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Low-dose morphine elicits ventilatory excitant and depressant responses in conscious rats: Role of peripheral <i>µ</i>-opioid receptors

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Open j.urnal of Molecular and Integrative Physiology 2013年第3期3卷 111-124页

作者： Fraser Henderson j.. Walter j. May Ryan B. Gruber Alex P. Young Lisa A. Palmer Benj.min Gaston stephen j. lewis Pediatric Respiratory Medicine University of Virginia School of Medicine Charlottesville USA Division of Biology Galleon Pharmaceuticals Horsham USA Department of Pediatrics Case Western Reserve University Cleveland USA

The systemic administration of morphine affects ventilation via a mixture of central and peripheral actions. The aims of this study were to characterize the ventilatory responses elicited by a low dose of morphine in conscious rats;to determine whether tolerance develops to these responses;and to determine the potential roles of peripheral μ-opioid receptors (μ-ORs) in these responses. Ventilatory parameters were monitored via unrestrained whole-body plethysmography. Conscious male Sprague-Dawley rats received an intravenous inj.ction of vehicle or the peripherally-restricted μ-OR antagonist, naloxone methiodide (NLXmi), and then three successive inj.ctions of morphine (1 mg/kg) given 30 min apart. The first inj.ction of morphine in vehicle-treated rats elicited an array of ventilatory excitant (i.e., increases in frequency of breathing, minute volume, respiratory drive, peak inspiratory and expiratory flows, accompanied by decreases in inspiratory time and end inspiratory pause) and inhibitory (i.e., a decrease in tidal volume and an increase in expiratory time) responses. Subsequent inj.ctions of morphine elicited progressively and substantially smaller responses. The pattern of ventilatory responses elicited by the first inj.ction of morphine was substantially affected by pretreatment with NLXmi whereas NLXmi minimally affected the development of tolerance to these responses. Low-dose morphine elicits an array of ventilatory excitant and depressant effects in conscious rats that are subj.ct to the development of tolerance. Many of these initial actions of morphine appear to involve activation of peripheral μ-ORs whereas the development of tolerance to these responses does not.

关键词： Morphine Minute Ventilation Tolerance Peripheral and Central Opioid Receptors Conscious Rats

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Morphine has latent deleterious effects on the ventilatory responses to a hypoxic challenge

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Open j.urnal of Molecular and Integrative Physiology 2013年第3期3卷 166-180页

作者： Walter j. May Ryan B. Gruber j.seph F. Discala Velj.o Puskovic Fraser Henderson j.. Lisa A. Palmer stephen j. lewis Pediatric Respiratory Medicine University of Virginia School of Medicine Charlottesville USA Division of Biology Galleon Pharmaceuticals Horsham USA

The aim of this study was to determine whether morphine depresses the ventilatory responses elicited by a hypoxic challenge (10% O2, 90% N2) in conscious rats at a time when the effects of morphine on arterial blood gas (ABG) chemistry, Alveolar-arterial (A-a) gradient and minute ventilation (Vm) had completely subsided. In vehicle-treated rats, each episode of hypoxia stimulated ventilatory function and the responses generally subsided during each normoxic period. Morphine (5 mg/kg, i.v.) induced an array of depressant effects on ABG chemistry, A-a gradient and Vm (via decreases in tidal volume). Despite resolution of these morphine-induced effects, the first episode of hypoxia elicited substantially smaller increases in Vm than in vehicle-treated rats, due mainly to smaller increases in frequency of breathing. The pattern of ventilatory responses during subsequent episodes of hypoxia and normoxia changed substantially in morphine-treated rats. It is evident that morphine haslatent deleterious effects on ventilatory responses elicited by hypoxic challenge.

关键词： Morphine Hypoxia Minute Ventilation Arterial Blood Gas Chemistry Conscious Rats

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Comparative utility of vestibular function tests in patients with peripheral and central vestibular dysfunction

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j.urnal of Otology 2024年第1期19卷 5-9页

作者： Cameron B.Fattahi Christopher Zaro j.nice j.Chung Richard F.lewis Divya A.Chari Department of Otolaryngology-Head and Neck Surgery UMASS Memorial Medical CenterUniversity of Massachusetts Chan Medical SchoolWorcesterMAUSA j.nks Vestibular Physiology Laboratory Massachusetts Eye and EarBostonMAUSA Department of Otolaryngology-Head and Neck Surgery Massachusetts Eye and EarHarvard Medical SchoolBostonMAUSA Department of Neurology Harvard Medical SchoolBostonMAUSA

Background: Bithermal caloric irrigation, video head impulse test(vHIT), and rotational testing are commonly used to assess peripheral vestibular function, but the relative clinical utility of each test in differentiating patients with peripheral vestibulopathy is ***: To determine whether(1) the combination of two or more vestibular tests enhances diagnostic utility over a single test;(2) abnormal test results on vestibular tests correlate with one ***: Retrospective analysis of data collected from multidisciplinary vestibular clinics at two academic medical centers from 2016 to ***: 150 patients(54.10 ± 15.09 years, 88 females) were included. No individual test was significantly better at predicting the presence of peripheral vestibular damage(p > 0.05). vHIT test results improved significantly when combined with either the caloric test(p = 0.007) or rotary chair test(p = 0.039). Caloric and rotational testing had high sensitivity(74.65% and 76.06%, respectively) and specificity(83.54% and 78.48%, respectively). vHIT demonstrated excellent specificity(89.87%) but poor sensitivity(47.89%). Caloric, vHIT, and rotary chair tests results did not correlate with one another(p > 0.05).Conclusions: Vestibular function tests have comparable diagnostic utility, yet each offers unique advantages. Caloric and rotational testing may be best suited for screening peripheral damage and vHIT may function ideally as a confirmatory test.

关键词： vestibular patients specificity

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Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

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Cellular & Molecular Immunology 2024年第1期21卷 33-46页

作者： Anj. Meyer Stephanie R.Zack Wes Nij.m Adel Burgos Vishwa Patel Brian Zanotti Michael V.Volin M.Asif Amin Myles j.lewis Costantino Pitzalis Shiva Arami j.seph A.Karam Nadera j.Sweiss Shiva Shahrara j.sse Brown VA Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Division of Rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA Centre for Experimental Medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom Centre for Experimental Medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

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Management of distal cholangiocarcinoma with arterial involvement: Systematic review and case series on the role of neoadj.vant therapy

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World j.urnal of Gastrointestinal Surgery 2024年第8期16卷 2689-2701页

作者： lewis A Hall Duncan Loader Santiago Gouveia Marta Burak j.mes Halle-Smith Peter Labib Moath Alarabiyat Ravi Marudanayagam Bobby V Dasari Keith j.Roberts Syed S Raza Michail Papamichail David C Bartlett Robert P Sutcliffe Nikolaos A Chatzizacharias Department of Hepatopancreatobiliary Surgery and Liver Transplantation University Hospitals Birmingham NHS Foundation TrustBirmingham B152GWUnited Kingdom Institute of Immunology and Immunotherapy University of BirminghamBirmingham B152TTUnited Kingdom College of Medical and Dental Sciences University of BirminghamBirmingham B152TTUnited Kingdom Institute of Clinical Sciences University of BirminghamBirmingham B152TTUnited Kingdom

BACKGROUND The use of neoadj.vant therapy(NAT)in distal cholangiocarcinoma(dCCA)with regional arterial or extensive venous involvement,is not widely accepted and evidence is *** To synthesise evidence on NAT for dCCA and present the experience of a highvolume tertiary-centre managing dCCA with arterial *** A systematic review was performed according to PRISMA guidance to identify all studies reporting outcomes of patients with dCCA who received *** patients from 2017 to 2022 who were referred for NAT for dCCA at our centre were retrospectively collected from a prospectively maintained *** characteristics,NAT type,progression to surgery and oncological outcomes were *** Twelve studies were *** definition of“unresectable”locally advanced dCCA was *** studies reported outcomes for 9 patients who received NAT for dCCA with extensive vascular involvement.R0 resection rate ranged between 0 and 100%but without survival benefit in most *** studies considered either NAT in resectable dCCA or inclusive with extrahepatic *** presented case series includes 9 patients(median age 67,IQR 56-74 years,male:female 5:4)referred for NAT for borderline resectable or locally advanced *** patients progressed to surgery and 2 were *** patient died at 14 months with evidence of recurrence at 6 months and the other died at 51 months following recurrence 6 months *** Evidence for benefit of NAT is *** on criteria for uniform definition of resectability for dCCA is *** propose using the established National-Comprehensive-Cancer-Network®criteria for pancreatic ductal adenocarcinoma.

关键词： Cholangiocarcinoma Neoadj.vant therapy Arterial involvement Locally advanced Systematic review

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Effects of single and dual species herbivory on the behavioral responses of three thrips species to cotton seedlings

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Insect Science 2017年第4期24卷 684-698页

作者： Rehan Silva Gimme H. Walter lewis j. Wilson Michael j. Furlong School of Biological Sciences The University of Queensland St. Lucia Queensland 4072 Australia Cotton Research Unit CSIRO Agriculture Flagship Locked Bag 59 Narrabri NSW 2390 Australia

This study investigated the olfactory responses of 3 thrips species [Frankliniella schultzei Trybom, E occidentalis Pergrande and Thrips tabaci Lindeman （Thysanoptera： Thripidae）] to cotton seedlings [Gossypium hirsutum L. （Malvales： Malvaceae）] simulta- neously damaged by different combinations of herbivores. Cotton seedlings were damaged by foliar feeding Tetranychus urticae Koch （Trombidiforms： Tetranychidae）, Helicoverpa armigera Hibner （Lepidoptera： Noctuidae）, Aphis＇ gossypii Glover （Hemiptera： Aphidi- dae） or root feeding Tenebrio molitor L. （Coleoptera： Tenebrionidae）. Thrips responses to plants simultaneously damaged by 2 species of herbivore were additive and equivalent to the sum of the responses of thrips to plants damaged by single herbivore species feeding alone. For example, E occidentalis was attracted to T. urticae damaged plants but more attracted to undamaged plants than to plants damaged by H. armigera. Plants simultane- ously damaged by low densities of T. urticae and H. armigera repelled E occidentalis but as T. urticae density increased relative to H. armigera density, E occidentalis attraction to coinfested plants increased proportionally. Thrips tabaci did not discriminate between un- damaged plants and plants damaged by H. armigera but were attracted to plants damaged by T. urticae alone or simultaneously damaged by T. urticae and H. armigera. Olfactometer assays showed that simultaneous feeding by 2 herbivores on a plant can affect predator- prey interactions. Attraction of F. occidentalis to plants damaged by its T. urticae prey was reduced when the plant was simultaneously damaged by H. armigera, T. molitor, or A. gossypii and F. schultzei was more attracted to plants simultaneously damaged by T. urticae and H. armigera than to plants damaged by T. urticae alone. We conclude that plant responses to feeding by I species of herbivore are affected by responses to feeding by other herbivores. These plant-mediated interactions between herbivo

关键词： attraction dual-herbivory Frankliniella occidentalis Frankliniella schultzei induced responses predictability simultaneous damage Thrips tabaci

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Effect of the postfeeding interval on olfactory responses of thrips to herbivore-induced cotton plants

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Insect Science 2016年第6期23卷 881-892页

作者： Rehan Silva Gimme H. Walter lewis j. Wilson Michael j. Furlong School of Biological Sciences University of Queensland St. Lucia Queensland 4072 Cotton Research Unit CSIRO Agriculture Flagship Narrabri NSW 2390 Austrafia

We investigated the responses of 3 thrips species, Frankliniella schultzei Tryborn, E occidentalis Pergrande, and Thrips tabaci Lindeman （Thysanoptera： Thripidae） to herbivore-damaged and undamaged cotton seedlings （Gossypium hirsutum L. [Malvales： Malvaceae]） at a range of time intervals following damage by adult Tetranychus urticae （Koch）, adult T. ludeni （Zacher）（Acari： Tetranychidae） or Helicoverpa armigera （Hubner）（Lepidoptera： Noctuidae） larvae in olfactometer assays. The intensity/frequency of the response of thrips to herbivore-induced plants decreased with time and ultimately disappeared in all cases; however, the rate at which the response declined was related to the herbivore species that inflicted the damage. All 3 species of thrips were attracted to plants damaged by T. urticae for longer than they were to plants damaged by T. ludeni. The duration for which damaged plants remained attractive was also affected by the degree of damage inflicted on cotton seedlings. For example, E schultzei was attracted to plants damaged by a higher density of two-spotted spider mites （100/plant） for much longer than to plants damaged by a lower density of these mites （50/plant）. The results reinforce previous studies that demonstrate that arrangement of variables influences the responses of thrips to their herbivore-induced cotton host plants. Results also show that these responses are variable in time following herbivore damage to cotton plants, which further demonstrates how difficult it is to generalize about the functional significance of these interactions.

关键词： attraction cotton duration induced responses olfactometer Thysanoptera

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Volumetric measurement of rock movement using photogrammetry

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International j.urnal of Mining Science and Technology 2016年第1期26卷 123-130页

作者： Benton Donovan j. Iverson stephen R. Martin lewis A. j.hnson j.ffrey C. Raffaldi Michael j. National Institute for Occupational Safety and Health. Spokane 99207 USA

NIOSH ground control safety research program at Spokane,Washington,is exploring applications of photogrammetry to rock mass and support monitoring. This paper describes two ways photogrammetric techniques are being used. First,photogrammetric data of laboratory testing is being used to correlate energy input and support deformation. This information can be used to infer remaining support toughness after ground deformation events. This technique is also demonstrated in a field ***,field photogrammetric data is compared to crackmeter data from a deep underground *** were found to average 8 mm,but have produced results within 0.2 mm of true displacement,as measured by crackmeters. Application of these techniques consists of monitoring overall fault activity by monitoring multiple points around the crackmeter. A case study is provided in which a crackmeter is clearly shown to have provided insufficient information regarding overall fault ground *** is proving to be a useful ground monitoring tool due to its unobtrusiveness and ease of use.

关键词： PhotogrammetryGround controlMonitoringDeep vein miningVolume calculationCrackmeter

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A Putative Nuclear CLE-Like （CLEL） Peptide Precursor Regulates Root Growth in Arabidopsis

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Molecular Plant 2012年第4期5卷 955-957页

作者： Ling Meng Bob B. Buchanan lewis j. Feldman Sheng Luan Department of Plant and Microbial Biology University of California Berkeley CA USA

Dear Editor, It is well established that local intercellular signaling net- works control cell identity and activity. Secreted peptides have been found to play a central role in this capacity in plants （Matsubayashi and Sakagami, 2006; Meng et al., 2010; Meng, 2012）. CLEL, which is the term for CLE （CLV3/ESR-related）-Iike peptides （also previously named as RGFs for root growth fac- tors by Matsuzaki et al. （2010））, regulate root growth pattern and lateral root development in Arabidopsis （Matsuzaki et al., 2010; Meng et al., 2012）. CLEL peptide precursors contain an N-terminal signal peptide （hydrophobic patch）, a diverse vari- able region,

关键词： ROLES CONVERTASES

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Early developmental exposure to inorganic mercury does not alter affiliative behavior of adult prairie voles(Microtus ochrogaster)

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Integrative Zoology 2018年第6期13卷 761-768页

作者： Yue CHEN Robert lewis j.Thomas CURTIS Department of Pharmacology and Physiology Oklahoma State University Center for Health SciencesTulsaOklahomaUK

Mercury chloride exposure through drinking water in adult male prairie voles(Microtus ochrogaster)has been shown to alter their social ***,we examined the potential disruption of adult social behavior in prairie voles that were exposed to 60 ppm mercury during early *** used a cross-fostering approach to test the effects of mercury exposure:(1)from conception until birth;(ii)from birth until weaning;and(iii)from conception until weaning,on adult affiliative *** and mercury-treated voles were given the option of remaining in an empty cage or affiliating with a same-sex conspecific in a 3-h choice *** found that early developmental mercury exposure had little if any effect on the reproductive success of breeder pairs or on affiliative behavior by either sex when subj.cts were tested as *** results suggest that,at least in the context of the behavior tested,the effects of early developmental exposure to mercury do not permanently alter adult prairie vole affiliative behavior,or do so in a way that is too subtle to be detected using the current testing paradigm.

关键词： behavioral testing metals toxicity social behavior prairie vole

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