Home About us Contact
|
Home About us Contact | ||
|
|
||
Vascular Permeability (vascular + permeability)
Kinds of Vascular Permeability Selected AbstractsEffects of aging and HIF-1, deficiency on permeability of hippocampal vesselsMICROSCOPY RESEARCH AND TECHNIQUE, Issue 1 2006Masaki Ueno Abstract We examined age-related changes in the blood,brain barrier (BBB) of neural cell-specific hypoxia inducible factor-1, (HIF-1,) deficient mice, which showed hydrocephalus with neuronal cell loss, to investigate an effect of neural cell-specific HIF-1, deficiency or hydrocephalus on vascular function. Vascular permeability of horseradish peroxidase (HRP) and binding of cationized ferritin (CF) particles to the endothelial cell luminal surface, as a marker of glycocalyx, were investigated. The thickness of CF-labeled glycocalyx was significantly decreased in the cortex in mutant mice compared with that of control mice, although it was not paralleled by increased vascular permeability. In addition, strong staining for HRP was seen around vessels located along the hippocampal fissure in 24-month-old mutant mice. The reaction product of HRP appeared in an increasing number of the endothelial cell abluminal vesicles and within the thickened basal lamina of arterioles in the hippocampus, showing increased vascular permeability. There were no leaky vessels in 10-week-old mutant mice or 10-week-old and 24-month-old control mice. These findings suggest the necessity of two factors, aging and hydrocephalus, for BBB dysfunction in HIF-1, deficient mice. Microsc. Res. Tech. 69:29,35, 2006. © 2006 Wiley-Liss, Inc. [source] Cytosolic Ca2+ concentration and rate of increase of the cytosolic Ca2+ concentration in the regulation of vascular permeability in Rana in vivoTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005C. A. Glass Vascular permeability is assumed to be regulated by the cytosolic Ca2+ concentration ([Ca2+]c) of the endothelial cells. When permeability is increased, however, the maximum [Ca2+]c appears to occur after the maximum permeability increase, suggesting that Ca2+ -dependent mechanisms other than the absolute Ca2+ concentration may regulate permeability. Here we investigate whether the rate of increase of the [Ca2+]c (d[Ca2+]c/dt) may more closely approximate the time course of the permeability increase. Hydraulic conductivity (Lp) and endothelial [Ca2+]c were measured in single perfused frog mesenteric microvessels in vivo. The relationships between the time courses of the increased Lp, [Ca2+]c and d[Ca2+]c/dt were examined. Lp peaked significantly earlier than [Ca2+]c in all drug treatments examined (Ca2+ store release, store-mediated Ca2+ influx, and store-independent Ca2+ influx). When Lp was increased in a store-dependent manner the time taken for Lp to peak (3.6 ± 0.9 min during store release, 1.2 ± 0.3 min during store-mediated Ca2+ influx) was significantly less than the time taken for [Ca2+]c to peak (9.2 ± 2.8 min during store release, 2.1 ± 0.7 min during store-mediated influx), but very similar to that for the peak d[Ca2+]c/dt to occur (4.3 ± 2.0 min during store release, 1.1 ± 0.5 min during Ca2+ influx). Additionally, when the increase was independent of intracellular Ca2+ stores, Lp (0.38 ± 0.03 min) and d[Ca2+]c/dt (0.30 ± 0.1 min) both peaked significantly before the [Ca2+]c (1.05 ± 0.31 min). These data suggest that the regulation of vascular permeability by endothelial cell Ca2+ may be regulated by the rate of change of the [Ca2+]c rather than the global [Ca2+]. [source] Effect of Inhibitor of Tumor Necrosis Factor-, and Oxatomide on Immune Mediated Otitis MediaTHE LARYNGOSCOPE, Issue 9 2006Yong-Soo Park MD Abstract Objective: Inflammatory mediators (IMs) play a major role in the production of middle ear effusion (MEE). Tumor necrosis factor (TNF)-, and leukotrienes (LTs) appear to be important in the pathogenesis of otitis media with effusion (OME). The purpose of this study is to determine the effect of TNF-, and LT antagonist on the outcome of experimental immune-mediated OME. Study Design: Prospective. Methods: Otitis media was induced in rats by injecting keyhole limpet hemocyanin (KLH) transtympanically 7 days after systemic immunization. Experimental groups were treated with soluble TNF receptor type I (sTNF RI) or oxatomide simultaneously. Seventy-two hours after transtympanic injection, MEE was aspirated, and temporal bone was taken. Vascular permeability (VP) of the middle ear mucosa was measured using the Evans blue dye technique. Hematoxylin-eosin stain and immunohistochemical stain for leukocyte common antigen was performed. Results: In KLH, sTNF RI, and oxatomide groups, MEE was developed in 83%, 0%, and 66% of the ears, respectively. The sTNF RI group showed significant decrease in effusion production, inflammation, mucosal thickening, and VP compared with the KLH group. These parameters were less significant in the oxatomide group than in the sTNF RI group. Conclusion: Transtympanic administration of sTNF RI and oxatomide appears to suppress the development of immune-mediated MEE. [source] Non-viral gene therapy for diabetic retinopathyDRUG DEVELOPMENT RESEARCH, Issue 11 2006*Article first published online: 9 FEB 200, Toshiyuki Oshitari Abstract Diabetic retinopathy results from vascular abnormalities, such as an increase in the permeability of retinal vessels, and retinal neurodegeneration, which are irreversible changes that occur early in the course of diabetic retinopathy. To block the vascular and neuronal complications associated with the development and progression of diabetic retinopathy, a reasonable strategy would be to prevent the increased vascular permeability and to block the neuronal cell death. The purpose of this review is to present the non-viral strategies being used to block the neurovascular abnormalities and neuronal cell death that are observed in the early stages of diabetic retinopathy in order to prevent the onset or the progression of the diabetic retinopathy. Some of the non-viral gene therapeutic techniques being used are electroporation of selected genes, injections of antisense oligonucleotides, and injections of small interference RNAs. The results obtained by these methods are discussed as is the potential of these therapeutic strategies to prevent the onset or the progression of the neurovascular abnormalities in diabetic retinopathy. Drug Dev. Res. 67:835,841, 2006. © 2007 Wiley-Liss, Inc. [source] Vascular endothelial growth factor gene polymorphisms are associated with the risk of developing adenomyosisENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2009Shan Kang Abstract Vascular endothelial growth factor (VEGF), a major mediator of angiogenesis and vascular permeability, may play a key role in the development of adenomyosis. The aim of this study was to investigate whether these four VEGF polymorphisms (,2578C/A, ,1154G/A, ,460C/T, and +936C/T) were associated with the risk of adenomyosis development. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 174 adenomyosis patients and 199 frequency-matched control women. There were significant differences between patients and control group in allele frequencies and genotype distributions of the ,2578C/A polymorphisms (P = 0.010 and 0.044, respectively). Compared with the C/C genotype, the A/A + C/A genotype could significantly modify the risk of developing adenomyosis [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.42,0.97]. For the ,1154G/A polymorphism, the allele frequencies and genotype distributions in patient group were significant different from those of the controls (P = 0.001 and 0.007, respectively). Compared with the G/G genotype, the A/A + G/A genotype could significantly decrease the risk of developing adenomyosis (OR = 0.51, 95% CI = 0.33,0.80). However, the genotype distributions and allele frequencies of the ,460C/T and +936C/T polymorphisms did not significantly differ between controls and patients (all P value > 0.05). The haplotype analysis suggested that the TGA (VEGF ,460/,1154/,2578) and CGA haplotypes exhibited a significant decrease in the risk of developing adenomyosis compared with the haplotype of TGC (OR = 0.64, 95% CI = 0.41,1.00; OR = 0.44, 95% CI = 0.21,0.93, respectively). The study indicated that the ,2578A or ,1154A allele of VEGF gene could significantly decrease the risk of adenomyosis and might be potentially protective factors for adenomyosis development. Environ. Mol. Mutagen., 2009. © 2009 Wiley-Liss, Inc. [source] Potential role of soluble angiopoietin-2 and Tie-2 in patients with inflammatory bowel diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2006I. E. Koutroubakis Abstract Background, Angiogenesis has been suggested to play an important role in inflammatory bowel disease (IBD). The aim of the study was to evaluate the serum markers of angiogenesis angiopoietin-2 (Ang-2) and soluble angiopoietin receptor Tie-2 in patients with ulcerative colitis (UC) and Crohn's disease (CD). Materials and methods, Serum Ang-2 and Tie-2 serum levels were measured in 160 IBD patients (79 UC and 81 CD) and in 80 matched healthy controls using commercially available enzyme-linked immunosorbent assays. Serum Ang-2 and Tie-2 levels were correlated with the disease activity, as well as the type, localization and treatment of the disease. Results, Median serum Ang-2 and Tie-2 levels were significantly higher in both the UC patients and the CD patients compared with the healthy controls (P < 0·05 and P < 0·001, respectively). The IBD patients with early disease (diagnosis < 2 years) had significantly higher (P = 0·04) median serum Ang-2 levels but significantly lower (P = 0·02) median serum Tie-2 levels as compared with IBD patients with late disease (diagnosis > 2 years). The CD patients with active disease had significantly higher levels of Ang-2 compared with non-active disease (P = 0·02). Serum levels of both Ang-2 and Tie-2 were not correlated with laboratory markers such as ESR, CRP, white blood cell count, platelet count and albumin. Conclusions, Serum Ang-2 and Tie-2 levels are elevated in patients with IBD. These markers may mediate angiogenesis and vascular permeability in the mucosa of patients with IBD. [source] Vascular endothelium: the battlefield of dengue virusesFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2008Atanu Basu Abstract Increased vascular permeability without morphological damage to the capillary endothelium is the cardinal feature of dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS). Extensive plasma leakage in various tissue spaces and serous cavities of the body, including the pleural, pericardial and peritoneal cavities in patients with DHF, may result in profound shock. Among various mechanisms that have been considered include immune complex disease, T-cell-mediated, antibodies cross-reacting with vascular endothelium, enhancing antibodies, complement and its products, various soluble mediators including cytokines, selection of virulent strains and virus virulence, but the most favoured are enhancing antibodies and memory T cells in a secondary infection resulting in cytokine tsunami. Whatever the mechanism, it ultimately targets vascular endothelium (making it a battlefield) leading to severe dengue disease. Extensive recent work has been done in vitro on endothelial cell monolayer models to understand the pathophysiology of vascular endothelium during dengue virus (DV) infection that may be translated to help understand the pathogenesis of DHF/DSS. The present review provides a broad overview of the effects of DV infection and the associated host responses contributing towards alterations in vascular endothelial cell physiology and damage that may be responsible for the DHF/DSS. [source] Severe alterations of endothelial and glial cells in the blood-brain barrier of dystrophic mdx miceGLIA, Issue 3 2003Beatrice Nico Abstract In this study, we investigated the involvement of the blood-brain barrier (BBB) in the brain of the dystrophin-deficient mdx mouse, an experimental model of Duchenne muscular dystrophy (DMD). To this purpose, we used two tight junction markers, the Zonula occludens (ZO-1) and claudin-1 proteins, and a glial marker, the aquaporin-4 (AQP4) protein, whose expression is correlated with BBB differentiation and integrity. Results showed that most of the brain microvessels in mdx mice were lined by altered endothelial cells that showed open tight junctions and were surrounded by swollen glial processes. Moreover, 18% of the perivascular glial endfeet contained electron-dense cellular debris and were enveloped by degenerating microvessels. Western blot showed a 60% reduction in the ZO-1 protein content in mdx mice and a similar reduction in AQP4 content compared with the control brain. ZO-1 immunocytochemistry and claudin-1 immunofluorescence in mdx mice revealed a diffuse staining of microvessels as compared with the control ones, which displayed a banded staining pattern. ZO-1 immunogold electron microscopy showed unlabeled tight junctions and the presence of gold particles scattered in the endothelial cytoplasm in the mdx mice, whereas ZO-1 gold particles were exclusively located at the endothelial tight junctions in the controls. Dual immunofluorescence staining of ,-actin and ZO-1 revealed colocalization of these proteins. As in ZO-1 staining, the pattern of immunolabeling with anti,,-actin antibody was diffuse in the mdx vessels and pointed or banded in the controls. ,-actin immunogold electron microscopy showed gold particles in the cytoplasms of endothelial cells and pericytes in the mdx mice, whereas ,-actin gold particles were revealed on the endothelial tight junctions and the cytoskeletal microfilaments of pericytes in the controls. Perivascular glial processes of the mdx mice appeared faintly stained by anti-AQP4 antibody, while in the controls a strong AQP4 labeling of glial processes was detected at light and electron microscope level. The vascular permeability of the mdx brain microvessels was investigated by means of the horseradish peroxidase (HRP). After HRP injection, extensive perivascular areas of marker escape were observed in mdx mice, whereas HRP was exclusively intravascularly localized in the controls. Inflammatory cells, CD4-, CD8-, CD20-, and CD68-positive cells, were not revealed in the perivascular stroma of the mdx brain. These findings indicate that dystrophin deficiency in the mdx brain leads to severe injury of the endothelial and glial cells with disturbance in ,-actin cytoskeleton, ZO-1, claudin-1, and AQP4 assembly, as well as BBB breakdown. The BBB alterations suggest that changes in vascular permeability are involved in the pathogenesis of the neurological dysfunction associated with DMD. GLIA 42:235,251, 2003. © 2003 Wiley-Liss, Inc. [source] Co-production of vascular endothelial cadherin and inducible nitric oxide synthase by endothelial cells in periapical granulomaINTERNATIONAL ENDODONTIC JOURNAL, Issue 3 2006S. Hama Abstract Aim, To clarify the mechanisms of inflammatory cell migration in human periapical granulomas by examining vascular endothelial (VE) cadherin and inducible nitric oxide synthase (iNOS)-producing cells. Methodology, Periapical tissues were obtained from patients during endodontic surgery and were divided into two portions. After fixing the tissues with acetone or 4% paraformaldehyde in phosphate-buffered saline, 5- ,m-thick paraffin or cryostat sections were prepared, respectively. The paraffin sections of the inflamed tissues were evaluated histologically with haematoxylin,eosin stains. Cryostat sections of the tissue, diagnosed as periapical granulomas, were then examined by either immunohistochemistry using anti-human VE-cadherin or iNOS antibodies (Abs) for the characterization of infiltrating cells. In addition, co-localization of VE-cadherin and iNOS production was also analysed by two-colour immunofluorescence image analysis. Results, Endothelial cells were strongly stained with iNOS Abs. Macrophages, lymphocytes, polymorphonuclear leucocytes and fibroblasts also exhibited iNOS production. These iNOS-positive cells accumulated around the blood vessels. On the other hand, VE-cadherin production was exhibited in only endothelial cells. Two-colour immunofluorescence image analysis using VE-cadherin and iNOS Abs demonstrated that iNOS-producing endothelial cells also showed VE-cadherin production. Conclusions, Vascular endothelial-cadherin produced by endothelial cells could be regulated by iNOS-producing cells in periapical granulomas and might play a pivotal role in vascular permeability. [source] Disparity between prostate tumor interior versus peripheral vasculature in response to verteporfin-mediated vascular-targeting therapyINTERNATIONAL JOURNAL OF CANCER, Issue 3 2008Bin Chen Abstract Photodynamic therapy (PDT) is a light-based cancer treatment modality. Here we employed both in vivo and ex vivo fluorescence imaging to visualize vascular response and tumor cell survival after verteporfin-mediated PDT designed to target tumor vasculature. EGFP-MatLyLu prostate tumor cells, transduced with EGFP using lentivirus vectors, were implanted in athymic nude mice. Immediately after PDT with different doses of verteporfin, tumor-bearing animals were injected with a fluorochrome-labeled albumin. The extravasation of fluorescent albumin along with tumor EGFP fluorescence was monitored noninvasively with a whole-body fluorescence imaging system. Ex vivo fluorescence microscopy was performed on frozen sections of tumor tissues taken at different times after treatment. Both in vivo and ex vivo imaging demonstrated that vascular-targeting PDT with verteporfin significantly increased the extravasation of fluorochrome-labeled albumin in the tumor tissue, especially in the tumor periphery. Although PDT induced substantial vascular shutdown in interior blood vessels, some peripheral tumor vessels were able to maintain perfusion function up to 24 hr after treatment. As a result, viable tumor cells were typically detected in the tumor periphery in spite of extensive tumor cell death. Our results demonstrate that vascular-targeting PDT with verteporfin causes a dose- and time-dependent increase in vascular permeability and decrease in blood perfusion. However, compared to the interior blood vessels, peripheral tumor blood vessels were found less sensitive to PDT-induced vascular shutdown, which was associated with subsequent tumor recurrence in the tumor periphery. © 2008 Wiley-Liss, Inc. [source] Modulation of angiogenesis is effective in a model of rheumatoid arthritisJOURNAL OF ANATOMY, Issue 5 2002A. O. Afuwape A feature of rheumatoid arthritis (RA) is prominent hyperplasia of the synovium, which results in an increased distance between the invasive pannus and the existing synovial vasculature. Concomitantly the hyperplastic tissue imposes an augmented metabolic demand on the pre-existing vasculature. As a consequence the synovium in RA becomes hypoxic, resulting in an increased rate of formation of new blood vessels, to supply nutrients and oxygen. Targeting the vasculature in RA is a potential therapeutic approach in RA. VEGF, a key vascular permeability and angiogenic factor, is expressed in RA. In this study we utilised adenovirus expressing the secreted form of the extracellular domain of the Flt-1 VEGF receptor (sFlt-1) to inhibit VEGF in the collagen-induced arthritis (CIA) model, to determine whether blocking the effects of vegf might be an effective treatment for RA. AdvsFlt-1, administered intravenously on the first day of arthritis, significantly suppressed CIA. For example, on d 6 of arthritis the mean increase in paw thickness, which reflects oedema, for untreated and null adenovirus-treated animals was 0.23 ± 0.05 mm and 0.38 ± 0.08, respectively, compared to 0.07 ± 0.05 for AdvsFlt-1-treated mice (P < 0.001 vs. Adv0-treated and untreated mice by 2-way anova). Western blot analyses revealed the presence of a 100-kDa band, corresponding to human sFlt-1, in liver extracts from arthritic mice infected with AdvsFlt-1 at 24 h but not 72 h after infection. This band was absent in liver extracts from Adv0-infected mice and all synovial extracts. Measurement of protein levels by ELISA demonstrated the presence of sFlt-1 in liver, synovium and serum, although levels declined by 72 h post infection. These data suggest efficient but transient expression of sFlt-1. Sera from adenovirus infected mice were found to contain antiviral antibodies and additionally, sera from AdvsFlt-1-infected but not Adv0-infected mice recognised human recombinant sFlt-1. These observations demonstrate that adenoviral mediated delivery of human sFlt-1 leads to transient gene expression and suppression of CIA. This effect is reduced later in the course of disease due to the expression of antiadenovirus as well as antisFlt-1 antibodies. Future studies will assess the effect of combination treatment, using AdvsFlt-1 together with anti-TNF(antibody, to prolong the beneficial effects of VEGF blockade. These results suggest that blocking the pro-angiogenic and permeability action of VEGF may be beneficial for treatment of RA. [source] VEGF in biological controlJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2007Ellen C. Breen Abstract Vascular endothelial growth factor A (VEGF-A) belongs to a family of heparin binding growth factors that include VEGF-B, VEGF-C, VEGF-D, and placental-like growth factor (PLGF). First discovered for its ability to regulate vascular endothelial cell permeability, VEGF is a well-known angiogenic factor that is important for vascular development and maintenance in all mammalian organs. The development of molecular tools and pharmacological agents to selectively inhibit VEGF function and block angiogenesis and/or vascular permeability has led to great promise in the treatment of various cancers, macular degeneration, and wound healing. However, VEGF is also important in animals for the regulation of angiogenesis, stem cell and monocyte/macrophage recruitment, maintenance of kidney and lung barrier functions and neuroprotection. In addition to its role in regulating endothelial cell proliferation, migration, and cell survival, VEGF receptors are also located on many non-endothelial cells and act through autrocrine pathways to regulate cell survival and function. The following review will discuss the role of VEGF in physiological angiogenesis as well as its role in non-angiogenic processes that take place in adult organs. J. Cell. Biochem. 102: 1358,1367, 2007. © 2007 Wiley-Liss, Inc. [source] How to overcome (and exploit) tumor hypoxia for targeted gene therapyJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2003Olga Greco Tumor hypoxia has long been recognized as a critical issue in oncology. Resistance of hypoxic areas has been shown to affect treatment outcome after radiation, chemotherapy, and surgery in a number of tumor sites. Two main strategies to overcome tumor hypoxia are to increase the delivery of oxygen (or oxygen-mimetic drugs), and exploiting this unique environmental condition of solid tumors for targeted therapy. The first strategy includes hyperbaric oxygen breathing, the administration of carbogen and nicotinamide, and the delivery of chemical radiosensitizers. In contrast, bioreductive drugs and hypoxia-targeted suicide gene therapy aim at activating cytotoxic agents at the tumor site, while sparing normal tissue from damage. The cellular machinery responds to hypoxia by activating the expression of genes involved in angiogenesis, anaerobic metabolism, vascular permeability, and inflammation. In most cases, transcription is initiated by the binding of the transcription factor hypoxia-inducible factor (HIF) to hypoxia responsive elements (HREs). Hypoxia-targeting for gene therapy has been achieved by utilizing promoters containing HREs, to induce selective and efficient transgene activation at the tumor site. Hypoxia-targeted delivery and prodrug activation may add additional levels of selectivity to the treatment. In this article, the latest developments of cancer gene therapy of the hypoxic environment are discussed, with particular attention to combined protocols with ionizing radiation. Ultimately, it is proposed that by adopting specific transgene activation and molecular amplification systems, resistant hypoxic tumor tissues may be effectively targeted with gene therapy. J. Cell. Physiol. 197: 312,325, 2003© 2003 Wiley-Liss, Inc. [source] Capillary permeability and extracellular volume fraction in uterine cervical cancer as patient outcome predictors: Measurements by using dynamic MRI spin-lattice relaxometryJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2008Véronique Dedieu PhD Abstract Purpose To improve the outcome prediction of uterine cervical carcinoma by measuring the vascular permeability (kep) and the extracellular volume fraction (ve) of the tumor from Dynamic T1 - IRM Relaxometry. Materials and Methods Twenty-six patients with proven cervical carcinoma were divided into good outcome and poor outcome groups. Classic tumor prognostic factors, the longest diameter L and the volume V of the tumor, were measured from morphologic MR images. The tumor parameters kep and ve were determined from the relaxometry time-curve acquired during the contrast uptake after a bolus intravenous injection of an extracellular contrast agent. Results All "small" tumors (L<35 mm or V<11 cm3) were good outcome with 100% sensitivity but a rather low specificity (36% and 43% for L and V, respectively). With regard to the physiopathological parameter kep, "large" tumors (L , 35mm) can also be classified as good outcome on the condition that kep , 2.2 min,1 with 100% sensitivity and 89% specificity. Regarding the extracellular volume fraction (ve), no significant difference was observed between the two groups. Conclusion Measurement of the tumor vascular permeability might be useful to predict prognostic, to evaluate the treatment efficacy, and to adapt a proper therapy schedule. J. Magn. Reson. Imaging 2008;27:846,853. © 2008 Wiley-Liss, Inc. [source] Dynamic contrast-enhanced magnetic resonance imaging as a surrogate marker of tumor response to anti-angiogenic therapy in a xenograft model of glioblastoma multiformeJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 3 2002Axel Gossmann MD Abstract Purpose To evaluate the effects of a neutralizing anti-vascular endothelial growth factor (anti-VEGF) antibody on tumor microvascular permeability, a proposed indicator of angiogenesis, and tumor growth in a rodent malignant glioma model. Materials and Methods A dynamic contrast-enhanced magnetic resonance imaging (MRI) technique, permitting noninvasive in vivo and in situ assessment of potential therapeutic effects, was used to measure tumor microvascular characteristics and volumes. U-87, a cell line derived from a human glioblastoma multiforme, was implanted orthotopically into brains of athymic homozygous nude rats. Results Treatment with the monoclonal antibody A4.6.1, specific for VEGF, significantly inhibited tumor microvascular permeability (6.1 ± 3.6 mL min,1100 cc,1), compared to the control, saline-treated tumors (28.6 ± 8.6 mL min,1100 cc,1), and significantly suppressed tumor growth (P < .05). Conclusion Findings demonstrate that tumor vascular permeability and tumor growth can be inhibited by neutralization of endogenous VEGF and suggest that angiogenesis with the maintenance of endothelial hyperpermeability requires the presence of VEGF within the tissue microenvironment. Changes in tumor vessel permeability and tumor volumes as measured by contrast-enhanced MRI provide an assay that could prove useful for clinical monitoring of anti-angiogenic therapies in brain tumors. J. Magn. Reson. Imaging 2002;15:233,240. © 2002 Wiley-Liss, Inc. [source] Femur window,a new approach to microcirculation of living bone in situJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2005N. Hansen-Algenstaedt Abstract Background: The processes of osteogenesis, bone remodelling, fracture repair and metastasis to bone are determined by complex sequential interactions involving cellular and microcirculatory parameters. Consequently studies targeting the analysis of microcirculatory parameters on such processes should mostly respect these complex conditions. However these conditions could not yet be achieved in vitro and therefore techniques that allow a long-term observation of functional and structural parameters of microcirculation in bone in vivo at a high spatial resolution are needed to monitor dynamic events, such as fracture healing, bone remodelling and tumor metastasis. Methods: We developed a bone chamber implant (femur window) for long-term intravital microscopy of pre-existing bone and its microcirculation at an orthotopic site in mice preserving the mechanical properties of bone. After bone chamber implantation vascular density, vessel diameter, vessel perfusion, vascular permeability and leukocyte-endothelial interactions (LEIs) in femoral bone tissue of c57-black mice (n = 11) were measured quantitatively over 12 days using intravital fluorescence microscopy. Furthermore a model for bone defect healing and bone metastasis in the femur window was tested. Results: Microvascular permeability and LEIs showed initially high values after chamber implantation followed by a significant decrease to a steady state at day 6 and 12, whereas structural parameters remained unaltered. Bone defect healing and tumor growth was observed over 12 and 90 days respectively. Conclusion: The new femur window design allows a long-term analysis of structural and functional properties of bone and its microcirculation quantitatively at a high spatial resolution. Altered functional parameters of microcirculation after surgical procedures and their time dependent return to a steady state underline the necessity of long-term observations to achieve unaltered microcirculatory parameters. Dissection of the complex interactions between bone and microcirculation enables us to evaluate physiological and pathological processes of bone and may give new insights especially in dynamic events e.g. fracture healing, bone remodeling and tumor metastasis. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Vascular endothelial growth factor 121 and 165 in the subacromial bursa are involved in shoulder joint contracture in type II diabetics with rotator cuff diseaseJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2003Akiyoshi Handa Vascular endothelial growth factor (VEGF) is a glycoprotein that plays an important role in neovascularization and increases vascular permeability. We reported that VEGF is involved in motion pain of patients with rotator cuff disease by causing synovial proliferation in the subacromial bursa (SAB). The present study investigates whether VEGF is also involved in the development of shoulder contracture in diabetics with rotator cuff disease. We examined 67 patients with rotator cuff disease, including 36 with complete cuff tears, 20 with incomplete tears, and 11 without apparent tears (subacromial bursitis). The patients were into groups according to the presence or absence of diabetes (14 type II diabetics and 53 non-diabetics). Specimens of the synovium of the SAB were obtained from all patients during surgery. Expression of the VEGF gene in the synovium of the subacromial bursa was evaluated by using the reverse transcriptase polymerase chain reaction. The VEGF protein was localized by immunohistochemistry, and the number of vessels was evaluated based on CD34 immunoreactivity. The results showed that VEGF mRNA was expressed in significantly more diabetics (100%, 14/14) than in non-diabetics (70%, 37/53) (P = 0.0159, Fisher's test). Investigation of VEGF isoform expression revealed VEGF121 in all 14 diabetics and in 37 of the 53 non-diabetics, VEGF 165 in 12 of the 14 diabetics and in 21 of the 53 non-diabetics, and VEGF 189 in 1 of the 14 diabetics and in 2 of the 53 non-diabetics. No VEGF206 was expressed in either group. VEGF protein was localized in both vascular endothelial cells and synovial lining cells. The mean number of VEGF-positive vessels and the vessel area were also significantly greater in the diabetics (p < 0.015, Mann-Whitney U test). Synovial proliferation and shoulder joint contracture were more common in the diabetics (P = 0.0329 and P = 0.073, respectively; Fisher's test). The mean preoperative range of shoulder motion significantly differed in terms of elevation between two groups: 103.8° in diabetics and 124.9° in no diabetics (p = 0.0039 Mann,Whitney U test). In contrast, external rotation did not significantly differ: 44° in diabetics and 49° in non-diabetics (p ° 0.4957, Mann,Whitney U test). These results suggest that VEGF121 and VEGF165 expression in the SAB is responsible for the development of shoulder joint contracture, especially in elevation, among type II diabetic patients with rotator cuff disease. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Enhanced expression of vascular endothelial growth factor by periodontal pathogens in gingival fibroblastsJOURNAL OF PERIODONTAL RESEARCH, Issue 1 2003Kanyarat Suthin Vascular endothelial growth factor (VEGF) has recently attracted attention as a potent inducer of vascular permeability and angiogenesis. Aberrant angiogenesis is often associated with lesion formation in chronic periodontitis. The aim of the present study was to investigate the properties of VEGF expression in human gingival fibroblasts (HGF) culture. HGF were stimulated with lipopolysaccharide (LPS), vesicle (Ve) and outer membrane protein (OMP) from Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. HGF constitutively produced VEGF and levels were significantly enhanced (P < 0.01) by stimulation with Ve and OMP from A. actinomycetemcomitans and P. gingivalis at concentrations of 10 µg/ml or higher. On the other hand, VEGF levels were not increased by LPS stimulation. VEGF mRNA expression was also observed in Ve- and OMP-stimulated HGF. A vascular permeability enhancement (VPE) assay was performed using guinea pigs to ascertain whether supernatant from cultures of Ve- and OMP-stimulated HGF enhance vascular permeability in vivo. Supernatant from cultures of Ve- and OMP-stimulated HGF strongly induced VPE. This was markedly suppressed upon simultaneous injection of anti-VEGF polyclonal antibodies with the supernatant. Heating and protease treatment of the stimulants reduced the VEGF enhancing levels in Ve and OMP in vitro. These results suggest that Ve and OMP may be crucial heat-labile and protease-sensitive components of periodontal pathogens that enhance VEGF expression. In addition, VEGF might be associated with the etiology of periodontitis in its early stages according to neovascularization stimulated by periodontal pathogens causing swelling and edema. [source] Anti-angiogenic, antinociceptive and anti-inflammatory activities of Lonicera japonica extractJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2008Hye-Jung Yoo This study aimed to elucidate some novel pharmacological activities of Lonicera japonica (Caprifoliaceae), which is widely used in Oriental folk medicine. The ethanolic extract of L. japonica (LJ) dose dependently inhibited chick chorioallantoic membrane angiogenesis. The antinociceptive activity of LJ was assessed using the acetic acid-induced constriction model in mice. LJ showed anti-inflammatory activity in two in-vivo models: the vascular permeability and air pouch models. LJ suppressed the production of nitric oxide via down-regulation of inducible nitric oxide synthase in lipopolysaccharide-stimulated RAW264.7 macrophage cells. However, LJ was unable to suppress induction of cyclooxygenase-2 in the stimulated macrophage cells. LJ decreased the reactive oxygen species level in the stimulated macrophage cells. In brief, the flowers of L. japonica possess potent anti-angiogenic and antinociceptive activities, in addition to anti-inflammatory activity, which partly supports its therapeutic efficacy. [source] Anti-allergic properties of Mangifera indica L. extract (Vimang) and contribution of its glucosylxanthone mangiferinJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2006Dagmar García Rivera Vimang is the brand name of formulations containing an extract of Mangifera indica L., ethnopharmacologically used in Cuba for the treatment of some immunopathological disorders, including bronchial asthma, atopic dermatitis and other allergic diseases. However, the effects of Vimang on allergic response have not been reported until now. In this study, the effects of Vimang and mangiferin, a C-glucosylxanthone isolated from the extract, on different parameters of allergic response are reported. Vimang and mangiferin showed a significant dose-dependent inhibition of IgE production in mice and anaphylaxis reaction in rats, histamine-induced vascular permeability and the histamine release induced by compound 48/80 from rat mast cells, and of lymphocyte proliferative response as evidence of the reduction of the amount of B and T lymphocytes able to contribute to allergic response. In these experiments, ketotifen, promethazine and disodium cromoglicate were used as reference drugs. Furthermore, we demonstrated that Vimang had an effect on an in-vivo model of inflammatory allergy mediated by mast cells. These results constitute the first report of the anti-allergic properties of Vimang on allergic models, as well as suggesting that this natural extract could be successfully used in the treatment of allergic disorders. Mangiferin, the major compound of Vimang, contributes to the anti-allergic effects of the extract. [source] Molecular control of blood flow and angiogenesis: role of nitric oxideJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2009W. C. SESSA Summary., In the past decade, the importance of the vascular endothelium as a multifunctional regulator of vascular smooth muscle physiology and pathophysiology has been appreciated. Indeed, the endothelium responds to hemodynamic stimuli (pressure, shear stress and wall strain) and locally manufactured mediators (such as bradykinin, prostaglandins, angiotensin II and nitric oxide) that can influence blood flow, cell trafficking into tissue and angiogenesis. In this chapter, the importance of nitric oxide (NO) as a mediator of blood flow control, vascular permeability and angiogenesis will be discussed. [source] Plasma levels and skin-eosinophil-expression of vascular endothelial growth factor in patients with chronic urticariaALLERGY, Issue 11 2009A. Tedeschi Background:, Although chronic urticaria (CU) is often regarded as autoimmune in nature, only less than 50% of sera from CU patients contain histamine-releasing autoantibodies. This suggests that other factors may contribute to its pathogenesis. We evaluated the possible involvement of vascular endothelial growth factor (VEGF), one of the major mediators of vascular permeability, in CU. Methods:, Eighty consecutive adult patients with CU and 53 healthy subjects were studied. VEGF and prothrombin fragment F1+2 were measured by enzyme immunoassays. Autologous plasma skin test (APST) was performed in CU patients and, in six of them, skin biopsy specimens were taken from wheals to evaluate the immunohistochemical expression of VEGF and eosinophil cationic protein (ECP). Results:, Plasma VEGF concentrations were higher in CU patients (8.00 ± 0.90 pmol/l) than in controls (0.54 ± 0.08 pmol/l) (P = 0.0001) and tended to parallel both the severity of CU and to correlate with F1+2 levels. APST was positive in 85.1% of patients. VEGF concentration was significantly higher in APST-positive than in APST-negative patients (P = 0.0003). Immunohistochemically, all specimens from patients with CU showed a strong expression of VEGF (P = 0.002) that colocalized with ECP, a classic eosinophil marker. Conclusions:, VEGF plasma levels are elevated in CU and parallel the disease severity. This supports a possible role of this molecule in CU pathophysiology. Eosinophils are the main cellular source of VEGF in CU lesional skin. [source] Effects of aging and HIF-1, deficiency on permeability of hippocampal vesselsMICROSCOPY RESEARCH AND TECHNIQUE, Issue 1 2006Masaki Ueno Abstract We examined age-related changes in the blood,brain barrier (BBB) of neural cell-specific hypoxia inducible factor-1, (HIF-1,) deficient mice, which showed hydrocephalus with neuronal cell loss, to investigate an effect of neural cell-specific HIF-1, deficiency or hydrocephalus on vascular function. Vascular permeability of horseradish peroxidase (HRP) and binding of cationized ferritin (CF) particles to the endothelial cell luminal surface, as a marker of glycocalyx, were investigated. The thickness of CF-labeled glycocalyx was significantly decreased in the cortex in mutant mice compared with that of control mice, although it was not paralleled by increased vascular permeability. In addition, strong staining for HRP was seen around vessels located along the hippocampal fissure in 24-month-old mutant mice. The reaction product of HRP appeared in an increasing number of the endothelial cell abluminal vesicles and within the thickened basal lamina of arterioles in the hippocampus, showing increased vascular permeability. There were no leaky vessels in 10-week-old mutant mice or 10-week-old and 24-month-old control mice. These findings suggest the necessity of two factors, aging and hydrocephalus, for BBB dysfunction in HIF-1, deficient mice. Microsc. Res. Tech. 69:29,35, 2006. © 2006 Wiley-Liss, Inc. [source] Fluid challenge in patients at risk for fluid loading-induced pulmonary edemaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2004M. Matejovic Background:, This study evaluated the effects of protocol-guided fluid loading on extravascular lung water (EVLW) and hemodynamics in a group of patients at high risk for volume expansion-induced pulmonary and systemic edema. Methods:, Nine acutely admitted septic patients with acute lung injury (ALI) were prospectively studied. In addition to sepsis and ALI, the following criteria indicating increased risk for edema formation had to be fulfilled: increased vascular permeability defined as microalbuminuria greater than fivefold normal and hypoalbuminemia <30 g l,1. Two hundred-ml boluses of a 10% hydroxyethyl starch (HES) was titrated to obtain best filling pressure/stroke volume relation. Extravascular lung water and intrathoracic blood volume (ITBV) were measured using a transpulmonary double-indicator dilution technique. Baseline data were compared with data at the end of fluid loading and 3 h postchallenge. Results:, At study entry the mean EVLW was 13 ml kg,1, and the mean EVLW/ITBV ratio (indicator of pulmonary permeability) was 0.72 (normal range 0.20,0.30). To attain optimal preload/stroke volume relation 633 ± 240 ml of HES was needed. Fluid loading significantly increased preload (CVP, PAOP and ITBV), and stroke volume. Effective pulmonary capillary pressure (Pcap) rose only slightly. As a result, the Pcap,PAOP gradient decreased. Despite increased cardiac output, EVLW did not change by plasma expansion. Conclusion:, In this selected group of at-risk patients, the optimization of cardiac output guided by the concept of best individual filling pressure/stroke volume relationship did not worsen permeability pulmonary edema. [source] Fluorescein leakage of the optic disc: time course in primary open-angle glaucomaOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 3 2010Niklas Plange Abstract Purpose:, To identify and quantify the time course of fluorescein leakage of the optic nerve head in primary open-angle glaucoma (POAG) and controls. Methods:, Twenty patients with POAG (aged 58 ± 10 years) and 14 controls (aged 51 ± 12 years, p = 0.07) were included in a prospective study. Fluorescein leakage of the optic disc was quantified using digital image analysis. A new leakage ratio (fluorescence of the optic disc divided by fluorescence of the surrounding retina) was defined and fluorescein leakage was quantified at 7,8, 9,10, 11,12, and 13,14 min after injection of 2.5 cc sodium fluorescein (10%). Results:, The fluorescein leakage exhibited a significantly different time course with higher leakage ratio values in POAG compared to controls (7,8 min: 1.24 ± 0.32 vs 1.16 ± 0.12; 9,10 min: 1.37 ± 0.37 vs 1.19 ± 0.1; 11,12 min: 1.38 ± 0.36 vs 1.24 ± 0.13; 13,14 min: 1.44 ± 0.36 vs 1.27 ± 0.13; p = 0.004). The change in optic disc fluorescence from 7,8 min to 9,10 min was significantly higher in POAG compared to controls (0.13 ± 0.09 vs 0.03 ± 0.07; p = 0.002). Conclusion:, The time course of fluorescein leakage is significantly different in POAG compared to controls. This might reflect damage of the optic disc vasculature related to increased vascular permeability. [source] Pathogenesis of diabetic retinopathy and the renin-angiotensin systemOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 6 2003Hideharu Funatsu Abstract Despite the beneficial effects of good glycaemic control, loss of vision because of diabetic retinopathy (DR) still occurs. Recent studies have suggested that hypertension is a risk factor for the development and progression of DR and that blood pressure reduction can delay the progression of retinopathy. The renin-angiotensin system is activated by chronic hyperglycaemia, and the vitreous fluid level of angiotensin II (AII) is elevated in patients with proliferative diabetic retinopathy and diabetic macular oedema. AII increases vascular permeability and promotes neovascularization. It has been suggested that an autocrine-paracrine relationship may exist between AII and vascular endothelial growth factor in the ocular tissues. Accordingly, angiotensin-converting enzyme inhibitors or AII Type 1 (AT1) receptor blockers may be useful therapeutic agents for preventing the progression of DR. [source] Antinociceptive, antiin,ammatory and acute toxicity effects of Salvia leriifolia Benth. seed extract in mice and ratsPHYTOTHERAPY RESEARCH, Issue 4 2003Hossein Hosseinzadeh Abstract The antinociceptive and antiin,ammatory effects as well as the acute toxicity of Salvia leriifolia aqueous seed extract were studied in mice and rats. Antinociceptive activity was assessed using the hot-plate and tail ,ick tests. The effect on acute in,ammation was studied using vascular permeability increased by acetic acid and xylene-induced ear oedema in mice. The activity against chronic in,ammation was assessed using the cotton pellet test in rats. The LD50 of the extract was found to be 19.5 g/kg (i.p.) in mice. The aqueous seed extract showed signi,cant and dose-dependent (1.25,10 g/kg) antinociceptive activity over 7 h, and was inhibited by naloxone pretreatment. Signi,cant and dose-dependent (2.5,10 g/kg) activity was observed against acute in,ammation induced by acetic acid and in the xylene ear oedema test. In the chronic in,ammation test the extract (2.5,5 g/kg) showed signi,cant and dose-dependent antiin,ammatory activity. The aqueous seed extract of S. leriifolia may therefore have supraspinal antinociceptive effects which may be mediated by opioid receptors, and showed considerable effects against acute and chronic in,ammation. Copyright © 2003 John Wiley & Sons, Ltd. [source] Effect of methanol extract from flower petals of Tagetes patula L. on acute and chronic inflammation modelPHYTOTHERAPY RESEARCH, Issue 3 2002Yoshimasa Kasahara Abstract The methanol extract of the florets of Tagetes patula (MEFTP) inhibited acute and chronic inflammation in mice and rats. MEFTP significantly suppressed hind-paw oedema induced by ,-carrageenin in mice. Furthermore, MEFTP not only inhibited the hind-paw oedema induced by various acute phlogogens, such as histamine, serotonin, bradykinin and prostaglandin E1, but also suppressed the increase of vascular permeability by acetic acid, indicating that it primarily acts at the exudative stage of inflammation. In the chronic inflammation, MEFTP did not inhibit the proliferation of granulation tissue when tested by the cotton pellet method, however, it was effective on the development of adjuvant arthritis in rats. Oral MEFTP inhibited acute and chronic inflammation in mice and rats. Copyright © 2002 John Wiley & Sons, Ltd. [source] The Role of Platelet-activating Factor in the Mammalian Female Reproductive TractREPRODUCTION IN DOMESTIC ANIMALS, Issue 6 2008U Tiemann Contents Platelet-activating factor (PAF) is a potent lipid mediator produced by various cell types of mammals and is involved in an inflammatory-like process with increased vascular permeability. Platelet-activating factor exerts its actions through the activation of specific PAF receptors (PAF-R) found in cells and tissues of the female reproductive tract. The aim of this article was summarized briefly in the current research on the role of PAF in female reproductive functions. Platelet-activating factor has been implicated in processes of ovulation, implantation and parturition because of its angiogenic and growth factor properties. This factor is influenced by ovarian steroid hormones in bringing about changes in the uterus and is a candidate molecule for initial embryo,maternal dialogue. Tissue concentrations of PAF are regulated by the equilibrium between biosynthesis and degradation by PAF-acetylhydrolase (PAF-AH). Antagonists of PAF interfere with ovulation and implantation. Platelet-activating factor, its receptor, and PAF-AH activity play an important role in the maintenance of pregnancy. [source] Role of Protease Activated Receptor 2 in Experimental Acute Lung Injury and Lung FibrosisTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 4 2009Xiao Su Abstract Protease activated receptor 2 (PAR2) is widely-distributed (lung, liver, kidney, etc.) and expressed by variety of cells (i.e. leukocytes, epithelial cells, endothelial cells, and fibroblast). PAR2 may participate in many pathological processes, such as, inflammation, injury, as well as fibrosis. Therefore, in this study, we tested whether PAR2 would exert a role in acid-induced acute lung injury, E. coli pneumonia, bleomycin-induced acute lung injury and fibrosis. Acid, E. coli, or bleomycin were intratracheally instilled into the lungs of both wildtype and PAR2 knockout mice to detect differences in pulmonary edema, lung vascular permeability, lung fibrosis, and other parameters. Knockout of PAR2 did not affect the extent of pulmonary edema and lung vascular permeability in acid-induced acute lung injury. Also, both activation of PAR2 in the airspaces of the lung and deletion of PAR2 did not alter the magnitude of pulmonary edema and lung vascular permeability in E. coli pneumonia. Finally, PAR2 deficiency did not affect the severity of lung inflammation and lung fibrosis in bleomycin-induced acute lung injury and lung fibrosis models. Thus, PAR2 does not appear to play a critical role in the pathogeneses of experimental acid-induced acute lung injury, E. coli pneumonia, and bleomycin-induced acute lung injury and pulmonary fibrosis in mice. Anat Rec, 2009. © 2009 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||