Stable platinum isotope measurements in presolar nanodiamonds by TEAMS.

Nanodiamonds are stardust grains commonly found in primitive meteorites. They survived the formation of the solar system and kept their own individuality. Measurements of trace-element isotopic signatures in these grains will help understanding heavy element nucleosynthesis in massive stars and dust formation from their ejecta. We have continued previous attempts to search for stable Pt isotope anomalies in nanodiamonds via trace element accelerator mass spectrometry (TEAMS). The installation of a new injector beam line at the VERA facility allowed studying low traces of stable elements in different materials. Moreover, recent experiments showed that VERA provides the required measurement precision together with a low Pt machine background. Here, we observed for the first time an indication for enhancements of 198Pt/195Pt isotope ratios in two diamond residues prepared by different chemical separation techniques from the Allende meteorite. Variations in other isotopic ratios were within analytical uncertainty, and no anomaly was identified in a third diamond fraction.

[Neurotheology: neurobiological models of religious experience]. / Neurotheologie : Neurobiologische Modelle religiöser Erfahrungen.

Religions are evolutionary selected social and cultural phenomena. They represent today belief and normative systems on which the main parts of our culture are based. For a long time religions have been seen as mainly originating from a spectrum of religious experiences. These include a broad spectrum of experiences and are astonishingly widespread in the population. The most consistent and transculturally uniform religious experiences are the mystical experiences. Only these (and the prayer experience) have factually been researched in detail neurobiologically. This article presents a review of empirical results and hypothetical approaches to explain mystical religious experiences neurobiologically. Some of the explanatory hypotheses possess logical evidence, some are even supported by neurobiological studies, but all of them have their pitfalls and are at best partially consistent. One important insight from the evidence reviewed here is that there may be a whole array of different neurophysiological conditions which may result in the same core religious mystical experiences.

PLANETARY SCIENCE: Enhanced: Salty Old Rocks.

Small grains of halite in meteorites are generally interpreted as a sign of the former presence of water. In his Perspective, Ott discusses the unexpected discovery of halites in relatively highly metamorphosed meteorites. According to the age determined by Whitby et al. for halite crystals in one of these meteorites, they are among the oldest known materials in the solar system.

A new type of meteoritic diamond in the enstatite chondrite abee.

Diamonds with delta(13)C values of -2 per mil and less than 50 parts per million (by mass) nitrogen have been isolated from the Abee enstatite chondrite by the same procedure used for concentrating Cdelta, the putative interstellar diamond found ubiquitously in primitive meteorites and characterized by delta(13)C values of -32 to -38 per mil, nitrogen concentrations of 2,000 to 12,500 parts per million, and delta(15)N values of -340 per mil. Because the Abee diamonds have typical solar system isotopic compositions for carbon, nitrogen, and xenon, they are presumably nebular in origin rather than presolar. Their discovery in an unshocked meteorite eliminates the possibility of origins normally invoked to account for diamonds in ureilites and iron meteorites and suggests a low-pressure synthesis. The diamond crystals are approximately 100 nanometers in size, are of an unusual lath shape, and represent approximately 100 parts per million of Abee by mass.

Evolution of light chain deposition disease over 8 years.

A 44-year-old female was diagnosed with proteinuria due to nodular glomerulosclerosis secondary to light chain deposition disease (LCDD). After 6 years, deterioration of kidney function occurred and autologous stem cell transplantation was considered, but the patient refused specific therapies. The disease progressed slowly, over a period of 8 years reaching now chronic renal insufficiency stage 4 with a creatinine clearance of 20 ml/min, in spite of no specific therapy. This case, documented by repeated biopsies, demonstrates the very slow loss of kidney function, suggesting the possibility of conservative treatment strategies without taking the risks of chemotherapy or autologous stem cell transplantation, since no long term follow up data of these therapies are available for LCDD.

A single-center experience with BK virus nephropathy.

BACKGROUND: BK virus nephropathy has an increasing role in renal transplant dysfunction, since new, highly potent immunosuppressive drugs have been introduced into therapy following renal transplantation. Diagnosis of acute impairment of renal transplant function is complicated by difficulty in differentiating BK virus nephropathy from acute rejection. PATIENTS AND METHODS: We retrospectively described the findings and therapeutic approaches of 6 consecutive patients with BK virus nephropathy in our transplantation center (75 - 80 transplantations/ year). BK virus nephropathy was classified according to Drachenberg et al. [2004]. RESULTS: We observed an incidence rate of < 1% for BK nephropathy in our center. Four patients had a pattern B whereas 2 patients revealed a pattern C of BK virus nephropathy. Focal C4d-positive staining of peritubular capillaries were found in 2 of the 6 cases. For earlier detection of BK nephropathy, a diagnostic algorithm for each patient after renal transplantation was established. Urine was continuously monitored by cytology for decoy cells and PCR for BK virus DNA. If PCR was also positive for the BK virus in plasma, biopsy of the renal allograft was performed. Thereby diagnosis could be confirmed sooner. For treatment of BK nephropathy in our center, we reduced immunosuppressive agents and initiated a virustatic treatment with cidofovir in the first 3 cases. However, results were not satisfactory and two allografts were lost. We then reconsidered our therapeutic approach and switched the immunosuppressive treatment to leflunomide with consistent low dose steroids. We use therapeutic drug monitoring for leflunomide and aim at a target level of 40 - 100 microg/ml. We lost no allograft with BK nephropathy since using this therapeutic approach. CONCLUSION: In our center, leflunomide therapy, but not cidofovir, was effective in patients with BK virus nephropathy of the renal allograft.

Bone histomorphometry and biochemical markers of bone turnover in patients with chronic kidney disease Stages 3 - 5.

AIMS: Precise identification of renal osteodystrophy requires bone histomorphometry. Several markers of bone turnover may be useful to predict classification and severity of renal osteodystrophy, but there are only limited data whether these markers correlate with bone histomorphometry. METHODS: In 36 patients with chronic kidney disease (CKD) Stage 3/4 and in 96 patients with CKD Stage 5 bone histomorphometry was performed and renal osteodystrophy was classified according to the standardized international nomenclature. Blood samples were taken at the time of bone biopsy, stored and analyzed at the end of the study. RESULTS: Osteitis fibrosa (OF) was the most frequent histomorphometric form, occurred in 47.2% in CKD Stages 3 - 4 and in 61.4% in CKD Stage 5. There was no difference in the frequency of adynamic renal bone disease (ARBD). The correlation coefficients between bone turnover markers and histomorphometric parameters were higher in CKD 5 patients with high bone turnover lesions. The predictive value for high versus low/normal bone turnover status was comparable for alkaline phosphatase (APH), bone alkaline phosphatase (BAP), pyridinoline (Pyd), desoxypyridinoline (Dpyd), tartrat-resistent acid phosphatase (TRAP Vb) and parathyroid hormone (PTH) in CKD Stage 5 patients, but was insufficient for APH and TRAP Vb in CKD Stage 3 - 4 patients. CONCLUSIONS: Besides parathyroid hormone, biochemical parameters of bone turnover provide a moderate discrimination and prediction of bone turnover status only in patients with CKD Stage 5. Due to a large variability, they are of limited use in predicting the histomorphometric type of renal osteodystrophy. Bone histology remains necessary for an exact classification of underlying pathology.

Anemia after renal transplantation: an underestimated problem.

In end-stage renal disease patients anemia is known to be an independent risk factor for cardiovascular disease and death. In a monocenter retrospective analysis, we investigated 207 stable patients (68 women/139 men) who underwent a first renal transplantation. Immunosuppressive therapy was performed with either cyclosporine plus mycophenolate mofetil, tacrolimus plus mycophenolate mofetil, or rapamycin plus mycophenolate mofetil; 43.5% of the patients were treated with steroids. Seventy-eight patients (37.7%) displayed anemia, including 8.7% with a severe disorder displaying an average hemoglobin (Hb) level of <6.8 mmo/L in men and <6.2 mmol/L in women. In 8.2% of the cases, we observed moderate anemia (Hb 6.8-7.4 mmol/L in men and 6.2-6.8 mmol/L in women), and in 20.8% (29 men and 14 women), mild anemia (Hb <8.06 mmol/L in men and <7.45 mmol/L in women). Erythropoietin was administered in 55.5% of patients with severe anemia, 53% with moderate anemia, and 11.6% with mild anemia. Serum creatinine level was a significant predictor of anemia (B -0.004; SE 0.001; P < .01). Among patients with creatinine >200 micromol/L, 63% were anemic compared with 22% of those with a serum creatinine level <200 micromol/L (P < .05). No correlation was observed with immunosuppressive medication or treatment with angiotensin-converting enzyme inhibitors/angiotensin-II receptor antagonists. During a 3-year follow-up, both mortality and graft failure rates were significantly greater among anemic patients nonanemic patients (mortality 3.3% vs 0.5%, P < .001; graft failure 4.3% vs 0%, P < .001). We found an unexpectedly high incidence of anemia in patients with well-functioning grafts. Anemia as a risk factor for mortality and graft failure should be treated more intensively among renal transplant patients.

Renal retransplantation: a retrospective monocentric study.

Approximately 10% to 20% of all annual renal transplantations are retransplantations and up to 20% of patients on waiting lists need a repeat kidney because of previous graft failure. The immunological risk is much greater among retransplanted patients than first-time kidney recipients. It is likely that retransplantation will become even more prevalent in the future. However, clinical studies or retrospective data are rare in this patient population. We retrospectively investigated 50 recipients after second or third renal transplantations in our center since 2001. Immunosuppression was performed with corticosteroids, mycophenolate mofetil (MMF), tacrolimus, and induction therapy with either thymoglobulin (2.5 mg/kg body weight; n = 27) or 20 mg basiliximab on days 0 and 4 (n = 22) after renal transplantation; 1 patient was treated with antithymoglobulin Fresenius after combined liver-kidney transplantation. Acute rejection occurred in 12 recipients (44.4%) after thymoglobulin and in 7 recipients (31.8%) after basiliximab induction therapy (P < .05). In 4 (14.8%) thymoglobulin- and 5 (22.7%) basiliximab-treated recipients, vascular rejections were observed (P = NS). Patients with basiliximab treatment showed improved renal function at 1 year after transplantation: serum creatinine 134.3 mumol/L versus 199.6 mumol/L in the thymoglobulin group (P < .05). Over the observation period the renal function remained stable or improved in both groups if rejection treatment was successful. However, allograft failure was higher in the basiliximab-treated group, namely, 18.1% versus 14.8% in thymoglobulin-treated patients, but the difference did not reach statistical significance. In 3 (11.1%) thymoglobulin- and 4 (18.2%) basiliximab-treated patients cytomegalovirus (CMV) infections complicated the follow-up (P = NS). In the follow-up period of 5 years, no malignant diseases were seen in either group. Three basiliximab-treated recipients died in the first year due to sepsis or cardiovascular complications. Two thymoglobulin-treated patients developed BK virus nephropathy in the follow-up period. In conclusion, we observed a high immunological risk and rejection risk among retransplanted kidney recipients in our center. Particularly, severe vascular rejections with a harmful long-term impact on allograft function were observed in this population. Induction treatment seems to be successful to reduce risk and achieve better results. Single-shot thymoglobulin may be preferable to reduce severe vascular rejection and prevent allograft failure than basiliximab with the same infection rate.

CYP3A5 genotype markedly influences the pharmacokinetics of tacrolimus and sirolimus in kidney transplant recipients.

It is currently not clear whether the concentration-time curves of the immunosuppressants differ with respect to the CYP3A5, MDR1, or MRP2 genotype in dose-adapted stable kidney transplant patients. Dose/trough concentration ratios were obtained in 134 tacrolimus and 20 sirolimus-treated patients, and plasma concentration-time profiles were obtained from 16 (tacrolimus) and 10 (sirolimus) patients. Genotyping was carried out for CYP3A5 6986A>G; ABCB1 2677G>T/A, 3435C>T and ABCC2 -24C>T; 1249G>A; 3972C>T. Dose/trough concentration ratios were 0.67+/-0.3 and 1.36+/-0.73 x 10(3) l (P<0.00001) for tacrolimus and 0.42+/-0.17 and 0.84+/-0.46 x 10(3) l (P=0.18) for sirolimus in CYP3A5 non-expressors and expressors. The unadjusted tacrolimus area under curve (AUC)(0-12) was 106.8+/-17.5 ng/ml x h compared with 133.3+/-42.2 ng/ml x h (P=0.37) without affecting serum creatinine. Mean unadjusted AUC(0-24) of sirolimus did not differ significantly either. Therefore, CYP3A5 expressor status and not transporter variants is a main determinant of oral clearance, particularly for tacrolimus. Dose adaptation according to trough levels, however, appears to be sufficient to maintain similar concentration-time profiles.

DNA fragmentation in chronic glomerulonephritis: an immunohistological analysis.

BACKGROUND: Experimental data suggest that apoptosis plays an important pathophysiological role in glomerulonephritis by restoring tissue structure after proliferation of intrinsic renal cells and infiltration of leukocytes. Relatively little is known of apoptosis in human glomerulonephritis, particularly in predicting renal function during follow-up. METHODS: In order to colocalize different markers for cell damage in renal tissue from patients with different forms of glomerulonephritis (GN), a series of semithin sections from 34 kidney biopsies were studied retrospectively. Normal kidney from a nephrectomy specimen with a small renal adenocarcinoma served as a control. DNA fragmentation, expression of tissue transglutaminase II, BAX and BCL-2 were visualized immunohistochemically. In some renal biopsies, immunohistochemical staining for activated caspase 3 was performed. Proinflammatory markers (C-reactive protein, leukocytes), serum creatinine, creatinine clearance, total proteinuria, albuminuria, alpha(1)-microglobulin and IgG excretion were determined at the time of biopsy. Serum creatinine and total proteinuria were assessed 6 and 12 months after renal biopsy. RESULTS: Nuclei with different degrees of DNA fragmentation were mainly found in epithelial cells of tubules, but also in glomerular cells, regardless of the form of GN studied. Transglutaminase II expression was found only in cells with a strong staining for DNA fragmentation. DNA fragmentation localized to glomerular cells was more pronounced in proliferative than in non-proliferative forms of GN, being most abundant in patients with rapid progressive GN. Staining for activated caspase 3 in selected biopsies confirmed the presence of apoptosis. BAX and BCL-2 staining was detected within the same cells, but exhibited a different intracellular distribution. In proliferative GN, the extent of DNA damage in tubular epithelial cells significantly corresponds with the concentration of serum creatinine (p < 0.04) and with urinary excretion of alpha(1)-microglobulin (p < 0.01) at the time of biopsy. A significant correlation (p < 0.01) was seen between glomerular DNA fragmentation and follow-up total proteinuria 12 months after biopsy for proliferative forms of GN. The damaged glomerular area (e.g. mesangial sclerosis) significantly correlated with DNA fragmentation in proliferative, but not in nonproliferative GN at the time of biopsy. Furthermore, glomerular damaged showed a significant correlation with tubular DNA damage in proliferative GN. CONCLUSION: In glomerular cells, apoptosis may be important for the clearance of proliferating cells whereas in tubules, cell damage showed dependence on the degree of tubular injury mediated by inflammation and/or proteinuria. Although the degree of apoptosis in tubular cells correlates with serum creatinine in proliferative GN at the time of biopsy, it is of limited use to predict future renal function.

DNA fragmentation in acute and chronic rejection after renal transplantation.

Acute and chronic rejections are important denominators for the long-term function of renal grafts. One important indicator of cell damage is enzymatic DNA fragmentation. To investigate possible mechanisms, the rate of DNA fragmentation (TUNEL staining), the expression of tissue transglutaminase II (a marker of advanced DNA damage), and 8-hydroxy-2'-deoxyguanosine (8-OhdG), an indicator of oxidative injury of nucleic acids, were studied by immunohistochemistry. Semithin sections of renal biopsies revealed 23 patients to show acute interstitial rejections (Banff 97 IA, IB); eight patients, acute vascular rejection (Banff 97 IIA, IIB); and 20 patients, chronic allograft nephropathy (Banff 97 I to III). Correlations were calculated between apoptotic cells and serum creatinine at the time of biopsy and after 6 months. In acute rejection, the proximal tubular cells were apoptotic, particularly in regions with mononuclear infiltrates. In consecutive sections, these apoptotic tubular cells also showed damage by reactive oxygen species (positive 8-OhdG staining). Patients with acute interstitial rejection revealed the highest number of tubular DNA fragmentation (14.9 +/- 10.3) versus chronic allograft nephropathy (9.2 +/- 5.6) as TUNEL-positive cells per 80,000 micro m(2) (P < .05). Patients with acute vascular rejection showed a low degree of tubular apoptosis (6.8 +/- 5.1). There was no significant difference in glomerular DNA fragmentation between acute interstitial and chronic rejections: acute interstitial rejection = 7.1 +/- 5.9 versus chronic allograft nephropathy=6.1 +/- 3.9 TUNEL-positive cells per 80,000 micro m(2). There was a significant negative correlation between the degree of tubular (P < .01) and glomerular (P < .05) apoptosis and the serum creatinine at the time of biopsy as well as after 6 months in all patients irrespective of the Banff class. However, there was heterogeneity in the correlation between renal function and the degree of apoptosis in the glomerular and tubular compartments in the various Banff classes. A positive correlation (P < .01) was observed between the degree of tubular apoptosis and serum creatinine at 6 months after biopsy among patients with acute vascular rejection (Banff 97 IIA, IIB). The present data revealed a high degree of tubular DNA fragmentation associated with oxidative stress in acute interstitial rejection. Nevertheless, apoptosis did not generally negatively influence future renal function and may be important to clear proliferating cells. Apoptosis may also play a different pathophysiological role depending on the type of rejection.

Renal osteodystrophy after successful renal transplantation: a histomorphometric analysis in 57 patients.

Renal transplantation is the treatment of choice for patients with end-stage renal disease. It corrects most of the metabolic abnormalities that cause renal osteodystrophy. Nevertheless, renal osteodystrophy persists in many transplant recipients. The aim of this study was to investigate frequency and histomorphometric pattern of bone disease after renal transplantation. Bone biopsy specimens were taken from the iliac crest of 57 patients, including 28 women (26-70 years old) and 29 men (27-67 years old). Indications for biopsy were hypercalcemia, elevation of parathyroid hormone, and, in 19 cases, without suspected bone abnormalities based on laboratory parameters. The mean time of dialysis prior to renal transplantation was 43 months (range, 6-91 months in women and 10-111 months in men) and the mean interval between transplantation and bone biopsy was 53.5 months (range, 4-191 months in women and 5-90 months in men). Fourteen patients were treated with either 25-hydroxyvitamin D3 and/or 1-alpha hydroxyvitamin D3 or 1,25 dihydroxyvitamin D3, 3 with phosphate-binding agents. The immunosuppression consisted of cyclosporine, azathioprine, and prednisolone. The cumulative dosage of corticosteroids was 5569+/-5305 mg. For static and dynamic histomorphometry, we used American Society of Bone and Mineral Research nomenclature. Mild osteitis fibrosa and osteitis fibrosa, the most frequent forms of renal osteodystrophy, were observed in 13. (22.8%) and 14 patients (24.6%), respectively. Mixed uremic osteodystrophy was found in 7 patients (12.3%), adynamic renal bone disease in 3 patients (5.3%), and osteomalacia in 2 patients (3.5%). In 13 patients (22.8%), reduced bone mass and structural damage without typical signs of renal osteodystrophy, such as endosteal fibrosis or osteoclasia, were detected, and 5 patients (8.7%) showed normal histomorphometric parameters. We concluded that renal osteodystrophy, especially forms with high bone turnover, persisted in many patients after successful renal transplantation. This finding may be due to preexisting conditions, such as duration of dialysis and degree of hyperparathyroidism. Bone disease is increased by corticosteroid and immunosuppressive therapy after renal transplantation and requires close monitoring.

Realization of the sixth modification of guidelines for organ placement in renal transplantation-a single-center experience.

Because of the recommendation of the standing commission on organ transplantation, the Board of Bundesärztekammer agreed to a modification of the guidelines for organ transplantation under section 16 of the transplantation law regarding organs from extended donors who have grave diseases. In our case all patients on our waiting list were contacted to be informed about the guideline changes. Only 6 of 322 patients (1.9%) on our waiting list who were transplantable agreed to allow organ placement from a donor with extended criteria.

Toll homologue expression in the beetle tribolium suggests a different mode of dorsoventral patterning than in drosophila embryos.

The gene Toll (Tl) encodes a maternally supplied interleukin 1 receptor-related transmembrane protein, a key component required to establish dorsoventral polarity in the Drosophila embryo. We have isolated Tl homologs of a primitive dipteran, Clogmia albipunctata, and of the beetle Tribolium castaneum. Tribolium Tl protein (Tl) lacks sequences in the C-terminal portion of the cytoplasmic domains that are conserved in the dipteran homologs. The Tl homolog of Tribolium mediates the ventralizing activity when expressed as a gain-of-function variant in transgenic Drosophila, indicating that the sequences conserved in the Diptera are not essential for Tl signaling. In contrast to Drosophila where Tl gene expression occurs maternally and supplies uniformly distributed Tl in the egg membrane, Tl transcripts form a ventral-to-dorsal gradient in the Tribolium blastoderm stage embryo. This localized expression pattern of Tl transcripts, as compared with the strong maternal and ubiquitous expression in Drosophila and Clogmia embryos, suggests that dorsoventral patterning in long-germ band and short-germ band insects involves the same components but different modes of their action.

A Clinical Trial on Weight Loss among Truck Drivers.

BACKGROUND: The high prevalence of obesity among commercial truck drivers may be related to sedentary nature of the job, lack of healthy eating choices, and lack of exercise. There may be a link between obesity and crash risk, therefore an intervention to reduce obesity in this population is needed. OBJECTIVE: To assess feasibility of a 12-week weight loss intervention for truck drivers with a weight loss goal of 10% of initial body weight. METHODS: Drivers were selected based on age (≥21 years) and body mass index (≥30 kg/m^2). The drivers participated in a before-after clinical trial. The intervention included a 12-week program that provided information on healthy diet and increasing exercise, and telephone-based coaching using SMART goals. Outcomes included change from baseline in reported energy intake, measured weight, waist, hip, and neck circumference, blood pressure, and point of care capillary blood lipids and hemoglobin A1c. Exit interviews were conducted to gain insight into driver opinions on the program features and usefulness. This study was registered with the NIH Clinical Trials Registry, number NCT02348983. RESULTS: 12 of 13 drivers completed the study. Weight loss was statistically significant (p=0.03). Reported energy (p=0.005), total fat consumption (p=0.04), and saturated fat consumption (p=0.02) intake were also lower after the 12-week intervention. Drivers attributed their weight loss to health coaching and suggested a longer intervention so that they could reach their goal and become accustomed to the changes. CONCLUSION: This weight loss intervention is feasible for this difficult population. Additional research is needed to compare this intervention with a control group.

The insula is not specifically involved in disgust processing: an fMRI study.

fMRI studies have shown that the perception of facial disgust expressions specifically activates the insula. The present fMRI study investigated whether this structure is also involved in the processing of visual stimuli depicting non-mimic disgust elicitors compared to fear-inducing and neutral scenes. Twelve female subjects were scanned while viewing alternating blocks of 40 disgust-inducing, 40 fear-inducing and 40 affectively neutral pictures, shown for 1.5 s each. Afterwards, affective ratings were assessed. The disgust pictures, rated as highly repulsive, induced activation in the insula, the amygdala, the orbitofrontal and occipito-temporal cortex. Since during the fear condition the insula was also involved, our findings do not fit the idea of the insula as a specific disgust processor.

Secretion of cytokines by uroepithelial cells stimulated by Escherichia coli and Citrobacter spp.

Urinary tract epithelial cells (T 24/83) are able to express interleukin (IL)-6, IL-8, platelet-derived growth factor (PDGF) and tumour necrosis factor-alpha, but not IL-1 beta, IL-2, IL-4 and IL-10 in response to an infection with uropathogenic bacteria. The process of cytokine secretion is time dependent, with a significant increase in the cytokine activity after 60 min. The expression of virulence factors of the bacteria does not seem to play a role. The interaction between bacterial products (e.g. lipopolysaccharide) and/or bacterial adhesion mediated by adhesins and specific receptor molecules of cell surfaces may be responsible for the activity of mediator protein expression in the epithelial cells. The release of PDGF and IL-8 was found to be higher when due to Escherichia coli HB 101 (rough form) than that caused by other bacterial strains. Citrobacter CB 3009 provoked the highest level of IL-6. The PDGF level correlated significantly with IL-6 and IL-8 values (P<0.001). There was a significant correlation between the time-dependent release of IL-6 and IL-8 (P<0.05). In epithelial cytokine response to bacterial infection, the reaction of the epithelial cells may modify themselves (e.g. internalization of bacteria) and the immuno-regulatory processes that are caused by infection and responsible for parenchymal injury.

Determination of autofluorescence of red blood cells (RbCs) in uremic patients as a marker of oxidative damage.

AIM: It is suggested that the red blood cells (RBCs) of uremic patients have increased oxidative damage. The activities of different antioxidant enzymes and the levels of several antioxidants or lipid peroxidation products in RBCs are usually determined to estimate the oxidative stress in uremia. The autofluorescence of RBCs as measured by flow cytometry is caused by the formation of conjugated Schiff base compounds from aldehydes derived from lipid peroxidation and amino groups of phospholipids or cell proteins, and has been proposed as a marker of oxidative stress. The aim of this study was to evaluate if this method is suitable for estimation of oxidative stress in the RBCs of patients with different degrees of renal insufficiency. PATIENTS AND METHODS: To determine the oxidative damage in RBCs in uremia, the autofluorescence of RBCs was measured by flow cytometry in the following 3 groups of patients: group A: 16 patients with chronic renal failure (CRF); group B: 16 hemodialysis (HD) patients; group C: 16 patients with a well-functioning renal allograft. Twenty-four healthy volunteers served as controls. The basal value of RBC autofluorescence and the autofluorescence of RBCs after oxidative damage by treatment with 0.1 mM hydrogen peroxide (H2O2)/0.7 mM sodium azide were determined. RESULTS: In basal RBC autofluorescence values, no differences were found between the 3 groups and the controls. However, there was a significant correlation between the increase of serum creatinine and RBC autofluorescence in the group of patients with CRF (r = 0.521; p = 0.038). After H2O2 treatment, the RBC autofluorescence rose markedly in all individuals. This increase in RBC autofluorescence was significantly higher in the patients with CRF (p = 0.003) and in the HD patients (p = 0.001) compared to the controls. In contrast, there was no difference in RBC autofluorescence between the patients with renal allograft and the controls after H2O2 treatment. CONCLUSIONS: In conclusion, flow cytometry is a useful tool for determining oxidative damage in RBCs. The RBCs of uremic patients are more susceptible to oxidative damage induced by H2O2, likely caused by diminished antioxidant defense in the RBC membrane. Successful renal transplantation leads to a normal autofluorescence response in the RBCs after H2O2 treatment.