Development of Receptor for Advanced Glycation End Products (RAGE) ligands through target directed dynamic combinatorial chemistry: a novel class of possible antagonists.

RAGE is a transmembrane receptor of immunoglobulin family that can bind various endogenous and exogenous ligands, initiating the inflammatory downstream signaling pathways, including inflammaging. Therefore, RAGE represents an attractive drug target for age-related diseases. For the development of small-molecule RAGE antagonists, we employed protein-templated dynamic combinatorial chemistry (ptDCC) using RAGE's VC1 domain as a template, the first application of this approach in the context of RAGE. The affinities of DCC hits were validated using microscale thermophoresis. Subsequent screening against AGE2 (glyceraldehyde-modified AGE)-sRAGE (solubleRAGE) (AGE2-BSA/sRAGE) interaction using ELISA tests led to the identification of antagonists with micromolar potency. Our findings not only demonstrate the successful application of ptDCC on RAGE but also highlight its potential to address the pressing need for alternative strategies for the development of small-molecule RAGE antagonists, an area of research that has experienced a slowdown in recent years.

Biomarkers of disease in human nails: a comprehensive review.

Diagnostic, monitoring, response, predictive, risk, and prognostic biomarkers of disease are all widely studied, for the most part in biological fluids or tissues, but there is steadily growing interest in alternative matrices such as nails. Here we comprehensively review studies dealing with molecular or elemental biomarkers of disease, as opposed to semiological, pharmacological, toxicological, or biomonitoring studies. Nails have a long history of use in medicine as indicators of pathological processes and have also been used extensively as a matrix for monitoring exposure to environmental pollution. Nail clippings are simple to collect noninvasively as well as to transport and store, and the matrix itself is relatively stable. Nails incorporate, and are influenced by, circulating molecules and elements over their several months of growth, and it is widely held that markers of biological processes will remain in the nail, even when their levels in blood have declined. Nails thus offer the possibility to not only look back into a subject's metabolic history but also to study biomarkers of processes that operate over a longer time scale such as the post-translational modification of proteins. Reports on ungual biomarkers of metabolic and endocrine diseases, cancer, and psychological and neurological disorders will be presented, and an overview of the sampling and analytical techniques provided.

Metabolic transit of dietary advanced glycation end-products - the case of NƐ-carboxymethyllysine.

The Maillard reaction, also called glycation, is one of the major chemical reactions responsible for most yellow-to-brown colors and aromas in cooked foods. This reaction between reducing sugars and amino functions on proteins affects not only the flavor of food, but also leads to the formation of an heterogenous group of structurally-modified amino acids. Some of these, known as "advanced glycation end products" (AGEs), have been found in both foods and human biological fluids, tissues and organs. Except for those that are formed over long periods in vivo at 37 °C, AGEs in the body originate from the digestion and absorption of dietary sources. A high or chronic exposure to dietary AGEs (dAGEs) is suspected as potentially detrimental to human health and studies in the field of food safety have begun to focus their attention on the metabolic transit of dAGEs. This review presents some important findings in this field, with a focus on NƐ-carboxymethyllysine, and presents the evidence for and against an association between intake of dAGEs and their presence in the body. New and promising avenues of research are described, and some future directions outlined.

Carnosinase-1 overexpression, but not aerobic exercise training, affects the development of diabetic nephropathy in BTBR ob/ob mice.

Manipulation of circulating histidine-containing dipeptides (HCD) has been shown to affect the development of diabetes and early-stage diabetic nephropathy (DN). The aim of the present study was to investigate whether such interventions, which potentially alter levels of circulating HCD, also affect the development of advanced-stage DN. Two interventions, aerobic exercise training and overexpression of the human carnosinase-1 (hCN1) enzyme, were tested. BTBR ob/ob mice were either subjected to aerobic exercise training (20 wk) or genetically manipulated to overexpress hCN1, and different diabetes- and DN-related markers were compared with control ob/ob and healthy (wild-type) mice. An acute exercise study was performed to elucidate the effect of obesity, acute running, and hCN1 overexpression on plasma HCD levels. Chronic aerobic exercise training did not affect the development of diabetes or DN, but hCN1 overexpression accelerated hyperlipidemia and aggravated the development of albuminuria, mesangial matrix expansion, and glomerular hypertrophy of ob/ob mice. In line, plasma, kidney, and muscle HCD were markedly lower in ob/ob versus wild-type mice, and plasma and kidney HCD in particular were lower in ob/ob hCN1 versus ob/ob mice but were unaffected by aerobic exercise. In conclusion, advanced glomerular damage is accelerated in mice overexpressing the hCN1 enzyme but not protected by chronic exercise training. Interestingly, we showed, for the first time, that the development of DN is closely linked to renal HCD availability. Further research will have to elucidate whether the stimulation of renal HCD levels can be a therapeutic strategy to reduce the risk for developing DN.

The LepRdb/db mice model for studying glycation in the context of diabetes.

BACKGROUND: Early (furosine) and advanced (carboxymethyllysine, CML) products of glycation (AGEs) have been reported as increased in plasma, tissues, and organs of diabetic people, indicating a direct link between glycation and type 2 diabetes (T2D). While murine models present some of the characteristics observed in diabetic humans, their pertinence as models of glycation, particularly for T2D, remains poorly described. The aim of this study was to characterize and compare glycation in several organs of two commonly studied murine models of T2D using stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS). METHODS: Defining parameters of type 2 diabetes including body weight, fasting glycaemia, and glucose intolerance were measured in three different C57BL6 mouse models of T2D-the genetic LepRdb/db (db/db) model and two diet-induced obesity (DIO) models-and their respective controls. Furosine, free, and protein-bound CML were quantified in kidneys, lungs, heart, and liver by LC-MS/MS. RESULTS: The obesity, hyperglycaemia, and glucose intolerance in db/db mice was accompanied by an increase of furosine and protein-bound CML levels in all organs relative to controls. The DIO models took several months to become obese, exhibited less severe hyperglycaemia and glucose intolerance, while glycation products were not significantly different between these groups (with the exception of furosine in liver and CML in lungs). CONCLUSIONS: The db/db model better reflected the characteristics of human T2D compared with the DIO models and exhibited greater formation and accumulation of both furosine and protein-bound CML in all of the organs tested here.

Nutritional evaluation of mixed wheat-faba bean pasta in growing rats: impact of protein source and drying temperature on protein digestibility and retention.

This study aimed to evaluate the nutritional value of pasta enriched with legume or wheat gluten proteins and dried at varying temperature. A total of four isonitrogenous experimental diets were produced using gluten powder/wheat semolina (6/94, g/g) pasta and faba bean flour/wheat semolina (35/65, g/g) pasta dried at either 55°C (GLT and FLT, respectively) or 90°C (FVHT and GVHT, respectively). Experimental diets were fed to ten 1-month-old Wistar rats (body weight=176 (sem 15) g) for 21 d. Growth and nutritional, metabolic and inflammatory markers were measured and compared with an isonitrogenous casein diet (CD). The enrichment with faba bean increased the lysine, threonine and branched amino acids by 97, 23 and 10 %, respectively. Protein utilisation also increased by 75 % (P<0·01) in FLT in comparison to GLT diet, without any effect on the corrected faecal digestibility (P>0·05). Faba bean pasta diets' corrected protein digestibility and utilisation was only 3·5 and 9 %, respectively, lower than the CD. Growth rate, blood composition and muscle weights were not generally different with faba bean pasta diets compared with CD. Corrected protein digestibility was 3 % lower in GVHT than GLT, which may be associated with greater carboxymethyllysine. This study in growing rats clearly indicates improvement in growth performance of rats fed legume-enriched pasta diet compared with rats fed gluten-wheat pasta diet, regardless of pasta drying temperature. This means faba bean flour can be used to improve the protein quality and quantity of pasta.

Kidney, heart and brain: three organs targeted by ageing and glycation.

Advanced glycation end-product (AGE) is the generic term for a heterogeneous group of derivatives arising from a non-enzymatic reaction between reducing sugars and proteins. In recent years, evidence has accumulated that incriminates AGEs in pathogenic processes associated with both chronic hyperglycaemia and age-related diseases. Regardless of their exogenous or endogenous origin, the accumulation of AGEs and their derivatives could promote accelerated ageing by leading to protein modifications and activating several inflammatory signalling pathways via AGE-specific receptors. However, it remains to be demonstrated whether preventing the accumulation of AGEs and their effects is an important therapeutic option for successful ageing. The present review gives an overview of the current knowledge on the pathogenic role of AGEs by focusing on three AGE target organs: kidney, heart and brain. For each of these organs we concentrate on an age-related disease, each of which is a major public health issue: chronic kidney disease, heart dysfunction and neurodegenerative diseases. Even though strong connections have been highlighted between glycation and age-related pathogenesis, causal links still need to be validated. In each case, we report evidence and uncertainties suggested by animal or epidemiological studies on the possible link between pathogenesis and glycation in a chronic hyperglycaemic state, in the absence of diabetes, and with exogenous AGEs alone. Finally, we present some promising anti-AGE strategies that are currently being studied.

Effect of added nitrogen fertilizer on pyrazines of roasted chicory.

BACKGROUND: Coffee substitutes made of roasted chicory are affected by the formation of acrylamide whose main precursor is asparagine. One strategy for limiting the formation of acrylamide is to reduce free asparagine in the chicory roots by lessening the supply of nitrogen in the field. However, decreasing nitrogen fertilizer could affect the formation of the volatile compounds and, consequently, the sensory characteristics of the roasted chicory. The present study aimed to investigate the impact of the nitrogen supply in five commercial varieties on their aroma profile. RESULTS: The addition of 120 kg ha-1 of nitrogen fertilizer in the field resulted in a greater amount of pyrazines in the roasted chicory. Triangle tests were performed to determine the effect of the nitrogen level on the sensory quality of the five varieties. The results revealed that the chicory aroma was modified in two out of five varieties. CONCLUSION: The results of the present study suggest that a strategy aiming to limit the amount of acrylamide could affect the sensory quality of some varieties of chicory. Further acceptance tests need to be conducted to assess the effect (whether favourable or otherwise) on the sensory quality of the coffee substitutes. © 2016 Society of Chemical Industry.

Implication of advanced glycation end products (Ages) and their receptor (Rage) on myocardial contractile and mitochondrial functions.

Advanced glycation end products (AGEs) play an important role for the development and/or progression of cardiovascular diseases, mainly through induction of oxidative stress and inflammation. AGEs are a heterogeneous group of molecules formed by non-enzymatic reaction of reducing sugars with amino acids of proteins, lipids and nucleic acids. AGEs are mainly formed endogenously, while recent studies suggest that diet constitutes an important exogenous source of AGEs. The presence and accumulation of AGEs in various cardiac cell types affect extracellular and intracellular structure and function. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Activation of RAGE by AGEs causes up regulation of the transcription factor nuclear factor-κB and its target genes. of the RAGE engagement stimulates oxidative stress, evokes inflammatory and fibrotic reactions, which all contribute to the development and progression of devastating cardiovascular disorders. This review discusses potential targets of glycation in cardiac cells, and underlying mechanisms that lead to heart failure with special interest on AGE-induced mitochondrial dysfunction in the myocardium.

Towards a Multifunctional Electrochemical Sensing and Niosome Generation Lab-on-Chip Platform Based on a Plug-and-Play Concept.

In this paper, we present a new modular lab on a chip design for multimodal neurotransmitter (NT) sensing and niosome generation based on a plug-and-play concept. This architecture is a first step toward an automated platform for an automated modulation of neurotransmitter concentration to understand and/or treat neurodegenerative diseases. A modular approach has been adopted in order to handle measurement or drug delivery or both measurement and drug delivery simultaneously. The system is composed of three fully independent modules: three-channel peristaltic micropumping system, a three-channel potentiostat and a multi-unit microfluidic system composed of pseudo-Y and cross-shape channels containing a miniature electrode array. The system was wirelessly controlled by a computer interface. The system is compact, with all the microfluidic and sensing components packaged in a 5 cm × 4 cm × 4 cm box. Applied to serotonin, a linear calibration curve down to 0.125 mM, with a limit of detection of 31 µ M was collected at unfunctionalized electrodes. Added sensitivity and selectivity was achieved by incorporating functionalized electrodes for dopamine sensing. Electrode functionalization was achieved with gold nanoparticles and using DNA and o-phenylene diamine polymer. The as-configured platform is demonstrated as a central component toward an "intelligent" drug delivery system based on a feedback loop to monitor drug delivery.

Microorganisms and Maillard reaction products: a review of the literature and recent findings.

Research on the impact of Maillard reaction products (MRPs) on microorganisms has been reported in the literature for the last 60 years. In the current study, the impact of an MRP-rich medium on the growth of three strains of Escherichia coli was measured by comparing two classic methods for studying the growth of bacteria (plate counting and optical density at 600 nm) and by tracing MRP utilisation. Early stage and advanced MRPs in the culture media were assessed by quantifying furosine and N (ε) -carboxymethyllysine (CML) levels, respectively, using chromatographic methods. These measures were performed prior to and during bacterial growth to estimate the potential use of these MRPs by Escherichia coli CIP 54.8. Glucose and lysine, the two MRP precursors used in the MRP-rich medium, were also quantified by chromatographic means. Compared to control media, increased lag phases and decreased growth rates were observed in the MRP-rich medium for two out of the three Escherichia coli strains tested. In contrast, one strain isolated from the faeces of a piglet fed on a MRP-rich diet was not influenced by the presence of MRPs in the medium. Overall, CML as well as the products obtained by the thermal degradation of glucose and lysine, regardless of the Maillard reaction, did not affect the growth of the three strains tested. In addition, no degradation of fructoselysine or CML was found in the presence of Escherichia coli CIP 54.8.

Digestibility of extruded proteins and metabolic transit of N ε -carboxymethyllysine in rats.

Milk proteins are frequently used as supplements in fortified foods. However, processing produces chemical changes which likely affect the nutritional advantage. This study was intended to explore the possible difference in digestibility between extruded and non-extruded caseins and how the dietary N (ε) -carboxymethyllysine (CML) is metabolised. Normal rats were randomized into either an extruded protein diet (EP) or the same with unextruded proteins (UEP), for two periods of 2 weeks at 7 to 9 and 11 to 13 weeks of age. However, no difference in protein digestibility was detected between the two diets, either in young or in adult animals, despite a 9.4-fold higher level of CML and an 8.5-fold higher level of lysinoalanine in the EP than in the UEP. No diet-related changes were observed in plasma CML, either protein bound or free. Amounts of 38 and 48 % of the orally absorbed CML were excreted in urine and faeces, respectively, in UEP-fed rats. Lower rates of excretion were found in the EP-fed rats (23 and 37 %, respectively). A second animal study using a single oral dose of free CML (400 µg/rat) was set up to measure the systemic concentration of CML every hour from 0 to 4 h. It revealed that protein-bound CML was not affected by the oral dose of CML, and the highest free CML level found in the circulation was 600 ng/mL. Extruded proteins, therefore, appear to be well digested, and CML rapidly eliminated. Since its elimination is, however, incomplete, the question of its biodistribution and metabolism remains open.

Monte Carlo modelling of experimental setup used for biodosimetry intercomparison.

When using biodosimetry techniques to assess absorbed dose from an ionising radiation exposure, a calibration curve is required. At Health Canada (HC), these curves are generated for a variety of radiation qualities and assays to translate biological damage into absorbed dose. They are produced by irradiating biological samples in custom-designed water-equivalent phantoms inside a cabinet X-ray machine. In the HC lab, two different phantoms can be used for irradiation that differs in material composition and internal geometry. To ensure consistency, the impact of using the phantoms interchangeably was investigated. This was done through lab measurements and the development of a Monte Carlo (MC) model. Differences up to 6.7% were found between the two experimental setups, indicating the need for careful consideration if using these setups interchangeably in the laboratory. Once validated, the MC model can be used to investigate different aspects of the experimental setup without the need for laboratory measurements.

Health effects of dietary Maillard reaction products: the results of ICARE and other studies.

In food science the Maillard reaction is well known to cause degradation of amino acids and an overall decrease in the nutritional value of foods that have been subjected to heat in processing. There has been evidence more recently of the endogenous formation of some Maillard reaction products (MRPs) in biological systems and their association with pathophysiological conditions including diabetes, renal disease and cardiovascular disease. Several studies have suggested that dietary MRPs increase the in vivo pool of MRPs after intestinal absorption and contribute to the development of diabetes and related complications. This review focuses on the animal and human studies which have assessed the eventual implications of dietary MRPs on human health, highlighting the different diets tested, the experimental designs and the biomarkers selected to estimate the health effects. The results of these studies are compared to those of the recently published ICARE study. In this latter study an accurate determination of the MRP content of the diets was achieved, allowing the calculation of the contribution of individual food groups to daily MRP intakes in a regular western diet.

Study of the urinary and faecal excretion of Nε-carboxymethyllysine in young human volunteers.

The dietary habits of the adolescent population with a high intake of snack and fast foods mean that they consume a high rate of which in turn leads to the development of different degenerative disorders. There are few studies available on MRP absorption and metabolism. We investigated the effects of a MRP-high and a MRP-low diet on carboxymethyllysine (CML) intake and excretion in 11-14 years adolescent males. In a 2-period crossover trial, 20 healthy subjects were randomly assigned to two groups. The first group consumed the MRP-low diet for 2 weeks, observed a 40-day washout period, and then consumed the MRP-high diet for 2 weeks. The second group received the diets in the reverse order. Subjects collected urine and faeces on the last 3 days of each dietary period. The consumption of the MRP-high diet led to a higher CML input (P < 0.05) (11.28 vs. 5.36 mg/day CML for MRP-high and -low diet, respectively). In parallel, the faecal excretion was also greater (P < 0.05) (3.52 vs. 1.23 mg/day CML, respectively) and proportional to the dietary intake. The urinary elimination of CML was not increased significantly when the MRP-high diet was consumed compared to consumption of the MRP-low diet, and was not proportional to the dietary exposure of CML. In conclusion it was shown that CML absorption and faecal excretion were highly influenced by dietary CML levels. Since the compound has long-term effects on health, an excessive intake deserves attention, especially in a population nutritionally at risk as adolescents.

Monte Carlo calculated beam quality correction factors for two cylindrical ionization chambers in photon beams.

PURPOSE: Although several studies provide data for reference dosimetry, the SNC600c and SNC125c ionization chambers (Sun Nuclear Corporation, Melbourne, FL) are in clinical use worldwide for which no beam quality correction factors kQ are available. The goal of this study was to calculate beam quality correction factors kQ for these ionization chambers according to dosimetry protocols TG-51, TRS 398 and DIN 6800-2. METHODS: Monte Carlo simulations using EGSnrc have been performed to calculate the absorbed dose to water and the dose to air within the active volume of ionization chamber models. Both spectra and simulations of beam transport through linear accelerator head models were used as radiation sources for the Monte Carlo calculations. RESULTS: kQ values as a function of the respective beam quality specifier Q were fitted against recommended equations for photon beam dosimetry in the range of 4 MV to 25 MV. The fitting curves through the calculated values showed a root mean square deviation between 0.0010 and 0.0017. CONCLUSIONS: The investigated ionization chamber models (SNC600c, SNC125c) are not included in above mentioned dosimetry protocols, but are in clinical use worldwide. This study covered this knowledge gap and compared the calculated results with published kQ values for similar ionization chambers. Agreements with published data were observed in the 95% confidence interval, confirming the use of data for similar ionization chambers, when there are no kQ values available for a given ionization chamber.

Hibiscus, Rooibos, and Yerba Mate for Healthy Aging: A Review on the Attenuation of In Vitro and In Vivo Markers Related to Oxidative Stress, Glycoxidation, and Neurodegeneration.

The world is currently undergoing a demographic change towards an increasing number of elderly citizens. Aging is characterized by a temporal decline in physiological capacity, and oxidative stress is a hallmark of aging and age-related disorders. Such an oxidative state is linked to a decrease in the effective mechanisms of cellular repair, the incidence of post-translational protein glycation, mitochondrial dysfunction, and neurodegeneration, just to name some of the markers contributing to the establishment of age-related reduction-oxidation, or redox, imbalance. Currently, there are no prescribed therapies to control oxidative stress; however, there are strategies to elevate antioxidant defenses and overcome related health challenges based on the adoption of nutritional therapies. It is well known that herbal teas such, as hibiscus, rooibos, and yerba mate, are important sources of antioxidants, able to prevent some oxidation-related stresses. These plants produce several bioactive metabolites, have a pleasant taste, and a long-lasting history as safe foods. This paper reviews the literature on hibiscus, rooibos, and yerba mate teas in the context of nutritional strategies for the attenuation of oxidative stress-related glycoxidation and neurodegeneration, and, here, Alzheimer's Disease is approached as an example. The focus is given to mechanisms of glycation inhibition, as well as neuroprotective in vitro effects, and, in animal studies, to frame interest in these plants as nutraceutical agents related to current health concerns.

Plasma Levels of Free NƐ-Carboxymethyllysine (CML) after Different Oral Doses of CML in Rats and after the Intake of Different Breakfasts in Humans: Postprandial Plasma Level of sRAGE in Humans.

N-carboxymethyl-lysine (CML) and other dietary advanced glycation end-products (AGEs) are chemically modified amino acids with potential toxicological effects putatively related to their affinity with the receptor for AGEs (RAGE). The goal of this study was to determine the postprandial kinetics of CML in both rodents and humans and, in the latter, to evaluate their relationship with the soluble RAGE isoforms (sRAGE). Four gavage solutions containing different forms of CML were given to rats, and blood was collected over 8 h. Three different breakfasts containing dietary CML (dCML) were administered to 20 healthy volunteers, and blood was collected over 2 h. Concentrations of CML, CEL, and lysine were quantified in plasma and human meals by LC-MS/MS, and sRAGE was determined in human plasma by ELISA. The results showed that dCML did not affect the concentrations of circulating protein-bound CML and that only free CML increased in plasma, with a postprandial peak at 90 to 120 min. In humans, the postprandial plasmatic sRAGE concentration decreased independently of the dAGE content of the breakfasts. This study confirms reports of the inverse postprandial relationship between plasmatic free CML and sRAGE, though this requires further investigation for causality to be established.

High hydrostatic pressure processing of human milk preserves milk oligosaccharides and avoids formation of Maillard reaction products.

BACKGROUND & AIMS: High hydrostatic pressure (HHP) processing is a non-thermal method proposed as an alternative to Holder pasteurization (HoP) for the treatment of human milk. HHP preserves numerous milk bioactive components that are degraded by HoP, but no data are available for milk oligosaccharides (HMOs) or the formation of Maillard reaction products, which may be deleterious for preterm newborns. METHODS: We evaluated the impact of HHP processing of human milk on 22 HMOs measured by liquid chromatography with fluorescence detection and on furosine, lactuloselysine, carboxymethyllysine (CML) and carboxyethyllysine (CEL) measured by liquid chromatography with tandem mass spectrometric detection (LC-MS/MS), four established indicators of the Maillard reaction. Human raw milk was sterilized by HoP (62.5 °C for 30 min) or processed by HHP (350 MPa at 38 °C). RESULTS: Neither HHP nor HoP processing affected the concentration of HMOs, but HoP significantly increased furosine, lactuloselysine, CML and CEL levels in milk. CONCLUSIONS: Our findings demonstrate that HPP treatment preserves HMOs and avoids formation of Maillard reaction products. Our study confirms and extends previous findings that HHP treatment of human milk provides safe milk, with fewer detrimental effects on the biochemically active milk components than HoP.

Technical Note: Implications of using EGSnrc instead of EGS4 for extracting electron stopping powers from measured energy spectra.

PURPOSE: NRC Report PIRS-0626 (https://doi.org/10.4224/40000364) describes how measured electron energy deposition spectra can be used to determine the electronic stopping power. The stopping power is obtained by comparing measured spectra with spectra calculated using Monte Carlo techniques. The stopping powers reported in PIRS-0626 were obtained using the EGS4 Monte Carlo code. Since then, the EGSnrc code has been released which has more accurate electron transport algorithms. We calculate the effect on the measured stopping powers of using EGSnrc instead of EGS4. METHOD: The EGS4 spectra calculated in PIRS-0626 were based on 4 × 10 5 primary electron histories. We first show that those spectra, calculated in 1997, are consistent with current EGS4 spectra calculated using 10 8 histories. EGSnrc spectra are also calculated using 10 8 histories and these high-precision spectra are compared to extract any energy difference. The energy differences between the spectra are used to estimate the effect on the measured electronic stopping powers. RESULTS: The energy differences depend on the absorber material, the absorber thickness and the beam energy. The improved electron elastic scattering cross section of EGSnrc accounts for only part of the difference between the two codes. The effect on the extracted stopping power is largest for the lowest electron energies and can be as large as 0.9%. The calculated spectra show differences for lower energies, with the EGSnrc spectra having a larger proportion of low-energy electrons. CONCLUSION: The differences introduced by using EGSnrc instead of EGS4 can affect the estimated stopping power by almost 1% in the worst case but generally the effect is much smaller. We report corrections that can be applied to all the stopping power data in PIRS-0626. An experiment to measure the average energy to create an ion pair in air, W air , using aluminum detectors will provide an interesting test of the aluminum stopping power data as reported in PIRS-0626 and revised by this work.