Shunji Imanaka

An open study of vitamin D3 treatment in psoriasis vulgaris.

Active forms of vitamin D3, 1α‐hydroxyvitamin D3 and 1α, 25‐dihydroxyvitamin D3, were administered in an open‐design study to 40 patients with psoriasis vulgaris in three ways: (i)to 17 patients 1α, hydroxyvitamin D3 was given orally at a dose of 1.0μ/day for 6 months, (2) to four patients 1α, 25‐dihydroxyvitamin D3 was given orally at a dose of 0.5μ/day for 6 months, and (3)19 patients were given 1α, 25‐dihydroxyvitamin D3, was applied topically at a concentration of 0.5μ/g of base for 8 weeks. Improvement was observed at the end of the individual study periods in 13 (76%) patients in Group I with a mean period of treatment (±SD) of 2.7 ± 0.6 months, in one patient in Group 2 at 3 months after the start of treatment, and in 16 (84%) patients in Group 3 when the chemical was applied for 3.3 ± 1.2 weeks. No side‐effects were observed in any of these trials. These data suggest that psoriasis may respond to active metabolites of vitamin D3 and that abnormalities in vitamin D metabolism or in responsiveness of the skin cells to active metabolites of vitamin D may be involved in the pathogenesis of this skin disease.

Topical administration of 1,25-dihydroxyvitamin D 3 for proriasis: Report of five cases

SummaryThe effects of topical administration of 1,25-dihydroxyvitamin D3, as 0.1 and 0.5 μg per g base, and control base applied to contralateral skin lesions in five patients with persistant psoriasis were compared. In all five, definite and in some cases remarkable improvement of the lesions was seen when 1,25-dihydroxyvitamin D3 at concentration of 0.5 μg per g base was applied for two to five weeks. No local or systemic toxicity was detected in any patient. Although the mechanism of the improvement is yet to be elucidated, these results show the possible effectiveness of topical 1,25-dihydroxyvitamin D3 on psoriatic skin lesions.

Effects of prostaglandins on the cytosolic free calcium concentration in vascular smooth muscle cells.

The effects of prostaglandin (PG) F2 alpha and 9,11-epithio-11,12-methanothromboxane A2 (STA2), a stable analogue of thromboxane A2, on the cytosolic free calcium concentration ([Ca2+]i) in vascular smooth muscle cells were studied with a new fluorescent Ca2+ indicator fura 2. PGF2 alpha and STA2, which are strong vasoconstrictors, caused rapid phasic and subsequent tonic increases in [Ca2+]i. PGF2 alpha caused dose-dependent elevation of [Ca2+]i not only in control solution but also in the calcium-free solution. A first stimulation with PGF2 alpha caused dose-dependent decrease in the response of [Ca2+]i to a second stimulation with PGF2 alpha. Pretreatment with 13-Azaprostanoic acid, a receptor level antagonist of thromboxane A2 inhibited the increase of [Ca2+]i induced by STA2. These results suggest that PGF2 alpha induces calcium mobilization followed by smooth muscle contraction through its specific receptors.

Effect of 1α-hydroxycholecalciferol on psoriasis vulgaris: a pilot study

SummaryWe carried out a clinical trial of 1α-hydroxycholecalciferol [1α(OH)D3] at a dose of 1.0 μg a day on 7 patients with psoriasis vulgaris. These patients had been treated by topical applications of corticosteroids before this study without improvement, and during the clinical trial, treatment of topical corticosteroids was continued on 6 of the 7 patients. Four of 7 patients showed complete remission and marked improvement and 2 additional patients showed minimal improvement of their skin lesions during and after the treatment with 1α(OH)D3. No adverse reactions were noted during the treatment period. The mechanism of the phenomenon we observed has yet to be elucidated. Controlled trials of large numbers of patients with psoriasis vulgaris treated with 1α(OH)D3 are under way.

Treatment of psoriasis vulgaris by oral administration of 1α-hydroxyvitamin D3—Open-design study

SummaryIn an open-design study 1α-hydroxyvitamin D3 was administered orally to 17 patiens with psoriasis vulgaris at a dose of 1.0 μg/day for 6 months. More than moderate improvement was observed in 13 (76 %) of the 17 patients from 2.7±0.6 months (mean±SD) after the start of treatment. No side effects of the treatment were observed. The mechanism of the effect of 1α-hydroxyvitamin D3 requires study, but these data suggest that its oral administration is effective for treatment of psoriasis vulgaris.

Inverse relation between severity of psoriasis and serum 1,25-dihydroxyvitamin D level

The serum levels of calcium, inorganic phosphate, parathyroid hormone, calcitonin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 34 patients with psoriasis vulgaris and compared with the severity of skin lesions. Severity of psoriasis was evaluated by three indices, the area-severity index (ASI), the area index (AI) and the severity index (SI), determined as the product of the area and severity, the area, and the severity of the individual skin lesions, respectively. The mean basal levels of these serum parameters were within the normal range. ASI and SI showed significant inverse correlations (r = -0.387, P less than 0.05 and r = -0.638, P less than 0.01, respectively) with the serum level of 1,25-dihydroxyvitamin D, but not with any other serum parameters, but AI was not correlated with any of these serum parameters. These data suggest that psoriatic patients are not deficient in 1,25-dihydroxyvitamin D, but that development of this skin disease may be related to a slightly decreased level of active metabolites of vitamin D or abnormalities in the responsiveness of the skin cells to them.

Treatment of Psoriasis Vulgaris with Oral 1α,25‐Dihydroxyvitamin D3

Psoriasis is a common inflammatory skin disease, but its pathogenesis is unknown. This paper presents 2 cases of psoriasis vulgaris in which the skin lesions were improved for 3 months and more after the start of oral treatment with 1α,25‐dihydroxyvitamin D3 at a dose of 0.5 μg/day. The circulating levels of calcium, inorganic phosphate, 25‐hydroxyvitamin D, 1α,25‐dihydroxyvitamin D, parathyroid hormone and calcitonin were within normal ranges before and after the start of treatment. These findings suggest that 1α,25‐dihydroxyvitamin D3 has a beneficial effect on psoriatic skin lesions. It probably has a direct effect on enhancing epidermal cell differentiation.

Serum phosphate, parathyroid hormone and vitamin D metabolites in patients with chronic renal failure: effect of aluminum hydroxide administration.

Patients with chronic renal failure showed the existence of phosphate retention, secondary hyperparathyroidism, and reduced production of 1,25-(OH)2D. In order to determine the effect of correction of hyperphosphatemia on secondary hyperparathyroidism and vitamin D metabolism in those patients, 7 nondialyzed patients with chronic renal failure were treated with large doses of A1(OH)3 (15-18 g/day) to correct their high levels of serum phosphate. After treatment with A1(OH)3, serum phosphate fell significantly (p less than 0.005) from 6.3 +/- 1.3 (mean +/- SD) to 3.7 +/- 0.5 mg/dl. Serum parathyroid hormone decreased significantly (p less than 0.02) from 2.87 +/- 1.64 to 1.85 +/- 1.26 ngEq/ml. Serum 1,25-(OH)2D was low compared to the normal mean level before A1(OH)3 administration and decreased significantly (p greater than 0.02) from 19.4 +/- 6.1 to 11.4 +/- 4.3 pg/ml after the treatment. Aluminum levels increased significantly (p greater than 0.02) from 1.7 +/- 1.0 to 3.6 +/- 1.5 micrograms/dl. Serum calcium, calcitonin, and 25-(OH)D showed no significant change. Our data suggested that the suppression of secondary hyperparathyroidism by A1(OH)3 treatment results in a decrease of the 1,25-(OH)2D level in patients with chronic renal failure, even though their hyperphosphatemia has been corrected. We speculate that aluminum loading might play a role in diminishing the secretion of parathyroid hormone and the production of 1,25-(OH)2D in humans.

Comparison of renal responses to synthetic human PTH(1-34) administration in normal young and elderly male subjects

SummaryA parathyroid hormone (PTH) loading test with synthetic human PTH(1–34) was performed in 7 young and 6 elderly normal males. The elderly subjects had significantly higher mean basal levels of serum PTH than the young subjects (0.262±0.035(SE) vs 0.097±0.012 ng Eq/ml,P<0.001). When human PTH(1–34) at a dose of 100 U was administered to these subjects, the mean increases in urinary excretions of adenosine cyclic 3′, 5′-monophosphate(cAMP) and inorganic phosphorus (Pi), expressed as increases in absolute amounts per unit time, were significantly lower in the elderly subjects. (3.65±1.02 vs 7.41±1.05 μmol/h,P<0.05 for cAMP and 14.7±6.3 vs 41.8±8.6 mg/2h,P<0.05 for Pi) and an inverse correlation was found between the serum PTH levels and the increases in urinary cAMP excretion (μmol/hr; r=−0.63,P<0.05). However, when corrected for the glomerular filtration rate (GFR) and the units of PTH administered per kg body weight, the increases were not significantly different in the two groups (elderly 52.1±7.5 vs young 60.0±19.2 nmol·kg/100 ml GFR·U·h for cAMP and 0.315±0.061 vs 0.186±0.044 mg·kg/100 ml GFR·U·2 h respectively for Pi). These results indicated that the decreased response of the kidney to PTH in elderly subjects can be explained mainly by the decreased functional mass of the kidney, possibly with some contribution of down-regulation of PTH receptors owing to increase in the blood level of endogenous PTH in elderly subjects. Further investigations are needed to ascertain why there was decreased response of the kidney to PTH in elderly people.

Participation of Decreased Serum CholesteryI Ester Transfer Activity, Independent of Increased Serum Lipoprotein(a), in Angina Pectoris in Normolipemic Elderly Subjects

The cholesteryl ester transfer activity (CETA) is a measurement of the transfer of cholesteryl ester from HDL to VLDL, LDL or peripheral cells. Its role in the development of early coronary heart disease is not clear. In the present study, serum levels of CETA, lipoprotein(a) [Lp(a)] and other lipid-related factors were compared in 10 normal young subjects, 28 healthy elderly subjects and 14 normolipemic elderly patients with angina pectoris. Compared to the young normals and healthy elderly subjects, the elderly patients with angina pectoris showed significantly decreased mean serum CETA levels, and significantly increased mean serum levels of Lp(a) and apoprotein B. These results may indicate that decreased serum values of CETA participate in the development of angina pectoris in normolipemic elderly patients.