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UDp-glucuronosyltransferases mediate coffee-associated reduction of liver fibrosis in bile duct ligated humanized transgenic UGT1A mice

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Hepatobiliary Surgery and Nutrition 2021年第6期10卷 766-781页

作者： Steffen Landerer Sandra Kalthoff christian p.strassburg Department of Internal Medicine I University Hospital BonnVenusberg-Campus 1BonnGermany

Background:Coffee consumption has been shown to reduce the risk of liver fibrosis and is capable of inducing human UDp-glucuronosyltransferase(UGT)1A genes.UGT1A enzymes act as indirect antioxidants catalyzing the elimination of reactive metabolites,which in turn are potent initiators of profibrotic mechanisms.The aim of this study was to analyze the role of UGT1A genes as effectors of the protective properties of coffee in bile duct ligation(BDL)induced liver fibrosis.Methods:Fourteen days BDL with and without coffee pre-and co-treatment was performed in htgUGT1A-WT and htgUGT1A-SNp mice.Hepatic UGT1A mRNA expression levels,serum bilirubin and aminotransferase activities were determined.Liver fibrosis was assessed by collagen deposition,computational analysis of Sirius red tissue staining and expression of profibrotic marker genes.Oxidative stress was measured by hepatic peroxidase concentrations and immunofluorescence staining.Results:UGT1A transcription was differentially activated in the livers of htgUGT1A-WT mice after BDL,in contrast to a reduced or absent induction in the presence of SNps.Co-treated(coffee+BDL)htgUGT1A-WT-mice showed significantly increased UGT1A expression and protein levels and a considerably higher induction compared to water drinking WT mice(BDL),whereas in co-treated htgUGT1A-SNp mice absolute expression levels remained below those observed in htgUGT1A-WT mice.Collagen deposition,oxidative stress and the expression of profibrotic markers inversely correlated with UGT1A expression levels in htgUGT1A-WT and SNp mice after BDL and coffee+BDL co-treatment.Conclusions:Coffee exerts hepatoprotective and antioxidative effects via activation of UGT1A enzymes.Attenuated hepatic fibrosis as a result of coffee-mediated UGT1A induction during cholestasis was detected,while the protective action of coffee was lower in a common low-function UGT1A SNp haplotype present in 10%of the Caucasian population.This study suggests that coffee consumption might constitute a potential strategy to support the c

关键词： Glucuronidation cholestasis liver fibrosis coffee oxidative stress

Hepatic encephalopathy before and neurological complications after liver transplantation have no impact on the employment status 1 year after transplantation

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World Journal of Hepatology 2017年第10期9卷 519-532页

作者： Henning pflugrad Anita B Tryc Annemarie Goldbecker christian p strassburg Hannelore Barg-Hock Jürgen Klempnauer Karin Weissenborn Department of Neurology Hannover Medical School Integrated Research and Treatment Centre Transplantation Department of Gastroenterology Hepatology and EndocrinologyHannover Medical School Department of Medicine I University Hospital Bonn Clinic for Visceral and Transplant Surgery Hannover Medical School

AIM To investigate the impact of hepatic encephalopathybefore orthotopic liver transplantation(OLT) and neurological complications after OLT on employment after OLT.METHODS One hundred and fourteen patients with chronic liver disease aged 18-60 years underwent neurological examination to identify neurological complications, neuropsychological tests comprising the pSE-SyndromeTest yielding the psychometric hepatic encephalopathy score, the critical flicker frequency and the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS), completed a questionnaire concerning their occupation and filled in the short form 36(SF-36) to assess health-related quality of life before OLT and 12 mo after OLT, if possible. Sixty-eight(59.6%) patients were recruited before OLT, while on the waiting list for OLT at Hannover Medical School [age: 48.7 ± 10.2 years, 45(66.2%) male], and 46(40.4%) patients were included directly after OLT. RESULTS Before OLT 43.0% of the patients were employed. The patients not employed before OLT were more often non-academics(employed: Academic/non-academic 16(34.0%)/31 vs not employed 10(17.6%)/52, p = 0.04), had more frequently a history of hepatic encephalopathy(HE)(yes/no; employed 15(30.6%)/34 vs not employed 32(49.2%)/33, p = 0.05) and achieved worse results in psychometric tests(RBANS sum score mean ± SD employed 472.1 ± 44.5 vs not employed 443.1 ± 56.7, p = 0.04) than those employed. Ten patients(18.2%), who were not employed before OLT, resumed work afterwards. The patients employed after OLT were younger [age median(range, min-max) employed 47(42, 18-60) vs not employed 50(31, 29-60), p = 0.01], achieved better results in the psychometric tests(RBANS sum score mean ± SD employed 490.7 ± 48.2 vs not employed 461.0 ± 54.5, p = 0.02) and had a higher health-related quality of life(SF 36 sum score mean ± SD employed 627.0 ± 138.1 vs not employed 433.7 ± 160.8; p pared to patients not employed after OLT. Employment before OLT(p p < 0.01) and SF-36 sum sc

关键词：肝的 encephalopathy 雇用神经病学的复杂并发症认知功能生活的健康相关的质量肝移植

Ribavirin in Acute Hepatitis E Infection in patients with Gynecological Cancer:A Case Series

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Journal of Clinical and Translational Hepatology 2018年第2期6卷 237-240页

作者： Dominik Bettinger Stefan Schlabe Sven pischke Michael R.Mallmann Mignon-Denise Keyver-paik Walther Kuhn christian p.strassburg Robert Thimme Ulrich Spengler Department of Medicine II Medical Center University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburgGermany Berta-Ottenstein-programme Faculty of MedicineUniversity of FreiburgFreiburgGermany Department of Internal Medicine I University of BonnBonnGermany Center for Integrated Oncology Cologne/Bonn BonnGermany Department of Medicine University Medical Center Hamburg-EppendorfHamburgGermany Department of Obstetrics and Gynecology University of BonnBonnGermany Department of Obstetrics and Gynecology University of CologneCologneGermany

Hepatitis E virus infection is usually a self-limited disease.However,during the last years there has been growing evidence for prolonged and chronic infection occurring in patients with immunosuppression.Also patients with malig-nant and rheumatic diseases have been identified to be at risk for chronic hepatitis E.However,their course and prognosis are not well characterized and there have been no reports of hepatitis E virus infection in patients with gynecological cancer.Here,we report three Caucasian females with breast and ovarian cancers presenting with elevation of amino-transferase levels during anticancer treatment.Although only few or no clinical hints suggested hepatitis E virus infection,the diagnosis of hepatitis E virus infection was confirmed by seroconversion,which might occur with some delay,and/or by polymerase chain reaction.While two patients had a self-limited course,the third patient with a high-risk oncological constellation required ribavirin in order to resume chemo-therapy.These cases highlight the need for hepatitis E virus testing in patients with gynecological cancer and elevated aminotransferase levels.Further,these cases show that in selected high-risk patients,ribavirin treatment may be nec-essary based on the decision of a multidisciplinary team.

关键词： Hepatitis E Gynecological cancer Liver function test Chemotherapy Immunosuppression

Between Scylla and Charybdis:The role of the human immune system in the pathogenesis of hepatitis C

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World Journal of Gastroenterology 2013年第44期19卷 7852-7866页

作者： Ulrich Spengler Hans Dieter Nischalke Jacob Nattermann christian p strassburg Department of Internal Medicine 1 University of Bonn 53105 Bonn Germany

Hepatitis C virus(HCV)frequently elicits only mild immune responses so that it can often establish chronic infection.In this case HCV antigens persist and continue to stimulate the immune system.Antigen persistence then leads to profound changes in the infected host’s immune responsiveness,and eventually contributes to the pathology of chronic hepatitis.This topic highlight summarizes changes associated with chronic hepatitis C concerning innate immunity(interferons,natural killer cells),adaptive immune responses(immunoglobulins,T cells,and mechanisms of immune regulation(regulatory T cells).Our overview clarifies that a strong anti-HCV immune response is frequently associated with acute severe tissue damage.In chronic hepatitis C,however,the effector arms of the immune system either become refractory to activation or take over regulatory functions.Taken together these changes in immunity may lead to persistent liver damage and cirrhosis.Consequently,effector arms of the immune system will not only be considered with respect to antiviral defence but also as pivotal mechanisms of inflammation,necrosis and progression to cirrhosis.Thus,avoiding Scylla-a strong,sustained antiviral immune response with inital tissue damage-takes the infected host to virus-triggered immunopathology,which ultimately leads to cirrhosis and liver cancerthe realm of Charybdis.

关键词： Natural killer cells CD4+T helper cells Regulatory T cells Interferon Hepatitis C Hepatic stellate cells Hepatocytes Immunoglobulin Retinoic acid inducible gene-Ⅰ Toll like receptors

Spontaneous bacterial peritonitis: The clinical challenge of a leaky gut and a cirrhotic liver

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World Journal of Hepatology 2015年第3期7卷 304-314页

作者： philipp Lutz Hans Dieter Nischalke christian p strassburg Ulrich Spengler Department of Internal Medicine I University of Bonn German Center for Infection Research

Spontaneous bacterial peritonitis(SBp) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. portal hypertension leads to increased bacterial translocation from the intestine. Failure to eliminate invading pathogens due to immune defects associated with advanced liver disease on the background of genetic predisposition may result in SBp. The efficacy of antibiotic treatment and prophylaxis has declined due to the spread of multi-resistant bacteria. patients with nosocomial SBp and with prior antibiotictreatment are at a particularly high risk for infection with resistant bacteria. Therefore, it is important to adapt empirical treatment to these risk factors and to the local resistance profile. Rifaximin, an oral, nonabsorbable antibiotic, has been proposed to prevent SBp, but may be useful only in a subset of patients. Since novel antibiotic classes are lacking, we have to develop prophylactic strategies which do not induce bacterial resistance. Farnesoid X receptor agonists may be a candidate, but so far, clinical studies are not available. New diagnostic tests which can be carried out quickly at the patient's site and provide additional prognostic information would be helpful. Furthermore, we need tools to predict antibiotic resistance in order to tailor first-line antibiotic treatment of spontaneous bacterial peritonitis to the individual patient and to reduce mortality.

关键词： Ascites Cirrhosis Farnesoid X receptor Liver Nucleotide-binding oligomerization domaincontaining 2 Rifaximin prophylaxis Spontaneousbacterial peritonitis Toll-like receptor 2

Changes of duplex parameters and splenic size in liver transplant recipients during a long period of observation

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World Journal of Gastroenterology 2005年第43期11卷 6787-6791页

作者： Bita Boozari Michael Gebel Mathias J Bahr Michael p Manns christian p strassburg Joerg S Bleck J Klempnauer Bjoern Nashan Department of Gastroenterology Department of Visceral and Transplant Surgery Department of Transplant Surgery

AIM: To assess the changes of portal and arterial velocities, resistance index, spleen and liver size during a long observation period (13.7 years) after orthotopic liver transplantation (OLT).METHODS: Two hundred and sixty patients were recruited retrospectively for this study and divided into groups with defined time intervals after OLT. The cross-sectional changes of portal and arterial velocities,resistance index, spleen and liver size between the defined time intervals were studied. The complications detected by ultrasound were compared to gold standard methods.RESULTS: The mean values for liver size were all within the normal range. The splenic size decreased between the time intervals 100 and 1 000 d after OLT (t;p＜0.01).While portal and arterial flow velocities decreased up to 5.5 years (t; portal velocity p＜0.01, maximal systolic velocity p=0.05, maximal end diastolic velocity p＜0.01),RI increased during this interval (t:p＜0.01). Higher RIvalues were found in older patients (r = 0.24, p＜0.001).CONCLUSION: The arterial and portal velocities show adaptation processes continuing over the course of many years after OLT and are reported for the first time. The vascular complications detected by ultrasound occur mostly up to 100 d after OLT.

关键词：肝移植脾疾病病理机制治疗

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胆汁淤积性肝病的诊治进展

胆汁淤积性肝病的诊治进展

Modern internet search analytics and thyroidectomy:What are patients asking?

第7届全国疑难及重症肝病大会

作者： christian p.strassburg Department of Internal Medicine I University of Bonn Germany

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 49-58页

作者： Neeraj Suresh christian Fritz Emma De Ravin Karthik Rajasekaran Department of Otorhinolaryngology–Head&Neck Surgery University of PennsylvaniaPhiladelphiaPennsylvaniaUSA perelman School of Medicine at the University of pennsylvania PhiladelphiaPennsylvaniaUSA Leonard Davis Institute of Health Economics University of PennsylvaniaPhiladelphiaPennsylvaniaUSA

Objectives:Thyroidectomy is among the most commonly performed head and neck surgeries,however,limited existing information is available on topics of interest and concern to patients.Study Design:Observational.Setting:Online.Methods:A search engine optimization tool was utilized to extract metadata on Google‐suggested questions that“people Also Ask”(pAA)pertaining to“thyroidectomy”and“thyroid surgery.”These questions were categorized by Rothwell criteria and topics of interest.The Journal of the American Medical Association(JAMA)benchmark criteria enabled quality assessment.Results:A total of 250 pAA questions were analyzed.Future‐oriented pAA questions describing what to expect during and after the surgery on topics such as postoperative management,risks or complications of surgery,and technical details were significantly less popular among the“thyroid surgery”group(pp=0.005,and ppectively).pAA questions about scarring and hypocalcemia were nearly threefold more popular than those related to pain(335 and 319 vs.113 combined search engine response page count,respectively).The overall JAMA quality score remained low(2.50±1.07),despite an increasing number of patients searching for“thyroidectomy”(r(77)=0.30,p=0.007).Conclusions:patients searching for the nonspecific term“thyroid surgery”received a curated collection of pAA questions that were significantly less likely to educate them on what to expect during and after surgery,as compared to patients with higher health literacy who search with the term“thyroidectomy.”This suggests that the content of pAA questions differs based on the presumed health literacy of the internet user.

关键词： information quality online health education search analytics thyroid surgery thyroidectomy

Efficient removal of the recalcitrant metamizole contaminant from drinking water by using a CaLaCoO_(9) perovskite supported on recycled polyethylene

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Journal of Environmental Sciences 2024年第2期136卷 56-67页

作者： Ernesto Valadez-Renteria christian perez-Carrasco Dulce Yolotzin Medina-Velazquez Vicente Rodriguez-Gonzalez Jorge Oliva CONACYT-División de Materiales Avanzados Instituto Potosino de Investigación Científica y Tecnológica A.C.San Luis PotosíSLP 78216México División de Ciencias Básicas e Ingeniería Universidad Autónoma Metropolitana AzcapotzalcoCol.Reynosa-TamaulipasC.P.MéxicoDF 02200México

Metamizole(MZ)is a widely used anti-inflammatory drug.Due to its common use,this contaminant is found in sewage and rivers.In order to reduce the contamination produced by the MZ,we fabricated in this work a photocatalytic composite using recycled polyethylene(RpE)and the CaLaCoO_(9)(LCCO)perovskite.Those nanoparticles had a microplate-like morphology and sizes of 1.4–5.5μm according to the analysis of microscopy.The photocatalytic properties of the LCCO powders were evaluated under ultraviolet-visible(UV-Vis)irradiation and found a removal efficiency of 96%.When the RpE+LCCO composite was employed for the photocatalytic degradation of MZ,a maximum degradation of 92.5%was obtained.The influence of the pH on the photocatalytic activity was also studied and found that an initial pH=3 produced a total degradation of MZ after 240 min of UV-Vis irradiation.Moreover,three reuse cycles were carried out for the pure LCCO powders and for the RpE+LCCO composites and found that the maximum loss of degradation was 5%.Furthermore,scavenger experiments demonstrated that the super oxide and hydroxyl radicals are formed during the photocatalytic reaction and were responsible for the degradation of MZ.Additionally,the X-ray photoelectron-spectroscopy and Raman analysis demonstrated the formation of defects(oxygen vacancies),those ones delayed the electron-hole recombination,which in turn,enhanced the degradation of the MZ.Thus,the studies performed in this work proved that composites made with recycled plastics and LCCO perovskites are a low-cost and feasible alternative for the cleaning of water sources polluted with pharmaceutical compounds.

关键词： photocatalysis Metamizole pharmaceutical contaminant UV-Vis irradiation perovskite