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1.
J Neurosurg ; 134(3): 1054-1063, 2020 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-32384279

RESUMEN

OBJECTIVE: The anterior thalamic nucleus (ATN) is a common target for deep brain stimulation (DBS) for the treatment of drug-refractory epilepsy. However, no atlas-based optimal DBS (active contacts) target within the ATN has been definitively identified. The object of this retrospective study was to analyze the relationship between the active contact location and seizure reduction to establish an atlas-based optimal target for ATN DBS. METHODS: From among 25 patients who had undergone ATN DBS surgery for drug-resistant epilepsy between 2016 and 2018, those who had follow-up evaluations for more than 1 year were eligible for study inclusion. After an initial stimulation period of 6 months, patients were classified as responsive (≥ 50% median decrease in seizure frequency) or nonresponsive (< 50% median decrease in seizure frequency) to treatment. Stimulation parameters and/or active contact positions were adjusted in nonresponsive patients, and their responsiveness was monitored for at least 1 year. Postoperative CT scans were coregistered nonlinearly with preoperative MR images to determine the center coordinate and atlas-based anatomical localizations of all active contacts in the Montreal Neurological Institute (MNI) 152 space. RESULTS: Nineteen patients with drug-resistant epilepsy were followed up for at least a year following bilateral DBS electrode implantation targeting the ATN. Active contacts located more adjacent to the center of gravity of the anterior half of the ATN volume, defined as the anterior center (AC), were associated with greater seizure reduction than those not in this location. Intriguingly, the initially nonresponsive patients could end up with much improved seizure reduction by adjusting the active contacts closer to the AC at the final postoperative follow-up. CONCLUSIONS: Patients with stimulation targeting the AC may have a favorable seizure reduction. Moreover, the authors were able to obtain additional good outcomes after electrode repositioning in the initially nonresponsive patients. Purposeful and strategic trajectory planning to target this optimal region may predict favorable outcomes of ATN DBS.


Asunto(s)
Estimulación Encefálica Profunda/métodos , Epilepsia Refractaria/terapia , Tálamo/patología , Adulto , Núcleos Talámicos Anteriores/cirugía , Atlas como Asunto , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/patología , Electrodos Implantados , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tálamo/diagnóstico por imagen , Tálamo/cirugía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
2.
Mindfulness (N Y) ; 9(6): 1857-1866, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30524515

RESUMEN

The majority of meditation involves focusing attention on internal events or sensations and becoming aware of emotions. The insula cortex, through a functional connection with the prefrontal cortex and other brain regions, plays a key role in integrating external sensory information with internal bodily state signals and emotional awareness. The purpose of this exploratory study was to examine the resting-state functional connectivity of the insula with other brain regions in meditation practitioners and control subjects. Thirty-five Brain Wave Vibration meditation practitioners and 33 controls without meditation experience were included in this study. All subjects underwent 4.68-min resting-state functional scanning runs using magnetic resonance imaging. The anterior and posterior insulae were chosen as seed regions for the functional connectivity map. Meditation practitioners showed significantly greater insula-related functional connectivity in the thalamus, caudate, middle frontal gyrus, and superior temporal gyrus than did controls. Control subjects demonstrated greater functional connectivity with the posterior insula in the parahippocampal gyrus. Our findings suggest that the practice of Brain Wave Vibration meditation may be associated with functional differences in regions related to focused attention, executive control, and emotional awareness and regulation.

3.
World J Gastroenterol ; 23(1): 173-177, 2017 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-28104993

RESUMEN

Multiple primary malignancy is defined as two or more malignancies detected in an individual person. In particular, synchronous quintuple primary malignancy is extremely rare. A 52-year-old male with anal pain and intermittent blood-tinged stool was diagnosed with malignancies in the stomach, jejunum, ascending colon, transverse colon and rectum. He underwent a subtotal gastrectomy, segmental resection of the jejunum and total protocolectomy with end ileostomy. The postoperative pathologic findings were moderate differentiated gastric adenocarcinoma (pT1bN0M0, pStageIA), combined adenocarcinoma and neuroendocrine carcinoma of the jejunum (pT3N0M0, pStageIIA), three mucinous adenocarcinoma of the ascending colon (pT3N0M0, pStageIIA), transverse colon (pT1N0M0, pStageI) and rectum (pT3N1aM0, pStageIIIB). The tumors did not lack MLH-1 and MSH-2 expression, as the markers (bat26, D5S346, bat25, D2S123) suggest MSI-H presence. Adjuvant chemoradiotherapy was started according to regimen, FOLFOX 4 for advanced rectal cancer. Six years post-operation, the patient is currently attending regular follow-ups without recurrence or metastasis.


Asunto(s)
Adenocarcinoma Mucinoso/diagnóstico , Neoplasias del Colon/diagnóstico , Neoplasias del Yeyuno/diagnóstico , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias del Recto/diagnóstico , Neoplasias Gástricas/diagnóstico , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Dolor en Cáncer/etiología , Quimioradioterapia Adyuvante , Colectomía , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Neoplasias del Colon/terapia , Endoscopía Gastrointestinal , Fluorouracilo/uso terapéutico , Gastrectomía/métodos , Hemorragia Gastrointestinal/etiología , Humanos , Ileostomía , Neoplasias del Yeyuno/genética , Neoplasias del Yeyuno/patología , Neoplasias del Yeyuno/terapia , Leucovorina/uso terapéutico , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Primarias Múltiples/genética , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/terapia , Compuestos Organoplatinos/uso terapéutico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias del Recto/genética , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia , Tomografía Computarizada por Rayos X
4.
Mol Pharm ; 13(5): 1528-39, 2016 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-26998616

RESUMEN

Monitoring of drug release from a heat-activated liposome carrier provides an opportunity for real-time control of drug delivery and allows prediction of the therapeutic effect. We have developed short-chain elastin-like polypeptide-incorporating thermosensitive liposomes (STLs). Here, we report the development of STL encapsulating gadobenate dimeglumine (Gd-BOPTA), a MRI contrast agent, and doxorubicin (Dox) (Gd-Dox-STL). The Dox release profile from Gd-Dox-STL was comparable to Gd-Dox-LTSL; however, the serum stability of Gd-Dox-STL was much higher than Gd-Dox-LTSL. MRI studies showed that the difference in T1 relaxation time between 37 and 42 °C for Gd-Dox-STL was larger than the difference for Gd-Dox-LTSL. Although relaxivity for both liposomes at 42 °C was similar, the relaxivity of Gd-Dox-STL at 37 °C was 2.5-fold lower than that of Gd-Dox-LTSL. This was likely due to Gd-BOPTA leakage from the LTSL because of low stability at 37 °C. Pharmacokinetic studies showed plasma half-lives of 4.85 and 1.95 h for Gd-Dox-STL and Gd-Dox-LTSL, respectively, consistent with in vitro stability data. In vivo MRI experiments demonstrated corelease of Dox and Gd-BOPTA from STL under mild hyperthermia induced by high-intensity focused ultrasound (HIFU), which suggests STL is a promising tumor selective formulation when coupled with MR-guided HIFU.


Asunto(s)
Antineoplásicos/administración & dosificación , Liposomas/administración & dosificación , Animales , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Medios de Contraste/administración & dosificación , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacocinética , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos/fisiología , Elastina/administración & dosificación , Semivida , Calor , Hipertermia Inducida/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Meglumina/administración & dosificación , Meglumina/análogos & derivados , Meglumina/farmacocinética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Compuestos Organometálicos/administración & dosificación , Compuestos Organometálicos/farmacocinética , Péptidos/administración & dosificación , Temperatura , Ultrasonografía/métodos
5.
J Sleep Res ; 25(2): 181-9, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26610427

RESUMEN

Functional imaging studies and voxel-based morphometry analysis of brain magnetic resonance imaging showed abnormalities in the hypothalamus-thalamus-orbitofrontal pathway, demonstrating altered hypocretin pathway in narcolepsy. Those distinct morphometric changes account for problems in wake-sleep control, attention and memory. It also raised the necessity to evaluate white matter changes. To investigate brain white matter alterations in drug-naïve narcolepsy patients with cataplexy and to explore relationships between white matter changes and patient clinical characteristics, drug-naïve narcolepsy patients with cataplexy (n = 22) and healthy age- and gender-matched controls (n = 26) were studied. Fractional anisotropy and mean diffusivity images were obtained from whole-brain diffusion tensor imaging, and tract-based spatial statistics were used to localize white matter abnormalities. Compared with controls, patients showed significant decreases in fractional anisotropy of white matter of the bilateral anterior cingulate, fronto-orbital area, frontal lobe, anterior limb of the internal capsule and corpus callosum, as well as the left anterior and medial thalamus. Patients and controls showed no differences in mean diffusivity. Among patients, mean diffusivity values of white matter in the bilateral superior frontal gyri, bilateral fronto-orbital gyri and right superior parietal gyrus were positively correlated with depressive mood. This tract-based spatial statistics study demonstrated that drug-naïve patients with narcolepsy had reduced fractional anisotropy of white matter in multiple brain areas and significant relationship between increased mean diffusivity of white matter in frontal/cingulate and depression. It suggests the widespread disruption of white matter integrity and prevalent brain degeneration of frontal lobes according to a depressive symptom in narcolepsy.


Asunto(s)
Cataplejía/patología , Sustancia Blanca/patología , Adolescente , Adulto , Anisotropía , Cataplejía/complicaciones , Cataplejía/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Niño , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/patología , Depresión/complicaciones , Depresión/patología , Imagen de Difusión Tensora , Femenino , Humanos , Hipotálamo/diagnóstico por imagen , Hipotálamo/patología , Imagen por Resonancia Magnética , Masculino , Sustancia Blanca/diagnóstico por imagen , Adulto Joven
6.
J Nanosci Nanotechnol ; 15(8): 5656-9, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26369133

RESUMEN

We examined the formulation of liquid crystalline systems (LCS) including 5% TSE extracts and analyzed marker substances of the 5% TSE ointment by HPLC-DAD. The TSE extracts were evaluated for its anti-bacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. We found the extracts showed predominant activity against selected bacterial species. The result of the polarized light microscopy, differential scanning calorimetry (DSC), small-angle X-ray diffraction (SXRD), and rheology analysis indicated the presence of LCS structures with lamellar arrangement. DSC of the TSE formulas showed higher transition peak temperature at 60 °c for the phase. SXRD observation of the LCS formulas showed that the structures of the LCS formulas were in the lamellar liquid crystalline phase. Further, to ensure the quality and purity of the TSE ointment, HPLC analysis was performed by measuring the. content of 2 marker substances. The contents of marker substances in the TSE ointment were calculated as 0.078% (paeoniflorin) and 0.031% (glycyrrhizin), respectively. Taken altogether, our study report successful generation of LCS made of 5% TSE ointment and its antimicrobial activity. Moreover, the quantitation of the two active components enable a proper quality control of the TSE extracts, that is essential for the development of ointment products.


Asunto(s)
Fenómenos Fisiológicos Bacterianos/efectos de los fármacos , Preparaciones de Acción Retardada/química , Cristales Líquidos/química , Pomadas/administración & dosificación , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Antibacterianos/administración & dosificación , Antibacterianos/síntesis química , Supervivencia Celular/efectos de los fármacos , Preparaciones de Acción Retardada/administración & dosificación , Combinación de Medicamentos , Composición de Medicamentos/métodos , Diseño de Fármacos , Pomadas/síntesis química , Plantas Medicinales/química
7.
Exp Biol Med (Maywood) ; 240(4): 477-87, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25258426

RESUMEN

Since Korean mistletoe (Viscum album) has been used for alleviating metabolic diseases, it may also prevent the impairment of energy, glucose, lipid, and bone metabolisms in an estrogen-deficient animal model. We determined that long-term consumption of Korean mistletoe water extract (KME) can alleviate menopausal symptoms such as hot flush, increased abdominal fat mass, dyslipidemia, hyperglycemia, and decreased bone mineral density in ovariectomized (OVX) rats fed a high-fat diet, and explored the mechanisms of the effects. OVX rats were divided into four groups and fed high-fat diets supplemented with either 0.6% dextrin (control), 0.2% lyophilized KME + 0.4% dextrin (KME-L), or 0.6% lyophilized KME (KME-H). Sham rats were fed with the high-fat diets with 0.6% dextrin as a normal-control without estrogen deficiency. After eight weeks, OVX rats exhibited impaired energy, glucose and lipid metabolism, and decreased uterine and bone masses. KME-L did not alleviate energy dysfunction. However, KME-H lowered serum levels of total-, LDL-cholesterol, and triglycerides and elevated serum HDL-cholesterol levels in OVX rats with dyslipidemia, to similar levels as normal-control rats. Furthermore, KME-H improved HOMA-IR, an indicator of insulin resistance, in OVX rats. Surprisingly, KME-H fed rats had greater lean mass in the abdomen and leg without differences in fat mass but neither dosage of KME altered bone mineral density in the lumbar spine and femur. The increased lean mass was related to greater phosphorylation of mTOR and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) in the quadriceps muscles. Hepatic triglyceride contents were lowered with KME-H in OVX rats by increasing carnitine palmitoyltransferase-1 (CPT-1) expression and decreasing fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP-1c) expression. In conclusion, KME may be useful for preventing some menopausal symptoms such as hot flushes, dyslipidemia, hepatic steatosis, and loss of muscle mass in post-menopausal women.


Asunto(s)
Dislipidemias/prevención & control , Hígado Graso/prevención & control , Sofocos/prevención & control , Atrofia Muscular/prevención & control , Ovariectomía , Extractos Vegetales/uso terapéutico , Viscum album , Animales , Suplementos Dietéticos , Modelos Animales de Enfermedad , Dislipidemias/metabolismo , Estrógenos/deficiencia , Hígado Graso/metabolismo , Femenino , Sofocos/metabolismo , Hiperglucemia/metabolismo , Hiperglucemia/prevención & control , Corea (Geográfico) , Menopausia/metabolismo , Atrofia Muscular/metabolismo , Osteoporosis/metabolismo , Osteoporosis/prevención & control , Extractos Vegetales/administración & dosificación , Ratas , Ratas Sprague-Dawley
8.
J Agric Food Chem ; 62(49): 11876-83, 2014 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-25383453

RESUMEN

The present study investigated the effects of viscothionin, a compound isolated from Korean mistletoe (Viscum album coloratum), on nonalcoholic fatty liver disease (NAFLD) in both in vitro and in vivo models. A connection was discovered between viscothionin and the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which is involved in lipid metabolism. Viscothionin was shown to significantly attenuate lipid accumulation in HepG2 cells treated with oleic acid, which induces lipid accumulation. Moreover, the phosphorylation of AMPK and acetyl-coenzyme A carboxylase in HepG2 cells was increased by viscothionin treatment. Viscothionin was orally administered to high fat diet-induced obese mice and subsequently histopathological analysis associated with AMPK signaling pathways was evaluated. A significant reduction in the extent of hepatic steatosis was revealed in viscothionin-treated obese mice. Thus, viscothionin mediates its beneficial effects on NAFLD via AMPK signaling pathways, suggesting that it may be a potential target for novel NAFLD treatments.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Muérdago/química , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Péptidos/administración & dosificación , Extractos Vegetales/administración & dosificación , Proteínas Quinasas Activadas por AMP/genética , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/metabolismo , Animales , Activadores de Enzimas , Acido Graso Sintasa Tipo I/genética , Acido Graso Sintasa Tipo I/metabolismo , Células Hep G2 , Humanos , Metabolismo de los Lípidos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Enfermedad del Hígado Graso no Alcohólico/enzimología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Fosforilación , República de Corea
9.
Food Chem Toxicol ; 72: 228-33, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25084483

RESUMEN

Rutin is derived from buckwheat, apples, and black tea. It has been shown to have beneficial anti-inflammatory and antioxidant effects. Ethanol is a central nervous system depressant and neurotoxin. Its metabolite, acetaldehyde, is critically toxic. Aldehyde dehydrogenase 2 (ALDH2) metabolizes acetaldehyde into nontoxic acetate. This study examined rutin's effects on ALDH2 activity in hippocampal neuronal cells (HT22 cells). Rutin's protective effects against acetaldehyde-based ethanol neurotoxicity were confirmed. Daidzin, an ALDH2 inhibitor, was used to clarify the mechanisms of rutin's protective effects. Cell viability was significantly increased after rutin treatment. Rutin significantly reversed ethanol-increased Bax, cytochrome c expression and caspase 3 activity, and decreased Bcl-2 and Bcl-xL protein expression in HT22 cells. Interestingly, rutin increased ALDH2 expression, while daidzin reversed this beneficial effect. Thus, this study demonstrates rutin protects HT22 cells against ethanol-induced neurotoxicity by increasing ALDH2 activity.


Asunto(s)
Aldehído Deshidrogenasa/metabolismo , Etanol/toxicidad , Hipocampo/efectos de los fármacos , Extractos Vegetales/farmacología , Rutina/farmacología , Aldehído Deshidrogenasa Mitocondrial , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/genética , Caspasa 3/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citocromos c/genética , Citocromos c/metabolismo , Isoflavonas/farmacología , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neuronas/citología , Neuronas/efectos de los fármacos , Transducción de Señal , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo , Proteína bcl-X/genética , Proteína bcl-X/metabolismo
10.
J Med Food ; 17(7): 742-8, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24971771

RESUMEN

The aim of this study was to clarify the efficacy of procyanidin C1 (Pro C1) for modulating vascular tone. Pro C1 induced a potent vasorelaxant effect on phenylephrine-constricted endothelium-intact thoracic aortic rings, but had no effect on denuded thoracic aortic rings. Moreover, Pro C1 caused a significant increase in nitric oxide (NO) production in endothelial cells. Pro C1-induced vasorelaxation and Pro C1-induced NO production were significantly decreased in the presence of a nonspecific potassium channel blocker (tetraethylammonium chloride [TEA]), an endothelial NO synthase inhibitor (N(G)-monomethyl-L-arginine [L-NMMA]), and a store-operated calcium entry inhibitor (2-aminoethyl diphenylborinate [2-APB]). Pro C1-induced vasorelaxation was also completely abolished by an inhibitor of soluble guanyl cyclase, which suggests that the Pro C1 effects observed involved cyclic guanosine monophosphate (cGMP) production. Interestingly, Pro C1 significantly enhanced basal cGMP levels. Taken together, these results indicate that Pro C1-induced vasorelaxation is associated with the activation of the calcium-dependent NO/cGMP pathway, involving potassium channel activation. Thus, Pro C1 may represent a novel and potentially therapeutically relevant compound for the treatment of cardiovascular diseases.


Asunto(s)
Biflavonoides/farmacología , Catequina/farmacología , GMP Cíclico/metabolismo , Óxido Nítrico/metabolismo , Proantocianidinas/farmacología , Transducción de Señal/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Animales , Aorta Torácica/efectos de los fármacos , Compuestos de Boro/farmacología , Células Cultivadas , Células Endoteliales/efectos de los fármacos , Guanilato Ciclasa/antagonistas & inhibidores , Guanilato Ciclasa/metabolismo , Técnicas In Vitro , Masculino , Óxido Nítrico Sintasa de Tipo III/metabolismo , Bloqueadores de los Canales de Potasio/farmacología , Ratas , Ratas Sprague-Dawley , Tetraetilamonio/farmacología , Vasodilatadores/farmacología , omega-N-Metilarginina/farmacología
11.
Neuroreport ; 25(4): 211-8, 2014 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-24518227

RESUMEN

In this study, we have shown the potential of a voxel-based analysis for imaging amyloid plaques and its utility in monitoring therapeutic response in Alzheimer's disease (AD) mice using manganese oxide nanoparticles conjugated with an antibody of Aß1-40 peptide (HMON-abAß40). T1-weighted MR brain images of a drug-treated AD group (n=7), a nontreated AD group (n=7), and a wild-type group (n=7) were acquired using a 7.0 T MRI system before (D-1), 24-h (D+1) after, and 72-h (D+3) after injection with an HMON-abAß40 contrast agent. For the treatment of AD mice, DAPT was injected intramuscularly into AD transgenic mice (50 mg/kg of body weight). For voxel-based analysis, the skull-stripped mouse brain images were spatially normalized, and these voxels' intensities were corrected to reduce voxel intensity differences across scans in different mice. Statistical analysis showed higher normalized MR signal intensity in the frontal cortex and hippocampus of AD mice over wild-type mice on D+1 and D+3 (P<0.01, uncorrected for multiple comparisons). After the treatment of AD mice, the normalized MR signal intensity in the frontal cortex and hippocampus decreased significantly in comparison with nontreated AD mice on D+1 and D+3 (P<0.01, uncorrected for multiple comparisons). These results were confirmed by histological analysis using a thioflavin staining. This unique strategy allows us to detect brain regions that are subjected to amyloid plaque deposition and has the potential for human applications in monitoring therapeutic response for drug development in AD.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología , Encéfalo/patología , Dipéptidos/uso terapéutico , Imagen por Resonancia Magnética/métodos , Placa Amiloide/patología , Péptidos beta-Amiloides/inmunología , Animales , Anticuerpos , Encéfalo/efectos de los fármacos , Medios de Contraste , Inhibidores Enzimáticos/uso terapéutico , Femenino , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/patología , Hipocampo/efectos de los fármacos , Hipocampo/patología , Procesamiento de Imagen Asistido por Computador , Compuestos de Manganeso , Ratones , Ratones Transgénicos , Nanopartículas , Óxidos , Fragmentos de Péptidos/inmunología , Placa Amiloide/tratamiento farmacológico , Factores de Tiempo
12.
Mol Med Rep ; 8(5): 1425-31, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24064967

RESUMEN

Angiogenesis inhibition is an attractive therapeutic strategy in the management of solid tumors. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) are key factors in growth and neovascularization of hepatocellular carcinoma (HCC). Brivanib is a novel, orally available dual tyrosine kinase inhibitor that selectively targets the key angiogenesis receptors VEGF­R2, FGF­R1 and FGF­R2. Recently, high­resolution magic angle spinning magnetic resonance spectroscopy (HR­MAS MRS) has provided the opportunity to investigate more detailed metabolic profiles from intact tissue specimens that are correlated with histopathology and is thus, a promising tool for monitoring changes induced by treatment. In the present study, 1H HR­MAS MRS and immunohistochemistry were used to investigate the antitumor efficacy of brivanib in HCC xenograft models. Tumor growth was significantly suppressed in brivanib­treated mice compared with the controls and treatment was associated with the inhibition of angiogenesis, increased apoptosis and inhibition of cell proliferation. Furthermore, HR­MAS techniques showed altered metabolic profiles between the two groups. HR­MAS spectra demonstrated a significant decrease in choline metabolite levels in the treated groups, concurrent with decreased cell proliferation and increased apoptosis. The results showed that 1H HR­MAS MRS provides quantitative metabolite information that may be used to analyze the efficacy of brivanib treatment in Hep3B tumor xenografts. Thus, the HR­MAS MRS technique may be a complementary method to support histopathological results and increase its potential for use in the clinic.


Asunto(s)
Alanina/análogos & derivados , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Espectroscopía de Resonancia Magnética/métodos , Triazinas/uso terapéutico , Alanina/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/metabolismo , Proliferación Celular/efectos de los fármacos , Humanos , Técnicas para Inmunoenzimas , Neoplasias Hepáticas/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
13.
J Ethnopharmacol ; 137(3): 1197-206, 2011 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-21821108

RESUMEN

ETHNOPHARMACOLOGICAL SIGNIFICANCE: Phaseolus angularis Wight (adzuki bean) is an ethnopharmacologically well-known folk medicine that is prescribed for infection, edema, and inflammation of the joints, appendix, kidney and bladder in Korea, China and Japan. AIM OF STUDY: The anti-inflammatory effect of this plant and its associated molecular mechanisms will be investigated. MATERIALS AND METHODS: The immunomodulatory activity of Phaseolus angularis ethanol extract (Pa-EE) in toll like receptor (TLR)-activated macrophages induced by ligands such as lipopolysaccharide (LPS), Poly (I:C), and pam3CSK was investigated by assessing nitric oxide (NO) and prostaglandin (PG)E(2) levels. To identify which transcription factors such as nuclear factor (NF)-κB and their signaling enzymes can be targeted to Pa-EE, biochemical approaches including reporter gene assays, immunoprecipitation, kinase assays, and immunoblot analyses were also employed. Finally, whether Pa-EE was orally available, ethanol (EtOH)/hydrochloric acid (HCl)-induced gastritis model in mice was used. RESULTS: Pa-EE dose-dependently suppressed the release of PGE(2) and NO in LPS-, Poly(I:C)-, and pam3CSK-activated macrophages. Pa-EE strongly down-regulated LPS-induced mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Interestingly, Pa-EE markedly inhibited NF-κB, activator protein (AP)-1, and cAMP response element binding protein (CREB) activation; further, according to direct kinase assays and immunoblot analyses, Pa-EE blocked the activation of the upstream signaling molecules spleen tyrosine kinase (Syk), p38, and transforming growth factor ß-activated kinase 1 (TAK1). Finally, orally administered Pa-EE clearly ameliorated EtOH/HCl-induced gastritis in mice. CONCLUSION: Our results suggest that Pa-EE can be further developed as a promising anti-inflammatory remedy because it targets multiple inflammatory signaling enzymes and transcription factors.


Asunto(s)
Antiinflamatorios/farmacología , Etanol/química , Gastritis/prevención & control , Macrófagos/efectos de los fármacos , Phaseolus , Extractos Vegetales/farmacología , Solventes/química , Administración Oral , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Gastritis/inducido químicamente , Gastritis/patología , Células HEK293 , Humanos , Ácido Clorhídrico , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Quinasas Quinasa Quinasa PAM/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , FN-kappa B/genética , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Phaseolus/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Proteínas Tirosina Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Quinasa Syk , Receptores Toll-Like/metabolismo , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo , Transfección , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Familia-src Quinasas/metabolismo
14.
J Ethnopharmacol ; 134(1): 11-7, 2011 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-20832462

RESUMEN

AIM OF THE STUDY: Sanguisorba officinalis, a well known valuable medicinal plant in Korea, China and Japan used traditionally for the treatment of inflammatory and metabolic diseases such as diarrhea, chronic intestinal infections, duodenal ulcers, and bleeding. Recent studies have revealed that its aqueous or ethanolic extracts exhibit a variety of pharmacological activities such as anti-oxidative, anti-cancer, anti-lipid peroxidation, anti-atherogenic, and vasorelaxant effects. Systematic studies on the anti-inflammatory effect of this plant and its molecular mechanisms have not yet been fully investigated. Ethanol extract of Sanguisorba officinalis (So-EE) the lipopolysaccharide (LPS)-stimulated macrophages and production of inflammatory mediators were employed to assess these properties. RESULTS: So-EE significantly suppressed the production of nitric oxide (NO) and prostaglandin (PG) E(2) from LPS-activated RAW264.7 cells and peritoneal macrophages in a dose-dependent manner. This extract effectively diminished the mRNA levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, implying that the blockade is generated at the transcriptional level. So-EE strongly blocked the activation and translocation of NF-κB and AP-1 by suppressing the upstream kinases including inhibitor of κBα (IκBα), IκBα kinase (IKK), Akt (protein kinase B), phosphoinositide-dependent kinase 1 (PDK1), p85/phosphoinositide-3-kinase (PI3K), and mitogen activated protein kinase (MAPK) such as extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). Moreover, So-EE suppressed the phosphorylation of Src, its kinase activity, and complex formation between Src and p85. CONCLUSION: This study suggests that So-EE has a potent anti-inflammatory activity mediated by NF-κB, and AP-1 inhibitory properties linked to the suppression of Src and MAPK activation.


Asunto(s)
Dinoprostona/antagonistas & inhibidores , FN-kappa B/metabolismo , Óxido Nítrico/antagonistas & inhibidores , Extractos Vegetales/farmacología , Sanguisorba/química , Transducción de Señal/efectos de los fármacos , Factor de Transcripción AP-1/metabolismo , Animales , Western Blotting , Línea Celular , Dinoprostona/biosíntesis , Genes Reporteros , Inmunoprecipitación , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico/biosíntesis , Raíces de Plantas/química
15.
J Agric Food Chem ; 58(19): 10747-51, 2010 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-20843026

RESUMEN

As green tea is being consumed in larger amounts, more green tea waste is being produced. Following extraction, several bioactive compounds may exist in the waste including polyphenols and amino acids. It was found that an Aspergillus niger cellulase treatment of green tea waste increased the extractability of various nutritional and functional components after pretreatments with various extraction solvents such as cold water (CW), hot water (HW), sulfuric acid (SA), hydrochloric acid (HA), and methanol (Me). After the residue was treated with cellulase from Aspergillus niger, the amounts of polyphenols, total catechins, and reducing sugars in the HW extract were increased by 64.6, 941.2, and 350.9%, respectively. In particular, levels of epigallocatechin, epicatechin, and gallic acid were significantly enhanced compared to those in the nontreated control. However, protein extraction was not significantly affected, and cellulase treatment was not more efficient for caffeine extraction compared to phenolic extraction. Among the four extraction solvents, HW and SA showed relatively higher extractabilities as compared to the other groups (CW, HA, and Me). These results indicate that cellulase from A. niger can increase the extractability of green tea waste when combined with certain solvent pretreatments. Consequently, the residual functional compounds and essential nutrients from cellulase-treated green tea waste have the potential to be applied in the production of new functional foods.


Asunto(s)
Aspergillus niger/enzimología , Camellia sinensis/química , Celulasa/farmacología , Extractos Vegetales/química , Hojas de la Planta/química , Catequina/análisis , Pared Celular/metabolismo , Flavonoides/análisis , Manipulación de Alimentos/métodos , Fenoles/análisis , Proteínas de Plantas/análisis , Polifenoles , Solventes
16.
Appl Radiat Isot ; 67(7-8): 1509-12, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19285876

RESUMEN

Although the byproduct from Hizikia fusiformis industry had many nutrients, it is being wasted. In this study, the physiological activities of cooking drip extracts from H. fusiformis (CDHF) were determined to investigate the effect of a gamma and an electron beam irradiations. DPPH radical scavenging activity and tyrosinase and ACE inhibition effects of the gamma and electron beam irradiated CDHF extracts were increased with increasing irradiation dose. These were reasoned by the increase in the content of the total polyphenolic compound of CDHF by the gamma and electron beam irradiation. There were no differences for the radiation types. These results show that ionizing radiation could be used for enhancing the functional activity of CDHF which is a major by-product in Hizikia fusiformis processing, in various applications.


Asunto(s)
Extractos Vegetales/efectos de la radiación , Radiación Ionizante , Inhibidores de la Enzima Convertidora de Angiotensina , Culinaria , Etanol , Industria de Alimentos , Depuradores de Radicales Libres , Monofenol Monooxigenasa/antagonistas & inhibidores
17.
J Med Food ; 12(6): 1343-7, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20041791

RESUMEN

The objective of this study was to evaluate the effect of ionizing radiation on color and antioxidative properties of Chaga mushroom (Inonotus obliquus) extract (CME). CME (10 mg/mL) was gamma-irradiated at 0, 3, 5, 7, and 10 kGy, and color, antioxidant activity, and total phenolic compound levels were then determined. The lightness and yellowness were increased (P < .05), and the redness was decreased (P < .05), as irradiation dose increased. The antioxidant parameters such as the 2-diphenyl-1-picrylhydrazyl, superoxide, and hydroxyl radical scavenging activities, ferric reducing/antioxidant power, and inhibition of lipid peroxidation increased as the irradiation dose increased. Also, the total phenolic compound levels of CME were increased (P < .05) by gamma-irradiation. These results suggest that gamma-irradiation could be considered a means for improving the antioxidant properties and the color of CME.


Asunto(s)
Agaricales/química , Agaricales/efectos de la radiación , Antioxidantes/química , Pigmentación/efectos de la radiación , Rayos gamma , Radical Hidroxilo/química , Peroxidación de Lípido
18.
Opt Express ; 16(19): 14792-800, 2008 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-18795016

RESUMEN

In this paper, we demonstrate that the the bandwidth of the supercontinuum spectrum generated in a large mode area sapphire fiber can be enhanced by employing triple pumping sources. Three pumping sources with wavelengths of 784 nm, 1290 nm, and 2000 nm are launched into a single crystal sapphire fiber that is 5 cm in length and has a core diameter of 115 microm. The nonlinear interactions due to self-phase modulation and four-wave mixing form a broadband supercontinuum that covers the UV, visible, near-IR and lower mid-IR regions. Furthermore, we explore the possibility of generating a broadband supercontinuum expanding from the UV to far-IR region by increasing the number of pumping sources with wavelengths in the mid- and far-IR.


Asunto(s)
Óxido de Aluminio/química , Diseño Asistido por Computadora , Tecnología de Fibra Óptica/instrumentación , Rayos Láser , Iluminación/instrumentación , Modelos Teóricos , Simulación por Computador , Diseño de Equipo , Análisis de Falla de Equipo , Rayos Infrarrojos , Rayos Ultravioleta
19.
Opt Express ; 16(6): 4085-93, 2008 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-18542506

RESUMEN

In this paper, an investigation on broadband IR supercontinuum generation in single crystal sapphire fibers is presented. It is experimentally demonstrated that broadband IR supercontinuum spectrum (up to 3.2microm) can be achieved by launching ultra-short femtosecond laser pulses into single crystal sapphire fiber with a dimension 115microm in diameter and 5cm in length, which covers both the near IR spectral region and the lower end of the mid-IR spectral range. Furthermore, the mechanism of supercontinuum generation in single crystal sapphire fibers is briefly addressed. When the fiber length is shorter than the dispersion length, the self-phase modulation dominates the broadening effect. In this case, the broad supercontinuum spectrum with a smooth profile can be obtained. However, when the fiber length is longer than the dispersion length, the soliton-related dynamics accompanied by the self-phase modulation dominates the broadening effect. There are discrete spikes in the spectrum (corresponding to different order solitons). The above assumption of supercontinuum generation mechanism is quantitatively modeled by the computer simulation program and verified by the experimental results. Thus, one can adjust the spectral profile by properly choosing the length of the sapphire fibers. The broad IR spectral nature of this supercontinuum source can be very useful in a variety of applications such as broadband LADAR, remote sensing, and multi-spectrum free space communications.


Asunto(s)
Óxido de Aluminio/química , Óxido de Aluminio/efectos de la radiación , Tecnología de Fibra Óptica/instrumentación , Rayos Láser , Iluminación/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , Rayos Infrarrojos , Iluminación/métodos
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