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Le Touquet – Paris-Plage, France

Robert L.,Laboratoire Of Recherche Ophtalmologique
Pathologie Biologie

Serum haptoglobin (Hp) was discovered by Max Fernand Jayle as a young assistant professor in the Department of Biochemistry of the Paris Medical Faculty, headed by Professor Michel Polonovski. Jayle showed that Hp was an acute phase glycoprotein and worked out its routine determination in the blood-serum, based on its complex formation with hemoglobin, using the increased peroxidase activity of the hemoglobin-haptoglobin (Hb-Hp) complex, for routine determination in clinical biochemistry for the characterisation of inflammatory processes, together with other acute phase glycoproteins as orosomucoide. Later Smithies described the genetic control of human Hp-isoforms and quite recently Andersen et al. reported the elucidation of the crystal structure of the porcine Hb-Hp complex. In that article there was no mention of the discovery of Hp, neither of its determination in clinical biochemistry as an inflammatory marker. The only biologically significant role assigned to Hp by Andersen et al. is its (hypothetical) role to prevent or minimize the harmful effects of Hb during intravascular hemolysis, by the generation of reactive oxygen species (ROS) and complexing it. This shift of paradigm, not at all exceptional in medical biochemistry, will be described and discussed with its pitfalls and consequences. © 2013 Elsevier Masson SAS. Source

Bourges J.L.,Center dOphtalmologie | Bourges J.L.,Paris-Sorbonne University | Robert A.M.,Paris-Sorbonne University | Robert A.M.,Laboratoire Of Recherche Ophtalmologique | And 2 more authors.
Pathologie Biologie

Oriented collagen biosynthesis is one of the major mechanisms involved in tissue and organ formation during development. Corneal biogenesis is one example. Defects in this process lead to anomalies in tissue structure and function. The transparency of cornea and its achievement are a good example as well as its pathological modifications. Keratoconus is one example of this type of pathologies, involving also inappropriate cross-linking of collagen fibers. Among the tentatives to correct this anomaly, the riboflavin-potentiated UV-cross-linking (CXL) of keratoconus corneas appears clinically satisfactory, although none of the experiments and clinical results published prove effective cross-linking. The published results are reviewed in this article. © 2014 Published by Elsevier Masson SAS. Source

Robert A.M.,Laboratoire Of Recherche Ophtalmologique | Robert L.,Laboratoire Of Recherche Ophtalmologique | Robert L.,University Paris Diderot
Pathology and Oncology Research

Free radical mediated pathologies occupy a special place in medical semiology and in mechanistic interpretation of diseases. Free radicals, or better reactive oxygen species (ROS) or reactive nitrogen species (RNS) play also an important role in cell signaling. This is the basis of the ambivalent (Jekyll - Hyde) situation of ROS in biology and pathology. Aging itself is attributed by a popular theory to free radicals. A number of ROS - scavenging substances and procedures were described without however reaching credibility for their therapeutic value. An interesting exception is the xanthine oxido - reductase produced ROS and their role in cardiovascular disease. Allopurinol inhibition of xanthine oxido - reductase was shown to be efficient in some cases of cardiovascular diseases. Another important aspect of xanthine oxido - reductase produced ROS is their antibacterial capacity considered to be of importance with newborns fed on milk rich in this enzyme as well as at the gastrointestinal barrier. This ambivalent role of xanthine oxido - reductase justifies this review on the basic enzymatic mechanisms involved, derived ROS production, their role in the abovementioned biological processes and especially the interest of the inhibition of this enzyme as a preventive or curative measure in some cardiovascular pathologies. © Arányi Lajos Foundation 2013. Source

Robert L.,Paris-Sorbonne University | Labat-Robert J.,Laboratoire Of Recherche Ophtalmologique

Longevity is different for every animal species as well as their genome, suggesting a correlation between genes and life-span. Estimates put the genetic effect from 5 to 35 % approximately, suggesting that even genetic effects are dependent on environmental conditions. This contention is largely confirmed by the study of identical twins raised apart. They do not die at the same age and also for different reasons. Aging is not “genetically programmed”, it is outside evolutionary constraint. Evolution favors early and efficient reproduction, but does not care for longevity. A number of mechanisms were shown to be involved in the age-dependent decline of vital functions, among them the Maillard reaction (non-enzymatic glycosylation) and the age-dependent upregulation of proteolytic activity. Aging of ECM is a complex process, comprising progressive modification of its macromolecular components and of cell-matrix interactions. An important process is the uncoupling with age of the elastin-receptor from its “young” transmission pathway loosing all physiological effects, but enhancing free radical and elastase release. These processes contribute to age-related ECM degradation, production of matrikins (ECM degradation products with biological activity) aggravating functional loss with age. Both genetic and post-genetic mechanisms are susceptible to be influenced by medical, pharmacological and dietary interventions. Among the genetic mechanisms, those attributed to Sirtuins (7 orthologs identified in the human genome) are especially important. Among the environmental effects, nutrition, hygiene and weather conditions play a role. These data justify some predictions on the evolution of life expectancy taking in account also socio-economic factors. Biological constraints become evident by the comparison of centenarians and supercentenarians (less than 1 % of the centenarians) putting an upper limit to the attainable human lifespan. © 2014, Springer Science+Business Media Dordrecht. Source

Robert L.,Laboratoire Of Recherche Ophtalmologique | Labat-Robert J.,Laboratoire Of Recherche Ophtalmologique | Robert A.-M.,Laboratoire Of Recherche Ophtalmologique
Pathologie Biologie

The questions we were asked by Dr Edeas, president of the French Society of Antioxydants to discuss in this introductory lecture are the following: (a) the metabolism of glycation; (b) what are its consequences at the cellular level, and (c) their effect on health. As a recent and vast literature is available on these subjects, in the following we present a short survey of some basic data on the proposed subjects, insisting on our own experiments on the cytotoxicity of Maillard products and on a new approach to prevent the aggravation and acceleration of age-related diseases, essentially diabetes type II and its consequences on the cardiovascular system. © 2009 Elsevier Masson SAS. Source

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