- 作者列表："Bonfanti R","Iafusco D","Rabbone I","Diedenhofen G","Bizzarri C","Patera PI","Reinstadler P","Costantino F","Calcaterra V","Iughetti L","Savastio S","Favia A","Cardella F","Lo Presti D","Girtler Y","Rabbiosi S","D'Annunzio G","Zanfardino A","Piscopo A","Casaburo F","Pintomalli L","Russo L","Grasso V","Minuto N","Mucciolo M","Novelli A","Marucci A","Piccini B","Toni S","Silvestri F","Carrera P","Rigamonti A","Frontino G","Trada M","Tinti D","Delvecchio M","Rapini N","Schiaffini R","Mammì C","Barbetti F","Diabetes Study Group of ISPED.
Objective:Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design:Retrospective analysis of the Italian data set of patients with TNDM. Methods:Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared. Results:Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; -2.27 SD) than those with KATP mutations (4.0 weeks; -1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions:If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.
目的: 短暂性新生儿糖尿病 (TNDM) 是由ABCC8和KCNJ11基因激活突变 (KATP/TNDM) 或染色体6q24异常 (6q24/TNDM) 引起的。我们想评估这些不同的遗传病因是否导致不同的临床特征。 设计: 意大利TNDM患者数据集的回顾性分析。 方法: 对22例KATP/TNDM患者和12例6q24/TNDM患者的临床特点和治疗进行比较。 结果: 14例KATP/TNDM先证者父母中有1例血糖异常，4例6q24表现为巨舌症和/或脐疝。6q24 (1周; -2.27 SD) 患者的糖尿病发病的中位年龄和出生体重低于KATP突变患者 (4.0周; -1.04 SD) (分别为P = 0.009和P = 0.007)。KATP/TNDM的中位缓解时间长于6q24/TNDM (21.5周vs 12周) (P = 0.002)。两名KATP/TNDM患者在没有药物治疗的情况下进入糖尿病缓解。既往与永久性新生儿糖尿病相关的ABCC8/L225P变异的先证者在接受1年磺脲类治疗后进入7年长期缓解。7例具有KATP突变的糖尿病个体成功地用磺酰脲单药治疗; 4例复发6q24/TNDM患者用胰岛素、二甲双胍或联合治疗。 结论: 如果怀疑TNDM，应首先分析KATP基因，除了巨舌和/或脐疝患者。没有药物治疗的糖尿病缓解不应该排除遗传分析。早期使用磺酰脲类药物治疗可使与PNDM相关的KATP突变患者的糖尿病长期缓解。携带KATP/TNDM突变的成年患者对磺酰脲类单药治疗反应良好。
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.