茶多酚治疗慢性酒精性肝损伤的实验研究

目的 建立酒精性肝病大鼠模型,观察茶多酚对酒精性肝病大鼠血清氨基转移酶活性和肝脏病理变化的影响,探讨茶多酚对酒精性肝损伤的防治作用。 方法 SD大鼠分成3组:酒精组(酒精7g·kg-1·d-1灌胃)、茶多酚组(酒精7g·kg-1·d-1 茶多酚0.25g·kg-1·d-1灌胃)和对照组(等渗盐水灌胃)。各组分别于4周末、12周末和24周末处死大鼠留取肝脏标本,用于HE染色和Masson染色。 结果 酒精组大鼠血清氧基转移酶水平较对照组升高,茶多酚组大鼠与酒精组相比,其值有明显降低,差异有统计学意义(P<0.05)。HE染色显示酒精组大鼠肝细胞浆出现不同程度的脂肪变性,小叶各带可见不同程度的点、灶状或片状坏死,24周大鼠可见桥接坏死。Masson三色染色可见24周大鼠汇管区边缘有绿染胶原纤维包绕增生,肝窦中可见绿染胶原纤维分布。茶多酚组肝脂肪变和炎症程度轻于酒精组,未发现桥接坏死。 结论 茶多酚对酒精性肝损伤具有一定的保护作用。     

Development of a marrow transplant regimen for acute leukemia using targeted hematopoietic irradiation delivered by 131I-labeled anti-CD45 antibody, combined with cyclophosphamide and total body irradiation

In an attempt to decrease the relapse rate after bone marrow transplantation (BMT) for advanced acute leukemia, we initiated studies using 131I-labeled anti-CD45 antibody (BC8) to deliver radiation specifically to hematopoietic tissues, followed by a standard transplant preparative regimen. Biodistribution studies were performed in 23 patients using 0.5 mg/kg trace 131I-labeled BC8 antibody. The BC8 antibody was cleared rapidly from plasma with an initial disappearance half-time of 1.5 +/- 0.2 hours, presumably reflecting rapid antigen- specific binding. The mean radiation absorbed doses (cGy/mCi131I administered) were as follows: marrow, 7.1 +/- 0.8; spleen, 10.8 +/- 1.4; liver, 2.7 +/- 0.2; lungs, 2.1 +/- 0.1; kidneys, 0.7 +/- 0.1; and total body, 0.4 +/- 0.03. Patients with acute myelogenous leukemia (AML) in relapse had a higher marrow dose (11.4 cGy/mCi) than those in remission (5.2 cGy/mCi; P = .001) because of higher uptake and longer retention of radionuclide in marrow. Twenty patients were treated with a dose of 131I estimated to deliver 3.5 Gy (level 1) to 7 Gy (level 3) to liver, with marrow doses of 4 to 30 Gy and spleen doses of 7 to 60 Gy, followed by 120 mg/kg cyclophosphamide (CY) and 12 Gy total body irradiation (TBI). Nine of 13 patients with AML or refractory anemia with excess blasts (RAEB) and two of seven with acute lymphocytic leukemia (ALL) are alive disease-free at 8 to 41 months (median, 17 months) after BMT. Toxicity has not been measurably greater than that of CY/TBI alone, and the maximum tolerated dose has not been reached. This study demonstrates that with the use of 131I-BC8 substantially greater doses of radiation can be delivered to hematopoietic tissues as compared with liver, lung, or kidney, which may improve the efficacy of marrow transplantation.     

Quantification of the breakpoint cluster region rearrangement for clinical monitoring in Philadelphia chromosome-positive chronic myeloid leukemia

The purpose of this report was to evaluate scintigraphy analysis of Southern blot hybridization as a method to quantify the breakpoint cluster region (BCR) rearrangement of Philadelphia chromosome (Ph)+ chronic myelogenous leukemia (CML). Cytogenetic and molecular studies performed simultaneously on 474 bone marrow and/or blood samples from 300 patients treated with alpha-interferon-based therapy were compared. Molecular results were expressed as the percentage of rearranged BCR bands versus the total scintigraphic signal. The percentage of Ph+ metaphases was calculated on 25 metaphases. The results of molecular studies obtained on both peripheral blood and bone marrow samples were identical. The rank correlation between the BCR quantification and the percentage of Ph positivity in 465 samples was excellent (r = .78). However, of 99 samples with a normal karyotype, 24% had a BCR rearrangement. Of 86 samples with no BCR rearrangement, 13% showed a Ph chromosome. Of 49 samples with partial cytogenetic remission (Ph+ metaphases, 1% to 34%), 23% had no BCR rearrangement. In samples with a minor or no cytogenetic response (Ph+ metaphases, > 34%), BCR analysis overestimated the degree of response in 73 of 326 samples (22%). Nevertheless, survival analysis by BCR quantification level showed statistically better outcome for patients in complete or partial molecular response (P < .01). Molecular quantification of BCR was useful in monitoring the course of Ph+ CML. This method, which can be used on peripheral blood, detected residual disease not shown by cytogenetic analysis and was prognostically relevant as a measure of disease suppression.     

Ⅱ型胶原在T-2毒素诱导大鼠关节软骨早期损伤中的干预作用

目的 观察Ⅱ型胶原在T-2毒素诱导大鼠关节软骨早期损伤中的干预作用,在分子水平上寻找软骨损伤及修复的分子学生物标志,为探讨关节软骨损伤疾病的防治措施提供理论依据.方法 Wistar大鼠80只,按体质量随机分为4组:阴性对照组、阳性对照组、高剂量干预组、低剂量干预组,每组20只.阴性对照组食用常规成品颗粒饲料,其他3组食用含100 ng/kg T-2毒素染毒饲料;阴性对照组和阳性对照组饮自来水;低、高剂量干预组饮用含Ⅱ型胶原0.5、5.0 g/L的自来水.在3、5个月时处死大鼠,光镜下观察大鼠透明软骨的组织病理学改变,用酶联免疫吸附试验(ELISA法)检测大鼠血清Ⅱ型胶原羧基末端肽(CTX-Ⅱ)、软骨寡聚基质蛋白(COMP)及尿中吡啶啉(DPD)含量.结果 光镜下阳性对照组大鼠关节软骨细胞排列紊乱,软骨细胞变形、变性,可见大面积的软骨细胞坏死,而高、低剂量干预组表现为软骨表面原纤维形成,表层软骨细胞肿胀变圆,扁平的软骨细胞减少,软骨细胞簇集等骨关节炎早期病理改变.在3、5个月时,阴性对照组、阳性对照组、高剂量干预组、低剂量干预组大鼠血清CTX-Ⅱ含量分别为(18.77±4.61)、(25.07±9.17),(24.43±5.23)、(39.17±10.49),(21.11±5.02),(33.20±9.74),(19.87±4.53)、(29.73±9.32)μg/L;血清COMP含量分别为(5.43±2.75)、(6.38±2.23),(21.37±4.72)、(24.52±4.26),(17.27±4.77)、(20.32±4.74),(20.13±5.07)、(19.44±4.92)μg/L.其中,3个月时,与阴性对照组比较,阳性对照组血清CTX-Ⅱ含量明显升高(P＜0.05),而低、高剂量干预组未见明显改变(P均＞ 0.05);5个月时,与阴性对照组比较,其他3组血清CTX-Ⅱ含量明显升高(P均＜ 0.05),而高、低剂量干预组明显低于阳性对照组(P均＜0.05).3个月时,与阴性对照组比较,其他3组血清COMP含量明显升高(P均＜0.05),而与阳性对照组比较,高剂量干预组血清COMP含量明显降低(P＜0.05);5个月时,与阴性对照组比较,其他3组血清COMP含量明显升高(P均＜0.05),而与阳性对照组比较,高、低剂量干预组血清COMP含量明显降低(P均＜0.05).3、5个月时,上述4组大鼠尿液DPD含量分别为( 3.47±2.20)、(4.14±1.06),(4.09±2.48)、(4.33±3.43),(3.86±2.31)、(5.72±3.89),(3.58±2.77)、(4.23±2.90)μg/L,组间比较,差异无统计学意义(F值分别为2.608、2.436,P均＞0.05).结论 Ⅱ型胶原能拮抗T-2毒素的软骨损伤作用,延缓关节软骨的破坏进程,降低大鼠血清中CTX-Ⅱ及COMP水平.     

内皮脂酶与高密度脂蛋白代谢

内皮脂酶是近年来发现的甘油三酯脂肪酶基因家族新成员.该家族还包括脂蛋白脂肪酶、肝脂肪酶.内皮脂酶具有磷脂酶活性,可参与脂蛋白代谢,尤其对血浆中的高密度脂蛋白代谢及高密度脂蛋白胆固醇水平具有明显调节作用.近来研究证明,抑制内皮脂酶可提高人血浆高密度脂蛋白胆固醇水平.但目前内皮脂酶与高密度脂蛋白胆固醇、胆固醇逆行转运及动脉粥样硬化之间的关系仍尚无明确定论,且有待进一步研究.     

Search for intrafamilial transmission of hepatitis C virus in hemophilia patients

This study was performed to determine the risk of family members of anti-hepatitis C virus (HCV)-positive hemophilia patients (index patients) for infection with HCV compared with the risk of acquiring hepatitis B virus (HBV), human immunodeficiency virus (HIV), and hepatitis A virus (HAV) infection. All index patients (n = 141) were found to be positive by first and second generation anti-HCV enzyme immunoassays (EIAs). Among their household contacts (n = 228), 224 were negative and 1 positive by both assays. Three contacts gave positive results in first generation anti-HCV EIA and negative results in second generation assay. This latter result was confirmed by further tests (neutralization test, synthetic peptides, and supplemental assay). Percent positivity for anti-HBc was about the same in non-sexual household contacts and sexual partners (13 of 109 [12%] and 7 of 54 [13%], respectively). Percent prevalence of anti-HBc was higher in contacts of index patients with chronic hepatitis B than in those of index patients who had recovered from that disease (6 of 20 [30%] and 14 of 133 [10%], respectively; P < .05). The HBV infection rate of contacts participating in controlled self-treatment was not higher than that of controls (3 of 57 [5%] and 10 of 98 [10%], respectively). Of 44 sexual partners, 5 (11%) were found to be positive for anti-HIV. Prevalence of anti-HAV matched with the age-related distribution in the German population. These findings suggest that intrafamilial transmission of HCV to family members of hemophilia patients is uncommon. In contacts of hemophilia patients, the risk of acquiring HBV infection seems to be as high in household contacts as in sexual contacts. Participation in controlled self-treatment does not appear to be an additional risk for HCV and HBV infection. There is no doubt that sexual transmission of HCV is less common than that of HBV and HIV.     

Tumor necrosis factor-α and interleukin-6 in cirrhotic patients with spontaneous bacterial peritonitis

AIM: To evaluate the role of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis (SBP).METHODS: We prospectively studied 120 cirrhotic patients with SBP and 80 cirrhotic patients with sterile ascitic fluid. They included 144 males and 56 females with ages ranging between 34 and 62 years. The diagnosis of cirrhosis was established by clinical and laboratory criteria that did not require histological confirmation. The severity of underlying liver disease was evaluated using Pugh’s modification of Child’s criteria (Child-Pugh scores). Ascitic fluid was sent to the laboratory for cell count, culture, sensitivity testing, and measurement of chemical elements (i.e., albumin, glucose). Specimens were inoculated into aerobic and anaerobic blood culture bottles. Serum and ascitic fluid were also collected in sterile tubes at study entry (before the initiation of antibiotic treatment) and 48 h later. Assays for TNF-α and IL-6 in the serum and ascitic fluid were performed with an immunoenzymometric assay using manufacture’s instructions.RESULTS: Cytokine levels in serum and ascitic fluid were significantly higher in the patients with SBP. (plasma TNF-α: 135.35 ng/mL ± 11.21 ng/mL vs 92.86 ng/mL ± 17.56 ng/mL, P < 0.001; plasma IL-6: 32.30 pg/mL ± 7.07 pg/mL vs 12.11 pg/mL ± 6.53 pg/mL, P < 0.001; ascitic fluid TNF-α: 647.54 ± 107.11 ng/mL vs 238.43 ng/mL ± 65.42 ng/mL, P < 0.001); ascitic fluid IL-6: 132.84 ng/mL ± 34.13 vs 40.41 ± 12.85 pg/mL, P < 0.001). About 48 (40%) cirrhotic patients with SBP developed renal and hepatic impairment and showed significantly higher plasma and ascitic fluid cytokine levels at diagnosis of infection. [(plasma TNF-α: 176.58 ± 17.84 vs 135.35 ± 11.21 ng/mL) (P < 0.001) and (IL-6: 57.83 ± 7.85 vs 32.30 ± 7.07 pg/mL) (P < 0.001); ascitic fluid TNF-α: 958.39 ± 135.72 vs 647.54 ± 107.11 ng/mL, (P < 0.001), ascitic fluid IL-6: 654.74 ± 97.43 vs 132.84 ± 34.13 pg/mL, (P < 0.001)]. Twenty nine patients (60.4%) with SBP and renal impairment died whereas, only four patients (5.55%) with SBP but without renal impairment died from gastrointestinal hemorrhage (P < 0.0005).CONCLUSION: It appears that TNF-α production may enhance liver cell injury and lead to renal impairment. This correlated well with the poor prognosis and significantly increased mortality associated with SBP in cirrhotic patients.