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1.
PLoS One ; 13(4): e0195083, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29608580

RESUMEN

Ultra-precision face turning of Al6061 mirrors using single point diamond turning (SPDT) was undertaken to investigate the correlation between the surface roughness and reflectance. By reducing the feed rate, the optimal feed rate when the chip formation became unstable was studied. Most importantly, the impact on the roughness and reflectance was examined when the chip formation ceased to be continuous. It was determined that for a feed rate below 3 mm/min, the surface roughness always improved as the feed rate decreased, at the cost of a reduction of the normalized reflectance. The reduction of reflectance was determined to be the result of the lower material removal rates that led to a discontinuous chip formation.


Asunto(s)
Aleaciones/química , Diamante , Modelos Teóricos , Propiedades de Superficie
2.
Clin Radiol ; 69(4): 397-402, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24418670

RESUMEN

AIM: To examine how the location where reading takes place and the availability of prior images can affect performance in breast test-set reading. MATERIALS AND METHODS: Under optimized viewing conditions, 10 expert screen readers each interpreted a reader-specific set of images containing 200 mammographic cases. Readers, randomly divided into two groups read images under one of two pairs of conditions: clinical read with prior images and laboratory read with prior images; laboratory read with prior images and laboratory read without prior images. Region-of-interest (ROI) figure-of-merit (FOM) was analysed using JAFROC software. Breast side-specific sensitivity and specificity were tested using Wilcoxon matched-pairs signed rank tests. Agreement between pairs of readings was measured using Kendall's coefficient of concordance. RESULTS: Group performances between test-set readings demonstrated similar ROI FOMs, sensitivity and specificity median values, and acceptable levels of agreement between pairs of readings were shown (W = 0.75-0.79, p < 0.001) for both pairs of reading conditions. On an individual reader level, two readers demonstrated significant decreases (p < 0.05) in ROI FOMs when prior images were unavailable. Reading location had an inconsistent impact on individual performance. CONCLUSION: Reading location and availability of prior images did not significantly alter group performance.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Competencia Clínica , Mamografía , Garantía de la Calidad de Atención de Salud , Intensificación de Imagen Radiográfica , Competencia Clínica/normas , Toma de Decisiones , Femenino , Humanos , Variaciones Dependientes del Observador , Garantía de la Calidad de Atención de Salud/normas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
3.
Mol Biol (Mosk) ; 47(4): 618-24, 2013.
Artículo en Ruso | MEDLINE | ID: mdl-24466751

RESUMEN

The upregulation of dopaminergic neuronal differentiation is necessary for stem cell therapy in Parkinson's disease (PD). In this study, neuronal differentiation efficiency increased by more than 2 times in P19 embryonic stem cells (ESCs) induced by N-acetylcysteine (NAC) and retinoic acid (RA) as compared to RA alone, with suppressed glial differentiation. The majority of NAC-treated stem cells grafted into brains of PD mice differentiated into dopaminergic neurons and persisted well for 6 weeks. Parkinsonism was also greatly improved after grafting NAC-treated cells in comparison to cells treated with only RA. Our results strongly suggest that NAC treatment may be an effective strategy for generating stem cells fated to become dopaminergic neurons for PD clinical therapy.


Asunto(s)
Acetilcisteína/farmacología , Diferenciación Celular/efectos de los fármacos , Células Madre Embrionarias/efectos de los fármacos , Neuronas/efectos de los fármacos , Trastornos Parkinsonianos/patología , Trastornos Parkinsonianos/terapia , Animales , Encéfalo/patología , Células Cultivadas , Modelos Animales de Enfermedad , Dopamina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Trasplante de Células Madre , Tretinoina/farmacología
4.
Mol Biol (Mosk) ; 46(5): 741-6, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23156673

RESUMEN

We examined whether N-acetylcysteine (NAC) enhanced embryonic body (EB) formation and neuronal differentiation in terms of EB formation, neuronal marker (microtubule-associated protein 2; MAP-2) expression, and neuron maturation using P19 embryonic stem cells. The size and numbers of EBs were greatly increased, together with the up-regulated N-cadherin expression. Also, MAP-2 expression and neurite outgrowth were much increased with activation of serine/threonine protein kinase (Akt) and blocked by addition of an Akt inhibitor (LY294002). Our results suggested that NAC increased EB formation by up-regulating the N-cadherin expression. Furthermore, NAC-enhanced neuronal differentiation was mediated by activation of Akt.


Asunto(s)
Acetilcisteína/farmacología , Cadherinas/metabolismo , Cuerpos Embrioides/metabolismo , Células Madre Embrionarias/efectos de los fármacos , Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Cadherinas/genética , Recuento de Células , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Línea Celular , Cromonas/farmacología , Cuerpos Embrioides/citología , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Ratones , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Morfolinas/farmacología , Neuronas/citología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal/efectos de los fármacos , Activación Transcripcional/efectos de los fármacos
5.
J Med Syst ; 35(4): 657-69, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20703523

RESUMEN

Healthcare services are complex and life-critical. One mistake in any procedure may lead to irremediable consequences; numerous researchers, thus, introduce information and communication technology to improve quality of services and enhance patient safety by reducing the medical errors. Radio frequency identification (RFID) is considered as one of the emerging tool assist in meeting the challenges of the present situation. In recent years, RFID has been applied in medical organizations for the purpose of managing and tracking medical equipment, monitoring and identifying patients, ensuring that the right medication is given to the right patient, and preventing the use of counterfeit medicine. However, most of the existing literature focuses on demonstrating how RFID can benefit the healthcare industry, whereas little attention has been given to the management issues involved in constructing an RFID project in medical organizations. In this paper, an exploratory case study is conducted in a medical organization to illustrate the development framework and critical issues that should be taken into consideration in the preparation, implementation and maintenance stage of constructing such a project. All the experiences and results discussed in this paper offer valuable and useful insights to steer those who would like to start their journey using RFID in medical organizations.


Asunto(s)
Administración de los Servicios de Salud , Dispositivo de Identificación por Radiofrecuencia/organización & administración , Equipos y Suministros , Humanos , Errores Médicos/prevención & control , Registros Médicos , Estudios de Casos Organizacionales , Calidad de la Atención de Salud/organización & administración
6.
J Med Syst ; 35(6): 1605-15, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20703758

RESUMEN

This paper aims to investigate the efficacy and feasibility of Template-based Electronic Medical Record System (TEMRS) and factors for its successful implementation. A TEMRS was designed and implemented in one core clinic of a Hong Kong professional multi-disciplinary medical services provider with four core clinics located in different parts of Hong Kong. Eight doctors participated in the study. Surveys and interviews were conducted to acquire the users' feedback and satisfaction level. The design, development, and the factors related to the success of the implementation of TEMRS were analyzed. In the study period, 3,032 cases were collected. The most encountered diagnosis were upper respiratory tract infection (50.59%), gastroenteritis (10.19%), dermatitis (5.87%), dyspepsia (5.28%) and rhinitis (4.82%). The system gained an overall satisfaction by the users and the most satisfied areas were rapid retrieving the necessary information of patient (75%) and fasten the diagnostic selection (75%). TEMRS is an enabling system which can reduce the user resistance in new technology with its flexibility. The consideration of cost, security, human, technical, data migration and standardization issues are essential in the implementation of the TEMRS and further research should be conducted to expand the TEMRS's implementation in health care system.


Asunto(s)
Comportamiento del Consumidor , Sistemas de Registros Médicos Computarizados/organización & administración , Sistemas de Apoyo a Decisiones Clínicas/organización & administración , Hong Kong , Humanos , Almacenamiento y Recuperación de la Información , Capacitación en Servicio/organización & administración , Entrevistas como Asunto , Encuestas y Cuestionarios , Interfaz Usuario-Computador
7.
Tob Control ; 19(6): 444-50, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20852322

RESUMEN

OBJECTIVE: This study explored the extent to which Malaysian and Thai smokers believe "light" and menthol cigarettes are less harmful than "regular" cigarettes and the correlates of these beliefs. METHODS: The study used data from wave 1 of the International Tobacco Control Southeast Asia Survey. 2006 adult smokers (95.3% male) from Malaysia and 2000 adult smokers (94.5% male) from Thailand were interviewed face to face in 2005. RESULTS: 29% of Malaysian respondents reported currently smoking light cigarettes and 14% menthols, with 19% agreeing that lights are less harmful and 16% agreeing that menthols are less harmful. 38% of Thai respondents reported currently smoking light cigarettes and 19% menthols, with 46% agreeing that lights are less harmful and 35% agreeing that menthols are less harmful. Malaysian smokers reporting current use of light or menthol cigarettes were more likely to believe that they are less harmful. Reported use of lights did not relate to beliefs for Thai respondents. The belief that light and/or menthol cigarettes are less harmful was strongly related to the belief that they have smoother smoke. CONCLUSIONS: The experience of smoother smoke is likely to produce some level of belief in reduced harm, regardless of how brands are labelled and whether or not Federal Trade Commission FTC/International Organisation for Standardisation tar, nicotine and carbon monoxide yield figures are used.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Mentol , Nicotiana , Nicotina/efectos adversos , Fumar/efectos adversos , Adolescente , Adulto , Cultura , Recolección de Datos , Femenino , Humanos , Malasia , Masculino , Persona de Mediana Edad , Breas/efectos adversos , Tailandia , Adulto Joven
8.
IEEE Trans Inf Technol Biomed ; 12(1): 34-41, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18270035

RESUMEN

The Health Insurance Portability and Accountability Act (HIPAA) privacy and security regulations are two crucial provisions in the protection of healthcare privacy. Privacy regulations create a principle to assure that patients have more control over their health information and set limits on the use and disclosure of health information. The security regulations stipulate the provisions implemented to guard data integrity, confidentiality, and availability. Undoubtedly, the cryptographic mechanisms are well defined to provide suitable solutions. In this paper, to comply with the HIPAA regulations, a flexible cryptographic key management solution is proposed to facilitate interoperations among the applied cryptographic mechanisms. In addition, case of consent exceptions intended to facilitate emergency applications and other possible exceptions can also be handled easily.


Asunto(s)
Confidencialidad/legislación & jurisprudencia , Health Insurance Portability and Accountability Act , Medidas de Seguridad , Estudios de Factibilidad , Estados Unidos
9.
Tob Control ; 17(1): 46-52, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18218808

RESUMEN

AIM: To examine the impact of tobacco advertising policy on adult smokers' awareness of tobacco promotion in two developing countries--Malaysia and Thailand. METHODS: Data from 2004 Malaysian and 2000 Thai adult smokers who participated in the baseline wave of the International Tobacco Control Southeast Asia survey (ITC-SEA). Respondents were asked in a face-to-face interview conducted between January and March 2005 to indicate their levels of awareness of tobacco advertising and promotional activities in the last six months. RESULTS: Unprompted awareness of any tobacco marketing activities was very low in Thailand (20%) but significantly higher in Malaysia (53%; OR = 5.6, 95% CI: 3.5 to 8.9, p<0.001). When prompted about specific locations, Thai adult smokers reported very low recall of tobacco advertising where it was banned, being highest around point of sale, particularly street vendors (7.5%). In contrast, Malaysian adult smokers reported significantly higher levels of awareness of tobacco advertising in all locations (range = 17.7% noticing in disco lounges to 59.3% on posters) including where they are notionally banned (for example, billboards). CONCLUSIONS: These findings demonstrate that comprehensive tobacco advertising legislation when well implemented can lead to dramatic decline in awareness of tobacco promotion, thus supporting strong implementation of Article 13 of the Framework Convention on Tobacco Control.


Asunto(s)
Publicidad , Concienciación , Fumar/psicología , Adulto , Actitud Frente a la Salud , Recolección de Datos/métodos , Femenino , Humanos , Malasia , Masculino , Mercadotecnía/métodos , Fumar/efectos adversos , Tailandia , Industria del Tabaco/economía , Industria del Tabaco/legislación & jurisprudencia
10.
J Nanosci Nanotechnol ; 7(8): 2790-4, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17685299

RESUMEN

This paper reports the synthesis of high quality LiYF4, BaYF5, and NaLaF4 nanocrystals by high-temperature co-decomposition of precursors in organic solvents. Their bulk counterparts have long been used as efficient luminescent hosts for various applications including lasers, upconversion fluorescence, and quantum cutters. The particles were characterized using TEM, XRD, dynamic light scattering (DLS), and fluorescence spectrometry. Trifluoroacetic acid (CF3COOH) and the reaction temperature were crucial for the formation of NaLaF4 and LiYF4 nanoparticles. NaLaF4 was not formed without using CF3COOH, only LaF3 and NaF mixture was formed. NaLaF4 nanoparticles were obtained only when CF3COOH was added in the reaction solution and the temperature was > or =330 degrees C. For the synthesis of LiYF4,, in the absence of CF3COOH in the reaction, a mixture of YOF and LiYF4 nanoparticles was formed. Pure LiYF4 particles were obtained only until CF3COOH was added in the reaction at 340 degrees C or above. The nanoparticles were easily dispersed in organic solvents include hexane, toluene, and chloroform and formed transparent colloidal solutions. The ease of doping of these as-synthesized host nanoparticles for designed optical properties was assessed. The LiYF4, BaYF5, and NaLaF4 nanoparticles, co-doped with 20% Ytterbium (Yb) and 2% Erbium (Er), showed bright upconversion fluorescence upon 980 nm NIR excitation, confirming the high quality of as-synthesized nanoparticles. These nanoparticles are potential candidates for nano-optical devices, thin films, telecommunication, and bio-probes.


Asunto(s)
Nanotecnología/métodos , Compuestos de Bario/química , Química Orgánica/métodos , Cristalización , Electroquímica/métodos , Fluoruros/química , Lantano/química , Compuestos de Litio/química , Nanopartículas del Metal/química , Microscopía Electrónica de Transmisión , Modelos Químicos , Nanopartículas/química , Sodio/química , Solventes/química , Temperatura , Difracción de Rayos X
11.
J Microsc ; 225(Pt 2): 170-4, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17359251

RESUMEN

Electron backscattered Kikuchi diffraction methodology was used to identify phases in the interdendrite region of an alloy ZA27. Two Zn-rich hexagonal close-packed structure phases eta and epsilon phases were distinguished using predetermined lattice parameters of the phases. In relation to studies of scanning electron microscopy and X-ray diffraction, electron backscattered diffraction results revealed that the Al-rich precipitates of the alpha phase were from decomposition of the eta'(T), and the four-phase transformation: alpha+epsilon--> T'+eta, had occurred in the epsilon phase after ageing at 150 degrees C for 8 h.

13.
Australas Phys Eng Sci Med ; 26(3): 104-9, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-14626848

RESUMEN

Radiologists use an "Overall impression" rating to assess a suspicious region on a mammogram. The value ranges from 1 to 5. They will definitely send a patient for biopsy if the rating is 4 or 5. They will send the patient for core biopsy when a rating of 3 (indeterminate) is given. We have developed three methods to aid diagnosis of cases with microcalcifications. The first two methods, namely, Bayesian and multiple logistic regression (with a special "cutting score" technique), utilise six parameter ratings which minimise subjectivity in characterising the microcalcifications. The third method uses three parameters (age of patient, uniformity of size of microcalcification and their distribution) in a multiple stepwise regression. For both training set and test set, all three methods are as good as the two radiologists in terms of percentages of correct classification. Therefore, all three proposed methods potentially can be used as second readers.


Asunto(s)
Algoritmos , Enfermedades de la Mama/clasificación , Enfermedades de la Mama/diagnóstico por imagen , Calcinosis/clasificación , Calcinosis/diagnóstico por imagen , Mamografía/métodos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Enfermedades de la Mama/patología , Calcinosis/patología , Diagnóstico por Computador/métodos , Diagnóstico Diferencial , Humanos , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad
14.
Water Sci Technol ; 47(9): 65-70, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12830942

RESUMEN

The effects of estradiol-17beta, methyltestosterone, tributyltin, bisphenol A and 2,4-dinitrophenol on sex differentiation were investigated in the Korean rockfish, Sebastes schlegeli. The 51 day-old fry with undifferentiated gonads were fed with food containing the chemicals at 0.05, 0.5, 5, 50 and 100 micro/g diet for 29 days. Sex ratio and gonadal abnormality after the chemical treatment were determined by histological examination of gonads. In control group, the sex ratio of fry was 1:1.3 (female:male), and more males than females appeared. The sex of fry fed with estradiol-17beta at 5, 50 and 100 micro/g diet was all females. Feminization of the fry was induced by exogenic estradiol-17beta. In the methyltestosterone group, sex ratio of fry was 1:10.2 in 0.05 micro/g diet, 1:2.4 in 0.5 micro/g diet, 1:3.1 in 5 micro/g diet, 1:1.2 in 50 micro/g diet and 1:2.3 in 100 micro/g diet. Masculinization of the fry was induced by methyltestosterone at the lowest concentration. Furthermore, intersex of the fry was observed. The number of intersex fry was 23.3, 25.0 and 35.3 at 0.5, 5 and 50 micro/g diet of methyltestosterone, respectively. Sex ratio of bisphenol A group showed no difference with that of the control. The sex of fry fed with 2,4-dinitrophenol at 5, 50 and 100 micro/g diet was all females. 2,4-dinitrophenol should be considered as a new member of endocrine disruptors. In tributyltin group, the sex ratio of fry at 100 micro/g diet of tributyltin was 5.4:1. Tributyltin induced the feminization of the fry at the highest dose. Tributyltin showed an estrogenic effect in the Korean rockfish in contrast to an androgenic effect in gastropods.


Asunto(s)
Sistema Endocrino/efectos de los fármacos , Peces/crecimiento & desarrollo , Diferenciación Sexual/efectos de los fármacos , Contaminantes Químicos del Agua/envenenamiento , Administración Oral , Animales , Dieta , Femenino , Masculino
15.
Water Sci Technol ; 47(3): 249-53, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12639037

RESUMEN

Coliform bacteria isolated from the aquatic environment were investigated for antibiotic susceptibility and detailed structures of class 1 integrons. A high proportion of isolates were found to be resistant to sulfamethoxazole, aminoglycosides, and beta-lactams. The 750 (53.6%) isolates were resistant to one or more of the antibiotics tested out of 1,400 coliform bacteria. Based on the MIC of antibiotics and antibiogram, 150 isolates were selected and further studied for class 1 integrons. The intI1 gene was found in 36 (24.0%) of the 150 isolates. Twelve isolates carried the gene cassettes responsible for antibiotic resistance, while no gene cassettes were found in 24 isolates. Seven different genes, dfrA5, dfrA7, dfrA12, dfrA17, aaA2, aaA5, and aad(3'), were detected in gene cassettes. The dfrA and aad genes located on class 1 integrons were responsible for resistance to trimethoprim and aminoglycosides. The remaining 24 coliform bacteria had the incomplete or non-functional class 1 integrons. These results indicated that antibiotic selective pressures may play an important role to maintain gene cassettes of class 1 integrons and in the absence of sustained antibiotic pressures, such as the aquatic environment, coliform bacteria may carry empty or non-functional class 1 integrons.


Asunto(s)
Farmacorresistencia Microbiana , Enterobacteriaceae/genética , Enterobacteriaceae/patogenicidad , Integrones/genética , Selección Genética , Genética de Población , Dinámica Poblacional
16.
Environ Technol ; 23(4): 437-44, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12088371

RESUMEN

The objective of this study was to investigate the biodegradation of gaseous benzene in a biofilter inoculated with benzene-oxidizing microorganisms. The biofilter performance was monitored in terms of benzene removal efficiency and carbon dioxide production. The biofilter was capable of achieving as much as 96% benzene removal efficiency at a residence time of 2 min and an inlet concentration of 220 ppm. During operation with an inlet benzene of 220 ppm, the maximum elimination capacity of the biofilter was 483 g of C6H6 m(-3) day(-1). Under the same conditions, carbon dioxide with a concentration of up to 726 ppm was produced. It was found that carbon dioxide wasproduced at a rate of 608 mg day(-1), which corresponded to a volume of 0.35 l day(-1). Observable features of the microorganisms, meaning microbial activity occurrence in the biofilter, were investigated with the microscopy analysis.


Asunto(s)
Benceno/metabolismo , Bacterias , Biodegradación Ambiental , Filtración , Gases , Membranas Artificiales
17.
J Pharmacol Exp Ther ; 299(3): 874-82, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11714871

RESUMEN

trans-Resveratrol (3,5,4'-trihydroxy-trans-stilbene) has been reported to confer chemoprotection against 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenicity in a murine model. A potential mechanism for this effect by trans-resveratrol is inhibition of DMBA-bioactivating cytochrome P450 (CYP) enzymes such as CYP1B1, CYP1A1, and CYP1A2. In the present study, we examined in detail the in vitro inhibitory effects of trans-resveratrol on these three human CYP enzymes. trans-Resveratrol decreased 7-ethoxyresorufin O-dealkylation activity catalyzed by human recombinant CYP1B1, CYP1A1, and CYP1A2 in a concentration-dependent manner and by a mixed type of inhibition. This direct inhibition was enzyme-selective, as judged by the differences in the apparent K(i) values (0.8 +/- 0.1 microM, 1.2 +/- 0.1 microM, and 15.5 +/- 1.1 microM for CYP1B1, CYP1A1, and CYP1A2, respectively). Preincubating recombinant CYP1A2 or human liver microsomes with trans-resveratrol and NADPH prior to the initiation of substrate oxidation resulted in a time- and concentration-dependent decrease in catalytic activity. The inactivation of liver microsomal CYP1A2 by trans-resveratrol required NADPH, was not reversible by dialysis, and was not affected by the trapping agents glutathione, N-acetylcysteine, catalase, or superoxide dismutase, but was attenuated by a CYP1A2 substrate, imipramine. Analysis of a panel of individual human liver microsomes showed intersample differences in the response to the in vitro inactivation by trans-resveratrol. In contrast to CYP1A2, CYP1B1 was not subject to inactivation by this compound and the reduction in CYP1A1 activity was time- but not concentration-dependent. In summary, trans-resveratrol differentially inhibited human CYP1 enzymes and this occurred by two distinct mechanisms: direct inhibition (mainly CYP1B1 and CYP1A1) and mechanism-based inactivation (CYP1A2).


Asunto(s)
Hidrocarburo de Aril Hidroxilasas , Inhibidores del Citocromo P-450 CYP1A2 , Inhibidores Enzimáticos/farmacología , Estilbenos/farmacología , Unión Competitiva , Citocromo P-450 CYP1A1/antagonistas & inhibidores , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP1B1 , Inhibidores Enzimáticos del Citocromo P-450 , Sistema Enzimático del Citocromo P-450/metabolismo , Humanos , Técnicas In Vitro , Cinética , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Microsomas Hepáticos/metabolismo , NADP/metabolismo , Oxazinas/metabolismo , Proteínas Recombinantes/antagonistas & inhibidores , Resveratrol , Especificidad por Sustrato
18.
J Neurosci Res ; 65(5): 403-7, 2001 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-11536323

RESUMEN

In the present study, we investigated effects of estrogen on cell death induced by carboxy-terminal fragment of amyloid precursor protein (CT), a candidate causative substance in the pathogenesis of Alzheimer's disease. 17 beta-Estradiol attenuated CT-induced cell death in PC12 cells, whereas 17 alpha-estradiol, nonestrogenic stereoisomer, did not exert any significant protective effect on CT-induced cell death. These results suggest that protective effects of estrogen may be mediated by estrogen receptor (ER) in PC12 cells. To confirm the results, we determined the effects of tamoxifen, an estrogen receptor antagonist. Tamoxifen blocked the protective effects of 17 beta-estradiol, although it did not affect those of 17 alpha-estradiol. Overall, it might be thought that the protective effect of estradiol on CT-induced cell death is achieved by hormonal properties mediated through the estrogen receptor rather than the structural properties as a reducing agent.


Asunto(s)
Precursor de Proteína beta-Amiloide/metabolismo , Dióxido de Carbono/toxicidad , Muerte Celular/efectos de los fármacos , Estradiol/farmacología , Fármacos Neuroprotectores/farmacología , Fragmentos de Péptidos/toxicidad , Receptores de Estrógenos/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Animales , Dióxido de Carbono/antagonistas & inhibidores , Muerte Celular/fisiología , Antagonistas de Estrógenos/farmacología , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Células PC12/efectos de los fármacos , Células PC12/metabolismo , Células PC12/patología , Fragmentos de Péptidos/antagonistas & inhibidores , Estructura Terciaria de Proteína/efectos de los fármacos , Estructura Terciaria de Proteína/fisiología , Ratas , Receptores de Estrógenos/efectos de los fármacos , Tamoxifeno/farmacología
19.
J Neurochem ; 78(1): 109-20, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11432978

RESUMEN

One of the pathophysiological features of Alzheimer's disease is astrocytosis around senile plaques. Reactive astrocytes may produce proinflammatory mediators, nitric oxide, and subsequent reactive oxygen intermediates such as peroxynitrites. In the present study, we investigated the possible role of the C-terminal fragment of amyloid precursor protein (CT-APP), which is another constituent of amyloid senile plaque and an abnormal product of APP metabolism, as an inducer of astrocytosis. We report that 100 nM recombinant C-terminal 105 amino acid fragment (CT105) of APP induced astrocytosis morphologically and immunologically. CT105 exposure resulted in activation of mitogen-activated protein kinase (MAPK) pathways as well as transcription factor NF-kappaB. Pretreatment with PD098059 and/or SB203580 decreased nitric oxide (NO) production and nuclear factor-kappa B (NF-kappaB) activation. But inhibitors of NF-kappaB activation did not affect MAPKs activation whereas they abolished NO production and attenuated astrocytosis. Furthermore, conditioned media derived from CT105-treated astrocytes enhanced neurotoxicity and pretreatment with NO and peroxynitrite scavengers attenuated its toxicity. These suggest that CT-APP may participate in Alzheimer's pathogenesis through MAPKs- and NF-kappaB-dependent astrocytosis and iNOS induction.


Asunto(s)
Precursor de Proteína beta-Amiloide , Gliosis/inducido químicamente , Neurotoxinas , Fragmentos de Péptidos , Precursor de Proteína beta-Amiloide/farmacología , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Células Cultivadas , Inducción Enzimática , Humanos , Proteínas Quinasas Activadas por Mitógenos/fisiología , FN-kappa B/fisiología , Neurotoxinas/farmacología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo II , Fragmentos de Péptidos/farmacología , Ratas
20.
Biochem Biophys Res Commun ; 284(2): 261-7, 2001 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-11394871

RESUMEN

3-hydroxykynurenine (3HK), an endogenous metabolite of tryptophan in the kynurenine pathway, is a potential neurotoxin in several neurodegenerative disorders. Stabilizing protein structure, heat shock proteins (HSPs) have diverse roles as molecular chaperones to mediate stress tolerance. In the present study, we investigated the possible protective role of HSPs against 3HK induced neuronal cell death. Here we report that 3HK induced in a dose- and time-dependent manner neuronal cell death in neuroblastoma SK-N-SH cells. The cell death showed characteristic apoptotic features such as cell shrinkage, plasma membrane blebbing, chromatin condensation, and nuclear condensation and fragmentation. Furthermore, SK-N-SN cells were protected from 3HK induced cytotoxicity by prior elevation of HSPs expression. Our results show that the protective effect was abolished by HSP90 anti-sense oligonucleotides while not by HSP27 and HSP70 anti-sense oligonucleotides. Also, our result shows that HSP90 effectively inhibits caspases activities leading to the apoptosis. These results suggest that 3HK induces apoptosis in neuroblastoma SK-N-SN cells and that HSP90 is major contributing protein component of protection against 3HK induced apoptosis.


Asunto(s)
Apoptosis , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas de Choque Térmico , Quinurenina/análogos & derivados , Quinurenina/toxicidad , Neuroblastoma/metabolismo , Neuronas/metabolismo , Apoptosis/efectos de los fármacos , Bisbenzimidazol , Western Blotting , Caspasas/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citoprotección/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Proteínas de Choque Térmico HSP27 , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/genética , Proteínas HSP90 de Choque Térmico/farmacología , Respuesta al Choque Térmico , Humanos , Quinurenina/antagonistas & inhibidores , Chaperonas Moleculares , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neuroblastoma/patología , Neuronas/citología , Neuronas/efectos de los fármacos , Oligonucleótidos Antisentido/farmacología , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/metabolismo , Temperatura
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