肝功能衰竭肝性脑病大鼠5-羟色胺和去甲肾上腺素的变化

目的研究5-羟色胺(5-HT)及去甲肾上腺素(NA)在大鼠急性肝功能衰竭(ALF)和慢性肝功能衰竭(CLF)肝性脑病时的变化。方法将110只SD大鼠随机分为正常对照组(20只)、ALF组(45只)及CLF组(45只)。ALF模型按500mg/kg硫代乙酰胺(TAA)间隔24h两次灌胃;CLF模型按质量分数为0.03%的TAA作为饮用水灌饲10周,并根据每周体重的变化增减50%的TAA含量。造模成功后从眼底静脉丛取血,检测5-HT、NA、血氨和肝功能指标;处死动物,取肝、脑组织,光镜下观察组织病理学变化。结果ALF组和CLF组均出现不同程度的肝功能损害表现,血中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL)、白蛋白(ALB)、白蛋白/球蛋白(A/G)、血氨均有明显变化(P<0.05或P<0.01);肝脏及脑组织病理学符合ALF和CLF肝性脑病表现。ALF组和CLF组5-HT(16.06±1.08)μmol/L和(15.32±1.48)μmol/L均较正常对照组(2.75±0.26)μmol/L显著升高(P均<0.01),CLF组NA值下降(94.0±2.13)pmol/L比(121.2±14.8)pmol/L,P<0.05。结论5-HT在大鼠ALF和CLF所致肝性脑病时明显升高;NA在大鼠CLF所致肝性脑病时明显下降。     

幽门螺旋杆菌感染与肝硬化高氨血症及肝性脑病发病的相关性研究

目的 了解幽门螺旋杆菌(HP)感染与血氨水平及肝性脑病(HE)发病的相关性,探讨根除HP对血氨水平和HE发病的影响.方法 收集368例肝硬化患者,记录其性别、年龄、数字连接试验(NCT)结果、HP感染率、肝功能Child-Pugh分级、血氨水平和HE情况.HP阳性患者予以奥美拉唑+克拉霉素+阿莫西林1周根除治疗,1个月后复查13C尿素呼气试验,记录患者的神经、精神症状和血氨水平.结果 ①本组肝硬化患者的HP感染率为70.1%(258/368例);HE发生率为51.4%(189/368例);未发生HE的肝硬化患者中,179例进行了NCT,检出亚临床肝性脑病(SHE)患者85例(占47.5%).②HP阳性肝硬化患者血氨浓度[(79.3±61.8)μmol/L]显著高于HP阴性者[(52.7±49.8)μmol/L,P＜0.01];根除HP后血氨水平明显下降[(52.6±36.5)μmol/L,P＜0.01].HP阳性和HP阴性肝硬化患者HE发生率比较差异有显著性(59.6%比31.8%,P＜0.01);根除HP后HE发生率降至32.8%,与根除前比较差异有显著性(P＜0.01).③HE、SHE和肝硬化患者的HP感染率分别为81.5%、68.5%和53.9%(P均＜0.05),HE患者的血氨水平[(96.6±78.2)μmol/L]显著高于SHE患者[(60.5±50.4)μmol/L]和肝硬化患者[(46.8±36.4)μmol/L,P均＜0.01].结论 HP感染可加重肝硬化高氨血症,促成HE发作,根除HP有助于治疗和预防肝硬化HE发生.     

SARS患者的肝脏损害

目的　研究严重急性呼吸综合征 (SARS)患者肝脏功能和肝组织病理学的变化 ,探讨 SARS患者肝脏损害的可能机制及其临床意义。方法　依据中华人民共和国卫生部诊断标准 ,选择 2 0 0 3年 2— 6月收治的 SARS患者 110例检测肝脏功能 ,其中 8例死亡者行肝组织病理学检查 ;并与健康体检者 35例进行比较。结果　 SARS组患者血清丙氨酸转氨酶 (AL T)、天冬氨酸转氨酶 (AST)、总胆红素 (TBil)、乳酸脱氢酶(L DH)水平均显著高于对照组 ,分别为 (91.6 1± 5 0 .5 3) U/ L 比 (32 .91± 10 .5 6 ) U/ L,(78.6 8± 33.32 ) U/ L 比(2 9.4 3± 8.89) U/ L,(11.6 7± 4 .2 6 ) μmol/ L 比 (8.4 4± 3.86 ) μmol/ L,(42 9.95± 188.94 ) U/ L 比 (2 0 0 .83±4 4 .86 ) U / L ,P均 <0 .0 0 1;白蛋白 (AL B)和前白蛋白 (PAB)均明显低于对照组 ,分别为 (34.4 0± 5 .13) g/ L比(42 .0 9± 6 .79) g/ L和 (0 .2 0± 0 .0 6 ) g/ L比 (0 .34± 0 .0 5 ) g/ L ,P均 <0 .0 0 1;血清直接胆红素 (DBil)、总胆汁酸 (TBA)、γ谷氨酰转肽酶 (GGT )、碱性磷酸酶 (AL P)水平与对照组无差异 (P均 >0 .0 5 )。 AL T、AST、GGT、L DH变化范围较大 ,为正常范围 4～ 9倍 ,其余各项变化范围较小。AL T、AST和 PAB异常率达 80 .0 %以上 ,AL     

肝移植术前测定氧自由基相关指标在预后判别中的价值

目的 :研究肝移植患者术前体内氧自由基的相关指标及与预后的关系。方法 :测定了 18例肝移植患者术前血浆中脂质过氧化物 (LPO)、总抗氧化能力 (TAC)、一氧化氮 (NO)、总胆红素 (T BIL ) ,分析其与预后的关系。结果 :死亡组血浆 L PO(17.13± 4.16)μmol/ L ,明显高于存活组 (7.97± 3 .5 2 )μmol/ L (P<0 .0 5 ) ,存活组血浆 TAC(3 8.0 5± 19.13 ) k U / L ,高于死亡组 (3 2 .5 4± 3 .0 7) k U/ L,但无显著性差异 (P>0 .0 5 ) ;存活组血浆NO (5 0 .46± 19.5 4)μmol/ L,死亡组 (5 0 .80± 14 .80 )μmol/ L ,无显著性差异 (P>0 .0 5 ) ;死亡组血 T BIL(4 2 5 .98± 2 14 .18) μmol/ L,明显高于存活组 (172 .10± 14 4.3 2 ) μmol/ L(P<0 .0 5 )。从结果筛选出对判断预后有意义的指标为血浆 LPO和血浆 TAC,建立根据术前检验指标预测术后死亡与存活的判别函数式分别为 :Y1 =0 .3 2 90 X1 + 0 .0 998X2 ,3 .90 40 ,Y2 =1.3 5 2 0 X2 -0 .0 5 0 0 X2 -11.464 0 (其中 X1 为血浆 LPO,X2 为血浆 TAC) ;判别方程对存活组判别正确率为 10 0 .0 % ,对死亡组判别正确率为 83 .3 % ,总的判别正确率为94.4%。结论 :术前检测血浆 LPO和 TAC能较正确判断患者的死亡危险程度 ,可作为术前常规检查。判别方程判别     

Reduced acetylcholinesterase activity in erythrocyte membranes from patients with phenylketonuria

OBJECTIVE: a) To evaluate acetylcholinesterase (AChE) activities in erythrocyte membranes from phenylketonuric (PKU) patients and controls and to correlate with their plasma phenylalanine (Phe), tyrosine (Tyr), alanine (Ala) and dopamine (DA) levels. b) To determine the in vitro effects of Phe, Ala and Phe plus Ala on their AChE activities. DESIGN AND METHODS: AChE activities were determined spectrophotometrically in erythrocyte membranes from PKU children (n = 12) adhering to their diet (group A), from 11 "off diet" (group B) and from 23 controls. Their plasma amino acids were evaluated with an amino acid analyser and DA with an HPLC method. Ala (1.8 mM) and/or Phe (1.8 mM) were added in the enzyme incubation medium from controls, whereas only Ala was added in that from group B. RESULTS: AChE activity (1.19 +/- 0.05 deltaOD/min x mg protein), Tyr (46 +/- 17 micromol/L) and DA (56 +/- 18 micromol/L) were remarkably decreased by about 60% in group B as compared to those of group A (3.01 +/- 0.18 deltaOD/min x mg protein, 115 +/- 39 micromol/L, 137 +/- 29 micromol/L, respectively, p < 0.001) and controls (3.13 +/- 0.16 deltaOD/min x mg protein, 117 +/- 44 micromol/L, 142 +/- 22 micromol/L, respectively, p < 0.001). Phe negatively correlated with AChE activity and positively with plasma Tyr and DA. Ala reversed the inhibited AChE by Phe in erythrocyte membranes from healthy children to control values, whereas no reverse effect was observed on the enzyme activity from PKU patients. CONCLUSIONS: a) The low levels of DA and its precursor Tyr are due to the high Phe blood levels, as a consequence of the decreased activity of Phe-hydroxylase in the liver of our patients. So, high Phe blood levels inhibit AChE in PKU patients, probably resulting in higher acetylcholine concentrations. b) Determination of AChE in erythrocyte membranes from PKU could be a useful marker for the neurotoxic effects of Phe.     

Plasma homocysteine levels in patients with beta-thalassaemia major

OBJECTIVE: We investigated the level of homocysteine (HCY) and its relation with vitamin B12, folate and oxidative stress in patients with beta-thalassaemia major. MATERIAL AND METHODS: Plasma HCY, methionine, advanced oxidation protein products (AOPP) and serum vitamin B12, folate, ferritin and total antioxidant capacity (TAC) were determined in 32 thalassaemic patients and 27 control subjects. RESULTS: HCY (6.44+/-0.44 versus 8.71+/-0.57 micromol/L), methionine (12.57+/-1.8 versus 22.2+/-3.8 micromol/L), folate (9.14+/-0.48 versus 15.38+/-0.71 nmol/L) and TAC (0.34+/-0.03 versus 0.56+/-0.03 mmol/L) significantly decreased in thalassaemic patients, whereas AOPP (20.26+/-1.8 versus 11.30+/-0.2 micromol/L) and ferritin (3481.0+/-512 versus 46.9+/-4.6 ng/mL) significantly increased. Vitamin B12 levels were similar in both groups (259.1+/-16.6 versus 228.9+/-7.4 pmol/L). CONCLUSIONS: These findings suggest that increased and uncompensated oxidative stress may lead to an increment in HCY catabolism in thalassaemic patients.     

Caspase-cleaved cytokeratin 18 and 20 S proteasome in liver degeneration

Apoptosis of epithelial hepatocytes plays a pivotal role in acute as well as in chronic liver diseases. The cleavage of cytokeratin-18 (CK-18) by caspases is an early event in the apoptotic process. We therefore sought to investigate serum levels of CK-18 and 20S proteasome in patients with liver cirrhosis, primary graft dysfunction (PDF), and acute liver failure (ALF), and in healthy volunteers. Enzyme-linked immunosorbent assay (ELISA) was utilized to measure the concentration of M30, a fragment of CK-18 cleaved at Asp396 (M30 neoantigen), and the concentration of 20S proteasome. Serum levels of the CK-18 neoepitope M30 were significantly increased in ALF, primary graft dysfunction, and liver cirrhosis vs. healthy controls (1,993.6+/-124.7 U/L, 2,238.1+/-235.9 U/L, and 673.6+/-86.5 U/L vs. 66.8+/-29.1 U/L, respectively, P<0.001). Similar results were detected with the evaluation of 20S proteasome (124,014.5+/-13,235.6 ng/mL, 76,993.2+/-15,720.1 ng/mL, and 2,395.9+/-1,098.2 ng/mL vs. 1,074.5+/-259.4 ng/mL, respectively; P<0.001). Detection of CK-18 neoepitope M30 and 20S proteasome may represent a novel marker of tracing apoptotic epithelium, respectively mirroring degenerative liver processes in affected patient population.     

FIB-4预测慢性肝病患者肝细胞癌风险的meta分析

目的 系统评价FIB-4预测慢性肝病患者出现肝细胞癌的价值。方法 检索PubMed、Web of Science、中国知网和万方数据库中有关FIB-4预测慢性肝病患者肝细胞癌风险的文献,并根据纳入和排除标准筛选,利用RevMan 5.3软件进行统计分析。结果 共纳入文献35篇,包含肝细胞癌患者94 569例。Meta分析结果显示：慢性肝病患者基线高FIB-4(HR=1.57, 95%CI:1.41-1.75,P<0.01)及抗病毒治疗后高FIB-4(HR=2.40, 95%CI:1.74-3.32,P<0.01)与慢性乙肝或慢性丙肝患者的高肝细胞癌风险有关。结论 FIB-4可预测慢性肝病患者的肝细胞癌风险。     

Relationship between tumor necrosis factor-alpha and ammonia in patients with hepatic encephalopathy due to chronic liver failure

BACKGROUND: We have recently demonstrated that in humans, circulating levels of tumor necrosis factor-alpha (TNF) correlate positively with severity of hepatic encephalopathy (HE) due to chronic liver failure.AIM. The main aim of this larger population study is to determine the relationship between TNF and ammonia in patients with HE and chronic liver failure due to liver cirrhosis. METHODS: Circulating levels of TNF and ammonia were measured in 108 patients with liver cirrhosis due to various etiologies in various clinical grades of HE (grades 0-4). TNF concentrations were measured in venous serum using commercially available solid-phase high sensitivity enzyme-linked immunosorbent assay. Ammonia levels were determined in venous plasma by the enzymatic method, using the glutamate dehydrogenase reaction. RESULTS: The mean+/-SEM values of circulating levels of TNF and ammonia at presentation in patients with grade 0 of HE (n = 30) were 3.89+/-0.2 pg/mL and 49.8+/-2.8 microg/mL respectively, in patients with grade 1 of HE (n = 26) were 8.56+/-0.34 pg/mL and 101.6+/-6.5 microg/mL respectively, in patients with grade 2 of HE (n = 22) were 11.59+/-0.48 pg/mL and 160.3+/-10.7 microg/mL respectively, in patients with grade 3 of HE (n = 20) were 19.98+/-0.94 pg/mL and 228.8+/-16.1 microg/mL respectively, and in patients with grade 4 of HE (n = 10) were 51.53+/-8.59 pg/mL and 284.2+/-20.3 microg/mL respectively. A significant positive correlation was found between circulating levels of TNF and those of ammonia (r = 0.62, P< 0.0001), and also between circulating levels of both substances and severity of HE in these patients (r = 0.95, P<0.0001, and r = 0.9, P<0.0001 respectively). TNF and ammonia were both significant independent predictors of severity of HE (P<0.0001 for both variables). CONCLUSION: The results of this study demonstrate a significant relationship between TNF and ammonia in patients with chronic liver failure and HE, and so strengthen the suggestion that TNF could be strongly involved in the pathogenesis of HE in these patients. Hence, we suggest a new theory in the pathogenesis of HE, the "TNF theory".     

Serum protein oxidation in patients with rheumatoid arthritis and effects of infliximab therapy

OBJECTIVE: To examine protein oxidation in rheumatoid arthritis (RA) and evaluate its evolution after infliximab therapy in a subgroup of patients. METHODS: Seventy-one consecutive patients with RA were included. Among them, 30 patients refractory to conventional therapy were treated with infliximab. Serum markers of oxidative stress were determined at baseline and before the infusions of infliximab at weeks 6 and 30. Baseline values were compared with those in 30 healthy volunteers. RESULTS: Mean levels of serum carbonyl groups were significantly higher in RA patients than in controls (1.29+/-0.76 versus 0.58+/-0.39 nmol/mg of protein, p<0.0001), whereas thiol levels were found to be lower (238.3+/-61.6 versus 316.5+/-54.8 micromol/L, p<0.0001). Thiol levels inversely correlated with the disease activity score (r=-0.42, p=0.004), and with CRP values (r=-0.45, p=0.001). Immunoblots showed that albumin and heavy chain immunoglobulin were oxidized more markedly than in healthy volunteers. Significantly lower levels of thiol groups were detected in patients with refractory RA disease (208.9+/-66.8 versus 264.2+/-43.0 micromol/L, p<0.0004) but concentrations of carbonyl groups were similar. Short-term treatment with infliximab significantly decreased carbonyl groups (0.97+/-0.47 nmol/mg protein, p=0.02) and increased thiol (231.2+/-48.7 micromol/L, p=0.02) levels. CONCLUSION: Our results highlight free radical protein damage in RA and a link with inflammation, as underlined by the beneficial effects of infliximab.     

Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure

Summary. Background: It has been well established that hemostatic potential in patients with chronic liver disease is in a rebalanced status due to a concomitant decrease in pro‐ and antihemostatic drivers. The hemostatic changes in patients with acute liver injury/failure (ALI/ALF) are similar but not identical to the changes in patients with chronic liver disease and have not been studied in great detail. Objective: To assess thrombin generation and fibrinolytic potential in patients with ALI/ALF. Methods: We performed thrombin generation tests and clot lysis assays in platelet‐poor plasma from 50 patients with ALI/ALF. Results were compared with values obtained in plasma from 40 healthy volunteers. Results and conclusion: The thrombin generation capacity of plasma from patients with ALI/ALF sampled on the day of admission to hospital was indistinguishable from that of healthy controls, provided thrombomodulin was added to the test mixture. Fibrinolytic capacity was profoundly impaired in patients with ALI/ALF on admission (no lysis in 73.5% of patients, compared with 2.5% of the healthy controls), which was associated with decreased levels of the plasminogen and increased levels of plasminogen activator inhibitor type 1. The intact thrombin generating capacity and the hypofibrinolytic status persisted during the first week of admission. Patients with ALI/ALF have a normal thrombin generating capacity and a decreased capacity to remove fibrin clots. These results contrast with routine laboratory tests such as the PT/INR, which are by definition prolonged in patients with ALI/ALF and suggest a bleeding tendency.     

Hyperhomocysteinemia is associated with deep venous thrombosis of the lower extremities in Tunisian patients

OBJECTIVES: To test the association between hyperhomocysteinemia (HHC) and deep venous thrombosis (DVT) of lower extremities in Tunisians. DESIGN AND METHODS: This case-control study included 90 patients with DVT of the lower extremities and 160 healthy controls. Plasma homocysteine, vitamin B(12) and folate were determined using immunoenzymatic methods. Logistic regression models were performed to test whether the association between HHC and DVT is independent and to precise determinants of HHC in DVT patients. RESULTS: Plasma total homocysteine concentrations were significantly higher in patients with DVT (17.4+/-11.5 micromol/L) and in patients with idiopathic DVT (15.2+/-6.4 micromol/L) as compared to controls (11.5+/-3.3 micromol/L). HHC was significantly associated (p<0.001) with all DVT (OR, 8.82; 95% CI, 3.96-19.6) as well as idiopathic DVT (OR, 7.40; 95% CI, 3.01-10.8). These associations persisted after adjustment for several thrombosis risk factors. In patients with DVT, HHC was related to folate and vitamin B(12) concentrations, but neither to the type of occurrence nor to the recurrence of DVT. CONCLUSION: HHC is independently associated with first DVT of lower extremities in Tunisians. Homocysteine should be assessed in patients with DVT and the effect of vitamin B supplementation should be tested among them.     

肝移植术后危重患者血浆脂质过氧化物的变化及意义

目的　研究肝移植患者术后血浆中脂质过氧化物 (L PO)与术后病情变化的关系。方法　测定了18例肝移植患者术后 2 1d内血浆中 L PO的水平 ,分析其与预后的关系。结果　血浆 L PO在病情明显恶化前有所升高 ,尤其在死亡组患者持续升高 ,其升高的峰值明显高于存活患者 ,血浆 L PO峰值超过 10 μmol/L 的患者死亡几率 (5 /6 )高于血浆 L PO峰值低于 10 μmol/L 的患者 (1/12 ) ,两组病死率差异有显著性意义(P<0 .0 1) ,血浆 L PO日变化率超过 1.2 μmol· L- 1· d- 1的患者死亡几率 (4/5 )高于血浆 L PO日变化率低于 1.2 μmol· L- 1· d- 1的患者 (2 /13) ,两组病死率差异有显著性意义 (P<0 .0 1)。结论　术后检测血浆 L PO对正确判断患者病情危重程度有重要的临床价值 ,可作为常规检查。     

血浆置换联合高通量血液透析滤过治疗重症肝炎肝脏衰竭临床研究

目的 :探讨非生物型人工肝支持疗法血浆置换 (PE)与高通量血液透析滤过 (HDF)相结合对国内重症肝炎肝脏衰竭的临床疗效、安全性及可行性。方法 :对 2 6例不同病因重症肝炎肝衰竭患者应用上述人工肝方法进行治疗 5 8次 ,通过比较治疗前后患者临床症状、肝功能、凝血酶原活动度 (PTA)、血氨等指标判断临床疗效 ,观察治疗相关的不良反应及患者耐受情况判断安全性及可行性。结果 :患者意识、黄疸、乏力、腹胀、纳差等症状均明显缓解 ,血清总胆红素治疗后较治疗前平均降低 (190 .8± 93.6 )μmol/L ,PTA上升 (19.7± 8.9) % ,治疗后存活率达 80 .8% ,不良反应主要以血浆过敏居多 ,未发生大出血、休克等严重并发症及应用血制品引起的重叠感染 ,患者耐受良好。结论 :PE联合 HDF可显著改善重症肝炎肝脏功能衰竭患者临床症状及生化指标 ,提高近期存活率 ,且安全可行 ,值得在国内推广使用。     

Elevated apoptosis-associated cytokeratin 18 fragments (CK18Asp386) in serum of patients with chronic liver diseases indicate hepatic and biliary inflammation

OBJECTIVES: During apoptosis, intermediate filament protein cytokeratin 18 (CK18) is cleaved by caspases at Asp396 which can be specifically detected by the monoclonal antibody M30 (M30-antigen). DESIGN AND METHODS: M30-antigen serum levels were analyzed in 76 chronic liver diseases (CLD) patients and 62 healthy controls. RESULTS: M30-antigen levels were significantly elevated in CLD patients (median 296.3 U/L) compared with healthy controls (median 153.5 U/L, P<0.001) and increased with disease severity (Child-Pugh or MELD score). M30-antigen correlated with aminotransferase activities and parameters indicating cholestasis such as bile acids. Highest serum M30-antigen was associated with histologically confirmed severe intrahepatic cholestasis (median 599.1 U/L) or biliary duct inflammation (median 648.0 U/L). Furthermore, in contrast to patients with liver cirrhosis, presence of hepatocellular carcinoma was associated with elevated M30-antigen in patients without cirrhosis. CONCLUSION: Serum M30-antigen levels are elevated in CLD and correlate with hepatic inflammation as well as cholangitis and cholestasis.     

Basal and post-methionine serum homocysteine and lipoprotein abnormalities in patients with chronic liver disease.

BACKGROUND: Lipoprotein abnormalities are commonly found in chronic liver diseases (CLDs), particularly hypercholesterolemia in primary biliary cirrhosis (PBC). However, affected patients may not be at increased risk of coronary heart disease. Cirrhotic patients display impaired methionine clearance, and an increased level of homocysteine, a methionine metabolite, is an independent risk factor for coronary heart disease. Thus, we hypothesized that the low risk of coronary heart disease in patients with CLD may be related to low serum levels of homocysteine. The aim of this study was to test this hypothesis after methionine load and to describe the serum lipoprotein profile in patients with PBC and in patients with hepatocellular liver disease. METHODS: Fifteen female patients (mean age, 58.2 +/- 11.7 years) with PBC, 15 female patients (mean age, 54.5 +/- 9.6 years) with other causes of CLD, and 15 healthy sex- and age-matched controls were given L-methionine (50 mg/kg of ideal body weight). Basal fasting serum homocysteine level and 2, 4, and 6 hours of post-methionine load were determined using high-performance liquid chromatography with a fluorometric detector. Levels of fasting serum cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), lipoprotein (a) (Lp(a)), and apoprotein B were also determined. RESULTS: Results showed that mean basal and post-methionine load (6 hours) serum homocysteine levels were statistically significantly higher in the patients with PBC and with CLD than in the control group (P=0.04) and that levels of serum cholesterol, LDL, HDL, and apoprotein B were significantly higher in the PBC patients than in the other two groups (P < or = 0.05). There was no correlation between any of these parameters and the severity of liver disease. Serum HDL was significantly lower in the CLD group (P < or = 0.05) and correlated with severity of liver disease. There was no significant difference in serum cholesterol, LDL, or apoprotein B between the CLD group and the controls. Serum triglyceride and Lp(a) levels were similar for all three groups. CONCLUSIONS: In contrast to previous reports, the site of the methionine metabolic impairment was found to be below the homocysteine synthesis level. For most patients with CLD, factors other than serum homocysteine or Lp(a) are responsible for the reduction in the risk of coronary heart disease. Further studies with larger samples are needed.     

Renin, aldosterone and arginine vasopressin in patients with liver cirrhosis: the influence of ascites retransfusion

Plasma renin activity (PRA), and concentrations of aldosterone (PAL) and arginine vasopressin (AVP) in plasma were determined in 15 patients with ascites due to cirrhosis. The concentrations in ascites were analyzed simultaneously. Six patients were studied during extracorporeal ascites retransfusion. All but one patient with ascites showed elevated PAL (642 +/- 255 pg ml-1) and PRA (43 +/- 26 ng ml-1 h-1); all had increased AVP (7.3 +/- 5.1 pg ml-1). A low ascites to plasma ratio was found for aldosterone (0.023 +/- 0.023), but not for AVP (0.71 +/- 0.82). Retransfusion resulted in a normalization of central venous pressure (CVP), urinary volume, sodium/potassium ratio in urine, PAL and PRA, but not of AVP, serum sodium concentration and urinary sodium excretion. PRA and PAL increased again after cessation of treatment, while urinary output, CVP and sodium/potassium ratio in urine decreased. The results support the 'underfilling' concept, but give evidence that, in addition, other factors must be involved in the impaired natriuresis in cirrhotic patients. They further support the concept of volume expansion and increased renal perfusion as reason for the therapeutic efficacy of ascites retransfusion. Previous diuretic treatment seems not to be of importance for altered hormone metabolism in liver cirrhosis. Storage in a third compartment may be a factor in the persistently elevated AVP levels.     

Elevated levels of plasma homocysteine in postmenopausal women in Burkina Faso.

BACKGROUND: Low levels of plasma homocysteine have been found in children and adult populations living in Burkina Faso in association with a low prevalence of coronary heart disease. METHODS: Based on this finding, the levels of plasma homocysteine and other thiols (cysteine, cysteinylglycine, glutathione) in postmenopausal women living in Burkina Faso were evaluated with the aim of investigating whether age and life conditions influence plasma homocysteine and other thiol levels. RESULTS: It was found that in older postmenopausal women the mean level of homocysteine was higher (16.4+/-6.6 micromol/L) than in fertile women (6.8+/-1.2 micromol/L) and that this increase was correlated with cysteine levels (166.6+/-44.6 micromol/L). While the glutathione level in postmenopausal women was lower (3.6+/-2.3 micromol/L) compared with fertile women (7.0+/-1.7 micromol/L), cysteinylglycine levels were within the normal range (29.9+/-9.3 micromol/L). No correlation was found between homocysteine levels and serum folate, vitamin B(12), vitamin B(6), cystatin C and serum creatinine levels. The older the women were, the higher were their plasma homocysteine levels: levels up to 20.2+/-9.1 micromol/L were found in those >70 years old. CONCLUSIONS: The elevated levels of homocysteine in the postmenopausal women of Burkina Faso must be viewed as a characteristic of older age and its metabolic consequences.     

Erythrocyte membrane Na+,K+-ATPase and Mg2+-ATPase activities in subjects with methylenetetrahydrofolate reductase (MTHFR) 677 C-->T genotype and moderate hyperhomocysteinaemia. The role of L-phenylalanine and L-alanine.

BACKGROUND: Increased homocysteine (Hcy) blood levels are correlated with vascular and neurological problems. The aim of our study was to investigate erythrocyte membrane Na(+),K(+)-ATPase and Mg(2+)-ATPase activities in patients with methylenetetrahydrofolate reductase (MTHFR) 677 C-->T genotype. METHODS: Blood was obtained from 25 patients before and after folic acid supplementation and from controls (n=30) once. Plasma folate, vitamin B(12) and total antioxidant status (TAS) were measured using commercial kits, Hcy was determined by HPLC and membrane enzyme activities were measured spectrophotometrically. RESULTS: Mg(2+)-ATPase remained unaltered. Membrane Na(+),K(+)-ATPase activity was remarkably increased in patients (0.77+/-0.06 micromol Pi/h x mg protein) and decreased to normal levels (0.52+/-0.05 micromol Pi/h x mg protein; p<0.001) after therapy. TAS did not differ significantly before and after treatment. Hcy levels were significantly higher before therapy (25.4+/-2.8 micromol/L) than levels after therapy (12.1+/-2.0 micromol/L; p<0.001) and in controls (10.5+/-2.5 micromol/L, p<0.001). In vitro, L-phenylalanine (Phe) reversed to normal the stimulated enzyme from patients before therapy. In addition, Phe incubation of the Hcy activated membrane Na(+),K(+)-ATPase from controls resulted in restoration of its activity, whereas L-alanine (Ala) incubation protected the enzyme from Hcy activation. CONCLUSIONS: The increased membrane Na(+),K(+)-ATPase activity may be due to high -SH group Hcy levels. In vitro, Phe reversed the increase in enzyme activity induced by Hcy in controls, as well as the stimulated membrane enzyme in untreated patients. Ala protected the enzyme from Hcy action.     

Low total antioxidant status is implicated with high 8-hydroxy-2-deoxyguanosine serum concentrations in phenylketonuria

BACKGROUND: Phenylketonuria (PKU), an inborn error of metabolism, is treated with a low phenylalanine (Phe) lifelong diet, which can be characterized as vegetarian. 8-Hydroxy-2-deoxyguanosine (8-OHdG) is highly implicated in degenerative diseases. OBJECTIVE: To evaluate the effect of plasma total antioxidant status (TAS) and Phe on the serum marker of DNA damage, 8-OHdG, in PKU. METHODS: Twenty-four PKU patients on a strict diet (group A), 25 PKU patients on a "loose diet" (group B), and 24 healthy children (controls) participated in this study. Plasma TAS was evaluated spectrophotometrically. 8-OHdG and Phe were measured in blood with immunoassays. RESULTS: TAS levels were significantly higher (P < 0.001) in group A (1458 +/- 140 micromol/L) and controls (1452 +/- 235 micromol/L) than those in group B (907 +/- 150 micromol/L). In contrast, 8-OHdG serum levels were 2-fold higher in group B (0.22 +/- 0.03 ng/mL) as compared with those in group A (0.11 +/- 0.02 ng/mL) and 3-fold higher than those in controls (0.08 +/- 0.02 ng/mL) (P < 0.001). As expected, Phe levels were also significantly higher in group B than those in the other study groups. Positive correlation coefficients were found between Phe and 8-OHdG levels, whereas negative correlations were evaluated between TAS and 8-OHdG in all groups. CONCLUSIONS: The high Phe and the low TAS plasma levels in PKU patients on a "loose diet" may induce DNA oxidation, as evidenced by the measured high 8-OHdG level in their sera. 8-OHdG evaluation may be a useful marker of increased risk for a neurodegenerative process.