胖大海抑制草酸钙结晶形成的实验结果与临床观察

用胖大海提取液对草酸钙结晶形成的抑制进行了体外及动物实验研究，并观察尿石症患者与健康人２４小时尿液中尿石形成因素的差异及影响。结果：胖大海提取液含类葡萄糖氨基聚糖物质６９３．１ｍｇ／Ｌ；体外能抑制草酸钙结晶生长指数从４８．２％降至２５．８％；能抑制大白鼠肾内草酸钙结晶的生长和聚集，一水草酸钙含量从５．２６ｍｇ／ｇ减至１．５１ｍｇ／ｇ干肾组织（Ｐ＜０．００１）；尿石症患者和健康人尿量、ｐＨ、尿钙、草酸、尿酸及ＧＡＧｓ均无明显差异；尿石症患者尿ＧＡＧｓ含量从２９．２７ｍｇ／２４ｈ提高到３５．９４ｍｇ／２４ｈ（Ｐ＜０．０５）。胖大海在体内外对草酸钙结晶形成有明显抑制作用，在增加尿石症病人尿中ＧＡＧｓ排泄量，防治尿石症及其复发方面可能有应用价值。     

芭蕉芯和维生素B6对小鼠草酸钙结晶的抑制作用

观察了维生素Ｂ_６和芭蕉芯提取液对实验性高草酸尿症小鼠体内草酸钙结晶形成的抑制作用。结果发现：湿肾组织钙含量各组之间无显著性差异；湿肾组织草酸含量，维生素Ｂ_６治疗组为０．６９８０±０．４０８２μｍｏｌ／ｇ，芭蕉芯提取液治疗组为０．４０３１±０．２１４７μｍｏｌ／ｇ，均分别明显低于成石组（Ｐ＜０．０５及Ｐ＜０．０１）。偏光显微镜观察发现，服用维生素Ｂ_６及芭蕉芯提取液的小鼠肾脏草酸钙结晶形成明显少于成石组。结果表明：维生素Ｂ_６和芭蕉芯提取液都具有抑制实验性高草酸尿症小鼠肾脏草酸钙结晶形成的作用，其中，芭蕉芯提取液的抑制作用明显比维生素Ｂ_６强。     

钙敏感受体活性改变对大鼠泌尿系草酸钙结石形成的影响

目的探讨钙敏感受体（CaSR）活性改变对草酸钙结石形成的影响。方法在实验期间给予乙二醇和氯化铵诱导雄性SD大鼠产生泌尿系草酸钙结石。在造模期间给予不同剂量的CaSR抑制剂（NPS-2390）。实验结束时检测各组大鼠血尿素氮（BUN）、肌酐（Cr）、血磷、血钙、血镁、PTH的含量、24h尿量、尿pH值、尿钙、镁、尿草酸的分泌量,显微镜下观察肾组织切片中草酸钙结晶沉积及病理变化情况及肾脏中CaSR表达情况。从而评价CaSR活性的改变对泌尿系结石形成的影响。结果成石对照组大鼠血BUN、Cr、尿草酸、尿钙较空白组明显升高并且有大量结晶形成,表明建模成功。CaSR抑制剂组较成石对照组甲状旁腺激素（PTH）的分泌增加并且血Ca2＋升高尿钙升高。肾组织病理学检查显示CaSR抑制组的肾脏组织中的草酸钙结晶较成石对照组明显增加,组织病理损伤也较重。结论肾脏中及甲状旁腺中CaSR的表达下降可以导致草酸钙结晶的形成增加。     

经尿道绿激光汽化术联合肾镜下超声气压弹道碎石术治疗BPH并发膀胱结石（附26例报告）

目的：探讨腔内治疗BPH并发膀胱结石的有效方法。方法：采用经尿道前列腺绿激光汽化术（PVP）联合肾镜下超声气压弹道碎石术治疗BPH并发膀胱结石26例。结果：26例均一次手术成功，清石率达100％。无大出血、无膀胱穿孔及严重感染等并发症发生。术后住院3～5d，最大尿流率较术前明显改善。结论：绿激光汽化术联合肾镜下超声气压弹道碎石术治疗BPH并发膀胱结石，创伤小、恢复快、安全高效，是治疗BPH并发膀胱结石的理想方法。     

单味中药金钱草、石韦、车前子对肾结石模型大鼠的预防作用

目的：观察单味中药金钱草、石韦、车前子对肾结石的预防作用。方法：90只大鼠随机分为5组,采用1.25%乙二醇和1%氯化铵制备大鼠肾结石模型,用上述3种单味中药的免煎剂型分别给各实验组大鼠肾结石模型灌胃,对照组用枸橼酸钾,4周后观察尿和肾组织中草酸钙结晶的形成情况。结果：单味中药金钱草组、石韦组、车前子组大鼠肾内草酸钙结晶明显少于模型组,而与西药枸橼酸钾组相当。金钱草组、石韦组、车前子组大鼠尿中草酸钙结晶的排泄均明显多于模型组。结论：单味中药金钱草、石韦、车前子对预防大鼠肾结石的形成有确切效果,并与西药枸橼酸钾相当,其作用可能主要是通过增加尿中草酸钙结晶的排泄而达到的。     

苄丙酮香豆素对实验性大鼠肾草酸钙结石形成的影响

目的：探讨Vit．K拮抗剂苄丙酮香豆素(商品名华法令)对大鼠肾草酸钙结石形成的影响。方法：采用乙二醇饮水和氯化铵灌胃作成石剂，30只Wistar大鼠随机分为对照组(A组)、成石组(B组)、华法令组(C组)。饲养4周后，检测大鼠肾组织钙含量和草酸钙晶体形成、24h尿钙、尿草酸含量及血生化指标。结果：成石组和华法令组肾组织中钙、镁含量，24h尿草酸及尿钙、镁排泄量差异无显著性意义；镜下观察发现：华法令组大鼠肾脏草酸钙结晶形成多于成石组，但组间比较差异无显著性意义。结论：苄丙酮香豆素对大鼠肾草酸钙结石的形成无显著影响。     

前列腺增生症膀胱出口梗阻类型对剩余尿量的影响

目的：探讨前列腺增生症（BPH）所致膀胱出口梗阻（BOO）类型对膀胱排空及剩余尿量的影响。方法：根据直线被动尿道阻力关系（直线PURR）特点,从既往行尿动力学检查的BPH患者中选择68例,其中45例诊断为压迫型梗阻（压迫组）,23例为狭窄型梗阻（狭窄组）,所有患者逼尿肌收缩功能良好。对两组平均剩余尿量等尿动力学指标以及急性尿潴留发病率进行比较。结果：压迫组的剩余尿量显著高于狭窄组（P＜0．01）;压迫组15例（33．3％）、狭窄组1例（4．3％）有急性尿潴留病史,差异有极显著性意义（P＜0．01）;两组平均年龄、最大尿流率、最大逼尿肌压和梗阻程度的差异均无显著性意义。结论：BOO类型对膀胱排空障碍及剩余尿的产生有明显影响,压迫型梗阻患者易发生尿潴留。剩余尿量不能作为评价BPH患者逼尿肌功能和治疗预后的可靠指标。     

4种大鼠肾草酸钙结石模型的比较

目的筛选简便、快捷、成石效果好的SD大鼠肾草酸钙结石的造模方法。方法分别采用目前普遍使用的2种大鼠肾草酸钙结石的模型复制方法和2种改良的造模方法进行造模,并设立空白对照组,造模结束后采集每组大鼠24h尿量及血清,比较大鼠24h尿量、尿Ca2＋、尿Mg2＋、尿pH、尿草酸（0x）及血尿素氮（BUN）、肌酐（cr）、P、Ca2＋、Mg2＋,肾脏病理切片HE染色后光学显微镜下观察和比较各组大鼠肾脏病理改变及草酸钙结晶的沉积情况。结果E组[1％乙二醇＋2％氯化铵＋10％葡萄糖（48d）]在光学显微镜下草酸钙结晶沉积较传统组C组明显增多（P〈0．05）,但有30％大鼠死亡,血肌酐在5组大鼠中最高。D组[1％乙二醇＋2％氯化铵＋10％葡萄糖（28d）]较传统组C组草酸钙结晶沉积明显增多（P〈0．05）,并且造模时间短,大鼠存活率高（80％）,E组与D组相比结晶形成量无统计学意义（P〉0．05）,B组[1％乙二醇（28d）3肾脏中无肾结晶形成,仅有轻微的肾脏病理学改变,大鼠无死亡,肌酐不高。空白对照组无结晶形成,无病理改变。结论用1％乙二醇＋2％氯化铵＋10％葡萄糖诱导28天复制肾草酸钙结石模型的效果好,并且花费时间短,大鼠存活率高,建议选用。     

钬激光碎石术和经尿道等离子体电切加剜除术治疗BPH并膀胱结石的探讨

目的：探讨BPH并膀胱结石的有效治疗方法,为临床治疗BPH并膀胱结石的一期腔内治疗提供参考。方法：回顾性分析钬激光碎石术和经尿道等离子体电切加剜除术治疗BPH并膀胱结石患者36例的临床资料。结果：36例均一次手术成功,碎石时间15～45min,平均26min前列腺电切时间45～150min,平均65min。术中术后均无输血,无电切综合征、膀胱穿孔、结石残留等并发症。术后3～5天拔除尿管,无排尿困难、尿失禁等。病理检查结果均为BPH。术后3个月,国际前列腺症状评分（IPSS）由（22．6±4．8）分降至（7．8±1．5）分（P〈0．05）,最大尿流率（Qmax）由（6．3±2．5）ml／s升至（16．8±3．8）ml／s（P〈0．05）。结论：同期进行钬激光碎石术和经尿道等离子体电切加剜除术是一种治疗BPH并膀胱结石的高效、安全的方法。     

VitaK依赖蛋白及其羧化酶与草酸钙尿结石

尿中大分子蛋白物质尿凝血酶原与段1（UPTF1）因含γ－羧基谷氨酸（Gla）而与Ca∧2＋有高度亲和力，是一种强草酸钙结晶生长和聚集的抑制剂，与草酸钙尿石形成有密切关系。若其γ－羧基谷氨（Gla）羧化异常，与Ca∧2＋结合力降低，则有可能导致结石形成。     

Study on concretions developed around urinary catheters and mechanisms of renal calculi development

AIMS: To study the structure and composition of encrustation and concretions developed on urinary catheters to better understand their formation mechanism to be able to prevent them. METHODS: The surface of catheters was studied by direct and scanning electron microscopy observation. In vitro formation of encrustations was performed in synthetic urine. RESULTS: The surface of catheters was covered by a continuous layer of organic matter, on which a thin scale consisting of crystals of calcium oxalate monohydrate (COM), uric acid anhydrous or calcium phosphate developed. Encrustations observed on catheters generally exhibited the same composition as the previously developed renal calculi. In catheters collected from patients without previous episodes of renal calculi or with previous episodes of infected renal calculi in which infection was afterwards eradicated, on the first organic layer, in that case plate-like COM crystals forming a columnar layer were observed. In vitro experiments demonstrated that COM columnar structures were only formed when normocalciuric urine containing organic matter was used, and the presence of crystallization inhibitors, as phytate, notably delayed their formation. CONCLUSION: Calcium oxalate was the main crystalline phase developed on catheters inserted in patients, specially in the absence of urinary infection or urinary pH values <5.5 and high urinary uric acid levels. Thus, prophylaxis of encrustations may consist of preventive measures usually applied in cases of recurrent idiopathic calcium oxalate urolithiasis.     

Urine composition and stone formation during treatment with acetazolamide

Twelve patients who formed renal stones during acetazolamide treatment for glaucoma were studied. Calcium phosphate was the dominating component in the stones. Long term treatment with acetazolamide decreased urinary citrate markedly, which will result in an increased ion-activity product of calcium phosphate and a decreased inhibiting property of urine on calcium phosphate crystallization. The treatment also increased urinary oxalate which together with a low citrate might increase the risk of calcium oxalate crystallization. However, an estimate of the ion-activity product of calcium oxalate in urine (AP [CaOx]-index) was unaffected by the treatment and calcium oxalate was a minor component of the stones.     

Effect of vitamin C supplements on urinary oxalate and pH in calcium stone-forming patients

BACKGROUND: The contribution of ascorbate to urinary oxalate is controversial. The present study aimed to determine whether urinary oxalate and pH may be affected by vitamin C supplementation in calcium stone-forming patients. METHODS: Forty-seven adult calcium stone-forming patients received either 1 g (N=23) or 2 g (N=24) of vitamin C supplement for 3 days and 20 healthy subjects received 1 g. A 24-hour urine sample was obtained both before and after vitamin C for calcium, oxalate, magnesium, citrate, sodium, potassium, and creatinine determination. The Tiselius index was used as a calcium oxalate crystallization index. A spot fasting morning urine sample was also obtained to determine the urinary pH before and after vitamin C. RESULTS: Fasting urinary pH did not change after 1 g (5.8 +/- 0.6 vs. 5.8 +/- 0.7) or 2 g vitamin C (5.8 +/- 0.8 vs. 5.8 +/- 0.7). A significant increase in mean urinary oxalate was observed in calcium stone-forming patients receiving either 1 g (50 +/- 16 vs. 31 +/- 12 mg/24 hours) or 2 g (48 +/- 21 vs. 34 +/- 12 mg/24 hours) of vitamin C and in healthy subjects (25 +/- 12 vs. 39 +/- 13 mg/24 hours). A significant increase in mean Tiselius index was observed in calcium stone-forming patients after 1 g (1.43 +/- 0.70 vs. 0.92 +/- 0.65) or 2 g vitamin C (1.61 +/- 1.05 vs. 0.99 +/- 0.55) and in healthy subjects (1.50 +/- 0.69 vs. 0.91 +/- 0.46). Ancillary analyses of spot urine obtained after vitamin C were performed in 15 control subjects in vessels with or without ethylenediaminetetraacetic acid (EDTA) with no difference in urinary oxalate between them (28 +/- 23 vs. 26 +/- 21 mg/L), suggesting that the in vitro conversion of ascorbate to oxalate did not occur. CONCLUSION: These data suggest that vitamin C supplementation may increase urinary oxalate excretion and the risk of calcium oxalate crystallization in calcium stone-forming patients.     

Urinary crystallization inhibitors do not prevent crystal binding

PURPOSE: Renal stone formation requires the persistent retention of crystals in the kidney. Calcium oxalate monohydrate (COM) crystal binding to Madin Darby canine kidney strain I (MDCK-I), a cell line that resembles the epithelium in the renal distal tubule/collecting duct, is developmentally regulated, while LLC-PK1 cells (American Type Tissue Collection), which are widely used as a model of the renal proximal tubule, bind crystals irrespective of their stage of epithelial development. Whereas to our knowledge the binding molecules for COM at the surface of LLC-PK1 cells are still unknown, crystals adhere to the hyaluronan (HA) rich pericellular matrix transiently expressed by mobile MDCK-I cells. In the current study we investigated whether crystal binding to either cell type is influenced by urinary substances, including glycoprotein inhibitors of crystallization MATERIALS AND METHODS: We studied crystal binding to MDCK-I cells during wound repair, to confluent LLC-PK1 cells and to HA immobilized on a solid surface using [14C] COM pretreated or not pretreated with urine from healthy male volunteers. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis were performed to assess whether the crystals became coated with urine derived proteins RESULTS: Western blot analysis demonstrated that pretreated COM crystals were covered with protein inhibitors of crystallization. However, this protein coat had no significant effect on the level of crystal binding to either cell type. In contrast, the adherence of urine treated crystals to immobilized HA was significantly reduced CONCLUSIONS: The adherence of crystals to pericellular matrixes may encompass more than their simple fixation to the polysaccharide HA. Calcium oxalate crystal retention is not prevented by coating crystals with urinary constituents such as glycoproteins and, therefore, may predominantly depend on the surface properties of the renal tubular epithelium.     

Effects of urinary prothrombin fragment 1 in the formation of calcium oxalate calculus

PURPOSE: We investigated the effects of urinary prothrombin fragment 1 in the formation of calcium oxalate urolithiasis. MATERIALS AND METHODS: Fresh urine and renal parenchyma from patients with calcium oxalate calculus and normal controls were collected. Urinary prothrombin fragment 1 was isolated and purified from urine. It was identified by sodium dodecyl sulfide-polyacrylamide gel electrophoresis and analysis of its first 13 N-amino acids. The inhibitory activity of urinary prothrombin fragment 1 on calcium oxalate crystal growth was tested by the seeded crystallization technique. Meanwhile, the gamma-carboxyglutamic acid composition of urinary prothrombin fragment 1 was analyzed by a previously described method and genetic mutation of the gamma-carboxyglutamic acid domain of urinary prothrombin fragment 1 from renal parenchyma was detected by polymerase chain reaction-single strand conformational polymorphism sequencing. RESULTS: The gamma-carboxyglutamic acid composition of urinary prothrombin fragment 1 was significantly decreased from normal (24.4 to 1.7 mol/1,000 amino acids) in patients with calcium oxalate calculus. The mean growth index +/- SD of urinary prothrombin fragment 1 to calcium oxalate crystals was 42.3 +/- 4.2 compared with the normal index of 19.2 +/- 2.8 (p <0.01). The polymerase chain reaction-single strand conformational polymorphism sequencing technique revealed no genetic mutation of the gamma-carboxyglutamic acid domain of urinary prothrombin fragment 1 in patients with calcium oxalate calculus. CONCLUSIONS: The gamma-carboxyglutamic acid composition of urinary prothrombin fragment 1 as well as its ability to inhibit calcium oxalate crystal growth was significantly decreased in patients with calcium oxalate calculus. This was not caused by genetic mutation of the gamma-carboxyglutamic acid domain of urinary prothrombin fragment 1. It is important to elucidate the mechanisms of calcium oxalate stones in view of urinary prothrombin fragment 1.     

Effects of inositol hexaphosphate (phytate) on calcium binding, calcium oxalate crystallization and in vitro stone growth

PURPOSE: We measured and compared 3 activities of inositol hexaphosphate, also known as phytate, to explore their importance in relation to antilithogenic potential. MATERIALS AND METHODS: Calcium binding activity by inositol hexaphosphate was measured with a calcium electrode in artificial and whole urine. Calcium oxalate crystallization inhibition was measured by a 96-well plate turbidimetric method with artificial and whole urine. Effects on stone growth were measured in an in vitro system of 12 stones grown simultaneously (a stone farm) using artificial urine alone or supplemented with urinary macromolecules. RESULTS: Phytate decreased ionized calcium, increased the metastable limit, decreased the crystallization turbidity rate index and decreased the in vitro stone growth rate. The effective concentration for calcium binding reduction was about 2 orders of magnitude higher than that required for crystallization inhibition, which in turn was about 2 orders of magnitude higher than that required for stone growth inhibition. When human urine or artificial urine supplemented with urinary macromolecules was used, the effective concentration of phytate for inhibiting crystallization and stone growth was increased by about 1 order of magnitude. CONCLUSIONS: Inhibition of crystallization by phytate does not depend on decreasing the effective ionized calcium concentration and inhibition of in vitro stone growth does not depend on inhibiting crystallization of the suspended crystals. To our knowledge this is the first demonstration of a quantitative distinction between the inhibition of crystallization and stone growth. Inhibition of in vitro stone growth in the presence of macromolecules occurred at concentrations consistent with urinary phytate excretion.     

草酸钙结石患者尿中蛋白结合型γ-羧基谷氨酸的检测意义

目的　探讨含γ 羧基谷氨酸 (Gla)蛋白质及其Gla残基在尿石形成中的作用。　方法　采用过饱和结晶法从新鲜尿液中提取草酸钙晶体基质 ,高效液相色谱法 (HPLC)测定 2 5例草酸钙结石患者尿液和提取的晶体基质中蛋白结合型Gla含量。　结果　草酸钙结石患者尿蛋白结合型Gla浓度为 (1.32± 0 .2 4)nmol/ml,2 4h尿含量为 (2 .0 4± 0 .6 5 ) μmol,显著低于正常人 ;草酸钙结石患者尿液提取的晶体基质中蛋白结合型Gla含量亦显著低于正常人。　结论　草酸钙结石患者尿液中蛋白结合型Gla含量较少 ,尿液含Gla蛋白质的羧基化程度低下可能是结石形成的重要原因之一。     

前列腺增生症患者最小尿道开放压对剩余尿量的影响

目的　探讨前列腺增生症 (BPH )患者最小尿道开放压 (Pmuo)对剩余尿量的影响及其临床意义。方法　回顾性分析 12 7例BPH所致膀胱出口梗阻 (BOO)患者尿动力学检查和剩余尿量 (RUV)测定结果。根据Pmuo值将患者分为高Pmuo组和低Pmuo组 ,分别比较两组的RUV ,尿潴留发生率和有关尿动力学指标 ,并对RUV和Pmuo行相关分析。结果　①高Pmuo组的平均RUV显著高于低Pmuo组 (P <0 .0 5 ) ;②高Pmuo组有 2 3例 ( 2 6.4% )患者 ,低Pmuo组仅有 2例( 4 .4% )患者有急性尿潴留病史 ,差异有显著性 (P <0 .0 5 ) ;③高Pmuo组的平均PURR分级显著高于低Pmuo组 (P <0 .0 5 ) ;④相关分析显示Pmuo与RUV之间存在正相关 (r =0 .67,P <0 .0 5 )。结论　Pmuo对膀胱排空障碍及剩余尿的产生有明显影响。高Pmuo患者更易发生急性尿潴留。剩余尿量不能作为评价BPH患者逼尿肌功能和治疗预后的可靠指标     

Ascorbic acid in idiopathic recurrent calcium urolithiasis in humans – does it have an abettor role in oxalate, and calcium oxalate crystallization?

The role of ascorbic acid (ASC) in the pathophysiology of renal calcium stones is not clear. We evaluated ASC in blood and urine of fasting male patients with idiopathic calcium urolithiasis (ICU) and healthy volunteers. Using smaller subgroups, we also evaluated their response to exogenous ASC [either intravenous or oral ASC (5 mg/kg bodyweight)] administered together with an oxalate-free test meal. The influence of ASC on calcium oxalate crystallization, the morphology of crystals at urinary pH 5, 6 and 7, and the effect of increasing duration of urine incubation on urinary oxalate at these pHs, without and with addition of ASC, were studied too. In normo- and hypercalciuric ICU, blood and urinary ASC from fasting patients remained unchanged, but the slope of the regression line of urinary ASC versus urinary oxalate was steeper than in the controls; the plasma ASC half-life did not differ between controls, normo- and hypercalciuric ICU; the ASC-supplemented meal caused an increase in the integrated plasma oxalate in the normocalciuric subgroup versus controls. In normo- and hypercalciuric ICU urinary oxalate, the oxalate/glycolate ratio, and calcium oxalate supersaturation were increased, but urinary glycolate was unchanged. In the controls, oral ASC did not affect calcium oxalate crystallization, while in ICU, ASC inhibited crystal growth. In control urine calcium oxalate dihydrate and calcium oxalate monohydrate develops, while in ICU urine only the former crystal type develops. In vitro oxalate neoformation from ASC did not occur. It was concluded that (1) under normal conditions an abettor role of ASC for renal stones is not recognizable, (2) in ICU, urinary oxalate excess unrelated to degradation of exogenous ASC is exhibited, and that this is most likely unrelated to an initial increase in oxalate biosynthesis, and (3) ASC appears to modulate directly calcium oxalate crystallization in ICU, although the true mode of action is still not known. Received: 24 September 1999 / Accepted: 16 December 1999