[Chronic rhinosinusitis in people with cystic fibrosis-an up-to-date review from the perspective of otorhinolaryngology]. / Chronische Rhinosinusitis bei Menschen mit zystischer Fibrose ­ eine aktuelle Übersicht aus der Perspektive der Hals­, Nasen­, Ohrenheilkunde.

BACKGROUND: Cystic fibrosis (CF) is a complex systemic disease involving numerous organ systems. With improved treatment options and increasing life expectancy of persons with CF (PwCF), extrapulmonary manifestations are coming increasingly into the focus. From birth, almost all PwCF have radiologically detectable pathologies in the upper airways attributable to CF-associated chronic rhinosinusitis (CF-CRS). OBJECTIVE: The aim of this work is to provide an up-to-date overview of CF-CRS from the otorhinolaryngology perspective and to provide the reader with background knowledge and current developments. PATHOPHYSIOLOGY: The cystic fibrosis transmembrane conductance regulator (CFTR) gene defect leads to increased viscosity of sinonasal secretions and reduced mucociliary clearance, causing chronic infection and inflammation in the upper airway segment and, consequently, to CF-CRS. CLINICAL PICTURE AND DIAGNOSTICS: The clinical picture of CF-CRS comprises a wide spectrum from asymptomatic to symptomatic courses. CF-CRS is diagnosed clinically and radiologically. THERAPY: Sinonasal saline irrigation is recommended as a conservative treatment measure. Topical corticosteroids are also commonly used. Surgical therapy is reserved for highly symptomatic treatment-refractory patients without a sufficient response to conservative treatment including CFTR modulator (CFTRm) therapies. Depending on the CFTR mutation, CFTRm therapies are the treatment of choice. They not only improve the pulmonary and gastrointestinal manifestations in PwCF, but also have positive effects on CF-CRS. CONCLUSION: The ENT specialist is part of the interdisciplinary team caring for PwCF. Depending on symptom burden and treatment responsiveness, CF-CRS should be treated conservatively and/or surgically. Modern CFTRm have a positive effect on the clinical course of CF-CRS.

[Cystic fibrosis and computed tomography of the lungs]. / Computertomographie der Lunge bei Mukoviszidose.

With its high detail of morphological changes in lung parenchyma and airways as well as the possibilities for three-dimensional reconstruction, computed tomography (CT) represents a solid tool for the diagnosis and follow-up in patients suffering from cystic fibrosis (CF). Guidelines for standardized CT image acquisition in CF patients are still missing. In the mostly younger CF patients, an important issue is the well-considered use of radiation in CT imaging. The use of intravenous contrast agent is mainly restricted to acute emergency diagnostics. Typical morphological findings in CF lung disease are bronchiectasis, mucus plugging, or signs of decreased ventilation (air trapping) which can be detected with CT even in early stages. Various scoring systems that have become established over time are used to grade disease severity and for structured follow-up, e.g., in clinical research studies. With the technical development of CT, a number of postprocessing software tools were developed to help clinical reporting and overcome interreader differences for a standardized quantification. As an imaging modality free of ionizing radiation, magnetic resonance imaging (MRI) is becoming increasingly important in the diagnosis and follow-up of CF patients and is already frequently a substitute for CT for long-term follow-up at numerous specialized centers.

[Magnetic resonance imaging of the lungs in cystic fibrosis]. / Magnetresonanztomographie der Lunge bei Mukoviszidose.

CLINICAL ISSUE: Disease severity and mortality in patients with cystic fibrosis (CF) is mainly determined by (progressive) pulmonary lung disease. Early diagnosis and therapy are important and of prognostic value to conserve lung function. STANDARD RADIOLOGICAL METHODS: Primary imaging techniques for lung imaging are x­ray and computed tomography (CT) to monitor disease severity and regional distribution. METHODICAL INNOVATIONS: Radiation-free imaging techniques such as magnetic resonance imaging (MRI) have gained interest over the last decade in order to prevent radiation damage. PERFORMANCE: The main findings of CF lung disease are airway wall thickening, bronchiectasis, and mucus plugging, which are found in up to 60% of preschool age children. Pleural abnormalities and consolidations are often associated with pulmonary exacerbation. Young CF patients often show a mosaic pattern as functional changes and also perfusion defects can be seen from birth in 50% of CF patients by contrast-enhanced perfusion imaging, and in up to 90% of adult patients, with varying degrees of severity. Dilated bronchial arteries indicate an increased risk for hemoptysis. ACHIEVEMENTS: Proton MRI is the sole imaging technique that can show structural and functional lung changes in one examination. Structured assessment using a scoring system helps to systematically grade the extent and severity of all CF-associated changes. CONCLUSIONS: Lung MRI for cystic fibrosis has been recently established as a clinical standard examination and is routinely performed at experienced centers. More recently, it has also been used as an endpoint within the framework of clinical studies.

[Diagnostics and management of choanal atresia]. / Diagnostik und Management der Choanalatresie.

Choanal atresia is a rare malformation that represents a special challenge. While bilateral choanal atresia usually needs to be surgically treated within a few days of birth, the intervention for one-sided choanal atresia can be postponed for years. Treatment planning requires adequate imaging (CT or MRI), which also serves to exclude other skull base malformities. Surgical treatment currently focuses on transnasal endoscopic techniques. Simultaneous resection of the parts of the vomer involved in the atresia seems to be important surgical success. Postoperative stenting is still controversially discussed. Postoperative application of corticosteroid nasal sprays and saline nasal rinsing for several weeks is of great importance. Due to the rarity of the diagnosis, the absence of prospective randomized controlled trials does not allow definitive statements regarding the optimal surgical technique or stenting.

[Lung diseases in children]. / Lungenerkrankungen im Kindesalter.

BACKGROUND: Lung diseases belong to the most common acute and chronic childhood diseases. With specific diagnostics and therapy the outcome of many congenital and acquired pulmonary diseases in children and adults can be substantially improved. OBJECTIVE: The aim of this review is the presentation and evaluation of important lung diseases in children taking recent developments into consideration. MATERIAL AND METHODS: This article presents a review of the literature on selected acute and chronic lung diseases in children and adolescents. RESULTS: Acute pneumonia remains one of the most frequent causes of mortality in children worldwide. Antibiotic treatment has reduced the morbidity and mortality in Western industrialized countries; however, the treatment of complications, such as pleural empyema and lung abscesses remains challenging. With a prevalence of 10 %, asthma has evolved into the most common chronic disease in children and adolescents in Germany. Using anti-inflammatory inhalation therapy, effective control of asthma symptoms can be achieved in most patients. Cystic fibrosis (CF) remains the most common fatal inherited disease among Caucasians. More than 90 % of the mortality and morbidity of CF are caused by an early onset and progressive chronic obstructive lung disease. Approval of the first causal mutation-specific pharmacotherapy for a subgroup of patients with CF represents a milestone in individualized therapy of lung diseases. The pathogenesis of other rare chronic lung diseases including interstitial lung diseases (ILD) is still mostly unknown. CONCLUSION: Continuous improvement in the diagnostics and therapy is crucial to further improve the management and outcome of acute and chronic lung diseases in children. Pediatric pulmonology, as an interdisciplinary subspecialty at the interface of pediatrics, pulmonology and infectious diseases, plays a key role in the translation of scientific progress into clinical practice.

Imaging of Cystic Fibrosis Lung Disease and Clinical Interpretation.

UNLABELLED: Progressive lung disease in cystic fibrosis (CF) is the life-limiting factor of this autosomal recessive genetic disorder. Increasing implementation of CF newborn screening allows for a diagnosis even in pre-symptomatic stages. Improvements in therapy have led to a significant improvement in survival, the majority now being of adult age. Imaging provides detailed information on the regional distribution of CF lung disease, hence longitudinal imaging is recommended for disease monitoring in the clinical routine. Chest X-ray (CXR), computed tomography (CT) and magnetic resonance imaging (MRI) are now available as routine modalities, each with individual strengths and drawbacks, which need to be considered when choosing the optimal modality adapted to the clinical situation of the patient. CT stands out with the highest morphological detail and has often been a substitute for CXR for regular severity monitoring at specialized centers. Multidetector CT data can be post-processed with dedicated software for a detailed measurement of airway dimensions and bronchiectasis and potentially a more objective and precise grading of disease severity. However, changing to CT was inseparably accompanied by an increase in radiation exposure of CF patients, a young population with high sensitivity to ionizing radiation and lifetime accumulation of dose. MRI as a cross-sectional imaging modality free of ionizing radiation can depict morphological hallmarks of CF lung disease at lower spatial resolution but excels with comprehensive functional lung imaging, with time-resolved perfusion imaging currently being most valuable. KEY POINTS: • Hallmarks are bronchiectasis, mucus plugging, air trapping, perfusion abnormalities, and emphysema.• Imaging is more sensitive to disease progression than lung function testing.• CT provides the highest morphological detail but is associated with radiation exposure.• MRI shows comparable sensitivity for morphology but excels with additional functional information.• MRI sensitively depicts reversible abnormalities such as mucus plugging and perfusion abnormalities. Citation Format: • Wielpütz MO, Eichinger M, Biederer J et al. Imaging of Cystic Fibrosis Lung Disease and Clinical Interpretation. Fortschr Röntgenstr 2016; 188: 834 - 845.

Cyto- and genotoxic potential of beta-carotene and cleavage products under oxidative stress.

Free radical attack on beta-carotene results in the formation of high amounts of cleavage products with prooxidant activities towards subcellular organelles such as mitochondria, a finding which could provide an explanation for the contradictory results obtained with beta-carotene in clinical efficacy and cancer prevention trials. Since primary hepatocytes proved to be very sensitive indicators for the genotoxic action of suspect mutagens/carcinogens we therefore investigated a beta-carotene cleavage products mixture (CP), apo-8'-beta-carotenal (apo-8') and beta-carotene in the primary rat hepatocyte assay in the presence and absence of oxidative stress provided by hypoxia/reoxygenation (Hy/re). The endpoints tested were: the mitotic indices, the percentages of necrotic and apoptotic cells, micronucleated cells (MN), chromosomal aberrations (CA) and sister chromatid exchanges (SCE). The results obtained indicate a genotoxic potential of both CP and apo-8' already in the concentration range of 100 nM and 1 microM, i.e. at physiologically relevant levels of beta-carotene and beta-carotene breakdown products. In contrast, no significant cytotoxic effects of these substances were observed, nor did beta-carotene induce significant cytotoxic or genotoxic effects at concentrations ranging from 0.01 up to 10 microM. However, when beta-carotene is supplemented during oxidative stress induced by hypoxia/reoxygenation, a dose-dependent increase of CP is observed accompanied by increasing genotoxicity. Furthermore, when beta-carotene cleavage products were supplied during oxidative stress significant additional increases of genotoxic effects were observed, the additional increases indicating an additive effect of both exposures. Summarizing, these results provide strong evidence that beta-carotene breakdown products are responsible for the occurrence of carcinogenic effects found in the Alpha-Tocopherol Beta-carotene-Cancer prevention (ATBC) study and the beta-CArotene and RETinol Efficacy (CARET) Trial.

Effect of carotenoid oxidation products on neutrophil viability and function.

Human neutrophils are short-lived cells that play important roles in host defense and acute inflammation by releasing hydrolytic and cytotoxic proteins and reactive oxygen derivatives. Apoptosis, a physiological mechanism for cell death, regulates both production and survival of neutrophils, representing a basic biological mechanism for this type of cells. Carotenoids may react with toxic oxygen metabolites released by neutrophils to form a multitude of carotenoid cleavage products that exert, in turn, relevant prooxidative biological effects. Recent data suggest that carotenoid oxidation products may affect neutrophil viability and function by exerting proapoptotic activity and interfering with superoxide production by activated cells. The prooxidant and proapoptotic activities of carotenoid oxidation products could account, at least in some cases, for the procancerogenic properties of carotenoid rich diet.

Niemann-Pick Type C-2 Disease: Identification by Analysis of Plasma Cholestane-3ß,5α,6ß-Triol and Further Insight into the Clinical Phenotype.

INTRODUCTION: Niemann-Pick type C disease is a rare disorder caused by impaired intracellular lipid transport due to mutations in either the NPC1 or the NPC2 gene. Ninety-five % of NPC patients show mutations in the NPC1 gene. A much smaller number of patients suffer from NPC2 disease and present respiratory failure as one of the most frequent symptoms. Several plasma oxysterols are highly elevated in NPC1 and can be used as a biomarker in the diagnosis of NPC1. METHODS: Plasma cholestane-3ß,5α,6ß-triol was evaluated as biomarker for NPC2 by GC/MS and LC-MS/MS analysis. The diagnosis was confirmed by Sanger sequencing and filipin staining. RESULTS: We report three NPC2 patients with typical respiratory problems and a detailed description of the nature of the lung disease in one of them. All patients had elevated levels of plasma cholestane-3ß,5α,6ß-triol. In two of these patients, the positive oxysterol result led to a rapid diagnosis of NPC2 by genetic analysis. The phenotype of the third patient has been described previously. In this patient a cholestane-3ß,5α,6ß-triol concentration markedly above the reference range was found. CONCLUSIONS: Measurement of plasma cholestane-3ß,5α,6ß-triol enables to discriminate between controls and NPC1 and NPC2 patients, making it a valuable biomarker for the rapid diagnosis not only for NPC1 but also for NPC2 disease.The measurement of oxysterols should be well kept in mind in the differential diagnosis of lysosomal diseases, as the elevation of oxysterols in plasma may speed up the diagnosis of NPC1 and NPC2.

Absorbance changes of carotenoids in different solvents.

Carotenoids are typically measured in tissues with the high performance liquid chromatography (HPLC) and quantitation is usually done by calibrating with stock solutions in solvents. Four carotenoids including lutein, zeaxanthin, lycopene and beta-carotene were dissolved in hexane and methanol respectively, and their absorbance characteristics were compared. Lutein shows absorbance spectra that are almost independent of solvents at various concentrations. Spectra of zeaxanthin, lycopene and beta-carotene were found to be more solvent-dependent. The absorbance of zeaxanthin at lambda max is about approximately 2 times larger in methanol than in hexane at the higher concentrations, and increased non-linearly with increasing concentration in hexane. The absorbance of lycopene at lambda max in hexane is approximately 4 fold larger than in methanol, but the absorbance of the methanol sample can be recovered by re-extracting this sample in hexane. The absorbance of beta-carotene in hexane is larger than in methanol, and increased linearly with increasing concentration. But beta-carotene showed a non-linear concentration effect in methanol. There are very small variations in lambda max for all four carotenoids between hexane and methanol, due to differences in molar extinction coefficients. The non-linear concentration effects for these carotenoids are probably due to differences in solubility leading to the formation of microcrystals. Thus, care should be taken with quantitation of tissue carotenoid values, when they depend on measurement of concentrations in stock solutions.

Postanoxic formation of aldehydic lipid peroxidation products in human renal tubular cells.

The levels of the aldehydic lipid peroxidation products 4-hydroxynonenal and malondialdehyde and the levels of adenine nucleotides were measured during anoxia/reoxygenation studies with isolated human renal tubular cells in vitro. Energy depletion of renal cells was demonstrated by the decrease of ATP level. ATP could be restored completely and rapidly during postanoxic reoxygenation. 4-Hydroxynonenal and malondialdehyde levels increased during reoxygenation. In parallel, the breakdown of physiological 4-hydroxynonenal levels was estimated. The 4-hydroxynonenal formation rate was estimated from accumulation and metabolic breakdown rates of this compound.

Dose- and wavelength-dependent oxidation of crystallins by UV light--selective recognition and degradation by the 20S proteasome.

The lens of the human eye is a suitable model for age-related alterations at the molecular level. Age-related cataract formation is closely related to the accumulation of oxidatively altered proteins. In this study the influence of UV-A, UV-B, and UV-C irradiation on the proteolytic susceptibility of alpha-, betaL-, and betaH-crystallins by the isolated 20S proteasome was investigated. The proteins were irradiated with 280, 300, and 350 nm monochromatic light. Changes of the physical properties of the crystallins were characterized by absorbance measurements at 280 nm, fluorescence spectra, and SDS-PAGE-electrophoresis. The proteolytic susceptibility of crystallins was maximal after irradiation at 280 nm and three- to fivefold lower at 300 nm. Irradiation at 350 nm was not able to initiate proteolysis, probably due to protein-aggregate formation of higher molecular weight, as shown by SDS-PAGE. The damage of crystallins by UV-C light might be a signal for its proteolytic degradation by the 20S proteasome, whereas UV-B and UV-A do not increase the proteolytic susceptibility to the same extent but promote the formation of crosslinked proteins. Therefore, irradiation with UV, which is not followed by an increase in the proteolytic susceptibility, is accompanied by the formation of crosslinked proteins. It was concluded, that also long UV-B and UV-A may be involved in age-related alterations of the human lens and cataract formation.

Improved antioxidative protection in winter swimmers.

Adaptation to oxidative stress is an improved ability to resist the damaging effects of reactive oxygen species, resulting from pre-exposure to a lower dose. Changes in uric acid and glutathione levels during ice-bathing suggest that the intensive voluntary short-term cold exposure of winter swimming produces oxidative stress. We investigated whether the repeated oxidative stress in winter swimmers results in improved antioxidative adaptation. We obtained venous blood samples from winter swimmers and determined important components of the antioxidative defense system in the erythrocytes or blood plasma: reduced and oxidized glutathione (GSH and GSSG), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (Cat). The control group consisted of healthy people who had never participated in winter swimming. The baseline concentration of GSH and the activities of erythrocytic SOD and Cat, were higher in winter swimmers. We interpret this as an adaptative response to repeated oxidative stress, and postulate it as a new basic molecular mechanism of increased tolerance to environmental stress.

Carotenoid oxidative degradation products inhibit Na+-K+-ATPase.

This study investigates the biological significance of carotenoid oxidation products using inhibition of Na+-K+-ATPase activity as an index. Beta-carotene was completely oxidized by hypochlorous acid and the oxidation products were analyzed by capillary gas-liquid chromatography and high performance liquid chromatography. The Na+-K+-ATPase activity was assayed in the presence of these oxidized carotenoids and was rapidly and potently inhibited. This was demonstrated for a mixture of beta-carotene oxidative breakdown products, beta-Apo-10'-carotenal and retinal. Most of the beta-carotene oxidation products were identified as aldehydic. The concentration of the oxidized carotenoid mixture that inhibited Na+-K+-ATPase activity by 50% (IC50) was equivalent to 10 microM non-degraded beta-carotene, whereas the IC50 for 4-hydroxy-2-nonenal, a major lipid peroxidation product, was 120 microM. Carotenoid oxidation products are more potent inhibitors of Na+-K+-ATPase than 4-hydroxy-2-nonenal. Enzyme activity was only partially restored with hydroxylamine and/or beta-mercaptoethanol. Thus, in vitro binding of carotenoid oxidation products results in strong enzyme inhibition. These data indicate the potential toxicity of oxidative carotenoid metabolites and their activity on key enzyme regulators and signal modulators.

Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes.

BACKGROUND: It has been suggested that eating green leafy vegetables, which are rich in lutein and zeaxanthin, may decrease the risk for age related macular degeneration. The goal of this study was to analyse various fruits and vegetables to establish which ones contain lutein and/or zeaxanthin and can serve as possible dietary supplements for these carotenoids. METHODS: Homogenates of 33 fruits and vegetables, two fruit juices, and egg yolk were used for extraction of the carotenoids with hexane. Measurement of the different carotenoids and their isomers was carried out by high performance liquid chromatography using a single column with an isocratic run, and a diode array detector. RESULTS: Egg yolk and maize (corn) contained the highest mole percentage (% of total) of lutein and zeaxanthin (more than 85% of the total carotenoids). Maize was the vegetable with the highest quantity of lutein (60% of total) and orange pepper was the vegetable with the highest amount of zeaxanthin (37% of total). Substantial amounts of lutein and zeaxanthin (30-50%) were also present in kiwi fruit, grapes, spinach, orange juice, zucchini (or vegetable marrow), and different kinds of squash. The results show that there are fruits and vegetables of various colours with a relatively high content of lutein and zeaxanthin. CONCLUSIONS: Most of the dark green leafy vegetables, previously recommended for a higher intake of lutein and zeaxanthin, have 15-47% of lutein, but a very low content (0-3%) of zeaxanthin. Our study shows that fruits and vegetables of various colours can be consumed to increase dietary intake of lutein and zeaxanthin.

Erythrocyte free radical and energy metabolism.

The erythrocyte is a highly specialized cell whose main functions are oxygen transport and the mediation of carbon dioxide transport. Energy production in the mature erythrocyte depends on glycolysis, with glucose as the principal substrate. Glycolysis and the oxidative pentose phosphate pathway generate NADH and NADPH to reduce methemoglobin, which is being continuously produced, and the antioxidant glutathione, which is present in high concentrations. Red blood cells are equipped with a highly effective antioxidant defense even without the glutathione system. Compared with other cell types, they possess high activities of the most important antioxidant enzymes. Most of the nonenzymatic antioxidant capacity of whole blood is likewise localized in the erythrocytes. Circulating red cells are mobile free radical scavengers and provide antioxidant protection to other tissues and organs. An imbalance between pro-oxidant reactions and antioxidant defense is described in patients with chronic renal failure. Oxidative stress increases as antioxidant defenses are weakened by pro-oxidant hemodialysis factors; it increases further still in renal anemia with a very low red cell count. Thus in terms of free radical metabolism, the only arguments remaining over the complete correction of renal anemia are those in favor, with none against.

Oxidative stress in anemia.

The increased formation of reactive oxygen species under hypoxic conditions often appears paradoxical. A prooxidant shift results from changes in cellular metabolism (especially energy metabolism), higher flux rates in catecholamine metabolism and permanent leukocyte activation. These mechanisms of increased free radical production then find themselves opposed by an antioxidant system that is markedly weakened by anemia. The erythrocytes represent an important component of the antioxidant capacity of blood, comprising in particular intracellular enzymes, e.g. superoxide dismutase and catalase, but also the glutathione system. It is thus possible that some complications of uremia are at least partly due to oxidative stress. These include cardiovascular complications, premature biological aging and increased susceptibility to infection. Strategies to strengthen the complex endogenous free radical defenses can thus be predicted to show long-term benefit. In this context the expansion of EPO therapy may well be a major step in stabilizing free radical metabolism in anemic patients.

Adaptation of glutathion-peroxidase activity to oxidative stress occurs in children but not in adult patients with end-stage renal failure undergoing hemodialysis.

Lipid peroxidation (LPO) products formed after reaction of free radicals with membrane lipids are involved in the pathogenesis of cardiac diseases. Also in patients with end-stage renal disease (ESRD) LPO was shown to be accelerated and concentrations of non-enzymatic antioxidants were measured lower than in control subjects. However, up to now only limited knowledge about the role of antioxidant enzymes was available. Whether or not activity of those antioxidants might be induced due to oxidative stress in ESRD patients is not known. To answer the question the activity of 3 enzymatic antioxidants, superoxide dismutase (SOD), catalase (CAT), and glutathion peroxidase (GPx), was measured in red blood cells of the ESRD patients undergoing hemodialysis (2 groups: children and adults) and matching controls. LPO in these subjects was determined by measurement of the LPO product 4-hydroxynonenal (HNE) in blood plasma. Plasma HNE was significantly increased by factor 3 in both patient groups children and adults compared to the control groups. The activity of the enzymatic antioxidants was measured differently. While SOD was significantly lower in patients (children and adults) than in the matching controls this was not the case for catalase and GPx. While GPx activity in adult patients was comparable to that in the control groups (childrens and adults), the GPx in children with ESRD was almost twice as high than in the other groups. Since children were shown to have higher levels of glutathion, activated GPx might be a sign of adaptation of these children to the increased rate of oxidation.

Oxidation parameters in complete correction of renal anemia.

UNLABELLED: Chronic hemodialysis (HD) patients are more exposed to oxidative stress, with its adverse impact on many cell functions and not least on patient survival. There is evidence that partial correction of renal anemia by erythropoietin (rhEPO) therapy reduces oxidative stress. The aim of this study was to clarify whether complete correction of renal anemia with rhEPO reduces free radical generation in HD patients and increases antioxidant supply. The following parameters: malondialdehyde (MDA), reduced glutathione (GSH) and glutathione disulfide (GSSG) were investigated in patients with a hematocrit (Hct) normalized on rhEPO therapy (Hct > or = 0.4), and compared with those in anemic patients (Hct 0.3 - 0.39 and Hct < 0.3). The groups were similar in age, sex or body weight. Patients with normal Hct were significantly longer in the chronic HD program (74.0 +/- 70.3 vs. 23.0 +/- 30.9 and 30.6 +/- 34.8 months; p < 0.05) and received significantly lower doses of iron (35.7 +/- 19.5 vs. 55.4 +/- 26.0 and 80.0 +/- 47.1 mg/week; p < 0.05) and rhEPO (68.9 +/- 63.6 vs. 106.5 +/- 63.9 and 152.8 +/- 86.0 IU/kg/week; p < 0.05). MDA levels were significantly lower in the group with normal Hct than in the comparison groups (1.54 +/- 0.27 vs. 1.98 +/- 0.52 and 2.23 +/- 0.93 micromol/l; p < 0.01), but did not differ significantly between the anemic groups. GSH and GSSG concentrations corrected for erythrocyte levels showed no significant differences, but whole-blood levels in patients with Hct > or = 0.4 and 0.3 - 0.39 were significantly higher than in patients with Hct < 0.3 (GSH: 0.97 +/- 0.42 vs. 1.03 +/- 0.38 and 0.62 +/- 0.34 micromol/ml; GSSG: 14.57 +/- 6.06 vs 13.07 +/- 5.18 and 7.28 +/- 3.64 micromol/l; p < 0.05). CONCLUSION: After correction of renal anemia, MDA levels are significantly lower - reflecting decreased free radical generation - than in anemic HD patients. Whole-blood antioxidant capacity is significantly increased. Overall, rhEPO therapy has clearly positive effects on free radical metabolism.