- 作者列表："França de Souza D","Alonso MA","Brito MM","Meirelles MG","Francischini MCP","Nichi M","Fernandes CB
BACKGROUND:In newborns, exposure to the extrauterine environment with high oxygen tension and sudden pulmonary adaptation leads to an increase in reactive oxygen species (ROS). ROS have several physiological roles, which are essential for neonatal development, however, when unbalanced, these highly unstable molecules can cause cellular destabilisation, compromising vital processes. OBJECTIVES:To characterise the oxidative status in healthy equine neonates, evaluating an indicator of lipid peroxidation and both enzymatic and nonenzymatic antioxidant systems, during the first week of life. STUDY DESIGN:Experimental cohort. METHODS:Twenty-four foals were evaluated, with blood collections performed at 5 minutes, 12, 72 and 168 hours after birth. The degree of lipid peroxidation was quantified using Thiobarbituric Acid Reactive Substances (TBARS). Superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic activities, and total, conjugated and unconjugated serum bilirubin levels were also analysed. Comparisons were performed using ANOVA followed by a Tukey's test. Additionally, dependent variables were also evaluated with Pearson's correlation tests. RESULTS:Higher GPx activity was observed at 12 and 72 hours when compared to 5 minutes. An increase in TBARS levels was found at 5 minutes after birth, followed by a decrease at 72 hours and stabilisation through subsequent moments until 168 hours after birth. No differences were observed in SOD activity when comparing the four time points. Bilirubin concentrations were lower at 5 minutes after birth and total and unconjugated bilirubin increased at 12 hours and decreased between 72 and 168 hours after birth. CONCLUSIONS:Lipid peroxidation at birth was high, suggesting an increase in ROS levels relating to physiological events in neonatal adaptation. Antioxidant systems, involving unconjugated bilirubin and GPx, were activated and these biomolecules act concomitantly to reduce ROS levels, thus maintaining oxidative homeostasis. Overall, our results suggest a pro-oxidant balance during the first 168 hours after birth in equine neonates.
背景: 在新生儿中，暴露于高氧张力的宫外环境和突然的肺适应导致活性氧 (ROS) 增加。ROS具有几种生理作用，这对新生儿发育至关重要，然而，当不平衡时，这些高度不稳定的分子会导致细胞不稳定，损害重要过程。 目的: 描述健康马新生儿的氧化状态，评估生命第一周脂质过氧化和酶和非酶抗氧化系统的指标。 研究设计: 实验队列。 方法: 对24只马驹进行评估，在出生后5分钟、12、72和168小时进行采血。使用硫代巴比妥酸反应性物质 (TBARS) 定量脂质过氧化的程度。还分析了超氧化物歧化酶 (SOD) 和谷胱甘肽过氧化物酶 (GPx) 酶活性以及总、结合和非结合血清胆红素水平。使用ANOVA进行比较，随后进行Tukey检验。此外，还使用Pearson相关检验评估因变量。 结果: 与5分钟相比，在12和72小时观察到更高的GPx活性。在出生后5分钟发现TBARS水平增加，随后在72小时下降，并在随后的时刻保持稳定，直到出生后168小时。当比较四个时间点时，没有观察到SOD活性的差异。出生后5分钟时胆红素浓度较低，12小时时总胆红素和非结合胆红素增加，出生后72至168小时下降。 结论: 出生时脂质过氧化高，表明与新生儿适应中的生理事件相关的ROS水平增加。涉及未结合胆红素和GPx的抗氧化系统被激活，并且这些生物分子同时起作用以降低ROS水平，从而维持氧化稳态。总体而言，我们的研究结果表明，马新生儿在出生后的前168小时内存在促氧化平衡。
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.