PubMed | Naval Medical Research Unit San Antonio, Ohio State University and Budapest University of Technology and Economics
Type: | Journal: International journal of nanomedicine | Year: 2016
The addition of antibacterial functionality to dental resins presents an opportunity to extend their useful lifetime by reducing secondary caries caused by bacterial recolonization. In this study, the potential efficacy of nitrogen-doped titanium dioxide nanoparticles for this purpose was determined. Nitrogen doping was carried out to extend the ultraviolet absorbance into longer wavelength blue light for increased biocompatibility. Titanium dioxide nanoparticles (approximately 20-30 nm) were synthesized with and without nitrogen doping using a sol-gel method. Ultraviolet-Visible spectroscopy indicated a band of trap states, with increasing blue light absorbance as the concentration of the nitrogen dopant increased. Electron paramagnetic resonance measurements indicated the formation of superoxide and hydroxyl radicals upon particle exposure to visible light and oxygen. The particles were significantly toxic to
Rall J.M.,General Dynamics Corporation |
Cox J.M.,Eagle Applied science |
Songer A.G.,Naval Diving and Salvage Training Center |
Cestero R.F.,Naval Medical Research Unit San Antonio |
Ross J.D.,Science and Technology Office WilfordHallAmbulatory SurgicalCenter
Journal of Trauma and Acute Care Surgery | Year: 2013
BACKGROUND: Uncontrolled hemorrhage is the leading cause of preventable death on the battlefield. The development, testing, and application of novel hemostatic dressings may lead to a reduction of prehospital mortality through enhanced point-of-injury hemostatic control. This study aimed to determine the efficacy of currently available hemostatic dressings as compared with the current Committee for Tactical Combat Casualty Care Guidelines standard of treatment for hemorrhage control (QuikClot Combat Gauze [QCG]). METHODS: The femoral artery of anesthetized Yorkshire pigs was isolated and punctured. Free bleeding was allowed to proceed for 45 seconds before packing of QCG, QuikClot Combat Gauze XL (QCX), Celox Trauma Gauze (CTG), Celox Gauze (CEL), or HemCon ChitoGauze (HCG), into the wound. After 3 minutes of applied, direct pressure, fluid resuscitation was administered to elevate and maintain a mean arterial pressure of 60 mm Hg or greater during the 150-minute observation time. Animal survival, hemostasis, and blood loss were measured as primary end points. Hemodynamic and physiologic parameters, along with markers of coagulation, were recorded and analyzed. RESULTS: Sixty percent of QCG-treated animals (controls) survived through the 150-minute observation period. QCX, CEL, and HCG were observed to have higher rates of survival in comparison to QCG (70%, 90%, and 70% respectively), although these results were not found to be of statistical significance in pairwise comparison to QCG. Immediate hemostasis was achieved in 30% of QCG applications, 80% of QCX, 70% of CEL, 60% of HCG, and 30% of CTG-treated animals. Posttreatment blood loss varied from an average of 64 mL/kg with CTG to 29 mL/kg with CEL, but no significant difference among groups was observed. CONCLUSION: These results suggest that the novel hemostatic devices perform at least as well as the current Committee on Tactical Combat Casualty Care standard for point-of-injury hemorrhage control. Despite their different compositions and sizes, the lack of clear superiority of any agent suggests that contemporary hemostatic dressing technology has potentially reached a plateau for efficacy. Copyright © 2013 Lippincott Williams & Wilkins.
Millenbaugh N.J.,Naval Medical Research Unit San Antonio |
Baskin J.B.,Naval Medical Research Unit San Antonio |
DeSilva M.N.,Naval Medical Research Unit San Antonio |
Elliott W.R.,Naval Medical Research Unit San Antonio |
Glickman R.D.,University of Texas Health Science Center at San Antonio
International Journal of Nanomedicine | Year: 2015
Purpose: The continued emergence of multidrug resistant bacterial infections and the decline in discovery of new antibiotics are major challenges for health care throughout the world. This situation has heightened the need for novel antimicrobial therapies as alternatives to traditional antibiotics. The combination of metallic nanoparticles and laser exposure has been proposed as a strategy to induce physical damage to bacteria, regardless of antibiotic sensitivity. The purpose of this study was to test the antibacterial effect of antibody-targeted gold nanoparticles combined with pulsed laser irradiation. Methods: Gold nanoparticles conjugated to antibodies specific to Staphylococcus aureuspeptidoglycan were incubated with suspensions of methicillin-resistant and methicillin-sensitive S. aureus (MRSA and MSSA). Bacterial suspensions were then exposed to 8 ns pulsed laser irradiation at a wavelength of 532 nm and fluences ranging from 1 to 5 J/cm2. Viability of the bacteria following laser exposure was determined using colony forming unit assays. Scanning electron microscopy was used to confirm the binding of nanoparticles to bacteria and the presence of cellular damage. Results: The laser-activated nanoparticle treatment reduced the surviving population to 31% of control in the MSSA population, while the survival in the MRSA population was reduced to 58% of control. Significant decreases in bacterial viability occurred when the laser fluence exceeded 1 J/cm2, and this effect was linear from 0 to 5 J/cm2 (r2=0.97). Significantly less bactericidal effect was observed for nonfunctionalized nanoparticles or functionalized nanoparticles without laser activation. Conclusion: Laser-activated nanoparticles targeted to S. aureus surface antigens significantly reduced the percentage of viable organisms and represents a promising new treatment modality that could be used either alone or as an adjunct to existing, conventional antibiotic therapy. © 2015 Millenbaugh et al.
Schultz S.,Naval Medical Research Unit San Antonio |
Desilva M.,Naval Medical Research Unit San Antonio |
Gu T.T.,University of Texas Health Science Center at San Antonio |
Qiang M.,University of Texas Health Science Center at San Antonio |
Whang K.,University of Texas Health Science Center at San Antonio
Basic and Clinical Pharmacology and Toxicology | Year: 2012
Acetaminophen has been used as an analgesic for more than a hundred years, but its mechanism of action has remained elusive. Recently, it has been shown that acetaminophen produces analgesia by the activation of the brain endocannabinoid receptor CB1 through its para-aminophenol (p-aminophenol) metabolite. The objective of this study was to determine whether p-aminophenol could be toxic for in vitro developing mouse cortical neurons as a first step in establishing a link between acetaminophen use and neuronal apoptosis. We exposed developing mouse cortical neurons to various concentrations of drugs for 24hr in vitro. Acetaminophen itself was not toxic to developing mouse cortical neurons at therapeutic concentrations of 10-250μg/ml. However, concentrations of p-aminophenol from 1 to 100μg/ml produced significant (p<0.05) loss of mouse cortical neuron viability at 24hr compared to the controls. The naturally occurring endocannabinoid anandamide also caused similar 24-hr loss of cell viability in developing mouse cortical neurons at concentrations from 1 to 100μg/ml, which indicates the mechanism of cell death could be through the cannabinoid receptors. The results of our experiments have shown a detrimental effect of the acetaminophen metabolite p-aminophenol on in vitro developing cortical neuron viability which could act through CB1 receptors of the endocannabinoid system. These results could be especially important in recommending an analgesic for children or individuals with traumatic brain injury who have developing cortical neurons. © 2011.
Hwang Y.Y.,Naval Medical Research Unit San Antonio |
Ramalingam K.,University of Texas Health Science Center at San Antonio |
Bienek D.R.,Naval Medical Research Unit San Antonio |
Lee V.,University of Texas Health Science Center at San Antonio |
And 2 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2013
Acinetobacter baumannii has emerged as a serious problematic pathogen due to the ever-increasing presence of antibiotic resistance, demonstrating a need for novel, broad-spectrum antimicrobial therapeutic options. Antimicrobial nanoemulsions are emulsified mixtures of detergent, oil, and water (droplet size, 100 to 800 nm) which have broad antimicrobial activity against bacteria, enveloped viruses, and fungi. Here, we screened the antimicrobial activities of five nanoemulsion preparations against four Acinetobacter baumannii isolates to identify the most suitable preparation for further evaluation. Among them, N5, which contains 10% (vol/vol) Triton X-100, 25% (vol/vol) soybean oil, and 1% (wt/vol) cetylpyridinium chloride (CPC), showed the best efficacy against A. baumannii in both its planktonic and biofilm forms and was selected for further study. Our data demonstrate that, while the killing of planktonic forms of A. baumannii was due to the 1% CPC component of our nanoemulsions, the breakdown of biofilms was achieved via the emulsified oil and detergent fractions. Furthermore, we documented the effect of ethanol and NaCl in combination with N5 on planktonic A. baumannii. In killing curves of N5 combined with other agents (ethanol or NaCl), a synergistic effect of a>2-log decrease in CFU/ml was observed. The antibiofilm activity of N5 was confirmed via a cell proliferation test and scanning electron microscopy. The effects of exposure to severe environmental conditions, which simulates the field conditions in Iraq and Afghanistan, were evaluated, and this exposure did not affect the overall antimicrobial activity of N5. These studies lay a solid foundation for the utilization of nanoemulsions against the antibiotic-resistant forms of A. baumannii. © 2013, American Society for Microbiology. All Rights Reserved.
Dobson G.P.,Institute of Tropical Medicine |
Letson H.L.,Institute of Tropical Medicine |
Sharma R.,Institute of Tropical Medicine |
Sheppard F.R.,Naval Medical Research Unit San Antonio |
Cap A.P.,U.S. Army
Journal of Trauma and Acute Care Surgery | Year: 2015
Traumatic-induced coagulopathy (TIC) is a hemostatic disorder that is associated with significant bleeding, transfusion requirements, morbidity and mortality. A disorder similar or analogous to TIC was reported around 70 years ago in patients with shock, hemorrhage, burns, cardiac arrest or undergoing major surgery, and the condition was referred to as a "severe bleeding tendency," "defibrination syndrome," "consumptive disorder," and later by surgeons treating US Vietnam combat casualties as a "diffuse oozing coagulopathy." In 1982, Moore's group termed it the "bloody vicious cycle," others "the lethal triad," and in 2003 Brohi and colleagues introduced "acute traumatic coagulopathy" (ATC). Since that time, early TIC has been cloaked in many names and acronyms, including a "fibrinolytic form of disseminated intravascular coagulopathy (DIC)." A global consensus on naming is urgently required to avoid confusion. In our view, TIC is a dynamic entity that evolves over time and no single hypothesis adequately explains the different manifestations of the coagulopathy. However, early TIC is not DIC because an increased thrombin-generating potential in vitro does not imply a clinically relevant thrombotic state in vivo as early TIC is characterized by excessive bleeding, not thrombosis. DIC with its diffuse anatomopathologic fibrin deposition appears to be a latter phase progression of TIC associated with unchecked inflammation and multiple organ dysfunction. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Colthirst P.M.,Institute of Surgical Research |
Berg R.G.,Institute of Surgical Research |
DeNicolo P.,Institute of Surgical Research |
Simecek J.W.,Naval Medical Research Unit San Antonio
Military Medicine | Year: 2013
The documentation of dental emergency (DE) rates in past global conflicts has been well established; however, little is known about wartime DE costs on the battlefield. Using DEs as an example for decreased combat effectiveness, this article analyzes the cost of treating DEs in theater, both in terms of fixed and variable costs, and also highlighted the difficulties that military units experience when faced with degradation of combat manpower because of DEs. The study found that Dental-Disease and Non-Battle Injury cost the U.S. Army a total of $21.4M between July 1, 2009 and June 30, 2010, and $21.9M between July 1, 2010 and June 30, 2011. The results also revealed that approximately 32% of DE required follow-up treatment over the 2-year period, which increased the costs associated with a DE over time. Understanding the etiology and cost of DE cases, military dental practitioners will be better equipped to provide oral health instructions and preventive measures before worldwide deploymen © Association of Military Surgeons of the U.S. All rights reserved.
Bienek D.R.,Naval Medical Research Unit San Antonio |
Bienek D.R.,University of Texas at San Antonio |
Perez N.M.,Naval Medical Research Unit San Antonio
Military Medicine | Year: 2013
The usability of a rapid point-of-care ABO-Rh blood typing kit was determined by comparing the performance of individuals with extensive medical training/experience to those with a lesser extent. Subjects were asked to use the blood typing kit with their own blood. These outcomes were compared to that listed in the subject's medical record, stamped on their dog tag, and the result interpreted by a laboratorian. For all participants, there was ~80% consistency between the result interpreted by the subject and that stated in their medical record. The participant's level of formal education (P ≤ 0.05) affected the accuracy of the blood typing kit. When comparing the subject's outcome to that stated in their medical record, the performance of individuals in the Medical Corps was approximately 10% and 25% higher (P < 0.05) than that observed with Hospital Corpsman or Medical Service Corps members, respectively. To remove bias that can occur when interpreting the blood type of oneself, the subjects also interpreted the result from cards prepared by the investigator. Taken together, a discrepancy between the potential diagnostic accuracy of the kit and that observed with potential end users was identified. © Association of Military Surgeons of the U.S. All rights reserved.
Vivekananda J.,Naval Medical Research Unit San Antonio |
Salgado C.,Naval Medical Research Unit San Antonio |
Millenbaugh N.J.,Naval Medical Research Unit San Antonio
Biochemical and Biophysical Research Communications | Year: 2014
Staphylococcus aureus is a versatile pathogen capable of causing a broad spectrum of diseases ranging from superficial skin infections to life threatening conditions such as endocarditis, septicemia, pneumonia and toxic shock syndrome. In vitro and in vivo studies identified an exotoxin, α-toxin, as a major cause of S. aureus toxicity. Because S. aureus has rapidly evolved resistance to a number of antibiotics, including methicillin, it is important to identify new therapeutic strategies, other than antibiotics, for inhibiting the harmful effects of this pathogen. Aptamers are single-stranded DNA or RNA oligonucleotides with three-dimensional folded conformations that bind with high affinity and selectivity to targets and modulate their biological functions. The goal of this study was to isolate DNA aptamers that specifically inhibit the cytotoxic activity of α-toxin. After 10 rounds of Systematic Evolution of Ligands by EXponential Enrichment (SELEX), 49 potential anti-α-toxin aptamers were identified. In vitro neutralization assays demonstrated that 4 of these 49 aptamers, AT-27, AT-33, AT-36, and AT-49, significantly inhibited α-toxin-mediated cell death in Jurkat T cells. Furthermore, RT-PCR analysis revealed that α-toxin increased the transcription of the inflammatory cytokines TNF-α and IL-17 and that anti-α-toxin aptamers AT-33 and AT-36 inhibited the upregulation of these genes. Collectively, the data suggest the feasibility of generating functionally effective aptamers against α-toxin for treatment of S. aureus infections. © 2014 Elsevier Inc. All rights reserved.
PubMed | Naval Medical Research Unit San Antonio
Type: | Journal: Infection and drug resistance | Year: 2016
Enzymatic debridement is a therapeutic strategy used clinically to remove necrotic tissue from wounds. Some of the enzymes utilized for debridement have been tested against bacterial pathogens, but the effectiveness of these agents in dispersing clinically relevant biofilms has not been fully characterized. Here, we developed an in vitro Staphylococcus aureus biofilm model that mimics wound-like conditions and employed this model to investigate the antibiofilm activity of four enzymatic compounds. Human plasma at concentrations of 0%-50% was supplemented into growth media and used to evaluate biofilm biomass accumulation over 24 hours and 48 hours in one methicillin-sensitive and five methicillin-resistant strains of S. aureus. Supplementation of media with 10% human plasma resulted in the most robust biofilms in all six strains. The enzymes -amylase, bromelain, lysostaphin, and papain were then tested against S. aureus biofilms cultured in 10% human plasma. Quantification of biofilms after 2 hours and 24 hours of treatment using the crystal violet assay revealed that lysostaphin decreased biomass by up to 76%, whereas -amylase, bromelain, and papain reduced biomass by up to 97%, 98%, and 98%, respectively. Scanning electron microscopy confirmed that the dispersal agents detached the biofilm exopolysaccharide matrix and bacteria from the growth surface. Lysostaphin caused less visible dispersal of the biofilms, but unlike the other enzymes, induced morphological changes indicative of bacterial cell damage. Overall, our results indicate that use of enzymes may be an effective means of eradicating biofilms and a promising strategy to improve treatment of multidrug-resistant bacterial infections.