Glycated bovine serum albumin for use in feeding trials with animal models - In vitro methodology and characterization of a glycated substrate for modifying feed pellets.

This study investigated different methods to produce Nε-carboxymethyl-lysine (CML)-enriched bovine serum albumin (BSA) as alternatives to the classical approach using glyoxylic acid (GA) and sodium cyanoborohydride (NaBH3CN) which results in toxic hydrogen cyanide (HCN). The reaction of GA (6 mmol/L) and NaBH3CN (21 mmol/L) to produce CML remained the most effective with CML yields of 24-35%, followed by 13-24% using 300 mmol/L glyoxal (GO). GA promoted specific modification of lysine to CML, and fewer structural modifications of the BSA molecule compared with GO, as evidenced by fluorescence and proteomic analyses. GO promoted greater arginine modification compared with GA (76 vs 23%). Despite structural changes to BSA with GO, murine fecal clearance of CML was similar to literature values. Hence, BSA glycation with 300 mmol/L glyoxal is a suitable alternative to GA and NaBH3CN for generating CML-enriched protein free of HCN, but a CML-only fortification model remains to be described.

Semi-industrial production of a minimally processed infant formula powder using membrane filtration.

Infant formula (IF) is submitted to several heat treatments during production, which can lead to denaturation or aggregation of proteins and promote Maillard reaction. The objective of this study was to investigate innovative minimal processing routes for the production of first-age IF powder, thus ensuring microbial safety with minimal level of protein denaturation. Three nutritionally complete IF powders were produced at a semi-industrial scale based on ingredients obtained by fresh bovine milk microfiltration (0.8 and 0.1-µm pore size membranes). Low-temperature vacuum evaporation (50°C) and spray-drying (inlet and outlet temperatures of 160 and 70°C, respectively) were conducted to produce the T- formula with no additional heat treatment. The T+ formula was produced with a moderate heat treatment (75°C for 2 min) applied before spray-drying, whereas the T+++ formula received successive heat treatments (72°C for 30 s on the milk; 90°C for 2-3 s before evaporation; 85°C for 2 min before spray-drying), thus mimicking commercial powdered IF. Protein denaturation and Maillard reaction products were followed throughout the production steps and the physicochemical properties of the powders were characterized. The 3 IF powders presented satisfactory physical properties in terms of aw, free fat content, glass transition temperature, and solubility index, as well as satisfactory bacteriological quality with a total flora <103 cfu/g and an absence of pathogens when a high level of bacteriological quality of the ingredients was ensured. Protein denaturation occurred mostly during the heat treatments of T+ and T+++ and was limited during the spray-drying process. The IF powder produced without heat treatment (T-) presented a protein denaturation extent (6 ± 4%) significantly lower than that in T+++ (58 ± 0%), but not significantly different from that in T+ (10 ± 4%). Although T- tended to contain less Maillard reaction products than T+ and T+++, the Maillard reaction products did not significantly discriminate the infant formulas in the frame of this work. The present study demonstrated the feasibility of producing at a semi-industrial scale an infant formula being bacteriologically safe and containing a high content of native proteins. Application of a moderate heat treatment before spray-drying could further guarantee the microbiological quality of the IF powders while maintaining a low protein denaturation extent. This study opens up new avenues for the production of minimally processed IF powders.

EGSnrc calculation of activity calibration factors for the Vinten ionization chamber.

The National Physical Laboratory Vinten 671 chamber was selected as a proving ground for a new radionuclide source model in the EGSnrc software. The computational Vinten model is validated against measurements of radionuclide artifacts whose activities were determined by absolute methods. The response of the Vinten chamber is first calculated as a function of gamma energy, but more strikingly, an explicit simulation of radionuclide decay was implemented and now permits the direct determination of a calibration factor, including additional effects due to all decay paths of the radionuclide. The Monte Carlo and experimental calibration factors are found to agree at the percent level, in absolute terms.

Carbamylation is a competitor of glycation for protein modification in vivo.

AIM: Chronic kidney disease (CKD) and diabetes mellitus are two diseases that accelerate protein molecular ageing through carbamylation and glycation reactions, characterized by the binding of urea-derived isocyanic acid and of sugars on proteins, respectively. These two reactions target the same protein amino groups and, thus, compete with each other. Such competition may arise especially in diabetic patients with nephropathy. This study aimed to evaluate their potential competitive effects in vitro and under conditions reproducing CKD and/or diabetes in vivo. METHODS: Albumin was incubated in vitro with glucose, urea or cyanate. Carbamylation in vivo was enhanced in normal and diabetic (db/db) mice by either subtotal nephrectomy or cyanate consumption. Homocitrulline, carbamylated haemoglobin and furosine were measured by LC-MS/MS, fructosamine by colorimetric assay and HbA1c by immunological assay. RESULTS: Reciprocal inhibition between carbamylation and glycation was observed during albumin incubations in vitro. Besides, 5 weeks after induction of CKD in vivo, plasma homocitrulline concentrations were similar in both diabetic and non-diabetic mice, whereas fructosamine and HbA1c were decreased (-23% and -42%, respectively) in diabetic mice with CKD compared with only diabetic ones. Fructosamine and HbA1c were also decreased in cyanate-spiked water-drinking mice compared with plain water-drinking diabetic mice. CONCLUSION: Carbamylation competes with glycation in vivo, especially under conditions of high glycation. Thus, the classic markers of glycaemic control should be interpreted with caution in diabetic patients with CKD because of this competitive effect.

Factors Generating Glucose Degradation Products In Sterile Glucose Solutions For Infusion: Statistical Relevance Determination Of Their Impacts.

Sterilising glucose solutions by heat promotes the generation of a large number of glucose degradation products (GDPs). It has been shown that high levels of GDPs may result in Advanced Glycation End products that have an impact on cellular homeostasis and health in general. If data is available for peritoneal dialysis solutions, little has been published for glucose infusion fluids. It is essential to identify the parameters causing the formation of GDPs and so limit the risk of exposing patients to them. After quantifying both 5-hydroxymethyl-2-furfural, considered as an important indicator of degradation, and 2-furaldehyde, an ultimate GDP of one degradation pathway, in marketed solutions, the aim of this work is to build a model integrating all the parameters involved in the formation rates of these two GDPs: supplier, glucose amount, container material, oxygen permeability coefficient and time-lapse since manufacture. Our results show a good logarithmic relationship between GDP formation rates and time-lapse since manufacture for both GDPs. The amount of GDPs in the glucose solutions for infusion depends on the initial glucose amount, the polymer of the container, the time elapsed since manufacturing and the supplier.

Fecal excretion of Maillard reaction products and the gut microbiota composition of rats fed with bread crust or bread crumb.

A comparison between the impacts of advanced (Nε-carboxymethyllysine - CML) and terminal (melanoidins) Maillard reaction products from bread on gut microbiota was carried out in this study. Gut microbiota composition as well as fecal excretion of CML from both bread crust and bread crumb, and of melanoidins from bread crust were assessed on a rodent model. Rats were fed with pellets supplemented or not with 13% of bread crust, bread crumb, a fiber-free bread crust model (glucose, starch and gluten heated together) or a fiber-free-melanoidin-free bread model (glucose-starch and gluten heated separately) for four weeks. These model systems were developed to limit the presence of wheat-native dietary fibers such as cellulose, hemicelluloses and lignin. CML and melanoidins in pellets and feces were evaluated by LC/MS-MS and HPLC/fluorescence respectively, and gut microbiota composition was determined by cultivation and molecular approaches. Diets supplemented with crumb or the fiber-free-melanoidin-free model contained respectively 17% and 64% less melanoidins than their respective controls. A higher excretion of melanoidins was observed for rats fed with crust or bread crust model compared to their controls, confirming that melanoidins are in contact with gut microbiota. No impact of diets was observed on Firmicutes, Bacteroidetes and lactic flora. A decrease of enterobacteria was only observed for rats fed with the diet supplemented with the fiber-free bread crust model. Moreover, a significant increase of bifidobacteria numbers in the presence of crust, crumb and both bread models was observed, showing that this bifidogenic effect of bread is not due to the presence of melanoidins or wheat-native dietary fibers.

[Spinal stereotactic body radiotherapy: French assessment in 2016]. / État des lieux de la radiothérapie en conditions stéréotaxiques vertébrale en France en 2016.

PURPOSE: Stereotactic body radiotherapy to vertebral column remains uncommon practice and only relevant in selected group of patients. The main objective of the study was to describe the current state of medical practices of stereotactic body radiotherapy to vertebral column in France in 2016 and to assess the diversity of practices to identify areas for improvement and establish a common database set for this technique. MATERIALS AND METHODS: A questionnaire was written with contribution of a medical physicist, a radiation oncologist, an information technologist and a radiotherapy resident. The questionnaire was distributed online to a radiation oncologists and a medical physicists partner of selected French radiotherapy specialized centres that provide stereotactic body radiotherapy to vertebral metastasis from April to June 2016. The questionnaire surveyed the following topics: patients' selection, simulation, targeted volume and organs at risk delineation, prescription, dosimetric implementation and image guidance. RESULTS: A total of 31 centres were surveyed. Seventy eight per cent of centres (n=21) completed the questionnaire. The "ideal" patient for spine stereotactic radiotherapy according to these institutions has a good performance status, a long life expectancy, controlled primary tumour with oligometastatic spread. The most prescribed protocol was 30Gy in three fractions. For clinical target volume delineation, about two thirds of centres used the International Spine Radiosurgery Consortium (ISRC) recommendations (Noël G et al.,2006). CONCLUSION: This study identified some consistency of practices in some aspects despite the lack of consensus guidelines. Nevertheless, further studies are needed to establish consensus of planning and treatment.

[Advanced glycation end products: A risk factor for human health]. / Les produits de glycation avancée : un risque pour la santé humaine.

Advanced glycation end products (AGE) result from a chemical reaction between the carbonyl group of reducing sugar and the nucleophilic NH2 of a free amino acid or a protein; lysine and arginine being the main reactive amino acids on proteins. Following this first step, a molecular rearrangement occurs, rearrangement of Amadori resulting to the formation of Maillard products. Glycation can cause the clouding of the lens by inducing reactions crosslinking proteins. Specialized receptors (RAGE, Galectin 3…) bind AGE. The binding to the receptor causes the formation of free radicals, which have a deleterious effect because they are powerful oxidizing agents, but also play the role of intracellular messenger, altering the cell functions. This is especially true at the level of endothelial cells: the attachment of AGE to RAGE receptor causes an increase in vascular permeability. AGE binding to endothelium RAGE and to monocytes-macrophages, led to the production of cytokines, growth factors, to the expression of adhesion molecules, and the production of procoagulant activity. Diabetic retinopathy is related to excessive secretion of vascular growth factor (vascular endothelial growth factor [VEGF]). AGE-RAGE receptor binding causes the synthesis and secretion of VEGF. Increased permeability, facilitation of leukocyte migration, the production of reactive oxygen species, cytokines and VEGF suggest that the AGE could be an element of a cascade of reactions responsible for the diabetic angiopathy and vascular damages observed during aging and chronic renal failure. Balanced diet or some drugs can limit the deleterious effect of AGE.

Agreement between survey data and Régie de l'assurance maladie du Québec (RAMQ) data with respect to the diagnosis of asthma and medical services use for asthma in children.

INTRODUCTION: The goal of this study was to assess the agreement between the results of a respiratory health survey conducted in Montréal on children aged 6 months to 12 years and the Régie de l'assurance maladie du Québec (RAMQ, Quebec health insurance board) database in terms of the diagnosis of asthma and medical services use. A secondary aim was to evaluate the effect of the survey method used (Internet-based survey or telephone survey). METHODS: We assessed whether a diagnosis of asthma was made for 7922 children. In addition, we compared the use of medical services for asthma (emergency department visits and hospitalizations) in the 12 months preceding the survey for the 402 children considered to have asthma, using 2 groups of respiratory diagnoses and 2 data linkage periods. The agreement between the 2 data sources was evaluated using the kappa statistic (κ) and sensitivity and specificity, as well as percentages of agreement, overreporting and under-reporting with respect to health services use. RESULTS: Moderate agreement was found between the 2 data sources (survey and RAMQ data) in terms of the diagnosis of asthma (κ = 0.54 and κ = 0.60 depending on the definition used). Specificity was high (93% and 96%), but sensitivity varied (50% and 65%). Respondents over-reported health services use, resulting in moderate kappa values (0.49 for emergency department visits and 0.48 for hospitalizations). However, when more diagnoses were included in the definition and when the linkage period was extended (15 rather than 12 months), the kappa values increased (0.59 for emergency department visits and 0.64 for hospitalizations) and sensitivity and specificity were high. Slightly higher agreement was obtained for the Internet-based survey relative to the telephone survey. CONCLUSION: The findings validate the use of survey data with respect to the diagnosis of pediatric asthma and major health services use for this disease.

TITRE: Concordance entre les résultats d'une enquête et les données de la Régie de l'assurance maladie du Québec (RAMQ) pour le diagnostic d'asthme et pour l'utilisation des services médicaux pour asthme chez les enfants. INTRODUCTION: L'objectif est d'évaluer la concordance, quant au diagnostic de l'asthme et à l'utilisation des services médicaux, entre les résultats d'une enquête réalisée à Montréal sur la santé respiratoire des enfants de 6 mois à 12 ans et la base de données de la Régie de l'assurance maladie du Québec (RAMQ). Nous avons voulu également évaluer l'effet du mode d'enquête (Internet ou téléphone). MÉTHODOLOGIE: On a mesuré l'existence d'un diagnostic d'asthme pour 7 922 enfants. On a comparé également l'utilisation des services médicaux pour asthme (visites à l'urgence et hospitalisations) dans les douze derniers mois précédant l'enquête pour les 402 enfants considérés comme asthmatiques, à l'aide de deux groupes de diagnostics respiratoires et deux périodes de couplage. La concordance entre les deux sources a été évaluée à l'aide du coefficient kappa de Cohen (κ), de la sensibilité etde la spécificité ainsi qu'enmesurant, pour l'utilisation des services, les proportions d'accord, de sur-déclaration et de sous-déclaration. RÉSULTATS: La concordance entre les deux sources (enquête et RAMQ) est modérée pour le diagnostic d'asthme (κ = 0,54 et κ = 0,60 selon la définition utilisée). La spécificité est élevée (93 % et 96 %) et la sensibilité variable (50 % et 65 %). Il y a une surdéclaration d'utilisation des services par les répondants, avec des coefficients kappa modérés (0,49 pour les visites aux urgences et 0,48 pour les hospitalisations), mais ces derniers augmentent lorsque l'on inclut davantage de diagnostics dans la définition et que l'on allonge (à 15 mois plutôt que 12) la période de couplage (0,59 pour les visites et 0,64 pour les hospitalisations). La sensibilité et la spécificité sont élevées. La concordance est légèrement plus élevée pour l'enquête par Internet que par téléphone. CONCLUSION: Ces résultats valident l'utilisation des données d'enquête concernant l'asthme pédiatrique et l'utilisation des services principaux en relation avec cette maladie.

On the correction, perturbation and modification of small field detectors in relative dosimetry.

The purpose of this study was to derive a complete set of correction and perturbation factors for output factors (OF) and dose profiles. Modern small field detectors were investigated including a plastic scintillator (Exradin W1, SI), a liquid ionization chamber (microLion 31018, PTW), an unshielded diode (Exradin D1V, SI) and a synthetic diamond (microDiamond 60019, PTW). A Monte Carlo (MC) beam model was commissioned for use in small fields following two commissioning procedures: (1) using intermediate and moderately small fields (down to 2 × 2 cm(2)) and (2) using only small fields (0.5 × 0.5 cm(2) -2 × 2 cm(2)). In the latter case the detectors were explicitly modelled in the dose calculation. The commissioned model was used to derive the correction and perturbation factors with respect to a small point in water as suggested by the Alfonso formalism. In MC calculations the design of two detectors was modified in order to minimize or eliminate the corrections needed. The results of this study indicate that a commissioning process using large fields does not lead to an accurate estimation of the source size, even if a 2 × 2 cm(2) field is included. Furthermore, the detector should be explicitly modelled in the calculations. On the output factors, the scintillator W1 needed the smallest correction (+0.6%), followed by the microDiamond (+1.3%). Larger corrections were observed for the microLion (+2.4%) and diode D1V (-2.4%). On the profiles, significant corrections were observed out of the field on the gradient and tail regions. The scintillator needed the smallest corrections (-4%), followed by the microDiamond (-11%), diode D1V (+13%) and microLion (-15%). The major perturbations reported were due to volume averaging and high density materials that surround the active volumes. These effects presented opposite trends in both OF and profiles. By decreasing the radius of the microLion to 0.85 mm we could modify the volume averaging effect in order to achieve a discrepancy less than 1% for OF and 5% for profiles compared to water. Similar results were observed for the diode D1V if the radius was increased to 1 mm.

A flavonoid fraction purified from Rutaceae aurantiae (Daflon(R)) inhibiting AGE formation, reduces urinary albumin clearance and corrects hypoalbuminemia in normotensive and hypertensive diabetic rats.

AIM: Advanced glycation endproducts (AGEs) have been shown to contribute to alteration of glomerular permselectivity to proteins in diabetes. Oxidative stress is required for AGE formation. Therefore we studied the effect of an antioxidant micronized purified flavonoid fraction (MPFF, Daflon(R) 500 mg), on urinary albumin clearance in diabetic rats. METHODS: Hyperglycaemia was induced by streptozotocin 55 mg/kg IM at days 0 and 7 in normotensive Wistar rats (NWR, diabetes duration 5 months) or hypertensive Wistar Kyoto rats (SHR, diabetes duration 2 months). MPFF was administered at 300 mg/kg/day, from day -2 until sacrifice. RESULTS: After 5 months of diabetes in NWR, MPFF reduced albumin clearance from 729±92 to 392±60 nl/min/kg, p<0.01, and restored albuminemia from 20.4±0.9 to 24.0±1 g/l, p<0.05; albumin fractional clearance was significantly diminished in the flavonoid-treated diabetic rats (0.360±0.037‰ versus 1.335±0.430‰ in the diabetic controls, p<0.001); MPFF did not significantly modify blood glucose and plasma fructosamine levels. After 2 months of diabetes in SHR, MPFF reduced albumin clearance from 243±121 to 101±47 nl/min/kg, p<0.05, and restored albuminemia from 21.1±1.6 to 26.7±2.2 g/l (p<0.05); MPFF also decreased plasma fluorescence characteristic of AGEs (p<0.02). Besides hesperetin, a main metabolite of MPFF recovered in plasma, inhibited in vitro the formation of the crosslinking AGE pentosidine in collagen incubated with high glucose (p<0.001). CONCLUSION: Our results confirm the role of glycoxidative stress in diabetic nephropathy. MPFF might be useful as complementary treatment for preventing diabetic microangiopathy.

Radiation shielding materials and radiation scatter effects for interventional radiology (IR) physicians.

PURPOSE: To measure the attenuation effectiveness and minimize the weight of new non-Pb radiation shielding materials used for radiation protection by interventional radiology (IR) physicians, to compare the accuracy of the different standard measurement geometries of these materials, and to determine x-ray qualities that correspond to the scattered radiation that IR physicians typically encounter. METHODS: Radiation attenuation capabilities of non-Pb materials were investigated. Typically, most studies of non-Pb materials have focused on the attenuating properties of metal powders. In this study, layers of materials incorporating non-Pb powdered compounds such as Bi(2)O(3), Gd(2)O(3), and BaSO(4) were measured individually, as bilayers, and as a Bi(2)O(3)-loaded hand cream. Attenuation measurements were performed in narrow-beam (fluorescence excluded) and broad beam (fluorescence included) geometries, demonstrating that these different geometries provided significantly different results. The Monte Carlo (MC) program EGSnrc was used to calculate the resulting spectra after attenuation by radiation shielding materials, and scattered x-ray spectra after 90° scattering of eight ASTM Standard primary x-ray beams. Surrogate x-ray qualities that corresponded to these scattered spectra were tabulated. RESULTS: Radiation shielding materials incorporating Bi(2)O(3) were found to provide equivalent or superior attenuation compared with commercial Pb-based and non-Pb materials across the 60-130 kVp energy range. Measurements were made for single layers of the Bi(2)O(3) compound and for bilayers where the ordering was low atomic number (Z) layer closest to x-ray source∕high Z (Bi(2)O(3)) layer farthest from the x-ray source. Narrow-beam Standard test methods which do not include the contribution from fluorescence overestimated the attenuating capabilities of Pb and non-Pb materials. Measurements of a newly developed, quick-drying, and easily removable Bi(2)O(3)-loaded hand cream demonstrated better attenuation capabilities than commercial Bi(2)O(3)-loaded gloves. Scattered radiation measurements and MC simulations illustrated that the spectra resulting from 90° scattering of primary x-ray beam qualities can be approximated by surrogate x-ray qualities which are more representative of the radiation actually encountered by IR physicians. A table of surrogate qualities of the eight ASTM F2547-06 Standard qualities was compiled. CONCLUSIONS: New non-Pb compound materials, particularly single layers or bilayers incorporating Bi(2)O(3), can reduce the weight of radiation protection materials while providing equivalent or better protection compared to Pb-based materials. Attenuation measurements in geometries that exclude the contribution from fluorescence substantially underestimate the quantity of transmitted radiation. A new Bi(2)O(3)-loaded hand cream demonstrated a novel and effective approach for hand protection. Standard testing protocols for radiation protection materials used by IR physicians specify a wider kVp range than is necessary. A more realistic range would acknowledge the lower kVp resulting from scatter and allow IR physicians to confidently utilize lighter-weight materials while still receiving adequate protection. Standards protocols incorporating the adjustments described in this work would maintain the safety of IR personnel and lessen the physical repercussions of long hours wearing unnecessarily heavy radiation protection garments.

The Maillard reaction in the human body. The main discoveries and factors that affect glycation.

Ever since the discovery of the Maillard reaction in 1912 and the discovery of the interaction between advanced glycation end-products and cellular receptors, impressive progress has been made in the knowledge of nonenzymatic browning of proteins in vivo. This reaction which leads to the accumulation of random damage in extracellular proteins is known to have deleterious effects on biological function, and is associated with aging and complication in chronic diseases. Despite a controlled membrane permeability and a protective regulation of the cells, intracellular proteins are also altered by the Maillard reaction. Two main factors, protein turnover and the concentration of carbonyls, are involved in the rate of formation of the Maillard products. This paper reviews the key milestones of the discovery of the Maillard reaction in vivo, better known as glycation, and the factors which are likely to affect it.

Free glutamine as a major precursor of brown products and fluorophores in Maillard reaction systems.

Glutamine is one of the most abundant free amino acid found in raw food. In this study, the contribution of free glutamine to nonenzymatic browning and fluorescence was investigated using an aqueous model system with methylglyoxal. The results indicated that glutamine contributed to the Maillard reaction via two pathways. First, the hydrolysis of the amide bond of glutamine led to the release of ammonia which was implicated in the formation of brown color and fluorescence. Among other nitrogen donors tested (asparagine, glutamic acid and urea) our results demonstrated that free glutamine was a major source of ammonia during heating. When heated at 120 and 180 degrees C, 100% of ammonia was released from glutamine after 60 and 10 min, respectively. The second pathway involved a direct Maillard reaction with the alpha-amino group of glutamine. Both pathways led to a rapid and complete destruction of glutamine when heated in the model systems. With reference to the Maillard browning (absorbance at 420 nm) glutamine turned out to be the most reactive amine, followed by asparagine, glutamate, ammonia and urea. Maximum fluorescence (excitation and emission wavelengths at 330 and 450 nm, respectively) was also observed with glutamine followed by urea and ammonia. Overall this study suggested that free glutamine predominantly contributes to the color and fluorescence formations of foodstuffs.

Antioxidant vitamins and degenerative pathologies. A review of vitamin C.

In this review we describe how tissues are protected against free radicals and we detail the mechanisms by which the insufficient reduction of ascorbate is involved in glycation and oxidation processes on proteins.

An exactly solvable Ogston model of gel electrophoresis: VIII. Nonconducting gel fibers, curved field lines, and the Nernst-Einstein relation.

In this article, we examine the low-field electrophoretic migration of infinitely small analytes in dilute sieving media made of nonconducting gel fibers. Using an Ogston obstruction model, we show that the electrophoretic mobility is not affected by the presence of curved field lines. In other words, the Nernst-Einstein relation between the mobility and the diffusion coefficient is valid regardless of the electrical properties of the gel fibers. Although this finding may greatly simplify the development of obstruction models of electrophoretic sieving, it also represents a critical test for any analytical or computational approach.

Associations of age, smoking habits and diabetes with plasma vitamin C of elderly of the POLA study.

The objective of this study was to determine the associations of age and sex with plasma vitamin C (vit C) concentration taking into account smoking habits and the presence of age-related pathologies, such as diabetes. The POLA study is a population-based study on age-related eye diseases and their risk factors, and plasma Vitamin C evaluation is part of the biological parameters measured in the 1987 volunteer subjects living in Sète (South of France) and aged more than 60 years. Men had lower average plasma vit C levels than women (31.6 microM.L-1 versus 40.3 microM.L-1, p = 0.001). Plasma vit C was stable as a function of age in women but decreased in men (p = 0.02), enhancing the difference in vit C concentration between men and women with advancing age. Smoking more than 10 cigarettes a day was associated to a lower plasma vit C concentration in men (p = 0.001) but not in women, and diabetic subjects tended to have lower vit C concentrations, the difference being significant only in women (p = 0.003). We conclude that there is a clear influence of sex on plasma vit C. This difference may be due to dietary habits, or metabolism, but may also be due to different sensitivity of age, smoking and to some pathologies.

Risk factors for cortical, nuclear, and posterior subcapsular cataracts: the POLA study. Pathologies Oculaires Liées à l'Age.

The POLA (Pathologies Oculaires Liées à L'Age) Study is a population-based study of cataract and age-related macular degeneration and their risk factors being carried out among 2,584 residents of Sète, southern France, aged 60-95 years. Recruitment took place between June 1995 and July 1997. Cataract classification was based on a standardized lens examination by slit lamp, according to Lens Opacities Classification System III. This paper presents results obtained from cross-sectional analysis of the first phase of the study. In polytomous logistic regression analyses, an increased risk of cataract was found for female sex (cataract surgery: odds ratio (OR) = 3.03; cortical cataract: OR = 1.67), brown irises (cortical, nuclear, and mixed cataracts: OR = 1.61), smoking (cataract surgery: OR = 2.34 for current smokers and OR = 3.75 for former smokers), known diabetes of 10 or more years' duration (posterior subcapsular, cortical, and mixed cataracts and cataract surgery: OR = 2.72), use of oral corticosteroids for at least 5 years (posterior subcapsular cataract: OR = 3.25), asthma or chronic bronchitis (cataract surgery: OR = 2.04), cancer (posterior subcapsular cataract: OR = 1.92), and cardiovascular disease (cortical cataract: OR = 1.96). Decreased risk of cataract was found with higher education (all types of cataract and cataract surgery: OR = 0.59), hypertension (cataract surgery: OR = 0.57), and high plasma retinol levels (nuclear and mixed cataracts and cataract surgery: OR = 0.75 for a 1-standard-deviation increase). Most of the risk factors identified in this study confirm the findings of other studies. The association of cataract with plasma retinol level requires further investigation.

Theory of DNA electrophoresis: a look at some current challenges.

Although electrophoresis is one of the basic methods of the modern molecular biology laboratory, new ideas are being suggested at an accelerated rate, in large part because of the pressing demands of the biomedical community. Although we now have, at least for some methods, a fairly good theoretical understanding of the physical mechanisms that lead to the observed peak spacings, widths and shapes, this knowledge is often too qualitative to be used to guide further technical developments and improvements. In this article, we review some selected elements of the current state of our theoretical ignorance, focusing mostly on DNA electrophoresis, and we offer several suggestions for further theoretical investigations.

Outcome of fetuses diagnosed with atrioventricular septal defect.

OBJECTIVE: To quantify the association of prenatally diagnosed atrioventricular septal defect with Down syndrome and to evaluate its impact on obstetric and neonatal outcomes. METHODS: Charts of 42 cases of atrioventricular septal defect diagnosed by fetal echocardiography from July 1985 to July 1997 were reviewed for prenatal history and outcome data (pregnancy outcome, pathologic confirmation, postnatal echocardiographic findings, and neonatal outcome). Statistical analysis was done using Fisher exact test and odds ratios. RESULTS: The mean gestational age at diagnosis was 26 weeks. Four cases could not be confirmed antenatally on repeat echocardiograms and were excluded. Reasons for referral of the remaining 38 fetuses included an abnormal four-chamber view in 76%. Twenty-two fetuses (58%) had abnormal karyotypes: 19 trisomy 21, one trisomy 18, one trisomy 13, and one mosaicism. The cardiac lesions were isolated in 20 fetuses (53%). After excluding cases of termination, ten of 12 fetuses (83%) with Down syndrome survived, compared with seven of 13 (54%) with normal karyotypes (P = .125). The odds of trisomy 21 were 16 times higher (95% confidence interval 3.0, 85.3) in fetuses with isolated cardiac lesions compared with those with associated cardiac anomalies. CONCLUSION: Prenatal diagnosis of atrioventricular septal defect was associated with a 58% risk of aneuploidy (mainly trisomy 21). Down syndrome fetuses with this cardiac anomaly appeared to have a better survival rate than fetuses with normal karyotypes. Our sample did not have enough power to show a statistically significant difference. When an isolated atrioventricular septal defect was diagnosed prenatally, the odds of trisomy 21 were significantly higher than when other associated cardiac lesions were diagnosed. This information should be considered in prenatal counseling for atrioventricular septal defect.