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Biomedical subjects

H Weiser

Publications and source records attributed to H Weiser.

At least 73 records · Page 4Linked to original sources

Biological activity of 1 alpha,25-dihydroxyergocalciferol in rachitic chicks and in rats.

The bioactivity of chemically synthesized 1 alpha,25-dihydroxyergocalciferol (1,25(OH)2D2) was investigated in rachitic chicks and in vitamin D-deficient rats. In prophylactic and in curative chick assays 1,25(OH)2D2 is about 10 times less active than 1 alpha,25-dihydroxycholecalciferol (1,25(OH)2D3). Since in the same bioassay vitamin D2 is more than 80 times less active than vitamin D3, discrimination against vitamin D2 in chickens must occur at two points, before and after the formation of 1,25(OH)2D2. Receptor binding studies revealed that the chick duodenal receptor binds 1,25(OH)2D2 with the same capacity as 1,25(OH)2D3. In rats 1,25(OH)2D2 proved to have the same antirachitic activity as 1,25(OH)2D3 and might become of therapeutic interest for application in man and domestic animals if the expectations of lower toxicity are confirmed.

Animals↗

Urinary cholesterol: its association with a macromolecular protein-lipid complex.

The cholesterol-containing complexes in the urine of normal subjects and patients with diseases accompanied by hyperexcretion of urinary cholesterol were characterized. In normal subjects, the major portion of the recovered urinary cholesterol was eluted in the void volume fractions after gel chromatography on Bio-Gel A-5m; this suggested an association with a macromolecular complex above 5 X 10(6) daltons. A comparable elution pattern was seen in most of the urines of the patients with benign or malignant diseases of the kidneys or the urogenital tract. However, in single patients with hyperexcretion of urinary cholesterol, considerable amounts of cholesterol were detected in the included volume of the column. This was caused by additional excretion of high density lipoproteins or both high and low density lipoproteins in the urine which could be identified in these fractions by agarose electrophoresis and immunodiffusion. These results indicate that the macromolecular complex represents the majority of the recovered urinary cholesterol in normal subjects and in disease states with known hyperexcretion. Macroscopically, the isolated cholesterol-containing complex in the void volume fractions was turbid, and electron microscopy showed lipoprotein-like particles with diameters ranging from 300 to 700 A. The chemical analysis revealed median values of protein (46.0%), triglycerides (16.3%), cholesterol (8.2%), and phospholipids (29.5%) in normal subjects and comparable results in the patients with benign or malignant diseases of the kidney and the urogenital tract. Ethanolamine glycerophospholipids, phosphatidylcholine, sphingomyelin, and phosphatidylserine were the main phospholipid components. After ultracentrifugation in a CsCl gradient, the cholesterol-containing complex was found between densities 1.1 and 1.3 g/ml. By SDS polyacrylamide electrophoresis, up to 17 protein subunits in the molecular weight range of 14,000 to 87,500 were separated. Immunodiffusion studies showed in about 40% precipitin lines against anti-human albumin, but no reactions against anti-human apoHDL and anti-human apoLDL. However, immunodiffusion of the macromolecular complex against anti-liver-specific and anti-kidney-specific lipoproteins revealed single precipitin lines. In conclusion, the isolated cholesterol-containing urinary complex showed many characteristics of membrane-associated protein-lipid particles of the human kidney and even the liver. These proteolipids are the major source of urinary cholesterol in normal and disease states.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Biological activity of glycosides of vitamin D3 and 1 alpha-hydroxyvitamin D3.

For the first time, the biological activity of the newly synthesized glycosides of vitamin D3 and of 1 alpha(OH)D3 has been studied in rats, chickens, and Japanese quails. Glucosidation did not reduce the activity of vitamin D3. In chickens, vitamin D3 glucoside has an activity of 90% to 95% as compared to the aglycon. In rats vitamin D3 glucoside is equally active when given by intravenous or oral route. Glycosides of 1 alpha (OH)D3, however, show a lower activity in rats, chickens, and quails. 1 alpha (OH)D3 glucoside has about 10% activity of the free 1 alpha (OH)D3, while 1 alpha (OH)D3 cellobioside is without any activity in chickens. 1 alpha (OH)D3 glucoside might be of interest, due to its broader therapeutical dosage range.

Administration, Oral↗

Influence of vitamin A deficiency on the excretion of uromucoid and other substances in the urine of rats.

Male Fü-albino rats were weaned at the age of four weeks and maintained on a vitamin A-deficient diet. When they were 14-18 and 21-26 weeks old, the concentration of uromucoid, calcium and other substances possibly important for the pathogenesis of urinary calculi were determined. Reduced uromucoid excretion with hypercalciuria and reduced phosphate levels were observed. Subsequent examination of the kidneys did not demonstrate the presence of nephrocalcinosis or lithiasis. The relation between vitamin A, the synthesis of uromucoid and AMPS and calcium metabolism in the renal tubules is discussed.

Albuminuria↗

Biopotency of vitamin K. I. Antihemorrhagic properties of structural analogs of phylloquinone as determined by curative prothrombin time tests.

Relative antihemorrhagic properties of structural analogs of transphylloquinone (vitamin K1) have been determined by curative prothrombin time tests with vitamin K-deficient chicks. Analogs (where applicable) and the phylloquinone standard had (all-) rac-trans configuration, and all compounds were well characterized (structure, purity, trans: cis). Compounds were administered as single oral doses according to the up-and-down procedure. Estimation of mean effective doses allowed a reliable calculation of relative activities for analogs in comparison with vitamin K1 standard. 2', 3'-Dihydro-phylloquinone had a relative activity of only 6.7%, i.e. it was about 15 times less active than phylloquinone. Further reduction of this analog led to 2',3',5,6,7,8-hexahydro-phylloquinone which was completely inactive. Analogs with oxygen functions in the side chain, 6'-hydroxy-K1, 6'-oxo-K1, and 7'-hydroxy-6'-oxo-K1, displayed relative activities of 20.5%, 31.9%, and 30.5%, respectively. Phylloquinone-2,3-epoxide was 1.7 times more active than the phylloquinone standard. An analog with a 7-carbon side chain ending with a carboxy group (in mammals a urinary metabolite of vitamin K1) and its corresponding ethyl ester derivative were practically inactive.

Animals↗

Stereoisomers of alpha-tocopheryl acetate--characterization of the samples by physico-chemical methods and determination of biological activities in the rat resorption-gestation test.

Stereoisomers of alpha-tocopheryl acetate (alpha-TA) have been identified and characterized by means of a recently developed gas-liquid chromatographic technique prior to the determination of their biopotency. It has been shown that totally synthetic all-rac-alpha-TA (dl-alpha-TA) is composed of four pairs of diastereomers (RRS-SSR, RRR-SSS, RSR-SRS, RSS-SRR) in virtually equal proportions. In addition, it has been verified that 2-ambo-alpha-TA (partially synthetic, ex phytol) is an equimolar mixture of RRR-alpha-TA and 2 epi-alpha-TA. Finally, it has been demonstrated that the RRR-alpha-TA (d-alpha-TA) tested was diastereomerically pure. The biopotencies of these alpha-tocopheryl acetate stereoisomers have been evaluated by standardized rat resorption-gestation test. Our first study concerned the comparison of all-rac-alpha-TA with RRR-alpha-TA and resulted in a potency ratio of 1:1.50 or 1:1.48. The first value was derived from the amounts weighed out while the second value was based on the analytically determined alpha-TA content of the stock solutions. Similarly, the comparison of 2-ambo-alpha-TA with RRR-alpha-TA yielded potency ratios of 1:1.32 (amount weighed out) and 1:11.36 (alpha-TA analysed). The influence of the configuration of the side-chain on biopotency has been analysed by a second series of investigations. Comparison of all-rac-alpha-TA with 2-ambo-alpha-TA resulted in a biopotency ratio of 1:1.09 (amount weight out) and 1:1.10 (alpha-TA analysed). However, these slightly higher values for 2-ambo-alpha-TA did not reach statistical significance. These studies demonstrate the validity of the established potency ratio of 1:1.36 for 2-ambo-alpha-TA to RRR-alpha-TA by direct comparison of these compounds. In addition, the experimental ratios for all-rac-alpha-TA to 2-ambo-alpha-TA and for all-rac-alpha-TA to RRR-alph-TA can be grouped into the expression (1:1.10)/(1:1.48) = 1.35. This indirect comparison further supports the accepted value of 1.36 USP Units for 1 mg d-alpha-tocopheryl acetate.

Animals↗

Ascorbic acid and cholesterol: effect of graded oral intakes on cholesterol conversion to bile acids in guinea-pigs.

A significant correlation between liver ascorbic acid (AA) and total bile acids or liver bile acids has been established in guinea-pigs by direct determination of the bile acids, confirming an earlier hypothesis. The oxidation of cholesterol to bile acids is dependent on the AA status, but it cannot be further stimulated by AA when the animals are already on an adequate intake of the vitamin. This suggests that AA has a hypocholesterolaemic effect over a limited range of AA status.

Animals↗

Interaction of erythorbic acid with ascorbic acid catabolism.

After a vitamin C depletion period of 12 days supplementing erythorbic acid (50 mg/day/kg bodyweight) over 16 days significantly accelerated the catabolism of a newly ingested tracer dose of (1-14C) ascorbic aicd in guinea pigs in comparison to animals supplemented with ascorbic acid (5 mg/day/kg bodyweight), but this effect of erythorbic acid could not be normalized by additional supplementation with ascorbic acid. Half-lives for (1-14C) ascorbic acid (50% of the dose excreted) were drastically reduced from 97 h to 50 h and 59 h, respectively. Also figures on the retention of radioactivity showed the availability of ascorbic acid to be reduced. This is in accordance with the significant reduction in size of ascorbic acid bodypool, and in weight gain in the groups receiving erythorbic acid, or erythorbic and ascorbic acids. The bioavailability was calculated to be strongly depressed to nearly 50% of the total ingested biologically active material (ascorbic plus erythorbic acids), assuming erythorbic acid to have only one-twentieth of the biological activity of ascorbic acid.

Animals↗

Cerebral monoamine metabolism in guinea-pigs with ascorbic acid deficiency.

Guinea-pigs kept on a diet deficient in vitamin C showed, after 3 weeks, a marked decrease of ascorbic acid in brain and blood leucocytes as well as of the activity of alkaline phosphatase in blood plasma. Pair-fed animals did not exhibit these changes. The alpha-methyl-p-tyrosine (alpha MpT)-induced diminution of noradrenaline in the hypothalamus and the rest of the brain was attenuated in pair-fed animals, but restored in guinea-pigs deficient in ascorbic acid. The cerebral noradrenaline content (without administration of alpha MpT) showed a decrease in both pair-fed and ascorbic acid deficient animals. The noradrenaline of the heart exhibited a similar tendency. The alpha MpT-induced dopamine decrease in the striatum of ascorbic acid deficient animals was attenuated and the dopamine content (without alpha MpT administration) decreased. Pair-fed animals showed a similar tendency. The striatal concentration of homovanillic acid (HVA) was diminished in both pair-fed and ascorbic acid deficient guinea-pigs. The cerebral content of 5-hydroxyindoleacetic acid showed a decrease in pair-fed as well as in ascorbic acid deficient animals. It is concluded that ascorbic acid deficiency enhances the turnover of brain noradrenaline, whereas under-nutrition without ascorbic acid deficiency (pair-feeding) diminishes the turnover of cerebral noradrenaline, 5-hydroxytryptamine and striatal dopamine.

Alkaline Phosphatase↗