Journey in the Polyphenol Research World with Ragai Ibrahim.

Dr. Ragai K. Ibrahim, Professor Emeritus at Concordia University, Montréal, Canada, passed away on the November 19, 2017 at the age of 88 years. Dr. Ibrahim dedicated his entire professional life to polyphenols and spent most of his academic career (1967-1997) at the Department of Biology of Concordia University in Montréal. He has been an active member of the Groupe Polyphénols since the beginning. This paper is a tribute to Dr. Ibrahim from some of his former students. An overview of the evolution of polyphenol research since the late 1950s and the outstanding contribution that Dr. Ibrahim had to this topic is given. The input of Dr. Ibrahim's research to the enzymology and genetics of polyphenol biosynthesis is discussed. Furthermore, the links between Dr. Ibrahim's work and some aspects of modern studies on the health benefits of polyphenols are presented.

Treatment of prosthetic joint infections: validation of a surgical algorithm and proposal of a simplified alternative.

The Del Pozo and Patel (DPP) algorithm permits to identify suitable candidates for debridement and implant retention (DR) in prosthetic joint infections (PJI), but does not include gram-negative bacilli (GNB) as a risk factor of worst outcome. We conducted a retrospective study to validate the DPP algorithm and propose a simplified algorithm including GNB PJI. From 2002 to 2009, 73 PJI underwent surgery; 55% were chosen according to PDD algorithm. Non-adherence increased the risk of treatment failure (HR = 4.2). Performing DR in the presence of GNB PJI and performing DR in a joint prosthesis implanted for >3 months without hematogenous infection were independent risk factors. Our simplified algorithm, based on these 2 criteria, showed comparable performance to the DPP algorithm but increased eligibility for DR by a 2.4 fold.

Application and interpretation of an interferon-gamma release assay: Results of an audit in a Canadian centre.

BACKGROUND: Interferon-gamma release assays (IGRAs) are newly approved for diagnosing latent tuberculosis infection (LTBI). An internal audit was conducted to review the use of a newly implemented IGRA at the Hôpital du Sacré-Coeur de Montréal (Montréal, Québec) to evaluate its concordance with Canadian recommendations and its implication on diagnosis. METHODS: From April 2007 to January 2009, all Quantiferon TB Gold In-Tube (QFT, Cellestis inc, USA) tests performed in at the Hôpital du Sacré-Coeur de Montréal were retrieved. Strategies used to investigate LTBI and clinical interpretation of test results were compared with the local algorithm, which is derived from the current national guidelines. RESULTS: A total of 200 patients tested with QFT were included in the analysis. LTBI investigation and QFT testing were considered to be appropriate in 87.5% and 66.5% of patients, respectively. Overall, 67 QFT tests were performed inappropriately; 25 were performed when a LTBI investigation was not indicated and 42 were performed whe LTBI interpretation was possible with the result of the tuberculin skin test alone. Among the 175 patients investigated appropriately for LTBI, 49 QFT tests (28%) were interpreted incorrectly; 32 patients (at high risk of developing active tuberculosis) had a positive tuberculin skin test and a negative QFT result wrongly interpreted as being negative for LTBI and 13 patients should have undergone further LTBI investigations. CONCLUSION: Globally, the present study revealed that there are discrepancies on how the IGRA was employed and interpreted in a Montreal hospital and that strict compliance to the guidelines could significantly reduce errors in interpretation.

HISTORIQUE: Les tests de libération d'interféron gamma (TLIG) ont récemment été approuvés pour diagnostiquer une infection tuberculeuse latente (ITBL). Une vérification interne a été organisée pour examiner l'utilisation d'un nouveau TLIG à l'Hôpital du Sacré-Cœur de Montréal (Montréal, Québec) ainsi que pour en évaluer la concordance avec les recommandations canadiennes et les conséquences sur le diagnostic. MÉTHODOLOGIE: D'avril 2007 à janvier 2009, les chercheurs ont extrait tous les tests Quantiferon TB Gold In-Tube (QFT) effectués à leur centre. Ils ont comparé les stratégies utilisées pour évaluer l'ITBL et l'interprétation clinique des résultats des tests avec leur algorithme local, dérivé des lignes directrices nationales à jour. RÉSULTATS: Au total, 200 patients ayant subi le test QFT ont participé à l'analyse. L'examen de l'ITBL et le test QFT ont été considérés comme convenables chez 87,5 % et 66,5 % des patients, respectivement. Dans l'ensemble, 67 tests QFT avaient été mal exécutés, soit 25 lorsque l'examen de l'ITBL n'était pas indiqué et 42 lorsqu'il était possible d'interpréter l'ITBL grâce aux seuls résultats du test cutané à la tuberculine. Chez les 175 patients ayant subi des examens convenables de l'ITBL, 49 tests QFT (28 %) avaient été mal interprétés. En effet, 32 patients (très vulnérables à une tuberculose active) présentaient un test cutané à la tuberculine positif et un résultat négatif du test QFT interprété à tort comme négatif à l'ITBL, tandis que 13 patients auraient dû subir des examens plus approfondis de l'ITBL. CONCLUSION: Globalement, la présente étude a révélé des divergences dans l'utilisation du TLIG au centre et établi qu'un respect rigoureux des lignes directrices pourrait réduire considérablement les erreurs d'interprétation.

Inter-related in vitro effects of androgens, fatty acids and oxidative stress in prostate cancer: a mechanistic model supporting prevention strategies.

Oxidation of mitochondrial fatty acids (FA) results in the generation of reactive oxygen species (ROS) which have been postulated to play a key role in the initiation and progression of prostate cancer (PC). We previously reported that androgens increase FA uptake into PC cells. We thus examined if androgens that are known to induce ROS generation regulate FA oxidation in PC cells. The effects of the androgen-depleted medium, R1881 (synthetic androgen) and/or androgen receptor blocker, bicalutamide were examined in the human androgen-responsive but not dependent 22rv1 cells. R1881 supplementation significantly increased mitochondrial FA oxidation ((14)C-radiolabeled FA degradation studies), resulting in increased ROS production. Androgens increased the mRNA levels of carnitine palmitoyltransferase (CPT1), the rate limiting enzyme in the process of mitochondrial FA oxidation. Treatment with R1881 and bicalutamide inhibited these androgen regulated effects. Inhibition of mitochondrial ROS generation by two different inhibitors, rotenone and thenoyltrifluoroacetone, eliminated the androgen-induced ROS generation, to the same level as in cells deprived of androgens or treated with R1881 and bicalutamide. Taken together, androgens increase the mitochondrial oxidation of FA, leading to increased production of ROS that is associated with prostate cell proliferation and mutagenesis. These results therefore support the rationale for PC prevention using 5-alpha reductase inhibitors, dietary restrictions or anti-oxidants, each of which has different inhibitory but complementary effects.

Chromatin techniques for plant cells.

A large number of recent studies have demonstrated that many important aspects of plant development are regulated by heritable changes in gene expression that do not involve changes in DNA sequence. Rather, these regulatory mechanisms involve modifications of chromatin structure that affect the accessibility of target genes to regulatory factors that can control their expression. The central component of chromatin is the nucleosome, containing the highly conserved histone proteins that are known to be subject to a wide range of post-translational modifications, which act as recognition codes for the binding of chromatin-associated factors. In addition to these histone modifications, DNA methylation can also have a dramatic influence on gene expression. To accommodate the burgeoning interest of the plant science community in the epigenetic control of plant development, a series of methods used routinely in our laboratories have been compiled that can facilitate the characterization of putative chromatin-binding factors at the biochemical, molecular and cellular levels.

The photomorphogenesis regulator DET1 binds the amino-terminal tail of histone H2B in a nucleosome context.

Light provides a major source of information from the environment during plant growth and development. Recent results suggest that the key events controlling light-regulated gene expression in plants are translocation of the phytochrome photoreceptors into the nucleus, followed by their binding to transcription factors such as PIF3. Coupled with this, the degradation of positively acting intermediates such as the transcription factor HY5 by COP1 and the COP9 signalosome appears to be an important process whereby photomorphogenesis is repressed in darkness (e.g., ). Genetic analyses in Arabidopsis and tomato have revealed that the nuclear protein DET1 also plays a key role in the repression of photomorphogenesis. However, the function of this protein has remained a mystery. In a series of in vitro experiments, we provide persuasive evidence that DET1 binds to nonacetylated amino-terminal tails of the core histone H2B in the context of the nucleosome. Furthermore, we have utilized FRET (fluorescence resonance energy transfer) imaging with GFP variants to demonstrate this interaction within the nucleus of living plant cells. Given the dramatic photomorphogenic phenotypes of det1 mutants, we propose that chromatin remodeling plays a heretofore unsuspected role in regulating gene expression during photomorphogenesis.