| Department of Transportation Inhalation Test of Neutralized GB Hydrolysate in Sprague-Dawley Rats |
May-2009 |
21 pages |
| Authors:
William T Jr; Muse; Charles L Crouse; Ronald A Evans; EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD RESEARCH AND TECHNOLOGY DIR
|
 | The Assembled Chemical Weapons Alternatives (ACWA) Program has been tasked to demonstrate alternative technologies that will safely dispose of assembled chemicals munitions through means other than incineration. The ACWA program is currently investigating GB hydrolysate, a product solution resulting from chemically neutralizing GB with aqueous sodium hydroxide (pH 12.8) as an acceptably treated waste that can be transported offsite for secondary treatment. An acute inhalation toxicity test was conducted on ... |
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| Molecular Connections Between Arousal and Metabolic Disease: Orexin and Modafinil |
Apr-2009 |
19 pages |
| Authors:
Stephen C Benoit; CINCINNATI UNIV OH
|
| Metabolic diseases are known to be tightly linked to arousal-sleep cycles and impact cognitive function. Importantly, the armed forces represent a population at significant risk for increased stress and disrupted arousal-sleep cycles. Because the incidence of metabolic disease and obesity is increasing, even in these physically fit individuals, understanding the interactions between these systems is highly significant. Further, some anti-fatigue pharmacologies (e.g.,modafinil) are already used in military settings, though their ... |
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| Carcinogenicity of Embedded Tungsten Alloys in Mice |
Mar-2009 |
27 pages |
| Authors:
John F Kalinich; JACKSON (HENRY M) FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE ROCKVILLE MD
|
| A variety of unique metal mixtures have entered the military arsenals of many countries in recent years. One such material is the tungsten alloys, which have been proposed as replacements for depleted uranium (DU) in armor-penetrating munitions. As a result, opportunities for exposure are increasingly likely. This leads to questions, similar to those originally surrounding DU, as to the health effects of exposure to the tungsten alloys, especially for embedded ... |
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| Pharmacological Prevention and Reversion of Erectile Dysfunction After Radical Prostatectomy, by Modulation of Nitric Oxide/cGMP Pathways |
Mar-2009 |
65 pages |
| Authors:
Nestor F Gonzalez-Cadavid; CHARLES DREW UNIV LOS ANGELES CA
|
| During Year 2 an experimental article previously submitted was completed and extensively revised for its ulterior recent publication (P-1), describing the time course of histological and functional changes affecting the penile corpora cavernosa after bilateral cavernosal nerve resection (BCNR) in the rat, as an experimental model for erectile dysfunction subsequent to radical prostatectomy for prostate cancer. This condition seriously affects the quality of life of a large fraction of male ... |
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| Sensors to Assess Pressure-Mediated Effects on Blast-Induced Traumatic Brain Injury |
Mar-2009 |
10 pages |
| Authors:
Mikulas Chavko; NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
|
| This study was designed to investigate the contributions of direct impact of blast on the skull in two different orientations: face-on and side-on orientation. To assess a loading force on a target with different impact areas two piezoelectric (PCB) sensors were placed inside a shock tube in parallel and perpendicular orientations to the blast wave. Results show that the face-on pressure is much higher than the static, side-on pressure. In ... |
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| Pharmacokinetic Manipulation and Modeling of the Trigger for JP-8-Induced Skin Irritation |
30-Jan-2009 |
36 pages |
| Authors:
James N McDougal; WRIGHT STATE UNIV DAYTON OH DEPT OF PHARMACOLOGY AND TOXICOLOGYY
|
| Dermal exposure to JP-8 has been shown to cause skin irritation in humans and laboratory animals. We have previously investigated the early responses of mammalian skin to liquid JP-8 contact. We have developed a novel in vivo rat model for the investigation of skin irritation, which maintains the interactions and crosstalk of the wide variety of cells in the epidermis and dermis. We have used this model to investigate early ... |
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| Promethazine as a Novel Prophylaxis and Treatment for Nerve Agent Poisoning |
Dec-2008 |
9 pages |
| Authors:
R K Kan; C P Tompkins; D M Kniffin; T A Hamilton; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD COMPARATIVE PATHOLOGY BRANCH
|
| The present study evaluated promethazine, an FDA-approved antihistamine, for treating the toxic effects of soman (GD). Male Sprague-Dawley rats, weighing 240-300 g, were pretreated 30 minutes prior to or treated less than or equal 1 minute after GD administration (180 mg/kg, sc) with promethazine alone (40 mg/kg, ip) or in combination with oxime reactivator HI-6 (125 mg/kg, ip) and atropine methylnitrate (AMN; 2.0 mg/kg, im). The incidence of convulsions, percentage ... |
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| Prostate Cancer Evaluation: Design, Synthesis and Evaluation of Novel Enzyme-Activated Proton MRI Contrast Agents |
Oct-2008 |
22 pages |
| Authors:
Jian-Xin Yu; TEXAS UNIV SOUTHWESTERN MEDICAL SCHOOL AT DALLAS
|
| The lacZ gene encoding E. coli beta-gal has already been recognized as the most commonly used reporter system in cancer gene therapy. Moreover, prostate-specific membrane antigen (PSMA) has been identified as an ideal antigenic target in prostate cancer. We propose to develop a novel class of Gd(III)-based MRI contrast agents for in vivo detection of beta-gal or PSMA activity. This new concept of the Gd(III)-based MRI contrast agents is composed ... |
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| Translating the Hibernation Phenotype to Human Trauma Care |
24-Sep-2008 |
10 pages |
| Authors:
Sandra L Martin; Hannah V Carey; WISCONSIN UNIV-MADISON
|
| Mammalian hibernators display two unique characteristics that can be exploited for major advancements in surviving blood loss: (1) metabolism is carefully manipulated to achieve controlled reductions in oxygen demand of tissues for energy conservation, and the effect is fully reversible; and (2) hibernators tolerate massive changes in cardiac function, ventilation, tissue perfusion/ reperfusion, and intermediary metabolism that have similarities to shock and other trauma states, yet they are fully protected. ... |
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| Mechanisms Underlying the Breast Cancer Susceptibility Locus Mcs5a |
Jul-2008 |
13 pages |
| Authors:
Bart M Smits; WISCONSIN UNIV-MADISON
|
| For low-penetrance breast cancer risk alleles it is currently unknown how they lead to predisposition. Here, we study the Mcs5a locus that is associated with breast cancer risk in rats and humans. In our rat model we show that the presence of the resistant genotype of two components of the locus (Mcs5a1, Mcs5a2) down regulates the expression of the Fbxo10 gene in the T cells and that this reduced expression ... |
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| Rapid Altitude Acclimatization |
09-May-2008 |
11 pages |
| Authors:
Martha Tissotvanpatot; David Irwin; Robert Gotshall; Karyn Hamilton; COLORADO UNIV HEALTH SCIENCES CENTER AURORA CO
|
| The goal of this seedling was to determine whether cell-free hemoglobin (HBOC) solutions could enhance oxygen carrying capability of blood during exposure to high altitude (14,000 ft and above). The outcome of interest was increased altitude exercise performance secondary to improved oxygen carrying capacity of blood. Male Sprague Dawley rats were habituated to treadmill running, then evaluated on time to fatigue at base altitude (1500 m) and then again at ... |
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| Notch Signaling and Schwann Cell Transformation: Development of a Model System and Application to Human MPNSTs |
MAR 2008 |
|
| Authors:
Tom Kadesch; PENNSYLVANIA UNIV PHILADELPHIA
|
 | This is an annual report that presents data obtained during the grant's third year of funding. The grant addresses the potential role of Notch signaling in the malignant transformation of neurofibromas to MPNSTs in patients with NF1. Our previous work has shown that constitutive expression of Notch can transform rat Schwann cells and that at least on MPNST-derived human Schwann cell line (of three examined) signals via Notch. This report ... |
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| In vitro Toxicity and Inflammatory Response Induced by Copper Nanoparticles in Rat Alveolar Macrophages |
MAR 2008 |
100 pages |
| Authors:
Brian M. Clarke; AIR FORCE INST OF TECH WRIGHT-PATTERSON AFB OH GRADUATE SCHOOL OF ENGINEERING AND MANAGEMENT
|
| Nanotechnology is a thriving industry and has the potential to benefit society in numerous ways. However, not all environmental and human health concerns of nanomaterials have been addressed. Thus, the purpose of this research was to investigate the toxicity and inflammation potential (using cytokines TNF-alpha and IL-6 as indicators) of various sized copper nanoparticles (40, 60, and 80 nm) in rat alveolar macrophages. Toxicity measurements were accomplished by means of ... |
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| Improving Warfighters' Sustainment and Performance in Extreme Environmental Conditions |
18-Feb-2008 |
|
| Authors:
Kevin Kregel; Zhongjie Xun; Ibolja Cernak; Joseph LaManna; JOHNS HOPKINS UNIV LAUREL MD APPLIED PHYSICS LAB
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| In this project, we have developed and verified experimental rat models capable of reproducing physiological responses to extreme environmental conditions, such as simulated high-altitude hypoxia, acute heat stress, and chronic cold stress, comparable to conditions in military relevant scenarios. The major goal of the project was to experimentally test a drug treatment using a heat-shock protein co-inducer (Arimoclomol ; CytRx, Los Angeles, CA) in these rat models of extreme environmental ... |
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| An Unbiased Quantitative Method for Assessing Alterations in Microtubule-Associated Protein 2 (MAP-2) Immunostaining |
Feb-2008 |
34 pages |
| Authors:
Tracey A Hamilton; Robert K Kan; Christina P Tompkins; Denise M Kniffin; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| The present study evaluated the use of computer-assisted image analysis for investigating the temporal alterations in microtubule-associated protein 2 (MAP-2) immunoreactivity in the piriform cortex following acute soman intoxication. Brain samples harvested at various time points after the onset of soman-induced seizures were immunostained with MAP-2 antibody. Color digital images captured with a color digital camera were converted to grayscale images and enhanced to identify the areas of MAP-2 immunoreactivity ... |
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| Development of Hemostatic Agents |
31-Jan-2008 |
24 pages |
| Authors:
Moore; Bob M II; TENNESSEE UNIV CENTER FOR THE HEALTH SCIENCES MEMPHIS
|
| To translate investigational hemostatic agents developed in the rat model to swine models of lethal groin injury and liver laceration. This objective evaluated the efficacy of patch and granule formulations of capsaicin (CP-305) in normal and coagulopathic swine models. The thermal stability of the dmg patches was studied at elevated temperatures to assess shelf life of the hemostatic agent. The remaining objectives were to study the mechanism of action of ... |
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| Interaction Between Dietary Factors and Inflammation in Prostate Carcinogenesis |
DEC 2007 |
25 pages |
| Authors:
Angelo M. De Marzo; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
|
| We are investigating whether inflammation can enhance prostate carcinogenesis in a rat model of dietary charred meat carcinogen induced cancers, and, whether antioxidant and other chemopreventative compounds can reduce prostate cancer in this model. In this period we have extended our rat studies to show that PhIP will cause prostatic intraepithelial neoplasia in the mouse, providing a greatly enhanced ability to study molecular mechanisms of PhIP induced prostate carcinogenesis and ... |
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| Improving Performance Efficiency in the Warfighter |
DEC 2007 |
27 pages |
| Authors:
T. J. Wu; JACKSON (HENRY M) FOUNDATION ROCKVILLE MD
|
| The goal of this project is to design novel compounds that selectively bind estrogen receptor beta (ER(3) to alleviate fear and anxiety-related behaviors and enhance cognitive function ER(3 is a recently described member of the steroid/thyroid hormone receptor superfamily Although it was originally cloned and named based on homology to the classic estrogen receptor (a) ER(3 does not appear to be a critical component of reproductive physiology For example ER(3-knockout-mice ... |
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| TSC2 Happloinsufficiency Leads to a Mutator Phenotype |
01-Nov-2007 |
8 pages |
| Authors:
Cheryl Walker; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Tuberous Sclerosis Complex (TSC) patients develop tumors of the brain, kidney, skin and heart upon loss of either the TSC1 or TSC2 gene, and we are interested in elucidating early molecular events that contribute to loss of TSC2 and in understanding how TSC2 heterozygosity might contribute to this process. Our lab uses the Eker rat, which possesses an inactivating retroviral insertion in one Tsc2 allele (Tsc2Ek/+), as a model to ... |
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| Nitric Oxide Generating Polymeric Coatings for Subcutaneous Glucose Sensors |
OCT 2007 |
11 pages |
| Authors:
Mark E. Meyerhoff; MICHIGAN UNIV ANN ARBOR
|
| Heretofore efforts to develop implantable sensors for real-time clinical monitoring of glucose subcutaneously (SQ) in diabetic patients have been hindered by the unreliable analytical results owing largely to biocompatibility problems induced by sensor implantation (e.g. inflammatory/foreign body response). The goal of this research program is to explore and optimize the chemistries required to fabricate implantable amperometric glucose sensors with outer polymeric coatings that slowly generate low levels of nitric oxide ... |
|
| Prostate Cancer Evaluation: Design, Synthesis, and Evaluation of Novel Enzyme-Activated Proton MRI Contrast Agents |
OCT 2007 |
22 pages |
| Authors:
Jian-Xin Yu; TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER
|
| The lacZ gene encoding E. coli beta-gal has already been recognized as the most commonly used reporter system in cancer gene therapy. Moreover, prostrate-specific membrane antigen (PSMA) has been identified as an ideal antigenic target in prostate cancer. We propose to develop a novel class of Gd(III)-based MRI contrast agents for in vivo detection of beta-gal or PSMA activity. This new concept of the GD(III)-based MRI contrast agents is composed ... |
|
| A Rat Model of Sytemic Chemotherapy for Breast Cancer to Evaluate and Treat Chemobrain |
SEP 2007 |
43 pages |
| Authors:
Kevin C. Little; AUCKLAND UNIV (NEW ZEALAND)
|
| The primary objective of this project was to develop an animal model to measure possible cognitive deficits resulting from chemotherapy. We have established a rat model of multidose human-equivalent combination chemotherapy using cyclophosphamide methotrexate and 5-fluorouracil (CMF) that recapitulates the physical symptoms of chemotherapy treatment. We investigated the effects of this regimen on learning and memory as well as on the production and survival of new neurons in the hippocampus ... |
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| Role of Myelofibrosis in Hematotoxicity of Munitions RDX Environmental Degradation Product MNX |
SEP 2007 |
9 pages |
| Authors:
Sharon A. Meyer; LOUISIANA UNIV AT MONROE
|
| The purpose of this research is to determine mechanisms through which hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), environmental degradation product of high energetic munition hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), causes persistent anemia in the rat. We have hypothesized MNX targets hematopoeitic stem cells and, like other myelosuppressive chemicals, will be fibrogenic to the bone marrow. Findings of this period are: 1) the inability of RDX and MNX to directly oxidize hemoglobin ferrous iron to methemoglobin in vitro ... |
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| Randomized Trial of Neuroprotective Effects of Erythropoietin in Patients Receiving Adjuvant Chemotherapy for Breast Cancer: Positron Emission Tomography and Neuropsychological Study. Addendum |
SEP 2007 |
8 pages |
| Authors:
James Abraham; Gregory Konat; Alicia Krasowska; WEST VIRGINIA UNIV MORGANTOWN
|
| Animal Research Study Amendment An amendment to the study was initiated in April 2005 to include animal experiments. As per published literature, proinflammatory cytokines play a role in the pathogenesis of cognitive dysfunction. The experiments were designed to assess the cytokines before and after chemotherapy in a rat model. We have established an experimental animal model to study chemotherapy-induced cognitive dysfunction observed in the clinical setting. In this model administration ... |
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| Effects of Repeated Sublethal VX Exposure on Operant Time Estimation in Rats |
Aug-2007 |
25 pages |
| Authors:
David W Kahler; Lucille A Lumley; Todd M Myers; John C LaMont; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| Thirty-two rats were trained to stability under a differential-reinforcement-of-low rates 20-s schedule with a sucrose pellet as the reinforcer and a lever press as the operant response. The exposure groups were saline, 0.3, 0.4, and 0.5LD50 VX delivered subcutaneously. Injections were given for three consecutive days and neurobehavioral evaluations were conducted throughout the week of exposure and for two weeks following. Toxic signs scores were significantly higher in the 0.4 ... |
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| The Impact of Exercise on the Vulnerability of Dopamine Neurons to Cell Death in Animal Models of Parkinson's Disease |
01 JUL 2007 |
12 pages |
| Authors:
Michael J. Zpgmond; Amanda Smith; Anthony Liou; PITTSBURGH UNIV PA
|
| Parkinson's disease results in part from the loss of dopamine neurons. We hypothesize that exercise reduces the vulnerability of dopamine neurons to neurotoxin exposure, which is modulated by stress. We have outlined experiments to test this hypothesis in rats treated with one of several neurotoxins, beginning with 6-hydroxydopamine. Over the past year, we increased the size and training of our research team and made a number of observations of direct ... |
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| Breast Cancer and Early Onset Childhood Obesity: Cell Specific Gene Expression in Mammary Epithelia and Adipocytes |
JUL 2007 |
27 pages |
| Authors:
Ignacio G. Camarillo; Maxine Nichols; PURDUE UNIV LAFAYETTE IN
|
| Obesity has become a major health problem in children and adults and is associated with increased breast cancer incidence and mortality The epidemic of childhood obesity is recent and little information exists regarding its association with mammary tumongenesis Towards better understanding this relationship we have developed and characterized a new rat model of childhood onset Diet Induced Obesity (DIO) and breast cancer We have shown that young female rats fed ... |
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| Proteomic Analysis of Genistein Mammary Cancer Chemoprevention |
JUL 2007 |
25 pages |
| Authors:
Coral A. Lamartiniere; ALABAMA UNIV IN BIRMINGHAM
|
| We have developed reproducible methodology for separation biochemical and statistical analysis and identification of mammary gland proteins. We have discovered that GTP-CHl expression is significantly increased shortly following exposure at day 21 by genistein. At day 50 there was significant up-regulation of tyrosine hydroxylase and VEGF-R2. This and previous work suggests that early postnatal (prepubertal) exposure to genistein enhances cell proliferation and cell differentiation and gland maturation. This unique developmental ... |
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| Monoclonal Antibodies to Prevent Use of Mycotoxins as Biological Weapons |
JUL 2007 |
7 pages |
| Authors:
Marta Feldmesser; ALBERT EINSTEIN SCHOOL OF MEDICINE BRONX NY
|
| Aflatoxin exposure causes a broad range of adverse effects including acute hepatic failure hepatic carcinoma and immunosuppression. The ability to weaponize aflatoxins has already been demonstrated raising concern that these potent agents might be used for biowarfare or agroterrorism. Passive antibody therapy is used for the treatment of toxin exposures and its potential for use in the event of bioterrorism has been highlighted. Monoclonal antibodies have been made to afiatoxins ... |
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| Neurobehavioral Effects of Sodium Tungstate Exposure on Rats and Their Progeny |
30 JUN 2007 |
25 pages |
| Authors:
S. M. Mclnturf; M. Y. Bekkedal; A. Olabisi; D. Arfsten; E. Wilfong; R. Casavant; W. Jederberg; P. G. Gunasekar; G. CHAPMAN; NAVAL HEALTH RESEARCH CENTER (DET) WRIGHT-PATTERSON AFB OH ENVIRONMENTAL HEALTH EFFECTS LAB
|
| In the mid 1990's, the use of tungsten as a replacement for lead and depleted uranium began for the manufacture of small arms munitions and armor penetrator munitions, respectively. Recent reports have demonstrated that tungsten can solubilize in soil and is present in some US drinking water supplies, however, little research has been conducted to determine the human health consequences of exposure. The purpose of this study was to use ... |
|
| Identifying Molecular Targets for Chemoprevention in a Rat Model |
01 JUN 2007 |
15 pages |
| Authors:
Ralph W. deVere White; CALIFORNIA UNIV DAVIS
|
| The purpose of this grant is to determine the molecular events that occur in the dorsal and ventral lobes of the rat prostate gland after 20 weeks of exposure to PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine). PhIP is a potent inducer of mutations in the rate prostate where we have previously shown that it forms bulky DNA adducts. The scope of this research includes: 1)Generation of a rat model, 2) Analysis of the rat ... |
|
| Characterizing a Rat Brca2 Knockout Model |
01 MAY 2007 |
51 pages |
| Authors:
Michael N. Gould; WISCONSIN UNIV-MADISON
|
| Brca2 mutation carriers, while rare in the population have a high probability to develop breast cancer. In order to better understand the etiology of this disease as well as to develop prevention and treatment strategies for it we require good animal models. In this project we characterized the first rat knockout prnduced which was that of the Brca2 locus. We showed that Brca24-rats survive and develop multiple cancers but not ... |
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| Identifying ECM Mediators of Tumor Cell Dormancy |
MAY 2007 |
14 pages |
| Authors:
Pepper Schedin; COLORADO UNIV HEALTH SCIENCES CENTER AURORA CO
|
| Characterize the compositional and functional changes in mammary stroma that result from tamoxifen treatment. Approach: R75 mature female Sprague Dawley rats were randomized into three groups of 25 each; Gp1 nulliparous control, and Gp 2 tamoxifen treated (0.5 mg/tamoxifen body weight, s.c. injection for 30 days)and Gp 3 tamoxifen treated (1.0 mg tamoxifen dose). ECM was harvested from the mammary glands of Gps 1 biochemical and functional characterizations. The ECM ... |
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| In Utero Exposure to Cadmium, Mammary Gland Development, and Breast Cancer Risk |
MAY 2007 |
22 pages |
| Authors:
Jennifer D. Webster; GEORGETOWN UNIV WASHINGTON DC
|
| In utero exposures to estrogen or estrogen mimics such may alter later breast cancer risk. Some of these estrogen-responsive pathways utilized during fetal development, are re-employed at times of tissue remodeling or wound healing during adulthood. These signal transduction systems effect proliferation, differentiation and apoptosis which in turn may affect later breast cancer risk. The heavy metal cadmium potently binds to and activates the estrogen receptor, having a half life ... |
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| Ethanol and Mesolimbic Serotonin/Dopamine Interactions via 5HT-1B Receptors |
MAR 2007 |
99 pages |
| Authors:
Quingshan Yan; ILLINOIS UNIV AT CHICAGO
|
| The purpose was to investigate whether activation of 5-HT1B receptors within the ventral tegmental area (VTA) facilitated dopamine (DA) transmission in the ipsilateral nucleus accumbens (NACC) and potentiated ethanol-induced increases in NACC DA by 5- HT1B receptor-mediated GABA mechanisms. The data derived from microdialysis studies performed in rats and 5-HT1B receptor knockout mice, and those obtained from superfusion experiments consistently showed that activation of VTA 5-HT1B receptors facilitated mesolimbic DA ... |
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| Non-Invasive Monitoring for Optimization of Therapeutic Drug Delivery by Biodegradable Fiber to Prostate Tumor |
FEB 2007 |
30 pages |
| Authors:
Dan Popa; Hanli Liu; Liping Tang; TEXAS UNIV AT ARLINGTON
|
| Chemotherapeutic drugs delivered by systematic administration exhibit great toxicity; patients have to endure suffering from frequent injection or low dose IV treatment. Thus controlled release and of these drugs and real-time monitoring of the effects of the drug can be an better treatment modality. The Hypotheses are (1): A near-infrared (NIR) imager can non-invasively monitor the vascular oxygenation and blood volumes in prostate tumors. (2): The dynamic response of prostate ... |
|
| Characterization of Maze Performance in Adrenalectomized Sleep Disrupted Rats: A Comparison of Radial Arm Maze Performance between Adrenalectomized and Sham Adrenalectomized Sleep Disrupted Rats |
JAN 2007 |
36 pages |
| Authors:
Laura Mery; TEXAS UNIV AT SAN ANTONIO
|
| Sleep disruption affects performance in rats in several behavioral paradigms. Elevation of plasma corticosterine is associated with stress, and with sleep disruption in rats. Elevated corticosterone may contribute to dendritic regression in the hippocampus, a brain region associated with spatial learning. The working hypothesis of this study was removing adrenal glands in a rat will ameliorate the effects of sleep disruption on maze performance. Animals adrenalectomized and sham adrenalectomized were ... |
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| Autologous Marrow-Derived Stem Cell-Seeded Gene-Supplemented Collagen Scaffolds for Spinal Cord Regeneration as a Treatment for Paralysis |
JAN 2007 |
29 pages |
| Authors:
Myron Spector; BOSTON VA RESEARCH INST MA
|
| The long-term objective of this research is to develop a device for treating spinal cord injury. The specific aims of the proposed study are to test new types of collagen tubes and porous collagen scaffolds. Moreover we will be investigating the effects of incorporating genes from nerve growth factors into the collagen scaffolds and seeding the scaffolds with marrow-derived mesenchymal stem cells. The standardized defect site is a 5-mm gap ... |
|
| TSC2 Happloinsufficiency Leads to a Mutator Phenotype |
NOV 2006 |
8 pages |
| Authors:
John D. Short; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Tuberous Sclerosis Complex (TSC) patients develop tumors of the brain, kidney, skin and heart upon loss of either the TSC1 or TSC2 gene, and we are interested in elucidating early molecular events that contribute to loss of TSC2 and in understanding how TSC2 heterozygosity might contribute to this process. Our lab uses the Eker rat, which possesses an inactivating retroviral insertion in one Tsc2 allele (Tsc2Ek/+), as a model to ... |
|
| Tc-99m Labeled and VIP-Receptor Targeted Liposomes for Effective Imaging of Breast Cancer |
01 SEP 2006 |
88 pages |
| Authors:
Hayat Onyuksel; ILLINOIS UNIV AT CHICAGO
|
| However, current methods of breast cancer detection cannot provide accurate results. This study was conceived to begin to address this issue by developing and testing a novel method of active targeting of radionuclide (Tc-99m) encapsulating sterically stabilized liposomes (SSL) for gamma scintigraphic imaging of breast cancer. This non-invasive imaging modality utilizes both overexpression of vasoactive intestinal peptide (VIP) receptors in breast tumor and distinct biology of the tumors (leaky vasculature) ... |
|
| The Mustard Consortium's Elucidation of the Pathophysiology of Sulfur Mustard and Antidote Development |
SEP 2006 |
36 pages |
| Authors:
Peter A. Ward; Milton G. Smith; Keith Crawford; William Stone; Salil Das; Alfred Sciuto; Dana Anderson; MICHIGAN UNIV ANN ARBOR
|
| The Mustards Consortium has utilized both in vivo and in vitro models simultaneously to continue to elucidate mustard gas pathophysiology. In previous work done by the MC it was found that CEES, the mustard analogue, induced oxidative stress and was its primary mechanism of action. Consequently, NAC (N-acetyl cystiene) was found to be protective as a prophylaxis and treatment. A combination of a water and fat soluble antioxidant encapsulated in ... |
|
| New Imaging Kit for Assessment of Estrogen Receptors with Single Photon Emission Computed Tomography |
SEP 2006 |
91 pages |
| Authors:
E. E. Kim; David J. Yang; Ali Azhdarinia; M D ANDERSON CANCER CENTER HOUSTON TX
|
| To evaluate the feasibility of using 99mTc-glutamate peptide-estradiol (GAP-EDL) in imaging estrogen receptor positive (ER +) diseases. Methods: 3-Aminoethyl estradiol (EDL) was conjugated glutamate peptide (GAP) to yield GAP-EDL. Cellular uptake studies of 99mTc-GAP-EDL were conducted in ER (+) cell lines (MCF7 13762 and T47D). To demonstrate whether GAP-EDL increases MAP kinase acbvafion Western blot analysis of GAP-EDL was performed in 13762 cells. Biodistribution was conducted in 13762 breast tumor-bearing ... |
|
| Role of Myelofibrosis in Hematotoxicity of Munition RDX Environmental Degradation Product MNX |
SEP 2006 |
10 pages |
| Authors:
Sharon A. Meyer; LOUISIANA UNIV AT MONROE
|
| The purpose of this research is to determine mechanisms through which hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), environmental degradation product of high energetic munition hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), causes persistent anemia in the rat. We have hypothesized MNX targets hematopoeitic stem cells and, like other myelosuppressive chemicals, will be fibrogenic to the bone marrow. Findings of this period are: 1) additional MNX suppressive effects on peripheral blood cells of myeloid lineage and similar effects of RDX ... |
|
| Mechanism for Prenatal LPS-Induced DA Neuron Loss |
SEP 2006 |
142 pages |
| Authors:
Paul M. Carvey; RUSH UNIV MEDICAL CENTER CHICAGO IL
|
| In nonfamilial Parkinson's Disease (PD) the etiologies of the majority of patients are still unknown. However, recent advances by the authors suggest that prenatal exposure to the bacterial toxin lipopolysaccharide (LPS) could be an important etiology for some PD patients. A key finding is that animals exposed to LPS prenatally display fewer than the normal number of dopamine (DA) neurons in the midbrain, the hallmark of PD pathology in human ... |
|
| Amygdala, Anxiety and Alpha(1) Adrenoceptors: Investigations Utilizing a Rodent Model of Traumatic Stress |
23 AUG 2006 |
95 pages |
| Authors:
Sean T. Manion; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD DEPT OF NEUROLOGY
|
| Exposure to traumatic stress can result in post-traumatic stress disorder (PTSD), characterized by indicators including exaggerated acoustic startle response (ASR) and alterations in processing of emotional memory. Similar effects can be seen in an animal model of traumatic stress. The basolateral amygdala (BLA) is an area known to be involved in the processing of emotional memory and startle modulation. Synaptic plasticity in the BLA is thought to play a key ... |
|
| Behavioral and Biological Effects of Housing Conditions and Stress in Male Rats - Relevance to Heart Disease |
AUG 2006 |
104 pages |
| Authors:
Sarah T. Shafer; UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD
|
| The present experiment examined the effects of environmental enrichment and stress on behavioral and biological measures relevant to cardiovascular disease risk (i.e. plasma corticosterone levels elevated plus maze locomotor activity in an open field chamber body weight and food consumption and heart morphology). Seventy-two Sprague-Dawley rats were raised in enriched environments (social or social and physical enrichment) or non-enriched environments for a total of 48 days. Half of the animals ... |
|
| Characterization of Genetic Modifiers of Estrogen-Induced Mammary Cancer |
JUL 2006 |
10 pages |
| Authors:
Beverly Schaffer; NEBRASKA UNIV MEDICAL CENTER OMAHA
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| Prolonged exposure to estrogens is considered a major risk factor for development of breast cancer. When treated with the naturally occurring estrogen, 17 -estradiol, ACI rats develop mammary cancers in over 90% of the population at risk. Genetic crosses between the susceptible ACI rat and resistant Copenhagen (COP) or Brown Norway (BN) rats identified a region on chromosome 5 (Emca1) that modified the development of estrogen-induced mammary cancer. The purpose ... |
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| Integrated Cancer Research in Five Thematic Areas of Interest |
JUL 2006 |
10 pages |
| Authors:
Wadie F. Bahou; STATE UNIV OF NEW YORK AT STONY BROOK
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| During the last FY of the award, the Cancer Institute of Long Island benefited from CDMRP funding in a manner consistent with the proposed activities of the award. In the area of core instrumentation acquisition, an Olympus upright microscope has been added and integrated in to the previously funded two-photon system. The new instrument is essential for in vivo imaging for mice and rats. The previously funded Zeiss TIRF Microscope ... |
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| The Impact of Exercise on the Vulnerability of Dopamine Neurons to Cell Death in Animal Models of Parkinson's Disease |
JUL 2006 |
10 pages |
| Authors:
Michael J. Zigmond; Amanda Smith; Anthony Liou; PITTSBURGH UNIV PA
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| Parkinson's disease results in part from the loss of dopamine neurons. We hypothesize that exercise reduces the vulnerability of dopamine neurons to neurotoxin exposure, whereas stress increases vulnerability. We have outlined experiments to test this hypothesis in rats treated with one of several neurotoxins, beginning with 6-hydroxydopamine. Over the past year, we increased the size and training of our research team and made a number of observations of direct relevance ... |
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| Development of a Protocol to Evaluate Neuronal Injury and Loss Following Soman-Induced Seizures Using NeuN and Fluoro-Jade C |
Jul-2006 |
16 pages |
| Authors:
Tracey A Hamilton; Robert K Kan; Denise M Fath; Christina P Tompkins; Erik A Johnson; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| Previously, we examined regional neuronal damage following soman-induced seizures using Fluoro-Jade (FJ), which exhibits a marked affinity for degenerating neurons. However, with FJ alone, the degree of neuronal loss cannot be ascertained. The present study was conducted to develop a protocol to double-label a single paraffin-embedded rat brain section with both Fluoro-Jade C (FJ-C) and Neuronspecific nuclear protein (NeuN) to evaluate neuronal injury. Rats pretreated with HI-6 (125 mg/kg, i.p.) ... |
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