Barrier Dysfunction (barrier + dysfunction)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Barrier Dysfunction

  • brain barrier dysfunction

  • Selected Abstracts

    Brain barrier dysfunction in Cuban Epidemic Optic Neuropathy

    A. 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]

    Transepidermal water loss reflects permeability barrier status: validation in human and rodent in vivo and ex vivo models

    Joachim W. Fluhr
    Abstract:, Permeability barrier function is measured with instruments that assess transepidermal water loss (TEWL), either with closed- or open-loop systems. Yet, the validity of TEWL as a measure of barrier status has been questioned recently. Hence, we tested the validity of this measure by comparing TEWL across a wide range of perturbations, with a variety of methods, and in a variety of models. TEWL rates with two closed-chamber systems (VapoMeter and H4300) and one closed-loop system (MEECO) under different experimental in vivo conditions were compared with data from four open-loop instruments, i.e. TM 210, TM 300, DermaLab and EP 1. The instruments were compared in vivo both in humans and hairless mice skin subjected to different degrees of acute barrier disruption. The values obtained with bioengineering systems were correlated with absolute water loss rates, determined gravimetrically. Measurements with both closed and open systems correlated not only with each other, but each method detected different degrees of barrier dysfunction. Although all instruments differentiated among gradations in TEWL in the mid-range of barrier disruption in vivo, differences in very low and very high levels of disruption were less accurately measured with the H4300 and DermaLab systems. Nevertheless, a high Pearson correlation coefficient (r) was calculated for data from all instruments vs. gravimetrically assessed TEWL. Together, these results verify the utility of TEWL as a measure of permeability barrier status. Moreover, all tested instruments are reliable tools for the assessment of variations in permeability barrier function. [source]

    Effect of inhibition of prostaglandin E2 production on pancreatic infection in experimental acute pancreatitis

    HPB, Issue 5 2007
    Abstract Objective. Acute pancreatitis is one the important causes of systemic inflammatory response syndrome (SIRS). SIRS results in gut barrier dysfunction that allows bacterial translocation and pancreatic infection to occur. Indomethacin has been used to reduce inflammatory process and bacterial translocation in experimental models. The purpose of this study was to determine the effect of inhibition of prostaglandin E2 (PGE2) production on pancreatic infection. Materials and methods. An experimental model of severe acute pancreatitis (AP) was utilized. The animals were divided into three groups: sham (surgical procedure without AP induction); pancreatitis (AP induction); and indomethacin (AP induction plus administration of 3 mg/kg of indomethacin). Serum levels of interleukin (IL)-6 and IL-10, PGE2, and tumor necrosis factor (TNF)-, were measured 2 h after the induction of AP. We analyzed the occurrence of pancreatic infection with bacterial cultures performed 24 h after the induction of AP. The occurrence of pancreatic infection (considered positive when the CFU/g was >105), pancreatic histologic analysis, and mortality rate were studied. Results. In spite of the reduction of IL-6, IL-10, and PGE2 levels in the indomethacin group, TNF-, level, bacterial translocation, and pancreatic infection were not influenced by administration of indomethacin. The inhibition of PGE2 production did not reduce pancreatic infection, histologic score, or mortality rate. Conclusion. The inhibition of PGE2 production was not able to reduce the occurrence of pancreatic infection and does not have any beneficial effect in this experimental model. Further investigations will be necessary to discover a specific inhibitor that would make it possible to develop an anti-inflammatory therapy. [source]

    Activator protein-1 signalling pathway and apoptosis are modulated by poly(ADP-ribose) polymerase-1 in experimental colitis

    IMMUNOLOGY, Issue 4 2004
    Basilia Zingarelli
    Summary Poly(ADP-ribose) polymerase-1 (PARP-1) is activated in response to DNA injury in the nucleus of eukaryotic cells and has been implicated in intestinal barrier dysfunction during inflammatory bowel diseases. In this study we investigated whether PARP-1 may regulate the inflammatory response of experimental colitis at the level of signal transduction mechanisms. Mice genetically deficient of PARP-1 (PARP-1,/,) and wild-type littermates were subjected to rectal instillation of trinitrobenzene sulphonic acid (TNBS). Signs of inflammation were monitored for 14 days. In wild-type mice, TNBS treatment resulted in colonic ulceration and marked apoptosis, which was associated with decreased colon content of the antiapoptotic protein Bcl-2, whereas the proapoptotic Bax was unchanged. Elevated levels of plasma nitrate/nitrite, metabolites of nitric oxide (NO), were also found. These inflammatory events were associated with activation of c-Jun-NH2 terminal kinase (JNK), phosphorylation of c-Jun and activation of the nuclear transcription factor activator protein-1 (AP-1) in the colon. In contrast, PARP-1,/, mice exhibited a significant reduction of colon damage and apoptosis, which was associated with increased colonic expression of Bcl-2 and lower levels of plasma nitrate/nitrite when compared to wild-type mice. Amelioration of colon damage was associated with a significant reduction of the activation of JNK and reduction of the DNA binding of AP-1. The data indicate that PARP-1 exerts a pathological role in colitis possibly by regulating the early stress-related transcriptional response through a positive modulation of the AP-1 and JNK pathways. [source]

    The intestinal barrier and its regulation by neuroimmune factors

    ĺ. v. Keita
    Abstract Background, The ability to control uptake across the mucosa and protect from damage of harmful substances from the lumen is defined as intestinal barrier function. A disturbed barrier dysfunction has been described in many human diseases and animal models, for example, inflammatory bowel disease, irritable bowel syndrome, and intestinal hypersensitivity. In most diseases and models, alterations are seen both of the paracellular pathway, via the tight junctions, and of the transcellular routes, via different types of endocytosis. Recent studies of pathogenic mechanisms have demonstrated the important role of neuroimmune interaction with the epithelial cells in the regulation of barrier function. Neural impulses from extrinsic vagal and/or sympathetic efferent fibers or intrinsic enteric nerves influence mucosal barrier function via direct effects on epithelial cells or via interaction with immune cells. For example, by nerve-mediated activation by corticotropin-releasing hormone or cholinergic pathways, mucosal mast cells release a range of mediators with effects on transcellular, and/or paracellular permeability (for example, tryptase, TNF-,, nerve growth factor, and interleukins). Purpose, In this review, we discuss current physiological and pathophysiological aspects of the intestinal barrier and, in particular, its regulation by neuroimmune factors. [source]

    Review: Role of developmental inflammation and blood,brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases

    H. B. Stolp
    The causes of most neurological disorders are not fully understood. Inflammation and blood,brain barrier dysfunction appear to play major roles in the pathology of these diseases. Inflammatory insults that occur during brain development may have widespread effects later in life for a spectrum of neurological disorders. In this review, a new hypothesis suggesting a mechanistic link between inflammation and blood,brain barrier function (integrity), which is universally important in both neurodevelopmental and neurodegerative diseases, is proposed. The role of inflammation and the blood,brain barrier will be discussed in cerebral palsy, schizophrenia, Parkinson's disease, Alzheimer's disease and multiple sclerosis, conditions where both inflammation and blood,brain barrier dysfunction occur either during initiation and/or progression of the disease. We suggest that breakdown of normal blood,brain barrier function resulting in a short-lasting influx of blood-born molecules, in particular plasma proteins, may cause local damage, such as reduction of brain white matter observed in some newborn babies, but may also be the mechanism behind some neurodegenerative diseases related to underlying brain damage and long-term changes in barrier properties. [source]

    Are there predominant strains and toxins of Staphylococcus aureus in atopic dermatitis patients?

    Genotypic characterization, adult patients with atopic dermatitis, toxin determination of S. aureus isolated in adolescent
    ABSTRACT The colonization of Staphylococcus aureus is one of the most important aggravating factors of atopic dermatitis (AD). Until now, the importance of S. aureus in AD and a positive correlation between colonization with S. aureus and clinical severity/skin barrier function has been demonstrated. The aim of this study was to determine whether there are certain clones of S. aureus which colonize the skin of AD patients. For this purpose, the genotype of S. aureus isolated from AD patients was examined by newly-developed typing methods. With 36 strains of S. aureus isolated from 35 patients with AD, spa typing, multi-locus sequence typing (MLST), and staphylococcal toxin gene assay by multiplex polymerase chain reaction, were performed. Clinical severity and skin barrier function were evaluated with eczema area and severity index (EASI) and with transepidermal water loss (TEWL). Among 36 strains of S. aureus, 14 sequence types (ST) and 20 spa types were identified, suggesting a very heterogeneous genetic composition of S. aureus and the absence of a prevailing genotype in S. aureus colonized with AD patients. Furthermore, there was no specific genotype of S. aureus which was associated with the clinical severity of AD or skin barrier dysfunction. A toxin gene assay, however, showed the predominance of S. aureus strains carrying sea and/or tsst-1. To the best of our knowledge, this is the first report to show the genetic composition of S. aureus strains isolated from AD patients determined by sequence-based typing methods. [source]

    Simulated reflux decreases vocal fold epithelial barrier resistance,,

    THE LARYNGOSCOPE, Issue 8 2010
    CF-SLP, Elizabeth Erickson MS
    Abstract Objectives/Hypothesis: The vocal fold epithelium provides a barrier to the entry of inhaled and systemic challenges. However, the location of the epithelium makes it vulnerable to damage. Past research suggests, but does not directly demonstrate, that exposure to gastric reflux adversely affects the function of the epithelial barrier. Understanding the nature of reflux-induced epithelial barrier dysfunction is necessary to better recognize the mechanisms for vocal fold susceptibility to this disease. Therefore, we examined the effects of physiologically relevant reflux challenges on vocal fold transepithelial resistance and gross epithelial and subepithelial appearance. Study Design: Ex vivo, mixed design with between-group and repeated-measures analyses. Methods: Healthy, native porcine vocal folds (N = 52) were exposed to physiologically relevant acidic pepsin, acid-only, or pepsin-only challenges and examined with electrophysiology and light microscopy. For all challenges, vocal folds exposed to a neutral pH served as control. Results: Acidic pepsin and acid-only challenges, but not pepsin-only or control challenges significantly reduced transepithelial resistance within 30 minutes. Reductions in transepithelial resistance were irreversible. Challenge exposure produced minimal gross changes in vocal fold epithelial or subepithelial appearance as evidenced by light microscopy. Conclusions: These findings demonstrate that acidic environments characteristic of gastric reflux compromise epithelial barrier function without gross structural changes. In healthy, native vocal folds, reductions in transepithelial resistance could reflect reflux-related epithelial disruption. These results might guide the development of pharmacologic and therapeutic recommendations for patients with reflux, such as continued acid-suppression therapy and patient antireflux behavioral education. Laryngoscope, 2010 [source]

    Lacunar stroke is associated with diffuse blood,brain barrier dysfunction,

    ANNALS OF NEUROLOGY, Issue 2 2009
    FMedSci, Joanna M. Wardlaw MD
    Objective Lacunar stroke is common (25% of ischemic strokes) and mostly because of an intrinsic cerebral microvascular disease of unknown cause. Although considered primarily to be an ischemic process, the vessel and tissue damage could also be explained by dysfunctional endothelium or blood,brain barrier (BBB) leak, not just ischemia. We tested for subtle generalized BBB leakiness in patients with lacunar stroke and control patients with cortical ischemic stroke. Methods We recruited patients with lacunar and mild cortical stroke. We assessed BBB leak in gray matter, white matter, and cerebrospinal fluid, at least 1 month after stroke, using magnetic resonance imaging before and after intravenous gadolinium. We measured tissue enhancement for 30 minutes after intravenous gadolinium by two image analysis approaches (regions of interest and tissue segmentation). We compared the enhancement (leak) between lacunar and cortical patients, and associations with key variables, using general linear modeling. Results We recruited 51 lacunar and 46 cortical stroke patients. Signal enhancement after gadolinium was higher in lacunar than cortical stroke patients in white matter (p < 0.001) and cerebrospinal fluid (p < 0.003) by both analysis methods, independent of other variables. Signal enhancement after gadolinium was also associated with increasing age and enlarged perivascular spaces, but these did not explain the lacunar-cortical difference. Interpretation Patients with lacunar stroke have subtle, diffuse BBB dysfunction in white matter. Further studies are required to determine the relative contributions of BBB dysfunction and/or ischemia to the microvascular and brain abnormalities in lacunar stroke. Ann Neurol 2009;65:194,202 [source]

    Filaggrin null mutations associate with increased frequencies of allergen-specific CD4+ T-helper 2 cells in patients with atopic eczema

    T. McPherson
    Summary Background, Filaggrin null mutations associate with atopic eczema and also with asthma when present with eczema. However, while epidermal dysfunction is an important factor in disease pathogenesis, it is unclear how such dysfunction interacts with immune responses to contribute to cutaneous and other inflammatory atopic disease. Objectives, To gain a better understanding of the mechanisms underlying such predisposition in order to understand different disease phenotypes and possibly identify potential treatment targets. Methods, We studied 33 individuals with atopic eczema and used interleukin-4 immunospot and human leucocyte antigen class II tetrameric complexes to investigate the peripheral blood allergen-specific CD4+ T-cell responses. Results, Filaggrin null mutations associated with significantly (P < 0·05) higher frequencies of allergen-specific CD4+ T-helper 2 cell responses. Conclusions, These data would support a model where barrier dysfunction possibly promotes greater allergen penetration and delivery to drive allergen-specific CD4+ T cells. This could further contribute to respiratory and cutaneous inflammatory disease. [source]

    Role of mast cells in the development of pancreatitis-induced multiple organ dysfunction

    M. Dib
    Background: Activated mast cells can produce and release a number of inflammatory mediators involved in the pathophysiology of acute conditions. The aim of the present study was to evaluate the role of activated tissue mast cells in the pathogenesis of multiple organ dysfunction syndrome following acute pancreatitis (AP). Methods: AP was induced by the intraductal infusion of 5 per cent sodium taurodeoxycholate in the rat. Some 30 min before induction of AP, a mast cell stabilizer (sodium cromoglycate (SCG)) or antihistamines (pyrilamine, cyproheptadine, meclizine and amitriptyline) were administered intra peritoneally. Plasma exudation of radiolabelled albumin, histamine, myeloperoxidase (MPO), monocyte chemoattractant protein (MCP) 1 and adhesion molecules (platelet endothelial cell adhesion molecule (PECAM) 1 and L-selectin) were measured. Results: The mast cell stabilizer significantly reduced plasma exudation in the pancreas, colon and lungs (P < 0·05), decreased the release of histamine at 1 h (P < 0·05), and reduced MPO activity and MCP-1 levels in the colon and lungs (P < 0·05) but not in the pancreas. Expression of PECAM-1 and L-selectin on total circulating leucocytes in rats with AP and SCG pretreatment did not differ from that in sham controls, while levels in animals that had AP and saline pretreatment were half of those seen following sham operation. Conclusion: Activation of mast cells after induction of AP is involved in the development of endothelial barrier dysfunction in both the pancreas and extrapancreatic organs/tissues, particularly in the lungs and colon. This may, at least partly, contribute to the sequential development of multiple organ dysfunction and organ/tissue-specific endothelial barrier dysfunction. © 2002 British Journal of Surgery Society Ltd [source]

    New insights into the pathogenic role of advanced glycation in diabetic retinopathy

    Purpose Retinopathy is the most common microvascular complication of diabetes. The clinicopathology of microvascular lesions and neuroglial dysfunction in the diabetic retina have been extensively studied, although the relative contribution of various biochemical sequelae of hyperglycaemia remains ill-defined. The formation and accumulation of advanced glycation endproducts (AGEs) is an important pathogenic pathway in the progression of diabetic retinopathy although some of the cellular and molecular pathologies initiated by these adducts in retinal cells remain unknown. Methods This presentation will cover several aspects of AGE-linked retinal pathology and demonstrate opportunities for therapeutic intervention. The studies outlined will cover a wide range of molecular cell biology approaches using appropriate in vitro and in vivo model systems. Results It will be demonstrated that AGEs form in vivo in the diabetic retina through the reaction of alpha-oxaloaldehydes leading to significant modifications of retinal proteins. Evidence will be presented to demonstrate that these AGEs act as significant effectors of retinal vascular and neuroglial cell dysfunction, leading to pro-inflammatory responses, growth factor imbalance and, ultimately, neurovascular lesions such as blood retinal barrier dysfunction and microvascular degeneration. The protective role of novel AGE-inhibitors will also be shown. Conclusion Evidence now points towards a pathogenic role for advanced glycation in the initiation and progression of diabetic retinopathy and this review lecture will outline the current state of knowledge of AGE-related pathology in the retina at a cellular and molecular level. [source]


    Lei 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]