Effect of cryopreservation on DNA damage and DNA repair activity in human blood samples in the comet assay.

The comet assay is a commonly used method to determine DNA damage and repair activity in many types of samples. In recent years, the use of the comet assay in human biomonitoring became highly attractive due to its various modified versions, which may be useful to determine individual susceptibility in blood samples. However, in human biomonitoring studies, working with large sample numbers that are acquired over an extended time period requires some additional considerations.

25-hydroxyvitamin d and advanced glycation endproducts in healthy and hypertensive subjects: are there interactions?

Advanced glycation endproducts (AGEs) accumulate during aging. Skin is the single organ of vitamin D synthesis, induced by ultraviolet B light. Accumulation of AGEs in the skin could interfere with synthesis of the vitamin, whereas the microinflammation and oxidative stress (associated with hypovitaminosis D) could amplify both the toxic effects of AGEs and their production.

Neuronal activation in the central nervous system of rats in the initial stage of chronic kidney disease-modulatory effects of losartan and moxonidine.

The effect of mild chronic renal failure (CRF) induced by 4/6-nephrectomy (4/6NX) on central neuronal activations was investigated by c-Fos immunohistochemistry staining and compared to sham-operated rats. In the 4/6 NX rats also the effect of the angiotensin receptor blocker, losartan, and the central sympatholyticum moxonidine was studied for two months. In serial brain sections Fos-immunoreactive neurons were localized and classified semiquantitatively.

High-tone external muscle stimulation in endstage renal disease: effects on quality of life in patients with peripheral neuropathy.

Objective: High-tone external muscle stimulation (HTEMS) has been shown to ameliorate painful peripheral neuropathy of dialysis patients. We hypothesized that HTEMS could also lead to improved parameters of health-related quality of life (HRQOL).

Methods: 25 end-stage renal disease (ESRD) patients (17 men/8 women, mean age 62.

Neuromuscular electrostimulation techniques: historical aspects and current possibilities in treatment of pain and muscle waisting.

Application of electricity for pain treatment dates back to thousands of years BC. The Ancient Egyptians and later the Greeks and Romans recognized that electrical fishes are capable of generating electric shocks for relief of pain. In the 18th and 19th centuries these natural producers of electricity were replaced by man-made electrical devices.

Karl Peter's fundamental contribution to the structural organization of the kidney.

Karl Peter provided the first detailed description of the structure and morphology of the human kidney and defined at least 9 major segments of the tubules. He showed that the nephrons were heterogeneous in their structure and could be divided in 2 categories: the short-looped and the long-looped ones. Peter's scheme of the human nephrons was published in many journals and textbooks.

AT1 receptor antagonist candesartan attenuates genomic damage in peripheral blood lymphocytes of patients on maintenance hemodialysis treatment.

Background: Angiotensin II (ANG II) and advanced glycation end products (AGEs) exert genotoxic effects in vitro which were prevented by the ANG II type 1 (AT1) receptor blocker, candesartan. In end-stage renal disease (ESRD) the incidence of genomic damage is increased. A stimulation of the renin-angiotensin system and accumulation of AGEs could be involved.

Beginning of modern concept of inflammation: the work of Friedrich Daniel von Recklinghausen and Julius Friedrich Cohnheim.

In Rudolf Virchow's concept of inflammation, the basic alterations were derived from connective tissue cells, which underwent a marked metamorphosis. This cell-based and static conception was fundamentally broadened and, in part, refuted in the ensuing decade by 2 of his scholars. Friedrich Daniel von Recklinghausen characterized the pus cells in acute inflammation and made the seminal observation of their contractility and mobility.

Mass-screening for early detection of renal disease: benefits and limitations of self-testing for proteinuria.

Introduction: Chronic kidney diseases are of growing importance for our health system. With regard to the high number of undetected cases, screening programs provide opportunities for an early to detect and treat patients.

Methods: With the support of local newspapers, we performed a mass screening of the citizens of Würzburg, Germany.

Acute phase reaction to gadolinium-DTPA in dialysis patients.

Background: Several late sequelae of the administration of gadolinium (Gd)-containing MRI contrast agents have been described in patients with advanced renal failure. In an observational series, we found a remarkable frequency of peracute reactions after administration of Gd-DTPA used for cardiovascular evaluation before renal transplantation.

Methods: In a 26-month observational period, 13 of 136 haemodialyzed or CAPD patients exhibited onset of fever, chills and nausea within hours after administration of Gd-DTPA peracute.

Use of cinacalcet HCl to achieve the recommended targets of bone metabolism in a patient with therapy-resistant renal hyperparathyroidism.

We report on a patient with end-stage renal disease and severe progressive secondary hyperparathyroidism, whose condition failed to respond to conventional pharmacologic or surgical interventions. Although immunotherapy produced a partial response, it failed to decrease serum parathyroid hormone to the levels recommended by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative clinical practice guidelines. Treatment with a new calcimimetic agent, cinacalcet HCl (Mimpara, Amgen, Munich, Germany), resulted in a rapid decline in elevated parathyroid hormone levels, near normalization of other laboratory markers of bone metabolism, improvement in mobility and skeletal pain caused by renal osteodystrophy, and an increase in body weight.

Benfotiamine reduces genomic damage in peripheral lymphocytes of hemodialysis patients.

Hemodialysis patients have an elevated genomic damage in peripheral blood lymphocytes (PBLs) and an increased cancer incidence, possibly due to accumulation of uremic toxins like advanced glycation end products (AGEs). Because the vitamin B1 prodrug benfotiamine reduces AGE levels in experimental diabetes, and dialysis patients often suffer from vitamin B1 deficiency, we conducted two consecutive studies supplementing hemodialysis patients with benfotiamine. In both studies, genomic damage was measured as micronucleus frequency of PBLs before and at three time-points after initiation of benfotiamine supplementation.

Reduction of the genomic damage level in haemodialysis patients by folic acid and vitamin B12 supplementation.

Background: Cancer incidence and genomic damage of peripheral lymphocytes are elevated in patients with end-stage renal failure. Among other uraemic toxins, homocysteine (Hcy) levels are increased in most of these patients. In healthy individuals, plasma Hcy correlates with the degree of genomic damage observed in peripheral blood lymphocytes (PBL).

Central atrial natriuretic peptide in dehydration.

To test the effect of dehydration on brain atrial natriuretic peptide (ANP) concentrations in areas important to salt appetite, water balance and cardiovascular regulation, we subjected rats to dehydration and rehydration and measured ANP concentration in 18 brain areas, as well as all relevant peripheral parameters. Water deprivation decreased body weight, blood pressure, urine volume, and plasma ANP, while it increased urine and plasma osmolality, angiotensin II, and vasopressin. ANP greatly increased in 17 and 18 brain areas (all cut cerebral cortex) by 24 h.

Using GI-specific patient outcome measures in renal transplant patients: validation of the GSRS and GIQLI.

Introduction: Gastrointestinal (GI) side-effects occur frequently as a result of immunosuppressant regimens used in renal transplant patients. Little effort has been made to quantify the impact of these side-effects on patients' health-related quality of life and symptom severity.

Objective: To assess the psychometric characteristics of two GI-specific outcome instruments (the Gastrointestinal Rating Scale (GSRS) and the Gastrointestinal Quality of Life Index (GIQLI)) for use in post-renal transplant patients.

The contribution of Rudolf Virchow to the concept of inflammation: what is still of importance?

At the beginning of the 19th century, medicine was based largely on speculative and philosophical concepts. The greatest merit of Rudolf Virchow was without doubt a way of thinking based on natural science. In place of the empirical chaos represented by the doctrines of humors and crasis, he created the new paradigm of cellular pathology.

Renal disease in obesity: the need for greater attention.

Excess body weight may be associated with various functional/structural lesions of the kidney. The spectrum ranges from glomerulomegaly with or without focal or segmental glomerulosclerosis, to diabetic nephropathy, to carcinoma of the kidney and nephrolithiasis. The first sign of renal injury is microalbuminuria or frank proteinuria, in particular in the presence of hypertension.

Effect of different hemodialysis regimens on genomic damage in end-stage renal failure.

Patients with end-stage renal disease display enhanced genomic damage that may have pathophysiologic relevance for cancer development and cardiovascular complications. We investigated to what extent the genomic damage in peripheral blood lymphocytes can be modulated #1: by initiation of standard hemodialysis (SHD) in formerly conservatively treated end-stage renal disease patients, #2: by a switch from SHD to hemodiafiltration, and #3: daily dialysis (DHD). Genomic damage was evaluated by the micronuclei (MN) frequency test and the comet assay (CA).

Genomic damage in end-stage renal failure: potential involvement of advanced glycation end products and carbonyl stress.

In patients with chronic renal failure, genomic damage has been shown by numerous biomarkers, such as micronuclei frequency and comet assay (single-cell gel electrophoresis) in peripheral lymphocytes, 8-hydroxy 2'-deoxyguanosine (8-OH-dG) content in leukocytes, mitochondrial DNA deletions in skeletal muscle tissue and hair follicles, as well as in DNA repair mechanisms in freshly isolated lymphocytes after ultraviolet light exposure. In the pathogenesis of DNA damage--besides genetic influences, enhanced reactive oxygen species (ROS), and lipid peroxidation-the genotoxic potential of advanced glycation end products (AGEs) and reactive carbonyl compounds deserve special attention. In fact, reactions of glucose with DNA can lead to mutagenic DNA AGEs.

Georg Ganter--a pioneer of peritoneal dialysis and his tragic academic demise at the hand of the Nazi regime.

First reports in German literature on the effective removal of uremic toxins by means of extracorporeal hemodialysis in bi-nephrectomized, acute uremic dogs were given by Heinrich Necheles and Georg Haas. These methods were viewed with great scepticism by Georg Ganter who criticized in particular the extensive operative procedure by use of the femoral artery and vein, the size and fragility of the dialysers, as well as the potential toxic effects of the anticoagulant hirudin. As an alternative approach, he suggested the use of the peritoneum as an especially large endogenous dialysis membrane.

Effect of dialysis flux and membrane material on dyslipidaemia and inflammation in haemodialysis patients.

Background: Dyslipidaemia, inflammation and oxidative stress are prominent risk factors that potentially cause vascular disease in haemodialysis patients. Dialysis modalities affect uraemic dyslipidaemia, possibly by modifying oxidative stress, but the effects of dialyser flux and membrane material on atherogenic remnant particles and oxidized low-density lipoproteins (LDL) are unknown.

Methods: We performed a randomized crossover study in 36 patients on haemodialysis to analyse the effect of dialyser flux and membrane material on plasma lipids, apolipoproteins and markers of inflammation and oxidative stress.

The central vasopressinergic system in experimental left ventricular hypertrophy and dysfunction.

In the course of cardiac diseases, various neuruhomonal systems in the plasma are activated. So far there have been only isolated results of investigations about the functional state of central neuropeptide systems in cardiac diseases and, in particular, in heart failure. We investigated, therefore, the central vasopressinergic system, an important neuropeptide system in cardiocirculatory regulation in a model of myocardial hypertrophy and left ventricular dysfunction, a model of supravalvular aortic stenosis.

Plasma levels of advanced glycation end products during haemodialysis, haemodiafiltration and haemofiltration: potential importance of dialysate quality.

Background: Advanced glycation end products (AGEs) accumulate in patients with end-stage renal disease (ESRD). The aim of this study was to investigate the potential influence of different modalities of renal replacement therapies on plasma AGE levels.

Methods: The removal of AGEs by high-flux haemodialysis (HD) using standard and ultrapure dialysis fluid (SDF and UDF), by haemodiafiltration (HDF) and by haemofiltration (HF) was studied by fluorescence spectroscopy and by a carboxymethyllysine (CML)-specific ELISA.

Efficacy and safety of a 7.5% icodextrin peritoneal dialysis solution in patients treated with automated peritoneal dialysis.

In a randomized, prospective, multicenter study, we compared the safety, efficacy, and metabolic effects of a 7.5% icodextrin solution (Extraneal) with a 2.27% glucose solution for long dwell exchanges in patients undergoing automated peritoneal dialysis.