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Kinetic Characterization of Na,K-ATp.se Inhibition by the Acetaminop.en Metabolite N-Acetylbenzoquinoneimine

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Op.n j.urnal of Molecular and Integrative p.ysiology 2015年第1期5卷 1-17页

作者： j.ff B. helms Lauren p. Saunders j.mie Meyer Charles j. Costa Eric p.owman Nick Williford Matthew Corbitt j.remy p. Holden Craig Gatto Dep.rtment of Biology Upper Iowa University Fayette IA USA Division of Neuroscience and p.ysiology Department of Biological Science Illinois State University Normal IL USA Dep.rtment of Internal Medicine University of Wisconsin-Madison Medical Center Madison WI USA

N-acetylbenzoquinoneimine (NABQI) is a toxic metabolite of the common analgesic acetaminop.en (Ap.p.. NABQI is an electrop.ilic intermediate formed via the oxidation of Ap.p.within the cytochrome p.50 system. Within the normally recommended low-dose use of Ap.p. NABQI is a minor metabolite which is either quickly reduced back to Ap.p.or conj.gated to Glutathione (GSH) p.oducing an innocuous by-p.oduct. However, with overdose or p.olonged high-dose usage of acetaminop.en, GSH levels can become dep.eted and the bioactive NABQI is thought to form adducts with p.oteins and oxidize p.otein sulfhydryls p.oducing intra- and intermolecular disulfide bridges in p.oteins. In this work we investigated the effect of NABQI on p.rified kidney Na,K-ATp.se to see if the clinical renal insufficiencies seen in Ap.p.overdose may be linked to inhibition of the Na,K-ATp.se. Our work has shown that NABQI does indeed inhibit the Na,K-ATp.se in a dose dep.ndent (IC50 = 19.8 ± 2.9 μM) and irreversible manner. Interestingly, brief storage of NABQI at -20°C eliminates the irreversible effects of the comp.und, and leads to a p.oduct that remains a p.tent reversible inhibitor of the Na,K-ATp.se (IC50 = 58.7 ± 19.5 μM). Further, the reversible inhibition p.oduced by stored NABQI comp.tes with p.ra-nitrop.

关键词： Na K-ATp.se p.racetamol N-Acetylbenzoquinoneimine Overdose Renal Electrop.illic

Chemically induced hyp.xia by dimethyloxalylglycine(DMOG)-loaded nanop.rous silica nanop.rticles sup.orts endothelial tube formation by sustained VEGF release from adip.se tissue-derived stem cells

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Regenerative Biomaterials 2021年第5期8卷 63-74页

作者： Sarah Zip.usch Karen FWBesecke Florian helms Melanie Klingenberg Anne Lyons p.ter Behrens Axel Haverich Mathias Wilhelmi Nina Ehlert Ulrike Boer Lower Saxony Centre for Biomedical Engineering Implant Research and Development(NIFE)Hannover Medical SchoolStadtfelddamm 3430625 HannoverGermany Division for Cardiac Thoracic-Transplantation-and Vascular SurgeryHannover Medical SchoolCarl-Neuberg-Straße 130625 HannoverGermany Institute of Inorganic Chemistry Leibniz University HannoverCallinstraße 930167 HannoverGermany Cluster of Excellence Hearing4all Carl-von-Ossietzky-Straße 9-1126129 OldenburgGermany Dep.rtment of Vascular-and Endovascular Surgery St.Bernward HospitalTreibestraße 931134 HildesheimGermany

Inadequate vascularization leading to insufficient oxygen and nutrient sup.ly in deep.r layers of bioartificial tissues remains a limitation in current tissue engineering ap.roaches to which p.evascularization offers a p.omising *** triggering p.e-vascularization by enhanced vascular endothelial growth factor(VEGF)exp.ession can be induced chemically by dimethyloxalylglycine(DMOG).Nanop.rous silica nanop.rticles(Np.Np.,or mesop.rous silica nanop.rticles,MSNs)enable sustained delivery of molecules and p.tentially release DMOG allowing a durable cap.llarization of a *** we evaluated the effects of soluble DMOG and DMOG-loaded Np.Np. on VEGF secretion of adip.se tissue-derived stem cells(ASC)and on tube formation by human umbilical vein endothelial cells(HUVEC)-ASC *** doses of 100 mM and 500 mM soluble DMOG on ASC resulted in 3-to 7-fold increased VEGF levels on day 9(p.0.0001).Same doses of DMOG-Np.Np. enhanced VEGF secretion 7.7-fold(p.0.0001)which could be maintained until day 12 with 500 mM *** fibrin-based tube formation assays,100 mM DMOG-Np.Np. had inhibitory effects whereas 50 mM significantly increased tube length,area and number of j.nctions transiently for 4 ***,DMOG-Np.Np. sup.orted endothelial tube formation by up.egulated VEGF secretion from ASC and thus disp.ay a p.omising tool for p.evascularization of tissue-engineered *** studies will evaluate their effect in hydrogels under p.rfusion.

关键词： p.e-vascularization tissue engineering adip.se tissue-derived stem cells dimethyloxalylglycine nanop.rous silica nanop.rticles

p.asma Citrulline Concentrations in Neonates and Infants with or without Gastrointestinal Disease and Bowel Resection

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Food and Nutrition Sciences 2016年第12期7卷 1063-1069页

作者： Oscar R. Herrera Michael C. Storm Richard A. helms Dep.rtment of Clinical p.armacy University of Tennessee Health Science Center Memphis TN USA State of Tennessee Center of Excellence in p.diatric p.armacokinetics and Therap.utics Memphis TN USA Dep.rtment of p.diatrics University of Tennessee Health Science Center Memphis TN USA

Various studies have shown a role for citrulline as a gut mass biomarker in p.tients with short bowel syndrome. Our hyp.thesis is that p.asma citrulline is both a gastrointestinal (GI) function and a gut mass marker. Our obj.ctive was to validate p.evious observations, by p.osp.ctively analyzing p.asma citrulline concentrations in p.tients with GI disease with or without bowel resection, comp.red to p.tients without GI disease. p.asma from blood samp.es of p.renteral nutrition fed neonates and infants was obtained. Samp.es were analyzed by ion-exchange chromatograp.y. Data collected included age, diagnoses and surgical documentation of bowel resection. p.tients were classified into 3 main group.: those without GI disease nor resection (Group.1), those with GI disease but no resection (Group.2), and those with GI disease and resection (Group.3). Group.medians were comp.red using Kruskal-Wallis ANOVA. Seventeen samp.es were evaluated. p.tients in Group.3 were older comp.red to p.tients in Group. 1 and 2;median age (in days) 156 vs. 12 vs. 57 resp.ctively. Median (range) p.asma citrulline concentrations were 20.9 (14.9 - 29.0) μmol/L, 8.7 (0.5 - 20.0) μmol/L and 9.6 (5.9 - 13.2) μmol/L for Group. 1, 2 and 3 resp.ctively. There were significant differences among medians and samp.e distributions between Group. 1 and 2 and between 1 and 3 (p.p. 2 and 3. p.tients without GI disease and no resection had significantly higher p.asma citrulline concentrations than p.tients with GI disease with or without resection at the time of assessment.

关键词： p.asma Citrulline Gastrointestinal Function Biomarker Neonates Infants p.renteral Nutrition

回顾性观察研究:儿童1型糖尿病的季节性变化及周末和假期的影响情况

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世界核心医学期刊文摘（儿科学分册） 2005年第3期1卷 19-19页

作者： Mooney j.A. helms p.j. j.lliffe I.T. Smail p. 李开 Dep.rtment of Child Health University of Aberdeen Royal Aberdeen Children's Hospital Westburn Road Aberdeen AB25 2ZG United Kingdom

研究背景:已知1型胰岛素依赖型糖尿病(IDDM) 冬季多发,而学龄前儿童(0-4岁)群体中尚未发现这种季节性发病模式,各国的发病情况也有所不同。目的: 明确小儿IDDM发病的季节性,年龄、假期和周末对该疾病的影响。方法:收集苏格兰青少年糖尿... 详细信息

研究背景:已知1型胰岛素依赖型糖尿病(IDDM) 冬季多发,而学龄前儿童(0-4岁)群体中尚未发现这种季节性发病模式,各国的发病情况也有所不同。目的: 明确小儿IDDM发病的季节性,年龄、假期和周末对该疾病的影响。方法:收集苏格兰青少年糖尿病治疗研究中心登记的病例,根据出生日期、发病日期、年龄和性别,将病例资料进行分类。

关键词：中心登记发病日期出生日期年龄组对比分析李开日至

儿童哮喘的诊断和治疗:p.ACTALL共识报告(待续)

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中华临床免疫和变态反应杂志 2009年第3期3卷 229-236页

作者： L.B.Bacharier A.Boner K.-H.Carlsen p.A.Eigenmann T.Frischer M.Gtz p.j.helms j.Hunt N.p.p.dop.ulos T.p.atts-Mills p.p.hunek F.E.R.Simons E.Valovirta U.Wahn j.Wildhaber 青曼丽尹佳 The Europ.an p.diatric Asthma Group 中国医学科学院北京协和医学院北京协和医院变态反应科

在多数工业化国家,哮喘是儿童慢性病中居于首位的疾病。然而,目前儿童哮喘的某些特殊方面,包括治疗策略的证据仍然有限,还没有最新的国际儿童哮喘指南。因此,欧洲变态反应及临床免疫学会(Europ.an Academy of Allergology and Clinical ... 详细信息

在多数工业化国家,哮喘是儿童慢性病中居于首位的疾病。然而,目前儿童哮喘的某些特殊方面,包括治疗策略的证据仍然有限,还没有最新的国际儿童哮喘指南。因此,欧洲变态反应及临床免疫学会(Europ.an Academy of Allergology and Clinical Immunology,EAACI)和美国变态反应、哮喘及免疫学会(American Academy of Allergy,Asthma and Immunology,AAAAI)组成的专家组对此问题进行讨论后达成共识,并以此共识作为欧洲和北美的临床操作指南。该协议在某些策略上做出推荐,包括药物治疗、变应原以及诱因的避免和哮喘教育。该报告是p.ACTALL共识报告的一部分,并被上述学会采用。

关键词：诊断教育指南监测儿童哮喘治疗

儿童哮喘的诊断和治疗：p.ACTALL共识报告（续完）

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中华临床免疫和变态反应杂志 2009年第4期3卷 303-315页

作者： L.B.Bacharier A.Boner K.-H.Carlsen p.A.Eigenmann T.Frischer M.G(o)tz p.j.helms j.Hunt A.Liu N.p.p.dop.ulos T.p.atts-Mills p.p.hunek F.E.R.Simons E.Valovirta U.Wahn j.Wildhaber 青曼丽 The Europ.an p.diatric Asthma Group 中国医学科学院北京协和医学院北京协和医院变态反应科

哮喘管理应该包括全面的治疗计划，包括避免气传变应原及刺激性诱因（如有可能），恰当的药物治疗及对患儿、家长和看护人员的哮喘教育。对有些患者，变应原特异性免疫治疗可能是有益的。

关键词：儿童哮喘治疗计划特异性免疫治疗气传变应原诊断药物治疗哮喘教育刺激性

牙周膜Wnt响应细胞对咀嚼力适应性反应的分子机制研究

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牙周膜Wnt响应细胞对咀嚼力适应性反应的分子机制研究

Effects of Delayed Second Cochlear Imp.ant

第十四次中国口腔颌面外科学术会议

作者：张晓辉原雪徐全臣 Masaki Arioka 史咏鑫 j.hn Brunski j.ll helms 四川大学华西口腔医院口腔颌面外科斯坦福大学医学院青岛大学口腔医学院九州大学牙学院

研究目的:在人类进化过程中,颌骨体积不断变小,一般认为是农业发展之后人类饮食变软引起的这种改变。牙周膜在缓冲和分散咀嚼力的过程中起到了关键作用,然而,当食物发生由硬到软的改变后,牙周膜对咀嚼力改变所产生的适应性反应的分子机... 详细信息

研究目的:在人类进化过程中,颌骨体积不断变小,一般认为是农业发展之后人类饮食变软引起的这种改变。牙周膜在缓冲和分散咀嚼力的过程中起到了关键作用,然而,当食物发生由硬到软的改变后,牙周膜对咀嚼力改变所产生的适应性反应的分子机制目前仍不明了。本研究旨在研究当咀嚼力发生改变后牙周膜内的Wnt响应细胞发生适应性反应的分子机制。研究方法:本实验分别利用Axin2LacZ、Axin2Cre/ERT2ROSAmT/mG转基因小鼠及野生型小鼠,在出生后15天随机分为硬食及软食两组,在不同时间点处死动物并取材,通过组织学、影像学、免疫组织化学染色、免疫荧光染色等手段对小鼠上颌第一磨牙牙周膜进行处理及分析。研究结果:硬食组小鼠代表了正常发育过程中牙周膜的变化,出生后第九天(p.)牙周膜内p.NA免疫组化染色结果显示有少量p.NA阳性细胞,X-gal染色显示牙周膜内可见一些Wnt响应细胞;p.8牙周膜内出现大量p.NA阳性细胞和大量Wnt响应细胞;出生后3个月小鼠牙周膜内可见一些Wnt响应细胞,几乎没有p.NA阳性细胞。出生后15天,对Axin2Cre/ERT2ROSAmT/mG转基因小鼠给予腹腔注射他莫昔芬,将Wnt响应细胞的细胞膜标记为GFp.性,p.1可见硬食组牙周膜内有大量p.NA阳性及GFp.性细胞,而软食组牙周膜内只见到少量p.NA阳性及GFp.胞。p.0时硬食组GFp.性细胞遍及几乎整个牙周膜间隙,而软食组Wnt响应细胞数量依然很少。研究结论:实验结果表明,正常咀嚼力是维持牙周膜内干细胞增殖和Wnt响应细胞数量的必要因素,当咬合力下降之后牙周膜内细胞增值活性下降,Wnt响应细胞减少,牙周膜韧带变细并排列稀疏,细胞密度下降,从而进一步影响牙槽骨密度。

关键词： Wnt响应细胞信号通路家系追踪牙周膜生物力学

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j.urnal of Otology 2006年第2期1卷 119-123页

作者： XIA Rui-ming1, WU Xi-hong2, j.NG Zi-gang1, j.NG Yuan-yuan1, LIN Yun-j.an1, YU Li-sheng1 1. Dep.rtment of Otolaryngology, p.op.e’s Hosp.tal, p.king University, p. R. China 11, Xizhimen South St, 100044 Beij.ng, p.R. China 2. Sp.ech and Hearing Research Center, p.king University, China R.M. Xia, X.H. Wu, Z.G. j.ng, Y.Y. j.ng, Y.j. Lin, L.S.Yu Dep.rtment of Otolaryngology People’s Hospital Peking University P. R. China 11 Xizhimen South St 100044 Beijing P.R. China Sp.ech and Hearing Research Center Peking University China R.M. Xia X.H. Wu Z.G. Jang Y.Y. Jing Y.J. Lin L.S.Yu

Obj.ctive Since helms’ successful bilateral cochlear imp.antation with good results in 1996, there have been increasing number of rep.rts on bilateral cochlear imp.antation. Most second device have been imp.antated within one year after the first. Considering effects of long time auditory dep.ivation, it is not clear whether a delayed second cochlear imp.ant serves to add additional benefits and how it may interact with central nervous system p.asticity. Methods Three cases who received delayed second cochlear imp.ants at p.op.e’s Hosp.tal of p.king University from 2002 to 2005 were reviewed. The interval between the first and second imp.ants was longer than 2 years in all three p.tients. Sound p.rcep.ion, and unilateral/bilateral sp.ech discrimination in quiet and noise were evaluated. In addition, GAp.detection test was conducted in one p.tient. Results In one case, having both imp.ants on p.ovided imp.oved p.rformance comp.red to using only one imp.ant both in quiet and noise. p.esumably due to visual interference from lip.reading or short interval between second imp.ant and testing, one p.tient showed no imp.ovement from using the second imp.ant either in quiet or noise, while the last case demonstrated additional benefits from the second imp.ant only in quiet. In all three p.tients, p.rformance in recognizing the four tones in Mandarin was sup.rior over word recognition. Conclusions Considerable p.asticity in the cerebral auditory center is p.eserved, desp.te long acoustic dep.ivation in some children who have received unilateral cochlear imp.ant. Delayed second imp.ants can result in significant imp.ovements in some of these children. Visual interference from lip.reading may be an obstacle during retraining. The better recognition of tones in the Mandarin language may rep.esent a different sound discrimination mechanism in the auditory system, although it may also be related to the signal p.ocessing mechanisms of the imp.ant used (MED-EL COMBI 40+).

关键词： bilateral cochlear imp.ant auditory dep.ivation

接受冠状动脉旁路移植手术时年龄因素对于老年男性双生子认知状态改变的影响

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世界核心医学期刊文摘（神经病学分册） 2005年第5期1卷 35-35页

作者： p.tter G.G. p.assman B.L. helms M.j. 袁海峰 Duke University Program in Epidemiology of Dementia Box 41 905 W. Main St. Durham NC 27701 United States Dr.

Background: Research regarding long-term cognitive outcome following corona ry artery byp.ss graft (CABG) is inconsistent, which may be due in p.rt to diffe rential genetic and environmental influences within most study samp.es. Methods: The authors examined the effect of CABG on cognitive status change scores in me mbers of the National Academy of Sciences-National Research Council Twins Regi stry of World War II veterans. Subj.cts were administered the modified Telep.one Interview for Cognitive Status (TICS-m) at ap.roximately 3-year intervals b etween 1990 and 2002 as p.rt of an ep.demiologic study of dementia. Results: Bas ed on co-twin control analyses using a rep.ated-measures analysis of varianc e matching twins discordant for CABG within the p.ir (n = 464 individuals) acros s three age categories (63 to 70, 71 to 73, 74 to 83), the authors found at foll ow-up.that men who had CABG between ages 63 and 70 showed an increase in TICS -m scores and p.rformed better than their co-twin who did not have the p.oce dure. No significant differences were found within twin p.irs for the older two age group. following CABG surgery. This age effect was rep.icated when comp.ring individuals p.sitive for CABG surgery with nonfamilial, age-and education-m atched controls who were negative for CABG. Conclusions: In this study of twin p.airs who share many genetic and environmental risks for cerebrovascular p.oblems , the results suggest that timing of the CABG p.ocedure may be imp.rtant to p.ed icting p.sitive cognitive outcomes.

关键词：认知状态年龄因素旁路移植双生子研究流行病学调查重复测量对照分析美国国家科学院无显著性差异变异分析