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BACKGROUND: Rehabilitation is widely advocated and provided as a standard of care for patients with total knee arthroplasty (TKA) but its effects on intermediate- to longer-term physical function is unclear. Also unknown is the relationship between the number of rehabilitation sessions attended and functional outcomes. METHODS: We conducted a prospective cohort study of 1540 patients who had undergone TKA and were referred for rehabilitation. Physical function was indexed by the Short-Form 36 (SF-36) physical function score at 6 months post-TKA. We used multivariable linear regression to assess the association between rehabilitation attendance and Month-6 physical function. Among patients who attended rehabilitation, multivariable linear regression was used to examine the dose-response association between the number of sessions attended and Month-6 physical function. RESULTS: Of the 1540 patients, 68 patients did not attend rehabilitation, 86 patients attended one session, and 1386 patients attended two or more sessions. Adjusted for the propensity to attend rehabilitation, rehabilitation attendance was independently associated with better Month-6 SF-36 physical function (point estimate, 5.0 points; 95% CI, 0.5-9.5; P = 0.028 compared with patients with no rehabilitation). Among patients who attended rehabilitation, attending five sessions was associated with a 3.6-point increase in SF-36 scores (95% CI, 0.8-6.5; P = 0.01) relative to patients who attended one session. CONCLUSIONS: Rehabilitation attendance post-TKA is associated with an increase in self-report physical function. Among patients who attended rehabilitation, a modest dose-response relationship was observed between the number of sessions and functional outcomes.
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Actividades Cotidianas , Artroplastia de Reemplazo de Rodilla/rehabilitación , Articulación de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/cirugía , Anciano , Estudios de Cohortes , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Singapur , Resultado del TratamientoRESUMEN
Endovascular aortic aneurysm repair (EVAR) is now an established technique for treating many patients with infrarenal abdominal aortic aneurysm. Familiarity with the complications associated with this technique and understanding treatment options are crucial for the lifelong performance of stent graft. This pictorial review article describes the currant role of different imaging modalities in surveillance and discusses the complications and its management strategies.
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Aneurisma de la Aorta Abdominal/diagnóstico , Aneurisma de la Aorta Abdominal/cirugía , Disección Aórtica/diagnóstico , Disección Aórtica/cirugía , Prótesis Vascular/efectos adversos , Radiografía Intervencional/métodos , Stents/efectos adversos , HumanosRESUMEN
An outbreak of acute hemorrhagic conjunctivitis (AHC) was reported in Singapore military camps in the year 2005. A total of 103 conjunctival swab specimens were collected from military personnel diagnosed clinically with AHC. PCR testing on these conjunctival specimens revealed the presence of an enterovirus, and this was confirmed by virus isolation. Molecular typing using a partial VP1 gene confirmed a variant of coxsackievirus A24 (CA24v) as the most likely etiological agent for the outbreak. Full-length genome sequencing was carried out on 2 selected virus strains, DSO-26SIN05 and DSO-52SIN05. Sequence comparison and phylogenetic analyses of the VP4, VP1 and 3Cpro gene regions were performed, clustering the Singapore CA24v strains with viruses originating from Asia in the post-2000 era. In addition, we report evolution rates of 4.2 x 10(-3) and 1.0 x 10(-3) nucleotide/year, respectively, for the VP4 capsid and 3Cpro gene regions. Our result shows a focal evolutionary point around 1965-1966, suggesting that the CA24v virus has been evolving constantly since its emergence in Singapore, nearly 40 years ago.
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Conjuntivitis Hemorrágica Aguda/epidemiología , Infecciones por Coxsackievirus/epidemiología , Brotes de Enfermedades , Enterovirus Humano C/clasificación , Enterovirus Humano C/aislamiento & purificación , Personal Militar , Proteasas Virales 3C , Proteínas de la Cápside/genética , Conjuntiva/virología , Conjuntivitis Hemorrágica Aguda/virología , Infecciones por Coxsackievirus/virología , Cisteína Endopeptidasas/genética , Enterovirus Humano C/genética , Evolución Molecular , Humanos , Datos de Secuencia Molecular , Filogenia , Análisis de Secuencia de ADN , Singapur/epidemiología , Proteínas Virales/genéticaRESUMEN
It is known that there is abnormal osteopontin (OPN) expression at the sites of atherosclerotic lesions. In the Apolipoprotein E gene knockout (ApoE-KO) mouse, a model of the atherosclerotic process, altered cholesterol metabolism with associated increase in OPN expression is evident at 12-22 weeks in the aorta and at 22 weeks in the heart. In this study, we analyzed another animal model of hypothyroid mice created by ingestion of propylthiouracil (PTU). After 2 weeks of PTU ingestion, the animals had significant decreases in thyroid hormones (T3 and T4) and immediate increases in blood lipids/cholesterol. Hypothyroid mice showed 1.3-, 1.5-, 2-fold increases in blood levels of total cholesterol, triglycerides, and low density lipoprotein-cholesterol respectively. Semi-quantitative RT-PCR analysis showed that hypothyroid mice had 1.4- to 2-fold increases of OPN mRNA expression in the aorta and 1.5-fold increases in the heart. Hypothyroid animals treated with T3 (5 microg/day for 6 days) or statin (0.2 mg/30 g for 2 weeks) reduce blood lipids and aortic OPN mRNA expression. Data obtained with ELISA analyses showed 1.5- and 1.7-fold increases in OPN protein in the aorta (10 weeks) and the heart (22 weeks), respectively. This increase is close to the mRNA expression in both tissues of hypothyroid mice. In addition, western blots showed several variants of OPN protein expressed in the aorta and the heart. The decrease in the 70 kDa OPN is accompanied by an increase in 45 kDa OPN in the aorta of hypothyroid mice. In contrast, only 45 kDa OPN is found in the heart of control and hypothyroid mice. These data indicate that the increase of OPN mRNA and protein expression occurs in cardiovascular tissues of hypothyroid mice.
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Aorta/metabolismo , Regulación de la Expresión Génica , Corazón/fisiología , Hipotiroidismo/genética , Propiltiouracilo/farmacología , Sialoglicoproteínas/biosíntesis , Animales , Apolipoproteínas E/genética , Aterosclerosis/patología , Presión Sanguínea , Western Blotting , Peso Corporal , Sistema Cardiovascular , Colesterol/metabolismo , LDL-Colesterol/metabolismo , Modelos Animales de Enfermedad , Electroforesis en Gel de Agar , Ensayo de Inmunoadsorción Enzimática , Frecuencia Cardíaca , Hipotiroidismo/patología , Lípidos/química , Masculino , Ratones , Ratones Endogámicos ICR , Ratones Noqueados , Ratones Transgénicos , Modelos Estadísticos , Miocardio/metabolismo , Osteopontina , ARN/metabolismo , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sialoglicoproteínas/metabolismo , Tiroxina/metabolismo , Factores de Tiempo , Triglicéridos/metabolismo , Triyodotironina/metabolismoRESUMEN
INTRODUCTION: To highlight recent advances in the management of osteoporotic compression fractures of the spine. METHODS: A MEDLINE search was conducted from January 1975 to October 2001. Keywords included osteoporotic compression fractures, osteoporosis and spine fractures. RESULTS: Osteoporotic fractures of the spine often cause significant morbidity to the elderly individual. Diagnosis requires a detailed history and physical examination and investigations are usually required to exclude other causes of back pain. Magnetic resonance imaging (MRI) is often helpful in excluding other causes of pathologic fracture but may not be confirmatory. Conservative treatment was the traditional approach, but newer percutaneous treatments, such as vertebroplasty and kyphoplasty, are safe and simple day surgery procedures which allow for rapid recovery of symptoms and prevention of increasing spinal deformity. Neurological deficit as a result of spinal canal compromise from retropulsed fragments, though relatively uncommon, is well recognised as a cause of significant morbidity and is a major indication for open spinal surgery. Various spinal approaches including anterior or posterior decompression combined with a variety of stabilisation techniques have been reported in the literature. Rehabilitation is often required to improve physical function. CONCLUSIONS: Osteoporotic fractures of the spine are a common cause of morbidity in the elderly. Patients who have persistent pain despite conservative treatment require investigation to exclude other pathological causes of fracture. Percutaneous vertebroplasty and kyphoplasty are new techniques that offer much promise in the treatment of these elderly patients. Open surgery may still be required where there is significant neurologic compromise.
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Procedimientos Ortopédicos , Osteoporosis/complicaciones , Fracturas de la Columna Vertebral/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Indicadores de Salud , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Fracturas de la Columna Vertebral/diagnóstico , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiologíaRESUMEN
The primary objective of this study was to investigate the feasibility of using PEO-PPO-PEO non-ionic copolymeric micelles as a carrier for eye-drop gene delivery of plasmid DNA with lacZ gene in vivo. Using pyrene fluorescence probe methods, zeta potential, and dynamic light scattering test (DLS), the ability of micelle formation of these block copolymers with plasmid was studied. Gene expressions were visualized by both the quality of enzymatic color reaction using X-gal staining and by the quantification of the substrate chlorophenol red galactopyranoside (CPRG) in enucleated eyes on day 2 after gene transfer. In addition, microscopy to identify the types of cell showing uptake and expression of the transferred gene was used. We found that the block polymeric micelles were formed above 0.1% (w/v) of block copolymer with a size of 160 nm and a zeta potential of -4.4 mV. After 2 days of topically delivery three times a day, the most intense gene expression was observed on days 2 and 3. Reporter expression was detected around the iris, sclera, conjunctiva, and lateral rectus muscle of rabbit eyes and also in the intraocular tissues of nude mice upon in vivo topical application for 48 h with a DNA/polymeric micelle formulation. Furthermore, after two enhancement treatments, the transport mechanisms of the block copolymeric micelles were found through endocytosis in tissues by enhancement through the tight junction pathway. Thus, efficient and stable transfer of the functional gene could be achieved with PEO-PPO-PEO polymeric micelles through topical delivery in mice and rabbits. These in vivo experiments indicate the possible potential use of block copolymers for DNA transfer.
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Ojo/metabolismo , Técnicas de Transferencia de Gen , Micelas , Soluciones Oftálmicas , Polietilenglicoles , Glicoles de Propileno , Animales , Citocalasina B/farmacología , Ácido Edético/farmacología , Estudios de Factibilidad , Colorantes Fluorescentes , Luz , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Plásmidos , Conejos , Dispersión de Radiación , TransfecciónRESUMEN
The primary objective of this study was to investigate the effect of geniposide, a potent anti-inflammatory, on ovalbumin-antigen-induced tracheal permeability and transepithelial electrical resistance in guinea pigs. Two weeks after sensitization with ovalbumin (100 mg/ml), the permeability of guinea-pig tracheas was evaluated by flux measurements using the transcellular tracer, [(14)C]estradiol, and the paracellular tracer, [(14)C]mannitol. The effect of extracellular Ca(2+) with geniposide was also studied, using deletion of Ca(2+) in the donor chamber. The in vivo treatment effect of aerosolized geniposide on tracheal permeability in the ovalbumin-sensitized guinea pigs was also evaluated. The results indicate that tight junction permeability of ovalbumin-sensitized trachea was significantly dose dependent and decreased by geniposide (1-10 mM), as evidenced by substantial recovery of transepithelial electrical resistance and decreased transepithelial permeability of [(14)C]mannitol at (1.32+/-0.12) x 10(-5) cm/s. The effect of combination of the removal of extracellular Ca(2+) with geniposide had no effect on tight junction permeability of ovalbumin-sensitized trachea and revealed that transepithelial electrical resistance and junction permeability did not recover. In addition, the cAMP levels and phosphodiesterase activity were not significantly influenced in ovalbumin-sensitized tracheal tissues after geniposide treatment. Inhaled geniposide (50 mM, 30 min after ovalbumin sensitization) significantly restored junction permeability induced by ovalbumin (100 mg/ml, 2 min). Junction permeability did not recover on pretreatment with geniposide (50 mM for 30 min over 16 days consecutive before ovalbumin sensitization) after exposure of conscious guinea pigs to aerosol ovalbumin. In conclusion, geniposide has inhibitory effects on ovalbumin-induced junction permeability and recovery of transepithelial electrical resistance in guinea pig trachea, showing its potential as anti-asthma therapy.
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Antiinflamatorios/provisión & distribución , Iridoides , Piranos/administración & dosificación , Tráquea/efectos de los fármacos , Aerosoles , Animales , Calcio/metabolismo , AMP Cíclico/metabolismo , Cobayas , Masculino , Manitol/farmacocinética , Ovalbúmina/inmunología , Permeabilidad , Uniones Estrechas/efectos de los fármacos , Tráquea/metabolismoRESUMEN
The primary objective of this study was to investigate the feasibility of PEO-PPO-PEO copolymer gel as a release vehicle for percutaneous administration of fentanyl in vitro and in vivo. A cellulose membrane and nude mouse skin with series concentrations of PEO-PPO-PEO block copolymers were used to examine the sustained-release pattern and permeation of fentanyl. The in vivo percutaneous absorption was examined using rabbits to evaluate the preliminary pharmacokinetics of fentanyl with 46% PEO-PPO-PEO copolymer formulation patches. The micelle formation ability of this block copolymer and the penetration ability of PEO-PPO-PEO copolymer over time were also studied by pyrene fluorescence probe methods and the dynamic light scattering test. At a concentration of 46% at 37 degrees C, PEO-PPO-PEO copolymers formed a gel and showed a pseudo-zero-order sustained-release profile. With increasing concentration of copolymer in the cellulose membrane transport, the apparent release flux of fentanyl (200 microgram/ml) decreased to 1. 09+/-0.19 microgram cm(-2) h(-1). Assessment of the effect of the copolymer on nude mouse skin also showed a decrease in the apparent permeability coefficient [(P(H(2)O))=2.24+/-0.47x10(-6) cm s(-1) vs. (P(46% block copolymer))=0.93+/-0.23x10(-7) cm s(-1)]. The preliminary pharmacokinetics of the fentanyl patch was shown to be in steady state within 24 h, and this was maintained for at least 72 h with an elimination half-life (t(1/2)) of 10.5+/-3.4 h. A fluorescence experiment showed polymeric micelle formation of PEO-PPO-PEO copolymers at 0.1% (w/w) within 50 nm micelle size and the PEO-PPO-PEO copolymers were able to penetrate nude mouse skin within 24 h. Thus, it appears that fentanyl preparations based on PEO-PPO-PEO copolymer gel might be practical for percutaneous delivery.
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Analgésicos Opioides/administración & dosificación , Fentanilo/administración & dosificación , Polietilenglicoles/administración & dosificación , Polímeros/administración & dosificación , Glicoles de Propileno/administración & dosificación , Absorción Cutánea , Administración Cutánea , Animales , Estradiol/administración & dosificación , Estradiol/farmacocinética , Fentanilo/farmacocinética , Geles , Masculino , Manitol/administración & dosificación , Manitol/farmacocinética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Micelas , Vehículos Farmacéuticos , ConejosRESUMEN
OBJECTIVES: To prospectively evaluate scrotal ultrasonography (SUS) in patients presenting with scrotal symptoms and to make recommendations about use of SUS in clinical practice. PATIENTS AND METHODS: Forty-eight men with scrotal symptoms were examined by a urologist and independently underwent SUS by one radiologist with no knowledge of the clinical diagnosis. The clinical and SUS diagnoses were compared and the effect on subsequent management recorded. RESULTS: The clinical and SUS diagnoses agreed in 35 men (73%) although SUS provided an additional diagnosis in half of these men. The SUS diagnosis differed in 13 men (27%) although the management was altered in only four patients. CONCLUSION: The clinical diagnosis is correct in most men with scrotal symptoms; the routine use of SUS is inappropriate and should be reserved for specific indications.
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Enfermedades de los Genitales Masculinos/diagnóstico por imagen , Escroto/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , UltrasonografíaRESUMEN
Nidogen-1 (entactin) acts as a bridge between the extracellular matrix molecules laminin-1 and type IV collagen, and thus participates in the assembly of basement membranes. To investigate the role of nidogen-1 in regulating cell-type-specific gene expression in mammary epithelium, we designed a culture microecosystem in which each component, including epithelial cells, mesenchymal cells, lactogenic hormones and extracellular matrix, could be controlled. We found that primary and established mesenchymal and myoepithelial cells synthesized and secreted nidogen-1, whereas expression was absent in primary and established epithelial cells. In an epithelial cell line containing mesenchymal cells, nidogen-1 was produced by the mesenchymal cells but deposited between the epithelial cells. In this mixed culture, mammary epithelial cells express (beta)-casein in the presence of lactogenic hormones. Addition of either laminin-1 plus nidogen-1, or laminin-1 alone, to mammary epithelial cells induced (beta)-casein production. We asked whether recombinant nidogen-1 alone could signal directly for (beta)-casein. Nidogen-1 did not induce (beta)-casein synthesis in epithelial cells, but it augmented the inductive capacity of laminin-1. These data suggest that nidogen-1 can cooperate with laminin-1 to regulate (beta)-casein expression. Addition of full-length nidogen-1 to the mixed cultures had no effect on (beta)-casein gene expression; however, a nidogen-1 fragment containing the laminin-1 binding domain, but lacking the type IV collagen-binding domain, had a dominant negative effect on (beta)-casein expression. These data point to a physiological role for nidogen-1 in the basement membrane-induced gene expression by epithelial cells.
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Regulación de la Expresión Génica , Laminina/fisiología , Glándulas Mamarias Animales/fisiología , Glicoproteínas de Membrana/fisiología , Animales , Caseínas/antagonistas & inhibidores , Caseínas/biosíntesis , Células Cultivadas , Técnicas de Cocultivo , Células Epiteliales/metabolismo , Células Epiteliales/fisiología , Femenino , Laminina/metabolismo , Glándulas Mamarias Animales/citología , Glándulas Mamarias Animales/metabolismo , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Mesodermo/metabolismo , Ratones , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/fisiología , Unión Proteica , Proteínas Recombinantes/farmacología , Transducción de Señal/fisiologíaRESUMEN
A critical challenge for care providers is improving the outcomes for premature infants. The issues of how to control various kinds of stimulation, provide appropriate sensory stimulation, and maintain the quality of life of premature infants becomes the central focus of care given in neonatal intensive care units. Therefore, intervention research studies that improve the development and quality of life for premature infants are vitally important. This article comparatively analyzes and critiques five intervention studies of premature infants using tactile stimulation and provides future research directions in this area. By examining the effectiveness of the tactile stimulation studies, some evidence and guidance can be provided for researchers generating knowledge in this area as well as nurses involved in clinical care.
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Cuidado del Lactante/métodos , Recien Nacido Prematuro/crecimiento & desarrollo , Enfermería Neonatal/métodos , Tacto , Humanos , Recién Nacido , Estimulación FísicaAsunto(s)
Antiasmáticos/farmacología , Asma/fisiopatología , Flavonoides/farmacología , Ovalbúmina/inmunología , Tráquea/fisiopatología , 3',5'-AMP Cíclico Fosfodiesterasas/antagonistas & inhibidores , Algoritmos , Animales , AMP Cíclico/metabolismo , Conductividad Eléctrica , Electrofisiología , Inhibidores Enzimáticos/farmacología , Cobayas , Técnicas In Vitro , Masculino , Microscopía Electrónica de Rastreo , Perfusión , Permeabilidad/efectos de los fármacos , Factores de Tiempo , Tráquea/efectos de los fármacosRESUMEN
PURPOSE: To determine aortic endothelial cells permeation ability and mechanisms of the aqueous block copolymeric micelles, poly(ethylene oxide)-poly (beta-benzyl L-aspartate) (PEO-PBLA) chemically conjugated with fluroescein isothiocyanate (FITC) by transport study and confocal laser scanning microscopy. METHODS: The block copolymers' PEO-PBLA-FITC was first synthesized and characterized by gel permeation chromatography (GPC) reflect index, UV, fluorescence detectors, and critical micelles concentrations (CMC), and atomic force microscopy (AFM). Permeation ability and mechanisms of polymeric micelles in aortic endothelial cells were evaluated by incubating with NaF, NaN3, wortmannin, cytochalasin B inhibitors, at 20 degrees C, and under reverse conditions. FITC and latex particles (40 nm) were also used for comparison of transport ability. The extent of localization of uptake polymeric micelles was established by confocal laser scanning microscopy. RESULTS: The size of the aqueous PEO-PBLA-FITC polymeric micelles was detected at around 56 nm with unimodal distribution by AFM. The CMC test revealed the fluorescence intensity increased to around 0.01-0.05 mg/ml. NaF, NaN3, wortmannin, cytochalasin B, 20 degrees C, and reverse experiments inhibited the absorption of polymeric micelles through aortic endothelial cells with apparent permeability coefficients (P) of 18.07 +/- 1.03 to 12.98 +/- 0.93, 11.31 +/- 0.77, 12.44 +/- 1.23, 6.40 +/- 0.23, 11.11 +/- 0.46, and 10.22 +/- 1.09 x 10(-7) cm/sec, respectively. Also, the permeation of FITC and latex on aortic endothelial cells was 70.02 +/- 4.71, and 2.05 +/- 0.41 x 10(-7) cm/sec, respectively. Confocal laser microscopy showed that fluorescent compounds were distributed in the intracellular cytoplasm and nucleus. CONCLUSIONS: PEO-PBLA-FITC copolymeric micelles in an aqueous system were transported by energy-dependent endocytosis with 18.07 x 10(-7) cm/sec penetrated range and were localized on intracellular and nucleus endothelial cells.
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Permeabilidad de la Membrana Celular , Endotelio Vascular/metabolismo , Micelas , Polímeros/metabolismo , Animales , Aorta , Transporte Biológico , Bovinos , Endotelio Vascular/citología , Colorantes Fluorescentes , Isotiocianatos , Microscopía ConfocalRESUMEN
PURPOSE: To directly visualize and evaluate the aqueous block copolymeric micelles, poly(ethylene oxide)-poly(beta-benzyl L-aspartate) (PEO-PBLA) chemically conjugated with pyrene fluorescence molecule, by nanotechnology of atomic force microscopy (AFM). METHODS: The block copolymers' PEO-PBLA-Pyrene was first synthesized by reacting with pyrene sulfonyl chloride and PEO-PBLA in tetrahydrofuran (THF) solution and were identified by GPC reflect index, UV and fluorescence detectors. The characterization of physical and chemical properties of PEO-PBLA-Pyrene polymeric micellar solution were examined by the dynamic light scattering (DLS) and critical micelles concentrations (CMC). In addition, the nanotechnology of AFM was used to directly visualize the size and shape of nanopolymeric micelles. RESULTS: The pyrene fluorescence molecule were successfully conjugated at the amino group of the end of PBLA chain by GPC with three different detectors. The size of the aqueous PEO-PBLA-Pyrene polymeric micelles was detected around 57 nm with unimodal distribution by DLS measurement. As a result of this finding, the CMC test was also found out that the fluorescence intensity was increasing around 0.01 approximately 0.05 mg/ml. Using AFM evaluation of polymeric micellar solution, the morphology of aqueous PEO-PBLA-Pyrene polymeric micelles was observed on round shape and with the narrow dispersity of size range 50 approximately 80 nm. CONCLUSIONS: The presence of PEO-PBLA copolymers with pyrene in an aqueous system formed in a spherical and nano range of polymeric micelles.
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Microscopía de Fuerza Atómica , Péptidos/química , Polietilenglicoles/química , Polímeros/química , Pirenos/química , MicelasRESUMEN
Androgen excess and deficiency affect skeletal maturation and bone cell function. Understanding the molecular basis for these androgen effects could improve therapy/prevention of short stature and osteoporosis. Androgens act through binding to androgen receptors (ARs), which modulate gene transcription via interactions with DNA response elements on target genes. Because osteoblasts contain ARs at levels just below certain androgen-sensitive tissues, we sought to define the function of AR in a number of commonly used osteoblastic cell lines. Presence and quantification of AR protein and mRNA were evaluated by ligand binding assay, western blotting, and RNAse protection assay. AR-containing osteoblastic cell lines were exposed to nonaromatizable androgens and effects on gene expression were assessed. We found no evidence for direct effects of androgen on endogenous genes nor was androgen involved in modulation of parathyroid hormone effects on early gene activation. Androgen-sensitive reporter gene constructs were stimulated by androgen only when AR cDNA expression vectors were introduced into cells by cotransfection. We conclude that, in commonly used osteoblastic cell lines, the presence of AR at the levels described here does not guarantee androgen transcriptional activity. The effects of androgen on bone in vivo may involve direct stimulation of osteoblastic cells in a different setting or stage of differentiation. Alternatively, androgen may act on bone cells other than osteoblasts, or through metabolic conversion to estrogens.
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Andrógenos/farmacología , Osteoblastos/efectos de los fármacos , Receptores Androgénicos/metabolismo , Transcripción Genética/efectos de los fármacos , Andrógenos/metabolismo , Animales , Unión Competitiva , Northern Blotting , Western Blotting , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Línea Celular , Células Cultivadas , ADN/genética , ADN/metabolismo , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Genes Reporteros/efectos de los fármacos , Genes Reporteros/genética , Humanos , Masculino , Osteoblastos/citología , Osteoblastos/metabolismo , Osteosarcoma/metabolismo , Osteosarcoma/patología , Hormona Paratiroidea/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ensayo de Unión Radioligante , Receptores Androgénicos/efectos de los fármacos , Receptores Androgénicos/genética , Ribonucleasas/metabolismo , Transcripción Genética/genética , Activación Transcripcional , TransfecciónRESUMEN
Antioxidant enzymes together with trace elements in 26 patients with chronic renal failure treated with hemodialysis and 25 healthy subjects were investigated. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSHPx) in plasma and erythrocytes were examined immediately before and after hemodialysis. The results are summarized as follows: 1. A significant decrease in plasma SOD, CAT, and GSHPx and erythrocyte GSHPx were found in patients before hemodialysis. 2. Erythrocyte CAT and GSHPx were significantly lower in the patients after hemodialysis than in the controls. 3. Plasma GSHPx was significantly higher after a single hemodialysis than before hemodialysis. 4. A good correlation between erythrocyte SOD and copper (Cu) in patients before hemodialysis was found. 5. A good correlation of GSHPx in erythrocytes and plasma was found before hemodialysis, whereas an even better correlation was found after hemodialysis. 6. Abnormalities of trace elements were found in hemodialyzed patients. 7. There is indirect evidence for increased oxidizing stress in uremic patients with hemodialysis. Dialysis treatment may improve some abnormalities (e.g., Hb, P), but may also induce some deleterious effects of free radicals or lipid peroxidation.
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Antioxidantes/metabolismo , Estrés Oxidativo , Diálisis Renal , Oligoelementos/metabolismo , Adulto , Anciano , Análisis Químico de la Sangre , Catalasa/sangre , Eritrocitos/química , Femenino , Glutatión Peroxidasa/sangre , Humanos , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Análisis de Regresión , Diálisis Renal/efectos adversos , Superóxido Dismutasa/sangreRESUMEN
A combination of experimental and modeling approaches was used to study cellular-molecular mechanisms underlying the expression of short-term potentiation (STP) and long-term potentiation (LTP) of glutamatergic synaptic transmission in the hippocampal slice. Electrophysiological recordings from dentate granule cells revealed that high-frequency stimulation of perforant path afferents induced a robust STP and LTP of both (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptor-mediated synaptic responses. However, the decay time constant for STP of the AMPA receptor-mediated excitatory postsynaptic potential was approximately 6 min, whereas the decay time constant for STP of the NMDA receptor-mediated excitatory postsynaptic potential was only 1 min. In addition, focal application of agonists during the expression of STP revealed that the magnitude of conductance change elicited by NMDA application was significantly enhanced, whereas the magnitude of conductance change elicited by application of AMPA remained constant. These findings are most consistent with a postsynaptic mechanism of STP and LTP. Different putative mechanisms were evaluated formally using a computational model that included diffusion of glutamate within the synaptic cleft, different kinetic properties of AMPA and NMDA receptor/channels, and geometric relations between presynaptic release sites and postsynaptic receptor/channels. Simulation results revealed that the only hypothesis consistent with experimental data is that STP and LTP reflect a relocation of AMPA receptor/channels in the postsynaptic membrane such that they become more closely "aligned" with presynaptic release sites. The same mechanism cannot account for STP or LTP of NMDA receptor-mediated responses; instead, potentiation of the NMDA receptor subtype is most consistent with an increase in receptor sensitivity or number.
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Hipocampo/fisiología , Modelos Neurológicos , Transmisión Sináptica/fisiología , Animales , Electrofisiología , Terminales Presinápticos/fisiología , Conejos , Receptores AMPA/fisiología , Receptores de N-Metil-D-Aspartato/fisiología , Sinapsis/fisiologíaRESUMEN
Trace elements and lipid peroxidation in 26 patients with chronic renal failure treated with hemodialysis and 25 healthy subjects were observed. Both plasma and erythrocyte trace elements and plasma malon dialdehyde (MDA) were examined immediately before and after hemodialysis. Increased levels of plasma Cu, MDA, and erythrocyte Pb, Mn, Zn, and a significantly decreased plasma Se, Zn, and erythrocyte Se were found in patients before hemodialysis. After a single hemodialysis, erythrocyte Mn, Cu, Zn, and plasma Cu, Al, and MDA were significantly increased whereas both plasma and erythrocyte Se were lower in patients than in healthy subjects. The level of MDA was not significantly changed during the single hemodialysis. Both plasma and erythrocyte Zn levels and plasma Cu and Al were significantly higher after hemodialysis than before hemodialysis. In conclusion, levels of trace elements are altered by hemodialysis, which may increase patient susceptibility to lipid peroxidation in uremia.
Asunto(s)
Eritrocitos/metabolismo , Peroxidación de Lípido/fisiología , Diálisis Renal/efectos adversos , Oligoelementos/sangre , Uremia/sangre , Adulto , Anciano , Aluminio/sangre , Cobre/sangre , Femenino , Humanos , Hierro/sangre , Plomo/sangre , Masculino , Malondialdehído/sangre , Manganeso/sangre , Persona de Mediana Edad , Fósforo/sangre , Análisis de Regresión , Reproducibilidad de los Resultados , Selenio/sangre , Espectrofotometría Atómica , Uremia/terapia , Zinc/sangreRESUMEN
Presynaptic mechanisms influencing the probability of neurotransmitter release from an axon terminal, such as facilitation, augmentation, and presynaptic feedback inhibition, are fundamental features of biological neurons and are cardinal physiological properties of synaptic connections in the hippocampus. The consequence of these presynaptic mechanisms is that the probability of release becomes a function of the temporal pattern of action potential occurrence, and hence, the strength of a given synapse varies upon the arrival of each action potential invading the terminal region. From the perspective of neural information processing, the capability of dynamically tuning the synaptic strength as a function of the level of neuronal activation gives rise to a significant representational and processing power of temporal spike patterns at the synaptic level. Furthermore, there is an exponential growth in such computational power when the specific dynamics of presynaptic mechanisms varies quantitatively across axon terminals of a single neuron, a recently established characteristic of hippocampal synapses. During learning, alterations in the presynaptic mechanisms lead to different pattern transformation functions, whereas changes in the postsynaptic mechanisms determine how the synaptic signals are to be combined. We demonstrate the computational capability of dynamic synapses by performing speech recognition from unprocessed, noisy raw waveforms of words spoken by multiple speakers with a simple neural network consisting of a small number of neurons connected with synapses incorporating dynamically determined probability of release. The dynamics included in the model are consistent with available experimental data on hippocampal neurons in that parameter values were chosen so as to be consistent with time constants of facilitative and inhibitory processes governing the dynamics of hippocampal synaptic transmission studied using nonlinear systems analytic procedures.