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Enhanced Free Radical Scavenging and Inhibition of DPP-4 and ACE Activities by Compounds from Salmon Tissues Digested in Vitro with Gastrointestinal Proteases

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Journal of Agricultural Science and Technology(B) 2014年第5期4卷 393-406页

作者： Susan Skanderup Falkenberg Jan Stagsted henrik hauch nielsen National Food Institute Technical University of Denmark Kgs. Lyngby DK-2800 Denmark Department of Food Science Aarhus University Tjele DK-8830 Denmark

Research on marine bioactive peptides has mainly focused on characterization of peptides in hydrolysates prepared with commercial industrial enzymes and the usefulness of such hydrolysates in health and functional foods. However, a relevant question is whether digestion of fish proteins with gastrointestinal proteases per se generates peptides that also can have health promoting properties and can reduce, e.g., diabetes 2, inflammation and hypertension either in relation to gastrointestinal digestion or as alternative to industrial proteases. The aim of the study was to investigate hydrolysates obtained from in vitro sequential digestion of salmon muscle and skin with gastrointestinal proteases including pepsin, pancreatic and pancreatic ＋ mucosal proteases for their ability to scavenge ABTS^＋ radicals and inhibit activity of angiotensin I-converting enzyme （ACE） and dipeptidyl peptidase 4 （DPP-4）. Furthermore, it was the aim to study the inhibitory mechanism and stability towards ACE and DPP-4 activity. Analysis of〈 10 kDa hydrolysates showed that gastrointestinal proteases generated peptides with clear radical scavenging activity and DPP-4 and ACE inhibiting activity as well. Hydrolysates from pepsin digestion exhibited the lowest ECso values for radical scavenging activity and ACE inhibition, whereas ECso increased in hydrolysates after subsequent digestion with pancreatic and mucosal proteases. Interestingly, ECso values for the DPP-4 inhibition were hardly affected by sequential digestion. Inhibition modes for the muscle hydrolysates were both competitive and non-competitive, but prolonged incubation showed that the inhibitory properties were unstable and therefore they were probably digested as competitive substrates by gastrointestinal proteases.

关键词： Salmon bioactive components ACE DPP-4 radical scavenging in vitro digestion gastrointestinal proteases.

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Effect of Gastrointestinal Protease Digestion on Bioactivity of Marine Peptides

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Journal of Agricultural Science and Technology(B) 2014年第1期4卷 74-84页

作者： Ida-Johanne Jensen Lisa Lystbek Andersen Carlo Gunnar Ossum Greta Jakobsen Cristian De Gobba Sabeena Farvin Koduvayur Habeebullah Inez Johansson Else Hoffmann Edel Oddny Elvevoll Flemming Jessen henrik hauch nielsen Faculty of Bioscience Fisheries and Economics Norwegian College of FisheO Science UniversiO of Tromso Tromso 9037Norway Division ofIndustrial Food Research National Food Institute DTU-Food Technical University qf Denmark Lyngby DK-2800Denmark Department of Biology Cell and Developmental Biology Universitv of Copenhagen Copenhagen 2100 Denmark Marinova ApS Adelvej 11 Lem St. 6940 Denmark Department of Food Science University o[Copenhagen Frederiksberg C 1958 Denmark

Focus in nutritional science has turned towards components in, or added to, foods that may possess health beneficial activities beyond the classical nutritional value, namely functional food. Bioactive peptides are examples of such components. In vitro studies on bioactivities have mainly been executed without concerning subsequent digestion after intake and the aim of this work was hence to investigate how the in vitro antioxidative, antihypertensive and caspase activating activities of peptides are affected by digestion with gastrointestinal （GI） proteases. Five different fish protein hydrolysates were chosen to study the effect of in vitro digestion on bioactivity. The protein concentration decreased in all samples during digestion and the molecular weight distribution of the peptides shifted towards lower values. Thus, in vitro digestion with GI proteases resulted in a further degradation of the peptides obtained by hydrolysis. The antihypertensive effect increased in all samples after digestion with GI proteases whereas the antioxidative capacity decreased. The effect on the caspase activity depended on the proteases used in the preparation of hydrolysates. In conclusion, the caspase activity and antihypertensive activity are maintained during digestion with GI proteases, while the antioxidative capacity seems to be reduced.

关键词： Antioxidative ACE in vitro caspase bioactivity marine peptides.

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Effects of a novel bacterial phytase expressed in Aspergillus Oryzae on digestibility of calcium and phosphorus in diets fed to weanling or growing pigs

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Journal of Animal Science and Biotechnology 2013年第2期4卷 102-111页

作者： Ferdinando nielsen Almeida Rommel Casilda Sulabo Hans henrik Stein Department of Animal Sciences University of Illinois

In 2 experiments, 48 weanling （initial BW： 13.5 ± 2.4 kg, Exp. 1） were used to determine effects of a novel bacterial 6-phytase and 24 growing pigs （initial BW： 36.2 ± 4.0 kg, Exp. 2） expressed in Aspergillus oryzae on the apparent total tract digestibility （ATTD） of phosphorus and calcium in corn-soybean meal diets fed to weanling and growing pigs. In Exp. 1 and 2, pigs were randomly allotted to 6 dietary treatments using a randomized complete block design and a balanced 2 period changeover design, respectively. In both experiments, 6 diets were formulated. The positive control diet was a corn-soybean meal diet with added inorganic phosphorus （Exp. 1：0.42 and 0.86% standardized total tract digestible phosphorus and total calcium, respectively; Exp. 2：0.32 and 0.79% standardized total tract digestible phosphorus and total calcium, respectively）. A negative control diet and 4 diets with the novel phytase （Ronozyme HiPhos, DSM Nutritional Products Inc., Parsippany, N J） added to the negative control diet at levels of 500, 1,000, 2,000, and 4,000 phytase units （FYT）/kg were also formulated. In Exp. 1, the ATTD of phosphorus was greater （P 〈 0.01） for the positive control diet （60.5%） than for the negative control diet （40.5%）, but increased （linear and quadratic, P 〈 0.01） as phytase was added to the negative control diet （40.5% vs. 61.6%, 65.1%, 68.7%, and 68.0%）. The breakpoint for the ATTD of phosphorus （68.4%） was reached at a phytase inclusion level of 1,016 FYT/kg. In Exp. 2, the ATTD of phosphorus was greater （P〈 0.01） for the positive control diet （59.4%） than for the negative control diet （39.8%） and increased （linear and quadratic, P〈 0.01） as phytase was added to the negative control diet （39.8% vs. 58.1%, 65.4%, 69.1%, and 72.8%）. The breakpoint for the ATTD of phosphorus （69.1%） was reached at a phytase inclusion level of 801 FYT/kg. in conclusion, the novel bacterial 6-phytase improved the ATTD of phosphorus and calcium in both weanling and growing pigs.

关键词： Calcium Digestibility Phosphorus Phytase Pigs

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Severe steroid refractory gastritis induced by Nivolumab: A case report

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World Journal of Gastroenterology 2020年第16期26卷 1971-1978页

作者： Helene Hjorth Vindum JØrgen S Agnholt Anders Winther Moelby nielsen Mette Bak nielsen henrik Schmidt Department of Oncology Aarhus University HospitalAarhus 8200Denmark Department of Gastroenterology Aarhus University HospitalAarhus 8200Denmark Department of Pathology Aarhus University HospitalAarhus 8200Denmark

BACKGROUND Immune checkpoint inhibitors are widely used for treatment of many advanced *** gastrointestinal(GI)side effects,such as diarrhea and colitis,are common,but upper GI side effects are rarely ***,the correct treatment of upper GI adverse events has been less frequently *** SUMMARY We describe a case of a 16-year-old woman with stage IIIb malignant melanoma treated with adjuvant monotherapy using *** patient developed severe gastritis after six series of Nivolumab with weight loss,nausea,and *** was no effect of intravenous steroids,but the patient′s condition resolved after administration of *** This case report supports the same treatment for gastritis as for colitis,which is in line with current guidelines.

关键词： Gastritis Immune checkpoint inhibitors Nivolumab Case report Immune-related adverse events Infliximab

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Amino acid digestibility of heat damaged distillers dried grains with solubles fed to pigs

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Journal of Animal Science and Biotechnology 2014年第1期5卷 88-97页

作者： Ferdinando nielsen Almeida John Kyaw Htoo John Thomson Hans henrik Stein Department of Animal Sciences University of Illinois1207 W Gregory DrUrbana IL 61801 USA Evonik Industries AG Rodenbacher Chaussee 4Hanau 63457 Germany Evonik Degussa Corporation 1701 Barrett LakesBlvd NW Kennesaw GA 30144 USA

The primary objective of this experiment was to determine the effects of heat treatment on the standardized ileal digestibility （SID） of amino acids （AA） in corn distillers dried grains with solubles （DDGS） fed to growing pigs. The second objective was to develop regression equations that may be used to predict the concentration of SID AA in corn DDGS. A source of corn DDGS was divided into 4 batches that were either not autoclaved or autoclaved at 130℃ for 10, 20, or 30 min. Four diets containing DDGS from each of the 4 batches were formulated with DDGS being the only source of AA and CP in the diets. A N-free diet also was formulated and used to determine the basal endogenous losses of CP and AA. Ten growing pigs （initial BW： 53.5 ＋ 3.9 kg） were surgically equipped with a T-cannula in the distal ileum and allotted to a replicated 5 x4 Youden square design with 5 diets and 4 periods in each square. The SID of CP decreased linearly （P〈 0.05） from 77.9% in non-autoclaved DDGS to 72.1, 66.1, and 68.5% in the DDGS samples that were autoclaved for 10, 20, or 30 min, respectively. The SID of lysine was quadratically reduced （P〈 0.05） from 66.8% in the non-autoclaved DDGS to 54.9, 55.3, and 51.9% in the DDGS autoclaved for 10, 20, or 30 min, respectively. The concentrations of SID Arginine, Histidine, Leucine, Lysine, Methionine, Phenylalanine, or Threonine may be best predicted by equations that include the concentration of acid detergent insoluble N in the model （r2 = 0.76, 0.68, 0.67, 0.84, 0.76, 0.73, or 0.54, respectively）. The concentrations of SID Isoleucine and Valine were predicted （r2 = 0.58 and 0.54, respectively） by the Lysine：CP ratio, whereas the concentration of SID Tryptophan was predicted （r2 = 0.70） by the analyzed concentration of Tryptophan in DDGS. In conclusion, the SID of AA is decreased as a result of heat damage and the concentration of SID AA in heat-damaged DDGS may be predicted by regression equations developed in this experiment.

关键词： Amino acids Digestibility Distillers dried grains with solubles Heat damage

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ALBERTSLUND LIBRARY,DENMARK:OPTIMIZATION OF INDOOR DAYLIGHT AND THERMAL CLIMATE CONDITIONS AND USE OF FAN-ASSISTED NATURAL VENTILATION IN A PUBLIC LIBRARY

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Journal of Green Building 2006年第4期1卷 3-10页

作者： Bruno nielsen henrik Sørensen Rasmus Pedersen Frans Drewniak Esbensen Consulting Vesterbrogade 124 BDK-1620 Copenhagen VDenmark Henning Larsens Tegnestue Vesterbrogade 76DK-1620 Copenhagen VDenmark

INTRODUCTION The theme for the renovation of Albertslund Library has been to create a markedly bright library that is open to its surroundings and *** overall objective is to satisfy the needs of the staff at the library and users in all age groups and from all social ***,the goal is to have a building which is optimized in terms of indoor daylight and thermal conditions,use of natural ventilation for saving energy in terms of cooling,and electricity for fan assistance and artificial light.

关键词： satisfy stratum library

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Early clinical outcome and learning curve following unilateral primary total knee arthroplasty after introduction of a novel total knee arthroplasty system

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World Journal of Orthopedics 2020年第10期11卷 431-441页

作者： Adam Omari Anders Troelsen henrik Husted Christian Skovgaard nielsen Kirill Gromov Department of Orthopedic Surgery Copenhagen University Hvidovre HospitalCopenhagen 2650Denmark Department of Orthopedic Surgery Copenhagen University Hospital HvidovreCopenhagen 2650Denmark

BACKGROUND New implants for total knee arthroplasty(TKA)are continuously introduced with the proposed benefit of increased performance and improved *** information exists on how the introduction of a novel arthroplasty implant affects the perioperative and surgical outcome immediately after *** To investigate how surgery-related factors and implant positioning were affected by the introduction of a novel TKA *** A novel TKA system was introduced at our institution on 30th November ***-five TKAs performed with the Persona TKA immediately following its introduction by 3 different surgeons(25 TKAs/surgeon)were identified as the Introduction ***,the latest 25 TKAs performed by each surgeon prior to introduction of the Persona TKA were identified as the Control Group.A Follow-up Group of 25 TKAs/surgeon was identified starting 1-year after the end of the introduction ***,surgery-related factors and alignment data were recorded,and intergroup differences *** Following introduction of the novel implant,Persona TKA was utilized in 69%(71%),53%(54%),and 45%(75%)of primary TKA procedures by the three surgeons,respectively(Follow-up Group).Mean surgery time was increased by 28%(P<0.0001)and mean intra-operative blood loss by 25%(P=0.002)in the Introduction Group,while only the mean surgery time was increased in the Follow-up Group by 18%(P<0.0001).Overall alignment was similar between the groups apart from femoral flexion(FF)and tibial slope(TS).The number of FF outliers was reduced in the Introduction Group with a more pronounced decrease in the Follow-up *** Introduction of the new TKA implant increased surgical time and intraoperative blood loss immediately after its *** differences diminished one year after introduction of the new *** outliers with respect to FF and TS were seen when using the novel TKA *** studies are needed to investigat

关键词： Total knee arthroplasty Early outcome Novel introduction Implant positioning Knee Component choice

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Amino acid digestibility in low-fat distillers dried grains with solubles fed to growing pigs

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Journal of Animal Science and Biotechnology 2014年第4期5卷 414-420页

作者： Shelby Marie Curry Diego Mario David Labadan Navarro Ferdinando nielsen Almeida Juliana Abranches Soares Almeida Hans henrik Stein Department of Animal Sciences University of Illinois

The objective of this experiment was to determine the standardized ileal digestibility（SID） of amino acids（AA） in 3sources of distillers dried grains with solubles（DDGS） with different concentrations of *** growing barrows（initial body weight：76.1 ± 6.2 kg） were randomly allotted to a replicated 6×4 Youden square design with 6 diets and 4 *** fat content of the 3 sources of DDGS were 11.5,7.5,and 6.9%*** contained 60%DDGS and fat concentration of the diets were 7.5,52,and 5.2%,*** additional diets containing the 2sources of DDGS with 75 and 6.9%fat were also formulated,and corn oil was added to these diets to increase the concentration of fat in the diets to levels that were calculated to be similar to the diet containing conventional DDGS with 11.5%fat.A N-free diet was also formulated to calculate endogenous losses of crude protein（CP） and AA from the *** were fed experimental diets during four 7-d *** first 5 d of each period were an adaptation period and ileal digesta were collected on d 6 and 7 of each *** apparent ileal digestibililty（AID） and SID of CP and all indispensable AA,except AID Pro and SID of Trp,were greater（P 〈 0.01） in conventional DDGS than in the 2 sources of DDGS with reduced *** oil to the diets containing the 2 sources of DDGS with reduced fat did not consistently increase SID of *** conclusion,conventional DDGS has greater SID values for most AA compared with DDGS that contains less fat and inclusion of additional oil to diets containing low-fat DDGS does not increase AID or SID of *** lower AA digestibility in low-fat DDGS could not be overcome by the inclusion of additional fat to the diets.

关键词： Amino acid digestibility Distillers dried grains with solubles Pigs

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Comparison of a New Magnetic Resonance Imaging Protocol and Magnetic Resonance Follow-Through in Patients with Inflammatory Bowel Disease—A Prospective Pilot Study

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Open Journal of Radiology 2015年第2期5卷 117-124页

作者： Kayalvily Jesuratnam-nielsen Vibeke B.Logager Pia Munkholm Yousef W.nielsen henrik S.Thomsen Department of Diagnostic Radiology Copenhagen University Hospital HerlevHerlevDenmark Faculty of Medical and Health Sciences University of CopenhagenCopenhagenDenmark DEEP—Danish Centre for eHealth&Epidemiology North Zealand HospitalFrederikssundDenmark

Objective: Inflammatory bowel disease (IBD) is a chronic disease, consisting of two main subgroups: Crohn’s disease (CD) and ulcerative colitis (UC). Imaging is an essential component in the treatment of IBD and is used repeatedly to determine activity and severity of inflammatory lesions. The aim of our study was to prospectively obtain pilot data on the accuracy of magnetic resonance imaging with no oral contrast (MRI-NOC) and magnetic resonance follow-through (MRFT) using endoscopy as the reference standard. Materials and Methods: Patients diagnosed with CD and UC referred to magnetic resonance imaging (MRI) were included in this study population. For the evaluation, the bowel was divided into 9 segments. Two radiologists, blinded to clinical findings, evaluated bowel wall thickness, diffusion weighted imaging and mural hyperenhancement. Results: 14 patients (9 males and 5 females;median age 41;range 20 - 62) underwent both type of MRI examinations;9 had CD and 5 had UC. The overall sensitivity for small bowel was zero for both MRI protocols, as neither identified any lesions, whereas in colon the sensitivity ranged from 7% to 29% in MRI-NOC and 14% - 29% in MRFT. Specificity and accuracy in MRI-NOC ranged from 78% to 98% and 74% - 93%, respectively, in small bowel, and from 90% to 96% and 77% - 82%, respectively, in colon. Specificity and accuracy in MRFT ranged from 83% to 100% and 79% - 95%, respectively, in small bowel, while it ranged from 93% to 97% and 81% - 85%, respectively, in colon. Conclusion: The location of lesions in the colon combined with the lack of oral contrast in the colon renders MRFT and MRI-NOC functionally identical.

关键词： Crohn’s Disease Faecal Calprotectin Inflammatory Bowel Disease Magnetic Resonance Imaging Ulcerative Colitis

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Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source

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World Journal of Gastroenterology 2019年第33期25卷 4904-4920页

作者： Michelle L Boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane Jens Christian nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang James L Trevaskis henrik H Hansen Cardiovascular Renal and Metabolic DiseasesMedImmuneGaithersburgMD 20878United States Pharmacology GubraH■rsholm DK-2970Denmark

BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of *** to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J *** To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated *** Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 *** and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)*** The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose ***-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same *** Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments.

关键词： Non-alcoholic steatohepatitis High-fat diet Mouse model Histopathology Fibrosis Liver biopsy Liver transcriptome

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