The effect of diet on total antioxidant status,ceruloplasmin, transferrin and ferritin serum levels in phenylketonuric children

Objectives: To investigate the effect of diet on total antioxidative status (TAS), transferrin, ferritin and ceruloplasmin serum levels in phenylketonuric (PKU) children. Patients and methods: Seventeen poorly controlled PKU children underwent clinical and laboratory examinations before, ‘off diet’, and 60 days after adhering to their special diet ‘on diet’, whereas controls (N = 24) were examined once. Blood chemistry was performed with the appropriate methodologies. Results: Phenylalanine levels differed significantly among the examined groups. Lipids and lipoproteins were higher in ‘off diet’ than in ‘on diet’ group, except of high density lipoprotein and apolipoprotein AI that remained unaffected. Total antioxidative status (386 ± 30 vs 204 ± 23 μmol/L, p < 0.001), ferritin (48.2 ± 2.3 vs 33.0 ± 2.8 μg/L, p < 0.001) and ceruloplasmin (40.02 ± 2.5 vs 25.5 ± 2.8 mg/dL, p < 0.001) levels were significantly higher in ‘on diet’ patients’ group compared to ‘off diet’ one. The low lipoprotein and the high TAS and ferritin levels in patients with PKU ‘on diet’ may be related to the vegetarian diet and the rich in iron formula supplementation. Conclusions: The low ferritin levels found in ‘off diet’ patients with PKU may be attributed to a decreased liver production of ceruloplasmin, which evaluation may be a useful tool for the follow‐up of patients with PKU.     

Association study between iron-related genes polymorphisms and Parkinson's disease

We have conducted a case-control study in order to test for an association between 8 intragenic polymorphisms of 5 iron-related genes (transferrin, transferrin receptor1, HFE, frataxin and lactoferrin) and Parkinson disease. Comparison of genotypes and allele frequencies did not differ significantly between cases and controls for all studied polymorphisms except the G258S transferrin polymorphism, for which a higher frequency of the G allele was found among cases (p=0.033), particularly among cases with onset older than 60 (p=0.0017) and with negative family history (p=0.022). This finding suggests that genetic variations in the control of iron metabolism may contribute to the pathogenesis of the disease. Received: 23 July 2001, Received in revised form: 8 November 2001, Accepted: 14 November 2001     

血清可溶性转铁蛋白受体及转铁蛋白在儿童缺铁性贫血合并感染中的诊断价值

目的探讨血清可溶性转铁蛋白受体（sTfR）、转铁蛋白（Tf）在儿童缺铁性贫血合并急性感染（iron deficiency with acute infection，IDAI）中的变化和诊断价值。方法采用速率散射免疫比浊法，测定IDAI组、单纯缺铁性贫血（IDA）组、IDAI组治疗后及健康对照组的血清sTfR、Tf、铁蛋白（SF）水平。常规铁染色观察骨髓储存铁。结果IDAI组和IDA组患儿sTfR、Tf均显著高于对照组（P〈0．01），两组间无显著差异（P〉0．05），IDAI组治疗后血红蛋白（Hb）上升至100g／L以上，但与对照组还有差距时（P〈0．05），sTfR、Tf值降至对照组水平（P〉0．05）。结论sTfR、Tf对诊断缺铁性贫血特异强，测定结果不受感染因素干扰，是临床判断贫血合并感染儿童是否缺铁和监测疗效的可靠指标，临床应用价值优于SF和骨髓储存铁。     

Innovative technologies for the diagnosis of alcohol abuse and monitoring abstinence

This article summarizes the proceedings of a workshop presented at the 2000 RSA Meeting in Denver, Colorado. The aim of this workshop was to discuss the basic methodologies, diagnostic performance, and clinical utility of three technologies: carbohydrate-deficient transferrin, the "Early Detection of Alcohol Consumption" score, and whole blood associated acetaldehyde. Each method adopts a different strategy to identify heavy alcohol consumption and offers a unique approach to determine alcohol abstinence and relapses. Appropriate application of these technologies can lead to early intervention for alcohol problems before significant tissue damage occurs. To date these methodologies have yet to be formally contrasted and compared. Sensitivity, specificity, predictive value, availability, ease of use, and interpretation of tests results are important aspects to consider when selecting the most appropriate and cost-effective system. Critical evaluation of these methodologies can enable research and clinical laboratories to choose the system that best meets their particular needs in terms of assay feasibility, budget, and goals.     

CA125阴性卵巢癌血清标志物差异蛋白质组学的研究

目的:通过二维差异凝胶电泳(2-DEDIGE)和基质辅助激光解吸离子化-飞行时间(MALDI-TOF/TOF)串联质谱差异蛋白质组学方法寻找CA125阴性卵巢上皮癌血清标志物,以提高卵巢上皮癌诊断的灵敏度和特异度。方法:收集103例卵巢上皮癌,60例正常对照,63例卵巢良性肿瘤、63例盆腔良性病变的血清。按年龄匹配,选取6例CA125阴性卵巢癌和6例正常对照组的血清等容积混合。祛除血清高丰度白蛋白和IgG后进行2-DEDIGE。实验重复3次。通过DeCyder软件分析得出有显著差异的蛋白质点,MALDI-TOF/TOF鉴定差异蛋白质。分别用WesternBlot和ELISA方法验证获选的血清标志物。结果:(1)经2-DEDIGE实验得出有显著差异的蛋白质点41个,MALDI-TOF/TOF成功鉴定了其中的28个蛋白质点。上调最显著的蛋白质点为结合珠蛋白(haptoglo-bin,Hp),下调最显著的蛋白质为转铁蛋白(transferrin,Tf);(2)WesternBlot和ELISA验证结果显示,CA125阴性卵巢上皮癌血清Hp和Tf与正常对照有显著差异(P<0.001);(3)CA125+Hp+Tf联合检测(两者或两者以上阳性判断为阳性)诊断卵巢上皮癌的灵敏度和特异度高于CA125、Hp和Tf单独检测。结论:Hp和Tf是卵巢上皮癌血清中差异表达的蛋白质,可作为卵巢上皮癌的血清标志物。CA125+Hp+Tf联合检测有助于提高卵巢上皮癌诊断的灵敏度和特异度,有助于提高CA125阴性卵巢上皮癌的检出率。     

Oral iron is sufficient for erythropoietin treatment of very low birth-weight infants

The aim of this study was to compare two different doses and means of administration of iron in recombinant human erythropoietin (rHuEPO)-treated very low birth-weight (VLBW) infants. VLBW infants (n = 41) were randomized to one of three groups. Fourteen infants were treated with rHuEPO (300 IU/kg three times a week s.c.) and oral iron (ferrofumarate, 6 mg of iron/kg per day). Another 14 infants received the same erythropoietin dose and intramuscular iron (ferroxypolymaltose, once 12 mg of iron/kg weekly). Thirteen infants were treated with the same dose of intramuscular iron but did not receive rHuEPO. After the 3-week study period, haemoglobin concentrations and reticulocyte counts were similar in the rHuEPO-treated groups and both were higher than in the group not receiving rHuEPO (P < 0.001). In both rHuEPO-treated groups the transferrin receptor concentration increased from 6.8–7.2 mg/l to 10.5–11.3 mg/l. Conclusion In erythropoietin-treated very low birth weight infants the iron need for erythropoiesis can be met by oral administration of iron. Received: 17 November 1997 and in revised form: 6 March 1998 / Accepted: 30 April 1998     

Effects of Chronic Ethanol on Enzymes Regulating Sialylation and Desialylation of Transferrin in Rats

Transferrin is a N-glycosylated glycoprotein and plays an important role in iron transport from sites of absorption and storage to sites of utilization. Chronic ethanol alters the normal microheterogeneity pattern of transferrin as a consequence of changes in the sialic acid content. However the underlying basis of this change in sialic acid contents of transferrin in alcohol abuse remains unclear. We have undertaken this study in order to investigate the effects of chronic ethanol in rats with respect to the hepatic rate of (i) transferrin synthesis based on labeled leucine incorporation, (ii) the incorporation of labeled N-acetyl mannosamine (NAM) into sialic acid residues of transferrin, and (iii) roles of specific sialyltransferase and sialidase at hepatic subcellular level. The results showed no significant difference in the incorporation of labeled leucine into transferrin at all levels between the control and ethanol group, whereas the incorporation of NAM into transferrin was significantly decreased by 84% (p < 0.001) both at the whole cell and Golgi level. Thus, the incorporation of labeled NAM relative to the incorporation of labeled leucine into hepatic transferrin was significantly decreased by 86% (p < 0.001) in chronic ethanol-treated animals as compared with the controls both at the whole cell and Golgi levels. These data are further supported by our finding of concomitant decrease in the activity of β-galactoside α2,6-sialyltransferase by 58% (p < 0.01) in ethanol-treated rats as compared with control animals. In contrast, both the plasma membrane and plasma sialidase activities were increased by 95% (p < 0.01) and 85% (p < 0.01), respectively, in ethanol-fed rats as compared with their respective controls. We conclude that decreased activity of sialyltransferase and increased activity of sialidase sequentially at the plasma membrane and plasma compartment may be responsible for decreased incorporation of sialic acid residues in serum transferrin molecules after chronic ethanol treatment.     

Manganese oxidation state mediates toxicity in PC12 cells

The role of the manganese (Mn) oxidation state on cellular Mn uptake and toxicity is not well understood. Therefore, undifferentiated PC12 cells were exposed to 0-200 microM Mn(II)-chloride or Mn(III)-pyrophosphate for 24 h, after which cellular manganese levels were measured along with measures of cell viability, function, and cytotoxicity (trypan blue exclusion, medium lactate dehydrogenase (LDH), 8-isoprostanes, cellular ATP, dopamine, serotonin, H-ferritin, transferrin receptor (TfR), Mn-superoxide dismutase (MnSOD), and copper-zinc superoxide dismutase (CuZnSOD) protein levels). Exposures to Mn(III) >10 microM produced 2- to 5-fold higher cellular manganese levels than equimolar exposures to Mn(II). Cell viability and ATP levels both decreased at the highest Mn(II) and Mn(III) exposures (150-200 microM), while Mn(III) exposures produced increases in LDH activity at lower exposures (> or =50 microM) than did Mn(II) (200 microM only). Mn(II) reduced cellular dopamine levels more than Mn(III), especially at the highest exposures (50% reduced at 200 microM Mn(II)). In contrast, Mn(III) produced a >70% reduction in cellular serotonin at all exposures compared to Mn(II). Different cellular responses to Mn(II) exposures compared to Mn(III) were also observed for H-ferritin, TfR, and MnSOD protein levels. Notably, these differential effects of Mn(II) versus Mn(III) exposures on cellular toxicity could not simply be accounted for by the different cellular levels of manganese. These results suggest that the oxidation state of manganese exposures plays an important role in mediating manganese cytotoxicity.     

Retinol-binding protein, acute phase reactants and Helicobacter pylori infection in patients with gastric adenocarcinoma

AIM: To determine the serum levels of c-reactive protein (CRP), transferrin (TRF), a2-macroglobulin (A2M), ceruloplasmin (CER), a1-acid glycoprotein (AAG), pre-albumin (P-ALB) and retinol-binding protein (RBP) in gastric carcinoma patients and to explore their possible correlation with underlying Helicobacter pylori (H pylori) infection. METHODS: We measured the serum levels of CRP, TRF, A2M, CER, AAG, P-ALB, and RBP in 153 preoperative patients (93 males; mean age: 63.1±11.3 years) with non-cardia gastric adenocarcinoma and 19 healthy subjects. RESULTS: The levels of CRP, CER, RBP, and AAG in cancer patients were significantly higher than those in healthy controls (P<0.0001), while no difference was found regarding the TRF, P-ALB, and A2M levels. Cancer patients with H pylori infection had significantly lower RBP values compared to non-infected ones (P<0.0001) and also higher values of CRP and AAG (P=0.09 and P=0.08, respectively). CONCLUSION: High serum levels of CRP, CER and AAG in cancer patients do not seem to be related to H pylori infection. Retinol-binding protein seems to discriminate between infected and non-infected patients with gastric carcinoma. Further studies are needed to explore if it is directly involved in the pathogenesis of the disease or is merely an epiphenomenon.     

Gene frequencies of transferrin (TfC) subtypes in Western Germany (Düsseldorf region)

Summary Transferrin (Tf) subtypes were determined by isoelectric focusing and polyacrylamide gelelectrophoresis on samples from 380 unrelated individuals. The following gene frequencies were observed: Tf^C1 0.7816, Tf^C2 0.1355, Tf^C3 0.0711, and Tf^B 0.0118.Progress reports on this work were presented at the First International Anthropological Poster Conference, September 8–11, 1980, Zagreb, Yugoslavia