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1.
Artículo en Inglés | MEDLINE | ID: mdl-33029174

RESUMEN

BACKGROUND: Sailuotong (SLT) is a standardized three-herb formulation consisting of extracts of Panax ginseng, Ginkgo biloba, and Crocus sativus for the treatment of vascular dementia (VaD). Although SLT has been shown to increase cerebral blood flow, the direct effects of SLT on vascular reactivity have not been explored. This study aims to examine the vasodilatory effects of SLT and the underlying mechanisms in rat isolated tail artery. METHODS: Male (250-300 g) Wistar Kyoto (WKY) rat tail artery was isolated for isometric tension measurement. The effects of SLT on the influx of calcium through the cell membrane calcium channels were determined in Ca2+-free solution experiments. RESULTS: SLT (0.1-5,000 µg/ml) caused a concentration-dependent relaxation in rat isolated tail artery precontracted by phenylephrine. In the contraction experiments, SLT (500, 1,000, and 5,000 µg/mL) significantly inhibited phenylephrine (0.001 to 10 µM)- and KCl (10-80 mM)-induced contraction, in a concentration-dependent manner. In Ca2+-free solution, SLT (500, 1,000, and 5,000 µg/mL) markedly suppressed Ca2+-induced (0.001-3 mM) vasoconstriction in a concentration-dependent manner in both phenylephrine (10 µM) or KCl (80 mM) stimulated tail arteries. L-type calcium channel blocker nifedipine (10 µM) inhibited PE-induced contraction. Furthermore, SLT significantly reduced phenylephrine-induced transient vasoconstriction in the rat isolated tail artery. CONCLUSION: SLT induces relaxation of rat isolated tail artery through endothelium-independent mechanisms. The SLT-induced vasodilatation appeared to be jointly meditated by blockages of extracellular Ca2+ influx via receptor-gated and voltage-gated Ca2+ channels and inhibition of the release of Ca2+ from the sarcoplasmic reticulum.

2.
J Pharm Biomed Anal ; 169: 60-69, 2019 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-30836247

RESUMEN

Naoluoxintong decoction (NLXTD) is a traditional Chinese formula which has been used for the management of ischemic stroke in China for two hundred years. In this study, we developed a comprehensive and reliable analytical method to qualitatively analyze the components in NLXTD. This novel method was based on three-dimensional ultra-fast high performance liquid chromatography coupled with diode array detector (3D-UPLC-DAD) with an additional component validation method via incorporation of the mixture standard compounds during the verification step. In addition, the relationship between active components and "Monarch drug, Minster drug, Assistant drug, Guide drug" were determined. Our results showed that gradient elution with the mobile phase of 0.02% formic acid and methanol was the optimum condition to separate peaks. A total of 35 common peaks were established by comparing ten batches of NLXTD, and eight components were identified, including Calycosin, Calycosin-7-O-ß-d-glucoside and Ononin in Astragali radix (Monarch drug); Ligustrazine in Chuanxiong Rhizoma (Minster drug); 4-Hydroxbenzyl alcohol and Parishin A in Gastrodiae rhizome (Assistant drug); Ferulic acid in Angelicae sinensis radix (Guide drug). The validation method of verification by adding mixture standard compounds combined with 3D-UPLC-DAD method, with the merits of greater resolution, higher speed of analysis and higher sensitivity, provided a semi-quantitative and qualitative analysis method to assess traditional Chinese medicinal prescription consisting of many bio-active components. Finally, our study has provided systemic and scientific evidence to explain the relationship between the bio-active components in the NLXTD and traditional Chinese medicine theory.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Rizoma/química , China , Ácidos Cumáricos/química , Glucósidos/química , Isoflavonas/química , Medicina Tradicional China/métodos , Extractos Vegetales/química , Sensibilidad y Especificidad
3.
Int J Obstet Anesth ; 32: 11-16, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28501265

RESUMEN

BACKGROUND: We constructed an algorithm for the management of coagulopathy from massive postpartum hemorrhage. Fibrinogen concentrate was administered preferentially, and the dose of both fibrinogen concentrate and fresh frozen plasma given was determined by the plasma fibrinogen concentration and prothrombin time. The efficacy of the algorithm and the amount of fibrinogen concentrate and fresh frozen plasma transfused were determined. METHODS: The study was conducted in a single teaching perinatal center. Nineteen patients were included between April 2011 and March 2014 (patient group). For a historical comparison group, we retrospectively analyzed the records of 19 patients who had been treated for coagulopathy from massive postpartum hemorrhage between April 2006 and March 2011 (control group). RESULTS: Blood loss was significantly lower in the patient group. No adverse events were associated with this management in either group. The dose of fibrinogen concentrate administered was significantly higher and that of fresh frozen plasma administered was significantly lower in the patient group. CONCLUSION: This algorithm appeared to help reduce blood loss and the total amount of fresh frozen plasma transfused when treating coagulopathy from postpartum hemorrhage, and may represent another strategy for achieving hemostasis in this setting.


Asunto(s)
Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Fibrinógeno/uso terapéutico , Hemorragia Posparto/tratamiento farmacológico , Adulto , Algoritmos , Transfusión Sanguínea , Femenino , Fibrinógeno/efectos adversos , Humanos , Plasma , Embarazo , Estudios Retrospectivos
4.
Neuroscience ; 319: 92-106, 2016 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-26820596

RESUMEN

Dominant optic atrophy (DOA) arises from mutations in the OPA1 gene that promotes fusion of the inner mitochondrial membrane and plays a role in maintaining ATP levels. Patients display optic disc pallor, retinal ganglion cell (RGC) loss and bilaterally reduced vision. We report a randomized, placebo-controlled trial of idebenone at 2000 mg/kg/day in 56 Opa1 mutant mice (B6;C3-Opa1(Q285STOP)), with RGC dendropathy and visual loss, and 63 wildtype mice. We assessed cellular responses in the retina, brain and liver and RGC morphology, by diolistic labeling, Sholl analysis and quantification of dendritic morphometric features. Vision was assessed by optokinetic responses. ATP levels were raised by 0.57 nmol/mg (97.73%, p=0.035) in brain from idebenone-treated Opa1 mutant mice, but in the liver there was an 80.35% (p=0.011) increase in oxidative damage. NQO1 expression in Opa1 mutant mice was reduced in the brain (to 30.5%, p=0.002) but not in retina, and neither expression level was induced by idebenone. ON-center RGCs failed to show major recovery, other than improvements in secondary dendritic length (by 53.89%, p=0.052) and dendritic territory (by 2.22 × 10(4) µm(2) or 90.24%, p=0.074). An improvement in optokinetic response was observed (by 12.2 ± 3.2s, p=0.003), but this effect was not sustained over time. OFF-center RGCs from idebenone-treated wildtype mice showed shrinkage in total dendritic length by 2.40 mm (48.05%, p=0.025) and a 47.37% diminished Sholl profile (p=0.029). Visual function in wildtype idebenone-treated mice was impaired (2.9 fewer head turns than placebo, p=0.007). Idebenone appears largely ineffective in protecting Opa1 heterozygous RGCs from dendropathy. The detrimental effect of idebenone in wildtype mice has not been previously observed and raises some concerns.


Asunto(s)
Antioxidantes/farmacología , Atrofia Óptica Autosómica Dominante/patología , Células Ganglionares de la Retina/efectos de los fármacos , Ubiquinona/análogos & derivados , Agudeza Visual/efectos de los fármacos , Animales , Western Blotting , Dendritas/patología , Modelos Animales de Enfermedad , Femenino , GTP Fosfohidrolasas/genética , Inmunohistoquímica , Masculino , Ratones , Ratones Mutantes , Distribución Aleatoria , Células Ganglionares de la Retina/patología , Ubiquinona/farmacología
5.
Eur J Vasc Endovasc Surg ; 50(4): 466-73, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26188720

RESUMEN

OBJECTIVE/BACKGROUND: Recent genetic data suggest that a polymorphism of LRP1 is an independent risk factor for abdominal aortic aneurysm (AAA). The aims of this study were to assess whether plasma and aortic concentrations of low-density lipoprotein receptor-related protein 1 (LRP1) are associated with AAA, and to investigate the possible relevance of LRP1 to AAA pathophysiology. METHODS: Three analyses were conducted. First, plasma LRP1 concentrations were measured in community-dwelling men with and without AAA (n = 189 and n = 309, respectively) using enzyme-linked immunosorbent assay. Second, Western blotting analyses were employed to compare the expression of LRP1 protein in aortic biopsies collected from patients with AAA and nonaneurysmal postmortem donors (n = 6/group). Finally, the effect of in vitro LRP1 blockade on matrix metalloprotease 9 (MMP9) clearance by vascular smooth muscle cells was assessed by zymography. RESULTS: Plasma LRP1 concentrations did not differ between groups of men with and without AAA (median concentration 4.56 µg/mL [interquartile range {IQR} (3.39-5.96)] and 4.43 µg/mL [IQR 3.44-5.84], respectively; p = .48), and were not associated with AAA after adjusting for other risk factors (odds ratio 1.10 [95% confidence interval: 0.91-1.32]; p = 0.35). In contrast, LRP1 expression was approximately 3.4-fold lower in aortic biopsies recovered from patients with AAA compared with controls (median [IQR] expression 1.72 [0.94-3.14] and 5.91 [4.63-6.94] relative density units, respectively; p < .01). In vitro LRP1 blockade significantly reduced the ability of vascular smooth muscle cells to internalize extracellular MMP9. CONCLUSIONS: These data suggest that aortic but not circulating LRP1 is downregulated in patients with AAA and indicates a possible role for this protein in clearing an aneurysm-relevant ligand.


Asunto(s)
Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/sangre , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/sangre , Anciano , Anticuerpos/farmacología , Aorta Abdominal/efectos de los fármacos , Aneurisma de la Aorta Abdominal/diagnóstico , Biomarcadores/sangre , Biopsia , Western Blotting , Estudios de Casos y Controles , Células Cultivadas , Regulación hacia Abajo , Ensayo de Inmunoadsorción Enzimática , Humanos , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/antagonistas & inhibidores , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Oportunidad Relativa , Factores de Riesgo
6.
Int J Endocrinol ; 2015: 810439, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26060494

RESUMEN

Diabetes mellitus (DM) is a metabolic disorder affecting a large number of people worldwide. Numerous studies have demonstrated that DM can cause damage to multiple systems, leading to complications such as heart disease, cancer, and cerebrovascular disorders. Numerous epidemiological studies have shown that DM is closely associated with dementia and cognition dysfunction, with recent research focusing on the role of DM-mediated cerebrovascular damage in dementia. Despite the therapeutic benefits of antidiabetic agents for the treatment of DM-mediated cognitive dysfunction, most of these pharmaceutical agents are associated with various undesirable side-effects and their long-term benefits are therefore in doubt. Early evidence exists to support the use of traditional Chinese medicine (TCM) interventions, which tend to have minimal toxicity and side-effects. More importantly, these TCM interventions appear to offer significant effects in reducing DM-related complications beyond blood glucose control. However, more research is needed to further validate these claims and to explore their relevant mechanisms of action. The aims of this paper are (1) to provide an updated overview on the association between DM and cognitive dysfunction and (2) to review the scientific evidence underpinning the use of TCM interventions for the treatment and prevention of DM-induced cognitive dysfunction and dementia.

8.
Int J Tuberc Lung Dis ; 17(6): 818-24, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23676169

RESUMEN

SETTING: DosR regulon genes are considered essential for Mycobacterium tuberculosis dormancy, and their products are demonstrated to have immunogenicity in M. tuberculosis-infected individuals, suggesting that DosR regulon-encoded proteins are suitable targets for vaccines to control the reactivation of dormant M. tuberculosis. OBJECTIVE: Prospective analysis of T-cell and antibody responses against DosR regulon-encoded antigens in M. tuberculosis-infected individuals in Japan to identify effective vaccine targets. DESIGN: T-cell responses against 33 DosR regulon-encoded antigens were investigated in 26 consecutive M. tuberculosis-infected individuals--14 with latent tuberculosis infection (LTBI) and 12 with active pulmonary tuberculosis (PTB)--using enzyme-linked immunosorbent spot assay, and antibody responses in 42 consecutive individuals, 14 with LTBI and 28 with PTB. RESULT: Six antigens (Rv0570, Rv1996, Rv2004c, Rv2028c, Rv2029c and Rv3133c) induced stronger T-cell responses in LTBI than in PTB, In contrast, antigen-specific antibody responses to five antigens (Rv0080, Rv1738, Rv2007c, Rv2031c and Rv2032) were found to be stronger in PTB than in LTBI cases. CONCLUSION: T-cell responses to six antigens might contribute to natural protection against dormant M. tuberculosis. These antigens are therefore considered to be potential targets of novel vaccines to control M. tuberculosis reactivation in the Japanese population.


Asunto(s)
Antígenos Bacterianos/inmunología , Tuberculosis Latente/inmunología , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Formación de Anticuerpos/inmunología , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Proteínas de Unión al ADN , Ensayo de Immunospot Ligado a Enzimas , Femenino , Humanos , Japón , Tuberculosis Latente/genética , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/genética , Estudios Prospectivos , Proteínas Quinasas/genética , Proteínas Quinasas/inmunología , Regulón/genética , Regulón/inmunología , Linfocitos T/inmunología , Tuberculosis Pulmonar/genética
9.
Phytomedicine ; 16(5): 426-36, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19109000

RESUMEN

In this study, we evaluated the pharmacological effects of Ganoderma lucidum (G. lucidum) (water-extract) (0.003, 0.03 and 0.3g/kg, 4-week oral gavage) consumption using the lean (+db/+m) and the obese/diabetic (+db/+db) mice. Different physiological parameters (plasma glucose and insulin levels, lipoproteins-cholesterol levels, phosphoenolpyruvate carboxykinase (PEPCK), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) and isolated aorta relaxation of both species were measured and compared. G. lucidum (0.03 and 0.3g/kg) lowered the serum glucose level in +db/+db mice after the first week of treatment whereas a reduction was observed in +db/+m mice only fed with 0.3g/kg of G. lucidum at the fourth week. A higher hepatic PEPCK gene expression was found in +db/+db mice. G. lucidum (0.03 and 0.3g/kg) markedly reduced the PEPCK expression in +db/+db mice whereas the expression of PEPCK was attenuated in +db/+m mice (0.3g/kg G. lucidum). HMG CoA reductase protein expression (in both hepatic and extra-hepatic organs) and the serum insulin level were not altered by G. lucidum. These data demonstrate that G. lucidum consumption can provide beneficial effects in treating type 2 diabetes mellitus (T2DM) by lowering the serum glucose levels through the suppression of the hepatic PEPCK gene expression.


Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Proteínas Serina-Treonina Quinasas/metabolismo , Reishi , Grasa Abdominal/efectos de los fármacos , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Peso Corporal/efectos de los fármacos , Colesterol/sangre , Diabetes Mellitus Experimental/sangre , Ingestión de Energía/efectos de los fármacos , Hidroximetilglutaril-CoA Reductasas/metabolismo , Hipoglucemiantes/farmacología , Insulina/sangre , Lipólisis/efectos de los fármacos , Lipoproteínas/sangre , Ratones , Obesidad/tratamiento farmacológico , Extractos Vegetales/farmacología , Vasodilatación/efectos de los fármacos
10.
Prostaglandins Other Lipid Mediat ; 87(1-4): 62-7, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18812234

RESUMEN

Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by cytochrome P450 epoxygenases in endothelial cells. It has previously been shown that EETs activate K(+) channels, which are important for the hyperpolarization and dilation of blood vessels. However, the effects of EETs on other ion channels have been less well studied. We investigated the effects of EETs on volume-activated Cl(-) channels (VACCs) in rat mesenteric arterial smooth muscle cells. Whole-cell patch clamp recording demonstrated that hypotonic solution and guanosine 5'-[gamma-thio]triphosphate (GTPgammaS) induced a 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB)- and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)-sensitive VACC current in the primary cultured rat mesenteric arterial smooth muscle cells. The VACC current was inhibited by EETs and the order of potency was 8,9-EET>5,6-EET>11,12-EET>14,15-EET. The inhibitory effects of EETs could be reversed by 14,15 epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, an EET analog), Rp-cGMP and KT-5823 (protein kinase G inhibitors). Interestingly, the inhibitory effects of EETs on VACCs were not influenced by Rp-cAMP (a protein kinase A antagonist) but it could be abolished by NF-449 (a Gs protein inhibitor), indicating the involvement of cAMP but not protein kinase A. In conclusion, our results demonstrate that EETs inhibit VACCs in rat mesenteric arterial smooth muscle cells through a cGMP-dependent pathway, which is probably due to the cross-activation by cAMP. This mechanism may be involved in the regulation of cell volume and membrane potential.


Asunto(s)
Ácido 8,11,14-Eicosatrienoico/farmacología , Canales de Cloruro/metabolismo , Arterias Mesentéricas/citología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Animales , Masculino , Arterias Mesentéricas/efectos de los fármacos , Arterias Mesentéricas/metabolismo , Ratas , Ratas Sprague-Dawley
11.
J Dent Res ; 87(1): 51-5, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18096893

RESUMEN

Butyric acid, an extracellular metabolite from periodontopathic bacteria, induces apoptosis in murine and human T- and B-cells, whereas intact gingival fibroblasts isolated from healthy humans are resistant to butyric-acid-induced apoptosis. We examined the susceptibility of inflamed gingival fibroblasts isolated from adult persons with periodontitis to butyric-acid-induced apoptosis. Butyric acid significantly suppressed the viability of inflamed gingival fibroblasts and induced apoptosis in a dose-dependent manner. The incubation of inflamed gingival fibroblasts with butyric acid induced DNA fragmentation and apoptotic changes such as chromatin condensation, hypodiploid nuclei, and mitochondrial injury. Furthermore, butyric-acid-induced apoptosis in inflamed gingival fibroblasts was reduced by caspase-3/7, -6, -8, and -9 inhibitors. Thus, inflamed gingival fibroblasts from adult persons with periodontitis appear to be highly susceptible to mitochondria- and caspase-dependent apoptosis induced by butyric acid, compared with healthy gingival fibroblasts.


Asunto(s)
Apoptosis/efectos de los fármacos , Ácido Butírico/farmacología , Fibroblastos/efectos de los fármacos , Encía/patología , Periodontitis/patología , Adulto , Ácido Butírico/administración & dosificación , Inhibidores de Caspasas , Núcleo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cromatina/efectos de los fármacos , Fragmentación del ADN , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos
12.
Arch Orthop Trauma Surg ; 128(1): 11-5, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17203284

RESUMEN

Low-grade central osteosarcoma is an unusual variant of conventional osteosarcoma. We present here two rare cases of low-grade central osteosarcoma resembling fibrous dysplasia. A 24-year-old woman diagnosed as fibrous dysplasia was treated with intra-lesional excision and curettage of the tumor but tumor recurred at 4 months after surgery. Distal femoral en-bloc resection was performed followed by arthroplasty with mega-prosthesis of the knee. A 57-year-old man diagnosed as central osteosarcoma was treated with wide excision of the tumor, followed by reconstruction with the vascularized fibula graft combined with an autogenous irradiated bone graft. Because of the difficulty in distinguishing low-grade central osteosarcoma from a benign lesion, open biopsy is needed to obtain a large tumor sample. Careful clinical and pathological evaluation is required to obtain a definite diagnosis. The treatment of low-grade central osteosarcoma is en-block resection with wide surgical margins.


Asunto(s)
Neoplasias Óseas/diagnóstico , Neoplasias Femorales/diagnóstico , Displasia Fibrosa Ósea/diagnóstico , Osteosarcoma/diagnóstico , Tibia , Adulto , Neoplasias Óseas/cirugía , Diagnóstico Diferencial , Femenino , Neoplasias Femorales/cirugía , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Osteosarcoma/patología , Osteosarcoma/cirugía
13.
Acta Neurochir (Wien) ; 149(9): 897-902; discussion 902, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17690837

RESUMEN

BACKGROUND: High rates of overall- and event-free survival have been reported in patients with intracranial germinoma treated by radiotherapy. We report the long-term results after treatment initially with chemotherapy, but without radiation. PATIENTS AND METHOD: Five patients with an intracranial germinoma were treated with 2 cycles of etoposide and cisplatin, without radiotherapy. All achieved complete remission; 3 suffered recurrence within 2 years and were again treated with 2 cycles of etoposide and cisplatin followed by radiotherapy. RESULTS: At long-term follow-up, each of the 5 patients was in complete remission without further recurrence. Each patient with a neurohypophyseal germinoma who presented with endocrinopathy had initially recovered endocrinological function. CONCLUSION: In a patient with a germinoma chemotherapy, and restriction of radiation to those with recurrence may allow restoration of hypophyseal function damaged by the intracranial germinoma without compromising long term survivial.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Cisplatino/uso terapéutico , Etopósido/uso terapéutico , Germinoma/tratamiento farmacológico , Adolescente , Enfermedades de los Ganglios Basales/tratamiento farmacológico , Neoplasias Encefálicas/diagnóstico , Niño , Enfermedades del Sistema Endocrino/etiología , Enfermedades del Sistema Endocrino/fisiopatología , Femenino , Germinoma/complicaciones , Germinoma/diagnóstico , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Glándula Pineal , Neurohipófisis/fisiopatología , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/tratamiento farmacológico , Recuperación de la Función , Inducción de Remisión , Retratamiento
14.
Br J Pharmacol ; 151(7): 987-97, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17558433

RESUMEN

BACKGROUND AND PURPOSE: Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase inhibitors) have been demonstrated to reduce cardiovascular mortality. It is unclear how the expression level of HMG CoA reductase in cardiovascular tissues compares with that in cells derived from the liver. We hypothesized that this enzyme exists in different cardiovascular tissues, and simvastatin modulates the vascular iberiotoxin-sensitive Ca2+-activated K(+) (BK(Ca)) channels. EXPERIMENTAL APPROACHES: Expression of HMG CoA reductase in different cardiovascular preparations was measured. Effects of simvastatin on BK(Ca) channel gatings of porcine coronary artery smooth muscle cells were evaluated. KEY RESULTS: Western immunoblots revealed the biochemical existence of HMG CoA reductase in human cardiovascular tissues and porcine coronary artery. In porcine coronary artery smooth muscle cells, extracellular simvastatin (1, 3 and 10 microM) (hydrophobic), but not simvastatin Na+ (hydrophilic), inhibited the BK(Ca) channels with a minimal recovery upon washout. Isopimaric acid (10 microM)-mediated enhancement of the BK(Ca) amplitude was reversed by external simvastatin. Simvastatin Na+ (10 microM, applied internally), markedly attenuated isopimaric acid (10 microM)-induced enhancement of the BK(Ca) amplitude. Reduced glutathione (5 mM; in the pipette solution) abolished simvastatin -elicited inhibition. Mevalonolactone (500 microM) and geranylgeranyl pyrophosphate (20 microM) only prevented simvastatin (1 and 3 microM)-induced responses. simvastatin (10 microM ) caused a rottlerin (1 microM)-sensitive (cycloheximide (10 microM)-insensitive) increase of PKC-delta protein expression. CONCLUSIONS AND IMPLICATIONS: Our results demonstrated the biochemical presence of HMG CoA reductase in different cardiovascular tissues, and that simvastatin inhibited the BK(Ca) channels of the arterial smooth muscle cells through multiple intracellular pathways.


Asunto(s)
Músculo Liso Vascular/efectos de los fármacos , Péptidos/farmacología , Canales de Potasio Calcio-Activados/antagonistas & inhibidores , Simvastatina/farmacología , Adulto , Anciano , Animales , Western Blotting , Caveolina 1/biosíntesis , Línea Celular , Línea Celular Tumoral , Vasos Coronarios/citología , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/fisiología , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Imidazoles/farmacología , Técnicas In Vitro , Masculino , Potenciales de la Membrana/efectos de los fármacos , Persona de Mediana Edad , Músculo Liso Vascular/citología , Músculo Liso Vascular/fisiología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/fisiología , Ésteres del Forbol/farmacología , Canales de Potasio Calcio-Activados/metabolismo , Canales de Potasio Calcio-Activados/fisiología , Proteína Quinasa C-delta/metabolismo , Piridinas/farmacología , Simvastatina/química , Porcinos
15.
Eur J Pharmacol ; 546(1-3): 109-19, 2006 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-16908017

RESUMEN

We evaluated the acute effect of homocysteine on the iberiotoxin-sensitive, Ca(2+)-activated K(+) (BK(Ca)) channels of the porcine coronary artery smooth muscle cells. NS 1619 (1 to 30 microM) caused a concentration-dependent enhancement of the BK(Ca) amplitude (recorded using the whole-cell, membrane-rupture configuration) only with an elevated [Ca(2+)](i) of approximately 444 nM, but not with [Ca(2+)](i) of approximately 100 nM. Homocysteine (30 microM) caused a small inhibition ( approximately 16%) of the BK(Ca) amplitude ([Ca(2+)](i)= approximately 444 nM), and a greater inhibition ( approximately 77%) was observed with 100 microM NADH present in the pipette solution. The inhibition persisted after washing. With NADPH (100 microM), a smaller magnitude of inhibition ( approximately 34%) of the BK(Ca) amplitude was recorded. The NS 1619-mediated enhancement of the BK(Ca) amplitude (with elevated [Ca(2+)](i) plus NADH in the pipette) was attenuated by homocysteine. The homocysteine-mediated inhibition of the BK(Ca) amplitude was suppressed by Tiron (10 mM) or diphenylene iodonium (30 nM), applied alone, but not by superoxide dismutase (500 U/ml) and catalase (500 U/ml). Generation of superoxide (O(2)(-)) of the smooth muscle cells (with NADH presence), measured using the lucigenin-enhanced chemiluminescence, was markedly increased by angiotensin II (100 nM) and homocysteine (30 microM). The chemiluminescence signal was sensitive to apocynin (300 microM) or Tiron, applied alone, but not to superoxide dismutase and catalase. In conclusion, our results demonstrate that acute homocysteine application inhibits the iberiotoxin-sensitive BK(Ca) channels (with elevated [Ca(2+)](i) and NADH present) which is probably caused by the NADH oxidase activation and the concomitant generation of intracellular superoxide.


Asunto(s)
Homocisteína/farmacología , Músculo Liso Vascular/efectos de los fármacos , Péptidos/farmacología , Bloqueadores de los Canales de Potasio/farmacología , Canales de Potasio Calcio-Activados/efectos de los fármacos , Sal Disódica del Ácido 1,2-Dihidroxibenceno-3,5-Disulfónico/farmacología , Acetofenonas/farmacología , Angiotensina II/farmacología , Animales , Bencimidazoles/farmacología , Calcio/metabolismo , Vasos Coronarios/citología , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/metabolismo , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Homocisteína/análogos & derivados , Técnicas In Vitro , Activación del Canal Iónico/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , NAD/metabolismo , NADPH Oxidasas/antagonistas & inhibidores , NADPH Oxidasas/metabolismo , Técnicas de Placa-Clamp , Canales de Potasio Calcio-Activados/metabolismo , Superóxidos/metabolismo , Porcinos , Vasoconstrictores/farmacología
16.
Eur J Pediatr ; 165(7): 484-8, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16552544

RESUMEN

We describe two previously healthy children who had multiple ecchymoses several days after acute infection. In both cases, the prothrombin time (PT) and the activated partial thromboplastin time (APTT) were prolonged. Further examinations revealed the presence of lupus anticoagulant (LA), phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT), and low serum complement. In both cases, we confirmed the presence of a serum immune complex. The patients' symptoms improved spontaneously within 1 week, and all laboratory data normalized within several months. We also describe another asymptomatic case positive for LA and aPS/PT presumably associated with cytomegalovirus infection. The prevalence of transient antiphospholipid antibodies associated with viral infections in children must be much higher than we expected. We have to take it into consideration when we see abnormal coagulation results, but the occurrence of significant bleeding symptoms is rare.


Asunto(s)
Anticuerpos Antifosfolípidos/sangre , Infecciones/sangre , Enfermedad Aguda , Niño , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lactante , Inhibidor de Coagulación del Lupus/sangre , Masculino , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina
17.
AIDS Care ; 14(5): 651-64, 2002 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12419115

RESUMEN

The purpose of this study is to find out how HIV-infected haemophiliacs were informed and notified of their HIV infection. Self-reporting questionnaires were mailed to approximately 500 patients, about one half of the haemophiliac patients with HIV in Japan. The response rate was about 57% (n=283); and 270 (male=269) patients, apart from secondary and tertiary infected patients, were eligible as subjects for the study. The mean age was 31.2 +/- 9.9 years. Of these subjects, approximately 60% did not receive explanation regarding the risk of HIV infection via unheated blood products. More than 60% did not receive notification until 1990, or five years after the test became available in Japan. Contents of the explanations being given at the time of notifications were poor. In this paper, some problems of notifications of medically induced HIV are discussed, and the lack or delay of explanation/notification is concluded to be a consequence of the paternalistic attitudes of Japanese physicians and the iatrogenic nature of HIV infection.


Asunto(s)
Revelación/normas , Infecciones por VIH/diagnóstico , Hemofilia A/complicaciones , Adolescente , Adulto , Actitud del Personal de Salud , Transfusión Sanguínea , Familia , Femenino , Infecciones por VIH/transmisión , Hemofilia A/terapia , Humanos , Japón , Masculino , Relaciones Médico-Paciente , Factores de Riesgo , Factores de Tiempo
18.
Phys Rev E Stat Nonlin Soft Matter Phys ; 65(5 Pt 2): 057101, 2002 May.
Artículo en Inglés | MEDLINE | ID: mdl-12059754

RESUMEN

A one-dimensional irreversible adsorption-desorption process is simulated. The critical parameters as well as the critical exponents are measured. At the critical point, the crossover between the accumulative state and the depleted state is described by a universal characteristic function.

19.
Int J Obes Relat Metab Disord ; 26(7): 961-8, 2002 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12080450

RESUMEN

OBJECTIVE: We examined which of body mass index (BMI, kg/m(2)), serum cholesterol (mg/dl), or systolic blood pressure (SBP, mm Hg) affected age at natural menopause. DESIGN: A population-based follow-up program. METHODS: We determined the age at natural menopause in 1136 women followed biennially since their first examination in 1958-1959 through the 16th examination in 1988-1989. Four-hundred and ninety-three naturally menopausal women were classified into three groups by BMI, serum cholesterol and SBP measurement levels at age 40 or 41 y: the upper 25%, middle 50%, and lower 25%. We then studied whether there was a difference in age at menopause among the three groups thus classified. The 1136 natural menopausal women were also classified as early (n=454; 45-49 y at menopause (48.3+/-1.2 y)) or late (n=682; >or=50 y at menopause (52.3+/-1.6 y)) menopausal and compared for premenopausal trends in BMI, serum cholesterol and SBP in the early and late menopausal women by means of a longitudinal data analysis model. RESULTS: When women were classified into the three groups based on a BMI that was measured at 40 or 41 y, age at menopause in the upper 25% (50.4+/-2.8 y) was significantly higher (P<0.05) than that in the lower 25% (49.7+/-2.8 y). The entire premenopausal trend in BMI in late menopausal women shifted upward compared to that in early menopausal women. On the other hand, the premenopausal trend more than 4 y before menopause in serum cholesterol and the entire premenopausal trend in SBP in late menopausal women were identical to those in early menopausal women. CONCLUSION: Among the variables studied, only BMI is related to age at menopause, and the greater the BMI, the later the age at menopause.


Asunto(s)
Envejecimiento , Índice de Masa Corporal , Menopausia , Adulto , Presión Sanguínea , Colesterol/sangre , Femenino , Humanos , Persona de Mediana Edad , Modelos Biológicos
20.
Hypertens Res ; 24(4): 337-43, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11510744

RESUMEN

The relation between fatty liver, detected by ultrasonography as a marker of visceral fat accumulation, and coronary risk factors was studied in 810 elderly men and 1,273 elderly women in Nagasaki, Japan from 1990 to 1992. The prevalence of fatty liver was 3.3% in the male and 3.8% in the female non-obese participants (BMI, body mass index < 26.0 kg/m2) and 21.6% in the male and 18.8% in the female obese participants (26.0 kg/m2 < or = BMI). Fatty liver was significantly (p < 0.01) related to hypercholesterolemia and hypertriglyceridemia in the men and to hypertension, hypercholesterolemia, low-HDL cholesterol, hypertriglyceridemia and diabetes mellitus or impaired glucose tolerance (DM+IGT) in the women independent of age, obesity, smoking and drinking. Non-obesity with fatty liver, rather than obesity with or without fatty liver, had the highest odds ratio for hypertension and low-HDL cholesterol in the men and for hypercholesterolemia, low-HDL cholesterol, hypertriglyceridemia and DM+IGT in the women. The prevalence of fatty liver is the same in elderly men and women, and fatty liver is an independent correlate of coronary risk factors in the elderly.


Asunto(s)
Envejecimiento/fisiología , Pueblo Asiatico , Enfermedad Coronaria/etiología , Hígado Graso/diagnóstico por imagen , Anciano , Hígado Graso/complicaciones , Hígado Graso/epidemiología , Femenino , Humanos , Hiperlipidemias/complicaciones , Hipertensión/etiología , Japón/epidemiología , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Prevalencia , Factores de Riesgo , Distribución por Sexo , Ultrasonografía
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