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Biomedical subjects

A Vahlquist

Publications and source records attributed to A Vahlquist.

At least 109 records · Page 6Linked to original sources

Vitamin A transporting proteins in human epidermis and blister fluids.

In connection with studies on vitamin A transport to keratinocytes in vivo, the retinol, retinol-binding protein (RBP), and prealbumin contents of blister fluid obtained subepidermally (suction) or intraepidermally (friction) were analyzed. The median concentrations of the three components in suction blister fluid (SBF) were all about 33% of the serum concentrations. Corresponding values for alpha 2-macroglobulin and total protein, measured as controls, were 27 and 30%, respectively. The relative amounts of retinol and prealbumin in friction blister fluid (FBF) were the same as those in SBF. By contrast, FBF contained more RBP (median value 40%; P less than 0.01 vs SBF value). It is suggested that apo-RBP (RBP without retinol) is generated within the epidermis and contributes to the high RBP value in FBF. FBF constituents are probably derived from the intercellular space of the epidermis, at least during the initial phase of blister formation. Accordingly, RBP and prealbumin were identified in homogenates of pure epidermis. During the later stages of blister formation, FBF resembles an ultrafiltrate of dermal fluid, although different in this respect from SBF.

Adult↗

Retinoid concentrations in skin, serum and adipose tissue of patients treated with etretinate.

Synthetic and natural retinoids were analysed in epidermis, dermis, subcutis and serum of twenty-seven patients treated with etretinate (0.6-1.0 mg/kg/day) for 1-36 months. The concentrations of etretinate (including its major metabolite) in serum and normal-appearing epidermis were 150-600 ng/ml and 50-350 ng/g, respectively. The serum and epidermal values were significantly correlated (P less than 0.05). The drug progressively accumulated in the subcutis attaining a maximum value of 15,500 ng/g. After the treatment, etretinate disappeared from the epidermis within 1 week. By contrast, the drug remained in the subcutis for several months after cessation of treatment. The epidermal composition of endogenous retinoids changed during etretinate therapy as reflected in an increased ratio of 3-dehydroretinol to all-trans retinol.

Acitretin↗

Darier's disease and vitamin A. Concentrations of retinoids in serum and epidermis of untreated patients.

Blood samples and skin biopsy specimens from 13 male patients with Darier s disease (DD) and 11 healthy male controls were analyzed for carotene, retinol (vitamin A), dehydroretinol (vitamin A2), and retinol-binding protein (RBP). The serum carotene level was lower in the patients than in the controls, but the vitamin A and RBP levels did not differ from those of the controls regardless of the severity of the disease. The RBP could be visualized by immunofluorescence microscopy in the epidermis of both unaffected and lesional skin of patients with DD. In the epidermis of patients with DD (uninvolved and lesional), the carotene content was similar to that of the controls. The retinol content was probably higher than in the controls. By contrast, the dehydroretinol concentration was normal in the uninvolved skin but markedly higher than normal in the lesions, especially in the severe cases. The abnormal distribution of retinoids in DD may reflect localized disturbances of epidermal vitamin A metabolism rather than a defect in serum vitamin A transport.

Adolescent↗

Vitamin A in human skin: I. detection and identification of retinoids in normal epidermis.

In an attempt to identify vitamin A and derivatives (retinoids) specimens of breast skin epidermis (0.5 g) were homogenized, freeze-dried and extracted with chloroform/methanol. The evaporated extract was partitioned repeatedly between petroleum ether and a mixture of ethanol and pH-adjusted water. This yielded 3 fractions of partially purified retinoids. High-pressure liquid chromatography (HPLC) of these fractions revealed the presence of the following retinoids given in order to their abundance in the epidermis: retinyl acyl esters, retinol, 3-dehydroretinyl acyl esters and retinoic acid. Small amounts of other retinoids may also be present. In order to obtain quantitative data it was essential to add internal retinoid standards and to completely hydrolyze the skin in KOH-ethanol before extraction. The retinoids were deconjugated by this procedure but, with the exception of retinaldehyde, were otherwise unchanged. The recoveries of the endogenous retinoids at HPLC were identical to those of the internal standards. The technique was reproducible and could be applied to the analysis of nanograms of retinol and dehydroretinol in small (10-30 mg) skin specimens. The amounts of acidic retinoids were usually below the detection limit of the method (less than 10 ng/g) but the approach may be useful at the higher levels attained during retinoid therapy.

Chromatography, High Pressure Liquid↗

Vitamin A in human skin: II Concentrations of carotene, retinol and dehydroretinol in various components of normal skin.

Pro-vitamin A(beta-carotene) and the predominant forms of vitamin A in human skin (retinol and dehydroretinol) were analyzed in hydrolyzed specimens from 4 cadavers and 22 healthy subjects. Beta-carotene was identified in extracts of epidermis by its specific absorption spectrum. Vitamin A was determined by high-pressure liquid chromatography. The concentrations were related to the wet weight or protein content of the sample. The analysis of different skin compartments showed that the concentrations of the 3 constituents were usually related as follows: carotene greater than retinol greater than dehydroretinol. The concentrations were always higher in the epidermis than in the upper dermis. Skin surface lipids contained carotene and retinol but not in amounts sufficient to contribute to the higher epidermal values. Analysis of epidermal autopsies from 5 different skin areas (back, breast, arm, leg and foot) and of epidermal biopsies from the back of the healthy subjects showed that the interindividual differences were larger for carotene and dehydroretinol than for retinol, whereas the intraindividual variations were larger for retinol. The mean (+/- SD) concentrations of carotene, retinol and dehydroretinol in back skin epidermis of healthy subjects were 13 +/- 5, 1.7 +/- 0.4 and 0.4 +/- 0.2 microgram/g protein, respectively. No significant variations with age and sex were found.

Carotenoids↗

Skin content and plasma transport of vitamin A and beta-carotene in chronic renal failure.

The serum and cutaneous concentrations of beta-carotene and vitamin A and the serum concentrations of retinal-binding protein (RBP) and prealbumin were investigated in ten patients with chronic renal failure. The serum beta-carotene concentration was lower in the patients 1.3 +/- 0.7 mumol/l) than in the twenty-two healthy controls (2.4 +/- 0.9; P less than 0.01). The skin carotene concentration was also lower in patients than in controls (18.7 +/- 5.5 v. 24.6 +/- 9.9 nmol/g protein; P less than 0.05). By contrast, the patients' mean concentration of vitamin A in the skin was twice that of the healthy controls (11.0 +/- 4.8 v. 5.9 +/- 1.4 nmol/g protein; P less than 0.005) and in serum 3 times that of the controls (4.8 +/- 1.7 v. 1.8 +/- 0.3 mumol/l; P less than 0.001). The increase of serum vitamin A was accompanied by a rise in the RBP concentration, but the concentrations of vitamin A-esters and prealbumin remained in the normal range. It is suggested that vitamin A may accumulate in the skin as a result of an increased transfer of the vitamin by RBP. A possible relationship between high skin levels of vitamin A and uraemic skin symptoms is discussed.

Adult↗

Effects of etretinate (Ro 10-9359) on Darier's Disease.

The effect of the aromatic retinoid, etretinate, has been evaluated in 17 patients suffering from moderate to severe Darier's disease (DD). The erythema, hyperkeratosis and number of papules as well as the extension of the lesions were scored before and at regular intervals during treatment. In the first treatment period a daily dose of 50 mg was given until healing but no longer than 10 weeks. In the majority of patients the effect was very good with almost complete clearing in 6 patients. In patients with severe DD a reduction of the initial score by more than 50% was seen in 7 out of 8 patients. Isomorphic reactions developed in 6 of 17 patients and was the most important side effect. In patients with moderate disease the remission periods without treatment exceeded 4 weeks. 8 patients were treated intermittently with a lower dose up to 4 treatment periods. Equally good results were obtained. The treatment of choice in DD seems to be etretinate at an intermittent regime with low doses (less than or equal to 0.5 mg/kg).

Adolescent↗

Serum carotene, vitamin A, retinol-binding protein and lipoproteins before and after jejunoileal bypass surgery.

The plasma vitamin A and carotene transport in 45 obese patients was examined before and at various times after bypass surgery. The serum levels of lipoproteins, carotene, vitamin A and retinol-binding protein (RBP) were monitored and compared to those of healthy controls. LDL-cholesterol levels were decreased by 40 per cent (P less than 0.001) within the first year after surgery and remained low thereafter. The reduction of serum carotene (from a mean of 64 to 17 micrograms/dl) was rapid and constant. This change was observed already within 1-2 weeks post-surgery. The serum concentrations of carotene and LDL-cholesterol were highly correlated (r = 0.74). The concentrations of vitamin A and RBP were normal before the operation and remained so until 30 months after surgery, when slight reductions were observed compared to the control values [46 +/- 28 vs 66 +/- 11 micrograms/dl for vitamin A (P less than 0.01) and 32 +/- 8 vs 41 +/- 6 mg/l for RBP (P less than 0.01)]. No overt signs of vitamin A deficiency were observed. The mechanisms by which carotene (but not vitamin A) decreases so rapidly after bypass surgery cannot be explained by the decreased LDL levels.

Adult↗

Vitamin A in human semen.

Vitamin A concentration has been determined in human semen with and without hydrolysis by fluorometry and high performance liquid chromatography (HPLC). The vitamin A content of human spermatozoa is much lower than that reported for rabbit spermatozoa but approximately equal to that of bull spermatozoa.

Chromatography, High Pressure Liquid↗

The influence of 'Tigason' (Ro 10-9359) on the serum lipoproteins in man.

Eight patients with psoriasis or Darier's disease were studied during 1-3 months of 'Tigason' treatment (0.7-0.8 mg/kg body weight). The levels of triglycerides and cholesterol in whole serum and in different lipoprotein fractions were repeatedly determined. Before treatment all lipid values were within the normal range. During treatment the values changed gradually and five of the eight patients developed pathological VLDL triglyceride concentrations. A significant increase of VLDL cholesterol and a decrease in the HDL cholesterol was also noted. Until more information is available, prolonged treatment periods with 'Tigason' should perhaps be avoided, at least in high risk patients.

Cholesterol↗

The retinol-binding protein.

Vitamin A is transported from its storage site in the liver to the epithelial tissues by a carrier protein, the Retinol-binding protein (RBP). In plasma RBP forms a complex with thyroxine-binding prealbumin. The present article reviews available data on the RBP system. The complete primary structure of RBP has been determined. The plasma concentration of RBP is regulated by the vitamin A status so that in vitamin A deficiency RBP molecules are not secreted from the liver. RBP molecules interact with a cell membrane receptor, probably a protein component present on epithelial cells. Vitamin A is thereby delivered to the cells. The uptake of vitamin A by the cells causes a reduction of the affinity of RBP for prealbumin. The RBP molecules which no longer are able to interact efficiently with prealbumin are excreted through the kidney glomerulus and degraded.

Amino Acid Sequence↗

Vitamin A transporting plasma proteins and female sex hormones.

Retinol-binding protein, prealbumin, and sex steroid plasma levels have been estimated daily in four women during the course of a normal menstrual cycle and in three women during treatment with combined oral contraceptives. The retinol-binding protein level showed a bicyclic variation during the menstrual cycle, whereas for prealbumin no consistent pattern of variation was observed. Oral contraceptive therapy induced a significant increase of retinol-binding protein which was correlated with the increase of vitamin A. The increase was about 35% for the formulation containing synthetic estrogen as compared with 15% for the one with natural estrogen. In relation to retinol-binding protein, the plasma level of prealbumin showed a less rapid increase but the final increment after oral contraceptive therapy appeared to be of the same magnitude for both proteins.

Adult↗

Mechanisms for vitamin A transfer from blood to milk in rhesus monkeys.

In order to study vitamin transport during lactation tritium labeled vitamin A, attached to serum lipoproteins or retinol-binding protein (RBP), was injected intravenously into eight Rhesus monkeys. The turnover rate of vitamin A in plasma and its appearance in milk was quantitatively and qualitatively investigated. The turnover of plasma RBP-retinol, which was somewhat faster in lactating than in non-lactating animals, exceeded that of lipoprotein-vitamin A by a factor of three. Tritium--vitamin A appeared in milk mainly as retinylesters. The fractional rate of transfer was about 60% higher for vitamin bound to RBP than for other forms of plasma vitamin A. Consequently, about 90% of the vitamin A appearing in milk will normally be derived from the retinol-RBP complex. The importance of the lipoprotein-mediated transfer of vitamin A will probably increase during a high intake of the vitamin.

Animals↗