维生素D原体浓度对它的光异构反应的影响

目的：研究乙醇溶液中维生素 Ｄ 原体浓度对它的光异构反应产物产率的影响。方法：用两种紫外光激发光源光照不同浓度的维生素 Ｄ 原体乙醇溶液，使用正相 Ｈ Ｐ Ｌ Ｃ 系统定量测定主要光异构物在溶液中的浓度。结果：数据表明，随维生素 Ｄ 原体浓度的增加，速甾醇产率减少，而光甾醇产率明显增加。维生素 Ｄ 前体产率变化，与所用的激发光源有关。结论：维生素 Ｄ 原体浓度对其光异构反应产物产率的影响较大，特别对速甾醇和光甾醇，利用光自吸收效应有助于设计光化学法合成药物及制备高产率的光异构产物。     

婴幼儿维生素D缺乏调查及维生素D补充对血清25-羟维生素D水平的影响

目的 调查婴幼儿维生素D缺乏情况及探讨维生素D补充对血清25-羟维生素D[25-(OH)D]水平的影响.方法 378例婴幼儿按月龄分为A组(0-6个月,142例)、B组(7-12个月,168例)和C组(13-36个月,68例).其中,部分婴幼儿近3个月口服不同剂量维生素D 250 IU/d(D组,46例)、300 IU/d(E组,82例)和500 IU/d(F组,171例),79例未补充维生素D(G组).采集婴幼儿指尖血,用酶联免疫法检测血清25-(OH)D水平,计算维生素D缺乏发生率.结果 婴幼儿维生素D缺乏发生率为21.16％(80/378).B组血清25-(OH)D水平高于A、C组[(72.0±23.2)nmol/L vs.(67.0±24.8)、(55.9±12.4)nmol/L](P＜0.05),而维生素D缺乏发生率低于A、C组(13.10％ vs.21.83％、39.71％) (P＜0.05).D、E、F组血清25-(OH)D水平均高于G组[(63.6±16.9)、(69.9±20.1)、(71.5±27.8)nmol/L vs.(57.2±11.9) nmol/L] (P＜0.05),而维生素D缺乏发生率均低于G组[26.09％、21.95％、13.45％ vs.34.18％](P＜0.05);D、E组维生素D缺乏发生率高于F组(P＜0.05).结论 婴幼儿维生素D普遍缺乏,建议补充维生素D500 IU/d,0-6个月和13-36个月的婴幼儿维生素D缺乏情况应予重视.     

不同维生素D注射剂对健康女性血25羟维生素D水平的影响

目的比较维生素D2注射液与维生素D3注射液在治疗健康女性维生素D缺乏或不足时对血25羟维生素D水平的影响。方法选择常住成都市且年龄在40-55岁的健康女性94名,随机将其分为D2组和D3组各47例。D2组给予维生素D2注射液,每次7.5mg（30万U）,每2周注射1次,共注射4次;D3组给予维生素D3注射液,每次7.5mg（30万U）,每2周注射1次,共注射4次。分别于治疗前、最后1次注射后2周采静脉血测定血清25羟维生素D,血清钙、磷、镁,血清甲状旁腺素（PTH）及血清骨源性碱性磷酸酶（BAP）。结果治疗后,D2组和D3组血清25羟D水平明显升高,差异有统计学意义（P〈0.01）;且治疗后D3组25羟D水平高于D2组,差异有统计学意义（P〈0.01）。治疗前后,2组血清磷、血清PTH均降低,差异有统计学意义（P〈0.01）,血清钙、血清镁、血清BAP无明显变化,差异无统计学意义（P〉0.05）。未出现维生素D中毒或药物相关不良反应表现。结论维生素D针剂无论是D2还是D3治疗维生素D缺乏或不足都是有效的,但在相同用法条件下D3比D2升高血清25羟D水平的幅度更大。维生素D注射剂30万U每2周1次共4次治疗维生素D不足或缺乏是安全的。     

不同剂量活性维生素D对大鼠细胞自噬的影响

目的探讨在生理状况下不同剂量活性维生素D3(VD3)干预下老年大鼠是否发生细胞自噬,以及发生自噬的情况。方法 18月龄SD大鼠32只按体质量随机分为4组:A组:对照组;B组:低剂量活性VD3组[(0.01μg/kg)/d];C组:中剂量活性VD3组[(0.1μg/kg)/d];D组:高剂量活性VD3组[(0.4μg/kg)/d]。经过5个月灌胃不同剂量活性VD3干预后处死,取1mm3肝脏组织4℃保存,取其余肝组织,生理盐水冲洗,锡纸包裹-80℃保存。透射电镜观察大鼠肝脏细胞自噬情况。通过western-blot的方法测定自噬小体标志物LC3对细胞的自噬活性进行半定量分析。结果在生理状况下不同剂量活性维生素D的干预导致大鼠细胞自噬泡与胞浆的比值:A、B、C、D四组大鼠自噬泡与胞浆比值之间差异有统计学意义(P<0.05)。两两比较结果,A组与B、C、D组差异都有统计学意义(P<0.05),B组和C组之间差异没有统计学意义(P>0.05),B组和C组都与D组差异有统计学意义(P<0.05)。LC3II/LC3I结果与大鼠细胞自噬泡与胞浆的比值相同。结论在生理状况下长期大剂量给予不同剂量活性维生素D可对老年大鼠细胞自噬产生不同影响。     

柱切换高效液相色谱法测定维生素D滴剂、维生素AD滴剂中维生素D的含量

目的:建立用于快速测定维生素D滴剂、维生素AD滴剂中维生素D含量的柱切换二维液相色谱方法.方法:样品用正己烷溶解后直接注入液相色谱系统,在第一维色谱完成前维生素D3、维生素D3的初步净化;以9 mL大体积的收集流路收集合有前维生素D3、维生素D3的组分,在第二维色谱完成前维生素D3与维生素D3的分离和定量.本方法可以直...     

两生花——钙和维生素D

钙与维生素D密不可分。维生素D缺乏，钙的吸收和利用会受到影响，称为钙相对缺乏。相反，钙源不足，即使有充足的维生素D，也会缺钙，称为钙绝对缺乏。     

孕晚期补充维生素D对母儿25羟维生素D水平及新生儿疾病的影响

目的　探讨孕晚期补充维生素D对母儿25羟维生素D［25（OH）D］水平、新生儿体格发育及新生儿疾病的影响。方法　收集2019年1月至2021年12月在厦门大学附属中山医院及厦门大学附属第一医院定期产检并分娩的孕产妇及新生儿作为研究对象,随机分为干预组（316例）和对照组（337例）。干预组<35岁269例,≥35岁47例;对照组<35岁283例,≥35岁54例。干预组自妊娠28周至分娩每日补充维生素D≥600 IU,对照组每日补充维生素D <600 IU。检测孕产妇分娩前及新生儿25（OH）D水平,测量新生儿体质量、身长、头围,统计分娩方式、早产比例及新生儿疾病的发生率。行独立样本t检验、χ²检验。结果　干预组孕产妇分娩前及新生儿25（OH）D水平分别为（27.91±7.56）μg/L、（16.24±4.31）μg/L,均高于对照组（24.65±6.83）μg/L、（12.60±3.97）μg/L,差异均有统计学意义（均P<0.001）;干预组孕产妇分娩前及新生儿出生后维生素D缺乏率分别为19.62%（62/316）、17.09%（54/316）,均低于对照组47.18%（159/337）、49.26%（166/337）,差异均有统计学意义（均P<0.001）。干预组新生儿出生体质量、身长、头围均高于对照组（均P<0.05）;干预组新生儿早发型败血症、新生儿坏死性小肠结肠炎的发生率分别为1.27%（4/316）、2.53%（8/316）,均低于对照组4.15%（14/337）、6.23%（21/337）,差异均有统计学意义（均P<0.05）;两组孕产妇剖宫产率及早产率差异均无统计学意义（均P>0.05）。结论　孕晚期每日补充维生素D≥600 IU可以提高孕产妇及新生儿血清25（OH）D水平、促进新生儿体格发育并降低新生儿期重症疾病的发生率,但对孕产妇剖宫产率及早产的发生率不产生影响。     

正相-反相两步高效液相色谱法制备毫克量级维生素D_3异构体

利用正相半制备柱和反相分析柱的两步高效液相色谱法,在实验室规模制备了毫克是级维生素D_3的三个重要异构体——维生素D_3前体、光甾醇_3和速甾醇_3·维生素D_3原体,7-去氢胆固醇的光照是在一个装有UVB荧光灯的光治疗室中进行。采用紫外分光光度法和高效液相色谱法对制得的三个异构体进行了定性定量分析。在这三个异构体检测极限下,除了维生素D_3前体中有不超过0.25％的维生素D_3杂质外,三个产品中均没有发现任何除它本身之外的其他异构体杂质。     

补充维生素D2与维生素D3的应用评价

维生素D是一种治疗儿童佝偻病和老年骨质疏松的重要药物,分为维生素D2与维生素D3.目前,医药市场上出现的维生素D制剂,其成分有的是维生素D2,有的是维生素D3.本综述从维生素D2与维生素D3的疗效、临床应用及其补充途径等方面进行比较评价.     

EFFECT OF SHORT COURSE OF 1,25-DIHYDROXYVITAMIN D3ON BIOCHEMICAL MARKERS OF BONE REMODELLING IN POSTMENOPAUSAL WOMEN

This study was designed to test the hypothesis that a short treatment course of 1,25(OH)₂D₃elicits a stimulation of osteoblast activity without any action on the osteoclast. To test this, oral daily doses of 0.5μg or 1μg of 1,25(OH)₂D₃were administered for 7 days to two groups (n=5 andn=7, respectively) of postmenopausal women with low bone mineral density. Markers of osteoblast activity, i.e. osteocalcin (BGP), total alkaline phosphatase activity (ALP) and bone alkaline phosphatase activity (BALP), and markers of osteoclast activity, i.e. hydroxylysyl-pyridinoline (Pyr), lysyl-pyridoline (D-Pyr), and galactosyl-hydroxylysine (GHyl) were measured in plasma and in fasting urinary samples, respectively, at sequential times during and after 1,25(OH)₂D₃administration. It resulted that short term 1μg 1,25(OH)₂D₃oral administration induced a significant (P<0.05) rise of BGP serum level without any associated increase ofD-Pyr and GHyl, the latter also expressed as GHyl to GGHyl ratio. Urinary Pyr increased significantly after 1μg daily doses of 1,25(OH)₂D₃. Thus, a short course of 1μg daily doses of 1,25(OH)₂D₃elicits a stimulation of osteoblast activity without any enhancement ofD-Pyr, the most specific marker of osteoclast activity. The enhancement of Pyr after 1μg daily doses of 1,25(OH)₂D₃might be due to the activation of extraosseous metabolic pathways rather than to the activation of osteoclast.     

正相-反相两步高效液相色谱法制备毫克量级维生素D3异构体

利用正相半制备柱和反相分析柱的两步高效液相色谱法,在实验室规模制备了毫克是级维生素D₃的三个重要异构体——维生素D₃前体、光甾醇₃和速甾醇₃·维生素D₃原体,7-去氢胆固醇的光照是在一个装有UVB荧光灯的光治疗室中进行。采用紫外分光光度法和高效液相色谱法对制得的三个异构体进行了定性定量分析。在这三个异构体检测极限下,除了维生素D₃前体中有不超过0.25%的维生素D₃杂质外,三个产品中均没有发现任何除它本身之外的其他异构体杂质。     

3种抗真菌生药活性成分对两种真菌细胞遗传物质的影响

目的　研究抗真菌生药活性成分对真菌细胞遗传物质的影响,以期发现其抗真菌的作用机理。方法　把对照组及用药组真菌细胞进行激光扫描共聚焦显微镜观察并作细胞扫描图像分析,从而定量描述细胞形状、面积和DNA,RNA含量。结果　用药组细胞形态及DNA,RNA含量发生不同变化。结论　澳洲茄胺、紫檀　和白鲜碱直接或间接影响了真菌细胞遗传物质的正常合成以至不能完成正常细胞周期,从而抑制真菌生长甚至导致死亡。     

Metabolism of 26,26,26,27,27,27-F6-1alpha,25-dihydroxyvitamin D3 by CYP24: species-based difference between humans and rats

The compound 26,26,26,27,27,27-F(6)-1alpha,25(OH)(2)D(3) is a hexafluorinated analog of the active form of Vitamin D(3). The enhanced biological activity of F(6)-1alpha,25(OH)(2)D(3) is considered to be related to a decreased metabolic inactivation of the compound in target tissues such as the kidneys, small intestine, and bones. Our previous study demonstrated that CYP24 is responsible for the metabolism of F(6)-1alpha,25(OH)(2)D(3) in the target tissues. In this study, we compared the human and rat CYP24-dependent metabolism of F(6)-1alpha,25(OH)(2)D(3) by using the Escherichia coli expression system. In the recombinant E. coli cells expressing human CYP24, bovine adrenodoxin and NADPH-adrenodoxin reductase, F(6)-1alpha,25(OH)(2)D(3) was successively converted to F(6)-1alpha,23S,25(OH)(3)D(3), F(6)-23-oxo-1alpha,25(OH)(2)D(3), and the putative ether compound with the same molecular mass as F(6)-1alpha,25(OH)(2)D(3). The putative ether was not observed in the recombinant E. coli cells expressing rat CYP24. These results indicate species-based difference between human and rat CYP24 in the metabolism of F(6)-1alpha,25(OH)(2)D(3). In addition, the metabolite with a cleavage at the C(24)z.sbnd;C(25) bond of F(6)-1alpha,25(OH)(2)D(3) was detected as a minor metabolite in both human and rat CYP24. Although F(6)-1alpha,23S,25(OH)(3)D(3) and F(6)-23-oxo-1alpha,25(OH)(2)D(3) had a high affinity for Vitamin D receptor, the side-chain cleaved metabolite and the putative ether showed extremely low affinity for Vitamin D receptor. These findings indicate that human CYP24 has a dual pathway for metabolic inactivation of F(6)-1alpha,25(OH)(2)D(3) while rat CYP24 has only one pathway. Judging from the fact that metabolism of F(6)-1alpha,25(OH)(2)D(3) in rat CYP24-harboring E. coli cells is quite similar to that in the target tissues of rat, the metabolism seen in human CYP24-harboring E. coli cells appear to exhibit the same metabolism as in human target tissues. Thus, this recombinant system harboring human CYP24 appears quite useful for predicting the metabolism and efficacy of Vitamin D analogs in human target tissues before clinical trials.     

阿魏酸钠对花生四烯酸代谢的影响

利用放射薄层方法测定兔血小板花生四烯酸代谢产物TXB₂,PGE₂和PGF_2α。用放射免疫法测定兔血小板TXB₂及主动脉6-keto-PGF_1α。阿魏酸钠(SF,0.1～3.2 mmol/L),抑制¹⁴C-花生四烯酸转化为TXB₂,呈剂量效应关系,IC₅₀为0.762 mmol/L。SF在较高浓度(0.8～3.2mmol/L)时亦抑制PGE₂,PGF_2α的生成。用放免法观察到,SF对血小板TXB₂和动脉壁6-keto-PGF_1α的生成均有抑制作用,对TXB₂的作用较强。结果提示,SF可抑制兔血小板和动脉壁环氧酶活性。     

白三烯C4（LTC4）放射受体结合方法的建立及二苯乙烯低聚体和LTC4受体结合特性

目的：建立LTC₄放射受体结合实验方法,并比较二苯乙烯低聚体（Gn-3）和LTC₄受体的结合特性。方法：以豚鼠肺膜为实验材料,采用³H-LTC₄为放射配体,以FPL₅₅₇₁₂作阳性对照药物,Gn-3为实验药物,进行药物竞争结合实验。采用离体器官生物检测法鉴定Gn-3对LTC₄受体的拮抗作用。结果：3H-LTC₄与其相应受体呈现单一结合位点,Gn-3可明显取代3H-LTC₄与其受体结合。生物学检定法证实Gn-3可抑制LTC₄引起的生物学效应。 结论：豚鼠肺膜LTC₄受体为单一结合位点受体,Gn-3为高活性的LTC₄受体拮抗剂。     

人参叶微量新成分的研究

从人参(Panax ginseng C.A.Meyer)叶中分离出14种单体化合物。其中4种微量成分用IR、MS、¹HNMR、13CNMR及化学方法等分别鉴定为20(R)-原人参三醇(Ⅰ)、胡萝卜甙(Ⅱ)、3β,12β-二羟基-20(22),24-达玛二烯—3—0—β—D—葡萄吡喃糖甙(Ⅲ)及20(R)-原人参二醇—3—0—β—D—葡萄吡喃糖甙(Ⅳ)。其中Ⅲ及Ⅳ系新化合物,分别命名为人参皂甙-Rh₃(ginsenoside-Rh₃)及20(R)-人参皂甙-Rh₃[20(R)-ginsenoside-Rh₂]。     

Chronic contamination with 137Cesium affects Vitamin D3 metabolism in rats

Twenty years after Chernobyl disaster, many people are still chronically exposed to low dose of (137)Cs, mainly through the food consumption. A large variety of diseases have been described in highly exposed people with (137)Cs, which include bone disorders. The aim of this work was to investigate the biological effects of a chronic exposure to (137)Cs on Vitamin D(3) metabolism, a hormone essential in bone homeostasis. Rats were exposed to (137)Cs in their drinking water for 3 months at a dose of 6500 Bq/l (approximately 150 Bq/rat/day), a similar concentration ingested by the population living in contaminated territories in the former USSR countries. Cytochromes P450 enzymes involved in Vitamin D(3) metabolism, related nuclear receptors and Vitamin D(3) target genes were assessed by real time PCR in liver, kidney and brain. Vitamin D, PTH, calcium and phosphate levels were measured in plasma. An increase in the expression level of cyp2r1 (40%, p<0.05) was observed in the liver of (137)Cs-exposed rats. However a significant decrease of Vitamin D (1,25(OH)D(3)) plasma level (53%, p=0.02) was observed. In brain, cyp2r1 mRNA level was decreased by 20% (p<0.05), while the expression level of cyp27b1 is increased (35%, p<0.05) after (137)Cs contamination. In conclusion, this study showed for the first time that chronic exposure with post-accidental doses of (137)Cs affects Vitamin D(3) active form level and induces molecular modifications of CYPs enzymes involved its metabolism in liver and brain, without leading to mineral homeostasis disorders.