Urinary bile acids during development of recurrent cholestasis of pregnancy

The pregnancies of two patients with mild intrahepatic cholestasis of pregnancy (RCP) were followed with detailed analyses of bile acids in urine. About twenty-five different bile acids were determined by GC/MS following separation according to mode of conjugation. The results were collated with the clinical course of the disease. The first detectable change in bile acid excretion was the appearance of tetrahydroxylated bile acids at about the 30th gestational week. Somewhat later and concomitant with the rise in urinary oestriol, the total bile acid excretion started to increase. In one of the patients, who had a maximum total excretion of 84 mumol/24 h, deoxycholic acid was a major constituent, comprising about 40% of the total. The same patient had only slightly elevated levels of tetrahydroxylated bile acids and serum amino-transferases. The possible effect of low-fat diet on these results is discussed. Monohydroxylated bile acids were present throughout the pregnancies in small amounts and their role as aetiological factors is discussed. The care of RCP patients is outlined, and the need for simple, specific and quantitative methods for following the course of RCP is pointed out.     

血清总胆汁酸在正常妊娠过程中的变化

目的　探讨孕妇血清总胆汁酸 (TBA)在正常妊娠过程中的变化。方法　用酶法检测孕妇血清中的TBA水平。结果　早孕、中孕和晚孕组的孕妇血清中TBA水平分别较非妊娠组升高 8.2 %、33.8%和 6 7.8% ,而且晚孕组比中孕组的孕妇血清中TBA水平也有明显升高。结论　血清TBA在妊娠过程中持续升高 ,孕妇在妊娠时就有潜在发生妊娠性肝内胆汁瘀积症 (ICP)的危险。     

血清总胆汁酸测定在妊娠肝内胆汁淤积症诊断中的意义

目的 测定健康孕妇和妊娠肝内胆汁淤积症(ICP)患者血清总胆汁酸(TBA)水平,与其他肝功能指标比较,探讨TBA水平对ICP诊断的意义.方法 采用循环酶法,在Olympus AU2700全自动生化仪上,对20例ICP患者、30例健康孕妇进行TBA、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)检测.结果 ICP患者组血清TBA水平(35.1土7.O)μmol/L,明显高于健康孕妇组(2.9士1.6)μmol/L,差异有统计学意义(t=20.544,P＜0.01).ICP患者组TBA异常率为90.O%,高于ALT、AST、ALP异常率(55%、50%、60%),ICP组TBA水平均值较健康孕妇组升高12.1倍,明显高于ALT、AST、ALP的升高倍数(4.3、3.4、3.6).结论 血清TBA测定对ICP的诊断有较大意义,其敏感性和特异性优于其他肝功能项目.     

血清肝胆酸及总胆汁酸联合检测在妊娠期肝内胆汁淤积症中的临床意义

目的探讨血清肝胆酸(CG)及总胆汁酸(TBA)联合检测在妊娠期肝内胆汁淤积症(ICP)中的临床意义。方法选择85例妊娠期胆汁淤积症患者(ICP组)及85例健康妊娠孕妇(健康对照组),分别检测2组研究对象的CG、TBA、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBIL),并对结果进行比较。结果 ICP组血清血清CG和TBA水平明显高于健康对照组,差异有统计学意义(P0.05);ALT、AST、TBIL与健康对照组比较,差异也有统计学意义(P0.05);ICP组血清CG和TBA联合检测阳性率高于健康对照组,差异有统计学意义(P0.05)。结论妊娠期ICP时,血清CG、TBA明显升高,可作为ICP诊断的敏感指标,两者联合检测对ICP的早期诊断及监测具有重要的临床意义。     

Tetrahydroxylated bile acids in healthy human newborns

Urine was collected in four healthy infants, born after 35-39 weeks of gestation. The collections were made for 24 h starting immediately after birth. Bile acids were extracted, separated into conjugate groups, solvolysed, hydrolysed and quantified by gas-liquid chromatography as methyl ester trimethylsilyl ether derivatives. Identification was made by gas-liquid chromatography-mass spectrometry. Cholic acid was the predominating primary bile acid. Non-sulphated tetrahydroxylated bile acids, tentatively identified as 1,3,7,12- and 3,6,7,12-tetrahydroxycholanoic acids, were present in almost the same amounts as cholic acid. A previously unknown tetrahydroxylated cholanoic acid, which might be 2-hydroxylated hyocholic acid, was found in all infants in similar amounts. 3 beta-Hydroxy-5-cholenoic acid was present in the sulphate fraction in the urine from all infants. Lithocholic acid was not found. Small amounts of allo and 6-hydroxylated bile acids were mainly found in the sulphate fraction. Bile acids hydroxylated in the 1-position were found predominantly in the taurine fraction.     

护理干预在妊娠期胆汁淤积综合征患者中的应用

目的:探讨综合护理干预在妊娠期胆汁淤积综合征患者中的的临床应用价值.方法:选择2009年1月-2011年1月在我院进行分娩的82例妊娠期肝内胆汁淤积综合征患者,将35例在我院门诊筛查并入院确诊为妊娠期肝内胆汁淤积综合征,接受治疗,然后在我院分娩的患者作为治疗组,47例因未在我院进行产前检查,入院时诊断为妊娠期肝内胆汁淤积综合征但已临产或近临产未能接受治疗的为对照组,对照组采取常规护理,治疗组采用护理干预.比较两组患者的临床护理效果.结果:对照组新生儿窒息、羊水粪染、剖宫产比例明显高于治疗组(P＜0.05);而两组早产、新生儿死亡、产后出血率比较差异无明显的统计学意义(P＞0.05);治疗组ALT、AST、CG指标明显低于对照组(P＜0.05).结论:综合护理干预可以减少妊娠期胆汁淤积综合征患者的不良预后,值得临床推广应用.     

应用高效液相色谱法建立妊娠肝内胆汁淤积症的胆汁酸谱

目的 用反相高效液相色谱（RP—HPLC）测定妊娠肝内胆汁淤积症（ICP）患者血清9种甘氨结合胆汁酸和游离胆汁酸的浓度，建立ICP疾病的胆汁酸谱，以增加对ICP诊断的灵敏度和特异性。方法 用柱前衍生RP—HPLC法测定11例ICP患者，11例乙肝患者，11名正常孕妇血清9种胆汁酸浓度。结果 ICP患者血清胆汁酸以甘氨胆酸（GCA）和甘氨鹅脱氧胆酸（GCDCA）增高为主，约为正常孕妇的20倍，GCA：GCDCA约为3．5：1；ICP患者血清游离胆汁酸的浓度与正常孕妇相似；ICP与乙型肝炎伴转氨酶轻中度增高的胆汁酸谱也不同。因而ICP患者的胆汁酸谱具有一定的特异性，可以对ICP进行诊断及与乙肝进行鉴别诊断。结论 本研究在国内首次报道了ICP患者的特征胆汁酸谱，将有助于ICP的诊断和鉴别诊断。     

妊娠期肝内胆汗淤积症对胎儿影响的初步研究

目的探讨妊娠期肝内胆汁淤积症（ICP）对胎儿的影响。方法选择孕足月ICP产妇40例为观察组（ICP组）,正常孕足月产妇40例为对照组,分娩后测定脐静脉血清胆汁酸（TBA）、丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、肿瘤坏死因子-α（TNF-α）。结果 ICP组脐静脉血清胆汁酸（TBA）、ALT、AST、TNF-α均明显高于正常组,差异有统计学意义（P〈0.05）。结论 ICP能造成胎儿肝功能异常,能导致胎儿有害细胞因子增加。     

妊娠期肝内胆汁淤积症的危险因素分析

目的 探讨妊娠期肝内胆汁淤积症(ICP)的危险因素,为改善孕妇及围产儿结局提供科学参考.方法 回顾性选取2018年1～6月重庆市南川区人民医院收治的90例ICP患者作为病例组,并随机选择同期分娩的90例非ICP孕产妇作为对照组.收集孕妇年龄、身高、体重、乙肝病毒感染、肝胆疾病、甲状腺疾病、血液系统疾病、妊娠期高血压以及...     

Enzymic measurement of primary bile acids and the primary bile acid ratio in serum with the IL-Multistat III Fluorescence Light-Scattering Centrifugal Analyzer

Enzymic fluorimetric methods are described for the determination of primary bile acids and of chenodeoxycholic acid (CDC) and cholic acid (C) in serum. Bile acids are extracted from 0.3 mL of serum in a simple 5-min step with use of Sep-Pak C cartridges. Total primary bile acids are measured by an equilibrium technique after reaction with beta-NAD in the presence of 7 alpha-hydroxysteroid dehydrogenase. Chenodeoxycholic acid (and its conjugates) is measured by a reaction-rate technique employing the same reaction as above but under different experimental conditions. A small contribution of cholic acid (and its conjugates) to the reaction rate is eliminated by simple calculations. Cholic acid is calculated by difference of the two determinations. In both assays NADH fluorescence is measured with the Multistat centrifugal analyzer. Absolute recovery of bile acids from serum was about 87%. Day-to-day standard deviations for CDC and C were 1.6 and 2.0 mumol/L at serum concentrations of 22.1 and 24.1 mumol/L respectively. Comparison data with a cholylglycine RIA procedure gave the following correlation coefficients (x = RIA, y = proposed method): r = 0.980 (RIA vs total primary bile acids), r = 0.918 (RIA vs CDC) and r = 0.989 (RIA vs C). The methods described appear more practical for use on a routine basis than methods in the literature for the calculation of the primary bile acid ratio.     

Effects of bile and bile acids on cultured human fibroblasts

Impaired healing induced by leakage of bile has been postulated as one factor responsible for complications after reconstructive bile duct surgery. The cytotoxicity of human bile and its major bile acids on cultured human fibroblasts was therefore studied by evaluation of their effects on cell morphology and growth, on synthesis and secretion of 35SO4-mucopolysaccharides and on release of a lysosomal enzyme. Normal human fibroblasts derived from a standard culture strain (MRC-5) were grown to confluence and exposed to: (1) sterile human T-tube bile, (2) a mixture of bile acids resembling that of human bile, or (3) various concentrations of the glycine- and taurine conjugates of cholic, chenodeoxycholic or deoxycholic acid. Medium containing whole bile (total bile acid concentration 0.25, 0.75 or 1.6 mmol/l) exerted time and dose dependent cytotoxic effects on morphology and growth and release of lysosomal enzyme. Synthesis and secretion of 35SO4-mucopolysaccharides were markedly inhibited. The bile acid mixture exhibited the same time and dose dependent effects. The conjugates of deoxycholic acid were found to be the most toxic of the individual bile acids studied.     

Biliary bile acids in uncomplicated pregnancy and in cholestasis of pregnancy

Conjugated and sulfated bile acids were determined by gas-liquid chromatography and by high-pressure liquid chromatography in gallbladder bile samples of four pregnant women at term and of two patients with cholestasis of pregnancy. In healthy pregnant women the mean ratio of cholyl/chenodeoxycholyl/deoxycholyl glycine was 3.7 : 1 : 0.23 and that of taurine conjugates 3.0 : 1 : 0.25, respectively. In gallbladder bile pool of non-pregnant females these ratios were 1.0 : 1 : 0.00 and 1.0 1 : 0.70, respectively. Thus cholic acid predominated in pregnancy bile. In patients with cholestasis of pregnancy, cholid acid comprised 90% of total biliary bile acids, the proportion of chenodeoxycholic acid was greatly decreased and nonsulfated deoxycholic acid was not detected. The proportion of sulfated bile acids of total biliary bile acids was between 0.4 and 1.2% in uncomplicated pregnancy and 0.3 and 0.5% in cholestasis patients.     

Inhibition of ileal bile acid transport by cyclosporin A in rat

Abstract. Chronic administration of cyclosporin A may induce cholestasis and this effect has been attributed to impaired hepatic bile salt synthesis, metabolism and transport. We investigated the effect of cyclosporin A on intestinal absorption of bile acids in the ileum of rat. Ileal bile acid absorption was measured by in vivo intestinal perfusion with cyclosporin A and the solvent Cremophor EL. During ileal perfusion with 25 μM glycocholic acid, the concentration of 2.8 mm cyclosporin A inhibited intestinal bile acid absorption on average by 34%. Additional experiments were performed with everted gut sacs of the distal ileum to evaluate active absorption. A dose and time dependent inhibition of the active intestinal absorption of bile acids was found, with a 50% transport inhibition at an average cyclosporin A concentration of 2.69mmolL^-'. Thus, cyclosporin A inhibits the active intestinal absorption of bile acids which may influence bile acid synthesis, turnover and secretion and may contribute to cyclosporin A induced cholestasis.     

Bile acids and their sulphated and glucuronidated derivatives in bile, plasma, and urine of children with intrahepatic cholestasis: effects of phenobarbital treatment

Abstract. Bile acids and their sulphated and glucuronidated derivatives were studied in three children with persistent intrahepatic cholestasis, two children with intrahepatic biliary hypoplasia, and four healthy children. In children with cholestasis, biliary bile acids consisted of 11(±0–3) % 3 β-hydroxy-delta-5-cholenoic acid, 2-1(± 0–6) % lithocholic acid, 2-2(± 11) % deoxy-cholic acid, 5–8(±2-2) % ursodeoxycholic acid, 39-1(± 1 -4) % chenodeoxycholic acid, 0–5(± 0 2) % hyo-cholic acid, and 49-3(± 3 0) % cholic acid. Of these bile acids 121 (±l 9) % were sulphated and 4–5 (±0 6) % were glucuronidated. In healthy children, biliary bile acids consisted of 0–7 (±0–4) % lithocholic acid, 3–4 (±0 8.) % deoxycholic acid, 0–1 (±0 1) % ursodeoxycholic acid, 32-7 (±6 9) % chenodeoxycholic acid, and 631 (±7 1) % cholic acid. Of these bile acids, 0–6±0 1 % were sulphated and 0–2 ±0 1% were glucuronidated (mean ± SEM). In the urine of healthy children, 3-3(±0 6) mg/24 h bile acids (1–5±0 3 mg sulphates and 0–1 ±0 1 mg glucuronides) were excreted, in the urine of children with cholestasis 61-4 (± 10 2) mg/24 h (30 2 ±7 1 mg sulphates and 5 6 ±1 2 mg glucuronides) were excreted. Thus in children with cholestasis the amounts of sulphated and glucuronidated bile acids are greater than in healthy controls. Substantial amounts of sulphated and glucuronidated bile acids are excreted in bile and urine of these patients. Phenobarbitone treatment in the five children with cholestasis led to a reduction of serum bile acids from 90 4 (± 13 2) μg/ml to 39 3(±3 6) μ//ml, a relative increase of bile acid glucuronides in bile from 45 (±0 6)% to 8 l(±0 6)%, a slight alteration of the bile acid sulphates in bile from 121(±l 9) % to 111 (± 1 2)% and no alteration of the bile acid spectrum. Urinary excretion of bile acids decreased from 61 4 (± 10 2) mg/24 h to 34 7(±3 0) mg/24 h. Phenobarbitone treatment of children with cholestasis thus induced glucuronidation of bile acids but had no significant effect on sulphation or on formation of individual bile acids.     

妊娠期肝内胆汁淤积症67例临床分析

目的 探讨妊娠期肝内胆汁淤积症(ICP)的危害、监护与诊治方法.方法 以67例ICP患者为研究对象,并选择同期分娩的70例非ICP患者作为对照组,进行回顾性分析.结果 研究组胎儿窘迫率、羊水污染率、早产率、剖宫产率及产后出血率均显著高于对照组,差异有显著性(P＜0.05).结论 ICP对胎儿危害严重,及时诊断、积极治疗、密切胎儿监护并适时终止妊娠能有效改善妊娠结局.     

Immunosuppressive effects of endotoxins and bile acids in vivo in the rat

Cell-mediated immunity is impaired during cholestasis. The aim of this study was to evaluate in vivo the effects on this immune defect of high serum levels of endotoxin and bile acids. Heterotopic cardiac allotransplantations were performed in the DA/Lewis rat combination. Cholestasis, induced by ligation/section of the common bile duct, was responsible for a significant delay in the rejection time (16 ± 0.5 vs. 7.1 ± 0.4 days in controls, P <0.01). Elimination of Gram-negative intestinal bacteria from cholestatic rats by a vancocin/colimycin/tobramycin (VCT) mixture induced a significant reduction in endotoxin levels and a reduction in rejection times (9.5 ± 1.0 days, P <0.01) that remained, however, significantly longer than those of controls ( P <0.05). Oral administration of chenodeoxycholic acid in non-cholestatic rats significantly enhanced the serum concentration of total bile acids (60.6 ± 15.3 μmol L⁻¹ vs. 17.4 ± 1.9 μmol L⁻¹ in controls, P <0.01) and postponed allograft rejection (10.7 ± 0.6 days, P <0.01 vs. controls). These data suggest that increased endotoxin level and serum bile acid concentration may play a role in the immunosuppressive effect of cholestasis.     

气相色谱-质谱联用法检测粪便中短链脂肪酸

摘要：目的：建立气相色谱-质谱联用快速检测粪便中短链脂肪酸的方法,并探讨将其应用于肠道疾病辅助诊断的可能性。 方法：分别取健康C57BL/6小鼠、SD大鼠和成年人志愿者粪便,以及用硫酸葡聚糖溶液诱导的肠炎模型C57BL/6小鼠的粪便;用气相色谱-质谱联用法检测上述标本中短链脂肪酸的种类和相对丰度。 结果：所有标本均检测出多种短链脂肪酸,其种类主要有乙酸、丙酸、丁酸和戊酸。在生理条件下,人与鼠短链脂肪酸的种类和相对丰度比都十分相似。肠炎可使粪便中除乙酸外的其他短链脂肪酸的相对丰度下降,其中,尤以丁酸下降最为明显。 结论：气相色谱-质谱联用法可快速检测粪便中的短链脂肪酸,并有可能应用于肠炎等肠道疾病的辅助诊断。     

不同临床分度妊娠期肝内胆汁淤积症对围产儿结局及分娩方式的影响

目的探讨不同临床分度妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy,ICP）处理时机与方式,以降低围产儿病率及死亡率。方法根据发病孕周及孕妇血清胆汁酸、丙氨酸转氨酶、门冬氨酸转氨酶、血清总胆红素、直接胆红素水平,将ICP分为轻度与重度,分别予以不同处理,比较其终止妊娠时机和方式与围产儿结局。结果轻度ICP 291例,重度ICP 183例,终止妊娠孕周分别为（38.3±1.5）周和（35.2±1.1）周,两组比较差异有统计学意义（P〈0.01）;重度组胎儿宫内窘迫、新生儿窒息、早产发生率均明显高于轻度组,差异有统计学意义（P〈0.01）。结论产前对ICP进行临床分度及处理,有助于选择终止妊娠时机和分娩方式,从而降低围产儿病率及死亡率。     

Accurate enzymatic measurement of fecal bile acids in patients with malabsorption

Quantitation of fecal bile acid excretion can help elucidate the cause of diarrhea or steatorrhea. Fecal bile acids can be measured with gas chromatography-mass spectrometry, but this is time-consuming, expensive, and not available for clinical use. Relatively simple enzymatic methods have been described for the measurement of fecal 3alpha-hydroxy bile acids, but these have not been validated in patients with gastrointestinal disease. We found that an enzymatic method yielded falsely low results in patients with malabsorption syndromes for two reasons: First, the preliminary hydrolysis step did not completely deconjugate bile acids, precluding their extraction into diethyl ether for enzymatic assay. Second, long-chain fatty acids inhibited 3alpha-hydroxysteroid dehydrogenase activity. By increasing the duration of hydrolysis and the concentration of enzyme, we developed a simple, accurate, and reproducible method for measuring fecal 3alpha-hydroxy bile acids that agreed well with values obtained with the use of gas chromatography-mass spectrometry (R =.95), both in normal subjects and in patients with malabsorption syndromes.     

妊娠期肝内胆汁淤积症患者血清胆汁酸及血液流变学指标变化及其临床意义

目的 探讨妊娠期肝内胆汁淤积症（ICP）患者血清胆汁酸（TBA）和血液流变学指标变化及其临床意义.方法 选择单胎妊娠ICP患者30例为ICP组、单胎正常妊娠妇女18例为正常妊娠组,并根据胎儿是否出现胎内窘迫将ICP组分为ICP缺氧组（14例）和ICP正常组（16例）.测试每组母血及胎儿脐带血的TBA值及脐带血血液流变学指标,包括全血还原黏度（RV）、血浆黏度（PV）、全血比黏度高切（HS）、全血比黏度低切（LS）、红细胞压积（HCT）变化.结果 ICP缺氧组的TBA水平明显高于ICP正常组及正常妊娠组（P＜0.05或P＜0.01）;ICP正常组与正常妊娠组的TBA水平差异亦显著（P＜0.01）;ICP缺氧组各血液流变学指标值均明显高于正常妊娠组（P＜0.05或P＜0.01）,且RV、LS及HCT显著高于ICP正常组（P＜0.05或P＜0.01）.ICP正常组与正常妊娠组的RV、PV、LS、HCT有明显统计学差异（P＜0.01）.结论 ICP患者TBA水平升高及血流变学的指标变化可以作为临床预测胎儿窘迫的重要指标.