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Pericardial effusion is a rare but serious complication in cardiac electrophysiology procedures. To avoid progression to acute tamponade and reduce the risk of adverse patient outcomes, emergent pericardiocentesis is often necessary. The conduct of more pericardiocentesis training may further mitigate this risk. However, teaching and practice opportunities are rare, creating the need for pericardiocentesis simulators. While various pericardiocentesis simulators exist, their applications have been limited; further, commercial simulators are anatomically realistic but can be expensive. As such, cheaper homemade simulators have been developed, yet these may lack the cardiac anatomical features for a high-fidelity simulation or may be overly complex to assemble. The purpose of this study is to report initial findings from a pericardiocentesis simulator that incorporates a three-dimensional (3D) cardiac model that is economical, simple to assemble, and anatomically accurate. A 3D-printed cardiac model was printed from a computed tomography file. The model was fitted with a latex balloon-in-a-balloon pericardium filled with colored saline and placed in an ultrasound-compatible gelatin mold to create a pericardiocentesis simulator. The simulator was then tested with experienced and novice trainees at an academic hospital. A total of 10 participants (four interventional cardiology faculty members and six cardiology fellows) performed simulated pericardiocentesis using the simulator and completed a questionnaire to evaluate the model's features and usefulness. The overall feedback regarding this novel simulation approach was positive and the model exhibited important anatomical features to accurately simulate ultrasound-guided pericardiocentesis. All participants were able to successfully insert the needle into the pericardial space and all but one successfully placed the pericardial drain. Survey results indicated that the model was largely perceived as useful for training. This work suggests incorporating a 3D-printed cardiac model into a gelatin mold results in a simple and inexpensive yet high-fidelity pericardiocentesis simulation experience. This novel approach may be useful for teaching pericardiocentesis in an academic hospital.
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Chronic or excess glucocorticoid exposure causes lipid disorders such as hypertriglyceridemia and hepatic steatosis. Angptl4 (angiopoietin-like 4), a primary target gene of the glucocorticoid receptor in hepatocytes and adipocytes, is required for hypertriglyceridemia and hepatic steatosis induced by the synthetic glucocorticoid dexamethasone. Angptl4 has also been shown to be required for dexamethasone-induced hepatic ceramide production. Here, we further examined the role of ceramide-mediated signaling in hepatic dyslipidemia caused by chronic glucocorticoid exposure. Using a stable isotope-labeling technique, we found that dexamethasone treatment induced the rate of hepatic de novo lipogenesis and triglyceride synthesis. These dexamethasone responses were compromised in Angptl4-null mice (Angptl4-/-). Treating mice with myriocin, an inhibitor of the rate-controlling enzyme of de novo ceramide synthesis, serine palmitoyltransferase long-chain base subunit 1 (SPTLC1)/SPTLC2, decreased dexamethasone-induced plasma and liver triglyceride levels in WT but not Angptl4-/- mice. We noted similar results in mice infected with adeno-associated virus-expressing small hairpin RNAs targeting Sptlc2. Protein phosphatase 2 phosphatase activator (PP2A) and protein kinase Cζ (PKCζ) are two known downstream effectors of ceramides. We found here that mice treated with an inhibitor of PKCζ, 2-acetyl-1,3-cyclopentanedione (ACPD), had lower levels of dexamethasone-induced triglyceride accumulation in plasma and liver. However, small hairpin RNA-mediated targeting of the catalytic PP2A subunit (Ppp2ca) had no effect on dexamethasone responses on plasma and liver triglyceride levels. Overall, our results indicate that chronic dexamethasone treatment induces an ANGPTL4-ceramide-PKCζ axis that activates hepatic de novo lipogenesis and triglyceride synthesis, resulting in lipid disorders.
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Proteína 4 Similar a la Angiopoyetina/metabolismo , Ceramidas/metabolismo , Dexametasona/toxicidad , Hígado/efectos de los fármacos , Proteína Quinasa C/metabolismo , Proteína 4 Similar a la Angiopoyetina/deficiencia , Proteína 4 Similar a la Angiopoyetina/genética , Animales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Acido Graso Sintasa Tipo I/genética , Acido Graso Sintasa Tipo I/metabolismo , Ácidos Grasos Monoinsaturados/farmacología , Hígado Graso/etiología , Hígado Graso/metabolismo , Hipertrigliceridemia/etiología , Hipertrigliceridemia/metabolismo , Lipogénesis/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Noqueados , Proteína Quinasa C/antagonistas & inhibidores , Proteína Fosfatasa 2/antagonistas & inhibidores , Proteína Fosfatasa 2/genética , Proteína Fosfatasa 2/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Serina C-Palmitoiltransferasa/antagonistas & inhibidores , Serina C-Palmitoiltransferasa/genética , Serina C-Palmitoiltransferasa/metabolismo , Triglicéridos/sangre , Triglicéridos/metabolismoRESUMEN
Streaming mobile augmented reality applications require both real-time recognition and tracking of objects of interest in a video sequence. Typically, local features are calculated from the gradients of a canonical patch around a keypoint in individual video frames. In this paper, we propose a temporally coherent keypoint detector and design efficient interframe predictive coding techniques for canonical patches, feature descriptors, and keypoint locations. In the proposed system, we strive to transmit each patch or its equivalent feature descriptor with as few bits as possible by modifying a previously transmitted patch or descriptor. Our solution enables server-based mobile augmented reality where a continuous stream of salient information, sufficient for image-based retrieval, and object localization, is sent at a bit-rate that is practical for today's wireless links and less than one-tenth of the bit-rate needed to stream the compressed video to the server.
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Compresión de Datos/métodos , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Fotograbar/métodos , Interfaz Usuario-Computador , Grabación en Video/métodos , Algoritmos , Aumento de la Imagen/métodos , Sistemas en Línea , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por ComputadorRESUMEN
We present the radial gradient transform (RGT) and a fast approximation, the approximate RGT (ARGT). We analyze the effects of the approximation on gradient quantization and histogramming. The ARGT is incorporated into the rotation-invariant fast feature (RIFF) algorithm. We demonstrate that, using the ARGT, RIFF extracts features 16× faster than SURF while achieving a similar performance for image matching and retrieval.
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Algoritmos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Almacenamiento y Recuperación de la Información/métodos , Reconocimiento de Normas Patrones Automatizadas/métodos , Técnica de Sustracción , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Three new phenolic compounds, eurycorymboside A (1), eurycorymboside B (6), and eurycorymbic acid (8), were isolated from the stem part of Eurycorymbus cavaleriei (Sapindaceae) along with five known phenolic compounds, glucosyringic acid (2), vanillic acid 4-O-ß-d-glucoside (3), koaburaside (4), tachioside (5), and 4-hydroxy-3,5-bis(3-methyl-2-butenyl)benzaldehyde (7). The structures were established on the basis of spectral analysis. The antioxidant activities of compounds 1-6 were evaluated by the 1,1-diphenyl-2-picrylhydrazyl-free radical scavenging assay. Compound 4 exhibited antioxidant activity with an IC(50) value of 9.0 µM. Compound 4 also showed weak inhibitory activity against influenza A neuraminidase.
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Antioxidantes/aislamiento & purificación , Antivirales/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Glicósidos/aislamiento & purificación , Fenoles/aislamiento & purificación , Sapindaceae/química , Antioxidantes/química , Antioxidantes/farmacología , Antivirales/química , Antivirales/farmacología , Compuestos de Bifenilo/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Glicósidos/química , Glicósidos/farmacología , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A/enzimología , Neuraminidasa/antagonistas & inhibidores , Fenoles/química , Fenoles/farmacología , Picratos/farmacología , Tallos de la Planta/químicaRESUMEN
AIM OF THE STUDY: Previous studies in our laboratory have shown that total glycosides of peony (TGP) produced antidepressant-like action in various mouse models of behavioral despair. However, the molecular mechanism by which TGP exerts antidepressant-like effect is not fully understood. This study examined the protective effects of TGP against corticosterone-induced neurotoxicity in rat pheochromocytoma (PC12) cells and ts possible mechanisms. MATERIALS AND METHODS: The direct antioxidant effect of TGP was investigated by using a 2,2'-azinobis-(3-ethylbenzothiazoline- 6-sulphonic acid) (ABTS) radical cation-scavenging assay in a cell-free system. PC12 cells were treated with 200 µM of corticosterone in the absence or presence of TGP in varying concentrations for 48 h. Cell viability, lactate dehydrogenase (LDH) activity, intracellular reactive oxygen species (ROS) level, malondialdehyde (MDA) content, glutathione (GSH) content, superoxide dismutase (SOD) activity, and catalase (CAT) activity were then determined. RESULTS: TGP displayed antioxidant properties in the cell-free system, and the IC50 value in the ABTS radical cation-scavenging assay was 9.9 mg/L. TGP treatment at increasing doses (1-10 mg/L) protected against corticosterone-induced cytotoxicity in PC12 cells in a dose-dependent manner. The cytoprotection afforded by TGP treatment was associated with decreases in the intracellular ROS and MDA levels, and increases in the GSH level, SOD activity, and CAT activity in corticosterone-treated PC12 cells. CONCLUSION: The results suggest that TGP has a neuroprotective effect on corticosterone-induced neurotoxicity in PC12 cells, which may be related to its antioxidant action.
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Antioxidantes/farmacología , Muerte Celular/efectos de los fármacos , Corticosterona/farmacología , Glicósidos/farmacología , Paeonia/química , Extractos Vegetales/farmacología , Animales , Catalasa/metabolismo , Glutatión/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Malondialdehído/metabolismo , Células PC12 , Ratas , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Long-term alcohol consumption has been reported to increase oxidative stress in multiple organs and accelerate the aging process. A previous study in our laboratory has shown that Wu-Zi-Yan-Zong-Wan (WZ), a "Yang-invigorating" Chinese herbal formula, protected against ethanol-induced toxicity in HepG2 cells transfected to express human CYP2E1, presumably by enhancing mitochondrial antioxidant status and functional ability. The present study aims to investigate whether WZ extract treatment can afford protection against chronic ethanol-induced oxidative stress (a major risk factor of aging) and mortality in rats. The effect of the extract (1.8 g, 4.5 g, and 9 g raw materials/kg per day) on chronic ethanol hepatotoxicity was investigated in rats receiving steady intragastric infusion of ethanol-containing liquid diet. The results showed that long-term (42 days) herbal co-treatment protected against chronic ethanol-induced mortality and hepatotoxicity and in rats, as evidenced by decreased plasma transaminases activities. The extract also suppressed the pathological development of fatty liver, as assessed by histopathological examination and the ratio of liver weight to body weight. The hepatoprotection afforded by the extract was associated with decreases in the extents of reactive oxygen species production, lipid peroxidation, and oxidative modification of proteins, as well as the reversal of altered mitochondrial reduced glutathione level. The results suggest that the suppressive effect of WZ on chronic ethanol-induced oxidative stress and mortality may be attributed to the antioxidant action, particularly in mitochondria.
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Intoxicación Alcohólica , Medicamentos Herbarios Chinos , Etanol/toxicidad , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Línea Celular , Humanos , Peroxidación de Lípido , Hígado/metabolismo , Hígado/patología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
The Chinese herbal drug Cortex Phellodendri is derived from two species of PHELLODENDRON, P. CHINENSIS Schneid. and P. AMURENSE Rupr. Traditionally, Cortex Phellodendri Chinensis (CPC) and Cortex Phellodendri Amurensis (CPA) are used interchangeably because they are believed to share the same clinical efficacy. Berberine has been believed to be the active ingredient of the herbs. However, recent studies have shown that the content of berberine is much higher in CPC than in CPA. Interestingly, the majority of researches deal with CPA, the one with lower content of berberine. These observations provoke us to reconsider the active ingredients of Cortex Phellodendri. In this study, two traditional usages (antidiarrheal and antibacterial) of Cortex Phellodendri were compared with the chemical analysis of the two herb species used in its formulation. The results suggest that berberine is one of the active ingredients responsible for the antidiarrheal and antibacterial activities of the herbs, but that other chemical ingredients are also involved in regulating the biological actions of the herbal drug. These chemical ingredients may have the same or the opposite effect as berberine. The effectiveness of the herbs is more likely to correlate to the content of total alkaloids rather than to the content of berberine.
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Antibacterianos/farmacología , Antidiarreicos/farmacología , Alcaloides de Berberina/farmacología , Berberina/farmacología , Medicamentos Herbarios Chinos/farmacología , Phellodendron/química , Animales , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antidiarreicos/química , Antidiarreicos/aislamiento & purificación , Berberina/química , Berberina/aislamiento & purificación , Alcaloides de Berberina/química , Alcaloides de Berberina/aislamiento & purificación , Medicamentos Herbarios Chinos/química , Escherichia coli/efectos de los fármacos , Femenino , Motilidad Gastrointestinal/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/efectos de los fármacosRESUMEN
The direction-adaptive partitioned block transform (DA-PBT) is proposed to exploit the directional features in color images to improve coding performance. Depending on the directionality in an image block, the transform either selects one of the eight directional modes or falls back to the nondirectional mode equivalent to the conventional 2-D DCT. The selection of a directional mode determines the transform direction that provides directional basis functions, the block partitioning that spatially confines the high-frequency energy, the scanning order that arranges the transform coefficients into a 1-D sequence for efficient entropy coding, and the quantization matrix optimized for visual quality. The DA-PBT can be incorporated into image coding using a rate-distortion optimized framework for direction selection, and can therefore be viewed as a generalization of variable blocksize transforms with the inclusion of directional transforms and nonrectangular partitions. As a block transform, it can naturally be combined with block-based intra or inter prediction to exploit the directionality remaining in the residual. Experimental results show that the proposed DA-PBT outperforms the 2-D DCT by more than 2 dB for test images with directional features. It also greatly reduces the ringing and checkerboard artifacts typically observed around directional features in images. The DA-PBT also consistently outperforms a previously proposed directional DCT. When combined with directional prediction, gains are less than additive, as similar signal properties are exploited by the prediction and the transform. For hybrid video coding, significant gains are shown for intra coding, but not for encoding the residual after accurate motion-compensated prediction.
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BACKGROUND: The employment of well characterized test samples prepared from authenticated, high quality medicinal plant materials is key to reproducible herbal research. The present study aims to demonstrate a quality assurance program covering the acquisition, botanical validation, chemical standardization and good manufacturing practices (GMP) production of IBS-20, a 20-herb Chinese herbal formula under study as a potential agent for the treatment of irritable bowel syndrome. METHODS: Purity and contaminant tests for the presence of toxic metals, pesticide residues, mycotoxins and microorganisms were performed. Qualitative chemical fingerprint analysis and quantitation of marker compounds of the herbs, as well as that of the IBS-20 formula was carried out with high-performance liquid chromatography (HPLC). Extraction and manufacture of the 20-herb formula were carried out under GMP. Chemical standardization was performed with liquid chromatography-mass spectrometry (LC-MS) analysis. Stability of the formula was monitored with HPLC in real time. RESULTS: Quality component herbs, purchased from a GMP supplier were botanically and chemically authenticated and quantitative HPLC profiles (fingerprints) of each component herb and of the composite formula were established. An aqueous extract of the mixture of the 20 herbs was prepared and formulated into IBS-20, which was chemically standardized by LC-MS, with 20 chemical compounds serving as reference markers. The stability of the formula was monitored and shown to be stable at room temperature. CONCLUSION: A quality assurance program has been developed for the preparation of a standardized 20-herb formulation for use in the clinical studies for the treatment of irritable bowel syndrome (IBS). The procedures developed in the present study will serve as a protocol for other poly-herbal Chinese medicine studies.
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The root part of Paeonia lactiflora Pall., commonly known as peony, is a commonly used Chinese herb for the treatment of depression-like disorders. Previous studies in our laboratory have showed that total glycosides of peony (TGP) produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to investigate the mechanism(s) underlying the antidepressant-like action of TGP by measuring neurotrophins including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in non-stressed and chronic unpredictable mild stress (CUMS)-treated rats. TGP (80 or 160 mg/kg/day) was administered by oral gavage to the animals for 5 weeks. The results showed that CUMS caused depression-like behavior in rats, as indicated by the significant decreases in sucrose consumption and locomotor activity (assessed by open-field test). In addition, it was found that BDNF contents in the hippocampus and frontal cortex were significantly decreased in CUMS-treated rats. CUMS treatment also significantly decreased the level of NGF in the frontal cortex of the animals. Daily intragastric administration of TGP (80 or 160 mg/kg/day) during the five weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. Treating non-stressed animals with TGP (160 mg/kg) for 5 weeks also significantly increased BDNF contents in the hippocampus and frontal cortex, and NGF contents in the frontal cortex. The results suggest that the antidepressant-like action of TGP is mediated, at least in part, by increasing the expression of BDNF and NGF in selective brain tissues.
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Encéfalo/efectos de los fármacos , Depresión/tratamiento farmacológico , Glicósidos/uso terapéutico , Factores de Crecimiento Nervioso/metabolismo , Paeonia/química , Estrés Fisiológico/fisiología , Animales , Encéfalo/metabolismo , Encéfalo/patología , Depresión/etiología , Depresión/metabolismo , Depresión/patología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Conducta Exploratoria/efectos de los fármacos , Privación de Alimentos , Preferencias Alimentarias/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Factores de Crecimiento Nervioso/clasificación , Factores de Crecimiento Nervioso/genética , Fitoterapia , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Sacarosa/administración & dosificación , Edulcorantes/administración & dosificación , Privación de AguaRESUMEN
AIM OF THE STUDY: Wu-Zi-Yan-Zong-Wan (WZ) is a traditional Chinese herbal formula which is commonly used for treating patients with "Yang deficiency". In the present study, the effect of WZ on ethanol-induced toxicity in CYP2E1 cDNA-transfected HepG2 (E47) cells was investigated. MATERIALS AND METHODS: WZ extract was obtained by extracting the herbal powder with 50% ethanol (v/v, in water) and the effect of the extract on ethanol-induced toxicity was investigated in cultured cells. RESULTS: The treatment with WZ extract (12.5-200 microg/mL) for 24h dose-dependently protected against ethanol-induced toxicity in E47 cells, as evidenced by the enhanced cell viability and decreased extent of lactate dehydrogeanse leakage. The cytoprotection against ethanol-induced toxicity was associated with decreases in the extents of reactive oxygen species production and lipid peroxidation, as well as increases in mitochondrial reduced glutathione and membrane potential. In addition, WZ extract treatment also suppressed the formation of DNA fragments in ethanol-intoxicated E47 cells. CONCLUSIONS: WZ extract was found to protect against the ethanol-induced toxicity in E47 cells, possibly by virtues of its antioxidant activity.
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Citocromo P-450 CYP2E1/genética , Medicamentos Herbarios Chinos , Etanol/toxicidad , Estrés Oxidativo/efectos de los fármacos , Línea Celular , ADN Complementario , Humanos , L-Lactato Deshidrogenasa/metabolismo , Peroxidación de Lípido , Potenciales de la Membrana/efectos de los fármacos , Especies Reactivas de Oxígeno , TransfecciónRESUMEN
The root part of Paeonia lactiflora Pall. (Ranunculaceae), commonly known as peony, is a commonly used Chinese herb for the treatment of depression-like disorders. Previous studies in our laboratory have demonstrated that total glycosides of peony (TGP) produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to examine whether TGP could affect the chronic unpredictable mild stress (CUMS)-induced depression in mice. The mechanism(s) underlying the antidepressant-like action was investigated by measuring serum corticosterone level, glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) mRNA levels in brain tissues. CUMS, being lasted for 6 weeks, caused depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Whereas serum corticosterone level was significantly increased in mice exposed to CUMS, expressions of GR mRNA in hippocampus, and BDNF mRNA in hippocampus and frontal cortex, were decreased in CUMS-treated mice. Daily intragastric administration of TGP (80 or 160 mg/kg/day) during the six weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. The results suggest that the antidepressant-like action of TPG is likely mediated by modulating the function of hypothalamic-pituitary-adrenal axis and increasing the expression of BDNF in brain tissues.
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Antidepresivos/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Glicósidos/farmacología , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Paeonia/química , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Estrés Psicológico/fisiopatología , Análisis de Varianza , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Condicionamiento Operante/efectos de los fármacos , Corticosterona/sangre , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática/métodos , Privación de Alimentos , Preferencias Alimentarias/efectos de los fármacos , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Pérdida de Tono Postural/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICR , ARN Mensajero/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Estrés Psicológico/etiología , Estrés Psicológico/metabolismo , Natación , Privación de AguaRESUMEN
ETHNOPHARMACOLOGY RELEVANCE: Peony, the processed root of Paeonia lactiflora Pall. (Ranunculaceae), is a component herb of many traditional formulae for the treatment of depression-like disorders. AIM OF THE STUDY: The present study aimed to investigate whether the total glycosides of peony (TGP) could prevent depression induced by chronic stress. MATERIALS AND METHODS: Mice were subjected to an experimental setting of chronic unpredictable stress (CUS). The effect of TGP treatment on CUS-induced depression was examined by measuring behavioral and neurochemical parameters of depression and the antioxidant status of brain tissue. RESULTS: CUS-induced depression, as indicated by a significant increase in immobility time in the tail suspension test, was associated with increases in the activities of monoamine oxidases, depletion of reduced glutathione, and an increase in malondialdehyde level, in mice brains. TGP treatment alleviated the extent of CUS-induced depression and the associated impairment of antioxidant status in the mouse brain. CONCLUSION: The results suggest that TGP alleviates depression induced by chronic unpredictable stress. The antidepressant-like activity of TGP is probably mediated by inhibition of monoamine oxidases and the attenuation of oxidative stress in mouse brain.
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Antidepresivos/uso terapéutico , Antioxidantes/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Paeonia/química , Fitoterapia , Extractos Vegetales/uso terapéutico , Estrés Psicológico/tratamiento farmacológico , Animales , Antidepresivos/farmacología , Antioxidantes/farmacología , Benzoatos/análisis , Hidrocarburos Aromáticos con Puentes/análisis , Trastorno Depresivo/metabolismo , Glucósidos/análisis , Glutatión/metabolismo , Glicósidos/farmacología , Glicósidos/uso terapéutico , Masculino , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos ICR , Monoaminooxidasa/metabolismo , Monoterpenos , Extractos Vegetales/farmacologíaRESUMEN
Preclinical and clinical investigations have shown the involvement of dysregulation of hypothalamic-pituitary-adrenal (HPA) axis in the pathogenesis of depression. Hypercortisolemia and the associated hippocampal atrophy were observed in patients with depression, which could be ameliorated by the treatment with antidepressants. Therefore, neuroprotection has been proposed to be one of the acting mechanisms of antidepressant. Previous studies in our laboratory have demonstrated the antidepressant-like activity of total glycosides of peony (TGP) in mice. This study aimed to examine the effect of TGP treatment on corticosterone-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. Treating the cells with corticosterone at 200 muM for 48 h caused apoptotic cell death. The cytotoxicity was associated with the activation of caspase-3 activity and the decrease in the mRNA ratio of bcl-2 to bax. TPG treatment at increasing doses (1-10 mg/l) protected against the corticosterone-induced toxicity in PC12 cells in a dose-dependent manner. The cytoprotection afforded by TGP treatment was associated with the inhibition of caspase-3 activity and the up-regulation of bcl-2/bax mRNA ratio. The anti-apoptotic effect of TGP is therefore likely mediated by the suppression of the mitochondrial pathway leading to apoptosis.
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Corticosterona/toxicidad , Glicósidos/farmacología , Neuronas/citología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Paeonia/química , Animales , Caspasa 3/metabolismo , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Células PC12 , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
AIM OF THE STUDY: The root part of Paeonia lactiflora Pall. (Ranunculaceae), known as peony, is often used in Chinese herbal formulae for the treatment of depression-like disorders. Previous studies in our laboratory have shown that an ethanol extract of peony produced antidepressive effects in mouse models of depression. It is well known that peony contains glycosides such as paeoniflorin and albiflorin, yet it remains unclear whether the total glycosides of peony (TGP) are effective. The present study aims to evaluate the antidepressant-like effects of TGP. MATERIALS AND METHODS: The antidepressant-like effects of TGP was determined by using animal models of depression including forced swim and tail suspension tests. The acting mechanism was explored by determining the effect of TGP on the activities of monoamine oxidases. RESULTS: Intragastric administration of TGP at 80 and 160 mg/kg for seven days caused a significant reduction of immobility time in both forced swim and tail suspension tests, yet TGP did not stimulate locomotor activity in the open-field test. In addition, TGP treatment antagonized reserpine-induced ptosis and inhibited the activities of monoamine oxidases in mouse cerebrum. CONCLUSION: These results suggest that the antidepressive effects of TGP are mediated, at least in part, by the inhibition of monoamine oxidases.
Asunto(s)
Antidepresivos/farmacología , Depresión/tratamiento farmacológico , Glicósidos/farmacología , Paeonia/química , Animales , Antidepresivos/administración & dosificación , Antidepresivos/aislamiento & purificación , Conducta Animal/efectos de los fármacos , Blefaroptosis/inducido químicamente , Blefaroptosis/tratamiento farmacológico , Cerebro/efectos de los fármacos , Cerebro/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Glicósidos/administración & dosificación , Glicósidos/aislamiento & purificación , Masculino , Ratones , Ratones Endogámicos ICR , Monoaminooxidasa/efectos de los fármacos , Monoaminooxidasa/metabolismo , Actividad Motora/efectos de los fármacos , Extractos Vegetales/farmacología , Reserpina , NataciónRESUMEN
BACKGROUND: Therapeutic intervention in many neurological diseases is thwarted by the physical obstacle formed by the blood-brain barrier (BBB) that excludes most drugs from entering the brain from the blood. Thus, identifying efficacious modes of drug delivery to the brain remains a "holy grail" in molecular medicine and nanobiotechnology. Brain capillaries, that comprise the BBB, possess an endogenous receptor that ferries an iron-transport protein, termed p97 (melanotransferrin), across the BBB. Here, we explored the hypothesis that therapeutic drugs "piggybacked" as conjugates of p97 can be shuttled across the BBB for treatment of otherwise inoperable brain tumors. APPROACH: Human p97 was covalently linked with the chemotherapeutic agents paclitaxel (PTAX) or adriamycin (ADR) and following intravenous injection, measured their penetration into brain tissue and other organs using radiolabeled and fluorescent derivatives of the drugs. In order to establish efficacy of the conjugates, we used nude mouse models to assess p97-drug conjugate activity towards glioma and mammary tumors growing subcutaneously compared to those growing intracranially. PRINCIPAL FINDINGS: Bolus-injected p97-drug conjugates and unconjugated p97 traversed brain capillary endothelium within a few minutes and accumulated to 1-2% of the injected by 24 hours. Brain delivery with p97-drug conjugates was quantitatively 10 fold higher than with free drug controls. Furthermore, both free-ADR and p97-ADR conjugates equally inhibited the subcutaneous growth of gliomas growing outside the brain. Evocatively, only p97-ADR conjugates significantly prolonged the survival of animals bearing intracranial gliomas or mammary tumors when compared to similar cumulated doses of free-ADR. SIGNIFICANCE: This study provides the initial proof of concept for p97 as a carrier capable of shuttling therapeutic levels of drugs from the blood to the brain for the treatment of neurological disorders, including classes of resident and metastatic brain tumors. It may be prudent, therefore, to consider implementation of this novel delivery platform in various clinical settings for therapeutic intervention in acute and chronic neurological diseases.
Asunto(s)
Antineoplásicos/administración & dosificación , Barrera Hematoencefálica , Portadores de Fármacos , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapéutico , Colorantes Fluorescentes , Humanos , Ratones , Ratones Desnudos , Paclitaxel/administración & dosificación , Paclitaxel/farmacocinética , Paclitaxel/uso terapéuticoRESUMEN
The human kallikrein 8 protein (KLK8) is expressed in many normal tissues including esophagus, skin, testis, tonsil, kidney, breast, and salivary gland, and is found in biological fluids including breast milk, amniotic fluid, seminal fluid and serum. It has also been shown to be a biomarker and prognostic factor for breast cancer. The aim of this study was to determine whether KLK8 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas, adenoid cystic carcinomas, polymorphous low grade adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas, and adenocarcinomas NOS of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors show high levels of expression of KLK8.
Asunto(s)
Adenocarcinoma/metabolismo , Adenoma Pleomórfico/metabolismo , Calicreínas/metabolismo , Neoplasias de las Glándulas Salivales/metabolismo , Glándulas Salivales Menores/metabolismo , Adenocarcinoma/patología , Adenoma Pleomórfico/patología , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Acinares/metabolismo , Carcinoma de Células Acinares/patología , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Adenoide Quístico/patología , Humanos , Técnicas para Inmunoenzimas , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales Menores/patologíaRESUMEN
The blood-brain barrier (BBB) performs a neuroprotective function by tightly controlling access to the brain; consequently it also impedes access of proteins as well as pharmacological agents to cerebral tissues. We demonstrate here that recombinant human melanotransferrin (P97) is highly accumulated into the mouse brain following intravenous injection and in situ brain perfusion. Moreover, P97 transcytosis across bovine brain capillary endothelial cell (BBCEC) monolayers is at least 14-fold higher than that of holo-transferrin, with no apparent intra-endothelial degradation. This high transcytosis of P97 was not related to changes in the BBCEC monolayer integrity. In addition, the transendothelial transport of P97 was sensitive to temperature and was both concentration- and conformation-dependent, suggesting that the transport of P97 is due to receptor-mediated endocytosis. In spite of the high degree of sequence identity between P97 and transferrin, a different receptor than the one for transferrin is involved in P97 transendothelial transport. A member of the low-density lipoprotein receptor protein family, likely LRP, seems to be involved in P97 transendothelial transport. The brain accumulation, high rate of P97 transcytosis and its very low level in the blood suggest that P97 could be advantageously employed as a new delivery system to target drugs directly to the brain.