Vitamin D insufficiency among Danish pregnant women-Prevalence and association with adverse obstetric outcomes and placental vitamin D metabolism.
- 作者列表："Vestergaard AL","Justesen S","Volqvartz T","Aagaard SK","Andreasen MF","Lesnikova I","Uldbjerg N","Larsen A","Bor P
INTRODUCTION:In pregnancy, vitamin D deficiency is associated with increased risk of fetal growth restriction and preeclampsia. The underlying mechanisms are not known, but placental dysfunction is believed to play a role. In a Danish population, where health authorities recommend a 10 µg/day vitamin D supplement during pregnancy, we explored current use of vitamin D supplements and vitamin D status. In term placentas, alterations in vitamin D metabolism and placental growth, evaluated by the key placental growth factor pregnancy-associated plasma protein-A (PAPP-A), and their relation to vitamin D insufficiency were investigated. MATERIAL AND METHODS:We included 225 randomly selected pregnant women attending a nuchal translucency scan at gestational weeks 11-14. Information on use of vitamin D supplements and body mass index (BMI) at inclusion was obtained using self-reported questionnaires. Plasma 25-hydroxyvitamin D was measured at inclusion and correlated with pregnancy outcomes and placental biology, as judged by expression of PAPP-A and enzymes involved in vitamin D metabolism (CYP24A1, CYP27B1) in term placentas. RESULTS:Vitamin D supplements were used by 92% of the women, but 42% were vitamin D insufficient (plasma 25-hydroxyvitamin D <75 nmol/L). Eleven women with singleton pregnancies developed fetal growth restriction or preeclampsia. In this small subset, first-trimester mean plasma 25-hydroxyvitamin D was lower in women who developed fetal growth restriction (43 ± 33nmol/L; n = 3; P = .006) and there was a tendency towards lower plasma 25-hydroxyvitamin D among women who developed preeclampsia (65 ± 19 nmol/L; n = 8; P = .08) in third trimester compared with uncomplicated pregnancies (79 ± 22 nmol/L; n = 187). In term placentas, PAPP-A expression was lower among participants with first-trimester vitamin D insufficiency (P = .009; n = 30) but no correlation was found between plasma 25-hydroxyvitamin D and mRNA expression of CYP24A1 (P = .67) and CYP27B1 (P = .34). BMI was negatively correlated with plasma 25-hydroxyvitamin D (P = .03) and positively correlated with placental mRNA expression of CYP24A1 (P = .003; n = 30). CONCLUSIONS:Despite high compliance with official guidelines regarding vitamin D supplements, vitamin D insufficiency was frequent and the findings indicate that vitamin D insufficiency may affect placental growth. High BMI was associated with vitamin D insufficiency and increased placental vitamin D turnover, but further investigations are needed.
介绍: 在怀孕期间，维生素d缺乏与胎儿生长受限和先兆子痫的风险增加有关。潜在的机制尚不清楚，但胎盘功能障碍被认为发挥了作用。在丹麦人群中，卫生当局建议在怀孕期间补充10 µ g/天的维生素d，我们探讨了目前维生素d补充剂的使用情况和维生素d状况。在术语胎盘中，研究了关键胎盘生长因子妊娠相关血浆蛋白-A (papp-a) 评估的维生素d代谢和胎盘生长的改变，以及它们与维生素d不足的关系。 材料和方法: 我们纳入了225名随机选择的孕妇，在妊娠11-14周进行颈项透明层扫描。在纳入时使用维生素d补充剂和体重指数 (BMI) 的信息通过自我报告的问卷获得。在纳入时测量血浆25-羟基维生素d，并与妊娠结局和胎盘生物学相关，如通过papp-a和参与维生素d代谢的酶 (CYP24A1，CYP27B1) 在足月胎盘中的表达来判断。 结果: 92% 的女性使用了维生素d补充剂，但42% 的女性维生素d不足 (血浆25-羟基维生素d <75 nmol/L)。11例单胎妊娠妇女出现胎儿生长受限或先兆子痫。在这个小的亚组中，发生胎儿生长受限的女性孕早期平均血浆25-羟基维生素d较低 (43 ± 33nmol/L; n = 3; P = .006) 在发生先兆子痫的妇女中，血浆25-羟维生素d水平有降低的趋势 (65 ± 19 nmol/L; n = 8;P = .08)，与无并发症妊娠相比 (79 ± 22 nmol/L; n = 187)。在足月胎盘中，孕早期维生素d不足的参与者中papp-a表达较低 (P = .009; n = 30)，但血浆25-羟基维生素d与CYP24A1 (P = .67) 和CYP27B1 (P = .34) 的mRNA表达之间没有相关性。BMI与血浆25-羟维生素d呈负相关 (P = .03)，与胎盘CYP24A1 mRNA表达呈正相关 (P = .003; n = 30)。 结论: 尽管对有关维生素d补充剂的官方指南有很高的依从性，但维生素d不足是常见的，研究结果表明维生素d不足可能会影响胎盘生长。高BMI与维生素d不足和胎盘维生素d转换增加相关，但需要进一步调查。
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.