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Role of group II and group III metabotropic glutamate receptors in spinal cord injury. 总被引:4,自引:0,他引:4
Spinal cord injury (SCI) produces an increase in extracellular excitatory amino acid (EAA) concentrations that results in glutamate receptor-mediated excitotoxic events. An important class of these receptors is the metabotropic glutamate receptors (mGluRs). mGluRs can activate a number of intracellular pathways that increase neuronal excitability and modulate neurotransmission. Group I mGluRs are known to modulate EAA release and the development of chronic central pain (CCP) following SCI; however, the role of group II and III mGluRs remains unclear. To begin evaluating group II and III mGluRs in SCI, we administered the specific agonists for group II, APDC, or group III, L-AP4, by interspinal injection immediately following SCI. Contusion injury was produced at spinal segment T10 with a New York University impactor (12.5-mm drop, 10-g rod 2 mm in diameter) in 30 adult male Sprague-Dawley rats (175-200 g). Evoked and spontaneous behavioral measures of CCP, locomotor recovery, changes in mGluR expression, and amount of spared tissue were examined. Neither APDC nor L-AP4 affected locomotor recovery or the development of thermal hyperalgesia; however, L-AP4 and APDC attenuated changes in mechanical thresholds and changes in exploratory behavior indicative of CCP. APDC- and L-AP4-treated groups had higher expression levels of mGluR2/3 at the epicenter of injury on post contusion day 28; however, there was no difference in the amount of spared tissue between treatment groups. These results demonstrate that treatment with agonists to group II and III mGluRs following SCI affects mechanical responses, exploratory behavior, and mGluR2/3 expression without affecting the amount of tissue spared, suggesting that the level of mGluR expression after SCI may modulate nociceptive responses. 相似文献
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Elise Chiffoleau Gaëlle Bériou Patrick Dutartre Claire Usal Jean-Paul Soulillou Maria Cristina Cuturi 《American journal of transplantation》2002,2(8):745-757
A 20-day treatment with LF15-0195, a deoxyspergualine analog, induced long-term heart allograft survival in the rat without signs of chronic rejection. LF15-0195-treated recipients did not develop an anti-donor alloantibody response. Analysis of graft-infiltrating cells, IL10, TNFalpha, IFNgamma mRNA and iNOS protein expression in allografts, 5 days after transplantation, showed that they were markedly decreased in allografts from LF15-0195-treated recipients compared with allografts from untreated recipients. Surprisingly, spleen T cells from LF15-0195 recipients, 5days after grafting, were able to proliferate strongly in vitro, when stimulated with donor cells, but had reduced mRNA expression for IFNy compared with spleen T cells from untreated graft recipients. Furthermore, when T cells from naive animals were stimulated in vitro, using anti-CD3 and anti-CD28, LF15-0195 also increased T-cell proliferation in a dose-dependent fashion: however, these cells expressed less of the Th1 -related cytokines, IFNgamma and IL2, compared with untreated cells, suggesting that LF15-0195 could act on T-cell differentiation. In conclusion, we show here that a short-term treatment with LF15-0195 induced long-term allograft tolerance, decreasing the in situ anti-donor response, and we illustrate evidence for the development of regulatory mechanisms. 相似文献
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Augusto Giussani Adeseye M Arogunjo Marie Claire Cantone Federico Tavola Ivan Veronese 《Applied radiation and isotopes》2006,64(6):639-644
The intestinal absorption of molybdenum in healthy human volunteers has been measured by simultaneous oral and intravenous administration of the stable isotopes 95Mo and 96Mo, and the results were analysed using the convolution integral technique. The results showed that molybdenum ingested in liquid form was rapidly and totally absorbed into the circulation under ordinary intake regimes. The rates and extent of absorption were lower for composite meals, and also for increasing levels of administration. This information can be helpful in the application of the new ICRP model of the human alimentary tract. 相似文献
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Alex W Wilson Stephen J Medhurst Claire I Dixon Nick C Bontoft Lisa A Winyard Kim T Brackenborough Jorge De Alba Christopher J Clarke Martin J Gunthorpe Gareth A Hicks Chas Bountra Daniel S McQueen Iain P Chessell 《European Journal of Pain》2006,10(6):537-549
Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic. 相似文献
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Background: The slitlamp can be used to estimate the anterior chamber depth (ACD). The length of a slit object is increased until the corneal and iris/lens images appear to just touch. Multiplying the just‐touching‐slit‐length (JTSL) by a conversion factor gives an estimate of the ACD as measured by ultrasonography. The purpose of this study was to determine if central corneal thickness (CCT) affects the accuracy of this technique. Methods: The ACD of 50 subjects was measured by A‐scan ultrasonography and estimated by the slitlamp technique. CCT was measured by ultrasonic pachometry. The refractive error was determined subjectively. Results: The average ultrasonographic ACD for all subjects was 3.32 ± 0.65 mm. The average JTSL was 2.46 ± 0.38 mm. The conversion ratio between the ultrasonographic ACD and the average JTSL was 1.35. The predicted ACD using the regression equation of JTSL on the ultrasound anterior chamber depth (USACD) was 3.32 ± 0.54 mm. The corresponding value using the regression equation of JTSL and CCT on USACD was exactly the same, that is, 3.32 ± 0.54 mm. Conclusion: Incorporation of CCT into a regression equation does not improve the accuracy of the Smith technique. 相似文献
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Changes in the design of hospital wards have usually been determined by architects and members of the nursing and medical professions, the views and preferences of patients have seldom been sought directly The Hospital Anxiety and Depression scale and the Disturbance Due to Hospital Noise questionnaire were administered to 64 female patients on bay and Nightingale wards together with a questionnaire designed for this study Perceptions of social and physical factors of ward design were examined, and their relationship to psychological well-being and sleep patterns The results show that the bay ward seemed to offer a more favourable environment for patients but some of the disadvantages of bay wards are balanced by better staffing levels and better and more modern facilities Visibility to nurses was lower on the bay ward The Nightingale ward was perceived as significantly noisier than the bay ward and noise levels were significantly correlated to anxiety scores Paradoxically the increase in noise levels appeared to improve the perceived level of privacy on the Nightingale ward Seventy-five per cent of patients were found to prefer the bay ward design, and since neither design appears to have major disadvantages their continued introduction should be encouraged However, recommendations are made concerning the optimizing of patients' well-being within the bay ward setting 相似文献