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Endothelial Injury (endothelial + injury)
Selected AbstractsEndothelial injury and repair in systemic vasculitis of the youngARTHRITIS & RHEUMATISM, Issue 6 2010L. A. Clarke Objective Endothelial injury is central to the pathogenesis of vasculitis. The purpose of this study was to assess how indices of endothelial injury and repair change during different stages of disease activity in children with primary systemic vasculitis (PSV). Methods Fifty children with PSV, 17 children with nonvasculitic inflammatory diseases (pediatric inflammatory disease controls), 35 healthy age- and sex-matched pediatric controls, and 27 healthy adult controls were included in the study. Biomarkers examined were endothelial microparticles (EMPs), circulating endothelial cells (CECs), angiogenic growth factors, and endothelial progenitor cells (EPCs). EMP binding to annexin V, EMPs expressing CD144 or E-selectin, and EPCs expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34 were examined by flow cytometry. CECs were enumerated using immunomagnetic bead extraction techniques, and VEGF and angiopoietin 2 (Ang-2) were measured by enzyme-linked immunosorbent assay. Results Levels of CD144+ EMPs, CECs, VEGF, and EPCs were all significantly elevated in children with active vasculitis as compared with healthy children, and the levels declined with remission-inducing therapy in the individual patients. Treatment-naive patients with active disease had significantly higher levels of VEGF and Ang-2 than did those with active disease who were receiving treatment, although the levels of CECs and EMPs remained high in both of these groups. Conclusion Elevation of the levels of CECs, EMPS, EPCs, VEGF, and Ang-2 occurs during active vasculitis in children. EPC responses to active vasculitis are different in children as compared with that observed in adults with vasculitis, and both CECs and EMPs can be used to monitor disease activity in children with vasculitis. [source] The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells in T helper 1 immune responsesIMMUNOLOGICAL REVIEWS, Issue 1 2000Shuhji Seki Summary: The liver remains a hematopoietic organ after birth and can produce all leukocyte lineages from resident hematopoietic stem cells. Hepatocytes produce acute phase proteins and complement in bacterial infections. Liver Kupffer cells are activated by various bacterial stimuli, including bacterial lipopolysaccharide (LPS) and bacterial superantigens, and produce interleukin (IL)-12. IL-12 and other monokines (IL-18 etc.) produced by Kupffer cells activate liver natural killer (NK) cells and NK1.1 Ag+ T cells to produce interferon-g and thereby acquire cytotoxicity against tumors and microbe-infected cells. These liver leukocytes and the T helper 1 immune responses induced by them thus play a crucial role in the first line of defense against bacterial infections and hematogenous tumor metastases. However, if this defense system is inadequately activated, shock associated with multiple organ failure takes place. Activated liver NK1.1 Ag+ T cells and NK cells also cause hepatocyte injury. NK1.1 Ag+ T cells and another T-cell subset with an intermediate T-cell receptor, CD122+CD8+ T cells, can develop independently of thymic epithelial cells. Liver NK cells and NK1.1 Ag+ T cells physiologically develop in situ from their precursors, presumably due to bacterial antigens brought from the intestine via the portal vein. NK cells activated by bacterial superantigens or LPS are also probably involved in the vascular endothelial injury in Kawasaki disease. [source] Cigarette smoking, endothelial injury and cardiovascular diseaseINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2000Michael Pittilo Despite the fact that the epidemiological evidence linking cigarette smoking with cardiovascular disease is overwhelming, the precise components of cigarette smoke responsible for this relationship and the mechanisms by which they exert their effect have not yet been elucidated. There are however, some promising pointers as a result of recent developments and this review concentrates on new evidence since earlier reviews of this topic. It is now known that the endothelium has a vastly more important role than was ever thought to be the case a decade ago. Its role in health and disease is increasingly understood, as is the relationship between endothelial injury and the development of atherosclerosis. There is considerable evidence that cigarette smoking can result in both morphological and biochemical disturbances to the endothelium both in vivo and in cell culture systems. Cigarette smoke is a complex mixture and only a few components have been extensively studied. Nicotine and carbon monoxide are much less damaging than is whole smoke. However the free radical components of cigarette smoke have been shown to cause damage in model systems. Further work will be necessary to consolidate the evidence base but the data reported in this review suggest that the free radical components of cigarette smoke may be responsible for the morphological and functional damage to endothelium that has been observed in model systems. [source] Differential availability/processing of decorin precursor in arterial and venous smooth muscle cellsJOURNAL OF ANATOMY, Issue 3 2006Rafaella Franch Abstract The existence of specific differentiation markers for arterial smooth muscle (SM) cells is still a matter of debate. A clone named MM1 was isolated from a library of monoclonal antibodies to adult porcine aorta, which in vivo binds to arterial but not venous SM cells, except for the pulmonary vein. MM1 immunoreactivity in Western blotting involved bands in the range of Mr 33,226 kDa, in both arterial and venous SM tissues. However, immunoprecipitation experiments revealed that MM1 bound to a 100-kDa polypeptide that was present only in the arterial SM extract. By mass spectrometry analysis of tryptic digests from MM1-positive 130- and 120-kDa polypeptides of aorta SM extract, the antigen recognized by the antibody was identified as a decorin precursor. Using a crude decorin preparation from this tissue MM1 reacted strongly with the 33-kDa polypeptide and this pattern did not change after chondroitinase ABC treatment. In vitro, decorin immunoreactivity was found in secreted grainy material produced by confluent arterial SM cells, although lesser amounts were also seen in venous SM cells. Western blotting of extracts from these cultures showed the presence of the 33-kDa band but not of the high-molecular-weight components, except for the 100-kDa monomer. The 100/33-kDa combination was more abundant in arterial SM cells than in the venous counterpart. In the early phase of neointima formation, induced by endothelial injury of the carotid artery or vein-to-artery transposition, the decorin precursor was not expressed, but it was up-regulated in the SM cells of the media underlying the neointima in both models. Collectively, these data suggest a different processing/utilization of the 100-kDa monomer of proteoglycan decorin in arterial and venous SM cells, which is abolished after vein injury. [source] Endothelial Progenitor Cells: A Promising Therapeutic Alternative for Cardiovascular DiseaseJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 2 2007CHUNMING DONG The integrity and functional activity of the endothelial monolayer play a critical role in preventing atherosclerotic disease progression. Endothelial cell (EC) damage by atherosclerosis risk factors can result in EC apoptosis with loss of the integrity of the endothelium. Thus, approaches to repair the injured vessels with the goal of regenerating ECs have been tested in preclinical experimental models and in clinical studies. Indeed, endothelial progenitor cells (EPCs) originating from the bone marrow have been shown to incorporate into sites of neovascularization and home to sites of endothelial denudation. These cells may provide an endogenous repair mechanism to counteract ongoing risk factor-induced endothelial injury and to replace dysfunctional endothelium. Risk factors for coronary artery disease, such as age, smoking, hypertension, hyperlipidemia, and diabetes, however, reduce the number and functional activity of circulating EPCs, potentially restricting the therapeutic prospective of progenitor cells and limiting the regenerative capacity. Furthermore, the impairment of EPCs by risk factors may contribute to atherogenesis and atherosclerotic disease progression. The article reviews the role of EPCs in atherogenesis and in predicting cardiovascular outcomes, and highlights the potential challenges in developing therapeutic strategies aiming to interfere with the balance of injury and repair mechanisms. [source] Melatonin prevents lipopolysaccharide-induced hyporeactivity in ratJOURNAL OF PINEAL RESEARCH, Issue 3 2004Roberta D'Emmanuele Di Villa Bianca Abstract:, Melatonin (MT) is the principal secretory product of the pineal gland and its role as an immumo-modulator is well established. Recent evidence shows that MT exerts protective effects in septic shock, hemorrhagic shock and inflammation. Lipopolysaccharide (LPS), from Escherichia coli, administered to animals directly stimulates a number of cells and systems to produce various inflammatory mediators. LPS-induced septic shock is characterized by hypotension and vascular hyporeactivity to contracting agents. In particular, the reactive oxygen species such as superoxide and nitric oxide (NO) contribute to the pathophysiology of septic shock. In this study, we demonstrate that MT pretreatment prevents the hyporeactivity to phenylephrine in vivo and in aorta rings collected from rats treated with the endotoxin. The beneficial effect of MT seems related to its antioxidant properties and with inhibition of inducible nitric oxide synthase (iNOS) protein expression, reduction of NO production and nitrotyrosine formation, in aorta, preventing vascular, and endothelial injury. Additionally, we first demonstrate, that MT inhibited nuclear enzyme poly (ADP-ribose) synthetase activation in vascular tissue. The current study underlined the protective effect of MT on the vascular dysfunction associated with septic shock, data that could support the clinical use of MT in human endotoxemia. [source] ,2 -Antiplasmin plays a significant role in acute pulmonary embolismJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2003H. Matsuno Summary., The importance of pulmonary embolism (PE) due to venous thrombosis is recognized in the treatment of vascular diseases. We have investigated the physiological effects of plasmin generation in experimental acute PE using mice deficient in plasminogen (Plg,/,) or ,2 -antiplasmin (,2 -AP,/,). PE was induced by continuous induction of venous thrombus in the left jugular vein by endothelial injury due to photochemical reaction. The mortality of wild-type mice was 68.8% at 2 h after the initiation of venous thrombosis and it was significantly reduced in ,2 -AP,/, mice (41.7%). In contrast, Plg,/, mice did not survive. Histological evidence of thromboembolism in the lung was obtained in all mice. However, whereas a strict thromboembolism was observed in Plg,/, mice, only a few thrombi were detected in the lungs of ,2 -AP,/, mice. Plasma fibrinogen levels measured in mice were not different. When ,2 -AP was infused in ,2 -AP,/, mice, the mortality was indistinguishable from wild-type mice. Tissue-type plasminogen activator (tPA) did not reduce the mortality due to acute PE in wild-type mice. However, in ,2 -AP,/, mice, tPA (0.52 mg kg,1) significantly decreased the mortality compared with that of ,2 -AP,/, mice without tPA. The bleeding time was not significantly prolonged in either type of mice treated with tPA. The lack of plasminogen increases the mortality due to acute PE while a lack of ,2 -AP decreases the mortality rate, which can be further reduced by tPA administration. Therefore, the combination of inhibition of ,2 -AP with thrombolytic therapy could be beneficial in the treatment of acute PE. [source] Prospective study of the A455V polymorphism in the thrombomodulin gene, plasma thrombomodulin, and incidence of venous thromboembolism: the LITE StudyJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2003N. Aleksic Summary., Plasma thrombomodulin (soluble TM; sTM) is considered to be a marker of endothelial injury, but a recent report indicated that the relationship of sTM with thrombosis is complex. Venous thromboembolic events were identified in adults in two longitudinal cohort studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, totaling 21 690 participants. After 8 years of follow-up, sTM was measured in baseline plasma of 305 participants who developed venous thrombosis and 607 who did not. Thrombomodulin A455V genotype was determined in 302 cases and 626 controls. There was no difference in the prevalence of the three TM genotypes between cases and controls and no difference in age-adjusted mean values of sTM by genotype. There were no associations of age-adjusted sTM or TMA455V genotype with overall venous thromboembolism or with thrombosis in any subtype of venous thromboembolism. [source] Cholestatic liver disease: pathophysiology and therapeutic optionsLIVER INTERNATIONAL, Issue 2002AF. Hofmann Abstract: Cholestasis results from defective canalicular secretion of bile or obstruction to bile flow distal to the canaliculus. In early primary biliary cirrhosis, bile secretion continues, because of the secretory pressure of bile or because some ductules are not obstructed. With complete cholestasis, a bile acid deficiency occurs in the small intestinal lumen leading to lipid maldigestion and fat-soluble vitamin malabsorption. Bacterial proliferation, bacterial translocation to lymph nodes and endotoxemia may also occur leading to an acute phase reaction. Retention of bile acids in the hepatocyte leads to apoptosis. Accumulation of bile acids in the systemic circulation leads to pruritus, and may contribute to endothelial injury in the lungs and kidney. Early attempts to mimic hepatic excretory function by hemoperfusion over adsorbent columns were unsuccessful for a variety of reasons. Extracorporeal dialysis against albumin offers promise of a realistic albeit partial simulation of hepatic excretory function. [source] Alteration of urothelial-mediated tone in the ischemic bladder: Role of eicosanoids,NEUROUROLOGY AND URODYNAMICS, Issue 3 2004Kazem M. Azadzoi Abstract Aims Previously we showed that ischemia alters bladder smooth muscle contractility in the rabbit. This study investigates the role of urothelium and eicosanoid-release in ischemic bladder smooth muscle instability. Materials and Methods Male New Zealand white rabbits were divided into treated (n,=,12) and age-matched control (n,=,10) groups. The treated group underwent balloon endothelial injury of the iliac arteries, and then received 4 weeks of cholesterol diet, followed by 4 weeks of regular diet. The control group received a regular diet for 8 weeks. After 8 weeks, blood flow for both the iliac arteries and the bladder as well as bladder oxygen tension were recorded. In one-half of each ischemic and control bladder, the urothelium was removed. Bladder tissues were processed for organ bath and enzyme-immunoassay (EIA) of prostaglandins (PGs) and leukotrienes (LTs). Results A significant decrease in iliac arterial blood flow, bladder wall blood flow, and bladder oxygen tension was found in the treated group. Bladder ischemia increased the frequency and amplitude of baseline spontaneous smooth muscle contractility. Ischemic tissues with urothelium (Uro+) demonstrated significant increases in the contractile response to electrical field stimulation (EFS) and carbachol relative to control Uro+ tissues. Urothelial removal increased smooth muscle contraction in the control tissues but had no significant effect in the ischemic/hypoxic tissues. Contraction of control tissues without urothelium (Uro,) was similar to contraction of ischemic Uro+ tissues. Contractions of ischemic Uro+ and control Uro, tissues were unchanged after treatment with the cyclooxygenase (COX) inhibitor indomethacin, while they were significantly reduced by the 5-lipoxygenase (5-LO) inhibitor NDGA. EIA showed no change in PGs release from the ischemic urothelium, but significant increase in PGF2-, and thromboxane A2 release from the ischemic suburothelial tissue. Ischemia increased the release of LTB4, LTC4, and LTE4 from both urothelium and suburothelial tissue. Conclusions Our studies suggest loss of urothelial-mediated tone and LTs-mediated smooth muscle instability in the chronically ischemic/hypoxic bladder. Neurourol. Urodynam. 23:258,264, 2004. Published 2004 Wiley-Liss, Inc. [source] NK Cell Transcripts and NK Cells in Kidney Biopsies from Patients with Donor-Specific Antibodies: Evidence for NK Cell Involvement in Antibody-Mediated RejectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010L. G. Hidalgo To explore the mechanisms of antibody-mediated rejection (ABMR) in kidney transplants, we studied the transcripts expressed in clinically indicated biopsies from patients with donor-specific antibody (DSA). Comparison of biopsies from DSA-positive versus DSA-negative patients revealed 132 differentially expressed transcripts: all were associated with class II DSA but none with class I DSA. Many transcripts were expressed in DSA-positive ABMR but were also expressed in T-cell-mediated rejection (TCMR), reflecting shared molecular features. Removal of shared transcripts created 23 DSA selective transcripts (DSASTs). Some DSASTs (6/23) showed selective high expression in NK cells, whereas others (8/23) were expressed in endothelium or in endothelium plus other cell types (7/23). Of 145 biopsies ranked by DSAST expression, the 25 with highest DSAST expression primarily consisted of ABMR (22/25, 88%), either C4d-positive or C4d-negative. By immunostaining, CD56+ and CD68+ cells in peritubular capillaries, but not CD3+ cells, were increased in ABMR compared to TCMR, compatible with a role for NK cells, as well as macrophages, as effectors in endothelial injury during ABMR. Thus, the strategy of using DSASTs in the biopsy to identify mechanism-related transcripts in biopsies from patients with clinical phenotypes indicates the selective involvement of NK cells in ABMR. [source] Peritubular Capillary Damage in Acute Humoral Rejection: An Ultrastructural Study on Human Renal AllograftsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2005P. Lipták The ultrastructural features of peritubular capillary (PC) damage was studied in 12 kidney allografts with acute humoral rejection (AHR). AHR manifested in diffuse linear PC staining for C4d, and histology consistent with Banff grade III in 7 recipients and Banff grade II in 5. Allografts with acute tubular necrosis served as controls. First biopsies (post-transplantation day 16.2 ± 2.2): The intra-capillary exudate comprised monocytes (59%), polymorphonuclears (14%), lymphocytes (12%) and not otherwise specified mononuclears (15%). Three patterns of focal PC endothelial injury were observed: lysis, an increased rate of apoptosis and fragmentation. No correlation was found between the respective damage types and the inflammatory cell types or the Banff grades. Controls revealed endothelial swelling, detachment from basement membrane and fragmentation. Follow-up biopsies: Monocytes transformed into macrophages intra-luminally. The reparative changes comprised endothelial cytoplasmic protrusions, binucleated endothelial cells and capillary sprouts. Early transplant capillaropathy and transplant glomerulopathy were noted in 2 recipients. Literature data indicate that lysis is mediated by anti-HLA alloantibodies; apoptosis, demonstrated first in the present study, may be induced by non-HLA-type anti-endothelial antibodies. Fragmentation is caused by ischemia. Ongoing endothelial injury leads to transplant capillaropathy and transplant glomerulopathy, the characteristic lesions of chronic rejection. [source] Endothelial injury and repair in systemic vasculitis of the youngARTHRITIS & RHEUMATISM, Issue 6 2010L. A. Clarke Objective Endothelial injury is central to the pathogenesis of vasculitis. The purpose of this study was to assess how indices of endothelial injury and repair change during different stages of disease activity in children with primary systemic vasculitis (PSV). Methods Fifty children with PSV, 17 children with nonvasculitic inflammatory diseases (pediatric inflammatory disease controls), 35 healthy age- and sex-matched pediatric controls, and 27 healthy adult controls were included in the study. Biomarkers examined were endothelial microparticles (EMPs), circulating endothelial cells (CECs), angiogenic growth factors, and endothelial progenitor cells (EPCs). EMP binding to annexin V, EMPs expressing CD144 or E-selectin, and EPCs expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34 were examined by flow cytometry. CECs were enumerated using immunomagnetic bead extraction techniques, and VEGF and angiopoietin 2 (Ang-2) were measured by enzyme-linked immunosorbent assay. Results Levels of CD144+ EMPs, CECs, VEGF, and EPCs were all significantly elevated in children with active vasculitis as compared with healthy children, and the levels declined with remission-inducing therapy in the individual patients. Treatment-naive patients with active disease had significantly higher levels of VEGF and Ang-2 than did those with active disease who were receiving treatment, although the levels of CECs and EMPs remained high in both of these groups. Conclusion Elevation of the levels of CECs, EMPS, EPCs, VEGF, and Ang-2 occurs during active vasculitis in children. EPC responses to active vasculitis are different in children as compared with that observed in adults with vasculitis, and both CECs and EMPs can be used to monitor disease activity in children with vasculitis. [source] Independent association of anti,,2 -glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patientsARTHRITIS & RHEUMATISM, Issue 8 2009Francesco Boin Objective Systemic sclerosis (SSc; scleroderma) is characterized by a unique widespread vascular involvement that can lead to severe digital ischemia, pulmonary arterial hypertension (PAH), or other organ dysfunction. Microthrombotic events and procoagulation factors such as anti,,2-glycoprotein I (anti-,2GPI) or anticardiolipin antibodies (aCL) may be implicated in the development of these manifestations. This study was undertaken to investigate whether anti-,2GPI and aCL are correlated with macrovascular disease, including ischemic digital loss and PAH, in SSc patients. Methods Seventy-five SSc patients with a history of ischemic digital loss and 75 matched SSc controls were evaluated. Anticentromere antibodies (ACAs), anti-,2GPI, and aCL were measured, and clinical associations were determined using conditional and simple logistic regression models. Results Positivity for anti-,2GPI was significantly more frequent in SSc patients with digital loss than in patients without digital loss (P = 0.017), with the IgA isotype of anti-,2GPI showing the strongest association (odds ratio [OR] 4.0). There was no significant difference in aCL frequency between patients with digital loss and control patients. After adjustment for demographic characteristics, disease type, smoking, and ACA, anti-,2GPI positivity was significantly associated with active digital ischemia (OR 9.4), echocardiographically evident PAH (OR 4.8), and mortality (OR 2.9). ACA positivity was associated with history of digital loss (OR 3.28), but not with PAH or mortality. History of digital loss was strongly associated with increased mortality (OR 12.5). Conclusion Anti-,2GPI is significantly associated with macrovascular disease in SSc and independently predicts mortality. It is unclear whether it has a pathogenetic role or simply reveals the presence of underlying endothelial injury. The use of anti-,2GPI as a biomarker of vascular disease in SSc should be further explored. [source] Activated protein C levels in Behçet's disease and risk of venous thrombosisBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2004Silvia Navarro Summary Behçet's disease is a multi-systemic inflammatory disorder of unknown cause. Most abnormalities have been associated with endothelial injury caused by vasculitis. Thrombosis occurs in about 25% of patients, although the mechanism is unknown. The objective of this study was to evaluate the protein C activation system in Behçet's disease and its correlation with venous thromboembolism (VTE). Thirty-nine patients (12 with VTE) and 78 age- and sex-matched controls were included in the study, and levels of protein C, protein S, activated protein C (APC), protein C inhibitor (PCI), soluble thrombomodulin (TM), antithrombin (AT), ,1 -antitrypsin, fibrinogen, factor VIII, von Willebrand factor (VWF) and C-reactive protein (CRP) were measured. APC and TM levels were significantly lower in patients than in controls, whereas protein S, AT, ,1 -antitrypsin, fibrinogen, factor VIII, VWF and CRP levels were significantly higher in patients than in controls. APC, PCI and TM levels were lower in patients with VTE (0·65 ± 0·19 ng/ml, 86% ± 22% and 15·5 ± 7·1 ng/ml respectively) than in those without VTE (0·78 ± 0·17 ng/ml, 100% ± 15% and 22·1 ± 15·3 ng/ml) (P < 0·05). In patients, APC levels below 0·75 ng/ml (10th percentile of the control group) increased the risk of VTE about fivefold (odds ratio = 5·1; 95% confidence interval = 1·1,23·4). These results show that reduced APC levels are associated with the high incidence of VTE in Behçet's disease. [source] The interaction between components of the fibrinolytic system and GPIb/V/IX of platelets thrombus formation in miceBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2000Hiroyuki Matsuno The interaction of fibrinolytic components with GPIb/V/IX of platelets on thrombus formation, was investigated in mice deficient in tissue type (tPA,/,), urokinase type plasminogen activator (uPA,/,) or plasminogen activator inhibitor-1 (PAI-1,/,) and in their wild type control (tPA+/+, uPA+/+, PAI-1+/+). A thrombus was induced in the murine carotid artery using a photochemical reaction. The times to occlusion after the initiation of endothelial injury in all wild type mice was within 12 min, and no significant changes in occlusion delay were observed in uPA,/, and tPA,/, mice compared to wild type mice, whereas that of PAI-1 mice were significantly prolonged (16.9±2.9 min, P<0.05). When high molecular weight aurintricarboxylic acid (ATA), an inhibitor of platelet glycoprotein Ib/V/IX, was administered, the time to occlusion was prolonged in a dose-dependent manner in all types of mice. However, when this compound was injected in tPA,/, mice, the most significant changes were observed: i.e. the estimated ED50 was 20.2 times higher than that in tPA+/+ mice, but the estimated ED50 in uPA,/, mice was not changed as compared with that of wild type mice. On the other hand, when ATA was injected in PAI-1,/, mice, the estimated ED50 was significantly decreased (P<0.05). Platelet aggregation induced by botrocetin was not significantly different among all types of mice. The bleeding time was prolonged in a dose dependent-manner when ATA was injected in all types of mice. In conclusion, the antithrombotic effect of inhibition of platelet GPIb/V/IX is severely affected by the absence or presence of tPA-production on thrombus formation and the inhibition of PAI-1 could enhance this antithrombotic effect. British Journal of Pharmacology (2000) 131, 858,864; doi:10.1038/sj.bjp.0703639 [source] Iatrogenic vertebral artery injuryACTA NEUROLOGICA SCANDINAVICA, Issue 6 2005J. Inamasu Iatrogenic vertebral artery injury (VAI) results from various diagnostic and therapeutic procedures. The objective of this article is to provide an update on the mechanism of injury and management of this potentially devastating complication. A literature search was conducted using PubMed. The iatrogenic VAIs were categorized according to each diagnostic or therapeutic procedure responsible for the injury, i.e., central venous catheterization, cervical spine surgery, chiropractic manipulation, diagnostic cerebral angiography, percutaneous nerve block, and radiation therapy. The incidence, mechanisms of injury, and reparative procedures were discussed for each type of procedure. The type of VAI depends largely on the type of procedure. Laceration was the dominant type of acute injury in central venous catheterization and cervical spine surgery. Arteriovenous fistulae and pseudoaneurysms were the delayed complications. Arterial dissection was the dominant injury type in chiropractic manipulation and diagnostic cerebral angiography. Inadvertent arterial injection caused seizures or stroke in percutaneous nerve block. Radiation therapy was responsible for endothelial injury which in turn resulted in delayed stenosis and occlusion of the vertebral artery (VA). The proximal VA was the most vulnerable portion of the artery. Although iatrogenic VAIs are rare, they may actually be more prevalent than had previously been thought. Diagnosis of iatrogenic VAI may not always be easy because of its rarity and deep location, and a high level of suspicion is necessary for its early detection. A precise knowledge of the surgical anatomy of the VA is essential prior to each procedure to prevent its iatrogenic injury. [source] Comparison of the corneal endothelial protective effects of Healon-D and ViscoatCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 4 2009Carolee M Cutler Peck MD MPH Abstract Background:, The use of dispersive ophthalmic viscosurgical devices (OVDs) has been shown to provide significant protection against air bubble damage to the corneal endothelium when compared with cohesive OVDs. We compared the corneal endothelial protective effects of a new dispersive OVD, Healon-D, with Viscoat. Methods:, Healon-D and Viscoat were used in a randomized and masked fashion in the anterior chamber of 40 rabbit eyes during a procedure where ultrasound at 70% continuous energy was delivered for 2 min. Two millilitres of air bubbles were injected into the anterior chamber during the first minute of the procedure on each eye. Corneas were then stained with trypan blue and alizarin red and evaluated via light microscopy for endothelial injury. Both denuding of the endothelial layer, as well as damage to endothelial cells were quantified by using the Evaluation of Posterior Capsule Opacification digital imaging system. Results:, The denuded area for eyes treated with Healon-D and Viscoat were not significantly different (medians of 0.004167and 0.003333, respectively, P = 0.8908). There was no significant difference in the area of endothelial cell damaged (medians of 0.02183 and 0.01433, respectively, P = 0.4565). When the denuded and damaged areas were calculated together, there was also no difference in the total injured area (medians of 0.05817 and 0.05821, respectively, P = 0.5740). Conclusion:, The new dispersive OVD Healon-D is equally as effective as Viscoat in protecting the corneal endothelial layer from denuding and damage from air bubbles during anterior segment surgery. [source] Morphological and biochemical effects of immunosuppressive drugs in a capillary tube assay for endothelial dysfunctionCLINICAL TRANSPLANTATION, Issue 2003Chumpon Wilasrusmee Abstract: Immunosuppressive drugs common in clinical transplantation are known to have untoward effects on the vascular system. The effects of some drugs, notably cyclosporin A (CyA), have been studied on the vascular system, while those of others have not. In the vascular system, endothelial cells are the predominant cell type exposed to intravascular concentrations of immunosuppressive drugs. We therefore studied the effects of drugs common in clinical transplantation on endothelial cells in a capillary tube assay. The endothelial cells in the capillary tubes are morphologically more similar to those in the microvasculature than endothelial cells in monolayers. We studied the kinetics and extent of capillary tube formation and prostacyclin (PGI2) and endothelin-1 (ET-1) release from the in vitro capillaries to determine the morphological and biochemical effects of five immunosuppressive agents on endothelial function. We found a significant difference in the morphological and biochemical effects of the two common calcineurin inhibitors, CyA and tacrolimus (FK506) on capillary morphology in vitro. The former had a pronounced injurious effect on the morphology of the in vitro capillaries, while the latter did not. CyA also significantly increased ET-1 release by the capillaries, but FK506 did not. Mycophenolate mofetil (MMF) was the only other agent that had a moderately injurious effect on the morphology of the in vitro capillaries. Sirolimus (rapamycin) and dexamethasone, similar to FK506, had no effect on the capillary morphology. All these agents, except dexamethasone, increased PGI2 release. Our data suggest that CyA adversely affects the morphology of the microvasculature and that this is mediated, at least partly, by an increased ET-1 release by endothelial cells exposed to CyA. These findings describe a novel effect of CyA and MMF on endothelial cells that could be relevant to understanding the mechanisms of immunosuppressive drug-mediated endothelial injury in clinical transplantation. [source] Reversible brain lesions in childhood hypertensionACTA PAEDIATRICA, Issue 9 2002P Singhi Posterior leukoencephalopathy syndrome is characterized by an acute, usually reversible, encephalopathy with transient occipital lobe abnormalities detected on MRI that occur mostly in association with acute hypertension. The clinical presentation includes seizures, headache, altered mental status and blindness. Disturbed autoregulation of cerebral blood flow and endothelial injury are central to the pathogenesis of this disorder. Prompt control of hypertension results in rapid and complete neurological recovery. In this report we discuss the cases of two children with acute onset hypertension of different aetiologies that presented with the characteristic features of posterior leukoencephalopathy syndrome. Conclusion: Early recognition of this readily treatable condition may obviate the need for extensive and invasive investigations. Despite the alarming lesions on the MRI, prompt control of hypertension carries a uniformly favourable prognosis. [source] | |||||||||||||