- 作者列表："Goodheart AE","Locascio JJ","Samore WR","Collins JA","Brickhouse M","Schultz A","Touroutoglou A","Johnson KA","Frosch MP","Growdon JH","Dickerson BC","Gomperts SN
:Multiple neuropathological processes can manifest in life as a corticobasal syndrome. We sought to relate retention of the tau-PET tracer 18F-AV-1451 and structural magnetic resonance measures of regional atrophy to clinical features in clinically diagnosed and neuropathologically confirmed cases of corticobasal syndrome and to determine whether these vary with the underlying neuropathological changes. In this observational, cross-sectional study, 11 subjects (eight female and three male, median age 72 years) with corticobasal syndrome underwent structural MRI, tau-PET with 18F-AV-1451, amyloid-PET with 11C-Pittsburgh compound B, detailed clinical examinations and neuropsychological testing. Of the 11, three had evidence of high amyloid burden consistent with Alzheimer's disease while eight did not. Neuropathological evaluations were acquired in six cases. Mixed effects general linear models were used to compare 18F-AV-1451 retention and atrophy in amyloid-negative corticobasal syndrome cases to 32 age-matched healthy control subjects and to relate cortical and subcortical 18F-AV-1451 retention and atrophy to clinical features. Subjects without amyloid, including three with pathologically confirmed corticobasal degeneration, showed greater regional 18F-AV-1451 retention and associated regional atrophy in areas commonly associated with corticobasal degeneration pathology than healthy control subjects [retention was higher compared to healthy controls (P = 0.0011), driven especially by the precentral gyrus (P = 0.011) and pallidum (P < 0.0001), and greater atrophy was seen in subjects compared to control subjects (P = 0.0004)]. Both 18F-AV-1451 retention and atrophy were greater in the clinically more affected hemisphere [on average, retention was 0.173 standardized uptake value ratio units higher on the more affected side (95% confidence interval, CI 0.11-0.24, P < 0.0001), and volume was 0.719 lower on the more affected side (95% CI 0.35-1.08, P = 0.0001)]. 18F-AV-1451 retention was greater in subcortical than in cortical regions, P < 0.0001. In contrast to these findings, subjects with amyloid-positive corticobasal syndrome, including two neuropathologically confirmed cases of Alzheimer's disease, demonstrated greater and more widespread 18F-AV-1451 retention and regional atrophy than observed in the amyloid-negative cases. There was thalamic 18F-AV-1451 retention but minimal cortical and basal ganglia uptake in a single corticobasal syndrome subject without neuropathological evidence of tau pathology, likely representing non-specific signal. Asymmetric cortical and basal ganglia 18F-AV-1451 retention consonant with the clinical manifestations characterize corticobasal syndrome due to corticobasal degeneration, whereas the cortical retention in cases associated with Alzheimer's disease is greater and more diffuse.
: 多种神经病理过程可在生活中表现为皮质基底综合征。我们试图将tau-PET示踪剂18F-AV-1451的保留和区域萎缩的结构磁共振测量与皮质基底综合征临床诊断和神经病理学确诊病例的临床特征联系起来，并确定这些特征是否随潜在的神经病理学变化而变化。在这项观察性横断面研究中，11名皮质基底综合征受试者 (8名女性和3名男性，中位年龄72岁) 接受了结构MRI、tau-PET (18F-AV-1451) 、淀粉样蛋白-PET (11C-Pittsburgh compound B) 、详细的临床检查和神经心理测试。在这11人中，3人有与阿尔茨海默病一致的高淀粉样蛋白负担的证据，而8人没有。6例获得神经病理学评价。混合效应一般线性模型用于比较淀粉样蛋白阴性皮质基底综合征病例中的18F-AV-1451保留和萎缩与32名年龄匹配的健康对照受试者，并将皮质和皮质下的18F-AV-1451保留和萎缩与临床特征联系起来。没有淀粉样蛋白的受试者，包括三个病理证实为皮质变性的受试者，在通常与皮质变性病理相关的区域显示出比健康对照受试者更大的区域18F-AV-1451保留和相关的区域萎缩 [保留高于健康对照 (p = 0.0011)，特别是由中央前回驱动 (p = 0.011) 和苍白球 (p <0.0001)，并且与对照受试者相比，在受试者中观察到更大的萎缩 (p = 0.0004)]。18F-AV-1451保留和萎缩在临床上受影响较大的半球中更大 [平均而言，受影响较大的一侧保留为0.173标准化摄取值比单位高 (95% 置信区间，CI 0.11-0.24，p <0.0001)，患侧的体积降低了0.719 (95% CI 0.35-1.08，p = 0.0001)。18F-AV-1451在皮质下的保留大于皮质区，p <0.0001。与这些发现相反，患有淀粉样蛋白阳性皮质基底综合征 (包括两种阿尔茨海默病的神经病理学确诊病例) 的受试者表现出比在淀粉样蛋白阴性病例中观察到的更大且更广泛的18F-AV-1451保留和区域萎缩。在没有tau病理学神经病理学证据的单个皮质基底综合征受试者中存在丘脑18F-AV-1451保留，但皮质和基底神经节摄取很少，可能代表非特异性信号。不对称的皮质和基底神经节18F-AV-1451与临床表现一致的保留是由于皮质退化引起的皮质基底综合征的特征，而与阿尔茨海默病相关的病例的皮质保留更大且更弥漫。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.