A story of two transitions: From adhesive to abrasive wear and from ductile to brittle regime.

Atomistic simulations performed with a family of model potential with tunable hardness have proven to be a great tool for advancing the understanding of wear processes at the asperity level. They have been instrumental in finding a critical length scale, which governs the ductile to brittle transition in adhesive wear, and further helped in the understanding of the relation between tangential work and wear rate or how self-affine surfaces emerge in three-body wear. However, so far, the studies were mostly limited to adhesive wear processes where the two surfaces in contact are composed of the same material. Here, we propose to study the transition from adhesive to abrasive wear by introducing a contrast of hardness between the contacting surfaces. Two wear processes emerge: one by gradual accretion of the third body by detachment of chips from both surfaces and the other being a more erratic mixed process involving large deformation of the third body and removal of large pieces from the soft surface. The critical length scale was found to be a good predictor of the ductile to brittle transition between both processes. Furthermore, the wear coefficients and wear ratios of soft and hard surfaces were found to be consistent with experimental observations. The wear particle is composed of many concentric layers, an onion-like structure, resulting from the gradual accretion of matter from both surfaces. The distribution of sizes of these layers was studied, and it appears that the cumulative distribution of hard surface's chip sizes follows a power law.

El pediatra y los padres en la toma de decisiones de tratamiento en plagiocefalia posicional: una revisión narrativa / The pediatrician and parents in treatment decision-making in positional plagiocephaly: A narrative review

La plagiocefalia posicional (PP) es una de las causas más frecuentes de consulta en neurocirugía pediátrica. La incidencia de PP aumentó en los '90, a partir de la campaña Dormir de espaldas. Junto con el aumento de la demanda de atención, se verifica un debate acerca de la eficacia de los distintos tratamientos. La interacción padres ­ pediatra orientada a elegir la mejor terapéutica adquiere importancia, particularmente cuando se trata de decisiones sensibles a la preferencia. Es necesario saber más acerca de la naturaleza de la toma de decisiones de tratamiento de PP, para contribuir al desarrollo de procesos decisorios eficaces. Se realizó una revisión narrativa sobre investigaciones en toma de decisiones de tratamiento en PP. Se identificaron artículos en PubMed y Google Scholar (1990 ­ 2022) en una búsqueda con los descriptores "plagiocephaly", "decision making" y "parents". Se incluyeron artículos cuyo tema central fuera la toma de decisiones en PP, o que la desarrollaran como parte de otro tema. Se excluyeron trabajos en los que la toma de decisiones aparece de modo secundario o tangencial. Se encontraron 3 artículos con distintos diseños metodológicos, en los que la severidad de la presentación, los elementos socioculturales y emocionales, y los aspectos relacionados con el tratamiento son los factores más implicados en la toma de decisiones. Las relaciones entre la ansiedad parental, las expectativas de tratamiento y la percepción subjetiva de la PP, y el rol del pediatra como proveedor de información válida y confiable son temas que necesitan de ulterior investigación (AU)

Positional plagiocephaly (PP) is one of the main reasons for consultation in pediatric neurosurgery. The incidence of PP increased in the 1990s, after the "Back to Sleep" campaign. Concurrently, the growing demand for care has led to a debate regarding the effectiveness of the different treatments. The parent-pediatrician interaction is aimed at choosing the best therapeutic approach becomes important, particularly when it comes to preference-sensitive decisions. There is a need to better understand the nature of PP treatment decision-making in order to contribute to the development of effective decisionmaking processes. In this narrative review, we evaluated the research on treatment decision-making in PP. Articles were identified in PubMed and Google Scholar (1990 - 2022) using the search terms "plagiocephaly", "decision-making" and "parents". Articles were included if their central theme was decision-making in PP, or if they developed it as part of another subject. We excluded articles in which decision-making appeared in a secondary or tangential way. Three articles were identified with different methodological designs, in which the severity of the presentation, sociocultural and emotional aspects, and aspects related to treatment were the factors most implicated in decision making. The relationships between parental anxiety, treatment expectations, subjective perception of PP, and the role of the pediatrician as a provider of valuable and reliable information are topics that require further investigation (AU)

Hippocampal sclerosis induced in mice by a Taenia crassiceps metacestode factor.

An experimental Taenia crassiceps mouse model was used to assess the role of Taenia solium metacestode factor (Fac) in human neurocysticercosis. Intraperitoneal infection with T. crassiceps metacestodes or subcutaneous inoculation with a T. crassiceps metacestode factor (Fac) produced significant impairment of performance (learning) in the Barnes maze and induced bilateral hippocampal sclerosis in mice. Several staining techniques revealed important cell dispersion, extensive apoptosis and cell loss in the dentate gyrus, hilus and CA1-CA3 regions of both hippocampi, as well as intense deterioration of the adjacent cortex. An outstanding disruption of its histoarchitecture in the surrounding tissue of all these regions and apoptosis of the endothelial cells were also observed.

Apoptosis of mouse hippocampal cells induced by Taenia crassiceps metacestode factor.

Seizures, headache, depression and neurological deficits are the signs and symptoms most frequently reported in human neurocysticercosis. However, the cause of the associated learning and memory deficits is unknown. Here, we used Taenia crassiceps infection in mice as a model of human cysticercosis. The effects of T. crassiceps metacestode infection or T. crassiceps metacestode factor (MF) treatment on mouse hippocampal cells were studied; control mice were included. At 45 days after infection or treatment of the mice with MF, all mice were anaesthetized and perfused transcardially with saline followed by phosphate-buffered 10% formalin. Then the brains were carefully removed. Coronal sections stained using several techniques were analysed. Extensive and significant apoptosis was found in the experimental animals, mainly in the dentate gyrus, CA1, CA2, CA3 and neighbouring regions, in comparison with the apparently intact cells from control mice (P < 0.01). These results suggest that neurological deficits, especially the learning and memory deficits, may be generated by extensive apoptosis of hippocampal cells.

A Taenia crassiceps factor induces apoptosis of spleen CD4+T cells and TFG-ß and Foxp3 gene expression in mice.

This study was undertaken to determine whether a parasite substance produces structural pathology in the mouse spleen. A low-molecular-weight Taenia crassiceps metacestode factor (MF) isolated from the peritoneal fluid of female mice infected with T. crassiceps metacestodes induced pathological and immunological changes in mouse spleen cells in vivo. Electron microscopy and confocal microscopy revealed severe changes in the spleen histoarchitecture of T. crassiceps-infected and MF-treated mice. Apoptotic degenerated spleen cells were observed in the white and red pulps and were more conspicuous in the white pulp of the spleen from the T. crassiceps-infected mice than in that of the MF-treated mice. Flow cytometry analysis revealed that the numbers of spleen CD4+T cells were significantly lower in both experimental groups than in control mice. The ex vivo expression of transforming growth factor (TGF)-ß and factor Foxp3 were significantly higher in splenocytes of the experimental mice than the basal expression observed in the control cells. These findings may have potential applications for a better understanding of the host-parasite relationship in human neurocysticercosis.

A Taenia crassiceps metacestode factor enhances ovarian follicle atresia and oocyte degeneration in female mice.

The histopathological effects of Taenia crassiceps infection or T. crassiceps metacestode factor inoculation on the mouse ovary were determined using six female mice in three groups: infected mice, mice inoculated with the metacestode factor and control mice. The control group was subcutaneously inoculated with healthy peritoneal fluid. The infected group was intraperitoneally inoculated with 40 T. crassiceps metacestodes, and the metacestode factor group was subcutaneously inoculated with T. crassiceps metacestode factor (MF). Light and electron microscopy and TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labelling) assays revealed a significant increase in ovarian follicular atresia (predominantly in antral/preovulatory stages of development), oocyte degeneration (P< 0.05), and a decrease in the amount of corpus luteum in follicles of mice infected and inoculated with MF compared with the control group. Significant abnormalities of the granulosa cells and oocytes of the primordial, primary and secondary ovarian follicles occurred in both treated mouse groups (P< 0.05) compared with no degeneration in the control group. These pathological changes in female mice either infected with T. crassiceps metacestodes or inoculated with T. crassiceps MF may have consequences for ovulation and fertility.

Development of an in vitro model of menopause using primary human dermal fibroblasts.

OBJECTIVE: To overcome the current lack of in vitro models to specifically reproduce hormonal skin ageing in women, and in search of active ingredients with innovative efficacy claim for cosmetic skin care, we developed a cell culture-based model by simulating menopause's hormonal decline and assessed several parameters of collagen metabolism. METHODS: Human dermal fibroblasts were incubated with media containing 17ß-oestradiol, progesterone, dehydroepiandrosterone, growth hormone and insulin-like growth factor-1 at concentrations corresponding to those of non-menopausal women's sera and then of menopausal women's sera. We measured cell proliferation [by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)], matrix metalloproteinase-1 and metalloproteinase-3 (MMPs) release (by enzyme-linked immunosorbent assay - ELISA), total collagen deposition (by Sirius red staining), types I and III collagen deposition (by ELISA), and types I and III procollagen gene expression (by real-time q-RT-PCR). RESULTS: Our results showed a significant decrease over time in cell proliferation, collagen deposition and type III/type I collagen ratio, together with an increase in MMP release, when cells were incubated in media containing sex hormones at menopausal levels. This is consistent with in vivo data from menopausal women available in the literature. Surprisingly, procollagen gene expression was only reduced within the first hours and increased afterwards when compared with non-menopausal culture conditions. CONCLUSION: Our results demonstrated that the increased procollagen synthesis with menopausal conditions was not sufficient to compensate for the MMPs' catabolic effects and/or the impaired procollagen protein maturation, resulting in a decrease in extracellular collagen content. These findings add to the overall understanding of hormone-dependent skin behaviour and highlight the suitability of this in vitro model for cosmetic actives testing aiming to underpin claims of anti-ageing efficacy, specifically for menopausal women, regarding collagen metabolism and balance of types, for maintenance of dermal mechanical properties.

Improved procedures for in vitro skin irritation testing of sticky and greasy natural botanicals.

Skin irritation evaluation is an important endpoint for the safety assessment of cosmetic ingredients required by various regulatory authorities for notification and/or import of test substances. The present study was undertaken to investigate possible protocol adaptations of the currently validated in vitro skin irritation test methods based on reconstructed human epidermis (RhE) for the testing of plant extracts and natural botanicals. Due to their specific physico-chemical properties, such as lipophilicity, sticky/buttery-like texture, waxy/creamy foam characteristics, normal washing procedures can lead to an incomplete removal of these materials and/or to mechanical damage to the tissues, resulting in an impaired prediction of the true skin irritation potential of the materials. For this reason different refined washing procedures were evaluated for their ability to ensure appropriate removal of greasy and sticky substances while not altering the normal responses of the validated RhE test method. Amongst the different procedures evaluated, the use of a SDS 0.1% PBS solution to remove the sticky and greasy test material prior to the normal washing procedures was found to be the most suitable adaptation to ensure efficient removal of greasy and sticky in-house controls without affecting the results of the negative control. The predictive capacity of the refined SDS 0.1% washing procedure, was investigated by using twelve oily and viscous compounds having known skin irritation effects supported by raw and/or peer reviewed in vivo data. The normal washing procedure resulted in 8 out of 10 correctly predicted compounds as compared to 9 out of 10 with the refined washing procedures, showing an increase in the predictive ability of the assay. The refined washing procedure allowed to correctly identify all in vivo skin irritant materials showing the same sensitivity as the normal washing procedures, and further increased the specificity of the assay from 5 to 6 correct predictions out of 7 non irritants as compared to the normal washing procedures. In addition, when exposed to non-irritant oily and viscous materials, tissues rinsed with 0.1% SDS generally showed increased viabilities accompanied by decreased variabilities as compared to the normal washing procedures. Similar results were obtained when testing typical in-house natural botanical ingredients. In conclusion, the use of a refined washing procedure making use of SDS 0.1% in PBS was found a suitable procedure to ensure efficient removal of greasy and sticky materials, leading to an increased predictive capacity and decreased variability of the tissue responses while maintaining its sensitivity and not affecting untreated tissues morphology and viability.

Successful micronucleus testing with the EPI/001 3D reconstructed epidermis model: preliminary findings.

Currently, the cosmetics industry relies on the results of in vitro genotoxicity tests to assess the safety of chemicals. Although the cytokinesis-block micronucleus (CBMN) test for the detection of cells that have divided once is routinely used and currently accepted by regulatory agencies, it has some limitations. Reconstituted human epidermis (RHE) is widely used in safety assessments because its physiological properties resemble those of the skin, and because it allows testing of substances such as hydrophobic compounds. Thus, the micronucleus test is being adapted for application in RHE-reconstructed tissues. Here we investigated whether two different reconstructed epidermis models (EPI/001 from Straticell, and RHE/S/17 from Skinethic) are suitable for application of the micronucleus test. We found that acetone does not modify micronucleus frequency, cell viability, and model structure, compared with non-treated RHE. Treatment of the EPI/001 model with mitomycin C and vinblastine resulted in a dose-dependent increase of micronucleus frequency as well as a decrease of tissue viability and of binucleated cell rate, while no changes of the epidermal structure were observed. The number of binucleated cells obtained with the RHE/S/17 model was too small to permit micronucleus testing. These results indicate that the proliferative rate of the tissue used is a critical parameter in performing the micronucleus test on a 3D model.

Receptors and aging: structural selectivity of the rhamnose-receptor on fibroblasts as shown by Ca(2+)-mobilization and gene-expression profiles.

Qualitative and quantitative modifications of receptors were shown to play a key role in cell and tissue aging. We recently described the properties of a rhamnose-recognizing receptor on fibroblasts involved in the mediation of age-dependent functions of these cells. Using Ca(2+)-mobilization and DNA-microarrays we could show in the presence of rhamnose-rich oligo- and polysaccharides (RROPs) Ca(2+)-mobilization and changes in gene regulation. Here, we compared the effects of several RROPs, differing in their carbohydrate sequence and molecular weights, in normal human dermal fibroblasts (NHDFs). It appeared that different structural features were required for maximal effects on Ca(2+)-mobilization and gene-expression profiles. Maximal effect on Ca(2+) influx and intracellular free calcium regulation was exhibited by RROP-1, a 50 kDa average molecular weight polysaccharide, and RROP-3, a 5 kDa average molecular weight oligosaccharide with a different carbohydrate sequence. Maximal effect on gene-expression profiles was obtained with RROP-3. These results suggest the possibility of several different transmission pathways from the rhamnose-receptor to intracellular targets, differentially affecting these two intracellular functions, with potential consequences on aging. Although of only relative specificity, this receptor site exhibits a high affinity for rhamnose, absent from vertebrate glycoconjugates. The rhamnose-receptor might well represent an evolutionary conserved conformation of a prokaryote lectin.

Dynamic fragmentation of a ring: predictable fragment mass distributions.

We employ a finite element framework, coupled to cohesive elements, to model material decohesion of a uniformly expanding ring. Our study focuses on the average fragment mass, the distribution of fragment masses, and the heaviest fragments. The computed fragment mass distributions are best captured by generalized gamma distributions, regardless of the model parameters. However, the distribution of the heaviest fragments depends on toughness, specimen size, and loading rate.

Age- and passage-dependent upregulation of fibroblast elastase-type endopeptidase activity. Role of advanced glycation endproducts, inhibition by fucose- and rhamnose-rich oligosaccharides.

It could be shown using the in vitro cell culture aging model, that elastase-type endopeptidase activity is progressively upregulated with successive passages (in vitro aging). Similar results were obtained previously by determining elastase-type activity as a function of age in aorta extracts (human) and skin extracts (mouse). Among the possible mechanisms involved we tested the role of advanced glycation endproducts (AGEs) on this process. AGE-production was shown to increase with age, exemplified by the exponential age-dependent crosslinking of collagen, demonstrated by Fritz Verzár, already in 1963. Several AGEs significantly upregulated elastase-type activity when added to the culture medium of fibroblasts. This effect appears to be mediated by some AGE-receptors as shown previously, and could be inhibited by a 5 kDa rhamnose-rich oligosaccharide (RROP-3) as well as by a fucose-rich oligosaccharide (FROP-3). When present in the culture media, RROP-3 and FROP-3 efficiently inhibited the passage-dependent upregulation of elastase-type activity expressed by human skin fibroblasts. The use of specific inhibitors and zymography suggested that matrix metalloproteinases (MMP)-9 activation and expression are mainly involved. A detailed discussion is proposed for the interpretation of age-dependent modifications of tissues as vascular wall and skin in the light of these and related experiments, highlighting the role of several specific receptors in the mediation of the observed reactions.

The alpha-L-Rhamnose recognizing lectin site of human dermal fibroblasts functions as a signal transducer: modulation of Ca2+ fluxes and gene expression.

An alpha-l-Rhamnose specific lectin site was described on human skin keratinocytes and fibrobasts. The addition of Rhamnose-rich oligo- and polysaccharides (RROPs) to fibroblasts has been shown to stimulate cell proliferation and increase extracellular matrix biosynthesis, suggesting that this lectin site functions as a "true" receptor transmitting messages to the cell interior. It was confirmed here that addition of the Rhamnose-rich polysaccharide, RROP-1, to normal human dermal fibroblasts (NHDFs) and human endothelial cells produced a dose-dependent stimulation of the calcium-signaling pathway, inducing fast and transient increases in Ca2+ influx and intracellular free Ca2+ level. The Rhamnose-rich oligosaccharide RROP-3 as well as l-Rhamnose alone were also able to trigger similar intracellular free Ca2+ concentration increases in NHDFs. Moreover, the recording of the RROP-1-induced modification of the gene-expression profile in fibroblasts showed that this polysaccharide triggered a down-regulation of the expression of several growth factors, adhesion molecules and extracellular matrix proteins involved in pro-tumoral activity and/or fibrotic processes. These results further support the hypothesis of a receptor function for the Rhamnose-recognizing lectin site in fibroblasts. Anti-fibrotic and anti-tumoral potential of RROP-1 remains to be further explored.

Effect of advanced glycation endproducts on gene expression profiles of human dermal fibroblasts.

The Maillard reaction and its end products, AGE-s (Advanced Glycation End products) are rightly considered as one of the important mechanisms of post-translational tissue modifications with aging. We studied the effect of two AGE-products prepared by the glycation of lysozyme and of BSA, on the expression profile of a large number of genes potentially involved in the above mentioned effects of AGE-s. The two AGE-products were added to human skin fibroblasts and gene expression profiles investigated using microarrays. Among the large number of genes monitored the expression of 16 genes was modified by each AGE-preparations, half of them only by both of them. Out of these 16 genes, 12 were more strongly affected, again not all the same for both preparations. Both of them upregulated MMP and serpin-expression and downregulated some of the collagen-chain coding genes, as well as the cadherin- and fibronectin genes. The BSA-AGE preparation downregulated 10 of the 12 genes strongly affected, only the serpin-1 and MMP-9 genes were upregulated. The lysozyme-AGE preparation upregulated selectively the genes coding for acid phosphatase (ACP), integrin chain alpha5 (ITGA5) and thrombospondin (THBS) which were unaffected by the BSA-AGE preparation. It was shown previously that the lysozyme-AGE strongly increased the rate of proliferation and also cell death, much more than the BSA-AGE preparation. These differences between these two AGE-preparations tested suggest the possibility of different receptor-mediated transmission pathways activated by these two preparations. Most of the gene-expression modifications are in agreement with biological effects of Maillard products, especially interference with normal tissue structure and increased tissue destruction.

Effect of cellular aging on collagen biosynthesis: I. Methodological considerations and pharmacological applications.

The study of the age and passage dependent modifications of collagen biosynthesis requires a simple, rapid and reproducible procedure adaptable to serial cell cultures. To make such a method comparable to other methods of collagen determination, we calibrated a colorimetric procedure both by hydroxyproline (HYP) determinations and in terms of collagen concentration. For collagen types I and IV, widely different slopes were obtained with the colorimetric procedure. To further refine the procedure, we tempted to completely inhibit collagen synthesis by beta-aminopropionitrile (beta APN) added to cultures in order to obtain a negative control. Using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl 2H-tetrazolium bromide (MTT-test), it could be shown that relatively high concentrations of beta APN are tolerated by the cells. It appeared, however, that even the highest concentration of beta APN (1mM) still tolerated by the fibroblasts did not completely inhibit collagen synthesis. At low concentrations, beta APN even stimulated cell-proliferation. The colorimetric procedure calibrated in terms of collagen type I concentration, was therefore retained for the serial determination of collagen synthesis and accumulation. We shall here describe the methodological details of its validation as well as its application for the pharmacological study of the effect of aging on collagen biosynthesis. Among the factors involved, the accumulation of advanced glycation end-products (AGEs) might well play an important role. Several of such AGE-products showed a significant inhibition of collagen deposition. On the contrary, retinol, ascorbic acid as well as the rhamnose-rich oligo- and polysaccharides (RROPs) did produce a significant upregulation collagen deposition. Polysaccharide preparations, rich in rhamnose and fucose (the EROB-mixture) could protect against the AGEs-induced inhibition of collagen accumulation.

[Demonstration of the cytotoxic effect of Advanced Glycation Endproducts (AGE-s)]. / Démonstration de l'effet cytotoxique des produits avancés de la glycation (AGE-s).

Advanced Glycation End-products (AGE-s) were shown to exhibit a number of potentially harmful properties in contact with cells and tissues. As their concentrations increases with age, faster even in hyperglycemic individuals, they are considered important for aging- and age-associated pathologies, especially for athero-arteriosclerosis and type II diabetes. We describe here the methods used for the demonstration of a direct cytotoxicity of several AGE-products when added to human skin fibroblast cultures. This cytotoxicity was still demonstrable when cells, previously cultured with AGE-s, were transferred to new medium without AGE-s. This effect, the remanence of cytotoxicity in absence of AGE-s, suggests a certain degree of inheritance, possibly by epigenetic mechanisms, of the cytotoxic effect of AGE-s, mediated by the AGE-receptors (RAGE-s) and inhibited by free radical-scavengers, such as L-Carnosine, Catalase and Rhamnose-rich oligo- and polysaccharides. Such cytotoxicity can occur not only on the skin but also in other tissues. It appears thus that besides the crosslinking of collagen and other macromolecules, the products of the Maillard reaction can exert their harmful cytotoxic effects directly on the cells.

The Cypress aphids in the South of France.

In the South of France, Cinara (Cupressobium) cupressi, the main Cypress aphid, has been studied during 6 years on a mixed hedgerow in which Cupressus sempervirens and C. arizonica had been planted alternatively. In the area, this monoecious aphid is anholcyclic and heavily attended by ants. Continuous observation of the trees and of the colonies allowed a description of the population dynamics and the characterization of the damages. The two cypress species are regularly attacked, but the aphid appears earlier, remains longer and is more abundant on C. sempervirens, than on C. arizonica. The distribution of the colonies among trees is contagious. Some trees or groups of trees are attacked more frequently and/or present colonies earlier, suggesting that the tight interaction with ants may induce hivernation and early attack in some places.

Multiscale modeling of two-dimensional contacts.

A hybrid simulation method is introduced and used to study two-dimensional single-asperity and multi-asperity contacts both quasistatically and dynamically. The method combines an atomistic treatment of the interfacial region with a finite-element method description of subsurface deformations. The dynamics in the two regions are coupled through displacement boundary conditions applied at the outer edges of an overlap region. The two solutions are followed concurrently but with different time resolution. The method is benchmarked against full atomistic simulations. Accurate results are obtained for contact areas, pressures, and static and dynamic friction forces. The time saving depends on the fraction of the system treated atomistically and is already more than a factor of 20 for the relatively small systems considered here.

Protection by rhamnose-rich polysaccharides against the cytotoxicity of Maillard reaction products.

Previous experiments have shown that AGE-products added to human skin fibroblast cultures increased the number of dead cells floating on top of the culture fluid and took up vital dye [1]. In these experiments, we tested several rhamnose-rich polysaccharides for protection against the cytotoxic effect of AGE-s. Added at relatively low concentrations (between 10 and 100 microg/ml) to the culture medium, several of the tested rhamnose-rich oligo- and polysaccharides (RROP-s) gave a significant protection against AGE-induced cytotoxicity. Their effect on cell proliferation was also tested. The number of cells at saturation density was also shown to be influenced by AGE-products added to the cultures. This effect was also, at least partially, corrected by the rhamnose-rich oligo- and polysaccharides. These substances might therefore be considered as of potential therapeutical interest against hyperglycemia induced cytotoxic effects as in type II-diabetes.

Effect of advanced glycation end-products on cell proliferation and cell death.

The effect of advanced glycation end products (AGE-s) was studied on the proliferation and cell death of human skin fibroblasts in culture. Several AGE-products were prepared from proteins, a peptide and amino acids, using Glucose or Fructose, with or without Fe2+. The AGE preparations increased cell death at the 7th day, after only 72 hours of incubation. Some of these glycation products modified also proliferation. This effect of AGE-s was even maintained without these products in fresh medium for a second period of incubation up to 10 days from the start of the experiment. In order to explore the role of AGE-receptors, especially of AGE-receptor and of growth factor receptors (fibroblast and epidermal growth factors receptors), antibodies to these receptors were added to cell cultures and their effect on both cell death and proliferation were determined as for the AGE-s. These anti-receptor antibodies imitated to some extent the results obtained with AGE-s, producing increase of cell death and proliferation, followed above a certain concentration of antibodies by a decrease and a new increase or plateau. This might correspond to the internalization of the receptors followed by a re-expression on the cell membrane. The role of receptor-mediated Reactive Oxygen Species-production was also explored using scavengers: N-acetyl-cysteine (NAC), L-Carnosine, superoxide dismutase (SOD) and Catalase. Several of these scavengers decreased cell death, suggesting that Reactive Oxygen Species-production is partially involved in the observed phenomena.