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Multiorgan chronic inflammatory hepatobiliary pancreatic murine model deficient in tumor necrosis factor receptors 1 and 2

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World Journal of Gastroenterology 2016年第21期22卷 4988-4998页

作者： helieh s oz Department of Physiology and Internal Medicine College of Medicine University of Kentucky Medical Center

AIM: To provoke persistent/chronic multiorgan inflammatory response and to contribute to stones formation followed by fibrosis in hepatobiliary and pancreatic ***: Tumor necrosis factor receptors 1 and 2 (TNFR1/R2) deficient mice reared in-house were given dibutyltin dichloride (DBTC) twice within 10 d by oral gavage delivery. sham control animals received vehicle treatment and naïve animals remained untreated throughout the study. Animals were monitored daily for symptoms of pain and discomfort. The abdominal and hindpaw hypersensitivity were assessed with von Frey microfilaments. Exploratory behaviors were recorded at the baseline, after initiation of treatment, and before study termination. Histopathological changes were examined postmortem in tissues. Collagen accumulation and fibrosis were confirmed with sirius Red ***: Animals lost weight after oral administration of DBTC and developed persistent inflammatory abdominal and hindpaw hypersensitivity compared to sham-treated controls (P se pain related secondary mechanical hypersensitivity responses increased more than 2-fold in DBTC-treated animals. The drastically diminished rearing and grooming rates persisted after DBTC administration throughout the study. Gross as well as micropathology at one month confirmed that animals treated with DBTC developed chronic hepatobiliary injuries evidenced with activation of stellate cells, multifocal necrosis, fatty degeneration of hepatocytes, periportal infiltration of inflammatory cells, and prominent biliary ductal dilation. The severity of hepatitis was scored 3.7 ± 0.2 (severe) in DBTC-treated animals vs score 0 (normal) in sham-treated animals. Fibrotic thickening was extensive around portal ducts, in hepatic parenchyma as well as in lobular pancreatic structures and confirmed with sirius Red histopathology. In addition, pancreatic microarchitecture was presented with distortion of islets, and parenchyma,

关键词： Inflammatory pain Multiorgan Hepatitis Pancreatitis Calculi formation Gall bladder Hepatobiliary inflammation

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Gene expression profiling and endothelin in acute experimental pancreatitis

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World Journal of Gastroenterology 2012年第32期18卷 4257-4269页

作者： helieh s oz Ying Lu Louis P Vera-Portocarrero Pei Ge Ada silos-santiago Karin N Westlund Department of Physiology College of Medicine University of Kentucky Medical Center Lexington KY 40536 United States Department of Internal Medicine College of Medicine University of Kentucky Medical Center Lexington KY 40536 United States Department of Anatomy and Neuroscience University of Texas Medical Branch Galveston TX 77555 United States Medtronics Inc. Minneapolis MN 55432 United States Ironwood Pharmaceuticals Cambridge Ironwood Pharmaceuticals Cambridge MA 02141 United States

AIM:To analyze gene expression profiles in an experimental pancreatitis and provide functional reversal of hypersensitivity with candidate gene endothelin-1 ***:Dibutyltin dichloride(DBTC) is a chemical used as a polyvinyl carbonate stabilizer/catalyzer,biocide in agriculture,antifouling agent in paint and *** induces an acute pancreatitis flare through generation of reactive oxygen ***-inbred rats received a single *** with either DBTC or *** cord and dorsal root ganglia(DRG) were taken at the peak of inflammation and processed for transcriptional profiling with a cDNA microarray biased for rat brain-specific *** a second study,groups of animals with DBTC-induced pancreatitis were treated with endothelin(ET) receptor antagonists [ET-A(BQ123) and ET-B BQ788)].spontaneous pain related mechanical and thermal hypersensitivity were *** analysis was performed using anti-ET-A and ET-B antibodies on sections from pancreatic tissues and DRG of the T10-12 spinal ***:Animals developed acute pancreatic inflammation persisting 7-10 d as confirmed by pathological studies(edema in parenchyma,loss of pancreatic architecture and islets,infiltration of inflammatory cells,neutrophil and mononuclear cells,degeneration,vacuolization and necrosis of acinar cells) and the painrelated behaviors(cutaneous secondary mechanical and thermal hypersensitivity).Gene expression profile was different in the spinal cord from animals with pancreatitis compared to the vehicle control *** 260 up-regulated and 60 down-regulated unique genes could be classified into 8 functional gene families:circulatory/acute phase/immunomodulatory;extracellular matrix;structural;channel/receptor/transporter;signaling transduction;transcription/translation-related;antioxidants/chaperones/heat shock;pancreatic and other ***-1 was among the 52 candidate genes upregulated greater than 2-fold in animals with panc

关键词： Gene expression Endothelin receptors Pancreatitis Pain Dibutyltin dichloride Hypersensitivity Hyperalgesia

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Novel synergistic Protective Efficacy of Atovaquone and Diclazuril on Fetal-Maternal Toxoplasmosis

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International Journal of Clinical Medicine 2014年第15期5卷 921-932页

作者： helieh s. oz Department of Internal Medicine University of Kentucky Medical Center Lexington KY USA

Over 1 billion people globally are estimated to be infected with Toxoplasma gondii with severe or unknown consequences and no safe and effective therapies are available against congenital or persistent chronic infection. We propose that atovaquone and diclazuril synergistically protect against fetal-maternal toxoplasmosis. Methods: Programmed pregnant mice were treated with atovaquone and diclazuril monotherapy, or combined (atovaquone + diclazuril) therapy and infected with tachyzoites (0, 300, 600) and the course of infection was studied. Results: Infected dams with low dose (300) developed moderate toxoplasmosis complications and treatments were similarly effective with minor differences between monotherapies. In contrast, major differences were observed amongst varied treatments during high-dose (600) infection and severe related-toxoplasmosis complications as follows. Dams developed hydrothorax, ascities and excess weight gain. Combined therapy (P sser extent diclazuril monotherapy (P 0.05) protected dams from excess weight, hydrothorax, and ascities. Infected dams exhibited splenomegaly, hepatomegaly and severe hepatitis. Combined therapy synergistically normalized pathology (P sser degree monotherapy (diclazuril P 0.01, and atovaquone P 0.05) protected dams from hepatitis and splemomegaly. Additionally, behavioral response to pain stimuli and fetal weight and fetal numbers were significantly preserved in treated dams. Conclusions: This is the first report describing combined atovaquone and diclazuril therapy a) to be safe in pregnancy, b) to exert novel synergistic effects, and c) to protect dams and their nested fetuses against adverse effects of severe toxoplasmosis.

关键词： Toxoplasma Atovaquone Diclazuril synergistic Protection Fetal Maternal Congenital Toxoplasmosis Pregnancy Gastroenteritis

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Diclazuril Protects against Maternal Gastrointestinal syndrome and Congenital Toxoplasmosis

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International Journal of Clinical Medicine 2014年第3期5卷 93-101页

作者： helieh s. oz Thomas Tobin Department Internal Medicine University of Kentucky Medical Center Lexington USA The Maxwell H. Gluck Equine Research Center Department of Veterinary Science College of Agriculture University of Kentucky Lexington USA

Background: Toxoplasmosis is a common cause of foodborne, gastrointestinal and congenital syndrome with particularly severe or unknown health consequences. There is no safe and effective preventive or therapeutic modality against congenital toxoplasmosis or to eliminate the persistent chronic infection. Hypothesis: Diclazuril to be safe in pregnancy and effective against gastrointestinal toxoplasmosis. Methods: CD1 programmed pregnant mice were divided into groups and administered a diet containing diclazuril, or sham control. Treatments were initiated on Day 5 of pregnancy and continued until Day 16 when dams were euthanatized. On Day 8 of pregnancy dams were infected intraperitoneally with escalating doses of tachyzoites (0, 100, 300, 600) from Type II strain. Dams were monitored daily for distress, pain, and abortion and samples collected at the end of the experiments. Results: Infected dams developed moderate to severe Toxoplasma related complications in tachyzoites dose dependent manner. Animals became anemic and showed hydrothorax, and ascities. Diclazuril effectively protected dams from ascities and anemia (p s showed splenomegaly, with massive infiltration of epithelioid cells compared with the protective effect of diclazuril in treated animals. Infected dams exhibited severe hepatitis (score 0 to 4 scale = 3.5 ± 0.01) with influx of inflammatory and plasma cells, dysplastic hepatocytes, multinucleated giant cell transformation and hepatic cells necrosis. Diclazuril treatment significantly protected dams from hepatitis, also in tachyzoites dose (100, 300, 600) dependent manner (respectively infected-treated versus infected controls, p s, and macrophages and microabscess formations in the cryptic structures, with significant improvement in diclazuril treated animals. Additionally, the number of fetuses, fetal length and fetal weight were preserved in diclazuril treated dams. Conclusio

关键词： Diclazuril Gastrointestinal Hepatitis Colitis Pregnancy Congenital Toxoplasmosis

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Green Tea Polyphenols Mediated Apoptosis in Intestinal Epithelial Cells by a Fadd-Dependent Pathway

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Journal of Cancer Therapy 2010年第3期1卷 105-113页

作者： helieh s. oz Jeffrey L. Ebersole Center for Oral Health Research College of Dentistry University of Kentucky Medical Center Lexington KY.

Colorectal cancer is the most common malignant complication in patients with chronic inflammatory bowel disease (IBD). In addition, these patients are at risk for developing painful complications during chemotherapy due to cytotoxic effects of drugs currently in use. Past studies have suggested a protective effect of tea consumption on gastrointestinal (GI) malignancies. Green tea polyphenols (GrTP) inhibited carcinogen-induced GI tumors in rodents and induced apoptosis in various carcinoma cell lines. We hypothesized that GrTP and its polyphenolic compounds regulate apoptosis in the intestinal epithelia. In this study, the effects of GrTP and its polyphenolics on apoptosis was evaluated in intestinal epithelial, IEC-6, cells grown to 85% confluency. GrTP (400-800 mg/ml) induced DNA fragmentation in a dose dependent fashion. Higher concentrations (> 800 mg/ml) induced a mixed apoptosis and cytolysis. Epithelial cells exposed to GrTP and a major polyphenol, EGCG, but not EGC or EC, increased caspase activities in a time and dose dependent manner. The caspase inhibitors rescued cells from GrTP and EGCG-induced cell death. Concomitantly, GrTP resulted in activation of fatty acid synthase (Fas)-associated protein with death domain (FADD) and recruitment to Fas/CD95 domain 30 minutes following treatment. While GrTP also blocked NF-?B activation, an NF-?B inhibitor (MG132) only promoted cytolysis. In conclusion, these data demonstrated GrTP and EGCG induced apoptosis in intestinal epithelia mediated by caspase-8 through a FADD dependent pathway. Future investigation may warrant preventive as well as therapeutic strategies for GrTP in GI malignancy.

关键词： Intestinal Epithelial Cells Green Tea Polyphenols EGCG Apoptosis

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Narrow versus broad:sexual dimorphism in the wing form of western European species of the subgenus Avaritia(Culicoides,Ceratopogonidae)

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Integrative Zoology 2021年第5期16卷 769-784页

作者： Francesc MUÑoz-MUÑoz Nonito PAGÈs Ana.F.DURAO Marion ENGLAND Doreen WERNER sandra TALAVERA Departament de Biologia Animal de Biologia Vegetal i d’EcologiaFacultat de BiociènciesUniversitat Autònoma de BarcelonaBarcelonaSpain Centre de Recerca en sanitat Animal(CResA) UAB-IRTACampus de la Universitat Autònoma de BarcelonaBarcelonaSpain CIRAD UMR ASTREGuadeloupeFrance AsTRE CIRADINRAeUniversitéde MontpellierMontpellierFrance The Pirbright Institute SurreyUK Leibniz-Centre for Agricultural Landscape Research MünchebergGermany

While wing form is known to differ between males and females of the genus Culicoides,detailed studies of sexual dimorphism are *** this study,we analyze sex-specific differences in the wing form of 5 species of the subgenus Avaritia,using geometric morphometrics and comparative phylogenetic *** results confirm the existence of marked sexual dimorphism in the wing form of the studied species and reveal for the first time that while there is a shared general pattern of sexual shape dimorphism within the subgenus,sexual size dimorphism,and particular features of sexual shape dimorphism differ among *** shape dimorphism was found to be poorly associated to size and the evolutionary history of the *** tight association of sexual shape dimorphism with aspect ratio suggests that the shape of the wing is optimized for the type of flight of each sex,that is,dispersal flight in females versus aerobatic flight in ***,the fact that interspecific shape differences are greater and more strongly associated to aspect ratio in males than in females might be indicating that in males the selective pressures affecting flight performance characteristics are more heterogeneous and/or stronger than in females among the studied species.

关键词： aspect ratio geometric morphometrics phylogenetic signal shape size

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Precipitation kinetics of carbides during cyclical and isothermal aging of 2.25Cr–1Mo steel and its effect on mechanical properties

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Journal of Iron and steel Research International 2021年第10期28卷 1282-1290页

作者： Maribel Leticia saucedo-Muñoz EsIQIE Instituto Politécnico NacionalMexico07300Mexico

The carbide precipitation was analyzed during aging of 2.25Cr–1Mo steel at 550℃.The as-received steel was aged in two different manners:the first treatment was an isothermal aging at 550℃ for time up to 1000 h,and the second one was carried out by a cyclical aging,which consisted of aging at 550℃ for 1 h,water quenching at room temperature and then newly heating at 550℃.This procedure was repeated up to 300 *** M_(23)C_(6) and M6C carbide precipitation took place intragranularly and intergranularly for both aging *** carbide coarsening was detected to occur with the increasing aging ***,the growth kinetics of precipitation occurred more rapidly in the case of cyclical *** specimen hardness decreased with the aging time in both cases;however,it occurred in shorter aging time for the cyclical *** testing indicated the increase in ductility with the aging time,and the cyclically aged specimens showed larger ductility than the isothermally aged specimens.

关键词： 2.25Cr-1Mo steel Precipitation Isothermal heating Cyclical heating Mechanical property

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Capsule endoscopy

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World Journal of Gastroenterology 2009年第13期15卷 1584-1586页

作者： Miguel Muoz-Navas Gastroenterology Department University Clinic of Navarra

Capsule endoscopy(CE) is a simple,safe,non-invasive,reliable technique,well accepted and tolerated by the patients,which allows complete exploration of the small *** advent of CE in 2000 has dramatically changed the diagnosis and management of many diseases of the small intestine,such as obscure gastrointestinal bleeding,Crohn's disease,small bowel tumors,polyposis syndromes,*** has become the gold standard for the diagnosis of most diseases of the small *** this technique has also been used for esophageal and colonic diseases.

关键词： Capsule endoscopy small intestine Gastrointestinal hemorrhage Crohn's disease Gastro-intestinal neoplasms Intestinal polyposis

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soil and Vegetation seasonal Changes in the Grazing Andean Mountain Grasslands

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Journal of Mountain science 2014年第5期11卷 1123-1137页

作者： MU?oz María ángeles FAZ ángel sustainable Use Management and Reclamation Soil and Water Research Group Agriculture and Science Technology Department Technical University of Cartagena

Andean grasslands ecosystems are fragile environments with rigorous climatologic conditions and low and variable food for the grazing. The Apolobamba area is located in the Bolivian Andean Mountains. Its high grasslands provide a natural habitat for wild and domestic camelids such as vicuna(Vicugna vicugna) and alpaca(Lama pacos). The botanical diversity plays an essential role in maintaining vital ecosystem functions. The objectives of this research were to determine the seasonal changes in soil properties, to study the vegetation changes during the wet and dry seasons and the influence of soil properties and camelid densities on the vegetation in the Apolobamba grasslands. Four zones with different vicuna populations were selected to be studied. The following soil parameters were determined: total organic carbon, total nitrogen, available phosphorous, cation exchange capacity, exchangeable cations, pH and texture. The vegetation season changes were studied through botanical identification, above-ground biomass, plant cover and species richness. Results showed that some soil properties such as C/N ratio, CEC, silt and clay percentages kept stable against the seasonal changes. Generally, soil nutrients were relatively higher during the dry season in the surface and subsurface. The results did not point out the predominant vegetation growth during the wet season. The seasonal vegetation growth depended on each species. Thegood soil fertility corresponded to the highest plant cover. soil fertility presented no influence on the above-ground biomass of the collected species. The negative influence of camelid grazing on soil properties could not be assessed. However, overgrazing could affect some plant species. Therefore, protection is needed in order to preserve the biodiversity in the Andean mountain grasslands.

关键词： Biodiversity Camelid grazing High grasslands Plant communities soil properties

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Donor risk factors in pancreas transplantation

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World Journal of Transplantation 2020年第12期10卷 372-380页

作者： Luis Muñoz-Bellvís Jaime López-sánchez Department of General&Gastrointestinal surgery Hospital Universitario de SalamancaUniversidad de SalamancaSalamanca 37007Spain salamanca Biomedical Research Institute(IBsAL) Universidad de SalamancaSalamanca 37007Spain

The aim of the work was to analyze and expose the donor and recipient riskfactors in pancreas transplantation. In the following paper, we exposed the 2018spanish Consensus Document on Donor and Recipient selection Criteria forPancreas Transplantation. An assessment of the previous selection Criteria forDonors and Recipients of Pancreas Transplantation, published in 2005 by thespanish Pancreas Transplant Group (GETP) and the National TransplantOrganization (ONT) was performed. A literature review was performed usingCochrane Library, PubMed and Google scholar databases. some of the followingterms were used for the literature search: “Diabetes Mellitus,” “PancreasTransplantation,” “Insulin-secreting Cells,” “Pancreas Allograft Thrombosis,”“Allograft Pancreatitis,” “Donors’ Risk Factors,” “Recipients’ Risk Factors,”“Pancreas Allograft Rejection” and “Pancreas Allograft survival.” After anextended search, different inclusion criteria were established. Articles anddocuments with abstracts of full text and in English or spanish language wereselected. subsequently, different scientific meetings took place during 2015 and2016 by the GETP. Finally, the updated criteria were published by the GETP andONT in 2018. several risk factors have been described in pancreas transplantationthat can be divided into donor risk factors: Advanced age (> 50 years);high bodymass index (BMI) (> 30 kg/m2);cause of death (e.g., stroke);previoushyperglycemia;hyperamylasemia;cold ischemia time (greater than 8 or 12 h,depending on the type of donation);the use of vasopressors in the intensive careunit or cardiac arrest;and the macroscopic aspect of the pancreas allograft. Thefollowing are recipient risk factors: Advanced age (> 50 years);active smoking;high BMI (> 30 kg/m2);and peripheral artery disease or sensorimotorpolyneuropathy. Based on the aforementioned parameters, different selectioncriteria have been established for the recipients depending on the type of pancreastransplantation. Knowledge

关键词： Pancreas transplantation Pancreas donor Pancreas recipient Diabetes mellitus Risk factors Graft rejection

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