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Increased Permeability (increased + permeability)
Selected AbstractsIncreased permeability of asthmatic epithelial cells to pollutants.CLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2002Does this mean that they are intrinsically abnormal? No abstract is available for this article. [source] Protein kinase C and the development of diabetic vascular complicationsDIABETIC MEDICINE, Issue 12 2001K. J. Way Abstract Hyperglycemic control in diabetes is key to preventing the development and progression of vascular complications such as retinopathy, nephropathy and neuropathy. Increased activation of the diacylglycerol (DAG)-protein kinase C (PKC) signal transduction pathway has been identified in vascular tissues from diabetic animals, and in vascular cells exposed to elevated glucose. Vascular abnormalities associated with glucose-induced PKC activation leading to increased synthesis of DAG include altered vascular blood flow, extracellular matrix deposition, basement membrane thickening, increased permeability and neovascularization. Preferential activation of the PKC, isoform by elevated glucose is reported to occur in a variety of vascular tissues. This has lead to the development of LY333531, a PKC, isoform specific inhibitor, which has shown potential in animal models to be an orally effective and nontoxic therapy able to produce significant improvements in diabetic retinopathy, nephropathy, neuropathy and cardiac dysfunction. Additionally, the antioxidant vitamin E has been identified as an inhibitor of the DAG-PKC pathway, and shows promise in reducing vascular complications in animal models of diabetes. Given the overwhelming evidence indicating a role for PKC activation in contributing to the development of diabetic vascular complications, pharmacological therapies that can modulate this pathway, particularly with PKC isoform selectivity, show great promise for treatment of vascular complications, even in the presence of hyperglycemia. Diabet. Med. 18, 945,959 (2001) [source] Brain barrier dysfunction in Cuban Epidemic Optic NeuropathyEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2008A. González-Quevedo Monteagudo Background and purpose:, There are practically no references to cerebrospinal fluid(CSF) studies in tropical or nutritional neuropathies. In the present paper we present the results of CSF studies in patients with Cuban Epidemic Optic Neuropathy (CEON) during epidemic and endemic periods, with an appraisal as to the contribution of brain barriers, function in the pathophysiology of this disease. Methods:, Two hundred and five patients with CEON were studied during the epidemic period (1992,1993) and 12 patients outside the outbreak (1995,1997). CSF protein determination and electrophoresis were carried out, as well as serum and CSF albumin and immunoglobulin G (IgG) quantitation for calculating IgG and Qalb indexes, in order to evaluate intrathecal IgG synthesis and the permeability of the blood,CSF barrier (B-CSF B). Results:, One fourth of the patients had increased permeability of the B-CSF B, but damage was more frequent between 16 and 60 days from onset of disease, disappearing after 120 days. B-CSF B dysfunction was more prevalent in patients with severe neurological impairment, although it was not related to the severity of ophthalmological damage. The group of patients studied outside of the outbreak (endemic period) showed similar results. Discussion:, The possible association of increased permeability of the B-CSF B with oxidative stress, which lies on the basis of this epidemic outbreak, is discussed. [source] Changes in oxidative balance in rat pericytes exposed to diabetic conditionsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2004A. Manea Abstract Recent data indicate that the oxidative stress plays an important role in the pathogenesis of diabetes and its complications such as retinopathy, nephropathy and accelerated atherosclerosis. In diabetic retinopathy, it was demonstrated a selective loss of pericytes accompanied by capillary basement membrane thickening, increased permeability and neovascularization. This study was designed to investigate the role of diabetic conditions such as high glucose, AGE-Lysine, and angiotensin II in the modulation of antioxidant enzymes activities, glutathione level and reactive oxygen species (ROS) production in pericytes. The activity of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total glutathione (GSH) was measured spectrophotometrically. The production of ROS was detected by spectrofluorimetry and fluorescence microscopy after loading the cells with 2,-7, dichlorofluoresceine diacetate; as positive control H2O2 was used. Intracellular calcium was determined using Fura 2 AM assay. The results showed that the cells cultured in high glucose alone, do not exhibit major changes in the antioxidant enzyme activities. The presence of AGE-Lys or Ang II induced the increase of SOD activity. Their combination decreased significantly GPx activity and GSH level. Athree times increase in ROS production and a significant impairment of intracellular calcium homeostasis was detected in cells cultured in the presence of the three pro-diabetic agents used. In conclusion, our data indicate that diabetic conditions induce in pericytes: (i) an increase of ROS and SOD activity, (ii) a decrease in GPx activity and GSH level, (iii) a major perturbation of the intracellular calcium homeostasis. The data may explain the structural and functional abnormalities of pericytes characteristic for diabetic retinopathy. [source] High-performance separation of small inorganic anions on a methacrylate-based polymer monolith grafted with [2(methacryloyloxy)ethyl] trimethylammonium chlorideJOURNAL OF SEPARATION SCIENCE, JSS, Issue 15-16 2009Damian Connolly Abstract A glycidyl methacrylate- co -ethylene dimethacrylate monolith in capillary format (100 ,m/id) has been grafted with chains of poly([2(methacryloyloxy)ethyl] trimethylammonium chloride (poly-META) and applied to the ion-chromatographic separation of selected inorganic anions. Grafting chains of META onto the generic monolithic scaffold resulted in a monolith with ,electrolyte responsive flow permeability', which manifested as increased permeability in the presence of electrolyte solutions. Using an eluent of 2 mM sodium benzoate and on-column contactless conductivity detection, a test mixture of six common anions was isocratically separated and detected within 12 min, with the first four anions baseline resolved within a retention time window of 3.2 min. Retention time precision was ,1.2% for all anions tested. Separation efficiencies of 15 000 N/m were achieved for fluoride at 1 ,L/min, with column efficiencies up to 29 500 N/m obtained at a lower flow rate of 100 nL/min. Furthermore, repeatability of the column modification procedure using photografting methods was acceptable, with retention times between replicate columns matching within 9%. [source] Microcirculatory Dysfunction in Chronic Venous Insufficiency (CVI)MICROCIRCULATION, Issue S1 2000MICHAEL JÜNGER ABSTRACT The elevated ambulatory pressure in the peripheral venous system of chronic venous insufficiency (CVI) patients manifests itself not only in the form of disturbed macrocirculation but also and particularly in microangiopathic changes. For this reason, it is closely correlated with trophic disorders of the skin and can ultimately lead to ulceration. Using microcirculation research techniques, we are able to provide clear evidence of a typical microangiopathy in chronic venous insufficiency. Fifty CVI patients in Widmer stages I, II, and III were examined with fluorescence video microscopy, intravital video capillaroscopy, transcutaneous oxygen partial pressure measurement, TcpO2 and laser Doppler flowmetry. The effects of compression therapy with individually fitted compression stockings on capillary morphology were studied over a period of 4 weeks in 20 CVI patients in Widmer stages I and II. The capillary pressure was measured during simulated muscle contraction using a servo-null micropressure system. We periodically drew blood from the dorsalis pedis vein and a brachial vein of 11 healthy test persons and 8 patients with stage III CVI during experimental venous hypertension in order to evaluate the expression pattern of leukocyte adhesion molecules involved in inflammation: LFA-1 (CD11a), Mac-1 (CD11b), p150,95 (CD11c), CD18, VLA-4 (CD49d), and L-selectin (CD62L). In the same patients, we used immunohistochemical methods to examine clinically unaffected skin and the skin near an ulcer, focusing on the adhesion molecules ICAM-1, VCAM-1, and E-selectin. The microangiopathic changes observed with worsening clinical symptoms include a decrease in the number of capillaries, glomerulus-like changes in capillary morphology, a drop in the oxygen content (tcpO2) of the skin, increased permeability of the capillaries to low-molecular-weight substances, increased laser Doppler flux reflecting elevated subcutaneous flow, and diminished vascular reserve. These microangiopathic changes worsen in linear proportion to the clinical severity of chronic venous insufficiency. In patients with venous ulcerations, the baseline expression of LFA-1 and VLA-4 on lymphocytes, Mac-1 expression on the myeloid cell line, and L-selectin expression on all three cell lines was not significantly different from that in healthy controls. During orthostatic stress, there was a significant reduction in the expression of L-selectin in blood cells collected at foot level in the controls (p = 0.002), but not in the patients. Clinical improvement by compression therapy was accompanied by an increase in the number of nutritive capillaries, while the diameter of the capillaries and the dermal papillae was reduced. When ulcers healed in a short period (<6 weeks), we observed a concomitant increase in the number of capillaries (p < 0.05). Microangiopathy appears before trophic disorders of the skin develop. Even trophically normal skin areas may have dilated nutritive capillaries, an early sign of disturbed skin perfusion. These changes represent a plausible explanation for the development and to recurrency tendency of venous ulcers. The reduced expression of lymphocytic L-selectin in healthy controls during the orthostatic stress test may be an indication that the cells are activated by venous stasis. Clinically effective therapeutic measures improve the impaired microcirculation of the skin in the ankle area. [source] Soluble cellular adhesion molecules, selectins, VEGF and endothelin-1 in patients with Wuchereria bancrofti infection and association with clinical statusPARASITE IMMUNOLOGY, Issue 1-2 2005P. Esterre SUMMARY Lymphatic filariasis, a mosquito-transmitted disease commonly known as Bancroftian filariasis, is characterized by debilitating pathology linked to the progression of lymphoedema to a chronic state of elephantiasis. We performed longitudinal measurements of endothelial adhesion and angiogenic molecules in 63 Polynesian patients living in an hyperendemic focus of Wuchereria bancrofti. Decreased serum concentrations of soluble (s-) L selectin (CD62L) were noticed in sera of of patients with chronic conditions (hydrocele and elephantiasis). Chyluria was associated with increased vascular endothelial growth factor (VEGF) levels, whereas elephantiasis presented a high endothelin-1 (ET-1) profile. By contrast, increased serum concentrations of soluble intercellular (sICAM-1, CD54), but not of vascular cell (sVCAM-1, CD106), adhesion molecules were observed in sera of patients with bacterial lymphangitis used as controls. These trends are consistent with the increased permeability of vascular structures, a major clinical feature observed in acute lymphatic pathology (of bacterial or filarial origin), and of fundamental differences in the pathogenesis of hydrocele and elephantiasis. Using markers correlated with the clinical status (high ET-1 and VEGF levels for elephantiasis and chyluria, respectively; low CD62L levels for hydrocoele and elephantiasis) it should be possible to monitor disease progression in lymphatic filariasis. [source] Skin Barrier, Hydration, and pH of the Skin of Infants Under 2 Years of AgePEDIATRIC DERMATOLOGY, Issue 2 2001Francesca Giusti M.D. A total of 70 infants, 45 girls and 25 boys, ages 8,24 months, and 30 healthy women were studied by means of transepidermal water loss (TEWL), capacitance, and pH measurements at two different skin sites, the volar forearm and the buttocks. No significant differences in TEWL were found between infants and adults, either on the buttocks or on the volar forearm. On the contrary, capacitance values were higher in infants. Their skin also appeared less acid than that of adults, with high statistical significance. No TEWL, capacitance, or pH variations were observed in infants according to sex and age. On the basis of the above data, the skin of infants 8,24 months of age shows functional signs of immaturity. This may lead to an increased permeability and a reduced capacity for defense against chemical and microbial aggression. [source] Expression of Vascular Endothelial Growth Factor Receptors in Bovine Cystic FolliclesREPRODUCTION IN DOMESTIC ANIMALS, Issue 3 2008N Isobe Contents Cystic follicles have excess fluid derived from blood flow in the theca interna of the follicle; therefore, the vasculature network is related to cystic follicle formation. Vascular endothelial growth factor (VEGF) is a potent stimulator of blood vessel permeability and angiogenesis. The aim of this study was to examine the expression of VEGF receptors proteins and mRNA in cystic follicles to elucidate the VEGF system in cystic follicles. The expression of protein for VEGF receptors; fms-like-tyrosine kinase-1 (Flt-1) and foetal liver kinase-1 (Flk-1) was detected by the immunohistochemical method. The mRNA expression of Flt-1 and Flk-1 in cystic follicles was determined by RT-PCR. Concentration of oestradiol-17, and progesterone in the follicular fluid of cystic follicles was determined using ELISA. Flt-1- and Flk-1 proteins were localized in granulosa and theca interna cells and endothelial cells of theca layers. The intensity of Flt-1 and Flk-1 immunoreaction was similar among cystic follicles with various ratios of oestradiol-17,/progesterone concentrations. The expression of Flt-1 and Flk-1 mRNA was similar, regardless of the ratio of oestradiol-17, to progesterone in follicular fluid. These results demonstrate that cystic follicles have both VEGF receptors in the granulosa and theca interna layers, which may be responsible for the increased permeability of microvessels, causing the accumulation of follicular fluid in cystic follicles. [source] RNAi-mediated reversible opening of the blood-brain barrierTHE JOURNAL OF GENE MEDICINE, Issue 8 2008Matthew Campbell Abstract Background The blood-brain barrier (BBB) contains tight junctions (TJs) which reduce the space between adjacent endothelial cells lining the fine capillaries of the microvasculature of the brain to form a selective and regulatable barrier. Methods Using a hydrodynamic approach, we delivered siRNA targeting the TJ protein claudin-5 to the endothelial cells of the BBB in mice. Results We have shown a significant decrease in claudin-5 mRNA levels 24 and 48 hours post-delivery of siRNA, with levels of protein expression decreasing up to 48 hours post-injection compared to uninjected, phosphate-buffered saline (PBS)-injected and non-targeting siRNA-injected mice. We observed increased permeability at the BBB to molecules up to 742 Da, but not 4400 Da, using tracer molecule perfusion and MRI analysis. To illustrate the functional efficacy of size-selective and transient barrier opening, we have shown that enhanced delivery of the small neuropeptide thyrotropin-releasing hormone (TRH) (MW 360 Da) to the brains of mice 48 hours post-injection of siRNA targeting claudin-5 significantly modifies behavioural output. Conclusions These data demonstrate that it is now possible to transiently and size-selectively open the BBB in mice, allowing in principle the delivery of a wide range of agents for the establishment and treatment of experimental mouse models of neurodegenerative, neuropsychiatric and malignant diseases. Copyright © 2008 John Wiley & Sons, Ltd. [source] Formation of plant cuticle: evidence for the occurrence of the peroxygenase pathwayTHE PLANT JOURNAL, Issue 2 2003José Lequeu Summary Cuticle plays a major role as a protective barrier in plants. Despite its physiological importance, the mode of formation of this complex structure remains poorly understood. In particular, none of the putative enzymes involved in the biosynthesis of the cutin, the matrix of cuticle, have been cloned. We have shown previously that peroxygenase is able to catalyze in vitro the epoxidation step required for the biosynthesis of C18 cutin monomers. In the present work, we have confirmed in planta that this oxidase is indeed a key enzyme involved in the formation of cutin. Thus, in maize leaves, the specific inactivation of peroxygenase by organophosphorothioates resulted in a dramatic decrease of cuticular epoxide content, as visualized by a specific histochemical technique that was accompanied by a reduced thickness of the cuticle. A strict correlation could also be established between the extent of inhibition of the peroxygenase and the modification of the cuticle triggered by a family of structurally related inhibitors. Importantly, these effects were restricted to plants that contain a cutin originating from C18 monomers. The altered cuticle of maize, treated with the peroxygenase inhibitor, was characterized by an increased permeability to pesticides. In addition, such plants became largely susceptible to infection by fungi, implying that the cuticle represents a crucial target for the modulation of the response in plant,pathogen interactions. [source] 2433: A revolutionary hypothesis to explain Marx's line and progressive disease at the lid marginACTA OPHTHALMOLOGICA, Issue 2010AJ BRON Purpose The conjunctiva of the lid margin is protected from direct exposure to the atmosphere, by the tear meniscus. We examine the pathophysiological consequences of evaporation from this compartment. Methods A consideration of empirical data. Results The concave meniscus thins progressively to the point where it is pinned at the mucocutaneous junction (MCJ). We predict that, as a result, over the interblink period, evaporation generates a solute gradient which peaks behind the MCJ and is amplified over multiple cycles of the blink. We hypothesise that this creates a hyperosmolar state here which: i. stresses epithelial cells behind the MCJ, ii. stimulates a high cell turnover and iii. leads to immaturity of the surface cells and their glycocalyx. This is considered to explain an increased permeability to dyes at this site (rose bengal, lissamine green and fluorescein) and the stainability with dyes which is termed Marx's line. This gradient mechanism could also concentrate proteins, such as inflammatory mediators, at this location. Conclusion Since Marx's line lies directly behind the terminal Meibomian ducts and acini, chronic stress in this region is further invoked to explain forward migration of Marx's line and the MCJ which occurs with age and the induction of primary Meibomian gland dysfunction. Arguments are put forward to explain how this mechanism might be accentuated in dry eye and how the globe might be protected from this gradient effect in the region of the ,black line', where the tear film is segregated from the meniscus after the blink. Factors pro and con the hypothesis are discussed. [source] The action of pro-inflammatory cytokines on retinal endothelial cell barrier permeability: protective effect of corticosteroidsACTA OPHTHALMOLOGICA, Issue 2008AF AMBROSIO Purpose The pro-inflammatory cytokines interleukin-1, (IL-1,) and tumor necrosis factor-alpha (TNF-,) were found to be increased in the vitreous of diabetic patients and in diabetic rat retinas, and increased cytokine levels were correlated with elevated retinal vascular permeability. In this work, we investigated the mechanisms underlying IL-1,- and TNF-,-induced retinal endothelial cell permeability and evaluated the ability of a glucocorticoid, dexamethasone (DEX), to prevent changes in permeability. Methods Primary cultures of bovine retinal endothelial cells (BRECs) were grown on transwell filters and exposed to IL-1, and TNF-,. BRECs permeability to 70 kDa RITC-dextran was measured. The content and localization of tight junction proteins was assessed by Western blotting and immunocytochemistry. Results IL-1, and TNF-, increased retinal endothelial cell permeability in a concentration- and time-dependent manner, but TNF-, was more effective (increased permeability at a lower dose and shorter time-point). The increase in permeability was not due to changes in cell viability. IL-1, and TNF-, altered ZO-1 and claudin-5 content. TNF-, also decreased ZO-1 staining at the cell border. Pre-treatment with DEX prevented TNF-,-induced cell permeability, and the protective effect of DEX was partially abolished by the glucocorticoid receptor antagonist RU486. Conclusion These data demonstrate that TNF-, and IL-1, potently induce endothelial cell permeability through alterations in tight junctions. Also, the study supports the potential therapeutic use of glucocorticoids to reduce retinal vascular permeability. Support: FCT (Portugal), NIH, JDRF and Allergan [source] Abrogation of IFN-, mediated epithelial barrier disruption by serine protease inhibitionCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2005L. E. M. Willemsen Summary The intestinal barrier function is often impaired in a variety of diseases including chronic inflammatory bowel disease. Increased intestinal permeability during episodes of active disease correlates with destruction or rearrangement of the tight junction protein complex. IFN-, has been widely studied for its effect on barrier function and tight junction structures but its mode of action remains unclear. Since the claudin family of tight junction proteins is proposed to be involved in barrier maintenance we studied the effect of IFN-, on claudin expression in relation to epithelial barrier function. Cycloheximide and protease inhibitors were used to study mechanisms of IFN-, mediated barrier disruption. Intestinal epithelial cells were exposed to IFN-, and permeability was evaluated by horse radish peroxidase (HRP) and 4 kD FITC-dextran fluxes. Occludin and claudin-1, -2, -3, and -4 tight junction protein expression was determined by Western blotting. Occludin and claudin-2 protein expression was dramatically reduced after IFN-, exposure, which correlated with increased permeability for HRP and FITC-dextran. Interestingly, cleavage of claudin-2 was observed after incubation with IFN-,. Serine protease inhibitor AEBSF completely abrogated IFN-, mediated barrier disruption which was associated with preservation of claudin-2 expression. Moreover, IFN-, induced loss of barrier integrity was found to affect claudin-2 and occludin expression through different mechanisms. Since inhibition of serine protease activity abrogates IFN-, mediated barrier disruption this may be an important target for therapeutic intervention. [source] HIGH GLUCOSE-INDUCED HUMAN UMBILICAL VEIN ENDOTHELIAL CELL HYPERPERMEABILITY IS DEPENDENT ON PROTEIN KINASE C ACTIVATION AND INDEPENDENT OF THE Ca2+,NITRIC OXIDE SIGNALLING PATHWAYCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2005Lei Dang SUMMARY 1.,Endothelial barrier dysfunction plays a pivotal role in the pathogenesis of diabetic vascular complications. The precise molecular mechanisms by which hyperglycaemia causes the increased permeability in endothelial cells are not yet well understood. In the present study, we investigated whether high concentrations of glucose induce endothelial permeability through the activation of protein kinase C (PKC) and/or the calcium,nitric oxide (NO) signalling pathway in human umbilical vein endothelial cells (HUVEC). 2.,Endothelial permeability was measured by albumin diffusion across endothelial monolayers under the stimuli of high glucose (HG; 20 mmol/L), 100 nmol/L phorbol-myristate-acetate (PMA) or 100 nmol/L histamine. The intracellular calcium concentration ([Ca2+]i) was detected in HUVEC using the fluorescent probe fura-2 AM. The effects of PKC inhibitors (LY379196 and hypocrellin A) and the NO synthase (NOS) inhibitor NG -monomethyl- l -arginine (l -NMMA) on endothelial permeability and [Ca2+]i were determined. 3.,High glucose and PMA increased endothelial permeability associated with decreased [Ca2+]i, whereas histamine triggered significant increases in endothelial permeability, accompanied by increases in [Ca2+]i in HUVEC. Hypocrellin A (HA) and LY379196 reversed both HG- and histamine-induced endothelial permeability. The NOS inhibitor l -NMMA only abolished histamine- and not HG-induced endothelial permeability. Neither LY379196, HA nor l -NMMA had any significant effects on alterations in [Ca2+]i caused by HG and histamine. 4.,These results indicate that increased endothelial permeability in HUVEC induced by HG is dependent on PKC activity and is independent of the [Ca2+]i,NO pathway. Increased endothelial permeability due to other inflammatory factors, such as histamine, may also be mediated by the PKC pathway. Thus, PKC inhibitors would be a potential therapeutic approach to endothelial dysfunction induced by hyperglycaemia, as well as other inflammatory factors, in diabetes. [source] | |||||||||||||