Scientific reports
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Degeneration of dopaminergic neurons causes Parkinson's disease. Dopamine replacement therapy with L-DOPA is the best available treatment. However, patients develop L-DOPA-induced dyskinesia (LID). ⋯ GRK3, kinase-dead GRK3, and RH inhibited accumulation of ∆FosB, a marker of LID. RH-dead mutant was ineffective, whereas GRK3 knockdown exacerbated ∆FosB accumulation. Our findings reveal a novel mechanism of GRK3 control of the dopamine receptor signaling and the role of Gq in LID.
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Meta Analysis
A comparision of nalbuphine with morphine for analgesic effects and safety : meta-analysis of randomized controlled trials.
Although morphine is the standard opioid analgesic for pain control and has been widely used, certain drug-induced adverse effects have been reported as intolerable and need to be addressed. Nalbuphine may have a few advantages over morphine in this respect. We aimed to describe the effect of nalbuphine as well as its safety compared to morphine by analyzing published randomized controlled trials (RCTs) with meta-analysis approach. ⋯ Overall, there was no evidence to show that the effect of pain relief had any difference between nalbuphine and morphine (pooled relative risks [RRs], 1.01; 95% CI, 0.91 to 1.11; P = 0.90). On the other hand, the incidences of pruritus, nausea, vomiting, respiratory depression were significantly lower in nalbuphine group compared with morphine group, and the pooled RRs were 0.78(95%CI, 0.602-0.997; P = 0.048) for nausea, 0.65(95%CI, 0.50-0.85; P = 0.001) for vomiting, 0.17(95%CI, 0.09-0.34; P < 0.0001) for pruritus, and 0.27(95%CI, 0.12-0.57; P = 0.0007) for respiratory depression. The analgesic efficacy of nalbuphine is comparable to morphine, but nalbuphine provides a better safety profile than morphine in the aspect of certain side-effects, especially related to pruritus and respiratory depression.
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Macaque monkeys with a unilateral lesion in V1 have been used as an animal model of blindsight. While objective proof of blindsight requires that the two aspects of blindsight (residual forced-choice localization and attenuated yes-no detection) should be tested under identical stimulus conditions using bias-free measures of sensitivity, these have not been attained in studies of nonhuman primates. Here we tested two macaque monkeys with a unilateral V1 lesion with two saccade tasks using identical stimuli: a forced-choice (FC) task and a yes-no (YN) task. ⋯ Such dissociation of sensitivity between the two tasks was not observed when near-threshold visual stimuli were presented in the normal, unaffected hemifield. These results suggest that the V1-lesioned monkeys resemble the well-studied blindsight patient G. Y., whose visual experience per se was completely abolished.
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Silent information regulator type-1 (SIRT1) has been reported to be involved in the cardiopulmonary protection. However, its role in the pathogenesis of burn-induced remote acute lung injury (ALI) is currently unknown. The present study aims to investigate the role of SIRT1 in burn-induced remote ALI and the involved signaling pathway. ⋯ We next used primary pulmonary microvascular endothelial cells (PMVECs) challenged by burn serum (BS) to simulate in vivo rat lung tissue after burn injury, and found that BS significantly suppressed SIRT1 expression, increased cell apoptosis, and activated p38 MAPK signaling. The use of resveratrol reversed these effects, while knockdown of SIRT1 by shRNA further augmented BS-induced increase of cell apoptosis and activation of p38 MAPK. Taken together, these results indicate that SIRT1 might protect lung tissue against burn-induced remote ALI by attenuating PMVEC apoptosis via p38 MAPK signaling, suggesting its potential therapeutic effects on the treatment of ALI.
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Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. Neuroinflammation has been recognized to play an important role in the pathogenesis of various diseases in the central nervous system. Here we investigated the anti-nociceptive and anti-neuroinflammatory effect of curcumin on arthritic pain in rats. ⋯ Furthermore, such a curcumin treatment reduced CFA-induced activation of glial cells and production of inflammatory mediators [interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and monocyte inflammatory protein-1 (MIP-1α)] in the spinal cord. Curcumin also decreased lipopolysaccharide-induced production of IL-1β, tumor necrosis factor-α, MCP-1, and MIP-1α in cultured astrocytes and microglia. Our results suggest that intrathecal curcumin attenuates arthritic pain by inhibiting glial activation and the production of inflammatory mediators in the spinal cord, suggesting a new application of curcumin for the treatment of arthritic pain.