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Later, in the 1980s, the development of high-pressure liquid chromatography methods allowed for rapid determination of homocysteine concentrations in 1000s of samples, thus paving the way for epidemiological studies that revealed significant associations between relatively small elevations of homocysteine in blood and cardiovascular, cerebrovascular, and peripheral vascular diseases (7, 46)

were the first to describe increased whole gut permeability in patients with alcohol abuse without significant liver disease, measured by a 24 h urinary excretion of 51 Cr-EDTA, which was confirmed by increased uptake of macromolecules (inulin, EDTA and cyanocobalamin) ex vivo in jejunal biopsies (145)

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