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Biomedical subjects

H Weiser

Publications and source records attributed to H Weiser.

At least 37 records · Page 2Linked to original sources
PubMed1989

[The importance of animal models for progress in science].

Experimental animals may serve as models for human beings, if analogies between animal and human functions exist. Therefore, the selection of species and strain plays an important role in the development of such models. Knowledge of the nutritional and physiological characteristics of a species is a prerequisite for the composition of complete diets. Often, preliminary work has to begin at the breeding farm in order to make use of such curative models possible. Only when the high requirements of standardization of experimental animals are met can clinical and subclinical symptoms be determined distinctly. By means of sensitive biochemical reactions, imbalances and interactions of nutritive and active ingredients, as well as successful substitutions, can be recorded. The study of absorption and metabolism of preparations is made possible by observing these reactions. However, negative influence on the results of analysis must be eliminated by correct selection of narcotics, and the proper excision and storage of organs. Because of its importance for the planning and evaluation of experiments, biometry is an integral part of every research project. The scientific information which must be gained from the whole experimental animal cannot be substituted by either isolated organs and cell cultures, or by means of computer simulation. A demanding effort, which includes biotechnological methods, is necessary to further reduce the number of experimental animals and, simultaneously, to enhance experimental evidence. In any case, all scientific aims must be in accordance with the ethical principles of the Society for the Prevention of Cruelty to Animals.

Animal Feed↗
PubMed1989

Vitamin A in parenteral nutrition: uptake and distribution of retinyl esters after intravenous application.

Short-term parenteral application of vitamin A was examined in rats. Retinyl margarinate, which is chemically similar to physiological retinyl esters, was used in vitamin A-depleted rats to study uptake, distribution, and storage of retinyl esters in tissues. Vitamin A-depleted and Vitamin A-sufficient rats were infused with a micellar suspension of retinyl margarinate for 7 h and then killed at different times. Retinyl margarinate was directly taken up by all tissues examined. It appears that infusion of retinyl esters in micellar form provides a direct way to supply vitamin A to peripheral, vitamin A-dependent tissues. Therefore, a short-term infusion of retinyl esters with an emulsifier may be an effective means of preventing development of vitamin A-deficiency during long-term application of TPN, particularly in cases of liver dysfunction.

Animals↗
PubMed1989

Sensitive analysis of retinyl esters by isocratic adsorption chromatography.

A sensitive method for the determination of retinyl esters, including their geometric isomers, by isocratic adsorption HPLC is described. The development of a special recycling system allows the separation of all-trans-, 13-cis, 11-cis- and 9-cis-retinyl palmitate, -stearate, -oleate, -palmitoleate and -linoleate with short retention times and high sensitivity. Extraction of the retinyl esters from various organs with mobile phase avoids additional evaporation steps. The method was evaluated by the determination of retinyl esters in small tissue samples such as tongue, trachea and inner ear. This is the first report of the detection of retinyl esters in these tissues, which are known to depend on an adequate vitamin A supply. The main ester in all cases was retinyl palmitate, followed by retinyl stearate and oleate.

Animals↗
PubMed1989

Pyridoxine status as assessed by the concentration of B6-aldehyde vitamers.

Forty-five male Lohmann chicks were randomly assigned to an adequate (30 mumol PN/kg) or a B6-deficient diet. Chicks were grown to 6 weeks of age and the vitamin B6 status was assessed according to the level of B6-aldehyde vitamers in plasma and erythrocytes. Chicks fed a limited amount of pyridoxine showed no nervous signs, but significant metabolic changes. It was found that PL was the major metabolite in plasma and only a trace of PLP was detected, suggesting a different metabolic pathway from those of other animal species or healthy humans. This particular metabolism parallels an elevated ALP concentration. The measurement of plasma PLP level routinely used for the assessment of vitamin B6 status in humans is misleading in a situation with raised ALP.

Animals↗
PubMed1988

Synergistic effects of vitamin D metabolites.

The vitamin D3 metabolites 1 alpha,24R,25- and 1 alpha,25S,26-trihydroxy vitamin D3 and their combinations with 1 alpha,25-dihydroxy vitamin D3 were tested for antirachitic activity in rats, chicken and Japanese quails. The trihydroxylated compounds were found to increase the activity of 1 alpha,25-dihydroxy vitamin D3. Since this synergistic effect is restricted to calcium absorption and bone formation while bone calcium mobilization is unchanged, the combined administration might improve calcium balance. These findings raise the possibility of a more efficient therapy of vitamin D-dependent diseases with limited amounts of 1 alpha,25-dihydroxy vitamin D3.

Animals↗
PubMed1988

Is pyridoxine an essential nutrient for bone?

Plasma PLP and PL levels were drastically reduced in the B6-deficient group. The plasma and erythrocyte activities of AspAT were depressed by 35 and 15%, respectively. The B6-deficient diet also produced a slight decrease in the plasma levels of AP (holoenzyme and bone isoenzyme) and OH-Pro. This change was accompanied by a slight increase of Pi A negative correlation was found between plasma AP and PLP.

Alkaline Phosphatase↗
PubMed1986

Biological activity of fluorine-substituted 1,25-dihydroxyvitamin D3 in rats, in chicken and in Japanese quails.

The biological activity of two fluorinated analogs of 1,25(OH)2D3 was compared with 1,25(OH)2D3 in various vitamin D assays. The effect of 24,24-F2-1,25(OH)2D3 on plasma calcium, bone weight and duodenal calcium binding protein in chicken, on calcium excretion via egg shell in Japanese quails and on mobilization of calcium from the bone in rats was twice as high as the effect of the most potent naturally occurring vitamin D3 metabolite 1,25(OH)2D3. In contrast, 24R-F-1,25(OH)2D3 has less than 50% of the potency of 1,25(OH)2D3. Due to the wider therapeutic dosage range, this compound might be of clinical value.

Animals↗
PubMed1986

Stereoisomers of alpha-tocopheryl acetate. IV. USP units and alpha-tocopherol equivalents of all-rac-, 2-ambo- and RRR-alpha-tocopherol evaluated by simultaneous determination of resorption-gestation, myopathy and liver storage capacity in rats.

Whereas the alpha-tocopheryl acetate (alpha-TA) stereoisomers have frequently been compared in various vitamin E tests, only little studies have been made on the free alpha-tocopherols. For this reason, comparative tests of the alpha-tocopherol (alpha-TOH) stereoisomers were made by means of the resorption-gestation method, not only individually but also against the USP standard all-rac-alpha-TA. In some of these tests, the parameter resorption-gestation was supplemented by determination of pyruvate kinase (PK) activity as well as by measurement of the vitamin E level in the liver. Quantitative statistical evaluation of the results was made by weighted probit analysis or by symmetrical parallel line assays. Comparison of all-rac-alpha-TOH (dl-alpha-TOH) with RRR-alpha-TOH (d-alpha-TOH) in the resorption-gestation test revealed an activity ratio of 1:1.38. Compared with 2-ambo-alpha-TOH, RRR-alpha-TOH was more active by a factor of 1.34 (resorption-gestation) or 1.45 (myopathy). On account of its great importance in practice, the comparison between RRR-alpha-TOH and the USP standard was repeated three times. With the parameters resorption-gestation and myopathy, mean activities on a weight basis of 0.69 and 0.74, respectively, were measured. These results fail to confirm the established activity of 1 mg RRR-alpha-TOH = 1.49 USP units. If vitamin E activity is to be given in alpha-tocopherol equivalents (alpha-TE), the values are referred to RRR-alpha-TOH and the calculation is made with their reciprocals. Depending on the parameter used, the activity of 1 mg all-rac-alpha-TA was equivalent to 1.45 alpha-TE (resorption-gestation) or 1.35 alpha-TE (myopathy) and was thus noticeably higher than the established value of 0.67 alpha-TE. For the first time, three parameters were determined simultaneously in the comparison of all-rac-alpha-TOH with the USP standard. Quantitative evaluation yielded the following activities: Resorption-gestation, 0.52; Myopathy, 0.63; liver storage, 0.68. The currently accepted value of 1.10 USP units for 1 mg all-rac-alpha-TOH was thus not even reached approximately. In the light of our experimental findings as well as of those of other laboratories, the activities of the alpha-tocopherol stereoisomers expressed in USP units and of their esters expressed in alpha-tocopherol equivalents need to be corrected.

Animals↗
PubMed1985

[Uptake and distribution of 14C-retinyl acetate in organs and sensory tissue (inner ear) of the guinea pig].

The uptake and chemical identification of 14C-retinyl acetate in the inner ear of the guinea-pig after oral administration is reported. For methodological reasons the experiment was carried out in vitamin A-deficient guinea-pigs. In the sensory tissues a time-dependent distribution was found similar to that in other organs. The chemical identification shows that the orally administered labeled retinyl acetate can be detected as retinyl palmitate in the membranous structures of the inner ear. This may be an indication for the ability of the inner ear tissues to esterize and probably store the transport form of vitamin A, retinol.

Administration, Oral↗
PubMed1985

Retinol deficiency and Dipetalonema viteae infection in the hamster.

Following chronic retinol (vitamin A) deprivation leading to exhaustion of liver vitamin A reserves below 50 I.U. per liver hamsters were fed diets either deficient in ("Rd":250 I.U.A./kg in experiment I, 1000 I.U.A/kg in experiment II) or enriched with retinol ("Rw":10000 I.U.A/kg in experiment I and II). After 4 weeks some of the animals (36 in experiment I, 30 in II) were infected with 150 3rd-stage larvae of D. viteae, while clean animals were kept as controls. The retinol status, the immune response (indirect fluorescent antibody test: IFAT) and parasitological parameters were examined up to 8 (experiment I) and 12 weeks (experiment II) post infection (p.i.). Rd hamsters had levelling off of weight gain or weight loss, severely deficient retinol levels in serum and liver, and high mortality. Weight gain was less in infected than in uninfected hamsters, and the capacity of infected Rw animals to restore liver retinol was significantly lower than that of uninfected Rw animals. IFAT titres were similar in Rd and in Rw animals, but microfilaraemia was significantly enhanced at 8 and 10.5 weeks p.i. in Rd hamsters. While the number of worms recovered from Rd and Rw hamsters was similar, there was a significant increase in the ratio of female to male worms in Rd hamsters. Rd hamsters in experiment I produced 3.3 times the worm mass per 100 g body-weight than Rw hamsters. Also, the average mass per female worm was significantly higher in Rd than Rw in hamsters, and this parameter was negatively correlated with the liver retinol concentration in experiment I(r = -0.89). Retinol deficiency has a marked effect on growth and fertility of D. viteae in hamsters.

Animals↗
PubMed1985

Biological activity of the three mono-beta-D-glucopyranosides of 1,25-dihydroxycholecalciferol.

The biological activity of the three mono-beta-D-glucopyranosides (mono-glucosides) of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] synthesized chemically has been studied in chicks and Japanese quails. While the 1- and the 3-glucoside showed no or only little effect on serum calcium, bone weight, calcium binding protein (CaBP) or calcium deposition in the egg shell, the 25-glucoside was found to be more than half as active as the aglycone 1,25(OH)2D3. The bioactivity of this glucoside parallels a higher binding constant to the intestinal 1,25(OH)2D3 receptor compared to those of the two other glucosides.

Animals↗
PubMed1985

The vitamin A activity of beta-carotene.

In rats (parameters: growth, epithelial protection and liver storage), and in chicks (liver storage), it has been demonstrated that the conversion of beta-carotene to vitamin A diminishes inversely to the intake of beta-carotene, as long as the dosages are higher than 1-2 times the daily requirements. The decrease in the biopotency of beta-carotene follows a Michaelis Menten kinetic. In the dosage range of the daily requirements molecular ratio applies. Based on these findings, the following guidelines for the conversion of retinol in man are proposed: (Table: see text). For beta-carotene in oily solutions, a conversion factor of 1:3.33 should be accepted for the dosage range of 1,500 to 4,000 micrograms. For higher doses, this factor should be decreased according to the results with laboratory animals: For beta-carotene in vegetables, the conversion factor of 1:6.0 should be accepted for intakes between 1,500 and 4,000 micrograms. A higher factor should be chosen for smaller intakes, and a smaller factor for higher intakes.

Animals↗
PubMed1985

Stereoisomers of alpha-tocopheryl acetate. III. Simultaneous determination of resorption-gestation and myopathy in rats as a means of evaluating biopotency ratios of all-rac- and RRR-alpha-tocopheryl acetate.

The resorption-gestation test furnishes information on a more complex vitamin activity than is the case with other vitamin E tests, so that correspondingly more importance attaches to the results. A drawback is their questionable validity for species other than the small rodents in which fetal resorption has so far been observed. In the four experiments carried out, RRR-alpha-tocopheryl acetate (alpha-TA) was compared with all-rac-alpha-TA (USP standard) and a mean relative activity of 1.32 was determined. The additional measurement of pyruvate kinase (PK) activity serves to emphasize the correlation with nutrition-linked myopathy. This biochemical lesion is seen in various animal species and man. In two experiments, the parameters fetal resorption and plasma PK activity were measured together. For all-rac-alpha-TA and RRR-alpha-TA, the following activity ratios were calculated: Resorption-gestation 1:1.35; Myopathy 1:1.47. It could be shown that the two parameters are measurable quantitatively in a single experimental set-up and that the results are in good agreement. The accepted activity of 1 mg RRR-alpha-TA = 1.36 USP Units was fully confirmed.

Animals↗
PubMed1984

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↗
PubMed1984

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↗