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Biomedical subjects

H Weiser

Publications and source records attributed to H Weiser.

At least 55 records · Page 3Linked to original sources
PubMed1990

Vitamin A deficiency increases noise susceptibility in guinea pigs.

The effect of vitamin A deficiency in guinea pigs on noise-induced temporary threshold shift (TTS) was evaluated after short (15 min) acoustic overstimulation with a moderate (90 dB) broad-band white noise. Some guinea pigs were fed ad libitum a purified diet deficient in vitamin A (VAD group) until biochemical signs of deficiency occurred. A second, control group (VA group) received the same diet as well as 100 IU vitamin A daily by pharyngeal tube. Cochlear potentials were recorded by special computerized equipment using implanted electrodes. Before acoustic stimulation, a baseline value was determined with a test stimulus [90 dBA (A-filter according to usual DIN instructions)] corresponding to that for TTS measurements. Noise-induced changes were determined by calculating the changes in latency and amplitude of the N1-signal of the compound action potential (CAP) at various times (1, 3, 5, 7, 11 min) after termination of acoustic stimulation in comparison with baseline values. Statistical analysis of the CAP data showed that the VAD group had significantly smaller amplitudes and increased latency of the N1-potential after acoustic stimulation and that the VA group did not show a significant change in amplitude or latency. The reduction in N1-amplitude and N1-latency in the VAD group reflects changes in inner ear hair cell activity. We conclude that vitamin A deficiency increases the sensitivity of the inner ear to noise and that this increased sensitivity increases the probability of noise-induced hearing loss.

Acoustic Stimulation↗
PubMed1990

Morphological abnormalities in vitamin B6 deficient tarsometatarsal chick cartilage.

The aim of this study was to test the hypothesis that deficiency of vitamin B6 would produce morphological characteristics of osteochondral lathyrism. To accomplish this goal, morphological characteristics of chick cartilage in which lathyrism was produced by two separate dietary regimens was compared to morphological changes encountered in vitamin B6 deficiency. Vitamin B6 deficiency should reduce activity of lysyloxidase needed for producing intermolecular cross-links. The question to be addressed was: would this latter deficiency impair collagen morphological features and secondarily other structures indirectly by reducing collagen molecular assembly? Failure of cross-linking of collagen in the positive controls was related to a lack of functional aldehyde cross-link intermediates which are blocked by homocysteine and aminoacetonitrile. Day-old-male Lohmann chicks were fed adequate (6 mg/kg) or vitamin B6-deficient diets. Cross-link defects were induced by homocysteine-rich diets (0.6% w/w) or a diet containing aminoacetonitrile (0.1% w/w). Animals were sacrificed at 6 weeks of age and Ossa tarsalia articular cartilage specimens, as well as the proximal end of tarsometatarsus were dissected from the tibial metatarsal joint, a major weight-bearing site. Light microscopic observations revealed reduction of subarticular trabecular bone formation, concurrent with overexpansion of the hypertrophic cell zone. Ultrastructural electron microscopy observation of articular fibro-cartilage indicated significant thickening of collagen fibers in vitamin B6 deficient birds, as well as the positive controls in comparison to that of cage-matched control birds. It was concluded that vitamin B6 deficient cross-linking may be responsible for the observed delay in bone development and aforementioned cartilage histological alterations.

Aminoacetonitrile↗
PubMed1990

Uptake and metabolism of retinoic acid induces inhibition of cell growth: a study in a rat rhabdomyosarcoma cell line (BA-HAN-1C) using nonlinear theoretical models.

Retinoic acid causes a significant inhibition of cell growth of the tumor cell line BA-HAN-1C. This growth inhibition is the same whether the cells are treated with a pulse dose of retinoic acid (RA) or continuously expand to RA. The determination of RA and its degradation products within the culture medium and in the cells showed that after 24 hours 13-cis-RA was the major retinoid in all cells (96 ng/10(6) cells); all-trans-RA represented 56 ng/10(6) cells. After 48 hours 4-hydroxy-RA and a small amount of 5,6-epoxy-RA was found in the cells and also in the culture medium. 4-hydroxy-RA increased up to 96 hours, whereas 13-cis- and all-trans-RA were not detectable in the cells after 96 hours. We conclude that the BA-HAN-1C cells take up and metabolize RA. Nonlinear fit analysis of the time behavior of the RA concentration in medium demonstrates that the RA uptake unexpectedly follows a mono-exponential time function. Discussion of the experimental results in connection with a proper compartment model shows that uptake and metabolism of RA cannot be described really by a first order kinetics. The mathematical analysis leads to a more complicated kinetic model with certain restrictions for the corresponding rate constants.

Animals↗
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↗