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Does Ethanol Play a Pro-Oxidant Role during Oxidative stress in the Liver?

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journal of Biosciences and Medicines 2015年第8期3卷 1-9页

作者： Patience O. Obih joseph s. soblosky barry j. Potter College of Pharmacy Xavier University of Louisiana New Orleans USA The Alcohol Research Center LSU Health New Orleans USA The Department of Physiology at LsU Health New Orleans USA

Oxidative stress has been implicated in the pathophysiology of liver injury during xenobiotic and alcohol metabolism, ischemia/reperfusion injury. In this study we examined if ethanol acted as a pro-oxidant making cells become more sensitive to tert-butylhydroperoxide (tBH) killing. Cell viability was determined in a rat hepatoma cell line (FTO2B) and rat primary hepatocytes in culture in the presence or absence of ethanol pretreatment. To elucidate the contribution of labile iron, deferoxamine (DF, an iron chelator) or lipid free radicals, N,N-diphenyl-p-phenylenediamine (DPPD, a lipid scavenger) were added to the ethanol tBH co-treatment. The levels of glutathione (GsH) and glutathione disulfide (GssG) in the hepatocytes were also measured. Ethanol treatment (both pretreatment and co-treatment during the 3-hr tBH exposure) increased cell killing dramatically in both FTO2B cells and primary rat hepatocytes. Both DF and DPPD decreased ethanol-enhanced tBH cell killing in hepatocytes. These results demonstrated that co-treatment of FTO2B cells and primary rat hepatocytes with ethanol and tBH increased cell killing. The GsH level was dramatically reduced while GssG level rose. Both DFP and DPPD reversed or protected the cells from this insult, indicating that ethanol was a pro-oxidant.

关键词： Ethanol Liver Hepatocytes FTO2B Cells t-Butyl Hydroperoxide

Clinical laboratory and imaging evidence for effectiveness of agarose-agarose macrobeads containing stem-like cells derived from a mouse renal adenocarcinoma cell population (RMBs) in treatment-resistant, advanced metastatic colorectal cancer:Evaluation of

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Chinese journal of Cancer Research 2018年第1期30卷 72-83页

作者： barry H.smith Lawrence s.Gazda Thomas j.Fahey Angelica Nazarian Melissa A.Laramore Prithy Martis Zoe P.Andrada joanne Thomas Tapan Parikh sudipta sureshbabu Nathaniel Berman Allyson j.Ocean Richard D.Hall David j.Wolf The Rogosin Institute New York NY 10021 USA The Rogosin Institute-Xenia Division Xenia OH 45385 USA New York Presbyterian-Weill Cornell Medical Center New York NY 10021 USA Bob Evans Farms Inc. New Albany OH 43054 USA

Objective： The complexity, heterogeneity and capacity of malignant neoplastic cells and tumors for rapid change and evolution suggest that living-cell-based biological-systems approaches to cancer treatment are merited. Testing this hypothesis, the tumor marker, metabolic activity, and overall survival（Os） responses, to the use of one such system, implantable macrobeads [RENCA macrobeads（RMBs）], in phase I and IIa clinical trials in advanced,treatment-resistant metastatic colorectal cancer（m CRC） are described ***： Forty-eight m CRC patients（30 females; 18 males）, who had failed all available, approved treatments,underwent RMB implantation（8 RMB/kg body weight） up to 4 times in phase I and phase IIa open-label ***, labs [tumor and inflammation markers, lactate dehydrogenase（LDH）] and positron emission tomography-computed tomography（PET-CT） imaging to measure number/volume and metabolic activity of the tumors were performed pre-and 3-month-post-implantation to evaluate safety and initial efficacy（as defined by biological responses）. PET-CT maximum standard uptake value（sUVmax）（baseline and d 90; sUVmax ≥2.5）, LDH,and carcinoembryonic antigen（CEA） and/or cancer antigen 19-9（CA 19-9） response（baseline, d 30 and/or d 60）were assessed and compared to ***： Responses after implantation were characterized by an at least 20% decrease in CEA and/or CA 19-9 in75% of patients. Fluorodeoxyglucose（FDG）-positive lesions（phase I, 39; 2 a, 82） were detected in 37/48 evaluable patients, with 35% stable volume and stable or decreased sUV（10） plus four with necrosis; 10, increased tumor volume, sUV. LDH levels remained stable and low in Responders（R）（d 0–60, 290.4–333.9）, but increased steadily in Non-responders（NR）（d 0–60, 382.8–1,278.5）（d 60, P=0.050）. Responders to RMBs, indicated by the changes in the above markers, correlated with Os（R mean Os=10.76 months; NR mean Os=4.9 months; P=0.0006）.Conclusions： The correlations of the tumor marker, tumor volume

关键词： Clinical trial systems-biology RENCA macrobeads metastatic colorectal cancer colon cancer

Postpartum meloxicam administration alters plasma haptoglobin, polyunsaturated fatty acid, and oxylipid concentrations in postpartum ewes

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journal of Animal science and Biotechnology 2020年第4期11卷 1047-1060页

作者： Katie EOlagaray barry j.Bradford Lorraine M.sordillo jeffery C.Gandy Laman K.Mamedova Turner H.swartz Trey D.jackson Emma K.Persoon Caitlin s.shugart Curtis R.Youngs Department of Animal sciences and Industry Kansas State UniversityManhattan 66506USA College of Veterinary Medicine Michigan State University2265K Anthony HallEast LansingMI 48824-1225USA Department of Animal science Iowa State UniversityAmesIAUSA.

Background: Postpartum inflammation is a natural and necessary response;however, a dysfunctional inflammatory response can be detrimental to animal productivity. The objective of this study was to determine the effects of a non-steroidal anti-inflammatory drug(meloxicam) on ewe postpartum inflammatory response, ewe plasma polyunsaturated fatty acid and oxylipid concentrations, and lamb ***: After lambing, 36 Hampshire and Hampshire × suffolk ewes were sequentially assigned within type of birth to control(n = 17) or meloxicam orally administered on d 1 and 4 of lactation(MEL;90 mg, n = 19). Milk and blood samples were collected on d 1(prior to treatment) and d 4. Milk glucose-6-phosphate was not affected by MEL. Plasma haptoglobin(Hp) concentrations were less for MEL ewes;control ewes with greater d 1 Hp concentrations had elevated Hp on d 4, but this was not the case for MEL-treated ewes. Treatment with MEL increased plasma arachidonic acid concentration by more than 4-fold in ewes rearing singles but decreased concentrations of 9,10-dihydroxyoctadecenoic acid, prostaglandin F2α, 8-iso-prostaglandin E2, and 8,9-dihydroxyeicosatetraenoic acid. Nine oxylipids in plasma had interactions of treatment with d 1 Hp concentration,all of which revealed positive associations between d 1 Hp and d 4 oxylipid concentrations for CON, but neutral or negative relationships for MEL. MEL decreased 13-hydroxyoctadecadienoic acid:13-oxooctadecadienoic acid ratio and tended to increase 9-hydroxyoctadecadienoic acid:9-oxooctadecadienoic acid ratio(both dependent on d 1 values), indicating progressive metabolism of linoleic acid-derived oxylipids occurred by enzymatic oxidation after MEL treatment. Meloxicam reduced oxylipids generated across oxygenation pathways, potentially due to an improved redox ***: Postpartum MEL treatment of ewes decreased plasma concentrations of Hp and several oxylipids,with the greatest impact in ewes with biomarkers reflecting a greate

关键词： Eicosanoid Inflammation Lactation Nonsteroidal anti-inflammatory drug sheep

Analysis of core protein clusters identifies candidate variable sites conferring metronidazole resistance in Helicobacter pylori

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Gastroenterology Report 2019年第1期7卷 42-49,I0002页

作者： Eng-Guan Chua Aleksandra W.Debowski KMary Webberley Fanny Peters Binit Lamichhane Mun-Fai Loke jamuna Vadivelu Chin-Yen Tay barry j.Marshall Michael j.Wise The Marshall Centre for Infectious Diseases Research and Training University of Western AustraliaPerthWestern AustraliaAustralia school of Biomedical sciences Faculty of Health and Medical SciencesUniversity of Western AustraliaPerthWestern AustraliaAustralia Department of Medical Microbiology University of MalayaKuala LumpurWilayah PersekutuanMalaysia shenzhen Dapeng New District Kuichong People Hospital ShenzhenGuangdongChina UM Marshall Centre University of MalayaKuala LumpurWilayah PersekutuanMalaysia school of Computer science and software Engineering University of Western AustraliaPerthWestern AustraliaAustralia

Background:Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori ***,the global emergence of metronidazole resistance in Hp poses a major challenge to health *** of RdxA is known to be a major mechanism of conferring metronidazole resistance in ***,metronidazole resistance can also arise in *** strains expressing functional RdxA protein,suggesting that there are other mechanisms that may confer resistance to this ***:We performed whole-genome sequencing on 121 *** clinical strains,among which 73 were ***-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was *** sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in ***:Resistance due to RdxA truncation was identified in 34%of metronidazole-resistant *** of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole *** sites included R16H/C in RdxA,D85N in the inner-membrane protein RclC(HP0565),V265I in a biotin carboxylase protein(HP0370)and A51V/T in a putative threonylcarbamoyl–AMP synthase(HP0918).Conclusions:Our approach identified new potential mechanisms for metronidazole resistance in *** that merit further investigation.

关键词： Helicobacter pylori metronidazole antibiotic resistance whole-genome sequencing core protein clusters sequence alignment

Burnout in the emergency department: Randomized controlled trial of an attention-based training program

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journal of Integrative Medicine 2019年第3期17卷 173-180页

作者： Pádraic j.Dunne julie Lynch Lucia Prihodova Caoimhe O'Leary Atiyeh Ghoreyshi sharee A.Basdeo Donal j.Cox Rachel Breen Ali sheikhi áine Carroll Cathal Walsh Geraldine McMahon barry White Trinity Translational Medicine Institute Trinity College Research Department Royal College of Physicians of Ireland Department of Innovation Fitbit Inc. Health Research Institute Main BuildingUniversity of Limerick Health service Executive Dr Steevens' Hospital Department of Emergency Medicine St.James' s Hospital National Centre for Hereditary Coagulation Disorders St.James' s Hospital

Background: Burnout(encompassing emotional exhaustion, depersonalization and personal accomplishment) in healthcare professionals is a major issue worldwide. Emergency medicine physicians are particularly affected, potentially impacting on quality of care and attrition from the ***: The aim of this study was to apply an attention-based training(ABT) program to reduce burnout among emergency multidisciplinary team(MDT) members from a large urban ***, setting, participants and interventions: Emergency MDT members were randomized to either a notreatment control or an intervention group. Intervention group participants engaged in a four session(4 h/session) ABT program over 7 weeks with a practice target of 20 min twice-daily. Practice adherence was measured using a smart phone application together with a wearable Charge 2 *** outcome measures: The primary outcome was a change in burnout, comprising emotional exhaustion, depersonalization and personal achievement. The secondary outcomes were changes in other psychological and biometric ***: The ABT program resulted in a significant reduction(P s T3 [follow-up at two months after intervention]) in burnout, specifically, emotional exhaustion, with an effect size(probability of superiority) of 59%. similar reductions were observed for stress(P s demonstrated significant improvements in heart rate variability, resting heart rate, sleep as well as an increase in pro-inflammatory cytokine ***: This study describes a positive impact of ABT on emergency department staff burnout compared to a no-treatment control group.

关键词： Burnout Emotional exhaustion Meditation Healthcare professional sleep stress Cytokines Cortisol Randomized controlled trial

Multi-Institutional Us Experience of the Occlutech AFR Device in Congenital and Acquired Heart Disease

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Congenital Heart Disease 2022年第1期17卷 107-116页

作者： barry O’Callaghan jenny Zablah joseph Vettukattil Daniel Levi Morris salem Allison Cabalka jason Anderson Makram Ebeid Ryan Alexy Gareth j.Morgan The Heart Institute Children’s Hospital ColoradoAuroraUSA Pediatric Cardiology Helen DeVos Children’s HospitalGrand RapidsUSA Pediatric Cardiology UCLA HealthMattel Children’s HospitalLos AngelesUSA Pediatric Cardiology UCLA Medical CentreLos AngelesUSA Pediatric Cardiology Mayo ClinicRochesterUSA Pediatric Cardiology University of Mississippi Medical CenterJacksonUSA Pediatric Cardiology Riley Hospital for Children at Indiana University HealthIndianapolisUSA

Objectives:To detail the Us multi-institutional experience with the Occlutech©(Occlutech International AB,Helsingborg,sweden)atrial flow regulator(AFR)in children and adults with acquired or congenital heart ***:The creation of a long-term atrial communication is desirable in several cardiovascular disease phenotypes,most notably pulmonary arterial hypertension,disorders of increased left ventricular filling and increased cavopulmonary pressures in patients with a Fontan type ***:Patients were identified for inclusion from the AFR device manufacturer *** was collected using a RedCap database following IRB approval.8 weeks of follow up data was sought for each patient based on available *** was analyzed and summarized using ***:We report the experience of 6 Us centers in the implantation of AFR devices in 15 patients,across a wide age range,with different disease phenotypes and a variety of *** was technically successful in all patients and improvement was noted in both clinical and hemodynamic *** were no immediate or intermediate term complications reported.3 patients died remote from *** deaths were not felt to be related to the AFR device or related procedural ***:Compassionate use of the AFR device in children and adults with congenital&acquired heart disease is technically feasible and produces beneficial short term hemodynamic and symptomatic *** uptake of this technique and treatment at specialist centers has the potential to provide significant benefits to a variety of complex patients with currently limited treatment options and indeterminate prognosis.

关键词： Congenital heart disease pulmonary hypertension left atrial hypertension single ventricle palliation diastolic heart failure

Multitarget stool DNA for colorectal cancer screening:A review and commentary on the United states Preventive services Draft Guidelines

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World journal of Gastrointestinal Oncology 2016年第5期8卷 450-458页

作者： barry M Berger Bernard Levin Robert j Hilsden Medical Affairs Exact Sciences Corporation scientific Advisory Board Exact Sciences Departments of Medicine and Community Health sciences University of Calgary

Multitarget stool DNA(mt-sDNA) testing was approved for average risk colorectal cancer(CRC) screening by the United states Food and Drug Administration and thereafter reimbursed for use by the Medicare program(2014).The United states Preventive services Task Force(UsPsTF) October 2015 draft recommendation for CRC screening included mt-s DNA as an "alternative" screening test that "may be useful in select clinical circumstances",despite its very high sensitivity for early stage *** evidence supporting mt-s DNA for routine screening use is *** clinical efficacy of mt-s DNA as measured by sensitivity,specificity,life-years gained(LYG),and CRC deaths averted is similar to or exceeds that of the other more specifically recommended screening options included in the draft document,especially those requiring annual testing *** a population with primarily irregular screening participation,tests with the highest point sensitivity and reasonable specificity are more likely to favorably impact CRC related morbidity and mortality than those depending on annual *** paper reviews the evidence supporting mt-s DNA for routine screening and demonstrates,using UsPsTF's modeling data,that mt-s DNA at three-year intervals provides significant clinical net benefits and fewer complications per LYG than annual fecal immunochemical testing,high sensitivity guaiac based fecal occult blood testing and 10-year colonoscopy screening.

关键词： Colorectal cancer screening Multitarget stool DNA stool DNA The United states Preventive services Task Force Cancer Intervention surveillance Modeling Network Fecal immunological technique Modeling Interval

Targeted quantitative profiling of metabolites and gene transcripts associated with 4-aminobutyrate (GABA) in apple fruit stored under multiple abiotic stresses

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Horticulture Research 2018年第1期5卷 66-79页

作者： Carolyne j.Brikis Adel Zarei Greta Z.Chiu Kristen L.Deyman jingyun Liu Christopher P.Trobacher Gordon j.Hoover sanjeena subedi jennifer R.DeEll gale G.Bozzo barry j.shelp Department of Plant Agriculture University of GuelphGuelphOntarioN1G 2W1Canada Department of Mathematical sciences Binghamton UniversityBinghamtonNY13902USA Ontario Ministry of Agriculture Food and Rural AffairsBox 5871283 Blueline Rd.at Highway 3SimcoeOntarioN3Y 4N5Canada

4-Aminobutyrate accumulates in plants under abiotic ***,targeted quantitative profiling of metabolites and transcripts was conducted to monitor glutamate-and polyamine-derived 4-aminobutyrate production and its subsequent catabolism to succinate or 4-hydroxybutyrate in apple(Malus x domestica Borkh.)fruit stored at 0°C with 2.5 kPa O2 and 0.03 or 5 kPa CO2 for 16 ***-temperature-induced protein hydrolysis appeared to be responsible for the enhanced availability of amino acids during early storage,and the resulting higher glutamate level stimulated 4-aminobutyrate levels more than *** CO2 increased the levels of polyamines,as well as succinate and 4-hydroxybutyrate,during early storage,and 4-aminobutyrate and 4-hydroxybutyrate over the longer *** of all of the genes likely involved in 4-aminobutyrate metabolism from glutamate/polyamines to succinate/4-hydroxybutyrate was induced in a co-ordinated ***2-regulated expression of apple GLUTAMATE DECARBOXYLAsE 2,AMINE OXIDAsE 1,ALDEHYDE DEHYDROGENAsE 10A8 and POLYAMINE OXIDAsE 2 was evident with longer term *** suggested that respiratory activities were restricted by the elevated CO2/O2 environment,and that decreasing NAD+availability and increasing NADPH and NADPH/NADP+,respectively,played key roles in the regulation of succinate and 4-hydroxybutyate ***,these findings suggest that both transcriptional and biochemical mechanisms are associated with 4-aminobutyrate and 4-hydroxybutyrate metabolism in apple fruit stored under multiple abiotic stresses.

关键词： hydrolysis subsequent restricted

Roost selection of the endangered spotted Greenshank(Tringa guttifer) in critical habitat in the Inner Gulf of Thailand

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Avian Research 2019年第2期10卷 199-208页

作者： Chenxing Yu Dusit Ngoprasert Philip D.Round Andrew j.Pierce Tommaso savini George A.gale Conservation Ecology Program School of Bioresources and TechnologyKing Mongkut’s University of Technology ThonburiBangkok 10150Thailand. Department of Biology Mahidol UniversityRama 6 RoadBangkok 10400Thailand

Background: Roost-site quality can significantly affect the individual fitness of shorebirds, but roost sites remain poorly described for many threatened species on the East Asian–Australasian Flyway. We studied roost-site selection of the globally endangered spotted Greenshank (Tringa guttifer) in the Inner Gulf of Thailand, an area which supports approximately 24% of their global wintering population, during two non-breeding seasons (October 2014–May 2015 and December 2015–February 2016). Methods: We measured nine variables associated with roost site characteristics including water depth, indicators of disturbance/predation risk, and associations with other shorebird species. We predicted that roost ponds with shallow water in proximity to foraging sites would receive higher usage than those further away. Results: A total of 94 sites were measured of which 46 were used for roosts with 23 used repeatedly. All used sites were human-modified ponds, of which 44 were used for salt farming and two used for aquaculture. Roosts were on average 1.10 ± 0.78 (sE) km from foraging sites and 5.8 ± 2.4 cm deep. The most supported model indicated that roost sites were negatively associated with distance to foraging sites and positively associated with the presence of Grey Plover (Pluvialis squatarola) and water depth. Conclusions: Traditional saltpans and other artificial wetlands near (s serve as the primary high-tide roost habitat in the Inner Gulf of Thailand for this spotted Greenshank population and perhaps seven other globally threatened or near-threatened species. Critically, all observed roost sites are on private land with no formal protection and thus will require creative public–private partnerships to manage sustainably.

关键词： Habitat selection saltpans shorebirds