RESUMO
BACKGROUND: Serratia marcescens is a gram-negative bacterium that is widespread in the environment. S. marcescens bacteremia can be fatal during pregnancy and cause persistent chorioamnionitis. This study reports an outbreak of Serratia marcescens bloodstream infection (BSI) among high-risk pregnant women in an obstetric ward. The purpose of this study is to report our experience with the usefulness of the ATP test in hospital environmental management and to confirm that bloodstream infections of patients with the same strain were correlated by WGS testing. METHODS: This retrospective study collected the data of inpatients with S. marcescens bacteremia in obstetric ward for high-risk pregnant women from August 22, 2021, to October 14, 2021. We performed: an adenosine triphosphate (ATP) bioluminescence test in the environment with a high-contact area; environmental culture; on-site monitoring and staff education; and whole-genome sequencing (WGS) to evaluate genetic relationships among S. marcescens isolates. RESULTS: S. marcescens BSI occurred in four consecutive patients. None of the patients had central venous catheters. An ATP bioluminescence test revealed that high-contact areas and areas for injection preparation were not clean (≥ 1000 relative light units). However, S. marcescens was not identified in the environmental cultures, likely due to intensive environmental cleaning and discarding of potentially contaminated specimens before the culture test. On-site monitoring and education were conducted for 1 month. There were no further reports of BSI until 6 months after the last patient was discharged. WGS performed on three isolates from three patients indicated that the isolated S. marcescens was likely from the same strain. CONCLUSIONS: We controlled an S. marcescens outbreak by improving environmental cleaning as well as education of and behavior changes in healthcare workers. Using the ATP bioluminescence test can provide feedback on environmental cleaning and education. WGS played a role in determining the spread of BSI caused by the same strain.
Assuntos
Bacteriemia , Infecção Hospitalar , Sepse , Infecções por Serratia , Gravidez , Humanos , Feminino , Recém-Nascido , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Gestantes , Serratia marcescens/genética , Estudos Retrospectivos , Infecções por Serratia/epidemiologia , Infecções por Serratia/microbiologia , Sepse/epidemiologia , Surtos de Doenças , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Hospitais , Trifosfato de Adenosina , Unidades de Terapia Intensiva NeonatalRESUMO
BACKGROUND AND OBJECTIVES: Chemokines have various biological functions and potential roles in the development or progression of neuroinflammatory diseases. However, the specific pathogenic roles of chemokines in the major cause for vision loss among the elderly, the leading cause of blindness in older individuals, remain elusive. Chemokines interact with their receptors expressed in the endothelium and on leukocytes. The sulfation of tyrosine residues in chemokine receptors increases the strength of ligand-receptor interaction and modulates signaling. Therefore, in the present study, we aimed to construct a human recombinant sulfated CXCR3 peptide trap (hCXCR3-S2) and mouse recombinant sulfated CXCR3 peptide trap (mCXCR3-S2) to demonstrate in vivo effects in preventing choroidal neovascularization (CNV) and chemotaxis. MATERIALS AND METHODS: We generated expression vectors for mCXCR3-S2 and hCXCR3-S2 with GST domains and their respective cDNA sequences. Following overexpression in E. coli BL21 (DE3), we purified the fusion proteins from cell lysates using affinity chromatography. First, the impact of hCXCR3-S2 was validated in vitro. Subsequently, the in vivo efficacy of mCXCR3-S2 was investigated using a laser-induced CNV mouse model, a mouse model of neovascular age-related macular degeneration (AMD). RESULTS: hCXCR3-S2 inhibited the migration and invasion of two human cancer cell lines. Intravitreal injection of mCXCR3-S2 attenuated CNV and macrophage recruitment in neovascular lesions of mouse models. These in vitro and in vivo effects were significantly stronger with CXCR3-S2 than with wild-type CXCR3 peptides. CONCLUSION: These findings demonstrate that the sulfated form of the CXCR3 peptide trap is a valuable tool that could be supplemented with antivascular endothelial growth factors in AMD treatment.
RESUMO
Salmonella enterica serovar Typhimurium (hereafter referred to as Salmonella), a virulent pathogen, is known to induce hostcell death. Using reverse transcriptionquantitative polymerase chain reaction, a 28fold increase of microRNA (miR)155 expression in RAW 264.7 macrophages was observed following infection with Salmonella for 24 h. This miR155 upregulation increased macrophage cell death by up to 40% in 48 h following infection. Western blot analysis revealed that receptor interacting protein 1 (RIP1) and 3 (RIP3) were increased at 18 h following miR155 transfection to macrophages, similar to Salmonella infection. In addition, inhibition of RIP1 by preincubating macrophages with necrostatin1, a RIP1 specific inhibitor, increased the viability of Salmonellainfected cells and miR155transfected cells by up to 20%. The cleavage of poly (adenosine diphosphateribose) polymerase1 (PARP1) was also enhanced by miR155 induction upon Salmonella infection. Therefore, it was suggested that RIP1/3induced necroptosis and PARP1mediated necrosis caused by miR155 induction may represent distinct routes of programmed necrotic cell death of Salmonellainfected macrophages.
Assuntos
Proteínas Ativadoras de GTPase/genética , Macrófagos/metabolismo , Macrófagos/microbiologia , MicroRNAs/genética , Interferência de RNA , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Salmonella typhimurium/fisiologia , Animais , Morte Celular/genética , Regulação da Expressão Gênica , Camundongos , Necrose/genética , Células RAW 264.7 , Infecções por Salmonella/genética , Infecções por Salmonella/metabolismo , Infecções por Salmonella/microbiologiaRESUMO
Excess scarring of the conjunctiva after glaucoma filtration surgery is a major cause of failure. Transforming growth factor (TGF)-ß is critically involved in post-operative scarring. Lithium inhibits TGF-ß-induced gene protein expression in corneal fibroblasts and inhibits TGF-ß-induced epithelial mesenchymal transition. Here, we investigated the effects of LiCl on TGF-ß1-mediated signaling pathways and on myofibroblast transdifferentiation of human Tenon's capsule fibroblasts (HTFs). LiCl treatment reduced expression of TGF-ß1-induced α-SMA expression in HTFs. LiCl also decreased Akt phosphorylation induced by TGF-ß1. TGF-ß1-induced α-SMA expression was significantly decreased by LY294002 and Akt siRNA indicating that these changes are mediated by the PI3K/Akt pathway. Thus, LiCl induces the suppression of transdifferentiation stimulated by TGF-ß1 by the regulation of PI3K/Akt signaling in HTFs.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Fibroblastos/fisiologia , Cloreto de Lítio/metabolismo , Miofibroblastos/fisiologia , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Cicatriz , Fibroblastos/efeitos dos fármacos , Glaucoma/cirurgia , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Cápsula de TenonRESUMO
PURPOSE: This study investigated the effects of the tumor suppressor protein PTEN (phosphatase and tensin homolog) on transforming growth factor (TGF)-ß1-mediated signaling pathways and the transdifferentiation of human subconjunctival fibroblasts (SCFs) after the transduction of this protein containing a transactivator of transcription (Tat) domain. METHODS: The Tat-PTEN expression vector was constructed to express the Tat domain of HIV-1 fused to PTEN. After transduction of the fusion protein and TGF-ß1 stimulation, the dose-dependent effect of the transduced Tat-PTEN fusion protein on Akt phosphorylation and the stability of the Tat-PTEN fusion protein in SCF cells were evaluated by Western blot analysis. The effect of the Tat-PTEN fusion protein on the TGF-ß1-stimulated expression of α-SMA and fibronectin was also evaluated by Western blot analysis and immunocytochemistry. RESULTS: To increase the efficiency of enzyme activity and to successfully deliver this protein to cells, the authors used a PTEN fusion protein that contained the transduction domain of the Tat protein from HIV-1. By Western blot analysis, the transduced Tat-PTEN fusion protein was found to modulate TGF-ß1 signaling in SCF cells and result in the suppression of Akt phosphorylation. Furthermore, the transduction of the Tat-PTEN fusion protein was found to suppress the TGF-ß1-stimulated expression of α-SMA and fibronectin by Western blot analysis and immunocytochemical staining, and the effects of the transduced fusion protein could be controlled in a dose-dependent manner. CONCLUSIONS: The Tat-PTEN fusion proteins were successfully transduced into the SCF cells and induced the suppression of transdifferentiation and fibrosis through the regulation of TGF-ß-mediated signaling. The ability of the Tat-PTEN fusion protein to regulate cell survival could potentially be applied to protein therapy to counteract postoperative scarring in glaucoma surgery.
Assuntos
Túnica Conjuntiva/metabolismo , Regulação da Expressão Gênica/fisiologia , Produtos do Gene tat/genética , PTEN Fosfo-Hidrolase/genética , Fator de Crescimento Transformador beta1/farmacologia , Actinas/metabolismo , Western Blotting , Transdiferenciação Celular/efeitos dos fármacos , Células Cultivadas , Túnica Conjuntiva/citologia , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibronectinas/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Vetores Genéticos , Humanos , Microscopia Confocal , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Recombinantes de Fusão , Transdução de Sinais/efeitos dos fármacos , Transdução GenéticaRESUMO
PURPOSE: To investigate the effects of bortezomib on cell apoptosis and proliferation in human Tenon's capsule fibroblasts (HTFs) after cotreatment with TGF-ß. METHODS: The effect of bortezomib on the apoptosis and cell proliferation of cultured HTFs was determined with FACS analysis and 3-[4,5-demethylthiazol-2,5-diphenyl-2H-tetrazolium bromide] (MTT) assay with or without cotreatment of TGF-ß. The apoptotic effect of cotreatment of bortezomib and TGF-ß through the PI3K/Akt pathway was determined by Western blot analysis. The mRNA level of Bcl-2 and Bax was determined by RT-PCR. p53 expression, DNA-PKcs cleavage, and c-Jun phosphorylation were determined. RESULTS: Cotreatment with bortezomib (5 µM) and TGF-ß (10 µM) increased the proportion of apoptotic cells in HTFs on FACS analysis, whereas either bortezomib or TGF-ß treatment alone did not. The MTT assay also showed that when bortezomib was cotreated with TGF-ß, the cell proliferation of HTFs induced by TGF-ß treatment was significantly decreased at 72-hour incubation. The cotreatment of bortezomib and TGF-ß specifically decreased the Akt phosphorylation induced by TGF-ß, indicating on Western blot analysis that these changes are mediated by the PI3K/Akt pathway. The mRNA level of an apoptosis-related factor, Bcl-2, was significantly reduced, and p53 expression, DNA-PKcs cleavage, and c-Jun phosphorylation were increased after cotreatment. CONCLUSIONS: Bortezomib-induced apoptosis is potentiated by TGF-ß cotreatment in cultured HTFs by inhibition of the PI3K/Akt pathway, indicating that the effect of bortezomib may be potentiated when the level of TGF-ß is elevated, as is observed in the postoperative period.
Assuntos
Apoptose/efeitos dos fármacos , Ácidos Borônicos/farmacologia , Fibroblastos/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazinas/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Western Blotting , Bortezomib , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Fibroblastos/metabolismo , Citometria de Fluxo , Regulação da Expressão Gênica , Genes bcl-2/genética , Humanos , Fosforilação , Inibidores de Proteases/farmacologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/fisiologia , Cápsula de Tenon/patologia , Sais de Tetrazólio , Tiazóis , Fatores de Tempo , Proteína Supressora de Tumor p53/genética , Proteína X Associada a bcl-2/genéticaRESUMO
PURPOSE: To evaluate the influence of H(2)O(2) on lens epithelial cells (LECs) and to determine the effect of the Janus kinase (JAK) inhibitor AG490 and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126 on LEC death after H(2)O(2) exposure. METHODS: Human lens epithelial (HLE) B-3 cells were cultured. Cells were treated for 45 min with H2O2 and signal transducers and activators transcription (STAT) 3, JAK2, and ERK1/2 phosphorylation were surveyed by Western blot analysis. After pretreatment with either 40 microM AG490 or 25 microM U0126, LECs were exposed to H(2)O(2). LEC death was evaluated by microscopy and flow cytometry. RESULTS: H(2)O(2) induced phosphorylation of Tyr-705 STAT3, JAK2, and ERK1/2 in LECs. In cells pretreated with both AG490 and U0126, phosphorylation of Tyr-705 STAT3, JAK2, and ERK1/2 was suppressed. Microscopic findings, however, showed that only AG490 noticeably enhanced cell survival, and flow cytometry showed that cell necrosis decreased to 4.05% after pretreatment with 40 microM AG490. CONCLUSIONS: AG490 may prevent H(2)O(2)-induced LEC death by blocking an unknown necrosis pathway. Further investigation is required to characterize that pathway.
Assuntos
Inibidores Enzimáticos/farmacologia , Células Epiteliais/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Janus Quinases/antagonistas & inibidores , Cristalino/efeitos dos fármacos , Tirfostinas/farmacologia , Anexina A5/metabolismo , Western Blotting , Butadienos/farmacologia , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células Epiteliais/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Citometria de Fluxo , Humanos , Cristalino/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Nitrilas/farmacologia , Estresse Oxidativo , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Transcrição STAT3/metabolismoRESUMO
PURPOSE: To gain a better understanding of the roles of interleukins (ILs) in subconjunctival fibrosis, we investigated their expression in transforming growth factor-beta1 (TGF-beta1)-stimulated Tenon's fibroblasts and examined their association with the transdifferentiation of fibroblasts to myofibroblasts. METHODS: After primary culture, fibroblasts derived from human Tenon's capsule were exposed to TGF-beta1. The expression of alpha-smooth muscle actin (alpha-SMA) protein was assessed by western immunoblots and immunofluorescence. The mRNA levels of various ILs were also evaluated by multiplex reverse transcription (RT)-PCR. Using the small interfering RNAs (siRNAs) specific for IL-6 and IL-11 and the promoter deletion assay, the contributions of IL-6 and IL-11 to TGF-beta1-induced induction of alpha-SMA were determined. RESULTS: In human Tenon's fibroblasts, TGF-beta1 stimulated the expression of alpha-SMA protein determined by western blot analysis and also increased the mRNA levels of IL-6 and IL-11 determined by multiplex RT-PCR. On the western immunoblots and immunofluorescence, the increased expression of alpha-SMA was attenuated only by the siRNAs specific for IL-6 but not by the siRNAs specific for IL-11. When the activator protein-1 binding sites of the IL-6 promoter region were deleted, the stimulation effects of TGF-beta1 decreased. CONCLUSIONS: Our data show that autocrine IL-6 may participate in the TGF-beta1-induced transdifferentiation of human Tenon's fibroblasts to myofibroblasts, which is known to be an essential step for subconjunctival fibrosis.
Assuntos
Transdiferenciação Celular/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Interleucina-6/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Actinas/metabolismo , Western Blotting , Fibroblastos/metabolismo , Imunofluorescência , Humanos , Interleucina-11/genética , Interleucina-11/metabolismo , Interleucina-6/genética , Regiões Promotoras Genéticas/genética , Interferência de RNA/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Deleção de Sequência , Fator de Transcrição AP-1/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Platelet-derived growth factor (PDGF) has a critical role in proliferative vitreoretinopathy (PVR) as a chemoattractant and mitogen for retinal pigment epithelial cells and retinal glial cells. Here, we investigated the potential effects of PDGF on the proliferation of Müller cells and the intracellular signaling pathway mediating these changes. PDGF induced Müller cell proliferation and increased phosphorylation of the PDGF receptor (PDGFR), as shown by an MTT assay and immunoprecipitation analyses. Both effects were blocked by JNJ, a PDGFR-selective tyrosine kinase inhibitor. PDGF also stimulated phosphorylation of c-JNK and Akt. PDGF-induced Müller cell proliferation was significantly reduced by pre-treatment with SP600125 and LY294002, inhibitors of c-JNK and Akt phosphorylation, respectively. Our findings collectively indicate that PDGF-stimulated Müller cell proliferation occurs via activation of the c-JNK and PI3K/Akt signaling pathways. These data provide useful information in establishing the role of Müller cells in the development of proliferative vitreoretinopathy.
Assuntos
Proteínas Quinases JNK Ativadas por Mitógeno/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Fator de Crescimento Derivado de Plaquetas/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Retina/patologia , Vitreorretinopatia Proliferativa/patologia , Animais , Antracenos/farmacologia , Proliferação de Células , Cromonas/farmacologia , Inibidores Enzimáticos/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Morfolinas/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Ratos , Ratos Endogâmicos BN , Receptores do Fator de Crescimento Derivado de Plaquetas/agonistas , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Retina/metabolismo , Vitreorretinopatia Proliferativa/metabolismoRESUMO
PURPOSE: To determine whether insulin-like growth factor (IGF-1) affects transforming growth factor (TGF-beta)- mediated fibronectin accumulation in human lens epithelial cell line (HLE B-3) cells. MATERIALS AND METHODS: HLE B-3 cells were incubated for 24 hours with TGF-beta (10 ng/ mL), IGF-1 (10 ng/mL), or both. Expression of the fibronectin gene was determined using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Fibronectin levels were examined using western blot analysis and immunofluorescence staining. RESULTS: Expression of the fibronectin gene was not different between the TGF-beta/IGF-1 treated group and the TGF-beta treated group (p= 0.116). However, western blot analysis demonstrated decreased fibronectin levels in human lens epithelial cells treated with TGF-beta and IGF-1 compared to those treated with TGF-beta only (p < 0.01). Immunofluorescence staining disclosed inhibition of TGF-beta-induced fibronectin in the presence of IGF-1. CONCLUSION: This study suggests that IGF-1 counteracts TGF-beta-mediated fibronectin accumulation in human lens epithelial cells.
Assuntos
Células Epiteliais/efeitos dos fármacos , Fibronectinas/genética , Fator de Crescimento Insulin-Like I/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Linhagem Celular , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Fibronectinas/metabolismo , Imunofluorescência , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Cristalino/citologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
PURPOSE: Excessive scarring in subconjunctival tissues after filtering surgery seems to be characterized by aberrant extracellular matrix (ECM) production, and tissue transglutaminase (tTgase) plays an important role in this process. In the present study, the effects of transforming growth factor (TGF)-beta2 on the expression of tTgase, its activity in subconjunctival fibroblasts and whether the effects of TGF-beta are mediated by prosurvival signaling pathways were examined. METHODS: Primary subconjunctival fibroblasts treated with TGF-beta2 were examined for the expression of tTgase with Western blot analysis. The modulation of extracellular tTgase activity by TGF-beta2 was measured by both the formation of fibronectin polymers and the ECM protein incorporation of fluorescein cadaverine. The expression of tTgase was analyzed by immunofluorescence staining and Western blot analysis of subconjunctival fibroblasts that were transiently transfected with an Akt dominant negative mutant gene or were treated with an Akt inhibitor or tTgase siRNA. RESULTS: Treatment of subconjunctival fibroblasts with TGF-beta2 caused an increase in activation and expression of tTgase. The effects of TGF-beta stimulation of subconjunctival fibroblasts were twofold, causing both rapid activation of the ERK pathway within minutes of treatment and a more delayed activation of the phosphatidylinositol3-kinase-protein kinase B (PKB)/Akt pathway; however, only Akt activation was necessary for TGF-beta-induced tTgase expression. Transient transfection of subconjunctival fibroblasts with an Akt dominant negative mutant gene, or treatment with an Akt inhibitor (but not with an ERK inhibitor) or tTgase siRNA led to decreased activation and expression of tTgase. CONCLUSIONS: TGF-beta2 activated the PI3K-Akt pathway, and this activation was essential for the expression and activity of tTgase in subconjunctival fibroblasts. The results indicate a novel biological function of the PI3K-Akt pathway in subconjunctival fibroblasts. Elevated expression and activity of tTgase may play an important role in the pathogenesis of diseases related to wound healing and fibrogenic reactions in subconjunctival fibroblasts.
Assuntos
Túnica Conjuntiva/efeitos dos fármacos , Proteínas de Ligação ao GTP/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Crescimento Transformador beta2/farmacologia , Transglutaminases/metabolismo , Western Blotting , Células Cultivadas , Túnica Conjuntiva/citologia , Túnica Conjuntiva/enzimologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/enzimologia , Fibronectinas/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação , Proteína 2 Glutamina gama-Glutamiltransferase , Proteínas Proto-Oncogênicas c-akt/genética , Interferência de RNA , Transfecção , Regulação para CimaRESUMO
TRAIL has been suggested to induce the cell death in various tumor cells but not in normal cells; however, several studies have provided the evidence that TRAIL can induce the cell death in some normal cells including human normal hepatocytes, suggesting that TRAIL may show hepatic toxicity in human. In this study, we designed a pro-form of TRAIL (sTRAIL:IL-18) in that soluble TRAIL (sTRAIL) is fused to IL-18, and a matrix metalloproteinases (MMPs) cleavage site is introduced at the connecting site. We showed that sTRAIL:IL-18 has significantly diminished the killing activity in HeLa cells but regains the activity by releasing the free sTRAIL through MMP-2-mediated cleavage. In addition, the killing activity of sTRAIL:IL-18 was significantly increased in HeLa cells when active MMP-2 was produced by TNF-alpha. Taken together, the data suggested that the sTRAIL:IL-18 can be reactivated at the specialized areas where MMPs are pathologically produced.
Assuntos
Metaloproteinases da Matriz/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Apoptose , Sequência de Bases , DNA Complementar/genética , Células HeLa , Humanos , Interleucina-18/genética , Interleucina-18/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/genética , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
In the course of our screening, N-hydroxy-2-(naphthalene-2-ylsulfanyl)-acetamide (1), which contains a metal-chelating hydroxamate group, has been identified as a potent inhibitor of aminopeptidase N (APN, EC 3.4.11.2). Compound 1 potently inhibited APN activity with a K(i) value of 3.5 microM. It also inhibited the basic fibroblast growth-factor-induced invasion of bovine aortic endothelial cells at low micromolar concentrations.
Assuntos
Acetamidas/farmacologia , Inibidores da Angiogênese/farmacologia , Antígenos CD13/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Ácidos Hidroxâmicos/química , Naftalenos/farmacologia , Animais , Aorta/citologia , Aorta/efeitos dos fármacos , Bovinos , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/antagonistas & inibidoresRESUMO
The aim of this study was to evaluate MR imaging findings of the associated findings in surrounding tissues of the extra-articular soft tissue ganglion cysts around the knee. We retrospectively reviewed MR images of 30 patients who had surgically confirmed extra-articular soft tissue ganglion cysts around the knee with focus on the associated findings in surrounding tissues, such as muscle, subcutaneous fat, bone, and nerve. The most common associated finding was the visualization of channel between ganglion cyst and the joint, which was demonstrated in 20 cases (continuous type in 12 cases and discontinuous type in 8 cases). Other associated findings were seen in 15 cases; pericystic edema ( n=9), bony remodelling ( n=3), and nerve involvement ( n=3). The bony remodelling involved the proximal metaphysis of tibia in all 3 cases. Two patients with nerve involvement had deep peroneal nerve in subacute phase and one involved common peroneal nerve in chronic phase. The MR imaging is a useful imaging modality to evaluate the associated findings in extra-articular soft tissue ganglion cysts around the knee. The evaluation of these associated findings is helpful for the differentiation of ganglion cysts from other cystic lesions around the knee.