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91.
Effect of lumbar 5 ventral root transection on pain behaviors: a novel rat model for neuropathic pain without axotomy of primary sensory neurons 总被引:13,自引:0,他引:13
A peripheral nerve injury often causes neuropathic pain but the underlying mechanisms remain obscure. Several established animal models of peripheral neuropathic pain have greatly advanced our understanding of the diverse mechanisms of neuropathic pain. A common feature of these models is primary sensory neuron injury and the commingle of intact axons with degenerating axons in the sciatic nerve. Here we investigated whether neuropathic pain could be induced without sensory neuron injury following exposure of their peripheral axons to the milieu of Wallerian degeneration. We developed a unilateral lumbar 5 ventral root transection (L5 VRT) model in adult rats, in which L5 ventral root fibers entering the sciatic nerve were sectioned in the spinal canal. This model differs from previous ones in that DRG neurons and their afferents are kept uninjured and intact afferents expose to products of degenerating efferent ventral root fibers in the sciatic nerve and the denervated muscles. We found that the L5 VRT produced rapid (24 h after transection), robust and prolonged (56 days) bilateral mechanical allodynia, to a similar extent to that in rats with L5 spinal nerve transection (L5 SNT), cold allodynia and short-term thermal hyperalgesia (14 days). Furthermore, L5 VRT led to significant inflammation as demonstrated by infiltration of ED-1-positive monocytes/macrophages in the DRG, sciatic nerve and muscle fibers. These findings demonstrated that L5 VRT produced behavioral signs of neuropathic pain with high mechanical sensitivity and thermal responsiveness, and suggested that neuropathic pain can be induced without damage to sensory neurons. We propose that neuropathic pain in this model may be mediated by primed intact sensory neurons, which run through the milieu of Wallerian degeneration and inflammation after nerve injury. The L5 VRT model manifests the complex regional pain syndrome in some human patients, and it may provide an additional dimension to dissect out the mechanisms underlying neuropathic pain. 相似文献
92.
Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription 总被引:23,自引:0,他引:23
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93.
Magudumana MO Ballot DE Cooper PA Trusler J Cory BJ Viljoen E Carter AC 《Journal of tropical pediatrics》2000,46(5):267-271
The objective of the present study was to evaluate serial interleukin 6 (IL6) levels in the early diagnosis of neonatal sepsis. Subjects included 255 neonates from the Neonatal Unit of Johannesburg Hospital evaluated for suspected sepsis between February and May 1998. All infants had IL6, full blood count (FBC), C reactive protein (CRP) and blood cultures done at presentation. CRP and IL6 were repeated after 24 h. Infants were categorized into groups according to the likelihood of infection on the basis of clinical presentation, CRP, FBC and culture results, i.e., group 1 (no infection) to group 4 (definite infection). IL6 was compared between the groups by the U-test of Mann-Whitney; stepwise logistic regression was done to establish the best predictors of infection, sensitivity, specificity, positive and negative predictive values were determined. The initial IL6 level was significantly raised in those infants with possible infection [880.67 pg/ml (2966.04), p value 0.0104], probable infection [422.62pg/ml (4077.7), p value 0.0021] and definite infection [11164.39pg/ml (24139.77), p value 0.0000] as compared to those infants without infection [58.65 (182.4)]. The best predictors of infection were the combination of the initial IL6 value and CRP value after 24 h (goodness of fit 97.7 per cent). An initial IL6 value below 20 pg/ml gave a negative predictive value of 90.18 per cent. It is concluded that an IL6 value done at the time of presentation of signs and symptoms suggestive of infection is useful in the early diagnosis of neonatal sepsis. In particular, an initial IL6 value below 20 pg/ml may allow antibiotics to be withheld in a number of infants evaluated for sepsis. There is no benefit in serial determination of IL6 in the diagnosis of neonatal sepsis. 相似文献
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96.
Zinc Gluconate Lozenges for Treating the Common Cold in Children: A Randomized Controlled Trial 总被引:3,自引:0,他引:3
Macknin Michael L.; Piedmonte Marion; Calendine Cory; Janosky Janine; Wald Ellen 《JAMA》1998,279(24):1962-1967
Context. The common cold is one of the most frequently occurring illnesses and is responsible for substantial morbidity and economic loss. Biochemical evidence suggests that zinc may be an effective treatment, and zinc gluconate glycine (ZGG) lozenges have been shown to reduce the duration of cold symptoms in adults. Objective. To determine the efficacy of ZGG treatment of colds in children and adolescents. Design. A randomized, double-masked, placebo-controlled study. Setting. Two suburban school districts in Cleveland, Ohio. Patients. A total of 249 students in grades 1 through 12 were enrolled within the first 24 hours of experiencing at least 2 of 9 symptoms of the common cold. Intervention. Zinc lozenges, 10 mg, orally dissolved, 5 times a day (in grades 1-6) or 6 times a day (in grades 7-12). Main Outcome Measures. Time to resolution of cold symptoms based on subjective daily symptom scores for cough, headache, hoarseness, muscle ache, nasal congestion, nasal drainage, scratchy throat, sore throat, and sneezing. Results. Time to resolution of all cold symptoms did not differ significantly between students receiving zinc (n=124) and those receiving placebo (n=125) (median, 9 days; 95% confidence interval [CI], 8-9 days; median, 9 days, 95% CI, 7-10 days, respectively; P=.71). There were no significant differences in the time to resolution of any of the 9 symptoms studied. Compared with controls, more students in the zinc group reported adverse effects (88.6% vs 79.8%; P=.06); bad taste (60.2% vs 37.9%; P=.001); nausea (29.3% vs 16.1%; P=.01); mouth, tongue, or throat discomfort (36.6% vs 24.2%; P=.03); and diarrhea (10.6% vs 4.0%; P=.05). Conclusions. In this community-based, randomized controlled trial, ZGG lozenges were not effective in treating cold symptoms in children and adolescents. Further studies with virologic testing are needed to clarify what role, if any, zinc may play in treating cold symptoms. 相似文献
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98.
T-cell lymphomas mask slower developing B-lymphoid and myeloid tumours in transgenic mice with broad haemopoietic expression of MYC 总被引:2,自引:0,他引:2
Deregulation of MYC expression occurs in many haematological malignancies. Previous studies modelling MYC-induced lymphomagenesis in the mouse used transgenic vectors that directed MYC overexpression in a lineage-specific manner. Here, we describe a transgenic mouse strain in which constitutive MYC expression is driven broadly in haemopoiesis by a vector containing regulatory elements of the Vav gene. Healthy young VavP-MYC17 mice had multiple haemopoietic abnormalities, most notably increased size and numbers of B-lymphoid cells, monocytes and megakaryocytes. The mice rapidly developed tumours and, surprisingly, these were exclusively T-cell lymphomas, mostly of mature CD4(+) CD8(-) T cells, a tumour type that is seldom seen in mouse models. To examine tumour development in the absence of the susceptible T cells, we bred VavP-MYC17 mice lacking the Rag1 recombinase. They survived longer and succumbed to tumours of several different haemopoietic cell types: pre-T cells, pro-B cells, macrophages and unusual progenitor cells. Thus, although T-lineage cells have the shortest latent period to transformation, the VavP-MYC17 transgene drives malignant transformation of multiple cell types and VavP-MYC17 mice provide a new model for tumours of multiple haemopoietic lineages. 相似文献
99.
Killing cancer cells by flipping the Bcl-2/Bax switch 总被引:21,自引:0,他引:21
Impairment of apoptosis, the physiologic cell death process, is central to cancer development and renders tumors refractory to cytotoxic therapy. Bcl-2, the oncoprotein activated in follicular lymphoma, inhibits the conserved cell death pathway triggered by diverse cytotoxic agents, as do several close relatives. A small-molecule antagonist of these proteins has now been designed by Oltersdorf et al. Strikingly, ABT-737 sensitizes many tumors to cytotoxic agents and is effective as a single agent against certain lymphomas and solid tumors, provoking stable regression in some tumor xenografts. Hence, this work validates Bcl-2-like proteins as important new targets in cancer therapy. 相似文献
100.
Paterson NE Bruijnzeel AW Kenny PJ Wright CD Froestl W Markou A 《Neuropharmacology》2005,49(7):953-962
Gamma-aminobutyric acid subtype B (GABA(B)) receptors play an important role in regulating brain reward function. Accumulating evidence suggests that chronic exposure to drugs of abuse may alter GABA(B) receptor function. The present studies investigated whether chronic nicotine administration, using a regimen that induces nicotine dependence, increased inhibitory regulation of brain reward function by GABA(B) receptors, as measured by intracranial self-stimulation (ICSS) thresholds in rats. Such an action of nicotine may contribute to the reward deficit observed during nicotine withdrawal. Nicotine-dependent and control rats received the GABA transaminase inhibitor gamma-vinyl-GABA or the GABA(B) receptor agonist CGP44532 according to a within-subjects Latin square design, and ICSS thresholds were assessed post-injection. Systemic administration of the lowest doses of GVG or CGP44532 did not alter reward thresholds in control or nicotine-treated rats, whereas the highest doses of each drug elevated thresholds similarly in both groups. Further, micro-infusion of CGP44532 directly into the ventral tegmental area elevated ICSS thresholds similarly in saline- and nicotine-treated rats. Overall, these data demonstrate that prolonged nicotine exposure did not alter GABA(B) receptor-mediated regulation of brain reward function, and suggest that alterations in GABA(B) receptor activity are unlikely to play a role in the brain reward deficits associated with spontaneous nicotine withdrawal. 相似文献