Laurent Antunes

Effects of vitamin B12 and folate deficiencies on DNA methylation and carcinogenesis in rat liver.

Abstract Deficiencies of the major dietary sources of methyl groups, methionine and choline, lead to the formation of liver cancer in rodents. The most widely investigated hypothesis has been that dietary methyl insufficiency results in abnormal DNA methylation. Vitamin B12 and folate also play important roles in DNA methylation since these two coenzymes are required for the synthesis of methionine and S-adenosyl methionine, the common methyl donor required for the maintenance of methylation patterns in DNA. The aim of this study was to review the effects of methyl-deficient diets on DNA methylation and liver carcinogenesis in rats, and to evaluate the role of vitamin B12 status in defining carcinogenicity of a methyl-deficient diet. Several studies have shown that a methyl-deficient diet influences global DNA methylation. Evidence from in vivo studies has not clearly established a link between vitamin B12 and DNA methylation. We reported that vitamin B12 and low methionine synthase activity were the two determinants of DNA hypomethylation. Choline- or choline/methionine-deficient diets have been shown to cause hepatocellular carcinoma in 20–50% of animals after 12–24 months. In contrast, the effect of vitamin B12 withdrawal, in addition to choline, methionine and folate, induced hepatocellular carcinoma in less than 5% of

Short-term heart retention and distribution of intramyocardial delivered mesenchymal cells within necrotic or intact myocardium.

Cell therapy with bone marrow mesenchymal stem cells (BMSCs) is a new strategy for treating ischemic heart failure, but data concerning the distribution and retention of transplanted cells remain poor. We investigated the short-term myocardial retention of BMSCs when these cells are directly injected within necrotic or intact myocardium. 111Indium-oxine-labeled autologous BMSCs were injected within either 1-month-old infarction (n = 6) or normal myocardium (n = 6) from rats. Serial in vivo pinhole scintigraphy was scheduled during 1 week in order to track the implanted cells. The myocardial retention of BMSCs was definitely higher in myocardial infarction than in normal myocardial area (estimated percent retention at 2 h: 63 ± 3% vs. 25 ± 4%, p < 0.001) and the estimated cardiac retention values were unchanged in both groups along the 7 days of follow-up. On heart sections at day 7, labeled BMSCs were still around the injection site and appeared confined to the scarred tissue corresponding either to the infarct area or to the myocardium damaged by needle insertion. BMSCs have a higher retention when they are injected in necrotic than in normal myocardial areas and these cells appear to stay around the injection site for at least a 7-day period.

Vitamin B12 Is a Strong Determinant of Low Methionine Synthase Activity and DNA Hypomethylation in Gastrectomized Rats

Background/Aims: The respective influence of folate and vitamin B12 deficiency on MTR activity and transcription, and on DNA methylation is not clearly established. The aim of this study was to assess the respective influence of folate and vitamin B12 deficiency on MTR transcription and activity, and on DNA methylation. Methods: Sixty-one rats were administered normal diet or diet deficient in choline, methionine, folic acid and vitamin B12. Forty-seven of them underwent total gastrectomy or ileal resection. Results: Low vitamin B12 was observed only in gastrectomized rats. Low folate was observed in rats under deficient diet. Total MTR activity (holo- + apoenzyme) was lowered only with vitamin B12 level <200 pmol/l (p = 0.0002), while the ratios of total vs. holo-MTR activity and of transcripts MTR vs. GAPDH (RT-PCR) were unchanged. Vitamin B12 was the single determinant of low MTR (lower quartile, odds ratio = 15.75, p = 0.0017). Low MTR and low vitamin B12 were the two determinants of DNA hypomethylation (lower quartile) (odds ratio = 17.07, p = 0.0006, and odds ratio = 7.31, p = 0.006, respectively). Conclusion: Vitamin B12 affects MTR expression by a non-transcriptional mechanism different from a protective effect on MTR proteolysis. It is also a strong determinant of DNA hypomethylation.

Les conséquences moléculaires de la fixation et de l’inclusion: exemple des acides nucléiques et des protéines

Resume L’utilite scientifique des donnees moleculaires obtenues a partir d’echantillons tissulaires depend directement de la qualite de ces derniers. L’echantillon ideal est une representation complete et non modifiee de la realite tissulaire in vivo . Le but de cette revue est de resumer les effets de la fixation et de l’inclusion sur le contenu et l’integrite des acides nucleiques et des proteines.

Ovarian strumal carcinoid tumor responsible for carcinoid heart disease

We report a case of right ovarian strumal carcinoid tumor responsible for tricuspid regurgitation. Valve replacement and salpingo-oophorectomy were performed. Serotonin level and tomodensitometry were normal at 3-year follow-up. Rarity of strumal carcinoid tumor explains why this tumor has never been reported with carcinoid heart disease before.

Changes in first-pass interstitial kinetics of DTPA in myocardium submitted to low-flow ischemia.

Objectives:This study aimed to determine the changes during ischemia in the myocardial first-pass kinetics of DTPA, an extracellular tracer that is currently used for assessing myocardial perfusion with magnetic resonance imaging (Magnevist). Materials and Methods:Using an indicator-dilution technique, first-pass kinetics of DTPA were compared between normoxia (n = 11) and low-flow ischemia (n = 11) in isolated rabbit hearts perfused with red blood cell-enhanced perfusate. Results:There was no difference between ischemia and normoxia in the interstitial extraction and clearance rates of DTPA. Interstitial distribution volume of DTPA was, however, lower in ischemia than in normoxia (in percent of myocardial volume: 15 ± 11% vs 25 ± 11%, P = 0.02) as a result of a relationship with coronary flow (P < 0.001). Conclusions:During low-flow myocardial ischemia, DTPA kinetics are unchanged, except for the interstitial distribution volume that is decreased, presumably because of the shrinkage of extracellular fluid. These kinetic properties are favorable for detecting myocardial ischemia at rest with magnetic resonance imaging.