with a systematic review of literature till date. A prospective cohort study conducted over 4 years in a tertiary care referral centre with 164 consecutive patients who presented to the emergency department with a history of blunt abdominal trauma and had serum pancreatic enzyme assessment, USG and subsequent diagnostic CECT were analyzed. The CT findings and AAST grade of pancreatic injury, various intra-abdominal injuries and time elapsed since injury and other associated factors were correlated with serum pancreatic enzyme levels. For systematic review of literature MEDLINE database was searched between 1940 and 2012, also the related citations and bibliographies of relevant articles were analyzed and 40 articles were included for review. We compared our results with the systematic critique of literature till date to formulate recommendations. 33(21%) patients had pancreatic injury documented on CT and were graded according to AAST. Statistically significant elevated serum amylase levels were observed in patients with pancreatic and bowel injuries. However, elevated serum lipase was observed specifically in patients with pancreatic injury with or without bowel injury. Combined serum amylase and lipase showed 100% specificity, 85% sensitivity in predicting pancreatic injury. Elevated (n=28, 85%) vs. normal (n=5, 15%) serum amylase and lipase levels showed sole statistically significant association with time elapse since injury to admission, with a cutoff of 3h. Based on our results and the systematic review of the literature till date we conclude, persistently elevated or

  5. Korean red ginseng ameliorated experimental pancreatitis through the inhibition of hydrogen sulfide in mice.

    PubMed

    Lee, Sooyeon; Park, Jong-Min; Jeong, Migyeong; Han, Young-Min; Go, Eun Jin; Ko, Weon Jin; Cho, Joo Young; Kwon, Chang Il; Hahm, Ki Baik

    2016-01-01

    Effective therapy to treat acute pancreatitis (AP) or to prevent its recurrence/complication is still not available. Based on previous results that suggest that: i) hydrogen sulfide (H2S) levels were significantly increased in pancreatitis and gastritis and ii) Korean red ginseng (KRG) efficiently attenuated Helicobacter pylori-associated gastritis through the suppressive actions of H2S, we hypothesized that KRG can ameliorate experimental pancreatitis through suppression of H2S generation. C57BL/6 mice were pre-administered KRG and then subjected to cerulein injection or pancreatic duct ligation (PDL) to induce pancreatitis. Blood and pancreas tissues were collected and processed to measure serum levels of amylase, lipase and myeloperoxidase and the concentration of H2S and the levels of various inflammatory cytokine in pancreatic tissues of mice with induced AP. KRG significantly inhibited NaHS-induced COX-2 and TNF-α mRNA in pancreatic cells, but dl-propargylglycine did not. KRG ameliorated cerulein-induced edematous pancreatitis accompanied with significant inactivation of NF-κB and JNK in pancreatic tissues of C57BL/6 mice (p < 0.001) and also significantly ameliorated PDL-induced necrotizing pancreatitis (p<0.01); in both conditions, the significant suppression of H2S resulting from KRG pretreatment afforded rescuing outcomes. Along with suppressed levels of H2S consequent to depressed expressions of CBS and CSE mRNA, KRG administration efficiently decreased the serum level of amylase, lipase, and myeloperoxidase and the expression of inflammatory cytokines in animal models of mild or severe AP. These results provide evidence for the preventive and therapeutic roles of KRG against AP mediated by H2S suppression. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  6. Identification and characterization of a triacylglycerol lipase in Arabidopsis homologous to mammalian acid lipases.

    PubMed

    El-Kouhen, Karim; Blangy, Stéphanie; Ortiz, Emilia; Gardies, Anne-Marie; Ferté, Natalie; Arondel, Vincent

    2005-11-07

    Triacylglycerol (TAG) lipases have been thoroughly characterized in mammals and microorganisms. By contrast, very little is known on plant TAG lipases. An Arabidopsis cDNA called AtLip1 (At2g15230), which exhibits strong homology to lysosomal acid lipase, was found to drive the synthesis of an active TAG lipase when expressed in the baculovirus system. The lipase had a maximal activity at pH 6 and the specific activity was estimated to be about 45 micromol min(-1) mg(-1) protein using triolein as a substrate. Knock-out mutant analysis showed no phenotype during germination indicating that this enzyme is fully dispensable for TAG storage breakdown during germination. Northern blot analyses indicated that the transcript is present in all tissues tested.

  7. Evaluation of amylase and lipase levels in blunt trauma abdomen patients.

    PubMed

    Kumar, Subodh; Sagar, Sushma; Subramanian, Arulselvi; Albert, Venencia; Pandey, Ravindra Mohan; Kapoor, Nitika

    2012-04-01

    There are studies to prove the role of amylase and lipase estimation as a screening diagnostic tool to detect diseases apart from acute pancreatitis. However, there is sparse literature on the role of serum and urine amylase, lipase levels, etc to help predict the specific intra-abdominal injury after blunt trauma abdomen (BTA). To elucidate the significance of elevation in the levels of amylase and lipase in serum and urine samples as reliable parameters for accurate diagnosis and management of blunt trauma to the abdomen. A prospective analysis was done on the trauma patients admitted in Jai Prakash Narayan Apex Trauma Center, AIIMS, with blunt abdomen trauma injuries over a period of six months. Blood and urine samples were collected on days 1, 3, and 5 of admission for the estimation of amylase and lipase, liver function tests, serum bicarbonates, urine routine microscopy for red blood cells, and complete hemogram. Clinical details such as time elapsed from injury to admission, type of injury, trauma score, and hypotension were noted. Patients were divided into groups according to the single or multiple organs injured and according to their hospital outcome (dead/discharged). Wilcoxon's Rank sum or Kruskal-Wallis tests were used to compare median values in two/three groups. Data analysis was performed using STATA 11.0 statistical software. A total of 55 patients with median age 26 (range, 6-80) years, were enrolled in the study. Of these, 80% were males. Surgery was required for 20% of the patients. Out of 55 patients, 42 had isolated single organ injury [liver or spleen or gastrointestinal tract (GIT) or kidney]. Patients with pancreatic injury were excluded. In patients who suffered liver injuries, urine lipase levels on day 1, urine lipase/amylase ratio along with aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) on days 1, 3, and 5, were found to be significant. Day 1 serum amylase, AST, ALT, hemoglobin, and

  8. Evaluation of amylase and lipase levels in blunt trauma abdomen patients

    PubMed Central

    Kumar, Subodh; Sagar, Sushma; Subramanian, Arulselvi; Albert, Venencia; Pandey, Ravindra Mohan; Kapoor, Nitika

    2012-01-01

    Background: There are studies to prove the role of amylase and lipase estimation as a screening diagnostic tool to detect diseases apart from acute pancreatitis. However, there is sparse literature on the role of serum and urine amylase, lipase levels, etc to help predict the specific intra-abdominal injury after blunt trauma abdomen (BTA). Aim: To elucidate the significance of elevation in the levels of amylase and lipase in serum and urine samples as reliable parameters for accurate diagnosis and management of blunt trauma to the abdomen. Materials and Methods: A prospective analysis was done on the trauma patients admitted in Jai Prakash Narayan Apex Trauma Center, AIIMS, with blunt abdomen trauma injuries over a period of six months. Blood and urine samples were collected on days 1, 3, and 5 of admission for the estimation of amylase and lipase, liver function tests, serum bicarbonates, urine routine microscopy for red blood cells, and complete hemogram. Clinical details such as time elapsed from injury to admission, type of injury, trauma score, and hypotension were noted. Patients were divided into groups according to the single or multiple organs injured and according to their hospital outcome (dead/discharged). Wilcoxon's Rank sum or Kruskal–Wallis tests were used to compare median values in two/three groups. Data analysis was performed using STATA 11.0 statistical software. Results: A total of 55 patients with median age 26 (range, 6-80) years, were enrolled in the study. Of these, 80% were males. Surgery was required for 20% of the patients. Out of 55 patients, 42 had isolated single organ injury [liver or spleen or gastrointestinal tract (GIT) or kidney]. Patients with pancreatic injury were excluded. In patients who suffered liver injuries, urine lipase levels on day 1, urine lipase/amylase ratio along with aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) on days 1, 3, and 5, were found to be significant

  9. Morphological and functional alterations of small intestine in chronic pancreatitis.

    PubMed

    Gubergrits, Natalya B; Linevskiy, Yuri V; Lukashevich, Galina M; Fomenko, Pavel G; Moroz, Tatyana V; Mishra, Tapan

    2012-09-10

    The small intestine in chronic pancreatitis has not been investigated yet thoroughly. It would be important to understand fat metabolism in the course of this disease and could be explained if the small intestine has some pathological conditions and, due to this reason, pancreatic enzyme substitution does not work in all patients. To investigate the pathophysiology of small intestine in chronic pancreatitis and to show the reason why in some cases pancreatic enzyme substitution does not work properly. In the process of the study 33 chronic pancreatitis patients have been examined. The control group includes 30 subjects without chronic pancreatitis similar for age, sex and alcohol consumption to the patients with chronic pancreatitis patients. Aspiration biopsy of jejunum mucosa followed by histological examination and investigation of intestinal enzymes by aspiration has been performed. Metabolism at membranic level has been studied by enzymatic activity of amylase and lipase in the small intestine. Production of enzymes (monoglyceride lipase, lactase, saccharase, maltase, glycyl-l-leucine dipeptidase) promoting metabolism in enterocytes has been estimated as to their activity in homogenates of jejunum mucosa samples. Participation of mucosa in intestinal digestion has been assessed by alkaline phosphatase activity in a secretory chyme from proximal portion of jejunum. Absorptive capacity of jejunum was evaluated by D-xylose test results. DNA, lysozyme, immunoglobulin contents of chyme have also been calculated and bacteriological study of chyme has been also performed. Secondary enteritis, accompanied by moderate dystrophic changes of mucous membrane, thinning of limbus, and decrease of Paneth cell mitotic index, was found to occur in chronic pancreatitis patients. Enteritis is followed by changes in enzymatic processes in the sphere of membrane and intestinal digestion, decrease of absorption, accelerated desquamation of epithelium, fall in local immunity and

  10. Severe hypertriglyceridemia with pancreatitis: thirteen years' treatment with lomitapide.

    PubMed

    Sacks, Frank M; Stanesa, Maxine; Hegele, Robert A

    2014-03-01

    Recurrent pancreatitis is a potentially fatal complication of severe hypertriglyceridemia. Genetic defects and lifestyle risk factors may render this condition unresponsive to current treatments. We report this first case of long-term management of intractable near-fatal recurrent pancreatitis secondary to severe hypertriglyceridemia by a novel use of lomitapide, an inhibitor of microsomal triglyceride transfer protein, recently approved for treatment of familial homozygous hypercholesterolemia. The patient had been hospitalized many times for pancreatitis since age 15 years. Her serum triglyceride level averaged 3900 mg/dL while she received therapy with approved lipid drugs. She is homozygous for a coding mutation (P234L) in lipoprotein lipase, leaving her unable to metabolize triglycerides in chylomicrons and very low density lipoproteins (VLDL). Lomitapide reduces the secretion of chylomicrons and VLDL. Lomitapide, which was started when she was 44 years old after near-fatal pancreatitis, lowered her fasting triglyceride level from greater than 3000 mg/dL to a mean (SD) of 903 (870) mg/dL while she received 30 mg/d and to 524 (265) mg/dL while she received 40 mg/d; eliminated chronic abdominal pain; and prevented pancreatitis. However, fatty liver, present before treatment, progressed to steatohepatitis and fibrosis after 12 to 13 years. Lomitapide prevented pancreatitis in severe intractable hypertriglyceridemia but at a potential long-term cost of hepatotoxicity.

  11. Autoimmune pancreatitis can develop into chronic pancreatitis

    PubMed Central

    2014-01-01

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

  12. The epidemiology of pancreatitis and pancreatic cancer.

    PubMed

    Yadav, Dhiraj; Lowenfels, Albert B

    2013-06-01

    Acute pancreatitis is one of the most frequent gastrointestinal causes of hospital admission in the United States. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreatic cancer is associated with a high mortality rate and is one of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect the black population more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  13. Autoimmune pancreatitis can develop into chronic pancreatitis.

    PubMed

    Maruyama, Masahiro; Watanabe, Takayuki; Kanai, Keita; Oguchi, Takaya; Asano, Jumpei; Ito, Tetsuya; Ozaki, Yayoi; Muraki, Takashi; Hamano, Hideaki; Arakura, Norikazu; Kawa, Shigeyuki

    2014-05-21

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

  14. The Epidemiology of Pancreatitis and Pancreatic Cancer

    PubMed Central

    Yadav, Dhiraj; Lowenfels, Albert B.

    2013-01-01

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

  15. Options for addressing exocrine pancreatic insufficiency in patients receiving enteral nutrition supplementation.

    PubMed

    Freedman, Steven D

    2017-07-01

    Patients with exocrine pancreatic insufficiency (EPI) have suboptimal secretion of pancreatic digestive enzymes and experience a range of clinical symptoms related to the malabsorption of fat. In patients with EPI unable to meet their nutritional requirements, enteral nutrition (EN) support is used to augment nutritional status. In addition to protein and carbohydrate, EN formulas contain fats as a calorie source, as well as vitamins and minerals to help prevent nutritional deficiencies related to malabsorption. Semielemental enteral nutrition formulas are advantageous as they contain hydrolyzed protein, shorter chain carbohydrates, and may contain medium chain triglycerides as a fat source. However, severely pancreatic insufficient patients may be unable to absorb complex long-chain triglycerides provided by EN formulas due to insufficient pancreatic lipase; replacement pancreatic enzyme products are recommended for these patients. Currently, none of the FDA-approved pancreatic enzyme replacement therapy (PERT) products are indicated for use in patients receiving enteral nutrition and administration of enzymes by mixing into enteral nutrition formula is not supported by guidelines as this route is associated with risks. RELiZORB (immobilized lipase) is a novel in-line digestive cartridge that has been designed to address the unmet need for PERT in patients receiving enteral nutrition. RELiZORB efficacy and compatibility with a range of commercially available polymeric and semielemental formulas with varying nutrient, caloric content, and triglyceride chain lengths have been demonstrated. In most formulas, RELiZORB efficiently hydrolyzed greater than 90% of fats within the formula into absorbable fatty acids and monoglycerides.

  16. Monoacylglycerol Lipase Regulates Fever Response

    PubMed Central

    Sanchez-Alavez, Manuel; Nguyen, William; Mori, Simone; Moroncini, Gianluca; Viader, Andreu; Nomura, Daniel K.; Cravatt, Benjamin F.; Conti, Bruno

    2015-01-01

    Cyclooxygenase inhibitors such as ibuprofen have been used for decades to control fever through reducing the levels of the pyrogenic lipid transmitter prostaglandin E2 (PGE2). Historically, phospholipases have been considered to be the primary generator of the arachidonic acid (AA) precursor pool for generating PGE2 and other eicosanoids. However, recent studies have demonstrated that monoacyglycerol lipase (MAGL), through hydrolysis of the endocannabinoid 2-arachidonoylglycerol, provides a major source of AA for PGE2 synthesis in the mammalian brain under basal and neuroinflammatory states. We show here that either genetic or pharmacological ablation of MAGL leads to significantly reduced fever responses in both centrally or peripherally-administered lipopolysaccharide or interleukin-1β-induced fever models in mice. We also show that a cannabinoid CB1 receptor antagonist does not attenuate these anti-pyrogenic effects of MAGL inhibitors. Thus, much like traditional nonsteroidal anti-inflammatory drugs, MAGL inhibitors can control fever, but appear to do so through restricted control over prostaglandin production in the nervous system. PMID:26287872

  17. MIF Drives Pancreatic Cancer Aggressiveness by Downregulating NR3C2 | Center for Cancer Research

    Cancer.gov

    Pancreatic cancer, while relatively rare, is an aggressive disease ranked as the fourth leading cause of cancer-related death in the US. Because most patients are diagnosed at an advanced stage and their tumors resist available treatments, novel therapeutic targets are urgently needed. Macrophage Migration Inhibitory Factor (MIF) is a proinflammatory cytokine that is elevated in pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, and may provide a molecular link between inflammation and cancer, though the mechanism is unknown.

  18. Realm of Thermoalkaline Lipases in Bioprocess Commodities.

    PubMed

    Lajis, Ahmad Firdaus B

    2018-01-01

    For decades, microbial lipases are notably used as biocatalysts and efficiently catalyze various processes in many important industries. Biocatalysts are less corrosive to industrial equipment and due to their substrate specificity and regioselectivity they produced less harmful waste which promotes environmental sustainability. At present, thermostable and alkaline tolerant lipases have gained enormous interest as biocatalyst due to their stability and robustness under high temperature and alkaline environment operation. Several characteristics of the thermostable and alkaline tolerant lipases are discussed. Their molecular weight and resistance towards a range of temperature, pH, metal, and surfactants are compared. Their industrial applications in biodiesel, biodetergents, biodegreasing, and other types of bioconversions are also described. This review also discusses the advance of fermentation process for thermostable and alkaline tolerant lipases production focusing on the process development in microorganism selection and strain improvement, culture medium optimization via several optimization techniques (i.e., one-factor-at-a-time, surface response methodology, and artificial neural network), and other fermentation parameters (i.e., inoculums size, temperature, pH, agitation rate, dissolved oxygen tension (DOT), and aeration rate). Two common fermentation techniques for thermostable and alkaline tolerant lipases production which are solid-state and submerged fermentation methods are compared and discussed. Recent optimization approaches using evolutionary algorithms (i.e., Genetic Algorithm, Differential Evolution, and Particle Swarm Optimization) are also highlighted in this article.

  19. Realm of Thermoalkaline Lipases in Bioprocess Commodities

    PubMed Central

    2018-01-01

    For decades, microbial lipases are notably used as biocatalysts and efficiently catalyze various processes in many important industries. Biocatalysts are less corrosive to industrial equipment and due to their substrate specificity and regioselectivity they produced less harmful waste which promotes environmental sustainability. At present, thermostable and alkaline tolerant lipases have gained enormous interest as biocatalyst due to their stability and robustness under high temperature and alkaline environment operation. Several characteristics of the thermostable and alkaline tolerant lipases are discussed. Their molecular weight and resistance towards a range of temperature, pH, metal, and surfactants are compared. Their industrial applications in biodiesel, biodetergents, biodegreasing, and other types of bioconversions are also described. This review also discusses the advance of fermentation process for thermostable and alkaline tolerant lipases production focusing on the process development in microorganism selection and strain improvement, culture medium optimization via several optimization techniques (i.e., one-factor-at-a-time, surface response methodology, and artificial neural network), and other fermentation parameters (i.e., inoculums size, temperature, pH, agitation rate, dissolved oxygen tension (DOT), and aeration rate). Two common fermentation techniques for thermostable and alkaline tolerant lipases production which are solid-state and submerged fermentation methods are compared and discussed. Recent optimization approaches using evolutionary algorithms (i.e., Genetic Algorithm, Differential Evolution, and Particle Swarm Optimization) are also highlighted in this article. PMID:29666707

  20. The Role of Pancreatic Enzyme Replacement Therapy in Unresectable Pancreatic Cancer: A Prospective Cohort Study.

    PubMed

    Saito, Tomotaka; Hirano, Kenji; Isayama, Hiroyuki; Nakai, Yousuke; Saito, Kei; Umefune, Gyotane; Akiyama, Dai; Watanabe, Takeo; Takagi, Kaoru; Hamada, Tsuyoshi; Takahara, Naminatsu; Uchino, Rie; Mizuno, Suguru; Kogure, Hirofumi; Matsubara, Saburo; Yamamoto, Natsuyo; Tada, Minoru; Koike, Kazuhiko

    2017-03-01

    Although patients with pancreatic cancer (PC) are prone to exocrine pancreatic insufficiency, there are little evidence about pancreatic enzyme replacement therapy (PERT) in patients with PC, especially those receiving chemotherapy. This is a prospective consecutive observational study of PERT in patients with unresectable PC. We prospectively enrolled patients receiving chemotherapy for unresectable PC from April 2012 to February 2014 and prescribed oral pancrelipase of 48,000 lipase units per meal (pancrelipase group). N-benzoyl-tryrosyl para-aminobenzoic acid test was performed at baseline. Patients receiving chemotherapy before April 2012 were retrospectively studied as a historical cohort. Data on the nutritional markers at baseline and 16 weeks were extracted, and serial changes, defined as the ratio of markers at 16 weeks/baseline, were compared between 2 groups. A total of 91 patients (46 in the pancrelipase group and 45 in the historical cohort) were analyzed. N-benzoyl-tryrosyl para-aminobenzoic acid test was low in 94% of the pancrelipase group. Serial change in the pancrelipase group versus historical cohort was 1.01 versus 0.95 in body mass index (P < 0.001) and 1.03 versus 0.97 in serum albumin (P = 0.131). The rate of exocrine pancreatic insufficiency in unresectable PC was high, and PERT can potentially improve the nutritional status during chemotherapy.

  1. The Proteomic Analysis of Pancreatic Exocrine Insufficiency Protein Marker in Type 2 Diabetes Mellitus Patients

    NASA Astrophysics Data System (ADS)

    Srihardyastutie, Arie; Soeatmadji, DW; Fatchiyah; Aulanni'am

    2018-01-01

    Type 2 Diabetes Mellitus (T2D) is the vast majority case of diabetes. Patient with T2D is at higher risk for developing acute or chronic pancreatitis. Prolonged hyperglycemia results in damages to tissue, which also causes dysfunctions of some organ systems, including enzyme or hormone secretions. Commonly, dysfunction or insufficiency of pancreatic exocrine is evaluated by increasing activity of serum pancreatic enzyme, such as amylase and lipase. Although incidence of pancreatitis was found in Indonesian T2D, the pathogenic mechanism still unclear. The aim of this study was to characterize the marker protein that indicated the correlation of pancreatic exocrine insufficiency with progression of T2D. Proteomic analysis using LC-MS/MS was used in identification and characterization of protein marker which indicates insufficiency pancreatic exocrine. First step, protein profile was analyzed by SDS-PAGE methods using serum sample of T2D compared with normal or healthy control, as negative control, and pancreatitis patients, as positive control. Protein with 18 kDa was found as a candidate protein marker which indicated the pancreatic exocrine insufficiency in T2D. The further identification of that protein using LC-MS/MS showed 4 peptide fragments. In silico analysis of the peptide fragment indicated the correlation of pancreatic exocrine insufficiency with progression of T2D was METTL10 - methyltransferase like protein-10.

  2. Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity

    PubMed Central

    Navina, Sarah; Acharya, Chathur; DeLany, James P.; Orlichenko, Lidiya S.; Baty, Catherine J.; Shiva, Sruti S.; Durgampudi, Chandra; Karlsson, Jenny M.; Lee, Kenneth; Bae, Kyongtae T.; Furlan, Alessandro; Behari, Jaideep; Liu, Shiguang; McHale, Teresa; Nichols, Larry; Papachristou, Georgios Ioannis; Yadav, Dhiraj; Singh, Vijay P.

    2012-01-01

    Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid–mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis. PMID:22049070

  3. Difference gel electrophoresis (DiGE) identifies differentially expressed proteins in endoscopically-collected pancreatic fluid

    PubMed Central

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

    2012-01-01

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

  4. Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal and Pancreatic Cancer Mice.

    PubMed

    Quirin, Kayla A; Kwon, Jason J; Alioufi, Arafat; Factora, Tricia; Temm, Constance J; Jacobsen, Max; Sandusky, George E; Shontz, Kim; Chicoine, Louis G; Clark, K Reed; Mendell, Joshua T; Korc, Murray; Kota, Janaiah

    2018-03-16

    Recombinant adeno-associated virus (rAAV)-mediated gene delivery shows promise to transduce the pancreas, but safety/efficacy in a neoplastic context is not well established. To identify an ideal AAV serotype, route, and vector dose and assess safety, we have investigated the use of three AAV serotypes (6, 8, and 9) expressing GFP in a self-complementary (sc) AAV vector under an EF1α promoter (scAAV.GFP) following systemic or retrograde pancreatic intraductal delivery. Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but gene expression did not exceed >45% with the highest dose, 5 × 10 12 viral genomes (vg). Intraductal delivery of 1 × 10 11 vg scAAV6.GFP transduced acini, ductal cells, and islet cells with >50%, ∼48%, and >80% efficiency, respectively, and >80% pancreatic transduction was achieved with 5 × 10 11 vg. In a Kras G12D -driven pancreatic cancer mouse model, intraductal delivery of scAAV6.GFP targeted acini, epithelial, and stromal cells and exhibited persistent gene expression 5 months post-delivery. In normal mice, intraductal delivery induced a transient increase in serum amylase/lipase that resolved within a day of infusion with no sustained pancreatic inflammation or fibrosis. Similarly, in PDAC mice, intraductal delivery did not increase pancreatic intraepithelial neoplasia progression/fibrosis. Our study demonstrates that scAAV6 targets the pancreas/neoplasm efficiently and safely via retrograde pancreatic intraductal delivery.

  5. The Role of Endocannabinoid Signaling in Cortical Inhibitory Neuron Dysfunction in Schizophrenia

    PubMed Central

    Volk, David W.; Lewis, David A.

    2015-01-01

    Cannabis use has been reported to increase the risk of developing schizophrenia and to worsen symptoms of the illness. Both of these outcomes might be attributable to the disruption by cannabis of the endogenous cannabinoid system's spatiotemporal regulation of the inhibitory circuitry in the prefrontal cortex that is essential for core cognitive processes, such as working memory, which are impaired in schizophrenia. In the healthy brain, the endocannabinoid 2-arachidonylglycerol (2-AG) is 1) synthesized by diacylglycerol lipase in pyramidal neurons; 2) travels retrogradely to nearby inhibitory axon terminals that express the primary cannabinoid receptor CB1R; 3) binds to CB1R which inhibits GABA release from the cholecystokinin-containing population of interneurons; and 4) is metabolized by either monoglyceride lipase, which is located in the inhibitory axon terminal, or by α-β-hydrolase domain 6, which is co-localized presynaptically with diacylglycerol lipase. Investigations of the endogenous cannabinoid system in the prefrontal cortex of subjects with schizophrenia have found evidence of higher metabolism of 2-AG, as well as both greater CB1R receptor binding and lower levels of CB1R mRNA and protein. Current views on the potential pathogenesis of these alterations, including disturbances in the development of the endogenous cannabinoid system, are discussed. In addition, how interactions between these alterations in the endocannabinoid system and those in other inhibitory neurons in the prefrontal cortex in subjects with schizophrenia might increase the liability to adverse outcomes with cannabis use is considered. PMID:26210060

  6. Canine Pancreas-Specific Lipase and C-reactive Protein in Dogs Treated With Anticonvulsants (Phenobarbital and Potassium Bromide).

    PubMed

    Albarracín, Viviana; Teles, Mariana; Meléndez-Lazo, Antonio; Rodón, Jaume; Pastor, Josep

    2015-06-01

    Animals treated with anticonvulsant drugs may have increased canine pancreas-specific lipase (cPLI) values. Inflammatory conditions and specifically acute pancreatitis are of major concern in these animals. Elevation in C-reactive protein is being associated with inflammatory status in dogs and it has been correlated with the clinical severity of pancreatitis. In the present study, we investigated if there is a correlation between the cPLI increase, changes in C-reactive protein and hepatic enzymes, as well as the incidence of severe acute pancreatitis (AP) in dogs with anticonvulsant treatment (phenobarbital, or potassium bromide or both). Increased values of pancreas-specific lipase were found in 6.8% of the animals in treatment with anticonvulsants, and this increase is correlated with the increase in triglycerides, alkaline phosphatase, and alanine aminotransferase but not with C-reactive protein levels, which suggests a possible induction or release phenomenon rather than a clear severe AP. C-reactive protein levels did not affect cPLI values on the population studied. Only 2 animals had clinical and analytical data suggestive of AP, indicating a low prevalence (0.6%). In conclusion, cPLI may be increased in a low percentage of animals with anticonvulsants treatment and its increase may not be associated with severe AP. It may be induced by the anticonvulsants drugs; however, further studies are advised to rule out other possible causes that increased cPLI. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Severe hypertriglyceridemia in a patient heterozygous for a lipoprotein lipase gene allele with two novel missense variants.

    PubMed

    Kassner, Ursula; Salewsky, Bastian; Wühle-Demuth, Marion; Szijarto, Istvan Andras; Grenkowitz, Thomas; Binner, Priska; März, Winfried; Steinhagen-Thiessen, Elisabeth; Demuth, Ilja

    2015-09-01

    Rare monogenic hyperchylomicronemia is caused by loss-of-function mutations in genes involved in the catabolism of triglyceride-rich lipoproteins, including the lipoprotein lipase gene, LPL. Clinical hallmarks of this condition are eruptive xanthomas, recurrent pancreatitis and abdominal pain. Patients with LPL deficiency and severe or recurrent pancreatitis are eligible for the first gene therapy treatment approved by the European Union. Therefore the precise molecular diagnosis of familial hyperchylomicronemia may affect treatment decisions. We present a 57-year-old male patient with excessive hypertriglyceridemia despite intensive lipid-lowering therapy. Abdominal sonography showed signs of chronic pancreatitis. Direct DNA sequencing and cloning revealed two novel missense variants, c.1302A>T and c.1306G>A, in exon 8 of the LPL gene coexisting on the same allele. The variants result in the amino-acid exchanges p.(Lys434Asn) and p.(Gly436Arg). They are located in the carboxy-terminal domain of lipoprotein lipase that interacts with the glycosylphosphatidylinositol-anchored HDL-binding protein (GPIHBP1) and are likely of functional relevance. No further relevant mutations were found by direct sequencing of the genes for APOA5, APOC2, LMF1 and GPIHBP1. We conclude that heterozygosity for damaging mutations of LPL may be sufficient to produce severe hypertriglyceridemia and that chylomicronemia may be transmitted in a dominant manner, at least in some families.

  8. Severe hypertriglyceridemia in a patient heterozygous for a lipoprotein lipase gene allele with two novel missense variants

    PubMed Central

    Kassner, Ursula; Salewsky, Bastian; Wühle-Demuth, Marion; Szijarto, Istvan Andras; Grenkowitz, Thomas; Binner, Priska; März, Winfried; Steinhagen-Thiessen, Elisabeth; Demuth, Ilja

    2015-01-01

    Rare monogenic hyperchylomicronemia is caused by loss-of-function mutations in genes involved in the catabolism of triglyceride-rich lipoproteins, including the lipoprotein lipase gene, LPL. Clinical hallmarks of this condition are eruptive xanthomas, recurrent pancreatitis and abdominal pain. Patients with LPL deficiency and severe or recurrent pancreatitis are eligible for the first gene therapy treatment approved by the European Union. Therefore the precise molecular diagnosis of familial hyperchylomicronemia may affect treatment decisions. We present a 57-year-old male patient with excessive hypertriglyceridemia despite intensive lipid-lowering therapy. Abdominal sonography showed signs of chronic pancreatitis. Direct DNA sequencing and cloning revealed two novel missense variants, c.1302A>T and c.1306G>A, in exon 8 of the LPL gene coexisting on the same allele. The variants result in the amino-acid exchanges p.(Lys434Asn) and p.(Gly436Arg). They are located in the carboxy-terminal domain of lipoprotein lipase that interacts with the glycosylphosphatidylinositol-anchored HDL-binding protein (GPIHBP1) and are likely of functional relevance. No further relevant mutations were found by direct sequencing of the genes for APOA5, APOC2, LMF1 and GPIHBP1. We conclude that heterozygosity for damaging mutations of LPL may be sufficient to produce severe hypertriglyceridemia and that chylomicronemia may be transmitted in a dominant manner, at least in some families. PMID:25585702

  9. [External pancreatic fistulas management].

    PubMed

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

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

  10. Lipolytic Potential of Aspergillus japonicus LAB01: Production, Partial Purification, and Characterisation of an Extracellular Lipase

    PubMed Central

    Souza, Lívia Tereza Andrade; Oliveira, Jamil S.; dos Santos, Vera L.; Regis, Wiliam C. B.; Santoro, Marcelo M.; Resende, Rodrigo R.

    2014-01-01

    Lipolytic potential of Aspergillus japonicus LAB01 was investigated by describing the catalytic properties and stability of a secreted extracellular lipase. Enzyme production was considered high under room temperature after 4 days using sunflower oil and a combination of casein with sodium nitrate. Lipase was partially purified by 3.9-fold, resulting in a 44.2% yield using ammonium sulphate precipitation (60%) quantified with Superose 12 HR gel filtration chromatography. The activity of the enzyme was maximised at pH 8.5, and the enzyme demonstrated stability under alkaline conditions. The optimum temperature was found to be 45°C, and the enzyme was stable for up to 100 minutes, with more than 80% of initial activity remaining after incubation at this temperature. Partially purified enzyme showed reasonable stability with triton X-100 and was activated in the presence of organic solvents (toluene, hexane, and methanol). Among the tested ions, only Cu2+, Ni2+, and Al3+ showed inhibitory effects. Substrate specificity of the lipase was higher for C14 among various p-nitrophenyl esters assayed. The KM and V max values of the purified enzyme for p-nitrophenyl palmitate were 0.13 mM and 12.58 umol/(L·min), respectively. These features render a novel biocatalyst for industrial applications. PMID:25530954

  11. Genetic Variants Associated with Gestational Hypertriglyceridemia and Pancreatitis

    PubMed Central

    Huang, Xie-Lin; Chen, Chao; Jin, Rong; Huang, Zhi-Ming; Zhou, Meng-Tao

    2015-01-01

    Severe hypertriglyceridemia is a well-known cause of pancreatitis. Usually, there is a moderate increase in plasma triglyceride level during pregnancy. Additionally, certain pre-existing genetic traits may render a pregnant woman susceptible to development of severe hypertriglyceridemia and pancreatitis, especially in the third trimester. To elucidate the underlying mechanism of gestational hypertriglyceridemic pancreatitis, we undertook DNA mutation analysis of the lipoprotein lipase (LPL), apolipoprotein C2 (APOC2), apolipoprotein A5 (APOA5), lipase maturation factor 1 (LMF1), and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) genes in five unrelated pregnant Chinese women with severe hypertriglyceridemia and pancreatitis. DNA sequencing showed that three out of five patients had the same homozygous variation, p.G185C, in APOA5 gene. One patient had a compound heterozygous mutation, p.A98T and p.L279V, in LPL gene. Another patient had a compound heterozygous mutation, p.A98T & p.C14F in LPL and GPIHBP1 gene, respectively. No mutations were seen in APOC2 or LMF1 genes. All patients were diagnosed with partial LPL deficiency in non-pregnant state. As revealed in our study, genetic variants appear to play an important role in the development of severe gestational hypertriglyceridemia, and, p.G185C mutation in APOA5 gene appears to be the most common variant implicated in the Chinese population. Antenatal screening for mutations in susceptible women, combined with subsequent interventions may be invaluable in the prevention of potentially life threatening gestational hypertriglyceridemia-induced pancreatitis. PMID:26079787

  12. Use of a fluorescent radiolabeled triacylglycerol as a substrate for lipoprotein lipase and hepatic triglyceride lipase

    SciTech Connect

    Dousset, N.; Negre, A.; Salvayre, R.

    1988-06-01

    A fluorescent radiolabeled triacylglycerol has been synthesized by using a fluorescent fatty acid (pyrene decanoic acid) and a radiolabeled oleic acid. This analog of the natural substrate, 1(3)pyrene decanoic-2,3 (1,2)-dioleoyl-sn-glycerol, has been tested as substrate for determining lipoprotein lipase and hepatic triacylglycerol lipase activities in post-heparin plasma. Optimal conditions for the determination of the two post-heparin plasma lipases were similar to those using radiolabeled triolein. Using this substrate, both post-heparin lipases exhibited their characteristic properties (pH optimum and effect of inhibitors) and attacked external ester bonds (1 or 3) containing pyrene decanoic and oleic acids at a similar rate.

  13. Investigation of procalcitonin, IL-6, oxidative stress index (OSI) plasma and tissue levels in experimental mild and severe pancreatitis in rats.

    PubMed

    Soyalp, M; Yalcin, M; Oter, V; Ozgonul, A

    2017-01-01

    This study was planned to evaluate blood and tissue levels of procalcitonin, IL-6 and Oxidative Stress Index (OSI), which have a role in the pathophysiology of inflammation, in rats with experimental mild and severe pancreatitis. Thirty male Wistar Albino rats were included in the study and the rats were equally divided into the three groups. After 1, 5 and 24 hours, blood was obtained from the tail of all rats and samples were taken from pancreas tissue after 24 hours. Amylase, lipase, AST, ALT, WBC, LDH, glucose, total bilirubin, direct bilirubin, GGT, ALP and TNF-α, Procalcitonin and IL-6 levels were evaluated from blood and tissue specimens. The mild pancreatitis group (group 1) and the severe pancreatitis group (group 3) were compared according to the OSI, Amylase, Lipase, Pct, IL-6, AST, ALT, Glucose, WBC, LDH and Tnf-α levels. In the severe pancreatitis group, a statistically significant increase was detected compared to the mild pancreatitis group (p < 0.05). There was no statistically significant difference in TOS, T.Bil, D.Bil, GGT and ALP values (p > 0.05). Statistically significant increase was observed in severe pancreatitis group according to OSI, Amylase, Lipase, Pct, IL-6, LDH, WBC and TNF-α levels samples obtained from pancreatic tissues, compared to mild pancreatitis group (p < 0.05). In conclusion, our study showed that OSI, TNF-α, IL-6 and procalcitonin levels increases proportionally with the severity of pancreatitis. This also suggests that OSI, TNF-α, IL-6 and procalcitonin are the guiding substances in acute pancreatitis, and that this damage increases as the duration and severity of the pathological process increase. However, this result must be confirmed with more detailed and broadly planned future studies (Fig. 3, Ref. 25).

  14. Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol

    SciTech Connect

    Kaphalia, Bhupendra S., E-mail: bkaphali@utmb.ed; Bhopale, Kamlesh K.; Kondraganti, Shakuntala

    2010-08-01

    Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH{sup -}) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH{sup -} and hepatic ADH-normal (ADH{sup +}) deer mice fed 1%, 2% or 3.5% ethanolmore » via Lieber-DeCarli liquid diet daily for 2 months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was {approx} 1.5-fold greater in ADH{sup -} vs. ADH{sup +} deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH{sup -} deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis.« less

  15. The second case of a young man with L-arginine-induced acute pancreatitis.

    PubMed

    Binet, Quentin; Dufour, Inès; Agneessens, Emmanuel; Debongnie, Jean-Claude; Aouattah, Tarik; Covas, Angélique; Coche, Jean-Charles; De Koninck, Xavier

    2018-04-21

    Dietary supplementation of arginine has been used by numerous world-class athletes and professional bodybuilders over the past 30 years. L-Arginine indeed enhances muscular power and general performance via maintaining ATP level. However, L-arginine is also known to induce acute pancreatitis in murine models. We report the case of young man presenting with upper abdominal pain and increased serum lipase levels. Contrast-enhanced computed tomography confirms a mild acute pancreatitis. Common etiologies have been ruled out and toxicological anamnestic screening reveals the intake of protein powder. This is, to the best of our knowledge, the second case in human of arginine-induced acute pancreatitis. This case report suggests that every patient presenting with acute pancreatitis without obvious etiology should be evaluated for the intake of toxics other than alcohol, including L-arginine.

  16. Acute pancreatitis with saw palmetto use: a case report.

    PubMed

    Bruminhent, Jackrapong; Carrera, Perliveh; Li, Zhongzhen; Amankona, Raymond; Roberts, Ingram M

    2011-08-25

    Saw palmetto is a phytotherapeutic agent commercially marketed for the treatment of benign prostatic hyperplasia. Evidence suggests that saw palmetto is a safe product, and mild gastrointestinal adverse effects have been reported with its use. We report a case of acute pancreatitis, possibly secondary to the use of saw palmetto. A 61-year-old Caucasian man with a history of benign prostatic hyperplasia and gastroesophageal reflux disease developed epigastric pain associated with nausea 36 hours prior to presentation. He denied drinking alcohol prior to the development of his symptoms. His home medications included saw palmetto, lansoprazole and multivitamins. Laboratory results revealed elevated lipase and amylase levels. An abdominal ultrasound demonstrated a nondilated common bile duct, without choledocholithiasis. Computed tomography of his abdomen showed the pancreatic tail with peripancreatic inflammatory changes, consistent with acute pancreatitis. Our patient's condition improved with intravenous fluids and pain management. On the fourth day of hospitalization his pancreatic enzymes were within normal limits: he was discharged home and advised to avoid taking saw palmetto. It is our opinion that a relationship between saw palmetto and the onset of acute pancreatitis is plausible, and prescribers and users of saw palmetto should be alert to the possibility of such adverse reactions.

  17. Acute pancreatitis with saw palmetto use: a case report

    PubMed Central

    2011-01-01

    Introduction Saw palmetto is a phytotherapeutic agent commercially marketed for the treatment of benign prostatic hyperplasia. Evidence suggests that saw palmetto is a safe product, and mild gastrointestinal adverse effects have been reported with its use. We report a case of acute pancreatitis, possibly secondary to the use of saw palmetto. Case presentation A 61-year-old Caucasian man with a history of benign prostatic hyperplasia and gastroesophageal reflux disease developed epigastric pain associated with nausea 36 hours prior to presentation. He denied drinking alcohol prior to the development of his symptoms. His home medications included saw palmetto, lansoprazole and multivitamins. Laboratory results revealed elevated lipase and amylase levels. An abdominal ultrasound demonstrated a nondilated common bile duct, without choledocholithiasis. Computed tomography of his abdomen showed the pancreatic tail with peripancreatic inflammatory changes, consistent with acute pancreatitis. Our patient's condition improved with intravenous fluids and pain management. On the fourth day of hospitalization his pancreatic enzymes were within normal limits: he was discharged home and advised to avoid taking saw palmetto. Conclusion It is our opinion that a relationship between saw palmetto and the onset of acute pancreatitis is plausible, and prescribers and users of saw palmetto should be alert to the possibility of such adverse reactions. PMID:21867545

  18. Structural characterization of MAPLE deposited lipase biofilm

    NASA Astrophysics Data System (ADS)

    Aronne, Antonio; Ausanio, Giovanni; Bloisi, Francesco; Calabria, Raffaela; Califano, Valeria; Fanelli, Esther; Massoli, Patrizio; Vicari, Luciano R. M.

    2014-11-01

    Lipases (triacylglycerol ester hydrolases) are enzymes used in several industrial applications. Enzymes immobilization can be used to address key issues limiting widespread application at industrial level. Immobilization efficiency is related to the ability to preserve the native conformation of the enzyme. MAPLE (Matrix Assisted Pulsed Laser Evaporation) technique, a laser deposition procedure for treating organic/polymeric/biomaterials, was applied for the deposition of lipase enzyme in an ice matrix, using near infrared laser radiation. Microscopy analysis showed that the deposition occurred in micrometric and submicrometric clusters with a wide size distribution. AFM imaging showed that inter-cluster regions are uniformly covered with smaller aggregates of nanometric size. Fourier transform infrared spectroscopy was used for both recognizing the deposited material and analyzing its secondary structure. Results showed that the protein underwent reversible self-association during the deposition process. Actually, preliminary tests of MAPLE deposited lipase used for soybean oil transesterification with isopropyl alcohol followed by gas chromatography-mass spectrometry gave results consistent with undamaged deposition of lipase.

  19. Biotechnological applications of halophilic lipases and thioesterases.

    PubMed

    Schreck, Steven D; Grunden, Amy M

    2014-02-01

    Lipases and esterases are enzymes which hydrolyze ester bonds between a fatty acid moiety and an esterified conjugate, such as a glycerol or phosphate. These enzymes have a wide spectrum of use in industrial applications where their high activity, broad substrate specificity, and stability under harsh conditions have made them integral in biofuel production, textile processing, waste treatment, and as detergent additives. To date, these industrial applications have mainly leveraged enzymes from mesophilic and thermophilic organisms. However, increasingly, attention has turned to halophilic enzymes as catalysts in environments where high salt stability is desired. This review provides a brief overview of lipases and esterases and examines specific structural motifs and evolutionary adaptations of halophilic lipases. Finally, we examine the state of research involving these enzymes and provide an in-depth look at an exciting algal-based biofuel production system. This system uses a recombinant halophilic lipase to increase oil production efficiency by cleaving algal fatty acids from the acyl carrier protein, which eliminates feedback inhibition of fatty acid synthesis.

  20. PANCREATITIS AND CARCINOMA OF THE PANCREAS—Some Aspects of the Pathologic Physiology

    PubMed Central

    Edmondson, Hugh A.

    1952-01-01

    The physiological phenomena accompanying pancreatic disease in adults are related to the local and generalized reaction of the body to the blockage and/or leakage of the three enzymes—amylase, lipase and trypsin. The measurements of amylase and lipase in the serum are the most reliable criteria in the diagnosis of acute disease. Related changes may include hypocalcemia, hypopotassemia, hyperlipemia, hyperglycemia and decreased renal function. In chronic pancreatitis, there is less fluctuation in the amounts of the enzymes in the blood. The presence of diabetes mellitus, demonstration of calculi by x-ray, and examination of the stools for excess fat and meat fibers are more important diagnostic guides. In cancer of the pancreas, function tests using secretin stimulation of the gland followed by an examination of the external secretion or determination of the serum amylase have been used with some success. PMID:12988052

  1. Pancreatitis and carcinoma of the pancreas; some aspects of the pathologic physiology.

    PubMed

    EDMONDSON, H A

    1952-09-01

    The physiological phenomena accompanying pancreatic disease in adults are related to the local and generalized reaction of the body to the blockage and/or leakage of the three enzymes-amylase, lipase and trypsin. The measurements of amylase and lipase in the serum are the most reliable criteria in the diagnosis of acute disease. Related changes may include hypocalcemia, hypopotassemia, hyperlipemia, hyperglycemia and decreased renal function. In chronic pancreatitis, there is less fluctuation in the amounts of the enzymes in the blood. The presence of diabetes mellitus, demonstration of calculi by x-ray, and examination of the stools for excess fat and meat fibers are more important diagnostic guides. In cancer of the pancreas, function tests using secretin stimulation of the gland followed by an examination of the external secretion or determination of the serum amylase have been used with some success.

  2. Acute pancreatitis: a multisystem disease.

    PubMed

    Agarwal, N; Pitchumoni, C S

    1993-06-01

    Proteolytic enzymes, lipase, kinins, and other active peptides liberated from the inflamed pancreas convert inflammation of the pancreas, a single-organ disease of the retroperitoneum, to a multisystem disease. Adult respiratory distress syndrome, in addition to being secondary to microvascular thrombosis, may be the result of active phospholipase A (lecithinase), which digests lecithin, a major component of surfactant. Myocardial depression and shock are suspected to be secondary to vasoactive peptides and a myocardial depressant factor. Coagulation abnormalities may range from scattered intravascular thrombosis to severe disseminated intravascular coagulation. Acute renal failure has been explained on the basis of hypovolemia and hypotension. The renin-angiotensin alterations in acute pancreatitis (AP) as mediators of renal failure need to be studied. Metabolic complications include hypocalcemia, hyperlipemia, hyperglycemia, hypoglycemia, and diabetic ketoacidosis, of which hypocalcemia has been long recognized as an indicator of poor prognosis. The pathogenesis of hypocalcemia is multifactorial and includes calcium-soap formation, hormonal imbalances (e.g., parathyroid hormone, calcitonin, glucagon), binding of calcium by free fatty acid-albumin complexes, and intracellular translocation of calcium. Subcutaneous fat necrosis, arthritis, and Purtscher's retinopathy are rare. The various prognostic criteria of AP and other associated laboratory abnormalities are manifestations of systemic effects. Early recognition and appropriated management of these complications have resulted in improved prognosis of severe AP.

  3. The cholesteryl octanoate breath test: a new procedure for detection of pancreatic insufficiency in the rat.

    PubMed

    Mundlos, S; Rhodes, J B; Hofmann, A F

    1987-09-01

    A breath test for the detection of pancreatic insufficiency was developed and tested in rats. The test features the hydrophobic molecule cholesteryl-1-14C-octanoate, which liberates 14C-octanoic acid when hydrolyzed by carboxyl ester lipase (cholesterol esterase). The 14C-octanoate is absorbed passively and rapidly metabolized to 14CO2, which is excreted in expired air. The compound was administered as an emulsion of cholesteryl octanoate, triglyceride, and lecithin to rats with mild pancreatic insufficiency induced by injecting the pancreatic duct with zein. The animals had exocrine pancreatic hypofunction based on the enzyme content of pancreas at autopsy. Amylase was reduced by 97.1 +/- 1.4%, whereas chymotrypsin was reduced by 73 +/- 14%. The p-aminobenzoic acid test was abnormal at 1 wk (21.68 +/- 8.4%), but become normal at 3 months (72.08 +/- 5.8%) after zein injection. Despite this, the animals gained weight and absorbed fat normally. The 14CO2 excretion rate in the 110-min interval after feeding was significantly reduced to 60% of sham-operated animals. Peak 14CO2 collections 20 min after feeding were reduced by 75 +/- 11%. 14CO2 output was completely normalized by administration of pancreatin prior to the test meal. The results suggest that a sensitive, noninvasive method for detecting deficiency of pancreatic carboxyl ester lipase (cholesterol esterase) secretion in the rat has been developed.

  4. Pancreatic necrosis in New World camelids: 11 cases (1990-1998).

    PubMed

    Pearson, E G; Snyder, S P

    2000-07-15

    To determine clinical, clinicopathologic, and postmortem abnormalities in New World camelids with pancreatic necrosis. Retrospective study. 10 llamas and 1 alpaca. Medical records of animals in which a diagnosis of pancreatic necrosis had been made on the basis of histologic examination of necropsy specimens or on the basis of clinical signs and results of clinicopathologic testing were reviewed. The initial owner complaint varied, and various other conditions were diagnosed. Clinical and clinicopathologic abnormalities were vague. Amylase activity was higher in abdominal fluid than in serum in 5 of 7 animals, and lipase activity was higher in abdominal fluid than in serum in all 7. Four animals survived, and 7 died or were euthanatized. Only 1 of the animals that died had marked inflammation of the pancreatic parenchyma. All 7 had necrosis and saponification of fat in and surrounding the pancreas. Results suggest that pancreatic necrosis may develop in New World camelids, but clinical signs are vague, and the condition may easily be confused with other diseases. The only laboratory test that appeared to be helpful in the antemortem diagnosis of pancreatic necrosis was comparison of amylase and lipase activities in abdominal fluid and serum.

  5. Pancreatitis-imaging approach

    PubMed Central

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

    2014-01-01

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

  6. The effect of sulindac, a non-steroidal anti-inflammatory drug, attenuates inflammation and fibrosis in a mouse model of chronic pancreatitis

    PubMed Central

    2012-01-01

    Background Chronic pancreatitis is characterized by progressive fibrosis, pain and loss of exocrine and endocrine functions. The long-standing chronic pancreatitis and its associated pancreatic fibrosis are the most common pathogenic events involved in human pancreatic carcinogenesis, but the therapeutic strategies to chronic pancreatitis and the chemoprevention of pancreatic carcinogenesis are very limited. Methods We investigated the effect of sulindac, a non-steroidal anti-inflammatory drug (NSAID), on inhibition of chronic pancreatitis in a caerulein induced chronic pancreatitis mouse model. Results Sulindac significantly reduced the severity of chronic pancreatitis including the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The protein expression of phosphorylation of MEK/ERK was inhibited in the chronic pancreatic tissues by sulindac treatment as measured by Western blot assay. The levels of inflammatory cytokines including TNF-α and MCP-1 were also significantly decreased with sulindac treatment, as well as the expression of TGF-β, PDGF-β, SHH and Gli in the chronic pancreatic tissue detected by qPCR assay and confirmed by western blot assay. The activation of pancreatic satellet cells was also inhibited by sulindac as measured by the activity of α-smooth muscle actin (α-SMA) in the pancreatic tissue of chronic pancreatitis. Conclusions Sulindac is a promising reagent for the treatment of chronic pancreatitis via inhibition of inflammatory cell infiltration and stromal fibrosis, the inhibitory effect of sulindac on chronic pancreatitis may through targeting the activation ERK/MAPK signaling pathway. PMID:22920325

  7. Pathogenic mechanisms of pancreatitis

    PubMed Central

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

    2017-01-01

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

  8. Efficient biocatalyst by encapsulating lipase into nanoporous gold

    PubMed Central

    2013-01-01

    Lipases are one of the most important biocatalysts for biotechnological applications. Immobilization is an efficient method to increase the stability and reusability of lipases. In this study, nanoporous gold (NPG), a new kind of nanoporous material with tunable porosity and excellent biocompatibility, was employed as an effective support for lipase immobilization. The pore size of NPG and adsorption time played key roles in the construction of lipase-NPG biocomposites. The morphology and composition of NPG before and after lipase loading are verified using a scanning electron microscope, equipped with an energy-dispersive X-ray spectrometer. The resulting lipase-NPG biocomposites exhibited excellent catalytic activity and remarkable reusability. The catalytic activity of the lipase-NPG biocomposite with a pore size of 35 nm had no decrease after ten recycles. Besides, the lipase-NPG biocomposite exhibited high catalytic activity in a broader pH range and higher temperature than that of free lipase. In addition, the leaching of lipase from NPG could be prevented by matching the protein’s diameter and pore size. Thus, the encapsulation of enzymes within NPG is quite useful for establishing new functions and will have wide applications for different chemical processes. PMID:23601503

  9. Unraveling Pancreatic Segmentation.

    PubMed

    Renard, Yohann; de Mestier, Louis; Perez, Manuela; Avisse, Claude; Lévy, Philippe; Kianmanesh, Reza

    2018-04-01

    Limited pancreatic resections are increasingly performed, but the rate of postoperative fistula is higher than after classical resections. Pancreatic segmentation, anatomically and radiologically identifiable, may theoretically help the surgeon removing selected anatomical portions with their own segmental pancreatic duct and thus might decrease the postoperative fistula rate. We aimed at systematically and comprehensively reviewing the previously proposed pancreatic segmentations and discuss their relevance and limitations. PubMed database was searched for articles investigating pancreatic segmentation, including human or animal anatomy, and cadaveric or surgical studies. Overall, 47/99 articles were selected and grouped into 4 main hypotheses of pancreatic segmentation methodology: anatomic, vascular, embryologic and lymphatic. The head, body and tail segments are gross description without distinct borders. The arterial territories defined vascular segments and isolate an isthmic paucivascular area. The embryological theory relied on the fusion plans of the embryological buds. The lymphatic drainage pathways defined the lymphatic segmentation. These theories had differences, but converged toward separating the head and body/tail parts, and the anterior from posterior and inferior parts of the pancreatic head. The rate of postoperative fistula was not decreased when surgical resection was performed following any of these segmentation theories; hence, none of them appeared relevant enough to guide pancreatic transections. Current pancreatic segmentation theories do not enable defining anatomical-surgical pancreatic segments. Other approaches should be explored, in particular focusing on pancreatic ducts, through pancreatic ducts reconstructions and embryologic 3D modelization.

  10. Genetic susceptibility factors for alcohol-induced chronic pancreatitis.

    PubMed

    Aghdassi, Ali A; Weiss, F Ulrich; Mayerle, Julia; Lerch, Markus M; Simon, Peter

    2015-07-01

    Chronic pancreatitis is a progressive inflammatory disease of the pancreas and frequently associated with immoderate alcohol consumption. Since only a small proportion of alcoholics eventually develop chronic pancreatitis genetic susceptibility factors have long been suspected to contribute to the pathogenesis of the disease. Smaller studies in ethnically defined populations have found that not only polymorphism in proteins involved in the metabolism of ethanol, such as Alcohol Dehydrogenase and Aldehyde Dehydrogenase, can confer a risk for developing chronic pancreatitis but also mutations that had previously been reported in association with idiopathic pancreatitis, such as SPINK1 mutations. In a much broader approach employing genome wide search strategies the NAPS study found that polymorphisms in the Trypsin locus (PRSS1 rs10273639), and the Claudin 2 locus (CLDN2-RIPPLY1-MORC4 locus rs7057398 and rs12688220) confer an increased risk of developing alcohol-induced pancreatitis. These results from North America have now been confirmed by a European consortium. In another genome wide approach polymorphisms in the genes encoding Fucosyltransferase 2 (FUT2) non-secretor status and blood group B were not only found in association with higher serum lipase levels in healthy volunteers but also to more than double the risk for developing alcohol-associated chronic pancreatitis. These novel genetic associations will allow to investigate the pathophysiological and biochemical basis of alcohol-induced chronic pancreatitis on a cellular level and in much more detail than previously possible. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  11. Vitamin K3 attenuates cerulein-induced acute pancreatitis through inhibition of the autophagic pathway.

    PubMed

    Chinzei, Ryo; Masuda, Atsuhiro; Nishiumi, Shin; Nishida, Masayuki; Onoyama, Mitsuko; Sanuki, Tsuyoshi; Fujita, Tsuyoshi; Moritoh, Satoshi; Itoh, Tomoo; Kutsumi, Hiromu; Mizuno, Shigeto; Azuma, Takeshi; Yoshida, Masaru

    2011-01-01

    The discovery of novel and effective treatment methods would be of great help to patients with acute pancreatitis. The aims of this study were to determine the inhibitory effects of vitamin K3 (VK3) against cerulein-induced acute pancreatitis in mice and to examine the mechanisms behind these effects. Acute pancreatitis in mice was induced by intraperitoneal injection of cerulein 6 times at hourly intervals. Vitamin K3 was administered once before the first injection of cerulein or twice before and after the first injection of cerulein. The degrees of inflammation and autophagy in the pancreatic tissue were estimated by histological examination, measurement of enzyme activity, confocal microscopy, and Western blotting. The inhibitory effects of VK3 against rapamycin-induced autophagy were also examined using HeLa cells stably expressing green fluorescent protein LC3. Cerulein-induced acute pancreatitis was markedly attenuated by the administration of VK3. In addition, VK3 led to the inhibition of cerulein-evoked autophagic changes and colocalization of autophagosomes and lysosomes in the pancreatic tissue. Vitamin K3 also reduced rapamycin-induced autophagy in HeLa/green fluorescent protein LC3 cells. Our data suggest that the administration of VK3 reduces pancreatic inflammation in acute pancreatitis through inhibition of the autophagic pathway. Vitamin K3 may be an effective therapeutic strategy against acute pancreatitis.

  12. Differential effect of combined lipase deficiency (cld/cld) on human hepatic lipase and lipoprotein lipase secretion.

    PubMed

    Boedeker, J C; Doolittle, M H; White, A L

    2001-11-01

    Combined lipase deficiency (cld) is a recessively inherited disorder in mice associated with a deficiency of LPL and hepatic lipase (HL) activity. LPL is synthesized in cld tissues but is retained in the endoplasmic reticulum (ER), whereas mouse HL (mHL) is secreted but inactive. In this study we investigated the effect of cld on the secretion of human HL (hHL) protein mass and activity. Differentiated liver cell lines were derived from cld mice and their normal heterozygous (het) littermates by transformation of hepatocytes with SV40 large T antigen. After transient transfection with lipase expression constructs, secretion of hLPL activity from cld cells was only 12% of that from het cells. In contrast, the rate of secretion of hHL activity and protein mass per unit of expressed hHL mRNA was identical for the two cell lines. An intermediate effect was observed for mHL, with a 46% reduction in secretion of activity from cld cells. The ER glucosidase inhibitor, castanospermine, decreased secretion of both hLPL and hHL from het cells by approximately 70%, but by only approximately 45% from cld cells. This is consistent with data suggesting that cld may result from a reduced concentration of the ER chaperone calnexin. In conclusion, our results demonstrate a differential effect of cld on hLPL, mHL, and hHL secretion, suggesting differential requirements for activation and exit of the enzymes from the ER.

  13. Engineering Lipases: walking the fine line between activity and stability

    NASA Astrophysics Data System (ADS)

    Dasetty, Siva; Blenner, Mark A.; Sarupria, Sapna

    2017-11-01

    Lipases are enzymes that hydrolyze lipids and have several industrial applications. There is a tremendous effort in engineering the activity, specificity and stability of lipases to render them functional in a variety of environmental conditions. In this review, we discuss the recent experimental and simulation studies focused on engineering lipases. Experimentally, mutagenesis studies have demonstrated that the activity, stability, and specificity of lipases can be modulated by mutations. It has been particularly challenging however, to elucidate the underlying mechanisms through which these mutations affect the lipase properties. We summarize results from experiments and molecular simulations highlighting the emerging picture to this end. We end the review with suggestions for future research which underscores the delicate balance of various facets in the lipase that affect their activity and stability necessitating the consideration of the enzyme as a network of interactions.

  14. Pancreatic Cancer-Derived Exosomes Cause Paraneoplastic β-cell Dysfunction.

    PubMed

    Javeed, Naureen; Sagar, Gunisha; Dutta, Shamit K; Smyrk, Thomas C; Lau, Julie S; Bhattacharya, Santanu; Truty, Mark; Petersen, Gloria M; Kaufman, Randal J; Chari, Suresh T; Mukhopadhyay, Debabrata

    2015-04-01

    Pancreatic cancer frequently causes diabetes. We recently proposed adrenomedullin as a candidate mediator of pancreatic β-cell dysfunction in pancreatic cancer. How pancreatic cancer-derived adrenomedullin reaches β cells remote from the cancer to induce β-cell dysfunction is unknown. We tested a novel hypothesis that pancreatic cancer sheds adrenomedullin-containing exosomes into circulation, which are transported to β cells and impair insulin secretion. We characterized exosomes from conditioned media of pancreatic cancer cell lines (n = 5) and portal/peripheral venous blood of patients with pancreatic cancer (n = 20). Western blot analysis showed the presence of adrenomedullin in pancreatic cancer-exosomes. We determined the effect of adrenomedullin-containing pancreatic cancer exosomes on insulin secretion from INS-1 β cells and human islets, and demonstrated the mechanism of exosome internalization into β cells. We studied the interaction between β-cell adrenomedullin receptors and adrenomedullin present in pancreatic cancer-exosomes. In addition, the effect of adrenomedullin on endoplasmic reticulum (ER) stress response genes and reactive oxygen/nitrogen species generation in β cells was shown. Exosomes were found to be the predominant extracellular vesicles secreted by pancreatic cancer into culture media and patient plasma. Pancreatic cancer-exosomes contained adrenomedullin and CA19-9, readily entered β cells through caveolin-mediated endocytosis or macropinocytosis, and inhibited insulin secretion. Adrenomedullin in pancreatic cancer exosomes interacted with its receptor on β cells. Adrenomedullin receptor blockade abrogated the inhibitory effect of exosomes on insulin secretion. β cells exposed to adrenomedullin or pancreatic cancer exosomes showed upregulation of ER stress genes and increased reactive oxygen/nitrogen species. Pancreatic cancer causes paraneoplastic β-cell dysfunction by shedding adrenomedullin(+)/CA19-9(+) exosomes into

  15. Anti-lipase and antioxidant properties of 30 medicinal plants used in Oaxaca, México.

    PubMed

    Villa-Ruano, Nemesio; Zurita-Vásquez, Guilibaldo G; Pacheco-Hernández, Yesenia; Betancourt-Jiménez, Martha G; Cruz-Durán, Ramiro; Duque-Bautista, Horacio

    2013-01-01

    We report the results of in vitro anti-lipase and antioxidant assays using crude ethanolic extracts from 30 plants grown in Oaxaca, México. Anti-lipase tests were performed by using porcine pancreatic lipase (PPL) [EC 3.1.1.3] from Affymetrix/USB. The extracts of Solanum erianthum, Salvia microphylla, Brungmansia suaveolens and Cuphea aequipetala showed up to 60% PPL inhibition. The effect of these extracts on the kinetic parameters of PPL (Km= 0.36 mM, and Vmax=0.085 mM min -1) revealed that the alcoholic preparations of S. erianthum and C. aequipetala engendered a non-competitive inhibition (Vmax=0.055 mM min -1; Vmax= 0.053 mM min -1), whereas those of S. microphylla and B. suaveolens produced a mixed inhibition (Km= 0.567 mM, Vmax=0.051 mM min _1; Km=0.643 mM, Vmax= 0.042 mM min ¹). In addition to these findings, seven extracts from different plants were able to inhibit PPL in the range of 30-50%. Antioxidant tests against 2,2-Diphenyl-1-picryl hydrazyl (DPPH) confirmed that Arctostaphylos pungens, Gnaphalium roseum, Crotalaria pumila, Cuphea aequipetala, Rhus chondroloma, and Satureja laevigata possess relevant antioxidant activity (IC(5)0=50-80 μg mL¹). The general composition of the most effective ethanolic extracts was obtained in order to confirm their known chemistry reported by previous works. Comprehensive chemical analysis of the ethanolic extracts and their poisoning effects suggests that S. microphylla, C. aequipetala and A. pungens could be considered as the best sources with both desired properties.

  16. Immobilised lipases in the cosmetics industry.

    PubMed

    Ansorge-Schumacher, Marion B; Thum, Oliver

    2013-08-07

    Commercial products for personal care, generally perceived as cosmetics, have an important impact on everyday life worldwide. Accordingly, the market for both consumer products and specialty chemicals comprising their ingredients is considerable. Lipases have started to play a minor role as active ingredients in so-called 'functional cosmetics' as well as a major role as catalysts for the industrial production of various specialty esters, aroma compounds and active agents. Interestingly, both applications almost always require preparation by appropriate immobilisation techniques. In addition, for catalytic use special reactor concepts often have to be employed due to the mostly limited stability of these preparations. Nevertheless, these processes show distinct advantages based on process simplification, product quality and environmental footprint and are therefore apt to more and more replace traditional chemical processes. Here, for the first time a review on the various aspects of using immobilised lipases in the cosmetics industry is given.

  17. Lipoprotein lipase: genetics, lipid uptake, and regulation.

    PubMed

    Merkel, Martin; Eckel, Robert H; Goldberg, Ira J

    2002-12-01

    Lipoprotein lipase (LPL) regulates the plasma levels of triglyceride and HDL. Three aspects are reviewed. 1) Clinical implications of human LPL gene variations: common mutations and their effects on plasma lipids and coronary heart disease are discussed. 2) LPL actions in the nervous system, liver, and heart: the discussion focuses on LPL and tissue lipid uptake. 3) LPL gene regulation: the LPL promoter and its regulatory elements are described.

  18. Biodiesel production by transesterification using immobilized lipase.

    PubMed

    Narwal, Sunil Kumar; Gupta, Reena

    2013-04-01

    Biodiesel can be produced by transesterification of vegetable or waste oil catalysed by lipases. Biodiesel is an alternative energy source to conventional fuel. It combines environmental friendliness with biodegradability, low toxicity and renewability. Biodiesel transesterification reactions can be broadly classified into two categories: chemical and enzymatic. The production of biodiesel using the enzymatic route eliminates the reactions catalysed under acid or alkali conditions by yielding product of very high purity. The modification of lipases can improve their stability, activity and tolerance to alcohol. The cost of lipases and the relatively slower reaction rate remain the major obstacles for enzymatic production of biodiesel. However, this problem can be solved by immobilizing the enzyme on a suitable matrix or support, which increases the chances of re-usability. The main factors affecting biodiesel production are composition of fatty acids, catalyst, solvents, molar ratio of alcohol and oil, temperature, water content, type of alcohol and reactor configuration. Optimization of these parameters is necessary to reduce the cost of biodiesel production.

  19. Characterization of Purified Staphylococcal Lipase1

    PubMed Central

    Vadehra, D. V.; Harmon, L. G.

    1967-01-01

    Purified staphylococcal lipase had an optimal pH of 8.3 for activity at 37 C, and an optimal temperature of 45 C at pH 8.0. During storage, the enzyme lost less than 10% of the activity over a period of 21 days at 4 and -23 C. The enzyme retained 93% of the activity when heated for 30 min at 50 C and was 95% destroyed in 30 min at 70 C. The purified lipase was capable of hydrolyzing a variety of natural fats and oils. However, the enzyme was three times more active on nonhydrogenated soybean oil than on hydrogenated soybean oil with an iodine value of <3.0. The enzyme was also capable of hydrolyzing fatty acids on the α, β, and α′ positions of a synthetic mixed triglyceride. In general, the presence of oxidizing agents increased the activity and the presence of reducing agents decreased the activity of the lipase enzyme. PMID:6035042

  20. Protective effect of Tribulus terrestris fruit extract on cerulein-induced acute pancreatitis in mice.

    PubMed

    Borran, Mina; Minaiyan, Mohsen; Zolfaghari, Behzad; Mahzouni, Parvin

    2017-01-01

    Antioxidant, anti-inflammatory, analgesic and antimicrobial activities of Tribulus terrestris ( T. terrestris ) could be helpful in the treatment of acute pancreatitis; thus, this study was designed to investigate the effects of T. terrestris on cerulein-induced acute pancreatitis in mice. Three doses (100, 200 and 400 mg/kg) of T. terrestris hydro-alcoholic extract were administered both orally (60 minutes before pancreatitis induction, p.o.) and intra-peritoneally (30 minutes before pancreatitis induction, i.p.) to different groups of mice (n=6). Pancreatitis was induced by five injections (i.p.) of cerulein 50μg/kg body weight with 1 hr intervals. Animals were euthanized 5 hr after the last injection of cerulein and tissue injures were assessed biochemically and pathologically. T. terrestris extract 200 and 400mg/kg (p.o.) and T. terrestris extract 400 mg/kg (i.p.) reduced pancreatic tissue myeloperoxidase (MPO) activity and serum amylase and lipase levels and alleviated histological parameters. These data suggest that T. terrestris hydro-alcoholic extract was effective in protecting against experimental acute pancreatitis and possibly the efficacy depends on dose and route of administration.

  1. Protective effect of Tribulus terrestris fruit extract on cerulein-induced acute pancreatitis in mice

    PubMed Central

    Borran, Mina; Minaiyan, Mohsen; Zolfaghari, Behzad; Mahzouni, Parvin

    2017-01-01

    Objective: Antioxidant, anti-inflammatory, analgesic and antimicrobial activities of Tribulus terrestris (T. terrestris) could be helpful in the treatment of acute pancreatitis; thus, this study was designed to investigate the effects of T. terrestris on cerulein-induced acute pancreatitis in mice. Materials and Methods: Three doses (100, 200 and 400 mg/kg) of T. terrestris hydro-alcoholic extract were administered both orally (60 minutes before pancreatitis induction, p.o.) and intra-peritoneally (30 minutes before pancreatitis induction, i.p.) to different groups of mice (n=6). Pancreatitis was induced by five injections (i.p.) of cerulein 50μg/kg body weight with 1 hr intervals. Animals were euthanized 5 hr after the last injection of cerulein and tissue injures were assessed biochemically and pathologically. Results: T. terrestris extract 200 and 400mg/kg (p.o.) and T. terrestris extract 400 mg/kg (i.p.) reduced pancreatic tissue myeloperoxidase (MPO) activity and serum amylase and lipase levels and alleviated histological parameters. Conclusion: These data suggest that T. terrestris hydro-alcoholic extract was effective in protecting against experimental acute pancreatitis and possibly the efficacy depends on dose and route of administration. PMID:28748172

  2. Acute Pancreatitis Complicated with Diabetic Ketoacidosis in a Young Adult without Hypertriglyceridemia: A Case Report.

    PubMed

    Kim, Jung Hyun; Oh, Myung Jin

    2016-11-25

    Systemic complications related to acute pancreatitis include acute respiratory distress syndrome, multiple organ dysfunction syndrome, disseminated intravascular coagulation, hypocalcemia, hyperglycemia, and insulin dependent diabetes or diabetic ketoacidosis. In practice, the development of diabetic ketoacidosis induced by acute pancreatitis is rare and generally associated with hypertriglyceridemia. However, herein we report a case of a 34-year-old female without hypertriglyceridemia, who was diagnosed with acute pancreatitis complicated with diabetic ketoacidosis. The patient was admitted with complaints of febrile sensation, back pain, and abdominal pain around the epigastric area. Levels of serum amylase and lipase were elevated to 663 U/L and 3,232 U/L. Contrast-enhanced abdominal CT showed pancreatic swelling, peri-pancreatic fat infiltration and fluid collection. The patient was initially diagnosed with simple acute pancreatitis. Though the symptoms were rapidly relieved after initiation of treatment, severe hyperglycemia (575 mg/dL), severe metabolic acidosis (pH 6.9), and ketonuria developed at four days after hospitalization. However, serum triglyceride levels remained within the normal range (134 mg/dL). Finally, the patient was diagnosed with acute pancreatitis complicated with diabetic ketoacidosis unrelated to hypertriglyceridemia. She recovered through insulin and fluid therapy, and receives insulin therapy at the outpatient clinic.

  3. Endocrine pancreatic function changes after acute pancreatitis.

    PubMed

    Wu, Deqing; Xu, Yaping; Zeng, Yue; Wang, Xingpeng

    2011-10-01

    This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP). Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated. Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P < 0.01). The islet β-cell function of patients was lower than that of controls (P < 0.01), whereas insulin resistance index was higher among patients (P < 0.01). Obesity, hyperlipidemia, and diabetes-related symptoms were found to be associated with endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time. Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

  4. Immobilization of a Commercial Lipase from Penicillium camembertii (Lipase G) by Different Strategies

    PubMed Central

    Mendes, Adriano A.; Freitas, Larissa; de Carvalho, Ana Karine F.; de Oliveira, Pedro C.; de Castro, Heizir F.

    2011-01-01

    The objective of this work was to select the most suitable procedure to immobilize lipase from Penicillium camembertii (Lipase G). Different techniques and supports were evaluated, including physical adsorption on hydrophobic supports octyl-agarose, poly(hydroxybutyrate) and Amberlite resin XAD-4; ionic adsorption on the anionic exchange resin MANAE-agarose and covalent attachment on glyoxyl-agarose, MANAE-agarose cross-linked with glutaraldehyde, MANAE-agarose-glutaraldehyde, and epoxy-silica-polyvinyl alcohol composite. Among the tested protocols, the highest hydrolytic activity (128.2 ± 8.10 IU·g−1 of support) was achieved when the lipase was immobilized on epoxy-SiO2-PVA using hexane as coupling medium. Lipase immobilized by ionic adsorption on MANAE-agarose also gave satisfactory result, attaining 55.6 ± 2.60 IU·g−1 of support. In this procedure, the maximum loading of immobilized enzyme was 9.3 mg·g−1 of gel, and the highest activity (68.8 ± 2.70 IU·g−1 of support) was obtained when 20 mg of protein·g−1 was offered. Immobilization carried out in aqueous medium by physical adsorption on hydrophobic supports and covalent attachment on MANAE-agarose-glutaraldehyde and glyoxyl-agarose was shown to be unfeasible for Lipase G. Thermal stability tests revealed that the immobilized derivative on epoxy-SiO2-PVA composite using hexane as coupling medium had a slight higher thermal stability than the free lipase. PMID:21811674

  5. Quetiapine-induced hypertriglyceridaemia causing acute pancreatitis.

    PubMed

    Franco, John Mark; Vallabhajosyula, Saraschandra; Griffin, Timothy John

    2015-05-14

    Second-generation antipsychotics have well-known metabolic side effects such as hyperlipidaemia and hyperglycaemia. A middle-aged man presented with epigastric and flank pain associated with nausea, and was noted to have elevated triglycerides (3590 mg/dL or 40.53 mmol/L), lipase and glucose. Haematological parameters revealed neutropenia with pancytopaenia. The patient was started on conservative management for acute pancreatitis, and on intravenous insulin and oral gemfibrozil for lowering of his triglycerides. He gradually improved and was transitioned to oral atorvastatin and fenofibrate. His triglycerides, glucose and leucocyte counts normalised at discharge and he was transitioned to ziprasidone. The combination of hypertriglyceridaemia, worsening hyperglycaemia and neutropenia made us suspect quetiapine as the causative agent. Medications cause only 0.1-7% of acute pancreatitis cases, with quetiapine implicated in only five-reported cases. Hypertriglyceridaemia (>600 mg/dL or 6.77 mmol/L) is frequently reported with quetiapine use, but severe hypertriglyceridaemia (>1000 mg/dL or 11.29 mmol/L) has been reported in <10 patients. 2015 BMJ Publishing Group Ltd.

  6. Quetiapine-induced hypertriglyceridaemia causing acute pancreatitis

    PubMed Central

    Franco, John Mark; Vallabhajosyula, Saraschandra; Griffin, Timothy John

    2015-01-01

    Second-generation antipsychotics have well-known metabolic side effects such as hyperlipidaemia and hyperglycaemia. A middle-aged man presented with epigastric and flank pain associated with nausea, and was noted to have elevated triglycerides (3590 mg/dL or 40.53 mmol/L), lipase and glucose. Haematological parameters revealed neutropenia with pancytopaenia. The patient was started on conservative management for acute pancreatitis, and on intravenous insulin and oral gemfibrozil for lowering of his triglycerides. He gradually improved and was transitioned to oral atorvastatin and fenofibrate. His triglycerides, glucose and leucocyte counts normalised at discharge and he was transitioned to ziprasidone. The combination of hypertriglyceridaemia, worsening hyperglycaemia and neutropenia made us suspect quetiapine as the causative agent. Medications cause only 0.1–7% of acute pancreatitis cases, with quetiapine implicated in only five-reported cases. Hypertriglyceridaemia (>600 mg/dL or 6.77 mmol/L) is frequently reported with quetiapine use, but severe hypertriglyceridaemia (>1000 mg/dL or 11.29 mmol/L) has been reported in <10 patients. PMID:25976202

  7. Evaluation of miR-216a and miR-217 as Potential Biomarkers of Acute Exocrine Pancreatic Toxicity in Rats.

    PubMed

    Wang, Jianying; Huang, Wenhu; Thibault, Stephane; Brown, Thomas P; Bobrowski, Walter; Gukasyan, Hovhannes J; Evering, Winston; Hu, Wenyue; John-Baptiste, Annette; Vitsky, Allison

    2017-02-01

    Detecting and monitoring exocrine pancreatic damage during nonclinical and clinical testing is challenging because classical biomarkers amylase and lipase have limited sensitivity and specificity. Novel biomarkers for drug-induced pancreatic injury are needed to improve safety assessment and reduce late-stage attrition rates. In a series of studies, miR-216a and miR-217 were evaluated as potential biomarkers of acute exocrine pancreatic toxicity in rats. Our results revealed that miR-216a and miR-217 were almost exclusively expressed in rat pancreas and that circulating miR-216a and miR-217 were significantly increased in rats following administration of established exocrine pancreatic toxicants caerulein (CL) and 1-cyano-2-hydroxy-3-butene (CHB) as well as in rats administered a proprietary molecule known to primarily affect the exocrine pancreas. Conversely, neither microRNA was increased in rats administered a proprietary molecule known to cause a lesion at the pancreatic endocrine-exocrine interface (EEI) or in rats administered an established renal toxicant. Compared with amylase and lipase, increases in miR-216a and miR-217 were of greater magnitude, persisted longer, and/or correlated better with microscopic findings within the exocrine pancreas. Our findings demonstrate that in rats, miR-216a and miR-217 are sensitive and specific biomarkers of acute exocrine pancreatic toxicity that may add value to the measurement of classical pancreatic biomarkers.

  8. Laparoscopic pancreatic cystogastrostomy.

    PubMed

    Obermeyer, Robert J; Fisher, William E; Salameh, Jihad R; Jeyapalan, Manjula; Sweeney, John F; Brunicardi, F Charles

    2003-08-01

    The purpose of the review was to evaluate the feasibility and outcome of laparoscopic pancreatic cystogastrostomy for operative drainage of symptomatic pancreatic pseudocysts. A retrospective review of all patients who underwent laparoscopic pancreatic cystogastrostomy between June 1997 and July 2001 was performed. Data regarding etiology of pancreatitis, size of pseudocyst, operative time, complications, and pseudocyst recurrence were collected and reported as median values with ranges. Laparoscopic pancreatic cystogastrostomy was attempted in 6 patients. Pseudocyst etiology included gallstone pancreatitis (3), alcohol-induced pancreatitis (2), and post-ERCP pancreatitis (1). The cystogastrostomy was successfully performed laparoscopically in 5 of 6 patients. However, the procedure was converted to open after creation of the cystgastrostomy in 1 of these patients. There were no complications in the cases completed laparoscopically and no deaths in the entire group. No pseudocyst recurrences were observed with a median followup of 44 months (range 4-59 months). Laparoscopic pancreatic cystgastrostomy is a feasible surgical treatment of pancreatic pseudocysts with a resultant low pseudocyst recurrence rate, length of stay, and low morbidity and mortality.

  9. A rare case of thrombotic microangiopathy triggered by acute pancreatitis.

    PubMed

    Singh, Kevin; Nadeem, Ahmed Jamal; Doratotaj, Behzad

    2017-05-15

    Thrombotic microangiopathy (TMA) occurring after acute pancreatitis is rarely described. Without prompt intervention, TMA can be, and often is, lethal, so prompt recognition is important. Here, we present a case of a 61-year-old woman with a history of alcohol misuse who presented with epigastric pain, nausea and vomiting after binge drinking. Elevated serum lipase and imaging were suggestive of acute-on-chronic pancreatitis. Although the patient's symptoms of acute pancreatitis subsided, her anaemia, thrombocytopenia and acute kidney injury worsened. A peripheral blood smear revealed schistocytes, prompting suspicion for TMA. Therapeutic plasma exchange (TPE) was promptly initiated and she completed 10 TPE sessions that improved her anaemia and serum creatinine and resolved the thrombocytopenia. Since TPE was effective and the ADAMTS13 assay revealed 55% activity in the absence of anti-ADAMTS13 IgG prior to initiation of therapy, a confident diagnosis of TMA caused by acute pancreatitis was made. There was no evidence of relapse 2 years later. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. CLINICAL AND THERAPEUTIC CORRELATIONS IN PATIENTS WITH SLIGHT ACUTE PANCREATITIS

    PubMed Central

    MUNHOZ-FILHO, Clewis Henri; BATIGÁLIA, Fernando; FUNES, Hamilton Luiz Xavier

    2015-01-01

    Background Acute pancreatitis is an inflammatory disease of the pancreas due to enzymatic autodigestion which can cause necrosis or multiple organ failure; its pathophysiology is not fully known yet. Aim To evaluate the correlation between clinical and therapeutic data in patients with mild acute pancreatitis. Methods A retrospective study in 55 medical records of patients admitted with acute mild pancreatitis was realized to analyze the association between age, leukocytosis, serum glutamic-oxaloacetic transaminase and lactate dehydrogenase, glucose, antibiotics, time admission and Ranson´s scores. Results There was a positive association between less intensive care (strict hydration, analgesia and monitoring of vital signs), early antibiotic therapy (monotherapy), early return to diet after 48 hours and laboratory control of the serum amylase and lipase (high in the first week and decreasing after 10 days, without any prognostic value). Conclusions Changes in the management of patients with mild acute pancreatitis, such as enteral nutrition, rational use of lower spectrum antibiotics and intensive care, have contributed significantly to the reduction of hospitalization time and mortality. PMID:25861064

  11. Toward the establishment of standardized in vitro tests for lipid-based formulations. 5. Lipolysis of representative formulations by gastric lipase.

    PubMed

    Bakala-N'Goma, Jean-Claude; Williams, Hywel D; Sassene, Philip J; Kleberg, Karen; Calderone, Marilyn; Jannin, Vincent; Igonin, Annabel; Partheil, Anette; Marchaud, Delphine; Jule, Eduardo; Vertommen, Jan; Maio, Mario; Blundell, Ross; Benameur, Hassan; Müllertz, Anette; Pouton, Colin W; Porter, Christopher J H; Carrière, Frédéric

    2015-04-01

    Lipid-based formulations (LBF) are substrates for digestive lipases and digestion can significantly alter their properties and potential to support drug absorption. LBFs have been widely examined for their behaviour in the presence of pancreatic enzymes. Here, the impact of gastric lipase on the digestion of representative formulations from the Lipid Formulation Classification System has been investigated. The pHstat technique was used to measure the lipolysis by recombinant dog gastric lipase (rDGL) of eight LBFs containing either medium (MC) or long (LC) chain triglycerides and a range of surfactants, at various pH values [1.5 to 7] representative of gastric and small intestine contents under both fasting and fed conditions. All LBFs were hydrolyzed by rDGL. The highest specific activities were measured at pH 4 with the type II and IIIA MC formulations that contained Tween®85 or Cremophor EL respectively. The maximum activity on LC formulations was recorded at pH 5 for the type IIIA-LC formulation. Direct measurement of LBF lipolysis using the pHstat, however, was limited by poor LC fatty acid ionization at low pH. Since gastric lipase initiates lipid digestion in the stomach, remains active in the intestine and acts on all representative LBFs, its implementation in future standardized in vitro assays may be beneficial. At this stage, however, routine use remains technically challenging.

  12. Protective effect of bacillopeptidase CFR5 from Bacillus subtilis CFR5 on cerulein-induced pancreatitis.

    PubMed

    Sharmila, G R; Venkateswaran, G

    2017-09-16

    Bacillopeptidase is a serine peptidase, known for its fibrinolytic activity. However, a very little information is known about its in vivo inflammatory and/or anti-inflammatory properties. Thus, to understand whether bacillopeptidase incorporation can regulate pancreatitis or not, the cerulein-induced pancreatitis model was used, and the role of bacillopeptidase on pancreatitis was studied. In this study, 46 kDa protein was purified from Bacillus subtilis and identified as bacillopeptidase CFR5 (BPC) through MS/MS analysis. The nutritional prophylactic group was orally fed with two doses of BPC (100 μg/Kg/BW of rat) 6 h before cerulein administration and analyzed for its effect on intestine and pancreas inflammation, cytokines, and pancreatitis marker gene expression. BPC administration significantly reduced the severity of pancreatitis by decreasing serum amylase, lipase, pancreatic edema and myeloperoxidase activity. The pretreatment with BPC suppressed the pancreatic pro-inflammatory and inflammatory cytokines production including IL-6, IL-1β, TNF-α, IL-2, IL-4, IL-5, IL-10, and IL-13 in both pancreas and serum samples. Moreover, BPC supplementation restored pancreatitis mediated disruption of intestinal barrier integrity by upregulating tight junction proteins (ZO-1, occludin), antimicrobial peptides (DEFB1, CRAMP), MUC-2, TFF3 expression and by enhancing SCFA's production. Pretreatment with BPC suppressed the intestinal inflammation with reduced cytokines production in the colon and ileal region of cerulein-induced pancreatitis. Thus, BPC based pretreatment protocol is a novel intervention to prevent acute pancreatitis. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. New lipase assay using Pomegranate oil coating in microtiter plates.

    PubMed

    Ülker, Serdar; Placidi, Camille; Point, Vanessa; Gadenne, Benoît; Serveau-Avesque, Carole; Canaan, Stéphane; Carrière, Frédéric; Cavalier, Jean-François

    2016-01-01

    Lipases play various roles in fat digestion, lipoprotein metabolism, and in the mobilization of fat stored in lipid bodies in animals, plants and microorganisms. In association with these physiological functions, there is an important field of research for discovering lipase inhibitors and developing new treatments of diseases such as obesity, atherosclerosis, diabetes and tuberculosis. In this context, the development of convenient, specific and sensitive analytical methods for the detection and assay of lipases and/or lipase inhibitors is of major importance. It is shown here that purified triacylglycerols (TAGs) from Punica granatum (Pomegranate) seed oil coated on microtiter plates can be used for the continuous assay of lipase activity by recording the variations with time of the UV absorption spectra at 275 nm. UV absorption is due the release of punicic acid (9Z,11E,13Z-octadeca-9,11,13-trienoic acid), a conjugated triene contained in Pomegranate oil. This new microtiter plate assay allows to accurately measure the activity of a wider range of lipases compared to the similar assay previously developed with Tung oil containing α-eleostearic acid (9Z,11E,13E-octadeca-9,11,13-trienoic acid), including the LipY lipase from Mycobacterium tuberculosis. Although punicic acid is a diastereoisomer of α-eleostearic acid, the Δ(13)cis double bound found in punicic acid gives a different structure to the acyl chain that probably favours the interaction of Pomegranate TAGs with the lipase active site. The microplate lipase assay using Pomegranate TAGs shows high sensitivity, reproducibility and remarkable relevance for the high-speed screening of lipases and/or lipase inhibitors directly from raw culture media without any purification step. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  14. Pancreatic and Pancreatic-Like Microbial Proteases Accelerate Gut Maturation in Neonatal Rats

    PubMed Central

    Prykhodko, Olena; Pierzynowski, Stefan G.; Nikpey, Elham; Arevalo Sureda, Ester; Fedkiv, Olexandr; Weström, Björn R.

    2015-01-01

    Objectives Postnatal gut maturation in neonatal mammals, either at natural weaning or after precocious inducement, is coinciding with enhanced enzymes production by exocrine pancreas. Since the involvement of enzymes in gut functional maturation was overlooked, the present study aimed to investigate the role of enzymes in gut functional maturation using neonatal rats. Methods Suckling rats (Rattus norvegicus) were instagastrically gavaged with porcine pancreatic enzymes (Creon), microbial-derived amylase, protease, lipase and mixture thereof, while controls received α-lactalbumin or water once per day during 14–16 d of age. At 17 d of age the animals were euthanized and visceral organs were dissected, weighed and analyzed for structural and functional properties. For some of the rats, gavage with the macromolecular markers such as bovine serum albumin and bovine IgG was performed 3 hours prior to blood collection to assess the intestinal permeability. Results Gavage with the pancreatic or pancreatic-like enzymes resulted in stimulated gut growth, increased gastric acid secretion and switched intestinal disaccharidases, with decreased lactase and increased maltase and sucrase activities. The fetal-type vacuolated enterocytes were replaced by the adult-type in the distal intestine, and macromolecular transfer to the blood was declined. Enzyme exposure also promoted pancreas growth with increased amylase and trypsin production. These effects were confined to the proteases in a dose-dependent manner. Conclusion Feeding exogenous enzymes, containing proteases, induced precocious gut maturation in suckling rats. This suggests that luminal exposure to proteases by oral loading or, possibly, via enhanced pancreatic secretion involves in the gut maturation of young mammals. PMID:25658606

  15. Pancreatic and pancreatic-like microbial proteases accelerate gut maturation in neonatal rats.

    PubMed

    Prykhodko, Olena; Pierzynowski, Stefan G; Nikpey, Elham; Arevalo Sureda, Ester; Fedkiv, Olexandr; Weström, Björn R

    2015-01-01

    Postnatal gut maturation in neonatal mammals, either at natural weaning or after precocious inducement, is coinciding with enhanced enzymes production by exocrine pancreas. Since the involvement of enzymes in gut functional maturation was overlooked, the present study aimed to investigate the role of enzymes in gut functional maturation using neonatal rats. Suckling rats (Rattus norvegicus) were instagastrically gavaged with porcine pancreatic enzymes (Creon), microbial-derived amylase, protease, lipase and mixture thereof, while controls received α-lactalbumin or water once per day during 14-16 d of age. At 17 d of age the animals were euthanized and visceral organs were dissected, weighed and analyzed for structural and functional properties. For some of the rats, gavage with the macromolecular markers such as bovine serum albumin and bovine IgG was performed 3 hours prior to blood collection to assess the intestinal permeability. Gavage with the pancreatic or pancreatic-like enzymes resulted in stimulated gut growth, increased gastric acid secretion and switched intestinal disaccharidases, with decreased lactase and increased maltase and sucrase activities. The fetal-type vacuolated enterocytes were replaced by the adult-type in the distal intestine, and macromolecular transfer to the blood was declined. Enzyme exposure also promoted pancreas growth with increased amylase and trypsin production. These effects were confined to the proteases in a dose-dependent manner. Feeding exogenous enzymes, containing proteases, induced precocious gut maturation in suckling rats. This suggests that luminal exposure to proteases by oral loading or, possibly, via enhanced pancreatic secretion involves in the gut maturation of young mammals.

  16. Neoadjuvant Chemotherapy Followed by Radiation Therapy and Gemcitabine/Sorafenib/Vorinostat in Pancreatic Cancer

    ClinicalTrials.gov

    2017-11-29

    Pancreatic Adenocarcinoma; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Recurrent Pancreatic Carcinoma

  17. Effects of thalidomide in experimental models of post-endoscopic retrograde cholangiopancreatography pancreatitis.

    PubMed

    Xiong, Guang-Su; Wu, Shu-Ming; Wang, Zhen-Hua; Mo, Jian-Zhong; Xiao, Shu-Dong

    2007-03-01

    Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the pathogenesis of acute pancreatitis and related systemic complications. The authors hypothesized that it may also play an important role in the development of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). The aim of the study was to evaluate the effectiveness of thalidomide, an immunomodulator that exerts an inhibitory action on TNF-alpha by enhancing mRNA degradation, in reducing post-ERCP pancreatitis in a rat model. A total of 200 mg/kg thalidomide was given intragastric once a day (total 8 days) before the experimental models of post-ERCP pancreatitis were established. After 24 h, histology and edema of pancreas, serum amylase, and TNF-alpha mRNA in the pancreatic tissue were evaluated. Intraductal contrast infusion caused increases in serum amylase, edema, histological grade, and TNF-alpha mRNA of pancreas. The prophylactic use of thalidomide significantly reduced serum amylase, pancreatic edema and the histologic grade of pancreatitis accompanied by a decrease in mRNA expression of TNF-alpha in the pancreatic tissue. Prophylactic intragastric administration of thalidomide provides a protective effect in post-ERCP pancreatitis. The mechanism of the protective effects of thalidomide seems to be the reduction of expression of TNF-alpha mRNA in pancreatic tissue.

  18. Long-term ingestion of cassava (tapioca) does not produce diabetes or pancreatitis in the rat model.

    PubMed

    Mathangi, D C; Deepa, R; Mohan, V; Govindarajan, M; Namasivayam, A

    2000-06-01

    Cassava (tapioca, manihot) is consumed as a staple food in some developing countries. The intake of cassava has been linked to several diseases including fibrocalculous pancreatic diabetes (tropical calcific pancreatitis). There are few long-term studies on the effect of cassava ingestion on the pancreas in animal models. This article reports on the long-term (up to 1 yr) effects of cassava in the rat model. We found that cassava did not produce diabetes in the rat even after a year of cassava feeding. There were transient changes in serum insulin and lipase levels, but the significance of these findings are not clear. There was no histopathological evidence of either acute or chronic pancreatitis, but there were changes of toxic hepatitis in the liver. In conclusion, chronic cassava ingestion up to a year does not lead to either diabetes or chronic pancreatitis in the rat model.

  19. Pancreatic stone protein (lithostathine), a physiologically relevant pancreatic calcium carbonate crystal inhibitor?

    PubMed

    Bimmler, D; Graf, R; Scheele, G A; Frick, T W

    1997-01-31

    Apart from digestive enzymes, pancreatic juice contains several proteins that are not directly involved in digestion. One of these, lithostathine, has been reported to exhibit calcite crystal inhibitor activity in vitro. As pancreatic juice is supersaturated with respect to calcium carbonate, it was hypothesized that lithostathine stabilizes pancreatic juice. Lithostathine is cleaved by trace amounts of trypsin, resulting in a C-terminal polypeptide and an N-terminal undecapeptide, which has been identified as the active site of lithostathine regarding crystal inhibition. We produced rat lithostathine in a baculovirus expression system. In order to test its functional activity, the protein was purified using a nondenaturing multi-step procedure. In the low micromolar range, recombinant rat lithostathine in vitro exhibited calcite crystal inhibitor activity, confirming earlier reports. Limited tryptic proteolysis of recombinant lithostathine was performed, and the two cleavage products were separated; the C-terminal polypeptide was precipitated by centrifugation, and the N-terminal undecapeptide was purified by high performance liquid chromatography. Only the C-terminal peptide displayed measurable calcite crystal inhibitory activity. Furthermore, synthetic undecapeptides with identical sequence to the N-terminal undecapeptides of rat or human lithostathine were inactive. However, when tested in the same in vitro assays, other pancreatic or extra-pancreatic proteins show inhibitory activity in the same concentration range as lithostathine, and inorganic phosphate is active as well. Based on these findings it seems unlikely that lithostathine is a physiologically relevant calcite crystal inhibitor. The name "lithostathine" is therefore inappropriate, and the protein's key function remains to be elucidated.

  20. Screening for Pancreatic Cancer

    PubMed Central

    Brand, Randall E.

    2007-01-01

    Despite improvements in the clinical and surgical management of pancreatic cancer, limited strides have been made in the early detection of this highly lethal malignancy. The majority of localized pancreatic tumors are asymptomatic, and the recognized presenting symptoms of pancreatic adenocarcinoma are often vague and heterogeneous in nature. These factors, coupled with the lack of a sensitive and noninvasive screening method, have made population-based screening for pancreatic cancer impossible. Nevertheless, at least two large institutions have performed multimodality-screening protocols for individuals with high risk of pancreatic cancer based on genetic predisposition and strong family history. Abnormalities noted during these screening protocols prompted further investigation or surgery that resulted in the discovery of benign, potentially malignant, and malignant pancreatic lesions. In addition to ductal epithelial pancreatic intraepithelial neoplasia, greater sensitivity has recently been achieved in the identification and characterization of precancerous mucinous pancreatic tumors. Advancements in proteomics and DNA microarray technology may confirm serum-based biomarkers that could be incorporated into future screening algorithms for pancreatic cancer. PMID:21960811

  1. Strain improvement of Aspergillus niger for enhanced lipase production.

    PubMed

    Sandana Mala, John Geraldine; Kamini, Numbi R.; Puvanakrishnan, Rengarajulu

    2001-08-01

    The enhancement of lipase production from Aspergillus niger was attempted by ultraviolet (UV) and nitrous acid mutagenesis, and the mutants were selected on media containing bile salts. Nitrous acid mutants exhibited increased efficiency for lipase production when compared with UV mutants in submerged fermentation. The hyperproducing UV and nitrous acid mutants were further subjected to a second step of mutagenesis to devise an economical and ecofriendly technique for lipase production by the effective use of hydrocarbons. One percent kerosene was found to be optimal for lipase production, and one of the mutant strains NAII exhibited 2.53 times more increased lipase activity than the parental strain did. This investigation indicates a possible role for the A. niger mutant strains in the biodegradation of oil-polluted environments for the development of ecofriendly technologies.

  2. Effect of bombesin on serum immunoreactive trypsin in healthy subjects and in patients with chronic pancreatitis.

    PubMed

    Labò, G; Vezzadini, P; Gullo, L; Sternini, C; Bonora, G

    1983-08-01

    We studied the effect of bombesin (9 ng/kg X min for 30 min by intravenous infusion) on serum immunoreactive trypsin in healthy subjects and in chronic pancreatitis patients. Bombesin administration caused a marked and significant increase of serum immunoreactive trypsin concentration in healthy subjects. The increase occurred in the first 15 min after the beginning of bombesin infusion and persisted for the duration of the study (2 h). In patients with chronic pancreatitis, the increase was much less pronounced. In these patients, the integrated immunoreactive trypsin response to bombesin was significantly correlated with bicarbonate, lipase, and chymotrypsin outputs into the duodenum. The response of serum immunoreactive trypsin to bombesin stimulation seems to vary according to the degree of pancreatic exocrine dysfunction and to reflect the functional capacity of acinar cell mass.

  3. Protection Provided by a Gabexate Mesylate Thermo-Sensitive In Situ Gel for Rats with Grade III Pancreatic Trauma.

    PubMed

    Gao, Hanjing; Song, Qing; Lv, Faqin; Wang, Shan; Wang, Yiru; Li, Xiaoyan; Luo, Yukun; Mei, Xingguo; Tang, Jie

    2017-01-15

    This study investigated the protection provided by gabexate mesylate thermo-sensitive in-situ gel (GMTI) against grade III pancreatic trauma in rats. A grade III pancreatic trauma model with main pancreatic duct dividing was established, and the pancreas anatomical diagram, ascites, and serum biochemical indices, including amylase, lipase, C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), were examined. The pancreas was sliced and stained with hematoxylin eosin and subjected to terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Ascites, serum amylase, lipase, CRP, IL-6, and TNF-α levels were significantly increased in the pancreas trauma (PT) groups with prolonged trauma time and were significantly decreased after GMTI treatment. The morphological structure of the pancreas was loose, the acinus was significantly damaged, the nuclei were irregular and hyperchromatic, and there was inflammatory cell invasion in the PT group compared to the control. After GMTI treatment, the morphological structure of the pancreas was restored, and the damaged acinus and inflammatory cell invasion were decreased compared to the PT group. Moreover, the cell apoptosis index was significantly increased in the PT group and restored to the same levels as the control group after GMTI treatment. GMTI, a novel formulation and drug delivery method, exhibited specific effective protection against PT with acute pancreatitis therapy and has potential value as a minimally invasive adjuvant therapy for PT with acute pancreatitis.

  4. Protection Provided by a Gabexate Mesylate Thermo-Sensitive In Situ Gel for Rats with Grade III Pancreatic Trauma

    PubMed Central

    Gao, Hanjing; Song, Qing; Lv, Faqin; Wang, Shan; Wang, Yiru; Li, Xiaoyan; Luo, Yukun; Mei, Xingguo; Tang, Jie

    2017-01-01

    Background/Aims This study investigated the protection provided by gabexate mesylate thermo-sensitive in-situ gel (GMTI) against grade III pancreatic trauma in rats. Methods A grade III pancreatic trauma model with main pancreatic duct dividing was established, and the pancreas anatomical diagram, ascites, and serum biochemical indices, including amylase, lipase, C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), were examined. The pancreas was sliced and stained with hematoxylin eosin and subjected to terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Results Ascites, serum amylase, lipase, CRP, IL-6, and TNF-α levels were significantly increased in the pancreas trauma (PT) groups with prolonged trauma time and were significantly decreased after GMTI treatment. The morphological structure of the pancreas was loose, the acinus was significantly damaged, the nuclei were irregular and hyperchromatic, and there was inflammatory cell invasion in the PT group compared to the control. After GMTI treatment, the morphological structure of the pancreas was restored, and the damaged acinus and inflammatory cell invasion were decreased compared to the PT group. Moreover, the cell apoptosis index was significantly increased in the PT group and restored to the same levels as the control group after GMTI treatment. Conclusions GMTI, a novel formulation and drug delivery method, exhibited specific effective protection against PT with acute pancreatitis therapy and has potential value as a minimally invasive adjuvant therapy for PT with acute pancreatitis. PMID:27646597

  5. Mechanism of acetaldehyde-induced deactivation of microbial lipases

    PubMed Central

    2011-01-01

    Background Microbial lipases represent the most important class of biocatalysts used for a wealth of applications in organic synthesis. An often applied reaction is the lipase-catalyzed transesterification of vinyl esters and alcohols resulting in the formation of acetaldehyde which is known to deactivate microbial lipases, presumably by structural changes caused by initial Schiff-base formation at solvent accessible lysine residues. Previous studies showed that several lipases were sensitive toward acetaldehyde deactivation whereas others were insensitive; however, a general explanation of the acetaldehyde-induced inactivation mechanism is missing. Results Based on five microbial lipases from Candida rugosa, Rhizopus oryzae, Pseudomonas fluorescens and Bacillus subtilis we demonstrate that the protonation state of lysine ε-amino groups is decisive for their sensitivity toward acetaldehyde. Analysis of the diverse modification products of Bacillus subtilis lipases in the presence of acetaldehyde revealed several stable products such as α,β-unsaturated polyenals, which result from base and/or amino acid catalyzed aldol condensation of acetaldehyde. Our studies indicate that these products induce the formation of stable Michael-adducts at solvent-accessible amino acids and thus lead to enzyme deactivation. Further, our results indicate Schiff-base formation with acetaldehyde to be involved in crosslinking of lipase molecules. Conclusions Differences in stability observed with various commercially available microbial lipases most probably result from different purification procedures carried out by the respective manufacturers. We observed that the pH of the buffer used prior to lyophilization of the enzyme sample is of utmost importance. The mechanism of acetaldehyde-induced deactivation of microbial lipases involves the generation of α,β-unsaturated polyenals from acetaldehyde which subsequently form stable Michael-adducts with the enzymes. Lyophilization of

  6. Substrate specificity and kinetic properties of enzymes belonging to the hormone-sensitive lipase family: comparison with non-lipolytic and lipolytic carboxylesterases.

    PubMed

    Chahinian, Henri; Ali, Yassine Ben; Abousalham, Abdelkarim; Petry, Stefan; Mandrich, Luigi; Manco, Guiseppe; Canaan, Stephane; Sarda, Louis

    2005-12-30

    We have studied the kinetics of hydrolysis of triacylglycerols, vinyl esters and p-nitrophenyl butyrate by four carboxylesterases of the HSL family, namely recombinant human hormone-sensitive lipase (HSL), EST2 from Alicyclobacillus acidocaldarius, AFEST from Archeoglobus fulgidus, and protein RV1399C from Mycobacterium tuberculosis. The kinetic properties of enzymes of the HSL family have been compared to those of a series of lipolytic and non-lipolytic carboxylesterases including human pancreatic lipase, guinea pig pancreatic lipase related protein 2, lipases from Mucor miehei and Thermomyces lanuginosus, cutinase from Fusarium solani, LipA from Bacillus subtilis, porcine liver esterase and Esterase A from Aspergilus niger. Results indicate that human HSL, together with other lipolytic carboxylesterases, are active on short chain esters and hydrolyze water insoluble trioctanoin, vinyl laurate and olive oil, whereas the action of EST2, AFEST, protein RV1399C and non-lipolytic carboxylesterases is restricted to solutions of short chain substrates. Lipolytic and non-lipolytic carboxylesterases can be differentiated by their respective value of K(0.5) (apparent K(m)) for the hydrolysis of short chain esters. Among lipolytic enzymes, those possessing a lid domain display higher activity on tributyrin, trioctanoin and olive oil suggesting, then, that the lid structure contributes to enzyme binding to triacylglycerols. Progress reaction curves of the hydrolysis of p-nitrophenyl butyrate by lipolytic carboxylesterases with lid domain show a latency phase which is not observed with human HSL, non-lipolytic carboxylesterases, and lipolytic enzymes devoid of a lid structure as cutinase.

  7. Harmful effect of detergents on lipase.

    PubMed

    Fatima, Sadaf; Ajmal, Rehan; Badr, Gamal; Khan, Rizwan H

    2014-11-01

    In order to study effects of detergents at molecular level, we have done activity measurements of wheat germ lipase in increasing concentration of some commercial detergents. Conformational changes in protein structure using circular dichroism and fluorescence spectroscopy were studied in increasing concentration of sodium dodecyl sulfate. Our study proves that detergents may lead to loss of enzymatic activity and structure of plant enzymes. Since detergents are common source of pollution in water bodies and the water from these resources can be used in fields, our study may prove helpful in creating awareness about harmful action of detergents.

  8. Screening and identification of Lipase Producing Bacterium

    NASA Astrophysics Data System (ADS)

    Zheng, Chaocheng

    2018-01-01

    55 samples from different regions were selected and screened by Rhodamine B flat transparent circle method to observe lipase producing effect, among which, LHY-1, identified as Serratia sp. has the characteristics of fast growth, high enzyme production and stable ability. The colony of this strain is white, the edge is smooth and tidy, the surface is moist, the cell is straight, rod-shaped, gram negative, 0.1-0.2 μm in diameter and, length 0.3-0.5 μm in length.

  9. 21 CFR 184.1420 - Lipase enzyme preparation derived from Rhizopus niveus.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Lipase enzyme preparation derived from Rhizopus... GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS § 184.1420 Lipase enzyme preparation derived from Rhizopus niveus. (a) Lipase enzyme preparation contains lipase enzyme (CAS Reg. No...

  10. 21 CFR 184.1420 - Lipase enzyme preparation derived from Rhizopus niveus.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Lipase enzyme preparation derived from Rhizopus... GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS § 184.1420 Lipase enzyme preparation derived from Rhizopus niveus. (a) Lipase enzyme preparation contains lipase enzyme (CAS Reg. No...

  11. 21 CFR 184.1420 - Lipase enzyme preparation derived from Rhizopus niveus.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Lipase enzyme preparation derived from Rhizopus... GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS § 184.1420 Lipase enzyme preparation derived from Rhizopus niveus. (a) Lipase enzyme preparation contains lipase enzyme (CAS Reg. No...

  12. 21 CFR 184.1420 - Lipase enzyme preparation derived from Rhizopus niveus.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Lipase enzyme preparation derived from Rhizopus... GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS § 184.1420 Lipase enzyme preparation derived from Rhizopus niveus. (a) Lipase enzyme preparation contains lipase enzyme (CAS Reg. No...

  13. 21 CFR 184.1420 - Lipase enzyme preparation derived from Rhizopus niveus.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Lipase enzyme preparation derived from Rhizopus... Specific Substances Affirmed as GRAS § 184.1420 Lipase enzyme preparation derived from Rhizopus niveus. (a) Lipase enzyme preparation contains lipase enzyme (CAS Reg. No. 9001-62-1), which is obtained from the...

  14. Hereditary chronic pancreatitis

    PubMed Central

    Rosendahl, Jonas; Bödeker, Hans; Mössner, Joachim; Teich, Niels

    2007-01-01

    Hereditary chronic pancreatitis (HCP) is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2), the serine protease inhibitor, Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) have been found to be associated with chronic pancreatitis (idiopathic and hereditary) as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer. PMID:17204147

  15. Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy.

    PubMed

    Tran, T C K; van 't Hof, G; Kazemier, G; Hop, W C; Pek, C; van Toorenenbergen, A W; van Dekken, H; van Eijck, C H J

    2008-01-01

    Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 microg/g (p < 0.0001), reflecting severe exocrine pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p < 0.0001). Neither pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively. Copyright 2008 S. Karger AG, Basel.

  16. [Chronic pancreatitis diagnosed after the first attack of acute pancreatitis].

    PubMed

    Bojková, Martina; Dítě, Petr; Uvírová, Magdalena; Dvořáčková, Nina; Kianička, Bohuslav; Kupka, Tomáš; Svoboda, Pavel; Klvaňa, Pavel; Martínek, Arnošt

    2016-02-01

    One of the diseases involving a potential risk of developing chronic pancreatitis is acute pancreatitis. Of the overall number of 231 individuals followed with a diagnosis of chronic pancreatitis, 56 patients were initially treated for acute pancreatitis (24.2 %). Within an interval of 12- 24 months from the first attack of acute pancreatitis, their condition gradually progressed to reached the picture of chronic pancreatitis. The individuals included in the study abstained (from alcohol) following the first attack of acute pancreatitis and no relapse of acute pancreatitis was proven during the period of their monitoring. The etiology of acute pancreatitis identified alcohol as the predominant cause (55.3 %), biliary etiology was proven in 35.7 %. According to the revised Atlanta classification, severe pancreatitis was established in 69.6 % of the patients, the others met the criterion for intermediate form, those with the light form were not included. Significant risk factors present among the patients were smoking, obesity and 18 %, resp. 25.8 % had pancreatogenous diabetes mellitus identified. 88.1 % of the patients with acute pancreatitis were smokers. The majority of individuals with chronic pancreatitis following an attack of acute pancreatitis were of a productive age from 25 to 50 years. It is not only acute alcoholic pancreatitis which evolves into chronic pancreatitis, we have also identified this transition for pancreatitis of biliary etiology.

  17. Enantioselective synthesis of (S)-naproxen using immobilized lipase on chitosan beads.

    PubMed

    Gilani, Saeedeh L; Najafpour, Ghasem D; Heydarzadeh, Hamid D; Moghadamnia, Aliakbar

    2017-06-01

    S-naproxen by enantioselective hydrolysis of racemic naproxen methyl ester was produced using immobilized lipase. The lipase enzyme was immobilized on chitosan beads, activated chitosan beads by glutaraldehyde, and Amberlite XAD7. In order to find an appropriate support for the hydrolysis reaction of racemic naproxen methyl ester, the conversion and enantioselectivity for all carriers were compared. In addition, effects of the volumetric ratio of two phases in different organic solvents, addition of cosolvent and surfactant, optimum pH and temperature, reusability, and inhibitory effect of methanol were investigated. The optimum volumetric ratio of two phases was defined as 3:2 of aqueous phase to organic phase. Various water miscible and water immiscible solvents were examined. Finally, isooctane was chosen as an organic solvent, while 2-ethoxyethanol was added as a cosolvent in the organic phase of the reaction mixture. The optimum reaction conditions were determined to be 35 °C, pH 7, and 24 h. Addition of Tween-80 in the organic phase increased the accessibility of immobilized enzyme to the reactant. The optimum organic phase compositions using a volumetric ratio of 2-ethoxyethanol, isooctane and Tween-80 were 3:7 and 0.1% (v/v/v), respectively. The best conversion and enantioselectivity of immobilized enzyme using chitosan beads activated by glutaraldehyde were 0.45 and 185, respectively. © 2017 Wiley Periodicals, Inc.

  18. [Biological disturbances during the lupus-associated pancreatitis: case report].

    PubMed

    Sayagh, Sanae; Benchekroun, Leila; Bouabdellah, Mounya; Jaouhar, Nezha; El Aoufi, Farida; El Oufir, Fatiha; Alaoui, Meryem; Adnaoui, Mohammed; Chabraoui, Layachi

    2015-01-01

    We report in this paper the case of female patient, hypertriglyceridemia associated with milky serum and hyperglycemia have been the alarm signal of a lupus-associated pancreatitis, the confirmation of this entity was done with elevated rate of serum lipase activity. It is about a 33 years age female. She has as unique antecedent a lupus diagnosed on January of the same. The patient was admitted on august 2013 for another episode of lupus associated to the lower lamb edema with a rate of C3 at 0.4 g/L (0.82-1,93) and C4 at 0.05 g/L (0.15-0.57). One day after the beginning of the corticotherapy, the patient presented hyperthermia, ataxis and behavior troubles, epigastric and articular pains and vomiting. Biochemical tests found hyperglycemia at 38.9 mmol/L (3.9-6.1), dyslipidemia with hypertriglyceridemia at 15.7 mmol/L (0.3-1.7) and total cholesterol rate at 5.2 mmol/L (<5.2) associated with milky serum. Haematological tests objective normocytic normochromic anemia with 81 g/L of hemoglobin, lymphopenia at 0.88 G/L and normal platelet rate. Lupus associated pancreatitis was suggested and confirmed biologically with an hyperlipasemia at 180 UI/L (8-78) and radiologicaly with the image of focal hepatic steatosis. We conclude that on the presence of lupus, gastrointestinal and/or biological signs must motivate the measurement of the serum lipase activity as quickly as possible to assess the diagnosis of lupus-associated pancreatitis.

  19. Hydrolysis of diacylglycerols by lipoprotein lipase.

    PubMed

    Morley, N H; Kuksis, A; Buchnea, D; Myher, J J

    1975-05-10

    Enantiomeric diacylglycerols were emulsified, mole for mole, with lyso(1-acyl) lecithin and were hydrolyzed with lipoprotein lipase in NH4Cl-beef serum albumin buffer at pH 8.6 after a brief incubation with delipidated rat serum. The enzyme was prepared from lyophilized and dialyzed bovine skim milk in a 4 percent solution. The course of hydrolysis for each set of enantiomers was determined by gas-liquid chromatography of the masses of the diacylglycerols remaining or monoacylglycerols released in the medium between 0 and 15 min. The majority of sets of sn-1,2- and 2,3-diacylglycerols, including an isotope-labeled true enantiomeric set which was assessed by mass spectrometry, demonstrated preference by the enzyme for lipolysis at position 1 but with less specificity than previously was shown in sn-triacylglycerol hydrolysis. The results preclude the possibility that the predominance of sn-2,3-diacylglycerol intermediates during triacylglycerol hydrolysis is due solely to a preferential breakdown of the 1,2-isomers and reinforce the conclusion that lipoprotein lipase is specific for position 1.

  20. Lysophosphatidylcholine synthesis by lipase-catalyzed ethanolysis.

    PubMed

    Yang, Guolong; Yang, Ruoxi; Hu, Jingbo

    2015-01-01

    Lysophosphatidylcholine (LPC) is amphiphilic substance, and possesses excellent physiological functions. In this study, LPC was prepared through ethanolysis of phosphatidylcholine (PC) in n-hexane or solvent free media catalyzed by Novozym 435 (from Candida antarctica), Lipozyme TLIM (from Thermomcyces lanuginosus) and Lipozyme RMIM (from Rhizomucor miehei). The results showed that three immobilized lipases from Candida Antarctica, Thermomcyces lanuginosus and Rhizomucor miehei could catalyze ethanolysis of PC efficiently. In n-hexane, the LPC conversions of ethanolysis of PC catalyzed by Novozyme 435, Lipozyme TLIM and Lipozyme RMIM could reach to 98.5 ± 1.6%, 94.6 ± 1.4% and 93.7 ± 1.8%, respectively. In solvent free media, the highest LPC conversions of ethanolysis of PC catalyzed by Novozyme 435, Lipozyme TL IM and Lipozyme RM IM were 97.7 ± 1.7%, 93.5 ± 1.2% and 93.8 ± 1.9%, respectively. The catalytic efficiencies of the three lipases were in the order of Novozyme 435 > Lipozyme TLIM > Lipozyme RMIM. Furthermore, their catalytic efficiencies in n-hexane were better than those in solvent free media.

  1. Bioremediation of cooking oil waste using lipases from wastes

    PubMed Central

    do Prado, Débora Zanoni; Facanali, Roselaine; Marques, Márcia Mayo Ortiz; Nascimento, Augusto Santana; Fernandes, Célio Junior da Costa; Zambuzzi, William Fernando

    2017-01-01

    Cooking oil waste leads to well-known environmental impacts and its bioremediation by lipase-based enzymatic activity can minimize the high cytotoxic potential. In addition, they are among the biocatalysts most commercialized worldwide due to the versatility of reactions and substrates. However, although lipases are able to process cooking oil wastes, the products generated from this process do not necessarily become less toxic. Thus, the aim of the current study is to analyze the bioremediation of lipase-catalyzed cooking oil wastes, as well as their effect on the cytotoxicity of both the oil and its waste before and after enzymatic treatment. Thus, assessed the post-frying modification in soybean oil and in its waste, which was caused by hydrolysis reaction catalyzed by commercial and home-made lipases. The presence of lipases in the extracts obtained from orange wastes was identified by zymography. The profile of the fatty acid esters formed after these reactions was detected and quantified through gas chromatography and fatty acids profile compared through multivariate statistical analyses. Finally, the soybean oil and its waste, with and without enzymatic treatment, were assessed for toxicity in cytotoxicity assays conducted in vitro using fibroblast cell culture. The soybean oil wastes treated with core and frit lipases through transesterification reaction were less toxic than the untreated oils, thus confirming that cooking oil wastes can be bioremediated using orange lipases. PMID:29073166

  2. [Immobilization of Candida sp. lipase on resin D301].

    PubMed

    Wang, Yanhua; Zhu, Kai; Liu, Hui; Han, Pingfang; Wei, Ping

    2009-12-01

    We immobilized Candida sp. lipase onto seven kinds of industrial adsorption and ion exchange resins. By determining the activity of each immobilized enzyme, the weakly basic anionic exchange resin of D301 showed the best results for the immobilization of Candida sp. lipase. Comparing the scanning electron micrographs of D301 with Novozym 435 (immobilized Candida antarctica lipase B from Novo Nordisk Corp.), we selected D301 as a carrier for the immobilization of Candida sp. lipase. And we pretreated the resin D301 with the bifunctional agent glutaraldehyde and crosslinked it with Candida sp. lipase. The optimal conditions for the immobilization of Candida sp. lipase were as follows: 8 mL of the amount of 5% glutaraldehyde solution, five hours of the time pretreated D301 with glutaraldehyde, 1.0 g/L the concentration of Candida sp. lipase used, pH of the phosphate buffered, 6.0 and 10 hours of time for immobilization, respectively. The activity of immobilized enzyme was over 35 U/mg and the efficiency of immobilization was around 3.5 Ul(mg x h).

  3. Bioremediation of cooking oil waste using lipases from wastes.

    PubMed

    Okino-Delgado, Clarissa Hamaio; Prado, Débora Zanoni do; Facanali, Roselaine; Marques, Márcia Mayo Ortiz; Nascimento, Augusto Santana; Fernandes, Célio Junior da Costa; Zambuzzi, William Fernando; Fleuri, Luciana Francisco

    2017-01-01

    Cooking oil waste leads to well-known environmental impacts and its bioremediation by lipase-based enzymatic activity can minimize the high cytotoxic potential. In addition, they are among the biocatalysts most commercialized worldwide due to the versatility of reactions and substrates. However, although lipases are able to process cooking oil wastes, the products generated from this process do not necessarily become less toxic. Thus, the aim of the current study is to analyze the bioremediation of lipase-catalyzed cooking oil wastes, as well as their effect on the cytotoxicity of both the oil and its waste before and after enzymatic treatment. Thus, assessed the post-frying modification in soybean oil and in its waste, which was caused by hydrolysis reaction catalyzed by commercial and home-made lipases. The presence of lipases in the extracts obtained from orange wastes was identified by zymography. The profile of the fatty acid esters formed after these reactions was detected and quantified through gas chromatography and fatty acids profile compared through multivariate statistical analyses. Finally, the soybean oil and its waste, with and without enzymatic treatment, were assessed for toxicity in cytotoxicity assays conducted in vitro using fibroblast cell culture. The soybean oil wastes treated with core and frit lipases through transesterification reaction were less toxic than the untreated oils, thus confirming that cooking oil wastes can be bioremediated using orange lipases.

  4. Lipase production in lipolytic yeast from Wonorejo mangrove area

    NASA Astrophysics Data System (ADS)

    Alami, Nur Hidayatul; Nasihah, Liziyatin; Umar, Rurin Luswidya Artaty; Kuswytasari, Nengah Dwianita; Zulaika, Enny; Shovitri, Maya

    2017-06-01

    Lipase is an enzyme that is often used in industry and become a commercial enzyme. One group of microorganisms capable of producing lipase is a yeast. This study aims to screen yeast from Wonorejo mangrove that potential to produce lipase and to optimize the production of these enzymes. Screening test include the measurement of lipolytic index and value of fatty acid. Yeast with the best value of fatty acid will be continued to the measurement of lipase activity. It is affected by several environmental factors, such as pH, temperature, and incubation time. This research was conducted to observe the optimization variation on environmental factors combination to produce lipase. Lipase activity was tested by using p-Nitrophenyl Palmitate (pNPP). Absorbency was measured by spectrofotometer on wavelength of 410 nm. Measurement of the enzyme activity was done by interpolating the absorbance values on the p-nitrophenol standard curve then calculated by the formula. All data were analyzed by using descriptive quantitative method. The results show that the highest lypolityc index was 2.08. The highest value of fatty acid was 0.49 that was reached on 168 hours of incubation. Candida W3.8 expressed the highest lypolylitic potential. The optimum environment to produce lipase by Candida W 3.8 was on 120 hours of incubation time, in temperature range of 27°C - 45°C and pH range of 4,5 - 7.

  5. Effects of culinary spices and psychological stress on postprandial lipemia and lipase activity: results of a randomized crossover study and in vitro experiments.

    PubMed

    McCrea, Cindy E; West, Sheila G; Kris-Etherton, Penny M; Lambert, Joshua D; Gaugler, Trent L; Teeter, Danette L; Sauder, Katherine A; Gu, Yeyi; Glisan, Shannon L; Skulas-Ray, Ann C

    2015-01-16

    Data suggest that culinary spices are a potent, low-calorie modality for improving physiological responses to high fat meals. In a pilot study (N = 6 healthy adults), we showed that a meal containing a high antioxidant spice blend attenuated postprandial lipemia by 30% compared to a low spice meal. Our goal was to confirm this effect in a larger sample and to consider the influence of acute psychological stress on fat metabolism. Further, we used in vitro methods to evaluate the inhibitory effect of spices on digestive enzymes. In a 2 x 2, randomized, 4-period crossover design, we compared the effects of 14.5 g spices (black pepper, cinnamon, cloves, garlic, ginger, oregano, paprika, rosemary, and turmeric) vs. placebo incorporated into a high fat meal (1000 kcal, 45 g fat), followed by psychological stress (Trier Social Stress Test) vs. rest on postprandial metabolism in 20 healthy but overweight adults. Blood was sampled at baseline and at 105, 140, 180, and 210 minutes for analysis of triglycerides, glucose, and insulin. Additional in vitro analyses examined the effect of the spice blend and constituent spices on the activity of pancreatic lipase (PL) and secreted phospholipase A₂ (PLA₂). Mixed models were used to model the effects of spices and stress (SAS v9.3). Serum triglycerides, glucose and insulin were elevated following the meal (p < 0.01). Spices reduced post-meal triglycerides by 31% when the meal was followed by the rest condition (p = 0.048), but this effect was not present during stress. There was no effect of the spice blend on glucose or insulin; however, acute stress significantly increased both of these measures (p < 0.01; mean increase of 47% and 19%, respectively). The spice blend and several of the individual spices dose-dependently inhibited PL and PLA2 activity in vitro. Inclusion of spices may attenuate postprandial lipemia via inhibition of PL and PLA₂. However, the impact of psychological stress negates any

  6. Increased plasma pancreatic polypeptide in chronic alcohol abuse.

    PubMed

    Fink, R S; Adrian, T E; Margot, D H; Bloom, S R

    1983-04-01

    Post-prandial plasma gastrointestinal hormone profiles were measured in nine chronic alcoholics, one and fourteen days after complete alcohol withdrawal. Basal plasma pancreatic polypeptide concentration (PP--mean +/- SE mean) was significantly greater in alcoholics (control, 28 +/- 5 pmol/l; alcoholics, post-withdrawal day 1, 62 +/- 14 pmol/l, P less than 0.05; and post-withdrawal day 14, 89 +/- 17 pmol/1, P less than 0.005). The total integrated (TIR) PP response following a test breakfast was similarly elevated (control, 442 +/- 63 units; alcoholics, day 1, 1310 +/- 231 units, P less than 0.005; day 14,1066 +/- 66, P less than 0.005). Basal and TIR values for gastrin, gastric inhibitory peptide, insulin and glucagon were similar in alcoholics and controls. As PP has been shown to inhibit pancreatic exocrine enzyme secretion, these findings may help explain the abnormal pancreatic function seen frequently in alcoholics.

  7. Latest advances in chronic pancreatitis.

    PubMed

    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.

  8. Acute Pancreatitis in Children.

    PubMed

    Werlin, Steven L.

    2001-10-01

    There are no drugs that cure or abate pancreatitis. The treatment of patients with mild and moderate episodes of pancreatitis (85%) is supportive and expectant. Central issues include the removal of the initiating process (if possible), relief of pain, and maintenance of fluid and electrolyte balance. Endoscopic retrograde cholangiopancreatography may be required for stone extraction in patients with biliary pancreatitis. Surgery is rarely required. The aims of treatment for patients with severe disease includes treatment of local, systemic, and septic complications in addition to those for mild and moderate disease. Homeostasis is maintained by the correction of hypocalcemia, anemia, hypoalbuminemia, electrolyte imbalances, and hypoxemia. A large number of medications have been used unsuccessfully in an attempt to halt the progression of the autodigestive process within the pancreas and to reduce pancreatic secretions. Nutritional support with either enteral or parenteral feeding is given. Intravenous antibiotics or selective bowel decontamination decrease mortality in patients with severe episodes of pancreatitis. The treatment for these individuals is often prolonged. Surgical treatment of traumatic pancreatitis with ductal rupture includes repair or resection. At times, simple drainage is performed and definitive surgery is deferred until later. Surgical treatment of severe pancreatitis includes debridement of necrotic and infected tissue. The emerging consensus appears to be that necrosectomy and local lavage or open management with planned re-exploration offers better survival than the conventional therapy of resection plus drainage alone.

  9. Protective effect of Mimosa pudica L. in an L-arginine model of acute necrotising pancreatitis in rats.

    PubMed

    Kaur, Jagdeep; Sidhu, Shabir; Chopra, Kanwaljit; Khan, M U

    2016-07-01

    Mimosa pudica is used in traditional medicine for treating various disorders such as inflammatory conditions, diarrhoea, insomnia, alopecia, urogenital infections and wounds. The present study investigated the effect of M. pudica extract (MPE) on L-arginine-induced acute necrotising pancreatitis in rats. The ethanolic extract of M. pudica leaves was studied for the presence of quercetin and gallic acid using high-performance liquid chromatography. Four groups were employed-normal control rats, L-arginine control rats (two intraperitoneal [i.p.] injections of 2 g/kg at an interval of 1 h), MPE-treated rats (400 mg/kg orally) and melatonin-treated rats (positive control 10 mg/kg i.p.), which were further divided into subgroups according to time points (24 h, 3 days and 14 days). Serum amylase, lipase, tumour necrosis factor-α (TNF-α), pancreatic amylase, nucleic acid content, protein, transforming growth factor-β1 (TGF-β1), thiobarbituric reactive substances, glutathione, nitrite/nitrate, collagen content and histopathological examination were carried out. MPE significantly improved acute necrotising pancreatitis by modulating diagnostic markers of pancreatitis such as serum lipase and pancreatic amylase, inflammation (TNF-α), and oxidative and nitrosative stress. Moreover, MPE administration induced regenerative changes in the pancreas evidenced by increased levels of pancreatic proteins, nucleic acid content and histopathology report. In addition, MPE improved TGF-β1 and collagen levels thereby preventing fibrosis. The current investigation indicates the novel role of MPE in reducing the severity of acute necrotising pancreatitis by plausible mechanisms such as anti-inflammatory and anti-fibrotic activity and by promoting repair and regeneration of the pancreas.

  10. Extracts from the edible seaweed, Ascophyllum nodosum, inhibit lipase activity in vitro: contributions of phenolic and polysaccharide components.

    PubMed

    Austin, Ceri; Stewart, Derek; Allwood, J William; McDougall, Gordon J

    2018-01-24

    A polyphenol-rich extract (PRE) from the edible seaweed, Ascophyllum nodosum, inhibited pancreatic lipase activity in an oil-based turbidimetric assay with an IC 50 of 200 μg gallic acid equivalents (GAE) perassay) [∼230 μg DW] whereas the known inhibitor, Orlistat, gave an IC 50 at 0.4 μg per assay. A phlorotannin-enriched fraction (TRF) purified from the PRE was more potent with an IC 50 = 60 μg GAE per assay (∼65 μg DW). When the assay was started by the addition of lipase, both Orlistat and TRF were much less effective which suggests that pre-incubation of enzyme and inhibitor improved inhibition. Based on phenol content, water extracts from Ascophyllum were more potent lipase inhibitors than PRE (IC 50 ∼ 150 μg GAE per assay). However, this was equivalent to ∼580 μg DW and these extracts contained polysaccharides (e.g. alginate content = 110 μg mL -1 ) which may also contribute to inhibition. Indeed, a polysaccharide-enriched fraction obtained by ethanol precipitation gave an IC 50 of 1000 μg DW which was equivalent to 130 μg GAE and 420 μg alginate per assay. Therefore a >3 fold increase in alginate content did not markedly improve inhibition. Re-precipitation increased alginate content and reduced polyphenol content but lipase inhibition was markedly reduced (i.e. IC 50 at ∼1100 μg DW per assay, 700 μg alginate and 25 μg GAE). Purifying the polysaccharide fraction by ion exchange removed all phenolics but the IC 50 increased to >2500 μg DW, equivalent to >1970 μg alginate per assay. In conclusion, polysaccharides and phlorotannins may inhibit lipase in an additive fashion, with phlorotannins apparently more effective in vitro. However, interactions between these components may be important when food products containing this edible seaweed are consumed.

  11. PKD signaling and pancreatitis

    PubMed Central

    Yuan, Jingzhen; Pandol, Stephen J.

    2016-01-01

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

  12. [Acute pancreatitis and afferent loop syndrome. Case report].

    PubMed

    Barajas-Fregoso, Elpidio Manuel; Romero-Hernández, Teodoro; Macías-Amezcua, Michel Dassaejv

    2013-01-01

    The afferent syndrome loop is a mechanic obstruction of the afferent limb before a Billroth II or Roux-Y reconstruction, secondary in most of case to distal or subtotal gastrectomy. Clinical case: Male 76 years old, with antecedent of cholecystectomy, gastric adenocarcinoma six years ago, with subtotal gastrectomy and Roux-Y reconstruction. Beginning a several abdominal pain, nausea and vomiting, abdominal distension, without peritoneal irritation sings. Amylase 1246 U/L, lipase 3381 U/L. Computed Tomography with thickness wall and dilatation of afferent loop, pancreas with diffuse enlargement diagnostic of acute pancreatitis secondary an afferent loop syndrome. The afferent loop syndrome is presented in 0.3%-1% in all cases with Billroth II reconstruction, with a mortality of up to 57%, the obstruction lead accumulation of bile, pancreatic and intestinal secretions, increasing the pressure and resulting in afferent limb, bile conduct and Wirsung conduct dilatation, triggering an inflammatory response that culminates in pancreatic inflammation. The severity of the presentation is related to the degree and duration of the blockage.

  13. Clinical signs of pancreatitis.

    PubMed

    Penny, Steven M

    2012-01-01

    The pancreas consists of complex structures that perform vital functions. Radiologic technologists must comprehend its normal structure and function to perform functional imaging procedures in their daily practice, as well as to know how any deviation from normalcy can disrupt homeostasis. Because pancreatitis is a potentially life-threatening disease, a thorough understanding of the clinical manifestation and imaging characteristics of the various forms of the disease is crucial. This article reviews distinctive pancreatic function and discusses basic pancreas imaging. In addition, acute and chronic pancreatitis is explored, including the role of medical imaging in its diagnosis, complications, and prognosis.

  14. Bioreactors with immobilized lipases: state of the art.

    PubMed

    Balcão, V M; Paiva, A L; Malcata, F X

    1996-05-01

    This review attempts to provide an updated compilation of studies reported in the literature pertaining to reactors containing lipases in immobilized forms, in a way that helps the reader direct a bibliographic search and develop an integrated perspective of the subject. Highlights are given to industrial applications of lipases (including control and economic considerations), as well as to methods of immobilization and configurations of reactors in which lipases are used. Features associated with immobilized lipase kinetics such as enzyme activities, adsorption properties, optimum operating conditions, and estimates of the lumped parameters in classical kinetic formulations (Michaelis-Menten model for enzyme action and first-order model for enzyme decay) are presented in the text in a systematic tabular form.

  15. Endothelial lipase is a major determinant of HDL level

    SciTech Connect

    Ishida, Tatsuro; Choi, Sungshin; Kundu, Ramendra K.

    2003-01-30

    For the past three decades, epidemiologic studies have consistently demonstrated an inverse relationship between plasma HDL cholesterol (HDL-C) concentrations and coronary heart disease (CHD). Population-based studies have provided compelling evidence that low HDL-C levels are a risk factor for CHD, and several clinical interventions that increased plasma levels of HDL-C were associated with a reduction in CHD risk. These findings have stimulated extensive investigation into the determinants of plasma HDL-C levels. Turnover studies using radiolabeled apolipoprotein A-I, the major protein component of HDL, suggest that plasma HDL-C concentrations are highly correlated with the rate of clearance of apolipoprotein AI. However,more » the metabolic mechanisms by which HDL are catabolized have not been fully defined. Previous studies in humans with genetic deficiency of cholesteryl ester transfer protein, and in mice lacking the scavenger receptor BI (SR-BI), have demonstrated that these proteins participate in the removal of cholesterol from HDL, while observations in individuals with mutations in hepatic lipase indicate that this enzyme hydrolyzes HDL triglycerides. In this issue of the JCI, reports from laboratories of Tom Quertermous and Dan Rader now indicate that endothelial lipase (LIPG), a newly identified member of the lipase family, catalyzes the hydrolysis of HDL phospholipids and facilitates the clearance of HDL from the circulation. Endothelial lipase was initially cloned by both of these laboratories using entirely different strategies. Quertermous and his colleagues identified endothelial lipase as a transcript that was upregulated in cultured human umbilical vein endothelial cells undergoing tube formation, whereas the Rader group cloned endothelial lipase as a transcript that was upregulated in the human macrophage-like cell line THP-1 exposed to oxidized LDL. Database searches revealed that endothelial lipase shows strong sequence similarity to

  16. Monoacylglycerol lipase – a target for drug development?

    PubMed Central

    Fowler, CJ

    2012-01-01

    The endocannabinoid (eCB) system is involved in processes as diverse as control of appetite, perception of pain and the limitation of cancer cell growth and invasion. The enzymes responsible for eCB breakdown are attractive pharmacological targets, and fatty acid amide hydrolase inhibitors, which potentiate the levels of the eCB anandamide, are now undergoing pharmaceutical development. ‘Drugable’ selective inhibitors of monoacylglycerol lipase, a key enzyme regulating the levels of the other main eCB, 2-arachidonoylglycerol, were however not identified until very recently. Their availability has resulted in a large expansion of our knowledge concerning the pharmacological consequences of monoacylglycerol lipase inhibition and hence the role(s) played by the enzyme in the body. In this review, the pharmacology of monoacylglycerol lipase will be discussed, together with an analysis of the therapeutic potential of monoacylglycerol lipase inhibitors as analgesics and anticancer agents. PMID:22428756

  17. Pancreatic cellular injury after cardiac surgery with cardiopulmonary bypass: frequency, time course and risk factors.

    PubMed

    Nys, Monique; Venneman, Ingrid; Deby-Dupont, Ginette; Preiser, Jean-Charles; Vanbelle, Sophie; Albert, Adelin; Camus, Gérard; Damas, Pierre; Larbuisson, Robert; Lamy, Maurice

    2007-05-01

    Although often clinically silent, pancreatic cellular injury (PCI) is relatively frequent after cardiac surgery with cardiopulmonary bypass; and its etiology and time course are largely unknown. We defined PCI as the simultaneous presence of abnormal values of pancreatic isoamylase and immunoreactive trypsin (IRT). The frequency and time evolution of PCI were assessed in this condition using assays for specific exocrine pancreatic enzymes. Correlations with inflammatory markers were searched for preoperative risk factors. One hundred ninety-three patients submitted to cardiac surgery were enrolled prospectively. Blood IRT, amylase, pancreatic isoamylase, lipase, and markers of inflammation (alpha1-protease inhibitor, alpha2-macroglobulin, myeloperoxidase) were measured preoperatively and postoperatively until day 8. The postoperative increase in plasma levels of pancreatic enzymes and urinary IRT was biphasic in all patients: early after surgery and later (from day 4 to 8 after surgery). One hundred thirty-three patients (69%) experienced PCI, with mean IRT, isoamylase, and alpha1-protease inhibitor values higher for each sample than that in patients without PCI. By multiple regression analysis, we found preoperative values of plasma IRT >or=40 ng/mL, amylase >or=42 IU/mL, and pancreatic isoamylase >or=20 IU/L associated with a higher incidence of postsurgery PCI (P < 0.005). In the PCI patients, a significant correlation was found between the 4 pancreatic enzymes and urinary IRT, total calcium, myeloperoxidase, alpha1-protease inhibitor, and alpha2-macroglobulin. These data support a high prevalence of postoperative PCI after cardiac surgery with cardiopulmonary bypass, typically biphasic and clinically silent, especially when pancreatic enzymes were elevated preoperatively.

  18. Immobilization of Yarrowia lipolytica Lipase on Macroporous Resin Using Different Methods: Characterization of the Biocatalysts in Hydrolysis Reaction.

    PubMed

    Sun, Jingjing; Chen, Yiling; Sheng, Jun; Sun, Mi

    2015-01-01

    To improve the reusability and organic solvent tolerance of microbial lipase and expand the application of lipase (hydrolysis, esterification, and transesterification), we immobilized marine microbial lipase using different methods and determined the properties of immobilized lipases. Considering the activity and cost of immobilized lipase, the concentration of lipase was fixed at 2 mg/mL. The optimal temperature of immobilized lipases was 40°C and 5°C higher than free lipase. The activities of immobilized lipases were much higher than free lipase at alkaline pH (more than 50% at pH 12). The free lipase lost most activity (35.3%) and immobilized lipases retained more than 46.4% of their initial activity after 3 h heat treatment at 70°C. At alkaline pH, immobilized lipases were more stable than free lipase (more than 60% residue activity at pH 11 for 3 h). Immobilized lipases retained 80% of their activity after 5 cycles and increased enzyme activity (more than 108.7%) after 3 h treatment in tert-butanol. Immobilization of lipase which improved reusability of lipase and provided a chance to expand the application of marine microbial lipase in organic system expanded the application range of lipase to catalyze hydrolysis and esterification in harsh condition.

  19. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez Muñoz, J Enrique

    2015-09-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the treatment of symptoms and complications, mainly pain and pancreatic exocrine insufficiency, and the diagnosis and therapy of autoimmune pancreatitis. The multimodal dynamic endoscopic ultrasound-guided secretin-stimulated evaluation of the pancreas provides relevant morphological and functional information for the diagnosis of chronic pancreatitis at early stages. Extracorporeal shock wave lithotripsy in patients with calcifying pancreatitis and endoscopic pancreatic stent placement are effective alternatives for pain therapy in patients with chronic pancreatitis. Presence of pancreatic exocrine insufficiency in patients with chronic pancreatitis is associated with a significantly increase of mortality rate. Despite that, pancreatic enzyme replacement therapy is not prescribed in the majority of patients with pancreatic exocrine insufficiency, or it is prescribed at a low dose. The newly developed and commercialized needles for endoscopic ultrasound-guided pancreatic biopsy are effective in retrieving appropriate tissue samples for the histological diagnosis of autoimmune pancreatitis. Maintenance therapy with azathioprine is effective and safe to prevent relapses in patients with autoimmune pancreatitis. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  20. The role of apelin in the modulation of gastric and pancreatic enzymes activity in adult rats.

    PubMed

    Antuschevich, H; Kapica, M; Krawczynska, A; Herman, A; Kato, I; Kuwahara, A; Zabielski, R

    2016-06-01

    Apelin is considered as important gut regulatory peptide ligand of APJ receptor with a potential physiological role in gastrointestinal cytoprotection, regulation of food intake and drinking behavior. Circulating apelin inhibits secretion of pancreatic juice through vagal- cholecystokinin-dependent mechanism and reduces local blood flow. Our study was aimed to determine the effect of fundectomy and intraperitoneal or intragastric administration of apelin-13 on pancreatic and gastric enzymes activities in adult rats. Fundectomy is a surgical removal of stomach fundus - maine site apelin synthesis. Three independent experiments were carried out on Wistar rats. In the first and second experiment apelin-13 was given by intragastric or intraperitoneal way twice a day for 10 days (100 nmol/kg b.w.). Control groups received the physiological saline respectively. In the third experiment the group of rats after fundectomy were used. Fundectomized rats did not receive apelin and the rats from control group were 'sham operated'. At the end of experiment rats were sacrificed and blood from rats was withdrawn for apelin and CCK (cholecystokinin) radioimmunoassay analysis and pancreas and stomach tissues were collected for enzyme activity analyses. Intragastric and intraperitoneal administrations of apelin-13 increased basal plasma CCK level and stimulated gastric and pancreatic enzymes activity in rats. In animals after fundectomy decreased activity of studied enzymes was observed, as well as basal plasma apelin and CCK levels. In conclusion, apelin can effects on CCK release and stimulates some gastric and pancreatic enzymes activity in adult rats while fudectomy suppresses those processes. Changes in the level of pancreatic lipase activity point out that apelin may occurs as a regulator of lipase secretion.

  1. S5 Lipase: an organic solvent tolerant enzyme.

    PubMed

    Rahman, Raja Noor Zaliha Abdul; Baharum, Syarul Nataqain; Salleh, Abu Bakar; Basri, Mahiran

    2006-12-01

    In this study, an organic solvent tolerant bacterial strain was isolated. This strain was identified as Pseudomonas sp. strain S5, and was shown to degrade BTEX (Benzene, Toluene, Ethyl-Benzene, and Xylene). Strain S5 generates an organic solvent-tolerant lipase in the late logarithmic phase of growth. Maximum lipase production was exhibited when peptone was utilized as the sole nitrogen source. Addition of any of the selected carbon sources to the medium resulted in a significant reduction of enzyme production. Lower lipase generation was noted when an inorganic nitrogen source was used as the sole nitrogen source. This bacterium hydrolyzed all tested triglycerides and the highest levels of production were observed when olive oil was used as a natural triglyceride. Basal medium containing Tween 60 enhanced lipase production to the most significant degree. The absence of magnesium ions (Mg2+) in the basal medium was also shown to stimulate lipase production. Meanwhile, an alkaline earth metal ion, Na+, was found to stimulate the production of S5 lipase.

  2. Effects of surfactants on lipase structure, activity, and inhibition.

    PubMed

    Delorme, Vincent; Dhouib, Rabeb; Canaan, Stéphane; Fotiadu, Frédéric; Carrière, Frédéric; Cavalier, Jean-François

    2011-08-01

    Lipase inhibitors are the main anti-obesity drugs prescribed these days, but the complexity of their mechanism of action is making it difficult to develop new molecules for this purpose. The efficacy of these drugs is known to depend closely on the physico-chemistry of the lipid-water interfaces involved and on the unconventional behavior of the lipases which are their target enzymes. The lipolysis reaction which occurs at an oil-water interface involves complex equilibria between adsorption-desorption processes, conformational changes and catalytic mechanisms. In this context, surfactants can induce significant changes in the partitioning of the enzyme and the inhibitor between the water phase and lipid-water interfaces. Surfactants can be found at the oil-water interface where they compete with lipases for adsorption, but also in solution in the form of micellar aggregates and monomers that may interact with hydrophobic parts of lipases in solution. These various interactions, combined with the emulsification and dispersion of insoluble substrates and inhibitors, can either promote or decrease the activity and the inhibition of lipases. Here, we review some examples of the various effects of surfactants on lipase structure, activity and inhibition, which show how complex the various equilibria involved in the lipolysis reaction tend to be.

  3. Pancreatic islet cell tumor

    MedlinePlus

    ... JH, Kastan MB, Tepper JE, eds. Abeloff's Clinical Oncology . 5th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap ... Cancer Network website. NCCN clinical practice guidelines in oncology (NCCN guidelines): pancreatic adenocarcinoma. Version 3.2017. www. ...

  4. Hypermutation In Pancreatic Cancer.

    PubMed

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

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

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

    PubMed

    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.

  6. Endoscopic pancreatic necrosectomy.

    PubMed

    Fogel, Evan L

    2011-07-01

    Traditionally, patients with symptomatic sterile pancreatic necrosis or infected necrosis have been managed by open surgical debridement and removal of necrotic tissue. Within the last decade, however, reports of endoscopic pancreatic necrosectomy, an alternative minimally invasive approach, have demonstrated high success rates and low mortality rates. This report describes the indications, technique, and study outcome data of the procedure. While our experience with this technique has recently increased, better selection criteria are needed to identify patients who are most suitable for endoscopic therapy.

  7. Management of pancreatic trauma.

    PubMed

    Girard, E; Abba, J; Arvieux, C; Trilling, B; Sage, P Y; Mougin, N; Perou, S; Lavagne, P; Létoublon, C

    2016-08-01

    Pancreatic trauma (PT) is associated with high morbidity and mortality; the therapeutic options remain debated. Retrospective study of PT treated in the University Hospital of Grenoble over a 22-year span. The decision for initial laparotomy depended on hemodynamic status as well as on associated lesions. Main pancreatic duct lesions were always searched for. PT lesions were graded according to the AAST classification. Of a total of 46 PT, 34 were grades II or I. Hemodynamic instability led to immediate laparotomy in 18 patients, for whom treatment was always drainage of the pancreatic bed; morbidity was 30%. Eight patients had grade III injuries, six of whom underwent immediate operation: three underwent splenopancreatectomy without any major complications while the other three who had simple drainage required re-operation for peritonitis, with one death related to pancreatic complications. Four patients had grades IV or V PT: two pancreatoduodenectomies were performed, with no major complication, while one patient underwent duodenal reconstruction with pancreatic drainage, complicated by pancreatic and duodenal fistula requiring a hospital stay of two months. The post-trauma course was complicated for all patients with main pancreatic duct involvement. Our outcomes were similar to those found in the literature. In patients with distal PT and main pancreatic duct involvement, simple drainage is associated with high morbidity and mortality. For proximal PT, the therapeutic options of drainage versus pancreatoduodenectomy must be weighed; pancreatoduodenectomy may be unavoidable when the duodenum is injured as well. Two-stage (resection first, reconstruction later) could be an effective alternative in the emergency setting when there are other associated traumatic lesions. Copyright © 2016. Published by Elsevier Masson SAS.

  8. The Role of Nutraceuticals in Pancreatic Cancer Prevention and Therapy: Targeting Cellular Signaling, MicroRNAs, and Epigenome.

    PubMed

    Li, Yiwei; Go, Vay Liang W; Sarkar, Fazlul H

    2015-01-01

    Pancreatic cancer is one of the most aggressive malignancies in US adults. Experimental studies have found that antioxidant nutrients could reduce oxidative DNA damage, suggesting that these antioxidants may protect against pancreatic carcinogenesis. Several epidemiologic studies showed that dietary intake of antioxidants was inversely associated with the risk for pancreatic cancer, demonstrating the inhibitory effects of antioxidants on pancreatic carcinogenesis. Moreover, nutraceuticals, the anticancer agents from diet or natural plants, have been found to inhibit the development and progression of pancreatic cancer through the regulation of cellular signaling pathways. Importantly, nutraceuticals also up-regulate the expression of tumor-suppressive microRNAs (miRNAs) and down-regulate the expression of oncogenic miRNAs, leading to the inhibition of pancreatic cancer cell growth and pancreatic cancer stem cell self-renewal through modulation of cellular signaling network. Furthermore, nutraceuticals also regulate epigenetically deregulated DNAs and miRNAs, leading to the normalization of altered cellular signaling in pancreatic cancer cells. Therefore, nutraceuticals could have much broader use in the prevention and/or treatment of pancreatic cancer in combination with conventional chemotherapeutics. However, more in vitro mechanistic experiments, in vivo animal studies, and clinical trials are needed to realize the true value of nutraceuticals in the prevention and/or treatment of pancreatic cancer.

  9. The role of nutraceuticals in pancreatic cancer prevention and therapy: Targeting cellular signaling, miRNAs and epigenome

    PubMed Central

    Li, Yiwei; Go, Vay Liang W.; Sarkar, Fazlul H.

    2014-01-01

    Pancreatic cancer is one of the most aggressive malignancies in US adults. The experimental studies have found that antioxidant nutrients could reduce oxidative DNA damage, suggesting that these antioxidants may protect against pancreatic carcinogenesis. Several epidemiologic studies showed that dietary intake of antioxidants was inversely associated with the risk of pancreatic cancer, demonstrating the inhibitory effects of antioxidants on pancreatic carcinogenesis. Moreover, nutraceuticals, the anti-cancer agents from diet or natural plants, have been found to inhibit the development and progression of pancreatic cancer through the regulation of cellular signaling pathways. Importantly, nutraceuticals also up-regulate the expression of tumor suppressive miRNAs and down-regulate the expression of oncogenic miRNAs, leading to the inhibition of pancreatic cancer cell growth and pancreatic Cancer Stem Cell (CSC) self-renewal through modulation of cellular signaling network. Furthermore, nutraceuticals also regulate epigenetically deregulated DNAs and miRNAs, leading to the normalization of altered cellular signaling in pancreatic cancer cells. Therefore, nutraceuticals could have much broader use in the prevention and/or treatment of pancreatic cancer in combination with conventional chemotherapeutics. However, more in vitro mechanistic experiments, in vivo animal studies, and clinical trials are needed to realize the true value of nutraceuticals in the prevention and/or treatment of pancreatic cancer. PMID:25493373

  10. Protective effect of chlorogenic acid on the inflammatory damage of pancreas and lung in mice with l-arginine-induced pancreatitis.

    PubMed

    Ohkawara, Tatsuya; Takeda, Hiroshi; Nishihira, Jun

    2017-12-01

    Pancreatitis is characterized by inflammatory disease with severe tissue injury in pancreas, and the incidence of pancreatitis has been recently increasing. Although several treatments of acute pancreatitis have been developed, some patients have been resistant to current therapy. Chlorogenic acid (CGA) is one of the polyphenols, and is known to have an anti-inflammatory effect. In this study, we investigated the effects of CGA on experimental pancreatitis in mice. Pancreatitis was induced by twice injection of l-arginine (5g/kg body weight). Mice were intraperitoneally injected with CGA (20mg/kg or 40mg/kg) 1h before administration of l-arginine. Administration of 40mg/kg of CGA decreased the histological severity of pancreatitis and pancreatitis-associated lung injury. Moreover, administration of CGA inhibited the levels of pancreatic enzyme activity. Interestingly, CGA reduced the serum and pancreatic levels of macrophage migration inhibitory factor (MIF) in mice with l-arginine-induced pancreatitis. Our results suggest that CGA has an anti-inflammatory effect on l-arginine-induced pancreatitis and pancreatitis-associated lung injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Iatrogenic acute pancreatitis due to hypercalcemia in a child with pseudohypoparathyroidism.

    PubMed

    Feyles, Francesca; Mussa, Alessandro; Peiretti, Valentina; Tessaris, Daniele; Santanera, Arianna; Corrias, Andrea; de Sanctis, Luisa; Calvo, Luigi

    2014-01-01

    Pancreatitis due to hypercalcemia is very rare in children, and its pathogenetic role is still debated. The following report describes a case of acute pancreatitis secondary to hypercalcemia in a 6-year-old boy with pseudohypoparathyroidism treated with calcium and vitamin D. Pseudohypoparathyroidism is characterized by parathormone (PTH) resistance, high PTH levels and hypocalcemia which need to be corrected with calcium and vitamin D supplementation. The patient was admitted for severe abdominal pain and vomiting associated with high plasma amylase, lipase and calcium levels. Hypercalcemia due to vitamin D and calcium overtreatment was probably responsible for the acute pancreatitis in this case. High serum calcium levels seem to sensitize patients to pancreatitis, even if the mechanism through which it happens is not completely understood. Moreover, the importance of concomitant predisposing factors, either acquired or especially genetic, needs to be further defined. Even though a rare occurance in childhood, hypercalcemia should be considered as a cause of pancreatitis and it should be examined together with the other etiologies that may contribute to the development of this disease.

  12. Indomethacin inhabits the NLRP3 inflammasome pathway and protects severe acute pancreatitis in mice.

    PubMed

    Lu, Guotao; Pan, Yiyuan; Kayoumu, Abudurexiti; Zhang, Ling; Yin, Tao; Tong, Zhihui; Li, Baiqiang; Xiao, Weiming; Ding, Yanbing; Li, Weiqin

    2017-11-04

    Clinical studies have confirmed that indomethacin (Indo) can reduce the incidence and severity of post-endoscopicretrogradecholangio-pancreatography pancreatitis (PEP) effectively. However, the role of Indo on severe acute pancreatitis (SAP) is not clear. In the present study, we aimed to explore the effects of Indo treatment on SAP model induced by caerulein combined with lipopolysaccharide. After intraperitoneal injection of Indo in mice, both the severity of SAP and the serum levels of amylase, lipase, and proinflammatory cytokines were decreased. Furthermore, the mRNA and protein levels of NLRP3 inflammasome pathway (NLRP3,ASC and IL-1β) in pancreatic tissues were down-regulated. In vitro experiments, by isolating the pancreatic acinar cells (PACs) from mice, we found that Indo significantly reduced lactate dehydrogenase(LDH) excretion, increased the cell activity, and inhibited the NLRP3 inflammasome pathway of PACs. Taken together, our data showed that Indo could protect pancreatic acinar cell from injury by inhabiting NLRP3 pathway and decreased the severity of SAP accordingly. Copyright © 2017. Published by Elsevier Inc.

  13. Novel Metagenome-Derived, Cold-Adapted Alkaline Phospholipase with Superior Lipase Activity as an Intermediate between Phospholipase and Lipase

    PubMed Central

    Lee, Mi-Hwa; Oh, Ki-Hoon; Kang, Chul-Hyung; Kim, Ji-Hoon; Oh, Tae-Kwang; Ryu, Choong-Min

    2012-01-01

    A novel lipolytic enzyme was isolated from a metagenomic library obtained from tidal flat sediments on the Korean west coast. Its putative functional domain, designated MPlaG, showed the highest similarity to phospholipase A from Grimontia hollisae CIP 101886, though it was screened from an emulsified tricaprylin plate. Phylogenetic analysis showed that MPlaG is far from family I.6 lipases, including Staphylococcus hyicus lipase, a unique lipase which can hydrolyze phospholipids, and is more evolutionarily related to the bacterial phospholipase A1 family. The specific activities of MPlaG against olive oil and phosphatidylcholine were determined to be 2,957 ± 144 and 1,735 ± 147 U mg−1, respectively, which means that MPlaG is a lipid-preferred phospholipase. Among different synthetic esters, triglycerides, and phosphatidylcholine, purified MPlaG exhibited the highest activity toward p-nitrophenyl palmitate (C16), tributyrin (C4), and 1,2-dihexanoyl-phosphatidylcholine (C8). Finally, MPlaG was identified as a phospholipase A1 with lipase activity by cleavage of the sn-1 position of OPPC, interfacial activity, and triolein hydrolysis. These findings suggest that MPlaG is the first experimentally characterized phospholipase A1 with lipase activity obtained from a metagenomic library. Our study provides an opportunity to improve our insight into the evolution of lipases and phospholipases. PMID:22544255

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

    PubMed Central

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

    2010-01-01

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

  15. Somatostatin inhibits cholecystokinin-induced pancreatic protein secretion via cholinergic pathways.

    PubMed

    Brodish, R J; Kuvshinoff, B W; McFadden, D W; Fink, A S

    1995-05-01

    Although somatostatin is a potent inhibitor of pancreatic exocrine secretion in vivo, its mechanism of action remains unclear. The influence of extrapancreatic nerves and intrapancreatic cholinergic activity on somatostatin-induced inhibition of pancreatic exocrine secretion was studied in conscious dogs. Chronic pancreatic fistulae were created in six mongrel dogs, and a second group of six dogs also underwent complete pancreatic denervation. The pancreatic responses to graded doses of cholecystokinin (12.5-200 ng/kg/h) and bethanechol (57-916 micrograms/kg/h), both alone and during background infusion of somatostatin-14 (800 pm/kg/h), were determined in all dogs. The cholecystokinin dose-response with a somatostatin-14 background was then repeated with the addition of atropine (10 micrograms/kg/h). In both groups of animals, cholecystokinin elicited a dose-dependent increase in pancreatic protein secretion that was inhibited significantly by somatostatin-14. Regardless of the status of extrapancreatic nerves, atropine further inhibited cholecystokinin-induced protein secretion beyond that evoked by somatostatin-14. In both innervated and denervated animals, cholinergic stimulation with bethanechol elicited a dose-dependent increase in pancreatic protein secretion that was unaffected by somatostatin-14. We conclude that extrapancreatic nerves do not mediate the inhibitory effects of somatostatin-14. Somatostatin-14 appears to inhibit cholecystokinin-induced pancreatic secretion by an intrapancreatic cholinergic mechanism.

  16. Identification and sequence analyses of novel lipase encoding novel thermophillic bacilli isolated from Armenian geothermal springs.

    PubMed

    Shahinyan, Grigor; Margaryan, Armine; Panosyan, Hovik; Trchounian, Armen

    2017-05-02

    Among the huge diversity of thermophilic bacteria mainly bacilli have been reported as active thermostable lipase producers. Geothermal springs serve as the main source for isolation of thermostable lipase producing bacilli. Thermostable lipolytic enzymes, functioning in the harsh conditions, have promising applications in processing of organic chemicals, detergent formulation, synthesis of biosurfactants, pharmaceutical processing etc. In order to study the distribution of lipase-producing thermophilic bacilli and their specific lipase protein primary structures, three lipase producers from different genera were isolated from mesothermal (27.5-70 °C) springs distributed on the territory of Armenia and Nagorno Karabakh. Based on phenotypic characteristics and 16S rRNA gene sequencing the isolates were identified as Geobacillus sp., Bacillus licheniformis and Anoxibacillus flavithermus strains. The lipase genes of isolates were sequenced by using initially designed primer sets. Multiple alignments generated from primary structures of the lipase proteins and annotated lipase protein sequences, conserved regions analysis and amino acid composition have illustrated the similarity (98-99%) of the lipases with true lipases (family I) and GDSL esterase family (family II). A conserved sequence block that determines the thermostability has been identified in the multiple alignments of the lipase proteins. The results are spreading light on the lipase producing bacilli distribution in geothermal springs in Armenia and Nagorno Karabakh. Newly isolated bacilli strains could be prospective source for thermostable lipases and their genes.

  17. CMV allograft pancreatitis: diagnosis, treatment, and histological features.

    PubMed

    Klassen, D K; Drachenberg, C B; Papadimitriou, J C; Cangro, C B; Fink, J C; Bartlett, S T; Weir, M R

    2000-05-15

    Cytomegalovirus (CMV) infection is a common problem in solid organ transplant recipients. CMV infection of pancreas allografts is not, however, well described. We report the clinical presentation, histologic findings, treatment, and outcome in four patients with CMV allograft pancreatitis. These patients presented 18 weeks to 44 months after transplantation with elevated serum amylase and lipase and were suspected to have acute rejection. Percutaneous pancreas allograft biopsy specimens showed evidence of tissue invasive CMV infection. One patient had simultaneous CMV infection and acute rejection. Prolonged treatment with ganciclovir resulted in clinical and histologic resolution of the CMV disease. Rejection was successfully treated. Primary CMV infection in seronegative recipients seemed to be a risk factor. Three patients maintain normal allograft function; one patient lost function due to chronic rejection. The histology of tissue-invasive CMV pancreas allograft infection and its differentiation from acute rejection is described. Prompt diagnosis and prolonged therapy with antiviral agents can result in maintenance of allograft function.

  18. Secretion of pancreatic polypeptide in patients with pancreatic endocrine tumors.

    PubMed

    Adrian, T E; Uttenthal, L O; Williams, S J; Bloom, S R

    1986-07-31

    Pancreatic polypeptide is often secreted by pancreatic endocrine tumors and is considered a marker for such tumors. To investigate the diagnostic value of this marker, we studied 323 patients with proved pancreatic endocrine tumors. We found plasma concentrations of pancreatic polypeptide to be elevated (more than 300 pmol per liter) in 144 patients (diagnostic sensitivity, 45 percent). However, plasma levels of pancreatic polypeptide can also be elevated in the absence of a pancreatic tumor. To ascertain whether the administration of atropine could distinguish between normal and tumor-associated polypeptide secretion, we studied 30 patients with pancreatic tumors and high plasma levels of pancreatic polypeptide, 18 patients without tumors who had elevated levels of pancreatic polypeptide, and eight normal controls. Polypeptide levels in the 18 patients without tumors were substantially lower than in the 30 patients with tumors. Atropine (1 mg intramuscularly) did not suppress polypeptide levels in patients with tumors, but did suppress plasma levels by more than 50 percent in all subjects without tumors. Thus, although its diagnostic sensitivity is low, pancreatic polypeptide appears to be a useful adjunctive marker of many pancreatic endocrine tumors, and the atropine suppression test can be used to distinguish normal from tumor-related secretion of the polypeptide. Identification of the type of pancreatic endocrine tumor still requires measurement of the hormone that is specific for the tumor.

  19. General Information about Pancreatic Cancer

    MedlinePlus

    ... Research Pancreatic Cancer Treatment (PDQ®)–Patient Version General Information About Pancreatic Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  20. Pancreatic trauma: A concise review

    PubMed Central

    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. Candida in acute pancreatitis.

    PubMed

    Chakrabarti, Arunaloke; Rao, Pooja; Tarai, Bansidhar; Shivaprakash, Mandya Rudramurthy; Wig, Jaidev

    2007-01-01

    A Candida infection of the pancreas, which previously was considered extremely unusual, has been increasingly reported in recent years. The present study was conducted with the aim of performing a cohort analysis of our patients with acute pancreatitis to find out the incidence, sites, and species of Candida involvement; and to evaluate the risk factors, severity, and course of illness of such patients. A total of 335 patients with acute pancreatitis were investigated for a possible Candida infection of the pancreas from January 2000 to May 2003. The clinical records of all those patients who were positive for Candida spp. isolation from pancreatic tissue were analyzed. The clinical records of 32 more cases, randomly selected from the patients who were investigated for candidal pancreatitis but were negative for Candida spp., were also analyzed in order to compare their findings with those patients with a true Candida infection of the pancreas. A true or possible Candida infection was observed in 41 (12.2%) of those 335 patients and Candida tropicalis was the most common isolate (43.9%). Candida spp. were isolated from pancreatic necrotic tissue in 22 (6.6%) patients (true infection). A possible Candida infection (positive drain fluid effluents at least twice, without any Candida isolation from pre/per operative samples from pancreas) was seen in 19 (5.7%) patients. Candida was also isolated exclusively from the blood in another 19 patients with a clinical diagnosis of acute pancreatitis. A risk factor analysis showed that patients with severe injury to the pancreas, on prophylactic fluconazole, and after surgical intervention were significantly more prone to develop a Candida infection. Patients with a Candida superinfection also had a significantly increased hospital stay and higher mortality. This study thus emphasizes the important role of Candida infection in patients with acute pancreatitis and demonstrates the need for early attention.

  2. MIF Drives Pancreatic Cancer Aggressiveness by Downregulating NR3C2 | Center for Cancer Research

    Cancer.gov

    Pancreatic cancer, while relatively rare, is an aggressive disease ranked as the fourth leading cause of cancer-related death in the US. Because most patients are diagnosed at an advanced stage and their tumors resist available treatments, novel therapeutic targets are urgently needed. Macrophage Migration Inhibitory Factor (MIF) is a proinflammatory cytokine that is elevated

  3. Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis.

    PubMed

    Pendharkar, Sayali A; Drury, Marie; Walia, Monika; Korc, Murray; Petrov, Maxim S

    2017-08-01

    Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. GRP is significantly increased in patients with AGM after pancreatitis and is associated with increased levels of pro

  4. Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis

    PubMed Central

    Pendharkar, Sayali A.; Drury, Marie; Walia, Monika; Korc, Murray; Petrov, Maxim S.

    2017-01-01

    Background Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. Methods Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. Results A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. Conclusion GRP is significantly increased in patients with AGM after pancreatitis and is

  5. Antioxidant Effect of Ukrain Versus N-Acetylcysteine Against Acute Biliary Pancreatitis in An Experimental Rat Model.

    PubMed

    Zeren, Sezgin; Bayhan, Zulfu; Koçak, Cengiz; Koçak, Fatma Emel; Metineren, Mehmet Huseyin; Savran, Bircan; Kocak, Havva; Algin, Mustafa Cem; Kahraman, Cuneyt; Kocak, Ahmet; Cosgun, Suleyman

    2017-04-01

    Purpose/Aim: Oxidative stress plays an important role in the pathogenesis of acute pancreatitis (AP). We compared the therapeutic effects of Ukrain (NSC 631570) and N-acetylcysteine (NAC) in rats with AP. Forty male Sprague Dawley rats were divided into four groups: controls; AP; AP with NAC; and AP with Ukrain. AP was induced via the ligation of the bile-pancreatic duct; drugs were administered intraperitoneally (i.p.) 30 min and 12 h after AP induction. Twenty-four hours after AP induction, animals were sacrificed and the pancreas was excised. Levels of malondialdehyde (MDA) and nitric oxide (NO), and activity levels of tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO) were measured in tissue samples. Total oxidant status (TOS), total antioxidant status (TAS), and total bilirubin, as well as activity levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase and lipase were measured in serum samples. Pancreatic tissue histopathology was also evaluated. Test drugs reduced levels of MDA, NO, TNF-α, total bilirubin, AST, ALT, TOS and MPO, amylase and lipase activities (P < 0.001), and increased TAS (P < 0.001). Rats treated with test drugs attenuated AP-induced morphologic changes and decreased pancreatic damage scores compared with the AP group (P < 0.05). Both test drugs attenuated pancreatic damage, but the therapeutic effect was more pronounced in rats that received Ukrain than in those receiving NAC. These results suggest that treatment with Ukrain or NAC can reduce pancreatic damage via anti-inflammatory and antioxidant effects.

  6. Endoscopic Therapies for Chronic Pancreatitis.

    PubMed

    Adler, Jeffrey M; Gardner, Timothy B

    2017-07-01

    Chronic pancreatitis is a fibroinflammatory disease of the pancreas leading to varying degrees of endocrine and exocrine dysfunction. Treatment options are generally designed to control the pain of chronic pancreatitis, and endoscopic therapy is one of the main treatment modalities. Herein, we describe the endoscopic management of pancreatic duct calculi and strictures, entrapment of the intrapancreatic bile duct, celiac plexus interventions, and drainage of pancreatic pseudocysts.

  7. Hypocalcemia in acute pancreatitis revisited

    PubMed Central

    Ahmed, Armin; Azim, Afzal; Gurjar, Mohan; Baronia, Arvind Kumar

    2016-01-01

    Hypocalcemia is a frequent finding in acute pancreatitis. Severe hypocalcemia can present with neurological as well as cardiovascular manifestations. Correction of hypocalcemia by parenteral calcium infusion remains a controversial topic as intracellular calcium overload is the central mechanism of acinar cell injury in pancreatitis. The current article deals with the art and science of calcium correction in pancreatitis patients. PMID:27076730

  8. Pancreatic Cancer—Patient Version

    Cancer.gov

    Pancreatic cancer can form in exocrine cells and neuroendocrine cells. The exocrine type is more common and is usually found at an advanced stage. Pancreatic neuroendocrine tumors are less common but have a better prognosis. Start here to find information on pancreatic cancer treatment, research, and statistics.

  9. The management of pancreatic trauma.

    PubMed

    Khan, M A; Cameron, I

    2010-12-01

    Pancreatic trauma is an uncommon occurrence and so a consensus about optimal management is not readily available. Isolated pancreatic injury occurs only occasionally, as in the majority of cases there is concurrent visceral or vascular injury. Morbidity and mortality are related to delay in diagnosis, concurrent organ injury or the presence and extent of pancreatic duct injury.

  10. Models of inhibitory control

    PubMed Central

    Logan, Gordon D.

    2017-01-01

    We survey models of response inhibition having different degrees of mathematical, computational and neurobiological specificity and generality. The independent race model accounts for performance of the stop-signal or countermanding task in terms of a race between GO and STOP processes with stochastic finishing times. This model affords insights into neurophysiological mechanisms that are reviewed by other authors in this volume. The formal link between the abstract GO and STOP processes and instantiating neural processes is articulated through interactive race models consisting of stochastic accumulator GO and STOP units. This class of model provides quantitative accounts of countermanding performance and replicates the dynamics of neural activity producing that performance. The interactive race can be instantiated in a network of biophysically plausible spiking excitatory and inhibitory units. Other models seek to account for interactions between units in frontal cortex, basal ganglia and superior colliculus. The strengths, weaknesses and relationships of the different models will be considered. We will conclude with a brief survey of alternative modelling approaches and a summary of problems to be addressed including accounting for differences across effectors, species, individuals, task conditions and clinical deficits. This article is part of the themed issue ‘Movement suppression: brain mechanisms for stopping and stillness’. PMID:28242727

  11. Robotic transgastric cystgastrostomy and pancreatic debridement in the management of pancreatic fluid collections following acute pancreatitis.

    PubMed

    Kirks, Russell C; Sola, Richard; Iannitti, David A; Martinie, John B; Vrochides, Dionisios

    2016-01-01

    Pancreatic and peripancreatic fluid collections may develop after severe acute pancreatitis. Organized fluid collections such as pancreatic pseudocyst and walled-off pancreatic necrosis (WOPN) that mature over time may require intervention to treat obstructive or constitutional symptoms related to the size and location of the collection as well as possible infection. Endoscopic, open surgical and minimally invasive techniques are described to treat post-inflammatory pancreatic fluid collections. Surgical intervention may be required to treat collections containing necrotic pancreatic parenchyma or in locations not immediately apposed to the stomach or duodenum. Comprising a blend of the surgical approach and the clinical benefits of minimally invasive surgery, the robot-assisted technique of pancreatic cystgastrostomy with pancreatic debridement is described.

  12. Estolides Synthesis Catalyzed by Immobilized Lipases

    PubMed Central

    Aguieiras, Erika C. G.; Veloso, Cláudia O.; Bevilaqua, Juliana V.; Rosas, Danielle O.; da Silva, Mônica A. P.; Langone, Marta A. P.

    2011-01-01

    Estolides are vegetable-oil-based lubricants obtained from oleic acid or any source of hydroxy fatty acids. In this work, the estolides synthesis from oleic acid and methyl ricinoleate (biodiesel from castor oil), using immobilized commercial lipases (Novozym 435, Lipozyme RM-IM, and Lipozyme TL-IM) in a solvent-free medium was investigated. Acid value was used to monitor the reaction progress by determining the consumption of acid present in the medium. Novozym 435 showed the best performance. Water removal improved the conversion. Novozym 435 was more active at atmospheric pressure. Novozym 435 was reused four times with conversion reaching 15% after the fourth reaction at 80°C. Estolides produced under the reaction conditions used in this work presented good properties, such as, low temperature properties as pour point (−24°C), viscosity (23.9 cSt at 40°C and 5.2 cSt at 100°C), and viscosity index (153). PMID:21755040

  13. Monoacylglycerol lipase promotes metastases in nasopharyngeal carcinoma.

    PubMed

    Hu, Wen-Rong; Lian, Yi-Fan; Peng, Li-Xia; Lei, Jin-Ju; Deng, Cheng-Cheng; Xu, Miao; Feng, Qi-Sheng; Chen, Li-Zhen; Bei, Jin-Xin; Zeng, Yi-Xin

    2014-01-01

    Monoacylglycerol lipase (MAGL) is a serine hydrolase that hydrolyzes monoacylglycerides into free fatty acids and glycerol. It has recently been found to be involved in cancer progression through the free fatty acid or endocannabinoid network after studies on its function in the endocannabinoid system. Here, we determined a role for MAGL in nasopharyngeal carcinoma (NPC), which is known for its high metastatic potential. Among the different NPC cells we tested, MAGL was highly expressed in high metastatic NPC cells, whereas low metastatic potential NPC cells exhibited lower expression of MAGL. Overexpression of MAGL in low metastatic NPC cells enhanced their motile behavior and metastatic capacity in vivo. Conversely, knockdown of MAGL reduced the motility of highly metastatic cells, reducing their metastatic capacity in vivo. Growth rate was not influenced by MAGL in either high or low metastatic cells. MAGL expression was associated with the epithelial-mesenchymal transition (EMT) proteins, such as E-cadherin, vimentin and Snail. It was also related to the sidepopulation (SP) of NPC cells. Our findings establish that MAGL promotes metastases in NPC through EMT, and it may serve as a target for the prevention of NPC metastases.

  14. Summary and recommendations from the Australasian guidelines for the management of pancreatic exocrine insufficiency.

    PubMed

    Smith, Ross C; Smith, Sarah F; Wilson, Jeremy; Pearce, Callum; Wray, Nick; Vo, Ruth; Chen, John; Ooi, Chee Y; Oliver, Mark; Katz, Tamarah; Turner, Richard; Nikfarjam, Mehrdad; Rayner, Christopher; Horowitz, Michael; Holtmann, Gerald; Talley, Nick; Windsor, John; Pirola, Ron; Neale, Rachel

    2016-01-01

    Because of increasing awareness of variations in the use of pancreatic exocrine replacement therapy, the Australasian Pancreatic Club decided it was timely to re-review the literature and create new Australasian guidelines for the management of pancreatic exocrine insufficiency (PEI). A working party of expert clinicians was convened and initially determined that by dividing the types of presentation into three categories for the likelihood of PEI (definite, possible and unlikely) they were able to consider the difficulties of diagnosing PEI and relate these to the value of treatment for each diagnostic category. Recent studies confirm that patients with chronic pancreatitis receive similar benefit from pancreatic exocrine replacement therapy (PERT) to that established in children with cystic fibrosis. Severe acute pancreatitis is frequently followed by PEI and PERT should be considered for these patients because of their nutritional requirements. Evidence is also becoming stronger for the benefits of PERT in patients with unresectable pancreatic cancer. However there is as yet no clear guide to help identify those patients in the 'unlikely' PEI group who would benefit from PERT. For example, patients with coeliac disease, diabetes mellitus, irritable bowel syndrome and weight loss in the elderly may occasionally be given a trial of PERT, but determining its effectiveness will be difficult. The starting dose of PERT should be from 25,000-40,000 IU lipase taken with food. This may need to be titrated up and there may be a need for proton pump inhibitors in some patients to improve efficacy. Copyright © 2016 IAP and EPC. Published by Elsevier India Pvt Ltd. All rights reserved.

  15. Fasting upregulates adipose triglyceride lipase and hormone-sensitive lipase levels and phosphorylation in mouse kidney.

    PubMed

    Marvyn, Phillip M; Bradley, Ryan M; Button, Emily B; Mardian, Emily B; Duncan, Robin E

    2015-06-01

    Circulating non-esterified fatty acids (NEFA) rise during fasting and are taken up by the kidneys, either directly from the plasma or during re-uptake of albumin from glomerular filtrate, and are stored as triacylglycerol (TAG). Subsequent utilization of stored fatty acids requires their hydrolytic release from cellular lipid droplets, but relatively little is known about renal lipolysis. We found that total [(3)H]triolein hydrolase activity of kidney lysates was significantly increased by 15% in the fasted state. Adipose triglyceride lipase (Atgl) and hormone-sensitive lipase (Hsl) mRNA expression was time-dependently increased by fasting, along with other fatty acid metabolism genes (Pparα, Cd36, and Aox). ATGL and HSL protein levels were also significantly induced (by 239 ± 7% and 322 ± 8%, respectively). Concomitant with changes in total protein levels, there was an increase in ATGL phosphorylation at the AMPK-regulated serine 406 site in the 14-3-3 binding motif, and an increase in HSL phosphorylation at serines 565 and 660 that are regulated by AMPK and PKA, respectively. Using immunofluorescence, we further demonstrate nearly ubiquitous expression of ATGL in the renal cortex with a concentration on the apical/lumenal surface of some cortical tubules. Our findings suggest a role for ATGL and HSL in kidney lipolysis.

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

    PubMed Central

    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

  17. Pancreatitis induced by pegylated interferon alfa-2b in a patient affected by chronic hepatitis C.

    PubMed

    Cecchi, Enrica; Forte, Paolo; Cini, Elisabetta; Banchelli, Grazia; Ferlito, Chiara; Mugelli, Alessandro

    2004-01-01

    A middle-aged man was admitted to the ED because of nausea and vomiting, abdominal distention and fainting. A blood analysis revealed high levels of serum amylase and lipase, confirming a diagnosis of acute pancreatitis. The history showed that the patient had self-administered a single dose of pegylated interferon alfa-2b and ribavirin daily for 7 days for chronic hepatitis C. The medications were stopped and his condition gradually improved. In agreement with the literature and the Naranjo algorythm result, pegylated interferon alfa-2b is associated with acute pancreatitis. Identification of a few signs and symptoms is the first 'signal' in preventing a serious drug-induced adverse event.

  18. [Duodenal and pancreatic injuries].

    PubMed

    De Angelis, P; Bergaminelli, C; Pastore, S; Giardiello, C; Salzano, A; Vecchio, G

    2000-04-01

    Pancreatic and duodenal injuries occur rather infrequently and the incidence ranges between 1% and 12% of all abdominal injuries. The high rate of mortality and morbidity (10-40%) depends on associated complication rate of all intra-abdominal organs (90%). Twenty-five cases of pancreatic and duodenal injuries observed between 1987 and 1997, with an incidence of 0.7% of all abdominal injuries, are reported. In 16 cases the cause was penetrating injury (gunshot) and in 9 cases it was blunt abdominal trauma. Only two patients presented an isolated pancreatic lesion, all the others had at least an associated lesion. In all the cases the patients were male and they were submitted to emergency laparotomy. The mortality rate was 20%, the morbidity was 24%. The relatively low incidence of these injuries and the high rate of associated lesions cause a difficult diagnostic and therapeutic approach, the absence of a unified method to follow and the unsatisfactory results observed.

  19. High cell density fed-batch fermentations for lipase production: feeding strategies and oxygen transfer.

    PubMed

    Salehmin, M N I; Annuar, M S M; Chisti, Y

    2013-11-01

    This review is focused on the production of microbial lipases by high cell density fermentation. Lipases are among the most widely used of the enzyme catalysts. Although lipases are produced by animals and plants, industrial lipases are sourced almost exclusively from microorganisms. Many of the commercial lipases are produced using recombinant species. Microbial lipases are mostly produced by batch and fed-batch fermentation. Lipases are generally secreted by the cell into the extracellular environment. Thus, a crude preparation of lipases can be obtained by removing the microbial cells from the fermentation broth. This crude cell-free broth may be further concentrated and used as is, or lipases may be purified from it to various levels. For many large volume applications, lipases must be produced at extremely low cost. High cell density fermentation is a promising method for low-cost production: it allows a high concentration of the biomass and the enzyme to be attained rapidly and this eases the downstream recovery of the enzyme. High density fermentation enhances enzyme productivity compared with the traditional submerged culture batch fermentation. In production of enzymes, a high cell density is generally achieved through fed-batch operation, not through perfusion culture which is cumbersome. The feeding strategies used in fed-batch fermentations for producing lipases and the implications of these strategies are discussed. Most lipase-producing microbial fermentations require oxygen. Oxygen transfer in such fermentations is discussed.

  20. Influence of cosolvents on the hydrophobic surface immobilization topography of Candida antarctica lipase B

    USDA-ARS?s Scientific Manuscript database

    The presence of cosolvents and co-solutes during the immobilization of lipases on hydrophobic supports may influence the extent of lipase immobilization and the long-term catalytic stability of the biocatalyst. Candida antarctica B lipase immobilization was examined on a hydrophobic surface, i.e., ...

  1. A novel frameshift mutation in the lipoprotein lipase gene is rescued by alternative messenger RNA splicing.

    PubMed

    Laurie, Andrew D; Kyle, Campbell V

    Type I hyperlipoproteinemia, manifesting as chylomicronemia and severe hypertriglyceridemia, is a rare autosomal recessive disorder usually caused by mutations in the lipoprotein lipase gene (LPL). We sought to determine whether mutations in LPL could explain the clinical indications of a patient presenting with pancreatitis and hypertriglyceridemia. Coding regions of LPL were amplified by polymerase chain reaction and analyzed by nucleotide sequencing. The LPL messenger RNA transcript was also analyzed to investigate whether alternative splicing was occurring. The patient was homozygous for the mutation c.767_768insTAAATATT in exon 5 of the LPL gene. This mutation is predicted to result in either a truncated nonfunctional LPL, or alternatively a new 5' donor splice site may be used, resulting in a full-length LPL with an in-frame deletion of 3 amino acids. Analysis of messenger RNA from the patient showed that the new splice site is used in vivo. Homozygosity for a mutation in the LPL gene was consistent with the clinical findings. Use of the new splice site created by the insertion mutation rescues an otherwise damaging frameshift mutation, resulting in expression of an almost full-length LPL that is predicted to be partially functional. The patient therefore has a less severe form of type I hyperlipoproteinemia than would be expected if she lacked any functional LPL. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  2. Gel filtration applied to the study of lipases and other esterases

    PubMed Central

    Downey, W. K.; Andrews, P.

    1965-01-01

    1. Sephadex G-100 and G-200 gel-filtration columns were calibrated for molecular-weight estimation with proteins of known molecular weights, and used to study the composition of several lipase or esterase preparations. 2. Enzymes from cow's milk, rat adipose tissue and pig pancreas were detected in the column effluents by their ability to liberate free acid from emulsified tributyrin at pH 8·5. 3. Four tributyrinases were detected in preparations from individual cow's milks. Molecular weights 62000, 75000 and 112000 were estimated for three of them, but although the fourth may be of unusually low molecular weight an estimate was not possible. 4. Extracts of rat adipose tissue apparently contained six tributyrinases (molecular weights 39000, 47000, 55000, 68000, 75000 and 200000) but the relative amounts of these enzymes varied widely from rat to rat. 5. Tributyrinase activity in juice expressed from pig pancreatic tissue was due mainly to one enzyme (molecular weight 42000). On the other hand, activity in extracts of acetone-dried pancreas was confined to material of molecular weight > 106, which may be an aggregated form of the lower-molecular-weight enzyme. 6. Activity in fractionated wheat-germ extracts was assayed with emulsified triacetin substrate, and was evidently due to one enzyme (molecular weight 51000). 7. Some problems arising in the application of gel filtration to the study of lipase–esterase systems were indicated. PMID:14340054

  3. Improving adsorption and activation of the lipase immobilized in amino-functionalized ordered mesoporous SBA-15

    NASA Astrophysics Data System (ADS)

    Xu, Yun-qiang; Zhou, Guo-wei; Wu, Cui-cui; Li, Tian-duo; Song, Hong-bin

    2011-05-01

    Ordered mesoporous SBA-15 was prepared by hydrothermal process and was functionalized with(3-aminopropyl) triethoxysilane (APTES) by post-synthesis-grafting method. The materials were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive spectrometer (EDS), small-angle X-ray powder diffraction (SAXRD), N 2 adsorption-desorption and Fourier transform infrared spectroscopy (FT-IR). The results indicated that SBA-15 had a 2-dimensional hexagonal p6 mm mesoscopic structure and the mesoscopic structure was remained after the functionalization procedure. The activities of porcine pancreatic lipase (PPL) immobilized in SBA-15 by physical adsorption and in APTES functionalized SBA-15 by chemical adsorption were studied by hydrolysis of triacetin. Chemically adsorbed PPL showed higher loading amount and catalytic activity comparing with physically adsorbed PPL. The stability of immobilized PPL against thermal and pH of reaction medium was significantly improved. Recycling experiments showed that chemically adsorbed PPL exhibited better reusability than physically adsorbed PPL.

  4. Hypertriglyceridaemia-induced pancreatitis

    PubMed Central

    Weston, Natasha; Fernando, Upul; Baskar, Varadarajan

    2013-01-01

    Hypertriglyceridaemia is the third most common cause of acute pancreatitis but is relatively rare and therefore requires a high level of clinical suspicion to be diagnosed. We discuss the case of a 46-year-old man who initially presented to the accident and emergency department with suspected first presentation of diabetic ketoacidosis (DKA) and a normal amylase but who did not respond to DKA treatment. Further history revealed significant cardiovascular risk factors, examination showed an evidence of hyperlipidaemia and investigations revealed acute pancreatitis secondary to hypertriglyceridaemia. We discuss the causes of hypertriglyceridaemia, the difficulty in differentiating primary versus secondary hypertriglyceridaemia, possible pathogenesis and current evidence-based treatments. PMID:23446049

  5. Pathophysiology of chronic pancreatitis.

    PubMed

    Behrman, Stephen W; Fowler, Eric S

    2007-12-01

    Although the most common causes of chronic pancreatitis have not changed, it has become clear that a host of modifying biochemical, inflammatory, neural, and genetic deviations allows the disease to progress. Alterations in biochemical composition allow calcific stone formation, whereas various toxins, cytokines, and neuropeptides contribute to the progression of fibrosis and pain production. The basic cellular structure contributing to fibrosis of the pancreas has been elucidated and factors responsible for its activation delineated. Of most importance is the recent recognition of a set of genetic mutations that results in several aberrations of normal pancreatic physiology, which, in conjunction with other inciting insults or by themselves, allow the disease to begin and progress.

  6. Pancreatic and Intestinal Function Post Roux-en-Y Gastric Bypass Surgery for Obesity

    PubMed Central

    O’Keefe, Stephen J D; Rakitt, Tina; Ou, Junhai; El Hajj, Ihab I; Blaney, Elizabeth; Vipperla, Kishore; Holst, Jens-Jules; Rehlfeld, Jens

    2017-01-01

    Objectives: Despite the fact that the most effective treatment for morbid obesity today is gastric bypass surgery, some patients develop life-threatening nutritional complications associated with their weight loss. Methods: Here we examine the influence of the altered anatomy and digestive physiology on pancreatic secretion and fat absorption. Thirteen post Roux-en-Y gastric bypass (RYGB) patients who had lost >100 lbs in the first year following surgery and who gave variable histories of gastrointestinal (GI) dysfunction, were selected for study. Food-stimulated pancreatic enzyme secretion and GI hormone responses were measured during 2 h perfusions of the Roux limb with a standard polymeric liquid formula diet and polyethylene glycol marker, with collections of secretions from the common channel distal to the anastomosis and blood testing. Fat absorption was then measured during a 72 h balance study when a normal diet was given containing ~100 g fat/d. Results: Result showed that all patients had some fat malabsorption, but eight had coefficients of fat absorption <80%, indicative of steatorrhea. This was associated with significantly lower feed-stimulated secretion rates of trypsin, amylase, and lipase, and higher plasma peptide-YY concentrations compared with healthy controls. Five steatorrhea patients were subsequently treated with low quantities of pancreatic enzyme supplements for 3 months, and then retested. The supplements were well tolerated, and fat absorption improved in four of five patients accompanied by an increase in lipase secretion, but body weight increased in only three. Postprandial breath hydrogen concentrations were elevated with some improvement following enzyme supplementation suggesting persistent bacterial overgrowth and decreased colonic fermentation. Conclusions: Our investigations revealed a wide spectrum of gastrointestinal abnormalities, including fat malabsorption, impaired food stimulated pancreatic secretion, ileal brake

  7. Lipases as catalysts in synthesis of fine chemicals.

    PubMed

    Baldessari, Alicia

    2012-01-01

    The application of lipases as catalysts in the synthesis of an intermediate of alfuzosin and lapyrium chloride is described. In the first case, the one-pot procedure to obtain the intermediate involves the treatment of tetrahydrofuroic acid with ethanol in the presence of Candida antarctica lipase followed by the addition of N-methyl-1,3-diaminopropane. In the second part of the chapter, an efficient route for large-scale preparation of lapyrium chloride is developed from chloroacetic acid in four steps, three of them enzymatic. Due to the chemoselective behavior of the lipases, both products described in the present chapter were obtained in a high degree of purity and yield, applying mild reaction conditions, and following a low environmental impact methodology.

  8. The immobilization of lipase on PVDF-co-HFP membrane

    NASA Astrophysics Data System (ADS)

    Kayhan, Naciye; Eyüpoǧlu, Volkan; Adem, Şevki

    2016-04-01

    Lipase is an enzyme having a lot of different industrial applications such as biodiesel production, biopolymer synthesis, enantiopure pharmaceutical productions, agrochemicals, etc. Its immobilized form on different substances is more conventional and useful than its free form. Supporting material was prepared using PVDF-co-HFP in laboratory conditions and attached 1,4-diaminobutane (DA) and epichlorohydrin (EPI) ligands to the membrane to immobilize lipase enzyme. The immobilization conditions such as enzyme amount, pH, the concentration of salt, thermal stability and activity were stabilized for our experimental setup. Then, biochemical characterizations were performed on immobilized lipase PVDF-co-HFP regarding optimal pH activity, temperature and thermal stability. Also, the desorption ratios of immobilized enzyme in two different pathway were investigated to confirm immobilization stability for 24 hours.

  9. Chemo-enzymatic synthesis of vinyl and l-ascorbyl phenolates and their inhibitory effects on advanced glycation end products.

    PubMed

    Hwang, Seung Hwan; Wang, Zhiqiang; Lim, Soon Sung

    2017-01-01

    This study successfully established the feasibility of a two-step chemo-enzymatic synthesis of l-ascorbyl phenolates. Intermediate vinyl phenolates were first chemically produced and then underwent trans-esterification with l-ascorbic acid in the presence of Novozyme 435® (Candida Antarctica lipase B) as a catalyst. Twenty vinyl phenolates and 11 ascorbyl phenolates were subjected to in vitro bioassays to investigate their inhibitory activity against advanced glycation end products (AGEs). Among them, vinyl 4-hydroxycinnamate (17VP), vinyl 4-hydroxy-3-methoxycinnamate (18VP), vinyl 4-hydroxy-3,5-dimethoxycinnamate (20VP), ascorbyl 4-hydroxy-3-methoxycinnamate (18AP) and ascorbyl 3,4-dimethoxycinnamate (19AP) showed 2-10 times stronger inhibitory activities than positive control (aminoguanidine and its precursors). These results indicated that chemo-enzymatically synthesized compounds have AGE inhibitory effect and thus are effective in either preventing or retarding glycation protein formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. [Pancreatic serous cystadenoma associated with pancreatic heterotopia].

    PubMed

    Mohamed, Hedfi; Dorra, Belghachem; Hela, Bouhafa; Cherif, Abdelhedi; Azza, Sridi; Karim, Sassi; Khadija, Bellil; Adnen, Chouchene

    2016-01-01

    Pancreatic heterotopias (HP) are rare. They can occur at any age with a slight male predominance. These lesions are usually asymptomatic and they are often found incidentally during upper or lower GI endoscopy or during the anatomo-pathological examination of an organ which was resected for other reasons; they can be isolated or associated with a digestive pathology. We report, through observation, the association of HP with serous cystadenoma of the pancreas discovered during examinations to identify the etiology of isolated abdominal pain. The aim of this study is to analyse clinical and histological features of this rare pathology.

  11. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21(st) century.

    PubMed

    Trang, Tony; Chan, Johanna; Graham, David Y

    2014-09-07

    Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.

  12. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21st century

    PubMed Central

    Trang, Tony; Chan, Johanna; Graham, David Y

    2014-01-01

    Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy. PMID:25206255

  13. Bioaccessibility and inhibitory effects on digestive enzymes of carnosic acid in sage and rosemary.

    PubMed

    Ercan, Pınar; El, Sedef Nehir

    2018-04-28

    In this study, the aim was to determine the bioaccessibilities of carnosic acid in sage and rosemary and in vitro inhibitory effects of these samples on lipid and starch digestive enzymes by evaluating the lipase, α-amylase and α-glucosidase enzyme inhibition activities. The content of carnosic acid in rosemary (18.72 ± 0.33 mg/g) was found to be higher than that content of that in sage (3.76 ± 0.13 mg/g) (p < 0.05). The carnosic acid bioaccessibilities were found as 45.10 ± 1.88% and 38.32 ± 0.21% in sage and rosemary, respectively. The tested sage and rosemary showed inhibitory activity against α-glucosidase (Concentration of inhibitor required to produce a 50% inhibition of the initial rate of reaction - IC 50 88.49 ± 2.35, 76.80 ± 1.68 μg/mL, respectively), α-amylase (IC 50 107.65 ± 12.64, 95.65 ± 2.73 μg/mL, respectively) and lipase (IC 50 6.20 ± 0.63, 4.31 ± 0.62 μg/mL, respectively). Furthermore, to the best of our knowledge, this is the first work that carnosic acid standard equivalent inhibition capacities (CAEIC 50 ) for these food samples were determined and these values were in agreement with the IC 50 values. These results show that sage and rosemary are potent inhibitors of lipase, α-amylase and α-glucosidase digestive enzymes. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Clinical Features of Lysosomal Acid Lipase Deficiency.

    PubMed

    Burton, Barbara K; Deegan, Patrick B; Enns, Gregory M; Guardamagna, Ornella; Horslen, Simon; Hovingh, Gerard K; Lobritto, Steve J; Malinova, Vera; McLin, Valerie A; Raiman, Julian; Di Rocco, Maja; Santra, Saikat; Sharma, Reena; Sykut-Cegielska, Jolanta; Whitley, Chester B; Eckert, Stephen; Valayannopoulos, Vassili; Quinn, Anthony G

    2015-12-01

    The aim of this study was to characterize key clinical manifestations of lysosomal acid lipase deficiency (LAL D) in children and adults. Investigators reviewed medical records of LAL D patients ages ≥5 years, extracted historical data, and obtained prospective laboratory and imaging data on living patients to develop a longitudinal dataset. A total of 49 patients were enrolled; 48 had confirmed LAL D. Mean age at first disease-related abnormality was 9.0 years (range 0-42); mean age at diagnosis was 15.2 years (range 1-46). Twenty-nine (60%) were male patients, and 27 (56%) were <20 years of age at the time of consent/assent. Serum transaminases were elevated in most patients with 458 of 499 (92%) of alanine aminotransferase values and 265 of 448 (59%) of aspartate aminotransferase values above the upper limit of normal. Most patients had elevated low-density lipoprotein (64% patients) and total cholesterol (63%) at baseline despite most being on lipid-lowering therapies, and 44% had high-density lipoprotein levels below the lower limit of normal. More than half of the patients with liver biopsies (n = 31, mean age 13 years) had documented evidence of steatosis (87%) and/or fibrosis (52%). Imaging assessments revealed that the median liver volume was ∼1.15 multiples of normal (MN) and median spleen volume was ∼2.2 MN. Six (13%) patients had undergone a liver transplant (ages 9-43.5 years). This study provides the largest longitudinal case review of patients with LAL D and confirms that LAL D is predominantly a pediatric disease causing early and progressive hepatic dysfunction associated with dyslipidemia that often leads to liver failure and transplantation.

  15. Therapeutic potential of monoacylglycerol lipase inhibitors.

    PubMed

    Mulvihill, Melinda M; Nomura, Daniel K

    2013-03-19

    Marijuana and aspirin have been used for millennia to treat a wide range of maladies including pain and inflammation. Both cannabinoids, like marijuana, that exert anti-inflammatory action through stimulating cannabinoid receptors, and cyclooxygenase (COX) inhibitors, like aspirin, that suppress pro-inflammatory eicosanoid production have shown beneficial outcomes in mouse models of neurodegenerative diseases and cancer. Both cannabinoids and COX inhibitors, however, have untoward effects that discourage their chronic usage, including cognitive deficits and gastrointestinal toxicity, respectively. Recent studies have uncovered that the serine hydrolase monoacylglycerol lipase (MAGL) links the endocannabinoid and eicosanoid systems together through hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) to provide the major arachidonic acid (AA) precursor pools for pro-inflammatory eicosanoid synthesis in specific tissues. Studies in recent years have shown that MAGL inhibitors elicit anti-nociceptive, anxiolytic, and anti-emetic responses and attenuate precipitated withdrawal symptoms in addiction paradigms through enhancing endocannabinoid signaling. MAGL inhibitors have also been shown to exert anti-inflammatory action in the brain and protect against neurodegeneration through lowering eicosanoid production. In cancer, MAGL inhibitors have been shown to have anti-cancer properties not only through modulating the endocannabinoid-eicosanoid network, but also by controlling fatty acid release for the synthesis of protumorigenic signaling lipids. Thus, MAGL serves as a critical node in simultaneously coordinating multiple lipid signaling pathways in both physiological and disease contexts. This review will discuss the diverse (patho)physiological roles of MAGL and the therapeutic potential of MAGL inhibitors in treating a vast array of complex human diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Sodium chloride effects on lipase activity in germinating rape seeds.

    PubMed

    Ben Miled, D D; Zarrouk, M; Chérif, A

    2000-12-01

    Seeds of rape (Brassica napus L.) were germinated at various NaCl concentrations up to 200 mM. Germinating levels, seedling growth, triacylglycerol mobilization and lipase activity were investigated. High salt concentrations resulted in retardation of seed germination. Seedling growth as measured by radicle length was severely reduced by NaCl doses higher than 50 mM. Moreover, the mobilization of storage oil in control rapeseed seedlings, started about 24 h after imbibition. As for germination and growth, elevated salt concentrations are found to delay triacylglycerol degradation. Experiments using triolein as substrate indicated clearly that lipase activity was inhibited by salt treatment.

  17. Environmental risk factors for chronic pancreatitis and pancreatic cancer.

    PubMed

    Nitsche, Claudia; Simon, Peter; Weiss, F Ulrich; Fluhr, Gabriele; Weber, Eckhard; Gärtner, Simone; Behn, Claas O; Kraft, Matthias; Ringel, Jörg; Aghdassi, Ali; Mayerle, Julia; Lerch, Markus M

    2011-01-01

    Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pa