BACKGROUND & AIMS: In almost all countries, the critical point for defining the nutritional status of a population is represented by the poor source of representative data of the whole population or of the main subgroups of the population. Also, in Italy, the sources of data on the nutritional status of biochemically evaluated macro- and micronutrients are scant in relation to specific groups of the population, mainly children and the elderly. In this short review, only the nutritional status for vitamins is considered. The existing limited data, however, indicate that clinical signs of severe deficiency are not observed in Italy and the incidence of vitamin malnutrition is moderate. This is probably due to the large availability and variety of food and to Italian eating habits which reflect the typical Mediterranean dietrich, for example, in cereals, fresh fruit and vegetables, and olive oil. However, there are particular conditions, linked to lifestyle, in which the risk of a mild or moderate vitamin malnutrition increases. These include a monotonous diet, drug interactions, smoking habits and alcohol consumption.

背景与目标： 在几乎所有国家中，定义人口营养状况的临界点都由整个人口或人口主要亚组的代表性数据来源不足所代表。此外，在意大利，与特定人群 (主要是儿童和老年人) 相比，生物化学评估的宏观和微量营养素的营养状况数据来源很少。在这篇简短的评论中，只考虑了维生素的营养状况。但是，现有的有限数据表明，在意大利未观察到严重缺乏的临床症状，并且维生素营养不良的发生率中等。这可能是由于食物的大量供应和种类以及意大利人的饮食习惯，这反映了典型的地中海dietrich，例如谷物，新鲜水果和蔬菜以及橄榄油。但是，在某些特定情况下，与生活方式有关，其中轻度或中度维生素营养不良的风险增加。这些包括单调的饮食，药物相互作用，吸烟习惯和饮酒。

BACKGROUND & AIMS: :Inborn errors of vitamin B(12) (cobalamin) metabolism are characterized by decreased production of active cobalamin cofactors and subsequent deficiencies in the activities of methionine synthase and methylmalonyl-CoA mutase. With the recent discovery of the cblJ defect in two patients with phenotypes mimicking the cblF defect, there are nine genes known to be involved in cobalamin metabolism. The new defect is caused by mutations in the ABCD4 gene, encoding an ABC transporter. At the moment, there is no clear distinction between the cblJ and cblF defects either clinically or biochemically, and both defects result in blocks in the transport of cobalamin from the lysosome to the cytoplasm. A patient was diagnosed with hyperhomocysteinemia and methylmalonic aciduria at the age of 8 years. Incorporations of both [(14)C]propionate and [(14)C]methyltetrahydrofolate in cultured fibroblasts were within reference ranges and thus too high to allow for complementation analysis. We observed decreased synthesis of both adenosylcobalamin and methylcobalamin and accumulation of unmetabolized cyanocobalamin. Exome sequencing was performed to identify causative mutation(s) and Sanger re-sequencing was performed to validate segregation of mutation in the family. By this approach, a homozygous mutation, c.423C>G, in the ABCD4 gene was identified. Here, we report the successful application of exome sequencing for diagnosis of a rare inborn error of vitamin B(12) metabolism in a patient whose unusual presentation precluded diagnosis using standard biochemical and genetic approaches. The patient represents only the third known patient with the cblJ disorder.

背景与目标： : 维生素b (12) (钴胺素) 代谢的先天性错误的特征是活性钴胺素辅因子的产生减少，随后蛋氨酸合酶和甲基丙二酰辅酶a变位酶的活性不足。随着最近在两名表型模仿cblF缺陷的患者中发现cblJ缺陷，已知有9个基因与钴胺素代谢有关。新的缺陷是由编码ABC转运蛋白的ABCD4基因突变引起的。目前，无论是在临床上还是在生化上，cblJ和cblF缺陷之间都没有明确的区别，这两个缺陷都会导致钴胺素从溶酶体到细胞质的转运受到阻碍。一名患者在8岁时被诊断出患有高同型半胱氨酸血症和甲基丙二酸尿症。培养的成纤维细胞中 [(14)C] 丙酸酯和 [(14)C] 甲基四氢叶酸的加入都在参考范围内，因此太高，无法进行互补分析。我们观察到腺苷钴胺和甲钴胺的合成减少以及未代谢的氰钴胺的积累。进行外显子组测序以鉴定致病突变 (s)，并进行了Sanger重新测序以验证家族中突变的分离。通过这种方法，在ABCD4基因中发现了一个纯合突变，c.423C>G。在这里，我们报告了外显子组测序在诊断罕见的先天性维生素b (12) 代谢错误中的成功应用，该患者的异常表现无法使用标准的生化和遗传学方法进行诊断。该患者仅代表第三位已知的cblJ疾病患者。

BACKGROUND & AIMS: :Recently, growing interest in vitamin D has emerged from findings that demonstrate a low vitamin D status in populations. Similarly, much interest has been shown in the role that anti-Müllerian hormone (AMH) plays in reproductive physiology. Considerable confusion as to whether vitamin D status is related to ovarian function can be found in the literature. Our retrospective study was performed from June 2014 to April 2015. Oocyte donors were recruited and stimulated under the antagonist protocol with gonadotrophin-releasing hormone (GnRH) agonist to trigger ovulation. In 851 stimulation cycles, we determined the association among serum total and bioavailable vitamin D levels, ovarian reserve and response to ovarian stimulation and the reproductive outcome in their recipients. We showed that vitamin D levels were unrelated to ovarian reserve or ovarian response after ovarian stimulation; in oocyte recipients, gestational outcome did not differ according to a donor's vitamin D serum status. No correlation was observed between serum AMH and vitamin D. Bioavailable vitamin D was not related to recipients' ongoing pregnancy rate. Highly prevalent vitamin D insufficiency neither impaired ovarian reserve nor response or oocyte quality in egg donors. No evidence was found for recommending the analysis of vitamin D status in oocyte donors.

背景与目标： : 最近，人们对维生素d的兴趣日益浓厚，这些发现表明人群中维生素d水平较低。同样，人们对抗苗勒激素 (AMH) 在生殖生理学中的作用也表现出了极大的兴趣。在文献中可以发现关于维生素d状态是否与卵巢功能有关的相当困惑。我们的回顾性研究是从2014年6月到2015年4月进行的。招募卵母细胞供体，并在拮抗剂方案下用促性腺激素释放激素 (GnRH) 激动剂刺激排卵。在851刺激周期中，我们确定了血清总维生素d和生物利用维生素d水平，卵巢储备和对卵巢刺激的反应以及接受者的生殖结果之间的关联。我们发现维生素d水平与卵巢储备或卵巢刺激后的卵巢反应无关; 在卵母细胞接受者中，根据供体的维生素d血清状态，妊娠结局没有差异。血清AMH与维生素d之间没有相关性。生物利用维生素d与接受者的持续怀孕率无关。非常普遍的维生素d不足不会损害卵子供体的卵巢储备，反应或卵母细胞质量。没有发现建议分析卵母细胞供体中维生素d状态的证据。

BACKGROUND & AIMS: :The aim of this work is to evaluate vitamins B antimutagenic effect against alkylatings methyl-N-nitro-N-nitrosoguanidine (MNNG), ethyl-N-nitro-N'- nitrosoguanidine (ENNG), frameshift mutagens 2-aminoanthracene (2AA) and 2-acetyl-amino-fluorene (2AF) and ROS-generating antibiotics norfloxacin (NOR) and nalidixic acid (NLX), using the in vitro Ames test. In vivo antimutagenesis studies were performed against urinary mutagens induced by NOR (70 mg/kg) or NLX (100 mg/kg) in CD1 mice. Vitamin B1 was antimutagenic against alkylatings MNNG (P<0.05) or ENNG (P<0.001). In fact as per the results observed during the current study, none of the vitamins reduced mutagenesis caused by frameshift mutagens. All of them reduced mutagenesis of NOR or NLX (P<0.001). In vivo studies showed that vitamins B1 and B6 (10 or 100 mg/kg) reduced urinary mutagens from NOR (P<0.001) or NLX (P<0.02) either free or β-glucoronidase-conjugates. None of the studied samples were toxic for the employed antimutagenic system. Vitamin B12 (4 mg/kg) reduced urinary mutagens of NOR or NLX (P<0.02). Vitamins B inhibited DNA mutations induced by ROS generated by NLX or NOR, both in vitro and in vivo. Vitamin B1is antimutagenic against mutations induced by the alkylating MNNG or ENNG. Based on the observations, employment of vitamins B in vivo can be a promising alternative to reduce genotoxic risk exposure to ROS.

背景与目标： : 这项工作的目的是评估维生素b对烷基甲基-N-硝基-N-亚硝基胍 (MNNG)，乙基-N-硝基-N'-亚硝基胍 (ENNG) 的抗诱变作用，使用体外Ames测试，移码诱变剂2-氨基蒽 (2AA) 和2-乙酰氨基芴 (2AF) 以及产生ROS的抗生素诺氟沙星 (NOR) 和萘啶酸 (NLX)。对在CD1小鼠中由NOR (70 mg/kg) 或NLX (100 mg/kg) 诱导的尿诱变剂进行体内抗诱变研究。维生素B1对烷基化物MNNG (P<0.05) 或ENNG (P<0.001) 具有抗诱变作用。实际上，根据当前研究中观察到的结果，没有一种维生素可以减少由移码诱变剂引起的诱变。它们均降低了NOR或NLX的诱变 (P<0.001)。体内研究表明，维生素B1和B6 (10或100 mg/kg) 减少了游离或 β-葡萄糖苷酶结合物的NOR (P<0.001) 或NLX (P<0.02) 的尿诱变剂。所研究的样品均未对所使用的抗诱变系统有毒。维生素B12 (4 mg/kg) 降低了NOR或NLX的尿诱变剂 (P<0.02)。维生素b在体外和体内均抑制由NLX或NOR产生的ROS诱导的DNA突变。维生素b1抗诱变抗烷基化MNNG或ENNG诱导的突变。根据观察结果，在体内使用维生素b可能是减少ROS的遗传毒性风险的有希望的替代方法。

BACKGROUND & AIMS: :Vitamin D hormone (1,25-dihydroxyvitamin D) is involved in innate immunity and induces host defense peptides in epithelial cells, suggesting its involvement in mucosal defense against infections. Chlamydia trachomatis is a major cause of bacterial sexually transmitted disease worldwide. We tested the hypothesis that the vitamin D endocrine system would attenuate chlamydial infection. Vitamin D receptor knock-out mice (VDR(-/-)) and wild-type mice (VDR(+/+)) were infected with 10(3) inclusion forming units of Chlamydia muridarum and cervical epithelial cells (HeLa cells) were infected with C. muridarum at multiplicity of infection 5:1 in the presence and absence of 1,25-dihydroxyvitamin D3. VDR(-/-) mice exhibited significantly higher bacterial loading than wild-type VDR(+/+) mice (P<0.01) and cleared the chlamydial infection in 39 days, compared with 18 days for VDR(+/+) mice. Monocytes and neutrophils were more numerous in the uterus and oviduct of VDR(-/-) mice than in VDR(+/+) mice (P<0.05) at d 45 after infection. Pre-treatment of HeLa cells with 10nM or 100nM 1,25-dihydroxyvitamin D3 decreased the infectivity of C. muridarum (P<0.001). Several differentially expressed protein spots were detected by proteomic analysis of chlamydial-infected HeLa cells pre-treated with 1,25-dihydroxyvitamin D3. Leukocyte elastase inhibitor (LEI), an anti-inflammatory protein, was up-regulated. Expression of LEI in the ovary and oviduct of infected VDR(+/+) mice was greater than that of infected VDR(-/-) mice. We conclude that the vitamin D endocrine system reduces the risk for prolonged chlamydial infections through regulation of several proteins and that LEI is involved in its anti-inflammatory activity.

背景与目标： : 维生素d激素 (1,25-二羟基维生素d) 参与先天免疫，并在上皮细胞中诱导宿主防御肽，表明其参与粘膜防御感染。沙眼衣原体是全球细菌性性传播疾病的主要原因。我们检验了维生素d内分泌系统会减轻衣原体感染的假设。维生素d受体敲除小鼠 (VDR(-/-)) 和野生型小鼠 (VDR (/)) 感染了10(3) 包涵体形成单位的衣原体和宫颈上皮细胞 (HeLa细胞) 感染多重性的C. muridarum 5:1在存在和不存在1的情况下，25-二羟基维生素d3。VDR(-/-) 小鼠表现出显著高于野生型VDR(+/+) 小鼠的细菌负荷 (P<0.01)，并且在39天内清除衣原体感染，而VDR(+/+) 小鼠为18天。在感染后第45天，VDR(-/-) 小鼠的子宫和输卵管中的单核细胞和中性粒细胞多于VDR (/+) 小鼠 (P<0.05)。用10nM或100nM 1,25-二羟基维生素D3预处理HeLa细胞会降低C. muridarum的感染性 (P<0.001)。通过用1,25-二羟基维生素d3预处理的衣原体感染的HeLa细胞的蛋白质组学分析，检测了几个差异表达的蛋白质斑点。抗炎蛋白白细胞弹性蛋白酶抑制剂 (LEI) 上调。感染的VDR (/) 小鼠的卵巢和输卵管中LEI的表达大于感染的VDR(-/-) 小鼠的表达。我们得出的结论是，维生素d内分泌系统通过调节多种蛋白质降低了长期衣原体感染的风险，并且LEI参与了其抗炎活性。

BACKGROUND & AIMS: Context:Vitamin D deficiency patients have an increased cardiovascular (CV) morbidity and mortality. Carotid intima-media thickness (IMT) and carotid plaques are markers of subclinical atherosclerosis and predictors of CV events. Objective:To perform a meta-analysis of studies evaluating the impact of Vitamin D deficiency on common carotid artery IMT (CCA-IMT) and on the prevalence of carotid plaques. Data Sources:Studies were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Results:Twenty-one studies (3,777 Vitamin D deficiency patients and 4,792 controls) with data on CCA-IMT and 6 studies (1,889 Vitamin D deficiency patients and 2,883 controls) on the prevalence of carotid plaques were included. Compared to controls, Vitamin D deficiency patients showed a significantly higher CCA-IMT (mean difference [MD]: 0.043 mm; 95%CI: 0.030, 0.056; P<0.001), and an increased prevalence of carotid plaques (Odds Ratio [OR]: 2.29, 95%CI: 1.03-5.11; P=0.043) with an attributable risk of 35.9%. When selecting studies specifically including patients with diabetes, the prevalence of carotid plaques in Vitamin D deficiency patients than in controls resulted higher (OR: 3.27; 95%CI: 1,62-6.62; P=0.001). A significant difference in CCA-IMT was confirmed when comparing patients with Vitamin D insufficiency to controls (MD: 0.011; 95%CI: 0.010-0.012, P<0.001). Sensitivity analyses substantially confirmed results and regression models showed that with the exception of LDL-cholesterol, HDL-cholesterol, triglycerides and the prevalence of hypercholesterolemia, all the other clinical and demographic co-variates significantly impacted on the difference in CCA-IMT between Vitamin D deficiency patients and controls. Conclusions:Both Vitamin D deficiency and Vitamin D insufficiency are associated with subclinical atherosclerosis, potentially suggesting an increased CV risk in these clinical settings.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Left atrial enlargement, a sensitive integrator of left ventricular diastolic function, is associated with increased cardiovascular morbidity and mortality. Vitamin D is linked to lower cardiovascular morbidity, possibly modifying cardiac structure and function; however, firm evidence is lacking. We assessed the effect of an activated vitamin D analog on left atrial volume index (LAVi) in a post hoc analysis of the PRIMO trial (clinicaltrials.gov: NCT00497146). METHODS AND RESULTS:One hundred ninety-six patients with chronic kidney disease (estimated glomerular filtration rate 15-60 mL/min per 1.73 m(2)), mild to moderate left ventricular hypertrophy, and preserved ejection fraction were randomly assigned to 2 μg of oral paricalcitol or matching placebo for 48 weeks. Two-dimensional echocardiography was obtained at baseline and at 24 and 48 weeks after initiation of therapy. Over the study period, there was a significant decrease in LAVi (-2.79 mL/m(2), 95% CI -4.00 to -1.59 mL/m(2)) in the paricalcitol group compared with the placebo group (-0.70 mL/m(2) [95% CI -1.93 to 0.53 mL/m(2)], P = .002). Paricalcitol also attenuated the rise in levels of brain natriuretic peptide (10.8% in paricalcitol vs 21.3% in placebo, P = .02). For the entire population, the change in brain natriuretic peptide correlated with change in LAVi (r = 0.17, P = .03). CONCLUSIONS:Forty-eight weeks of therapy with an active vitamin D analog reduces LAVi and attenuates the rise of BNP. In a population where only few therapies alter cardiovascular related morbidity and mortality, these post hoc results warrant further confirmation.

背景与目标：

BACKGROUND & AIMS: :Vitamin D and its analogues exhibit potent antitumor effects in many tissues, including the pancreas. Normal and malignant pancreatic tissues were recently shown to express high levels of vitamin D 1-alpha-hydroxylase, which converts circulating 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D. We examined associations between dietary intake of vitamin D, calcium, and retinol and subsequent risk for pancreatic cancer. We conducted prospective studies in cohorts of 46,771 men ages 40 to 75 years as of 1986 (the Health Professionals Follow-up Study), and 75,427 women ages 38 to 65 years as of 1984 (the Nurses' Health Study), documenting incident pancreatic cancer through the year 2000. Diet was ascertained by semiquantitative food-frequency questionnaire. We identified 365 incident cases of pancreatic cancer over 16 years of follow-up. Compared with participants in the lowest category of total vitamin D intake (<150 IU/d), pooled multivariate relative risks for pancreatic cancer were 0.78 [95% confidence interval (95% CI), 0.59-1.01] for 150 to 299 IU/d, 0.57 (95% CI, 0.40-0.83) for 300 to 449 IU/d, 0.56 (95% CI, 0.36-0.87) for 450 to 599 IU/d, and 0.59 (95% CI, 0.40-0.88) for >/=600 IU/d (P(trend) = 0.01). These associations may be stronger in men than women. After adjusting for vitamin D intake, calcium and retinol intakes were not associated with pancreatic cancer risk. In two U.S. cohorts, higher intakes of vitamin D were associated with lower risks for pancreatic cancer. Our results point to a potential role for vitamin D in the pathogenesis and prevention of pancreatic cancer.

背景与目标： : 维生素d及其类似物在包括胰腺在内的许多组织中表现出有效的抗肿瘤作用。最近显示正常和恶性胰腺组织表达高水平的维生素d 1-α-羟化酶，可将循环中的25-羟基维生素d转化为活性的1,25-二羟基维生素d。我们研究了饮食中维生素d，钙和视黄醇的摄入量与胰腺癌后续风险之间的关联。我们对46,771名年龄在40 ~ 75岁的男性作为1986年 (健康专业人员随访研究) 和75,427名年龄在38 ~ 65岁的女性作为1984年 (护士健康研究) 进行了前瞻性研究，记录了通过2000年发生的胰腺癌。通过半定量食物频率问卷确定饮食。在16年的随访中，我们确定了365例胰腺癌事件。与维生素d总摄入量最低类别 (<150 IU/D) 的参与者相比，胰腺癌的合并多变量相对风险被0.78 [95% 置信区间 (95% CI)，0.59-1.01] 150至299 IU/d，0.57 (95% CI，0.40-0.83) 300至449 IU/d，0.56 (95% CI，0.36-0.87) 450至599 IU/d，0.59 (95% CI，0.40-0.88)>/= 600 IU/d (P (趋势) = 0.01)。这些联想在男性中可能比女性更强。调整维生素d摄入量后，钙和视黄醇的摄入量与胰腺癌风险无关。在两个美国队列中，较高的维生素d摄入量与较低的胰腺癌风险相关。我们的结果指出维生素d在胰腺癌的发病机理和预防中的潜在作用。

BACKGROUND & AIMS: BACKGROUND:Type 1 diabetes (T1D) is an autoimmune disease which is characterised by the destruction of insulin-producing beta cells in human pancreas leading consequently to a hyperglycaemic metabolism. Recent studies have shown that low cholecalciferol (25(OH)D3) concentrations may contribute to the development of T1D. The 25(OH)D3 status depends mostly on human skin production influenced by exposure to UVB radiation. Our intention was to examine whether there was a change in UVB radiation in the past years and if this has an impact on patients' vitamin D status. METHODS:We analysed the 25(OH)D3 concentration of blood samples from 287 T1D patients in the years 2004-2007 at the University Hospital Frankfurt. Moreover, daily UVB irradiation data of this time were received. Wilcoxon-Mann-Whitney test and Spearman correlation test were used for statistical analyses. RESULTS:We observe a strong correlation between UVB irradiation and the 25(OH)D3 concentration of German T1D patients (correlation coefficient=rho=0.56, p=7×10(-3)). Moreover, 25(OH)D3 blood levels obtained in summer (Apr-Oct) were significantly higher than in the winter season (p=8×10(-3)). In the years 2004-2007 there was a significant decline of UVB radiation in the summers (rho=-0.21, p<10(-6)) but no change was found in (rho=-0.07, p=0.12). This corresponds to a significant decrease of 25(OH)D3 levels in T1D patients over the summers (rho=-0.24, p=2×10(-3)) but not in winters (rho=-0.03, p=0.73). CONCLUSION:Our results reveal a significant correlation of UVB irradiation and the vitamin D concentration of German T1D patients. A decrease of UVB irradiation over the summers 2004-2007 is accompanied by a decline of 25(OH)D3 levels observed in those summer months which may indicate a local time trend requiring further investigation into the environmental factors of vitamin D deficiency. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

背景与目标：

BACKGROUND & AIMS: :Vitamin D deficiency is associated with osteoporosis and is thought to increase the risk of cancer and CVD. Despite these numerous potential health effects, data on vitamin D status at the population level and within key subgroups are limited. The aims of the present study were to examine patterns of 25-hydroxyvitamin D (25(OH)D) levels worldwide and to assess differences by age, sex and region. In a systematic literature review using the Medline and EMBASE databases, we identified 195 studies conducted in forty-four countries involving more than 168 000 participants. Mean population-level 25(OH)D values varied considerably across the studies (range 4·9-136·2 nmol/l), with 37·3 % of the studies reporting mean values below 50 nmol/l. The highest 25(OH)D values were observed in North America. Although age-related differences were observed in the Asia/Pacific and Middle East/Africa regions, they were not observed elsewhere and sex-related differences were not observed in any region. Substantial heterogeneity between the studies precluded drawing conclusions on overall vitamin D status at the population level. Exploratory analyses, however, suggested that newborns and institutionalised elderly from several regions worldwide appeared to be at a generally higher risk of exhibiting lower 25(OH)D values. Substantial details on worldwide patterns of vitamin D status at the population level and within key subgroups are needed to inform public health policy development to reduce risk for potential health consequences of an inadequate vitamin D status.

背景与目标： 维生素d缺乏与骨质疏松症有关，被认为会增加患癌症和CVD的风险。尽管有这些潜在的健康影响，但人口水平和关键亚组中维生素d状况的数据有限。本研究的目的是检查世界范围内25-羟基维生素d (25(OH)D) 水平的模式，并评估年龄，性别和地区的差异。在使用Medline和EMBASE数据库的系统文献综述中，我们确定了在44个国家进行的195项研究，涉及168 000多名参与者。在整个研究中，平均人口水平25(OH) d值差异很大 (范围为4·9-136·2 nmol/l)，37·3% 的研究报告平均值低于50 nmol/l。在北美观察到最高的25(OH) d值。尽管在亚洲/太平洋和中东/非洲地区观察到与年龄相关的差异，在其他地方没有观察到它们，在任何地区也没有观察到性别相关的差异。研究之间的实质性异质性排除了对人口水平总体维生素d状况的结论。然而，探索性分析，建议来自世界各地的几个地区的新生儿和住院老人似乎普遍处于较低的25(OH) d值的较高风险中。需要在人口水平和关键亚组中详细了解全球范围内的维生素d状况，以告知公共卫生政策制定以降低潜在健康后果的风险维生素d水平不足。

BACKGROUND & AIMS: :Vitamin K was discovered fortuitously in 1929 as part of experiments on sterol metabolism and was immediately associated with blood coagulation. In the decade that followed, the principal K vitamers, phylloquinone and the menaquinones, were isolated and fully characterized. In the early 1940s, the first vitamin K antagonists were discovered and crystallized with one of its derivatives, warfarin, still being widely used in today's clinical setting. However, major progress in our understanding of the mechanisms of action of vitamin K came in the 1970s with the discovery of γ-carboxyglutamic acid (Gla), a new amino acid common to all vitamin K proteins. This discovery not only provided the basis to understanding earlier findings about prothrombin but later led to the discovery of vitamin K-dependent proteins (VKDPs) not involved in hemostasis. The 1970s also saw an important breakthrough with respect to our understanding of the vitamin K cycle and marked the discovery of the first bone VKDP, osteocalcin. Important studies relating to the role of vitamin K in sphingolipid synthesis were also underway at that time and would pave the way to further work 15 years later. The decades that followed saw the discovery of additional VKDPs showing wide tissue distribution and functional scope, the latest members having been identified in 2008. The 1990s and 2000s were also marked by important epidemiological and intervention studies that focused on the translational impact of recent vitamin K discoveries, notably with respect to bone and cardiovascular health. This short review presents an overview of the history of vitamin K and of its recent developments.

背景与目标： : 维生素k在甾醇代谢实验中被发现1929年，并立即与血液凝固有关。在随后的十年中，分离并充分表征了主要的K维生素，叶绿醌和menaquinones。在20世纪40年代初中，发现了第一批维生素k拮抗剂，并以其衍生物之一华法林结晶，在当今的临床环境中仍被广泛使用。然而，20世纪70年代发现了 γ-羧基谷氨酸 (Gla)，这是所有维生素k蛋白共有的新氨基酸，因此我们对维生素k作用机制的理解取得了重大进展。这一发现不仅为理解早期关于凝血酶原的发现提供了基础，而且后来导致发现了不参与止血的维生素k依赖性蛋白 (VKDPs)。该20世纪70年代在我们对维生素k循环的理解方面也取得了重要突破，并标志着第一个骨VKDP (骨钙素) 的发现。有关维生素k在鞘脂合成中的作用的重要研究也在当时进行，并将为15年后的进一步工作铺平道路。在随后的几十年中，发现了其他vkdp，显示出广泛的组织分布和功能范围，2008年发现了最新的成员。20世纪90年代和21世纪00年代还以重要的流行病学和干预研究为标志，这些研究侧重于最近发现的维生素k的转化影响，尤其是在骨骼和心血管健康方面。这篇简短的评论概述了维生素k的历史及其最新发展。

BACKGROUND & AIMS: :The purpose of this study was to clarify the effects of nutrients on the gonadal development of male rats kept under constant darkness as a model of disturbed daily rhythm. The present study examined protein and vitamins, and their interactions. This study was based on three-way ANOVA; the three factors were lighting conditions, dietary protein and dietary vitamins, respectively. The levels of dietary protein were low or normal: 9% casein or 20% casein. The levels of dietary vitamins were low, normal or high: 1/3.3 of normal (AIN-93G diet) content, normal content, or three times the normal content, respectively. Other compositions were the same as those of the AIN-93G diet, and six kinds of experimental diet were prepared. Four-week-old rats (Fischer 344 strain) were kept under constant darkness or normal lighting (12-h light/dark cycle) for 4 wk. After 4 wk, the gonadal weights and serum testosterone content were evaluated. In the constant darkness groups (D-groups), the low-protein diet induced reduction of gonadal organ weights and serum testosterone concentrations. This reduction of gonadal organ weights was exacerbated by progressively higher levels of dietary vitamins. In the case of a normal-protein diet, the depression of gonadal development was not accelerated by high-vitamin intake. In the normal lighting groups (N-groups), the low-protein and high-vitamin diet slightly depressed gonadal development. These results suggest that the metabolism of protein and vitamins is different in rats being kept under constant darkness, and that excess dietary vitamins have an adverse effect on gonadal development in rats fed a low-protein diet.

背景与目标： : 这项研究的目的是阐明营养物质对持续处于黑暗状态下的雄性大鼠性腺发育的影响，以此作为每日节律紊乱的模型。本研究检查了蛋白质和维生素及其相互作用。本研究基于三次方差分析; 这三个因素分别是光照条件、膳食蛋白质和膳食维生素。膳食蛋白质水平低或正常: 9% 酪蛋白或20% 酪蛋白。饮食中的维生素水平低，正常或高: 正常 (AIN-93G饮食) 含量的1/3.3，正常含量或正常含量的3倍。其他组成与AIN-93G饮食相同，并准备了六种实验饮食。将4周龄的大鼠 (Fischer 344品系) 保持在恒定的黑暗或正常照明下 (12小时的光/暗周期) 4周。4周后，评估性腺重量和血清睾丸激素含量。在恒定的黑暗组 (D组) 中，低蛋白饮食导致性腺器官重量和血清睾丸激素浓度降低。饮食中维生素的含量逐渐增加，加剧了性腺器官重量的减少。在正常蛋白质饮食的情况下，高维生素摄入量不会加速性腺发育的抑制。在正常照明组 (N组) 中，低蛋白和高维生素饮食会稍微抑制性腺发育。这些结果表明，在持续黑暗的情况下，大鼠的蛋白质和维生素的代谢是不同的，并且过量的饮食维生素对喂养低蛋白饮食的大鼠的性腺发育有不利影响。

BACKGROUND & AIMS: OBJECTIVE:To review recent evidence that suggests vitamin B12 is associated with risk reduction for some chronic diseases and birth defects. QUALITY OF EVIDENCE:A MEDLINE search from 1999 to 2007 was performed using the key word vitamin B12. The most relevant articles (129) dealt with cardiovascular disease, cancer, mental health, and birth outcomes;most studies presented level II evidence. MAIN MESSAGE:Vitamin B12 might confer health benefits; however, such benefits are difficult to ascertain because of the complementary functions of vitamin B12 and folic acid. Vitamin B12 might lower high homocysteine levels below a threshold level achieved by folic acid alone. Furthermore, the interactions between the nutritional environment and genotype might have an important influence on vitamin B12, chronic disease risk, and risk of neural tube defects. CONCLUSION:Vitamin B12 might help protect against chronic disease and neural tube defects, but more research, particularly in the area of nutritional genomics, is needed to determine how vitamin B12 might augment the benefits of folic acid. Some consideration should be given to the potential value of fortifying foods with vitamin B12 in addition to the current mandatory folic acid fortification of grains.

背景与目标：

BACKGROUND & AIMS: :The purpose of this review is to summarize the peer-reviewed literature in relation to sunlight exposure assessment and the validity of using sunlight exposure questionnaires to quantify vitamin D status. There is greater variability in personal ultraviolet (UV) light exposure as the result of personal behavior than as the result of ambient UV light exposure. Although statistically significant, the correlation coefficients for the relation between personal report of sun exposure and ambient UV light measured by dosimetry (assessment of radiation dose) are relatively low. Moreover, the few studies to assess the relation between sunlight measures and serum 25-hydroxyvitamin D show low correlations. These low correlations may not be surprising given that personal factors like melanin content in skin and age also influence cutaneous synthesis of vitamin D. In summary, sunlight exposure questionnaires currently provide imprecise estimates of vitamin D status. Research should be directed to develop more objective, nonintrusive, and economical measures of sunlight exposure to quantify personal vitamin D status.

背景与目标： : 本综述的目的是总结与阳光暴露评估有关的同行评审文献，以及使用阳光暴露问卷量化维生素d状态的有效性。由于个人行为的结果，个人紫外线 (UV) 光暴露比环境紫外线暴露的结果具有更大的可变性。尽管具有统计学意义，但通过剂量测定法 (辐射剂量评估) 测量的个人日晒报告与环境紫外线之间关系的相关系数相对较低。此外，评估阳光测量与血清25-羟基维生素d之间关系的研究很少，但相关性较低。鉴于皮肤和年龄中的黑色素含量等个人因素也会影响皮肤维生素d的合成，因此这些低相关性可能不足为奇。总之，阳光暴露问卷目前提供了不精确的维生素d状况估计。应该进行研究，以开发更客观，非侵入性和经济的日光照射措施，以量化个人维生素d的状况。

BACKGROUND & AIMS: BACKGROUND:Atherosclerotic cardiovascular disease is the most common cause of death among hemodialysis patients; it has been attributed to increased oxidative stress, dyslipidemia, malnutrition, and chronic inflammation. Activation of neutrophils is a well-recognized feature in dialysis patients, and superoxide-anion production by neutrophil NADPH oxidase may contribute significantly to oxidative stress. OBJECTIVE:The aim of the study was to compare the effects of dietary supplementation with concentrated red grape juice (RGJ), a source of polyphenols, and vitamin E on neutrophil NADPH oxidase activity and other cardiovascular risk factors in hemodialysis patients. DESIGN:Thirty-two patients undergoing hemodialysis were recruited and randomly assigned to groups to receive dietary supplementation with RGJ, vitamin E, or both or a control condition without supplementation or placebo. Blood was obtained at baseline and on days 7 and 14 of treatment. RESULTS:RGJ consumption but not vitamin E consumption reduced plasma concentrations of total cholesterol and apolipoprotein B and increased those of HDL cholesterol. Both RGJ and vitamin E reduced plasma concentrations of oxidized LDL and ex vivo neutrophil NADPH oxidase activity. These effects were intensified when the supplements were used in combination; in that case, reductions in the inflammatory biomarkers intercellular adhesion molecule 1 and monocyte chemoattractant protein 1 also were observed. CONCLUSIONS:Regular ingestion of concentrated RGJ by hemodialysis patients reduces neutrophil NADPH-oxidase activity and plasma concentrations of oxidized LDL and inflammatory biomarkers to a greater extent than does that of vitamin E. This effect of RGJ consumption may favor a reduction in cardiovascular risk.

背景与目标：