RESUMO
BACKGROUND: Inadequate activation of the innate immune system after trauma can lead to severe complications such as Acute Respiratory Distress Syndrome and Multiple Organ Dysfunction Syndrome. The spleen is thought to modulate the cellular immune system. Furthermore, splenectomy is associated with improved outcome in severely injured trauma patients. We hypothesized that a splenectomy alters the cellular immune response in polytrauma. METHODS: All adult patients with an ISS ≥ 16 and suffering from splenic or hepatic injuries were selected from our prospective trauma database. Absolute leukocyte numbers in peripheral blood were measured. White blood cell kinetics during the first 14 days were compared between splenectomized patients, patients treated surgically for liver trauma and nonoperatively treated individuals. RESULTS: A total of 129 patients with a mean ISS of 29 were included. Admission characteristics and leukocyte numbers were similar in all groups, except for slightly impaired hemodynamic status in patients with operatively treated liver injuries. On admission, leukocytosis occurred in all groups. During the first 24 h, leukopenia developed gradually, although significantly faster in the operatively treated patients. Thereafter, leukocyte levels normalized in all nonoperatively treated cases whereas leukocytosis persisted in operatively treated patients. This effect was significantly more prominent in splenectomized patients than all other conditions. CONCLUSIONS: This study demonstrates that surgery for intra-abdominal injuries is associated with an early drop in leucocyte numbers in peripheral blood. Moreover, splenectomy in severely injured patients is associated with an altered cellular immune response reflected by a persistent state of prominent leukocytosis after trauma.
Assuntos
Traumatismos Abdominais/cirurgia , Imunidade Celular , Leucócitos/imunologia , Baço/lesões , Esplenectomia/métodos , Ferimentos não Penetrantes/cirurgia , Traumatismos Abdominais/imunologia , Traumatismos Abdominais/metabolismo , Adulto , Feminino , Humanos , Contagem de Leucócitos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Baço/cirurgia , Ferimentos não Penetrantes/imunologia , Ferimentos não Penetrantes/metabolismo , Adulto JovemRESUMO
Although most acute skin wounds heal rapidly, non-healing skin ulcers represent an increasing and substantial unmet medical need that urgently requires effective therapeutics. Keratinocytes resurface wounds to re-establish the epidermal barrier by transitioning to an activated, migratory state, but this ability is lost in dysfunctional chronic wounds. Small-molecule regulators of keratinocyte plasticity with the potential to reverse keratinocyte malfunction in situ could offer a novel therapeutic approach in skin wound healing. Utilizing high-throughput phenotypic screening of primary keratinocytes, we identify such small molecules, including bromodomain and extra-terminal domain (BET) protein family inhibitors (BETi). BETi induce a sustained activated, migratory state in keratinocytes in vitro, increase activation markers in human epidermis ex vivo and enhance skin wound healing in vivo. Our findings suggest potential clinical utility of BETi in promoting keratinocyte re-epithelialization of skin wounds. Importantly, this novel property of BETi is exclusively observed after transient low-dose exposure, revealing new potential for this compound class.
Assuntos
Proteínas de Ciclo Celular/genética , Epiderme/efeitos dos fármacos , Reepitelização/efeitos dos fármacos , Úlcera Cutânea/tratamento farmacológico , Bibliotecas de Moléculas Pequenas/farmacologia , Fatores de Transcrição/genética , Ferimentos não Penetrantes/tratamento farmacológico , Animais , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo , Modelos Animais de Doenças , Epiderme/metabolismo , Epiderme/patologia , Transferência Ressonante de Energia de Fluorescência , Regulação da Expressão Gênica , Ensaios de Triagem em Larga Escala , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Cultura Primária de Células , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Precursores de Proteínas/antagonistas & inibidores , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Reepitelização/genética , Úlcera Cutânea/genética , Úlcera Cutânea/metabolismo , Úlcera Cutânea/patologia , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-Atividade , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Transcrição Gênica , Ferimentos não Penetrantes/genética , Ferimentos não Penetrantes/metabolismo , Ferimentos não Penetrantes/patologiaRESUMO
BACKGROUND: Previously, it has been shown that obesity is a risk factor for recovery, regeneration, and tissue repair after blunt trauma and can affect the rate of muscle recovery and collagen deposition after trauma. To date, lung tissue regeneration and extracellular matrix regulation in obese mice after injury has not been investigated in detail yet. METHODS: This study uses an established blunt thorax trauma model to analyze morphological changes and alterations on gene and protein level in lean or obese (diet-induced obesity for 16 ± 1 week) male C57BL/6 J mice at various time-points after trauma induction (1 h, 6 h, 24 h, 72 h and 192 h). RESULTS: Morphological analysis after injury showed lung parenchyma damage at early time-points in both lean and obese mice. At later time-points a better regenerative capacity of lean mice was observed, since obese animals still exhibited alveoli collapse, wall thickness as well as remaining filled alveoli structures. Although lean mice showed significantly increased collagen and fibronectin gene levels, analysis of collagen deposition showed no difference based on colorimetric quantification of collagen and visual assessment of Sirius red staining. When investigating the organization of the ECM on gene level, a decreased response of obese mice after trauma regarding extracellular matrix composition and organization was detectable. Differences in the lung tissue between the diets regarding early responding MMPs (MMP8/9) and late responding MMPs (MMP2) could be observed on gene and protein level. Obese mice show differences in regulation of extracellular matrix components compared to normal weight mice, which results in a decreased total MMP activity in obese animals during the whole regeneration phase. Starting at 6 h post traumatic injury, lean mice show a 50% increase in total MMP activity compared to control animals, while MMP activity in obese mice drops to 50%. CONCLUSIONS: In conclusion, abnormal regulation of the levels of extracellular matrix genes in the lung may contribute to an aberrant regeneration after trauma induction with a delay of repair and pathological changes of the lung tissue in obese mice.
Assuntos
Remodelação das Vias Aéreas/fisiologia , Matriz Extracelular/patologia , Pulmão/patologia , Obesidade/patologia , Traumatismos Torácicos/patologia , Ferimentos não Penetrantes/patologia , Animais , Dieta Hiperlipídica/efeitos adversos , Dieta Hiperlipídica/tendências , Matriz Extracelular/metabolismo , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/complicações , Obesidade/metabolismo , Traumatismos Torácicos/complicações , Traumatismos Torácicos/metabolismo , Tórax , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/metabolismoRESUMO
We investigated the relationships between circulating procoagulants and trauma severity, including cellular destruction, and the effects of thrombin generation on procoagulants in a rat blunt trauma model. The rats were subjected to tumbling blunt trauma, where they were tumbled for 0, 250, 500, or 1000 revolutions. Creatine kinase, nucleosome, and microparticle plasma levels increased gradually with trauma severity. Strong interrelationships were observed among creatine kinase, nucleosome, and microparticle levels. Time to initiation of thrombin generation shortened with increasing trauma severity. In accordance with trauma severity, prothrombin activity decreased, but the thrombin generation ratio increased. Time to initiation of thrombin generation and the thrombin generation ratio correlated with creatine kinase levels. In an in vitro study, a homogenized muscle solution, which included massive nucleosomes and microparticles, showed accelerated thrombin generation of plasma from healthy subjects. Procoagulants, such as microparticles and nucleosomes, are released from destroyed parenchymal cells immediately after external traumatic force, activating the coagulation cascade. The procoagulants shorten the time to initiation of thrombin generation. Furthermore, although coagulation factors are consumed, the thrombin generation ratio increases.
Assuntos
Micropartículas Derivadas de Células/metabolismo , Nucleossomos/metabolismo , Tecido Parenquimatoso/metabolismo , Ferimentos não Penetrantes/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos WistarRESUMO
Blunt chest trauma with hemorrhagic shock frequently induces pulmonary inflammation that leads to acute lung injury (ALI). The present study aimed to explore the protective effects of dexmedetomidine (Dex) in blunt chest trauma and hemorrhagic shockresuscitation (THSR)induced ALI by mediating nucleotide binding and oligomerization domainlike receptor family pyrin domaincontaining protein 3 (NLRP3) inflammasome formation in rats. An ALI model in rats induced by THSR was constructed and Dex was administered intraperitoneally (5 µg/kg/h) immediately after blunt chest trauma. Blood samples were collected for the determination of proinflammatory factor levels, and lung tissue specimens were harvested for wet/dry (W/D) weight ratio, hematoxylin and eosin staining, and transmission electron microscopy analyses. Additionally, malondialdehyde (MDA), superoxide dismutase (SOD), lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity were evaluated, and the expression of protein in lung tissues was examined via western blot analysis. Compared with the sham group, pathological alterations in the ALI group and the W/D ratios were significantly increased. MDA, LDH and MPO activity, and the levels of interleukin (IL)1ß, IL18, IL6 and tumor necrosis factorα were significantly elevated. NLRP3, apoptosisassociated specklike protein containing a caspase recruitment domain and caspase1 expression was significantly increased. Conversely, Dex treatment significantly reversed these changes. The present study demonstrated that by reducing inflammatory responses, Dex exerted protective effects against THSRALI in rats, potentially via the inhibition of NLRP3 signaling pathways.
Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Dexmedetomidina/administração & dosagem , Ressuscitação/efeitos adversos , Choque Hemorrágico/terapia , Traumatismos Torácicos/tratamento farmacológico , Ferimentos não Penetrantes/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Animais , Citocinas/metabolismo , Dexmedetomidina/farmacologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Injeções Intraperitoneais , L-Lactato Desidrogenase/metabolismo , Masculino , Malondialdeído/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peroxidase/metabolismo , Ratos , Choque Hemorrágico/etiologia , Choque Hemorrágico/metabolismo , Transdução de Sinais , Superóxido Dismutase , Traumatismos Torácicos/complicações , Traumatismos Torácicos/metabolismo , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/metabolismoRESUMO
Muscle pain is the most prevalent type of pain in the world, but treatment remains ineffective. Thus, it is relevant to develop trustable animal models to understand the involved pain mechanisms. Therefore, this study characterised the nociception and inflammation in a traumatic muscle injury model in rats. A single blunt trauma impact on the right gastrocnemius muscle of male Wistar rats (250-350 g) was used as model for muscle pain. Animals were divided into four groups (sham/no treatment; sham/diclofenac 1%; injury/no treatment; injury/diclofenac 1%) and the topical treatment with a cream containing 1% monosodium diclofenac (applied at 2, 6, 12, 24, and 46 h after muscle injury; 200 mg/muscle) was used as an anti-inflammatory control. Nociception (mechanical and cold allodynia, or nociceptive score) and locomotor activity were evaluated at 26 and 48 h after injury. Also, inflammatory and oxidative parameters were evaluated in gastrocnemius muscle and the creatine kinase (CK) activity and lactate/glicose levels in rat's serum and plasma, respectively. Muscle injury caused mechanical and cold allodynia, and increased nociceptive scores, without inducing locomotor impairment. This model also increased the inflammatory cells infiltration (seen by myeloperoxidase and N-acetyl-ß-D-glucosaminidase activities and histological procedure), nitric oxide, interleukin (IL)-1ß, IL-6, and dichlorofluorescein fluorescence in muscle samples; and CK activity and lactate/glicose ratio. The treatment with 1% monosodium diclofenac reduced inflammatory cells infiltration, dichlorofluorescein fluorescence and lactate/glicose levels. Thus, we characterised the traumatic muscle injury as a reproducible model of muscle pain, which makes it possible to evaluate promising antinociceptive and anti-inflammatory therapies.
Assuntos
Inflamação , Dor Musculoesquelética , Nociceptividade , Dor Nociceptiva , Ferimentos não Penetrantes , Administração Tópica , Analgésicos/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Comportamento Animal , Citocinas/metabolismo , Diclofenaco/administração & dosagem , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/fisiopatologia , Mediadores da Inflamação/metabolismo , Locomoção , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/lesões , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Dor Musculoesquelética/tratamento farmacológico , Dor Musculoesquelética/metabolismo , Dor Musculoesquelética/fisiopatologia , Nociceptividade/efeitos dos fármacos , Dor Nociceptiva/tratamento farmacológico , Dor Nociceptiva/metabolismo , Dor Nociceptiva/fisiopatologia , Estresse Oxidativo , Ratos Wistar , Ferimentos não Penetrantes/tratamento farmacológico , Ferimentos não Penetrantes/metabolismo , Ferimentos não Penetrantes/fisiopatologiaRESUMO
Proteomics offers the opportunity to identify and quantify many proteins and to explore how they correlate and interact with each other in biological networks. This study aimed to characterize changes in the muscle proteome during the destruction, repair, and early-remodeling phases after impact trauma in male Wistar rats. Muscle tissue was collected from uninjured control rats and rats that were euthanized between 6 h and 14 days after impact injury. Muscle tissue was analyzed using unbiased, data-independent acquisition LC-MS/MS. We identified 770 reviewed proteins in the muscle tissue, 296 of which were differentially abundant between the control and injury groups (P ≤ 0.05). Around 50 proteins showed large differences (≥10-fold) or a distinct pattern of abundance after injury. These included proteins that have not been identified previously in injured muscle, such as ferritin light chain 1, fibrinogen γ-chain, fibrinogen ß-chain, osteolectin, murinoglobulin-1, T-kininogen 2, calcium-regulated heat-stable protein 1, macrophage-capping protein, retinoid-inducible serine carboxypeptidase, ADP-ribosylation factor 4, Thy-1 membrane glycoprotein, and ADP-ribosylation factor-like protein 1. Some proteins increased between 6 h and 14 days, whereas other proteins increased in a more delayed pattern at 7 days after injury. Bioinformatic analysis revealed that various biological processes, including regulation of blood coagulation, fibrinolysis, regulation of wound healing, tissue regeneration, acute inflammatory response, and negative regulation of the immune effector process, were enriched in injured muscle tissue. This study advances the understanding of early muscle healing after muscle injury and lays a foundation for future mechanistic studies on interventions to treat muscle injury.
Assuntos
Coagulação Sanguínea , Fibrinólise , Inflamação , Músculo Esquelético/metabolismo , Regeneração , Cicatrização , Ferimentos não Penetrantes/metabolismo , Animais , Cromatografia Líquida , Biologia Computacional , Músculo Grácil/lesões , Músculo Grácil/metabolismo , Músculos Isquiossurais/lesões , Músculos Isquiossurais/metabolismo , Cinética , Masculino , Músculo Esquelético/lesões , Músculo Esquelético/patologia , Necrose , Proteoma/metabolismo , Proteômica , Ratos , Espectrometria de Massas em Tandem , Ferimentos não Penetrantes/patologiaRESUMO
OBJECTIVE: Innate immune response and particularly terminal complement complex (TCC) deposition are thought to be involved in the pathogenesis of posttraumatic osteoarthritis. However, the possible role of TCC in regulated cell death as well as chondrocyte hypertrophy and senescence has not been unraveled so far and was first addressed using an ex vivo human cartilage trauma-model. DESIGN: Cartilage explants were subjected to blunt impact (0.59 J) and exposed to human serum (HS) and cartilage homogenate (HG) with or without different potential therapeutics: RIPK1-inhibitor Necrostatin-1 (Nec), caspase-inhibitor zVAD, antioxidant N-acetyl cysteine (NAC) and TCC-inhibitors aurintricarboxylic acid (ATA) and clusterin (CLU). Cell death and hypertrophy/senescence-associated markers were evaluated on mRNA and protein level. RESULTS: Addition of HS resulted in significantly enhanced TCC deposition on chondrocytes and decrease of cell viability after trauma. This effect was potentiated by HG and was associated with expression of RIPK3, MLKL and CASP8. Cytotoxicity of HS could be prevented by heat-inactivation or specific inhibitors, whereby combination of Nec and zVAD as well as ATA exhibited highest cell protection. Moreover, HS+HG exposition enhanced the gene expression of CXCL1, IL-8, RUNX2 and VEGFA as well as secretion of IL-6 after cartilage trauma. CONCLUSIONS: Our findings imply crucial involvement of the complement system and primarily TCC in regulated cell death and phenotypic changes of chondrocytes after cartilage trauma. Inhibition of TCC formation or downstream signaling largely modified serum-induced pathophysiologic effects and might therefore represent a therapeutic target to maintain the survival and chondrogenic character of cartilage cells.
Assuntos
Morte Celular/genética , Condrócitos/metabolismo , Complexo de Ataque à Membrana do Sistema Complemento/genética , Hipertrofia/genética , Osteoartrite/genética , Ferimentos não Penetrantes/genética , Acetilcisteína/farmacologia , Idoso , Idoso de 80 Anos ou mais , Ácido Aurintricarboxílico/farmacologia , Cartilagem Articular/citologia , Morte Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Senescência Celular/genética , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Clusterina/farmacologia , Complexo de Ataque à Membrana do Sistema Complemento/antagonistas & inibidores , Complexo de Ataque à Membrana do Sistema Complemento/efeitos dos fármacos , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Inibidores Enzimáticos/farmacologia , Feminino , Sequestradores de Radicais Livres/farmacologia , Humanos , Imidazóis/farmacologia , Imunidade Inata/genética , Indóis/farmacologia , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/farmacologia , Osteoartrite/etiologia , Osteoartrite/metabolismo , Osteoartrite/patologia , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/metabolismoRESUMO
OBJECTIVES: Blunt chest (thoracic) trauma (TxT) is known to contribute to the development of secondary pulmonary complications. Of these, acute lung injury (ALI) is common especially in multiply injured patients and might not only be due to the direct trauma itself, but seems to be caused by ongoing and multifactorial inflammatory changes. Nevertheless, the exact mechanisms and contributing factors of the development of ALI following blunt chest trauma are still elusive. METHODS: 60 CL57BL/6N mice sustained either blunt chest trauma combined with laparotomy without further interventions or a double hit (DH) including TxT and cecal ligation puncture (CLP) after 24 h to induce ALI. Animals were killed either 6 or 24 h after the second procedure. Pulmonary expression of inflammatory mediators cxcl1, cxcl5, IL-1ß and IL-6, neutrophil infiltration and lung tissue damage using the Lung Injury Score (LIS) were determined. RESULTS: Next to a moderate increase in other inflammatory mediators, a significant increase in CXCL1, neutrophil infiltration and lung injury was observed early after TxT, which returned to baseline levels after 24 h. DH induced significantly increased gene expression of cxcl1, cxcl5, IL-1ß and IL-6 after 6 h, which was followed by the postponed significant increase in the protein expression after 24 h compared to controls. Neutrophil infiltration was significantly enhanced 24 h after DH compared to all other groups, and exerted a slight decline after 24 h. LIS has shown a significant increase after both 6 and 24 h compared to both control groups as well the late TxT group. CONCLUSION: Early observed lung injury with moderate inflammatory changes after blunt chest trauma recovered quickly, and therefore, may be caused by mechanical lung injury. In contrast, lung injury in the ALI group did not undergo recovery and is closely associated with significant changes of inflammatory mediators. This model may be used for further examinations of contributing factors and therapeutic strategies to prevent ALI.
Assuntos
Lesão Pulmonar Aguda/metabolismo , Inflamação/metabolismo , Sepse/metabolismo , Traumatismos Torácicos/metabolismo , Ferimentos não Penetrantes/metabolismo , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Animais , Ceco/cirurgia , Quimiocina CXCL1/imunologia , Quimiocina CXCL1/metabolismo , Quimiocina CXCL5/imunologia , Quimiocina CXCL5/metabolismo , Contusões/imunologia , Contusões/metabolismo , Contusões/patologia , Modelos Animais de Doenças , Inflamação/imunologia , Inflamação/patologia , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Interleucina-6/imunologia , Interleucina-6/metabolismo , Laparotomia , Ligadura , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Camundongos , Traumatismo Múltiplo/imunologia , Traumatismo Múltiplo/metabolismo , Neutrófilos/imunologia , Neutrófilos/patologia , Punções , Distribuição Aleatória , Sepse/imunologia , Sepse/patologia , Traumatismos Torácicos/imunologia , Traumatismos Torácicos/patologia , Ferimentos não Penetrantes/imunologia , Ferimentos não Penetrantes/patologiaRESUMO
INTRODUCTION: Bosentan is an endothelin-1 receptor antagonist with anti-inflammatory, antioxidant, and antiproliferative effects. We aimed to evaluate its effects on lung tissue in a pulmonary contusion (PC) model. MATERIALS AND METHODS: The rats were randomly divided into five groups: PC3: PC evaluated on the 3rd day (n = 8), PC-B3: PC enteral bosentan 100 mg/kg/day, for 3 days (n = 8), PC7: PC evaluated on the 7th day (n = 7), PC-B7: PC 7 days bosentan 100 mg/kg/day, for 7 days (n = 8), C: control (n = 6). Unilateral lung contusion was created by dropping a metal weight onto the chest. The rats were sacrificed on the 3rd or the 7th days. The lung tissue was evaluated histopathologically for alveolar edema, congestion, and leukocyte infiltration, biochemically for malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels, and immunohistochemically for inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and apoptosis scores. RESULTS: Alveolar edema, congestion, and leukocyte infiltration scores were increased in all groups compared with the control group (p < 0.05) and decreased in bosentan-treated groups compared with the relevant nontreated groups (p < 0.05). Fibrosis was observed only in PC7 and PC-B7 groups. Bosentan did not have any effect on fibrosis development. iNOS and eNOS levels were higher in all groups compared with the control (p < 0.05) without a difference in the nontreated versus treated groups (p > 0.05). Bosentan treatment caused decreased MDA and increased SOD levels in comparison to the nontreated groups (p < 0.05). Tissue NO levels did not show any significant difference among groups. PC groups had higher levels of apoptosis compared with the control group (p < 0.05). The degree of apoptosis decreased in bosentan-treated groups compared with the nontreated groups (p < 0.05). CONCLUSION: PC causes progressive lung tissue damage. Bosentan reduced leukocyte infiltration and alveolar edema and congestion caused by PC. It also decreased MDA levels and increased SOD levels. Bosentan prevents tissue damage by inhibiting acute inflammatory response and reduces oxidative stress secondary to inflammation. It has therapeutic effects on apoptosis.
Assuntos
Bosentana/uso terapêutico , Contusões/tratamento farmacológico , Antagonistas dos Receptores de Endotelina/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Ferimentos não Penetrantes/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Contusões/metabolismo , Contusões/patologia , Endotelina-1/antagonistas & inibidores , Marcação In Situ das Extremidades Cortadas , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Ferimentos não Penetrantes/metabolismo , Ferimentos não Penetrantes/patologiaRESUMO
Hemorrhagic shock (HS) accounts for 30% to 40% of trauma-induced mortality, which is due to multi-organ-failure subsequent to systemic hyper-inflammation, triggered by hypoxemia and tissue ischemia. The slow-releasing, mitochondria-targeted H2S donor AP39 exerted beneficial effects in several models of ischemia-reperfusion injury and acute inflammation. Therefore, we tested the effects of AP39-treatment in a murine model of combined blunt chest trauma (TxT) and HS with subsequent resuscitation. METHODS: After blast wave-induced TxT or sham procedure, anesthetized and instrumented mice underwent 1 h of hemorrhage followed by 4âh of resuscitation comprising an i.v. bolus injection of 100 or 10 nmolâkg AP39 or vehicle, retransfusion of shed blood, fluid resuscitation, and norepinephrine. Lung mechanics and gas exchange were assessed together with hemodynamics, metabolism, and acid-base status. Blood and tissue samples were analyzed for cytokine and chemokine levels, western blot, immunohistochemistry, mitochondrial oxygen consumption (JO2), and histological changes. RESULTS: High dose AP39 attenuated systemic inflammation and reduced the expression of inducible nitric oxide synthase (iNOS) and IκBα expression in lung tissue. In the combined trauma group (TxTâ+âHS), animals treated with high dose AP39 presented with the lowest mean arterial pressure and thus highest norepinephrine requirements and higher mortality. Low dose AP39 had no effects on hemodynamics, leading to unchanged norepinephrine requirements and mortality rates. CONCLUSION: AP39 is a systemic anti-inflammatory agent. In our model of trauma with HS, there may be a narrow dosing and timing window due to its potent vasodilatory properties, which might result in or contribute to aggravation of circulatory shock-related hypotension.
Assuntos
Mitocôndrias/metabolismo , Compostos Organofosforados/uso terapêutico , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/metabolismo , Tionas/uso terapêutico , Traumatismos Torácicos/tratamento farmacológico , Traumatismos Torácicos/metabolismo , Ferimentos e Lesões/tratamento farmacológico , Ferimentos e Lesões/metabolismo , Animais , Temperatura Corporal , Quimiocinas/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Immunoblotting , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ferimentos não Penetrantes/tratamento farmacológico , Ferimentos não Penetrantes/metabolismoRESUMO
Pseudin-2, isolated from the frog Pseudis paradoxa, exhibits potent antibacterial activity but also cytotoxicity. In an effort to develop clinically applicable antimicrobial peptides (AMPs), we designed pseudin-2 analogs with Lys substitutions, resulting in elevated amphipathic α-helical structure and cationicity. In addition, truncated analogs of pseudin-2 and Lys-substituted peptides were synthesized to produce linear 18-residue amphipathic α-helices, which were further investigated for their mechanism and functions. These truncated analogs exhibited higher antimicrobial activity and lower cytotoxicity than pseudin-2. In particular, Pse-T2 showed marked pore formation, permeabilization of the outer/inner bacterial membranes, and DNA binding. Fluorescence spectroscopy and scanning electron microscopy showed that Pse-T2 kills bacterial cells by disrupting membrane integrity. In vivo, wounds infected with multidrug-resistant (MDR) Pseudomonas aeruginosa healed significantly faster when treated with Pse-T2 than did untreated wounds or wounds treated with ciprofloxacin. Moreover, Pse-T2 facilitated infected-wound closure by reducing inflammation through suppression of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α). These data suggest that the small antimicrobial peptide Pse-T2 could be useful for future development of therapeutic agents effective against MDR bacterial strains.
Assuntos
Proteínas de Anfíbios/farmacologia , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Ferimentos não Penetrantes/tratamento farmacológico , Proteínas de Anfíbios/síntese química , Animais , Antibacterianos/síntese química , Peptídeos Catiônicos Antimicrobianos/síntese química , Anuros , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Ciprofloxacina , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/biossíntese , Interleucina-6/antagonistas & inibidores , Interleucina-6/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Peptídeos/síntese química , Engenharia de Proteínas , Infecções por Pseudomonas/metabolismo , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pele/efeitos dos fármacos , Pele/lesões , Pele/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese , Cicatrização/efeitos dos fármacos , Ferimentos não Penetrantes/metabolismo , Ferimentos não Penetrantes/patologiaRESUMO
RATIONALE: The pathophysiology of persistent injury-associated anemia is incompletely understood, and human data are sparse. OBJECTIVES: To characterize persistent injury-associated anemia among critically ill trauma patients with the hypothesis that severe trauma would be associated with neuroendocrine activation, erythropoietin dysfunction, iron dysregulation, and decreased erythropoiesis. METHODS: A translational prospective observational cohort study comparing severely injured, blunt trauma patients who had operative fixation of a hip or femur fracture (n = 17) with elective hip repair patients (n = 22). Bone marrow and plasma obtained at the index operation were assessed for circulating catecholamines, systemic inflammation, erythropoietin, iron trafficking pathways, and erythroid progenitor growth. Bone marrow was also obtained from healthy donors from a commercial source (n = 8). MEASUREMENTS AND MAIN RESULTS: During admission, trauma patients had a median of 625 ml operative blood loss and 5 units of red blood cell transfusions, and Hb decreased from 10.5 to 9.3 g/dl. Compared with hip repair, trauma patients had higher median plasma norepinephrine (21.9 vs. 8.9 ng/ml) and hepcidin (56.3 vs. 12.2 ng/ml) concentrations (both P < 0.05). Bone marrow erythropoietin and erythropoietin receptor expression were significantly increased among patients undergoing hip repair (23% and 14% increases, respectively; both P < 0.05), but not in trauma patients (3% and 5% increases, respectively), compared with healthy control subjects. Trauma patients had lower bone marrow transferrin receptor expression than did hip repair patients (57% decrease; P < 0.05). Erythroid progenitor growth was decreased in trauma patients (39.0 colonies per plate; P < 0.05) compared with those with hip repair (57.0 colonies per plate; P < 0.05 compared with healthy control subjects) and healthy control subjects (66.5 colonies per plate). CONCLUSIONS: Severe blunt trauma was associated with neuroendocrine activation, erythropoietin dysfunction, iron dysregulation, erythroid progenitor growth suppression, and persistent injury-associated anemia. Clinical trial registered with www.clinicaltrials.gov (NCT 02577731).
Assuntos
Anemia/complicações , Medula Óssea/metabolismo , Inflamação/complicações , Ferimentos não Penetrantes/complicações , Adulto , Idoso , Anemia/metabolismo , Anemia/fisiopatologia , Medula Óssea/fisiopatologia , Estudos de Coortes , Estado Terminal , Feminino , Fêmur/lesões , Fêmur/cirurgia , Fraturas do Quadril/fisiopatologia , Fraturas do Quadril/cirurgia , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ferimentos não Penetrantes/metabolismo , Ferimentos não Penetrantes/cirurgia , Adulto JovemRESUMO
Chronic non-healing wounds represent one of the most common complications of diabetes and need advanced treatment strategies. Exosomes are key mediators of cell paracrine action and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of exosomes from human urine-derived stem cells (USC-Exos) on diabetic wound healing and the underlying mechanism. Methods: USCs were characterized by flow cytometry and multipotent differentiation potential analyses. USC-Exos were isolated from the conditioned media of USCs and identified by transmission electron microscopy and flow cytometry. A series of functional assays in vitro were performed to assess the effects of USC-Exos on the activities of wound healing-related cells. Protein profiles in USC-Exos and USCs were examined to screen the candidate molecules that mediate USC-Exos function. The effects of USC-Exos on wound healing in streptozotocin-induced diabetic mice were tested by measuring wound closure rates, histological and immunofluorescence analyses. Meanwhile, the role of the candidate protein in USC-Exos-induced regulation of angiogenic activities of endothelial cells and diabetic wound healing was assessed. Results: USCs were positive for CD29, CD44, CD73 and CD90, but negative for CD34 and CD45. USCs were able to differentiate into osteoblasts, adipocytes and chondrocytes. USC-Exos exhibited a cup- or sphere-shaped morphology with a mean diameter of 51.57 ± 2.93 nm and positive for CD63 and TSG101. USC-Exos could augment the functional properties of wound healing-related cells including the angiogenic activities of endothelial cells. USC-Exos were enriched in the proteins that are involved in regulation of wound healing-related biological processes. Particularly, a pro-angiogenic protein called deleted in malignant brain tumors 1 (DMBT1) was highly expressed in USC-Exos. Further functional assays showed that DMBT1 protein was required for USC-Exos-induced promotion of angiogenic responses of cultured endothelial cells, as well as angiogenesis and wound healing in diabetic mice. Conclusion: Our findings suggest that USC-Exos may represent a promising strategy for diabetic soft tissue wound healing by promoting angiogenesis via transferring DMBT1 protein.
Assuntos
Meios de Cultivo Condicionados/farmacologia , Diabetes Mellitus Experimental/terapia , Exossomos/química , Neovascularização Fisiológica/efeitos dos fármacos , Receptores de Superfície Celular/genética , Cicatrização/efeitos dos fármacos , Ferimentos não Penetrantes/terapia , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Proteínas de Ligação ao Cálcio , Diferenciação Celular , Movimento Celular , Proliferação de Células , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Meios de Cultivo Condicionados/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Receptores de Superfície Celular/metabolismo , Pele/efeitos dos fármacos , Pele/lesões , Pele/metabolismo , Células-Tronco/química , Células-Tronco/citologia , Células-Tronco/metabolismo , Estreptozocina , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor , Urina/química , Ferimentos não Penetrantes/metabolismo , Ferimentos não Penetrantes/patologiaRESUMO
Blunt chest trauma with hemorrhagic shock (THS) frequently induces pulmonary inflammation that leads to acute lung injury (ALI). Penehyclidine hydrochloride (PHC) possesses antiinflammatory properties that may attenuate the systemic inflammatory response. The present study aimed to evaluate the molecular mechanism of PHC in modifying THSinduced ALI in rats. Rats underwent either THS or a sham procedure. At 6 h subsequent to blunt chest trauma, arterial blood was drawn for blood gas and proinflammatory factors analyses, and lung tissue samples were collected to examine pulmonary histopathological alterations, the wet/dry weight ratio, myeloperoxidase activity, and the protein expression levels of Toll-like receptor 4 (TLR4), phosphorylated (p)p38 mitogenactivated protein kinase (MAPK), nuclear factor (NF)κB and activator protein1 (AP1). THS caused significant reductions in heart rate and mean arterial blood pressure, and was associated with significant increases in tumor necrosis factorα, interleukin (IL)6, IL1ß, pp38MAPK, NFκB and AP1 activation, in addition to TLR4 expression, in the lung. PHC effectively attenuated THSinduced ALI, and inhibited TLR4 expression, reduced the activation of pp38MAPK, NFκB and AP1, and downregulated the expression of proinflammatory mediators. In conclusion, the results of the present study demonstrated that PHC may exert an antiinflammatory effect and attenuate THSinduced ALI by inhibiting the TLR4 signaling pathway. These preclinical findings may offer a novel therapeutic strategy to restrict TLR4 overactivation in ALI.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Quinuclidinas/farmacologia , Choque Hemorrágico/tratamento farmacológico , Receptor 4 Toll-Like/metabolismo , Ferimentos não Penetrantes/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Choque Hemorrágico/metabolismo , Choque Hemorrágico/patologia , Tórax , Ferimentos não Penetrantes/metabolismo , Ferimentos não Penetrantes/patologiaRESUMO
Maggot extract (ME) accelerates rat skin wound healing, however its effect on cell maintenance in wound tissues remains unclear. Bcell lymphoma (Bcl) 2associated athanogene (BAG)3 inhibits apoptosis and promotes autophagy by associating with Bcl2 or Beclin 1. Bcl2, the downstream effector of signal transducer and activator of transcription 3 signaling, is enhanced in MEtreated wound tissues, which may reinforce the Bcl2 antiapoptotic activity and/or cooperate with Beclin 1 to regulate autophagy during wound healing. The present study investigated expression levels of BAG3, Bcl2, Beclin 1 and light chain (LC)3 levels in rat skin wound tissues in the presence and absence of ME treatment. The results revealed frequent TUNELnegative cell death in the wound tissues in the early three days following injury, irrespective to ME treatment. TUNELpositive cells appeared in the wound tissues following 4 days of injury and 150 µg/ml ME efficiently reduced apoptotic rate and enhanced BAG3 and Bcl2 expression. Elevated Beclin 1 and LC3 levels and an increased LC3 II ratio were revealed in the MEtreated tissues during the wound healing. The results of the present study demonstrate the antiapoptotic effects of BAG3 and Bcl2 in MEpromoted wound healing. Beclin 1/LC3 mediated autophagy may be favorable in maintaining cell survival in the damaged tissues and MEupregulated BAG3 may enhance its activity.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/agonistas , Proteínas Reguladoras de Apoptose/agonistas , Misturas Complexas/farmacologia , Larva/química , Cicatrização/efeitos dos fármacos , Ferimentos não Penetrantes/terapia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/efeitos dos fármacos , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Proliferação de Células/efeitos dos fármacos , Misturas Complexas/isolamento & purificação , Dípteros/química , Regulação da Expressão Gênica , Masculino , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Cicatrização/genética , Ferimentos não Penetrantes/genética , Ferimentos não Penetrantes/metabolismo , Ferimentos não Penetrantes/patologiaRESUMO
BACKGROUND: The clinical relevance of blunt (thoracic) chest trauma (TxT) and hemorrhagic shock is indisputable due to the high prevalence of this injury type, as well as its close association with mortality and/or preventable deaths. Furthermore, there is an ongoing discussion about the influence of alcohol in trauma patients. Thus, we established a model of TxT followed by hemorrhagic shock with resuscitation (H/R) in alcohol-intoxicated rats. METHODS: Depending on group allocation, 12 (subacute) or 2 (acute) hours before experimentation, the animals received a single oral dose of alcohol (ethanol [EtOH]) or saline (NaCl) followed by TxT, hemorrhagic shock (35 ± 3 mm Hg), and resuscitation (TxT + H/R). Arterial blood gas analyses and continuous monitoring of blood pressure were performed during the experimentation period. Survival during the experimentation procedure was determined. RESULTS: Subacute and acute EtOH group exhibited lower baseline mean arterial blood pressure values compared with the corresponding NaCl group, respectively. Both EtOH groups showed lower maximal bleed-out volume, which was necessary to induce hemorrhagic shock compared to NaCl groups, and the recovery during the resuscitation period was attenuated. During the experimentation in all groups, a trend to acidic pH was observed. Acute EtOH group showed lowest pH values compared to all other groups. Higher pCO2 values were observed in both EtOH groups. All groups developed negative base excess and decreasing HCO3- values until the end of hemorrhagic shock and showed increasing base excess and HCO3- values during resuscitation. Significantly higher mortality rate was found in the acute EtOH group. CONCLUSIONS: This study indicates that alcohol limits the metabolic and respiratory compensation capability, thereby promoting mortality.
Assuntos
Consumo Excessivo de Bebidas Alcoólicas/fisiopatologia , Mecânica Respiratória/efeitos dos fármacos , Choque Hemorrágico/fisiopatologia , Traumatismos Torácicos/fisiopatologia , Ferimentos não Penetrantes/fisiopatologia , Acidose/sangue , Acidose/induzido quimicamente , Doença Aguda , Animais , Pressão Arterial/efeitos dos fármacos , Consumo Excessivo de Bebidas Alcoólicas/complicações , Consumo Excessivo de Bebidas Alcoólicas/metabolismo , Gasometria , Depressores do Sistema Nervoso Central/sangue , Modelos Animais de Doenças , Etanol/sangue , Feminino , Concentração de Íons de Hidrogênio , Ratos , Ratos Endogâmicos Lew , Ressuscitação , Choque Hemorrágico/complicações , Choque Hemorrágico/metabolismo , Traumatismos Torácicos/complicações , Traumatismos Torácicos/metabolismo , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/metabolismoRESUMO
MicroRNAs (miRs) are small non-coding RNAs that post-transcriptionally control gene expression. Inhibition of miRs by antisense RNAs (antimiRs) might be a therapeutic option for many diseases, but systemic inhibition can have adverse effects. Here we show that light-activatable antimiRs efficiently and locally restricted target miR activity in vivo. We use an antimiR-92a and establish a therapeutic benefit in diabetic wound healing. AntimiR-92a is modified with photolabile protecting groups, so called 'cages'. Irradiation activates intradermally injected caged antimiR-92a without substantially affecting miR-92a expression in other organs. Light activation of caged antimiR-92a improves healing in diabetic mice to a similar extent as conventional antimiRs and derepresses the miR-92a targets Itga5 and Sirt1, thereby regulating wound cell proliferation and angiogenesis. These data show that light can be used to locally activate therapeutically active antimiRs in vivo.
Assuntos
Antagomirs/genética , MicroRNAs/antagonistas & inibidores , Neovascularização Fisiológica/efeitos da radiação , Pele/efeitos da radiação , Cicatrização/efeitos da radiação , Ferimentos não Penetrantes/terapia , Animais , Antagomirs/administração & dosagem , Antagomirs/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Regulação da Expressão Gênica , Humanos , Injeções Intradérmicas , Integrina alfa5/genética , Integrina alfa5/metabolismo , Rim/metabolismo , Luz , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Fisiológica/genética , Especificidade de Órgãos , Processos Fotoquímicos , Transdução de Sinais , Sirtuína 1/genética , Sirtuína 1/metabolismo , Pele/irrigação sanguínea , Pele/lesões , Pele/metabolismo , Cicatrização/genética , Ferimentos não Penetrantes/genética , Ferimentos não Penetrantes/metabolismo , Ferimentos não Penetrantes/patologiaRESUMO
Foetal microchimeric cells (FMCs) traffic into maternal circulation during pregnancy and persist for decades after delivery. Upon maternal injury, FMCs migrate to affected sites where they participate in tissue healing. However, the specific signals regulating the trafficking of FMCs to injury sites had to be identified. Here we report that, in mice, a subset of FMCs implicated in tissue repair displays CD11b+ CD34+ CD31+ phenotype and highly express C-C chemokine receptor 2 (Ccr2). The Ccr2 ligand chemokine ligand 2 (Ccl2) enhances the recruitment of FMCs to maternal wounds where these cells transdifferentiate into endothelial cells and stimulate angiogenesis through Cxcl1 secretion. Ccl2 administration improves delayed maternal wound healing in pregnant and postpartum mice but never in virgin ones. This role of Ccl2/Ccr2 signalling opens new strategies for tissue repair through natural stem cell therapy, a concept that can be later applied to other types of maternal diseases.
Assuntos
Quimiocina CCL2/genética , Células Progenitoras Endoteliais/metabolismo , Neovascularização Fisiológica , Receptores CCR2/genética , Cicatrização/efeitos dos fármacos , Ferimentos não Penetrantes/genética , Animais , Antígenos CD34/genética , Antígenos CD34/metabolismo , Antígeno CD11b/genética , Antígeno CD11b/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CCL2/farmacologia , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Células Progenitoras Endoteliais/citologia , Feminino , Feto , Regulação da Expressão Gênica , Camundongos , Circulação Placentária/fisiologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Gravidez , Receptores CCR2/metabolismo , Transdução de Sinais , Cicatrização/genética , Ferimentos não Penetrantes/tratamento farmacológico , Ferimentos não Penetrantes/metabolismo , Ferimentos não Penetrantes/patologiaRESUMO
OBJECTIVE: We retrospectively analyzed trauma patients who were transported by a physician-staffed helicopter (doctor helicopter) to investigate the clinical significance of the fibrinogen degradation product (FDP) level on arrival. METHODS: From February 2011 to July 2016, a medical chart review was retrospectively performed for all patients with trauma who were transported by the doctor helicopter. The subjects were divided into 2 groups: a survival group and a fatal group. RESULTS: There were 135 patients in the survival group and 16 in the fatal group. The ratio of head injury, value of Injury Severity Score (ISS), and level of FDP in the fatal group were significantly greater than in the survival group. The average Glasgow Coma Scale and systolic blood pressure in the fatal group were significantly smaller than in the survival group. The FDP level at arrival was positively associated with the ISS (R = 0.74, P < .0001). After excluding subjects with shock, unconsciousness, and head injury, the FDP level was still positively associated with the ISS (R = 0.60, P < .0001). CONCLUSION: Therefore, the FDP level may be a useful biochemical parameter for the initial evaluation of the severity of trauma, even in blunt trauma patients without head injury or with stable vital signs.