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1.
J Med Virol ; 86(2): 347-53, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24127261

RESUMO

Unlike the case for immunodeficient patients, little is known about polyomavirus (PV) infection in immunocompetent patients. PV infection in immunocompetent individuals has been reported sporadically, but little is known about asymptomatic hematuria. To determine the clinical significance and prevalence of urinary PV infection in immunocompetent patients, a total of 95 individuals admitted to Seoul St. Mary's hospital were investigated. Sixty-four patients were enrolled for evaluation of asymptomatic hematuria, and 31 healthy individuals served as controls. Clinical screening for PV infection was performed by urine cytology analysis by liquid-based preparation and urine RT-PCR for BK virus (BKV) and JC virus (JCV), respectively. The average age of the patients in the PV(+) - and PV(-) -groups with asymptomatic hematuria were 60 years and 46 years, respectively. Urine cytology analysis revealed decoy cells in 37/64 hematuria patients (38.9%), but not in healthy controls. They were more prevalent in male patients. Eighty-two patients (86.3%) had PV viruria, viz., 54/64 patients in the hematuria group and 28/31 in the control group. Interestingly, 28/31 (90.3%) cases in the healthy control group were positive for PV viruria, which exceeded the number in the hematuria group (84.4%). PV viruria was associated primarily with JCV, rather than BKV. PV viruria, including JCV viruria, correlated with urine decoy cells and increased age. In conclusion, urinary PV infection is common in immunocompetent patients with asymptomatic hematuria and is age-related. These data may provide an insight into the pathogenesis and future treatment of asymptomatic hematuria associated with urinary PV infection in immunocompetent patients.


Assuntos
Vírus BK/isolamento & purificação , Hematúria/etiologia , Vírus JC/isolamento & purificação , Infecções por Polyomavirus/complicações , Infecções Urinárias/virologia , Urina/virologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Hematúria/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/epidemiologia , Prevalência , Fatores Sexuais , Infecções Urinárias/epidemiologia , Urina/citologia , Adulto Jovem
2.
J Med Chem ; 55(24): 10863-84, 2012 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-23186287

RESUMO

Deguelin exhibits potent apoptotic and antiangiogenic activities in a variety of transformed cells and cancer cells. Deguelin also exhibits potent tumor suppressive effects in xenograft tumor models for many human cancers. Our initial studies confirmed that deguelin disrupts ATP binding to HSP90 and consequently induces destabilization of its client proteins such as HIF-1α. Interestingly, a fluorescence probe assay revealed that deguelin and its analogues do not compete with ATP binding to the N-terminus of HSP90, unlike most HSP90 inhibitors. To determine the key parts of deguelin that contribute to its potent HSP90 inhibition, as well as its antiproliferative and antiangiogenic activities, we have established a structure-activity relationship (SAR) of deguelin. In the course of these studies, we identified a series of novel and potent HSP90 inhibitors. In particular, analogues 54 and 69, the B- and C-ring-truncated compounds, exhibited excellent antiproliferative activities with IC(50) of 140 and 490 nM in the H1299 cell line, respectively, and antiangiogenic activities in zebrafish embryos in a dose dependent manner (0.25-1.25 µM).


Assuntos
Inibidores da Angiogênese/síntese química , Antineoplásicos/síntese química , Benzopiranos/síntese química , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Rotenona/análogos & derivados , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Benzopiranos/química , Benzopiranos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Embrião não Mamífero/irrigação sanguínea , Embrião não Mamífero/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Ligação Proteica , Rotenona/síntese química , Rotenona/química , Rotenona/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade , Peixe-Zebra
3.
J Water Health ; 8(2): 290-8, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20154392

RESUMO

The degradation of diethyl phthalate (DEP) in an aqueous solution during ozonation was investigated by identifying the oxidation intermediates using GC-MS. The experiments were carried out in semi-batch mode with a 1.5 mg l(-1)-min ozone dose. The proposed degradation pathways were divided into hydrolysis of the aliphatic chain (pathway (A)) and hydroxylation resulting from OH attack in the aromatic ring (pathway (B)). With increasing ozone dose, the aromatic ring of DEP was opened and acidic compounds, such as malonic acid, succinic acid and glutaric acid were formed. In addition, the ozonation of DEP for 18 min induced hydrogen peroxide (H(2)O(2)) generation at levels six times higher than pure water. Of the intermediates indentified, phthalic acid (PA) and phthalic anhydride (PAH) enhanced the degradation of DEP by promoting ozone decomposition.


Assuntos
Ozônio/química , Ácidos Ftálicos/metabolismo , Relação Dose-Resposta a Droga , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Concentração de Íons de Hidrogênio , Oxirredução
4.
Anal Sci ; 21(5): 513-6, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15913138

RESUMO

A rapid and sensitive analytical method using pentafluorothiophenol (PFTP) derivatization was applied to detect diphenylarsinic acid (DPAA) in water. In this study, the optimum derivatization conditions, such as acid concentration, reaction time and reaction temperature, were investigated to develop a suitable procedure for DPAA determination. After extracting the derivatives into benzene, the determination was carried out by gas chromatography/mass spectrometry (GC/MS) with selected ion monitoring (SIM). The detection limit of the method was 9.4 microg/l, and the overall recoveries obtained from real environmental samples were 88.9 - 104.7% and coefficient variations were 5.1 - 13.9%.


Assuntos
Arsenicais/análise , Abastecimento de Água/análise , Água Doce/análise , Cromatografia Gasosa-Espectrometria de Massas , Indicadores e Reagentes , Temperatura
5.
Inflamm Bowel Dis ; 10(5): 564-72, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15472516

RESUMO

Certain irinoid-producing plants have been used as herbal anti-inflammatory remedies. Here we evaluated whether catalposide (CATP), a single compound isolated from irinoid-producing plant Catalpa ovata, has a potential for preventing or ameliorating diseases characterized by mucosal inflammation. Preliminary microarray-based gene expression test revealed that CATP, which alone did not significantly affect expression of any of the >8,000 genes analyzed, attenuated the expression of tumor necrosis factor-alpha (TNF-alpha)-induced proinflammatory genes including interleukin-8 (IL-8) in human intestinal epithelial HT-29 cells. Down-regulation of IL-8 mRNA accumulation was also reflected by the decreased IL-8 secretion in CATP-treated HT-29 cells. The signal transduction study revealed that CATP significantly attenuates TNF-alpha-mediated p38 and extracellular signal-regulated kinase (ERK) phosphorylation. Further, CATP reduced NF-kappaB-mediated transcriptional activation as well as Ikappa-Balpha degradation. To establish the in vivo relevance of these findings, we examined whether CATP could affect intestinal inflammation in vivo using the mouse model of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. Intrarectal administration of CATP dramatically reduced the weight loss, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, CATP suppressed the expression of TNF-alpha, interleukin-1beta, and intercellular adhesion molecule-1 along with the inhibition of NF-kappa B p65 translocation into nucleus in TNBS colitis. Collectively, current results demonstrate that CATP may be an effective agent for the treatment of diseases characterized by mucosal inflammation.


Assuntos
Colite/tratamento farmacológico , Colite/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Inflamação/genética , Animais , Colite/veterinária , Citocinas/análise , Citocinas/biossíntese , Modelos Animais de Doenças , Regulação para Baixo , Inflamação/patologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Índice de Gravidade de Doença , Transdução de Sinais , Trinitrobenzenos/administração & dosagem
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