RESUMEN
The bioactivity of anodized near-ß TiNbSn alloy with low Young's modulus prepared in sulfuric acid electrolytes was examined to explore the osseointegration mechanism with a focus on the role of anodic oxide. Hydroxyapatite (HA) precipitated on the surface of anodic oxide following immersion in Hank's solution, and precipitation accelerated with increase in the sulfuric acid concentration of the electrolyte. HA is formed on the surface of as-anodized oxide without subsequent annealing or hot water (HW) treatment. This outcome differs from that of a previous study using anodized TiNbSn alloy prepared in acetic acid electrolytes requiring for subsequent HW treatment. It was found that the oxide anodized in sulfuric acid electrolyte contains a large amount of internal pores and is highly crystallized thick TiO2, whereas the same prepared in the acetic acid electrolyte is low crystalline thin TiO2 containing a small amount of pores. The present anodized TiNbSn alloy is preferred for maintaining the low Young's modulus of the alloy and eliminating the subsequent treatment to increase the Young's modulus. A model to rationalize the bioactivity of the present anodic oxide is proposed based on the series of studies. It is concluded that the sulfuric acid electrolyte is favorable for both HA formation and low Young's modulus, and the bioactivity is attributed to the anodic TiO2 that facilitates incorporation of bone ingredients.
Asunto(s)
Aleaciones/química , Materiales Biocompatibles/química , Electrólitos , Ácidos Sulfúricos/químicaRESUMEN
The activity of Au nanoparticle-loaded P25 TiO2 (Au/P25) plasmonic photocatalysts, evaluated by the oxidative decomposition of formic acid in water under visible light irradiation, was enhanced up to 3 times by simply mixing Au/P25 with photocatalytically inactive h-BN nanosheets as a result of electron transfer from photoexcited Au/TiO2 to the h-BN nanosheets and retardation of the charge recombination.
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Complejo CD3/análisis , Antígenos CD4/análisis , Linfoma Cutáneo de Células T/inmunología , Células Neoplásicas Circulantes/inmunología , Neoplasias Cutáneas/inmunología , Diagnóstico Diferencial , Femenino , Humanos , Linfoma Cutáneo de Células T/patología , Persona de Mediana Edad , Prurigo/diagnóstico , Neoplasias Cutáneas/patología , Extremidad SuperiorAsunto(s)
Antineoplásicos/efectos adversos , Hidrocarburos Aromáticos con Puentes/efectos adversos , Células Endoteliales/metabolismo , Fibroblastos/metabolismo , Proteínas de Microfilamentos/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Esclerodermia Sistémica/inducido químicamente , Taxoides/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Esclerodermia Sistémica/metabolismo , Piel/metabolismo , TransactivadoresAsunto(s)
Albuminuria/genética , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Linfotoxina-alfa/genética , Anciano , Creatinina/sangre , ADN/genética , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Frecuencia de los Genes , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Polimorfismo Genético/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
We have investigated whether GH treatment influences the expression of UCP1, 2 and 3 mRNA in a KK-Ay obese mouse model. KK-Ay mice (n = 10) and C57Bl/6J control mice (n = 10) were injected subcutaneously with human GH (1.0 mg/kg/day and 3.5 mg/kg/day) for 10 days, and compared with mice injected with physical saline. The KK-Ay obese mice weighed significantly less (p < 0.01 : 1.0 mg/kg/day, p < 0.05 : 3.5 mg/kg/day) and had smaller inguinal subcutaneous and perimetric white adipose tissue (WAT) pads (p < 0.05 : 3.5 mg/kg/day), but increased skeletal muscle weight (p < 0.05). The brown adipose tissue (BAT) weight did not change significantly. Not only plasma free fatty acid and glucose levels but also plasma insulin levels decreased. The reduced HOMA-IR (homeostasis model assessment-insulin resistance) values suggested that insulin resistance was improved by GH treatment. UCP1 mRNA levels increased after the 3.5 mg GH treatment by 2.8-fold (p < 0.01 vs. saline controls) and 2.0-fold (p < 0.05 vs. 1 mg GH treatment) in BAT, and by 6.0-fold in subcutaneous WAT (p < 0.05 vs. controls). UCP2 mRNA levels increased 2.2-fold (p < 0.05 vs. control) and 2.1-fold (p < 0.05 vs. 1 mg GH treatment) in BAT, and 2.0-fold (p < 0.05 vs. controls) in skeletal muscle. One mg GH administration also stimulated UCP1 mRNA expression by 2.5-fold (p < 0.05 vs. controls) and UCP3 mRNA expression by 2.8-fold (p < 0.05 vs. controls) in the muscle. On the other hand, lean mice showed no significant difference in body composition or plasma parameters. UCP1, 2 and 3 mRNA expression in lean mice did not show any significant change after treatment with GH. We conclude that GH treatment increased mRNA levels for not only UCP1, but also UCP 2 and 3 in BAT, WAT and muscle in a KK-Ay obese mouse model. These findings suggest that GH-induced thermogenesis may contribute to the reduction in WAT and energy expenditure.
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Tejido Adiposo/metabolismo , Proteínas Portadoras/metabolismo , Hormona del Crecimiento/farmacología , Proteínas de la Membrana/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Músculo Esquelético/metabolismo , Obesidad/metabolismo , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Animales , Sangre/efectos de los fármacos , Proteínas Portadoras/genética , Femenino , Humanos , Canales Iónicos , Proteínas de la Membrana/genética , Proteínas de Transporte de Membrana/genética , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Proteínas Mitocondriales/genética , Músculo Esquelético/efectos de los fármacos , Obesidad/sangre , Obesidad/genética , Obesidad/patología , Tamaño de los Órganos/efectos de los fármacos , ARN Mensajero/metabolismo , Proteína Desacopladora 1 , Proteína Desacopladora 2 , Proteína Desacopladora 3Asunto(s)
Proteínas Portadoras/genética , Diabetes Mellitus Tipo 2/genética , Retinopatía Diabética/genética , Proteínas de Neoplasias , Polimorfismo Genético , Proteínas Supresoras de Tumor , Anciano , Índice de Masa Corporal , Proteína de Unión a los Ácidos Grasos 7 , Proteínas de Unión a Ácidos Grasos , Femenino , Fluoresceína-5-Isotiocianato , Colorantes Fluorescentes , Hemoglobina Glucada/análisis , Humanos , Japón , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Espectrometría de Fluorescencia , XantenosRESUMEN
OBJECTIVE: To test the hypothesis that nicotine not only activates uncoupling protein1 (UCP1) in brown adipose tissue (BAT), but also induces UCP1 in white adipose tissue (WAT), which contributes to the mitigation of obesity in obese mice. DESIGN: Weights of the whole body, the gastrocnemius muscle, interscapular BAT and subcutaneous and retroperitoneal WAT, food intake and the mRNA and protein of UCP1 in these tissues were measured and immunohistochemistry using antiserum against UCP1 was also performed in obese yellow KK mice treated with nicotine for 6 months and control mice treated with physiological saline. RESULTS: Obese mice treated with nicotine for 6 months, compared with those injected with saline, weighed significantly less (P < 0.01) and had smaller subcutaneous and retroperitoneal WAT pads (P < 0.01), while obese mice that received nicotine ate less (P < 0.05) than those injected with saline. In mice treated with nicotine, the mRNA and protein of UCP1 was detected not only in BAT, but also in subcutaneous and retroperitoneal WATs. Immunohistochemically, the BAT of obese mice contained large lipid droplets and appeared rather WAT-like, but changed to typical brown adipocytes after nicotine treatment. The fat pads of nicotine-treated mice contained many multilocular cells that were positive for UCP1. CONCLUSION: Nicotine not only activates UCP1 in BAT, but also induces UCP1 in WAT and decreases food intake, which contributes to the mitigation of obesity.
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Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Proteínas Portadoras/efectos de los fármacos , Estimulantes Ganglionares/farmacología , Proteínas de la Membrana/efectos de los fármacos , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Obesidad/metabolismo , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Animales , Western Blotting , Proteínas Portadoras/genética , Inmunohistoquímica , Canales Iónicos , Proteínas de la Membrana/genética , Ratones , Ratones Obesos , Proteínas Mitocondriales , ARN/análisis , Proteína Desacopladora 1RESUMEN
The recently described variant of the human beta3-adrenergic receptor (AR) gene located mainly in visceral adipocytes is associated with earlier onset of NIDDM, abdominal obesity, insulin resistance, and an increased capacity to gain weight. We investigated whether lipolysis in human omental adipocytes induced by a potent and selective human beta3-AR agonist (L-755,507) was affected by the Trp64Arg mutation of the beta3-adrenoceptor, using 18 omental fat samples obtained during total hysterectomy. The Trp64Arg mutation was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Arg64 homozygous (n = 4) had a lower median effective concentration (EC50) and lower responsiveness compared with wild-type (n = 8) (EC50: -6.55 +/- 0.21 vs. -7.53 +/- 0.35 log mol/l, P = 0.007; responsiveness: 3.48 +/- 0.32 vs. 5.76 +/- 0.36 micromol x 10(5) cells(-1) x 90 min(-1), P = 0.014, respectively), although there was no difference in lipolysis induced by isoproterenol or CGP12177. Trp64Arg heterozygous (n = 6) also had a significantly lower EC50 and lower responsiveness (EC50: -6.18 +/- 0.09 log mol/l; responsiveness: 4.17 +/- 0.33 micromol x 10(5) cells(-1) x 90 min(-1)). We concluded that the Trp64Arg mutation of the beta3-AR gene is associated with lower lipolytic activities.
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Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Agonistas Adrenérgicos beta/farmacología , Lipólisis/fisiología , Mutación/fisiología , Receptores Adrenérgicos beta/genética , Sulfonamidas/farmacología , Adulto , Secuencia de Aminoácidos/genética , Femenino , Humanos , Isoproterenol/farmacología , Persona de Mediana Edad , Mutación/genética , Epiplón , Propanolaminas/farmacologíaAsunto(s)
Proteínas Portadoras/genética , Proteínas de la Membrana/genética , Obesidad/genética , Obesidad/fisiopatología , Polimorfismo Genético , Receptores Adrenérgicos beta/genética , Pérdida de Peso/genética , Sustitución de Aminoácidos , Índice de Masa Corporal , Femenino , Tamización de Portadores Genéticos , Variación Genética , Homocigoto , Humanos , Canales Iónicos , Japón , Persona de Mediana Edad , Proteínas Mitocondriales , Oportunidad Relativa , Mutación Puntual , Receptores Adrenérgicos beta 3 , Valores de Referencia , Proteína Desacopladora 1Asunto(s)
Arginina/genética , Diabetes Mellitus Tipo 2/genética , Mutación Puntual , Receptores Adrenérgicos beta/genética , Triptófano/genética , Tejido Adiposo/metabolismo , Alelos , Animales , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Frecuencia de los Genes , Genotipo , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Insulina/administración & dosificación , Insulina/uso terapéutico , Resistencia a la Insulina/genética , Persona de Mediana Edad , ARN Mensajero/análisis , Ratas , Receptores Adrenérgicos beta 3RESUMEN
The mitochondrial uncoupling protein (UCP) has usually been found only in brown adipose tissue. We recently observed that a chronic administration of the beta 3-adrenergic agonist CL-316,243 (CL) induced the ectopic expression of UCP in white fat and skeletal muscle in genetic obese yellow KK mice. The aim of the present study was to examine whether UCP could be induced in nongenetic obese animals produced by neonatal injections of monosodium L-glutamate (MSG). The daily subcutaneous injection of CL (0.1 mg/kg) to MSG-induced obese mice for 2 wk caused significant reductions of body weight (15%) and white fat pad weight (58%). Northern and Western blot analyses showed that CL induced significant expressions of UCP in the white fat and muscle, as well as in brown fat. Immunohistochemical observations revealed that the UCP stains in white fat were localized on multilocular cells and that those in muscle were localized on slow-twitch fibers rich in mitochondria. Immunoelectron microscopy confirmed the mitochondrial localization of UCP in the myocytes. The guanosine 5'-diphosphate (GDP) binding to mitochondria in brown fat doubled after the CL treatment. Moreover, significant GDP binding was detected in the white fat and muscle of the CL-treated mice, at about one-fourth and one-thirteenth the activity of brown fat, respectively, suggesting that ectopically expressed UCP is functionally active. We concluded that the beta 3-adrenergic agonist CL can induce functionally active UCP in white fat and slow-twitch muscle fibers of obese mice.
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Tejido Adiposo/efectos de los fármacos , Agonistas Adrenérgicos beta/farmacología , Proteínas Portadoras/biosíntesis , Dioxoles/farmacología , Proteínas de la Membrana/biosíntesis , Fibras Musculares de Contracción Lenta/efectos de los fármacos , Receptores Adrenérgicos beta/metabolismo , Tejido Adiposo/metabolismo , Animales , Proteínas Portadoras/genética , Femenino , Aditivos Alimentarios/farmacología , Guanosina Difosfato/metabolismo , Canales Iónicos , Proteínas de la Membrana/genética , Ratones , Ratones Obesos , Microscopía Inmunoelectrónica , Mitocondrias Musculares/efectos de los fármacos , Mitocondrias Musculares/metabolismo , Proteínas Mitocondriales , Fibras Musculares de Contracción Lenta/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Obesidad/metabolismo , ARN Mensajero/metabolismo , Receptores Adrenérgicos beta/efectos de los fármacos , Receptores Adrenérgicos beta 3 , Glutamato de Sodio/farmacología , Proteína Desacopladora 1RESUMEN
The inhibitory effect of beta3-adrenoceptor agonists on the ob gene in brown adipose tissue (BAT) and white adipose tissue (WAT) is now well documented both in vivo in lean animals and in vitro, but the reported effects of beta3-adrenoceptor agonists on ob gene expression in obese animals remain controversial. We investigated whether ob gene expression in BAT and WAT is reduced by acute and chronic administrations of a beta3-adrenoceptor agonist, CL316,243 (CL). The ob gene mRNA levels in BAT, perimetric and inguinal WAT of obese Yellow KK mice were about 4-fold higher than those of lean controls. Acute exposure (6 h) to CL decreased ob gene mRNA levels in three fat depots in both animals. Chronic exposure (10 days) to CL also decreased ob gene mRNA levels in BAT, perimetric, and inguinal WAT in both animals. We concluded that acute and chronic regulation by a beta3-adrenoceptor agonist suppressed ob gene expression in obese Yellow KK mice and lean controls.
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Tejido Adiposo/efectos de los fármacos , Agonistas Adrenérgicos beta/farmacología , Dioxoles/farmacología , Obesidad/genética , Proteínas/genética , ARN Mensajero/análisis , Tejido Adiposo/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Regulación hacia Abajo , Ingestión de Alimentos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Leptina , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Tamaño de los Órganos/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the effects of Trp64Arg mutation in the beta 3-adrenergic receptor gene on weight loss, body fat distribution, glycemic control, and insulin resistance in obese type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We measured body weight, waist-to-hip ratio (WHR), adjusted resting metabolic rate, fasting blood glucose, fasting serum insulin levels, insulin resistance index (fasting glucose x fasting insulin/22.5), and HbA1c levels before and after 12 weeks of obesity treatment in 61 obese women with type 2 diabetes. The MvaI polymorphism of the beta 3-adrenergic receptor gene was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Of obese type 2 diabetic patients, those with the mutation (n = 24) had a higher WHR (P < 0.001), a lower adjusted metabolic rate, and higher blood glucose levels, serum insulin levels, insulin resistance index (P < 0.001), and HbA1c levels (P = 0.016). Furthermore, patients with the mutation had smaller decreases in body weight, WHR, insulin resistance index, and HbA1c levels after the weight-loss program compared with patients without the mutation (n = 37), even though food intake, exercise, and serum thyroid hormone levels were similar in both groups. CONCLUSIONS: These present findings show that the Trp64Arg allele of the beta 3-adrenergic receptor gene may predict difficulty in losing body weight, lowering WHR, and improving glycemic control and insulin resistance in obese patients with type 2 diabetes.
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Constitución Corporal/fisiología , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus/fisiopatología , Mutación/fisiología , Obesidad , Receptores Adrenérgicos beta/genética , Adulto , Alelos , Glucemia/análisis , Glucemia/genética , Constitución Corporal/genética , Diabetes Mellitus/genética , Diabetes Mellitus Tipo 2/genética , Ayuno/sangre , Femenino , Genotipo , Hemoglobina Glucada/análisis , Humanos , Insulina/sangre , Resistencia a la Insulina/fisiología , Persona de Mediana Edad , Mutación/genética , Reacción en Cadena de la Polimerasa , Polimorfismo Genético/genética , Receptores Adrenérgicos beta 3 , Pérdida de Peso/genética , Pérdida de Peso/fisiologíaRESUMEN
Proliferative diabetic retinopathy is an important cause of visual impairment. We investigated whether the polymorphism of the beta 3-adrenoreceptor (beta 3-AR) gene, which is associated with insulin resistance and an earlier onset of NIDDM, was associated with proliferative diabetic retinopathy (PDR) in 215 Japanese NIDDM patients with a duration of diabetes of > or = 10 years. The polymorphism of the beta 3-AR gene was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. The Trp64Arg allele of the beta 3-AR gene was significantly more frequent in the NIDDM patients with PDR (P = 0.002), but not in those with non-PDR (P = 0.151), than in NIDDM patients without diabetic retinopathy. Those with the mutation had an earlier onset of diabetes, a longer duration of diabetes, and higher current and maximal BMI values, compared with those without the mutation. Moreover, this mutation was also associated with higher serum triglyceride and decreased HDL-cholesterol levels. When adjustment was made for age, age at diagnosis, duration of diabetes, current BMI, systolic blood pressure, HbA1e, and serum lipids in a multiple regression analysis, a significant association was found between the Trp64Arg allele and diabetic retinopathy (P = 0.039). The Arg/Arg or Arg/Trp genotype was significantly associated with PDR, compared with the Trp/Trp genotype, with an odds ratio of 2.55 (95% CI 1.25-5.16). We concluded that the beta 3-AR gene polymorphism is a newly identified risk factor for PDR.