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Acute systemic accumulation of acrolein in mice by inhalation at a concentration similar to that in cigarette smoke

Neuroscience Bulletin 2014年第6期30卷 1017-1024页

作者： melissa tully Lingxing Zheng Glen Acosta Ran Tian Riyi Shi Weldon School of Biomedical Engineering Purdue UniversityWest LafayetteINUSA Indiana University School of Medicine IndianapolisINUSA Department of Basic Medical Sciences College of Veterinary MedicinePurdue UniversityWest LafayetteINUSA

Cigarette smoke is an important environmental factor associated with a wide array of public health concerns. Acrolein, a component of tobacco smoke and a known toxin to various cell types, may be a key pathological factor mediating the adverse effects linked with tobacco smoke. Although acrolein is known to accumulate in the respiratory system after acute nasal exposure, it is not clear if it accumulates systemically, and less is known in the nervous system. The aim of this study was to assess the degree of acrolein accumulation in the circulation and in the spinal cord following acute acrolein inhalation in mice. Using a laboratory-fabricated inhalation chamber, we found elevated urinary 3-HPMA, an acrolein metabolite, and increased acrolein adducts in the spinal cord after weeks of nasal exposure to acrolein at a concentration similar to that in tobacco smoke. The data indicated that acrolein is absorbed into the circulatory system and some enters the nervous system. It is expected that these findings may facilitate further studies to probe the pathological role of acrolein in the nervous system resulting from smoke and other external sources.

关键词： tobacco lipid peroxidation urine liquid chromatography mass spectrometry

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Elevated axonal membrane permeability and its correlation with motor deficits in an animal model of multiple sclerosis

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Translational Neurodegeneration 2017年第1期6卷 29-36页

作者： Gary Leung melissa tully Jonathan Tang Shengxi Wu Riyi Shi Department of Basic Medical Sciences College of Veterinary MedicinePurdue UniversityWest LafayetteIN 47907USA Weldon School of Biomedical Engineering Purdue UniversityWest LafayetteIN 47907USA MSTP program Indiana University School of MedicineIndianapolisINUSA Department of Neurobiology Fourth Military Medical UniversityXi’anChina

Background:It is increasingly clear that in addition to myelin disruption,axonal degeneration may also represent a key pathology in multiple sclerosis(MS).Hence,elucidating the mechanisms of axonal degeneration may not only enhance our understanding of the overall MS pathology,but also elucidate additional therapeutic *** objective of this study is assess the degree of axonal membrane disruption and its significance in motor deficits in EAE ***:Experimental Autoimmune Encephalomyelitis was induced in mice by subcutaneous injection of myelin oligodendrocyte glycoprotein/complete Freud’s adjuvant emulsion,followed by two intraperitoneal injections of pertussis *** assessment was performed using a 5-point *** Peroxidase Exclusion test was used to quantify the disruption of axonal *** glycol was prepared as a 30%(w/v)solution in phosphate buffered saline and injected ***:We have found evidence of axonal membrane disruption in EAE mice when symptoms peak and to a lesser degree,in the pre-symptomatic stage of EAE ***,polyethylene glycol(PEG),a known membrane fusogen,significantly reduces axonal membrane disruption in EAE *** PEG-mediated membrane repair was accompanied by significant amelioration of behavioral deficits,including a delay in the emergence of motor deficits,a delay of the emergence of peak symptom,and a reduction in the severity of peak ***:The current study is the first indication that axonal membrane disruption may be an important part of the pathology in EAE mice and may underlies behavioral *** study also presents the initial observation that PEG may be a therapeutic agent that can repair axolemma,arrest axonal degeneration and reduce motor deficits in EAE mice.

关键词： Multiple sclerosis EAE Axonal membrane damage Polyethylene glycol Acrolein Horseradish Peroxidase Membrane permeability Neurodegeneration

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DETECTION OF Ca^(2+)-DEPENDENT NEURONAL ACTIVITY SIMULTANEOUSLY WITH DYNAMIC CHANGES IN CEREBRAL BLOOD VOLUME AND TISSUE OXYGENATION FROM THE LIVE RAT BRAIN

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Journal of Innovative Optical Health Sciences 2009年第2期2卷 189-200页

作者： CONGWU DU ZHONGCHI LUO MEI YU HELENE BENVENISTE melissa tully RUBING PAN BRITTON CHANCE Medical Department Brookhaven National Laboratory UptonNY 11973-5000USA Department of Biomedical Engineering SUNY at Stony Brook Stony BrookNY 11794USA Department of Anesthesiology SUNY at Stony Brook Stony BrookNY 11794USA Department of Biology University of Illinois at Urbana-Champaign UrbanaIL 61801 Department of Biophysics and Physical Chemistry University of Pennsylvania PhiladelphiaPA19104

We present a catheter-based optical diffusion and fluorescence(ODF)probe to study the functional changes of the brain in *** ODF probe enables the simultaneous detection ofthe multi-wavelength absorbance and fluorescence emission from the living rat *** previous studies,including a transient stroke experiment of the rat brain as well as the brainresponse to cocaine,have established the feasibility of simultaneously determining changes incerebral blood volume(CBV),tissue oxygenation(StO2)and intracellular calcium([Ca^(2+)]i,using the fluorescence indicator Rhod2).Here,we present our preliminary results of somatosensory response to electrical forepaw stimulation obtained from the rat cortical brain by using theODF probe,which indicate that the probe could track brain activation by directly detecting[Ca^(2+)]i along with separately distinguishing CBV and StO2 in real *** changes of CBV,StO2 and[Ca^(2+)]i are comparable with the blood-oxygen-level-dependent(BOLD)response tothe stimulation obtained using functional magnetic resonance imaging(fMRI).However,thehigh temporal resolution of the optical methodology is advanced,thus providing a new modalityfor brain functional studies to understand the hemodynamic changes that underlie the neuronalactivity.

关键词： Optical spectroscopy calcium fluorescence Rhod2 labeling brain ischemia and cocaine addiction forepaw stimulation.

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Transepithelial leak in Barrett's esophagus patients: The role of proton pump inhibitors

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World Journal of Gastroenterology 2012年第22期18卷 2793-2797页

作者： Christopher Farrell melissa Morgan Owen tully Kevin Wolov Keith Kearney Benjamin Ngo Giancarlo Mercogliano James J Thornton Mary Carmen Valenzano James M Mullin Division of Gastroenterology Lankenau Hospital Wynnewood PA 19096 United States Lankenau Institute for Medical Research Wynnewood PA 19096 United States

AIM： To determine if the observed paracellular sucrose leak in Barrett＇s esophagus patients is due to their pro- ton pump inhibitor （PPI） use. METHODS： The in vivo sucrose permeability test was administered to healthy controls, to Barrett＇s patients and to non-Barrett＇s patients on continuous PPI thera- py. Degree of leak was tested for correlation with pres- ence of Barrett＇s, use of PPIs, and length of Barrett＇s segment and duration of PPI use. RESULTS： Barrett＇s patients manifested a near 3-fold greater, upper gastrointestinal sucrose leak than healthy controls. A decrease of sucrose leak was ob- served in Barrett＇s patients who ceased PPI use for 7 *** initial introduction of PPI use （in a PPI-na＇ive population） results in dramatic increase in sucrose leak, long-term, continuous PPI use manifested a slow spon- taneous decline in leak. The sucrose leak observed in Barrett＇s patients showed no correlation to the amount of Barrett＇s tissue present in the esophagus. CONCLUSION： Although future research is needed to determine the degree of paracellular leak in actual Barrett＇s mucosa, the relatively high degree of leak ob- served with in vivo sucrose permeability measurement of Barrett＇s patients reflects their PPI use and not their Barrett＇s tissue perse.

关键词： Barrett's esophagus Sucrose Tight junc-tion Paracellular, Omeprazole Proton pump inhibitor Transepithelial

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