RESUMEN
OBJECTIVE: To evaluate the development of speech perception and auditory skills after cochlear implantation in deaf children with asymptomatic congenital cytomegalovirus (CMV) infection diagnosed based on the presence of CMV DNA in the neonatal urine. STUDY DESIGN: A prospective study of congenital CMV infection was done between 1996 and 2003. Of 18 children diagnosed with congenital CMV infection, 2 deaf children with asymptomatic CMV infections received cochlear implantation. RESULTS: The 2 deaf children who received cochlear implantation had delayed-onset, progressive sensorineural hearing loss on follow-up audiometric examinations administered at 29 and 39 months of age. After cochlear implantation, their Infant-Toddler Meaningful Auditory Integration Scale scores increased consistently during 36 months of follow-up; these results were similar to those of 5 congenitally deaf children without CMV infection who had cochlear implantation. CONCLUSIONS: Cochlear implantation was effective for improving the development of speech perception and auditory skills in deaf children with asymptomatic congenital CMV infection. There was no significant difference in the development of useful auditory integration between our general pediatric cochlear implant population without CMV infection and those with asymptomatic CMV infection.
Asunto(s)
Infecciones por Citomegalovirus/congénito , Preescolar , Implantación Coclear/efectos adversos , Infecciones por Citomegalovirus/epidemiología , ADN Viral/orina , Femenino , Estudios de Seguimiento , Audífonos , Pérdida Auditiva Sensorineural/etiología , Humanos , Lactante , Recién Nacido , Japón/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Estudios Prospectivos , Percepción del HablaRESUMEN
For many years, methylparaben (MP) has been used as a preservative in cosmetics. In this study, we investigated the effects of ultraviolet-B (UVB) exposure on MP-treated human skin keratinocytes. HaCaT keratinocyte was cultured in MP-containing medium for 24h, exposed to UVB (15 or 30 mJ/cm(2)) and further cultured for another 24h. Subsequent cellular viability was quantified by MTT-based assay and cell death was qualified by fluorescent microscopy and flow cytometry. Oxidative stress, nitric oxide (NO) production and cellular lipid peroxidation were measured using fluorescent probes. In addition, activation of nuclear factor kappa B and activator protein-1 was assessed by electro-mobility gel-shift assay. Practical concentrations of MP (0.003%) had a little or no effect on cellular viability, oxidative stress, NO production, lipid peroxidation and activation of nuclear transcription factors in HaCaT keratinocytes. Low-dose UVB also had little or no effect on these parameters in HaCaT keratinocytes. However, UVB exposure significantly increased cell death, oxidative stress, NO production, lipid peroxidation and activation of transcription factors in MP-treated HaCaT keratinocytes. These results indicate that MP, which has been considered a safe preservative in cosmetics, may have harmful effects on human skin when exposed to sunlight.
Asunto(s)
Apoptosis , Queratinocitos , Parabenos/toxicidad , Conservadores Farmacéuticos/toxicidad , Piel , Rayos Ultravioleta/efectos adversos , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Células Cultivadas , Espectroscopía de Resonancia por Spin del Electrón , Ensayo de Cambio de Movilidad Electroforética , Citometría de Flujo , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/patología , Queratinocitos/efectos de la radiación , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/efectos de la radiación , Óxido Nítrico/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Piel/efectos de los fármacos , Piel/patología , Piel/efectos de la radiaciónRESUMEN
In this study, we describe the fabrication of novel fullerene-containing peptide-nanoparticles through self-assembly. A water-soluble, poly(l-glutamic acid)-attached fullerene was newly synthesized and the conformation and self-assembling property in water were examined by using circular dichroism, FTIR, UV, atomic force microscopy, and dynamic light scattering measurements. In the lower pH region (<6.8), the fullerene peptide self-assembles into nanoparticles that are ca. 100-200 nm in diameter. These nanoparticles are rich in alpha-helices, and stacking interaction of fullerene moieties contributes to the stability of the high-order structure. In addition, these particle sizes can be easily controlled by changing pH that results in causing the conformational transition of PLGA segment. Finally, the fullerene-containing nanoparticle is confirmed to be capable of removing the biologically important superoxide radical in comparison with the superoxide dismutase.
RESUMEN
The interaction between leukocytes and the vascular endothelial cells (EC) via cellular adhesion molecules plays an important role in various inflammatory and immune diseases. It has been suggested that peroxisome proliferator-activated receptor-gamma (PPAR-gamma, a member of the nuclear receptor superfamily of transcription factors) might be involved in the control of inflammation and in modulating the expression of various cytokines. The aim of this investigation was to evaluate the anti-inflammatory properties of PPAR-gamma activators, as well as the inhibitory effect of PPAR-gamma on the expression of adhesion molecules on leukocytes and vascular endothelial cells. Pioglitazone, a synthetic PPAR-gamma activator, suppressed the increase of CD11b/CD18 expression on FMLP-activated leukocytes, as detected by immunofluorescence flow cytometry. However, the FMLP-induced elevation of cytosolic Ca2+ in leukocytes was not suppressed by pioglitazone. Pioglitazone inhibited the expression of VCAM-1 protein and mRNA on activated human umbilical vein endothelial cells (HUVEC) after IL-1beta stimulation, as detected by ELISA and real-time PCR. However, it showed little effect on the expression of ICAM-1 and E-selectin. The present study revealed that pioglitazone can influence monocyte-EC binding by inhibiting VCAM-1 expression on activated EC and neutrophil-EC binding by inhibiting upregulation of CD11b/CD18 on activated neutrophils. Accordingly, pioglitazone may be useful for treating inflammatory diseases.
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Moléculas de Adhesión Celular/genética , Endotelio Vascular/fisiología , Neutrófilos/fisiología , Tiazolidinedionas/farmacología , Antígenos CD/sangre , Secuencia de Bases , Calcio/sangre , Moléculas de Adhesión Celular/efectos de los fármacos , Células Cultivadas , Cartilla de ADN , Selectina E/genética , Endotelio Vascular/efectos de los fármacos , Citometría de Flujo , Humanos , Hipoglucemiantes/farmacología , Molécula 1 de Adhesión Intercelular/genética , Masculino , Neutrófilos/efectos de los fármacos , Pioglitazona , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Venas Umbilicales , Molécula 1 de Adhesión Celular Vascular/genéticaRESUMEN
A natural compound contained in olive oil, 3,4-dihydroxyphenylethanol (DOPE), is also known as an endogenous metabolite of dopamine. The role of DOPE in oxidative stress-induced cell damage was investigated using differentiated PC12 cells. Superoxide (O(2)(-)) and H(2)O(2) induced a dose-dependent leakage of lactate dehydrogenase (LDH) and decreased cell viability denoted by MTT assay. While O(2)(-) -induced cell damage was not affected by DOPE, pretreatment of the cells with DOPE dose-dependently prevented the leakage of LDH induced by H(2)O(2). In these cells, augmented activity of catalase was demonstrated, while the levels of glutathione and glutathione peroxidase activity remained unchanged. The effect of DOPE was abolished when an inhibitor of catalase 3-amino-l, 2,4-triazole, was included in the medium. DOPE also protected against cell damage induced by H(2)O(2), and Fe(2+). In the hydroxyl radical ((.-)OH) assay using p-nitroso-N, N-dimethylaniline (PNDA), oxidation of PNDA by (.-)OH generated by the Fenton reaction was significantly attenuated in the presence of DOPE. By an electron spin resonance spin trapping study that represents the direct activity of DOPE to scavenge (.-)OH, however, limited scavenging activity was demonstrated for DOPE. Taken together, DOPE may act as a unique cytoprotective compound in nerve tissue subjected to oxidative stress.
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Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Dopamina/metabolismo , Estrés Oxidativo/efectos de los fármacos , Alcohol Feniletílico/análogos & derivados , Alcohol Feniletílico/metabolismo , Amitrol (Herbicida)/farmacología , Animales , Catalasa/metabolismo , Muerte Celular/fisiología , Supervivencia Celular/fisiología , Espectroscopía de Resonancia por Spin del Electrón , Inhibidores Enzimáticos/farmacología , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Peróxido de Hidrógeno/toxicidad , Hierro/toxicidad , L-Lactato Deshidrogenasa/metabolismo , Compuestos Nitrosos/química , Estrés Oxidativo/fisiología , Células PC12 , Ratas , Superóxidos/toxicidadRESUMEN
Singlet oxygen is regarded as contributing to the pathogenesis of various diseases including light-induced skin disorders and inflammatory response. In this study, the correlation between singlet oxygen quenching activity (SOQA) of human serum and blood biochemistry or life-style was evaluated. Healthy volunteers were recruited and carried out a measurement of SOQA by using electron paramagnetic resonance (EPR) and a questionnaire survey about a smoking. It was demonstrated that major quenchers of singlet oxygen in serum are proteins, and small molecular anti-oxidants relatively play a minor role. SOQA of whole sera showed no correlation with protein concentration, but positively correlated with SOQA of small molecular fraction. In vitro studies demonstrated that the decrease of sulfhydryl groups by NO or superoxide significantly attenuated SOQA of albumin. Together, these results may imply that the underlying oxidative condition in each individual influences both small molecular antioxidant states and the sulfhydryl content of serum proteins. SOQA of sera from women with a smoking history was significantly lower compared to non-smoking women, suggesting that the smoking habit impaired the defense mechanism against singlet oxygen.
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Proteínas Sanguíneas/fisiología , Suero , Oxígeno Singlete/sangre , Oxígeno Singlete/fisiología , Adolescente , Adulto , Anciano , Proteínas Sanguíneas/análisis , Espectroscopía de Resonancia por Spin del Electrón , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Estrés Oxidativo , Albúmina Sérica/análisis , Fumar/sangre , Compuestos de Sulfhidrilo/sangre , gammaglobulinas/análisisRESUMEN
A novel vitamin E derivative that is freely soluble in water, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), was evaluated for ability to inhibit development of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits or cholesterol-loaded New Zealand White rabbits. Although TMG rapidly entered the circulation blood after oral administration, the blood TMG concentration remained low, while neither TMG nor its metabolites appeared in the low-density lipoprotein (LDL) fraction. TMG did not decrease serum total cholesterol and the various lipoprotein-associated cholesterol fractions (very LDL-, or high-density lipoprotein- (HDL) cholesterol). TMG reduced the serum concentration of thiobarbituric acid-reactive substances (TBARS; an index of lipid peroxidation) in cholesterol-loaded rabbits but not WHHL rabbits. Nonetheless, TMG inhibited aortic atherosclerosis as effectively as probucol in both models. Our results indicate that TMG opposes progression of atherosclerosis not only by preventing oxidation of LDL, but also by presently unknown mechanisms. Even an antioxidant with no uptake by LDL apparently can inhibit development of atherosclerosis despite a very low serum concentration.