Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Más filtros












Base de datos
Intervalo de año de publicación
1.
Zhonghua Nan Ke Xue ; 29(2): 113-119, 2023 Feb.
Artículo en Chino | MEDLINE | ID: mdl-37847082

RESUMEN

OBJECTIVE: To analyze the effects of lncRNA SNHG12 on the proliferation, migration and invasiveness of PCa cells by regulating the expression of E2F5. METHODS: Using real time fluorescence RT-PCR, we detected the expressions of lncRNA SNHG12 and E2F5, constructed the PC3 cells inhibiting the lncRNA SNHG12 expression. After transfection of the PC3 cells, we divided them into an NC, a si-NC, a si-SNHG12, a si-E2F5, a si-SNHG12+OE-si-NC, and a si-SNHG12+OE-E2F5 group, followed by examination of the proliferation, apoptosis, migration and invasiveness of the cells in different groups. RESULTS: The expressions of lncRNA SNHG12 and E2F5 were significantly up-regulated in the PCa tissue compared with those in the adjacent tissue (P < 0.05), remarkably higher in the DU145, LNCaP and PC3 groups than in the RWPE-1 group, the highest in the PC3 group (P < 0.05). The expression of SNHG12 was markedly down-regulated in the si-SNHG12 group (P < 0.05) in comparison with that in the si-NC group, indicating the successful construction of a PC3 cell line interfering with the lncRNA SNHG12 expression. Compared with the si-NC group, the si-SNHG12 group showed significant decreases in the values of CyclinD1, MMP-9 and OD and the numbers of migrating and invading cells, and an increase in apoptotic cells (P < 0.05), while the si-E2F5 group exhibited a remarkably down-regulated expression of E2F5 (P < 0.05), reduced values of CyclinD1, MMP-9 and OD, decreased numbers of migrating and invading cells and an increased number of apoptotic cells (P < 0.05). The dual luciferase report test showed that E2F5 reduced the luciferase activity of SNHG12 (P < 0.05 and had an insignificant impact on the luciferase activity of MUT-SNHG12 (P > 0.05). Inhibiting the expression of lncRNA SNHG12 resulted in significant decreases in the expression of E2F5, values of CyclinD1, MMP-9 and OD and numbers of migrating and invading cells, but an increase in apoptotic cells (P < 0.05). The E2F5 expression, the CyclinD1, MMP-9 and OD values and the numbers of migrating and invading cells were markedly increased while the number of apoptotic cells decreased in the si-SNHG12+OE-E2F5 group compared with those in the si-SNHG12+OE-si-NC group (P < 0.05). CONCLUSION: Interfering with the expression of lncRNA SNHG12 can regulate that of E2F5, inhibit the proliferation, migration and invasiveness of PCa cells and promote their apoptosis.


Asunto(s)
MicroARNs , Neoplasias de la Próstata , ARN Largo no Codificante , Masculino , Humanos , ARN Largo no Codificante/genética , Metaloproteinasa 9 de la Matriz/genética , Movimiento Celular/genética , Proliferación Celular , Línea Celular Tumoral , Neoplasias de la Próstata/genética , Apoptosis/genética , Regulación Neoplásica de la Expresión Génica , Luciferasas/genética , MicroARNs/genética , Factor de Transcripción E2F5/genética
2.
J Med Chem ; 65(24): 16589-16621, 2022 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-36455032

RESUMEN

Small molecule inhibitors that target the phosphatidylinositol 3-kinase (PI3K) signaling pathway have received significant interest for the treatment of cancers. The class I isoform PI3Kα is most commonly associated with solid tumors via gene amplification or activating mutations. However, inhibitors demonstrating both PI3K isoform and mutant specificity have remained elusive. Herein, we describe the optimization and characterization of a series of benzoxazepin-oxazolidinone ATP-competitive inhibitors of PI3Kα which also induce the selective degradation of the mutant p110α protein, the catalytic subunit of PI3Kα. Structure-based design informed isoform-specific interactions within the binding site, leading to potent inhibitors with greater than 300-fold selectivity over the other Class I PI3K isoforms. Further optimization of pharmacokinetic properties led to excellent in vivo exposure and efficacy and the identification of clinical candidate GDC-0077 (inavolisib, 32), which is now under evaluation in a Phase III clinical trial as a treatment for patients with PIK3CA-mutant breast cancer.


Asunto(s)
Neoplasias de la Mama , Fosfatidilinositol 3-Quinasas , Humanos , Femenino , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasa Clase I/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Mutación
4.
J Orthop Surg Res ; 14(1): 357, 2019 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-31718690

RESUMEN

PURPOSE: To compare the time return to work and long-term results of tendoscopic versus open technique for de Quervain's disease. METHODS: From 2005 to 2013, either tendoscopic or open decompression was performed on 56 consecutive patients (56 wrists) with symptomatic de Quervain's disease despite a minimum of 3 months non-operative treatment. Of the 50 patients who met the inclusion criteria, 41 patients were followed-up for a mean of 7.21 years postoperatively. Among these 41 wrists, 20 underwent tendoscopic release (group A), and 21 underwent open release (group B). The clinical evaluations were performed preoperatively, 1 month postoperatively and at last follow-up visit, using visual analog scale (VAS); the Disabilities of the Arm, Shoulder and Hand (DASH) Outcome score; and the Finkelstein's test. The Patient and Observer Scar Assessment Scale (POSAS) was used as an esthetic evaluation tool of the scar at last follow-up. RESULTS: No significant baseline differences were found between two groups. The average time return to work in group A was less than in group B (P < 0.05), The mean VAS and DASH scores improved significantly in both groups at 1 month and last follow-up visit (P < 0.001). At 1 month, the scores in group A were significantly better than in group B (P < 0.05 and P < 0.001, respectively). There was no difference between groups at last follow-up. In addition, the improvement of the mean DASH score was significantly greater in group A than in group B (34.74 ± 10.99 in group A and 23.58 ± 12.01 in group B, P < 0.01) at 1 month. For POSAS scale, both the OSAS and PSAS scores were significantly better in group A. One patient in group A had cephalic vein injury and 3 patients in group B was involved with radial sensory nerve injury. All patients showed negative on Finkelstein's test at last follow-up. CONCLUSIONS: The results of this study suggest that tendoscopic technique for de Quervain's disease could provide earlier symptom relief and earlier recovery with fewer complications and more desirable scar, as well as equivalent successful long-term outcome, when compared with traditional open release technique.


Asunto(s)
Enfermedad de De Quervain/cirugía , Descompresión Quirúrgica/métodos , Adulto , Endoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
5.
Mar Biotechnol (NY) ; 21(3): 384-395, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30863905

RESUMEN

Body color is an interesting economic trait in fish. Red tilapia with red blotches may decrease its commercial values. Conventional selection of pure red color lines is a time-consuming and labor-intensive process. To accelerate selection of pure lines through marker-assisted selection, in this study, double-digest restriction site-associated DNA sequencing (ddRAD-seq) technology was applied to genotype a full-sib mapping family of Malaysia red tilapia (Oreochromis spp.) (N = 192). Genome-wide significant quantitative trait locus (QTL)-controlling red blotches were mapped onto two chromosomes (chrLG5 and chrLG15) explaining 9.7% and 8.2% of phenotypic variances by a genome-wide association study (GWAS) and linkage-based QTL mapping. Six SNPs from the chromosome chrLG5 (four), chrLG15 (one), and unplaced supercontig GL831288-1 (one) were significantly associated to the red blotch trait in GWAS analysis. We developed nine microsatellite markers and validated significant correlations between genotypes and blotch data (p < 0.05). Our study laid a foundation for exploring a genetic mechanism of body colors and carrying out genetic improvement for color quality in tilapia.


Asunto(s)
Pigmentación/genética , Sitios de Carácter Cuantitativo/genética , Tilapia/genética , Animales , Acuicultura , Cruzamiento , Estudio de Asociación del Genoma Completo , Fenotipo
6.
Mar Biotechnol (NY) ; 21(2): 250-261, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30737627

RESUMEN

Understanding the genetic mechanism of osmoregulation is important for the improvement of salt tolerance in tilapia. In our previous study, we have identified a major quantitative trait locus (QTL) region located at 23.0 Mb of chrLG18 in a Nile tilapia line by QTL-seq. However, the conservation of these QTLs in other tilapia populations or species is not clear. In this study, we successfully investigated the QTLs associated with salt tolerance in a mass cross population from the GIFT line of Nile tilapia (Oreochromis niloticus) using a ddRAD-seq-based genome-wide association study (GWAS) and in a full-sib family from the Malaysia red tilapia strain (Oreochromis spp) using QTL-seq. Our study confirmed the major QTL interval that is located at nearly 23.0 Mb of chrLG18 in Nile tilapia and revealed a long QTL cluster across chrLG18 controlling for the salt-tolerant trait in both red tilapia and Nile tilapia. This is the first GWAS analysis on salt tolerance in tilapia. Our finding provides important insights into the genetic architecture of salinity tolerance in tilapia and supplies a basis for fine mapping QTLs, marker-assisted selection, and further detailed functional analysis of the underlying genes for salt tolerance in tilapia.


Asunto(s)
Cíclidos/genética , Tolerancia a la Sal/genética , Animales , Mapeo Cromosómico , Cíclidos/fisiología , Femenino , Estudio de Asociación del Genoma Completo , Masculino , Repeticiones de Microsatélite , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Tolerancia a la Sal/fisiología
7.
Zool Res ; 40(2): 108-112, 2019 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-30213922

RESUMEN

Genetically improved farmed tilapia (GIFT) and GIFT-derived strains account for the majority of farmed tilapia worldwide. As male tilapias grow much faster than females, they are often considered more desirable in the aquacultural industry. Sex reversal of females to males using the male sex hormone 17-α-methyltestosterone (MT) is generally used to induce phenotypic males during large-scale production of all male fingerlings. However, the widespread use of large quantities of sex reversal hormone in hatcheries may pose a health risk to workers and ecological threats to surrounding environments. Breeding procedures to produce genetically all-male tilapia with limited or no use of sex hormones are therefore urgently needed. In this study, by applying marker-assisted selection (MAS) for the selection of YY supermales from a GIFT-derived strain, we identified 24 XY pseudofemale and 431 YY supermale tilapias. Further performance evaluation on the progenies of the YY supermales resulted in male rates of 94.1%, 99.5% and 99.6%, respectively, in three populations, and a daily increase in body weight of 1.4 g at 3 months (n=997). Our study established a highly effective MAS procedure in the selection of YY supermales from a GIFT-derived strain. Furthermore, the development of MAS-selected YY supermales will help reduce the utilization of hormones for controlling sex in the tilapia aquaculture.


Asunto(s)
Selección Genética , Tilapia/genética , Tilapia/fisiología , Cromosoma Y , Animales , Acuicultura , Masculino , Procesos de Determinación del Sexo/genética , Razón de Masculinidad , Tilapia/crecimiento & desarrollo
8.
Mar Biotechnol (NY) ; 20(1): 98-107, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29318417

RESUMEN

Selection of new lines with high salinity tolerance allows for economically feasible production of tilapias in brackish water areas. Mapping QTLs and identifying the markers linked to salinity-tolerant traits are the first steps in the improvement of the tolerance in tilapia through marker-assisted selection techniques. By using QTL-seq strategy and linkage-based analysis, two significant QTL intervals (chrLG4 and chrLG18) on salinity-tolerant traits were firstly identified in the Nile tilapia. Fine mapping with microsatellite and SNP markers suggested a major QTL region that located at 23.0 Mb of chrLG18 and explained 79% of phenotypic variation with a LOD value of 95. Expression analysis indicated that at least 10 genes (e.g., LACTB2, KINH, NCOA2, DIP2C, LARP4B, PEX5R, and KCNJ9) near or within the QTL interval were significantly differentially expressed in intestines, brains, or gills under 10, 15, or 20 ppt challenges. Our findings suggest that QTL-seq can be effectively utilized in QTL mapping of salinity-tolerant traits in fish. The identified major QTL is a promising locus to improve our knowledge on the genetic mechanism of salinity tolerance in tilapia.


Asunto(s)
Cíclidos/genética , Sitios de Carácter Cuantitativo , Tolerancia a la Sal/genética , Animales , Cíclidos/fisiología , Femenino , Ligamiento Genético , Estudio de Asociación del Genoma Completo , Masculino , Repeticiones de Microsatélite , Polimorfismo de Nucleótido Simple , Salinidad , Tolerancia a la Sal/fisiología , Transcriptoma
9.
Gene ; 639: 52-61, 2018 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-28986317

RESUMEN

Hypoxia is one of the critical environmental stressors for fish in aquatic environments. Although accumulating evidences indicate that gene expression is regulated by hypoxia stress in fish, how genes undergoing differential gene expression and/or alternative splicing (AS) in response to hypoxia stress in heart are not well understood. Using RNA-seq, we surveyed and detected 289 differential expressed genes (DEG) and 103 genes that undergo differential usage of exons and splice junctions events (DUES) in heart of a hypoxia tolerant fish, Nile tilapia, Oreochromis niloticus following 12h hypoxic treatment. The spatio-temporal expression analysis validated the significant association of differential exon usages in two randomly selected DUES genes (fam162a and ndrg2) in 5 tissues (heart, liver, brain, gill and spleen) sampled at three time points (6h, 12h, and 24h) under acute hypoxia treatment. Functional analysis significantly associated the differential expressed genes with the categories related to energy conservation, protein synthesis and immune response. Different enrichment categories were found between the DEG and DUES dataset. The Isomerase activity, Oxidoreductase activity, Glycolysis and Oxidative stress process were significantly enriched for the DEG gene dataset, but the Structural constituent of ribosome and Structural molecule activity, Ribosomal protein and RNA binding protein were significantly enriched only for the DUES genes. Our comparative transcriptomic analysis reveals abundant stress responsive genes and their differential regulation function in the heart tissues of Nile tilapia under acute hypoxia stress. Our findings will facilitate future investigation on transcriptome complexity and AS regulation during hypoxia stress in fish.


Asunto(s)
Empalme Alternativo , Expresión Génica , Hipoxia/genética , Estrés Fisiológico/genética , Tilapia/genética , Animales , Exones , Secuenciación de Nucleótidos de Alto Rendimiento
10.
Mar Biotechnol (NY) ; 19(5): 441-453, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28698960

RESUMEN

Exposure to hypoxia induces both acute and chronic stress responses, which plays an important role in health of cultured organisms including growth, reproduction, immunity, and other energy demanding activities. Application of advanced genomic technologies allows rapid identification of hypoxia trait-associated genes and precise selection of superior brood stocks with high tolerance in tilapia. By applying QTL-seq and double-digest restriction-site associated DNA sequencing (ddRAD-seq) techniques, we identified four genome-wide significant quantitative trait loci (QTLs) for hypoxia tolerance and many suggestive QTLs in Nile tilapia. These QTLs explained 6.6-14.7% of the phenotypic variance. Further analysis revealed that single nucleotide polymorphisms (SNPs) in exons of both GPR132 and ABCG4 genes located in genome-wide QTL intervals were significantly associated with hypoxia-tolerant traits. Expression analysis of both genes suggested that they were strong candidate genes involved into hypoxia tolerance in tilapia. Our findings suggest that both QTL-seq and ddRAD-seq techniques can be effectively utilized in QTL mapping of hypoxia traits in fish. Our data supply a basis for further marker-assisted selection of super lines with a high level of tolerance against low oxygen stress in the tilapia.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G/genética , Proteínas de Ciclo Celular/genética , Cíclidos/genética , Proteínas de Peces/genética , Hipoxia/genética , Sitios de Carácter Cuantitativo , Receptores Acoplados a Proteínas G/genética , Animales , Femenino , Expresión Génica , Genoma , Hipoxia/fisiopatología , Masculino , Mutación , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN , Estrés Fisiológico
11.
PLoS One ; 12(3): e0173478, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28278251

RESUMEN

Hypoxia is a major cause of fish morbidity and mortality in the aquatic environment. Hypoxia-inducible factors are very important modulators in the transcriptional response to hypoxic stress. In this study, we characterized and conducted functional analysis of hypoxia-inducible factor HIF1α and its inhibitor HIF1αn in Nile tilapia (Oreochromis niloticus). By cloning and Sanger sequencing, we obtained the full length cDNA sequences for HIF1α (2686bp) and HIF1αn (1308bp), respectively. The CDS of HIF1α includes 15 exons encoding 768 amino acid residues and the CDS of HIF1αn contains 8 exons encoding 354 amino acid residues. The complete CDS sequences of HIF1α and HIF1αn cloned from tilapia shared very high homology with known genes from other fishes. HIF1α show differentiated expression in different tissues (brain, heart, gill, spleen, liver) and at different hypoxia exposure times (6h, 12h, 24h). HIF1αn expression level under hypoxia is generally increased (6h, 12h, 24h) and shows extremely highly upregulation in brain tissue under hypoxia. A functional determination site analysis in the protein sequences between fish and land animals identified 21 amino acid sites in HIF1α and 2 sites in HIF1αn as significantly associated sites (α = 0.05). Phylogenetic tree-based positive selection analysis suggested 22 sites in HIF1α as positively selected sites with a p-value of at least 95% for fish lineages compared to the land animals. Our study could be important for clarifying the mechanism of fish adaptation to aquatic hypoxia environment.


Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Oxigenasas de Función Mixta/genética , Oxigenasas de Función Mixta/metabolismo , Tilapia/genética , Tilapia/metabolismo , Adaptación Fisiológica , Secuencia de Aminoácidos , Animales , Clonación Molecular , Regulación Enzimológica de la Expresión Génica , Hipoxia/genética , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/química , Oxigenasas de Función Mixta/química , Filogenia , Análisis de Secuencia , Tilapia/fisiología
12.
Bioorg Med Chem Lett ; 26(2): 534-539, 2016 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-26639762

RESUMEN

The treatment of epidermal growth factor receptor (EGFR)-driven non-small cell lung cancers with the T790M resistance mutation remains a significant unmet medical need. We report the identification of 4-aminoindazolyl-dihydrofuro[3,4-d]pyrimidines as non-covalent inhibitors of EGFR, with excellent activity against the T790M resistance double mutants and initial single activating mutants. Using an optimization strategy focused on structure-based design and improving PK properties through metabolite identification, we obtained advanced leads with high oral exposure.


Asunto(s)
Receptores ErbB/antagonistas & inhibidores , Furanos/farmacología , Indazoles/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacología , Acrilamidas/farmacología , Compuestos de Anilina/farmacología , Animales , Sitios de Unión , Cristalografía por Rayos X , Perros , Receptores ErbB/química , Clorhidrato de Erlotinib/farmacología , Furanos/síntesis química , Furanos/química , Furanos/farmacocinética , Hepatocitos/metabolismo , Ensayos Analíticos de Alto Rendimiento , Humanos , Enlace de Hidrógeno , Indazoles/síntesis química , Indazoles/química , Indazoles/farmacocinética , Ratones , Microsomas Hepáticos/metabolismo , Mutación Puntual , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacocinética , Pirimidinas/síntesis química , Pirimidinas/química , Pirimidinas/farmacocinética , Ratas
13.
Bioorg Med Chem Lett ; 25(2): 372-7, 2015 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-25435151

RESUMEN

A series of biaryl pyrazole and imidazole Liver X Receptor (LXR) partial agonists has been synthesized displaying LXRß selectivity. The LXRß selective partial agonist 18 was identified with potent induction of ATP binding transporters ABCA1 and ABCG1 in human whole blood (EC50=1.2µM, 55% efficacy). In mice 18 displayed peripheral induction of ABCA1 at 3 and 10mpk doses with no significant elevation of plasma or hepatic triglycerides at these doses, showing an improved profile compared to a full pan-agonist.


Asunto(s)
Transportador 1 de Casete de Unión a ATP/sangre , Imidazoles/farmacología , Hígado/efectos de los fármacos , Receptores Nucleares Huérfanos/agonistas , Pirazoles/farmacología , Sulfonas/farmacología , Animales , Agonismo Parcial de Drogas , Humanos , Imidazoles/química , Imidazoles/farmacocinética , Hígado/metabolismo , Receptores X del Hígado , Ratones , Modelos Moleculares , Estructura Molecular , Plasma/química , Pirazoles/química , Pirazoles/farmacocinética , Relación Estructura-Actividad , Sulfonas/química , Sulfonas/farmacocinética , Distribución Tisular , Triglicéridos/metabolismo
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 31(1): 60-4, 2009 Feb.
Artículo en Chino | MEDLINE | ID: mdl-19317062

RESUMEN

OBJECTIVE: To explore the feasibility of using transpedicular balloon kyphoplasty for aged osteoporotic thoracolumbar burst fractures with an in vitro model. METHODS: Simulated osteoporotic thoracolumbar burst fractures were created in 11 vertebral bodies. The burst fractures without obvious canal occupation were confirmed by spiral CT before the procedure. This operation involved the percutaneous insertion of two inflatable bone tamps into a fractured vertebral body transpedicularly under fluoroscopic guidance. Inflation of the bone tamp elevated the endplates, restored the vertebral body height, while created a cavity to be filled with bone cement. Preoperative and postoperative heights were measured, preoperative and postoperative sagittal diameter of vertebral canals were measured, and the repaired vertebral bodies were compressed to determine strength and stiffness values. The cement distribution and extravasation was evaluated by spiral CT after the procedure. RESULTS: The transpedicular balloon kyphoplasty resulted in the significant restoration of the vertebral body height. The mean vertebral body heights was (20.73 +/- 1.37) mm before operation and (24.82 +/- 1.61) mm after operation (P < 0.01). Preoperative and postoperative sagittal diameter of vertebral canals were similar (P > 0.05). The cement distribution was regular, and the extravasation into spinal cannula was found in one case. The preoperative strength was significantly larger than the postoperative strength, whereas the postoperative stiffness was significantly less than the preoperative stiffness (P < 0.05). CONCLUSIONS: Transpedicular balloon kyphoplasty is an effective way to treat aged osteoporotic thoracolumbar burst fractures without obvious canal occupations and neurologic deficit in vitro. The procedure can increase strength and restore height of aged osteoporotic thoracolumbar burst fractures. Cement distribution and vertebral canal stenosis can be avoided.


Asunto(s)
Cifoplastia/métodos , Cifosis/cirugía , Osteoporosis/complicaciones , Vértebras Torácicas/patología , Cadáver , Humanos , Cifoplastia/instrumentación , Cifosis/diagnóstico por imagen , Cifosis/etiología , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/cirugía , Fusión Vertebral/métodos , Vértebras Torácicas/cirugía , Tomografía Computarizada por Rayos X
15.
J Med Chem ; 52(4): 904-7, 2009 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-19159286

RESUMEN

Azepino[4,5-b]indoles have been identified as potent agonists of the farnesoid X receptor (FXR). In vitro and in vivo optimization has led to the discovery of 6m (XL335, WAY-362450) as a potent, selective, and orally bioavailable FXR agonist (EC(50) = 4 nM, Eff = 149%). Oral administration of 6m to LDLR(-/-) mice results in lowering of cholesterol and triglycerides. Chronic administration in an atherosclerosis model results in significant reduction in aortic arch lesions.


Asunto(s)
Aterosclerosis/tratamiento farmacológico , Azepinas/farmacología , Proteínas de Unión al ADN/agonistas , Indoles/farmacología , Receptores Citoplasmáticos y Nucleares/agonistas , Factores de Transcripción/agonistas , Administración Oral , Animales , Aorta Torácica/patología , Aterosclerosis/prevención & control , Azepinas/farmacocinética , Azepinas/uso terapéutico , Colesterol/sangre , Modelos Animales de Enfermedad , Descubrimiento de Drogas , Indoles/farmacocinética , Indoles/uso terapéutico , Ratones , Ratones Noqueados , Receptores de LDL/deficiencia , Triglicéridos/sangre
16.
Zhongguo Gu Shang ; 22(11): 835-7, 2009 Nov.
Artículo en Chino | MEDLINE | ID: mdl-20084941

RESUMEN

OBJECTIVE: To investigate the "window" surgical exposure strategy of the upper anterior cervical retropharyngeal approach for the exposure and decompression and instrumentation of the upper cervical spine. METHODS: From Jan. 2000 to July 2008, 5 patients with upper cervical spinal injuries were treated by surgical operation included 4 males and 1 female with and average age of 35 years old ranging from 16 to 68 years. There were 2 cases of Hangman's fractures (type II ), 2 of C2.3 intervertebral disc displacement and 1 of C2 vertebral body tuberculosis. All patients underwent the upper cervical anterior retropharyngeal approach through the "window" between the hypoglossal nerve and the superior laryngeal nerve and pharynx and carotid artery. Two patients of Hangman's fractures underwent the C2,3 intervertebral disc discectomy, bone graft fusion and internal fixation. Two patients of C2,3 intervertebral disc displacement underwent the C2,3 intervertebral disc discectomy, decompression bone graft fusion and internal fixation. One patient of C2 vertebral body tuberculosis was dissected and resected and the focus and the cavity was filled by bone autografting. RESULTS: C1 anterior arch to C3 anterior vertebral body were successful exposed. Lesion resection or decompression and fusion were successful in all patients. All patients were followed-up for from 5 to 26 months (means 13.5 months). There was no important vascular and nerve injury and no wound infection. Neutral symptoms was improved and all patient got successful fusion. CONCLUSION: The "window" surgical exposure surgical technique of the upper cervical anterior retropharyngeal approach is a favorable strategy. This approach strategy can be performed with full exposure for C1-C3 anterior anatomical structure, and can get minimally invasive surgery results and few and far between wound complication, that is safe if corresponding experience is achieved.


Asunto(s)
Vértebras Cervicales/cirugía , Faringe , Adolescente , Adulto , Anciano , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/lesiones , Femenino , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/fisiopatología , Fracturas Óseas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Fusión Vertebral , Tomografía Computarizada por Rayos X , Adulto Joven
17.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 27(2): 174-8, 2005 Apr.
Artículo en Chino | MEDLINE | ID: mdl-15960261

RESUMEN

OBJECTIVE: To investigate the selectivity and individualization of transpedicular balloon kyphoplasty for aged osteoporotic spinal fracture. METHODS: Twenty-two consecutive procedures were performed in 17 aged patients with osteoporotic spinal compression fractures from April 2002 to June 2004. The signal changes in different sequences were confirmed by magnetic resonance imaging before the procedures. This operation involved the percutaneous insertion of two inflatable bone tamps into a fractured vertebral body transpedicularly under fluoroscopic guidance. Every patient was treated individually, according to the results of radiography and CT scan before operation. Preoperative and postoperative complications, visual analogue scale, and radiographic findings such as vertebral height and Cobb angle were recorded and analyzed. RESULTS: All patients tolerated the procedure well with immediate relief of their back pain in 24 hours. There was no leakage of cement into the epidura. The mean loss percent of the anterior and middle vertebral heights were (35.32 +/- 13.15)% and (27.53 +/- 12.61)% before operation, and (14.21 +/- 12.43)% and (16.2 +/- 7.5)% after operation. The height restoration of vertebra was confirmed by X-ray after the procedure (P < 0.01). The mean kyphosis was improved from (25.3 +/- 4.2) degrees to (8.6 +/- 5.1) degrees. No complications occurred. No patient had nerve injury. The patients were allowed to walk next day after the procedure. CONCLUSION: The selectivity and individualization of transpedicular balloon kyphoplasty for aged osteoporotic spinal fractures has satisfactory short-term clinical efficacy. It is also an effective way to prevent complications.


Asunto(s)
Fijación Interna de Fracturas/métodos , Cifosis/cirugía , Osteoporosis Posmenopáusica/complicaciones , Osteoporosis/complicaciones , Fracturas de la Columna Vertebral/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Fracturas Espontáneas/etiología , Fracturas Espontáneas/cirugía , Humanos , Cifosis/etiología , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos
18.
Org Biomol Chem ; 2(3): 330-6, 2004 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-14747861

RESUMEN

In an attempt to obtain the para-f isomer, rac-(1R,4aR,9aR)-2-methyl-1,3,4,9a-tetrahydro-2H-1,4a-propanobenzofuro[2,3-c]pyridin-6-ol, via mesylation of an intermediate 9[small alpha]-hydroxyphenylmorphan, we obtained, instead, a rearranged chloro compound with a 5-membered nitrogen ring, 7-chloro-3a-(2,5-dimethoxyphenyl)-1-methyl-octahydroindole. This indole underwent a second rearrangement to give us the desired para-f isomer. The structures of the intermediate indole and the final product were unequivocally established by X-ray crystallography. A resynthesis of the known rac-(1R,4aR,9aR)-2-methyl-1,3,4,9a-tetrahydro-2H-1,4a-propanobenzofuro[2,3-c]pyridin-8-ol, the ortho-f isomer, was achieved using the reaction conditions for the para-f isomer, as well as under Mitsunobu reaction conditions where, unusually, the oxide-bridge ring in the 5-phenylmorphan was closed to obtain the desired product. The synthesis of the para-f isomer adds an additional compound to those oxide-bridged phenylmorphans that were initially visualized and synthesized; the establishment of the structure and configuration of 8 of the theoretically possible 12 racemates has now been achieved. The X-ray crystallographic structure analysis of the para-f isomer provides essential data that will be needed to establish the configuration of a ligand necessary to interact with an opioid receptor.


Asunto(s)
Benzofuranos/química , Benzofuranos/síntesis química , Morfinanos/química , Morfinanos/síntesis química , Óxidos/química , Piridinas/química , Piridinas/síntesis química , Cristalografía por Rayos X , Isomerismo , Conformación Molecular , Estructura Molecular
19.
Nucl Med Biol ; 31(1): 125-31, 2004 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-14741577

RESUMEN

A synthetic procedure for the preparation of [18F]FPCBT, an imaging agent for the dopamine transporter (DAT), has been developed. The radiosynthesis was carried out in a two step procedure. Even though the yield was low, we were able to prepare 20 to 30 mCi of the product, which was enough for two or three studies. The radiochemical purity was greater than 96%. The in vivo properties of this radiotracer were evaluated using baboon and it showed highest uptake in the striatum. The studies also revealed that the maximum uptake was reached within 7 to 10 minutes post injection. Plasma metabolite analysis indicated that there is only one metabolite and it is less lipophilic than the parent compound. [18F]FPCBT displayed good brain uptake and its high target to non target ratio indicate that it is a potential candidate for DAT imaging.


Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Nortropanos/farmacocinética , Animales , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Femenino , Marcaje Isotópico/métodos , Tasa de Depuración Metabólica , Nortropanos/sangre , Nortropanos/química , Papio , Radiofármacos/sangre , Radiofármacos/síntesis química , Radiofármacos/farmacocinética , Distribución Tisular , Tomografía Computarizada de Emisión/métodos
20.
Zhonghua Wai Ke Za Zhi ; 42(21): 1299-302, 2004 Nov 07.
Artículo en Chino | MEDLINE | ID: mdl-15634429

RESUMEN

OBJECTIVE: To contrast single and double balloon-inflated kyphoplasty for vertebral compression fractures (VCFs) and evaluate its clinical efficacy. METHODS: From May 2000 to May 2004, 90 consecutive procedures were performed in 58 patients who suffered from painful vertebral compression fractures, transferring tumour and angioma. Ninety vertebrae were inflated while 62 as A group were double balloon and 28 as B group were single balloon, fracture reduction and bone cement augmentation. Preoperative and postoperative symptom levels, variables, complications were recorded and the vertebral height and Cobb angle were measured and analyzed. RESULTS: All patients' pain was alleviated or disappeared without syndrome, and the vertebral height and Cobb angle of both groups were improved. The average recovery rate was 72.6% (22.9% approximately 100%), Cobb angle from 17.9 degrees (3.1 degrees approximately 31.6 degrees ) were corrected to 9.6 degrees (0.6 degrees approximately 28.2 degrees ), the average angle was 8.7 degrees (0.3 degrees approximately 27.2 degrees ), and the contrast between preoperative and postoperative showed obvious differences (P <0.001). The average recovery rate of A group was 77.6% (55.3% approximately 100%), B group was 64.3% (22.9% approximately 100%). The average postoperative Cobb angle of A group was 9.9 degrees (0.3 degrees approximately 27.2 degrees ), B group was 8.6 degrees (0.6 degrees approximately 19.8 degrees ) (P >0.05). CONCLUSIONS: As a promising minimally invasive surgery, balloon kyphoplasty can provide early relief of pain and improve the function as well as spinal alignment in treatment of painful compression fracture owing to recovering the vertebral height and Cobb angle of the vertebral body. Single balloon-inflated kyphoplasty can improve VCFs as double balloon.


Asunto(s)
Fracturas por Compresión/cirugía , Cifosis/cirugía , Procedimientos Ortopédicos/métodos , Fracturas de la Columna Vertebral/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Cementos para Huesos/uso terapéutico , Femenino , Fracturas por Compresión/complicaciones , Humanos , Cifosis/etiología , Vértebras Lumbares/lesiones , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Procedimientos Ortopédicos/instrumentación , Estudios Retrospectivos , Fracturas de la Columna Vertebral/complicaciones , Vértebras Torácicas/lesiones , Vértebras Torácicas/cirugía
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...