Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury.

Background: New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI) but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma.

Methods: This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010.

Posttranslationally modified proteins as mediators of sustained intestinal inflammation.

Oxidative and carbonyl stress leads to generation of N(epsilon)-carboxymethyllysine-modified proteins (CML-mps), which are known to bind the receptor for advanced glycation end products (RAGE) and induce nuclear factor (NF)-kappaB-dependent proinflammatory gene expression. To determine the impact of CML-mps in vivo, RAGE-dependent sustained NF-kappaB activation was studied in resection gut specimens from patients with inflammatory bowel disease. Inflamed gut biopsy tissue demonstrated a significant up-regulation of RAGE and increased NF-kappaB activation.

Postprandial mononuclear NF-kappaB activation is independent of the AGE-content of a single meal.

Objective: Dietary uptake of Advanced Glycation Endproducts (AGE) is supposed to potentially contribute to inflammatory reactions linked to vascular dysfunction and late diabetic complications. One mechanism by which dietary AGE might exert these effects is by activation of the proinflammatory transcription factor NF-kappa-B. The aim of this study was to analyze the postprandial effects of a casein meal with low or high AGE content on postprandial NF-kappaB activation in peripheral blood mononuclear cells (pBMC) of healthy volunteers.

[Maillard reaction products in food as pro-inflammatory and pro-arteriosclerotic factors of degenerative diseases].

Heating of food induces the formation of Maillard reaction products (MRPs) caused by the reaction of reducing sugars with proteins or amino acids. Analogous reactions occur in the human body, eventually forming "Advanced Glycation Endproducts" (AGEs). AGEs accumulate in aging tissues accelerating degenerative-inflammatory and proliferative processes.

Two immunochemical assays to measure advanced glycation end-products in serum from dialysis patients.

Advanced glycation end-products are uremic toxins that accumulate in the serum and tissues of patients with chronic renal failure. Here, we established two enzyme-linked immunosorbent assays (ELISAs) for N(epsilon)-carboxymethyllysine and imidazolone to analyze advanced glycation end-products in human serum. Both ELISAs detected advanced glycation end-products bound to human serum albumin in a dose-dependent way.

Immunochemical crossreactivity of antibodies specific for "advanced glycation endproducts" with "advanced lipoxidation endproducts".

Antibodies against advanced glycation endproducts (AGEs) are used for their immunohistological localization in tissues, for example in Alzheimer's disease (AD) or diabetes. Many monoclonal and polyclonal antibodies have been used, and their specificity is unknown in most cases. Increased radical production, leading to the formation of lipid-derived reactive carbonyl species, such as malondialdehyde (MDA), acrolein, and glyoxal, is a characteristic aspect of age-related diseases like Alzheimer's disease or diabetic polyneuropathy.

The advanced glycation end-product N epsilon-(carboxymethyl)lysine level is elevated in cerebrospinal fluid of patients with amyotrophic lateral sclerosis.

Oxidative stress is involved in the aetiopathogenesis of amyotrophic lateral sclerosis (ALS), a fatal degenerative disorder. To test whether oxidative stress in ALS is increased and confined to the central nervous system, we have measured the glycoxidation product N(epsilon)-(carboxymethyl)lysine (CML) in serum and cerebrospinal fluid (CSF) samples by means of a novel enzyme immunoassay. Significant increases of CSF/serum ratio of CML in ALS patients (n = 25) as compared to normal controls (n = 20, p = 0.

Determination of glycated nucleobases in human urine by a new monoclonal antibody specific for N2-carboxyethyl-2'-deoxyguanosine.

Sugars and sugar degradation products react in vivo readily with proteins (glycation) resulting in the formation of a heterogeneous group of reaction products, which are called advanced glycation end products (AGEs). AGEs notably change the structure and function of proteins so that extended protein-AGE formation is linked to complications such as nephropathy, atherosclerosis, and cataract. DNA can be glycated in vitro in a similar way as proteins, and the two diastereomers of N(2)-carboxyethyl-2'-deoxyguanosine (CEdG(A,B)) were identified as major DNA AGEs.

Improvement of the quality of diabetes control and decrease in the concentrations of AGE-products in patients with type 1 and insulin-treated type 2 diabetes mellitus: results from a 10 year-prospective, population-based survey on the quality of diabetes care in Germany (JEVIN).

Background: Advanced glycation end (AGE)-products are a complex group of compounds that have been implicated in diabetes related long-term complications. Up to the present only few data exist about serum levels of the AGE-proteins N-epsilon-Carboxymethyllysine (CML) and pentosidine in patients with diabetes mellitus.

Patients And Methods: In the present 10-year, population-based trial of a selection-free cohort of patients with insulin-treated diabetes mellitus, serum CML and pentosidine levels were examined in correlation to the patients' quality of diabetes control and the prevalence of diabetes related long-term complications.

Elevated serum levels of N(epsilon)-carboxymethyl-lysine, an advanced glycation end product, are associated with proliferative diabetic retinopathy and macular oedema.

Aims/hypothesis: Diabetic retinopathy is a frequent microvascular complication. In search of novel risk markers, we analysed the association between serum levels of the major advanced glycation end product N(epsilon)-carboxymethyl-lysine (CML) and prevalence of advanced stages of retinopathy in Type 2 diabetic patients without nephropathy.

Methods: We carried out a case-control study of Type 2 diabetic patients with and without advanced stages of diabetic retinopathy.

Age- and stage-dependent accumulation of advanced glycation end products in intracellular deposits in normal and Alzheimer's disease brains.

In this immunohistochemical study, the age- and stage-dependent accumulation of advanced glycation end-products (AGEs) in Alzheimer's disease (AD) and their relation to the formation of neurofibrillary tangles and neuronal cell death was investigated. For this purpose, the distribution of AGEs in neurons and glia was analyzed in the auditory association area of superior temporal gyrus (Brodmann area 22) of young and old non-demented controls and compared with early- and late-stage AD. A possible co-localization of AGEs with typical hallmarks of AD, such as hyperphosphorylated tau (as a marker for disturbed kinase/phosphatase activity), nNOS (as a marker for nitroxidative stress) and caspase-3 (as a marker of apoptotic cell death), was also investigated.

Advanced glycation end-products in patients with chronic alcohol misuse.

Aims: The aim of our study was to determine serum levels of advanced glycation end-products (AGE) in patients with chronic alcohol misuse and to examine their relationship to markers of nutrition and inflammation.

Methods: The study group consisted of 23 heavy alcohol drinkers treated for chronic alcohol misuse and 22 healthy controls. Studied parameters included AGE (fluorescence, CML - carboxymethyllysine and pentosidine), lipids, glucose, albumin, leptin, prealbumin, C-reactive protein (CRP) and pregnancy-associated plasma protein A (PAPP-A).

Advanced glycation end products and receptor for advanced glycation end products in AA amyloidosis.

Advanced glycation end products (AGEs) may be involved in either amyloidogenesis or complications related to amyloid. We hypothesized that AGEs may influence the pathogenesis of AA amyloidosis, and investigated the spatial and temporal relationship between AGEs, carboxy methyl lysine (CML), the AGE receptor (RAGE), and AA amyloid in humans and mice. Specimens from patients with AL and ATTR amyloidosis served as a control.

Improvement in quality of diabetes control and concentrations of AGE-products in patients with type 1 and insulin-treated type 2 diabetes mellitus studied over a period of 10 years (JEVIN).

Advanced glycation end (AGE)-products, a complex and heterogeneous group of compounds, have been implicated in diabetes-related long-term complications. Up to the present, only few data exist about serum levels of the AGE-proteins N- epsilon -carboxymethyllysine (CML) and pentosidine in selection-free populations of patients with type 1 and insulin-treated type 2 diabetes mellitus. In the present 10-year, population-based trial of patients with insulin-treated diabetes mellitus, serum CML and pentosidine levels were examined in correlation to the patients' quality of diabetes control and the prevalence of diabetes-related long-term complications.

Serum levels of total homocysteine, homocysteine metabolites and of advanced glycation end-products (AGEs) in patients after renal transplantation.

Aims: Hyperhomocysteinemia has been described as an independent risk factor for cardiovascular diseases (CVD) influencing patient outcome. Advanced glycation end-products (AGEs) are involved in the pathogenesis of vascular damage in uremia. This study was undertaken to assess whether high serum levels of total homocysteine (tHcy) with its metabolites methylmalonic acid (MMA), methylcitric acid (MCA) and cystathionine (CYSTA) as well as elevated serum concentrations of the AGEs pentosidine and Nepsilon-carboxymethyllysine (CML) are independent risk factors for CVD, left ventricular hypertrophy (LVH) or hypertension as well as kidney dysfunction in renal transplant recipients (RTR).

Pentosidine and N(epsilon)-(carboxymethyl)-lysine in Alzheimer's disease and vascular dementia.

Increasing evidence suggests an interaction of oxidative stress and the formation of advanced glycation end products (AGE) in the onset and progression of Alzheimer's disease. We studied levels of pentosidine and N(epsilon)-(carboxymethyl)-lysine (CML) in serum and cerebrospinal fluid (CSF) of 15 patients with probable Alzheimer's disease (AD), 20 patients with vascular dementia (VD), and 31 control subjects (14 matched for age, and 17 younger patients). AGE protein concentrations in CSF did not differ within controls when divided into two subgroups by age.

N(epsilon)-(carboxymethyl)lysine levels in patients with type 2 diabetes: role of renal function.

Advanced glycation end products (AGEs) such as N(epsilon)-(carboxymethyl)lysine (CML) have been implicated in the development and progression of diabetic nephropathy. The aim of the present study is to investigate AGE levels in patients with type 2 diabetes with special regard to the role of renal impairment. Serum and urine CML levels (using a newly developed enzyme-linked immunosorbent assay), as well as serum AGE-fluorescence, were measured in 109 patients with type 2 diabetes.

Intradermal administration of GAD & evaluation of diabetes incidence in mice: possible relevance for skin tests in humans.

In vitro cell mediated reactivity to Glutamic Acid Decarboxylase (GAD) has been reported in man and in the non-obese diabetic (NOD) mouse. The demonstration of such reactivity in vivo using GAD in a simple intradermal skin test would be useful for mass screening of subjects at risk of Type 1 diabetes. Such a skin test could be simply applied to the forearm, then signs of local reaction would indicate patients at risk.

Serum concentrations of granulocyte colony-stimulating factor in healthy term and preterm neonates and in those with various diseases including bacterial infections.

The neonate is uniquely susceptible to severe and overwhelming bacterial infections. One of the most important deficits in the neonatal host defense system seems to be a quantitative and qualitative deficiency of the myeloid and the phagocytic system. Future optimal therapy of neonatal sepsis may include the use of adjuvant immunologic therapy.

Human monoclonal islet cell antibodies from a patient with insulin-dependent diabetes mellitus reveal glutamate decarboxylase as the target antigen.

The autoimmune phenomena associated with destruction of the beta cell in pancreatic islets and development of type 1 (insulin-dependent) diabetes mellitus (IDDM) include circulating islet cell antibodies. We have immortalized peripheral blood lymphocytes from prediabetic individuals and patients with newly diagnosed IDDM by Epstein-Barr virus transformation. IgG-positive cells were selected by anti-human IgG-coupled magnetic beads and expanded in cell culture.

Pharmacokinetic and hemostatic properties of the recombinant plasminogen activator bm 06.022 in healthy volunteers.

In a randomized, single-blind, placebo-controlled, cross-over Phase-I study pharmacokinetic and hemostatic properties of BM 06.022 were investigated in seven healthy, male human volunteers. The novel recombinant plasminogen activator BM 06.

Dose-ranging study of the novel recombinant plasminogen activator BM 06.022 in healthy volunteers.

The novel recombinant plasminogen activator BM 06.022 consists of the kringle 2 and protease domains of human tissue-type plasminogen activator and is unglycosylated because of its expression in Escherichia coli cells. Pharmacokinetics for activity and hemostatic effects of BM 06.

New enzyme-linked immunosorbent assay methods for measurement of serum erythropoietin levels and erythropoietin antibodies.

For clinical studies with erythropoietin (EPO), enzyme-linked immunosorbent assays for the determination of EPO and EPO antibodies were developed. Using polyclonal and monoclonal EPO antibodies in a sandwich technique, serum EPO levels greater than 10 pg/ml (corresponding to 1 mU/ml, calibrated with the 2nd WHO IRP EPO) can be determined. In 103 healthy blood donors, a mean (+/- SD) value of 36 +/- 19 pg EPO/ml was found.