- 作者列表："López-García S","Pecci-Lloret MP","García-Bernal D","Guerrero-Gironés J","Pecci-Lloret MR","Rodríguez-Lozano FJ
PURPOSE:To compare the cytotoxicity of six commercially available denture adhesives on human gingival cells: Poligrip Flavour Free Fixative Cream, Fixodent Pro Duo Protection, Novafix cream, FittyDent, Polident Total Action, and Fixodent Pro Plus Duo Protection. MATERIAL AND METHODS:Eluates of denture adhesives were brought into contact with human gingival cells and compared to untreated cells (w/o any dental adhesive elute). Cell toxicity was assessed by measuring cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assays), cell morphology (immunofluorescence assays), induction of apoptosis/necrosis and production of reactive oxygen species (ROS) (flow cytometry assays). In addition, the pH of each sample was determined. Data were analyzed using one-way analysis of variance (ANOVA) followed by Dunnett's multiple comparisons test. RESULTS:All denture adhesives tested led to a reduction in pH, especially Fixodent Pro Duo Protection and Fixodent Pro Plus Duo Protection. The cell viability assays showed that Fixodent Pro Duo Protection (1:1 72 hours, p = 3.04 × 10-6 ; 1:2 72 hours, p = 2.07 × 10-6 ; 1:4 72 hours, p = 2.04 × 10-6 ) and Fixodent Pro Plus Duo Protection (1:1 72 hours, p = 2.01 × 10-6 ; 1:2 72 hours, p = 3.03 × 10-6 ; 1:4 72 hours, p = 2.02 × 10-6 ) significantly decreased cell viability at all dilutions. Compared to the control group and the rest of the adhesives, Poligrip Flavour Free Fixative Cream (PFF 1:1 72 hours, p = 2.24 × 10-6 ; 1:2 72 hours, p = 2.44 × 10-6 ; 1:4 72 hours, p = 2.04 × 10-6 ) showed a significantly higher cell viability score at all dilutions. Fixodent Pro Duo Protection and Fixodent Pro Plus Duo Protection, both adhesives containing zinc salts in their composition, were responsible for necrosis, and the number of cells was much reduced, with aberrant morphology and pyknotic nucleus. Finally, Fixodent (1:2, p = 2.04 × 10-6 , 1:4, p = 0.00036; 1:2, p = 8.82 × 10-6 , 1:4, p = 2.30 × 10-6 ) products significantly promoted ROS production in gingival cells. CONCLUSIONS:The results suggest that denture adhesives containing zinc in their composition could be responsible of the decrease of cell viability, ROS production, aberrant cell morphology, and induction of apoptosis and cell death. However, other possible additional cytotoxic factors must be considered. Thus, more studies are necessary to confirm this hypothesis.
目的: 比较6种市售义齿粘合剂对人牙龈细胞的细胞毒性: Poligrip flamor Free固定剂乳膏、Fixodent Pro Duo保护剂、Novafix乳膏、FittyDent、Polident Total Action和Fixodent Pro Plus Duo保护剂。 材料和方法: 使义齿粘合剂的洗脱液与人牙龈细胞接触，并与未处理的细胞 (没有任何牙科粘合剂洗脱) 进行比较。通过测量细胞活力 (3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物 (MTT) 测定) 、细胞形态 (免疫荧光测定) 、细胞凋亡/坏死的诱导和活性氧 (ROS) 的产生 (流式细胞术测定) 来评估细胞毒性。此外，测定每个样品的pH。使用单因素方差分析 (ANOVA) 分析数据，随后使用Dunnett多重比较检验。 结果: 所有测试的义齿粘合剂导致pH降低，特别是Fixodent Pro Duo保护和Fixodent Pro Plus Duo保护。细胞活力测定显示Fixodent Pro Duo保护 (1:1 72小时，p = 3.04 × 10-6; 1:2 72小时，p = 2.07 × 10-6 ; 1:4 72小时，p = 2.04 × 10-6) 和Fixodent Pro Plus Duo保护 (1:1 72小时，p = 2.01 × 10-6;1:2 72小时，p = 3.03 × 10-6 ; 1:4 72小时，p = 2.02 × 10-6) 在所有稀释度下均显著降低细胞活力。与对照组和其余粘合剂相比，Poligrip无味固定剂霜 (PFF 1:1 72小时，p = 2.24 × 10-6; 1:2 72小时，p = 2.44 × 10-6 ; 1:4 72小时，p = 2.04 × 10-6) 显示在所有稀释度下显著更高的细胞活力评分。Fixodent Pro Duo保护和Fixodent Pro Plus Duo保护，这两种粘合剂在其组成中含有锌盐，是导致坏死的原因，并且细胞数量大大减少，具有异常形态和pyknotic核。最后，Fixodent (1:2，p = 2.04 × 10-6，1:4，p = 0.00036; 1:2，p = 8.82 × 10-6，1:4，p = 2.30 × 10-6) 产物显著促进牙龈细胞中ROS的产生。 结论: 含锌义齿粘接剂的组成可能与细胞活力降低、ROS产生、细胞形态异常以及诱导细胞凋亡和细胞死亡有关。然而，必须考虑其他可能的额外细胞毒性因子。因此，需要更多的研究来证实这一假设。
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.