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1.
Ann Rheum Dis ; 77(3): 393-398, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29146737

RESUMO

OBJECTIVES: To evaluate the prevalence and type of rheumatic immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs), as well as the correlation with tumour response. METHODS: This was a single-centre prospective observational study including all cancer patients receiving ICIs. The occurrence of irAEs and tumour response was assessed on a regular basis. Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management. RESULTS: From September 2015 to May 2017, 524 patients received ICIs and 35 were referred to the department of rheumatology (6.6%). All but one of the rheumatic irAEs occurred with anti-programmed cell death protein 1(PD-1)/PD-1 ligand 1(PD-L1) antibodies, with a median exposure time of 70 days. There were two distinct clinical presentations: (1) inflammatory arthritis (3.8%) mimicking either rheumatoid arthritis (n=7), polymyalgia rheumatica (n=11) or psoriatic arthritis (n=2) and (2) non-inflammatory musculoskeletal conditions (2.8%; n=15). One patient with rheumatoid arthritis was anti-cyclic citrullinated peptide (anti-CCP) positive. Nineteen patients required glucocorticoids, and methotrexate was started in two patients. Non-inflammatory disorders were managed with non-steroidal anti-inflammatory drugs, analgesics and/or physiotherapy. ICI treatment was pursued in all but one patient. Patients with rheumatic irAEs had a higher tumour response rate compared with patients without irAEs (85.7% vs 35.3%; P<0.0001). CONCLUSION: Since ICIs are used with increasing frequency, knowledge of rheumatic irAEs and their management is of major interest. All patients were responsive either to low-to-moderate doses of prednisone or symptomatic therapies and did not require ICI discontinuation. Furthermore, tumour response was significantly higher in patients who experienced rheumatic irAEs.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias/tratamento farmacológico , Doenças Reumáticas/induzido quimicamente , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Estudos de Coortes , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Doenças Reumáticas/epidemiologia
2.
Langmuir ; 29(4): 1206-10, 2013 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-23244532

RESUMO

Using conducting probe atomic force microscopy (CAFM), we show that electrical conductivity in oligothiophene molecular films deposited on SiO(2)/Si wafers is extremely sensitive to degree of crystalline order in the film. By locally distorting the molecular order in the films through the controlled application of pressure with the AFM tip, the lateral charge transport was reduced by factors varying from 2 to 10, even when no changes in the height of the film could be observed.

3.
Nano Lett ; 12(3): 1295-9, 2012 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-22339758

RESUMO

Transmission electron microscopy was used to determine the structure of molecular films of self-assembled monolayers of pentathiophene derivatives supported on various electron transparent substrates. Despite the extreme beam sensitivity of the monolayers, structural crystallographic maps were obtained that revealed the nanoscale structure of the film. The image resolution is determined by the minimum beam diameter that the radiation hardness of the monolayer can support, which in our case is about 90 nm for a beam current of 5 × 10(6) e(-)/s. Electron diffraction patterns were collected while scanning a parallel electron beam over the film. These maps contain uncompromised information of the size, symmetry and orientation of the unit cell, orientation and structure of the domains, degree of crystallinity, and their variation on the micrometer scale, which are crucial to understand the electrical transport properties of the organic films. This information allowed us to track small changes in the unit cell size driven by the chemical modification of the support film.


Assuntos
Membranas Artificiais , Microscopia Eletrônica/métodos , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Compostos Orgânicos/química , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Tamanho da Partícula , Propriedades de Superfície
4.
Nano Lett ; 11(10): 4107-12, 2011 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-21848283

RESUMO

Using conducting probe atomic force microscopy (CAFM) we have investigated the electrical conduction properties of monolayer films of a pentathiophene derivative on a SiO(2)/Si-p+ substrate. By a combination of current-voltage spectroscopy and current imaging we show that lateral charge transport takes place in the plane of the monolayer via hole injection into the highest occupied molecular orbitals of the pentathiophene unit. Our CAFM data suggest that the conductivity is anisotropic relative to the crystalline directions of the molecular lattice.

5.
PLoS One ; 6(2): e16894, 2011 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-21326867

RESUMO

BACKGROUND: Mice irradiated and reconstituted with hematopoietic cells lacking manganese superoxide dismutase (SOD2) show a persistent hemolytic anemia similar to human sideroblastic anemia (SA), including characteristic intra-mitochondrial iron deposition. SA is primarily an acquired, clonal marrow disorder occurring in individuals over 60 years of age with uncertain etiology. METHODOLOGY/PRINCIPAL FINDINGS: To define early events in the pathogenesis of this murine model of SA, we compared erythroid differentiation of Sod2⁻/⁻ and normal bone marrow cells using flow cytometry and gene expression profiling of erythroblasts. The predominant transcriptional differences observed include widespread down-regulation of mitochondrial metabolic pathways and mitochondrial biogenesis. Multiple nuclear encoded subunits of complexes I-IV of the electron transport chain, ATP synthase (complex V), TCA cycle and mitochondrial ribosomal proteins were coordinately down-regulated in Sod2⁻/⁻ erythroblasts. Despite iron accumulation within mitochondria, we found increased expression of transferrin receptor, Tfrc, at both the transcript and protein level in SOD2 deficient cells, suggesting deregulation of iron delivery. Interestingly, there was decreased expression of ABCb7, the gene responsible for X-linked hereditary SA with ataxia, a component required for iron-sulfur cluster biogenesis. CONCLUSIONS/SIGNIFICANCE: These results indicate that in erythroblasts, mitochondrial oxidative stress reduces expression of multiple nuclear genes encoding components of the respiratory chain, TCA cycle and mitochondrial protein synthesis. An additional target of particular relevance for SA is iron:sulfur cluster biosynthesis. By decreasing transcription of components of cluster synthesis machinery, both iron utilization and regulation of iron uptake are impacted, contributing to the sideroblastic phenotype.


Assuntos
Células Eritroides/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/fisiologia , Receptores da Transferrina/genética , Superóxido Dismutase/genética , Anemia Sideroblástica/genética , Anemia Sideroblástica/metabolismo , Anemia Sideroblástica/patologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Eritroblastos/metabolismo , Eritroblastos/fisiologia , Feminino , Regulação da Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/genética , Receptores da Transferrina/metabolismo , Superóxido Dismutase/metabolismo , Regulação para Cima
6.
Rev Sci Instrum ; 82(12): 123901, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22225225

RESUMO

Reliable measurement of electrical charge transport in molecular layers is a delicate task that requires establishing contacts with electrodes without perturbing the molecular structure of the film. We show how this can be achieved by means of novel device consisting of ultra-flat electrodes separated by insulating material to support the molecular film. We show the fabrication process of these electrodes using a replica technique where gold electrodes are embedded in a silicon oxide film deposited on the angstrom-level flat surface of a silicon wafer. Importantly, the co-planarity of the electrode and oxide areas of the substrate was in the sub-nanometer range. We illustrate the capabilities of the system by mapping the distribution of electrical transport pathways in molecular thin films of self-assembled oligothiophene derivatives using conductive atomic force microscopy. In comparison with traditional bottom contact non-coplanar electrodes, the films deposited on our electrodes exhibited contact resistances lower by a factor of 40 than that of the similar but non-coplanar electrodes.

7.
Chem Commun (Camb) ; 46(45): 8579-81, 2010 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-20972497

RESUMO

Symmetrically substituted hexakis(alkoxy)triphenylene (HAT) derivatives were assembled into single molecular thick 2D nanosheets, which stacked further to give multilayered nanofibers through a convenient solution process. Detailed information on molecular arrangement was unraveled by various imaging techniques and diffraction studies.

8.
Blood Cells Mol Dis ; 45(3): 227-32, 2010 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-20800516

RESUMO

The antioxidant enzyme manganese superoxide dismutase (SOD2) serves as the primary defense against mitochondrial superoxide. Impaired SOD2 activity in murine hematopoietic cells affects erythroid development, resulting in anemia characterized by intra-mitochondrial iron deposition, reticulocytosis and shortened red cell life span. Gene expression profiling of normal and SOD2 deficient erythroblasts identified the Parkinson's disease locus DJ-1 (Park7) as a differentially expressed transcript. To investigate the role of DJ-1 in hematopoietic cell development and protection against oxidative stress caused by Sod2 loss, we evaluated red cell parameters, reticulocyte count, red cell turnover and reactive oxygen species production in DJ-1 knockout animals and chimeric animals lacking both SOD2 and DJ-1 in hematopoietic cells generated by fetal liver transplantation. We also investigated DJ-1 protein expression in primary murine erythroid and erythroleukemia cells (MEL). Loss of DJ-1 exacerbates the phenotype of SOD2 deficiency, increasing reticulocyte count and decreasing red cell survival. Using MEL cells, we show that DJ-1 is up-regulated at the protein level during erythroid differentiation. These results indicate that DJ-1 plays a physiologic role in protection of erythroid cells from oxidant damage, a function unmasked in the context of oxidative stress.


Assuntos
Eritrócitos/metabolismo , Células Precursoras Eritroides/metabolismo , Proteínas Oncogênicas/biossíntese , Estresse Oxidativo/fisiologia , Superóxido Dismutase/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Perfilação da Expressão Gênica , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Oncogênicas/genética , Peroxirredoxinas , Proteína Desglicase DJ-1 , Superóxido Dismutase/genética , Superóxidos/metabolismo , Regulação para Cima/fisiologia
10.
Free Radic Biol Med ; 44(6): 1088-96, 2008 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-18206125

RESUMO

Free cysteamine levels in mouse tissues have been strictly correlated to the presence of membrane-bound pantetheinase activity encoded by Vanin-1. Vanin-1 is involved in many biological processes in mouse, from thymus homing to sexual development. Vanin-1 -/- mice are fertile and grow and develop normally; they better control inflammation and most of the knockout effects were rescued by cystamine treatment. Gene structure analysis showed the presence of an oxidative stimuli-responsive ARE-like sequence in the promoter. In this paper we investigate antioxidant-detoxifying enzymatic activities at the tissue level, comparing Vanin-1 -/- and wild-type mice. In Vanin-1 null animals we pointed out a decrease in the Se-independent glutathione peroxidase activity. The decrease in enzymatic activity appeared to be correlated to an impairment of GST isoenzyme levels. In particular a significant drop in GSTA3 together with a minor decrement in GSTM1 and an increase in GSTP1 levels was detected in Vanin-1 -/- livers. Cystamine administration to Vanin-1 -/- mice restored specifically GSTA3 levels and the corresponding enzymatic activity without influencing protein expression. A possible role of cystamine on protein stability/folding can be postulated.


Assuntos
Antioxidantes/metabolismo , Moléculas de Adesão Celular/genética , Cistamina/farmacologia , Glutationa Transferase/metabolismo , Protetores contra Radiação/farmacologia , Amidoidrolases , Animais , Western Blotting , Catalase/metabolismo , Cromatografia Líquida de Alta Pressão , Eletroforese em Gel de Poliacrilamida , Proteínas Ligadas por GPI , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Isoenzimas/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Superóxido Dismutase/metabolismo
11.
J Exp Med ; 203(13): 2817-27, 2006 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-17145956

RESUMO

Colitis involves immune cell-mediated tissue injuries, but the contribution of epithelial cells remains largely unclear. Vanin-1 is an epithelial ectoenzyme with a pantetheinase activity that provides cysteamine/cystamine to tissue. Using the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-colitis model we show here that Vanin-1 deficiency protects from colitis. This protection is reversible by administration of cystamine or bisphenol A diglycidyl ether, a peroxisome proliferator-activated receptor (PPAR)gamma antagonist. We further demonstrate that Vanin-1, by antagonizing PPARgamma, licenses the production of inflammatory mediators by intestinal epithelial cells. We propose that Vanin-1 is an epithelial sensor of stress that exerts a dominant control over innate immune responses in tissue. Thus, the Vanin-1/pantetheinase activity might be a new target for therapeutic intervention in inflammatory bowel disease.


Assuntos
Moléculas de Adesão Celular/fisiologia , Colite/metabolismo , Células Epiteliais/metabolismo , PPAR gama/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/fisiologia , Amidoidrolases , Animais , Compostos Benzidrílicos , Peso Corporal , Moléculas de Adesão Celular/deficiência , Moléculas de Adesão Celular/genética , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CXCL2 , Quimiocinas/genética , Quimiocinas/metabolismo , Colite/induzido quimicamente , Colite/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Ciclo-Oxigenase 2/metabolismo , Cistamina/farmacologia , Citocinas/genética , Citocinas/metabolismo , Células Epiteliais/efeitos dos fármacos , Compostos de Epóxi/farmacologia , Proteínas Ligadas por GPI , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-1beta/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Camundongos SCID , PPAR gama/antagonistas & inibidores , PPAR gama/genética , Prostaglandina D2/análogos & derivados , Prostaglandina D2/farmacologia , Análise de Sobrevida , Ácido Trinitrobenzenossulfônico
12.
Antioxid Redox Signal ; 8(7-8): 1217-25, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16910769

RESUMO

Iron overload is a feature of an array of human disorders such as sideroblastic anemias, a heterogeneous group of erythropoietic disorders without identified cause in most cases. However, sideroblastic anemias appear to result from a disturbance at the interface between mitochondrial function and iron metabolism. A defining feature is excessive iron deposition within mitochondria of developing red cells, the consequences of which are an increase in cellular free radicals production, increased damage to proteins, and reduced cell survival. Because of its mitochondrial location, superoxide dismutase (SOD2) is the principal defense against the toxicity of superoxide anions generated by the oxidative phosphorylation. We have used hematopoietic stem cell transplantation to study blood cells lacking SOD2. We became interested in the role SOD2 plays in the metabolism of superoxide anions during erythroid development, as anemia is the major phenotype in transplanted animals. Our exploration of this model suggests that oxidative stress-and in particular, mitochondrial- derived oxidants-plays an important role in the pathogenesis of the human disorder, sideroblastic anemia. Here we review the relation between mitochondrial dysfunction and sideroblastic anemia, describe several methods for assessing oxidative damage to mature or developing red cells, present data on, and discuss the potential of antioxidant therapy for this disorder.


Assuntos
Anemia Sideroblástica/metabolismo , Anemia Sideroblástica/patologia , Antioxidantes/metabolismo , Estresse Oxidativo , Superóxido Dismutase/deficiência , Anemia Sideroblástica/enzimologia , Anemia Sideroblástica/etiologia , Anemia Sideroblástica/genética , Animais , Antioxidantes/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Eritrócitos/patologia , Humanos , Manganês/administração & dosagem , Manganês/uso terapêutico , Manganês/toxicidade , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxidos/metabolismo
13.
Exp Hematol ; 33(12): 1493-9, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16338492

RESUMO

OBJECTIVE: Iron overload is a key contributor to the pathogenesis of multiple disorders including the sideroblastic anemias. The specific iron compounds present in tissues or cells that are the target of iron deposition remain poorly understood, but there is evidence that some forms are magnetically active. We have developed a simple and specific method to purify iron-overloaded red blood cells using magnetic affinity columns. Here we describe this method and characterize purified Sod2-deficient siderocytes. MATERIALS AND METHODS: RBC derived from mice transplanted with Sod2-deficient hematopoietic stem cells served as a source of iron-laden cells. Purification was based upon the observation that iron deposits in Sod2-deficient cells are "magnetically susceptible" and allow for retention of iron-laden cells in a strong magnetic field. Peripheral blood from Sod2-deficient chimeric mice was passed through magnetic separation columns; iron-overloaded cells were eluted and characterized by flow cytometry, Western blot, and microscopy. RESULTS: We were able to purify 2.8% of the total red cells as iron-laden siderocytes. The magnetically purified Sod2-deficient cells were predominantly identified as reticulocytes. They had numerous siderotic granules, produced enhanced levels of reactive oxygen species, and showed increased protein oxidative damage, mitochondrial enrichment, and mitochondrial hyperpolarization. CONCLUSIONS: Our method can be used to purify iron-laden cells as well as iron-associated subcellular fractions prepared from iron-loaded tissues, allowing elucidation of the structure, location, and protein composition of such iron deposits. This data will help develop our understanding of the pathogenesis of SA and other disorders characterized by iron overload.


Assuntos
Anemia Sideroblástica/sangue , Eritrócitos/patologia , Separação Imunomagnética/métodos , Sobrecarga de Ferro/sangue , Animais , Cromatografia de Afinidade , Ferro/metabolismo , Métodos , Camundongos , Mitocôndrias/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/deficiência
14.
Sci Aging Knowledge Environ ; 2004(32): pe32, 2004 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-15308771

RESUMO

Circumstantial evidence places the p66 isoform of the adapter protein Shc in a position to mediate the accelerated aging phenotype displayed by mice expressing shortened forms of the tumor suppressor protein p53. We present a model in which p66(shc) may be responsible for integrating signals from the p53 pathway with signals from the insulin-like growth factor-1/Daf pathway in mammals. A full understanding of how interactions between p53 and p66(shc) affect longevity will require the production of animals with mutations in the genes encoding both proteins.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas Adaptadoras de Transporte Vesicular/fisiologia , Envelhecimento/fisiologia , Proteínas Adaptadoras de Transporte Vesicular/deficiência , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Envelhecimento/genética , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/fisiologia , Longevidade/genética , Camundongos , Receptor IGF Tipo 1/metabolismo , Receptor IGF Tipo 1/fisiologia , Proteínas Adaptadoras da Sinalização Shc , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/fisiologia
15.
Blood ; 104(8): 2565-73, 2004 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-15205258

RESUMO

SOD2 is an antioxidant protein that protects cells against mitochondrial superoxide. Hematopoietic stem cells (HSCs) lacking SOD2 are capable of rescuing lethally irradiated hosts, but reconstituted animals display a persistent hemolytic anemia characterized by increased oxidative damage to red cells, with morphologic similarity to human "sideroblastic" anemia. We report further characterization of this novel SOD2-deficiency anemia. Electron micrographs of SOD2-deficient reticulocytes reveal striking mitochondrial proliferation and mitochondrial membrane thickening. Peripheral blood smears show abundant iron-stainable granules in mature red cells (siderocytes). Fluorescence-activated cell sorting (FACS) analysis of cells labeled with oxidation-sensitive dyes demonstrates enhanced production of superoxide and hydrogen peroxide by SOD2-deficient cells. Oxidative damage to proteins is increased in SOD2-deficient cells, with much of the damage affecting membrane/insoluble proteins. Red cell proteome analysis demonstrates that several proteins involved in folding/chaperone function, redox regulation, adenosine triphosphate (ATP) synthesis, and red cell metabolism show altered expression in SOD2-deficient cells. This data, combined with information on how protein expression levels change upon antioxidant therapy, will aid in identification of proteins that are sensitive to oxidative damage in this model, and by extension, may have a role in the regulation of red cell lifespan in other hemolytic disorders.


Assuntos
Anemia/metabolismo , Anemia/patologia , Antioxidantes/metabolismo , Regulação da Expressão Gênica , Estresse Oxidativo , Superóxido Dismutase/deficiência , Trifosfato de Adenosina/metabolismo , Anemia/enzimologia , Anemia/genética , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Medula Óssea/metabolismo , Medula Óssea/patologia , Catálise , Cloretos/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Eritrócitos/patologia , Eritropoese , Peróxido de Hidrogênio/metabolismo , Transporte de Íons , Ferro/metabolismo , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Oxirredução , Potássio/metabolismo , Proteômica , Protoporfirinas/metabolismo , Baço/metabolismo , Baço/patologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxidos/metabolismo
16.
J Clin Invest ; 113(4): 591-7, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14966568

RESUMO

Vanin-1 is a membrane-anchored pantetheinase highly expressed in the gut and liver. It hydrolyzes pantetheine to pantothenic acid (vitamin B5) and the low-molecular-weight thiol cysteamine. The latter is believed to be a key regulating factor of several essential metabolic pathways, acting through sulfhydryl-disulfide exchange reactions between sulfhydryl groups of the enzymes and the oxidized form, cystamine. Its physiological importance remains to be elucidated, however. To explore this point, we developed Vanin-1-deficient mice that lack free cysteamine. We examined the susceptibility of deficient mice to intestinal inflammation, either acute (NSAID administration) or chronic (Schistosoma infection). We found that Vanin-1(-/-) mice better controlled inflammatory reaction and intestinal injury in both experiments. This protection was associated with increased gamma-glutamylcysteine synthetase activity and increased stores of reduced glutathione, as well as reduced inflammatory cell activation in inflamed tissues. Oral administration of cystamine reversed all aspects of the deficient phenotype. These findings suggest that one cysteamine function is to upregulate inflammation. Consequently, the pantetheinase activity of Vanin-1 molecule could be a target for a new anti-inflammatory strategy.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Moléculas de Adesão Celular/metabolismo , Glutationa/metabolismo , Indometacina/toxicidade , Inflamação/patologia , Intestinos/patologia , Schistosoma mansoni/metabolismo , Esquistossomose mansoni/patologia , Amidoidrolases , Animais , Moléculas de Adesão Celular/genética , Quimiocina CXCL2 , Quimiocinas/genética , Quimiocinas/metabolismo , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Cisteamina/metabolismo , Proteínas Ligadas por GPI , Glutamato-Cisteína Ligase/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/citologia , Intestinos/parasitologia , Isoenzimas/genética , Isoenzimas/metabolismo , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandina-Endoperóxido Sintases/metabolismo , Esquistossomose mansoni/metabolismo , Taxa de Sobrevida
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