Effect of vitamin E on serum aminotransferase and thioredoxin levels in patients with viral hepatitis C

OBJECTIVES: Oxidative stress induces cellular responses such as cell death, gene activation and cell proliferation, in the liver. Vitamin E (Vit. E) has been found to protect the liver against oxidative stress in animal experiments. Thioredoxin (TRX) is a stress inducible, multifunctional protein, secreted during oxidative stress. This study evaluated effects of Vit. E on serum TRX and aminotransferase levels in hepatitis C virus (HCV) patients, partly non-responsive to initial interferon (IFN), with higher than average level of serum alanine aminotransferase (ALT) after receiving anti-inflammatory drug treatment. METHODS: Seventeen HCV patients (male = 3; female = 14) of age 62 +/- 7.65 years receiving anti-inflammatory drug therapy, at least 6 months prior to Vit. E administration, were given d-alpha-tocopherol 500 mg/day, orally, for a period of 3 months. ALT, aspartate aminotransferase (AST), TRX and Vit. E were measured at 0, 1, 2 and 3 months and 1 month after end of treatment. As controls, the same patients biochemical data, 3 months from the start of therapy were used. Patients were divided into three categories: total patients "T", low ALT group "L" (ALT < 70 IU/l) and high ALT group "H" (ALT > 70 IU/l), respectively. RESULTS: The ALT level was lowered, significantly in group H, in the 1st, 2nd, 3rd and 1-month post therapy, compared to the initial value. But group L showed little or no change in ALT. Post Vit. E therapy, in groups T and H, the TRX level was elevated but remained below initial levels, whereas in group L, TRX level remained significantly lower than the pretreatment value. Groups T and L, showed significant reduction (p < 0.05) in serum TRX levels in the 2nd and 3rd month. Group H showed a tendency towards TRX reduction, but not significantly. Serum Vit. E levels increased significantly (p < 0.0001) from the 1st to 3rd month in all three T, H and L groups. CONCLUSION: Oxidative stress induced liver damage is reduced by Vit. E in patients with viral hepatitis C, particularly those with initial ALT levels > 70 IU/l. Vit. E treatment causes reduction of oxidative stress markers as TRX and ALT in sera. Therefore, Vit. E can act as a supportive therapy to combat liver damage caused by oxidative stress, in such patients with continuously high levels of ALT even after anti-viral and anti-inflammatory drug therapy.     

Effect of Vitamin E on Serum Aminotransferase and Thioredoxin Levels in Patients with Viral Hepatitis C

Objectives: Oxidative stress induces cellular responses such as cell death, gene activation and cell proliferation, in the liver. Vitamin E (Vit. E) has been found to protect the liver against oxidative stress in animal experiments. Thioredoxin (TRX) is a stress inducible, multifunctional protein, secreted during oxidative stress. This study evaluated effects of Vit. E on serum TRX and aminotransferase levels in hepatitis C virus (HCV) patients, partly non-responsive to initial interferon (IFN), with higher than average level of serum alanine aminotransferase (ALT) after receiving anti-inflammatory drug treatment. Methods: Seventeen HCV patients (male=3; female=14) of age 62±7.65 years receiving anti-inflammatory drug therapy, at least 6 months prior to Vit. E administration, were given d-α´-tocopherol 500?mg/day, orally, for a period of 3 months. ALT, aspartate aminotransferase (AST), TRX and Vit. E were measured at 0, 1, 2 and 3 months and 1 month after end of treatment. As controls, the same patients biochemical data, 3 months from the start of therapy were used. Patients were divided into three categories: total patients “T”, low ALT group “L” (ALT<70?IU/l) and high ALT group “H”(ALT>70?IU/l), respectively.Results: The ALT level was lowered, significantly in group H, in the 1st, 2nd, 3rd and 1-month post therapy, compared to the initial value. But group L showed little or no change in ALT. Post Vit. E therapy, in groups T and H, the TRX level was elevated but remained below initial levels, whereas in group L, TRX level remained significantly lower than the pretreatment value. Groups T and L, showed significant reduction (p<0.05) in serum TRX levels in the 2nd and 3rd month. Group H showed a tendency towards TRX reduction, but not significantly. Serum Vit. E levels increased significantly (p<0.0001) from the 1st to 3rd month in all three T, H and L groups. Conclusion: Oxidative stress induced liver damage is reduced by Vit. E in patients with viral hepatitis C, particularly those with initial ALT levels >70?IU/l. Vit. E treatment causes reduction of oxidative stress markers as TRX and ALT in sera. Therefore, Vit. E can act as a supportive therapy to combat liver damage caused by oxidative stress, in such patients with continuously high levels of ALT even after anti-viral and anti-inflammatory drug therapy.     

Dietary amino acid taurine ameliorates liver injury in chronic hepatitis patients

The effect of dietary amino acid taurine on the liver function of chronic hepatitis patients was investigated. The 24 chronic hepatitis patients with 2-5 times over normal activities of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) were selected and equally divided into taurine treatment and control groups. In taurine treatment group, each patient took 2 g taurine 3 times a day for three months, and then stopped treatment for 1 month. Patients taking placebo without taurine for 4 months served as a control group. ALT and AST activities and levels of cholesterol, triglyceride and thiobarbituric acid relative substances of serum plasma in the taurine group were all decreased at the end of three month treatment. The study suggested that dietary amino acid taurine may ameliorate liver injury for chronic hepatitis patients.     

The effect of vitamin E supplementation on reduction of lymphocyte DNA damage induced by T-2 toxin and deoxynivalenol in weaned pigs

The objective of the present study was to establish the effect of deoxynivalenol (DON) and T-2 toxin on lipid peroxidation, lymphocyte DNA fragmentation and immunoglobulin production in weaned pigs, and furthermore, to evaluate the potential of vitamin E (α-tocopheryl acetate) in prevention of toxin mediated changes. Forty-eight weaned castrated male crossbred pigs (mean live weight at the beginning of the experimental period was 11.7 kg) were randomly assigned to five experimental groups: control (without toxin and vitamin E), T-2 (3 mg/kg T-2 toxin), T-2 + E (3 mg/kg T-2 toxin + 100 mg/kg vitamin E), DON (4 mg/kg DON) and DON + E (4 mg/kg DON + 100 mg/kg vitamin E). After 14 days of treatment blood was collected for analysis. Lipid peroxidation was studied by assays of malondialdehyde (MDA), total antioxidant status (TAS) of plasma and erythrocyte glutathione peroxidase (GPx). DNA damage in lymphocytes was measured by comet assay. Serum immunoglobulin levels were evaluated by enzyme-linked immunosorbent assay (ELISA) and the hepatotoxicity was studied by measuring plasma liver enzyme levels (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl-transferase (GGT). Production parameters of both DON groups were significantly impaired in comparison to the control. DON significantly increased the amount of DNA damage in lymphocytes by 28%. Moreover, the levels of TAS were lowered by addition of DON. T-2 toxin significantly impaired daily live weight gain and feed conversion, increased the amount of DNA damage in lymphocytes by 27%, decreased total serum IgG and did not alter plasma TAS. Plasma and 24-h urinary malondialdehyde (MDA) excretion rate and erythrocyte Gpx levels did not differ among the groups. Supplementation with vitamin E did not improve production parameters impaired by DON and T-2 toxin and only partially protected lymphocyte DNA from toxin impact. To our knowledge, these are the first data on genotoxic effects of moderate doses of DON and T-2 toxin on pig lymphocytes. The effect of DON and T-2 toxin on the immune system was reflected as a change in immunoglobulin synthesis, which might be toxin and species specific. According to other results no major induction of oxidative stress could be proven. Enhancement of antioxidant status with vitamin E in the case of DON and T-2 toxin intoxication can be beneficial for remaining the lymphocyte DNA integrity.     

Comparison of Histologic Characteristics of Chinese Chronic Hepatitis B Patients with Persistently Normal or Mildly Elevated ALT

Liver disease can develop in chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT) who seldom undergo liver biopsy. We aimed to determine histologic characteristics of a large cohort of Chinese CHB patients undergoing liver biopsy and to evaluate the utility of ALT and HBV DNA values at the time of biopsy in predicting liver disease in this population. This prospective study enrolled 230 treatment-naïve patients with persistently normal or mildly elevated ALT. All patients had a liver biopsy. ALT, aspartate aminotransferase (AST), and HBV DNA levels were some of the other parameters measured. Using Scheuer''s classification, significant histology was defined as stage ≧2 fibrosis and/or stage 1 fibrosis plus≧ grade 2 inflammation. Liver disease was observed in 34.4% and 61.8% of patients with normal ALT and mildly elevated ALT, respectively. Patients with mildly elevated ALT levels had significantly more events, including liver disease, elevated AST, and moderate to severe inflammation and liver fibrosis, than patients with normal ALT (all P≤0.005). A total of 107 patients (46.5%) had liver disease and 123 (53.5%) did not. PLT and ALT were significantly associated with liver disease (both P<0.001). Patients with elevated ALT, lower platelet count and HBV DNA < 7 log₁₀copies/mL may have histologically significant changes associated with liver disease. Multivariate analysis showed that PLT and HBV DNA levels were significantly associated with liver disease in patients with normal ALT while gender and HBV DNA levels were significantly associated with liver disease in patients with mildly elevated ALT. Assessing liver damage via biopsy in patients with normal or mildly elevated ALT may help to identify those who would benefit from antiviral therapy.     

Effects of β‐carotene on antioxidant status in rats with chronic alcohol consumption

This study examined the effects of β‐carotene on antioxidant status in rats with chronic alcohol consumption. At the beginning of experiment (week 0), according to both the plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, rats (n = 24) were divided into 3 groups and fed with a standard diet (group C), a diet containing ethanol (group E), or a diet containing ethanol and β‐carotene (group E+B). After 10 weeks, plasma AST and ALT, fat accumulation in the liver, antioxidant enzyme activities in erythrocytes and the liver, malondialdehyde (MDA), and α‐tocopherol and retinol in plasma and hepatic samples were analyzed. The chronic alcohol diet significantly increased AST and ALT levels in plasma, and these changes were prevented by supplementing the diet with β‐carotene. Glutathione (GSH) in erythrocytes and in the liver was significantly elevated in rats fed with a diet containing β‐carotene. The results indicate that β‐carotene supplementation can prevent ethanol‐induced liver damage and increase GSH concentrations in erythrocytes and the liver. Copyright © 2009 John Wiley & Sons, Ltd.     

Glucocerebroside treatment ameliorates ConA hepatitis by inhibition of NKT lymphocytes

Concanavalin A (ConA) induces natural killer T (NKT) cell-mediated liver damage. Glucocerebroside (GC) is a naturally occurring glycolipid. Our aims were to determine the effect of GC in a murine model of ConA-induced hepatitis. Mice in groups A and B were treated with GC 2 h before and 2 h following administration of ConA, respectively; group C mice were treated with ConA; group D mice was treated with GC; group E mice did not receive any treatment. Liver damage was evaluated by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver histology. The immune effect of GC was determined by fluorescence-activated cell sorter analysis of intrahepatic and intrasplenic NKT lymphocytes, measurement of cytokine levels, and Western blot analysis for STAT 1, 4, 6, and NF-kappaB expression. The effect of GC on NKT cell proliferation was assessed in vitro. Serum AST and ALT levels were markedly reduced in GC-treated group A mice compared with nontreated group C animals, and histological damage was markedly attenuated in group A. The beneficial effect of GC was associated with a 20% decrease of intrahepatic NKT lymphocytes, significant lowering of serum IFN-gamma levels, and decreased STAT1 and STAT6 expression. In vitro administration of GC led to a 42% decrease of NKT cell proliferation in the presence of dendritic cells but not in their absence. Intraperitoneally administered radioactive GC was detected in the liver and bowel. Administration of GC led to amelioration of ConA hepatitis associated with an inhibitory effect on NKT lymphocytes. GC holds promise as a new immune-modulatory agent.     

Serum alanine aminotransferase to aspartate aminotransferase ratio and degree of fatty liver in morbidly obese patients

We evaluated the change in serum alanine aminotransferase (ALT; EC 2.6.1.2) to serum aspartate aminotransferase (AST; EC 2.6.1.; ALT/AST) ratio with the degree of fatty liver in morbidly obese patients. A total of 31 patients were included in the study. Fatty liver was graded as 0 to 4+. The mean and SD of AST and ALT were not significantly different between groups of patients with various grades of fatty liver. There was, however, a significant correlation between the ALT/AST ratio and the degree of fatty infiltration of the liver. This, we believe, implies damage mainly to the plasma membrane allowing loss of cytoplasmic enzymes rather than loss of mitochondrial enzymes.     

新疆维吾尔族与汉族乙型肝炎患者HBVDNA 及肝功能检测结果的比较

目的:探讨新疆乌鲁木齐地区伴有肝功能指标:丙氨酸氨基转移酶(ALT)浓度异常的维吾尔族(维族)及汉族HBeAg阳性乙型肝炎初次就诊患者,乙型肝炎病毒DNA复制载量及ALT浓度是否存在差异及其对患者诊断、预后的意义。方法:回顾性选取门诊伴有ALT浓度异常的汉族、维族初次就诊患者并筛选出HBeAg阳性患者汉族、维族共373例。采用实时荧光定量聚合酶链反应、生化测定及酶联免疫吸附试验法分别测定HBV DNA、ALT浓度及乙肝HBeAg。结果:(1)汉族HBV DNA组秩和8869,维族HBV DNA组秩和10359.36,经Mann-Whitney Test检验两组间尚不能肯定HBVDNA分布有统计学意义,即伴有肝功能损害的汉族、维族初次就诊HBeAg阳性患者HBV DNA复制程度没有差异。(2)汉族ALT组秩和26818.50,维族ALT组秩和22009.50,经Mann-Whitney Test检验两组间ALT分布有统计学意义,即伴有肝功能损害的初次就诊HBeAg阳性患者汉族肝功能损害程度高于维族。(3)HBVDNA低复制组(103-104copy/mL):汉族秩和3771.46,维族秩和4993.2;中复制组(104-106copy/mL):汉族秩和6412.4,维族秩和5088.2;高复制组(>106copy/mL):汉族秩和929.04,维族秩和666.96,经Mann-Whitney Test检验在低复制组两民族间ALT分布无统计学意义,在中、高复制组两民族间ALT具有统计学意义。即:伴有肝功能损害的初次就诊HBeAg阳性患者在HBV DNA低复制组两民族间肝功能损害程度无差异,但在中、高复制组汉族肝功能损害程度高于维族。结论:新疆乌鲁木齐地区伴有肝功能损害的初次就诊的HBeAg阳性的汉族与维族之间HBV DNA的病毒复制无统计学意义(P>0.05),但两民族间的ALT具有统计学意义,可能跟维族的民俗、饮食习惯及生存环境、免疫相关基因HLA基因频率分布差异等因素有关。     

Evaluation of miR-122 level in the plasma of chronically HCV infected patients

MicroRNAs (miRNAs) are small non-coding RNA molecules, which have an important function in regulating RNA stability and gene expression. They also can circulate in a cell-free form in the blood thatmakes them potential disease markers. The liver contains various classes of miRNAs in which miR-122 accounts for about 70% of all miRNAs and it has been proved that its level increases in case of liver damage. Here, we investigated plasma levels of miR-122 as a useful disease parameter in patients with chronic hepatitis C (CHC) infection. Thirty five hemophilia and thalassemia patients with CHC were studied. The total RNA was extracted from plasma samples, and miR-122 levels were measured by qPCR and then compared with the specific liver markers. The plasma levels of alanine transaminase (ALT) and aspartate transaminase(AST) were correlated with plasma miR-122 level in CHC patients, and the level of circulating miR-122 in healthy individual groups were rarely lower than those of patients with CHC. In our study, miR-122 levels correlated well with markers of liver inflammatory activity. Plasma miR-122 can be assumed to be another marker in liver similar to the currently used specific markers such as ALT and AST for evaluation of liver damage in hepatitis C virus (HCV) infected patients. Moreover, the correlation between miR-122 and ALT was shown to be higher than between miR-122 and AST.     

Changes in serological biomarkers of liver function and connective tissue turnover in chronic hepatitis B during lamivudine therapy

Abstract

Assessment of hepatic damage associated with chronic hepatitis B (CHB) currently relies on measurement of serum transaminases and assessment of hepatic histology. It was determined serum hepatic function tests and the liver fibrosis biomarkers type IV collagen (CIV), amino-terminal propeptide of type I procollagen (PINP), amino-terminal propeptide of type III procollagen (PIIINP) and carboxy-terminal telopeptide of type I collagen (ICTP) were of value in monitoring the effect of lamivudine therapy for CHB. Thirty-nine patients received orally 100?mg lamivudine daily for 48 weeks. Blood samples were obtained at baseline, 24 and 48 weeks. At the end of the treatment period, the patients were then divided into four groups according to the pattern of HBs and HBe antigens. At baseline, alanine aminotransferase, aspartate aminotransferase, PIIINP and the PINP/ICTP ratio and at 24 weeks alanine aminotransferase, aspartate aminotransferase and the PINP/ICTP ratio had lower values in the complete response compared with complete failure groups. Using receiver-operated curve analysis, only the PINP/ICTP ratio at baseline (area under the curve 0.806) and ALT and the PINP/ICTP ratio at 24?weeks (areas under the curve 0.803 and 0.776, respectively) had significant diagnostic ability in detecting responders. In conclusion, the PINP/ITCP ratio is sensitive and specific in detecting responders to treatment.     

Changes in serological biomarkers of liver function and connective tissue turnover in chronic hepatitis B during lamivudine therapy

Assessment of hepatic damage associated with chronic hepatitis B (CHB) currently relies on measurement of serum transaminases and assessment of hepatic histology. It was determined serum hepatic function tests and the liver fibrosis biomarkers type IV collagen (CIV), amino-terminal propeptide of type I procollagen (PINP), amino-terminal propeptide of type III procollagen (PIIINP) and carboxy-terminal telopeptide of type I collagen (ICTP) were of value in monitoring the effect of lamivudine therapy for CHB. Thirty-nine patients received orally 100 mg lamivudine daily for 48 weeks. Blood samples were obtained at baseline, 24 and 48 weeks. At the end of the treatment period, the patients were then divided into four groups according to the pattern of HBs and HBe antigens. At baseline, alanine aminotransferase, aspartate aminotransferase, PIIINP and the PINP/ICTP ratio and at 24 weeks alanine aminotransferase, aspartate aminotransferase and the PINP/ICTP ratio had lower values in the complete response compared with complete failure groups. Using receiver-operated curve analysis, only the PINP/ICTP ratio at baseline (area under the curve 0.806) and ALT and the PINP/ICTP ratio at 24 weeks (areas under the curve 0.803 and 0.776, respectively) had significant diagnostic ability in detecting responders. In conclusion, the PINP/ITCP ratio is sensitive and specific in detecting responders to treatment.     

前列腺素E1 联合糖皮质激素治疗药物性重症肝炎的临床效果*

目的:探讨前列腺素E1联合糖皮质激素治疗药物性重症肝炎的临床效果。方法:前瞻性研究我院药物性重症肝炎患者68例,随机分为实验组与对照组,每组34例。对照组患者给予糖皮质激素治疗,实验组患者给予糖皮质激素联合前列腺素E1治疗。观察并比较治疗前后两组患者血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)水平的变化情况,以及临床疗效和并发症的发生率。结果:与治疗前相比,两组患者治疗后血清ALT,AST,TBIL水平均降低,差异具有统计学意义(P0.05);与对照组相比,实验组患者治疗后血清ALT,AST及TBIL水平较低,差异具有统计学意义(P0.05);实验组患者并发症发生率(41.18%)明显低于对照组(52.94%),差异具有统计学意义(P0.05)。实验组患者临床总有效率(91.18%)显著高于对照组(73.53%),差异具有统计学意义(P0.05)。结论:前列腺素E1联合糖皮质激素能够提高药物性重症肝炎的临床总有效率,降低并发症发病率,值得在临床上推广应用。     

Effects of vitamin E on serum enzymes and electrolytes in hypercholesterolemia

It is not known if vitamin E in hyperlipidemia and hypercholesterolemia of longer duration has any beneficial or adverse effects on electrolytes, and liver and kidney function. The objectives of this study are to determine (i) if long duration of mild hypercholesterolemia has any adverse effects on serum electrolytes, glucose and enzymes related to liver and kidney functions; (ii) if vitamin E has any effects on serum electrolytes, glucose and enzymes related to liver and kidney function in hypercholesterolemia. Blood samples were collected from the rabbits before and at various intervals during administration of a high cholesterol diet (0.25%) for 2 and 4 months, and while on a high cholesterol diet with vitamin E following a high cholesterol diet. Measurements of serum total cholesterol (TC), glucose, aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), albumin, creatinine, electrolytes [sodium (Na), potassium (K), chloride (Cl), and carbon dioxide (CO₂)] were made. High cholesterol diet for 2 months produced hypercholesterolemia which was associated with reductions in serum glucose, unaltered serum electrolytes, ALT, ALP, GGT, albumin and creatinine, and increased levels of AST. Hypercholesterolemia for 4 months had effects similar to hypercholesterolemia for 2 months except it lowered serum ALP. Vitamin E did not affect any of the parameters except serum glucose and Cl, which decreased compared to the values at month 2. Hypercholesterolemia for short and long term does not have adverse effects on liver or kidney function, and serum electrolytes. Vitamin E during hypercholesterolemia does not affect serum electrolytes or liver and kidney function.     

Artichoke leave extract for chronic hepatitis C – A pilot study

BackgroundArtichoke leave extracts (ALE) have hepatoprotektive properties and are used by patients with chronic liver disease. Effects in patients with chronic hepatitis C are unclear.Methods17 patients with chronic hepatitis C and persistently elevated aminotransferase levels were treated for 12 weeks with 3200 mg standardized ALE per day. Primary outcome parameter was the rate of alanine aminotransferase (ALT) normalisation after 12 weeks. Secondary parameters were the course of ALT, aspartate aminotransferase and γ glutamyltransferase levels, quantitative HCV RNA, subjective symptoms frequently associated with chronic hepatitis C (fatigue, discomfort upper abdomen, joint problems) and safety.ResultsNone of the patients had normalized ALT levels after 12 weeks of treatment. There was no significant change of aminotransferase levels or viral load compared to baseline levels. Fatigue and joint problems significantly improved after 4 weeks of treatment. However, after 12 weeks, there was no significant difference to baseline. Tolerability of ALE was rated as good to excellent. Severe side effects did not occur.ConclusionALE seem not to be effective to improve aminotransferase levels in patients with chronic hepatitis C     

乙肝免疫标志物与乙肝病毒核酸含量与肝功能的关系研究

目的:研究乙肝免疫标记物(HBV-M)与乙肝病毒脱氧核苷酸(HBV-DNA)载量与肝功能的关系。方法:检测104例乙肝患者HBs Ag、HBe Ag、HBc Ab、HBs Ab、HBe Ab5种HBV-M;用PCR法检测HBV-DNA含量;同时检测天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、胆碱酯酶(CHE)等肝功能指标,对三者关系采用Spearman相关性分析。结果:HBs Ag、HBc Ab、HBe Ag阳性组HBV-DNA阳性率及载量均大于其余组(P0.05);HBe Ag含量、ALT浓度与HBV-DNA载量均呈正相关(r=0.48,P0.05)、(r=0.36,P0.05);AST、CHE与HBV-DNA含量无明显相关性,但在无病毒载量与有病毒载量组之间AST比较有统计学意义(P0.05)。结论:HBV-M、HBV-DNA与肝功能之间有一定的相关性,但HBe Ag阴转不代表病毒复制停止,HBV-DNA也不能完全反应肝损害程度,临床应加大重视。     

双歧杆菌四联活菌片联合乳果糖对乙肝肝硬化患者肠道菌群 和肠黏膜屏障功能及肝功能水平的影响

目的研究双歧杆菌四联活菌片联合乳果糖对乙肝肝硬化患者肠道菌群、肠黏膜屏障功能及肝功能水平的影响。方法选择2017年12月至2018年12月于我院感染科住院治疗的乙肝肝硬化患者80例,按照随机数字表法分为试验组和对照组各40例。两组患者常规予以抗病毒及保肝治疗。试验组患者加用双歧杆菌四联活菌片和乳果糖口服液。对照组患者仅给予乳果糖口服液。检测患者肠道肠杆菌、肠球菌、双歧杆菌、乳杆菌和白假丝酵母数量。测定患者血清内毒素和血清二胺氧化酶水平及尿乳果糖/甘露醇(L/M)比值。记录两组患者丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)和总胆红素(TBIL)水平。观察治疗过程中的药物不良反应发生情况。结果治疗4周后,试验组患者肠道肠球菌数量高于治疗1周后(18.41±2.92 vs 18.32±3.06),同时试验组患者肠道双歧杆菌数量与治疗前、治疗1周后以及对照组同时期相比差异也有统计学意义(均P0.05)。试验组患者治疗后肠道乳杆菌和白假丝酵母水平与治疗前相比差异均有统计学意义(均P0.05)。治疗4周后,对照组患者肠道肠杆菌水平高于治疗1周后(F=10.192,P=0.019);而白假丝酵母水平高于治疗前(F=8.567,P=0.024)。治疗前两组患者血清内毒素、血清二胺氧化酶和尿L/M以及AST、ALT、TBIL水平差异无统计学意义(均P0.05)。治疗1个月后,两组患者血清内毒素、血清二胺氧化酶和尿L/M以及AST、ALT、TBIL均较治疗前明显下降(均P0.05),且试验组的下降幅度较对照组更大(均P0.05)。两组患者均未发生不良反应。结论双歧杆菌四联活菌片联合乳果糖可以改善乙肝肝硬化患者肝功能状态,调节失衡的肠道菌群,降低肠黏膜通透性,值得临床推广。     

Diphenyl diselenide reverses cadmium-induced oxidative damage on mice tissues

The concept that selenium-containing molecules may be better antioxidants than classical antioxidants, has led to the design of synthetic organoselenium compounds. In the present investigation subchronic deleterious effects of cadmium-intoxication in mice and a possible protective effect of diphenyl diselenide (PhSe)2 (5 micromol/kg) were studied. Male adult Swiss albino mice (25-35 g) received CdCl2 (10 micromol/kg, subcutaneously), five times/week, for 4 weeks. A number of toxicological parameters in blood, liver, kidney, spleen and brain of mice were examined including delta-aminolevulinic acid dehydratase (delta-ALA-D) activity, lipid peroxidation and ascorbic acid content, the parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and lactate dehydrogenase (LDH) were also determined. The results demonstrated that cadmium caused inhibition of delta-ALA-D activity in liver (24%), kidney (33%) and spleen (73%) and (PhSe)2 therapy was effective in restoring enzyme activity in all tissues. A reduction in ascorbic acid content was observed in kidney (11%) and spleen (10.7%) of cadmium-treated mice and (PhSe)2 was only effective in improving this reduction in kidney. An increase of lipid peroxidation induced by cadmium was noted in liver (29%) and brain (28%) tissues and (PhSe)2 therapy was effective in restoring TBARS levels in both tissues. We also observed an increase on plasma LDH (1.99-times), AST (1.93-times) and ALT (4.24-times) activities. (PhSe)2 therapy was effective in restoring AST activity at control level. (PhSe)2 did not present toxic effects when plasma parameters were evaluated. The results suggest that the administration of an antioxidant (PhSe)2, during cadmium intoxication may provide beneficial effects by reducing oxidative stress in tissues.     

Effects of short-term treatment with vitamin E in systemic sclerosis: a double blind, randomized, controlled clinical trial of efficacy based on urinary isoprostane measurement

This double blind randomized controlled trial was designed to investigate whether short-term vitamin E treatment at doses of 500 and 1000 mg/day, compared to placebo, decreased urinary F(2)-isoprostanes and improved the microvascular perfusion after cold exposure in patients suffering from SSc. Thirty-three eligible patients were randomly assigned in a 1.3:1:1 ratio to receive placebo, vitamin E 500 mg, or vitamin E 1000 mg daily for 3 weeks. Clinical examination, analysis of plasma vitamin E, urinary F(2)-isoprostane levels and a whole body cooling test were performed at baseline and after a 3-week period of treatment. Urinary 15-F(2t)-IsoP levels and cutaneous blood flow variation in response to cold did not significantly differ before versus after treatment in any group. Furthermore, no difference was found between groups after 3 weeks of treatment. We show that 3-week vitamin E treatment at doses of 500 or 1000 mg/day neither decreases the basal rate of lipid peroxidation nor improves microvascular perfusion after cold exposure. These data does not support the need for phase III clinical trials to test efficacy of vitamin E in SSc.     

Oil rich in carotenoids instead of vitamins C and E as a better option to reduce doxorubicin-induced damage to normal cells of Ehrlich tumor-bearing mice: hematological,toxicological and histopathological evaluations

The development of therapeutic strategies to attenuate chemotherapy toxicity represents an area of great interest in cancer research, and among them is nutritional therapy based on antioxidants. As research on this topic is still controversial and scarce, we aim to investigate the effects of antioxidant supplementation with vitamin C, vitamin E or pequi oil, a carotenoid-rich oil extracted from pequi (Caryocar brasiliense), on doxorubicin (DX)-induced oxidative damage to normal cells in Ehrlich solid tumor-bearing mice. Tumor weight and volume, histopathology, morphometry and immunohistochemistry were used to assess the treatments' efficacy in containing tumor aggressiveness and regression, while possible toxicity of treatments was assessed by animals' weight, morphological analysis of the heart, liver and kidneys, hemogram, and serum levels of total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, creatinine and urea. Although all the chemotherapeutic treatments increased internal necrosis area and reduced the positive Ki-67 cells compared to non-treated tumors, the treatments with pequi oil provided before tumor inoculation (PTDX) or in continuous and concurrent administration with doxorubicin (PTPDX) were more effective in containing tumor growth, besides increasing lymphocyte-dependent immunity and reducing the adverse side effects associated with DX-induced oxidative damage to normal cells, mainly the PTDX treatment. Vitamins C and E given before tumor inoculation and chemotherapy were not successful against doxorubicin-induced cardiotoxicity, besides increasing doxorubicin-induced nephrotoxicity, indicating that, at least for doxorubicin, pequi oil instead of vitamins C and E would be the best option to reduce its adverse effects.