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1.
Int Orthop ; 45(9): 2355-2363, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34357432

RESUMO

PURPOSE: To assess which pre-operative parameters correlate with wound revisions after an extended lateral approach to the calcaneus. METHODS: Pre-operative laser-Doppler spectrophotometry was applied in patients undergoing open reduction and internal fixation. The number of wound revisions was recorded during pos-toperative follow-up. Spearman rho analysis was used to identify factors associated with wound revision and receiver operator characteristics curves were calculated for the identified factors. RESULTS: Thirty-four patients (29 men, 5 women; 37 calcanei) with a mean patient age of 43 ± 14 years were analyzed. The minimal oxygen saturation value at the five measurement locations as well as the minimal value for flow correlated negatively with wound revisions (p value = 0.025 and 0.038, respectively). The area under the curve for the pre-operative minimal value of oxygen saturation was 0.841 (95%CI 0.64-1.00, p = 0.028), indicating a good accuracy as a test to predict wound revision. CONCLUSION: A pre-operative oxygen saturation of at least 20.5% across five measurement points along the anticipated incision identified all patients not needing a wound revision (negative predictive value 100%). On the other hand, patients with at least one measurement below 20.5% were at risk for wound revision surgery (sensitivity 100%, specificity 48.5%). ClinicalTrials.gov NCT01264146.


Assuntos
Calcâneo , Fraturas Ósseas , Adulto , Calcâneo/diagnóstico por imagem , Calcâneo/cirurgia , Feminino , Fixação Interna de Fraturas/efeitos adversos , Fraturas Ósseas/cirurgia , Humanos , Lasers , Masculino , Pessoa de Meia-Idade , Oxigênio , Reoperação , Estudos Retrospectivos , Espectrofotometria
2.
Unfallchirurg ; 124(4): 333-337, 2021 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-33599791

RESUMO

Osteochondral lesions (OCL) of the talus can be caused by isolated or recurrent traumatic events. The established surgical treatment techniques are predominantly based on defect coverage by stimulation of fibrous cartilage or transplantation of osteochondral tissue or chondrocytes. An alternative is the preservation of an intact autochthonous hyaline cartilage surface with reconstruction of the subchondral lamella and the natural joint congruence. This anatomical technique can be used for selected acute and chronic OCL and can frequently be carried out arthroscopically. This article presents the indications, contraindications, advantages and targets as well as the planning and execution of arthroscopically assisted transmalleolar internal fixation of a lateral OCL of the talus.


Assuntos
Cartilagem Articular , Tálus , Artroscopia , Condrócitos , Humanos , Tálus/diagnóstico por imagem , Tálus/cirurgia
3.
Unfallchirurg ; 124(4): 319-332, 2021 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-33666680

RESUMO

Osteochondral lesions (OCL) of the talus are defined as chondral damage with subchondral involvement. The traumatic etiology is important; in particular, sprains and fractures can lead to lesions of the articular surface and the subchondral plate. As a result, unstable lesions and subchondral cysts can trigger substantial persistent pain and functional impairments. A primary conservative treatment can be considered and is especially recommended in children and adolescents; however, return to previous sports activity and level is often not achieved. The principles of reconstructive surgical management include internal fixation of osteochondral fragments, bone marrow stimulation, autologous membrane-augmented chondrogenesis ± bone grafting, osteochondral transfer, retrograde techniques ± bone grafting, (matrix-associated) autologous chondrocyte implantation and autologous osteoperiosteal graft from the iliac crest. Additional surgical procedures for ankle stabilization and deformity correction should be considered if necessary.


Assuntos
Cartilagem Articular , Fraturas Intra-Articulares , Tálus , Adolescente , Artroscopia , Transplante Ósseo , Criança , Humanos , Ílio , Tálus/diagnóstico por imagem , Tálus/cirurgia , Transplante Autólogo
4.
Int J Mol Sci ; 21(9)2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32370039

RESUMO

It was hypothesized that strontium (Sr)-doped ß-tricalcium phosphate (TCP)-based scaffolds have a positive effect on the regeneration of large bone defects (LBD). Readouts in our mice models were nuclear factor-kappa beta (NF-κB) activity and vascular endothelial growth factor receptor-2 (VEGFR-2) promoter activity during the healing process. A 2-mm critical-size femoral fracture was performed in transgenic NF-κB- and VEGFR-2-luciferase reporter mice. The fracture was filled with a 3D-printed ß-TCP scaffold with or without Sr. A bioluminescence in-vivo imaging system was used to sequentially investigate NF-κB and VEGFR-2 expression for two months. After sacrifice, soft and osseous tissue formation in the fracture sites was histologically examined. NF-κB activity increased in the ß-TCP + Sr group in the latter stage (day 40-60). VEGFR-2 activity increased in the + Sr group from days 0-15 but decreased and showed significantly less activity than the ß-TCP and non-scaffold groups from days 40-60. The new bone formation and soft tissue formation in the + Sr group were significantly higher than in the ß-TCP group, whereas the percentage of osseous tissue formation in the ß-TCP group was significantly higher than in the ß-TCP + Sr group. We analyzed longitudinal VEGFR-2 promoter activity and NF-κB activity profiles, as respective agents of angiogenesis and inflammation, during LBD healing. The extended inflammation phase and eventually more rapid resorption of scaffold caused by the addition of strontium accelerates temporary bridging of the fracture gaps. This finding has the potential to inform an improved treatment strategy for patients who suffer from osteoporosis.


Assuntos
Fosfatos de Cálcio/química , NF-kappa B/genética , Fosfatidiletanolaminas/química , Regiões Promotoras Genéticas , Estrôncio/química , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Animais , Regeneração Óssea , Substitutos Ósseos , Osso e Ossos/metabolismo , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , NF-kappa B/metabolismo , Alicerces Teciduais , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
5.
Unfallchirurg ; 123(2): 143-154, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-32016493

RESUMO

Posttraumatic kyphotic deformities of the thoracolumbar spine may result in significant clinical complaints. If conservative treatment is not successful, surgical correction of the kyphosis becomes an option. In contrast to degenerative deformities, posttraumatic kyphotic deformities are usual limited to few segments and can be treated with shorter constructs. The surgical strategy depends on the rigidity and the localization of the posttraumatic kyphotic deformity. In this respect purely posterior approaches and combined posteroanterior surgical approaches are available each with different advantages and disadvantages.


Assuntos
Cifose , Fusão Vertebral , Traumatismos da Coluna Vertebral , Tratamento Conservador , Humanos , Cifose/etiologia , Cifose/cirurgia , Vértebras Lombares , Osteotomia , Traumatismos da Coluna Vertebral/cirurgia , Vértebras Torácicas , Resultado do Tratamento
6.
Calcif Tissue Int ; 105(4): 341-352, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31236620

RESUMO

Fracture healing is a natural process that recapitulates embryonic skeletal development. In the early phase after fracture, reactive oxygen species (ROS) are produced under inflammatory and ischemic conditions due to vessel injury and soft tissue damage, leading to cell death. Usually, such damage during the course of fracture healing can be largely prevented by protective mechanisms and functions of antioxidant enzymes. However, intrinsic oxidative stress can cause excessive toxic radicals, resulting in irreversible damage to cells associated with bone repair during the fracture healing process. Clinically, patients with type-2 diabetes mellitus, osteoporosis, habitual drinkers, or heavy smokers are at risk of impaired fracture healing due to elevated oxidative stress. Although increased levels of oxidative stress markers upon fracture and effects of antioxidants on fracture healing have been reported, a detailed understanding of what causes impaired fracture healing under intrinsic conditions of oxidative stress is lacking. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been identified as a key transcriptional regulator of the expression of antioxidants and detoxifying enzymes. It further not only plays a crucial role in preventing degenerative diseases in multiple organs, but also during fracture healing. This narrative review evaluates the influence of intrinsic oxidative stress on fracture healing and sheds new light on the intriguing role of Nrf2 during bone regeneration in pathological fractures.


Assuntos
Consolidação da Fratura/fisiologia , Regulação da Expressão Gênica/fisiologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/fisiologia , Animais , Humanos , Fator 2 Relacionado a NF-E2/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia
7.
Unfallchirurg ; 122(11): 885-900, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31650191

RESUMO

The incidence of periprosthetic hip fractures is increasing due to the increase in endoprosthetic hip replacements. These fractures require a staged and individual treatment concept with the aim of mobilization of the patient as early as possible. The special challenge in the diagnostics is to identify pre-existing signs of loosening of the prosthesis. When the prosthesis is still firmly fixed femoral fractures can be treated with angular stable osteosynthesis. Loosened stems usually have to be revised, mostly in combination with osteosynthesis. Fractures around the acetabulum with a fixed cup can be treated nonoperatively or with osteosynthesis, while loosened cups have to be revised. In revision surgery the stabilization of the dorsal column is crucial for a successful outcome.


Assuntos
Artroplastia de Quadril/efeitos adversos , Fraturas do Fêmur , Fraturas do Quadril , Fraturas Periprotéticas/etiologia , Acetábulo/lesões , Artroplastia de Quadril/métodos , Fraturas do Fêmur/diagnóstico , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/terapia , Fraturas do Quadril/diagnóstico , Fraturas do Quadril/etiologia , Fraturas do Quadril/terapia , Humanos , Fraturas Periprotéticas/diagnóstico , Fraturas Periprotéticas/terapia , Falha de Prótese , Reoperação
8.
Unfallchirurg ; 122(5): 387-403, 2019 May.
Artigo em Alemão | MEDLINE | ID: mdl-31025047

RESUMO

In the treatment of pelvic ring and acetabular fractures percutaneous screw osteosynthesis provides the advantage of minimal soft tissue damage. The techniques are frequently used in combination with open osteosynthesis and less frequently as stand-alone procedures. A preoperative planning with the aid of computed tomography (CT) and knowledge of the intraoperative radiological fluoroscopy adjustment are prerequisites for an accurate placement of the screws. This article describes the indications and techniques for frequently used percutaneous screws.


Assuntos
Parafusos Ósseos , Acetábulo , Fluoroscopia , Fixação Interna de Fraturas , Fraturas Ósseas , Humanos , Pelve
9.
J Musculoskelet Neuronal Interact ; 18(1): 62-70, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29504580

RESUMO

PURPOSE: This review addressed the question of whether minimally invasive surgery after traumatic thoracolumbar spine fractures can reduce paraspinal muscle injury, limit changes in muscular structure and function, and lead to better functional outcome. Special emphasis was given to studies using imaging techniques or electromyography to evaluate the lumbar multifidus muscle structure and function. METHODS: The authors searched the literature in the PubMed/Medline, EMBASE, by cross-referencing and additional hand search. Included were comparative studies between conventional open and minimally invasive or percutaneous surgical approaches. Twelve studies were included. RESULTS AND CONCLUSIONS: The literature review supports the assumption that minimally invasive surgery preserves muscles for the early post-operative period, even though the level of evidence is still low. The correlation of changes in muscular structure to pain, strength, disability, and quality of life remains ambiguous and should be addressed in further studies with a focus on the surgical approach.


Assuntos
Vértebras Lombares/cirurgia , Músculos Paraespinais/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgia , Humanos , Vértebras Lombares/lesões , Procedimentos Cirúrgicos Minimamente Invasivos , Procedimentos Ortopédicos , Músculos Paraespinais/fisiopatologia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/fisiopatologia , Vértebras Torácicas/lesões , Resultado do Tratamento
10.
Unfallchirurg ; 121(5): 403-412, 2018 May.
Artigo em Alemão | MEDLINE | ID: mdl-29651513

RESUMO

Patients with multiple injuries in particular frequently also suffer from chest trauma. During the initial phase the identification and treatment of life-threatening injuries is essential and tension pneumothorax is of particular importance during this phase. The Advanced Trauma Life Support (ATLS) algorithm should be followed for structured treatment. In most cases treatment by insertion of a chest tube is sufficient but for some injuries an emergency thoracotomy is unavoidable as a life-saving intervention. In the further treatment especially a flail chest and retained hemothorax are responsible for complications, such as acute lung failure and thoracic empyema. Early operative interventions in the sense of rib fracture stabilization and thoracoscopy-assisted evacuation of hematomas can help to prevent such complications.


Assuntos
Pneumotórax , Traumatismos Torácicos , Tubos Torácicos , Hemotórax , Humanos , Pneumotórax/cirurgia , Traumatismos Torácicos/cirurgia , Toracotomia
11.
J Surg Res ; 199(2): 629-34, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26169033

RESUMO

BACKGROUND: The clavicle limits the upper thoracic cage and connects the body and upper extremities. The clavicle is easy to examine and is visible on standard emergency room radiographs. We hypothesized that clavicular fracture in polytrauma patients would indicate the presence of further injuries of the upper extremities, head, neck, and thorax. METHODS: A population-based trauma registry was used. All patients were documented between 2002 and 2013. Inclusion criteria were age ≥16 y and injury severity score (ISS) ≥16. Patients were divided into two groups according to the presence or absence of a clavicular fracture (group C+ and group C-). Scoring was based on the abbreviated injury scale, ISS, and new injury severity score. Trauma mechanisms, demographics, and the posttraumatic clinical course were compared. RESULTS: In total, 4790 patients with clavicular fracture (C+) and 41,775 without (C-) were included; the mean ISS was 30 ± 11 (C+) versus 28 ± 12 (C-). Patients with clavicular fracture had a longer stay on the intensive care unit with 12 ± 14 versus 10 ± 13 d. Injuries to the thoracic wall, severe lung injuries as well as injuries to the cervical spine were significantly increased in C+ patients. Thoracic injuries as well as injuries of the shoulder girdle and/or arm showed an increased abbreviated injury scale in the C+ group. CONCLUSIONS: A clinically relevant coincidence of clavicular fractures with injuries of the chest and upper extremity was found. As clavicular fractures can be diagnosed easily, it might also help to reduce the incidence of missed injuries of the chest and upper extremity. Therefore, special attention should be paid on thoracic as well as upper extremity injures during the second and tertiary surveys in case of clavicular fractures.


Assuntos
Clavícula/lesões , Fraturas Ósseas/diagnóstico por imagem , Traumatismo Múltiplo/diagnóstico por imagem , Sistema de Registros , Traumatismos Torácicos/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia
12.
Mediators Inflamm ; 2015: 132451, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26106256

RESUMO

Impaired fracture healing can occur in severely injured patients with hemorrhagic shock due to decreased soft tissue perfusion after trauma. We investigated the effects of fracture healing in a standardized pressure controlled hemorrhagic shock model in mice, to test the hypothesis that bleeding is relevant in the bone healing response. Male C57/BL6 mice were subjected to a closed femoral shaft fracture stabilized by intramedullary nailing. One group was additionally subjected to pressure controlled hemorrhagic shock (HS, mean arterial pressure (MAP) of 35 mmHg for 90 minutes). Serum cytokines (IL-6, KC, MCP-1, and TNF-α) were analyzed 6 hours after shock. Fracture healing was assessed 21 days after fracture. Hemorrhagic shock is associated with a significant increase in serum inflammatory cytokines in the early phase. Histologic analysis demonstrated a significantly decreased number of osteoclasts, a decrease in bone quality, and more cartilage islands after hemorrhagic shock. µCT analysis showed a trend towards decreased bone tissue mineral density in the HS group. Mechanical testing revealed no difference in tensile failure. Our results suggest a delay in fracture healing after hemorrhagic shock. This may be due to significantly diminished osteoclast recruitment. The exact mechanisms should be studied further, particularly during earlier stages of fracture healing.


Assuntos
Consolidação da Fratura , Choque Hemorrágico/fisiopatologia , Animais , Citocinas/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/fisiologia , Microtomografia por Raio-X
13.
Int Orthop ; 39(5): 947-54, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25690923

RESUMO

INTRODUCTION: Thrombo-embolic events after trauma are considered to be life-threatening complications. Our aim was to determine the incidence of arterial and venous thrombo-embolic events (TE) in severely-injured trauma patients, and its associated risk factors by using a large trauma registry. METHODS: Patients' data from the TraumaRegister DGU® (TR-DGU) were screened for TE (DVT [symptomatic deep vein thrombosis], PE [symptomatic pulmonary embolism], MI [myocardial infarction], and stroke) through the clinical course of severely injured adult trauma patients from January 2005 to December 2012. Univariate analysis was used to compare the clinical outcomes (endpoints: mortality, ICU and hospital length of stay, ventilator days), and a multivariate regression analysis was used to assess the independent risk factors associated with each TE event. RESULTS: From a cohort of 40,846 trauma patients, 1122 (2.8%) patients developed a TE during their post-traumatic clinical course (313, 0.8% DVT; 425, 1.0% PE; 160, 0.4% MI and 231, 0.6% stroke). ICU length of stay [LOS], total LOS, days on mechanical ventilation, and incidence of multiple organ failure (MOF) and sepsis were significantly increased in patients with TE complications. Injury severity, major pelvic injury, and one or more operations were found to be independent risk factors for the development of DVT. Age ≥ 60 years, male gender, and more than one operation were risk factors for PE development. For MI age was the only significant risk factor. The occurrence of a stroke is increased in patients with an age ≥ 60 years, major head injury (AIS head ≥ 3), and more than one operation. Finally, mortality rates were significantly higher in the TE group when compared to the non-TE cohort (21.8% vs. 12.7%; p < 0.001). CONCLUSION: TE complications were associated with longer ICU and hospital stay as well as a higher mortality. Overall, age and repeated operations were the most important risk factors for the development of TE events.


Assuntos
Traumatismo Múltiplo/complicações , Tromboembolia/etiologia , Adulto , Idoso , Feminino , Humanos , Incidência , Escala de Gravidade do Ferimento , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/mortalidade , Sistema de Registros , Respiração Artificial , Fatores de Risco , Tromboembolia/epidemiologia
15.
Calcif Tissue Int ; 95(4): 349-61, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25096517

RESUMO

Oxidative stress plays an important role in wound healing but data relating oxidative stress to fracture healing are scarce. Nuclear factor erythroid 2-related factor 2 (Nrf2) is the major transcription factor that controls the cellular defence essential to combat oxidative stress by regulating the expression of antioxidative enzymes. This study examined the impact of Nrf2 on fracture healing using a standard closed femoral shaft fracture model in wild-type (WT) and Nrf2-knockout (Nrf2-KO)-mice. Healing was evaluated by histology, real-time RT-PCR, µCT and biomechanical measurements. We showed that Nrf2 expression is activated during fracture healing. Bone healing and remodelling were retarded in the Nrf2-KO compared to the WT-mice. Nrf2-KO-mice developed significantly less callus tissue compared to WT-mice. In addition, biomechanical testing demonstrated lower strength against shear stress in the Nrf2-KO-group compared to WT. The expression of vascular endothelial growth factor (VEGF) and osteocalcin is reduced during fracture healing in Nrf2-KO-mice. Taken together, our results demonstrate that Nrf2 deficiency in mice results in impaired fracture healing suggesting that Nrf2 plays an essential role in bone regeneration. Pharmacological activation of Nrf2 may have therapeutic potential for the enhancement of fracture healing.


Assuntos
Consolidação da Fratura , Fator 2 Relacionado a NF-E2/deficiência , Fator 2 Relacionado a NF-E2/genética , Animais , Fenômenos Biomecânicos , Regeneração Óssea , Diferenciação Celular , Condrócitos/citologia , Fêmur/patologia , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteocalcina/metabolismo , Osteoclastos/metabolismo , Estresse Oxidativo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Microtomografia por Raio-X
16.
Unfallchirurgie (Heidelb) ; 127(6): 449-456, 2024 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-38634870

RESUMO

BACKGROUND: Ankle sprains are one of the most frequent injuries of the musculoskeletal system. The injury pattern determines the treatment and are crucial for the outcome. Nonoperative treatment is commonly recommended for isolated injuries of the lateral ligaments but no standard strategy exists in combined ankle ligament injuries. The goal of this national survey was to achieve an overview about the current diagnostic strategies and common treatment concepts in Germany. MATERIAL AND METHODS: All members of the German Society for Orthopaedics and Trauma Surgery (DGOU) were invited to participate in an anonymous survey about the diagnostic and therapeutic approach in cases of ankle sprains. The online survey consisted of 20 questions. Besides questions about the speciality and scope of activities the participants were ask to depict their diagnostic and therapeutic strategy. RESULTS: A total of 806 participants completed the survey. Most of them were orthopedic trauma surgeons and worked in a hospital. During the first presentation the anterior drawer test (89.5%) and the inversion/eversion test (81.6%) were most commonly used, 88.1% always make an X­ray examination and 26.5% an ultrasonography examination. Isolated injuries of the anterior fibulotalar ligament (LFTA) were treated nonoperatively by 99.7% of the participants, 78.8% recommend full weight bearing in an orthesis, 78.8% treat the complete rupture of the lateral ligaments without operation whereas 30.1% stated that they would treat a combined lateral ligaments rupture with an injury of the syndesmosis nonoperatively. DISCUSSION: Due to the heterogeneity of injury patterns after ankle sprain no consistent recommendations for diagnostics and treatment exist. The Ottawa ankle rules and ultrasonography were not often utilized despite of the good evidence. The isolated rupture of the LFTA is diagnosed and treated according to the national guidelines by most of the participants. In cases of combined injuries of the lateral and medial ankle ligaments the majority choose a nonoperative treatment strategy which is justified by the guidelines with a low level of evidence. Combined injuries of the syndesmosis and the lateral ankle ligaments were treated operatively, which also correlates with the recommendations in the literature. The standard care of ankle sprain in Germany is in accordance with the recommendations from the current literature.


Assuntos
Traumatismos do Tornozelo , Traumatismos do Tornozelo/terapia , Traumatismos do Tornozelo/diagnóstico , Traumatismos do Tornozelo/epidemiologia , Humanos , Alemanha , Entorses e Distensões/terapia , Entorses e Distensões/diagnóstico , Entorses e Distensões/epidemiologia , Adulto , Feminino , Inquéritos e Questionários , Masculino , Padrões de Prática Médica/estatística & dados numéricos , Pessoa de Meia-Idade
17.
Hum Brain Mapp ; 34(9): 2217-27, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22461242

RESUMO

Increases in peripheral cytokines during acute inflammation may affect various neuropsychological functions. The aim of this functional magnetic resonance imaging (fMRI) study was to investigate the effects of acute endotoxemia on mood and the neural response to emotionally aversive visual stimuli in healthy human subjects. In a double-blind, randomized crossover study, 18 healthy males received a bolus injection of bacterial lipopolysaccharide (LPS; 0.4 ng/kg) or saline. Plasma levels of pro- and anti-inflammatory cytokines and cortisol as well as mood ratings were analyzed together with the blood-oxygen-level dependent (BOLD) response during the presentation of aversive versus neutral pictures. Endotoxin administration induced pronounced transient increases in plasma levels of TNF-α, IL-1ra, IL-6, IL-10, and cortisol. Positive mood was decreased and state anxiety increased. In addition, activation of right inferior orbitofrontal cortex (OFC) in response to emotional visual stimuli was significantly increased in the LPS condition. Increased prefrontal activation during the presentation of emotional material may reflect enhanced cognitive regulation of emotions as an adaptive response during an acute inflammation. These findings may have implications for the putative role of inflammatory processes in the pathophysiology of depression.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiopatologia , Emoções/fisiologia , Endotoxemia/psicologia , Adulto , Encéfalo/efeitos dos fármacos , Citocinas/sangue , Método Duplo-Cego , Endotoxemia/sangue , Humanos , Hidrocortisona/sangue , Interpretação de Imagem Assistida por Computador , Inflamação/psicologia , Lipopolissacarídeos/toxicidade , Imageamento por Ressonância Magnética , Masculino
18.
Cytokine ; 61(2): 585-90, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23178149

RESUMO

INTRODUCTION: The hemorrhagic shock (HS) model is commonly used to initiate a systemic post-traumatic inflammatory response. Numerous experimental protocols exist and it is unclear how differences in these models affect the immune response making it difficult to compare results between studies. The aim of this study was to compare the inflammatory response of different established protocols for volume-controlled shock in a murine model. METHODS: Male C57/BL6 mice 6-10 weeks and weighing 20-25 g were subjected to volume-controlled or pressure-controlled hemorrhagic shock. In the volume-controlled group 300 µl, 500 µl, or 700 µl blood was collected over 15 min and mean arterial pressure was continuously monitored during the period of shock. In the pressure-controlled hemorrhagic shock group, blood volume was depleted with a goal mean arterial pressure of 35 mmHg for 90 min. Following hemorrhage, mice from all groups were resuscitated with the extracted blood and an equal volume of lactated ringer solution. Six hours from the initiation of hemorrhagic shock, serum IL-6, KC, MCP-1 and MPO activity within the lung and liver tissue were assessed. RESULTS: In the volume-controlled group, the mice were able to compensate the initial blood loss within 30 min. Approximately 800 µl of blood volume was removed to achieve a MAP of 35 mmHg (p<0.001). No difference in the pro-inflammatory cytokine (IL-6 and KC) profile was measured between the volume-controlled groups (300 µl, 500 µl, or 700 µl). The pressure-controlled group demonstrated significantly higher cytokine levels (IL-6 and KC) than all volume-controlled groups. Pulmonary MPO activity increased with the severity of the HS (p<0.05). This relationship could not be observed in the liver. CONCLUSION: Volume-controlled hemorrhagic shock performed following current literature recommendations may be insufficient to produce a profound post-traumatic inflammatory response. A decrease in the MAP following blood withdrawal (300 µl, 500 µl or 700 µl) was usually compensated within 30 min. Pressure-controlled hemorrhagic shock is a more reliable for induction of a systemic inflammatory response.


Assuntos
Inflamação/fisiopatologia , Modelos Biológicos , Choque Hemorrágico/fisiopatologia , Animais , Pressão Sanguínea , Citocinas/sangue , Inflamação/sangue , Inflamação/enzimologia , Inflamação/patologia , Fígado/enzimologia , Fígado/patologia , Fígado/fisiopatologia , Pulmão/enzimologia , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Especificidade de Órgãos , Peroxidase/metabolismo , Choque Hemorrágico/sangue , Choque Hemorrágico/enzimologia , Choque Hemorrágico/patologia
19.
Cytokine ; 63(1): 74-80, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23673286

RESUMO

BACKGROUND AND PURPOSE: Toll like receptor 4 (TLR4) is the major recognition receptor for lipopolysaccharides and plays a major role in the inflammatory response. CD11b is expressed on the surface of many leukocytes including monocytes. The CD11b/CD18 complex is involved in the inflammatory response by mediating migration and adhesion of leukocytes. The aim of this human in vivo study was to investigate the expression of TLR4 and CD11b on the surface of human monocytes after in vivo low-dose LPS stimulation. METHODS: We performed a double-blind, randomized crossover study with 16 healthy males who received a bolus injection of bacterial lipopolysaccharide (LPS; 0.4ng/kg) or normal saline. Vital parameters, blood counts, serum cytokine levels, the expression of TLR4, and CD11b on CD14 positive cells were analyzed. RESULTS: The experimentally induced inflammatory response was reflected by transient increases in body temperature, circulating leukocyte numbers, and plasma levels of pro- (TNF-α, IL-6) and anti-inflammatory cytokines (IL-10, IL-1ra). In contrast to a significant increase in CD11b expression, no changes in TLR4 expression on circulating monocytes were detectable. CONCLUSION: Early changes in TLR4 expression on circulating monocytes are not necessarily part of the inflammatory response to low dose LPS in humans whereas the detected increase of CD11b expression might already be sufficient for optimized recognition and signalling.


Assuntos
Lipopolissacarídeos/farmacologia , Modelos Biológicos , Monócitos/metabolismo , Receptor 4 Toll-Like/metabolismo , Contagem de Células Sanguíneas , Pressão Sanguínea/efeitos dos fármacos , Antígeno CD11b/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Citocinas/sangue , Frequência Cardíaca/efeitos dos fármacos , Humanos , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Monócitos/efeitos dos fármacos
20.
Shock ; 59(3): 486-492, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36533531

RESUMO

ABSTRACT: Objective : The purpose of this study was to investigate the immunomodulatory effects of sulforaphane (SFN), a nuclear factor erythroid 2-related factor (Nrf2) pathway activator, on splenic macrophages' immunocompetence after hemorrhagic shock/resuscitation (HS/R). Methods : Male C57/BL6 wild-type mice (n = 6 per group) were subjected to either pressure-controlled HS (MAP, 35-45 mm Hg) or a sham procedure surgery (without HS). After 90 minutes of HS, fluid resuscitation with withdrawn blood and 0.9% NaCl was performed. Sulforaphane (50 mg/kg of body weight) was applied intraperitoneally immediately after the resuscitation phase as well as 24 and 48 h thereafter, depending on group allocation. The mice were killed at 6, 24, and 72 h after resuscitation. After killing, spleens were harvested to perform Nrf2 immunofluorescence histology. Splenic macrophages were isolated and cultured to measure cytokine secretion in the cell culture supernatant. Furthermore, macrophages isolated after 24-hour resuscitation were treated with 100 ng/mL of bacterial LPS to measure immunocompetence. Matrix-assisted laser desorption/ionization mass spectrometry imaging was performed to verify the distribution of SFN in the spleen after intraperitoneal injection. Results : We showed that administered SFN reached the spleen within the first hour after administration. Furthermore, we identified that SFN increased splenic Nrf2 activation and decreased cytokine expression in splenic macrophages after HS/R. In addition, we showed that SFN exhibited splenic anti-inflammatory properties of macrophages in vitro (IL-6/IL-10-ratio of the HS/R group: 51.79 ± 9.99 [at 6 h] and 15.70 ± 3.35 [at 24 h] vs. HS/R + SFN group: 20.54 ± 5.35 [at 6 h] and 8.60 ± 2.37 [at 24 h], P < 0.05). Furthermore, SFN improved in vitro splenic macrophage immunocompetence after HS/R, as evidenced by the increased secretion of inflammatory cytokines in response to LPS stimulation in vitro . Conclusions : Our study shows that SFN can reduce inflammatory cytokines secreted by splenic macrophages after HS/R and increase their immunocompetence toward a more anti-inflammatory profile.


Assuntos
Citocinas , Choque Hemorrágico , Masculino , Animais , Camundongos , Citocinas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Choque Hemorrágico/patologia , Lipopolissacarídeos , Macrófagos/metabolismo , Anti-Inflamatórios/farmacologia , Ressuscitação
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