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Sample records for experimental peridural fibrosis

  1. Prevention of peridural fibrosis using a cyclooxygenase-2 inhibitor (nonsteroidal anti-inflammatory drug) soaked in absorbable gelatin sponge: an experimental comparative animal model.

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    Sae-Jung, Surachai; Jirarattanaphochai, Kitti

    2013-07-15

    Experimental study. To evaluate the efficacy and safety of peridural parecoxib-soaked absorbable gelatin sponge, and cellulose membrane on peridural fibrosis prevention in an animal model. Postoperative peridural fibrosis is one of the causes of failed back surgery syndrome. Nonsteroidal anti-inflammatory drugs inhibit the inflammatory response, while an absorbable gelatin sponge or cellulose membrane interposes between the dura and the paraspinal muscle to staunch the surgical bleeding. These mechanisms may prevent peridural fibrosis. Forty L5-L6 laminectomized adult Sprague-Dawley rats were randomly allocated into 4 groups. The high parecoxib group received 6 mg of parecoxib soaked into an absorbable gelatin sponge placed over the dura. The low parecoxib group was given 2 mg of parecoxib soaked into an absorbable gelatin sponge. The dura in the cellulose group was covered with a cellulose membrane, while the control group received normal saline drip before surgical wound closure. All rats were killed at 6 weeks for histopathological assessment. The fibroblast density, inflammatory cell density, fibrous adherence, and adverse events were quantified. The obtained results were analyzed statistically. The respective mean fibroblast density in the high parecoxib, low parecoxib, cellulose, and control groups was 217.77 ± 51.76, 317.51 ± 126.92, 321.80 ± 90.94, and 328.48 ± 73.41 cells/mm², while the respective mean inflammatory cell density was 539.65 ± 236.52, 910.17 ± 242.59, 1011.84 ± 239.30, and 1261.78 ± 319.68 cells/mm². The mean fibroblast and inflammatory cell densities of the high parecoxib group were significantly lower than the control. The high parecoxib group also showed statistically less fibrous adherence than low parecoxib, cellulose, and control groups. The high-dose parecoxib-soaked absorbable gelatin sponge can prevent peridural fibrosis without complications. The low-dose parecoxib and cellulose membrane provided no significant benefit vis

  2. Tumor necrosis factor-α blockade in recurrent and disabling chronic sciatica associated with post-operative peridural lumbar fibrosis: results of a double-blind, placebo randomized controlled study.

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    Nguyen, Christelle; Palazzo, Clémence; Grabar, Sophie; Feydy, Antoine; Sanchez, Katherine; Zee, Nathalie; Quinquis, Laurent; Ben Boutieb, Myriam; Revel, Michel; Lefèvre-Colau, Marie-Martine; Poiraudeau, Serge; Rannou, François

    2015-11-19

    The aim of this study was to assess the efficacy and safety of tumor necrosis factor (TNF)-α inhibition with infliximab (IFX) in treating recurrent and disabling chronic sciatica pain associated with post-operative peridural lumbar fibrosis. A double-blind, placebo-controlled study randomized 35 patients presenting with sciatica pain associated with post-operative peridural lumbar fibrosis to two groups: IFX (n = 18), a single intravenous injection of 3 mg/kg IFX; and placebo (n = 17), a single saline serum injection. The primary outcome was a 50 % reduction in sciatica pain on a visual analog scale (VAS) at day 10. Secondary outcomes were radicular and lumbar VAS pain at day 0 and radicular and lumbar VAS pain, Québec disability score, drug-sparing effect and tolerance at days 10, 30, 90, and 180. At day 10, the placebo and IFX groups did not differ in the primary outcome (50 % reduction in sciatica pain observed in three (17.6 %) versus five (27.8 %) patients; p = 0.69). The number of patients reaching the patient acceptable symptom state for radicular pain was significantly higher in the placebo than IFX group after injection (12 (70.6 %) versus five (27.8 %) patients; p = 0.01). The two groups were comparable for all other secondary outcomes. Treatment with a single 3 mg/kg IFX injection for post-operative peridural lumbar fibrosis-associated sciatica pain does not significantly reduce radicular symptoms at day 10 after injection. ClinicalTrials.gov NCT00385086 ; registered 4 October 2006 (last updated 15 October 2015).

  3. Comparison of a caprolactone/lactide film (mesofol) to two polylactide film products as a barrier to postoperative peridural adhesion in an ovine dorsal laminectomy model.

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    Klopp, Lisa S; Simon, Bruce J; Bush, Jamie M; Enns, R Mark; Turner, A Simon

    2008-06-15

    Experimental study. To evaluate and compare the performances of 2 bioresorbable products, Mesofol (a caprolactone/lactide film) and Lactosorb (a polylactide film), as barriers to postoperative peridural adhesions and fibrosis. Postoperative peridural adhesions from scar tissue may be an inciting cause of chronic pain and dysfunction in "failed back" syndrome. Many biocompatible products and drugs, as well as autografts have been tested as antiadhesion barriers with varying success. The bioresorbable film products were used to cover large laminectomy defects in 11 sheep. Three laminectomy defects were created, with 2 randomly assigned treatment sites and 1 control site in each animal. A tear was created in the dura allowing cerebrospinal fluid leakage to assess for impaired dural healing. Performance of the film barriers was assessed at 10 weeks postoperative by gross scar and tenacity scoring by 3 blinded, independent observers in 7 animals. Histology was performed in 4 animals. New Methylene blue dye myelography and magnetic resonance imaging were performed to assess for cerebrospinal fluid leakage. Magnetic resonance imaging was also used to evaluate the imaging characteristics of adhesions. All 3 products evaluated showed a benefit to prevention of postoperative peridural adhesion; the performance of Mesofol was deemed superior to either of the 2 Lactosorb products. The handling characteristics of all products were compatible with clinical usage. Impairment to healing of dural tears or active inflammation was not identified with any product. The results of this investigation support previous studies on the benefit of polylactide film barriers, like Lactosorb, for reducing peridural adhesion following spinal surgery. The performance of Mesofol in this investigation suggests that it may provide improved antiadhesion properties in comparison to the polylactide products. Safety issues related to impaired dural healing was not identified in either product.

  4. Comparison between conventional and "clinical" assessment of experimental lung fibrosis

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    McClelland Grant B

    2008-04-01

    Full Text Available Abstract Background Idiopathic pulmonary fibrosis (IPF is a treatment resistant disease with poor prognosis. Numerous compounds have been demonstrated to efficiently prevent pulmonary fibrosis (PF in animal models but only a few were successful when given to animals with established fibrosis. Major concerns of current PF models are spontaneous resolution and high variability of fibrosis, and the lack of assessment methods that can allow to monitor the effect of drugs in individual animals over time. We used a model of experimental PF in rats and compare parameters obtained in living animals with conventional assessment tools that require removal of the lungs. Methods PF was induced in rats by adenoviral gene transfer of transforming growth factor-beta. Morphological and functional changes were assessed for up to 56 days by micro-CT, lung compliance (measured via a mechanical ventilator and VO2max and compared to histomorphometry and hydroxyproline content. Results Standard histological and collagen assessment confirmed the persistent fibrotic phenotype as described before. The histomorphological scores correlated both to radiological (r2 = 0.29, p 2 = 0.51, p 2max did not correlate with fibrosis. Conclusion The progression of pulmonary fibrosis can be reliably assessed and followed in living animals over time using invasive, non-terminal compliance measurements and micro-CT. This approach directly translates to the management of patients with IPF and allows to monitor therapeutic effects in drug intervention studies.

  5. Espondilodiscitis secundaria a anestesia peridural Spondilodiscitis secondary to peridural anesthesia

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    Yvei González Orlandi

    2010-12-01

    Full Text Available Se presenta el caso de un paciente con espondilodiscitis secundaria al uso de anestesia peridural lumbar para la resección transuretral de una hiperplasia fibroadenomatosa de la próstata. El cuadro clínico estuvo determinado por lumbalgia aguda con incremento progresivo que llevó al confinamiento en cama del paciente. En el examen físico del sistema osteomioarticular predominó la contractura paravertebral lumbar, así como en la palpación de esta región. En el examen neurológico no se encontraron alteraciones. La tomografía axial computarizada multicorte, así como la gammagrafía ósea de columna lumbar, confirmaron el diagnóstico. Se indicó tratamiento médico basado en los síntomas, antibioticoterapia combinada y ortesis externa. La recuperación total del paciente ocurrió a los 6 meses del inicio de la enfermedad.This is the case of a patient presenting with spondilodiscitis secondary to use of lumbar peridural anesthesia for transurethral resection of a prostatic fibroadenoma hyperplasia The clinical picture was determined by a acute lumbar pain with a progressive increase leading to put to bed the patient. In physical examination of osteomyoarticular system there was predominance of lumbar paravertebral contracture, as well as in palpation of this region. In neurological examination there weren't alterations. The multi-scan computed axial tomography and the spine column bone scintigraphy confirmed the diagnosis. Medical treatment was prescribed based on symptoms, combined antibiotic drug therapy and external orthesis. The total recovery of patient occurred at 6 months from the onset of disease.

  6. Effect of Pistacia lentiscus oil on experimental pulmonary fibrosis.

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    Abidi, Anouar; Serairi Beji, Raja; Kourda, Nadia; Ennigrou, Samir; Ksouri, Riadh; Jameleddine, Saloua

    2016-07-01

    Background - Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by histopathological lesions in lung tissue. This is the most common and most severe idiopathic interstitial pneumonias. Current treatments are based on the combination of corticosteroids and immunosuppressants, but their effectiveness is still debated. Purpose of work - Testing the preventive effect of Pistacia Lentiscus oil, known for its antioxidant, anti-mutagenic and anti-proliferative effects, on a model of experimental lung fibrosis. Methods - Two groups of rats received an intratracheal injection of bleomycin (4.5 mg / kg). The first group, control (n = 20 rats), has received no treatment. The second group was treated with Pistacia Lentiscus oil (n = 20 rats) for 30 days before fibrosis induction, by daily gavage oil Pistacia Lentiscus oil (3,33ml / kg). This treatment was continued for 10 days. At the end of the experimental period, all rats were sacrificed and the lung tissue was examined histopathologically and immunostained for TGFβ. Results - The chromatographic profile oil Pistacia Lentiscus oil shows the dominance of two fatty acids that are linoleic acid and palmitic acid representing respectively 70.57 and 24.67%. Our results also show a decrease in the distribution of TGFβ both at the level of the inflammatory infiltrate and at the level of the pulmonary parenchyma histiocytes of rats treated with Pistacia Lentiscus oil compared with control rats. However, these changes are not accompanied by statistically significant changes of fibrosis score and inflammatory index. Conclusion - Our results are interesting to consider. Further studies using higher doses of Pistacia Lentiscus oil are important to conduct.

  7. Abscesso peridural após analgesia controlada pelo paciente por via peridural: relato de caso

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    Abreu Múcio Paranhos de

    2004-01-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A analgesia peridural é freqüentemente utilizada para o controle da dor pós-operatória ou para tratamento da dor crônica em pacientes oncológicos. No entanto, não está isenta de complicações. Neste caso, relatamos a ocorrência de abscesso peridural em paciente jovem, hígida, que foi submetida a analgesia peridural em bomba de infusão controlada pela paciente, que apresentou abscesso peridural, sendo necessária descompressão cirúrgica. RELATO DO CASO: Paciente do sexo feminino, 24 anos, 56 kg, 1,65 m, estado físico ASA I, com história de lombalgia e dificuldade de flexão da coxa esquerda, foi submetida à cirurgia para liberação da musculatura posterior do quadril. Três dias após a alta hospitalar retornou ao hospital queixando-se de dor no local da incisão cirúrgica e durante a realização dos exercícios fisioterápicos. Foi internada e programada analgesia controlada pelo paciente (ACP por via peridural, para possibilitar o tratamento fisioterápico. No centro cirúrgico foi feita sedação por via venosa com midazolam (2,5 mg e fentanil (25 µg, anti-sepsia da pele e realizada punção peridural no espaço L3-L4. Após dose teste foram injetados ropivacaína a 0,75% (75 mg e fentanil (100 µg e passado cateter peridural em sentido cefálico, sem intercorrências. Foi instalada bomba de ACP contendo solução fisiológica a 0,9% (85 ml, bupivacaína a 0,5% (25 mg e fentanil (500 µg, programada com fluxo constante de 4 ml.h-1 e bolus de 2 ml a cada 20 minutos. No 3º dia a paciente relatou incômodo no local da inserção do cateter, sendo o mesmo retirado. Havia discreta hiperemia no local. Após vinte e dois dias, a paciente retornou ao hospital com dor de grande intensidade na região lombossacra com irradiação para os membros inferiores e limitação dos movimentos. Não havia deficit neurológico ou sinais flogísticos no local da punção ou na ferida operatória. Foi feita hip

  8. Experimental Model of Intervertebral Disk Mediated Postoperative Epidural Fibrosis.

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    Larionov, Sergey N; Sorokovikov, V A; Erdyneyev, K C; Lepekhova, S A; Goldberg, O A

    2016-07-01

    Postoperative epidural fibrosis (EF) after lumbar discectomy is the most common and at the same time controversial issue. The etiology and pathogenesis creates a lot of discussion and selection of methods of treatment and prevention continues. LIV laminectomy with dura mater (DM) exposition was done in 24 rats, and then, 0.3 ml of elements of suspension of autologous intervertebral disk was implicated on DM. As autologous intervertebral disk, we used the intervertebral disk from amputated tail. In all the animals, incisions were closed with 3/0 Vicryl. EF was examined. Fibroblast cell density was calculated in each field at ×40 magnification: Grade 1 - fewer than 100 fibroblasts in each field; Grade 2 - 100-150 fibroblasts in each field; Grade 3 - more than 150 fibroblasts in each field. Based on histological results, we confirmed our model of experiment. On the 30th day of evaluation, there were significant histological evidences of postoperative epidural adhesions in experimental animals, which included the obliteration of epidural space, the presence of adhesions in the dura and nerve roots, the restructuring of the yellow ligament, bone sclerosis, excessive appearance of fibrous tissue around the autologous intervertebral disk tissue that applied on the DM. In our work, we describe a new experimental model, where the elements of autologous intervertebral disk play the role of inflammation trigger, which cause postoperative scar and EF.

  9. Therapy of experimental NASH and fibrosis with galectin inhibitors.

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    Peter G Traber

    Full Text Available Non-alcoholic steatohepatitis (NASH and resultant liver fibrosis is a major health problem without effective therapy. Some data suggest that galectin-3 null mice are resistant to the development of NASH with fibrosis. We examined the ability of two complex carbohydrate drugs that bind galectin-3, GM-CT-01 and GR-MD-02, to treat NASH with fibrosis in a murine model. GR-MD-02 treatment resulted in marked improvement in liver histology with significant reduction in NASH activity and collagen deposition. Treatments seemed also to improve both glomerulopathy and interstitial fibrosis observed in kidneys. The improvement in liver histology was evident when animals were treated early in disease or after establishment of liver fibrosis. In all measures, GM-CT-01 had an intermediate effect between vehicle and GR-MD-02. Galectin-3 protein expression was increased in NASH with highest expression in macrophages surrounding lipid laden hepatocytes, and reduced following treatment with GR-MD-02, while the number of macrophages was unchanged. Treatment with GR-MD-02 also reduced the expression of pathological indicators including iNOS, an important TH1 inflammatory mediator, CD36, a scavenger receptor for lipoproteins on macrophages, and α-smooth muscle actin, a marker for activated stellate cells which are the primary collagen producing cells in liver fibrosis. We conclude that treatment with these galectin-3 targeting drugs improved histopathological findings of NASH and markedly reduced fibrosis in a murine model of NASH. While the mechanisms require further investigation, the treatment effect is associated with a reduction of galectin-3 expressed by activated macrophages which was associated with regression of NASH, including hepatocellular fat accumulation, hepatocyte ballooning, intra-portal and intra-lobular inflammatory infiltrate, and deposition of collagen. Similar effects were found with GM-CT-01, but with approximately four-fold lower potency than

  10. An Experimental Approach to the Pathogenesis of "Pipestem" Fibrosis (Symmers' Fibrosis of the Liver

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    Zilton A Andrade

    1997-09-01

    Full Text Available Pathogenesis of schistosomal hepatic fibrosis ("pipestem" fibrosis of the liver was investigated by means of the murine model. Although worm load appears as the main pathogenetic factor, alone it is not sufficient to produce that characteristic lesion. By comparing the findings in animals with heavy and prolonged Schistosoma mansoni infection, which developed or not" pipestem" fibrosis, it was observed that the lesion was more frequent in intact animals than in the splenectomized one. However, the size of the spleen, the number of recovered worms, the number of eggs per gram of liver tissue, the level of serum idiotype and anti-idiotype antibodies, the size and volume of periovular granulomas formed in the liver, all that failed to show statistically significant differences between the two groups. After analysing all these data, other factors, that apparently have been hitherto negleted, rested to explain the findings. Among them, the timing and sequence of the egg-induced intrahepatic vascular changes seemed crucial. The sequential development of intrahepatic portal vein obstruction, followed by the opening of periportal collateral veins and the continous arrival of schistosome eggs going to be lodged into the latter, appeared as essential steps in the pathogenesis of "pipestem" fibrosis

  11. Bosutinib Therapy Ameliorates Lung Inflammation and Fibrosis in Experimental Silicosis.

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    Carneiro, Priscila J; Clevelario, Amanda L; Padilha, Gisele A; Silva, Johnatas D; Kitoko, Jamil Z; Olsen, Priscilla C; Capelozzi, Vera L; Rocco, Patricia R M; Cruz, Fernanda F

    2017-01-01

    Silicosis is an occupational lung disease for which no effective therapy exists. We hypothesized that bosutinib, a tyrosine kinase inhibitor, might ameliorate inflammatory responses, attenuate pulmonary fibrosis, and thus improve lung function in experimental silicosis. For this purpose, we investigated the potential efficacy of bosutinib in the treatment of experimental silicosis induced in C57BL/6 mice by intratracheal administration of silica particles. After 15 days, once disease was established, animals were randomly assigned to receive DMSO or bosutinib (1 mg/kg/dose in 0.1 mL 1% DMSO) by oral gavage, twice daily for 14 days. On day 30, lung mechanics and morphometry, total and differential cell count in alveolar septa and granuloma, levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-4, transforming growth factor (TGF)-β, and vascular endothelial growth factor in lung homogenate, M1 and M2 macrophages, total leukocytes, and T cells in BALF, lymph nodes, and thymus, and collagen fiber content in alveolar septa and granuloma were analyzed. In a separate in vitro experiment, RAW264.7 macrophages were exposed to silica particles in the presence or absence of bosutinib. After 24 h, gene expressions of arginase-1, IL-10, IL-12, inducible nitric oxide synthase (iNOS), metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1, and caspase-3 were evaluated. In vivo, in silicotic animals, bosutinib, compared to DMSO, decreased: (1) fraction area of collapsed alveoli, (2) size and number of granulomas, and mononuclear cell granuloma infiltration; (3) IL-1β, TNF-α, IFN-γ, and TGF-β levels in lung homogenates, (4) collagen fiber content in lung parenchyma, and (5) viscoelastic pressure and static lung elastance. Bosutinib also reduced M1 cell counts while increasing M2 macrophage population in both lung parenchyma and granulomas. Total leukocyte, regulatory T, CD4+, and CD8+ cell counts in the lung-draining lymph

  12. Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension.

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    Martínez-Martínez, Ernesto; Calvier, Laurent; Fernández-Celis, Amaya; Rousseau, Elodie; Jurado-López, Raquel; Rossoni, Luciana V; Jaisser, Frederic; Zannad, Faiez; Rossignol, Patrick; Cachofeiro, Victoria; López-Andrés, Natalia

    2015-10-01

    Hypertensive cardiac remodeling is accompanied by molecular inflammation and fibrosis, 2 mechanisms that finally affect cardiac function. At cardiac level, aldosterone promotes inflammation and fibrosis, although the precise mechanisms are still unclear. Galectin-3 (Gal-3), a β-galactoside-binding lectin, is associated with inflammation and fibrosis in the cardiovascular system. We herein investigated whether Gal-3 inhibition could block aldosterone-induced cardiac inflammation and fibrosis and its potential role in cardiac damage associated with hypertension. Aldosterone-salt-treated rats presented hypertension, cardiac inflammation, and fibrosis that were prevented by the pharmacological inhibition of Gal-3 with modified citrus pectin. Cardiac inflammation and fibrosis presented in spontaneously hypertensive rats were prevented by modified citrus pectin treatment, whereas Gal-3 blockade did not modify blood pressure levels. In the absence of blood pressure modifications, Gal-3 knockout mice were resistant to aldosterone-induced cardiac inflammation. In human cardiac fibroblasts, aldosterone increased Gal-3 expression via its mineralocorticoid receptor. Gal-3 and aldosterone enhanced proinflammatory and profibrotic markers, as well as metalloproteinase activities in human cardiac fibroblasts, effects that were not observed in Gal-3-silenced cells treated with aldosterone. In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac inflammation and fibrosis, alterations that were prevented by Gal-3 blockade independently of blood pressure levels. These data suggest that Gal-3 could be a new molecular mechanism linking cardiac inflammation and fibrosis in situations with high-aldosterone levels, such as hypertension. © 2015 American Heart Association, Inc.

  13. Experimental induction of pulmonary fibrosis in horses with the gammaherpesvirus equine herpesvirus 5.

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    Williams, Kurt J; Robinson, N Edward; Lim, Ailam; Brandenberger, Christina; Maes, Roger; Behan, Ashley; Bolin, Steven R

    2013-01-01

    Gammaherpesviruses (γHV) are implicated in the pathogenesis of pulmonary fibrosis in humans and murine models of lung fibrosis, however there is little direct experimental evidence that such viruses induce lung fibrosis in the natural host. The equine γHV EHV 5 is associated with equine multinodular pulmonary fibrosis (EMPF), a progressive fibrosing lung disease in its natural host, the horse. Experimental reproduction of EMPF has not been attempted to date. We hypothesized that inoculation of EHV 5 isolated from cases of EMPF into the lungs of clinically normal horses would induce lung fibrosis similar to EMPF. Neutralizing antibody titers were measured in the horses before and after inoculation with EHV 5. PCR and virus isolation was used to detect EHV 5 in antemortem blood and BAL samples, and in tissues collected postmortem. Nodular pulmonary fibrosis and induction of myofibroblasts occurred in EHV 5 inoculated horses. Mean lung collagen in EHV 5 inoculated horses (80 µg/mg) was significantly increased compared to control horses (26 µg/mg) (p < 0.5), as was interstitial collagen (32.6% ± 1.2% vs 23% ± 1.4%) (mean ± SEM; p < 0.001). Virus was difficult to detect in infected horses throughout the experiment, although EHV 5 antigen was detected in the lung by immunohistochemistry. We conclude that the γHV EHV 5 can induce lung fibrosis in the horse, and hypothesize that induction of fibrosis occurs while the virus is latent within the lung. This is the first example of a γHV inducing lung fibrosis in the natural host.

  14. Renal Fibrosis mRNA Classifier: Validation in Experimental Lithium-Induced Interstitial Fibrosis in the Rat Kidney.

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    Marti, Hans-Peter; Jeffs, Aaron; Scherer, Andreas; Leader, John; Leader, Catherine; Bedford, Jennifer; Walker, Robert

    2016-01-01

    Accurate diagnosis of fibrosis is of paramount clinical importance. A human fibrosis classifier based on metzincins and related genes (MARGS) was described previously. In this investigation, expression changes of MARGS genes were explored and evaluated to examine whether the MARGS-based algorithm has any diagnostic value in a rat model of lithium nephropathy. Male Wistar rats (n = 12) were divided into 2 groups (n = 6). One group was given a diet containing lithium (40 mmol/kg food for 7 days, followed by 60mmol/kg food for the rest of the experimental period), while a control group (n = 6) was fed a normal diet. After six months, animals were sacrificed and the renal cortex and medulla of both kidneys removed for analysis. Gene expression changes were analysed using 24 GeneChip® Affymetrix Rat Exon 1.0 ST arrays. Statistically relevant genes (p-value1.5, t-test) were further examined. Matrix metalloproteinase-2 (MMP2), CD44, and nephroblastoma overexpressed gene (NOV) were overexpressed in the medulla and cortex of lithium-fed rats compared to the control group. TGFβ2 was overrepresented in the cortex of lithium-fed animals 1.5-fold, and 1.3-fold in the medulla of the same animals. In Gene Set Enrichment Analysis (GSEA), both the medulla and cortex of lithium-fed animals showed an enrichment of the MARGS, TGFβ network, and extracellular matrix (ECM) gene sets, while the cortex expression signature was enriched in additional fibrosis-related-genes and the medulla was also enriched in immune response pathways. Importantly, the MARGS-based fibrosis classifier was able to classify all samples correctly. Immunohistochemistry and qPCR confirmed the up-regulation of NOV, CD44, and TGFβ2. The MARGS classifier represents a cross-organ and cross-species classifier of fibrotic conditions and may help to design a test to diagnose and to monitor fibrosis. The results also provide evidence for a common pathway in the pathogenesis of fibrosis.

  15. Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis.

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    Cruz, Fernanda Ferreira; Horta, Lucas Felipe Bastos; Maia, Lígia de Albuquerque; Lopes-Pacheco, Miquéias; da Silva, André Benedito; Morales, Marcelo Marco; Gonçalves-de-Albuquerque, Cassiano Felippe; Takiya, Christina Maeda; de Castro-Faria-Neto, Hugo Caire; Rocco, Patricia Rieken Macedo

    2016-01-01

    Silicosis is an occupational lung disease with no effective treatment. We hypothesized that dasatinib, a tyrosine kinase inhibitor, might exhibit therapeutic efficacy in silica-induced pulmonary fibrosis. Silicosis was induced in C57BL/6 mice by a single intratracheal administration of silica particles, whereas the control group received saline. After 14 days, when the disease was already established, animals were randomly assigned to receive DMSO or dasatinib (1 mg/kg) by oral gavage, twice daily, for 14 days. On day 28, lung morphofunction, inflammation, and remodeling were investigated. RAW 264.7 cells (a macrophage cell line) were incubated with silica particles, followed by treatment or not with dasatinib, and evaluated for macrophage polarization. On day 28, dasatinib improved lung mechanics, increased M2 macrophage counts in lung parenchyma and granuloma, and was associated with reduction of fraction area of granuloma, fraction area of collapsed alveoli, protein levels of tumor necrosis factor-α, interleukin-1β, transforming growth factor-β, and reduced neutrophils, M1 macrophages, and collagen fiber content in lung tissue and granuloma in silicotic animals. Additionally, dasatinib reduced expression of iNOS and increased expression of arginase and metalloproteinase-9 in silicotic macrophages. Dasatinib was effective at inducing macrophage polarization toward the M2 phenotype and reducing lung inflammation and fibrosis, thus improving lung mechanics in a murine model of acute silicosis.

  16. Quebra de cateter no espaço peridural

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    Cristian Sbardelotto; Mauro Matsumoto Yoshimi; Raquel da Rocha Pereira; Renato Almeida Couto de Castro

    2008-01-01

    JUSTIFICATIVA E OBJETIVOS: A quebra do cateter peridural durante sua remoção é rara, porém descrita. O conhecimento das possíveis complicações e o manuseio adequado são responsabilidades do anestesiologista. O objetivo deste relato foi apresentar caso de quebra de cateter peridural em analgesia de parto. RELATO DO CASO: Paciente do sexo feminino, 33 anos, GII, PI, deu entrada na maternidade em trabalho de parto. Após duas horas de evolução, a paciente solicitou analgesia. Ao exame, encontrava...

  17. Role of IL-1β in experimental cystic fibrosis upon P. aeruginosa Infection

    NARCIS (Netherlands)

    J. Palomo (Jennifer); T. Marchiol (Tiffany); J. Piotet (Julie); L. Fauconnier (Louis); M. Robinet (Marieke); F. Reverchon (Flora); M.L. Bert (Marc Le); D. Togbe (Dieudonné); R.M. Buijs-Offerman (Ruvalic); M. Stolarczyk (Marta); V.R.F.J. Quesniaux (Valé Rie F. J.); B.J. Scholte (Bob); B. Ryffel (Bernhard)

    2014-01-01

    textabstractCystic fibrosis is associated with increased inflammatory responses to pathogen challenge. Here we revisited the role of IL-1β in lung pathology using the experimental F508del-CFTR murine model on C57BL/6 genetic background (Cftrtm1eur or d/d), on double deficient for d/d and type 1

  18. Experimental liver fibrosis research: update on animal models, legal issues and translational aspects

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    2013-01-01

    Liver fibrosis is defined as excessive extracellular matrix deposition and is based on complex interactions between matrix-producing hepatic stellate cells and an abundance of liver-resident and infiltrating cells. Investigation of these processes requires in vitro and in vivo experimental work in animals. However, the use of animals in translational research will be increasingly challenged, at least in countries of the European Union, because of the adoption of new animal welfare rules in 2013. These rules will create an urgent need for optimized standard operating procedures regarding animal experimentation and improved international communication in the liver fibrosis community. This review gives an update on current animal models, techniques and underlying pathomechanisms with the aim of fostering a critical discussion of the limitations and potential of up-to-date animal experimentation. We discuss potential complications in experimental liver fibrosis and provide examples of how the findings of studies in which these models are used can be translated to human disease and therapy. In this review, we want to motivate the international community to design more standardized animal models which might help to address the legally requested replacement, refinement and reduction of animals in fibrosis research. PMID:24274743

  19. Adrenomedullin in inflammatory process associated with experimental pulmonary fibrosis

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    Bramanti Placido

    2011-04-01

    Full Text Available Abstract Background Adrenomedullin (AM, a 52-amino acid ringed-structure peptide with C-terminal amidation, was originally isolated from human pheochromocytoma. AM are widely distributed in various tissues and acts as a local vasoactive hormone in various conditions. Methods In the present study, we investigated the efficacy of AM on the animal model of bleomycin (BLM-induced lung injury. Mice were subjected to intratracheal administration of BLM and were assigned to receive AM daily by an intraperitoneal injection of 200 ngr/kg. Results and Discussion Myeloperoxidase activity, lung histology, immunohistochemical analyses for cytokines and adhesion molecules expression, inducible nitric oxide synthase (iNOS, nitrotyrosine, and poly (ADP-ribose polymerase (PARP were performed one week after fibrosis induction. Lung histology and transforming growth factor beta (TGF-β were performed 14 and 21 days after treatments. After bleomycin administration, AM-treated mice exhibited a reduced degree of lung damage and inflammation compared with BLM-treated mice, as shown by the reduction of (1 myeloperoxidase activity (MPO, (2 cytokines and adhesion molecules expression, (3 nitric oxide synthase expression, (4 the nitration of tyrosine residues, (5 poly (ADP-ribose (PAR formation, a product of the nuclear enzyme poly (ADP-ribose polymerase (PARP (6 transforming growth factor beta (TGF-β (7and the degree of lung injury. Conclusions Our results indicate that AM administration is able to prevent bleomycin induced lung injury through the down regulation of proinflammatory factors.

  20. Experimental systems to study the origin of the myofibroblast in peritoneal fibrosis

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    Manreet Padwal

    2016-09-01

    Full Text Available Peritoneal fibrosis is one of the major complications occurring in long-term peritoneal dialysis patients as a result of injury. Peritoneal fibrosis is characterized by submesothelial thickening and fibrosis which is associated with a decline in peritoneal membrane function. The myofibroblast has been identified as the key player involved in the development and progression of peritoneal fibrosis. Activation of the myofibroblast is correlated with expansion of the extracellular matrix and changes in peritoneal membrane integrity. Over the years, epithelial to mesenchymal transition (EMT has been accepted as the predominant source of the myofibroblast. Peritoneal mesothelial cells have been described to undergo EMT in response to injury. Several animal and in vitro studies support the role of EMT in peritoneal fibrosis; however, emerging evidence from genetic fate-mapping studies has demonstrated that myofibroblasts may be arising from resident fibroblasts and pericytes/perivascular fibroblasts. In this review, we will discuss hypotheses currently surrounding the origin of the myofibroblast and highlight the experimental systems predominantly being used to investigate this.

  1. Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Liang, E-mail: countryspring@sina.com; Ji, Yunxia, E-mail: 413499057@qq.com; Kang, Zechun, E-mail: davidjiangwl@163.com; Lv, Changjun, E-mail: Lucky_lcj@sina.com; Jiang, Wanglin, E-mail: jwl518@163.com

    2015-02-15

    An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial–mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, α-smooth muscle actin (α-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1 and the regulation of RAGE, PA reversed the EMT, inhibited HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. - Highlights: • PA prevents EMT, reduces the apoptosis of AT1 in vitro. • PA decreases proliferation of HLF-1, reduces PDGF and FGF expression in vitro. • PA prevents experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

  2. TAK1 inhibition attenuates both inflammation and fibrosis in experimental pneumoconiosis.

    Science.gov (United States)

    Li, Jie; Liang, Chao; Zhang, Zong-Kang; Pan, Xiaohua; Peng, Songlin; Lee, Wing-Sze; Lu, Aiping; Lin, Zhixiu; Zhang, Ge; Leung, Wing-Nang; Zhang, Bao-Ting

    2017-01-01

    Pneumoconiosis, caused by inhalation of mineral dusts, is a major occupational disease worldwide. Currently, there are no effective drugs owing to a lack of potential therapeutic targets during either the inflammation or fibrosis molecular events in pneumoconiosis. Here, we performed microarrays to identify aberrantly expressed genes in the above molecular events in vitro and found a hub gene transforming growth factor-β-activated kinase 1 (TAK1), which was highly expressed and activated in pneumoconiosis patients as well as silica-exposed rats with experimental pneumoconiosis. Genetic modulation of TAK1 by CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9, RNA interference and overexpression indicated the important role of TAK1 in both inflammation and fibrosis in experimental pneumoconiosis. To achieve pharmacological TAK1 inhibition, we virtually screened out a natural product resveratrol, which targeted TAK1 at both N161 and A107 residues, and significantly inhibited TAK1 activation to attenuate inflammation and fibrosis in vitro. Consistently, in vivo prevention and intervention studies showed that resveratrol could inhibit pulmonary inflammation and fibrosis in silica-exposed rats.

  3. Nrf2 and Snail-1 in the prevention of experimental liver fibrosis by caffeine.

    Science.gov (United States)

    Gordillo-Bastidas, Daniela; Oceguera-Contreras, Edén; Salazar-Montes, Adriana; González-Cuevas, Jaime; Hernández-Ortega, Luis Daniel; Armendáriz-Borunda, Juan

    2013-12-21

    To determine the molecular mechanisms involved in experimental hepatic fibrosis prevention by caffeine (CFA). Liver fibrosis was induced in Wistar rats by intraperitoneal thioacetamide or bile duct ligation and they were concomitantly treated with CFA (15 mg/kg per day). Fibrosis and inflammatory cell infiltrate were evaluated and classified by Knodell index. Inflammatory infiltrate was quantified by immunohistochemistry (anti-CD11b). Gene expression was analyzed by quantitative reverse transcription-polymerase chain reaction for collagen I (Col-1), connective tissue growth factor (CTGF), transforming growth factor β1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, superoxide dismutase (SOD) and catalase (CAT). Activation of Nrf2 and Snail-1 was analyzed by Western-blot. TNF-α expression was proved by enzyme-linked immunosorbant assay, CAT activity was performed by zymography. CFA treatment diminished fibrosis index in treated animals. The Knodell index showed both lower fibrosis and necroinflammation. Expression of profibrogenic genes CTGF, Col-1 and TGF-β1 and proinflammatory genes TNF-α, IL-6 and IL-1 was substantially diminished with CFA treatment with less CD11b positive areas. Significantly lower values of transcriptional factor Snail-1 were detected in CFA treated rats compared with cirrhotic rats without treatment; in contrast Nrf2 was increased in the presence of CFA. Expression of SOD and CAT was greater in animals treated with CFA showing a strong correlation between mRNA expression and enzyme activity. Our results suggest that CFA inhibits the transcriptional factor Snail-1, down-regulating profibrogenic genes, and activates Nrf2 inducing antioxidant enzymes system, preventing inflammation and fibrosis.

  4. Protective roles of pulmonary rehabilitation mixture in experimental pulmonary fibrosis in vitro and in vivo

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    Zhang, L.; Ji, Y.X.; Jiang, W.L.; Lv, C.J. [School of Pharmaceutical Sciences, Binzhou Medical University, Yantai (China)

    2015-05-08

    Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (PRM), which combines extracts from eight traditional Chinese medicines, has very good lung protection in clinical use. However, it is not known if PRM has anti-fibrotic activity. In this study, we investigated the effects of PRM on transforming growth factor-β1 (TGF-β1)-mediated and bleomycin (BLM)-induced pulmonary fibrosis in vitro and in vivo. The effects of PRM on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on BLM-induced pulmonary fibrosis in vivo were investigated. PRM treatment resulted in a reduction of EMT in A549 cells that was associated with attenuating an increase of vimentin and a decrease of E-cadherin. PRM inhibited the proliferation of HLF-1 at an IC{sub 50} of 0.51 µg/mL. PRM ameliorated BLM-induced pulmonary fibrosis in rats, with reduction of histopathological scores and collagen deposition, and a decrease in α-smooth muscle actin (α-SMA) and HMGB1 expression. An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs. PRM significantly decreased EMT and prevented pulmonary fibrosis through decreasing HMGB1 and regulating RAGE in vitro and in vivo. PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels. In summary, PRM prevented experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

  5. Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo.

    Science.gov (United States)

    Lehmann, Mareike; Korfei, Martina; Mutze, Kathrin; Klee, Stephan; Skronska-Wasek, Wioletta; Alsafadi, Hani N; Ota, Chiharu; Costa, Rita; Schiller, Herbert B; Lindner, Michael; Wagner, Darcy E; Günther, Andreas; Königshoff, Melanie

    2017-08-01

    Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor prognosis and limited therapeutic options. The incidence of IPF increases with age, and ageing-related mechanisms such as cellular senescence have been proposed as pathogenic drivers. The lung alveolar epithelium represents a major site of tissue injury in IPF and senescence of this cell population is probably detrimental to lung repair. However, the potential pathomechanisms of alveolar epithelial cell senescence and the impact of senolytic drugs on senescent lung cells and fibrosis remain unknown. Here we demonstrate that lung epithelial cells exhibit increased P16 and P21 expression as well as senescence-associated β-galactosidase activity in experimental and human lung fibrosis tissue and primary cells.Primary fibrotic mouse alveolar epithelial type (AT)II cells secreted increased amounts of senescence-associated secretory phenotype (SASP) factors in vitro, as analysed using quantitative PCR, mass spectrometry and ELISA. Importantly, pharmacological clearance of senescent cells by induction of apoptosis in fibrotic ATII cells or ex vivo three-dimensional lung tissue cultures reduced SASP factors and extracellular matrix markers, while increasing alveolar epithelial markers.These data indicate that alveolar epithelial cell senescence contributes to lung fibrosis development and that senolytic drugs may be a viable therapeutic option for IPF. Copyright ©ERS 2017.

  6. Peridural analgesia may affect long-term survival in patients with colorectal cancer after surgery (PACO-RAS-Study): an analysis of a cancer registry.

    Science.gov (United States)

    Holler, Julia P N; Ahlbrandt, Janko; Burkhardt, Ernst; Gruss, Marco; Röhrig, Rainer; Knapheide, Julia; Hecker, Andreas; Padberg, Winfried; Weigand, Markus A

    2013-12-01

    To determine the effect of peridural analgesia on long-term survival in patients who underwent surgical treatment of colorectal carcinoma. Clinical and animal studies suggest a potential benefit of peridural analgesia on morbidity and mortality after cancer surgery. The effect of peridural analgesia on long-term outcome after surgery for colorectal cancer remains undefined. From 2003 to 2009, there were 749 patients who underwent surgery for colorectal carcinoma under general anesthesia with or without peridural analgesia. Clinical data were reviewed retrospectively and analyzed with multivariate analysis and Kaplan-Meier plots. There were 442 patients who received peridural analgesia and 307 patients who did not receive peridural analgesia. A substantial survival benefit was observed in patients who received peridural analgesia (5-year survival rate: peridural analgesia, 62%; no peridural analgesia, 54%; P < 0.02). The hazard rate for death was decreased by 27% in patients who received peridural analgesia. When peridural analgesia was included simultaneously in a Cox model with the confounding factors age, American Society of Anesthesiologists classification, and stage, there was a significant survival benefit in patients who received peridural analgesia. In patients with America Society of Anesthesiologists classification 3 to 4, there was significantly greater survival with peridural analgesia than without peridural analgesia (P < 0.009). Peridural analgesia may improve survival in patients underwent surgery for colorectal carcinoma. The survival benefit with peridural analgesia was greater in patients who had greater medical morbidity.

  7. Protective activity of gallic acid against glyoxal -induced renal fibrosis in experimental rats

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    Mohammed Jainuddin Yousuf

    2015-01-01

    Full Text Available This study was designed to evaluate the protective activity of gallic acid (GA against glyoxal (GO an advanced glycation intermediate-induced renal fibrosis in experimental rats. Glyoxal (i.p at a dose of 15 mg/Kg body weight/day for 4 weeks induces renal fibrosis. GA was administered orally (100 mg/Kg body weight/day along with GO for 4 weeks. The anti-fibrotic activity of GA was analyzed by measuring the collagen synthesis and deposition in renal tissues using mRNA expression analysis and Masson trichrome staining (MTS, respectively. The nephroprotective potential of GA was assessed by quantifying the markers of kidney damage such as serum blood-urea-nitrogen (BUN, creatinine (CR and alkaline phosphatase (AP. Moreover, basement membrane damage in renal tissues was analysed by periodic acid Schiff’s (PAS staining. GA co-treatment markedly suppressed the GO-induced elevation in mRNA expression of collagen I and III, MMP-2, MMP-9 and NOX (p < 0.05, respectively genes as compared with GO alone infused rats. In addition, GA co-treatment significantly attenuated the GO -induced elevation in serum markers such as BUN, CR and AP levels (p < 0.05, respectively. Furthermore, GA co-treatment restored back the decreased renal super oxide dismutase (SOD activity (p < 0.05 thereby assuage the reactive oxygen species (ROS generation, and maintained the normal architecture of glomerulus. The present study clearly indicates that GO -induces renal fibrosis by enhancing GO/receptor of advanced glycation end product (RAGE induced ROS generation and GA effectively counteracted GO-induced renal fibrosis by its ROS quenching and anti-glycation activity.

  8. Efficacy of Poly(D,L-Lactic Acid-co-Glycolic acid)-Poly(Ethylene Glycol)-Poly(D,L-Lactic Acid-co-Glycolic Acid) Thermogel As a Barrier to Prevent Spinal Epidural Fibrosis in a Postlaminectomy Rat Model.

    Science.gov (United States)

    Li, Xiangqian; Chen, Lin; Lin, Hong; Cao, Luping; Cheng, Ji'an; Dong, Jian; Yu, Lin; Ding, Jiandong

    2017-04-01

    Experimental animal study. The authors conducted a study to determine the efficacy and safety of the poly(D,L-lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(D,L-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) thermogel to prevent peridural fibrosis in an adult rat laminectomy model. Peridural fibrosis often occurs after spinal laminectomy. It might cause persistent back and/or leg pain postoperatively and make a reoperation more difficult and dangerous. Various materials have been used to prevent epidural fibrosis, but only limited success has been achieved. The PLGA-PEG-PLGA thermogel was synthesized by us. Total L3 laminectomies were performed on 24 rats. The PLGA-PEG-PLGA thermogel or chitosan (CHS) gel (a positive control group) was applied to the operative sites in a blinded manner. In the control group, the L3 laminectomy was performed and the defect was irrigated with the NS solution 3 times. All the rats were killed 4 weeks after the surgery. The cytotoxicity of this thermogel was evaluated in vitro and the result demonstrated that no evidence of cytotoxicity was observed. The extent of epidural fibrosis, the area of epidural fibrosis, and the density of the fibroblasts and blood vessel were evaluated histologically. There were statistical differences among the PLGA-PEG-PLGA thermogel or CHS gel group compared with the control group. Although there was no difference between the PLGA-PEG-PLGA thermogel and CHS gel, the efficiency of the PLGA-PEG-PLGA thermogel was shown to be slightly improved compared with the CHS gel. The biocompatibility of the PLGA-PEG-PLGA thermogel was proven well. The application of this thermogel effectively reduced epidural scarring and prevented the subsequent adhesion to the dura mater. No side effects were noted in the rats.

  9. Overexpression of apolipoprotein A1 in the lung abrogates fibrosis in experimental silicosis.

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    Eun hee Lee

    Full Text Available The inhalation of silica particles induces silicosis, an inflammatory and fibrotic lung disease characterized by the early accumulation of macrophages and neutrophils in the airspace and subsequent appearance of silicotic nodules as a result of progressive fibrosis. This study evaluated whether apolipoprotein A1 (ApoA1 protects against ongoing fibrosis and promotes the resolution of established experimental lung silicosis. Crystallized silica was intratracheally administered to 6- to 8-week-old transgenic mice expressing human ApoA1 in their alveolar epithelial cells (day 0. ApoA1 was overexpressed beginning on day 7 (ApoA1_D7 group or day 15 (ApoA1_D15 group. The mice were sacrificed on day 30 for an evaluation of lung histology; the measurement of collagen, transforming growth factor-b1 and lipoxin A4; and a TUNEL assay for apoptotic cells. The ApoA1_D7 and D15 groups showed significant reductions in the silica-induced increase in inflammatory cells, silicotic nodule area, and collagen deposition compared with the silica-treated ApoA1 non-overexpressing mice. The level of transforming growth factor-b1 decreased in the bronchoalveolar lavage fluid, whereas lipoxin A4 was increased in the ApoA1_D7 and D15 groups compared with the silica-treated ApoA1 non-overexpressing mice. The silica-induced increase in the number of apoptotic cells was significantly reduced in the lungs of mice overexpressing ApoA1. Overexpression of ApoA1 decreased silica-induced lung inflammation and fibrotic nodule formation. The restoration of lipoxin A4 may contribute to the protective effect of ApoA1 overexpression against silica-induced lung fibrosis.

  10. Celecoxib treatment reduces peritoneal fibrosis and angiogenesis and prevents ultrafiltration failure in experimental peritoneal dialysis

    NARCIS (Netherlands)

    Fabbrini, Paolo; Schilte, Margot N.; Zareie, Mammad; ter Wee, Piet M.; Keuning, Eelco D.; Beelen, Robert H. J.; van den Born, Jaap

    2009-01-01

    Background. Daily peritoneal exposure to peritoneal dialysis fluid (PDF) induces severe morphological alterations including fibrosis and angiogenesis that lead to a loss of peritoneal ultrafiltration (UF) capacity. Since cyclooxygenase (COX)-2 is involved in fibrosis and angiogenesis, we

  11. A DPP-4 inhibitor suppresses fibrosis and inflammation on experimental autoimmune myocarditis in mice.

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    Hiroyuki Hirakawa

    Full Text Available Myocarditis is a critical inflammatory disorder which causes life-threatening conditions. No specific or effective treatment has been established. DPP-4 inhibitors have salutary effects not only on type 2 diabetes but also on certain cardiovascular diseases. However, the role of a DPP-4 inhibitor on myocarditis has not been investigated. To clarify the effects of a DPP-4 inhibitor on myocarditis, we used an experimental autoimmune myocarditis (EAM model in Balb/c mice. EAM mice were assigned to the following groups: EAM mice group treated with a DPP-4 inhibitor (linagliptin (n = 19 and those untreated (n = 22. Pathological analysis revealed that the myocardial fibrosis area ratio in the treated group was significantly lower than in the untreated group. RT-PCR analysis demonstrated that the levels of mRNA expression of IL-2, TNF-α, IL-1β and IL-6 were significantly lower in the treated group than in the untreated group. Lymphocyte proliferation assay showed that treatment with the DPP-4 inhibitor had no effect on antigen-induced spleen cell proliferation. Administration of the DPP-4 inhibitor remarkably suppressed cardiac fibrosis and reduced inflammatory cytokine gene expression in EAM mice. Thus, the agents present in DPP-4 inhibitors may be useful to treat and/or prevent clinical myocarditis.

  12. Relationship between fibrosis and lactate dehydrogenase isoenzymes in the experimental hypertrophic heart of rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Revis, N.W.; Cameron, A.J.V.

    1978-06-01

    Cardiac hypertrophy was induced in rabbits by injecting either thyroxine or isoprenaline or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the lactate dehydrogenase isoenzyme pattern and an increase in fibrosis (as measured by hydroxyproline concentrations). Isoprenaline treatment led to a moderate increase in heart weight, a marked decrease in the heart/skeletal muscle subunit ratio of lactate dehydrogenase, and a marked increase in hydroxyproline. Thyroxine treatment led to a small increase in both heart weight and hydroxyproline and a small decrease in the heart/skeletal muscle subunit ratio. Coarctation of the aorta, in contrast, caused a marked increase in heart weight, a moderate decrease in heart/skeletal muscle subunit ratio, and a moderate increase in hydroxyproline. These results suggest that the decrease in the heart/skeletal muscle subunit ratio of lactate dehydrogenase in the experimental hypertrophic heart reflects the extent of myocardial fibrosis, rather than changes within the hypertrophied myocardial cells.

  13. Anti-melanin-concentrating hormone treatment attenuates chronic experimental colitis and fibrosis.

    Science.gov (United States)

    Ziogas, Dimitrios C; Gras-Miralles, Beatriz; Mustafa, Sarah; Geiger, Brenda M; Najarian, Robert M; Nagel, Jutta M; Flier, Sarah N; Popov, Yury; Tseng, Yu-Hua; Kokkotou, Efi

    2013-05-15

    Fibrosis represents a major complication of several chronic diseases, including inflammatory bowel disease (IBD). Treatment of IBD remains a clinical challenge despite several recent therapeutic advances. Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide shown to regulate appetite and energy balance. However, accumulating evidence suggests that MCH has additional biological effects, including modulation of inflammation. In the present study, we examined the efficacy of an MCH-blocking antibody in treating established, dextran sodium sulfate-induced experimental colitis. Histological and molecular analysis of mouse tissues revealed that mice receiving anti-MCH had accelerated mucosal restitution and lower colonic expression of several proinflammatory cytokines, as well as fibrogenic genes, including COL1A1. In parallel, they spared collagen deposits seen in the untreated mice, suggesting attenuated fibrosis. These findings raised the possibility of perhaps direct effects of MCH on myofibroblasts. Indeed, in biopsies from patients with IBD, we demonstrate expression of the MCH receptor MCHR1 in α-smooth muscle actin(+) subepithelial cells. CCD-18Co cells, a primary human colonic myofibroblast cell line, were also positive for MCHR1. In these cells, MCH acted as a profibrotic modulator by potentiating the effects of IGF-1 and TGF-β on proliferation and collagen production. Thus, by virtue of combined anti-inflammatory and anti-fibrotic effects, blocking MCH might represent a compelling approach for treating IBD.

  14. Alpha macroglobulins and the low-density-lipoprotein-related protein alpha-2-macroglobulin receptor in experimental renal fibrosis

    NARCIS (Netherlands)

    van Goor, H; Diamond, [No Value; Ding, GH; Kaysen, GA

    1999-01-01

    In this study, we evaluated the location of non-specific proteinase inhibitors and their receptor in experimental glomerular and interstitial fibrosis. The alpha macroglobulins alpha-2-macroglobulin (alpha 2M) and alpha-1-inhibitor 3 (alpha 1I3) are proteinase inhibitors, including

  15. The role of microRNA-155/liver X receptor pathway in experimental and idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Kurowska-Stolarska, Mariola; Hasoo, Manhl K; Welsh, David J; Stewart, Lynn; McIntyre, Donna; Morton, Brian E; Johnstone, Steven; Miller, Ashley M; Asquith, Darren L; Millar, Neal L; Millar, Ann B; Feghali-Bostwick, Carol A; Hirani, Nikhil; Crick, Peter J; Wang, Yuqin; Griffiths, William J; McInnes, Iain B; McSharry, Charles

    2017-06-01

    Idiopathic pulmonary fibrosis (IPF) is progressive and rapidly fatal. Improved understanding of pathogenesis is required to prosper novel therapeutics. Epigenetic changes contribute to IPF; therefore, microRNAs may reveal novel pathogenic pathways. We sought to determine the regulatory role of microRNA (miR)-155 in the profibrotic function of murine lung macrophages and fibroblasts, IPF lung fibroblasts, and its contribution to experimental pulmonary fibrosis. Bleomycin-induced lung fibrosis in wild-type and miR-155 -/- mice was analyzed by histology, collagen, and profibrotic gene expression. Mechanisms were identified by in silico and molecular approaches and validated in mouse lung fibroblasts and macrophages, and in IPF lung fibroblasts, using loss-and-gain of function assays, and in vivo using specific inhibitors. miR-155 -/- mice developed exacerbated lung fibrosis, increased collagen deposition, collagen 1 and 3 mRNA expression, TGF-β production, and activation of alternatively activated macrophages, contributed by deregulation of the miR-155 target gene the liver X receptor (LXR)α in lung fibroblasts and macrophages. Inhibition of LXRα in experimental lung fibrosis and in IPF lung fibroblasts reduced the exacerbated fibrotic response. Similarly, enforced expression of miR-155 reduced the profibrotic phenotype of IPF and miR-155 -/- fibroblasts. We describe herein a molecular pathway comprising miR-155 and its epigenetic LXRα target that when deregulated enables pathogenic pulmonary fibrosis. Manipulation of the miR-155/LXR pathway may have therapeutic potential for IPF. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Incidência de infecção em pacientes com cateter peridural tunelizado Incidencia de infección en pacientes con cateter peridural tunelizado Infection incidence in patients with tunneled peridural catheter

    Directory of Open Access Journals (Sweden)

    Maria Cecilia Iksilara

    2005-04-01

    Full Text Available O cateter peridural tunelizado como via de administração de opiáceos vem sendo utilizado desde o início de 1980. Pacientes com dor crônica, que não obtêm alívio com medicamentos por outras vias, são muito beneficiados com infusão de opiáceo associado a um anestésico local por via peridural. Entretanto, ainda existem dúvidas sobre a eficácia do método, no manuseio e, conseqüentemente, quanto ao risco de infecção e outras complicações. Sendo a equipe de enfermagem fundamental para efetivar o tratamento para o alívio da dor, esse estudo propõe demonstrar como manter a técnica segura. Foram acompanhados 27 pacientes com dor crônica entre 2002 e 2004, que utilizaram o cateter peridural por 18 dias em média, implantados em nível torácico ou lombar. Não houve complicações como abcesso peridural, meningite ou hematoma peridural. A satisfação dos pacientes quanto a analgesia foi evidente.El cateter peridural tunelizado, como via de administración de opióides, es utilizado desde el comienzo de 1980. Pacientes con dolor crónico, que no tienen alivio con medicamentos por otras vias, son muy beneficiados con la administración de opióides, asociados a un anestésico local por via peridural. Sin embargo, aún existen dudas sobre la eficacia del método, en el manejo y, como consecuencia, en el riesgo de infección y otras complicaciones. Siendo el equipo de enfermería fundamental para ejecutar el tratamiento para alivio del dolor, esto estudio se propone a presentar como mantener la técnica segura. Vinte y siete pacientes con dolor crónica, entre 2002 a 2004, que utilizarón el cateter peridural por 18 dias en media, fuerón seguidos. Los cateteres fuerón implantados al nivele toracico o lumbar. No se presentaran complicaciones como absceso peridural, meningitis o hematoma peridural. La satisfacción de los pacientes quanto analgesia fué evidente.The tunneled epidural catheter as an administration access for opiates

  17. Cateter peridural deslocado: uma causa de falha de analgesia. Relato de caso

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    Sudbrack Guilherme

    2002-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A migração do cateter peridural é uma ocorrência rara. No entanto, quando não se obtém bloqueio condutivo após injeção de anestésico local através do mesmo, deve-se suspeitar de que ele não esteja no local esperado. O objetivo deste relato é descrever um caso de migração de cateter peridural (L3-L4 para o interior do músculo psoas maior direito, confirmado radiologicamente. RELATO DO CASO: Paciente feminina com 58 anos, portadora de tromboangeíte obliterante foi submetida à amputação do hálux esquerdo sob técnica combinada raqui-peridural. A punção subaracnóidea foi feita em L4-L5 e o cateter peridural foi passado em L3-L4 com o objetivo de fazer analgesia controlada pelo paciente (ACP, por via peridural, no pós-operatório. Como a ACP não apresentou resultados no pós-operatório, suspeitou-se de migração do cateter peridural que foi confirmada por estudo radiográfico contrastado. O cateter saiu pelo forâmen intervertebral e ficou alojado no músculo psoas maior direito. CONCLUSÕES: A ausência de efeitos após injeções repetidas de soluções analgésicas através de cateter peridural faz suspeitar que o mesmo não esteja no local apropriado. Estudo radiológico com contraste pôde confirmar o diagnóstico.

  18. Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease

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    Mackness Michael

    2009-01-01

    Full Text Available Abstract Background Paraoxonase-1 (PON1 is an antioxidant enzyme synthesized by the liver. It protects against liver impairment and attenuates the production of the pro-inflammatory monocyte chemoattractant protein-1 (MCP-1. We investigated the relationships between hepatic PON1 and MCP-1 expression in rats with liver disease and explored the possible molecular mechanisms involved. Methods CCl4 was administered for up to 12 weeks to induce liver damage. Serum and hepatic levels of PON1 and MCP-1, their gene and protein expression, nuclear transcription factors, and histological and biochemical markers of liver impairment were measured. Results High levels of PON1 and MCP-1 expression were observed at 12th week in the hepatocytes surrounding the fibrous septa and inflammatory areas. CCl4-administered rats had an increased hepatic PON1 concentration that was related to decreased gene transcription and inhibited protein degradation. Decreased PON1 gene transcription was associated with PPARδ expression. These changes were accompanied by increased hepatic MCP-1 concentration and gene expression. There were significant direct relationships between hepatic PON1 and MCP-1 concentrations (P = 0.005 and between PON1 and the amount of activated stellate cells (P = 0.001. Conclusion Our results from this experimental model suggest a hepato-protective role for PON1 against inflammation, fibrosis and liver disease mediated by MCP-1.

  19. B cell activating factor is central to bleomycin- and IL-17-mediated experimental pulmonary fibrosis.

    Science.gov (United States)

    François, Antoine; Gombault, Aurélie; Villeret, Bérengère; Alsaleh, Ghada; Fanny, Manoussa; Gasse, Paméla; Adam, Sylvain Marchand; Crestani, Bruno; Sibilia, Jean; Schneider, Pascal; Bahram, Seiamak; Quesniaux, Valérie; Ryffel, Bernhard; Wachsmann, Dominique; Gottenberg, Jacques-Eric; Couillin, Isabelle

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive devastating, yet untreatable fibrotic disease of unknown origin. We investigated the contribution of the B-cell activating factor (BAFF), a TNF family member recently implicated in the regulation of pathogenic IL-17-producing cells in autoimmune diseases. The contribution of BAFF was assessed in a murine model of lung fibrosis induced by airway administered bleomycin. We show that murine BAFF levels were strongly increased in the bronchoalveolar space and lungs after bleomycin exposure. We identified Gr1(+) neutrophils as an important source of BAFF upon BLM-induced lung inflammation and fibrosis. Genetic ablation of BAFF or BAFF neutralization by a soluble receptor significantly attenuated pulmonary fibrosis and IL-1β levels. We further demonstrate that bleomycin-induced BAFF expression and lung fibrosis were IL-1β and IL-17A dependent. BAFF was required for rIL-17A-induced lung fibrosis and augmented IL-17A production by CD3(+) T cells from murine fibrotic lungs ex vivo. Finally we report elevated levels of BAFF in bronchoalveolar lavages from IPF patients. Our data therefore support a role for BAFF in the establishment of pulmonary fibrosis and a crosstalk between IL-1β, BAFF and IL-17A. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host-pathogen interactions in cystic fibrosis

    DEFF Research Database (Denmark)

    Moser, Claus; van Gennip, Maria; Bjarnsholt, Thomas

    2009-01-01

    Moser C, van Gennip M, Bjarnsholt T, Jensen PO, Lee B, Hougen HP, Calum H, Ciofu O, Givskov M, Molin S, Hoiby N. Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host-pathogen interactions in cystic fibrosis. APMIS 2009; 117: 95-107. The dominant cause of premature...... death in patients suffering from cystic fibrosis (CF) is chronic lung infection with Pseudomonas aeruginosa. The chronic lung infection often lasts for decades with just one clone. However, as a result of inflammation, antibiotic treatment and different niches in the lungs, the clone undergoes...... and 2003) of the chronic lung infection of one CF patient using the seaweed alginate embedment model. The results showed that the non-mucoid clones reduced their virulence over time, resulting in faster clearing of the bacteria from the lungs, improved pathology and reduced pulmonary production...

  1. Role of heat shock protein 47 in intestinal fibrosis of experimental colitis.

    Science.gov (United States)

    Kitamura, Hiroshi; Yamamoto, Shuji; Nakase, Hiroshi; Matsuura, Minoru; Honzawa, Yusuke; Matsumura, Kayoko; Takeda, Yasuhiro; Uza, Norimitsu; Nagata, Kazuhiro; Chiba, Tsutomu

    2011-01-14

    Intestinal fibrosis is a clinically important issue of inflammatory bowel disease (IBD). It is unclear whether or not heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, plays a critical role in intestinal fibrosis. The aim of this study is to investigate the role of HSP47 in intestinal fibrosis of murine colitis. HSP47 expression and localization were evaluated in interleukin-10 knockout (IL-10KO) and wild-type (WT, C57BL/6) mice by immunohistochemistry. Expression of HSP47 and transforming growth factor-β1 (TGF-β1) in colonic tissue was measured. In vitro studies were conducted in NIH/3T3 cells and primary culture of myofibroblasts separated from colonic tissue of IL-10KO (PMF KO) and WT mice (PMF WT) with stimulation of several cytokines. We evaluated the inhibitory effect of administration of small interfering RNA (siRNA) targeting HSP47 on intestinal fibrosis in IL-10KO mice in vivo. Immunohistochemistry revealed HSP47 positive cells were observed in the mesenchymal and submucosal area of both WT and IL-10 KO mice. Gene expressions of HSP47 and TGF-β1 were significantly higher in IL-10KO mice than in WT mice and correlated with the severity of inflammation. In vitro experiments with NIH3T3 cells, TGF-β1 only induced HSP47 gene expression. There was a significant difference of HSP47 gene expression between PMF KO and PMF WT. Administration of siRNA targeting HSP47 remarkably reduced collagen deposition in colonic tissue of IL-10KO mice. Our results indicate that HSP47 plays an essential role in intestinal fibrosis of IL-10KO mice, and may be a potential target for intestinal fibrosis associated with IBD. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. Role of IL-1β in experimental cystic fibrosis upon P. aeruginosa infection.

    Directory of Open Access Journals (Sweden)

    Jennifer Palomo

    Full Text Available Cystic fibrosis is associated with increased inflammatory responses to pathogen challenge. Here we revisited the role of IL-1β in lung pathology using the experimental F508del-CFTR murine model on C57BL/6 genetic background (Cftr(tm1eur or d/d, on double deficient for d/d and type 1 interleukin-1 receptor (d/d X IL-1R1-/-, and antibody neutralization. At steady state, young adult d/d mice did not show any signs of spontaneous lung inflammation. However, IL-1R1 deficiency conferred partial protection to repeated P. aeruginosa endotoxins/LPS lung instillation in d/d mice, as 50% of d/d mice succumbed to inflammation, whereas all d/d x IL-1R1-/- double mutants survived with lower initial weight loss and less pulmonary collagen and mucus production, suggesting that the absence of IL-1R1 signaling is protective in d/d mice in LPS-induced lung damage. Using P. aeruginosa acute lung infection we found heightened neutrophil recruitment in d/d mice with higher epithelial damage, increased bacterial load in BALF, and augmented IL-1β and TNF-α in parenchyma as compared to WT mice. Thus, F508del-CFTR mice show enhanced IL-1β signaling in response to P. aeruginosa. IL-1β antibody neutralization had no effect on lung homeostasis in either d/d or WT mice, however P. aeruginosa induced lung inflammation and bacterial load were diminished by IL-1β antibody neutralization. In conclusion, enhanced susceptibility to P. aeruginosa in d/d mice correlates with an excessive inflammation and with increased IL-1β production and reduced bacterial clearance. Further, we show that neutralization of IL-1β in d/d mice through the double mutation d/d x IL-1R1-/- and in WT via antibody neutralization attenuates inflammation. This supports the notion that intervention in the IL-1R1/IL-1β pathway may be detrimental in CF patients.

  3. A synthetic PPAR-γ agonist triterpenoid ameliorates experimental fibrosis: PPAR-γ-independent suppression of fibrotic responses.

    Science.gov (United States)

    Wei, Jun; Zhu, Hongyan; Komura, Kazuhiro; Lord, Gabriel; Tomcik, Michal; Wang, Wenxia; Doniparthi, Sruthi; Tamaki, Zenshiro; Hinchcliff, Monique; Distler, Joerg H W; Varga, John

    2014-02-01

    Persistent fibroblast activation initiated by transforming growth factor β (TGF-β) is a fundamental event in the pathogenesis of systemic sclerosis, and its pharmacological inhibition represents a potential therapeutic strategy. The nuclear receptor, peroxisome proliferator-activated receptor γ (PPAR-γ), exerts potent fibrotic activity. The synthetic oleanane triterpenoid, 2-cyano-3,12-dioxo-olean-1,9-dien-28-oic acid (CDDO), is a PPAR-γ agonist with potential effects on TGF-β signalling and dermal fibrosis. To examine the modulation of fibrogenesis by CDDO in explanted fibroblasts, skin organ cultures and murine models of scleroderma. The effects of CDDO on experimental fibrosis induced by bleomycin injection or by overexpression of constitutively active type I TGF-β receptor (TgfbR1ca) were evaluated. Modulation of fibrotic gene expression was examined in human skin organ cultures. To delineate the mechanisms underlying the antifibrotic effects of CDDO, explanted skin fibroblasts cultured in two-dimensional monolayers or in three-dimensional full-thickness human skin equivalents were studied. CDDO significantly ameliorated dermal fibrosis in two complementary mouse models of scleroderma, as well as in human skin organ cultures and in three-dimensional human skin equivalents. In two-dimensional monolayer cultures of explanted normal fibroblasts, CDDO abrogated fibrogenic responses induced by TGF-β. These CDDO effects occurred via disruption of Smad-dependent transcription and were associated with inhibition of Akt activation. In scleroderma fibroblasts, CDDO attenuated the elevated synthesis of collagen. Remarkably, the in vitro antifibrotic effects of CDDO were independent of PPAR-γ. The PPAR-γ agonist triterpenoid CDDO attenuates fibrogenesis by antagonistically targeting canonical TGF-β/Smad and Akt signalling in a PPAR-γ-independent manner. These findings identify this synthetic triterpenoid as a potential new therapy for the control of fibrosis.

  4. Senolytic drugs target?alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo

    OpenAIRE

    Lehmann, Mareike; Korfei, Martina; Mutze, Kathrin; Klee, Stephan; Skronska-Wasek, Wioletta; Alsafadi, Hani N.; Ota, Chiharu; Costa, Rita; Schiller, Herbert B.; Lindner, Michael; Wagner, Darcy E; G?nther, Andreas; K?nigshoff, Melanie

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor prognosis and limited therapeutic options. The incidence of IPF increases with age, and ageing-related mechanisms such as cellular senescence have been proposed as pathogenic drivers. The lung alveolar epithelium represents a major site of tissue injury in IPF and senescence of this cell population is probably detrimental to lung repair. However, the potential pathomechanisms of alveolar epithelial cell senescence and...

  5. Pan-PPAR agonist IVA337 is effective in experimental lung fibrosis and pulmonary hypertension.

    Science.gov (United States)

    Avouac, Jerome; Konstantinova, Irena; Guignabert, Christophe; Pezet, Sonia; Sadoine, Jeremy; Guilbert, Thomas; Cauvet, Anne; Tu, Ly; Luccarini, Jean-Michel; Junien, Jean-Louis; Broqua, Pierre; Allanore, Yannick

    2017-11-01

    To evaluate the antifibrotic effects of the pan-peroxisome proliferator-activated receptor (PPAR) agonist IVA337 in preclinical mouse models of pulmonary fibrosis and related pulmonary hypertension (PH). IVA337 has been evaluated in the mouse model of bleomycin-induced pulmonary fibrosis and in Fra-2 transgenic mice, this latter being characterised by non-specific interstitial pneumonia and severe vascular remodelling of pulmonary arteries leading to PH. Mice received two doses of IVA337 (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks. IVA337 demonstrated at a dose of 100 mg/kg a marked protection from the development of lung fibrosis in both mouse models compared with mice receiving 30 mg/kg of IVA337 or vehicle. Histological score was markedly reduced by 61% in the bleomycin model and by 50% in Fra-2 transgenic mice, and total lung hydroxyproline concentrations decreased by 28% and 48%, respectively, as compared with vehicle-treated mice. IVA337 at 100 mg/kg also significantly decreased levels of fibrogenic markers in lesional lungs of both mouse models. In addition, IVA337 substantially alleviated PH in Fra-2 transgenic mice by improving haemodynamic measurements and vascular remodelling. In primary human lung fibroblasts, IVA337 inhibited in a dose-dependent manner fibroblast to myofibroblasts transition induced by TGF-β and fibroblast proliferation mediated by PDGF. We demonstrate that treatment with 100 mg/kg IVA337 prevents lung fibrosis in two complementary animal models and substantially attenuates PH in the Fra-2 mouse model. These findings confirm that the pan-PPAR agonist IVA337 is an appealing therapeutic candidate for these cardiopulmonary involvements. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. In situ forming hydrogel composed of hyaluronate and polygalacturonic acid for prevention of peridural fibrosis.

    Science.gov (United States)

    Lin, Cheng-Yi; Peng, Hsiu-Hui; Chen, Mei-Hsiu; Sun, Jui-Sheng; Liu, Tse-Ying; Chen, Ming-Hong

    2015-04-01

    Hyaluronic acid-based hydrogels can reduce postoperative adhesion. However, the long-term application of hyaluronic acid is limited by tissue mediated enzymatic degradation. To overcome this limitation, we developed a polygalacturonic acid and hyaluronate composite hydrogel by Schiff's base crosslinking reaction. The polygalacturonic acid and hyaluronate composite hydrogels had short gelation time (less than 15 s) and degraded by less than 50 % in the presence of hyaluronidase for 7 days. Cell adhesion and migration assays showed polygalacturonic acid and hyaluronate composite hydrogels prevented fibroblasts from adhesion and infiltration into the hydrogels. Compared to hyaluronate hydrogels and commercial Medishield™ gels, polygalacturonic acid and hyaluronate composite hydrogel was not totally degraded in vivo after 4 weeks. In the rat laminectomy model, polygalacturonic acid and hyaluronate composite hydrogel also had better adhesion grade and smaller mean area of fibrous tissue formation over the saline control and hyaluronate hydrogel groups. Polygalacturonic acid and hyaluronate composite hydrogel is a system that can be easy to use due to its in situ cross-linkable property and potentially promising for adhesion prevention in spine surgeries.

  7. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice.

    Science.gov (United States)

    Mridha, Auvro R; Wree, Alexander; Robertson, Avril A B; Yeh, Matthew M; Johnson, Casey D; Van Rooyen, Derrick M; Haczeyni, Fahrettin; Teoh, Narci C-H; Savard, Christopher; Ioannou, George N; Masters, Seth L; Schroder, Kate; Cooper, Matthew A; Feldstein, Ariel E; Farrell, Geoffrey C

    2017-05-01

    NOD-like receptor protein 3 (NLRP3) inflammasome activation occurs in Non-alcoholic fatty liver disease (NAFLD). We used the first small molecule NLRP3 inhibitor, MCC950, to test whether inflammasome blockade alters inflammatory recruitment and liver fibrosis in two murine models of steatohepatitis. We fed foz/foz and wild-type mice an atherogenic diet for 16weeks, gavaged MCC950 or vehicle until 24weeks, then determined NAFLD phenotype. In mice fed an methionine/choline deficient (MCD) diet, we gavaged MCC950 or vehicle for 6weeks and determined the effects on liver fibrosis. In vehicle-treated foz/foz mice, hepatic expression of NLRP3, pro-IL-1β, active caspase-1 and IL-1β increased at 24weeks, in association with cholesterol crystal formation and NASH pathology; plasma IL-1β, IL-6, MCP-1, ALT/AST all increased. MCC950 treatment normalized hepatic caspase 1 and IL-1β expression, plasma IL-1β, MCP-1 and IL-6, lowered ALT/AST, and reduced the severity of liver inflammation including designation as NASH pathology, and liver fibrosis. In vitro, cholesterol crystals activated Kupffer cells and macrophages to release IL-1β; MCC950 abolished this, and the associated neutrophil migration. MCD diet-fed mice developed fibrotic steatohepatitis; MCC950 suppressed the increase in hepatic caspase 1 and IL-1β, lowered numbers of macrophages and neutrophils in the liver, and improved liver fibrosis. MCC950, an NLRP3 selective inhibitor, improved NAFLD pathology and fibrosis in obese diabetic mice. This is potentially attributable to the blockade of cholesterol crystal-mediated NLRP3 activation in myeloid cells. MCC950 reduced liver fibrosis in MCD-fed mice. Targeting NLRP3 is a logical direction in pharmacotherapy of NASH. Fatty liver disease caused by being overweight with diabetes and a high risk of heart attack, termed non-alcoholic steatohepatitis (NASH), is the most common serious liver disease with no current treatment. There could be several causes of inflammation

  8. Histochemical and cellular changes accompanying the appearance of lung fibrosis in an experimental mouse model for Hermansky Pudlak syndrome

    Science.gov (United States)

    Lyerla, Timothy

    2010-01-01

    Hermansky Pudlak syndrome (HPS) is a heterogeneous recessive genetic disease with a tendency to develop lung fibrosis with aging. A mouse strain with two mutant HPS genes affecting separate vesicle trafficking pathways, C57BL/6-Hps1ep-Ap3b1pe, exhibits severe lung abnormalities at young ages, including enlarged alveolar type II (ATII) cells with giant lamellar bodies and foamy alveolar macrophages (AMs), which are readily identified histologically. In this study, the appearance of lung fibrosis in older animals was studied using classical histological and biochemical methods. The HPS double mutant mice, but not Chediak Higashi syndrome (C57BL/6-Lystbg-J-J, CHS) or C57BL/6J black control (WT) mice, were found to develop lung fibrosis at about 17 months of age using Masson trichrome staining, which was confirmed by hydroxyproline analysis. TGF β1 levels were elevated in bronchial alveolar lavage samples at all ages tested in the double mutant, but not WT or CHS mice, indicative of a prefibrotic condition in this experimental strain; and AMs were highly positive for this cytokine using immunohistochemistry staining. Prosurfactant protein C staining for ATII cells showed redistribution and dysmorphism of these cells with aging, but there was no evidence for epithelial-mesenchymal transition of ATII cells by dual staining for prosurfactant C protein and α-smooth muscle actin. This investigation showed that the HPS double mutant mouse strain develops interstitial pneumonia (HPSIP) past 1 year of age, which may be initiated by abnormal ATII cells and exacerbated by AM activation. With prominent prefibrotic abnormalities, this double mutant may serve as a model for interventive therapy in HPS. PMID:20603711

  9. Dexmedetomidina via endovenosa vs. clorhidrato de morfina y nalbufina via peridural: alternativas de analgesia perioperatoria en perras sometidas a ovariohisterectomia electiva

    National Research Council Canada - National Science Library

    Chavez-Oberto, Victor; Villarroel, Fernando; Polanco, Rito; Villarroel, Rommer; Nunez, Jorge

    2014-01-01

    .... El objetivo de la investigacion fue evaluar el efecto analgesico de dexmedetomidina endovenosa, clorhidrato de morfina y nalbufina via peridural en perras sometidas a ovariohisterectomia electiva...

  10. Uso de vitamina C en la solución tumescente de liposucción como inductor de lipolisis y fibrosis: Trabajo experimental Use of vitamine C in liposuction tumescent solution as lipolisis and fibrosis inductor: Experimental study

    Directory of Open Access Journals (Sweden)

    N. Antoniadis Petrakis

    2007-06-01

    Full Text Available La Liposucción no permite siempre extraer todo el tejido adiposo causante de la lipodistrofia, por lo cual se plantea la necesidad de perfeccionar esta técnica. Nuestro objetivo es el demostrar que el uso de la vitamina C en la solución tumescente induce lipólisis y aumenta la fibrosis. El presente es un estudio descriptivo, prospectivo, experimental y comparativo de una muestra de 30 ratas Sprague-Dawley de ambos sexos, a las cuales se les infiltró solución tumescente en el tejido subdérmico de la región inguinal, con vitamina C al grupo experimental y con solución tumescente sin vitamina C al grupo control, para su posterior estudio histológico macroscópico y microscópico. El 100% de las muestras con vitamina C evidenciaron cambios a nivel del tejido adiposo sugerentes de lipólisis y en el 82% se evidenciaron cambios en el tejido conectivo sugerentes de formación de colágeno joven. Concluimos que la vitamina C favorece la lipolisis y promueve la síntesis de colágeno cuando se utiliza como parte de la solución tumescente en animales de experimentaciónLiposuction does not always let to remove all the amount of adipose tissue which causes lipodistrophy, for that reason, it is recommended the necessity to improve that technique. We try to demonstrate that the use of vitamin C in the tumescence solution induces lipolysis and raises fibrosis. This article is a descriptive, prospective, experimental and comparative research of a sample of 30 mice of Sprague- Dawley type of both sexes, which were infiltrated with a tumescence solution in the subdermic inguinal region with vitamin C to the experimental group and with tumescence solution without vitamin C to the control group, for a further histological macroscopic as well as microscopic study. The results showed that 100% of the samples with vitamin C presented changes in the adipose tissue which suggested lipolysis, whereas 82% were evidence for the formation of young collagen. As a

  11. Dor neuropática após trauma com agulha de peridural

    Directory of Open Access Journals (Sweden)

    Gilson Cassem Ramos

    2008-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Complicações neurológicas decorrentes de anestesia peridural são incomuns. O trauma mecânico direto em raízes nervosas pode provocar dor neuropática que costuma evoluir de maneira favorável; contudo, trata-se de complicação potencialmente grave que, em certas circunstâncias, pode progredir para quadro crônico. O objetivo foi discorrer o tema dor neuropática aguda e traumática, abordando, sobretudo, sobre o seu tratamento. RELATO DO CASO: Paciente do sexo masculino, admitido para tratamento cirúrgico de refluxo gastroesofágico, pela técnica laparoscópica e com alta hospitalar prevista para o primeiro pós-operatório (PO. Submeteu-se a bloqueio anestésico peridural associado à anestesia geral. Durante a localização do espaço peridural, o paciente referiu dor muito intensa e parestesia em membro inferior esquerdo. A agulha foi reposicionada e o espaço peridural localizado. O paciente evoluiu no PO com alodinia e hiperestesia. Foi firmado o diagnóstico de dor neuropática. O tratamento instituído constou de antidepressivo, anticonvulsivante, corticóide, tramadol e complexo vitamínico B. No 28º PO o paciente apresentava-se assintomático e com exame físico normal, quando recebeu alta médica. CONCLUSÕES: A evolução do quadro com o tratamento proposto foi favorável. O diagnóstico e tratamento precoces podem evitar lesões irreversíveis, mudar o prognóstico dos pacientes e evitar desdobramentos de caráter social e médico-legal.

  12. Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Parra, E.R.; Pincelli, M.S. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Teodoro, W.R.; Velosa, A.P.P. [Disciplina de Reumatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Martins, V.; Rangel, M.P.; Barbas-Filho, J.V.; Capelozzi, V.L. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-06-04

    Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis.

  13. Pneumoencéfalo após anestesia peridural: relato de caso

    Directory of Open Access Journals (Sweden)

    Angélica de Fátima de Assunção Braga

    2001-01-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O bloqueio peridural constitui técnica utilizada para alívio da dor durante o trabalho de parto. Apesar das vantagens, não é isenta de complicações, como, por exemplo, o pneumoencéfalo. O objetivo deste relato é apresentar um caso de pneumoencéfalo iatrogênico, diagnosticado após bloqueio peridural, com punção acidental de duramáter. RELATO DO CASO: Paciente de 16 anos, estado físico ASA I, sem antecedentes anestésicos, submetida a bloqueio peridural contínuo para analgesia de parto. Após várias tentativas de punções no espaço L3-L4, ocorreu punção acidental de duramáter. Optou-se por nova punção peridural em L2-L3, sem sucesso. Foi tentada outra punção em L3-L4, e após identificação do espaço peridural empregando-se a técnica da perda da resistência com ar, injetou-se o anestésico local e fentanil, seguido de passagem do cateter. Após 20 minutos da instalação do bloqueio, ocorreu sofrimento fetal, com indicação de cesariana, sendo administrada dose complementar de anestésico local pelo cateter. A paciente permaneceu hemodinamicamente estável e consciente durante a cirurgia, com lenta recuperação do bloqueio motor (14 h. No pós-operatório, apresentou dois episódios de crise convulsiva, com intervalo de 12 horas entre eles, que reverteram espontaneamente. A avaliação neurológica era normal e a tomografia computadorizada revelou imagem com densidade de ar compatível com pneumoencéfalo. A paciente teve alta três dias após, sem seqüelas. CONCLUSÕES: O caso confirma a possibilidade de se causar pneumoencéfalo iatrogênico durante a realização de bloqueio peridural, empregando-se a técnica da perda de resistência ao ar para a identificação do espaço peridural. Na presença de sinais e sintomas de irritação meníngea, a tomografia computadorizada é o meio diagnóstico recomendado para o diagnóstico diferencial entre pneumoencéfalo e as demais causas.

  14. Incidência de tremor em anestesia peridural com ou sem fentanil: estudo comparativo

    Directory of Open Access Journals (Sweden)

    Abreu Múcio Paranhos de

    2004-01-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A maioria dos trabalhos encontrados na literatura, relacionando a influência dos opióides administrados por via peridural com o tremor intra e pós-operatório, foram realizados com grupos de pacientes obstétricas, nas quais a resposta do centro termorregulador pode ser diferente das pacientes não grávidas. O objetivo deste trabalho foi comparar o bloqueio peridural com e sem fentanil, quanto à incidência de tremores e outras complicações no intra e pós-operatório em pacientes submetidos à cirurgia de varizes sob anestesia peridural com bupivacaína a 0,5% com adrenalina a 1:200.000. MÉTODO: Trinta e quatro pacientes, estado físico ASA I e II, submetidos à cirurgia para tratamento de varizes de membros inferiores, foram divididos aleatoriamente em 2 grupos (n = 17, e receberam midazolam (0,05 mg.kg-1, por via venosa seguido de anestesia peridural lombar, utilizando-se no grupo S, 20 ml bupivacaína a 0,5% (com vasoconstritor associado a 2 ml de solução fisiológica a 0,9% e no grupo F, 20 ml de bupivacaína a 0,5% (com vasoconstritor associada ao fentanil (100 µg. Foram estudados: incidência de tremor, temperatura dos pacientes, necessidade do uso de meperidina, e a incidência de náuseas e vômitos nos seguintes momentos: M1 - admissão do paciente na sala de operação; M2 - imediatamente antes da anestesia; M3 - 30 minutos após o término da injeção do anestésico local; M4 - 60 minutos após o término da injeção do anestésico local; M5 - 90 minutos após o término da injeção do anestésico local; M6 - final da anestesia; M7 - antecedendo a alta da sala de recuperação pós-anestésica. RESULTADOS: Quanto aos dados antropométricos, estado físico, tempo médio de duração da anestesia e cirurgia, temperatura dos pacientes e da sala de operação e incidência de náuseas e vômitos não houve diferença estatística entre os grupos. Houve diferença estatística aos 60 minutos (M4 e

  15. S-nitroso-N-acetylcysteine attenuates liver fibrosis in experimental nonalcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Mazo DF

    2013-06-01

    Full Text Available Daniel FC Mazo,1 Marcelo G de Oliveira,2 Isabel VA Pereira,1 Bruno Cogliati,3 José T Stefano,1 Gabriela FP de Souza,2 Fabíola Rabelo,1 Fabiana R Lima,4 Venâncio A Ferreira Alves,4 Flair J Carrilho,1 Claudia PMS de Oliveira1 1University of São Paulo School of Medicine, Department of Gastroenterology, Clinical Division, Hepatology Branch (LIM-07, Sao Paulo, Brazil; 2Institute of Chemistry, University of Campinas, Campinas, Sao Paulo, Brazil; 3University of Sao Paulo School of Veterinary Medicine and Animal Science, Department of Pathology, Sao Paulo, Brazil; 4University of São Paulo School of Medicine, Department of Pathology (LIM14, São Paulo, Brazil Abstract: S-Nitroso-N-acetylcysteine (SNAC is a water soluble primary S-nitrosothiol capable of transferring and releasing nitric oxide and inducing several biochemical activities, including modulation of hepatic stellate cell activation. In this study, we evaluated the antifibrotic activity of SNAC in an animal model of nonalcoholic steatohepatitis (NASH induced in Sprague-Dawley rats fed with a choline-deficient, high trans fat diet and exposed to diethylnitrosamine for 8 weeks. The rats were divided into three groups: SNAC, which received oral SNAC solution daily; NASH, which received the vehicle; and control, which received standard diet and vehicle. Genes related to fibrosis (matrix metalloproteinases [MMP]-13, -9, and -2, transforming growth factor ß-1 [TGFß-1], collagen-1a, and tissue inhibitors of metalloproteinase [TIMP-1 and -2] and oxidative stress (heat-shock proteins [HSP]-60 and -90 were evaluated. SNAC led to a 34.4% reduction in the collagen occupied area associated with upregulation of MMP-13 and -9 and downregulation of HSP-60, TIMP-2, TGFß-1, and collagen-1α. These results indicate that oral SNAC administration may represent a potential antifibrotic treatment for NASH. Keywords: nitric oxide, S-nitroso-N-acetylcysteine, fibrogenesis, NASH, diethylnitrosamine

  16. Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid

    Directory of Open Access Journals (Sweden)

    Li Chun-jun

    2012-06-01

    Full Text Available Abstract Background Alpha-lipoic acid (ALA, a naturally occurring compound, exerts powerful protective effects in various cardiovascular disease models. However, its role in protecting against diabetic cardiomyopathy (DCM has not been elucidated. In this study, we have investigated the effects of ALA on cardiac dysfunction, mitochondrial oxidative stress (MOS, extracellular matrix (ECM remodeling and interrelated signaling pathways in a diabetic rat model. Methods Diabetes was induced in rats by I.V. injection of streptozotocin (STZ at 45 mg/kg. The animals were randomly divided into 4 groups: normal groups with or without ALA treatment, and diabetes groups with or without ALA treatment. All studies were carried out 11 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate cardiac function. Mitochondrial oxidative biochemical parameters were measured by spectophotometeric assays. Extracellular matrix content (total collagen, type I and III collagen was assessed by staining with Sirius Red. Gelatinolytic activity of Pro- and active matrix metalloproteinase-2 (MMP-2 levels were analyzed by a zymogram. Cardiac fibroblasts differentiation to myofibroblasts was evaluated by Western blot measuring smooth muscle actin (α-SMA and transforming growth factor–β (TGF-β. Key components of underlying signaling pathways including the phosphorylation of c-Jun N-terminal kinase (JNK, p38 MAPK and ERK were also assayed by Western blot. Results DCM was successfully induced by the injection of STZ as evidenced by abnormal heart mass and cardiac function, as well as the imbalance of ECM homeostasis. After administration of ALA, left ventricular dysfunction greatly improved; interstitial fibrosis also notably ameliorated indicated by decreased collagen deposition, ECM synthesis as well as enhanced ECM degradation. To further assess the underlying mechanism of improved DCM by ALA, redox status and cardiac remodeling associated

  17. A comparative study on the hepatoprotective action of bear bile and coptidis rhizoma aqueous extract on experimental liver fibrosis in rats

    Directory of Open Access Journals (Sweden)

    Wang Ning

    2012-11-01

    Full Text Available Abstract Aim of the study Bear bile and Coptidis Rhizoma have been used in Chinese medicine with a long tradition in treating heat-diseases. Both bear bile and Coptidis Rhizoma are used to treat liver diseases in clinical practice of Chinese Medicine. Since bears are currently endangered, it raises the question whether the use of bear bile is ethical. To look for substitute for bear bile, the aim of this study is to compare the anti-fibrotic effects of Coptidis Rhizoma and its major component berberine with the actions of bear bile and its major compound tauroursodeoxycholic acid on experimental liver fibrosis in rats. Method Quality assessment was conducted with high performance liquid chromatography. The experimental liver fibrosis in rats was induced by carbon tetrachloride, alcohol, and bile duct ligation respectively. The biochemical criteria in the blood and tissue samples were measured to evaluate the anti-fibrotic properties and underlying mechanisms of the drugs. Results Coptidis Rhizoma Aqueous Extract (CRAE, berberine, and bear bile exerted anti-fibrotic properties on various liver fibrosis models in rats. CRAE and berberine significantly reduced the peroxidative stress in liver through increasing the superoxide dismutase enzyme activity. CRAE and berberine were able to excrete bilirubin products from the liver and protect hepatocytes from cholestatic damage. The effect of CRAE and berberine are comparable to that of bear bile. Conclusion Instead of using bear bile, CRAE and berberine can be potential substitutes in treating liver fibrosis.

  18. A comparative study on the hepatoprotective action of bear bile and Coptidis Rhizoma aqueous extract on experimental liver fibrosis in rats.

    Science.gov (United States)

    Wang, Ning; Feng, Yibin; Cheung, Fan; Chow, Oi-Yee; Wang, Xuanbin; Su, Weiwei; Tong, Yao

    2012-11-29

    Bear bile and Coptidis Rhizoma have been used in Chinese medicine with a long tradition in treating heat-diseases. Both bear bile and Coptidis Rhizoma are used to treat liver diseases in clinical practice of Chinese Medicine. Since bears are currently endangered, it raises the question whether the use of bear bile is ethical. To look for substitute for bear bile, the aim of this study is to compare the anti-fibrotic effects of Coptidis Rhizoma and its major component berberine with the actions of bear bile and its major compound tauroursodeoxycholic acid on experimental liver fibrosis in rats. Quality assessment was conducted with high performance liquid chromatography. The experimental liver fibrosis in rats was induced by carbon tetrachloride, alcohol, and bile duct ligation respectively. The biochemical criteria in the blood and tissue samples were measured to evaluate the anti-fibrotic properties and underlying mechanisms of the drugs. Coptidis Rhizoma Aqueous Extract (CRAE), berberine, and bear bile exerted anti-fibrotic properties on various liver fibrosis models in rats. CRAE and berberine significantly reduced the peroxidative stress in liver through increasing the superoxide dismutase enzyme activity. CRAE and berberine were able to excrete bilirubin products from the liver and protect hepatocytes from cholestatic damage. The effect of CRAE and berberine are comparable to that of bear bile. Instead of using bear bile, CRAE and berberine can be potential substitutes in treating liver fibrosis.

  19. Nova técnica de cateterização de uso prolongado em canal peridural sacral de coelhos

    Directory of Open Access Journals (Sweden)

    Yüksel Erkin

    2013-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O objetivo deste estudo foi desenvolver uma técnica simples e prática para a cateterização crônica em canal peridural sacral de coelhos. MÉTODOS: O estudo incluiu dez coelhos com peso entre 2 e 2,5 kg. Após a anestesia e a analgesia, colocamos um cateter peridural através de uma incisão longitudinal de 2 cm na cauda acima da região do hiato sacral. Confirmamos a localização com a administração de lidocaína a 1% (nivelamento da perda sensorial e da função motora dos membros inferiores. O cateter foi introduzido através de um túnel subcutâneo até o pescoço, onde foi fixado. RESULTADOS: A implantação de cateter crônico peridural caudal foi bem-sucedida em todos os coelhos. Os cateteres permaneceram eficazmente no lugar por dez dias, sem intercorrências durante esse período. A localização do cateter foi reconfirmada por lidocaína a 1% no último dia. Após matar os animais, procedeu-se laminectomia para localização do cateter no espaço peridural. CONCLUSÕES: Há vários métodos de cateterização do espaço peridural em modelos animais na literatura. A cateterização do espaço peridural em coelhos pode ser feita através das vias atlanto-occipital, lombar ou caudal por amputação da cauda. As técnicas de cateterização intratecal e peridural descritas na literatura exigem perícia cirúrgica e conhecimento de procedimentos cirúrgicos, como laminectomia e amputação da cauda. A nossa técnica não requer grande habilidade cirúrgica, a integridade anatômica foi preservada e não houve mau posicionamento de cateter. Em conclusão, podemos sugerir que a nova técnica de cateterização peridural é simples, facilmente aplicável e pode ser usada em estudos experimentais de modelos animais.

  20. Lidocaína com vasoconstrictor isolada e associada ao fentanil via peridural em cães

    OpenAIRE

    Cassu,Renata Navarro; Melchert,Alessandra; Silva,Ana Paula Gasparotto da; Reis,Atilana Maniezo dos; Meirelles,Carlos Collares

    2010-01-01

    O objetivo deste estudo cego foi avaliar os efeitos cardiorrespiratórios e analgésicos de diferentes doses de fentanil associado à lidocaína com vasoconstrictor via peridural em cães. Foram avaliados 28 cães adultos, distribuídos em quatro tratamentos: 5mg kg-1 de lidocaína isolada (L) e associada ao fentanil nas doses de 2,5, 5 e 7mg kg-1 (F2,5, F5 e F7, respectivamente). Quinze minutos antes da punção peridural, todos os animais foram tranquilizados por via intravenosa (IV) com acepromazina...

  1. Experimental liver fibrosis induced in rats receiving high doses of alcohol and alternating between regular and vitamin-depleted diets.

    Science.gov (United States)

    Hirano, H; Hirano, T; Hirata, K; Tamura, M; Yamaura, T; Hamada, T

    1996-07-15

    Liver fibrosis was induced in rats by simulating human alcoholic eating and drinking patterns. Alcohol addiction was established by gradually increasing the ethanol concentration in the drinking water; salts were added at the terminal stage. The hepatocytes of rats receiving alcohol concentrations exceeding 50% (v/v) (similar to vodka) exhibited alcoholic hyaline (Mallory bodies). Alcoholic liver fibrosis was induced by alternating between regular and autoclaved (vitamin-depleted) diets, simulating the irregular eating habits of human alcoholics. In the livers of rats receiving 70% (v/v) ethanol (comparable to absinthe) with 25% saline and fed the alternating diets, pericellular fibrosis was induced. No significant difference in calorie intake between control and alcohol rats was detected except when rats underwent drinking bouts (heavy drinking phase). This indicates that neither a high-fat diet nor a choline-depleted diet is necessary to induce the alcoholic fibrosis seen in human alcoholics.

  2. Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis.

    Science.gov (United States)

    Wollin, Lutz; Maillet, Isabelle; Quesniaux, Valérie; Holweg, Alexander; Ryffel, Bernhard

    2014-05-01

    The tyrosine kinase inhibitor nintedanib (BIBF 1120) is in clinical development for the treatment of idiopathic pulmonary fibrosis. To explore its mode of action, nintedanib was tested in human lung fibroblasts and mouse models of lung fibrosis. Human lung fibroblasts expressing platelet-derived growth factor (PDGF) receptor-α and -β were stimulated with platelet-derived growth factor BB (homodimer) (PDGF-BB). Receptor activation was assessed by autophosphorylation and cell proliferation by bromodeoxyuridine incorporation. Transforming growth factor β (TGFβ)-induced fibroblast to myofibroblast transformation was determined by α-smooth muscle actin (αSMA) mRNA analysis. Lung fibrosis was induced in mice by intratracheal bleomycin or silica particle administration. Nintedanib was administered every day by gavage at 30, 60, or 100 mg/kg. Preventive nintedanib treatment regimen started on the day that bleomycin was administered. Therapeutic treatment regimen started at various times after the induction of lung fibrosis. Bleomycin caused increased macrophages and lymphocytes in the bronchoalveolar lavage (BAL) and elevated interleukin-1β (IL-1β), tissue inhibitor of metalloproteinase-1 (TIMP-1), and collagen in lung tissue. Histology revealed chronic inflammation and fibrosis. Silica-induced lung pathology additionally showed elevated BAL neutrophils, keratinocyte chemoattractant (KC) levels, and granuloma formation. Nintedanib inhibited PDGF receptor activation, fibroblast proliferation, and fibroblast to myofibroblast transformation. Nintedanib significantly reduced BAL lymphocytes and neutrophils but not macrophages. Furthermore, interleukin-1β, KC, TIMP-1, and lung collagen were significantly reduced. Histologic analysis showed significantly diminished lung inflammation, granuloma formation, and fibrosis. The therapeutic effect was dependent on treatment start and duration. Nintedanib inhibited receptor tyrosine kinase activation and the proliferation and

  3. Treatment of Intestinal Fibrosis in Experimental Inflammatory Bowel Disease by the Pleiotropic Actions of a Local Rho Kinase Inhibitor.

    Science.gov (United States)

    Holvoet, Tom; Devriese, Sarah; Castermans, Karolien; Boland, Sandro; Leysen, Dirk; Vandewynckel, Yves-Paul; Devisscher, Lindsey; Van den Bossche, Lien; Van Welden, Sophie; Dullaers, Melissa; Vandenbroucke, Roosmarijn E; De Rycke, Riet; Geboes, Karel; Bourin, Arnaud; Defert, Olivier; Hindryckx, Pieter; De Vos, Martine; Laukens, Debby

    2017-10-01

    Intestinal fibrosis resulting in (sub)obstruction is a common complication of Crohn's disease (CD). Rho kinases (ROCKs) play multiple roles in TGFβ-induced myofibroblast activation that could be therapeutic targets. Because systemic ROCK inhibition causes cardiovascular side effects, we evaluated the effects of a locally acting ROCK inhibitor (AMA0825) on intestinal fibrosis. Fibrosis was assessed in mouse models using dextran sulfate sodium (DSS) and adoptive T-cell transfer. The in vitro and ex vivo effects of AMA0825 were studied in different cell types and in CD biopsy cultures. ROCK is expressed in fibroblastic, epithelial, endothelial, and muscle cells of the human intestinal tract and is activated in inflamed and fibrotic tissue. Prophylactic treatment with AMA0825 inhibited myofibroblast accumulation, expression of pro-fibrotic factors, and accumulation of fibrotic tissue without affecting clinical disease activity and histologic inflammation in 2 models of fibrosis. ROCK inhibition reversed established fibrosis in a chronic DSS model and impeded ex vivo pro-fibrotic protein secretion from stenotic CD biopsies. AMA0825 reduced TGFβ1-induced activation of myocardin-related transcription factor (MRTF) and p38 mitogen-activated protein kinase (MAPK), down-regulating matrix metalloproteinases, collagen, and IL6 secretion from fibroblasts. In these cells, ROCK inhibition potentiated autophagy, which was required for the observed reduction in collagen and IL6 production. AMA0825 did not affect pro-inflammatory cytokine secretion from other ROCK-positive cell types, corroborating the selective in vivo effect on fibrosis. Local ROCK inhibition prevents and reverses intestinal fibrosis by diminishing MRTF and p38 MAPK activation and increasing autophagy in fibroblasts. Overall, our results show that local ROCK inhibition is promising for counteracting fibrosis as an add-on therapy for CD. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights

  4. Collagen crosslink location: a molecular marker for fibrosis in lungs of rats with experimental silicosis

    Energy Technology Data Exchange (ETDEWEB)

    Gerriets, J.E.; Reiser, K.M.; Last, J.A.

    1986-05-01

    Collagen content is increased in lungs of animals with experimental silicosis. They hypothesize that the collagen deposited in such fibrotic lungs differs structurally from normal lung collagen. Silicotic lung collagen shows an increase in lysine hydroxylation. In addition, the ratio of the difunctional crosslinks DHLNL (dihydroxylysinonorleucine) to HLNL (hydroxylysinonorleucine) is sharply elevated compared to that in control lungs. The peptide ..cap alpha..1(I)CB7 x ..cap alpha..2(I)CB1 crosslinked by HLNL was demonstrated in NaB/sup 3/H/sub 4/-reduced, CNBr-digested collagen from rat tail tendon by peptide purification, followed by periodate oxidation and amino acid analysis. Further structural analysis of this peptide was obtained by digestion of the crosslinked peptide with trypsin and purification of the tryptic peptide containing this crosslink followed by amino acid analysis. They then examined the analogous collagenous peptide in normal and silicotic lungs and analyzed the crosslink it contained. They observed that DHLNL was present at specific sites previously containing HLNL; that is, the collagen in fibrotic lungs is altered at specific sites by post-translational modification of a lysine residue by hydroxylation in a predictable way. They conclude that such unusual hydroxylation of a specific lysine residue in the ..cap alpha..2 chain provides a molecular marker for fibrotic lung collagen.

  5. Caffeine prevents experimental liver fibrosis by blocking the expression of TGF-β.

    Science.gov (United States)

    Arauz, Jonathan; Zarco, Natanael; Segovia, José; Shibayama, Mineko; Tsutsumi, Victor; Muriel, Pablo

    2014-02-01

    There is a growing body of evidence that caffeine exerts beneficial effects on the liver; however, the molecular mechanisms by which caffeine exerts beneficial effects on the liver are poorly defined. The aim of the present study was to examine the efficacy of caffeine in preventing thioacetamide (TAA)-induced cirrhosis in rats. Cirrhosis was induced by chronic TAA administration and the effects of coadministration of caffeine for 8 weeks were evaluated, including control groups. The administration of TAA induced liver cirrhosis, which was inhibited by caffeine. Caffeine prevents elevation of liver enzymes. Liver histopathology and hydroxyproline levels were significantly lower in the rats treated with TAA plus caffeine compared with TAA only. Caffeine shows antioxidant properties by restoring the redox equilibrium [lipid peroxidation and glutathione peroxidase (GPx) levels]. Western blot assays showed blockade of the expression of transforming growth factor-β and its downstream inductor connective tissue growth factor. Similarly, caffeine decreases messenger RNA levels of these profibrogenic proteins. In addition, caffeine inhibits hepatic stellate cells because of blockade of the expression of α-smooth muscle actin; in the western blot assay, we also found low levels of mRNA of collagen α1. Zymography assays showed that caffeine had an effect on the activity of matrix metalloproteinases 2 and 9, but no effect on the expression of tissue inhibitor of metalloproteinases-1, using RT-PCR. Our results show that caffeine prevents experimental cirrhosis; the mechanisms of action are associated with its antioxidant properties and mainly by its ability to block the elevation of the profibrogenic cytokine transforming growth factor-β, which may be associated with attenuation of the inflammatory and fibrotic processes.

  6. Pulmonary Fibrosis

    Science.gov (United States)

    Pulmonary fibrosis is a condition in which the tissue deep in your lungs becomes scarred over time. This ... blood may not get enough oxygen. Causes of pulmonary fibrosis include environmental pollutants, some medicines, some connective tissue ...

  7. Naringenin prevents experimental liver fibrosis by blocking TGFβ-Smad3 and JNK-Smad3 pathways.

    Science.gov (United States)

    Hernández-Aquino, Erika; Zarco, Natanael; Casas-Grajales, Sael; Ramos-Tovar, Erika; Flores-Beltrán, Rosa E; Arauz, Jonathan; Shibayama, Mineko; Favari, Liliana; Tsutsumi, Víctor; Segovia, José; Muriel, Pablo

    2017-06-28

    To study the molecular mechanisms involved in the hepatoprotective effects of naringenin (NAR) on carbon tetrachloride (CCl4)-induced liver fibrosis. Thirty-two male Wistar rats (120-150 g) were randomly divided into four groups: (1) a control group (n = 8) that received 0.7% carboxy methyl-cellulose (NAR vehicle) 1 mL/daily p.o.; (2) a CCl4 group (n = 8) that received 400 mg of CCl4/kg body weight i.p. 3 times a week for 8 wk; (3) a CCl4 + NAR (n = 8) group that received 400 mg of CCl4/kg body weight i.p. 3 times a week for 8 wk and 100 mg of NAR/kg body weight daily for 8 wk p.o.; and (4) an NAR group (n = 8) that received 100 mg of NAR/kg body weight daily for 8 wk p.o. After the experimental period, animals were sacrificed under ketamine and xylazine anesthesia. Liver damage markers such as alanine aminotransferase (ALT), alkaline phosphatase (AP), γ-glutamyl transpeptidase (γ-GTP), reduced glutathione (GSH), glycogen content, lipid peroxidation (LPO) and collagen content were measured. The enzymatic activity of glutathione peroxidase (GPx) was assessed. Liver histopathology was performed utilizing Masson's trichrome and hematoxylin-eosin stains. Zymography assays for MMP-9 and MMP-2 were carried out. Hepatic TGF-β, α-SMA, CTGF, Col-I, MMP-13, NF-κB, IL-1, IL-10, Smad7, Smad3, pSmad3 and pJNK proteins were detected via western blot. NAR administration prevented increases in ALT, AP, γ-GTP, and GPx enzymatic activity; depletion of GSH and glycogen; and increases in LPO and collagen produced by chronic CCl4 intoxication (P < 0.05). Liver histopathology showed a decrease in collagen deposition when rats received NAR in addition to CCl4. Although zymography assays showed that CCl4 produced an increase in MMP-9 and MMP-2 gelatinase activity; interestingly, NAR administration was associated with normal MMP-9 and MMP-2 activity (P < 0.05). The anti-inflammatory, antinecrotic and antifibrotic effects of NAR may be attributed to its ability to prevent NF

  8. [The effect of lumbar peridural anesthesia with catheter on the maternal and fetal acid-base status and the 1 minute apgar score (author's transl)].

    Science.gov (United States)

    Strasser, K; Harnacke, P; Albrecht, H; Morgenstern, J; Schmidt, H

    1975-06-01

    Comparison of 650 deliveries with P.A. and of 928 deliveries without P.A. during the same period. PH from the umbilical artery and 1 minute Apgar score were studied in three groups of patients: 1.) All deliveries, 2.) Spontaneous vaginal deliveries without maternal or fetal risk, 3.) Operative vaginal deliveries. The only significant differences were found among the operative vaginal deliveries: The infants of the peridural group showed a higher incidence of pH-values above 7,2 than those of the non peridural group. Analysis of the maternal acid-base status showed less respiratory alcalosis and less metabolic acidosis in the peridural group. The neonates of this group showed a lower post partum metabolic acidosis than those in the non peridural group.

  9. miR-200b-containing microvesicles attenuate experimental colitis associated intestinal fibrosis by inhibiting epithelial-mesenchymal transition.

    Science.gov (United States)

    Yang, Jia; Zhou, Cheng-Zhi; Zhu, Rui; Fan, Heng; Liu, Xing-Xing; Duan, Xue-Yun; Tang, Qing; Shou, Zhe-Xing; Zuo, Dong-Mei

    2017-12-01

    Epithelial-mesenchymal transition (EMT), characterized by the decrease of E-cadherin (E-Cad) and increase in vimentin and alpha-smooth muscle actin (α-SMA), was demonstrated to participate in inflammatory bowel disease-related fibrosis. miR-200b plays an anti-fibrosis role in inhibiting EMT by targeting ZEB1 and ZEB2. But the stability of exogenous miR-200b in blood limits its application. Microvesicles (MVs), which can transfer miRNAs among cells and prevent them from degradation, may provide an excellent transport system for the delivery of miR-200b in the treatment of fibrosis. Bone marrow mesenchymal stem cells (BMSCs) were transfected with lentivirus to overexpress miR-200b. The MVs packaged with miRNA-200b were harvested for the anti-fibrotic treatment using in vitro (transforming growth factor beta 1-mediated EMT in intestinal epithelial cells: IEC-6) and in vivo (TNBS-induced intestinal fibrosis in rats) models. The pathological morphology was observed, and the fibrosis related proteins, such as E-Cad, vimentin, α-SMA, ZEB1, and ZEB2, were detected. MiR-200b-MVs would significantly reverse the morphology in TGF-β1-treated IEC-6 cells and improve the TNBS-induced colon fibrosis histologically. The treatment of miR-200b-MVs increased miR-200b levels both in the IEC-6 cells and colon, resulting in a significant prevention EMT and alleviation of fibrosis. The expression of E-Cad was increased, and the expressions of vimentin and α-SMA were decreased. ZBE1 and ZEB2, the targets of miR-200b, were also decreased. miR-200b could be transferred from genetically modified BMSCs to the target cells or tissue by MVs. The mechanisms of miR-200b-MVs in inhibiting colonic fibrosis were related to suppressing the development of EMT by targeting ZEB1and ZEB2. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  10. Symbiotic formulation in experimentally induced liver fibrosis in rats: intestinal microbiota as a key point to treat liver damage?

    Science.gov (United States)

    D'Argenio, Giuseppe; Cariello, Rita; Tuccillo, Concetta; Mazzone, Giovanna; Federico, Alessandro; Funaro, Annalisa; De Magistris, Laura; Grossi, Enzo; Callegari, Maria L; Chirico, Marilena; Caporaso, Nicola; Romano, Marco; Morelli, Lorenzo; Loguercio, Carmela

    2013-05-01

    Evidence indicates that intestinal microbiota may participate in both the induction and the progression of liver damage. The aim of our research was the detection and evaluation of the effects of chronic treatment with a symbiotic formulation on CCl4 -induced rat liver fibrosis. CCl4 significantly increased gastric permeability in respect to basal values, and the treatment with symbiotic significantly decreased it. CCl4 per se induced a decrease in intestinal permeability. This effect was also seen in fibrotic rats treated with symbiotic and was still evident when normal rats were treated with symbiotic alone (P symbiotic treatment normalized the plasma levels of TNF-α and significantly enhanced anti-inflammatory cytokine IL 10. TNF-α, TGF-β, TLR4, TLR2, iNOS and α-SMA mRNA expression in the liver were up-regulated in rats with CCl4 -induced liver fibrosis and down-regulated by symbiotic treatment. Moreover, IL-10 and eNOS mRNA levels were increased in the CCL4 (+) symbiotic group. Symbiotic treatment of fibrotic rats normalized serum ALT, AST and improved histology and liver collagen deposition. DGGE analysis of faecal samples revealed that CCl4 administration and symbiotic treatment either alone or in combination produced modifications in faecal profiles vs controls. Our results provide evidence that in CCl4 -induced liver fibrosis, significant changes in gastro-intestinal permeability and in faecal flora occur. Treatment with a specific symbiotic formulation significantly affects these changes, leading to improvement in both liver inflammation and fibrosis. © 2013 John Wiley & Sons A/S.

  11. Experimental mild renal insufficiency mediates early cardiac apoptosis, fibrosis, and diastolic dysfunction: a kidney-heart connection.

    Science.gov (United States)

    Martin, Fernando L; McKie, Paul M; Cataliotti, Alessandro; Sangaralingham, S Jeson; Korinek, Josef; Huntley, Brenda K; Oehler, Elise A; Harders, Gerald E; Ichiki, Tomoko; Mangiafico, Sarah; Nath, Karl A; Redfield, Margaret M; Chen, Horng H; Burnett, John C

    2012-01-15

    Impaired renal function with loss of nephron number in chronic renal disease (CKD) is associated with increased cardiovascular morbidity and mortality. However, the structural and functional cardiac response to early and mild reduction in renal mass is poorly defined. We hypothesized that mild renal impairment produced by unilateral nephrectomy (UNX) would result in early cardiac fibrosis and impaired diastolic function, which would progress to a more global left ventricular (LV) dysfunction. Cardiorenal function and structure were assessed in rats at 4 and 16 wk following UNX or sham operation (Sham); (n = 10 per group). At 4 wk, blood pressure (BP), aldosterone, glomerular filtration rate (GFR), proteinuria, and plasma B-type natriuretic peptide (BNP) were not altered by UNX, representing a model of mild early CKD. However, UNX was associated with significantly greater LV myocardial fibrosis compared with Sham. Importantly, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining revealed increased apoptosis in the LV myocardium. Further, diastolic dysfunction, assessed by strain echocardiography, but with preserved LVEF, was observed. Changes in genes related to the TGF-β and apoptosis pathways in the LV myocardium were also observed. At 16 wk post-UNX, we observed persistent LV fibrosis and impairment in LV diastolic function. In addition, LV mass significantly increased, as did LVEDd, while there was a reduction in LVEF. Aldosterone, BNP, and proteinuria were increased, while GFR was decreased. The myocardial, structural, and functional alterations were associated with persistent changes in the TGF-β pathway and even more widespread changes in the LV apoptotic pathway. These studies demonstrate that mild renal insufficiency in the rat results in early cardiac fibrosis and impaired diastolic function, which progresses to more global LV remodeling and dysfunction. Thus, these studies importantly advance the concept of a kidney

  12. Retroperitoneal fibrosis

    Science.gov (United States)

    ... Names Idiopathic retroperitoneal fibrosis; Ormond's disease Images Male urinary system References Nakada SY, Best SL. Management of upper urinary tract obstruction. In: Wein AJ, Kavoussi LR, Partin ...

  13. Peridural injection of Mailuoning compound liquor for treatment of prolapse of lumbar intervertebral disc in 100 cases.

    Science.gov (United States)

    Zhi, Man-xia; Zhang, Guo-bin; Hou, Jin-cai; Yang, Yu-hong; Wan, Zheng-zuo

    2009-03-01

    To observe the therapeutic effects of peridural injection of Mailuoning Compound Liquor for prolapse of lumbar intervertebral disc (PLID). Peridural injection of Mailuoning Compound Liquor (MCL) was given to 100 cases of PLID, once a week, 4 sessions constituting a therapeutic course. By adopting the scoring method, observations were carried out on the total therapeutic effect and changes in the 13 items of the symptoms and signs. After treatment, the JOA scores in this series of patients were markedly enhanced as compared with the scores before treatment, showing significant differences in the paired t test (P<0.05). The sum of the excellent and good rates was 64%, and the total effective rate was 97%. All the scores in the 13 items under observation were significantly raised as compared with the scores before treatment (P<0.05). Peridural injection of MCL is an effective and safe therapy for PLID, and with shorter treating course, quicker therapeutic effects, and less suffering for the patients.

  14. Learn About Pulmonary Fibrosis

    Science.gov (United States)

    ... Events Become An Advocate Volunteer Ways To Give Pulmonary Fibrosis www.lung.org > Lung Health and Diseases > Lung ... Pulmonary Fibrosis > Introduction Share this page: Introduction to Pulmonary Fibrosis What Is Pulmonary Fibrosis? Pulmonary fibrosis is a ...

  15. Tight blood glycaemic and blood pressure control in experimental diabetic nephropathy reduces extracellular matrix production without regression of fibrosis.

    Science.gov (United States)

    Conway, Bryan R; Betz, Boris; Sheldrake, Tara A; Manning, Jonathan R; Dunbar, Donald R; Dobyns, Abigail; Hughes, Jeremy; Mullins, John J

    2014-12-01

    Regression of albuminuria and renal fibrosis occurs in patients with diabetic nephropathy (DN) following tight control of blood glucose and blood pressure, however the pathways that promote regression remain poorly understood and we wished to characterize these using a rodent model. Diabetes was induced with streptozotocin in Cyp1a1mRen2 rats and hypertension was generated by inducing renin transgene expression with dietary indole-3-carbinol (I-3-C) for 28 weeks. At this point an 'injury cohort' was culled, while in a 'reversal cohort' glycaemia was tightly controlled using insulin implants and blood pressure normalized by withdrawing dietary I-3-C for a further 8 weeks. Pathways activated during and following reversal of diabetes and hypertension were assessed by microarray profiling. Tight control of blood glucose and blood pressure reduced albuminuria and renal hypertrophy, but had no impact on renal fibrosis. 85 genes were up-regulated specifically during the injury phase, including genes encoding multiple myofibroblast and extracellular matrix (ECM) proteins. Conversely, 314 genes remained persistently elevated during reversal including genes linked to innate/adaptive immunity, phagocytosis, lysosomal processing and degradative metalloproteinases (MMPs). Despite increased MMP gene expression, MMP activity was suppressed during both injury and reversal, in association with up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) protein. Physical separation of the TIMP-1/MMP complexes during zymography of tissue homogenate restored MMP activity. Normalization of blood glucose and pressure ameliorates albuminuria and inhibits excess ECM production, however persistent TIMP-1 expression hinders attempts at ECM remodelling. Therapies which counteract the action of TIMPs may accelerate scar resolution. © 2014 Asian Pacific Society of Nephrology.

  16. Effect of Cardiac Resynchronization Therapy on Myocardial Fibrosis and Relevant Cytokines in a Canine Model With Experimental Heart Failure.

    Science.gov (United States)

    Wang, Jingfeng; Gong, Xue; Chen, Haiyan; Qin, Shengmei; Zhou, Nianwei; Su, Yangang; Ge, Junbo

    2017-04-01

    Though cardiac resynchronization therapy (CRT) has now proved to be effective on cardiac reverse remodeling, data on the underlying molecular changes are limited. The present study aims to investigate the expression of cytokines concerning myocardial fibrosis in dyssynchronous heart failure (HF) and the potential benefits of CRT. Left bundle branch ablation and rapid pacing was performed to induce a canine model of asynchronous HF. Animals were randomly divided into sham group, HF control group, and CRT group. Echocardiographic data including septum-to-posterior wall motion delay (SPWMD) and standard deviation of the time to peak systolic velocity (Ts-SD) were collected. Histologic samples from lateral left ventricular (LV) and right ventricular (RV) free wall were analyzed and compared among different groups. Serum concentrations of NT-proBNP, TGF-β1 , and osteopontin (OPN) were measured using enzyme-linked immunosorbent assay (ELISA). Protein and mRNA expressions of TGF-β1 /Smad and OPN from myocardial tissues were also detected and compared. CRT improved cardiac function and corrected intraventricular dyssynchrony with increased LV ejection fraction (LVEF) and decreased SPWMD and Ts-SD (P < 0.05). Histological analysis showed that CRT restored cardiomyocyte diameter (from 4.50 to 6.08 μm) and collagen volume fraction (from 19.33% to 11.21%) of LV (P < 0.01), but had little effect on RV. Serum TGF-β1 and OPN level were also reversed toward normal level after CRT (P < 0.05). Compared with sham group, a significantly higher protein and mRNA expressions of TGF-β1 /Smad and OPN were observed in HF control group, which were significantly downregulated in CRT group (P < 0.01). By means of coordinating LV dyssynchrony, cellular and molecular reverse remodeling relevant to fibrosis inhibition could also be invoked by CRT. © 2017 Wiley Periodicals, Inc.

  17. Uso do bloqueio combinado raqui-peridural durante cirurgia de cólon em paciente de alto risco: relato de caso

    OpenAIRE

    Imbelloni, Luiz Eduardo; Fornasari, Marcos; Fialho, José Carlos

    2009-01-01

    JUSTIFICATIVA E OBJETIVOS: O bloqueio combinado raqui-peridural (BCRP) oferece vantagens sobre a anestesia peridural ou subaracnóidea com injeção única. O objetivo deste relato foi apresentar um caso onde a anestesia subaracnóidea segmentar pode ser técnica efetiva para intervenção cirúrgica gastrintestinal com respiração espontânea. RELATO DO CASO: Paciente estado físico ASA III, diabetes mellitus tipo II, com hipertensão arterial sistêmica e doença pulmonar obstrutiva crônica, foi escalada ...

  18. The anti-fibrotic effect of inhibition of TGFβ-ALK5 signalling in experimental pulmonary fibrosis in mice is attenuated in the presence of concurrent γ-herpesvirus infection

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    Natalia Smoktunowicz

    2015-09-01

    Full Text Available TGFβ-ALK5 pro-fibrotic signalling and herpesvirus infections have been implicated in the pathogenesis and exacerbation of pulmonary fibrosis. In this study we addressed the role of TGFβ-ALK5 signalling during the progression of fibrosis in a two-hit mouse model of murine γ-herpesvirus 68 (MHV-68 infection on the background of pre-existing bleomycin-induced pulmonary fibrosis. Assessment of total lung collagen levels in combination with ex vivo micro-computed tomography (µCT analysis of whole lungs demonstrated that MHV-68 infection did not enhance lung collagen deposition in this two-hit model but led to a persistent and exacerbated inflammatory response. Moreover, µCT reconstruction and analysis of the two-hit model revealed distinguishing features of diffuse ground-glass opacities and consolidation superimposed on pre-existing fibrosis that were reminiscent of those observed in acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF. Virally-infected murine fibrotic lungs further displayed evidence of extensive inflammatory cell infiltration and increased levels of CCL2, TNFα, IL-1β and IL-10. Blockade of TGFβ-ALK5 signalling attenuated lung collagen accumulation in bleomycin-alone injured mice, but this anti-fibrotic effect was reduced in the presence of concomitant viral infection. In contrast, inhibition of TGFβ-ALK5 signalling in virally-infected fibrotic lungs was associated with reduced inflammatory cell aggregates and increased levels of the antiviral cytokine IFNγ. These data reveal newly identified intricacies for the TGFβ-ALK5 signalling axis in experimental lung fibrosis, with different outcomes in response to ALK5 inhibition depending on the presence of viral infection. These findings raise important considerations for the targeting of TGFβ signalling responses in the context of pulmonary fibrosis.

  19. Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis

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    Cheri L. Lamb

    2016-01-01

    Full Text Available The aryl hydrocarbon receptor (AhR is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD. Increasing evidence implicates the AhR in regulating extracellular matrix (ECM homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl4. However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl4-treated mice, which raises the possibility that TCDD may enhance ECM turnover. The goal of this study was to determine how TCDD impacts ECM remodeling gene expression in the liver. Male C57BL/6 mice were treated for 8 weeks with 0.5 mL/kg CCl4, and TCDD (20 μg/kg was administered during the last two weeks. Results indicate that TCDD increased mRNA levels of procollagen types I, III, IV, and VI and the collagen processing molecules HSP47 and lysyl oxidase. TCDD also increased gelatinase activity and mRNA levels of matrix metalloproteinase- (MMP- 3, MMP-8, MMP-9, and MMP-13. Furthermore, TCDD modulated expression of genes in the plasminogen activator/plasmin system, which regulates MMP activation, and it also increased TIMP1 gene expression. These findings support the notion that AhR activation by TCDD dysregulates ECM remodeling gene expression and may facilitate ECM metabolism despite increased liver injury.

  20. Living with Cystic Fibrosis

    Science.gov (United States)

    ... Research Home / Cystic Fibrosis Cystic Fibrosis What Is Cystic fibrosis (SIS-tik fi-BRO- ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  1. What is Cystic Fibrosis?

    Science.gov (United States)

    ... Research Home / Cystic Fibrosis Cystic Fibrosis What Is Cystic fibrosis (SIS-tik fi-BRO- ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  2. What Causes Cystic Fibrosis?

    Science.gov (United States)

    ... Research Home / Cystic Fibrosis Cystic Fibrosis What Is Cystic fibrosis (SIS-tik fi-BRO- ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  3. Hematoma após anestesia peridural: tratamento conservador. Relato de caso Hematoma posterior a la anestesia peridural: tratamiento conservador. Relato de caso Hematoma after epidural anesthesia: conservative treatment. Case report

    Directory of Open Access Journals (Sweden)

    Edno Magalhães

    2007-04-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O hematoma associado à compressão espinhal após anestesia peridural é uma complicação neurológica grave, apesar da pequena incidência relatada (1:150.000. É um episódio agudo, e o tratamento tradicionalmente aplicado é a descompressão cirúrgica de urgência. Mais recentemente, em casos específicos, o tratamento com corticosteróide tem sido aplicado como alternativa, com boa recuperação neurológica. O objetivo deste relato foi expor um caso de hematoma peridural com tratamento conservador e recuperação neurológica completa. RELATO DO CASO: Paciente do sexo feminino, 34 anos, estado físico ASA I, sem qualquer histórico de coagulopatia ou terapia anticoagulante, submetida à anestesia peridural com punção única, em L2-L3, para tratamento cirúrgico de varizes nos membros inferiores. Oito horas após a anestesia regional, ela ainda apresentava bloqueio motor completo (escala de Bromage, redução das sensibilidades térmica e dolorosa abaixo do nível L3, hiperalgesia na região plantar esquerda, preservação dos reflexos tendinosos e ausência de dor lombar. A tomografia computadorizada revelou hematoma peridural em L2 com compressão do saco dural. Dez horas após a punção peridural não havia progressão dos sinais e sintomas neurológicos. Optou-se, então, pelo tratamento com metilprednisolona em infusão venosa contínua (5,3 mg.kg-1 na primeira hora e 1,4 mg.kg-1.h-1 nas 23 horas subseqüentes. Oito horas após o início do tratamento, a paciente recuperou as sensibilidades térmica e dolorosa, e houve regressão total do bloqueio motor. Na 12ª hora, deambulava e referia dor na ferida operatória. O hematoma peridural não foi visualizado em nova tomografia computadorizada na 14ª hora após o início do tratamento. A paciente recebeu alta hospitalar 86 horas depois do início do tratamento conservador, sem comprometimento neurológico. Uma tomografia computadorizada de controle, ap

  4. Analgesia pós-toracotomia com associação de morfina por via peridural e venosa

    Directory of Open Access Journals (Sweden)

    Fonseca Neuber Martins

    2002-01-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Analgesia após cirurgia de tórax é feita por diferentes métodos. O objetivo do estudo foi avaliar a analgesia pós-operatória com associação de morfina por via venosa e peridural, comparada ao uso por via isolada. MÉTODO: Foram estudados 20 pacientes submetidos à cirurgia de tórax, ambos os sexos, estado físico ASA I a III. Foi feita medicação pré-anestésica com midazolam por via venosa (3 a 3,5 mg na SO. A monitorização constou de ECG contínuo, pressão arterial invasiva, oximetria de pulso, capnografia, PVC, diurese e temperatura. Primeiramente foi realizada anestesia peridural contínua, T7-T8 com 10 ml de bupivacaína a 0,25% e, em seguida, indução com fentanil (5 µg.kg-1, etomidato (0,2 a 0,3 mg.kg-1 e succinilcolina (1 mg.kg-1. Foi feita IOT com tubo de duplo lume, complementação com pancurônio (0,08 a 0,1 mg.kg-1 e ventilação controlada mecânica. Os pacientes foram então distribuídos aleatoriamente em três grupos. Ao Grupo I, administrou-se pelo cateter peridural, 2 mg de morfina 0,1% na indução da anestesia (M1, após 12 horas (M2 e 24 horas (M3 do final da cirurgia, ao Grupo II, morfina por via venosa em bomba de infusão (15 µg.kg.h-1 precedida de bolus de 50 µg.kg-1, durante 30 horas e ao Grupo III, morfina por via peridural na dose de 0,5 mg em M1, M2 e M3, associada com morfina venosa em bomba de infusão (8 µg.kg.h-1 precedida de bolus de 25 µg.kg-1, por 30 horas. Análise de gases arteriais, freqüências cardíaca e respiratória, presença de prurido, náuseas, vômitos e analgesia pós-operatória foram avaliados a cada 6 horas, até um total de 30 horas do pós-operatório. A analgesia foi avaliada por escala de graduação numérica (EGN de 0 a 10. RESULTADOS: A EGN apresentou redução no grupo I apenas no momento M2 não ocorrendo nos demais intervalos. Nos grupos II e III ocorreu redução da dor a partir de 18 horas em relação aos valores iniciais e em rela

  5. Peritoneal fibrosis

    Directory of Open Access Journals (Sweden)

    Horacio Alfredo Trevisani

    2017-04-01

    Full Text Available The peritoneal dialysis (PD is one way of renal function's substitution and as a treatment, it covers more than 100,000 patients with stage V chronic kidney disease worldwide, so the prevalence rate ranges from 10 to 15% of the dialysis population. The biggest obstacles to the long-term therapy are infections and disorders suffered by the peritoneal membrane when exposed to dialytic solutions that generate loss of dialysis capacity in both diffusion and ultrafiltration. These changes can affect almost 50% of patients on dialysis. They include progressive fibrosis, angiogenesis and vascular degeneration. In a small percentage fibrosis occurs in the visceral peritoneum leading to their worst performance: encapsulating peritoneal sclerosis, with a high mortality rate. Being acquainted with the pathophysiology of these disorders, causes changes in the use of therapy to prevent the appearance, progression to fibrosis and thus reduce the drop-out of the technique due to peritoneal exhaustion. In this article some of the mechanisms of production and possible measures to reduce appearance of peritoneal fibrosis will be reviewed.

  6. Understanding Nephrogenic Systemic Fibrosis

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    Tushar Chopra

    2012-01-01

    Full Text Available Nephrogenic systemic fibrosis (NSF is a rare and a debilitating disease noted uncommonly in patients with impaired renal function when exposed to low-stability gadolinium-based contrast agents (Gd-CAs. According to experimental studies, cytokines released by the stimulation of effector cells such as skin macrophages and peripheral blood monocytes activate circulating fibroblasts which play a major role in the development of NSF lesions. The presence of permissive factors, presumably, provides an environment conducive to facilitate the process of fibrosis. Multiple treatment modalities have been tried with variable success rates. More research is necessary to elucidate the underlying pathophysiological mechanisms which could potentially target the initial steps of fibrosis in these patients. This paper attempts to collate the inferences from the in vivo and in vitro experiments to the clinical observations to understand the pathogenesis of NSF. Schematic representations of receptor-mediated molecular pathways of activation of macrophages and fibroblasts by gadolinium and the final pathway to fibrosis are incorporated in the discussion.

  7. Facet blockade, peridural and periradicular pain therapy; Facettenblockade, peridurale und periradikulaere Schmerztherapie

    Energy Technology Data Exchange (ETDEWEB)

    Waggershauser, T.; Reiser, M. [Klinikum Grosshadern der Ludwig-Maximilians-Universitaet, Institut fuer klinische Radiologie, Muenchen (Germany); Schwarzkopf, S. [Klinikum der Ludwig-Maximilians-Universitaet, Institut fuer Gesundheits- und Rehabilitationswissenschaften, Muenchen (Germany)

    2006-06-15

    More than 80% of vertebrogenic lumbar pain is unspecific and can only be attributed to a specific anatomic structure with difficulty. The pain can emanate from the intervertebral discs, intervertebral and sacroiliac (SI) joints, musculature, and ligaments. In a maximum of 7% of cases, the pain is radicular (4% due to intervertebral discs and 3% caused by stenoses). In 7-15% of cases, the pain's origin is located in the region of the vertebral joints and in up to 15% in the region of the SI joint. Although the overwhelming majority of pain has no clear structural cause, infiltrations of medications and nerve blockades are frequently employed. The efficacy of these procedures has however not been verified in controlled studies with the exception of epidural injection of corticosteroids for radicular pain. Epidural and epiradicular application of corticosteroids appear to be effective for radicular pain, at least on a short-term basis, although controlled studies have yielded controversial results. The difficulty lies partly in the exact placement at the affected root for applying the medication. This is hardly possible with a caudal injection, while with a lumbar peridural injection and periradicular injections it is only possible under X-ray control or even better CT guidance. (orig.) [German] Mehr als 80% der vertebragenen lumbalen Schmerzen sind unspezifisch und koennen nur schwer einer bestimmten anatomischen Struktur zugeordnet werden. Die Schmerzen koennen von den Bandscheiben, den Zwischenwirbel- und Iliosakralgelenken, der Muskulatur und den Baendern ausgehen. In hoechstens 7% der Faelle sind die Schmerzen radikulaer (4% durch Bandscheiben, 3% durch Stenosen). In 7-15% der Faelle liegt die Schmerzursache im Bereich der Wirbelgelenke, in bis zu 15% im Bereich der Iliosakralgelenke (ISG). Obschon die ueberwaeltigende Mehrheit der Schmerzen keine eindeutige strukturelle Ursache hat, werden Infiltrationen von Medikamenten und Nervenblockaden haeufig

  8. [Retroperitoneal fibrosis].

    Science.gov (United States)

    Babski, Paweł; Wojtuń, Stanisław; Gil, Jerzy

    2007-05-01

    Retroperitoneal fibrosis is a rare clinical entity characterised by the presence of patologic collagen tissue in a retroperitoneal space. The fibrous mass covers abdominal organs causing their disfunctions. RPF was described at the begining of XX century but its etiology is not clear yet. Usually it causes an ureter obstuction and hydronephrosis, that is why most commonly is diagnosed by urologists and nephrologists. However, retroperitoneal fibrosis can be multifacial disease. In some patients localisation of fibrosis is atypical and manifestationns can be varied. Gastrological symptoms like jaundice, bowel obstuction, ascites can occure. Besides, some early signs of RPF are nonspecific and can imitate alarming symptoms of neoplasma, e.g.: weight loss, anemia, malaise, anorexia, fever. This force us to initiate gastrological investigation. The awareness of this disease is important. The early diagnosis and treatment improves prognosis and alows to avoid heavy complications. In typical cases radiology is often enough for diagnosis. However, histological examination is needed in many cases, especialy when patological mass is located atypical. A treatment is made up of farmacology and surgery. The first one is based on steroids, immunossuppressant and tamoxifen. Surgery is needed to eliminate organs obstruction.

  9. Pulmonary Fibrosis Foundation

    Science.gov (United States)

    ... the most current news and updates from the Pulmonary Fibrosis Foundation. Life with PF Education & Support About PF ... abstract submissions. MORE We Imagine a World Without Pulmonary Fibrosis The Pulmonary Fibrosis Foundation mobilizes people and resources ...

  10. Familial Pulmonary Fibrosis

    Science.gov (United States)

    ... Education & Training Home Conditions Familial Pulmonary Fibrosis Familial Pulmonary Fibrosis Make an Appointment Find a Doctor Ask a ... more members within the same family have Idiopathic Pulmonary Fibrosis (IPF) or any other form of Idiopathic Interstitial ...

  11. Transplacental Distribution of Lidocaine and Its Metabolite in Peridural Anesthesia Administered to Patients With Gestational Diabetes Mellitus

    Science.gov (United States)

    Duarte, Luciana de Barros; Cavalli, Ricardo de Carvalho; Carvalho, Daniela Miarelli; Filgueira, Gabriela Campos de Oliveira; Marques, Maria Paula; Lanchote, Vera Lucia; Duarte, Geraldo

    2015-01-01

    Background: Neonatal effects of drugs administered to mothers before delivery depend on the quantity that crosses the placental barrier, which is determined by the pharmacokinetics of the drug in the mother, fetus, and placenta. Diabetes mellitus can alter the kinetic disposition and the metabolism of drugs. This study investigated the placental transfer of lidocaine and its metabolite monoethylglycinexylidide (MEGX) in pregnant women with gestational diabetes mellitus (GDM) submitted to peridural anesthesia. Patients and Methods: A total of 10 normal pregnant women (group 1) and 6 pregnant women with GDM (group 2) were studied, all at term. The patients received 200 mg 2% lidocaine hydrochloride by the peridural locoregional route. Maternal blood samples were collected at the time of delivery and, after placental expulsion, blood samples were collected from the intervillous space, umbilical artery, and vein for determination of lidocaine and MEGX concentrations and analysis of the placental transfer of the drug. Results: The following respective lidocaine ratios between the maternal and the fetal compartments were obtained for groups 1 and 2: umbilical vein/maternal peripheral blood, 0.60 and 0.46; intervillous space/maternal blood, 1.01 and 0.88; umbilical artery/umbilical vein, 0.77 and 0.91; and umbilical vein/intervillous space, 0.53 and 0.51. The following MEGX ratios for groups 1 and 2 were, respectively, fetal/maternal, 0.43 and 0.97; intervillous space/maternal blood, 0.64 and 0.90; umbilical artery/umbilical vein, 1.09 and 0.99; and umbilical vein/intervillous space, 0.55 and 0.78. Conclusion: Gestational diabetes mellitus did not affect the transplacental transfer of lidocaine but interfered with the transfer of MEGX, acting as a mechanism facilitating the transport of the metabolite. PMID:25563756

  12. Peridural torácica alta associada ou não à peridural torácica baixa em pacientes ambulatoriais: implicações clínicas Peridural torácica alta asociada o no a la peridural torácica baja en pacientes ambulatoriales: implicaciones clínicas High thoracic epidural anesthesia associated or not to low thoracic epidural anesthesia in outpatient procedures: clinical implications

    Directory of Open Access Journals (Sweden)

    Djalma Sperhacke

    2004-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Sob bloqueio peridural torácico baixo ou médio, as alterações hemodinâmicas são facilmente controladas. Como o bloqueio peridural torácico alto (T2-T3 acomete, freqüentemente, as raízes do plexo braquial (C4C5-T1(T2, algumas destas responsáveis pela formação do nervo frênico (C3-C4-C5 é de se supor, possíveis repercussões motoras deste último. O presente estudo realizado em cirurgias estéticas, sob bloqueio peridural segmentar isolado em T2-T3 ou associado ao bloqueio peridural segmentar em T11-T12, avaliou as repercussões motoras na dinâmica respiratória assim como nos membros superiores e inferiores. MÉTODO: Trinta e duas pacientes, estado físico ASA I e II, sem doença pulmonar broncoespástica, em atividade e peso corporal igual ou superior a 50 kg, foram submetidas a 21 bloqueios peridurais torácicos isolados em T2-T3 e as 11 restantes, a bloqueios combinados em T11-T12, com ropivacaína a 7,5% (45 a 90 mg associada ao sufentanil (10 a 20 µg. Repercussões hemodinâmicas, respiratórias e motoras nos membros superiores e inferiores foram avaliadas respectivamente, sob monitorização não-invasiva, espirometria, força de preensão da mão e escala de Bromage. RESULTADOS: A média de duração das cirurgias mamárias foi de 105 minutos com depressão motora dos membros superiores (p JUSTIFICATIVA Y OBJETIVOS: Sobre bloqueo peridural torácico bajo o medio, las alteraciones hemodinâmicas son fácilmente controladas. Como el bloqueo peridural torácico alto (T2-T3 acomete, frecuentemente, las raíces del plexo braquial (C4C5-T1(T2, algunas de estas responsables por la formación del nervio frénico (C3-C4-C5 es de suponer, posibles repercusiones motoras de este último. El presente estudio realizado en cirugías estéticas, sobre bloqueo peridural segmentar aislado en T2-T3 o asociado al bloqueo peridural segmentar en T11-T12, evaluó las repercusiones motoras en la dinámica respiratoria

  13. Transplacental Distribution of Lidocaine and Its Metabolite in Peridural Anesthesia Administered to Patients With Gestational Diabetes Mellitus.

    Science.gov (United States)

    Moises, Elaine Christine Dantas; Duarte, Luciana de Barros; Cavalli, Ricardo de Carvalho; Carvalho, Daniela Miarelli; Filgueira, Gabriela Campos de Oliveira; Marques, Maria Paula; Lanchote, Vera Lucia; Duarte, Geraldo

    2015-07-01

    Neonatal effects of drugs administered to mothers before delivery depend on the quantity that crosses the placental barrier, which is determined by the pharmacokinetics of the drug in the mother, fetus, and placenta. Diabetes mellitus can alter the kinetic disposition and the metabolism of drugs. This study investigated the placental transfer of lidocaine and its metabolite monoethylglycinexylidide (MEGX) in pregnant women with gestational diabetes mellitus (GDM) submitted to peridural anesthesia. A total of 10 normal pregnant women (group 1) and 6 pregnant women with GDM (group 2) were studied, all at term. The patients received 200 mg 2% lidocaine hydrochloride by the peridural locoregional route. Maternal blood samples were collected at the time of delivery and, after placental expulsion, blood samples were collected from the intervillous space, umbilical artery, and vein for determination of lidocaine and MEGX concentrations and analysis of the placental transfer of the drug. The following respective lidocaine ratios between the maternal and the fetal compartments were obtained for groups 1 and 2: umbilical vein/maternal peripheral blood, 0.60 and 0.46; intervillous space/maternal blood, 1.01 and 0.88; umbilical artery/umbilical vein, 0.77 and 0.91; and umbilical vein/intervillous space, 0.53 and 0.51. The following MEGX ratios for groups 1 and 2 were, respectively, fetal/maternal, 0.43 and 0.97; intervillous space/maternal blood, 0.64 and 0.90; umbilical artery/umbilical vein, 1.09 and 0.99; and umbilical vein/intervillous space, 0.55 and 0.78. Gestational diabetes mellitus did not affect the transplacental transfer of lidocaine but interfered with the transfer of MEGX, acting as a mechanism facilitating the transport of the metabolite. © The Author(s) 2015.

  14. Ocorrência de hematoma peridural após anestesia geral associada à analgesia pós-operatória com cateter peridural em paciente em uso de heparina de baixo peso molecular: relato de caso Ocurrencia de hematoma postanestesia general asociada a analgesia postoperatoria con cateter peridural en paciente que usa heparina de bajo peso molecular: relato de caso Epidural hematoma after general anesthesia associated with postoperative analgesia with epidural catheter in patient using low molecular weight heparin: case report

    Directory of Open Access Journals (Sweden)

    Ranger Cavalcante da Silva

    2006-04-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Apresentar um caso de paciente com hematoma peridural, na vigência do uso de cateter peridural e heparina de baixo peso molecular, seu quadro clínico e tratamento. RELATO DO CASO: Paciente do sexo feminino, 75 anos, submetida à fixação de coluna lombar por via anterior, que desenvolveu no pós-operatório quadro clínico de paralisia progressiva nos membros inferiores, com perda de sensibilidade, sem apresentar dor radicular intensa. O tratamento foi descompressão medular imediata, com drenagem e limpeza cirúrgica de hematoma peridural, que se estendia da quinta até a décima vértebra torácica. Após a drenagem do hematoma a paciente recuperou gradualmente a força nos membros inferiores, recebeu alta em 10 dias com quadro de disfunção esfincteriana. Após três meses o quadro regrediu e não houve seqüela neurológica definitiva. CONCLUSÕES: O rápido diagnóstico com intervenção cirúrgica precoce é o tratamento mais eficaz para redução de lesão neurológica, em pacientes que desenvolvem hematoma peridural no pós-operatório. A utilização de heparina de baixo peso molecular, na vigência do uso de cateter peridural, exige a adesão estrita a protocolos estabelecidos, para que se reduzam os riscos do desenvolvimento de hematoma peridural.JUSTIFICATIVA Y OBJETIVOS: presentar el caso de una paciente con hematoma peridural, con uso actual de catéter peridural y heparina de bajo peso molecular, su cuadro clínico y tratamiento. RELATO DEL CASO: Paciente de 75 años, sometida a la fijación de columna lumbar por vía anterior, que desarrolló en el postoperatorio un cuadro clínico de parálisis progresiva en los miembros inferiores, con pérdida de la sensibilidad, sin presentar dolor radicular intenso. El tratamiento fue descompresión medular inmediata, con drenaje y limpieza quirúrgica de un hematoma peridural, que se extendía desde la quinta hasta la décima vértebra toráxica. Después del

  15. Kinin B1 receptor antagonism is equally efficient as angiotensin receptor 1 antagonism in reducing renal fibrosis in experimental obstructive nephropathy, but is not additive.

    Directory of Open Access Journals (Sweden)

    Antoine eHuart

    2015-02-01

    Full Text Available Background: Renal tubulointerstitial fibrosis is the pathological hallmark of chronic kidney disease. Currently, inhibitors of the renin angiotensin system (RAS remain the sole therapy in human displaying antifibrotic properties. Further antifibrotic molecules are needed. We have recently reported that the delayed blockade of the bradykinin B1 receptor (B1R reduced the development of fibrosis in two animal models of renal fibrosis. The usefulness of new drugs also resides in outperforming the gold standards and eventually being additive or complementary to existing therapies. Methods: In this study we compared the efficacy of a B1R antagonist (B1Ra with that of an angiotensin type 1 receptor antagonist (AT1a in the unilateral ureteral obstruction (UUO model of renal fibrosis and determined whether bi-therapy presented higher efficacy than any of the drugs alone. Results: B1R antagonism was as efficient as the gold-standard AT1a treatment. However bitherapy did not improve the antifibrotic effects at the protein level. We sought for the reason of the absence of this additive effect by studying the expression of a panel of genes involved in the fibrotic process. Interestingly, at the molecular level the different drugs targeted different players of fibrosis that, however, in this severe model did not result in improved reduction of fibrosis at the protein level. Conclusions: As the B1R is induced specifically in the diseased organ and thus potentially displays low side effects it might be an interesting alternative in cases of poor tolerability to RAS inhibitors.

  16. Kinin B1 receptor antagonism is equally efficient as angiotensin receptor 1 antagonism in reducing renal fibrosis in experimental obstructive nephropathy, but is not additive

    Science.gov (United States)

    Huart, Antoine; Klein, Julie; Gonzalez, Julien; Buffin-Meyer, Bénédicte; Neau, Eric; Delage, Christine; Calise, Denis; Ribes, David; Schanstra, Joost P.; Bascands, Jean-Loup

    2015-01-01

    Background: Renal tubulointerstitial fibrosis is the pathological hallmark of chronic kidney disease (CKD). Currently, inhibitors of the renin–angiotensin system (RAS) remain the sole therapy in human displaying antifibrotic properties. Further antifibrotic molecules are needed. We have recently reported that the delayed blockade of the bradykinin B1 receptor (B1R) reduced the development of fibrosis in two animal models of renal fibrosis. The usefulness of new drugs also resides in outperforming the gold standards and eventually being additive or complementary to existing therapies. Methods: In this study we compared the efficacy of a B1R antagonist (B1Ra) with that of an angiotensin type 1 receptor antagonist (AT1a) in the unilateral ureteral obstruction (UUO) model of renal fibrosis and determined whether bi-therapy presented higher efficacy than any of the drugs alone. Results: B1R antagonism was as efficient as the gold-standard AT1a treatment. However, bitherapy did not improve the antifibrotic effects at the protein level. We sought for the reason of the absence of this additive effect by studying the expression of a panel of genes involved in the fibrotic process. Interestingly, at the molecular level the different drugs targeted different players of fibrosis that, however, in this severe model did not result in improved reduction of fibrosis at the protein level. Conclusions: As the B1R is induced specifically in the diseased organ and thus potentially displays low side effects it might be an interesting alternative in cases of poor tolerability to RAS inhibitors. PMID:25698969

  17. Ropivacaína isolada e associada ao fentanil ou ao tramadol administrados pela via peridural em cães Ropivacaine individually and in combination with fentanyl or tramadol, administered by peridural via in dogs

    Directory of Open Access Journals (Sweden)

    Bruno Monteiro da Silva

    2008-11-01

    Full Text Available A anestesia peridural é amplamente difundida no meio veterinário, utilizando-se o anestésico local isolado ou associado aos opióides, capazes de promover aumento do efeito analgésico. O objetivo deste estudo foi avaliar a função cardiorrespiratória e analgésica da ropivacaína isolada ou associada ao fentanil ou tramadol. Para tanto, oito cães foram tranqüilizados com acepromazina, submetidos à anestesia peridural com um dos seguintes protocolos: GR (ropivacaína, GRF (ropivacaína + fentanil, GRT (ropivacaína + tramadol, em volume total de 0,25ml kg-1, e foram avaliados os parâmetros: freqüência cardíaca e respiratória, temperatura retal, pressão arterial sistólica, e gasometria do sangue arterial, os bloqueios sensitivo e motor, o grau de sedação e a ocorrência de possíveis efeitos indesejáveis. A diminuição da freqüência cardíaca nos grupos GRF e GRT foi mais intensa e ocorreu hipotermia significativa no GRF. Foi evidenciada sedação severa em GRF e GRT. O período de recuperação foi mais curto nos animais de GRT. O GRT foi o grupo que apresentou bloqueio mais cranial. Foram observadas bradicardia, hipotermia e síndrome de Shiff-Sherrington no período trans-anestésico em animais de todos os grupos. Nas 24 horas de período pós-anestésico, não foram evidenciados efeitos indesejáveis nos grupos. O GRF apresentou maior duração de anestesia e analgesia, enquanto que o GRT apresentou a menor duração de anestesia com analgesia intermediária e o GR apresentou duração intermediária, com menor analgesia. Não foram encontradas alterações respiratórias e hemogasométricas, porém, bradicardia, hipotermia e síndrome de Schiff-Sherrington, alterações trans-anestésicas comuns na anestesia peridural foram encontradas.Peridural anesthesia is broadly applied in the Veterinary field, using the isolated local anesthetic or in combination with opiates capable to increase the analgesic effect. This research

  18. Biomarkers for liver fibrosis

    Science.gov (United States)

    Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

    2015-09-15

    Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

  19. Biomarkers for liver fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

    2017-05-16

    Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

  20. Loss of Twist1 in the Mesenchymal Compartment Promotes Increased Fibrosis in Experimental Lung Injury by Enhanced Expression of CXCL12

    Science.gov (United States)

    Tan, Jiangning; Tedrow, John R.; Nouraie, Mehdi; Dutta, Justin A.; Miller, David T.; Li, Xiaoyun; Yu, Shibing; Chu, Yanxia; Juan-Guardela, Brenda; Kaminski, Naftali; Ramani, Kritika; Biswas, Partha S.; Zhang, Yingze

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a disease characterized by the accumulation of apoptosis-resistant fibroblasts in the lung. We have previously shown that high expression of the transcription factor Twist1 may explain this prosurvival phenotype in vitro. However, this observation has never been tested in vivo. We found that loss of Twist1 in COL1A2+ cells led to increased fibrosis characterized by very significant accumulation of T cells and bone marrow–derived matrix-producing cells. We found that Twist1-null cells expressed high levels of the T cell chemoattractant CXCL12. In vitro, we found that the loss of Twist1 in IPF lung fibroblasts increased expression of CXCL12 downstream of increased expression of the noncanonical NF-κB transcription factor RelB. Finally, blockade of CXCL12 with AMD3100 attenuated the exaggerated fibrosis observed in Twist1-null mice. Transcriptomic analysis of 134 IPF patients revealed that low expression of Twist1 was characterized by enrichment of T cell pathways. In conclusion, loss of Twist1 in collagen-producing cells led to increased bleomycin-induced pulmonary fibrosis, which is mediated by increased expression of CXCL12. Twist1 expression is associated with dysregulation of T cells in IPF patients. Twist1 may shape the IPF phenotype and regulate inflammation in fibrotic lung injury. PMID:28179498

  1. A anestesia peridural torácica realizada com segurança no paciente anestesiado: estudo de uma série de casos

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Nunes de Bessa

    2008-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O surgimento de casos de paraplegia seguindo a inserção de cateter peridural em pacientes anestesiados levou a questionamento por parte de alguns autores, mesmo que não se confirme que a lesão tenha ocorrido porque o paciente estava anestesiado. Por esse motivo, idealizamos este estudo, que teve como objetivo avaliar a freqüência de complicações neurológicas e de surgimento de seqüelas após anestesia peridural torácica realizada com os pacientes sob anestesia geral. MÉTODO: Participaram do estudo pacientes submetidos à intervenção cirúrgica torácica no período de 16/02/2004 a 30/05/2006. Após monitoração dos sinais vitais e realização da anestesia geral, os pacientes foram colocados em decúbito lateral e realizada anestesia peridural torácica simples ou contínua. Numa ficha especial foram registradas as intercorrências, complicações e dificuldades na realização da técnica. No pós-operatório os pacientes foram acompanhados em busca de sinais e sintomas de disfunção neurológica. RESULTADOS: Foram avaliados 113 pacientes e em 108 foi inserido cateter peridural torácico. Em 45 pacientes a punção foi considerada traumática, ou seja, sangramento no local da punção e punções múltiplas. Em dois pacientes houve perfuração acidental de dura-máter. No pós-operatório imediato um paciente relatou sensação de formigamento em membros inferiores, outro paciente apresentou dormência em membro superior, desaparecendo com a retirada e tração do cateter. A punção foi única nos dois casos. Nenhum outro paciente apresentou sinais ou sintomas de alterações neurológicas. CONCLUSÕES: Nos casos estudados não houve complicação neurológica. Quando executado com bom senso e cuidados específicos o bloqueio peridural torácico pode ser realizado com segurança no paciente anestesiado.

  2. Analgesia peridural contínua: análise da eficácia, efeitos adversos e fatores de risco para ocorrência de complicações Analgesia peridural continua: análisis de la eficacia, efectos adversos y factores de riesgo para ocurrencia de complicaciones Continuous epidural analgesia: analysis of efficacy, side effects and risk factors

    Directory of Open Access Journals (Sweden)

    Leonardo Teixeira Domingues Duarte

    2004-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A analgesia promovida pela infusão peridural de anestésico local com analgésicos opióides é reconhecidamente de boa qualidade e com poucos efeitos adversos. O objetivo deste estudo foi determinar o número, formas e gravidade das complicações pós-operatórias relacionadas à analgesia peridural e à inserção do cateter peridural. MÉTODO: Foram avaliados, retrospectivamente, 469 pacientes submetidos à analgesia peridural pós-operatória entre 18/10/1999 e 18/10/2001. A analgesia peridural foi conduzida usando-se solução de bupivacaína a 0,1% com fentanil (1 a 5 µg.ml-1, iniciando-se a infusão de 3 ml.h-1. A velocidade de infusão era ajustada de acordo com a queixa álgica do paciente. Foram analisadas as seguintes variáveis: a duração da infusão peridural; a ocorrência de efeitos adversos e complicações, relacionando-os aos dados demográficos, tipo de cirurgia e posição do cateter peridural; e a qualidade da analgesia obtida com a técnica (escala analógico-visual de dor e índice de satisfação do paciente. RESULTADOS: Os cateteres peridurais permaneceram implantados uma média de 2,2 dias, variando de 6 horas a 10 dias, e o índice global de complicações relacionadas à técnica foi de 46,3%, sendo que a maioria foi de pequena magnitude, sem repercussão clínica. Destas, 13,9% estavam relacionadas diretamente ao cateter peridural (desconexão, exteriorização, dor lombar, inflamação e infecção local. Outras complicações mais comumente encontradas foram vômitos e retenção urinária. A analgesia pós-operatória foi efetiva com 97,2% dos pacientes referindo satisfação com a técnica. Pacientes sem dor ou com dor leve, no primeiro, segundo e terceiro dias de pós-operatório, constituíram, respectivamente, 80,1%, 92,8% e 93,3% da população estudada. CONCLUSÕES: A analgesia peridural contínua é efetiva e segura. As complicações ocorridas não foram consideradas graves

  3. Anestesia peridural torácica para cirurgia plástica de mama em paciente portadora de miastenia gravis: relato de caso Anestesia peridural torácica para cirugía plástica de mama en paciente portadora de miastenia gravis: relato de caso Thoracic epidural anesthesia for mammaplasty in myasthenia gravis patient: case report

    Directory of Open Access Journals (Sweden)

    Fabiano Timbó Barbosa

    2005-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A miastenia gravis é uma doença crônica, auto-imune, caracterizada pela fraqueza da musculatura esquelética em decorrência da diminuição dos receptores de acetilcolina na junção neuromuscular. O objetivo deste relato é mostrar um caso de paciente com miastenia gravis submetida a anestesia peridural torácica para cirurgia plástica de mama. RELATO DO CASO: Paciente com 51 anos, portadora de miastenia gravis foi submetida a anestesia peridural torácica com bupivacaína e fentanil. Não houve sinais de depressão respiratória. A paciente recebeu alta hospitalar após 36 horas. CONCLUSÕES: O presente caso sugere como conduta anestésica para o paciente portador de miastenia gravis a anestesia peridural como técnica única, sem a obrigatoriedade de intubação orotraqueal.JUSTIFICATIVA Y OBJETIVOS: La miastenia gravis es una enfermedad crónica, auto-inmune, caracterizada por la debilidad de la musculatura esquelética resultante de la disminución de los receptores de acetilcolina en la unión neuromuscular. El objetivo de este relato es mostrar el caso de una paciente con miastenia gravis sometida a anestesia peridural torácica para una cirugía plástica de mama. RELATO DEL CASO: Paciente del sexo femenino, 51 años, portadora de miastenia gravis fue sometida a anestesia peridural torácica con bupivacaína y fentanil. No hubo señales de depresión respiratoria. La paciente recibió alta hospitalaria después de 36 horas. CONCLUSIONES: Este actual caso sugiere como conducta anestésica para el paciente portador de miastenia gravis la anestesia peridural como única técnica, sin la obligatoriedad de intubación orotraqueal.BACKGROUND AND OBJECTIVES: Myasthenia gravis is a chronic autoimmune disease characterized by skeletal muscles weakness promoted by decreased acetylcholine receptors in the neuromuscular junction. This report aimed at describing a case of myasthenia gravis patient submitted to thoracic

  4. Effect of anti-inflammatory steroids on the activity of selected lysosomal hydrolases in serum of rats with experimental liver fibrosis.

    Science.gov (United States)

    Drózdz, M; Olczyk, K; Kucharz, E

    1983-07-01

    Liver fibrosis was produced in rats by subcutaneous injections of carbon tetrachloride. The effect of anti-inflammatory steroids (hydrocortisone, prednisone, dexamethasone) on the activity of serum lysosomal hydrolases (beta-N-acetylglucosaminidase, beta-glucosidase and alpha-mannosidase) was investigated in healthy and CCl4 poisoned rats. The marked increase of enzymatic activity in blood serum was observed in animals with CCl4-induced liver fibrosis. Quite opposite results were found in normal rats treated with glucocorticosteroids. In rats which were given both carbon tetrachloride and corticosteroids the obtained values of serum enzymatic activity did not have a uniform character as compared to controls or CCl4 intoxicated rats. Presumable mechanisms of the results obtained are discussed.

  5. How Is Cystic Fibrosis Treated?

    Science.gov (United States)

    ... Research Home / Cystic Fibrosis Cystic Fibrosis What Is Cystic fibrosis (SIS-tik fi-BRO- ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  6. How Is Cystic Fibrosis Diagnosed?

    Science.gov (United States)

    ... Research Home / Cystic Fibrosis Cystic Fibrosis What Is Cystic fibrosis (SIS-tik fi-BRO- ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  7. Simvastatin Reduces Capsular Fibrosis around Silicone Implants.

    Science.gov (United States)

    Chung, Kyu Jin; Park, Ki Rin; Lee, Jun Ho; Kim, Tae Gon; Kim, Yong-Ha

    2016-08-01

    Capsular fibrosis and contracture occurs in most breast reconstruction patients who undergo radiotherapy, and there is no definitive solution for its prevention. Simvastatin was effective at reducing fibrosis in various models. Peri-implant capsular formation is the result of tissue fibrosis development in irradiated breasts. The purpose of this study was to examine the effect of simvastatin on peri-implant fibrosis in rats. Eighteen male Sprague-Dawley rats were allocated to an experimental group (9 rats, 18 implants) or a control group (9 rats, 18 implants). Two hemispherical silicone implants, 10 mm in diameter, were inserted in subpanniculus pockets in each rat. The next day, 10-Gy of radiation from a clinical accelerator was targeted at the implants. Simvastatin (15 mg/kg/day) was administered by oral gavage in the experimental group, while animals in the control group received water. At 12 weeks post-implantation, peri-implant capsules were harvested and examined histologically and by real-time polymerase chain reaction. The average capsular thickness was 371.2 μm in the simvastatin group and 491.2 μm in the control group. The fibrosis ratio was significantly different, with 32.33% in the simvastatin group and 58.44% in the control group (P simvastatin group compared to the control group (P simvastatin reduces radiation-induced capsular fibrosis around silicone implants in rats. This finding offers an alternative therapeutic strategy for reducing capsular fibrosis and contracture after implant-based breast reconstruction.

  8. Abscesso do músculo psoas em paciente submetida à analgesia por via peridural: relato de caso Absceso del músculo psoas en paciente sometida a analgesia por vía peridural: relato del caso Psoas muscle abscess after epidural analgesia: case report

    Directory of Open Access Journals (Sweden)

    Durval Campos Kraychete

    2007-04-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O abscesso do músculo psoas é uma complicação rara da analgesia peridural. O manuseio adequado dessa intercorrência é fundamental para uma boa resolução do quadro clínico. O objetivo deste relato foi discutir o diagnóstico e o tratamento do abscesso do músculo psoas. RELATO DO CASO: Paciente do sexo feminino, 65 anos, com dor neuropática nos membros inferiores de difícil controle com medicamentos por via sistêmica. Optou-se pela administração de opióide e anestésico local por via peridural como alternativa analgésica. Vinte dias após o uso contínuo da via peridural, a paciente começou a apresentar dor na região lombar, cefaléia e febre. A tomografia computadorizada da pelve revelou abscesso do músculo psoas, sendo indicada drenagem fechada e antibioticoterapia. CONCLUSÕES: A supervisão minuciosa do paciente é necessária e deve ser contínua quando um cateter peridural for colocado. Essa vigilância deve ser mantida após a sua retirada.JUSTIFICATIVA Y OBJETIVOS: El absceso del músculo psoas es una complicación rara de la analgesia peridural. El manoseo adecuado de esa situación intercurrente es fundamental para una buena resolución del cuadro clínico. El objetivo de este relato fue discutir el diagnóstico y el tratamiento del absceso del músculo psoas. RELATO DEL CASO: Paciente del sexo femenino, 65 años, con dolor neuropático en los miembros inferiores de difícil control con medicamentos por vía sistémica. Se optó por la administración de opioide y anestésico local por vía peridural como alternativa analgésica. Veinte días después del uso continuo de la vía peridural, la paciente empezó a presentar dolor en la región lumbar, cefalea y fiebre. La tomografía computadorizada de la pelvis reveló absceso del músculo psoas, siendo indicado el drenado cerrado y antibioticoterapia. CONCLUSIONES: La supervisión minuciosa del paciente es necesaria y debe ser continua cuando

  9. Cystic fibrosis - nutritional considerations

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002437.htm Cystic fibrosis - nutrition To use the sharing features on this page, please enable JavaScript. Cystic fibrosis (CF) is a life-threatening disease that causes ...

  10. Cystic Fibrosis and Pregnancy

    Science.gov (United States)

    ... Global Map Premature Birth Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal ... complications > Cystic fibrosis and pregnancy Cystic fibrosis and pregnancy E-mail to a friend Please fill in ...

  11. Non Cirrhotic Portal Fibrosis

    OpenAIRE

    Girson, Ralph; Sanityoso, Andri; Gani, Rino A.; Marwoto, Wirasmi; Abdullah, Murdani; Syam, Ari Fahrial

    2005-01-01

    Diagnosis of non cirrhotic portal fibrosis was considered when the following criteria were fulfilled evidence of portal hypertension (oesophageal varices, hypersplenism, ascites, or increased hepatic venous pressure gradient), Doppler ultrasound showing patent portal and hepatic veins, and liver biopsy showing sign of cirrhosis. Non cirrhotic portal fibrosis clinically characterized by splenomegaly, anemia, portal hypertension, and histopathological examination portal tract showing fibrosis a...

  12. Estudo comparativo entre fentanil por vias peridural e venosa para analgesia de operações ortopédicas Estudio comparativo entre fentanil por vías peridural y venosa para analgesia de operaciones ortopédicas Comparative study of epidural and intravenous fentanyl for postoperative analgesia of orthopedic surgeries

    Directory of Open Access Journals (Sweden)

    Marcelo Soares Privado

    2004-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Existem controvérsias sobre o local de ação de opióides lipofílicos após injeção peridural, e alguns autores acreditam que esses fármacos agem no nível supra-espinhal, enquanto outros acham que ocorre ação espinhal. Para tentar esclarecer essa dúvida foi feito estudo comparativo da aplicação de fentanil por vias peridural e venosa após operações ortopédicas de membro inferior. MÉTODO: O estudo foi aleatório e duplamente encoberto. Quando apresentavam dor pós-operatória, os pacientes do G1 (n = 14 receberam 5 ml de solução (100 µg de fentanil em solução fisiológica a 0,9% por via peridural e 2 ml de solução fisiológica a 0,9% por via venosa, os do G2 (n = 15 receberam 5 ml de solução fisiológica a 0,9%, por via peridural e 2 ml de fentanil (100 µg por via venosa. Foi avaliada a necessidade de complementação analgésica com tenoxicam (40 mg por via venosa e com bupivacaína a 0,25% (5 ml por via peridural (quando não havia alívio com tenoxicam. A intensidade da dor foi avaliada pelas escalas numérica e verbal nos momentos M30, M120 e M240 minutos. RESULTADOS: O número de pacientes que necessitaram de complementação analgésica, tanto com o tenoxicam (G1 = 10 e G2 = 15 pacientes quanto com a bupivacaína (G1 = 2 e G2 = 8 pacientes foi maior no G2. Não houve diferença estatística na intensidade da dor entre os grupos nos tempos avaliados. CONCLUSÕES: Nas condições deste estudo o efeito analgésico do fentanil peridural é melhor que por via venosa.JUSTIFICATIVA Y OBJETIVOS: Existen controversias sobre el local de acción de opioides lipofílicos después de inyección peridural, y algunos autores acreditan que eses fármacos actúan en el nivel supra-espinal, en cuanto otros suponen que ocurre acción espinal. Para tentar esclarecer esa duda fue hecho estudio comparativo de la aplicación de fentanil por vías peridural y venosa después de operaciones ortopédicas de

  13. Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis primarily by insulin-dependent mechanisms in experimental type-II diabetes. Potential roles of GLP-1 isoforms.

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    Belén Picatoste

    Full Text Available BACKGROUND: Myocardial fibrosis is a key process in diabetic cardiomyopathy. However, their underlying mechanisms have not been elucidated, leading to a lack of therapy. The glucagon-like peptide-1 (GLP-1 enhancer, sitagliptin, reduces hyperglycemia but may also trigger direct effects on the heart. METHODS: Goto-Kakizaki (GK rats developed type-II diabetes and received sitagliptin, an anti-hyperglycemic drug (metformin or vehicle (n=10, each. After cardiac structure and function assessment, plasma and left ventricles were isolated for biochemical studies. Cultured cardiomyocytes and fibroblasts were used for in vitro assays. RESULTS: Untreated GK rats exhibited hyperglycemia, hyperlipidemia, plasma GLP-1 decrease, and cardiac cell-death, hypertrophy, fibrosis and prolonged deceleration time. Moreover, cardiac pro-apoptotic/necrotic, hypertrophic and fibrotic factors were up-regulated. Importantly, both sitagliptin and metformin lessened all these parameters. In cultured cardiomyocytes and cardiac fibroblasts, high-concentration of palmitate or glucose induced cell-death, hypertrophy and fibrosis. Interestingly, GLP-1 and its insulinotropic-inactive metabolite, GLP-1(9-36, alleviated these responses. In addition, despite a specific GLP-1 receptor was only detected in cardiomyocytes, GLP-1 isoforms attenuated the pro-fibrotic expression in cardiomyocytes and fibroblasts. In addition, GLP-1 receptor signalling may be linked to PPARδ activation, and metformin may also exhibit anti-apoptotic/necrotic and anti-fibrotic direct effects in cardiac cells. CONCLUSIONS: Sitagliptin, via GLP-1 stabilization, promoted cardioprotection in type-II diabetic hearts primarily by limiting hyperglycemia e hyperlipidemia. However, GLP-1 and GLP-1(9-36 promoted survival and anti-hypertrophic/fibrotic effects on cultured cardiac cells, suggesting cell-autonomous cardioprotective actions.

  14. Imaging of intestinal fibrosis: current challenges and future methods.

    Science.gov (United States)

    Stidham, Ryan W; Higgins, Peter Dr

    2016-08-01

    Crohn's disease (CD) activity assessments are dominated by inflammatory changes without discrete measurement of the coexisting fibrotic contribution to total bowel damage. Intestinal fibrosis impacts the development of severe structural complications and the overall natural history of CD. Measuring intestinal fibrosis is challenging and existing methods of disease assessment are unable to reliably distinguish fibrosis from inflammation. Both the immediate clinical need to measure fibrosis for therapeutic decision-making and the near-future need for tools to assess pipeline anti-fibrotic medications highlight the demand for biomarkers of fibrosis in CD. Developing non-invasive technologies exploit changes in intestinal perfusion, mechanical properties, and macromolecular content to provide quantitative markers of fibrosis. In this review of existing and experimental technologies for imaging intestinal fibrosis, we discuss the expanding capabilities of quantitative MR and ultrasound imaging, encouraging developments in non-invasive elastography, and emerging novel methods including photoacoustic imaging.

  15. Concentração plasmática de ropivacaína durante anestesia peridural lombar em crianças

    Directory of Open Access Journals (Sweden)

    Verônica Vieira da Costa

    2002-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A ropivacaína é o mais novo anestésico local de uso na prática clínica. Sua estrutura é semelhante a forma levógira da bupivacaína, tendo portanto baixa toxicidade. Os valores das concentrações plasmáticas que podem ser atingidos em crianças, com o uso desta droga e também da bupivacaína (mesmo a forma racêmica administradas por via peridural lombar, são ainda pouco conhecidos. O objetivo desse estudo foi avaliar as concentrações sangüíneas de ropivacaína e bupivacaína por via peridural lombar em crianças, em bloqueios eficientes, relacionando-as aos valores descritos como níveis plasmáticos seguros. MÉTODO: Oitenta e um pacientes de ambos os sexos, submetidos à cirurgia de membros inferiores, receberam aleatoriamente ropivacaína (n = 41 ou bupivacaína (n = 40 por via peridural lombar associado à anestesia geral. Foram coletadas oito amostras de sangue venoso nos intervalos de tempo: zero (controle, 5, 25, 40, 60, 120, 180 e 240 minutos, e através de cromatografia de gás foram dosadas as concentrações plasmáticas da ropivacaína e da bupivacaína. RESULTADOS: Não houve diferença estatisticamente significante com relação aos dados antropométricos e variáveis fisiológicas estudadas entre os pacientes que receberam ropivacaína e bupivacaína. As doses médias administradas de ropivacaína e bupivacaína foram 2,35 mg.kg-1 e 2,13 mg.kg-1, respectivamente, que geraram as concentrações plasmáticas de 2,334 µg.ml-1 e 1,111 µg.ml-1, aos 25 e 40 minutos. Ambas abaixo do nível considerado seguro (3 µg.kg-1. CONCLUSÕES: A administração peridural lombar de ropivacaína e bupivacaína em crianças, nas doses abaixo de 3 mg.kg-1, produz bloqueio anestésico eficaz e determina concentrações plasmáticas que podem ser consideradas seguras.

  16. Hepatic fibrosis: Concept to treatment.

    Science.gov (United States)

    Trautwein, Christian; Friedman, Scott L; Schuppan, Detlef; Pinzani, Massimo

    2015-04-01

    Understanding the molecular mechanisms underlying liver fibrogenesis is fundamentally relevant to developing new treatments that are independent of the underlying etiology. The increasing success of antiviral treatments in blocking or reversing the fibrogenic progression of chronic liver disease has unearthed vital information about the natural history of fibrosis regression, and has established important principles and targets for antifibrotic drugs. Although antifibrotic activity has been demonstrated for many compounds in vitro and in animal models, none has been thoroughly validated in the clinic or commercialized as a therapy for fibrosis. In addition, it is likely that combination therapies that affect two or more key pathogenic targets and/or pathways will be needed. To accelerate the preclinical development of these combination therapies, reliable single target validation is necessary, followed by the rational selection and systematic testing of combination approaches. Improved noninvasive tools for the assessment of fibrosis content, fibrogenesis and fibrolysis must accompany in vivo validation in experimental fibrosis models, and especially in clinical trials. The rapidly changing landscape of clinical trial design for liver disease is recognized by regulatory agencies in the United States (FDA) and Western Europe (EMA), who are working together with the broad range of stakeholders to standardize approaches to testing antifibrotic drugs in cohorts of patients with chronic liver diseases. Copyright © 2015. Published by Elsevier B.V.

  17. FIBROSIS AND LOSS OF SMOOTH MUSCLE IN THE CORPORA CAVERNOSA PRECEDE CORPORAL VENO-OCCLUSIVE DYSFUNCTION (CVOD) INDUCED BY EXPERIMENTAL CAVERNOSAL NERVE DAMAGE IN THE RAT

    Science.gov (United States)

    Ferrini, Monica G.; Kovanecz, Istvan; Sanchez, Sandra; Umeh, Chiome; Rajfer, Jacob; Gonzalez-Cadavid, Nestor F.

    2009-01-01

    Introduction Corporal veno-occlusive dysfunction (CVOD), which usually is associated with a loss of smooth muscle cells (SMC) and an increase in fibrosis within the corpora cavernosa, can be induced by an injury to the cavernosal nerves. The corporal tissue expresses inducible nitric oxide synthase (iNOS), presumably as an anti-fibrotic and SMC-protective response. Aims We studied the temporal relationship in the corpora between the expression of iNOS, other histological and biochemical changes, and the development of CVOD, after bilateral cavernosal nerve resection (BCNR) in the rat. Methods Rats underwent either BCNR or sham operation. Cavernosometry was performed 1, 3, 7, 15, 30, and 45 days (n=8/groups) after surgery. Penile tissue sections were subjected to Masson trichrome staining for SMC and collagen, and immunodetection for alpha smooth muscle actin, iNOS, neuronal NOS (nNOS), endothelial NOS (eNOS), proliferating cell nuclear antigen (PCNA), and TUNEL. Quantitative western blot analysis was done in homogenates. Main outcome measures Time course on the development of fibrosis and CVOD Results Following BCNR, CVOD was detectable 30 days later and it became more pronounced by 45 days. In contrast, the SMC/collagen ratio in the BCNR corpora was reduced at 7 days and bottomed at 30 and 45 days, due in part to the reduction of SMC, presumably caused by an increase in apoptosis peaking at 3 days. PCNA also peaked at 3 days but then decayed. nNOS was reduced early (3-7 days) and disappeared at 30 days, whereas eNOS was not affected. iNOS was induced at day 3, and steadily increased peaking at 30 days. Conclusions CVOD develops in the BCNR rat as a result of the early loss of corporal SMC by the neuropraxia-induced apoptosis, which the initial cell replication response cannot counteract, followed by fibrosis. The time course of iNOS induction supports the antifibrotic role of iNOS. PMID:19138364

  18. Analgesia preemptiva com S(+cetamina e bupivacaína peridural em histerectomia abdominal Analgesia preemptiva con S(+cetamina y bupivacaína peridural en histerectomía abdominal Preemptive analgesia with epidural bupivacaine and S(+ketamine in abdominal hysterectomy

    Directory of Open Access Journals (Sweden)

    Ferdinand Edson de Castro

    2005-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O presente estudo investiga a capacidade de o antagonista do receptor NMDA, S(+cetamina, associado à injeção peridural de anestésico local (bupivacaína, previamente administrado à incisão promover analgesia preemptiva em pacientes submetidas a histerectomia total abdominal. MÉTODO: Foram avaliadas 30 pacientes, distribuídas aleatoriamente em dois grupos de igual tamanho e estudadas prospectivamente de forma encoberta. Injeção peridural e inserção de cateter foram realizadas entre os interespaços de L1-L2. No grupo I (G1, n = 15, as pacientes receberam, por via peridural, 17 mL de bupivacaína a 0,25%, sem vasoconstritor, associados a 30 mg de S(+cetamina (3 mL, trinta minutos antes da incisão cirúrgica; após 30 minutos da incisão, receberam 20 mL de solução fisiológica a 0,9%. No grupo 2 (G2, n = 15, receberam 20 mL de solução fisiológica, por via peridural, 30 minutos antes da incisão, sendo feita administração de 17 mL de bupivacaína a 0,25% associados a 30 mg de S(+cetamina (3 mL, trinta minutos depois da incisão. Após a injeção peridural, realizou-se anestesia geral com propofol, pancurônio, O2 e isoflurano. Para analgesia pós-operatória foi usada solução peridural em bolus de fentanil associada à bupivacaína, em intervalo mínimo de quatro horas e suplementação com dipirona, se necessária. Avaliou-se a intensidade da dor através de escala numérica e verbal (ao despertar, 6, 12, 18 e 24 horas após o término da operação, o tempo necessário para solicitar pela primeira vez o analgésico e o consumo total de analgésicos. RESULTADOS: Não houve diferença significativa entre os grupos em relação ao tempo para solicitar analgésicos pela primeira vez, ao consumo de analgésicos e aos escores de dor pelas escalas numérica e verbal. CONCLUSÕES: Não foi possível demonstrar efeito preemptivo com a utilização peridural de S(+cetamina e bupivacaína nas doses

  19. Analgesia de parto: estudo comparativo entre anestesia combinada raquiperidural versus anestesia peridural contínua Analgesia de parto: estudio comparativo entre anestesia combinada raqui-peridural versus anestesia peridural continua Labor analgesia: a comparative study between combined spinal-epidural anesthesia versus continuous epidural anesthesia

    Directory of Open Access Journals (Sweden)

    Carlos Alberto de Figueiredo Côrtes

    2007-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O alívio da dor no trabalho de parto tem recebido atenção constante visando ao bem-estar materno, diminuindo o estresse causado pela dor e reduzindo as conseqüências deste sobre o concepto. Inúmeras técnicas podem ser utilizadas para analgesia de parto. Este trabalho teve como objetivo comparar a técnica peridural contínua com a combinada, ambas com o uso de bupivacaína a 0,25% em excesso enantiomérico 50% e fentanil como agentes. MÉTODO: Participaram do estudo 40 parturientes em trabalho de parto com dilatação cervical entre 4 e 5 cm que foram distribuídas em dois grupos iguais de forma aleatória. O Grupo I recebeu anestesia peridural contínua. O Grupo II recebeu anestesia combinada. Foram avaliados: medidas antropométricas, idade gestacional, dilatação cervical, tempo entre o bloqueio e a ausência de dor por meio da escala analógica visual, possibilidade de deambulação, tempo entre o início da analgesia e a dilatação cervical completa, duração do período expulsivo, parâmetros hemodinâmicos maternos e vitalidade do recém-nascido. Possíveis complicações, como depressão respiratória, hipotensão arterial materna, prurido, náuseas e vômitos, também foram observadas. Para a comparação das médias utilizou-se o teste t de Student e para a paridade e tipo de parto utilizou-se o teste do Qui-quadrado. RESULTADOS: Não houve diferença estatística significativa entre os dois grupos em relação ao tempo entre o início da analgesia e a dilatação cervical completa, bem como em relação ao tempo da duração do período expulsivo, incidência de cesariana relacionada com a analgesia, parâmetros hemodinâmicos maternos e vitalidade do recém-nascido. CONCLUSÕES: Ambas as técnicas se mostraram eficazes e seguras para a analgesia do trabalho de parto, embora a técnica combinada tenha proporcionado um rápido e imediato alívio da dor. Estudos clínicos com maior número de casos s

  20. Autophagy in Hepatic Fibrosis

    Directory of Open Access Journals (Sweden)

    Yang Song

    2014-01-01

    Full Text Available Hepatic fibrosis is a leading cause of morbidity and mortality worldwide. Hepatic fibrosis is usually associated with chronic liver diseases caused by infection, drugs, metabolic disorders, or autoimmune imbalances. Effective clinical therapies are still lacking. Autophagy is a cellular process that degrades damaged organelles or protein aggregation, which participates in many pathological processes including liver diseases. Autophagy participates in hepatic fibrosis by activating hepatic stellate cells and may participate as well through influencing other fibrogenic cells. Besides that, autophagy can induce some liver diseases to develop while it may play a protective role in hepatocellular abnormal aggregates related liver diseases and reduces fibrosis. With a better understanding of the potential effects of autophagy on hepatic fibrosis, targeting autophagy might be a novel therapeutic strategy for hepatic fibrosis in the near future.

  1. Genetics Home Reference: cystic fibrosis

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Cystic fibrosis Cystic fibrosis Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Cystic fibrosis is an inherited disease characterized by the buildup ...

  2. Fibrosis in tubularized skin flaps in rats, using silicon catheters with two different degrees of flexibility: experimental model Fibrose em retalhos tubulizados de pele de ratos usando cateteres de diferentes flexibilidades como molde: modelo experimental

    Directory of Open Access Journals (Sweden)

    Antonio Henrique Rodrigues dos Passos

    2008-06-01

    Full Text Available PURPOSE: Microscopically evaluate the intensity of fibrosis in tubularized skin flaps on the back of Wistar rats, using silicon molds with different degrees of flexibility. METHODS: Twenty rats were submitted to three tubularized skin flaps on their backs. In two tubular flaps, we placed, as a mold, silicon catheters with different degrees of flexibility and removed them on the seventh day after the surgery. They were divided into two groups and euthanized, on the seventh and twenty-first days respectively after the surgery for the collection of the pieces, coloration with Masson tricromic, quantification of the area of each sample and comparison among the groups. RESULTS: Fibrosis was less intense on the tubular flaps where a catheter was not used as a mold. No significant difference was verified among the pieces with the silicon catheters, but there was a tendency of less fibrosis on the tubules with the most flexible catheter. CONCLUSION: There was no significant difference among the two catheter types. Fibrosis was less intense in the flaps where the mold was not used.OBJETIVO: Avaliar microscopicamente a intensidade da fibrose em retalhos tubulares de pele do dorso de ratos Wistar em uso de moldes de silicone de diferentes flexibilidades. MÉTODOS: Vinte animais foram submetidos à confecção de três retalhos tubulizados de pele na região dorsal. Em dois túbulos foram colocados, como molde, cateteres de silicone com flexibilidades diferentes e retirados no sétimo dia após a cirurgia. Foram divididos em dois grupos e sacrificados, respectivamente, no sétimo e vigésimo primeiro dia após a cirurgia para a coleta das peças, coloração pelo tricrômico de Masson, quantificação da área de cada amostra e comparação entre os grupos. RESULTADOS: A fibrose foi menos intensa nos retalhos tubulares em que não se usou cateter como molde. Não se verificou diferença significativa entre os retalhos com os cateteres de silicone, mas sim

  3. Neonatal cystic fibrosis screening test

    Science.gov (United States)

    Cystic fibrosis screening - neonatal; Immunoreactive trypsinogen; IRT test; CF - screening ... Cystic fibrosis is a disease passed down through families. CF causes thick, sticky mucus to build up in ...

  4. Diagnosis of cystic fibrosis

    NARCIS (Netherlands)

    H.J. Veeze

    1995-01-01

    textabstractApplying the sweat-test as the first choice of test when a diagnosis of cystic fibrosis is suspected is still common practice and advisable. Since the cloning of the CFTR gene more than 400 different cystic fibrosis (CF) mutations have already been identified. The use of CF mutation

  5. Myocardial Fibrosis in Athletes.

    NARCIS (Netherlands)

    Schoor, F.R. van de; Aengevaeren, V.L.; Hopman, M.T.E.; Oxborough, D.L.; George, K.P.; Thompson, P.D.; Eijsvogels, T.M.H.

    2016-01-01

    Myocardial fibrosis (MF) is a common phenomenon in the late stages of diverse cardiac diseases and is a predictive factor for sudden cardiac death. Myocardial fibrosis detected by magnetic resonance imaging has also been reported in athletes. Regular exercise improves cardiovascular health, but

  6. Angiogenesis in liver fibrosis

    NARCIS (Netherlands)

    Adlia, Amirah

    2017-01-01

    Angiogenesis emerges in parallel with liver fibrosis, but it is still unclear whether angiogenesis is a defense mechanism of the body in response to fibrosis, or whether it aggravates the fibrotic condition. In this thesis, Amirah Adlia applied different approaches to elucidate the role of

  7. Modeling pulmonary fibrosis with bleomycin.

    Science.gov (United States)

    Mouratis, Marios A; Aidinis, Vassilis

    2011-09-01

    Idiopathic pulmonary fibrosis is a chronic pulmonary disease of unknown origin ultimately leading to death. No treatment exists yet and animal models have been employed in order to elucidate its etiopathogenesis. Here, we summarize the characteristics of the bleomycin animal model, the most commonly used model of pulmonary fibrosis, highlighting recent advances it has led us to despite its disadvantages. Repetitive intratracheal administration of bleomycin more effectively mimics the chronic aspect of pulmonary fibrosis, as well as other characteristics including the presence of hyperplastic alveolar epithelial cells. Epithelial-to-mesenchymal transition seems to be a major contributor to the lung fibroblast population. There is growing evidence that macrophages, as well as fibrocytes, are largely involved in disease progression by mediating fibroblast and myofibroblast activation. In addition, molecules involved in phospholipid homeostasis are now becoming more appealing as potential therapeutic targets. Despite its disadvantages, the bleomycin animal model remains the best available experimental tool for studying disease pathogenesis and testing of novel pharmaceutical compounds. Two such compounds currently showing some promise in clinical trials have emerged through the bleomycin model and preliminary results of basic research using this model have shown that more candidate compounds may follow in the near future.

  8. Galectin-3 Regulates Myofibroblast Activation and Hepatic Fibrosis

    National Research Council Canada - National Science Library

    Neil C. Henderson; Alison C. Mackinnon; Sarah L. Farnworth; Francoise Poirier; Francesco P. Russo; John P. Iredale; Christopher Haslett; Kenneth J. Simpson; Tariq Sethi

    2006-01-01

    .... We demonstrate that Galectin-3 expression is up-regulated in established human fibrotic liver disease and is temporally and spatially related to the induction and resolution of experimental hepatic fibrosis...

  9. Lumbociatalgia: comparación de la analgesia entre metilprednisolona, fentanil y metilprednisolona con fentanil, asociados a la bupivacaína, por vía peridural

    OpenAIRE

    Rocha, Quitéria Maria Wanderley [UNIFESP; Sakata, Rioko Kimiko [UNIFESP; Issy, Adriana Machado [UNIFESP

    2001-01-01

    JUSTIFICATIVA E OBJETIVOS: Os corticosteróides têm sido empregados no espaço peridural, como alternativa de tratamento da lombalgia refratária às medidas conservadoras. Os opióides têm efeito analgésico através da ligação a receptores da medula espinhal e poderiam ter efeito somatório. Este estudo teve como objetivo avaliar a eficácia, os efeitos colaterais e as complicações de opióide e corticosteróide associados ao anestésico local, para tratamento da lombalgia e lombociatalgia aguda, provo...

  10. Anestesia peridural contínua para cesariana em paciente com arterite de Takayasu: relato de caso Anestesia peridural continua para cesárea en paciente con arteritis de Takayasu: relato de caso Continuous epidural anesthesia for cesarean section in a patient with Takayasu’s arteritis: case report

    Directory of Open Access Journals (Sweden)

    Aloísio Cerqueira Buettel

    2002-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Anestesia peridural contínua com titulação das doses de anestésico local proporciona eficácia e segurança em pacientes que não toleram flutuações da pressão arterial. O objetivo deste relato é apresentar um caso em que foi utilizada com sucesso anestesia peridural contínua para cesariana em paciente com arterite de Takayasu. RELATO DO CASO: Paciente primigesta, 25 anos, 63 kg, portadora de arterite de Takayasu, com 34-35 semanas de gestação, apresentando sofrimento fetal agudo, PA de 155/85 mmHg, FC de 92 bpm, com ausência de pulsos carotídeos, assim como nos membros superiores e do membro inferior direito. Apresentava apenas pulso poplíteo esquerdo palpável. Foi realizado bloqueio peridural contínuo com doses fracionadas de 25 mg de bupivacaína a 0,5% com epinefrina (1:200.000, a intervalos de 5 em 5 minutos até um total de 100 mg, associando-se 2 mg de morfina e 100 µg de fentanil. CONCLUSÕES: A anestesia peridural contínua com doses tituladas de bupivacaína a 0,5% com epinefrina pode ser utilizada em pacientes com Arterite de Takayasu, tomando-se as medidas de precaução com portadoras dessa doença.JUSTIFICATIVA Y OBJETIVOS: Anestesia peridural continua con titulación de las dosis de anestésico local proporciona eficacia y seguridad en pacientes que no toleran flutuaciones de la presión arterial. El objetivo de este relato es presentar un caso en que fue utilizado con suceso anestesia peridural continua para cesárea en paciente con arteritis de Takayasu. RELATO DEL CASO: Paciente primigesta, 25 años, 63 kg, portadora de Arteritis de Takayasu, con 34-35 semanas de gestación, presentando sufrimiento fetal agudo, PA de 155/85 mmHg, FC de 92 bpm, con ausencia de pulsos carotídeos, así como en los miembros superiores y del miembro inferior derecho. Presentaba apenas pulso poplíteo izquierdo palpable. Fue realizado bloqueo peridural continuo con dosis fraccionadas de 25 mg de bupivaca

  11. Learning about Cystic Fibrosis

    Science.gov (United States)

    Skip to main content Learning About Cystic Fibrosis Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research News Features Funding Divisions Funding ...

  12. Fibrosis and Cancer

    DEFF Research Database (Denmark)

    Cox, Thomas R.; Erler, Janine T.

    2016-01-01

    The relation between fibrosis and cancer has long been debated, specifically whether desmoplasia precedes, accompanies, or succeeds tumourigenesis, progression, and metastasis. Recent reports have published opposing data, adding to the perplexity. However, what is emerging is that it is likely...

  13. Markers of hepatic fibrosis.

    Science.gov (United States)

    Caballería, Llorenç; Torán, Pere; Caballería, Joan

    2017-10-18

    Chronic liver diseases constitute a major health problem. Chronic liver inflammation, defined by the degree of hepatic fibrosis, is asymptomatic in a significant percentage of patients; hence, the disease often remains undiagnosed until it has reached very advanced phases and, frequently, when the damage is irreversible. Ideally, patients should be screened during the initial phases of chronic inflammation, thus allowing for the effective management of the natural evolution of the disease by stopping or delaying its course. Standard diagnostic methods (transaminase determination or abdominal ultrasonography) do not allow for the early diagnosis of the degree of fibrosis. A liver biopsy is the invasive method of choice to screen for fibrosis, however, due to its limitations, non-invasive diagnostic methods such as elastography or serological markers are increasingly used as a good alternative for the early diagnosis of the degree of fibrosis. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  14. About Cystic Fibrosis

    Science.gov (United States)

    ... AWARENESS Tomorrow’s Leaders About Us News Blog Chapters Facebook Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home What Is CF About Cystic Fibrosis Share Facebook Twitter Email More options Print Share Facebook Twitter ...

  15. Incidência de depressão respiratória no pós-operatório em pacientes submetidos à analgesia venosa ou peridural com opioides

    OpenAIRE

    Duarte,Leonardo Teixeira Domingues; Fernandes,Maria do Carmo Barretto de Carvalho; Costa,Verônica Vieira da; Saraiva,Renato Ângelo

    2009-01-01

    JUSTIFICATIVA E OBJETIVOS: A analgesia controlada pelo paciente (PCA), por via venosa ou peridural, é técnica segura e eficaz no tratamento da dor pós-operatória. Todavia, o uso de opioides não é isento de risco, e a depressão respiratória é a complicação mais temida. Os objetivos deste estudo foram descrever a incidência de depressão respiratória associada à analgesia pós-operatória com opioides administrados por via peridural ou venosa e as características dos pacientes que apresentaram a c...

  16. Development and time-course of bleomycin-induced pulmonary fibrosis in NMRI mice

    Directory of Open Access Journals (Sweden)

    Jafarian-Dehkordi A.

    2007-04-01

    Full Text Available Bleomycin-induced pulmonary fibrosis is a widely used experimental model for human lung fibrosis. The severity of fibrosis varies among different strains of mice and investigation on different strains and finding the mechanisms of variation is important in understanding the pathogenesis of human lung fibrosis. In the present study, NMRI mice were used to investigate the severity and also time-course of bleomycin-induced pulmonary fibrosis in comparison with C57BL/6 mice. After single dose administration of intratracheal bleomycin, the fibrotic response was studied by biochemical measurement of collagen deposition and semiquantitative analysis of pathological lung changes. NMRI mice developed lung fibrosis from 1 to 4 week after bleomycin instillation, with significant increases in lung collagen content and significant morphological changes (P < 0.05. These findings indicate that NMRI mice might be suitable as an experimental model of bleomycin-induced lung fibrosis.

  17. Fibrosis with emphysema.

    Science.gov (United States)

    Wright, Joanne L; Tazelaar, Henry D; Churg, Andrew

    2011-03-01

    The concept of fibrosis with emphysema is confused by the existence of two very different clinical/pathological scenarios: first, cases in which a diffuse fibrosing interstitial pneumonia, most commonly usual interstitial pneumonia (UIP), occurs in a patient with emphysema. This combination is largely of clinical interest because of its effects on pulmonary function and pulmonary hypertension, but can produce unusual appearances in surgical lung biopsies when the fibrotic areas are wrapped around emphysematous spaces. However, the underlying morphology of emphysema and UIP or other interstitial lung disease remains unchanged. Radiological consultation is often helpful to show that the patient has both lesions; secondly, cases in which there is localized fibrosis that is part of emphysema, or related to respiratory bronchiolitis, or both. These lesions have been called 'respiratory bronchiolitis' (RB), 'respiratory bronchiolitis-interstitial lung disease' (RB-ILD), 'airspace enlargement with fibrosis', 'RB-ILD with fibrosis' and 'clinically occult interstitial fibrosis in smokers', but are probably all the same entity. Such changes are associated only rarely with the physiological or radiological features of an interstitial lung disease. Care should be taken when describing these lesions in biopsies so as not to give the impression that a diffuse interstitial lung disease is present. © 2010 Blackwell Publishing Limited.

  18. Alveolar inflammation in cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Worlitzsch, Dieter; Viglio, Simona

    2010-01-01

    BACKGROUND: In infected lungs of the cystic fibrosis (CF) patients, opportunistic pathogens and mutated cystic fibrosis transmembrane conductance regulator protein (CFTR) contribute to chronic airway inflammation that is characterized by neutrophil/macrophage infiltration, cytokine release and ce...

  19. Optical methods in diagnostics of liver fibrosis via blood observation

    Science.gov (United States)

    Kruchinina, Margarita V.; Generalov, Vladimir M.; Atuchin, Victor V.; Kruchinin, Vladimir N.; Volodin, Vladimir A.; Gromov, Andrey A.; Rykhlitsky, Sergey V.

    2016-11-01

    A possible application of optical methods (dielectrophoresis, spectral and imaging ellipsometry, Fourier- transform infrared spectroscopy, Raman spectroscopy) for the early diagnostics in studies of red blood cells and serum in patients with the diffuse liver disease, with varying degrees of fibrosis, has been evaluated. As experimentally confirmed, the combined optical methods significantly improve the sensitivity, specificity and accuracy index in the diagnosis of both severe fibrosis and slight ulterior liver fibrosis. The identified optical methods diagnostic potential can be efficiently utilized in noninvasive screening evaluation of the stages of diffuse liver disease of various genesis.

  20. Mechanotransduction and fibrosis.

    Science.gov (United States)

    Duscher, Dominik; Maan, Zeshaan N; Wong, Victor W; Rennert, Robert C; Januszyk, Michael; Rodrigues, Melanie; Hu, Michael; Whitmore, Arnetha J; Whittam, Alexander J; Longaker, Michael T; Gurtner, Geoffrey C

    2014-06-27

    Scarring and tissue fibrosis represent a significant source of morbidity in the United States. Despite considerable research focused on elucidating the mechanisms underlying cutaneous scar formation, effective clinical therapies are still in the early stages of development. A thorough understanding of the various signaling pathways involved is essential to formulate strategies to combat fibrosis and scarring. While initial efforts focused primarily on the biochemical mechanisms involved in scar formation, more recent research has revealed a central role for mechanical forces in modulating these pathways. Mechanotransduction, which refers to the mechanisms by which mechanical forces are converted to biochemical stimuli, has been closely linked to inflammation and fibrosis and is believed to play a critical role in scarring. This review provides an overview of our current understanding of the mechanisms underlying scar formation, with an emphasis on the relationship between mechanotransduction pathways and their therapeutic implications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation.

    Science.gov (United States)

    Cheng, Tao; Liu, Qingbo; Zhang, Rui; Zhang, Ying; Chen, Jianfeng; Yu, Ronghuan; Ge, Gaoxiang

    2014-12-01

    Enzymes involved in collagen biosynthesis, including lysyl oxidase (LOX), have been proposed as potential therapeutic targets for idiopathic pulmonary fibrosis. LOX expression is significantly upregulated in bleomycin (BLM)-induced lung fibrosis, and knockdown of LOX expression or inhibition of LOX activity alleviates the lung fibrosis. Unexpectedly, treatment of the mice with LOX inhibitor at the inflammatory stage, but not the fibrogenic stage, efficiently reduces collagen deposition and normalizes lung architecture. Inhibition of LOX impairs inflammatory cell infiltration, TGF-β signaling, and myofibroblast accumulation. Furthermore, ectopic expression of LOX sensitizes the fibrosis-resistant Balb/c mice to BLM-induced inflammation and lung fibrosis. These results suggest that LOX is indispensable for the progression of BLM-induced experimental lung fibrosis by aggravating the inflammatory response and subsequent fibrosis process after lung injury. © The Author (2014). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

  2. Clonidina e dexmedetomidina por via peridural para analgesia e sedação pós-operatória de colecistectomia Clonidina y dexmedetomidina por vía peridural para analgesia y sedación pós-operatoria de colecistectomía Epidural clonidine or dexmedetomidine for post-cholecystectomy analgesia and sedation

    Directory of Open Access Journals (Sweden)

    Antônio Mauro Vieira

    2004-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A clonidina e a dexmedetomidina são agonistas alfa2-adrenérgicos que, quando administrados por via peridural, possuem propriedades analgésicas e potencializam os efeitos dos anestésicos locais. A presente pesquisa objetivou avaliar a analgesia e a sedação produzidas pela clonidina ou dexmedetomidina associadas à ropivacaína, por via peridural, no pós-operatório de colecistectomia por via subcostal. MÉTODO: Participaram do estudo aleatório e duplamente encoberto 40 pacientes, de ambos os sexos, com idade variando de 18 a 50 anos, peso entre 50 e 100 kg, estado físico ASA I e II, submetidos à colecistectomia por via subcostal, os quais foram distribuídos em dois grupos: clonidina (GC, em que foi administrada clonidina (1 ml = 150 µg associada à ropivacaína a 0,75% (20 ml por via peridural; dexmedetomidina (GD, em que foi injetada dexmedetomidina (2 µg.kg-1 associada à ropivacaína a 0,75% (20 ml por via peridural. A analgesia e a sedação foram observadas 2, 6 e 24 horas após o término da anestesia. RESULTADOS: Ocorreu sedação depois de 2 e 6 horas em ambos os grupos, sendo que houve diferença estatística significante entre os tempos de 2 e 6 horas no grupo dexmedetomidina. Houve analgesia em ambos os grupos, especialmente depois de 2 e 6 horas. Foi detectada diferença estatística significante entre os tempos de 2, 6 e 24 horas no grupo dexmedetomidina; no grupo clonidina essa diferença estatística significante foi observada entre os tempos de 2 e 6 horas e entre 2 e 24 horas. CONCLUSÕES: Os resultados permitiram concluir que a clonidina ou a dexmedetomidina associadas à ropivacaína a 0,75% asseguraram analgesia e sedação nos tempos de observação de 2 e 6 horas após o término da anestesia, nos pacientes submetidos à colecistectomia por via subcostal e que a clonidina promove analgesia mais prolongada.JUSTIFICATIVA Y OBJETIVOS: La clonidina y la dexmedetomidina son agonistas alfa2

  3. Adipose tissue fibrosis.

    Science.gov (United States)

    Buechler, Christa; Krautbauer, Sabrina; Eisinger, Kristina

    2015-05-15

    The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion of adipose tissue in obesity is linked to an inappropriate supply with oxygen and hypoxia development. Subsequent activation of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and initiates adipose tissue fibrosis. Thereby adipose tissue growth is limited and excess triglycerides are stored in ectopic tissues. Stressed adipocytes and hypoxia contribute to immune cell immigration and activation which further aggravates adipose tissue fibrosis. There is substantial evidence that adipose tissue fibrosis is linked to metabolic dysfunction, both in rodent models and in the clinical setting. Peroxisome proliferator activated receptor gamma agonists and adiponectin both reduce adipose tissue fibrosis, inflammation and insulin resistance. Current knowledge suggests that antifibrotic drugs, increasing adipose tissue oxygen supply or HIF-1 antagonists will improve adipose tissue function and thereby ameliorate metabolic diseases.

  4. Nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Khurram, Misbah; Skov, Lone; Rossen, Kristian

    2007-01-01

    Nephrogenic systemic fibrosis (NSF) is a fibrotic disease seen in renal failure patients that may lead to severe physical disability. It has been demonstrated in recent studies that NSF can be caused by some gadolinium-containing MRI contrast agents. In this report we present one of a total of 26...

  5. Nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Marckmann, Peter

    2008-01-01

    PURPOSE OF REVIEW: The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. RECENT FINDINGS: Epidemiological and histochemical studies demonstrated that gado...

  6. Pharmacological Targeting of Protease-Activated Receptor 2 Affords Protection from Bleomycin-Induced Pulmonary Fibrosis

    Science.gov (United States)

    Lin, Cong; von der Thüsen, Jan; Daalhuisen, Joost; ten Brink, Marieke; Crestani, Bruno; van der Poll, Tom; Borensztajn, Keren; Spek, C Arnold

    2015-01-01

    Idiopathic pulmonary fibrosis is the most devastating diffuse fibrosing lung disease that remains refractory to therapy. Despite increasing evidence that protease-activated receptor 2 (PAR-2) contributes to fibrosis, its importance in pulmonary fibrosis is under debate. We addressed whether PAR-2 deficiency persistently reduces bleomycin-induced pulmonary fibrosis or merely delays disease progression and whether pharmacological PAR-2 inhibition limits experimental pulmonary fibrosis. Bleomycin was instilled intranasally into wild-type or PAR-2–deficient mice in the presence/absence of a specific PAR-2 antagonist (P2pal-18S). Pulmonary fibrosis was consistently reduced in PAR-2–deficient mice throughout the fibrotic phase, as evident from reduced Ashcroft scores (29%) and hydroxyproline levels (26%) at d 28. Moreover, P2pal-18S inhibited PAR-2–induced profibrotic responses in both murine and primary human pulmonary fibroblasts (p bleomycin-treated wild-type mice but did not further reduce fibrosis in PAR-2–deficient mice. Importantly, P2pal-18S treatment starting even 7 d after the onset of fibrosis limits pulmonary fibrosis as effectively as when treatment was started together with bleomycin instillation. Overall, PAR-2 contributes to the progression of pulmonary fibrosis, and targeting PAR-2 may be a promising therapeutic strategy for treating pulmonary fibrosis. PMID:26147947

  7. Gene Expression Patterns Associated With Histopathology in Toxic Liver Fibrosis.

    Science.gov (United States)

    Ippolito, Danielle L; AbdulHameed, Mohamed Diwan M; Tawa, Gregory J; Baer, Christine E; Permenter, Matthew G; McDyre, Bonna C; Dennis, William E; Boyle, Molly H; Hobbs, Cheryl A; Streicker, Michael A; Snowden, Bobbi S; Lewis, John A; Wallqvist, Anders; Stallings, Jonathan D

    2016-01-01

    Toxic industrial chemicals induce liver injury, which is difficult to diagnose without invasive procedures. Identifying indicators of end organ injury can complement exposure-based assays and improve predictive power. A multiplexed approach was used to experimentally evaluate a panel of 67 genes predicted to be associated with the fibrosis pathology by computationally mining DrugMatrix, a publicly available repository of gene microarray data. Five-day oral gavage studies in male Sprague Dawley rats dosed with varying concentrations of 3 fibrogenic compounds (allyl alcohol, carbon tetrachloride, and 4,4'-methylenedianiline) and 2 nonfibrogenic compounds (bromobenzene and dexamethasone) were conducted. Fibrosis was definitively diagnosed by histopathology. The 67-plex gene panel accurately diagnosed fibrosis in both microarray and multiplexed-gene expression assays. Necrosis and inflammatory infiltration were comorbid with fibrosis. ANOVA with contrasts identified that 51 of the 67 predicted genes were significantly associated with the fibrosis phenotype, with 24 of these specific to fibrosis alone. The protein product of the gene most strongly correlated with the fibrosis phenotype PCOLCE (Procollagen C-Endopeptidase Enhancer) was dose-dependently elevated in plasma from animals administered fibrogenic chemicals (P liver injury and may suggest bridging biomarkers for molecular mediators linked to histopathology. Published by Oxford University Press on behalf of the Society of Toxicology 2015. This work is written by US Government employees and is in the public domain in the US.

  8. Monocyte Subsets in Schistosomiasis Patients with Periportal Fibrosis

    Directory of Open Access Journals (Sweden)

    Jamille Souza Fernandes

    2014-01-01

    Full Text Available A major issue with Schistosoma mansoni infection is the development of periportal fibrosis, which is predominantly caused by the host immune response to egg antigens. Experimental studies have pointed to the participation of monocytes in the pathogenesis of liver fibrosis. The aim of this study was to characterize the subsets of monocytes in individuals with different degrees of periportal fibrosis secondary to schistosomiasis. Monocytes were classified into classical (CD14++CD16−, intermediate (CD14++CD16+, and nonclassical (CD14+CD16++. The expressions of monocyte markers and cytokines were assessed using flow cytometry. The frequency of classical monocytes was higher than the other subsets. The expression of HLA-DR, IL-6, TNF-α, and TGF-β was higher in monocytes from individuals with moderate to severe fibrosis as compared to other groups. Although no differences were observed in receptors expression (IL-4R and IL-10R between groups of patients, the expression of IL-12 was lower in monocytes from individuals with moderate to severe fibrosis, suggesting a protective role of this cytokine in the development of fibrosis. Our data support the hypothesis that the three different monocyte populations participate in the immunopathogenesis of periportal fibrosis, since they express high levels of proinflammatory and profibrotic cytokines and low levels of regulatory markers.

  9. Unusual presence of the immune evasion gene cluster in livestock-associated MRSA of lineage CC398 causing peridural and psoas abscesses in a poultry farmer.

    Science.gov (United States)

    Pérez-Moreno, Mar Olga; Centelles-Serrano, María José; Nogales-López, Julio; Domenech-Spanedda, Marie France; Lozano, Carmen; Torres, Carmen

    2017-12-01

    To characterize a methicillin-resistant Staphylococcus aureus (MRSA) isolate responsible for an aggressive infection (peridural and psoas abscess secondary to haematogenous septic arthritis) in a poultry farmer. Molecular characterization was performed, including spa- and multilocus sequence typing of the isolate, assessment of its resistance phenotype and detection of tetracycline resistance and of virulence and immune evasion cluster (IEC) genes were performed. The MRSA isolate was tetracycline- and fluorquinolone-resistant, and was ascribed to CC398, spa-t1451. The isolate harboured tet(M) (distinctive of livestock-associated (LA) MRSA-CC398 clade) and IEC-type B system (characteristic of the methicillin-susceptible human lineage, but typically absent in LA-MRSA-CC398 strains), and lacked toxin-coding genes lukF/lukS-PV, tsst-1, eta and etb. IEC re-acquisition by LA-MRSA-CC398-LA strains is an unusual finding, but could constitute an emerging public health problem. It would represent an evolutionary step towards LA-MRSA-CC398's adaptation to human hosts, and might enhance its invasiveness and ability to be transmitted to humans. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  10. Efeitos hemodinâmicos e renais da injeção de doses elevadas de clonidina no espaço peridural do cão Efectos hemodinámicos y renales de la inyección de dosis elevadas de clonidina en el espacio peridural del perro Hemodynamic and renal effects of high epidural clonidine doses in dogs

    Directory of Open Access Journals (Sweden)

    Nilson Camargo Roso

    2005-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Não existem estudos que relatem as repercussões renais determinadas pela injeção de doses elevadas de clonidina no espaço peridural. O objetivo do estudo foi avaliar os efeitos hemodinâmicos e renais determinados pela injeção de doses elevadas de clonidina no espaço peridural do cão. MÉTODO: Vinte animais anestesiados com tiopental sódico e fentanil foram distribuídos aleatoriamente e de forma duplamente encoberta em dois grupos: Grupo 1 ou placebo (n = 10, que recebeu 0,2 mL.kg-1 de solução fisiológica, e Grupo 2 ou clonidina (n = 10, que recebeu 0,2 mL.kg-1 de uma solução contendo 50 µg.mL-1 de clonidina, no espaço peridural. Foram avaliados os seguintes parâmetros hemodinâmicos: freqüência cardíaca (FC: bat.min-1; pressão arterial média (PAM: mmHg; pressão da artéria pulmonar ocluida (PAOP: mmHg; débito cardíaco (DC: L.min-1; volume sistólico (VS: mL; também, os seguintes parâmetros da função renal foram avaliados: fluxo sangüíneo renal (FSR: mL.min-1; resistência vascular renal (RVR: mmHg.mL-1.min; volume urinário minuto (VUM: mL.min-1; depuração de creatinina (D Cr: mL.min-1; depuração de para-aminohipurato (D PAH: mL.min-1; fração de filtração (FF; depuração de sódio (D Na: mL.min-1; depuração de potássio (D K: mL.min-1; excreção fracionária de sódio (EF Na: %; excreção urinária de sódio (U NaV: µEq.min-1; excreção urinária de potássio (U K V: µEq.min-1. O experimento consistiu em três momentos de 20 minutos cada. Os dados foram coletados aos 10 minutos de cada momento e a diurese, no início e no final de cada momento. Ao término de M1, a clonidina ou a solução fisiológica foi administrada no espaço peridural. Após período de 20 minutos iniciou-se M2 e, em seguida, M3. RESULTADOS: A clonidina na dose de 10 µg.kg-1 no espaço peridural do cão promoveu alterações significativas, com diminuições da freqüência cardíaca e do d

  11. Uso do bloqueio combinado raqui-peridural durante cirurgia de cólon em paciente de alto risco: relato de caso Uso del bloqueo combinado raquiepidural durante cirugía de colon en paciente de alto riesgo: relato de caso Combined spinal epidural anesthesia during colon surgery in a high-risk patient: case report

    OpenAIRE

    Luiz Eduardo Imbelloni; Marcos Fornasari; José Carlos Fialho

    2009-01-01

    JUSTIFICATIVA E OBJETIVOS: O bloqueio combinado raqui-peridural (BCRP) oferece vantagens sobre a anestesia peridural ou subaracnóidea com injeção única. O objetivo deste relato foi apresentar um caso onde a anestesia subaracnóidea segmentar pode ser técnica efetiva para intervenção cirúrgica gastrintestinal com respiração espontânea. RELATO DO CASO: Paciente estado físico ASA III, diabetes mellitus tipo II, com hipertensão arterial sistêmica e doença pulmonar obstrutiva crônica, foi escalada ...

  12. [Cystic fibrosis: nutritional considerations].

    Science.gov (United States)

    Molina Arias, M; Prieto Bozano, G; Sarría Osés, J; Polanco Allué, I

    2001-06-01

    During the last few decades, improved treatment measures and nutritional support in cystic fibrosis have increased survival and quality of life in these patients. There is a clear relationship between the development of malnutrition and worsening in respiratory function and both factors have been related to poor disease outcome. Malnutrition is a very frequent complication of this disease and is found in 20% of patients, due to negative energy-proteic balance. This disequilibrium can be explained by increased energy expenditure, high nutritional requirements and decreased oral intake. Periodic monitoring of clinical, anthropometrical and functional nutritional status is mandatory. Intake must be greater than requirements and specific nutritional support should be established when required. Patients with cystic fibrosis must receive a hypercaloric and hyperproteotic diet, with a high fat content, a normal quantity of carbohydrates and with pancreatic and liposoluble vitamin supplements in case of pancreatic insufficiency.

  13. Adipose tissue fibrosis

    OpenAIRE

    Buechler, Christa; Krautbauer, Sabrina; Eisinger, Kristina

    2015-01-01

    The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion of adipose tissue in obesity is linked to an inappropriate supply with oxygen and hypoxia development. Subsequent activation of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and initiates adipose tissue fibrosis. The...

  14. Cystic fibrosis revisited.

    Science.gov (United States)

    Larson, J E; Cohen, J C

    2000-11-01

    Cystic fibrosis is a pleiotropic disease whose primary defect is thought to be abnormal chloride conductance. Despite intensive study, the role of the protein in the airway and the mechanism for its direct participation in the disease pathology remain unclear. This paper reviews CFTR's cell regulatory functions and data supporting the role of CFTR in secretory epithelial cell development. A hypothesis for CF pathophysiology based on secretory cell differentiation is proposed. Copyright 2000 Academic Press.

  15. EXTRAMACULAR FIBROSIS IN COATS' DISEASE.

    Science.gov (United States)

    Daruich, Alejandra; Matet, Alexandre; Tran, Hoai V; Gaillard, Marie-Claire; Munier, Francis L

    2016-10-01

    To determine the rate, risk factors, and outcome of extramacular fibrosis in Coats' disease. Consecutive cases from a single center were retrospectively reviewed. Clinical characteristics and treatments were analyzed by comparative, multivariate, and survival approaches. Among 69 patients with Coats' disease, 28 (40.6%) showed evidence of extramacular fibrosis (mean follow-up: 58.2 months). Mean time of fibrosis onset was 17.4 months. Extent of retinal exudation and rate of exudative retinal detachment at baseline were significantly higher in eyes that developed extramacular fibrosis compared with those that did not (P < 0.001). Similarly, these parameters showed significant differences using multivariate (P < 0.05) and survival analysis (P < 0.001). Extension of telangiectasia, number of cryotherapy, or laser sessions, and treatment by anti-vascular endothelial growth factor were not associated with extramacular fibrosis. Final visual acuity was worse in patients with extramacular fibrosis (P < 0.001). The rates of tractional retinal detachment and macular fibrosis were higher in patients with extramacular fibrosis (39%.0 vs. 0% and 60.7% vs. 19.5%, respectively, P < 0.001). Extramacular fibrosis led to a worse visual prognosis and was associated with the extension of retinal exudation and the presence of exudative retinal detachment at diagnosis. Treatment should target a quick resolution of exudation to limit its development.

  16. Murine models of pulmonary fibrosis

    National Research Council Canada - National Science Library

    Bethany B. Moore; Cory M. Hogaboam

    Human pulmonary fibrosis is characterized by alveolar epithelial cell injury, areas of type II cell hyperplasia, accumulation of fibroblasts and myofibroblasts, and the deposition of extracellular matrix proteins...

  17. Genetics Home Reference: idiopathic pulmonary fibrosis

    Science.gov (United States)

    ... Twitter Home Health Conditions Idiopathic pulmonary fibrosis Idiopathic pulmonary fibrosis Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Idiopathic pulmonary fibrosis is a chronic, progressive lung disease. This condition ...

  18. MicroRNAs in renal fibrosis

    Directory of Open Access Journals (Sweden)

    Arthur Chi-Kong Chung

    2015-02-01

    Full Text Available MicroRNAs (miRNAs are endogenous short noncoding RNAs that regulate most of important cellular processes by inhibiting gene expression through the post-transcriptional repression of their target mRNAs. . In kidneys, miRNAs have been associated in renal development, homeostasis, and physiological functions. Results from clinical and experimental animal studies demonstrate that miRNAs play essential roles in the pathogenesis of various renal diseases. Chronic kidney diseases (CKD is characterized by renal fibrosis. Transforming growth factor beta (TGF-β is recognized as a major mediator of renal fibrosis because it is able to stimulate the accumulation of extracellular matrix proteins to impair normal kidney function. Recently, emerging evidence demonstrate the relationship between TGF-β signaling and miRNAs expression during renal diseases. TGF-β regulates expression of several microRNAs, such as miR-21, miR-192, miR-200, miR-433, and miR-29. MiR-21, miR-192, and miR-433 which are positively induced by TGF-β signaling play a pathological role in kidney diseases. In contrast, members in both miR-29 and miR-200 families which are inhibited by TGF-β signaling protect kidneys from renal fibrosis by suppressing the deposition of extracellular matrix and preventing epithelial-to-mesenchymal transition, respectively. Clinically, the presence of miRNAs in blood and urine has been examined to be early biomarkers for detecting renal diseases. From experimental animal studies of CKD, targeting microRNAs also provides evidence about therapeutic potential of miRNAs during renal diseases. Now, it comes to the stage to examine the exact mechanisms of miRNAs during the initiation and progression of renal diseases. Therefore, determining the function of miRNAs in renal fibrosis may facilitate the development of both early diagnosis and treatment of renal diseases.

  19. Lombociatalgia: comparação da analgesia entre metilprednisolona, fentanil e metilprednisolona com fentanil, associados à bupivacaína, por via peridural

    Directory of Open Access Journals (Sweden)

    Quitéria Maria Wanderley Rocha

    2001-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Os corticosteróides têm sido empregados no espaço peridural, como alternativa de tratamento da lombalgia refratária às medidas conservadoras. Os opióides têm efeito analgésico através da ligação a receptores da medula espinhal e poderiam ter efeito somatório. Este estudo teve como objetivo avaliar a eficácia, os efeitos colaterais e as complicações de opióide e corticosteróide associados ao anestésico local, para tratamento da lombalgia e lombociatalgia aguda, provocadas por hérnia de disco. MÉTODO: Foram avaliados 45 pacientes adultos portadores de hérnia de disco. O grupo G-I recebeu 8 ml de bupivacaína a 0,25% com metilprednisolona (80 mg; o grupo G-II, 8 ml de bupivacaína a 0,25% com fentanil (100 µg e o grupo G-III, 6 ml de bupivacaína a 0,25% com fentanil (100 µg e metilprednisolona (80 mg. Havendo necessidade de repetição, nova injeção foi feita após 1 semana e 2 semanas no espaço intervertebral, ou próximo ao da localização da hérnia de disco. O efeito analgésico foi mensurado através de escala verbal. RESULTADOS: Aos 30 minutos, 6, 12 e 24 horas após o procedimento não houve diferença entre os grupos quanto ao alívio da dor. No quarto, sétimo e 14º dias, os grupos GI e GIII mostraram melhor alívio da dor, não havendo diferença estatística entre esses grupos. No grupo GII houve maior necessidade para repetir a injeção no 7º dia (GI= 33,3%; GII= 100% e GIII= 33,3%, e no 14º dia (GI= 6,6%; GII= 86,6% e GIII= 6,6%. A utilização de tramadol foi maior no GII. No GI, houve cefaléia (1 paciente; no GII, sonolência (2 pacientes e prurido (1 paciente e no GIII, prurido (1 paciente e sonolência (1 paciente. CONCLUSÕES: O citrato de fentanil não tem efeito duradouro no controle da dor da hérnia de disco e não melhora o efeito analgésico quando associado a bupivacaína e metilprednisolona por via peridural.

  20. Ropivacaína em bloqueio peridural torácico para cirurgia plástica Ropivacaína en bloqueo peridural torácico para cirugía plástica Thoracic epidural anesthesia with ropivacaine for plastic surgery

    Directory of Open Access Journals (Sweden)

    José Roberto Nociti

    2002-04-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O bloqueio peridural torácico constitui técnica de anestesia hipotensiva, capaz de reduzir o sangramento no campo operatório. O presente estudo não-comparativo tem por finalidade observar os resultados do bloqueio peridural torácico com ropivacaína a 0,5% associado a sedação com infusão contínua de propofol em cirurgia plástica. MÉTODO: Participaram do estudo sessenta pacientes do sexo feminino com idades entre 18 e 62 anos, estado físico ASA I ou II, submetidas a cirurgias plásticas combinadas envolvendo mama, abdômen, glúteos, lipoaspiração. Após punção peridural em T9-T10 ou T10-T11, receberam 40 ml de solução de ropivacaína a 0,5% e sufentanil 15 µg. Doses subseqüentes do anestesia local foram administradas através de cateter quando necessárias. Sedação foi obtida com infusão venosa contínua de propofol 40 a 50 µg.kg-1.min-1. Foram avaliadas as características de instalação e regressão do bloqueio, a evolução dos parâmetros hemodinâmicos e respiratórios, a incidência de eventos adversos. RESULTADOS: O nível superior de bloqueio sensorial foi T2 em 52 pacientes (86,6%, C4 em 4 (6,6% e T3 em 4 (6,6%. A média para o tempo de latência foi 9,1 ± 8,2 minutos. Obteve-se bloqueio motor grau 2 em 61,7% das pacientes e grau 1 em 38,3%. A média para o tempo de regressão completa do bloqueio motor foi 377,9 ± 68,5 minutos. A média para o tempo da primeira queixa espontânea de dor foi 965,1 ± 371,3 minutos. Os valores médios de PAS, PAD, PAM e FC decresceram significativamente em relação ao controle a partir dos 15 min após a injeção do anestésico local, caracterizando anestesia hipotensiva. Treze pacientes (21,7% que apresen- taram PAS JUSTIFICATIVA Y OBJETIVOS: El bloqueo peridural torácico constituye técnica de anestesia hipotensiva, capaz de reducir el sangramiento en el campo operatorio. El presente estudio no-comparativo tiene por finalidad observar los

  1. Kidney Fibrosis : Origins and Interventions

    NARCIS (Netherlands)

    Vanhove, Thomas; Goldschmeding, Roel|info:eu-repo/dai/nl/102376069; Kuypers, Dirk

    2017-01-01

    All causes of renal allograft injury, when severe and/or sustained, can result in chronic histological damage of which interstitial fibrosis and tubular atrophy are dominant features. Unless a specific disease process can be identified, what drives interstitial fibrosis and tubular atrophy

  2. Bloqueio combinado raquiperidural versus bloqueio peridural contínuo para analgesia de parto em primigestas: resultados maternos e perinatais Combined spinal-epidural block versus continuous epidural block in labor analgesia for primiparous women: newborns and women outcomes

    Directory of Open Access Journals (Sweden)

    Márcio Antonio de Souza

    2009-10-01

    Full Text Available OBJETIVOS: comparar a evolução materna e perinatal após a utilização da analgesia peridural contínua versus analgesia combinada raqui-peridural em parturientes primigestas. MÉTODOS: foi realizado ensaio clínico aleatorizado com 128 gestantes primigestas em trabalho de parto, divididas em dois grupos: analgesia peridural (APC com 65 mulheres e grupo analgesia combinada raqui-peridural (ACRP com 63, admitidas no pré-parto de duas maternidades na cidade de Jundiaí - SP. Foram estudadas as variáveis: tempo de latência de instalação da analgesia, intensidade da dor e tempo total decorrido até a dilatação completa, índice de Apgar no primeiro e quinto minutos, tempo de resolução do parto, grau de bloqueio motor, efeitos adversos como náuseas, vômitos, prurido, hipotensão arterial, e grau de satisfação materna. Foram critérios de inclusão: primigestas, estado físico ASA 1 e 2, feto único, apresentação cefálica, de termo, dilatação cervical de 3 a 6 cm e solicitação de analgesia pelo obstetra. Foram excluídas mulheres com morbidades, ruptura de membranas, anormalidades fetais e uso de opioides até quatro horas antes. Para a análise estatística utilizou-se o teste de Mann-Whitney para as variáveis contínuas não paramétricas e os testes exato de Fisher e χ2 de Pearson, para variáveis categóricas. RESULTADOS: não houve diferença entre os grupos para velocidade de dilatação cervical, tempo para resolução do parto, parâmetros hemodinâmicos maternos, vitalidade do recém-nascido, complementações analgésicas durante o trabalho de parto e modo de parto. Houve maior rapidez de instalação da analgesia no grupo da ACRP e menor bloqueio motor no grupo de APC. Não foram observadas diferenças em relação aos efeitos adversos como náuseas, vômitos, prurido e hipotensão, sendo hipotensão mais frequente no grupo APC (16,9 versus 6,3% e náusea no grupo ACRP (6,3 versus 3,1%. CONCLUSÕES: as duas t

  3. Serum markers of liver fibrosis

    DEFF Research Database (Denmark)

    Veidal, Sanne Skovgård; Bay-Jensen, Anne-Christine; Tougas, Gervais

    2010-01-01

    BACKGROUND: Fibrosis is a central histological feature of chronic liver diseases and is characterized by the accumulation and reorganization of the extracellular matrix. The gold standard for assessment of fibrosis is histological evaluation of a percutaneous liver biopsy. Albeit a considerable......-epitopes, may be targeted for novel biochemical marker development in fibrosis. We used the recently proposed BIPED system (Burden of disease, Investigative, Prognostic, Efficacy and Diagnostic) to characterise present serological markers. METHODS: Pubmed was search for keywords; Liver fibrosis, neo......, a systematic use of the neo-epitope approach, i.e. the quantification of peptide epitopes generated from enzymatic cleavage of proteins during extracellular remodeling, may prove productive in the quest to find new markers of liver fibrosis....

  4. Management strategies for liver fibrosis.

    Science.gov (United States)

    Altamirano-Barrera, Alejandra; Barranco-Fragoso, Beatriz; Méndez-Sánchez, Nahum

    2017-01-01

    Liver fibrosis resulting from chronic liver injury are major causes of morbidity and mortality worldwide. Among causes of hepatic fibrosis, viral infection is most common (hepatitis B and C). In addition, obesity rates worldwide have accelerated the risk of liver injury due to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Also liver fibrosis is associated with the consumption of alcohol, or autoimmune hepatitis and chronic cholangiophaties. The response of hepatocytes to inflammation plays a decisive role in the physiopathology of hepatic fibrosis, which involves the recruitment of both pro- and anti-inflammatory cells such as monocytes and macrophages. As well as the production of other cytokines and chemokines, which increase the stimulus of hepatic stellate cells by activating proinflammatory cells. The aim of this review is to identify the therapeutic options available for the treatment of the liver fibrosis, enabling the prevention of progression when is detected in time.

  5. Cannabinoids, inflammation, and fibrosis.

    Science.gov (United States)

    Zurier, Robert B; Burstein, Sumner H

    2016-11-01

    Cannabinoids apparently act on inflammation through mechanisms different from those of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs). As a class, the cannabinoids are generally free from the adverse effects associated with NSAIDs. Their clinical development thus provides a new approach to treatment of diseases characterized by acute and chronic inflammation and fibrosis. A concise survey of the anti-inflammatory actions of the phytocannabinoids Δ9-tetrahydrocannabinol (THC), cannabidiol, cannabichromene, and cannabinol is presented. Mention is also made of the noncannabinoid plant components and pyrolysis products, followed by a discussion of 3 synthetic preparations-Cesamet (nabilone; Meda Pharmaceuticals, Somerset, NJ, USA), Marinol (dronabinol; THC; AbbVie, Inc., North Chicago, IL, USA), and Sativex (Cannabis extract; GW Pharmaceuticals, Cambridge United Kingdom)-that have anti-inflammatory effects. A fourth synthetic cannabinoid, ajulemic acid (AJA; CT-3; Resunab; Corbus Pharmaceuticals, Norwood, MA, USA), is discussed in greater detail because it represents the most recent advance in this area and is currently undergoing 3 phase 2 clinical trials by Corbus Pharmaceuticals. The endogenous cannabinoids, including the closely related lipoamino acids, are then discussed. The review concludes with a presentation of a possible mechanism for the anti-inflammatory and antifibrotic actions of these substances. Thus, several cannabinoids may be considered candidates for development as anti-inflammatory and antifibrotic agents. Of special interest is their possible use for treatment of chronic inflammation, a major unmet medical need.-Zurier, R. B., Burstein, S. H. Cannabinoids, inflammation, and fibrosis. © FASEB.

  6. [Cystic fibrosis in adults].

    Science.gov (United States)

    Damas, C; Saleiro, S; Gomes, I; Marques, J Agostinho

    2007-01-01

    The authors reviewed adult cystic fibrosis patients followed in the Pulmonology Unit from 1994-2004 (n=8), five female and three male, aged 20-34 years old (median= 27 years). Patients were diagnosed at 18 months - 31 years old by sweat testing (positive in six patients) and genotyping (four patients homozygous for Delta F508 mutation). Respiratory involvement was characterised by sinusitis and bronchiectasis. Pulmonary involvement was accompanied by functional abnormalities and gas exchange impairment in the majority of the patients. Bronchial tree was colonised permanently in five patients: Pseudomonas aeruginosa in four and Staphilococcus aureus in four (three patients affected by both agents simultaneously). The main causes of exacerbation were respiratory infections and haemoptysis. Non-respiratory involvement was variable. Four patients had digestive involvement (one with hepatic cirrhosis), one had renal failure and only one had a sperm count to document infertility. Four patients had osteopaenia. Treatment included chest physiotherapy, bronchodilators, dornase alfa, mucolytics, digestive enzymes, vitamins, antibiotics and oxygen therapy. At review, one had left follow-up, one had died, one was awaiting lung transplant and the others evidenced no difference in clinical characteristics. In this group of patients the severity of the pulmonary disease was not related to a late diagnosis. It can be explained by the diversity of cystic fibrosis presentation in adults.

  7. Influência da morfina peridural na função pulmonar de pacientes submetidos à colecistectomia aberta Influencia de la morfina peridural en la función pulmonar de pacientes sometidos a la colecistectomía abierta The influence of epidural morphine in the pulmonary function of patients undergoing open cholecystectomy

    Directory of Open Access Journals (Sweden)

    Gilson Cassem Ramos

    2007-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Operações de abdome superior podem causar, no pós-operatório, disfunções ventilatórias. O objetivo do presente estudo foi avaliar a função pulmonar após colecistectomias laparoscópicas e abertas, com e sem morfina peridural. MÉTODO: Em estudo do tipo ensaio clínico duplamente encoberto e aleatório, 45 pacientes foram distribuídas em três grupos, GL, GA e GAM, de 15 componentes submetidas a colecistectomias. O grupo GL foi operado pela via laparoscópica; enquanto GA e GAM, pela via aberta, sendo que este último recebeu morfina peridural. As pacientes realizaram espirometrias e gasometrias no pré- e no pós-operatório. A hipótese de igualdade de médias entre os grupos foi verificada utilizando-se a ANOVA. Quando os resultados apresentaram diferença estatística significativa, realizava-se o teste de Tukey. A hipótese de igualdade de médias entre um mesmo grupo foi verificada por meio do teste t de Student emparelhado. O valor de p JUSTIFICATIVA Y OBJETIVOS: Operaciones de abdomen superior pueden causar en el postoperatorio, disfunciones de ventilación. El objetivo del presente estudio fue evaluar la función pulmonar después de las colecistectomías laparoscópicas y abiertas, con y sin morfina peridural. MÉTODO: En estudio del tipo ensayo clínico doblemente encubierto y aleatorio, 45 pacientes fueron distribuidas en tres grupos, GL, GA y GAM, de 15 componentes, sometidas a colecistectomías. El grupo GL fue operado por vía laparoscópica, mientras que el GA y GAM, por vía abierta, siendo que este último recibió morfina peridural. Las pacientes realizaron espirometrías y gasometrías en el pre y en el postoperatorio. La hipótesis de igualdad de promedios entre los grupos fue verificada utilizando la ANOVA. Cuando los resultados presentaron diferencia estadística significativa, se realizaba el test de Tukey. La hipótesis de igualdad de promedios entre un mismo grupo fue verificada por

  8. Short course dexamethasone treatment following injury inhibits bleomycin induced fibrosis in rats

    NARCIS (Netherlands)

    W.A. Dik (Willem); R.J. McAnulty; M.A. Versnel (Marjan); B.A. Naber (Brigitta); L.J.I. Zimmermann (Luc); G.J. Laurent; S.E. Mutsaers (Steven)

    2003-01-01

    textabstractBACKGROUND: Corticosteroids are routinely used in patients with pulmonary fibrosis. The timing for initiation of treatment is likely to be crucial for corticosteroids to exert an antifibrotic effect. Experimental studies in animals have examined the effect of

  9. Estudo comparativo entre bupivacaína a 0,25% e ropivacaína a 0,2% em anestesia peridural para cirurgia torácica Estudio comparativo entre bupivacaína a 0,25% y ropivacaína a 0,2% en anestesia peridural para cirugía de tórax Comparison between 0.25% bupivacaine and 0.2% ropivacaine in epidural anesthesia for thoracic surgery

    Directory of Open Access Journals (Sweden)

    Marcus Vinícius Martins Novaes

    2001-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A anestesia peridural associada à anestesia geral tem sido usada em várias especialidades cirúrgicas. Em cirurgia torácica seu uso é pouco discutido na literatura. Este estudo teve como objetivo avaliar os efeitos hemodinâmicos e ventilatórios da anestesia peridural torácica com bupivacaína a 0,25% e ropivacaína a 0,2% associada à anestesia geral em pacientes submetidos à toracotomia. MÉTODO: Participaram deste estudo prospectivo, comparativo e aleatório quarenta pacientes divididos em dois grupos de vinte. Cada grupo recebeu um volume de 10 ml de anestésico local, por via peridural torácica. Grupo B (Bupivacaína 0,25% e o Grupo R (Ropivacaína 0,2%. O bloqueio peridural foi realizado com os pacientes em decúbito lateral, punção paramediana e cateter para injeção dos fármacos A seguir todos os pacientes receberam anestesia geral com IOT. Foram analisados parâmetros hemodinâmicos e ventilatórios em 9 momentos. RESULTADOS: A pressão arterial sistólica foi menor no momento 5 e pressão arterial diastólica nos momentos 1 e 5, ambas no grupo B. A necessidade de efedrina para corrigir hipotensão arterial foi de 8/20 no grupo B, contra 6/20 no grupo R. A pressão de pico nas vias aéreas superiores foi sempre mais elevada no grupo R e os valores da CAM do isoflurano foram mais elevados nos momentos 5 e 6 também no Grupo R. CONCLUSÕES: A técnica combinada peridural torácica e anestesia geral mostrou-se eficaz e segura nos pacientes submetidos à toracotomia. Quando se utilizou bupivacaína, a diminuição da pressão arterial foi maior e a pressão máxima nas vias aéreas foi menor do que quando foi utilizada ropivacaína.JUSTIFICATIVA Y OBJETIVOS: La anestesia peridural asociada a anestesia general ha sido usada en varias especialidades quirúrgicas. En cirugía torácica su uso es poco discutido en la literatura. Este estudio tuvo como objetivo evaluar los efectos hemodinámicos y

  10. Gastrointestinal Manifestations of Cystic Fibrosis

    Science.gov (United States)

    2016-01-01

    Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

  11. Nephrogenic systemic fibrosis.

    LENUS (Irish Health Repository)

    Kennedy, C

    2010-11-05

    Nephroaenic systemic fibrosis (NSF) is a potentiallv fatal dermatiological condition found exclusively in patients with advanced renal I failure. There is minimal literature regarding the epidemiology and outcomes of patients with NSF in Ireland. A retrospective chart review was performed for all patients with NSF in Ireland. Ireland\\'s experience with the disease was examined in light of international reports. There have been three cases of NSF in Ireland; an area which serves 1915 dialysis patients--giving a point prevalence among Irish end-stage kidney disease patients of 0.002. There was a large variation in disease severity between the three patients. All three patients had significant exposure to gadolinium chelate. Caution with gadolinium administration must be exercised in patients with advanced renal failure.

  12. Profile of cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Mona M. El-Falaki

    2014-09-01

    Full Text Available It was generally believed that Cystic fibrosis (CF is rare among Arabs; however, the few studies available from Egypt and other Arabic countries suggested the presence of many undiagnosed patients. The aim of the present study was to determine the frequency of CF patients out of the referred cases in a single referral hospital in Egypt. A total of 100 patients clinically suspected of having CF were recruited from the CF clinic of the Allergy and Pulmonology Unit, Children’s Hospital, Cairo University, Egypt, throughout a 2 year period. Sweat chloride testing was done for all patients using the Wescor macroduct system for collection of sweat. Quantitative analysis for chloride was then done by the thiocyanate colorimetric method. Patients positive for sweat chloride (⩾60 mmol/L were tested for the ΔF508 mutation using primer specific PCR for cystic fibrosis transmembrane conductance regulator (CFTR gene. Thirty-six patients (36% had a positive sweat chloride test. The main clinical presentations in patients were chronic cough in 32 (88.9%, failure to thrive in 27 (75%, steatorrhea in 24 (66.7%, and hepatobiliary involvement in 5 (13.9%. Positive consanguinity was reported in 50% of CF patients. Thirty-two patients were screened for ΔF508 mutation. Positive ΔF508 mutation was detected in 22 (68.8% patients, 8 (25% were homozygous, 14 (43.8% were heterozygous, and 10 (31.3% tested were negative. CF was diagnosed in more than third of patients suspected of having the disease on clinical grounds. This high frequency of CF among referred patients indicates that a high index of suspicion and an increasing availability of diagnostic tests lead to the identification of a higher number of affected individuals.

  13. Quebra de cateter no espaço peridural Rotura de catéter en el espacio epidural Breakage of a catheter in the epidural space

    Directory of Open Access Journals (Sweden)

    Cristian Sbardelotto

    2008-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A quebra do cateter peridural durante sua remoção é rara, porém descrita. O conhecimento das possíveis complicações e o manuseio adequado são responsabilidades do anestesiologista. O objetivo deste relato foi apresentar caso de quebra de cateter peridural em analgesia de parto. RELATO DO CASO: Paciente do sexo feminino, 33 anos, GII, PI, deu entrada na maternidade em trabalho de parto. Após duas horas de evolução, a paciente solicitou analgesia. Ao exame, encontrava-se em fase ativa do trabalho de parto, com dilatação cervical de 5 cm, dinâmica uterina regular, bolsa rota, com dor classificada pela Escala Visual Analógica - VAS 10. Iniciada a analgesia de parto pela técnica combinada com dupla punção. Durante a evolução foi feita uma complementação analgésica pelo cateter. Na retirada houve pequena dificuldade e conseqüente rompimento do mesmo. Optou-se pela realização de uma tomografia axial computadorizada e radiografia da região lombar que não mostrou evidência do fragmento do cateter. Visto que a paciente evoluiu assintomática clinicamente, sem sinais de irritação radicular, dor ou infecção, procedeu-se às devidas orientações e alta hospitalar. CONCLUSÕES: Cateteres peridurais em região lombar são, em ocasiões raras, difíceis de remover. Fatores que podem aumentar as chances de formação de nós e risco de quebra do cateter foram relacionados. Neste caso, um dos principais fatores envolvidos foi a introdução excessiva do cateter peridural lombar. Felizmente, as complicações neurológicas são ainda mais raras, e seguindo as diretrizes de uma tração lenta e suave na ausência de parestesias, na maioria das vezes, o cateter é removido com sucesso.JUSTIFICATIVA Y OBJETIVOS: La rotura del catéter epidural durante su retirada es rara, pero ya se ha descrito. El conocimiento de las posibles complicaciones y el manejo adecuado es de total responsabilidad del anestesi

  14. Genetics Home Reference: retroperitoneal fibrosis

    Science.gov (United States)

    ... Review. Citation on PubMed Doolin EJ, Goldstein H, Kessler B, Vinocur C, Marchildon MB. Familial retroperitoneal fibrosis. ... consult with a qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Customer ...

  15. Epigenetics of Idiopathic Pulmonary Fibrosis

    OpenAIRE

    Yang, Ivana V.; Schwartz, David A.

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a complex lung disease of unknown etiology. Development of IPF is influenced by both genetic and environmental factors. Recent work by our and other groups has identified strong genetic predisposition factors for the development of pulmonary fibrosis while cigarette smoke remains the most strongly associated environmental exposure risk factor. Gene expression profiling studies of IPF lung have taught us quite a bit about the biology of this fatal disease...

  16. Targeting Interleukin-13 with Tralokinumab Attenuates Lung Fibrosis and Epithelial Damage in a Humanized SCID Idiopathic Pulmonary Fibrosis Model

    Science.gov (United States)

    Zhang, Huilan; Oak, Sameer R.; Coelho, Ana Lucia; Herath, Athula; Flaherty, Kevin R.; Lee, Joyce; Bell, Matt; Knight, Darryl A.; Martinez, Fernando J.; Sleeman, Matthew A.; Herzog, Erica L.; Hogaboam, Cory M.

    2014-01-01

    The aberrant fibrotic and repair responses in the lung are major hallmarks of idiopathic pulmonary fibrosis (IPF). Numerous antifibrotic strategies have been used in the clinic with limited success, raising the possibility that an effective therapeutic strategy in this disease must inhibit fibrosis and promote appropriate lung repair mechanisms. IL-13 represents an attractive target in IPF, but its disease association and mechanism of action remains unknown. In the present study, an overexpression of IL-13 and IL-13 pathway markers was associated with IPF, particularly a rapidly progressive form of this disease. Targeting IL-13 in a humanized experimental model of pulmonary fibrosis using tralokinumab (CAT354) was found to therapeutically block aberrant lung remodeling in this model. However, targeting IL-13 was also found to promote lung repair and to restore epithelial integrity. Thus, targeting IL-13 inhibits fibrotic processes and enhances repair processes in the lung. PMID:24325475

  17. Lactato sanguíneo na avaliação dos efeitos da peridural torácica em cães anestesiados pelo isoflurano Blood lactate in the evaluation of the thoracic epidural effects in isoflurane anesthetized dogs

    Directory of Open Access Journals (Sweden)

    Beatriz Perez Floriano

    2010-03-01

    evaluate the tissue perfusion through blood lactate in dogs submitted to thoracic peridural anesthesia. For such, eight dogs with MAC previously determined for isoflurano, were divided into two experimental groups and were induced and maintained with isofluorane. The dogs had their spinal low lumbar space reached with an epidural catheter, inserted to the T1-T2 interval, with later application of ropivacaine in two different volumes, one for each group: 0.25ml kg-1 (GR1 and 0.33ml kg-1 (GR2. The animals were monitored at nine total moments of anesthesia and electrostimulation in the radio-ulnar region was made to detect the presence of the local block, with evaluation of the following parameters: lactate levels, mean arterial pressure, hemogasometric variables, heart rate and respiratory rate. Respiratory depression was observed, caused by the block, as well as an increase on the pH and slight reduction of HR and MAP. There was a significant decrease in lactate levels after anesthetic induction and a return to its basal levels after recovery, on both groups. There was no correlation between lactate and other evaluated parameters. The changes in lactate levels are probably related to the inhalant anesthesia, assuming an influence of isofluorane on this parameter. There was no influence of the local block on tissue perfusion, analized through blood lactate measures.

  18. Expression and distribution of connexin 32 in rat liver with experimentally induced fibrosis Expressão e distribuição da conexina 32 em fígados de ratos com fibrose induzida experimentalmente

    Directory of Open Access Journals (Sweden)

    Alexandro dos S. Rodrigues

    2009-04-01

    Full Text Available The connexin 32 (Cx32 is a protein that forms the channels that promote the gap junction intercellular communication (GJIC in the liver, allowing the diffusion of small molecules through cytosol from cell-to-cell. Hepatic fibrosis is characterized by a disruption of normal tissue architeture by cellular lesions, and may alter the GJIC. This work aimed to study the expression and distribution of Cx32 in liver fibrosis induced by the oral administration of dimethylnitrosamine in female Wistar rats. The necropsy of the rats was carried out after five weeks of drug administration. They presented a hepatic fibrosis state. Sections from livers with fibrosis and from control livers were submitted to immunohistochemical, Real Time-PCR and Western-Blot analysis to Cx32. In fibrotic livers the Cxs were diffusely scattered in the cytoplasm, contrasting with the control livers, where the Cx32 formed junction plaques at the cell membrane. Also it was found a decrease in the gene expression of Cx32 without reduction in the protein quantity when compared with controls. These results suggest that there the mechanism of intercellular communication between hepatocytes was reduced by the fibrotic process, which may predispose to the occurrence of a neoplastic process, taken in account that connexins are considered tumor suppressing genes.A conexina 32 (Cx32 é uma proteína que constitui os canais que promovem as comunicações intercelulares via junções comunicantes (CIJC no fígado, permitindo difusão de pequenas moléculas citoplasmáticas de uma célula à outra. A fibrose hepática caracteriza-se pela alteração da arquitetura normal do fígado e podem alterar as CIJCs. O objetivo deste trabalho foi estudar a expressão e distribuição de Cx32 na fibrose hepática. O objetivo do presente trabalho foi estudar a expressão e distribuição da Cx32 em fígados com fibrose induzida pela administração oral de dimetilnitrosamina em fêmeas de ratos Wistar. A

  19. Idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Noble Paul W

    2008-03-01

    Full Text Available Abstract Idiopathic pulmonary fibrosis (IPF is a non-neoplastic pulmonary disease that is characterized by the formation of scar tissue within the lungs in the absence of any known provocation. IPF is a rare disease which affects approximately 5 million persons worldwide. The prevalence is estimated to be slightly greater in men (20.2/100,000 than in women (13.2/100,000. The mean age at presentation is 66 years. IPF initially manifests with symptoms of exercise-induced breathless and dry coughing. Auscultation of the lungs reveals early inspiratory crackles, predominantly located in the lower posterior lung zones upon physical exam. Clubbing is found in approximately 50% of IPF patients. Cor pulmonale develops in association with end-stage disease. In that case, classic signs of right heart failure may be present. Etiology remains incompletely understood. Some environmental factors may be associated with IPF (cigarette smoking, exposure to silica and livestock. IPF is recognized on high-resolution computed tomography by peripheral, subpleural lower lobe reticular opacities in association with subpleural honeycomb changes. IPF is associated with a pathological lesion known as usual interstitial pneumonia (UIP. The UIP pattern consists of normal lung alternating with patches of dense fibrosis, taking the form of collagen sheets. The diagnosis of IPF requires correlation of the clinical setting with radiographic images and a lung biopsy. In the absence of lung biopsy, the diagnosis of IPF can be made by defined clinical criteria that were published in guidelines endorsed by several professional societies. Differential diagnosis includes other idiopathic interstitial pneumonia, connective tissue diseases (systemic sclerosis, polymyositis, rheumatoid arthritis, forme fruste of autoimmune disorders, chronic hypersensitivity pneumonitis and other environmental (sometimes occupational exposures. IPF is typically progressive and leads to significant

  20. Enhanced Laws textures: A potential MRI surrogate marker of hepatic fibrosis in a murine model.

    Science.gov (United States)

    Li, Baojun; Jara, Hernan; Yu, Heishun; O'Brien, Michael; Soto, Jorge; Anderson, Stephan W

    2017-04-01

    To compare enhanced Laws textures derived from parametric proton density (PD) maps to other MRI surrogate markers (T 2 , PD, apparent diffusion coefficient (ADC)) in assessing degrees of liver fibrosis in an ex vivo murine model of hepatic fibrosis imaged using 11.7T MRI. This animal study was IACUC approved. Fourteen male, C57BL/6 mice were divided into control and experimental groups. The latter were fed a 3,5-dicarbethoxy-1,4-dihydrocollidine (DDC) supplemented diet to induce hepatic fibrosis. Ex vivo liver specimens were imaged using an 11.7T scanner, from which the parametric PD, T 2 , and ADC maps were generated from spin-echo pulsed field gradient and multi-echo spin-echo acquisitions. A sequential enhanced Laws texture analysis was applied to the PD maps: automated dual-clustering algorithm, optimal thresholding algorithm, global grayscale correction, and Laws texture features extraction. Degrees of fibrosis were independently assessed by digital image analysis (a.k.a. %Area Fibrosis). Scatterplot graphs comparing enhanced Laws texture features, T 2 , PD, and ADC values to degrees of fibrosis were generated and correlation coefficients were calculated. Hepatic fibrosis and the enhanced Laws texture features were strongly correlated with higher %Area Fibrosis associated with higher Laws textures (r=0.89). Without the proposed enhancements, only a moderate correlation was detected between %Area Fibrosis and unenhanced Laws texture features (r=0.70). Correlation also existed between %Area Fibrosis and ADC (r=0.86), PD (r=0.65), and T 2 (r=0.66). Higher degrees of hepatic fibrosis are associated with increased Laws textures. The proposed enhancements could improve the accuracy of Laws texture features significantly. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Pulmonary CCR2+CD4+T cells are immune regulatory and attenuate lung fibrosis development.

    Science.gov (United States)

    Milger, Katrin; Yu, Yingyan; Brudy, Eva; Irmler, Martin; Skapenko, Alla; Mayinger, Michael; Lehmann, Mareike; Beckers, Johannes; Reichenberger, Frank; Behr, Jürgen; Eickelberg, Oliver; Königshoff, Melanie; Krauss-Etschmann, Susanne

    2017-11-01

    Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade of CCL2 failed to improve the clinical course of patients with lung fibrosis. However, as levels of CCR2 + CD4 + T cells in paediatric lung fibrosis had previously been found to be increased, correlating with clinical symptoms, we hypothesised that distinct CCR2 + cell populations might either increase or decrease disease pathogenesis depending on their subtype. To investigate the role of CCR2 + CD4 + T cells in experimental lung fibrosis and in patients with idiopathic pulmonary fibrosis and other fibrosis. Pulmonary CCR2 + CD4 + T cells were analysed using flow cytometry and mRNA profiling, followed by in silico pathway analysis, in vitro assays and adoptive transfer experiments. Frequencies of CCR2 + CD4 + T cells were increased in experimental fibrosis-specifically the CD62L - CD44 + effector memory T cell phenotype, displaying a distinct chemokine receptor profile. mRNA profiling of isolated CCR2 + CD4 + T cells from fibrotic lungs suggested immune regulatory functions, a finding that was confirmed in vitro using suppressor assays. Importantly, adoptive transfer of CCR2 + CD4 + T cells attenuated fibrosis development. The results were partly corroborated in patients with lung fibrosis, by showing higher percentages of Foxp3 + CD25 + cells within bronchoalveolar lavage fluid CCR2 + CD4 + T cells as compared with CCR2 - CD4 + T cells. Pulmonary CCR2 + CD4 + T cells are immunosuppressive, and could attenuate lung inflammation and fibrosis. Therapeutic strategies completely abrogating CCR2-dependent signalling will therefore also eliminate cell populations with protective roles in fibrotic lung disease. This emphasises the need for a detailed understanding of the functions of immune cell subsets in fibrotic lung disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights

  2. Efeitos do bloqueio pudendo, peridural e subaracnóideo sobre a coagulação sangüínea de gestantes Efectos del bloqueo pudendo, peridural y subaracnoideo sobre la coagulación sanguínea de embarazadas Effects of pudendal nerve, epidural and subarachnoid block on coagulation of pregnant women

    Directory of Open Access Journals (Sweden)

    Alberto Vasconcelos

    2008-04-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Tem sido atribuída à anestesia regional diminuição significativa das complicações tromboembólicas no pós-operatório, provavelmente por sua ação atenuadora sobre a resposta neuroendócrino-metabólica. As gestantes, que apresentam aumento importante da coagulabilidade sangüínea, podem, teoricamente, beneficiar-se desse efeito por ocasião do parto. O objetivo deste estudo foi verificar o efeito da anestesia regional sobre a coagulação sangüínea em gestantes. MÉTODO: Foram estudadas 30 pacientes no terceiro trimestre de gestação, sendo dez submetidas à anestesia peridural para cesariana, com 150 mg de bupivacaína a 0,5% sem epinefrina e 2 mg de morfina (grupo PD; dez à anestesia subaracnóidea para cesariana com 15 mg de bupivacaína hiperbárica a 0,5% e 0,2 mg de morfina (grupo SA; e dez a bloqueio de pudendo para parto vaginal, com doses de até 100 mg de bupivacaína a 0,5% sem epinefrina (grupo BP. A coagulação sangüínea foi avaliada por meio de coagulograma (tempo de protrombina, tempo de trombina, tempo de tromboplastina parcial ativada e de tromboelastograma (tempo r, tempo k, tempo r + k, ângulo alfa e amplitude máxima nos seguintes momentos: antes e após a anestesia, após o nascimento do feto e 24 horas após a anestesia nos grupos PD e SA. No grupo BP a avaliação foi realizada antes da anestesia, após o nascimento do feto e 24 horas após a anestesia. RESULTADOS: Os resultados mostraram que nenhuma das técnicas anestésicas utilizadas teve influência na coagulação sangüínea das gestantes. Demonstraram, também, que durante o trabalho de parto tem início um processo de ativação da coagulação que é responsável pelas alterações encontradas nos três grupos estudados. CONCLUSÕES: Nas condições do presente estudo o bloqueio simpático e o anestésico local não influíram sobre a coagulação em gestantes de termo submetidas à anestesia peridural, subaracn

  3. Myocardial Fibrosis in Congenital Heart Disease.

    Science.gov (United States)

    Rathod, Rahul H; Powell, Andrew J; Geva, Tal

    2016-05-25

    Myocardial fibrosis is common in patients with congenital heart disease (CHD) and has been associated with arrhythmias, decreased functional status, and adverse ventricular mechanics. There are multiple types of myocardial fibrosis that occur in response to different pathophysiologic stimuli. Recent advances in imaging technology have made detection and quantification of the types of myocardial fibrosis possible. In this review, we describe the pathophysiology of myocardial fibrosis, examine the imaging techniques used to evaluate fibrosis, and discuss the relationship between myocardial fibrosis and clinical outcomes in CHD. (Circ J 2016; 80: 1300-1307).

  4. Injeção peridural de lidocaína associada à xilazina ou detomidina na prevenção da dor pós-incisional em éguas

    OpenAIRE

    Silva, Gabriel Bottini da [UNESP

    2009-01-01

    A medula espinhal tem importante papel no mecanismo de transmissão dos impulsos nervosos nociceptivos. O bloqueio desses impulsos interrompe ou minimiza a dor derivada da liberação de mediadores inflamatórios deletérios ao organismo. Assim ela tem sido sede de administração de fármacos, tanto para a realização de bloqueios anestésicos, quanto para a prevenção da dor pós-operatória. Em éguas é comum a indicação do uso da via peridural caudal para a administração de fármacos como nos casos de p...

  5. Tampão peridural com dextran 40 na profilaxia da cefaléia pós-punção acidental da duramáter em paciente HIV positivo: relato de caso

    OpenAIRE

    Cruvinel, Marcos Guilherme Cunha; Barbosa, Paulo Roberto Vieira; Teixeira, Vera Coelho; Castro, Carlos Henrique Viana de

    2002-01-01

    JUSTIFICATIVA E OBJETIVOS: A cefaléia pós-punção de duramáter é uma complicação bem conhecida das anestesias subaracnóideas e peridurais, sendo o tampão sangüíneo considerado o tratamento mais eficaz, até o momento. Este é um procedimento invasivo e sujeito a complicações graves. Seu uso em certos pacientes, como portadores de HIV ou leucemias, é motivo de debate. Várias alternativas têm sido relatadas. O objetivo deste artigo é apresentar um caso do uso do tampão peridural com dextran 40 na ...

  6. What Are the Signs and Symptoms of Cystic Fibrosis?

    Science.gov (United States)

    ... Research Home / Cystic Fibrosis Cystic Fibrosis What Is Cystic fibrosis (SIS-tik fi-BRO- ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  7. Breakdown in Breathing: The Complexities of Cystic Fibrosis

    Science.gov (United States)

    ... Healthier Lungs in Kids Wise Choices Living with Cystic Fibrosis In between checkups, practice good self-care and ... joining a patient support group. Links What Is Cystic Fibrosis? Learning About Cystic Fibrosis NIH Cystic Fibrosis Fact ...

  8. Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model

    Directory of Open Access Journals (Sweden)

    Arianne van Koppen

    2018-01-01

    Conclusions: An early predictive molecular signature was identified that marked the active profibrotic process before histopathologic fibrosis becomes manifest. Early detection of the onset of NASH and fibrosis enables identification of novel blood-based biomarkers to stratify patients at risk, development of new therapeutics, and help shorten (preclinical experimental time frames.

  9. Efeito analgésico intra-operatório da cetamina, clonidina ou dexmedetomidina, administradas por via peridural, em cirurgia de abdômen superior Efecto analgésico intra-operatorio de la cetamina, clonidina o dexmedetomidina, administradas por vía peridural, en cirugía de abdomen superior Intraoperative analgesic effect of epidural ketamine, clonidine or dexmedetomidine for upper abdominal surgery

    Directory of Open Access Journals (Sweden)

    Taylor Brandão Schnaider

    2005-10-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A cetamina reduz a nocicepção, bloqueando os canais dos receptores NMDA, em doses sub-anestésicas. A ativação dos receptores alfa2-adrenérgicos induz intensa resposta analgésica. O objetivo desta pesquisa foi avaliar os efeitos da cetamina, clonidina e dexmedetomidina, por via peridural, em pacientes submetidos à cirurgia do abdômen superior. MÉTODO: Participaram deste estudo aleatório e duplamente encoberto, 70 pacientes, de ambos os gêneros, com idade entre 18 e 50 anos, estado físico ASA I e II, submetidos a colecistectomia por via subcostal, sob anestesia geral associada à peridural lombar. Na anestesia peridural foram administrados, aleatoriamente, 20 mL de ropivacaína a 0,75% e 1 mL de cloreto de sódio a 0,9% no grupo Controle (n = 10; 20 mL de ropivacaína a 0,75% e 0,5 mg.kg-1 de cetamina no grupo Cetamina (n = 20; 20 mL de ropivacaína a 0,75% e 1 mL de clonidina (150 µg no grupo Clonidina (n = 20 ou 20 mL de ropivacaína a 0,75% e 2 µg.kg-1 de dexmedetomidina no grupo Dexmedetomidina (n = 20. A indução anestésica foi realizada com etomidato, alfentanil e rocurônio, sendo a manutenção obtida pela administração de isoflurano e alfentanil. A analgesia foi observada por meio dos sinais clínicos e a concentração inspirada do agente inalatório por meio do analisador de gases ins e expirados, durante o ato operatório. RESULTADOS: Nos pacientes em que foi administrada cetamina, clonidina ou dexmedetomidina, ocorreu diminuição da freqüência cardíaca e da pressão arterial sistêmica, e não houve necessidade de complementação analgésica peri-operatória. Com relação à concentração inspirada do isoflurano, as necessidades variaram entre 0,5vol% e 1vol%, não se observando sinais clínicos ou respostas que sugerissem níveis inadequados de anestesia. CONCLUSÕES: A administração de cetamina, clonidina ou dexmedetomidina, por via peridural, reduz o consumo de alfentanil e a

  10. Nephrogenic systemic fibrosis

    Directory of Open Access Journals (Sweden)

    Bhushan Madke

    2011-01-01

    Full Text Available Nephrogenic systemic fibrosis (NSF is a relatively new fibrosing disorder which has caught the attention of various specialities in the past decade. NSF is an extremely disabling and often painful condition, affecting up to 13% of the individuals with chronic kidney disease. The administration of a gadolinium chelate contrast agent has been reported to induce the development of NSF, particularly in patients who have acute or chronic renal disease with a glomerular filtration rate (GFR lower than 30-mL/min/1.73 m 2 and in those with acute renal insufficiency. Mass spectroscopy studies have demonstrated particles of gadolinium in the lesional tissue. The exact pathogenesis of this curious sclerosing condition is unknown. The role of the aberrant targeting of ′circulating fibrocytes′ to the peripheral tissues and viscera has been hypothesized. NSF has distinct clinicopathological features in the setting of renal failure and needs to be looked upon as a new entity on the block. The condition is characterized by irregular indurated plaques, with amoeba-like projections and islands of sparing, chiefly on the trunk and extremities. Flexion contractures of fingers, knees, and elbow joints are known to occur in advanced cases of NSF. The course is frequently associated with painful episodes and loss of ambulation. Histopathology shows haphazard arrangement of thickened bundles of collagen, varying amount of mucin, and increased population of fibroblast-like cells in the dermis. Immunohistochemistry shows increased deposition of type-I procollagen and CD 34+ cells having fibroblastic activity. The condition is refractory to treatment with corticosteroids and immunosuppressive agents. Various modalities of therapy such as UVA1 phototherapy, imatinib mesylate, photodynamic therapy, plasmapheresis, extracorporeal photochemotherapy, and high-dose intravenous immunoglobulin have shown a moderate degree of improvement in skin thickness scores. A prudent

  11. Cystic fibrosis in adults

    Directory of Open Access Journals (Sweden)

    C. Damas

    2007-05-01

    Full Text Available The authors reviewed adult cystic fibrosis patients followed in the Pulmonology Unit from 1994-2004 (n = 8, five female and three male, aged 20-34 years old (median = 27 years. Patients were diagnosed at 18 months - 31 years old by sweat testing (positive in six patients and genotyping (four patients homozygous for ΔF508 mutation.Respiratory involvement was characterised by sinusitis and bronchiectasis. Pulmonary involvement was accompanied by functional abnormalities and gas exchange impairment in the majority of the patients. Bronchial tree was colonised permanently in five patients: Pseudomonas aeruginosa in four and Staphilococcus aureus in four (three patients affected by both agents simultaneously.The main causes of exacerbation were respiratory infections and haemoptysis.Non-respiratory involvement was variable. Four patients had digestive involvement (one with hepatic cirrhosis, one had renal failure and only one had a sperm count to document infertility. Four patients had osteopaenia.Treatment included chest physiotherapy, bronchodilators, dornase alfa, mucolytics, digestive enzymes, vitamins, antibiotics and oxygen therapy.At review, one had left follow-up, one had died, one was awaiting lung transplant and the others evidenced no difference in clinical characteristics.In this group of patients the severity of the pulmonary disease was not related to a late diagnosis. It can be explained by the diversity of cystic fibrosis presentation in adults Resumo: Os autores efectuaram uma revisão de doentes adultos com fibrose quística (FQ, seguidos na consulta de Pneumologia no período de 1994-2004 (n = 8: cinco mulheres e três homens, com idades compreendidas entre 20 e 34 anos (mediana  =  27 anos, cuja idade de diagnóstico variou entre os 18 meses e os 31 anos.O diagnóstico foi obtido por prova de suor (positiva em seis doentes e estudo genético (homozigotia para a mutação ΔF508 em

  12. Pathological assessment of liver fibrosis regression

    Directory of Open Access Journals (Sweden)

    WANG Bingqiong

    2017-03-01

    Full Text Available Hepatic fibrosis is the common pathological outcome of chronic hepatic diseases. An accurate assessment of fibrosis degree provides an important reference for a definite diagnosis of diseases, treatment decision-making, treatment outcome monitoring, and prognostic evaluation. At present, many clinical studies have proven that regression of hepatic fibrosis and early-stage liver cirrhosis can be achieved by effective treatment, and a correct evaluation of fibrosis regression has become a hot topic in clinical research. Liver biopsy has long been regarded as the gold standard for the assessment of hepatic fibrosis, and thus it plays an important role in the evaluation of fibrosis regression. This article reviews the clinical application of current pathological staging systems in the evaluation of fibrosis regression from the perspectives of semi-quantitative scoring system, quantitative approach, and qualitative approach, in order to propose a better pathological evaluation system for the assessment of fibrosis regression.

  13. Biomarkers in patients with myocardial fibrosis

    Directory of Open Access Journals (Sweden)

    An Zhe

    2017-10-01

    Full Text Available Myocardial fibrosis is observed in many cardiovascular diseases including hypertension, heart failure and cardiomyopathy. Myocardial fibrosis has been proved to be reversible and treatable only under timely intervention, which makes early detection and assessment of fibrosis crucial. Aside from tissue biopsy as the gold standard for the diagnosis of myocardial fibrosis, circulating biomarkers have been adopted as noninvasive assessment of this lesion. Dysregulated collagen deposition is thought to be the major cause of myocardial fibrosis. Collagens, procollagens, TGF-β, TIMP, galectin-3, and microRNAs are thought to be indicators of myocardial fibrosis. In this review, we summarize the molecules that are frequently used as biomarkers in diagnosis of cardiac fibrosis. Mechanisms of fibrosis that they take part in are also introduced.

  14. Fibrosis imaging : Current concepts and future directions

    NARCIS (Netherlands)

    Baues, Maike; Dasgupta, Anshuman; Ehling, Josef; Prakash, Jai; Boor, Peter; Tacke, Frank; Kiessling, Fabian; Lammers, Twan

    2017-01-01

    Fibrosis plays an important role in many different pathologies. It results from tissue injury, chronic inflammation, autoimmune reactions and genetic alterations, and it is characterized by the excessive deposition of extracellular matrix components. Biopsies are routinely employed for fibrosis

  15. Targeting ion channels in cystic fibrosis

    National Research Council Canada - National Science Library

    Mall, Marcus A; Galietta, Luis J V

    2015-01-01

    Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause a characteristic defect in epithelial ion transport that plays a central role in the pathogenesis of cystic fibrosis (CF...

  16. Cystic Fibrosis (CF) Respiratory Screen: Sputum

    Science.gov (United States)

    ... of Braces Eating Disorders Mitral Valve Prolapse Arrhythmias Cystic Fibrosis (CF) Respiratory Screen: Sputum KidsHealth > For Parents > Cystic Fibrosis (CF) Respiratory Screen: Sputum Print A A A ...

  17. Cystic Fibrosis: Prenatal Screening and Diagnosis

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG Cystic Fibrosis: Prenatal Screening and Diagnosis Home For Patients Search ... Screening and Diagnosis FAQ171, June 2017 PDF Format Cystic Fibrosis: Prenatal Screening and Diagnosis Pregnancy What is cystic ...

  18. Liver fibrosis in alcoholic liver disease.

    Science.gov (United States)

    Bataller, Ramon; Gao, Bin

    2015-05-01

    Excessive alcohol consumption causes a wide spectrum of liver disease, ranging from simple steatosis to severe forms of liver injury such as steatohepatitis, liver fibrosis, cirrhosis, and liver cancer. Moreover, alcohol consumption also accelerates liver fibrosis in patients with other types of liver diseases such as viral hepatitis and nonalcoholic fatty liver disease. Virtually all clinical complications of alcoholic liver disease occur in patients with established fibrosis and cirrhosis, thus making fibrosis a key parameter for treatment and prognosis of patients. Here, the authors review diagnosis, management, and antifibrotic therapy of alcoholic liver fibrosis. They discuss both the unique features of alcoholic liver fibrosis and the similarities to liver fibrosis from other etiologies, and review molecular pathogenesis and animal models. Finally, future directions for basic and clinical research on alcoholic liver fibrosis are proposed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  19. Pulmonary Fibrosis in BALB/c Mice Caused by Long-Term Instillation of Bleomycin

    OpenAIRE

    NAKAJIMA, Masamitsu

    1992-01-01

    It is well-known that bleomycin-induced pulmonary fibrosis is difficult to produce in BALB/c mice. To see whether bleomycin could induce pulmonary fibrosis in BALB/c mice, we repeatedly administered this drug through the airway for 10 consecutive days. Our experiment clearly showed that fibrosis can be induced, although it was rather mild, and also suggested that the bronchiolar and alveolar epithelia are the primary sites of injury. We believe this experimental model may be useful in studyin...

  20. What's it Like to Have Cystic Fibrosis?

    Science.gov (United States)

    ... Right Weight for Me? Your Teeth Heart Murmurs Cystic Fibrosis KidsHealth > For Kids > Cystic Fibrosis Print A A A What's in this article? ... with a condition she's known all her life — cystic fibrosis (say: SIS-tik fi-BRO-sus). Her parents ...

  1. Nephrogenic systemic fibrosis: epidemiology update

    DEFF Research Database (Denmark)

    Marckmann, P.

    2008-01-01

    Purpose of review The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. Recent findings Epidemiological and histochemical studies demonstrated that gadoli......Purpose of review The aim of this article is to outline the history of nephrogenic systemic fibrosis, a new and serious disease of patients with renal failure, and to give an update on its aetiology and prevalence. Recent findings Epidemiological and histochemical studies demonstrated...

  2. Age-Dependent Susceptibility to Pulmonary Fibrosis Is Associated with NLRP3 Inflammasome Activation

    OpenAIRE

    Stout-Delgado, Heather W.; Cho, Soo Jung; Chu, Sarah G.; Mitzel, Dana N.; Villalba, Julian; El-Chemaly, Souheil; Ryter, Stefan W.; Choi, Augustine M. K.; Rosas, Ivan O.

    2016-01-01

    Aging has been implicated in the development of pulmonary fibrosis, which has seen a sharp increase in incidence in those older than 50 years. Recent studies demonstrate a role for the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome and its regulated cytokines in experimental lung fibrosis. In this study, we tested the hypothesis that age-related NLRP3 inflammasome activation is an important predisposing factor in the develop...

  3. From granuloma to fibrosis: sarcoidosis associated pulmonary fibrosis.

    Science.gov (United States)

    Bonham, Catherine A; Strek, Mary E; Patterson, Karen C

    2016-09-01

    Up to twenty percent of patients with sarcoidosis develop pulmonary fibrosis, transforming an often benign disease into a highly morbid and potentially fatal one. We highlight the fibrotic pulmonary sarcoidosis phenotype as an area of intense clinical and translational investigation, review recent developments in treatment, and provide a roadmap for future research in sarcoidosis associated pulmonary fibrosis. Granulomatous inflammation in a lymphatic distribution is the hallmark finding of pulmonary sarcoidosis and the nidus for fibrosis. Recent research demonstrates that fibrotic sarcoidosis begins in the setting of persistent, uncontrolled inflammation, and is aided by pro-fibrotic genetic features and immune responses. Comparison to other fibrotic lung diseases also reveals key features that inform our understanding of common pathways in fibrosis. Understanding the mechanisms of fibrotic transformation in sarcoidosis enhances clinical care and facilitates development of novel therapeutic options. The impact of these findings in fibrotic sarcoidosis may be amplified through application to other interstitial lung diseases marked by inflammatory to fibrotic transformation. Important aspects of clinical management of fibrotic sarcoidosis include surveillance for co-morbidities, such as pulmonary hypertension, airway disease, and infection, and assessment for pulmonary disease activity that may benefit from immunosuppression.

  4. Efeitos adversos do sufentanil associado ao anestésico local pelas vias subaracnóidea e peridural em pacientes submetidas à analgesia de parto Efectos adversos del sufentanil asociado al anestésico local por las vías subaracnoidea y peridural en pacientes sometidas a la analgesia de parto Side effects of subarachnoid and epidural sufentanil associated with a local anesthetic in patients undergoing labor analgesia

    Directory of Open Access Journals (Sweden)

    Isabel C.F. Salem

    2007-04-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A associação do opióide ao anestésico local melhora a qualidade da analgesia de parto e reduz o risco de toxicidade sistêmica pelo anestésico local. Os opióides, entretanto, podem determinar efeitos colaterais. O objetivo desta pesquisa foi comparar os efeitos adversos determinados pelo sufentanil, administrado por via subaracnóidea, associado à bupivacaína, com aquele determinado pelo sufentanil por via peridural, associado à ropivacaína, nas doses utilizadas no Serviço de Anestesia, em gestantes submetidas à analgesia de parto. MÉTODO: Participaram do estudo 60 pacientes, estado físico ASA I e II, com idade entre 15 e 42 anos, com gestação a termo e fetos saudáveis, submetidas à analgesia de parto. Foram distribuídas de forma aleatória em dois grupos: G1 - Duplo bloqueio - bupivacaína a 0,5% (2,5 mg e sufentanil (5 µg pela via subaracnóidea, G2 - Peridural - ropivacaína a 0,2% (20 mg e sufentanil (10 µg pela via peridural. Para doses complementares foi administrada ropivacaína a 0,2% (12 mg e para resolução do parto, ropivacaína a 1% (50 mg. As pacientes foram avaliadas após analgesia (M1 com relação a hipotensão arterial, bradicardia materna, prurido, náusea, vômito, depressão respiratória e sedação. No pós-operatório (M2, quanto à presença de náusea, vômito, prurido, sedação, retenção urinária e dor. Os recém-nascidos foram avaliados pelo índice de Apgar. Para análise estatística, foram utilizados teste t de Student, Mann-Whitney e Qui-quadrado. RESULTADOS: Os grupos foram similares com relação à idade, ao peso, à altura, à duração do período de trabalho de parto após analgesia, ao Apgar dos recém-nascidos, à ocorrência de hipotensão arterial, bradicardia, náusea, vômito, prurido e retenção urinária. A sedação foi mais freqüente nas pacientes de G2, em M1 (50% com diferença estatística significativa. CONCLUSÕES: O sufentanil nas doses

  5. Analgesia e sedação da associação da clonidina e ropivacaína a 0,75% por via peridural no pós-operatório de colecistectomia aberta Analgesia y sedación de la asociación de la clonidina y ropivacaína a 0,75% por vía peridural en el pos-operatorio de colecistectomia abierta Analgesia and sedation with epidural clonidine associated to 0.75% ropivacaine in the postoperative period of open cholecystectomy

    Directory of Open Access Journals (Sweden)

    Antonio Mauro Vieira

    2003-09-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A clonidina, quando administrada por via peridural, possui propriedades analgésicas e potencializa os efeitos dos anestésicos locais, ocorrendo, contudo, efeitos colaterais que incluem hipotensão arterial, bradicardia e sedação. O objetivo desse trabalho foi avaliar a analgesia e a sedação da clonidina associada à ropivacaína a 0,75% no pós-operatório de colecistectomia aberta. MÉTODO: Participaram da pesquisa 30 pacientes, de ambos os sexos, com idades variando de 18 a 50 anos, peso entre 50 e 100 kg, estado físico ASA I e II, submetidos à colecistectomia, os quais foram distribuídos em dois grupos: Controle (GC, em que foi administrada ropivacaína a 0,75% (20 ml, associada ao cloreto de sódio a 0,9% (1 ml; Experimento (GE, em que foi injetada ropivacaína a 0,75% (20 ml, associada à clonidina (1 ml = 150 µg. A analgesia e a sedação foram observadas 2, 6 e 24 horas após o término do ato operatório. RESULTADOS: A média de idade no GC foi de 41 anos e de 37 anos no GE. A média de peso foi de 67 kg no GC e de 64 kg no GE. A sedação no pós-operatório foi significativamente maior nos pacientes as 2 e 6 horas do grupo experimento. A analgesia foi observada em maior número de pacientes do grupo experimento, quando comparada ao grupo controle. CONCLUSÕES: A associação de clonidina e ropivacaína produziu analgesia mais duradoura e sedação em pacientes, nos horários de observação de 2 e 6 horas.JUSTIFICATIVA Y OBJETIVOS: La clonidina, cuando administrada por vía peridural, posee propiedades analgésicas y potencializa los efectos de los anestésicos locales, ocurriendo por ello, efectos colaterales que incluyen hipotensión, bradicardia y sedación. El objetivo de ese trabajo fue evaluar la analgesia y la sedación de la clonidina asociada a la ropivacaína a 0,75% en el pos-operatorio de colecistectomia abierta. MÉTODO: Participaron de la pesquisa 30 pacientes, de ambos sexos, con

  6. Update on nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Marckmann, P.; Logager, V.B.; Thomsen, Henrik S.

    2008-01-01

    Gadolinium-based contrast agents were for many years considered safe, but this is no longer the case. The least stable agents may trigger the development of nephrogenic systemic fibrosis (NSF), a generalized fibrotic disorder, in renal failure patients. The use of gadodiamide and gadopentetate di...

  7. Meconium ileus in Cystic Fibrosis

    NARCIS (Netherlands)

    Sathe, Meghana; Houwen, Roderick|info:eu-repo/dai/nl/087887991

    2017-01-01

    Meconium ileus (MI) is often the first manifestation of cystic fibrosis (CF) and occurs in approximately 20% of patients diagnosed with CF. This article reviews the pathophysiology of MI and its clinical presentation. It focuses on the medical and surgical management emphasizing the importance of

  8. Cough in idiopathic pulmonary fibrosis

    NARCIS (Netherlands)

    M.J.G. Van Manen (Mirjam J.G.); S.S. Birring (Surinder S.); C. Vancheri (Carlo); V. Cottin (Vincent); Renzoni, E.A. (Elisabetta A.); Russell, A.-M. (Anne-Marie); M.S. Wijsenbeek (Marlies)

    2016-01-01

    textabstractMany patients with idiopathic pulmonary fibrosis (IPF) complain of chronic refractory cough. Chronic cough is a distressing and disabling symptom with a major impact on quality of life. During recent years, progress has been made in gaining insight into the pathogenesis of cough in IPF,

  9. Autophagy in idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Avignat S Patel

    Full Text Available Autophagy is a basic cellular homeostatic process important to cell fate decisions under conditions of stress. Dysregulation of autophagy impacts numerous human diseases including cancer and chronic obstructive lung disease. This study investigates the role of autophagy in idiopathic pulmonary fibrosis.Human lung tissues from patients with IPF were analyzed for autophagy markers and modulating proteins using western blotting, confocal microscopy and transmission electron microscopy. To study the effects of TGF-β(1 on autophagy, human lung fibroblasts were monitored by fluorescence microscopy and western blotting. In vivo experiments were done using the bleomycin-induced fibrosis mouse model.Lung tissues from IPF patients demonstrate evidence of decreased autophagic activity as assessed by LC3, p62 protein expression and immunofluorescence, and numbers of autophagosomes. TGF-β(1 inhibits autophagy in fibroblasts in vitro at least in part via activation of mTORC1; expression of TIGAR is also increased in response to TGF-β(1. In the bleomycin model of pulmonary fibrosis, rapamycin treatment is antifibrotic, and rapamycin also decreases expression of á-smooth muscle actin and fibronectin by fibroblasts in vitro. Inhibition of key regulators of autophagy, LC3 and beclin-1, leads to the opposite effect on fibroblast expression of á-smooth muscle actin and fibronectin.Autophagy is not induced in pulmonary fibrosis despite activation of pathways known to promote autophagy. Impairment of autophagy by TGF-β(1 may represent a mechanism for the promotion of fibrogenesis in IPF.

  10. Endomyocardial Fibrosis Associated With Schistosoma ...

    African Journals Online (AJOL)

    2014-12-01

    Dec 1, 2014 ... SUMMARY. Endomyocardial fibrosis (EMF) is a form of restrictive cardiomyopathy common in the tropics and subtropics. The aetiology of EMF is unknown but helminth infes- tations such as schistosomiasis have been implicated. Two boys aged 8 and 10 years with EMF associated with Schistosoma ...

  11. Imaging biomarkers in liver fibrosis.

    Science.gov (United States)

    Berzigotti, A; França, M; Martí-Aguado, D; Martí-Bonmatí, L

    2017-11-03

    There is a need for early identification of patients with chronic liver diseases due to their increasing prevalence and morbidity-mortality. The degree of liver fibrosis determines the prognosis and therapeutic options in this population. Liver biopsy represents the reference standard for fibrosis staging. However, given its limitations and complications, different non-invasive methods have been developed recently for the in vivo quantification of fibrosis. Due to their precision and reliability, biomarkers' measurements derived from Ultrasound and Magnetic Resonance stand out. This article reviews the different acquisition techniques and image processing methods currently used in the evaluation of liver fibrosis, focusing on their diagnostic performance, applicability and clinical value. In order to properly interpret their results in the appropriate clinical context, it seems necessary to understand the techniques and their quality parameters, the standardization and validation of the measurement units and the quality control of the methodological problems. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis

    Directory of Open Access Journals (Sweden)

    Amit Sharma

    2016-05-01

    Full Text Available Cytochrome P450 (CYP monooxygenases epoxidize the omega-3 polyunsaturated fatty acid (PUFA docosahexaenoic acid into novel epoxydocosapentaenoic acids (EDPs that have multiple biological actions. The present study determined the ability of the most abundant EDP regioisomer, 19,20-EDP to reduce kidney injury in an experimental unilateral ureteral obstruction (UUO renal fibrosis mouse model. Mice with UUO developed kidney tubular injury and interstitial fibrosis. UUO mice had elevated kidney hydroxyproline content and five-times greater collagen positive fibrotic area than sham control mice. 19,20-EDP treatment to UUO mice for 10 days reduced renal fibrosis with a 40%–50% reduction in collagen positive area and hydroxyproline content. There was a six-fold increase in kidney α-smooth muscle actin (α-SMA positive area in UUO mice compared to sham control mice, and 19,20-EDP treatment to UUO mice decreased α-SMA immunopositive area by 60%. UUO mice demonstrated renal epithelial-to-mesenchymal transition (EMT with reduced expression of the epithelial marker E-cadherin and elevated expression of multiple mesenchymal markers (FSP-1, α-SMA, and desmin. Interestingly, 19,20-EDP treatment reduced renal EMT in UUO by decreasing mesenchymal and increasing epithelial marker expression. Overall, we demonstrate that a novel omega-3 fatty acid metabolite 19,20-EDP, prevents UUO-induced renal fibrosis in mice by reducing renal EMT.

  13. Panax notoginseng Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice

    Directory of Open Access Journals (Sweden)

    Kuen-Daw Tsai

    2011-01-01

    Full Text Available Panax notoginseng (PN is a traditional Chinese herb experimentally proven to have anti-inflammatory effects, and it is used clinically for the treatment of atherosclerosis, cerebral infarction, and cerebral ischemia. This study aimed to determine the anti-inflammatory effects of PN against bleomycin-induced pulmonary fibrosis in mice. First, in an in vitro study, culture media containing lipopolysaccharide (LPS was used to stimulate macrophage cells (RAW 264.7 cell line. TNF-α and IL-6 levels were then determined before and after treatment with PN extract. In an animal model (C57BL/6 mice, a single dose of PN (0.5 mg/kg was administered orally on Day 2 or Day 7 postbleomycin treatment. The results showed that TNF-α and IL-6 levels increased in the culture media of LPS-stimulated macrophage cells, and this effect was significantly inhibited in a concentration-dependent manner by PN extract. Histopathologic examination revealed that PN administered on Day 7 postbleomycin treatment significantly decreased inflammatory cell infiltrates, fibrosis scores, and TNF-α, TGF-β, IL-1β, and IL-6 levels in bronchoalveolar lavage fluid when compared with PN given on Day 2 postbleomycin treatment. These results suggest that PN administered in the early fibrotic stage can attenuate pulmonary fibrosis in an animal model of idiopathic pulmonary fibrosis.

  14. Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis

    Science.gov (United States)

    Kisseleva, Tatiana; Cong, Min; Paik, YongHan; Scholten, David; Jiang, Chunyan; Benner, Chris; Iwaisako, Keiko; Moore-Morris, Thomas; Scott, Brian; Tsukamoto, Hidekazu; Evans, Sylvia M.; Dillmann, Wolfgang; Glass, Christopher K.; Brenner, David A.

    2012-01-01

    Myofibroblasts produce the fibrous scar in hepatic fibrosis. In the carbon tetrachloride (CCl4) model of liver fibrosis, quiescent hepatic stellate cells (HSC) are activated to become myofibroblasts. When the underlying etiological agent is removed, clinical and experimental fibrosis undergoes a remarkable regression with complete disappearance of these myofibroblasts. Although some myofibroblasts apoptose, it is unknown whether other myofibroblasts may revert to an inactive phenotype during regression of fibrosis. We elucidated the fate of HSCs/myofibroblasts during recovery from CCl4- and alcohol-induced liver fibrosis using Cre-LoxP–based genetic labeling of myofibroblasts. Here we demonstrate that half of the myofibroblasts escape apoptosis during regression of liver fibrosis, down-regulate fibrogenic genes, and acquire a phenotype similar to, but distinct from, quiescent HSCs in their ability to more rapidly reactivate into myofibroblasts in response to fibrogenic stimuli and strongly contribute to liver fibrosis. Inactivation of HSCs was associated with up-regulation of the anti-apoptotic genes Hspa1a/b, which participate in the survival of HSCs in culture and in vivo. PMID:22566629

  15. Hypoxia-induced deoxycytidine kinase contributes to epithelial proliferation in pulmonary fibrosis.

    Science.gov (United States)

    Weng, Tingting; Poth, Jens M; Karmouty-Quintana, Harry; Garcia-Morales, Luis J; Melicoff, Ernestina; Luo, Fayong; Chen, Ning-yuan; Evans, Christopher M; Bunge, Raquel R; Bruckner, Brian A; Loebe, Matthias; Volcik, Kelly A; Eltzschig, Holger K; Blackburn, Michael R

    2014-12-15

    Idiopathic pulmonary fibrosis (IPF) is a deadly lung disease with few therapeutic options. Apoptosis of alveolar epithelial cells, followed by abnormal tissue repair characterized by hyperplastic epithelial cell formation, is a pathogenic process that contributes to the progression of pulmonary fibrosis. However, the signaling pathways responsible for increased proliferation of epithelial cells remain poorly understood. To investigate the role of deoxycytidine kinase (DCK), an important enzyme for the salvage of deoxynucleotides, in the progression of pulmonary fibrosis. DCK expression was examined in the lungs of patients with IPF and mice exposed to bleomycin. The regulation of DCK expression by hypoxia was studied in vitro and the importance of DCK in experimental pulmonary fibrosis was examined using a DCK inhibitor and alveolar epithelial cell-specific knockout mice. DCK was elevated in hyperplastic alveolar epithelial cells of patients with IPF and in mice exposed to bleomycin. Increased DCK was localized to cells associated with hypoxia, and hypoxia directly induced DCK in alveolar epithelial cells in vitro. Hypoxia-induced DCK expression was abolished by silencing hypoxia-inducible factor 1α and treatment of bleomycin-exposed mice with a DCK inhibitor attenuated pulmonary fibrosis in association with decreased epithelial cell proliferation. Furthermore, DCK expression, and proliferation of epithelial cells and pulmonary fibrosis was attenuated in mice with conditional deletion of hypoxia-inducible factor 1α in the alveolar epithelium. Our findings suggest that the induction of DCK after hypoxia plays a role in the progression of pulmonary fibrosis by contributing to alveolar epithelial cell proliferation.

  16. Effects on mother and fetus of epidural and combined spinal-epidural techniques for labor analgesia Efeitos maternos e fetais da analgesia de parto pelas técnicas peridural e duplo bloqueio

    Directory of Open Access Journals (Sweden)

    Giane Nakamura

    2009-01-01

    Full Text Available OBJECTIVE: Epidural (EA and combined spinal-epidural (CSE techniques have both been utilized for labor analgesia. This study compared the effects on the mother and newborn of these techniques in labor analgesia and anesthesia. METHODS: Forty pregnant women received epidural analgesia with 15 mL of 0.125% ropivacaine (EA group and 5 µg of sufentanil plus 2.5mg bupivacaine in the subarachnoid space (CSE group. Pain intensity, sensory blockade level, latency time, motor block intensity, labor analgesia duration, epidural analgesia duration, maternal hypotension, and pruritus were evaluated. The newborns were evaluated by Apgar and the neurological and adaptive capacity score (NACS developed by Amiel-Tison. RESULTS: There were no significant statistical differences between groups for pain scores, latency time, sensory blockade level, and Apgar score. Motor block, labor analgesia duration, and epidural analgesia duration were greater in the CSE group, whose seven mothers had mild pruritus. The NACS were greater in the EA group after half, two, and 24 hours. Ninety five percent of EA group newborns and 60% of CSE group newborns were found to be neurologically healthy at the 24 hour examination. CONCLUSION: EA and CSE analgesia relieved maternal pain during obstetric analgesia, but CSE mothers had pruritus and a longer labor. Newborns of mothers who received epidural analgesia showed the best NACS.OBJETIVO: A peridural (AP e a técnica de duplo bloqueio (DB são utilizadas em analgesia para o trabalho de parto. Este estudo comparou os efeitos na mãe e no feto de ambas as técnicas em analgesia e anestesia para o parto. MÉTODOS: Quarenta parturientes ASA I e II receberam por via peridural 15 ml de ropivacaína a 0,125% (grupo AP e 5 µg de sufentanil com 2,5 mg bupivacaína por via subaracnóidea (grupo DB. Foram avaliados: intensidade de dor, altura do bloqueio sensitivo, tempo de latência, bloqueio motor, duração da analgesia de parto, tempo

  17. Protein S is protective in pulmonary fibrosis.

    Science.gov (United States)

    Urawa, M; Kobayashi, T; D'Alessandro-Gabazza, C N; Fujimoto, H; Toda, M; Roeen, Z; Hinneh, J A; Yasuma, T; Takei, Y; Taguchi, O; Gabazza, E C

    2016-08-01

    Essentials Epithelial cell apoptosis is critical in the pathogenesis of idiopathic pulmonary fibrosis. Protein S, a circulating anticoagulant, inhibited apoptosis of lung epithelial cells. Overexpression of protein S in lung cells reduced bleomycin-induced pulmonary fibrosis. Intranasal therapy with exogenous protein S ameliorated bleomycin-induced pulmonary fibrosis. Background Pulmonary fibrosis is the terminal stage of interstitial lung diseases, some of them being incurable and of unknown etiology. Apoptosis plays a critical role in lung fibrogenesis. Protein S is a plasma anticoagulant with potent antiapoptotic activity. The role of protein S in pulmonary fibrosis is unknown. Objectives To evaluate the clinical relevance of protein S and its protective role in pulmonary fibrosis. Methods and Results The circulating level of protein S was measured in patients with pulmonary fibrosis and controls by the use of enzyme immunoassays. Pulmonary fibrosis was induced with bleomycin in transgenic mice overexpressing human protein S and wild-type mice, and exogenous protein S or vehicle was administered to wild-type mice; fibrosis was then compared in both models. Patients with pulmonary fibrosis had reduced circulating levels of protein S as compared with controls. Inflammatory changes, the levels of profibrotic cytokines, fibrosis score, hydroxyproline content in the lungs and oxygen desaturation were significantly reduced in protein S-transgenic mice as compared with wild-type mice. Wild-type mice treated with exogenous protein S showed significant decreases in the levels of inflammatory and profibrotic markers and fibrosis in the lungs as compared with untreated control mice. After bleomycin infusion, mice overexpressing human protein S showed significantly low caspase-3 activity, enhanced expression of antiapoptotic molecules and enhanced Akt and Axl kinase phosphorylation as compared with wild-type counterparts. Protein S also inhibited apoptosis of alveolar

  18. Bloqueio peridural caudal: técnica anestésica de uso exclusivo em crianças? É possível sua realização em adultos? Qual o papel do ultrassom nesse contexto?

    Directory of Open Access Journals (Sweden)

    Ilana Esquenazi Najman

    2011-02-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O bloqueio peridural caudal é a mais popular entre todas as técnicas de anestesia regional em crianças. Com o avanço da idade, apenas a relativa dificuldade em localizar o hiato sacral limita seu uso. Entretanto, em adultos a técnica vem sendo largamente utilizada para controle de dor crônica com o auxílio da fluoroscopia. Assim, a habilidade em localizar o hiato e definir as variações anatômicas é o principal fator determinante do sucesso e segurança na execução do bloqueio peridural pela via caudal. Nesse contexto, o ultrassom vem ganhando espaço como guia para a realização do bloqueio caudal. O objetivo desta revisão foi elucidar o papel do ultrassom na anestesia caudal, além de demonstrar que o bloqueio caudal, muito utilizado em crianças, também é útil e pode ser usado em adultos. CONTEÚDO: Uma revisão literária sobre a anatomia da região sacral e da técnica anestésica necessária para a realização adequada do bloqueio caudal foi promovida. Além disso, artigos recentes sobre estudos realizados com bloqueios peridurais caudais guiados por ultrassom tanto em crianças quanto em adultos também foram incluídos. CONCLUSÕES: O ultrassom, apesar de suas limitações, pode ser útil como ferramenta adjuvante no posicionamento da agulha no espaço caudal. Permite a fácil identificação da anatomia sacral, além de visualização da injeção, em tempo real. Sua natureza portátil, não invasiva e livre de exposição à radiação faz dele uma tecnologia atrativa na sala operatória, principalmente na emergência de casos difíceis. Entretanto, como seu uso em bloqueios centrais do neuroeixo ainda é muito primitivo, é necessário que mais pesquisas sejam feitas para se consagre como técnica de rotina na prática anestésica.

  19. [Historical compilation of cystic fibrosis].

    Science.gov (United States)

    Navarro, Salvador

    2016-01-01

    Cystic fibrosis is the most common life-shortening recessively inherited disorder in the Caucasian population. The genetic mutation that most frequently provokes cystic fibrosis (ΔF508) appeared at least 53,000years ago. For many centuries, the disease was thought to be related to witchcraft and the "evil eye" and it was only in 1938 that Dorothy H. Andersen characterized this disorder and suspected its genetic origin. The present article reviews the pathological discoveries and diagnostic and therapeutic advances made in the last 75 years. The review ends with some considerations for the future. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  20. Epidemiology of idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Ley B

    2013-11-01

    Full Text Available Brett Ley, Harold R Collard Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California San Francisco, San Francisco, California, USA Abstract: Idiopathic pulmonary fibrosis is a chronic fibrotic lung disease of unknown cause that occurs in adults and has a poor prognosis. Its epidemiology has been difficult to study because of its rarity and evolution in diagnostic and coding practices. Though uncommon, it is likely underappreciated both in terms of its occurrence (ie, incidence, prevalence and public health impact (ie, health care costs and resource utilization. Incidence and mortality appear to be on the rise, and prevalence is expected to increase with the aging population. Potential risk factors include occupational and environmental exposures, tobacco smoking, gastroesophageal reflux, and genetic factors. An accurate understanding of its epidemiology is important, especially as novel therapies are emerging. Keywords: idiopathic pulmonary fibrosis, epidemiology, incidence, prevalence, mortality, risk factors

  1. Pathogenesis of oral submucous fibrosis

    Directory of Open Access Journals (Sweden)

    Saba Khan

    2012-01-01

    Full Text Available Data from recent epidemiological studies provide overwhelming evidence that areca nut is the main etiological factor for oral submucous fibrosis (OSF. It is logical to hypothesize that the increased collagen synthesis or reduced collagen degradation is the possible mechanism in the development of the disease. There are numerous biological pathways involved in the above processes and it is likely that the normal regulatory mechanisms are either down regulated or up regulated at different stages of the disease. The copper content of areca nut is high and the possible role of copper as a mediator of fibrosis is supported by the demonstration of the up regulation of lysyl oxidase in OSMF biopsies. The aim of this article is to emphasize that the incorporation of copper into the areca nut is through the Bordeaux mixture, which is sprayed as a fungicide on areca plantations in regions with scheduled monsoons and of which copper sulfate is an important constituent.

  2. [Morbus Ormond (idiopatic retroperitoneal fibrosis)].

    Science.gov (United States)

    Michaligová, A; Plank, L; Jezíková, A; Manka, V; Makovický, P; Mokán, M

    2011-05-01

    Idiopathic retroperitoneal fibrosis (IRF) is a rare condition characterized by the development of fibrotic tissue around the abdominal aorta and iliac arteries and often involves structures as ureters and the inferior vena cava. The age at onset of signs and symptoms is between 40-60 years, males predominane over females. In most cases the clinical manifestation is presented as compressive syndrom of ureters, therefore the first known cases were described by urologists. In this report we present the case of 37-years old male examinated for persistent fever about 38 degrees C and high inflammatory activity in spite of empiric antibiotic therapy. Positron emission tomography (PET) showed locality of high metabolic activity of fluorodeoxyglucose with maximum paraaortal left. Microscopic examination of extracted mass showed presence of fibrous and inflammatory components. With clinical presentation, imaging and histological findings we made out the diagnosis of idiopathic retroperitoneal fibrosis--morbus Ormond.

  3. Infection Control in Cystic Fibrosis

    OpenAIRE

    Saiman, Lisa; Siegel, Jane

    2004-01-01

    Over the past 20 years there has been a greater interest in infection control in cystic fibrosis (CF) as patient-to-patient transmission of pathogens has been increasingly demonstrated in this unique patient population. The CF Foundation sponsored a consensus conference to craft recommendations for infection control practices for CF care providers. This review provides a summary of the literature addressing infection control in CF. Burkholderia cepacia complex, Pseudomonas aeruginosa, and Sta...

  4. Epigenomics of idiopathic pulmonary fibrosis

    OpenAIRE

    Yang, Ivana V

    2012-01-01

    Idiopathic pulmonary fibrosis (IPF) is a complex lung disease of unknown etiology. Development of IPF is influenced by both genetic and environmental factors. Gene-expression profiling studies have taught us quite a bit about the biology of this fatal disease, but epigenetic marks may be the missing link that connects the environmental exposure in genetically predisposed individuals to transcriptome changes associated with the development of IPF. This review will begin with an introduction to...

  5. Pseudomembranous colitis in cystic fibrosis.

    Science.gov (United States)

    Nagakumar, Prasad

    2013-05-01

    Cystic fibrosis (CF) patients may require frequent courses of antibiotics and repeated hospital admissions. Although children with CF have high carriage rate for C.difficile, they rarely develop colitis. Pseudomembranous colitis is more common in adult post lung transplant CF patients. Although rare, paseudomembranous colitis should be considered in CF patients presenting with abdominal symptoms even in the absence of diarrhoea. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Idiopathic pulmonary fibrosis: treatment update.

    LENUS (Irish Health Repository)

    O'Connell, Oisin J

    2011-11-01

    Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias. Despite multiple recent clinical trials, there is no strong evidence supporting a survival advantage for any agent in the management of patients with IPF. The limited effectiveness of current treatment regimes has led to a search for novel therapies including antifibrotic strategies. This article reviews the evidence supporting the treatments currently used in the management of IPF.

  7. Lactate in cystic fibrosis sputum

    DEFF Research Database (Denmark)

    Bensel, Tobias; Stotz, Martin; Borneff-Lipp, Marianne

    2011-01-01

    Antibiotic therapy is thought to improve lung function in patients with cystic fibrosis (CF) by decreasing neutrophil-derived inflammation. We investigated the origin and clinical significance of lactate in the chronically inflamed CF lung. Methods Lactate was measured in sputa of 18 exacerbated...... and 25 stable CF patients via spectrophotometry and gaschromatography. Lung function was assessed via spirometry. Seven patients with chronic obstructive pulmonary disease (COPD) and three patients with acute lung inflammation served as control groups. Neutrophil and bacterial lactate production...

  8. A case of cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Maria Alice Monti

    2009-09-01

    Full Text Available As the expected survival improves for patients with cystic fibrosis (CF, there is a growing population of adults with this disease. We describe a case of a 33-year-old woman with CF presenting with recurrent pancreatitis, malnutrition, borderline sweat test and respiratory diseases. The case report underlines the importance of diagnosis and management of CF in adults, and the important role played by the Family Physician in developing an adult care program.

  9. Recommendations for quality improvement in genetic testing for cystic fibrosis European Concerted Action on Cystic Fibrosis

    NARCIS (Netherlands)

    Dequeker, E; Cuppens, H; Dodge, J; Estivill, [No Value; Goossens, M; Pignatti, PF; Scheffer, H; Schwartz, M; Schwarz, M; Tummler, B; Cassiman, JJ

    These recommendations for quality improvement of cystic fibrosis genetic diagnostic testing provide general guidelines for the molecular genetic testing of cystic fibrosis in patients/individuals. General strategies for testing as well as guidelines for laboratory procedures, internal and external

  10. Oral submucous fibrosis: an update

    Directory of Open Access Journals (Sweden)

    Wollina U

    2015-04-01

    Full Text Available Uwe Wollina,1 Shyam B Verma,2 Fareedi Mukram Ali,3 Kishor Patil4 1Department of Dermatology and Allergology, Academic Teaching Hospital Dresden-Friedrichstadt, Dresden, Germany; 2Nirvana Skin Clinic, Vadodara, Gujarat, India; 3Departments of Oral and Maxillofacial Surgery, SMBT Dental College, Sangamner, Maharashtra, India; 4Departments of Oral Pathology and Microbiology, SMBT Dental College, Sangamner, Maharashtra, India Abstract: Oral submucous fibrosis (OSF is a premalignant condition caused by betel chewing. It is very common in Southeast Asia but has started to spread to Europe and North America. OSF can lead to squamous cell carcinoma, a risk that is further increased by concomitant tobacco consumption. OSF is a diagnosis based on clinical symptoms and confirmation by histopathology. Hypovascularity leading to blanching of the oral mucosa, staining of teeth and gingiva, and trismus are major symptoms. Major constituents of betel quid are arecoline from betel nuts and copper, which are responsible for fibroblast dysfunction and fibrosis. A variety of extracellular and intracellular signaling pathways might be involved. Treatment of OSF is difficult, as not many large, randomized controlled trials have been conducted. The principal actions of drug therapy include antifibrotic, anti-inflammatory, and antioxygen radical mechanisms. Potential new drugs are on the horizon. Surgery may be necessary in advanced cases of trismus. Prevention is most important, as no healing can be achieved with available treatments. Keywords: betel nut, betel quid, oral disease, squamous cell carcinoma, tobacco, fibrosis

  11. Biomarkers in Paediatric Cystic Fibrosis Lung Disease.

    Science.gov (United States)

    Ramsey, Kathryn A; Schultz, André; Stick, Stephen M

    2015-09-01

    Biomarkers in cystic fibrosis are used i. for the measurement of cystic fibrosis transmembrane regulator function in order to diagnose cystic fibrosis, and ii. to assess aspects of lung disease severity (e.g. inflammation, infection). Effective biomarkers can aid disease monitoring and contribute to the development of new therapies. The tests of cystic fibrosis transmembrane regulator function each have unique strengths and weaknesses, and biomarkers of inflammation, infection and tissue destruction have the potential to enhance the management of cystic fibrosis through the early detection of disease processes. The development of biomarkers of cystic fibrosis lung disease, in particular airway inflammation and infection, is influenced by the challenges of obtaining relevant samples from infants and children for whom early detection and treatment of disease might have the greatest long term benefits. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Mast Cells: Key Contributors to Cardiac Fibrosis

    Directory of Open Access Journals (Sweden)

    Scott P. Levick

    2018-01-01

    Full Text Available Historically, increased numbers of mast cells have been associated with fibrosis in numerous cardiac pathologies, implicating mast cells in the development of cardiac fibrosis. Subsequently, several approaches have been utilised to demonstrate a causal role for mast cells in animal models of cardiac fibrosis including mast cell stabilising compounds, rodents deficient in mast cells, and inhibition of the actions of mast cell-specific proteases such as chymase and tryptase. Whilst most evidence supports a pro-fibrotic role for mast cells, there is evidence that in some settings these cells can oppose fibrosis. A major gap in our current understanding of cardiac mast cell function is identification of the stimuli that activate these cells causing them to promote a pro-fibrotic environment. This review will present the evidence linking mast cells to cardiac fibrosis, as well as discuss the major questions that remain in understanding how mast cells contribute to cardiac fibrosis.

  13. Endomyocardial fibrosis. Problems in differential diagnosis.

    Science.gov (United States)

    Falase, A O; Kolawole, T M; Lagundoye, S B

    1976-04-01

    The clinical and angiographic findings in 5 consecutive patients with congestive cardiac failure are presented to illustrate the pitfalls in the clinical diagnosis of endomyocardial fibrosis. In one patient the clinical diagnosis was confirmed at angiography while another patient who had angiographic evidence of early right ventricular endomyocardial fibrosis was diagnosed clinically as mitral stenosis. In 2 patients the clinical diagnosis was erroneous, there being no evidence of endomyocardial fibrosis on angiography. The fifth patient, who had angiographic evidence of idiopathic cardiomegaly, was diagnosed clinically as either idiopathic cardiomegaly or advanced left ventricular endomyocardial fibrosis. In tropical countries, where endomyocardial fibrosis, rheumatic heart disease, and idiopathic cardiomegaly are common, accurate clinical diagnosis of endomyocardial fibrosis is often difficult and angiographic studies are essential for confirmation.

  14. Oral submucous fibrosis and its dermatological relation

    OpenAIRE

    Fareedi Mukram Ali; Ashok Patil; Kishor Patil; M C Prasant

    2014-01-01

    Oral submucous fibrosis is a chronic insidious disease and is well-recognized as a premalignant condition. It is a collagen related disorder associated with betel quid chewing and characterized by progressive hyalinization of the submucosa. The oral submucous fibrosis needs to be differentiated from scleroderma showing oral manifestations, as these diseases have different pathogenesis and prognostic aspects. The patients of oral submucous fibrosis can approach the dermatologist. The aim of th...

  15. Liver fibrosis markers in alcoholic liver disease.

    Science.gov (United States)

    Chrostek, Lech; Panasiuk, Anatol

    2014-07-07

    Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.

  16. Liver fibrosis markers in alcoholic liver disease

    OpenAIRE

    Chrostek, Lech; Panasiuk, Anatol

    2014-01-01

    Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum mark...

  17. Secondary Retroperitoneal Fibrosis Associated with Generalized Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Barbullushi Myftar

    1999-01-01

    Full Text Available Retroperitoneal fibrosis is an uncommon disease that often presents in a subtle manner. Only a few cases of the combined association of generalized atherosclerosis and retroperitoneal fibrosis are reported in the recent literature, supporting the view that the condition is probably an autoimmune periaortitis. We describe a typical case of retroperitoneal fibrosis associated with generalized atherosclerosis with clinical presentation of progressive renal insufficiency, and claudication from arterial compromise.

  18. Secondary retroperitoneal fibrosis associated with generalized atherosclerosis.

    Science.gov (United States)

    Barbullushi, M; Pasko, N; Bezhani, E; Duraku, A; Rusi, R; Hoti, K; Bakalli, V; Idrizi, A

    1999-01-01

    Retroperitoneal fibrosis is an uncommon disease that often presents in a subtle manner. Only a few cases of the combined association of generalized atherosclerosis and retroperitoneal fibrosis are reported in the recent literature, supporting the view that the condition is probably an autoimmune periaortitis. We describe a typical case of retroperitoneal fibrosis associated with generalized atherosclerosis with clinical presentation of progressive renal insufficiency, and claudication from arterial compromise.

  19. Hyperplasia of elastic tissue in hepatic schistosomal fibrosis

    Directory of Open Access Journals (Sweden)

    Zilton A. Andrade

    1991-12-01

    Full Text Available Elastic tissue hyperplasia, revealed by means of histological, immunocytochemical and ultrastructural methods, appeared as a prominent change in surgical liver biopsies taken from 61 patients with schistosomal periportal and septal fibrosis. Such hyperplasia was absent in ecperimental murine schistosomiasis, including mice with "pipe-stem" fibrosis. Displaced connective tissue cells in periportal areas, such as smooth muscle cells, more frequently observed in human material, could be the site of excessive elastin synthesis, and could explain the differences observed in human and experimental materials. Elastic tissue, sometimes represented by its microfibrillar components, also appeared to be more condensed in areas of matrix (collagen degradation, suggesting a participation of this tissue in the remodelling of the extracellular matrix. By its rectratile properties elastic tissue hyperplasia in hepatic schistosomiasis can cause vascular narrowing and thus play a role in the pathogenesis of portal hypeertension.

  20. Therapeutic Potential of Polyphenols in Cardiac Fibrosis

    Directory of Open Access Journals (Sweden)

    Ning Zhang

    2018-02-01

    Full Text Available Cardiac fibrosis, in response to injury and stress, is central to a broad constellation of cardiovascular diseases. Fibrosis decreases myocardial wall compliance due to extracellular matrix (ECM accumulation, leading to impaired systolic and diastolic function and causing arrhythmogenesis. Although some conventional drugs, such as β-blockers and renin-angiotensin-aldosterone system (RAAS inhibitors, have been shown to alleviate cardiac fibrosis in clinical trials, these traditional therapies do not tend to target all the fibrosis-associated mechanisms, and do not hamper the progression of cardiac fibrosis in patients with heart failure. Polyphenols are present in vegetables, fruits, and beverages and had been proposed as attenuators of cardiac fibrosis in different models of cardiovascular diseases. Together with results found in the literature, we can show that some polyphenols exert anti-fibrotic and myocardial protective effects by mediating inflammation, oxidative stress, and fibrotic molecular signals. This review considers an overview of the mechanisms of cardiac fibrosis, illustrates their involvement in different animal models of cardiac fibrosis treated with some polyphenols and projects the future direction and therapeutic potential of polyphenols on cardiac fibrosis.

  1. Cystic Fibrosis Research | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... please turn Javascript on. Feature: Steady Advances Against Cystic Fibrosis Cystic Fibrosis Research Past Issues / Fall 2012 Table of Contents "Remarkable strides in cystic fibrosis research over the past two decades have culminated ...

  2. [RETRACTED ARTICLE] Characteristics of liver fibrosis with different etiologies using a fully quantitative fibrosis assessment tool

    Directory of Open Access Journals (Sweden)

    Q. Wu

    Full Text Available This study aimed to test the diagnostic performance of a fully quantitative fibrosis assessment tool for liver fibrosis in patients with chronic hepatitis B (CHB, primary biliary cirrhosis (PBC and non-alcoholic steatohepatitis (NASH. A total of 117 patients with liver fibrosis were included in this study, including 50 patients with CHB, 49 patients with PBC and 18 patients with NASH. All patients underwent liver biopsy (LB. Fibrosis stages were assessed by two experienced pathologists. Histopathological images of LB slices were processed by second harmonic generation (SHG/two-photon excited fluorescence (TPEF microscopy without staining, a system called qFibrosis (quantitative fibrosis system. Altogether 101 quantitative features of the SHG/TPEF images were acquired. The parameters of aggregated collagen in portal, septal and fibrillar areas increased significantly with stages of liver fibrosis in PBC and CHB (P0.05. There was a significant correlation between parameters of aggregated collagen in portal, septal and fibrillar areas and stages of liver fibrosis from CHB and PBC (P0.05. There was no significant correlation between NASH parameters and stages of fibrosis (P>0.05. For CHB and PBC patients, the highest correlation was between septal parameters and fibrosis stages, the second highest was between portal parameters and fibrosis stages and the lowest correlation was between fibrillar parameters and fibrosis stages. The correlation between the septal parameters of the PBC and stages is significantly higher than the parameters of the other two areas (P<0.05. The qFibrosis candidate parameters based on CHB were also applicable for quantitative analysis of liver fibrosis in PBC patients. Different parameters should be selected for liver fibrosis assessment in different stages of PBC compared with CHB.

  3. The Sociology and Entrenchment. A Cystic Fibrosis Test for Everyone?

    DEFF Research Database (Denmark)

    Koch, Lene; Stemerding, Dirk

    1994-01-01

    Socialmedicine, genetic screening, cystic fibrosis, ethics, political regulation, sociology of technology......Socialmedicine, genetic screening, cystic fibrosis, ethics, political regulation, sociology of technology...

  4. Irsogladine maleate ameliorates inflammation and fibrosis in mice with chronic colitis induced by dextran sulfate sodium.

    Science.gov (United States)

    Yamaguchi, Hana; Suzuki, Kenji; Nagata, Masaki; Kawase, Tomoyuki; Sukumaran, Vijayakumar; Thandavarayan, Rajarajan A; Kawauchi, Yusuke; Yokoyama, Junji; Tomita, Masayuki; Kawachi, Hiroshi; Watanabe, Kenichi; Yoneyama, Hiroyuki; Asakura, Hitoshi; Takagi, Ritsuo

    2012-06-01

    Intestinal fibrosis is a common and severe complication of inflammatory bowel disease (IBD), especially Crohn's disease (CD). To investigate the therapeutic approach to intestinal fibrosis, we have developed a mouse model of intestinal fibrosis by administering dextran sulfate sodium (DSS) and examining the effects of irsogladine maleate (IM) [2,4-diamino-6-(2,5-dichlorophenyl)-s-triazine maleate], which has been widely used as an antiulcer drug for gastric mucosa in Japan, on DDS-induced chronic colitis. In this experimental colitis lesion, several pathognomonic changes were found: increased deposition of collagen, increased number of profibrogenic mesenchymal cells such as fibroblasts (vimentin(+), α-SMA(-)) and myofibroblasts (vimentin(+), α-SMA(+)) in both mucosa and submucosa of the colon with infiltrating inflammatory cells, and increased mRNA expressions of collagen type I, transforming growth factor (TGF)-β, matrix metalloproteinase (MMP)-2, and tissue inhibitor of matrix metalloproteinase (TIMP)-1. When IM was administered intrarectally to this colitis, all these pathological changes were significantly decreased or suppressed, suggesting a potential adjunctive therapy for intestinal fibrosis. IM could consequently reduce fibrosis in DSS colitis by direct or indirect effect on profibrogenic factors or fibroblasts. Therefore, the precise effect of IM on intestinal fibrosis should be investigated further.

  5. Tregs promote the differentiation of Th17 cells in silica-induced lung fibrosis in mice.

    Directory of Open Access Journals (Sweden)

    Laiyu Song

    Full Text Available BACKGROUND: Silicosis is an occupational lung disease caused by inhalation of silica dust and characterized by lung inflammation and fibrosis. Previous study showed that Tregs regulate the process of silicosis by modulating the maintenance of immune homeostasis in the lung. Th17 cells share reciprocal developmental pathway with Tregs and play a pivotal role in the immunopathogenesis of many lung diseases by recruiting and activating neutrophils, but the regulatory function of Tregs on Th17 response in silica induced lung fibrosis remains to be explored. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the role of Th17 and IL-17 in the development of silicosis and their interaction with Tregs, Treg-depleted mice model was generated and exposed to silica to establish experimental model of silica-induced lung fibrosis. Here we showed that silica increased Th17 response in lung fibrosis. Tregs depletion enhanced the neutrophils accumulation and attenuated Th17 response in silica induced lung fibrosis. Both mRNA and protein results showed that Tregs exerted its modulatory function on Th17 cells and IL-17 by regulating TGF-β1 and IL-1β. CONCLUSION/SIGNIFICANCE: Our study suggested that Tregs could promote Th17 cells differentiation by regulating TGF-β1 and IL-1β in silica induced lung fibrosis of mice, which further the understanding of the progress of silicosis and provide a new insight in the regulatory mechanism of Th17 by Tregs in lung inflammation.

  6. Alveolar type II cell transplantation restores pulmonary surfactant protein levels in lung fibrosis.

    Science.gov (United States)

    Guillamat-Prats, Raquel; Gay-Jordi, Gemma; Xaubet, Antoni; Peinado, Victor I; Serrano-Mollar, Anna

    2014-07-01

    Alveolar Type II cell transplantation has been proposed as a cell therapy for the treatment of idiopathic pulmonary fibrosis. Its long-term benefits include repair of lung fibrosis, but its success partly depends on the restoration of lung homeostasis. Our aim was to evaluate surfactant protein restoration after alveolar Type II cell transplantation in an experimental model of bleomycin-induced lung fibrosis in rats. Lung fibrosis was induced by intratracheal instillation of bleomycin. Alveolar Type II cells were obtained from healthy animals and transplanted 14 days after bleomycin was administered. Furthermore, one group transplanted with alveolar macrophages and another group treated with surfactant were established to evaluate the specificity of the alveolar Type II cell transplantation. The animals were euthanized at 21 days after bleomycin instillation. Lung fibrosis was confirmed by a histologic study and an evaluation of the hydroxyproline content. Changes in surfactant proteins were evaluated by mRNA expression, Western blot and immunofluorescence studies. The group with alveolar Type II cell transplantation was the only one to show a reduction in the degree of lung fibrosis and a complete recovery to normal levels of surfactant proteins. One of the mechanisms involved in the beneficial effect of alveolar Type II cell transplantation is restoration of lung surfactant protein levels, which is required for proper respiratory function. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  7. Bloqueio peridural sacral: avaliação da duração da analgesia com o uso associado de lidocaína, fentanil e clonidina Bloqueo peridural sacral: evaluación de la duración de la analgesia con el uso asociado de lidocaína, fentanil y clonidina Epidural caudal block: evaluation of length of analgesia with the association of lidocaine, fentanyl and clonidine

    Directory of Open Access Journals (Sweden)

    Carlos Alberto de Souza Martins

    2004-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A associação de diferentes substâncias aos anestésicos locais é feita com o objetivo de melhorar a qualidade do bloqueio e prolongar a duração da analgesia. O objetivo deste trabalho foi comparar a eficácia da associação de clonidina, clonidina e fentanil e do fentanil à lidocaína, no tempo de analgesia pós-operatória. MÉTODO: O estudo envolveu 64 pacientes com idade igual ou superior a 23 anos, estado físico I ou II (ASA, escalados para cirurgia proctológica orificial, submetidos à anestesia peridural sacral. Os pacientes foram distribuídos em 4 grupos de 16: grupo I (lidocaína isolada, grupo II (lidocaína e fentanil, grupo III (lidocaína, fentanil e clonidina e grupo IV (lidocaína e clonidina. Foram comparadas as características dos bloqueios sensitivo e motor. RESULTADOS: Não houve diferença entre a latência, bem como no nível máximo de bloqueio entre os grupos. A ausência de bloqueio motor foi o resultado mais freqüente, encontrado em cerca de 64% dos pacientes. O intervalo de analgesia foi diferente entre os grupos, sendo mais significativo no grupo III. CONCLUSÕES: O uso da clonidina, associada ou não ao fentanil, prolongou o tempo de analgesia pós-operatória na anestesia peridural sacral com lidocaína.JUSTIFICATIVA Y OBJETIVOS: La asociación de diferentes substancias a los anestésicos locales es hecha con el objetivo de mejorar la cualidad del bloqueo y prolongar la duración de la analgesia. El objetivo de este trabajo fue comparar la eficacia de la asociación de clonidina, clonidina y fentanil y de fentanil a la lidocaína, en el tiempo de analgesia pós-operatoria. MÉTODO: El estudio envolvió 64 pacientes con edad igual o superior a 23 años, estado físico I ó II (ASA, escalados para cirugía proctológica orificial, sometidos a anestesia peridural sacral. Los pacientes fueron distribuidos en 4 grupos de 16: grupo I (lidocaína aislada, grupo II (lidocaína y

  8. Comparação entre raquianestesia, bloqueio combinado raqui-peridural e raquianestesia contínua para cirurgias de quadril em pacientes idosos: estudo retrospectivo Comparación entre raquianestesia, bloqueo combinado raqui-peridural y raquianestesia continua para cirugías de cuadril en pacientes ancianos: estudio retrospectivo Comparison between spinal, combined spinal-epidural and continuous spinal anesthesias for hip surgeries in elderly patients: a retrospective study

    Directory of Open Access Journals (Sweden)

    Luiz Eduardo Imbelloni

    2002-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Diversas questões envolvem os estudos, as análises e o tamanho da amostra para que sejam demonstrados os benefícios da anestesia regional. Análise de dados geralmente custa menos e requer menos tempo quando comparado com amplo estudo aleatório controlado. Esta análise retrospectiva compara a raquianestesia contínua, o bloqueio combinado raqui-peridural e a raquianestesia simples para cirurgias de quadril em pacientes idosos durante quatro anos, para determinar as possíveis vantagens e desvantagens das três técnicas. MÉTODO: Foram avaliados 300 prontuários sendo que: 100 pacientes receberam raquianestesia simples (Grupo 1, 100 receberam bloqueio combinado raqui-peridural (Grupo 2 e 100 receberam raquianestesia contínua (Grupo 3 nos últimos quatro anos. Todos os bloqueios foram realizados em decúbito lateral esquerdo. Foram avaliados: sucesso de punção, nível da analgesia, bloqueio motor de membros inferiores, qualidade da anestesia, necessidade de complementação, incidência de falhas, parestesias, cefaléia pós-punção, alterações cardiovasculares, confusão mental e delírio, transfusão sangüínea e mortalidade. RESULTADOS: Não existiu diferença significativa entre os grupos em relação a idade, peso e sexo. Os pacientes do grupo 2 foram menores do que os do grupo 1 e 3. As doses utilizadas foram de 15,30 mg de bupivacaína no grupo 1; 23,68 mg no grupo 2 e 10,10 mg no grupo 3. Não foi encontrada diferença significativa (p JUSTIFICATIVA Y OBJETIVOS: Diversas cuestiones envuelven los estudios, las análisis y el tamaño de la muestra para que sean demostrados los beneficios de la anestesia regional. Las análisis de datos generalmente cuestan menos y requieren menos tiempo, cuando comparado con un amplio estudio aleatorio controlado. Esta análisis retrospectiva compara la raquianestesia continua, el bloqueo combinado raqui-peridural y la raquianestesia simple para cirugías de cuadril en

  9. Fibrosis endomiocárdica

    Directory of Open Access Journals (Sweden)

    Alejandro Villamil-Munévar

    2017-01-01

    Full Text Available La fibrosis endomiocárdica o endocarditis de Löffler es una patología de causa todavía desconocida, esta puede presentarse durante la evolución de diversas enfermedades de causa infecciosa, tumoral, autoinmune, medicamentos, etc. En muchos casos el presentar eosinofilia moderada (más de 1500 eosinófilos/microlitro por largos períodos de tiempo puede producir toxicidad en diferentes órganos, entre ellos el corazón, produciendo disfunción del mismo por infiltración directa lo cual daña el tejido y también por las proteínas encontradas en los gránulos, principalmente la proteína catiónica eosinofílica y la proteína básica mayor que tienen predilección por el tejido endocárdico, llevando a su destrucción celular, lo que se traducirá en engrosamiento y fibrosis del subendocardio. Estas alteraciones conllevan a la cardiomiopatía restrictiva, siendo la fibrosis endomiocárdica su principal causa. Se presenta el caso de un paciente masculino de 30 años de edad, que ingresa al hospital por un cuadro de falla cardiaca aguda con evidencia en el ecocardiograma de ingreso de un componente restrictivo biventricular, el cual en diferentes series se presenta hasta en el 51% de los casos. El paciente presentaba una enfermedad hematológica de base, donde la eosinofilia era persistente durante más de 6 meses.

  10. Update on nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Thomsen, Henrik S; Marckmann, Peter; Logager, Vibeke B

    2008-01-01

    Gadolinium-based contrast agents were for many years considered safe, but this is no longer the case. The least stable agents may trigger the development of nephrogenic systemic fibrosis (NSF), a generalized fibrotic disorder, in renal failure patients. The use of gadodiamide and gadopentetate...... dimeglumine is now contraindicated in Europe and Japan in patients who have a glomerular filtration rate less than 30 mL/min/1.73 m(2), including those on dialysis. The fear of NSF, however, should not lead to an enhanced MR imaging examination being denied when there is a good clinical indication to give...

  11. Outcome in cystic fibrosis liver disease.

    LENUS (Irish Health Repository)

    Rowland, Marion

    2011-01-01

    Evidence suggests that cystic fibrosis liver disease (CFLD) does not affect mortality or morbidity in patients with cystic fibrosis (CF). The importance of gender and age in outcome in CF makes selection of an appropriate comparison group central to the interpretation of any differences in mortality and morbidity in patients with CFLD.

  12. Laparoscopic cholecystectomy in adult cystic fibrosis.

    LENUS (Irish Health Repository)

    McGrath, D S

    2012-02-03

    Two female patients with Cystic Fibrosis, attending the Adult Regional Cystic Fibrosis centre at the Cork University Hospital, were investigated for upper abdominal pain and found to have gallstones at ultrasonography. Laparoscopic cholecystectomy was performed successfully and, without complication, in both patients.

  13. SWE elastography in assessment of liver fibrosis

    Directory of Open Access Journals (Sweden)

    Urszula Zaleska-Dorobisz

    2015-02-01

    Full Text Available Liver fibrosis is a relatively common consequence of chronic liver diseases, especially chronic viral hepatitis B and C. Biopsy still remains the gold standard in the assessment of liver fibrosis. However, due to its invasiveness and possible complications, less or even non-invasive methods are being developed, e.g. using biochemical parameters (Fibrotest or elastography. Elastography is a new diagnostic tool that aims to evaluate stiffness of the tissues. Elastography techniques that are used in the assessment of liver fibrosis are transient elastography (TE, acoustic radiation force impulse (ARFI and shear-wave elastography (SWE. SWE is a novel real-time two-dimensional elastography technique, which allows one to estimate stiffness quantitatively in kilopascals (kPa. Moreover, lapping elastography over regular B-mode allows precise choice of the region of interest. Therefore SWE creates the opportunity for accurate assessment of liver fibrosis. In this paper we describe processes leading to liver fibrosis as well as methods of liver fibrosis assessment, e.g. liver biopsy, biochemical tests or elastography. The main goal of this paper is to present the SWE technique, its role in liver fibrosis assessment and a short review of the most important clinical studies on SWE. We also present several examples of SWE examinations performed on patients with different stages of liver fibrosis – F0 to F4 on the METAVIR scale.

  14. HOME CARE IN CYSTIC-FIBROSIS PATIENTS

    NARCIS (Netherlands)

    VANAALDEREN, WMC; MANNES, GPM; BOSMA, ES; ROORDA, RJ; HEYMANS, HSA

    Intravenous antibiotics and enteral tube feeding at home for the treatment of pulmonary exacerbations and underweight condition in cystic fibrosis (CF) patients have become tools that are used in many cystic fibrosis centres, The experience with home care programmes from different countries is quite

  15. Ovarian Fibrosis: A Phenomenon of Concern

    Directory of Open Access Journals (Sweden)

    Feng Zhou

    2017-01-01

    Conclusions: Patients with ovarian fibrosis are susceptible to infertility and tend to have decreased responses to assisted fertility treatment. Thus, protection of ovarian function should be a priority for women who wish to reproduce when making therapeutic decisions about ovarian fibrosis-related diseases.

  16. Self-management education for cystic fibrosis.

    LENUS (Irish Health Repository)

    Savage, Eileen

    2011-01-01

    Self-management education may help patients with cystic fibrosis and their families to choose, monitor and adjust treatment requirements for their illness, and also to manage the effects of illness on their lives. Although self-management education interventions have been developed for cystic fibrosis, no previous systematic review of the evidence of effectiveness of these interventions has been conducted.

  17. Management of Fibrosis: The Mesenchymal Stromal Cells Breakthrough

    Directory of Open Access Journals (Sweden)

    Benoît Usunier

    2014-01-01

    Full Text Available Fibrosis is the endpoint of many chronic inflammatory diseases and is defined by an abnormal accumulation of extracellular matrix components. Despite its slow progression, it leads to organ malfunction. Fibrosis can affect almost any tissue. Due to its high frequency, in particular in the heart, lungs, liver, and kidneys, many studies have been conducted to find satisfactory treatments. Despite these efforts, current fibrosis management therapies either are insufficiently effective or induce severe adverse effects. In the light of these facts, innovative experimental therapies are being investigated. Among these, cell therapy is regarded as one of the best candidates. In particular, mesenchymal stromal cells (MSCs have great potential in the treatment of inflammatory diseases. The value of their immunomodulatory effects and their ability to act on profibrotic factors such as oxidative stress, hypoxia, and the transforming growth factor-β1 pathway has already been highlighted in preclinical and clinical studies. Furthermore, their propensity to act depending on the microenvironment surrounding them enhances their curative properties. In this paper, we review a large range of studies addressing the use of MSCs in the treatment of fibrotic diseases. The results reported here suggest that MSCs have antifibrotic potential for several organs.

  18. Ovarian senescence increases liver fibrosis in humans and zebrafish with steatosis

    Directory of Open Access Journals (Sweden)

    Elena Turola

    2015-09-01

    Full Text Available Contrasting data exist on the effect of gender and menopause on the susceptibility, development and liver damage progression in non-alcoholic fatty liver disease (NAFLD. Our aim was to assess whether menopause is associated with the severity of liver fibrosis in individuals with NAFLD and to explore the issue of ovarian senescence in experimental liver steatosis in zebrafish. In 244 females and age-matched males with biopsy-proven NAFLD, we assessed anthropometric, biochemical and metabolic features, including menopausal status (self-reported; liver biopsy was scored according to ‘The Pathology Committee of the NASH Clinical Research Network’. Young and old male and female zebrafish were fed for 24 weeks with a high-calorie diet. Weekly body mass index (BMI, histopathological examination and quantitative real-time PCR analysis on genes involved in lipid metabolism, inflammation and fibrosis were performed. In the entire cohort, at multivariate logistic regression, male gender [odds ratio (OR: 1.408, 95% confidence interval (95% CI: 0.779-2.542, P=0.25] vs women at reproductive age was not associated with F2-F4 fibrosis, whereas a trend was observed for menopause (OR: 1.752, 95% CI: 0.956-3.208, P=0.06. In women, menopause (OR: 2.717, 95% CI: 1.020-7.237, P=0.04 was independently associated with F2-F4 fibrosis. Similarly, in overfed zebrafish, old female fish with failing ovarian function [as demonstrated by extremely low circulating estradiol levels (1.4±0.1 pg/µl and prevailing presence of atretic follicles in the ovaries] developed massive steatosis and substantial fibrosis (comparable with that occurring in males, whereas young female fish developed less steatosis and were totally protected from the development of fibrosis. Ovarian senescence significantly increases the risk of fibrosis severity both in humans with NAFLD and in zebrafish with experimental steatosis.

  19. Age-Dependent Susceptibility to Pulmonary Fibrosis Is Associated with NLRP3 Inflammasome Activation.

    Science.gov (United States)

    Stout-Delgado, Heather W; Cho, Soo Jung; Chu, Sarah G; Mitzel, Dana N; Villalba, Julian; El-Chemaly, Souheil; Ryter, Stefan W; Choi, Augustine M K; Rosas, Ivan O

    2016-08-01

    Aging has been implicated in the development of pulmonary fibrosis, which has seen a sharp increase in incidence in those older than 50 years. Recent studies demonstrate a role for the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome and its regulated cytokines in experimental lung fibrosis. In this study, we tested the hypothesis that age-related NLRP3 inflammasome activation is an important predisposing factor in the development of pulmonary fibrosis. Briefly, young and aged wild-type and NLRP3(-/-) mice were subjected to bleomycin-induced lung injury. Pulmonary fibrosis was determined by histology and hydroxyproline accumulation. Bone marrow and alveolar macrophages were isolated from these mice. NLRP3 inflammasome activation was assessed by co-immunoprecipitation experiments. IL-1β and IL-18 production was measured by ELISA. The current study demonstrated that aged wild-type mice developed more lung fibrosis and exhibited increased morbidity and mortality after bleomycin-induced lung injury, when compared with young mice. Bleomycin-exposed aged NLRP3(-/-) mice had reduced fibrosis compared with their wild-type age-matched counterparts. Bone marrow-derived and alveolar macrophages from aged mice displayed higher levels of NLRP3 inflammasome activation and caspase-1-dependent IL-1β and IL-18 production, which was associated with altered mitochondrial function and increased production of reactive oxygen species. Our study demonstrated that age-dependent increases in alveolar macrophage mitochondrial reactive oxygen species production and NLRP3 inflammasome activation contribute to the development of experimental fibrosis.

  20. Oral submucous fibrosis: an update

    Science.gov (United States)

    Wollina, Uwe; Verma, Shyam B; Ali, Fareedi Mukram; Patil, Kishor

    2015-01-01

    Oral submucous fibrosis (OSF) is a premalignant condition caused by betel chewing. It is very common in Southeast Asia but has started to spread to Europe and North America. OSF can lead to squamous cell carcinoma, a risk that is further increased by concomitant tobacco consumption. OSF is a diagnosis based on clinical symptoms and confirmation by histopathology. Hypovascularity leading to blanching of the oral mucosa, staining of teeth and gingiva, and trismus are major symptoms. Major constituents of betel quid are arecoline from betel nuts and copper, which are responsible for fibroblast dysfunction and fibrosis. A variety of extracellular and intracellular signaling pathways might be involved. Treatment of OSF is difficult, as not many large, randomized controlled trials have been conducted. The principal actions of drug therapy include antifibrotic, anti-inflammatory, and antioxygen radical mechanisms. Potential new drugs are on the horizon. Surgery may be necessary in advanced cases of trismus. Prevention is most important, as no healing can be achieved with available treatments. PMID:25914554

  1. Nintedanib for Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Tepede, Abisola; Yogaratnam, Dinesh

    2017-01-01

    To review the pharmacology, safety, and efficacy of nintedanib for the treatment of idiopathic pulmonary fibrosis (IPF). A literature search was conducted via PubMed using the MeSH term "idiopathic pulmonary fibrosis" combined with the key word "nintedanib." Additional online searches using Google Scholar, Micromedex, and PubMed were performed to obtain prescribing and cost information. One phase II and 2 replicate phase III clinical trials that examined the safety and efficacy of nintedanib for IPF were identified. In patients with IPF, nintedanib was more effective than placebo in slowing the annual rate of decline in forced vital capacity (FVC). Improvements in mortality, quality of life, and risk of acute exacerbations have not been consistently demonstrated in clinical trials. Diarrhea was the most common adverse effect associated with nintedanib use. Outside of these clinical trials, there are limited data evaluating nintedanib for the treatment of IPF. Nintedanib is a safe and effective treatment option for patients with IPF. Nintedanib slows IPF disease progression by reducing the rate of decline in FVC. Reductions in mortality and acute exacerbations may be present in certain subgroups of patients, but these outcomes require further research. Future studies on nintedanib are needed to explore its use in more advanced stages of IPF, its long-term safety and efficacy, its value in combination with pirfenidone or other therapies for IPF, and its cost-effectiveness in clinical practice.

  2. Postinjection Muscle Fibrosis from Lupron

    Directory of Open Access Journals (Sweden)

    Erica Everest

    2015-01-01

    Full Text Available We describe the case of a 6.5-year-old girl with central precocious puberty (CPP, which signifies the onset of secondary sexual characteristics before the age of eight in females and the age of nine in males as a result of stimulation of the hypothalamic-pituitary-gonadal axis. Her case is likely related to her adoption, as children who are adopted internationally have much higher rates of CPP. She had left breast development at Tanner Stage 2, adult body odor, and mildly advanced bone age. In order to halt puberty and maximize adult height, she was prescribed a gonadotropin releasing hormone analog, the first line treatment for CPP. She was administered Lupron (leuprolide acetate Depot-Ped (3 months intramuscularly. After her second injection, she developed swelling and muscle pain at the injection site on her right thigh. She also reported an impaired ability to walk. She was diagnosed with muscle fibrosis. This is the first reported case of muscle fibrosis resulting from Lupron injection.

  3. Inhaled mannitol for cystic fibrosis.

    Science.gov (United States)

    Nolan, Sarah J; Thornton, Judith; Murray, Clare S; Dwyer, Tiffany

    2015-10-09

    Several agents are used to clear secretions from the airways of people with cystic fibrosis. Inhaled dry powder mannitol is now available in Australia and some countries in Europe. The exact mechanism of action of mannitol is unknown, but it increases mucociliary clearance. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. To assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences.Date of last search: 16 April 2015. All randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment. Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The searches identified nine separate studies (45 publications), of which four studies (36 publications) were included with a total of 667 participants, one study (only available as an abstract) is awaiting assessment and two studies are ongoing. Duration of treatment in the included studies ranged from two weeks to six months with open-label treatment for an additional six months in two of the studies. Three studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol); two of these were parallel studies with a similar design and data could be pooled, where data for a particular outcome and time point were available; also, one short

  4. Correlation between TIMP-1 expression and liver fibrosis in two rat liver fibrosis models.

    Science.gov (United States)

    Nie, Qing-He; Zhang, Ya-Fei; Xie, Yu-Mei; Luo, Xin-Dong; Shao, Bin; Li, Jun; Zhou, Yong-Xing

    2006-05-21

    To evaluate serum TIMP-1 level and the correlation between TIMP-1 expression and liver fibrosis in immune-induced and CCL4-induced liver fibrosis models in rats. Immune-induced and CCL4-induced liver fibrosis models were established by dexamethasone (0.01 mg) and CCL4 respectively. Serum TIMP-1 level was detected with ELISA, while histopathological grade of liver biopsy was evaluated. Spearman rank-correlation test was used to analyse the difference of the correlation between the TIMP-1 expression and hepatic fibrosis in the two fibrosis models. Furthermore, in situ hybridization was used to determine the expression difference of TIMP-1 mRNA in the two models. Positive correlation existed between serum TIMP-1 level of immune induced group and the histopathological stages of fibrosis liver of corresponding rats (Spearman rank-correlation test, r(s) = 0.812, P liver fibrosis model, the correlation between the serum TIMP-1 level and the severity of hepatic fibrosis was not statistically significant(Spearman rank-correlation test, r(s) = 0.229, P > 0.05). And compared with immune-induced model, the positive in situ hybridization signal of TIMP-1 mRNA was weaker, while the expression variation was higher in hepatic fibrosis of the same severity. The correlations between TIMP-1 expression and liver fibrosis in two rat liver fibrosis models are different. In immune-induced model, serum TIMP-1 level could reflect the severity of liver fibrosis, while in CCL4-induced model, the correlation between the serum TIMP-1 level and the severity of hepatic fibrosis was not statistically significant.

  5. Beyond TGFβ : Novel ways to target airway and parenchymal fibrosis

    NARCIS (Netherlands)

    Boorsma, C. E.; Dekkers, B. G. J.; van Dijk, E. M.; Kumawat, K.; Richardson, J.; Burgess, J.K.; John, A. E.

    2014-01-01

    Within the lungs, fibrosis can affect both the parenchyma and the airways. Fibrosis is a hallmark pathological change in the parenchyma in patients with idiopathic pulmonary fibrosis (IPF), whilst in asthma or chronic obstructive pulmonary disease (COPD) fibrosis is a component of the remodelling of

  6. Anestesia peridural contínua com ropivacaína a 0,2% associada a anestesia geral para cirurgia do abdômen superior em crianças Anestesia peridural contínua con ropivacaína a 0,2% asociada a anestesia general para cirugía del abdomen superior en niños Continuous epidural anesthesia with 0.2% ropivacaine associated to general anesthesia for upper abdominal surgery in children

    Directory of Open Access Journals (Sweden)

    Jyrson Guilherme Klamt

    2003-04-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Técnicas anestésicas têm sido empregadas em pacientes pediátricos para vários tipos de cirurgias, apresentando entre outras vantagens, a analgesia pós-operatória. O objetivo deste estudo foi avaliar o ritmo de infusão de propofol e a recuperação pós-anestésica de crianças submetidas à cirurgia abdominal alta sob anestesia peridural torácica com ropivacaína a 0,2%, associada à anestesia geral com propofol ou propofol mais sufentanil. MÉTODO: Vinte e seis crianças ASA I, II e III, com idades entre 0 e 4 anos, submetidas à cirurgia abdominal alta foram selecionadas para anestesia peridural torácica (T7-T8 com ropivacaína a 0,2% (1,5 ml.kg-1. Foram divididas aleatoriamente em dois grupos: Propofol (infusão de propofol e Sufentanil (infusão de propofol mais sufentanil 1 µg.kg-1. Os ritmos de infusões de propofol foram de 20 e 10 mg.kg-1.h-1 nos grupos Propofol e Sufentanil, respectivamente, ajustadas de modo a manter a pressão arterial cerca de 20% dos valores pré-indução e interrompidas 10 a 15 minutos antes do final estimado da cirurgia. A recuperação pós-anestésica foi avaliada através de uma escala modificada de Aldrete-Kroulik e a sedação avaliada através de uma escala de 5 pontos. RESULTADOS: Duas crianças de cada grupo foram excluídas por problemas técnicos. O ritmo de infusão foi significativamente menor no grupo Sufentanil em relação ao grupo Propofol durante 100 minutos após o início da cirurgia. Os tempos para extubação e transferência para a sala de recuperação pós-anestésica (SRPA foram significativamente menores no grupo Propofol, porém a intensidade e a duração da sedação foram maiores nesse grupo em relação ao grupo Sufentanil. Os escores de recuperação foram similares nos dois grupos. Após 3 horas na SRPA, todos pacientes haviam atingido os critérios para transferência para as enfermarias. Hipotensão arterial transitória foi observada em 2

  7. Viral infection drives tissue fibrosis in vitro

    Directory of Open Access Journals (Sweden)

    Andrea P. Malizia

    2008-04-01

    Full Text Available Idiopathic Pulmonary Fibrosis (IPF is a refractory and lethal interstitial lung disease characterized by loss of alveolar epithelial cells, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. In this study we utilised a microarray-based differential gene expression analysis strategy to identify molecular drivers of EBV associated with lung fibrosis. A549 cells and an alveolar epithelial cell line infected with EBV (VAAK were used to identify genes whose expression was altered by EBV reactivation. EBV reactivation by TGFbeta1 drives alterations in expression of non-canonical Wnt pathway mediators, implicating it in epithelial mesenchymal transition (EMT, the molecular event underpinning scar production in tissue fibrosis. Cell invasion, EMT correlated transcripts expression, GSK-3b and c-Jun activation were altered in response to non-canonical Wnt pathway regulation. The role of EBV in promoting fibrosis can be attenuated by antiviral strategies and inhibition of Wnt signalling. Activation of non-canonical Wnt signalling pathway by EBV in epithelial cells suggests a novel mechanism of tissue fibrosis. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  8. Biochemical markers of hepatic fibrosis.

    Science.gov (United States)

    Plebani, M; Burlina, A

    1991-06-01

    Most liver diseases lead to a pathobiochemical reaction termed liver fibrosis. This is a dynamic process implying different rates of progression or regression. Thus, histological examination of a liver biopsy is essential for a diagnosis but biochemical tests are necessary for assessing the activity of the process and monitoring its evolution. We review the most important constituents of liver connective tissue and the biochemical tests developed for evaluating liver fibrosis. The aminopeptide of type III procollagen is the most widely used parameter: two different radioimmunoassays have been developed with different affinities for the two circulating forms of the molecule. The determination of serum P3P reveals an elevation of blood levels both in acute and chronic liver diseases. In the first, serum P3P is an index of hepatic necrosis and inflammation which correlates with other biochemical parameters. In the second it is an index of active fibrogenesis. Moreover, in primary biliary cirrhosis this parameter is an independent prognostic variable and an important predictor of survival. Other immunoassays exist for different collagen cleavage products, but their clinical value is not established. Laminin and fibronectin are the principal structural glycoproteins in liver. Fibronectin determination does not seem to be of clinical value in liver disease. In contrast, serum laminin correlates with the severity of portal venous pressure in advanced liver disease. Its concentration parallels the severity of varices and may indicate the risk of bleeding. Hyaluronate is a high molecular weight polysaccharide, raised serum concentrations reflect both its increased synthesis by activated fibroblasts and its impaired catabolism by the liver. Thus, it may be useful for evaluating and monitoring the progression of chronic liver disease. The measurement of the activity of prolyl 4-hydroxylase as well as that of lysine oxidase and other enzymes has been proposed, but their

  9. Vitamin A supplementation for cystic fibrosis.

    Science.gov (United States)

    Bonifant, Catherine M; Shevill, Elizabeth; Chang, Anne B

    2014-05-14

    People with cystic fibrosis and pancreatic insufficiency are at risk of fat soluble vitamin deficiency as these vitamins (A, D, E and K) are co-absorbed with fat. Thus, some cystic fibrosis centres routinely administer these vitamins as supplements but the centres vary in their approach of addressing the possible development of deficiencies in these vitamins. Vitamin A deficiency causes predominantly eye and skin problems while supplementation of vitamin A to excessive levels may cause harm to the respiratory and skeletal systems in children. Thus a systematic review on vitamin A supplementation in people with cystic fibrosis would help guide clinical practice. To determine if vitamin A supplementation in children and adults with cystic fibrosis:1. reduces the frequency of vitamin A deficiency disorders;2. improves general and respiratory health;3. increases the frequency of vitamin A toxicity. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 07 April 2014. All randomised or quasi-randomised controlled trials comparing all preparations of oral vitamin A used as a supplement compared to either no supplementation (or placebo) at any dose and for any duration, in children or adults with cystic fibrosis (defined by sweat tests or genetic testing) with and without pancreatic insufficiency. No relevant studies for inclusion were identified in the search. No studies were included in this review. As there were no randomised or quasi-randomised controlled trials identified, we cannot draw any conclusions on the benefits (or otherwise) of regular administration of vitamin A in people with cystic fibrosis. Until further data are available, country or region specific guidelines on the use of

  10. Voice disorder in cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Bruna Mendes Lourenço

    Full Text Available Cystic fibrosis is a common autosomal recessive disorder with drastic respiratory symptoms, including shortness of breath and chronic cough. While most of cystic fibrosis treatment is dedicated to mitigating the effects of respiratory dysfunction, the potential effects of this disease on vocal parameters have not been systematically studied. We hypothesized that cystic fibrosis patients, given their characteristic respiratory disorders, would also present dysphonic symptoms. Given that voice disorders can severely impair quality of life, the identification of a potential cystic fibrosis-related dysphonia could be of great value for the clinical evaluation and treatment of this disease. We tested our hypothesis by measuring vocal parameters, using both objective physical measures and the GRBAS subjective evaluation method, in male and female cystic fibrosis patients undergoing conventional treatment and compared them to age and sex matched controls. We found that cystic fibrosis patients had a significantly lower vocal intensity and harmonic to noise ratio, as well as increased levels of jitter and shimmer. In addition, cystic fibrosis patients also showed higher scores of roughness, breathiness and asthenia, as well as a significantly altered general grade of dysphonia. When we segregated the results according to sex, we observed that, as a group, only female cystic fibrosis patients had significantly lower values of harmonic to noise ratio and an abnormal general grade of dysphonia in relation to matched controls, suggesting that cystic fibrosis exerts a more pronounced effect on vocal parameters of women in relation to men. Overall, the dysphonic characteristics of CF patients can be explained by dysfunctions in vocal fold movement and partial upper airway obstruction, potentially caused by the accumulation of mucus and chronic cough characteristic of CF symptomatology. Our results show that CF patients exhibit significant dysphonia and

  11. Noninvasive Biomarkers of Liver Fibrosis: An Overview

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    Hind I. Fallatah

    2014-01-01

    Full Text Available Chronic liver diseases of differing etiologies are among the leading causes of mortality and morbidity worldwide. Establishing accurate staging of liver disease is very important for enabling both therapeutic decisions and prognostic evaluations. A liver biopsy is considered the gold standard for assessing the stage of hepatic fibrosis, but it has many limitations. During the last decade, several noninvasive markers for assessing the stage of hepatic fibrosis have been developed. Some have been well validated and are comparable to liver biopsy. This paper will focus on the various noninvasive biochemical markers used to stage liver fibrosis.

  12. Transient elastography for liver fibrosis diagnosis

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Christensen, Peer Brehm; Weis, Nina

    2009-01-01

    Liver biopsy is considered the "golden standard" for assessment of hepatic fibrosis. However, the procedure has limitations because of inconvenience and rare but serious complications as bleeding. Furthermore, sampling errors are frequent, and interobserver variability often poses problems....... Recently, a modified ultrasound scanner (transient elastography) has been developed to assess fibrosis. The device measures liver elasticity, which correlates well with the degree of fibrosis. Studies have shown that transient elastography is more accurate in diagnosing cirrhosis than minor to moderate...... to be a valuable diagnostic procedure and follow-up of patients with chronic liver diseases....

  13. Combined Pulmonary Fibrosis and Emphysema Syndrome

    Science.gov (United States)

    Rounds, Sharon I. S.

    2012-01-01

    There is increasing clinical, radiologic, and pathologic recognition of the coexistence of emphysema and pulmonary fibrosis in the same patient, resulting in a clinical syndrome known as combined pulmonary fibrosis and emphysema (CPFE) that is characterized by dyspnea, upper-lobe emphysema, lower-lobe fibrosis, and abnormalities of gas exchange. This syndrome frequently is complicated by pulmonary hypertension, acute lung injury, and lung cancer. The CPFE syndrome typically occurs in male smokers, and the mortality associated with this condition, especially if pulmonary hypertension is present, is significant. In this review, we explore the current state of the literature and discuss etiologic factors and clinical characteristics of the CPFE syndrome. PMID:22215830

  14. Oral submucous fibrosis and its dermatological relation

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    Fareedi Mukram Ali

    2014-01-01

    Full Text Available Oral submucous fibrosis is a chronic insidious disease and is well-recognized as a premalignant condition. It is a collagen related disorder associated with betel quid chewing and characterized by progressive hyalinization of the submucosa. The oral submucous fibrosis needs to be differentiated from scleroderma showing oral manifestations, as these diseases have different pathogenesis and prognostic aspects. The patients of oral submucous fibrosis can approach the dermatologist. The aim of this article is to present concise overview of the disease and its dermatological relation.

  15. Oral submucous fibrosis and its dermatological relation

    Science.gov (United States)

    Ali, Fareedi Mukram; Patil, Ashok; Patil, Kishor; Prasant, M. C.

    2014-01-01

    Oral submucous fibrosis is a chronic insidious disease and is well-recognized as a premalignant condition. It is a collagen related disorder associated with betel quid chewing and characterized by progressive hyalinization of the submucosa. The oral submucous fibrosis needs to be differentiated from scleroderma showing oral manifestations, as these diseases have different pathogenesis and prognostic aspects. The patients of oral submucous fibrosis can approach the dermatologist. The aim of this article is to present concise overview of the disease and its dermatological relation. PMID:25165640

  16. Vitamin D deficiency as a risk factor for cystic fibrosis-related diabetes in the Scandinavian Cystic Fibrosis Nutritional Study

    DEFF Research Database (Denmark)

    Pincikova, T; Nilsson, Kristine Kahr; Moen, I E

    2011-01-01

    Many cystic fibrosis patients are vitamin D-insufficient. Cystic fibrosis-related diabetes is a major complication of cystic fibrosis. The literature suggests that vitamin D might possess certain glucose-lowering properties. We aimed to assess the relationship between vitamin D and cystic fibrosis...

  17. Cystic fibrosis-related diabetes

    DEFF Research Database (Denmark)

    Andersen, Henrik Ullits; Lanng, Susanne; Pressler, Tania

    2006-01-01

    OBJECTIVE: Cystic fibrosis (CF)-related diabetes has been regarded as a mild form of diabetes with a low risk of severe diabetes complications. The prevalence of CF-related diabetes increases with age, resulting in a 50% prevalence of diabetes at age 30 years. We sought to investigate whether...... microvascular complications in CF-related diabetes appear with a relevant frequency. RESEARCH DESIGN AND METHODS: Thirty-eight patients aged 30 (range 18-55) years with CF-related diabetes for 20 (0-31) years were screened for diabetes complications. Because of chronic pulmonary infections, the majority...... of diabetic retinopathy was found in patients with insulin-treated CF-related diabetes, stressing the need for a regular screening program as in type 1 diabetes. Severely impaired kidney function was common in lung transplant patients, probably secondary to cyclosporine treatment....

  18. Epigenomics of idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Yang, Ivana V

    2012-04-01

    Idiopathic pulmonary fibrosis (IPF) is a complex lung disease of unknown etiology. Development of IPF is influenced by both genetic and environmental factors. Gene-expression profiling studies have taught us quite a bit about the biology of this fatal disease, but epigenetic marks may be the missing link that connects the environmental exposure in genetically predisposed individuals to transcriptome changes associated with the development of IPF. This review will begin with an introduction to the disease, followed by brief summaries of studies of gene expression in IPF and epigenetic marks associated with exposures relevant to IPF. The majority of the discussion will focus on epigenetic studies conducted so far in IPF, the limitations, challenges nd future directions in this field.

  19. Pathogenesis of Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Wolters, Paul J.; Collard, Harold R.; Jones, Kirk D.

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated. PMID:24050627

  20. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Van Beneden, Katrien, E-mail: kvbenede@vub.ac.be [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Geers, Caroline [Department of Pathology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Pauwels, Marina [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Mannaerts, Inge [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Wissing, Karl M. [Department of Nephrology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Van den Branden, Christiane [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Grunsven, Leo A. van, E-mail: lvgrunsv@vub.ac.be [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium)

    2013-09-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation.

  1. Overexpression of Heme Oxygenase-1 Prevents Renal Interstitial Inflammation and Fibrosis Induced by Unilateral Ureter Obstruction.

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    Xiao Chen

    Full Text Available Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases. Many studies have demonstrated that heme oxygenase-1 (HO-1 is involved in diverse biological processes as a cytoprotective molecule, including anti-inflammatory, anti-oxidant, anti-apoptotic, antiproliferative, and immunomodulatory effects. However, the mechanisms of HO-1 prevention in renal interstitial fibrosis remain unknown. In this study, HO-1 transgenic (TG mice were employed to investigate the effect of HO-1 on renal fibrosis using a unilateral ureter obstruction (UUO model and to explore the potential mechanisms. We found that HO-1 was adaptively upregulated in kidneys of both TG and wild type (WT mice after UUO. The levels of HO-1 mRNA and protein were increased in TG mice compared with WT mice under normal conditions. HO-1 expression was further enhanced after UUO and remained high during the entire experimental process. Renal interstitial fibrosis in the TG group was significantly attenuated compared with that in the WT group after UUO. Moreover, overexpression of HO-1 inhibited the loss of peritubular capillaries. In addition, UUO-induced activation and proliferation of myofibroblasts were suppressed by HO-1 overexpression. Furthermore, HO-1 restrained tubulointerstitial infiltration of macrophages and regulated the secretion of inflammatory cytokines in UUO mice. We also found that high expression of HO-1 inhibited reactivation of Wnt/β-catenin signaling, which could play a crucial role in attenuating renal fibrosis. In conclusion, these data suggest that HO-1 prevents renal tubulointerstitial fibrosis possibly by regulating the inflammatory response and Wnt/β-catenin signaling. This study provides evidence that augmentation of HO-1 levels may be a therapeutic strategy against renal interstitial fibrosis.

  2. Galectin-3 Inhibition by a Small-Molecule Inhibitor Reduces Both Pathological Corneal Neovascularization and Fibrosis.

    Science.gov (United States)

    Chen, Wei-Sheng; Cao, Zhiyi; Leffler, Hakon; Nilsson, Ulf J; Panjwani, Noorjahan

    2017-01-01

    Corneal neovascularization and scarring commonly lead to significant vision loss. This study was designed to determine whether a small-molecule inhibitor of galectin-3 can inhibit both corneal angiogenesis and fibrosis in experimental mouse models. Animal models of silver nitrate cautery and alkaline burn were used to induce mouse corneal angiogenesis and fibrosis, respectively. Corneas were treated with the galectin-3 inhibitor, 33DFTG, or vehicle alone and were processed for whole-mount immunofluorescence staining and Western blot analysis to quantify the density of blood vessels and markers of fibrosis. In addition, human umbilical vein endothelial cells (HUVECs) and primary human corneal fibroblasts were used to analyze the role of galectin-3 in the process of angiogenesis and fibrosis in vitro. Robust angiogenesis was observed in silver nitrate-cauterized corneas on day 5 post injury, and markedly increased corneal opacification was demonstrated in alkaline burn-injured corneas on days 7 and 14 post injury. Treatment with the inhibitor substantially reduced corneal angiogenesis and opacification with a concomitant decrease in α-smooth muscle actin (α-SMA) expression and distribution. In vitro studies revealed that 33DFTG inhibited VEGF-A-induced HUVEC migration and sprouting without cytotoxic effects. The addition of exogenous galectin-3 to corneal fibroblasts in culture induced the expression of fibrosis-related proteins, including α-SMA and connective tissue growth factor. Our data provide proof of concept that targeting galectin-3 by the novel, small-molecule inhibitor, 33DFTG, ameliorates pathological corneal angiogenesis as well as fibrosis. These findings suggest a potential new therapeutic strategy for treating ocular disorders related to pathological angiogenesis and fibrosis.

  3. Modulation of the Unfolded Protein Response by Tauroursodeoxycholic Acid Counteracts Apoptotic Cell Death and Fibrosis in a Mouse Model for Secondary Biliary Liver Fibrosis.

    Science.gov (United States)

    Paridaens, Annelies; Raevens, Sarah; Devisscher, Lindsey; Bogaerts, Eliene; Verhelst, Xavier; Hoorens, Anne; Van Vlierberghe, Hans; van Grunsven, Leo A; Geerts, Anja; Colle, Isabelle

    2017-01-20

    The role of endoplasmic reticulum stress and the unfolded protein response (UPR) in cholestatic liver disease and fibrosis is not fully unraveled. Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, has been shown to reduce endoplasmic reticulum (ER) stress and counteract apoptosis in different pathologies. We aimed to investigate the therapeutic potential of TUDCA in experimental secondary biliary liver fibrosis in mice, induced by common bile duct ligation. The kinetics of the hepatic UPR and apoptosis during the development of biliary fibrosis was studied by measuring markers at six different timepoints post-surgery by qPCR and Western blot. Next, we investigated the therapeutic potential of TUDCA, 10 mg/kg/day in drinking water, on liver damage (AST/ALT levels) and fibrosis (Sirius red-staining), in both a preventive and therapeutic setting. Common bile duct ligation resulted in the increased protein expression of CCAAT/enhancer-binding protein homologous protein (CHOP) at all timepoints, along with upregulation of pro-apoptotic caspase 3 and 12, tumor necrosis factor receptor superfamily, member 1A (TNFRsf1a) and Fas-Associated protein with Death Domain (FADD) expression. Treatment with TUDCA led to a significant reduction of liver fibrosis, accompanied by a slight reduction of liver damage, decreased hepatic protein expression of CHOP and reduced gene and protein expression of pro-apoptotic markers. These data indicate that TUDCA exerts a beneficial effect on liver fibrosis in a model of cholestatic liver disease, and suggest that this effect might, at least in part, be attributed to decreased hepatic UPR signaling and apoptotic cell death.

  4. Cystic fibrosis-related bone disease.

    Science.gov (United States)

    Paccou, Julien; Fardellone, Patrice; Cortet, Bernard

    2013-11-01

    This review highlights recently published data on the pathophysiology, guidelines and treatment of cystic fibrosis (CF)-related bone disease. The exact role of the cystic fibrosis transmembrane conductance regulator (CFTR), specifically the ΔF508 allele, has been investigated in F508del-CFTR homozygous mice and the F508del-CFTR mutation may contribute to CF-related bone disease by slowing new bone formation. The European Cystic Fibrosis Society has issued guidelines for bone mineral density assessment, management of low-trauma fractures and bisphosphonate therapy. A systematic review based on meta-analyses reports that oral and intravenous bisphosphonates both improve bone mineral density in CF patients, but no data are available concerning the reduction of low-trauma fractures. European Cystic Fibrosis Society guidelines may help physicians to improve the management of CF-related bone disease.

  5. Transient elastography for liver fibrosis diagnosis

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Christensen, Peer Brehm; Weis, Nina

    2008-01-01

    Liver biopsy is considered the "golden standard" for assessment of hepatic fibrosis. However, the procedure has limitations because of inconvenience and rare but serious complications as bleeding. Furthermore, sampling errors are frequent, and interobserver variability often poses problems...

  6. Liver Fibrosis: Current Principles of Diagnosis

    Directory of Open Access Journals (Sweden)

    A.K. Duda

    2014-09-01

    Full Text Available Liver fibrosis — a natural consequence of almost all liver diseases of any origin. We are faced with a number of standard stereotype processes that take place in the liver tissue. Mostly it is the processes of chronic inflammation, which oppose the processes of liver tissue regeneration. The basis of imbalance between the processes of fibrosis and regeneration is an accumulation of extracellular matrix. Liver fibrosis in its development leads to liver cirrhosis, hepatocellular carcinoma, and the increase in morbidity rate is observed worldwide. Furthermore, the process is genetically determined, but modifiable factors play an important role in the progression of this disease. Current data indicate the possibility of reversible liver fibrosis.

  7. Nutrition in Cystic Fibrosis: Macro- and Micronutrients

    NARCIS (Netherlands)

    Oudshoorn, Johanna Hermiena

    2006-01-01

    Cystic fibrosis (CF) is the most common life-threatening autosomal recessive inherited disease in Caucasians, and is characterized by progressive lung disease, pancreatic insufficiency, malnutrition, hepatobiliary disease and elevated sweat electrolyte levels. The increased survival of CF patients

  8. Epigenetics and Liver FibrosisSummary

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    Eva Moran-Salvador

    2017-07-01

    Full Text Available Liver fibrosis arises because prolonged injury combined with excessive scar deposition within hepatic parenchyma arising from overactive wound healing response mediated by activated myofibroblasts. Fibrosis is the common end point for any type of chronic liver injury including alcoholic liver disease, nonalcoholic fatty liver disease, viral hepatitis, and cholestatic liver diseases. Although genetic influences are important, it is epigenetic mechanisms that have been shown to orchestrate many aspects of fibrogenesis in the liver. New discoveries in the field are leading toward the development of epigenetic biomarkers and targeted therapies. This review considers epigenetic mechanisms as well as recent advances in epigenetic programming in the context of hepatic fibrosis. Keywords: Liver Fibrosis, Epigenetics, DNA Methylation, Histone Modifications, Chronic Liver Disease

  9. Liver Transplantation for Cirrhosis in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    T Lamireau

    2006-01-01

    Full Text Available BACKGROUND: Liver disease is the third most common cause of death in children with cystic fibrosis (CF. Liver transplantation is an effective treatment in children with hepatic failure.

  10. Molecular and cellular mechanisms of pulmonary fibrosis

    Science.gov (United States)

    2012-01-01

    Pulmonary fibrosis is a chronic lung disease characterized by excessive accumulation of extracellular matrix (ECM) and remodeling of the lung architecture. Idiopathic pulmonary fibrosis is considered the most common and severe form of the disease, with a median survival of approximately three years and no proven effective therapy. Despite the fact that effective treatments are absent and the precise mechanisms that drive fibrosis in most patients remain incompletely understood, an extensive body of scientific literature regarding pulmonary fibrosis has accumulated over the past 35 years. In this review, we discuss three broad areas which have been explored that may be responsible for the combination of altered lung fibroblasts, loss of alveolar epithelial cells, and excessive accumulation of ECM: inflammation and immune mechanisms, oxidative stress and oxidative signaling, and procoagulant mechanisms. We discuss each of these processes separately to facilitate clarity, but certainly significant interplay will occur amongst these pathways in patients with this disease. PMID:22824096

  11. The impact of emphysema in pulmonary fibrosis

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    Vincent Cottin

    2013-06-01

    Full Text Available Several groups have described a syndrome in which idiopathic pulmonary fibrosis (IPF coexists with pulmonary emphysema. This comes as no surprise since both diseases are associated with a history of exposure to cigarette smoke. The syndrome of combined pulmonary fibrosis and emphysema (CPFE is characterised by upper lobe emphysema and lower lobe fibrosis. Physiological testing of these patients reveals preserved lung volume indices contrasted by markedly impaired diffusion capacity. The incidence of CPFE remains unknown but several case series suggest that this subgroup may comprise up to 35% of patients with IPF. CPFE is a strong determinant of associated pulmonary hypertension (PH. In addition, CPFE has major effects on measures of physiological function, exercise capacity and prognosis, and may affect the results of pulmonary fibrosis trials. Further studies are needed to ascertain the aetiology, morbidity, mortality and management of the CPFE syndrome, with or without PH, and to evaluate novel therapeutic options in CPFE.

  12. Pathogenesis of Type 2 Epithelial to Mesenchymal Transition (EMT in Renal and Hepatic Fibrosis

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    Anusha H. Tennakoon

    2015-12-01

    Full Text Available Epithelial to mesenchymal transition (EMT, particularly, type 2 EMT, is important in progressive renal and hepatic fibrosis. In this process, incompletely regenerated renal epithelia lose their epithelial characteristics and gain migratory mesenchymal qualities as myofibroblasts. In hepatic fibrosis (importantly, cirrhosis, the process also occurs in injured hepatocytes and hepatic progenitor cells (HPCs, as well as ductular reaction-related bile epithelia. Interestingly, the ductular reaction contributes partly to hepatocarcinogenesis of HPCs, and further, regenerating cholangiocytes after injury may be derived from hepatic stellate cells via mesenchymal to epithelia transition, a reverse phenomenon of type 2 EMT. Possible pathogenesis of type 2 EMT and its differences between renal and hepatic fibrosis are reviewed based on our experimental data.

  13. Mechanisms of fibrosis in acute liver failure.

    Science.gov (United States)

    He, Yingli; Jin, Li; Wang, Jing; Yan, Zhi; Chen, Tianyan; Zhao, Yingren

    2015-07-01

    Acute liver failure (ALF) is a condition with high mortality and morbidity. Fibrosis in chronic liver disease was extensively researched, whereas fibrosis and underlying mechanism in acute liver failure remains unclear. Hepatitis B virus related ALF patients were recruited to investigate if there was ongoing fibrosis by liver histology and liver stiffness measurement(LSM) analysis as well as fibrosis markers assay. Sera HMGB1 were kinetically detected in progression and remission stage of ALF. Hepatic stellate cell(HSC) activation by HMGB1 was explored by testing mRNA and protein level of α-SMA and collagen 1a1 by using qPCR and western blot. Autophagy induction by HMGB1 was explored by LC3-II conversion, autophagy flux and fluorescence. Firstly, ongoing fibrosis in progression stage of ALF was confirmed by histological analysis, LS measurement as well as fibrosis markers detection. HSC activation and autophagy induction in explanted liver tissue also revealed. Next, kinetic monitoring sera HMGB1 revealed elevated HMGB1 in progression stage of ALF vs HBsAg carrier, and drop back to base level in remission stage. Thirdly, rHMGB1 dose dependently activated HSCs, as indicated by increased mRNA and proteins level in α-SMA and collagen 1a1. Moreover, autophagy was induced in HSC treated with rHMGB1, as illustrated by increased LC3 lipidation, elevated autophagy flux and GFP-LC3 puncta. Acute liver failure is accompanied by ongoing fibrosis, HSC activation and autophagy induction. Increased HMGB1 activates HSC via autophagy induction. Those findings integrate HMGB1, HSCs activation, autophagy into a common framework that underlies the fibrosis in ALF. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

  14. Retroperitoneal fibrosis with normal intravenous urogram.

    OpenAIRE

    Creagh, F M; Stone, T; Stephenson, T P; Lazarus, J H

    1985-01-01

    A 58 year old male presented with a two week history of low back pain and malaise. The intravenous urogram (IVU) at presentation was normal but within three months he had developed renal failure with bilateral ureteric obstruction on repeat IVU. Primary retroperitoneal fibrosis was confirmed at operation. This case demonstrates that retroperitoneal fibrosis may progress rapidly to renal failure within a few months of the first symptoms. In addition, the IVU may be normal in the early stages o...

  15. Chronic hepatitis C and liver fibrosis

    OpenAIRE

    Sebastiani, Giada; Gkouvatsos, Konstantinos; Pantopoulos, Kostas

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the nex...

  16. Serum Biochemical Markers of Liver Fibrosis

    OpenAIRE

    Setiabudi, Irwan

    2006-01-01

    Progressive liver fibrosis with development of cirrhosis is a feature of almost all chronic liver diseases. Carriers of hepatitis B and C virus are at increased risk of developing cirrhosis, hepatic decompensation/insufficiency, hemorrhage, and hepatocellular carcinoma (HCC). Therefore, periodic evaluations of these patients are necessary. Fibrosis is deleterious but variable consequence of chronic inflammation. It is characterized by deposition of extra cellular matrix component leading to d...

  17. Chemoprotective effect of omega-3 fatty acids on thioacetamide induced hepatic fibrosis in male rats.

    Science.gov (United States)

    Al-Attar, Atef M; Al-Rethea, Hayfa A

    2017-05-01

    The current study was designed to investigate the possible protective effect of omega-3 fatty acids from fish oil on hepatic fibrosis induced by thioacetamide (TAA) in male rats. The experimental animals were divided into four groups. The first group was received saline solution and served as control. The second group was given 250 mg/kg body weight of TAA. The third group was treated with omega-3 fatty acids and TAA. The fourth group was given saline solution and supplemented with omega-3 fatty acids. Treatment of rats with TAA for three and six weeks resulted in a significant decrease in body weight gain, while the value of liver/body weight ratio was statistically increased. Furthermore, the levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase and total bilirubin were significantly increased. After three weeks of exposure to only TAA, liver sections showed an abnormal morphology characterized by noticeable fibrosis with the extracellular matrix collagen contents and damage of liver cells' structure. Liver sections from rats treated with only TAA for six weeks revealed an obvious increase in extracellular matrix collagen content and bridging fibrosis. Treating TAA-intoxicated rats with omega-3 fatty acids significantly attenuated the severe physiological and histopathological changes. Finally, the present investigation suggests that omega-3 fatty acids could act against hepatic fibrosis induced by TAA due to its antioxidant properties, thus supporting its use in hepatic fibrosis therapy.

  18. Acute rejection after kidney transplantation promotes graft fibrosis with elevated adenosine level in rat.

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    Mingliang Li

    Full Text Available Chronic allograft nephropathy is a worldwide issue with the major feature of progressive allograft fibrosis, eventually ending with graft loss. Adenosine has been demonstrated to play an important role in process of fibrosis. Our study aimed to investigate the relationship between adenosine and fibrosis in renal allograft acute rejection in rat.Wistar rats and SD rats were selected as experimental animals. Our study designed two groups. In the allograft transplantation group, kidneys of Wistar rats were orthotopically transplanted into SD rat recipients, the same species but not genetically identical, to induce acute rejection. Kidney transplantations of SD rats to SD rats which were genetically identical were served as the control. We established rat models and detected a series of indicators. All data were analyzed statistically. P<0.05 was considered statistically significant.Compared with the control group, levels of adenosine increased significantly in the allograft transplantation group, in which acute rejection was induced (P<0.05. Progressive allograft fibrosis as well as collagen deposition were observed.These findings suggested that level of adenosine was upregulated in acute rejection after kidney allograft transplantation in rat. Acute rejection may promote renal allograft fibrosis via the adenosine signaling pathways.

  19. Cell-matrix interactions in Schistosomal portal fibrosis: a dynamic event

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    Jean-Alexis Grimaud

    1987-01-01

    Full Text Available In recent years, one of the most significant progress in the understanding of liver diseases was the demonstration that liver fibrosis is a dynamic process resulting from a balance between synthesis and degradation of several matrix components, collagen in particular. Thus, fibrosis has been found to be a very early event during liver diseases, be it of toxic, viral or parasitic origin, and to be spontaneously reversible, either partially or totally. In liver fibrosis cell matrix interactions are dependent on the existence of the many factors (sometimes acting in combination which produce the same events at the cellular and molecular levels. These events are: (i the recruitment of fiber-producing cells, (ii their proliferation, (iii the secretion of matrix constituents of the extracellular matrix, and (iv the remodeling and degradation of the newly formed matrix. All these events represent, at least in principle, a target for a therapeutic intervention aimed at influencing the experimentally induced hepatic fibrosis. In this context, hepatosplenic schistosomiasis is of particular interest, being an immune cell-mediated granulomatous disease and a model of liver fibrosis allowing extensive studies in human and animals as well as providing original in vitro models.

  20. Classification of nutritional status in cystic fibrosis.

    Science.gov (United States)

    Lai, HuiChuan J

    2006-11-01

    Nutritional status impacts on the progression of cystic fibrosis. Current guidelines recommend the use of anthropometric indicators to classify nutritional status and identify malnutrition. However, the current nutrition-classification systems are problematic. I summarize these problems and review recent progress in the development of evidence-based anthropometric criteria for classifying nutritional status in cystic fibrosis patients. Percentage of ideal body weight as a malnutrition index is flawed. In children with cystic fibrosis, this index underestimates the severity of underweight in short patients and overestimates it in tall patients. In adults with cystic fibrosis, percentage of ideal body weight based on the Metropolitan Life Insurance reference weights for medium/large frames overestimates the severity of underweight. Body-mass-index percentile for children and body mass index for adults as underweight indices have been proven to be valid. Strong associations between body mass index and lung function are also observed, but cutoff values to maintain a desirable level of lung function can vary. Body mass index should replace the use of percentage of ideal body weight for classifying underweight in cystic fibrosis patients. More research is needed to identify appropriate indicators to classify short stature in children with cystic fibrosis.

  1. Tampão peridural com dextran 40 na profilaxia da cefaléia pós-punção acidental da duramáter em paciente HIV positivo: relato de caso Tampón peridural con dextran 40 en la profilaxia de la cefalea pós-punción accidental de la duramáter en paciente SIDA positivo: relato de caso Epidural patch with dextran 40 to prevent postdural puncture headache in an HIV patient: case report

    OpenAIRE

    Marcos Guilherme Cunha Cruvinel; Paulo Roberto Vieira Barbosa; Vera Coelho Teixeira; Carlos Henrique Viana de Castro

    2002-01-01

    JUSTIFICATIVA E OBJETIVOS: A cefaléia pós-punção de duramáter é uma complicação bem conhecida das anestesias subaracnóideas e peridurais, sendo o tampão sangüíneo considerado o tratamento mais eficaz, até o momento. Este é um procedimento invasivo e sujeito a complicações graves. Seu uso em certos pacientes, como portadores de HIV ou leucemias, é motivo de debate. Várias alternativas têm sido relatadas. O objetivo deste artigo é apresentar um caso do uso do tampão peridural com dextran 40 na ...

  2. Estudo comparativo entre bupivacaína a 0,5% e mistura enantiomérica de bupivacaína (S75-R25 a 0,5% em anestesia peridural Estudio comparativo entre bupivacaína a 0,5% y mezcla enantiomérica de bupivacaína (S75-R25 a 0,5% en anestesia peridural Comparative study between 0.5% bupivacaine and 0.5% enantiomeric mixture of bupivacaine (S75-R25 in epidural anesthesia

    Directory of Open Access Journals (Sweden)

    Rosane Fossatti Gonçalves

    2003-04-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A mistura enantiomérica de bupivacaína (S75-R25 vem sendo empregada pela sua propriedade anestésica com menor toxicidade do que a bupivacaína racêmica. O objetivo deste estudo é comparar a bupivacaína a 0,5% com a mistura enantiomérica de bupivacaína a 0,5% (S75-R25 em anestesia peridural. MÉTODO: Foram incluídos no estudo 44 pacientes divididos em dois grupos (n=22 denominados de Bupivacaína e S75-R25. Os pacientes foram medicados com midazolam por via venosa. A anestesia peridural foi realizada no espaço L3-L4 ou L2-L3, e administrado 16 a 24 ml da solução do anestésico local. O grupo Bupivacaína recebeu bupivacaína a 0,5% com vasoconstritor. O grupo S75-R25 recebeu a mistura enantiomérica de bupivacaína a 0,5% com vasoconstritor. Foram avaliados a temperatura do membro inferior antes e após o bloqueio peridural, o tempo de latência do bloqueio, o tipo de alteração referida pelo paciente, possíveis falhas sensoriais, nível sensorial metamérico e o grau de bloqueio motor. Na sala de recuperação pós-anestésica, foi anotado o tempo de requisição do primeiro analgésico. RESULTADOS: Fizeram parte da avaliação final 41 pacientes. Os grupos foram demograficamente semelhantes. A dose per-operatória de midazolam, o volume de anestésico local por via peridural, o tempo de latência para a instalação do bloqueio, falhas sensoriais a picada da agulha, temperatura do membro inferior nos diferentes tempos, o tipo de sensação parestésica, e o nível anestésico em dermátomos foram semelhantes entre os grupos. O grau de bloqueio motor foi mais intenso para o grupo Bupivacaína, comparado ao grupo S75-R25 (p = 0,0117. O tempo para requisição do primeiro analgésico no período pós-operatório foi superior para o grupo S75-R25, comparado ao grupo Bupivacaína (596 ± 436 minutos versus 463 ± 270 minutos, respectivamente; p = 0,04572. A incidência de efeitos adversos foi semelhante entre

  3. Macrolide antibiotics for cystic fibrosis.

    Science.gov (United States)

    Southern, K W; Barker, P M; Solis, A

    2003-01-01

    The antibiotic treatment of chest infections which characterise cystic fibrosis (CF) has significantly improved prospects for people with CF. The nature of organisms causing these infections has restricted antibiotic choice. Pseudomonas aeruginosa, especially, is resistant to most oral antibiotics. There is evidence from the laboratory and from other disease processes that macrolide antibiotics, whilst not directly active against Pseudomonas aeruginosa, may have indirect actions against this organism. We aimed to test the hypotheses that macrolide antibiotics:(1) improve clinical status compared to placebo or another antibiotic;(2) have no unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.We contacted principal investigators known to work in the field, previous authors and pharmaceutical companies who manufacture macrolide antibiotics for unpublished or follow-up data (December 2002). Date of the most recent search of the Group's register: March 2003. Published or unpublished randomised controlled trials of macrolide antibiotics compared to placebo, another class of antibiotic or another macrolide antibiotic. Studies comparing regimens of the same macrolide antibiotic at different doses will also be included. Two reviewers independently extracted data and assessed study quality. Two groups were contacted for missing data, but these were unavailable for the review. Searches identified eleven studies, two were included in this review (101 participants). One study enrolled adults and the other children (a significant number of whom were not colonised with Pseudomonas aeruginosa). Both studies report small but significant changes in respiratory

  4. Taurine attenuates radiation-induced lung fibrosis in C57/Bl6 fibrosis prone mice.

    LENUS (Irish Health Repository)

    Robb, W B

    2010-03-01

    The amino acid taurine has an established role in attenuating lung fibrosis secondary to bleomycin-induced injury. This study evaluates taurine\\'s effect on TGF-beta1 expression and the development of lung fibrosis after single-dose thoracic radiotherapy.

  5. Tampão peridural com dextran 40 na profilaxia da cefaléia pós-punção acidental da duramáter em paciente HIV positivo: relato de caso Tampón peridural con dextran 40 en la profilaxia de la cefalea pós-punción accidental de la duramáter en paciente SIDA positivo: relato de caso Epidural patch with dextran 40 to prevent postdural puncture headache in an HIV patient: case report

    Directory of Open Access Journals (Sweden)

    Marcos Guilherme Cunha Cruvinel

    2002-11-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A cefaléia pós-punção de duramáter é uma complicação bem conhecida das anestesias subaracnóideas e peridurais, sendo o tampão sangüíneo considerado o tratamento mais eficaz, até o momento. Este é um procedimento invasivo e sujeito a complicações graves. Seu uso em certos pacientes, como portadores de HIV ou leucemias, é motivo de debate. Várias alternativas têm sido relatadas. O objetivo deste artigo é apresentar um caso do uso do tampão peridural com dextran 40 na profilaxia da cefaléia pós-punção de duramáter em paciente portador do vírus da imunodeficiência humana (HIV, com história de cefaléia em anestesia subaracnóidea anterior. RELATO DE CASO: Paciente masculino, 31 anos, 70 kg, estado físico ASA II, portador de HIV, para tratamento de condilomatose anal recidivada, com relato de cefaléia intensa e limitante durante duas semanas após anestesia subaracnóidea (agulha Quincke 25G. Durante tentativa de anestesia peridural com agulha de Tuohy 18G em L3-L4, houve perfuração acidental da duramáter. Foram injetados, por duas vezes, 20 ml de dextran 40 a 10% por cateter peridural; a primeira, 150 minutos após a administração dos anestésicos e a segunda na manhã seguinte à cirurgia. O paciente evoluiu assintomático e recebeu alta no dia seguinte à sua internação. CONCLUSÕES: O uso do tampão com soluções colóides como o dextran 40 não está bem estabelecido, porém existem alguns relatos do seu uso com sucesso e entendemos que seu potencial deva ser melhor explorado.JUSTIFICATIVA Y OBJETIVOS: La cefalea pós-punción de duramáter es una complicación bien conocida de las anestesias subaracnóideas y peridurales, siendo el tampón sanguíneo considerado el tratamiento más eficaz hasta el momento. Este es un procedimiento invasivo y sujeto a complicaciones graves. Su uso en ciertos pacientes, como portadores de SIDA o leucemias, es motivo de debate. Varias alternativas

  6. Male fertility in cystic fibrosis.

    LENUS (Irish Health Repository)

    Chotirmall, S H

    2011-04-05

    Infertility rates among males with cystic fibrosis (CF) approximate 97%. No information is currently available within Ireland determining an understanding of fertility issues and the best methods of information provision to this specialized group. This study aimed to determine understanding and preferred approaches to information provision on fertility issues to Irish CF males. A Descriptive Study utilizing prospective coded questionnaires was mailed to a male CF cohort (n=50). Sections included demographics, fertility knowledge & investigation. Response rate was 16\\/50 (32%). All were aware that CF affected their fertility. More than two-thirds (n=11) were able to provide explanations whilst only one-third (n=5) provided the correct explanation. Significant numbers stated thoughts of marriage and a future family. Half have discussed fertility with a healthcare professional (HCP). Mean age of discussion was 21.9 years. One third preferred an earlier discussion. The commonest first source for information was written material which was also the preferred source. Three-quarters requested further information preferring again, written material. Significant gaps in sex education of Irish CF males exist. Discussion should be initiated by HCPs and centre-directed written material devised to address deficiencies.

  7. Cystic fibrosis: a clinical view.

    Science.gov (United States)

    Castellani, Carlo; Assael, Baroukh M

    2017-01-01

    Cystic fibrosis (CF), a monogenic disease caused by mutations in the CFTR gene on chromosome 7, is complex and greatly variable in clinical expression. Airways, pancreas, male genital system, intestine, liver, bone, and kidney are involved. The lack of CFTR or its impaired function causes fat malabsorption and chronic pulmonary infections leading to bronchiectasis and progressive lung damage. Previously considered lethal in infancy and childhood, CF has now attained median survivals of 50 years of age, mainly thanks to the early diagnosis through neonatal screening, recognition of mild forms, and an aggressive therapeutic attitude. Classical treatment includes pancreatic enzyme replacement, respiratory physiotherapy, mucolitics, and aggressive antibiotic therapy. A significant proportion of patients with severe symptoms still requires lung or, less frequently, liver transplantation. The great number of mutations and their diverse effects on the CFTR protein account only partially for CF clinical variability, and modifier genes have a role in modulating the clinical expression of the disease. Despite the increasing understanding of CFTR functioning, several aspects of CF need still to be clarified, e.g., the worse outcome in females, the risk of malignancies, the pathophysiology, and best treatment of comorbidities, such as CF-related diabetes or CF-related bone disorder. Research is focusing on new drugs restoring CFTR function, some already available and with good clinical impact, others showing promising preliminary results that need to be confirmed in phase III clinical trials.

  8. Infection control in cystic fibrosis.

    Science.gov (United States)

    Saiman, Lisa; Siegel, Jane

    2004-01-01

    Over the past 20 years there has been a greater interest in infection control in cystic fibrosis (CF) as patient-to-patient transmission of pathogens has been increasingly demonstrated in this unique patient population. The CF Foundation sponsored a consensus conference to craft recommendations for infection control practices for CF care providers. This review provides a summary of the literature addressing infection control in CF. Burkholderia cepacia complex, Pseudomonas aeruginosa, and Staphylococcus aureus have all been shown to spread between patients with CF. Standard precautions, transmission-based precautions including contact and droplet precautions, appropriate hand hygiene for health care workers, patients, and their families, and care of respiratory tract equipment to prevent the transmission of infectious agents serve as the foundations of infection control and prevent the acquisition of potential pathogens by patients with CF. The respiratory secretions of all CF patients potentially harbor clinically and epidemiologically important microorganisms, even if they have not yet been detected in cultures from the respiratory tract. CF patients should be educated to contain their secretions and maintain a distance of >3 ft from other CF patients to avoid the transmission of potential pathogens, even if culture results are unavailable or negative. To prevent the acquisition of pathogens from respiratory therapy equipment used in health care settings as well as in the home, such equipment should be cleaned and disinfected. It will be critical to measure the dissemination, implementation, and potential impact of these guidelines to monitor changes in practice and reduction in infections.

  9. Respiratory Conditions Update: Cystic Fibrosis.

    Science.gov (United States)

    Pritchard, Lyle L

    2016-09-01

    Cystic fibrosis (CF) is an autosomal recessive genetic disease that occurs in approximately 1 in 2,500 white live births. It is less common in nonwhite individuals. A dysfunctional epithelial chloride channel leads to excessively thick mucus affecting multiple organ systems. Common issues include mucous plugging of the airway, lung inflammation, chronic pulmonary infections, intestinal malabsorption, and malnutrition. Universal screening of newborns for CF is recommended in many countries. CF can be diagnosed based on clinical evidence of disease along with genetic testing or other laboratory evidence of chloride channel dysfunction. Pulmonary system dysfunction causes the most morbidity and mortality. Pulmonary function testing is the primary modality used to monitor CF progression. Therapies include chest physiotherapy, mucolytics, antibiotics, anti-inflammatory drugs, targeted therapies, and vaccines. Dysfunction of the exocrine pancreas and gastrointestinal tract leads to malabsorption, malnutrition, and intestinal obstruction. Nutrition should be optimized with adequate calories, pancreatic enzymes, and appropriate dietary supplements. Complications, including acute pulmonary exacerbations, gastrointestinal conditions, chronic rhinosinusitis, CF-related diabetes, osteoporosis, infertility, and psychosocial issues, must be managed. At the appropriate time, lung transplantation and end-of-life issues must be addressed. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  10. Liver Disease in Cystic Fibrosis: an Update

    Science.gov (United States)

    Parisi, Giuseppe Fabio; Di Dio, Giovanna; Franzonello, Chiara; Gennaro, Alessia; Rotolo, Novella; Lionetti, Elena; Leonardi, Salvatore

    2013-01-01

    Context Cystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emergedespecially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF. Evidence Acquisition A literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library. Results CF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause ofmortalityin CF (the third after pulmonary disease and transplant complications), only about the 33%ofCF patients presents clinically significant hepatobiliary disease. Conclusions Liver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed atdelaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of

  11. Liver disease in cystic fibrosis: an update.

    Science.gov (United States)

    Parisi, Giuseppe Fabio; Di Dio, Giovanna; Franzonello, Chiara; Gennaro, Alessia; Rotolo, Novella; Lionetti, Elena; Leonardi, Salvatore

    2013-08-14

    Cystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emerged especially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF. A literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library. CF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause of mortality in CF (the third after pulmonary disease and transplant complications), only about the 33%of CF patients presents clinically significant hepatobiliary disease. Liver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed at delaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of fibrosis prevention and to avoid its

  12. Effect of lung fibrosis on glycogen content in different extrapulmonary tissues.

    Science.gov (United States)

    Borges, Elizabeth Lage; de Barros Pinheiro, Marina; Prata, Luana Oliveira; Sales, Wesley Araújo; Silva, Yuri Augusto Junqueira Belém; Caliari, Marcelo Vidigal; Rodrigues-Machado, Maria Glória; da Glória Rodrigues-Machado, Maria

    2014-02-01

    Patients with pulmonary fibrosis often exhibit reduced lung function and diminished health-related quality of life. Studies have shown that paraquat-induced, extrapulmonary, acute lung injury affects the metabolic profile of glycogen content in different tissues. The purpose of the present study was to investigate whether the process of pulmonary fibrosis induced by continuous exposure to the toxic herbicide paraquat or by a local insult from bleomycin affects the glycogen content in tissues. In the paraquat experiment, Wistar rats (n = 5 per group) received either saline (controls) or an intraperitoneal injection of a paraquat solution (7.0 mg/kg; experimental group) once a week for 4 weeks. In the bleomycin experiment, Balb/c mice (n = 5 per group) received either saline (controls) or 6.25 U/kg of bleomycin through intratracheal instillation in single dose (experimental group). Glycogen content in different tissues (mg/g tissue) was measured using the anthrone reagent. The lungs submitted to histopathological and quantitative analyses of fibrosis. Paraquat-induced fibrosis led to lower glycogen content in the gastrocnemius muscle (2.7 ± 0.1 vs. 3.4 ± 0.1; 79 %) compared with the controls, whereas no changes in glycogen content were found in the diaphragm or heart. Bleomycin-induced fibrosis led to lower glycogen content in the diaphragm (0.43 ± 0.02 vs. 0.79 ± 0.09, 54 %), gastrocnemius muscle (0.62 ± 0.11 vs. 1.18 ± 0.06, 52 %), and heart (0.68 ± 0.11 vs. 1.39 ± 0.1, 49 %) compared with the controls (p < 0.05). Moreover, the area of fibrous connective tissue (μm(2)) in the lungs was significantly increased in paraquat-induced fibrosis (3,463 ± 377 vs. 565 ± 89) and bleomycin-induced fibrosis (3,707 ± 433.9 vs. 179 ± 51.28) compared with the controls. The findings suggest that the effects of fibrogenesis in the lungs are not limited to local alterations but also lead to a reduction in glycogen content in the heart

  13. Is neutrophil elastase the missing link between emphysema and fibrosis? Evidence from two mouse models

    Directory of Open Access Journals (Sweden)

    Martorana Piero A

    2005-07-01

    Full Text Available Abstract Background The separation of emphysema from fibrosis is not as clear-cut as it was thought in early studies. These two pathologies may be present at the same time in human lungs and in mice either instilled with elastolytic enzymes or bleomycin or exposed to cigarette-smoke. According to a current view, emphysema originates from a protease/antiprotease imbalance, and a role for antiproteases has also been suggested in the modulation of the fibrotic process. In this study we investigate in experimental animal models of emphysema and fibrosis whether neutrophil elastase may constitute a pathogenic link between these two pathologies. Methods This study was done in two animal models in which emphysema and fibrosis were induced either by bleomycin (BLM or by chronic exposure to cigarette-smoke. In order to assess the protease-dependence of the BLM-induced lesion, a group mice was treated with 4-(2-aminoethyl-benzenesulfonyl fluoride hydrochloride, a serine proteinase inhibitor active toward neutrophil elastase. Lungs from each experimental group were used for the immunohistochemical assessment of transforming growth factor-β (TGF-β and transforming growth factor-α (TGF-α and for determination of the mean linear intercept as well as the percent volume densities of fibrosis and of emphysematous changes. Additionally, the lungs were also assessed for desmosine content and for the determination of elastase levels in the pulmonary interstitium by means of immunoelectron microscopy. Results We demonstrate that in BLM-treated mice (i the development of elastolytic emphysema precedes that of fibrosis; (ii significant amount of elastase in alveolar interstitium is associated with an increased expression of TGF-β and TGF-α; and finally, (iii emphysematous and fibrotic lesions can be significantly attenuated by using a protease inhibitor active against neutrophil elastase. Also, in a strain of mice that develop both emphysema and fibrosis after

  14. Pathogenic aspects and therapeutic avenues of intestinal fibrosis in Crohn's disease.

    Science.gov (United States)

    Zorzi, Francesca; Calabrese, Emma; Monteleone, Giovanni

    2015-12-01

    In Crohn's disease, one of the two major forms of inflammatory bowel diseases in human beings, persistent and chronic inflammation promotes fibrotic processes thereby facilitating formation of strictures, the most common indication for surgical intervention in this disorder. The pathogenesis of Crohn's disease-associated fibrosis is not fully understood, but variants of genes involved in the recognition of microbial components/products [e.g. CARD15 (caspase-activating recruitment domain 15) and ATG16L1 (autophagy-related 16-like 1)] are associated with this phenotype, and experimental evidence suggests that intestinal fibrosis results from an altered balance between deposition of ECM (extracellular matrix) and degradation of ECM by proteases. Studies have also contributed to identify the main phenotypic and functional alterations of cells involved in the fibrogenic process, as well as molecules that stimulate such cells to produce elevated amounts of collagen and other ECM-related proteins. In the present review, we assess the current knowledge about cellular and molecular mediators of intestinal fibrosis and describe results of recent studies aimed at testing the preventive/therapeutic effect of compounds in experimental models of intestinal fibrosis. © 2015 Authors; published by Portland Press Limited.

  15. Congenital fibrosis of the extraocular muscles.

    Science.gov (United States)

    Harley, R D; Rodrigues, M M; Crawford, J S

    1978-01-01

    Congential fibrosis of the extraocular muscles is characterized by the replacement of normal contractile muscle tissue by fibrous tissue or fibrous bands in varying degrees. The clinical entities which result from the fibrous replacement can be classified under the following headings: general fibrosis syndrome, congenital fibrosis of the inferior rectus muscle with blepharoptosis, strabismus fixus, vertical retraction syndrome and congential unilateral fibrosis, enophthalmos and blepharoptosis. Genetic factors may or may not be apparent. One pedigree with general fibrosis syndrome was traced through five generations. Light and electron microscopy demonstrated replacement of normal muscle by collagen and dense fibrous tissue with occasional areas of degenerated skeletal muscle. The surgical mangement attempts to achieve some functional readjustment of the ocular and lid position as well as the abnormal head posture. The surgical results were considered satisfactory when compared with the original position of the eyes and the backward head tilt. Images FIGURE 1 A FIGURE 1 B FIGURE 1 C FIGURE 2 A FIGURE 2 B FIGURE 2 C FIGURE 3 A FIGURE 3 B FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 A FIGURE 7 B FIGURE 7 C FIGURE 8 A FIGURE 8 B FIGURE 9 A FIGURE 9 B FIGURE 9 C FIGURE 9 D PMID:754372

  16. Cellular and molecular mechanisms of intestinal fibrosis.

    Science.gov (United States)

    Speca, Silvia; Giusti, Ilaria; Rieder, Florian; Latella, Giovanni

    2012-07-28

    Fibrosis is a chronic and progressive process characterized by an excessive accumulation of extracellular matrix (ECM) leading to stiffening and/or scarring of the involved tissue. Intestinal fibrosis may develop in several different enteropathies, including inflammatory bowel disease. It develops through complex cell, extracellular matrix, cytokine and growth factor interactions. Distinct cell types are involved in intestinal fibrosis, such as resident mesenchymal cells (fibroblasts, myofibroblasts and smooth muscle cells) but also ECM-producing cells derived from epithelial and endothelial cells (through a process termed epithelial- and endothelial-mesenchymal transition), stellate cells, pericytes, local or bone marrow-derived stem cells. The most important soluble factors that regulate the activation of these cells include cytokines, chemokines, growth factors, components of the renin-angiotensin system, angiogenic factors, peroxisome proliferator-activated receptors, mammalian target of rapamycin, and products of oxidative stress. It soon becomes clear that although inflammation is responsible for triggering the onset of the fibrotic process, it only plays a minor role in the progression of this condition, as fibrosis may advance in a self-perpetuating fashion. Definition of the cellular and molecular mechanisms involved in intestinal fibrosis may provide the key to developing new therapeutic approaches.

  17. Chronic hepatitis C and liver fibrosis.

    Science.gov (United States)

    Sebastiani, Giada; Gkouvatsos, Konstantinos; Pantopoulos, Kostas

    2014-08-28

    Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the next decades, posing a major health care challenge. This review provides a brief update on HCV epidemiology, summarizes basic mechanistic concepts of HCV-dependent liver fibrogenesis, and discusses methods for assessment of liver fibrosis that are routinely used in clinical practice. Liver biopsy was until recently considered as the gold standard to diagnose and stage liver fibrosis. However, its invasiveness and drawbacks led to the development of non-invasive methods, which include serum biomarkers, transient elastography and combination algorithms. Clinical studies with CHC patients demonstrated that non-invasive methods are in most cases accurate for diagnosis and for monitoring liver disease complications. Moreover, they have a high prognostic value and are cost-effective. Non-invasive methods for assessment of liver fibrosis are gradually being incorporated into new guidelines and are becoming standard of care, which significantly reduces the need for liver biopsy.

  18. The Role of Catalase in Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Takigawa Tomoko

    2010-12-01

    Full Text Available Abstract Background Catalase is preferentially expressed in bronchiolar and alveolar epithelial cells, and acts as an endogenous antioxidant enzyme in normal lungs. We thus postulated epithelial damage would be associated with a functional deficiency of catalase during the development of lung fibrosis. Methods The present study evaluates the expression of catalase mRNA and protein in human interstitial pneumonias and in mouse bleomycin-induced lung injury. We examined the degree of bleomycin-induced inflammation and fibrosis in the mice with lowered catalase activity. Results In humans, catalase was decreased at the levels of activity, protein content and mRNA expression in fibrotic lungs (n = 12 compared to control lungs (n = 10. Immunohistochemistry revealed a decrease in catalase in bronchiolar epithelium and abnormal re-epithelialization in fibrotic areas. In C57BL/6J mice, catalase activity was suppressed along with downregulation of catalase mRNA in whole lung homogenates after bleomycin administration. In acatalasemic mice, neutrophilic inflammation was prolonged until 14 days, and there was a higher degree of lung fibrosis in association with a higher level of transforming growth factor-β expression and total collagen content following bleomycin treatment compared to wild-type mice. Conclusions Taken together, these findings demonstrate diminished catalase expression and activity in human pulmonary fibrosis and suggest the protective role of catalase against bleomycin-induced inflammation and subsequent fibrosis.

  19. Acute exacerbation of airspace enlargement with fibrosis

    Directory of Open Access Journals (Sweden)

    Tomoyuki Kakugawa

    2014-01-01

    Full Text Available In 2008, Kawabata et al. described a lesion which they termed “airspace enlargement with fibrosis” that could be included on the spectrum of smoking-related interstitial lung diseases. This group also reported that patients with airspace enlargement with fibrosis but without coexisting interstitial pneumonia of another type had no acute exacerbations and favorable prognoses on clinical follow-up. Here we describe the first case, to our knowledge, of acute exacerbation of airspace enlargement with fibrosis without coexisting interstitial pneumonia of another type. An 82-year-old man was referred to our department for worsening dyspnea and new alveolar opacities on chest radiograph following left pulmonary segmentectomy (S6 for cancer. A diagnosis of acute exacerbation of airspace enlargement with fibrosis without coexisting interstitial pneumonia of other types was made, based on pathological evidence of airspace enlargement with fibrosis and organizing diffuse alveolar damage. Treatment with high-dose methylprednisolone followed by tapered oral prednisolone resulted in gradual improvement of the clinical condition and chest radiographic findings. Clinicians should be aware that patients with airspace enlargement with fibrosis may experience acute exacerbation.

  20. Retroperitoneal fibrosis: case report and literature review

    Directory of Open Access Journals (Sweden)

    José Francisco Camacho

    2013-09-01

    Full Text Available Introduction. The first description of extrinsic uretheral obstruction by retroperitoneal fibrosis occurred in 1905. In little more than a century, about 800 cases of this disease have been reported. Case description. We report the case of a female 55 year-old patient who presents with diffuse abdominal pain of long duration, nausea, vomiting, fever of 38°C and hypertension of 160/100 mmHg. A CT scan is performed that shows a retroperitoneal mass that obstructs the urethers. Exploratory laparotomy was performed, urethers were released and biopsy was taken. Pathology analysis showed the presence of retroperitoneal fibrosis, a rare pathological entity whose diagnosis requires a high index of suspicion based on clinical, imaging and laboratory workup. Literature review. There are no clear definitions of the variety of disorders that are included in the spectrum of retroperitoneal fibrosis, due to the rarity of this condition. Consequently, we lack diagnostic criteria and a consistent classification of the different forms that it may adopt. However, when there is suspicion of retroperitoneal fibrosis, the first step is to establish whether it is idiopathic or secondary, as there will be treatment implications. Conclusion. Retroperitoneal fibrosis should be considered in the differential diagnosis whenever diffuse abdominal pain is associated with uretheral or great vessels compression.

  1. Results of the 4th scientific workshop of the ECCO (I): pathophysiology of intestinal fibrosis in IBD.

    Science.gov (United States)

    Latella, Giovanni; Rogler, Gerhard; Bamias, Giorgos; Breynaert, Christine; Florholmen, Jon; Pellino, Gianluca; Reif, Shimon; Speca, Silvia; Lawrance, Ian C

    2014-10-01

    The fourth scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on the relevance of intestinal fibrosis in the disease course of inflammatory bowel disease (IBD). The objective was to better understand the pathophysiological mechanisms of intestinal fibrosis, to identify useful markers and imaging modalities of fibrosis in order to assess its presence and progression, and, finally, to point out possible approaches for the prevention and the treatment of fibrosis. The results of this workshop are presented in three separate manuscripts. This first section describes the most important mechanisms that contribute to the initiation and progression of intestinal fibrosis in IBD including the cellular and molecular mediators, the extracellular matrix molecules and matrix metalloproteinases/tissue inhibitors of metalloproteinases-system, the microbiota products, the role of fat, genetic and epigenetic factors, as well as the currently available experimental models. Furthermore, it identifies unanswered questions in the field of intestinal fibrosis and provides a framework for future research. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  2. New therapeutic target for the non-electrophysiological signaling in atrial fibrosis and fibrillation such as inflammation

    Directory of Open Access Journals (Sweden)

    Naohiko Takahashi

    2012-06-01

    Full Text Available We have experimentally established appropriate models of atrial fibrillation (AF with atrial interstitial fibrosis. Two approaches were adopted. Firstly, left atrial fibrosis was induced by continuous infusion of angiotensin II (AII. In an electrophysiological study using isolated perfused heart, AF was easily induced following AII treatment. Repeated whole-body hyperthermia led to the induction of heat-shock protein 72, which resulted in attenuation of AII-induced left atrial fibrosis and suppression of AF inducibility. Secondly, atrial fibrosis was induced by pressure overload by abdominal aortic constriction (AAC. AAC enhanced left atrial expression of monocyte chemoattractant protein-1 and activity of matrix metalloproteinase-9. Treatment with pioglitazone, a peroxisome proliferator-activated receptor-γ agonist, resulted in attenuation of pressure overload-induced left atrial fibrosis and suppression of AF inducibility. In the same AAC model, the effects of candesartan on gap junction remodeling were investigated. Connexin 43 (Cx43 of the left atria was firmly located in the intercalated disks in control rats. A progressive redistribution of Cx43 from the intercalated disk to the lateral surface (lateralization was observed in AAC rats. Candesartan prevented left Cx43 lateralization. Thus, heat-shock proteins, pioglitazone, and candesartan could be novel therapeutic approaches to prevent atrial fibrosis and AF.

  3. Genetics Home Reference: congenital fibrosis of the extraocular muscles

    Science.gov (United States)

    ... the extraocular muscles congenital fibrosis of the extraocular muscles Printable PDF Open All Close All Enable Javascript ... collapse boxes. Description Congenital fibrosis of the extraocular muscles is a disorder that affects the muscles that ...

  4. Cystic Fibrosis-Related Diabetes (CFRD): Daily Management

    Science.gov (United States)

    Cystic Fibrosis-Related Diabetes (CFRD): Daily Management September 20, 2011 This Web cast is supported by an unrestricted ... Moran, MD Professor, Pediatric Endocrinology University of Minnesota Cystic Fibrosis-Related Diabetes (CFRD): Daily Management September 20, 2011 ...

  5. Gastroenterological endpoints in drug trials for cystic fibrosis

    NARCIS (Netherlands)

    Bodewes, Frank A. J. A.; Verkade, Henkjan J.; Wilschanski, Micheal

    2016-01-01

    The phenotype of cystic fibrosis includes a wide variety of clinical and biochemical gastrointestinal presentations. These gastrointestinal characteristics of the disease have come under renewed interest as potential outcome measures and clinical endpoints for therapeutic trials in cystic fibrosis.

  6. Ketamine induced renal fibrosis in a ketamine addition rat model

    Directory of Open Access Journals (Sweden)

    Mei-Yu Jang

    2017-09-01

    Conclusion: Ketamine treatment not only induced cystitis-like syndrome, but also renal fibrosis. These renal interstitial fibrosis changes may be induced by the TGF-β pathway. These preliminary results can provide valuable information from a clinical perspective.

  7. CXCR4+ granulocytes reflect fungal cystic fibrosis lung disease

    National Research Council Canada - National Science Library

    Carevic, Melanie; Singh, Anurag; Rieber, Nikolaus; Eickmeier, Olaf; Griese, Matthias; Hector, Andreas; Hartl, Dominik

    2015-01-01

    ... understood.We characterised granulocytes in airway fluids and peripheral blood from cystic fibrosis patients with and without fungal colonisation, non-cystic fibrosis disease controls and healthy control...

  8. CXCR4+ granulocytes reflect fungal cystic fibrosis lung disease.

    Science.gov (United States)

    Carevic, Melanie; Singh, Anurag; Rieber, Nikolaus; Eickmeier, Olaf; Griese, Matthias; Hector, Andreas; Hartl, Dominik

    2015-08-01

    Cystic fibrosis airways are frequently colonised with fungi. However, the interaction of these fungi with immune cells and the clinical relevance in cystic fibrosis lung disease are incompletely understood.We characterised granulocytes in airway fluids and peripheral blood from cystic fibrosis patients with and without fungal colonisation, non-cystic fibrosis disease controls and healthy control subjects cross-sectionally and longitudinally and correlated these findings with lung function parameters.Cystic fibrosis patients with chronic fungal colonisation by Aspergillus fumigatus were characterised by an accumulation of a distinct granulocyte subset, expressing the HIV coreceptor CXCR4. Percentages of airway CXCR4(+) granulocytes correlated with lung disease severity in patients with cystic fibrosis.These studies demonstrate that chronic fungal colonisation with A. fumigatus in cystic fibrosis patients is associated with CXCR4(+) airway granulocytes, which may serve as a potential biomarker and therapeutic target in fungal cystic fibrosis lung disease. Copyright ©ERS 2015.

  9. Ablation of biglycan attenuates cardiac hypertrophy and fibrosis after left ventricular pressure overload.

    Science.gov (United States)

    Beetz, Nadine; Rommel, Carolin; Schnick, Tilman; Neumann, Elena; Lother, Achim; Monroy-Ordonez, Elsa Beatriz; Zeeb, Martin; Preissl, Sebastian; Gilsbach, Ralf; Melchior-Becker, Ariane; Rylski, Bartosz; Stoll, Monika; Schaefer, Liliana; Beyersdorf, Friedhelm; Stiller, Brigitte; Hein, Lutz

    2016-12-01

    Biglycan, a small leucine-rich proteoglycan, has been shown to play an important role in stabilizing fibrotic scars after experimental myocardial infarction. However, the role of biglycan in the development and regression of cardiomyocyte hypertrophy and fibrosis during cardiac pressure overload and unloading remains elusive. Thus, the aim of the present study was to assess the effect of biglycan on cardiac remodeling in a mouse model of left ventricular pressure overload and unloading. Left ventricular pressure overload induced by transverse aortic constriction (TAC) in mice resulted in left ventricular dysfunction, fibrosis and increased biglycan expression. Fluorescence- and magnetic-assisted sorting of cardiac cell types revealed upregulation of biglycan in the fibroblast population, but not in cardiomyocytes, endothelial cells or leukocytes after TAC. Removal of the aortic constriction (rTAC) after short-term pressure overload (3weeks) improved cardiac contractility and reversed ventricular hypertrophy but not fibrosis in wild-type (WT) mice. Biglycan ablation (KO) enhanced functional recovery but did not resolve cardiac fibrosis. After long-term TAC for 9weeks, ablation of biglycan attenuated the development of cardiac hypertrophy and fibrosis. In vitro, biglycan induced hypertrophy of neonatal rat cardiomyocytes and led to activation of a hypertrophic gene program. Putative downstream mediators of biglycan signaling include Rcan1, Abra and Tnfrsf12a. These genes were concordantly induced by TAC in WT but not in biglycan KO mice. Left ventricular pressure overload induces biglycan expression in cardiac fibroblasts. Ablation of biglycan improves cardiac function and attenuates left ventricular hypertrophy and fibrosis after long-term pressure overload. In vitro biglycan induces hypertrophy of cardiomyocytes, suggesting that biglycan may act as a signaling molecule between cell types to modulate cardiac remodeling. Copyright © 2016 Elsevier Ltd. All rights

  10. Profibrotic potential of Prominin-1+ epithelial progenitor cells in pulmonary fibrosis

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    Lüscher Thomas F

    2011-09-01

    Full Text Available Abstract Background In idiopathic pulmonary fibrosis loss of alveolar epithelium induces inflammation of the pulmonary tissue followed by accumulation of pathogenic myofibroblasts leading eventually to respiratory failures. In animal models inflammatory and resident cells have been demonstrated to contribute to pulmonary fibrosis. Regenerative potential of pulmonary and extra-pulmonary stem and progenitor cells raised the hope for successful treatment option against pulmonary fibrosis. Herein, we addressed the contribution of lung microenvironment and prominin-1+ bone marrow-derived epithelial progenitor cells in the mouse model of bleomycin-induced experimental pulmonary fibrosis. Methods Prominin-1+ bone marrow-derived epithelial progenitors were expanded from adult mouse lungs and differentiated in vitro by cytokines and growth factors. Pulmonary fibrosis was induced in C57Bl/6 mice by intratracheal instillation of bleomycin. Prominin-1+ progenitors were administered intratracheally at different time points after bleomycin challenge. Green fluorescence protein-expressing cells were used for cell tracking. Cell phenotypes were characterized by immunohistochemistry, flow cytometry and quantitative reverse transcription-polymerase chain reaction. Results Prominin-1+ cells expanded from healthy lung represent common progenitors of alveolar type II epithelial cells, myofibroblasts, and macrophages. Administration of prominin-1+ cells 2 hours after bleomycin instillation protects from pulmonary fibrosis, and some of progenitors differentiate into alveolar type II epithelial cells. In contrast, prominin-1+ cells administered at day 7 or 14 lose their protective effects and differentiate into myofibroblasts and macrophages. Bleomycin challenge enhances accumulation of bone marrow-derived prominin-1+ cells within inflamed lung. In contrast to prominin-1+ cells from healthy lung, prominin-1+ precursors isolated from inflamed organ lack regenerative

  11. Genetic and epigenetic regulation of intestinal fibrosis.

    Science.gov (United States)

    Li, Chao; Kuemmerle, John F

    2016-08-01

    Crohn's disease affects those individuals with polygenic risk factors. The identified risk loci indicate that the genetic architecture of Crohn's disease involves both innate and adaptive immunity and the response to the intestinal environment including the microbiome. Genetic risk alone, however, predicts only 25% of disease, indicating that other factors, including the intestinal environment, can shape the epigenome and also confer heritable risk to patients. Patients with Crohn's disease can have purely inflammatory disease, penetrating disease or fibrostenosis. Analysis of the genetic risk combined with epigenetic marks of Crohn's disease and other disease associated with organ fibrosis reveals common events are affecting the genes and pathways key to development of fibrosis. This review will focus on what is known about the mechanisms by which genetic and epigenetic risk factors determine development of fibrosis in Crohn's disease and contrast that with other fibrotic conditions.

  12. Fibrocytes in pulmonary fibrosis: a brief synopsis

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    Shyam Maharaj

    2013-12-01

    Full Text Available Fibrocytes are bone marrow-derived, circulating mesenchymal progenitor cells that play a role in several fibrotic disorders, including lung fibrosis. They are attracted to injured tissue by various chemokines. It is likely that fibrocytes play a detrimental role in tissue homeostasis and promote fibrosis, although this paradigm needs further confirmation. This would make fibrocytes a possible novel treatment target for fibrotic disorders. Fibrocytes also have some potential as a biomarker for idiopathic pulmonary fibrosis (IPF and other diseases, but the promising preliminary data from single centre studies still require independent validation. Despite several, as yet, unresolved issues, it has become clear that fibrocytes are more than an incidental finding in lung injury and repair, and may hold great promise for the future of IPF management.

  13. Inhibition of the Unfolded Protein Response Mechanism Prevents Cardiac Fibrosis

    OpenAIRE

    Jody Groenendyk; Dukgyu Lee; Joanna Jung; Dyck, Jason R B; Lopaschuk, Gary D.; Agellon, Luis B.; Marek Michalak

    2016-01-01

    Background Cardiac fibrosis attributed to excessive deposition of extracellular matrix proteins is a major cause of heart failure and death. Cardiac fibrosis is extremely difficult and challenging to treat in a clinical setting due to lack of understanding of molecular mechanisms leading to cardiac fibrosis and effective anti-fibrotic therapies. The objective in this study was to examine whether unfolded protein response (UPR) pathway mediates cardiac fibrosis and whether a pharmacological in...

  14. Imaging of intestinal fibrosis: current challenges and future methods

    OpenAIRE

    STIDHAM, RYAN W.; Higgins, Peter DR

    2016-01-01

    Crohn’s disease (CD) activity assessments are dominated by inflammatory changes without discrete measurement of the coexisting fibrotic contribution to total bowel damage. Intestinal fibrosis impacts the development of severe structural complications and the overall natural history of CD. Measuring intestinal fibrosis is challenging and existing methods of disease assessment are unable to reliably distinguish fibrosis from inflammation. Both the immediate clinical need to measure fibrosis for...

  15. Noninvasive monitoring of pulmonary fibrosis by targeting matrix metalloproteinases (MMPs).

    Science.gov (United States)

    Cai, Yan; Zhu, Lei; Zhang, Fan; Niu, Gang; Lee, Seulki; Kimura, Shioko; Chen, Xiaoyuan

    2013-06-03

    While idiopathic pulmonary fibrosis (PF) is a devastating lung disease, the management of PF including effective monitoring of disease progression remains a challenge. Herein, we introduce a novel, fast, and ultrasensitive metalloproteinase (MMP) activatable optical probe, named MMP-P12, to noninvasively monitor PF progression and response to PF treatment. A bleomycin (BLM)-induced mouse PF model was subjected noninvasively to optical imaging at various time points after BLM treatment. The mouse PF model developed fibrosis during 21 days of experimental period, and the progression of PF was well correlated with the stepwise increase of MMP-2 expression as examined by quantitative RT-PCR and Western blot analysis on the 7-, 14-, and 21-day post-BLM administration. On these days, MMP-activated fluorescence images were acquired in vivo and ex vivo. Signal quantification showed time-dependent lung-specific incremental increases in fluorescence signals. As a treatment for PF, secretoglobin 3A2 was daily administered intravenously for five days starting on day seven of BLM administration, which resulted in reduced MMP-2 activity and reduction of PF as previously demonstrated. Importantly, the fluorescence signal that reflected MMP activity also decreased in intensity. In conclusion, MMPs may play an important role in PF development and the MMP-P12 probe could be a promising tool for PF detection, even at an early stage of the disease as well as an indicator of therapy response.

  16. Non-Invasive markers for hepatic fibrosis

    Directory of Open Access Journals (Sweden)

    Lal Priyanka

    2011-08-01

    Full Text Available Abstract With great advancements in the therapeutic modalities used for the treatment of chronic liver diseases, the accurate assessment of liver fibrosis is a vital need for successful individualized management of disease activity in patients. The lack of accurate, reproducible and easily applied methods for fibrosis assessment has been the major limitation in both the clinical management and for research in liver diseases. However, the problem of the development of biomarkers capable of non-invasive staging of fibrosis in the liver is difficult due to the fact that the process of fibrogenesis is a component of the normal healing response to injury, invasion by pathogens, and many other etiologic factors. Current non-invasive methods range from serum biomarker assays to advanced imaging techniques such as transient elastography and magnetic resonance imaging (MRI. Among non-invasive methods that gain strongest clinical foothold are FibroScan elastometry and serum-based APRI and FibroTest. There are many other tests that are not yet widely validated, but are none the less, promising. The rate of adoption of non-invasive diagnostic tests for liver fibrosis differs from country to country, but remains limited. At the present time, use of non-invasive procedures could be recommended as pre-screening that may allow physicians to narrow down the patients' population before definitive testing of liver fibrosis by biopsy of the liver. This review provides a systematic overview of these techniques, as well as both direct and indirect biomarkers based approaches used to stage fibrosis and covers recent developments in this rapidly advancing area.

  17. The vitamin E reduces liver lipoperoxidation and fibrosis in a model of nonalcoholic steatohepatitis A vitamina E reduz a lipoperoxidação hepática e a fibrose em modelo experimental de esteatohepatite não-alcoólica

    Directory of Open Access Journals (Sweden)

    Idilio Zamin Jr

    2010-03-01

    Full Text Available CONTEXT: No effective treatment is available for nonalcoholic steatohepatitis in nowadays. OBJECTIVES: To develop a model of nonalcoholic steatohepatitis induced by a methionine and choline deficient diet, as well as to evaluate the role of metformin, vitamin E and simvastatin in the nonalcoholic steatohepatitis progression. METHODS: The study analyzed prospectively 50 Wistar rats for a 90-day period and divided them into five groups of 10 rats. One group was given standard rat diet and the others received the methionine and choline deficient diet. Among the four groups that received this diet, one received saline 0,9% and the others received metformin, vitamin E or simvastatin. After the study period, the animals were sacrificed and their blood was collected for biochemical analysis. The livers were removed for lipoperoxidation analysis and for the histological examinations. RESULTS: The methionine and choline deficient diet was able to induce steatosis in 100% of the animals and nonalcoholic steatohepatitis in 27 (69.2%. The alanine aminotransferase levels were significantly higher in the simvastatin group. The aspartate aminotransferase levels were also higher in the simvastatin group, but were statistically significant only in relation to the standard diet group. When lipoperoxidation values were compared, the groups that received standard rat diet and methionine and choline deficient with vitamin E presented significantly lower rates than the others. The presence of fibrosis was significantly smaller in the group receiving vitamin E. CONCLUSIONS: The diet used was able to induce steatosis and nonalcoholic steatohepatitis. Besides vitamin E showed to reduce the liver oxidative stress, as well as the fibrosis developmentCONTEXTO: Ainda não há um tratamento comprovadamente eficaz para a esteatohepatite não-alcoólica. OBJETIVO: Desenvolver um modelo experimental de esteatohepatite não-alcoólica induzida por dieta deficiente em metionina e

  18. Fibrosis is not just fibrosis - basement membrane modelling and collagen metabolism differs between hepatitis B- and C-induced injury

    DEFF Research Database (Denmark)

    Nielsen, M J; Karsdal, Morten A; Kazankov, K

    2016-01-01

    BACKGROUND: While morphological patterns differ, the molecular phenotype of liver fibrosis is considered a stereotypical response to chronic liver injury. However, with different cellular triggers and networks regulating fibrosis, the molecular responses of the injured liver may not be identical...

  19. [Endomyocardial fibrosis with massive calcification of the left ventricle].

    Science.gov (United States)

    Trigo, Joana; Camacho, Ana; Gago, Paula; Candeias, Rui; Santos, Walter; Marques, Nuno; Matos, Pedro; Brandão, Victor; Gomes, Veloso

    2010-03-01

    Endomyocardial fibrosis is a rare disease, endemic in tropical countries. It is characterized by fibrosis of the endocardium that can extend to myocardium. Important calcification of the endocardium is rare with only a few cases reported in the literature. We report a case of endomyocardial fibrosis in a european caucasian patient, associated with massive calcification of left ventricle.

  20. Living with Cystic Fibrosis: A Guide for the Young Adult.

    Science.gov (United States)

    Cystic Fibrosis Foundation, Atlanta, GA.

    Intended for the young adult with cystic fibrosis, the booklet provides information on dealing with problems and on advances in treatment and detection related to the disease. Addressed are the following topics: description of cystic fibrosis; inheritance of cystic fibrosis; early diagnosis; friends, careers, and other matters; treatment;…

  1. 78 FR 26681 - Medical Criteria for Evaluating Cystic Fibrosis

    Science.gov (United States)

    2013-05-07

    ... ADMINISTRATION RIN 0960-AF58 Medical Criteria for Evaluating Cystic Fibrosis AGENCY: Social Security....04 to evaluate claims involving cystic fibrosis in adults and children under titles II and XVI of the... information on the disability program. 2. Information for individuals with cystic fibrosis who apply for...

  2. Doxycycline Attenuated Pulmonary Fibrosis Induced by Bleomycin in Mice

    OpenAIRE

    Fujita, Masaki; Ye, Qing; Ouchi, Hiroshi; Harada, Eiji; Inoshima, Ichiro; Kuwano, Kazuyoshi; Nakanishi, Yoichi

    2006-01-01

    The administration of doxycycline prior to bleomycin in mice attenuated pulmonary fibrosis. Bronchoalveolar neutrophil influx and gelatinase activity, but not caseinolytic activity, were attenuated by doxycycline. Established fibrosis was not affected by doxycycline. Thus, doxycycline might be useful for slowing down pulmonary fibrosis by biological activity other than antibacterial activity.

  3. Retroperitoneal fibrosis with normal intravenous urogram.

    Science.gov (United States)

    Creagh, F. M.; Stone, T.; Stephenson, T. P.; Lazarus, J. H.

    1985-01-01

    A 58 year old male presented with a two week history of low back pain and malaise. The intravenous urogram (IVU) at presentation was normal but within three months he had developed renal failure with bilateral ureteric obstruction on repeat IVU. Primary retroperitoneal fibrosis was confirmed at operation. This case demonstrates that retroperitoneal fibrosis may progress rapidly to renal failure within a few months of the first symptoms. In addition, the IVU may be normal in the early stages of the illness. Images Figure 1 Figure 2 PMID:3983053

  4. Angiotensinogen Gene Transcription in Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Bruce D. Uhal

    2012-01-01

    Full Text Available An established body of literature supports the hypothesis that activation of a local tissue angiotensin (ANG system in the extravascular tissue compartment of the lungs is required for lung fibrogenesis. Transcriptional activation of the angiotensinogen (AGT gene is believed to be a critical and necessary step in this activation. This paper summarizes the data in support of this theory and discusses transcriptional regulation of AGT, with an emphasis on lung AGT synthesis as a determinant of fibrosis severity. Genetic data linking AGT polymorphisms to the severity of disease in Idiopathic Pulmonary Fibrosis are also discussed.

  5. The cystic fibrosis of exocrine pancreas

    DEFF Research Database (Denmark)

    Wilschanski, Michael; Novak, Ivana

    2013-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) protein is highly expressed in the pancreatic duct epithelia and permits anions and water to enter the ductal lumen. This results in an increased volume of alkaline fluid allowing the highly concentrated proteins secreted by the acinar...... cells to remain in a soluble state. This work will expound on the pathophysiology and pathology caused by the malfunctioning CFTR protein with special reference to ion transport and acid-base abnormalities both in humans and animal models. We will also discuss the relationship between cystic fibrosis...

  6. The Role of PPARs in Lung Fibrosis

    Directory of Open Access Journals (Sweden)

    Heather F. Lakatos

    2007-01-01

    wound healing. PPARβ/δ agonists inhibit lung fibroblast proliferation and enhance the antifibrotic properties of PPARγ agonists. PPARγ ligands oppose the profibrotic effect of TGF-β, which induces differentiation of fibroblasts to myofibroblasts, a critical effector cell in fibrosis. PPARγ ligands, including the thiazolidinedione class of antidiabetic drugs, effectively inhibit lung fibrosis in vitro and in animal models. The clinical availability of potent and selective PPARα and PPARγ agonists should facilitate rapid development of successful treatment strategies based on current and ongoing research.

  7. Management Issues for Adolescents with Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Adelaide Lindsay Withers

    2012-01-01

    Full Text Available The healthy adolescent will encounter major changes in biological and psychosocial domains. The adolescent period can be greatly affected by a chronic illness. Cystic fibrosis is a terminal illness that can significantly affect an adolescent’s biological, mental and psychosocial health. This paper discusses general issues to consider when managing an adolescent with a chronic medical condition, and specifically how cystic fibrosis may impact upon puberty, body image, risk-taking behaviours, mental health, independence, nonadherence, reproductive health, transition, lung transplantation, and end of life care.

  8. A time for multi-scale modeling of anti-fibrotic therapies. Comment on "Towards a unified approach in the modeling of fibrosis: A review with research perspectives" by Martine Ben Amar and Carlo Bianca

    Science.gov (United States)

    Wu, Min

    2016-07-01

    The development of anti-fibrotic therapies in diversities of diseases becomes more and more urgent recently, such as in pulmonary, renal and liver fibrosis [1,2], as well as in malignant tumor growths [3]. As reviewed by Ben Amar and Bianca [4], various theoretical, experimental and in-silico models have been developed to understand the fibrosis process, where the implication on therapeutic strategies has also been frequently demonstrated (e.g., [5-7]). In [4], these models are analyzed and sorted according to their approaches, and in the end of [4], a unified multi-scale approach was proposed to understand fibrosis. While one of the major purposes of extensive modeling of fibrosis is to shed light on therapeutic strategies, the theoretical, experimental and in-silico studies of anti-fibrosis therapies should be conducted more intensively.

  9. Estudo comparativo entre concentrações de bupivacaína a 0,125% e a 0,25% associada ao fentanil para analgesia de parto por via peridural Estudio comparativo entre concentraciones de bupivacaína a 0,125% y a 0,25% asociada al fentanil para analgesia de parto por vía peridural Comparison between 0.125% and 0.25% bupivacaine associated to fentanyl for epidural labor analgesia

    Directory of Open Access Journals (Sweden)

    Marcos Emanuel Wortmann Gomes

    2004-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A analgesia de parto tem a finalidade de diminuir ou até excluir o sofrimento materno durante o trabalho de parto, sendo considerada um método seguro e efetivo para o alívio da dor. O objetivo deste trabalho foi comparar duas concentrações de bupivacaína (0,25% e 0,125%, associada ao fentanil na analgesia de parto por via peridural, quanto à eficácia antálgica e o grau de bloqueio motor, e verificar a influência das diferentes concentrações utilizadas na duração do trabalho de parto, no bem estar do recém-nascido e na satisfação materna. MÉTODO: Neste estudo prospectivo e duplamente encoberto, 51 gestantes primíparas foram distribuídas aleatoriamente em dois grupos para receberem uma de duas concentrações de bupivacaína para indução de analgesia de parto (0,25% [n = 23] ou 0,125% [n = 28]. Para a mensuração da analgesia, foi utilizado a escala numérica de dor, e para a avaliação do bloqueio motor, a escala de Bromage. Para a comparação das médias, foi utilizado o teste t de Student, e, para a comparação das proporções, o teste Qui-quadrado, com p JUSTIFICATIVA Y OBJETIVOS: La analgesia de parto tiene la finalidad de disminuir, o hasta excluir el sufrimiento materno durante el trabajo de parto, siendo considerada un método seguro y efectivo para el alivio del dolor. El objetivo de este trabajo fue comparar dos concentraciones de bupivacaína (0,25% e 0,125%, asociada al fentanil en la analgesia de parto por vía peridural, cuanto a la eficacia antálgica y el grado de bloqueo motor, y verificar la influencia de las diferentes concentraciones utilizadas en la duración del trabajo de parto, en el bien estar del recién-nacido y en la satisfacción materna. MÉTODO: En este estudio prospectivo y duplamente encubierto, 51 gestantes primíparas fueron distribuidas aleatoriamente en dos grupos para recibir una de dos concentraciones de bupivacaína para inducción de analgesia de parto

  10. Submucosa precedes lamina propria in initiating fibrosis in Oral submucous fibrosis - Evidence based on collagen histochemistry

    OpenAIRE

    Rajendran, R; Joseph, Anna P.

    2010-01-01

    Oral submucous fibrosis is a chronic insidious disease and a well-recognized potentially malignantcondition of the oral cavity. It is a collagen related disorder associated with betel quid chewing andcharacterized by progressive hyalinization of the lamina propria.Objectives: It is traditionally held that in oral submucous fibrosis the hyalinization process starts fromthe lamina propria and progresses to involve the submucosal tissues. However reports of someinvestigators suggest that on the ...

  11. Asbestos-related pleural and lung fibrosis in patients with retroperitoneal fibrosis

    Directory of Open Access Journals (Sweden)

    Saha Heikki

    2008-11-01

    Full Text Available Abstract Background Retroperitoneal fibrosis (RPF is a rare fibroinflammatory disease that leads to hydronephrosis and renal failure. In a case-control study, we have recently shown that asbestos exposure was the most important risk factor for RPF in the Finnish population. The aim of this study was to evaluate the relation of asbestos exposure to radiologically confirmed lung and pleural fibrosis among patients with RPF. Methods Chest high-resolution computed tomography (HRCT was performed on 16 unexposed and 22 asbestos-exposed RPF patients and 18 asbestos-exposed controls. Parietal pleural plaques (PPP, diffuse pleural thickening (DPT and parenchymal fibrosis were scored separately. Results Most of the asbestos-exposed RPF patients and half of the asbestos-exposed controls had bilateral PPP, but only a few had lung fibrosis. Minor bilateral plaques were detected in two of the unexposed RPF patients, and none had lung fibrosis. DPT was most frequent and thickest in the asbestos-exposed RPF-patients. In three asbestos-exposed patients with RPF we observed exceptionally large pleural masses that were located anteriorly in the pleural space and continued into the anterior mediastinum. Asbestos exposure was associated with DPT in comparisons between RPF patients and controls (case-control analysis as well as among RPF patients (case-case analysis. Conclusion The most distinctive feature of the asbestos-exposed RPF patients was a thick DPT. An asbestos-related pleural finding was common in the asbestos-exposed RPF patients, but only a few of these patients had parenchymal lung fibrosis. RPF without asbestos exposure was not associated with pleural or lung fibrosis. The findings suggest a shared etiology for RPF and pleural fibrosis and furthermore possibly a similar pathogenetic mechanisms.

  12. Asbestos-related pleural and lung fibrosis in patients with retroperitoneal fibrosis.

    Science.gov (United States)

    Uibu, Toomas; Järvenpää, Ritva; Hakomäki, Jari; Auvinen, Anssi; Honkanen, Eero; Metsärinne, Kaj; Roto, Pekka; Saha, Heikki; Uitti, Jukka; Oksa, Panu

    2008-11-13

    Retroperitoneal fibrosis (RPF) is a rare fibroinflammatory disease that leads to hydronephrosis and renal failure. In a case-control study, we have recently shown that asbestos exposure was the most important risk factor for RPF in the Finnish population. The aim of this study was to evaluate the relation of asbestos exposure to radiologically confirmed lung and pleural fibrosis among patients with RPF. Chest high-resolution computed tomography (HRCT) was performed on 16 unexposed and 22 asbestos-exposed RPF patients and 18 asbestos-exposed controls. Parietal pleural plaques (PPP), diffuse pleural thickening (DPT) and parenchymal fibrosis were scored separately. Most of the asbestos-exposed RPF patients and half of the asbestos-exposed controls had bilateral PPP, but only a few had lung fibrosis. Minor bilateral plaques were detected in two of the unexposed RPF patients, and none had lung fibrosis. DPT was most frequent and thickest in the asbestos-exposed RPF-patients. In three asbestos-exposed patients with RPF we observed exceptionally large pleural masses that were located anteriorly in the pleural space and continued into the anterior mediastinum.Asbestos exposure was associated with DPT in comparisons between RPF patients and controls (case-control analysis) as well as among RPF patients (case-case analysis). The most distinctive feature of the asbestos-exposed RPF patients was a thick DPT. An asbestos-related pleural finding was common in the asbestos-exposed RPF patients, but only a few of these patients had parenchymal lung fibrosis. RPF without asbestos exposure was not associated with pleural or lung fibrosis. The findings suggest a shared etiology for RPF and pleural fibrosis and furthermore possibly a similar pathogenetic mechanisms.

  13. Progressive fibrosis of the quadriceps muscle FIBROSIS PROGRESIVA DEL CUÁDRICEPS

    OpenAIRE

    Enrique Vergara-Amador; Jorge Andrés Largo González

    2011-01-01

    Background. Fibrosis of the quadriceps in children is a frequently reported pathology which is associated with antibiotics having been injected into the thigh. This study presents a series of patients having a common background of having had a single pentavalent vaccine dose or injectable vitamin K and presenting progressive fibrosis of the quadriceps muscle. Materials and methods. Seven children were found who had progressive unilateral retraction of the knee. Six of them had a background of...

  14. Estudo comparativo entre anestesia peridural torácica e anestesia geral em mastectomia oncológica Estudio comparativo entre la anestesia epidural torácica y la anestesia general en mastectomia oncológica Comparative study between thoracic epidural block and general anesthesia for oncologic mastectomy

    Directory of Open Access Journals (Sweden)

    Sérgio D. Belzarena

    2008-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A anestesia peridural torácica é utilizada com freqüência para procedimentos estéticos da mama e há poucos relatos de seu emprego para mastectomias com exploração axilar. O presente estudo comparou a técnica com anestesia geral em operações oncológicas da mama. MÉTODO: Quarenta pacientes foram divididas em dois grupos. No grupo peridural (n = 20 foi realizada peridural torácica com bupivacaína e fentanil associada à sedação com midazolam. O outro grupo (n = 20 recebeu anestesia geral convencional com propofol, atracúrio e fentanil e manutenção com O2 e isoflurano. Registraram-se no intra-operatório duração da operação, necessidade de complementação da anestesia ou da sedação e variáveis hemodinâmicas. No pós-operatório, foram registrados o tempo para alta da sala de recuperação pós-anestésica e hospitalar, a intensidade da dor e o consumo de analgésicos, os efeitos adversos e a satisfação com a técnica anestésica. RESULTADOS: Os grupos foram semelhantes e não houve diferença na duração da operação. Foi necessário complementar a sedação em 100% das pacientes que receberam anestesia peridural e em 15% foi complementada a analgesia com infiltração de anestésico local na axila. Houve maior incidência de hipertensão arterial no grupo da anestesia geral e de hipotensão entre as que receberam peridural. Ocorreu prurido em 55% das pacientes com anestesia peridural. Náusea (30% e vômito (45% foram mais freqüentes entre as que receberam anestesia geral. A analgesia pós-operatória teve melhor qualidade e o consumo de analgésicos foi menor no grupo da anestesia peridural. O período de internação também foi menor. CONCLUSÕES: A técnica peridural tem algumas vantagens com relação à anestesia geral e pode ser considerada uma opção para anestesia em mastectomias oncológicas com esvaziamento axilar.JUSTIFICATIVA Y OBJETIVOS: La anestesia epidural torácica se

  15. Endomyocardial fibrosis associated with Schistosoma Haematobium ...

    African Journals Online (AJOL)

    Endomyocardial fibrosis (EMF) is a form of restrictive cardiomyopathy common in the tropics and subtropics. The aetiology of EMF is unknown but helminth infestations such as schistosomiasis have been implicated. Two boys aged 8 and 10 years with EMF associated with Schistosoma haematobium, are described.

  16. Inhalation of antibiotics in cystic fibrosis

    NARCIS (Netherlands)

    Touw, D J; Brimicombe, R W; Hodson, M E; Heijerman, H G; Bakker, W

    Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis. However, its contribution to the improvement of lung function, infection and quality of life is not well-established. All articles published from 1965 until the present time concerning the inhalation of

  17. Early lung disease in cystic fibrosis.

    Science.gov (United States)

    Grasemann, Hartmut; Ratjen, Felix

    2013-04-01

    Lung disease in patients with cystic fibrosis is characterised by inflammation and recurrent and chronic infections leading to progressive loss in pulmonary function and respiratory failure. Early management of disease results in substantially improved pulmonary function at first testing (at roughly 6 years of age), but the annual decline in pulmonary function tests in older patients has remained unchanged showing how important the early years are in the disease process. Treatment regimens for patients with cystic fibrosis have changed from predominantly symptomatic treatment to preventive or causal (ie, treatments that address the underlying mechanisms of disease) therapeutic interventions. The infant and preschool age (2-5 years) could represent a unique period of opportunity to postpone or even prevent the onset of cystic fibrosis lung disease. We summarise the current knowledge and the methods used to characterise and quantify early lung disease. We discuss treatment strategies including new drugs that are being developed and their potential role in the treatment of early lung disease in patients with cystic fibrosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Prognosis in Cystic Fibrosis: Trends and Predictors

    NARCIS (Netherlands)

    Slieker, M.G.

    2008-01-01

    Cystic fibrosis (CF) is a multisystem disease affecting the digestive system, sweat glands, and the reproductive tract, but progressive lung disease continues to be the major cause of morbidity and mortality. Patients develop chronic infection of the respiratory tract with a characteristic array of

  19. The role of apoptosis in pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    B. D. Uhal

    2008-12-01

    Full Text Available Apoptosis has been defined as "gene-directed cellular self-destruction" and is an active process that is tightly regulated by a number of gene products, which promote or block cell death. Apoptotic death can be triggered by a wide variety of stimuli and, importantly, not all cells necessarily undergo apoptosis in response to the same stimulus. Abnormal regulation of apoptosis has been implicated in a wide range of diseases and approaches to modifying apoptosis represent important future therapeutic strategies. Idiopathic pulmonary fibrosis (IPF is a progressive and relentless disease involving scarring of the lung, which has been recognised as the most lethal interstitial lung disease. In the lungs of IPF patients, increased epithelial apoptosis, together with decreased apoptosis of myofibroblasts, represents persistent findings (particularly in areas of collagen deposition supporting an interaction between altered apoptosis and the pathogenesis of the disease. Data from human tissues and animal models are refining current knowledge of the processes involved in this pathogenesis. This has challenged the dogma that IPF is purely a disease of unresolved inflammation by emphasising the central roles played by the alveolar epithelial cell and myofibroblasts and, as part of that role, the importance of altered apoptosis. Evidence suggests blockade of epithelial cell apoptosis can prevent subsequent collagen deposition, and induction of myofibroblast apoptosis, at least theoretically, would be expected to resolve ongoing fibrosis. These two concepts raise the prospect of therapeutic intervention aimed at modifying apoptosis and, thus, fibrosis in idiopathic pulmonary fibrosis.

  20. Nutritional assessment in children with cystic fibrosis

    Science.gov (United States)

    Optimal nutrition, including consuming 35–40% of calories (kcal) as fat, is a vital part of the management of cystic fibrosis (CF), and involves accurate assessment of dietary intake. We compared 3 methods of nutritional assessment in 8– to 14-year-old children (n=20) with CF: 1) a 24-h Dietary Reca...

  1. Cystic fibrosis year in review 2016.

    Science.gov (United States)

    Savant, Adrienne P; McColley, Susanna A

    2017-08-01

    In this article, we highlight cystic fibrosis (CF) research and case reports published in Pediatric Pulmonology during 2016. We also include articles from a variety of journals that are thematically related to these articles, or are of special interest to clinicians. © 2017 Wiley Periodicals, Inc.

  2. Zinc supplementation in children with cystic fibrosis

    Science.gov (United States)

    Cystic fibrosis (CF) leads to malabsorption of macro- and micronutrients. Symptomatic zinc deficiency has been reported in CF but little is known about zinc homeostasis in children with CF. Zinc supplementation (Zn suppl) is increasingly common in children with CF but it is not without theoretcial r...

  3. Cellular and Molecular Mediators of Intestinal Fibrosis.

    Science.gov (United States)

    Lawrance, Ian C; Rogler, Gerhard; Bamias, Giorgos; Breynaert, Christine; Florholmen, Jon; Pellino, Gianluca; Reif, Shimon; Speca, Silvia; Latella, Giovanni

    2015-11-02

    Intestinal fibrosis is a major complication of the inflammatory bowel diseases (IBD) and although inflammation is necessary for its development, it would appear that it plays a minor role in its progression as anti-inflammatory treatments in IBD do not prevent fibrosis once it has started. The processes that regulate fibrosis would thus appear to be distinct from those regulating inflammation and, therefore, a detailed understanding of these pathways is vital to the development of anti-fibrogenic strategies. There have been several recent reviews exploring what is known, and what remains unknown, about the development of intestinal fibrosis. This review is designed to add to this literature but with a focus on the cellular components that are involved in the development of fibrogenesis and the major molecular mediators that impact on these cells. The aim is to heighten the understanding of the factors involved in intestinal fibrogenesis so that detailed research can be encouraged in order to advance the processes that could lead to effective treatments. © 2014 Published on behalf of European Crohn’s and Colitis Organisation.

  4. Nephrogenic systemic fibrosis: late skin manifestations

    DEFF Research Database (Denmark)

    Bangsgaard, Nannie; Marckmann, Peter; Rossen, Kristian

    2009-01-01

    BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a serious disease that occurs in patients with severe renal disease and is believed to be caused by gadolinium-containing contrast agents. A detailed description of the late skin manifestations of NSF is important to help dermatologists and nephr...

  5. MYOCARDIAL FIBROSIS IN PATIENTS WITH DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2013-01-01

    Full Text Available The mechanism of myocardial damage in diabetes mellitus is considered. The pathogenesis of myocardial fibrosis, leading to diabetic cardiomyopathy, is described in details. Management tactics aimed at the prevention of heart failure in patients with diabetes is proposed.

  6. Targeting lysyl oxidase reduces peritoneal fibrosis.

    Directory of Open Access Journals (Sweden)

    Christopher R Harlow

    Full Text Available Abdominal surgery and disease cause persistent abdominal adhesions, pelvic pain, infertility and occasionally, bowel obstruction. Current treatments are ineffective and the aetiology is unclear, although excessive collagen deposition is a consistent feature. Lysyl oxidase (Lox is a key enzyme required for crosslinking and deposition of insoluble collagen, so we investigated whether targeting Lox might be an approach to reduce abdominal adhesions.Female C57Bl/6 mice were treated intraperitoneally with multiwalled carbon nanotubes (NT to induce fibrosis, together with chemical (ß-aminoproprionitrile-BAPN or miRNA Lox inhibitors, progesterone or dexamethasone. Fibrotic lesions on the diaphragm, and expression of fibrosis-related genes in abdominal wall peritoneal mesothelial cells (PMC were measured. Effects of BAPN and dexamethasone on collagen fibre alignment were observed by TEM. Isolated PMC were cultured with interleukin-1 alpha (IL-1α and progesterone to determine effects on Lox mRNA in vitro.NT-induced fibrosis and collagen deposition on the diaphragm was ameliorated by BAPN, Lox miRNA, or steroids. BAPN and dexamethasone disrupted collagen fibres. NT increased PMC Lox, Col1a1, Col3a1 and Bmp1 mRNA, which was inhibited by steroids. Progesterone significantly inhibited IL-1α induced Lox expression by PMC in vitro.Our results provide proof-of-concept that targeting peritoneal Lox could be an effective approach in ameliorating fibrosis and adhesion development.

  7. Targeting lysyl oxidase reduces peritoneal fibrosis.

    Science.gov (United States)

    Harlow, Christopher R; Wu, Xuan; van Deemter, Marielle; Gardiner, Fiona; Poland, Craig; Green, Rebecca; Sarvi, Sana; Brown, Pamela; Kadler, Karl E; Lu, Yinhui; Mason, J Ian; Critchley, Hilary O D; Hillier, Stephen G

    2017-01-01

    Abdominal surgery and disease cause persistent abdominal adhesions, pelvic pain, infertility and occasionally, bowel obstruction. Current treatments are ineffective and the aetiology is unclear, although excessive collagen deposition is a consistent feature. Lysyl oxidase (Lox) is a key enzyme required for crosslinking and deposition of insoluble collagen, so we investigated whether targeting Lox might be an approach to reduce abdominal adhesions. Female C57Bl/6 mice were treated intraperitoneally with multiwalled carbon nanotubes (NT) to induce fibrosis, together with chemical (ß-aminoproprionitrile-BAPN) or miRNA Lox inhibitors, progesterone or dexamethasone. Fibrotic lesions on the diaphragm, and expression of fibrosis-related genes in abdominal wall peritoneal mesothelial cells (PMC) were measured. Effects of BAPN and dexamethasone on collagen fibre alignment were observed by TEM. Isolated PMC were cultured with interleukin-1 alpha (IL-1α) and progesterone to determine effects on Lox mRNA in vitro. NT-induced fibrosis and collagen deposition on the diaphragm was ameliorated by BAPN, Lox miRNA, or steroids. BAPN and dexamethasone disrupted collagen fibres. NT increased PMC Lox, Col1a1, Col3a1 and Bmp1 mRNA, which was inhibited by steroids. Progesterone significantly inhibited IL-1α induced Lox expression by PMC in vitro. Our results provide proof-of-concept that targeting peritoneal Lox could be an effective approach in ameliorating fibrosis and adhesion development.

  8. Pirfenidone treatment in idiopathic pulmonary fibrosis

    DEFF Research Database (Denmark)

    Salih, Goran Nadir; Shaker, Saher Burhan; Madsen, Helle Dall

    2016-01-01

    BACKGROUND: Pirfenidone was approved by the European Medicines Agency and introduced in most European countries in 2011 for treatment of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: To describe the national Danish experiences of pirfenidone treatment for IPF during 30 months with respect...

  9. Surfactant protein C in canine pulmonary fibrosis.

    Science.gov (United States)

    Eriksson, M; von Euler, H; Ekman, E; Nordling, K; Häggström, J; Johansson, J

    2009-01-01

    Canine pulmonary fibrosis (CPF) occurs most commonly in West Highland White Terriers. The differing incidences of CPF among dog breeds suggest that genetic factors contribute to its pathophysiology. Pulmonary fibrosis in humans is associated with mutations in the gene coding for lung surfactant protein C (SP-C) (SFTPC). To investigate the histopathologic changes and SP-C composition and genetic structure in dogs with CPF. Five dogs with PF, 2 dogs with other lung diseases, and 3 healthy dogs. Lung tissue from dogs with clinically suspected CPF and 5 control cases was analyzed histopathologically. Bronchoalveolar lavage fluid (BALF) collected postmortem from 3 terriers with histopathologically confirmed pulmonary fibrosis and the 5 controls were analyzed by Western blots, and the exons of SFTPC were sequenced for 2 dogs with PF and 1 dog with other lung disease. SP-C could not be detected in BALF of 1 dog with PF, although SP-B was present. A mutation was detected in SFTPC exon 5 of this dog. From 2 dogs with PF and in all 5 control dogs SP-B and SP-C were detected in BALF. Taken together, the results indicate that canine and human lung fibrosis share histopathologic features and that analysis of SP-C and its gene in a larger set of dogs with PF is warranted.

  10. TECHNICAL NOTE Nephrogenic systemic fibrosis (NSF) and ...

    African Journals Online (AJOL)

    Gadolinium-DTPA (Gd-DTPA), introduced in 1988, is the first paramagnetic contrast agent approved for clinical use in MR imaging. The frequency of adverse reactions is low. Nephrogenic systemic fibrosis (NSF), unknown before March 1997 and first described in. 2000, is a systemic disorder characterised by widespread ...

  11. Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis

    Science.gov (United States)

    Humphreys, Benjamin D.; Xu, Fengfeng; Sabbisetti, Venkata; Grgic, Ivica; Naini, Said Movahedi; Wang, Ningning; Chen, Guochun; Xiao, Sheng; Patel, Dhruti; Henderson, Joel M.; Ichimura, Takaharu; Mou, Shan; Soeung, Savuth; McMahon, Andrew P.; Kuchroo, Vijay K.; Bonventre, Joseph V.

    2013-01-01

    Acute kidney injury predisposes patients to the development of both chronic kidney disease and end-stage renal failure, but the molecular details underlying this important clinical association remain obscure. We report that kidney injury molecule-1 (KIM-1), an epithelial phosphatidylserine receptor expressed transiently after acute injury and chronically in fibrotic renal disease, promotes kidney fibrosis. Conditional expression of KIM-1 in renal epithelial cells (Kim1RECtg) in the absence of an injury stimulus resulted in focal epithelial vacuolization at birth, but otherwise normal tubule histology and kidney function. By 4 weeks of age, Kim1RECtg mice developed spontaneous and progressive interstitial kidney inflammation with fibrosis, leading to renal failure with anemia, proteinuria, hyperphosphatemia, hypertension, cardiac hypertrophy, and death, analogous to progressive kidney disease in humans. Kim1RECtg kidneys had elevated expression of proinflammatory monocyte chemotactic protein-1 (MCP-1) at early time points. Heterologous expression of KIM-1 in an immortalized proximal tubule cell line triggered MCP-1 secretion and increased MCP-1–dependent macrophage chemotaxis. In mice expressing a mutant, truncated KIM-1 polypeptide, experimental kidney fibrosis was ameliorated with reduced levels of MCP-1, consistent with a profibrotic role for native KIM-1. Thus, sustained KIM-1 expression promotes kidney fibrosis and provides a link between acute and recurrent injury with progressive chronic kidney disease. PMID:23979159

  12. Dose-dependent effects of alpha-naphthylisothiocyanate disconnect biliary fibrosis from hepatocellular necrosis.

    Science.gov (United States)

    Joshi, Nikita; Ray, Jessica L; Kopec, Anna K; Luyendyk, James P

    2017-01-01

    Exposure of rodents to the xenobiotic α-naphthylisothiocyanate (ANIT) is an established model of experimental intrahepatic bile duct injury. Administration of ANIT to mice causes neutrophil-mediated hepatocellular necrosis. Prolonged exposure of mice to ANIT also produces bile duct hyperplasia and liver fibrosis. However, the mechanistic connection between ANIT-induced hepatocellular necrosis and bile duct hyperplasia and fibrosis is not well characterized. We examined impact of two different doses of ANIT, by feeding chow containing ANIT (0.05%, 0.1%), on the severity of various liver pathologies in a model of chronic ANIT exposure. ANIT-elicited increases in liver inflammation and hepatocellular necrosis increased with dose. Remarkably, there was no connection between increased hepatocellular necrosis and bile duct hyperplasia and peribiliary fibrosis, as these pathologies increased similarly in mice exposed to either dose of ANIT. The results indicate that the severity of hepatocellular necrosis does not dictate the extent of bile duct hyperplasia/fibrosis in ANIT-exposed mice. © 2016 Wiley Periodicals, Inc.

  13. Endostatin and kidney fibrosis in aging: a case for antagonistic pleiotropy?

    Science.gov (United States)

    Lin, Chi Hua Sarah; Chen, Jun; Ziman, Bruce; Marshall, Shannon; Maizel, Julien

    2014-01-01

    A recurring theme of a host of gerontologic studies conducted in either experimental animals or in humans is related to documenting the functional decline with age. We hypothesize that elevated circulating levels of a powerful antiangiogenic peptide, endostatin, represent one of the potent systemic causes for multiorgan microvascular rarefaction and functional decline due to fibrosis. It is possible that during the life span of an organism there is an accumulation of dormant transformed cells producing antiangiogenic substances (endostatin) that maintain the dormancy of such scattered malignant cells. The proof of this postulate cannot be obtained by physically documenting these scattered cells, and it rests exclusively on the detection of sequelae of shifted pro- and antiangiogenic balance toward the latter. Here we compared circulating levels of endostatin in young and aging mice of two different strains and showed that endostatin levels are elevated in the latter. Renal expression of endostatin increased ∼5.6-fold in aging animals. This was associated with microvascular rarefaction and progressive tubulointerstitial fibrosis. In parallel, the levels of sirtuins 1 and 3 were significantly suppressed in aging mice in conjunction with the expression of markers of senescence. Treating young mice with endostatin for 28 days showed delayed recovery of circulation after femoral artery ligation and reduced patency of renal microvasculature but no fibrosis. In conclusion, the findings are consistent with the hypothesis on elevation of endostatin levels and parallel microvascular rarefaction and induction of renal fibrosis in aging mice. PMID:24727495

  14. Relevance of mouse models of cardiac fibrosis and hypertrophy in cardiac research

    Science.gov (United States)

    Rai, Vikrant; Sharma, Poonam; Agrawal, Swati

    2016-01-01

    Heart disease causing cardiac cell death due to ischemia–reperfusion injury is a major cause of morbidity and mortality in the United States. Coronary heart disease and cardiomyopathies are the major cause for congestive heart failure, and thrombosis of the coronary arteries is the most common cause of myocardial infarction. Cardiac injury is followed by post-injury cardiac remodeling or fibrosis. Cardiac fibrosis is characterized by net accumulation of extracellular matrix proteins in the cardiac inter-stitium and results in both systolic and diastolic dysfunctions. It has been suggested by both experimental and clinical evidence that fibrotic changes in the heart are reversible. Hence, it is vital to understand the mechanism involved in the initiation, progression, and resolution of cardiac fibrosis to design anti-fibrotic treatment modalities. Animal models are of great importance for cardiovascular research studies. With the developing research field, the choice of selecting an animal model for the proposed research study is crucial for its outcome and translational purpose. Compared to large animal models for cardiac research, the mouse model is preferred by many investigators because of genetic manipulations and easier handling. This critical review is focused to provide insight to young researchers about the various mouse models, advantages and disadvantages, and their use in research pertaining to cardiac fibrosis and hypertrophy. PMID:27766529

  15. Anti-profibrotic effects of artesunate on bleomycin-induced pulmonary fibrosis in Sprague Dawley rats.

    Science.gov (United States)

    Wang, Changming; Xuan, Xiuping; Yao, Wenmin; Huang, Guojin; Jin, Junfei

    2015-07-01

    The present study aimed to determine whether artesunate has beneficial effects on bleomycin-induced pulmonary fibrosis in rats and to examine the possible mechanisms underlying these effects. All experiments were performed with male Sprague Dawley rats weighing 180-250 g. Animals were randomly divided into four experimental groups that were administered either saline alone, artesunate alone, bleomycin alone or bleomycin + artesunate. Lung histopathology was investigated by hematoxylin and eosin staining and Masson staining. Lung profibrotic molecules were analyzed by reverse transcription polymerase chain reaction, immunoblotting and immunohistochemistry. In rats treated with artesunate, pulmonary fibrosis induced by bleomycin was significantly reduced. Administration of artesunate significantly improved bleomycin-induced morphological alterations. Profibrotic molecules, including transforming growth factor-β1, Smad3, heat shock protein 47, α-smooth muscle actin and collagen type I were also reduced by artesunate. These findings suggest that artesunate improves bleomycin-induced pulmonary fibrosis pathology in rats possibly by inhibiting profibrotic molecules associated with pulmonary fibrosis.

  16. Targeting Phospholipase D4 Attenuates Kidney Fibrosis.

    Science.gov (United States)

    Trivedi, Priyanka; Kumar, Ramya K; Iyer, Ashwin; Boswell, Sarah; Gerarduzzi, Casimiro; Dadhania, Vivekkumar P; Herbert, Zach; Joshi, Nikita; Luyendyk, James P; Humphreys, Benjamin D; Vaidya, Vishal S

    2017-12-01

    Phospholipase D4 (PLD4), a single-pass transmembrane glycoprotein, is among the most highly upregulated genes in murine kidneys subjected to chronic progressive fibrosis, but the function of PLD4 in this process is unknown. Here, we found PLD4 to be overexpressed in the proximal and distal tubular epithelial cells of murine and human kidneys after fibrosis. Genetic silencing of PLD4, either globally or conditionally in proximal tubular epithelial cells, protected mice from the development of fibrosis. Mechanistically, global knockout of PLD4 modulated innate and adaptive immune responses and attenuated the upregulation of the TGF-β signaling pathway and α1-antitrypsin protein (a serine protease inhibitor) expression and downregulation of neutrophil elastase (NE) expression induced by obstructive injury. In vitro, treatment with NE attenuated TGF-β-induced accumulation of fibrotic markers. Furthermore, therapeutic targeting of PLD4 using specific siRNA protected mice from folic acid-induced kidney fibrosis and inhibited the increase in TGF-β signaling, decrease in NE expression, and upregulation of mitogen-activated protein kinase signaling. Immunoprecipitation/mass spectrometry and coimmunoprecipitation experiments confirmed that PLD4 binds three proteins that interact with neurotrophic receptor tyrosine kinase 1, a receptor also known as TrkA that upregulates mitogen-activated protein kinase. PLD4 inhibition also prevented the folic acid-induced upregulation of this receptor in mouse kidneys. These results suggest inhibition of PLD4 as a novel therapeutic strategy to activate protease-mediated degradation of extracellular matrix and reverse fibrosis. Copyright © 2017 by the American Society of Nephrology.

  17. Analgesia peridural para o trabalho de parto e para o parto: efeitos da adição de um opióide Effects of the association of an opioid with epidural analgesia for labor and delivery

    Directory of Open Access Journals (Sweden)

    José Guilherme Cecatti

    1998-07-01

    Full Text Available O objetivo deste estudo foi avaliar a eficácia e segurança da associação bupivacaína com sufentanil para a analgesia no trabalho de parto e do parto por meio de um bloqueio peridural contínuo. Realizou-se um ensaio clínico duplo-cego, prospectivo e aleatório, incluindo sessenta mulheres nulíparas da Maternidade do CAISM/UNICAMP. No momento da analgesia, as mulheres foram aleatoriamente alocadas em dois grupos: BS, recebendo 12,5 mg de bupivacaína com adrenalina mais 30 µg de sufentanil e BP, recebendo 12,5 mg de bupivacaína com adrenalina mais placebo. Foram avaliados os parâmetros relativos à qualidade e duração da analgesia, duração do trabalho de parto e também possíveis efeitos sobre o recém-nascido. Os resultados mostraram a superioridade da adição do sufentanil sobre o grau de analgesia durante o tempo de ação da primeira dose de anestésico local. Não houve aumento na duração do trabalho de parto depois do início da analgesia quando se compararam ambos os grupos, nem qualquer diferença quanto à via de parto. Não houve também diferenças entre os grupos com relação à avaliação dos recém-nascidos. Conclui-se que a associação de 30 µg de sufentanil à primeira dose de bupivacaína é segura e eficaz, melhorando a qualidade da analgesia, sua duração e não afetando a progressão do trabalho de parto e o resultado neonatal.The purpose of the present study was to evaluate the efficacy and safety of the association bupivacaine with sufentanil for labor and delivery analgesia through a continuous epidural blockade, for both mother and the neonate. A randomized double blind prospective clinical trial was performed including sixty nulliparous women at the Maternity of CAISM/UNICAMP. When requesting analgesia, the women were randomly allocated to two groups: BS, receiving 12.5 mg of bupivacaine with adrenaline plus 30 µg of sufentanil and BP, receiving 12.5 mg of bupivacaine with adrenaline plus placebo

  18. Physical exercise training for cystic fibrosis.

    Science.gov (United States)

    Radtke, Thomas; Nevitt, Sarah J; Hebestreit, Helge; Kriemler, Susi

    2017-11-01

    Physical exercise training may form an important part of regular care for people with cystic fibrosis. This is an update of a previously published review. To assess the effects of physical exercise training on exercise capacity by peak oxygen consumption, pulmonary function by forced expiratory volume in one second, health-related quality of life and further important patient-relevant outcomes in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 04 May 2017.We searched ongoing trials registers (clinicaltrials.gov and the WHO ICTRP). Date of most recent search: 10 August 2017. All randomised and quasi-randomised controlled clinical trials comparing exercise training of any type and a minimum duration of two weeks with conventional care (no training) in people with cystic fibrosis. Two authors independently selected studies for inclusion, assessed methodological quality and extracted data. The quality of the evidence was assessed using the GRADE system. Of the 83 studies identified, 15 studies which included 487 participants, met the inclusion criteria. The numbers in each study ranged from nine up to 72 participants; two studies were in adults, seven were in children and adolescents and six studies included all age ranges. Four studies of hospitalised participants lasted less than one month and 11 studies were outpatient-based, lasting between two months and three years. The studies included participants with a wide range of disease severity and employed differing levels of supervision with a mixture of types of training. There was also wide variation in the quality of the included studies.This systematic review shows very low- to low-quality evidence from both short- and long-term studies that in people

  19. Physical exercise training for cystic fibrosis.

    Science.gov (United States)

    Radtke, Thomas; Nolan, Sarah J; Hebestreit, Helge; Kriemler, Susi

    2015-06-28

    Physical exercise training may form an important part of regular care for people with cystic fibrosis. This is an update of previously published reviews. To determine the effects of physical exercise training compared to no training on aerobic exercise capacity, forced expiratory volume in one second, health-related quality of life and other patient-relevant (secondary) outcomes in cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 10 March 2015. All randomised and quasi-randomised controlled clinical trials comparing exercise training of any type and duration with conventional care in people with cystic fibrosis. Two authors independently selected studies for inclusion, assessed methodological quality and extracted data. Of the 48 studies identified, 13 studies which included 402 participants, met the inclusion criteria. The numbers in each study ranged from nine up to 72 participants; one study was in adults, six were in children and adolescents and six studies included all age ranges. Four studies of hospitalised participants lasted less than one month and nine studies were outpatient-based, lasting between two months and three years. The studies included participants with a wide range of disease severity and employed differing levels of supervision with a mixture of types of training. There was also wide variation in the quality of the included studies.This systematic review shows limited evidence from both short- and long-term studies that in people with cystic fibrosis aerobic or anaerobic physical exercise training or a combination of both has a positive effect on aerobic exercise capacity, pulmonary function and health-related quality of life. Although improvements are not consistent between studies and ranged

  20. Treatment with 4-methylpyrazole modulated stellate cells and natural killer cells and ameliorated liver fibrosis in mice.

    Directory of Open Access Journals (Sweden)

    Hyon-Seung Yi

    Full Text Available Accumulating evidence suggests that retinol and its metabolites are closely associated with liver fibrogenesis. Recently, we demonstrated that genetic ablation of alcohol dehydrogenase 3 (ADH3, a retinol metabolizing gene that is expressed in hepatic stellate cells (HSCs and natural killer (NK cells, attenuated liver fibrosis in mice. In the current study, we investigated whether pharmacological ablation of ADH3 has therapeutic effects on experimentally induced liver fibrosis in mice.Liver fibrosis was induced by intraperitoneal injections of carbon tetrachloride (CCl4 or bile duct ligation (BDL for two weeks. To inhibit ADH3-mediated retinol metabolism, 10 μg 4-methylpyrazole (4-MP/g of body weight was administered to mice treated with CCl4 or subjected to BDL. The mice were sacrificed at week 2 to evaluate the regression of liver fibrosis. Liver sections were stained for collagen and α-smooth muscle actin (α-SMA. In addition, HSCs and NK cells were isolated from control and treated mice livers for molecular and immunological studies.Treatment with 4-MP attenuated CCl4- and BDL-induced liver fibrosis in mice, without any adverse effects. HSCs from 4-MP treated mice depicted decreased levels of retinoic acids and increased retinol content than HSCs from control mice. In addition, the expression of α-SMA, transforming growth factor-β1 (TGF-β1, and type I collagen α1 was significantly reduced in the HSCs of 4-MP treated mice compared to the HSCs from control mice. Furthermore, inhibition of retinol metabolism by 4-MP increased interferon-γ production in NK cells, resulting in increased apoptosis of activated HSCs.Based on our data, we conclude that inhibition of retinol metabolism by 4-MP ameliorates liver fibrosis in mice through activation of NK cells and suppression of HSCs. Therefore, retinol and its metabolizing enzyme, ADH3, might be potential targets for therapeutic intervention of liver fibrosis.

  1. Factors Promoting Development of Fibrosis in Crohn’s Disease

    Directory of Open Access Journals (Sweden)

    Gerhard Rogler

    2017-07-01

    Full Text Available The concepts on the pathophysiology of intestinal fibrosis in Crohn’s disease (CD have changed in recent years. Some years ago fibrosis was regarded to be a consequence of long-standing inflammation with subsequent destruction of the gut wall matrix followed by scar formation and collagen deposition. Fibrosis in CD patients appeared to be an irreversible process that could hardly be influenced. Therefore, the main target in CD therapy was to control inflammation to avoid fibrosis development. Many of these assumptions seem to be only partially true. Inflammation may be a necessary prerequisite for the initiation of fibrosis. However, when the pathophysiologic processes that lead to fibrosis in CD patients have been initiated fibrosis development may be independent of inflammation and may continue even when inflammation is under good medical control. Fibrosis in CD also may be reversible. After strictureplasty local collagen deposits decrease or even disappear. With new animal models for intestinal fibrosis on the horizon, we need to spend more efforts on understanding the factors influencing fibrosis in CD patients to finally find specific therapies. In this context, it will be as important to find markers and quantitative imaging tools to have reliable endpoints for clinical trials in fibrosing CD.

  2. Isquemia miocárdica silenciosa em pacientes submetidos à prostatectomia transuretral: comparação entre anestesia subaracnóidea e peridural Isquemia miocárdica silenciosa en pacientes sometidos a prostatectomia transuretral: comparación entre anestesia subaracnóidea y peridural Silent myocardial ischaemia in patients undergoing transurethral resection of prostate: comparison of spinal versus epidural anaesthesia

    Directory of Open Access Journals (Sweden)

    Parshotam Lal Gautam

    2004-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A isquemia miocárdica silenciosa foi recentemente relacionada ao aumento de morbimortalidade cardíaca peri-operatória. Até 41% dos pacientes com doença coronariana conhecida ou fatores de risco cardíaco, submetidos à cirurgias não cardíacas, apresentaram isquemia peri-operatória. Vários autores compararam técnicas de anestesia regional e geral mas nenhum comparou o impacto de diferentes técnicas de anestesia no neuro-eixo na incidência e duração da isquemia miocárdica silenciosa. O objetivo deste estudo foi comparar duas técnicas diferentes de anestesia no neuro-eixo (subaracnóidea versus peridural em pacientes idosos aleatoriamente selecionados e submetidos à prostatectomia transuretral. Optou-se por este grupo de pacientes idosos porque freqüentemente, apresentam doença coronariana silenciosa ou clinicamente aparente. Um outro fator importante que influenciou a escolha, foi a sobrecarga de volume e tremores causados pela prostatectomia transuretral nesses pacientes promovendo desequilíbrio entre consumo e oferta de oxigênio. MÉTODO: Participaram deste estudo 40 pacientes submetidos a prostatectomia transuretral, que foram estudados em relação à isquemia miocárdica silenciosa com a ajuda de um equipamento Holter. A monitorização iniciou-se 1 hora antes da cirurgia, prosseguiu durante a cirurgia e após pelas próximas 24 horas. Os dados do Holter foram analisados por um DSM modelo 300. RESULTADOS: A incidência geral de isquemia miocárdica silenciosa neste estudo foi de 30%. Não foi estabelecida nenhuma relação entre isquemia miocárdica silenciosa e o tipo de anestesia. A maior parte dos episódios de isquemia miocárdica ocorreu no período pré-operatório e não tiveram relação com alterações hemodinâmicas. No entanto, a incidência e a gravidade de isquemia miocárdica silenciosa foi mais alta em pacientes com altos escores de Detsky, hipertensão arterial e anemia. Nenhum

  3. Systems genetics of liver fibrosis: identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population.

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    Rabea A Hall

    Full Text Available The progression of liver fibrosis in response to chronic injury varies considerably among individual patients. The underlying genetics is highly complex due to large numbers of potential genes, environmental factors and cell types involved. Here, we provide the first toxicogenomic analysis of liver fibrosis induced by carbon tetrachloride in the murine 'genetic reference panel' of recombinant inbred BXD lines. Our aim was to define the core of risk genes and gene interaction networks that control fibrosis progression. Liver fibrosis phenotypes and gene expression profiles were determined in 35 BXD lines. Quantitative trait locus (QTL analysis identified seven genomic loci influencing fibrosis phenotypes (pQTLs with genome-wide significance on chromosomes 4, 5, 7, 12, and 17. Stepwise refinement was based on expression QTL mapping with stringent selection criteria, reducing the number of 1,351 candidate genes located in the pQTLs to a final list of 11 cis-regulated genes. Our findings demonstrate that the BXD reference population represents a powerful experimental resource for shortlisting the genes within a regulatory network that determine the liver's vulnerability to chronic injury.

  4. The Human Amnion Epithelial Cell Secretome Decreases Hepatic Fibrosis in Mice with Chronic Liver Fibrosis

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    Majid Alhomrani

    2017-10-01

    Full Text Available Background: Hepatic stellate cells (HSCs are the primary collagen-secreting cells in the liver. While HSCs are the major cell type involved in the pathogenesis of liver fibrosis, hepatic macrophages also play an important role in mediating fibrogenesis and fibrosis resolution. Previously, we observed a reduction in HSC activation, proliferation, and collagen synthesis following exposure to human amnion epithelial cells (hAEC and hAEC-conditioned media (hAEC-CM. This suggested that specific factors secreted by hAEC might be effective in ameliorating liver fibrosis. hAEC-derived extracellular vesicles (hAEC-EVs, which are nanosized (40–100 nm membrane bound vesicles, may act as novel cell–cell communicators. Accordingly, we evaluated the efficacy of hAEC-EV in modulating liver fibrosis in a mouse model of chronic liver fibrosis and in human HSC.Methods: The hAEC-EVs were isolated and characterized. C57BL/6 mice with CCl4-induced liver fibrosis were administered hAEC-EV, hAEC-CM, or hAEC-EV depleted medium (hAEC-EVDM. LX2 cells, a human HSC line, and bone marrow-derived mouse macrophages were exposed to hAEC-EV, hAEC-CM, and hAEC-EVDM. Mass spectrometry was used to examine the proteome profile of each preparation.Results: The extent of liver fibrosis and number of activated HSCs were reduced significantly in CCl4-treated mice given hAEC-EVs, hAEC-CM, and hAEC EVDM compared to untreated controls. Hepatic macrophages were significantly decreased in all treatment groups, where a predominant M2 phenotype was observed. Human HSCs cultured with hAEC-EV and hAEC-CM displayed a significant reduction in collagen synthesis and hAEC-EV, hAEC-CM, and hAEC-EVDM altered macrophage polarization in bone marrow-derived mouse macrophages. Proteome analysis showed that 164 proteins were unique to hAEC-EV in comparison to hAEC-CM and hAEC-EVDM, and 51 proteins were co-identified components with the hAEC-EV fraction.Conclusion: This study provides novel data

  5. Lymphoplasmacytic Sclerosing Pancreatitis and Retroperitoneal Fibrosis

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    Nigel K. F. Koo Ng

    2008-01-01

    Full Text Available Although cases of lymphoplasmacytic sclerosing pancreatitis (LSP associated with idiopathic retroperitoneal fibrosis have been reported, the association is rare. We describe a 74-year-old man who presented with obstructive jaundice and weight loss. Nineteen months earlier, he had been diagnosed with idiopathic retroperitoneal fibrosis and treated with bilateral ureteric stents. Initial investigations were suggestive of a diagnosis of LSP, however, a malignant cause could not be ruled out. He underwent an exploratory laparotomy and frozen sections confirmed the diagnosis of LSP. An internal biliary bypass was performed using a Roux loop of jejunum, and the patient made an uneventful recovery. This case illustrates the difficulty in distinguishing LSP from pancreatic carcinoma preoperatively.

  6. Idiopathic Pulmonary Fibrosis: Treatment and Prognosis

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    Hajime Fujimoto

    2015-01-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a chronic progressive lung disease with a prognosis that can be worse than for many cancers. The initial stages of the condition were thought to mainly involve chronic inflammation; therefore, corticosteroids and other drugs that have anti-inflammatory and immunosuppressive actions were used. However, recently, agents targeting persistent fibrosis resulting from aberrant repair of alveolar epithelial injury have been in the spotlight. There has also been an increase in the number of available antifibrotic treatment options, starting with pirfenidone and nintedanib. These drugs prevent deterioration but do not improve IPF. Therefore, nonpharmacologic approaches such as long-term oxygen therapy, pulmonary rehabilitation, and lung transplantation must be considered as additional treatment modalities.

  7. Congenital Fibrosis of the Extraocular Muscles

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    Leyla Niyaz

    2014-08-01

    Full Text Available Congenital fibrosis of the extraocular muscles (CFEOM is a rare disorder characterized by hereditary non-progressive restrictive strabismus and blepharoptosis. Although most of the cases are bilateral and isolated, some patients may have systemic findings. CFEOM is divided into three groups as CFEOM 1, 2, and 3 according to the phenotype. Primary responsible genes are KIF21A for CFEOM type 1 and 3 and PHOX2A/ARIX gene for CFEOM type 2. Studies suggest that abnormal innervation of the extraocular muscles is the cause of muscle fibrosis. Early treatment is important because of the risk of amblyopia. Surgery is the primary treatment option for strabismus and blepharoptosis. (Turk J Ophthalmol 2014; 44: 312-5

  8. Cystic fibrosis and physiological responses to exercise.

    Science.gov (United States)

    Williams, Craig A; Saynor, Zoe L; Tomlinson, Owen W; Barker, Alan R

    2014-12-01

    Cardiopulmonary exercise testing is underutilized within the clinical management of patients with cystic fibrosis. But within the last 5 years, there has been considerable interest in its implementation, which has included deliberations by the European Cystic Fibrosis Society about incorporating this method within the clinical assessment of patients. This review examines the current use of cardiopulmonary exercise testing in assessing the extent and cause(s) of exercise limitation from a pediatric perspective. Examples of the measured parameters and their interpretation are provided. Critical synthesis of recent work in the oxygen uptake (VO2) kinetics response to and following exercise is also discussed, and although identified more as a research tool, its utilization advances researchers understanding of the cardiovascular, respiratory and muscular limitations to exercise tolerance. Finally, exercise and its application in therapeutic interventions are highlighted and a number of recommendations made about the utility of exercise prescription.

  9. Macrophages in tissue repair, regeneration, and fibrosis

    Science.gov (United States)

    Wynn, Thomas A.; Vannella, Kevin M.

    2016-01-01

    Inflammatory monocytes and resident tissue macrophages are key regulators of tissue repair, regeneration, and fibrosis. Following tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play critical roles during the initiation, maintenance, and resolution phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, with uncontrolled inflammatory mediator and growth factor production, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contributing to a state of persistent injury, which may lead to the development of pathological fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue regenerating phenotypes following injury, and highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically. PMID:26982353

  10. [Endomyocardial fibrosis (its clinico-echocardiographic characteristics)].

    Science.gov (United States)

    Bapumiia, M; Solomakhina, N I; Sumarokov, A V

    1996-01-01

    To compare clinical and echocardiographic features in patients with restrictive cardiomyopathy (RCMP), 15 patients (9 males and 6 females, mean age 34.93 +/- 1.03 years, duration of the disease 9 +/- 4.2 months) were examined using complete echocardiographic and doppler echocardiographic investigation in impulse regimen. Endomyocardial fibrosis was not obvious clinically, but should be suspected in dyspnea upon a weak exercise, undue fatiguability, tachycardia in normal arterial pressure and size of the heart. Echocardiographic indications, on the contrary, were rather specific. Endomyocardial fibrosis is characterized by diminished ventricular cavities, thickening of the endocardium and subvalvular structures, changed shape of ventricular cavity, echo-CG signs of passive pulmonary hypertension, diastolic dysfunction of the left and right ventricles.

  11. Painful connections: densification versus fibrosis of fascia.

    Science.gov (United States)

    Pavan, Piero G; Stecco, Antonio; Stern, Robert; Stecco, Carla

    2014-01-01

    Deep fascia has long been considered a source of pain, secondary to nerve pain receptors becoming enmeshed within the pathological changes to which fascia are subject. Densification and fibrosis are among such changes. They can modify the mechanical properties of deep fasciae and damage the function of underlying muscles or organs. Distinguishing between these two different changes in fascia, and understanding the connective tissue matrix within fascia, together with the mechanical forces involved, will make it possible to assign more specific treatment modalities to relieve chronic pain syndromes. This review provides an overall description of deep fasciae and the mechanical properties in order to identify the various alterations that can lead to pain. Diet, exercise, and overuse syndromes are able to modify the viscosity of loose connective tissue within fascia, causing densification, an alteration that is easily reversible. Trauma, surgery, diabetes, and aging alter the fibrous layers of fasciae, leading to fascial fibrosis.

  12. Cyclic Nucleotide Signalling in Kidney Fibrosis

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    Elisabeth Schinner

    2015-01-01

    Full Text Available Kidney fibrosis is an important factor for the progression of kidney diseases, e.g., diabetes mellitus induced kidney failure, glomerulosclerosis and nephritis resulting in chronic kidney disease or end-stage renal disease. Cyclic adenosine monophosphate (cAMP and cyclic guanosine monophosphate (cGMP were implicated to suppress several of the above mentioned renal diseases. In this review article, identified effects and mechanisms of cGMP and cAMP regarding renal fibrosis are summarized. These mechanisms include several signalling pathways of nitric oxide/ANP/guanylyl cyclases/cGMP-dependent protein kinase and cAMP/Epac/adenylyl cyclases/cAMP-dependent protein kinase. Furthermore, diverse possible drugs activating these pathways are discussed. From these diverse mechanisms it is expected that new pharmacological treatments will evolve for the therapy or even prevention of kidney failure.

  13. Dental Fusion with Oral Submucous Fibrosis

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    Ramachandran Sudarshan

    2013-04-01

    Full Text Available Dental Fusion is developmental anomaly due to the union of two tooth germs resulting in a single tooth. It is an infrequent phenomenon but may cause caries, periodontal, cosmetic and malocclusion abnormalities. Oral Submucous Fibrosis is a chronic inflammatory disorder and a precancerous condition affecting oral mucosa causing inability to open the mouth, burning sensation and leathery consistency. This manuscript describes a case of OSMF and dental fusion. [Cukurova Med J 2013; 38(2.000: 308-310

  14. The JNK Signaling Pathway in Renal Fibrosis

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    Keren Grynberg

    2017-10-01

    Full Text Available Fibrosis of the glomerular and tubulointerstitial compartments is a common feature of chronic kidney disease leading to end-stage renal failure. This fibrotic process involves a number of pathologic mechanisms, including cell death and inflammation. This review focuses on the role of the c-Jun amino terminal kinase (JNK signaling pathway in the development of renal fibrosis. The JNK pathway is activated in response to various cellular stresses and plays an important role in cell death and inflammation. Activation of JNK signaling is a common feature in most forms of human kidney injury, evident in both intrinsic glomerular and tubular cells as well as in infiltrating leukocytes. Similar patterns of JNK activation are evident in animal models of acute and chronic renal injury. Administration of JNK inhibitors can protect against acute kidney injury and suppress the development of glomerulosclerosis and tubulointerstitial fibrosis. In particular, JNK activation in tubular epithelial cells may be a pivotal mechanism in determining the outcome of both acute kidney injury and progression of chronic kidney disease. JNK signaling promotes tubular epithelial cell production of pro-inflammatory and pro-fibrotic molecules as well as tubular cell de-differentiation toward a mesenchymal phenotype. However, the role of JNK within renal fibroblasts is less well-characterized. The JNK pathway interacts with other pro-fibrotic pathways, most notable with the TGF-β/SMAD pathway. JNK activation can augment TGF-β gene transcription, induce expression of enzymes that activate the latent form of TGF-β, and JNK directly phosphorylates SMAD3 to enhance transcription of pro-fibrotic molecules. In conclusion, JNK signaling plays an integral role in several key mechanisms operating in renal fibrosis. Targeting of JNK enzymes has therapeutic potential for the treatment of fibrotic kidney diseases.

  15. Nephrogenic systemic fibrosis: history and epidemiology

    DEFF Research Database (Denmark)

    Thomsen, Henrik S

    2009-01-01

    Nephrogenic systemic fibrosis (NSF) is a new disease; the first case was diagnosed in 1997. It took 9 years before an association between NSF and gadolinium-based contrast agents (Gd-CAs) was identified. Gadolinium has several advantages for use in relation to enhanced MRI, but it is also a toxic...... that the real number of patients who have NSF has not been accurately totaled; the disease seems to be underdiagnosed for various reasons....

  16. Malnutrition and hepatic fibrosis in murine schistosomiasis

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    Eridan M Coutinho

    2004-08-01

    Full Text Available In this paper, four different approaches attempting to reproduce the schistosomal liver fibrosis in undernourished mice are reported: shifting from a deficient to a balanced diet and vice-versa, repeated infections, influence of the genetic background, and immunological response. Infections were performed with 30 cercariae of Schistosoma mansoni and lasted at least four months. Undernourished mice were unable to reproduce the picture of "pipestem" fibrosis, except the C57 BL/10 inbred strain, four out of 21 mice developing the liver lesion. A link of this histological finding to the type of parasite strain can not be discarded at the moment. Repeated infections increased collagen deposition mainly in well nourished animals (seven out of 16 Swiss mice developed "pipestem"-like fibrosis. In undernourished infected Swiss mice the serum levels of soluble egg antigen specific antibodies IgG1, IgG2a, IgG2b, and IgG3 were two to four times lower than those detected for well nourished controls. The decreased humoral immune response coupled to the morphological, morphometric, and biochemical results reinforce the influence of the host nutritional status on the connective tissue changes of hepatic schistosomiasis.

  17. Cystic fibrosis: a mucosal immunodeficiency syndrome

    Science.gov (United States)

    Cohen, Taylor Sitarik; Prince, Alice

    2013-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) functions as a channel that regulates the transport of ions and the movement of water across the epithelial barrier. Mutations in CFTR, which form the basis for the clinical manifestations of cystic fibrosis, affect the epithelial innate immune function in the lung, resulting in exaggerated and ineffective airway inflammation that fails to eradicate pulmonary pathogens. Compounding the effects of excessive neutrophil recruitment, the mutant CFTR channel does not transport antioxidants to counteract neutrophil-associated oxidative stress. Whereas mutant CFTR expression in leukocytes outside of the lung does not markedly impair their function, the expected regulation of inflammation in the airways is clearly deficient in cystic fibrosis. The resulting bacterial infections, which are caused by organisms that have substantial genetic and metabolic flexibility, can resist multiple classes of antibiotics and evade phagocytic clearance. The development of animal models that approximate the human pulmonary phenotypes—airway inflammation and spontaneous infection—may provide the much-needed tools to establish how CFTR regulates mucosal immunity and to test directly the effect of pharmacologic potentiation and correction of mutant CFTR function on bacterial clearance. PMID:22481418

  18. Mesenchymal stem cell therapy for liver fibrosis.

    Science.gov (United States)

    Eom, Young Woo; Shim, Kwang Yong; Baik, Soon Koo

    2015-09-01

    Currently, the most effective treatment for end-stage liver fibrosis is liver transplantation; however, transplantation is limited by a shortage of donor organs, surgical complications, immunological rejection, and high medical costs. Recently, mesenchymal stem cell (MSC) therapy has been suggested as an effective alternate approach for the treatment of hepatic diseases. MSCs have the potential to differentiate into hepatocytes, and therapeutic value exists in their immune-modulatory properties and secretion of trophic factors, such as growth factors and cytokines. In addition, MSCs can suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, regress liver fibrosis and enhance liver functionality. Despite these advantages, issues remain; MSCs also have fibrogenic potential and the capacity to promote tumor cell growth and oncogenicity. This paper summarizes the properties of MSCs for regenerative medicine and their therapeutic mechanisms and clinical application in the treatment of liver fibrosis. We also present several outstanding risks, including their fibrogenic potential and their capacity to promote pre-existing tumor cell growth and oncogenicity.

  19. Eosinophilic Angiocentric Fibrosis of the Nasal Septum

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    Yunchuan Li

    2013-01-01

    Full Text Available Background. Eosinophilic angiocentric fibrosis (EAF is a rare benign condition of unknown aetiology that causes stenosis of the upper respiratory tract. It is most commonly found at the nasal septum and sinus mucosa causing mucosal thickening and nasal obstructive symptoms. The diagnosis is mainly based on characteristic histologic findings. Case Report. A 27-year-old young woman presented with a slow growing mass at her anterior nasal septum for over eight years. She complained of persistent nasal obstruction, epistaxis, sometimes diffused facial pain, and chronic headache. 3 years ago, the tumor was partially resected for ventilation and a nasal septum perforation was left. Imaging findings indicated soft-tissue thickening of the anterior part of septum and adjacent lateral nasal walls. Pathological examination showed numerous inflammatory cells infiltrates containing eosinophils, fibroinflammatory lesion with a whorled appearance fibrosis which typically surrounded vessels. A diagnosis of eosinophilic angiocentric fibrosis was made. All laboratory tests were unremarkable. Skin prick test was positive. The tumor-like lesion was totally resected. Conclusions. EAF is a rare benign and progressive disorder causing destruction. Combined with radiological imaging of EAF historical findings contribute to the diagnosis. It is important to prevent tumor from recurrence by total resection of the lesion.

  20. Radiologic findings of malignant retroperitoneal fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yu Jin; Lee, Hae Kyung; Kim, Hyung Hwan; Cha, Jang Gyu; Hong, Hyun Sook; Kwon, Gui Hyang; Choi, Deuk Lin [Soonchunhyang Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-11-01

    To evaluate the radiologic findings of malignant retroperitoneal fibrosis. Post-contrast CT (n=9) and urographic (n=7) findings of nine patients with malignant retroperitoneal fibrosis were retrospectively analyzed. Primary tumors were found to be advanced gastric cancer (n=6), early gastric cancer (n=1), breast cancer (n=1), and cervical cancer (n=1). We analyzed CT findings with regard to the site of soft tissue lesion, ureteral involvement, the presence or absence of hydronephrosis, and distant metastasis. The level and length of ureteral involvement, presence or absence of ureteral stenosis, and ureteral displacement as seen on urography, were analyzed. On CT scans, enhanced soft tissue lesions (mass, 5 cases ; plaque, 4 cases) encircling the abdominal aorta and IVC were noted in all cases. Thickening of the ureteral wall (n=8), hydronephrosis (n=9), and enlarged lymph node (n=5) were also seen. On urography, irregular stenosis and medial displacement of ureters from level L2 to S2 were noted in all cases. The length of ureteral involvement was 4 - 6.5cm. The common CT findings of malignant retroperitoneal fibrosis were enhanced soft tissue lesion encircling the abdominal aorta and IVC, hydronephrosis, and thickening of the ureteral wall. On urography, ureteral stenosis and medial displacement were seen.

  1. Age and sex dimorphisms contribute to the severity of bleomycin-induced lung injury and fibrosis

    Science.gov (United States)

    Redente, Elizabeth F.; Jacobsen, Kristen M.; Solomon, Joshua J.; Lara, Abigail R.; Faubel, Sarah; Keith, Rebecca C.; Henson, Peter M.; Downey, Gregory P.

    2011-01-01

    Fibrotic interstitial pneumonias are more prevalent in males of advancing age, although little is known about the underlying mechanisms. To evaluate the contributions of age and sex to the development of pulmonary fibrosis, we intratracheally instilled young (8–12 wk) and aged (52–54 wk) male and female mice with bleomycin and assessed the development and severity of fibrotic lung disease by measurements of lung collagen levels, static compliance, leukocyte infiltration, and stereological quantification of fibrotic areas in histological sections. We also quantified proinflammatory and profibrotic chemokine and cytokine levels in the bronchoalveolar lavage fluid. Aged male mice developed more severe lung disease, indicated by increased mortality, increased collagen deposition, and neutrophilic alveolitis compared with aged female mice or young mice of either sex. Aged male mice also exhibited increased levels of transforming growth factor-β, IL-17A, and CXCL1 in their bronchoalveolar lavage fluid. Young male mice developed a more fibrotic disease after bleomycin instillation compared with female mice, regardless of age. There was no difference in fibrosis between young and aged female mice. Taken together, these findings suggest that the variables of advanced age and male sex contribute to the severity of pulmonary fibrosis in this model. Our findings also emphasize the importance of stratifying experimental groups on the basis of age and sex in experimental and epidemiological studies of this nature. PMID:21743030

  2. Pregnancy and cystic fibrosis: Approach to contemporary management

    Science.gov (United States)

    Tay, George; Callaway, Leonie; Bell, Scott C

    2014-01-01

    Over the previous 50 years survival of patients with cystic fibrosis has progressively increased. As a result of improvements in health care, increasing numbers of patients with cystic fibrosis are now considering starting families of their own. For the health care professionals who look after these patients, the assessment of the potential risks, and the process of guiding prospective parents through pregnancy and beyond can be both challenging and rewarding. To facilitate appropriate discussions about pregnancy, health care workers must have a detailed understanding of the various important issues that will ultimately need to be considered for any patient with cystic fibrosis considering parenthood. This review will address these issues. In particular, it will outline pregnancy outcomes for mothers with cystic fibrosis, issues that need to be taken into account when planning a pregnancy and the management of pregnancy for mothers with cystic fibrosis or mothers who have undergone organ transplantation as a result of cystic fibrosis. PMID:27512443

  3. Cardiac Remodelling and Fibrosis in Cardiomyopathy: Role of Galectin-3

    OpenAIRE

    MY-NHAN NGUYEN

    2018-01-01

    This thesis provides a comprehensive investigation on the contribution of heart scarring, known as cardiac fibrosis, to remodelling and impaired function of the heart. It highlights a relationship between the presence of cardiac fibrosis and severity of irregular heartbeats, and demonstrated the complex role of a molecule called ‘galectin-3’ in the pathogenesis of fibrosis and remodelling in cardiomyopathy. The thesis provides new mechanisms for elevation of galectin-3 blood levels that is in...

  4. Optical biopsy of liver fibrosis by use of multiphoton microscopy

    Science.gov (United States)

    Lee, Hsuan-Shu; Liu, Yuan; Chen, Hsiao-Ching; Chiou, Ling-Ling; Huang, Guan-Tarn; Lo, Wen; Dong, Chen-Yuan

    2004-11-01

    We demonstrate the application of multiphoton microscopy in diagnosing toxin- CCl4 - induced liver fibrosis in mice. Although hepatocyte autofluorescence does not vary significantly, different degrees of necrosis and stellate cell proliferation at necrotic sites in livers with fibrosis (ex vivo) can be detected easily from multiphoton-induced autofluorescence images by use of 780-nm excitation. Our result suggests that multiphoton microscopy can be developed into an effective technique for the detection and diagnosis of liver fibrosis in vivo.

  5. Association of cardiotrophin-1 with myocardial fibrosis in hypertensive patients with heart failure.

    Science.gov (United States)

    López, Begoña; González, Arantxa; Querejeta, Ramón; Larman, Mariano; Rábago, Gregorio; Díez, Javier

    2014-03-01

    Cardiotrophin-1 has been shown to be profibrogenic in experimental models. The aim of this study was to analyze whether cardiotrophin-1 is associated with left ventricular end-diastolic stress and myocardial fibrosis in hypertensive patients with heart failure. Endomyocardial biopsies from patients (n=31) and necropsies from 7 control subjects were studied. Myocardial cardiotrophin-1 protein and mRNA and the fraction of myocardial volume occupied by collagen were increased in patients compared with controls (Phypertensive patients with heart failure. It is proposed that exaggerated cardiomyocyte production of cardiotrophin-1 in response to increased left ventricular end-diastolic stress may contribute to fibrosis through stimulation of fibroblasts in heart failure of hypertensive origin.

  6. Dalbergioidin Ameliorates Doxorubicin-Induced Renal Fibrosis by Suppressing the TGF-β Signal Pathway

    Directory of Open Access Journals (Sweden)

    Xianguo Ren

    2016-01-01

    Full Text Available We investigated the effect of Dalbergioidin (DAL, a well-known natural product extracted from Uraria crinita, on doxorubicin- (DXR- induced renal fibrosis in mice. The mice were pretreated for 7 days with DAL followed by a single injection of DXR (10 mg/kg via the tail vein. Renal function was analyzed 5 weeks after DXR treatment. DXR caused nephrotoxicity. The symptoms of nephrotic syndrome were greatly improved after DAL treatment. The indices of renal fibrosis, the phosphorylation of Smad3, and the expression of alpha-smooth muscle actin (α-SMA, fibronectin, collagen III (Col III, E-cadherin, TGF-β, and Smad7 in response to DXR were all similarly modified by DAL. The present findings suggest that DAL improved the markers for kidney damage investigated in this model of DXR-induced experimental nephrotoxicity.

  7. Inhibition of the Unfolded Protein Response Mechanism Prevents Cardiac Fibrosis.

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    Jody Groenendyk

    Full Text Available Cardiac fibrosis attributed to excessive deposition of extracellular matrix proteins is a major cause of heart failure and death. Cardiac fibrosis is extremely difficult and challenging to treat in a clinical setting due to lack of understanding of molecular mechanisms leading to cardiac fibrosis and effective anti-fibrotic therapies. The objective in this study was to examine whether unfolded protein response (UPR pathway mediates cardiac fibrosis and whether a pharmacological intervention to modulate UPR can prevent cardiac fibrosis and preserve heart function.We demonstrate here that the mechanism leading to development of fibrosis in a mouse with increased expression of calreticulin, a model of heart failure, stems from impairment of endoplasmic reticulum (ER homeostasis, transient activation of the unfolded protein response (UPR pathway and stimulation of the TGFβ1/Smad2/3 signaling pathway. Remarkably, sustained pharmacologic inhibition of the UPR pathway by tauroursodeoxycholic acid (TUDCA is sufficient to prevent cardiac fibrosis, and improved exercise tolerance.We show that the mechanism leading to development of fibrosis in a mouse model of heart failure stems from transient activation of UPR pathway leading to persistent remodelling of cardiac tissue. Blocking the activation of the transiently activated UPR pathway by TUDCA prevented cardiac fibrosis, and improved prognosis. These findings offer a window for additional interventions that can preserve heart function.

  8. Fibrosis in nonalcoholic Fatty liver disease: mechanisms and clinical implications.

    Science.gov (United States)

    Angulo, Paul; Machado, Mariana Verdelho; Diehl, Anna Mae

    2015-05-01

    Nonalcoholic fatty liver disease (NAFLD) is tightly associated with obesity and the metabolic syndrome in the United States and other Western countries. It is also the liver disease most rapidly increasing in prevalence in the United States, and has become a major indication for liver transplantation worldwide. Compelling evidence shows that the degree of liver fibrosis dictates liver prognosis in NAFLD. This review focuses on fibrosis based on clinical and basic perspectives. The authors summarize the physiopathology of fibrosis development and progression in NAFLD, highlighting its molecular mechanisms, clinical consequences of fibrosis, the diagnostic approach and management strategies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. Idiopathic pulmonary fibrosis in a Staffordshire bull terrier with hypothyroidism.

    Science.gov (United States)

    Corcoran, B M; Dukes-McEwan, J; Rhind, S; French, A

    1999-04-01

    Radiographic evidence of chronic interstitial lung changes, usually believed to be attributable to lung fibrosis, is readily recognised in canine practice. Furthermore, there is a body of anecdotal evidence suggesting that a specific clinical entity consistent with chronic lung fibrosis occurs in specific breeds of terrier dogs. However, there is little pathological data to confirm these radiographic and clinical findings and, therefore, chronic interstitial lung disease of dogs is poorly characterised. In this report, a case of chronic pulmonary fibrosis is described in which histopathological confirmation was possible, and suggested that the condition might be analogous to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in humans.

  10. Oral calorie supplements for cystic fibrosis.

    Science.gov (United States)

    Smyth, Rosalind L; Rayner, Oli

    2017-05-04

    Poor nutrition occurs frequently in people with cystic fibrosis and is associated with other adverse outcomes. Oral calorie supplements are used to increase total daily calorie intake and improve weight gain. However, they are expensive and there are concerns they may reduce the amount of food eaten and not improve overall energy intake. This is an update of a previously published review. To establish whether in people with cystic fibrosis, oral calorie supplements: increase daily calorie intake; and improve overall nutritional intake, nutritional indices, lung function, survival and quality of life. To assess adverse effects associated with using these supplements. We searched the Cochrane Cystic Fibrosis Trials Register comprising references from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We contacted companies marketing oral calorie supplements.Last search: 18 October 2016. Randomised or quasi-randomised controlled trials comparing use of oral calorie supplements for at least one month to increase calorie intake with no specific intervention or additional nutritional advice in people with cystic fibrosis. We independently selected the included trials, assessed risk of bias and extracted data. We contacted the authors of included trials and obtained additional information for two trials. We identified 21 trials and included three, reporting results from 131 participants lasting between three months and one year. Two trials compared supplements to additional nutritional advice and one to no intervention. Two of the included trials recruited only children. In one trial the risk of bias was low across all domains, in a second trial the risk of bias was largely unclear and in the third mainly low. Blinding of participants was unclear in two of the trials. Also, in one trial the clinical condition of groups appeared to be unevenly balanced at baseline and in another trial there were

  11. Lysyl oxidase activity contributes to collagen stabilization during liver fibrosis progression and limits spontaneous fibrosis reversal in mice.

    Science.gov (United States)

    Liu, Susan B; Ikenaga, Naoki; Peng, Zhen-Wei; Sverdlov, Deanna Y; Greenstein, Andrew; Smith, Victoria; Schuppan, Detlef; Popov, Yury

    2016-04-01

    Collagen stabilization through irreversible cross-linking is thought to promote hepatic fibrosis progression and limit its reversibility. However, the mechanism of this process remains poorly defined. We studied the functional contribution of lysyl oxidase (LOX) to collagen stabilization and hepatic fibrosis progression/reversalin vivousing chronic administration of irreversible LOX inhibitor β-aminopropionitrile (BAPN, or vehicle as control) in C57Bl/6J mice with carbon tetrachloride (CCl4)-induced fibrosis. Fibrotic matrix stability was directly assessed using a stepwise collagen extraction assay and fibrotic septae morphometry. Liver cells and fibrosis were studied by histologic, biochemical methods and quantitative real-time reverse-transcription PCR. During fibrosis progression, BAPN administration suppressed accumulation of cross-linked collagens, and fibrotic septae showed widening and collagen fibrils splitting, reminiscent of remodeling signs observed during fibrosis reversal. LOX inhibition attenuated hepatic stellate cell activation markers and promoted F4/80-positive scar-associated macrophage infiltration without an increase in liver injury. In reversal experiments, BAPN-treated fibrotic mice demonstrated accelerated fibrosis reversal after CCl4withdrawal. Our findings demonstrate for the first time that LOX contributes significantly to collagen stabilization in liver fibrosis, promotes fibrogenic activation of attenuated hepatic stellate cells, and limits fibrosis reversal. Our data support the concept of pharmacologic targeting of LOX pathway to inhibit liver fibrosis and promote its resolution.-Liu, S. B., Ikenaga, N., Peng, Z.-W., Sverdlov, D. Y., Greenstein, A., Smith, V., Schuppan, D., Popov, Y. Lysyl oxidase activity contributes to collagen stabilization during liver fibrosis progression and limits spontaneous fibrosis reversal in mice. © FASEB.

  12. Mueller matrix microscope: a quantitative tool to facilitate detections and fibrosis scorings of liver cirrhosis and cancer tissues

    Science.gov (United States)

    Wang, Ye; He, Honghui; Chang, Jintao; He, Chao; Liu, Shaoxiong; Li, Migao; Zeng, Nan; Wu, Jian; Ma, Hui

    2016-07-01

    Today the increasing cancer incidence rate is becoming one of the biggest threats to human health. Among all types of cancers, liver cancer ranks in the top five in both frequency and mortality rate all over the world. During the development of liver cancer, fibrosis often evolves as part of a healing process in response to liver damage, resulting in cirrhosis of liver tissues. In a previous study, we applied the Mueller matrix microscope to pathological liver tissue samples and found that both the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters are closely related to the fibrous microstructures. In this paper, we take this one step further to quantitatively facilitate the fibrosis detections and scorings of pathological liver tissue samples in different stages from cirrhosis to cancer using the Mueller matrix microscope. The experimental results of MMPD and MMT parameters for the fibrotic liver tissue samples in different stages are measured and analyzed. We also conduct Monte Carlo simulations based on the sphere birefringence model to examine in detail the influence of structural changes in different fibrosis stages on the imaging parameters. Both the experimental and simulated results indicate that the polarized light microscope and transformed Mueller matrix parameters can provide additional quantitative information helpful for fibrosis detections and scorings of liver cirrhosis and cancers. Therefore, the polarized light microscope and transformed Mueller matrix parameters have a good application prospect in liver cancer diagnosis.

  13. Vitamin D supplementation for cystic fibrosis.

    Science.gov (United States)

    Ferguson, Janet H; Chang, Anne B

    2014-05-14

    Cystic fibrosis (CF) is a genetic disorder with multiorgan effects. In a subgroup with pancreatic insufficiency malabsorption of the fat soluble vitamins (A, D, E, K) may occur. Vitamin D is involved in calcium homeostasis and bone mineralisation and may have extraskeletal effects. This review examines the evidence for vitamin D supplementation in cystic fibrosis. To assess the effects of vitamin D supplementation on the frequency of vitamin D deficiency, respiratory outcomes and vitamin D toxicity in the cystic fibrosis population. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 08 July 2013. Randomised and quasi-randomised controlled studies of vitamin D supplementation compared to placebo in the cystic fibrosis population regardless of exocrine pancreatic function. Both authors independently assessed the risk of bias of each included study and extracted outcome data (from published study information) for assessment of bone mineralization, growth and nutritional status, frequency of vitamin D deficiency, respiratory status, quality of life and adverse events. Six studies (239 participants) are included, although only three studies provided data from 69 adults and children with cystic fibrosis for analysis. One study compared a single high dose of vitamin D (250,000 IU) to placebo at the time of hospital admission with a respiratory exacerbation in 30 pancreatic insufficient adults with cystic fibrosis. The second study compared supplemental 800 international units (IU) vitamin D and placebo for 12 months in 30 osteopenic pancreatic insufficient adults; both groups continued 900 IU vitamin D daily. The third study compared supplemental 1 g calcium alone, 1600 IU vitamin D alone, 1600 IU vitamin D and 1 g calcium and placebo in a double

  14. Anestesia peridural com lidocaína isolada ou associada à clonidina: efeito cardiorrespiratório e analgésico em cães Epidural anesthesia with lidocaine alone or combinated with clonidine: cardiopulmonary and analgesic effects in dogs

    Directory of Open Access Journals (Sweden)

    Renata Navarro Cassu

    2010-10-01

    Full Text Available Analgesia satisfatória tem sido relatada com a administração peridural de agonistas adrenérgicos em associação aos anestésicos locais. Objetivou-se, com este trabalho, avaliar o efeito analgésico e cardiorrespiratório da lidocaína isolada ou associada à clonidina via peridural lombossacra em cães. Seis cães foram submetidos a dois tratamentos, com intervalo mínimo de 15 dias entre cada avaliação. No tratamento L, foi empregada lidocaína 2% com vasoconstrictor (5mg kg-1 e, no tratamento C, a clonidina (10µg kg-1 foi associada à lidocaína, de modo a perfazer um volume final de 0,25ml kg-1. Os animais foram tranquilizados com acepromazina (0,05mg kg-1 IV e mantidos sob anestesia com isofluorano em máscara facial durante a punção do espaço peridural. Foram mensuradas: frequência cardíaca (FC, parâmetros eletrocardiográficos (ECG, frequência respiratória (f, pressão arterial sistólica (PAS, gases sanguíneos, temperatura retal (T, duração e extensão do bloqueio anestésico. A estatística foi realizada com análise de variância, teste de Tukey e teste t pareado (PSatisfactory analgesia has been related with epidural 2 adrenoceptor agonists in combination with local anesthetics. The aim of this study was to compare the analgesic and cardiopulmonary effects of lidocaine or lidocaine-clonidine epidural injections in healthy dogs. Dogs were randomly assigned to two groups of six animals each. The L group received lidocaine (5mg kg-1 L and the C group lidocaine plus clonidine (10µg kg-1 C. Preanaesthetic medication was carried out with acepromazine (0.05mg kg-1 IV. Anaesthesia was induced and maintained with isoflurane by facial mask for epidural injection. Heart rate (HH, electrocardiography (ECG, respiratory rate (RR, systolic arterial blood pressure (SAP, rectal temperature (RT, blood gases, duration of anesthesia and sensitive block level were investigated. Statistical analysis was performed with ANOVA, Tukey test

  15. Current Strategies for Quantitating Fibrosis in Liver Biopsy

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2015-01-01

    Full Text Available Objective: The present mini-review updated the progress in methodologies based on using liver biopsy. Data Sources: Articles for study of liver fibrosis, liver biopsy or fibrosis assessment published on high impact peer review journals from 1980 to 2014. Study Selection: Key articles were selected mainly according to their levels of relevance to this topic and citations. Results: With the recently mounting progress in chronic liver disease therapeutics, comes by a pressing need for precise, accurate, and dynamic assessment of hepatic fibrosis and cirrhosis in individual patients. Histopathological information is recognized as the most valuable data for fibrosis assessment. Conventional histology categorical systems describe the changes of fibrosis patterns in liver tissue; but the simplified ordinal digits assigned by these systems cannot reflect the fibrosis dynamics with sufficient precision and reproducibility. Morphometric assessment by computer assist digital image analysis, such as collagen proportionate area (CPA, detects change of fibrosis amount in tissue section in a continuous variable, and has shown its independent diagnostic value for assessment of advanced or late-stage of fibrosis. Due to its evident sensitivity to sampling variances, morphometric measurement is feasible to be taken as a reliable statistical parameter for the study of a large cohort. Combining state-of-art imaging technology and fundamental principle in Tissue Engineering, structure-based quantitation was recently initiated with a novel proof-of-concept tool, qFibrosis. qFibrosis showed not only the superior performance to CPA in accurately and reproducibly differentiating adjacent stages of fibrosis, but also the possibility for facilitating analysis of fibrotic regression and cirrhosis sub-staging. Conclusions: With input from multidisciplinary innovation, liver biopsy assessment as a new "gold standard" is anticipated to substantially support the accelerated

  16. Co-morbidity of cystic fibrosis and celiac disease in Scandinavian cystic fibrosis patients

    DEFF Research Database (Denmark)

    Fluge, G; Olesen, Hanne Vebert; Gilljam, M

    2009-01-01

    BACKGROUND: The co-morbidity of cystic fibrosis (CF) and celiac disease (CD) has been reported sporadically since the 1960s. To our knowledge, this is the first time a systematic screening is performed in a large cohort of CF patients. METHODS: Transglutaminase-IgA (TGA), endomysium-IgA (EMA...

  17. Co-morbidity of cystic fibrosis and celiac disease in Scandinavian cystic fibrosis patients

    DEFF Research Database (Denmark)

    Fluge, Gjermund; Olesen, Hanne Vebert; Giljam, Marita

    2009-01-01

    Background: The co-morbidity of cystic fibrosis (CF) and celiac disease (CD) has been reported sporadically since the 1960s. To our knowledge, this is the first time a systematic screening is performed in a large cohort of CF patients. Methods: Transglutaminase-IgA (TGA), endomysium-IgA (EMA...

  18. Fibrosis of Two: Epithelial Cell-Fibroblast Interactions in Pulmonary Fibrosis

    Science.gov (United States)

    Sakai, Norihiko; Tager, Andrew M.

    2013-01-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive and ultimately fatal accumulation of fibroblasts and extracellular matrix in the lung that distorts its architecture and compromises its function. IPF is now thought to result from wound-healing processes that, although initiated to protect the host from injurious environmental stimuli, lead to pathological fibrosis due to these processes becoming aberrant or over-exuberant. Although the environmental stimuli that trigger IPF remain to be identified, recent evidence suggests that they initially injure the alveolar epithelium. Repetitive cycles of epithelial injury and resultant alveolar epithelial cell death provoke the migration, proliferation, activation and myofibroblast differentiation of fibroblasts, causing the accumulation of these cells and the extracellular matrix that they synthesize. In turn, these activated fibroblasts induce further alveolar epithelial cell injury and death, thereby creating a vicious cycle of pro-fibrotic epithelial cell-fibroblast interactions. Though other cell types certainly make important contributions, we focus here on the “pas de deux” (steps of two), or perhaps more appropriate to IPF pathogenesis, the “folie à deux” (madness of two) of epithelial cells and fibroblasts that drives the progression of pulmonary fibrosis. We describe the signaling molecules that mediate the interactions of these cell types in their “fibrosis of two”, including transforming growth factor-β, connective tissue growth factor, sonic hedgehog, prostaglandin E2, angiotensin II and reactive oxygen species. PMID:23499992

  19. Omega-3 fatty acids for cystic fibrosis.

    Science.gov (United States)

    Oliver, Colleen; Watson, Helen

    2016-01-05

    Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. This is an updated version of a previously published review. To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality and to identify any adverse events associated with supplementation. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Authors and persons interested in the subject of the review were contacted.Date of last search: 13 August 2013. Randomised controlled trials in people with cystic fibrosis comparing omega-3 fatty acid supplements with placebo. Two authors independently selected studies for inclusion, extracted data and assessed the risk of bias of the studies. The searches identified 15 studies; four studies with 91 participants (children and adults) were included; duration of studies ranged from six weeks to six months. Two studies were judged to be at low risk of bias based on adequate randomisation but this was unclear in the other two studies. Three of the studies adequately blinded patients, however, the risk of bias was unclear in all studies with regards to allocation concealment and selective reporting.Two studies compared omega-3 fatty acids to olive oil for six weeks. One study compared a liquid dietary supplement containing omega-3 fatty acids to one without for six months. One study compared omega-3 fatty acids and omega-6 fatty acids to a control (capsules with customised fatty acid blends) for three months. Only one short-term study (19 participants) comparing omega-3 to placebo reported a significant improvement in lung function and Shwachman score and a reduction in sputum volume in the omega-3 group. Another

  20. Machine-learning-based classification of real-time tissue elastography for hepatic fibrosis in patients with chronic hepatitis B.

    Science.gov (United States)

    Chen, Yang; Luo, Yan; Huang, Wei; Hu, Die; Zheng, Rong-Qin; Cong, Shu-Zhen; Meng, Fan-Kun; Yang, Hong; Lin, Hong-Jun; Sun, Yan; Wang, Xiu-Yan; Wu, Tao; Ren, Jie; Pei, Shu-Fang; Zheng, Ying; He, Yun; Hu, Yu; Yang, Na; Yan, Hongmei

    2017-10-01

    Hepatic fibrosis is a common middle stage of the pathological processes of chronic liver diseases. Clinical intervention during the early stages of hepatic fibrosis can slow the development of liver cirrhosis and reduce the risk of developing liver cancer. Performing a liver biopsy, the gold standard for viral liver disease management, has drawbacks such as invasiveness and a relatively high sampling error rate. Real-time tissue elastography (RTE), one of the most recently developed technologies, might be promising imaging technology because it is both noninvasive and provides accurate assessments of hepatic fibrosis. However, determining the stage of liver fibrosis from RTE images in a clinic is a challenging task. In this study, in contrast to the previous liver fibrosis index (LFI) method, which predicts the stage of diagnosis using RTE images and multiple regression analysis, we employed four classical classifiers (i.e., Support Vector Machine, Naïve Bayes, Random Forest and K-Nearest Neighbor) to build a decision-support system to improve the hepatitis B stage diagnosis performance. Eleven RTE image features were obtained from 513 subjects who underwent liver biopsies in this multicenter collaborative research. The experimental results showed that the adopted classifiers significantly outperformed the LFI method and that the Random Forest(RF) classifier provided the highest average accuracy among the four machine algorithms. This result suggests that sophisticated machine-learning methods can be powerful tools for evaluating the stage of hepatic fibrosis and show promise for clinical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Ruxolitinib. Bone marrow fibrosis: theory versus practice.

    Science.gov (United States)

    2013-04-01

    Currently, the only curative treatment for bone marrow fibrosis is haematopoietic stem cell transplantation, but it is only feasible in a minority of patients. Ruxolitinib (Jakavi, Novartis) inhibits Janus kinases, enzymes necessary for haematopoiesis. Many cases of bone marrow fibrosis appear to be due to mutations that interfere with the expression of these kinases. Clinical assessment of ruxolitinib is based on a randomised placebo-controlled trial in 309 patients in whom conventional treatments had failed, and on a randomised, unblinded trial versus standard management in 219 patients. The patients enrolled in the placebo-controlled trial had a poor prognosis. Mortality appeared to be lower in the ruxolitinib arm after 24 and 51 weeks, but not in the trial versus standard management. Ruxolitinib had a short-lived symptomatic effect, but almost all patients enrolled in a non-comparative study discontinued ruxolitinib because of inadequate efficacy or adverse effects. Discontinuation often led to symptom rebound. The primary endpoint in these trials was the reduction in spleen volume, a surrogate outcome measure. Ruxolitinib was effective on this endpoint, but it is unclear whether reduction in spleen volume correlates with symptoms. Ruxolitinib aggravates haematological disorders associated with bone marrow fibrosis (anaemia, thrombocytopenia) and also causes neurological disorders (headache, dizziness, confusion). In practice, ruxolitinib appears to have an unfavourable harm-benefit balance in most patients. It is therefore better to avoid using this drug. Additional clinical trials are needed in patients for whom haematopoietic stem cell transplantation is not feasible, especially those with a large, expanding spleen.

  2. Liver Fibrosis and Altered Matrix Synthesis

    Directory of Open Access Journals (Sweden)

    Katrin Neubauer

    2001-01-01

    Full Text Available Liver fibrosis represents the uniform response of liver to toxic, infectious or metabolic agents. The process leading to liver fibrosis resembles the process of wound healing, including the three phases following tissue injury: inflammation, synthesis of collagenous and noncollagenous extracellular matrix components, and tissue remodelling (scar formation. While a single liver tissue injury can be followed by an almost complete restitution ad integrum, the persistence of the original damaging noxa results in tissue damage. During the establishment of liver fibrosis, the basement membrane components collagen type IV, entactin and laminin increase and form a basement membrane-like structure within the space of Disse. The number of endothelial fenestrae of the sinusoids decreases. These changes of the sinusoids are called 'capillarization' because the altered structure of the sinusoids resembles that of capillaries. At the cellular level, origin of liver fibrogenesis is initiated by the damage of hepatocytes, resulting in the recruitment of inflammatory cells and platelets, and activation of Kupffer cells, with subsequent release of cytokines and growth factors. The hepatic stellate cells seem to be the primary target cells for these inflammatory stimuli, because during fibrogenesis, they undergo an activation process to a myofibroblast-like cell, which represents the major matrix-producing cell. Based on this pathophysiological mechanism, therapeutic methods are developed to inhibit matrix synthesis or stimulate matrix degradation. A number of substances are currently being tested that either neutralize fibrogenic stimuli and prevent the activation of hepatic stellate cells, or directly modulate the matrix metabolism. However, until now, the elimination of the hepatotoxins has been the sole therapeutic concept available for the treatment of liver fibrogenesis in humans.

  3. Microbiological surveillance in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Paola Gualdi

    2010-06-01

    Full Text Available Pulmonary infections in patients with cystic fibrosis (CF, are a major cause of morbidity and mortality. Prevention, diagnosis and therapy in cystic fibrosis, lead to the necessary collaboration between clinical and laboratory to identify effective strategies and appropriate solutions to address the problems inherent isolation micro-organisms, antibiotic strategies, overcoming of bacterial resistance and other problems management of these patients. The task of the microbiology laboratory and research in quickly and accurately, the agents responsible for these infectious processes, in order to isolate them from material, identify and determine their sensitivity antibiotics. A microbiological surveillance on 34 patients (13 males and 21 females with CF and related to the “Support Services Provincial Trento for the treatment of cystic fibrosis “in the period July 2005 - August 2008, was carried out. 180 Gram positive and 278 of Gram negative bacteria as well as 235 fungi wre collected. Staphylococcus aureus was the most frequently organism found in patients with CF with an incidence of 23% on 156 strains isolated, Pseudomonas aeruginosa was collected 19% of all microorganisms isolated corresponding to 131 strains, Candida albicans is the yeast often isolated with a frequency 22% equal to 149 isolates, Aspergillus fumigatus was isolated at a rate of 8%. From the data we collected and processed has been noted that the local epidemiology of CF patients reflects as reported in the scientific literature and national international consulting, both as a type microorganisms that frequency also isolated compared to age groups. Considering the score of Bartlett as discriminating respiratory fitness of the material, it has been observed that only 32 samples over 327 total (10% would materials insignificant. It follows therefore that the time of sample collection, followed by personnel (physiotherapists dedicated to CF patients, represents a crucial step

  4. Cystic Fibrosis Revisited - a Review Study.

    Science.gov (United States)

    Klimova, Blanka; Kuca, Kamil; Novotny, Michal; Maresova, Petra

    2017-01-01

    Cystic fibrosis (CF) is an incurable, chronic disease, which causes severe damages to respiratory and digestive tracts. It is the most common genetically inherited disease among caucasians. This disease is caused by defects in CF genes, the so-called mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene population. At present over 100,000 people suffer from this disease worldwide. The purpose of this review study is to describe the pathophysiology of CF and provide the latest information on its diagnosis and treatment therapies with respect to the improvement of patient's quality of life and emphasis on targeted specialized care. The methodological approaches include a method of literature review of available sources exploring the issue of cystic fibrosis both from a global and specific perspective point of view. A search was performed in the databases PubMed, MEDLINE, Web of Science, Scopus, Springer and ScienceDirect. Furthermore, other sources cited in the analyzed studies were also examined. On the basis of evaluation of these literature sources, the research issue was explored. The main benefits (e.g., specialized centres for the treatment of CF exist or a new breakthrough in the gene therapy of CF has been made) and limitations (e.g., comorbidity of CF, lifelong and costly treatment, or adverse impact on patient's and caregiver's quality of life) in the treatment of narcolepsy are highlighted. CF requires an integrated treatment approach in specialized CF centers, involving various factors contributing to a better patient's state of health in the form of relevant and well-balanced non-pharmacological and pharmacological therapies. In addition, further large scale clinical trials are needed in order to develop compounds that are aimed at the most common classes of CFTR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. The lived experience with idiopathic pulmonary fibrosis

    DEFF Research Database (Denmark)

    Overgaard, Dorthe; Kaldan, Gudrun; Marsaa, Kristoffer

    2016-01-01

    The disease course in idiopathic pulmonary fibrosis (IPF) is variable, but patients experience a progressive decline in lung function and increased symptom burden leading to death. Little is known about the patients' experience and their needs during the disease course or about the burden on family......, emotional ambivalence, gradual and tacit role shift, and adapted coping strategies.Our findings suggest that IPF patients need information at the time of diagnosis, but some issues should be paced as the disease progresses. A palliation plan was demanded by patients and their caregivers. Further efforts...

  6. CYSTIC FIBROSIS: MICROBIOLOGY AND HOST RESPONSE

    Science.gov (United States)

    Zemanick, Edith T.

    2016-01-01

    THE EARLIEST DESCRIPTIONS OF LUNG DISEASE IN PEOPLE WITH CYSTIC FIBROSIS (CF) DEMONSTRATED THE INVOLVEMENT OF THREE INTERACTING PATHOPHYSIOLOGICAL ELEMENTS IN CF AIRWAYS: MUCUS OBSTRUCTION, INFLAMMATION, AND INFECTION. OVER THE PAST 7 DECADES, OUR UNDERSTANDING OF CF RESPIRATORY MICROBIOLOGY AND INFLAMMATION HAS EVOLVED WITH THE INTRODUCTION OF NEW TREATMENTS, WITH INCREASED LONGEVITY, AND WITH INCREASINGLY SOPHISTICATED LABORATORY TECHNIQUES. IN THIS CHAPTER, WE WILL REVIEW THE CURRENT STATE OF UNDERSTANDING OF THE ROLES OF INFECTION AND INFLAMMATION AND THEIR ROLES IN DRIVING LUNG DISEASE. WE WILL ALSO DISCUSS HOW THIS CONSTANTLY EVOLVING INFORMATION IS USED TO INFORM CURRENT THERAPEUTIC STRATEGIES, MEASURES AND PREDICTORS OF DISEASE SEVERITY, AND RESEARCH PRIORITIES. PMID:27469179

  7. Respiratory bacterial infections in cystic fibrosis

    DEFF Research Database (Denmark)

    Ciofu, Oana; Hansen, Christine R; Høiby, Niels

    2013-01-01

    PURPOSE OF REVIEW: Bacterial respiratory infections are the main cause of morbidity and mortality in patients with cystic fibrosis (CF). Pseudomonas aeruginosa remains the main pathogen in adults, but other Gram-negative bacteria such as Achromobacter xylosoxidans and Stenotrophomonas maltophilia...... and site of bacterial adaptation has been recognized. This review will focus on the different conditions encountered by the bacteria in sinuses and lung, as well as the principles of treatment in the different infection sites. SUMMARY: Chronic, pulmonary infections remain the single most prominent cause...

  8. FIBROSIS PROGRESIVA DEL CUÁDRICEPS

    Directory of Open Access Journals (Sweden)

    Enrique Vergara Amador

    2011-04-01

    Discusión. El vasto intermedio ha sido utilizado para aplicación de medicamentos. Se tiene evidencia que esta porción muscular tiene una pobre perfusión sanguínea en niños. No se conoce aún exactamente la fisiopatología de la fibrosis. Muchos niños son mal diagnosticados, confundiéndolos con patologías articulares y reciben equivocadamente otros tipos de cirugías.

  9. Vitamin K supplementation for cystic fibrosis.

    Science.gov (United States)

    Jagannath, Vanitha A; Thaker, Vidhu; Chang, Anne B; Price, Amy I

    2017-08-22

    Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. This is an updated version of the review. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 30 January 2017. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Two trials (total of 32 participants) each lasting one month were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial in children (aged 8 to 18 years); and the other (with an older cohort) had a cross-over design comparing supplements to no treatment, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin

  10. Fibrosis: a structural modulator of Sinoatrial Node physiology and dysfunction

    Directory of Open Access Journals (Sweden)

    Thomas A Csepe

    2015-02-01

    Full Text Available Heart rhythm is initialized and controlled by the Sinoatrial Node (SAN, the primary pacemaker of the heart. The SAN is a heterogeneous multi-compartment structure characterized by clusters of specialized cardiomyocytes, enmeshed within strands of connective tissue or fibrosis. Intranodal fibrosis is emerging as an important modulator of structural and functional integrity of the SAN pacemaker complex. In adult human hearts, fatty tissue and fibrosis insulate the SAN from the hyperpolarizing effect of the surrounding atria while electrical communication between the SAN and right atrium is restricted to discrete SAN conduction pathways. The amount of fibrosis within the SAN is inversely correlated with heart rate, while age and heart size are positively correlated with fibrosis. Pathological upregulation of fibrosis within the SAN may lead to tachycardia-bradycardia arrhythmias and cardiac arrest, possibly due to SAN reentry and exit block, and is associated with atrial fibrillation, ventricular arrhythmias, heart failure and myocardial infarction. In this review, we will discuss current literature on the role of fibrosis in normal SAN structure and function, as well as the causes and consequences of SAN fibrosis upregulation in disease conditions.

  11. Non invasive assessment of liver fibrosis in chronic hemodialysis ...

    African Journals Online (AJOL)

    The liver biopsy has long been the "gold standard" for assessing liver fibrosis in patients with hepatitis C. It's an invasive procedure which is associated with an elevated bleeding, especially in chronic hemodialysis patients. Main goal is to assess liver fibrosis in chronic hemodialysis with HCV by Fibroscan and by biological ...

  12. Lung function in South African children with cystic fibrosis | Zar ...

    African Journals Online (AJOL)

    Lung function in South African children with cystic fibrosis. H J Zar, B Moore, A Argent, J Ireland, A T R Westwood. Abstract. Objective: To determine the pattern of lung function in stable cystic fibrosis (CF) patients and to investigate the relationship of abnormal lung function to demographic variables, CF genotype and ...

  13. Clinical presentation of exclusive cystic fibrosis lung disease

    NARCIS (Netherlands)

    I. Bronsveld (Inez); J. Bijman (Jan); F. Mekus; M. Ballmann; H.J. Veeze; B. Tummler

    1999-01-01

    textabstractThe diagnosis of cystic fibrosis (CF) is based on the occurrence of two mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and on assays that measure the basic defect of abnormal chloride transport in the affected organs.

  14. Computed Tomography in the Evaluation of Cystic Fibrosis Lung Disease

    National Research Council Canada - National Science Library

    Brody, Alan S; Tiddens, Harm A. W. M; Castile, Robert G; Coxson, Harvey O; de Jong, Pim A; Goldin, Jonathan; Huda, Walter; Long, Frederick R; McNitt-Gray, Michael; Rock, Michael; Robinson, Terry E; Sagel, Scott D; CT Scanning in Cystic Fibrosis Special Interest Group

    2005-01-01

    ... of this article is to present the current status of CT scanning in CF. Keywords: computed tomography X-ray; cystic fibrosis; radiation effects; research design The first report of computed tomography (CT) scanning to monitor cystic fibrosis (CF)-related lung disease was published in 1986 (1). Further publications followed, but in general there was little i...

  15. Acupuncture in Treating Hepatic Fibrosis: A Review with ...

    African Journals Online (AJOL)

    ... immunity, which are important factors in treating hepatic fibrosis. The aim of this review was to appraise the current limited evidence of acupuncture in treating hepatic fibrosis from both animal experiments and clinical trials by using both Chinese and western databases and to provide recommendations for future studies.

  16. Novel diagnostic and therapeutic opportunities for Cystic Fibrosis

    NARCIS (Netherlands)

    Vijftigschild, L.A.W.

    2016-01-01

    Cystic fibrosis (CF) is the most common life-shortening rare disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which was identified in 1989. The CFTR gene encodes a 3’,5’-cyclic adenosine monophosphate (cAMP)-activated transmembrane anion channel and

  17. Heart dysfunction and fibrosis in rat treated with myocardial ...

    African Journals Online (AJOL)

    use

    2011-11-16

    Nov 16, 2011 ... study was to establish the rat model animal and to compare the heart dysfunction and fibrosis with SD ..... Figure 4. The myocardial fibrosis formation after myocardial ischemia and reperfusion surgery. Pictures on the left were hematoxylin and eosin (H and E) staining results, pictures on the right were ...

  18. Biomarkers for liver fibrosis: Advances, advantages and disadvantages

    Directory of Open Access Journals (Sweden)

    A. Cequera

    2014-07-01

    In this paper, we describe the biomarkers that are currently being used for studying liver fibrosis in humans, their advantages and disadvantages, as well as the implementation of new-generation technologies and the evaluation of their possible use in the diagnosis of fibrosis.

  19. Fibrosis Assessment in Nonalcoholic Fatty Liver Disease (NAFLD) in 2016.

    Science.gov (United States)

    Kaswala, Dharmesh H; Lai, Michelle; Afdhal, Nezam H

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver pathologies characterized by hepatic steatosis with a history of little to no alcohol consumption or secondary causes of hepatic steatosis. The prevalence of NAFLD is 20-25 % of the general population in the Western countries and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. The spectrum of disease ranges from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis. Advanced fibrosis is the most significant predictor of mortality in NAFLD. It is crucial to assess for the presence and degree of hepatic fibrosis in order to make therapeutic decisions and predict clinical outcomes. Liver biopsy, the current gold standard to assess the liver fibrosis, has a number of drawbacks such as invasiveness, sampling error, cost, and inter-/intra-observer variability. There are currently available a number of noninvasive tests as an alternative to liver biopsy for fibrosis staging. These noninvasive fibrosis tests are increasingly used to rule out advanced fibrosis and help guide disease management. While these noninvasive tests perform relatively well for ruling out advanced fibrosis, they also have limitations. Understanding the strengths and limitations of liver biopsy and the noninvasive tests is necessary for deciding when to use the appropriate tests in the evaluation of patients with NAFLD.

  20. The Processes and Mechanisms of Cardiac and Pulmonary Fibrosis

    NARCIS (Netherlands)

    Murtha, Lucy A.; Schuliga, Michael J.; Mabotuwana, Nishani S.; Hardy, Sean A.; Waters, David W.; Burgess, Janette K.; Knight, Darryl A.; Boyle, Andrew J.

    2017-01-01

    Fibrosis is the formation of fibrous connective tissue in response to injury. It is characterized by the accumulation of extracellular matrix components, particularly collagen, at the site of injury. Fibrosis is an adaptive response that is a vital component of wound healing and tissue repair.

  1. Typing of Pseudomonas aeruginosa strains in Norwegian cystic fibrosis patients

    DEFF Research Database (Denmark)

    Fluge, G; Ojeniyi, B; Høiby, N

    2001-01-01

    OBJECTIVES: Typing of Pseudomonas aeruginosa isolates from Norwegian cystic fibrosis (CF) patients with chronic Pseudomonas lung infection in order to see whether cross-infection might have occurred. METHODS: Isolates from 60 patients were collected during the years 1994-98, and typed by pulsed...... between cystic fibrosis patients has occurred....

  2. Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats

    Directory of Open Access Journals (Sweden)

    Lili eGao

    2015-10-01

    Full Text Available Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present. Glycyrrhizic acid (GA, a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown. In this study, we investigated the potential therapeutic effect of GA on pulmonary fibrosis in a rat model with bleomycin (BLM-induced pulmonary fibrosis. The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition and activation of tansforming growth factor-beta signaling pathway in the lungs. Further, we demonstrated that GA treatment inhibited proliferation of 3T6 fibroblast cells, induced cell cycle arrest and promoted apoptosis in vitro, implying that GA-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. In summary, our study suggests a therapeutic potential of GA in the treatment of pulmonary fibrosis.

  3. Nephrogenic systemic fibrosis (NSF) and gadolinium-based contrast ...

    African Journals Online (AJOL)

    Nephrogenic systemic fibrosis (NSF), unknown before March 1997 and first described in 2000, is a systemic disorder characterised by widespread tissue fibrosis. The first known case occurred in 1997, after the use of gadolinium-based contrast agents (GBCAs) at high doses in patients with renal failure had become routine.

  4. Growth and nutrition in South African children with cystic fibrosis ...

    African Journals Online (AJOL)

    Growth and nutrition in South African children with cystic fibrosis. ... To study nutritional status and its dietary correlates in a South African cystic fibrosis (CF) population. Design. Cross-sectional survey. Population. ... of energy and fat. Greater attention needs to be given to overcoming malnutrition among older children.

  5. Imatinib in the treatment of nephrogenic systemic fibrosis.

    Science.gov (United States)

    Chandran, Sindhu; Petersen, Jeffrey; Jacobs, Charlotte; Fiorentino, David; Doeden, Katherine; Lafayette, Richard A

    2009-01-01

    Nephrogenic systemic fibrosis is a disabling progressive condition that is being reported with increased frequency in patients with kidney disease. Treatment is extremely limited and largely supportive. We report a case of severe nephrogenic systemic fibrosis in a dialysis patient exposed to multiple doses of gadolinium who improved clinically and histologically with treatment with imatinib.

  6. Cystic fibrosis with normal sweat chloride concentration: case report

    Directory of Open Access Journals (Sweden)

    Silva Filho Luiz Vicente Ferreira da

    2003-01-01

    Full Text Available Cystic fibrosis is a genetic disease usually diagnosed by abnormal sweat testing. We report a case of an 18-year-old female with bronchiectasis, chronic P. aeruginosa infection, and normal sweat chloride concentrations who experienced rapid decrease of lung function and clinical deterioration despite treatment. Given the high suspicion ofcystic fibrosis, broad genotyping testing was performed, showing a compound heterozygous with deltaF508 and 3849+10kb C->T mutations, therefore confirming cystic fibrosis diagnosis. Although the sweat chloride test remains the gold standard for the diagnosis of cystic fibrosis, alternative diagnostic tests such as genotyping and electrophysiologic measurements must be performed if there is suspicion of cystic fibrosis, despite normal or borderline sweat chloride levels.

  7. Normal sweat chloride test does not rule out cystic fibrosis.

    Science.gov (United States)

    Başaran, Abdurrahman Erdem; Karataş-Torun, Nimet; Maslak, İbrahim Cemal; Bingöl, Ayşen; Alper, Özgül M

    2017-01-01

    Başaran AE, Karataş-Torun N, Maslak İC, Bingöl A, Alper ÖM. Normal sweat chloride test does not rule out cystic fibrosis. Turk J Pediatr 2017; 59: 68-70. A 5-month-old patient presented with complaints of fever and cough. He was hospitalized with the diagnosis of bronchopneumonia and pseudo-Bartter's syndrome. Patient was further investigated for diagnosis of cystic fibrosis. The chloride (Cl) level in sweat was determined within the normal range (25.1 mmol/L, 20.3 mmol/L). CFTR (Cystic Fibrosis Transmembrane Regulator gene; NM_000492.2) genotyping results were positive for p.E92K; p.F1052V mutations. The patient was diagnosed with cystic fibrosis. In our patient, with features of CF and normal sweat test, mutation analysis was helpful for the diagnosis of cystic fibrosis.

  8. Myocardial fibrosis in patients with myotonic dystrophy type 1

    DEFF Research Database (Denmark)

    Petri, Helle; Ahtarovski, Kiril Aleksov; Vejlstrup, Niels

    2014-01-01

    , and the association between myocardial fibrosis and abnormal findings on ECG, Holter-monitoring and echocardiography. METHODS: We selected 30 unrelated patients with DM1: 18 patients (10 men, mean age 51 years) with, and 12 patients (7 men, mean age 41 years) without abnormal findings on ECG and Holter-monitoring....... Patients were evaluated with medical history, physical examination, ECG, Holter-monitoring, echocardiography and CMR. RESULTS: Myocardial fibrosis was found in 12/30 (40%, 9 men). The presence of myocardial fibrosis was associated with the following CMR-parameters: increased left ventricular mass (median...... of myocardial fibrosis and abnormal findings on: ECG (p = 0.71), Holter-monitoring (p = 0.27) or echocardiographic measurements of left ventricular volumes, ejection fraction or global longitudinal strain (p = 0.18). CONCLUSION: Patients with DM1 had a high prevalence of myocardial fibrosis which...

  9. Reversal of liver fibrosis: From fiction to reality.

    Science.gov (United States)

    Zoubek, Miguel Eugenio; Trautwein, Christian; Strnad, Pavel

    2017-04-01

    In chronic liver diseases, an ongoing hepatocellular injury together with inflammatory reaction results in activation of hepatic stellate cells (HSCs) and increased deposition of extracellular matrix (ECM) termed as liver fibrosis. It can progress to cirrhosis that is characterized by parenchymal and vascular architectural changes together with the presence of regenerative nodules. Even at late stage, liver fibrosis is reversible and the underlying mechanisms include a switch in the inflammatory environment, elimination or regression of activated HSCs and degradation of ECM. While animal models have been indispensable for our understanding of liver fibrosis, they possess several important limitations and need to be further refined. A better insight into the liver fibrogenesis resulted in a large number of clinical trials aiming at reversing liver fibrosis, particularly in patients with non-alcoholic steatohepatitis. Collectively, the current developments demonstrate that reversal of liver fibrosis is turning from fiction to reality. Copyright © 2017. Published by Elsevier Ltd.

  10. Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

    DEFF Research Database (Denmark)

    Johansen, H.K.; Gøtzsche, Peter C.; Johansen, Helle Krogh

    2008-01-01

    BACKGROUND: Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. OBJECTIVES......: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search May 2008) and PubMed using the terms vaccin* AND cystic...... fibrosis (last search May 2008). SELECTION CRITERIA: Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently selected trials...

  11. Could MRI Be Used To Image Kidney Fibrosis? A Review of Recent Advances and Remaining Barriers.

    Science.gov (United States)

    Leung, General; Kirpalani, Anish; Szeto, Stephen G; Deeb, Maya; Foltz, Warren; Simmons, Craig A; Yuen, Darren A

    2017-06-07

    A key contributor to the progression of nearly all forms of CKD is fibrosis, a largely irreversible process that drives further kidney injury. Despite its importance, clinicians currently have no means of noninvasively assessing renal scar, and thus have historically relied on percutaneous renal biopsy to assess fibrotic burden. Although helpful in the initial diagnostic assessment, renal biopsy remains an imperfect test for fibrosis measurement, limited not only by its invasiveness, but also, because of the small amounts of tissue analyzed, its susceptibility to sampling bias. These concerns have limited not only the prognostic utility of biopsy analysis and its ability to guide therapeutic decisions, but also the clinical translation of experimental antifibrotic agents. Recent advances in imaging technology have raised the exciting possibility of magnetic resonance imaging (MRI)-based renal scar analysis, by capitalizing on the differing physical features of fibrotic and nonfibrotic tissue. In this review, we describe two key fibrosis-induced pathologic changes (capillary loss and kidney stiffening) that can be imaged by MRI techniques, and the potential for these new MRI-based technologies to noninvasively image renal scar. Copyright © 2017 by the American Society of Nephrology.

  12. Interplay of Matrix Stiffness and c-SRC in Hepatic Fibrosis

    DEFF Research Database (Denmark)

    Görtzen, Jan; Schierwagen, Robert; Bierwolf, Jeanette

    2015-01-01

    . This study investigated the interaction of c-SRC and RhoA under different matrix stiffness conditions. METHODS: Liver fibrosis was induced in rats using bile duct ligation (BDL), thioacetamide (TAA) or carbon tetrachloride (CCl4) models. mRNA levels of albumin, PDGF-R, RHOA, COL1A1, and αSMA were analyzed....... RESULTS: Transcription of albumin and RhoA was decreased, whereas transcription and activation of c-SRC was increased in hepatocytes cultured on 12 kPa compared to 1 kPa gels. LX2 cells cultured on 12 kPa gels showed upregulation of RHOA, COL1A1, and αSMA mRNA levels. Inhibition of c-SRC by PP2 in LX2...... cells led to an increase in COL1A1 and αSMA most prominently in 12 kPa gels. In LX2 cells with RhoA overexpression, c-SRC inhibition by PP2 failed to improve fibrosis. RhoA expression was significantly elevated in human and experimental liver fibrosis, while c-SRC was inactivated. CONCLUSIONS...

  13. Pathogenesis pathways of idiopathic pulmonary fibrosis in bleomycin-induced lung injury model in mice.

    Science.gov (United States)

    Shi, Keyun; Jiang, Jianzhong; Ma, Tieliang; Xie, Jing; Duan, Lirong; Chen, Ruhua; Song, Ping; Yu, Zhixin; Liu, Chao; Zhu, Qin; Zheng, Jinxu

    2014-01-01

    Our objective was to investigate the pathogenesis pathways of idiopathic pulmonary fibrosis (IPF). Bleomycin (BLM) induced animal models of experimental lung fibrosis were used. CHIP assay was executed to find the link between Smad3 and IL-31, and the expressions of TGF-β1, Smad3, IL-31 and STAT1 were detected to find whether they were similar with each other. We found that in the early injury or inflammation of the animal model, BLM promoted the development of inflammation, leading to severe pulmonary fibrosis. Then the expression of TGF-β1 and Smad3 increased. Activated Smad3 bound to the IL-31 promoter region, followed by the activation of JAK-STAT pathways. The inhibitor of TGF-β1 receptor decreased the IL-31 expression and knocking-down of IL-31 also decreased the STAT1 expression. We conclude that there is a pathway of pathogenesis in BLM-induced mouse model that involves the TGF-β, IL-31 and JAKs/STATs pathway. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Streptococcus pneumoniae triggers progression of pulmonary fibrosis through pneumolysin.

    Science.gov (United States)

    Knippenberg, Sarah; Ueberberg, Bianca; Maus, Regina; Bohling, Jennifer; Ding, Nadine; Tort Tarres, Meritxell; Hoymann, Heinz-Gerd; Jonigk, Danny; Izykowski, Nicole; Paton, James C; Ogunniyi, Abiodun D; Lindig, Sandro; Bauer, Michael; Welte, Tobias; Seeger, Werner; Guenther, Andreas; Sisson, Thomas H; Gauldie, Jack; Kolb, Martin; Maus, Ulrich A

    2015-07-01

    Respiratory tract infections are common in patients suffering from pulmonary fibrosis. The interplay between bacterial infection and fibrosis is characterised poorly. To assess the effect of Gram-positive bacterial infection on fibrosis exacerbation in mice. Fibrosis progression in response to Streptococcus pneumoniae was examined in two different mouse models of pulmonary fibrosis. We demonstrate that wild-type mice exposed to adenoviral vector delivery of active transforming growth factor-β1 (TGFß1) or diphteria toxin (DT) treatment of transgenic mice expressing the DT receptor (DTR) under control of the surfactant protein C (SPC) promoter (SPC-DTR) to induce pulmonary fibrosis developed progressive fibrosis following infection with Spn, without exhibiting impaired lung protective immunity against Spn. Antibiotic treatment abolished infection-induced fibrosis progression. The cytotoxin pneumolysin (Ply) of Spn caused this phenomenon in a TLR4-independent manner, as Spn lacking Ply (SpnΔply) failed to trigger progressive fibrogenesis, whereas purified recombinant Ply did. Progressive fibrogenesis was also observed in AdTGFβ1-exposed Ply-challenged TLR4 KO mice. Increased apoptotic cell death of alveolar epithelial cells along with an attenuated intrapulmonary release of antifibrogenic prostaglandin E2 was found to underlie progressive fibrogenesis in Ply-challenged AdTGFβ1-exposed mice. Importantly, vaccination of mice with the non-cytotoxic Ply derivative B (PdB) substantially attenuated Ply-induced progression of lung fibrosis in AdTGFβ1-exposed mice. Our data unravel a novel mechanism by which infection with Spn through Ply release induces progression of established lung fibrosis, which can be attenuated by protein-based vaccination of mice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  15. Cystic fibrosis defects in intestinal bile acid and guanylin signaling : Signaal transductie door galzouten en guanylines in cystic fibrosis darmepitheel

    NARCIS (Netherlands)

    P.T. Ikpa (Pauline)

    2017-01-01

    markdownabstractCystic fibrosis (CF) is caused by dysfunction of the Cystic fibrosis transmembrane conductance regulator (CFTR) resulting in dehydration and acidification of the luminal surface of CFTR-expressing epithelia. Combined, these factors lead to accretion of viscous mucus and inspissation

  16. Fibroblasts in fibrosis: novel roles and mediators

    Directory of Open Access Journals (Sweden)

    Ryan Thomas Kendall

    2014-05-01

    Full Text Available Fibroblasts are the most common cell type of the connective tissues found throughout the body and the principal source of the extensive extracellular matrix (ECM characteristic of these tissues. They are also the central mediators of the pathological fibrotic accumulation of ECM and the cellular proliferation and differentiation that occurs in response to prolonged tissue injury and chronic inflammation. The transformation of the fibroblast cell lineage involves classical developmental signaling programs and includes a surprisingly diverse range of precursor cell types—most notably, myofibroblasts that are the apex of the fibrotic phenotype. Myofibroblasts display exaggerated ECM production; constitutively secrete and are hypersensitive to chemical signals such as cytokines, chemokines, and growth factors; and are endowed with a contractile apparatus allowing them to manipulate the ECM fibers physically to close open wounds. In addition to ECM production, fibroblasts have multiple concomitant biological roles, such as in wound healing, inflammation, and angiogenesis, which are each interwoven with the process of fibrosis. We now recognize many common fibroblast-related features across various physiological and pathological protracted processes. Indeed, a new appreciation has emerged for the role of noncancerous fibroblast interactions with tumors in cancer progression. Although the predominant current clinical treatments of fibrosis involve nonspecific immunosuppressive and anti-proliferative drugs, a variety of potential therapies under investigation specifically target fibroblast biology.

  17. Is nintedanib effective for idiopathic pulmonary fibrosis?

    Directory of Open Access Journals (Sweden)

    Alejandro Jeldres

    2017-06-01

    Full Text Available Resumen La fibrosis pulmonar idiopática es una enfermedad de mal pronóstico y cuyas terapias efectivas son escasas. En la búsqueda de tratamientos que puedan modificar el curso de la enfermedad ha surgido como una alternativa el nintedanib (BIBF 1120, un inhibidor de tirosina kinasa. Sin embargo, su rol aún no está claro. Para responder esta pregunta utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples fuentes de información. Identificamos siete revisiones sistemáticas que en conjunto incluyen siete estudios aleatorizados. Extrajimos los datos, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Concluimos que nintedanib probablemente disminuye el riesgo de exacerbaciones agudas, y podría reducir la mortalidad en la fibrosis pulmonar idiopática. Por otra parte, probablemente no se asocia a eventos adversos serios.

  18. New horizons for cystic fibrosis treatment.

    Science.gov (United States)

    Fajac, Isabelle; De Boeck, Kris

    2017-02-01

    Cystic fibrosis is an inherited multi-system disease associated with chronic lung infection, malabsorption, salt loss syndromes, male infertility and leading to numerous comorbidities. The landscape in cystic fibrosis care has changed markedly with currently more adult patients than children in many countries. Over 2000 different mutations in the CFTR gene have been reported and the majority are extremely rare. Understanding how CFTR mutations translate to disturbed synthesis or function of the CFTR protein has opened the way to 'personalized' treatments to correct the basic defect. The first 2 drugs have reached the clinic: a CFTR potentiator to augment CFTR channel function, and the combination of this potentiator with a corrector to increase CFTR expression at the cell membrane. To obtain robust correction of CFTR expression at the cell membrane, combinations of correctors with additive efficacy are under investigation. Other mutation type-specific treatments under clinical investigation are premature stop codon-read through drugs and antisense oligonucleotides that correct the basic defect at the mRNA level. Restoring the defective gene by gene editing can already be achieved ex vivo. Mutation agnostic treatments are explored as well: stabilizing CFTR expression at the cell membrane, circumventing the CFTR channel by blocking or activating other ion channels, and gene therapy. Combinations of these therapies can be anticipated. The pipeline of corrective strategies under clinical investigation is increasing continuously and a rising number of pharmaceutical companies are entering the field. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Cystic Fibrosis and the Nervous System.

    Science.gov (United States)

    Reznikov, Leah R

    2017-05-01

    Cystic fibrosis (CF) is a life-shortening autosomal recessive disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an anion channel that conducts bicarbonate and chloride across cell membranes. Although defective anion transport across epithelial cells is accepted as the basic defect in CF, many of the features observed in people with CF and organs affected by CF are modulated by the nervous system. This is of interest because CFTR expression has been reported in both the peripheral and central nervous systems, and it is well known that the transport of anions, such as chloride, greatly modulates neuronal excitability. Thus it is predicted that in CF, lack of CFTR in the nervous system affects neuronal function. Consistent with this prediction, several nervous system abnormalities and nervous system disorders have been described in people with CF and in animal models of CF. The goal of this special feature article is to highlight the expression and function of CFTR in the nervous system. Special emphasis is placed on nervous system abnormalities described in people with CF and in animal models of CF. Finally, features of CF that may be modulated by or attributed to faulty nervous system function are discussed. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  20. Cystic fibrosis chronic rhinosinusitis: A comprehensive review

    Science.gov (United States)

    Chaaban, Mohamad R.; Kejner, Alexandra; Rowe, Steven M.

    2013-01-01

    Background: Advances in the care of patients with cystic fibrosis (CF) have improved pulmonary outcomes and survival. In addition, rapid developments regarding the underlying genetic and molecular basis of the disease have led to numerous novel targets for treatment. However, clinical and basic scientific research focusing on therapeutic strategies for CF-associated chronic rhinosinusitis (CRS) lags behind the evidence-based approaches currently used for pulmonary disease. Methods: This review evaluates the available literature and provides an update concerning the pathophysiology, current treatment approaches, and future pharmaceutical tactics in the management of CRS in patients with CF. Results: Optimal medical and surgical strategies for CF CRS are lacking because of a dearth of well-performed clinical trials. Medical and surgical interventions are supported primarily by level 2 or 3 evidence and are aimed at improving clearance of mucus, infection, and inflammation. A number of novel therapeutics that target the basic defect in the cystic fibrosis transmembrane conductance regulator channel are currently under investigation. Ivacaftor, a corrector of the G551D mutation, was recently approved by the Food and Drug Administration. However, sinonasal outcomes using this and other novel drugs are pending. Conclusion: CRS is a lifelong disease in CF patients that can lead to substantial morbidity and decreased quality of life. A multidisciplinary approach will be necessary to develop consistent and evidence-based treatment paradigms. PMID:24119602

  1. Managing comorbidities in idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Fulton BG

    2015-09-01

    Full Text Available Blair G Fulton,1 Christopher J Ryerson1,2 1Department of Medicine, 2Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada Abstract: Major risk factors for idiopathic pulmonary fibrosis (IPF include older age and a history of smoking, which predispose to several pulmonary and extra-pulmonary diseases. IPF can be associated with additional comorbidities through other mechanisms as either a cause or a consequence of these diseases. We review the literature regarding the management of common pulmonary and extra-pulmonary comorbidities, including chronic obstructive pulmonary disease, lung cancer, pulmonary hypertension, venous thromboembolism, sleep-disordered breathing, gastroesophageal reflux disease, coronary artery disease, depression and anxiety, and deconditioning. Recent studies have provided some guidance on the management of these diseases in IPF; however, most treatment recommendations are extrapolated from studies of non-IPF patients. Additional studies are required to more accurately determine the clinical features of these comorbidities in patients with IPF and to evaluate conventional treatments and management strategies that are beneficial in non-IPF populations. Keywords: interstitial lung disease, management, idiopathic pulmonary fibrosis, comorbidities

  2. Natural Killer cells and liver fibrosis

    Directory of Open Access Journals (Sweden)

    Frank eFasbender

    2016-01-01

    Full Text Available In the 40 years since the discovery of Natural Killer (NK cells it has been well established that these innate lymphocytes are important for early and effective immune responses against transformed cells and infections with different pathogens. In addition to these classical functions of NK cells, we now know that they are part of a larger family of innate lymphoid cells and that they can even mediate memory-like responses. Additionally, tissue resident NK cells with distinct phenotypical and functional characteristics have been identified. Here we focus on the phenotype of different NK cell subpopulations that can be found in the liver and summarize the current knowledge about the functional role of these cells with a special emphasis on liver fibrosis. NK cell cytotoxicity can contribute to liver damage in different forms of liver disease. However, NK cells can limit liver fibrosis by killing hepatic stellate cell-derived myofibroblasts, which play a key role in this pathogenic process. Therefore, liver NK cells need to be tightly regulated in order to balance these beneficial and pathological effects.

  3. PROFILEing idiopathic pulmonary fibrosis: rethinking biomarker discovery

    Directory of Open Access Journals (Sweden)

    Toby M. Maher

    2013-06-01

    Full Text Available Despite major advances in the understanding of the pathogenesis of idiopathic pulmonary fibrosis (IPF, diagnosis and management of the condition continue to pose significant challenges. Clinical management of IPF remains unsatisfactory due to limited availability of effective drug therapies, a lack of accurate indicators of disease progression, and an absence of simple short-term measures of therapeutic response. The identification of more accurate predictors of prognosis and survival in IPF would facilitate counseling of patients and their families, aid communication among clinicians, and would guide optimal timing of referral for transplantation. Improvements in molecular techniques have led to the identification of new disease pathways and a more targeted approach to the development of novel anti-fibrotic agents. However, despite an increased interest in biomarkers of IPF disease progression there are a lack of measures that can be used in early phase clinical trials. Careful longitudinal phenotyping of individuals with IPF together with the application of novel omics-based technology should provide important insights into disease pathogenesis and should address some of the major issues holding back drug development in IPF. The PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints study is a currently enrolling, prospective cohort study designed to tackle these issues.

  4. Airway inflammation in mild cystic fibrosis.

    Science.gov (United States)

    Eckrich, Jonas; Zissler, Ulrich M; Serve, Friederike; Leutz, Patricia; Smaczny, Christina; Schmitt-Grohé, Sabina; Fussbroich, Daniela; Schubert, Ralf; Zielen, Stefan; Eickmeier, Olaf

    2017-01-01

    Airway infection and inflammation play major roles in the progression of cystic fibrosis (CF) lung disease. In patients with mild disease, airway inflammation is a clinically relevant and often underdiagnosed feature. Lung function, sputum cell counts, and cytokine profiles in CF with mild disease might be different in patients with and without involvement of small airway disease (SAD). Patients with mild CF (n=32) and 22 healthy controls were enrolled in this study. Patients with CF were assigned to two groups: (1) patients without SAD (n=19, median age 12.3years, MEF 25 >50% predicted), and (2) patients with SAD (n=13 median age, 13.2years, MEF 25 inflammation compared to controls as indicated by elevated levels of sputum biomarkers like total cells, neutrophils, and IL6. Our study demonstrated that patients with CF with mild disease defined by lung function might be further endotyped according to their involvement of SAD. In patients with CF and SAD, airway neutrophilic inflammation is more pronounced and is in part distinct from that seen in patients without SAD. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  5. Imaging findings in congenital hepatic fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Akhan, Okan [Department of Radiology, Hacettepe University, School of Medicine, 06100 Ankara (Turkey)]. E-mail: akhano@tr.net; Karaosmanoglu, Ali Devrim [Department of Radiology, Hacettepe University, School of Medicine, 06100 Ankara (Turkey); Ergen, Bilge [Department of Radiology, Hacettepe University, School of Medicine, 06100 Ankara (Turkey)

    2007-01-15

    Congenital hepatic fibrosis (CHF) is a rare congenital multisystemic disorder, mostly inherited in autosomal recessive fashion, primarily affecting renal and hepatobiliary systems. Main underlying process of the disease is the malformation of the ductal plate, the embryological precursor of the biliary system, and secondary biliary strictures and periportal fibrosis ultimately leading to portal hypertension. The natural course of the disease is highly variable ranging from minimally symptomatic disease to true cirrhosis of the liver. However, in most patients the most common manifestations of the diseases that are related to portal hypertension, particularly splenomegaly and bleeding varices. Many other disease processes may co-exist with the disease including Caroli's disease, choledochal cysts and autosomal recessive polycystic kidney disease (ARPKD) reflecting the mulstisystemic nature of the disease. The associating biliary ductal disease led the authors to think that all these entities are a continuum and different reflections of the same underlying pathophysiological process. Although, conventional method of diagnosis of CHF is the liver biopsy the advent of imaging technologies and modalities, today, may permit the correct diagnosis in a non-invasive manner. Characteristic imaging features are generally present and recognition of these findings may obviate liver biopsy while preserving the diagnostic accuracy. In this article, it is aimed to increase the awareness of the practising radiologists to the imaging findings of this uncommon clinical disorder and trail the blaze for future articles relating to this issue.

  6. Pirfenidone treatment of idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Ye Gan

    2011-02-01

    Full Text Available Ye Gan1,2, Erica L Herzog2, Richard H Gomer31Department of Medicine, Central South University, Changsha, Hunan, China; 2Department of Medicine, Yale University School of Medicine, New Haven, CT, USA; 3Department of Biology, Texas A&M University, College Station, TX, USAAbstract: Idiopathic pulmonary fibrosis (IPF is a discrete clinicopathologic entity defined by the presence of usual interstitial pneumonia on high-resolution CT scan and/or open lung biopsy and the absence of an alternate diagnosis or exposure explaining these findings. There are currently no FDA-approved therapies available to treat this disease, and the 5-year mortality is ~80%. The pyridone derivative pirfenidone has been studied extensively as a possible therapeutic agent for use in this deadly disease. This review will present the unique clinical features and management issues encountered by physicians caring for IPF patients, including the poor response to conventional therapy. The biochemistry and preclinical efficacy of pirfenidone will be discussed along with a comprehensive review of the clinical efficacy, safety, and side effects and patient-centered foci such as quality of life and tolerability. It is hoped that this information will lend insight into the complex issues surrounding the use of pirfenidone in IPF and lead to further investigation of this agent as a possible therapy in this devastating disease.Keywords: pirfenidone, fibrosis, clinical trials 

  7. Comparative biology of cystic fibrosis animal models.

    Science.gov (United States)

    Fisher, John T; Zhang, Yulong; Engelhardt, John F

    2011-01-01

    Animal models of human diseases are critical for dissecting mechanisms of pathophysiology and developing therapies. In the context of cystic fibrosis (CF), mouse models have been the dominant species by which to study CF disease processes in vivo for the past two decades. Although much has been learned through these CF mouse models, limitations in the ability of this species to recapitulate spontaneous lung disease and several other organ abnormalities seen in CF humans have created a need for additional species on which to study CF. To this end, pig and ferret CF models have been generated by somatic cell nuclear transfer and are currently being characterized. These new larger animal models have phenotypes that appear to closely resemble human CF disease seen in newborns, and efforts to characterize their adult phenotypes are ongoing. This chapter will review current knowledge about comparative lung cell biology and cystic fibrosis transmembrane conductance regulator (CFTR) biology among mice, pigs, and ferrets that has implications for CF disease modeling in these species. We will focus on methods used to compare the biology and function of CFTR between these species and their relevance to phenotypes seen in the animal models. These cross-species comparisons and the development of both the pig and the ferret CF models may help elucidate pathophysiologic mechanisms of CF lung disease and lead to new therapeutic approaches.

  8. Emerging concepts in biliary repair and fibrosis.

    Science.gov (United States)

    Fabris, Luca; Spirli, Carlo; Cadamuro, Massimiliano; Fiorotto, Romina; Strazzabosco, Mario

    2017-08-01

    Chronic diseases of the biliary tree (cholangiopathies) represent one of the major unmet needs in clinical hepatology and a significant knowledge gap in liver pathophysiology. The common theme in cholangiopathies is that the target of the disease is the biliary tree. After damage to the biliary epithelium, inflammatory changes stimulate a reparative response with proliferation of cholangiocytes and restoration of the biliary architecture, owing to the reactivation of a variety of morphogenetic signals. Chronic damage and inflammation will ultimately result in pathological repair with generation of biliary fibrosis and clinical progression of the disease. The hallmark of pathological biliary repair is the appearance of reactive ductular cells, a population of cholangiocyte-like epithelial cells of unclear and likely mixed origin that are able to orchestrate a complex process that involves a number of different cell types, under joint control of inflammatory and morphogenetic signals. Several questions remain open concerning the histogenesis of reactive ductular cells, their role in liver repair, their mechanism of activation, and the signals exchanged with the other cellular elements cooperating in the reparative process. This review contributes to the current debate by highlighting a number of new concepts derived from the study of the pathophysiology of chronic cholangiopathies, such as congenital hepatic fibrosis, biliary atresia, and Alagille syndrome. Copyright © 2017 the American Physiological Society.

  9. Cystic Fibrosis Related Diabetes: A Case Report

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    Banu Aktaş Yılmaz

    2012-12-01

    Full Text Available The incidence of cystic fibrosis-related diabetes (CFRD has increased, since the life expectancy of cystic fibrosis (CF patients continues to improve. CFRD increases the mortality in patients, because of the negative impacts of CFRD on pulmonary functions. Knowledge of the pathogenesis and course of the disease is essential to administer the appropriate therapy. A thirty-one-year-old CFRD patient, who had hypoglycemia and weight loss under the calorie restriction diet and basal insulin therapy, was admitted to the Endocrinology Department for revision of her therapy. A high-calorie diet considering increased energy demand and multiple insulin injections according the carbohydrate counting were administered to the patient. She gained weight and target blood glucose levels were achieved as a result of this therapy. We present the first case with CFRD followed in our clinic with the review of the literature about the pathogenesis, course and therapy of this disease to draw attention to a special kind of diabetes, which we will encounter more frequently. Turk Jem 2012; 16: 74-8

  10. Imaging the Abdominal Manifestations of Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    C. D. Gillespie

    2017-01-01

    Full Text Available Cystic fibrosis (CF is a multisystem disease with a range of abdominal manifestations including those involving the liver, pancreas, and kidneys. Recent advances in management of the respiratory complications of the disease has led to a greater life expectancy in patients with CF. Subsequently, there is increasing focus on the impact of abdominal disease on quality of life and survival. Liver cirrhosis is the most important extrapulmonary cause of death in CF, yet significant challenges remain in the diagnosis of CF related liver disease. The capacity to predict those patients at risk of developing cirrhosis remains a significant challenge. We review representative abdominal imaging findings in patients with CF selected from the records of two academic health centres, with a view to increasing familiarity with the abdominal manifestations of the disease. We review their presentation and expected imaging findings, with a focus on the challenges facing diagnosis of the hepatic manifestations of the disease. An increased familiarity with these abdominal manifestations will facilitate timely diagnosis and management, which is paramount to further improving outcomes for patients with cystic fibrosis.

  11. Global impact of bronchiectasis and cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Margarida Redondo

    2016-09-01

    To understand variation in the aetiology, microbiology and burden of bronchiectasis and cystic fibrosis across different global healthcare systems.; Bronchiectasis is the term used to refer to dilatation of the bronchi that is usually permanent and is associated with a clinical syndrome of cough, sputum production and recurrent respiratory infections. It can be caused by a range of inherited and acquired disorders, or may be idiopathic in nature. The most well recognised inherited disorder in Western countries is cystic fibrosis (CF, an autosomal recessive condition that leads to progressive bronchiectasis, bacterial infection and premature mortality. Both bronchiectasis due to CF and bronchiectasis due to other conditions are placing an increasing burden on healthcare systems internationally. Treatments for CF are becoming more effective leading to more adult patients with complex healthcare needs. Bronchiectasis not due to CF is becoming increasingly recognised, particularly in the elderly population. Recognition is important and can lead to identification of the underlying cause, appropriate treatment and improved quality of life. The disease is highly diverse in its presentation, requiring all respiratory physicians to have knowledge of the different “bronchiectasis syndromes”. The most common aetiologies and presenting syndromes vary depending on geography, with nontuberculous mycobacterial disease predominating in some parts of North America, post-infectious and idiopathic disease predominating in Western Europe, and post-tuberculosis bronchiectasis dominating in South Asia and Eastern Europe. Ongoing global collaborative studies will greatly advance our understanding of the international impact of bronchiectasis and CF.

  12. Betulinic acid attenuates renal fibrosis in rat chronic kidney disease model.

    Science.gov (United States)

    Sharma, Anshuk; Thakur, Richa; Lingaraju, Madhu C; Kumar, Dhirendra; Mathesh, Karikalan; Telang, Avinash G; Singh, Thakur Uttam; Kumar, Dinesh

    2017-05-01

    Most chronic kidney diseases (CKDs), regardless of the nature of the initial injury, progress to end-stage renal disease (ESRD) characterized by fibrosis with irreversible loss of tissue and function. Thus, improved and more effective therapies are critical. Betulinic acid (BA), a pentacyclic triterpene is a compound in the pipeline of anti-cancer drug development. It has been shown to a possess variety of beneficial effects in many disease conditions. However, its efficacy against CKD is yet to be explored. The present study was undertaken to investigate the effect of BA on renal fibrosis in the rat model of adenine-induced CKD. CKD rats gained significantly less weight during the experimental period when compared to control rats and BA treatment did not significantly increase the weight gain in CKD rats. CKD rats showed elevated levels of serum blood urea nitrogen (BUN), creatinine and uric acid along with increased levels of kidney injury markers such as cystatin C and neutrophil gelatinase-associated lipocalin (NGAL). Further, in comparison to control rats, kidney samples from CKD rats revealed increased profibrotic protein levels like transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), fibronectin, collagen type I and hydroxyproline indicating a progressive fibrotic response. These data are further fortified by histological findings where kidney damage and fibrosis are clearly evident as dilatation of tubules, glomerular degeneration and vacuolation along with deposition of collagen fibers. However, the above-mentioned findings in CKD rats were significantly reversed by BA-treatment revealing its nephroprotective potential and anti-fibrotic activity. The biochemical mechanism of the nephroprotective and anti-fibrotic effect of BA in the adenine-induced CKD rats might be mediated by inhibition of pro-fibrotic protein production thereby hindering the kidney tissue damage along with improvement in kidney function. Thus, BA could be

  13. Leptospira Interrogans Induces Fibrosis in the Mouse Kidney through Inos-Dependent, TLR- and NLR-Independent Signaling Pathways

    Science.gov (United States)

    Fanton d'Andon, Martine; Quellard, Nathalie; Fernandez, Béatrice; Ratet, Gwenn; Lacroix-Lamandé, Sonia; Vandewalle, Alain; Boneca, Ivo G.; Goujon, Jean-Michel; Werts, Catherine

    2014-01-01

    Background Leptospira (L.) interrogans are bacteria responsible for a worldwide reemerging zoonosis. Rodents carry L. interrogans asymptomatically in their kidneys and excrete bacteria in the urine, contaminating the environment. Humans get infected through skin contact and develop a mild or severe leptospirosis that may lead to renal failure and fibrosis. L. interrogans provoke an interstitial nephritis, but the induction of fibrosis caused by L. interrogans has not been studied in murine models. Innate immune receptors from the TLR and NLR families have recently been shown to play a role in the development and progression of tissue fibrosis in the lung, liver and kidneys under different pathophysiological situations. We recently showed that TLR2, TLR4, and NLRP3 receptors were crucial in the defense against leptospirosis. Moreover, infection of a human cell line with L. interrogans was shown to induce TLR2-dependent production of fibronectin, a component of the extracellular matrix. Therefore, we thought to assess the presence of renal fibrosis in L. interrogans infected mice and to analyze the contribution of some innate immune pathways in this process. Methodology/principal findings Here, we characterized by immunohistochemical studies and quantitative real-time PCR, a model of Leptospira-infected C57BL/6J mice, with chronic carriage of L. interrogans inducing mild renal fibrosis. Using various strains of transgenic mice, we determined that the renal infiltrates of T cells and, unexpectedly, TLR and NLR receptors, are not required to generate Leptospira-induced renal fibrosis. We also show that the iNOS enzyme, known to play a role in Leptospira-induced interstitial nephritis, also plays a role in the induction of renal fibrosis. Conclusion/significance To our knowledge, this work provides the first experimental murine model of sustained renal fibrosis induced by a chronic bacterial infection that may be peculiar, since it does not rely on TLR or NLR receptors

  14. Leptospira Interrogans induces fibrosis in the mouse kidney through Inos-dependent, TLR- and NLR-independent signaling pathways.

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    Martine Fanton d'Andon

    Full Text Available BACKGROUND: Leptospira (L. interrogans are bacteria responsible for a worldwide reemerging zoonosis. Rodents carry L. interrogans asymptomatically in their kidneys and excrete bacteria in the urine, contaminating the environment. Humans get infected through skin contact and develop a mild or severe leptospirosis that may lead to renal failure and fibrosis. L. interrogans provoke an interstitial nephritis, but the induction of fibrosis caused by L. interrogans has not been studied in murine models. Innate immune receptors from the TLR and NLR families have recently been shown to play a role in the development and progression of tissue fibrosis in the lung, liver and kidneys under different pathophysiological situations. We recently showed that TLR2, TLR4, and NLRP3 receptors were crucial in the defense against leptospirosis. Moreover, infection of a human cell line with L. interrogans was shown to induce TLR2-dependent production of fibronectin, a component of the extracellular matrix. Therefore, we thought to assess the presence of renal fibrosis in L. interrogans infected mice and to analyze the contribution of some innate immune pathways in this process. METHODOLOGY/PRINCIPAL FINDINGS: Here, we characterized by immunohistochemical studies and quantitative real-time PCR, a model of Leptospira-infected C57BL/6J mice, with chronic carriage of L. interrogans inducing mild renal fibrosis. Using various strains of transgenic mice, we determined that the renal infiltrates of T cells and, unexpectedly, TLR and NLR receptors, are not required to generate Leptospira-induced renal fibrosis. We also show that the iNOS enzyme, known to play a role in Leptospira-induced interstitial nephritis, also plays a role in the induction of renal fibrosis. CONCLUSION/SIGNIFICANCE: To our knowledge, this work provides the first experimental murine model of sustained renal fibrosis induced by a chronic bacterial infection that may be peculiar, since it does not rely on

  15. Immune thrombocytopenia is associated with persistently deranged fibrosis-related seromarker profiles but low bone marrow fibrosis grades

    DEFF Research Database (Denmark)

    Ghanima, Waleed; Boiocchi, Leonardo; Lee, Christina S.

    2018-01-01

    Bone marrow (BM) fibrosis is a potential side effect of thrombopoietin receptor agonist (TPO-RA) treatment. We aimed to investigate stromal seromarker profiles and growth factors in order to elucidate pathogenic and dynamic aspects of immune thrombocytopenia (ITP)-related BM fibrosis before...... and during TPO-RA treatment. Connective tissue metabolites [procollagen I and III peptides (PINP/PIIINP); hyaluronan (HYA), C-terminal-telopeptide (ICTP), and fibrosis-related growth factors (transforming growth factor-beta (TGF-beta), HGF, basic fibroblast growth factor)] were measured in blood samples...... acquired before initiation of TPO-RA and subsequently at 6-month intervals for up to 2 years. BM fibrosis was graded MF-0 in 8 (18%), MF-1 30 (65%), and MF-2 8 (18%) in the last available BM biopsy. In the 21 patients having more than one biopsy, the grade of fibrosis from the first to the last available...

  16. Bupivacaína levógira a 0,5% pura versus mistura enantiomérica de bupivacaína (S75-R25 a 0,5% em anestesia peridural para cirurgia de varizes Bupivacaína levógira a 0,5% pura versus mezcla enantiomerica bupivacaína (S75-R25 a 0,5% en anestesia peridural para cirugía de várices Plain 0.5% levogyrous bupivacaine versus 0.5% bupivacaine enantiomeric mixture (S75-R25 in epidural anesthesia for varicose vein surgery

    Directory of Open Access Journals (Sweden)

    José Delfino

    2001-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A cardiotoxicidade da bupivacaína racêmica (50:50 ainda é a grande variável relacionada à segurança de indicação nos bloqueios regionais que exigem massas e volumes elevados. Recentes experimentações em animais sugerem que a modificação da relação enantiomérica da bupivacaína racêmica poderia contribuir para sua eficácia terapêutica e diminuição de sua toxicidade potencial. O objetivo do presente estudo foi comparar a eficiência da mistura enantiomérica de bupivacaína (S75-R25 com a levógira pura S(-100 na anestesia peridural lombar para cirurgias de varizes dos membros inferiores. MÉTODO: O estudo envolveu 30 pacientes do sexo feminino com idades entre 15 e 65 anos, estado físico ASA I ou II, programados para cirurgia eletiva de varizes. Em teste aleatório e duplamente encoberto, os pacientes foram divididos em dois grupos de 15: Grupo S75-R25 - 20 ml (100 mg de mistura enantiomérica de bupivacaína a 0,5% (S75-R25 - e Grupo Levógiro - 20 ml (100 mg de bupivacaína levógira S(-100% a 0,5% sem adjuvante. Foram comparadas as características dos bloqueios sensitivo e motor bem como a incidência de efeitos colaterais. RESULTADOS: Foram detectadas diferenças intergrupais relacionadas às características demográficas e um maior tempo cirúrgico no grupo S75-R25. A dispersão mais rápida e a menor potência analgésica da mistura isomérica exibiram significância estatística. Não houve diferença significativa relacionada à ocorrência de efeitos colaterais. O grupo levógiro apresentou menor relaxamento muscular. CONCLUSÕES: A redução da incidência de efeitos colaterais, a receptividade do método pelos pacientes, a ausência de sintomatologia neurológica transitória pós-operatória apontam para a aplicação segura de ambas as soluções em anestesia peridural lombar para cirurgia de varizes dos membros inferiores. A casuística, entretanto, não é ainda suficiente para

  17. Estudo comparativo entre soluções a 0,5% de levobupivacaína, bupivacaína em excesso enantiomérico de 50% e bupivacaína racêmica em anestesia peridural para cirurgia de abdômen inferior Estudio comparativo entre soluciones a 0,5% de levobupivacaína, bupivacaína en exceso enantiomérico del 50% y bupivacaína racémica en anestesia peridural para cirugía de abdomen inferior Levobupivacaine 0.5%, 50% enantiomeric excess bupivacaine and racemic bupivacaine in epidural anesthesia for lower abdominal procedures. Comparative study

    Directory of Open Access Journals (Sweden)

    Pedro Paulo Tanaka

    2005-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Com a finalidade de encontrar um anestésico local mais seguro que a bupivacaína, vários estudos em animais foram realizados com seus isômeros. Este estudo teve como objetivo avaliar a eficácia da bupivacaína em excesso enantiomérico de 50%, comparada à levobupivacaína e à bupivacaína racêmica, na anestesia peridural em pacientes submetidos à cirurgia de abdômen inferior, pelo período de uma hora após a injeção das soluções. MÉTODO: Após aprovação pelo Comitê de Ética em Pesquisa, participaram deste estudo, aleatório e duplamente encoberto, 87 pacientes com idade entre 18 e 65 anos, estado físico ASA I e II submetidos à cirurgia de abdômen inferior. Foram distribuídos em três grupos que receberam fracionadamente solução contendo 27 mL (incluindo a dose-teste de anestésico local com adrenalina (1:200.000 e fentanil (100 µg. O grupo I recebeu solução de levobupivacaína a 0,5%, o grupo II recebeu solução de bupivacaína em excesso enantiomérico de 50% a 0,5% e o grupo III recebeu solução de bupivacaína a 0,5%. Os pacientes foram monitorizados por meio de oxímetro de pulso, cardioscópio e pressão arterial não-invasiva. Foram investigadas as características motoras e sensitivas do bloqueio anestésico, bem como a incidência de efeitos colaterais. Os frascos de anestésico local foram preparados sem identificação, numerados e somente ao final do estudo a lista de distribuição aleatória foi aberta. RESULTADOS: Não foram observadas diferenças significativas com relação à altura e estado físico. Diferença demográfica significativa foi encontrada em relação à idade no grupo I. Os parâmetros hemodinâmicos foram semelhantes entre os grupos. Houve diferença significativa em relação à intensidade do bloqueio motor relatado entre os grupos estudados (menor intensidade no grupo I comparada aos grupos II e III. CONCLUSÕES: Foram observados adequados bloqueios

  18. Avaliação da profundidade do espaço peridural com o uso do ultrassom Evaluación de la profundidad del espacio epidural con el uso del ultrasonido Evaluating the depth of the epidural space with the use of ultrasound

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    Pablo Escovedo Helayel

    2010-08-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O objetivo deste estudo foi avaliar o uso do ultrassom na determinação da profundidade do espaço peridural. MÉTODO: Sessenta pacientes foram alocados prospectivamente tendo a identificação do espaço intervertebral L3-L4 inicialmente feita pelo método palpatório. Posteriormente, utilizou-se o método ultrassonográfico, realizando-se a medida da profundidade do espaço peridural (PU. Após a punção peridural, foram anotadas as medidas da profundidade (PA. Realizaram-se estatísticas descritivas dos dados e calculou-se o coeficiente de correlação de concordância e análise de Bland-Altman, com intervalo de 95% de confiança para as medidas de profundidade. RESULTADOS: A análise de concordância entre o método palpatório e ultrassonográfico foi de 86,6%. Foram obtidos valores médios de PU 4,97 ± 0,51 cm e PA 4,97 ± 0,71 cm e coeficiente de correlação de Pearson de 0,66, enquanto a análise Bland-Altman revelou diferença média de 0,0035 ± 0,53 cm, com limite de 95% de confiança entre -0,228 a 0,221. CONCLUSÕES: A ultrassonografia é uma ferramenta precisa para a determinação da profundidade do espaço peridural.JUSTIFICATIVA Y OBJETIVOS: El objetivo de este estudio fue evaluar el uso del ultrasonido para la determinación de la profundidad del espacio epidural. MÉTODO: Sesenta pacientes fueron ubicados, prospectivamente teniendo la identificación del espacio intervertebral L3-L4 inicialmente realizada por el método de palpación. Posteriormente se usó el método de ultrasonido, y se realizó la medida de la profundidad del espacio epidural (PU. Después de la punción epidural, se anotaron las medidas de la profundidad (PA. Se midieron las estadísticas descriptivas de los datos y se calculó el coeficiente de correlación de concordancia y análisis de Bland-Altman, con un intervalo de un 95% de confianza para las medidas de profundidad. RESULTADOS: El análisis de concordancia entre el m

  19. Recent data concerning heparanase: focus on fibrosis, inflammation and cancer.

    Science.gov (United States)

    Secchi, Maria Francesca; Masola, Valentina; Zaza, Gianluigi; Lupo, Antonio; Gambaro, Giovanni; Onisto, Maurizio

    2015-12-01

    Heparanase (HPSE) is a multitasking protein characterized by enzymatic and non-enzymatic activities. By means of its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans, thereby inducing the remodeling of the extracellular matrix and basement membranes. Thanks to the cleavage of HS, HPSE also promotes the release and diffusion of several HS-linked molecules such as growth factors, cytokines and enzymes. In addition to degrading HS chains, HPSE has non-enzymatic functions that trigger several signaling pathways. This signaling activity is achieved by interacting with transmembrane proteins, activating kinases such as Akt and Src, or modulating the activity of factors such as FGF-2 and TGF-β. Several studies have recently highlighted a possible intracellular activity for HPSE, particularly at nuclear level. While HPSE activity is quite limited in physiological conditions, its demonstrated increasing involvement in various pathological conditions, such as in tumor progression and renal disease, have attracted the attention of a growing number of researchers. The fact that no other molecule is capable of performing the same function as HPSE makes this enzyme an attractive potential target of medical treatment. With this short conceptual overview, we aim to provide an update on current knowledge concerning the HPSE protein in the experimental and clinical settings, paying particular attention to its role in fibrosis, inflammation and cancer.

  20. Non-invasive ventilation for cystic fibrosis.

    Science.gov (United States)

    Moran, Fidelma; Bradley, Judy M; Piper, Amanda J

    2017-02-20

    Non-invasive ventilation may be a means to temporarily reverse or slow the progression of respiratory failure in cystic fibrosis by providing ventilatory support and avoiding tracheal intubation. Using non-invasive ventilation, in the appropriate situation or individuals, can improve lung mechanics through increasing airflow and gas exchange and decreasing the work of breathing. Non-invasive ventilation thus acts as an external respiratory muscle. This is an update of a previously published review. To compare the effect of non-invasive ventilation versus no non-invasive ventilation in people with cystic fibrosis for airway clearance, during sleep and during exercise. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We searched the reference lists of each trial for additional publications possibly containing other trials.Most recent search: 08 August 2016. Randomised controlled trials comparing a form of pressure preset or volume preset non-invasive ventilation to no non-invasive ventilation used for airway clearance or during sleep or exercise in people with acute or chronic respiratory failure in cystic fibrosis. Three reviewers independently assessed trials for inclusion criteria and methodological quality, and extracted data. Ten trials met the inclusion criteria with a total of 191 participants. Seven trials evaluated single treatment sessions, one evaluated a two-week intervention, one evaluated a six-week intervention and one a three-month intervention. It is only possible to blind trials of airway clearance and overnight ventilatory support to the outcome assessors. In most of the trials we judged there was an unclear risk of bias with regards to blinding due to inadequate descriptions. The six-week trial was the only one judged to have a low risk of bias for all

  1. Wnt-induced secreted protein 1/CCN4 in liver fibrosis both in vitro and in vivo.

    Science.gov (United States)

    Jian, Yi-Cheng; Wang, Jin-Jun; Dong, Shuang; Hu, Jun-Wei; Hu, Li-Juan; Yang, Gen-Mei; Zheng, Ya-Xin; Xiong, Wu-Jun

    2014-01-01

    Wnt-induced secreted protein-1 (WISP-1/CCN4) is a member of the CCN family growth factors, and its role in liver fibrosis is largely unknown. For in vitro, hepatic stellate cells (HSCs) were isolated from Sprague-Dawley rats. Expression of WISP-1 during progressive activation of cultured rat HSCs was analyzed by qRT-PCR. The effects of TNF-a and TGF-beta1 on WISP-1 expression were analyzed in stellate cell lines HSC-T6 and LX-2. The effect of exogenous WISP-1 protein on LX-2 proliferation was examined. For in vivo, expressions of WISP-1 in fibrotic liver of a carbon tetrachloride (CCl4)-induced fibrosis rat model were analyzed by qRT-PCR and immunohistochemistry. In vitro, WISP-1 was increasingly expressed during progressive activation of cultured rat HSCs. WISP-1 was significantly induced in HSC-T6 cells by TNF-a and in LX-2 cells by TGF-beta1. Recombinant WISP-1 protein promoted LX-2 proliferation in a dose-dependent manner. In vivo, both mRNA and protein expression levels of WISP-1 were increased significantly in experimental hepatic fibrosis model. Our results showed the upregulation of WISP-1 in both in vitro and in vivo liver fibrosis models, and WISP-1 stimulated the proliferation of HSCs in vitro. These results may be helpful to elucidate the exact role of WISP-1 in liver fibrogenesis.

  2. Antisense oligonucleotide inhibition of Heat Shock Protein (HSP 47 improves bleomycin-induced pulmonary fibrosis in rats

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    Noguchi Takayuki

    2007-05-01

    Full Text Available Abstract Background The most common pathologic form of pulmonary fibrosis arises from excessive deposition of extracellular matrix proteins such as collagen. The 47 kDa heat shock protein 47 (HSP47 is a collagen-specific molecular chaperone that has been shown to play a major role during the processing and/or secretion of procollagen. Objectives To determine whether inhibition of HSP47 could have beneficial effects in mitigating bleomycin-induced pulmonary fibrosis in rats. Methods All experiments were performed with 250–300 g male Wistar rats. Animals were randomly divided into five experimental groups that were administered: 1 saline alone, 2 bleomycin alone, 3 antisense HSP47 oligonucleotides alone, 4 bleomycin + antisense HSP47 oligonucleotides, and 5 bleomycin + sense control oligonucleotides. We investigated lung histopathology and performed immunoblot and immunohistochemistry analyses. Results In rats treated with HSP47 antisense oligonucleotides, pulmonary fibrosis was significantly reduced. In addition, treatment with HSP47 antisense oligonucleotides significantly improved bleomycin-induced morphological changes. Treatment with HSP47 antisense oligonucleotides alone did not produce any significant changes to lung morphology. Immunoblot analyses of lung homogenates confirmed the inhibition of HSP47 protein by antisense oligonucleotides. The bleo + sense group, however, did not exhibit any improvement in lung pathology compared to bleomycin alone groups, and also had no effect on HSP47 expression. Conclusion These findings suggest that HSP47 antisense oligonucleotide inhibition of HSP47 improves bleomycin-induced pulmonary fibrosis pathology in rats.

  3. Can we prevent, reduce or reverse intestinal fibrosis in IBD?

    Science.gov (United States)

    Latella, G; Sferra, R; Speca, S; Vetuschi, A; Gaudio, E

    2013-05-01

    Intestinal fibrosis is a common complication of in inflammatory bowel disease (IBD) and can occur in both ulcerative colitis (UC) and Crohn's disease (CD), but is much more prevalent in CD. Fibrosis is a consequence of local chronic inflammation and is characterized by abnormal deposition of extracellular matrix (ECM) proteins producted by activated myofibroblasts. Current anti-inflammatory therapies used in IBD do not prevent nor they reverse established fibrosis and strictures. Despite the therapeutic advance in the treatment of IBD in the last two decades, the incidence of intestinal strictures in CD has not significantly changed. This implies that control of intestinal inflammation does not necessarily affect the associated fibrotic process. The conventional view that intestinal fibrosis is an inevitable and irreversible process in patients with IBD is progressively changing in light of improved understanding of the cellular and molecular mechanisms that underline the pathogenesis of fibrosis. Comprehension of the mechanisms of intestinal fibrosis may pave the way for the developments of anti-fibrotic agents and of new possible therapeutic approches in IBD. Nevertheless, there are important clinical issues that need further investigations, in particular the identification of factors relevant for the development of the intestinal fibrosis in IBD and the need of accurate and effective monitoring of the fibrotic progression and of effectiveness of the new proposed treatments.

  4. Mechanisms of initiation and progression of intestinal fibrosis in IBD.

    Science.gov (United States)

    Latella, Giovanni; Di Gregorio, Jacopo; Flati, Vincenzo; Rieder, Florian; Lawrance, Ian C

    2015-01-01

    Intestinal fibrosis is a common complication of the inflammatory bowel diseases (IBDs). It becomes clinically apparent in >30% of patients with Crohn's disease (CD) and in about 5% with ulcerative colitis (UC). Fibrosis is a consequence of local chronic inflammation and is characterized by excessive extracellular matrix (ECM) protein deposition. ECM is produced by activated myofibroblasts, which are modulated by both, profibrotic and antifibrotic factors. Fibrosis depends on the balance between the production and degradation of ECM proteins. This equilibrium can be impacted by a complex and dynamic interaction between profibrotic and antifibrotic mediators. Despite the major therapeutic advances in the treatment of active inflammation in IBD over the past two decades, the incidence of intestinal strictures in CD has not significantly changed as the current anti-inflammatory therapies neither prevent nor reverse the established fibrosis and strictures. This implies that control of intestinal inflammation does not necessarily affect the associated fibrotic process. The conventional view that intestinal fibrosis is an inevitable and irreversible process in patients with IBD is also gradually changing in light of an improved understanding of the cellular and molecular mechanisms that underline the pathogenesis of fibrosis. Comprehension of the mechanisms of intestinal fibrosis is thus vital and may pave the way for the developments of antifibrotic agents and new therapeutic approaches in IBD.

  5. Ormond's disease or secondary retroperitoneal fibrosis? An overview of retroperitoneal fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Heckmann, M.; Uder, M.; Kuefner, M.A.; Heinrich, M.C. [Universitaetsklinikum Erlangen (Germany). Radiologisches Inst.

    2009-04-15

    Retroperitoneal fibrosis represents a rare inflammatory disease. About two thirds of all cases seem to be idiopathic (= Ormond's disease). The remaining one third is secondary and may be ascribed to infections, trauma, radiation therapy, malignant diseases, and the use of certain drugs. Up to 15 % of patients have additional fibrotic processes outside the retroperitoneum. The clinical symptoms of retroperitoneal fibrosis are non-specific. In sonography retroperitoneal fibrosis appears as a retroperitoneal hypoechoic mass which can involve the ureters and thus cause hydronephrosis. Intravenous urography and MR urography can demonstrate the typical triad of medial deviation and extrinsic compression of the ureters and hydronephrosis. CT and MRI are the modalities of choice for the diagnosis and follow-up of this disease. The lesion typically begins at the level of the fourth or fifth lumbar vertebra and appears as a plaque, encasing the aorta and the inferior vena cava and often enveloping and medially displacing the ureters. In unenhanced CT, retroperitoneal fibrosis appears as a mass that is isodense with muscle. When using MRI, the mass is hypointense in T1-weighted images and of variable intensity in T2-weighted images according to its stage: it may be hyperintense in early stages, while the tissue may have a low signal in late stages. After the administration of contrast media, enhancement is greatest in the early inflammatory phase and minimal in the late fibrotic phase. Dynamic gadolinium enhancement can be useful for assessing disease activity, monitoring response to treatment, and detecting relapse. To differentiate retroperitoneal masses, diffusion-weighted MRI may provide useful information. (orig.)

  6. Effects of leflunomide on inflamation and fibrosis in bleomycine induced pulmonary fibrosis in wistar albino rats.

    Science.gov (United States)

    Kayhan, Servet; Guzel, Aygul; Duran, Latif; Tutuncu, Serife; Guzel, Ahmet; Gunaydın, Mithat; Salis, Osman; Okuyucu, Ali; Selcuk, Mustafa Yasin

    2013-10-01

    Pulmonary fibrosis is a rare and progressive lung disease with a high mortality rate. The treatment regimens still fail to recover the disease. Leflunomide (LEF) is an immunomodulatory agent with antiproliferative activity that is used for the treatment of rheumatoid arthritis. The purpose of the study is to investigate the potential therapeutic efficacy of LEF in bleomycin (BLM) induced pulmonary fibrosis. A total of 21 male, adult wistar albino rats were used. The animals were divided into three groups as control, BLM and BLM plus LEF groups (n=7). In BLM group, mice were treated with intratracheal instillation of BLM (2.5 U/kg). Control group received the same volume of saline instead of BLM. In LEF group, in addition to BLM, LEF (10 mg/kg, daily) was administrated by oral gavage. The effect of LEF on pulmonary inflammation and fibrosis was studied by measurements of serum clara cell protein-16 (CC-16), thiobarbituric acid reactive substance levels (TBARS), superoxide dismutase (SOD) and advanced oxidation protein products (AOPP) levels and lung tissue contents of IL-6, TNF-α and NF-κB by immunhistochemical examinations. LEF significantly increased the level of CC-16 and decreased the level of AOPP (P=0.042 and P=0.003 respectively). Lung tissue contents of IL-6, TNF-α and NF-κB significantly decreased in LEF group compared to BLM group by immunhistochemical examinations (P<0.001). LEF reduces oxidative stress factors, alveolar inflammation and attenuates lung injury and fibrosis.

  7. Activated MCTC mast cells infiltrate diseased lung areas in cystic fibrosis and idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Löfdahl Claes-Göran

    2011-10-01

    Full Text Available Abstract Background Although mast cells are regarded as important regulators of inflammation and tissue remodelling, their role in cystic fibrosis (CF and idiopathic pulmonary fibrosis (IPF has remained less studied. This study investigates the densities and phenotypes of mast cell populations in multiple lung compartments from patients with CF, IPF and never smoking controls. Methods Small airways, pulmonary vessels, and lung parenchyma were subjected to detailed immunohistochemical analyses using lungs from patients with CF (20 lung regions; 5 patients, IPF (21 regions; 7 patients and controls (16 regions; 8 subjects. In each compartment the densities and distribution of MCT and MCTC mast cell populations were studied as well as the mast cell expression of IL-6 and TGF-β. Results In the alveolar parenchyma in lungs from patients with CF, MCTC numbers increased in areas showing cellular inflammation or fibrosis compared to controls. Apart from an altered balance between MCTC and MCT cells, mast cell in CF lungs showed elevated expression of IL-6. In CF, a decrease in total mast cell numbers was observed in small airways and pulmonary vessels. In patients with IPF, a significantly elevated MCTC density was present in fibrotic areas of the alveolar parenchyma with increased mast cell expression of TGF-β. The total mast cell density was unchanged in small airways and decreased in pulmonary vessels in IPF. Both the density, as well as the percentage, of MCTC correlated positively with the degree of fibrosis. The increased density of MCTC, as well as MCTC expression of TGF-β, correlated negatively with patient lung function. Conclusions The present study reveals that altered mast cell populations, with increased numbers of MCTC in diseased alveolar parenchyma, represents a significant component of the histopathology in CF and IPF. The mast cell alterations correlated to the degree of tissue remodelling and to lung function parameters. Further

  8. Impaired Lymphocyte Profile in Schistosomiasis Patients with Periportal Fibrosis

    Directory of Open Access Journals (Sweden)

    Luciana Santos Cardoso

    2013-01-01

    Full Text Available The Th2 immune response in chronic schistosomiasis is associated with the development of periportal fibrosis. However, little is known about the phenotype and activation status of T cells in the process. Objective. To evaluate the profile of T cells in schistosomiasis patients with periportal fibrosis. Methods. It was a cross-sectional study, conducted in the village of Agua Preta, Bahia, Brazil, which included 37 subjects with periportal fibrosis determined by ultrasound. Peripheral blood mononuclear cells were obtained by the Ficcol-hypaque gradient and the frequency of T cells expressing the surface markers CD28, CD69, CD25, and CTLA-4 was determined by flow cytometry. Results. The frequency of CD4+CD28+ T lymphocytes was higher in individuals with moderate to severe fibrosis compared to patients with incipient fibrosis. We did not observe any significant difference in the frequency of CD4+ T cells expressing CD69 among groups of individuals. There was also no significant difference in the frequency of CD8+ T cells expressing CD28 or CD69 among the studied groups. Individuals with moderate to severe fibrosis presented a lower frequency of CD8+ T cells, CD4+CD25high T cells, and CD4+CTLA-4+ T cells when compared to patients without fibrosis or incipient fibrosis. The frequency of CD4+CD25low cells did not differ between groups. Conclusion. The high frequency of activated T cells coinciding with a low frequency of putative Treg cells may account for the development of periportal fibrosis in human schistosomiasis.

  9. Accuracy of FibroScan for diagnosing liver fibrosis

    Directory of Open Access Journals (Sweden)

    Jian ZHANG

    2011-11-01

    Full Text Available Objective To evaluate the accuracy of transient elastometry(FibroScan for the detection of liver fibrosis.Methods A total of 323 patients diagnosed with chronic liver disease based on pathological examination in the 302 Hospital of the People’s Liberation Army from April to December of 2009 were involved in the current study.Among them,141 patients were subjected to liver biopsy.Their liver function,coagulant index,B-ultrasound and blood cell count were examined clinically.Four examinations related to liver fibrosis were done on some of the patients.Meanwhile,FibroScan was used for liver stiffness measurement(LSM of every patient.The correlation between liver stiffness and the serologic index and liver fibrosis degree was analyzed.The Receive Operating Characteristic(ROC curve was adopted to analyze the accuracy of FibroScan for diagnosing liver fibrosis.Results Each serologic index was significantly correlated with liver stiffness(P < 0.001,and liver stiffness was closely related to the stage of liver fibrosis(r=0.74,P < 0.001.The statistical results of the 141 patients who underwent pathologic examination show that the areas under the ROC curve were 0.97(0.94,1.00 for patients with portal fibrosis(F1,0.96(0.93,0.99 for patients with significant fibrosis(F2,0.99(0.98,1.00 for patients with severe fibrosis(F3,and 0.97(0.94,0.99 for patients with cirrhosis(F4.The cutoff values were 4.4KPa,6.8KPa,9.7KPa,and 10.0KPa,respectively.Conclusion FibroScan is valuable for the diagnosis of liver fibrosis.It can be used as the basis for follow-up and management of patients with chronic liver diseases.

  10. Combined pulmonary fibrosis and emphysema (CPFE): an entity different from emphysema or pulmonary fibrosis alone

    Science.gov (United States)

    Lin, Huijin

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) and idiopathic interstitial pneumonias (IIP), with different radiological, pathological, functional and prognostic characteristics, have been regarded as separate entities for a long time. However, there is an increasing recognition of the coexistence of emphysema and pulmonary fibrosis in individuals. The association was first described as a syndrome by Cottin in 2005, named “combined pulmonary fibrosis and emphysema (CPFE)”, which is characterized by exertional dyspnea, upper-lobe emphysema and lower-lobe fibrosis, preserved lung volume and severely diminished capacity of gas exchange. CPFE is frequently complicated by pulmonary hypertension, acute lung injury and lung cancer and prognosis of it is poor. Treatments for CPFE patients with severe pulmonary hypertension are less effective other than lung transplantation. However, CPFE has not yet attracted wide attention of clinicians and there is no research systematically contrasting the differences among CPFE, emphysema/COPD and IIP at the same time. The authors will review the existing knowledge of CPFE and compare them to either entity alone for the first time, with the purpose of improving the awareness of this syndrome and exploring novel effective therapeutic strategies in clinical practice. PMID:25973246

  11. Epithelial-mesenchymal transition: An emerging target in tissue fibrosis

    Science.gov (United States)

    Li, Meirong; Luan, Fuxin; Zhao, Yali; Hao, Haojie; Zhou, Yong; Han, Weidong

    2016-01-01

    Epithelial-mesenchymal transition (EMT) is involved in a variety of tissue fibroses. Fibroblasts/myofibroblasts derived from epithelial cells contribute to the excessive accumulation of fibrous connective tissue in damaged tissue, which can lead to permanent scarring or organ malfunction. Therefore, EMT-related fibrosis cannot be neglected. This review highlights the findings that demonstrate the EMT to be a direct contributor to the fibroblast/myofibroblast population in the development of tissue fibrosis and helps to elucidate EMT-related anti-fibrotic strategies, which may enable the development of therapeutic interventions to suppress EMT and potentially reverse organ fibrosis. PMID:26361988

  12. Diabetes mellitus in childhood cystic fibrosis.

    LENUS (Irish Health Repository)

    Rauf, F

    2012-02-03

    Since 1984, five patients in the cystic fibrosis (CF) clinic at Cork Regional Hospital have developed diabetes mellitus (DM) and were treated with Insulin. None had received systemic corticosteroids but two had high calorie naso-gastric feeding regimes. Two died from lung disease. A fifteen year old boy developed bilateral cataracts. In nine other paediatric CF clinics in the Republic of Ireland (total: 420 patients), three patients have DM, two receiving Insulin. Abnormal glucose tolerance is becoming more common in CF as patients survive longer. The possible role of corticosteroid treatment and intensive carbohydrate feeding regimes in development of glucose intolerance must be considered. DM in CF differs from the usual childhood DM. Regular screening and early Insulin supplementation may be beneficial.

  13. Aerosolized antibiotics in cystic fibrosis: an update.

    Science.gov (United States)

    Fiel, Stanley B

    2014-06-01

    Inhaled antibiotic therapy, targeting Pseudomonas aeruginosa, is a fundamental component of cystic fibrosis (CF) management. Tobramycin inhalation solution (TIS) was approved in the United States (US) in 1998. Subsequent research efforts focused on developing products with a reduced treatment time burden. Aztreonam for inhalation solution (AZLI), administered via a more efficient nebulizer than TIS, was approved in the US in 2010. Dry powder for inhalation (DPI) formulations provide alternatives to nebulized therapy: tobramycin powder for inhalation (also known as TIP™) was approved in the US in 2013, and colistimethate sodium DPI received European approval in 2012. Other aerosolized antibiotics and regimens combining inhaled antibiotics are in development. Inhaled antibiotic rotation (e.g., TIS alternating with AZLI) is an important concept being actively tested in CF.

  14. Barriers to adherence in cystic fibrosis

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Schiøtz, Peter Oluf

    2012-01-01

    Objectives: The objectives of the present study was to explore barriers to treatment adherence perceived by young CF patients and their parents and to identify what kind of support the young patients and their parents request from the CF center. Methods: A questionnaire survey of a cohort of young...... Danish patients with cystic fibrosis aged 14 to 25 years and their parents. Conclusions: The present study showed that the majority of adolescents with CF and their parents experienced barriers to treatment adherence. Patients and parents agreed that the three most common barriers encountered lack...... of time, forgetfulness and unwillingness to take medication in public. A significant, positive correlation was found between the number of barriers and the perceived treatment burden. Additionally, we found that almost half of the adolescents and half of the parents conveyed a desire for more information...

  15. Pubertal development in cystic fibrosis: an overview.

    Science.gov (United States)

    Arrigo, Teresa; Rulli, I; Sferlazzas, C; De Luca, Filippo

    2003-03-01

    Cystic fibrosis (CF) is an autosomal recessive disease characterized by respiratory and intestinal insufficiencies. It has been reported in the literature that patients with CF show delayed growth and puberty and girls with CF achieve menarche at older age than normal females. Infertility, in both sexes, and menstrual dysfunction, in girls, are common in patients with CF. Previous data suggest that the degree of failure of growth and development is correlated with malnutrition and severity of progressing pulmonary disease. Despite improved nutrition and intensive treatment, patients with CF have delayed puberty and growth pubertal spurt. This maturational lag is accompanied by a significant delay in attaining pubertal levels of insulin-like growth factor-I (IGF-I), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex steroid hormones.

  16. Retroperitoneal fibrosis - a report of five cases.

    Science.gov (United States)

    Runowska, Marta; Majewski, Dominik; Puszczewicz, Mariusz

    2017-01-01

    Retroperitoneal fibrosis (RPF) is a rare disease, characterized by inflammation and deposition of fibrotic tissue in the vicinity of the abdominal aorta and iliac arteries. We present a report of five patients admitted to our department between January 2014 and February 2017, diagnosed with RPF. Abdominal pain was the most common presenting symptom; however, in one patient, RPF was identified accidentally in routinely performed ultrasonography. In 4 cases, corticosteroids (CS) in combination with azathioprine were applied as first-line therapy, whereas one patient was treated with intravenous methylprednisolone pulses followed by oral CS. In this paper, clinical features as well as laboratory and radiographic findings together with management and treatment outcomes in patients with RPF are discussed. Given the rarity of the condition, it seems important to report every single case of RPF to help establish its management algorithm.

  17. Nephrogenic systemic fibrosis: clinical picture and treatment

    DEFF Research Database (Denmark)

    Marckmann, Peter; Skov, Lone

    2009-01-01

    , and the histology of deep skin biopsies. Symptomatic treatment with intensive physiotherapy and painkillers is important, but there is no known curative medical treatment. Spontaneous remission of NSF symptoms may occur with recovery of renal function after an episode of acute renal failure, or with kidney......The classic hallmark symptoms of advanced nephrogenic systemic fibrosis (NSF) (skin thickening, hardening and hyperpigmentation, and disabling contractures in renal failure patients) in temporal association with Gd-based contrast agent (GBCA) exposure are almost pathognomonic of NSF. Less obvious...... cases may be diagnosed on the basis of history of early GBCA-related NSF symptoms (warm swellings, pain, discoloration, itching of lower legs), signs of multiorgan involvement (lungs, nervous system), the exclusion of differential diagnoses, including scleromyxedema and systemic sclerosis...

  18. Pleural fibrosis associated with dihydroergocryptine treatment.

    Science.gov (United States)

    Oechsner, M; Groenke, L; Mueller, D

    2000-04-01

    This is the first report of a histologically confirmed pleuropulmonary fibrosis (PPF) associated with the dopamine agonist dihydroergocryptine. A 67-year-old male patient with Parkinson's disease developed a severe restrictive pulmonary disorder with dyspnea and nonproductive cough after a daily intake of 45 mg dihydroergocryptine for 2 years. After changing the dopamine agonist to the non-ergoline substance pramipexole, marked improvement of the clinical symptoms of PPF occurred, while radiological signs showed only a moderate decrease. PPF is a possibly fatal complication. Chest X-rays and specific pneumological diagnostics should be done if typical symptoms or nonspecific signs of PPF occur while a patient is on treatment with an ergoline dopamine agonist.

  19. Pseudomonas aeruginosa biofilms in cystic fibrosis

    DEFF Research Database (Denmark)

    Høiby, Niels; Ciofu, Oana; Bjarnsholt, Thomas

    2010-01-01

    of mutations, slow growth and adaptation of the bacteria to the conditions in the lungs, and to antibiotic therapy. Low bacterial metabolic activity and increase of doubling times of the bacterial cells in CF lungs are responsible for some of the tolerance to antibiotics. Conventional resistance mechanisms......, such as chromosomal ß-lactamase, upregulated efflux pumps, and mutations of antibiotic target molecules in the bacteria, also contribute to the survival of P. aeruginosa biofilms. Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy, and they can be treated by chronic suppressive therapy.......The persistence of chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients is due to biofilm-growing mucoid (alginate-producing) strains. A biofilm is a structured consortium of bacteria, embedded in a self-produced polymer matrix consisting of polysaccharide, protein...

  20. A cystic fibrosis pancreatic adenocarcinoma cell line.

    Science.gov (United States)

    Schoumacher, R A; Ram, J; Iannuzzi, M C; Bradbury, N A; Wallace, R W; Hon, C T; Kelly, D R; Schmid, S M; Gelder, F B; Rado, T A

    1990-05-01

    We established a pancreatic adenocarcinoma cell line (CFPAC-1) from a patient with cystic fibrosis (CF) and assessed some of its properties. The cells show epithelial morphology and express cytokeratin and oncofetal antigens characteristic of pancreatic duct cells. Basal and stimulated levels of cAMP and cAMP-dependent protein kinase and the biophysical properties of single Cl- channels in CFPAC-1 are similar to those of airway and sweat gland primary cultures and Cl(-)-secreting epithelial cell lines. Anion transport and single Cl- channel activity was stimulated by Ca2+ ionophores but not by forskolin, cAMP analogs, or phosphodiesterase inhibitors. The cells express the CF gene and manifest the most common CF mutation, deletion of three nucleotides resulting in a phenylalanine-508 deletion. These properties have been stable through greater than 80 passages (24 months), suggesting that CFPAC-1 can serve as a continuous cell line that displays the CF defect.