Topical application of green and white tea extracts provides protection from solar-simulated ultraviolet light in human skin.

PubMed

Camouse, Melissa M; Domingo, Diana Santo; Swain, Freddie R; Conrad, Edward P; Matsui, Mary S; Maes, Daniel; Declercq, Lieve; Cooper, Kevin D; Stevens, Seth R; Baron, Elma D

2009-06-01

Tea polyphenols have been found to exert beneficial effects on the skin via their antioxidant properties. We sought to determine whether topical application of green tea or white tea extracts would prevent simulated solar radiation-induced oxidative damages to DNA and Langerhans cells that may lead to immune suppression and carcinogenesis. Skin samples were analysed from volunteers or skin explants treated with white tea or green tea after UV irradiation. In another group of patients, the in vivo immune protective effects of green and white tea were evaluated using contact hypersensitivity to dinitrochlorobenzene. Topical application of green and white tea offered protection against detrimental effects of UV on cutaneous immunity. Such protection is not because of direct UV absorption or sunscreen effects as both products showed a sun protection factor of 1. There was no significant difference in the levels of protection afforded by the two agents. Hence, both green tea and white tea are potential photoprotective agents that may be used in conjunction with established methods of sun protection.

Evolution of and perspectives on therapeutic approaches to nerve agent poisoning.

PubMed

Masson, Patrick

2011-09-25

After more than 70 years of considerable efforts, research on medical defense against nerve agents has come to a standstill. Major progress in medical countermeasures was achieved between the 50s and 70s with the development of anticholinergic drugs and carbamate-based pretreatment, the introduction of pyridinium oximes as antidotes, and benzodiazepines in emergency treatments. These drugs ensure good protection of the peripheral nervous system and mitigate the acute effects of exposure to lethal doses of nerve agents. However, pyridostigmine and cholinesterase reactivators currently used in the armed forces do not protect/reactivate central acetylcholinesterases. Moreover, other drugs used are not sufficiently effective in protecting the central nervous system against seizures, irreversible brain damages and long-term sequelae of nerve agent poisoning.New developments of medical counter-measures focus on: (a) detoxification of organophosphorus molecules before they react with acetylcholinesterase and other physiological targets by administration of stoichiometric or catalytic scavengers; (b) protection and reactivation of central acetylcholinesterases, and (c) improvement of neuroprotection following delayed therapy.Future developments will aim at treatment of acute and long-term effects of low level exposure to nerve agents, research on alternative routes for optimizing drug delivery, and therapies. Though gene therapy for in situ generation of bioscavengers, and cell therapy based on neural progenitor engraftment for neuronal regeneration have been successfully explored, more studies are needed before practical medical applications can be made of these new approaches. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

FTIR-ATR evaluation of topical skin protectants useful for sulfur mustard and related compounds

NASA Astrophysics Data System (ADS)

Braue, Ernest H., Jr.; Litchfield, Marty R.; Bangledorf, Catherine R.; Rieder, Robert G.

1992-03-01

The US Army has a need to develop topical protectants that can decrease the effects of cutaneous exposure to chemical warfare (CW) agents. Such materials would enhance a soldier's ability to carry out the mission in a chemically hostile environment, would lessen the burden on medical personnel, and may allow the casualties to return to duty in a shorter period of time than might otherwise be possible. In a preliminary report (E. H. Braue, Jr. and M. G. Pannella, Applied Spectrosc., 44, 1061 (1990)), we described a unique analytical method using FT-IR spectroscopy and the horizontal attenuated total reflectance (ATR) accessory for evaluating the effectiveness of topical skin protectants (TSPs) against penetration by chemical agents. We now describe the application of this method to the chemical warfare agent sulfur mustard (HD).

Neurosteroids for the potential protection of humans against organophosphate toxicity.

PubMed

Reddy, Doodipala Samba

2016-08-01

This article describes the therapeutic potential of neurosteroids as anticonvulsant antidotes for chemical intoxication caused by organophosphate pesticides and nerve agents or gases like sarin and soman. Toxic manifestations following nerve agent exposure, as evident in chemical attacks in Japan and Syria, include hypersecretion, respiratory distress, tremors, convulsions leading to status epilepticus (SE), and death. Benzodiazepines, such as diazepam, are the current anticonvulsants of choice for controlling nerve agent-induced life-threatening seizures, SE, and brain injury. Benzodiazepines can control acute seizures when given early, but they are less effective for delayed treatment of SE, which is characterized by rapid desensitization of synaptic GABA A receptors, benzodiazepine resistance, and brain injury. Neurosteroid-sensitive extrasynaptic GABA A receptors, however, remain unaffected by such events. Thus, anticonvulsant neurosteroids may produce more effective protection than benzodiazepines against a broad spectrum of chemical agents, even when given late after nerve agent exposure. © 2016 New York Academy of Sciences.

A Model for Assessing the Clinical and Economic Benefits of Bone-forming Agents for Reducing Fractures in Postmenopausal Women at High, Near-term Risk of Osteoporotic Fracture.

PubMed

O'Hanlon, Claire E; Parthan, Anju; Kruse, Morgan; Cartier, Shannon; Stollenwerk, Bjorn; Jiang, Yawen; Caloyeras, John P; Crittenden, Daria B; Barron, Richard

2017-07-01

The goal of this study was to assess and compare the potential clinical and economic value of emerging bone-forming agents using the only currently available agent, teriparatide, as a reference case in patients at high, near-term (imminent, 1- to 2-year) risk of osteoporotic fractures, extending to a lifetime horizon with sequenced antiresorptive agents for maintenance treatment. Analyses were performed by using a Markov cohort model accounting for time-specific fracture protection effects of bone-forming agents followed by antiresorptive treatment with denosumab. The alternative bone-forming agent profiles were defined by using assumptions regarding the onset and total magnitude of protection against fractures with teriparatide. The model cohort comprised 70-year-old female patients with T scores below -2.5 and a previous vertebral fracture. Outcomes included clinical fractures, direct costs, and quality-adjusted life years. The simulated treatment strategies were compared by calculating their incremental "value" (net monetary benefit). Improvements in the onset and magnitude of fracture protection (vs the teriparatide reference case) produced a net monetary benefit of $17,000,000 per 10,000 treated patients during the (1.5-year) bone-forming agent treatment period and $80,000,000 over a lifetime horizon that included 3.5 years of maintenance treatment with denosumab. Incorporating time-specific fracture effects in the Markov cohort model allowed for estimation of a range of cost savings, quality-adjusted life years gained, and clinical fractures avoided at different levels of fracture protection onset and magnitude. Results provide a first estimate of the potential "value" new bone-forming agents (romosozumab and abaloparatide) may confer relative to teriparatide. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

40 CFR Appendix L to Subpart G of... - Substitutes Listed in the January 27, 2003, Final Rule, Effective March 28, 2003

Code of Federal Regulations, 2014 CFR

2014-07-01

... environments protected by HFC227-BC extinguishing systemsEach HFC227-BC extinguisher should be clearly labelled... Agent Fire Extinguishing Systems. See additional comments 1, 2, 3, 4, 5. Additional comments. 1—Should... or performance requirements. 4—The agent should be recovered from the fire protection system in...

40 CFR Appendix L to Subpart G of... - Substitutes Listed in the January 27, 2003, Final Rule, Effective March 28, 2003

Code of Federal Regulations, 2013 CFR

2013-07-01

... environments protected by HFC227-BC extinguishing systemsEach HFC227-BC extinguisher should be clearly labelled... Agent Fire Extinguishing Systems. See additional comments 1, 2, 3, 4, 5. Additional comments. 1—Should... or performance requirements. 4—The agent should be recovered from the fire protection system in...

40 CFR Appendix L to Subpart G of... - Substitutes Listed in the January 27, 2003, Final Rule, Effective March 28, 2003

Code of Federal Regulations, 2012 CFR

2012-07-01

... environments protected by HFC227-BC extinguishing systemsEach HFC227-BC extinguisher should be clearly labelled... Agent Fire Extinguishing Systems. See additional comments 1, 2, 3, 4, 5. Additional comments. 1—Should... or performance requirements. 4—The agent should be recovered from the fire protection system in...

Safinamide and flecainide protect axons and reduce microglial activation in models of multiple sclerosis.

PubMed

Morsali, Damineh; Bechtold, David; Lee, Woojin; Chauhdry, Summen; Palchaudhuri, Upayan; Hassoon, Paula; Snell, Daniel M; Malpass, Katy; Piers, Thomas; Pocock, Jennifer; Roach, Arthur; Smith, Kenneth J

2013-04-01

Axonal degeneration is a major cause of permanent disability in the inflammatory demyelinating disease multiple sclerosis, but no therapies are known to be effective in axonal protection. Sodium channel blocking agents can provide effective protection of axons in the white matter in experimental models of multiple sclerosis, but the mechanism of action (directly on axons or indirectly via immune modulation) remains uncertain. Here we have examined the efficacy of two sodium channel blocking agents to protect white matter axons in two forms of experimental autoimmune encephalomyelitis, a common model of multiple sclerosis. Safinamide is currently in phase III development for use in Parkinson's disease based on its inhibition of monoamine oxidase B, but the drug is also a potent state-dependent inhibitor of sodium channels. Safinamide provided significant protection against neurological deficit and axonal degeneration in experimental autoimmune encephalomyelitis, even when administration was delayed until after the onset of neurological deficit. Protection of axons was associated with a significant reduction in the activation of microglia/macrophages within the central nervous system. To clarify which property of safinamide was likely to be involved in the suppression of the innate immune cells, the action of safinamide on microglia/macrophages was compared with that of the classical sodium channel blocking agent, flecainide, which has no recognized monoamine oxidase B activity, and which has previously been shown to protect the white matter in experimental autoimmune encephalomyelitis. Flecainide was also potent in suppressing microglial activation in experimental autoimmune encephalomyelitis. To distinguish whether the suppression of microglia was an indirect consequence of the reduction in axonal damage, or possibly instrumental in the axonal protection, the action of safinamide was examined in separate experiments in vitro. In cultured primary rat microglial cells activated by lipopolysaccharide, safinamide potently suppressed microglial superoxide production and enhanced the production of the anti-oxidant glutathione. The findings show that safinamide is effective in protecting axons from degeneration in experimental autoimmune encephalomyelitis, and that this effect is likely to involve a direct effect on microglia that can result in a less activated phenotype. Together, this work highlights the potential of safinamide as an effective neuroprotective agent in multiple sclerosis, and implicates microglia in the protective mechanism.

A structure-activity analysis of the variation in oxime efficacy against nerve agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maxwell, Donald M.; Koplovitz, Irwin; Worek, Franz

2008-09-01

A structure-activity analysis was used to evaluate the variation in oxime efficacy of 2-PAM, obidoxime, HI-6 and ICD585 against nerve agents. In vivo oxime protection and in vitro oxime reactivation were used as indicators of oxime efficacy against VX, sarin, VR and cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy after sc administration of nerve agent. Analysis of in vitro reactivation was conducted with second-order rate contants (k{sub r2}) for oxime reactivation of agent-inhibited acetylcholinesterase (AChE) from guinea pig erythrocytes. In vivo oxime PR and inmore » vitro k{sub r2} decreased as the volume of the alkylmethylphosphonate moiety of nerve agents increased from VX to cyclosarin. This effect was greater with 2-PAM and obidoxime (> 14-fold decrease in PR) than with HI-6 and ICD585 (< 3.7-fold decrease in PR). The decrease in oxime PR and k{sub r2} as the volume of the agent moiety conjugated to AChE increased was consistent with a steric hindrance mechanism. Linear regression of log (PR-1) against log (k{sub r2} {center_dot} [oxime dose]) produced two offset parallel regression lines that delineated a significant difference between the coupling of oxime reactivation and oxime protection for HI-6 and ICD585 compared to 2-PAM and obidoxime. HI-6 and ICD585 appeared to be 6.8-fold more effective than 2-PAM and obidoxime at coupling oxime reactivation to oxime protection, which suggested that the isonicotinamide group that is common to both of these oximes, but absent from 2-PAM and obidoxime, is important for oxime efficacy.« less

Comparative Efficacy and Acceptability of Anti-Diabetic Agents for Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and Network Meta-analysis.

PubMed

Cao, Bing; Rosenblat, Joshua D; Brietzke, Elisa; Park, Caroline; Lee, Yena; Musial, Natalie; Pan, Zihang; Mansur, Rodrigo B; McIntyre, Roger S

2018-05-23

The current meta-analysis compares the efficacy (i.e., pro-cognitive effects) and acceptability of anti-diabetic agents for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Cochrane Library (CENTRAL), PubMed/MEDLINE, EMBASE and PsycINFO were searched from inception to January 15, 2018 for randomized controlled trials (RCTs) comparing anti-diabetic agents with placebo and/or another active anti-diabetic agent for the treatment of AD or MCI. Nineteen eligible studies (n = 4,855) evaluating the effects of six different anti-diabetic drugs (i.e., intranasal insulin, pioglitazone, rosiglitazone, metformin, sitagliptin and liraglutide) were included. The results of 29 pairwise comparisons indicated that cognition was significantly improved in subjects treated with anti-diabetic agents compared to placebo. Pioglitazone 15-30 mg demonstrated the greatest efficacy compared to placebo in network meta-analysis. No significant differences in acceptability were identified when comparing agents with each other and with placebo. The current findings indicate a pro-cognitive class effect of anti-diabetic agents in AD/MCI. Other anti-diabetic agents should also be investigated in future studies. This study is registered with PROSPERO (CRD42018085967). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Antidotal or protective effects of Curcuma longa (turmeric) and its active ingredient, curcumin, against natural and chemical toxicities: A review.

PubMed

Hosseini, Azar; Hosseinzadeh, Hossein

2018-03-01

Curcuma longa is a rhizomatous perennial herb that belongs to the family Zingiberaceae, native to South Asia and is commonly known as turmeric. It is used as herbal remedy due to the prevalent belief that the plant has medical properties. C. longa possesses different effects such as antioxidant, anti-tumor, antimicrobial, anti-inflammatory, wound healing, and gastroprotective activities. The recent studies have shown that C. longa and curcumin, its important active ingredient, have protective effects against toxic agents. In this review article, we collected in vitro and animal studies which are related to protective effects of turmeric and its active ingredient against natural and chemical toxic agents. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A novel compound DT-010 protects against doxorubicin-induced cardiotoxicity in zebrafish and H9c2 cells by inhibiting reactive oxygen species-mediated apoptotic and autophagic pathways.

PubMed

Tang, Fan; Zhou, Xinhua; Wang, Liang; Shan, Luchen; Li, Chuwen; Zhou, Hefeng; Lee, Simon Ming-Yuen; Hoi, Maggie Pui-Man

2018-02-05

Doxorubicin (Dox) is an effective anti-cancer agent but limited by its cardiotoxicity, thus the search for pharmacological agents for enhancing anti-cancer activities and protecting against cardiotoxicity has been a subject of great interest. We have previously reported the synergistic anti-cancer effects of a novel compound DT-010. In the present study, we further investigated the cardioprotective effects of DT-010 in zebrafish embryos in vivo and the molecular underlying mechanisms in H9c2 cardiomyocytes in vitro. We showed that DT-010 prevented the Dox-induced morphological distortions in the zebrafish heart and the associated cardiac impairments, and especially improved ventricular functions. By using H9c2 cells model, we showed that DT-010 directly inhibited the generation of reactive oxygen species by Dox and protected cell death and cellular damage. We further observed that DT-010 protected against Dox-induced myocardiopathy via inhibiting downstream molecular pathways in response to oxidative stress, including reactive oxygen species-mediated MAPK signaling pathways ERK and JNK, and apoptotic pathways involving the activation of caspase 3, caspase 7, and PARP signaling. Recent studies also suggest the importance of alterations in cardiac autophagy in Dox cardiotoxicity. We further showed that DT-010 could inhibit the induction of autophagosomes formation by Dox via regulating the upstream Akt/AMPK/mTOR signaling. Since Dox-induced cardiotoxicity is multifactorial, our results suggest that multi-functional agent such as DT-010 might be an effective therapeutic agent for combating cardiotoxicity associated with chemotherapeutic agents such as Dox. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessment of antibacterial properties of newer dentin bonding agents: An in vitro study.

PubMed

Sampath, Pavitra B; Hegde, Mithra N; Hegde, Priyadarshini

2011-07-01

To evaluate and compare the antibacterial activity of newer dentin bonding agents on Streptococcus mutans using the direct contact test. Streptococcus mutans was used as test organism and a direct contact test was performed. The dentin bonding agents to be tested were grouped as Group I, Clearfil Protect Bond, Group II, Adper Easy One, and Group III, Prime and Bond NT. For the direct contact test, three microtiter plates consisting of 96 wells each were taken (288 wells). These wells were divided into three groups of 96 wells; 16 wells of a microtiter plate were utilized, of which four were designated as 'A' wells (with the dentin bonding agent and bacterial suspension), another four as 'B' wells (without the dentin bonding agent, but with the bacterial suspension), another four as the 'C' wells (with the tested material, but without bacteria, which served as the negative control), and the remaining four as the 'D' wells (without the dentin bonding agent, which served as the positive control). Each group was treated with their respective bonding agents as per the manufactures instructions. Broth of 15 μL was then transferred from the A wells into an adjacent set of B wells containing fresh medium (215 μL). This resulted in two sets of four wells for each tested material containing an equal volume of liquid medium, so that bacterial growth was monitored both in the presence and in the absence of the tested material. The plate was placed for incubation at 37°C in the microplate reader and the optical density in each well was measured at 600 nm. The readings were taken at regular intervals. (Every 30 minutes for 16 hours). The Dentin bonding agents evaluated in this study showed different inhibitory effects. Clearfil Protect Bond and Prime and Bond NT were most effective, and Adper Easy One was least effective against Streptococcus mutans. The Dentin bonding agents evaluated in this study showed different inhibitory effects. Clearfil Protect Bond and Prime and Bond NT were most effective, and Adper Easy One was the least effective against Streptococcus mutans. Hence, the incorporation of antibacterial agents into the dentin bonding agents may become an essential factor in inhibiting residual bacteria in the cavity and secondary caries.

Nanoplatforms for Detection, Remediation and Protection Against Chem-Bio Warfare

NASA Astrophysics Data System (ADS)

Denkbaş, E. B.; Bayram, C.; Kavaz, D.; Çirak, T.; Demirbilek, M.

Chemical and biological substances have been used as warfare agents by terrorists by varying degree of sophistication. It is critical that these agents be detected in real-time with high level of sensitively, specificity, and accuracy. Many different types of techniques and systems have been developed to detect these agents. But there are some limitations in these conventional techniques and systems. Limitations include the collection, handling and sampling procedures, detection limits, sample transfer, expensive equipment, personnel training, and detection materials. Due to the unique properties such as quantum effect, very high surface/volume ratio, enhanced surface reactivity, conductivity, electrical and magnetic properties of the nanomaterials offer great opportunity to develop very fast, sensitive, accurate and cost effective detection techniques and systems to detect chemical and biological (chem.-bio) warfare agents. Furthermore, surface modification of the materials is very easy and effective way to get functional or smart surfaces to be used as nano-biosensor platform. In that respect many different types of nanomaterials have been developed and used for the detection, remediation and protection, such as gold and silver nanoparticles, quantum dots, Nano chips and arrays, fluorescent polymeric and magnetic nanoparticles, fiber optic and cantilever based nanobiosensors, nanofibrillar nanostructures etc. This study summarizes preparation and characterization of nanotechnology based approaches for the detection of and remediation and protection against chem.-bio warfare agents.

Destruction of chemical warfare agents using metal-organic frameworks

NASA Astrophysics Data System (ADS)

Mondloch, Joseph E.; Katz, Michael J.; Isley, William C., III; Ghosh, Pritha; Liao, Peilin; Bury, Wojciech; Wagner, George W.; Hall, Morgan G.; Decoste, Jared B.; Peterson, Gregory W.; Snurr, Randall Q.; Cramer, Christopher J.; Hupp, Joseph T.; Farha, Omar K.

2015-05-01

Chemical warfare agents containing phosphonate ester bonds are among the most toxic chemicals known to mankind. Recent global military events, such as the conflict and disarmament in Syria, have brought into focus the need to find effective strategies for the rapid destruction of these banned chemicals. Solutions are needed for immediate personal protection (for example, the filtration and catalytic destruction of airborne versions of agents), bulk destruction of chemical weapon stockpiles, protection (via coating) of clothing, equipment and buildings, and containment of agent spills. Solid heterogeneous materials such as modified activated carbon or metal oxides exhibit many desirable characteristics for the destruction of chemical warfare agents. However, low sorptive capacities, low effective active site loadings, deactivation of the active site, slow degradation kinetics, and/or a lack of tailorability offer significant room for improvement in these materials. Here, we report a carefully chosen metal-organic framework (MOF) material featuring high porosity and exceptional chemical stability that is extraordinarily effective for the degradation of nerve agents and their simulants. Experimental and computational evidence points to Lewis-acidic ZrIV ions as the active sites and to their superb accessibility as a defining element of their efficacy.

Destruction of chemical warfare agents using metal-organic frameworks.

PubMed

Mondloch, Joseph E; Katz, Michael J; Isley, William C; Ghosh, Pritha; Liao, Peilin; Bury, Wojciech; Wagner, George W; Hall, Morgan G; DeCoste, Jared B; Peterson, Gregory W; Snurr, Randall Q; Cramer, Christopher J; Hupp, Joseph T; Farha, Omar K

2015-05-01

Chemical warfare agents containing phosphonate ester bonds are among the most toxic chemicals known to mankind. Recent global military events, such as the conflict and disarmament in Syria, have brought into focus the need to find effective strategies for the rapid destruction of these banned chemicals. Solutions are needed for immediate personal protection (for example, the filtration and catalytic destruction of airborne versions of agents), bulk destruction of chemical weapon stockpiles, protection (via coating) of clothing, equipment and buildings, and containment of agent spills. Solid heterogeneous materials such as modified activated carbon or metal oxides exhibit many desirable characteristics for the destruction of chemical warfare agents. However, low sorptive capacities, low effective active site loadings, deactivation of the active site, slow degradation kinetics, and/or a lack of tailorability offer significant room for improvement in these materials. Here, we report a carefully chosen metal-organic framework (MOF) material featuring high porosity and exceptional chemical stability that is extraordinarily effective for the degradation of nerve agents and their simulants. Experimental and computational evidence points to Lewis-acidic Zr(IV) ions as the active sites and to their superb accessibility as a defining element of their efficacy.

Propofol and sodium thiopental protect against MK-801-induced neuronal necrosis in the posterior cingulate/retrosplenial cortex.

PubMed

Jevtovic-Todorovic, V; Wozniak, D F; Powell, S; Olney, J W

2001-09-21

N-Methyl-D-aspartate (NMDA) antagonists act by an anti-excitotoxic action to provide neuroprotection against acute brain injury, but these agents can also cause toxic effects. In low doses they induce reversible neuronal injury, but in higher doses they cause irreversible degeneration of cerebrocortical neurons. GABAmimetic drugs protect against the reversible neurotoxic changes in rat brain. Here we show that two GABAmimetic anesthetic agents--propofol and sodium thiopental--protect against the irreversible neurodegenerative reaction induced by the powerful NMDA antagonist, MK-801.

TREATMENT OF VIRUSES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Polley, J.R.

1963-04-01

A vaccine preparation method was developed for destroying the infectivity of live viruses while retaining the antigenicity. The method comprises exposing the virus to 0.5 to 6 x 10/sup 6/ rad of ionizing radiation (preferably gamma) in the presence of a protective agent. The protective agent is antioxidant in nature and should be used in amounts from 0.05to 0.3% (wt/vol). Histidine and sodium p-aminohippurate are preferred for influenza and mumps viruses respectively. The protective effects of various chemicals on the antigenicity of irradiated influenza A virus are illustrated. (D.L.C.)

Benzamide Derivatives as Protective Agents against the Action of Xenotoxic Agents on Human Cells.

DTIC Science & Technology

1984-05-31

4D-AlI45 396 BENZAMIDE DERIVATIVES AS PROTECTIVE AGENTS AGAINST THE I/i ACTION OF XENOTOXI..(U) OHIO STATE UNIV RESEARCH I FOUNDATION COLUMBUS G E...AS PROTECTIVE AGENTS AGAINST THE ACTION OF XENOTOXIC AGENTS ON HUMAN CELLS CD George E. Milo * Department of Physiological Chemistry and...TITLE (and Subtitle) S. .YPE OF REPORT & PERIOD COVERED Benzamide Derivatives as Protective Agents Annual Scientific Report 5 Against the Action of

Toxicity of the Organophosphate Chemical Warfare Agents GA, GB, and VX: Implications for Public Protection.

PubMed Central

Munro, N

1994-01-01

The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is no evidence that it causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxcity, the nerve agents are not likely to be carcinogens. The overreaching concern with regard to nerve agent exposure is the extraordinarily high acute toxicity of these substances. Furthermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent releaase, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs. Images Figure 2. PMID:9719666

[Medical protection during radiation accidents: some results and lessons of the Chernobyl accident].

PubMed

Legeza, V I; Grebeniuk, A N; Zatsepin, V V

2011-01-01

Actions of medical radiation protection of liquidators of consequences of on Chernobyl atomic power station accident are analysed. It is shown, that during the early period of the accident medical protection of liquidators was provided by administration of radioprotectors, means of prophylaxis: of radioactive iodine incorporation and agent for preventing psychological and emotional stress. When carrying out decontamination and regenerative works, preparations which action is caused by increase of nonspecific resistance of an organism were applied. The lessons taken from the results of the Chernobyl accident, have allowed one to improve the system of medical protection and to introduce in practice new highly effective radioprotective agents.

Sulfur compounds in therapy: Radiation-protective agents, amphetamines, and mucopolysaccharide sulfation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foye, W.O.

1992-09-01

Sulfur-containing compounds have been used in the search for whole-body radiation-protective compounds, in the design of amphetamine derivatives that retain appetite-suppressive effects but lack most behavioral effects characteristic of amphetamines, and in the search for the cause of kidney stone formation in recurrently stoneforming patients. Organic synthetic procedures were used to prepare radiation-protective compounds having a variety of sulfur-containing functional groups, and to prepare amphetamine derivatives having electron-attracting sulfur functions. In the case of the kidney stone causation research, isolation of urinary mucopolysaccharides (MPS) from recurrently stoneforming patients was carried out and the extent of sulfation of the MPS wasmore » determined by electrophoresis. Whole-body radiation-protective agents with a high degree of protection against lethal doses of gamma-radiation in mice were found in a series of quinolinium and pyridinium bis(methylthio) and methylthio amino derivatives. Mechanism studies showed that the copper complexes of these agents mimicked the beneficial action of superoxide dismutase. Electron-attracting sulfur-containing functions on amphetamine nitrogen, as well as 4'-amino nitrogen provided amphetamine derivatives with good appetite-suppressant effects and few or no adverse behavioral effects. Higher than normal levels of sulfation of the urinary MPS of stone formers suggested a cause for recurrent kidney stone formation. A sulfation inhibitor was found to prevent recurrence of stone formation and inhibit growth of existing stones. The inclusion of various sulfur-containing functions in organic molecules yielded compounds having whole-body radiation protection from lethal doses of gamma-radiation in animals. The presence of electron-attracting sulfur functions in amphetamine gave derivatives that retained appetite-suppressant effects and eliminated most adverse behavioral effects.« less

Coinjection of a vaccine and anti-viral agents can provide fast-acting protection from foot-and-mouth disease.

PubMed

You, Su-Hwa; Kim, Taeseong; Choi, Joo-Hyung; Park, Gundo; Lee, Kwang-Nyeong; Kim, Byounghan; Lee, Myoung-Heon; Kim, Hyun-Soo; Kim, Su-Mi; Park, Jong-Hyeon

2017-07-01

Foot-and-mouth disease (FMD) is the cause of an economically devastating animal disease. With commercial inactivated FMD vaccines, the protection against FMD virus (FMDV) begins a minimum of 4 days post vaccination (dpv). Therefore, antiviral agents could be proposed for rapid protection and to reduce the spread of FMDV during outbreaks until vaccine-induced protective immunity occurs. In previous studies, we have developed two recombinant adenoviruses that simultaneously express porcine interferon-α and interferon-γ (Ad-porcine IFN-αγ) and multiple siRNAs that target the non-structural protein-regions of FMDV (Ad-3siRNA), and we have shown that the combination of the two antiviral agents (referred to here as Ad combination) induced robust protection against FMDV in pigs. In an attempt to provide complete protection against FMDV, we co-administered Ad combination and the FMD vaccine to mice and pigs. In the C57BL/6 mice model, we observed rapid and continuous protection against homologous FMDV challenge from 1 to 3 dpv-the period in which vaccine-mediated immunity is absent. In the pig experiments, we found that most of the pigs (five out of six) that received vaccine + Ad combination and were challenged with FMDV at 1 or 2 dpv were clinically protected from FMDV. In addition, most of the pigs that received vaccine + Ad combination and all pigs inoculated with the vaccine only were clinically protected from an FMDV challenge at 7 dpv. We believe that the antiviral agent ensures early protection from FMDV, and the vaccine participates in protection after 7 dpv. Therefore, we can say that the combination of the FMD vaccine and effective antiviral agents may offer both fast-acting and continuous protection against FMDV. In further studies, we plan to design coadministration of Ad combination and novel vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevention of shockwave induced functional and morphological alterations: an overview.

PubMed

Sarica, Kemal; Yencilek, Faruk

2008-03-01

Experimental as well as clinical findings reported in the literature suggest that treatment with shock wave lithotripsy (SWL) causes renal parenchymal damage mainly by generating free radicals through ischaemia/reperfusion injury mechanism. Although SWL-induced renal damage is well tolerated in the majority of healthy cases with no permanent functional and/or morphologic side effects, a subset of patients with certain risk factors requires close attention on this aspect among which the ones with pre-existing renal disorders, urinary tract infection, previous lithotripsy history and solitary kidneys could be mentioned. It is clear that in such patients lowering the number of shock waves (per session) could be beneficial and has been applied by the physicians as the first practical step of diminishing SWL induced parenchymal damage. On the other hand, taking the injurious effects of high energy shock wave (HESW) induced free radical formation on renal parenchyma and subsequent histopathologic alterations into account, physicians searched for some protective agents in an attempt to prevent or at least to limit the extent of the functional as well as the morphologic alterations. Among these agents calcium channel blocking agents (verapamil and nifedipine), antioxidant agents (allopurinol, vitamin E and selenium) and potassium citrate have been used to minimize these adverse effects. Additionally, therapeutic application of these agents on reducing stone recurrence particularly after SWL will gain more importance in the future in order to limit new stone formation in these cases. Lastly, as experimental and clinical studies have demonstrated, combination of anti-oxidants with free radical scavengers may provide superior renal protection against shock wave induced trauma. However, we believe that further investigations are certainly needed to determine the dose-response relationship between the damaging effects of SWL application and the protective role of these agents.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akatsuchi, Y.

Mice were x irradiated by whole-body single doses of 700 r (lethal dose). The administration of phenylephrine chloride, naphazoline, tetrahydrozoline chloride, and noradrenaline gave considerable protection against the lethal effect, when an optimal dose of each agent was given. Cocaine chloride, histamine chloride, or adrenaline chloride gave moderate protection. No protective effect was seen after the administration of ephedrine chloride or diphenhydramine. (Abstr. Japan Med., 2, No. 1, Jan. 1962)

Cisplatin impairs rat liver mitochondrial functions by inducing changes on membrane ion permeability: prevention by thiol group protecting agents.

PubMed

Custódio, José B A; Cardoso, Carla M P; Santos, Maria S; Almeida, Leonor M; Vicente, Joaquim A F; Fernandes, Maria A S

2009-05-02

Cisplatin (CisPt) is the most important platinum anticancer drug widely used in the treatment of head, neck, ovarian and testicular cancers. However, the mechanisms by which CisPt induces cytotoxicity, namely hepatotoxicity, are not completely understood. The goal of this study was to investigate the influence of CisPt on rat liver mitochondrial functions (Ca(2+)-induced mitochondrial permeability transition (MPT), mitochondrial bioenergetics, and mitochondrial oxidative stress) to better understand the mechanism underlying its hepatotoxicity. The effect of thiol group protecting agents and some antioxidants against CisPt-induced mitochondrial damage was also investigated. Treatment of rat liver mitochondria with CisPt (20nmol/mg protein) induced Ca(2+)-dependent mitochondrial swelling, depolarization of membrane potential (DeltaPsi), Ca(2+) release, and NAD(P)H fluorescence intensity decay. These effects were prevented by cyclosporine A (CyA), a potent and specific inhibitor of the MPT. In the concentration range of up to 40nmol/mg protein, CisPt slightly inhibited state 3 and stimulated state 2 and state 4 respiration rates using succinate as respiratory substrate. The respiratory indexes, respiratory control ratio (RCR) and ADP/O ratios, the DeltaPsi, and the ADP phosphorylation rate were also depressed. CisPt induced mitochondrial inner membrane permeabilization to protons (proton leak) but did not induce significant changes on mitochondrial H(2)O(2) generation. All the effects induced by CisPt on rat liver mitochondria were prevented by thiol group protecting agents namely, glutathione (GSH), dithiothreitol (DTT), N-acetyl-L-cysteine (NAC) and cysteine (CYS), whereas superoxide-dismutase (SOD), catalase (CAT) and ascorbate (ASC) were without effect. In conclusion, the anticancer drug CisPt: (1) increases the sensitivity of mitochondria to Ca(2+)-induced MPT; (2) interferes with mitochondrial bioenergetics by increasing mitochondrial inner membrane permeabilization to H(+); (3) does not significantly affect H(2)O(2) generation by mitochondria; (4) its mitochondrial damaging effects are protected by thiol group protecting agents. Based on these conclusions, it is possible to hypothesise that small changes on the redox-status of thiol groups, affecting membrane permeability to cations (Ca(2+) and H(+)) underlie CisPt-induced liver mitochondrial damage, putatively responsible for its hepatotoxicity. Therefore, we propose that CisPt-induced mitochondrial damage and consequent hepatotoxicity could be prevented by using thiol group protecting agents as therapeutic adjuvants.

Toxicity of the organophosphate chemical warfare agents GA, GB, and VX: Implications for public protection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Munro, N.B.; Ambrose, K.R.; Watson, A.P.

1994-01-01

The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is not evidence that itmore » causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxicity, the nerve agent exposure is the extraordinarily high acute toxicity of these substances. Futhermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent release, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs. 187 refs., 3 figs., 7 tabs.« less

A Histological Assessment of Lung Injury in Rats Exposed to Inhaled Sulfur Mustard across Dose and Time

DTIC Science & Technology

2015-06-01

J (2008) Health effects of exposure to vesicant agents. In: Chemical Warfare Agents – Chemistry , Pharmacology, Toxicology, and Therapeutics. Eds...sulfphide and the protective effect of flavonoids . Toxicology 69: 35-42. Wada S, Nishimoto Y, Miyanishi M, Kambe S, Miller R W(1968) Mustard gas as

Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting.

PubMed

Zilbermintz, Leeor; Leonardi, William; Jeong, Sun-Young; Sjodt, Megan; McComb, Ryan; Ho, Chi-Lee C; Retterer, Cary; Gharaibeh, Dima; Zamani, Rouzbeh; Soloveva, Veronica; Bavari, Sina; Levitin, Anastasia; West, Joel; Bradley, Kenneth A; Clubb, Robert T; Cohen, Stanley N; Gupta, Vivek; Martchenko, Mikhail

2015-08-27

A longstanding and still-increasing threat to the effective treatment of infectious diseases is resistance to antimicrobial countermeasures. Potentially, the targeting of host proteins and pathways essential for the detrimental effects of pathogens offers an approach that may discover broad-spectrum anti-pathogen countermeasures and circumvent the effects of pathogen mutations leading to resistance. Here we report implementation of a strategy for discovering broad-spectrum host-oriented therapies against multiple pathogenic agents by multiplex screening of drugs for protection against the detrimental effects of multiple pathogens, identification of host cell pathways inhibited by the drug, and screening for effects of the agent on other pathogens exploiting the same pathway. We show that a clinically used antimalarial drug, Amodiaquine, discovered by this strategy, protects host cells against infection by multiple toxins and viruses by inhibiting host cathepsin B. Our results reveal the practicality of discovering broadly acting anti-pathogen countermeasures that target host proteins exploited by pathogens.

Biological alterations and self-reported symptoms among insecticides-exposed workers in Burkina Faso.

PubMed

Toe, Adama M; Ilboudo, Sylvain; Ouedraogo, Moustapha; Guissou, Pierre I

2012-03-01

Occupationally exposed workers, farm workers and plant protection agents in the Sahel region of Burkina Faso were interviewed to assess adverse health effects of insecticides. The subjects were also examined for changes in both hematological and biochemical parameters. The prevalence of liver and kidney dysfunction was found to be quite high among insecticide applicators, especially among plant protection agents. The prevalence of biochemical alterations seems to be correlated to the frequency of insecticide use. However, no significant differences were found between the hematological parameters among farm workers and plant protection agents. The hematological parameters of all the insecticide applicators were normal. The great majority of insecticide applicators (85%) reported symptoms related to insecticide exposure. The use of insecticides in the agriculture of Burkina Faso is threatening to human health.

Chemical Surface Washing Agents for Oil Spills: Update State-of-the-Art on Mechanisms of Action and Evaluation of Two Laboratory Effectiveness Tests.

EPA Science Inventory

Chemical surface washing agents are formulations designed to help release stranded oil from shoreline substrates.The U.S. Environmental Protection Agency (EPA), in response to the Oil Pollution Act of 1990, Initiated study of these cleaning agents. The project summarized here had...

Protective effect of conditioning agents on Afro-ethnic hair chemically treated with thioglycolate-based straightening emulsion.

PubMed

Dias, Tania Cristina de Sá; Baby, André Rolim; Kaneko, Telma Mary; Velasco, Maria Valéria Robles

2008-06-01

Straightening is a chemical process by which excessively curly hair is straightened in an irreversible way. Generally, products are formulated as emulsions with high pH value (9.0-12.0), which, after applied on hair, cause considerable damage, making it dry and fragile. This research work evaluated the protective effect of lauryl PEG/PPG-18/18 methicone, cyclopentasiloxane (and) PEG-12 dimethicone cross-polymer, jojoba oil, and aqua (and) cystine bis-PG propyl silanetriol, as conditioning agents, on Afro-ethnic hair locks treated with thioglycolate-based straightening emulsions by protein loss, combability, and traction to rupture. Standard Afro-ethnic hair locks were prepared following a protocol for straightening emulsion application. Considering the assays performed, the addition of conditioning agents to the straightening emulsion with ammonium thioglycolate benefited the hair fiber, thus diminishing protein loss, protecting the hair thread, and improving resistance to breakage. Jojoba oil and lauryl PEG/PPG-18/18 methicone were the conditioning agents that presented the best results. Straightening emulsions with ammonium thioglycolate containing aqua (and) cystine bis-PG propyl silanetriol and cyclopentasiloxane (and) PEG-12 dimethicone cross-polymer were the ones that provided higher breakage resistance of the thread.

Effect of both protective and reducing agents in the synthesis of multicolor silver nanoparticles

NASA Astrophysics Data System (ADS)

Rivero, Pedro Jose; Goicoechea, Javier; Urrutia, Aitor; Arregui, Francisco Javier

2013-02-01

In this paper, the influence of variable molar ratios between reducing and loading agents (1:100, 1:50, 1:20, 1:10, 1:5, 1:2, 1:1, 2:1) and between protective and loading agents (0.3:1, 0.75:1, 1.5:1, 3:1, 7.5:1, 30:1, 75:1) in the synthesis of silver nanoparticles by chemical reduction has been evaluated to obtain multicolor nanoparticles with a high stability in time. The protective agent poly(acrylic acid, sodium salt) (PAA) and reducing agent dimethylaminoborane (DMAB) play a key role in the formation of the resultant color. Evolution of the optical absorption bands of the silver nanoparticles as a function of PAA and DMAB molar ratios made it possible to confirm the presence of silver nanoparticles or clusters with a specific shape. The results reveal that a wide range of colors (violet, blue, green, brown, yellow, red, orange), sizes (from nanometer to micrometer), and shapes (cubic, rod, triangle, hexagonal, spherical) can be perfectly tuned by means of a fine control of the PAA and DMAB molar concentrations.

Black Seed (Nigella Sativa) and its Constituent Thymoquinone as an Antidote or a Protective Agent Against Natural or Chemical Toxicities

PubMed Central

Tavakkoli, Alireza; Ahmadi, Ali; Razavi, Bibi Marjan; Hosseinzadeh, Hossein

2017-01-01

Nigella sativa (N. sativa), which belongs to the botanical family of Ranunculaceae, is a widely used medicinal plant all over the world. N. sativa seeds and oil have been used in the treatment of different diseases. Various studies on N. sativa have been carried out and a broad spectrum of its pharmacological actions have been established which include antioxidant, antidiabetic, anticancer, antitussive, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, and bronchodilator. This is also indicated that the majority of the therapeutic effects of N. sativa are due to the presence of thymoquinone (TQ) that is the main bioactive constituent of the essential oil. According to several lines of evidence, the protective effects of this plant and its main constituent in different tissues including brain, heart, liver, kidney, and lung have been proved against some toxic agents either natural or chemical toxins in animal studies. In this review article, several in-vitro and animal studies in scientific databases which investigate the antidotal and protective effects of N. sativa and its main constituents against natural and chemical induced toxicities are introduced. Because human reports are rare, further studies are required to determine the efficacy of this plant as an antidote or protective agent in human intoxication. PMID:29844772

Neurotensin protects pancreatic beta cells from apoptosis.

PubMed

Coppola, Thierry; Béraud-Dufour, Sophie; Antoine, Aurélie; Vincent, Jean-Pierre; Mazella, Jean

2008-01-01

The survival of pancreatic beta cells depends on the balance between external cytotoxic and protective molecular systems. The neuropeptide neurotensin (NT) has been shown to regulate certain functions of the endocrine pancreas including insulin and glucagon release. However, the mechanism of action of NT as well as the identification of receptors involved in the pancreatic functions of the peptide remained to be studied. We demonstrate here that NT is an efficient protective agent of pancreatic beta cells against cytotoxic agents. Both beta-TC3 and INS-1E cell lines and the mouse pancreatic islet cells express the three known NT receptors. The incubation of beta cells with NT protects cells from apoptosis induced either by staurosporine or by IL-1beta. In beta-TC3 cells, NT activates both MAP and PI-3 kinases pathways and strongly reduces the staurosporine or the Il-1beta-induced caspase-3 activity by a mechanism involving Akt activation. The NTSR2 agonist levocabastine displays the same protective effect than NT whereas the NTSR1 antagonist is unable to block the effect of NT suggesting the predominant involvement of the NTSR2 in the action of NT on beta cells. These results clearly indicate for the first time that NT is able to protect endocrine beta cells from external cytotoxic agents, a role well correlated with its release in the circulation after a meal.

Emergent Behavior of Coupled Barrier Island - Resort Systems

NASA Astrophysics Data System (ADS)

McNamara, D. E.; Werner, B. T.

2004-12-01

Barrier islands are attractive sites for resorts. Natural barrier islands experience beach erosion and island overwash during storms, beach accretion and dune building during inter-storm periods, and migration up the continental shelf as sea level rises. Beach replenishment, artificial dune building, seawalls, jetties and groins have been somewhat effective in protecting resorts against erosion and overwash during storms, but it is unknown how the coupled system will respond to long-term sea level rise. We investigate coupled barrier island - resort systems using an agent-based model with three components: natural barrier islands divided into a series of alongshore cells; resorts controlled by markets for tourism and hotel purchases; and coupling via storm damage to resorts and resort protection by government agents. Modeled barrier islands change by beach erosion, island overwash and inlet cutting during storms, and beach accretion, tidal delta growth and dune and vegetation growth between storms. In the resort hotel market, developer agents build hotels and hotel owning agents purchase them using predictions of future revenue and property appreciation, with the goal of maximizing discounted utility. In the tourism market, hotel owning agents set room rental prices to maximize profit and tourist agents choose vacation destinations maximizing a utility based on beach width, price and word-of-mouth. Government agents build seawalls, groins and jetties, and widen the beach and build up dunes by adding sand to protect resorts from storms, enhance beach quality, and maximize resort revenue. Results indicate that barrier islands and resorts evolve in a coupled manner to resort size saturation, with resorts protected against small-to-intermediate-scale storms under fairly stable sea level. Under extended, rapidly rising sea level, protection measures enhance the effect of large storms, leading to emergent behavior in the form of limit cycles or barrier submergence, depending on the relative rates of resort recovery from storms and sea level rise. The model is applied to Ocean City, Maryland and neighboring undeveloped Assateague Island National Seashore. Supported by the National Science Foundation, Geology and Paleontology Program, and the Andrew W. Mellon Foundation

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents.

PubMed

Albuquerque, Edson X; Pereira, Edna F R; Aracava, Yasco; Fawcett, William P; Oliveira, Maristela; Randall, William R; Hamilton, Tracey A; Kan, Robert K; Romano, James A; Adler, Michael

2006-08-29

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer's disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning.

Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents

PubMed Central

Albuquerque, Edson X.; Pereira, Edna F. R.; Aracava, Yasco; Fawcett, William P.; Oliveira, Maristela; Randall, William R.; Hamilton, Tracey A.; Kan, Robert K.; Romano, James A.; Adler, Michael

2006-01-01

The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer’s disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning. PMID:16914529

Redox properties of ginger extracts: Perspectives of use of Zingiber officinale Rosc. as antidiabetic agent

PubMed Central

Cupáková, Máriá; Ťažký, Anton; Mičová, Júlia; Kolek, Emil; Košt'álová, Daniela

2013-01-01

In traditional medicine, several medicinal plants or their extracts have been used to treat diabetes. Zingiber officinale Roscoe, known commonly as ginger, is consumed worldwide in cookeries as a spice and flavouring agent. It has been used as the spice and medicine for thousands of years. The present study was undertaken to investigate the potential protective effect of Zingiber officinale Rosc. in a model of oxidative damage to pancreatic β cells. The free radical scavenging activities and composition of the isolated n-hexane and ethanolic extracts were confronted with their protective, antioxidant and cytotoxic effects in INS-1E β cells. Unlike the n-hexane extract (exerting, paradoxically, stronger antiradical capacity), both low cytotoxicity and remarkable protective effects on β cell viability, followed by lowering oxidative stress markers were found for the ethanolic extract Zingiber officinale Rosc. The present study is the first pilot study to assess the protective potential of Zingiber officinale Rosc. in a model of cytotoxic conditions imposed by diabetes in β cells. PMID:24170976

Redox properties of ginger extracts: Perspectives of use of Zingiber officinale Rosc. as antidiabetic agent.

PubMed

Račková, Lucia; Cupáková, Máriá; Tažký, Anton; Mičová, Júlia; Kolek, Emil; Košt'álová, Daniela

2013-03-01

In traditional medicine, several medicinal plants or their extracts have been used to treat diabetes. Zingiber officinale Roscoe, known commonly as ginger, is consumed worldwide in cookeries as a spice and flavouring agent. It has been used as the spice and medicine for thousands of years. The present study was undertaken to investigate the potential protective effect of Zingiber officinale Rosc. in a model of oxidative damage to pancreatic β cells. The free radical scavenging activities and composition of the isolated n-hexane and ethanolic extracts were confronted with their protective, antioxidant and cytotoxic effects in INS-1E β cells. Unlike the n-hexane extract (exerting, paradoxically, stronger antiradical capacity), both low cytotoxicity and remarkable protective effects on β cell viability, followed by lowering oxidative stress markers were found for the ethanolic extract Zingiber officinale Rosc. The present study is the first pilot study to assess the protective potential of Zingiber officinale Rosc. in a model of cytotoxic conditions imposed by diabetes in β cells.

19 CFR 191.9 - Agency.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED... merchandise while it is in the agent's custody; and (vi) The period that the contract is in effect. (2... of manufacturing or production operations performed by the agent; (iv) Total quantity and description...

Heat inactivation of poliovirus in wastewater sludge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, R.L.; Ashley, C.S.; Moseley, R.H.

1976-09-01

The effect of raw and anaerobically digested sludge on heat inactivation of poliovirus was investigated. Raw sludge was found to be very protective of poliovirus plaque-forming ability at all temperatures studied, but digested sludge had variable effects that were highly dependent upon the experimental conditions. In low concentrations and at relatively low inactivation temperatures, digested sludge is nearly as protective of poliovirus as raw sludge. However, at higher temperatures and concentrations, digested sludge caused a significant acceleration of poliovirus inactivation. The difference between the protective capability of raw and digested sludge is not due to loss of protective material, becausemore » this component is present in the solids of digested sludge as well as in those of raw sludge. Instead, the difference is due to a virucidal agent acquired during digestion. Addition of this agent to the solids of either raw or digested sludge reverses the protective potential of these solids during heat treatment of poliovirus.« less

Biological alterations and self-reported symptoms among insecticides-exposed workers in Burkina Faso

PubMed Central

Toe, Adama M.; Ilboudo, Sylvain; Ouedraogo, Moustapha; Guissou, Pierre I.

2012-01-01

Occupationally exposed workers, farm workers and plant protection agents in the Sahel region of Burkina Faso were interviewed to assess adverse health effects of insecticides. The subjects were also examined for changes in both hematological and biochemical parameters. The prevalence of liver and kidney dysfunction was found to be quite high among insecticide applicators, especially among plant protection agents. The prevalence of biochemical alterations seems to be correlated to the frequency of insecticide use. However, no significant differences were found between the hematological parameters among farm workers and plant protection agents. The hematological parameters of all the insecticide applicators were normal. The great majority of insecticide applicators (85%) reported symptoms related to insecticide exposure. The use of insecticides in the agriculture of Burkina Faso is threatening to human health. PMID:22783149

Ischemia-Reperfusion Injury and Volatile Anesthetics

PubMed Central

Erturk, Engin

2014-01-01

Ischemia-reperfusion injury (IRI) is induced as a result of reentry of the blood and oxygen to ischemic tissue. Antioxidant and some other drugs have protective effect on IRI. In many surgeries and clinical conditions IRI is counteract inevitable. Some anesthetic agents may have a protective role in this procedure. It is known that inhalational anesthetics possess protective effects against IRI. In this review the mechanism of preventive effects of volatile anesthetics and different ischemia-reperfusion models are discussed. PMID:24524079

Gastric cytoprotective anti-ulcerogenic actions of hydroxychalcones in rats.

PubMed

Yamamoto, K; Kakegawa, H; Ueda, H; Matsumoto, H; Sudo, T; Miki, T; Satoh, T

1992-10-01

The preventive effects of hydroxychalcone derivatives on ulcer formation induced by severe necrotizing agents such as 60% ethanol in 150 mM HCl (HCl-ethanol) and 0.2 N NaOH in rats were examined. Among the compounds tested, 2',4'-dihydroxychalcone gave the strongest activity in both experimental models and protected the gastric mucosa from the insult of either necrotizing agent at oral doses ranging from 1 to 10 mg/kg, as evidenced by a dose-related reduction in the ulcer index. The mucosal protective activity of 2',4'-dihydroxychalcone was not affected by pretreatment with indomethacin (5 mg/kg, s.c.). To investigate the detailed mechanism of the mucosal protective action of 2',4'-dihydroxychalcone, its inhibitory effects on the decrease in the hexosamine content from the gastric mucus induced by HCl-ethanol were studied by using it in combination with a dye, Alcian blue. As a result, 2',4'-dihydroxychalcone at an oral dose of 10 mg/kg inhibited the decrease in the dye-recovery from the gastric mucus induced by HCl-ethanol. PGE2 at an oral dose of 0.1 mg/kg exhibited a similar action. These results established that 2',4'-dihydroxychalcone is a potent cytoprotective agent similar to PGE2 effectively preventing gastric ulcer formation induced by strong necrotizing agents and seems to suggest that this compound protects the stomach against its own peptic secretions by reinforcement of gastric resistances. In fact, 2',4'-dihydroxychalcone prevented ulcer formation induced by water-immersion stress in rats and also showed a marked enhancement of the healing of acetic acid-induced gastric ulcers in rats.

Influence of Surfactants and Fluoride against Enamel Erosion.

PubMed

Zanatta, Rayssa Ferreira; Ávila, Daniele Mara da Silva; Miyamoto, Karen Mayumi; Torres, Carlos Rocha Gomes; Borges, Alessandra Bühler

2018-06-06

This study investigated the effect of surfactants associated with sodium fluoride (NaF) on enamel erosion prevention, using an erosion-remineralization in vitro model. Sodium lauryl sulfate (SLS), polysorbate 20 (P20), and cocoamidopropyl betaine (CAPB) were tested, at concentrations of 1.0 and 1.5%, and associated or not with NaF (275 ppm). The control groups were distilled water and the NaF solution. Bovine enamel samples (n = 12) were prepared and submitted to a 5-day cycling model: acid challenge (0.3% citric acid, pH 2.6, 4×/day), human saliva (2 h, 4×/day), and the treatment solutions (2 min, 2×/day). The protective potential of the agents against initial erosion was assessed by microhardness and the surface loss by profilometry. Enamel surface wettability was determined by goniometry, protein adsorption was measured by spectroscopy (FTIR), and the KOH-soluble fluoride was quantified. Goniometry showed that SLS and CAPB increased enamel wettability. No differences were found among the surfactants regarding protein adsorption. Microhardness showed that SLS reduced NaF protection. P20 (1 and 1.5%) and CAPB 1.5% presented a protective effect, but lower than the NaF solution. Profilometry showed that CAPB protected enamel, but no agent associated with NaF promoted a higher protection than the NaF solution alone. KOH-soluble fluoride analysis showed that all surfactants reduced the fluoride adsorption on the enamel surface. Therefore, the surfactants tested (except for P20) changed the enamel surface energy. The SLS decreased the protective potential of NaF on initial erosion, but no tested agent interfered with the protective effect of NaF on enamel erosive wear. © 2018 S. Karger AG, Basel.

Radiation damage and radioprotectants: new concepts in the era of molecular medicine

PubMed Central

Koukourakis, M I

2012-01-01

Exposure to ionising radiation results in mutagenesis and cell death, and the clinical manifestations depend on the dose and the involved body area. Reducing carcinogenesis in patients treated with radiotherapy, exposed to diagnostic radiation or who are in certain professional groups is mandatory. The prevention or treatment of early and late radiotherapy effects would improve quality of life and increase cancer curability by intensifying therapies. Experimental and clinical data have given rise to new concepts and a large pool of chemical and molecular agents that could be effective in the protection and treatment of radiation damage. To date, amifostine is the only drug recommended as an effective radioprotectant. This review identifies five distinct types of radiation damage (I, cellular depletion; II, reactive gene activation; III, tissue disorganisation; IV, stochastic effects; V, bystander effects) and classifies the radioprotective agents into five relevant categories (A, protectants against all types of radiation effects; B, death pathway modulators; C, blockers of inflammation, chemotaxis and autocrine/paracrine pathways; D, antimutagenic keepers of genomic integrity; E, agents that block bystander effects). The necessity of establishing and funding central committees that guide systematic clinical research into evaluating the novel agents revealed in the era of molecular medicine is stressed. PMID:22294702

Perspectives on the Use of Scopolamine as an Adjunct Treatment to Enhance Survival Following Organophosphorus Nerve Agent Poisoning

DTIC Science & Technology

2010-11-01

particular nerve agent and oxime uti- lized in the treatment regimen. Atropine is the universal treatment for organophospho- rus anticholinesterase poisoning...general, to the recovery of AChE activity either through decarbamylation of PB protected enzyme or by use of an effective oxime. The results against...this protected enzyme in the first few minutes after intoxication and treat- ment provides sufficient enzyme activity to sustain survival.̂ ’"* A

Privacy Preservation in Distributed Subgradient Optimization Algorithms.

PubMed

Lou, Youcheng; Yu, Lean; Wang, Shouyang; Yi, Peng

2017-07-31

In this paper, some privacy-preserving features for distributed subgradient optimization algorithms are considered. Most of the existing distributed algorithms focus mainly on the algorithm design and convergence analysis, but not the protection of agents' privacy. Privacy is becoming an increasingly important issue in applications involving sensitive information. In this paper, we first show that the distributed subgradient synchronous homogeneous-stepsize algorithm is not privacy preserving in the sense that the malicious agent can asymptotically discover other agents' subgradients by transmitting untrue estimates to its neighbors. Then a distributed subgradient asynchronous heterogeneous-stepsize projection algorithm is proposed and accordingly its convergence and optimality is established. In contrast to the synchronous homogeneous-stepsize algorithm, in the new algorithm agents make their optimization updates asynchronously with heterogeneous stepsizes. The introduced two mechanisms of projection operation and asynchronous heterogeneous-stepsize optimization can guarantee that agents' privacy can be effectively protected.

78 FR 69854 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-21

... undetermined agents, undetermined sources, undetermined transmission, or undetermined risk factors. These EEIs... transmission, or risk factors to effectively implement rapid prevention and control measures to protect the...; data are analyzed to determine the agents, sources, modes of transmission, or risk factors so that...

Protective effects of total saponins from stem and leaf of Panax ginseng against cyclophosphamide-induced genotoxicity and apoptosis in mouse bone marrow cells and peripheral lymphocyte cells.

PubMed

Zhang, Qiu Hua; Wu, Chun Fu; Duan, Lian; Yang, Jing Yu

2008-01-01

Cyclophosphamide (CP), commonly used anti-cancer, induces oxidative stress and is cytotoxic to normal cells. It is very important to choice the protective agent combined CP to reduce the side effects in cancer treatment. Ginsenosides are biological active constituents of Panax ginseng C.A. Meyer that acts as the tonic agent for the cancer patients to reduce the side effects in the clinic application. Because CP is a pro-oxidant agent and induces oxidative stress by the generation of free radicals to decrease the activities of anti-oxidant enzymes, the protective effects of the total saponins from stem and leaf of P. ginseng C.A. Meyer (TSPG) act as an anti-oxidant agent against the decreased anti-oxidant enzymes, the genotoxicity and apoptosis induced by CP was carried out. The alkaline single cell gel electrophoresis was employed to detect DNA damage; flow cytometry assay and AO/EB staining assay were employed to measure cell apoptosis; the enzymatic anti-oxidants (T-SOD, CAT and GPx) and non-enzymatic anti-oxidant (GSH) were measured by the various colorimetric methods. CP induced the significant DNA damage in mouse peripheral lymphocytes in time- and dose-dependent manners, inhibited the activities of T-SOD, GPx and CAT, and decreased the contents of GSH in mouse blood, triggered bone marrow cell apoptosis at 6 and 12h. TSPG significantly reduced CP-induced DNA damages in bone marrow cells and peripheral lymphocyte cells, antagonized CP-induced reduction of T-SOD, GPx, CAT activities and the GSH contents, decreased the bone marrow cell apoptosis induced by CP. TSPG, significantly reduced the genotoxicity of CP in bone marrow cells and peripheral lymphocyte cells, and decreased the apoptotic cell number induced by CP in bone marrow cells. The effects of TSPG on T-SOD, GPx, CAT activities and GSH contents might partially contribute to its protective effects on CP-induced cell toxicities.

Personal protection during resuscitation of casualties contaminated with chemical or biological warfare agents--a survey of medical first responders.

PubMed

Brinker, Andrea; Prior, Kate; Schumacher, Jan

2009-01-01

The threat of mass casualties caused by an unconventional terrorist attack is a challenge for the public health system, with special implications for emergency medicine, anesthesia, and intensive care. Advanced life support of patients injured by chemical or biological warfare agents requires an adequate level of personal protection. The aim of this study was to evaluate the personal protection knowledge of emergency physicians and anesthetists who would be at the frontline of the initial health response to a chemical/biological warfare agent incident. After institutional review board approval, knowledge of personal protection measures among emergency medicine (n = 28) and anesthetics (n = 47) specialty registrars in the South Thames Region of the United Kingdom was surveyed using a standardized questionnaire. Participants were asked for the recommended level of personal protection if a chemical/biological warfare agent(s) casualty required advanced life support in the designated hospital resuscitation area. The best awareness within both groups was regarding severe acute respiratory syndrome, and fair knowledge was found regarding anthrax, plague, Ebola, and smallpox. In both groups, knowledge about personal protection requirements against chemical warfare agents was limited. Knowledge about personal protection measures for biological agents was acceptable, but was limited for chemical warfare agents. The results highlight the need to improve training and education regarding personal protection measures for medical first receivers.

The Effect of CAMBRA Agents on Fracture Strength of Lithium Disilicate Crowns

NASA Astrophysics Data System (ADS)

Sinada, Naif

The Caries Management By Risk Assessment (CAMBRA) protocol outlines an approach in which certain agents can be used to serve as protective factors toward the management of dental caries. In this study, the effects of particular CAMBRA agents on the fracture strength of lithium disilicate ceramics (commonly used in dentistry) are studied. While Chlorhexidine exhibited no effects on the fracture strength of these ceramics, Prevident showed a decrease in the fracture strength of all the ceramics studied. These results indicate that clinicians should proceed with caution when using these CAMBRA agents in patients restored with lithium disilicate ceramics. Further studies on the particular mechanisms whereby this reduction in fracture strength occurs are indicated.

Comparison of the antibacterial activity of different self-etching primers and adhesives.

PubMed

Korkmaz, Yonca; Ozalp, Meral; Attar, Nuray

2008-11-01

The aim of this study was to evaluate the antibacterial effects of different one-step and two-step self-etching primer/adhesives on Streptococcus mutans (S. mutans), Lactobacillus casei (L. casei), and Lactobacillus acidophilus (L. acidophilus). The antibacterial effects of Clearfil Protect Bond Primer and Bonding agent; AdheSE Primer and Bonding agent; Adper Prompt L-Pop; Futurabond NR; Clearfil Tri S Bond; and Cervitec (positive control, 1% chlorhexidine varnish) were tested against standard strains of S. mutans, L. Casei, and L. acidophilus using the disk diffusion method. Standard filter paper disks (n=5) impregnated with 20 microL of each material were prepared. After incubation at 37 masculineC for 48 hours in a 5-10% CO2 atmosphere, the diameter of inhibition zones were measured in millimeters. Data were analyzed using one way analysis of variance (ANOVA) and multivariate analysis of variance (MANOVA). Duncan's Multiple Range Test was used for pairwise comparison. The size of inhibition zones produced by primer/adhesives varied among the brands. AdheSE Primer: S. mutans (20.6+/-1.51); L. casei (14.8+/-1.78); L. acidophilus (11.4+/-0.54). Adper Prompt L-Pop: S. mutans (19.6+/-1.51); L. casei (13.8+/-1.64); L. acidophilus (13.8+/-1.09). Cervitec: S. mutans (23+/-0.00); L. casei (27+/-0.70); L. acidophilus (22.4+/-0.54). Clearfil Protect Bond Primer: S. mutans (17+/-0.00); L. casei (17.6+/-0.54); L. acidophilus (22.4+/-0.54). Futurabond NR was found effective only against S. mutans (14.6+/-1.67). Of all the materials tested, AdheSE Bonding agent, Clearfil Protect Bond Bonding agent, and Clearfil Tri S Bond exhibited no inhibition zone (-) for all bacteria tested. Among the adhesives tested Clearafil Protect Bond Primer based upon monomer methacryloyloxydodecylpyridiniium bromide (MDPB) was found to be the most potent material against L. acidophilus and L. casei. AdheSE Primer and Adper Prompt L-Pop are highly effective against S. mutans. Compared with other adhesive systems, Clearfil Protect Bond Primer (containing MDPB) showed a high antibacterial effect against all microorganizms tested. Two-step, self-etching primer/adhesive system Clearfil Protect Bond might be a suitable choice under minimally invasive restorations. The recently developed one-step, self-etching system Clearfil Tri S Bond showed no antibacterial effect against microorgazims tested.

Neuroprotective effect of lidocaine: is there clinical potential?

PubMed Central

Leng, Tiandong; Gao, Xiuren; Dilger, James P; Lin, Jun

2016-01-01

Local anesthetic lidocaine has been shown to be protective in animal models of focal and global ischemia as well as in in vitro hypoxic models. Lidocaine has been tested in patients for its potential protective effect on postoperative cognitive dysfunction. This mini-review summarizes the laboratory and clinical evidences and discusses its clinical applications as neuroprotective agent. PMID:27186318

Monoclonal antibodies passively protect BALB/c mice against Burkholderia mallei aerosol challenge.

PubMed

Treviño, Sylvia R; Permenter, Amy R; England, Marilyn J; Parthasarathy, Narayanan; Gibbs, Paul H; Waag, David M; Chanh, Tran C

2006-03-01

Glanders is a debilitating disease with no vaccine available. Murine monoclonal antibodies were produced against Burkholderia mallei, the etiologic agent of glanders, and were shown to be effective in passively protecting mice against a lethal aerosol challenge. The antibodies appeared to target lipopolysaccharide. Humoral antibodies may be important for immune protection against B. mallei infection.

Protective effects of amifostine and cyclooxygenase-1 inhibitor against normal human epidermal keratinocyte toxicity induced by methotrexate and 5-fluorouracil.

PubMed

Maiguma, Takayoshi; Kaji, Hiroaki; Makino, Kazutaka; Teshima, Daisuke

2009-07-01

Our study aimed to find more effective protective agents against mucosa toxicity induced by methotrexate and 5-fluorouracil. We focused on the relationship between oral mucositis and keratinocyte injury and examined methotrexate and 5-fluorouracil-induced cytotoxicity in normal human epidermal keratinocyte cell lines. Cell viability and superoxide radical activity were measured based on converting WST-1 (4-[3-(4-indophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzen disulfonate) to a water-soluble formazan dye. DNA synthesis by 5-bromo-2'-deoxyuridine incorporation was measured as an indirect parameter of cell proliferation. Allopurinol and amifostine were used as the radical scavengers. l-glutamine was used as a mucosa-protective agent. A cyclooxygenase inhibitor interrupting the production of hydroxyl radicals in the arachidonic acid cascade was also examined. 5-fluorouracil and methotrexate caused cytotoxicity due to the activation of intracellular superoxide radicals specifically on normal human epidermal keratinocytes. From the electron spin resonance study, it was found that allopurinol was a superoxide radical scavenger, while amifostine was hydroxyl radical scavenger. Allopurinol showed no effect on the cytotoxicity due to 5-fluorouracil and methotrexate. The cell injury induced by methotrexate was restored by amifostine. However, the cell injury induced by 5-fluorouracil was markedly recovered by a selective cyclooxygenase-1 inhibitor compared to amifostine. It was suggested that amifostine and cyclooxygenase-1 inhibitor could be useful protective agents against methotrexate and 5-fluorouracil chemotherapeutic toxicity. Additionally, this in vitro cell injury model using normal human epidermal keratinocytes may be useful for understanding the pathophysiology of oral mucositis induced by chemotherapeutic agents.

Imprudent Gastro-protective Approach in Majority of Specialists’ Clinics of a Tertiary Hospital

PubMed Central

Patel, Hardik Rameshbhai

2016-01-01

Introduction One out of four prescriptions in out-patient departments contains a gastro-protective drug (APUD) - PPI/ H2 Blockers/ Antacids/ Ulcer Protective’s. These drugs should be prescribed only when there is a justified indication. To assess the prescriptions of gastro-protective agents for appropriateness and rationality, in a tertiary care hospital setup. Materials and Methods It was a cross-sectional observational study conducted from Aug 2013 to Dec 2013 at OPDs of a Tertiary Care Teaching Hospital, Pune. A total of 260 prescriptions containing gastro-protective agents were analysed for appropriateness and rationality. Rationality of drug use was assessed by referring to standard textbooks and guidelines. Cost difference data was analysed by Wilcoxon signed rank test using GraphPad Prism 6. Results Most common class of gastro-protective agents was Proton pump inhibitors (PPIs)-73.77% (Pantoprazole & Dexrabeprazole). Only 37.3% prescriptions had an adequate indication for these drugs {GI prophylaxis (29.6%) and Acid Peptic Disease treatment (7.7%)}. Two irrational Fixed dose combinations found in the study were PPI with prokinetic agent (n=65) and Proton Pump Inhibitor + NSAID combination (n=2). Formulation, spelling and strength errors were found with 75 prescribed drugs. Medication instructions were lacking with most of the drugs. Drug interactions with co-prescribed drugs could be anticipated in 79 cases. Injudicious use of anti-peptic ulcer agents significantly increased the cost of prescriptions (p<0.0001). Conclusion Anti-ulcer drugs are overenthusiastically prescribed by all specialties which can predispose to adverse effects, drug interactions, increased cost and even erroneous prescriptions. PMID:27134889

Thermal Inactivation of Viruses

DTIC Science & Technology

1977-10-01

thermal inactivation . 12 Bibliography 20 Table 3. Thermal inactivation of viruses in foods 25 Bibliography 31 Table 4, Agents modifying...the presence of protective agents that reduce the lethal effect of heat on the viruses at temperatures below 60 C In addition, whtn solid foods...systems but were observed j when animal inoculation was utilized. It is possible that free virus nucl’lc < acid may have been the causative agent in

Antihyperglycemic Agents Are Inversely Associated With Intracranial Aneurysm Rupture.

PubMed

Can, Anil; Castro, Victor M; Yu, Sheng; Dligach, Dmitriy; Finan, Sean; Gainer, Vivian S; Shadick, Nancy A; Savova, Guergana; Murphy, Shawn; Cai, Tianxi; Weiss, Scott T; Du, Rose

2018-01-01

Previous studies have suggested a protective effect of diabetes mellitus on aneurysmal subarachnoid hemorrhage risk. However, reports are inconsistent, and objective measures of hyperglycemia in these studies are lacking. Our aim was to investigate the association between aneurysmal subarachnoid hemorrhage and antihyperglycemic agent use and glycated hemoglobin levels. The medical records of 4701 patients with 6411 intracranial aneurysms, including 1201 prospective patients, diagnosed at the Massachusetts General Hospital and Brigham and Women's Hospital between 1990 and 2016 were reviewed and analyzed. Patients were separated into ruptured and nonruptured groups. Univariate and multivariate logistic regression analyses were performed to determine the association between aneurysmal subarachnoid hemorrhage and antihyperglycemic agents and glycated hemoglobin levels. Propensity score weighting was used to account for selection bias. In both unweighted and weighted multivariate analysis, antihyperglycemic agent use was inversely and significantly associated with ruptured aneurysms (unweighted odds ratio, 0.58; 95% confidence interval, 0.39-0.87; weighted odds ratio, 0.57; 95% confidence interval, 0.34-0.96). In contrast, glycated hemoglobin levels were not significantly associated with rupture status. Antihyperglycemic agent use rather than hyperglycemia is associated with decreased risk of aneurysmal subarachnoid hemorrhage, suggesting a possible protective effect of glucose-lowering agents in the pathogenesis of aneurysm rupture. © 2017 American Heart Association, Inc.

Saffron as an antidote or a protective agent against natural or chemical toxicities.

PubMed

Razavi, Bibi Marjan; Hosseinzadeh, Hossein

2015-05-01

Saffron (Crocus sativus) is an extensively used food additive for its color and taste. Since ancient times this plant has been introduced as a marvelous medicine throughout the world. The wide spectrum of saffron pharmacological activities is related to its major constituents including crocin, crocetin and safranal. Based on several studies, saffron and its active ingredients have been used as an antioxidant, antiinflammatory and antinociceptive, antidepressant, antitussive, anticonvulsant, memory enhancer, hypotensive and anticancer. According to the literatures, saffron has remarkable therapeutic effects. The protective effects of saffron and its main constituents in different tissues including brain, heart, liver, kidney and lung have been reported against some toxic materials either natural or chemical toxins in animal studies.In this review article, we have summarized different in vitro and animal studies in scientific databases which investigate the antidotal and protective effects of saffron and its major components against natural toxins and chemical-induced toxicities. Due to the lake of human studies, further investigations are required to ascertain the efficacy of saffron as an antidote or a protective agent in human intoxication.

Effects of Styrene-Acrylic Sizing on the Mechanical Properties of Carbon Fiber Thermoplastic Towpregs and Their Composites.

PubMed

Bowman, Sean; Jiang, Qiuran; Memon, Hafeezullah; Qiu, Yiping; Liu, Wanshuang; Wei, Yi

2018-03-01

Thermoplastic towpregs are convenient and scalable raw materials for the fabrication of continuous fiber-reinforced thermoplastic matrix composites. In this paper, the potential to employ epoxy and styrene-acrylic sizing agents was evaluated for the making of carbon fiber thermoplastic towpregs via a powder-coating method. The protective effects and thermal stability of these sizing agents were investigated by single fiber tensile test and differential scanning calorimetry (DSC) measurement. The results indicate that the epoxy sizing agent provides better protection to carbon fibers, but it cannot be used for thermoplastic towpreg processing due to its poor chemical stability at high temperature. The bending rigidity of the tows and towpregs with two styrene-acrylic sizing agents was measured by cantilever and Kawabata methods. The styrene-acrylic sized towpregs show low torque values, and are suitable for further processing, such as weaving, preforming, and winding. Finally, composite panels were fabricated directly from the towpregs by hot compression molding. Both of the composite panels show superior flexural strength (>400 MPa), flexural modulus (>63 GPa), and interlaminar shear strength (>27 MPa), indicating the applicability of these two styrene-acrylic sizing agents for carbon fiber thermoplastic towpregs.

Black and white teas as potential agents to combine with amphotericin B and protect red blood cells from amphotericin B-mediated toxicity.

PubMed

Oliveira, V M; Khalil, N M; Carraro, E

2018-02-01

Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with black tea or white tea and protective of citotoxic effect. The present study shows that white and black teas have additive effects with amphotericin B against some species Candida. In addition, the combination of white and black tea with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that white and black tea is a potential agent to combine with amphotericin for antifungal efficacy and to reduce the amphotericin dose to lessen side effects.

Mobile code security

NASA Astrophysics Data System (ADS)

Ramalingam, Srikumar

2001-11-01

A highly secure mobile agent system is very important for a mobile computing environment. The security issues in mobile agent system comprise protecting mobile hosts from malicious agents, protecting agents from other malicious agents, protecting hosts from other malicious hosts and protecting agents from malicious hosts. Using traditional security mechanisms the first three security problems can be solved. Apart from using trusted hardware, very few approaches exist to protect mobile code from malicious hosts. Some of the approaches to solve this problem are the use of trusted computing, computing with encrypted function, steganography, cryptographic traces, Seal Calculas, etc. This paper focuses on the simulation of some of these existing techniques in the designed mobile language. Some new approaches to solve malicious network problem and agent tampering problem are developed using public key encryption system and steganographic concepts. The approaches are based on encrypting and hiding the partial solutions of the mobile agents. The partial results are stored and the address of the storage is destroyed as the agent moves from one host to another host. This allows only the originator to make use of the partial results. Through these approaches some of the existing problems are solved.

Microbiological control of soil-borne phytopathogenic fungi with special emphasis on wilt-inducing Fusarium oxysporum.

PubMed

Alabouvette, Claude; Olivain, Chantal; Migheli, Quirico; Steinberg, Christian

2009-11-01

Plant diseases induced by soil-borne plant pathogens are among the most difficult to control. In the absence of effective chemical control methods, there is renewed interest in biological control based on application of populations of antagonistic micro-organisms. In addition to Pseudomonas spp. and Trichoderma spp., which are the two most widely studied groups of biological control agents, the protective strains of Fusarium oxysporum represent an original model. These protective strains of F. oxysporum can be used to control wilt induced by pathogenic strains of the same species. Exploring the mechanisms involved in the protective capability of these strains is not only necessary for their development as commercial biocontrol agents but raises many basic questions related to the determinism of pathogenicity versus biocontrol capacity in the F. oxysporum species complex. In this paper, current knowledge regarding the interaction between the plant and the protective strains is reviewed in comparison with interactions between the plant and pathogenic strains. The success of biological control depends not only on plant-microbial interactions but also on the ecological fitness of the biological control agents.

Effects of Wearing NBC (Nuclear, Biological and Chemical) Protective Clothing in the Heat on Detection of Visual Signals

DTIC Science & Technology

1985-02-01

agents, as well as nuclear weaponry. In the face of’ such threats, the United States Army has developed equinment and clothing systems designed to...AD_ REPORT NO. T7185 EFFECTS OF WEARING NBC PROTECTIVE CLOTHING IN THE HEAT ON DETECTION OF VISUAL SIGNALS U S ARMY RESEARCH INSTITUTE N OF...CATALOG NUMBER T7/•5 ( 4. TITLE (and Subtitle) 5. TYPE OF REPORT & PERIOD COVERED Effects of Wearing NBC Protective Clothing in the Technical Report Heat

Effects of Toxins on Arachidonic Acid Metabolism in Cultured Rat Pulmonary Alveolar Macrophages

DTIC Science & Technology

1988-12-28

response to’toixin exposure, and fluocinolone may protect against .T-2 toxicosis. Some natural toxins are potent a nd powerful inflammtatory agents (1,2...macrophages in the inflammatory response to natural toxins, we examined the effect of T-2, microcystin-LR known inflammatory agents, and also included...effective in inducing the release of arachidonic acid metabolites, probably due to non-inflammatory nature of the toxin. We observed a large increase in

Synthetic Cannabinoid and Mitragynine Exposure of Law Enforcement Agents During the Raid of an Illegal Laboratory - Nevada, 2014.

PubMed

Tapp, Loren; Ramsey, Jessica G; Wen, Anita; Gerona, Roy

2017-12-01

Synthetic cannabinoids (SCs), commonly known by the street name "Spice," are designer drugs of abuse that mimic the psychoactive effects of marijuana. Intentional SC use has resulted in multiple toxicities (1,2), but little is known about occupational SC exposure. After a federal agency's law enforcement personnel in Nevada reported irritability and feeling "high" after raiding illegal SC laboratories and processing seized SCs, a request for a health hazard evaluation was made by the agency to CDC's National Institute for Occupational Safety and Health (NIOSH) in 2014 to evaluate agents' occupational SC exposures. After making the request for a health hazard evaluation, federal agents conducted a raid of an illegal SC laboratory, with assistance from local law enforcement and Drug Enforcement Administration (DEA) personnel and with NIOSH investigators observing from a distance. After the raid, agents collected and processed material evidence. NIOSH investigators tested agents' urine for SC levels before and after the raid and measured SCs in the air and on surfaces after the raid. DEA determined that AB-PINACA (an SC compound) and mitragynine (a plant material with opium-like effects, also known as "kratom") were present in the illegal laboratory. AB-PINACA, its metabolites, and mitragynine were not detected in agents' urine before the raid; however, one or more of these substances was found in the urine of six of nine agents after the raid and processing of the SC evidence. AB-PINACA was detected in one surface wipe sample from the SC laboratory; none was detected in the air in the laboratory or in the offices of the law enforcement agency where the materials were processed after the raid. No policies were in place regarding work practices and use of personal protective equipment (PPE) during raids and evidence processing. To protect agents from SC exposures, NIOSH recommended that the agency require agents to wear a minimum level of PPE (e.g., protective gloves and disposable clothing) and undergo training in PPE and in handling and storing of contaminated evidence from SC laboratory raids. Showers and locker rooms also need to be provided so that agents can reduce contamination and prevent take-home exposure.

Immobilization of Iron Nanoparticles on Multi Substrates and Its Reduction Removal of Chromium (VI) from Waste Streams

EPA Science Inventory

This article describes the in-situ synthesis and immobilization of iron nanoparticles on several substrates at room temperature using NaBH4 as a reducing agent and ascorbic acid as capping agent. The method is very effective in protecting iron nanoparticles from air oxidation for...

Vidarabine, an Anti-Herpes Virus Agent, Protects Against the Development of Heart Failure With Relatively Mild Side-Effects on Cardiac Function in a Canine Model of Pacing-Induced Dilated Cardiomyopathy.

PubMed

Nakamura, Takashi; Fujita, Takayuki; Kishimura, Megumi; Suita, Kenji; Hidaka, Yuko; Cai, Wenqian; Umemura, Masanari; Yokoyama, Utako; Uechi, Masami; Ishikawa, Yoshihiro

2016-11-25

In heart failure patients, chronic hyperactivation of sympathetic signaling is known to exacerbate cardiac dysfunction. In this study, the cardioprotective effect of vidarabine, an anti-herpes virus agent, which we identified as a cardiac adenylyl cyclase inhibitor, in dogs with pacing-induced dilated cardiomyopathy (DCM) was evaluated. In addition, the adverse effects of vidarabine on basal cardiac function was compared to those of the β-blocker, carvedilol.Methods and Results:Vidarabine and carvedilol attenuated the development of pacing-induced systolic dysfunction significantly and with equal effectiveness. Both agents also inhibited the development of cardiac apoptosis and fibrosis and reduced the Na + -Ca 2+ exchanger-1 protein level in the heart. Importantly, carvedilol significantly enlarged the left ventricle and atrium; vidarabine, in contrast, did not. Vidarabine-treated dogs maintained cardiac response to β-AR stimulation better than carvedilol-treated dogs did. Vidarabine may protect against pacing-induced DCM with less suppression of basal cardiac function than carvedilol in a dog model. (Circ J 2016; 80: 2496-2505).

Dermostyx (IB1) - High efficacy and safe topical skin protectant against percutaneous toxic agents.

PubMed

Dachir, Shlomit; Barness, Izhak; Fishbine, Eliezer; Meshulam, Jacob; Sahar, Rita; Eisenkraft, Arik; Amir, Adina; Kadar, Tamar

2017-04-01

Prevention of the penetration of toxic agents through the skin is crucial for both military troops and civilian populations. We have developed a novel topical skin protectant (TSP), coded as IB1 and commercially available as Dermostyx protective solution (Rekah Pharm, Israel). The formulation afforded significant protection against chemical warfare agents such as sulfur mustard (SM) and VX (2LD50), pesticides such as parathion and irritants such as acrolein. The efficacy of the protectant was evaluated in the pig model using clinical, histological and biochemical monitoring. A single topical application prior to exposure to the toxic agents reduced significantly the size and severity of skin lesions and ameliorated or prevented systemic clinical symptoms. The barrier properties of IB1 are immediate upon application and remain effective for at least 12 h. It is absorbed into the stratum corneum of the skin and remains there until rinsing with water, yet the ingredients are not absorbed into the body. The formulation is a hydrophilic water-based solution, composed of magnesium sulfate and glycerin that are widely used in cosmetic and medicine, and was shown to be safe in preclinical and in Phase I clinical studies. The suggested mode of action is based on the unique interaction of glycerin with the stratum corneum, changing its properties to hydrophilic and on the "salting out" effect of magnesium sulfate. The expected use of the TSP is by application on exposed skin areas and sensitive skin sites (e.g. armpits, groin, waist), when necessary. A quantity of 10 ml is sufficient for one application covering approximately 20% of the body surface area. The formulation was approved for human use by the Israel Ministry of Health and a CE mark certificate in Europe has been recently issued (Class I). Dermostyx has been adopted by the IDF and first responders as a skin protectant for special needs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Advanced UV Source for Biological Agent Destruction

DTIC Science & Technology

2006-01-01

protection against chemical agents. The AUVS can be inserted into HVAC air ducts to eliminate BW agents, used to purify water, and / or used to reduce...operating costs are very low. The technology has been shown to be very effective for destroying Bacillus pumilus endospores that are significantly more...resistant to UV than anthrax spores . Up to7 orders of magnitude (7 logs) kill of B. pumilus spores have been demonstrated with the AUVS technology

Integrating adaptive behaviour in large-scale flood risk assessments: an Agent-Based Modelling approach

NASA Astrophysics Data System (ADS)

Haer, Toon; Aerts, Jeroen

2015-04-01

Between 1998 and 2009, Europe suffered over 213 major damaging floods, causing 1126 deaths, displacing around half a million people. In this period, floods caused at least 52 billion euro in insured economic losses making floods the most costly natural hazard faced in Europe. In many low-lying areas, the main strategy to cope with floods is to reduce the risk of the hazard through flood defence structures, like dikes and levees. However, it is suggested that part of the responsibility for flood protection needs to shift to households and businesses in areas at risk, and that governments and insurers can effectively stimulate the implementation of individual protective measures. However, adaptive behaviour towards flood risk reduction and the interaction between the government, insurers, and individuals has hardly been studied in large-scale flood risk assessments. In this study, an European Agent-Based Model is developed including agent representatives for the administrative stakeholders of European Member states, insurers and reinsurers markets, and individuals following complex behaviour models. The Agent-Based Modelling approach allows for an in-depth analysis of the interaction between heterogeneous autonomous agents and the resulting (non-)adaptive behaviour. Existing flood damage models are part of the European Agent-Based Model to allow for a dynamic response of both the agents and the environment to changing flood risk and protective efforts. By following an Agent-Based Modelling approach this study is a first contribution to overcome the limitations of traditional large-scale flood risk models in which the influence of individual adaptive behaviour towards flood risk reduction is often lacking.

Pyridostigmine bromide protection against acetylcholinesterase inhibition by pesticides.

PubMed

Henderson, John D; Glucksman, Gabriela; Leong, Bryan; Tigyi, Andras; Ankirskaia, Anna; Siddique, Imteaz; Lam, Helen; DePeters, Ed; Wilson, Barry W

2012-01-01

Pyridostigmine bromide (PB) has been used to protect soldiers from the toxic effects of soman, a chemical warfare agent. Recent research shows that pyridostigmine bromide protects a significant percentage of acetylcholinesterase in isolated human intercostal muscle. Findings presented here indicate that red blood cell acetylcholinesterase is similarly protected by pyridostigmine bromide from the action of diisopropyl fluorophosphate and several organophosphate pesticides including chlorpyrifos-oxon, diazinon-oxon, and paraoxon, but not malaoxon, using the bovine red blood cell as a subject. These findings suggest that pretreatment with PB may protect growers, farmworkers, first responders, and the public, in general, from the effects of selected pesticides. Copyright © 2011 Wiley Periodicals, Inc.

Enhancement of the depigmenting effect of hydroquinone and 4-hydroxyanisole by all-trans-retinoic acid (tretinoin): the impairment of glutathione-dependent cytoprotection?

PubMed

Kasraee, Behrooz; Handjani, Farhad; Aslani, Fatemeh S

2003-01-01

Many of the well-known depigmenting agents such as hydroquinone and 4-hydroxyanisole are, in fact, melanocytotoxic chemicals which are oxidized in melanocytes to produce highly toxic compounds such as quinones. These cytotoxic compounds are responsible for the destruction of pigment cells, which results in skin depigmentation. However, cells are capable of protecting themselves against cytotoxic agents by intracellular glutathione (GSH). This protection takes place under the enzymatic action of the detoxification enzyme glutathione S-transferase (GST), which is responsible for the conjugation of toxic species to GSH. The depigmenting effect of hydroquinone is shown to be potentiated by buthionine sulfoximine (BSO) and cystamine as the result of the reduction of intracellular levels of GSH by these two agents. Additionally, BSO and cystamine are shown to inhibit the activity of GST. The combination of all-trans-retinoic acid (tretinoin, TRA) with hydroquinone or 4-hydroxyanisole is also known to produce synergetic skin depigmentation. TRA serves as a potent inhibitor of mammalian GSTs and is known to make cells more susceptible to the cytotoxic effect of chemicals by inhibiting the activity of this enzyme. This agent is also shown to reduce the level of intracellular GSH in certain cells. We have proposed that the mechanism of action of TRA to synergistically enhance the melanocytotoxic effect of chemicals involves the inhibition of GST and the impairment of glutathione-dependent cytoprotection against melanocytotoxic agents. Copyright 2003 S. Karger AG, Basel

HIV prevention trial design in an era of effective pre-exposure prophylaxis.

PubMed

Cutrell, Amy; Donnell, Deborah; Dunn, David T; Glidden, David V; Grobler, Anneke; Hanscom, Brett; Stancil, Britt S; Meyer, R Daniel; Wang, Ronnie; Cuffe, Robert L

2017-01-01

Pre-exposure prophylaxis (PrEP) has demonstrated remarkable effectiveness protecting at-risk individuals from HIV-1 infection. Despite this record of effectiveness, concerns persist about the diminished protective effect observed in women compared with men and the influence of adherence and risk behaviors on effectiveness in targeted subpopulations. Furthermore, the high prophylactic efficacy of the first PrEP agent, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), presents challenges for demonstrating the efficacy of new candidates. Trials of new agents would typically require use of non-inferiority (NI) designs in which acceptable efficacy for an experimental agent is determined using pre-defined margins based on the efficacy of the proven active comparator (i.e. TDF/FTC) in placebo-controlled trials. Setting NI margins is a critical step in designing registrational studies. Under- or over-estimation of the margin can call into question the utility of the study in the registration package. The dependence on previous placebo-controlled trials introduces the same issues as external/historical controls. These issues will need to be addressed using trial design features such as re-estimated NI margins, enrichment strategies, run-in periods, crossover between study arms, and adaptive re-estimation of sample sizes. These measures and other innovations can help to ensure that new PrEP agents are made available to the public using stringent standards of evidence.

Genoprotective effect of Phyllanthus orbicularis extract against UVA, UVB and solar radiation.

PubMed

Vernhes Tamayo, Marioly; Schuch, André Passaglia; Yagura, Teiti; Baly Gil, Luis; Menck, Carlos Frederico Martins; Sánchez-Lamar, Angel

2018-05-16

One approach to protect the human skin against harmful effects of solar ultraviolet (UV) radiation is to use natural products as photoprotectors. In this work, the extract from specie Phyllanthus orbicularis K was evaluated as a protective agent against the photodamage by UVB, UVA artificial lamps and environmental sunlight exposure. The plasmid DNA solutions were exposed to radiations using the DNA-dosimeter system in presence of plant extract. The DNA repair enzymes, E. coli Formamidopyrimidine-DNA glycosylase (Fpg) and T4 bacteriophage endonuclease V (T4-endo V), were employed to discriminate oxidized DNA damage and cyclobutane pyrimidine dimers (CPD) respectively. The supercoiled and relaxed forms of DNA were separated through electrophoretic migration in agarose gels. These DNA forms were quantified to determine strands break, representing the types of lesion levels. The results showed that, in presence of P. orbicularis extract, the CPD and oxidative damage were reduced in irradiated DNA samples. The photoprotective effect of extract was more evident for UVB and sunlight radiation than for UVA. This work documents the UV absorbing properties of P. orbicularis aqueous extract and opens up new vistas in its characterization as protective agent against DNA damage induced by environmental sunlight radiation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cutaneous challenge with chemical warfare agents in the SKH-1 hairless mouse. (I) Development of a model for screening studies in skin decontamination and protection.

PubMed

Dorandeu, F; Taysse, L; Boudry, I; Foquin, A; Hérodin, F; Mathieu, J; Daulon, S; Cruz, C; Lallement, G

2011-06-01

Exposure to lethal chemical warfare agents (CWAs) is no longer only a military issue due to the terrorist threat. Among the CWAs of concern are the organophosphorus nerve agent O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX) and the vesicant sulfur mustard (SM). Although efficient means of decontamination are available, most of them lose their efficacy when decontamination is delayed after exposure of the bare skin. Alternatively, CWA skin penetration can be prevented by topical skin protectants. Active research in skin protection and decontamination is thus paramount. In vivo screening of decontaminants or skin protectants is usually time consuming and may be expensive depending on the animal species used. We were thus looking for a suitable, scientifically sound and cost-effective model, which is easy to handle. The euthymic hairless mouse Crl: SKH-1 (hr/hr) BR is widely used in some skin studies and has previously been described to be suitable for some experiments involving SM or SM analogs. To evaluate the response of this species, we studied the consequences of exposing male anaesthetized SKH-1 mice to either liquid VX or to SM, the latter being used in liquid form or as saturated vapours. Long-term effects of SM burn were also evaluated. The model was then used in the companion paper (Taysse et al.(1)).

Vaginal microbicides: detecting toxicities in vivo that paradoxically increase pathogen transmission

PubMed Central

Cone, Richard A; Hoen, Timothy; Wong, XiXi; Abusuwwa, Raed; Anderson, Deborah J; Moench, Thomas R

2006-01-01

Background Microbicides must protect against STD pathogens without causing unacceptable toxic effects. Microbicides based on nonoxynol-9 (N9) and other detergents disrupt sperm, HSV and HIV membranes, and these agents are effective contraceptives. But paradoxically N9 fails to protect women against HIV and other STD pathogens, most likely because it causes toxic effects that increase susceptibility. The mouse HSV-2 vaginal transmission model reported here: (a) Directly tests for toxic effects that increase susceptibility to HSV-2, (b) Determines in vivo whether a microbicide can protect against HSV-2 transmission without causing toxicities that increase susceptibility, and (c) Identifies those toxic effects that best correlate with the increased HSV susceptibility. Methods Susceptibility was evaluated in progestin-treated mice by delivering a low-dose viral inoculum (0.1 ID50) at various times after delivering the candidate microbicide to detect whether the candidate increased the fraction of mice infected. Ten agents were tested – five detergents: nonionic (N9), cationic (benzalkonium chloride, BZK), anionic (sodium dodecylsulfate, SDS), the pair of detergents in C31G (C14AO and C16B); one surface active agent (chlorhexidine); two non-detergents (BufferGel®, and sulfonated polystyrene, SPS); and HEC placebo gel (hydroxyethylcellulose). Toxic effects were evaluated by histology, uptake of a 'dead cell' dye, colposcopy, enumeration of vaginal macrophages, and measurement of inflammatory cytokines. Results A single dose of N9 protected against HSV-2 for a few minutes but then rapidly increased susceptibility, which reached maximum at 12 hours. When applied at the minimal concentration needed for brief partial protection, all five detergents caused a subsequent increase in susceptibility at 12 hours of ~20–30-fold. Surprisingly, colposcopy failed to detect visible signs of the N9 toxic effect that increased susceptibility at 12 hours. Toxic effects that occurred contemporaneously with increased susceptibility were rapid exfoliation and re-growth of epithelial cell layers, entry of macrophages into the vaginal lumen, and release of one or more inflammatory cytokines (Il-1β, KC, MIP 1α, RANTES). The non-detergent microbicides and HEC placebo caused no significant increase in susceptibility or toxic effects. Conclusion This mouse HSV-2 model provides a sensitive method to detect microbicide-induced toxicities that increase susceptibility to infection. In this model, there was no concentration at which detergents provided protection without significantly increasing susceptibility. PMID:16740164

Misoprostol, an anti-ulcer agent and PGE2 receptor agonist, protects against cerebral ischemia.

PubMed

Li, Jun; Liang, Xibin; Wang, Qian; Breyer, Richard M; McCullough, Louise; Andreasson, Katrin

2008-06-20

Induction of COX-2 activity in cerebral ischemia results in increased neuronal injury and infarct size. Recent studies investigating neurotoxic mechanisms of COX-2 demonstrate both toxic and paradoxically protective effects of downstream prostaglandin receptor signaling pathways. We tested whether misoprostol, a PGE(2) receptor agonist that is utilized clinically as an anti-ulcer agent and signals through the protective PGE(2) EP2, EP3, and EP4 receptors, would reduce brain injury in the murine middle cerebral artery occlusion-reperfusion (MCAO-RP) model. Administration of misoprostol, at the time of MCAO or 2h after MCAO, resulted in significant rescue of infarct volume at 24 and 72h. Immunocytochemistry demonstrated dynamic regulation of the EP2 and EP4 receptors during reperfusion in neurons and endothelial cells of cerebral cortex and striatum, with limited expression of EP3 receptor. EP3-/- mice had no significant changes in infarct volume compared to control littermates. Moreover, administration of misoprostol to EP3+/+ and EP3-/- mice showed similar levels of infarct rescue, indicating that misoprostol protection was not mediated through the EP3 receptor. Taken together, these findings suggest a novel function for misoprostol as a protective agent in cerebral ischemia acting via the PGE(2) EP2 and/or EP4 receptors.

Pseudomonas putida AlkA and AlkB Proteins Comprise Different Defense Systems for the Repair of Alkylation Damage to DNA – In Vivo, In Vitro, and In Silico Studies

PubMed Central

Mielecki, Damian; Saumaa, Signe; Wrzesiński, Michał; Maciejewska, Agnieszka M.; Żuchniewicz, Karolina; Sikora, Anna; Piwowarski, Jan; Nieminuszczy, Jadwiga; Kivisaar, Maia; Grzesiuk, Elżbieta

2013-01-01

Alkylating agents introduce cytotoxic and/or mutagenic lesions to DNA bases leading to induction of adaptive (Ada) response, a mechanism protecting cells against deleterious effects of environmental chemicals. In Escherichia coli, the Ada response involves expression of four genes: ada, alkA, alkB, and aidB. In Pseudomonas putida, the organization of Ada regulon is different, raising questions regarding regulation of Ada gene expression. The aim of the presented studies was to analyze the role of AlkA glycosylase and AlkB dioxygenase in protecting P. putida cells against damage to DNA caused by alkylating agents. The results of bioinformatic analysis, of survival and mutagenesis of methyl methanesulfonate (MMS) or N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) treated P. putida mutants in ada, alkA and alkB genes as well as assay of promoter activity revealed diverse roles of Ada, AlkA and AlkB proteins in protecting cellular DNA against alkylating agents. We found AlkA protein crucial to abolish the cytotoxic but not the mutagenic effects of alkylans since: (i) the mutation in the alkA gene was the most deleterious for MMS/MNNG treated P. putida cells, (ii) the activity of the alkA promoter was Ada-dependent and the highest among the tested genes. P. putida AlkB (PpAlkB), characterized by optimal conditions for in vitro repair of specific substrates, complementation assay, and M13/MS2 survival test, allowed to establish conservation of enzymatic function of P. putida and E. coli AlkB protein. We found that the organization of P. putida Ada regulon differs from that of E. coli. AlkA protein induced within the Ada response is crucial for protecting P. putida against cytotoxicity, whereas Ada prevents the mutagenic action of alkylating agents. In contrast to E. coli AlkB (EcAlkB), PpAlkB remains beyond the Ada regulon and is expressed constitutively. It probably creates a backup system that protects P. putida strains defective in other DNA repair systems against alkylating agents of exo- and endogenous origin. PMID:24098441

Develop Silicone Encapsulation Systems for Terrestrial Silicon Solar Arrays

NASA Technical Reports Server (NTRS)

1979-01-01

A cost effective encapsulant system was identified and a silicone acrylic cover material containing a durable ultraviolet screening agent was prepared. The effectiveness of the cover material in protecting photo-oxidatively sensitive polymers was demonstrated.

Rational Tuning of Visual Cycle Modulator Pharmacodynamics

PubMed Central

Kiser, Philip D.; Zhang, Jianye; Badiee, Mohsen; Kinoshita, Junzo; Peachey, Neal S.; Tochtrop, Gregory P.

2017-01-01

Modulators of the visual cycle have been developed for treatment of various retinal disorders. These agents were designed to inhibit retinoid isomerase [retinal pigment epithelium-specific 65 kDa protein (RPE65)], the rate-limiting enzyme of the visual cycle, based on the idea that attenuation of visual pigment regeneration could reduce formation of toxic retinal conjugates. Of these agents, certain ones that contain primary amine groups can also reversibly form retinaldehyde Schiff base adducts, which contributes to their retinal protective activity. Direct inhibition of RPE65 as a therapeutic strategy is complicated by adverse effects resulting from slowed chromophore regeneration, whereas effective retinal sequestration can require high drug doses with potential off-target effects. We hypothesized that the RPE65-emixustat crystal structure could help guide the design of retinaldehyde-sequestering agents with varying degrees of RPE65 inhibitory activity. We found that addition of an isopropyl group to the central phenyl ring of emixustat and related compounds resulted in agents effectively lacking in vitro retinoid isomerase inhibitory activity, whereas substitution of the terminal 6-membered ring with branched moieties capable of stronger RPE65 interaction potentiated inhibition. The isopropyl derivative series produced discernible visual cycle suppression in vivo, albeit much less potently than compounds with a high affinity for the RPE65 active site. These agents were distributed into the retina and formed Schiff base adducts with retinaldehyde. Except for one compound [3-amino-1-(3-isopropyl-5-((2,6,6-trimethylcyclohex-1-en-1-yl)methoxy)phenyl)propan-1-ol (MB-007)], these agents conferred protection against retinal phototoxicity, suggesting that both direct RPE65 inhibition and retinal sequestration are mechanisms of potential therapeutic relevance. PMID:28476927

Effectiveness of two systemic insecticides for protecting western conifers from mortality due to bark beetle attack

Treesearch

D.M. Grosman; C.J. Fettig; C.L. Jorgensen; A.S. Munson

2010-01-01

Bark beetles (Coleoptera: Curculionidae, Scolytinae) are important tree mortality agents in western coniferous forests. Protection of individual trees from bark beetle attack has historically involved applications of liquid formulations of contact insecticides to the tree bole using hydraulic sprayers. More recently, researchers looking for more portable and...

Protection of autonomous microgrids using agent-based distributed communication

DOE PAGES

Cintuglu, Mehmet H.; Ma, Tan; Mohammed, Osama A.

2016-04-06

This study presents a real-time implementation of autonomous microgrid protection using agent-based distributed communication. Protection of an autonomous microgrid requires special considerations compared to large scale distribution net-works due to the presence of power converters and relatively low inertia. In this work, we introduce a practical overcurrent and a frequency selectivity method to overcome conventional limitations. The proposed overcurrent scheme defines a selectivity mechanism considering the remedial action scheme (RAS) of the microgrid after a fault instant based on feeder characteristics and the location of the intelligent electronic devices (IEDs). A synchrophasor-based online frequency selectivity approach is proposed to avoidmore » pulse loading effects in low inertia microgrids. Experimental results are presented for verification of the pro-posed schemes using a laboratory based microgrid. The setup was composed of actual generation units and IEDs using IEC 61850 protocol. The experimental results were in excellent agreement with the proposed protection scheme.« less

Protection of autonomous microgrids using agent-based distributed communication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cintuglu, Mehmet H.; Ma, Tan; Mohammed, Osama A.

This study presents a real-time implementation of autonomous microgrid protection using agent-based distributed communication. Protection of an autonomous microgrid requires special considerations compared to large scale distribution net-works due to the presence of power converters and relatively low inertia. In this work, we introduce a practical overcurrent and a frequency selectivity method to overcome conventional limitations. The proposed overcurrent scheme defines a selectivity mechanism considering the remedial action scheme (RAS) of the microgrid after a fault instant based on feeder characteristics and the location of the intelligent electronic devices (IEDs). A synchrophasor-based online frequency selectivity approach is proposed to avoidmore » pulse loading effects in low inertia microgrids. Experimental results are presented for verification of the pro-posed schemes using a laboratory based microgrid. The setup was composed of actual generation units and IEDs using IEC 61850 protocol. The experimental results were in excellent agreement with the proposed protection scheme.« less

Photo Protection of Haematococcus pluvialis Algae by Astaxanthin: Unique Properties of Astaxanthin Deduced by EPR, Optical and Electrochemical Studies

PubMed Central

Focsan, A. Ligia; Polyakov, Nikolay E.; Kispert, Lowell D.

2017-01-01

The antioxidant astaxanthin is known to accumulate in Haematococcus pluvialis algae under unfavorable environmental conditions for normal cell growth. The accumulated astaxanthin functions as a protective agent against oxidative stress damage, and tolerance to excessive reactive oxygen species (ROS) is greater in astaxanthin-rich cells. The detailed mechanisms of protection have remained elusive, however, our Electron Paramagnetic Resonance (EPR), optical and electrochemical studies on carotenoids suggest that astaxanthin’s efficiency as a protective agent could be related to its ability to form chelate complexes with metals and to be esterified, its inability to aggregate in the ester form, its high oxidation potential and the ability to form proton loss neutral radicals under high illumination in the presence of metal ions. The neutral radical species formed by deprotonation of the radical cations can be very effective quenchers of the excited states of chlorophyll under high irradiation. PMID:29065482

Expression of HSP72 in the gastric mucosa is regulated by gastric acid in rats-Correlation of HSP72 expression with mucosal protection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wada, Isao; Otaka, Michiro; Jin, Mario

2006-10-20

Background and aim: The real mechanism of adaptive cytoprotection in the gastric mucosa is not well established. In the present study, we investigated the effect of acid suppressing agents on a 72-kDa heat shock protein (HSP72) expression, which is known as endogenous cytoprotective factor, in the gastric mucosa. Also, the association of gastric mucosal protective function against HCl-challenge was compared between HSP72-induced and -reduced group. Materials and methods: Expression of HSP72 was measured by Western blotting in the gastric mucosa before and after administration of famotidine or omeprazole. The gastric mucosal protective function against 0.6 N HCl was compared betweenmore » control group and HSP72-reduced group. Also, the effect of increased expression of gastric HSP72 by additional administration of zinc sulfate or zinc L-carnosine, which is known as HSP72-inducer, on mucosal protective function was studied. Results: HSP72 expression in the gastric mucosa was reduced by acid suppressing agents. The lowest expression level of HSP72 was observed 12 h (famotidine, H2-receptor antagonist) or 48 h (omeprazole, proton pump inhibitor) after administration. The gastric mucosal protective ability against 0.6 N HCl was also reduced when HSP72 expression was decreased by famotidine or omeprazole. This phenomenon was reversed by HSP72 induction by additional administration of zinc derivatives. Conclusion: Our results might indicate that the expression of HSP72 in the gastric mucosa is physiologically regulated by gastric acid, and that HSP72 induction could be important in view of mucosal protection especially when HSP72 expression is reduced by administration of acid suppressing agents such as proton pump inhibitor or H2 receptor antagonist.« less

Preparation and mechanism analysis of an environment-friendly maize seed coating agent.

PubMed

Zeng, Defang; Fan, Zhao; Tian, Xu; Wang, Wenjin; Zhou, Mingchun; Li, Haochuan

2018-06-01

Traditional seed coating agents often contain toxic ingredients, which contaminate the environment and threaten human health. This paper expounds a method of preparing a novel environment-friendly seed coating agent for maize and researches its mechanism of action. The natural polysaccharide polymer, which is the main active ingredient of this environment-friendly seed coating agent, has the characteristics of innocuity and harmlessness, and it can replace the toxic ingredients used in traditional seed coating agents. This environment-friendly seed coating agent for maize was mainly made up of the natural polysaccharide polymer and other additives. The field trials results showed that the control efficacy of Helminthosporium maydis came to 93.72%, the anti-feeding rate of cutworms came to 81.29%, and the maize yield was increased by 17.75%. Besides, the LD 50 value (half the lethal dose in rats) of this seed coating agent was 10 times higher than that of the traditional seed coating agents. This seed coating agent could improve the activity of plant protective enzymes (peroxidase, catalase and superoxidase dismutase) and increase the chlorophyll content. This seed coating agent has four characteristics of disease prevention, desinsectization, increasing yield and safety. Results of mechanism analyses showed that this seed coating agent could enhance disease control effectiveness by improving plant protective enzymes activity and increase maize yield by improving chlorophyll content. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

In Search of an Effective in vivo Reactivator for Organophosphorus Nerve Agent-Inhibited Acetylcholinesterase in the Central Nervous System

DTIC Science & Technology

2012-01-01

monoisonitrosoacetone (MINA) crossed BBB, provided some degree of CNS AChE reactivation, enhanced survival, and mitigated the seizure activity following nerve agent...tissues (brain regions, diaphragm, heart, skeletal muscle) were collected. AChE activity was measured using the Ellman assay. In GB exposure, pro...therapy. Protecting and/or restoring AChE activity in the brain is a major goal in the treatment of nerve agent intoxication. Our long-term goal is to

Burkholderia mallei CLH001 Attenuated Vaccine Strain Is Immunogenic and Protects against Acute Respiratory Glanders

PubMed Central

Hatcher, Christopher L.; Mott, Tiffany M.; Muruato, Laura A.; Sbrana, Elena

2016-01-01

Burkholderia mallei is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffective treatment options emphasize its public health threat and highlight the need for a vaccine. Live attenuated vaccines are considered the most viable vaccine strategy for Burkholderia, but single-gene-deletion mutants have not provided complete protection. In this study, we constructed the select-agent-excluded B. mallei ΔtonB Δhcp1 (CLH001) vaccine strain and investigated its ability to protect against acute respiratory glanders. Here we show that CLH001 is attenuated, safe, and effective at protecting against lethal B. mallei challenge. Intranasal administration of CLH001 to BALB/c and NOD SCID gamma (NSG) mice resulted in complete survival without detectable colonization or abnormal organ histopathology. Additionally, BALB/c mice intranasally immunized with CLH001 in a prime/boost regimen were fully protected against lethal challenge with the B. mallei lux (CSM001) wild-type strain. PMID:27271739

Anti-radiation damage effect of polyethylenimine as a toll-like receptor 5 targeted agonist

PubMed Central

Hu, Zhiqiang; Xing, Yaling; Qian, Yuanyu; Chen, Xiaojuan; Tu, Jian; Ren, Lening; Wang, Kai; Chen, Zhongbin

2013-01-01

A number of agents are now available for use in protecting against ionizing radiation. These radiation-protective agents, however, have many adverse effects. Efforts have been made to develop new radiation-protective agents for medical application. Here, we investigated whether a compound, polyethylenimine (PEI), which activates Toll-like receptor 5 (TLR5)-mediated NF-kB signaling pathways, could have an anti-radiation effect on a mouse model. First, a cell-based screening model for an agonist of TLR5-mediated NF-kB pathway was established and then validated by activation of TLR5-mediated NF-kB luciferase reporter activity with a known TLR5 agonist, flagellin. We found that PEI induced dose-dependent activation of the TLR5-mediated NF-kB pathway, indicating that PEI is indeed a TLR5 agonist. Furthermore, the anti-radiation effect of polyethylenimine was assessed using a γ-ray total body irradiation (TBI) mouse model. Compared with the irradiation control, both survival time and survival rate were significantly improved in mice that received either a low dose of polyethylenimine (P= 0.019) or a high dose of polyethylenimine (P< 0.001). We also observed a positive correlation between animal body weight and survival time in mice that received a low dose of polyethylenimine, a high dose of polyethylenimine and amifostine, over a period of 30 days, r= 0.42 (P< 0.02), 0.72 (P< 0.0001) and 0.95 (P< 0.0001), respectively, while a negative correlation between animal body weight and survival time was observed in the irradiation control (r= –0.89; P< 0.0001). These results indicate that polyethylenimine is a new TLR5 agonist with potential application in offering protection for patients receiving radiotherapy or in radiation-related accidents. PMID:23104900

Anti-radiation damage effect of polyethylenimine as a toll-like receptor 5 targeted agonist.

PubMed

Hu, Zhiqiang; Xing, Yaling; Qian, Yuanyu; Chen, Xiaojuan; Tu, Jian; Ren, Lening; Wang, Kai; Chen, Zhongbin

2013-03-01

A number of agents are now available for use in protecting against ionizing radiation. These radiation-protective agents, however, have many adverse effects. Efforts have been made to develop new radiation-protective agents for medical application. Here, we investigated whether a compound, polyethylenimine (PEI), which activates Toll-like receptor 5 (TLR5)-mediated NF-kB signaling pathways, could have an anti-radiation effect on a mouse model. First, a cell-based screening model for an agonist of TLR5-mediated NF-kB pathway was established and then validated by activation of TLR5-mediated NF-kB luciferase reporter activity with a known TLR5 agonist, flagellin. We found that PEI induced dose-dependent activation of the TLR5-mediated NF-kB pathway, indicating that PEI is indeed a TLR5 agonist. Furthermore, the anti-radiation effect of polyethylenimine was assessed using a γ-ray total body irradiation (TBI) mouse model. Compared with the irradiation control, both survival time and survival rate were significantly improved in mice that received either a low dose of polyethylenimine (P= 0.019) or a high dose of polyethylenimine (P< 0.001). We also observed a positive correlation between animal body weight and survival time in mice that received a low dose of polyethylenimine, a high dose of polyethylenimine and amifostine, over a period of 30 days, r= 0.42 (P< 0.02), 0.72 (P< 0.0001) and 0.95 (P< 0.0001), respectively, while a negative correlation between animal body weight and survival time was observed in the irradiation control (r= -0.89; P< 0.0001). These results indicate that polyethylenimine is a new TLR5 agonist with potential application in offering protection for patients receiving radiotherapy or in radiation-related accidents.

Preventive effects of different protective agents on dentin erosion: An in vitro investigation

PubMed Central

Gulino, Chiara; Mirando, Maria; Colombo, Marco; Pietrocola, Giampiero

2017-01-01

Background The purpose of this in vitro study was to evaluate the preventive effects of different protective agents on dentine erosion, measuring mean percentage weight loss. Dissolution of dentine under erosive challenges caused by soft drinks was analyzed: specimens were weighed following each immersion period, with mean percent weight losses calculated. Material and Methods Extracted teeth were sectioned into uniform slabs. Seventy permanent enamel specimens were randomly distributed to seven groups. Initial weights of all dentin specimens were performed. The fluoride pastes Remin Pro, MI Paste Plus, Tooth Mousse, Biorepair, Biorepair Plus and Regenerate were used in this study. A control group was treated just with tap water. The specimens then were immersed in Coca-Cola for a total of 32 min at room temperature. Finally each specimen was dry and weighed. The mass loss was calculated as a percentage of that observed prior the fluoride pastes application. Weight loss data were subjected to Analysis of Variance (One-way ANOVA) followed by Bonferroni’s post hoc tests. Results Percent weight loss of specimens exposed to early stages in Coca-Cola showed linear progression with time. Specimen’s application of fluoridated varnishes such as Biorepair or Regenerate, prior immersion in Coca-Cola, significantly protect dentin from demineralization. Otherwise, application of Tooth Mousse or Biorepair Plus increased dentin demineralization starting from 24 min of immersion in Coca-Cola. Conclusions Despite the limitations of this study, the protective pastes that showed the less weight loss due to the acidic challenge are Biorepair and Regenerate. Key words:Dentine, erosion, protective agents, soft drinks, toothpastes. PMID:28149456

Preventive effects of different protective agents on dentin erosion: An in vitro investigation.

PubMed

Poggio, Claudio; Gulino, Chiara; Mirando, Maria; Colombo, Marco; Pietrocola, Giampiero

2017-01-01

The purpose of this in vitro study was to evaluate the preventive effects of different protective agents on dentine erosion, measuring mean percentage weight loss. Dissolution of dentine under erosive challenges caused by soft drinks was analyzed: specimens were weighed following each immersion period, with mean percent weight losses calculated. Extracted teeth were sectioned into uniform slabs. Seventy permanent enamel specimens were randomly distributed to seven groups. Initial weights of all dentin specimens were performed. The fluoride pastes Remin Pro, MI Paste Plus, Tooth Mousse, Biorepair, Biorepair Plus and Regenerate were used in this study. A control group was treated just with tap water. The specimens then were immersed in Coca-Cola for a total of 32 min at room temperature. Finally each specimen was dry and weighed. The mass loss was calculated as a percentage of that observed prior the fluoride pastes application. Weight loss data were subjected to Analysis of Variance (One-way ANOVA) followed by Bonferroni's post hoc tests. Percent weight loss of specimens exposed to early stages in Coca-Cola showed linear progression with time. Specimen's application of fluoridated varnishes such as Biorepair or Regenerate, prior immersion in Coca-Cola, significantly protect dentin from demineralization. Otherwise, application of Tooth Mousse or Biorepair Plus increased dentin demineralization starting from 24 min of immersion in Coca-Cola. Despite the limitations of this study, the protective pastes that showed the less weight loss due to the acidic challenge are Biorepair and Regenerate. Key words: Dentine, erosion, protective agents, soft drinks, toothpastes.

NAD+ and SIRT3 control microtubule dynamics and reduce susceptibility to antimicrotubule agents

PubMed Central

Harkcom, William T.; Ghosh, Ananda K.; Sung, Matthew S.; Matov, Alexandre; Brown, Kevin D.; Giannakakou, Paraskevi; Jaffrey, Samie R.

2014-01-01

Nicotinamide adenine dinucleotide (NAD+) is an endogenous enzyme cofactor and cosubstrate that has effects on diverse cellular and physiologic processes, including reactive oxygen species generation, mitochondrial function, apoptosis, and axonal degeneration. A major goal is to identify the NAD+-regulated cellular pathways that may mediate these effects. Here we show that the dynamic assembly and disassembly of microtubules is markedly altered by NAD+. Furthermore, we show that the disassembly of microtubule polymers elicited by microtubule depolymerizing agents is blocked by increasing intracellular NAD+ levels. We find that these effects of NAD+ are mediated by the activation of the mitochondrial sirtuin sirtuin-3 (SIRT3). Overexpression of SIRT3 prevents microtubule disassembly and apoptosis elicited by antimicrotubule agents and knockdown of SIRT3 prevents the protective effects of NAD+ on microtubule polymers. Taken together, these data demonstrate that NAD+ and SIRT3 regulate microtubule polymerization and the efficacy of antimicrotubule agents. PMID:24889606

Status of arenavirus vaccines and their application

PubMed Central

Johnson, Karl M.

1975-01-01

A limited but definite need exists for vaccines against Lassa, Junin, and Machupo viruses. Medical and laboratory personnel, as well as defined high-risk population groups, require protection from these highly virulent agents. To date little work has been done on inactivated vaccines for these viruses. A live attenuated Junin vaccine has been tested successfully in more than 600 persons, and a high-passage Machupo virus strain has protected rhesus monkeys against lethal infection produced by a homologous field strain. Work has been initiated on possible heterologous protection induced by infection or antigenic stimulation with arenaviruses not pathogenic for man. Crucial for the eventual development of effective vaccines are the construction of more maximum security laboratories and the further elucidation of the experimental and natural biology of the agents in lower animals and man. PMID:182407

Metabolomic Analysis of N-acetylcysteine Protection of Injury from Gadolinium-DTPA Contrast Agent in Rats with Chronic Renal Failure.

PubMed

Wan, Chuanling; Xue, Rong; Zhan, Youyang; Wu, Yijie; Li, Xiaojing; Pei, Fengkui

2017-09-01

Gadolinium-based contrast agents (GBCAs) are frequently used to enhance the diagnostic efficacy of magnetic resonance imaging. On the other hand, the association between GBCA administration in patients with advanced renal disease and nephrogenic systemic fibrosis (NSF) was also noted. NSF is a systemic disorder characterized by widespread tissue fibrosis that may lead to death. N-acetylcysteine (NAC) protects rats from injury induced by gadolinium-based contrast agents, but the underlying mechanisms remain unclear. In this study, a nuclear magnetic resonance-based metabolomic approach was used to systematically investigate the protective effects of NAC on Gd-DTPA-induced injury. Thirty-two male Sprague-Dawley rats were given adenine (200 mg·kg -1 body weight) by oral gavage once a day for 3 weeks to induce chronic renal failure (CRF). NAC (600 mg/L in drinking water for 9 days) pretreatment was initiated 2 days before Gd-DTPA injection (a single tail vein injection, 2 mmol/kg body weight). Serum and liver samples were collected on day 7 after Gd-DTPA injection. By study design, the serum and hepatic metabolic changes of rats were measured in four groups of eight each: CRF, CRF-Gd, CRF-Gd-NAC, and CRF-NAC. Gd-DTPA administration to rats with CRF resulted in disturbances of several metabolic pathways, including glucose, lipid, glutamate, choline, gut microbiota, one-carbon, and purine metabolism. NAC pretreatment reversed the abundance changes of high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, glutamate, glutamine, oxidized glutathione, choline, phosphocholine, glycerophosphocholine, trimethylamine, and trimethylamine-N-oxide induced by Gd-DTPA. It is noteworthy, however, that the ameliorating effects of NAC on the disturbance of glutamate, choline, and gut microbiota metabolism may be specific to Gd-DTPA. In all, these findings could be potentially useful to decipher the underlying mechanisms of NAC protective effects from the injury induced by gadolinium-based contrast agents.

Methodological assessment of the reduction of the content of impurities in nimodipine emulsion via the use of 21 amino acid protection

PubMed Central

Xie, Yiqiao; Zhuang, Zhiquan; Zhang, Shu; Xia, Zihua; Chen, De; Fan, Kaiyan; Ren, Jialin; Lin, CuiCui; Chen, Yanzhong; Yang, Fan

2017-01-01

Purpose The present study examined the factors affecting the content of impurities of nimodipine (NMP) emulsion and the associated methods of compound protection. Methods Destructive testing of NMP emulsion and its active pharmaceutical ingredient (API) were conducted, and ultracentrifugation was used to study the content of impurities in two phases. The impurity of NMP was measured under different potential of hydrogen (pH) conditions, antioxidants and pH-adjusting agents. Results Following destruction, the degradation of NMP notably occurred in the basic environment. The consumption of the pH-adjusting agent NaOH was proportional to the production of impurities since the inorganic base and/or acid promoted the degradation of NMP. The organic antioxidants, notably amino acids with an appropriate length of intermediate chain and electron-donating side group, exhibited improved antioxidant effects compared with inorganic antioxidants. The minimal amount of impurities was produced following addition of 0.04% lysine and 0.06% leucine in the aqueous phase and adjustment of the pH to a range of 7.5–8.0 in the presence of acetic acid solution. Conclusion NMP was more prone to degradation in an oxidative environment, in an aqueous phase and/or in the presence of inorganic pH-adjusting agents and antioxidants. The appropriate antioxidant and pH-adjusting agent should be selected according to the chemical structure, while destructive testing of the drug is considered to play the optimal protective effect. PMID:28490879

Combined cardioprotectant and antithrombotic actions of platelet P2Y12 receptor antagonists in acute coronary syndrome: just what the doctor ordered.

PubMed

Cohen, Michael V; Downey, James M

2014-03-01

Since the P2Y12 receptor antagonists were first introduced, they have been extensively tested in patients with acute coronary syndrome and are now standard of care. These antiplatelet drugs are very effective in reducing subsequent cardiovascular events, stent thromboses, and mortality in patients with acute myocardial infarction undergoing reperfusion therapy. Although the prevailing view is that their benefit derives from their antithrombotic properties, other unrelated pleiotropic effects appear to be equally beneficial. Accumulating clinical and animal evidence indicates that, if present at the time of reperfusion, these drugs have a direct anti-infarct effect similar to that of ischemic postconditioning. Four oral antagonists have been developed in rapid succession: ticlopidine, clopidogrel, prasugrel, and ticagrelor. Each agent had a more consistent and rapid onset of action than the previous one, and this has correlated with improved clinical outcomes when given early in treatment. Unfortunately, gut absorption causes an appreciable delay in the onset of effect, especially when morphine is used, and the constant push to minimize the door-to-balloon time has made it difficult to achieve adequate platelet inhibition at the time of percutaneous coronary intervention with an oral agent. An intravenous P2Y12 antagonist such as cangrelor may optimize treatment because it produces nearly maximal inhibition of platelet aggregation within minutes. If antiplatelet agents do protect through postconditioning's mechanism, then they would render any other intervention that protects through that mechanism redundant. Indeed, animals treated with cangrelor cannot be further protected by pre- or postconditioning. However, interventions that use a different mechanism such as mild hypothermia or cariporide, a Na(+)-H(+) exchange blocker, do add to cangrelor's protection. Future research should be directed toward identifying interventions that can augment the protection from antiplatelet therapy and finding a way to optimize P2Y12 inhibition at reperfusion in all patients.

STUDY ON THE CHEMICAL PROTECTION AGAINST RADIATION INJURIES. II. EFFECT OF VITAMINS B$sub 2$, B$sub 6$, H, C AND PANTOTHENIC ACID

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hashimoto, T.

Pure-bred mice were irradiated with a single exposure of 800 r (lethal dose) and 680 r (LD/sub 5//sub 0/) of x rays. No protective effect of vit. B/ sub 2/, B/sub 6/, or pantothenic acid against radiation injury was recognized. Only vit. B/sub 1/ was effective. These 2 results indicate that the protective effect of vit. B/sub 1/ is due to activation of SH base. Neither pantothenic acid nor pantothein had any radiation-protective effect, but the combined use of pantothenic acid with beta -mercaptoethylamine was effective. Probably the protection is due to some mechanism other than the SH group. Vit.more » H gave no protection, and there was some relationship between the dosage of vit. H and its toxity. Vit. C gave some protection against radiation injury, believed to be due to cooperation with glutathione in the oxidation-reduction system. This mechanism seems to be different from that of other types of radiation-protective agents. (Abstr. Japan Med., 1: No. 8, 1961)« less

Effect of certain psychopharmacological preparations on adaptation under stress conditions

NASA Technical Reports Server (NTRS)

Stanishevskaya, A. V.; Mezentseva, L. N.

1980-01-01

Experiments staged on rats demonstrated that the formation of pathological states caused by stress and accompanied by the development of ulcerative lesion of the gastric mucosa are associated with the degree of the catecholamines level drop in the mesencephalon and hypothalamus. The application of seduxen and also of combinations consisting of L-DOPA with seduxen, or with an L-adrenoblocking agent pyroxan tends to reduce the frequency of developing alcerative lesions of the stomach. The protective effect produced by the combination of L-DOPA with an L-adrenoblocking agent pyroxan is barred by an additional administration of an B-adrenoblocking agent, inderal.

The potential of tetrandrine as a protective agent for ischemic stroke.

PubMed

Chen, Yun; Tsai, Ya-Hui; Tseng, Sheng-Hong

2011-09-16

Stroke is one of the leading causes of mortality, with a high incidence of severe morbidity in survivors. The treatment to minimize tissue injury after stroke is still unsatisfactory and it is mandatory to develop effective treatment strategies for stroke. The pathophysiology of ischemic stroke is complex and involves many processes including energy failure, loss of ion homeostasis, increased intracellular calcium level, platelet aggregation, production of reactive oxygen species, disruption of blood brain barrier, and inflammation and leukocyte infiltration, etc. Tetrandrine, a bisbenzylisoquinoline alkaloid, has many pharmacologic effects including anti-inflammatory and cytoprotective effects. In addition, tetrandrine has been found to protect the liver, heart, small bowel and brain from ischemia/reperfusion injury. It is a calcium channel blocker, and can inhibit lipid peroxidation, reduce generation of reactive oxygen species, suppress the production of cytokines and inflammatory mediators, inhibit neutrophil recruitment and platelet aggregation, which are all devastating factors during ischemia/reperfusion injury of the brain. Because tetrandrine can counteract these important pathophysiological processes of ischemic stroke, it has the potential to be a protective agent for ischemic stroke.

Joint Chemical Agent Detector (JCAD): the future of chemical agent detection

NASA Astrophysics Data System (ADS)

Laljer, Charles E.; Owen, Jeffery L.

2002-06-01

The Joint Chemical Agent Detector (JCAD) will provide state of the art chemical warfare agent detection capability to ground vehicle operators. Intelligence sources estimate that over twenty counties have active chemical weapons programs. The spread of chemical weapons to third world nations, coupled with the potential for US involvement in these areas in an operational or support capacity, increases the probability that the Joint Services may encounter chemical agents and toxic industrial materials anywhere in the world. Currently, fielded chemical agent detectors are bulky, labor intensive, and subject to false readings. No legacy detector is sensitive enough to provide detection and warning of the low dose hazards associated with miosis contamination. The JCAD will provide a small, lightweight chemical agent detector for vehicle interiors, aircraft, individual personnel, shipboard, and fixed site locations. The system provides a common detection components across multi-service platforms. This common detector system will allow the Joint Services to use the same operational and support concept for more efficient utilization of resources. The JCAD will detect, identify, quantify, and warn of the presence of chemical agents prior to onset of miosis. Upon detection of chemical agents, the detector will provide local and remote audible and visual alarms to the operators. Advance warning will provide the vehicle crew with the time necessary to protect themselves from the lethal effects of chemical agents. The JCAD will also be capable of being upgraded to protect against future chemical agent threats. The JCAD will provide the vehicle operators with the warning necessary to survive and fight in a chemical warfare agent threat environment.

Infection in systemic lupus erythematosus: friend or foe?

PubMed Central

Francis, Lisa; Perl, Andras

2010-01-01

Infectious agents have long been implicated in the pathogenesis of systemic lupus erythematosus. Common viruses, such as the Epstein-Barr virus, transfusion transmitted virus, parvovirus and cytomegalovirus, have an increased prevalence in patients with systemic lupus erythematosus. They may contribute to disease pathogenesis through triggering autoimmunity via structural or functional molecular mimicry, encoding proteins that induce cross-reactive immune responses to self antigens or modulate antigen processing, activation, or apoptosis of B and T cells, macrophages or dendritic cells. Alternatively, some infectious agents, such as malaria, Toxoplasma gondii and Helicobacter pylori, may have a protective effect. Vaccinations may play dual roles by protecting against friend and foe alike. PMID:20209114

Protective Effect of a Mitochondria-Targeted Peptide against the Development of Chemotherapy-Induced Peripheral Neuropathy in Mice.

PubMed

Toyama, Satoshi; Shimoyama, Naohito; Szeto, Hazel H; Schiller, Peter W; Shimoyama, Megumi

2018-04-18

Several chemotherapeutic agents used for cancer treatment induce dose-limiting peripheral neuropathy that compromises patients' quality of life and limits cancer treatment. Recently, mitochondrial dysfunction has been shown to be involved in the mechanism of chemotherapy-induced peripheral neuropathy. SS-20 is a mitochondria-targeted peptide that promotes mitochondrial respiration and restores mitochondrial bioenergetics. In the present study, we examined the protective effect of SS-20 against the development of chemotherapy-induced peripheral neuropathy utilizing a murine model of peripheral neuropathy induced by oxaliplatin, a first-line chemotherapy agent for colon cancer. Weekly administrations of oxaliplatin induced peripheral neuropathy as demonstrated by the development of neuropathic pain and loss of intraepidermal nerve fibers in the hind paw. Continuous administration of SS-20 protected against the development of oxaliplatin-induced neuropathic pain and mitigated the loss of intraepidermal nerve fibers to normal levels. Our findings suggest that SS-20 may be a drug candidate for the prevention of chemotherapy-induced peripheral neuropathy.

The U. S. Environmental Protection Agency's inhalation RfD methodology: Risk assessment for air toxics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarabek, A.M.; Menache, M.G.; Overton, J.H. Jr.

1990-10-01

The U.S. Environmental Protection Agency (U.S. EPA) has advocated the establishment of general and scientific guidelines for the evaluation of toxicological data and their use in deriving benchmark values to protect exposed populations from adverse health effects. The Agency's reference dose (RfD) methodology for deriving benchmark values for noncancer toxicity originally addressed risk assessment of oral exposures. This paper presents a brief background on the development of the inhalation reference dose (RfDi) methodology, including concepts and issues related to addressing the dynamics of the respiratory system as the portal of entry. Different dosimetric adjustments are described that were incorporated intomore » the methodology to account for the nature of the inhaled agent (particle or gas) and the site of the observed toxic effects (respiratory or extra-respiratory). Impacts of these adjustments on the extrapolation of toxicity data of inhaled agents for human health risk assessment and future research directions are also discussed.« less

U. S. Environmental Protection Agency's inhalation RFD methodology: Risk assessment for air toxics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarabek, A.M.; Menache, M.G.; Overton, J.H.

1989-01-01

The U.S. Environmental Protection Agency (U.S. EPA) has advocated the establishment of general and scientific guidelines for the evaluation of toxicological data and their use in deriving benchmark values to protect exposed populations from adverse health effects. The Agency's reference dose (RfD) methodology for deriving benchmark values for noncancer toxicity originally addressed risk assessment of oral exposures. The paper presents a brief background on the development of the inhalation reference dose (RFDi) methodology, including concepts and issues related to addressing the dynamics of the respiratory system as the portal of entry. Different dosimetric adjustments are described that were incorporated intomore » the methodology to account for the nature of the inhaled agent (particle or gas) and the site of the observed toxic effects (respiratory or extrarespiratory). Impacts of these adjustments on the extrapolation of toxicity data of inhaled agents for human health risk assessment and future research directions are also discussed.« less

Class effect of pharmacotherapy in bipolar disorder: fact or misbelief?

PubMed Central

2011-01-01

Background Anecdotal reports suggests that most clinicians treat medications as belonging to a class with regard to all therapeutic indications; this means that the whole 'class' of drugs is considered to possesses a specific therapeutic action. The present article explores the possible existence of a true 'class effect' for agents available for the treatment of bipolar disorder. Methods We reviewed the available treatment data from randomized controlled trials (RCTs) and explored 16 'agent class'/'treatment issue' cases for bipolar disorder. Four classes of agents were examined: first-generation antipsychotics (FGAs), second-generation antipsychotics (SGAs), antiepileptics and antidepressants, with respect to their efficacy on four treatment issues of bipolar disorder (BD) (acute mania, acute bipolar depression, maintenance against mania, maintenance against depression). Results From the 16 'agent class'/' treatment issue' cases, only 3 possible class effects were detected, and they all concerned acute mania and antipsychotics. Four effect cases have not been adequately studied (FGAs against acute bipolar depression and in maintenance protection from depression, and antidepressants against acute mania and protection from mania) and they all concern treatment cases with a high risk of switching to the opposite pole, thus research in these areas is poor. There is no 'class effect' at all concerning antiepileptics. Conclusions The available data suggest that a 'class effect' is the exception rather than the rule in the treatment of BD. However, the possible presence of a 'class effect' concept discourages clinicians from continued scientific training and reading. Focused educational intervention might be necessary to change this attitude. PMID:21435226

Vaccines against biologic agents: uses and developments.

PubMed

Ales, Noel C; Katial, Rohit K

2004-03-01

Although the Geneva protocol that prohibits the use of chemical and biologic weapons was ratified in 1925, many countries failed to accept this protocol: others stipulated retaliation, and some, like the United States, did not ratify the protocol for decades. This delay allowed the continued development of chemical and biologic agents. Members of the health care community are responsible for determining the best way to protect society from the potentially devastating effects of these biologic agents. Ideally,these diseases would be prevented from ever developing into systemic illnesses. In the past, vaccination has been a successful means of eradicating disease. Vaccines remain a hopeful therapy for the future, but time is short,and there are many obstacles.Information regarding bioterrorism agents and their treatments comes mainly from dated data or from in vitro or animal studies that may not apply to human treatment and disease. Additionally, the current threat of bioterrorism does not allow enough time for accurate, well-designed,controlled studies in humans before the release of investigational vaccines. Furthermore, some human studies would not be safe or ethical. Finally,many members of society suffer from illnesses that would put them at high risk to receive prophylactic vaccination. It is therefore naive to believe that vaccines would be the ultimate protection from these agents. In addition to vaccine development, there must be concurrent investigations into disease management and treatment. Even in instances in which vaccination is known to be an effective means of disease protection. biologic agents may be presented in a manner that renders vaccines ineffective. Virulent strains of organisms may be used, more than one organism may be used in tandem to increase virulence, and strains may be selected for antibiotic and vaccine resistance. Genetically engineered strains may use virulence factors other than those targeted in vaccines, and high concentrations of organisms may overcome vaccine protection. Finally,exposure may not be immediately noted until it is too late to vaccinate, as was the case with anthrax. Even in a case, such as smallpox, in which postexposure vaccination is possible, patients will still develop disease, and the health care system may be overwhelmed. The United States government has been defensively planning and researching the use of vaccines and chemoprophylaxis against any potential biologic agents since at least 1953, and resources are still lacking. There are inadequate stockpiles of vaccine to protect the entire population. The pharmaceutical industry also lacks a means of mass producing vaccines ina short timeframe. There is no policy in place for the use of vaccines that are yet unlicensed and experimental but may be the only therapy in the event ofa terrorist attack. Investigations into these solutions have been instituted only after the September 11, 2001, attacks heightened the awareness of terrorism. Although vaccination is an effective means of prophylaxis and a means of terminating epidemics or treating active disease, there is also resistance from the general public. In some instances there is a lack of acceptance of vaccines, or the risk of side effects is too great. In other cases, a questionable benefit does not justify the expense of mass vaccination. Because of this uncertainty, mass vaccination is deemed an impractical solution to the threat of bioterrorism. Extending vaccination with most vaccines to include all members of society who may be first responders in the event of an attack should be considered. In all instances, the benefit-to-risk must be weighed ratio when deciding how and when to offer preemptive prophylaxis to protect society from a real but unknown threat.

Modulation of inflammation by vasoactive intestinal peptide and bombesin: lack of effects on neutrophil apoptosis.

PubMed

Djanani, Angela M; Kähler, Ch M

2002-01-01

Inhibition of neutrophil apoptosis has been identified as a prominent feature in chronic inflammation, parenchymal damage, and unresolved organ dysfunction. Lung injury animal models suggest that the neuropeptides vasoactive intestinal peptide and bombesin are protective. Therefore, in vitro effects of VIP and bombesin on apoptosis of normal human neutrophils were tested. For measuring effects on cell survival and apoptosis, trypan dye exclusion, colorimetric MTT assay to assess cell survival, and caspase-3 assay and annexin-V binding for analysing apoptosis rates were used. Foetal calf serum, Fas ligand, and tumour necrosis factor-alpha served as modulatory control agents; survival-promoting and apoptosis-inducing activities of the respective agents were confirmed. Vasoactive intestinal peptide and bombesin, however, failed to significantly affect cell death in neutrophils. Data suggest that direct regulation of neutrophil apoptosis is unlikely to be among the mechanisms of lung-protective actions of VIP and bombesin.

Environmental factors affect the activity of biocontrol agents against ochratoxigenic Aspergillus carbonarius on wine grape.

PubMed

De Curtis, F; de Felice, D V; Ianiri, G; De Cicco, V; Castoria, R

2012-09-17

The influence of temperature and relative humidity (RH) on the activity of three biocontrol agents-the yeast Metschnikowia pulcherrima LS16 and two strains of the yeast-like fungus Aureobasidium pullulans LS30 and AU34-2-against infection by A. carbonarius and ochratoxin A (OTA) accumulation in wine grape berries was investigated in lab-scale experiments. The presence of wounds on grape skin dramatically favored infection of berries by A. carbonarius strain A1102, since unwounded berries showed very low levels of infection at all conditions of RH and temperature tested. Artificially wounded berries pre-treated with the biocontrol agents were inoculated with the ochratoxigenic A. carbonarius strain A1102 and were incubated for 5 days at two levels of RH (60% and 100%) and three different temperatures (20, 25 and 30 °C). The three biocontrol agents were able to prevent infections at 60% RH and 20 °C. At 60% RH and 25 °C only strain AU34-2 achieved some protection on day 5, whereas at 30 °C a limited biocontrol efficacy was evident only up to day 2. At 100% RH, LS16, LS30 and AU34-2 showed effective protection of grape berries at 20 °C until the 5th day of incubation. The three biocontrol agents achieved significant protection at higher temperatures only until the 2nd day after the beginning of the experiment: all three strains at 25 °C, and only strain LS16 at 30 °C. After 5 days, the three biocontrol agents were able to significantly reduce the level of OTA in berries at all the conditions tested. This occurred even when protection from infection was not significant, except at 30 °C and 100% of RH for all the three strains, and at 25 °C and 100% of RH for strain LS16. The biocontrol agents displayed a higher rate of colonization on grape berries at 20 and 25 °C than at 30 °C. The higher value of RH (100%) appeared to increase the rate of colonization, in particular at 20 and 25 °C. Taken together, our results emphasize the significant influence of environmental factors on the effectiveness of biocontrol against A. carbonarius as well as on OTA contamination in wine grape berries, and the need for biocontrol agents that can cope with the environmental conditions that are conducive to attack by A. carbonarius. Copyright © 2012 Elsevier B.V. All rights reserved.

Deceptive Tactics for Protecting Cities Against Vehicle Borne Improvised Explosive Devices

DTIC Science & Technology

2008-03-01

burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instruction, searching...INTENTIONALLY LEFT BLANK xiii LIST OF ABBREVIATIONS ABS Agent Based Simulation ANA Agent Network Attack DVF Detection Value Function GIS Geographic...any other behavior (than perceptive) may be advantageous to the attacker. - A communicative behavior proves particularly effective over time for the

Swedish Defence Research Abstracts 1982/83-4 (Froe Foersvars Forsknings Referat 1982/83-4).

DTIC Science & Technology

1984-02-01

Proceedings of the International Symposium on protection against chemical var- fare agents (154) lhysiological tqstinS and vulnerable space for two...C3 ftroceedin* of the lntermatiftal lqosivm on protection against chemical mr fore, agents (in noglish) Per-Gummar Jassem, Nart Persons, Johe m...Symposium on protection against chemical warfare agents , which took place in Stockhols, 6-9 June 1983. The papers were presented daring sessions entitled

The Atypical Antipsychotic Agent, Clozapine, Protects Against Corticosterone-Induced Death of PC12 Cells by Regulating the Akt/FoxO3a Signaling Pathway.

PubMed

Zeng, Zhiwen; Wang, Xue; Bhardwaj, Sanjeev K; Zhou, Xuanhe; Little, Peter J; Quirion, Remi; Srivastava, Lalit K; Zheng, Wenhua

2017-07-01

Schizophrenia is one of the most severe psychiatric disorders. Increasing evidence implicates that neurodegeneration is a component of schizophrenia pathology and some atypical antipsychotics are neuroprotective and successful in slowing the progressive morphological brain changes. As an antipsychotic agent, clozapine has superior and unique effects, but the intracellular signaling pathways that mediate clozapine action remain to be elucidated. The phosphatidylinositol-3-kinase/protein kinase B/Forkhead box O3 (PI3K/Akt/FoxO3a) pathway is crucial for neuronal survival. However, little information is available regarding this pathway with clozapine. In the present study, we investigated the protective effect of clozapine on the PC12 cells against corticosterone toxicity. Our results showed that corticosterone decreases the phosphorylation of Akt and FoxO3a, leading to the nuclear localization of FoxO3a and the apoptosis of PC12 cells, while clozapine concentration dependently protected PC12 cells against corticosterone insult. Pathway inhibitors studies displayed that the protective effect of clozapine was reversed by LY294002 and wortmannin, two PI3K inhibitors, or Akt inhibitor VIII although several other inhibitors had no effect. The shRNA knockdown results displayed that downregulated Akt1 or FoxO3a attenuated the protective effect of clozapine. Western blot analyses revealed that clozapine induced the phosphorylation of Akt and FoxO3a by the PI3K/Akt pathway and reversed the reduction of the phosphorylated Akt and FoxO3a and the nuclear translocation of FoxO3a evoked by corticosterone. Together, our data indicates that clozapine protects PC12 cells against corticosterone-induced cell death by modulating activity of the PI3K/Akt/FoxO3a pathway.

Pentadecapeptide BPC 157 interactions with adrenergic and dopaminergic systems in mucosal protection in stress.

PubMed

Sikirić, P; Mazul, B; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Jurina, L; Konjevoda, P; Hanzevacki, M; Gjurasin, M; Separović, J; Ljubanović, D; Artuković, B; Bratulić, M; Tisljar, M; Miklić, P; Sumajstorcić, J

1997-03-01

Since superior protection against different gastrointestinal and liver lesions and antiinflammatory and analgesic activities were noted for pentadecapeptide BPC (an essential fragment of an organoprotective gastric juice protein named BPC), the beneficial mechanism of BPC 157 and its likely interactions with other systems were studied. Hence its beneficial effects would be abolished by adrenal gland medullectomy, the influence of different agents affecting alpha, beta, and dopamine receptors on BPC 157 gastroprotection in 48 h restraint stress was further investigated. Animals were pretreated (1 hr before stress) with saline (controls) or BPC 157 (dissolved in saline) (10 microg or 10 ng/kg body wt intraperitoneally or intragastrically) applied either alone to establish basal conditions or, when manipulating the adrenergic or dopaminergic system, a simultaneous administration was carried out with various agents with specific effects on adrenergic or dopaminergic receptors [given in milligrams per kilogram intraperitoneally except for atenolol, which was given subcutaneously] phentolamine (10.0), prazosin (0.5), yohimbine (5.0), clonidine (0.1) (alpha-adrenergic domain), propranolol (1.0), atenolol (20.0) (beta-adrenergic domain), domperidone (5.0), and haloperidol (5.0) (peripheral/central dopamine system). Alternatively, agents stimulating adrenergic or dopaminergic systems--adrenaline (5.0) or bromocriptine (10.0)--were applied. A strong protection, noted following intragastric or intraperitoneal administration of BPC 157, was fully abolished by coadministration of phentolamine, clonidine, and haloperidol, and consistently not affected by prazosin, yohimbine, or domperidone. Atenolol abolished only intraperitoneal BPC 157 protection, whereas propranolol affected specifically intragastric BPC 157 protection. Interestingly, the severe course of lesion development obtained in basal conditions, unlike BPC 157 gastroprotection, was not influenced by the application of these agents. In other experiments, when adrenaline and bromocriptine were given simultaneously, a strong reduction of lesion development was noted. However, when applied separately, only adrenaline, not bromocriptine, has a protective effect. Thus, a complex protective interaction with both alpha-adrenergic (eg, catecholamine release) and dopaminergic (central) systems could be suggested for both intragastric and intraperitoneal BPC 157 administration. The involvement of beta-receptor stimulation in BPC 157 gastroprotection appears to be related to the route of BPC 157 administration. The demonstration that a combined stimulation of adrenergic and dopaminergic systems by simultaneous prophylactic application of adrenaline (alpha- and beta-receptor stimulant) and bromocriptine (dopamine receptor agonist) may significantly reduce restraint stress lesions development provides insight for further research on the beneficial mechanism of BPC 157.

Joint chemical agent detector (JCAD): the future of chemical agent detection

NASA Astrophysics Data System (ADS)

Laljer, Charles E.

2003-08-01

The Joint Chemical Agent Detector (JCAD) has continued development through 2002. The JCAD has completed Contractor Validation Testing (CVT) that included chemical warfare agent testing, environmental testing, electromagnetic interferent testing, and platform integration validation. The JCAD provides state of the art chemical warfare agent detection capability to military and homeland security operators. Intelligence sources estimate that over twenty countries have active chemical weapons programs. The spread of weapons of mass destruction (and the industrial capability for manufacture of these weapons) to third world nations and terrorist organizations has greatly increased the chemical agent threat to U.S. interests. Coupled with the potential for U.S. involvement in localized conflicts in an operational or support capacity, increases the probability that the military Joint Services may encounter chemical agents anywhere in the world. The JCAD is a small (45 in3), lightweight (2 lb.) chemical agent detector for vehicle interiors, aircraft, individual personnel, shipboard, and fixed site locations. The system provides a common detection component across multi-service platforms. This common detector system will allow the Joint Services to use the same operational and support concept for more efficient utilization of resources. The JCAD detects, identifies, quantifies, and warns of the presence of chemical agents prior to onset of miosis. Upon detection of chemical agents, the detector provides local and remote audible and visual alarms to the operators. Advance warning will provide the vehicle crew and other personnel in the local area with the time necessary to protect themselves from the lethal effects of chemical agents. The JCAD is capable of being upgraded to protect against future chemical agent threats. The JCAD provides the operator with the warning necessary to survive and fight in a chemical warfare agent threat environment.

Hormonal prevention of breast cancer: Mimicking the protective effect of pregnancy

PubMed Central

Guzman, Raphael C.; Yang, Jason; Rajkumar, Lakshmanaswamy; Thordarson, Gudmundur; Chen, Xiaoyan; Nandi, Satyabrata

1999-01-01

Full term pregnancy early in life is the most effective natural protection against breast cancer in women. Rats treated with chemical carcinogen are similarly protected by a previous pregnancy from mammary carcinogenesis. Proliferation and differentiation of the mammary gland does not explain this phenomenon, as shown by the relative ineffectiveness of perphenazine, a potent mitogenic and differentiating agent. Here, we show that short term treatment of nulliparous rats with pregnancy levels of estradiol 17β and progesterone has high efficacy in protecting them from chemical carcinogen induced mammary cancers. Because the mammary gland is exposed to the highest physiological concentrations of estradiol and progesterone during full term pregnancy, it is these elevated levels of hormones that likely induce protection from mammary cancer. Thus, it appears possible to mimic the protective effects of pregnancy against breast cancer in nulliparous rats by short term specific hormonal intervention. PMID:10051675

Ningnanmycin inhibits tobacco mosaic virus virulence by binding directly to its coat protein discs

PubMed Central

Li, Xiangyang; Hao, Gefei; Wang, Qingmin; Chen, Zhuo; Ding, Yan; Yu, Lu; Hu, Deyu; Song, Baoan

2017-01-01

Tobacco mosaic virus (TMV) causes severe plant diseases worldwide; however, effective antiviral agents for controlling TMV infections are not available. This lack of effective antiviral agents is mainly due to the poor understanding of potential targets associated with TMV infections. During infection, the coat protein (CP), which is delivered by viral particles into susceptible host cells, provides protection for viral RNA. Here, we found that Ningnanmycin (NNM), a commercially used plant antibacterial agent, inhibits the assembly of the CP by directly binding several residues. These interactions cause the disassembly of the CP from discs into monomers, leading to an almost complete loss of pathogenicity. Substitutions in the involved binding residues resulted in mutants that were significantly less sensitive to NNM. Thus, targeting the binding of viral CPs through small molecular agents offers an effective strategy to study the mechanism of NNM. PMID:29137277

[Protective effect of sodium bicarbonate on radiological contrast medium-induced nephropathy in rats].

PubMed

Vattimo, Maria deFátima Fernandes; dos Santos, Juliana Guareschi

2013-06-01

Radiological iodinated contrasts (IC) agents cause acute kidney injury (AKI). To evaluate the renoprotective effect of sodium bicarbonate (Bic) on renal function (creatinine clearance [Clcr], Jaffé, and Clcr mLmin -1 x100 g-1) and the oxidative profile (peroxide excretion, urinary peroxides, urinary malondialdehyde, FOX-2 expression, and thiobarbituric acid reactive substance [TBARS; nmol/mg Cr]) in rats treated with an IC agent. Adult male Wistar rats weighing 250-300 g were treated once daily for 5 days with one of the following treatments: saline (0.9%, 3 mL.kg-1xday-1 intraperitoneally [i.p.]), IC agent (sodium and meglumine ioxitalamate, 3 mL/kg, i.p.), Bic + Saline (3-mL/kg Bic, i.p., 1 h before and after saline treatment), and Bic + IC (3-ml/kg Bic, i.p., 1 h before and after the IC treatment). The IC agent induced AKI, and the antioxidant renoprotective effect of Bic was confirmed (Clcr/TBARS/urinary peroxide: saline group, 0.59+/- 0.03/0.11 +/-0.02/1.29+/- 0.24; Bic+Saline group, 0.58 +/-0.03/0.13+/- 0.02/1.32+/- 0.64; IC group, 0.22 +/- 0.02/0.19 +/- 0.02/4.77 +/- 0.24; Bic +Clgroup, 0.51+/- 0.04/0.13+/- 0.3/1.80+/- 0.04; p<0.05). The protective effect of Bic in the IC-induced AKI was confirmed; hence, Bic administration may be considered as a therapeutic option for patients undergoing IC-enhanced radiography.

Nucleotide excision repair modulates the cytotoxic and mutagenic effects of N-n-butyl-N-nitrosourea in cultured mammalian cells as well as in mouse splenocytes in vivo.

PubMed

Bol, S A; van Steeg, H; van Oostrom, C T; Tates, A D; Vrieling, H; de Groot, A J; Mullenders, L H; van Zeeland, A A; Jansen, J G

1999-05-01

The butylating agent N-n-butyl-N-nitrosourea (BNU) was employed to study the role of nucleotide excision repair (NER) in protecting mammalian cells against the genotoxic effects of monofunctional alkylating agents. The direct acting agent BNU was found to be mutagenic in normal and XPA mouse splenocytes after a single i.p. treatment in vivo. After 25 and 35 mg/kg BNU, but not after 75 mg/ kg, 2- to 3-fold more hprt mutants were detected in splenocytes from XPA mice than from normal mice. Using O6-alkylguanine-DNA alkyltransferase (AGT)-deficient hamster cells, it was found that NER-deficient CHO UV5 cells carrying a mutation in the ERCC-2 gene were 40% more mutable towards lesions induced by BNU when compared with parental NER-proficient CHO AA8 cells. UV5 cells were 1.4-fold more sensitive to the cytotoxic effects of BNU compared with AA8 cells. To investigate whether this increased sensitivity of NER-deficient cells is modulated by AGT activity, cell survival studies were performed in human and mouse primary fibroblasts as well. BNU was 2.7-fold more toxic for mouse XPA fibroblasts compared with normal mouse fibroblasts. Comparable results were found for human fibroblasts. Taken together these data indicate that the role of NER in protecting rodent cells against the mutagenic and cytotoxic effects of the alkylating agent BNU depends on AGT.

Serum metabonomic analysis of protective effects of Curcuma aromatica oil on renal fibrosis rats.

PubMed

Zhao, Liangcai; Zhang, Haiyan; Yang, Yunjun; Zheng, Yongquan; Dong, Minjian; Wang, Yaqiang; Bai, Guanghui; Ye, Xinjian; Yan, Zhihan; Gao, Hongchang

2014-01-01

Curcuma aromatica oil is a traditional herbal medicine demonstrating protective and anti-fibrosis activities in renal fibrosis patients. However, study of its mechanism of action is challenged by its multiple components and multiple targets that its active agent acts on. Nuclear magnetic resonance (NMR)-based metabonomics combined with clinical chemistry and histopathology examination were performed to evaluate intervening effects of Curcuma aromatica oil on renal interstitial fibrosis rats induced by unilateral ureteral obstruction. The metabolite levels were compared based on integral values of serum 1H NMR spectra from rats on 3, 7, 14, and 28 days after the medicine administration. Time trajectory analysis demonstrated that metabolic profiles of the agent-treated rats were restored to control levels after 7 days of dosage. The results confirmed that the agent would be an effective anti-fibrosis medicine in a time-dependent manner, especially in early renal fibrosis stage. Targeted metabolite analysis showed that the medicine could lower levels of lipid, acetoacetate, glucose, phosphorylcholine/choline, trimethylamine oxide and raise levels of pyruvate, glycine in the serum of the rats. Serum clinical chemistry and kidney histopathology examination dovetailed well with the metabonomics data. The results substantiated that Curcuma aromatica oil administration can ameliorate renal fibrosis symptoms by inhibiting some metabolic pathways, including lipids metabolism, glycolysis and methylamine metabolism, which are dominating targets of the agent working in vivo. This study further strengthens the novel analytical approach for evaluating the effect of traditional herbal medicine and elucidating its molecular mechanism.

Effects of subacute pretreatment with carbamate together with acute adjunct pretreatment against nerve agent exposure. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, D.R.; Harris, L.W.; Lennox, W.J.

1991-12-31

Acute carbamate pretreatment, in conjunction with atropine pretreatment or followed by atropine and oxime therapy has been shown to protect rabbits, rats, guinea pigs and monkeys against multiple lethal doses of soman. In those experiments, pretreated animals were usually challenged with soman at the time of peak whole blood acetylcholinesterase (AChE) inhibition by the carbamate or when the concentration of carbamate in the blood was expected to be rapidly diminishing. However, soldiers in a chemical environment, having taken carbamate orally might well be exposed to nerve agent shortly thereafter. Thus, both active carbamate and nerve agent would be entering themore » blood simultaneously. In a recent study it was reported that subacute administration of physostigmine (Phy), via subcutaneously implanted 28 day osmotic minipump, afforded protection against an iv challenge of soman on the 27th day.« less

ActRII blockade protects mice from cancer cachexia and prolongs survival in the presence of anti-cancer treatments.

PubMed

Hatakeyama, Shinji; Summermatter, Serge; Jourdain, Marie; Melly, Stefan; Minetti, Giulia C; Lach-Trifilieff, Estelle

2016-01-01

Cachexia affects the majority of patients with advanced cancer and is associated with reduced treatment tolerance, response to therapy, quality of life, and life expectancy. Cachectic patients with advanced cancer often receive anti-cancer therapies against their specific cancer type as a standard of care, and whether specific ActRII inhibition is efficacious when combined with anti-cancer agents has not been elucidated yet. In this study, we evaluated interactions between ActRII blockade and anti-cancer agents in CT-26 mouse colon cancer-induced cachexia model. CDD866 (murinized version of bimagrumab) is a neutralizing antibody against the activin receptor type II (ActRII) preventing binding of ligands such as myostatin and activin A, which are involved in cancer cachexia. CDD866 was evaluated in association with cisplatin as a standard cytotoxic agent or with everolimus, a molecular-targeted agent against mammalian target of rapamycin (mTOR). In the early studies, the treatment effect on cachexia was investigated, and in the additional studies, the treatment effect on progression of cancer and the associated cachexia was evaluated using body weight loss or tumor volume as interruption criteria. Cisplatin accelerated body weight loss and tended to exacerbate skeletal muscle loss in cachectic animals, likely due to some toxicity of this anti-cancer agent. Administration of CDD866 alone or in combination with cisplatin protected from skeletal muscle weight loss compared to animals receiving only cisplatin, corroborating that ActRII inhibition remains fully efficacious under cisplatin treatment. In contrast, everolimus treatment alone significantly protected the tumor-bearing mice against skeletal muscle weight loss caused by CT-26 tumor. CDD866 not only remains efficacious in the presence of everolimus but also showed a non-significant trend for an additive effect on reversing skeletal muscle weight loss. Importantly, both combination therapies slowed down time-to-progression. Anti-ActRII blockade is an effective intervention against cancer cachexia providing benefit even in the presence of anti-cancer therapies. Co-treatment comprising chemotherapies and ActRII inhibitors might constitute a promising new approach to alleviate chemotherapy- and cancer-related wasting conditions and extend survival rates in cachectic cancer patients.

(-)-Phenserine Attenuates Soman-Induced Neuropathology

PubMed Central

Chen, Jun; Pan, Hongna; Chen, Cynthia; Wu, Wei; Iskandar, Kevin; He, Jeffrey; Piermartiri, Tetsade; Jacobowitz, David M.; Yu, Qian-Sheng; McDonough, John H.; Greig, Nigel H.; Marini, Ann M.

2014-01-01

Organophosphorus (OP) nerve agents are deadly chemical weapons that pose an alarming threat to military and civilian populations. The irreversible inhibition of the critical cholinergic degradative enzyme acetylcholinesterase (AChE) by OP nerve agents leads to cholinergic crisis. Resulting excessive synaptic acetylcholine levels leads to status epilepticus that, in turn, results in brain damage. Current countermeasures are only modestly effective in protecting against OP-induced brain damage, supporting interest for evaluation of new ones. (-)-Phenserine is a reversible AChE inhibitor possessing neuroprotective and amyloid precursor protein lowering actions that reached Phase III clinical trials for Alzheimer's Disease where it exhibited a wide safety margin. This compound preferentially enters the CNS and has potential to impede soman binding to the active site of AChE to, thereby, serve in a protective capacity. Herein, we demonstrate that (-)-phenserine protects neurons against soman-induced neuronal cell death in rats when administered either as a pretreatment or post-treatment paradigm, improves motoric movement in soman-exposed animals and reduces mortality when given as a pretreatment. Gene expression analysis, undertaken to elucidate mechanism, showed that (-)-phenserine pretreatment increased select neuroprotective genes and reversed a Homer1expression elevation induced by soman exposure. These studies suggest that (-)-phenserine warrants further evaluation as an OP nerve agent protective strategy. PMID:24955574

Nutrition in emergencies: Issues involved in ensuring proper nutrition in post-chemical, biological, radiological, and nuclear disaster

PubMed Central

Singh, Som Nath

2010-01-01

Accidental or deliberate exposure to chemical, biological, radiological, and nuclear (CBRN) agents poses considerable threat throughout the world. Under such conditions, ensuring proper nutrition is a difficult task due to contamination of food available in the affected area. Generally, food is not prepared or served in an environment contaminated by CBRN agents. Foods that are properly packed need to be decontaminated from outside before use. These agents get incorporated in to food chain. Therefore, especially the foliage vegetables, milk and meat products from affected area are not fit for consumption. Potassium iodide has protective role, as radioiodine uptake into the thyroid can be blocked by its pharmacological doses. This is most effective when taken before exposure, but still has significant effects up to five to six hours postexposure. The antioxidant vitamins and minerals may be included in therapeutic feeding programs, as they are known to protect against oxidative stress. Minimum requirement of calories and nutrients are similar to other disasters and are discussed in the present review. PMID:21829320

Nutrition in emergencies: Issues involved in ensuring proper nutrition in post-chemical, biological, radiological, and nuclear disaster.

PubMed

Singh, Som Nath

2010-07-01

Accidental or deliberate exposure to chemical, biological, radiological, and nuclear (CBRN) agents poses considerable threat throughout the world. Under such conditions, ensuring proper nutrition is a difficult task due to contamination of food available in the affected area. Generally, food is not prepared or served in an environment contaminated by CBRN agents. Foods that are properly packed need to be decontaminated from outside before use. These agents get incorporated in to food chain. Therefore, especially the foliage vegetables, milk and meat products from affected area are not fit for consumption. Potassium iodide has protective role, as radioiodine uptake into the thyroid can be blocked by its pharmacological doses. This is most effective when taken before exposure, but still has significant effects up to five to six hours postexposure. The antioxidant vitamins and minerals may be included in therapeutic feeding programs, as they are known to protect against oxidative stress. Minimum requirement of calories and nutrients are similar to other disasters and are discussed in the present review.

Pathway-specific effect of caffeine on protection against UV irradiation-induced apoptosis in corneal epithelial cells.

PubMed

Wang, Ling; Lu, Luo

2007-02-01

To define the role of molecular interaction between the UV-induced JNK (c-Jun N-terminal kinase) cascade and corneal epithelial cell apoptosis and protection against apoptosis by caffeine. Rabbit and human corneal epithelial cells were cultured in DMEM/F12 medium containing 10% FBS and 5 microg/mL insulin at 37 degrees C in 5% CO(2). DNA fragmentation and ethidium bromide/acridine orange (EB/AO) nuclear staining were performed to detect cell death. Western blot, immunoprecipitation, and kinase assays were used to measure UV-induced mitogen-activated protein (MAP) kinase activity. UV irradiation-induced apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and MAKK4 (SEK1) upstream from JNK was caffeine sensitive. Caffeine (1,3,7-trimethylxanthine), an agent that is one of the most popular additions to food consumed in the world and a potential enhancer of chemotherapy, effectively protected corneal epithelial cells against apoptosis by its specific effect on the JNK cascade. Theophylline (1,3-dimethylxanthine) exhibited an effect similar to that of caffeine on prevention of UV irradiation-induced apoptosis. However, alterations of either intracellular cAMP or Ca(2+) levels did not alter the effect of caffeine on the JNK signaling pathway. In addition, the blockade of PI3K-like kinases by wortmannin had no impact on the protective effect of caffeine against UV irradiation-induced apoptosis, suggesting that the protective effect of caffeine acts through a specific mechanism involving UV irradiation-induced activation of ASK1 and SEK1. In contrast, caffeine had no effects on melphalan-, hyperosmotic stress-, or IL-1beta-induced activation of the JNK signaling pathway in these cells. UV irradiation stress-induced activation of the ASK1-SEK1-JNK signaling pathway leading to apoptosis is a caffeine-sensitive process, and caffeine, as a multifunctional agent in cells, can specifically interact with the pathway to protect against apoptosis.

Salidroside as a Novel Protective Agent to Improve Red Blood Cell Cryopreservation.

PubMed

Alotaibi, Noha A S; Slater, Nigel K H; Rahmoune, Hassan

2016-01-01

Glycerol and trehalose have been widely examined as protective agents in the cryopreservation of red blood cells (RBCs). However, the effectiveness of these reagents alone on cell viability is moderate. Here, the addition of salidroside attenuated oxidative damage of sheep RBCs prior to and post cryostorage. The supplementation of salidroside to the cryopreservation media containing 10% glycerol improved RBC survival by approximately 61.1±4.8% vs 37.9±4.6%. A smaller effect was seen in RBCs cryopreserved in 300 mM trehalose where the addition of salidroside improved survival by 7.6±0.3%. Furthermore, the addition of salidroside to cold storage solution demonstrated a significant reduction of haemolysis after 4 days for RBCs loaded with either glycerol or trehalose, compared to cells incubated without salidroside. RBCs survival was 2-fold greater following freezing in trehalose, compared with glycerol. After 10 days, salidroside enabled a lower haemolysis of 16.7±1.3% compared to 29.0±8.4% for cells incubated without salidroside. However, salidroside had no effect on RBCs which had been frozen in glycerol as the resulting haemolysis rate by day 10 was approximately 60%. Salidroside increased glutathione reductase activity and decreased lactate dehydrogenase activity. Furthermore, it led to reduced carbonylation of proteins in both glycerol and trehalose loaded cells. Finally, no effect on lipid peroxidation was found in the glycerol loaded RBCs although this was reduced in RBCs loaded with trehalose and salidroside. The present findings confirm the potential use of salidroside as a novel protective agent in cryopreservation and refrigerated storage of sheep RBCs.

Facile fabrication of Ag nanowires for capacitive flexible pressure sensors by liquid polyol reduction method

NASA Astrophysics Data System (ADS)

Wei, Xiongbang; Quan, Yong; Zeng, Hongjuan; Huang, Wen; Li, Weizhi; Liao, Jiaxuan; Chen, Zhi

2018-01-01

The Ag nanowires (AgNWs) were prepared by improved liquid polyol reduction method, and the AgNWs were successfully applied to the capacitive flexible pressure sensors. Firstly, the one-dimensional radial growth conditions of AgNWs were optimized from four aspects of the molecular weight of the protective agent polyvinyl pyrrolidone (PVP), the molar ratio of AgNO3 and PVP, the anion concentration of the metal salt and the reaction temperature. The effect of polymerization degree of protective agent on one-dimensional radial growth of AgNWs was investigated by using three kinds of protective agents PVP-K-30, PVP-K-60 and PVP-K-90. Three different AgNO3 and PVP molar ratios of 1:1, 1:3 and 1:9 were designed, and the effects of PVP adsorption capacity on one-dimensional radial growth of AgNWs were investigated. Three concentrations of 0 mM NaCl, 16 mM NaCl and 32 mM NaCl were designed to study the effects of anion concentration of the metal salt on the nucleation and etching of silver nanoparticles. The effects of reaction temperature on the growth of AgNWs were studied at three different temperatures of 140 °C, 160 °C and 180 °C, and appropriate temperature design was proposed. In this experiment, the products of AgNWs prepared under various conditions were analyzed by UV-vis Spectrum and SEM, and the experimental conditions were optimized from the synthesis mechanism and reaction conditions.

ARSENIC EFFECTS ON TELOMERE AND TELOMERASE ACTIVITY

EPA Science Inventory

Arsenic effects on telomere and telomerase activity. T-C. Zhang, M. T. Schmitt, J. Mo, J. L. Mumford, National Research Council and U.S Environmental Protection Agency, NHEERL, Research Triangle Park, NC 27711
Arsenic is a known carcinogen and also an anticancer agent for acut...

Neferine reduces cisplatin-induced nephrotoxicity by enhancing autophagy via the AMPK/mTOR signaling pathway.

PubMed

Li, Hui; Tang, Yuling; Wen, Long; Kong, Xianglong; Chen, Xuelian; Liu, Ping; Zhou, Zhiguo; Chen, Wenhang; Xiao, Chenggen; Xiao, Ping; Xiao, Xiangcheng

2017-03-11

Cisplatin is one of the most effective chemotherapeutic agents; however, its clinical use is limited by serious side effects of which nephrotoxicity is the most important. Nephrotoxicity induced by cisplatin is closely associated with autophagy reduction and caspase activation. In this study, we investigated whether neferine, an autophagy inducer, had a protective effect against cisplatin-induced nephrotoxicity. In an in vitro cisplatin-induced nephrotoxicity model, we determined that neferine was able to induce autophagy and that pretreatment with neferine not only attenuated cisplatin-induced cell apoptosis but further activated cell autophagy. This pro-survival effect was abolished by the autophagic flux inhibitor chloroquine. Furthermore, neferine pretreatment activated the AMPK/mTOR pathway; however, pharmacological inhibition of AMPK abolished neferine-mediated autophagy and nephroprotection against cisplatin-induced apoptosis. Collectively, our findings suggest for the first time the possible protective mechanism of neferine, which is crucial for its further development as a potential therapeutic agent for cisplatin-induced nephrotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Burkholderia mallei CLH001 Attenuated Vaccine Strain Is Immunogenic and Protects against Acute Respiratory Glanders.

PubMed

Hatcher, Christopher L; Mott, Tiffany M; Muruato, Laura A; Sbrana, Elena; Torres, Alfredo G

2016-08-01

Burkholderia mallei is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffective treatment options emphasize its public health threat and highlight the need for a vaccine. Live attenuated vaccines are considered the most viable vaccine strategy for Burkholderia, but single-gene-deletion mutants have not provided complete protection. In this study, we constructed the select-agent-excluded B. mallei ΔtonB Δhcp1 (CLH001) vaccine strain and investigated its ability to protect against acute respiratory glanders. Here we show that CLH001 is attenuated, safe, and effective at protecting against lethal B. mallei challenge. Intranasal administration of CLH001 to BALB/c and NOD SCID gamma (NSG) mice resulted in complete survival without detectable colonization or abnormal organ histopathology. Additionally, BALB/c mice intranasally immunized with CLH001 in a prime/boost regimen were fully protected against lethal challenge with the B. mallei lux (CSM001) wild-type strain. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Transcriptional Inducers of Acetylcholinesterase Expression as Novel Antidotes for Protection Against Chemical Warfare Agents

DTIC Science & Technology

2005-10-01

neuroblastoma cell line , P19 and a human neuroblastoma cell line SH - SY5Y (data not shown). Effect of trichostatin A on...mouse neuroblastoma P19 cell line and a human neuroblastoma cell line SH - SY5Y . More experiments are needed to prove the potential of AChE expression in...treatment of nerve agent exposure. MATERIALS AND METHODS Neuronal cell lines and

MFIRE-2: A Multi Agent System for Flow-Based Intrusion Detection Using Stochastic Search

DTIC Science & Technology

2012-03-01

attacks that are distributed in nature , but may not protect individual systems effectively without incurring large bandwidth penalties while collecting...system-level information to help prepare for more significant attacks. The type of information potentially revealed by footprinting includes account...key areas where MAS may be appropriate: • The environment is open, highly dynamic, uncertain, or complex • Agents are a natural metaphor—Many

Radioprotective Agents: Strategies and Translational Advances.

PubMed

Kamran, Mohammad Zahid; Ranjan, Atul; Kaur, Navrinder; Sur, Souvik; Tandon, Vibha

2016-05-01

Radioprotectors are agents required to protect biological system exposed to radiation, either naturally or through radiation leakage, and they protect normal cells from radiation injury in cancer patients undergoing radiotherapy. It is imperative to study radioprotectors and their mechanism of action comprehensively, looking at their potential therapeutic applications. This review intimately chronicles the rich intellectual, pharmacological story of natural and synthetic radioprotectors. A continuous effort is going on by researchers to develop clinically promising radioprotective agents. In this article, for the first time we have discussed the impact of radioprotectors on different signaling pathways in cells, which will create a basis for scientific community working in this area to develop novel molecules with better therapeutic efficacy. The bright future of exceptionally noncytotoxic derivatives of bisbenzimidazoles is also described as radiomodulators. Amifostine, an effective radioprotectant, has been approved by the FDA for limited clinical use. However, due to its adverse side effects, it is not routinely used clinically. Recently, CBLB502 and several analog of a peptide are under clinical trial and showed high success against radiotherapy in cancer. This article reviews the different types of radioprotective agents with emphasis on the strategies for the development of novel radioprotectors for drug development. In addition, direction for future strategies relevant to the development of radioprotectors is also addressed. © 2016 Wiley Periodicals, Inc.

Pharmacological management of acute radiation morbidity.

PubMed

Zimmermann, J S; Kimmig, B

1998-11-01

The acute radiation morbidity may be a serious problem for the patient and may be decreased by pharmacological approaches. A database research (Medline, Cancerlit, DIMDI, etc.) was performed in order to obtain pharmacological approaches to decrease the acute radiation morbidity. The evaluation was focused on therapeutic principles but not on special drugs. Different approaches may be chosen to protect healthy tissues from the effects of ionizing radiation: 1. administration of cyto- or radioprotective agents prior to irradiation, 2. administration of agents to avoid additional secondary toxicity by inflammation or superinfection during the treatment cycle (supportive care) and 3. administration of rescue agents, such as bone marrow CSFs or hyperbaric oxygen (HBO), after therapy. For radioprotection, there are reports on cellular protection by vitamine E, vitamine C, beta carotene, ribose-cysteine, glutamine, Mgcl2/adenosine triphosphate and WR-2721 (amifostine). In general, preclinical studies show that the combination of pretreatment with amifostine, irradiation, and G-CSF after radiation enhances hematologic recovery. Assessment of these combined effects, including local supportive therapies, merits further clinical investigation. There are data from prospective studies as well as from empirical clinical experience, that radioprotection and clinical supportive care may reduce the treatment related morbidity by 10 to 30% either. A further improvement of the therapeutic ratio is to be expected by systemically combined application of radioprotectors, supportive care and rescue agents.

Minutes of the 23rd Eplosives Safety Seminar, volume 2

NASA Astrophysics Data System (ADS)

1988-08-01

Some areas of discussion at this seminar were: Hazards and risks of the disposal of chemical munitions using a cryogenic process; Special equipment for demilitarization of lethal chemical agent filled munitions; explosive containment room (ECR) repair Johnston Atoll chemical agent disposal system; Sympathetic detonation testing; Blast loads, external and internal; Structural reponse testing of walls, doors, and valves; Underground explosion effects, external airblast; Explosives shipping, transportation safety and port licensing; Explosive safety management; Underground explosion effects, model test and soil rock effects; Chemical risk and protection of workers; and Full scale explosives storage test.

[Biological and toxin terrorism weapons].

PubMed

Bokan, Slavko

2003-03-01

The use of biological agents and toxins in warfare and terrorism has a long history. Human, animal and plant pathogens and toxins can cause disease and can be used as a threat to humans, animals and staple crops. The same is true for biological agents. Although the use of biological agents and toxins in military conflicts has been a concern of military communities for many years, several recent events have increased the awareness of terrorist use of these weapons against civilian population. A Mass Casualty Biological (Toxin) Weapon (MCBTW) is any biological and toxin weapon capable of causing death or disease on a large scale, such that the military or civilian infrastructure of the state or organization being attacked is overwhelmed. A militarily significant (or terrorist) weapon is any weapon capable of affecting, directly or indirectly, that is physically or psychologically, the outcome of a military operation. Although many biological agents such as toxins and bioregulators can be used to cause diseases, there are only a few that can truly threaten civilian populations on a large scale. Bioregulators or modulators are biochemical compounds, such as peptides, that occur naturally in organisms. They are new class of weapons that can damage nervous system, alter moods, trigger psychological changes and kill. The potential military or terrorist use of bioregulators is similar to that of toxins. Some of these compounds are several hundred times more potent than traditional chemical warfare agents. Important features and military advantages of new bioregulators are novel sites of toxic action; rapid and specific effects; penetration of protective filters and equipment, and militarily effective physical incapacitation. This overview of biological agents and toxins is largely intended to help healthcare providers on all levels to make decisions in protecting general population from these agents.

Chemical modification of normal tissue damage induced by photodynamic therapy.

PubMed Central

Sigdestad, C. P.; Fingar, V. H.; Wieman, T. J.; Lindberg, R. D.

1996-01-01

One of the limitations of successful use of photodynamic therapy (PDT) employing porphyrins is the acute and long-term cutaneous photosensitivity. This paper describes results of experiments designed to test the effects of two radiation protective agents (WR-2721, 500 mg kg-1 or WR-3689, 700 mg kg-1) on murine skin damage induced by PDT. C3H mice were shaved and depilated three days prior to injection with the photosensitiser, Photofrin (5 or 10 mg kg-1). Twenty-four hours later, the mice were injected intraperitoneally with a protector 30 min prior to Argon dye laser (630 nm) exposure. The skin response was followed for two weeks post irradiation using an arbitrary response scale. A light dose response as well as a drug dose response was obtained. The results indicate that both protectors reduced the skin response to PDT, however WR-2721 was demonstrated to be the most effective. The effect of the protectors on vascular stasis after PDT was determined using a fluorescein dye exclusion assay. In mice treated with Photofrin (5 mg kg-1), and 630 nm light (180 J cm-2) pretreatment with either WR-2721 or WR-3689 resulted in significant protection of the vascular effects of PDT. These studies document the ability of the phosphorothioate class of radiation protective agents to reduce the effects of light on photosensitized skin. They do so in a drug dose-dependent fashion with maximum protection at the highest drug doses. PMID:8763855

Zinc dependent Histone deacetylase inhibitors in cancer therapeutics: Recent update.

PubMed

Georgianos, Panagiotis I; Divani, Maria; Eleftheriadis, Theodoros; Mertens, Peter R; Liakopoulos, Vassilios

2018-05-23

Despite optimal management of diabetic kidney disease (DKD) with intensive glycemic control and administration of agents blocking the renin-angiotensin-aldosterone-system, the residual risk for nephropathy progression to end-stage-renal-disease (ESRD) remains high. Sodium-glucose co-transporter type 2 (SGLT-2)-inhibitors represent a newly-introduced anti-diabetic drug class with pleiotropic actions extending above their glucose-lowering efficacy. Herein, we provide an overview of preclinical and clinical-trial evidence supporting a protective effect of SGLT-2 inhibitors on DKD. A systematic literature search of bibliographic databases to identify preclinical studies and randomized trials evaluating the effects SGLT-2 inhibitors on DKD. Preclinical studies performed in animal models of DKD support the renoprotective action of SGLT-2 inhibitors showing that these agents exert albuminuria-lowering effects and reverse glomerulosclerosis. The renoprotective action of SGLT-2 inhibitors is strongly supported by human studies showing that these agents prevent the progression of albuminuria and retard nephropathy progression to ESRD. This beneficial effect of SGLT-2 inhibitors is not fully explained by their glucose-lowering properties. Attenuation of glomerular hyperfiltration and improvement in a number of surrogate risk factors, including associated reduction in systemic blood pressure, body weight, and serum uric acid levels may represent plausible mechanistic explanations for the cardio-renal protection offered by SGLT-2 inhibitors. Furthermore, the tubular cell metabolism seems to be altered towards a ketone-prone pathway with protective activities. SGLT-2 inhibition emerges as a novel therapeutic approach of type 2 diabetes with anticipated benefits towards cardio-renal risk reduction. Additional research efforts are clearly warranted to elucidate this favorable effect in patients with overt DKD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Fire extinguishment and inhibition in spacecraft environments

NASA Technical Reports Server (NTRS)

Deris, John

1987-01-01

It was concluded that it is essential that NASA develop a comprehensive approach to fire extinguishment and inerting in spacecraft environments. Electronic equipment might be easily protected through use of an onboard inert gas generating system. The use of Halon 1301 presents serious technological challenges for agent cleanup and removal of the toxic and corrosive products of combustion. Nitrogen pressurization, while effective, probably presents a serious weight penality. The use of liquid water sprays appears to be the most effective approach to general purpose spacecraft fire protection.

Adenoviral Expression of a Bispecific VHH-Based Neutralizing Agent That Targets Protective Antigen Provides Prophylactic Protection from Anthrax in Mice.

PubMed

Moayeri, Mahtab; Tremblay, Jacqueline M; Debatis, Michelle; Dmitriev, Igor P; Kashentseva, Elena A; Yeh, Anthony J; Cheung, Gordon Y C; Curiel, David T; Leppla, Stephen; Shoemaker, Charles B

2016-01-06

Bacillus anthracis, the causative agent of anthrax, secretes three polypeptides, which form the bipartite lethal and edema toxins (LT and ET, respectively). The common component in these toxins, protective antigen (PA), is responsible for binding to cellular receptors and translocating the lethal factor (LF) and edema factor (EF) enzymatic moieties to the cytosol. Antibodies against PA protect against anthrax. We previously isolated toxin-neutralizing variable domains of camelid heavy-chain-only antibodies (VHHs) and demonstrated their in vivo efficacy. In this work, gene therapy with an adenoviral (Ad) vector (Ad/VNA2-PA) (VNA, VHH-based neutralizing agents) promoting the expression of a bispecific VHH-based neutralizing agent (VNA2-PA), consisting of two linked VHHs targeting different PA-neutralizing epitopes, was tested in two inbred mouse strains, BALB/cJ and C57BL/6J, and found to protect mice against anthrax toxin challenge and anthrax spore infection. Two weeks after a single treatment with Ad/VNA2-PA, serum VNA2-PA levels remained above 1 μg/ml, with some as high as 10 mg/ml. The levels were 10- to 100-fold higher and persisted longer in C57BL/6J than in BALB/cJ mice. Mice were challenged with a lethal dose of LT or spores at various times after Ad/VNA2-PA administration. The majority of BALB/cJ mice having serum VNA2-PA levels of >0.1 μg/ml survived LT challenge, and 9 of 10 C57BL/6J mice with serum levels of >1 μg/ml survived spore challenge. Our findings demonstrate the potential for genetic delivery of VNAs as an effective method for providing prophylactic protection from anthrax. We also extend prior findings of mouse strain-based differences in transgene expression and persistence by adenoviral vectors. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Synergistic neuroprotective therapies with hypothermia

PubMed Central

Cilio, Maria Roberta; Ferriero, Donna M.

2010-01-01

summary Neuroprotection is a major health care priority, given the enormous burden of human suffering and financial cost caused by perinatal brain damage. With the advent of hypothermia as therapy for term hypoxic–ischemic encephalopathy, there is hope for repair and protection of the brain after a profound neonatal insult. However, it is clear from the published clinical trials and animal studies that hypothermia alone will not provide complete protection or stimulate the repair that is necessary for normal neurodevelopmental outcome. This review critically discusses drugs used to treat seizures after hypoxia–ischemia in the neonate with attention to evidence of possible synergies for therapy. In addition, other agents such as xenon, N-acetylcysteine, erythropoietin, melatonin and cannabinoids are discussed as future potential therapeutic agents that might augment protection from hypothermia. Finally, compounds that might damage the developing brain or counteract the neuroprotective effects of hypothermia are discussed. PMID:20207600

76 FR 77914 - Agricultural Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-15

... Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List; Amendments to the Select Agent and Toxin Regulations AGENCY: Animal and Plant Health Inspection Service, USDA... proposed rule that would amend and republish the list of select agents and toxins that have the potential...

Fostering Resilience: Protective Agents, Resources, and Mechanisms for Adolescent Refugees’ Psychosocial Well-Being

PubMed Central

Weine, Stevan Merrill; Ware, Norma; Hakizimana, Leonce; Tugenberg, Toni; Currie, Madeleine; Dahnweih, Gonwo; Wagner, Maureen; Polutnik, Chloe; Wulu, Jacqueline

2014-01-01

Background Adolescent refugees face many challenges but also have the potential to become resilient. The purpose of this study was to identify and characterize the protective agents, resources, and mechanisms that promote their psychosocial well-being. Methods Participants included a purposively sampled group of 73 Burundian and Liberian refugee adolescents and their families who had recently resettled in Boston and Chicago. The adolescents, families, and their service providers participated in a two-year longitudinal study using ethnographic methods and grounded theory analysis with Atlas/ti software. A grounded theory model was developed which describes those persons or entities who act to protect adolescents (Protective Agents), their capacities for doing so (Protective Resources), and how they do it (Protective Mechanisms). Protective agents are the individuals, groups, organizations, and systems that can contribute either directly or indirectly to promoting adolescent refugees’ psychosocial well-being. Protective resources are the family and community capacities that can promote psychosocial well-being in adolescent refugees. Protective mechanisms are the processes fostering adolescent refugees’ competencies and behaviors that can promote their psychosocial well-being. Results Eight family and community capacities were identified that appeared to promote psychosocial well-being in the adolescent refugees. These included 1) finances for necessities; 2) English proficiency; 3) social support networks; 4) engaged parenting; 5) family cohesion; 6) cultural adherence and guidance; 7) educational support; and 8) faith and religious involvement. Nine protective mechanisms identified were identified and grouped into three categories: 1) Relational (supporting, connecting, belonging); 2) Informational (informing, preparing), and; 3) Developmental (defending, promoting, adapting). Conclusions To further promote the psychosocial well-being of adolescent refugees, targeted prevention focused policies and programs are needed to enhance the identified protective agents, resources, and mechanisms. Because resilience works through protective mechanisms, greater attention should be paid to understanding how to enhance them through new programs and practices, especially informational and developmental protective mechanisms. PMID:25544939

Efficacy of abamectin and tebuconazole injections to protect of lodgepole pine from mortality attributed to mountain pine beetle attack and progression of blue stain fungi

Treesearch

Christopher J. Fettig; Donald M. Grosman; A. Steven. Munson

2013-01-01

Bark beetles (Coleoptera: Curculionidae, Scolytinae) are important tree mortality agents in western coniferous forests. Protection of individual trees from bark beetle attack has historically involved applications of liquid formulations of contact insecticides to the tree bole using hydraulic sprayers. More recently, researchers have examined the effectiveness of...

Can You Hear Me Now: The Leading Army Injury & Disability

DTIC Science & Technology

2011-03-07

99 An acute onset of noise induced hearing loss should be treated as an emergency. Prompt management of improving the blood flow to the inner ear...antioxidants to alleviate cochlear damage caused by noise and ototoxicity; supplements could provide an additional layer of protection.117...various compounds used for hearing protection ranging from antioxidants that scavenge free radicals to agents that increase blood flow . Effective

Evaluation of technetium-99m decay on Escherichia coli inactivation: effects of physical or chemical agents.

PubMed Central

Silva, C. R.; Valsa, J. O.; Caniné, M. S.; Caldeira-de-Araújo, A.; Bernardo-Filho, M.

1998-01-01

Technetium-99m (99mTc) has been used in nuclear medicine and in biomedical research to label molecular and cellular structures employed as radiotracers. Here, we have evaluated, on a DNA repair proficient Escherichia coli strain, the 99mTc decay inactivation and the influence of the (i) pre-treatment with metal ion chelators or of the (ii) treatment with a free radical scavenger on the protection of the cells against the lethal effect of the 99mTc. As SnCl2 is frequently used as a reducing agent in the 99mTc-labeling process, we have also studied the capability of SnCl2 to alter the biological effects induced by the 99mTc decay. As we are exposed to either chemical or physical agents in the nature, we have decided to study a possible influence of the ultraviolet solar radiation in the biological phenomena induced by the 99mTc decay. Our data point out (i) a very important role of the Auger and/or conversion electrons in the cytotoxicity induced by the 99mTc decay; (ii) SnCl2, the metal ion chelators and the free radical scavenger protect the cells against the lethal effect of the 99mTc; and (iii) near-UV does not alter the lethal effect of the 99mTc decay. PMID:9713950

Efficacy studies of Reactive Skin Decontamination Lotion, M291 Skin Decontamination Kit, 0.5% bleach, 1% soapy water, and Skin Exposure Reduction Paste Against Chemical Warfare Agents, part 1: guinea pigs challenged with VX.

PubMed

Braue, Ernest H; Smith, Kelly H; Doxzon, Bryce F; Lumpkin, Horace L; Clarkson, Edward D

2011-03-01

This report, first in a series of five, directly compares the efficacy of 4 decontamination products and Skin Exposure Reduction Paste Against Chemical Warfare Agents (SERPACWA) in the haired guinea pig model following exposure to VX. In all experiments, guinea pigs were close-clipped and given anesthesia. In the decontamination experiments, the animals were challenged with VX and decontaminated after a 2-minute delay for the standard procedure or at longer times for the delayed-decontamination experiments. Skin Exposure Reduction Paste Against Chemical Warfare Agents was applied as a thin coating (0.1 mm thick), allowed to dry for 15 minutes, and challenged with VX. After a 2-hour challenge, any remaining VX was blotted off the animal, but no additional decontamination was done. Positive control animals were challenged with VX in the same manner as the treated animals, except that they received no treatment. In addition, the positive control animals were always challenged with 5% VX in isopropyl alcohol (IPA) solution, whereas the treatment animals received either neat (undiluted) VX or 5% VX in IPA solution. All animals were observed during the first 4 hours and again at 24 hours after exposure for signs of toxicity and death. The protective ratio (PR, defined as the median lethal dose [LD(50)] of the treatment group divided by the LD(50) of the untreated positive control animals) was calculated from the probit dose-response curves established for each treatment group and nontreated control animals. Significance in this report was defined as p < .05. In the standard 2-minute neat VX decontamination experiments, the calculated PRs for Reactive Skin Decontamination Lotion (RSDL), 0.5% bleach, 1% soapy water, and the M291 Skin Decontamination Kit (SDK) were 66, 17, 16, and 1.1, respectively. Reactive Skin Decontamination Lotion was by far the most effective decontamination product tested and was significantly better than any of the other products. Bleach and soapy water provided equivalent and good (PR > 5) protection. They were both significantly better than the M291 SDK. The M291 SDK did not provide significant protection compared with positive controls. In the neat VX delayed-decontamination experiments, the calculated LT(50) (the delayed-decontamination time at which 50% of the animals died in the test population following a 5-LD(50) challenge) values for RSDL, 0.5% bleach, and 1% soapy water were 31, 48, and 26 minutes, respectively. The results showed that SERPACWA provided significant, but modest (PR < 5), protection against neat VX, with a PR of 2.1. Several conclusions can be drawn from this study: 1) RSDL provided superior protection against VX compared with the other products tested; 2) 0.5% bleach and 1% soapy water were less effective than RSDL, but still provided good protection against VX; 3) the M291 SDK was the least effective decontamination product and did not provide significant protection against VX; 4) the agent was observed to streak when using the M291 SDK, and efficacy may improve if the agent is first blotted, followed by wiping with a new or clean part of the M291 SDK pad; 5) RSDL, 0.5% bleach, and 1% soapy water provided significant protection against a 5-LD(50) challenge of VX, even when decontamination was delayed for up to about 30 minutes; and 6) SERPACWA provided significant, but modest, protection against VX.

Vaccine herd effect

PubMed Central

Kim, Tae Hyong; Johnstone, Jennie; Loeb, Mark

2011-01-01

Vaccination ideally protects susceptible populations at high risk for complications of the infection. However, vaccines for these subgroups do not always provide sufficient effectiveness. The herd effect or herd immunity is an attractive way to extend vaccine benefits beyond the directly targeted population. It refers to the indirect protection of unvaccinated persons, whereby an increase in the prevalence of immunity by the vaccine prevents circulation of infectious agents in susceptible populations. The herd effect has had a major impact in the eradication of smallpox, has reduced transmission of pertussis, and protects against influenza and pneumococcal disease. A high uptake of vaccines is generally needed for success. In this paper we aim to provide an update review on the herd effect, focusing on the clinical benefit, by reviewing data for specific vaccines. PMID:21604922

DNA Vaccines - A Modern Gimmick or a Boon to Vaccinology?

PubMed

Manickan, Elanchezhiyan; Karem, Kevin L; Rouse, Barry T

2017-01-01

The reports in 1993 that naked DNA encoding viral genes conferred protective immunity came as a surprise to most vaccinologists. This review analyses the expanding number of examples where plasmid DNA induces immune responses. Issues such as the type of immunity induced, mechanisms of immune protection, and how DNA vaccines compare with other approaches are emphasized. Additional issues discussed include the likely means by which DNA vaccines induce CTL, how the potency and type of immunity induced can be modified, and whether DNA vaccines represent a practical means of manipulating unwanted immune response occurring during immunoinflammatory diseases. It seems doubtful if DNA vaccines will replace currently effective vaccines, but they may prove useful for prophylactic use against some agents that at present lack an effective vaccine. DNA vaccines promise to be valuable to manipulate the immune response in situations where responses to agents are inappropriate or ineffective.

Effectiveness of expedient sheltering in place in a residence.

PubMed

Jetter, James J; Whitfield, Calvin

2005-03-17

The objective of this study was to evaluate the effectiveness of expedient sheltering in place in a residence for protection against airborne hazards, as outlined in the U.S. Department of Homeland Security (DHS) guidance to the public. An improved method was developed to determine the air flow rate for a shelter inside a house. Expedient sheltering measures (plastic sheeting and duct tape) were applied to a room inside a test house by participants who followed the DHS guidance. Measured air flow rates were used to determine protection factors for various scenarios. Protection factors were calculated for the house and shelter under various occupancy times, weather conditions, and outdoor exposure times for hazardous agents. Protection factors ranged from 1.3 to 539, depending on the conditions. Results indicate that proper sealing can make a substantial difference in the effectiveness of the shelter. Sheltering in place can be most beneficial if people enter shelters before the arrival of a cloud of hazardous agent, and people exit shelters as soon as the cloud passes over. However, sheltering in place can be detrimental if people enter or exit shelters too late. CO2 and O2 concentrations inside the shelter are not likely to reach dangerous levels under most scenarios, but concentrations could reach dangerous levels under certain conditions, and concentration levels could affect individuals with respiratory problems.

Performance evaluation of two protective treatments on salt-laden limestones and marble after natural and artificial weathering.

PubMed

Salvadori, Barbara; Pinna, Daniela; Porcinai, Simone

2014-02-01

Salt crystallization is a major damage factor in stone weathering, and the application of inappropriate protective products may amplify its effects. This research focuses on the evaluation of two protective products' performance (organic polydimethylsiloxane and inorganic ammonium oxalate (NH4)2(COO)2·H2O) in the case of a salt load from behind. Experimental laboratory simulations based on salt crystallization cycles and natural weathering in an urban area were carried out. The effects were monitored over time, applying different methods: weight loss evaluation, colorimetric and water absorption by capillarity measurements, stereomicroscope observations, FTIR and SEM-EDS analyses. The results showed minor impact exerted on the short term on stones, particularly those treated with the water repellent, by atmospheric agents compared to salt crystallization. Lithotypes with low salt load (Gioia marble) underwent minor changes than the heavily salt-laden limestones (Lecce and Ançã stones), which were dramatically damaged when treated with polysiloxane. The results suggest that the ammonium oxalate treatment should be preferred to polysiloxane in the presence of soluble salts, even after desalination procedures which might not completely remove them. In addition, the neo-formed calcium oxalate seemed to effectively protect the stone, improving its resistance against salt crystallization without occluding the pores and limiting the superficial erosion caused by atmospheric agents.

Pharmacological strategies for protection of extrahepatic islet transplantation.

PubMed

Omori, K; Komatsu, H; Rawson, J; Mullen, Y

2015-06-01

The safety and effectiveness of islet transplantation has been proven through world-wide trials. However, acute and chronic islet loss has hindered the ultimate objective of becoming a widely used treatment option for type 1 diabetes. A large islet loss is attributed, in part, to the liver being a less-than-optimal site for transplantation. Over half of the transplanted islets are destroyed shortly after transplantation due to direct exposure to blood and non-specific inflammation. Successfully engrafted islets are continuously exposed to the liver micro-environment, a unique immune system, low oxygen tension, toxins and high glucose, which is toxic to islets, leading to premature islet dysfunction/death. Investigations have continued to search for alternate sites to transplant islets that provide a better environment for prolonged function and survival. This article gathers courses and conditions that lead to islet loss, from organ procurement through islet transplantation, with special emphasis on hypoxia, oxidative stress, and antigen non-specific inflammation, and reviews strategies using pharmacological agents that have shown effectiveness in protecting islets, including a new treatment approach utilizing siRNA. Pharmacological agents that support islet survival and promote β-cell proliferation are also included. Treatment of donor pancreata and/or islets with these agents should increase the effectiveness of islets transplanted into extrahepatic sites. Furthermore, the development of methods designed to release these agents over an extended period, will further increase their efficacy. This requires the combined efforts of both islet transplant biologists and bioengineers.

Protective Effect of Anti-Phosphatidylserine Antibody in a Guinea Pig Model of Advanced Hemorrhagic Arenavirus Infection.

PubMed

Thomas, John M; Thorpe, Philip E

2017-01-01

Host derived markers on virally infected cells or virions may provide targets for the generation of antiviral agents. Recently, we identified phosphatidylserine (PS) as a host marker of virions and virally-infected cells. Under normal physiological conditions, PS is maintained on the inner leaflet of the plasma membrane facing the cytosol. Following viral infection, activation or pre-apoptotic changes cause PS to become externalized. We have previously shown that bavituximab, a chimeric human-mouse antibody that binds PS complexed with β2-glycoprotein I (β2GP1), protected rodents against lethal Pichinde virus and cytomegalovirus infections. Here, we determined the antiviral activity of a fully human monoclonal antibody, PGN632, that directly binds to PS. Treatment with PGN632 protected 20% of guinea pigs with advanced infections of the hemorrhagic arenavirus, Pichinde, from death. Combining PGN632 with ribavirin improved the antiviral activity of both agents, such that the combination rescued 50% of animals from death. The major mechanisms of action of PGN632 appear to be opsonization of virus and antibody-dependent cellular cytotoxicity of virally-infected cells. PS-targeting agents may have utility in the treatment of viral diseases.

Effect of solubilizing agents on mupirocin loading into and release from PEGylated nanoliposomes.

PubMed

Cern, Ahuva; Nativ-Roth, Einat; Goldblum, Amiram; Barenholz, Yechezkel

2014-07-01

Mupirocin was identified by quantitative structure property relationship models as a good candidate for remote liposomal loading. Mupirocin is an antibiotic that is currently restricted to topical administration because of rapid hydrolysis in vivo to its inactive metabolite. Formulating mupirocin in PEGylated nanoliposomes may potentially expand its use to parenteral administration by protecting it from degradation in the circulation and target it (by the enhanced permeability effect) to the infected tissue. Mupirocin is slightly soluble in aqueous medium and its solubility can be increased using solubilizing agents. The effect of the solubilizing agents on mupirocin remote loading was studied when the solubilizing agents were added to the drug loading solution. Propylene glycol was found to increase mupirocin loading, whereas polyethylene glycol 400 showed no effect. Hydroxypropyl-β-cyclodextrin (HPCD) showed a concentration-dependent effect on mupirocin loading; using the optimal HPCD concentration increased loading, but higher concentrations inhibited it. The inclusion of HPCD in the liposome aqueous phase while forming the liposomes resulted in increased drug loading and substantially inhibited drug release in serum. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

75 FR 44724 - Agricultural Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-29

... Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select Agent and Toxin List; Reorganization of the Select Agent and Toxin List AGENCY: Animal and Plant Health Inspection Service, USDA... Agricultural Bioterrorism Protection Act of 2002, we are soliciting public comment regarding the list of select...

The use of nicotinamide in the prevention of type 1 diabetes.

PubMed

Elliott, R B; Pilcher, C C; Stewart, A; Fergusson, D; McGregor, M A

1993-11-30

Nicotinamide can protect the NOD mouse from diabetes if given early enough and in sufficient dose. The effect partly wanes with time. There is reduced islet inflammation. Similar protective effects can be demonstrated in quasi-experimental interventions in humans--both diabetes related and unrelated deemed at risk of developing diabetes by reason of having islet cell antibodies. Nicotinamide protects isolated islets in vitro from the toxicity of a number of agents, but only in doses that produce significant PARP inhibition, and increased intracellular levels of NAD. It is unlikely that the protective effect demonstrated in humans is due to significant PARP inhibition, as the levels of nicotinamide achieved with the doses used are too low. Other effects of the vitamin are more likely, e.g., increase in NAD pool size by de novo synthesis, or inhibition of free radical generation. The drug appears to be safe in the doses employed in humans.

Atypical pattern of (meth)acrylate allergic contact dermatitis in dental professionals.

PubMed

Prasad Hunasehally, R Y; Hughes, T M; Stone, N M

2012-09-01

(Meth)acrylates in dental bonding agents are a common source of allergic contact dermatitis in dental professionals. The distribution of the contact dermatitis is commonly on finger tips, but is determined by individual habits as demonstrated by the two case reports in this article. Despite the site of contact dermatitis, the bonding agents are often not suspected as a source of contact allergy due to misconception regarding the protective effect of natural rubber latex gloves. With these case reports, we endeavour to emphasize the inadequacy of the latex gloves in protecting against the (meth)acrylate induced contact allergy and also list the measures a dental professional needs to incorporate in order to minimise the risks of sensitisation to (meth)acrylates.

The protective effect of calcium against genotoxicity of lead acetate administration on bone marrow and spermatocyte cells of mice in vivo.

PubMed

Aboul-Ela, Ezzat I

2002-04-26

The protective effect of calcium given orally by gavage with two doses (40 and 80mg/kg body weight) was evaluated against clastogenecity induced by lead acetate with two concentrations (200 and 400mg/kg diet) on bone marrow and spermatocyte cells of mice in vivo. The parameter screened was percentage of chromosomal aberrations with and without gaps and sperm abnormalities. Statistical analyses indicated the protection efficacy of calcium with the high dose rather than the other in both types of mouse cells. The observation from the laboratory tests, dealing that lead acetate can be considered as an environmental genotoxic material. We recommended that it must be administered of calcium (as calcium chloride) as a protective agent to reduce the genotoxic effect of lead in the somatic and germ cells.

Aviation Engine Test Facilities (AETF) fire protection study

NASA Astrophysics Data System (ADS)

Beller, R. C.; Burns, R. E.; Leonard, J. T.

1989-07-01

An analysis is presented to the effectiveness of various types of fire fighting agents in extinguishing the kinds of fires anticipated in Aviation Engine Test Facilities (AETF), otherwise known as Hush Houses. The agents considered include Aqueous Film-Forming Foam, Halon 1301, Halon 1211 and water. Previous test work has shown the rapidity with which aircraft, especially high performance aircraft, can be damaged by fire. Based on this, tentative criteria for this evaluation included a maximum time of 20 s from fire detection to extinguishment and a period of 30 min in which the agent would prevent reignition. Other issues examined included: toxicity, corrosivity, ease of personnel egress, system reliability, and cost effectiveness. The agents were evaluated for their performance in several fire scenarios, including: under frame fire, major engine fire, engine disintegration fire, high-volume pool fire with simultaneous spill fire, internal electrical fire, and runaway engine fire.

Sofalcone, a gastric mucosa protective agent, increases vascular endothelial growth factor via the Nrf2-heme-oxygenase-1 dependent pathway in gastric epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shibuya, Akiko; Onda, Kenji, E-mail: knjond@toyaku.ac.jp; Kawahara, Hirofumi

2010-07-30

Research highlights: {yields} Sofalcone increases HO-1 in gastric epithelial cells. {yields} The induction of HO-1 by sofalcone treatment follows the activation of Nrf2. {yields} The production of VEGF by sofalcone treatment is mediated by HO-1 induction. -- Abstract: Sofalcone, 2'-carboxymethoxy-4,4-bis(3-methyl-2-butenyloxy)chalcone, is an anti-ulcer agent that is classified as a gastric mucosa protective agent. Recent studies indicate heat shock proteins such as HSP32, also known as heme-oxygenase-1(HO-1), play important roles in protecting gastrointestinal tissues from several stresses. We have previously reported that sofalcone increases the expression of HO-1 in adipocytes and pre-adipocytes, although the effect of sofalcone on HO-1 induction inmore » gastrointestinal tissues is not clear. In the current study, we investigated the effects of sofalcone on the expression of HO-1 and its functional role in rat gastric epithelial (RGM-1) cells. We found that sofalcone increased HO-1 expression in RGM-1 cells in both time- and concentration-dependent manners. The HO-1 induction was associated with the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in RGM-1 cells. We also observed that sofalcone increased vascular endothelial growth factor (VEGF) production in the culture medium. Treatment of RGM-1 cells with an HO-1 inhibitor (tin-protoporphyrin), or HO-1 siRNA inhibited sofalcone-induced VEGF production, suggesting that the effect of sofalcone on VEGF expression is mediated by the HO-1 pathway. These results suggest that the gastroprotective effects of sofalcone are partly exerted via Nrf2-HO-1 activation followed by VEGF production.« less

Burkholderia terrae BS001 migrates proficiently with diverse fungal hosts through soil and provides protection from antifungal agents

PubMed Central

Nazir, Rashid; Tazetdinova, Diana I.; van Elsas, Jan Dirk

2014-01-01

Soil bacteria can benefit from co-occurring soil fungi in respect of the acquisition of carbonaceous nutrients released by fungal hyphae and the access to novel territories in soil. Here, we investigated the capacity of the mycosphere-isolated bacterium Burkholderia terrae BS001 to comigrate through soil along with hyphae of the soil fungi Trichoderma asperellum, Rhizoctonia solani, Fusarium oxysporum, F. oxysporum pv lini, Coniochaeta ligniaria, Phanerochaete velutina, and Phallus impudicus. We used Lyophyllum sp. strain Karsten as the reference migration-inciting fungus. Bacterial migration through presterilized soil on the extending fungal hyphae was detected with six of the seven test fungi, with only Phallus impudicus not showing any bacterial transport. Much like with Lyophyllum sp. strain Karsten, intermediate (106–108 CFU g-1 dry soil) to high (>108 CFU g-1 dry soil) strain BS001 cell population sizes were found at the hyphal migration fronts of four fungi, i.e., T. asperellum, Rhizoctonia solani, F. oxysporum and F. oxysporum pv lini, whereas for two fungi, Coniochaeta ligniaria and Phanerochaete velutina, the migration responses were retarded and population sizes were lower (103–106 CFU g-1 dry soil). Consistent with previous data obtained with the reference fungus, migration with the migration-inciting fungi occurred only in the direction of the hyphal growth front. Remarkably, Burkholderia terrae BS001 provided protection from several antifungal agents to the canonical host Lyophyllum sp. strain Karsten. Specifically, this host was protected from Pseudomonas fluorescens strain CHA0 metabolites, as well as from the anti-fungal agent cycloheximide. Similar protection by strain BS001was observed for T. asperellum, and, to a lower extent, F. oxysporum and Rhizoctonia solani. The protective effect may be related to the consistent occurrence of biofilm-like cell layers or agglomerates at the surfaces of the protected fungi. The current study represents the first report of protection of soil fungi against antagonistic agents present in the soil provided by fungal-associated Burkholderia terrae cells. PMID:25426111

Biomaterials for mediation of chemical and biological warfare agents.

PubMed

Russell, Alan J; Berberich, Jason A; Drevon, Geraldine F; Koepsel, Richard R

2003-01-01

Recent events have emphasized the threat from chemical and biological warfare agents. Within the efforts to counter this threat, the biocatalytic destruction and sensing of chemical and biological weapons has become an important area of focus. The specificity and high catalytic rates of biological catalysts make them appropriate for decommissioning nerve agent stockpiles, counteracting nerve agent attacks, and remediation of organophosphate spills. A number of materials have been prepared containing enzymes for the destruction of and protection against organophosphate nerve agents and biological warfare agents. This review discusses the major chemical and biological warfare agents, decontamination methods, and biomaterials that have potential for the preparation of decontamination wipes, gas filters, column packings, protective wear, and self-decontaminating paints and coatings.

Bioprotective carnitinoids: lipoic acid, butyrate, and mitochondria-targeting to treat radiation injury: mitochondrial drugs come of age.

PubMed

Steliou, Kosta; Faller, Douglas V; Pinkert, Carl A; Irwin, Michael H; Moos, Walter H

2015-06-01

Preclinical Research Given nuclear-power-plant incidents such as the 2011 Japanese Fukushima-Daiichi disaster, an urgent need for effective medicines to protect against and treat the harmful biological effects of radiation is evident. To address such a challenge, we describe potential strategies herein including mitochondrial and epigenetic-driven methods using lipoic and butyric acid ester conjugates of carnitine. The antioxidant and other therapeutically beneficial properties of this class of agents may protect against ionizing radiation and resultant mitochondrial dysfunction. Recent studies of the compounds described herein reveal the potential-although further research and development is required to prove the effectiveness of this approach-to provide field-ready radiation-protective drugs. © 2015 Wiley Periodicals, Inc.

Passive Antibody Administration (Immediate Immunity) as a Specific Defense Against Biological Weapons

PubMed Central

2002-01-01

The potential threat of biological warfare with a specific agent is proportional to the susceptibility of the population to that agent. Preventing disease after exposure to a biological agent is partially a function of the immunity of the exposed individual. The only available countermeasure that can provide immediate immunity against a biological agent is passive antibody. Unlike vaccines, which require time to induce protective immunity and depend on the host’s ability to mount an immune response, passive antibody can theoretically confer protection regardless of the immune status of the host. Passive antibody therapy has substantial advantages over antimicrobial agents and other measures for postexposure prophylaxis, including low toxicity and high specific activity. Specific antibodies are active against the major agents of bioterrorism, including anthrax, smallpox, botulinum toxin, tularemia, and plague. This article proposes a biological defense initiative based on developing, producing, and stockpiling specific antibody reagents that can be used to protect the population against biological warfare threats. PMID:12141970

MO-F-CAMPUS-J-01: Effect of Iodine Contrast Agent Concentration On Cerebrovascular Dose for Synchrotron Radiation Microangiography Based On a Simple Mouse Head Model and a Voxel Mouse Head Phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, H; Jing, J; Xie, C

Purpose: To find effective setting methods to mitigate the irradiation injure in synchrotron radiation microangiography(SRA) by Monte Carlo simulation. Methods: A mouse 1-D head model and a segmented voxel mouse head phantom were simulated by EGSnrc/Dosxyznrc code to investigate the dose enhancement effect of the iodine contrast agent irradiated by a monochromatic synchrotron radiation(SR) source. The influence of, like iodine concentration (IC), vessel width and depth, with and without skull layer protection and the various incident X ray energies, were simulated. The dose enhancement effect and the absolute dose based on the segmented voxel mouse head phantom were evaluated. Results:more » The dose enhancement ratio depends little on the irradiation depth, but strongly on the IC, which is linearly increases with IC. The skull layer protection cannot be ignored in SRA, the 700µm thick skull could decrease 10% of the dose. The incident X-ray energy can significantly affact the dose. E.g. compared to the dose of 33.2keV for 50mgI/ml, the 32.7keV dose decreases 38%, whereas the dose of 33.7 keV increases 69.2%, and the variation will strengthen more with enhanced IC. The segmented voxel mouse head phantom also showed that the average dose enhancement effect and the maximal voxel dose per photon depends little on the iodine voxel volume ratio, but strongly on IC. Conclusion: To decrease dose damage in SRA, the high-Z contrast agent should be used as little as possible, and try to avoid radiating locally the injected position immediately after the contrast agent injection. The fragile vessel containing iodine should avoid closely irradiating. Avoiding irradiating through the no or thin skull region, or appending thin equivalent material from outside to protect is also a better method. As long as SRA image quality is ensured, using incident X-ray energy as low as possible.« less

Marine Corps Requirements and Procedures for Decontamination and Collective Protection Study. Volume 1.

DTIC Science & Technology

1982-08-01

results of changing selected independent variables. ri The results of the projection of chemical agent density and cloud drift, including dissapation and... combination of agent effects, creates, over time, an extensive threat to wide areas of the FBHA, according to current theories. Shifting wind patterns...will be proposed in paragraph 2.7. The selection of decontamination equipment by the study team is a result of a combination of factors. First, current

Biodegradation of Orthodontic Appliances and Their Effects on the Blood Level of Nickel and Chromium

DTIC Science & Technology

1990-05-01

production of stainless steels and other nickel alloys used for electroplating, battery manufacturing, in catalysts, coins and inorganic pigments . 1...as stainless steel, electroplating as a protective coating on other metals, in catalysts, in pigments , as a tanning agent for leather, textile...the earth’s crust. Titanium is 5 extensively used as a white pigment in paint, plastics and paper, in food as a coloring agent, in cosmetics and

Protection against 2-chloroethyl ethyl sulfide (CEES) - induced cytotoxicity in human keratinocytes by an inducer of the glutathione detoxification pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abel, Erika L.; Bubel, Jennifer D.; Simper, Melissa S.

2011-09-01

Sulfur mustard (SM or mustard gas) was first used as a chemical warfare agent almost 100 years ago. Due to its toxic effects on the eyes, lungs, and skin, and the relative ease with which it may be synthesized, mustard gas remains a potential chemical threat to the present day. SM exposed skin develops fluid filled bullae resulting from potent cytotoxicity of cells lining the basement membrane of the epidermis. Currently, there are no antidotes for SM exposure; therefore, chemopreventive measures for first responders following an SM attack are needed. Glutathione (GSH) is known to have a protective effect againstmore » SM toxicity, and detoxification of SM is believed to occur, in part, via GSH conjugation. Therefore, we screened 6 potential chemopreventive agents for ability to induce GSH synthesis and protect cultured human keratinocytes against the SM analog, 2-chloroethyl ethyl sulfide (CEES). Using NCTC2544 human keratinocytes, we found that both sulforaphane and methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate (CDDO-Me) stimulated nuclear localization of Nrf2 and induced expression of the GSH synthesis gene, GCLM. Additionally, we found that treatment with CDDO-Me elevated reduced GSH content of NCTC2544 cells and preserved their viability by {approx} 3-fold following exposure to CEES. Our data also suggested that CDDO-Me may act additively with 2,6-dithiopurine (DTP), a nucleophilic scavenging agent, to increase the viability of keratinocytes exposed to CEES. These results suggest that CDDO-Me is a promising chemopreventive agent for SM toxicity in the skin. - Highlights: > CDDO-Me treatment increased intracellular GSH in human keratinocytes. > CDDO-Me increased cell viability following exposure to the half-mustard, CEES. > The cytoprotective effect of CDDO-Me was likely due to scavenging with endogenous GSH.« less

Lycopene as A Carotenoid Provides Radioprotectant and Antioxidant Effects by Quenching Radiation-Induced Free Radical Singlet Oxygen: An Overview

PubMed Central

Pirayesh Islamian, Jalil; Mehrali, Habib

2015-01-01

Radio-protectors are agents that protect human cells and tissues from undesirable effects of ionizing radiation by mainly scavenging radiation-induced free radicals. Although chemical radio-protectors diminish these deleterious side effects they induce a number of unwanted effects on humans such as blood pressure modifications, vomiting, nausea, and both local and generalized cutaneous reactions. These disadvantages have led to emphasis on the use of some botanical radio-protectants as alternatives. This review has collected and organized studies on a plant-derived radio-protector, lycopene. Lycopene protects normal tissues and cells by scavenging free radicals. Therefore, treatment of cells with lycopene prior to exposure to an oxidative stress, oxidative molecules or ionizing radiation may be an effective approach in diminishing undesirable effects of radiation byproducts. Studies have designated lycopene to be an effective radio-protector with negligible side effects. PMID:25685729

Effect of Mucuna pruriens Seed Extract Pretreatment on the Responses of Spontaneously Beating Rat Atria and Aortic Ring to Naja sputatrix (Javan Spitting Cobra) Venom

PubMed Central

Fung, Shin Yee; Tan, Nget Hong; Sim, Si Mui; Aguiyi, John C.

2012-01-01

Mucuna pruriens Linn. (velvet bean) has been used by native Nigerians as a prophylactic for snakebite. Rats pretreated with M. pruriens seed extract (MPE) have been shown to protect against the lethal and cardiovascular depressant effects of Naja sputatrix (Javan spitting cobra) venoms, and the protective effect involved immunological neutralization of the venom toxins. To investigate further the mechanism of the protective effect of MPE pretreatment against cobra venom toxicity, the actions of Naja sputatrix venom on spontaneously beating rat atria and aortic rings isolated from both MPE pretreated and untreated rats were studied. Our results showed that the MPE pretreatment conferred protection against cobra venom-induced depression of atrial contractility and atrial rate in the isolated atrial preparations, but it had no effect on the venom-induced contractile response of aortic ring preparation. These observations suggested that the protective effect of MPE pretreatment against cobra venom toxicity involves a direct protective action of MPE on the heart function, in addition to the known immunological neutralization mechanism, and that the protective effect does not involve action on blood vessel contraction. The results also suggest that M. pruriens seed may contain novel cardioprotective agent with potential therapeutic value. PMID:21785646

The evaluation of dentinal tubule occlusion by desensitizing agents: a real-time measurement of dentinal fluid flow rate and scanning electron microscopy.

PubMed

Kim, S Y; Kim, E J; Kim, D S; Lee, I B

2013-01-01

The aims of this study were to examine changes in dentinal fluid flow (DFF) during the application of a desensitizing agent and to compare the permeability reduction levels among different types of desensitizing agents. A cervical cavity was prepared for the exposure of cervical dentin on an extracted human premolar connected to a subnanoliter fluid flow measuring device under 20 cm of water pressure. The cavity was acid-etched with 32% phosphoric acid to make dentin highly permeable. The different types of desensitizing agents that were applied on the cavity were Seal&Protect as the light-curing adhesive type, SuperSeal and BisBlock as oxalate types, Gluma Desensitizer as the protein-precipitation type, and Bi-Fluoride 12 as the fluoride type. DFF was measured from the time before the application of the desensitizing agent throughout the application procedure to five minutes after the application. The characteristics of dentinal tubule occlusion of each desensitizing agent were examined by scanning electron microscopy. The DFF rate after each desensitizing agent application was significantly reduced when compared to the initial DFF rate before application for all of the desensitizing agents (p<0.05). Seal&Protect showed a greater reduction in the DFF rate when compared to Gluma Desensitizer and Bi-Fluoride 12 (p<0.05). SuperSeal and BisBlock exhibited a greater reduction in DFF rate when compared to Bi-Fluoride 12 (p<0.05). The dentin hypersensitivity treatment effects of the employed desensitizing agents in this study were confirmed through real-time measurements of DFF changes. The light-curing adhesive and oxalate types showed greater reduction in the DFF rate than did the protein-precipitation and fluoride types.

Polydopamine-coated capsules

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, Scott R.; Sottos, Nancy R.; Kang, Sen

One aspect of the invention is a polymer material comprising a capsule coated with PDA. In certain embodiments, the capsule encapsulates a functional agent. The encapsulated functional agent may be an indicating agent, healing agent, protecting agent, pharmaceutical drug, food additive, or a combination thereof.

A Diverse Set of Single-domain Antibodies (VHHs) against the Anthrax Toxin Lethal and Edema Factors Provides a Basis for Construction of a Bispecific Agent That Protects against Anthrax Infection*

PubMed Central

Vrentas, Catherine E.; Moayeri, Mahtab; Keefer, Andrea B.; Greaney, Allison J.; Tremblay, Jacqueline; O'Mard, Danielle; Leppla, Stephen H.; Shoemaker, Charles B.

2016-01-01

Infection with Bacillus anthracis, the causative agent of anthrax, can lead to persistence of lethal secreted toxins in the bloodstream, even after antibiotic treatment. VHH single-domain antibodies have been demonstrated to neutralize diverse bacterial toxins both in vitro and in vivo, with protein properties such as small size and high stability that make them attractive therapeutic candidates. Recently, we reported on VHHs with in vivo activity against the protective antigen component of the anthrax toxins. Here, we characterized a new set of 15 VHHs against the anthrax toxins that act by binding to the edema factor (EF) and/or lethal factor (LF) components. Six of these VHHs are cross-reactive against both EF and LF and recognize the N-terminal domain (LFN, EFN) of their target(s) with subnanomolar affinity. The cross-reactive VHHs block binding of EF/LF to the protective antigen C-terminal binding interface, preventing toxin entry into the cell. Another VHH appears to recognize the LF C-terminal domain and exhibits a kinetic effect on substrate cleavage by LF. A subset of the VHHs neutralized against EF and/or LF in murine macrophage assays, and the neutralizing VHHs that were tested improved survival of mice in a spore model of anthrax infection. Finally, a bispecific VNA (VHH-based neutralizing agent) consisting of two linked toxin-neutralizing VHHs, JMN-D10 and JMO-G1, was fully protective against lethal anthrax spore infection in mice as a single dose. This set of VHHs should facilitate development of new therapeutic VNAs and/or diagnostic agents for anthrax. PMID:27539858

A Diverse Set of Single-domain Antibodies (VHHs) against the Anthrax Toxin Lethal and Edema Factors Provides a Basis for Construction of a Bispecific Agent That Protects against Anthrax Infection.

PubMed

Vrentas, Catherine E; Moayeri, Mahtab; Keefer, Andrea B; Greaney, Allison J; Tremblay, Jacqueline; O'Mard, Danielle; Leppla, Stephen H; Shoemaker, Charles B

2016-10-07

Infection with Bacillus anthracis, the causative agent of anthrax, can lead to persistence of lethal secreted toxins in the bloodstream, even after antibiotic treatment. VHH single-domain antibodies have been demonstrated to neutralize diverse bacterial toxins both in vitro and in vivo, with protein properties such as small size and high stability that make them attractive therapeutic candidates. Recently, we reported on VHHs with in vivo activity against the protective antigen component of the anthrax toxins. Here, we characterized a new set of 15 VHHs against the anthrax toxins that act by binding to the edema factor (EF) and/or lethal factor (LF) components. Six of these VHHs are cross-reactive against both EF and LF and recognize the N-terminal domain (LF N , EF N ) of their target(s) with subnanomolar affinity. The cross-reactive VHHs block binding of EF/LF to the protective antigen C-terminal binding interface, preventing toxin entry into the cell. Another VHH appears to recognize the LF C-terminal domain and exhibits a kinetic effect on substrate cleavage by LF. A subset of the VHHs neutralized against EF and/or LF in murine macrophage assays, and the neutralizing VHHs that were tested improved survival of mice in a spore model of anthrax infection. Finally, a bispecific VNA (VHH-based neutralizing agent) consisting of two linked toxin-neutralizing VHHs, JMN-D10 and JMO-G1, was fully protective against lethal anthrax spore infection in mice as a single dose. This set of VHHs should facilitate development of new therapeutic VNAs and/or diagnostic agents for anthrax. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Bee Venom and Its Component Apamin as Neuroprotective Agents in a Parkinson Disease Mouse Model

PubMed Central

Vulinović, Franca; Grünewald, Anne; Chevarin, Caroline; Klein, Christine; Oertel, Wolfgang H.; Hirsch, Etienne C.; Michel, Patrick P.; Hartmann, Andreas

2013-01-01

Bee venom has recently been suggested to possess beneficial effects in the treatment of Parkinson disease (PD). For instance, it has been observed that bilateral acupoint stimulation of lower hind limbs with bee venom was protective in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In particular, a specific component of bee venom, apamin, has previously been shown to have protective effects on dopaminergic neurons in vitro. However, no information regarding a potential protective action of apamin in animal models of PD is available to date. The specific goals of the present study were to (i) establish that the protective effect of bee venom for dopaminergic neurons is not restricted to acupoint stimulation, but can also be observed using a more conventional mode of administration and to (ii) demonstrate that apamin can mimic the protective effects of a bee venom treatment on dopaminergic neurons. Using the chronic mouse model of MPTP/probenecid, we show that bee venom provides sustained protection in an animal model that mimics the chronic degenerative process of PD. Apamin, however, reproduced these protective effects only partially, suggesting that other components of bee venom enhance the protective action of the peptide. PMID:23637888

Comparative analysis of the relative potential of silver, zinc-oxide and titanium-dioxide nanoparticles against UVB-induced DNA damage for the prevention of skin carcinogenesis

PubMed Central

Arora, Sumit; Omar, Yousef; Ijaz, Zohaib Mohammad; AL-Ghadhban, Ahmed; Deshmukh, Sachin K.; Carter, James E.; Singh, Ajay P.; Singh, Seema

2016-01-01

Sunscreen formulations containing UVB filters, such as Zinc-oxide (ZnO) and titanium-dioxide (TiO2) nanoparticles (NPs) have been developed to limit the exposure of human skin to UV-radiations. Unfortunately, these UVB protective agents have failed in controlling the skin cancer incidence. We recently demonstrated that silver nanoparticles (Ag-NPs) could serve as novel protective agents against UVB-radiations. Here our goal was to perform comparative analysis of direct and indirect UVB-protection efficacy of ZnO-, TiO2- and Ag-NPs. Sun-protection-factor calculated based on their UVB-reflective/absorption abilities was the highest for TiO2-NPs followed by Ag- and ZnO-NPs. This was further confirmed by studying indirect protection of UVB radiation-induced death of HaCaT cells. However, only Ag-NPs were active in protecting HaCaT cells against direct UVB-induced DNA-damage by repairing bulky-DNA lesions through nucleotide-excision-repair mechanism. Moreover, Ag-NPs were also effective in protecting HaCaT cells from UVB-induced oxidative DNA damage by enhancing SOD/CAT/GPx activity. In contrast, ZnO- and TiO2-NPs not only failed in providing any direct protection from DNA-damage, but rather enhanced oxidative DNA-damage by increasing ROS production. Together, these findings raise concerns about safety of ZnO- and TiO2-NPs and establish superior protective efficacy of Ag-NPs. PMID:27693632

Cytogenetic studies on Nigella sativa seeds extract and thymoquinone on mouse cells infected with schistosomiasis using karyotyping.

PubMed

Aboul-Ela, Ezzat I

2002-04-26

The protective effect of Nigella sativa seed extract and its main constituents thymoquinone (TQ) was studied on mouse cells infected with schistosomiasis. Bone marrow cells in the in vivo experiments and spleen cells in the in vitro one were used to evaluate the potentially protective effect of these natural compounds on the induction of chromosomal aberrations. Karyotyping of the mice cells illustrated that the main abnormalities were gaps, fragments and deletions especially in chromosomes 2, 6 and some in chromosomes 13 and 14. Both N. sativa extract and TQ were considered as protective agents against the chromosomal aberrations induced as a result of schistosomiasis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walker, E.M. Jr.; Gale, G.R.

Cisplatin, an agent widely used in the chemotherapy of a variety of human malignancies, is often dose-limited owing to its nephrotoxicity. Some of the approaches under consideration, regarding the reduction of cisplatin nephrotoxicity, include the use of hydration and osmotic diuresis, pharmacological diuretics, chelating agents or agents which otherwise react with cisplatin or reverse cisplatin-induced deoxyribonucleic acid cross-links, and antioxidants to destroy free radicals, especially superoxide radicals, produced by cisplatin. The effects of each of these and other interventions on cisplatin-induced nephrotoxicity are delineated, along with their proposed mechanisms and effects on therapeutic efficacy. The current status of development ofmore » organoplatinum analogs yielding congeners with less nephrotoxicity and greater efficacy is discussed briefly. Finally, a possible role of endogenous and/or exogenous prostaglandins in protecting against or reversing heavy metal nephrotoxicity is suggested.« less

Combination chemoprevention: future direction of colorectal cancer prevention.

PubMed

Zhou, Ping; Cheng, Shao-Wen; Yang, Rong; Wang, Bing; Liu, Jian

2012-05-01

Recent research has drawn attention to protective effects of chemopreventive agents that reverse, suppress, or prevent the carcinogenic progression using pharmacological or nutritional agents. Aspirin and celecoxib are the promising preventive agents to effectively reduce the risk of colorectal cancer, but such agents are associated with severe gastrointestinal and cardiovascular side effects in long-term administration at high doses. Recently, the strategy that combinational use with several chemopreventive agents at low doses induces greater inhibition of carcinogenesis has become the focus. The nonsteroidal anti-inflammatory drugs (NSAIDs) may combine with ornithine decarboxylase inhibitors, hydroxymethylglutaryl-CoA reductase inhibitors, epidermal growth factor signaling inhibitors, peroxisome proliferator-activated receptor-γ ligands, and tumor necrosis factor-related apoptosis-inducing ligand, to magnify the chemoprophylactic effect. It is noteworthy that the phase III trial of difluoromethylornithine combination with sulidac has shown greater and effective preventive roles, which pave the way for the use of combinations of other agents. The long-term statins and low-dose NSAIDs have also been associated with risk reduction in vitro, in vivo, and in retrospective studies; however, the data are inconsistent. Epidermal growth factor signaling inhibitors, peroxisome proliferator-activated receptor-γ ligands and tumor necrosis factor-related apoptosis-inducing ligand have been demonstrated to potentiate the preventive effects of NSAIDs in vitro and in vivo, but these combinational regimens have not yet been applied to clinical research. The major goal of this study was to review combination chemoprevention for colorectal cancer by means of combining low doses of potential preventive agents to increase their chemoprophylaxis efficacy and to minimize toxicity.

Potential Cardiovascular and Renal Protective Effects of Vitamin D and Coenzyme Q10 in l-NAME-Induced Hypertensive Rats.

PubMed

Shamardl, Hanan A; El-Ashmony, Sahar M; Kamel, Hala F; Fatani, Sameer H

2017-08-01

Hypertension is one of the primary modifiable risk factors for cardiovascular disease. Adequate vitamin D (vit D) levels have been shown to reduce vascular smooth muscle contraction and to increase arterial compliance, which may be beneficial in hypertension. Further, coenzyme Q10 (COQ10) through its action to lower oxidative stress has been reported to have beneficial effects on hypertension and heart failure. This study examined the possible cardiac and renal protective effects of vit D and COQ10 both separately and in combination with an angiotensin II receptor blocker, valsartan (vals) in l-NAME hypertensive rats. Hypertension was induced in rats by l-NAME administration. Following induction of hypertension, the rats were assigned into the following 6 subgroups: an l-NAME alone group and treated groups receiving the following drugs intraperitoneally for 6 weeks; vals, vit D, COQ10 and combination of vals with either vit D or COQ10. A group of normotensive rats were used as negative controls. At the end of the treatment period, blood pressure, serum creatinine, blood urea nitrogen, lipids and serum, cardiac and renal parameters of oxidative stress were measured. Compared to the l-NAME only group, all treatments lowered systolic, diastolic, mean arterial pressure, total cholesterol, low-density lipoprotein cholesterol, and creatinine levels as well as TNF-α and malondialdehyde. Further, the agents increased serum, cardiac and renal total antioxidant capacity. Interestingly, the combination of agents had further effects on all the parameters compared to treatment with each single agent. The study suggests that the additive protective effects of vit D and COQ10 when used alone or concurrent with vals treatment in hypertensive rats may be due to their effects as antioxidants, anticytokines and blood pressure conservers. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Exposure of U.S. National Parks to land use and climate change 1900-2100

Treesearch

Andrew J. Hansen; Nathan Piekielek; Cory Davis; Jessica Haas; David M. Theobald; John E. Gross; William B. Monahan; Tom Olliff; Steven W. Running

2014-01-01

Many protected areas may not be adequately safeguarding biodiversity from human activities on surrounding lands and global change. The magnitude of such change agents and the sensitivity of ecosystems to these agents vary among protected areas. Thus, there is a need to assess vulnerability across networks of protected areas to determine those most at risk and to lay...

[Decorporation agents for internal radioactive contamination].

PubMed

Ohmachi, Yasushi

2015-01-01

When radionuclides are accidentally ingested or inhaled, blood circulation or tissue/organ deposition of the radionuclides causes systemic or local radiation effects. In such cases, decorporation therapy is used to reduce the health risks due to their intake. Decorporation therapy includes reduction and/or inhibition of absorption from the gastrointestinal tract, isotopic dilution, and the use of diuretics, adsorbents, and chelating agents. For example, penicillamine is recommended as a chelating agent for copper contamination, and diethylene triamine pentaacetic acid is approved for the treatment of internal contamination with plutonium. During chelation therapy, the removal effect of the drugs should be monitored using a whole-body counter and/or bioassay. Some authorities, such as the National Council on Radiation Protection and Measurements and International Atomic Energy Agency, have reported recommended decorporation agents for each radionuclide. However, few drugs are approved by the US Food and Drug Administration, and many are off-label-use agents. Because many decontamination agents are drugs that have been available for a long time and have limited efficacy, the development of new, higher-efficacy drugs has been carried out mainly in the USA and France. In this article, in addition to an outline of decorporation agents for internal radioactive contamination, an outline of our research on decorporation agents for actinide (uranium and plutonium) contamination and for radio-cesium contamination is also presented.

Protective Effect of Pyruvate Against Radiation-Induced Damage in Collagenized Tissues

NASA Technical Reports Server (NTRS)

Griko, Y. V.; Yan, Xiaoli

2016-01-01

Exposure to high doses of ionizing radiation produces both acute and late effects on the collagenized tissues and have profound effects on wound healing. Because of the crucial practical importance for new radioprotective agents, our study has been focused on evaluation of the efficacy of non-toxic naturally occurring compounds to protect tissue integrity against high-dose gamma radiation. Here, we demonstrate that molecular integrity of collagen may serve as a sensitive biological marker for quantitative evaluation of molecular damage to collagenized tissue and efficacy of radioprotective agents. Increasing doses of gamma radiation (0-50kGy) result in progressive destruction of the native collagen fibrils, which provide a structural framework, strength, and proper milieu for the regenerating tissue. The strategy used in this study involved the thermodynamic specification of all structural changes in collagenized matrix of skin, aortic heart valve, and bone tissue induced by different doses and conditions of g-irradiation. This study describes a simple biophysical approach utilizing the Differential Scanning Calorimetry (DSC) to characterize the structural resistance of the aortic valve matrix exposed to different doses of g-irradiation. It allows us to identify the specific response of each constituent as well as to determine the influence of the different treatments on the characteristic parameters of protein structure. We found that pyruvate, a substance that naturally occurs in the body, provide significant protection (up to 80%) from biochemical and biomechanical damage to the collagenized tissue through the effective targeting of reactive oxygen species. The recently discovered role of pyruvate in the cell antioxidant defense to O2 oxidation, and its essential constituency in the daily human diet, indicate that the administration of pyruvate-based radioprotective formulations may provide safe and effective protection from deleterious effects of ionizing radiation.

Optimization of a protective medium for freeze-dried Pichia membranifaciens and application of this biocontrol agent on citrus fruit.

PubMed

Niu, X; Deng, L; Zhou, Y; Wang, W; Yao, S; Zeng, K

2016-07-01

To optimize a protective medium for freeze-dried Pichia membranifaciens and to evaluate biocontrol efficacies of agents against blue and green mould and anthracnose in citrus fruit. Based on the screening assays of saccharides and antioxidants, response surface methodology was used to optimize sucrose, sodium glutamate and skim milk to improve viability of freeze-dried Pi. membranifaciens. Biocontrol assays were conducted between fresh and freeze-dried Pi. membranifaciens against Penicillium italicum, Penicillium digitatum and Colletotrichum gloeosporioides in citrus fruit. Solving the regression equation indicated that the optimal protective medium was 6·06% (w/v) sucrose combined with 3·40% (w/v) sodium glutamate and 5·43% (w/v) skim milk. Pi. membranifaciens freeze-dried in the optimal protective medium showed 76·80% viability, and retained biocontrol efficacy against Pe. italicum, Pe. digitatum and Co. gloeosporioides in citrus fruit. The optimal protective medium showed more effective protective properties than each of the three protectants used alone. The viability of freeze-dried Pi. membranifaciens finally reached 76·80%. Meanwhile, the biocontrol efficacies showed no significant difference between fresh and freeze-dried yeast against Pe. italicum, Pe. digitatum and Co. gloeosporioides in citrus fruit. The results showed the potential value of Pi. membranifaciens CICC 32259 for commercialization. © 2016 The Society for Applied Microbiology.

Stoichiometric and Catalytic Scavengers as Protection Against Nerve Agent Toxicity: A Mini Review

DTIC Science & Technology

2007-01-01

signs of nerve agent toxicity following exposure . Assessments of motor activity , coordination, and acquisition of spatial memory were performed for 2...serious side occur before endogenous AChE is affected (approxi- effects if administered in the absence of cholinesterase mately 2 min after exposure to an...after guinea pigs of cholinesterase in the blood and the level of protec- were administered 60mg/kg of HuBuChE (-󈧎-fold tion against OP poisoning

Efficacy of antidotes (midazolam, atropine and HI-6) on nerve agent induced molecular and neuropathological changes.

PubMed

RamaRao, Golime; Afley, Prachiti; Acharya, Jyothiranjan; Bhattacharya, Bijoy Krishna

2014-04-04

Recent alleged attacks with nerve agent sarin on civilians in Syria indicate their potential threat to both civilian and military population. Acute nerve agent exposure can cause rapid death or leads to multiple and long term neurological effects. The biochemical changes that occur following nerve agent exposure needs to be elucidated to understand the mechanisms behind their long term neurological effects and to design better therapeutic drugs to block their multiple neurotoxic effects. In the present study, we intend to study the efficacy of antidotes comprising of HI-6 (1-[[[4-(aminocarbonyl)-pyridinio]-methoxy]-methyl]-2-[(hydroxyimino) methyl] pyridinium dichloride), atropine and midazolam on soman induced neurodegeneration and the expression of c-Fos, Calpain, and Bax levels in discrete rat brain areas. Therapeutic regime consisting of HI-6 (50 mg/kg, i.m), atropine (10 mg/kg, i.m) and midazolam (5 mg/kg, i.m) protected animals against soman (2×LD50, s.c) lethality completely at 2 h and 80% at 24 h. HI-6 treatment reactivated soman inhibited plasma and RBC cholinesterase up to 40%. Fluoro-Jade B (FJ-B) staining of neurodegenerative neurons showed that soman induced significant necrotic neuronal cell death, which was reduced by this antidotal treatment. Soman increased the expression of neuronal proteins including c-Fos, Bax and Calpain levels in the hippocampus, cerebral cortex and cerebellum regions of the brain. This therapeutic regime also reduced the soman induced Bax, Calpain expression levels to near control levels in the different brain regions studied, except a mild induction of c-Fos expression in the hippocampus. Rats that received antidotal treatment after soman exposure were protected from mortality and showed reduction in the soman induced expression of c-Fos, Bax and Calpain and necrosis. Results highlight the need for timely administration of better antidotes than standard therapy in order to prevent the molecular and biochemical changes and subsequent long term neurological effects induced by nerve agents.

Aspects of tests and assessment of filtering materials used for respiratory protection against bioaerosols. Part I: type of active substance, contact time, microorganism species.

PubMed

Majchrzycka, Katarzyna; Gutarowska, Beata; Brochocka, Agnieszka

2010-01-01

This paper presents the results of a study on antimicrobial activity of polymer filter nonwovens produced by needle-punching or melt-blowing with an addition of disinfecting agents. The first part of the paper discusses how the biocidal activity of nonwovens is a function of the active agent added to the nonwovens, the duration of the contact of microorganisms with nonwovens and the type of microorganisms. The types of fibres and disinfecting agents had a considerable effect on the biocidal activity of nonwovens. The biocidal effect of nonwovens increased with the duration of their contact with microorganisms. Fibre activity differed considerably depending on the species of the microorganism. The microorganisms most sensitive to biocidal activity of the active filter nonwoven were S. aureus, M. flavus and E. coli. There were no biocidal effects on spore-forming bacterium B. subtilis.

Prospects in the development of natural radioprotective therapeutics with anti-cancer properties from the plants of Uttarakhand region of India.

PubMed

Painuli, Sakshi; Kumar, Navin

2016-03-01

Radioprotective agents are substances those reduce the effects of radiation in healthy tissues while maintaining the sensitivity to radiation damage in tumor cells. Due to increased awareness about radioactive substances and their fatal effects on human health, radioprotective agents are now the topic of vivid research. Scavenging of free radicals is the most common mechanism in oncogenesis that plays an important role in protecting tissues from lethal effect of radiation exposure therefore radioprotectors are also good anti-cancer agents. There are numerous studies indicating plant-based therapeutics against cancer and radioprotection. Such plants could be further explored for developing them as promising natural radioprotectors with anti-cancer properties. This review systematically presents information on plants having radioprotective and anti-cancer properties. Copyright © 2016 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

Respiratory and Allergic Health Effects of Dampness, Mold, and Dampness-Related Agents: A Review of the Epidemiologic Evidence

PubMed Central

Mendell, Mark J.; Mirer, Anna G.; Cheung, Kerry; Tong, My; Douwes, Jeroen

2011-01-01

Objectives Many studies have shown consistent associations between evident indoor dampness or mold and respiratory or allergic health effects, but causal links remain unclear. Findings on measured microbiologic factors have received little review. We conducted an updated, comprehensive review on these topics. Data sources We reviewed eligible peer-reviewed epidemiologic studies or quantitative meta-analyses, up to late 2009, on dampness, mold, or other microbiologic agents and respiratory or allergic effects. Data extraction We evaluated evidence for causation or association between qualitative/subjective assessments of dampness or mold (considered together) and specific health outcomes. We separately considered evidence for associations between specific quantitative measurements of microbiologic factors and each health outcome. Data synthesis Evidence from epidemiologic studies and meta-analyses showed indoor dampness or mold to be associated consistently with increased asthma development and exacerbation, current and ever diagnosis of asthma, dyspnea, wheeze, cough, respiratory infections, bronchitis, allergic rhinitis, eczema, and upper respiratory tract symptoms. Associations were found in allergic and nonallergic individuals. Evidence strongly suggested causation of asthma exacerbation in children. Suggestive evidence was available for only a few specific measured microbiologic factors and was in part equivocal, suggesting both adverse and protective associations with health. Conclusions Evident dampness or mold had consistent positive associations with multiple allergic and respiratory effects. Measured microbiologic agents in dust had limited suggestive associations, including both positive and negative associations for some agents. Thus, prevention and remediation of indoor dampness and mold are likely to reduce health risks, but current evidence does not support measuring specific indoor microbiologic factors to guide health-protective actions. PMID:21269928

Chemopreventive effects of Furan-2-yl-3-pyridin-2-yl-propenone against 7,12-dimethylbenz[a]anthracene-inducible genotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hwang, Yong Pil; Han, Eun Hee; Choi, Jae Ho

2008-05-01

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response elementmore » (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase (QR). FPP-3 increased the expression and enzymatic activity of GST and QR. Moreover, FPP-3 increased transcriptional activity of GST and QR. GST and QR induction and Nrf2 translocation by FPP-3 were blocked by the PKC inhibitor Goe6983, and the p38 inhibitor SB203580. These results reflected a partial role of PKC{delta} and p38 signaling in FPP-3-mediated GSTA and QR induction through nuclear translocation of Nrf2. Classically, chemopreventive agents either inhibit CYP metabolizing enzyme or induce phase II detoxifying enzymes. These results suggest that FPP-3 has a potent protective effect against DMBA-induced genotoxicity through modulating phase I and II enzymes and that it has potential as a chemopreventive agent.« less

Limitations and challenges in treatment of acute chemical warfare agent poisoning.

PubMed

Thiermann, Horst; Worek, Franz; Kehe, Kai

2013-12-05

Recent news from Syria on a possible use of chemical warfare agents made the headlines. Furthermore, the motivation of terrorists to cause maximal harm shifts these agents into the public focus. For incidents with mass casualties appropriate medical countermeasures must be available. At present, the most important threats arise from nerve agents and sulfur mustard. At first, self-protection and protection of medical units from contamination is of utmost importance. Volatile nerve agent exposure, e.g. sarin, results in fast development of cholinergic crisis. Immediate clinical diagnosis can be confirmed on-site by assessment of acetylcholinesterase activity. Treatment with autoinjectors that are filled with 2mg atropine and an oxime (at present obidoxime, pralidoxime, TMB-4 or HI-6) are not effective against all nerve agents. A more aggressive atropinisation has to be considered and more effective oximes (if possible with a broad spectrum or a combination of different oximes) as well as alternative strategies to cope with high acetylcholine levels at synaptic sites should be developed. A further gap exists for the treatment of patients with sustained cholinergic crisis that has to be expected after exposure to persistent nerve agents, e.g. VX. The requirement for long-lasting artificial ventilation can be reduced with an oxime therapy that is optimized by using the cholinesterase status for guidance or by measures (e.g. scavengers) that are able to reduce the poison load substantially in the patients. For sulfur mustard poisoning no specific antidote is available until now. Symptomatic measures as used for treatment of burns are recommended together with surgical or laser debridement. Thus, huge amounts of resources are expected to be consumed as wound healing is impaired. Possible depots of sulfur mustard in tissues may aggravate the situation. More basic knowledge is necessary to improve substantially therapeutic options. The use of stem cells may provide a new and promising option. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

[Lack of protection against gentamicin ototoxicity by auditory conditioning with noise].

PubMed

Strose, Alex; Hyppolito, Miguel Ângelo; Colombari, Gleice Cristina; Rossato, Maria; Oliveira, Jose Antônio Aparecido de

2014-01-01

Auditory conditioning consists of the pre-exposure to low levels of a potential harmful agent to protect against a subsequent harmful exposure. To confirm if conditioning with an agent different from that used to cause the trauma can also be effective. This was an experimental study with 17 guinea pigs, divided into three groups: an ototoxic control group (Cont) that received intramuscular administration of gentamicin 160 mg/kg/day for ten consecutive days, but no sound exposure; a sound control group (Sound) that was exposed to 85 dB broadband noise centered at 4 kHz, 30 min each day for ten consecutive days, but received no ototoxic medications; and an experimental group (Expt) that received sound exposure identical to the Sound group and after each noise presentation, received gentamicin similarly to Cont group. The animals were evaluated by distortion product otoacoustic emissions (DPOAEs), brainstem auditory evoked potentials (BAEPs), and scanning electron microscopy. The animals that were conditioned with noise did not show any protective effect compared with the ones that received only the ototoxic gentamicin administration. This lack of protection was observed functionally and morphologically. Conditioning with 85 dB broadband noises, 30 min a day for ten consecutive days does not protect against an ototoxic gentamicin administration of 160 mg/kg/day for ten consecutive days in the guinea pig. Copyright © 2014 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Peri-operative anaesthetic myocardial preconditioning and protection – cellular mechanisms and clinical relevance in cardiac anaesthesia

PubMed Central

Kunst, G; Klein, A A

2015-01-01

Preconditioning has been shown to reduce myocardial damage caused by ischaemia–reperfusion injury peri-operatively. Volatile anaesthetic agents have the potential to provide myocardial protection by anaesthetic preconditioning and, in addition, they also mediate renal and cerebral protection. A number of proof-of-concept trials have confirmed that the experimental evidence can be translated into clinical practice with regard to postoperative markers of myocardial injury; however, this effect has not been ubiquitous. The clinical trials published to date have also been too small to investigate clinical outcome and mortality. Data from recent meta-analyses in cardiac anaesthesia are also not conclusive regarding intra-operative volatile anaesthesia. These inconclusive clinical results have led to great variability currently in the type of anaesthetic agent used during cardiac surgery. This review summarises experimentally proposed mechanisms of anaesthetic preconditioning, and assesses randomised controlled clinical trials in cardiac anaesthesia that have been aimed at translating experimental results into the clinical setting. PMID:25764404

The antiaging activity and cerebral protection of rapamycin at micro-doses.

PubMed

Qi, Haiyan; Su, Feng-Yun; Wan, Shan; Chen, Yongjie; Cheng, Yan-Qiong; Liu, Ai-Jun

2014-11-01

The immunosuppressant drug rapamycin was reported to have an antiaging activity, which was attributed to the TORC1 inhibition that inhibits cell proliferation and increases autophagy. However, rapamycin also exhibits a number of harmful adverse effects. Whether rapamycin can be developed into an antiaging agent remains unclear. We demonstrated that rapamycin at micro-doses (below the TORC1 inhibiting concentration) exhibits a cell-protective activity: (1) It protects cultured neurons against neurotoxin MPP(+) and H2O2. (2) It increases survival time of neuron in culture. (3) It maintains the nonproliferative state of cultured senescent human fibroblasts and prevents cell death induced by telomere dysfunction. (4) In animal models, it decreased the cerebral infarct sizes induced by acute ischemia and dramatically extended the life span of stroke prone spontaneously hypertensive rats (SHR-SPs). We propose that rapamycin at micro-dose can be developed into an antiaging agent with a novel mechanism. © 2014 John Wiley & Sons Ltd.

Crystal Structures of Human Carboxylesterase 1 in Covalent Complexes with the Chemical Warfare Agents Soman and Tabun†,‡

PubMed Central

Fleming, Christopher D.; Edwards, Carol C.; Kirby, Stephen D.; Maxwell, Donald M.; Potter, Philip M.; Cerasoli, Douglas M.; Redinbo, Matthew R.

2008-01-01

The organophosphorus nerve agents sarin, soman, tabun, and VX exert their toxic effects by inhibiting the action of human acetylcholinesterase, a member of the serine hydrolase superfamily of enzymes. The current treatments for nerve agent exposure must be administered quickly to be effective and they often do not eliminate long-term toxic side effects associated with organophosphate poisoning. Thus, there is significant need for effective prophylactic methods to protect at-risk personnel from nerve agent exposure, and protein-based approaches have emerged as promising candidates. We present the 2.7 Å resolution crystal structures of the serine hydrolase human carboxylesterase 1 (hCE1), a broad-spectrum drug metabolism enzyme, in covalent acyl-enzyme intermediate complexes with the chemical weapons soman and tabun. The structures reveal that hCE1 binds stereoselectively to these nerve agents; for example, hCE1 appears to react preferentially with the 104-fold more lethal PS stereoisomer of soman relative to the PR form. In addition, structural features of the hCE1 active site indicate that the enzyme may be resistant to dead-end organophosphate aging reactions that permanently inactivate other serine hydrolases. Taken together, these data provide important structural details toward the goal of engineering hCE1 into an organophosphate hydrolase and protein-based therapeutic for nerve agent exposure. PMID:17407327

Topical efficacy of dimercapto-chelating agents against lewisite-induced skin lesions in SKH-1 hairless mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mouret, Stéphane, E-mail: stephane.mouret@irba.fr; Wartelle, Julien; Emorine, Sandy

2013-10-15

Lewisite is a potent chemical warfare arsenical vesicant that can cause severe skin lesions. Today, lewisite exposure remains possible during demilitarization of old ammunitions and as a result of deliberate use. Although its cutaneous toxicity is not fully elucidated, a specific antidote exists, the British anti-lewisite (BAL, dimercaprol) but it is not without untoward effects. Analogs of BAL, less toxic, have been developed such as meso-2,3-dimercaptosuccinic acid (DMSA) and have been employed for the treatment of heavy metal poisoning. However, efficacy of DMSA against lewisite-induced skin lesions remains to be determined in comparison with BAL. We have thus evaluated inmore » this study the therapeutic efficacy of BAL and DMSA in two administration modes against skin lesions induced by lewisite vapor on SKH-1 hairless mice. Our data demonstrate a strong protective efficacy of topical application of dimercapto-chelating agents in contrast to a subcutaneous administration 1 h after lewisite exposure, with attenuation of wound size, necrosis and impairment of skin barrier function. The histological evaluation also confirms the efficacy of topical application by showing that treatments were effective in reversing lewisite-induced neutrophil infiltration. This protective effect was associated with an epidermal hyperplasia. However, for all the parameters studied, BAL was more effective than DMSA in reducing lewisite-induced skin injury. Together, these findings support the use of a topical form of dimercaprol-chelating agent against lewisite-induced skin lesion within the first hour after exposure to increase the therapeutic management and that BAL, despite its side-effects, should not be abandoned. - Highlights: • Topically applied dimercapto-chelating agents reduce lewisite-induced skin damage. • One topical application of BAL or DMSA is sufficient to reverse lewisite effects. • Topical BAL is more effective than DMSA to counteract lewisite-induced skin damage.« less

Mucosal protective agents prevent exacerbation of NSAID-induced small intestinal lesions caused by antisecretory drugs in rats.

PubMed

Satoh, Hiroshi; Amagase, Kikuko; Takeuchi, Koji

2014-02-01

Antisecretory drugs such as histamine H₂-receptor antagonists and proton pump inhibitors are commonly used for the treatment of upper gastrointestinal mucosal lesions induced by nonsteroidal anti-inflammatory drugs (NSAIDs). However, it has recently been reported that these drugs exacerbate NSAID-induced small intestinal lesions in rats. Unfortunately, there are few effective agents for the treatment of this complication. We examined the effects of mucosal protective agents (MPAs) (misoprostol, irsogladine, and rebamipide) and mucin of porcine stomach on diclofenac-induced intestinal lesions and the exacerbation of the lesions by ranitidine or omeprazole. The effects of the drugs on intestinal motility and mucus distribution/content were also examined. Male Wistar rats (180-220 g) were used. Each drug was administered orally under fed conditions. Diclofenac (1-10 mg/kg) produced multiple lesions in the small intestine dose-dependently. Both ranitidine (30 mg/kg) and omeprazole (100 mg/kg) significantly increased the intestinal lesions induced by low doses (3 and 6 mg/kg) of diclofenac. Misoprostol (0.03-0.3 mg/kg), irsogladine (3-30 mg/kg), and rebamipide (30-300 mg/kg), as well as mucin (30-300 mg/kg) inhibited the formation of intestinal lesions caused by a high dose (10 mg/kg) of diclofenac alone and prevented the exacerbation of diclofenac-induced lesions by antisecretory drugs. Diclofenac (10 mg/kg) markedly increased the intestinal motility and decreased the mucosal mucus, and the decrease of mucus was significantly inhibited by the MPAs. These results indicate the usefulness of the MPAs for the treatment of intestinal lesions induced by NSAIDs alone or by coadministration with antisecretory drugs, and suggest that mucus plays an important role in the protection of intestinal mucosa by the MPAs.

Protecting software agents from malicious hosts using quantum computing

NASA Astrophysics Data System (ADS)

Reisner, John; Donkor, Eric

2000-07-01

We evaluate how quantum computing can be applied to security problems for software agents. Agent-based computing, which merges technological advances in artificial intelligence and mobile computing, is a rapidly growing domain, especially in applications such as electronic commerce, network management, information retrieval, and mission planning. System security is one of the more eminent research areas in agent-based computing, and the specific problem of protecting a mobile agent from a potentially hostile host is one of the most difficult of these challenges. In this work, we describe our agent model, and discuss the capabilities and limitations of classical solutions to the malicious host problem. Quantum computing may be extremely helpful in addressing the limitations of classical solutions to this problem. This paper highlights some of the areas where quantum computing could be applied to agent security.

PRotective Effect on the coronary microcirculation of patients with DIabetes by Clopidogrel or Ticagrelor (PREDICT): study rationale and design. A randomized multicenter clinical trial using intracoronary multimodal physiology.

PubMed

Cerrato, Enrico; Quirós, Alicia; Echavarría-Pinto, Mauro; Mejia-Renteria, Hernan; Aldazabal, Andres; Ryan, Nicola; Gonzalo, Nieves; Jimenez-Quevedo, Pilar; Nombela-Franco, Luis; Salinas, Pablo; Núñez-Gil, Iván J; Rumoroso, José Ramón; Fernández-Ortiz, Antonio; Macaya, Carlos; Escaned, Javier

2017-05-19

In diabetic patients a predisposed coronary microcirculation along with a higher risk of distal particulate embolization during primary percutaneous intervention (PCI) increases the risk of peri-procedural microcirculatory damage. However, new antiplatelet agents, in particular Ticagrelor, may protect the microcirculation through its adenosine-mediated vasodilatory effects. PREDICT is an original, prospective, randomized, multicenter controlled study designed to investigate the protective effect of Ticagrelor on the microcirculation during PCI in patient with diabetes mellitus type 2 or pre-diabetic status. The primary endpoints of this study aim to test (i) the decrease in microcirculatory resistance with antiplatelet therapy (Ticagrelor > Clopidogrel; mechanistic effect) and (ii) the relative microcirculatory protection of Ticagrelor compared to Clopidogrel during PCI (Ticagrelor < Clopidogrel; protective effect). PREDICT will be the first multicentre clinical trial to test the adenosine-mediated vasodilatory effect of Ticagrelor on the microcirculation during PCI in diabetic patients. The results will provide important insights into the prospective beneficial effect of this drug in preventing microvascular impairment related to PCI ( http://www.clinicaltrials.gov No. NCT02698618).

Enterococcus faecalis Responds to Individual Exogenous Fatty Acids Independently of Their Degree of Saturation or Chain Length

PubMed Central

2017-01-01

ABSTRACT Enterococcus faecalis is a commensal of the human gastrointestinal tract that can persist in the external environment and is a leading cause of hospital-acquired infections. Given its diverse habitats, the organism has developed numerous strategies to survive a multitude of environmental conditions. Previous studies have demonstrated that E. faecalis will incorporate fatty acids from bile and serum into its membrane, resulting in an induced tolerance to membrane-damaging agents. To discern whether all fatty acids induce membrane stress protection, we examined how E. faecalis responded to individually supplied fatty acids. E. faecalis readily incorporated fatty acids 14 to 18 carbons in length into its membrane but poorly incorporated fatty acids shorter or longer than this length. Supplementation with saturated fatty acids tended to increase generation time and lead to altered cellular morphology in most cases. Further, exogenously supplied saturated fatty acids did not induce tolerance to the membrane-damaging antibiotic daptomycin. Supplementation with unsaturated fatty acids produced variable growth effects, with some impacting generation time and morphology. Exogenously supplied unsaturated fatty acids that are normally produced by E. faecalis and those that are found in bile or serum could restore growth in the presence of a fatty acid biosynthetic inhibitor. However, only the eukaryote-derived fatty acids oleic acid and linoleic acid provided protection from daptomycin. Thus, exogenous fatty acids do not lead to a common physiological effect on E. faecalis. The organism responds uniquely to each, and only host-derived fatty acids induce membrane protection. IMPORTANCE Enterococcus faecalis is a commonly acquired hospital infectious agent with resistance to many antibiotics, including those that target its cellular membrane. We previously demonstrated that E. faecalis will incorporate fatty acids found in human fluids, like serum, into its cellular membrane, thereby altering its membrane composition. In turn, the organism is better able to survive membrane-damaging agents, including the antibiotic daptomycin. We examined fatty acids commonly found in serum and those normally produced by E. faecalis to determine which fatty acids can induce protection from membrane damage. Supplementation with individual fatty acids produced a myriad of different effects on cellular growth, morphology, and stress response. However, only host-derived unsaturated fatty acids provided stress protection. Future studies are aimed at understanding how these specific fatty acids induce protection from membrane damage. PMID:29079613

Corrosion protection of galvanized steels by silane-based treatments

NASA Astrophysics Data System (ADS)

Yuan, Wei

The possibility of using silane coupling agents as replacements for chromate treatments was investigated on galvanized steel substrates. In order to understand the influence of deposition parameters on silane film formation, pure zinc substrates were first used as a model for galvanized steel to study the interaction between silane coupling agents and zinc surfaces. The silane films formed on pure zinc substrates from aqueous solutions were characterized by ellipsometry, contact angle measurements, reflection absorption infrared spectroscopy, x-ray photoelectron spectroscopy, and atomic force microscopy. The deposition parameters studied include solution concentration, solution dipping time and pH value of the applied solution. It appears that silane film formation involved a true equilibrium of hydrolysis and condensation reactions in aqueous solutions. It has been found that the silane film thickness obtained depends primarily on the solution concentration and is almost independent of the solution dipping time. The molecular orientation of applied silane films is determined by the pH value of applied silane solutions and the isoelectric point of metal substrates. The deposition window in terms of pH value for zinc substrates is between 6.0 and 9.0. The total surface energy of the silane-coated pure zinc substrates decreases with film aging time, the decrease rate, however, is determined by the nature of silane coupling agents. Selected silane coupling agents were applied as prepaint or passivation treatments onto galvanized steel substrates. The corrosion protection provided by these silane-based treatments were evaluated by salt spray test, cyclic corrosion test, electrochemical impedance spectroscopy, and stack test. The results showed that silane coupling agents can possibly be used to replace chromates for corrosion control of galvanized steel substrates. Silane coatings provided by these silane treatments serve mainly as physical barriers. Factors that affect the performance of a silane coupling agent in the application of corrosion control include chemical reactivity, hydrophobic character, siloxane crosslinker network, and film thickness. Good protections afforded by the silane treatments are a synergetic effect of all these factors.

Effects of the calcium channel blocker verapamil and sulphydryl reducing agent dithiothreitol on atractyloside toxicity in precision-cut rat renal cortical and liver slices.

PubMed

Obatomi, D K; Blackburn, R O; Bach, P H

2001-10-01

The effects of dithiothreitol (DTT), a sulfhydryl-containing agent and verapamil (VRP), a calcium channel blocker as possible cytoprotectants against the atractyloside-induced toxicity were characterized in rat kidney and liver slices in vitro using multiple markers of toxicity. Precision-cut slices (200 microM thick) were either incubated with atractyloside (2 mM) or initially preincubated with either DTT (5 mM) or VRP (100 microM) for 30 min followed by exposure to atractyloside (2 mM) for 3 h at 37 degrees C on a rocker platform rotated at approximately 3 rpm. All of the toxicity parameters were sensitive to exposure to atractyloside, but treatment with DTT or VRP alone did not provide any indication of damage to the tissues. Preincubation of slices containing either DTT or VRP for 30 min provided total protection against atractyloside-induced increase in LDH leakage in both kidney and liver slices. Increased induction of lipid peroxidation by atractyloside in liver slices was completely abolished by DTT and VRP. Both DTT and VRP provided partial protection against atractyloside-induced inhibition of gluconeogenesis in both kidney and liver slices. Atractyloside-induced ATP depletion in both kidney and liver slices was partially abolished by VRP but not DTT. The significant depletion of GSH in the kidney slices by atractyloside was completely reversed by DTT only, while VRP alone reversed the same process in liver slices. Decreased MTT reductive capacity and significant increase in ALT leakage caused by atractyloside in liver slices was partially reversed. Complete protection was achieved with both DTT and VRP against atractyloside-induced inhibition of PAH uptake in kidney slices. These findings suggest that both DTT and VRP exert cytoprotective effects in atractyloside-induced biochemical perturbation, effects that differ in liver and kidney. The effect of these agents on atractyloside has provided us with a further understanding of the molecular mechanism of its action.

Co-Selection of Resistance to Antibiotics, Biocides and Heavy Metals, and Its Relevance to Foodborne Pathogens

PubMed Central

Wales, Andrew D.; Davies, Robert H.

2015-01-01

Concerns have been raised in recent years regarding co-selection for antibiotic resistance among bacteria exposed to biocides used as disinfectants, antiseptics and preservatives, and to heavy metals (particularly copper and zinc) used as growth promoters and therapeutic agents for some livestock species. There is indeed experimental and observational evidence that exposure to these non-antibiotic antimicrobial agents can induce or select for bacterial adaptations that result in decreased susceptibility to one or more antibiotics. This may occur via cellular mechanisms that are protective across multiple classes of antimicrobial agents or by selection of genetic determinants for resistance to non-antibiotic agents that are linked to genes for antibiotic resistance. There may also be relevant effects of these antimicrobial agents on bacterial community structure and via non-specific mechanisms such as mobilization of genetic elements or mutagenesis. Notably, some co-selective adaptations have adverse effects on fitness in the absence of a continued selective pressure. The present review examines the evidence for the significance of these phenomena, particularly in respect of bacterial zoonotic agents that commonly occur in livestock and that may be transmitted, directly or via the food chain, to human populations. PMID:27025641

46 CFR 193.15-35 - Enclosure openings.

Code of Federal Regulations, 2014 CFR

2014-10-01

... EQUIPMENT Carbon Dioxide and Clean Agent Extinguishing Systems, Details § 193.15-35 Enclosure openings. (a) Where mechanical ventilation is provided for spaces which are protected by carbon dioxide extinguishing... carbon dioxide extinguishing system, provisions shall be made for easily and effectively closing off the...

46 CFR 193.15-35 - Enclosure openings.

Code of Federal Regulations, 2013 CFR

2013-10-01

... EQUIPMENT Carbon Dioxide and Clean Agent Extinguishing Systems, Details § 193.15-35 Enclosure openings. (a) Where mechanical ventilation is provided for spaces which are protected by carbon dioxide extinguishing... carbon dioxide extinguishing system, provisions shall be made for easily and effectively closing off the...

Concrete deck performance relative to air entrainment.

DOT National Transportation Integrated Search

2009-12-01

Damage to concrete due to freeze-thaw (F-T) action is a serious concern for agencies in cold regions of the United : States. The most effective method to protect concrete from F-T damage is through the addition of an air entraining : agent as an admi...

Skin protection efficacy from UV irradiation and skin penetration property of polysaccharide-benzophenone conjugates as a sunscreen agent.

PubMed

Heo, Sukyoung; Hwang, Hee Sook; Jeong, Yohan; Na, Kun

2018-09-01

Sunscreen materials have been developed to protect skin from UV radiation. However, many organic sunscreen materials are small molecules and absorbed into human skin after topical application and lead to systemic side effects. To improve the adverse effects of conventional sunscreen materials, we designed a sunscreen agent using an organic sunscreen material and a polymer. Dioxybenzone, an organic sunscreen compound is selected and polymerized with natural polymer pullulan. Polymerization not only provides a long polymer backbone to dioxybenzone, but also keeps the distance between benzene rings of the dioxybenzone and prevents reduction of photoabsorption intensity. UV/vis spectrophotometry confirmed that dioxybenzone-pullulan polymer (DOB-PUL) and dioxybenzone (DOB) demonstrated similar UV absorption. To measure the accumulation of sunscreen materials on skin, Franz diffusion cell was used to confirm the accumulation of DOB and lack of penetration of DOB-PUL. Most importantly, DOB showed higher plasma concentration after multiple applications compared to that of DOB-PUL. Copyright © 2018 Elsevier Ltd. All rights reserved.

Protecting Mammalian Hair Cells from Aminoglycoside-Toxicity: Assessing Phenoxybenzamine's Potential.

PubMed

Majumder, Paromita; Moore, Paulette A; Richardson, Guy P; Gale, Jonathan E

2017-01-01

Aminoglycosides (AGs) are widely used antibiotics because of their low cost and high efficacy against gram-negative bacterial infection. However, AGs are ototoxic, causing the death of sensory hair cells in the inner ear. Strategies aimed at developing or discovering agents that protect against aminoglycoside ototoxicity have focused on inhibiting apoptosis or more recently, on preventing antibiotic uptake by the hair cells. Recent screens for ototoprotective compounds using the larval zebrafish lateral line identified phenoxybenzamine as a potential protectant for aminoglycoside-induced hair cell death. Here we used live imaging of FM1-43 uptake as a proxy for aminoglycoside entry, combined with hair-cell death assays to evaluate whether phenoxybenzamine can protect mammalian cochlear hair cells from the deleterious effects of the aminoglycoside antibiotic neomycin. We show that phenoxybenzamine can block FM1-43 entry into mammalian hair cells in a reversible and dose-dependent manner, but pre-incubation is required for maximal inhibition of entry. We observed differential effects of phenoxybenzamine on FM1-43 uptake in the two different types of cochlear hair cell in mammals, the outer hair cells (OHCs) and inner hair cells (IHCs). The requirement for pre-incubation and reversibility suggests an intracellular rather than an extracellular site of action for phenoxybenzamine. We also tested the efficacy of phenoxybenzamine as an otoprotective agent. In mouse cochlear explants the hair cell death resulting from 24 h exposure to neomycin was steeply dose-dependent, with 50% cell death occurring at ~230 μM for both IHC and OHC. We used 250 μM neomycin in subsequent hair-cell death assays. At 100 μM with 1 h pre-incubation, phenoxybenzamine conferred significant protection to both IHCs and OHCs, however at higher concentrations phenoxybenzamine itself showed clear signs of ototoxicity and an additive toxic effect when combined with neomycin. These data do not support the use of phenoxybenzamine as a therapeutic agent in mammalian inner ear. Our findings do share parallels with the observations from the zebrafish lateral line model but they also highlight the necessity for validation in the mammalian system and the potential for differential effects on sensory hair cells from different species, in different systems and even between cells in the same organ.

40 CFR 10.8 - Release.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CLAIMS ACT Procedures § 10.8 Release. Acceptance by the claimant, his agent or legal representative of... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Release. 10.8 Section 10.8 Protection... agent or legal representative and any other person on whose behalf or for whose benefit the claim has...

Protective effects of tea polyphenols and β-carotene against γ-radiation induced mutation and oxidative stress in Drosophila melanogaster.

PubMed

Nagpal, Isha; Abraham, Suresh K

2017-01-01

The commonly consumed antioxidants β-carotene and tea polyphenols were used to assess their protective effects against γ-radiation induced sex-linked recessive lethal (SLRL) mutation and oxidative stress in Drosophila melanogaster . Third instar larvae and adult males of wild-type Oregon-K (ORK) were fed on test agents for 24 and 72 h respectively before exposure to 10Gy γ-irradiation. The treated/control flies were used to assess the induction of SLRLs. We also evaluated antioxidant properties of these phytochemicals in the third instar larvae. Different stages of spermatogenesis in adult males showed a decrease in γ-radiation induced SLRL frequencies upon co-treatment with test agents. A similar trend was observed in larvae. Furthermore, a significant increase in antioxidant enzymatic activities with a decrease in malondialdehyde content was observed. β-carotene and tea polyphenols have exerted antigenotoxic and antioxidant effects in Drosophila . This study demonstrated the suitability of Drosophila as an alternative to mammalian testing for evaluating the antigenotoxic and antioxidant activity of natural products.

Bardoxolone methyl (BARD) ameliorates ischemic AKI and increases expression of protective genes Nrf2, PPARγ, and HO-1

PubMed Central

Wu, Qing Qing; Wang, Yanxia; Senitko, Martin; Meyer, Colin; Wigley, W. Christian; Ferguson, Deborah A.; Grossman, Eric; Chen, Jianlin; Zhou, Xin J.; Hartono, John; Winterberg, Pamela; Chen, Bo; Agarwal, Anapam

2011-01-01

Ischemic acute kidney injury (AKI) triggers expression of adaptive (protective) and maladaptive genes. Agents that increase expression of protective genes should provide a therapeutic benefit. We now report that bardoxolone methyl (BARD) ameliorates ischemic murine AKI as assessed by both renal function and pathology. BARD may exert its beneficial effect by increasing expression of genes previously shown to protect against ischemic AKI, NF-E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor-γ (PPARγ), and heme oxygenase 1 (HO-1). Although we found that BARD alone or ischemia-reperfusion alone increased expression of these genes, the greatest increase occurred after the combination of both ischemia-reperfusion and BARD. BARD had a different mode of action than other agents that regulate PPARγ and Nrf2. Thus we report that BARD regulates PPARγ, not by acting as a ligand but by increasing the amount of PPARγ mRNA and protein. This should increase ligand-independent effects of PPARγ. Similarly, BARD increased Nrf2 mRNA; this increased Nrf2 protein by mechanisms in addition to the prolongation of Nrf2 protein half-life previously reported. Finally, we localized expression of these protective genes after ischemia and BARD treatment. Using double-immunofluorescence staining for CD31 and Nrf2 or PPARγ, we found increased Nrf2 and PPARγ on glomerular endothelia in the cortex; Nrf2 was also present on cortical peritubular capillaries. In contrast, HO-1 was localized to different cells, i.e., tubules and interstitial leukocytes. Although Nrf2-dependent increases in HO-1 have been described, our data suggest that BARD's effects on tubular and leukocyte HO-1 during ischemic AKI may be Nrf2 independent. We also found that BARD ameliorated cisplatin nephrotoxicity. PMID:21289052

Bardoxolone methyl (BARD) ameliorates ischemic AKI and increases expression of protective genes Nrf2, PPARγ, and HO-1.

PubMed

Wu, Qing Qing; Wang, Yanxia; Senitko, Martin; Meyer, Colin; Wigley, W Christian; Ferguson, Deborah A; Grossman, Eric; Chen, Jianlin; Zhou, Xin J; Hartono, John; Winterberg, Pamela; Chen, Bo; Agarwal, Anapam; Lu, Christopher Y

2011-05-01

Ischemic acute kidney injury (AKI) triggers expression of adaptive (protective) and maladaptive genes. Agents that increase expression of protective genes should provide a therapeutic benefit. We now report that bardoxolone methyl (BARD) ameliorates ischemic murine AKI as assessed by both renal function and pathology. BARD may exert its beneficial effect by increasing expression of genes previously shown to protect against ischemic AKI, NF-E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor-γ (PPARγ), and heme oxygenase 1 (HO-1). Although we found that BARD alone or ischemia-reperfusion alone increased expression of these genes, the greatest increase occurred after the combination of both ischemia-reperfusion and BARD. BARD had a different mode of action than other agents that regulate PPARγ and Nrf2. Thus we report that BARD regulates PPARγ, not by acting as a ligand but by increasing the amount of PPARγ mRNA and protein. This should increase ligand-independent effects of PPARγ. Similarly, BARD increased Nrf2 mRNA; this increased Nrf2 protein by mechanisms in addition to the prolongation of Nrf2 protein half-life previously reported. Finally, we localized expression of these protective genes after ischemia and BARD treatment. Using double-immunofluorescence staining for CD31 and Nrf2 or PPARγ, we found increased Nrf2 and PPARγ on glomerular endothelia in the cortex; Nrf2 was also present on cortical peritubular capillaries. In contrast, HO-1 was localized to different cells, i.e., tubules and interstitial leukocytes. Although Nrf2-dependent increases in HO-1 have been described, our data suggest that BARD's effects on tubular and leukocyte HO-1 during ischemic AKI may be Nrf2 independent. We also found that BARD ameliorated cisplatin nephrotoxicity.

Erythropoietin: new approaches to improved molecular designs and therapeutic alternatives.

PubMed

Debeljak, N; Sytkowski, A J

2008-01-01

Erythropoietin (Epo) is a glycoprotein hormone that is the prime regulator of erythropoiesis. Recombinant Epo is a highly effective pharmaceutical used to correct anemias associated with renal insufficiency, cancer and other diseases. Efforts to increase its efficacy in vivo by manipulating the protein's structure have met with some success, and novel Epo-like agents are in development. Additionally, efforts to create Epo mimetic agents are underway, as is the design of agents to increase endogenous production. Because Epo has tissue protective actions outside of erythropoiesis, other designs have focused on producing erythropoietically inactive molecules that still retain extra-hematopoietic activity. The demonstration that Epo can trigger signaling in some cancer cells with, potentially, adverse effects on patient health has raised warning signs in the medical community and has gained the attention of regulatory authorities.

Utilization of Fc Receptors as a Mucosal Vaccine Strategy against an Intracellular Bacterium, Francisella tularensis1

PubMed Central

Rawool, Deepak B.; Bitsaktsis, Constantine; Li, Ying; Gosselin, Diane R.; Lin, Yili; Kurkure, Nitin V.; Metzger, Dennis W.; Gosselin, Edmund J.

2013-01-01

Numerous studies have demonstrated that targeting Ag to Fc receptors (FcR) on APCs can enhance humoral and cellular immunity. However, studies are lacking that examine both the use of FcR-targeting in generating immune protection against infectious agents and the use of FcRs in the induction of mucosal immunity. Francisella tularensis is a category A intracellular mucosal pathogen. Thus, intense efforts are underway to develop a vaccine against this organism. We hypothesized that protection against mucosal infection with F. tularensis would be significantly enhanced by targeting inactivated F. tularensis live vaccine strain (iFt) to FcRs at mucosal sites, via intranasal immunization with mAb-iFt complexes. These studies demonstrate for the first time that: 1) FcR-targeted immunogen enhances immunogen-specific IgA production and protection against subsequent infection in an IgA-dependent manner, 2) FcγR and neonatal FcR are crucial to this protection, and 3) inactivated F. tularensis, when targeted to FcRs, enhances protection against the highly virulent SchuS4 strain of F. tularensis, a category A biothreat agent. In summary, these studies show for the first time the use of FcRs as a highly effective vaccination strategy against a highly virulent mucosal intracellular pathogen. PMID:18390739

Effects of neuroactive steroids on cochlear hair cell death induced by gentamicin.

PubMed

Nakamagoe, Mariko; Tabuchi, Keiji; Nishimura, Bungo; Hara, Akira

2011-12-11

As neuroactive steroids, sex steroid hormones have non-reproductive effects. We previously reported that 17β-estradiol (βE2) had protective effects against gentamicin (GM) ototoxicity in the cochlea. In the present study, we examined whether the protective action of βE2 on GM ototoxicity is mediated by the estrogen receptor (ER) and whether other estrogens (17α-estradiol (αE2), estrone (E1), and estriol (E3)) and other neuroactive steroids, dehydroepiandrosterone (DHEA) and progesterone (P), have similar protective effects. The basal turn of the organ of Corti was dissected from Sprague-Dawley rats and cultured in a medium containing 100 μM GM for 48h. The effects of βE2 and ICI 182,780, a selective ER antagonist, were examined. In addition, the effects of other estrogens, DHEA and P were tested using this culture system. Loss of outer hair cells induced by GM exposure was compared among groups. βE2 exhibited a protective effect against GM ototoxicity, but its protective effect was antagonized by ICI 182,780. αE2, E1, and E3 also protected hair cells against gentamicin ototoxicity. DHEA showed a protective effect; however, the addition of ICI 182,780 did not affect hair cell loss. P did not have any effect on GM-induced outer hair cell death. The present findings suggest that estrogens and DHEA are protective agents against GM ototoxicity. The results of the ER antagonist study also suggest that the protective action of βE2 is mediated via ER but that of DHEA is not related to its conversion to estrogen and binding to ER. Further studies on neuroactive steroids may lead to new insights regarding cochlear protection. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparative analysis of the relative potential of silver, Zinc-oxide and titanium-dioxide nanoparticles against UVB-induced DNA damage for the prevention of skin carcinogenesis.

PubMed

Tyagi, Nikhil; Srivastava, Sanjeev K; Arora, Sumit; Omar, Yousef; Ijaz, Zohaib Mohammad; Al-Ghadhban, Ahmed; Deshmukh, Sachin K; Carter, James E; Singh, Ajay P; Singh, Seema

2016-12-01

Sunscreen formulations containing UVB filters, such as Zinc-oxide (ZnO) and titanium-dioxide (TiO 2 ) nanoparticles (NPs) have been developed to limit the exposure of human skin to UV-radiations. Unfortunately, these UVB protective agents have failed in controlling the skin cancer incidence. We recently demonstrated that silver nanoparticles (Ag-NPs) could serve as novel protective agents against UVB-radiations. Here our goal was to perform comparative analysis of direct and indirect UVB-protection efficacy of ZnO-, TiO 2 - and Ag-NPs. Sun-protection-factor calculated based on their UVB-reflective/absorption abilities was the highest for TiO 2 -NPs followed by Ag- and ZnO-NPs. This was further confirmed by studying indirect protection of UVB radiation-induced death of HaCaT cells. However, only Ag-NPs were active in protecting HaCaT cells against direct UVB-induced DNA-damage by repairing bulky-DNA lesions through nucleotide-excision-repair mechanism. Moreover, Ag-NPs were also effective in protecting HaCaT cells from UVB-induced oxidative DNA damage by enhancing SOD/CAT/GPx activity. In contrast, ZnO- and TiO 2 -NPs not only failed in providing any direct protection from DNA-damage, but rather enhanced oxidative DNA-damage by increasing ROS production. Together, these findings raise concerns about safety of ZnO- and TiO 2 -NPs and establish superior protective efficacy of Ag-NPs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

New phytopharmaceutical agent CJ-20001 modulates stress-induced inflammatory infiltration into gastric mucosa.

PubMed

Yeo, Marie; Kim, Dong-Kyu; Cho, Sung Won; Lee, Song-Jin; Cho, Il-Hwan; Song, Geun-Seog; Moon, Byoung-Seok

2012-05-01

CJ-20001 is a phytopharmaceutical agent and currently being investigated in a Phase II trial for the treatment of acute and chronic gastritis patients in Korea. In this study we addressed the protective effects of CJ-20001 against water immersion restraint stress (WIRS)-induced gastric injury in rats and studied the underlying mechanisms. To evaluate the protective effect of CJ-20001 on stress-induced gastric lesions, rats were exposed to water immersion restraint stress. Inflammatory infiltration into gastric mucosa was examined by immunohistochemistry and in vitro invasion assay. Expression of proinflammatory cytokines was detected with reverse transcription-polymerase chain reaction (RT-PCR). Pretreatment with CJ-20001 dose-dependently attenuated the WIRS-induced gastric lesions as demonstrated by gross pathology and histology. WIRS increased infiltration of mast cells and macrophages into the gastric mucosa and submucosal layer, whereas the inflammatory infiltration was markedly inhibited by CJ-20001 administration. An in vitro cell invasion assay showed that treatment with CJ-20001 decreased the migration of macrophages. CJ-20001 suppressed the expression of proinflammatory cytokines, IL-18, IP-10 and GRO/KC, in lipopolysaccharides (LPS)-treated macrophages. These data suggest that novel phytopharmaceutical agent CJ-20001 has the potent anti-inflammatory properties through inhibition of inflammatory infiltration in psycho-physiological stress-induced gastric injury.

46 CFR 193.15-50 - Clean agent systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... PROTECTION EQUIPMENT Carbon Dioxide and Clean Agent Extinguishing Systems, Details § 193.15-50 Clean agent... carbon dioxide fire extinguishing system. [USCG-2006-24797, 77 FR 33893, June 7, 2012] ...

46 CFR 193.15-50 - Clean agent systems.

Code of Federal Regulations, 2014 CFR

2014-10-01

... PROTECTION EQUIPMENT Carbon Dioxide and Clean Agent Extinguishing Systems, Details § 193.15-50 Clean agent... carbon dioxide fire extinguishing system. [USCG-2006-24797, 77 FR 33893, June 7, 2012] ...

Dunnione protects against experimental cisplatin-induced nephrotoxicity by modulating NQO1 and NAD+ levels.

PubMed

Nazari Soltan Ahmad, Saeed; Rashtchizadeh, Nadereh; Argani, Hassan; Roshangar, Leila; Ghorbani Haghjo, Amir; Sanajou, Davoud; Panah, Fatemeh; Ashrafi Jigheh, Zahra; Dastmalchi, Siavoush; Mesgari-Abbasi, Mehran

2018-06-04

Despite being an efficacious anticancer agent, the clinical utility of cisplatin is hindered by its cardinal side effects. This investigation aimed to appraise potential protective impact of dunnione, a natural naphthoquinone pigment with established NQO1 stimulatory effects, on cisplatin nephrotoxicity of rats. Dunnione was administered orally at 10 and 20 mg/kg doses for 4 d and a single injection of cisplatin was delivered at the second day. Renal histopathology, inflammatory/oxidative stress/apoptotic markers, kidney function, and urinary markers of renal injury were assessed. Dunnione repressed cisplatin-induced inflammation in the kidneys as indicated by decreased TNF-α/IL-1β levels, and reduced nuclear phosphorylated NF-κB p65. This agent also obviated cisplatin-invoked oxidative stress as elucidated by decreased MDA/GSH levels and increased SOD/CAT activities. Dunnione, furthermore, improved renal histological deteriorations as well as caspase-3 activities and terminal deoxynucleotidyl transferase (TUNEL) positive cells, the indicators of apoptosis. Moreover, it up-regulated nuclear Nrf2 and cytosolic haeme-oxygenase-1 (HO-1) and NQO1 levels; meanwhile, promoted NAD + /NADH ratios followed by enhancing the activities of Sirt1 and PARP1; and further attenuated nuclear acetylated NF-κB p65. Dunnione additionally declined cisplatin-evoked retrogression in renal function and upraise in urinary markers of glomerular and tubular injury as demonstrated by decreased serum urea and creatinine with simultaneous reductions in urinary excretions of collagen type IV, podocin, cystatin C, and retinol-binding protein (RBP). Altogether, these findings offer dunnione as a potential protective agent against cisplatin-induced nephrotoxicity in rats.

Gastric anti-ulcer and cytoprotective effect of selenium in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parmar, N.S.; Tariq, M.; Ageel, A.M.

1988-01-01

Selenium, a trace element, in the form of sodium selenite has been studied for its ability to protect the gastric mucosa against the injuries caused by hypothermic restraint stress, aspirin, indomethacin, reserpine, dimaprit, and various other gastric mucosal-damaging (necrotizing) agents in rats. The results demonstrate that oral administration of sodium selenite produces a significant inhibition of the gastric mucosal damage induced by all the procedures used in this study. Selenium, in a nonantisecretory dose, produced a marked cytoprotective effect against all the necrotizing agents. The cytoprotective effect of selenium against the effects of 80% ethanol and 0.6 M HCl wasmore » significantly reversed by prior treatment with a dose of indomethacin that inhibits prostaglandin biosynthesis. These data indicate that sodium selenite inhibits the formation of these lesions by the mucosal generation of prostaglandins. The concentrations of nonprotein sulfhydryls (NP-SH) were significantly decreased in the gastric mucosa following the administration of necrotizing agents--80% ethanol and 0.6 M HCl. Treatment with sodium selenite, which significantly reduced the intensity of gastric lesions, did not replenish the reduced levels of gastric mucosal NP-SH, thus ruling out the mediation of its protective effect through sulfhydryls. The antisecretory effect of sodium selenite, which becomes evident only in the high dose of 20 mumol/kg, may be responsible for the inhibition of gastric lesions induced by aspirin, indomethacin, reserpine, and dimaprit. Our findings show that selenium possesses significant anti-ulcer and adaptive cytoprotective effects. However, further detailed studies are required to confirm these effects, to establish its mechanism(s) of action, and to determine its role in the prophylaxis and treatment of peptic ulcer disease.« less

Perturbational Metabolic Profiling of Human Breast Cancer Cells

EPA Science Inventory

A major goal of toxicity testing is to obtain toxicity data for protecting public health and the environment from adverse effects that may be caused by exposure to environmental agents in the air, water, soil and food. The current toxicological studies that target human health ef...

Developments in Decontamination Technologies of Military Personnel and Equipment

NASA Astrophysics Data System (ADS)

Sata, Utkarsh R.; Ramkumar, Seshadri S.

Individual protection is important for warfighters, first responders and civilians to meet the current threat of toxic chemicals and chemical warfare (CW) agents. Within the realm of individual protection, decontamination of warfare agents is not only required on the battlefield but also in laboratory, pilot plants, production and agent destruction sites. It is of high importance to evaluate various decontaminants and decontamination techniques for implementing the best practices in varying scenarios such as decontamination of personnel, sites and sensitive equipment.

Method for vacuum pressing electrochemical cell components

NASA Technical Reports Server (NTRS)

Andrews, Craig C. (Inventor); Murphy, Oliver J. (Inventor)

2004-01-01

Assembling electrochemical cell components using a bonding agent comprising aligning components of the electrochemical cell, applying a bonding agent between the components to bond the components together, placing the components within a container that is essentially a pliable bag, and drawing a vacuum within the bag, wherein the bag conforms to the shape of the components from the pressure outside the bag, thereby holding the components securely in place. The vacuum is passively maintained until the adhesive has cured and the components are securely bonded. The bonding agent used to bond the components of the electrochemical cell may be distributed to the bonding surface from distribution channels in the components. To prevent contamination with bonding agent, some areas may be treated to produce regions of preferred adhesive distribution and protected regions. Treatments may include polishing, etching, coating and providing protective grooves between the bonding surfaces and the protected regions.

Monitoring to Protect the Character of Individual Wildernesses

Treesearch

David N. Cole

2006-01-01

A primary goal of wilderness stewardship is to protect individual wilderness areas from most anthropogenic change. Numerous agents of change threaten to degrade wilderness character. These agents of change are both internal (for example, grazing) and external (for example, polluting industries) to wilderness. They can be activities (for example, recreation use) or the...

Anti-foot-and-mouth disease virus effects of Chinese herbal kombucha in vivo.

PubMed

Fu, Naifang; Wu, Juncai; Lv, Lv; He, Jijun; Jiang, Shengjun

2015-01-01

The foot and mouth disease virus (FMDV) is sensitive to acids and can be inactivated by exposure to low pH conditions. Spraying animals at risk of infection with suspensions of acid-forming microorganisms has been identified as a potential strategy for preventing FMD. Kombucha is one of the most strongly acid-forming symbiotic probiotics and could thus be an effective agent with which to implement this strategy. Moreover, certain Chinese herbal extracts are known to have broad-spectrum antiviral effects. Chinese herbal kombucha can be prepared by fermenting Chinese herbal extracts with a kombucha culture. Previous studies demonstrated that Chinese herbal kombucha prepared in this way efficiently inhibits FMDV replication in vitro. To assess the inhibitory effects of Chinese herbal kombucha against FMDV in vitro, swine challenged by intramuscular injection with 1000 SID50 of swine FMDV serotype O strain O/China/99 after treatment with Chinese herbal kombucha were partially protected against infection, as demonstrated by a lack of clinical symptoms and qRT-PCR analysis. In a large scale field trial, spraying cattle in an FMD outbreak zone with kombucha protected against infection. Chinese herbal kombucha may be a useful probiotic agent for managing FMD outbreaks.

Anti-foot-and-mouth disease virus effects of Chinese herbal kombucha in vivo

PubMed Central

Fu, Naifang; Wu, Juncai; Lv, Lv; He, Jijun; Jiang, Shengjun

2015-01-01

Abstract The foot and mouth disease virus (FMDV) is sensitive to acids and can be inactivated by exposure to low pH conditions. Spraying animals at risk of infection with suspensions of acid-forming microorganisms has been identified as a potential strategy for preventing FMD. Kombucha is one of the most strongly acid-forming symbiotic probiotics and could thus be an effective agent with which to implement this strategy. Moreover, certain Chinese herbal extracts are known to have broad-spectrum antiviral effects. Chinese herbal kombucha can be prepared by fermenting Chinese herbal extracts with a kombucha culture. Previous studies demonstrated that Chinese herbal kombucha prepared in this way efficiently inhibits FMDV replication in vitro. To assess the inhibitory effects of Chinese herbal kombucha against FMDV in vitro, swine challenged by intramuscular injection with 1000 SID50 of swine FMDV serotype O strain O/China/99 after treatment with Chinese herbal kombucha were partially protected against infection, as demonstrated by a lack of clinical symptoms and qRT-PCR analysis. In a large scale field trial, spraying cattle in an FMD outbreak zone with kombucha protected against infection. Chinese herbal kombucha may be a useful probiotic agent for managing FMD outbreaks. PMID:26691487

Lack of genotoxicity in medical oncology nurses handling antineoplastic drugs: effect of work environment and protective equipment.

PubMed

Gulten, Tuna; Evke, Elif; Ercan, Ilker; Evrensel, Turkkan; Kurt, Ender; Manavoglu, Osman

2011-01-01

In this study we aimed to investigate the genotoxic effects of antineoplastic agents in occupationally exposed oncology nurses. Genotoxic effects mean the disruptive effects in the integrity of DNA and they are associated with cancer development. Biomonitoring of health care workers handling antineoplastic agents is helpful for the evaluation of exposure to cytostatics. The study included an exposed and two control groups. The exposed group (n=9) was comprised of oncology nurses. The first (n=9) and second (n=10) control groups were comprised of subjects who did not come into contact with antineoplastic drugs working respectively in the same department with oncology nurses and in different departments. Genotoxicity evaluation was performed using SCE analysis. After applying culture, harvest and chromosome staining procedures, a total of 25 metaphases were analyzed per person. Kruskal Wallis test was used to perform statistical analysis. A statistically significant difference of sister chromatid exchange frequencies was not observed between the exposed and control groups. Lack of genotoxicity in medical oncology nurses might be due to good working conditions with high standards of technical equipment and improved personal protection.

Memory T cells maintain protracted protection against malaria.

PubMed

Krzych, Urszula; Zarling, Stasya; Pichugin, Alexander

2014-10-01

Immunologic memory is one of the cardinal features of antigen-specific immune responses, and the persistence of memory cells contributes to prophylactic immunizations against infectious agents. Adequately maintained memory T and B cell pools assure a fast, effective and specific response against re-infections. However, many aspects of immunologic memory are still poorly understood, particularly immunologic memory inducible by parasites, for example, Plasmodium spp., the causative agents of malaria. For example, memory responses to Plasmodium antigens amongst residents of malaria endemic areas appear to be either inadequately developed or maintained, because persons who survive episodes of childhood malaria remain vulnerable to intermittent malaria infections. By contrast, multiple exposures of humans and laboratory rodents to radiation-attenuated Plasmodium sporozoites (γ-spz) induce sterile and long-lasting protection against experimental sporozoite challenge. Multifactorial immune mechanisms maintain this protracted and sterile protection. While the presence of memory CD4 T cell subsets has been associated with lasting protection in humans exposed to multiple bites from Anopheles mosquitoes infected with attenuated Plasmodium falciparum, memory CD8 T cells maintain protection induced with Plasmodium yoelii and Plasmodium berghei γ-spz in murine models. In this review, we discuss our observations that show memory CD8 T cells specific for antigens expressed by P. berghei liver stage parasites as an indispensable component for the maintenance of protracted protective immunity against experimental malaria infection; moreover, the provision of an Ag-depot assures a quick recall of memory T cells as IFN-γ-producing effector CD8 T cells and IL-4- producing CD4 T cells that collaborate with B cells for an effective antibody response. Published by Elsevier B.V.

14 CFR 29.1197 - Fire extinguishing agents.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Fire extinguishing agents. 29.1197 Section... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Powerplant Powerplant Fire Protection § 29.1197 Fire extinguishing agents. (a) Fire extinguishing agents must— (1) Be capable of extinguishing flames emanating from...

Protection of Mobile Agents Execution Using a Modified Self-Validating Branch-Based Software Watermarking with External Sentinel

NASA Astrophysics Data System (ADS)

Tomàs-Buliart, Joan; Fernández, Marcel; Soriano, Miguel

Critical infrastructures are usually controlled by software entities. To monitor the well-function of these entities, a solution based in the use of mobile agents is proposed. Some proposals to detect modifications of mobile agents, as digital signature of code, exist but they are oriented to protect software against modification or to verify that an agent have been executed correctly. The aim of our proposal is to guarantee that the software is being executed correctly by a non trusted host. The way proposed to achieve this objective is by the improvement of the Self-Validating Branch-Based Software Watermarking by Myles et al.. The proposed modification is the incorporation of an external element called sentinel which controls branch targets. This technique applied in mobile agents can guarantee the correct operation of an agent or, at least, can detect suspicious behaviours of a malicious host during the execution of the agent instead of detecting when the execution of the agent have finished.

Fibrous Filter to Protect Building Environments from Polluting Agents: A Review

NASA Astrophysics Data System (ADS)

Chavhan, Md. Vaseem; Mukhopadhyay, Arunangshu

2016-04-01

This paper discusses the use of fibrous filter to protect the building environments from air born polluting agents and especially of concern chemical, biological and radiological agents. Air-filtration includes removal of particulate from air and toxic gases from air. In air filtration, particulate which are mostly biological and radioactive types of agents can be removed by using mechanical and electrostatic filters. Some biological agents, which cannot be removed by air filtration alone, special techniques like antimicrobial finish, UV germicides, coated filters etc. are required. Biocide agent can be added into the fibre itself by grafting reaction to impart antimicrobial activity. Chemical agents like toxic gases can be removed by integrating adsorbents and sorbents in filters or by fibre modifications. It is also possible to impart catalytic conversion properties into the fibre to remove volatile gasous. Radioactive agents can be removed by particulate filter if present in the form of aerosol or by gas cleaning by the use of specific fibre impregnate.

Particulate delivery systems for biodefense subunit vaccines.

PubMed

Bramwell, Vincent W; Eyles, Jim E; Oya Alpar, H

2005-06-17

Expanding identification of potentially protective subunit antigens and correlates of protection has provided a basis for the introduction of safer vaccines. Despite encouraging results in animal models, the significant potential of particulate delivery systems in vaccine design has not yet translated into effective vaccines available for use in humans. This review article will focus on the current status of the development of particulate vaccines, mainly liposomes and bio-degradable polymers, against potential agents for biowarfare: plague, anthrax, botulinum, and smallpox; and filoviruses: Marburg and Ebola.

Synthesis and evaluation of novel caged DNA alkylating agents bearing 3,4-epoxypiperidine structure.

PubMed

Kawada, Yuji; Kodama, Tetsuya; Miyashita, Kazuyuki; Imanishi, Takeshi; Obika, Satoshi

2012-07-14

Previously, we reported that the 3,4-epoxypiperidine structure, whose design was based on the active site of DNA alkylating antitumor antibiotics, azinomycins A and B, possesses prominent DNA cleavage activity. In this report, novel caged DNA alkylating agents, which were designed to be activated by UV irradiation, were synthesized by the introduction of four photo-labile protecting groups to a 3,4-epoxypiperidine derivative. The DNA cleavage activity and cytotoxicity of the caged DNA alkylating agents were examined under UV irradiation. Four caged DNA alkylating agents showed various degrees of bioactivity depending on the photosensitivity of the protecting groups.

RRx-001: a systemically non-toxic M2-to-M1 macrophage stimulating and prosensitizing agent in Phase II clinical trials.

PubMed

Oronsky, Bryan; Paulmurugan, Ramasamy; Foygel, Kira; Scicinski, Jan; Knox, Susan J; Peehl, Donna; Zhao, Hongjuan; Ning, Shoucheng; Cabrales, Pedro; Summers, Thomas A; Reid, Tony R; Fitch, William L; Kim, Michelle M; Trepel, Jane B; Lee, Min-Jung; Kesari, Santosh; Abrouk, Nacer D; Day, Regina M; Oronsky, Arnold; Ray, Carolyn M; Carter, Corey A

2017-01-01

According to Hanahan and Weinberg, cancer manifests as six essential physiologic hallmarks: (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) invasion and metastasis. As a facilitator of these traits as well as immunosuppression and chemoresistance, the presence of tumor-associated macrophages (TAMs) may serve as the seventh hallmark of cancer. Anticancer agents that successfully reprogram TAMs to target rather than support tumor cells may hold the key to better therapeutic outcomes. Areas covered: This article summarizes the characteristics of the macrophage-stimulating agent RRx-001, a molecular iconoclast, sourced from the aerospace industry, with a particular emphasis on the cell-to-cell transfer mechanism of action (RBCs to TAMs) underlying its antitumor activity as well as its chemo and radioprotective properties, consolidated from various preclinical and clinical studies. Expert opinion: RRx-001 is macrophage-stimulating agent with the potential to synergize with chemotherapy, radiotherapy and immunotherapy while simultaneously protecting normal tissues from their cytotoxic effects. Given the promising indications of activity in multiple tumor types and these normal tissue protective properties, RRx-001 may be used to treat a broad spectrum of malignancies, if it is approved in the future.

Ancient Chinese Formula Qiong-Yu-Gao Protects Against Cisplatin-Induced Nephrotoxicity Without Reducing Anti-tumor Activity

PubMed Central

Teng, Zhi-Ying; Cheng, Xiao-Lan; Cai, Xue-Ting; Yang, Yang; Sun, Xiao-Yan; Xu, Jin-Di; Lu, Wu-Guang; Chen, Jiao; Hu, Chun-Ping; Zhou, Qian; Wang, Xiao-Ning; Li, Song-Lin; Cao, Peng

2015-01-01

Cisplatin is a highly effective anti-cancer chemotherapeutic agent; however, its clinical use is severely limited by serious side effects, of which nephrotoxicity is the most important. In this study, we investigated whether Qiong-Yu-Gao (QYG), a popular traditional Chinese medicinal formula described 840 years ago, exhibits protective effects against cisplatin-induced renal toxicity. Using a mouse model of cisplatin-induced renal dysfunction, we observed that pretreatment with QYG attenuated cisplatin-induced elevations in blood urea nitrogen and creatinine levels, ameliorated renal tubular lesions, reduced apoptosis, and accelerated tubular cell regeneration. Cisplatin-mediated elevations in tumor necrosis factor alpha (TNF-α) mRNA, interleukin-1 beta (IL-1β) mRNA, and cyclooxygenase-2 (COX-2) protein in the kidney were also significantly suppressed by QYG treatment. Furthermore, QYG reduced platinum accumulation in the kidney by decreasing the expression of copper transporter 1 and organic cation transporter 2. An in vivo study using implanted Lewis lung cancer cells revealed that concurrent administration of QYG and cisplatin did not alter the anti-tumor activity of cisplatin. Our findings suggest that the traditional Chinese medicinal formula QYG inhibits cisplatin toxicity by several mechanisms that act simultaneously, without compromising its therapeutic efficacy. Therefore, QYG may be useful in the clinic as a protective agent to prevent cisplatin-induced nephrotoxicity. PMID:26510880

A Novel Synthesized Sulfonamido-Based Gallate—JEZ-C as Potential Therapeutic Agents for Osteoarthritis

PubMed Central

Lin, Xiao; Lin, Cuiwu; Liu, Buming; Zheng, Li; Zhao, Jinmin

2015-01-01

Gallic acid (GA) and its derivatives are anti-inflammatory agents reported to have an effect on osteoarthritis (OA). However, GA has much weaker anti-oxidant effects and inferior bioactivity compared with its derivatives. We modified GA with the introduction of sulfonamide to synthesize a novel compound named JEZ-C and analyzed its anti-arthritis and chondro-protective effects. Comparison of JEZ-C with its sources i.e. GA and Sulfamethoxazole (SMZ) was also performed. Results showed that JEZ-C could effectively inhibit the IL-1-mediated induction of MMP-1 and MMP-13 and could induce the expression of TIMP-1, which demonstrated its ability to reduce the progression of OA. JEZ-C can also exert chondro-protective effects by promoting cell proliferation and maintaining the phenotype of articular chondrocytes, as evidenced by improved cell growth, enhanced synthesis of cartilage specific markers such as aggrecan, collagen II and Sox9. Meanwhile, expression of the collagen I gene was effectively downregulated, revealing the inhibition of chondrocytes dedifferentiation by JEZ-C. Hypertrophy that may lead to chondrocyte ossification was also undetectable in JEZ-C groups. The recommended dose of JEZ-C ranges from 6.25×10-7 μg/ml to 6.25×10-5 μg/ml, among which the most profound response was observed with 6.25×10-6 μg/ml. In contrast, its source products of GA and SMZ have a weak effect not only in the inhibition of OA but also in the bioactivity of chondrocytes, which indicated the significance of this modification. This study revealed JEZ-C as a promising novel agent in the treatment of chondral and osteochondral lesions. PMID:26107568

Investigation of X-ray permeability of surgical gloves coated with different contrast agents

PubMed Central

Kayan, Mustafa; Yaşar, Selçuk; Saygın, Mustafa; Yılmaz, Ömer; Aktaş, Aykut Recep; Kayan, Fatmanur; Türker, Yasin; Çetinkaya, Gürsel

2016-01-01

Objective: We aimed to investigate the effectiveness and radiation protection capability of latex gloves coated with various contrast agents as an alternative to lead gloves. Methods: The following six groups were created to evaluate the permeability of X-ray in this experimental study: lead gloves, two different non-ionic contrast media (iopromide 370/100 mg I/mL and iomeprol 400/100 mg I/mL), 10% povidone–iodine (PV–I), 240/240 g/mL barium sulphate and a mixture of equal amounts of all contrast agents. A radiation dose detector was placed in coated latex gloves for each one. The absorption values of radiation from latex gloves coated with various contrast agents were measured and compared with the absorption of radiation from lead gloves. This study was designed as an ‘experimental study’. Results: The mean absorption value of X-ray from lead gloves was 3.0±0.08 µG/s. The mean absorption values of X-ray from latex gloves coated with various contrast agents were 3.7±0.09 µG/s (iopromide 370/100 mg I/mL), 3.6±0.09 µG/s (iomeprol 400/100 mg I/mL), 3.7±0.04 µG/s (PV–I), 3.1±0.07 µG/s (barium sulphate) and 3.8±0.05 µG/s (mixture of all contrast agents). Latex gloves coated with barium sulphate provided the best radiation absorption compared with latex gloves coated with other radiodense contrast agents. Conclusion: Latex gloves coated with barium sulphate may provide protection equivalent to lead gloves. PMID:26680548

Biological Weapons and Modern Warfare

DTIC Science & Technology

1991-04-01

every preparation for reducing Its effectiveness and thereby reduce the likelihood of Its use. In order to plan such preparation, It is advantageous to...attack rates could be maximized and the forces using the weapon protected from its effects . In today’s climate, BW agents are also attractive weapons...questions about the agreement’s true effectiveness . Verification of compliance was not addressed. D. World War It: Events during and following World War

Antidiabetic drugs of plant origin used in China: compositions, pharmacology, and hypoglycemic mechanisms.

PubMed

Jia, Wei; Gao, Wen-yuan; Xiao, Pei-gen

2003-02-01

The paper reviewed compositions and pharmacological effects of eight antidiabetic herbal drugs that have been approved by health regulatory agency for commercial use in China. Investigators attributed the hypoglycemic effect of these products to their ability to restore the functions of pancreatic tissues and cause an increase in insulin output, to inhibit the intestinal absorption of glucose, or to the facilitation of metabolites in insulin-dependent processes. Treatment with herbal drugs has an effect on protecting beta cells and smoothing out fluctuations in glucose levels. The use of these naturally derived agents in conjunction with conventional drug treatments such as an chemical agent or insulin permits the use of lower doses of the drug and/or decreased frequency of administration which decreases the side effects most commonly observed.

Is the efficacy of biological control against plant diseases likely to be more durable than that of chemical pesticides?

PubMed Central

Bardin, Marc; Ajouz, Sakhr; Comby, Morgane; Lopez-Ferber, Miguel; Graillot, Benoît; Siegwart, Myriam; Nicot, Philippe C.

2015-01-01

The durability of a control method for plant protection is defined as the persistence of its efficacy in space and time. It depends on (i) the selection pressure exerted by it on populations of plant pathogens and (ii) on the capacity of these pathogens to adapt to the control method. Erosion of effectiveness of conventional plant protection methods has been widely studied in the past. For example, apparition of resistance to chemical pesticides in plant pathogens or pests has been extensively documented. The durability of biological control has often been assumed to be higher than that of chemical control. Results concerning pest management in agricultural systems have shown that this assumption may not always be justified. Resistance of various pests to one or several toxins of Bacillus thuringiensis and apparition of resistance of the codling moth Cydia pomonella to the C. pomonella granulovirus have, for example, been described. In contrast with the situation for pests, the durability of biological control of plant diseases has hardly been studied and no scientific reports proving the loss of efficiency of biological control agents against plant pathogens in practice has been published so far. Knowledge concerning the possible erosion of effectiveness of biological control is essential to ensure a durable efficacy of biological control agents on target plant pathogens. This knowledge will result in identifying risk factors that can foster the selection of strains of plant pathogens resistant to biological control agents. It will also result in identifying types of biological control agents with lower risk of efficacy loss, i.e., modes of action of biological control agents that does not favor the selection of resistant isolates in natural populations of plant pathogens. An analysis of the scientific literature was then conducted to assess the potential for plant pathogens to become resistant to biological control agents. PMID:26284088

Caffeic Acid Phenethyl Ester: A Review of Its Antioxidant Activity, Protective Effects against Ischemia-reperfusion Injury and Drug Adverse Reactions.

PubMed

Tolba, Mai F; Omar, Hany A; Azab, Samar S; Khalifa, Amani E; Abdel-Naim, Ashraf B; Abdel-Rahman, Sherif Z

2016-10-02

Propolis, a honey bee product, has been used in folk medicine for centuries for the treatment of abscesses, canker sores and for wound healing. Caffeic acid phenethyl ester (CAPE) is one of the most extensively investigated active components of propolis which possess many biological activities, including antibacterial, antiviral, antioxidant, anti-inflammatory, and anti-cancer effects. CAPE is a polyphenolic compound characterized by potent antioxidant and cytoprotective activities and protective effects against ischemia-reperfusion (I/R)-induced injury in multiple tissues such as brain, retina, heart, skeletal muscles, testis, ovaries, intestine, colon, and liver. Furthermore, several studies indicated the protective effects of CAPE against chemotherapy-induced adverse drug reactions (ADRs) including several antibiotics (streptomycin, vancomycin, isoniazid, ethambutol) and chemotherapeutic agents (mitomycin, doxorubicin, cisplatin, methotrexate). Due to the broad spectrum of pharmacological activities of CAPE, this review makes a special focus on the recently published data about CAPE antioxidant activity as well as its protective effects against I/R-induced injury and many adverse drug reactions.

Intelligent judgements over health risks in a spatial agent-based model.

PubMed

Abdulkareem, Shaheen A; Augustijn, Ellen-Wien; Mustafa, Yaseen T; Filatova, Tatiana

2018-03-20

Millions of people worldwide are exposed to deadly infectious diseases on a regular basis. Breaking news of the Zika outbreak for instance, made it to the main media titles internationally. Perceiving disease risks motivate people to adapt their behavior toward a safer and more protective lifestyle. Computational science is instrumental in exploring patterns of disease spread emerging from many individual decisions and interactions among agents and their environment by means of agent-based models. Yet, current disease models rarely consider simulating dynamics in risk perception and its impact on the adaptive protective behavior. Social sciences offer insights into individual risk perception and corresponding protective actions, while machine learning provides algorithms and methods to capture these learning processes. This article presents an innovative approach to extend agent-based disease models by capturing behavioral aspects of decision-making in a risky context using machine learning techniques. We illustrate it with a case of cholera in Kumasi, Ghana, accounting for spatial and social risk factors that affect intelligent behavior and corresponding disease incidents. The results of computational experiments comparing intelligent with zero-intelligent representations of agents in a spatial disease agent-based model are discussed. We present a spatial disease agent-based model (ABM) with agents' behavior grounded in Protection Motivation Theory. Spatial and temporal patterns of disease diffusion among zero-intelligent agents are compared to those produced by a population of intelligent agents. Two Bayesian Networks (BNs) designed and coded using R and are further integrated with the NetLogo-based Cholera ABM. The first is a one-tier BN1 (only risk perception), the second is a two-tier BN2 (risk and coping behavior). We run three experiments (zero-intelligent agents, BN1 intelligence and BN2 intelligence) and report the results per experiment in terms of several macro metrics of interest: an epidemic curve, a risk perception curve, and a distribution of different types of coping strategies over time. Our results emphasize the importance of integrating behavioral aspects of decision making under risk into spatial disease ABMs using machine learning algorithms. This is especially relevant when studying cumulative impacts of behavioral changes and possible intervention strategies.

Role of mono- and oligosaccharides from FOS as stabilizing agents during freeze-drying and storage of Lactobacillus delbrueckii subsp. bulgaricus.

PubMed

Romano, Nelson; Schebor, Carolina; Mobili, Pablo; Gómez-Zavaglia, Andrea

2016-12-01

The aim of this work was to assess the role of mono- and oligosaccharides present in fructo-oligosaccharides (FOS) mixtures as protective agents during freeze-drying and storage of Lactobacillus delbrueckii subsp. bulgaricus CIDCA 333. Different FOS mixtures were enzymatically obtained from sucrose and further purified by removing the monosaccharides produced as secondary products. Their glass transition temperatures (T g ) were determined at 11, 22 and 33% relative humidity (RH). Bacterial cultures were freeze-dried in the presence of 20% w/v solutions of the studied FOS. Their protective effect during freeze-drying was assessed by bacterial plate counting, and by determining the lag time from growth kinetics and the uptake of propidium iodide (PI). Plate counting during bacterial storage at 4°C, and 11, 22 and 33% RH for 80days completed this rational analysis of the protective effect of FOS. Purification of FOS led to an increase of T g in all the conditions assayed. Microorganisms freeze-dried in the presence of non-purified FOS were those with the shortest lag times. Bacteria freeze-dried with pure or commercial FOS (92% of total FOS) showed larger lag times (8.9-12.6h). The cultivability of microorganisms freeze-dried with non-purified FOS and with sucrose was not significantly different from that of bacteria before freeze-drying (8.74±0.14logCFU/mL). Pure or commercial FOS were less efficient in protecting bacteria during freeze-drying. All the protectants prevented membrane damage. The cultivability of bacteria freeze-dried with FOS decayed <1logarithmicunit after 80days of storage at 11% RH. When storing at 22 and 33% RH, pure and commercial FOS were those that best protected bacteria, and FOS containing monosaccharides were less efficient. The effect of FOS on bacterial protection is the result of a balance between monosaccharides, sucrose and larger FOS in the mixtures: the smallest sugars are more efficient in protecting lipid membranes, and the larger ones favor the formation of vitreous states. Copyright © 2016 Elsevier Ltd. All rights reserved.

78 FR 41930 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-12

... sources, undetermined transmission, or undetermined risk factors. These EEIs represent a subset of those... transmission, or risk factors to effectively implement rapid prevention and control measures to protect the...; data are analyzed to determine the agents, sources, modes of transmission, or risk factors so that...

In silico and in vivo characterization of cabralealactone, solasodin and salvadorin in a rat model: potential anti-inflammatory agents

PubMed Central

Malik, Arif; Arooj, Mahwish; Butt, Tariq Tahir; Zahid, Sara; Zahid, Fatima; Jafar, Tassadaq Hussain; Waquar, Sulayman; Gan, Siew Hua; Ahmad, Sarfraz; Mirza, Muhammad Usman

2018-01-01

Background The present study investigates the hepato- and DNA-protective effects of standardized extracts of Cleome brachycarpa (cabralealactone), Solanum incanum (solasodin), and Salvadora oleioides (salvadorin) in rats. Materials and methods Hepatotoxicity was induced with intraperitoneal injection of carbon tetrachloride (CCl4) (1 mL/kg b.wt.) once a week for 12 weeks. The hepato- and DNA protective effects of the extracts in different combinations were compared with that of a standard drug Clavazin (200 mg/kg b.wt.). Tissue alanine aminotransferase, alpha-fetoprotein, tumor necrosis factor alpha (TNF-α), isoprostanes-2α, malondialdehyde, and 8-hydroxydeoxyguanosine, the significant hallmarks of oxidative stress, were studied. Results Histopathological findings of the liver sections from the rat group which received CCl4+cabralealactone, solasodin, and salvadorin demonstrated improved centrilobular hepatocyte regeneration with moderate areas of congestion and infiltration comparable with Clavazin. For in silico study, the identified compounds were subjected to molecular docking with cyclooxygenase-2 and TNF-α followed by a molecular dynamics study, which indicated their potential as anti-inflammatory agents. Conclusion Cabralealactone, solasodin, and salvadorin confer some hepatoprotective and DNA-damage protective effects against CCl4-induced toxicity. They successfully restored the normal architecture of hepatocytes and have the potential to be used as inhibitor to main culprits, that is, cyclooxygenase-2 and TNF-α. They can combat oxidative stress and liver injuries both as mono and combinational therapies. However, combination therapy has more ameliorating effects. PMID:29872266

Anti-inflammatory and neuroprotective effects of sanguinarine following cerebral ischemia in rats.

PubMed

Wang, Qin; Dai, Peng; Bao, Han; Liang, Ping; Wang, Wei; Xing, An; Sun, Jianbin

2017-01-01

Stroke is one of the leading causes of mortality worldwide. Protective agents that can diminish injuries caused by cerebral ischemia-reperfusion (I/R) are important in alleviating the harmful outcomes of stroke. The aim of the present study was to investigate the protective role of sanguinarine in cerebral I/R injury. A rat middle cerebral artery occlusion model was used to assess the clinical effect of sanguinarine, and inflammatory cytokines in the serum were detected by ELISA. Western blotting was performed to examine the change in levels of apoptosis-associated proteins in the injured brains. The results suggested that sanguinarine, an anti-inflammatory agent derived from the roots of Sanguinaria canadensis , improved the state of cerebral ischemia in a rat model. The data demonstrated that when rats were treated with sanguinarine prior to middle cerebral artery occlusion, the infarct volume was reduced significantly. The inflammatory factors tumor necrosis factor-α, interleukin (IL)-6 and IL-1β were measured in sanguinarine and vehicle-treated groups using an enzyme-linked immunosorbent assay, and the expression levels of the three factors were significantly reduced following treatment with sanguinarine (P<0.05). In addition, western blot analysis demonstrated that the ratio of B-cell lymphoma 2/Bcl-2-associated X protein was significantly increased following treatment with sanguinarine (P<0.05). The study demonstrated that sanguinarine exerts a protective effect in cerebral ischemia, and that this effect is associated with the anti-inflammatory and anti-apoptotic properties of sanguinarine.

Cysteamine-colon and cysteamine-duodenum lesions in rats. Attenuation by gastric pentadecapeptide BPC 157, cimetidine, ranitidine, atropine, omeprazole, sulphasalazine and methylprednisolone.

PubMed

Sikiric, P; Seiwerth, S; Grabarevic, Z; Balen, I; Aralica, G; Gjurasin, M; Komericki, L; Perovic, D; Ziger, T; Anic, T; Prkacin, I; Separovic, J; Stancic-Rokotov, D; Lovric-Bencic, M; Mikus, D; Staresinic, M; Aralica, J; DiBiaggio, N; Simec, Z; Turkovic, B; Rotkvic, I; Mise, S; Rucman, R; Petek, M; Sebecic, B; Ivasovic, Z; Boban-Blagaic, A; Sjekavica, I

2001-01-01

Recently, we showed cysteamine-duodenal lesions without gastric acid, since they were induced also in gastrectomized rats, as in naive rats, and they were inhibited by the novel stomach pentadecapeptide BPC 157 as well as standard antiulcer drugs (i.e. cimetidine, ranitidine, omeprazole, bromocriptine, atropine). Therefore, as an advantage of considering cysteamine as a directly acting cytotoxic agent and mentioned agents as direct cytoprotective agents, the present focus was on the ulcerogenic effect of cysteamine and protective effect of gastroduodenal antiulcer agents outside upper gastrointestinal tract (i.e. in colon). Intrarectal administration of the cysteamine (200 or 400 mg/kg b.w) produced severe colon lesions (i.e. transmural inflammation with serosal involvement) in rats (30 min-72 h-experimental period), apparently distinctive from smaller lesions after non-specific irritant enema [diluted HCl solution, pH 3.8 (adjusted to pH of cysteamine solution (pH 3.8)]. All of the tested antiulcer agents were applied simultaneously with cysteamine enema (8 cm from the anus, in a volume of the 1.0 ml/rat) intraperitoneally (i.p.), intragastrically (i.g.) or intrarectally (i.r.). Pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w.), given in either regimen, previously shown to have, besides others, a particular beneficial activity just in the intestinal mucosa, inhibited these cysteamine colon lesions (assessed after 30 min, 60 min, 180 min, 24 h, 48 h, 72 h following cysteamine in a dose of either 200 or 400 mg/kg i.r.). Cysteamine-colon lesions were also attenuated by standard antiulcer agents (mg/kg b.w.), given i.p., i.g., or i.r., such as ranitidine (10), cimetidine (50), omeprazole (10), atropine (10), together with methylprednisolone (1), and sulphasalazine (50, i.r.), assessed 30 min following application of 200 mg of cysteamine. Finally, standard cysteamine duodenal lesions (assessed 24 h after a subcutaneous application of 400 mg/kg of cysteamine) were also attenuated by these agents application (given in the same doses, i.p., 1 h before cysteamine), with only exception to sulphasalazine. Thus, the extended cysteamine specific ulcerogenic effect, cysteamine colon/duodenum lesion-link and an extenuation of agents protection from upper to lower part of gastrointestinal tract (i.e. stomach pentadecapeptide BPC 157, standard antiulcer agents, cimetidine, ranitidine, atropine, omeprazole) and vice versa (remedies for inflammatory bowel disease) evidenced in the present study may be potentially important for both further experimental and clinical research.

Prophylactic effects of humic acid-glucan combination against experimental liver injury

PubMed Central

Vetvicka, Vaclav; Garcia-Mina, Jose Maria; Yvin, Jean-Claude

2015-01-01

Aim: Despite intensive research, liver diseases represent a significant health problem and current medicine does not offer a substance able to significantly inhibit the hepatotoxicity leading to various stages of liver disease. Based on our previously published studies showing the protective effects of a glucan-humic acid (HA) combination, we focused on the hypothesis that the combination of these two natural molecules can offer prophylactic protection against experimentally induced hepatotoxicity. Materials and Methods: Lipopolysaccharide, carbon tetrachloride, and ethanol were used to experimentally damage the liver. Levels of aspartate aminotransferase, alanine transaminase, alkaline phosphatase, glutathione, superoxide dismutase, and malondialdehyde, known to correspond to the liver damage, were assayed. Results: Using three different hepatotoxins, we found that in all cases, some samples of HA and most of all the glucan-HA combination, offer strong protection against liver damage. Conclusion: Glucan-HA combination is a promising agent for use in liver protection. PMID:26401416

In vitro protective effects of botryosphaeran, a (1→3;1→6)-β-d-glucan, against mutagens in normal and tumor rodent cells.

PubMed

Kerche-Silva, Leandra E; Cólus, Ilce M S; Malini, Maressa; Mori, Mateus Prates; Dekker, Robert F H; Barbosa-Dekker, Aneli M

2017-02-01

Botryosphaeran (BOT) is an exocellular β-d-glucan (carbohydrate biopolymer) of the (1→3;1→6)-linked type produced by Botryosphaeria rhodina MAMB-05. The cytotoxic, mutagenic, genotoxic, and protective effects of this substance were evaluated in Chinese hamster lung fibroblasts (V79) and rat hepatocarcinoma cells (HTC) by the micronucleus test (MN) and the comet assay. BOT was not genotoxic in either cell line; it decreased the clastogenic effects of doxorubicin, H 2 O 2 , and benzo[a]pyrene. These results indicate that BOT may have potential as a therapeutic agent. Copyright © 2016 Elsevier B.V. All rights reserved.

Sodium metabisulphite, a preservative agent, decreases the heart capillary volume and length, and curcumin, the main component of Curcuma longa, cannot protect it.

PubMed

Noorafshan, A; Asadi-Golshan, R; Monjezi, S; Karbalay-Doust, S

2014-01-01

Sodium metabisulphite is used as an antioxidant agent in many pharmaceutical formulations. It is extensively used as a food preservative and disinfectant. It has been demonstrated that sulphite exposure can affect some organs. Curcumin, the main element of Curcuma longa, has been identified to have multiple protective properties. The present study extends the earlier works to quantitative evaluation of the effects of sulphite and curcumin on the heart structure using stereological methods. In this study, 28 rats were randomly divided into four experimental groups. The rats in groups I to IV received distilled water (group I), sodium metabisulphite (25 mg/ kg/day) (group II), curcumin (100 mg/kg/day) (group III), and sodium metabisulphite+curcumin (group IV), respectively, for 8 weeks. The left ventricle was subjected to stereological methods to estimate the quantitative parameters of the myocardium. A 20 % decrease was observed in the total volume of ventricular tissue in the sulphite-treated animals compared to the distilled water treatment (P < 0.02). Also, the volume and length of the capillaries were reduced by 43 % on average in the sulphite-treated rats in comparison to the distilled water-treated animals (P < 0.02). However, no significant change was seen in the mean and total volume of the myocardium and the cavity and diameter of the capillaries after sulphite ingestion. Treatment with curcumin did not protect the animals against the structural changes of the ventricle. Sulphite, as a preservative food agent, reduced the length and volume of the ventricular capillaries and curcumin could not protect them.

Expression in mammalian cells of the Escherichia coli O6 alkylguanine-DNA-alkyltransferase gene ogt reduces the toxicity of alkylnitrosoureas.

PubMed Central

Harris, L. C.; Margison, G. P.

1993-01-01

V79 Chinese hamster cells expressing either the O6-alkylguanine-DNA-alkyltransferase (ATase) encoded by the E. coli ogt gene or a truncated version of the E. coli ada gene have been exposed to various alkylnitrosoureas to investigate the contribution of ATase repairable lesions to the toxicity of these compounds. Both ATases are able to repair O6-alkylguanine (O6-AlkG) and O4-alkylthymine (O4-AlkT) but the ogt ATase is more efficient in the repair of O4-methylthymine (O4-MeT) and higher alkyl derivatives of O6-AlkG than is the ada ATase. Expression of the ogt ATase provided greater protection against the toxic effects of the alkylating agents then the ada ATase particularly with N-ethyl-N-nitrosourea (ENU) and N-butyl-N-nitrosourea (BNU) to which the ada ATase expressing cells were as sensitive as parent vector transfected cells. Although ogt was expressed at slightly higher levels than the truncated ada in the transfected cells, this could not account for the differential protection observed. For-N-methyl-N-nitrosourea (MNU) the increased protection in ogt-transfected cells is consistent with O4-MeT acting as a toxic lesion. For the longer chain alkylating agents and chloroethylating agents, the protection afforded by the ogt protein may be a consequence of the more efficient repair of O6-AlkG, O4-AlkT or both of these lesions in comparison with the ada-encoded ATase. Images Figure 2 Figure 3 PMID:8512805

Infectious Agents in Childhood Leukemia.

PubMed

Arellano-Galindo, José; Barrera, Alberto Parra; Jiménez-Hernández, Elva; Zavala-Vega, Sergio; Campos-Valdéz, Guillermina; Xicohtencatl-Cortes, Juan; Ochoa, Sara A; Cruz-Córdova, Ariadnna; Crisóstomo-Vázquez, María Del Pilar; Fernández-Macías, Juan Carlos; Mejía-Aranguré, Juan Manuel

2017-05-01

Acute leukemia is the most common pediatric cancer, representing one-third of all cancers that occurs in under 15 year olds, with a varied incidence worldwide. Although a number of advances have increased the knowledge of leukemia pathophysiology, its etiology remains less well understood. The role of infectious agents, such as viruses, bacteria, or parasites, in the pathogenesis of leukemia has been discussed. To date, several cellular mechanisms involving infectious agents have been proposed to cause leukemia following infections. However, although leukemia can be triggered by contact with such agents, they can also be beneficial in developing immune stimulation and protection despite the risk of leukemic clones. In this review, we analyze the proposed hypotheses concerning how infectious agents may play a role in the origin and development of leukemia, as well as in a possible mechanism of protection following infections. We review reported clinical observations associated with vaccination or breastfeeding, that support hypotheses such as early life exposure and the resulting early immune stimulation that lead to protection. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

Human Hair as a Natural Sun Protection Agent: A Quantitative Study.

PubMed

de Gálvez, María Victoria; Aguilera, José; Bernabó, Jean-Luc; Sánchez-Roldán, Cristina; Herrera-Ceballos, Enrique

2015-01-01

The rising incidence of skin cancers attributable to excessive sun exposure has become a major health concern worldwide. While numerous studies have analyzed the sun protective effect of sunscreens, clothing and antioxidants, none to date have measured the photoprotective effect of hair, despite clinical evidence that individuals with balding or thinning hair are at greater risk of skin lesions that can progress to cancer, hence the recommendation to use hats or umbrellas. We analyzed the level of protection offered by hair according to hair density, thickness and color using the spectral transmittance and corrected for relative erythema effectiveness. Our results show that hair provides a barrier against both UVB and UVA radiation which is significantly increased with respect to the hair density, thickness and the presence of melanins. This is the first study to quantify sun protection factor offered by hair, namely hair ultraviolet protection factor (HUPF). We believe that hair should be recognized as an important natural sun barrier in the prevention of UV-induced skin cancers. © 2015 The American Society of Photobiology.

Antiviral activity of ovine interferon tau 4 against foot-and-mouth disease virus.

PubMed

Usharani, Jayaramaiah; Park, Sun Young; Cho, Eun-Ju; Kim, Chungsu; Ko, Young-Joon; Tark, Dongseob; Kim, Su-Mi; Park, Jong-Hyeon; Lee, Kwang-Nyeong; Lee, Myoung-Heon; Lee, Hyang-Sim

2017-07-01

Foot-and-mouth disease (FMD) is an economically important disease in most parts of the world and new therapeutic agents are needed to protect the animals before vaccination can trigger the host immune response. Although several interferons have been used for their antiviral activities against Foot-and-mouth disease virus (FMDV), ovine interferon tau 4 (OvIFN-τ4), with a broad-spectrum of action, cross-species antiviral activity, and lower incidence of toxicity in comparison to other type І interferons, has not yet been evaluated for this indication. This is the first study to evaluate the antiviral activity of OvIFN-τ4 against various strains of FMDV. The effective anti-cytopathic concentration of OvIFN-τ4 and its effectiveness pre- and post-infection with FMDV were tested in vitro in LFBK cells. In vivo activity of OvIFN-τ4 was then confirmed in a mouse model of infection. OvIFN-τ4 at a concentration of 500 ng, protected mice until 5days post-FMDV challenge and provided 90% protection for 10 days following FMDV challenge. These results suggest that OvIFN-τ4 could be used as an alternative to other interferons or antiviral agents at the time of FMD outbreak. Copyright © 2017. Published by Elsevier B.V.

Survival of viral biowarfare agents in disinfected waters.

PubMed

Wade, Mary Margaret; Chambers, Amanda E; Insalaco, Joseph M; Zulich, Alan W

2010-01-01

Protecting civilian and military water supplies has received more attention since the United States began its war on terror in 2001. Both chlorine and bromine are used by branches of the U.S. military for disinfecting water supplies; however, limited data exists as to the effectiveness of these additives when used against viral biowarfare agents. The present study sought to evaluate the survival of selected viral biothreat agents in disinfected water. Disinfected water samples were spiked with vaccinia virus strain WR and Venezuelan equine encephalitis (VEE) virus strain TC-83 each separately to a final concentration of approximately 1 × 10(6) PFU/mL, and survival was assessed by plaque assay. Both viruses were inactivated by 1 mg/L free available chlorine (FAC) and 2mg/L total bromine within one hour. In conclusion, these results demonstrate that both chlorine and bromine are effective disinfectants against vaccinia virus and VEE strain TC-83 at the concentrations tested.

Increasing nerve agent treatment efficacy by P-glycoprotein inhibition.

PubMed

Joosen, Marloes J A; Vester, Stefanie M; Hamelink, Jouk; Klaassen, Steven D; van den Berg, Roland M

2016-11-25

One of the shortcomings of current treatment of nerve agent poisoning is that not all drugs effectively penetrate the blood-brain barrier (BBB), whereas most nerve agents easily do. P-glycoprotein (Pgp) efflux transporters at the BBB may contribute to this aspect. It was previously shown that Pgp inhibition by tariquidar enhanced the efficacy of nerve agent treatment when administered as a pretreatment. In the present study soman-induced seizures were also substantially prevented when the animals were intravenously treated with tariquidar post-poisoning, in addition to HI-6 and atropine. In these animals, approximately twice as much AChE activity was present in their brain as compared to control rats. The finding that tariquidar did not affect distribution of soman to the brain indicates that the potentiating effects were a result of interactions of Pgp inhibition with drug distribution. In line with this, atropine appeared to be a substrate for Pgp in in vitro studies in a MDR1/MDCK cell model. This indicates that tariquidar might induce brain region specific effects on atropine distribution, which could contribute to the therapeutic efficacy increase found. Furthermore, the therapeutic enhancement by tariquidar was compared to that of the less specific and less potent Pgp inhibitor cyclosporine A. This compound appeared to induce a protective effect similar to tariquidar. In conclusion, treatment with a Pgp inhibitor resulted in enhanced therapeutic efficacy of HI-6 and atropine in a soman-induced seizure model in the rat. The mechanism underlying these effects should be further investigated. To that end, the potentiating effect of nerve agent treatment should be addressed against a broader range of nerve agents, for oximes and atropine separately, and for those at lower doses. In particular when efficacy against more nerve agents is shown, a Pgp inhibitor such as tariquidar might be a valid addition to nerve agent antidotes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

1,5 iodonaphthyl Azide Inactivated V3526 Protects against Aerosol Challenge with Virulent Venezuelan Equine Encephalitis Virus.

DTIC Science & Technology

2016-06-02

against VEEV. VEEV is highly infectious in aerosolized form and has been identified as a bio -terrorism agent. The current IND vaccine is poorly...protective response as well as residual virulence associated with the live attenuated vaccine candidates [1]. VEEV is also a bio -threat agent, thereby; any

Statin-Induced Cardioprotection Against Ischemia-Reperfusion Injury: Potential Drug-Drug Interactions. Lesson to be Learnt by Translating Results from Animal Models to the Clinical Settings.

PubMed

Birnbaum, Gilad D; Birnbaum, Itamar; Ye, Yumei; Birnbaum, Yochai

2015-01-01

Numerous interventions have been shown to limit myocardial infarct size in animal models; however, most of these interventions have failed to have a significant effect in clinical trials. One potential explanation for the lack of efficacy in the clinical setting is that in bench models, a single intervention is studied without the background of other interventions or modalities. This is in contrast to the clinical setting in which new medications are added to the "standard of care" treatment that by now includes a growing number of medications. Drug-drug interaction may lead to alteration, dampening, augmenting or masking the effects of the intended intervention. We use the well described model of statin-induced myocardial protection to demonstrate potential interactions with agents which are commonly concomitantly used in patients with stable coronary artery disease and/or acute coronary syndromes. These interactions could potentially explain the reduced efficacy of statins in the clinical trials compared to the animal models. In particular, caffeine and aspirin could attenuate the infarct size limiting effects of statins; morphine could delay the onset of protection or mask the protective effect in patients with ST elevation myocardial infarction, whereas other anti-platelet agents (dipyridamole, cilostazol and ticagrelor) may augment (or mask) the effect due to their favorable effects on adenosine cell reuptake and intracellular cAMP levels. We recommend that after characterizing the effects of new modalities in single intervention bench research, studies should be repeated in the background of standard-of-care medications to assure that the magnitude of the effect is not altered before proceeding with clinical trials.

Percutaneous toxicity and decontamination of soman, VX, and paraoxon in rats using detergents.

PubMed

Misík, Jan; Pavliková, Růžena; Kuča, Kamil

2013-06-01

Highly toxic organophosphorus compounds (OPs) were originally developed for warfare or as agricultural pesticides. Today, OPs represent a serious threat to military personnel and civilians. This study investigates the in vivo decontamination of male Wistar rats percutaneously exposed to paraoxon and two potent nerve agents--soman (GD) and VX. Four commercial detergents were tested as decontaminants--Neodekont(TM), Argos(TM), Dermogel(TM), and FloraFree(TM). Decontamination performed 2 min after exposure resulted in a higher survival rate in comparison with non-decontaminated controls. The decontamination effectiveness was expressed as protective ratio (PR, median lethal dose of agent in decontaminated animals divided by the median lethal dose of agent in untreated animals). The highest decontamination effectiveness was consistently achieved with Argos(TM) (PR=2.3 to 64.8), followed by Dermogel(TM) (PR=2.4 to 46.1). Neodekont(TM) and FloraFree(TM) provided the lowest decontamination effectiveness, equivalent to distilled water (PR=1.0 to 43.2).

Effect of controlled ice nucleation on primary drying stage and protein recovery in vials cooled in a modified freeze-dryer.

PubMed

Passot, Stéphanie; Tréléa, Ioan Cristian; Marin, Michèle; Galan, Miquel; Morris, G John; Fonseca, Fernanda

2009-07-01

The freezing step influences lyophilization efficiency and protein stability. The main objective of this work was to investigate the impact on the primary drying stage of an ultrasound controlled ice nucleation technology, compared with usual freezing protocols. Lyophilization cycles involving different freezing protocols (applying a constant shelf cooling rate of 1 degrees C/min or 0.2 degrees C/min, putting vials on a precooled shelf, and controlling nucleation by ultrasounds or by addition of a nucleating agent) were performed in a prototype freeze-dryer. Three protective media including sucrose or maltodextrin and differing by their thermal properties and their ability to preserve a model protein (catalase) were used. The visual aspect of the lyophilized cake, residual water content, and enzymatic activity recovery of catalase were assessed after each lyophilization cycle and after 1 month of storage of the lyophilized product at 4 degrees C and 25 degrees C. The freezing protocols allowing increasing nucleation temperature (precooled shelf and controlled nucleation by using ultrasounds or a nucleating agent) induced a faster sublimation step and higher sublimation rate homogeneity. Whatever the composition of the protective medium, applying the ultrasound technology made it possible to decrease the sublimation time by 14%, compared with the freezing method involving a constant shelf cooling rate of 1 degrees C/min. Concerning the enzyme activity recovery, the impact of the freezing protocol was observed only for the protective medium involving maltodextrin, a less effective protective agent than sucrose. Higher activity recovery results were obtained after storage when the ultrasound technology or the precooled shelf method was applied. Controlling ice nucleation during the freezing step of the lyophilization process improved the homogeneity of the sublimation rates, which will, in turn, reduce the intervial heterogeneity. The freeze-dryer prototype including the system of controlled nucleation by ultrasounds appears to be a promising tool in accelerating sublimation and improving intrabatch homogeneity.

Administration of the antitumor drug mitoguazone protects normal thymocytes against spontaneous and etoposide-induced apoptosis.

PubMed

Ferioli, M E; Bottone, M G; Soldani, C; Pellicciari, C

2004-11-01

The suggestion has been made that polyamines may be involved in the control of cell death, since exceedingly high or low levels induce apoptosis in different cell systems. For a deeper insight into the relationship between apoptosis and polyamine metabolism, we investigated in vitro the effect on rat thymocytes of mitoguazone (MGBG, which inhibits S-adenosylmethionine decarboxylase, i.e. a key enzyme in the polyamine biosynthetic pathway). Thymocytes were selected as an especially suitable model system, since they undergo spontaneous apoptosis in vivo and can be easily induced to apoptose in vitro by etoposide, used here as an apoptogenic agent. MGBG protected thymocytes from both spontaneous and drug-induced apoptosis, and this protective effect was associated with a decrease in polyamine oxidase activity and total polyamine levels.

Reevaluation of 1999 Health-Based Environmental Screening Levels (HBESLs) for Chemical Warfare Agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watson, Annetta Paule; Dolislager, Fredrick G

2007-05-01

This report evaluates whether new information and updated scientific models require that changes be made to previously published health-based environmental soil screening levels (HBESLs) and associated environmental fate/breakdown information for chemical warfare agents (USACHPPM 1999). Specifically, the present evaluation describes and compares changes that have been made since 1999 to U.S. Environmental Protection Agency (EPA) risk assessment models, EPA exposure assumptions, as well as to specific chemical warfare agent parameters (e.g., toxicity values). Comparison was made between screening value estimates recalculated with current assumptions and earlier health-based environmental screening levels presented in 1999. The chemical warfare agents evaluated include themore » G-series and VX nerve agents and the vesicants sulfur mustard (agent HD) and Lewisite (agent L). In addition, key degradation products of these agents were also evaluated. Study findings indicate that the combined effect of updates and/or changes to EPA risk models, EPA default exposure parameters, and certain chemical warfare agent toxicity criteria does not result in significant alteration to the USACHPPM (1999) health-based environmental screening level estimates for the G-series and VX nerve agents or the vesicant agents HD and L. Given that EPA's final position on separate Tier 1 screening levels for indoor and outdoor worker screening assessments has not yet been released as of May 2007, the study authors find that the 1999 screening level estimates (see Table ES.1) are still appropriate and protective for screening residential as well as nonresidential sites. As such, risk management decisions made on the basis of USACHPPM (1999) recommendations do not require reconsideration. While the 1999 HBESL values are appropriate for continued use as general screening criteria, the updated '2007' estimates (presented below) that follow the new EPA protocols currently under development are also protective. When EPA finalizes and documents a position on the matter of indoor and outdoor worker screening assessments, site-specific risk assessments should make use of modified models and criteria. Screening values such as those presented in this report may be used to assess soil or other porous media to determine whether chemical warfare agent contamination is present as part of initial site investigations (whether due to intentional or accidental releases) and to determine whether weather/decontamination has adequately mitigated the presence of agent residual to below levels of concern. However, despite the availability of scientifically supported health-based criteria, there are significant resources needs that should be considered during sample planning. In particular, few analytical laboratories are likely to be able to meet these screening levels. Analyses will take time and usually have limited confidence at these concentrations. Therefore, and particularly for the more volatile agents, soil/destructive samples of porous media should be limited and instead enhanced with headspace monitoring and presence-absence wipe sampling.« less

Human Carboxylesterase 1 Stereoselectively Binds the Nerve Agent Cyclosarin and Spontaneously Hydrolyzes the Nerve Agent Sarin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hemmert, Andrew C.; Otto, Tamara C.; Wierdl, Monika

Organophosphorus (OP) nerve agents are potent toxins that inhibit cholinesterases and produce a rapid and lethal cholinergic crisis. Development of protein-based therapeutics is being pursued with the goal of preventing nerve agent toxicity and protecting against the long-term side effects of these agents. The drug-metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based therapeutic because of its similarity in structure and function to the cholinesterase targets of nerve agent poisoning. However, the ability of wild-type hCE1 to process the G-type nerve agents sarin and cyclosarin has not been determined. We report the crystal structure of hCE1 in complex withmore » the nerve agent cyclosarin. We further use stereoselective nerve agent analogs to establish that hCE1 exhibits a 1700- and 2900-fold preference for the P{sub R} enantiomers of analogs of soman and cyclosarin, respectively, and a 5-fold preference for the P{sub S} isomer of a sarin analog. Finally, we show that for enzyme inhibited by racemic mixtures of bona fide nerve agents, hCE1 spontaneously reactivates in the presence of sarin but not soman or cyclosarin. The addition of the neutral oxime 2,3-butanedione monoxime increases the rate of reactivation of hCE1 from sarin inhibition by more than 60-fold but has no effect on reactivation with the other agents examined. Taken together, these data demonstrate that hCE1 is only reactivated after inhibition with the more toxic P{sub S} isomer of sarin. These results provide important insights toward the long-term goal of designing novel forms of hCE1 to act as protein-based therapeutics for nerve agent detoxification.« less

Toxicology of organophosphorus compounds in view of an increasing terrorist threat.

PubMed

Worek, Franz; Wille, Timo; Koller, Marianne; Thiermann, Horst

2016-09-01

The implementation of the Chemical Weapon Convention (CWC), prohibiting the development, production, storage and use of chemical weapons by 192 nations and the ban of highly toxic OP pesticides, especially class I pesticides according to the WHO classification, by many countries constitutes a great success of the international community. However, the increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents new challenges to our societies. Almost seven decades of research on organophosphorus compound (OP) toxicology was mainly focused on a small number of OP nerve agents despite the fact that a huge number of OP analogues, many of these agents having comparable toxicity to classical nerve agents, were synthesized and published. Only limited physicochemical, toxicological and medical information on nerve agent analogues is available in the open literature. This implies potential gaps of our capabilities to detect, to decontaminate and to treat patients if nerve agent analogues are disseminated and may result in inadequate effectiveness of newly developed countermeasures. In summary, our societies may face new, up to now disregarded, threats by toxic OP which calls for increased awareness and appropriate preparedness of military and civilian CBRN defense, a broader approach for new physical and medical countermeasures and an integrated system of effective detection, decontamination, physical protection and treatment.

Are Bacterial Volatile Compounds Poisonous Odors to a Fungal Pathogen Botrytis cinerea, Alarm Signals to Arabidopsis Seedlings for Eliciting Induced Resistance, or Both?

PubMed Central

Sharifi, Rouhallah; Ryu, Choong-Min

2016-01-01

Biological control (biocontrol) agents act on plants via numerous mechanisms, and can be used to protect plants from pathogens. Biocontrol agents can act directly as pathogen antagonists or competitors or indirectly to promote plant induced systemic resistance (ISR). Whether a biocontrol agent acts directly or indirectly depends on the specific strain and the pathosystem type. We reported previously that bacterial volatile organic compounds (VOCs) are determinants for eliciting plant ISR. Emerging data suggest that bacterial VOCs also can directly inhibit fungal and plant growth. The aim of the current study was to differentiate direct and indirect mechanisms of bacterial VOC effects against Botrytis cinerea infection of Arabidopsis. Volatile emissions from Bacillus subtilis GB03 successfully protected Arabidopsis seedlings against B. cinerea. First, we investigated the direct effects of bacterial VOCs on symptom development and different phenological stages of B. cinerea including spore germination, mycelial attachment to the leaf surface, mycelial growth, and sporulation in vitro and in planta. Volatile emissions inhibited hyphal growth in a dose-dependent manner in vitro, and interfered with fungal attachment on the hydrophobic leaf surface. Second, the optimized bacterial concentration that did not directly inhibit fungal growth successfully protected Arabidopsis from fungal infection, which indicates that bacterial VOC-elicited plant ISR has a more important role in biocontrol than direct inhibition of fungal growth on Arabidopsis. We performed qRT-PCR to investigate the priming of the defense-related genes PR1, PDF1.2, and ChiB at 0, 12, 24, and 36 h post-infection and 14 days after the start of plant exposure to bacterial VOCs. The results indicate that bacterial VOCs potentiate expression of PR1 and PDF1.2 but not ChiB, which stimulates SA- and JA-dependent signaling pathways in plant ISR and protects plants against pathogen colonization. This study provides new evidence for bacterial VOC-elicited plant ISR that protects Arabidopsis plants from infection by the necrotrophic fungus B. cinerea. Our work reveals that bacterial VOCs primarily act via an indirect mechanism to elicit plant ISR, and have a major role in biocontrol against fungal pathogens. PMID:26941721

New Approaches to Radiation Protection

PubMed Central

Rosen, Eliot M.; Day, Regina; Singh, Vijay K.

2015-01-01

Radioprotectors are compounds that protect against radiation injury when given prior to radiation exposure. Mitigators can protect against radiation injury when given after exposure but before symptoms appear. Radioprotectors and mitigators can potentially improve the outcomes of radiotherapy for cancer treatment by allowing higher doses of radiation and/or reduced damage to normal tissues. Such compounds can also potentially counteract the effects of accidental exposure to radiation or deliberate exposure (e.g., nuclear reactor meltdown, dirty bomb, or nuclear bomb explosion); hence they are called radiation countermeasures. Here, we will review the general principles of radiation injury and protection and describe selected examples of radioprotectors/mitigators ranging from small-molecules to proteins to cell-based treatments. We will emphasize agents that are in more advanced stages of development. PMID:25653923

Different effects of cytoprotective drugs on ethanol- and aspirin-induced gastric mucosal injury in pylorus-ligated rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takeuchi, K.; Nishiwaki, H.; Niida, H.

In anesthetized rats oral administration (2 ml) of both ethanol (50% in 150 mM HCl) and aspirin (80 mM in 150 mM HCl) produced bandlike lesions in the stomach, while more generalized lesions occurred in the pylorus-ligated stomach when the irritant was given intragastrically through the fistula prepared in the rumen and the mucosal folds were removed by stomach distension. The bandlike lesions induced in the intact stomach by both irritants were significantly and dose-dependently prevented by 16,16-dimethyl PGE2 (dmPGE2: 3 and 10 micrograms/kg, subcutaneously), cysteamine (30 and 100 mg/kg, subcutaneously) or timoprazole (10 and 30 mg/kg, per os) atmore » the doses which significantly inhibited gastric motility. In the pylorus-ligated stomach, however, neither of these agents showed any protection against the generalized lesions induced by ethanol, but such lesions caused by aspirin were significantly prevented only by dmPGE2. These agents also showed similar effects against the reduction of transmucosal PD in the pylorus-ligated stomach exposed to ethanol and aspirin. These results suggest that (1) the formation of bandlike lesions caused by ethanol and aspirin depends on the presence of mucosal folds and may be prevented by the agents that inhibit gastric motility, (2) the pathogenesis of the lesions induced by aspirin and ethanol may be different in the pylorus-ligated stomach, and (3) dmPGE2 has a unique protective ability that is not shared by usual cytoprotective agents.« less

Intranasal Delivery of Granulocyte Colony-Stimulating Factor Enhances Its Neuroprotective Effects Against Ischemic Brain Injury in Rats.

PubMed

Sun, Bao-Liang; He, Mei-Qing; Han, Xiang-Yu; Sun, Jing-Yi; Yang, Ming-Feng; Yuan, Hui; Fan, Cun-Dong; Zhang, Shuai; Mao, Lei-Lei; Li, Da-Wei; Zhang, Zong-Yong; Zheng, Cheng-Bi; Yang, Xiao-Yi; Li, Yang V; Stetler, R Anne; Chen, Jun; Zhang, Feng

2016-01-01

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with strong neuroprotective properties. However, it has limited capacity to cross the blood-brain barrier and thus potentially limiting its protective capacity. Recent studies demonstrated that intranasal drug administration is a promising way in delivering neuroprotective agents to the central nervous system. The current study therefore aimed at determining whether intranasal administration of G-CSF increases its delivery to the brain and its neuroprotective effect against ischemic brain injury. Transient focal cerebral ischemia in rat was induced with middle cerebral artery occlusion. Our resulted showed that intranasal administration is 8-12 times more effective than subcutaneous injection in delivering G-CSF to cerebrospinal fluid and brain parenchyma. Intranasal delivery enhanced the protective effects of G-CSF against ischemic injury in rats, indicated by decreased infarct volume and increased recovery of neurological function. The neuroprotective mechanisms of G-CSF involved enhanced upregulation of HO-1 and reduced calcium overload following ischemia. Intranasal G-CSF application also promoted angiogenesis and neurogenesis following brain ischemia. Taken together, G-CSF is a legitimate neuroprotective agent and intranasal administration of G-CSF is more effective in delivery and neuroprotection and could be a practical approach in clinic.

Wine Polyphenols: Potential Agents in Neuroprotection

PubMed Central

Basli, Abdelkader; Soulet, Stéphanie; Chaher, Nassima; Mérillon, Jean-Michel; Chibane, Mohamed; Monti, Jean-Pierre; Richard, Tristan

2012-01-01

There are numerous studies indicating that a moderate consumption of red wine provides certain health benefits, such as the protection against neurodegenerative diseases. This protective effect is most likely due to the presence of phenolic compounds in wine. Wine polyphenolic compounds are well known for the antioxidant properties. Oxidative stress is involved in many forms of cellular and molecular deterioration. This damage can lead to cell death and various neurodegenerative disorders, such as Parkinson's or Alzheimer's diseases. Extensive investigations have been undertaken to determine the neuroprotective effects of wine-related polyphenols. In this review we present the neuroprotective abilities of the major classes of wine-related polyphenols. PMID:22829964

Prevention of hyperthermia-induced seizures in immature rats by a hydantoin derivative of naloxone.

PubMed

Chatterjie, N; Laorden, M L; Puig, M M; Alexander, G J

1989-01-01

The non-specific opiate antagonist naloxone protects immature rats from hyperthermic seizures which occur when the animals are exposed to an environment of 40 degrees C and 55% humidity. Most of the currently used antiepileptic therapeutic agents can be said to contain either a hydantoin or a moiety stereochemically closely related to one. We have added a hydantoin group to naloxone and created a new combined chemical, naloxyl-6-alpha spirohydantoin. The new compound was ten times as effective as naloxone against hyperthermic seizures in 15-day old rat pups. Unlike naloxone, the new naloxone-hydantoin derivative retained a protective effect 24 hrs after injection.

Wine polyphenols: potential agents in neuroprotection.

PubMed

Basli, Abdelkader; Soulet, Stéphanie; Chaher, Nassima; Mérillon, Jean-Michel; Chibane, Mohamed; Monti, Jean-Pierre; Richard, Tristan

2012-01-01

There are numerous studies indicating that a moderate consumption of red wine provides certain health benefits, such as the protection against neurodegenerative diseases. This protective effect is most likely due to the presence of phenolic compounds in wine. Wine polyphenolic compounds are well known for the antioxidant properties. Oxidative stress is involved in many forms of cellular and molecular deterioration. This damage can lead to cell death and various neurodegenerative disorders, such as Parkinson's or Alzheimer's diseases. Extensive investigations have been undertaken to determine the neuroprotective effects of wine-related polyphenols. In this review we present the neuroprotective abilities of the major classes of wine-related polyphenols.

Oligonucleotide-based theranostic nanoparticles in cancer therapy

PubMed Central

Shahbazi, Reza; Ozpolat, Bulent; Ulubayram, Kezban

2016-01-01

Theranostic approaches, combining the functionality of both therapy and imaging, have shown potential in cancer nanomedicine. Oligonucleotides such as small interfering RNA and microRNA, which are powerful therapeutic agents, have been effectively employed in theranostic systems against various cancers. Nanoparticles are used to deliver oligonucleotides into tumors by passive or active targeting while protecting the oligonucleotides from nucleases in the extracellular environment. The use of quantum dots, iron oxide nanoparticles and gold nanoparticles and tagging with contrast agents, like fluorescent dyes, optical or magnetic agents and various radioisotopes, has facilitated early detection of tumors and evaluation of therapeutic efficacy. In this article, we review the advantages of theranostic applications in cancer therapy and imaging, with special attention to oligonucleotide-based therapeutics. PMID:27102380

Protective effects of grape seed and skin extract against high-fat-diet-induced lipotoxicity in rat lung.

PubMed

El Ayed, Mohamed; Kadri, Safwen; Smine, Selima; Elkahoui, Salem; Limam, Ferid; Aouani, Ezzedine

2017-09-13

Obesity is a public health problem characterized by increased fat accumulation in different tissues. Obesity is directly linked to breathing problems and medical complications with lung, including obstructive sleep apnea syndrome, obesity hypoventilation syndrome, chronic obstructive pulmonary disease, asthma….In the present work, we aimed to investigate the effect of high fat diet (HFD) on lung lipotoxicity, oxidative stress, fatty acid composition and proportions in lung and implication in asthma development. The likely protection provided by grape seed extract (GSSE) was also investigated. In order to assess HFD effect on lung and GSSE protection we used a rat model. We analyzed the lipid plasma profile, lung peroxidation and antioxidant activities (SOD, CAT and POD). We also analyzed transition metals (Ca2+, Mg2+, Zn2+ and iron) and lung free fatty acids using gas chromatography coupled to mass spectrometry (GC-MS). HFD induced lipid profile imbalance increasing cholesterol and VLDL-C. HFD also induced an oxidative stress assessed by elevated MDA level and the drop of antioxidant activities such as SOD, CAT and POD. Moreover, HFD induced mineral disturbances by decreasing magnesium level and increasing Calcium and iron levels. HFD induced also disturbances in lung fatty acid composition by increasing oleic, stearic and arachidonic acids. Interestingly, GSSE alleviated all these deleterious effects of HFD treatment. As a whole, GSSE had a significant preventive effect against HFD-induced obesity, and hence may be used as an anti-obesity agent, and a benefic agent with potential applications against damages in lung tissue.

Groundwater protection: what can we learn from Germany?

PubMed

Zhu, Yan; Balke, Klaus-Dieter

2008-03-01

For drinking water security the German waterworks proceed on a comprehensive concept, i.e., the protection of all the regions from the recharge area to the client. It includes the protection of the recharge area by a precautionary management, a safe water treatment, a strict maintenance of the water distribution network, continuous control and an intensive training of staff. Groundwater protection zones together with effective regulations and control play a very important role. Three protection zones with different restrictions in land-use are distinguished. Water in reservoirs and lakes is also protected by Surface Water Protection Zones. Within the surrounding area the land-use is controlled, too. Special treatment is necessary if acidification happens caused by acid rain, or eutrophication caused by the inflow of sewage. Very important is the collaboration between waterworks and the farmers cultivating land in the recharge area in order to execute water-protecting ecological farming with the aim to reduce the application of fertilizers and plant protection agents. Probable financial losses have to be compensated by the waterworks.

Efficacy of antidotes (midazolam, atropine and HI-6) on nerve agent induced molecular and neuropathological changes

PubMed Central

2014-01-01

Background Recent alleged attacks with nerve agent sarin on civilians in Syria indicate their potential threat to both civilian and military population. Acute nerve agent exposure can cause rapid death or leads to multiple and long term neurological effects. The biochemical changes that occur following nerve agent exposure needs to be elucidated to understand the mechanisms behind their long term neurological effects and to design better therapeutic drugs to block their multiple neurotoxic effects. In the present study, we intend to study the efficacy of antidotes comprising of HI-6 (1-[[[4-(aminocarbonyl)-pyridinio]-methoxy]-methyl]-2-[(hydroxyimino) methyl] pyridinium dichloride), atropine and midazolam on soman induced neurodegeneration and the expression of c-Fos, Calpain, and Bax levels in discrete rat brain areas. Results Therapeutic regime consisting of HI-6 (50 mg/kg, i.m), atropine (10 mg/kg, i.m) and midazolam (5 mg/kg, i.m) protected animals against soman (2 × LD50, s.c) lethality completely at 2 h and 80% at 24 h. HI-6 treatment reactivated soman inhibited plasma and RBC cholinesterase up to 40%. Fluoro-Jade B (FJ-B) staining of neurodegenerative neurons showed that soman induced significant necrotic neuronal cell death, which was reduced by this antidotal treatment. Soman increased the expression of neuronal proteins including c-Fos, Bax and Calpain levels in the hippocampus, cerebral cortex and cerebellum regions of the brain. This therapeutic regime also reduced the soman induced Bax, Calpain expression levels to near control levels in the different brain regions studied, except a mild induction of c-Fos expression in the hippocampus. Conclusion Rats that received antidotal treatment after soman exposure were protected from mortality and showed reduction in the soman induced expression of c-Fos, Bax and Calpain and necrosis. Results highlight the need for timely administration of better antidotes than standard therapy in order to prevent the molecular and biochemical changes and subsequent long term neurological effects induced by nerve agents. PMID:24708580

Preparation of UV-protective kefiran/nano-ZnO nanocomposites: physical and mechanical properties.

PubMed

Shahabi-Ghahfarrokhi, Iman; Khodaiyan, Faramarz; Mousavi, Mohammad; Yousefi, Hossein

2015-01-01

In this study, we investigated the effect of ZnO nanoparticles (ZN) as a UV-protective agent of kefiran biopolymers. Our results showed that with increasing ZN content, the tensile strength, elongation at break, and tensile energy to break the kefiran film and nanocomposites also increased. Kefiran nanocomposites with a ZN content higher than 2% produced a UV-protective film with good visual properties, low sensibility to water, and low water-vapor permeability. The thermal properties of all specimens, analyzed by DSC, showed that the ZN content had a negative effect on Tg and a positive effect on nanocomposites' melting point. TEM, SEM micrography and XRD spectrum analysis confirmed the hypothesis that ZNs act like a ball bearing, making movement of kefiran chains easier and increasing elongation at break, while simultaneously decreasing the Tg of kefiran nanocomposites. Copyright © 2014 Elsevier B.V. All rights reserved.

Radiation countermeasure agents: an update (2011 – 2014)

PubMed Central

Newman, Victoria L; Romaine, Patricia LP; Wise, Stephen Y; Seed, Thomas M

2014-01-01

Introduction Despite significant scientific advances over the past 60 years towards the development of a safe, nontoxic and effective radiation countermeasure for the acute radiation syndrome (ARS), no drug has been approved by the US FDA. A radiation countermeasure to protect the population at large from the effects of lethal radiation exposure remains a significant unmet medical need of the US citizenry and, thus, has been recognized as a high priority area by the government. Area covered This article reviews relevant publications and patents for recent developments and progress for potential ARS treatments in the area of radiation countermeasures. Emphasis is placed on the advanced development of existing agents since 2011 and new agents identified as radiation countermeasure for ARS during this period. Expert opinion A number of promising radiation countermeasures are currently under development, seven of which have received US FDA investigational new drug status for clinical investigation. Four of these agents, CBLB502, Ex-RAD, HemaMax and OrbeShield, are progressing with large animal studies and clinical trials. G-CSF has high potential and well-documented therapeutic effects in countering myelosuppression and may receive full licensing approval by the US FDA in the future. PMID:25315070

Evaluation of skin surface hydration state and barrier function of stratum corneum of dorsa of hands and heels treated with PROTECT X2 skin protective cream.

PubMed

Kubota, Takahiro

2012-06-01

Skin roughness is a term commonly used in Japan to describe a poor skin condition related to a rough and dry skin surface that develops as a result of various damaging effects from the environment or skin inflammation. Recovery from skin roughness requires skin care for a long period, thus it is important to prevent development of such skin changes. PROTECT X2 contains agents used for a protective covering of the skin from frequent hand washing or use of alcohol-based disinfectants. These unique components are also thought to be effective to treat skin roughness of the dorsa of the hands and heels. In the present study, we evaluated the effectiveness of PROTECT X2 to increase skin surface hydration state, as well as enhance the barrier function of the stratum corneum of the dorsa of the hands and heels in elderly individuals. A total of 8 elderly subjects and their caretakers without any skin diseases participated in the study. They applied PROTECT X2 by themselves to the dorsum area of 1 hand and heel 3 to 5 times daily for 1 month, while the opposite sides were left untreated. We measured stratum corneum (SC) hydration and transepidermal water loss (TEWL) before beginning treatment, then 1 week and 1 month after the start of treatment to compare between the treated and untreated skin. SC hydration state after applications of PROTECT X2 was 1.5- to 3.0-fold higher than that of the untreated skin in the dorsa of both hands and heels, indicating that the moisturizing ingredients accompanied by water were replenished in those areas where the cream was applied. Also, TEWL in the dorsum of the hands was 17.0-27.9% lower on the treated side, indicating improvement in SC barrier function. On the basis of these findings, we concluded that PROTECT X2 enhances water-holding in the SC and aids the barrier function of the skin in the dorsum of the hands. In addition, we consider that this formulation is useful for not only protecting the hands from the effects of such agents as detergents and alcohol-based disinfectants, but also for protecting heel skin covered by a thick SC from dry and cold conditions such as those encountered in winter. However, since the SC in that area is much thicker than that of the hands, the barrier function was not significantly improved within 1 month of daily treatments.

Kunkel Lecture: Fundamental immunodeficiency and its correction

PubMed Central

2017-01-01

“Fundamental immunodeficiency” is the inability of the encoded immune system to protect an otherwise healthy host from every infection that could threaten its life. In contrast to primary immunodeficiencies, fundamental immunodeficiency is not rare but nearly universal. It results not from variation in a given host gene but from the rate and extent of variation in the genes of other organisms. The remedy for fundamental immunodeficiency is “adopted immunity,” not to be confused with adaptive or adoptive immunity. Adopted immunity arises from four critical societal contributions to the survival of the human species: sanitation, nutrition, vaccines, and antimicrobial agents. Immunologists have a great deal to contribute to the development of vaccines and antimicrobial agents, but they have focused chiefly on vaccines, and vaccinology is thriving. In contrast, the effect of antimicrobial agents in adopted immunity, although fundamental, is fragile and failing. Immunologists can aid the development of sorely needed antimicrobial agents, and the study of antimicrobial agents can help immunologists discover targets and mechanisms of host immunity. PMID:28701368

Andrographis paniculata Diterpenoids Protect against Radiation-Induced Transformation in BALB/3T3 Cells.

PubMed

Nantajit, Danupon; Jetawattana, Suwimol; Suriyo, Tawit; Grdina, David J; Satayavivad, Jutamaad

2017-07-01

One of the most concerning side effects of exposure to radiation are the carcinogenic risks. To reduce the negative effects of radiation, both cytoprotective and radioprotective agents have been developed. However, little is known regarding their potential for suppressing carcinogenesis. Andrographis paniculata , a plant, with multiple medicinal uses that is commonly used in traditional medicine, has three major constituents known to have cellular antioxidant activity: andrographolide (AP1); 14-deoxy-11,12-didehydroandrographolide (AP3); and neoandrographolide (AP4). In our study, we tested these elements for their radioprotective properties as well as their anti-neoplastic effects on transformation using the BALB/3T3 cell model. All three compounds were able to reduce radiation-induced DNA damage. However, AP4 appeared to have superior radioprotective properties compared to the other two compounds, presumably by protecting mitochondrial function. The compound was able to suppress radiation-induced cellular transformation through inhibition of STAT3. Treatment with AP4 also reduced expressions of MMP-2 and MMP-9. These results suggest that AP4 could be further studied and developed into an anti-transformation/carcinogenic drug as well as a radioprotective agent.

Microencapsulation of Self Healing Agents for Corrosion Control Coatings

NASA Technical Reports Server (NTRS)

Jolley, S. T.; Li, W.; Buhrow, J. W.; Calle, L. M.

2011-01-01

Corrosion, the environmentally induced degradation of materials, is a very costly problem that has a major impact on the global economy. Results from a 2-year breakthrough study released in 2002 by the U.S. Federal Highway Administration (FHWA) showed that the total annual estimated direct cost associated with metallic corrosion in nearly every U.S. industry sector was a staggering $276 billion, approximately 3.1% of the nation's Gross Domestic Product (GOP). Corrosion protective coatings are widely used to protect metallic structures from the detrimental effects of corrosion but their effectiveness can be seriously compromised by mechanical damage, such as a scratch, that exposes the metallic substrate. The incorporation of a self healing mechanism into a corrosion control coating would have the potential to significantly increase its effectiveness and useful lifetime. This paper describes work performed to incorporate a number of microcapsule-based self healing systems into corrosion control coatings. The work includes the preparation and evaluation of self-healing systems based on curable epoxy, acrylate, and siloxane resins, as well as, microencapsulated systems based on passive, solvent born, healing agent delivery. The synthesis and optimization of microcapsule-based self healing systems for thin coating (less than 100 micron) will be presented.

Agent selection and protective effects during single droplet drying of bacteria.

PubMed

Khem, Sarim; Woo, Meng Wai; Small, Darryl M; Chen, Xiao Dong; May, Bee K

2015-01-01

The protective mechanisms of whey protein isolate (WPI), trehalose, lactose, and skim milk on Lactobacillus plantarum A17 during convective droplet drying has been explored. A single droplet drying technique was used to monitor cell survival, droplet temperature and corresponding changes in mass. WPI and skim milk provided the highest protection amongst the materials tested. In situ analysis of the intermediate stage of drying revealed that for WPI and skim milk, crust formation reduces the rate of sudden temperature increase thereby imparting less stress on the cells. Irreversible denaturation of the WPI components might have also contributed to the protection of the cells. Skim milk, however, 'loses' the protective behaviour towards the latter stages of drying. This indicates that the concentration of the WPI components could be another possible factor determining the sustained protective behaviour during the later stages of drying when the moisture content is low. Copyright © 2014 Elsevier Ltd. All rights reserved.

Development of vaccines for bio-warfare agents.

PubMed

Rosenthal, S R; Clifford, J C M

2002-01-01

There is a recognized need for the development of new vaccines (as well as other biologicals and drugs) to counteract the effects of a potential bio-terrorist or bio-warfare event in the U.S. domestic population and military forces. Regulation of products to protect against potential bio-warfare agents poses unique challenges since the usual measures of efficacy that require exposure to natural disease may not currently be possible, for epidemiological and ethical reasons. To help to address this issue, the FDA has published and requested comments on a proposed animal rule intended to address certain efficacy issues for new agents for use against lethal or permanently disabling toxic substances. Recent product development activity has focused on Bacillus anthracis (anthrax) and variola major (smallpox), agents that are regarded as highest priority in posing a risk to national security. FDA resources exist to assist vaccine developers with regard to the novel challenges posed in the dinical development of these products.

ELEVATED HSP70 STIMULATES CELL PROLIFERATION AND IS CYTOPROTECTIVE AGAINST HEAT AND VINCRISTINE TOXICITY IN MCF-7 CELLS.

EPA Science Inventory

Heat-shock proteins (HSPs) play important roles in regulating cell growth and protecting cells from adverse effects of heat and chemical stress. In many types of cancer, elevated HSP70 levels are associated with poor prognosis and resistance to chemotherapeutic agents. In the pre...

INHIBITION OF FRIED MEAT-INDUCED DNA DAMAGE: A DIETARY INTERVENTION STUDY IN HUMANS

EPA Science Inventory

Dietary exposures have been implicated as risk factors in colorectal cancer. Such agents may act by causing DNA damage or may be protective against DNA damage. The effects of dietary exposures in causing or preventing damage have not been assessed directly in colon tissues. In th...

Protective effects of Aloe vera-based diets in Eimeria maxima-infected broiler chickens

USDA-ARS?s Scientific Manuscript database

Aloes have been widely used for a broad range of pharmacological activities, including parasitic problems. Avian coccidiosis is the most costly and wide-spread parasitic disease in the poultry industry, and has been mainly controlled by the use of chemotherapeutic agents. Due to the emergence of dru...

Development of vaccines against pertussis caused by Bordetella holmesii using a mouse intranasal challenge model.

PubMed

Saito, Momoko; Odanaka, Keita; Otsuka, Nao; Kamachi, Kazunari; Watanabe, Mineo

2016-09-01

Bordetella holmesii is recognized as the third causative agent of pertussis (whooping cough) in addition to Bordetella pertussis and Bordetella parapertussis. Pertussis caused by B. holmesii is not rare around the world. However, to date, there is no effective vaccine against B. holmesii. We examined the protective potency of pertussis vaccines available in Japan and vaccines prepared from B. holmesii. A murine model of respiratory infection was exploited to evaluate protective potency. No Japanese commercial pertussis vaccines were effective against B. holmesii. In contrast, a wBH vaccine and an aBH vaccine prepared from B. holmesii were both protective. Passive immunization with sera from mice immunized with aBH vaccine established protection against B. holmesii, indicating that B. holmesii-specific serum antibodies might play an important role in protection. Immuno-proteomic analysis with sera from mice immunized with aBH vaccine revealed that the sera recognized a BipA-like protein of B. holmesii. An aBH vaccine prepared from a BipA-like protein-deficient mutant strain did not have a protective effect against B. holmesii. Taken together, our results suggest that the BipA-like protein plays an important role in the protective efficacy of aBH vaccine. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

Myeloid cell leukaemia 1 has a vital role in retinoic acid-mediated protection of Toll-like receptor 9-stimulated B cells from spontaneous and DNA damage-induced apoptosis.

PubMed

Holm, Kristine L; Indrevaer, Randi L; Myklebust, June Helen; Kolstad, Arne; Moskaug, Jan Øivind; Naderi, Elin H; Blomhoff, Heidi K

2016-09-01

Vitamin A is an essential anti-infective agent with pleiotropic effects on cells of the immune system. The goal of the present study was to unravel the impact of the vitamin A metabolite retinoic acid (RA) on B-cell survival related both to normal B-cell homeostasis and to the detrimental effects imposed by DNA-damaging agents. By combining RA with Toll-like receptor 9 (TLR9) ligands, we show that RA prevents spontaneous, irradiation- and doxorubicin-induced apoptosis of human B cells in an RA receptor-dependent manner. RA-mediated survival involved up-regulation of the anti-apoptotic protein myeloid cell leukemia 1 (MCL1) at the transcriptional level, and knock down of MCL1 by small interfering RNA partially reversed the effects of RA. To ensure that the combination of TLR9-ligands and RA would not promote the survival of malignant B cells, the combined effects of stimulation with RA and TLR9 ligands was assessed on cells from patients with B-cell malignancies. In contrast to the effects on normal B cells, the combination of TLR9 stimulation and RA neither enhanced the MCL1 levels nor inhibited the death of malignant B cells challenged by DNA-damaging agents. Taken together, the present results reveal a vital role of MCL1 in RA-mediated survival of normal B cells. Moreover, the findings suggest that RA in combination with TLR9 ligands might be useful adjuvants in the treatment of B-cell malignancies by selectively protecting normal and not malignant B cells from DNA-damage-induced cell death. © 2016 John Wiley & Sons Ltd.

Point: From animal models to prevention of colon cancer. Systematic review of chemoprevention in min mice and choice of the model system.

PubMed

Corpet, Denis E; Pierre, Fabrice

2003-05-01

The Apc(Min/+) mouse model and the azoxymethane (AOM) rat model are the main animal models used to study the effect of dietary agents on colorectal cancer. We reviewed recently the potency of chemopreventive agents in the AOM rat model (D. E. Corpet and S. Tache, Nutr. Cancer, 43: 1-21, 2002). Here we add the results of a systematic review of the effect of dietary and chemopreventive agents on the tumor yield in Min mice. The review is based on the results of 179 studies from 71 articles and is displayed also on the internet http://corpet.net/min.(2) We compared the efficacy of agents in the Min mouse model and the AOM rat model, and found that they were correlated (r = 0.66; P < 0.001), although some agents that afford strong protection in the AOM rat and the Min mouse small bowel increase the tumor yield in the large bowel of mutant mice. The agents included piroxicam, sulindac, celecoxib, difluoromethylornithine, and polyethylene glycol. The reason for this discrepancy is not known. We also compare the results of rodent studies with those of clinical intervention studies of polyp recurrence. We found that the effect of most of the agents tested was consistent across the animal and clinical models. Our point is thus: rodent models can provide guidance in the selection of prevention approaches to human colon cancer, in particular they suggest that polyethylene glycol, hesperidin, protease inhibitor, sphingomyelin, physical exercise, epidermal growth factor receptor kinase inhibitor, (+)-catechin, resveratrol, fish oil, curcumin, caffeate, and thiosulfonate are likely important preventive agents.

Neuroprotective Effects of Galantamine on Nerve Agent-Induced Neuroglial and Biochemical Changes.

PubMed

Golime, RamaRao; Palit, Meehir; Acharya, J; Dubey, D K

2018-05-01

Neuroprotection from nerve agent such as soman-induced neural damage is a major challenge for existing drugs. Nerve agent exposure can cause many neural effects in survivors arising mainly due to acetylcholinesterase (AChE) inhibition or death within minutes. Unraveling the mechanisms underlying the nerve agent-induced multiple neurological effects is useful to develop better and safe drugs. The present study aimed to understand the molecular response during soman exposure and to evaluate the neuroprotective efficacy of galantamine on nerve agent-induced neurotoxic changes. mRNA expression studies using quantitative real-time PCR revealed significant changes in S-100β, Gfap, c-fos, and Bdnf in the hippocampus and piriform cortex after soman (90 μg/kg, s.c) exposure. Immunoblot analysis showed acute soman exposure significantly increased the protein levels of neuroglial markers (S100-β and GFAP); c-Fos and protein oxidation in discrete rat brain areas indicate their role in nerve agent-induced neurotoxicity. Induction of BDNF levels during soman exposure may indicate the recovery mechanisms activation. AChE was inhibited in the blood and brain up to 82% after soman exposure. Antidotal treatment with galantamine alone (3 mg/kg) and galantamine plus atropine (10 mg/kg) has protected animals from nerve agent-induced intoxication, death, and soman-inhibited AChE up to 45% in the blood and brain. Animal received galantamine displayed increased levels of neuroprotective genes (nAChRα-7, Bcl-2, and Bdnf) in the brain suggest the neuroprotective value of galantamine. Neuroglial changes, c-Fos, and protein oxidation levels significantly reduced after galantamine and galantamine plus atropine treatment indicate their potential antidotal value in nerve agent treatment.

The Fate of Chemical Warfare Agents in the Environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Talmage, Sylvia Smith; Munro, Nancy B; Watson, Annetta Paule

2007-01-01

Chemical Warfare Agents, Second Edition has been totally revised since the successful first edition and expanded to about three times the length, with many new chapters and much more in-depth consideration of all the topics. The chapters have been written by distinguished international experts in various aspects of chemical warfare agents and edited by an experienced team to produce a clear review of the field. The book now contains a wealth of material on the mechanisms of action of the major chemical warfare agents, including the nerve agent cyclosarin, formally considered to be of secondary importance, as well as ricinmore » and abrin. Chemical Warfare Agents, Second Edition discusses the physico-chemical properties of chemical warfare agents, their dispersion and fate in the environment, their toxicology and management of their effects on humans, decontamination and protective equipment. New chapters cover the experience gained after the use of sarin to attack travelers on the Tokyo subway and how to deal with the outcome of the deployment of riot control agents such as CS gas. This book provides a comprehensive review of chemical warfare agents, assessing all available evidence regarding the medical, technical and legal aspects of their use. It is an invaluable reference work for physicians, public health planners, regulators and any other professionals involved in this field.« less

Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity.

PubMed

Benavente-García, O; Castillo, J

2008-08-13

Significantly, much of the activity of Citrus flavonoids appears to impact blood and microvascular endothelial cells, and it is not surprising that the two main areas of research on the biological actions of Citrus flavonoids have been inflammation and cancer. Epidemiological and animal studies point to a possible protective effect of flavonoids against cardiovascular diseases and some types of cancer. Although flavonoids have been studied for about 50 years, the cellular mechanisms involved in their biological action are still not completely known. Many of the pharmacological properties of Citrus flavonoids can be linked to the abilities of these compounds to inhibit enzymes involved in cell activation. Attempts to control cancer involve a variety of means, including the use of suppressing, blocking, and transforming agents. Suppressing agents prevent the formation of new cancers from procarcinogens, and blocking agents prevent carcinogenic compounds from reaching critical initiation sites, while transformation agents act to facilitate the metabolism of carcinogenic components into less toxic materials or prevent their biological actions. Flavonoids can act as all three types of agent. Many epidemiological studies have shown that regular flavonoid intake is associated with a reduced risk of cardiovascular diseases. In coronary heart disease, the protective effects of flavonoids include mainly antithrombotic, anti-ischemic, anti-oxidant, and vasorelaxant. It is suggested that flavonoids decrease the risk of coronary heart disease by three major actions: improving coronary vasodilatation, decreasing the ability of platelets in the blood to clot, and preventing low-density lipoproteins (LDLs) from oxidizing. The anti-inflammatory properties of the Citrus flavonoids have also been studied. Several key studies have shown that the anti-inflammatory properties of Citrus flavonoids are due to its inhibition of the synthesis and biological activities of different pro-inflammatory mediators, mainly the arachidonic acid derivatives, prostaglandins E 2, F 2, and thromboxane A 2. The anti-oxidant and anti-inflammatory properties of Citrus flavonoids can play a key role in their activity against several degenerative diseases and particularly brain diseases. The most abundant Citrus flavonoids are flavanones, such as hesperidin, naringin, or neohesperidin. However, generally, the flavones, such as diosmin, apigenin, or luteolin, exhibit higher biological activity, even though they occur in much lower concentrations. Diosmin and rutin have a demonstrated activity as a venotonic agent and are present in several pharmaceutical products. Apigenin and their glucosides have been shown a good anti-inflammatory activity without the side effects of other anti-inflammatory products. In this paper, we discuss the relation between each structural factor of Citrus flavonoids and the anticancer, anti-inflammatory, and cardiovascular protection activity of Citrus flavonoids and their role in degenerative diseases.

[Use of guinea pigs to evaluate the efficacy of a heterological immunoglobulin against Bolivian hemorrhagic fever].

PubMed

Khmelev, A L; Borisevich, I V; Pantiukhov, V B; Pirozhkov, A P; Syromiatnikova, S I; Shatokhina, I V; Mel'nikov, S A; Shagarov, E E

2009-01-01

The use of guinea pigs as a laboratory model was proven to be appropriate in investigating the protective properties of a heterological immunoglobulin against Bolivian hemorrhagic fever at the preclinical stage of the study. A highly pathogenic Machupo virus strain that caused guinea pigs' death with respect with an agent's dose was cultivated. Injection of 1.0 ml of the immunoglobulin provided a 100% protective effect for the guinea pigs infected with the highly pathogenic Machupo virus strain in a dose of 10 LD50.

Chemical form of selenium differentially influences DNA repair pathways following exposure to lead nitrate.

PubMed

McKelvey, Shauna M; Horgan, Karina A; Murphy, Richard A

2015-01-01

Lead, an environmental toxin is known to induce a broad range of physiological and biochemical dysfunctions in humans through a number of mechanisms including the deactivation of antioxidants thus leading to generation of reactive oxygen species (ROS) and subsequent DNA damage. Selenium on the other hand has been proven to play an important role in the protection of cells from free radical damage and oxidative stress, though its effects are thought to be form and dose dependent. As the liver is the primary organ required for metabolite detoxification, HepG2 cells were chosen to assess the protective effects of various selenium compounds following exposure to the genotoxic agent lead nitrate. Initially DNA damage was quantified using a comet assay, gene expression patterns associated with DNA damage and signalling were also examined using PCR arrays and the biological pathways which were most significantly affected by selenium were identified. Interestingly, the organic type selenium compounds (selenium yeast and selenomethionine) conferred protection against lead induced DNA damage in HepG2 cells; this is evident by reduction in the quantity of DNA present in the comet tail of cells cultured in their presence with lead. This trend also followed through the gene expression changes noted in DNA damage pathways analysed. These results were in contrast with those of inorganic sodium selenite which promoted lead induced DNA damage evident in both the comet assay results and the gene expression analysis. Over all this study provided valuable insights into the effects which various selenium compounds had on the DNA damage and signalling pathway indicating the potential for using organic forms of selenium such as selenium enriched yeast to protect against DNA damaging agents. Copyright © 2014 Elsevier GmbH. All rights reserved.

Stoichiometric and catalytic scavengers as protection against nerve agent toxicity: a mini review.

PubMed

Lenz, David E; Yeung, David; Smith, J Richard; Sweeney, Richard E; Lumley, Lucille A; Cerasoli, Douglas M

2007-04-20

Currently fielded treatments for nerve agent intoxication promote survival, but do not afford complete protection against either nerve agent-induced motor and cognitive deficits or neuronal pathology. The use of human plasma-derived butyrylcholinesterase (HuBuChE) to neutralize the toxic effects of nerve agents in vivo has been shown to both aid survival and protect against decreased cognitive function after nerve agent exposure. Recently, a commercially produced recombinant form of human butyrylcholinesterase (r-HuBuChE; PharmAthene Inc.) expressed in the milk of transgenic goats has become available. This material is biochemically similar to plasma-derived HuBuChE in in vitro assays. The pharmacokinetic characteristics of a polyethylene glycol coated (pegylated) form of r-HuBuChE were determined in guinea pigs; the enzyme was rapidly bioavailable with a half-life (t(1/2)) and pharmacokinetic profile that resembled that of plasma-derived huBuChE. Guinea pigs were injected with 140mg/kg (i.m.) of pegylated r-HuBuChE 18h prior to exposure (sc) to 5.5xLD(50) VX or soman. VX and soman were administered in a series of three injections of 1.5xLD(50), 2.0xLD(50), and 2.0xLD(50), respectively, with injections separated by 2h. Pretreatment with pegylated r-HuBuChE provided 100% survival against multiple lethal doses of VX and soman. Guinea pigs displayed no signs of nerve agent toxicity following exposure. Assessments of motor activity, coordination, and acquisition of spatial memory were performed for 2 weeks following nerve agent exposure. There were no measurable decreases in motor or cognitive function during this period. In contrast, animals receiving 1.5xLD(50) challenges of soman or VX and treated with standard atropine, 2-PAM, and diazepam therapy showed 50 and 100% survival, respectively, but exhibited marked decrements in motor function and, in the case of GD, impaired spatial memory acquisition. The advances in this field have resulted in the decision to select both the plasma-derived and the recombinant form of BuChE for advanced development and transition to clinical trials. Efforts have now been expanded to identify a catalytic protein capable of not only binding, but also rapidly hydrolyzing the standard threat nerve agents. Recent work has focused on paraoxonase-1 (PON1), a naturally occurring human serum enzyme with the capacity to catalyze the hydrolysis of nerve agents, albeit too slowly to afford dramatic protection. Using rational design, several amino acids involved in substrate binding have been identified and site-directed mutations have revealed that residue H115 plays an important role in binding. In addition, the stereospecificity of PON1 for the catalytic hydrolysis of soman has been examined. The enzyme exhibits a slight stereospecificity for the C+P+ isomer of soman, which is due more to preferential binding than to selective hydrolysis of this isomer. The results suggest that it may be possible to engineer a mutant form of PON1 with enhanced activity and stereospecificity for the most toxic nerve agent isoforms.

[Microflora of damaged ferroconcrete structures under the conditions of inhibitory protection].

PubMed

Kopteva, Zh P; Zanina, V V; Purish, L M; Piliashenko-Novokhatnyĭ, A I; Kozlova, I A

2004-01-01

Thionic, sulphate-reducing, denitrifying and ammonifying bacteria widely distributed in the sewer system on various structure elements have been isolated from damaged ferroconcrete samples. Effect of protective materials on microbe-induced corrosion of metal famework of concrete samples has been studied. Selective effect of corrosion inhibitors and coatings on the growth of corrosion-active bacteria of sulphur and nitrogen cycle has been revealed. It is shown that acid medium formed by thionic bacteria is more aggressive than ammonium-hydrosulphide one formed by denitrifying and sulphate-reducing bacteria. It has been established that the corrosion inhibitor--pyrquin, organosilicon coating CO-FMI and epoxyorganosilicon coating 4sk are most effective materials as to the action of thionic bacteria--dangerous agents of ferroconcrete aerobic corrosion.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milatovic, Dejan, E-mail: dejan.milatovic@vanderbilt.edu; Gupta, Ramesh C.; Yu, Yingchun

Exposure to excessive manganese (Mn) levels leads to neurotoxicity, referred to as manganism, which resembles Parkinson's disease (PD). Manganism is caused by neuronal injury in both cortical and subcortical regions, particularly in the basal ganglia. The basis for the selective neurotoxicity of Mn is not yet fully understood. However, several studies suggest that oxidative damage and inflammatory processes play prominent roles in the degeneration of dopamine-containing neurons. In the present study, we assessed the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates and associated neuronal dysfunctions both in vitro and in vivo. Results from ourmore » in vitro study showed a significant (p < 0.01) increase in biomarkers of oxidative damage, F{sub 2}-isoprostanes (F{sub 2}-IsoPs), as well as the depletion of ATP in primary rat cortical neurons following exposure to Mn (500 {mu}M) for 2 h. These effects were protected when neurons were pretreated for 30 min with 100 of an antioxidant, the hydrophilic vitamin E analog, trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), or an anti-inflammatory agent, indomethacin. Results from our in vivo study confirmed a significant increase in F{sub 2}-IsoPs levels in conjunction with the progressive spine degeneration and dendritic damage of the striatal medium spiny neurons (MSNs) of mice exposed to Mn (100 mg/kg, s.c.) 24 h. Additionally, pretreatment with vitamin E (100 mg/kg, i.p.) or ibuprofen (140 {mu}g/ml in the drinking water for two weeks) attenuated the Mn-induced increase in cerebral F{sub 2}-IsoPs? and protected the MSNs from dendritic atrophy and dendritic spine loss. Our findings suggest that the mediation of oxidative stress/mitochondrial dysfunction and the control of alterations in biomarkers of oxidative injury, neuroinflammation and synaptodendritic degeneration may provide an effective, multi-pronged therapeutic strategy for protecting dysfunctional dopaminergic transmission and slowing of the progression of Mn-induced neurodegenerative processes. -- Research highlights: Black-Right-Pointing-Pointer Mn exposure leads to neurotoxicity in vitro and in vivo. Black-Right-Pointing-Pointer Antioxidants and anti-inflammatory agents attenuate Mn-induced oxidative injury. Black-Right-Pointing-Pointer These agents also protect the striatal neurons from dendritic atrophy and spine loss. Black-Right-Pointing-Pointer These prophylactic strategies may be effective against Mn neurotoxicity.« less

Ultra-Fast Degradation of Chemical Warfare Agents Using MOF-Nanofiber Kebabs.

PubMed

Zhao, Junjie; Lee, Dennis T; Yaga, Robert W; Hall, Morgan G; Barton, Heather F; Woodward, Ian R; Oldham, Christopher J; Walls, Howard J; Peterson, Gregory W; Parsons, Gregory N

2016-10-10

The threat associated with chemical warfare agents (CWAs) motivates the development of new materials to provide enhanced protection with a reduced burden. Metal-organic frame-works (MOFs) have recently been shown as highly effective catalysts for detoxifying CWAs, but challenges still remain for integrating MOFs into functional filter media and/or protective garments. Herein, we report a series of MOF-nanofiber kebab structures for fast degradation of CWAs. We found TiO 2 coatings deposited via atomic layer deposition (ALD) onto polyamide-6 nanofibers enable the formation of conformal Zr-based MOF thin films including UiO-66, UiO-66-NH 2 , and UiO-67. Cross-sectional TEM images show that these MOF crystals nucleate and grow directly on and around the nanofibers, with strong attachment to the substrates. These MOF-functionalized nanofibers exhibit excellent reactivity for detoxifying CWAs. The half-lives of a CWA simulant compound and nerve agent soman (GD) are as short as 7.3 min and 2.3 min, respectively. These results therefore provide the earliest report of MOF-nanofiber textile composites capable of ultra-fast degradation of CWAs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

TVP1022 and propargylamine protect neonatal rat ventricular myocytes against doxorubicin-induced and serum starvation-induced cardiotoxicity.

PubMed

Kleiner, Yana; Bar-Am, Orit; Amit, Tamar; Berdichevski, Alexandra; Liani, Esti; Maor, Gila; Reiter, Irina; Youdim, Moussa B H; Binah, Ofer

2008-09-01

We recently reported that propargylamine derivatives such as rasagiline (Azilect) and its S-isomer TVP1022 are neuroprotective. The aim of this study was to test the hypothesis that the neuroprotective agents TVP1022 and propargylamine (the active moiety of propargylamine derivatives) are also cardioprotective. We specifically investigated the protective efficacy of TVP1022 and propargylamine in neonatal rat ventricular myocytes (NRVM) against apoptosis induced by the anthracycline chemotherapeutic agent doxorubicin and by serum starvation. We demonstrated that pretreatment of NRVM cultures with TVP1022 or propargylamine attenuated doxorubicin-induced and serum starvation-induced apoptosis, inhibited the increase in cleaved caspase 3 levels, and reversed the decline in Bcl-2/Bax ratio. These cytoprotective effects were shown to reside in the propargylamine moiety. Finally, we showed that TVP1022 neither caused proliferation of the human cancer cell lines HeLa and MDA-231 nor interfered with the anti-cancer efficacy of doxorubicin. These results suggest that TVP1022 should be considered as a novel cardioprotective agent against ischemic insults and against anthracycline cardiotoxicity and can be coadministered with doxorubicin in the treatment of human malignancies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foust, C.B.

An incident involving chemical warfare agents requires a unique hazardous materials (HAZMAT) response. As with an HAZMAT event, federal regulations prescribe that responders must be protected from exposure to the chemical agents. But unlike other HAZMAT events, special considerations govern selection of personal protective equipment (PPE). PPE includes all clothing, respirators and monitoring devices used to respond to a chemical release. PPE can differ depending on whether responders are military or civilian personnel.

The impact of renal protection clinics on prescription of and adherence to cardioprotective drug therapy in chronic kidney disease patients.

PubMed

Lepeytre, Fanny; Cardinal, Héloise; Fradette, Lorraine; Verhave, Jacobien; Dorais, Marc; LeLorier, Jacques; Pichette, Vincent; Madore, François

2017-06-01

Background: The aim of this study was to assess the impact of follow-up in renal protection clinics on the prescription of and adherence to cardioprotective drugs in patients with chronic kidney disease (CKD). Methods: We studied stage 4 and 5 CKD patients who initiated follow-up in three renal protection clinics. The prescription pattern of antihypertensive agents (AHA) and lipid-lowering agents (LLAs) was measured as the percentage of patients who are prescribed the agents of interest at a given time. Adherence to drug therapy was defined as the percentage of days, during a pre-defined observation period, in which patients have an on-hand supply of their prescribed medications. Results: A total of 259 CKD patients were enrolled and followed for up to 1 year after referral to renal protection clinics. There was a significant increase in the prescription of angiotensin-converting enzyme inhibitors (34-39%), angiotensin II receptor blockers (11-14%), beta-blockers (40-51%), calcium channel blockers (62-74%), diuretics (66-78%) and LLAs (39-47%) during follow-up in the renal protection clinic compared with baseline (P-values <0.01 for all comparisons). The proportions of patients with good (≥ 80%) and poor (< 80%) adherence to AHA (P = 0.41) and LLAs (P = 0.11) were similar in the year preceding and the year following the first visit to the renal protection clinics. Conclusion: Our results suggest that referral and follow-up in a renal protection clinic may increase the prescription of cardioprotective agents in CKD patients, but does not appear to improve adherence to these medications.

Protective effect of Carica papaya L leaf extract against alcohol induced acute gastric damage and blood oxidative stress in rats.

PubMed

Indran, M; Mahmood, A A; Kuppusamy, U R

2008-09-01

The effects of Carica papaya leaf (CPL) aqueous extract on alcohol induced acute gastric damage and the immediate blood oxidative stress level were studied in rats. The results showed that gastric ulcer index was significantly reduced in rats pretreated with CPL extract as compared with alcohol treated controls. The in vitro studies using 2,2-Diphenyl-1-Picryl-Hydrazyl (DPPH) assay showed strong antioxidant nature of CPL extract. Biochemical analysis indicated that the acute alcohol induced damage is reflected in the alterations of blood oxidative indices and CPL extract offered some protection with reduction in plasma lipid peroxidation level and increased erythrocyte glutathione peroxidase activity. Carica papaya leaf may potentially serve as a good therapeutic agent for protection against gastric ulcer and oxidative stress.

Novel therapy for renal protection.

PubMed

Zarbock, Alexander; Milles, Kindgen

2015-08-01

Acute kidney injury (AKI) is a common and serious complication that significantly increases morbidity, mortality, and cost of care after surgery. In this article, we review recent studies that deal with strategies for renal protection and the prevention of AKI after surgery. A prerequisite for any prophylactic intervention is the identification of patients at risk for AKI or those with acute kidney damage before kidney function deteriorates. In this context, new biomarkers can help to detect cellular injury early. This way, a window for interventions can be opened. Several studies demonstrated the tissue-protective effect of remote ischemic preconditioning in various organs. There is clear evidence that use of balanced crystalloid fluids and the avoidance of hyperchloremic solutions for infusion therapy can reduce the incidence of AKI. Preliminary data show a protective effect if dexmedetomidine is used as a sedative agent following cardiac surgery. The most important intervention with proven efficacy to protect from AKI is aggressive hemodynamic stabilization. Early identification of patients at risk for AKI is crucial to apply any protective intervention. An improved perioperative management is required to prevent AKI. Although pharmacological therapies aiming to protect AKI are under evaluation, hemodynamic optimization and avoidance of nephrotoxic drugs are critical for perioperative patient.

Two classes of anti-platelet drugs reduce anatomical infarct size in monkey hearts.

PubMed

Yang, Xi-Ming; Liu, Yanping; Cui, Lin; Yang, Xiulan; Liu, Yongge; Tandon, Narendra; Kambayashi, Junichi; Downey, James M; Cohen, Michael V

2013-04-01

Recent studies in rabbits have demonstrated that platelet P2Y12 receptor antagonists are cardioprotective, and that the mechanism is surprisingly not related to blockade of platelet aggregation but rather to triggering of the same signal transduction pathway seen in pre- and postconditioning. We wanted to determine whether this same cardioprotection could be documented in a primate model and whether the protection was limited to P2Y12 receptor antagonists or was a class effect. Thirty-one macaque monkeys underwent 90-min LAD occlusion/4-h reperfusion. The platelet P2Y12 receptor blocker cangrelor started just prior to reperfusion significantly decreased infarction by an amount equivalent to that seen with ischemic postconditioning (p < 0.001). For any size of risk zone, infarct size in treated hearts was significantly smaller than that in control hearts. OM2, an investigational murine antibody against the primate collagen receptor glycoprotein (GP) VI, produced similar protection (p < 0.01) suggesting a class effect. Both cangrelor and OM2 were quite effective at blocking platelet aggregation (94 % and 97 %, respectively). Thus in a primate model in which infarct size could be determined directly platelet anti-aggregatory agents are cardioprotective. The important implication of these investigations is that patients with acute myocardial infarction who are treated with platelet anti-aggregatory agents prior to revascularization may already be in a postconditioned state. This hypothesis may explain why in recent clinical trials postconditioning-mimetic interventions which were so protective in animal models had at best only a modest effect.

THE EFFECT OF IONIZING RADIATION ON PREGNANCY AND FETAL DEVELOPMENT (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pobedinskii, N.M.

1961-01-01

A review is presented on the reactions of pregnant animais to radiation, the effect of ionizing radiation on the fetus and offspring of man and animal, the mechanism of the action of ionizing radiation on the fetus, and the protective action of agents such as mercamine and heroin. It is stressed that the effect of a dose of ionizing radiation varies with the stage of pregnancy at the time of irradiation (80 references). (TTT)

Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution.

PubMed

Suzuki, Takahiro; Yoshida, Norimasa; Nakabe, Nami; Isozaki, Yutaka; Kajikawa, Hirokazu; Takagi, Tomohisa; Handa, Osamu; Kokura, Satoshi; Ichikawa, Hiroshi; Naito, Yuji; Matsui, Hirofumi; Yoshikawa, Toshikazu

2008-03-01

Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and anti-inflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats. In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated (twice daily for 3 days) treatment than single treatment before aspirin administration. Immunostaining of zonula occludens (ZO)-1, one of the tight junctional proteins, was strengthened in rat gastric mucosa after repeated administration of rebamipide. In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM-1. Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.

Exploring the protective effects of calcium-containing carrier against drying-induced cellular injuries of probiotics using single droplet drying technique.

PubMed

Zheng, Xufeng; Fu, Nan; Huang, Song; Jeantet, Romain; Chen, Xiao Dong

2016-12-01

Protective carriers that encapsulate probiotics in spray drying could improve the survival ratio of dried cells through different mechanisms. Unveiling the protective mechanism of each carrier will contribute to a rational design of high performance carrier formulation. This study utilized single droplet drying (SDD) technique to investigate the effects of calcium cation in varied carrier formulation. Inactivation histories of Lactobacillus rhamnosus GG (LGG) in different carriers were compared, and cellular injury history of probiotics during droplet drying was studied for the first time. Adding 1mM CaCl 2 to lactose carrier protected cell viability, mitigated cellular injuries, and enhanced regrowth capability as drying progressed, demonstrating the positive effect of Ca 2+ with possible mechanism of stabilizing sub-cellular structures. At later drying stages, cell survival in Lac/Ca carrier was increased by 0.5-1.5 log on selective media compared to lactose carrier. Supplementing calcium-binding agents lowered the protective effect, shortening the initiation of rapid cell inactivation down to 120s of drying. Adding CaCl 2 to trehalose carrier barely improved cell survival, indicating that the protective effect could be influenced by carrier formulation. Pure trehalose carrier exerted excellent protection on LGG, supporting cells to regrow in liquid rich medium even after 180s of drying. The protection of trehalose may stem from stabilization of sub-cellular structures, which possibly overlap the effect of Ca 2+ . The findings suggested that high performance carrier formulation might be developed by combining carrier materials with different protective mechanisms, for maximizing the survival of active dry probiotics in industrial spray drying operation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA-21 expression, Akt and the Bcl-2/Bax pathway

PubMed Central

Ma, Ning; Bai, Jingyun; Zhang, Weihua; Luo, Hong; Zhang, Xin; Liu, Donghai; Qiao, Chenhui

2016-01-01

Trimetazidine is a piperazine-derived metabolic agent, which exerts cell protective effects and has been reported to be efficient in the treatment of chronic stable angina pectoris. In addition, it has been shown to exert protection against acute myocardial infarction. The present study aimed to investigate whether trimetazidine protects against cardiac ischemia/reperfusion (I/R) injury, and to determine whether its curative effects are associated with microRNA (miRNA)-21 expression, Akt, and the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) pathway. Cardiac I/R injury was induced by ligating the left anterior descending coronary artery in adult rats. Subsequently, cardiac function was evaluated, and the expression levels of miRNA-21, Bcl-2, Bax and phosphorylated-Akt were detected using quantitative polymerase chain reaction and western blotting. The results indicated that trimetazidine was able to significantly protect cardiac function and reduce infarct size in rats following cardiac I/R injury. Furthermore, trimetazidine significantly promoted miRNA-21 expression and phosphorylated-Akt protein expression, and reduced the Bcl-2/Bax ratio in rats following cardiac I/R injury. Knockdown of miRNA-21 using anti-miR-21 plasmids was able to reverse the protective effects of trimetazidine against cardiac I/R injury. These results indicated that miRNA-21 serves a protective role in cardiac I/R injury via Akt and the Bcl-2/Bax pathway. In addition, trimetazidine exerts protective effects against cardiac I/R injury through cardiac miRNA-21 expression, Akt, and the Bcl-2/Bax pathway. Therefore, the present study provided evidence regarding the protective effects of miRNA-21 on cardiac I/R injury following treatment with trimetazidine in vivo. PMID:27666568

Protective effect of ferulic acid on cisplatin induced nephrotoxicity in rats.

PubMed

Bami, Erliasa; Ozakpınar, Ozlem Bingol; Ozdemir-Kumral, Zarife Nigar; Köroglu, Kutay; Ercan, Feriha; Cirakli, Zeynep; Sekerler, Turgut; Izzettin, Fikret Vehbi; Sancar, Mesut; Okuyan, Betul

2017-09-01

This study aims to determine the potential protective effects of ferulic acid against cisplatin-induced nephrotoxicity and to compare its effect with curcumin, a well-known protective agent against cisplatin- induced toxicity in rats. Administration of cisplatin resulted in high BUN (Blood Urea Nitrogen), creatinine, MDA (Malondialdehyde), MPO (Myeloperoxidase), TOS (Total Oxidative Status), PtNT (Protein Nitrotyrosine) levels (p<0.05). Histological observations showed abnormal morphology of kidney; in addition with appearance of TUNEL positive cells indicating apoptosis in cisplatin administered group. HO-1 (Heme Oxygenase-1) levels measured by RT-PCR (Real Time Polymerase Chain Reaction), and TAS (Total Antioxidative Status) revealed antioxidant depletion due to cisplatin toxicity in animals (p<0.05). All parameters showed improvement in groups treated with ferulic acid (p<0.05). Ferulic acid treatment was found significant in preventing oxidative stress, increasing antioxidative status and regaining histological parameters to normal, indicating nephroprotective and antioxidant effects of this phenolic compound. Copyright © 2017 Elsevier B.V. All rights reserved.

Selection of the Optimal Herbal Compositions of Red Clover and Pomegranate According to Their Protective Effect against Climacteric Symptoms in Ovariectomized Mice.

PubMed

Kang, Su Jin; Choi, Beom Rak; Kim, Seung Hee; Yi, Hae Yeon; Park, Hye Rim; Song, Chang Hyun; Ku, Sae Kwang; Lee, Young Joon

2016-07-23

This study aimed to ascertain the optimal range of red clover dry extracts (RC) and dried pomegranate concentrate powder (PCP) to induce anti-climacteric effects. Thus, the dose ranges showing protective effect of mixed formulae consisting of RC and PCP were examined in ovariectomized mice. At 28 days after bilateral ovariectomy (OVX), mixed herbal compositions (RC:PCP = 1:1, 1:2, 1:4, 1:8, 2:1, 4:1, and 8:1) were administered orally, at 120 mg/kg once daily for 84 days. We evaluated that RC and PCP mixture attenuate OVX-caused obesity, hyperlipidemia, hepatic steatosis, and osteoporosis. Compared to OVX-induced control mice, body weight and abdominal fat weight in OVX-induced mice were significantly decreased, concomitantly with increase of uterus weight by RC:PCP mixture. Additionally, significant increases in serum estradiol levels were observed in all RC:PCP-treated mice. RC:PCP mixture also showed protective effect against OVX-induced hyperlipidemia, hepatic steatosis. Total body and femur mean bone mineral density (BMD), osteocalcin, bALP contents were effectively increased by RC:PCP mixture. Taken together, RC:PCP mixture (2:1, 1:1, and 4:1) has remarkable protective effects against the changes induced by OVX. In particular, RC:PCP mixture (2:1) shows the strongest effect and may be considered as a potential protective agent against climacteric symptoms.

Selection of the Optimal Herbal Compositions of Red Clover and Pomegranate According to Their Protective Effect against Climacteric Symptoms in Ovariectomized Mice

PubMed Central

Kang, Su Jin; Choi, Beom Rak; Kim, Seung Hee; Yi, Hae Yeon; Park, Hye Rim; Song, Chang Hyun; Ku, Sae Kwang; Lee, Young Joon

2016-01-01

This study aimed to ascertain the optimal range of red clover dry extracts (RC) and dried pomegranate concentrate powder (PCP) to induce anti-climacteric effects. Thus, the dose ranges showing protective effect of mixed formulae consisting of RC and PCP were examined in ovariectomized mice. At 28 days after bilateral ovariectomy (OVX), mixed herbal compositions (RC:PCP = 1:1, 1:2, 1:4, 1:8, 2:1, 4:1, and 8:1) were administered orally, at 120 mg/kg once daily for 84 days. We evaluated that RC and PCP mixture attenuate OVX-caused obesity, hyperlipidemia, hepatic steatosis, and osteoporosis. Compared to OVX-induced control mice, body weight and abdominal fat weight in OVX-induced mice were significantly decreased, concomitantly with increase of uterus weight by RC:PCP mixture. Additionally, significant increases in serum estradiol levels were observed in all RC:PCP-treated mice. RC:PCP mixture also showed protective effect against OVX-induced hyperlipidemia, hepatic steatosis. Total body and femur mean bone mineral density (BMD), osteocalcin, bALP contents were effectively increased by RC:PCP mixture. Taken together, RC:PCP mixture (2:1, 1:1, and 4:1) has remarkable protective effects against the changes induced by OVX. In particular, RC:PCP mixture (2:1) shows the strongest effect and may be considered as a potential protective agent against climacteric symptoms. PMID:27455321

Bacillus amyloliquefaciens subsp. plantarum GR53, a potent biocontrol agent resists Rhizoctonia disease on Chinese cabbage through hormonal and antioxidants regulation.

PubMed

Kang, Sang-Mo; Radhakrishnan, Ramalingam; Lee, In-Jung

2015-10-01

The fungus Rhizoctonia solani is one of the causal agents of numerous diseases that affect crop growth and yield. The aim of this present investigation was to identify a biocontrol agent that acts against R. solani and to determine the agent's protective effect through phytohormones and antioxidant regulation in experimentally infected Chinese cabbage plants. Four rhizospheric soil bacterial isolates GR53, GR169, GR786, and GR320 were tested for their antagonistic activity against R. solani. Among these isolates, GR53 significantly suppressed fungal growth. GR53 was identified as Bacillus amyloliquefaciens subsp. plantarum by phylogenetic analysis of the 16S rDNA sequence. The biocontrol activity of B. amyloliquefaciens subsp. plantarum GR53 was tested in Chinese cabbage plants under controlled conditions. Results showed that R. solani inhibited plant growth (length, width, fresh and dry weight of leaves) by reducing chlorophyll and total phenolic content, as well as by increasing the levels of salicylic acid, jasmonic acid, abscisic acid, and DPPH scavenging activity. By regulating the levels of these compounds, the co-inoculation of B. amyloliquefaciens subsp. plantarum GR53 heightened induced systemic resistance in infected Chinese cabbage, effectively mitigating R. solani-induced damaging effects and improving plant growth. The results obtained from this study suggest that B. amyloliquefaciens subsp. plantarum GR53 is an effective biocontrol agent to prevent the damage caused by R. solani in Chinese cabbage plants.

In vitro antioxidant activity of Valeriana officinalis against different neurotoxic agents.

PubMed

Sudati, Jéssie Haigert; Fachinetto, Roselei; Pereira, Romaiana Picada; Boligon, Aline Augusti; Athayde, Margareth Linde; Soares, Felix Antunes; de Vargas Barbosa, Nilda Berenice; Rocha, João Batista Teixeira

2009-08-01

Valeriana officinalis L. (Valerian) is widely used as a traditional medicine to improve the quality of sleep. Although V. officinalis have been well documented as promising pharmacological agent; the exact mechanisms by which this plant act is still unknown. Limited literature data have indicated that V. officinalis extracts can exhibit antioxidant properties against iron in hippocampal neurons in vitro. However, there is no data available about the possible antioxidant effect of V. officinalis against other pro-oxidants in brain. In the present study, the protective effect of V. officinalis on lipid peroxidation (LPO) induced by different pro-oxidant agents with neuropathological importance was examined. Ethanolic extract of valerian (0-60 microg/ml) was tested against quinolinic acid (QA); 3-nitropropionic acid; sodium nitroprusside; iron sulfate (FeSO4) and Fe2+/EDTA induced LPO in rat brain homogenates. The effect of V. officinalis in deoxyribose degradation and reactive oxygen species (ROS) production was also investigated. In brain homogenates, V. officinalis inhibited thiobarbituric acid reactive substances induced by all pro-oxidants tested in a concentration dependent manner. Similarly, V. officinalis caused a significant decrease on the LPO in cerebral cortex and in deoxyribose degradation. QA-induced ROS production in cortical slices was also significantly reduced by V. officinalis. Our results suggest that V. officinalis extract was effective in modulating LPO induced by different pro-oxidant agents. These data may imply that V. officinalis extract, functioning as antioxidant agent, can be beneficial for reducing insomnia complications linked to oxidative stress.

Sodium thiosulfate protects brain in rat model of adenine induced vascular calcification.

PubMed

Subhash, N; Sriram, R; Kurian, Gino A

2015-11-01

Vascular bed calcification is a common feature of ends stage renal disease that may lead to a complication in cardiovascular and cerebrovascular beds, which is a promoting cause of myocardial infarction, stroke, dementia and aneurysms. Sodium thiosulfate (STS) due to its multiple properties such as antioxidant and calcium chelation has been reported to prevent vascular calcification in uremic rats, without mentioning its impact on cerebral function. Moreover, the previous studies have not explored the effect of STS on the mitochondrial dysfunction, one of the main pathophysiological features associated with the disease and the main site for STS metabolism. The present study addresses this limitation by using a rat model where 0.75% adenine was administered to induce vascular calcification and 400 mg/kg b wt. of STS was given as preventive and curative agent. The blood and urine chemistries along with histopathology of aorta confirms the renal protective effect of STS in two modes of administration. The brain oxidative stress assessment was made through TBARS level, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, found to be in the near normal level. STS administration not only reduced the mitochondrial oxidative stress (measured by TBARS, SOD, GPx and CAT) but also preserved the mitochondrial respiratory enzyme activities (NADH dehydrogenase, Succinate dehydrogenase and Malate dehydrogenase) and its physiology (measured by P/O ratio and RCR). In fact, the protective effect of STS was prominent, when it was administered as a curative agent, where low H2S and high thiosulfate level was observed along with low cystathionine β synthase activity, confirms thiosulfate mediated renal protection. In conclusion, STS when given after induction of calcification is protective to the brain by preserving its mitochondria, compared to the treatment given concomitantly. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemoprevention of bladder cancer.

PubMed

Kamat, Ashish M; Lamm, Donald L

2002-02-01

The data presented herein, although highly supportive for a protective role of various nutrients against bladder cancer, are far from definitive. Many authorities question the validity of current recommendations for nutritional chemoprevention against bladder cancer. The reason for the wide variations reported in epidemiologic studies lies in the nature of observational studies. Dietary studies are limited in their conclusions because the protection afforded by the consumption of a particular nutrient may be multifactorial, with different components of the food exerting potential chemopreventive effects. Furthermore, measuring levels of nutrients in the food intake of populations is confounded by factors that might affect these levels and also the incidence of cancer. For example, vitamin A can come from animal or vegetarian sources. Because animal fat has been identified as a potential carcinogen in man, depending on the source of the vitamin, varying levels of protection might be deduced. In addition, chemoprevention studies using dietary supplements are expected to have mild effects, and large studies would be required to confirm statistical significance. Even with agents such as intravesical chemotherapy, only half the studies achieve statistical significance [29]. Prospective randomized trials with a large sample size, longer follow-up, and an extended duration of treatment are needed to clarify the association between micronutrients and cancer protection. With these caveats in mind, several recommendations can be made. Simple measures, such as drinking more fluids (especially water), can have a profound impact on the incidence of bladder cancer. Vitamins are being extensively studied in chemopreventive trials for different cancers. There is strong evidence for a chemoprotective effect of vitamin A in bladder cancer. The authors recommend 32,000 IU/day of vitamin A initially, with lower doses (24,000 IU) for persons less than 50 kg. Because liver toxicity is a possibility with long-term administration, the dose should be decreased to 16,000 IU after 3 years. High doses of beta-carotene should be avoided based on a large clinical trial reporting a 25% increase in the number of cases of prostate cancer and a statistically significant increase in the incidence of lung cancer. Vitamin B6 has been studied in several clinical trials in bladder cancer. The US-based Veterans Administration cooperative study found benefit for vitamin B6 when given as a single agent. Data for vitamins C and E are insufficient to recommend either agent as stand-alone treatment. Nonetheless, each of these vitamins is known to have beneficial effects, including improved function of the immune system. It is possible that only a small percentage of patients with bladder cancer respond to vitamins B6, C, or E, yet each is safe, nontoxic, and inexpensive. In an effort to pool the efficacy of individual agents and to increase the power of study, the authors evaluated the combination of vitamins A, B6, C, and E in a double-blind trial. The observed 50% 5-year reduction in tumor recurrence was highly significant and greater than would be expected for any of the individual ingredients and suggests that combinations of nutritional agents may be most appropriate. A large-volume study along similar lines is being conducted. Among the numerous other compounds and dietary substances purported to have chemopreventive effect, soybeans, garlic, and green tea stand out as having the greatest promise and can freely be recommended to patients. For synthetically synthesized agents such as celecoxib, piroxicam, or DFMO, recommendations must be deferred until the results of clinical trials are conclusively in favor of their use. Many of the dietary factors found to be protective against bladder cancer are being investigated in other cancers and are beneficial to general health. Although naturally occurring nutrients are ideal, especially because the delicate balance of various micronutrients might be impossible to synthesize in the laboratory, the general population finds it easier to take vitamin supplements. Unfortunately, dietary changes such as decreasing fat and increasing fruit and vegetable intake are more difficult to initiate. There is a mistaken notion that simply because an agent is naturally occurring, it cannot be as beneficial as taking a substance synthesized in the laboratory. Even in a high-risk group such as nuclear-bomb survivors in Japan, high consumption of vegetables and fruit is protective against bladder cancer [44]. Encouraging patients to follow an essentially healthy food habit lifestyle will be a significant contribution in the fight against cancer.

Protective effects of ψ taraxasterol 3-O-myristate and arnidiol 3-O-myristate isolated from Calendula officinalis on epithelial intestinal barrier.

PubMed

Dall'Acqua, Stefano; Catanzaro, Daniela; Cocetta, Veronica; Igl, Nadine; Ragazzi, Eugenio; Giron, Maria Cecilia; Cecconello, Laura; Montopoli, Monica

2016-03-01

The triterpene esters ᴪ taraxasterol-3-O-myristate (1) and arnidiol-3-O-myristate (2) were tested for their ability to protect epithelial intestinal barrier in an in vitro model. Their effects on ROS production and on trans-epithelial resistance were investigated on CaCo-2 cell monolayers both in basal and stress-induced conditions. Both compounds were able to modulate the stress damage induced by H2O2 and INFγ+TNFα, showing a potential use as model compounds for the study of new therapeutic agents for intestinal inflammations. Copyright © 2016 Elsevier B.V. All rights reserved.

Paraoxonase activity in athletic adolescents.

PubMed

Cakmak, Alpay; Zeyrek, Dost; Atas, Ali; Erel, Ozcan

2010-02-01

Regular physical activity may play a protective role against cardiovascular disease in adults, and paraoxonase activity may serve to mediate this effect. This study compared paraoxonase activity and that of other antioxidative agents in adolescent athletes compared with inactive youth. Paraoxonase level was 177.32 +/- 100.10 (U/L) in children with regular physical activity and 98.11 +/- 40.92 (U/L) in the control group (P < 0.0001). The levels of total antioxidative capacity, total oxidative status, oxidative stress index, and lipid hydroperoxide were significantly higher in the athlete group compared with controls (P < 0.0001). Paraoxonase activity was found to be greater in adolescent athletes, suggesting that regular exercise might provide a cardio-protective effect by this means.

Antioxidant and Cytoprotective Activities of Fucus spiralis Seaweed on a Human Cell in Vitro Model.

PubMed

Pinteus, Susete; Silva, Joana; Alves, Celso; Horta, André; Thomas, Olivier P; Pedrosa, Rui

2017-01-29

Antioxidants play an important role as Reactive Oxygen Species (ROS) chelating agents and, therefore, the screening for potent antioxidants from natural sources as potential protective agents is of great relevance. The main aim of this study was to obtain antioxidant-enriched fractions from the common seaweed Fucus spiralis and evaluate their activity and efficiency in protecting human cells (MCF-7 cells) on an oxidative stress condition induced by H₂O₂. Five fractions, F1-F5, were obtained by reversed-phase vacuum liquid chromatography. F3, F4 and F5 revealed the highest phlorotannin content, also showing the strongest antioxidant effects. The cell death induced by H₂O₂ was reduced by all fractions following the potency order F4 > F2 > F3 > F5 > F1. Only fraction F4 completely inhibited the H₂O₂ effect. To understand the possible mechanisms of action of these fractions, the cellular production of H₂O₂, the mitochondrial membrane potential and the caspase 9 activity were studied. Fractions F3 and F4 presented the highest reduction on H₂O₂ cell production. All fractions decreased both caspase-9 activity and cell membrane depolarization (except F1). Taken all together, the edible F. spiralis reveal that they provide protection against oxidative stress induced by H₂O₂ on the human MCF-7 cellular model, probably acting as upstream blockers of apoptosis.

The use of hormonal contraceptive agents and mood disorders in women.

PubMed

Svendal, Gjertrud; Berk, Michael; Pasco, Julie A; Jacka, Felice N; Lund, Anders; Williams, Lana J

2012-09-01

Mood disorders are a major cause of disability in developed countries, and contraceptive agents among the most widely used medications. The relationship between contraceptive agents and mood is unclear. The aim of this study was therefore to investigate the association between current contraception use and mood disorders in a random population-based sample of women. This study examined epidemiological data obtained from 498 women aged 20-50year participating in the Geelong Osteoporosis Study (GOS). Mood disorders were diagnosed using a clinical interview (SCID-I/NP) and information on medication use and other lifestyle factors were documented. After adjusting for age and socioeconomic status (SES), women taking progestin-only contraceptive agents had an increased likelihood of a current mood disorder (OR 3.0 95%CI: 1.1-7.8, p=0.03). In contrast, women taking combined contraceptive agents had a decreased likelihood of a current mood disorder, adjusting this for age and SES (OR 0.3 95%CI: 0.1, 0.9 p=0.03). These findings were not explained by weight, physical activity level, past depression, number of medical conditions or cigarette smoking. This study is cross-sectional, which precludes any determination regarding the direction of the relationships. These data suggest a protective effect of the combined contraceptive pill, and a deleterious effect of progestin only agents in regards to mood disorders. Copyright © 2012 Elsevier B.V. All rights reserved.

Cell-wall preparation containing poly-γ-D-glutamate covalently linked to peptidoglycan, a straightforward extractable molecule, protects mice against experimental anthrax infection.

PubMed

Candela, Thomas; Dumetz, Fabien; Tosi-Couture, Evelyne; Mock, Michèle; Goossens, Pierre L; Fouet, Agnès

2012-12-17

Bacillus anthracis is the causative agent of anthrax that is characterized by septicemia and toxemia. Many vaccine strategies were described to counteract anthrax infection. In contrast with veterinary live vaccines, currently human vaccines are acellular with the protective antigen, a toxin component, as the main constituent. However, in animal models this vaccine is less efficient than the live vaccine. In this study, we analyzed the protection afforded by a single extractable surface element. The poly-γ-D-glutamate capsule is covalently linked to the peptidoglycan. A preparation of peptidoglycan-linked poly-γ-D-glutamate (GluPG) was tested for its immunogenicity and its protective effect. GluPG injection, in mice, elicited the production of specific antibodies directed against poly-glutamate and partially protected the animals against lethal challenges with a non-toxinogenic strain. When combined to protective antigen, GluPG immunization conferred full protection against cutaneous anthrax induced with a fully virulent strain. Copyright © 2012 Elsevier Ltd. All rights reserved.

40 CFR Appendix O to Subpart G of... - Substitutes Listed in the September 27, 2006 Final Rule, Effective November 27, 2006

Code of Federal Regulations, 2012 CFR

2012-07-01

... latest edition of the NFPA 2001 Standard for Clean Agent Fire Extinguishing Systems, for whichever... Systems.Sodium bicarbonate release in all settings should be targeted so that increased blood pH level... to be in environments protected by Envirogel with sodium bicarbonate additive extinguishing systems...

40 CFR Appendix O to Subpart G of... - Substitutes Listed in the September 27, 2006 Final Rule, Effective November 27, 2006

Code of Federal Regulations, 2013 CFR

2013-07-01

... latest edition of the NFPA 2001 Standard for Clean Agent Fire Extinguishing Systems, for whichever... Systems.Sodium bicarbonate release in all settings should be targeted so that increased blood pH level... to be in environments protected by Envirogel with sodium bicarbonate additive extinguishing systems...

40 CFR Appendix O to Subpart G of... - Substitutes Listed in the September 27, 2006 Final Rule, Effective November 27, 2006

Code of Federal Regulations, 2011 CFR

2011-07-01

... latest edition of the NFPA 2001 Standard for Clean Agent Fire Extinguishing Systems, for whichever... Systems.Sodium bicarbonate release in all settings should be targeted so that increased blood pH level... to be in environments protected by Envirogel with sodium bicarbonate additive extinguishing systems...

40 CFR Appendix O to Subpart G of... - Substitutes Listed in the September 27, 2006 Final Rule, Effective November 27, 2006

Code of Federal Regulations, 2014 CFR

2014-07-01

... latest edition of the NFPA 2001 Standard for Clean Agent Fire Extinguishing Systems, for whichever... Systems.Sodium bicarbonate release in all settings should be targeted so that increased blood pH level... to be in environments protected by Envirogel with sodium bicarbonate additive extinguishing systems...

A Review of the Integration of Classical Biological Control with other Management Techniques to Manage Invasive Weeds in Natural Areas and Rangelands

USDA-ARS?s Scientific Manuscript database

Integrating classical biological control with other management techniques such as herbicide, fire, mechanical control, grazing, or plant competition, can be the most effective way to manage invasive weeds in natural areas and rangelands. Biological control agents can be protected from potential nega...

Impact of Environmental Education on the Knowledge and Attitude of Students towards the Environment

ERIC Educational Resources Information Center

Erhabor, Norris I.; Don, Juliet U.

2016-01-01

Environmentally aware and empowered youths are potentially the greatest agent of change for the long term protection and stewardship of the environment. Thus environmental education which promotes such change will enable these youths to have a greater voice on environmental issue if effectively implemented in Nigeria. Hence, this study was…

[The bacterial biofilm and the possibilities of chemical plaque control. Literature review].

PubMed

Gera, István

2008-06-01

Most microorganisms in the oral cavity attach to surfaces and form matrix-embedded biofilms. Biofilms are structured and spatially organized, composed of consortia of interacting microorganisms. The properties of the mass of biofilm are different from that of the simple sum of the component species. The older the plaque (biofilm) is the more structurally organized and become more resistant to environmental attacks. The bacterial community favors the growth of obligatory anaerobic microorganisms. The most effective means of the elimination of matured biofilm is the mechanical disruption of the interbacterial protective matrix and removal of bacterial colonies. The antiseptic agents are primarily effective in the prevention of biofilm formation and anticipation of the maturation of the bacterial plaque. Bacteria in matured biofilms are less susceptible to antimicrobial agents because several physical and biological factors protect the bacterial consortia. To kill bacteria in a matured, well organized biofilm, significantly higher concentration and longer exposition are required. Antiseptic mouthrinses in a conventional dose and time can only reach the superficial bacteria while the bacteria in the depth of the biofilm remains intact. Therefore, the efficacy of any antiseptic mouthwash depends not just on its microbicidal properties demonstrated in vitro, but also on its ability to penetrate the organized biofilm on the teeth. Recent studies have demonstrated that both bisbiguanid compounds and essential oils are capable of penetrating the biofilm, and reduce established plaque and gingivitis. The essential oils showed high penetrability and were more effective on organized biofilm than stannous fluorides or triclosan copolymer antiplaque agents.

Insect-resistant food packaging film development using cinnamon oil and microencapsulation technologies.

PubMed

Kim, In-Hah; Han, Jaejoon; Na, Ja Hyun; Chang, Pahn-Sik; Chung, Myung Sub; Park, Ki Hwan; Min, Sea C

2013-02-01

Insect-resistant films containing a microencapsulated insect-repelling agent were developed to protect food products from the Indian meal moth (Plodia interpunctella). Cinnamon oil (CO), an insect repelling agent, was encapsulated with gum arabic, whey protein isolate (WPI)/maltodextrin (MD), or poly(vinyl alcohol) (PVA). A low-density polyethylene (LDPE) film was coated with an ink or a polypropylene (PP) solution that incorporated the microcapsules. The encapsulation efficiency values obtained with gum arabic, WPI/MD, and PVA were 90.4%, 94.6%, and 80.7%, respectively. The films containing a microcapsule emulsion of PVA and CO or incorporating a microcapsule powder of WPI/MD and CO were the most effective (P < 0.05) at repelling moth larvae. The release rate of cinnamaldehyde, an active repellent of cinnamaldehyde, in the PP was 23 times lower when cinnamaldehyde was microencapsulated. Coating with the microcapsules did not alter the tensile properties of the films. The invasion of larvae into cookies was prevented by the insect-repellent films, demonstrating potential for the films in insect-resistant packaging for food products. The insect-repelling effect of cinnamon oil incorporated into LDPE films was more effective with microencapsulation. The system developed in this research with LDPE film may also be extended to other food-packaging films where the same coating platform can be used. This platform is interchangeable and easy to use for the delivery of insect-repelling agents. The films can protect a wide variety of food products from invasion by the Indian meal moth. © 2013 Institute of Food Technologists®

Radioprotection of mouse skin vasculature and the RIF-1 fibrosarcoma by WR-2721

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penhaligon, M.

1984-09-01

The degree of radioprotection obtained with WR-2721 is critically dependent upon the oxygen tension of the tissue concerned. It was therefore considered of interest to examine the response of vascular tissue, which would be supposedly well oxygenated, to treatment with WR-2721 plus X rays. The response of this tissue is of interest because of its role in late radiation damage. In addition, for therapeutic gain an agent must protect normal tissue without concomitant tumor protection. However, data on tumor radioprotection have been conflicting and therefore the effect of WR-2721 on an experimental tumor was also tested. Vascular damage was assessedmore » using the fact that tumors grow more slowly in irradiated beds (Tumor Bed Effect). WR-2721 injected 30 minutes before 5 to 30 Gy X rays protected skin stroma by a factor of 1.6. However, WR-2721 given 10 to 60 minutes before 20 Gy X rays to the RIF-1 tumor had either no effect or was protective, according to the method of immobilizing the mice during irradiation.« less

Licorice Pretreatment Protects Against Brain Damage Induced by Middle Cerebral Artery Occlusion in Mice.

PubMed

Lim, Chiyeon; Lim, Sehyun; Lee, Byoungho; Kim, Buyeo; Cho, Suin

2018-05-01

Licorice is extracted from the roots of plants in the Glycyrrhiza genus, especially Glycyrrhiza uralensis in China and Korea. It has several pharmacological activities, including neuro-protective, anti-fungal, and anti-cariogenic effects. Ischemia/reperfusion-induced brain injury is a leading cause of adult disability and death; thus, the identification of anti-apoptotic, neuro-protective therapeutic agents is viewed as an attractive drug development strategy. Infarct volumes and the expression of several apoptosis-related proteins, including Bcl-xL, Bcl-2, caspase-8, and caspase-9, were evaluated by western blotting in the brains of mice subjected to middle cerebral artery occlusion (MCAO). Three consecutive days of oral pretreatment with the methanol extract of licorice (GRex) significantly reduced infarct volumes 24 h after MCAO. In addition, GRex effectively inhibited the activation of caspase-9 by upregulating protein expression of Bcl-xL and Bcl-2. The neuro-protective effect of licorice was due to its regulation of apoptosis-related proteins. These data suggest that licorice could be a potential candidate for the treatment of ischemia-induced brain damage.

The effect of resveratrol on protecting corneal epithelial cells from cytotoxicity caused by moxifloxacin and benzalkonium chloride.

PubMed

Tsai, Tzu-Yun; Chen, Ta-Ching; Wang, I-Jong; Yeh, Chao-Yuan; Su, Ming-Jai; Chen, Ruey-Hua; Tsai, Tzu-Hsun; Hu, Fung-Rong

2015-02-10

Moxifloxacin (MOX), a fourth generation fluoroquinolone (FQ), has a wide antibacterial spectrum, but may show cytotoxicity characterized by high productions of reactive oxygen species (ROS). This study investigated the protective role of a common antioxidant agent, resveratrol (trans-3,5,4'-trihydroxystilbene), against the cytotoxicity caused by MOX. Experiments were performed with a human corneal epithelial cell line (HCECs; ATCC-CRL-11515). Another commonly used FQ, levofloxacin (LEV), and the most commonly used preservatives, benzalkonium chloride (BAC), were also used for comparison with MOX. Cell viability and morphologic changes after treatment were evaluated with trypan blue exclusion assay, propidium iodine/annexin V-FITC staining, and flow cytometry. Chemiluminescence immunoassay was used for ROS quantification. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, wound healing assay, and intracellular detections of oxidative stress were performed to evaluate the effects of resveratrol. The MOX group, similar to the BAC group, showed significant cell shrinkage and death compared with the LEV group. High ROS production in HCECs of MOX group was observed both by chemiluminescence immunoassay and intracellular images. Within the observations of MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay, live cell images, and wound healing process in vitro, the cytotoxic effects of the MOX and BAC groups were opposed by resveratrol. Human corneal epithelial cells pretreated with resveratrol demonstrated better cell viability and healing rate in the early stage. The protective effects of antioxidant agents indicate that MOX, similar to BAC, causes oxidative stress-related cell damage. The results also inspired us to think about a "supplementary regimen" to increase safety and decrease the adverse effect in the treatment of corneal infections. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Chimeric vaccine composed of viral peptide and mammalian heat-shock protein 60 peptide protects against West Nile virus challenge

PubMed Central

Gershoni-Yahalom, Orly; Landes, Shimon; Kleiman-Shoval, Smadar; Ben-Nathan, David; Kam, Michal; Lachmi, Bat-El; Khinich, Yevgeny; Simanov, Michael; Samina, Itzhak; Eitan, Anat; Cohen, Irun R; Rager-Zisman, Bracha; Porgador, Angel

2010-01-01

The protective efficacy and immunogenicity of a chimeric peptide against West Nile virus (WNV) was evaluated. This virus is the aetiological agent of West Nile fever, which has recently emerged in the western hemisphere. The rapid spread of WNV throughout North America, as well as the constantly changing epidemiology and transmission of the virus by blood transfusion and transplantation, have raised major public-health concerns. Currently, there are no effective treatments for WNV or vaccine for human use. We previously identified a novel, continuous B-cell epitope from domain III of the WNV envelope protein, termed Ep15. To test whether this epitope can protect against WNV infection, we synthesized a linear chimeric peptide composed of Ep15 and the heat-shock protein 60 peptide, p458. The p458 peptide is an effective carrier peptide for subunit vaccines against other infectious agents. We now report that mice immunized with the chimeric peptide, p458-Ep15, were resistant to lethal challenges with three different WNV strains. Moreover, their brains were free of viral genome and infectious virus. Mice immunized with Ep15 alone or with p431-Ep15, a control conjugate, were not protected. The chimeric p458-Ep15 peptide induced WNV-specific immunoglobulin G antibodies that neutralized the virus and induced the secretion of interferon-γin vitro. Challenge of chimeric peptide-immunized mice considerably enhanced WNV-specific neutralizing antibodies. We conclude that this chimeric peptide can be used for formulation of a human vaccine against WNV. PMID:20331473

Chimeric vaccine composed of viral peptide and mammalian heat-shock protein 60 peptide protects against West Nile virus challenge.

PubMed

Gershoni-Yahalom, Orly; Landes, Shimon; Kleiman-Shoval, Smadar; Ben-Nathan, David; Kam, Michal; Lachmi, Bat-El; Khinich, Yevgeny; Simanov, Michael; Samina, Itzhak; Eitan, Anat; Cohen, Irun R; Rager-Zisman, Bracha; Porgador, Angel

2010-08-01

The protective efficacy and immunogenicity of a chimeric peptide against West Nile virus (WNV) was evaluated. This virus is the aetiological agent of West Nile fever, which has recently emerged in the western hemisphere. The rapid spread of WNV throughout North America, as well as the constantly changing epidemiology and transmission of the virus by blood transfusion and transplantation, have raised major public-health concerns. Currently, there are no effective treatments for WNV or vaccine for human use. We previously identified a novel, continuous B-cell epitope from domain III of the WNV envelope protein, termed Ep15. To test whether this epitope can protect against WNV infection, we synthesized a linear chimeric peptide composed of Ep15 and the heat-shock protein 60 peptide, p458. The p458 peptide is an effective carrier peptide for subunit vaccines against other infectious agents. We now report that mice immunized with the chimeric peptide, p458-Ep15, were resistant to lethal challenges with three different WNV strains. Moreover, their brains were free of viral genome and infectious virus. Mice immunized with Ep15 alone or with p431-Ep15, a control conjugate, were not protected. The chimeric p458-Ep15 peptide induced WNV-specific immunoglobulin G antibodies that neutralized the virus and induced the secretion of interferon-gammain vitro. Challenge of chimeric peptide-immunized mice considerably enhanced WNV-specific neutralizing antibodies. We conclude that this chimeric peptide can be used for formulation of a human vaccine against WNV.

46 CFR 95.16-60 - System piping installation testing.

Code of Federal Regulations, 2012 CFR

2012-10-01

... VESSELS FIRE PROTECTION EQUIPMENT Fixed Clean Agent Gas Extinguishing Systems, Details § 95.16-60 System piping installation testing. (a) Halocarbon systems. A pressure test using the extinguishing agent, air... installation and before extinguishing agent cylinders are connected. (1) Except as otherwise specified in this...

46 CFR 95.16-60 - System piping installation testing.

Code of Federal Regulations, 2013 CFR

2013-10-01

... VESSELS FIRE PROTECTION EQUIPMENT Fixed Clean Agent Gas Extinguishing Systems, Details § 95.16-60 System piping installation testing. (a) Halocarbon systems. A pressure test using the extinguishing agent, air... installation and before extinguishing agent cylinders are connected. (1) Except as otherwise specified in this...

46 CFR 95.16-60 - System piping installation testing.

Code of Federal Regulations, 2014 CFR

2014-10-01

... VESSELS FIRE PROTECTION EQUIPMENT Fixed Clean Agent Gas Extinguishing Systems, Details § 95.16-60 System piping installation testing. (a) Halocarbon systems. A pressure test using the extinguishing agent, air... installation and before extinguishing agent cylinders are connected. (1) Except as otherwise specified in this...

30 CFR 56.6000 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by... by a liquid to form a flammable vapor-air mixture near the surface of the liquid. Igniter cord. A... initiate other explosives or blasting agents. Safety switch. A switch that provides shunt protection in...

30 CFR 56.6000 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by... by a liquid to form a flammable vapor-air mixture near the surface of the liquid. Igniter cord. A... initiate other explosives or blasting agents. Safety switch. A switch that provides shunt protection in...

30 CFR 56.6000 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... following definitions apply in this subpart. Blasting agent. Any substance classified as a blasting agent by... by a liquid to form a flammable vapor-air mixture near the surface of the liquid. Igniter cord. A... initiate other explosives or blasting agents. Safety switch. A switch that provides shunt protection in...

Pentadecapeptide BPC 157, cimetidine, ranitidine, bromocriptine, and atropine effect in cysteamine lesions in totally gastrectromized rats: a model for cytoprotective studies.

PubMed

Sikirić, P; Mikus, D; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Perić, J; Konjevoda, P; Perović, D; Jurina, L; Hanzevacki, M; Separović, J; Gjurasin, M; Jadrijević, S; Jelovac, N; Miklić, P; Buljat, G; Marović, A

1997-05-01

A superior effectiveness in various lesion assays was noted for the novel pentadecapeptide BPC 157, originated from human gastric juice protein (BPC) and claimed to be a cytoprotective agent. From this viewpoint, as a previously untreated experimental improvement to create an acid-free environmental for cytoprotection studies, total gastrectomy was done 24 hr before the ulcerogenic procedure. In the absence of stomach and gastric acid, the damaging effects of cysteamine (400 mg/kg subcutaneously, death 24 hr thereafter), to date thought to be an acid-related duodenal ulcerogen, and the BPC 157 cytoprotective effect (10 microg or 10 ng/kg intraperitoneally) were further challenged. BPC 157 was compared with reference agents [cimetidine (50), ranitidine (10), omeprazole (10), bromocriptine (10) and atropine (10) (mg/kg intraperitoneally, 1 hr before cysteamine] known to be also cytoprotective. In naive rats, with intact stomach, all of them showed a strong beneficial effect. Interestingly, in gastrectomized animals, the application of BPC 157 or the reference agents before cysteamine significantly prevented the otherwise severe duodenal lesion development noted in the control gastrectomized cysteamine rats. In groups without cysteamine, no lesions were noted (laparotomy, gastrectomy only, 24 or 48 hr postsurgical period), nor was lesion potentiation seen in cysteamine-treated laparotomized animals. In summary, these findings--equal damaging effect of cysteamine and equal protection of pentadecapeptide BPC 157 and reference agents in gastrectomized and rats with intact stomach--seem to be particularly relevant for a cytoprotective viewpoint. Without a stomach, the cysteamine damaging effect was convincingly defined as an essential gastric acid-independent injury (analogous to ethanol gastric lesions). Likewise, a high "cytoprotective capacity," apparently acid independent, common for all tested agents (novel pentadecapeptide BPC 157, cimetidine, ranitidine, omeprazole and atropine) could be clearly stressed.

Skin protection against UV light by dietary antioxidants.

PubMed

Fernández-García, Elisabet

2014-09-01

There is considerable interest in the concept of additional endogenous photoprotection by dietary antioxidants. A number of efficient micronutrients are capable of contributing to the prevention of UV damage in humans. These compounds protect molecular targets by scavenging reactive oxygen species, including excited singlet oxygen and triplet state molecules, and also modulate stress-dependent signaling and/or suppress cellular and tissue responses like inflammation. Micronutrients present in the diet such as carotenoids, vitamins E and C, and polyphenols contribute to antioxidant defense and may also contribute to endogenous photoprotection. This review summarizes the literature concerning the use of dietary antioxidants as systemic photoprotective agents towards skin damage induced by UVA and UVB. Intervention studies in humans with carotenoid-rich diets have shown photoprotection. Interestingly, rather long treatment periods (a minimum of 10 weeks) were required to achieve this effect. Likewise, dietary carotenoids exert their protective antioxidant function in several in vitro and in vivo studies when present at sufficiently high concentration. A combination of vitamins E and C protects the skin against UV damage. It is suggested that daily consumption of dietary polyphenols may provide efficient protection against the harmful effects of solar UV radiation in humans. Furthermore, the use of these micronutrients in combination may provide an effective strategy for protecting human skin from damage by UV exposure.

Antibody profiling using a recombinant protein-based multiplex ELISA array accelerates recombinant vaccine development: Case study on red sea bream iridovirus as a reverse vaccinology model.

PubMed

Matsuyama, Tomomasa; Sano, Natsumi; Takano, Tomokazu; Sakai, Takamitsu; Yasuike, Motoshige; Fujiwara, Atushi; Kawato, Yasuhiko; Kurita, Jun; Yoshida, Kazunori; Shimada, Yukinori; Nakayasu, Chihaya

2018-05-03

Predicting antigens that would be protective is crucial for the development of recombinant vaccine using genome based vaccine development, also known as reverse vaccinology. High-throughput antigen screening is effective for identifying vaccine target genes, particularly for pathogens for which minimal antigenicity data exist. Using red sea bream iridovirus (RSIV) as a research model, we developed enzyme-linked immune sorbent assay (ELISA) based RSIV-derived 72 recombinant antigen array to profile antiviral antibody responses in convalescent Japanese amberjack (Seriola quinqueradiata). Two and three genes for which the products were unrecognized and recognized, respectively, by antibodies in convalescent serum were selected for recombinant vaccine preparation, and the protective effect was examined in infection tests using Japanese amberjack and greater amberjack (S. dumerili). No protection was provided by vaccines prepared from gene products unrecognized by convalescent serum antibodies. By contrast, two vaccines prepared from gene products recognized by serum antibodies induced protective immunity in both fish species. These results indicate that ELISA array screening is effective for identifying antigens that induce protective immune responses. As this method does not require culturing of pathogens, it is also suitable for identifying protective antigens to un-culturable etiologic agents. Copyright © 2018 Elsevier Ltd. All rights reserved.

Surface and protective properties of dispersions of film-formers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turishcheva, R.A.; Bakaleinikov, M.B.; Minkina, E.N.

1983-03-01

This article reports on studies of the surface and protective properties of 20% dispersions of film-formers most typically used in film-forming inhibited petroleum-base compositions (FIPC): solid hydrocarbons, fatty acid soaps, asphalt, polymers, natural resins, modified vegetable oils, and an inorganic thickening agent. Investigates the dispersions of Butosil and lithium stearate at respective concentrations of 10% and 8%, in view of the high thickening power of these film-formers. Classifies all of the studied FIPC film-forming components into 2 groups: those wth little thickening effect, a low level of adhesion-cohesion interaction, and a high level of surface and protective properties (the oxidizedmore » solid hydrocarbons and the polymers); and the film-formers that have a large thickening effect, a high level of adhesion-cohesion interaction, and a low level of surface and protective properties (the fatty acid soaps, the solid hydrocarbons, and Butosil). Recommends combining film-formers of both groups in developing new grades of FIPCs.« less

Advances in the Preclinical Study of Some Flavonoids as Potential Antidepressant Agents

PubMed Central

German-Ponciano, León Jesús; Rosas-Sánchez, Gilberto Uriel; Rivadeneyra-Domínguez, Eduardo

2018-01-01

Flavonoids are phenolic compounds found commonly in plants that protect them against the negative effects of environmental insults. These secondary metabolites have been widely studied in preclinical research because of their biological effects, particularly as antioxidant agents. Diverse flavonoids have been studied to explore their potential therapeutic effects in the treatment of disorders of the central nervous system, including anxiety and depression. The present review discusses advances in the study of some flavonoids as potential antidepressant agents. We describe their behavioral, physiological, and neurochemical effects and the apparent mechanism of action of their preclinical antidepressant-like effects. Natural flavonoids produce antidepressant-like effects in validated behavioral models of depression. The mechanism of action of these effects includes the activation of serotonergic, dopaminergic, noradrenergic, and γ-aminobutyric acid-ergic neurotransmitter systems and an increase in the production of neural factors, including brain-derived neurotrophic factor and nerve growth factor. Additionally, alterations in the function of tropomyosin receptor kinase B and activity of the enzyme monoamine oxidase A have been reported. In conclusion, preclinical research supports the potential antidepressant effects of some natural flavonoids, which opens new possibilities of evaluating these substances to develop complementary therapeutic alternatives that could ameliorate symptoms of depressive disorders in humans. PMID:29623232

Effects of Egg Shell Membrane Hydrolysates on Anti-Inflammatory, Anti-Wrinkle, Anti-Microbial Activity and Moisture-Protection.

PubMed

Yoo, Jinhee; Park, Kimoon; Yoo, Youngji; Kim, Jongkeun; Yang, Heejin; Shin, Youngjae

2014-01-01

This study was conducted to examine the effects of eggshell membrane hydrolysates (ESMH) on the anti-inflammatory, anti-wrinkle, anti-microbial activity, and moisture-protection for cosmetic use. Whole ESMH (before fractionation), and fraction I (>10 kDa), fraction II (3-10 kDa), and fraction III (<3 kDa) of the hydrolysates were assessed in this experiment. As lipopolysaccharide (LPS) and IFN-γ caused the inflammation on Raw264.7 cell, whole ESMH and fraction I showed to be effective in inhibiting the induction of cell inflammation depending on the concentration, and also showed outstanding effect to suppress the skin inflammation. Fraction I inhibited collagenase and elastase activities to a greater extent than the other fractions, while all fractions had antibiotic effects at concentrations of 10 mg/disc and 20 mg/disc. In addition, it showed the moisture protection effects of skin on the holding amount and losing amount of moisture in upper-inner arm of the human body with a relatively low loss rate in skin, which confirmed that the hydrolyzed fractions of ESM helps to form the superior protective layer of moisture. It was concluded that ESMH fractions with different molecular weights, especially the 10 kDa fraction, have anti-lipopolysaccharide, anti-IFN-γ-induced inflammation, anti- collagenase and elastase activities, and thus can be used as a cosmetic agent to protect skin.

A crucial role for plasmacytoid dendritic cells in antiviral protection by CpG ODN–based vaginal microbicide

PubMed Central

Shen, Hong; Iwasaki, Akiko

2006-01-01

Topical microbicides represent a promising new approach to preventing HIV and other sexually transmitted infections. TLR agonists are ideal candidates for microbicides, as they trigger a multitude of antiviral genes effective against a broad range of viruses. Although vaginal application of CpG oligodeoxynucleotides (ODNs) and poly I:C has been shown to protect mice from genital herpes infection, the mechanism by which these agents provide protection remains unclear. Here, we show that plasmacytoid DCs (pDCs) are required for CpG ODN–mediated protection against lethal vaginal challenge with herpes simplex virus type 2 (HSV-2). Moreover, we demonstrate that cells of both the hematopoietic and stromal compartments must respond to CpG ODN via TLR9 and to type I IFNs through IFN-αβ receptor (IFN-αβR) for protection. Thus, crosstalk between pDCs and vaginal stromal cells provides for optimal microbicide efficacy. Our results imply that temporally and spatially controlled targeting of CpG ODN to pDCs and epithelial cells can potentially maximize their effectiveness as microbicides while minimizing the associated inflammatory responses. PMID:16878177

Protective single/combined treatment with betel leaf and turmeric against methyl (acetoxymethyl) nitrosamine-induced hamster oral carcinogenesis.

PubMed

Azuine, M A; Bhide, S V

1992-05-28

The inhibitory effect of oral administration of betel-leaf extract (BLE) and 2 of its constituents, beta-carotene and alpha-tocopherol, as single agents or in combination with dietary turmeric on methyl(acetoxymethyl)nitrosamine (DMN-OAC)-induced oral carcinogenesis in Syrian hamsters was studied. DMN-OAC was administered twice monthly for 6 months. The chemopreventive effect of BLE or its constituents with turmeric was determined by comparing tumor incidence observed in treated groups with that seen in control animals. The apparent site-specific chemopreventive effect of BLE or its constituents was demonstrated by inhibition of tumor incidence, reduction of tumor burden, extension of the tumor latency period and regression of established, frank tumors. The inhibitory effect of BLE or its constituents combined with turmeric was higher than that of the individual constituents. The study suggests that BLE could be developed as a potential chemopreventive agent for human oral cancer.

Pyrrole as a promising electrolyte additive to trap polysulfides for lithium-sulfur batteries

NASA Astrophysics Data System (ADS)

Yang, Wu; Yang, Wang; Song, Ailing; Gao, Lijun; Sun, Gang; Shao, Guangjie

2017-04-01

Lithium-sulfur batteries are a promising energy storage devices beyond conventional lithium ion batteries. However, the "shuttle effect" of soluble polysulfides is a major barrier between electrodes, resulting in rapid capacity fading. To address above issue, pyrrole has been investigated as an electrolyte additive to trap polysulfides. When pyrrole is added into electrolyte, a surface protective layer of polypyrrole can be formed on the sulfur cathode, which not only acts as a conductive agent to provide an effective electron conduction path but also acts as an absorbing agent and barrier layer suppressing the diffusion of polysulfide intermediates. The results demonstrate that an appropriate amount of pyrrole added into the electrolyte leads to excellent cycling stability and rate capability. Apparently, pyrrole is an effective additive for the entrapment of polysulfides of lithium-sulfur batteries.

Engineering Ultimate Self-Protection in Autonomic Agents for Space Exploration Missions

NASA Technical Reports Server (NTRS)

Sterritt, Roy; Hinchey, Mike

2005-01-01

NASA's Exploration Initiative (EI) will push space exploration missions to the limit. Future missions will be required to be self-managing as well as self-directed, in order to meet the challenges of human and robotic space exploration. We discuss security and self protection in autonomic agent based-systems, and propose the ultimate self-protection mechanism for such systems-self-destruction. Like other metaphors in Autonomic Computing, this is inspired by biological systems, and is the analog of biological apoptosis. Finally, we discus the role it might play in future NASA space exploration missions.

Pre-Treatment with Amifostine Protects against Cyclophosphamide-Induced Disruption of Taste in Mice

PubMed Central

Mukherjee, Nabanita; Carroll, Brittany L.; Spees, Jeffrey L.; Delay, Eugene R.

2013-01-01

Cyclophosphamide (CYP), a commonly prescribed chemotherapy drug, has multiple adverse side effects including alteration of taste. The effects on taste are a cause of concern for patients as changes in taste are often associated with loss of appetite, malnutrition, poor recovery and reduced quality of life. Amifostine is a cytoprotective agent that was previously shown to be effective in preventing chemotherapy-induced mucositis and nephrotoxicity. Here we determined its ability to protect against chemotherapy-induced damage to taste buds using a mouse model of CYP injury. We conducted detection threshold tests to measure changes in sucrose taste sensitivity and found that administration of amifostine 30 mins prior to CYP injection protected against CYP-induced loss in taste sensitivity. Morphological studies showed that pre-treatment with amifostine prevented CYP-induced reduction in the number of fungiform taste papillae and increased the number of taste buds. Immunohistochemical assays for markers of the cell cycle showed that amifostine administration prevented CYP-induced inhibition of cell proliferation and also protected against loss of mature taste cells after CYP exposure. Our results indicate that treatment of cancer patients with amifostine prior to chemotherapy may improve their sensitivity for taste stimuli and protect the taste system from the detrimental effects of chemotherapy. PMID:23626702

Efficacy studies of Reactive Skin Decontamination Lotion, M291 Skin Decontamination Kit, 0.5% bleach, 1% soapy water, and Skin Exposure Reduction Paste Against Chemical Warfare Agents, part 2: guinea pigs challenged with soman.

PubMed

Braue, Ernest H; Smith, Kelly H; Doxzon, Bryce F; Lumpkin, Horace L; Clarkson, Edward D

2011-03-01

This report, the second in a series of five, directly compares the efficacy of Reactive Skin Decontamination Lotion (RSDL), the M291 Skin Decontamination Kit (SDK), 0.5% bleach (sodium or calcium hypochlorite solution), 1% soapy water, and Skin Exposure Reduction Paste Against Chemical Warfare Agents (SERPACWA) in the haired guinea pig model following exposure to soman (GD). In all experiments, guinea pigs were close-clipped and given anesthesia. In the decontamination experiments, the animals were challenged with GD and decontaminated after a 2-minute delay for the standard procedure or at longer times for the delayed-decontamination experiments. Positive control animals were challenged with GD in the same manner as the treated animals, except that they received no treatment. All animals were observed during the first 4 hours and again at 24 hours after exposure for signs of toxicity and death. The protective ratio (PR, defined as the median lethal dose [LD(50)] of the treatment group divided by the LD(50) of the untreated positive control animals) was calculated from the derived probit dose-response curves established for each treatment group and nontreated control animals. SERPACWA was applied as a thin coating (0.1 mm thick), allowed to dry for 15 minutes, and challenged with GD. After a 2-hour challenge, any remaining GD was blotted off the animal, but no additional decontamination was done. Significance in this report is defined as p <.05. Neat (undiluted) GD was used to challenge all animals in these studies. In the standard 2-minute GD decontamination experiments, the calculated PRs for RSDL, 0.5% bleach, 1% soapy water, and M291 SDK were 14, 2.7, 2.2, and 2.6, respectively. RSDL was by far the most effective decontamination product tested and significantly better than any of the other products. Bleach, soapy water, and the M291 SDK provided equivalent and modest protection. Since only RSDL provided at least good protection (PR > 5), it was the only decontamination product evaluated for delayed decontamination. In the GD delayed-decontamination experiments, the calculated LT(50) (the delayed-decontamination time at which 50% of the animals die in the test population following a 5-LD(50) challenge) value for RSDL was only 4.0 minutes. Several conclusions can be drawn from this study: 1) Reactive Skin Decontamination Lotion provided superior protection against GD compared with the other products tested; 2) The 0.5% bleach solution, the 1% soapy water solution, and the M291 SDK were less effective than RSDL, but still provided modest (2 < PR < 5) protection against GD; 3) Reactive Skin Decontamination Lotion, the best product tested, did not provide significant protection against GD when decontamination was delayed for more than 3 minutes; 4) Skin Exposure Reduction Paste Against Chemical Warfare Agents provided significant, but modest, protection against GD; 5) There was good correlation between using the rabbit model and the guinea pig model for decontamination efficacy evaluations; and 6) Soman (GD) is an agent of real concern because it is very difficult to decontaminate and the effects of exposure are difficult to treat.

Melatonin protects against taurolithocholic-induced oxidative stress in rat liver.

PubMed

Fuentes-Broto, Lorena; Miana-Mena, Francisco J; Piedrafita, Eduardo; Berzosa, César; Martínez-Ballarín, Enrique; García-Gil, Francisco A; Reiter, Russel J; García, Joaquín J

2010-08-01

Cholestasis, encountered in a variety of clinical disorders, is characterized by intracellular accumulation of toxic bile acids in the liver. Furthermore, oxidative stress plays an important role in the pathogenesis of bile acids. Taurolithocholic acid (TLC) was revealed in previous studies as the most pro-oxidative bile acid. Melatonin, a well-known antioxidant, is a safe and widely used therapeutic agent. Herein, we investigated the hepatoprotective role of melatonin on lipid and protein oxidation induced by TLC alone and in combination with FeCl(3) and ascorbic acid in rat liver homogenates and hepatic membranes. The lipid peroxidation products, malondialdehyde and 4-hydroxyalkenals (MDA + 4-HDA), and carbonyl levels were quantified as indices of oxidative damage to hepatic lipids and proteins, respectively. In the current study, the rise in MDA + 4-HDA levels induced by TLC was inhibited by melatonin in a concentration-dependent manner in both liver homogenates and in hepatic membranes. Melatonin also had protective effects against structural damage to proteins induced by TLC in membranes. These results suggest that the indoleamine melatonin may potentially act as a protective agent in the therapy of those diseases that involve bile acid toxicity. Published 2010 Wiley-Liss, Inc.

Gastroprotective effects of honey and glucose-fructose-sucrose-maltose mixture against ethanol-, indomethacin-, and acidified aspirin-induced lesions in the rat.

PubMed

Gharzouli, Kamel; Amira, Smain; Gharzouli, Akila; Khennouf, Seddik

2002-11-01

The gastric cytoprotective properties of natural honey (monofloral and polyfloral specimens) and of a glucose-fructose-sucrose-maltose mixture (GFSM) was evaluated in the rat using absolute ethanol, indomethacin and acidified acetylsalicylic acid (ASA-HCl) as necrotising agents. Prior gastric administration of honey (2.5 g/kg) to animals induced a net reduction of hemorrhagic lesions length of the mucosa. Protection of the stomach elicited by both types of honey and GFSM was almost total against ethanol-induced lesions. Similar results were also observed when using ASA-HCl except that the percent protection was 87%. The percent reduction of indomethacin-induced gastric lesions was variable according to the nature of the test solution: GFSM mixture (41.1%) < polyfloral honey (55.2%) < monofloral honey (64.0%). Perfusion of the stomach with isotonic honey resulted in (1) a 70% reduction of the area of the lesions caused by ethanol, (2) the failure to prevent the transmural potential difference fall induced by ethanol, (3) an increase of basal and histamine-stimulated acid secretion. These results suggest that sugar rich solutions (GFSM and honey) may prevent gastric damage by a mechanism involving the release of some protective agents.

Survival of Viral Biowarfare Agents in Disinfected Waters

PubMed Central

Wade, Mary Margaret; Chambers, Amanda E.; Insalaco, Joseph M.; Zulich, Alan W.

2010-01-01

Protecting civilian and military water supplies has received more attention since the United States began its war on terror in 2001. Both chlorine and bromine are used by branches of the U.S. military for disinfecting water supplies; however, limited data exists as to the effectiveness of these additives when used against viral biowarfare agents. The present study sought to evaluate the survival of selected viral biothreat agents in disinfected water. Disinfected water samples were spiked with vaccinia virus strain WR and Venezuelan equine encephalitis (VEE) virus strain TC-83 each separately to a final concentration of approximately 1 × 106 PFU/mL, and survival was assessed by plaque assay. Both viruses were inactivated by 1 mg/L free available chlorine (FAC) and 2mg/L total bromine within one hour. In conclusion, these results demonstrate that both chlorine and bromine are effective disinfectants against vaccinia virus and VEE strain TC-83 at the concentrations tested. PMID:21197430

Comparison of various iron chelators and prochelators as protective agents against cardiomyocyte oxidative injury.

PubMed

Jansová, Hana; Macháček, Miloslav; Wang, Qin; Hašková, Pavlína; Jirkovská, Anna; Potůčková, Eliška; Kielar, Filip; Franz, Katherine J; Simůnek, Tomáš

2014-09-01

Oxidative stress is a common denominator of numerous cardiovascular disorders. Free cellular iron catalyzes the formation of highly toxic hydroxyl radicals, and iron chelation may thus be an effective therapeutic approach. However, using classical iron chelators in diseases without iron overload poses risks that necessitate more advanced approaches, such as prochelators that are activated to chelate iron only under disease-specific oxidative stress conditions. In this study, three cell-membrane-permeable iron chelators (clinically used deferasirox and experimental SIH and HAPI) and five boronate-masked prochelator analogs were evaluated for their ability to protect cardiac cells against oxidative injury induced by hydrogen peroxide. Whereas the deferasirox-derived agents TIP and TRA-IMM displayed negligible protection and even considerable toxicity, the aroylhydrazone prochelators BHAPI and BSIH-PD provided significant cytoprotection and displayed lower toxicity after prolonged cellular exposure compared to their parent chelators HAPI and SIH, respectively. Overall, the most favorable properties in terms of protective efficiency and low inherent cytotoxicity were observed with the aroylhydrazone prochelator BSIH. BSIH efficiently protected both H9c2 rat cardiomyoblast-derived cells and isolated primary rat cardiomyocytes against hydrogen peroxide-induced mitochondrial and lysosomal dysregulation and cell death. At the same time, BSIH was nontoxic at concentrations up to its solubility limit (600 μM) and in 72-h incubation. Hence, BSIH merits further investigation for prevention and/or treatment of cardiovascular disorders associated with a known (or presumed) component of oxidative stress. Copyright © 2014 Elsevier Inc. All rights reserved.

Recombinant Salmonella Expressing Burkholderia mallei LPS O Antigen Provides Protection in a Murine Model of Melioidosis and Glanders

PubMed Central

Moustafa, Dina A.; Scarff, Jennifer M.; Garcia, Preston P.; Cassidy, Sara K. B.; DiGiandomenico, Antonio; Waag, David M.; Inzana, Thomas J.; Goldberg, Joanna B.

2015-01-01

Burkholderia pseudomallei and Burkholderia mallei are the etiologic agents of melioidosis and glanders, respectively. These bacteria are highly infectious via the respiratory route and can cause severe and often fatal diseases in humans and animals. Both species are considered potential agents of biological warfare; they are classified as category B priority pathogens. Currently there are no human or veterinary vaccines available against these pathogens. Consequently efforts are directed towards the development of an efficacious and safe vaccine. Lipopolysaccharide (LPS) is an immunodominant antigen and potent stimulator of host immune responses. B. mallei express LPS that is structurally similar to that expressed by B. pseudomallei, suggesting the possibility of constructing a single protective vaccine against melioidosis and glanders. Previous studies of others have shown that antibodies against B. mallei or B. pseudomallei LPS partially protect mice against subsequent lethal virulent Burkholderia challenge. In this study, we evaluated the protective efficacy of recombinant Salmonella enterica serovar Typhimurium SL3261 expressing B. mallei O antigen against lethal intranasal infection with Burkholderia thailandensis, a surrogate for biothreat Burkholderia spp. in a murine model that mimics melioidosis and glanders. All vaccine-immunized mice developed a specific antibody response to B. mallei and B. pseudomallei O antigen and to B. thailandensis and were significantly protected against challenge with a lethal dose of B. thailandensis. These results suggest that live-attenuated SL3261 expressing B. mallei O antigen is a promising platform for developing a safe and effective vaccine. PMID:26148026

Recombinant Salmonella Expressing Burkholderia mallei LPS O Antigen Provides Protection in a Murine Model of Melioidosis and Glanders.

PubMed

Moustafa, Dina A; Scarff, Jennifer M; Garcia, Preston P; Cassidy, Sara K B; DiGiandomenico, Antonio; Waag, David M; Inzana, Thomas J; Goldberg, Joanna B

2015-01-01

Burkholderia pseudomallei and Burkholderia mallei are the etiologic agents of melioidosis and glanders, respectively. These bacteria are highly infectious via the respiratory route and can cause severe and often fatal diseases in humans and animals. Both species are considered potential agents of biological warfare; they are classified as category B priority pathogens. Currently there are no human or veterinary vaccines available against these pathogens. Consequently efforts are directed towards the development of an efficacious and safe vaccine. Lipopolysaccharide (LPS) is an immunodominant antigen and potent stimulator of host immune responses. B. mallei express LPS that is structurally similar to that expressed by B. pseudomallei, suggesting the possibility of constructing a single protective vaccine against melioidosis and glanders. Previous studies of others have shown that antibodies against B. mallei or B. pseudomallei LPS partially protect mice against subsequent lethal virulent Burkholderia challenge. In this study, we evaluated the protective efficacy of recombinant Salmonella enterica serovar Typhimurium SL3261 expressing B. mallei O antigen against lethal intranasal infection with Burkholderia thailandensis, a surrogate for biothreat Burkholderia spp. in a murine model that mimics melioidosis and glanders. All vaccine-immunized mice developed a specific antibody response to B. mallei and B. pseudomallei O antigen and to B. thailandensis and were significantly protected against challenge with a lethal dose of B. thailandensis. These results suggest that live-attenuated SL3261 expressing B. mallei O antigen is a promising platform for developing a safe and effective vaccine.

Biofilms in vitro and in vivo: do singular mechanisms imply cross-resistance?

PubMed

Gilbert, P; Allison, D G; McBain, A J

2002-01-01

Microbial biofilm has become inexorably linked with man's failure to control them by antibiotic and biocide regimes that are effective against suspended bacteria. This failure relates to a localized concentration of biofilm bacteria, and their extracellular products (exopolymers and extracellular enzymes), that moderates the access of the treatment agent and starves the more deeply placed cells. Biofilms, therefore, typically present gradients of physiology and concentration for the imposed treatment agent, which enables the less susceptible clones to survive. Such clones might include efflux mutants in addition to genotypes with modifications in single gene products. Clonal expansion following subeffective treatment would, in the case of many antibiotics, lead to the emergence of a resistant population. This tends not to occur for biocidal treatments where the active agent exhibits multiple pharmacological activity towards a number of specific cellular targets. Whilst resistance development towards biocidal agents is highly unlikely, subeffective exposure will lead to the selection of less susceptible clones, modified either in efflux or in their most susceptible target. The latter might also confer resistance to antibiotics where the target is shared. Thus, recent reports have demonstrated that sublethal concentrations of the antibacterial and antifungal agent triclosan can select for resistant mutants in Escherichia coli and that this agent specifically targets the enzyme enoyl reductase that is involved in lipid biosynthesis. Triclosan may, therefore, select for mutants in a target that is shared with the anti-E. coli diazaborine compounds and the antituberculosis drug isoniazid. Although triclosan may be a uniquely specific biocide, sublethal concentrations of less specific antimicrobial agents may also select for mutations within their most sensitive targets, some of which might be common to therapeutic agents. Sublethal treatment with chemical antimicrobial agents has also been demonstrated to induce the expression of multidrug efflux pumps and efflux mutants. Whilst efflux does not confer protection against use concentrations of biocidal products it is sufficient to confer protection against therapeutic doses of many antibiotics. It has, therefore, been widely speculated that biocide misuse may have an insidious effect, contributing to the evolution and persistence of drug resistance within microbial communities. Whilst such notions are supported by laboratory studies that utilize pure cultures, recent evidence has strongly refuted such linkage within the general environment where complex, multispecies biofilms predominate and where biocidal products are routinely deployed. In such situations the competition, for nutrients and space, between community members of disparate sensitivities far outweighs any potential benefits bestowed by the changes in an individual's antimicrobial susceptibility.

Personnel Attrition Rates in Historical Land Combat Operations: Susceptibility and Vulnerability of Major Anatomical Regions

DTIC Science & Technology

1993-08-01

effectiveness , estimate personnel attr;i"on, perform studies and analyses. or assess protective equipment for personnel. i II CAA-RP-93-3 DEPARTMENT OF THE...weapons or weapons effects that are difficult to localize are excluded from the 1-1 CAA-RP-93-3 scope of this paper Some examples of the types of weapons...or weapon effects excluded atr" .;i,nical weapons (encompassing war gases and other toxic substances, flame weapons. and biological agents), nuclear

Halloysite clay nanotubes for controlled release of protective agents.

PubMed

Lvov, Yuri M; Shchukin, Dmitry G; Möhwald, Helmuth; Price, Ronald R

2008-05-01

Halloysite aluminosilicate nanotubes with a 15 nm lumen, 50 nm external diameter, and length of 800 +/- 300 nm have been developed as an entrapment system for loading, storage, and controlled release of anticorrosion agents and biocides. Fundamental research to enable the control of release rates from hours to months is being undertaken. By variation of internal fluidic properties, the formation of nanoshells over the nanotubes and by creation of smart caps at the tube ends it is possible to develop further means of controlling the rate of release. Anticorrosive halloysite coatings are in development and a self-healing approach has been developed for repair mechanisms through response activation to external impacts. In this Perspective, applications of halloysite as nanometer-scale containers are discussed, including the use of halloysite tubes as drug releasing agents, as biomimetic reaction vessels, and as additives in biocide and protective coatings. Halloysite nanotubes are available in thousands of tons, and remain sophisticated and novel natural nanomaterials which can be used for the loading of agents for metal and plastic anticorrosion and biocide protection.

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis.

PubMed

Li, Hao; Wang, Xing-Xing; Wang, Bin; Fu, Lei; Liu, Guan; Lu, Yu; Cao, Min; Huang, Hairong; Javid, Babak

2017-05-09

The role of Igs in natural protection against infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb, remain healthy-make antibody responses that are effective in protecting against infection by Mtb. We tested antibodies isolated from 48 healthcare workers and compared these with 12 patients with active TB. We found that antibodies from 7 of 48 healthcare workers but none from active TB patients showed moderate protection against Mtb in an aerosol mouse challenge model. Intriguingly, three of seven healthcare workers who made protective antibody responses had no evidence of prior TB infection by IFN-γ release assay. There was also good correlation between protection observed in vivo and neutralization of Mtb in an in vitro human whole-blood assay. Antibodies mediating protection were directed against the surface of Mtb and depended on both immune complexes and CD4+ T cells for efficacy. Our results indicate that certain individuals make protective antibodies against Mtb and challenge paradigms about the nature of an effective immune response to TB.

46 CFR 185.612 - Fire protection equipment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... releasing the extinguishing agent should the local manual release or stop valve controls fail to operate... at or near each pull box and stop valve control and in the space where the extinguishing agent...-VACATE AT ONCE. CARBON DIOXIDE BEING RELEASED”. Where a different extinguishing agent is installed, that...

49 CFR 393.95 - Emergency equipment on all power units.

Code of Federal Regulations, 2012 CFR

2012-10-01

... relative to the motor vehicle. (5) Extinguishing agents. The fire extinguisher must use an extinguishing agent that does not need protection from freezing. Extinguishing agents must comply with the toxicity... transportation of Division 2.1 (flammable gas) or Class 3 (flammable liquid) hazardous materials whether loaded...

49 CFR 393.95 - Emergency equipment on all power units.

Code of Federal Regulations, 2014 CFR

2014-10-01

... relative to the motor vehicle. (5) Extinguishing agents. The fire extinguisher must use an extinguishing agent that does not need protection from freezing. Extinguishing agents must comply with the toxicity... transportation of Division 2.1 (flammable gas) or Class 3 (flammable liquid) hazardous materials whether loaded...

49 CFR 393.95 - Emergency equipment on all power units.

Code of Federal Regulations, 2013 CFR

2013-10-01

... relative to the motor vehicle. (5) Extinguishing agents. The fire extinguisher must use an extinguishing agent that does not need protection from freezing. Extinguishing agents must comply with the toxicity... transportation of Division 2.1 (flammable gas) or Class 3 (flammable liquid) hazardous materials whether loaded...

Out of Bounds

ERIC Educational Resources Information Center

Davis, Noah

2007-01-01

Due to improper contact between agents and players as well as agent infractions that have occurred and hit universities, states and colleges are increasingly turning to the courts to help protect the integrity of big-time college athletics. Universities such as Oregon now hold "agent days" to educate players about appropriate conduct. States are…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaur, Manjinder; Agarwal, Rajesh; University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, CO 80262

Failure and high systemic toxicity of conventional cancer therapies have accelerated the focus on the search for newer agents, which could prevent and/or slow-down cancer growth and have more human acceptability by being less or non-toxic. Silymarin is one such agent, which has been extensively used since ages for the treatment of liver conditions, and thus has possibly the greatest patient acceptability. In recent years, increasing body of evidence has underscored the cancer preventive efficacy of silymarin in both in vitro and in vivo animal models of various epithelial cancers. Apart from chemopreventive effects, other noteworthy aspects of silymarin andmore » its active constituent silibinin in cancer treatment include their capability to potentiate the efficacy of known chemotherapeutic drugs, as an inhibitor of multidrug resistance-associated proteins and as an adjunct to the cancer therapeutic drugs due to their organ-protective efficacy specifically liver, and immunostimulatory effects. Widespread use of silymarin for liver health in humans and commercial availability of its formulations with increased bioavailability, further underscore the necessity of carrying out controlled clinical trials with these agents in cancer patients. In this review, we will briefly discuss the outcomes of clinical trials being conducted by us and others in cancer patients to provide insight into the clinical relevance of the observed chemopreventive effects of these agents in various epithelial cancer models.« less

Nanoparticles increase the efficacy of cancer chemopreventive agents in cells exposed to cigarette smoke condensate.

PubMed

Pulliero, Alessandra; Wu, Yun; Fenoglio, Daniela; Parodi, Alessia; Romani, Massimo; Soares, Christiane P; Filaci, Gilberto; Lee, James L; Sinkam, Patrick N; Izzotti, Alberto

2015-03-01

Lung cancer is a leading cause of death in developed countries. Although smoking cessation is a primary strategy for preventing lung cancer, former smokers remain at high risk of cancer. Accordingly, there is a need to increase the efficacy of lung cancer prevention. Poor bioavailability is the main factor limiting the efficacy of chemopreventive agents. The aim of this study was to increase the efficacy of cancer chemopreventive agents by using lipid nanoparticles (NPs) as a carrier. This study evaluated the ability of lipid NPs to modify the pharmacodynamics of chemopreventive agents including N-acetyl-L-cysteine, phenethyl isothiocyanate and resveratrol (RES). The chemopreventive efficacy of these drugs was determined by evaluating their abilities to counteract cytotoxic damage (DNA fragmentation) induced by cigarette smoke condensate (CSC) and to activate protective apoptosis (annexin-V cytofluorimetric staining) in bronchial epithelial cells both in vitro and in ex vivo experiment in mice. NPs decreased the toxicity of RES and increased its ability to counteract CSC cytotoxicity. NPs significantly increased the ability of phenethyl isothiocyanate to attenuate CSC-induced DNA fragmentation at the highest tested dose. In contrast, this potentiating effect was observed at all tested doses of RES, NPs dramatically increasing RES-induced apoptosis in CSC-treated cells. These results provide evidence that NPs are highly effective at increasing the efficacy of lipophilic drugs (RES) but are not effective towards hydrophilic agents (N-acetyl-L-cysteine), which already possess remarkable bioavailability. Intermediate effects were observed for phenethyl isothiocyanate. These findings are relevant to the identification of cancer chemopreventive agents that would benefit from lipid NP delivery. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Development of practical methods for removal of radiological, biological, and chemical contaminants from water supplies. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woodward, R.L.; Robeck, G.G.

1958-06-01

Laboratory and engineering studies were conducted to determine the design criteria and cost estimated of providing and operating devices to protect against radiological, biological and chemical warfare agents that may contaminate shore based Naval water supplies. Small disposable columns of mixed cation-anion exchange resins will remove the soluble radionuclides enough to suffice for immediate drinking and culinary purposes. Chemical warfare agents are so numerous and varied that it is not feasible to provide a single protective device to cope with them. Chlorination with free available chlorine residuals of 1 mg liter will handle most biological warfare agents.

Biodefense and Bioterrorism

MedlinePlus

... to cause disease, spread, or resist medical treatment. Biological agents spread through the air, water, or in ... viruses, plague, or smallpox could be used as biological agents. Biodefense uses medical measures to protect people ...

Chrysin alleviates testicular dysfunction in adjuvant arthritic rats via suppression of inflammation and apoptosis: Comparison with celecoxib

DOE Office of Scientific and Technical Information (OSTI.GOV)

Darwish, Hebatallah A.; Arab, Hany H., E-mail: hany.arab@pharma.cu.edu.eg; Abdelsalam, Rania M.

Long standing rheumatoid arthritis (RA) is associated with testicular dysfunction and subfertility. Few studies have addressed the pathogenesis of testicular injury in RA and its modulation by effective agents. Thus, the current study aimed at evaluating the effects of two testosterone boosting agents; chrysin, a natural flavone and celecoxib, a selective COX-2 inhibitor, in testicular impairment in rats with adjuvant arthritis, an experimental model of RA. Chrysin (25 and 50 mg/kg) and celecoxib (5 mg/kg) were orally administered to Wistar rats once daily for 21 days starting 1 h before arthritis induction. Chrysin suppressed paw edema with comparable efficacy tomore » celecoxib. More important, chrysin, dose-dependently and celecoxib attenuated the testicular injury via reversing lowered gonadosomatic index and histopathologic alterations with preservation of spermatogenesis. Both agents upregulated steroidogenic acute regulatory (StAR) mRNA expression and serum testosterone with concomitant restoration of LH and FSH. Furthermore, they suppressed inflammation via abrogation of myeloperoxidase, TNF-α and protein expression of COX-2 and iNOS besides elevation of IL-10. Alleviation of the testicular impairment was accompanied with suppression of oxidative stress via lowering testicular lipid peroxides and nitric oxide. With respect to apoptosis, both agents downregulated FasL mRNA expression and caspase-3 activity in favor of cell survival. For the first time, these findings highlight the protective effects of chrysin and celecoxib against testicular dysfunction in experimental RA which were mediated via boosting testosterone in addition to attenuation of testicular inflammation, oxidative stress and apoptosis. Generally, the 50 mg/kg dose of chrysin exerted comparable protective actions to celecoxib. - Highlights: • Chrysin and celecoxib alleviated testicular suppression in adjuvant arthritis. • They attenuated histopathological damage and preserved spermatogenesis. • They upregulated StAR expression and testosterone with restoration of LH and FSH. • They abrogated myeloperoxidase, TNF-α and COX-2 and iNOS expression. • They suppressed oxidative stress and FasL-associated apoptosis.« less

Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response.

PubMed

Sikiric, P; Seiwerth, S; Brcic, L; Blagaic, A B; Zoricic, I; Sever, M; Klicek, R; Radic, B; Keller, N; Sipos, K; Jakir, A; Udovicic, M; Tonkic, A; Kokic, N; Turkovic, B; Mise, S; Anic, T

2006-12-01

Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, safe in clinical trials for inflammatory bowel disease (PL 10, PLD 116, PLD 14736, Pliva, Croatia)) has a particular cytoprotective/adaptive cytoprotective activity. The cytoprotective/adaptive cytoprotection researches largely neglect that stomach distension could per se jeopardize the mucosal integrity, with constantly stretched mucosa and blood vessels, and sphincters more prone for reflux induction. After absolute alcohol instillation in fully distended rat stomach, gastric, esophageal and duodenal lesions occur. Throughout next 3 min, left gastric artery blood vessels clearly disappear at the serosal site, indicative for loss of vessels both integrity and function. Contrary, constant vessels presentation could predict the beneficial effect of applied agent. After pentadecapeptide BPC 157 instillation into the stomach the vessels presentation remains constant, and lesions of stomach, esophagus, and duodenum are inhibited. Standards (atropine, ranitidine, omeprazole) could only slightly improve the vessels presentation compared to control values, and they have only a partial effect on the lesions. In this review we emphasize BPC 157 unusual stability, and some of its important effects: effectiveness against various lesions in gastrointestinal tract, on nitric oxide (NO)-system, and NO-agents effects, on somatosensory neurons, salivary glands function, recovery of AMP-ADP-ATP system, endothelium protection, effect on endothelin, and on angiogenesis promotion. It also antagonizes other alcohol effects, including acute and chronic intoxication. Given peripherally, it counteracts the consequence of central dopamine system disturbances (receptor blockade), and induces serotonin release in substantia nigra. Therapeutic potential of BPC 157 as a cytoprotective agent is also seen in its capability to heal various wounds. Given directly into the stomach, BPC 157 instantly recovers disturbed lower esophageal and pyloric sphincter pressure in rats after 12-20 months of untreated esophagitis. All these could be suggestive for its role as a natural protectant in gastric juice with particular function throughout stomach distension.

Civilian exposure to toxic agents: emergency medical response.

PubMed

Baker, David

2004-01-01

Civilian populations are at risk from exposure to toxic materials as a result of accidental or deliberate exposure. In addition to industrial hazards, toxic agents designed for use in warfare now are a potential hazard in everyday life through terrorist action. Civil emergency medical responders should be able to adapt their plans for dealing with casualties from hazardous materials (HazMat) to deal with the new threat. Chemical and biological warfare (CBW) and HazMat agents can be viewed as a continuous spectrum. Each of these hazards is characterized by qualities of toxicity, latency of action, persistency, and transmissibility. The incident and medical responses to release of any agent is determined by these characteristics. Chemical and biological wardare agents usually are classified as weapons of mass destruction, but strictly, they are agents of mass injury. The relationship between mass injury and major loss of life depends very much on the protection, organization, and emergency care provided. Detection of a civil toxic agent release where signs and symptoms in casualties may be the first indicator of exposure is different from the military situation where intelligence information and tuned detection systems generally will be available. It is important that emergency medical care should be given in the context of a specific action plan. Within an organized and protected perimeter, triage and decontamination (if the agent is persistent) can proceed while emergency medical care is provided at the same time. The provision of advanced life support (TOXALS) in this zone by protected and trained medical responders now is technically feasible using specially designed ventilation equipment. Leaving life support until after decontamination may have fatal consequences. Casualties from terrorist attacks also may suffer physical as well as toxic trauma and the medical response also should be capable of dealing with mixed injuries.

Antioxidant kinetics of plant-derived substances and extracts.

PubMed

Silva, A R; Menezes, P F C; Martinello, T; Novakovich, G F L; Praes, C E O; Feferman, I H S

2010-02-01

The antioxidant activity (AA) of substances present in several plant species has been widely studied which reflects their fundamental role in the protection of skin tissue against the harmful action of reactive oxygen species. Given the importance of effective and long-lasting protection against ultraviolet radiation, we studied the AA of several plant derivatives and extracts over time. Several chemical in vitro methods may be used to evaluate antioxidant capability, among which the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method stands out, despite its unspecificity, as the most cited and described method in the literature. In this work the AA was evaluated by measuring their capacity to reduce DPPH in 30 min, which is suggested in the literature, and additionally at different times up to 8 h from the baseline reading. The methodology used to evaluate the AA over time was validated. It is important to emphasize that this study proposes to modify the conventional DPPH method, although considered to be non-specific, to be used to test new antioxidant agents. This represents a considerable advantage because some substances show no significant activity during the first 30 min of reaction. Among other plant products, we tested a proantocyanidin-rich grapeseed extract, a hesperidin derivative, a rutin-containing ginkgo extract, a polyphenol-containing yerba maté extract and tocopheryl acetate, all of which were properly standardized. As they have different antioxidant profiles, each ingredient showed a specific behaviour over time, which may promote the selection of anti-radical compounds capable of offering protection against external agents. Combining extracts and plant derivatives that present fast, medium and slow antioxidant kinetic it is possible to create complexes capable of offering an effective protection from the moment of application up to several hours later. It is a perfectly feasible method, and such combinations prove to be more effective and have more durable effect.

The protective effect of 2-mercaptoethane sulfonate (MESNA) against traumatic brain injury in rats.

PubMed

Yilmaz, Erdal Resit; Kertmen, Hayri; Gürer, Bora; Kanat, Mehmet Ali; Arikok, Ata Türker; Ergüder, Berrin Imge; Hasturk, Askin Esen; Ergil, Julide; Sekerci, Zeki

2013-01-01

The agent, 2-mercaptoethane sulfonate (MESNA), is a synthetic small molecule, widely used as a systemic protective agent against chemotherapy toxicity, but is primarily used to reduce hemorrhagic cystitis induced by cyclophosphamide. Because MESNA has potential antioxidant and cytoprotective effects, so we hypothesized that MESNA may protect the brain against traumatic injury. Thirty-two rats were randomized into four groups of eight animals each; Group 1 (sham), Group 2 (trauma), Group 3 (150 mg/kg MESNA), Group 4 (30 mg/kg methylprednisolone). Only skin incision was performed in the sham group. In all the other groups, the traumatic brain injury model was created by an object weighing 450 g falling freely from a height of 70 cm through a copper tube on to the metal disc over the skull. The drugs were administered immediately after the injury. The animals were killed 24 h later. Brain tissues were extracted for analysis, where levels of tissue malondialdehyde, caspase-3, glutathione peroxidase, superoxide dismutase, nitric oxide, nitric oxide synthetase and xanthine oxidase were analyzed. Also, histopathological evaluation of the tissues was performed. After head trauma, tissue malondialdehyde levels increased; these levels were significantly decreased by MESNA administration. Caspase-3 levels were increased after trauma, but no effect of MESNA was determined in caspase-3 activity. Following trauma, both glutathione peroxidase and superoxide dismutase levels were decreased; MESNA increased the activity of both these antioxidant enzymes. Also, after trauma, nitric oxide, nitric oxide synthetase and xanthine oxidase levels were increased; administration of MESNA significantly decreased the levels of nitric oxide, nitric oxide synthetase and xanthine oxidase, promising an antioxidant activity. Histopathological analysis showed that MESNA protected the brain tissues well from injury. Although further studies considering different dose regimens and time intervals are required, MESNA was shown to be at least as effective as methylprednisolone in the traumatic brain injury model.

14 CFR 23.863 - Flammable fluid fire protection.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Flammable fluid fire protection. 23.863... Construction Fire Protection § 23.863 Flammable fluid fire protection. (a) In each area where flammable fluids... fluids, shutting down equipment, fireproof containment, or use of extinguishing agents. (5) Ability of...

14 CFR 23.863 - Flammable fluid fire protection.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Flammable fluid fire protection. 23.863... Construction Fire Protection § 23.863 Flammable fluid fire protection. (a) In each area where flammable fluids... fluids, shutting down equipment, fireproof containment, or use of extinguishing agents. (5) Ability of...

14 CFR 23.863 - Flammable fluid fire protection.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Flammable fluid fire protection. 23.863... Construction Fire Protection § 23.863 Flammable fluid fire protection. (a) In each area where flammable fluids... fluids, shutting down equipment, fireproof containment, or use of extinguishing agents. (5) Ability of...

14 CFR 23.863 - Flammable fluid fire protection.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Flammable fluid fire protection. 23.863... Construction Fire Protection § 23.863 Flammable fluid fire protection. (a) In each area where flammable fluids... fluids, shutting down equipment, fireproof containment, or use of extinguishing agents. (5) Ability of...

Protection against trichothecene mycotoxins. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1983-01-01

Trichothecene mycotoxins, produced by certain fungi found in cereal grains, are a significant health problem in agricultural settings and have been detected throughout the world. Concern about the reported use of trichothecenes in chemical warfare agents, or 'yellow rain,' led the U.S. Army to request that the National Research Council form a committee on protection against mycotoxins, to study the effects of trichothecenes on civilians and military personnel who might be exposed to high levels of these substances. The report discusses scientific questions about the natural occurrences of mycotoxins, methods of detection and quantitation, decontamination and detoxification, long-term environmental effects,more » effects on humans and animals, and strategies for prevention and treatment. It also recommends areas of research that are particularly promising. An extensive bibliography is included.« less

Is substance P released from slices of the rat spinal cord inactivated by peptidase(s) distinct from both 'enkephalinase' and 'angiotensin-converting enzyme'?

PubMed

Mauborgne, A; Bourgoin, S; Benoliel, J J; Hamon, M; Cesselin, F

1991-02-25

Studies on the effects of peptidase inhibitors on substance P-like immunoreactive material (SPLI) released by K(+)-induced depolarization from slices of the rat spinal cord showed that bacitracin was the most potent agent to protect SPLI from degradation. Captopril and thiorphan which inhibit, respectively, angiotensin I converting enzyme and endopeptidase-24.11 also protected SPLI from degradation. However other inhibitors of these two enzymes, kelatorphan for endopeptidase-24.11 and enalaprilat for angiotensin I converting enzyme were essentially inactive, indicating that both enzymes are probably not involved in the degradation of endogenous substance P. Instead, the non-additive protecting effect of bacitracin, captopril and thiorphan might be due to the blockade of some 'bacitracin-sensitive enzyme' playing a key role in the catabolism of SP within the rat spinal cord.

Advances in analytical technologies for environmental protection and public safety.

PubMed

Sadik, O A; Wanekaya, A K; Andreescu, S

2004-06-01

Due to the increased threats of chemical and biological agents of injury by terrorist organizations, a significant effort is underway to develop tools that can be used to detect and effectively combat chemical and biochemical toxins. In addition to the right mix of policies and training of medical personnel on how to recognize symptoms of biochemical warfare agents, the major success in combating terrorism still lies in the prevention, early detection and the efficient and timely response using reliable analytical technologies and powerful therapies for minimizing the effects in the event of an attack. The public and regulatory agencies expect reliable methodologies and devices for public security. Today's systems are too bulky or slow to meet the "detect-to-warn" needs for first responders such as soldiers and medical personnel. This paper presents the challenges in monitoring technologies for warfare agents and other toxins. It provides an overview of how advances in environmental analytical methodologies could be adapted to design reliable sensors for public safety and environmental surveillance. The paths to designing sensors that meet the needs of today's measurement challenges are analyzed using examples of novel sensors, autonomous cell-based toxicity monitoring, 'Lab-on-a-Chip' devices and conventional environmental analytical techniques. Finally, in order to ensure that the public and legal authorities are provided with quality data to make informed decisions, guidelines are provided for assessing data quality and quality assurance using the United States Environmental Protection Agency (US-EPA) methodologies.

Highly oxidized graphene oxide and methods for production thereof

DOEpatents

Tour, James M.; Kosynkin, Dmitry V.

2016-08-30

A highly oxidized form of graphene oxide and methods for production thereof are described in various embodiments of the present disclosure. In general, the methods include mixing a graphite source with a solution containing at least one oxidant and at least one protecting agent and then oxidizing the graphite source with the at least one oxidant in the presence of the at least one protecting agent to form the graphene oxide. Graphene oxide synthesized by the presently described methods is of a high structural quality that is more oxidized and maintains a higher proportion of aromatic rings and aromatic domains than does graphene oxide prepared in the absence of at least one protecting agent. Methods for reduction of graphene oxide into chemically converted graphene are also disclosed herein. The chemically converted graphene of the present disclosure is significantly more electrically conductive than is chemically converted graphene prepared from other sources of graphene oxide.

Evaluation of protective effect of amifostine on dacarbazine induced genotoxicity.

PubMed

Etebari, M; Jafarian-Dehkordi, A; Lame, V

2015-01-01

Anticancer therapy with alkylating agents has been used for many years. Dacarbazine (DTIC) as an alkylating agent is used alone or in combination with other chemotherapy drugs. In order to inhibit the formation of secondary cancers resulting from chemotherapy with DTIC, preventional strategies is necessary. The present study was undertaken to evaluate the genoprotective effect of amifostine on the genotoxic effects of DTIC in cell culture condition. To determine the optimum genotoxic concentration of DTIC, HepG2 cells were incubated with various DTIC concentrations including 5, 10 and 20 μg/ml for 2 h and the genotoxic effects were evaluated by the comet assay. The result of this part of the study showed that incubation of HepG2 cells with DTIC at 5 μg/ml was sufficient to produce genotoxic effect. In order to determine the protective effects of amifostine on genotoxicity induced by DTIC, HepG2 cells were incubated with different concentrations of amifostine (2, 3 and 5 mg/ml) for 1 h which was followed by incubation with DTIC at 5 μg/ml for 2 h. One hour incubation of cells with different concentrations of amifostine before incubation with DITC indicated that at least 5 mg/ml concentration of amifostine can prevent genotoxic effects induced by DTIC on HepG2 cells under described condition. In conclusion amifostine could prevent DNA damage induced by DTIC on HepG2 cells.

Allium vegetables and organosulfur compounds: do they help prevent cancer?

PubMed Central

Bianchini, F; Vainio, H

2001-01-01

Allium vegetables have been shown to have beneficial effects against several diseases, including cancer. Garlic, onions, leeks, and chives have been reported to protect against stomach and colorectal cancers, although evidence for a protective effect against cancer at other sites, including the breast, is still insufficient. The protective effect appears to be related to the presence of organosulfur compounds and mainly allyl derivatives, which inhibit carcinogenesis in the forestomach, esophagus, colon, mammary gland, and lung of experimental animals. The exact mechanisms of the cancer-preventive effects are not clear, although several hypotheses have been proposed. Organosulfur compounds modulate the activity of several metabolizing enzymes that activate (cytochrome P450s) or detoxify (glutathione S-transferases) carcinogens and inhibit the formation of DNA adducts in several target tissues. Antiproliferative activity has been described in several tumor cell lines, which is possibly mediated by induction of apoptosis and alterations of the cell cycle. Allium vegetables and organosulfur compounds are thus possible cancer-preventive agents. Clinical trials will be required to define the effective dose that has no toxicity in humans. PMID:11673117

Organosulfur compounds and possible mechanism of garlic in cancer

PubMed Central

Omar, S.H.; Al-Wabel, N.A.

2009-01-01

Garlic (Allium sativum), a member of the family Liliaceae, contains an abundance of chemical compounds that have been shown to possess beneficial effects to protect against several diseases, including cancer. Evidence supports the protective effects of garlic in stomach, colorectal, breast cancer in humans. The protective effects appear to be related to the presence of organosulfur compounds, predominantly allyl derivatives, which also have been shown to inhibit carcinogenesis in forestomach, esophagus, colon, mammary gland and lung of experimental animals. The exact mechanisms of the cancer-preventive effects are not clear, although several hypotheses have been proposed. Organosulfur compounds modulate the activity of several metabolizing enzymes that activate (cytochrome P450s) or detoxify (glutathione S-transferases) carcinogens and inhibit the formation of DNA adducts in several target tissues. Antiproliferative activity has been described in several tumor cell lines, which is possibly mediated by induction of apoptosis and alterations of the cell cycle. Organosulfur compounds in garlic are thus possible cancer-preventive agents. Clinical trials will be required to define the effective dose that has no toxicity in humans. PMID:23960721

Allium vegetables and organosulfur compounds: do they help prevent cancer?

PubMed

Bianchini, F; Vainio, H

2001-09-01

Allium vegetables have been shown to have beneficial effects against several diseases, including cancer. Garlic, onions, leeks, and chives have been reported to protect against stomach and colorectal cancers, although evidence for a protective effect against cancer at other sites, including the breast, is still insufficient. The protective effect appears to be related to the presence of organosulfur compounds and mainly allyl derivatives, which inhibit carcinogenesis in the forestomach, esophagus, colon, mammary gland, and lung of experimental animals. The exact mechanisms of the cancer-preventive effects are not clear, although several hypotheses have been proposed. Organosulfur compounds modulate the activity of several metabolizing enzymes that activate (cytochrome P450s) or detoxify (glutathione S-transferases) carcinogens and inhibit the formation of DNA adducts in several target tissues. Antiproliferative activity has been described in several tumor cell lines, which is possibly mediated by induction of apoptosis and alterations of the cell cycle. Allium vegetables and organosulfur compounds are thus possible cancer-preventive agents. Clinical trials will be required to define the effective dose that has no toxicity in humans.

Cinnamon (Cinnamomum zeylanicum) as an antidote or a protective agent against natural or chemical toxicities: a review.

PubMed

Dorri, Mahyar; Hashemitabar, Shirin; Hosseinzadeh, Hossein

2018-01-10

Cinnamon (Cinnamomum zeylanicum, Lauraceae) is a food additive greatly used for its taste. However, recently this medicinal plant has been brought to attention due to its medical effects. Cinnamon has constituents such as cinnamaldehyde and cinnamic acid that offers some health benefits including antioxidant and free-radical scavenging properties, lowering of blood glucose, anti-cholesterolemic, analgesic, antimicrobial, anti-inflammatory, anti-yeast, anti-secretagogue, and anti-gastric ulcer effects. This review summarizes various in vitro and animal studies on the protective effects of cinnamon against natural and chemical toxins. These studies consider the antidotal and/or protective effects of cinnamon and its major constituents against natural toxins and chemical-induced toxicities. It has been mentioned that cinnamon and its main constituents can ameliorate the toxicity of chemical toxins in liver, kidney, blood, brain, embryo, reproductive system, heart, spleen in part through antioxidant effect, radical scavenging, reducing lipid peroxidation, anti-inflammatory, fungistatic and fungicidal activities, modulation of CK-MB, LDH, TNF-α, IL-6, mitogen-activated protein kinase (MAPK), and nuclear factor-ĸB (NF-ĸB) signaling pathways.

Agentic personality characteristics and coping: their relation to trait anxiety in college students.

PubMed

Weigold, Ingrid K; Robitschek, Christine

2011-04-01

Anxiety and its disorders, often present before adulthood, have high personal and societal costs for men and women. This study tested a mediation model in which 3 forms of coping mediate the relation of 3 agentic personality characteristics (i.e., traits associated with the belief that people can effectively exercise control over their lives) to lower levels of anxiety within 1 subgroup of young adults (i.e., college students). The agentic personality characteristics were (a) hardiness, (b) personal growth initiative, and (c) coping self-efficacy. The forms of dispositional coping were (a) problem-focused, (b) emotion-focused, and (c) avoidant. Results suggest that agentic personality characteristics differentially relate to forms of coping and trait anxiety. In addition, coping appears to fully mediate the relations of the personality characteristics to anxiety. The results imply that agentic personality characteristics and coping are important in decreasing and/or protecting against anxiety, in part because of how they relate to forms of coping, and suggest the need for more research. © 2011 American Orthopsychiatric Association.

The role of isoflavone metabolism in plant protection depends on the rhizobacterial MAMP that triggers systemic resistance against Xanthomonas axonopodis pv. glycines in Glycine max (L.) Merr. cv. Osumi.

PubMed

Algar, Elena; Gutierrez-Mañero, F Javier; Garcia-Villaraco, Ana; García-Seco, Daniel; Lucas, J Antonio; Ramos-Solano, Beatriz

2014-09-01

Glycine max (L.) Merr. plays a crucial role in both the field of food and the pharmaceutical industry due to their input as plant protein and to the benefits of isoflavones (IF) for health. In addition, IF play a key role in nodulation and plant defense and therefore, an increase in IF would be desirable for better field performance. IF are secondary metabolites and therefore, inducible, so finding effective agents to increase IF contents is interesting. Among these agents, plant growth promoting rhizobacteria (PGPR) have been used to trigger systemic induction of plant's secondary metabolism through their microbe associated molecular patterns (MAMPs) that fit in the plant's receptors to start a systemic response. The aim of this study was to evaluate the ability of 4 PGPR that had a contrasted effect on IF metabolism, to protect plants against biotic stress and to establish the relation between IF profile and the systemic response triggered by the bacteria. Apparently, the response involves a lower sensitivity to ethylene and despite the decrease in effective photosynthesis, growth is only compromised in the case of M84, the most effective in protection. All strains protected soybean against Xanthomonas axonopodis pv. glycines (M84 > N5.18 > Aur9>N21.4) and only M84 and N5.18 involved IF. N5.18 stimulated accumulation of IF before pathogen challenge. M84 caused a significant increase on IF only after pathogen challenge and N21.4 caused a significant increase on IF content irrespective of pathogen challenge. Aur9 did not affect IF. These results point out that all 4 strains have MAMPs that trigger defensive metabolism in soybean. Protection induced by N21.4 and Aur9 involves other metabolites different to IF and the role of IF in defence depends on the previous metabolic status of the plant and on the bacterial MAMP. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Adenovirus-Mediated Gene Therapy Against Viral Biothreat Agents

DTIC Science & Technology

2016-04-12

economy. Vaccine development is an important strategy to thwart the threat of these viral biothreat agents. There is an urgent need to improve...Alberta, Tl A 8K6. Canada E-mail: josh. wu@drdc-rddc.gc.ca .• 78 JoshQ.H. Wu existing vaccines against these agents and to develop new ones. Gene...of vaccines against viral biothreat agents. Genes encoding protective antigens of viral biothreat agents can be carried by these viral vectors and

Protective effects of skin permeable epidermal and fibroblast growth factor against ultraviolet-induced skin damage and human skin wrinkles.

PubMed

An, Jae Jin; Eum, Won Sik; Kwon, Hyuck Se; Koh, Jae Sook; Lee, Soo Yun; Baek, Ji Hwoon; Cho, Yong-Jun; Kim, Dae Won; Han, Kyu Huyng; Park, Jinseu; Jang, Sang Ho; Choi, Soo Young

2013-12-01

Epidermal and fibroblast growth factor (EGF and FGF1) proteins play an important role in the regeneration and proliferation of skin cells. EGF and FGF1 have considerable potential as possible therapeutic or cosmetic agents for the treatment of skin damage including wrinkles. Using protein transduction domains (PTD), we investigated whether PTD-EGF and FGF1 transduced into skin cells and tissue. Transduced proteins showed protective effects in a UV-induced skin damage model as well as against skin wrinkles. Transduced PTD-EGF and FGF1 proteins were detected by immunofluorescence and immunohistochemistry. The effects of PTD-EGF and FGF1 were examined by WST assay, Western blotting, immunohistochemistry, and skin wrinkle parameters. The PTD-EGF and FGF1 increased cell proliferation and collagen type 1 alpha 1 protein accumulation in skin tissue. Also, PTD-EGF and FGF1 inhibited UV-induced skin damage. Furthermore, topical application of PTD-EGF and FGF1 contained ampoules which were considered to improve the wrinkle parameters of human skin. These results show that PTD-EGF and FGF1 can be a potential therapeutic or cosmetic agent for skin damaged and injury including wrinkles and aging. © 2013 Wiley Periodicals, Inc.

Therapeutic equivalence of two formulations of calcipotriol-betamethasone ointment: a multi-centre, randomized, double-blind study in adult patients with chronic plaque psoriasis.

PubMed

Habjanic, N; Koytchev, R; Yankova, R; Kerec-Kos, M; Grabnar-Peklar, D

2018-06-26

Topical agents are the first-line therapy for psoriasis and treatment of choice for mild to moderate chronic plaque psoriasis. Patients with severe psoriasis often use topical therapies at least for selected body areas. 1,2 Corticosteroids and vitamin D analogues are effective, commonly used topical therapies for mild to moderate plaque psoriasis and are often used in combination due to their complementary pharmacodynamic activities. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Human health risk assessment database, "the NHSRC toxicity value database": supporting the risk assessment process at US EPA's National Homeland Security Research Center.

PubMed

Moudgal, Chandrika J; Garrahan, Kevin; Brady-Roberts, Eletha; Gavrelis, Naida; Arbogast, Michelle; Dun, Sarah

2008-11-15

The toxicity value database of the United States Environmental Protection Agency's (EPA) National Homeland Security Research Center has been in development since 2004. The toxicity value database includes a compilation of agent property, toxicity, dose-response, and health effects data for 96 agents: 84 chemical and radiological agents and 12 biotoxins. The database is populated with multiple toxicity benchmark values and agent property information from secondary sources, with web links to the secondary sources, where available. A selected set of primary literature citations and associated dose-response data are also included. The toxicity value database offers a powerful means to quickly and efficiently gather pertinent toxicity and dose-response data for a number of agents that are of concern to the nation's security. This database, in conjunction with other tools, will play an important role in understanding human health risks, and will provide a means for risk assessors and managers to make quick and informed decisions on the potential health risks and determine appropriate responses (e.g., cleanup) to agent release. A final, stand alone MS ACESSS working version of the toxicity value database was completed in November, 2007.

STUDY OF THE RADIATION-PROTECTIVE ACTION OF SOME PROTECTIVE MATERIALS ON PROTOZOA (in Russian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graevskii, E.Ya.; Nekrasova, I.V.; Shul'mina, A.I.

1962-01-01

The behavior of thiourea derivatives as protective agents during the irradiation of protozoa were investigated together with heroin which possesses a known ability of reducing the radiation reaction of tissues in aqueous solution. It was attempted to determine the effect of toxicity of the radiolytic products and of the medium itself. Cultures of Paramaecium caudatum were used for determining the ef fect of aminoethylisothiuronium bromide hydrobromide, cysteine amine, cystine amine, and heroin. The H/sub 2/Osub 2/ formed during the radiolysis was determined by titration with KMnO/sub 4/. After exposure of the protozea to 100 kr, a protective action was notedmore » by the aminoethylisothiuronium bromide hydrobromide and cystine amine. The lack of efficiency of the cysteine amine is due to its decomposition by radiolysis. (TTT)« less

Protective effects of tenuigenin on Staphylococcus aureus-induced pneumonia in mice.

PubMed

Yu, Bin; Qiao, Jiutao; Shen, Yongbin; Li, Lianyong

2017-09-01

Pneumonia is the leading cause of death in infants and young children. Staphylococcus aureus (S.aureus) is one of the most important bacteria that leads to pneumonia. Tenuigenin (TGN), a major active component isolated from the root of the Chinese herb Polygala tenuifolia, has been known to have anti-inflammatory effect. In this study, we aimed to investigate the protective effects of TGN on S.aureus-induced pneumonia in mice. The results showed that TGN significantly attenuated S.aureus-induced lung histopathological changes. TGN also inhibited lung wet/dry (W/D) ratio, and inflammatory cytokines TNF-α and IL-1β production. Furthermore, S.aureus-induced NF-κB activation was significantly inhibited by the treatment of TGN. In conclusion, the results of this study showed that TGN protected against S.aureus-induced pneumonia by inhibiting NF-κB activation. TGN might be a potential agent in the treatment of pneumonia induced by S.aureus. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Effects of Boron on Arsenic-Induced Lipid Peroxidation and Antioxidant Status in Male and Female Rats.

PubMed

Kucukkurt, Ismail; Ince, Sinan; Demirel, Hasan Huseyin; Turkmen, Ruhi; Akbel, Erten; Celik, Yasemin

2015-12-01

The aim of the present study was to investigate the possible protective effects of boron, an antioxidant agent, against arsenic-induced oxidative stress in male and female rats. In total, 42 Wistar albino male and female rats were divided into three equal groups: The animals in the control group were given normal drinking water, the second group was given drinking water with 100 mg/L arsenic, and the third group was orally administered drinking water with 100 mg/kg boron together with arsenic. At the end of the 28-day experiment, arsenic increased lipid peroxidation and damage in the tissues of rats. However, boron treatment reversed this arsenic-induced lipid peroxidation and activities of antioxidant enzymes in rats. Moreover, boron exhibited a protective action against arsenic-induced histopathological changes in the tissues of rats. In conclusion, boron was found to be effective in protecting rats against arsenic-induced lipid peroxidation by enhancing antioxidant defense mechanisms. © 2015 Wiley Periodicals, Inc.

Stabilization of anthocyanins in blackberry juice by glutathione fortification.

PubMed

Stebbins, Nathan B; Howard, Luke R; Prior, Ronald L; Brownmiller, Cindi; Mauromoustakos, Andy

2017-10-18

Blackberry anthocyanins provide attractive color and antioxidant activity. However, anthocyanins degrade during juice processing and storage, so maintaining high anthocyanin concentrations in berry juices may lead to greater antioxidant and health benefits for the consumer. This study evaluated potential additives to stabilize anthocyanins during blackberry juice storage. The anthocyanin stabilizing agents used were: glutathione, galacturonic acid, diethylenetriaminepentaacetic acid and tannic acid, which were added at a level of 500 mg L -1 . Juice anthocyanin, flavonol, and ellagitannin content and percent polymeric color were measured over five weeks of accelerated storage at 30 °C. Glutathione had the greatest protective effect on total anthocyanins and polymeric color. Therefore a second study was performed with glutathione in combination with lipoic and ascorbic acids in an effort to use antioxidant recycling to achieve a synergistic effect. However, the antioxidant recycling system had no protective effect relative to glutathione alone. Glutathione appears to be a promising blackberry juice additive to protect against anthocyanin degradation during storage.

Effect of poly-α, γ, L-glutamic acid as a capping agent on morphology and oxidative stress-dependent toxicity of silver nanoparticles

PubMed Central

Stevanović, Magdalena; Kovačević, Branimir; Petković, Jana; Filipič, Metka; Uskoković, Dragan

2011-01-01

Highly stable dispersions of nanosized silver particles were synthesized using a straightforward, cost-effective, and ecofriendly method. Nontoxic glucose was utilized as a reducing agent and poly-α, γ, L-glutamic acid (PGA), a naturally occurring anionic polymer, was used as a capping agent to protect the silver nanoparticles from agglomeration and render them biocompatible. Use of ammonia during synthesis was avoided. Our study clearly demonstrates how the concentration of the capping agent plays a major role in determining the dimensions, morphology, and stability, as well as toxicity of a silver colloidal solution. Hence, proper optimization is necessary to develop silver colloids of narrow size distribution. The samples were characterized by Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, and zeta potential measurement. MTT assay results indicated good biocompatibility of the PGA-capped silver nanoparticles. Formation of intracellular reactive oxygen species was measured spectrophotometrically using 2,7-dichlorofluorescein diacetate as a fluorescent probe, and it was shown that the PGA-capped silver nanoparticles did not induce intracellular formation of reactive oxygen species. PMID:22131829

Synergistic effect of enterocin AS-48 in combination with outer membrane permeabilizing treatments against Escherichia coli O157:H7.

PubMed

Ananou, S; Gálvez, A; Martínez-Bueno, M; Maqueda, M; Valdivia, E

2005-01-01

To determine the effects of outer membrane (OM) permeabilizing agents on the antimicrobial activity of enterocin AS-48 against Escherichia coli O157:H7 CECT 4783 strain in buffer and apple juice. We determined the influence of pH, EDTA, sodium tripolyphosphate (STPP) and heat on E. coli O157:H7 CECT 4783 sensitivity to enterocin AS-48 in buffer and in apple juice. Enterocin AS-48 was not active against intact cells of E. coli O157:H7 CECT 4783 at neutral pH. However, cells sublethally injured by OM permeabilizing agents (EDTA, STPP, pH 5, pH 8.6 and heat) became sensitive to AS-48, decreasing the amount of bacteriocin required for inhibition of E. coli O157:H7 CECT 4783. The results presented indicate that enterocin AS-48 could potentially be applied with a considerably wider range of protective agents, such as OM permeabilizing agents, with increased efficacy in inhibiting E. coli O157:H7. Results from this study support the potential use of enterocin AS-48 to control E. coli O157:H7 in combination with other hurdles.

The synergistic effect of maltose enhances the anti-melanogenic activity of acarbose.

PubMed

Bin, Bum-Ho; Kim, Sung Tae; Bhin, Jinhyuk; Byoun, Kyounghee; Lee, Tae Ryong; Cho, Eun-Gyung

2017-04-01

Melanocytes play an important role in maintaining epidermal homeostasis by producing melanin and protecting the skin from harmful environmental factors. However, excessive up- or down-regulation of melanin production often causes hyper- or hypo-pigmented disorders, respectively, which affect the patient's quality of life. Therefore, various strategies for modulating melanin levels have been developed by the pharmaceutical and cosmetic industries. We reported previously that voglibose, which is a well-known anti-hyperglycemic agent, could be used as an anti-melanogenic agent by inhibiting α-glucosidase activity and reducing tyrosinase protein levels. Of the other representative anti-hyperglycemic agents, acarbose showed less anti-melanogenic activity despite its potent anti-hyperglycemic efficacy. In this study, we report that acarbose exhibited considerable anti-melanogenic activity when melanocytes were co-treated with acarbose and a digestible sugar, such as maltose. Simultaneous treatment with maltose augmented the inhibitory effect of acarbose on α-glucosidase activity by enhancing its stability under physiological conditions, leading to the down-regulation of tyrosinase. These results suggest that the co-treatment of anti-hyperglycemic agents with hydrolysable sugars may be a useful tool for reducing glucosidase-associated melanogenesis as a potent sugar-based anti-melanogenic regimen.

Protectin DX, a double lipoxygenase product of DHA, inhibits both ROS production in human neutrophils and cyclooxygenase activities

PubMed Central

Liu, Miao; Boussetta, Tarek; Makni-Maalej, Karama; Fay, Michèle; Driss, Fathi; El-Benna, Jamel; Lagarde, Michel; Guichardant, Michel

2014-01-01

Neutrophils play a major role in inflammation by releasing large amounts of reactive oxygen species (ROS) produced by NADPH oxidase (NOX) and myeloperoxidase (MPO). This ROS overproduction is mediated by phosphorylation of the NOX subunits with an uncontrolled manner. Therefore, targeting neutrophil subunits would represent a promising strategy to moderate NOX activity, lower ROS, and other inflammatory agents, such as cytokines and leukotrienes, produced by neutrophils. For this purpose, we investigated the effects of protectin DX (PDX) - a docosahexaenoic acid (DHA) di-hydroxylated product which inhibits blood platelet aggregation - on neutrophil activation in vitro. We found that PDX decreases ROS production, inhibits NOX activation and MPO release from neutrophils. We also confirm, that PDX is an anti-aggregatory and anti-inflammatory agent by inhibiting both cyclooxygenase-1 and -2 (COX-1 and COX-2, E.C. 1.14.99.1) as well as COX-2 in lipopolysaccharides (LPS)-treated human neutrophils. However, PDX has no effect on the 5-lipoxygenase pathway that produces the chemotactic agent leukotriene B4 (LTB4). Taken together, our results suggest that PDX could be a protective agent against neutrophil invasion in chronic inflammatory diseases. PMID:24254970

Patient care in a biological safety level-4 (BSL-4) environment.

PubMed

Marklund, LeRoy A

2003-06-01

The greatest threats to America's public health include accidental importation of deadly diseases by international travelers and the release of biologic weapons by our adversaries. The greatest failure is unpreparedness because international travel and dispersion of biologic agents by our enemies are inevitable. An effective medical defense program is the recommended deterrent against these threats. The United States has a federal response plan in place that includes patient care and patient transport by using the highest level of biologic containment: BSL-4. The DoD has the capability to provide intensive care for victims infected with highly infectious yet unknown biologic agents in an environment that protects the caregiver while allowing scientists to study the characteristics of these new agents and assess the effectiveness of treatment. Army critical care nurses are vital in the biologic medical defense against unidentified infectious diseases, accidental occupational exposures, or intentional dispersion of weaponized biologic agents. Research that carefully advances healthcare using BSL-4 technology addresses the challenges of the human element of BSL-4 containment patient care, and BSL-4 patient transport enhances our nation's ability to address the emerging biologic threats we confront in the future.

Protective effect of the edible brown alga Ecklonia stolonifera on doxorubicin-induced hepatotoxicity in primary rat hepatocytes.

PubMed

Jung, Hyun Ah; Kim, Jae-I; Choung, Se Young; Choi, Jae Sue

2014-08-01

As part of our efforts to isolate anti-hepatotoxic agents from marine natural products, we screened the ability of 14 edible varieties of Korean seaweed to protect against doxorubicin-induced hepatotoxicity in primary rat hepatocytes. Among the crude extracts of two Chlorophyta (Codium fragile and Capsosiphon fulvescens), seven Phaeophyta (Undaria pinnatifida, Sargassum thunbergii, Pelvetia siliquosa, Ishige okamurae, Ecklonia cava, Ecklonia stolonifera and Eisenia bicyclis), five Rhodophyta (Chondrus ocellatus, Gelidium amansii, Gracilaria verrucosa, Symphycladia latiuscula and Porphyra tenera), and the extracts of Ecklonia stolonifera, Ecklonia cava, Eisenia bicyclis and Pelvetia siliquosa exhibited significant protective effects on doxorubicin-induced hepatotoxicity, with half maximal effective concentration (EC50) values of 2.0, 2.5, 3.0 and 15.0 μg/ml, respectively. Since Ecklonia stolonifera exhibits a significant protective potential and is frequently used as foodstuff, we isolated six phlorotannins, including phloroglucinol (1), dioxinodehydroeckol (2), eckol (3), phlorofucofuroeckol A (4), dieckol (5) and triphloroethol-A (6). Phlorotannins 2 ∼ 6 exhibited potential protective effects on doxorubicin-induced hepatotoxicity, with corresponding EC50 values of 3.4, 8.3, 4.4, 5.5 and 11.5 μg/ml, respectively. The results clearly demonstrated that the anti-hepatotoxic effects of Ecklonia stolonifera and its isolated phlorotannins are useful for further exploration and development of therapeutic modalities for treatment of hepatotoxicity. © 2014 Royal Pharmaceutical Society.

GENO PROTECTIVE AND ANTI-APOPTOTIC EFFECT OF GREEN TEA AGAINST PERINATAL LIPOPOLYSACCHARIDE-EXPOSURE INDUCED LIVER TOXICITY IN RAT NEWBORNS

PubMed Central

Allam, Ahmed A.; Gabr, Sami A.; Ajarem, Jamaan; Alghadir, Ahmad H.; Sekar, Revathi; Chow, Billy KC

2017-01-01

Background: This study aims to examine the protective effect of green tea on the disturbances in oxidative stress and apoptosis related factors, mostly produced due to perinatal lipopolysaccharide (LPS) exposure, that subsequently induces liver cell damage. Materials and Methods: Anti-free radical, Antioxidant, scavenging, geno-protective, and antiapoptotic activity of aqueous green tea extract (AGTE) were assessed against LPS-induced hepatic dysfunction in newborn-rats. AGTE at doses of 100 & 200 mg/kg was orally administered daily to rat dams, during gestation and lactation. Results: AGTE was observed to exhibit protective effects by significantly attenuating LPS-induced alterations in serum AST, ALT, bilirubin, and albumin levels. Significant increase in the total antioxidant capacity (TAC), DNA contents, and reduction in nitric oxide (NO) levels were observed in AGTE treated rats comparing LPS-toxicated ones. Additionally, AGTE treatment significantly down-regulated apoptotic markers and this effect was directly correlated to the degree of hepatic fibrosis. The possible mechanisms of the potential therapeutic-liver protective effect of AGTE could be due to free radical scavenging potential and antiapoptotic properties caused by the presence of antioxidant polyphenolic components in AGTE. Conclusion: We thereby propose, based on our findings, that the anti-free radical and anti-apoptotic inducing properties of AGTE active constituents attribute to its functional efficacy as anti-fibrotic agent. PMID:28573233

Ethylhexylglycerin Impairs Membrane Integrity and Enhances the Lethal Effect of Phenoxyethanol

PubMed Central

Langsrud, Solveig; Steinhauer, Katrin; Lüthje, Sonja; Weber, Klaus; Goroncy-Bermes, Peter; Holck, Askild L.

2016-01-01

Preservatives are added to cosmetics to protect the consumers from infections and prevent product spoilage. The concentration of preservatives should be kept as low as possible and this can be achieved by adding potentiating agents. The aim of the study was to investigate the mechanisms behind potentiation of the bactericidal effect of a commonly used preservative, 2-phenoxyethanol (PE), by the potentiating agent ethylhexylglycerin (EHG). Sub-lethal concentrations of EHG (0.075%) and PE (0.675%) in combination led to rapid killing of E. coli (> 5 log reduction of cfu after 30 min), leakage of cellular constituents, disruption of the energy metabolism, morphological deformities of cells and condensation of DNA. Used alone, EHG disrupted the membrane integrity even at low concentrations. In conclusion, sub-lethal concentrations of EHG potentiate the effect of PE through damage of the cell membrane integrity. Thus, adding EHG to PE in a 1:9 ratio has a similar effect on membrane damage and bacterial viability as doubling the concentration of PE. This study provides insight about the mechanism of action of a strong potentiating agent, EHG, which is commonly used in cosmetics together with PE. PMID:27783695

Development, registration and commercialization of microbial pesticides for plant protection.

PubMed

Montesinos, Emilio

2003-12-01

Plant protection against pathogens, pests and weeds has been progressively reoriented from a therapeutic approach to a rational use of pesticide chemicals in which consumer health and environmental preservation prevail over any other productive or economic considerations. Microbial pesticides are being introduced in this new scenario of crop protection and currently several beneficial microorganisms are the active ingredients of a new generation of microbial pesticides or the basis for many natural products of microbial origin. The development of a microbial pesticide requires several steps addressed to its isolation in pure culture and screening by means of efficacy bioassays performed in vitro, ex vivo, in vivo, or in pilot trials under real conditions of application (field, greenhouse, post-harvest). For the commercial delivery of a microbial pesticide, the biocontrol agent must be produced at an industrial scale (fermentation), preserved for storage and formulated by means of biocompatible additives to increase survival and to improve the application and stability of the final product. Despite the relative high number of patents for biopesticides, only a few of them have materialized in a register for agricultural use. The excessive specificity in most cases and biosafety or environmental concerns in others are major limiting factors. Non-target effects may be possible in particular cases, such as displacement of beneficial microorganisms, allergenicity, toxinogencity (production of secondary metabolites toxic to plants, animals, or humans), pathogenicity (to plants or animals) by the agent itself or due to contaminants, or horizontal gene transfer of these characteristics to non-target microorganisms. However, these non-target effects should not be evaluated in an absolute manner, but relative to chemical control or the absence of any control of the target disease (for example, toxins derived from the pathogen). Consumer concerns about live microbes due to emerging food-borne diseases and bioterrorism do not help to create a socially receptive environment to microbial pesticides. The future of microbial pesticides is not only in developing new active ingredients based on microorganisms beneficial to plants, but in producing self-protected plants (so-called plant-incorporated pesticides) by transforming agronomically high-value crop plants with genes from biological control agents.

Tafenoquine: a promising new antimalarial agent.

PubMed

Crockett, Maryanne; Kain, Kevin C

2007-05-01

Malaria remains an important cause of global morbidity and mortality. As antimalarial drug resistance escalates, new safe and effective medications are necessary to prevent and treat malarial infection. Tafenoquine is an 8-aminoquinoline antimalarial that is presently under development. It has a long half-life of approximately 14 days and is generally safe and well tolerated, although it cannot be used in pregnant women and individuals who are deficient in the enzyme glucose-6-phosphate dehydrogenase. In well-designed studies, tafenoquine was highly effective in both the radical cure of relapsing malaria and causal prophylaxis of Plasmodium vivax and P. falciparum infections with protective efficacies of > or = 90%. Given its causal activity and safety profile, tafenoquine represents a potentially exciting alternative to standard agents for the prevention and radical cure of malaria.

Epigallocatechin-3-gallate, a prototypic chemopreventative agent for protection against cisplatin-based ototoxicity

PubMed Central

Borse, Vikrant; Al Aameri, Raheem F H; Sheehan, Kelly; Sheth, Sandeep; Kaur, Tejbeer; Mukherjea, Debashree; Tupal, Srinivasan; Lowy, Michelle; Ghosh, Sumana; Dhukhwa, Asmita; Bhatta, Puspanjali; Rybak, Leonard P; Ramkumar, Vickram

2017-01-01

Cisplatin-induced ototoxicity is one of the major factors limiting cisplatin chemotherapy. Ototoxicity results from damage to outer hair cells (OHCs) and other regions of the cochlea. At the cellular level, cisplatin increases reactive oxygen species (ROS) leading to cochlear inflammation and apoptosis. Thus, ideal otoprotective drugs should target oxidative stress and inflammatory mechanisms without interfering with cisplatin's chemotherapeutic efficacy. In this study, we show that epigallocatechin-3-gallate (EGCG) is a prototypic agent exhibiting these properties of an effect otoprotective agent. Rats administered oral EGCG demonstrate reduced cisplatin-induced hearing loss, reduced loss of OHCs in the basal region of the cochlea and reduced oxidative stress and apoptotic markers. EGCG also protected against the loss of ribbon synapses associated with inner hair cells and Na+/K+ ATPase α1 in the stria vascularis and spiral ligament. In vitro studies showed that EGCG reduced cisplatin-induced ROS generation and ERK1/2 and signal transducer and activator of transcription-1 (STAT1) activity, but preserved the activity of STAT3 and Bcl-xL. The increase in STAT3/STAT1 ratio appears critical for mediating its otoprotection. EGCG did not alter cisplatin-induced apoptosis of human-derived cancer cells or cisplatin antitumor efficacy in a xenograft tumor model in mice because of its inability to rescue the downregulation of STAT3 in these cells. These data suggest that EGCG is an ideal otoprotective agent for treating cisplatin-induced hearing loss without compromising its antitumor efficacy. PMID:28703809

Exposure of U.S. National Parks to land use and climate change 1900-2100.

PubMed

Hansen, Andrew J; Piekielek, Nathan; Davis, Cory; Haas, Jessica; Theobald, David M; Gross, John E; Monahan, William B; Olliff, Tom; Running, Steven W

2014-04-01

Many protected areas may not be adequately safeguarding biodiversity from human activities on surrounding lands and global change. The magnitude of such change agents and the sensitivity of ecosystems to these agents vary among protected areas. Thus, there is a need to assess vulnerability across networks of protected areas to determine those most at risk and to lay the basis for developing effective adaptation strategies. We conducted an assessment of exposure of U.S. National Parks to climate and land use change and consequences for vegetation communities. We first defined park protected-area centered ecosystems (PACEs) based on ecological principles. We then drew on existing land use, invasive species, climate, and biome data sets and models to quantify exposure of PACEs from 1900 through 2100. Most PACEs experienced substantial change over the 20th century (> 740% average increase in housing density since 1940, 13% of vascular plants are presently nonnative, temperature increase of 1 degree C/100 yr since 1895 in 80% of PACEs), and projections suggest that many of these trends will continue at similar or increasingly greater rates (255% increase in housing density by 2100, temperature increase of 2.5 degrees-4.5 degrees C/100 yr, 30% of PACE areas may lose their current biomes by 2030). In the coming century, housing densities are projected to increase in PACEs at about 82% of the rate of since 1940. The rate of climate warming in the coming century is projected to be 2.5-5.8 times higher than that measured in the past century. Underlying these averages, exposure of individual park PACEs to change agents differ in important ways. For example, parks such as Great Smoky Mountains exhibit high land use and low climate exposure, others such as Great Sand Dunes exhibit low land use and high climate exposure, and a few such as Point Reyes exhibit high exposure on both axes. The cumulative and synergistic effects of such changes in land use, invasives, and climate are expected to dramatically impact ecosystem function and biodiversity in national parks. These results are foundational to developing effective adaptation strategies and suggest policies to better safeguard parks under broad-scale environmental change.

Protective effect of Clerodendron glandulosum extract against experimentally induced metabolic syndrome in rats.

PubMed

Jadeja, Ravirajsinh N; Thounaojam, Menaka C; Ansarullah; Patel, Vaibhav B; Devkar, Ranjitsinh V; Ramachandran, A V

2010-12-01

Metabolic syndrome (MetS) has become one of the major health burdens worldwide. To date, no single pharmacological agent has been developed to correct metabolic abnormalities associated with MetS. Use of indigenous medicinal plants as alternative medicines against MetS could be beneficial due to multiple therapeutic usage, easy availability, and relatively few side effects. To investigate the protective effect of Clerodendron glandulosum Coleb. (Verbenaceae) aqueous leaf extract (CgE) against experimentally induced MetS in rats. Changes in body weight, food and fluid intake, plasma glucose, insulin, fasting insulin resistance index (FIRI), plasma total lipid profile, free fatty acids (FFA), oral glucose tolerance test (OGTT), blood pressure and vascular reactivity have been investigated in various experimental groups. Fructose+CgE groups recorded significant decrement (P <0.05) in plasma glucose, insulin, FIRI, total cholesterol, triglycerides, LDL, VLDL and FFA, whereas plasma HDL level was significantly increased (P <0.05) along with an efficient clearance of glucose during OGTT and lowered area under curve values. FRU+CgE groups also showed significantly decreased (P <0.05) mean arterial blood pressure along with decreased vasoconstriction and increased vasorelaxation in response to administration of various pharmacological agents. These results were comparable with metformin treated rats. C. glandulosum leaf extract ameliorates experimentally induced MetS by improving dyslipidemia and insulin resistance. This study provides the first pharmacological evidence for the protective role of C. glandulosum leaves against experimentally induced MetS. Thus, therapeutic use of C. glandulosum in controlling MetS is indicated.

Protocatechuic Aldehyde Attenuates Cisplatin-Induced Acute Kidney Injury by Suppressing Nox-Mediated Oxidative Stress and Renal Inflammation

PubMed Central

Gao, Li; Wu, Wei-Feng; Dong, Lei; Ren, Gui-Ling; Li, Hai-Di; Yang, Qin; Li, Xiao-Feng; Xu, Tao; Li, Zeng; Wu, Bao-Ming; Ma, Tao-Tao; Huang, Cheng; Huang, Yan; Zhang, Lei; Lv, Xiongwen; Li, Jun; Meng, Xiao-Ming

2016-01-01

Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress, and programmed cell death of renal tubular epithelial cells, all of which lead to high mortality rates in patients. In this study, we examined the protective effect of protocatechuic aldehyde (PA) in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza (Lamiaceae). Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA blocks cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients receiving cisplatin treatment. PMID:27999546

Effect of enrofloxacin on Haemophilus parasuis infection, disease and immune response.

PubMed

Macedo, Nubia; Cheeran, Maxim C J; Rovira, Albert; Holtcamp, Andrew; Torremorell, Montserrat

2017-02-01

Haemophilus parasuis, the causative agent of Glasser's disease, is a pathogen that colonizes the upper respiratory tract (URT) of pigs, invades the bloodstream and causes polyserositis. Because antimicrobials are highly effective against H. parasuis, we hypothesized that they could have a detrimental effect on the establishment of an immune response if given at the time of URT colonization. In this study, we characterized clinical outcomes and antibody and IFN-γ responses to H. parasuis in pigs treated with enrofloxacin before or after low dose inoculation with a pathogenic H. parasuis strain. Pigs that were only inoculated with the agent (EXP group) and pigs that were treated with enrofloxacin and then inoculated (ABT/EXP group) developed signs of disease starting at 4days post inoculation (DPI), presented a significant increase in serum IgG and were protected against a subsequent homologous challenge. In contrast, pigs treated with antibiotic after inoculation (EXP/ABT group) neither showed signs of disease nor seroconverted (IgG) after low dose inoculation. EXP/ABT pigs as well as naïve control pigs [enrofloxacin only (ABT) and challenge only (CHA)] were susceptible to challenge. Variable levels of antibodies in bronchioalveolar fluid and IFN-γ in peripheral blood mononuclear cells were observed after H. parasuis inoculation, but were not associated with protection. In summary, only pigs treated before low dose H. parasuis inoculation seroconverted and were protected against subsequent challenge. Results from this study can help determine timing of antimicrobial use and contribute to our current understanding of judicious antibiotic use. Copyright © 2016 Elsevier B.V. All rights reserved.

Effectiveness of permethrin plus-C (Masterline®) and carbaryl (Sevin SL®) for protecting individual, high-value pines from bark beetle attack

Treesearch

Christopher J. Fettig; Thomas E. DeGomez; Kenneth E. Gibson; Christopher J. Dabney; Robert R. Borys

2006-01-01

Bark beetles (Coleoptera: Scolytidae) are commonly recognized as the most important mortality agent in western coniferous forests. High value trees, such as those located in residential, recreational, or administrative sites, are particularly susceptible to attack. Regardless of landowner objectives, tree losses in these unique environments generally have a...

Chemotherapy-induced bystander effect in response to several chloroethylnitrosoureas: an origin independent of DNA damage?

PubMed

Merle, Patrick; Morvan, Daniel; Caillaud, Denis; Demidem, Aicha

2008-01-01

Chloroethylnitrosourea (CENU) chemotherapy is used for the treatment of melanoma tumors. The main mechanism of action of this anticancer agent is via DNA damage. We recently showed in murine experiments using a parental double B16 melanoma tumor model that, after treatment of primary tumors with cystemustine (CENU agent), untreated secondary tumors exhibited growth inhibition and metabolism disorders. The response of secondary untreated tumor was called the chemotherapy-induced bystander effect. To see whether chemotherapy-induced bystander effects were induced with other members of the CENU family, we compared three CENU(s) used in melanoma treatment: cystemustine, carmustine and fotemustine. Our results demonstrate that fotemustine, like cystemustine, but not carmustine induced a protective effect against secondary untreated tumors including alterations in phospholipid derivative and glutathione which are the metabolic signature of the bystander effect. From these data we may conclude that DNA damage to the primary tumor is not sufficient to explain chemotherapy-induced bystander effects.

Geraniol-a flavoring agent with multifunctional effects in protecting the gastric and duodenal mucosa.

PubMed

de Carvalho, Katharinne Ingrid Moraes; Bonamin, Flavia; Dos Santos, Raquel Cássia; Périco, Larissa Lucena; Beserra, Fernando Pereira; de Sousa, Damião Pergentino; Filho, José Maria Barbosa; da Rocha, Lucia Regina Machado; Hiruma-Lima, Clelia Akiko

2014-04-01

Geraniol is an acyclic monoterpene alcohol commonly used as a flavoring agent. The present study was undertaken to investigate antiulcerogenic effects of geraniol and to determine the possible mechanisms involved in this action. In the model of the ethanol-induced ulcer, treatment of rats with geraniol by oral route significantly inhibited gastric lesions by 70 % (7.50 mg/kg) to 99 % (200 mg/kg). Analysis of the gastric tissue of rats treated with geraniol (7.50 mg/kg) revealed that total glutathione content levels (GSH) increased and levels of myeloperoxidase (MPO) decreased in the gastric mucosa. Oral treatment with geraniol significantly decreased the number of ulcerative lesions induced by ischemia/reperfusion injury by 71 % and the duodenal ulcers induced by cysteamine by 68 %. The action of geraniol was mediated by the activation of defensive mucosa-protective factors such as the nitric oxide (NO) pathway, endogenous prostaglandins, increased mucus production, increased sulfhydryl compounds, antioxidant properties and the stimulation of calcitonin gene-related peptide (CGRP) release through the activation of transient receptor potential vanilloid (TRPV). The multifaceted gastroprotective mechanisms of geraniol represent a promising option for the treatment of gastric and duodenal mucosa injury.

Quercetin topical application, from conventional dosage forms to nanodosage forms.

PubMed

Hatahet, T; Morille, M; Hommoss, A; Devoisselle, J M; Müller, R H; Bégu, S

2016-11-01

Skin is a multifunctional organ with activities in protection, metabolism and regulation. Skin is in a continuous exposure to oxidizing agents and inflammogens from the sun and from the contact with the environment. These agents may overload the skin auto-defense capacity. To strengthen skin defense mechanisms against oxidation and inflammation, supplementation of exogenous antioxidants is a promising strategy. Quercetin is a flavonoid with very pronounced effective antioxidant and antiinflammatory activities, and thus a candidate of first choice for such skin supplementation. Quercetin showed interesting actions in cellular and animal based models, ranging from protecting cells from UV irradiation to support skin regeneration in wound healing. However, due to its poor solubility, quercetin has limited skin penetration ability, and various formulation approaches were taken to increase its dermal penetration. In this article, the quercetin antioxidant and antiinflammatory activities in wound healing and supporting skin against aging are discussed in detail. In addition, quercetin topical formulations from conventional emulsions to novel nanoformulations in terms of skin penetration enhancement are also presented. This article gives a comprehensive review of quercetin for topical application from biological effects to pharmaceutical formulation design for the last 25 years of research. Copyright © 2016 Elsevier B.V. All rights reserved.

[A Study on Quantitative Evaluation of Damage in Conservation of Ceramics from Huaguangjiao I Shipwreck with ICP-AES].

PubMed

Li, Wen-jing; Chen, Yue; Li, Nai-sheng; Li, Bin; Luo, Wu-gan

2015-03-01

ICP-AES was used to determine the elemental composition of solutions in different conservation steps for understanding the impact of cleaning agents on ceramics from Huaguangjiao I shipwreck. The results showed that high content in solution of Al, Fe, Mg ions, which can be indexes to reflect the damage in conservation of ceramics. According to these indexes, we discovered that agents of strong cleaning ability bring more damage to ceramic samples. Meanwhile, the state of preservation of the ceramics was closely related to the damage in conservation. Ceramics in an excellent state of preservation endure less damage than that in bad state. We also found that each cleaning agent cause certain degree of damage on porcelains, even neutral reagent, like deionized water. Moreover, moderate cleaning reagent, when using a long time, bring the same degree of damage as the strong acid. Therefore, in actual protection procedure, for conservation ceramics safe and effective, damage of each cleaning agents and cumulative damage should be considered.

Essential oils and their principal constituents as antimicrobial agents for synthetic packaging films.

PubMed

Kuorwel, Kuorwel K; Cran, Marlene J; Sonneveld, Kees; Miltz, Joseph; Bigger, Stephen W

2011-01-01

Spices and herbal plant species have been recognized to possess a broad spectrum of active constituents that exhibit antimicrobial (AM) activity. These active compounds are produced as secondary metabolites associated with the volatile essential oil (EO) fraction of these plants. A wide range of AM agents derived from EOs have the potential to be used in AM packaging systems which is one of the promising forms of active packaging systems aimed at protecting food products from microbial contamination. Many studies have evaluated the AM activity of synthetic AM and/or natural AM agents incorporated into packaging materials and have demonstrated effective AM activity by controlling the growth of microorganisms. This review examines the more common synthetic and natural AM agents incorporated into or coated onto synthetic packaging films for AM packaging applications. The focus is on the widely studied herb varieties including basil, oregano, and thyme and their EOs. © 2011 Institute of Food Technologists®

By improving regional cortical blood flow, attenuating mitochondrial dysfunction and sequential apoptosis galangin acts as a potential neuroprotective agent after acute ischemic stroke.

PubMed

Li, Shaojing; Wu, Chuanhong; Zhu, Li; Gao, Jian; Fang, Jing; Li, Defeng; Fu, Meihong; Liang, Rixin; Wang, Lan; Cheng, Ming; Yang, Hongjun

2012-11-09

Ischemic stroke is a devastating disease with a complex pathophysiology. Galangin is a natural flavonoid isolated from the rhizome of Alpina officinarum Hance, which has been widely used as an antioxidant agent. However, its effects against ischemic stroke have not been reported and its related neuroprotective mechanism has not really been explored. In this study, neurological behavior, cerebral infarct volumes and the improvement of the regional cortical blood flow (rCBF) were used to evaluate the therapeutic effect of galangin in rats impaired by middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia. Furthermore, the determination of mitochondrial function and Western blot of apoptosis-related proteins were performed to interpret the neuroprotective mechanism of galangin. The results showed that galangin alleviated the neurologic impairments, reduced cerebral infarct at 24 h after MCAO and exerted a protective effect on the mitochondria with decreased production of mitochondrial reactive oxygen species (ROS). These effects were consistent with improvements in the membrane potential level (Dym), membrane fluidity, and degree of mitochondrial swelling in a dose-dependent manner. Moreover, galangin significantly improved the reduced rCBF after MCAO. Western blot analysis revealed that galangin also inhibited apoptosis in a dose-dependent manner concomitant with the up-regulation of Bcl-2 expression, down-regulation of Bax expression and the Bax/Bcl-2 ratio, a reduction in cytochrome c release from the mitochondria to the cytosol, the reduced expression of activated caspase-3 and the cleavage of poly(ADP-ribose) polymerase (PARP). All these data in this study demonstrated that galangin might have therapeutic potential for ischemic stroke and play its protective role through the improvement in rCBF, mitochondrial protection and inhibiting caspase-dependent mitochondrial cell death pathway for the first time.

Antiulcerogenic effects of coconut (Cocos nucifera) extract in rats.

PubMed

Nneli, R O; Woyike, O A

2008-07-01

A warm water crude extract of coconut milk and a coconut water dispersion were investigated for their antiulcerogenic effects in male Wistar albino rats. Ulcers were induced in the male rats by subcutaneous administration of indomethacin (40 mg/kg) using standard procedures. The ulcer inhibition rate (UIR) was taken as a measure of the cytoprotection offered by test substances. Coconut milk (2 mL daily oral feeding) produced a stronger percentage (54%) reduction in the mean ulcer area than coconut water (39%). The effect of coconut milk was similar to the effect of sucralfate that reduced the mean ulcer area by 56% in this study. Sucralfate is a conventional cytoprotective agent. The results showed that coconut milk and water via macroscopic observation had protective effects on the ulcerated gastric mucosa. It is concluded that coconut milk offered stronger protection on indomethacin-induced ulceration than coconut water in rats.

Extending self-organizing particle systems to problem solving.

PubMed

Rodríguez, Alejandro; Reggia, James A

2004-01-01

Self-organizing particle systems consist of numerous autonomous, purely reflexive agents ("particles") whose collective movements through space are determined primarily by local influences they exert upon one another. Inspired by biological phenomena (bird flocking, fish schooling, etc.), particle systems have been used not only for biological modeling, but also increasingly for applications requiring the simulation of collective movements such as computer-generated animation. In this research, we take some first steps in extending particle systems so that they not only move collectively, but also solve simple problems. This is done by giving the individual particles (agents) a rudimentary intelligence in the form of a very limited memory and a top-down, goal-directed control mechanism that, triggered by appropriate conditions, switches them between different behavioral states and thus different movement dynamics. Such enhanced particle systems are shown to be able to function effectively in performing simulated search-and-collect tasks. Further, computational experiments show that collectively moving agent teams are more effective than similar but independently moving ones in carrying out such tasks, and that agent teams of either type that split off members of the collective to protect previously acquired resources are most effective. This work shows that the reflexive agents of contemporary particle systems can readily be extended to support goal-directed problem solving while retaining their collective movement behaviors. These results may prove useful not only for future modeling of animal behavior, but also in computer animation, coordinated movement control in robotic teams, particle swarm optimization, and computer games.

Effect of sulphur mustard on human skin cell lines with differential agent sensitivity.

PubMed

Simpson, Rachel; Lindsay, Christopher D

2005-01-01

The ability of sulphur mustard (HD) to induce DNA damage places limits on the efficacy of approaches aimed at protecting human cells from the cytotoxic effects of HD using a variety of protective agents such as thiol-containing esters and protease inhibitors. In the present study, potential alternative strategies were investigated by examining the differential effects of HD on G361, SVK14, HaCaT and NCTC 2544 human skin cells. The G361 cell line was more resistant to the cytotoxic effects of HD than the NCTC, HaCaT and SVK14 cell lines at HD doses of >3 and <100 microM HD as determined by the MTT assay. At 72 h after exposure to 60 microM HD there was up to an 8.8-fold difference (P < 0.0001) between G361 and SVK14 cell culture viability. Buthionine sulphoximine (BSO) pretreatment increased the sensitivity of all four cell lines to HD. A substantial proportion of the resistance of G361 cells to HD was attributable to BSO-mediated effects on antioxidant-mediated metabolism, although G361 cultures still retained a high degree of viability at 30 microM HD following BSO pretreatment. Cell cycle analysis confirmed that SVK14 cells were relatively more sensitive to HD, as shown by the 2.1-fold reduction (P < 0.0001) in the percentage of cells in G0/G1 phase 24 h after HD exposure compared with control cultures. This compared well with a 1.2-fold increase (P < 0.05) in the percentage of G361 cells in G0/G1 phase following HD exposure, suggesting the existence of a more efficient G0/G1 checkpoint control mechanism in this cell line. Manipulation of the cell cycle using various modulating agents did not increase the resistance of cell lines to the cytotoxic effects of HD. Crown copyright 2005

EFFECT OF GAMMA IRRADIATION AND AET ON RAT BLOOD CHOLINESTERASE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, M.W.; Baker, R.D.; Covill, R.W.

1961-03-01

Whole-body gamma irradiation in the rat produced significant whole-blood cholinesterase depression on the tenth day at a dosage level of 75 r. The levels tested when plotted and extrapolared indicated threshold changes in cholinesterase activity would be in the vicinity of 20 to 30 r. AET alone, while producing some mild cholinesterase depression, failed to protect whole-blood cholinesterase activity from the effects of gamma irradiation at the levels of agent and irradiation tested. (auth)

Protective effects of papaverine salicylate in mouse ear dermatitis and PAF-induced rat paw oedema.

PubMed

de Bernardis, E; Leonardi, G; Caruso, A; Cutuli, V M; Amico-Roxas, M

1994-08-01

Papaverine salicylate (MR-800) has been tested as a topical antiinflammatory agent in several models of skin inflammation in rodents, such as mouse ear dermatitis induced by croton oil, cantharidin or zymosan, and rat paw oedema induced by PAF. MR-800 exerted a dose-dependent inhibitory activity in all assays, when equimolar doses of sodium salicylate or papaverine were less effective, suggesting the existence of a favourable synergism between salicylate and papaverine.

Are biological control agents, isolated from tropical fruits, harmless to potential consumers?

PubMed

Ocampo-Suarez, Iris Betsabee; López, Zaira; Calderón-Santoyo, Montserrat; Ragazzo-Sánchez, Juan Arturo; Knauth, Peter

2017-11-01

Postharvest losses of fruits and vegetables can reach up to 25% in developed and up to 50% in developing countries. (Sub)tropical fruits are especially susceptible because their protecting peel can easily be damaged. Traditionally used pesticides are associated to environmental pollution and possible harmful health effects. An alternative are biocontrol agents (BCA), means bacteria or yeasts applied onto the fruits to inhibit the growth of phytopathogens. Many reports on their effectiveness have been published, however, reports on their harmlessness to consumers are still rare. Culture extracts of six BCAs, tested on two human lines (Caco-2, HeLa), exhibited no cytotoxic effect, when used directly (1×) to protect the fruits; however, when they are 5×overconcentrated, the confluence of proliferating cells was reduced, but not of differentiated Caco-2. In both cases necrosis was not increased. On proliferating cells, the 5×-extract from Cryptococcus laurentii or Debaryomyces hansenii reduced lysosome functionality and the 6.25×extract from Meyerozyma guilliermondii or Candida famata increased membrane permeability, while only the 25×-extract from M. guilliermondii or M. caribbica reduced slightly the metabolic activity. The extract of Bacillus subtilis showed no cytotoxic effect up to 10× concentration. Overall, their low cytotoxicity combined with high biodegradability make these products suitable for sustainable agriculture. Copyright © 2017 Elsevier Ltd. All rights reserved.

Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms.

PubMed

Nichols, Joi A; Katiyar, Santosh K

2010-03-01

Epidemiological, clinical and laboratory studies have implicated solar ultraviolet (UV) radiation in various skin diseases including, premature aging of the skin and melanoma and non-melanoma skin cancers. Chronic UV radiation exposure-induced skin diseases or skin disorders are caused by the excessive induction of inflammation, oxidative stress and DNA damage, etc. The use of chemopreventive agents, such as plant polyphenols, to inhibit these events in UV-exposed skin is gaining attention. Chemoprevention refers to the use of agents that can inhibit, reverse or retard the process of these harmful events in the UV-exposed skin. A wide variety of polyphenols or phytochemicals, most of which are dietary supplements, have been reported to possess substantial skin photoprotective effects. This review article summarizes the photoprotective effects of some selected polyphenols, such as green tea polyphenols, grape seed proanthocyanidins, resveratrol, silymarin and genistein, on UV-induced skin inflammation, oxidative stress and DNA damage, etc., with a focus on mechanisms underlying the photoprotective effects of these polyphenols. The laboratory studies conducted in animal models suggest that these polyphenols have the ability to protect the skin from the adverse effects of UV radiation, including the risk of skin cancers. It is suggested that polyphenols may favorably supplement sunscreens protection, and may be useful for skin diseases associated with solar UV radiation-induced inflammation, oxidative stress and DNA damage.

Emerging Infections of CNS: Avian Influenza A Virus, Rift Valley Fever Virus and Human Parechovirus.

PubMed

Wiley, Clayton A; Bhardwaj, Nitin; Ross, Ted M; Bissel, Stephanie J

2015-09-01

History is replete with emergent pandemic infections that have decimated the human population. Given the shear mass of humans that now crowd the earth, there is every reason to suspect history will repeat itself. We describe three RNA viruses that have recently emerged in the human population to mediate severe neurological disease. These new diseases are results of new mutations in the infectious agents or new exposure pathways to the agents or both. To appreciate their pathogenesis, we summarize the essential virology and immune response to each agent. Infection is described in the context of known host defenses. Once the viruses evade immune defenses and enter central nervous system (CNS) cells, they rapidly co-opt host RNA processing to a cataclysmic extent. It is not clear why the brain is particularly susceptible to RNA viruses; but perhaps because of its tremendous dependence on RNA processing for physiological functioning, classical mechanisms of host defense (eg, interferon disruption of viral replication) are diminished or not available. Effectiveness of immunity, immunization and pharmacological therapies is reviewed to contextualize the scope of the public health challenge. Unfortunately, vaccines that confer protection from systemic disease do not necessarily confer protection for the brain after exposure through unconventional routes. © 2015 International Society of Neuropathology.

Suppressing iron oxide nanoparticle toxicity by vascular targeted antioxidant polymer nanoparticles.

PubMed

Cochran, David B; Wattamwar, Paritosh P; Wydra, Robert; Hilt, J Zach; Anderson, Kimberly W; Eitel, Richard E; Dziubla, Thomas D

2013-12-01

The biomedical use of superparamagnetic iron oxide nanoparticles has been of continued interest in the literature and clinic. Their ability to be used as contrast agents for imaging and/or responsive agents for remote actuation makes them exciting materials for a wide range of clinical applications. Recently, however, concern has arisen regarding the potential health effects of these particles. Iron oxide toxicity has been demonstrated in in vivo and in vitro models, with oxidative stress being implicated as playing a key role in this pathology. One of the key cell types implicated in this injury is the vascular endothelial cells. Here, we report on the development of a targeted polymeric antioxidant, poly(trolox ester), nanoparticle that can suppress oxidative damage. As the polymer undergoes enzymatic hydrolysis, active trolox is locally released, providing a long term protection against pro-oxidant agents. In this work, poly(trolox) nanoparticles are targeted to platelet endothelial cell adhesion molecules (PECAM-1), which are able to bind to and internalize in endothelial cells and provide localized protection against the cytotoxicity caused by iron oxide nanoparticles. These results indicate the potential of using poly(trolox ester) as a means of mitigating iron oxide toxicity, potentially expanding the clinical use and relevance of these exciting systems. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of Inhibitor Agents Addition on Corrosion Resistance Performance of Titania Sol-Gel Coatings Applied on 304 Stainless Steel

NASA Astrophysics Data System (ADS)

Shanaghi, Ali; Chu, Paul K.; Moradi, Hadi

Hybrid organic-inorganic coatings are deposited on 304 stainless steel substrates by the sol-gel technique to improve the corrosion resistance. A titania-based nanostructured hybrid sol-gel coating is impregnated with three different microencapsulated healing agents (inhibitors) including cerium, Benzotriazole (BTA), and 8-Hydroxyquinoline (8H). Field-emission scanning electron microscopy (FE-SEM) and electrochemical impedance spectroscopy (EIS) are performed to investigate the barrier performance properties. The optimum conditions to achieve corrosion protective coatings for 304 stainless steel were determined. The Nyquist plots demonstrate that the activation time of the coating containing 8H as an organic healing agent shows improved behavior when compared to other coatings including cerium and BTA. Cerium as an inorganic healing agent is second and BTA is third and minimum. An increase in the impedance parameters such as resistance and capacitance as a function of immersion time is achieved in a 3.5wt.% NaCl solution by using healing agents such as BTA. Actually, over the course of immersion, the barrier performance behavior of the coatings changes and reduction of the impedance observed from the coatings containing Ce and 8H discloses deterioration of the protection system after immersion for 96h of immersion in the 3.5% NaCl solution. However, after 96h of immersion time, the concentration of chloride ions is high and causes increase in defects, micro cracks, hole on the surface of hybrid titania nanostructured coating containing Ce and 8H by destruction of coating, and also hybrid titania nanostructured coating containing BTA; BTA is released from coating to improve the resistance of passive film, which is created on the surface.

[Acute poisoning by chemical warfare agent: sulfur mustard].

PubMed

Mérat, S; Perez, J P; Rüttimann, M; Bordier, E; Lienhard, A; Lenoir, B; Pats, B

2003-02-01

To review story, mechanism of action, clinical and therapeutic bases of a sulfur mustard poisoning, by accidental, terrorism or war exposure. References were obtained from computerised bibliographic research (Medline), from personnel data (academic memoir, documents under approbation of the National Defense Office) and from the Library of Military Medical Service. Sulfur mustard is a chemical warfare agent with peace time results: leak, accidental handling, acts of terrorism. Sulfur mustard is a vesicant agent, an organochlorine agent, who alkylate DNA. Under liquid or gas form its main target are skin and lungs. Clinical effects are like burns with loss of immunity, with respiratory failure, ophthalmic, gastrointestinal and haematological signs. The last studies have improved knowledge about the mechanism of action, detection, protection and treatment. Methods for determination of sulfur mustard are based on gas chromatographic method and mass spectrometry. During sulfur mustard contamination the first priorities of treatment are to remove victims from the contaminated place and to initiate decontamination. Emergency workers and materials must take protection to avoid secondary contamination of emergency unit. With treatment of vital functions and respiratory failure, the new ways of treatment are about N-acetyl cysteine for lung injury, poly (ADP-ribose) polymerase inhibitors, calmodulin antagonists and Ca(++) chelators. Interactions between sulfur mustard and anaesthetic agents are not well known and are based on clinical observations. Emergency care unit can be confronted with sulfur mustard during accidental contamination or acts of terrorism. First and most efficacy priorities of treatment are to remove and to decontaminate victims. New means of detection and treatment are studied since several years but are not still appropriate to human victims or mass treatment.

Change in cardio-protective medication and health-related quality of life after diagnosis of screen-detected diabetes: Results from the ADDITION-Cambridge cohort.

PubMed

Black, J A; Long, G H; Sharp, S J; Kuznetsov, L; Boothby, C E; Griffin, S J; Simmons, R K

2015-07-01

Establishing a balance between the benefits and harms of treatment is important among individuals with screen-detected diabetes, for whom the burden of treatment might be higher than the burden of the disease. We described the association between cardio-protective medication and health-related quality of life (HRQoL) among individuals with screen-detected diabetes. 867 participants with screen-detected diabetes underwent clinical measurements at diagnosis, one and five years. General HRQoL (EQ5D) was measured at baseline, one- and five-years, and diabetes-specific HRQoL (ADDQoL-AWI) and health status (SF-36) at one and five years. Multivariable linear regression was used to quantify the association between change in HRQoL and change in cardio-protective medication. The median (IQR) number of prescribed cardio-protective agents was 2 (1 to 3) at diagnosis, 3 (2 to 4) at one year and 4 (3 to 5) at five years. Change in cardio-protective medication was not associated with change in HRQoL from diagnosis to one year. From one year to five years, change in cardio-protective agents was not associated with change in the SF-36 mental health score. One additional agent was associated with an increase in the SF-36 physical health score (2.1; 95%CI 0.4, 3.8) and an increase in the EQ-5D (0.05; 95%CI 0.02, 0.08). Conversely, one additional agent was associated with a decrease in the ADDQoL-AWI (-0.32; 95%CI -0.51, -0.13), compared to no change. We found little evidence that increases in the number of cardio-protective medications impacted negatively on HRQoL among individuals with screen-detected diabetes over five years. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

All-Direction Random Routing for Source-Location Privacy Protecting against Parasitic Sensor Networks.

PubMed

Wang, Na; Zeng, Jiwen

2017-03-17

Wireless sensor networks are deployed to monitor the surrounding physical environments and they also act as the physical environments of parasitic sensor networks, whose purpose is analyzing the contextual privacy and obtaining valuable information from the original wireless sensor networks. Recently, contextual privacy issues associated with wireless communication in open spaces have not been thoroughly addressed and one of the most important challenges is protecting the source locations of the valuable packages. In this paper, we design an all-direction random routing algorithm (ARR) for source-location protecting against parasitic sensor networks. For each package, the routing process of ARR is divided into three stages, i.e., selecting a proper agent node, delivering the package to the agent node from the source node, and sending it to the final destination from the agent node. In ARR, the agent nodes are randomly chosen in all directions by the source nodes using only local decisions, rather than knowing the whole topology of the networks. ARR can control the distributions of the routing paths in a very flexible way and it can guarantee that the routing paths with the same source and destination are totally different from each other. Therefore, it is extremely difficult for the parasitic sensor nodes to trace the packages back to the source nodes. Simulation results illustrate that ARR perfectly confuses the parasitic nodes and obviously outperforms traditional routing-based schemes in protecting source-location privacy, with a marginal increase in the communication overhead and energy consumption. In addition, ARR also requires much less energy than the cloud-based source-location privacy protection schemes.

In vitro protection of human lymphocytes from toxic effects of chlorpyrifos by selenium-enriched medicines

PubMed Central

Navaei-Nigjeh, Mona; Asadi, Hamidreza; Baeeri, Maryam; Pedram, Sahar; Rezvanfar, Mohammad Amin; Mohammadirad, Azadeh; Abdollahi, Mohammad

2015-01-01

Objective(s): Chlorpyrifos (CP) is a broad-spectrum organophosphorus pesticide used extensively in agricultural and domestic pest control, accounting for 50% of the global insecticidal use. In the present study, protective effects of two selenium-enriched strong antioxidative medicines IMOD and Angipars were examined in human lymphocytes treated with CP in vitro. Materials and Methods: Isolated lymphocytes were exposed to 12 µg/ml CP either alone or in combination with effective doses (ED50) of IMOD (0.2 µg/ml) and Angipars (1 µg/ml). After 3 days incubation, the viability and oxidative stress markers including cellular lipid peroxidation (LPO), myeloperoxidase (MPO), total thiol molecules (TTM), and total antioxidant power (TAP) were evaluated. Also, the levels of tumor necrosis factor-α (TNF-α), as inflammatory index along with acetylcholinesterase (AChE) activity and cell apoptosis were assessed by flow cytometry. Results: Results indicated that effective doses of IMOD and Angipars reduced CP-exposed lymphocyte mortality rate along with oxidative stress. Both agents restored CP-induced elevation of TNF-α and protected the lymphocytes from CP-induced apoptosis and necrosis. Conclusion: Overall, results confirm that IMOD and Angipars reduce the toxic effects associated with CP through free radical scavenging and protection from apoptosis and necrosis. PMID:25945242

Amelioration of the cyclophosphamide induced genotoxic damage in mice by the ethanolic extract of Equisetum arvense.

PubMed

Kour, Jasbir; Ali, Md Niamat; Ganaie, Hilal Ahmad; Tabassum, Nahida

2017-01-01

In the present study, we evaluated the potential of the plant E. arvense against the cytotoxic and mutagenic effects induced by cyclophosphamide (chemotherapeutic agent) in the bone marrow cells of mice using the Chromosome assay (CA) and Mitotic index (MI) in vivo as the biomarkers. The study was performed following 3 protocols: pre-treatment, simultaneous treatment and post-treatment with the ethanolic extract of the plant. The results demonstrated that the plant extract was not cytotoxic and mutagenic and has a protective effect against the mutagenicity induced by cyclophosphamide in pre, simultaneous and post treatments and against its cytotoxicity as well. Because of its ability to prevent chromosomal damage , E. arvense is likely to open an interesting field concerning its possible use in clinical applications, most importantly in cancer as a chemopreventive agent or even as a coadjuvant to chemotherapy to reduce the side effects associated with it.

[Rapid determination of 40 pesticide residues in fruits using gas chromatography-mass spectrometry coupled with analyte protectants to compensate for matrix effects].

PubMed

Xu, Xiuli; Zhao, Haixiang; Li, Li; Liu, Hanxia; Ren, Heling; Zhong, Weike

2012-03-01

A gas chromatography-mass spectrometry (GC-MS) method was developed for the determination of 40 pesticides in fruits. The effects of adding analyte protectants were evaluated for compensating matrix effects and the impacts on the quantitative results. A new combination of analyte protectants - Polyethylene Glycol 400 (PEG 400) and olive oil combination, which can be dissolved in acetone, was used for the quantitative analysis. The pesticides were extracted from fruit samples with acetonitrile and the extracts were cleaned up using micro-solid phase extraction. A GC-MS method in selective ion monitoring (SIM) mode coupled with large volume injection was finally developed. Using the newly developed analyte protectant combination of PEG 400 and olive oil, a good linearity was obtained in the range of 1 - 200 microg/L with coefficients better than 0.99, and the detection limits were between 0.1 - 3.0 microg/L. The mean recoveries of the pesticides were 75% - 119% with the relative standard deviation values less than 16.6% except for dimethoate. The performance of the analyte protectants was compared with matrix-matched standards calibration curves in terms of quantitative accuracy. The results showed that the method of adding analyte protectants can replace the matrix-matched standard calibration, and can also reduce the sample pretreatment. When the devel- oped method was used for the analysis of apple, peache, orange, banana, grape and other fruit samples, a good matrix compensation effect was achieved, and thus effectively reduced the bad effects of the water-soluble agents to the gas chromatographic column.

Security Measures to Protect Mobile Agents

NASA Astrophysics Data System (ADS)

Dadhich, Piyanka; Govil, M. C.; Dutta, Kamlesh

2010-11-01

The security issues of mobile agent systems have embarrassed its widespread implementation. Mobile agents that move around the network are not safe because the remote hosts that accommodate the agents initiates all kinds of attacks. These hosts try to analyze the agent's decision logic and their accumulated data. So, mobile agent security is the most challenging unsolved problems. The paper analyzes various security measures deeply. Security especially the attacks performed by hosts to the visiting mobile agent (the malicious hosts problem) is a major obstacle that prevents mobile agent technology from being widely adopted. Being the running environment for mobile agent, the host has full control over them and could easily perform many kinds of attacks against them.

The effects of Curcuma longa and curcumin on reproductive systems.

PubMed

Mohebbati, R; Anaeigoudari, A; Khazdair, M R

2017-10-26

Curcuma longa (C. longa) was used in some countries such as China and India for various medicinal purposes. Curcumin, the active component of C. longa, is commonly used as a coloring agent in foods, drugs, and cosmetics. C. longa and curcumin have been known to act as antioxidant, anti-inflammatory, anti-mutagen, and anti-carcinogenic agents. Th e attempt of the present review was to give an effort on a detailed literature survey concentrated on the protective effects of C. longa and curcumin on the reproductive organs activity. The databases such as, PubMed, Web of Science, Google Scholar, Scopus, and Iran- Medex, were considered. The search terms were "testis" or "ovary" and "Curcuma longa", "curcumin", "antioxidant effect", "anti-inflammatory effect" and "anti-cancer effect". C. longa and curcumin inhibited the production of the tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) and increased the caspases (3, 8 and 9) activities in HL-60 prostate cancer. Furthermore, C. longa and curcumin suppressed the vascular endothelial growth factor (VEGF), phosphorylated signal transducers and activators of the transcription 3 (STAT) and matrix metalloproteinase-9 (MMP-9) in ovarian cancer cell line. C. longa and curcumin might decrease the risk of cancer and other malignant diseases in the reproductive system. C. longa and curcumin have a protective effect on the reproductive organs activity such as, anti-inflammatory, anti-apoptotic, and antioxidant effects in normal cells but showed pro-apoptotic effects in the malignant cells. Therefore, different effects of C. longa and curcumin are dependent on the doses and the type of cells used in various models studied.

Blaptica dubia as sentinels for exposure to chemical warfare agents - a pilot study.

PubMed

Worek, Franz; Seeger, Thomas; Neumaier, Katharina; Wille, Timo; Thiermann, Horst

2016-11-16

The increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents a continuing threat to our societies. Early warning and detection is a key component for effective countermeasures against such deadly agents. Presently available and near term solutions have a number of major drawbacks, e.g. lack of automated, remote warning and detection of primarily low volatile chemical warfare agents. An alternative approach is the use of animals as sentinels for exposure to toxic chemicals. To overcome disadvantages of vertebrates the present pilot study was initiated to investigate the suitability of South American cockroaches (Blaptica dubia) as warning system for exposure to chemical warfare nerve and blister agents. Initial in vitro experiments with nerve agents showed an increasing inhibitory potency in the order tabun - cyclosarin - sarin - soman - VX of cockroach cholinesterase. Exposure of cockroaches to chemical warfare agents resulted in clearly visible and reproducible reactions, the onset being dependent on the agent and dose. With nerve agents the onset was related to the volatility of the agents. The blister agent lewisite induced signs largely comparable to those of nerve agents while sulfur mustard exposed animals exhibited a different sequence of events. In conclusion, this first pilot study indicates that Blaptica dubia could serve as a warning system to exposure of chemical warfare agents. A cockroach-based system will not detect or identify a particular chemical warfare agent but could trigger further actions, e.g. specific detection and increased protective status. By designing appropriate boxes with (IR) motion sensors and remote control (IR) camera automated off-site warning systems could be realized. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Aerosolized scopolamine protects against microinstillation inhalation toxicity to sarin in guinea pigs.

PubMed

Che, Magnus M; Chanda, Soma; Song, Jian; Doctor, Bhupendra P; Rezk, Peter E; Sabnekar, Praveena; Perkins, Michael W; Sciuto, Alfred M; Nambiar, Madhusoodana P

2011-07-01

Sarin is a volatile nerve agent that has been used in the Tokyo subway attack. Inhalation is predicted to be the major route of exposure if sarin is used in war or terrorism. Currently available treatments are limited for effective postexposure protection against sarin under mass casualty scenario. Nasal drug delivery is a potential treatment option for mass casualty under field conditions. We evaluated the efficacy of endotracheal administration of muscarinic antagonist scopolamine, a secretion blocker which effectively crosses the blood-brain barrier for protection against sarin inhalation toxicity. Age and weight matched male Hartley guinea pigs were exposed to 677.4 mg/m³ or 846.5 mg/ m³ (1.2 × LCt₅₀) sarin by microinstillation inhalation exposure for 4 min. One minute later, the animals exposed to 846.5 mg/ m³ sarin were treated with endotracheally aerosolized scopolamine (0.25 mg/kg) and allowed to recover for 24 h for efficacy evaluation. The results showed that treatment with scopolamine increased the survival rate from 20% to 100% observed in untreated sarin-exposed animals. Behavioral symptoms of nerve agent toxicity including, convulsions and muscular tremors were reduced in sarin-exposed animals treated with scopolamine. Sarin-induced body weight loss, decreased blood O₂ saturation and pulse rate were returned to basal levels in scopolamine-treated animals. Increased bronchoalveolar lavage (BAL) cell death due to sarin exposure was returned to normal levels after treatment with scopolamine. Taken together, these data indicate that postexposure treatment with aerosolized scopolamine prevents respiratory toxicity and protects against lethal inhalation exposure to sarin in guinea pigs.

Differential Molecular Targets for Neuroprotective Effect of Chlorogenic Acid and its Related Compounds Against Glutamate Induced Excitotoxicity and Oxidative Stress in Rat Cortical Neurons.

PubMed

Rebai, Olfa; Belkhir, Manel; Sanchez-Gomez, María Victoria; Matute, Carlos; Fattouch, Sami; Amri, Mohamed

2017-12-01

The present study has been designed to explore the molecular mechanism and signaling pathway targets of chlorogenic acid (CGA) and its main hydrolysates, caffeic (CA) and quinic acid in the protective effect against glutamate-excitotoxicity. For this purpose 8-DIV cortical neurons in primary culture were exposed to 50 μM L-glutamic acid plus 10 µM glycine, with or without 10-100 μM tested compounds. Chlorogenic acid and caffeic acid via their antioxidant properties inhibited cell death induced by glutamate in dose depended manner. However, quinic acid slightly protects neurons at a higher dose. DCF, JC-1 and Ca 2+ sensitive fluorescent dye fura-2, were used to measure intracellular ROS accumulation, mitochondrial membrane potential integration and intracellular calcium concentration [Ca 2+ ] i . Results indicate that similarly, CGA acts as a protective agent against glutamate-induced cortical neurons injury by suppressing the accumulation of endogenous ROS and restore the mitochondrial membrane potential, activate the enzymatic antioxidant system by the increase levels of SOD activity and modulate the rise of intracellular calcium levels by increasing the rise of intracellular concentrations of Ca 2+ caused by glutamate overstimulation. PKC signaling cascade appear to be engaged in this protective mechanism. Interseling, CGA and CA also exhibit antiapoptotic properties against glutamate-induced cleaved activation of pro-caspases; caspase 1,8 and 9 and calpain (PD 150606,Calpeptin and MDL 28170).These data suggest that neuroprotective activity of CGA ester may occurs throught its hydrolysate,the caffeic acid and its interaction with intracellular molecules suggesting that CGA exert its neuroprotection via its caffeoly acid group that might potentially be used as a therapeutic agent in neurodegeneratives disorders associated with glutamate excitotoxicity.

Ex vivo model exhibits protective effects of sesamin against destruction of cartilage induced with a combination of tumor necrosis factor-alpha and oncostatin M.

PubMed

Khansai, Manatsanan; Boonmaleerat, Kanchanit; Pothacharoen, Peraphan; Phitak, Thanyaluck; Kongtawelert, Prachya

2016-07-11

Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammatory arthritis. TNF-α and OSM are pro-inflammatory cytokines that play a key role in RA progression. Thus, reducing the effects of both cytokines is practical in order to relieve the progression of the disease. This current study is interested in sesamin, an active compound in sesame seeds. Sesamin has been shown to be a chondroprotective agent in osteoarthritis models. Here, we have evaluated a porcine cartilage explant as a cartilage degradation model related to RA induced by TNF-α and/or OSM in order to investigate the effects of sesamin on TNF-α and OSM in the cartilage degradation model. A porcine cartilage explant was induced with a combination of TNF-α and OSM (test group) or IL-1β and OSM (control group) followed by a co-treatment of sesamin over a long-term period (35 days). After which, the tested explants were analyzed for indications of both the remaining and the degradation aspects using glycosaminoglycan and collagen as an indicator. The combination of TNF-α and OSM promoted cartilage degradation more than either TNF-α or OSM alone and was comparable with the combination of IL-1β and OSM. Sesamin could be offering protection against cartilage degradation by reducing GAGs and collagen turnover in the generated model. Sesamin might be a promising agent as an alternative treatment for RA patients. Furthermore, the generated model revealed itself to be an impressive test model for the analysis of phytochemical substances against the cartilage degradation model for RA. The model could be used to test for the prevention of cartilage degradation in other biological agents induced with TNF-α and OSM as well.

Formulation development of the biocontrol agent Bacillus subtilis strain CPA-8 by spray-drying.

PubMed

Yánez-Mendizábal, V; Viñas, I; Usall, J; Torres, R; Solsona, C; Abadias, M; Teixidó, N

2012-05-01

To prepare commercially acceptable formulations of Bacillus subtilis CPA-8 by spray-drying with long storage life and retained efficacy to control peach and nectarine brown rot caused by Monilinia spp. CPA-8 24-h- and 72-h-old cultures were spray dried using 10% skimmed milk, 10% skimmed milk plus 10% MgSO(4) , 10% MgSO(4) and 20% MgSO(4) as carriers/protectants. All carriers/protectants gave good percentages of powder recovery (28-38%) and moisture content (7-13%). CPA-8 survival varied considerably among spray-dried 24-h- and 72-h-old cultures. Seventy-two hours culture spray dried formulations showed the highest survival (28-32%) with final concentration products of 1·6-3·3 × 10(9) CFU g(-1) , while viability of 24-h-old formulations was lower than 1%. Spray-dried 72-h-old formulations were selected to subsequent evaluation. Rehydration of cells with water provided a good recovery of CPA-8 dried cells, similar to other complex rehydration media tested. Spray-dried formulations stored at 4 ± 1 and 20 ± 1°C showed good shelf life during 6 months, and viability was maintained or slightly decreased by 0·2-0·3-log. CPA-8 formulations after 4- and 6 months storage were effective in controlling brown rot caused by Monilinia spp. on nectarines and peaches resulting in a 90-100% reduction in disease incidence. Stable and effective formulations of biocontrol agent B. subtilis CPA-8 could be obtained by spray-drying. New shelf-stable and effective formulations of a biocontrol agent have been obtained by spray-drying to control brown rot on peach. © 2012 The Authors. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

Crataegus monogyna fruit aqueous extract as a protective agent against doxorubicin-induced reproductive toxicity in male rats

PubMed Central

Shalizar Jalali, Ali; Hasanzadeh, Shapour

2013-01-01

Objective: Doxorubicin (DOX) is a broad spectrum chemotherapeutic agent used in the treatment of several malignancies. The use of DOX in clinical chemotherapy has been restricted due to its diverse toxicities, including reproductive toxicity. Crataegus monogyna (C. monogyna) is one of the oldest medicinal plants that have been shown to be cytoprotective because of scavenging free radicals. The present study was undertaken to determine whether C. monogyna fruits aqueous extract could serve as a protective agent against reproductive toxicity during DOX treatment in a rat model through antioxidant-mediated mechanisms. Materials and Methods: Male Wistar rats were allocated to four groups. Two groups of rats were treated with DOX at a dose of 4 mg/kg intraperitoneally on days 1, 7, 14, 21, and 28 (accumulated dose of 20 mg/kg). One of the groups received C. monogyna fruits aqueous extract at a dose of 20 mg/kg per day orally for 28 days along with DOX. A vehicle-treated control group and a C. monogyna control group were also included. Results: The DOX-treated group showed significant decreases in the body and organ weights and spermatogenic activities as well as many histological alterations. DOX treatment also caused a significant decrease in sperm count and motility with an increase in dead and abnormal sperms. Moreover, significant decrease in serum levels of testosterone and increased serum concentrations of FSH, LH, LDH, CPK, and SGOT were observed in DOX-treated rats. Notably, Crataegus co-administration caused a partial recovery in above-mentioned parameters. Conclusion: These findings indicated that doxorubicin can adversely damage the testicular tissue, while Crataegus co-administration could effectively prevent these adverse effects by effective inhibiting oxidative processes and restoration of antioxidant defense system. PMID:25050270

Anti-inflammatory agents and monoHER protect against DOX-induced cardiotoxicity and accumulation of CML in mice

PubMed Central

Bruynzeel, A M E; Abou El Hassan, M A; Schalkwijk, C; Berkhof, J; Bast, A; Niessen, H W M; van der Vijgh, W J F

2007-01-01

Cardiac damage is the major limiting factor for the clinical use of doxorubicin (DOX). Preclinical studies indicate that inflammatory effects may be involved in DOX-induced cardiotoxicity. Nɛ-(carboxymethyl) lysine (CML) is suggested to be generated subsequent to oxidative stress, including inflammation. Therefore, the aim of this study was to investigate whether CML increased in the heart after DOX and whether anti-inflammatory agents reduced this effect in addition to their possible protection on DOX-induced cardiotoxicity. These effects were compared with those of the potential cardioprotector 7-monohydroxyethylrutoside (monoHER). BALB/c mice were treated with saline, DOX alone or DOX preceded by ketoprofen (KP), dexamethasone (DEX) or monoHER. Cardiac damage was evaluated according to Billingham. Nɛ-(carboxymethyl) lysine was quantified immunohistochemically. Compared to saline, a 21.6-fold increase of damaged cardiomyocytes was observed in mice treated with DOX (P<0.001). Addition of KP, DEX or monoHER before DOX significantly reduced the mean ratio of abnormal cardiomyocytes in comparison to mice treated with DOX alone (P⩽0.02). In addition, DOX induced a significant increase in the number of CML-stained intramyocardial vessels per mm2 (P=0.001) and also in the intensity of CML staining (P=0.001) compared with the saline-treated group. Nɛ-(carboxymethyl) lysine positivity was significantly reduced (P⩽0.01) by DOX-DEX, DOX-KP and DOX-monoHER. These results confirm that inflammation plays a role in DOX-induced cardiotoxicity, which is strengthened by the observed DOX-induced accumulation of CML, which can be reduced by anti-inflammatory agents and monoHER. PMID:17325706

The antioxidant and antiapoptotic effects of crocin pretreatment on global cerebral ischemia reperfusion injury induced by four vessels occlusion in rats.

PubMed

Oruc, Serdar; Gönül, Yücel; Tunay, Kamil; Oruc, Oya Akpinar; Bozkurt, Mehmet Fatih; Karavelioğlu, Ergün; Bağcıoğlu, Erman; Coşkun, Kerem Senol; Celik, Sefa

2016-06-01

Cerebral ischemia reperfusion (IR) injury is a process in which oxidative and apoptotic mechanisms play a part. Neuroprotective agents to be found could work out well for the efficient and safe minimization of cerebral IR injury. Crocin is a strong antioxidant agent; however the influence of this agent on the experimental cerebral ischemia model has not been studied extensively and thus it is not well-known. The objective of our study was to investigate the antioxidant, antiapoptotic and protective effects of crocin on the global cerebral IR induced by four-vessel occlusion. A total of 30 adult female Sprague-Dawley rats were equally and randomly separated into three groups as follows: sham, IR and IR+crocin (40mg/kg/day orally for 10days). 24h after electrocauterization of bilateral vertebral arteries, bilateral common carotid arteries were occluded for 30min and reperfused for 30min. Oxidative stress parameters (TAS, TOS, OSI), haematoxylin and eosin staining, caspase-3 and hypoxia-inducible factor-1 alpha (HIF-1α) expressions and TUNEL methods were investigated. There was a significant difference between the IR and sham groups by means of OSI level, histopathological scoring, caspase-3, HIF-1α and TUNEL-positive cell parameters. We have also observed that pre-treatment with crocin reduced these parameter levels back to the baseline. The data obtained from the present study suggest that crocin may exert antiapoptotic, antioxidant and protective effects in IR-mediated brain injury induced by four-vessel occlusion. To the best of our knowledge, this would be the first study to be conducted in this field. Copyright © 2016 Elsevier Inc. All rights reserved.

The protective effect of infliximab on cisplatin-induced intestinal tissue toxicity.

PubMed

Aydin, I; Kalkan, Y; Ozer, E; Yucel, A F; Pergel, A; Cure, E; Cure, M C; Sahin, D A

2014-01-01

Cisplatin (CP) is a popular chemotherapeutic agent. However, high doses of CP may lead to severe side effects to the gastrointestinal system. The aim of this study was to investigate the protective effects of infliximab on small intestine injury induced by high doses of CP. The A total of 30 rats were equally divided into three groups, including sham (C), cisplatin (CP), and cisplatin + infliximab (CPI). The CP group was treated with 7 mg/kg intraperitoneal cisplatin, and a laparotomy was performed 5 days later. The CPI group received 7 mg/kg infliximab intraperitoneally, were administered 7 mg/kg cisplatin 4 days later, and a laparotomy was performed 5 days after receiving cisplatin. Histopathological and immunohistochemical analysis of small intestine tissue sections were performed, and superoxide dismutase, malondialdehyde, and TNF-α levels were measured. Histopathological evaluation revealed that the CP group had damage in the epithelium and connective tissue, but this damage was significantly improved in the CPI group (p < 0.05). In addition, these histopathological findings were confirmed by biochemical analyses. These results suggest that infliximab is protective against the adverse effects of CP.

Multiple protective effect of peptides released from Olea europaea and Prunus persica seeds against oxidative damage and cancer cell proliferation.

PubMed

Hernández-Corroto, Ester; Marina, María Luisa; García, María Concepción

2018-04-01

The long exposition to reactive species results in oxidative stress which has been related with the development of cancer and other serious diseases. Olea europaea and Prunus persica seeds present a high protein content and preliminary results demonstrated their high potency to obtain bioactive peptides. The protective effect against oxidative damage exerted by peptides released from Olea europaea and Prunus persica seeds has been evaluated in this work. Seed hydrolysates showed protection against oxidation through four different mechanisms: inhibition of the formation of hydroxyl radicals, scavenging of free radicals, reduction of oxidizing compounds, and inhibition of lipid peroxidation. Moreover, seed hydrolysates also reduced the oxidative stress induced by an oxidizing agent on human cancer cells. Despite protection evaluated by individual mechanisms seemed to be significantly affected by the seed genotype, overall protection of seed hydrolysates was not so different. Seeds hydrolysates were not cytotoxic on normal cells but they demonstrated antiproliferative effect on human cancer cells (HeLa, PC-3, and HT-29). Peptides in all seed hydrolysates were sequenced by RP-HPLC-ESI-Q-TOF. Eighteen common peptides were observed among olive seed hydrolysates while a wider variability was observed among Prunus seed hydrolysates. Copyright © 2018 Elsevier Ltd. All rights reserved.

Local Melatoninergic System as the Protector of Skin Integrity

PubMed Central

Slominski, Andrzej T.; Kleszczyński, Konrad; Semak, Igor; Janjetovic, Zorica; Żmijewski, Michał A.; Kim, Tae-Kang; Slominski, Radomir M.; Reiter, Russel J.; Fischer, Tobias W.

2014-01-01

The human skin is not only a target for the protective actions of melatonin, but also a site of melatonin synthesis and metabolism, suggesting an important role for a local melatoninergic system in protection against ultraviolet radiation (UVR) induced damages. While melatonin exerts many effects on cell physiology and tissue homeostasis via membrane bound melatonin receptors, the strong protective effects of melatonin against the UVR-induced skin damage including DNA repair/protection seen at its high (pharmocological) concentrations indicate that these are mainly mediated through receptor-independent mechanisms or perhaps through activation of putative melatonin nuclear receptors. The destructive effects of the UVR are significantly counteracted or modulated by melatonin in the context of a complex intracutaneous melatoninergic anti-oxidative system with UVR-enhanced or UVR-independent melatonin metabolites. Therefore, endogenous intracutaneous melatonin production, together with topically-applied exogenous melatonin or metabolites would be expected to represent one of the most potent anti-oxidative defense systems against the UV-induced damage to the skin. In summary, we propose that melatonin can be exploited therapeutically as a protective agent or as a survival factor with anti-genotoxic properties or as a “guardian” of the genome and cellular integrity with clinical applications in UVR-induced pathology that includes carcinogenesis and skin aging. PMID:25272227

Antioxidant and Cytoprotective Activities of Fucus spiralis Seaweed on a Human Cell in Vitro Model

PubMed Central

Pinteus, Susete; Silva, Joana; Alves, Celso; Horta, André; Thomas, Olivier P.; Pedrosa, Rui

2017-01-01

Antioxidants play an important role as Reactive Oxygen Species (ROS) chelating agents and, therefore, the screening for potent antioxidants from natural sources as potential protective agents is of great relevance. The main aim of this study was to obtain antioxidant-enriched fractions from the common seaweed Fucus spiralis and evaluate their activity and efficiency in protecting human cells (MCF-7 cells) on an oxidative stress condition induced by H2O2. Five fractions, F1–F5, were obtained by reversed-phase vacuum liquid chromatography. F3, F4 and F5 revealed the highest phlorotannin content, also showing the strongest antioxidant effects. The cell death induced by H2O2 was reduced by all fractions following the potency order F4 > F2 > F3 > F5 > F1. Only fraction F4 completely inhibited the H2O2 effect. To understand the possible mechanisms of action of these fractions, the cellular production of H2O2, the mitochondrial membrane potential and the caspase 9 activity were studied. Fractions F3 and F4 presented the highest reduction on H2O2 cell production. All fractions decreased both caspase-9 activity and cell membrane depolarization (except F1). Taken all together, the edible F. spiralis reveal that they provide protection against oxidative stress induced by H2O2 on the human MCF-7 cellular model, probably acting as upstream blockers of apoptosis. PMID:28146076

Cytokines in immunogenic cell death: Applications for cancer immunotherapy.

PubMed

Showalter, Anne; Limaye, Arati; Oyer, Jeremiah L; Igarashi, Robert; Kittipatarin, Christina; Copik, Alicja J; Khaled, Annette R

2017-09-01

Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions. Natural Killer (NK) cells are a front-line defense against drug-resistant tumors and can provide tumoricidal activity to enhance tumor immune surveillance. Cytokines like IFN-γ or TNF play a crucial role in creating an immunogenic microenvironment and therefore are key players in the fight against metastatic cancer. To this end, a group of anthracyclines or treatments like photodynamic therapy (PDT) exert their effects on cancer cells in a manner that activates the immune system. This process, known as immunogenic cell death (ICD), is characterized by the release of membrane-bound and soluble factors that boost the function of immune cells. This review will explore different types of ICD inducers, some in clinical trials, to demonstrate that optimizing the cytokine response brought about by treatments with ICD-inducing agents is central to promoting anti-cancer immunity that provides long-lasting protection against disease recurrence and metastasis. Copyright © 2017. Published by Elsevier Ltd.

Performance of Metarhizium anisopliae-treated foam in combination with Phytoseiulus longipes Evans on Tetranychus evansi Baker & Pritchard (Acari: Tetranychidae).

PubMed

Azandémè Hounmalon, Ginette Y; Maniania, Nguya K; Niassy, Saliou; Fellous, Simon; Kreiter, Serge; Delétré, Emilie; Fiaboe, Komi K; Martin, Thibaud

2018-05-13

Tetranychus evansi (Te) is an exotic pest of solanaceous crops in Africa. The predatory mite Phytoseiulus longipes (Pl) and the fungus Metarhizium anisopliae (Ma), are potential biocontrol agents of Te. The present study investigated efficacy of fungus-treated foam placed above or below the third Te-infested tomato leaf. The persistence of fungus-treated foam and the performance of Pl with or without fungus-treated foam were evaluated. The fungus-treated foam was effective when Te infestation was below the third tomato leaf as no damage was recorded on all upper tomato leaves up to 30 days post-treatment. However, in the control treatments, the infestation increased considerably from 9±0.3% to 100±0% at 15 days post-treatment. The reuse of the fungus-treated foam at 15, 30 and 45 days post-treatment resulted in 19±1.4%, 25±1.2% and 54±2.1% respective infestation by Te. The fungus-treated foam and Pl alone are efficient, but there is no benefit to combinting both against Te. The fungus-treated foam is an effective method to optimize the use of Ma in screenhouse conditions. These two control agents could be integrated in an IPM strategy for crops protection. However, these results need to be confirmed in large field trials. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[To Protect Corneal Transparency against Diseases].

PubMed

Usui, Tomohiko

2016-03-01

To protect corneal transparency, we tried to develop a new therapeutic strategy for corneal neovascularization, corneal scar, and TGFBI-related corneal dystrophy using nucleic acid drug. 1. The expression of angiopietin-like protein 2 (Angptl2) markedly increased in the neovascularized corneas compared to the normal cornea, and Angtpl2 was(a potent inducer of inflammatory corneal neovascularization. We have produced a single-stranded proline-modified short hairpin anti-Angptl2 ribonucleric acid interference (RNAi) molecule that is carried in a lipid nanoparticle for topical application. We have found this agent can penetrate all layers of the cornea. Angptl2 mRNA expression and corneal neovascularization were inhibited in a mouse alkari injury model by topical application of this agent. Thus, this modified RNAi agent is a new topical formulation for use against corneal neovascularization and scar. 2. Human umbilical vein endothelial cells (HUVECs) were cultured with human corneal keratocytes under serum-free conditions. We performed microarray gene-expression analysis in the coculture system and selected angiopoietin-like protein 7 (Angptl7). In vivo, intrastromal injections of an anti-Angptl7 RNAi agent into the avascular corneal stroma of mice resulted in the growth of blood vessels. Further, we examined the effects of Angptl7 on corneal nerves using culture rat trigeminal cells and this molecule had neurotrophic property on the cornea. Thus, Angpt17 is a unique molecule, which contain its bilateral character (anti-angiogenic and neurotrophic) in the cornea; an agonistic nucleic acid drug for Angptl7 may be a new therapeutic tool for protecting corneal transparency. 3. We examined local gene editing for TGFBI-related corneal dystrophy using CRISPR-Cas9 mediated homology directed repair (HDR). Cultured corneal keratocytes were obtained from a patient of R124H granular dystrophy. The R124H gene arrangement was corrected by a tranfection of guide RNA and HDR repair template single strand DNA in vitro. Thus, CRISPR-Cas9 medi-ated HDR could be a future radical treatment for TGFBI-related corneal dystrophy.

Dietary selenium protects adiponectin knockout mice against chronic inflammation induced colon cancer.

PubMed

Saxena, Arpit; Fayad, Raja; Kaur, Kamaljeet; Truman, Samantha; Greer, Julian; Carson, James A; Chanda, Anindya

2017-04-03

Selenium (Se) is an essential dietary micronutrient that has been examined for protection against different types of cancers including colon cancer. Despite an established inverse association between Se and chronic inflammation induced colon cancer (CICC), the mechanistic understanding of Se's protective effects requires additional in-vivo studies using preclinical animal models of CICC. Adiponectin (APN) is an adipocytokine that is protective against CICC as well. However, its role in the anti-mutagenic effects of the Se-diet remains unknown. To address this knowledge gap, here we examine the ability of dietary Se in reducing CICC in APN knockout mice (KO) and its wild-type C57BL/6. CICC was induced with the colon cancer agent 1,2 dimethyl hydrazine (DMH) along with dextran sodium sulfate (DSS). Se-enhanced diet increased selenoproteins, Gpx-1 and Gpx-2, in the colon tissues, thereby reducing oxidative stress. Se-mediated reduction of CICC was evident from the histopathological studies in both mouse models. In both mice, reduction in inflammation and tumorigenesis associated well with reduced p65 phosphorylation and elevated 53 phosphorylation. Finally, we show that in both models Se-administration promotes goblet cell differentiation with a concomitant increase in the levels of associated proteins, Muc-2 and Math-1. Our findings suggest that Se's protection against CICC involves both colonic epithelial protection and anti-tumor effects that are independent of APN.

76 FR 16297 - Aspergillus flavus

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-23

... commodities, when applied/used as an antifungal agent. The Arizona Cotton Research and Protection Council... petition (PP 9E7662) by the Arizona Cotton Research and Protection Council, 3721 East Wier Ave., Phoenix... Cotton Research and Protection Council, which is available in the docket, http://www.regulations.gov...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fornasiero, Francesco

Aiming to protect soldiers from biological and chemical threats, a team of Lawrence Livermore National Laboratory scientists have created a material that is highly breathable yet protective from biological agents. This material is the first key component of futuristic smart uniforms that also will respond to and protect from environmental chemical hazards.

Chondro-Protective and Antiarthritic Effects of Sulfonamido-Based Gallate-ZXHA-TC in Vitro and in Vivo.

PubMed

Lu, Zhenhui; Wu, Huayu; Lin, Xiao; Liu, Buming; Lin, Cuiwu; Zheng, Li; Zhao, Jinmin

2016-06-17

The effects of gallic acid (GA) on arthritis are limited by weak antioxidant effects and inferior biological properties of GA. We recently described a new series of synthesized GA derivatives by coupling with sulfonamides. Among these analogs, a novel compound synthesized from GA and sulfadimoxine (SDM) named ZXHA-TC exhibited the most robust anti-inflammatory potential. In this current study, the chondro-protective and antiarthritic effects of ZXHA-TC were investigated both in vitro and in vivo. In the in vitro study, ZXHA-TC exerted chondro-protective effects as evidenced by promoting cell proliferation and the maintaining of the phenotype of articular chondrocytes treated with interleukin-1-beta (IL-1β). The potential of ZXHA-TC to slow the progress of osteoarthritis (OA) was suggested by a reduction in matrix metalloproteinases (MMPs) and the up-regulation of the tissue inhibitor of metalloproteinase-1 (TIMP-1). In a rabbit anterior cruciate ligament transaction (ACLT) model of OA, ZXHA-TC exerted a protective effect on arthritis as assessed by macroscopic scores, histological, qRT-PCR, and immunohistochemical analyses. The effects of ZXHA-TC on inhibiting the production of inflammatory mediators in OA may be mediated partly by the suppression of the PI3K/AKT pathway or MAPK cascades, leading to NF-κB inactivation. Thus, this study indicates that ZXHA-TC may be developed as a potential therapeutic agent for OA.

[Perspectives in the treatments of poisonings by organophosphorus insecticides and warfare nerve agents].

PubMed

Sogorb-Sánchez, M A; Vilanova-Gisbert, E; Carrera-González, V

Organophosphorus compounds are worldwide employed as insecticides and are yearly responsible of several millions of poisonings. The chemical structure of most of the warfare nerve agents also corresponds with an organophosphorus compound. Organophosphorus insecticides and warfare nerve agents exert their main toxicological effects through inhibition of acetylcholinesterase. Current treatments of patients poisoned with organophosphorus compounds include atropine (in order to protect muscarinic receptors), oximes (in order to accelerate the reactivation of the inhibited acetylcholinesterase) and benzodiazepines (in order to avoid convulsions). The administration of phosphotriesterases (enzymes involved in the detoxication of organophosphorus compounds through hydrolysis) is a very effective treatment against poisonings by organophosphorus insecticides and warfare nerve agents. There are experimental preventive treatments based on the simultaneous administration of carbamates and certain antimuscarinic drugs, different from atropine, which notably improve the efficacy of the classical treatments applied after poisonings by warfare nerve agents. The treatments based in the administration of phosphotriesterases might be the response to the call of the World Health Organization for searching new treatments with capability to reduce the high mortality recorded in the cases of poisonings by organophosphorus compounds. These treatments can be applied in a preventive way without the intrinsic neurotoxicity associated to the preventive treatments based on carbamates and antimuscarinic drugs. Therefore, these treatments are specially interesting for people susceptible to suffer severe exposures, i.e. sprayers in the farms.

A Novel Anti-Pollution Filter for Volatile Agents During Cardiopulmonary Bypass: Preliminary Tests.

PubMed

Nigro Neto, Caetano; Landoni, Giovanni; Tardelli, Maria Angela

2017-08-01

Concerns regarding pollution of the operating room by volatile anesthetics and effects on atmospheric ozone depletion exist. Volatile agents commonly are used during cardiopulmonary bypass to provide anesthesia independent of any supposed myocardial protective effects. The authors' aim was to create and to assess the performance of a prototype filter for volatile agents to be connected to the cardiopulmonary bypass circuit to avoid the emission of volatile agents to the operating room, and also to the environment without causing damage to the membrane oxygenator. Observational trial. University hospital. Prototype filter for volatile agents. The prototype filter was tested in a single ex vivo experiment. The main data measured during the test were pressure drop to detect interference with the performance of the oxygenator, back pressure to detect overpressure to the outlet gas jacket of the oxygenator, analysis of exhaled sevoflurane after the membrane oxygenator, and after the filter to detect any presence of sevoflurane. The prototype filter adsorbed the sevoflurane eliminated through the outlet portion of the oxygenator. During the entire test, the back pressure remained constant (4 mmHg) and pressure drop varied from 243 mmHg to 247 mmHg. The prototype filter was considered suitable to absorb the sevoflurane, and it did not cause an overpressure to the membrane oxygenator during the test. Copyright © 2017 Elsevier Inc. All rights reserved.

Estimated Chemical Warfare Agent Surface Clearance Goals for Remediation Pre-Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dolislager, Frederick; Bansleben, Dr. Donald; Watson, Annetta Paule

2010-01-01

Health-based surface clearance goals, in units of mg/cm2, have been developed for the persistent chemical warfare agents sulfur mustard (HD) and nerve agent VX as well as their principal degradation products. Selection of model parameters and critical receptor (toddler child) allow calculation of surface residue estimates protective for the toddler child, the general population and adult employees of a facilty that has undergone chemical warfare agent attack.

Protection Against the Acute and Delayed Toxicity of Mustards and Mustard-Like Compounds

DTIC Science & Technology

1987-02-01

environ- mental agents can be more important than modification at the major alkylation sites, an important inicial objective of this work was to identify...position of guanine in DNA. A mechanism has been discovered for certain antitumor agents which leads to DNA cross-linking following alkylation of the O...been discovered. Simple monofunctional alkylating agents , including methylating agents , appear to cause cross-link- ing through the reactions of the

Study to Determine the CB (Chemical/Biological) Threat and Define Alternative Crew Protection Systems for the Advanced Attack Helicopter (AAH). Volume 1

DTIC Science & Technology

1980-12-01

NTIS GRA&I DTIC TAR Unannou.nced _ Just if i cat i o Distribution/ Availability Codes Avail and/or Dist Special ii -.- ,-4. ,S... -. UNCLASSIFIED...fighting ability. U Biological agents consist of living micro-organisms including bacteria, rickettsia and viruses . These agents are affected by their...six hours when worn with a protective hood. While virus particles are normally extremely minute, it is assumed in this study that they must be

Topical Resiquimod Protects against Visceral Infection with Leishmania infantum chagasi in Mice

PubMed Central

Craft, Noah; Birnbaum, Ron; Quanquin, Natalie; Erfe, Marie Crisel B.; Quant, Cara; Haskell, Jacquelyn

2014-01-01

New prevention and treatment strategies are needed for visceral leishmaniasis, particularly ones that can be deployed simply and inexpensively in areas where leishmaniasis is endemic. Synthetic molecules that activate Toll-like receptor 7 and 8 (TLR7/8) pathways have previously been demonstrated to enhance protection against cutaneous leishmaniasis. We initially sought to determine whether the TLR7/8-activating molecule resiquimod might serve as an effective vaccine adjuvant targeting visceral leishmaniasis caused by infection with Leishmania infantum chagasi. Resiquimod was topically applied to the skin of mice either prior to or after systemic infection with L. infantum chagasi, and parasite burdens were assessed. Surprisingly, topical resiquimod application alone, in the absence of vaccination, conferred robust resistance to mice against future intravenous challenge with virulent L. infantum chagasi. This protection against L. infantum chagasi infection persisted as long as 8 weeks after the final topical resiquimod treatment. In addition, in mice with existing infections, therapeutic treatment with topical resiquimod led to significantly lower visceral parasite loads. Resiquimod increased trafficking of leukocytes, including B cells, CD4+ and CD8+ T cells, dendritic cells, macrophages, and granulocytes, in livers and spleens, which are the key target organs of visceralizing infection. We conclude that topical resiquimod leads to systemic immune modulation and confers durable protection against visceralizing L. infantum chagasi infection, in both prophylactic and therapeutic settings. These studies support continued studies of TLR-modulating agents to determine mechanisms of protection and also provide a rationale for translational development of a critically needed, novel class of topical, preventative, and therapeutic agents for these lethal infections. PMID:25030052

Hamamelitannin from Hamamelis virginiana inhibits the tumour necrosis factor-alpha (TNF)-induced endothelial cell death in vitro.

PubMed

Habtemariam, Solomon

2002-01-01

The tumour necrosis factor-alpha (TNF) inhibitory activity of hamamelitannin from Hamamelis virginiana was investigated by assessing the TNF-mediated EAhy926 endothelial cell death and adhesiveness to monocytes. Treatment of the cells by TNF (25 ng/ml) and actinomycin D (0.1ng/ml) resulted in significant DNA fragmentation (34+/-0.6, n=4) and cytotoxicity (97+/-4.5%, n=6) following treatment for 8 and 24h, respectively. One to 100 microM concentrations of hamamelitannin inhibited the TNF-mediated endothelial cell death and DNA fragmentation in a dose-dependent manner. One hundred % protection against TNF-induced DNA fragmentation and cytotoxicity was obtained for hamamelitannin concentrations higher than 10 microM. The protective effect of hamamelitannin was comparable with that of a related compound epigallocatechin gallate while gallic acid was a weak protective agent (<40% protection). EAhy926 endothelial cells upregulated (by 4- to 7-fold) the surface expression of intercellular adhesion molecule-1 (ICAM-1) and adhesiveness to monocytic U937 cells after treatment with TNF (0.5ng/ml) for 6 or 24h. Concentrations (1-100 microM) of hamamelitannin that inhibited the TNF-mediated cell death and DNA fragmentation, however, failed to inhibit the TNF-induced ICAM-1 expression and EAhy926 cell adhesiveness to U937 cells. Thus, hamamelitannin inhibits the TNF-mediated endothelial cell death without altering the TNF-induced upregulation of endothelial adhesiveness. The observed anti-TNF activity of hamamelitannin may explain the antihamorrhaegic use of H. virginiana in traditional medicine and its claimed use as a protective agent for UV radiation.

A Comparative Analysis of the Photo-Protective Effects of Soy Isoflavones in Their Aglycone and Glucoside Forms

PubMed Central

Iovine, Barbara; Iannella, Maria Luigia; Gasparri, Franco; Giannini, Valentina; Monfrecola, Giuseppe; Bevilacqua, Maria Assunta

2012-01-01

Isoflavones exist in nature predominantly as glucosides such as daidzin or genistin and are rarely found in their corresponding aglycone forms daidzein and genistein. The metabolism and absorption of isoflavones ingested with food is well documented, but little is known about their use as topical photo-protective agents. The aim of this study was to investigate in a comparative analysis the photo-protective effects of isoflavones in both their aglycone and glucoside forms. In human skin fibroblasts irradiated with 60 mJ/cm2 ultraviolet B (UVB), we measured the expression levels of COX-2 and Gadd45, which are involved in inflammation and DNA repair, respectively. We also determined the cellular response to UVB-induced DNA damage using the comet assay. Our findings suggest that both the isoflavone glucosides at a specific concentration and combination with an aglycone mixture exerted an anti-inflammatory and photo-protective effect that prevented 41% and 71% of UVB-induced DNA damage, respectively. The advantages of using either isoflavone glucosides or an aglycone mixture in applications in the field of dermatology will depend on their properties and their different potential uses. PMID:23211668

Evaluation of the effect of a home bleaching agent on surface characteristics of indirect esthetic restorative materials--part II microhardness.

PubMed

Torabi, Kianoosh; Rasaeipour, Sasan; Ghodsi, Safoura; Khaledi, Amir Ali Reza; Vojdani, Mahroo

2014-07-01

The exponential usage of esthetic restorative materials is beholden to society needs and desires. Interaction between the bleaching agents and the esthetic restorative materials is of critical importance. This in vitro study has been conducted to evaluate the effect of a home bleaching agent, carbamide peroxide (CP) 38%, on the microhardness of the fiber reinforced composite (FRC), overglazed, autoglazed, or polished porcelain specimens. For overglazed, autoglazed, polished ceramics and also FRC cylindrical specimens (n = 20 per group) were prepared. The specimens were stored in distilled water at 37°C for 48 hours prior to testing. Six samples from each group were selected randomly as negative controls which were stored in distilled water at 37°C that was changed daily. CP 38% was applied on the test specimens for 15 minutes, twice a day for 14 days. By using Knoop-microhardness tester microhardness testing for baseline, control and test specimens was conducted. Data were statistically analyzed using paired t-test, Mann-Whitney test, and Kruskal-Wallis test. Home bleaching significantly decreased the surface microhardness of all the test samples (p < 0.05), whereas the control groups did not show statistically significant changes after 2 weeks. The polished porcelain and polished composite specimens showed the most significant change in microhard-ness after bleaching process (p < 0.05). Although the type of surface preparation affects the susceptibility of the porcelain surface to the bleaching agent, no special preparation can preclude such adverse effects. The contact of home bleaching agents with esthetic restorative materials is unavoidable. Therefore protecting these restorations from bleaching agents and reglazing or at least polishing the restorations after bleaching is recommended.

Fire Protection Specialist, Blocks I, II, & III, 17-2. Military Curriculum Materials for Vocational and Technical Education.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This military-developed text contains the first three blocks of a five-block course for use in training fire protection specialists. Covered in the individual volumes are the following topics: fire protection objectives and responsibilities (fire protection and occupational safety, extinguishing agents, principles and theory of combustion, natural…

Yersinia pestis caf1 variants and the limits of plague vaccine protection.

PubMed

Quenee, Lauriane E; Cornelius, Claire A; Ciletti, Nancy A; Elli, Derek; Schneewind, Olaf

2008-05-01

Yersinia pestis, the highly virulent agent of plague, is a biological weapon. Strategies that prevent plague have been sought for centuries, and immunization with live, attenuated (nonpigmented) strains or subunit vaccines with F1 (Caf1) antigen is considered effective. We show here that immunization with live, attenuated strains generates plague-protective immunity and humoral immune responses against F1 pilus antigen and LcrV. Y. pestis variants lacking caf1 (F1 pili) are not only fully virulent in animal models of bubonic and pneumonic plague but also break through immune responses generated with live, attenuated strains or F1 subunit vaccines. In contrast, immunization with purified LcrV, a protein at the tip of type III needles, generates protective immunity against the wild-type and the fully virulent caf1 mutant strain, in agreement with the notion that LcrV can elicit vaccine protection against both types of virulent plague strains.

Pain expressiveness and altruistic behavior: an exploration using agent-based modeling.

PubMed

de C Williams, Amanda C; Gallagher, Elizabeth; Fidalgo, Antonio R; Bentley, Peter J

2016-03-01

Predictions which invoke evolutionary mechanisms are hard to test. Agent-based modeling in artificial life offers a way to simulate behaviors and interactions in specific physical or social environments over many generations. The outcomes have implications for understanding adaptive value of behaviors in context. Pain-related behavior in animals is communicated to other animals that might protect or help, or might exploit or predate. An agent-based model simulated the effects of displaying or not displaying pain (expresser/nonexpresser strategies) when injured and of helping, ignoring, or exploiting another in pain (altruistic/nonaltruistic/selfish strategies). Agents modeled in MATLAB interacted at random while foraging (gaining energy); random injury interrupted foraging for a fixed time unless help from an altruistic agent, who paid an energy cost, speeded recovery. Environmental and social conditions also varied, and each model ran for 10,000 iterations. Findings were meaningful in that, in general, contingencies that evident from experimental work with a variety of mammals, over a few interactions, were replicated in the agent-based model after selection pressure over many generations. More energy-demanding expression of pain reduced its frequency in successive generations, and increasing injury frequency resulted in fewer expressers and altruists. Allowing exploitation of injured agents decreased expression of pain to near zero, but altruists remained. Decreasing costs or increasing benefits of helping hardly changed its frequency, whereas increasing interaction rate between injured agents and helpers diminished the benefits to both. Agent-based modeling allows simulation of complex behaviors and environmental pressures over evolutionary time.

Coastal Changes, Eastern Lake Michigan, 1970-74.

DTIC Science & Technology

1981-01-01

an effective shore protection agent during the stormiest months of January, February, and March. Till and mixed till bluffs tended to erode less than...final report of a 4-year study of 17 profile lines located along the eastern shore of Lake Michigan. The work v-as carried out under the coastal...26 5 Sediment statistics sum~mary, eastern Lake Michigan (October 1973 to December 1974

Direct and protective effects of single or combined addition of vincristine and ε-viniferin on human HepG2 cellular oxidative stress markers in vitro.

PubMed

Tarhan, Seda; Özdemir, Filiz; İncesu, Zerrin; Demirkan, Emine Sütken

2016-08-01

The objective of this study is to examine the direct effects of low doses and high doses of ε-viniferin, a substance known to be an antioxidant, and vincristine sulphate, a chemotherapeutic agent, alone and in combination [ε-viniferin + vincristine] on HepG2 cell strain, as well as evaluate oxidative stress after incubation periods of 3, 6, and 24 h. Direct effect was determined right after the incubation period; however, for protective effect, antioxidant protection response was determined after the treatment for 1 h with 500 μM H2O2, which is an oxidative stressor. For this purpose, superoxide dismutase was determined for enzyme activity, and lipid hydroperoxide (LPO) and reduced glutathione concentrations were studied as indicators of oxidative stress. Results show that low [3.63 µM vincristine + 3.75 µM ε-viniferin] and high [11.25 µM vincristine + 15.8 µM ε-viniferin] doses of combination groups showed similar direct antioxidant effect on LPO levels as protective when compared to the H2O2 control group (p < 0.05). Superoxide dismutase enzyme showed a direct antioxidant effect in low and high dose combination groups. In addition, when the incubation period was increased to 24 h, a protective effect was observed in both dose groups (p < 0.05). Reduced glutathione activities showed a direct effect in the low dose combination group, and a protective effect in both the low and high doses in the 24 h. These results show that combined usage of drugs in HepG2 cell strain possesses a protective effect against exogenically produced oxidative stress conditions.

Treatment of Mengovirus Infection in Mice with Statolon

PubMed Central

Pindak, Frank F.; Schmidt, Jerome P.

1967-01-01

A single intraperitoneal injection of statolon was shown to exert a therapeutic effect on mice previously injected with the large plaque-forming variant of mengovirus. The ld50 and survival time data demonstrated that such treatment was effective when given 2 to 48 hr after infection. No protective effect was apparent when statolon was administered 3, 4, or 5 days after the viral challenge. It was concluded that statolon, or other similar interferon inducers, may be of therapeutic value in instances of accidental or other known exposure to hazardous viral agents. PMID:4294823

Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacNaughton, W.K.; Wallace, J.L.; Cirino, G.

1989-01-01

The role that nitric oxide, an endothelium-derived relaxing factor, may play in the regulation of gastric mucosal defense was investigated by assessing the potential protective actions of this factor against the damage caused by ethanol in an ex vivo chamber preparation of the rat stomach. Topical application of glyceryl trinitrate and sodium nitroprusside, which have been shown to release nitric oxide, markedly reduced the area of 70% ethanol-induced hemorrhagic damage. Topical application of a 0.01% solution of authentic nitric oxide also significantly reduced the severity of mucosal damage. Pretreatment with indomethacin precluded the involvement of endogenous prostaglandins in the protectivemore » effects of these agents. The protective effects of NO were transient, since a delay of 5 minutes between NO administration and ethanal administration resulted in a complete loss of the protective activity. The protection against ethanol afforded by 10 ug/ml nitroprusside could be completely reversed by intravenous infusion of either 1% methylene blue or 1 mM hemoglobin, both of which inhibit vasodilation induced by nitric oxide. Intravenous infusion of 1% methylene blue significantly increased the susceptibility of the mucosa to damage induced by topical 20% ethanol.« less

Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses.

PubMed

Guo, Ruo-Bing; Wang, Guo-Feng; Zhao, An-Peng; Gu, Jun; Sun, Xiu-Lan; Hu, Gang

2012-01-01

Paeoniflorin (PF), the principal component of Paeoniae Radix prescribed in traditional Chinese medicine, has been reported to exhibit many pharmacological effects including protection against ischemic injury. However, the mechanisms underlying the protective effects of PF on cerebral ischemia are still under investigation. The present study showed that PF treatment for 14 days could significantly inhibit transient middle cerebral artery occlusion (MCAO)-induced over-activation of astrocytes and microglia, and prevented up-regulations of pro-inflamamtory mediators (TNFα, IL-1β, iNOS, COX(2) and 5-LOX) in plasma and brain. Further study demonstrated that chronic treatment with PF suppressed the activations of JNK and p38 MAPK, but enhanced ERK activation. And PF could reverse ischemia-induced activation of NF-κB signaling pathway. Moreover, our in vitro study revealed that PF treatment protected against TNFα-induced cell apoptosis and neuronal loss. Taken together, the present study demonstrates that PF produces a delayed protection in the ischemia-injured rats via inhibiting MAPKs/NF-κB mediated peripheral and cerebral inflammatory response. Our study reveals that PF might be a potential neuroprotective agent for stroke.

Influence of citric acid on the surface texture of glass ionomer restorative materials

PubMed Central

Reddy, Dappili Swami Ranga; Kumar, Ramachandran Anil; Venkatesan, Sokkalingam Mothilal; Narayan, Gopal Shankar; Duraivel, Dasarathan; Indra, Rajamani

2014-01-01

Aim: This study determined the effectiveness of G-coat plus surface protective agent over petroleum jelly on the surface texture of conventional Glass ionomer restorative materials. Materials and Methods: Three chemically cured conventional glass ionomer restorative materials type II, type IX and ketac molar were evaluated in this study. Sixty specimens were made for each restorative material. They were divided into two groups of thirty specimens each. Of the sixty specimens, thirty were coated with G-coat plus (a nano-filler coating) and the rest with petroleum jelly. Thirty samples of both protective coating agents were randomly divided into six groups of five specimens and conditioned in citric acid solutions of differing pH (pH 2, 3, 4, 5, 6 & 7). Each specimen was kept in citric acid for three hours a day, and the rest of time stored in salivary substitute. This procedure was repeated for 8 days. After conditioning, the surface roughness (Ra, μm) of each specimen was measured using a surface profilometer (Taylor & Habson, UK). Data was analyzed using one-way analysis of variance (ANOVA) and Tukey's HSD test at a significance level of 0.05. Results: The surface textures of all the tested glass ionomer restorative materials protected with G-coat plus were not significantly affected by acids at low pH. The surface textures of all the tested glass ionomer restorative materials protected with petroleum jelly coating were significantly affected by acids at low pH. Conclusion: The effects of pH on the surface texture of glass ionomer restoratives are material dependent. Among all the materials tested the surface texture of Type II GIC (Group I) revealed marked deterioration when conditioned in solutions of low pH and was statistically significant. Hence, a protective coating either with G-coat plus or with light polymerized low viscosity unfilled resin adhesives is mandatory for all the glass ionomer restorations to increase the wear resistance of the restorative materials. PMID:25298643