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1.
Burns ; 48(8): 1825-1835, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35168858

RESUMEN

INTRODUCTION: Burn care is a relatively small, mutidisciplinary field with variability in practices between centers. Given these factors, survey studies are frequently used to better understand practice variations, establish guidelines, and direct future research. If survey research is poorly designed or reported, it limits the ability to form meaningful conclusions. This study evaluates the quality of survey studies published in burn care and determines areas of improvement to increase generalizability. METHODS: A systematic review was performed by two independent reviewers. Three databases (PubMed, Scopus, Web of Science) were queried between January 1, 2000 and March 19, 2020. Studies were included if they surveyed any member of the multidisciplinary burn team on a topic related to burn care, and surveys of non-clinicians were excluded. Data related to survey content, methodology, and quality was extracted for analysis. RESULTS: Of 247 citations, 144 met inclusion criteria. The number of published surveys increased by an average of 23% annually over the study period (p < 0.001). Studies represented a breadth of countries, scopes, themes, and disciplines. Few studies reported using reminders or incentives. The majority did not report survey development steps or validity/reliability, and half did not include the questionnaire in the publication. The median (IQR) response rate of all studies was 54% (32-83). A subgroup analysis of surveys to North American burn directors (N = 28) had a response rate of 40% (26-50). CONCLUSION: Survey reporting in the burn care literature is generally inconsistent, limiting the ability to apply this research into practice.


Asunto(s)
Quemaduras , Humanos , Reproducibilidad de los Resultados , Quemaduras/terapia , Encuestas y Cuestionarios , Informe de Investigación , Motivación
2.
Surg Infect (Larchmt) ; 22(10): 1047-1051, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34255574

RESUMEN

Background: Anastomotic leak is among the most dreaded complications in patients undergoing colorectal surgery. We have discovered that in rodents, collagenase-producing bacteria, particularly Enterococcus faecalis, promotes anastomotic leak by degrading healing anastomotic tissue. Yet, it is unclear if these organisms play a role in humans. Patients and Methods: Patients undergoing colorectal resection at the University of Chicago from July 2014 through June 2019 who developed a post-operative infection were stratified into infections that resulted from an anastomotic leak, a Hartmann pouch stump leak, or a deep infection without an associated staple line leak. Results: Forty-two patients had available culture data. Of these patients, 19 were found to have an anastomotic leak, 7 had a stump leak, and 16 had a deep infection that was not associated with a staple line. Enterococcus faecalis was identified in 24% of all infections and was associated with the development of anastomotic leak (p = 0.029). When the organisms were classified into their known ability to produce collagenase, 74% of patients with an anastomotic leak were colonized with collagenase-producing organisms, compared with only 28% of patients with a deep infection or stump leak (p = 0.022). Antibiotic-resistant organisms were more common in patients with anastomotic leak (p = 0.01). Conclusions: Collagenase-producing and antibiotic-resistant organisms are more prevalent in anastomotic leak infections compared with other deep or organ/space infections. This lends evidence to a bacterial driven pathogenesis of leak and suggests that targeting these organisms may be a novel strategy to reduce this complication.


Asunto(s)
Cirugía Colorrectal , Procedimientos Quirúrgicos del Sistema Digestivo , Anastomosis Quirúrgica/efectos adversos , Fuga Anastomótica/epidemiología , Enterococcus faecalis , Humanos
3.
Protein Expr Purif ; 187: 105932, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34214599

RESUMEN

Virus-like particles (VLPs) have the potential to be used as display platforms to develop vaccines against infectious and non-infectious agents. However, most VLPs used as vaccine display platforms are derived from viruses that infect humans; unfortunately, most humans already have pre-existing antibodies against these platforms and thus, the immunogenicity of these vaccines may be compromised. VLP platforms derived from viruses that infect bacteria (bacteriophages), especially bacteriophages that infect bacteria, which do not colonize humans are less likely to have pre-existing antibodies against the platforms in the human population. In this study, we assessed whether two putative coat proteins (ORF13 and ORF14) derived from a thermophilic bacteriophage (ΦIN93) can be expressed and purified from a mesophilic bacterium such as E. coli. We also assessed whether expressed coat proteins can assemble to form VLPs. Truncated versions of ORF13 and ORF14 were successfully co-expressed in bacteria; the co-expressed truncated proteins formed oval structures that look like VLPs, but their sizes were less than those of an authentic ΦIN93 virus.


Asunto(s)
Bacteriófagos/metabolismo , Proteínas de la Cápside/metabolismo , Vacunas de Partículas Similares a Virus/metabolismo , Virus/metabolismo , Secuencia de Aminoácidos , Anticuerpos Neutralizantes/química , Anticuerpos Neutralizantes/genética , Anticuerpos Neutralizantes/metabolismo , Infecciones Bacterianas/metabolismo , Proteínas de la Cápside/química , Proteínas de la Cápside/genética , Escherichia coli , Regulación de la Expresión Génica , Humanos , Unión Proteica , Vacunas de Partículas Similares a Virus/química , Virus/genética
4.
Opt Lett ; 45(22): 6258-6261, 2020 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-33186964

RESUMEN

Optical bandpass filters can be utilized to suppress parasitic broadband spectral power prior to laser amplification but are typically designed around specific frequencies or require manual adjustment, thus limiting their compatibility with highly tunable or integrated laser systems. In this Letter, we introduce a self-adaptive volume holographic filter using the dynamic two-beam coupling interaction in photorefractive BaTiO3, demonstrating -10dB suppression of amplified spontaneous emission noise surrounding a tunable 780 nm diode laser peak, with <2nm filter bandwidth and 50% power throughput. The spectral filtering is automatically centered on the lasing mode, with an estimated auto-tuning rate of 100 GHz/s under typical conditions. Furthermore, the filter suppression and bandwidth can be optimized via the two-beam coupling intensity ratio and angle, respectively, for versatile control over the self-adaptive filter characteristics.

5.
Cutan Ocul Toxicol ; 39(2): 143-157, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32321319

RESUMEN

Reactive Skin Decontamination Lotion (RSDL®) is an FDA-approved skin decontamination kit carried by service members for removal and neutralisation of vesicants and nerve agents. The RSDL kit, comprised of a lotion-impregnated sponge, was shown to be the superior medical decontamination device for chemical warfare agent (CWA) exposure on intact skin. In the event of a chemical exposure situation (i.e. terrorism, battlefield) physical injuries are probable, and preservation of life will outweigh the risk associated with application of RSDL to compromised skin. The purpose of this study was to quantify the rate and quality of wound healing in epidermal skin wounds treated with RSDL in a porcine model. Degree of wound healing was assessed using bioengineering methods to include ballistometry, colorimetry, evaporimetry, and high-frequency ultrasonography. Clinical observation, histopathology and immunohistochemistry were also utilised. All pigs received four bilateral superficial abdominal wounds via a pneumatic dermatome on their ventral abdomen, then were treated with the following dressings over a seven-day period: RSDL sponge, petroleum based Xeroform® gauze, 3 M™ Tegaderm™ Film, and 3 M™ Tegaderm™ Foam. Two additional non-wounded sites on the flank were used as controls. Two groups of pigs were then evaluated for a 21- or 56-day time period, representing short- and long-term wound-healing progression. Our findings indicated RSDL had a negative impact on wound-healing progression at both 21 and 56 days post-injury. Wounds receiving RSDL demonstrated a decreased skin elasticity, significant transepidermal water loss, and altered skin colouration and thickness. In addition, the rate of wound healing was delayed, and return to a functional skin barrier was altered when compared to non-RSDL-treated wounds. In conclusion, wound management care and clinical therapeutic intervention plans should be established to account for a prolonged duration of healing in patients with RSDL-contaminated wounds.


Asunto(s)
Descontaminación/métodos , Crema para la Piel/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Animales , Vendajes , Sustancias para la Guerra Química , Femenino , Modelos Animales , Piel/patología , Porcinos , Porcinos Enanos
6.
ACS Med Chem Lett ; 10(5): 761-766, 2019 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-31097996

RESUMEN

The threat of a deliberate release of chemical nerve agents has underscored the need to continually improve field effective treatments for these types of poisonings. The oxime containing HLö-7 is a potential second-generation therapeutic reactivator. A synthetic process for HLö-7 is detailed with improvements to the DIBAL reduction and ion exchange steps. HLö-7 was visualized for the first time within the active site of human acetylcholinesterase and its relative ex vivo potency confirmed against various nerve agents using a phrenic nerve hemidiaphragm assay.

7.
Antiviral Res ; 166: 56-65, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30926288

RESUMEN

Human papillomaviruses (HPVs) are the most common sexually transmitted infections. HPVs are transmitted through anogenital sex or oral sex. Anogenital transmission/infection is associated with anogenital cancers and genital warts while oral transmission/infection is associated with head and neck cancers (HNCs) including recurrent respiratory papillomatosis. Current HPV vaccines protect against HPV types associated with ∼90% of cervical cancers and are expected to protect against a percentage of HNCs. However, only a few studies have assessed the efficacy of current vaccines against oral HPV infections. We had previously developed a mixed MS2-L2 candidate HPV vaccine based on bacteriophage MS2 virus-like particles (VLPs). The mixed MS2-L2 VLPs consisted of a mixture of two MS2-L2 VLPs displaying: i) a concatemer of L2 peptide (epitope 20-31) from HPV31 & L2 peptide (epitope 17-31) from HPV16 and ii) a consensus L2 peptide representing epitope 69-86. The mixed MS2-L2 VLPs neutralized/protected mice against six HPV types associated with ∼87% of cervical cancer. Here, we show that the mixed MS2-L2 VLPs can protect mice against additional HPV types; at the genital region, the VLPs protect against HPV53, 56, 11 and at the oral region, the VLPs protect against HPV16, 35, 39, 52, and 58. Thus, mixed MS2-L2 VLPs protect against eleven oncogenic HPV types associated with ∼95% of cervical cancer. The VLPs also have the potential to protect, orally, against the same oncogenic HPVs, associated with ∼99% of HNCs, including HPV11, which is associated with up to 32% of recurrent respiratory papillomatosis. Moreover, mixed MS2-L2 VLPs are thermostable at room temperature for up to 60 days after spray-freeze drying and they are protective against oral HPV infection.


Asunto(s)
Protección Cruzada , Papillomaviridae/inmunología , Infecciones por Papillomavirus/prevención & control , Vacunas de Partículas Similares a Virus/inmunología , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales/inmunología , Proteínas de la Cápside/inmunología , Protección Cruzada/inmunología , Epítopos/inmunología , Femenino , Neoplasias de Cabeza y Cuello/etiología , Neoplasias de Cabeza y Cuello/prevención & control , Neoplasias de Cabeza y Cuello/virología , Humanos , Inmunización/métodos , Levivirus/inmunología , Ratones , Pruebas de Neutralización , Proteínas Oncogénicas Virales/inmunología , Vacunas contra Papillomavirus/inmunología , Infecciones del Sistema Respiratorio/prevención & control , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Vacunación/métodos
8.
Phys Rev Lett ; 120(26): 263201, 2018 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-30004774

RESUMEN

We experimentally demonstrate a shaken-lattice interferometer. Atoms are trapped in the ground Bloch state of a red-detuned optical lattice. Using a closed-loop optimization protocol based on the dcrab algorithm, we phase-modulate (shake) the lattice to transform the atom momentum state. In this way, we implement an atom beam splitter and build five interferometers of varying interrogation times T_{I}. The sensitivity of shaken-lattice interferometry is shown to scale as T_{I}^{2}, consistent with simulation (2C. A. Weidner, H. Yu, R. Kosloff, and D. Z. Anderson, Phys. Rev. A 95, 043624 (2017).PLRAAN2469-992610.1103/PhysRevA.95.043624). Finally, we show that we can measure the sign of an applied signal and optimize the interferometer in the presence of a bias signal.

9.
Am J Respir Cell Mol Biol ; 58(6): 696-705, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29314868

RESUMEN

Inhalation of powerful chemical agents, such as sulfur mustard (SM), can have debilitating pulmonary consequences, such as bronchiolitis obliterans (BO) and parenchymal fibrosis (PF). The underlying pathogenesis of disorders after SM inhalation is not clearly understood, resulting in a paucity of effective therapies. In this study, we evaluated the role of profibrotic pathways involving transforming growth factor-ß (TGF-ß) and platelet-derived growth factor (PDGF) in the development of BO and PF after SM inhalation injury using a rat model. Adult Sprague-Dawley rats were intubated and exposed to SM (1.0 mg/kg), then monitored daily for respiratory distress, oxygen saturation changes, and weight loss. Rats were killed at 7, 14, 21, or 28 days, and markers of injury were determined by histopathology; pulmonary function testing; and assessment of TGF-ß, PDGF, and PAI-1 concentrations. Respiratory distress developed over time after SM inhalation, with progressive hypoxemia, respiratory distress, and weight loss. Histopathology confirmed the presence of both BO and PF, and both gradually worsened with time. Pulmonary function testing demonstrated a time-dependent increase in lung resistance, as well as a decrease in lung compliance. Concentrations of TGF-ß, PDGF, and PAI-1 were elevated at 28 days in lung, BAL fluid, and/or plasma. Time-dependent development of BO and PF occurs in lungs of rats exposed to SM inhalation, and the elevated concentrations of TGF-ß, PDGF, and PAI-1 suggest involvement of these profibrotic pathways in the aberrant remodeling after injury.


Asunto(s)
Bronquiolitis Obliterante/inducido químicamente , Gas Mostaza/administración & dosificación , Gas Mostaza/toxicidad , Fibrosis Pulmonar/inducido químicamente , Administración por Inhalación , Animales , Bronquiolitis Obliterante/metabolismo , Bronquiolitis Obliterante/mortalidad , Bronquiolitis Obliterante/patología , Líquido del Lavado Bronquioalveolar , Sustancias para la Guerra Química/toxicidad , Relación Dosis-Respuesta a Droga , Inhibidor 1 de Activador Plasminogénico/metabolismo , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/mortalidad , Ratas Sprague-Dawley , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Pruebas de Función Respiratoria , Factor de Crecimiento Transformador beta1/metabolismo , Pérdida de Peso/efectos de los fármacos
10.
Dev Sci ; 21(3): e12561, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-28464381

RESUMEN

An individual's socioeconomic status (SES) is often viewed as a proxy for a host of environmental influences. SES disparities have been linked to variance in brain structures particularly the hippocampus, a neural substrate of learning and memory. However, it is unclear whether the association between SES and hippocampal volume is similar in children and adults. We investigated the relationship between hippocampal volume and SES in a group of children (n = 31, age 8-12 years) and a group of young adults (n = 32, age 18-25 years). SES was assessed with four indicators that loaded on a single factor, therefore a composite SES scores was used in the main analyses. Hippocampal volume was measured using manual demarcation on high resolution structural images. SES was associated with hippocampal volume in the children, but not in adults, suggesting that in childhood, but not adulthood, SES-related environmental factors influence hippocampal volume. In addition, hippocampal volume, but not SES, was associated with scores on a memory task, suggesting that net effects of postnatal environmental factors, captured by SES, are more distal determinants of memory performance than hippocampal volume. Longitudinal investigation of the association between SES, hippocampal volume and cognitive functioning may further our understanding of the putative neural mechanisms underlying SES-related environmental effects on cognitive development.


Asunto(s)
Hipocampo/fisiología , Memoria/fisiología , Tamaño de los Órganos/fisiología , Clase Social , Adolescente , Adulto , Aptitud/fisiología , Niño , Cognición/fisiología , Femenino , Humanos , Masculino , Estrés Psicológico , Adulto Joven
11.
Toxicol Sci ; 159(2): 461-469, 2017 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-28962529

RESUMEN

Sulfur mustard (SM) is a chemical warfare agent. When inhaled, SM causes significant injury to the respiratory tract. Although the mechanism involved in acute airway injury after SM inhalation has been well described previously, the mechanism of SM's contribution to distal lung vascular injury is not well understood. We hypothesized that acute inhalation of vaporized SM causes activated systemic coagulation with subsequent pulmonary vascular thrombi formation after SM inhalation exposure. Sprague Dawley rats inhaled SM ethanolic vapor (3.8 mg/kg). Barium/gelatin CT pulmonary angiograms were performed to assess for pulmonary vascular thrombi burden. Lung immunohistochemistry was performed for common procoagulant markers including fibrin(ogen), von Willebrand factor, and CD42d in control and SM-exposed lungs. Additionally, systemic levels of d-dimer and platelet aggregometry after adenosine diphosphate- and thrombin-stimulation were measured in plasma after SM exposure. In SM-exposed lungs, chest CT angiography demonstrated a significant decrease in the distal pulmonary vessel density assessed at 6 h postexposure. Immunohistochemistry also demonstrated increased intravascular fibrin(ogen), vascular von Willebrand factor, and platelet CD42d in the distal pulmonary vessels (<200 µm diameter). Circulating d-dimer levels were significantly increased (p < .001) at 6, 9, and 12 h after SM inhalation versus controls. Platelet aggregation was also increased in both adenosine diphosphate - (p < .01) and thrombin- (p < .001) stimulated platelet-rich plasma after SM inhalation. Significant pulmonary vascular thrombi formation was evident in distal pulmonary arterioles following SM inhalation in rats assessed by CT angiography and immunohistochemistry. Enhanced systemic platelet aggregation and activated systemic coagulation with subsequent thrombi formation likely contributed to pulmonary vessel occlusion.


Asunto(s)
Arteriolas/efectos de los fármacos , Sustancias para la Guerra Química/toxicidad , Pulmón/efectos de los fármacos , Gas Mostaza/toxicidad , Trombosis/inducido químicamente , Animales , Arteriolas/patología , Angiografía por Tomografía Computarizada , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Exposición por Inhalación , Pulmón/irrigación sanguínea , Enfermedades Pulmonares/inducido químicamente , Masculino , Gas Mostaza/administración & dosificación , Agregación Plaquetaria/efectos de los fármacos , Ratas , Ratas Sprague-Dawley
12.
Toxicol Sci ; 154(2): 341-353, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27605419

RESUMEN

Sulfur mustard (bis 2-chloroethyl ethyl sulfide, SM) is a powerful bi-functional vesicating chemical warfare agent. SM tissue injury is partially mediated by the overproduction of reactive oxygen species resulting in oxidative stress. We hypothesized that using a catalytic antioxidant (AEOL 10150) to alleviate oxidative stress and secondary inflammation following exposure to SM would attenuate the toxic effects of SM inhalation. Adult male rats were intubated and exposed to SM (1.4 mg/kg), a dose that produces an LD50 at approximately 24 h. Rats were randomized and treated via subcutaneous injection with either sterile PBS or AEOL 10150 (5 mg/kg, sc, every 4 h) beginning 1 h post-SM exposure. Rats were euthanized between 6 and 48 h after exposure to SM and survival and markers of injury were determined. Catalytic antioxidant treatment improved survival after SM inhalation in a dose-dependent manner, up to 52% over SM PBS at 48 h post-exposure. This improvement was sustained for at least 72 h after SM exposure when treatments were stopped after 48 h. Non-invasive monitoring throughout the duration of the studies also revealed blood oxygen saturations were improved by 10% and clinical scores were reduced by 57% after SM exposure in the catalytic antioxidant treatment group. Tissue analysis showed catalytic antioxidant therapy was able to decrease airway cast formation by 69% at 48 h post-exposure. To investigate antioxidant induced changes at the peak of injury, several biomarkers of oxidative stress and inflammation were evaluated at 24 h post-exposure. AEOL 10150 attenuated SM-mediated lung lipid oxidation, nitrosative stress and many proinflammatory cytokines. The findings indicate that catalytic antioxidants may be useful medical countermeasure against inhaled SM exposure.


Asunto(s)
Antídotos/farmacología , Antioxidantes/farmacología , Sustancias para la Guerra Química/toxicidad , Lesión Pulmonar/prevención & control , Pulmón/efectos de los fármacos , Metaloporfirinas/farmacología , Gas Mostaza/toxicidad , Estrés Oxidativo/efectos de los fármacos , Neumonía/prevención & control , Animales , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Mediadores de Inflamación/metabolismo , Exposición por Inhalación , Pulmón/metabolismo , Pulmón/patología , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/metabolismo , Lesión Pulmonar/patología , Masculino , Neumonía/inducido químicamente , Neumonía/metabolismo , Neumonía/patología , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Factores de Tiempo
13.
Risk Anal ; 36(2): 378-95, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26249655

RESUMEN

In this article, we develop statistical models to predict the number and geographic distribution of fires caused by earthquake ground motion and tsunami inundation in Japan. Using new, uniquely large, and consistent data sets from the 2011 Tohoku earthquake and tsunami, we fitted three types of models-generalized linear models (GLMs), generalized additive models (GAMs), and boosted regression trees (BRTs). This is the first time the latter two have been used in this application. A simple conceptual framework guided identification of candidate covariates. Models were then compared based on their out-of-sample predictive power, goodness of fit to the data, ease of implementation, and relative importance of the framework concepts. For the ground motion data set, we recommend a Poisson GAM; for the tsunami data set, a negative binomial (NB) GLM or NB GAM. The best models generate out-of-sample predictions of the total number of ignitions in the region within one or two. Prefecture-level prediction errors average approximately three. All models demonstrate predictive power far superior to four from the literature that were also tested. A nonlinear relationship is apparent between ignitions and ground motion, so for GLMs, which assume a linear response-covariate relationship, instrumental intensity was the preferred ground motion covariate because it captures part of that nonlinearity. Measures of commercial exposure were preferred over measures of residential exposure for both ground motion and tsunami ignition models. This may vary in other regions, but nevertheless highlights the value of testing alternative measures for each concept. Models with the best predictive power included two or three covariates.


Asunto(s)
Terremotos , Incendios , Medición de Riesgo/métodos , Tsunamis , Algoritmos , Planificación en Desastres/métodos , Monitoreo del Ambiente/métodos , Geografía , Japón , Modelos Lineales , Distribución de Poisson , Valor Predictivo de las Pruebas , Análisis de Regresión , Reproducibilidad de los Resultados
14.
Toxicol Lett ; 244: 21-27, 2016 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-26562769

RESUMEN

Phosgene (CG), a toxic inhalation and industrial hazard, causes bronchoconstriction, vasoconstriction and associated pathological effects that could be life threatening. Ion channels of the transient receptor potential (TRP) family have been identified to act as specific chemosensory molecules in the respiratory tract in the detection, control of adaptive responses and initiation of detrimental signaling cascades upon exposure to various toxic inhalation hazards (TIH); their activation due to TIH exposure may result in broncho- and vasoconstriction. We studied changes in the regulation of intracellular free Ca(2+) concentration ([Ca(2+)]i) in cultures of human bronchial smooth muscle cells (BSMC) and human pulmonary microvascular endothelial cells (HPMEC) exposed to CG (16ppm, 8min), using an air/liquid interface exposure system. CG increased [Ca(2+)]i (p<0.05) in both cell types, The CG-induced [Ca(2+)]i was blocked (p<0.05) by two types of TRP channel blockers, SKF-96365, a general TRP channel blocker, and RR, a general TRPV (vanilloid type) blocker, in both BSMC and HPMEC. These effects correlate with the in vivo efficacies of these compounds to protect against lung injury and 24h lethality from whole body CG inhalation exposure in mice (8-10ppm×20min). Thus the TRP channel mechanism appears to be a potential target for intervention in CG toxicity.


Asunto(s)
Antídotos/farmacología , Bronquios/efectos de los fármacos , Sustancias para la Guerra Química/toxicidad , Células Endoteliales/efectos de los fármacos , Moduladores del Transporte de Membrana/farmacología , Miocitos del Músculo Liso/efectos de los fármacos , Fosgeno/toxicidad , Canales de Potencial de Receptor Transitorio/antagonistas & inhibidores , Animales , Bronquios/metabolismo , Bronquios/patología , Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Células Cultivadas , Células Endoteliales/metabolismo , Células Endoteliales/patología , Humanos , Imidazoles/farmacología , Exposición por Inhalación , Masculino , Ratones , Terapia Molecular Dirigida , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Canales de Potencial de Receptor Transitorio/agonistas , Canales de Potencial de Receptor Transitorio/metabolismo
15.
Toxicol Lett ; 244: 8-20, 2016 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-26562770

RESUMEN

Toxic industrial chemicals are used throughout the world to produce everyday products such as household and commercial cleaners, disinfectants, pesticides, pharmaceuticals, plastics, paper, and fertilizers. These chemicals are produced, stored, and transported in large quantities, which poses a threat to the local civilian population in cases of accidental or intentional release. Several of these chemicals have no known medical countermeasures for their toxic effects. Phosgene is a highly toxic industrial chemical which was used as a chemical warfare agent in WWI. Exposure to phosgene causes latent, non-cardiogenic pulmonary edema which can result in respiratory failure and death. The mechanisms of phosgene-induced pulmonary injury are not fully identified, and currently there is no efficacious countermeasure. Here, we provide a proposed mechanism of phosgene-induced lung injury based on the literature and from studies conducted in our lab, as well as provide results from studies designed to evaluate survival efficacy of potential therapies following whole-body phosgene exposure in mice. Several therapies were able to significantly increase 24h survival following an LCt50-70 exposure to phosgene; however, no treatment was able to fully protect against phosgene-induced mortality. These studies provide evidence that mortality following phosgene toxicity can be mitigated by neuro- and calcium-regulators, antioxidants, phosphodiesterase and endothelin receptor antagonists, angiotensin converting enzymes, and transient receptor potential cation channel inhibitors. However, because the mechanism of phosgene toxicity is multifaceted, we conclude that a single therapeutic is unlikely to be sufficient to ameliorate the multitude of direct and secondary toxic effects caused by phosgene inhalation.


Asunto(s)
Antídotos/uso terapéutico , Sustancias para la Guerra Química , Lesión Pulmonar/tratamiento farmacológico , Pulmón/efectos de los fármacos , Fosgeno , Animales , Modelos Animales de Enfermedad , Exposición por Inhalación , Pulmón/metabolismo , Pulmón/patología , Pulmón/fisiopatología , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/diagnóstico , Lesión Pulmonar/metabolismo , Lesión Pulmonar/fisiopatología , Masculino , Ratones , Terapia Molecular Dirigida , Transducción de Señal/efectos de los fármacos
16.
Rev Sci Instrum ; 87(12): 123108, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28040917

RESUMEN

We describe a system for loading a single atom from a reservoir into a blue-detuned crossed vortex bottle beam trap using a dynamic 1D optical lattice. The lattice beams are frequency chirped using acousto-optic modulators, which causes the lattice to move along its axial direction and behave like an optical conveyor belt. A stationary lattice is initially loaded with approximately 6000 atoms from a reservoir, and the conveyor belt transports them 1.1 mm from the reservoir to a bottle beam trap, where a single atom is loaded via light-assisted collisions. Photon counting data confirm that an atom can be delivered and loaded into the bottle beam trap 13.1% of the time.

17.
Opt Lett ; 40(14): 3368-71, 2015 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-26176471

RESUMEN

An atom-chip-based integrated optical lattice system for cold and ultracold atom applications is presented. The retroreflection optics necessary for forming the lattice are bonded directly to the atom chip, enabling a compact and robust on-chip optical lattice system. After achieving Bose-Einstein condensation in a magnetic chip trap, we load atoms directly into a vertically oriented 1D optical lattice and demonstrate Landau-Zener tunneling. The atom chip technology presented here can be readily extended to higher dimensional optical lattices.

18.
Toxicol Sci ; 143(1): 178-84, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25331496

RESUMEN

RATIONALE: Sulfur mustard (SM) is a chemical weapon stockpiled today in volatile regions of the world. SM inhalation causes a life-threatening airway injury characterized by airway obstruction from fibrin casts, which can lead to respiratory failure and death. Mortality in those requiring intubation is more than 80%. No therapy exists to prevent mortality after SM exposure. Our previous work using the less toxic analog of SM, 2-chloroethyl ethyl sulfide, identified tissue plasminogen activator (tPA) an effective rescue therapy for airway cast obstruction (Veress, L. A., Hendry-Hofer, T. B., Loader, J. E., Rioux, J. S., Garlick, R. B., and White, C. W. (2013). Tissue plasminogen activator prevents mortality from sulfur mustard analog-induced airway obstruction. Am. J. Respir. Cell Mol. Biol. 48, 439-447). It is not known if exposure to neat SM vapor, the primary agent used in chemical warfare, will also cause death due to airway casts, and if tPA could be used to improve outcome. METHODS: Adult rats were exposed to SM, and when oxygen saturation reached less than 85% (median: 6.5 h), intratracheal tPA or placebo was given under isoflurane anesthesia every 4 h for 48 h. Oxygen saturation, clinical distress, and arterial blood gases were assessed. Microdissection was done to assess airway obstruction by casts. RESULTS: Intratracheal tPA treatment eliminated mortality (0% at 48 h) and greatly improved morbidity after lethal SM inhalation (100% death in controls). tPA normalized SM-associated hypoxemia, hypercarbia, and lactic acidosis, and improved respiratory distress. Moreover, tPA treatment resulted in greatly diminished airway casts, preventing respiratory failure from airway obstruction. CONCLUSIONS: tPA given via airway more than 6 h after exposure prevented death from lethal SM inhalation, and normalized oxygenation and ventilation defects, thereby rescuing from respiratory distress and failure. Intra-airway tPA should be considered as a life-saving rescue therapy after a significant SM inhalation exposure incident.


Asunto(s)
Obstrucción de las Vías Aéreas/tratamiento farmacológico , Sustancias para la Guerra Química , Fibrinolíticos/administración & dosificación , Exposición por Inhalación , Pulmón/efectos de los fármacos , Gas Mostaza , Insuficiencia Respiratoria/prevención & control , Terapia Trombolítica , Activador de Tejido Plasminógeno/administración & dosificación , Acidosis/inducido químicamente , Acidosis/prevención & control , Administración por Inhalación , Obstrucción de las Vías Aéreas/inducido químicamente , Obstrucción de las Vías Aéreas/patología , Obstrucción de las Vías Aéreas/fisiopatología , Animales , Modelos Animales de Enfermedad , Esquema de Medicación , Pulmón/patología , Pulmón/fisiopatología , Masculino , Oxígeno/sangre , Ventilación Pulmonar/efectos de los fármacos , Ratas Sprague-Dawley , Respiración/efectos de los fármacos , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/patología , Insuficiencia Respiratoria/fisiopatología , Factores de Tiempo
19.
Int J Toxicol ; 33(4): 271-281, 2014 07.
Artículo en Inglés | MEDLINE | ID: mdl-24801489

RESUMEN

Mustard gas (sulfur mustard [SM], bis-[2-chloroethyl] sulfide) is a vesicating chemical warfare agent and a potential chemical terrorism agent. Exposure of SM causes debilitating skin blisters (vesication) and injury to the eyes and the respiratory tract; of these, the respiratory injury, if severe, may even be fatal. Therefore, developing an effective therapeutic strategy to protect against SM-induced respiratory injury is an urgent priority of not only the US military but also the civilian antiterrorism agencies, for example, the Homeland Security. Toward developing a respiratory medical countermeasure for SM, four different classes of therapeutic compounds have been evaluated in the past: anti-inflammatory compounds, antioxidants, protease inhibitors and antiapoptotic compounds. This review examines all of these different options; however, it suggests that preventing cell death by inhibiting apoptosis seems to be a compelling strategy but possibly dependent on adjunct therapies using the other drugs, that is, anti-inflammatory, antioxidant, and protease inhibitor compounds.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Antioxidantes/uso terapéutico , Sustancias para la Guerra Química/toxicidad , Intoxicación por Gas/tratamiento farmacológico , Modelos Biológicos , Gas Mostaza/toxicidad , Inhibidores de Proteasas/uso terapéutico , Animales , Antídotos/uso terapéutico , Apoptosis/efectos de los fármacos , Quimioterapia Combinada , Intoxicación por Gas/inmunología , Intoxicación por Gas/metabolismo , Intoxicación por Gas/patología , Humanos , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/patología , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/patología
20.
Bipolar Disord ; 15(6): 680-93, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23796123

RESUMEN

OBJECTIVES: Schizophrenia and bipolar disorder may share common neurobiological mechanisms, but few studies have directly compared gray and white matter structure in these disorders. We used diffusion-weighted magnetic resonance imaging and a region of interest based analysis to identify overlapping and distinct gray and white matter abnormalities in 35 patients with schizophrenia and 20 patients with bipolar I disorder in comparison to 56 healthy volunteers. METHODS: We examined fractional anisotropy within the white matter and mean diffusivity within the gray matter in 42 regions of interest defined on a probabilistic atlas following non-linear registration of the images to atlas space. RESULTS: Patients with schizophrenia had significantly lower fractional anisotropy in temporal (superior temporal and parahippocampal) and occipital (superior and middle occipital) white matter compared to patients with bipolar disorder and healthy volunteers. By contrast, both patient groups demonstrated significantly higher mean diffusivity in frontal (inferior frontal and lateral orbitofrontal) and temporal (superior temporal and parahippocampal) gray matter compared to healthy volunteers, but did not differ from each other. CONCLUSIONS: Our study implicates overlapping gray matter frontal and temporal lobe structural alterations in the neurobiology of schizophrenia and bipolar I disorder, but suggests that temporal and occipital lobe white matter deficits may be an additional risk factor for schizophrenia. Our findings may have relevance for future diagnostic classification systems and the identification of susceptibility genes for these disorders.


Asunto(s)
Trastorno Bipolar/patología , Corteza Cerebral/patología , Fibras Nerviosas Mielínicas/patología , Esquizofrenia/patología , Adulto , Factores de Edad , Análisis de Varianza , Anisotropía , Mapeo Encefálico , Imagen de Difusión por Resonancia Magnética , Femenino , Lateralidad Funcional , Humanos , Masculino , Probabilidad , Factores Sexuales , Adulto Joven
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