[Acute psycho-organic syndrome (author's transl)].
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Biomedical subjects
Publications and source records attributed to R Askenasi.
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Intraperitoneal injection of bovine albumin in rats readily induces proteinuria. It is already known that this proteinuria is accompanied by ultrastructural and enzyme changes in the glomeruli. The purpose of the present study is to investigate whether these phenomena were associated with an increased glomerular protein synthesis or, more specifically, with an increased glomerular basement membrane (GBM) synthesis. Young rats were made proteinuric by the injection of bovine albumin. Their glomeruli were isolated by the sieve technique and incubater either with [U-14C]proline or with [U-14C]leucine and [U-14C]tyrosine. Control incubations were run with normal glomeruli. Glomerular proteins were hydrolyzed and analyzed for amino acid composition and radioactivity. Specific activities of all three amino acids were always higher in proteinuric glomeruli, but there was no difference in the ratio 14C-hydroxyproline/14C-proline. The similar increase in incorporation of the three amino acids must result from an increased synthesis of different cellular proteins and cannot be considered as a preferential increase in GBM synthesis.
The urinary excretion of glucosyl-galactosyl-hydroxylysine and of galactosyl-hydroxylysine were studied in Paget's disease of bone and in primary hyperparathyroidism. Both metabolites were increased in these diseases. Although glucosyl-galactosyl-hydroxylysine is not abundant in bone collagen, it is possible that a part of it originates from calcified tissue.
About 10% of the urinary hydroxylysine is linked to peptides. There is no significant difference between the excretion of peptide-bound hydroxylysine and hydroxylysine measured in the non-dialysable fraction of the urine. Non-dialysable hydroxylysine is highly glycosylated and contains mainly glucosyl-galactosyl-hydroxylysine. It is concluded that the urinary peptide-bound hydroxylysine is present in the non-dialysable collagen polypeptides. Their unusual carbohydrate composition is discussed.
1. Subcutaneous inflammatory granuloma were induced in young rats and the urinary excretion of hydroxyproline and hydroxylysyl glycosides was observed during the period of acute inflammation. 2. All collagen metabolites were increased in the urine and excretion of glucosyl-galactosyl-hydroxylysine was much greater than excretion of galactosyl-hydroxylysine in the first days. 3. It is argued that urinary glucosyl-galactosyl-hydroxylysine is probably derived from hydroxylysyl residues of soluble collagen. 4. This study affords new arguments in favour of the dermal origin of urinary glucosyl-galactosyl-hydroxylysine, at least in skin inflammation.
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The amount of urinary hydroxylysine is an index of collagen metabolism. Of the total hydroxylysine measured in normal urine 80 percent is associated with sugars in two glycosidic compounds, glucosyl-galactosyl-hydroxylysine and galactosyl-hydroxylysine, ten percent is free and unglycosylated and the remainder is bound to urinary peptides. The excretion of hydroxylysyl glycosides follow the same physiological variations as urinary hydroxyproline, but it is not influenced by a collagen-free diet. The urinary excretion of hydroxylysyl glycosides, free hydroxylysine and peptide-bound hydroxylysine increases from 6 months of age to puberty. When corrected for urinary creatinine excretion, the largest amounts are found before one year of age. The glucosyl-galactosyl-hydroxylysine/galactosyl-hydroxylysine ratio is lower in the urine of children. After correction of the values to either the body surface area or to the creatinine excretion, no significant differences can be found between the sexes. The different forms of hydroxylysine are discussed.
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Urinary excretion of hydroxylysyl glycosides, two specific collagen metabolites, was measured in 18 patients with hyperthyroidism and 4 patients with hypothyroidism. As in the case of hydroxyproline, values were high in thyrotoxicosis and low in hypothyroidism. The glucosyl-galactosyl-hydroxylysine/galactosyl-hydroxylysine urinary ratio which indicates the bone or skin origin of degraded collagen was found to be unchanged in hyperthyroidism, except in two cases complicated with hypercalcemia where it was very low. This finding provides a further argument in favour of the bone origin of hypercalcemia in thyrotoxicosis.
Glucosyl-galactosyl-hydroxylysine and galactosyl-hydroxylysine are two substances present only in collagen and in basement membranes. The purpose of this study is to estimate to what extent the kidney contributes to urinary hydroxylysyl glycoside excretion. "In vitro" perfusion of isolated kidneys allows the measurement of hydroxylysyl glycosides independently of the important amount of interstitial collagen present in the whole body. It is shown that the kidney parenchyma contributes no more than 10 percent of the glycosylated hydroxylysine excreted in urine. GBM is not the only renal source of glucosyl-galactosyl-hydroxylysine in urine. Tubular basement membrane and intersitial collagen of kidney may contribute to the excretion by the isolated organ.
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In vitro studies have suggested that peripheral binding sites (PBR) for benzodiazepine (BZD) could be coupled to the voltage operated calcium channel (VOC) in the heart and that PK11195, an non-BZD ligand with antagonistic activity at this receptors, could inhibit the electrophysiological and mechanical properties of both "peripheral" benzodiazepines and calcium channel blockers. This study evaluates the antidotal value of PK11195 against the cardiovascular depression and arrhythmias in a canine model of acute verapamil intoxication. Although sinus activity is more often preserved or restored (7/8 vs 1/6) in the animals treated with PK11195, this compound, administered in doses able to saturate heart PBR, is unable to prevent or correct the haemodynamic alterations induced by acute verapamil intoxication and the improvement of survival (8/8 vs 3/6) is not significant.
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