Hereditary osteo-onycho-renal dysplasia with excess urinary pyridinoline cross-links and abnormal kidney collagen cross-linking.

HOOD syndrome is a rare genetic disorder also known as nail patella syndrome. Biochemical and molecular biological data are rare and not conclusive. Preliminary data suggest the involvement of collagen type IV. This would, however, not be enough to explain nail or bone involvement. As kidney pathology would be consistent with a cross-linking disorder, we tested collagen IV and kidney collagen cross-linking on SDS-PAGE. This method showed a remarkable reduction in high-molecular-weight collagen polymers. The patient's and his mother's urinary pyridinoline cross-link excretion was manifold increased. Disturbed cross-linking of connective tissue proteins would help to explain the multiorgan involvement.

Oral administration of homocysteine leads to increased plasma triglycerides and homocysteic acid-additional mechanisms in homocysteine induced endothelial damage?

Increased plasma homocyst(e)ine is strongly correlated with occlusive arterial diseases. A series of different hypotheses have been reported including involvement of free oxygen radicals and therefore oxidative stress. We determined plasma homocyst(e)ine and homocysteic acid levels after oral low dose homocysteine thiolactone administration to rats for a period of six weeks. Plasma levels of homocyst(e)ine and triglycerides were significantly elevated in the group fed homocysteine thiolactone. GC/MS determination of ketone body formation showed that the underlying mechanism for the increase of triglycerides seems to be inhibition of fatty acid oxidation. Homocysteic acid was detected in the experimental group exclusively. The present study showing a homocyst(e)ine correlated increase of plasma triglycerides by the inhibition of fatty acid oxidation may well propose an additional role of triglycerides for vascular pathology. The presence of homocysteic acid in the experimental group only would support the free oxygen radical hypothesis for the development of vascular changes but homocysteic acid as a potent neurotransmitter could play an independent role in the pathogenesis.

The effect of ovariectomy of serum amino acids and cholesterol in the rat.

As steroid hormones are known to influence amino acid metabolism we tested the hypothesis that ovariectomy should lead to significant changes in this system.We found that after ovariectomy serum alanine was significantly decreased (p = 0.0006) in contrast to serum glycine and branched chain amino acids (BCAA). The ratio of glycine/BCAA, a parameter for anabolism or catabolism was not changed after ovariectomy. If, however, the amino acid alanine as the link to carbohydrate and lipid metabolism was introduced the alanine/BCAA ratio was significantly altered (p = 0.01).Although serum cholesterol was altered as well (increased,p = 0.03), no significant correlation with alanine was found. We can therefore assume that there are two independent mechanisms for lipid and amino acid changes after ovariectomy.The most prominent finding was that estradiol replacement after ovariectomy restored increased cholesterol levels but did not restore alanine levels. Other ovarial hormones must be incriminated for the regulation of alanine metabolism. The anabolic effects of estradiol as decreasing glycine and BCAA were noticed which rules out insufficient estradiol replacement.

The effect of homocysteine thiolactone and its alpha methylated derivative on bone matrix in the mouse.

Homocysteine (HC) is a radiation protector but toxic to bone. Its derivative homocysteine thiolactone (HCTL) and the alpha-alkylated analogue (A-methyl-HCTL) was fed to mice for a period of six weeks in a daily dose of 50 mg/kg body weight. Parameters for bone matrix as collagen content, acid solubility of bone collagen, urinary bone collagen cross links (pyridinolines) and urinary acid glycosaminoglycans were determined. Urinary acid glycosaminoglycans were significantly reduced in the HCTL treated group but not in the alpha-methyl-homocysteine thiolactone (A-methyl-HCTL) group (controls: 45 ± 7 mg/mmol creatinine, homocysteine thiolactone 38 ± 5 mg/mmol creatinine, A-methyl HCTL 45 ± 6 mg/mmol creatinine).No differences were found for the parameters of bone collagen between the groups. The potent radiation protecting methylated derivative therefore did not change bone matrix and should be a candidate for further toxicological studies.