Effect of High-Dose Vitamin D3 Intake on Ambulation, Muscular Pain and Bone Mineral Density in a Woman with Multiple Sclerosis: A 10-Year Longitudinal Case Report

Mounting evidence correlate vitamin D3 (cholecalciferol) supplementation or higher serum levels of vitamin D (25(OH)D) with a lower risk of developing multiple sclerosis (MS), reduced relapse rate, slower progression or fewer new brain lesions. We present here the case of a woman who was diagnosed with MS in 1990. From 1980 to 2000, her ability to walk decreased from ~20 to 1 km per day. Since January 2001, a vitamin D3 supplement was ingested daily. The starting dose was 20 mcg (800 IU)/day and escalated to 100 mcg (4000 IU)/day in September 2004 and then to 150 mcg (6000 IU)/day in December 2005. Vitamin D3 intake reduced muscular pain and improved ambulation from 1 (February 2000) to 14 km/day (February 2008). Vitamin D intake over 10 years caused no adverse effects: no hypercalcaemia, nephrolithiasis or hypercalciuria were observed. Bowel problems in MS may need to be addressed as they can cause malabsorption including calcium, which may increase serum PTH and 1,25(OH)2D levels, as well as bone loss. We suggest that periodic assessment of vitamin D3, calcium and magnesium intake, bowel problems and the measurement of serum 25(OH)D, PTH, Ca levels, UCa/Cr and bone health become part of the integral management of persons with MS.     

Recent Developments of 19‐Nor‐1,25‐dihydroxyvitamin D3 Analogues

The vitamin D hormone, 1α,25‐dihydroxyvitamin D₃ [1,25‐(OH)₂D₃], exerts its hormonal effects predominantly on intestine, bone, and kidney, where it plays a crucial role in calcium and phosphorus homeostasis and bone mineralization. In addition to its classical actions, 1,25(OH)₂D₃ exerts pleiotropic effects in a wide variety of target tissues and cell types, often in an autocrine/paracrine fashion. These biological activities of 1,25(OH)₂D₃ have suggested a multitude of potential therapeutic applications for the vitamin D hormone in the treatment of hyperproliferative disorders (e.g. cancer and psoriasis), immune dysfunction (autoimmune diseases), and endocrine disorders (e.g. hyperparathyroidism). However, the calcemic effects induced by 1,25(OH)₂D₃—hypercalcemia, increased bone resorption, and soft tissue calcification—limit the use of the natural ligand in these clinical applications. Therefore, numerous 1,25(OH)₂D₃ analogues have been synthesized with the intent of producing therapeutic agents devoid of hypercalcemic and hyperphosphatemic side effects. To this aim, much attention has been focused on the development of 19‐nor‐vitamin D₃ derivatives that lack the ring‐A exocyclic methylene group (C19). In this review, the 19‐nor‐1,25(OH)₂D₃ analogues are classified according to modifications made at the A‐ring, the side chain, or both the A‐ring and side chain, as well as other positions. The biological activities of these 19‐nor‐1,25(OH)₂D₃ analogues are summarized and their structure–activity relationships and binding features with the vitamin D receptor (VDR) are discussed.     

Expression of Vitamin D Receptor (VDR) Positively Correlates with Survival of Urothelial Bladder Cancer Patients

Vitamin D3 shows tumoristatic and anticancer effects by acting through the vitamin D receptor (VDR), while hydroxylation of 25-hydroxyvitamin D3 at position 1α by CYP27B1 is an essential step in its activation. The expression of both the VDR and CYP27B1 has been found in many normal and cancer tissues, but there is a lack of information about its expression in human bladder cancers. The aim of the present research was to examine whether the expression of the VDR and CYP27B1 in bladder cancer was related to the prognostic markers and disease outcome. We analyzed VDR and CYP27B1 in samples of tumor and normal tissues obtained from 71 urinary bladder cancer patients. The highest VDR immunostaining was found in normal epithelium and was significantly lower in bladder cancer cells (p < 0.001 with Mann–Whitney U test). VDR expression was lowest in more advanced (pT2b–pT4) (p = 0.005 with Mann–Whitney U test) and metastasizing cancers (p < 0.05 and p = 0.004 with Mann–Whitney U test for nuclear and cytoplasmic VDR immunostaining, respectively). The lack of cytoplasmic and nuclear VDR was also related to shorter overall survival (for cytoplasmic VDR immunolocalization 13.3 vs. 55.3 months of survival, HR = 1.92, p = 0.04 and for nuclear VDR immunostaining 13.5 vs. 55.3 months of survival, HR = 2.47, p = 0.002 with Mantel-Cox test). In cases with the lack of high cytoplasmic VDR staining the non-classic differentiations (NDs) was observed in higher percentage of tumor area. CYP27B1 expression was lower in cancer cells than in normal epithelial cells (p = 0.03 with Mann–Whitney U test), but its expression did not correlate with tumor stage (pT), metastasizing, grade, mitotic activity or overall survival. In conclusion, expression of the VDR and CYP27B1 are deregulated in urothelial bladder cancers. Although our results showing a relationship between the decreased VDR expression and prognostic markers and survival time indicate potential usefulness of VDR as a new indicator of a poorer prognosis, further studies are needed in different patient cohorts by independent groups to validate this hypothesis. We also suggest that vitamin D-based therapies may represent an adjuvant strategy in treatment for bladder cancers expressing VDR.     

25(OH)D Is Effective to Repress Human Cholangiocarcinoma Cell Growth through the Conversion of 25(OH)D to 1α,25(OH)2D3

Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1α,25(OH)₂D₃, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1α,25(OH)₂D₃, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1α,25(OH)₂D₃ has been found in some cancer cells with CYP27B1 expression. In this study, CYP27B1 expression was demonstrated in CCA cells and human CCA specimens. 25(OH)D effectively represses SNU308 cells growth, which was strengthened or attenuated as CYP27B1 overexpression or knockdown. Lipocalcin-2 (LCN2) was also found to be repressed by 25(OH)D. After treatment with 800 ng/mL 25(OH)D, the intracellular 1α,25(OH)₂D₃ concentration was higher in SNU308 cells with CYP27B1 overexpression than wild type SNU308 cells. In a xenograft animal experiment, 25(OH)D, at a dose of 6 μg/kg or 20 μg/kg, significantly inhibited SNU308 cells’ growth without inducing obvious side effects. Collectively, our results indicated that SNU308 cells were able to convert 25(OH)D to 1α,25(OH)₂D₃ and 25(OH)D CYP27B1 gene therapy could be deemed as a promising therapeutic direction for CCA.     

1,25-二羟维生素D_3对成骨细胞增殖和分化的影响

成骨细胞是人和高等动物体内重要的功能细胞,在骨形成、骨发生以及骨内物质更新工程中发挥着重要的作用。1,25-二羟维生素D_3对成骨细胞的增殖和分化等过程具有重要影响。     

Does Vitamin D Work Synergistically with Anti-Asthmatic Drugs in Airway Remodeling?

Vitamin D is commonly known for its properties of airway remodeling inhibition. Due to this, we decided to analyze the action of calcitriol with anti-asthmatic drugs in airway remodeling. The HFL1 cell line was treated with calcitriol, beclomethasone 17-propionate, montelukast sodium, LTD4 and TGF-β in different combinations. Real-time PCR was used to analyzed the expression of ACTA2, CDH-1, Vimentin, ADAM33, MMP-9 and CysLTR1 on the mRNA level, whereas Western blot was used to analyze gene expression on the protein level. One-way analysis variants, the Kruskal-Wallis test, Student’s t-test or Welch’s t-test were used for statistical analysis. Concerning the results, pre-treatment with calcitriol increased the inhibitory effect of beclomethasone 17-propionate and montelukast sodium on the expression of ACTA2 (p = 0.0072), Vimentin (p = 0.0002) and CysLTR1 (p = 0.0204), and 1,25(OH)₂D₃ had an influence on the effects of beclomethasone 17-propionate and montelukast sodium and of CDH1 expression (p = 0.0076). On the protein level, pre-treatment with calcitriol with beclomethasone 17-propionate and montelukast sodium treatment decreased ACTA2 expression in comparison to the LT (LTD4 and TGF-β) control group (p = 0.0191). Hence, our study not only confirms that vitamin D may inhibit airway remodeling, but also shows that vitamin D has a synergistic effect with anti-asthmatic drugs.     

氢氧化铝和氢氧化锶复合粉末的制备及热处理

采用活化铝-锶合金粉末水解反应制备氢氧化铝和氢氧化锶复合粉末，并在700℃下进行热处理，利用XRD，SEM，BET和TG—DTG等分析技术对复合粉末结构、性能及热处理进行研究。结果表明，铝-锶合金粉末水解反应产物为氢氧化铝和氢氧化锶的复合粉末，微观形貌为1～3μm片状小颗粒叠加的团聚颗粒，BET比表面积较大。达到45．2m^2／g。TG—DTG结果显示，在70～190℃，八水氢氧化锶中8个结晶水脱水，在190～650℃，氢氧化铝和氢氧化锶热分解。经700℃下热处理1h后，其相组成、微观形貌、BET比表面积都将发生较大的变化。     

高效液相色谱法测定化妆品中VD2及VD3

采用高效液相色谱法对VD2及VD3进行测定,以甲醇/乙腈(90∶10)为流动相,流速为1.0 mL/min,DAD检测器,C18柱,检测波长260 nm,得到在0.50～50.0 mg/L浓度范围内有较好的线性关系,相关系数分别为rVD2=0.999 4和rVD3=0.999 5,回收率为96.9%～100.6%,方法检出限VD2为0.13 mg/L,VD3为0.06 mg/L。该方法快速方便,可用于化妆品VD2及VD3的检测。     

光化学合成维生素D2和D3

综述了光化学法合成维生素Ｄ２和Ｄ３的研究进展。     

新型无机阻燃剂的研究进展

综述了新型无机阻燃剂的性能和制备方法 ,重点介绍了国内外关于氢氧化镁阻燃剂的研究进展情况以及纳米氢氧化镁的制备方法。建议我国应加大对新型无机阻燃剂的研究和推广应用的力度     

多元阻燃体系对HDPE的阻燃研究

本文研究了氢氧化铝，１，２－双三溴苯氧基乙烷，氧化锑三元复合体系对ＨＤＰＥ阻燃性能和拉伸性能的影响，还研究了在该三元体系中，加入ＣＰＥ时，ＨＤＰＥ的阻燃及拉伸性能的变化。实验结果表明，上述两阻燃体系均能使ＨＤＰＥ具有良好的阻燃性，但材料的伸强度和伸长率有一定程度的下降。     

甲醇分解铝酸钠溶液制备大颗粒氢氧化铝的工艺与表征

对甲醇分解NaAl(OH)4溶液制备大颗粒Al(OH)3进行了工艺研究,考察了分解温度、分子比(Na2O/Al2O3摩尔比)、Na2O浓度、硅量指数(Al2O3/SiO2质量比)、搅拌速度和甲醇用量对产品粒度和形貌的影响. 结果表明,在NaAl(OH)4溶液的Na2O浓度为180 g/L、分子比为1.5~1.6,硅量指数550以上及甲醇与NaAl(OH)4溶液等体积的优化条件下,控制分解温度60℃,可得到平均粒径达80 mm的球形Al(OH)3. 甲醇的加入改变了Al(OH)3生长基元的径向和轴向生长速率,甲醇量越大,径向生长速率越快,生长基元越薄. 当甲醇与NaAl(OH)4溶液体积比为1:1时,Al(OH)3生长基元的厚度在100 nm左右. 随分解温度升高,Al(OH)3由Bayerite型向Gibbsite型转变,热重-差热值与理论值吻合.