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1.
Oxid Med Cell Longev ; 2020: 3721383, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184915

RESUMO

Intraplaque hemorrhage frequently occurs in atherosclerotic plaques resulting in cell-free hemoglobin, which is oxidized to ferryl hemoglobin (FHb) in the highly oxidative environment. Osteoclast-like cells (OLCs) derived from macrophages signify a counterbalance mechanism for calcium deposition in atherosclerosis. Our aim was to investigate whether oxidized hemoglobin alters osteoclast formation, thereby affecting calcium removal from mineralized atherosclerotic lesions. RANKL- (receptor activator of nuclear factor kappa-Β ligand-) induced osteoclastogenic differentiation and osteoclast activity of RAW264.7 cells were studied in response to oxidized hemoglobin via assessing bone resorption activity, expression of osteoclast-specific genes, and the activation of signalization pathways. OLCs in diseased human carotid arteries were assessed by immunohistochemistry. FHb, but not ferrohemoglobin, decreased bone resorption activity and inhibited osteoclast-specific gene expression (tartrate-resistant acid phosphatase, calcitonin receptor, and dendritic cell-specific transmembrane protein) induced by RANKL. In addition, FHb inhibited osteoclastogenic signaling pathways downstream of RANK (receptor activator of nuclear factor kappa-Β). It prevented the induction of TRAF6 (tumor necrosis factor (TNF) receptor-associated factor 6) and c-Fos, phosphorylation of p-38 and JNK (c-Jun N-terminal kinase), and nuclear translocation of NFκB (nuclear factor kappa-Β) and NFATc1 (nuclear factor of activated T-cells, cytoplasmic 1). These effects were independent of heme oxygenase-1 demonstrated by knocking down HO-1 gene in RAW264.7 cells and in mice. Importantly, FHb competed with RANK for RANKL binding suggesting possible mechanisms by which FHb impairs osteoclastic differentiation. In diseased human carotid arteries, OLCs were abundantly present in calcified plaques and colocalized with regions of calcium deposition, while the number of these cells were lower in hemorrhagic lesions exhibiting accumulation of FHb despite calcium deposition. We conclude that FHb inhibits RANKL-induced osteoclastic differentiation of macrophages and suggest that accumulation of FHb in a calcified area of atherosclerotic lesion with hemorrhage retards the formation of OLCs potentially impairing calcium resorption.

2.
Oxid Med Cell Longev ; 2018: 3812568, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29560080

RESUMO

The infiltration of red blood cells into atheromatous plaques is implicated in atherogenesis. Inside the lesion, hemoglobin (Hb) is oxidized to ferri- and ferrylHb which exhibit prooxidant and proinflammatory activities. Cystathione gamma-lyase- (CSE-) derived H2S has been suggested to possess various antiatherogenic actions. Expression of CSE was upregulated predominantly in macrophages, foam cells, and myofibroblasts of human atherosclerotic lesions derived from carotid artery specimens of patients. A similar pattern was observed in aortic lesions of apolipoprotein E-deficient mice on high-fat diet. We identified several triggers for inducing CSE expression in macrophages and vascular smooth muscle cells including heme, ferrylHb, plaque lipids, oxidized low-density lipoprotein, tumor necrosis factor-α, and interleukin-1ß. In the interplay between hemoglobin and atheroma lipids, H2S significantly mitigated oxidation of Hb preventing the formation of ferrylHb derivatives, therefore providing a novel function as a heme-redox-intermediate-scavenging antioxidant. By inhibiting Hb-lipid interactions, sulfide lowered oxidized Hb-mediated induction of adhesion molecules in endothelium and disruption of endothelial integrity. Exogenous H2S inhibited heme and Hb-mediated lipid oxidation of human atheroma-derived lipid and human complicated lesion. Our study suggests that the CSE/H2S system represents an atheroprotective pathway for removing or limiting the formation of oxidized Hb and lipid derivatives in the atherosclerotic plaque.


Assuntos
Aterosclerose/sangue , Aterosclerose/tratamento farmacológico , Hemoglobinas/metabolismo , Sulfeto de Hidrogênio/farmacologia , Lipídeos/sangue , Placa Aterosclerótica/sangue , Placa Aterosclerótica/tratamento farmacológico , Animais , Aterosclerose/patologia , Células Cultivadas , Células Endoteliais , Humanos , Sulfeto de Hidrogênio/química , Camundongos , Camundongos Endogâmicos C57BL , Morfolinas/química , Morfolinas/farmacologia , Compostos Organofosforados/química , Compostos Organofosforados/farmacologia , Compostos Organotiofosforados/química , Compostos Organotiofosforados/farmacologia , Piperidinas/química , Piperidinas/farmacologia , Placa Aterosclerótica/patologia , Pirrolidinas/química , Pirrolidinas/farmacologia
3.
Cytometry B Clin Cytom ; 94(2): 363-368, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-27792269

RESUMO

BACKGROUND: Bronchoalveolar mesenchymal stem cells (MSCs) play an important role in the maintenance of lung integrity. Therapeutic application of bone marrow-derived MSCs reduced chronic bronchial inflammation in idiopathic pulmonary fibrosis, and improved the ratio of survivors in sepsis with pneumonia. This study investigated the effect of MSCs from bronchoalveolar lavage fluid (BALF) of hypersensitivity pneumonitis (HP) on T-cell function under in vitro conditions. METHODS: Bronchoalveolar MSCs were obtained via bronchoscopy with BAL from children with severe subacute HP. As control, BALF MSCs were assessed from children without any inflammatory lung disease. Isolated MSCs were characterized via immunophenotyping by flow cytometry and confocal laser scanning microscopy. HP-derived and healthy separated peripheral blood mononuclear cells (PBMCs) were stimulated by 5 µg/mL phytohemagglutinin in the presence of HP-derived or control MSCs in 5-day cultures. Proliferation and activation of T-cells were characterized by the mean fluorescence intensity (MFI) of 5,6-carboxyfluorescein-diacetat succinimidyl ester (CFSE) and CD25, CD69 as well as HLA-DR surface positivities, respectively. RESULTS: HP-derived MSCs showed significantly lower level of CD73, CD90, and CD105 expression compared to control MSCs in both flow cytometric and confocal microscopic experiments. MSCs from HP did not reduce T-cell proliferation based on CFSE MFI values, while the level of CD25 expression on both control and HP-derived CD4+ and CD8+ T-cells was significantly reduced by normal MSCs, while HP-derived MSCs did not have any significant effect. The level of other activation markers was not markedly modulated by MSCs. CONCLUSIONS: BALF MSCs from HP are unable to downregulate the proliferation and activation of T-cells that may support the development of recurrent intrapulmonary inflammation in HP. © 2016 International Clinical Cytometry Society.


Assuntos
Alveolite Alérgica Extrínseca/patologia , Líquido da Lavagem Broncoalveolar/citologia , Células-Tronco Mesenquimais/patologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Proliferação de Células/fisiologia , Criança , Feminino , Citometria de Fluxo/métodos , Humanos , Imunofenotipagem/métodos , Inflamação/patologia , Masculino
4.
Pathol Oncol Res ; 18(1): 43-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21667346

RESUMO

The addition of rituximab to conventional chemotherapy has significantly improved the treatment outcome in diffuse large B-cell lymphoma. However, differences in treatment response and survival data can be observed independently from the International Prognostic Index scores. The current study evaluated the impact of Fc-gamma-receptor IIIa polymorphism and gene expression profile on the response of DLBCL patients to R-CHOP therapy as well as on their survival results. Fifty-one patients were involved, thirty-two females, nineteen males, their median age was 53.1 years. The FCGR3A polymorphism at the 158. amino acid position determined with PCR method showed the following results: VV: 12 cases (23.5%), VF: 29 cases (56.8%) and FF: 10 cases (19.6%), respectively. There was no significant difference between the treatment responses of the three groups. The event-free survival data were less favorable in the F-allele carriers than in V/V homozygous patients, but without any significancy, and the overall survival curves were almost the same. As for the gene expression profile, 20 patients' biopsy specimens showed germinal center and 31 showed non-germinal center characteristics. Treatment results did not differ from each other in the two groups. Both the event-free and the overall survival data were more favorable in the GC group, however the differences were not significant. Our results contest the predictive value of Fc-gamma-receptor IIIa polymorphism and gene expression profile in diffuse large B-cell lymphoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Receptores de IgG/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Perfilação da Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prednisona/administração & dosagem , Prognóstico , Rituximab , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem
6.
Clin Rheumatol ; 29(7): 811-4, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20221841

RESUMO

The idiopathic inflammatory myopathies are systemic autoimmune diseases characterized by chronic inflammation, resulting in the progressive weakness of the proximal muscles. Myositis-specific or myositis-associated autoantibodies can often be found in serum of polymyositis and dermatomyositis patients. This autoantibody presence may play a significant role in patient diagnosis and classification. We present a female polymyositis patient characterized with serious muscle weakness and lung involvement. Anti-Jo1 antibodies were detected in the patient's serum at the time of diagnosis. After 5 years of treatment and surveillance, recent laboratory analysis showed the presence anti-SRP antibody in her serum.


Assuntos
Autoanticorpos/sangue , Polimiosite , Partícula de Reconhecimento de Sinal , Idoso , Feminino , Humanos , Polimiosite/sangue , Polimiosite/diagnóstico , Polimiosite/imunologia , Aminoacil-RNA de Transferência , Partícula de Reconhecimento de Sinal/imunologia
7.
Rheumatology (Oxford) ; 49(1): 25-33, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19920092

RESUMO

OBJECTIVE: HLA-DR [shared epitope (SE)] alleles have recently been re-classified into S1, S2, S3P and S3D groups. S2 and S3P have been associated with increased risk for RA. We assessed the impact of S1, S2, S3P and S3D alleles on anti-citrullinated protein antibody (ACPA) production. Instead of comparing allele-carriers to non-carriers, we studied each allele group individually, using the X/X (non-SE) genotype as reference. METHODS: Serum and genomic DNA samples of 91 RA patients and 78 healthy controls were obtained. Various ACPAs and IgM RF were determined by ELISA. HLA-DRB1 genotyping and subtyping was performed by PCR. HLA-DRB1 alleles were re-classified as described above. Correlations between SE and ACPAs were determined. RESULTS: Not only S2 and S3P, but, to a lesser extent, S1 and S3D alleles also predisposed to anti-cyclic citrullinated peptide (CCP) production (P < 0.0001, P = 0.004, P = 0.01 and P = 0.027, respectively), with the following hierarchy of association: S2+S3P > S1+S3D > X/X. Similar associations were observed for anti-citrullinated vimentin. Anti-citrullinated fibrinogen (CF) exerted a different association pattern with the strongest correlation with S1 alleles [odds ratio (OR) 16.00; P = 0.05]. In addition, HLA-DRB1*15 alleles may represent a special predisposing effect for anti-CF antibody production. Finally, in this study, RF production was associated only with the HLA-DRB1*0401 SE allele (P = 0.04). CONCLUSIONS: Our approach of comparing individual S allele carriers with X/X genotype patients allowed us to perform unequivocal analyses and demonstrate new associations. Thus, novel subgroups of RA could be identified with potential relevance for prognosis and therapy.


Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/biossíntese , Epitopos/imunologia , Antígenos HLA-DR/genética , Peptídeos Cíclicos/imunologia , Adulto , Idoso , Artrite Reumatoide/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Antígenos HLA-DR/imunologia , Cadeias HLA-DRB1 , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Fator Reumatoide/análise , Fatores de Risco
8.
Autoimmun Rev ; 9(3): 140-3, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19427413

RESUMO

Anti-citrullinated protein/peptide antibodies (ACPA) have recently emerged as sensitive and specific serological markers of rheumatoid arthritis (RA), providing superior alternative of the rheumatoid factor (RF) test in the laboratory diagnostics of RA. Citrullination is a post-translational modification of arginine by deimination, physiologically occurring during apoptosis, inflammation or keratinization. The presence of several citrullinated proteins has been demonstrated in the RA synovium. The identification of citrullinated epitopes as targets led to the development of the first and later second-generation anti-cyclic citrullinated peptide (anti-CCP) antibody assays. The anti-Sa antibody has been identified a decade ago; however, recent studies confirmed that anti-Sa is directed against citrullinated vimentin. The determination of ACPA may have important prognostic significance, since ACPA production can precede the onset of clinical RA symptoms by years. ACPA(+) individuals with early, undifferentiated arthritis may have higher risk to develop RA. ACPA has important prognostic role during the progression of RA and it has also been associated with pronounced radiographic progression. ACPA production has been associated with several genetic predisposing factors, including HLA-DRB1 and PTPN22 1858T alleles, as well as with environmental and lifestyle-related factors, primarily smoking and possibly, the use of oral contraceptives and excessive caffeine intake. Thus, the assessment of ACPA, in addition to clinical, radiographic and genetic outcome measures may be important to assess disease prognosis and aids to design effective, early therapeutic strategies.


Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Citrulina/imunologia , Testes Genéticos , Animais , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/genética , Artrite Reumatoide/terapia , Autoanticorpos/sangue , Humanos , Peptídeos/imunologia , Prognóstico
9.
Ann N Y Acad Sci ; 1173: 545-51, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19758197

RESUMO

We investigated the genetic background regarding major histocompatibility complex (MHC) II alleles in patients with systemic lupus erythematosus (SLE) only, in patients with SLE with secondary antiphospholipid syndrome (SLE+SAPS), and in patients whose clinical course began as primary antiphospholipid syndrome (PAPS) and subsequently progressed to SLE (PAPS+SLE) in order to explain the phenotypical differences found in our previous study. Those with primary or secondary APS present more thrombotic and less inflammatory activity. Fetal wastage was the highest in the PAPS+SLE group. We performed human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 genotyping in 63 patients (26, 22, and 15 in SLE only, SLE+SAPS, and PAPS+SLE groups, respectively) and in 57 healthy controls, using PCR with sequence-specific primers. We found that, as reported in the literature, the occurrence of DRB1*03 and DQB1*0201 alleles was higher in SLE patients than in controls, but these alleles were rare in the PAPS+SLE group (13% in PAPS+SLE vs. 46% in the SLE only group; P = 0.044). HLA-DRB1*04 alleles were expressed frequently in both primary and secondary APS. DRB1*13, DQB1*06, and DQB1*0302 alleles were present more frequently in the PAPS+SLE patients than in the other groups, while the DQB1*0301 allele was rare. In this study we have shown that the SLE-associated DRB1*03/DQB1*02 alleles occurred frequently in our lupus patients as well as in SLE patients with secondary APS. In patients who started as PAPS and later progressed to SLE, the allele frequency was fundamentally different. Taken together, our results confirmed that the HLA-DRB1 and HLA-DQB1 profile of PAPS and SAPS is different. Therefore it is unlikely that these alleles are responsible for the partly similar phenotype of the two groups.


Assuntos
Síndrome Antifosfolipídica/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Lúpus Eritematoso Sistêmico/genética , Alelos , Anticorpos Anticardiolipina/sangue , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Autoanticorpos/sangue , Feminino , Frequência do Gene , Genótipo , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Estudos Retrospectivos , beta 2-Glicoproteína I/imunologia
10.
Rheumatol Int ; 29(7): 793-6, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19034456

RESUMO

The C1858T allele of the PTPN22 gene has been reported to confer risk for RA; but in some reports, the effect was restricted to RF- and/or anti-CCP-seropositive patients. Hungarian RA patients and matched controls were genotyped. The 1858T allele showed an increased prevalence in RA patients compared to controls. The 1858T allele represents a risk factor in the whole RA population (P = 0.001); an association was found both in RF-seropositive (P = 0.001) and anti-CCP-seropositive patients (P = 0.001), and in subjects with the combination of these factors (P = 0.002). In TT homozygotes, the estimated susceptibility to RA was more than double (OR = 5.04) of that seen in TC heterozygotes (OR = 1.89); the same gene dosage effect was observed in all seropositive RA subgroups. Our data show that the Hungarian RA patients belong to the populations in which the 1858T allele represents a susceptibility factor both in the RF- and/or anti-CCP-seropositive subjects, and the association exhibit a gene dosage dependency.


Assuntos
Artrite Reumatoide/enzimologia , Artrite Reumatoide/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Adulto , Distribuição por Idade , Idoso , Artrite Reumatoide/etnologia , Análise Mutacional de DNA , Feminino , Dosagem de Genes/genética , Frequência do Gene/genética , Marcadores Genéticos/genética , Testes Genéticos , Genótipo , Homozigoto , Humanos , Hungria/etnologia , Ativação Linfocitária/genética , Masculino , Pessoa de Meia-Idade , Fator Reumatoide/genética , Distribuição por Sexo , Linfócitos T/enzimologia
11.
J Basic Microbiol ; 48(6): 480-7, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18785661

RESUMO

tert -Butylhydroperoxide (t BOOH) tolerant Candida albicans mutants developed from clinical isolates were characterized with increased tolerance of the oxidative stress generating agents t BOOH and H2O2, continuous induction of the antioxidative defence system, reduced pseudohypha and hypha-forming capabilities, decreased phospholipase secretion and delayed growth in Sabouraud dextrose agar and broth media. Changes in antimycotic (fluconazole, voriconazole, amphotericin B, 5-fluorocytosine) tolerances as well as in total and cytochrome c-dependent respirations showed versatile patterns, meanwhile the intensified alternative oxidase-dependent respiration of the mutants indicated that this respiratory pathway was an important element of the antioxidative defence in general. Because the phenotypes of increased oxidative stress tolerance and reduced virulence attribute production always emerged concomitantly in t BOOH-tolerant mutants the natural selection of C. albicans strains more tolerant of oxidative stress is unlikely. Not surprisingly, a screening study failed to detect any C. albicans strains with increased oxidative stress tolerance among 46 randomly selected clinical isolates.


Assuntos
Candida albicans/fisiologia , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Mutação , terc-Butil Hidroperóxido/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/genética , DNA Fúngico/química , DNA Fúngico/isolamento & purificação , Peróxido de Hidrogênio/metabolismo , Hifas , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , terc-Butil Hidroperóxido/metabolismo
12.
Clin Chem ; 54(4): 697-704, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18258668

RESUMO

BACKGROUND: Haptoglobin (Hp) alpha-chain alleles 1 and 2 account for 3 phenotypes that may influence the course of inflammatory diseases via biologically important differences in their antioxidant, scavenging, and immunomodulatory properties. Hp1-1 genotype results in the production of small dimeric, Hp2-1 linear, and Hp2-2 cyclic polymeric haptoglobin molecules. We investigated the haptoglobin polymorphism in patients with celiac disease and its possible association to the presenting symptoms. METHODS: We studied 712 unrelated, biopsy-proven Hungarian celiac patients (357 children, 355 adults; severe malabsorption 32.9%, minor gastrointestinal symptoms 22.8%, iron deficiency anemia 9.4%, dermatitis herpetiformis 15.6%, silent disease 7.2%, other 12.1%) and 384 healthy subjects. We determined haptoglobin phenotypes by gel electrophoresis and assigned corresponding genotypes. RESULTS: Hp2-1 was associated with a significant risk for celiac disease (P = 0.0006, odds ratio [OR] 1.54, 95% CI 1.20-1.98; prevalence 56.9% in patients vs 46.1% in controls). It was also overrepresented among patients with mild symptoms (69.2%) or silent disease (72.5%). Hp2-2 was less frequent in patients than in controls (P = 0.0023), but patients having this phenotype were at an increased risk for severe malabsorption (OR 2.21, 95% CI 1.60-3.07) and accounted for 45.3% of all malabsorption cases. Celiac and dermatitis herpetiformis patients showed similar haptoglobin phenotype distributions. CONCLUSIONS: The haptoglobin polymorphism is associated with susceptibility to celiac disease and its clinical presentations. The predominant genotype in the celiac population was Hp2-1, but Hp2-2 predisposed to a more severe clinical course. The phenotype-dependent effect of haptoglobin may result from the molecule's structural and functional properties.


Assuntos
Doença Celíaca/genética , Haptoglobinas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Celíaca/fisiopatologia , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo Genético , Fatores de Risco
13.
FEMS Yeast Res ; 7(6): 834-47, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17498215

RESUMO

We tested the hypothesis that adaptation of Candida albicans to chronic oxidative stress inhibits the formation of hyphae and reduces pathogenicity. Candida albicans cells were exposed to increasing concentrations of t-butylhydroperoxide (tBOOH), a lipid peroxidation-accelerating agent, and mutants with heritable tBOOH tolerance were isolated. Hypha formation by the mutants was negligible on Spider agar, indicating that the development of oxidative stress tolerance prevented Candida cells from undergoing dimorphic switches. One of the mutants, C. albicans AF06, was five times less pathogenic in mice than its parental strain, due to its reduced germ tube-, pseudohypha- and hypha-forming capability, and decreased phospholipase secretion. An increased oxidative stress tolerance may therefore be disadvantageous when this pathogen leaves blood vessels and invades deep organs. The AF06 mutant was characterized by high intracellular concentrations of endogenous oxidants, reduced monounsaturated and polyunsaturated fatty acid contents, the continuous induction of the antioxidative defense system, decreased cytochrome c-dependent respiration, and increased alternative respiration. The mutation did not influence growth rate, cell size, cell surface, cellular ultrastructures, including mitochondria, or recognition by human polymorphonuclear leukocytes. The selection of oxidative stress-tolerant respiratory Candida mutants may also occur in vivo, when reduced respiration helps the fungus to cope with antimycotic agents.


Assuntos
Adaptação Fisiológica/fisiologia , Candida albicans/fisiologia , Candida albicans/patogenicidade , Mutação/genética , Estresse Oxidativo/fisiologia , terc-Butil Hidroperóxido/farmacologia , Adaptação Fisiológica/genética , Animais , Antifúngicos/farmacologia , Candida albicans/citologia , Candida albicans/efeitos dos fármacos , Candida albicans/genética , Candida albicans/crescimento & desenvolvimento , Tamanho Celular , DNA Fúngico/química , Regulação Fúngica da Expressão Gênica , Humanos , Hifas/crescimento & desenvolvimento , Peroxidação de Lipídeos/fisiologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fatores de Virulência/metabolismo
14.
FEMS Yeast Res ; 7(2): 265-75, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17266730

RESUMO

Although exposure of Candida albicans cells to high-dose (4 mM) methylprednisolone stimulated microbial growth, germination rate in serum and phospholipase release, it also promoted the recognition of C. albicans cells by polymorphonuclear leukocytes. Pretreatment of C. albicans cells with methylprednisolone did not result in any increase in the pathogenicity of the fungus in intraperitoneal and intravenous mouse assays. Therefore, the virulence of C. albicans is unlikely to increase in patients treated with comparably high-dose methylprednisolone on skin and mucosal membranes. Methylprednisolone treatments also increased the production of conjugated dienes and thiobarbituric acid-reactive substances, and the menadione sensitivity of C. albicans cells, which can be explained by a significant decrease in the specific activities of several antioxidant enzymes. The combination of methylprednisolone with oxidants, e.g. in topical applications, may be of clinical importance when the predisposition to candidiasis is high. Methylprednisolone treatments negatively affected membrane fluidity and decreased the antifungal effects of both the polyene antibiotic nystatin and the ergosterol biosynthesis inhibitor lovastatin, and also enhanced the deleterious effects of the polyene antimycotic amphotericin B on C. albicans cells. These corticosteroid-polyene drug interactions should be considered in the treatment of C. albicans infections in patients with prolonged topical application of corticosteroids.


Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade , Glucocorticoides/administração & dosagem , Metilprednisolona/administração & dosagem , Vitamina K 3/farmacologia , Vitaminas/farmacologia , Animais , Antioxidantes/metabolismo , Candida albicans/crescimento & desenvolvimento , Candida albicans/fisiologia , Candidíase/microbiologia , Permeabilidade da Membrana Celular , Interações de Medicamentos , Feminino , Glucocorticoides/farmacologia , Peroxidação de Lipídeos , Metilprednisolona/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Estresse Oxidativo , Virulência , Vitamina K 3/administração & dosagem , Vitaminas/administração & dosagem
15.
FEMS Yeast Res ; 6(8): 1140-8, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17156011

RESUMO

Lovastatin inhibited the growth of Candida albicans in a fungistatic way. Although it triggers apoptosis in a great variety of eukaryotic cells, including many tumour cell lines, lovastatin failed to provoke apoptotic events in this human pathogen. The fungistatic behaviour of this statin might arise from its negative influence on membrane fluidity. Because yeast-->pseudomycelium and hyphae morphogenetic transitions took place under exposure to lovastatin morphogenetic switch and apoptotic cell death must be regulated independently in C. albicans.


Assuntos
Antifúngicos/farmacologia , Apoptose/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Lovastatina/farmacologia , Candida albicans/crescimento & desenvolvimento , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Fragmentação do DNA/efeitos dos fármacos , DNA Fúngico/efeitos dos fármacos , Humanos
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