Increased urinary excretion of pyridinoline and deoxypyridinoline in a girl with congenital contractural arachnodactyly.

Congenital contractural arachnodactyly (CCA) is caused by mutations in the gene for fibrillin 2 glycoprotein, a component of connective tissue. The causes of osteodystrophy or osteodysplasia in CCA are unknown. We report bone metabolism in a 28 month-old girl with CCA. Serum alkaline phosphatase and osteocalcin levels were 650 IU/l and 22 ng/ml at 1.5 months old (control: 530+/-65, 16.5+/-4.3), and 580 IU/l and 21 ng/ml at 28 months old (control: 465+/-58, 15.0+/-3.5), i.e. in upper-normal levels. The urinary pyridinoline and deoxypyridinoline levels were 1176 and 194 micromol/mol creatinine at 1.5 months old (control: 329+/-76, 63+/-12), and 407 and 111 micromol/mol cr at 28 months old (control: 231+/-49, 50+/-11), apparently higher than the control values. These findings may indicate that abnormal fibrillin may impair bone metabolism and cause the osteodystrophy or osteodysplasia in CCA.

[Excretion of pyridinoline with urine in children with Ehlers-Danlos syndrome and Marfan's syndrome and the effect of beta blocker and complex vitamin therapy on it]. / Ekskretsiia piridinolina s mochoi u detei s sindromami Elersa-Danlo i Marfana i vliianie na nee terapii beta-adrenoblokatorom i kompleksom vitaminov.

Excretion of pyridinoline and polypeptide-bound hydroxyproline with urine was studied in 27 children with hereditary impairment of connective tissue. At the same time, effects of beta-adrenoblocking agents and vitamin complex, prescribed during preoperation period before thoracoplasty in hereditary chest deformation, were investigated. Clinical efficiency of the treatment depended distinctly on the initial value of ratios pyridinoline/creatinine and polypeptide-bound hydroxyproline/creatinine. Total positive effect of the therapeutic course, considering also echocardiographic examination and postoperational complications, was observed in 44% of patients with Ehlers-Dunlop syndrome and in 75% of patients with Marfan syndrome.

[The determination of hydroxyproline in daily urine]. / Opredelenie oksiprolina v sutochnoi moche.

Daily urine hydroxyproline was measured using Stegemann's modified technique. The modified procedure makes use of some elements of the technique developed by Firschein et al. (hydrolysis, filtration, and neutralization of filtrate). The suggested modification is highly sensitive and well reproducible.

Urinary excretion of connective tissue protein markers in arterial disease.

In diseases of major arteries there is an increased turnover of connective tissue components. This implies a greater excretion of fragments of collagen and elastin. The changes for each of these may be useful in further delineating the nature of the disease. In a preliminary study, the urine of 10 Marfan's syndrome patients was analyzed. The hydroxyproline (collagen) concentration was up to eight times higher than that of control subjects. The desmosine (elastin) crosslink concentration was either normal or slightly reduced in these patients. The mean of the ratio of hydroxyproline to desmosine was nearly seven times higher in the patients.

[Effect of therapy with beta-adrenoblockers and vitamin complexes on indices of oxyproline excretion in various hereditary connective tissue diseases]. / Vliianie terapii beta-adrenoblokatorom i kompleksom vitaminov na pokazateli ékskretsii oksiprolina pri nekotorykh nasledstvennykh bolezniakh soedinitel'noi tkani.

Excretion of hydroxyproline with urine was studied in 16 children (5-14 years old) with Marphan-Like syndrome and Marphan, Ehlers-Dunlos and Larson syndromes after therapy involving propranolol and a complex of vitamins (ascorbic acid, riboflavin and pyridoxine) and recommended on the basis of echocardiographic analyses. The therapeutic course appears to cause quantitative and qualitative correction of collagen and apparently of elastin fibrilles development. Depending on initial patterns of hydroxyproline excretion and the syndrome form the correction could be complete or partial, while positive effect of the treatment was stable or provisional. The data obtained suggest that the complex treatment developed might be applied as a preoperative therapy of the patients with Marphan-like syndrome as well as with syndromes of Marphan and Ehlers-Dunlos before thoracoplastics caused by hereditary chest deformation and by impairments of cardiovascular system.

[Urinary excretion of hydroxyproline in funnel chest deformity]. / Ekskretsiia oksiprolina s mochoi pri voronkoobraznoi deformatsii grudnoi kletki.

Excretion of hydroxyproline with urine was studied in 16 children with localized form of funnel chest deformation simultaneously with Marfan and Ehlers-Danlos syndromes, in 9 children with the localized form of deformation within 6-8 months after thorax surgical plastic operation as well as in 3 children with Ehlers-Danlos syndrome but without funnel chest deformation. Funnel chest deformation of the II-III degree, independently of its form, was accompanied by a decrease of total hydroxyproline in urine as compared with healthy children of the similar age. The hydroxyproline excretion was normalized after thoracoplastic operation in the children with localized form of the chest deformation. In Ehlers-Danlos syndrome, independently on presence or absence of the chest deformation, relative content of free hydroxyproline was increased in urine, while the peptide-bound amino acid was decreased (peptides with molecular mass above 700 daltons); this phenomenon appears to be a characteristic property of the syndrome.

Desmosines in human urine. Amounts in early development and in Marfan's syndrome.

Desmosines from 24 h human urine samples were isolated, characterized and quantified. The desmosines are in peptidyl form (1000--1500 molecular weight), and their amount is decreased by two-thirds between 7 and 25 years of age. Patients with Marfan's syndrome have significantly lower urinary amounts of desmosines than do comparable controls during the early development period.

Variations in human urinary O-hydroxylysyl glycoside levels and their relationship to collagen metabolism.

Two O-hydroxylysyl glycosides, Hyl-Gal-Glc and Hyl-Gal, have been isolated from normal human urine and shown to be identical to two glycosides isolated from alkaline hydrolysates of collagen. A relatively sample and reproducible analytical procedure has been devised to measure the levels of these glycosides in human urine. By the use of this procedure it was shown that a normal diet has only a small effect on 24-hr urinary excretion levels of these glycosides indicating an endogenous origin. Urinary glycoside levels appear to be highest in children, roughly paralleling collagen turnover as indicated by urinary hydroxyproline levels. Collagen turnover equivalents calculated from urinary hydroxylysyl glycoside levels were found to be significantly larger than collagen turnover equivalents calculated from urinary hydroxyproline levels. This suggests that urinary glycosides are more quantitative indicators of collagen metabolism than urinary hydroxyproline. The ratio of Hyl-Gal-Glc to Hyl-Gal was measured in urines of diseased as well as normal individuals and a bimodal distribution was found. Alkaline hydrolysates of different human connective tissue collagens showed that only bone collagen, of the collagens examined, had a low ratio of Hyl-Gal-Glc to Hyl-Gal compared to human urine. Other collagens examined had higher ratios than found in human urine. On the basis of these results it is postulated that the bimodal distribution of glycoside ratios represents two populations of collagen turnover, the lower ratio population having a high bone collagen turnover, the lower ratio population having a high bone collagen turnover relative to the second population. Examination of the types of subjects making up the two populations supports this hypothesis. These data suggest that urinary O-hydroxylysyl glycoside excretion, in addition to providing a more quantitative estimate of collagen turnover than urinary hydroxyproline, may prove to be of value as a specific means of studying the metabolism of bone collagen.