The University of Arkansas for Medical science is part of the University of Arkansas System, a state-run university in the U.S. state of Arkansas. The main campus is located in Little Rock and consists of five colleges including one graduate school, seven institutes, a statewide network of community educational centers, and the UAMS Medical Center. Wikipedia.
Hinson J.A.,University of Arkansas for Medical Sciences
Handbook of Experimental Pharmacology | Year: 2010
Although considered safe at therapeutic doses, at higher doses, acetaminophen produces a centrilobular hepatic necrosis that can be fatal. Acetaminophen poisoning accounts for approximately one-half of all cases of acute liver failure in the United States and Great Britain today. The mechanism occurs by a complex sequence of events. These events include: (1) CYP metabolism to a reactive metabolite which depletes glutathione and covalently binds to proteins; (2) loss of glutathione with an increased formation of reactive oxygen and nitrogen species in hepatocytes undergoing necrotic changes; (3) increased oxidative stress, associated with alterations in calcium homeostasis and initiation of signal transduction responses, causing mitochondrial permeability transition; (4) mitochondrial permeability transition occurring with additional oxidative stress, loss of mitochondrial membrane potential, and loss of the ability of the mitochondria to synthesize ATP; and (5) loss of ATP which leads to necrosis. Associated with these essential events there appear to be a number of inflammatory mediators such as certain cytokines and chemokines that can modify the toxicity. Some have been shown to alter oxidative stress, but the relationship of these modulators to other critical mechanistic events has not been well delineated. In addition, existing data support the involvement of cytokines, chemokines, and growth factors in the initiation of regenerative processes leading to the reestablishment of hepatic structure and function. © 2010 Springer-Verlag Berlin Heidelberg.
Usmani S.Z.,University of Arkansas for Medical Sciences
Blood | Year: 2013
Lenalidomide has been linked to myelodysplastic syndrome (MDS) after autotransplants for myeloma. Total therapy trials (TT; TT2(-/+) thalidomide) and TT3 (TT3a with bortezomib, thalidomide; TT3b with additional lenalidomide) offered the opportunity to examine the contribution of these immune-modulatory agents to MDS-associated cytogenetic abnormalities (MDS-CA) and clinical MDS or acute leukemia ("clinical MDS/AL"). Of 1080 patients with serial cytogenetic studies, MDS-CA occurred in 11% and clinical MDS/AL in 3%. Risk features of MDS-CA included TT3b, age ≥65 years, male gender, levels of β-2-microglobulin >5.5 mg/L, and multiple myeloma relapse. Clinical MDS/AL occurred less frequently in the control arm of TT2 and more often with TT3a and TT3b. Since MDS-CA often antedated clinical disease, periodic cytogenetic monitoring is recommended. Larger CD34 quantities should be collected upfront as the risk of MDS could be reduced by applying higher CD34 doses with transplant. Thus, treatment, host, and myeloma features could be linked to MDS development after therapy for this malignancy. This trial was registered at www.clinicaltrials.gov: TT3A: NCT00081939, TT3B: NCT00572169.
Jilka R.L.,University of Arkansas for Medical Sciences
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2013
Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized. © 2013 Published by Oxford University Press on behalf of the Gerontological Society of America 2013.
Manolagas S.C.,University of Arkansas for Medical Sciences
Endocrine Reviews | Year: 2010
Estrogen deficiency has been considered the seminal mechanism of osteoporosis in both women and men, but epidemiological evidence in humans and recent mechanistic studies in rodents indicate that aging and the associated increase in reactive oxygen species (ROS) are the proximal culprits. ROS greatly influence the generation and survival of osteoclasts, osteoblasts, and osteocytes. Moreover, oxidative defense by the FoxO transcription factors is indispensable for skeletal homeostasis at any age. Loss of estrogens or androgens decreases defense against oxidative stress in bone, and this accounts for the increased bone resorption associated with the acute loss of these hormones. ROS-activated FoxOs in early mesenchymal progenitors also divert β-catenin away from Wnt signaling, leading to decreased osteoblastogenesis. This latter mechanism may be implicated in the pathogenesis of type 1 and 2 diabetes and ROS-mediated adverse effects of diabetes on bone formation. Attenuation of Wnt signaling by the activation of peroxisome proliferator-activated receptor γ by ligands generated from lipid oxidation also contributes to the age-dependent decrease in bone formation, suggesting a mechanistic explanation for the link between atherosclerosis and osteoporosis. Additionally, increased glucocorticoid production and sensitivity with advancing age decrease skeletal hydration and thereby increase skeletal fragility by attenuating the volume of the bone vasculature and interstitial fluid. This emerging evidence provides a paradigm shift from the "estrogen-centric" account of the pathogenesis of involutional osteoporosis to one in which age-related mechanisms intrinsic to bone and oxidative stress are protagonists and age-related changes in other organs and tissues, such as ovaries, accentuate them. Copyright © 2010 by The Endocrine Society.
Collins II R.T.,University of Arkansas for Medical Sciences
Circulation | Year: 2013
WS is a complex, multisystem disorder with significant cardiovascular manifestations. Arterial stenoses make up the large majority of cardiovascular issues in patients with WS. Although all patients with WS need early and ongoing cardiovascular evaluation and follow-up, most patients will not require cardiovascular interventions. In those patients who do undergo surgical and catheter-based interventions, the results are favorable, although long-segment STA remains very difficult to treat. Sudden death in patients with WS is significantly greater than in the general population, and expert periprocedural care of these patients is paramount. Prolongation of the QTc is common in patients with WS, and conservative management with medications should be considered. The potential for groundbreaking advancements in medical therapies is present in already available pharmaceutical agents; these potential therapies need to be investigated in meaningful ways. © 2013 American Heart Association, Inc.
Dienel G.A.,University of Arkansas for Medical Sciences
Journal of Cerebral Blood Flow and Metabolism | Year: 2012
Potential roles for lactate in the energetics of brain activation have changed radically during the past three decades, shifting from waste product to supplemental fuel and signaling molecule. Current models for lactate transport and metabolism involving cellular responses to excitatory neurotransmission are highly debated, owing, in part, to discordant results obtained in different experimental systems and conditions. Major conclusions drawn from tabular data summarizing results obtained in many laboratories are as follows: Glutamate-stimulated glycolysis is not an inherent property of all astrocyte cultures. Synaptosomes from the adult brain and many preparations of cultured neurons have high capacities to increase glucose transport, glycolysis, and glucose-supported respiration, and pathway rates are stimulated by glutamate and compounds that enhance metabolic demand. Lactate accumulation in activated tissue is a minor fraction of glucose metabolized and does not reflect pathway fluxes. Brain activation in subjects with low plasma lactate causes outward, brain-to-blood lactate gradients, and lactate is quickly released in substantial amounts. Lactate utilization by the adult brain increases during lactate infusions and strenuous exercise that markedly increase blood lactate levels. Lactate can be an opportunistic, glucose-sparing substrate when present in high amounts, but most evidence supports glucose as the major fuel for normal, activated brain. © 2012 ISCBFM All rights reserved.
Zharov V.P.,University of Arkansas for Medical Sciences
Nature Photonics | Year: 2011
High-resolution nonlinear laser spectroscopy based on absorption saturation, Lamb-dip and spectral hole-burning phenomena has contributed much to basic and applied photonics. Here, a laser spectroscopy based on nonlinear nanobubble-related photothermal and photoacoustic phenomena is presented. It shows ultrasharp resonances and dips up to a few nanometres wide in broad plasmonic spectra of nanoparticles. It also demonstrates narrowing of absorption spectra of dyes and cellular chromophores, as well as an increase in the sensitivity and resolution of the spectral hole-burning technique. This approach can permits the study of nonlinear plasmonics at a level of resolution beyond the spectral limits, the identification of weakly absorbing spectral holes, spectral optimization of photothermal nanotherapy, measurements of tiny red and blue resonance shifts in nanoplasmonic sensors, the use of negative contrast in photoacoustic technique, multispectral imaging and multicolour cytometry. © 2011 Macmillan Publishers Limited. All rights reserved.
University of Arkansas for Medical Sciences | Date: 2016-08-18
A device and method of using the device to detect the presence and composition of clots and other target objects in a circulatory vessel of a living subject is described. In particular, devices and methods of detecting the presence and composition of clots and other target objects in a circulatory vessel of a living subject using in vivo photoacoustic flow cytometry techniques is described.
Agency: NSF | Branch: Continuing grant | Program: | Phase: INSTRUMENTAT & INSTRUMENT DEVP | Award Amount: 293.38K | Year: 2016
An award is made to the University of Arkansas for Medical Sciences to develop a far-field super resolution photothermal nanoscope (PTN) for three-dimensional, label-free imaging of weakly fluorescent cellular nanostructures and nanoparticles that is currently not possible. Applications of PTN will include high-resolution imaging of molecules in live cells as well as investigating protein misfolding, degradation, and aggregation. PTN can provide control and optimization of biological applications of lasers such as tissue dissection and ablation. PTN would be a valuable alternative or supplement to existing microscopic techniques and, in combination with them, could provide a powerful and versatile tool for biological research with a focus on cells. The project will benefit variety of biological research communities and scientific areas including cell biology, proteomics, neuroscience, nanotechnology, plasmonic nanosensing, gerontology, and cancer therapy. This interdisciplinary research involving physicists, biologists, and computer engineers includes a training program on advanced optical imaging that will train and educate undergraduate and graduate students from underrepresented groups.
This project has the following goals: 1) develop a photothermal confocal nanosocopy platform with enhanced sensitivity; 2) explore nonlinear and photoswitching phenomena to improve both spatial and spectral resolution; and 3) explore the unique applications of PTN including label-free and targeted imaging of different nanostructures, protein aggregates and image-guided disaggregation. The intellectual merit of the project lies in the new concept of a far-field microscopy integrating a confocal design, high pulse-rate lasers, high-speed scanning, and time-resolved detection, to significantly improve on current diffraction and spectral limitations. Because many cellular components in the native state have low fluorescence, and are nano-scale in size, there is a clear need for an imaging technique to study them with high resolution, high absorption sensitivity, temporal resolution and fast acquisition time. The proposed PTN will provide unprecedented resolution with enhanced absorption sensitivity, thus opening new windows into unexplored areas of biological research associated with cell metabolic activity, oxidization, endocytosis, phagocytosis, melanogenesis, and apoptosis.
Weinstein R.S.,University of Arkansas for Medical Sciences
New England Journal of Medicine | Year: 2011
A 55-year-old woman with severe, persistent asthma requiring glucocorticoid therapy for the past 3 months presents for care. Her medications include albuterol, inhaled fluticasone with salmeterol, montelukast, and prednisone (at a dose of 10 mg per day). In the past, she received several intermittent courses of prednisone at a dose of 15 mg or more per day. Her weight is 45.5 kg (100 lb), and her height 157.5 cm (62 in.); the body-mass index (the weight in kilograms divided by the square of the height in meters) is 18. Scattered wheezing is heard during expiration. Findings on vertebral percussion and rib-cage compression are unremarkable. How should her case be evaluated and managed to minimize the risk of fractures? Copyright © 2011 Massachusetts Medical Society.