8 results on '"Perkins, Michael W."'
Search Results
2. Development of a Model for Nerve Agent Inhalation in Conscious Rats
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ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Wong, Benjamin, Perkins, Michael W, Santos, Mariton D, Rodriguez, Ashley M, Murphy, Gleeson, Sciuto, Alfred M, ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Wong, Benjamin, Perkins, Michael W, Santos, Mariton D, Rodriguez, Ashley M, Murphy, Gleeson, and Sciuto, Alfred M
- Abstract
This study characterizes the development of a head-out inhalation exposure system for assessing respiratory toxicity of vaporized chemical agents in untreated, non-anesthetized rats. The organophosphate diisopropyl fluorophosphate (DFP) induces classical cholinergic toxicity following inhalation exposure and was utilized to validate the effectiveness of this newly designed inhalation exposure system. A saturator cell apparatus was used to generate DFP vapor at 9750, 10950, 12200, 14625 and 19500mg min/m(expn 3) which was carried by filtered nitrogen into a glass mixing tube, where it combined with ambient air before being introduced to the custom-made glass exposure chamber. Male Sprague-Dawley rats (250 300 g) were restrained in individual head-out plethysmography chambers, which acquired respiratory parameters before, during and after agent exposure. All animals were acclimated to the exposure system prior to exposure to reduce novel environment-induced stress. The LCt50, as determined by probit analysis, was 12 014mg min/m3. Weight loss in exposed animals was dose-dependent and ranged from 8 to 28% of their body weight 24 h after exposure. Increased salivation, lacrimation, urination, defecation (SLUD) and mild muscular fasciculation were observed in all DFP-exposed animals during and immediately following exposure. In all exposed animals, DFP vapor produced significant inhibition of acetylcholinesterase (AChE) activity in cardiac blood, bronchoalveolar lavage fluid (BALF), whole brain and lung tissue as well as alterations in tidal volume and minute volume. These studies have provided valuable information leading to the initiation of studies evaluating inhalational toxicity and treatments following exposure to the more lethal and potent chemical warfare nerve agents., The original document contains color images. Published in Toxicology Mechanisms and Methods, v23 n7 p537-547, 2013.
- Published
- 2013
3. Inhalation toxicity of soman vapor in non-anesthetized rats: A preliminary assessment of inhaled bronchodilator or steroid therapy
- Author
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Perkins, Michael W., primary, Wong, Benjamin, additional, Rodriguez, Ashley, additional, Devorak, Jennifer L., additional, Alves, Derron A., additional, Murphy, Gleeson, additional, and Sciuto, Alfred M., additional
- Published
- 2013
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4. Amelioration of Radiation-Induced Hematopoietic and Gastrointestinal Damage by Ex-RAD (trademark) in Mice
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UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD, Ghosh, Sanchita P, Kulkarni, Shilpa, Perkins, Michael W, Hieber, Kevin, Pessu, Roli L, Gambles, Kristen, Maniar, Manoj, Kao, Tzu-Cheg, Seed, Thomas M, Kumar, K S, UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD, Ghosh, Sanchita P, Kulkarni, Shilpa, Perkins, Michael W, Hieber, Kevin, Pessu, Roli L, Gambles, Kristen, Maniar, Manoj, Kao, Tzu-Cheg, Seed, Thomas M, and Kumar, K S
- Abstract
The aim of the present study was to assess recovery from hematopoietic and gastrointestinal damage by Ex-RAD , also known as ON01210.Na (4-carboxystyryl-4-chlorobenzylsulfone, sodium salt), after total body radiation. In our previous study, we reported that Ex-RAD, a small-molecule radioprotectant, enhances survival of mice exposed to gamma radiation, and prevents radiation-induced apoptosis as measured by the inhibition of radiation-induced protein 53 (p53) expression in cultured cells. We have expanded this study to determine best effective dose, dose-reduction factor (DRF), hematological and gastrointestinal protection, and in vivo inhibition of p53 signaling. A total of 500 mg/kg of Ex-RAD administered at 24 h and 15 min before radiation resulted in a DRF of 1.16. Ex-RAD ameliorated radiation-induced hematopoietic damage as monitored by the accelerated recovery of peripheral blood cells, and protection of granulocyte macrophage colony-forming units (GM-CFU) in bone marrow. Western blot analysis on spleen indicated that Ex- RAD treatment inhibited p53 phosphorylation. Ex-RAD treatment reduces terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay (TUNEL)-positive cells in jejunum compared with vehicletreated mice after radiation injury. Finally, Ex-RAD preserved intestinal crypt cells compared with the vehicle control at 13 and 14 Gy. The results demonstrated that Ex-RAD ameliorates radiation-induced peripheral blood cell depletion, promotes bone marrow recovery, reduces p53 signaling in spleen and protects intestine from radiation injury., Pub. in Journal of Radiation research, p1-11, 2012. Sponsored in part by ARMY MEDICAL RESEARCH AND MATERIEL COMMAND.
- Published
- 2012
5. THE ROLE OF PROTEIN KINASE C IN LIPOPOLYSACCHARIDE-INDUCED MYOCARDIAL DEPRESSION IN GUINEA PIGS
- Author
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Heard, Stephen O., primary, Toth, Ildiko E., additional, Perkins, Michael W., additional, and Leonard, Jack L., additional
- Published
- 1994
- Full Text
- View/download PDF
6. Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD® in mice
- Author
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Ghosh, Sanchita P., Kulkarni, Shilpa, Perkins, Michael W., Hieber, Kevin, Pessu, Roli L., Gambles, Kristen, Maniar, Manoj, Kao, Tzu-Cheg, Seed, Thomas M., and Kumar, K. Sree
- Abstract
The aim of the present study was to assess recovery from hematopoietic and gastrointestinal damage by Ex-RAD®, also known as ON01210.Na (4-carboxystyryl-4-chlorobenzylsulfone, sodium salt), after total body radiation. In our previous study, we reported that Ex-RAD, a small-molecule radioprotectant, enhances survival of mice exposed to gamma radiation, and prevents radiation-induced apoptosis as measured by the inhibition of radiation-induced protein 53 (p53) expression in cultured cells. We have expanded this study to determine best effective dose, dose-reduction factor (DRF), hematological and gastrointestinal protection, and in vivo inhibition of p53 signaling. A total of 500 mg/kg of Ex-RAD administered at 24 h and 15 min before radiation resulted in a DRF of 1.16. Ex-RAD ameliorated radiation-induced hematopoietic damage as monitored by the accelerated recovery of peripheral blood cells, and protection of granulocyte macrophage colony-forming units (GM-CFU) in bone marrow. Western blot analysis on spleen indicated that Ex-RAD treatment inhibited p53 phosphorylation. Ex-RAD treatment reduces terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay (TUNEL)-positive cells in jejunum compared with vehicle-treated mice after radiation injury. Finally, Ex-RAD preserved intestinal crypt cells compared with the vehicle control at 13 and 14 Gy. The results demonstrated that Ex-RAD ameliorates radiation-induced peripheral blood cell depletion, promotes bone marrow recovery, reduces p53 signaling in spleen and protects intestine from radiation injury.
- Published
- 2012
- Full Text
- View/download PDF
7. THE ROLE OF PROTEIN KINASE C IN LIPOPOLYSACCHARIDEINDUCED MYOCARDIAL DEPRESSION IN GUINEA PIGS
- Author
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Heard, Stephen O., Toth, Ildiko E., Perkins, Michael W., and Leonard, Jack L.
- Abstract
The effect of lipopolysaccharide (LPS) on cardiac protein kinase C (PKC) activation and cardiac depression was evaluated. Guinea pigs (n = 44) received intraperitoneal injections of saline or Escherichia coli LPS (2 mg/kg). Left atria were harvested 16 h later and suspended in oxygenated low calcium (1 mM) (n = 24) or high calcium (5 mM) (n = 20) 30°C Krebs-Henseleit buffer. Atria were treated with H-7 (n = 23), a PKC inhibitor, or vehicle (n = 21). Contractile responses to changes in preload and stimulating frequency, in the resting and potentiated states, and to escalating doses of phenylephrine were measured. PKC activation in ventricular muscle was also determined. LPS activated ventricular PKC (p< .05) but treatment with H-7 failed to reverse LPS-induced atrial dysfunction in the low calcium buffer. Contractile function in the potentiated state indicated that LPS appears to interfere with calcium release from the sarcoplasmic reticulum (SR). The contractile response to phenylephrine was markedly attenuated in atria harvested from endotoxic animals. These data indicate that LPS-induced cardiac depression is mediated, in part, by alterations in SR calcium release. LPS activates cardiac PKC but a causal relationship among LPS, PKC, and cardiac dysfunction remains to be established.
- Published
- 1994
8. Amelioration of radiation-induced hematopoietic and gastrointestinal damage by Ex-RAD(R) in mice.
- Author
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Ghosh SP, Kulkarni S, Perkins MW, Hieber K, Pessu RL, Gambles K, Maniar M, Kao TC, Seed TM, and Kumar KS
- Subjects
- Animals, Dose-Response Relationship, Radiation, Granulocyte-Macrophage Progenitor Cells metabolism, In Situ Nick-End Labeling, Male, Mice, Mice, Inbred C3H, Phosphorylation, Radiation Injuries prevention & control, Spleen metabolism, Time Factors, Gastrointestinal Tract radiation effects, Hematopoietic System radiation effects, Neutropenia drug therapy, Radiation-Protective Agents pharmacology, Sulfonamides pharmacology
- Abstract
The aim of the present study was to assess recovery from hematopoietic and gastrointestinal damage by Ex-RAD(®), also known as ON01210.Na (4-carboxystyryl-4-chlorobenzylsulfone, sodium salt), after total body radiation. In our previous study, we reported that Ex-RAD, a small-molecule radioprotectant, enhances survival of mice exposed to gamma radiation, and prevents radiation-induced apoptosis as measured by the inhibition of radiation-induced protein 53 (p53) expression in cultured cells. We have expanded this study to determine best effective dose, dose-reduction factor (DRF), hematological and gastrointestinal protection, and in vivo inhibition of p53 signaling. A total of 500 mg/kg of Ex-RAD administered at 24 h and 15 min before radiation resulted in a DRF of 1.16. Ex-RAD ameliorated radiation-induced hematopoietic damage as monitored by the accelerated recovery of peripheral blood cells, and protection of granulocyte macrophage colony-forming units (GM-CFU) in bone marrow. Western blot analysis on spleen indicated that Ex-RAD treatment inhibited p53 phosphorylation. Ex-RAD treatment reduces terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay (TUNEL)-positive cells in jejunum compared with vehicle-treated mice after radiation injury. Finally, Ex-RAD preserved intestinal crypt cells compared with the vehicle control at 13 and 14 Gy. The results demonstrated that Ex-RAD ameliorates radiation-induced peripheral blood cell depletion, promotes bone marrow recovery, reduces p53 signaling in spleen and protects intestine from radiation injury.
- Published
- 2012
- Full Text
- View/download PDF
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