503 research outputs found

    A mitochondria-targeted mass spectrometry probe to detect glyoxals: implications for diabetes

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    The glycation of protein and nucleic acids that occurs as a consequence of hyperglycaemia disrupts cell function and contributes to many pathologies, including those associated with diabetes and aging. Intracellular glycation occurs following the generation of the reactive 1,2-dicarbonyls methylglyoxal and glyoxal and disruption to mitochondrial function is associated with hyperglycemia. However, the contribution of these reactive dicarbonyls to mitochondrial damage in pathology is unclear due to uncertainties about their levels within mitochondria in cells and in vivo. To address this we have developed a mitochondria-targeted reagent (MitoG) designed to assess the levels of mitochondrial dicarbonyls within cells. MitoG comprises a lipophilic triphenylphosphonium cationic function, which directs the molecules to mitochondria within cells and an o-phenylenediamine moiety that reacts with dicarbonyls to give distinctive and stable products. The extent of accumulation of these diagnostic heterocyclic products can be readily and sensitively quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), enabling changes to be determined. Using the MitoG-based analysis we assessed the formation of methylglyoxal and glyoxal in response to hyperglycaemia in cells in culture and in the Akita mouse model of diabetes in vivo. These findings indicated that the levels of methylglyoxal and glyoxal within mitochondria increase during hyperglycaemia in both cells and in vivo, suggesting that they can contribute to the pathological mitochondrial dysfunction that occurs in diabetes and aging

    To wet or not to wet: that is the question

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    Wetting transitions have been predicted and observed to occur for various combinations of fluids and surfaces. This paper describes the origin of such transitions, for liquid films on solid surfaces, in terms of the gas-surface interaction potentials V(r), which depend on the specific adsorption system. The transitions of light inert gases and H2 molecules on alkali metal surfaces have been explored extensively and are relatively well understood in terms of the least attractive adsorption interactions in nature. Much less thoroughly investigated are wetting transitions of Hg, water, heavy inert gases and other molecular films. The basic idea is that nonwetting occurs, for energetic reasons, if the adsorption potential's well-depth D is smaller than, or comparable to, the well-depth of the adsorbate-adsorbate mutual interaction. At the wetting temperature, Tw, the transition to wetting occurs, for entropic reasons, when the liquid's surface tension is sufficiently small that the free energy cost in forming a thick film is sufficiently compensated by the fluid- surface interaction energy. Guidelines useful for exploring wetting transitions of other systems are analyzed, in terms of generic criteria involving the "simple model", which yields results in terms of gas-surface interaction parameters and thermodynamic properties of the bulk adsorbate.Comment: Article accepted for publication in J. Low Temp. Phy

    Equilibration and circulation of Red Sea Outflow water in the western Gulf of Aden

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    Author Posting. © American Meteorological Society, 2005. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 35 (2005): 1963–1985, doi:10.1175/JPO2787.1.Hydrographic, direct velocity, and subsurface float observations from the 2001 Red Sea Outflow Experiment (REDSOX) are analyzed to investigate the gravitational and dynamical adjustment of the Red Sea Outflow Water (RSOW) where it is injected into the open ocean in the western Gulf of Aden. During the winter REDSOX cruise, when outflow transport was large, several intermediate-depth salinity maxima (product waters) were formed from various bathymetrically confined branches of the outflow plume, ranging in depth from 400 to 800 m and in potential density from 27.0 to 27.5 σθ, a result of different mixing intensity along each branch. The outflow product waters were not dense enough to sink to the seafloor during either the summer or winter REDSOX cruises, but analysis of previous hydrographic and mooring data and results from a one-dimensional plume model suggest that they may be so during wintertime surges of strong outflow currents, or about 20% of the time during winter. Once vertically equilibrated in the Gulf of Aden, the shallowest RSOW was strongly influenced by mesoscale eddies that swept it farther into the gulf. The deeper RSOW was initially more confined by the walls of the Tadjura Rift, but eventually it escaped from the rift and was advected mainly southward along the continental slope. There was no evidence of a continuous boundary undercurrent of RSOW similar to the Mediterranean Undercurrent in the Gulf of Cadiz. This is explained by considering 1) the variability in outflow transport and 2) several different criteria for separation of a jet at a sharp corner, which indicate that the outflow currents should separate from the boundary where they are injected into the gulf.This work was supported by the U.S. National Science Foundation under Grants OCE-9818464 (WHOI) and OCE-9819506 (RSMAS)

    Rosiglitazone as an option for patients with acromegaly: a case series

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    <p>Abstract</p> <p>Introduction</p> <p>In the patient with acromegaly, pituitary surgery is the therapeutic standard. Despite undergoing surgery, a significant number of patients with acromegaly continue to have uncontrolled growth hormone secretion. These patients require other treatments such as external irradiation and/or drug therapy.</p> <p>Case presentation</p> <p>We present the clinical and laboratory responses to six months of treatment with rosiglitazone in four cases. In all four cases, the patients had persistent growth hormone overproduction despite previous surgical treatment and other conventional therapy. Case 1 is a 57-year-old Caucasian woman, case 2 is a 51-year-old Hispanic man, case 3 is a 32-year-old Hispanic woman, and case 4 is a 36-year-old Hispanic man. In three of these patients, basal and nadir growth hormone and insulin-like growth factor 1 levels were significantly decreased (<it>P </it>< 0.05 and <it>P </it>< 0.01, respectively).</p> <p>Conclusion</p> <p>Rosiglitazone could be a treatment option in select patients with acromegaly.</p

    Perceptions of animal physiotherapy amongst Irish veterinary surgeons

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    The aim of this study was to investigate veterinary surgeons' perceptions, knowledge and use of animal physiotherapy in the Republic of Ireland. A questionnaire was developed and sent to 200 veterinary surgeons, of which 97 were returned. Results indicated that 77 (79%) of respondents were aware of animal physiotherapists. Common sources of information included veterinary colleagues, owners and professional journals, with physiotherapists themselves and undergraduate training being less commonly cited. Awareness of animal physiotherapy was greatest amongst those working in equine practice (χ2 = 5.7, df 1, p = 0.017); they were more knowledgeable about its techniques (t = 2.806, df 75, p = 0.006) and more likely to refer (χ2 = 48.36, df 1, p = 0.0001). Seventy-four respondents (96%) thought that more research was necessary to increase the evidence base for animal physiotherapy. If this branch of physiotherapy is to develop, there needs to be increased interaction and co-operation between veterinary surgeons and chartered animal physiotherapists

    Third-Party Allogeneic Mesenchymal Stromal Cells Prevent Rejection in a Pre-sensitized High-Risk Model of Corneal Transplantation

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    High-risk cornea transplant recipients represent a patient population with significant un-met medical need for more effective therapies to prevent immunological graft rejection due to heightened anti-donor immune response. In this study, a rat model of pre-existing anti-donor immunity was developed in which corneal allografts were rejected earlier than in non-pre-sensitized recipients. In this model, third-party (non-donor, non-recipient strain) allogeneic mesenchymal stromal cells (allo-MSC) were administered intravenously 7 and 1 days prior to transplantation. Rejection-free graft survival to 30 days post-transplant improved from 0 to 63.6% in MSC-treated compared to vehicle-treated control animals (p = &lt; 0.0001). Pre-sensitized animals that received third-party allo-MSC prior to transplantation had significantly higher proportions of CD45+CD11b+ B220+ monocytes in the lungs 24 h after the second MSC injection and significantly higher proportions of CD4+ FoxP3+ regulatory T cells in the graft-draining lymph nodes at the average day of rejection of control animals. In in vitro experiments, third-party allo-MSC polarized primary lung-derived CD11b/c+ myeloid cells to a more anti-inflammatory phenotype, as determined by cytokine profile and conferred them with the capacity to suppress T cell activation via prostaglandin E2 and TGFβ1. In experiments designed to further validate the clinical potential of the protocol, thawed cryopreserved, third-party allo-MSC were shown to be similarly potent at prolonging rejection-free corneal allograft survival as their freshly-cultured counterparts in the pre-sensitized high-risk model. Furthermore, thawed cryopreserved third-party allo-MSC could be co-administered with mycophenolate mofetil without adversely affecting their immunomodulatory function. In conclusion, a clinically-relevant protocol consisting of two intravenous infusions of third-party allo-MSC during the week prior to transplantation, exerts a potent anti-rejection effect in a pre-sensitized rat model of high-risk corneal allo-transplantation. This immune regulatory effect is likely to be mediated in the immediate post-transplant period through the promotion, by allo-MSC, of alternatively-activated macrophages in the lung and, later, by enhanced regulatory T-cell numbers

    The prevention of contrast induced nephropathy by sarpogrelate in patients with chronic kidney disease: a study protocol for a prospective randomized controlled clinical trial

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    <p>Abstract</p> <p>Background</p> <p>Contrast-induced nephropathy (CIN) is a serious clinical problem associated with increased morbidity and mortality, particularly in patients with chronic renal insufficiency. Although some agents including hydration with saline are being prescribed to prevent renal deterioration in these high risk patients, their efficacy is not clearly defined and debatable. Therefore additional prophylactic pretreatments are needed.</p> <p>Methods/Design</p> <p>The present study aims to investigate differences in occurrence of CIN after sarpogrelate premedication in patients with chronic kidney disease (CKD). 268 participants, aged 20-85 years with a clinical diagnosis of CKD will be recruited. They will be randomly allocated to one of two conditions: (i) routine treatment without sarpogrelate, and (ii) routine treatment with sarpogrelate (a fixed-flexible dose of 300 mg/day). The primary outcome is the occurrence of CIN during 4 weeks after receiving contrast agent.</p> <p>Discussion</p> <p>As of May 2010, there were no registered trials evaluating the therapeutic potentials of sarpogrelate in preventing for CIN. If sarpogrelate decreases the worsening of renal function and occurrence of CIN, it will provide a safe, easy and inexpensive treatment option.</p> <p>Trial registration</p> <p>NCT01165567</p
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