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Inflammatory bowel disease:Epidemiology,pathology and risk factors for hypercoagulability

World Journal of Gastroenterology 2014年第1期20卷 53-63页

作者： danuta owczarek Dorota Cibor Mikolaj K Glowacki Tomasz Rodacki Tomasz Mach Department of Gastroenterology Hepatology and Infectious DiseasesJagiellonian University Medical College31-531 KrakówPoland

Hypercoagulability observed in patients with inflammatory bowel diseases (IBD) may lead to thromboembolic events (TE), which affect the venous and arterial systems alike and are an important factor in patients’ morbidity and mortality. The risk of TE in IBD patients has been demonstrated to be approximately three-fold higher as compared to the general population. The pathogenesis of thrombosis in IBD patients is multifactorial and not fully explained. The most commonly listed factors include genetic and immune abnormalities, disequilibrium between procoagulant and anticoagulant factors, although recently, the role of endothelial damage as an IBD-triggering factor is underlined. Several studies report that the levels of some coagulation enzymes, including fibrinogen, factors V, VII, VIII, active factor XI, tissue factor, prothrombin fragment 1 + 2 and the thrombin-antithrombin complex, are altered in IBD patients. It has been demonstrated that there is a significant decrease of tissue plasminogen activator level, a marked increase of plasminogen activator inhibitor type 1 and thrombin-activable fibrinolysis inhibitor, a significantly lower level of antithrombin III and tissue factor pathway inhibitor. IBD patients have been also observed to produce an increased amount of various anticoagulant antibodies. Hyperhomocysteinemia, which is a potential risk factor for TE was also observed in some IBD patients. Further studies are necessary to assess the role of coagulation abnormalities in IBD etiology and to determine indications for thromboprophylactic treatment in patients at high risk of developing TE.

关键词： Crohn’ s disease, Hypercoagulation, Risk factors, Thrombosis, Ulcerative colitis

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Levels and activities of von Willebrand factor and metalloproteinase with thrombospondin type-1 motif, number 13 in inflammatory bowel diseases

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World Journal of Gastroenterology 2017年第26期23卷 4796-4805页

作者： Dorota Cibor danuta owczarek Saulius Butenas Kinga Salapa Tomasz Mach Anetta Undas Department of Gastroenterology Hepatology and Infectious DiseasesJagiellonian University Medical College Department of Biochemistry College of MedicineUniversity of Vermont Department of Bioinformatics and Telemedicine Jagiellonian University Medical College Institute of Cardiology Jagiellonian University Medical College

To evaluate the levels of von Willebrand factor (VWF) and metalloproteinase with thrombospondin type-1 motif, number 13 (ADAMTS13) in inflammatory bowel disease (IBD) and correlate them with the disease activity. METHODSConsecutive patients with IBD aged 18 years or older were enrolled in the study. Forty-seven patients with ulcerative colitis (UC), 38 with Crohn’s disease (CD), and 50 healthy controls were included. The white blood cell count, haematocrit, platelet count, fibrinogen, partial activated thromboplastin time, C-reactive protein, albumin, VWF antigen level (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), VWF collagen-binding activity (VWF:CB), and ADAMTS13 antigen level (ADAMTS13:Ag) and activity (ADAMTS13act) were measured. The following ratios were assessed: VWF:RCo/VWF:Ag, VWF:CB/VWF:Ag, VWF:Ag/ADAMTS13act, and ADAMTS13act/ADAMTS13:Ag. RESULTSCompared to controls, the odds ratio (OR) of an elevated VWF: Ag > 150% was 8.7 (95%CI: 2.7-28.1) in the UC group and 16.2 (95%CI: 4.8-54.0) in the CD group. VWF:CB was lower in UC patients, and active CD was associated with a higher VWF: RCo (+38%). The ORs of VWF:CB/VWF:Ag < 0.7 (a marker of acquired von Willebrand syndrome) in the UC and CD groups were 11.9 (95%CI: 4.4-32.4) and 13.3 (95%CI: 4.6-38.1), respectively. Active UC was associated with lower ADAMTS13:Ag (-23%) and ADAMTS13act (-20%) compared to UC in remission. Patients with active CD had a 15% lower ADAMTS13act than controls. The activity of UC, but not that of CD, was inversely correlated with ADAMTS13:Ag (r = -0.76) and ADAMTS13act (r = -0.81). CONCLUSIONComplex VWF-ADAMTS13-mediated mechanisms disturb haemostasis in IBD. A reduced WVF:CB is a risk factor for bleeding, while a lower ADAMTS13 level combined with an elevated VWF:Ag could predispose one to thrombosis.

关键词： ADAMTS13 Inflammatory bowel disease Thrombosis Acquired von Willebrand syndrome von Willebrand factor

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Diet and nutritional factors in inflammatory bowel diseases

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World Journal of Gastroenterology 2016年第3期22卷 895-905页

作者： danuta owczarek Tomasz Rodacki Renata Domagała-Rodacka Dorota Cibor Tomasz Mach Department of Gastroenterology Hepatology and Infectious DiseasesJagiellonian University Medical College31-531 CracowPoland Department of Food Chemistry and Nutrition Jagiellonian University Medical College30-688 CracowPoland

Inflammatory bowel disease(IBD) development is affected by complex interactions between environmental factors, changes in intestinal flora, various predisposing genetic properties and changes in the immune system. Dietary factors seem to play an underestimated role in the etiopathogenesis and course of the disease. However, research about food and IBD is conflicting. An excessive consumption of sugar, animal fat and linoleic acid is considered a risk factor for IBD development, whereas a high fiber diet and citrus fruit consumption may play a protective role. Also, appropriate nutrition in particular periods of the disease may facilitate achieving or prolonging remissions and most of all, improve the quality of life for patients. During disease exacerbation, a low fiber diet is recommended for most patients. In the remission time, an excessive consumption of alcohol and sulfur products may have a negative effect on the disease course. Attempts are also made at employing diets composed in detail in order to supplement IBD therapy. A diet with a modified carbohydrate composition, a semi-vegetarian diet and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols are under investigation. Due to chronic inflammation as well as side effects of chronically used medications, patients with IBD are also at increased risk of nutritional factor deficiencies, including iron, calcium, vitamin D, vitamin B12, folic acid, zinc, magnesium and vitamin A. It should also be remembered that there is no single common diet suitable for all IBD patients; each of them is unique and dietary recommendations must be individually developed for each patient, depending on the course of the disease, past surgical procedures and type of pharmacotherapy.

关键词： Crohn's disease Diet Nutrition Supplementation Ulcerative colitis

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Endothelial dysfunction in inflammatory bowel diseases:Pathogenesis,assessment and implications

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World Journal of Gastroenterology 2016年第3期22卷 1067-1077页

作者： Dorota Cibor Renata Domagala-Rodacka Tomasz Rodacki Artur Jurczyszyn Tomasz Mach danuta owczarek Department of Gastroenterology Hepatology and Infectious DiseasesJagiellonian University Medical College31-531 CracowPoland Master of Pharmacy 31-531 CracowPoland Department of Food Chemistry and Nutrition Jagiellonian University Medical College30-688 CracowPoland Department of Hematology Jagiellonian University Medical College31-531 CracowPoland

Endothelial dysfunction is considered one of the etiological factors of inflammatory bowel disease(IBD). An inflammatory process leads to functional and structural changes in the vascular endothelium. An increase of leukocyte adhesiveness and leukocyte diapedesis, as well as an increased vascular smooth muscle tone and procoagulant activity is observed. Structural changes of the vascular endothelium comprise as well capillary and venule remodeling and proliferation of endothelial cells. Hypoxia in the inflammatory area stimulates angiogenesis by upregulation of vascular endothelial growth factor, fibroblast growth factor and tumor necrosis factor-α. Inflammatory mediators also alter the lymphatic vessel function and impair lymph flow, exacerbating tissue edema and accumulation of dead cells and bacteria. The endothelial dysfunction might be diagnosed by the use of two main methods: physical and biochemical. Physical methods are based on the assessment of large arteries vasodilatation in response to an increased flow and receptors stimulation. Flowmediated vasodilatation(FMD) is the method that is the most widely used; however, it is less sensitive in detecting early changes of the endothelium function. Most of the studies demonstrated a decrease of FMD in IBD patients but no changes in the carotic intima-media thickness. Biochemical methods of detecting the endothelial dysfunction are based on the assessment of the synthesis of compounds produced both by the normal and damaged endothelium. The endothelial dysfunction is considered an initial step in the pathogenesis of atherosclerosis in the general population. In IBD patients, the risk of cardiovascular diseases is controversial. Large, prospective studies are needed to establish the role of particular medications or dietary elements in the endothelial dysfunction as well to determine the real risk of cardiovascular diseases.

关键词： Biomarkers Cytokines Diagnosis Endothelialdysfunction Inflammatory bowel diseases Inflammation Microvasculature

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IL28B polymorphism as a predictor of antiviral response in chronic hepatitis C

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World Journal of Gastroenterology 2012年第35期18卷 4892-4897页

作者： Andrzej Ciela Monika Bociaga-Jasik Iwona Sobczyk-Krupiarz Mikolaj K Glowacki danuta owczarek Dorota Cibor Marek Sanak Tomasz Mach Department of Gastroenterology Hepatology and Infectious DiseasesJagiellonian University Medical College Department of Molecular Biology and Clinical Genetics II Department of Internal MedicineJagiellonian University Medical College

AIM： To evaluate the effect of single nucleotide poly- morphisms of interleukin （IL）-28B, rs12979860 on progression and treatment response in chronic hepatitis C. METHODS： Patients （n = 64; 37 men, 27 women; mean age, 44 ＋ 12 years） with chronic hepatitis C, genotype 1, received treatment with peg-interferon plus ribavirin. Genotyping of rs12979860 was per- formed on peripheral blood DNA. Histopathological assessment of necroinflammatory grade and fibrosis stage were scored using the METAVIR system on a liver biopsy sample before treatment. Serum viral load, ami- notransferase activity, and insulin level were measured. Insulin resistance index, body mass index, waist/hip ratio, percentage of body fat and fibrosis progression rate were calculated. Applied dose of interferon and ribavirin, platelet and neutrophil count and hemoglobin level were measured. RESULTS： A sustained virological response （SVR） was significantly associated with IL28B polymorphism （CC vs -l-r allele： odds ratio （OR）, 25; CC vs CT allele： OR, 5.4）, inflammation activity （G 〈 1 vs G 〉 1： OR, 3.9）, fibrosis （F 〈 1 vs F 〉 1： OR, 5.9）, platelet count （〉 200 × 109/L vs 〈 200 ×109/L： OR, 4.7; OR in patients with genotype CT： 12.8）, fatty liver （absence vs presence of steatosis： OR, 4.8）, insulin resistance index （〈 2.5 vs 〉 2.5： OR, 3.9）, and baseline HCV viral load （〈 106 IU/mL vs 〉 106 IU/mL： OR, 3.0）. There was no association with age, sex, aminotransferases activity, body mass index, waist/hip ratio, or percentage body fat. There was borderline significance （P = 0.064） of increased fibrosis in patients with the I-I allele, and no differences in the insulin resistance index between groups of patients with CC, CT and -IF alleles （P = 0.12）. Spearman＇s rank correlation coefficient between insulin resistance and stage of fibrosis and body mass index was r = 0.618 and r = 0.605, respectively （P 〈 0.001）. Significant dif- ferences were found in the insulin resistance index （P = 0.01） between patients wit

关键词： IL28B polymorphism Hepatitis C Fibrosis Progression Peg-interferon alpha Sustained viral re-sponse

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Intrahepatic expression of genes related to metabotropic receptors in chronic hepatitis

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World Journal of Gastroenterology 2012年第31期18卷 4156-4161页

作者： Andrzej Ciesla Maciej Kusmider Agata Faron-Górecka Marta Dziedzicka-Wasylewska Monika Bocisga-Jasik danuta owczarek Irena Cieko-Michalska Dorota Cibor Tomasz Mach Department of Gastroenterology Hepatology and Infectious DiseasesJagiellonian University Medical College31-521 KrakówPoland Institute of Pharmacology Polish Academy of Sciences31-343 KrakówPoland

AIM： To screen for genes related to metabotropic re- ceptors that might be involved in the development of chronic hepatitis. METHODS： Assessment of 20 genes associated with metabotropic receptors was performed in liver speci- mens obtained by punch biopsy from 12 patients with autoimmune and chronic hepatitis type B and C. For this purpose, a microarray with low integrity grade and with oligonucleotide DNA probes complementary to target transcripts was used. Evaluation of gene expression was performed in relation to transcript level, correlation between samples and grouping of clinical parameters used in chronic hepatitis assessment. Clini- cal markers of chronic hepatitis included alanine and aspartate aminotransferase, ~,-glutamyltranspeptidase, alkaline phosphatase and cholinesterase activity, levels of iron ions, total cholesterol, triglycerides, albumin, glucose, hemoglobin, platelets, histological analysis of inflammatory and necrotic status, fibrosis according to METAVIR score, steatosis, as well as anthropometric body mass index, waist/hip index, percentage of adi- pose tissue and liver size in ultrasound examination. Gender, age, concomitant diseases and drugs were also taken into account. Validation of oligonucleotide microarray gene expression results was done with the use of quantitative real-time polymerase chain reaction （qRT-PCR）. RESULTS： The highest （0.002 〈 P 〈 0.046） expres- sion among genes encoding main components of metabotropic receptor pathways, such as the a subunit of G-coupled protein, phosphoinositol-dependent pro- tein kinase or arrestin was comparable to that of an- giotensinogen synthesized in the liver. Carcinogenesis suppressor genes, such as chemokine ligand 4, tran- scription factor early growth response protein 1 and lysophosphatidic acid receptor, were characterized by the lowest expression （0.002 〈 P 〈 0.046）, while the factor potentially triggering hepatic cancer, transcrip- tion factor JUN-B, had a 20-fold higher expression. T

关键词： Metabotropic receptors Gene expression DNA oligonucleotides Quantitative real-time poly-merase chain reaction Chronic hepatitis

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Foraminiferal micro-buildups(“reefs”)in the Wuchiapingian basin facies of the basal Zechstein carbonates in western Poland

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Journal of Palaeogeography 2021年第4期10卷 463-481页

作者： Tadeusz Marek Peryt danuta Peryt Polish Geological Institute-National Research Institute Rakowiecka 400-975WarszawaPoland Institute of Paleobiology Polish Academy of SciencesTwarda 51/5500-818WarszawaPoland

Encrusting foraminifers locally can play an essential reef-forming role such as in the Carnian fossiliferous Hallstatt Limestones of Austria where a dense succession of hardgrounds occurs with numerous small buildups(up to 2 cm high)composed of sessile *** foraminiferal micro-buildups occur in a 10-cm-thick bed in the basinal facies in the basal Zechstein(Upper Permian)strata in the Radlin 60 borehole,in western *** micro-buildups of presumably columnar habit account for up to a half of the *** growth of columns was interrupted by hiatal surfaces,although usually the growth of columns was restored *** the upper part of the bed with foraminiferal micro-buildups,the foraminiferal encrustations become visibly less abundant,and in most cases,they have a shape of less regular *** bed with foraminiferal micro-buildups abounds in closely spaced discontinuity(hiatal)surfaces,occasionally encrusted by *** foraminifers in the bed with foraminiferal micro-buildups are accompanied by various encrusting organisms,possibly microbes;they are grouped under the name *** the intercolumnar spaces,common Midiella *** deposition,the conditions were mostly suboxic,and various types of ferruginous morphs,common in the lower part of the bed,suggest that dysoxic-anoxic interfaces produced various microaerophilic environments for *** environmental conditions during the deposition of the upper part of the bed were very similar to those characterizing the starved basin environment in which the bioclastic-peloidal and oncoidal sediments in the Zechstein Limestone have been *** turn,the lower part of the bed registers the transition from normal(=not starved)marine conditions,with a clear chemocline,to the starved basin *** deposition of the bed was coeval with the Kupferschiefer deposition based on the correlation ofδ13C curves,which implies that the previous str

关键词： Condensed Zechstein Limestone Micro-buildups Encrusting foraminifers Stable isotopes Depositional environment Zechstein stratigraphy Hiatal surfaces

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Role of quantum dots nanoparticles in the chemical treatment of colored wastewater: Catalysts or additional pollutants

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Journal of Environmental Sciences 2011年第9期23卷 1479-1485页

作者： Hrvoje Kusic danuta Leszczynska Natalija Koprivanac Igor Peterne Civil and Environmental Engineering Department Jackson State University Faculty of Chemical Engineering and Technology University of Zagreb

The objective of the study was to investigate the presence and the activity of quantum dots nanoparticles in colored *** special interest is devoted to the investigation of their role in the typical treatment of water or wastewater,studying their influence on the effectiveness of applied treatments *** standard chemical processes for water treatment and disinfection （direct UV photolysis and direct ozonation） were applied for the degradation of colored organic pollutant,reactive azo dye,in the presence/absence of CdSe/ZnS core-shells quantum *** obtained results indicated that investigated nanoparticles inhibit the overall efficiency of applied processes,especially in the case of direct UV photolysis,although catalytic effect might be expected in part due to the semiconductor nature of quantum *** results lead to a conclusion that CdSe/ZnS nanoparticles behave as additional pollutants in the *** should be removed from the system prior the treatment,because their presence could decrease the efficiency,i.e.,prolong the time of treatment and correspondingly increase the costs of the treatment process.

关键词： wastewater treatment CdSe/ZnS core-shells reactive azo dye UV irradiation ozone

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Marine transgression(s) to evaporite basin:The case of middle Miocene (Badenian) gypsum in the Central Paratethys, SE Poland

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Journal of Palaeogeography 2020年第3期9卷 335-352页

作者： danuta Peryt Przemyslaw Gedl Tadeusz Marek Peryt Institute of Paleobiology Polish Academy of SciencesTwarda 51/5500-818 WarszawaPoland institute of Geological Sciences Polish Academy of SciencesResearch Centre in CracowSenacka 131-002 KrakowPoland Polish Geological Institute-National Research Institute Rakowiecka 400-975 WarszawaPoland

The middle Miocene Badenian evaporite basin of the Carpathian Foredeep Basin was a saline lake, separated by a barrier from the sea and supplied with seawater seeping through the barrier or overflowing it occasionally in the form of short-lived marine transgressions. Such transgressions could leave behind marine microfossils in marly clay intercalations. One of them(2.3 m thick) occurs in the uppermost part of the sulphate sequence, in the unit ‘o’, in the Babczyn 2 borehole section. It contains marine palynomorphs(dinoflagellate cysts) and foraminiferal assemblages indicating a marine environment. The low-diversity benthic foraminiferal assemblages are dominated by opportunistic, shallow infaunally living species, preferring muddy or clayey substrate for thriving, brackish to normal marine salinity, and inner shelf environment. Dinoflagellate cyst assemblages, although taxonomically impoverished, consist of marine species;euryhaline forms that tolerate increased salinity are missing. Relatively common microfossils found in clay intercalations within gypsum have important palaeogeographical implications:they strongly suggest that there existed an additional inflow channel supplying the Polish Carpathian Basin from the south during the evaporite deposition and afterwards.

关键词： Evaporite basins Transgression Microfossils Badenian Palaeogeography Paratethys

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Otilonium bromide in irritable bowel syndrome:A dose-ranging randomized double-blind placebo-controlled trial

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World Journal of Gastroenterology 2014年第34期20卷 12283-12291页

作者： danuta Chmielewska-Wilkoń Giorgio Reggiardo Colin Gerard Egan Department of Gastrointestinal Endoscopy Gabinet Endoskopii Przewodu PokarmowegoSzewska31-009 KrakowPoland Medi Service World Trade Center16149 GenoaItaly Primula Multimedia SRL 56121 PisaItaly

AIM: To examine the efficacy and safety of otilonium bromide (OB) in treatment-sensitive functional irritable bowel syndrome (IBS) clinical parameters.

关键词： Otilonium bromide Irritable bowel syndrome Spasmolytic Acute treatment

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