[Evaluation of coagulopathies and fibrinolytic abnormalities in central retinal vein occlusion in patients under 60 years of age]. / Apport du bilan des anomalies de la coagulation et de la fibrinolyse dans les occlusions de la veine centrale de la rétine chez les sujets de moins de 60ans.

PURPOSE: To investigate the association of thrombophilic and fibrinolytic factors with central retinal vein occlusion (CRVO) in patients under 60 years of age. MATERIALS AND METHODS: A prospective, observational study of 21 patients with CRVO compared with an age- and sex-matched control group of 23 volunteers was performed. All participants were tested for: cholesterol, hypertension, factors VIII, IX, and XI, homocysteine, antiphospholipid antibodies, antithrombin III, proteins C and S, protein Z and protein Z antibodies, resistance to activated protein C, factor V Leiden mutation, prothrombin mutation, MTHFR genotypes, plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) polymorphisms. RESULTS: There was a significantly higher rate of hyperhomocysteinemia (23.8% versus 0%, P=0.018) in CRVO patients. Increased level of factor VIII was more common in the CRVO group at diagnosis (23.8% versus 0%, P=0.018) but no significant difference was observed after one month (P=0.1). Hypercholesterolemia was more common in the CRVO group (42.8% versus 17.4%, P=0.09). Thirty-eight percent of patients with CRVO were hypertensive. Frequencies of other hypercoagulable states were rare. No significant differences were observed for hereditary fibrinolytic abnormalities. DISCUSSION AND CONCLUSION: Among the coagulopathies studied, hyperhomocysteinemia appears to be a risk factor for central retinal vein occlusion in patients under 60 years of age. Conversely, polymorphisms of fibrinolytic factors do not appear to play a role in this population.

Perinatal folate supply: relevance in health outcome parameters.

The importance of physiological supply of folate is well recognized in human health; the crucial roles of folate in one-carbon metabolism for physiological DNA synthesis and cell division, as well as in the conversion of homocysteine (Hcy) to methionine, and subsequently, to S-adenosylmethionine, have been convincingly demonstrated. Improved folate status may reduce the risk of macrocytic anaemia, cardiovascular diseases, neuropsychiatric disorders and adverse pregnancy outcomes. Inadequate folate status results in a decrease in the methylation cycle and in increased blood levels of the neurotoxic Hcy. The aim of this review is to provide insight into the influence of folate status on pregnancy health outcomes, and to consider increasing evidence of a link between the extent of genome/epigenome damage and elevated risk for adverse obstetrical endpoints. Pregnant women are at risk for folate insufficiency because of the increased need for folate for rapid fetal growth, placental development and enlargement of the uterus. Inadequate folate status may cause fetal malformations, impaired fetal growth, pre-term delivery and maternal anaemia. Even some diseases of the placenta may arise from folate deficiencies. Fetal growth seems to be vulnerable to maternal folate status during the periconception period, because it has the potential to affect both the closure of the neural tube and several epigenetic mechanisms within the placenta and the fetus. Mainly on the basis of the well recognized link between maternal folate status and fetal neural tube defects, women are advised to receive folic acid supplement during the periconceptional period. Because an adequate folate supply seems to play an important role in the implantation and development of the placenta and in improving endothelial function, folic acid supplementation in the late first trimester or early second trimester might also be beneficial.

Molecular mechanisms of homocysteine toxicity.

Hyperhomocysteinemia is a risk factor for a number of cardiovascular and neurodegenerative processes as well as a complicating factor in normal pregnancy. Toxic effects of homocysteine and the product of its spontaneous oxidation, homocysteic acid, are based on their ability to activate NMDA receptors, increasing intracellular levels of ionized calcium and reactive oxygen species. Even a short-term exposure of cells to homocysteic acid at concentrations characteristic of hyperhomocysteinemia induces their apoptotic transformation. The discovery of NMDA receptors both in neuronal tissue and in several other tissues and organs (including immunocompetent cells) makes them a target for toxic action of homocysteine. The neuropeptide carnosine was found to protect the organism from homocysteine toxicity. Treatment of pregnant rats with carnosine under conditions of alimentary hyperhomocysteinemia increases viability and functional activity of their progeny.