Rosemarie Kientsch-Engel

Pentosidine and Nε-(carboxymethyl)-lysine in Alzheimer’s disease and vascular dementia

Abstract 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 e -(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. We found significantly elevated levels of CML in CSF of AD patients and of pentosidine in CSF of patients suffering from vascular dementia when compared to controls. The concentrations of pentosidine and CML in serum apparently did not relate directly to CSF values, suggesting influence of extra-cerebral factors in serum samples. It is concluded that AGE proteins are differentially affected in these types of dementia, depending on the specific neuropathology. Furthermore, measurements of AGE products in vivo should rely on CSF rather than blood samples.

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. Using immunohistochemistry, AGEs, CML, and RAGE were found within amyloid deposits, more commonly in AA amyloid than in AL amyloid and not in ATTR amyloid. Western blotting showed that multiple proteins (between 12 and >60 kd) are modified, but not the AA amyloid fibril protein itself. In the murine model of AA amyloidosis, we found a marked interindividual variability with respect to local and systemic CML levels, as well as to splenic RAGE transcription. Serum levels of CML correlated with the duration of the inflammatory response but not with amounts of splenic RAGE mRNA. Other as yet unidentified variables, especially of the heterogeneous group of AGEs, probably modulate transcription of RAGE and influence amyloidogenesis. CML serum levels, in turn, may prove useful in predicting patients at risk.

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. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), kidney injury molecule 1 (KIM1), and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery. Results Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery) detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83), cystatin C (0.76), MIG (0.74), and L-FAPB (0.73). Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score) predicted the risk for AKI (AUC 0.76 and 0.71) and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers. Conclusions In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed similar discriminative performance to biomarkers. The discriminative performance of both plasma and urine biomarkers was reduced by preexisting chronic kidney disease.

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

ZusammenfassungMaillardprodukte (Maillard Reaction Products; MRPs) entstehen beim Erhitzen von Lebensmitteln durch Reaktion von reduzierenden Zuckern mit Proteinen oder Aminosäuren. Im menschlichen Körper werden über analoge Reaktionswege sog. „Advanced Glycation Endproducts“ (AGEs) gebildet, die sich im Alter in Geweben ablagern und degenerativ-entzündliche und proliferative Prozesse beschleunigen. Auch MRPs aus der Nahrung können—direkt im Darm—entzündliche Prozesse nach ähnlichen Mechanismen auslösen und—nach Resorption—im Körper zu diesen entzündlichen und degenerativen Prozessen beitragen oder sie verstärken. Gut aufgeklärt ist inzwischen der Beitrag von AGEs (und der zusätzliche durch MRPs) bei der Ausbildung von diabetischen Komplikationen wie Nephropathie, Neuropathie, Mikro- und Makroangiopathien. Es ist jedoch weitgehend unbekannt, welche der MRPs oder AGEs genau diese zellulären Prozesse auslösen. So könnte eine detaillierte Kenntnis über die chemischen Strukturen und Wirkungen der einzelnen MRPs helfen, die schädlichen unter ihnen in erhitzten Lebensmitteln zu minimieren. Da MRPs bei der erfolgreichen Vermarktung von Lebensmitteln aufgrund ihrer Eigenschaft als Aroma- und Geschmackskomponenten eine nicht unbedeutende Rolle spielen, ist es umso wichtiger, durch definierte Zubereitungsmethoden neutrale geschmackstragende MRPs zu maximieren und gleichzeitig signalaktive pro-inflammatorische MRPs zu minimieren. Zur quantitativen Bestimmung spezifischer MRPs/AGEs können preiswerte immunologische Messmethoden eingesetzt werden. Im medizinischem Bereich eröffnet die Kenntnis der signalaktiven MRP/AGE-Strukturen die Möglichkeit, deren Konzentrationen in Geweben und Körperflüssigkeiten gezielt zu messen und so ihren Einfluss auf entzündliche und altersbedingte degenerative Prozesse (z. B. diabetische Spätschäden, Arteriosklerose, Neurodegeneration) klinischdiagnostisch abzuklären. Aus pharmakotherapeutischer Sicht könnten dann—nach einer entsprechenden klinisch-chemischen Diagnostik—die sich momentan in der Entwicklung befindenden RAGE-Antagonisten als unterstützende Substanzen bei besonders betroffenen Patientengruppen, wie z. B. älteren Diabetikern und Dialysepatienten, in der Zukunft eine besonders wichtige Rolle spielen.SummaryHeating 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. MRPs present in food can also directly cause inflammatory processes in the intestines and, once absorbed, would support and reinforce any inflammatory and degenerative process occurring in the body. The contribution of AGEs (and additional MRPs) in the development of diabetic complications as well as nephropathy, neuropathy, micro- and macroangiopathies is now well established. Which of the MRPs or AGEs in particular induce these cellular processes is currently unknown. Thus the exact knowledge of the chemical structures of the MRPs could help to minimize the formation of “harmful MRPs” that occur due to heating in food processing. Because MRPs play a decisive role in the successful marketing of edibles due to their characteristics as flavor components, it is important to increase the amount of innocuous and palatable MRPs, and minimize signal active pro-inflammatory MRPs by the use of defined preparation methods. It is practicable to use low-priced immunological methods for the quantitative determination of specific MRPs or AGEs. In the medical area, the knowledge of the signal active MRP/AGE structures provides the opportunity to measure their concentrations in body fluids and tissues and thus determine their influence on inflammatory and age-related degenerative processes (e. g., late diabetic complications, arteriosclerosis, degeneration of neurons). From a clinical perspective, the application of RAGE antagonists after an appropriate chemical diagnosis could be effective in supporting the treatment of affected patient groups, especially older diabetic and dialysis patients.

Maillardprodukte aus Lebensmitteln als pro-entzündliche und pro-arteriosklerotische Faktoren bei degenerativen Erkrankungen

ZusammenfassungMaillardprodukte (Maillard Reaction Products; MRPs) entstehen beim Erhitzen von Lebensmitteln durch Reaktion von reduzierenden Zuckern mit Proteinen oder Aminosäuren. Im menschlichen Körper werden über analoge Reaktionswege sog. „Advanced Glycation Endproducts“ (AGEs) gebildet, die sich im Alter in Geweben ablagern und degenerativ-entzündliche und proliferative Prozesse beschleunigen. Auch MRPs aus der Nahrung können—direkt im Darm—entzündliche Prozesse nach ähnlichen Mechanismen auslösen und—nach Resorption—im Körper zu diesen entzündlichen und degenerativen Prozessen beitragen oder sie verstärken. Gut aufgeklärt ist inzwischen der Beitrag von AGEs (und der zusätzliche durch MRPs) bei der Ausbildung von diabetischen Komplikationen wie Nephropathie, Neuropathie, Mikro- und Makroangiopathien. Es ist jedoch weitgehend unbekannt, welche der MRPs oder AGEs genau diese zellulären Prozesse auslösen. So könnte eine detaillierte Kenntnis über die chemischen Strukturen und Wirkungen der einzelnen MRPs helfen, die schädlichen unter ihnen in erhitzten Lebensmitteln zu minimieren. Da MRPs bei der erfolgreichen Vermarktung von Lebensmitteln aufgrund ihrer Eigenschaft als Aroma- und Geschmackskomponenten eine nicht unbedeutende Rolle spielen, ist es umso wichtiger, durch definierte Zubereitungsmethoden neutrale geschmackstragende MRPs zu maximieren und gleichzeitig signalaktive pro-inflammatorische MRPs zu minimieren. Zur quantitativen Bestimmung spezifischer MRPs/AGEs können preiswerte immunologische Messmethoden eingesetzt werden. Im medizinischem Bereich eröffnet die Kenntnis der signalaktiven MRP/AGE-Strukturen die Möglichkeit, deren Konzentrationen in Geweben und Körperflüssigkeiten gezielt zu messen und so ihren Einfluss auf entzündliche und altersbedingte degenerative Prozesse (z. B. diabetische Spätschäden, Arteriosklerose, Neurodegeneration) klinischdiagnostisch abzuklären. Aus pharmakotherapeutischer Sicht könnten dann—nach einer entsprechenden klinisch-chemischen Diagnostik—die sich momentan in der Entwicklung befindenden RAGE-Antagonisten als unterstützende Substanzen bei besonders betroffenen Patientengruppen, wie z. B. älteren Diabetikern und Dialysepatienten, in der Zukunft eine besonders wichtige Rolle spielen.SummaryHeating 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. MRPs present in food can also directly cause inflammatory processes in the intestines and, once absorbed, would support and reinforce any inflammatory and degenerative process occurring in the body. The contribution of AGEs (and additional MRPs) in the development of diabetic complications as well as nephropathy, neuropathy, micro- and macroangiopathies is now well established. Which of the MRPs or AGEs in particular induce these cellular processes is currently unknown. Thus the exact knowledge of the chemical structures of the MRPs could help to minimize the formation of “harmful MRPs” that occur due to heating in food processing. Because MRPs play a decisive role in the successful marketing of edibles due to their characteristics as flavor components, it is important to increase the amount of innocuous and palatable MRPs, and minimize signal active pro-inflammatory MRPs by the use of defined preparation methods. It is practicable to use low-priced immunological methods for the quantitative determination of specific MRPs or AGEs. In the medical area, the knowledge of the signal active MRP/AGE structures provides the opportunity to measure their concentrations in body fluids and tissues and thus determine their influence on inflammatory and age-related degenerative processes (e. g., late diabetic complications, arteriosclerosis, degeneration of neurons). From a clinical perspective, the application of RAGE antagonists after an appropriate chemical diagnosis could be effective in supporting the treatment of affected patient groups, especially older diabetic and dialysis patients.

Comparative analysis of diagnostic and predictive performance of novel renal biomarkers in plasma and urine of acute kidney injury patients

Intr Renal biomarkers represent an attractive new diagnostic tool which not only implies early diagnosis of AKI, but provides also information about patients at risk for AKI and prediction of adverse clinical outcome parameters like the need for renal replacement therapy, length of stay in ICU and mortality. Biomarker levels in urine however may be altered by intravascular volume availability and chronic renal insufficiency.