Expression of CCR2 by endothelial cells : implications for MCP-1 mediated wound injury repair and In vivo inflammatory activation of endothelium.
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Endothelial cell proliferation and migration may play a central role in angiogenesis, wound healing, and atherosclerosis. Although CXC chemokines can act on endothelial cells by influencing proliferation, an involvement of CC chemokines and endothelial expression of chemokine receptors remains to be elucidated. Reverse transcription-polymerase chain reaction, RNase protection, Western blot, and flow cytometric analysis showed that human umbilical vein endothelial cells express mRNA and surface protein of the monocyte chemotactic protein-1 (MCP-1) receptor CCR2, which was upregulated by inflammatory cytokines. MCP-1 induced migration of endothelial cells in a transwell assay, which was inhibited by the 9-76 MCP-1 receptor antagonist. Increased secretion of MCP-1 or interleukin-8, but not RANTES, on endothelial injury suggested a functional role of CCR2 in wound repair as measured by ELISA. After mechanical injury to endothelial monolayers, which spontaneously closed within 24 hours, wound repair was delayed by the 9-76 antagonist and by a blocking monoclonal antibody to MCP-1, but not to interleukin-8, and was improved by exogenous MCP-1. This was confirmed by quantification of cell migration into the wound area, whereas proliferation and viability were unaltered by MCP-1 or its analogue. Notably, immunohistochemistry of inflamed tissue revealed CCR2 staining on arterial, venous, and venular endothelium affected by cellular infiltration. This is the first demonstration of endothelial CCR2 expression ex vivo, inferring its involvement in inflammatory conditions. Thus endothelial cells express functional CCR2 that may have important implications for endothelial wound repair and inflammatory reactions. (+info)
Kininogens are antithrombotic proteins In vivo.
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Kininogens have recently been shown to possess antiadhesive, anticoagulant, and profibrinolytic properties and can inhibit platelet activation at low thrombin concentrations. To test whether kininogens have antithrombotic properties in vivo, we devised a model of limited arterial injury confined to removal of the endothelium. Brown-Norway Katholiek strain rats with an absence of low- and high-molecular-weight kininogen due to a single point mutation, A163T, were compared in the thrombosis model to the wild-type animals, which were otherwise genetically identical. Despite an equivalent vascular injury, the mean time (+/-SEM) for a 90% decrease in flow measured by laser Doppler was 38.4+/-17 minutes in the kininogen-deficient rats compared with 194+/-29 minutes in the wild-type animals (P<0.002). The degree of vascular injury was the same. No evidence for disseminated intravascular coagulation (decrease in factor V, antithrombin, or fibrinogen) or excessive fibrinolysis (elevation of fibrinogen degradation products) was found in either group of animals. The results suggest that kininogens have antithrombotic properties at low concentrations of thrombin and that inhibitory peptides derived from kininogen may constitute a new antithrombotic strategy. (+info)
Tissue factor pathway inhibitor attenuates procoagulant activity and upregulation of tissue factor at the site of balloon-induced arterial injury in pigs.
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Intravenous infusion of recombinant tissue factor pathway inhibitor (rTFPI) for 24 hours decreases neointimal thickening and luminal stenosis 1 month after balloon-induced injury to the carotid arteries in minipigs. This study was designed to determine whether the effect of rTFPI is accounted for by early decreases in procoagulant activity and thrombosis on the injured vessel wall. Vascular injury was induced by balloon hyperinflations in both carotid arteries of anesthetized pigs given no anticoagulant as a control (n=16), an intravenous infusion for 24 hours of rTFPI (0.5 mg/kg bolus and 25 microg. kg(-1). min(-1), n=14), or an intravenous infusion of unfractionated heparin (100 U. kg(-1). h(-1), n=19). Accumulation of radiolabeled autologous platelets was markedly decreased over 24 hours on injured arteries from animals given rTFPI (0.6x10(6)/cm(2)) compared with controls (2.5x10(6)/cm(2), P=0.0004). Deposition of radiolabeled fibrin was also decreased in rTFPI-treated animals (269+/-266 microg/cm(2)) compared with controls (2389+/-1673 microg/cm(2), P=0.04). Similar effects were observed with heparin. However, factor Xa activity, assayed after 24 hours by incubation of the injured arterial segments with the chromogenic substrate S-2222, was decreased more markedly on arteries from rTFPI-treated animals (0.14+/-0.13 OD) than those from heparin-treated animals (0.29+/-0.18 OD) compared with controls (0. 47+/-0.24 OD, P=0.0007). In addition, arteries from rTFPI-treated animals showed a 4-fold lower induction of tissue factor protein compared with controls (P=0.0002). Attenuation of procoagulant activity and tissue factor-mediated thrombin generation in response to injury may account for the promising results with rTFPI in the porcine angioplasty model. (+info)
The effect of recall on estimation of incidence rates for injury in Ghana.
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BACKGROUND: Injury is a major public health problem in many developing countries. Due to limitations of vital registry and health service data, surveys are an important tool to obtain information about injury in these countries. The value of such surveys can be limited by incomplete recall. The most appropriate recall period to use in surveys on injury in developing countries has not been well addressed. METHODS: A household survey of injury in Ghana was conducted. Estimated annual non-fatal injury incidence rates were calculated for 12 recall periods (1-12 months prior to the interview, with each successively longer period including the preceding shorter periods). RESULTS: There was a notable decline in the estimated rate from 27.6 per 100 per year for a one-month recall period to 7.6 per 100 per year for a 12-month recall period (72% decline). The extent of this decline was not influenced by age, gender, rural versus urban location, nor by type of respondent (in-person versus proxy). Rate of decline was influenced by severity of injury. Injuries resulting in <7 days of disability showed an 86% decline in estimated rates from a one-month to a 12-month recall period, whereas injuries resulting in > or =30 days of disability showed minimal decline. CONCLUSIONS: In this setting, longer recall periods significantly underestimate the injury rate compared to shorter recall periods. Shorter recall periods (1-3 months) should be used when calculating the overall non-fatal injury incidence rate. However, longer recall periods (12 months) may be safely used to obtain information on the more severe, but less frequent, injuries. (+info)
Study of early warning of accident and emergency departments by ambulance services.
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OBJECTIVE: To determine the warning time given to accident and emergency (A&E) departments by the ambulance service before arrival of a critically ill or injured patient. To determine if this could be increased by ambulance personnel alerting within five minutes of arrival at scene. METHODS: Use of computerised ambulance control room data to find key times in process of attending a critically ill or injured patient. Modelling was undertaken with a scenario of the first responder alerting the A&E department five minutes after arrival on scene. RESULTS: The average alert warning time was 7 min (range 1-15 min). Mean time on scene was 22 min (range 4-59 min). In trauma patients alone, the average alert time was 7 min, range 2-15 min, with an average on scene time of 23 min, range 4-53 min. There was a potential earlier alert time averaging 25 min (SD 18.6, range 2-59 min) if the alert call was made five minutes after arrival on scene. CONCLUSIONS: A&E departments could be alerted much earlier by the ambulance service. This would allow staff to be assembled and preparations to be made. Disadvantages may be an increased "alert rate" and wastage of staff time while waiting the ambulance arrival. (+info)
Rollerblading and skateboarding injuries in children in northeast England.
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OBJECTIVES: To establish the demographic profile and injury characteristics of children presenting with rollerblading or skateboarding associated injuries. This study also examines the circumstances leading to these injuries with a view to suggesting preventive measures. METHODS: A prospective study using a proforma to collect data from each child presenting with rollerblading or skateboarding related injuries. Injury details were obtained from clinical and radiological records. The injury severity score (ISS) was calculated for each child and statistical analysis was done using chi2. RESULTS: Eighty one children presented with rollerblading associated injuries accounting for 7% of childhood injuries seen during the eight month study period. The mean age was 10.3 years and sex distribution was equal. Soft tissue injuries accounted for 51% and fractures for 49% of the injuries. Wrist fractures alone accounted for 86% of all fractures seen. Seventy per cent of soft tissue injuries involved the upper limb. The overall mean ISS was 3.0 with a range from 1 to 9. Injury was attributed to fall secondary to loss of control or collision with an obstacle while rollerblading in the majority of children. Injury occurred while rollerblading in residential or public places in 99% of the children. In contrast skateboarding related injuries were much rarer and caused soft tissue injuries only. CONCLUSION: This study has revealed a higher incidence of rollerblading injuries than previously suspected. Effective management strategies should include not only the treatment of these injuries but also attention to their causes and prevention. (+info)
Atraumatic bilateral Achilles tendon rupture: an association of systemic steroid treatment.
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A case of bilateral Achilles tendon rupture associated with steroid use is reported. This case illustrates the importance of taking a thorough drug history in cases of tendon rupture. In lower limb tendon rupture all patients, especially those on steroids, should be warned of the increased risk of contralateral injury. (+info)
IL-1beta mediates induction of hepatic type 1 plasminogen activator inhibitor in response to local tissue injury.
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Type 1 plasminogen activator inhibitor (PAI-1), a major physiological inhibitor of plasminogen activation, is an important component of the hepatic acute phase response. We studied the acute phase regulation of murine hepatic PAI-1 in response to systemic toxicity and local tissue injury in both wild-type mice and in mice in which the interleukin (IL)-1beta gene had been inactivated by gene targeting. Endotoxin induced plasma PAI-1 antigen levels and PAI-1 mRNA accumulation in liver to the same extent in both wild-type and IL-1beta-deficient mice. In contrast, turpentine increased plasma PAI-1 and hepatic PAI-1 mRNA accumulation in wild-type mice but not in IL-1beta-deficient mice. Intraperitoneal injection of murine IL-1beta rapidly increased plasma PAI-1 and hepatic PAI-1 mRNA in both wild-type and IL-1beta-deficient mice. These results suggest that IL-1beta is a critical inducer of hepatic PAI-1 gene expression during the acute phase response to local tissue injury. In situ hybridization studies revealed that hepatocytes are the cells primarily responsible for the hepatic expression of the PAI-1 gene induced by lipopolysaccharide and turpentine. (+info)