Life-threatening complications of vitamin D intoxication due to over-the-counter supplements

Introduction. Ninety percent of hypercalcemic cases are caused by primary hyperparathyroidism or malignancy. Less frequent causes are granulomatous diseases, drug-induced diseases, and intoxications. Case report. We present two women with life-threatening hypercalcemia due to the intake of vitamin D-concentrated supplements, which turned out to be 100–1,000 times higher than stated on the label of over-the-counter dietary supplements. Laboratory analysis revealed ionized calcium levels of 4.00 (16.00) and 4.56 mmol/L (18.24 mg/dL) with vitamin D₂₅ concentrations of 1,372 and 644 nmol/L, respectively. Apart from a patient with general symptoms of hypercalcemia, a case of refractory status epilepticus after correction of serum calcium levels, and in need of prolonged ICU treatment, is described. Conclusion. Initial drug-taking history in the presented cases did not reveal the use of over-the-counter supplements, which underlines the importance of a thorough evaluation of (non-)prescribed medication. Moreover, these supplements may contain higher levels of vitamin D than the label states. As a result, hypercalcemia may be an underlying cause for life-threatening complications, including a well-documented refractory status epilepticus.     

维生素D对老年缺血性脑卒中患者抗血小板药物反应性的影响

目的探讨老年缺血性脑卒中患者维生素D对阿司匹林和氯吡格雷联合治疗后血小板反应性的影响。方法选取2017年6月至2018年8月北京博爱医院接受阿司匹林和氯吡格雷联合治疗的老年缺血性脑卒中患者共190例,用药1~2周期间采集静脉血进行血小板聚集率、25-羟维生素D[25(OH)D]及临床生化指标检查,按照25(OH)D四分位数分为:Q1组(≤7.18μg/L)50例,Q2组(>7.18~≤9.39μg/L)50例,Q3组(>9.39~≤13.74μg/L)50例,Q4组(>13.74μg/L)40例。为了评估骨化三醇对血小板聚集的影响,健康组(15名)和氯吡格雷抵抗组(15例)的富血小板血浆(platelet rich plasma,PRP)均用骨化三醇(10 nmol/L)和生理盐水分别处理(37°C预处理5 min),比较两种处理方式下ADP诱导的最大血小板聚集率差异。结果维生素D四分位数各组间(升次)ADP诱导的最大血小板聚集率[(49.36±23.34)%,(48.80±20.90)%,(37.02±18.24)%,(36.02±14.46)%,F=3.426,P=0.018)、氯吡格雷抵抗/敏感比例比较差异均有统计学意义(30/20,24/26,15/35,10/30,χ^2=15.119,P=0.002),且随着维生素D浓度的升高,二者均呈依次下降趋势。Logistic回归分析显示,血清25(OH)D是老年缺血性脑卒中患者氯吡格雷抵抗的抑制因素(Q4与Q1,OR=0.699,95%CI 0.582~0.838,P<0.001;Q3与Q1,OR=0.848,95%CI 0.755~0.953,P=0.006)。在体外实验中,与生理盐水比较,骨化三醇预处理后,健康组与氯吡格雷抵抗组的血小板聚集率均有下降,差异均有统计学意义[健康组:(69.8±12.7)%与(58.6±11.5)%,t=12.13,P<0.001;抵抗组:(65.5±8.3)%与(56.3±7.6)%,t=11.48,P<0.001]。结论维生素D降低了抗血小板药物治疗后的高残留血小板反应性,需进一步研究证实补充维生素D是否会改善氯吡格雷疗效。     

Parathyroid hormone-related protein, parathyroid hormone, and vitamin D in hypercalcemia of malignancy

The pathogenesis of cancer-associated hypercalcemia is not yet completely understood. In the majority of cancer patients, hypercalcemia appears to be a consequence of the tumor production of parathyroid hormone (PTH)-related protein (PTHrP). However, patients with humoral hypercalcemia of malignancy, in contrast to those with primary hyperparathyroidism, have an uncoupled bone turnover, and they usually have low circulating levels of 1,25(OH)₂D₃. We performed a case-control study to assess the relationship of plasma PTHrP, PTH and 1,25(OH)₂D₃ with hypercalcemia in cancer patients with a variety of tumors. Sixty of these patients had hypercalcemia, and 45 were normocalcemic. We measured PTHrP and PTH by immunoradiometric assay (Nichols), and 1,25(OH)₂D₃ by radioreceptor assay (Nichols), in plasma in both groups of cancer patients. Using a logistic regression analysis, we found that the higher PTHrP in plasma, the higher association with hypercalcemia occurred in these patients. In addition, the decreased plasma levels of PTH and 1,25(OH)₂D₃ in the majority of cancer patients were found to be significantly associated with hypercalcemia. Our results indicate that the combined determination of PTH, PTHrP and 1,25(OH)₂D₃ in plasma represents a more comprehensive approach to the investigation of hypercalcemia in cancer patients. Our data also support the role of PTHrP as a humoral factor responsible for hypercalcemia in these patients.     

Structure-function relationships of vitamin D including ligand recognition by the vitamin D receptor

First, the general structure and function of nuclear receptors (NRs) are described briefly to help our understanding of the mechanism of action of vitamin D mediated by the vitamin D receptor (VDR), a member of the NRs. Then we discuss the structure-function relationship (SFR) of vitamin D on the basis of ligand structures and the interaction of the ligand with the VDR. The SFR of vitamin D side chain analogs is discussed extensively in terms of our active space group concept, which was derived from conformational analyses of the side chains of vitamin D analogs and from studies with conformationally restricted 22-methyl-1,25-(OH)(2)D(3) isomers. The mobile area of the side chain of vitamin D can be grouped into five regions (E, G, EA, EG, and F), and the SFR has been analyzed in terms of these spatial regions. The SFR of ligand/VDR interaction is discussed on the basis of the crystal structure of VDR-LBD(delta 165-215), docking of various vitamin D ligands into the ligand binding pocket (LBP) of the VDR, and functional analysis of amino acids lining the LBP. Finally, we discuss total SFR, combining the results of the two approaches, and future aspects of structure-based design of vitamin D analogs.     

血清维生素D降低的脊柱内固定术后肺部感染患者的病原菌分布与耐药性分析

目的:探讨血清维生素D水平对脊柱内固定手术患者肺部感染的影响及感染病原菌分布及药物敏感性.方法:选取2017年4月～2019年4月于我院接受治疗的266例脊柱内固定手术患者为研究对象,按照术后是否发生肺部感染分为感染组(n=52)和未感染组(n=214).采用高效液相色谱串联质谱仪检测患者总维生素D、维生素D2、维生素...     

医源性失误致后路腰椎融合固定疗效不佳原因分析

目的 分析后路腰椎融合固定疗效不佳的原因.方法 5a期间手术727例,对出现疗效不佳39例进行回顾性分析.结果 (1)手术失败17例:融合器退出8例、退钉椎体再滑脱2例、融合节段不合理4例、游离椎间盘未取1例、神经根损伤2例.(2)漏诊漏治12例:腰椎不稳和椎管狭窄6例、椎体压缩骨折3例、极外侧椎间盘突出2例、肝癌椎体转移1例.(3)误诊误治10例:股骨头缺血性坏死6例、盆腔肿瘤1例、直肠癌1例、梨状肌综合征2例误诊为腰椎间盘突出症并手术.结论 医源性失误导致治疗失败是术后疗效不佳的主要原因.     

The influence of maternal vitamin D supplementation on infant vitamin D status: A systematic review and meta-analyses

BackgroundInconsistencies exist with regard to effect of maternal vitamin D supplementation on infant vitamin D status. The inconsistencies could be attributed to numerous factors, such as duration of intervention and dosage, among others. In this work, we conducted a systematic review and meta-analysis to determine the influence of maternal vitamin D supplementation on infant vitamin D status.MethodsA comprehensive systematic search was performed in Scopus, EMBASE, Web of Science, and PubMed/MEDLINE, by investigators, from database inception until November 2019, without using any restrictions. Weighted mean difference (WMD) with the 95 % CI was used for assessing the effects of maternal vitamin D supplementation on 25(OH) D levels in infants.ResultsOverall results from 14 studies revealed a non-significant effect of maternal vitamin D administration on the level of 25(OH) D in breastfeeding infants (WMD: -0.464 ng/mL, 95 % CI: -6.68 to 5.75, p = 0.884, I² = 98 %). Subgroup analyses demonstrated that vitamin D supplementation dosage ≥2000 IU/day (WMD: 9 ng/mL, 95 % CI: 8.19, 9.82, I² = 99 %) and intervention duration ≥20 weeks (WMD: 16.20 ng/mL, 95 % CI: 14.89, 17.50, I² = 99 %) significantly increased 25(OH) D.ConclusionsThe main results indicate a non-significant increase in infant vitamin D following maternal vitamin D supplementation. Additionally, vitamin D supplementation dosage ≥2000 IU/day and intervention duration ≥20 weeks significantly increased infant 25(OH) D.     

维生素D中毒肾钙质沉着的超声表现

目的探讨维生素D中毒肾钙质沉着的超声表现。方法对12例维生素D中毒肾钙质沉着患者临床症状消失后肾脏超声表现进行总结分析。结果维生素D中毒肾钙质沉着超声表现为锥体边缘小灶状回声增强、锥体边缘环状回声增强及整个锥体回声增强。结论维生素D中毒肾钙质沉着通常超声表现为3种影像，且是不可逆的超声表现。     

维生素D及其受体在强直性脊柱炎患者中的表达及其临床意义

目的：研究As患者PBMC维生素D受体（VDR）mRNA的表达及血清25-羟维生素D,和1,25-二羟维生素D3的水平,探讨其与AS疾病活动性（BASDAI、CRP、ESR）的相关性。方法：选取26例AS患者（As组）和年龄、性别与之相匹配的13名健康志愿者（健康对照组）。采用SYBRGreenI实时荧光定量PCR检测两组受检者PBMC的VDRmRNA表达水平,应用ELISA法检测两组受检者血清25-羟维生素D3和1,25-二羟维生素D3水平,分析VDRmRNA表达水平、血清25-羟维生素D3和1,25-二羟维生素D3水平与临床相关指标（BASDAI、CRP、ESR）的关系。结果：As患者PBMC的VDRmRNA表达水平明显高于健康对照组（P〈0．01）,VDRmRNA表达水平与临床相关指标（BASDAI、CRP、ESR）无关（P〉0．05）。AS患者血清25．羟维生素D3、1,25-二羟维生素D3水平分别为（5．3±2．6）μg／L、（12．8±6．0）ng／L,明显低于健康对照组（14．7±3．5）μg/L、（32．6±18．5）ng／L（P均〈0．01）。AS患者血清1,25-二羟维生素D3的水平与BASDAI（r=-0．481,P〈0．05）、ESR（r=-0．535,P〈0．01）、CRP（r=-0．674,P〈0．01）均呈负相关。血清25-羟维生素D,水平与BASDAI、CRP、ESR无关（P〉0．05）。结论：As患者VDRmRNA表达水平升高,但与As的疾病活动无关。As患者血清1,25-二羟维生素D3水平下降,与疾病活动呈负相关,可作为AS疾病活动的指标之一。AS患者PBMC的VDR活化可能与1,25-二羟维生素D,的作用无关。     

妊娠合并重型肝炎医源性心力衰竭18例分析

目的探讨妊娠合并重型肝炎出现心力衰竭的特点、原因和预防。方法回顾分析18例出现心力衰竭的妊娠合并重型肝炎病例，观察其临床表现、诊治过程，就24h出入量、感染、贫血、水电解质酸碱平衡与无心衰组进行比较，统计方法采用卡方检验和t检验。结果妊娠合并重型肝炎心衰发生率45％（18／40）；所有患者入量均明显多于出量，与无心衰组对比差异有统计学意义，感染以及血红蛋白、血钠、血钾、血钙、血镁、碳酸氢根方面差异无统计学意义；所有患者经常规强心、利尿、扩血管处理效果欠佳，心力衰竭难以纠正。结论妊娠合并重型肝炎易发生心力衰竭，与出入量不平衡有关，这种心力衰竭常规处理效果欠佳，严格控制补液量和速度有利于减少心力衰竭的发生。     

Transport of vitamin D sterols in human plasma: effect of excess vitamin D, 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D

Abstract. Vitamin D and its more active metabolites, 25 hydroxyvitamin D (25-OH-D) and 1,25-dihydroxy-vitamin D (1,25-(OH)₂-D), are transported in human plasma on a specific binding protein (DBP), which has been shown to have an α-globulin electrophoretic mobility. Since the concentration of DBP in normal human plasma is approximately 5 μmol/l, whereas that of all the vitamin D metabolites is less than 0·2 μmol/l, DBP is less than 3% saturated under physiological conditions. We have studied the transport of the above-mentioned metabolites in human plasma in vitro at normal and saturating concentrations. Human plasma was incubated with increasing amounts of vitamin D metabolites together with their radiolabelled tracers. Ultracentrifugation was used to isolate plasma lipoproteins (density, d < 1·21 g/ml) and agarose gel electrophoresis of lipoprotein-free plasma (d > 1·21 g/ml) to separate DBP (α globulin) from albumin. The recovery of the tracer in plasma proteins was always more than 80%. At physiological concentrations [³H]25-OH-D bound almost exclusively to DBP (98%), [³H]vitamin D or [¹⁴C]vitamin D bound both to DBP and to lipoproteins (40%), and [³H]1,25-(OH)₂-D bound to DBP (62%), to lipoproteins (15%) and also to albumin (23%). When the concentration of vitamin D metabolites was increased, DBP became saturated. The binding capacity of DBP was similar for all three sterols, about 5 μmol/l plasma, or one mole of sterol per mole of protein, but the saturating concentration was different for the three sterols (vitamin D > 1,25-(OH)₂-D > 25-OH-D). 25-OH-D had the greatest affinity for DBP, and it completely displaced both vitamin D and 1,25(OH)₂-D from DBP at higher concentrations. All sterols bound to both plasma lipoproteins and albumin: vitamin D preferentially to lipoproteins and both 25-OH-D and 1,25-(OH)₂-D to albumin. A similar binding pattern for vitamin D in plasma was observed previously by us in a child with vitamin D toxicity. The increased binding of vitamin D to lipoproteins and especially to albumin may help explain the pathogenesis of toxicity in hypervitaminosis D, where the plasma levels of the more active metabolites are insufficient to account for the clinical signs.     

The clinical significance of vitamin D levels and vitamin D receptor mRNA expression in colorectal neoplasms

Background/AimThis study aimed to investigate the clinical significance of changes in vitamin D [25(OH)D] levels and vitamin D receptor (VDR) mRNA expression in colorectal adenoma development.MethodsPlasma concentrations of 25(OH)D and mRNA expression of VDR in tissues were determined by enzyme‐linked immunosorbent assay (ELISA) and real‐time fluorescence quantitative polymerase chain reaction (RT‐qPCR), respectively. In addition, the concentration of plasma 25(OH)D and levels of VDR mRNA in tissues were compared among healthy individuals and adenoma and adenocarcinoma patients.ResultsVitamin D receptor expression in colorectal adenocarcinoma tissues was significantly lower than that in para‐cancerous tissues that were >5 cm away from malignant tumor sites (p < 0.01). The level of VDR expression in normal colorectal tissues from healthy individuals was significantly higher than that in colorectal adenomas (p < 0.01) and colorectal adenocarcinomas (p < 0.01); however, the VDR expression was not significantly different between colorectal adenomas and colorectal adenocarcinomas (p = 0.106). The concentration of 25(OH)D in healthy individuals was significantly higher than that in patients with colorectal adenomas (p < 0.01) and colorectal adenocarcinomas (p < 0.01); however, the concentration of 25(OH)D was not significantly different between colorectal adenomas and colorectal adenocarcinomas (p = 0.489). A low concentration of 25(OH)D was considered a risk factor for colorectal adenoma and colorectal adenocarcinoma, with odds ratios of 4.875 and 2.925, respectively.ConclusionsThe 25(OH)D levels and VDR mRNA expression might be associated with the development of colorectal adenoma and its progression to adenocarcinoma.     

大剂量普通维生素D和活性维生素D治疗甲状旁腺功能减退症的有效性和安全性比较

目的 比较大剂量普通维生素D和活性维生素D治疗甲状旁腺功能减退症的有效性和安全性.方法 将60例甲状旁腺功能减退症患者根据随机数字表法分为对照组与观察组,各30例.对照组给予活性维生素D,观察组给予大剂量普通维生素D.比较两组的实验室指标、临床疗效及不良反应发生情况.结果治疗后,两组的血钙水平、钙磷乘积均升高,血磷、全...     

7例化疗后迟发皮肤毒性反应的护理

总结了7例化疗后出现不明显外渗引起迟发皮肤毒性反应患者的护理。护士应加强对化疗药物外渗知识的学习,重视对输液部位的观察,当出现皮肤毒性迟发反应时应采取积极适当的措施,将外渗性皮肤组织损伤减少到最低限度。     

维生素D对脓毒性休克导致急性呼吸窘迫综合征患者的干预价值研究

目的探索维生素D对脓毒性休克致急性呼吸窘迫综合征（ARDS）的干预效果。 方法选取2017年6月至2019年6月入住山西医科大学第一医院重症监护室发生脓毒性休克导致ARDS的80例患者,根据25-羟维生素D水平分级分为维生素D正常组（17例,25-羟维生素D ≥ 50 nmol /L）和维生素D降低组（63例,25-羟维生素D < 50 nmol /L）。然后再根据25-羟维生素D水平的降低程度进一步将维生素D降低组分为维生素D缺乏组（35例,30 nmol /L ≤25-羟维生素D ≤ 49.9 nmol /L）和维生素D严重缺乏组（28例,25-羟维生素D <30 nmol/L）。采用随机数字表法将维生素D缺乏组患者分为A组（对照组,17例）和B组（干预组,18例）,将维生素D严重缺乏组患者分为C组（对照组,14例）和D组（干预组,14例）。A、C组患者给予经胃管、肠内营养管补充淀粉胶囊0.5 g/d;B、D组患者给予经鼻胃管、鼻肠管补充阿法骨化醇软胶囊0.5 g/d,疗程均为7 d。记录所有患者的年龄、性别、25-羟维生素D、氧合指数、急性病生理学和长期健康评价（APACHE）Ⅱ评分、血管外肺水指数（EVLWI）、肺血管通透性指数（PVPI）及28 d死亡情况,采用Cox回归分析影响脓毒性休克致ARDS患者28 d病死率的危险因素。 结果维生素D正常组和维生素D降低组患者25-羟维生素D [（57 ± 4）nmol /L vs.（33 ± 8）nmol /L]、氧合指数[（135 ± 25）mmHg vs.（114 ± 18）mmHg]、APACHEⅡ评分[（14.7 ± 1.6）分vs.（16.0 ± 2.0）分]、EVLWI [（11.4 ± 2.1）mL/kg vs.（14.5 ± 2.7）mL/kg]、PVPI [（3.61 ± 0.32）vs.（5.05 ± 0.68）]及28 d死亡情况（1/17 vs. 20 /63）比较,差异均有统计学意义（t = 11.448、3.872、8.864、5.097、8.409,χ² = 4.626;P均< 0.05）。Cox回归分析结果显示,25-羟维生素D [相对危险度= 4.183,95%置信区间（1.787,10.594）,P = 0.012]是脓毒性休克致ARDS患者预后的保护因素。且干预后,C、D组患者25-羟维生素D [（25 ± 4）nmol /L vs.（37 ± 4）nmol /L]、氧合指数[（152 ± 18）mmHg vs.（171 ± 13）mmHg]、APACHEⅡ评分[（12.8 ± 1.4）分vs.（11.0 ± 1.7）分]、EVLWI [（9.5 ± 0.9）mL /kg vs.（7.9 ± 1.4）mL /kg]及PVPI [（3.63 ± 0.28）vs.（2.95 ± 0.48）]比较,差异均有统计学意义（t = 7.493、3.246、3.016、3.420、4.373,P均< 0.05）,而28 d死亡情况（6 /14 vs. 4 /14）比较,差异无统计学意义（χ² = 0.622,P = 0.430）。 结论维生素D降低在脓毒性休克致ARDS患者中普遍存在,且维生素D是脓毒性休克ARDS患者28 d病死率的保护因素,而补充维生素D可改善维生素D严重缺乏者ARDS的严重程度。     

Role of vitamin D in arterial hypertension

Vitamin D deficiency is highly prevalent and may contribute to arterial hypertension. The antihypertensive effects of vitamin D include suppression of renin and parathyroid hormone levels and renoprotective, anti-inflammatory and vasculoprotective properties. Low 25-hydroxyvitamin D levels, which are used to classify the vitamin D status, are an independent risk factor for incident arterial hypertension. Meta-analyses of randomized controlled trials showed that vitamin D supplementation reduces systolic blood pressure by 2–6 mmHg. However, further studies are needed before drawing a final conclusion on the effect of vitamin D therapy on blood pressure and cardiovascular risk. In our current clinical practice we should take into account the high prevalence of vitamin D deficiency, the easy, cheap and safe way by which it can be supplemented and the promising clinical data suggesting that vitamin D might be useful for the treatment of arterial hypertension as well as other chronic diseases. Therefore, we recommend that testing for and treating vitamin D deficiency in patients with arterial hypertension should be seriously considered.     

维生素D对脂多糖致急性肺损伤大鼠肺组织血管紧张素转化酶2和维生素D受体表达水平的影响

目的 观察维生素D(vitamin D,Vit D)对脂多糖(lipopolysaccharide,LPS)致Wistar大鼠急性肺损伤(acute lung injury,ALI)肺组织中血管紧张素转化酶2(angiotensinconverting enzyme 2,ACE2)和维生素D受体(vitamin D receptor,VDR)表达水平的影响.方法 采用尾静脉注射LPS方法制备大鼠ALI模型;将30只健康雄性Wistar大鼠随机(随机数字法)分为6组:正常对照组(NC组)、LPS组:尾静脉注射LPS 5mg/kg、Vit D组:给予Vit D活性形式(骨化三醇)25 μg/kg连续灌胃3d和(LPS+ Vit D) 1-3组:分别于骨化三醇1μg/kg、5μg/kg、25 μg/kg灌胃3d后尾静脉注射LPS 5mg/kg,所有大鼠于注射LPS的24 h后进行后续实验.分别观察大鼠一般情况,肺组织病理及肺干/湿重比变化、肺组织中VDR、ACE2蛋白及基因水平的表达.结果 LPS组大鼠病态表现(呼吸浅快、精神萎靡、口鼻可见血性分泌物)明显,(LPS+ VitD) 1-3组病态表现和肺组织病理损伤均较LPS组明显减轻.LPS组VDR和ACE2蛋白及基因水平的表达均较NC组和Vit D组显著降低(P＜0.05),(LPS+ VitD) 1-3组各组VDR和ACE2蛋白及基因水平的表达均较LPS组有所升高(P＜0.05),但仍显著低于Vit D组(P＜0.05),其中(LPS+ Vit D) 1-3组各组VDR蛋白及基因水平的表达差异无统计学意义(P＞0.05),ACE2的表达差异有统计学意义(P＜0.05).结论 Vit D能使LPS致ALI大鼠肺组织中ACE2和VDR蛋白及基因表达水平增加,故此推测ACE2和VDR表达增加可能对ALI的发生、发展起保护作用.