1-alpha-24-dihydroxyvitamin-d3 and Psoriasis

Topics: Adult; Antibodies, Monoclonal; Calcitriol; Dermatologic Agents; Dihydroxycholecalciferols; Fumarates; Humans; Psoriasis; Ultraviolet Therapy; Vitamins

Several topical treatments such as ointments, keratolytics, dithranol, tar, corticosteroids and Vitamin D3 analogues are commonly used in the treatment of mild and/or moderate psoriasis. These treatments can be associated with a variety of local and systemic side effects, as well as to very often unsatisfactory results. The purpose of this critical review of the literature is to evaluate the efficacy and tolerability of the synthesis of new analogues of the Vitamin D3 Tacalcitol, which is formulated in ointment form at a concentration of 4 microg/g, for the treatment of mild and/or moderate psoriasis (involvement of <20% of the surface of the skin) and to evaluate whether this drug can be used in the treatment of other skin conditions. Based on existing data in the literature, Tacalcitol is an effective drug for the topical treatment of psoriasis and is also able to ensure that the effects last over time, even after treatment has stopped. Tacalcitol is also well tolerated because the onset of side effects, such as local irritation, pruriginous or burning sensations, were reported in only a small percentage of the subjects who were treated. Lastly, the marked regulatory effects it has on the proliferation and differentiation of keratinocytes, as well as on the immunocompetent cells, has led to suggestions that Tacalcitol may be used in other keratinisation disorders and in some hyperproliferative skin diseases. Evaluation of the effective indications to use in these conditions still requires further data confirming its effectiveness, opening the way to wider use of this molecule in dermatology.

Topics: Adult; Aged; Clinical Trials as Topic; Dermatologic Agents; Dihydroxycholecalciferols; Double-Blind Method; Female; Humans; Keratinocytes; Male; Multicenter Studies as Topic; Ointments; Phototherapy; Psoriasis; PUVA Therapy; Skin Diseases; Time Factors; Vitiligo

Mild to moderate psoriasis is a disease that can often be treated with topical medications. The diversity of topical therapies and their disparate side effects complicates treatment planning. Our purpose is to compare the rates of adverse events associated with different topical psoriasis treatments. A review of medical literature from 1996 to March, 2002 was conducted using guidelines set by QUORUM statement criteria. In monotherapy studies, corticosteriods caused fewer adverse reactions compared to vitamin D analogues and tazarotene. In combination studies adverse event rates were higher than in monotherapy studies, except for the combination of topical steroid and calcipotriene which decreased irritation. Irritant contact dermatitis was the main side effect with vitamin D analogues, tazarotene, dithranol or coal tar, while side effects of topical corticosteriods included headache, viral infection and skin atrophy. Topical agents for psoriasis are usually well-tolerated without severe side effects. Formulating a patient's medication regimen should take into account the needs for short-term management and long-term control of psoriasis. Since clearance is not a realistic expectation, reasonable goals should be set as excessive use of topical treatments may increase the risk of both cutaneous and systemic side effects.

Topics: Administration, Topical; Adrenal Cortex Hormones; Anthralin; Calcitriol; Coal Tar; Dermatologic Agents; Dihydroxycholecalciferols; Drug Therapy, Combination; Erythema; Humans; Nicotinic Acids; Pain; Pruritus; Psoriasis; Vitamin D

Within the past decade it has been shown that psoriasis can be treated topically with analogs of vitamin-D3. Impaired differentiation and increased proliferation of keratinocytes are key features in psoriatic lesions together with a local activation of T lymphocytes. Evidence has accumulated showing that analogs of vitamin D3 increase differentiation and inhibit proliferation of keratinocytes. Therefore, analogs of vitamin D3 have been investigated in a number of trials showing improvement of psoriasis. It has been shown that vitamin D analogs are better than their vehicle and show the same potency as potent topical steroids. However, vitamin D analogs have been proven efficacious and without side effects also when used on long term basis. Vitamin D analogs can be used both as monotherapy and in combination topical steroids, UVB, PUVA, retinoids and cysclosporine. The vitamin D3 analog calcipotriol has been investigated in most detail and is available as an ointment, a creme and as a scalp solutation. From clinical studies involving thousands of patients, it can be concluded that calcipotriol is efficacious, safe, well tolerated and can be used on a long term basis. Other analogs are available, however, these analogs have not been studied in greater details yet.

Topics: Calcitriol; Cholecalciferol; Dermatologic Agents; Dihydroxycholecalciferols; Drug Therapy, Combination; Humans; Psoriasis

Multiple studies have shown the benefit of topical tacalcitol treatment for chronic plaque psoriasis. Tacalcitol ointment 4 micrograms/g is efficacious and well tolerated as both monotherapy and in combination with other treatments such as ultraviolet light therapy. It can be used all over the body including the face and scalp.

Topics: Administration, Topical; Anti-Inflammatory Agents; Dermatologic Agents; Dihydroxycholecalciferols; Drug Therapy, Combination; Humans; Multicenter Studies as Topic; Product Surveillance, Postmarketing; Psoriasis; PUVA Therapy; Randomized Controlled Trials as Topic

Vitamin D3 analogs interfere with various aspects of epidermal growth, inflammation, and cellular differentiation. Most data are derived from in vitro studies. In the present review, the in vivo effects of vitamin D3 analogues on the psoriatic plaque are discussed. Calcipotriol, tacalcitol, and calcitriol in ointment modulate aspects of epidermal growth, differentiation, and inflammation. Immunohistochemical studies suggest that the inflammatory changes might be more expressed after treatment with calcitriol and tacalcitol. Flow cytometric quantification of the percentage of cells in SG2M phase and of keratin 10-positive cells revealed that calcipotriol reduced both indices significantly during treatment of psoriatic plaques. Flow cytometric analysis of epidermal cell suspensions using triple labeling for epidermal proliferation, expression of keratin 10, and vimentin permits a quantitative assessment of DNA synthesis selectively in the basal cells of the epidermis, an estimation of the distribution of the basal and suprabasal compartments, and a quantification of the distribution of mesenchymal and nonmesenchymal cells. Using this approach, the interference of tacalcitol with growth control of basal cells was demonstrated. Remarkably, recompartmentalization of basal and suprabasal cells and mesenchymal and nonmesenchymal cells proved to be inconspicuous during this treatment.

Topics: Calcitriol; Dihydroxycholecalciferols; Epidermis; Flow Cytometry; Humans; Immunohistochemistry; Inflammation; Psoriasis

A combination of calcipotriol and narrow-band ultraviolet B (NBUVB) has been shown to have a superior efficacy as compared to NBUVB alone in psoriasis. Very few studies have been performed using the combination of NBUVB with tacalcitol, a comparatively newer Vitamin D analogue.. Comparison of the efficacy and safety of topical tacalcitol in combination with NBUVB versus NBUVB alone in psoriasis.. Thirty patients with plaque psoriasis were taken up for a 12 week, open-label, right-left intra-individual clinical trial. NBUVB phototherapy was given thrice weekly. The target lesions on one side were treated topically with tacalcitol ointment once daily, while no topical treatment was given on the other side. Efficacy was assessed by target plaque scoring.. Better improvement in plaques was seen with combination therapy as compared to NBUVB monotherapy, with a statistically significant difference from 2 to 8 weeks. The combination led to an earlier clearance of plaques and a better maintenance of the response than NBUVB alone. The number of treatment sessions and cumulative NBUVB doses were significantly lower in the tacalcitol-treated group.. Topical tacalcitol enhances the therapeutic effects of NBUVB therapy and exerts a UVB-sparing effect, without increasing the incidence of adverse effects.

Topics: Administration, Topical; Adult; Dermatologic Agents; Dihydroxycholecalciferols; Female; Humans; Middle Aged; Ointments; Photochemotherapy; Psoriasis; Treatment Outcome; Ultraviolet Therapy; Young Adult

Topics: Adult; Aged; Aged, 80 and over; Calcitriol; Cholecalciferol; Dermatologic Agents; Dihydroxycholecalciferols; Female; Humans; Male; Middle Aged; Psoriasis; Treatment Outcome

To establish the efficacy and safety of once daily treatment of Daivobet®/Dovobet® gel in patients with psoriasis vulgaris, relative to tacalcitol ointment and the gel vehicle alone.. 458 patients with at least moderately severe disease were randomized in 3 treatment arms for an 8-week period. Treatment was investigator blinded, and treatment success was defined as patients with an Investigator's Global Assessment of 'clear' or 'almost clear' at week 8.. The proportion of patients who were 'clear or almost clear' was significantly higher in the 2-compound gel group (39.9%) compared with 17.9% in the tacalcitol group and 5.5% in the gel vehicle group: p < 0.001 in both comparisons. The proportion of patients with at least 1 adverse drug reaction was significantly lower in the 2-compound gel group compared to the other 2 treatment groups.. Once-a-day treatment with the 2-compound Daivobet/Dovobet gel is a safe and efficacious therapeutic regimen for individuals with psoriasis on the body.

Topics: Adult; Betamethasone; Calcitriol; Dermatologic Agents; Dihydroxycholecalciferols; Drug Combinations; Female; Gels; Humans; Male; Middle Aged; Ointment Bases; Pharmaceutical Vehicles; Psoriasis; Severity of Illness Index; Treatment Outcome

This pilot randomized intra-patient side to side trial was designed to assess the antipsoriatic efficacy, safety and tolerability of once daily versus the separate application of a vitamin D3 analogue and a powerful corticosteroid.. Twenty patients with plaque type psoriasis were enrolled. Two similar symmetrical lesions were randomized to be treated with an application of an ointment containing calcipotriol 50 µg/g plus betamethasone dipropionate 0.5 mg/g once daily or the application of budesonide 0.25 mg/g cream in the morning and tacalcitol 4 µg/g ointment in the evening.. Eighteen patients completed the study. Both treatments proved to be effective but budesonide cream and tacalcitol ointment gave a faster improvement of lesions and itching relief at t1 and were better tolerated.. The separate daily regimen may represent a suitable treatment option for patients who need a faster improvement and a better moisturizing activity. Further studies which compare the efficacy and safety of these regimens need to be developed.

Topics: Administration, Cutaneous; Adult; Aged; Betamethasone; Budesonide; Calcitriol; Dermatologic Agents; Dihydroxycholecalciferols; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Ointments; Pruritus; Psoriasis; Time Factors; Young Adult

Facial psoriasis gives rise to considerable concern because of associated cosmetic problems and psychosocial distress. It requires a treatment approach other than topical corticosteroids, which bear a risk of cutaneous adverse reactions. Recently, topical tacalcitol has been shown to be effective in psoriasis.. The aim of this open-label single-centre study is to investigate the efficacy and safety of high-concentration (20 μg g⁻¹) ) tacalcitol ointment (Bonalfa-high(®) , Teijin Pharma, Tokyo, Japan) in patients with facial psoriasis and to evaluate clinical response according to the distribution of facial psoriatic lesions.. Thirty-seven patients were enrolled to this clinical trial. Tacalcitol 20 μg g⁻¹ ointment was applied once daily to psoriatic lesions of the face over an 8-week period. Patients were also categorized into three subtypes according to facial lesion distribution. Efficacy was evaluated by the facial Psoriasis Area and Severity Index (facial PASI) and the Physician's Global Assessment (PGA) score at weeks 2, 4 and 8. The Subjective Global Assessment (SGA) was also determined at the end of the study.. Thirty-three patients completed the clinical trial. Mean facial PASI of 33 patients at baseline was 9·58 and after 8 weeks of treatment the mean facial PASI decreased significantly to 3·88. By using PGA, patients showed the following responses to treatment: clearance (n = 1); excellent (6); good (16); fair (4); slight (5); no change (1). The response rate among the three facial psoriasis types showed no difference. Using the SGA, 27 (82%) of the patients presented excellent (15%) or good (67%) effect with tacalcitol 20 μg g⁻¹ ointment. No serious adverse reactions were observed.. This is the first clinical study reporting a relevant therapeutic effect and favourable safety profile of tacalcitol 20 μg g⁻¹ ointment in facial psoriasis. These results suggest that tacalcitol 20 μg g⁻¹ ointment can be used as the first-line treatment in patients with facial psoriasis.

Topics: Adult; Aged; Dermatologic Agents; Dihydroxycholecalciferols; Facial Dermatoses; Female; Humans; Male; Middle Aged; Ointments; Prospective Studies; Psoriasis; Severity of Illness Index; Young Adult

Tacalcitol is a vitamin D analog with proven efficacy for the topical treatment of psoriasis, but to date it has not been tested in psoriasis of the nail. However, successful treatment has been reported with other vitamin D derivatives such as topical calcipotriol, and topical calcitriol in one study. The present study aimed to assess the efficacy and tolerability of topical tacalcitol in the treatment of nail psoriasis in a sample of 15 patients over a 6-month period. Treatment with tacalcitol ointment may be useful to treat nail psoriasis as it achieves a significant improvement in all nail parameters, both of the matrix and of the bed.

Topics: Administration, Topical; Dermatologic Agents; Dihydroxycholecalciferols; Female; Follow-Up Studies; Humans; Male; Nail Diseases; Ointments; Psoriasis; Treatment Outcome

Three high-concentration vitamin D3 ointments are currently available in Japan for the treatment of psoriasis. The aim of the present study is to investigate the efficacy of high-concentration tacalcitol in patients with psoriasis vulgaris who have already been treated with another high-concentration vitamin D3 ointment, calcipotriol or maxacalcitol. The psoriasis area and severity index score was improved in more than half the patients after changing to the tacalcitol ointment. Many patients treated with maxacalcitol once a day achieved greater clinical improvement by changing to high-concentration tacalcitol. In contrast, some patients who had responded to a high-concentration tacalcitol ointment showed exacerbation after changing to maxacalcitol once a day. Interviews with 50 patients (including the 34 patients enrolled in the present study) indicated that high-concentration tacalcitol ointment was an acceptable therapy in terms of the number of daily applications and drug cost. The results of this clinical study suggest that high-concentration tacalcitol ointment meets the preference of many patients who wish to use an ointment once a day.

Topics: Calcitriol; Dihydroxycholecalciferols; Drug Administration Schedule; Humans; Ointments; Patient Acceptance of Health Care; Prescription Fees; Psoriasis; Severity of Illness Index; Treatment Outcome

In this study, we aimed to compare the clinical effectiveness of highly-concentrated tacalcitol ointment daily versus intermittent application in patients with psoriasis vulgaris who simultaneously took a low dose of cyclosporin. All the patients in both groups showed significant improvements, and the patients in the intermittent application group obtained more patient satisfaction in cost performance. The treatment cost of low-dose cyclosporin and intermittent application of highly-concentrated tacalcitol ointment was less than half of that of high-dose cyclosporin and daily application of highly-concentrated tacalcitol ointment. This preliminary study suggests that the combination therapy with low-dose cyclosporin administration and intermittent application of highly-concentrated tacalcitol is effective, safe and provides acceptable costs for the treatment.

Topics: Administration, Topical; Adult; Aged; Cyclosporine; Dihydroxycholecalciferols; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Ointments; Patient Satisfaction; Probability; Prospective Studies; Psoriasis; Risk Factors; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome

A group of vitamin D derivatives has revealed to be an efficient treatment for psoriasis. Different types of studies have been designed to confirm the efficacy of its use without relevant side-effects.. Evaluation of tolerability and efficacy of tacalcitol ointment in moderate psoriasis.. A 2-month multicentre prospective open-label observational study in patients with psoriasis treated with tacalcitol ointment.. A cohort of patients with psoriasis vulgaris seeking medical advice and being treated with tacalcitol based on the decision of their dermatologists was selected. A 2-month follow-up was performed to assess efficacy and tolerability of tacalcitol in an ointment formulation (4 microg/g) once daily. A psoriatic lesion was selected in each patient in order to assess clinical symptoms (erythema, desquamation and thickness) by means of five-point scale: 0 (none) to 4 (maximal severity). Percentages of involved skin, adverse effects, physicians' global assessments of efficacy and tolerability, and patients' global satisfaction scores were also evaluated after 15-30 days (first visit) and 2 months (second visit) of treatment.. A total of 556 patients were included. Mean psoriasis duration was 10.1 years (range, 0-61 years). Follow-up data were available for 493 patients in first follow-up visit and 449 in second (final) visit. Adverse events were uncommon (1.0% and 0.6% of patients in first and second follow-up visits, respectively). At first follow-up visit, mean decrease in selected lesions surface area (from a baseline value of 185.8 cm(2) per lesion) was 11.1 cm(2) (95% CI, 1.6-20.6; P = 0.0213). After 2 months of treatment, mean scores for erythema, desquamation and thickness changed from 2.2 +/- 0.8 to 1.1 +/- 0.8 (19% of patients with no erythema at final visit); from 2.4 +/- 0.8 to 0.6 +/- 0.7 (55% of patients with no desquamation); and from 2.2 +/- 0.9 to 0.8 +/- 0.6 (51% of patients with less thickness), respectively. Mean percentage of total body skin involvement was 14% (7.5% and 6.9% of anterior and posterior body surface, respectively). After 2 months of treatment, a 3.2% (95% CI, 2.7-3.8; P = 0.0001) and 3.0% (95% CI, 2.4-3.6; P = 0.0001) decrease was observed in the percentage of involved anterior and posterior skin surface area, respectively. Efficacy and tolerability evaluation by investigators was very good or good in 94% and 74% of patients, respectively; 78% of patients evaluated study treatment as satisfactory/very satisfactory. More than 80%, 50-80% and less than 50% of prescribed doses were used by 88%, 9.3% and 2.3% of patients, respectively.. Tacalcitol was highly effective in the symptomatic treatment of moderate psoriasis. Compliance was very high, probably due to the easy and convenient application. Physicians' global assessments of tacalcitol were excellent, both for tolerability and efficacy. Excellent tolerability was confirmed by the low rate of adverse events. Our results in an everyday clinical setting show that tacalcitol is a useful therapy in patients with moderate psoriasis.

Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Aged, 80 and over; Child; Dermatologic Agents; Dihydroxycholecalciferols; Female; Humans; Male; Middle Aged; Ointments; Prospective Studies; Psoriasis; Severity of Illness Index; Spain; Treatment Outcome

Daivobet is a once-daily treatment of psoriasis vulgaris containing betamethasone dipropionate and calcipotriol in a new ointment vehicle.. To assess the cost-effectiveness of once-daily treatment with Daivobet (4 weeks) followed by calcipotriol (4 weeks) compared to tacalcitol (8 weeks).. Resource utilization was assessed within a double-blind 8-week clinical trial (all treatments for psoriasis, adverse events and concomitant dermatological medication), estimated from the French societal perspective.. Total direct medical costs for psoriasis were comparable (Daivobet: EUR 107.53 and tacalcitol EUR 113.50) despite a higher acquisition cost for Daivobet. The probability of > or =75% reduction in the Psoriasis Area and Severity Index (effectiveness criterion) was 46.6% with Daivobet and 13.9% with tacalcitol at 4 weeks, and 44.6 and 23.8%, respectively, at 8 weeks (both: p < 0.001). Over 8 weeks, Daivobet was almost twice as cost-effective as tacalcitol (EUR 241.22 per successful treatment vs. EUR 476.70); this result was robust to sensitivity assumptions.. Daivobet is more effective and less costly than tacalcitol for treating psoriasis.

Topics: Administration, Topical; Adult; Aged; Betamethasone; Calcitriol; Confidence Intervals; Cost-Benefit Analysis; Dihydroxycholecalciferols; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Costs; Europe; Female; Follow-Up Studies; Humans; Male; Middle Aged; Ointments; Probability; Psoriasis; Reference Values; Risk Factors; Severity of Illness Index; Treatment Outcome

The scalp is a problematic area in psoriasis where treatment is often difficult. The lesions often extend beyond the hairline to involve the forehead, neck and sensitive facial skin. Topical corticosteroids and potentially irritant topical preparations have only limited utility in these sensitive areas. Most of the patients additionally suffer from psychosocial problems due to the visibility of lesions.. The aim of this multicenter, prospective, randomized, double-blind study, was to assess efficacy, safety and tolerability of once daily tacalcitol emulsion (4 micro g/g) compared to placebo in the treatment of scalp psoriasis.. To determine efficacy, safety and tolerability, 273 patients with mild to moderate scalp psoriasis were treated over a 8-week period. Response to treatment was evaluated using the sum score of erythema, infiltration and scaling. Global improvement of psoriasis was rated by the investigators and the patients using a 5-point scale. In addition the single scores of erythema, infiltration and scaling were assessed by the investigators, and the patients were asked to evaluate the intensity of itching and scaling over the treatment period.. Tacalcitol was significantly superior to placebo in reducing the severity of scalp psoriasis. At the end of the study, the median sum score decreased by 53% in the tacalcitol group and was significantly better than placebo with 30% (p<0.0001). Global assessment of improvement was significantly greater in the tacalcitol group in both investigator and patient evaluation. 80% of patients on tacalcitol showed improvement to clearance and was statistically significant better than placebo (p <0.0001) in the investigator rating after 8 weeks. Tacalcitol was significantly superior to placebo in reducing erythema, scaling and infiltration, and in the patient assessment in reducing scalp scaling and itching. Treatment was very well tolerated. Local reactions were transient and uncommon. Their incidence was similar in both treatment groups. No serious side effects were reported, including those relating to calcium homeostasis or vitamin D(3) metabolism. No changes in mean levels of serum calcium, parathyroid hormone (PTH), calcitriol and in 24h-urinary excretion were observed.. The results of this study indicate that topical application of tacalcitol (4 micro g/g) emulsion once daily is an effective, safe and very well- tolerated treatment for scalp psoriasis.

Topics: Adolescent; Adult; Aged; Calcium; Data Interpretation, Statistical; Dermatologic Agents; Dihydroxycholecalciferols; Double-Blind Method; Emulsions; Female; Follow-Up Studies; Homeostasis; Humans; Male; Middle Aged; Placebos; Prospective Studies; Psoriasis; Safety; Scalp Dermatoses; Time Factors

A two-compound product containing calcipotriol 50 microg/g and betamethasone dipropionate 0.5 mg/g (Daivobet, Dovobet) has been demonstrated to be an effective, once daily, treatment for psoriasis vulgaris.. To compare the efficacy and safety of treatment with the two-compound product for 4 weeks followed by calcipotriol for 4 weeks, with that of tacalcitol for 8 weeks in patients with stable psoriasis vulgaris.. 501 patients were randomised to double-blind treatment with the two-compound product followed by calcipotriol 50 microg/g once daily, or to tacalcitol 4 microg/g once daily.. Treatment with the two-compound product/calcipotriol was significantly more effective than tacalcitol in terms of mean percentage PASI reduction (65.0 vs. 33.3% at week 4 and 59.0 vs. 38.4% at week 8; p < 0.001 for both).. A treatment regimen comprising calcipotriol/betamethasone ointment (Daivobet) for 4 weeks followed by calcipotriol for 4 weeks is superior to tacalcitol ointment for 8 weeks in patients with psoriasis vulgaris.

Topics: Administration, Topical; Adolescent; Adult; Betamethasone; Calcitriol; Confidence Intervals; Dihydroxycholecalciferols; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Odds Ratio; Prospective Studies; Psoriasis; Reference Values; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome

Psoriasis is an immunogenetic disorder. Factor XIIIa+ dermal dendrocytes (DD) are part of the pathobiological changes in the plaque type of the disease.. The present study aimed at comparing the effect of 3 vitamin D(3) derivatives on the epidermis, microvasculature and DD in psoriasis.. Twenty men suffering from chronic plaques of psoriasis on the trunk were enrolled in this study. They applied twice a day for 3 weeks calcipotriol, tacalcitol and calcitriol, each to one plaque. Another similar lesion received petrolatum as a placebo treatment. Skin biopsies were taken at entry and at completion of the 3-week treatment phase. Immunohistochemistry was performed using the lectin of Ulex europaeus and an antibody to factor XIIIa. Computerized image analysis served to measure the stratum Malpighii area, the microvasculature area and the DD numerical density in the papillary dermis.. At entry in the study, the 4 test sites were indistinguishable with regard to the stratum Malpighii area, the papillary microvasculature area and the papillary DD density. The 3 histometric parameters appeared correlated with each other. At completion of the 3-week treatment phase, the 3 vitamin D derivatives had decreased the size of the stratum Malpighii. In addition, calcitriol had also reduced the DD density in the papillary dermis. No other significant changes were yielded.. As assessed by histometry, the psoriatic epidermis responded to a short treatment using the 3 vitamin D derivatives. The better result compared to the control site was achieved by calcitriol. DD appeared to be most controlled by the same drug. The microvasculature did not appear to be decreased at the 3-week time point in treatment.

Topics: Adult; Calcitriol; Calcium Channel Agonists; Dermatologic Agents; Dihydroxycholecalciferols; Humans; Male; Psoriasis; Statistics, Nonparametric

Numerous studies have shown that the additional administration of topical or systemic antipsoriatic agents might serve as an effective means to increase the efficacy of photochemotherapy [psoralen plus ultraviolet (UV) A (PUVA)] for psoriasis.. To compare the therapeutic response to tacalcitol plus PUVA, tazarotene plus PUVA and PUVA monotherapy in patients with chronic plaque-type psoriasis. In addition, we also assessed the duration of remission induced by each regimen and the tolerability of the two combination treatments.. Thirty-one patients with chronic plaque-type psoriasis were included in this observer-blinded, intrapatient comparison trial. PUVA treatment was given four times weekly. Additionally, tacalcitol ointment and 0.1% tazarotene gel were applied separately on two target areas once daily in the evening. At the onset of therapy and every 2 weeks thereafter the response to treatment was determined by the Psoriasis Severity Index score, which assesses the degree of erythema, infiltration and scaling of the psoriatic lesions. After complete or near complete clearing patients were followed-up until relapse.. Twenty-four patients completed the study. The treatment requirements to induce complete or near complete clearing were significantly lower for both combination treatments than for PUVA monotherapy (P < 0.01). The median cumulative UVA dose and number of exposures were 30.6 J cm-2 (95% confidence interval, CI 22.5-71.2) and 14 (95% CI 11-16) for tacalcitol plus PUVA, 32.3 J cm-2 (95% CI 22.5-73.8) and 14 (95% CI 11-19) for tazarotene plus PUVA, and 37.0 J cm-2 (95% CI 29.5-83.9) and 16 (95% CI 14-22) for PUVA monotherapy. No difference between the three regimens was observed with regard to duration of remission. Adverse reactions occurred more often with 0.1% tazarotene than with tacalcitol but were in general mild and completely reversible upon using a lower concentration of 0.05% tazarotene.. Tacalcitol ointment and tazarotene gel are both comparably effective in improving the therapeutic result of PUVA therapy in patients with chronic plaque-type psoriasis. Besides accelerating the treatment response, both agents, by virtue of their UVA dose-sparing effect, might also help to reduce possible long-term hazards of PUVA treatment.

Topics: Adult; Chronic Disease; Combined Modality Therapy; Dermatologic Agents; Dihydroxycholecalciferols; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nicotinic Acids; Psoriasis; PUVA Therapy; Radiation Dosage; Severity of Illness Index

As psoriasis patients often require continuous treatment optimal therapy has to provide efficacy and a good safety profile over the long term.. The aim of this multicentre study was to assess the efficacy, safety and tolerability of tacalcitol (4 microg g(-1)) ointment (Curatoderm, Hermal, Reinbek, Germany) applied once daily over a treatment period of 18 months.. Efficacy parameters were Psoriasis Area Severity Index (PASI), based on summed scores of erythema, infiltration and scaling and total body surface involvement (TBI). Safety assessment included serum levels of calcium, parathyroid hormone, calcitonin, 1,25-dihydroxy vitamin D3 (calcitriol); urinary calcium, creatinine, calcium/creatinine ratio in spot and 24-h urine and urinary alpha(1)-microglobulin. A group of 304 patients with chronic plaque psoriasis, covering between 7% and 20% of the body surface area was included for the initial treatment phase of 3 months. Of the 257 patients who completed the initial 3 months, 197 patients continued in a second treatment phase of 15 months.. Tacalcitol treatment proved to be effective in reducing the severity of psoriasis and maintained therapeutic response over the study period. The median PASI fell from 9.5 to 4 .6 at month 3 and to 3.25 at month 18 (P < 0.0001). The median improvement in TBI was 30% at month 3 and 50% at month 18. In no patient was there any relevant disturbance of calcium homeostasis. There were no significant changes in mean values of serum calcium, parathyroid hormone and calcitriol. Additionally no significant changes in 24-h urinary excretion evaluation were observed. There was no correlation between levels of serum calcium or urinary calcium and amount of tacalcitol ointment used, even in the patients requiring the largest amounts of ointment (up to 13 g day(-1) and up to 20% of body area affected). Treatment was generally well tolerated and there were no serious or unexpected adverse events reported. However, discontinuation of treatment as a result of skin irritation was seen in 5.9% of patients. The greatest frequency of cutaneous side-effects occurred during initial treatment and the incidence decreased markedly as the treatment was well-tolerated with continued use.. Tacalcitol ointment once daily was demonstrated to be efficacious, safe and well tolerated in the long-term control of plaque psoriasis in patients with up to 20% body surface involvement.

Topics: Adolescent; Adult; Aged; Calcitonin; Calcitriol; Calcium; Chronic Disease; Dermatologic Agents; Dihydroxycholecalciferols; Erythema; Female; Homeostasis; Humans; Male; Middle Aged; Ointments; Parathyroid Hormone; Prospective Studies; Psoriasis; Time Factors

Various studies have shown the benefit of topical vitamin D(3) analogues in the treatment of mild to moderate plaque psoriasis.. Assessment of the efficacy, tolerability and safety of tacalcitol ointment in the long-term treatment of chronic plaque psoriasis in daily dermatological practice.. In this open, multicentre, clinical phase IV study with a pre/post comparison design, 157 patients with chronic plaque psoriasis were included. Patients showing chronic plaque psoriasis, covering 7-20% of their body area, were treated with tacalcitol ointment (4 microg/g, Curatoderm) once daily and were assessed at baseline and monthly during the 6-month treatment period. The efficacy parameter psoriasis area and severity index (PASI) and total body surface involvement were assessed at each visit. Laboratory parameters were assessed at the beginning and at the end of the study. Adverse events were recorded at each visit.. The mean PASI score decreased by 67%, and a marked reduction in sum scores of erythema, infiltration and desquamation was detected. The body area affected declined by 33% from 13.3 to 8.8%. There were no changes in laboratory parameters, and no case of hypercalcaemia was observed. No serious adverse events occurred during the study period. The recorded local side-effects were usually transient and mainly mild.. Tacalcitol ointment is safe, well tolerated and provides a further option for patients with psoriasis up to 20% body surface affected. Tacalcitol treatment can be recommended as effective therapy for long-term control of chronic plaque psoriasis in dermatological practice.

Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Chronic Disease; Dermatologic Agents; Dihydroxycholecalciferols; Female; Humans; Male; Middle Aged; Ointments; Psoriasis; Treatment Outcome

Topics: Adult; Combined Modality Therapy; Dermatologic Agents; Dihydroxycholecalciferols; Female; Humans; Male; Middle Aged; Psoriasis; Ultraviolet Therapy

In the treatment of psoriasis with topical vitamin D3 analogues, lesional and perilesional irritation is the main side-effect. The aim of this study was to investigate whether local side-effects generated by tacalcitol, a vitamin D3 analogue, show concentration dependence. 3 different concentrations of tacalcitol (0.4; 4; 40 microg/g ointment) and the vehicle were applied on normal skin of the back of 25 healthy volunteers under occlusive conditions for 5 days. Assessment of erythema, infiltration and scaling as well as measurement of transepidermal water loss (TEWL) was performed on days 1 to 5. On day 5, additional skin barrier tests (DMSO test, alkali resistance test) were performed. Erythema and slight infiltration, but no scaling, were observed in a number of subjects without significant differences. TEWL also did not show significant differences for the test formulations, though there was a tendency towards lower values in the untreated areas. In the skin barrier tests, a tendency towards higher alkali resistance in the test areas treated with 40 microg tacalcitol/g ointment was detected. Thus, under occlusive conditions, the irritant potential of tacalcitol is very low. There is no convincing evidence of concentration dependence in irritation generated by tacalcitol when applied under occlusive conditions.

Topics: Administration, Topical; Adult; Dermatologic Agents; Dihydroxycholecalciferols; Dose-Response Relationship, Drug; Double-Blind Method; Erythema; Evaluation Studies as Topic; Female; Humans; Irritants; Male; Middle Aged; Ointments; Psoriasis; Severity of Illness Index

During the last decade, novel analogues of 1alpha,25-dihydroxy vitamin D3 have been developed for the treatment of psoriasis. Recently, the efficacy of short-term treatment with the novel derivative tacalcitol (1alpha,24-dihydroxy vitamin D3) has been documented. However, data on the long-term effect of tacalcitol on psoriatic skin are sparse. In this study, we assessed the cell characteristics of the psoriatic epidermis after treatment with tacalcitol for up to 24 weeks. We investigated how long-term treatment with tacalcitol modulates the percentages of differentiated keratinocytes, inflammation cells and basal keratinocytes, and the percentage of cells in the SG2M phase in the basal cell population. From 11 patients who were treated with tacalcitol for up to 18 months, we obtained single-cell suspensions of a representative psoriatic lesion after 0, 8, 12, 18 and 24 weeks of treatment. A Psoriasis Area and Severity Index was performed at each visit as well. Cell suspensions were stained with markers for inflammation (Vim3B4), differentiation (RKSE60) and proliferation (TO-PRO-3 iodide) and analysed flow cytometrically. Clinically, patients improved significantly after 8 weeks of treatment. This clinical effect was preserved for the rest of the period of treatment with no further significant improvement. Proliferative activity also decreased significantly after 8 weeks of treatment. Proliferation did not show further significant decreases or habituation after 12, 18 and 24 weeks. For inflammation, no statistically reliable trends could be seen. Differentiation improved significantly after 8 weeks of treatment, but decreased again significantly after 12 weeks. In the period from 12 to 24 weeks, no further significant change was observed. We conclude that tacalcitol is an effective antipsoriatic drug. Prolonged treatment with tacalcitol will generally maintain improvement at the level reached after 8 weeks. Owing to the beneficial effect on both clinical state and proliferation, tacalcitol is likely to be an adequate maintenance therapy.

Topics: Anti-Inflammatory Agents; Cell Differentiation; Cell Division; Dihydroxycholecalciferols; Drug Administration Schedule; Epidermis; Female; Flow Cytometry; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Psoriasis; Treatment Outcome

Once daily topical treatment of psoriasis with tacalcitol ointment (4 micrograms/g) was compared with twice daily treatment with calcipotriol ointment (50 micrograms/g) in a double-blind, randomized study over a treatment period of 8 weeks. The severity of pruritus, erythema, infiltration and scaling was scored on a scale from 0 to 4. These features were scored at the initiation of treatment, after 2, 4, 6 and 8 weeks of treatment, and at 4 weeks after discontinuation of treatment. The sum score was the total score for erythema, infiltration and scaling. Serum levels of calcium, phosphate, ionized calcium and intact parathyroid hormone were used as safety parameters. Two hundred and eighty-seven adults with stable plaque psoriasis participated and were treated at least once. Both tacalcitol and calcipotriol ointments effectively reduced the severity of psoriasis. The mean reduction in the sum score in the intention-to-treat population of 287 patients was 4.03 in the group treated with tacalcitol compared with 5.05 in the group treated with calcipotriol. The mean baseline sum scores were 7.64 and 7.15, respectively. The acceptability of both ointments was excellent, and none of the patients had adverse effects in terms of increased serum calcium or other alterations in calcium metabolism. Although less effective than calcipotriol ointment used twice daily, tacalcitol ointment is an effective and useful once daily treatment of chronic plaque psoriasis.

Topics: Adolescent; Adult; Aged; Calcitriol; Calcium; Dermatologic Agents; Dihydroxycholecalciferols; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Patient Satisfaction; Psoriasis; Severity of Illness Index; Treatment Outcome

Tacalcitol is a vitamin D analogue which ahs been developed for the therapy of psoriasis vulgaris. The treatment with a twice daily application of 2 micrograms/g ointment is efficacious and safe in Japanese patients. The objective of this randomized, placebo-controlled, intraindividual right-left comparison was to investigate the efficacy and safety of 8 weeks' therapy with a once daily application of a 4 micrograms/g tacalcitol ointment in Caucasian psoriatics. The data on 122 male and female patients were analysed. The score sum of erythema, infiltration and desquamation was influenced significantly more by tacalcitol ointment than by placebo (P < 0.0001) at every control point, starting from week 2. With regard to the individual symptoms of desquamation, infiltration and erythema, the treatment with tacalcitol was also superior to placebo treatment beginning at week 2. Qualitatively, the same results were obtained with the preference assessment of both treated body sides and also the global assessments of efficacy and benefit. Symptoms of local skin irritation which may be related to the active compound or the ointment base were reported by 12.3% of patients. In only one patient, irritation required discontinuation of tacalcitol treatment. Laboratory criteria, including serum calcium, serum phosphate and serum levels of calcitonin, parathormone, 1 alpha, 24-dihydroxyvitamin D3 and 25-hydroxyvitamin D3, did not reveal any changes of clinical relevance during or after treatment. Furthermore, the global assessment of tolerance was good or very good in more than 90% of cases. The results of this study demonstrate that the once daily application of a 4 micrograms/g tacalcitol ointment is an efficacious therapy for psoriasis vulgaris in Caucasian patients, and that its tolerance is good, wherever the lesion is located, including on the face.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Dermatologic Agents; Dihydroxycholecalciferols; Double-Blind Method; Female; Humans; Male; Middle Aged; Ointments; Psoriasis; Time Factors; Treatment Outcome

Topics: Calcitriol; Dermatologic Agents; Dihydroxycholecalciferols; Epidermis; Humans; Psoriasis; Transglutaminases

The clinical efficacy and tolerability of the vitamin D3 analogues calcitriol, calcipotriol and 1 alpha, 24 dihydroxyvitamin D3 in the treatment of psoriasis have been assessed in various clinical studies. In vitro and in vivo investigations have shown interference of these compounds with epidermal growth, keratinisation and inflammation. In this study we quantified the in vivo cell biological effects during treatment of psoriatic plaques with 1 alpha, 24 dihydroxyvitamin D3. By using a flow cytometric triple labelling procedure, we could discriminate different epidermal subpopulations, permitting precise assessment of epidermal cell cycle kinetics. Twenty patients with plaque-type psoriasis were treated in a double-blind placebo-controlled left-right comparative study with 1 alpha, 24 dihydroxyvitamin D3 ointment (4 micrograms/g applied once daily) for 8 weeks. Epidermal cell suspensions prepared from keratotome biopsies taken before and after treatment were stained with TO-PRO-3 iodide (a new DNA fluorochrome) and monoclonal antibodies against keratin 10 (as a marker for differentiation) and vimentin (as a marker for inflammation), simultaneously. The flow cytometric analyses showed a significant decrease of proliferating basal keratinocytes in verum-treated lesions, whereas such a decrease was not observed in placebo-treated lesions. The amount of keratin 10-positive keratinocytes increased and the presence of vimentin-positive cells decreased in cell suspensions derived from both verum- and placebo-treated lesions, but these effects were not significant. We conclude that multiparameter flow cytometry promises to be an adequate approach to assess the interference of antipsoriatic treatments with cutaneous inflammation, epidermal proliferation and keratinisation. Topical 1 alpha, 24 dihydroxyvitamin D3 seems to exert its in vivo antipsoriatic effect mainly through an inhibition of epidermal growth.

Topics: Administration, Cutaneous; Adult; Aged; Biopsy; Cell Cycle; Cell Differentiation; Cell Division; Cells, Cultured; Dermatologic Agents; Dihydroxycholecalciferols; DNA; Double-Blind Method; Epidermis; Female; Flow Cytometry; Fluorescent Dyes; Humans; Inflammation; Keratins; Male; Middle Aged; Placebos; Psoriasis; Vimentin

The aim of the present study was to discover to what extent 1,24(OH)2D3 ointment (tacalcitol; 4 micrograms/g) can modulate epidermal proliferation and keratinization, and several aspects of inflammation. Ten patients with psoriasis vulgaris were included in a placebo-controlled, double-blind study, using 1,24(OH)2D3 ointment (4 micrograms/g). Before, and after 8 weeks of treatment, punch biopsies were taken from lesions treated with the active agent and placebo-treated lesions. An immunohistochemical study was carried out using monoclonal antibodies against the hyperproliferation-associated keratin 16, against cycling nuclei, filaggrin, involucrin, T lymphocytes, Langerhans cells, CD14 and polymorphonuclear leucocytes (PMN). The Wilcoxon test for matched pairs was used for statistical analysis of results. The biopsies from the lesions treated with the active agent showed a statistically significant change towards normalization of all aspects of inflammation studied, and of epidermal proliferation and keratinization, but there did not appear to be any effect on Langerhans cells. The only parameter which showed a significant alteration in the placebo-treated lesions was the number of cycling nuclei in the epidermis (P < or = 0.02). However, the biopsies from the plaques treated with the active agent showed a greater decrease of cycling cells (decrease: Mactive = 70, Mplacebo = 53) and a lower P-value (< or = 0.01). We therefore conclude that at the cell biological level 1,24(OH)2D3 ointment (4 micrograms/g) has a substantial effect on several cell types, with regard to inflammation, epidermal proliferation and keratinization, with the exception of Langerhans cells.

Topics: Cell Division; Dihydroxycholecalciferols; Double-Blind Method; Epidermis; Filaggrin Proteins; Humans; Immunohistochemistry; Inflammation; Keratins; Psoriasis

Transdermal absorption of tacalcitol from the ointment containing 2 micrograms/g was studied using hairless rat and human skin. In the animal experiments, a non-negligible amount of tacalcitol was absorbed transdermally, whereas in the case of human skin, this compound was hardly absorbed at all. A placebo-controlled double-blind right/left comparison confirmed that this ointment is effective and safe for the treatment of psoriasis.

Topics: Animals; Dihydroxycholecalciferols; Double-Blind Method; Humans; Ointments; Psoriasis; Rats; Rats, Wistar

Topics: Administration, Cutaneous; Anti-Bacterial Agents; Antibiotic Prophylaxis; Calcium; Child, Preschool; Dermatologic Agents; Dihydroxycholecalciferols; Humans; Male; Pancreas; Pancreatitis; Psoriasis; Tomography, X-Ray Computed

Vitamin D analogues and NBUVB phototherapy are both well-established modalities of treatment in psoriasis. The objective of this open label, intraindividual, left right study was to compare two different vitamin D analogues, calcipotriol and tacalcitol, in combination with NBUVB phototherapy in chronic stable plaque psoriasis.. Thirty patients with stable plaque psoriasis were enrolled for a 12-week clinical trial. The target lesion on left side was treated topically with tacalcitol ointment once daily, while that on the right side was treated with calcipotriol ointment twice daily. NBUVB phototherapy was given thrice weekly. Efficacy was assessed by target plaque scoring.. Both therapies resulted in statistically significant reduction in erythema, scaling, thickness and target plaque score, seen as early as 2 weeks into therapy. However, calcipotriol combination led to an earlier clearance of plaques and a lesser relapse rate than tacalcitol combination. The number of treatment sessions and cumulative NBUVB doses were significantly lower in the calcipotriol-treated group.. Both vitamin D analogues appear to be safe, effective and cosmetically acceptable, calcipotriol being more efficacious, well tolerated with a rapid onset of action and a better maintenance of response.

Topics: Adult; Calcitriol; Combined Modality Therapy; Dermatologic Agents; Dihydroxycholecalciferols; Female; Humans; Male; Ointments; Prospective Studies; Psoriasis; Severity of Illness Index; Ultraviolet Therapy; Young Adult

Topics: Administration, Cutaneous; Anti-Inflammatory Agents; Attitude of Health Personnel; Betamethasone; Calcitriol; Clobetasol; Dihydroxycholecalciferols; Dose-Response Relationship, Drug; Drug Prescriptions; Gels; Humans; Immunosuppressive Agents; Medication Adherence; Practice Patterns, Physicians'; Psoriasis

Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor which mediates a variety of functions in the skin including cutaneous inflammation. SLIGKV-NH(2) , an agonist peptide for PAR2, enhanced the interleukin (IL)-17-induced production of two CXC chemokines, CXCL1 (GRO-α) and CXCL8 (IL-8), in normal human epidermal keratinocytes (NHEK) in a concentration-dependent manner. The enhanced production of those chemokines was suppressed by a PAR2-specific siRNA. The SLIGKV-NH(2) -induced production of both CXCL1 and CXCL8 was markedly reduced by cyclosporine A. The enhanced production of CXCL1 was suppressed by 1α, 24R-dihydroxyvitamin D(3) , an active form of vitamin D(3) , and weakly by glucocorticoids, dexamethasone and clobetasol propionate, whereas production of CXCL8 was not altered by any of those receptor agonists. In psoriatic skin, the thickened upper spinous layer of the epidermis was positive for PAR2 protein and the expression of the IL17A mRNA was increased. These results suggest that the IL-17-induced pro-inflammatory reaction is enhanced by the activation of PAR2 in keratinocytes, and that the effect of PAR2 is differentially modulated by cyclosporine A, the active form of vitamin D(3) and glucocorticoids.

Topics: Cells, Cultured; Chemokine CXCL1; Clobetasol; Cyclosporine; Dexamethasone; Dihydroxycholecalciferols; Glucocorticoids; Humans; Inflammation Mediators; Interleukin-17; Interleukin-8; Keratinocytes; Oligopeptides; Psoriasis; Receptor, PAR-2; RNA, Messenger; RNA, Small Interfering

Psoriasis is a chronic inflammatory skin disease of unknown aetiology, and an active form of vitamin D(3) (1α,25-dihydroxyvitamin D(3)) and its analogues (VD3As) are widely used topical reagents for psoriasis treatment. Besides their well-known calcium homeostasis functions, VD3As have been shown to have various immune-modulating effects including the induction of thymic stromal lymphopoietin (TSLP), a master cytokine for inducing Th2 inflammation, in mouse models, but not yet in human psoriasis. VD3As also have been shown to induce cathelicidin, an antimicrobial peptide and strong inducer of innate immunity. Cathelicidin is overexpressed in psoriatic skin lesions; however, its role in this disease seems as yet inconclusive.. To clarify whether topical VD3As induce TSLP and cathelicidin, and to examine the modulation of expression patterns of related cytokines in human psoriatic lesions.. Skin biopsy samples from psoriatic lesions with or without VD3A treatment were subjected to immunohistochemical staining and quantitative reverse transcription-polymerase chain reaction analyses to measure the expression levels of various cytokines.. Significantly higher levels of TSLP, thymus and activation-related chemokine and CCR4 expression were observed in VD3A+ skin samples than in VD3A- samples. In contrast, significantly lower levels of interleukin (IL)-12/23 p40, IL-1α, IL-1β and tumour necrosis factor (TNF)-α expression were observed in the VD3A+ samples than in the VD3A- samples. Expression of cathelicidin was elevated in VD3A+ samples.. Topical VD3As induce TSLP and cathelicidin in psoriatic lesions, resulting in suppression of IL-12/23 p40, IL-1α, IL-1β and TNF-α, thereby ameliorating psoriatic plaques.

Topics: Administration, Cutaneous; Adult; Aged; Antimicrobial Cationic Peptides; Blotting, Western; Calcitriol; Cathelicidins; Cholecalciferol; Cytokines; Dermatologic Agents; Dihydroxycholecalciferols; Drug Therapy, Combination; Female; Humans; Interleukins; Male; Middle Aged; Psoriasis; Thymic Stromal Lymphopoietin; Tumor Necrosis Factor-alpha

Prolactin (PRL), a neuropeptide secreted by the anterior pituitary gland, possesses a variety of physiological actions. It has been implicated as an important immunomodulator and exerts a proliferative effect in cultured human keratinocytes via specific receptors. Some studies have indicated an increase in serum PRL levels in psoriasis and exacerbation of psoriasis when a prolactinoma is present.. To evaluate the correlation between serum PRL levels and Psoriasis Area and Severity Index (PASI).. Serum PRL levels were measured in 20 patients (10 mean, 10 women, age range 18-88 years) with plaque-type psoriasis before and after a 6-week period of topical treatment with tacalcitol ointment. Results were compared with a group of 20 healthy volunteers.. Serum PRL levels were significantly increased in the psoriatic group compared with the control group (P < 0.001) and were significantly reduced after treatment (P = 0.001). There was a correlation between pretreatment serum PRL levels and PASI (r = 0.33; P = 0.02).. These results indicate that serum PRL levels may serve as a biological marker of psoriatic disease activity.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Dermatologic Agents; Dihydroxycholecalciferols; Female; Humans; Male; Middle Aged; Ointments; Prolactin; Psoriasis; Regression Analysis; Severity of Illness Index; Treatment Outcome; Young Adult

The synthesis of the clinically important drug calcipotriol (2, MC903) is described as an example of a new and efficient approach to C24-hydroxylated analogs and metabolites of vitamin D3 (1). The key step of the process is the generation of the C24 stereocenter by DAIB [(-)-3-exo-(dimethylamino)isoborneol]-catalyzed addition of the alkenylzinc derivative of alkyne 3 to cyclopropylcarboxaldehyde.

Topics: Alcohols; Calcitriol; Catalysis; Cell Differentiation; Chemistry, Pharmaceutical; Dihydroxycholecalciferols; Drug Design; Humans; Models, Chemical; Molecular Conformation; Psoriasis; Stereoisomerism

Topics: Coal Tar; Dihydroxycholecalciferols; Drug Therapy, Combination; Humans; Occlusive Dressings; Photochemotherapy; Psoriasis; PUVA Therapy; Severity of Illness Index

Psoriasis is a very common dermatological disease affecting a large part of the world population. In its most common form, psoriasis vulgaris, many topical drugs are available to treat the localized forms, and the recurrence of the dermatosis. Among topicals, tacalcitol has been proven to be effective and devoid of side effects which are typical of Vitamin-D3 analogues or derivates. The aim of this retrospective study was to evaluate the efficacy of topical tacalcitol vs. calcipotriol and emollient treatment of the first recurring lesion in order to induce a longer remission period before the retreatment with nb-UVB phototherapy in a population of 90 psoriatic patients. In this trial, the time between the first relapsing plaque appearance and retreatment with nb-UVB resulted in 25, 16 and 11 days for tacalcitol, calcipotriol and emollient respectively, with a statistically significant difference for tacalcitol (p < 0.0001). These results proved that tacalcitol treatment is effective in increasing the time interval in consecutive phototherapy cycles and in reducing the total amount of UV exposure.

Topics: Administration, Topical; Adult; Calcitriol; Cohort Studies; Dermatologic Agents; Dihydroxycholecalciferols; Female; Humans; Male; Middle Aged; Psoriasis; Retrospective Studies; Treatment Outcome; Ultraviolet Therapy

Nail involvement is a common and distressing feature in the course of psoriasis. Although much progress has been made in the treatment of the disease, the presence of psoriasis in the nail continues to pose a challenge. In recent years, vitamin D3 analogs and a new formulation containing 8% clobetasol-17-propionate in a colourless nail lacquer vehicle have produced good results for the control of nail psoriasis.. To determine the efficacy and safety of the combined treatment of 8% clobetasol-17-propionate in a lacquer vehicle and tacalcitol ointment in nail psoriasis.. Fifteen patients with both nail bed and nail matrix psoriasis were included in the study. They were treated with a colourless nail lacquer containing 8% clobetasol-17-propionate applied at bedtime at the weekend, and with tacalcitol ointment under occlusion on the remaining days, for 6 months.. All 15 patients responded well to treatment. The therapeutic effect was very fast and directly related to the length of therapy. All nail alterations, including nail pain, were reduced, and the modified target Nail Psoriasis Severity Index fell by an average of 78% compared to baseline levels (+/-59.6, P < 0.0001).. Combined treatment with tacalcitol ointment and 8% clobetasol-17-propionate in a nail lacquer is a safe, effective treatment for nail bed and nail matrix psoriasis.

Topics: Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Clobetasol; Dihydroxycholecalciferols; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nail Diseases; Ointments; Psoriasis; Treatment Outcome

Topics: Adult; Dermatologic Agents; Dihydroxycholecalciferols; Humans; Hypercalcemia; Male; Pancreatitis, Acute Necrotizing; Psoriasis

A 6-year-old girl with a symmetric linear eruption on both of her legs, clinically and histologically resembling inflammatory linear verrucous epidermal nevus (ILVEN) or linear psoriasis (LP), with concomitant psoriasis of the guttata type and a positive family history of psoriasis is presented. The questions as to whether LP actually exists and ILVEN represents a distinct entity are still under debate.. The recent literature concerning case reports of ILVEN and LP is reviewed.. Case reports of ILVEN and LP can be subdivided into four different groups: (1) ILVEN with or without concomitant psoriasis, only in part reacting to antipsoriatic treatment, (2) ILVEN without concomitant psoriasis, (3) LP with concomitant psoriasis vulgaris, with both groups 2 and 3 reacting successfully to antipsoriatic treatment, and (4) LP without concomitant psoriasis vulgaris and with no family history of psoriasis (very rarely reported).. It is hypothesized that inflammatory linear verrucous eruption besides nevoid psoriasis/LP represents a further segmental type 1/type 2 mosaic of psoriasis which, if a (verrucous) epidermal nevus exists, shows a high affinity of occurrence in close context to such a nevus. Heritability is thought to be possible.

Topics: Administration, Topical; Child, Preschool; Dermatologic Agents; Diagnosis, Differential; Dihydroxycholecalciferols; Female; Follow-Up Studies; Humans; Nevus; Ointments; Psoriasis; Skin Neoplasms

Topics: Administration, Topical; Alleles; Clinical Trials as Topic; Dermatologic Agents; Dihydroxycholecalciferols; Gene Frequency; Genotype; Homozygote; Humans; Polymorphism, Genetic; Psoriasis; Receptors, Calcitriol; Treatment Outcome

Topics: Administration, Topical; Dermatologic Agents; Dihydroxycholecalciferols; Eosinophilia; Female; Humans; Middle Aged; Ointments; Psoriasis; Severity of Illness Index; Treatment Outcome

This study focused on the effects of tacalcitol (1,24 (R) (OH)2D3, TV-02) ointment (20 micro g/g) on cutaneous inflammation, epidermal proliferation, and differentiation and compared them with tacalcitol ointment (2 micro g/g) and other anti-psoriatic ointments using hairless mice. Tacalcitol ointment (0, 2 and 20 micro g/g) significantly inhibited 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cutaneous inflammation, histopathologically. The effect of tacalcitol ointment (20 micro g/g) on cutaneous inflammation was much stronger than that of tacalcitol ointment (0, 2 micro g/g), and as effective as calcipotriol ointment (50 micro g/g) or betamethasone valerate ointment (1.2 mg/g). Tacalcitol ointment (20 micro g/g) also significantly inhibited TPA-induced myeloperoxidase (MPO) activity, as effectively as calcipotriol ointment (50 micro g/g) or betamethasone valerate ointment (1.2 mg/g). The effect of tacalcitol ointment on epidermal proliferation [ornithine decarboxylase (ODC) activity] and differentiation [transglutaminase (TGase) activity] was dose-dependent from 0 micro g/g to 20 micro g/g. The effect of tacalcitol ointments on epidermal proliferation was significant at the doses of 2 micro g/g and 20 micro g/g, and that on epidermal differentiation was significant at the doses of 0.2 micro g/g or more. The effect of tacalcitol ointment (20 micro g/g) on epidermal differentiation was significantly stronger than tacalcitol ointment (2 micro g/g). In this study, tacalcitol ointment (20 micro g/g) was found to have a marked effect on cutaneous inflammation and improved effect on epidermal differentiation, although tacalcitol ointment (2 micro g/g) also had significant effects on epidermal proliferation and differentiation. These findings support the clinical effectiveness of tacalcitol ointment (20 micro g/g) against psoriasis.

Topics: Administration, Topical; Animals; Biopsy, Needle; Dermatitis; Dihydroxycholecalciferols; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Epidermis; Female; Immunohistochemistry; Mice; Mice, Hairless; Ointments; Psoriasis; Reference Values; Treatment Outcome

Tacalcitol is a synthetic vitamin D3 analogue developed for topical treatment of inflammatory skin diseases such as psoriasis. Hypercalcemia has not been previously reported during treatment with topical tacalcitol. We experienced a male patient with psoriasis and hypertension whose conditions were treated with tacalcitol ointment and thiazide, respectively, resulting in hypercalciuria and hypercalcemia. After initiation of topical vitamin D3 ointment (20 micro g/g of tacalcitol) 10 g/day for the skin lesions, both the serum level of calcium and urinary excretion of calcium increased gradually. On day 28 of the treatment, his serum calcium levels had reached 3.55 mmol/l, and his urinary calcium excretion had also increased from 0.008 g/day to 0.475 g/day. The tacalcitol treatment was terminated, seven days later, the serum calcium level had returned to the reference range without any specific treatment. The present case is the first report of hypercalcemia induced by vitamin D3 ointment and thiazide simultaneously.

Topics: Administration, Cutaneous; Aged; Benzothiadiazines; Calcium; Dermatologic Agents; Diagnosis, Differential; Dihydroxycholecalciferols; Diuretics; Humans; Hypercalcemia; Hypertension; Iatrogenic Disease; Male; Ointments; Psoriasis; Sodium Chloride Symporter Inhibitors

We examined polymorphisms of vitamin D receptor (VDR) gene in Japanese patients with psoriasis vulgaris (PsV). We also studied the association between VDR gene polymorphisms and the response to vitamin D (VD) topical treatment in psoriatic patients. FokI, BsmI, ApaI and TaqI genotypes were determined by restriction fragment patterns in patients (n = 115) and controls (n = 69). In addition, 54 psoriatic patients were divided into two groups in terms of their response to VD (tacalcitol) topical treatment: non-responsive (n = 30) and responsive (n = 24) patients. The frequencies of B allele and t allele were lower in patients than in controls (9 vs. 19%: p < 0.01, 7 vs. 14%: p < 0.05, respectively). In regard to response to VD treatment, F allele was lower in non-responsive patients than in controls (47 vs. 64%, p < 0.05). We show that polymorphisms of VDR gene are associated with Japanese patients with PsV. Allelic variance in the VDR gene or other genes in linkage disequilibrium with this gene might predispose to the development of PsV.

Topics: Adult; Aged; Asian People; Dermatologic Agents; Dihydroxycholecalciferols; Female; Genotype; Humans; Japan; Male; Middle Aged; Polymorphism, Genetic; Psoriasis; Receptors, Calcitriol; Treatment Outcome

Sphingomyelin hydrolysis seems to be a ubiquitous pathway generating ceramide, an important cell response modifier. Upon agonist-stimulation this pathway is linked to biological responses as inhibition of proliferation, promotion of differentiation and induction of apoptosis. One of the agonists described is 1alpha,25-dihydroxyvitamin D3. Recently, we could demonstrate the existence of sphingomyelin hydrolysis in human primary keratinocytes as well as in the human keratinocyte cell line HaCaT after treatment with 1alpha,25-dihydroxyvitamin D3. In the present study we tested four vitamin D analogues on HaCaT keratinocytes for their ability to inhibit cell proliferation and to induce sphingomyelin hydrolysis. These analogues, calcipotriol, EB 1213, GS 1500 and tacalcitol inhibit cell growth after 48 hrs. of incubation and trigger the hydrolysis of sphingomyelin. Moreover, all analogues tested induce apoptotic cell death in HaCaT keratinocytes after 24 hrs. of incubation. This study indicates that sphingomyelin hydrolysis, subsequently leading to the elevation of cellular ceramide levels, may represent an important signal transduction pathway for 1alpha,25-dihydroxyvitamin D3 and its analogues in human keratinocytes. Possible differences of the mechanism underlying vitamin D-induced sphingomyelin hydrolysis has to be studied in more detail and may contribute to the antipsoriatic action of these analogues.

Topics: Apoptosis; Calcitriol; Cell Division; Cell Line; Dihydroxycholecalciferols; Humans; Keratinocytes; Psoriasis; Sphingomyelins; Vitamin D

We studied the effect of tacalcitol (1 alpha, 24 dihydroxy vitamin D3) ointment on clinical and immunohistochemical efficacy in psoriatic patients during 2 months of treatment. The psoriasis area and severity index decreased significantly after only 1 month and the total body surface index decreased 55% after 2 months. To characterize the epidermal compartment keratin 14, keratin 16, epidermal growth factor receptor, apoptotic and Ki-67 positive cells were examined. After 1 week of treatment no significant changes were found in any of these parameters. After 2 months, keratin 16 reached the levels observed in normal skin and Ki-67 and keratin 14 expression also reduced significantly. Epidermal growth factor receptor staining and the number of apoptotic cells did not alter during treatment. We conclude that tacalcitol is effective in the treatment of plaque psoriasis. Because the main epidermal effect observed immunohistochemically is a reduction in proliferation, a combination therapy using either corticosteroids, vitamin A derivatives or dithranol seems rational.

Topics: Administration, Cutaneous; Adult; Apoptosis; Dermatologic Agents; Dihydroxycholecalciferols; ErbB Receptors; Female; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Keratins; Ki-67 Antigen; Male; Middle Aged; Ointments; Psoriasis; Severity of Illness Index; Treatment Outcome

The chemokine RANTES is a chemoattractant for eosinophils, T lymphocytes of memory phenotype and monocytes, suggesting that it plays an important part in chronic inflammatory and allergic diseases. In various types of cells, RANTES production is markedly induced by tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma in combination. Psoriasis vulgaris is a chronic cutaneous inflammatory disease. Cytokines and chemokines produced by T cells and epidermal keratinocytes, such as interleukin (IL) 8, are involved in the pathogenesis of psoriasis. T-cell clones obtained from psoriatic skin have been shown to produce the Th1 cytokine IFN-gamma. In addition, abnormal expression of proinflammatory cytokines including TNF-alpha has been observed in psoriatic lesions. These reports led us to hypothesis that psoriatic skin could provide epidermal keratinocytes with TNF-alpha and IFN-gamma, so that keratinocytes could produce RANTES. In this study, we addressed the question as to whether RANTES was involved in psoriasis vulgaris. Immunohistochemistry of skin biopsies showed RANTES was present in the intercellular spaces between epidermal keratinocytes, in the fully developed lesions from the middle to the edge of psoriatic plaques, but not in the perilesional uninvolved and healthy control skin. Further, we confirmed the production of RANTES, together with IL-8, by cultured normal human epidermal keratinocytes, using an enzyme-linked immunosorbent assay. Stimulation with TNF-alpha and IFN-gamma in combination synergistically increased the RANTES production in this system. These results clearly demonstrate the expression of RANTES in psoriatic lesions and suggest the involvement of this chemokine in the outcome of cutaneous inflammatory diseases. Tacalcitol (1 alpha,24(R)-dihydroxyvitamin D3), an active vitamin D3 analogue, inhibited RANTES and IL-8 production in cultured normal epidermal keratinocytes. This result indicates that active vitamin D3 is effective in the regulation of chemokine production by epidermal keratinocytes, which may partly account for its action as an antipsoriatic drug.

Topics: Cell Culture Techniques; Chemokine CCL5; Cytokines; Dihydroxycholecalciferols; Dose-Response Relationship, Drug; Humans; Interferon-gamma; Interleukin-8; Keratinocytes; Psoriasis; Recombinant Proteins; Skin; Time Factors; Tumor Necrosis Factor-alpha

Topics: Adult; Anti-Inflammatory Agents; Dihydroxycholecalciferols; Down-Regulation; Female; Humans; Male; Middle Aged; Psoriasis; Receptors, Cytokine; Receptors, Interleukin-1; Receptors, Tumor Necrosis Factor

Various controlled studies have demonstrated the efficacy and safety of tacalcitol ointment (4 micrograms/g) in the treatment of psoriasis. Further data are now available from a multicentre post-marketing surveillance study involving more than 5000 outpatients. Once-daily treatment with tacalcitol resulted in a marked decrease of mean sum score (erythema, infiltration, scaling) from 6.3 to 2.7 score points in an average period of 61 days. Efficacy was assessed by dermatologists as 'very good' or 'good' in 71% of the patients. Local tolerance was stated to be 'very good' or 'good' in 94% of the patients. Only 1% of the patients experienced skin irritation. No case of hypercalcaemia was observed. Compared with conventional therapies, 52% of the patients saved up to half an hour of treatment time daily because of the once-daily application. Good local tolerance and a convenient treatment regimen may also help compliance.

Topics: Adolescent; Adult; Child; Child, Preschool; Dermatologic Agents; Dihydroxycholecalciferols; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Ointments; Product Surveillance, Postmarketing; Psoriasis; Time Factors

Calcipotriol, 1,25(OH)2D3 and 1,24(OH)2D3 are potent drugs for the treatment of psoriasis. It has recently been published that these compounds induce epidermal hyperproliferation in hairless mouse skin.. The aim of our study was to examine the effect of vitamin D3 derivatives on epidermal growth, keratinization and permeability barrier function in vivo.. Calcipotriol, 1,25(OH)2D3 and 1,24(OH)2D3 in isopropanol or in an ointment formula were applied to normal hairless mouse skin. Transepidermal water loss (TEWL), a marker of cutaneous barrier function, and epidermal proliferation were determined at different time points 0-264 h after treatment. In addition, light and electron microscopy studies were performed.. A single treatment in solution led to a transient (2- to 3-fold) increase in TEWL after application of calcipotriol or 1,25(OH)2D3 and to a 3- to 6-fold increase in epidermal proliferation after application of each of the compounds. Repeated applications also resulted in an up to 3-fold increase in TEWL which persisted for 3 days after the end of the treatment. By light microscopy an increase in epidermal thickness was observed. There was no sign of inflammation. Electron microscopy studies showed the formation of a transitional cell zone as a sign of a premature keratinization.. These results demonstrate that in normal mouse skin vitamin D3 and its analogues disrupt the epidermal permeability barrier by induction of epidermal proliferation and premature keratinization but without morphological signs of inflammation.

Topics: 1-Propanol; Administration, Cutaneous; Animals; Calcitriol; Cell Division; Cholecalciferol; Dermatologic Agents; Dihydroxycholecalciferols; Epidermis; Keratins; Male; Mice; Mice, Hairless; Microscopy, Electron; Ointments; Permeability; Psoriasis; Skin; Time Factors; Water Loss, Insensible

Topics: Administration, Topical; Calcitriol; Cross Reactions; Dermatitis, Allergic Contact; Dermatologic Agents; Dihydroxycholecalciferols; Humans; Hypersensitivity, Delayed; Male; Middle Aged; Patch Tests; Psoriasis

Establishing guidelines and experimental models preclinical and clinical evaluations of new agents for treatment, and/or prevention of human diseases has become a task of crucial importance. Psoriasis is such one disease holding great interest for dermatology owing to its high rate of incidence and complexity of treatment. However the absence of psoriatic lesions in animals and the inability to induce them, calls for experimental techniques both in vitro and in vivo. The purpose of this study was to evaluate experimentally the effects of tacalcitol on cell proliferation and differentiation process. Thereafter a human pilot study on psoriatic patients has been developed.

Topics: Administration, Topical; Adult; Animals; Anti-Inflammatory Agents; Dihydroxycholecalciferols; Disease Models, Animal; Female; Humans; Male; Mice; Middle Aged; Parakeratosis; Pilot Projects; Psoriasis; Skin

The 1,24(R)(OH)2D3 (tacalcitol) ointment (2 micrograms/g) is available commercially as an antipsoriatic drug in Japan, but the cream preparation of tacalcitol is still under development.. This study was conducted to compare the ability of tacalcitol cream and ointment to inhibit epidermal proliferation and induce epidermal differentiation.. We measured the ornithine decarboxylase activity and type I transglutaminase activity as indices of proliferation and differentiation, respectively, in hairless mice.. These effects were statistically equal to those of the ointment preparation at the same dose, 2 micrograms/g, without inducing hypercalcemia.. These findings suggest that topical application of 1,24(OH)2D3 cream (2 micrograms/g) might have the same potency as the ointment formulation in the treatment of psoriasis.

Topics: Administration, Topical; Animals; Calcium; Cell Differentiation; Cell Division; Dermatologic Agents; Dihydroxycholecalciferols; Dose-Response Relationship, Drug; Epidermis; Female; Mice; Mice, Hairless; Ointments; Ornithine Decarboxylase; Psoriasis; Transglutaminases

In this study, we examined the cutaneous effects of tacalcitol [1,24(R)(OH)2D3] on epidermal proliferation, differentiation, and skin inflammation in vivo using hairless mice. Tacalcitol was shown to inhibit epidermal proliferation using TPA-induced ornithine decarboxylase activity and DNA synthesis as indices, and the induction of epidermal differentiation using type I transglutaminase activity as an index. Tacalcitol also displayed an antiinflammatory effect on TPA-induced inflammatory changes histopathologically. These results confirm the clinical efficacy of tacalcitol in psoriasis, and suggest that it may be efficacious in the treatment of other inflammatory skin diseases.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Calcium; Cell Differentiation; Cell Division; Dermatitis; Dihydroxycholecalciferols; DNA; Enzyme Induction; Enzyme Inhibitors; Epidermal Cells; Epidermis; Female; Mice; Mice, Hairless; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Psoriasis; Tetradecanoylphorbol Acetate; Transglutaminases

Topics: Aged; Dermatitis, Allergic Contact; Dermatologic Agents; Dihydroxycholecalciferols; Female; Humans; Lymphocyte Activation; Psoriasis

Video-microscopy is a video-imaging system which permits direct visualization of the skin surface and capillaries, by using a microscope attached to a camera, a video-recorder and a printer. This technique provides information on the morphology of capillaries in vivo and has been used both for research into normal skin microcirculation and as a clinical method to detect capillary changes in psoriasis and other skin diseases. The aim of this study was to evaluate the morphology of capillaries in psoriatic plaques before and after treatment with tacalcitol, a new topical vitamin D3 analogue. Clinical evaluation was made after 3 and 6 weeks of therapy. After 3 weeks a reduction in erythema and scaling was noted; and areas in which capillaries were less tortuous became evident. After 6 weeks, capillaries were less dilated and tortuous in the whole plaque and had lost the large and tortuous appearance of active psoriasis.

Topics: Adult; Capillaries; Dihydroxycholecalciferols; Female; Humans; Male; Microscopy; Middle Aged; Psoriasis; Skin; Video Recording

Using cultured normal human keratinocytes, we compared the activities of 1 alpha,24-dihydroxyvitamin D3 (1,25(OH)2D3), a biologically active form, in inducing cell differentiation. Treatment with 10(-6) M of 1,24R(OH)2D3 and 1,25(OH)2D3 increased the number of involucrin positive cells (differentiated from 6.4% to 24.1% and 25.1%, respectively. These results indicate that 1,24R(OH)2D3 has an ability comparable to that of 1,25(OH)2D3 to induce cell differentiation in human keratinocytes. The clinical effectiveness of 1,24R(OH)2D3 for the treatment of psoriasis may be, in part, related to its direct effect on hyperproliferative keratinocytes.

Topics: Calcitriol; Cell Division; Cells, Cultured; Dihydroxycholecalciferols; Epidermis; Humans; Keratinocytes; Psoriasis

The effect of 1,24R-dihydroxyvitamin D3 (1,24R(OH)2D3), a synthetic analogue of a biologically active form of vitamin D3 (1,25-dihydroxyvitamin D3, 1,25(OH)2D3), on the growth of human keratinocytes cultured in serum-free medium was investigated. The growth of cultured normal human keratinocytes was inhibited by 65% by 10(-8)M 1,24R(OH)2D3 and by 90% by 10(-7)M 1,24(OH)2D3. It inhibited cell growth almost completely at 10(-6)M. The DNA synthesis of keratinocytes was also inhibited with 1,24R(OH)2D3 by 27% at 10(-8)M, 59% at 10(-7)M, and 92% at 10(-6)M. The inhibition of cell growth and DNA synthesis were more remarkable by 1,24R(OH)2D3 than by 1,25(OH)2D3. 1,24R(OH)2D3 also inhibited the growth of keratinocytes derived from patients with psoriasis vulgaris; the growth inhibitory effect was again more remarkable with 1,24R(OH)2D3 than with 1,25(OH)2D3. The viability and protein synthesis of keratinocytes were not affected by 1,24R(OH)2D3, suggesting that the growth inhibitory effect is due to its biological activity, not to cytotoxicity. The binding of [3H]-labeled 1,25(OH)2D3 to its receptor in the cytosolic fraction of cultured keratinocytes was competitively substituted by unlabeled 1,24R(OH)2D3 as well as 1,25(OH)2D3, suggesting that 1,24R(OH)2D3 binds to the 1,25(OH)2D3 receptor. It was found that the affinity of 1,24R(OH)2D3 for the receptor was slightly higher than that of 1,25(OH)2D3. These results demonstrate that 1,24R(OH)2D3 functions as a potent growth inhibitor in vitro in human keratinocytes from both normal and psoriatic epidermis, and it possesses a higher affinity for the 1,25(OH)2D3 receptor in cultured human keratinocytes. The difference in affinity of 1,24R(OH)2D3 for the 1,25(OH)2D3 receptor correlates with its greater inhibition of keratinocyte growth than 1,25(OH)2D3. 1,24R(OH)2D3 may be useful in the treatment of psoriasis.

Topics: Binding, Competitive; Calcitriol; Cell Division; Cell Survival; Cells, Cultured; Dihydroxycholecalciferols; DNA; Humans; Keratinocytes; Protein Biosynthesis; Psoriasis; Receptors, Calcitriol; Receptors, Steroid

1 alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to be a hormonally active form of vitamin D3 in the regulation of intracellular and extracellular calcium levels and of differentiation of myeloid cells and epidermal keratinocytes. We found that 1 alpha,24(R)-dihydroxyvitamin D3 (1,24(OH)2D3), a novel synthetic derivative of vitamin D3, is also active in regulating the differentiation of epidermal keratinocytes. 1,24(OH)2D3 had the same affinity as 1,25(OH)2D3 for a receptor isolated from the epidermis of newborn mice. The incubation of mouse epidermal keratinocytes with 1,24(OH)2D3 induced their differentiation in a time- and dose-dependent manner, as determined by the formation of a cornified envelope and an increase in the activity of transglutaminase. 1,24(OH)2D3 inhibited DNA synthesis of epidermal keratinocytes and also increased their cytosolic calcium level. These effects of 1,24(OH)2D3 were similar to, or rather more than, those of physiologically active 1,25(OH)2D3. However, 1,24(OH)2D3 was found to cause less hypercalcemia than 1,25(OH)2D3 when administrated intravenously to rats, suggesting its possible therapeutic value in psoriasis.

Topics: Animals; Cell Differentiation; Cells, Cultured; Dihydroxycholecalciferols; Humans; Hypercalcemia; Keratinocytes; Psoriasis; Rats; Receptors, Calcitriol; Receptors, Steroid

Topics: Animals; Dihydroxycholecalciferols; Female; Guinea Pigs; Petrolatum; Psoriasis

We treated 11 psoriatic patients with topical 1 alpha,24-dihydroxycholecalciferol, a new synthetic analogue of active vitamin D3. In 10 of 15 tests the lesions cleared completely within 1-4 weeks, although some relapses occurred shortly after cessation of treatment. There were no side-effects. We suggest that 1 alpha, 24(OH)2D3 merits further investigation as a potentially useful topical therapy for psoriasis.

Topics: Adolescent; Adult; Aged; Dihydroxycholecalciferols; Female; Humans; Male; Middle Aged; Ointments; Psoriasis