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Experimental evidence of obesity as a risk factor for severe acute pancreatitis

World Journal of Gastroenterology 2009年第42期15卷 5260-5265页

作者： Jean-Louis Frossard Pierre Lescuyer Catherine m pastor Service of Gastroenterology Geneva University HospitalsGeneva 1205Switzerland Laboratory of pathophysiology and molecular imaging Geneva University HospitalsGeneva 1205Switzerland Service of Genetics and Central Laboratory Geneva University HospitalsGeneva 1205Switzerland

The incidence of acute pancreatitis, an inflammation of the pancreas, is increasing worldwide. Pancreatic injury is mild in 80%-90% of patients who recover without complications. The remaining patients may develop a severe disease with local complications such as acinar cell necrosis, abscess and remote organ injury including lung injury. The early prediction of the severity of the disease is an important goal for physicians in management of patients with acute pancreatitis in order to optimize the therapy and to prevent organ dysfunction and local complications. For that purpose, multiple clinical scale scores have been applied to patients with acute pancreatitis. Recently, a new problem has emerged： the increased severity of the disease in obese patients. However, the mechanisms by which obesity increases the severity of acute pancreatitis are unclear. Several hypotheses have been suggested：（1） obese patients have an increased inflammation within the pancreas; （2） obese patients have an increased accumulation of fat within and around the pancreas where necrosis is often located; （3） increase in both peri- and intra-pancreatic fat and inflammatory cells explain the high incidence of pancreatic inflammation and necrosis in obese patients; （4） hepatic dysfunction associated with obesity might enhance the systemic inflammatory response by altering the detoxiflcation of inflammatory mediators; and （5） ventilation/perfusion mismatch leading to hypoxia associated with a low pancreatic flow might reduce the pancreatic oxygenation and further enhance pancreatic injury. Recent experimental investigations also show an increased mortality and morbidity in obese rodents with acute pancreatitis and the implication of the adipokines leptin and adiponectin. Such models are important to investigate whether the inflammatory response of the disease is enhanced by obesity. It is exciting to speculate that manipulation of the adipokine milieu has the potential to influence the severi

关键词： Acute pancreatitis Obesity Adiponectin Leptin

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FRACTIONAL-STEP FINITE ELEmENT mETHOD FOR CALCULATION OF 3-D FREE SURFACE PROBLEm USING LEVEL SET mETHOD

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Journal of Hydrodynamics 2006年第6期18卷 742-747页

作者： ZHAO Lan-hao LI Tong-chun WANG Ling HERREROS m. I. pastor m. College of Water Conservancy and Hydropower Engineering Hohai University Naniing 210098 China Anhui Survey and Design Institute of Water Conservancy and Hydropower Hefei 230022 China CEDEX and E.T.S. de Caminos Madrid Spain

A two-step Taylor-Galerkin fractional-step finite element method, which is of second order accuracy in space and time, was proposed for the three-dimensional free surface problem. With this method, the intermediate velocity was explicitly obtained by neglecting pressure gradient term, and then the velocity was corrected by adding the effects of pressure once the pressure field had been obtained from the pressure Poisson equation. The level set approach was applied to track implicitly the free surface. In order to track the free surface, the transport equation of the level set function was solved at each time step and the level set function is reinitialized through iteration to maintain it as a distance function. The governing equations of the system were discretized by the two- step Taylor-Galerkin method, which is of high-order accuracy and easy to be used. The validity and reliability of this method in this article were proved by two numerical examples.

关键词： level set free surface two steps Taylor-Galerkin fractional step FEm

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Endothelial nitric oxide synthase regulation is altered in pancreas from cirrhotic rats

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World Journal of Gastroenterology 2006年第2期12卷 228-233页

作者： Jean-Louis Frossard Rafael Quadri Antoine Hadengue Philippe morel Catherine m pastor Division de Gastroenterologie Hpitaux Universitaires de Geneve Departement de Chirurgie Hopitaux Universitaires de Geneve Laboratoire de Physiopathologie Hepatique et Imagerie moleculaire Hpitaux Universitaires de Geneve

AIm： To determine whether biliary cirrhosis could induce pancreatic dysfunction such as modifications in endothelial nitric oxide synthase（eNOS） expression and whether the regulation of eNOS could be altered by the regulatory proteins caveolin and heat shock protein 90 （Hsp90）, as well as by the modifications of calmodulin binding to eNOS. mETHODS： Immunoprecipitations and Western blotting analysis were performed in pancreas isolated from sham and cirrhotic rats. RESULTS： Pancreatic injury was minor in cirrhotic rats but eNOS expression importantly decreased with the length （and the severity） of the disease. Because coimmunoprecipitation of eNOS with both Hsp90 and caveolin similarly decreased in cirrhotic rats, eNOS activity was not modified by this mechanism. In contrast, drrhosis decreased the calmodulin binding to eNOS with a concomitant decrease in eNOS activity. CONCLUSION： In biliary cirrhosis, pancreatic injury is minor but the pancreatic nitric oxide （NO） production is significantly decreased by two mechanisms： a decreased expression of the enzyme and a decreased binding of calmodulin to eNOS.

关键词： Pancreas Biliary cirrhosis Endothelial NO synthase Caveolin Heat shock protein 90

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Neutrophil depletion-but not prevention of Kupffer cell activation-decreases the severity of cerulein-induced acute pancreatitis

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World Journal of Gastroenterology 2006年第8期12卷 1219-1224页

作者： Catherine m pastor Alain Vonlaufen Fabianna Georgi Antoine Hadengue Philippe morel Jean-Louis Frossard Laboratoire de Physiopathologie Hépatique et Imagerie moléculaire H■pitaux Universitaires de GenèveB■timent CRoom 6-79524 Rue Micheli-du-Crest1205 GenevaSwitzerland Division of Gastroentérologie et Hépatologie H■pitaux Universitaires de Genève24 Rue Micheli-du-Crest1205 GenevaSwitzerland Département APSI H■pitaux Universitaires de Genève24 Rue Micheli-du-Crest1205 GenevaSwitzerland Département de Chirurgie H■pitaux Universitaires de Genève24 Rue Micheli-du-Crest1205 GenevaSwitzerland

AIm： To determine whether neutrophil depletion and Kupffer cell inhibition might combine their protective effects to decrease the severity of acute pancreatitis. mETHODS： Nice had cerulein administration to induce acute pancreatitis and were pretreated with either anti-mouse neutrophil serum or gadolinium chloride （GdCh） to prevent Kupffer cell activation, or both treatments. Injury was assessed in pancreas and lungs. myeloperoxidases （mPO） assessed neutrophil infiltration. Interleukin-6 （IL-6） and IL-10 were measured in serum, pancreas, lungs and liver. RESULTS： In mice with acute pancreatitis, neutrophil depletion reduced the severity of pancreatitis and pancreatitis-associated lung injury. Kupffer cell inactivation by GdCh had less protective effect, although IL-6 and IL-10 concentrations were significantly decreased. The protective treatment brought by neutrophil depletion was not enhanced by Kupffer cell inactivation and both treatments did not combine their protective effects. CONCLUSION： Our results confirm the role of activated neutrophils in aggravating organ injury in acute pancreatitis while the role of Kupffer cell activation is less obvious.

关键词： Acute pancreatitis Cytokines Neutrophils Kupffer cells Pulmonary injury

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Role of vascular endothelial growth factor as a critical neurotrophic factor for the survival and physiology of motoneurons

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Neural Regeneration Research 2023年第8期18卷 1691-1696页

作者： Paula m.Calvo Rosendo G.Hernández Rosa R.de la Cruz Angel m.pastor Departamento de Fisiología Facultad de BiologíaUniversidad de SevillaSevillaSpain

Vascular endothelial growth factor(VEGF)was discovered by its angiogenic ***,during evolution,it appeared earlier as a neurotrophic factor required for the development of the nervous system in invertebrates lacking a circulatory *** aimed at reviewing recent evidence indicating that VEGF has neuroprotective effects in neurons exposed to a variety of *** particular interest is the link established between VEGF and motoneurons,especially after the design of the VEGFδ/δmutant *** mice are characterized by low levels of VEGF and develop muscle weakness and motoneuron degeneration resembling amyotrophic lateral *** administration of VEGF through several routes to animal models of amyotrophic lateral sclerosis delays motor impairment and motoneuron degeneration and increases life *** are new recent advances in the role of VEGF in the physiology of *** experimental aims use the extraocular(abducens)motoneurons lesioned by axotomy as a model for studying VEGF *** abducens motoneurons exhibit severe alterations in their discharge activity and a loss of synaptic *** exogenous administration of VEGF to axotomized abducens motoneurons,either from the transected nerve or intraventricularly,fully restores the synaptic and discharge properties of abducens motoneurons,despite being *** addition,when an anti-VEGF neutralizing antibody is delivered from the muscle to intact,uninjured abducens motoneurons,these cells display alterations in their discharge pattern and a loss of synaptic boutons that resemble the state of *** these data indicate that VEGF is an essential neurotrophic factor for motoneurons.

关键词： abducens nucleus amyotrophic lateral sclerosis cell death extracellular single-unit recordings eye movements neurodegeneration oculomotor trophic factors

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Vascular endothelial growth factor：an essential neurotrophic factor for motoneurons？

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Neural Regeneration Research 2018年第7期13卷 1181-1182页

作者： Paula m.Calvo Angel m.pastor Rosa R.de la Cruz Departamento de Fisiologia Facultad de Biologia Universidad de Sevilla Sevilla Spain

Vascular endothelial growth factor（VEGF）,an angiogenic factor with neuroprotective effects：The VEGF was initially characterized by its vasculogenic and angiogenic activities and its capacity to promote vascular permeability（Yancopoulos et al.,2000）.VEGF is also known as VEGF-A and is the prototype member of a related group of five trophic factors,VEGF-B,VEGF-C,VEGF-D and placental growth factor（Pl GF;Lange et al.,2016）.

关键词： VEGFR Vascular endothelial growth factor:an essential neurotrophic factor for motoneurons

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Systemic analysis of metabolome reconfiguration in Arabidopsis after abiotic stressors uncovers metabolites that modulate defense against pathogens

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Plant Communications 2024年第1期5卷 55-68页

作者： Antoni Garcia-molina Victoria pastor Centre for Research in Agricultural Genomics(CRAG)CSIC-IRTA-UAB-UB C/Vall MorontaEdifici CRAG08193 Bellaterra(Cerdanyola del Valles)BarcelonaSpain Department of Biology Biochemistryand Natural SciencesSchool of Technology and Experimental SciencesUniversitat Jaume I12006 Castellode la PlanaSpain

Understanding plant immune responses is complex because of the high interdependence among biological processes in homeostatic ***,the integration of environmental cues causes network rewiring that interferes with defense ***,plants retain molecular signatures configured under abiotic stress periods to rapidly respond to recurrent stress,and these can alter *** changes imposed by abiotic stressors are persistent,although their impact on defense remains to be *** this study,we profiled metabolomes of Arabidopsis plants under several abiotic stress treatments applied individually or simultaneously to capture temporal trajectories in metabolite composition during adverse conditions and *** systemic analysis was performed to address the relevance of me-tabolome changes and extract central features to be tested in *** results demonstrate irreversibility in major fractions of metabolome changes as a general pattern in response to abiotic stress ***-tionalanalysisofmetabolomesandco-abundancenetworkspoints toconvergence inthereconfigurationof organic acid and secondary metabolite *** mutant lines for components related to these metabolic pathways showed altered defense capacities against different ***,our data suggest that sustained metabolome changes configured in adverse environments can act as mod-ulators of immune responses and provide evidence for a new layer of regulation in plant defense.

关键词： abiotic stress Arabidopsis biotic stress combinatorial stress metabolomics systems biology

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不可压缩塑性局部破坏问题的有效解法

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岩土工程学报 1999年第1期21卷 108-110页

作者：刘晓青夏颂佑 m.pastor 河海大学水利水电工程学院西班牙公共试验研究中心

１前言对于不可压缩或近似不可压缩问题的求解通常采用混合位移－压力（ｕ－ｐ）公式［１，２］，但由于离散的控制方程中与压力项对应的系数矩阵的主对角元接近于零，ｕ，ｐ插值函数的选择受到Ｂａｂｕｓｋａ－Ｂｒｅｚｚｉ稳定条件或... 详细信息

１前言对于不可压缩或近似不可压缩问题的求解通常采用混合位移－压力（ｕ－ｐ）公式［１，２］，但由于离散的控制方程中与压力项对应的系数矩阵的主对角元接近于零，ｕ，ｐ插值函数的选择受到Ｂａｂｕｓｋａ－Ｂｒｅｚｚｉ稳定条件或Ｚｉｅｎｋｉｅｗｉｃｚ－Ｔａｙｌｏ...

关键词：不可压缩塑性破坏机理网络法稳定性

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LevelSet方法求解三维大幅晃动问题的分步有限元法

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水动力学研究与进展（A辑） 2006年第4期21卷 433-438页

作者：赵兰浩李同春牛志伟 m.pastor 河海大学水利水电工程学院江苏南京210098 CEDEX and E.T.S.de Caminos MadridSpain

取与容器固结的坐标系,将外激励视为质量力,针对刚性容器内流体三维非线性大幅晃动问题,提出了在时间和空间上均具有二阶精度的两步Taylor-Galerk in分步有限元方法。该法首先显式地求解忽略压力梯度项的中间速度场,然后由压力泊松方程... 详细信息

取与容器固结的坐标系,将外激励视为质量力,针对刚性容器内流体三维非线性大幅晃动问题,提出了在时间和空间上均具有二阶精度的两步Taylor-Galerk in分步有限元方法。该法首先显式地求解忽略压力梯度项的中间速度场,然后由压力泊松方程求得压力场,再根据求得的压力对速度场进行修正。求解中利用Level-Set方法隐式地追踪自由面,即在每个时间步求解Level-Set函数随水流的输运方程,并通过迭代的方法对其进行重新初始化,以保持为距离的函数,从而达到捕捉自由面的目的。控制方程统一采用简单方便且具有较高精度的两步Taylor-Galerk in格式进行离散,并通过两个算例验证了本文数值方法的正确性和有效性。

关键词：大幅晃动 Level Set 两步Taylor—Galerkin 分步有限元

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刚性容器内流体非线性大幅晃动的数值模拟

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河海大学学报（自然科学版） 2006年第4期34卷 401-405页

作者：赵兰浩李同春牛志伟 m.pastor 河海大学水利水电工程学院江苏南京210098 西班牙国家公共实验研究中心

取与容器固结的坐标系,将外激励视为质量力,针对刚性容器内流体非线性大幅晃动问题,提出了在时间和空间上均具有二阶精度的两步Taylor-Galerkin分步有限元方法.该方法首先显式地求解忽略压力梯度项的中间速度场,然后通过压力泊松方程求... 详细信息

取与容器固结的坐标系,将外激励视为质量力,针对刚性容器内流体非线性大幅晃动问题,提出了在时间和空间上均具有二阶精度的两步Taylor-Galerkin分步有限元方法.该方法首先显式地求解忽略压力梯度项的中间速度场,然后通过压力泊松方程求得压力场,最后根据求得的压力对速度场进行修正.求解中利用Level Set方法隐式地追踪自由面,即在每个时间步求解Level-Set函数随水流的输运方程,并通过迭代方法对其重新进行初始化处理,使其保持为距离的函数,从而达到捕捉自由面的目的.控制方程统一采用简便且具有较高精度的两步Taylor-Galerkin格式进行离散.算例验证结果表明,该数值方法是正确和有效的.

关键词：刚性容器大幅晃动 Level Set 两步Taylor-Galerkin 分步有限元法

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