[Vitamin A. Some aspects of interest to the pediatrician].
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Adolescent↗
Biomedical subjects
M Rasmussen
Publications and source records attributed to M Rasmussen.
Endoscopic evaluations of potentially ulcerogenic drugs. A new in vivo porcine test model.
A new test model in living pigs is presented. The model is easy to manage and, in contrast with other test models, it is unnecessary to euthanize the animals. The animals keep their value and can be slaughtered later. We advise the use of only one period of 'pill-feeding', because more periods will stress the animals and probably inhibit normal weight gain. We suggest this model as the method of choice in the evaluation of local ulcerogenic effects of drug substances in oral pharmaceutical formulations. An endoscopic evaluation in vivo of the ulcerogenic effect of potassium chloride in different microencapsulated preparations, wax-matrix formulations, a liquid preparation, and a noncoated reference formulation showed one of the microencapsulated preparations to induce a significantly lesser degree of gastric mucosal damage than did all the other preparations. The gastric injury following a slow-release iron preparation and alprenolol (Aptine) was similar to that following the slow-release and the wax-matrix preparations of potassium chloride. Potassium chloride mixture caused gastric mucosal damage to the same extent as the other commonly used preparations of potassium chloride. Potassium chloride supplement causes gastric mucosal damage, but the results from the present in vivo porcine test model suggest that the severity of the injury seems to be a matter of appropriate drug formulation.
Administration, Oral↗
Long-term enhancement of hippocampal synaptic transmission and the acquisition of spatial information.
The hypothesis that memories are stored as a specific distribution of strengths in a population of modifiable synapses was examined by the bilateral induction of long-term enhancement in synapses of the main afferent fiber system to the hippocampal formation in rats. Brief, high-frequency activation of the perforant pathway in chronically prepared animals resulted in a persistent increase in the field EPSP and population spike, measured extracellularly in fascia dentata. This treatment resulted in a profound and persistent deficit in the acquisition of new spatial information in a task requiring spatial "reference" memory, and disruption of recently acquired spatial information. Well-established spatial memory was completely unaffected, however, as was the acquisition of spatial information into short-term "working" memory. These results support the hypothesis that, during the formation of "cognitive maps," spatial information must be temporarily stored at modifiable synapses at the input stage to the hippocampal formation, but that this information is not needed once the representation of the environment is well established. Spatial working memory, in a familiar environment, appears not to depend on the distribution of synaptic strengths in this system at all.
Animals↗
Hepatic retinol metabolism. Distribution of retinoids, enzymes, and binding proteins in isolated rat liver cells.
The main retinoids and some binding proteins and enzymes involved in retinol metabolism have been quantified in different types of rat liver cells. Hepatic perisinusoidal stellate cells contained 28-34 nmol of retinoids/10(6) cells, and parenchymal liver cells contained 0.5-0.8 nmol of retinoids/10(6) cells, suggesting that as much as 80% of more of total liver retinoids might be stored in stellate cells with the rest stored in parenchymal cells. Isolated endothelial cells and Kupffer cells contained very low levels of retinoids. More than 98% of the retinoids recovered in stellate cells were retinyl esters. Isolated parenchymal and stellate cell preparations both contained considerable retinyl palmitate hydrolase and acyl-CoA:retinol acyltransferase activities. Parenchymal cells accounted for about 75-80% of the total hepatic content of these two enzyme activities, with the rest located in stellate cells. On a cell protein basis, the concentrations of both of these activities were much greater in stellate cells than in parenchymal cells. In contrast, cholesteryl oleate and triolein hydrolase activities were fairly evenly distributed in all types of liver cells. Large amounts of cellular retinol binding proteins were also found in parenchymal and stellate cells. Although parenchymal cells accounted for more than 90% of hepatic cellular retinol binding protein, the concentration of the protein in stellate cells (per unit protein) was 22 X greater than that in parenchymal cells. Stellate cells were also enriched in cellular retinoic acid binding protein. Thus, both parenchymal and stellate cells contain substantial amounts of retinoids and of the enzymes and intracellular binding proteins involved in retinol metabolism. Stellate cells are particularly enriched in these several components.
Acyltransferases↗
Retinol esterification in cultured rat liver cells.
Retinol esterification was examined in cultured hepatocytes and stellate cells from the rat. Esterification of [3H]retinol was linear for 2 h in both cell types. By increasing the concentration of retinol in the medium, there was a marked increase in retinol esterification in both cell types. The capacity for esterification of retinol was in the same order of magnitude in the two cell types at 3.5 microM-retinol in the medium. This represents a rate of retinol esterification which far exceeds that required to esterify the amount of retinol absorbed in the intestine. It was demonstrated in particulate homogenates from cultured hepatocytes that the esterification of retinol was dependent on acyl-CoA. Addition of 25-hydroxycholesterol or mevalonolactone promoted an increase in cholesterol esterification, whereas retinol esterification was unaffected, suggesting that cholesterol and retinol are esterified by two different enzymes. Some 80% of vitamin A in cultured hepatocytes is retinyl esters, mostly retinyl palmitate. By adding 87 microM-retinol in the medium the cells accumulated 100-fold free retinol and 2.5-3.0-fold retinyl esters within 1 h. When retinol-loaded cells were incubated without retinol, there was a marked decrease especially in free but also in esterified retinol. In the presence of 1 mM-oleic acid in the medium the amount of retinyl oleate was twice that in control cells.
Acyltransferases↗
Liver retinoids and retinol esterification in fetal and pregnant rats at term.
Retinol esterification in fetal rats and their mothers at term was studied in liver microsomes. The esterification rate was 0.28 +/- 0.05 nmol ester formed per milligram protein per minute, a value somewhat lower than that found in their mothers (0.44 +/- 0.11). The fetuses had significant amounts of liver retinoids. Analysis by high-performance liquid chromatography showed that the retinoid store consisted mainly of retinyl ester both in fetal and adult rat livers, but the fetal livers had higher percentages of free retinol and retinyl oleate than the adult livers. The presence of retinol esterification and a retinyl ester store in fetal rat liver at term is in accordance with the view that retinol brought to liver on retinol-binding protein can be taken up and retained there.
Acetyltransferases↗
Retinol and retinyl esters in parenchymal and nonparenchymal rat liver cell fractions after long-term administration of ethanol.
Chronic ethanol consumption reduces the liver retinoid store in man and rat. We have studied the effect of ethanol on some aspects of retinoid metabolism in parenchymal and nonparenchymal liver cells. Rats fed 36% of total energy intake as ethanol for 5-6 weeks had the liver retinoid concentration reduced to about one-third, as compared to pair-fed controls. The reduction in liver retinoid affected both the parenchymal and the nonparenchymal cell fractions. Plasma retinol level was normal. Liver uptake of injected chylomicron [3H]retinyl ester was similar in the experimental and control group. The transport of retinoid from the parenchymal to the nonparenchymal cells was not found to be significantly retarded in the ethanol-fed rats. Despite the reduction in total retinoid level in liver, the concentrations of unesterified retinol and retinyl oleate were increased in the ethanol fed rats. Hepatic retinol esterification was not significantly affected in the ethanol-fed rats. Since our study has demonstrated that liver uptake of chylomicron retinyl ester is not impaired in the ethanol-fed rat, we suggest that liver retinoid metabolism may be increased.
Acyltransferases↗
The activity of acyl CoA: retinol acyltransferase in the rat: variation with vitamin A status.
Retinol esterification in the small intestine, liver and kidney of rats given a normal diet or a vitamin-A-free diet and of rats given large doses of vitamin A was studied. The active enzyme is a microsomal acyl CoA:retinol acyl transferase (ARAT). In the small intestine ARAT activity was 0.37 nmol ester/mg microsomal protein per min. Large doses of vitamin A increased the activity significantly, while the enzyme activity in the vitamin-A-deficient rats was in the range of that of the controls. Retinoic acid in physiological doses (0.064 mg three times per week) had no influence on ARAT activity. In the liver, ARAT activity of the controls was 0.58 nmol ester/mg microsomal protein per min. The activity was increased after large doses of vitamin A. It was not significantly reduced in vitamin-A-deficient animals. The kidney had a low, but significant ARAT activity, both in normal and vitamin-A-deficient animals and after large doses of vitamin A (range 0.08-0.14 nmol ester/mg microsomal protein per min). The vitamin-A-esterifying enzyme in the small intestine and liver of the rat seems to be influenced by the amount of retinol in the diet.
Acyltransferases↗
Microsomal esterification of retinol in human liver.
Recent work has shown that esterification of retinol in microsomes from rat liver, mammary gland and small intestine and from human small intestine is catalyzed by an acyl CoA: retinol acyl transferase (ARAT). The current study demonstrates ARAT activity in human liver microsomes. At optimal incubation conditions the rate of retinyl ester formation due to ARAT (0.37 +/- 0.31 nmole ester formed X mg microsomal protein-1 X minute-1, mean +/- SD, n = 6) suggests that the enzyme is of physiological importance.
Acyltransferases↗
Storage of mixtures for total parenteral nutrition. II. Microbiological control of large volume TPN mixtures.
Microbiological control of TPN mixtures can be performed either by controlling the aseptic filling procedure using culture medium instead of intravenous solutions, or by an end-product sterility test. A microbiological process control of the filling procedure is described, and it is shown that a hospital pharmacy can prepare 3-litre bags without contamination. The number of 3-litre bags necessary in the process control is discussed, as well as the frequency with which a control should be performed. A possible non-destructive system for testing each 3-litre bag microbiologically is outlined and discussed. This system may be used when TPN mixtures without lipid emulsion are stored for longer periods.
Culture Media↗
Storage of mixtures for total parenteral nutrition III. Stability of vitamins in TPN mixtures.
TPN mixtures should contain all nutritional element necessary in the nutritional therapy--including unstable vitamins. In this study the stability of ascorbic acid and folic acid was investigated in a TPN mixture containing 12 vitamins by HPLC and microbiological assays. The degradation of both vitamins proceeded by first order kinetics. Half-lives for ascorbic acid were 1.1 h, 2.9 h, and 8.9 h when stored at 24 degrees C by daylight, 24 degrees C protected from light, and 4 degrees C protected by light, respectively. Under similar conditions half-lives for folic acid were 2.7 h, 5.4 h, and 24 h. The degradation rates found make pre-addition of these two vitamins to TPN mixtures questionable, storage for longer periods is inappropriate. For TPN patients receiving additional fluid intravenously it was found that addition of multivitamins to isotonic NaCl-solution was advisable. For other TPN patients alternative ways of vitamin administration might be preferable. When testing the stability of vitamins in TPN mixtures it was found that the brand of multivitamin preparation used was of importance. It should be stressed that data on the stability of vitamins derived from studies on the addition of a single vitamin cannot be extrapolated to multivitamin preparations because of possible mutual vitamin interactions.
Ascorbic Acid↗
[Prescription or treatment?].
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Age Factors↗
Storage of mixtures for total parenteral nutrition--long-term stability of a total parenteral nutrition mixture.
A TPN mixture containing amino acids, dextrose, electrolytes, and trace elements was analysed dor chemical stability during storage at 4 degrees C for 6 months. Dextrose, electrolytes, and trace elements appeared to be stable during the storage period. However, this study established that some amino acids were not stable for more than 2 months. After 6 months, the amino acids except tyrosine, lysine, and histidine were degraded by more than 10%. The most pronounced degradation was seen with alanine, proline, threonine, methionine, glycine, and arginine. Tryptophan was, in spite of the presence of bisulphite, one of the more stable amino acids. Further investigations are needed to identify the degradation products. pH and colour of the solution remained unchanged during the study and no precipitation was observed.
Amino Acids↗
In vivo uptake of chylomicron [3H]retinyl ester by rat liver: evidence for retinol transfer from parenchymal to nonparenchymal cells.
We have studied hepatic uptake of chylomicron retinyl ester. Chylomicrons were obtained from intestinal lymph of rats that were given retinol in groundnut oil by intraduodenal injection. When lymph was injected intravenously into normal rats, the radioactivity was cleared from blood with t1/2 approximately equal to 10 min. Retinyl ester was taken up initially by the liver, which, after 30 min, contained 80-90% of the radioactivity injected. Initially, most of the radioactivity was in hepatocytes, but after 30 min it disappeared from these cells and reappeared in nonparenchymal liver cells. After 2 hr these cells contained more radioactivity than the hepatocytes. When lymph was injected into vitamin A-deficient rats or rats given vitamin A in the form of retinoic acid, the plasma clearance and initial hepatic uptake of radioactivity were similar to that found in control animals. However, the nonparenchymal cells in these animals did not accumulate radioactivity. The current data suggest that vitamin A (in chylomicron remnants) is taken up initially by hepatocytes and then is released from these cells and delivered mainly to nonparenchymal liver cells in normal animals. In vitamin A-deficient rats, the vitamin is transferred from the hepatocytes to extrahepatic tissues.
Animals↗
A possible model for accuracy control of determination of serum cholesterol with use of reference methods. A NORDKEM project.
A candidate definitive method for determination of total serum cholesterol developed at the Center for Analytical Chemistry, National Bureau of Standards, USA, has recently been compared with a reference method based on isotope dilution-mass spectrometry, developed at Huddinge Hospital. There was no significant difference (0.2%) in results obtained with the two methods. The Huddinge method was used here for assessment of inaccuracy of a defined enzymatic method, set up and used at four laboratories, one in each of four Nordic countries. The results obtained in the analysis of 21 patient samples were not significantly different from those obtained with the isotope dilution method. In the analytical range 1.7-14.2 mmol/1, the regression equation for the defined enzymatic method (y) versus the isotope dilution method (x) was y = 0.994x - 0.06 and the correlation coefficient 0.9999. The mean between-laboratory variation for the defined enzymatic method was 2.3%. The possibility is discussed that the defined enzymatic method can be used as candidate secondary reference method for assessment of inaccuracy of field methods in national quality control activities. In such a control system, the accuracy can be traced back to the definitive methodology through the hierarchical system.
Cholesterol↗
Blood-brain glucose transport in the conscious rat: comparison of the intravenous and intracarotid injection methods.
The unidirectioal transfer of D-glucose from blood to parietal cortex tissue of the brain of awake rats was measured by single intravenous injection of tracer glucose, as well as by single intracarotid injection according to the method of Oldendorf. The maximal unidirectional blood-brain glucose transfer rate (Tmax) was 407 mumol (100 g)-1 min-1 when measured by intravenous injection, and 352 mumol (100 g)-1 min-1 when measured by intracarotid injection. The half-saturation constants (Km) were 7.8 mM and 16.8 mM, respectively. The comparison shows that the two methods give similar results when cerebral perfusion is assessed accurately.
Animals↗
Pentobarbital anesthesia reduces blood-brain glucose transfer in the rat.
Pentobarbital anesthesia (40 mg kg-1) was accompanied by a 50% decrease of blood flow and a 40% decrease of unidirectional blood-brain glucose transfer in the parietal cortex of the rat brain. The correlation was explained by a decrease of the number of perfused capillaries. The maximal transport capacity, Tmax, decreased from 409 to 235 mumol 100 g-1 min-1 and the half-saturation constant, Km, from 8.8 to 4.9 mM. At 8.3-8.7 mM-glucose in arterial plasma, the transfer constant (clearance) for unidirectional blood-brain transfer decreased from 0.195 +/- 0.011 in awake rats to 0.132 +/- 0.005 ml g-1 min-1 in anesthetized rats. Half of the decrease was due to less complete diffusion-limitation of glucose uptake at the low plasma flow rate in brain, the other half to the decreased Tmax.
Animals↗
[Early contact with parents of mentally handicapped children. Secondary prevention aspects].
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Child↗