Research and Development Service

Isle of Wight, VA, United States

Research and Development Service

Isle of Wight, VA, United States
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Cabral P.,Prof Doutor Fernando Fonseca Hospital Ic | Paulino C.,University of Coimbra | Clopton P.,Research and Development Service | Resnick D.,University of San Diego
Skeletal Radiology | Year: 2013

Objective: To determine if a statistical association exists between abnormalities in one ankle tendon group (i.e., peroneal, medial flexor, or Achilles) and those in another. Materials and methods: A retrospective analysis of 1.5-T and 3-T MR ankle examinations in 100 patients conducted between November 1, 2011 and April 1, 2012 was performed. The cross-sectional areas and diameters of the ankle tendons - Achilles (ACH), peroneus brevis (PB) and longus (PL), tibialis posterior (TP), flexor digitorum longus (FDL), and flexor hallux longus (FHL) - were measured, and the results were correlated to determine any association with the presence of qualitative abnormalities (tenosynovitis, tendinosis, and tendon tearing). Results: Subjects with larger diameters of the ACH tendon also revealed larger PL, TP, FDL, and FHL tendon diameters and sectional areas. Furthermore, subjects with larger PL tendons generally revealed larger flexor tendons and the same was also true when medial compartment tendons were individually assessed and measurements compared among the three of them. There was a statistically significant association with regard to the presence of tendon abnormalities (tendinosis, tenosynovitis, and tearing) in both the peroneal and medial flexor tendons. The presence of an abnormality in the ACH tendon correlated strongly with increasing diameters and areas of all the other ankle tendons except for the PB tendon. Conclusions: There is an association between quantitative and qualitative abnormalities of one group of tendons when compared with the others with respect to the ACH, medial flexor, and peroneal tendons of the ankle, which is perhaps explained by a retinacular and fascial complex that anatomically connects the three groups. © 2013 The Author(s).


Elder G.A.,Neurology Service | Elder G.A.,Mount Sinai School of Medicine | Gama Sosa M.A.,Research and Development Service | Gama Sosa M.A.,Mount Sinai School of Medicine | And 2 more authors.
Mount Sinai Journal of Medicine | Year: 2010

Alzheimer's disease is the most common cause of senile dementia in the United States and Europe. At present, there is no effective treatment. Given the disease's prevalence and poor prognosis, the development of animal models has been a high research priority. Transgenic modeling has been pursued on the basis of the amyloid hypothesis and has taken advantage of mutations in the amyloid precursor protein and the presenilins that cause familial forms of Alzheimer's disease. Modeling has been most aggressively pursued in mice, for which the techniques of genetic modification are well developed. Transgenic mouse models now exist that mimic a range of Alzheimer's disease-related pathologies. Although none of the models fully replicates the human disease, the models have contributed significant insights into the pathophysiology of β-amyloid toxicity, particularly with respect to the effects of different β-amyloid species and the possible pathogenic role of β-amyloid oligomers. They have also been widely used in the preclinical testing of potential therapeutic modalities and have played a pivotal role in the development of immunotherapies for Alzheimer's disease that are currently in clinical trials. These models will, without a doubt, continue to play central roles in preclinical testing and be used as tools for developing insights into the biological basis of Alzheimer's disease. © 2010 Mount Sinai School of Medicine.


News Article | February 15, 2017
Site: www.prweb.com

The VA Maryland Health Care System and the University of Maryland Fischell Department of Bioengineering are collaborating on a research project focused on multiple sclerosis (MS). Led by Christopher M. Jewell, PhD, an assistant professor in bioengineering, the project seeks to use nanotechnology to control the disease without compromising normal immune function that often occurs during autoimmune diseases. Ultimately the team hopes this pre-clinical research could contribute to reducing cost and burden of disease for MS patients and their families. Funded by the VA’s Office of Research and Development, Biomedical Laboratory Research and Development Service as a VA Merit Award--the first given to a University of Maryland College Park faculty member--the four-year, $1.1 million project is titled, “Tunable assembly of regulatory immune signals to promote myelin-specific tolerance.” The project will explore strategies that could control MS with a vaccine-like specificity that keeps the rest of the immune system functional. Currently, conventional treatments for MS often compromise the immune system, leaving patients vulnerable to infection. MS—for which there is no cure-- occurs when a patient’s immune system mistakenly attacks myelin in the brain, leading to slow loss of mobility over decades. “We are thrilled that Dr. Jewell will be joining the VA Maryland Research and Development Service,” said Thomas Hornyak, MD, PhD, associate chief staff for Research and Development at the VA Maryland Health Care System. “His study merges immunology, bioengineering, and chemistry, and presents an exciting new direction for biomedical research at our facility,” he added. Importantly, several pre-clinical reports and clinical trials have investigated the idea that co-administration of myelin peptide and tolerizing immune signals to lymph node tissues that coordinate immune response can promote the development of regulatory T cells (TREGS) that ameliorate disease. “This research will study a new idea to promote TREGS that control disease and importantly, test the idea in both pre-clinical models and in samples from human MS patients,” said Jewell, who will soon be a part of the VA Maryland Health Care System’s Research and Development Service. “One of the most exciting aspects is our multidisciplinary team that brings together engineers, clinicians, and immunologists from the VA, the University of Maryland College Park, and the University of Maryland, Baltimore. This will allow us to design new materials and test them in both pre-clinical models, and in samples from human MS patients. We hope the project will shed new light on some of the mechanisms of autoimmunity, and contribute to more specific and long-lasting treatment options for veterans that also reduce the financial burden on veterans and their families," he added. Thus, this research project could lead to permanent improvements for MS patients, improvements that could greatly reduce health care costs for them and their families. “This latest collaborative effort to advance multiple sclerosis research demonstrates how critical it is that engineers work together with fellow scientists and clinicians to create solutions to today’s most pressing health challenges,” said Darryll J. Pines, dean of the University of Maryland A. James Clark School of Engineering. The project also fosters interdisciplinary collaborations between other team members, including Dr. Walter Royal, MD, at the VA Multiple Sclerosis Center of Excellence located at the Baltimore VA Medical Center and with Dr. Jonathan Bromberg, MD/PhD, at the University of Maryland Medical School in Baltimore. “The potential outcomes of this research can bring lasting improvements to lives of veterans struggling with MS and to their families, who often serve as caregivers," said Dr. Adam Robinson, director of the VA Maryland Health Care System. “MS is a debilitating disease over time, and we’re excited that Dr. Jewell and his team are pushing forward with a project that can positively impact large numbers of veterans.” In collaboration with an array of academic centers such as University of Maryland, College Park and the University of Maryland School of Medicine, the VA Maryland Health Care System conducts a range of science and medical research projects, from basic science to clinical and rehabilitative medicine, totaling about $27 million annually. The VA Maryland Health Care System (VAMHCS) provides a broad spectrum of medical, surgical, rehabilitative, mental health and outpatient care to veterans at two medical centers, one rehabilitation & extended care center and five outpatient clinics located throughout the state. More than 52,000 veterans from various generations receive care from VAMHCS annually. Nationally recognized for its state-of-the-art technology and quality patient care, VAMHCS is proud of its reputation as a leader in veterans’ health care, research and education. It costs nothing for Veterans to enroll for health care with the VA Maryland Health Care System and it could be one of the more important things a Veteran can do. For information about VA health care eligibility and enrollment or how to apply for a VA medical care hardship to avoid future copayments for VA health care, interested Veterans are urged to call the Enrollment Center for the VA Maryland Health Care System, Monday through Friday, from 8 a.m. to 4:30 p.m. at 1-800-463-6295, ext. 7324 or visit http://www.maryland.va.gov.


Stolzmann K.L.,Research and Development Service | Stolzmann K.L.,Harvard University | Gagnon D.R.,Research and Development Service | Gagnon D.R.,Boston University | And 8 more authors.
American Journal of Physical Medicine and Rehabilitation | Year: 2010

OBJECTIVE:: Chest illnesses commonly cause morbidity in persons with chronic spinal cord injury. Risk factors remain poorly characterized because previous studies have not accounted for factors other than spinal cord injury. DESIGN:: Between 1994 and 2005, 403 participants completed a respiratory questionnaire and underwent spirometry. Participants were contacted at a median of 1.7 yrs [interquartile range: 1.3-2.5 yrs] apart over a mean (SD) of 5.1 ± 3.0 yrs and asked to report chest illnesses that had resulted in time off work, spent indoors, or in bed since prior contact. RESULTS:: In 97 participants, there were 247 chest illnesses (0.12/person-year) with 54 hospitalizations (22%). Spinal cord injury level, completeness of injury, and duration of injury were not associated with illness risk. Adjusting for age and smoking history, any wheeze (relative risk = 1.92; 95% confidence interval: 1.19, 3.08), pneumonia or bronchitis since spinal cord injury (relative risk = 2.29; 95% confidence interval: 1.40, 3.75), and physician-diagnosed chronic obstructive pulmonary disease (relative risk = 2.17; 95% confidence interval: 1.08, 4.37) were associated with a greater risk of chest illness. Each percent-predicted decrease in forced expiratory volume in 1 sec was associated with a 1.2% increase in risk of chest illness (P = 0.030). CONCLUSIONS:: In chronic spinal cord injury, chest illness resulting in time spent away from usual activities was not related to the level or completeness of spinal cord injury but was related to reduced pulmonary function, wheeze, chronic obstructive pulmonary disease, a history of pneumonia and bronchitis, and smoking. Copyright © 2010 by Lippincott Williams & Wilkins.


Sosa M.A.G.,Research and Development Service | Sosa M.A.G.,Mount Sinai School of Medicine | De Gasperi R.,Research and Development Service | De Gasperi R.,Mount Sinai School of Medicine | Elder G.A.,Mount Sinai School of Medicine
Human Genetics | Year: 2012

Transgenic systems are widely used to study the cellular and molecular basis of human neurodegenerative diseases. A wide variety of model organisms have been utilized, including bacteria (Escherichia coli), plants (Arabidopsis thaliana), nematodes (Caenorhabditis elegans), arthropods (Drosophila melanogaster), Wsh (zebraWsh, Danio rerio), rodents (mouse, Mus musculus and rat, Rattus norvegicus) as well as non-human primates (rhesus monkey, Macaca mulatta). These transgenic systems have enormous value for understanding the pathophysiological basis of these disorders and have, in some cases, been instrumental in the development of therapeutic approaches to treat these conditions. In this review, we discuss the most commonly used model organisms and the methodologies available for the preparation of transgenic organisms. Moreover, we provide selected examples of the use of these technologies for the preparation of transgenic animal models of neurodegenerative diseases, including Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Parkinson's disease (PD) and discuss the application of these technologies to AD as an example of how transgenic modeling has affected the study of human neurodegenerative diseases. © Springer-Verlag (outside the USA) 2011.


Patel S.,Research and Development Service | Alex Grizzell J.,Research and Development Service | Alex Grizzell J.,University of South Florida | Holmes R.,Research and Development Service | And 11 more authors.
Frontiers in Aging Neuroscience | Year: 2014

Alzheimer's disease (AD) is associated with cognitive and non-cognitive symptoms for which there are currently no effective therapies. We have previously reported that cotinine, a natural product obtained from tobacco leaves, prevented memory loss and diminished amyloid-β (Aβ) plaque pathology in transgenic 6799 mice (Tg6799 mice) when treated prior to the development of the pathology. We have also shown that cotinine reduces depressive-like behavior in normal and chronically stressed C57BL/6 mice. Here, we extend our previous studies by investigating the effects of cotinine on the progression of AD-like pathology, depressive-like behavior, and the mechanisms underlying its beneficial effects in Tg6799 mice when left untreated until after a more advanced stage of the disease's development. The results show that vehicle-treated Tg6799 mice displayed an accentuated loss of working memory and an abundant Aβ plaque pathology that were accompanied by higher levels of depressive-like behavior as compared to control littermates. By contrast, prolonged daily cotinine treatment to Tg6799 mice, withheld until after a mid-level progression of AD-like pathology, reduced Aβ levels/plaques and depressive-like behavior. Moreover, this treatment paradigm dramatically improved working memory as compared to control littermates. The beneficial effects of cotinine were accompanied by an increase in the expression of the active form of protein kinase B and the postsynaptic density protein 95 in the hippocampi and frontal cortices of Tg6799 mice. This suggests that cotinine halts the progression of AD-like pathology while reducing depressive-like behavior by stimulating signaling pathways supporting synaptic plasticity in Tg6799 mice. The potential use of cotinine to treat cognitive and non-cognitive symptoms of AD is discussed. © 2014 Patel, Grizzel, Holmes, Zeitlin, Solomon, Sutton, Rohani, Charry, Iarkov, Mori and Echeverria_moran.


Grizzell J.A.,Research and Development Service | Grizzell J.A.,University of South Florida | Iarkov A.,Research and Development Service | Holmes R.,Research and Development Service | And 5 more authors.
Behavioural Brain Research | Year: 2014

Chronic stress underlies and/or exacerbates many psychiatric conditions and often results in memory impairment as well as depressive symptoms. Such afflicted individuals use tobacco more than the general population and this has been suggested as a form of self-medication. Cotinine, the predominant metabolite of nicotine, may underlie such behavior as it has been shown to ameliorate anxiety and memory loss in animal models. In this study, we sought to investigate the effects of cotinine on working memory and depressive-like behavior in mice subjected to prolonged restraint. Cotinine-treated mice displayed better performance than vehicle-treated cohorts on the working memory task, the radial arm water maze test. In addition, with or without chronic stress exposure, cotinine-treated mice engaged in fewer depressive-like behaviors as assessed using the tail suspension and Porsolt's forced swim tests. These antidepressant and nootropic effects of cotinine were associated with an increase in the synaptophysin expression, a commonly used marker of synaptic density, in the hippocampus as well as the prefrontal and entorhinal cortices of restrained mice. The beneficial effects of cotinine in preventing various consequences of chronic stress were underscored by the inhibition of the glycogen synthase kinase 3 β in the hippocampus and prefrontal cortex. Taken together, our results show for the first time that cotinine reduces the negative effects of stress on mood, memory, and the synapse. © 2014.


Grizzell J.A.,Research and Development Service | Grizzell J.A.,University of South Florida | Mullins M.,Research and Development Service | Iarkov A.,Research and Development Service | And 7 more authors.
Behavioral Neuroscience | Year: 2014

Cotinine, the predominant metabolite of nicotine, appears to act as an antidepressant. We have previously shown that cotinine reduced immobile postures in Porsolt's forced swim (FS) and tail suspension tests while preserving the synaptic density in the hippocampus as well as prefrontal and entorhinal cortices of mice subjected to chronic restraint stress. In this study, we investigated the effect of daily oral cotinine (5 mg/kg) on depressive-like behavior induced by repeated, FS stress for 6 consecutive days in adult, male C57BL/6J mice. The results support our previous report that cotinine administration reduces depressive-like behavior in mice subjected or not to high salience stress. In addition, cotinine enhanced the expression of the vascular endothelial growth factor (VEGF) in the hippocampus of mice subjected to repetitive FS stress. Altogether, the results suggest that cotinine may be an effective antidepressant positively influencing mood through a mechanism involving the preservation of brain homeostasis and the expression of critical growth factors such as VEGF.


PubMed | Research and Development Service
Type: Journal Article | Journal: Human genetics | Year: 2012

Transgenic systems are widely used to study the cellular and molecular basis of human neurodegenerative diseases. A wide variety of model organisms have been utilized, including bacteria (Escherichia coli), plants (Arabidopsis thaliana), nematodes (Caenorhabditis elegans), arthropods (Drosophila melanogaster), fish (zebrafish, Danio rerio), rodents (mouse, Mus musculus and rat, Rattus norvegicus) as well as non-human primates (rhesus monkey, Macaca mulatta). These transgenic systems have enormous value for understanding the pathophysiological basis of these disorders and have, in some cases, been instrumental in the development of therapeutic approaches to treat these conditions. In this review, we discuss the most commonly used model organisms and the methodologies available for the preparation of transgenic organisms. Moreover, we provide selected examples of the use of these technologies for the preparation of transgenic animal models of neurodegenerative diseases, including Alzheimers disease (AD), frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), Huntingtons disease (HD) and Parkinsons disease (PD) and discuss the application of these technologies to AD as an example of how transgenic modeling has affected the study of human neurodegenerative diseases.


PubMed | Research and Development Service
Type: Journal Article | Journal: Behavioral neuroscience | Year: 2014

Cotinine, the predominant metabolite of nicotine, appears to act as an antidepressant. We have previously shown that cotinine reduced immobile postures in Porsolts forced swim (FS) and tail suspension tests while preserving the synaptic density in the hippocampus as well as prefrontal and entorhinal cortices of mice subjected to chronic restraint stress. In this study, we investigated the effect of daily oral cotinine (5 mg/kg) on depressive-like behavior induced by repeated, FS stress for 6 consecutive days in adult, male C57BL/6J mice. The results support our previous report that cotinine administration reduces depressive-like behavior in mice subjected or not to high salience stress. In addition, cotinine enhanced the expression of the vascular endothelial growth factor (VEGF) in the hippocampus of mice subjected to repetitive FS stress. Altogether, the results suggest that cotinine may be an effective antidepressant positively influencing mood through a mechanism involving the preservation of brain homeostasis and the expression of critical growth factors such as VEGF. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

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