Nutritional-inflammation status and resistance to erythropoietin therapy in haemodialysis patients.

BACKGROUND: Chronic kidney disease patients who are resistant to erythropoietin (EPO) treatment may suffer from malnutrition and/or inflammation. METHODS: In a cross-sectional study of haemodialysis patients, we investigated the relationship between the natural logarithm of the weekly EPO dose normalized for post-dialysis body weight and outcome measures of nutrition and/or inflammation [BMI, albumin and C reactive protein (CRP)] by means of multiple linear regression analysis. On the basis of the decile distribution of weekly EPO doses, we also evaluated four groups of patients: untreated, hyper-responders, normo-responders and hypo-responders. RESULTS: Six hundred and seventy-seven adult haemodialysis patients were recruited from five Italian centres. BMI and albumin were lower in the hypo-responders than in the other groups (21.3+/-3.8 vs 24.4+/-4.7 kg/m(2), P<0.001; and 3.8+/-0.6 vs 4.1+/-0.4 g/dl, P<0.001), whereas the median CRP level was higher (1.9 vs 0.8 mg/dl, P = 0.004). The median weekly EPO dose ranged from 30 IU/kg/week in the hyper-responsive group to 263 IU/kg/week in the hypo-responsive group. Transferrin saturation linearly decreased from the hyper- to hypo-responsive group (37+/-15 to 25+/-10%, P = 0.003), without any differences in transferrin levels. Ferritin levels were lower in the hypo-responsive than in the other patients (median 318 vs 445 ng/ml, P = 0.01). At multiple linear regression analysis, haemoglobin, BMI, albumin, CRP and serum iron levels were independently associated with the natural logarithm of the weekly EPO dose (R(2) = 0.22). CONCLUSIONS: Our findings support a clear association between EPO responsiveness and nutritional and inflammation variables in haemodialysis patients; iron deficiency is still a major cause of hypo-responsiveness.     

Pharmacokinetics of the 13C labeled anticancer agent temozolomide detected in vivo by selective cross-polarization transfer

The anticancer agent temozolomide labeled with ¹³C (8-Carbamoyl-3-13C-methylimidazo-[5,1-d]-1,2,3,5-tetrazin-4-(3H)-one), was noninvasively detected in subcutaneous RIF-1 tumors by a selective cross polarization ¹³C NMR method, at a field strength of 9.4T. Pharmacokinetics of the drug, at a dose of 150 mg/kg, were determined for intravenous and intraperitoneal modes of administration (three animals per mode). The half-life of the drug in the tumors was approximately 60 min. The uptake and clearance of the drug, however, varied significantly between individual hosts, for both modes of administration. These results demonstrate the feasibility of obtaining pharmacokinetics of anticancer agents for individual tumors without the need for a label that might modify drug activity (e.g., fluorine). The variability of the in vivo measurements, even within the same tumor model, demonstrates the necessity of directly monitoring the tumor to evaluate drug pharmacokinetics.     

补肾中药对肾虚骨质疏松症大鼠红细胞膜PKC、 Ca2+-Mg2+- ATP酶活性影响的实验研究

本实验研究切除卵巢造成肾虚骨质疏松症大鼠模型。通过观测红细胞膜蛋白激酶Ｃ（ＰＫＣ）和Ｃａ２＋－Ｍｇ２＿－ＡＴＰ酶的活性，探讨肾虎骨质疏松症病理机制中肌醇脂质系统的变化，并结合全身和脊柱骨密度（ＢＭＤ）指标观察了补肾中药（密骨灵）的疗效，与正常对照组、模型空白组和阳性药（骨疏康颗粒剂）对照组进行对照，探讨补肾法的防治机理。结果表明；模型空白组大鼠红细胞膜ＰＫＣ和Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶、Ｍｇ２＋－ＡＴＰ酶的活性明显低于正常组（ｐ均＜０．０５）；密骨灵组与骨疏康组大鼠全身、脊柱ＢＭＤ和红细胞膜ＰＫＣ、Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶的活性均明显高于模型空白组（ｐ均＜０．０５），并且与正常组大鼠无明显差别（ｐ均＞０．０５）；密骨灵组大鼠红细胞膜Ｍｇ２＋－ＡＴＰ酶活性高于模型空白组和骨疏康组（ｐ＜０．０５），并且与正常组无显著性差异（ｐ＞０．０５）；密骨灵组大鼠红细胞膜ＰＫＣ活性高于骨疏康组（Ｐ＜０．０５）。结论：肾虎骨质疏松症具有红细胞膜ＰＫＣ和Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶、Ｍｇ２＋－ＡＴＰ酶活性的改变；密骨灵可以恢复肾虎骨质疏松症大鼠全身骨量，达到防治目的；补肾中药可以恢复红细胞膜ＰＫＣ活性和钙镁泵的活性，是补     

Effect of hepatitis C antibody screening in blood donors on post-transfusion hepatitis in Taiwan

A national screening programme for antibody to hepatitis C virus (HCV) in blood donors in Taiwan began in July 1992 using a second-generation immunoassay. To study the impact of this screening on post-transfusion hepatitis in Taiwan, a prospective study on post-transfusion hepatitis, that was started in 1987, was continued. As of June 1994, 245 patients who received a blood transfusion after July 1992 had completed a follow-up period for more than 6 months post-transfusion. Of them, seven (2.8%) recipients developed acute post-transfusion hepatitis. The hepatitis in six cases could not be attributed to infection by hepatitis A, B, C, D, E viruses or cytomegalovirus (CMV) or Epstein-Barr virus (EBV). The remaining patient seroconverted to both IgG and IgM anti-CMV. All seven patients recovered in 6 months without development of chronicity, and the mean peak alanine aminotransferase level was lower compared with that of the cases before anti-HCV screening (i.e. pre-July 1992). These results indicate that the current anti-HCV screening has effectively interrupted HCV transmission through blood transfusion in Taiwan.     

巨噬细胞杀伤白色念珠菌作用的探讨

本研究经杀菌试验和免疫后保护力试验探讨小鼠巨噬细胞在抗白色念珠菌感染中的作用,结果表明白色念珠菌酵母形体对巨噬细胞杀伤作用的抵抗力及对小鼠的毒力均较菌丝形体强。小鼠体内不同部位巨噬细胞杀伤白色念珠菌的作用不同,脾脏巨噬细胞作用大于腹腔残存巨噬细胞。经白色念珠菌活菌静脉免疫后脾巨噬细胞杀白色念珠菌作用增强,但其对再感染的抵抗力不增强。     

HCV的检测方法

从发现丙型肝炎病毒以来 ,丙肝的检测技术发展迅速 ,灵敏度和特异性都有明显的提高 ,方法学在不断改进完善。笔者就近年来丙型肝炎的实验室检测方法作简要的综述     

Papillitis and vasculitis of the arteria spinalis anterior as complications of hepatitis C reinfection after liver transplantation

It is well known that hepatitis C virus (HCV)-related chronic liver disease may be associated with various immunological disorders including mixed cryoglobulinemia, which is accompanied by cutaneous vasculitis, arthralgias, membranoproliferative glomerulonephritis, and neuropathy in association with cryoprecipitable immune complexes in serum. We describe here the first case of central nervous system HCV infection with evidence of the virus in the cerebrospinal fluid in association with cryoglobulinemia in a patient who developed recurrent episodes of papillitis and vasculitis of the arteria spinalis anterior after liver transplantation. Received: 3 September 1996 Received after revision: 13 November 1996 Accepted: 6 December 1996     

重组血管内皮细胞生长因子在大肠杆菌的高效表达

目的:使重组血管内皮细胞生长因子(VEGF)在大肠杆菌中得到高效表达.方法:通过构建表达重组VEGF的质粒PRL621/VEGF,并在大肠杆菌中高效表达.结果:表达量约占菌体总蛋白的40%.对形成包含体的表达产物进行变性,初步复性处理,得到重组人VEGF粗提液,鸡胚绒毛尿囊膜试验表明有促血管生长活性,N-端15个氨基酸序列分析结果,与天然VEGF蛋白质相应序列一致.     

Changes in Neutrophil Oxidative Potential in Patients Undergoing Cardiopulmonary Bypass with Polypropylene Hollow Fiber Oxygenators

Neutrophil oxidative metabolism, C3d and beta 2 microglobulin levels, were assessed in nine consecutive patients undergoing cardiopulmonary bypass surgery with polypropylene hollow fiber oxygenators for open cardiac operations. Generation of oxygen free radicals by neutrophils was measured as luminol-enhanced chemiluminescence after stimulation with opsonized Zymosan and phorbol myristate acetate. A significant increase in light emission was detected by using both of the chemiluminescence stimulators. Moreover, a remarkable and significant increase in C3d levels was found already at 10 min. Conversely minimal changes in levels of beta 2 microglobulin were detected during cardiopulmonary bypass surgery. These data suggest that the impact of the patient blood with the foreign surface of cardiopulmonary bypass results in activation of phagocyte cells with increased potential in oxygen consumption. These effects could be partially complement-mediated.     

Biochemical evidence for the involvement of central serotonergic neurotransmission in the action of the antidepressant drug Medifoxamine

Medifoxamine, an antidepressant agent which has an original chemical structure, has been shown through in vitro studies, utilising radioligand binding in tissue homogenates, to bind with moderately high affinity to 5-HT_1c and 5-HT₂ receptor subtypes and to 5-HT uptake sites (IC₅₀ 950, 980, and 1,500 nM, respectively). It has been shown to bind in vivo to rat brain 5-HT₂ receptors after acute treatment with high dose (50 mg/kg, i.e., 133.9 μmol/kg). After 14 days continuous treatment with low dose (20 mg/kg, 53.6 μmol/kg), a decrease in the capacity of [³H]-5-HT uptake and a dose-dependent down-regulation of 5-HT₂ receptors in rat cerebral cortex were observed. These results indicate that medifoxamine, which has been shown previously to act through dopaminergic systems, interacts also with central serotonergic neurotransmission and particularly with the 5-HT₂ receptors, which could contribute to its antidepressant effect.