Hyperhomocysteinemia (HHcy) has been associated with cognitive impairment in various neurological diseases. Cognitive impairment occurs early in multiple sclerosis (MS). Conflicting data have been reported regarding plasma total homocysteine (tHcy) levels in MS patients, and the impact of HHcy on cognitive impairment in MS is not known. This study investigated whether plasma total homocysteine levels are increased in MS and if HHcy is associated with cognitive impairment in MS. We compared tHcy levels in 94 patients with MS and 53 healthy age-matched controls. We used a neuropsychological test battery that included the Raven's Coloured Progressive Matrices, the Visual Search Test, the Trail Making Test A and B, the Immediate and Delayed Recall of a Short Story, the 30 Paired Word Associates, the Rey-Osterrieth Complex Figure Test, and the Semantic and Verbal Fluency Tests. Clinical (sex, age, type of MS, relapse, disease duration, coexisting disease, smoking habit, and physical disability) and laboratory variables (HHcy, low serum levels of folate and vit.B12, MTHFR genotype) were evaluated for their ability to predict cognitive impairment. The mean tHcy was higher in patients (13.19 micromol/L, SD5.58) than in controls (9.81 micromol/L, SD2.53; p < 0.001). Univariate analysis determined the following factors to be associated with cognitive impairment: higher age at observation, chronic progressive course of disease, longer disease duration,moderate or severe physical disability, and frequency of HHcy. With multivariate regression analysis, there remained a significant association only between frequency of HHcy and cognitive impairment (beta 0.262, p = 0.01). We conclude that tHcy levels are increased in MS and that HHcy is associated with cognitive impairment in this disease.

In this study we have used two new monoclonal antibodies, designated LIP5 and LJP9, as well as a previously described one, AP2, all specific for the platelet membrane glycoprotein (GP)IIb/ IIIa complex. None of them reacted with dissociated GPIIb or GPIIIa. The monovalent Fab fragment of both LJP5 and LJP9 bound to unstimulated platelets in a saturable manner, but binding was markedly decreased after platelets had been incubated at 370C in the absence of added extracellular calcium. The binding of LJP9 was not affected by AP2, but was blocked by excess UP5. On the contrary, the binding of LJP5 was blocked in the presence of both AP2 and LJP9. Thus, these antibodies bound to distinct epitopes of GPIIb/IIIa. At saturation, the binding to unstimulated platelets was between 2.41 and 10.9 X 104 molecules/platelet for LJP5 and between 3.47 and 9.1 X 104 molecules/platelet for LJP9 (range of 11 and 10 experiments, respectively). Binding increased up to 50% after thrombin stimulation. The estimated association constant, K., was 2.7 X 107 M-1 for LJP5 and 3.85 X 107 M-1 for LJP9. Both UP5 and 1JP9 partially inhibited the association of 45Ca2W with the surface of unstimulated platelets. Moreover, both antibodies blocked the binding of von Willebrand factor (vWF) to stimulated platelets, whereas only UJP9, but not UP5, blocked fibrinogen binding. LJP9 was also a potent inhibitor of platelet aggregation, whereas UP5 was without effect in this regard. The results of the present study demonstrate that independent modulation of vWF and fibrinogen binding to stimulated platelets can be attained with monoclonal antibodies directed against distinct epitopes of GPIIb/IIIa.

Elevated plasma homocysteine (Hcy) level is considered a risk factor for vascular diseases. In recent years, many scientific reports have suggested that hyperhomocystinemia may be associated with an increased risk of retinal vascular occlusive disease (RVOD). The prevalence of elevation of homocysteine in patients with a recent retinal vascular occlusion was compared to a health control group in this study. Forty-nine consecutive patients (22 M; 27 F) (age 26-85 years, mean 69) with diagnosis of retinal vascular occlusion were compared with 71 healthy controls. These patients underwent laboratory evaluation for plasma fasting total homocysteine, activated protein C resistance, protein C, protein S, antithrombin III, and antiphospholipid and anticardiolipin antibodies. The G20210 prothrombin gene mutation (FII G20210A) and Factor V Leiden mutation (FVL) were evaluated. None of these enrolled subjects had other prothrombic risk factors. The health control group consisted of healthy subjects from the general population, with no history or clinical evidence of retinal vascular disease, recruited during the same 2-year period. High fasting homocystinemia (higher than 15 mumol/L) was detected in 24/49 subjects (48.9%) (P < .0005). There was a high prevalence of hyperhomocystinemia: these data suggest an association between RVOD and high fasting homocystinemia. Elevated homocysteine may be an independent risk factor, and its assessment may be important in the investigation, management, and follow-up of patients with RVOD. Further controlled studies are necessary to clarify the exact role of hyperhomocystinemia in RVOD and to evaluate the appropriate therapeutic approach.

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our study suggests that HHcy is a possible risk factor for RVT development, while no association was found between RVT and the C677T MTHFR genotype.