Effects of hemodialysis, dialyser type and iron infusion on oxidative stress in uremic patients

Uremic patients undergoing hemodialysis (HD) are considered to face an elevated risk for atherosclerosis and cancer. This has been attributed in part to an increased oxidative stress. In this pilot study, oxidative cell damage in blood of HD-patients was compared to those of controls: total DNA damage (basic and specific oxidative DNA damage), modulation of glutathione levels (total and oxidized glutathione) and of lipid peroxidation were monitored via the Comet assay (with and without FPG), a kinetic photometric assay and HPLC quantification of plasma malondialdehyde (MDA), respectively. In some samples, leukocytes were analysed for malondialdehyde-deoxyguanosine-adducts (M1dG) with an immunoslot blot technique. HD-patients (n=21) showed a significant increase of total DNA damage (p<10(-12)), compared to controls (n=12). In a subset of patients and controls, GSSG levels and M1dG, however, only increased slightly, while tGSH and MDA levels did not differ. The influence of different low flux HD-membranes was tested in a pilot study with nine patients consecutively dialysed on three membrane types for four weeks each. In addition to the individual disposition of the patient, the dialyser membrane had a significant impact on oxidative stress. Total DNA damage was found to be almost identical for polysulfone and vitamin E coated cellulosic membranes, whereas a slight, but significant increase was observed with cellulose-diacetate (p<0.001). In patients receiving iron infusion during HD, MDA-formation (n=11) and total DNA damage (n=10) were additionally increased (p<0.005). Our results show an increased oxidative damage in HD-patients, compared to healthy volunteers. Significant influences were found for the dialyser membrane type and iron infusion.     

Trace elements and lipid peroxidation in uremic patients on hemodialysis

Trace elements and lipid peroxidation in 26 patients with chronic renal failure treated with hemodialysis and 25 healthy subjects were observed. Both plasma and erythrocyte trace elements and plasma malon dialdehyde (MDA) were examined immediately before and after hemodialysis. Increased levels of plasma Cu, MDA, and erythrocyte Pb, Mn, Zn, and a significantly decreased plasma Se, Zn and erythrocyte Se were found in patients before hemodialysis. After a single hemodialysis, erythrocyte Mn, Cu, Zn, and plasma Cu, Al, and MDA were significantly increased whereas both plasma and erythrocyte Se were lower in patients than in healthy subjects. The level of MDA was not significantly changed during the single hemodialysis. Both plasma and erythrocyte Zn levels and plasma Cu and Al were significantly higher after hemodialysis than before hemodialysis. In conclusion, levels of trace elements are altered by hemodialysis, which may increase patient susceptibility to lipid peroxidation in uremia.     

Dialyzability and binding of digoxin-like immunoreactive factors (DLIF) with serum macromolecules in uremic patients on hemodialysis

Digoxin-Like Immunoreactive Factors (DLIF) which cross-react with antidigoxin antibodies are present in elevated concentrations in patients on hemodialysis, uremia, hypertensives, liver failure, pre-eclampsia and premature birth. DLIF may have a potential role as a natriuretic hormone with a speculated low molecular weight (less than 1000). We studied the dialyzability and bindings of DLIF with serum components in hemodialysis patients. We analyzed DLIF concentrations in sera and protein free ultrafiltrates of 31 patients and 22 normal volunteers using a fluorescence polarization assay for digoxin. The DLIF concentrations were expressed as nmol/L Digoxin Equivalent. The gel filtration analysis was done using three different Bio-Gel columns with molecular weight cut-offs of 10,000, 20,000 and 40,000. Molecules with lower molecular weight than cut-off were absorbed in the column. Only 3 out of 22 normal volunteers (13.6%) showed measurable DLIF. However 23 out of 31 patients (74.2%) showed measurable DLIF. The concentrations of DLIF were significantly higher in patients with renal failure on hemodialysis (P less than 0.05) by both chi-squared and Fisher's exact test. We observed no statistically significant difference in the concentrations of DLIF in pre and post-dialysis sera, indicating that DLIF were not filtered during hemodialysis. We observed no DLIF activity in the protein free ultrafiltrates of any DLIF positive sera (patients and normal volunteers), indicating that unlike digoxin (where we observed 70-80% of total digoxin concentrations in ultrafiltrates), DLIF were strongly bound to serum components. With Bio-Gel filtration experiments (five different serum pools), we recovered all DLIF activities in the fraction equivalent to the void volume of the column with Bio-Gel P6 and P10 columns, indicating that DLIF were almost completely bound to serum components with molecular weight greater than 20,000. On the other hand, we recovered no DLIF activities in the void volume when the same serum pools were passed through the Bio-Gel P30 column, indicating that DLIF were strongly bound to serum macromolecules with molecular weight less than 40,000. In sharp contrast, when serum containing digoxin was subjected to the same series of experiments, we recovered only 20-30% of digoxin concentrations in void volume with all three columns as expected since digoxin is only 25% bound to albumin (MW 67,000).     

Swelling of olecranon bursa in uremic patients receiving hemodialysis.

Three patients with chronic renal failure who received therapy with hemodialysis through arteriovenous fistulas in the forearm had fluctuating swelling over the elbow on the same side as the fistula used for the dialysis. The clinical findings in each case were compatible with olecranon bursitis with effusion. The aspirate obtained from the swellings contained lymphocytes, polymorphonuclear leukocytes and histiocytes, a finding similar to that in cases of uremic pericardial and pleural effusion. Biopsy of the bursa in one case showed hyalinized collagenous tissue with infiltration by histiocytes and lymphocytes, reflecting underlying chronic inflammation. Uremia was believed to be the causative factor. Bursitis with effusion is considered to be one of the clinical aspects of uremic polyserositis.     

Thyroid function and plasma selenium in chronic uremic patients on hemodialysis treatment

It has been shown recently that Selenium (Se), an essential trace element for humans, is involved in the regulation of thyroid function, since the enzyme that catalyzes the liver conversion of the thyroid hormone T4 to the more active form T3 is a selenoenzyme. In chronic uremic patients, low blood Se levels as well as thyroid function abnormalities are often found. The present study was carried out to verify whether any correlation exists between Se levels and thyroid function, and to evaluate possible changes in hormonal pattern during Se supplementation in 10 chronic uremic patients on hemodialysis (HD) treatment. Se was supplemented orally as sodium selenite over six consecutive months. Basic plasma Se levels were significantly lower in patients than in normal controls. Right from the start of Se supplementation, plasma Se concentration promptly normalized and leveled off in the normal range throughout the study. Significant increase of FT3 and reduction of TSH levels were detected during Se supplementation. In Se-supplemented patients, a significant direct correlation was also found between reverse T3 (rT3) and TSH, and a significant inverse correlation was found between Se and TSH. Our results suggest that Se deficiency in chronic uremic patients represents a factor influencing the thyroid function and that the Se status should be determined in the evaluation of thyroid metabolism in these patients.     

18-Hydroxy-11-deoxycorticosterone in hypertensive uremic patients during hemodialysis.

The present study was carried out in 25 hypertensive uremic patients on regular 4 h dialysis, 3 times a week. Plasma 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), aldosterone (PA) and corticosteroids were determined by radioimmunoassay and competitive protein binding technique before and at the end of the 1st, 2nd and 3rd hour of hemodialysis. Plasma 18-HD-DOC was normal before dialysis and did not change significantly during hemodialysis, whereas body fluids and electolytes decreased progressively. No correlation was observed between blood pressure and 18-OH-DOC during dialysis. 18-OH-DOC did not correlate with PA which decreases progressively during hemodialysis and was correlated to plasma corticosteroids only at the 3rd hour of dialysis, probably on account of the enhanced influence of ACTH on the adrenal cortex.     

Zinc serum level in human immunodeficiency virus-infected patients in relation to immunological status

In human immunodeficiency virus (HIV) infection, serum level of zinc, an important micronutrient for immune function, is frequently diminished. The aim of this study was to determine the zinc status in relation to immunological parameters and disease stage in 79 HIV-1 seropositive patients. The median serum level of zinc was within normal limits (12.5 micromol/L) but in 23% of patients, zinc deficiency was seen. Decreased serum zinc was associated with a low CD4 cell count, high viral load, and increased neopterin and IgA levels. According to current treatment recommendations, the majority of patients received antiretroviral triple therapy. Zinc levels in treated and untreated patients were comparable. Referring to disease stage (CDC classification, 1993), the mean zinc level was highest in stage C and lowest in stage A. In conclusion, even under antiretroviral triple therapy, zinc deficiency is still of great importance in HIV infection, and zinc substitution in zinc deficient individuals should be taken into account to optimize therapeutical success.     

Relationships between the copper and iron systems in hemodialysis patients and variables affecting these systems

The copper-binding protein ceruloplasmin oxidizes ferrous iron to ferric iron, an action that is critical for the binding of iron to transferrin in plasma. Ceruloplasmin, in common with ferritin and transferrin, is an acute-phase protein that is altered by inflammation. We sought to identify interrelationships between the copper and iron systems by measuring copper, ceruloplasmin, ferroxidase, ferritin, transferrin, iron, and iron-binding capacity in a group of hemodialysis patients. We looked for evidence of inflammation and free-radical injury by assaying for protein carbonyl groups, protein pyrrolation, di-tyrosine, and advanced oxidation protein products. Our findings were compatible with an active inflammatory state that affected both iron and copper metabolism. Transferrin levels were low, whereas ceruloplasmin levels were elevated compared to normal. Copper concentration was increased proportional to ceruloplasmin. Several variables including ceruloplasmin and transferrin were observed to correlate significantly with the level of pyrrolated protein. The data suggest that posttranslational modification of circulating proteins may affect their structural, enzymatic, and ligand-binding properties. Abnormalities in copper metabolism and their influence on iron handling in renal failure are complex and will require additional study before their importance can be defined.     

Longitudinal study of serum zinc and copper levels in hemodialysis patients and their relation to biochemical markers

A 6-mo longitudinal study of 48 hemodialysis patients (HPs) with chronic renal failure was performed. Three blood samplings were done. Samples of whole blood from each patient were collected during hemodialysis sessions after passing through the artificial kidney. Zinc and copper levels were measured by atomic absorption spectrometry. Additionally, 36 biochemical indexes were evaluated during the study. Fifty-two healthy matched controls were also considered. Mean serum zinc and copper concentrations in HPs were significantly decreased (Zn) and increased (Cu), when compared with healthy controls (p<0.01). Zinc concentrations found in the first and second blood samplings from patients were significantly lower than those measured for the third sampling (p<0.01). The etiology of chronic renal failure influenced the statistically serum Zn levels of patients (p<0.05). Serum copper levels of HPs were significantly diminished by the existence of secondary associated diseases (p<0.01). Uric acid and parathyroid hormone, and total-cholesterol and glutamic-pyruvic-transaminase levels were significantly (p<0.05) and linearly related with serum zinc and copper concentrations, respectively. From all of indexes, creatinine, direct bilirubin, magnesium, calcium, parathyroid hormone, transferrin, and albumin were statistically modified along the longitudinal study (p<0.05). Transferrin serum levels were significantly diminished in the third blood sampling, indicating the tendency toward anemia in the patients. This result is reinforced by low levels of biochemical and hematological indexes related with iron body staus.     

血浆血管生成素-2与ANCA相关性血管炎疾病活动性的相关性研究

目的探讨血浆血管生成素-2(Ang2)与ANCA相关性血管炎疾病活动的相关关系。方法将我院收治的41例ANCA相关性血管炎患者分为缓解期组(BVAS评分3分,n=18)和活动期组(BVAS评分≥15分,n=23),采用酶联免疫吸附试验(ELISA)比较两组血浆Ang2水平。结果活动期组ANCA相关性血管炎患者血浆Ang2水平明显升高,与缓期解组比较差异有统计学意义(P0.05);血浆Ang2水平与BVAS评分成明显正相关(r=-0.278,P0.01)。结论血浆Ang2有望成为评价ANCA相关性血管炎疾病活动的生物学标记物指标。     

Contrasting effect of hemodialysis and peritoneal dialysis on the inhibition of in vitro calcification by uremic serum

Our findings support the earlier observation of Yendt, Connor and Howard that uremic serum inhibits the calcification of rachitic rat cartilage in vitro. We also confirmed their studies showing that this inhibition is not the consequence of increased levels of serum magnesium or blood urea. In addition, we have shown that aqueous solutions of creatinine and uric acid in concentrations up to 20 mg./100 ml. do not cause any inhibition.Hemodialysis of uremic patients does not change the inhibitory activity of their blood. In contrast, after 24 hours of peritoneal dialysis, the blood of most patients does not inhibit calcification.The inhibitory activity of uremic serum, observed in vitro, may be important in the pathogenesis of osteomalacia in patients with renal failure. Failure of hemodialysis to alter this activity may contribute to the progression of renal osteodystrophy in patients on maintenance hemodialysis.     

口腔细菌与血液透析通路感染的关联性研究

目的 确定血液透析(HD)感染患者中,口腔细菌与血管通路感染之间的关联性。 方法 本研究共收集87例慢性肾病患者的微生物血培养数据进行分析,其中53例为回顾性分析,34例为新怀疑的血管通路感染(前瞻性研究)。本研究回顾性分析的主要结果通过结合病人的病历资料和血液培养微生物鉴定;前瞻性研究的主要结果则主要来自于收治到我院疑似患有血管通路感染的肾透析患者。通过血液培养鉴定造成感染的细菌类型。 结果 导致HD血管通路感染的优势细菌为葡萄球菌和肠球菌。大多数感染发生在血液透析导管。锁骨下静脉通道和颈内静脉通道比其他部位更容易感染。经血液培养鉴定的细菌中没有一种被认为是口腔菌群。 结论 口腔细菌与血液透析患者的血管通路感染没有明显关系。     

The relation between barometric pressure and the incidence of perforated duodenal ulcer

A statistical examination of the relationship between barometric pressure and the incidence of perforated duodenal- and prepyloric ulcer (1953–1968) shows that the velocity of the changes in barometric pressure seems to be the only really important biotropic factor, and that old patients seem more "sensitive" to these changes than young ones, i.e. the faster the changes in barometric pressure the greater the biological effect.

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Zusammenfassung Eine statistische Untersuchung der Beziehung zwischen Luftdruck und der Häufigkeit von perforierten Duodenal- und Präpylorusulcera (1953–1968) ergab, dass die Geschwindigkeit des Luftdruckwechsels der einzig wirklich wichtige biotrope Faktor zu sein scheint. Alte Patienten scheinen empfindlicher zu sein als junge. Je schneller die Luftdruckwechsel sind, desto grösser ist die biologische Wirkung.

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Resume On a recherché s'il existait une relation statistique entre la pression barométrique d'une part et la perforation d'ulcères duodénaux et prépyloriques d'autre part. L'étude couvre la période comprise entre 1953 et 1968. Elle a montré que seule la rapidité d'un changement de pression semble avoir un effet biotropique réellement important. Les patient âgés semblent en outre être plus sensibles au phénomène que les plus jeunes. Plus les changements de pression barométriques sont rapides et plus grand est leur effet biologique.

     

The relation between barometric pressure and the incidence of peripheral arterial embolism

A statistical examination of the relationship between barometric pressure and the incidence of peripheral arterial embolism (PAE) in Fune, Denmark, shows, that the velocity of the changes in barometric pressure seems to be the only really important factor, i.e. the faster the changes in barometric pressure the greater the biological effect.

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Zusammenfassung Eine statistische Auswertung der Beziehung zwischen Luftdruck und der Häufigkeit peripherer Arterienembolie in Füne,Dänemark, zeigt, dass die Geschwindigkeit der Luftdruckwechsel der einzig wichtige Faktor zu sein scheint, d.h. je rascher die Luftdruckwechsel, desto grösser ist die biologische Wirkung.

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Resume L'examen statistique de la relation entre la pression barométrique et la fréquence des embolies artérielles périphériques montre que c'est la rapidité du phénomène météorologique qui semble agir au premier chef. Plus la variation de la pression est rapide et plus l'effet biologique est intense. Les chiffre ayant servi de base à cette étude proviennent de Fune au Danemark.

     

肝移植患者易感烟曲霉菌的致病因素及预防策略

肝移植是治疗终末期肝病的有效手段.而患者术后感染烟曲霉的发生率呈现逐年增高趋势.烟曲霉病与烟曲霉诸多致病因素和机体的防御之间的平衡有关.本文对这些致病因子、防御机制及预防策略进行了综述,为进一步研究烟曲霉病的发病机制和临床干预提供参考资料.     

危重患者感染病原菌的分布及血清降钙素原水平的研究

目的 探讨危重患者感染病原菌的分布及血清降钙素原（PCT）的水平,为临床诊断与治疗提供依据。方法 对167例ICU危重感染患者同时送检的微生物培养和PCT检测的结果进行分析,比较两者间的关系。将微生物培养结果分为阴性组、单一标本阳性组、两种标本阳性组和三种及以上标本阳性组,进一步比较四组间PCT检测结果的差异并分析革兰阴性菌、革兰阳性菌和真菌感染后患者体内PCT的水平。结果 167例危重感染患者微生物培养阳性102例,阳性率为61.1%。PCT检测阳性103例,阳性率为61.7%。两者间无统计学差异（χ2=0.01,P>0.05）。两者联合检测的总阳性率为79.6%。102例微生物培养阳性患者中,PCT为0.57（0.10~131.50）μg/L,高于培养阴性患者[PCT为0.33（0.10~21.85）μg/L,U=8.52,P<0.05]。培养阳性患者中,单一标本阳性的PCT水平相对较低,两种及以上标本阳性的PCT水平相对较高。革兰阴性菌、革兰阳性菌和真菌感染组PCT阳性率分别为70.0%、64.7%和66.7%,混合感染组最高,为87.5%。结论 PCT可用于危重患者感染性疾病的早期预测。加强微生物培养和PCT的联合检测,可促进危重患者感染后的精准诊治。     

Iron metabolism in Trypanosoma lewisi infection: serum iron and serum iron-binding capacity.

Progressive changes in iron levels, total iron binding capacity and hematocrit values in sera of rats infected with Trypanosoma lewisi are described. The host dietary group were: (1) complete or full complement; (2) iron-deficient, and (3) pair-fed or calorically restricted. The hematocrit values of T. lewisi-infected rats given the various diets were not significantly different from those of the controls. The decrease in total iron binding capacity (TIBC) of rats inoculated with T. lewisi and fed complete and pair-fed diets ranged up to 15% over uninfected controls. TIBC levels in rats fed an iron-deficient diet and inoculated with T. lewisi ranged up to 32% over uninfected controls. TIBC levels of deficient infected rats were significantly different from the controls from day 90 to infection to the end of the observation period. Serum iron (SI) values of non-infected rats regardless of dietary regimen showed significantly higher values than T. lewisi-infected animals between days 95 and 120. The average SI value, for this period, in adequately fed control rats was 204 +/- 7 microgram/100 ml as compared to 172 +/- 5 microgram/100 for trypanosome-infected rats. SI levels of rats on a pair-fed diet and infected with T. lewisi decreased to 17% over uninfected controls. SI levels of animals on an iron-deficient diet and infected with T. lewisi decreased up to 76% over uninfected controls.