RESUMEN
Diabetic neuropathic pain (DNP) is highly common in diabetes patients. P2X receptors play critical roles in pain sensitization. We previously showed that elevated P2X3 expression in dorsal root ganglion (DRG) contributes to DNP. However, the role of other P2X receptors in DNP is unclear. Here, we established the DNP model using a single high-dose streptozotocin (STZ) injection and investigated the expression of P2X genes in the DRG. Our data revealed elevated P2X2, P2X4, and P2X7 mRNA levels in DRG of DNP rats. The protein levels of P2X4 and P2X7 in DNP rats increased, but the P2X2 did not change significantly. To study the role of P2X4 and P2X7 in diabetes-induced hyperalgesia, we treated the DNP rats with TNP-ATP (2',3'-O-(2,4,6-trinitrophenyl)-adenosine 5'-triphosphate), a nonspecific P2X1-7 antagonist, and found that TNP-ATP alleviated thermal hyperalgesia in DNP rats. 2 Hz electroacupuncture is analgesic against DNP and could downregulate P2X4 and P2X7 expression in DRG. Our findings indicate that P2X4 and P2X7 in L4-L6 DRGs contribute to diabetes-induced hyperalgesia, and that EA reduces thermal hyperalgesia and the expression of P2X4 and P2X7.
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Diabetes Mellitus , Neuropatías Diabéticas , Electroacupuntura , Ratas , Animales , Hiperalgesia/metabolismo , Regulación hacia Abajo , Ganglios Espinales/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Neuropatías Diabéticas/metabolismo , Receptores Purinérgicos P2X3/metabolismo , Diabetes Mellitus/metabolismoRESUMEN
Diabetic neuropathic pain (DNP) is a common and destructive complication of diabetes mellitus. The discovery of effective therapeutic methods for DNP is vitally imperative because of the lack of effective treatments. Although 2 Hz electroacupuncture (EA) was a successful approach for relieving DNP, the mechanism underlying the effect of EA on DNP is still poorly understood. Here, we established a rat model of DNP that was induced by streptozotocin (STZ) injection. P2X4R was upregulated in the spinal cord after STZ-injection. The upregulation of P2X4R was mainly expressed on activated microglia. Intrathecal injection of a P2X4R antagonist or microglia inhibitor attenuated STZ-induced nociceptive thermal hyperalgesia and reduced the overexpression of brain-derived neurotrophic factor (BDNF), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the spinal cord. We also assessed the effects of EA treatment on the pain hypersensitivities of DNP rats, and further investigated the possible mechanism underlying the analgesic effect of EA. EA relieved the hyperalgesia of DNP. In terms of mechanism, EA reduced the upregulation of P2X4R on activated microglia and decreased BDNF, IL-1ß and TNF-α in the spinal cord. Mechanistic research of EA's analgesic impact would be beneficial in ensuring its prospective therapeutic effect on DNP as well as in extending EA's applicability.
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OBJECTIVE: The aim of present study was to investigate the efficacy of MXSGT, a traditional Chinese medicine formula used for treatment of respiratory system diseases, in the LPS-induced rat ALI particularly with a focus on its effect on lung microvascular hyperpermeability and inflammatory reaction. METHODS: Male Sprague-Dawley rats were injected with LPS (7.5 mg/kg, 1.5 mg/mL) intraperitoneally. MXSGT (0.52 g or 2.61 g/kg) was given by gavage six hours after LPS injection. RESULTS: LPS stimulation resulted in a reduced survival rate, deteriorated vital signs, an increase in the number of leukocytes adhering to lung venules, the albumin leakage, the activity of MPO in lung tissues, the production of pro-inflammatory cytokines and lung perivascular edema. After LPS stimulation, western blot analysis revealed an increase in the expression of ICAM-1 and toll-like receptor 4, a decrease in tight junction proteins and an activation of cav-1, Src, and NF-κB. All the LPS-induced alterations were significantly attenuated by posttreatment with MXSGT. CONCLUSIONS: This study demonstrated MXSGT as a potential strategy for lung microvascular hyperpermeability and inflammatory reaction in ALI, and suggested that the beneficial role of MXSGT was correlated with toll-like receptor 4, Src, and NF-κB.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Permeabilidad Capilar/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Pulmón/irrigación sanguínea , Microvasos/efectos de los fármacos , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/fisiopatología , Animales , Líquido del Lavado Bronquioalveolar/química , Caveolas/efectos de los fármacos , Adhesión Celular , Citocinas/metabolismo , Esquema de Medicación , Medicamentos Herbarios Chinos/administración & dosificación , Inflamación , Molécula 1 de Adhesión Intercelular/biosíntesis , Molécula 1 de Adhesión Intercelular/genética , Leucocitos , Lipopolisacáridos/toxicidad , Masculino , Microvasos/fisiopatología , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas pp60(c-src)/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Proteínas de Uniones Estrechas/biosíntesis , Proteínas de Uniones Estrechas/genética , Receptor Toll-Like 4/biosíntesis , Receptor Toll-Like 4/genética , Vénulas/efectos de los fármacos , Vénulas/fisiopatologíaRESUMEN
Diabetic neuropathic pain (DNP) is a common complication of diabetes. Streptozotocin (STZ)-induced changes of protein in dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) are critical for DNP genesis. However, which proteins change remains elusive. Here, the DNP model was established by a single intraperitoneal injection of STZ, accompanied by increased fasting blood glucose (FBG), decreased body weight (BW), and decreased paw withdrawal latency (PWL). Proteins change in L4-L6 DRGs and SCDH of rats were detected. Western blot and immunofluorescence results showed that expression levels of phosphorylated protein kinase C (p-PKC), transient receptor potential vanilloid-1 (TRPV1), Substance P (SP) and calcitonin gene-related peptide (CGRP) in the DRG and the SCDH of rats were increased after STZ injection. A preliminary study from our previous study showed that 2 Hz electroacupuncture (EA) effectively alleviates DNP. However, the analgesic mechanism of EA needs further elucidation. Here, EA at the bilateral Zusanli (ST36) and KunLun (BL60) acupoints was applied for one week, and to investigate the effect on DNP. EA reversed thermal hyperalgesia in DNP rats and downregulated the expression of p-PKC, TRPV1, SP, and CGRP in DRG and SCDH.
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OBJECTIVE: To explore the effect of dimethyl sulfoxide(DMSO) on suppressing the release of gut inflammatory cytokine and re-store of the barrier impairment following zymosan-insulted systemic inflammatory response syndrome (SIRS). METHODS: S D rats were randomly divided into four groups:sham with administration of normal saline (SS group); sham with administration of DMSO (DS group); zymosan with administration of normal saline (ZS group); and zymosan with administration of DMSO (ZD group), each group includes two subgroups at 4 h and 24 h after surgery. At 4 h and 24 h after intraperitoneal injection of zymosan (750 mg/kg), the levels of intestinal inflammatory cytokines (tumor necrosis factor-αand interleukin-10) and the activity of diamine oxidase in plasma were examined. Intestinal injury was evaluated by using an intestinal histological score. RESULTS: DMSO suppressed the release of tumor necrosis factor-αand increased interleukin-10 levels in the intestine compared with the ZS group at the corresponding time points. DMSO decreased the level of diamine oxidase in plasma compared with the ZS group. DMSO restored the injury of intestinal villi and the gut injury score was significantly lower than that in the ZS group. CONCLUSIONS: DMSO can suppress the release of intestinal inflammatory cytokines and restore zymosan-insulted gut barrier impairment.
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Dimetilsulfóxido/farmacología , Mucosa Intestinal/efectos de los fármacos , Zimosan/efectos adversos , Amina Oxidasa (conteniendo Cobre)/sangre , Animales , Citocinas/metabolismo , Inflamación , Sustancias Protectoras/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
Frequent and drastic ambient temperature variation may cause respiratory diseases such as common cold and pneumonia, the mechanism for which is not fully understood, however, due to lack of appropriate animal models. Ma-Huang-Tang (MHT) is widely used in China for treatment of respiratory diseases. The present study aimed to investigate the effect of MHT on temperature alternation induced rat lung injury and explore underlying mechanisms. Male Sprague-Dawley rats were exposed to a cold environment for 1 h and then shifted to a warm environment for 30 min. This cold and warm alteration cycled 4 times. Rats were administrated with MHT (1.87 g/kg) by gavage 6 h after cold-warm-cycles. Cold-warm-cycles induced pulmonary microcirculatory disorders, lung edema and injury, decrease in the expression of tight junction proteins, increase in VE-cadherin activation, increase in the expression and activation of Caveolin-1, Src and NF-κB, and NADPH oxidase subunits p47phox, p40phox and p67phox membrane translocation and inflammatory cytokines production. All alterations were significantly ameliorated by post-treatment with MHT. This study showed that rats subjected to cold-warm-cycles may be used as an animal model to investigate ambient temperature variation-induced lung injury, and suggested MHT as a potential strategy to combat lung injury induced by temperature variation.
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Frío , Medicamentos Herbarios Chinos/administración & dosificación , Exposición a Riesgos Ambientales , Calor , Lesión Pulmonar/prevención & control , Animales , Modelos Animales de Enfermedad , Pulmón/patología , Pulmón/efectos de la radiación , Lesión Pulmonar/patología , Ratas Sprague-Dawley , Resultado del TratamientoRESUMEN
By ICP-AES, the authors established the method to quantitatively determine the trace elements Co and Bi in gelatin. The authors processed the unknown sample with wet digesting method. Trace elements in gelatin could be quantitatively determined at the same time. To correct the spectral interference of Fe to Co at specific wavelength, the Interelement Correction(IEC) model was established. The results of the experiment showed that the IEC model could effectively erase the spectral interference of Fe to Co. The result of the spectral correction was greatly superior to the result where the spectral interference weren't corrected by the IEC model. The method was accurate, quick with high performance and wide linear range. The linear correlation coefficient of the tested elements was over 0.999 90. The relative standard deviation (RSD%) was less than 2.00%. The recovery rates were in the range of 98%-107%.
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Bismuto/análisis , Cobalto/análisis , Gelatina/análisis , Espectrofotometría Atómica/métodos , Oligoelementos/análisis , Bismuto/química , Cobalto/química , Gelatina/química , Hierro/química , Modelos Lineales , Reproducibilidad de los Resultados , Oligoelementos/químicaRESUMEN
Change blindness refers to human inability to recognize large visual changes between images. In this paper, we present the first computational model of change blindness to quantify the degree of blindness between an image pair. It comprises a novel context-dependent saliency model and a measure of change, the former dependent on the site of the change, and the latter describing the amount of change. This saliency model in particular addresses the influence of background complexity, which plays an important role in the phenomenon of change blindness. Using the proposed computational model, we are able to synthesize changed images with desired degrees of blindness. User studies and comparisons to state-of-the-art saliency models demonstrate the effectiveness of our model.
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Simulación por Computador , Procesamiento de Imagen Asistido por Computador/métodos , Modelos Biológicos , Trastornos de la Visión , Percepción Visual/fisiología , Adulto , Algoritmos , Análisis de Varianza , Femenino , Humanos , MasculinoRESUMEN
We present PoseShop--a pipeline to construct segmented human image database with minimal manual intervention. By downloading, analyzing, and filtering massive amounts of human images from the Internet, we achieve a database which contains 400 thousands human figures that are segmented out of their background. The human figures are organized based on action semantic, clothes attributes, and indexed by the shape of their poses. They can be queried using either silhouette sketch or a skeleton to find a given pose. We demonstrate applications for this database for multiframe personalized content synthesis in the form of comic-strips, where the main character is the user or his/her friends. We address the two challenges of such synthesis, namely personalization and consistency over a set of frames, by introducing head swapping and clothes swapping techniques. We also demonstrate an action correlation analysis application to show the usefulness of the database for vision application.