1,25-(OH)2D3对哮喘小鼠肺内TIM-4表达的影响

目的：建立小鼠哮喘气道重塑模型,观察1,25-(OH)2D3对哮喘小鼠气道结构及T细胞免疫球蛋白域粘蛋白域蛋白-4（T cell immunoglobulin mucin protein-4, TIM-4）表达的影响。方法：30只BALB/c雌性小鼠随机分为对照组、哮喘组和1,25-(OH)2D3干预组,采用卵清蛋白致敏、激发建立哮喘模型。取小鼠肺组织,采用苏木精-伊红染色观察气道重塑情况,并应用RT-PCR法和免疫组化法检测肺内TIM-4 mRNA和蛋白的表达。结果：哮喘组发生典型的气道重塑改变,与对照组比较,TIM-4表达水平升高（105±9 vs 42±5,P<0.05）;1,25-(OH)2D3干预组较哮喘组气道重塑有所改善,TIM-4表达降低（78±6）,差异有统计学意义（P<0.05）。结论：TIM-4可能参与小鼠气道重塑过程;新型免疫调节剂1,25-(OH)2D3可下调哮喘小鼠肺内TIM 4的表达,改善气道重塑。     

经玻璃紫外线照射对大鼠25-羟维生素D水平及骨代谢的影响

目的：目前研究发现B型紫外线照射与血清25-羟维生素D［25-hydroxy vitamin D, 25-（OH）D］水平有剂量-效应关系,并且维生素D与骨代谢相关。该研究探讨经玻璃紫外线照射对大鼠25-（OH）D及骨代谢的影响。方法：选用30只Wistar大鼠建立不同紫外线暴露方式的动物模型,饲以缺乏维生素D饮料,随机分为避光组,紫外线直接照射160 min组,简称直射组,紫外线经单层玻璃照射160 min组,简称经玻组。每组各10例。21 d实验结束时,测定各组大鼠血清25-(OH) D、甲状旁腺激素(parathyroid hormone, PTH)、骨碱性磷酸酶(bone alkaline phosphatase, BALP)、骨钙素(osteocalcin, OC)和骨Ⅰ型胶原羧基末端肽(carboxyterminal cross-linked telopeptide of type I collagen, ICTP)的浓度及骨密度(bone mieral density, BMD)。结果：经玻组骨密度（BMD）为0.036±0.002 g/cm2,显著高于避光组(P<0.01); ICTP浓度0.181±0.067 μg/L,显著低于避光组(P<0.01);PTH、25-（OH）D、BALP及OC浓度分别为3.72±0.38 pg/mL、28.67±1.35 nmol/L、25.03±4.65 μg/mL和0.559±0.067 ng/mL,与避光组差异无显著性（P>0.05）。 经玻组BALP和ICTP水平及BMD与直射组差异无显著性(P>0.05);OC和PTH浓度显著高于直射组(P<0.05);25-（OH）D水平显著低于直射组（P<0.01）。结论：经单层玻璃的紫外线照射不能显著提高血浆25-（OH）D水平,但可降低维生素D缺乏造成的骨转化率升高并提高骨密度,与直接紫外线照射达到相似效果。［中国当代儿科杂志,2009,11（2）：138-141］     

学龄前儿童血清25羟维生素D调查分析

目的 调查5月份苏州地区部分学龄前儿童血清25羟维生素D［25（OH）D］水平,为儿童摄入及补充维生素D提供依据。方法 2012年5月选取苏州城区及郊区来苏州大学附属儿童医院体检的学龄前儿童852名为研究对象, 年龄3～7岁, 其中男454名、 女398名。分为3～4岁、 ＞4～5岁、 ＞5～6岁和＞6～7岁4组。测定身高和体重, 以体重指数（BMI）评价儿童体型分为超重与非超重组, 肥胖与非肥胖组。采用ELISA法测定所有研究对象血清25（OH）D水平。结果 3～4岁血清25（OH）D高于＞4～5岁、 ＞5～6岁、 ＞6～7岁3组, 差异有统计学意义（χ2依次为110.43、 216.54和198.18, P均＜0.05）; ＞4～5岁血清25（OH）D高于＞5～6岁、＞6～7岁两组, 差异有统计学意义（χ2分别为106.11和87.75, P均＜0.05）。361例（42.37%）存在血清25（OH）D缺乏, 344例（40.38%）存在血清25（OH）D不足。不同性别间血清25（OH）D差异无统计学意义（χ2 = 1.23, P＞0.05）。超重与非超重儿童血清 25（OH）D 分布分别为 53.97（45.27～66.45） nmol/L和52.64 （42.85～63.80） nmol/L; 而肥胖与非肥胖儿童分别为55.24（47.29～66.56） nmol/L和 52.71（43.11～63.92） nmol/L,组间血清25（OH）D分布差异均有统计学意义（χ2分别为7.10和6.73,P均＜0.05）。血清25 （OH）D与 BMI 呈正相关 （r = 0.11,P＜0.05）。结论 所调查苏州地区部分学龄前儿童血清 25（OH）D 总体不足。儿童血清25（OH）D与BMI呈正相关。应加强血清25（OH）D监测,并采取科学措施加强学龄前儿童维生素D摄入及补充。     

高压氧影响离体神经干细胞分化的量效及时效关系

目的：探讨不同压力和不同稳压时间下高压氧(HBO)对离体神经干细胞（NSCs）分化的影响,旨在找出HBO治疗的最佳压力与稳压时间。方法：取出生3日内新生Sprague-Dawley大鼠的脑皮质组织,在含B27、bFGF和EGF的DMEM/F12培养基中悬浮培养NSCs。将传至2~3代的NSCs随机分为不做处理的对照组（CON）和HBO处理组。HBO处理组根据所用压力和稳压时间分为6组：NSCs分别给予1个绝对大气压（ATA）、2 ATA、3 ATA 的HBO处理,每种压力再分别给予30和60 min两种稳压时间。HBO后继续培养24 h,7组细胞在同一时间行免疫荧光染色,荧光显微镜下观察NSCs分化为NSE阳性细胞的百分率。结果：NSCs分化为NSE阳性细胞的分化率从低到高依次为CON组（3.72±0.88%）,1ATA-30min组（3.85±0.44%）,1ATA-60min组（5.45±0.52%）,3ATA-30min组（6.08±0.57%）,2ATA-30min组（6.72±0.76%）,3ATA-60min组（7.89±0.62%）,2ATA-60min（9.17±0.50%）;除1ATA-30min组外,其余各HBO组与对照组比较,差异有统计学意义（P<0.01）;同一压力下60min组与30min组之间的差异及2ATA-60min组与其他各组之间的差异均有统计学意义（P<0.01）。结论：2 ATA压力下稳压时间为60 min的HBO促进NSCs向神经元分化的作用最强。［中国当代儿科杂志,2010,12（5）：368-372］     

1,25-(OH)2D3抑制脂多糖诱导的脐血CD4+T细胞IL-13和IL-17的表达

目的 本研究旨在探讨生命早期脂多糖(LPS)对脐血CD4+T细胞白介素-13(IL-13)和白介素-17(IL-17)表达的影响及1,25-(OH)2D3对其表达的干预作用,为维生素D的临床合理应用及其对哮喘等变态反应性疾病的防治提供理论依据。方法 选取顺产的足月新生儿12例,断脐后立即取胎盘端脐静脉血50 mL,采用密度梯度离心法分离脐血单个核细胞(CBMCs),磁珠分选CD4+T细胞后依据不同的处理方法分为空白刺激组、LPS(10 μg/mL)单独刺激组和LPS(10 μg/mL)+1,25-(OH)2D3(10-8 mmol/L)共刺激组。培养72 h后采用双抗夹心酶联免疫吸附试验(ELISA)和Real-Time PCR分别检测培养上清液中IL-13和IL-17水平及CD4+T细胞中IL-13和IL-17 mRNA表达。结果 与空白刺激组相比,LPS单独刺激组培养上清液中IL-13和IL-17水平及CD4+T细胞中IL-13和IL-17 mRNA表达水平明显升高(均P<0.01),而1,25-(OH)2D3处理可降低其表达水平(均P<0.05),但仍高于空白刺激组(均P<0.01)。结论 LPS可促进脐血CD4+T细胞IL-13和IL-17的表达;1,25-(OH)2D3对于LPS诱导的脐血CD4+T细胞IL-13和IL-17表达具有抑制作用,提示1,25-(OH)2D3可能在变应原致敏的早期发挥一定保护作用。     

脐血25羟基维生素D3对早期婴儿特应性皮炎的预测作用

目的 探讨脐血25羟基维生素D3[25（OH）D3]对婴儿特应性皮炎的预测价值，为婴儿早期特应性皮炎的一级预防提供参考指征。方法 选择2015年7~9月期间出生的新生儿，于生后立即采集脐血并检测脐血25（OH）D3水平。所有婴儿分别于生后6周、3个月、6个月时进行门诊随访，记录特应性皮炎的发生情况。结果 最终有67例婴儿全部完成了为期6个月的随访过程，纳入本研究。有23例（34%）出现特应性皮炎，其中91%（21/23）的婴儿特应性皮炎出现在生后的第1个月。根据特应性皮炎的发生情况将婴儿分为特应性皮炎组（n=23）和健康对照组（n=44），特应性皮炎组脐血25（OH）D3水平低于正常组（P < 0.05）。根据脐血25（OH）D3水平分为 < 30 nmol/L（n=21）和 ≥ 30 nmol/L组（n=46），<30 nmol/L组婴儿特应性皮炎发病率高于 ≥ 30 nmol/L组（P < 0.05）。ROC分析结果显示：曲线下面积（AUC）为0.648，标准误为0.075，95%CI为0.502~0.795，灵敏度为52.2%，特异度为79.5%，阳性预测值为57.1%，阴性预测值为76.1%，故脐血25（OH）D3对AD的诊断价值较低。Logistic回归分析结果显示：低脐血25（OH）D3水平、母孕期喜食海鲜、特应性家族史阳性、混合喂养4个因素是影响特应性皮炎发生的危险因素（P < 0.05）。结论 脐血25（OH）D3水平与特应性皮炎的发病风险呈现负性相关关系，但是对特应性皮炎的诊断价值较低。     

人参皂甙对人白血病-60细胞凋亡的影响

目的：探讨人参皂甙对白血病细胞的致凋亡作用及其相关作用机制。方法：采用MTT细胞毒实验检测不同浓度（100、50、25、12.5、6.25、3.125、1.5625 μmol/L）人参皂甙对人白血病-60（HL-60）细胞的生长抑制活性;流式细胞术Annexin V/PI双染法检测不同浓度（0、5、10、20 μmol/L）人参皂甙诱导HL-60细胞凋亡情况;提取各种浓度人参皂甙处理的细胞总蛋白,Western blot检测caspase-8、caspase-9和caspase-3裂解情况;Western blot检测10 μmol/L人参皂甙处理HL-60细胞后caspase-8和caspase-9 抑制剂对caspase-3 裂解情况的影响。结果：人参皂甙对白血病HL-60细胞具有高效的细胞毒作用,IC50值为7.3±1.2 μmol/L;0、5、10、20 μmol/L 人参皂甙处理HL-60细胞48 h后,流式细胞仪检测细胞的凋亡率呈剂量依赖性,各处理组之间差异有统计学意义（F=12.67,P<0.01）;Western blot检测细胞中caspase-9和caspase-3出现裂解带,而caspase-8未出现裂解带;10 μmol/L人参皂甙诱导caspase-3裂解可以被caspase-9的特异性抑制剂Z-LEHD-FMK所抑制,而caspase-8的特异性抑制剂Z-IETD-FMK却没有这一作用。结论：人参皂甙对人白血病HL-60细胞具有高效的致凋亡作用,激活线粒体凋亡途径可能是其致凋亡的主要作用机制。     

1,25(OH)2D3对载脂蛋白E缺乏鼠主动脉内皮细胞增生与凋亡及一氧化氮合酶表达的影响

目的 了解1,25(OH)2D3对载脂蛋白E缺乏鼠(apoE-/-)主动脉内皮细胞(EC)增生、凋亡及内皮型一氧化氮合酶(eNOS)表达的影响.方法 apoE-/-鼠主动脉EC分离培养,MTT法观察1,25(OH)2D3影响apoE-/-鼠EC生长,TUNEL检测细胞凋亡,RT-PCR检测Bc1-2、Fas mRNA和eNOS mRNA表达.结果 细胞对照组与无水乙醇对照组EC增生率差异无统计学意义[(0.162±0.031)vs.(0.158±0.006),p＞0.05],1,25(OH)2D3在10-4、10-5、10-6、10-7、10-8 mol/L时EC增生率高于对照组(P＜0.01),但不同浓度1,25( OH)2D3作用组之间差异无统计学意义[分别为(0.189±0.013)、(0.285±0.011)、(0.296±0.026)、(0.284±0.017)、(0.233±0.010),P ＞0.05],选定10-6mol/L 1,25(OH)2D3为研究浓度,干预分离培养apoE-/-鼠主动脉EC.1,25( OH)2D310-6mol/L组、细胞对照组、无水乙醇对照组凋亡指数分别为(15.14±3.19)、(18.94 ±4.22)、(19.27±4.58),Bcl-2 mRNA分别为(0.78±0.16)、(0.46±0.21)、(0.42±0.17),Fas mRNA分别为(0.43±0.12)、(0.79±0.21)、(0.81±0.20),eNOS mRNA分别为(0.56±0.16)、(0.39±0.13)、(0.35±0.11).25(OH)2D3干预组EC凋亡指数、Fas mRNA、eNOS mRNA降低,Bcl-2 mRNA增高(P均＜0.01),细胞对照组与无水乙醇对照组比较差异无统计学意义(P＞0.05).相关分析发现在1,25(OH)2D3干预组,eNOS表达量与凋亡指数、Fas mRNA呈负相关(r=-0.676、-0.758),与Bcl-2表达呈正相关(r =0.762),差异有统计学意义(P均＜0.01).结论 1,25(OH)2D3刺激apoE-/-鼠主动脉EC增生、抑制主动脉EC凋亡,影响凋亡相关基因Bcl-2、Fas mRNA表达,上调eNOS mRNA表达.     

邻苯二甲酸正丁酯对HL-60细胞凋亡影响及其作用机制

目的探讨邻苯二甲酸正丁酯(DBP)对急性早幼粒细胞性白血病细胞系HL-60细胞增殖和凋亡的影响及其作用机制。方法用细胞形态学观察、DNA断裂百分率及DNA片段凝胶电泳法观察DBP对HL-60细胞增殖与凋亡的影响,用Fu-ra-2AM方法检测对HL-60细胞内游离钙离子浓度的影响,用免疫组织化学方法检测对细胞c-myc和bcl-2蛋白表达的影响。结果DBP可剂量和时间依赖性地抑制HL-60细胞增殖,并诱导其凋亡;引起HL-60细胞内钙重新分布,促进细胞外钙离子内流,升高细胞内游离钙([Ca2 ]i);下调白血病细胞c-myc和bcl-2蛋白表达。结论DBP可能通过提升HL-60白血病细胞内钙离子水平启动凋亡,且下调c-myc和bcl-2蛋白表达促进细胞凋亡,从而发挥其净化HL-60细胞的作用。     

Calcium transport by plasma membranes of enterocytes during development: role of 1,25-(OH)2 vitamin D3

Calcium transport across the intestinal enterocytes represents an entry process at the brush border membranes and an ATP-dependent exit process located at the basolateral membranes. Both processes exhibit developmental changes. The present studies were designed to define the role of vitamin D in calcium transport during maturation. Brush border and basolateral membranes from vitamin D-deficient suckling and adolescent rats were used to study calcium entry and exit. 1,25-(OH)2 vitamin D3 administration enhanced calcium entry at the brush border membranes of suckling and adolescent rats. The increase in calcium uptake in both age groups was secondary to an increase in maximal transport capacity (Vmax) rather than in Km. In suckling rat brush border membranes, 1,25-(OH)2 vitamin D3 treatment increased the Vmax from 1.0 +/- 0.1 to 1.8 +/- 0.2 nmol/mg protein/7 s (p less than 0.01), whereas in adolescent rats, Vmax increased from 1.5 +/- 0.1 to 2.5 +/- 0.3 nmol/mg protein/7 s (p less than 0.01). Km values were not altered. Similarly, 1,25-(OH)2 vitamin D3 administration enhanced ATP-dependent calcium exit at the basolateral membranes of both suckling and adolescent rats. Vmax of ATP-dependent calcium uptake by basolateral membranes of suckling rats increased from 0.5 +/- 0.05 to 0.81 +/- 0.06 nmol/mg protein/20 s (p less than 0.01) whereas in adolescent rats, Vmax increased from 0.3 +/- 0.03 to 0.6 +/- 0.04 nmol/mg protein/20 s (p less than 0.001). Km values were not altered. The current studies indicate that 1,25-(OH)2 vitamin D3 stimulates calcium entry and exit across the enterocytes during maturation.     

Parenteral nutrition for infants: effect of high versus low calcium and phosphorus content

Calcium (Ca) and phosphorus (P) homeostasis were determined in 18 infants (birth weight, 2,810 +/- 135 g; gestational age, 37.4 +/- 0.5 weeks; mean +/- SEM) who received high or low Ca and P content (Ca, P) parenteral nutrition (PN) with a fixed, low dose of vitamin D (25 IU/dl). Nine infants were randomized into low (standard) Ca, P (20 mg Ca and 15.5 mg P/dl) and nine into high Ca, P (60-80 mg Ca and 46.5-62 mg P/dl) PN, and then were studied for up to 6 weeks. The high Ca, P group had stable serum 1,25 dihydroxyvitamin D [1,25(OH)2D], which consistently remained within the normal range (less than 116 pg/ml). Tubular reabsorption of phosphorus (TRP) also was stable and remained consistently less than 90%. The low Ca, P group had elevated and higher 1,25(OH)2D (p = 0.03) than the high Ca, P group. The mean serum 1,25(OH)2D concentration rose from 32 to 112, 115, and 133 pg/ml over a period of 6 weeks. TRP also was higher (p = 0.02) and remained consistently greater than 90%. There were no significant differences between groups in serum parathyroid hormone, calcitonin, Ca, Mg, P, alkaline phosphatase, vitamin D binding protein, and 25 hydroxyvitamin D concentrations; urine Ca/creatinine and Mg/creatinine ratios, and fractional excretion of sodium (Na). Thus, a "high" Ca (60 mg/dl) and P (46.5 mg/dl) content in PN solutions can result in stable serum 1,25(OH)2D and TRP, presumably reflecting minimal stress to Ca and P homeostatic mechanisms without further increase in urinary Ca excretion.     

Specific 1,25-hydroxycholecalciferol receptors and stimulation of 25-hydroxycholecalciferol-24R hydroxylase in human amniotic cells

We have analyzed the 1 alpha, 25-dihydroxycholecalciferol [1,25(OH)2D3] receptor content of cultured cells from human amniotic fluid. Six cell lines were grown to confluence in a minimum essential medium containing 20% fetal calf serum. All had a normal karyotype, five were male and one was female. Hypertonic cytosol extracts were prepared by sonication followed by centrifugation at 200,000 X g 30 min. Saturation analysis was performed by incubating the extracts with [3H]-1,25(OH)2D3 (20-500 pM, 160 Ci/mmol) with and without 100-fold molar excess of unlabeled 1,25(OH)2D3. Linear sucrose gradient (5-20% w/v) analysis was performed with 1.5 nM [3H]-1,25(OH)2D3 alone or in presence of 100-fold molar excess, 1,25(OH)2D3. Functional responsiveness was measured by induction of 25-hydroxycholecalciferol-24R-hydroxylase with 1 and 10 nM 1,25(OH)2D3. The six cell lines studied had receptors with dissociation constant of 44 +/- 6 pM (mean +/- SEM). The binding capacity was 10,200 +/- 1,750 sites/ng protein (mean +/- SEM) with extreme values of 4,700 and 15,500. A single peak for specific binding migrating at approximately 3S was observed by sucrose gradient centrifugation. 25-Hydroxycholecalciferol-24R-hydroxylase was induced by 1 and 10 nM 1,25(OH)2D3 in a dose-dependent fashion. The data show that receptors for 1,25(OH)2D3 are present in cultured amniotic fibroblast-like cells early in pregnancy. These cells may thus prove to be useful for further characterization of 1,25(OH)2D3 receptors in fetal tissue.     

Determination of the production and metabolic clearance rates of 1,25-dihydroxyvitamin D3 in the pregnant sheep and its chronically catheterized fetus by primed infusion technique

Because little is known regarding the determinants of plasma 1,25-dihydroxyvitamin D3(1,25(OH)2D3), or its fate in the fetus, we used a primed infusion technique, using physiologic amounts of high specific activity 3H-1,25(OH)2D3 to study the in vivo production rate (PR) and metabolic clearance rate (MCR) of 1,25(OH)2D3 in chronically catheterized maternal and fetal sheep during the last month of gestation (term = 145 d). The fetal MCR of 1,25(OH)2D3 was calculated at steady state, achieved within 2 h, and was found to be 2.53 +/- 0.19 mL/min (mean +/- SEM) compared to the maternal value of 15.9 +/- 0.94 mL/min. When expressed on a body wt basis, the fetal MCR of 1.22 +/- 0.09 mL/min/kg was more than 4-fold higher than the corresponding maternal value of 0.27 +/- 0.02 mL/min/kg. Measurement of endogenous plasma 1,25(OH)2D3 by RIA revealed mean fetal values of 89 +/- 10 pg/mL compared to the maternal value of 65 +/- 9 pg/mL. Fetal daily PR of 0.33 +/- 0.024 micrograms/d was 22% of the maternal PR of 1.49 +/- 0.11 micrograms/d. However, calculation of PR on a body wt basis revealed a fetal value of 0.159 +/- 0.012 micrograms/d/kg that was more than 6-fold higher than the maternal value of 0.025 +/- 0.002 micrograms/d/kg. Thus, fetal plasma concentrations of 1,25(OH)2D3 are sustained in the face of a high clearance rate of the hormone. The high MCR may be related to the high in vivo circulating concentrations of 1,25(OH)2D3, fetal to maternal placental transfer or target tissue uptake. In view of the high turnover of 1,25(OH)2D3, we suggest that this hormone has a biologic importance that warrants further investigation.     

High total and free 1,25-dihydroxyvitamin D concentrations in serum of premature infants

We investigated the relationship between serum total and free 1,25-dihydroxyvitamin D (1,25-OH2D) and the biochemical regulation of 1,25-OH2D production in premature infants. We measured 1,25-OH2D, vitamin D binding protein and related biochemical parameters and calculated the free 1,25-OH2D index in serum of 17 premature infants (birthweight 810-1700 g; gestational age 31-36 weeks) on two different occasions defined by body weight (Study A: 1,750-1,850 g, Study B: 2,100-2,200 g). Dietary calcium (Ca) intake was 1,5 or 2,6 mmol/kg/d, phosphorus (P) intake 1,7 mmol/kg/d and vitamin D intake 1,000 IU/d. Biochemical results were similar in infants with different Ca intakes and all were within reference ranges. Concentrations of vitamin D binding protein (Study A 0.15 +/- 0.03 g/l, Study B 0.14 +/- 0.03 g/l; means +/- SD) were lower, concentrations of 1,25 (OH)2D (Study A 180 +/- 67 pmol/l, Study B 216 +/- 53 pmol/l) were higher, and consequently the free 1,25-OH2D index (Study A 6.6 +/- 2.7, Study B 8.8 +/- 2.6) was 4 to 6 times higher than in previously studied term infants. 1,25-OH2D and the free 1,25-OH2D index increased significantly with age and were not correlated with serum P or parathyroid hormone. The data indicate that in premature infants with normal biochemical parameters of Ca and P metabolism elevated concentrations of 1,25-OH2D signify an increased fraction of free 1,25-OH2D and that increased production of 1,25-OH2D is not due to hypophosphatemia or hyperparathyroidism.     

Early response to vitamin D2 in children with calcium deficiency rickets

OBJECTIVE: To assess the effect of vitamin D(2) administration on serum vitamin D metabolite concentrations in calcium deficiency rickets. STUDY DESIGN: We administered vitamin D(2), 50,000 IU orally to 16 Nigerian children 15 to 48 months of age with radiographically active rickets. We measured calcium and vitamin D metabolites at baseline and at 1, 3, 7, and 14 days. RESULTS: At baseline, ranges of serum 25-hydroxyvitamin D (25(OH)D) concentrations were 18 to 40 nmol/L (7-16 ng/mL), and 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) concentrations were 290 to 790 pmol/L (120-330 pg/mL). After vitamin D administration, serum 25(OH)D and 1,25(OH)(2)D concentrations rapidly rose and peaked at 2.8 and 1.9 times the baseline values (P < .001), respectively, at 3 days. Positive correlations between 1,25(OH)(2)D and 25(OH)D were strongest at day 3 (r = 0.84, P < .001) and weakest at day 14 (r = 0.41, P = .11). The relationship of 1,25(OH)(2)D with 25(OH)D at baseline and the increase in 1,25(OH)(2)D in response to vitamin D were similar to those described in children with vitamin D deficiency. However, unlike the pattern in vitamin D deficiency, 1,25(OH)(2)D remained positively correlated with 25(OH)D after administration of vitamin D. CONCLUSION: Dietary calcium deficiency increases the demand for 25(OH)D above that required in vitamin D deficiency to optimize 1,25(OH)(2)D concentrations. Assessment of vitamin D sufficiency in persons or communities may need to be adjusted for habitual dietary calcium intake.     

Pregnancy in mice lacking the vitamin D receptor: normal maternal skeletal response,but fetal hypomineralization rescued by maternal calcium supplementation

Fetal mineralization appears to be driven by the pregnancy-induced stimulation of intestinal Ca absorption. We thus hypothesized that mineralization would be impaired in fetuses of mice that lack the vitamin D receptor (VDR). Here we report on the maternal response to pregnancy, and the fetal mineralization, in mice with a homozygous disruption of the VDR gene (VDR-/-) mated with wild-type (wt) males. We found that VDR-/- mice show mild hypocalcemia, clear rickets and osteomalacia on bone histomorphometry, lower cortical bone density on quantitative tomography, and reduced concentrations of calbindin-D9k (CaBP-D9k) in duodenal mucosa and kidney. The skeletal response to pregnancy was comparable in wt and VDR-/- mice; duodenal CaBP-D9k concentrations increased during pregnancy in VDR-/- as in wt mice, but remained 40% lower than in wt mice. We confirmed our hypothesis that mineralization is defective in d18.5 VDR+/- fetuses of VDR-/- mice, both by whole-body Ca determination and histomorphometric evaluation; the number of osteoclastic cells in bone was increased. The fetuses were hypercalcemic and had a 5-fold increase in circulating 1,25(OH)2D3. We then studied pregnancies in VDR-/- females, mated with wt males, fed a high Ca/P/lactose rescue diet during pregnancy. The rescue diet normalized the mineralization, the number of osteoclastic cells, and plasma Ca and 1,25(OH)2D3 concentrations in the fetuses. We interpret the data as evidence that, to ensure normal fetal mineralization, the maternal VDR-dependent intestinal Ca absorption can be substituted by passive Ca absorption entrained by a higher Ca intake. Alternatively or additionally, elevated 1,25(OH)2D3 in utero may disturb bone development.     

Vitamin D metabolite levels in normal children

Vitamin D metabolite levels were measured in 174 normal children throughout the year. 25-hydroxyvitamin D3 (25(OH)D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) levels showed a seasonal variation; both levels were higher in summer than in winter (p less than 0.001 for both). There was a fall in the 1,25-dihydroxyvitamin D (1,25(OH)2D) level in August and September (p less than 0.001), which coincided with a rise in mean 25(OH)D3 and 24,25(OH)2D3 levels. An inverse correlation was seen between 1,25(OH)2D and 24,25(OH)2D3 levels (r = -0.233; p less than 0.01). 25(OH)D3 levels increased with age only for winter values (less than 3 years, 11.70 +/- 3.98 ng/ml; 3-11 years, 18.38 +/- 1.65 ng/ml; greater than 11 years, 23.60 +/- 4.60 ng/ml) while 1,25(OH)2D and 24,25(OH)2D3 levels did not show an age-related difference. Intake of multivitamins had an interesting effect on 25(OH)D3 and 24,25(OH)2D3 levels in the winter but not in the summer; the endogenous metabolite levels were lower in the vitamin supplemented children [25(OH)D3: 23.05 +/- 7.35 versus 15.77 +/- 5.51 ng/ml, p less than 0.001; 24,25(OH)2D3: 2.30 +/- 1.11 versus 1.66 +/- 0.88 ng/ml, p less than 0.05]. Children studied in the winter who were not receiving supplemental vitamins were older than those who did receive the vitamins (7.26 +/- 2.64 versus 5.42 +/- 3.17 years; p less than 0.01). Sixteen of the children had both winter and summer measurements. Their 25(OH)D3 and 24,25(OH)2D3 levels showed the same seasonal variation as the overall group data, while their 1,25(OH)2D levels showed no consistent pattern.(ABSTRACT TRUNCATED AT 250 WORDS)     

新生猪多器官功能障碍综合征模型建立的实验研究

目的：探讨采用盲肠结扎加穿孔(CLP)建立新生猪多器官功能障碍综合征(MODS)模型的方法及实验与临床意义。方法：选用健康长白新生猪14只,随机分成实验组(E组,n=9)和对照组(C组,n=5),实验组施行盲肠结扎加穿孔(CLP)制成MODS动物模型,对照组只行剖腹和盲肠探查术。动态观察两组血清生化指标(ALT,AST,ALB,BUN,Cr,CKMB,lac)及血小板、血气分析(PaO2,PaCO2)的变化,通过光镜观察动物各重要生命器官组织形态学变化。结果：与对照组相比,实验组动物在CLP后血ALT,AST,BUN,Cr,CKMB,lac24h即已开始升高,48～96h明显升高,48h时ALT为83.0±9.3U/L、AST为348.8±132.9U/L、BUN为10.5±2.5mmol/L、Cr为79.2±9.0μmol/L、CKMB为5152.0±1857.8U/L、lac为12.3±4.0mmol/L(P<0.01),96h后开始有所降低,但仍高于0h;ALB24h后开始降低,各时间点均低于对照组,但差异无显著性;血小板24h开始降低,96h与0h比较差异有显著性;PaO2和PaCO248h时实验组与对照组差异有非常显著性(P<0.01);实验组动物死亡率与对照组差异有显著性(P<0.05),MODS的发生率为56%。实验组动物肺、肝、心、肾、胃肠道等器官均有不同程度的病理改变。结论：CLP诱发了新生猪多个器官的功能障碍,该实验可用于新生动物MODS模型的探讨。