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1.
Acta Physiol (Oxf) ; 219(1): 22-96, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-26706498

RESUMEN

The endothelium can evoke relaxations of the underlying vascular smooth muscle, by releasing vasodilator substances. The best-characterized endothelium-derived relaxing factor (EDRF) is nitric oxide (NO) which activates soluble guanylyl cyclase in the vascular smooth muscle cells, with the production of cyclic guanosine monophosphate (cGMP) initiating relaxation. The endothelial cells also evoke hyperpolarization of the cell membrane of vascular smooth muscle (endothelium-dependent hyperpolarizations, EDH-mediated responses). As regards the latter, hydrogen peroxide (H2 O2 ) now appears to play a dominant role. Endothelium-dependent relaxations involve both pertussis toxin-sensitive Gi (e.g. responses to α2 -adrenergic agonists, serotonin, and thrombin) and pertussis toxin-insensitive Gq (e.g. adenosine diphosphate and bradykinin) coupling proteins. New stimulators (e.g. insulin, adiponectin) of the release of EDRFs have emerged. In recent years, evidence has also accumulated, confirming that the release of NO by the endothelial cell can chronically be upregulated (e.g. by oestrogens, exercise and dietary factors) and downregulated (e.g. oxidative stress, smoking, pollution and oxidized low-density lipoproteins) and that it is reduced with ageing and in the course of vascular disease (e.g. diabetes and hypertension). Arteries covered with regenerated endothelium (e.g. following angioplasty) selectively lose the pertussis toxin-sensitive pathway for NO release which favours vasospasm, thrombosis, penetration of macrophages, cellular growth and the inflammatory reaction leading to atherosclerosis. In addition to the release of NO (and EDH, in particular those due to H2 O2 ), endothelial cells also can evoke contraction of the underlying vascular smooth muscle cells by releasing endothelium-derived contracting factors. Recent evidence confirms that most endothelium-dependent acute increases in contractile force are due to the formation of vasoconstrictor prostanoids (endoperoxides and prostacyclin) which activate TP receptors of the vascular smooth muscle cells and that prostacyclin plays a key role in such responses. Endothelium-dependent contractions are exacerbated when the production of nitric oxide is impaired (e.g. by oxidative stress, ageing, spontaneous hypertension and diabetes). They contribute to the blunting of endothelium-dependent vasodilatations in aged subjects and essential hypertensive and diabetic patients. In addition, recent data confirm that the release of endothelin-1 can contribute to endothelial dysfunction and that the peptide appears to be an important contributor to vascular dysfunction. Finally, it has become clear that nitric oxide itself, under certain conditions (e.g. hypoxia), can cause biased activation of soluble guanylyl cyclase leading to the production of cyclic inosine monophosphate (cIMP) rather than cGMP and hence causes contraction rather than relaxation of the underlying vascular smooth muscle.


Asunto(s)
Endotelio Vascular/fisiopatología , Músculo Liso Vascular/fisiopatología , Enfermedades Vasculares/fisiopatología , Animales , GMP Cíclico/metabolismo , Endotelina-1/metabolismo , Endotelio Vascular/metabolismo , Humanos , Músculo Liso Vascular/metabolismo , Óxido Nítrico/metabolismo , Enfermedades Vasculares/metabolismo , Vasoconstricción/fisiología , Vasodilatación/fisiología
4.
Cell Tissue Res ; 347(2): 369-81, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22287040

RESUMEN

This is the first detailed report about the collar enamel of the teeth of Polypterus senegalus. We have examined the fine structure of the collar enamel and enamel organ of Polypterus during amelogenesis by light and transmission electron microscopy. An immunohistochemical analysis with an antibody against bovine amelogenin, an antiserum against porcine amelogenin and region-specific antibodies or antiserum against the C-terminus, middle region and N-terminus of porcine amelogenin has also been performed to examine the collar enamel matrix present in these teeth. Their ameloblasts contain fully developed Golgi apparatus, rough endoplasmic reticulum and secretory granules. During collar enamel formation, an amorphous fine enamel matrix containing no collagen fibrils is found between the dentin and ameloblast layers. In non-demineralized sections, the collar enamel (500 nm to 1 µm thick) is distinguishable from dentin, because of its higher density and differences in the arrangement of its crystals. The fine structural features of collar enamel in Polypterus are similar to those of tooth enamel in Lepisosteus (gars), coelacanths, lungfish and amphibians. The enamel matrix shows intense immunoreactivity to the antibody and antiserum against mammalian amelogenins and to the middleregion- and C-terminal-specific anti-amelogenin antibodies. These findings suggest that the proteins in the enamel of Polypterus contain domains that closely resemble those of bovine and porcine amelogenins. The enamel matrix, which exhibits positive immunoreactivity to mammalian amelogenins, extends to the cap enameloid surface, implying that amelogenin-like proteins are secreted by ameloblasts as a thin matrix layer that covers the cap enameloid after enameloid maturation.


Asunto(s)
Esmalte Dental/química , Diente/química , Amelogénesis , Amelogenina/química , Amelogenina/metabolismo , Secuencia de Aminoácidos , Animales , Calcificación Fisiológica , Esmalte Dental/ultraestructura , Proteínas del Esmalte Dental/análisis , Proteínas de Peces/análisis , Proteínas de Peces/química , Proteínas de Peces/metabolismo , Peces/metabolismo , Inmunohistoquímica , Microscopía Electrónica de Transmisión , Datos de Secuencia Molecular , Diente/ultraestructura
5.
Scand J Surg ; 100(3): 153-8, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22108741

RESUMEN

BACKGROUND AND AIMS: The widespread use of high resolution computed tomography has increased the number of small peripheral lung cancers. This study reviewed the clinicopathological features of the patients with non-small cell lung cancer (NSCLC) with a tumor diameter of 1 cm or less, in order to explore the adequate management of such small sized lung cancers. MATERIAL AND METHODS: This study was a retrospective analysis of consecutive 58 patients (5.3% out of 1095 patients) who underwent a complete resection for a peripheral NSCLC with a diameter of 1.0 cm or less. The clinical features and outcomes were compared with 203 patients with NSCLC with a diameter between 1.1 and 2.0 cm. RESULTS: The mean age was 64.5 years and there were 26 males and 32 females. Clinical stage was IA in 57 (98%) and IIIA in 1. Lobectomy was performed in 39 patients, segmentectomy in nine, and nonanatomic wedge resection in ten. Two patients, who underwent systemic lymph node dissection, had mediastinal lymph node metastasis and were diagnosed as pathological stage IIIA; however they did not relapse after surgery. One patient with pathological stage IA papillary adenocarcinoma died due to brain metastases. The five-year overall survival rate and disease free survival rate was 95.0% and 95.3%, respectively. Patients with NSCLC of 1.0 cm or less showed significantly better survival than those with tumors measuring 1.1-2.0 cm in size (p = 0.048). DISCUSSION: The indications for avoiding systemic lymph node dissection for operable NSCLC should not be based on the size of the tumor. A small-sized lung cancer might be surgically treated before the tumor enlarges to more than 1.0 cm in size.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Distribución de Chi-Cuadrado , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Estadísticas no Paramétricas , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
7.
Eur Surg Res ; 47(4): 211-7, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22025080

RESUMEN

AIMS: This study retrospectively investigated the clinical significance of lymphovascular invasion (LVI) following a complete resection for stage I non-small cell lung cancer (NSCLC). METHODS: A total of 226 patients who underwent a complete resection for pathological stage I NSCLC were examined. RESULTS: Lymphatic invasion was pathologically diagnosed as ly0 in 156 patients, ly1 in 65, and ly2 in 5 patients. The pathological vascular invasion was diagnosed as v0 in 178 patients, v1 in 35, v2 in 10, and v3 in 3 patients. The 5-year survival rate after surgery of the patients with and without lymphatic invasion was 76.8 and 90.6%, respectively. There was a significantly more unfavorable prognosis in patients with lymphatic invasion (p = 0.042). The 5-year survival rate of the patients with vascular invasion was also significantly more unfavorable (67.8%) than that of patients without vascular invasion (90.4%; p = 0.004). LVI was found to significantly correlate with tumor size and the presence of pleural invasion. CONCLUSION: The LVI of NSCLC is a significant prognostic factor in patients with stage I tumors. In future clinical trials, it is necessary to evaluate the efficacy of adjuvant therapy for the selection of patients according to this criterion.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Adulto , Anciano , Anciano de 80 o más Años , Vasos Sanguíneos/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Japón/epidemiología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Metástasis Linfática , Vasos Linfáticos/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Adulto Joven
8.
Eur J Vasc Endovasc Surg ; 42(2): 254-60, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21454105

RESUMEN

OBJECTIVE: Lymphoedema is a common complication after cancer treatment. We have reported that low-energy extracorporeal shock wave (SW) therapy up-regulates vascular endothelial growth factor (VEGF) in ischaemic myocardium. As VEGF plays an important role in lymphangiogenesis, we investigated whether our low-energy SW therapy enhances lymphangiogenesis in rats. METHODS: We created a tail model of lymphoedema in rats. The tail was treated with or without low-energy SW therapy (0.25 mJ mm(-2), 500 impulses) four times (days 3, 5, 7, and 9). The tail volume and the fluorescence intensity of indocyanine green (ICG) were measured. The expression of VEGF-C and basic fibroblast growth factor (bFGF) were evaluated by RT-PCR, and the lymphatic vessel density was assessed histochemically. RESULTS: The tail volume increased significantly in the control group and was significantly improved in the SW group. The lymphatic system function (evaluated with fluorescence intensity of ICG), the lymphatic vessel density, and the expression of VEGF-C and bFGF were all enhanced by the SW therapy (all P < 0.05). CONCLUSIONS: The low-energy SW therapy induces therapeutic lymphangiogenesis by up-regulating VEGF-C and bFGF, and improves lymphoedema in a rat-tail model, suggesting that low-energy SW therapy could be a non-invasive and effective strategy for lymphoedema in humans.


Asunto(s)
Linfangiogénesis , Sistema Linfático/fisiopatología , Linfedema/terapia , Terapia por Ultrasonido , Animales , Modelos Animales de Enfermedad , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Sistema Linfático/metabolismo , Linfedema/genética , Linfedema/metabolismo , Linfedema/fisiopatología , Masculino , ARN Mensajero , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Albúmina Sérica/metabolismo , Factores de Tiempo , Regulación hacia Arriba , Factor C de Crecimiento Endotelial Vascular/genética , Factor C de Crecimiento Endotelial Vascular/metabolismo
9.
Acta Physiol (Oxf) ; 196(2): 193-222, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19220204

RESUMEN

The endothelium can evoke relaxations (dilatations) of the underlying vascular smooth muscle, by releasing vasodilator substances. The best characterized endothelium-derived relaxing factor (EDRF) is nitric oxide (NO). The endothelial cells also evoke hyperpolarization of the cell membrane of vascular smooth muscle (endothelium-dependent hyperpolarizations, EDHF-mediated responses). Endothelium-dependent relaxations involve both pertussis toxin-sensitive G(i) (e.g. responses to serotonin and thrombin) and pertussis toxin-insensitive G(q) (e.g. adenosine diphosphate and bradykinin) coupling proteins. The release of NO by the endothelial cell can be up-regulated (e.g. by oestrogens, exercise and dietary factors) and down-regulated (e.g. oxidative stress, smoking and oxidized low-density lipoproteins). It is reduced in the course of vascular disease (e.g. diabetes and hypertension). Arteries covered with regenerated endothelium (e.g. following angioplasty) selectively loose the pertussis toxin-sensitive pathway for NO release which favours vasospasm, thrombosis, penetration of macrophages, cellular growth and the inflammatory reaction leading to atherosclerosis. In addition to the release of NO (and causing endothelium-dependent hyperpolarizations), endothelial cells also can evoke contraction (constriction) of the underlying vascular smooth muscle cells by releasing endothelium-derived contracting factor (EDCF). Most endothelium-dependent acute increases in contractile force are due to the formation of vasoconstrictor prostanoids (endoperoxides and prostacyclin) which activate TP receptors of the vascular smooth muscle cells. EDCF-mediated responses are exacerbated when the production of NO is impaired (e.g. by oxidative stress, ageing, spontaneous hypertension and diabetes). They contribute to the blunting of endothelium-dependent vasodilatations in aged subjects and essential hypertensive patients.


Asunto(s)
Endotelio Vascular/fisiopatología , Enfermedades Vasculares/fisiopatología , Animales , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiología , Humanos , Modelos Biológicos , Enfermedades Vasculares/metabolismo , Vasoconstricción/fisiología , Vasodilatación/fisiología
10.
J Dent Res ; 87(2): 159-63, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18218843

RESUMEN

Endogenous insulin-like growth factor-I (IGF-I) is known to affect the growth and development of condylar cartilage. However, the critical effect of IGF-I on cell survival is still unknown. We hypothesized that endogenous IGF-I could regulate the survival of cells of the mandibular condylar cartilage. Mandibular condyles dissected from 12-day-old rats were cultured for 1, 3, and 5 days in medium containing antisense oligodeoxynucleotide (AS-ODN) for IGF-I. Real-time RT-PCR analysis showed that the levels of IGF-I and IGF binding protein (IGFBP)3 mRNAs in the AS-ODN group were significantly decreased. After 3 days' culture, the number of necrotic cells was observed in the undifferentiated mesenchymal cell layer. These cells were TUNEL-positive and confirmed to be apoptotic by electron microscopic observation. Immunoblotting revealed that expression of cleaved caspase3 was increased with AS-ODN. These results may suggest that the cells in the undifferentiated mesenchymal cell layer of the mandibular condyle require IGF-I for survival.


Asunto(s)
Apoptosis/fisiología , Cartílago/citología , Factor I del Crecimiento Similar a la Insulina/fisiología , Cóndilo Mandibular/citología , Animales , Caspasa 3/análisis , Diferenciación Celular , Supervivencia Celular/fisiología , Immunoblotting , Etiquetado Corte-Fin in Situ , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/análisis , Mesodermo/citología , Microscopía Electrónica , Necrosis , Oligodesoxirribonucleótidos Antisentido/farmacología , Técnicas de Cultivo de Órganos , Reacción en Cadena de la Polimerasa , Ratas , Ratas Sprague-Dawley
11.
Gene Ther ; 14(19): 1425-33, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17671509

RESUMEN

In the transplant surgery, reactive oxygen species (ROS) from the reperfused tissue cause ischemia-reperfusion injury, resulting in the primary graft failure. We have recently reported that Rho-kinase, an effecter of the small GTPase Rho, plays an important role in the ROS production in the hyperacute phase of reperfusion; however, the sources and mechanisms of the ROS production remain to be elucidated. The aim of this study was to investigate the source of ROS production with a special reference to Rho-kinase to develop a new strategy against ischemia-reperfusion injury. In an in vivo rat model of liver transplantation, Kupffer cells in the graft were depleted using liposome-encapsulated dichloromethylene diphosphonate to examine the source of ROS production. The effect of adenoviral-mediated overexpression of a dominant-negative Rho-kinase (AdDNRhoK) in hepatocytes in the graft was also examined. Kupffer cells were not involved in the ROS production, whereas the AdDNRhoK transfection to hepatocytes significantly suppressed the ROS production. Furthermore, the ROS production was dose-dependently inhibited by apocynin, an NADPH oxidase inhibitor. Expression of DNRhoK also suppressed the release of pro-inflammatory cytokines, and ameliorated the lethal liver injury with a significant prolongation of the survival. These results suggest that the Rho-kinase-mediated pathway plays a crucial role in the ROS production through NADPH oxidase in hepatocytes during the hyperacute phase of reperfusion in vivo. Thus, Rho-kinase in hepatocytes may be a new therapeutic target for the prevention of primary graft failure in liver transplantation.


Asunto(s)
Terapia Genética/métodos , Hepatocitos/metabolismo , Trasplante de Hígado , NADPH Oxidasas/antagonistas & inhibidores , Daño por Reperfusión/prevención & control , Quinasas Asociadas a rho/genética , Acetofenonas/uso terapéutico , Enfermedad Aguda , Adenoviridae/genética , Animales , Frío , Inhibidores Enzimáticos/uso terapéutico , Expresión Génica , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Supervivencia de Injerto , Hepatocitos/inmunología , Hepatocitos/patología , Interleucina-1/análisis , Interleucina-1/inmunología , Circulación Hepática , Masculino , Modelos Animales , NADPH Oxidasas/metabolismo , Ratas , Ratas Endogámicas BN , Especies Reactivas de Oxígeno/análisis , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/inmunología , Daño por Reperfusión/metabolismo , Transducción Genética/métodos , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/inmunología , Quinasas Asociadas a rho/antagonistas & inhibidores , Quinasas Asociadas a rho/metabolismo
12.
Acta Physiol (Oxf) ; 189(3): 221-31, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17305702

RESUMEN

AIM: Chronic cardiac unloading causes a time-dependent upregulation of phospholamban (PLB) and depression of myocyte contractility in normal rat hearts. As thyroid hormone is known to decrease PLB expression, we examined whether thyroid hormone restores the depressed contractile performance of myocytes from chronically unloaded hearts. METHODS: Cardiac unloading was induced by heterotopic heart transplantation in isogenic rats for 5 weeks. Animals were treated with either vehicle or physiological treatment dose of 3,5,3'-triiodo-L-thyronine (T3) that does not cause hyperthyroidism for the last 3 weeks (n=20 each). RESULTS: In vehicle-treated animals, myocyte relaxation and [Ca2+]i decay were slower in unloaded hearts than in recipient hearts. Myocyte shortening in response to high [Ca2+]o was also depressed with impaired augmentation of peak-systolic [Ca2+]i in unloaded hearts compared with recipient hearts. In vehicle-treated rats, protein levels of PLB were increased by 136% and the phosphorylation level of PLB at Ser16 were decreased by 32% in unloaded hearts compared with recipient hearts. By contrast, in the T3-treated animals, the slower relaxation, delayed [Ca2+]i decay, and depressed contractile reserve in myocytes from unloaded hearts were all returned to normal levels. Furthermore, in the T3-treated animals, there was no difference either in the PLB protein level or in its Ser16-phosphorylation level between unloaded and recipient hearts. CONCLUSION: These results suggest that the treatment with physiological treatment dose of thyroid hormone rescues the impaired myocyte relaxation and depressed contractile reserve at least partially through the restoration of PLB protein levels and its phosphorylation state in chronically unloaded hearts.


Asunto(s)
Calcio/metabolismo , Cardiomegalia/tratamiento farmacológico , Contracción Miocárdica/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Triyodotironina/uso terapéutico , Animales , Proteínas de Unión al Calcio/metabolismo , Cardiomegalia/metabolismo , Trasplante de Corazón , Masculino , Miocitos Cardíacos/efectos de los fármacos , Fosforilación , Distribución Aleatoria , Ratas , Ratas Endogámicas Lew , Trasplante Isogénico
15.
Bone ; 35(5): 1059-68, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15542030

RESUMEN

Recently, the involvement of immune responses in metabolic bone disease and/or local bone destruction has received much attention. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a member of the immunoglobulin (Ig) superfamily, negatively regulates T cell activation. The deficiency of CTLA-4 induces profound osteopenia with an increase in osteoclastogenesis, suggesting the important role of activated T cells in osteoclastogenesis. Programmed death-1 (PD-1) is the newly identified immunoregulatory receptor, which also belongs to the Ig superfamily. Both CTLA-4 and PD-1 are induced on activated T cells, however, there are no reports linking PD-1 with osteoclasts. In the present study, we have examined the bone phenotype in PD-1-deficient mice PD-1-/- and the role of PD-1 in osteoclastogenesis and osteoclast function. Both trabecular and cortical bone mineral densities of tibia were significantly increased, as observed in peripheral quantitative computed tomography (pQCT), at 12 weeks of age in PD-1-/- mice. Histomorphometric analysis of the PD-1-/- mice and the age-matched controls at 12 weeks of age showed a 2-fold increase in bone volume (BV/TV) with a 55% decrease in osteoclast number (N.Oc/BS). Bone formation indices were similar in both groups. The number of soluble receptor activator of nuclear factor kappaB ligand (sRANKL)-induced osteoclast-like cells (OCLs) derived from the PD-1-deficient splenocytes was significantly decreased (by 25%). On the other hand, PD-1 deficiency did not affect the bone-resorbing activity of mature osteoclasts. Our results suggest that PD-1 deficiency reduces osteoclastogenesis resulting in an osteopetrotic phenotype. Identical members of the Ig superfamily, CTLA-4 and PD-1, which negatively regulate immune responses, may differentially affect osteoclastogenesis and bone remodeling.


Asunto(s)
Antígenos de Superficie/genética , Osteoclastos/patología , Osteopetrosis/genética , Animales , Antígenos de Superficie/fisiología , Proteínas Reguladoras de la Apoptosis , Densidad Ósea/genética , Células de la Médula Ósea/química , Células de la Médula Ósea/metabolismo , Diferenciación Celular/genética , Expresión Génica/genética , Macrófagos/química , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Osteoblastos/química , Osteoblastos/metabolismo , Osteoclastos/química , Osteoclastos/metabolismo , Osteopetrosis/sangre , Fenotipo , Receptor de Muerte Celular Programada 1 , Tibia/patología
16.
Bone ; 31(4): 472-8, 2002 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12398942

RESUMEN

Matrix metalloproteinase-9 (MMP-9, or gelatinase B) is an extracellular proteinase that is highly expressed in osteoclasts and has been postulated to play an important role in their resorptive activity. Although MMP-9 has been reported to play a role in bone resorption, the association of this enzyme during deciduous tooth resorption has not yet been clarified. The purpose of the present study was to increase our understanding of the role of MMP-9 during deciduous tooth resorption. Reverse transcription-polymerase chain reaction (RT-PCR) and northern blot analysis of total RNAs extracted from bovine root-resorbing tissues, which lie between the root of a deciduous tooth and its permanent successor, revealed the expression of mRNA for MMP-9 in the tissue. These results indicate that MMP-9 may be involved in the process of deciduous tooth resorption. In addition, in situ hybridization and immunohistochemistry were also performed to identify the cells that produced MMP-9 in bovine root-resorbing tissue. MMP-9 mRNA was highly expressed in odontoclasts that were aligned along the surface of the tissue. Immunohistochemistry confirmed the predominant localization of MMP-9 in odontoclasts. The present data demonstrate that odontoclasts in deciduous root resorption express MMP-9, which may participate in proteolysis during root resorption of deciduous tooth.


Asunto(s)
Metaloproteinasa 9 de la Matriz/genética , Osteoclastos/enzimología , ARN Mensajero/genética , Resorción Dentaria , Diente Primario , Animales , Secuencia de Bases , Bovinos , Cartilla de ADN , Inmunohistoquímica , Hibridación in Situ , Metaloproteinasa 9 de la Matriz/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
17.
Calcif Tissue Int ; 70(2): 127-33, 2002 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11870419

RESUMEN

Cathepsin K is a cysteine proteinase, which is abundantly and selectively expressed in osteoclasts. It is believed to play an important role in the proteolysis of bone resorption by osteoclasts. The objectives of this study were to investigate the association of cathepsin K in the physiological root resorption of deciduous teeth and to identify the cathepsin K-producing cells in deciduous root resorption. RT-PCR and Northern blot analysis of the total RNAs extracted from bovine active and resting root-resorbing tissues, which lie between the root of deciduous tooth and its permanent successor, were performed. The active root-resorbing tissue, which has a high population of odontoclasts on its surface that is attached to resorbing root surface, showed an extremely high expression of cathepsin K in comparison with the resting root-resorbing tissue. By in situ hybridization, cathepsin K mRNA was highly and selectively expressed in multinucleated odontoclasts that aligned along the surface of the tissue and apposed to the resorbing root surface of the deciduous tooth. Western blot analysis of the active root-resorbing tissue was used to characterize the anti-cathepsin K antibody. A band of 27 kDa, corresponding with the predicted size for mature cathepsin K, was demonstrated. Immunohistochemistry confirmed the specific localization of cathepsin K protein to the odontoclasts. These results demonstrate that odontoclasts in the deciduous root resorption express cathepsin K mRNA and protein that may participate in the proteolysis of root resorption of the deciduous tooth.


Asunto(s)
Catepsinas/genética , Incisivo/enzimología , Osteoclastos/enzimología , Resorción Dentaria/enzimología , Diente Primario/enzimología , Animales , Northern Blotting , Western Blotting/métodos , Catepsina K , Catepsinas/biosíntesis , Bovinos , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
18.
Adv Space Res ; 30(4): 783-8, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12530366

RESUMEN

Hypergravity (2G) exposure elevated the nociceptive threshold (pain suppression) concomitantly with evoked neuronal activity in the hypothalamus. Young Wistar male rats were exposed to 2G by centrifugal rotation for 10 min. Before and after 2G exposure, the nociceptive threshold was measured as the withdrawal reflex by using the von Frey type needle at a total of 8 sites of each rat (nose, four quarters, upper and lower back, tail), and then rats were sacrificed. Fos expression was examined immunohistochemically in the hypothalamic slices of the 2G-treated rats. When rats were exposed to 2G hypergravity, the nociceptive threshold was significantly elevated to approximately 150 to 250% of the 1G baseline control levels in all the examination sites. The 2G hypergravity remarkably induced Fos expression in the paraventricular and arcuate nuclei of the hypothalamus. The analgesic effects of 2G hypergravity were attenuated by naloxone pretreatment. Data indicate that hypergravity induces analgesic effects in rats, mediated through hypothalamic neuronal activity in the endogenous opioid system and hypothalamo-pituitary-adrenal axis.


Asunto(s)
Hipergravedad , Hipotálamo/metabolismo , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Umbral del Dolor/fisiología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Animales , Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Núcleo Arqueado del Hipotálamo/metabolismo , Conducta Animal , Centrifugación , Hipotálamo/efectos de los fármacos , Masculino , Umbral del Dolor/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/metabolismo , Ratas , Ratas Wistar , Factores de Tiempo
19.
Hypertension ; 38(6): 1307-10, 2001 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-11751708

RESUMEN

Rho-kinase plays an important role in modulating Ca(2+) sensitivity of vascular smooth muscle and has been suggested to be involved in the increased systemic vascular resistance in hypertensive animals. However, it remains to be examined whether this is also the case in patients with essential hypertension. Recently, it has been shown that fasudil is a specific Rho-kinase inhibitor. The aim of this study was to examine whether Rho-kinase is involved in the pathogenesis of hypertension in humans by using this Rho-kinase inhibitor. Studies were performed in hypertensive patients (HT group, n=14) and age-matched normotensive subjects (NT group, n=12). Forearm blood flow was measured by a strain-gauge plethysmograph during intra-arterial infusion of graded doses of fasudil (3.2, 6.4, 12.8, and 25.6 microg/min) or sodium nitroprusside (0.4, 0.8, 1.6, and 3.2 microg/min). Resting forearm vascular resistance was significantly higher in the HT group than in the NT group (22+/-4 versus 17+/-5 U, respectively; P<0.05). The extent of the increase in forearm blood flow evoked by fasudil was significantly greater in the HT group than in the NT group (12.3+/-1.4 versus 6.0+/-0.6 mL. min(-1). 100 mL(-1), respectively; P<0.01). The percent decrease in forearm vascular resistance was significantly greater in the HT group than in the NT group (63.6+/-4.7% versus 29.6+/-3.9%, respectively; P<0.01). By contrast, forearm vasodilator response evoked by sodium nitroprusside was comparable between the 2 groups. These results provide the first evidence that Rho-kinase may be involved in the pathogenesis of the increased peripheral vascular resistance in hypertension in humans.


Asunto(s)
1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , Hipertensión/enzimología , Proteínas Serina-Treonina Quinasas/metabolismo , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Inhibidores Enzimáticos/farmacología , Femenino , Antebrazo/irrigación sanguínea , Humanos , Hipertensión/fisiopatología , Péptidos y Proteínas de Señalización Intracelular , Masculino , Persona de Mediana Edad , Músculo Liso Vascular , Nitroprusiato/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Flujo Sanguíneo Regional/efectos de los fármacos , Resistencia Vascular/efectos de los fármacos , Resistencia Vascular/fisiología , Vasodilatación/efectos de los fármacos , Quinasas Asociadas a rho
20.
Arterioscler Thromb Vasc Biol ; 21(12): 1896-901, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11742861

RESUMEN

3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, so-called statins, reduce the relative risk of a major coronary event by lowering the serum cholesterol level. In addition, statins may confer beneficial effects by cholesterol-lowering independent mechanisms, which are incompletely characterized. Because angiotensin II (Ang II) plays crucial roles in the pathogenesis of cardiovascular diseases, we examined the effect of statins on the expression of the Ang II type 1 receptor (AT(1)-R) in cultured vascular smooth muscle cells (VSMCs). Cerivastatin and fluvastatin reduced the AT(1)-R mRNA and the AT(1)-R protein levels; however, pravastatin lacked this effect. Cerivastatin and fluvastatin suppressed the AT(1)-R promoter activity measured by luciferase assay but did not affect AT(1)-R mRNA stability, suggesting that the suppression occurs at the transcriptional level. Coincubation of VSMCs with mevalonate or geranylgeranyl pyrophosphate but not with farnesyl pyrophosphate reversed the cerivastatin-induced AT(1)-R downregulation. Overexpression of dominant-negative Rho A also suppressed AT(1)-R mRNA expression. Treatment with cerivastatin for 24 hours reduced the calcium response of VSMCs to Ang II. Taken together, statins downregulate AT(1)-R expression through a mevalonate-dependent, geranylgeranyl pyrophosphate-dependent, and Rho A-dependent manner and attenuate the biological function of Ang II. Downregulation of AT(1)-R may contribute to the cholesterol-independent beneficial effect of statins on the cardiovascular system.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Músculo Liso Vascular/metabolismo , Receptores de Angiotensina/efectos de los fármacos , Animales , Sitios de Unión/efectos de los fármacos , Células Cultivadas , Regulación hacia Abajo , Ácidos Grasos Monoinsaturados/farmacología , Fluvastatina , Expresión Génica/efectos de los fármacos , Indoles/farmacología , Ácido Mevalónico/farmacología , Piridinas/farmacología , ARN Mensajero/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptor de Angiotensina Tipo 1 , Receptores de Angiotensina/genética , Receptores de Angiotensina/metabolismo
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