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Obeticholic acid for severe bile acid diarrhea with intestinal failure:A case report and review of the literature

World Journal of Gastroenterology 2018年第21期24卷 2320-2326页

作者： Christian Lodberg Hvas peter Ott peter Paine Simon Lal soren peter jorgensen Jens Frederik Dahlerup Department of Hepatology and Gastroenterology Aarhus University HospitalAarhus C 8000Denmark Department of Gastroenterology Salford Royal NHS Foundation TrustSalfordManchester M6 8HDUnited Kingdom

Bile acid diarrhea results from excessive amounts of bile acids entering the colon due to hepatic overexcretion of bile acids or bile acid malabsorption in the terminal ileum. The main therapies include bile acid sequestrants, such as colestyramine and colesevelam, which may be given in combination with the opioid receptor agonist loperamide. Some patients are refractory to conventional treatments. We report the use of the farnesoid X receptor agonist obeticholic acid in a patient with refractory bile acid diarrhea and subsequent intestinal failure. A 32-year-old woman with quiescent colonic Crohn's disease and a normal terminal ileum had been diagnosed with severe bile acid malabsorption and complained of watery diarrhea and fatigue. The diarrhea resulted in hypokalemia and sodium depletion that made her dependent on twice weekly intravenous fluid and electrolyte infusions. Conventional therapies with colestyramine, colesevelam, and loperamide had no effect. Second-line antisecretory therapies with pantoprazole, liraglutide, and octreotide also failed. Third-line treatment with obeticholic acid reduced the number of stools from an average of 13 to an average of 7 per 24h and improved the patient's quality of life. The fluid and electrolyte balances normalized. The effect was sustained during follow-up for 6 mo with treatment at a daily dosage of 25 mg. The diarrhea worsened shortly after cessation of obeticholic acid. This case report supports the initial report that obeticholic acid may reduce bile acid production and improve symptoms in patients with bile acid diarrhea.

关键词： Bile acid malabsorption Diarrhea Farnesoid X-activated receptor Crohn’s disease

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Metabolomic, Transcriptional, Hormonal, and Signaling Cross-Talk in Superroot2

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Molecular Plant 2010年第1期3卷 192-211页

作者： Marc Morant Claus Ekstrom peter Ulvskov Charlotte Kristensen Mats Rudemo Carl Erik Olsen Jorgen Hansen Kirsten jorgensena Bodil jorgensen Birger Lindberg Moilera soren Bak Plant Biochemistry Laboratory Department of Plant Biology and Biotechnology University of Copenhagen 40 Thorvaldsensvej DK-1871 FrederiksbergC Copenhagen Denmark Center for Molecular Plant Physiology University of Copenhagen. DK-1871 Frederiksberg C Copenhagen Denmark Department of Natural Sciences University of Copenhagen DK-1871 Frederiksberg C Copenhagen Denmark VKR research centre 'Pro-Active Plants' Plant Biochemistry Laboratory Department of Plant Biology and Biotechnology University of Copenhagen DK-1871 Frederiksberg C Copenhagen Denmark Evolva A/S Bulowsvej 25 DK-1870 Frederiksberg C Copenhagen Denmark Center for Applied Bioinformatics at LIFE University of Copenhagen 40 Thorvaldsensvej DK-1871 Frederiksberg C Copenhagen Denmark

Auxin homeostasis is pivotal for normal plant growth and development. The superroot2 （sur2） mutant was initially isolated in a forward genetic screen for auxin overproducers, and SUR2 was suggested to control auxin conju- gation and thereby regulate auxin homeostasis. However, the phenotype was not uniform and could not be described as a pure high auxin phenotype, indicating that knockout of CYP83B1 has multiple effects. Subsequently, SUR2 was identified as CYP83B1, a cytochrome P450 positioned at the metabolic branch point between auxin and indole glucosinolate metabolism. To investigate concomitant global alterations triggered by knockout of CYP83B1 and the countermeasures chosen by the mutant to cope with hormonal and metabolic imbalances, 10-day-old mutant seedlings were characterized with respect to their transcriptome and metabolome profiles. Here, we report a global analysis of the sur2 mutant by the use of a combined transcriptomic and metabolomic approach revealing pronounced effects on several metabolic grids including the intersection between secondary metabolism, cell wall turnover, hormone metabolism, and stress responses. Metabolic and transcriptional cross-talks in sur2 were found to be regulated by complex interactions between both positively and negatively acting transcription factors. The complex phenotype of sur2 may thus not only be assigned to elevated levels of auxin, but also to ethylene and abscisic acid responses as well as drought responses in the absence of a water deficiency. The delicate balance between these signals explains why minute changes in growth conditions may result in the non-uniform phenotype. The large phenotypic variation observed between and within the different surveys may be reconciled by the complex and intricate hormonal balances in sur2 seedlings decoded in this study.

关键词： Abiotic/environmental stress hormonal regulation metabolomics secondary metabolism/natural products transcriptome analysis development.

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The clinical impact of bacterial biofilms

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International Journal of Oral Science 2011年第2期3卷 55-65页

作者： Niels Hoiby Oana Ciofu Helle Krogh Johansen Zhi-jun Song Claus Moser peter Ostrup Jenser soren Molin Michael Givskov Tim Tolker-Nieisen Thomas Bjamsholt Department of Clinical Microbiology Rigshospitalet Institute for International Health Medical Microbiology and Immunology BloScience and Technology Biocentrum Danish Technical University

Bacteria survive in nature by forming biofilms on surfaces and probably most, if not all, bacteria （and fungi） are capable of forming biofilms. A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and extracellular DNA. Bacterial biofilms are resistant to antibiotics, disinfectant chemicals and to phagocytosis and other components of the innate and adaptive inflammatory defense system of the body. It is known, for example, that persistence of staphylococcal infections related to foreign bodies is due to biofilm formation. Likewise, chronic Pseudomonas aeruginosa lung infections in cystic fibrosis patients are caused by biofilm growing mucoid strains. Gradients of nutrients and oxygen exist from the top to the bottom of biofilms and the bacterial cells located in nutrient poor areas have decreased metabolic activity and increased doubling times. These more or less dormant cells are therefore responsible for some of the tolerance to antibiotics. Biofilm growth is associated with an increased level of mutations. Bacteria in biofilms communicate by means of molecules, which activates certain genes responsible for production of virulence factors and, to some extent, biofilm structure. This phenomenon is called quorum sensing and depends upon the concentration of the quorum sensing molecules in a certain niche, which depends on the number of the bacteria. Biofilms can be prevented by antibiotic prophylaxis or early aggressive antibiotic therapy and they can be treated by chronic suppressive antibiotic therapy. Promising strategies may include the use of compounds which can dissolve the biofilm matrix and quorum sensing inhibitors, which increases biofilm susceptibility to antibiotics and phagocytosis.

关键词： bacterial biofilm biofilm infection antibiotic resistance quorum sensing

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Bone mineral density in lifelong trained male football players compared with young and elderly untrained men

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Journal of Sport and Health Science 2018年第2期7卷 159-168页

作者： Marie Hagman Eva Wulff Helge Therese Hornstrup Bjorn Fristrup Jens Jung Nielsen Niklas Rye jorgensen Jesper Lovind Andersen Jorn Wulff Helge peter Krustrup Department of Sports Science and Clinical Biomechanics SDU Sport and Health Sciences Cluster (SHSC) University of Southern Denmark Odense 3450 Denmark Department of Nutrition Exercise and Sports University of Copenhagen Copenhagen N 2200 Denmark Institute of Sports Medicine Copenhagen Bispebjerg Hospital Copenhagen NV 2400 Denmark Department of Clinical Biochemistry Rigshospitalet Research Center for Ageing and Osteoporosis Glostrup 2600 Denmark Center of Healthy Aging Department of Biomedical Sciences University of Copenhagen Copenhagen N 2200 Denmark Sport and Health Sciences University of Exeter Exeter EX1 2LU UK

Purpose: The purpose of the present controlled cross-sectional study was to investigate proximal femur and whole-body bone mineral density(BMD), as well as bone turnover profile, in lifelong trained elderly male football players and young elite football players compared with untrained age-matched ***: One hundred and forty healthy, non-smoking men participated in the study, including lifelong trained football players(FTE, n = 35)aged 65—80 years, elite football players(FTY, n = 35) aged 18—30 years, as well as untrained age-matched elderly(UE, n = 35) and young(UY,n = 35) men. All participants underwent a regional dual-energy X-ray Absorptiometry(DXA) scan of the proximal femur and a whole-body DXA scan to determine BMD. From a resting blood sample, the bone turnover markers(BTMs) osteocalcin, carboxy-terminal type-1 collagen crosslinks(CTX-1), procollagen type-1 amino-terminal propeptide(P1NP), and sclerostin were ***: FTE had 7.3%—12.9% higher(p < 0.05) BMD of the femoral neck, wards, shaft, and total proximal femur in both legs compared to UE,and 9.3%—9.7% higher(p < 0.05) BMD in femoral trochanter in both legs compared to UY. FTY had 24.3%—37.4% higher(p < 0.001) BMD in all femoral regions and total proximal femur in both legs compared to UY. The whole-body DXA scan confirmed these results, with FTE showing similar whole-body BMD and 7.9% higher(p < 0.05) leg BMD compared to UY, and with FTY having 9.6% higher(p < 0.001) wholebody BMD and 18.2% higher(p < 0.001) leg BMD compared to UY. The plasma concentration of osteocalcin, CTX-1, and P1NP were 29%,53%, and 52% higher(p < 0.01), respectively, in FTY compared to ***: BMD of the proximal femur and whole-body BMD are markedly higher in lifelong trained male football players aged 65—80 years and young elite football players aged 18—30 years compared to age-matched untrained men. Elderly football players even show higher BMD in femoral trochanter and leg BMD than untrained young despi

关键词：物质密度运动员训练足球骨头 BMD 播放器 FTY

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Therapeutic improvement of colonic anastomotic healing under complicated conditions: A systematic review

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World Journal of Gastrointestinal Surgery 2016年第5期8卷 389-401页

作者： Malene Nerstrom peter-Martin Krarup Lars Nannestad jorgensen Magnus S Agren Digestive Disease Center Bispebjerg Hospital University of Copenhagen DK-2400 Copenhagen NV Denmark Copenhagen Wound Healing Center Bispebjerg Hospital University of Copenhagen DK-2400 Copenhagen NV Denmark Department of Clinical Medicine Faculty of Health and Medical Sciences University of CopenhagenDK-2200 Copenhagen Denmark

AIM: To identify therapeutic agents for the prophylaxis of gastrointestinal anastomotic leakage(AL) under complicated conditions. METHODS: The Pub Med and EMBASE databases were searched for English articles published between January 1975 and September 2014. Studies with the primary purpose of improving anastomotic healing in the colon or rectum under complicated preoperative and/or intraoperative conditions were included. We excluded studies investigating the adverse effects or risk assessment of an active intervention. Furthermore, investigations of biophysical materials, sealants, electrical stimulation and nutrients were excluded. The primary study outcome was biomechanical anastomotic strength or AL. The meta-analysis focused on therapeutic agents that were investigated in one animal model using the same outcome by at least three independent research groups. RESULTS: The 65 studies included were divided into 7 different complicated animal models: Bowel ischemia, ischemia/reperfusion, bowel obstruction, obstructive jaundice, peritonitis, chemotherapy and radiotherapy. In total, 48 different therapeutic compounds were examined. The majority of investigated agents(65%) were reported as beneficial for anastomotic healing. Twelve of the agents(25%) were tested more than once in the same model, whereas 13(27%) of the agents were tested in two or more models of complicated healing. Two therapeutic agents met our inclusion criteria for the meta-analysis. Postoperative hyperbaric oxygen therapy significantly increased anastomoticbursting pressure in ischemic colon anastomoses by a mean of 28 mm Hg(95%CI: 17 to 39 mm Hg, P < 0.00001). Granulocyte macrophage-colony stimulating factor failed to show a significant increase in anastomotic bursting pressure(95%CI:-20 to 21 mmH g, P = 0.97) vs controls in experimental chemotherapeutic models. CONCLUSION: This systematic review identified potential therapeutic agents, but more studies are needed before concluding that any of the

关键词： Anastomotic healing Colorectal surgery Breaking strength Bursting pressure Anastomotic leakage Ischemia Chemotherapy Reperfusion Bowel obstruction Peritonitis Radiotherapy

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丹麦风电的未来

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能源技术经济 2011年第3期23卷 6-10页

作者： peter jorgensen 丹麦电网公司

丹麦是世界风电行业的领跑者。介绍了丹麦大力发展风电的驱动力,描述了风电发展给电力行业以及人民生活带来的影响,阐述了风电的社会经济效益。详细论述了丹麦通过负荷经济调度、电力进出口以及上下调制电能产量从而实现了电力消费的20... 详细信息

丹麦是世界风电行业的领跑者。介绍了丹麦大力发展风电的驱动力,描述了风电发展给电力行业以及人民生活带来的影响,阐述了风电的社会经济效益。详细论述了丹麦通过负荷经济调度、电力进出口以及上下调制电能产量从而实现了电力消费的20%来自于风能。为实现欧盟的"20-20-20"目标,电网基础设施建设、灵活的生产与消费以及智能电网方案将为可再生能源尤其是风电的发展提供坚强的平台。负荷经济调度在新的方案下是实现社会经济效益最大化的有效措施。

关键词：风电能源消费智能电网社会经济效益负荷经济调度需求响应供需平衡

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Pharmacological interventions for improved colonic anastomotic healing:A meta-analysis

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World Journal of Gastroenterology 2014年第35期20卷 12637-12648页

作者： Mari Nanna φines peter-Martin Krarup Lars Nannestad jorgensen Magnus Sven Agren Digestive Disease Center Bispebjerg HospitalUniversity of Copenhagen Copenhagen Wound Healing Center Bispebjerg HospitalUniversity of Copenhagen Department of Clinical Medicine Faculty of Health and Medical SciencesUniversity of Copenhagen

AIM:To identify pharmaceuticals for the prophylaxis of anastomotic leakage(AL),we systematically reviewed studies on anastomosis repair after colorectal ***:We searched PubMed and EMBASE for articles published between January 1975 and December *** included studies in English with the primary purpose of promoting healing of anastomoses made in the colon or rectum under uncomplicated *** excluded studies on adverse events from interventions,nutritional interventions or in situ physical supporting *** primary outcome was biomechanical strength or *** performed meta-analyses on therapeutic agents investigated by three or more independent research groups using the same *** DerSimonian-Laird method for random effects was applied with P < ***:Of the 56 different therapeutic agents assessed,7 met our inclusion criteria for the *** prostacyclin analog iloprost increased the weighted mean of the early bursting pressure of colonic anastomoses in male rats by 60 mmHg(95%CI:30-89) vs the controls,and the immunosuppressant tacrolimus increased this value by 29 mmHg(95%CI:4-53) vs the *** showed an enhancement of bursting pressure by 45 mmHg(95%CI:14-76).The anabolic compound growth hormone augmented the anastomotic strength by 21 mmHg(95%CI:7-35),possibly via the up-regulation of insulin-like growth factor-1,as this growth factor increased the bursting pressure by 61 mmHg(95%CI:43-79) via increased collagen *** oxygen therapy increased the bursting pressure by 24 mmHg(95%CI:13-34).Broad-spectrum matrix metalloproteinase inhibitors increased the bursting pressure by 48 mmHg(95%CI:31-66) on postoperative days *** the only human study,the AL incidence was not significantly reduced in the 103 colorectal patients treated with aprotinin(11.7%) compared with the 113 placebo-treated patients(9.7%).CONCLUSION:This systematic review identified only one randomized clinical trial a

关键词： Anastomotic healing Colorectal surgery Ex-periment

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丹麦：风电占比50％不是童话

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能源评论 2012年第9期 66-69页

作者： peter·jorgensen[丹麦] 程红丹麦国家电网公司不详

要使风电入网并保证良好的电网运行，需要良好的电网和风电场建设规划、准确的风功率预测，在无风时要有充足的后备电源以及良性的电力市场。丹麦正是通过这些手段达到了20％的风电占比。

关键词：风电场建设丹麦童话电网运行功率预测电力市场后备电源

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地球上最大的龅牙

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小哥白尼（野生动物） 2010年第1期 40-43页

作者：刘海儿 Kristin Laidre Mads peter Heide-jorgensen

人类以龅牙为丑，动物却以龅牙为美!兔八哥的龅牙啃起萝卜真麻利，鼠小弟的龅牙就像小凿子：又快又锋利：海象那对长苌的龅牙可以撬开坚硬的贝壳，还能在冰面上爬行时当“拐杖……

关键词：《地球上最大的龅牙》刘海儿当代作品动物学

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A Modified Treatment Failure Classification System with Complete and Exhaustive Accounting of Any Adverse Events Related to the Previous Percutaneous Coronary Intervention

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World Journal of Cardiovascular Diseases 2014年第9期4卷 405-415页

作者： Anders MGalloe Jorgen LJeppesen soren Boesgaard John Godtfredsen Niels Bligaard Jens FLassen Henning Kelbaek Anders Junker Jan Ravkilde peter Riis Hansen Carsten TLarsen Ghita BStephansen Ulrik Abildgaard Department of Cardiology Copenhagen University HospitalRoskildeDenmark Department of Medicine Copenhagen University HospitalGlostrupDenmark Department of Cardiology Copenhagen University HospitalRigshospitaletDenmark Department of Cardiology Copenhagen University HospitalHerlevDenmark Department of Cardiology Copenhagen University HospitalGentofteDenmark Department of Cardiology Aarhus University HospitalSkejbyDenmark Department of Cardiology Odense University HospitalDenmark Department of Cardiology Aalborg University HospitalDenmark

Objectives: To determine the clinical outcome related to treatment failure of the percutaneous coronary intervention (PCI) itself. Background: When considering the addition of PCI to the medical treatment of angina, it is necessary to know the balance between the benefit and the risk of the PCI itself, but the latter remains unknown. The usual outcome measures are imprecise because they contain events unrelated to the previous PCI and because some events clearly caused by PCI treatment failures are omitted. Methods: In total, 2098 unselected patients were randomized to receive either sirolimus-(n = 1065) or paclitaxel-(n = 1033) eluting coronary stents and followed for five years in the SORT OUT II. Any death, cardiac death, myocardial infarction (MI), stent thrombosis and documented stenosis was classified and combined to a “patient oriented clinical outcome” (POCO), the classical “major adverse cardiac events” (MACE) and the new “PCI-treatment oriented clinical outcome” (TOCO). Results: POCO occurred in 746 patients (35.6%), MACE in 467 patients (22.3%) and TOCO in 293 patients (14.0%), thus TOCO amounted to 39% of the POCO and to 63% of the MACE. Conclusion: By introduction of the present PCI treatment failure classification system, the clinical outcome of PCI-treatment itself may be credulously estimated by the rate of TOCO and eventually PCI is substantially better than what might be perceived from the classically used POCO and MACE rates.

关键词： PCI Angina Clinical Outcome

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