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舒马曲坦鼻腔喷雾治疗青少年偏头痛患者:一项随机、双盲、安慰剂对照的急性期研究

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世界核心医学期刊文摘（神经病学分册） 2006年第9期2卷 47-48页

作者： Winner p. Rothner A. D. Wooten j. D. 张慧(译) palm Beach Headache Center 4631 N. Congress Avenue West Palm Beach FL 33407 United States 不详

Obj.ctive. -To compare the efficacy and tolerability of sumatriptan nasal spray (ns) (5, 20 mg) versus placebo in the acute treatment of migraine in adolescent subj.cts. Background. -Currently, no triptan is approved in the United States for the treatment of migraine in adolescent subj.cts (12 to 17 years). In a previous randomized, placebo-controlled study of 510 adolescent subj.cts, sumatriptan ns at 5, 10, and 20 mg doses was well tolerated. However, the primary efficacy analysis for headache relief with 20 mg at 2 hours did not demonstrate statistical significance (p= .059). A second study was initiated to evaluate the efficacy of sumatriptan ns in this population. Methods. -This was a randomized (1:1:1), placebo-controlled, doubleblind, parallel-group study. Overall, 738 adolescent subj.cts (mean age: 14 years) with ≥6-month history of migraine (with or without aura) self-treated a single attack of moderate or severe migraine. The primary endpoints were headache relief at 1 hour and sustained relief from 1 to 24 hours. pain-free rates, presence/absence of associated symptoms, headache recurrence, and use of rescue medications were also assessed. Tolerability was based on adverse events (AEs) and vital signs. Results. -Sumatriptan ns 20 mg provided greater headache relief than placebo at 30 minutes (42%vs. 33%, respectively; p= .046) and 2 hours (68%vs. 58%; p= .025) postdose, but did not reach statistical significance at 1 hour (61%vs. 52%; p= .087) or for sustained headache relief from 1 to 24 hours (p= .061). Significant differences (p ptan ns 20 mg over placebo were observed for several secondary efficacy endpoints including sustained relief from 2 to 24 hours. In general, sumatriptan ns 5 mg percentages were slightly higher than placebo but the differences did not reach statistical significance. Both doses of sumatriptan ns were well tolerated. No AEs were serious or led to study withdrawal. The most common event was taste disturba

关键词：偏头痛患者鼻腔喷雾治疗安慰剂对照青少年患者舒马曲坦急性期治疗随机双盲

Mending the broken in amyotrophic lateral sclerosis: DNA damage and repair in motor neuron degeneration

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Neural Regeneration Research 2021年第1期16卷 104-105页

作者： Byung Woo Kim Lee j.Martin Department of pathology Division of Neuropathologythe Pathobiology Graduate Training ProgramJohns Hopkins University School of MedicineBaltimoreMDUSA Department of Neuroscience Johns Hopkins University School of MedicineBaltimoreMDUSA

Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disease that causes paralysis and respiratory failure(petrov et al.,2017).The driving mechanisms are unknown,and there are no effective treatments(petrov et al.,2017).Aging and a few gene mutations,a common one being missense mutations in superoxide dismutase-1(SOD1),are risk factors for ALS(Figure 1).The recent Food and Drug Administration approval of edaravone for the treatment of ALS putatively supports a role for oxidative and nitrative stresses in the disease processes(Figure 1A).DNA damage,abnormalities in DNA repair,and other nuclear abnormalities are implicated also in the pathogenesis of human ALS(Bradley and Krasin,1982;Kim et al.,2020).

关键词： al. damage degeneration

Better together? Treating traumatic brain inj.ry with minocycline plus N-acetylcysteine

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Neural Regeneration Research 2022年第12期17卷 2589-2592页

作者： Siobhán Lawless peter j.Bergold Graduate program in Neural and Behavioral Sciences State University of New York-Downstate Health Sciences UniversityBrooklynNYUSA Department of physiology and pharmacology State University of New York-Downstate Health Sciences UniversityBrooklynNYUSA

Traumatic brain inj.ry has a complex pathophysiology that produces both rapid and delayed brain damage. Rapid damage initiates immediately after inj.ry. Treatment of traumatic brain inj.ry is typically delayed many hours, thus only delayed damage can be targeted with drugs. Delayed traumatic brain inj.ry includes neuroinflammation, oxidative damage, apoptosis, and glutamate toxicity. Both the speed and complexity of traumatic brain inj.ry pathophysiology present large obstacles to drug development. Repurposing of Food and Drug Administration-approved drugs may be a highly efficient approach to get therapeutics to the clinic. This review examines the preclinical outcomes of minocycline and N-acetylcysteine as individual drugs and compares them to the minocycline plus N-acetylcysteine combination. Both minocycline and N-acetylcysteine are Food and Drug Administration-approved drugs with pleiotropic therapeutic effects. As individual drugs, minocycline and N-acetylcysteine are well tolerated, with known pharmacokinetics, and enter the brain through an intact blood-brain barrier. At concentrations greater than needed for antimicrobial action, minocycline is a potent anti-inflammatory minocycline, also acts as an antioxidant and inhibits multiple enzymes that promote brain inj.ry including metalloproteases, caspases, and polyADp-ribose-polymerase-1. N-acetylcysteine alone is also an antioxidant. It increases brain glutathione, prevents lipid oxidation, and protects mitochondria. N-acetylcysteine also acts as an anti-inflammatory as well as increases extracellular glutamate by activating the X;cystine-glutamate antitransporter. These multiple actions of minocycline and N-acetylcysteine have made them attractive candidates to treat traumatic brain inj.ry. When first dosed within the one hour after inj.ry, either minocycline or N-acetylcysteine improves a diverse set of therapeutic outcome measures in multiple traumatic brain inj.ry animal models. A small number of clinical

关键词： clinical trial outcome measures preclinical testing rodent models of traumatic brain inj.ry therapeutic time window

Fruit pomacesdtheir nutrient and bioactive components,effects on growth and health of poultry species,and possible optimization techniques

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Animal Nutrition 2022年第2期9卷 357-377页

作者： Taiwo j.Erinle Deborah I.Adewole Department of Animal Science and Aquaculture Faculty of AgricultureDalhousie UniversityTruroNS B2N 5E3 Canada

The ever-growing human population,coupled with the exigent need to meet the increasing demand for poultry meat and egg,has put the onus on poultry nutritionists and farmers to identify alternative feed ingredients that could assure the least-cost feed *** addition,the public desire for nonantibiotic-treated poultry products has also necessitated the ultimate search for potent antibiotic alternatives for use in poultry *** some identified alternatives are promising,their cost implications and technical know-how requirements may discourage their ease of adoption in *** use of plants and/or their by-products,like fruit pomaces,present a pocket-friendly advantage and as a result,are gaining much *** is traceable to their rich phytochemical profile,nutritional composition,ready availability,and relatively cheap *** fruit j.ice and wine pressing industries generate a plethora of fruit wastes ***,fruit pomaces contain appreciable dietary fibre,protein,and phenolic compounds,and thus,their adoption could serve the poultry industry in dual capacities including as substitutes to antibiotics and some conventional ***,there is a possibility to reduce fruit wastes produced and feed-cost in poultry farming from environmental and economical standpoints,*** review seeks to provide reinforcing evidence on the applicability and impact of fruit pomaces in poultry nutrition.

关键词： Fruit pomaces Antioxidant Growth performance Gut health poultry

Localised solid-state nanopore fabrication via controlled breakdown using on-chip electrodes

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Nano Research 2022年第11期15卷 9881-9889页

作者： j.sper p.Fried j.cob L.Swett Binoy paulose Nadappuram Aleksandra Fedosyuk Alex Gee Ondrej.E.Dyck j.mes R.Yates Aleksandar p.Ivanov j.shua B.Edel j.n A.Mol Department of Materials University of OxfordOxfordOX13PHUK School of Chemistry University of New South WalesSydneyNew South Wales 2052Australia Department of Chemistry Imperial College LondonLondonW120BZUK Center for Nanophase Materials Sciences Oak Ridge National LaboratoryOak RidgeTN 37830USA Instituto de Tecnologia Química e Biológica António Xavier Universidade Nova de LisboaAv.da RepúblicaOeiras 2780-157Portugal School of physics and Astronomy Queen Mary University of LondonLondonE14NSUK

Controlled breakdown has recently emerged as a highly accessible technique to fabricate solid-state ***,in its most common form,controlled breakdown creates a single nanopore at an arbitrary location in the ***,we introduce a new strategy whereby breakdown is performed by applying the electric field between an on-chip electrode and an electrolyte solution in contact with the opposite side of the *** demonstrate two advantages of this ***,we can independently fabricate multiple nanopores at given positions in the membrane by localising the applied field to the ***,we can create nanopores that are self-aligned with complementary nanoelectrodes by applying voltages to the on-chip electrodes to locally heat the membrane during controlled *** new controlled breakdown method provides a path towards the affordable,rapid,and automatable fabrication of arrays of nanopores self-aligned with complementary on-chip nanostructures.

关键词： solid-state nanopores dielectric breakdown nanofabrication single-molecule sensing nanopore arrays

丝氨酸蛋白酶活性和残留LEKTI的表达决定Netheron综合征的表型

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世界核心医学期刊文摘（皮肤病学分册） 2006年第10期2卷 18-19页

作者： Hachem j.-p. Wagberg F. Schmuth M. 党倩丽 Dienst Dermatologie and Toxicologie Academisch Ziekenhuis-Vrije Universiteit BrusselLaarbeeklaan 101Brussel 1090Belgium Dr.

Mutations in the SpINK5 gene encoding the serine protease(Sp)inhibitor,lymphoepithelial-Kazal-type 5 inhibitor(LEKTI),cause Netherton syndrome(ns),a life-threat-ening disease,owing to proteolysis of the stratum corneum(SC).We assessed here the basis for phenotypic variations in nine patients with “mild”,“moderate”,and “severe”*** magnitude of Sp activation correlated with both the barrier defect and clinical severity,and inversely with residual LEKTI *** co-localizes within the SC with kallikreins 5 and 7 and inhibits both *** permeability barrier abnormality in ns was further linked to SC thinning and proteolysis of two lipid hydrolases(β-glucocerebrosidase and acidic sphingomyelinase),with resultant disorganization of extracellular lamellar *** attenuation correlated with phenotype-dependent,Sp activation,and loss of corneodesmosomes,owing to desmoglein(DSG)1 and desmocollin(DSC)1 *** excess Sp activity extended into the nucleated layers in ns,degrading desmosomal mid-line structures with loss of DSG1/DSC1,the integrity of the nucleated epidermis appears to be maintained by comp.nsatory upregulation of DSG3/*** of sufficient permeability barrier function for survival correlated with a comp.nsatory acceleration of lamellar body secretion,providing a partial permeability barrier in *** studies provide a mechanistic basis for phenotypic variations in ns,and describe comp.nsatory mechanisms that permit survival of ns patients in the face of unrelenting Sp attack.

关键词： LEKTI Netheron 蛋白酶活性胞外膜激肽释放酶原板层小体渗透屏障防御屏障桥粒

Cerebral Vascular Accidents (CVA) Victims Conception and Birth Time-Links to Longevity, Lithuania, 1989-2013

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Health 2015年第1期7卷 161-166页

作者： E. Stoupel j. petrauskiene R. Kalediene S. Sauliune E. Abramson Division of Cardiology Rabin Medical Center Tel Aviv University Petah Tiqwa Israel Sackler Faculty of Medicine Tel Aviv University Petah Tiqwa Israel Department of Medical Management Lithuanian University of Medical Sciences Kaunas Lithuania Management Data Center Rabin Medical Center Petah Tiqwa Israel

In year 2001 a paper in the ANAS considered links between month of birth and longevity. In the following years we published four papers related to “big killers” (cardiac and oncology) that showed some differences in birth months distribution of this group and studied by LA, ns Gavrilov’s centenarians. The aim of this study was to study conception and birth months of another modern “big killer”—cerebral stroke (CVA) that is taking a leading role among cardiovascular causes of death in the last decades. Methods: 130,120 deaths of both gender CVA victims in Lithuania at 1989-2013 were studied. In addition to birth month, the months of conception (9 months before birth) were studied. Our data were compared with results of centenarians (birth of LA, ns Gavrilov’s study and transformed by authors also their conception month). Results: The maximum of births were j.nuary, March and May for CVA victims, while the analogical conception maximum were in April, j.ne, May and j.ly. The similar data for centenarians were that maximal births were in November, September, October (LA, ns Gavrilov) and conception in December, j.nuary, February. These results are similar to data related to cardiac and oncology deaths published in our previous publications. Conclusion: The conception and birth month of victims of CVA is different of similar data obtained by centenarians study. Different environmental conditions at different parts of the year and solar cycle can play a role affecting the embryo at early stages of development, predisposing to some pathologies in coming years of life.

关键词： Time Conception Birth Stroke CVA Longevity Big Killers

MRI在主动脉二叶瓣畸形、主动脉狭窄矫正术后患者随访中的作用

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世界核心医学期刊文摘（心脏病学分册） 2006年第1期2卷 59-60页

作者： Quenot j.-p. Boichot C. petit A. F. Brunotte 杜媛 Unitéd’IRM Hpital d’Enfants 2 Bd Marechal de Lattre-de-Tassigny 21 034 Dijon Cedex France

Background: The long-term outcome of repaired aortic coarctation may be complicated by dilatation of the ascending aorta notably in patients with bicuspid aortic valve. Magnetic resonance imaging was used to compare the size of the ascending aorta in patients with bicuspid or tricuspid aortic valve. Methods: In 50 patients with a repair of aortic coarctation, the size of the ascending aorta was measured in a bicuspid aortic valve group(n=11) and a tricuspid aortic valve group(n=39). The aortic diameter was measured at the level of the sinus of Valsalva and at the widest part of the ascending aorta using magnetic resonance imaging. Results: The mean age of patients at surgical repair was respectively 2.2±3.3 years for the bicuspid aortic valve group and 2.5±3.5 years for the tricuspid aortic valve group(p.ns) and the mean age at the time of the magnetic resonance imaging was 10.2±4.7 years and 9.3±5.9 years(p.ns) respectively. A significant difference in the aortic diameter was found between the bicuspid aortic valve group and the tricuspid aortic group both at the level of sinus of Valsalva(34.8±8.2 mm, 19.5±4.4 mm, respectively, ppectively, pns: The occurrence of ascending aortic dilatation is significantly associated with the presence of a bicuspid aortic valve. This requires long-term follow-up, which can be effectively performed by magnetic resonance imaging.

关键词：主动脉二叶瓣畸形主动脉狭窄术后患者矫正手术 MRI 升主动脉扩张主动脉直径随访并发症测量

A tale of motor neurons and CD4＋ T cells： moving forward by looking back

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Neural Regeneration Research 2017年第4期12卷 562-565页

作者： Abhirami Kannan Iyer Kathryn j.j.nes Department of Anatomy and Cell Biology Indiana University School of Medicine

Amyotrophic lateral sclerosis （ALS） is a fatal progressive disorder characterized by the selective degeneration of motor neurons （MN）. The impact of peripheral immune status on disease progression and MN survival is becoming increasingly recognized in the ALS research field. In this review, we briefly discuss findings from mouse models of peripheral nerve inj.ry and immunodeficiency to understand how the immune system regulates MN survival. We extend these observations to similar studies in the widely used superoxide dismutase 1 （SOD1） mouse model of ALS. Last, we present future hypotheses to identify potential causative factors that lead to immune dysregulation in ALS. The lessons from preceding work in this area offer new exciting directions to bridge the gap in our current understanding of immune mediated neuroprotection in ALS.

关键词： amyotrophic lateral sclerosis (ALS) superoxide dismutase 1 (SOD1) immune system SOD1 mice motor neuron CD4+ T cells neuroprotection