难复性寰枢脱位的影像学表现与前方减压术式选择初探

目的：研究难复性寰枢脱位的影像学特征,探讨延、脊髓前方减压术式的选择。方法：回顾性分析了36例难复性寰枢脱位患者颅颈区X光片、CT和MRI,其中27例作了经后外侧入路前方减压术。结果：23例为枢椎完整型寰枢脱位,其寰椎侧块前移,有3例并寰椎前下旋转,4例并侧方移位,3例单侧关节脱位较严重;21例合并寰椎桃化,其中2例有枕大孔（即枕化的寰椎孔）不规则狭窄,1例有齿突椎体化畸形。13例为齿突不连型寰枢脱位,其中寰椎后脱位1例;寰椎前脱位为半脱位者8例（其中1例为“齿突骨”）,全脱位者4例。术后CT显示,经后外侧入路前方减压的27例中23例骨性减压满意。结论：就前方减压而言,经后外侧入路的治疗有寰椎“旋转”,齿突畸形（如齿突椎体化、“齿突骨”等）或枕大孔不规则狭窄等的寰枢脱位有其优势,经口入路松解并牵引复位治疗齿突不连的寰枢椎全脱位较合理。     

经枕颈后外侧入路齿状突切除治疗寰枢椎陈旧性脱位

目的　为解决难复性寰枢椎陈旧性脱位的外科治疗,探索手术入路措施。方法采用经枕颈后外侧入路切除齿状突并一期行枕颈融合治疗难复性寰枢椎陈旧性脱位5例。结果5 例手术经过顺利,术后神经症状均有明显改善,肌力均有一级以上恢复。无感染及死亡。结论　对难复性寰枢椎陈旧性脱位,尤其是压迫因素来自前方者,经枕颈后外侧入路切除齿状突和颈2 椎体后上份,能同时达到脊髓前、后方彻底减压及一期枕颈融合。此手术入路齿状突显露清楚,手术操作简便、安全。是一种较理想的手术方法。     

后路寰枢椎侧块关节融合器置入的临床应用解剖

目的了解国人寰枢椎侧块关节周围血管、神经的解剖关系,为后路寰枢椎侧块关节融合器准确、安全置入提供解剖学依据。方法选用成人尸体标本20具,冠状面上观察寰枢椎侧块关节后缘周围解剖关系;平枢椎侧块上关节面后缘测量C1、2间椎动脉内缘至颈髓硬脊膜外缘的距离,确定手术冠状位的"安全操作空间";测量枢椎下关节突后内缘的纵垂线与枢椎椎弓上缘交点(G点)至枢椎椎弓根上缘中线延长线的水平距离,确定手术切入点。结果 "安全操作空间"为(19.72±1.84)mm,水平距离为(2.23±0.45)mm。寰枢椎后膜下的静脉丛主要集中在寰枢椎侧块关节的外缘、上方和内缘,其下方尤其枢椎椎弓根上缘的静脉丛稀疏。位于寰椎椎弓根下方、寰枢椎侧块关节内上侧的C2神经根,距颈硬脊膜外缘5~7 mm处膨大成颈神经节,并发出前、后支。结论 G点恒定在枢椎椎弓根上缘中线延长线的内侧2.5 mm处,以此点向外水平旁开2.5 mm,向上推开寰枢后膜,内上骨膜下剥离并沿枢椎椎弓根上缘中线一并剥离枢椎椎弓根骨膜和寰枢椎侧块关节囊,即可显露寰枢椎侧块关节并置入融合器。以此入路在"安全操作空间"内置入融合器,可避免切开寰枢后膜而损伤血管和神经,保证了手术的安全。     

经口咽入路人工寰齿关节置换术的解剖学研究

目的为经口咽入路处理斜坡至上颈椎腹侧病变和人工寰齿关节设计及应用提供解剖学依据。方法对8具新鲜成人头颈部标本经口咽入路进行逐层解剖,观察咽后壁的层次、椎动脉的走行、寰枢椎的解剖毗邻关系和人工寰齿关节置换术的相关解剖参数等。另选32套成人新鲜寰枢椎骨性标本,测量寰椎前弓骨窗宽、枢椎椎体骨窗宽、寰椎部件上位进钉点间距、寰椎部件下位进钉点间距、枢椎部件上位进钉点间距、枢椎部件下位进钉点间距等。结果寰椎和枢椎可显露宽度分别为(40.2±3.5)mm和(39.3±3.7)mm。咽后壁可显露宽度和高度分别为(40.1±5.2)mm和(50.2±4.6)mm。寰椎上位进钉点间距和下位进钉点间距分别为(28.0±2.9)mm和(24.0±3.5)mm,枢椎上位进钉点间距和下位进钉点间距分别为(18.0±3.3)mm和(16.0±3.5)mm。经口咽入路手术可以达到斜坡下缘至C3椎体上缘。咽后壁由浅至深可分五层结构和两个间隙。结论经口咽入路手术处理斜坡下缘到上颈段腹侧病变具有手术路径短、显露好、减压效果肯定等优点。人工寰齿关节的设计可以上述测量数据为依据。     

前路松解复位后路内固定治疗难复性寰枢关节脱位

目的：探讨难复性寰枢关节脱位的手术治疗方法。方法：对3例难复性寰椎前脱位的病例经口咽入路切断颈长肌、头长肌、前纵韧带和寰枢侧块关节囊，施行松解复位术，同期行后方固定植骨融合术。后方固定方法包括：经寰枢侧块关节螺钉固定、寰枢侧块钉板固定和借助于枢椎椎弓根螺钉的枕颈固定。结果：3例均获得了解剖复位和植骨融合。结论：经口咽入路的寰枢关节松解复位术可使难复性脱位的寰枢关节获得充分复位，松解复位术是一种安全、有效的治疗方法。     

难复性寰枢关节脱位的手术治疗

目的探讨难复性寰枢关节脱位的手术治疗方法。方法54例难复性寰枢关节脱位患者,男32例,女22例;年龄7～63岁,平均32岁。其中齿突不连18例,寰椎枕骨化畸形22例,齿突骨折畸形愈合5例,寰椎横韧带松弛9例。40例有脊髓病或脊髓损伤的症状、体征。先行经口咽入路的寰枢关节松解复位术,术中横断挛缩的椎前肌、前纵韧带和侧块关节囊,借助于牵引和器械撬拨的力量使寰枢关节复位;同期行后路寰枢或枕颈固定植骨融合术,后路固定方法包括经寰枢侧块关节螺钉固定5例、寰枢侧块钉板固定12例和借助于枢椎椎弓根螺钉与枕颈固定板的枕颈固定37例。术后不用外固定。结果41例获得解剖复位;13例部分复位,其中2例行部分齿突切除,另11例术前颈髓角平均104.1°,术后120.2°。48例随访4～40个月,平均15.7个月,全部病例均获骨性融合。术前有脊髓症状的38例术后功能评价(Odom标准)为优15例,良14例,可8例,差1例。术中出现硬膜破裂1例,椎弓根钉切割1例;术后出现呼吸衰竭1例,发音不正常3例,吞咽不利1例,术后2周发生败血症脊髓炎致瘫痪1例,术后2个月内固定松动1例。结论经口咽入路寰枢关节松解复位结合后路坚强内固定及植骨融合,对难复性寰枢关节脱位有良好的治疗效果。     

Ⅰ期前后路联合手术治疗游离齿突继发的难复性寰枢椎脱位

目的探讨颈高位咽后入路前路松解、Ⅰ期后路融合治疗游离齿突继发的难复性寰枢椎脱位的临床效果。方法本组19例均为游离齿突继发的难复性寰枢椎脱位,X线片动态位不能自行复位,且术前颅骨牵引均未获得满意复位。采用颈高位咽后入路显露C1～C3,行寰枢椎前方松解复位,Ⅰ期后路寰枢融合内固定。结果 19例患者采用颈高位前方咽后入路均成功显露C1前弓～C3椎体,前路松解后复位良好,Ⅰ期行后路寰枢融合内固定,全组无一例出现脊髓损伤加重、咽喉部阻塞或窒息。1例颈后部伤口积液感染,经换药引流后痊愈;2例出现舌下神经牵拉症状,1例出现面神经刺激症状,均在1个月后恢复正常。脊髓功能正常者无神经功能损害,不全瘫患者神经功能均有部分恢复。随访植骨均获骨性融合,无内固定松脱。结论颈高位咽后入路行前方松解能够复位游离齿突继发的难复性寰枢椎脱位患者,Ⅰ期后路寰枢融合可获良好的植骨融合。     

经枕颈后外侧入路治疗寰枕区腹侧病变的安全性评估

目的 对经枕颈后外侧入路手术治疗寰枕区腹侧病变的不良事件作统计,评估该术式的安全性.方法 1999～2006年,对74例寰枕区以腹侧病变压迫为主的患者进行治疗,手术经枕颈后外侧入路,先行枕骨大孔扩大及寰椎后弓切除减压,再经枕颈区硬脊膜侧方显露齿突及C2椎体做相应压迫因素切除,达到脊髓前后方同时减压,并同期完成枕颈植骨...     

数字骨科技术在寰枢椎手术中的应用 寰枢椎脱位系列讲座(七)

正1概述寰枢椎位于颅脊交界区,解剖结构上具有独特性。寰椎由前后弓、侧块、横突构成,侧块上接枕骨髁、下邻枢椎关节突上关节面,形成寰枢外侧关节,而枢椎齿突与寰椎前弓构成寰齿关节,寰枢、寰枕之间由横韧带、翼状韧带和齿突尖韧带等多个韧带连接,这样就形成了一个复杂的三维复合结构;寰枢椎还毗邻诸多重要的血管和神经,因此治疗难度较大,风险较高[1-2]。寰枢椎脱位是各种上颈椎与颅脊交界疾患的病理转归,临床上并不少见,除了部分儿童自发性     

枕颈后外侧入路齿状突切除治疗寰枕部畸形

目的:探索治疗寰枕部畸形的新的手术入路.方法:采用经枕颈后外侧入路齿状突切除治疗寰枕部畸形4例,一期达到前方、侧方及后方的减压并后路植骨枕颈融合,术后Holo背心头环外固定.结果:本组病例获效满意,无病情加重,无手术死亡及术后感染,术后随访10个月～5年6个月,感觉恢复接近正常,四肢肌力明显增加,肌张力降低,能自己行走.结论:经枕颈后外侧入路行齿状突切除术野清楚、操作简单、减压充分,经枕颈后外侧入路是治疗寰枕部畸形较为理想的手术入路.     

Potent suppression of the parathyroid glands by hydroxylated metabolites of dihydrotachysterol(2).

BACKGROUND: Dihydrotachysterol(2), a licensed pharmaceutical, is hydroxylated to 25-hydroxydihydrotachysterol(2) (25(OH)DHT(2)) and 1 alpha,25-dihydroxydihydrotachysterol(2) (1 alpha,25(OH)(2)DHT(2)) in man. We have compared the biological activity of these metabolites with calcitriol and the 'non-calcaemic' analogue, 22-oxacalcitriol (OCT) in bovine parathyroid cell cultures and in rats. METHODS: The effect of each sterol on parathyroid hormone (PTH) secreted by primary bovine parathyroid cells was measured. High-performance liquid chromotography and gas chromotography-mass spectrometry were used to investigate in vitro 25(OH)DHT(2) metabolism. Rats were given a single intraperitoneal injection or five daily injections of each sterol, and changes in ionized calcium and PTH were measured. RESULTS: In vitro, all sterols suppressed PTH significantly. Calcitriol and OCT were of similar potency, but 1 alpha, 25(OH)(2)DHT(2) and 25(OH)DHT(2) required higher concentrations to suppress PTH equally. We were unable to detect metabolism of 25(OH)DHT(2) to 1 alpha,25(OH)(2)DHT(2) in vitro. In rats, a single dose of 0.5 microg/rat of calcitriol increased ionized calcium at 30 and 40 h (statistically significant at 48 h). 50 microg of OCT and 1 alpha,25(OH)(2)DHT(2) did not cause significant hypercalcaemia at 48 h, although 1 alpha,25(OH)(2)DHT(2) caused hypercalcaemia at 30 h. In contrast, 50 microg of 25(OH)DHT(2) caused hypercalcaemia at 48 h but not at 30 h. Five daily doses of 0.001 microg/rat of calcitriol caused a significant rise in calcium and a 50% fall in PTH. OCT and 1 alpha,25(OH)(2)DHT(2) at 0.025 and 0.5 microg/rat respectively caused similar suppression of PTH but without hypercalcaemia. CONCLUSION: 1 alpha,25(OH)(2)DHT(2) and 25(OH)DHT(2) are potent suppressors of PTH in vitro and in vivo. 25(OH)DHT(2) may be active by virtue of its pseudo-1 alpha-hydroxyl group. Hypercalcaemia caused by a single dose of 1 alpha,25(OH)(2)DHT(2) appeared to be more transient than calcitriol. Five daily doses of 1 alpha, 25(OH)(2)DHT(2) and OCT could achieve 50% suppression of PTH without significant increments in ionized calcium. In contrast, suppression of PTH by calcitriol was associated with significant increments in ionized calcium. These data suggest that like OCT, 1 alpha, 25(OH)(2)DHT(2) can dissociate calcaemic actions from parathyroid-suppressing actions in a manner that may be therapeutically useful.     

枢椎椎弓根螺钉进钉点的解剖定位研究

目的研究枢椎下关节突与枢椎椎弓根的位置关系,建立以枢椎下关节突为解剖标志的枢椎椎弓根螺钉进钉定位技术。方法取50套成人干燥枢椎标本,测量枢椎椎弓根的内、外缘和枢椎下关节突的内缘、中点、外缘分别与正中矢状线的垂直距离,以及枢椎椎弓根的宽度与高度。通过分析测量值间的关系,建立枢椎椎弓根螺钉的进钉定位技术。结果枢椎下关节突内缘在枢椎椎弓根内缘的外侧(3.67±0.41)mm处,枢椎下关节突中点在枢椎椎弓根外缘的外侧(1.15±0.44)mm处。建立了两种以枢椎下关节突为标志的进钉点定位方法,进钉点A位于枢椎下关节突内上象限,即中心点内、上各2mm处;进钉点B位于经枢椎下关节突内缘的纵垂线与枢椎下关节突中上1/4水平线的交点。结论枢椎下关节突与枢椎椎弓根间存在较恒定的解剖位置关系,枢椎下关节突可作为术中判断枢椎椎弓根位置和确定枢椎椎弓根螺钉进钉点的简易解剖学标志。     

Effects of vitamin D compounds on renal and intestinal Ca2+ transport proteins in 25-hydroxyvitamin D3-1alpha-hydroxylase knockout mice

BACKGROUND: Vitamin D compounds are used clinically to control secondary hyperparathyroidism (SHPT) due to renal failure. Newer vitamin D compounds retain the suppressive action of 1,25(OH)(2)D(3) on the parathyroid glands and may have less Ca(2+)-mobilizing activity, offering potentially safer therapies. METHODS: This study investigated the effect of a single dose of compound (1,25(OH)(2)D(3), 1,24(OH)(2)D(2), or 1alpha(OH)D(2)) on renal and intestinal Ca(2+) transport proteins, including TRPV5 and TRPV6, and serum Ca(2+), in a novel SHPT model, the 25-OH-D(3)-1alpha-hydroxylase knockout mouse, which lacks endogenous 1,25(OH)(2)D(3) and is severely hypocalcemic. Animals were injected intraperitoneally with compound (100 ng/mouse). RESULTS: Serum levels of 1,25(OH)(2)D(3) and 1,24(OH)(2)D(2) peaked at four hours post-injection (pi), then declined rapidly. 1,25(OH)(2)D(2) generated from 1alpha(OH)D(2) peaked at 12 hours pi and then remained stable. Serum Ca(2+) was increased to near-normal within four hours by 1,25(OH)(2)D(3) and 1,24(OH)(2)D(2), and within 12 hours by 1alpha(OH)D(2). 1,25(OH)(2)D(3) and 1,24(OH)(2)D(2) up-regulated duodenal TRPV5 and TRPV6 mRNA to a similar degree within four hours; mRNA levels decreased by 12 hours after 1,24(OH)(2)D(2) treatment, and by 24 hours after 1,25(OH)(2)D(3) treatment. 1,25(OH)(2)D(3) increased kidney levels of TRPV5, calbindin-D(28K), and calbindin-D(9K) mRNA within four hours; 1,24(OH)(2)D(2) did not change kidney TRPV5 levels and modestly increased calbindin D(9K) by 48 hours. 1alpha(OH)D(2) produced later-onset effects, increasing duodenal TRPV6 and calbindin-D(9K) mRNA levels by 12 hours and TRPV5 by 48 hours. CONCLUSION: In kidney, 1alpha(OH)D(2) increased TRPV5, calbindin-D(28K), and calbindin-D(9K) mRNA levels by 12 hours. This study indicates that Ca(2+) transport proteins, including TRPV5 and TRPV6, are differentially up-regulated by vitamin D compounds.     

Near-infrared spectroscopy reflects changes in mesenteric and systemic perfusion during abdominal compartment syndrome

BACKGROUND: Continuous and minimally invasive near-infrared spectroscopy (NIRS)-derived gastric tissue oxygen saturation (GStO(2)) and muscle tissue oxygen saturation (MStO(2)) were evaluated in a clinically relevant porcine model of hemorrhagic shock and abdominal compartment syndrome (ACS). METHODS: Phenobarbital-anesthetized swine underwent pulmonary artery catheter insertion for mixed venous oxygen saturation (SvO(2)) measurement and midline laparotomy to permit placement of a gastric NIRS probe, a jejunal (regional carbon dioxide [PrCO(2)]) tonometer, superior mesenteric artery (SMA) flow probe, and a portal vein oxygen saturation (SpvO(2)) catheter. A muscle NIRS probe was placed on the front limb. After randomization, Group 1 underwent hemorrhage and resuscitation. Group 2 had no hemorrhage or resuscitation. ACS was induced by peritoneal fluid infusion in both groups. A significant decrease in SMA flow, SpvO(2), GStO(2), SvO(2), and MStO(2) was observed after hemorrhage in Group 1 and with abdominal hypertension in both groups. RESULTS: GStO(2) significantly correlated with SMA flow (Group 1: r(2) = 0.90; Group 2: r(2) = 0.83) and mesenteric oxygen delivery (mesenteric oxygen delivery, Group 1: r(2) = 0.73; Group 2: r(2) = 0.89). MStO(2) significantly correlated with SvO(2) (Group 1: r(2) = 0.99; Group 2: r(2) = 0.65) and systemic oxygen delivery (SDO2, Group 1: r(2) = 0.60; Group 2: r(2) = 0.88). Tonometer-derived PrCO(2) values did not change at any time point in either group. CONCLUSIONS: NIRS measurement of GStO(2) and MStO(2) reflected changes in mesenteric and systemic perfusion respectively during hemorrhage and ACS.     

Oxygenator exhaust capnography for prediction of arterial carbon dioxide tension during hypothermic cardiopulmonary bypass

Continuous monitoring and control of arterial carbon dioxide tension (P(a)CO2) during cardiopulmonary bypass (CPB) is essential. A reliable, accurate, and inexpensive system is not currently available. This study was undertaken to assess whether the continuous monitoring of oxygenator exhaust carbon dioxide tension (PexCO2) can be used to reflect P(a)CO2 during CPB. A total of 33 patients undergoing CPB for cardiac surgery were included in the study. During normothermia (37 degrees C) and stable hypothermia (31 degrees C), the values of PexCO2 from the oxygenator exhaust outlet were monitored and compared simultaneously with the P(a)CO2 values. Regression and agreement analysis were performed between PexCO2 and temperature corrected-P(a)CO2 and temperature uncorrected-P(a)CO2. At normothermia, a significant correlation was obtained between PexCO2 and P(a)CO2 (r = 0.79; p < 0.05); there was also a strong agreement between PexCO2 and P(a)CO2 with a gradient of 3.4 +/- 1.9 mmHg. During stable hypothermia, a significant correlation was obtained between PexCO2 and the temperature corrected-P(a)CO2 (r = 0.78; p < 0.05); also, there was a strong agreement between PexCO2 and temperature corrected-P(a)CO2 with a gradient of 2.8 +/- 2.0 mmHg. During stable hypothermia, a significant correlation was obtained between PexCO2 and the temperature uncorrected-P(a)CO2 (r = 0.61; p < 0.05); however, there was a poor agreement between PexCO2 and the temperature uncorrected-P(a)CO2 with a gradient of 13.2 +/- 3.8 mmHg. Oxygenator exhaust capnography could be used as a mean for continuously monitoring P(a)CO2 during normothermic phase of cardiopulmonary bypass as well as the temperature-corrected P(a)CO2 during the stable hypothermic phase of CPB.     

膀胱癌患者血清可溶性白细胞介素2受体的表达及其意义

对２４例膀胱移行细胞癌患者手术前后不同时期可溶性白细胞介素２受体（ＳＩＬ－２Ｒ）表达水平、白细胞介素２（ＩＬ－２）产生能力以及自然杀伤细胞毒因子（ＮＫＣＦ）活性进行了动态观察。结果表明，膀胱移行细胞癌患者ＳＩＬ－２Ｒ表达水平明显高于正常人，且ＳＩＬ－２Ｒ随肿瘤分期增高而逐渐升高；膀胱癌患者ＩＬ－２产生能力、ＮＫＣＦ活性明显低于正常人。术后膀胱移行细胞癌患者免疫功能呈现一个暂时抑制到逐渐恢复的过程。提示机体免疫功能变化与膀胱移行细胞癌的预后密切相关     

Mechanism of vascular smooth muscle cells activation by hydrogen peroxide: role of phospholipase C gamma.

BACKGROUND: Hydrogen peroxide (H2O2) formation is a critical factor in processes involving ischaemia/ reperfusion. However, the precise mechanism by which reactive oxygen species (ROS) induce vascular damage are insufficiently known. Specifically, activation of phospholipase C gamma (PLCgamma) is a probable candidate pathway involved in vascular smooth muscle cells (VSMC) activation by H2O2. METHODS: The activation of human venous VSMC was measured as cytosolic free calcium mobilization, shape change and protein phosphorylation, focusing on the role of tyrosine phosphorylation-activated PLCgamma. RESULTS: The exposure of VSMC to exogenous H2O2 caused a rapid increase in cytosolic free calcium concentration ([Ca2+]i), and induced a significant VSMC shape change. Both effects were dependent on a tyrosine kinase-mediated mechanism, as determined by the blockade of short-term treatment of VSMC with the protein tyrosine kinase inhibitor, genistein. Giving further support to the putative role of phospholipase C (PLC)-dependent pathways, the [Ca2+]i and VSMC shape change response were equally inhibited by the specific PLC blocker, 1-(6-((17-beta-methoxyestra-1,3,5(10)trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). In addition, U73122 had a protective effect against the deleterious action (24 h) of H2O2 on non-confluent VSMC. As a further clarification of the specific pathway involved, the exposure to H2O2 significantly stimulated the tyrosine phosphorylation of PLCgamma with a concentration- and time-profile similar to that of [Ca(2+)](i) mobilization. CONCLUSIONS: The present study reveals that H(2)O(2) activates PLCgamma on VSMC through tyrosine phosphorylation and that this activation has a major role in rapid [Ca(2+)](i) mobilization, shape-changing actions and damage by H(2)O(2) in this type of cells. These findings have direct implications for understanding the mechanisms of the vascular actions of H(2)O(2) and may help to design pharmacologically protective strategies.     

Pharmacokinetics of doxercalciferol, a new vitamin D analogue that lowers parathyroid hormone.

BACKGROUND: This is the first detailed pharmacokinetic report published on the administration of doxercalciferol [1alpha(OH)D(2)] recently introduced to treat secondary hyperparathyroidism. METHODS: 1alpha(OH)D(2) was administered in a range of single and multiple doses to volunteers with and without normal renal and/or hepatic function. Subsequent serial blood samples were assayed by HPLC/radioimmunoassay for the metabolite 1,25-dihydroxyvitamin D(2) [1,25(OH)(2)D(2)], the major active species. RESULTS: Bioavailability of 1,25(OH)(2)D(2) from a single 5 micro g 1alpha(OH)D(2) oral-capsule dose was estimated to be normally approximately 42% of that from a 5 micro g intravenous injection. Steady-state serum concentrations of 1,25(OH)(2)D(2) were attainable within 8 day, and fluctuated approximately 2.5-fold from peak to trough when oral 1alpha(OH)D(2) doses were taken every second day, and the terminal half-life was 34+/-14 h. Mean steady-state serum concentrations rose less than proportionally (from 20 to 45 pg/ml) on increasing oral 1alpha(OH)D(2) doses from 5 to 15 micro g every 48 h. Renal patients showed 39+/-37% increase in serum 1,25(OH)(2)D(2) concentration during 3-4 h haemodialysis sessions, but no other difference in steady-state pharmacokinetics was found between these or hepatically impaired patients and normal subjects. CONCLUSIONS: Given the sensitivity limits of current assays, the pharmacokinetics of this and other vitamin-D compounds is best elucidated from steady-state studies. The pharmacokinetics of 1,25(OH)(2)D(2) from 1alpha(OH)D(2) doses appears to be similar to that of 1,25(OH)(2)D(3) from 1alpha(OH)D(3) doses, albeit D(3) data have to date largely derived from single-dose studies. Deviation of 1,25(OH)(2)D(2) pharmacokinetics from linearity appears to be marginal enough to be clinically manageable with adequate precaution.     

Arachidonic acid for loading induced prostacyclin and prostaglandin E(2) release from osteoblasts and osteocytes is derived from the activities of different forms of phospholipase A(2)

Mechanical loading of bone stimulates resident bone cells to produce prostacyclin (PGI(2)) and prostaglandin (PG)E(2) by a mechanism that can be differentially regulated by ion channel blockers. We have investigated differences in the loading-related PG production mechanisms in rat ulnae explants loaded ex vivo. Loading and aluminium fluoride (AlF(3), a nonselective activator of G-proteins) both increased PGI(2) and PGE(2) release into culture medium. Pertussis toxin (PTX) blocked loading-related release of PGE(2), but not PGI(2), while isotetrandrine, an inhibitor of G-protein-mediated activation of phospholipase (PL)A(2), abolished the loading-related release of both PGs. This suggests both PTX-sensitive and -insensitive G-protein-dependent, PLA(2)-mediated mechanisms for loading-related PG production. Blockade of secretory (s)PLA(2) activity prevented loading-related release of PGE(2) and PGI(2), whereas inhibition of cytosolic (c)PLA(2) activity blocked loading-related release of PGE(2) alone. cPLA(2) was localized immuno-cytochemically to osteoblasts, but not to osteocytes. sPLA(2) was localized to osteocytes and osteoblasts. Exogenous type-IA sPLA(2) and type-IB sPLA(2) stimulated significant increases in PGE(2) and PGI(2) release. PTX reduced the release of both PGs stimulated by type IA PLA(2), but not type IB. Furthermore, inhibition of protein kinase C (PKC) activity blocked loading-related release of PGE(2), but not that of PGI(2). These data suggest that loading-related release of PGI(2) and PGE(2) utilizes arachidonic acid derived from the activity of different PLA(2)s. In osteocytes and osteoblasts, arachidonic acid for PGI(2) synthesis is liberated by PTX-insensitive G-protein-dependent sPLA(2) alone. In osteoblasts, arachidonic acid for PGE(2) synthesis is released by PTX-sensitive, G-protein-dependent, cPLA(2)-mediated activity, which also requires upstream sPLA(2) and PKC activities.