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The tolerance of a low molecular weight heparin (Fraxiparine, Choay, Paris, France) in normal individuals was determined using a two part investigation. Study 1 consisted of administering escalating doses of Fraxiparine in a single blinded, placebo controlled, rising dose tolerance evaluation. The daily doses tested were 3750 U AXA IC, 7500 U AXa IC, 11250 U AXa IC, 15000 U AXa IC, and 22500 U AXa IC Fraxiparine subcutaneously for 5 consecutive days. In study 2, we compared the tolerance of unfractionated heparin (UH) administered as 5000 IU every 8 hours, to that of 7500 U AXa IC/day or 15000 U AXa IC/day of Fraxiparine administered once daily. Our results indicated very good tolerance to this low molecular weight heparin (LMWH) at doses up to and including 22500 U AXa IC/day. We observed significantly elevated increases in transaminases following LMWH administration. In our second study we observed that the increase in serum transaminases seen after 15000 U AXa IC/day Fraxiparine was without significant difference from that observed following UH (5000 IU every 8 hours). AXa examination revealed an accumulation of AXa effect after 5 days of administration at doses greater than 15000 U AXa IC, and there was good correlation between AXa and APTT at Fraxiparine doses greater than 15000 U AXa IC/day. No thrombocytopenia was associated with Fraxiparine. We conclude that Fraxiparine is relatively well tolerated and shows accumulation after daily dosing with greater than 15000 U AXa IC.

SummarySkin collagen samples from vitamin B2-or B6-deficient rats, weight-matched controls, and control rats fed ad libitum were examined for biomechanical and biophysical properties like tensile strength, shrinkage temperature, gel-reversibility of salt-soluble collagen, and susceptibility of insoluble collagen to denaturing and proteolytic agents.

Riboflavin deficiency and food restriction were associated with greater solubility and lesser total and insoluble collagen concentration in rat skin. Studies using ³H-proline suggest that the lower collagen concentration under these conditions could be due to a decrease in synthesis as well as slow maturation of collagen. The mechanisms underlying defective cross-link formation appear to be different in food-restricted and riboflavin-deficient rats. Half-life of soluble collagen was not affected in riboflavin deficiency, but it was slightly shorter in food-restricted weight-matched animals.

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