Search PubMed⌕ Search

Biomedical subjects

A Vahlquist

Publications and source records attributed to A Vahlquist.

At least 91 records · Page 5Linked to original sources
PubMed1986

Oral isotretinoin (13-cis-retinoic acid) therapy in severe acne: drug and vitamin A concentrations in serum and skin.

The disposition of oral isotretinoin to the skin and the effects of the drug on the vitamin A levels in serum and skin were studied in 17 patients with nodulocystic acne. All patients received 0.5 mg/kg/day for 3 months and 8 patients continued treatment with 0.75 mg/kg/day for another 3 months. The parent drug, the major metabolite (4-oxo-isotretinoin), and 2 natural retinoids (retinol and dehydroretinol) were monitored in serum and biopsies of uninvolved skin, using adsorption high-pressure liquid chromatography. During the initial 3 months of treatment the mean isotretinoin level in the serum was 145 ng/ml and in the epidermis 73 ng/g. The corresponding values for 4-oxo-isotretinoin were 615 and 113 ng/g, respectively. Even at the highest dosage there was no progressive accumulation of isotretinoin in serum, epidermis, or subcutis. After discontinuation of therapy the drug disappeared from both serum and skin within 2-4 weeks. The serum transport of vitamin A, monitored by the concentrations of retinol, retinol-binding protein, and prealbumin (transthyretin), was not affected by the treatment. By contrast, the retinol level in the epidermis increased by an average of 53% (p less than 0.01) and the dehydroretinol level decreased by 79% (p less than 0.001) as a result of 3 months of treatment. Both changes were reversible. The results suggest that isotretinoin therapy interferes with the endogenous vitamin A metabolism in the skin.

Acne Vulgaris↗
PubMed1986

Changes in laboratory variables induced by isotretinoin treatment of acne.

During a trial of isotretinoin (0.5 mg/kg body weight/day for 3 months) in 90 patients with severe acne, the leucocyte (WBC) count, and particularly the number of neutrophils, decreased significantly. In patients with a good response the mean WBC count fell by 24% and the neutrophils by 33%, whereas in those with a poor response these variables decreased by 8% and 14%, respectively. The serum ALAT, ASAT, cholesterol and triglyceride levels increased significantly. Patients with a poor response (n = 35) received a higher dosage (0.75 mg/kg) for an additional 3 months, and during this period there was a further decrease in the WBC and neutrophil counts and an increase in the triglyceride level. In the other patients, who initially responded well, the dosage was decreased to 0.1 or 0 mg/kg during the second 3-month period, which resulted in reversion of the laboratory variables to the pre-treatment levels. The observed changes were clearly both dose-dependent and reversible.

Acne Vulgaris↗
PubMed1986

Tissue distribution of aromatic retinoid (etretinate) in three autopsy cases: drug accumulation in adrenals and fat.

The problematic storage of etretinate in fat during chronic etretinate therapy prompted us to search for other "high-affinity" tissues in 3 patients studied at autopsy. Specimens from eleven organs were analysed for etretinate and its main metabolite, etretin, by high-performance liquid chromatography. The results confirmed an accumulation of etretinate in fat and to a lesser degree in liver. High levels of etretinate were also found in the adrenals and, in one case, this value exceeded that of the fat tissue. Low levels were observed in several other organs, notably the kidneys, brain and testis. With the possible exception of liver and gut, the metabolite did not accumulate in any particular organ. Although the available data is still limited, the risk that the accumulation of etretinate in the adrenals may adversely affect adrenal function must be examined.

Acitretin↗
PubMed1985

Psoriasis and vitamin A. Plasma transport and skin content of retinol, dehydroretinol and carotenoids in adult patients versus healthy controls.

The vitamin-A status of 107 patients with psoriasis and 37 healthy controls was investigated. The mean serum level of retinol-binding protein (RBP) was normal in the 79 patients with chronic plaque psoriasis covering 25% or less of the skin surface. In the 28 patients with more extensive plaque lesions or pustular/erythrodermic psoriasis, the mean serum RBP level was significantly lower than in the controls (P less than 0.05). The cutaneous concentrations of retinol (vitamin A1), dehydroretinol (vitamin A2) and carotenoids were measured in extracts of saponified shave-biopsy specimens of uninvolved and involved skin from 33 patients with plaque psoriasis. Their retinol values did not differ significantly from those found in control skin (mean, 252 ng/g), whereas the carotenoid levels in both uninvolved and involved skin were 25%-50% lower. In contrast, the dehydroretinol concentration was higher in the patients' involved skin (mean, 237 ng/g) than in their uninvolved skin (94 ng/g) and healthy control skin (70 ng/g; P less than 0.01). Although the origin of increased dehydroretinol levels in involved psoriatic skin is unknown, similar increments were observed in control epidermis in which proliferation had been induced by tape stripping. In 7 patients treated with oral etretinate (aromatic retinoid) for 2-3 weeks, the median retinol and dehydroretinol levels in involved skin increased by 107% and 212%, respectively; the vitamin-A concentrations in uninvolved skin did not change significantly. Oral treatment with beta-carotene/canthaxanthin raised the median carotenoid levels in uninvolved and involved skin by 170% and 610%, respectively, without significantly affecting the vitamin-A composition.

Adolescent↗
PubMed1985

Biosynthesis of 3-dehydroretinol (vitamin A2) from all-trans-retinol (vitamin A1) in human epidermis.

Since the origin of 3-dehydroretinol in epidermis is unknown, we have investigated the possible conversion of all-trans-retinol to 3-dehydroretinol by organ cultured keratome slices (0.3 mm) of human breast skin. [3H]Retinol bound to retinol-binding protein (RBP) was incubated for 24 h with the tissue sample, which was then extracted and analyzed by high-performance liquid chromatography. Radioactive material that comigrated with authentic 3-dehydroretinol was purified to homogeneity. The identity of this material was established by treatment with HCl which resulted in a typical formation of the anhydro form of 3-dehydroretinol. 3-[3H]Dehydroretinol could not be detected in the incubation medium and was not found in the skin when the sample was heat-inactivated before incubation. The tissue production of 3-[3H]dehydroretinol from [3H]retinol continued when the tracer was removed from the medium, attaining a maximum value of 25% of the retinol value at 50 h. It is suggested that epidermal 3-dehydroretinol in vivo originates from serum retinol delivered to the keratinocytes by RBP.

Chromatography, High Pressure Liquid↗
PubMed1985

A sequential comparison of etretinate (Tigason) and isotretinoin (Roaccutane) with special regard to their effects on serum lipoproteins.

Etretinate and isotretinoin were compared with respect to their clinical effects and changes in serum lipoprotein concentrations. Sixteen patients with hyperkeratotic and pustular disorders of hands and feet (mainly palmoplantar pustulosis) underwent a double-blind cross-over study. The daily doses of etretinate and isotretinoin were 50 and 40 mg, respectively. Each drug was given for 2 months with a 2-month intermission. The clinical score was reduced both by isotretinoin (P less than 0.05) and etretinate (P less than 0.001). Both drugs affected the lipoprotein concentrations. Isotretinoin increased the cholesterol concentration in low-density lipoprotein (LDL) by 20% and the triglyceride concentration in very low-density lipoprotein (VLDL) by 35%, but decreased the high-density lipoprotein cholesterol by 12%. Etretinate elevated LDL-cholesterol by 10%. These changes had reverted to normal 8 weeks after the end of treatment. The data suggest that in the diseases studied, etretinate is preferable to isotretinoin with regard to both clinical effect and serum lipid side-effects.

Adult↗
PubMed1985

Vitamin A in skin and serum--studies of acne vulgaris, atopic dermatitis, ichthyosis vulgaris and lichen planus.

The concentrations of vitamin A and total carotenoids were measured in serum and skin of 61 patients with acne vulgaris, atopic dermatitis, ichthyosis vulgaris or lichen planus, and compared with those in 37 healthy subjects. The mean serum concentrations of retinol and retinol-binding protein were significantly decreased in patients with acne (P less than 0.01) and slightly increased in those with ichthyosis (P less than 0.05), but were otherwise normal. Serum carotenoid levels did not differ between patients and controls. Superficial shave biopsies from both involved and uninvolved skin were examined for the presence of retinol (vitamin A1), dehydroretinol (vitamin A2) and total carotenoids. The mean retinol concentration was increased in lichen planus lesions (P less than 0.05) and decreased in both acne skin (involved and uninvolved) and in lesions of atopic dermatitis (P less than 0.05). The mean dehydroretinol concentration was markedly increased in lesions of atopic dermatitis and lichen planus (P less than 0.01). No consistent abnormalities were found in skin of patients with ichthyosis vulgaris. The mean carotenoid concentration in the patients' skin did not differ significantly from that in the controls. The reduced retinol level in the skin of acne patients is probably explained by diminished supply of vitamin A from the blood. The abnormal ratio of retinol to dehydroretinol in lesions of lichen planus and atopic dermatitis is possibly due to changes in cutaneous vitamin A metabolism associated with epidermal hyperproliferation and inflammation.

Acne Vulgaris↗
PubMed1985

Vitamin A losses during continuous ambulatory peritoneal dialysis.

Since continuous ambulatory peritoneal dialysis (CAPD) causes losses of certain plasma proteins and their ligands, we examined the serum concentrations of vitamin A and retinol-binding protein (RBP), as well as the concentrations of vitamin A in the skin and dialysis fluid from 32 patients on CAPD over a period of 1-30 months (mean 7.5). The mean values of vitamin A and RBP in serum were 2-4 times higher than those in the healthy controls; a consistent finding in patients with chronic renal failure. Similarly, the vitamin A concentrations in skin were elevated in the CAPD patients (p less than 0.01). The vitamin A content of the dialysate (mean 1.4 mumol/24 h), which correlated significantly with the serum vitamin A concentration (r = 0.67), was constant during CAPD treatment. RBP was present in the dialysate and its concentration closely correlated with that of vitamin A (r = 0.95), indicating that the transperitoneal diffusion involved retinol-RBP. This conclusion was supported by calculations of clearance rates. Despite the considerable losses of vitamin A in CAPD fluid, the patients' vitamin A concentrations in serum and skin remained elevated. Whether extended CAPD treatment (greater than 30 months) may eventually affect the vitamin A situation in chronic renal failure warrants further observations.

Biological Transport, Active↗
PubMed1985

Differential hepatotoxicity of two oral retinoids (etretinate and isotretinoin) in a patient with palmoplantar psoriasis.

A 64-year-old woman developed biopsy-proven hepatitis during oral treatment of severe pustular psoriasis of palms and soles with an aromatic retinoid, etretinate. The elevations in hepatic enzyme levels reappeared when etretinate was reinstituted 18 months later. Analysis of serum and subcutis showed normal therapeutic concentrations of the drug. Isotretinoin therapy, although apparently devoid of hepatotoxicity, was clinically only marginally effective. Evidence compiled from the literature suggests that etretinate-hepatitis is a drug-specific reaction.

Chemical and Drug Induced Liver Injury↗
PubMed1985

Serum prealbumin and retinol-binding protein in the prealbumin-related senile and familial forms of systemic amyloidosis.

In a series of 13 elderly patients with proven prealbumin-related senile systemic amyloidosis (SSA), depressed serum prealbumin values (110.7 +/- 14.1 micrograms/ml) were found as compared to an age-matched control group (175.1 +/- 20.3 micrograms/ml). As expected, there was a significant correlation between serum prealbumin and serum retinol-binding proteins in both groups of patients. Patients with reactive amyloid protein AA amyloidosis had slightly depressed serum prealbumin concentrations, whereas patients with prealbumin-related familial amyloidosis of Swedish type had prealbumin values within normal limits. Since the serum levels of the acute phase reactants, haptoglobin and amyloid-related serum protein AA, were higher in the group of patients with reactive amyloidosis than in patients with SSA, the depression of the prealbumin levels in SSA is not a result of inflammation. Since SSA is known to contain prealbumin, it is possible that a disturbed prealbumin metabolism in old age results in low prealbumin serum values and deposition of amyloid.

Adult↗
PubMed1984

Vitamin A uptake by human skin in vitro.

Results are presented establishing that epidermis accumulates vitamin A from serum retinol-binding protein (RBP). Strips of human breast skin (0.2-0.3-mm thick) were incubated in a serum-free medium. From the rate of glucose oxidation, the tissue was viable for at least 48 h at 32 degrees C in 5% CO2 air. [3H]-Retinol-RBP (10(-6) M) was added to the medium for 1-24 h, after which epidermis and dermis were split and separately extracted with hexane after saponification. [3H]-Retinol was isolated by high performance liquid chromatography (HPLC). Epidermis had 6-7 times higher affinity for [3H]-retinol than dermis. The uptake could be saturated by substrate and was inhibited with unlabelled retinol-RBP but not with serum albumin. Furthermore, although the uptake was temperature-dependent, it seemed independent of cellular energy production. The epidermal accumulation of [3H]-retinol was reduced by the filtering action of dermis. On the basis of these observations, an in vitro model for the delivery of vitamin A to human skin has been proposed.

Cells, Cultured↗
PubMed1984

UV irradiation and cutaneous vitamin A: an experimental study in rabbit and human skin.

The effect of UV irradiation on the concentration of cutaneous retinoids (retinol and 3-dehydroretinol) in rabbit skin in vivo and in human skin in vitro was investigated. Irradiation with 4 different narrow-wavelength bands produced dose-dependent reductions of retinol in epidermis and dermis. The maximal effect was obtained at 334 nm, a wavelength which coincides with the absorption maximum for retinol in organic solutions. 3-Dehydroretinol was not reduced to the same extent as was retinol. In human skin the photodecomposition of retinol was most extensive in epidermis and progressively less so in dermis, presumably reflecting the extent to which 334 nm radiation penetrates the tissue. The regeneration of cutaneous retinol took over a week in the rabbit. The nutritional and biologic implications of the UV-induced reduction of cutaneous retinol remain to be established.

Animals↗
PubMed1984

UV treatment of uraemic pruritus reduces the vitamin A content of the skin.

The effect of phototherapy on uraemic pruritus and vitamin A content in serum and epidermis was investigated in ten patients with chronic renal failure. The patients and five healthy controls were given repeated whole-body irradiation of UV-A + UV-B (total dose 7.9 + 1.3 J cm-2). Serum and skin samples were obtained before and after the treatment. Serum samples were analysed for retinol, retinol-binding protein and carotene and epidermis samples for retinol, 3-dehydroretinol and carotene. Before treatment, the retinol concentrations in serum and epidermis were higher in patients than in controls. The treatment, which relieved seven patients of pruritus, reduced the epidermal retinol from 11.6 +/- 4.5 to 7.0 +/- 3.8 nmol g-1 protein (P less than 0.02). A similar reduction occurred in the controls (4.5 +/- 1.0 v. 1.7 +/- 1.0, P less than 0.01). No changes of epidermal 3-dehydroretinol, carotene or the serum parameters occurred in either patients or controls. The putative relationship between uraemic pruritus and hypervitaminosis A and the response of this condition to UV therapy is discussed.

Adult↗
PubMed1984

Vitamin A nutrition in the human foetus. A comparison of Sweden and Ethiopia.

The accumulation of vitamin A during foetal development was investigated post mortem in foetuses and newborn infants of well-defined socio-economic groups of Swedish and Ethiopian women. The median vitamin A concentration in the liver was 37.0 micrograms/g in the Swedish foetuses (n = 39) and 9.1 micrograms/g in the Ethiopian ones (n = 49) (p less than 0.001). The liver vitamin A concentration in the Swedish foetuses increased exponentially during the second and third trimesters of pregnancy. This trend was not evident in the Ethiopian material. The mean serum concentration of retinol-binding protein was only slightly lower in the healthy Ethiopian newborns (18.6 mg/l; n = 70.) than in the Swedish newborns. This finding suggests that vitamin A is retained i the foetal circulation in preference to storage, much like the situation in a vitamin A deficiency state in the adult.

Adolescent↗
PubMed1984

Vitamin A transfer to the fetus and to the amniotic fluid in rhesus monkey (Macaca mulatta).

The mechanisms of the fetal transmission of vitamin A were investigated by injecting 125I-retinol-binding protein (RBP), 131I-prealbumin and 3H-retinol-RBP in 9 pregnant rhesus monkeys. Samples of blood, amniotic fluid, and when needed fetal liver and kidney were collected after 2.5-48 h. 125I-RBP and 131I-prealbumin were detected in fetal plasma and amniotic fluid already in the first samplings. The specific radioactivity of fetal RBP increased during the first 25 h but never exceeded 13% of the maternal value. This is presumably due to concurrent synthesis of RBP (and prealbumin) by the fetus. The maximum specific activity of 125I-RBP in amniotic fluid was 70% of the maternal value indicating that the protein was predominantly derived from the mother. 3H-retinol was more readily transmitted to fetal plasma than RBP. A significant portion of the 3H activity was found in the lipoproteins suggesting that some retinol enters the fetal circulation by other routes than those involving transmission of RBP. The high specific activity of retinol in the fetal kidney implicates its direct involvement in the turnover of transmitted vitamin A. Quantitatively, however, the accumulation of vitamin A activity was largest in the fetal liver.

Amniotic Fluid↗