Enhanced cyclooxygenase 2-mediated vasorelaxation in coronary arteries from insulin-resistant obese Zucker rats

Objective

The expression of p53 has been associated with DNA damage, cell senescence, proliferation and apoptosis in human atherosclerotic plaques. However, it is largely unknown whether p53 expression is related to the stability and clinical manifestations of atherosclerotic plaques in humans. In the present study, we examined whether p53 expression is related to clinical symptoms and plaque integrity in patients with carotid atherosclerosis (n = 62). We also investigated p53 expression and its relation to apoptosis and apoptosis-related cathepsin L and ferritin in the carotid lesions.

Methods and results

We found that smooth muscle cells often had nuclear p53 in the shoulder region of carotid lesions while CD68-positive macrophages, which had both nuclear and cytoplasmic p53, frequently appeared in the surrounding areas of necrotic cores or plaque cap regions. Quantitative image analysis of immunohistochemistry showed that p53 expression was significantly increased in plaques with necrotic core formation or cap rupture and lesions from patients with transient ischemic attacks (TIAs). The levels of p53 expression was significantly increased in more severe stenosed lesions but decreased with prolonged time between symptom onset and carotid endarterectomy. Furthermore, p53 expression was significantly correlated with the expression of ferritin, lysosomal cathepsin L, and apoptosis.

Conclusion

The increased p53 expression, particularly macrophage p53 levels, is associated with the enlargement of necrotic cores, plaque rupture and clinical manifestations of carotid plaques. Concomitant increases of lysosomal cathepsin, ferritin, and p53 levels may promote the apoptosis and atheroma progression in patients with carotid atherosclerosis.     

Serum ferritin level as a marker of disease activity and renal involvement in Egyptian children with juvenile systemic lupus erythematosus

Introduction

Ferritin is an acute-phase reactant that is elevated in several autoimmune disorders. Serum ferritin levels have been correlated with disease activity scores of juvenile systemic lupus erythematosus (JSLE). Furthermore, enhanced levels of ferritin have also been described in lupus nephritis (LN).

透射比浊法铁蛋白试剂盒的性能评价

[目的]了解免疫透射比浊法铁蛋白试剂盒的性能指标。[方法]测定该试剂盒的不精密度、线性范围、灵敏度、准确度。[结果]免疫透射比浊法铁蛋白试剂盒的批内精密度1．0％～9．0％,批问精密度7．2％～11．8％,线性范围14～300斗∥L、灵敏度（检测低限）为14¨g／I．、准确度为105．9％。[结论]免疫透射比浊法检测铁蛋白在不精密度、线性范围、灵敏度、准确度方面均能满足临床需要,并且还具有快速、简便及成本低廉的特点,适合临床使用。     

血清铁蛋白检测对乙型肝炎的临床价值

对５４例乙肝患者，在作血清铁蛋白（ＳＦｅ）检测的同时进行肝活检与肝功检测。结果表明，ＳＦｅ升高与乙肝组织病理学改变总符合率为９４．５％，ＳＦｅ值增高者有肝病变，且增高程度与肝病变严重程度相一致；ＳＦｅ值正常者肝组织学结构基本正常。还发现，ＳＦｅ检测比ＡＬＴ更敏感，更能反映乙肝病变的实际情况。     

Concurrent repletion of iron and zinc reduces intestinal oxidative damage in iron- and zinc-deficient rats

AIM： To understand the interactions between iron and zinc during absorption in iron- and zinc-deficient rats, and their consequences on intestinal oxidant-antioxidant balance. METHODS： Twenty-four weanling Wistar-Kyoto rats fed an iron- and zinc-deficient diet （〈 6.5 mg Fe and 4.0 mg Zn/kg diet） for 4 wk were randomly divided into three groups （n = 8, each） and orally gavaged with 4 mg iron, 3.3 mg zinc, or 4 mg iron ＋ 3.3 mg zinc for 2 wk. At the last day of repletion, 3 h before the animals were sacrificed, they received either 37 mBq of SSFe or ^65Zn, to study their localization in the intestine, using microautoradiography. Hemoglobin, iron and zinc content in plasma and liver were measured as indicators of iron and zinc status. Duodenal sections were used for immunochemical staining of ferritin and metallothionein. Duodenal homogenates （mitochondrial and cytosolic fractions）, were used to assess aconitase activity, oxidative stress, functional integrity and the response of antioxidant enzymes. RESULTS： Concurrent repletion of iron- and zinc-deficient rats showed reduced localization of these minerals compared to rats that were teated with iron or zinc alone; these data provide evidence for antagonistic interactions. This resulted in reduced formation of lipid and protein oxidation products and better functional integrity of the intestinal mucosa. Further, combined repletion lowered iron-associated aconitase activity and ferritin expression, but significantly elevated metallothionein and glutathione levels in the intestinal mucosa. The mechanism of interactions during combined supplementation and its subsequent effects appeared to be due to through modulation of cytosolic aconitase, which in turn influenced the labile iron pool and metallothionein levels, and hence reduced intestinal oxidative damage.CONCLUSION： Concurrent administration of iron and zinc corrects iron and zinc deficiency, and also reduces the intestinal oxidative damage associated with iron supplementation.     

Effect of Chronic Alcohol Feeding on Hepatic Iron Status and Ferritin Uptake by Rat Hepatocytes

Alcohol abuse is known to cause disturbances to iron homeostasis in man and is associated with elevated serum ferritin levels. We have previously shown that ethanol metabolism in the rat hepatocyte is associated with an immediate reduction in ferritin uptake by this cell. In this study we have examined the effect of pair-feeding the Lieber-DeCarli liquid alcohol diet on ferritin uptake by rat hepatocytes. Rat liver ferritin was radiolabeled with ⁵⁹Fe in vivo and isolated by conventional techniques. Rats were pair-fed the Lieber-DeCarli liquid alcoholic diet for 4–6 weeks. Hepatocytes, isolated from their livers by collagenase perfusion, were incubated with [⁵⁹Fe]ferritin in L-15 medium at 37°C and 4° to measure ferritin uptake and binding. The in vitro effect of ethanol on these hepatocytes was also studied. Ferritin and iron parameters were measured in the sera and hepatocytes of these animals and a comparable group of normal chowfed rats. The rate of ferritin uptake by hepatocytes from alcohol-fed rats was significantly faster than that of their pair-fed controls (0.743 ± 0.061 vs. 0.540 ± 0.042 ng/min/10⁶ cells, p < 0.05). However, the rats on Lieber-DeCarli control diet exhibited a lower hepatocyte ferritin uptake rate than chow-fed animals (79.3 ± 8.1% of the control values, p < 0.01). In vitro incubation of cells in 100 mm ethanol resulted in less inhibition of ferritin uptake by hepatocytes from alcoholic rats than from their pair-fed controls (11 ± 7.1% inhibition vs. 43.6 ± 10.7% for controls, p < 0.05). Receptor-mediated binding of ferritin to hepatocytes showed a 61% increase in saturable binding capacity for alcoholic rats (15,820 ± 4950 molecules/cell vs. 9798 ± 3622, p= 0.05). The presence of ethanol in the medium did not affect ferritin binding significantly. Although there was no significant difference in the serum iron values between all three groups, transferrin concentrations were markedly elevated in the alcohol-fed rats, resulting in a much lower transferrin iron saturation than for the control animals. Because the corresponding serum values for the diet controls were intermediate between those for the alcohol-fed rats and the chow-fed animals, these findings may reflect dietary restriction by the liquid diet, which is exacerbated by the addition of alcohol. These findings suggest that there is increased iron uptake by the hepatocyte following chronic alcohol administration, which may be due to the increased ferritin receptors. This is supported by the observation that this alcohol treatment also causes a depletion of serum ferritin. However, the decreased iron content in the alcohol-fed rats indicate that this may be due to a response to changes in iron homeostasis by the hepatocyte and/or redistribution in the body.     

Identification and functional analysis of ferritin 2 from the Taiga tick Ixodes persulcatus Schulze

Ferritin 2 (FER2) is an iron storage protein, which has been shown to be critical for iron homeostasis during blood feeding and reproduction in ticks and is therefore suitable as a component for anti-tick vaccines. In this study, we identified the FER2 of Ixodes persulcatus, a major vector for zoonotic diseases such as Lyme borreliosis and tick-borne relapsing fever in Japan, and investigated its functions. Ixodes persulcatus-derived ferritin 2 (Ip-FER2) showed concentration-dependent iron-binding ability and high amino acid conservation, consistent with FER2s of other tick species. Vaccines containing the recombinant Ip-FER2 elicited a significant reduction of the engorgement weight of adult I. persulcatus. Interestingly, the reduction of engorgement weight was also observed in Ixodes ovatus, a sympatric species of I. persulcatus. In silico analyses of FER2 sequences of I. persulcatus and other ticks showed a greater similarity with I. scapularis and I. ricinus and lesser similarity with Hyalomma anatolicum, Haemaphysalis longicornis, Rhipicephalus microplus, and R. appendiculatus. Moreover, it was observed that the tick FER2 sequences possess conserved regions within the primary structures, and in silico epitope mapping analysis revealed that antigenic regions were also conserved, particularly among Ixodes spp ticks. In conclusion, the data support further protective tick vaccination applications using the Ip-FER2 antigens identified herein.     

中枢神经系统白血病脑脊液中白细胞介素2受体、铁蛋白和纤维结合蛋白的变化及其临床意义

目的探讨中枢神经系统白血病脑脊液中可溶性白细胞介素2受体、铁蛋白和纤维结合蛋白的变化及其临床意义。方法采用酶联免疫吸附法检测中枢神经系统白血病组(CNSL组),无中枢神经系统白血病组(无CNSL组)脑脊液中可溶性白细胞介素2受体、铁蛋白和纤维结合蛋白的变化。结果 CNSL组脑脊液中可溶性白细胞介素2受体、铁蛋白和纤维结合蛋白均高于无CNSL组和对照组,有显著性差异(p<0.05)。结论脑脊液中可溶性白细胞介素2受体、铁蛋白和纤维结合蛋白在中枢神经系统白血病的诊断中有重要意义,提示其联合检测对早期诊断中枢神经系统白血病有意义。