去卵巢骨质疏松模鼠DPD及1,25-(OH)2D3与骨质量的相关性研究

目的：探讨雌性SD大鼠切除卵巢后机体尿DPD及血1，25-（0H）2D3变化与骨质量的相关性。方法：40X雌性SD大鼠随机分为卵巢切除组（OVX组）和假手术组（Sham组），分别于术后12、24周取材。运用双能X线骨密度仪测L1、股骨、股骨颈骨密度，ELISA法测尿DPD浓度，激素放免法测血1，25-（OH）2D3浓度，光测弹性仪测L1压缩强度极限、弹性模量及右侧股骨弯曲破坏栽荷，不脱钙骨切片技术观察胫骨上段骨组织形态结构并计量分析，对实验数据进行相关性分析。结果：术后OVX组除尿DPD／Cr明显升高外，其他检测指标均较Sham组低，且随术后时间推移持续下降，差异有统计学意义。相关分析显示：尿DPD／Cr与腰椎、股骨密度、椎体压缩强度极限、股骨弯曲破坏荷载和骨小梁面积均呈负相关。血清1，25-（OH）2D3水平与腰椎、股骨、股骨颈密度、骨小梁面积、椎体压缩强度极限和股骨弯曲破坏荷载呈正相关。结论：大鼠卵巢切除后尿DPD、血1，25-（0H）2D3水平变化与骨质量显著相关，可以通过检测尿DPD、血1，25-（0H）2D，水平变化预测骨质量。     

维生素D衍生物联合供者骨髓细胞输注诱导异基因大鼠心脏移植免疫耐受

目的 探讨同种异基因心脏移植后免疫耐受的诱导。方法 建立大鼠颈部异位心脏移植模型，按分组分别给予门静脉输注供者骨髓细胞(DBMC)(B组)、骨化三醇灌胃(C组)、输注DBMC及骨化三醇灌胃(D组)以及环孢素A(CsA)灌胃(E组)。观察移植心脏的存活时间及心肌组织病理改变，测定心肌组织中肿瘤坏死因子及细胞间粘附分子-1 mRNA的表达以及血清钙、磷浓度，进行受者与供者及无关第三品系大鼠脾细胞混合淋巴细胞培养(MLR)。结果 D组移植心脏的存活时间较其它各组显著延长(P＜0．05)；术后7d，C组、D组、E组受者脾细胞均能显著抑制供者及第三方无关供者脾细胞作为刺激细胞引起的MLR；D组手术前后血磷、血钙浓度的差异无显著性(P＞0．05)；各组急性排斥反应的程度，D组最轻；D组肿瘤坏死因子及细胞间粘附分子-1 mRNA的表达受到显著抑制，与对照组(A组)、B、C组比较，差异有显著性(P＜0．05)。结论 骨化三醇灌胃联合DBMC输注可显著延长移植心脏的存活时间，二者具有协同作用。     

X-linked hypophosphatemia: Normal renal function despite medullary nephrocalcinosis 25 years after transient vitamin D2-induced renal azotemia

Nephrocalcinosis (NC) detected by ultrasound is a recognized abnormality for some patients with X-linked hypophosphatemia (XLH) who received vitamin D₂ and inorganic phosphate therapy, but is commonly observed in XLH patients treated with 1,25-dihydroxyvitamin D₃ and inorganic phosphate supplementation. Nevertheless, long-term follow-up of kidney function in XLH patients with NC detected ultrasonographically has not been reported. We investigated two women with XLH, ages 31 (patient 1) and 39 (patient 2) years, each of whom had suffered at least one documented episode of vitamin D₂-induced hypercalcemia and renal azotemia during childhood. Patient 2 had also been treated with inorganic phosphate. No medications for XLH had been taken during adulthood. Renal ultrasonography at our institution demonstrated marked bilateral medullary NC in both women. No other explanation was found for their NC that apparently occurred several decades earlier from medical therapy for XLH. Detailed studies (including creatinine clearance, β₂-microglobulin excretion, and fasting urinary osmolality and acidification) revealed no impairment of kidney function in either patient. Our findings indicate that subradiographic medullary NC acquired during medical therapy for XLH may persist for decades, but with no adverse renal sequelae. Definitive (long-term) assessment of kidney function in the XLH population with NC, however, will be necessary to fully understand the risk of current medical treatment for this most common heritable form of rickets.     

Circulating 1,25-Dihydroxycholecalciferol After Intravenous Injections of l{alpha}-Hydroxycholecalciferol in Patients on Regular Haemodialysis

The formation of 1.25-dihydroxycholecalciferol (1.25-(OH)₂D₃after single intravenous injections of 1-hydroxycholecalciferol(1-OHD₃) was examined in four patients with chronic renal failureon regular haemodialysis. Following 1–3µg 1-OHD₃administered at weekly intervals, 1.25-(OH)₂D₃ appeared in thecirculation within 1 h, and peak concentrations were reachedbetween 2 h and 5 h. By 8 h serum 1.25-(OH)₂D₃ concentrationshad started declining and by 44 h they had returned to baselineafter 1µg 1-OHD₃ but they were still above basal after2 and 3 µg by an average of 30 pmol/l. One week afterinjections, concentrations were back to basal in all patientsstudied. The serum 1,25-(OH)₂D₃ dose response to injected la-OHDwas linear, indicating ample capacity of the liver 25-hydroxylaseto further hydroxylate 1-OHD. However, examination of the individualresponses revealed lower increments in serum 1.25-(OH)₃ concentrationsin the patients with the highest basal serum 25-hydroxyvitaminD concen trations. Intravenous 1-OHD₃ may be useful in the furtherstudy of the interactions between 1.25-(OH)₂₃ calcium and PTHin chronic renal failure, as well as of the hepatic metabolismof vitamin D.     

Calcitriol oral pulse therapy in children with renal osteodystrophy

A 6-month protocol of oral pulse calcitriol was used in nine uraemic children (2–14 years old) on dialysis who presented with renal osteodystrophy. Calcitriol was administered twice a week, 4 g per dose for patients over 30 kg and 3g for patients less than 30 kg. Plasma levels of parathyroid hormone, calcium, phosphorus and alkaline phosphatase were carefully controlled during the study. Parathyroid hormone levels decreased by 68% and 56% by the 2nd and 6th months of treatment in seven patients, while they remained unchanged in two patients with focal segmental glomerulosclerosis and massive proteinuria. Eight hypercalcaemic episodes from 77 determinations were observed, all of them recovered after 1 week of vitamin D withdrawal. We conclude that oral calcitriol pulse therapy is a good alternative for renal osteodystrophy in uraemic children. Careful monitoring of plasma parathyroid hormone and calcium is needed during follow-up when using this approach in paediatric patients.     

Evidence for vitamin D-independent active calcium absorption in newborn piglets

Summary The role of 1,25-dihydroxycholecalciferol (calcitriol) for intestinal calcium (Ca²⁺) absorption was studied in newborn (<1 week old) and weaned piglets (>6 weeks old). In both groups, normal piglets and piglets suffering from inherited pseudo vitamin D-deficiency rickets, type I (PVDRI) were used. In this inherited disorder, renal production of calcitriol is absent. Plasma samples were assayed for calcitriol and total Ca, and dissociation constants (K_d) and maximum binding capacities (B_max) of intestinal calcitriol receptors were determined under equilibrium conditions at 4°C. Unidirectional Ca²⁺-flux rates were measured across stripped duodenal mucosae in Ussing chambers in the absence of electrochemical gradients. The plasma calcitriol concentrations of neonatal (26.5±7.1 pg/ml, n=11; ± SEM) and weaned PVDRI piglets (18.8±5.7 pg/ml, n=8)were unphysiologically low and differed significantly from control animals (83.6±14.8 pg/ml, n=8, and 86.9±9.6 pg/ml, n=11, respectively). However, newborn PVDRI piglets had normal plasma Ca levels at least during the first days of life. They became hypocalcemic and developed clinical symptoms of rickets during the following weeks. In newborn PVDRI and control piglets, B_max was significantly lower (84±28 fmol/mg protein and 127±55 fmol/mg protein, n=9, respectively) than in weaned piglets (741±82 fmol/mg protein, n=9, and 778±121 fmol/mg protein, n=8, respectively). Significant net Ca²⁺-fluxes were found in both newborn PVDRI and control piglets (88.8±25.1 nmol · cm^-2 · h^-1, n=6, and 86.5±10.5 nmol · cm⁻² · h⁻¹,n=9, respectively). However, active net Ca²⁺ absorption was completely absent in weaned PVDRI piglets. These results indicate the presence of vitamin D-independent mechanisms for active intestinal Ca²⁺ absorption during early postnatal life in pigs.     

骨化三醇治疗慢性肾功能不全患者肾性骨病的效果观察

目的研究慢性肾功能不全患者肾性骨病应用骨化三醇治疗的临床疗效,并分析其安全性。方法选择2014年7月~2016年11月期间所收治的68例肾性骨病患者作为本次研究病例,对患者进行分组治疗,采用随机数字表法进行分组,对照组和研究组各34例,对照组患者应用常规治疗方法,研究组在此基础上加用骨化三醇治疗,对比分析两组患者的临床各项指标,并分析其不良反应发生情况。结果治疗前,两组临床指标无明显统计学意义(P0.05),经治疗后,研究组患者的血清钙水平为(2.31±0.15)mmol/L,血清无机磷水平为(1.89±0.14)mmol/L,甲状旁腺激素为(202.01±35.87)pg/m L,碱性磷酸酶为(80.46±2.85)U/L,其中血清钙、血清无机磷与甲状旁腺激素水平与对照组比较具有统计学意义(t=4.1607、3.1260、5.7254,P0.05),碱性磷酸酶与治疗前比较无统计学意义(t=1.3055,P0.05);研究组患者不良反应发生率为8.82%(3例),对照组患者不良反应发生率为14.71%(5例),两组患者不良反应比较无统计学意义(χ~2=0.5667,P0.05)。结论慢性肾功能不全患者肾性骨病中应用骨化三醇治疗的效果明显,能够有效改善患者的临床症状,改善钙磷紊乱情况,并且不良反应少,可以在临床中推广使用。     

Theoretical basis of a beneficial role for vitamin D in viral hepatitis

Abnormal bone metabolism and dysfunction of the calcium-parathyroid hormone-vitamin D axis have been reported in patients with viral hepatitis. Some studies suggested a relationship between vitamin D and viral hepatitis. Genetic studies have provided an opportunity to identify the proteins that link vitamin D to the pathology of viral hepatitis (i.e., the major histocompatibility complex class Ⅱ molecules, the vitamin D receptor, cytochrome P 450 , the renin-angiotensin system, apolipoprotein E, liver X receptor, toll-like receptor, and the proteins regulated by the Sp1 promoter gene). Vitamin D also exerts its effects on viral hepatitis via non-genomic factors, i.e., matrix metalloproteinase, endothelial vascular growth factor, prostaglandins, cyclooxygenase-2, and oxidative stress. In conclusion, vitamin D could have a beneficial role in viral hepatitis. Calcitriol is best used for viral hepatitis because it is the active form of the vitamin D 3 metabolite.     

钙剂联合骨化三醇治疗绝经后妇女骨质疏松的临床分析

目的:探讨钙剂联合骨化三醇治疗绝经后妇女骨质疏松的临床疗效。方法:回顾性分析2009年5月至2011年4月广东省揭阳市妇幼保健院收治的68例绝经后妇女骨质疏松患者的临床资料。对照组(34例)服用钙尔奇D,观察组(34例)服用钙尔奇D+骨化三醇,共6~12个月。监测治疗前后骨密度(BMD)、骨钙素(BGP)、血清IL-6、TNF-a变化情况。结果:对照组腰椎侧位(L2-4)BMD、血清BGP、IL-6、TNF-a治疗前后差异无统计学意义(P>0.05);治疗后,观察组腰椎侧位(L2-4)BMD、血清BGP较治疗前明显增加(P<0.01)。观察组治疗后血清IL-6、TNF-a浓度均较治疗前降低(P<0.05)。结论:钙剂联合骨化三醇治疗绝经后妇女骨质疏松疗效肯定,可提高骨BMD、BGD,降低血清IL-6、TNF-a浓度。