Selenium supplementation, soluble tumor necrosis factor-alpha receptor type 1, and C-reactive protein during psoriasis therapy with narrowband ultraviolet B

OBJECTIVE: We examined the influence of supplementation with selenomethionine on soluble tumor necrosis factor-alpha receptor type 1 (sTNF-R1) and C-reactive protein (CRP) concentrations in patients with psoriasis who were treated with narrowband ultraviolet B. METHODS: Thirty-seven patients had narrowband ultraviolet B therapy five times a week and received 200 mug of selenium daily as selenomethionine (group 1, n = 19) or placebo (group 2, n = 18) for 4 wk. Assessment, performed at baseline, after 2 and 4 wk, and 4 wk after the end of treatment included measurement of the Psoriasis Area and Severity Index (PASI) and serum concentrations of selenium (micrograms per liter), sTNF-R1 (nanograms per milliliter), and CRP (milligrams per liter). Control sera were obtained from 20 healthy volunteers. RESULTS: Baseline PASI was 12.70 +/- 5.48 (13.02 +/- 6.25 in group 1 and 12.37 +/- 4.71 in group 2), selenium concentration was 50.55 +/- 9.54 (49.05 +/- 10.38 and 52.13 +/- 8.61, respectively), sTNF-R1 concentration was 1.91 +/- 0.38 (1.96 +/- 0.37 and 1.87 +/- 0.40, respectively), and CRP concentration was 25.34 +/- 8.27 (26.12 +/- 8.42 and 24.57 +/- 7.72). In controls, selenium concentration was 48.71 +/- 9.39 (P > 0.05 versus patients), sTNF-R1 concentration was 1.48 +/- 0.30 (P < 0.05), CRP concentration was <6. The baseline sTNF-R1 level correlated to PASI value (r = 0.40, P < 0.05) and CRP concentration (r = 0.36, P > 0.05). The treatment resulted in an almost parallel decrease in PASI in both groups. At 4 wk after the end of treatment, selenium concentrations were 83.77 +/- 5.13 in group 1 and 52.12 +/- 7.54 in group 2 (P < 0.05), sTNF-R1 concentrations were 1.72 +/- 0.27 and 1.47 +/- 0.26 (P < 0.05), and CRP concentrations were 7.72 +/- 4.23 and 8.15 +/- 3.32, respectively (P > 0.05). Selenium concentration correlated inversely with CRP in group 1. CONCLUSION: The results confirm that sTNF-R1 and CRP concentrations are increated in active psoriasis and that supplementation with selenomethionine for 4 wk in safe doses is ineffacious as adjuvant therapy in patients with psoriasis.     

皖籍汉族人寻常型银屑病患者TNF-α基因多态性分析

目的　探讨TNF α基因多态性与皖籍汉族人寻常型银屑病的相关性。方法　采用PCR RFLP方法 ,检测皖籍汉族人 6 5例早发型 (Ⅰ型 )银屑病、2 2例迟发型 (Ⅱ型 )银屑病及 1 2 8例健康人TNFα- 2 38多态性。结果　早发型银屑病患者携带TNFα - 2 38.2 (TNF G/A基因型 )频率较对照组明显增高 (2 6 .2 %vs 1 0 .9% ) ,二者差异有显著性 (OR =2 .88,Pc<0 .0 5 ) ;而迟发型银屑病患者携带该基因型频率则与对照组差异无显著性 (9.1 %vs 1 0 .9% ,OR =0 .81 ,Pc>0 .0 5 )。但早发型银屑病男女患者携带TNFα- 2 38.2频率与相应对照组差异均无显著性 (Pc>0 .0 5 )。结论　TNFα- 2 38.2频率与皖籍汉族人寻常型银屑病发病类型明显关联 ,提示TNF α基因多态性可能为汉族人银屑病易感因子之一。     

肿瘤坏死因子在病毒性肝炎中的临床研究

近年来,细胞因子在病毒性肝炎发病机制中的作用越来越受到人们的重视.笔者对213例各型病毒性肝炎患者进行了血清肿瘤坏死因子(TNF-α)水平检验,以探讨其在病毒性肝炎中的作用.     

肿瘤坏死因子-a及其Ⅱ型受体基因多态性与矽肺

目的探讨肿瘤坏死因子-a(TNF-a)及其Ⅱ型受体(TNFRⅡ)基因多态性在矽肺发病遗传易感性中的作用及其与二氧化硅暴露的交互作用.方法选择259例矽肺患者和341例矽尘接触者(对照)为研究对象,对其职业史、尘肺病史、既往病史等进行问卷调查;拍摄其高仟伏X射线后前位胸片,根据尘肺病诊断标准进行诊断和分期;采集每个研究对象的外周静脉血,应用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)技术检测其TNF-a及TNFRⅡ基因多态性.结果在成组或11配对分析中,矽肺患者和矽尘接触者两组间TNF-a基因-308位点G/A+A/A基因型和TNFRⅡ196位点T/G+G/G基因型分布频率的差异均无统计学意义(P＞0.05).当接尘工龄＜15年时,G/A+A/A基因型携带者发生矽肺的危险性是G/G基因型的6.74倍,95%CI1.01～44.99.结论TNF-α和TNFRⅡ基因多态性在汉族人群矽肺发病的遗传易感性中不起主要作用.TNF-α基因-308位点基因多态性在矽肺发病过程中与接尘工龄存在交互作用,当累积接尘量较低时,G/A+A/A基因型携带者发生矽肺的危险性较G/G基因型明显增加.     

Practicalities of selenium supplementation in critically ill patients

PURPOSE OF REVIEW: To review the reason for and clinical effects of selenium supplementation in critically ill patients. RECENT FINDINGS: Selenium-dependent enzymes and selenoprotein P regulate immune and endothelial cell function. Obviously not the anorganic compounds of selenium but the activity of selenium-dependent enzymes is the most important factor modulating the immune system and the clinical outcome of patients. Despite low selenium levels in severely ill patients and low glutathione peroxidase activity associated with the extent of multiorgan dysfunction, only a few trials have investigated the effect of selenium supplementation on clinical outcome. A metaanalysis did not reveal a statistically significant survival rate with selenium supplementation, but suggested a dose-dependent trend. The recently completed multicentre trial on high-dose selenium supplementation in septic patients also did not reveal a significant overall reduction in mortality. SUMMARY: The available evidence suggests that selenoproteins play an important role in the immunomodulation of critically ill patients and a sodium selenite supplementation upregulates these selenoenzymes. The intervention trials with sodium selenite performed to date are small and therefore only a tendency in reduction of morbidity and mortality could be demonstrated. Larger trials are necessary to show the supposed benefits and risks of selenite supplementation in critically ill patients.     

Induction of tumor necrosis factor-alpha by cefodizime in U-937 cells

Cefodizime has modulating effects on the release of diverse cytokines. We determined the modulator activity of this antibiotic on the production of TNF in human monocytic U-937 cells. The measurement of TNF was carried out by ELISA test and by a L-929 cells-based citotoxic bioassay. The results showed that cefodizime alone induced the production of TNF on U-937 cells, however, the addition of LPS led to a decrease in the release of this cytokine (p < 0.05). On the other hand, the combination of cefodizime-PMA had a synergic effect (p < 0.05), while addition of LPS to this combination caused a decrease of TNF production (p < 0.05). With these results we conclude that cefodizime modulates the production of TNF in U-937 cells, which is down regulated by the addition of LPS.     

重型肝炎肝性脑病患者血氨和肿瘤坏死因子-α的相关性研究

目的 研究重型肝炎肝性脑病患者血氨和TNF-α的相关性.方法 采用ELISA法检测60例重型肝炎患者血清TNF-α含量,用酶法测定静脉血氨值.结果 在肝性脑病0级(15例)患者中血氨和TNF-α分别是(39.1±6.5)μmol/L和(72.34±7.25)ng/L,Ⅰ级(10例)分别是(55.3±9.2)μmol/L和(91.25±10.16)ng/L,Ⅱ级(16例)分别是(82.5±12.5)μmol/L和(128.25±13.45)ng/L,Ⅲ级(13例)分别是(124.6±21.3)μmol/L和(155.38±19.76)ng/L,Ⅳ级(6例)分别是(198.3±36.7)μmol/L和(186.39±23.54)ng/L.血氨和TNF-α之间具有显著的相关性(r=0.68.P＜0.01),并且血氨和TNF-α与肝性脑病的严重程度具有明显的相关性(r=0.91,P＜0.01和r=0.85.P＜0.01).结论 重型肝炎肝性脑病患者血氨和TNF-α具有显著的相关性,TNF-α可能参与肝性脑病的发病机制.     

Clinical and biochemical effects of coenzyme Q10, vitamin E,and selenium supplementation to psoriasis patients

ObjectiveThe aim of the present study was to evaluate clinical effects of supplementation with antioxidants to patients with severe erythrodermic (EP) and arthropathic (PsA) forms of psoriasis.MethodsFifty-eight patients were hospitalized, treated by conventional protocols, and randomly assigned to four groups. Groups EP1 and PsA1 were supplemented with coenzyme Q₁₀ (ubiquinone acetate, 50 mg/d), vitamin E (natural α-tocopherol, 50 mg/d), and selenium (aspartate salt, 48 μg/d) dissolved in soy lecithin for 30–35 d. Groups EP2 and PsA2 (placebo) received soy lecithin. Clinical conditions were assessed by severity parameters. Markers of oxidative stress included superoxide production, copper/zinc-superoxide dismutase, and catalase activities in the circulating granulocytes, in the affected epidermis, and plasma levels of nitrites/nitrates.ResultsAt baseline patients had an increased superoxide release from granulocytes (10.0 ± 0.5, 2.9 ± 0.2, and 1.5 ± 0.1 nmol/L per 10⁶ cells/h for EP, PsA, and donors, respectively), increased copper/zinc-superoxide dismutase and catalase activities in granulocytes in EP patients and decreased in PsA patients, decreased activity of copper/zinc-superoxide dismutase (0.3 ± 0.0, 1.8 ± 0.1, and 2.2 ± 0.2 U/mg protein for EP, PsA, and donors, respectively), and altered activity of catalase in psoriatic epidermis. Plasma levels of nitrites/nitrates were greater than normal in psoriatic patients. Supplementation resulted in significant improvement of clinical conditions, which corresponded to the faster versus placebo normalization of the oxidative stress markers.ConclusionSupplementation with antioxidants coenzyme Q₁₀, vitamin E, and selenium could be feasible for the management of patients with severe forms of psoriasis.     

肿瘤坏死因子-α基因多态性与早产

肿瘤坏死因子-α是一种具有多种生物学活性的多功能细胞因子,其编码基因具有多态性,这些多态性可以从转录水平上影响肿瘤坏死因子-α的表达,并与个体对疾病的易感性、发展、预后相关。研究表明早产患者羊水、血清、组织中肿瘤坏死因子-α表达量显著升高。该文就肿瘤坏死因子-α基因多态性与早产的相关性作以综述。     

Analysis of tumor necrosis factor-alpha, transforming growth factor-beta 1, interleukin-10, and interferon-gamma polymorphisms in patients with alcoholic chronic pancreatitis.

The pathophysiologic mechanisms underlying alcoholic chronic pancreatitis are poorly understood. Cytokines participate in the immunologic progression of acute and chronic pancreatitis and may play an important role in the development of pancreatic fibrosis. Functional polymorphisms in cytokine genes have been identified that alter cytokine production. The aims of the current investigation were to determine whether functional polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) gene at positions -308 and -238; in the transforming growth factor-beta 1 (TGF-beta(1)) gene at positions -509, +869 (codon 10), and +915 (codon 25); in the interleukin-10 (IL-10) gene at position -1082; and in the intron 1 of the interferon-gamma (IFN-gamma) gene at position +874 are associated with alcoholic chronic pancreatitis. We investigated 42 patients with alcoholic chronic pancreatitis. We studied 94 control subjects for the TNF-alpha polymorphisms and 73 control subjects for the remaining polymorphisms. Mutation analysis was performed by direct DNA sequencing or by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The genotype frequencies were similar between patients and control subjects for all investigated cytokine polymorphisms (P>.05). We did not find an association between the different genotypes and the clinical course of the disease. Therefore, we assume that these genetic variants do not play a dominant role in alcoholic chronic pancreatitis.     

Ethanol increases tumor necrosis factor-alpha receptor-1 (TNF-R1) levels in hepatic, intestinal, and cardiac cells.

Chronic ethanol consumption leads to cell injury in virtually every tissue. Tumor necrosis factor-alpha (TNF-alpha) constitutes a major factor in the development of alcohol-induced liver injury. In alcohol-dependent subjects, elevated levels of plasma TNF-alpha are strongly predictive of mortality. Binding of TNF-alpha to TNF-alpha receptor-1 (TNF-R1) activates death domain pathways, leading to necrosis and apoptosis in most tissues, and it also increases the expression of intercellular adhesion molecules (i.e., ICAM-1), which promote inflammation. We determined whether ethanol exposure leads to increases in cellular TNF-R1. We incubated HepG2 human hepatoma cells and H4-II-E-C3 rat hepatoma cells with 25, 50, and 100 mM ethanol for various intervals of time up to 48 h. Human colonic adenocarcinoma cells (Caco-2 cells) and neonatal rat primary cardiomyocytes were also incubated with different concentrations of ethanol. Levels of TNF-R1 were measured either by a sandwich enzyme-linked immunosorbent assay (ELISA) method or by determining the extracellular transmembrane domain of TNF-R1 by an intact-cell ELISA method. Ethanol exposure for 48 h increased TNF-R1 levels in human hepatoma cells in a dose-dependent manner. Levels increased significantly by 164% at 50 mM and by 240% at 100 mM ethanol. Effects were time dependent and did not reach a plateau at 48 h. Similar increases in TNF-R1 were also observed in rat hepatoma cells (90% at 50 mM and 230% at 100 mM ethanol). Under similar conditions, Caco-2 cells showed a significant 80% increase in TNF-R1 levels at 200 mM ethanol, a concentration found in intestine. Neonatal rat primary cardiomyocytes showed TNF-R1 increases of 36% at 50 mM and 44% at 100 mM ethanol. These results indicate that exposure of different cell types to pharmacologic concentrations of ethanol increases TNF-R1 levels and may augment TNF-alpha-mediated cell injury in different tissues.     

支气管哮喘患儿血清肿瘤坏死因子α及其可溶性受体1和2的检测及临床意义

【目的】 观察肿瘤坏死因子-α(TNF-α)及其可能性受体(sTNF-R1和sTNF-R2)在支气管哮喘患者中的表达,探讨它们在支气管哮喘炎症机制中的作用。 【方法】 采用ELISA法检测哮喘急性发作期和哮喘缓解期患儿及健康对照组儿童血清TNF-α、sTNF-R1和sTNF-R2的蛋白浓度。 【结果】 哮喘急性发作期组血清TNF-α、sTNF-R1 和sTNF-R2的蛋白浓度[分别为(3.19±1.68)、(4.69±2.30)、(14.32±6.19)] ng/mL显著高于对照组[(1.96±0.86)、(2.07±0.86)、(4.75±1.68)] ng/mL (P均＜0.01);哮喘缓解期组sTNF-R1 和sTNF-R2的蛋白浓度[分别为(2.59±1.21)、(11.57±4.78)] ng/mL显著低于哮喘急性发作期组(分别为P＜0.01和＜0.05),而TNF-α的蛋白浓度(2.75±1.31) ng/mL与哮喘急性发作期组相比差异无统计学意义(P>0.05);哮喘缓解期组TNF-α和sTNF-R2的蛋白浓度显著高于对照组(P均＜0.01),而sTNF-R1的蛋白浓度与对照组相比差异无统计学意义。sTNF-R1与sTNF-R2的表达水平呈显著正相关(n=99,r =0.239,P＜0.05),但sTNF-R1和sTNF-R2的表达水平分别与TNF-α之间无显著相关性(P>0.05)。 【结论】 TNF-α、sTNFR1和sTNFR2可能参与了哮喘的炎症发病过程,哮喘患者血清TNF-α、sTNF-R1和sTNF-R2水平增高可能被作为病情活动的指标之一。     

类风湿关节炎血清白细胞介素17和肿瘤坏死因子α及滑膜病变检测的意义

目的 探讨血清白细胞介素17(IL-17)和肿瘤坏死因子α(TNF-α)及滑膜病变检测在类风湿关节炎(RA)患者中的临床意义.方法 应用酶联免疫吸附测定法(ELISA)对50例活动期RA患者(活动期RA组)、50例稳定期RA患者(稳定期RA组)和50例体检健康者(健康对照组)血清IL-17和TNF-α水平进行检测,同时取其关节滑膜进行病理检查.结果 活动期RA组血清IL-17和TNF-α水平[(42.60±11.30)、(113.20±13.11) mg/L]明显高于稳定期RA组[(19.60±5.75)、( 14.50±5.33) mg/L]和健康对照组[(7.40±3.32)、( 10.90±2.24) mg/L](P＜ 0.01);稳定期RA组血清IL-17水平高于健康对照组(P＜0.05),而TNF-α水平与健康对照组比较差异无统计学意义(P＞0.05).RA患者的滑膜与健康对照组相比呈明显的病态.结论 RA患者血清IL-17和TNF-α水平及滑膜病变的变化特点与病情有关,联合动态监测有助于临床观察和治疗.     

急性失血患者血浆白细胞介素-6、白细胞介素-8、肿瘤坏死因子-α和一氧化氮合酶的变化探讨

目的 探讨急性失血患者血浆白细胞介素(IL)-6、IL-8、肿瘤坏死因子(TNF)-α和一氧化氮合酶(NOS)变化及其意义.方法 入选25例急性失血患者(失血组)和25例健康体检者(对照组),采用酶联免疫吸附法检测两组血浆IL-6、IL-8、TNF-α和NOS水平.结果 失血组血浆IL-6、IL-8、TNF-α和NOS水平明显高于对照组(0.284±0.027比0.204±0.016、0.059±0.079比0.037±0.039、0.460±0.024比0.372±0.018、0.637±0.054比0.443±0.040,P＜ 0.05或＜0.01).结论 急性锐器刺割伤致失血易引起血浆IL-6、IL-8、TNF-α和NOS水平升高,IL-6、IL-8、TNF-α释放加重组织器官损伤及失血性休克发展.NOS水平升高促进一氧化氮的合成增加,在急性失血血容量不足时促进微循环灌注,缓解组织灌注不足,可能对机体起保护作用.     

跨膜型肿瘤坏死因子-α对宫颈癌细胞毒性效应的研究

目的 观察跨膜型肿瘤坏死因子-α （TM-TNF-α）对人宫颈癌HeLa细胞的效应,并探讨其与人宫颈癌HeLa细胞死亡结构域沉寂子（SODD）表达的关系.方法 应用免疫细胞化学法检测增殖细胞核抗原（PCNA）表达;应用反转录-聚合酶链反应技术检测未经处理的和经TM-TNF-α作用后的人宫颈癌HeLa细胞SODD的表达情况及TM-TNF-α对其影响.结果 未经处理的人宫颈癌HeLa细胞PCNA阳性率为80.3％（155/193）,经TM-TNF-α作用后的人宫颈癌HeLa细胞PCNA阻性率降为46.7％（85/182）,两者比较差异有统计学意义（P＜0.05）.人宫颈癌HeLa细胞的聚合酶链反应循环次数设定为28次,所获扩增产物经2％琼脂糖凝胶电泳,经TM-TNF-α作用后的人宫颈癌HeLa细胞和未经处理的人宫颈癌HeLa细胞灰度值分别为1.377±0.170和0.815±0.040,两者比较差异有统计学意义（P＜0.05）.结论 TM-TNF-α可通过上调SODD的表达来增强其对人宫颈癌HeLa细胞的体外杀伤效应.     

The effect of selenium supplementation on selenium status of patients receiving chronic total parenteral nutrition

Patients receiving long-term total parenteral nutrition (TPN) are at risk for selenium deficiency. The purpose of this study was to determine the effect of parenteral selenium as selenious acid on the selenium status of seven long-term TPN patients. Patients received a dosage of zero, 80, or 160 micrograms Se/day for 1 month each. The measures of selenium status used were selenium levels in plasma and glutathione-peroxidase activities in erythrocytes and platelets. Urinary selenium excretion was measured. Control subjects were selected to match the sex, age, and weight of the patients. With increasing levels of parenteral selenium, there was increasing plasma selenium concentration as well as erythrocyte and platelet glutathione-peroxidase activity. There was no statistical difference between the patients during the time they received the 160 micrograms parenteral selenium treatment and the control subjects for platelet glutathione-peroxidase activity. At the 160 micrograms Se/day level, patient plasma selenium concentrations increased from 28% to 58% of the control levels. Four patients were studied after they returned to the 80 micrograms parenteral selenium/day from the 160-micrograms Se/day treatment. With decreasing parenteral selenium, three patients had decreasing platelet glutathione-peroxidase activity, while plasma selenium concentration decreased in two patients. These data suggest that some patients receiving long-term parenteral nutrition should receive parenteral selenium.     

亚临床甲状腺功能减退症患者血清C反应蛋白、肿瘤坏死因子-α及动脉粥样硬化关系的研究

目的 探讨亚临床甲状腺功能减退症(亚临床甲减)患者血清C反应蛋白(CRP)、肿瘤坏死因子β (TNF-α)及动脉粥样硬化的关系.方法 75例亚临床甲减患者根据促甲状腺激素(TSH)水平分为两组:轻度亚临床甲减(TSH 5.5～10.0 mU/L)组42例,重度亚临床甲减(TSH＞ 10.0mU/L)组33例;另选取健康体检者或志愿者30例作为对照组.所有受检者均检测三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、TSH、游离甲状腺素(FT4)、游离三碘甲腺原氨酸(FT3)、CRP 以及TNF-β,并测量颈动脉内膜-中层厚度(CIMT).结果 轻度亚临床甲减组、重度亚临床甲减组、对照组CIMT分别为(0.88±0.20)、(1.12±0.21)、(0.62±0.21)mm,轻度亚临床甲减组、重度亚临床甲减组CIMT均高于对照组,重度亚临床甲减组CIMT高于轻度亚临床甲减组,差异均有统计学意义(P＜0.01).三组 CRP、TNF-α比较差异无统计学意义(P＞0.05).轻度亚临床甲减组、重度亚临床甲减组 LDL-CC[( 3.22±0.37)、(3.49±0.38)mmol/L]均高于对照组[(2.48±0.41 )mmol/L],差异有统计学意义(P＜0.01);对照组、轻度亚临床甲减组 HDL-C、TG比较差异无统计学意义(P＞0.05);与对照组、轻度亚临床甲减组比较,重度亚临床甲减组HDL-C降低[(0.92±0.10)mmol/L比(1.21±0.14)、( 1.17±0.11) mmol/L],TG 增高[(1.50±0.49) mmol/L比(1.11±0.53)、(1.27±0.47) mmol/L],差异有统计学意义(P＜0.01或＜0.05).TG、LDL-C、TSH、CRP、TNF-α与CIMT 呈正相关(r=0.52、0.37、0.48、0.39、0.45,P＜0.05或＜0.01);FT4与CIMT 呈负相关(r=-0.24,P＜0.05);HDL-C与CIMT无相关性(r=0.06,P＞0.05).结论 亚临床甲减患者存在血脂代谢紊乱等多种异常,其发生动脉粥样硬化危险性增高,但炎性反应可能不是亚临床甲减并发动脉粥样硬化的主要因素.