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1.
J Surg Res ; 286: 110-117, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36804690

RESUMEN

INTRODUCTION: Effective initial fluid resuscitation is the cornerstone intervention in the setting of severe burn injury. Critically, few major advances in burn resuscitation have been made since the 1970s, and since that time there has been only modest improvement in overall morbidity and mortality. Recently, investigations regarding the dynamic changes of vascular endothelium, and more specifically the vascular endothelial glycocalyx, in the setting of severe burn injury and resuscitation have offered insight into the possibility of more tightly controlling fluid shifts and understanding the consequences thereof during this critical period. METHODS: We conducted a literature search of the PubMed database using the terms "burn", and "glycocalyx" limited to studies published in the English language over the past 10 y. A total of 31 articles were initially identified. Abstracts and full text were manually reviewed to identify suitable articles. Of the identified articles, 10 were deemed relevant and included within this review, along with additional articles necessary to provide background on glycocalyx structure and function as well as principles of burn injury management. RESULTS: Glycocalyx shedding is a process known to occur early in the setting of severe burn injury and resuscitation. The degree of shedding tends to increase with age and severity of injury. Though the role and regulation of this shedding is incompletely understood, it has direct consequences on vascular unction and permeability and likely coagulation as well. CONCLUSIONS: Here in this research review, we examine what is known regarding the dynamic breakdown and reconstitution of the glycocalyx during burn injury and how it may be impacted by fluid resuscitation strategies. We further explore the need to more completely understand this mechanism and the consequences of its manipulation.


Asunto(s)
Quemaduras , Humanos , Quemaduras/terapia , Quemaduras/metabolismo , Endotelio Vascular/metabolismo , Fluidoterapia , Glicocálix/fisiología , Resucitación
2.
Acta Haematol ; 144(6): 633-640, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34237720

RESUMEN

INTRODUCTION: Viscoelastic coagulation tests are useful to assess coagulation status in the clinical setting and to aid in understanding underlying pathophysiological mechanisms that affect coagulation status. Such tests also are useful for coagulation research. Because mouse models are widely used to study molecular mechanisms in fine detail, a simple viscoelastic coagulation test requiring small blood volumes would be convenient for such studies in mice. METHODS: We tested viscoelastic coagulation properties of normal healthy adult mice using a novel veterinary clinical point-of-care device, Viscoelastic Coagulation Monitor (VCM Vet™; Entegrion Corp.). Fresh whole blood was collected from 63 healthy mature adult C57 black 6N mice, with ultimately 54 mice, equal numbers of male and females, used to determine reference intervals (RIs) for VCM test parameters. RESULTS: RIs were determined for equal numbers of male and female mice: clot time: 43.0-353.0 s; clot formation time: 49.4-137.6 s; alpha angle: 54.4-62.2°; A10: 25.0-49.6 VCM units; A20: 31.0-56.5 VCM units; maximum clot firmness: 37.6-62.8 VCM units; Lysis Index 30 (Li30): 99.8-100.0%; and Li45: 99.7-100.0%. Significant differences were found between male and female subgroups, where females had higher mean A10 and A20 and median MCF values, indicating greater clot firmness in female versus male mice. CONCLUSION: VCM Vet is a feasible viscoelastic coagulation test device for studies with mature adult mice, including studying inherent sex differences in coagulation parameters. Inherent differences in coagulability of male and female mice warrant further investigation to determine if such differences underlie greater coagulopathic, hemorrhagic, or thromboembolic risk during trauma or other pathophysiologic conditions.


Asunto(s)
Pruebas de Coagulación Sanguínea/normas , Animales , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea/métodos , Pruebas de Coagulación Sanguínea/veterinaria , Femenino , Cinética , Masculino , Ratones , Ratones Endogámicos C57BL , Valores de Referencia , Caracteres Sexuales
3.
Surg Open Sci ; 18: 91-92, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38435486

RESUMEN

The COVID-19 pandemic has exposed some of our best and worst qualities as a country. This commentary on "Domestic Firearm Violence Against Women (2018-2021)" discusses weaknesses in federal legislation and proposes ways for states to fill these gaps.

4.
Bioact Mater ; 28: 467-479, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37408799

RESUMEN

Implantable vascular devices are widely used in clinical treatments for various vascular diseases. However, current approved clinical implantable vascular devices generally have high failure rates primarily due to their surface lacking inherent functional endothelium. Here, inspired by the pathological mechanisms of vascular device failure and physiological functions of native endothelium, we developed a new generation of bioactive parylene (poly(p-xylylene))-based conformal coating to address these challenges of the vascular devices. This coating used a polyethylene glycol (PEG) linker to introduce an endothelial progenitor cell (EPC) specific binding ligand LXW7 (cGRGDdvc) onto the vascular devices for preventing platelet adhesion and selectively capturing endogenous EPCs. Also, we confirmed the long-term stability and function of this coating in human serum. Using two vascular disease-related large animal models, a porcine carotid artery interposition model and a porcine carotid artery-jugular vein arteriovenous graft model, we demonstrated that this coating enabled rapid generation of self-renewable "living" endothelium on the blood contacting surface of the expanded polytetrafluoroethylene (ePTFE) grafts after implantation. We expect this easy-to-apply conformal coating will present a promising avenue to engineer surface properties of "off-the-shelf" implantable vascular devices for long-lasting performance in the clinical settings.

5.
J Trauma Acute Care Surg ; 90(6): 1032-1039, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34016926

RESUMEN

INTRODUCTION: Previously, in a murine model of blunt thoracic trauma, we provided evidence of primary pulmonary thrombosis associated with increased expression of the cell adhesion molecule, P-selectin. In this study, mice are treated with P-selectin blocking antibody after injury to investigate the clinical viability of this antibody for the prevention of pulmonary thrombosis. In addition, viscoelastic testing is performed to investigate if P-selectin inhibition has a detrimental impact on normal hemostasis. METHODS: A murine model of thoracic trauma was used. Mice were divided into sham control and experimental injury groups. Thirty minutes after trauma, mice were treated with the following: P-selectin blocking antibody, isotype control antibody, low-dose heparin, high-dose heparin, or normal saline. At 90 minutes, whole blood was collected for characterization of coagulation by viscoelastic coagulation monitor (VCM Vet; Entegrion, Durham, NC). Mean clotting time, clot formation time, clot kinetics (α angle), and maximum clot firmness were compared between each treatment group. RESULTS: Mice that received P-selectin antibody 30 minutes after blunt thoracic trauma had four- to fivefold less (p < 0.001) arterial fibrin accumulation than those that received the isotype control. In both sham and trauma groups, compared with vehicle (normal saline) alone, no statistical difference was noted in any coagulation parameters after injection with P-selectin antibody, isotype control, or low-dose heparin. In addition, blinded histopathological evaluation yielded no difference in hemorrhage scores between injured mice treated with P-selectin blocking antibody and those treated with isotype antibody control. CONCLUSION: This study supports the clinical use of P-selectin blocking antibody for the prevention of pulmonary thrombosis by confirming its efficacy when given after a blunt thoracic trauma. In addition, we demonstrated that the administration of P-selectin antibody does not adversely affect systemic coagulation as measured by viscoelastic testing, suggesting that P-selectin antibody can be safely given during the acute posttraumatic period.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Selectina-P/antagonistas & inhibidores , Embolia Pulmonar/prevención & control , Traumatismos Torácicos/complicaciones , Heridas no Penetrantes/complicaciones , Animales , Coagulación Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Heparina/administración & dosificación , Humanos , Masculino , Ratones , Embolia Pulmonar/sangre , Embolia Pulmonar/etiología , Traumatismos Torácicos/sangre , Traumatismos Torácicos/terapia , Heridas no Penetrantes/sangre , Heridas no Penetrantes/terapia
6.
J Trauma Acute Care Surg ; 86(4): 583-591, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30562326

RESUMEN

BACKGROUND: Thromboembolic events within the pulmonary arterial vasculature are a troublesome complication of severe blunt thoracic trauma. Mechanisms underlying these events are currently in question as pulmonary thromboembolic events in this particular trauma population tend to be diagnosed more rapidly, more frequently and without an associated systemic thrombosis. This study investigates the role of P-selectin in thrombus formation through the use of in vivo blocking antibodies. We hypothesize that P-selectin plays a pivotal role in de novo pulmonary arterial thrombosis following blunt thoracic trauma. METHODS: A murine weight-drop model of lateral blunt thoracic trauma was used. Wild-type mice in the experimental group were given blocking antibodies against P-selectin prior to the trauma. All mice were euthanized at 24 hours for evaluation with hematoxylin-eosin staining or immunofluorescent staining for fibrin and P-selectin. RESULTS: Injured mice that did not receive the P-selectin antibody showed a robust fourfold to fivefold increase in fibrin accumulation in both coup and contrecoup tissues (fluorescence per um of arterial wall) compared to uninjured sham mice. In contrast, mice pretreated with P-selectin blocking antibody showed no significant increase in fibrin accumulation on either side of the lungs after blunt thoracic trauma. No difference in mean fibrin deposition was found between sham controls that received the P-selectin-blocking antibody and those that received an isotype control antibody. CONCLUSION: P-selectin expression increases at the pulmonary arterial luminal surface following blunt thoracic trauma. In addition, P-selectin-blocking in vivo prevents pulmonary arterial fibrin accumulation after blunt thoracic trauma, confirming that P-selectin is necessary for de novo pulmonary arterial thrombosis after traumatic injury.


Asunto(s)
Selectina-P/fisiología , Embolia Pulmonar/fisiopatología , Heridas no Penetrantes/fisiopatología , Animales , Anticuerpos Bloqueadores , Modelos Animales de Enfermedad , Ratones , Selectina-P/inmunología
7.
Shock ; 50(6): 696-705, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29394242

RESUMEN

Pulmonary thromboembolic events cause significant morbidity and mortality after severe trauma. Clinically, these lesions are believed to be emboli arising secondary to deep venous thrombosis (DVT) in the lower extremities. Recently, this notion has been challenged by clinical studies, showing that pulmonary clots arise after trauma in the absence of DVT. This suggests that pulmonary blood clots arise in situ via de novo thrombosis. In the present study, we characterize a murine weight-drop model of lateral blunt thoracic trauma. Our model demonstrates severe unilateral lung contusion injury with low (10%) mortality in the absence of extrapulmonary injury, after impact with a 50-g weight dropped from 45 cm height (657 J/m). At 24 h after injury, immunofluorescence and histological evidence revealed early pulmonary arterial thrombosis in the form of eccentric accumulation of fibrin and CD41 positive eosinophilic proteinaceous material, on both coup and contrecoup lung lobes of injured mice, indicating early thrombotic events both within and outside of the area of primary lung injury. Our model is ideal in that lateral impact enables greater impact energy to be applied to achieve significant lung contusion without significant mortality or extrapulmonary injury, and the model has additional translational value in creating thrombosis analogous to pulmonary embolism observed clinically after blunt thoracic trauma. To our knowledge, this is the first demonstration of de novo pulmonary thrombosis in a clinically translational model of blunt thoracic trauma, and supports challenges to current assumptions about the origin of pulmonary blood clots in the wake of severe traumatic injury.


Asunto(s)
Traumatismos Torácicos/metabolismo , Trombosis de la Vena/metabolismo , Animales , Lavado Broncoalveolar , Modelos Animales de Enfermedad , Fibrina/metabolismo , Técnica del Anticuerpo Fluorescente , Etiquetado Corte-Fin in Situ , Masculino , Ratones , Ratones Endogámicos C57BL , Glicoproteína IIb de Membrana Plaquetaria/metabolismo , Embolia Pulmonar/metabolismo
8.
Immunobiology ; 222(2): 188-197, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27720434

RESUMEN

Recent studies show a substantial incidence of Pneumocystis jirovecii colonization and infection in patients with chronic inflammatory lung conditions. However, little is known about the impact of Pneumocystis upon the regulation of pulmonary immunity. We demonstrate here that Pneumocystis polarizes macrophages towards an alternatively activated macrophage-like phenotype. Genetically engineered mice that lack the ability to signal through IL-4 and IL-13 were used to show that Pneumocystis alternative macrophage activation is dependent upon signaling through these cytokines. To determine whether Pneumocystis-induced macrophage polarization would impact subsequent immune responses, we infected mice with Pneumocystis and then challenged them with Pseudomonas aeruginosa 14 days later. In co-infected animals, a higher proportion of macrophages in the alveolar and interstitial spaces expressed both classical and alternatively activated markers and produced the regulatory cytokines TGFß and IL-10, as well as higher arginase levels than in mice infected with P. aeruginosa alone. Our results suggest that Pneumocystis reprograms the overall macrophage repertoire in the lung to that of a more alternatively-activated setpoint, thereby altering subsequent immune responses. These data may help to explain the association between Pneumocystis infection and decline in pulmonary function.


Asunto(s)
Macrófagos Alveolares/inmunología , Macrófagos Alveolares/metabolismo , Infecciones por Pneumocystis/inmunología , Infecciones por Pneumocystis/metabolismo , Animales , Biomarcadores , Citocinas/metabolismo , Modelos Animales de Enfermedad , Inmunofenotipificación , Activación de Macrófagos/inmunología , Ratones , Ratones Noqueados , Fenotipo , Infecciones por Pneumocystis/genética , Infecciones por Pneumocystis/microbiología , Pneumocystis carinii/inmunología , Neumonía Bacteriana/genética , Neumonía Bacteriana/inmunología , Neumonía Bacteriana/metabolismo , Neumonía Bacteriana/microbiología , Receptores de Superficie Celular/deficiencia , Receptores de Superficie Celular/genética
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