maxacalcitol and Psoriasis

A little over two decades ago, the vitamin D activation pathway was elucidated and alfacalcidol arrived on the scene as a prodrug for active vitamin D, 1,25-dihydroxyvitamin D(3), to remedy vitamin D deficiency. With the concurrent reported discovery of the differentiation-inducing effect of active vitamin D, its diverse physiological effects have become appreciated and the research aiming to accentuate selected physiological effects by analog research has made a fresh development. Our studies aimed particularly at separating the differentiation-inducing effect/cell growth-inhibitory effect and the calcemic effect of active vitamin D led to the development of two characteristic analogs, OCT and ED-71. OCT, characterized by its profound differentiation-inducing effect and modest calcemic effect, is currently in practical use as an injectable therapeutic agent for secondary hyperparathyroidism as well as in clinical settings as an ointment for the treatment of psoriasis vulgaris. The other analog, ED-71, possesses a profile inverse to that of OCT and is now under clinical development as an oral preparation for treatment of osteoporosis. The present overview refers to methodology of searching next-generation analogs, exemplifying a new analog, DD-281, based on the knowledge accumulated through development of OCT and ED-71.

Topics: Animals; Calcitriol; Cell Differentiation; Cell Division; Dosage Forms; Drug Design; Humans; Hyperparathyroidism, Secondary; Osteoporosis; Psoriasis; Receptors, Calcitriol; Vitamin D

Maxacalcitol (Oxarol) is a derivative of vitamin D compounds applied for the secondary hyperparathyroidism (2 degrees HPT) of hemodialysis (HD) patients as an injection and psoriasis as an ointment. 2 degrees HPT is one of the complications in HD patients with hyperplasia of parathyroid glands and elevated serum parathyroid hormone (PTH) levels. On the other hand, vitamin D compounds are known to have multiple actions in many organs (promotion of calcium absorption from the small intestine, induction of differentiation of leukemia cells, differentiation and proliferation of the chondrocyte, muscle cells and epidermal cells, immunosuppressive activities) and their activities on parathyroid glands seem to be mediated by the vitamin D receptor (genomic action). It was reported that both serum PTH and PTH mRNA levels were suppressed by Maxacalcitol with less calcemic action and also Maxacalcitol could ameliorate high-turnover bone and marked osteitis fibrosa in uremic rats. Here I review many reports focused on the effects of Maxacalcitol on the 2 degrees HPT.

Topics: Animals; Bone and Bones; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Clinical Trials, Phase III as Topic; Dosage Forms; Humans; Hyperparathyroidism, Secondary; Parathyroid Hormone; Psoriasis; Rats; Receptors, Calcitriol

In conclusion, a number vitamin D analogues have been developed that have very low calcemic activity but retain several other properties of 1,25-(OH)2D3, including the ability to differentiate leukemia and skin cells, to enhance the immune response, and to suppress parathyroid hormone levels. Although the mechanism of this selective activity is not yet clear, these analogues may provide new insights into the differences in action of 1,25-(OH)2D3 in various target tissues. Most importantly, the selective action of these analogues may be exploited for the treatment of diseases such as leukemia, psoriasis and hyperparathyroidism.

Topics: Animals; Antineoplastic Agents; Calcitriol; Humans; Hyperparathyroidism; Leukemia; Psoriasis; Structure-Activity Relationship

Vitamin D3 ointment and corticosteroid ointment are both used for the treatment of palmoplantar pustulosis (PPP). However, to date there is no systematic study of the efficacy of combination therapy for the treatment of PPP.. We compared the efficacy of a topical combination therapy with vitamin D3 and a topical corticosteroid with that of topical corticosteroid alone in the treatment of PPP.. We evaluated left-right comparison study of the efficacy of a combination therapy consisting of maxacalcitol ointment and betamethasone butyrate propionate ointment (BBP), and monotherapy with BBP alone in 27 patients with PPP for 8 weeks.. The improvement in the symptom (erythema, pustules/vesicles, hyperkeratosis/scales) scores was high for the combination therapy. In particular, the improvement rate for pustules/vesicles at week 8 after the combination therapy was significantly higher than for the monotherapy (p < 0.05).. This combination regimen demonstrated that not only topical corticosteroids, but also topical vitamin D3 ointment, is useful for the treatment of PPP.

Topics: Administration, Topical; Adult; Aged; Calcitriol; Dermatologic Agents; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Male; Middle Aged; Ointments; Prospective Studies; Psoriasis; Skin Diseases, Vesiculobullous; Treatment Outcome

Palmoplantar pustulosis (PPP) often shows resistance to treatment. Vitamin D3 analog (VitD3 ) has been widely used for the treatment of psoriasis, however, the efficacy and safety of topical VitD3 treatment of PPP are not fully confirmed. Maxacalcitol topical ointment (22-oxacalcitriol [OCT]) was applied twice daily for 8 weeks. Evaluation of efficacy was based on scored skin findings for three main symptoms (erythema, pustules/vesicles and keratinization/scales). The primary and secondary end-points were the total and symptom-specific scores of skin findings, respectively. A total of 188 patients with moderate or severe PPP were enrolled in the study and were randomized into either the OCT group (n = 95) or placebo group (n = 93). The total scores (mean ± standard error) of skin findings at the last observation adjusting for those on day 1 were 5.0 ± 0.20 in the OCT group and 6.9 ± 0.20 in the placebo group. There was a significant decrease in the total score of skin findings in the OCT group compared with the placebo group (P < 0.0001). In particular, the score of pustules/vesicles drastically decreased in the OCT group. In terms of safety, the incidence of adverse reactions in the OCT and placebo groups were 11.6% and 9.7%, respectively. These results indicate that OCT is effective and highly safe in the management of PPP. Topical OCT treatment was found to show a potent action on pustules/vesicles thereby contributing to the cure of PPP.

Topics: Adult; Aged; Calcitriol; Dermatologic Agents; Double-Blind Method; Female; Humans; Male; Middle Aged; Ointments; Psoriasis; Treatment Outcome; Young Adult

Adalimumab is a biologic that is very effective for treatment of psoriasis. However, recalcitrant or recurrent lesions sometimes occur during treatment. Maxacalcitol is an active vitamin D3 ointment that is effective in treatment of psoriasis. Topical therapy may be beneficial in treatment of recalcitrant or recurrent lesions during treatment with systemic therapy, but there is little evidence on this topic. We investigated the effect of maxacalcitol on skin lesions during treatment with adalimumab in patients with psoriasis. Twelve patients with psoriasis were randomly assigned to two groups after informed consent - treatment with adalimumab only (n = 6), and treatment with adalimumab and maxacalcitol (n = 6) - and they were evaluated every 4 weeks for 44 weeks. Exacerbation was defined as an increase of the Psoriasis Area and Severity Index (PASI) score. The interval between adalimumab treatments was elongated to 3-4 weeks from 2 weeks according to the individual patient's condition. The PASI score was evaluated every 4 weeks, and the frequency of exacerbations was counted. The overall improvement in PASI score was not statistically different between the two groups, but the frequency of exacerbations was significantly less in the maxacalcitol combination group compared with the adalimumab monotherapy group (Mann-Whitney U-test, P < 0.05). The better control of skin lesions in patients who elongated the interval of adalimumab administration was achieved in the maxacalcitol combination group compared with the adalimumab monotherapy group. Topical maxacalcitol treatment is effective and useful in controlling skin lesions in patients with psoriasis when used in combination with adalimumab.

Topics: Adalimumab; Adult; Anti-Inflammatory Agents; Calcitriol; Dermatologic Agents; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Ointments; Psoriasis

Topical treatment with betamethasone butyrate propionate lotion on 37 patients with scalp psoriasis was replaced with a combination therapy using maxacalcitol lotion (on weekdays) and BBP (on the weekends). This combination therapy was later switched to MXA monotherapy. To identify the optimum duration of the combination therapy, the patients were divided into two groups: a 4-week group and an 8-week group, which were given combination therapy and monotherapy. In both groups, the total mean scores for the skin symptoms had significantly improved in comparison with that obtained at the outset of the study (p < 0.01). In terms of overall improvement, 20.0% of the 4-week group and 72.7% of the 8-week group yielded scores reflecting moderate or greater improvement. The treatment administered to the 8-week group was significantly more effective than that given to the 4-week group at the end of the trial (p < 0.01). This study also suggests that a 4-week combination therapy is an option before switching to monotherapy, but that an 8-week therapy is preferable in severe cases.

Topics: Administration, Cutaneous; Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Betamethasone; Calcitriol; Dermatologic Agents; Drug Administration Schedule; Drug Combinations; Drug Substitution; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Psoriasis; Scalp Dermatoses; Skin Cream

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

Combining phototherapy with topical vitamin D3 analogues is a useful therapy for the treatment of psoriasis by reducing the cumulative UV dose required for clearance of lesions. Experimental investigations demonstrated that calcipotriol is degraded by UV radiation, and suggested that calcipotriol should be applied after phototherapy but not immediately before.. Calcipotriol or maxacalcitol ointment was topically applied to psoriatic plaques of six patients immediately before or after phototherapy on the right or left side of the body, respectively.. Topical application of vitamin D3 analogues either before or after irradiation by psoralen and UVA radiation (PUVA) or narrow-band (NB)-UVB showed exactly similar effects in all patients.. Therapeutic effects of vitamin D3 analogues are not clinically inactivated by subsequent irradiation with PUVA or NB-UVB phototherapy.

Topics: Administration, Cutaneous; Adult; Calcitriol; Cholecalciferol; Combined Modality Therapy; Dermatologic Agents; Female; Humans; Male; Middle Aged; Prospective Studies; Psoriasis; Severity of Illness Index; Treatment Outcome; Ultraviolet Therapy

1alpha, 25-Dihydroxy-22-oxacalcitriol (maxacalcitol) is a vitamin D3 analogue which displays approximately 10 times greater efficacy at suppressing keratinocyte proliferation in vitro than calcipotriol and tacalcitol. To determine clinical efficacy, a phase II double-blind, randomized, left vs. right, concentration-response study was performed with once-daily topical maxacalcitol in patients with mild to moderate chronic plaque psoriasis. Primary efficacy parameters were psoriasis severity index (PSI) based on sum of scores for erythema, scaling and induration and investigators' overall assessment of patients' response to therapy at 8 weeks of treatment. One hundred and forty-four patients participated. All concentrations of maxacalcitol ointment (6, 12.5, 25 and 50 microg/g) were significantly more effective at reducing PSI than placebo (P < 0.01), with greatest effect noted for maxacalcitol 25 microg/g. Calcipotriol ointment 50 microg/g once daily as active comparator had a similar effect. Marked improvement or clearance of psoriasis was greatest for maxacalcitol 25 microg/g (55% of subjects) which compared favourably with calcipotriol (46%). Improvement continued throughout the study period, with no plateau at week 8. Investigators' and patients' side preference (secondary efficacy parameters) rated maxacalcitol more effective than placebo and 25 microg/g maxacalcitol better than calcipotriol (P < 0.05 for investigators' assessment). Twelve patients withdrew from the study due to adverse events, of which four were judged to be due to study medication. This study indicates that once-daily maxacalcitol ointment is effective in the management of plaque psoriasis, with greatest effect noted at 25 microg/g. As no response plateau was noted at 8 weeks, these data suggest that further benefit might be obtained if maxacalcitol ointment were applied for longer. Finally, investigators' overall assessment and side preference suggest that maxacalcitol 25 microg/g may be more effective than once-daily calcipotriol.

Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Calcitriol; Dermatologic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Eruptions; Female; Humans; Male; Middle Aged; Ointments; Psoriasis; Treatment Outcome

Aluminum precipitates have long been used as adjuvants for human vaccines, but there is a clear need for safer and more effective adjuvants. Here we report in a mouse model that the psoriasis drug Oxarol ointment is a highly effective vaccine adjuvant. By applying Oxarol ointment onto skin, humoral responses and germinal center (GC) reactions were augmented, and the treated mice were protected from death caused by influenza virus infection. Keratinocyte-specific vitamin D3 receptor (Vdr) gene expression was required for these responses through induction of the thymic stromal lymphopoietin (Tslp) gene. Experiments involving administration of recombinant TSLP or, conversely, anti-TSLP antibody demonstrated that TSLP plays a key role in the GC reactions. Furthermore, cell-type-specific Tslpr gene deletion or diphtheria toxin-mediated deletion of specific cell types revealed that CD11c+ cells excluding Langerhans cells were responsible for the Oxarol-mediated GC reactions. These results indicate that active vitamin D3 is able to enhance the humoral response via Tslp induction in the skin and serves as a new vaccine adjuvant.

Topics: Animals; Calcitriol; Dermatologic Agents; Drug Repositioning; Influenza Vaccines; Mice; Mice, Inbred C57BL; Mice, Transgenic; Ointments; Psoriasis

In general, chronotherapy is desirable for a more effective and/or safe dosage regimen. In this study, a daily rhythm of skin vitamin D receptor (VDR) and chronotherapeutic profiles of maxacalcitol, a vitamin D analogue, were evaluated using mice with skin inflammation induced by topical 12-O-tetradecanoylphorbol-13-acetate (TPA). This study showed that skin nuclear VDR expression in TPA-treated mice has a daily rhythm with the peak at the middle of active period. The effects of maxacalcitol were greater after dosing during early to middle of active period than those after dosing during early to middle of inactive period. These data suggest that chronotherapeutic profiles of maxacalcitol partly depend on the daily rhythm of skin nuclear VDR in TPA-treated mice. Because TPA-treated mice are considered as one of animal models of psoriasis, these animal data might be helpful for establishing chronotherapeutic approach of maxacalcitol in clinical practice.

Topics: Animals; Calcitriol; Chronotherapy; Circadian Rhythm; Inflammation; Male; Mice; Mice, Inbred C57BL; Psoriasis; Receptors, Calcitriol; Skin; Tetradecanoylphorbol Acetate

Psoriasis is a Th1/Th17-mediated inflammatory dermatosis treated with topical corticosteroids and vitamin D. To compare the effects of a VD3 A maxacalcitol and betamethasone valerate (BV) steroid lotion on topical imiquimod (IMQ)-induced psoriasiform skin inflammation.. Female BALB/c mice were treated with vehicle, maxacalcitol or BV lotion on the skin for 3 days, and IMQ cream for 6 days. q-PCR, H&E, immunohistochemistry and immunofluorescence studies were performed on skin samples. Additionally, mice were treated with vehicle, maxacalcitol or BV lotion for 3 days and CD4. Maxacalcitol and BV were comparable in regards clinical improvement, although maxacalcitol reduced the MHC Class II. These results indicate that maxacalcitol reduces psoriasiform skin inflammation by inducing Treg cells as well as downregulating IL-23 and IL-17 production.

Topics: Adoptive Transfer; Animals; Betamethasone Valerate; Calcitriol; Dermatologic Agents; Down-Regulation; Female; Humans; Imiquimod; Interleukin-17; Interleukin-23; Mice; Mice, Inbred BALB C; Psoriasis; Skin; T-Lymphocytes, Regulatory; Treatment Outcome

Topics: Administration, Topical; Animals; Calcitriol; Dermatologic Agents; Dog Diseases; Dogs; Humans; Male; Middle Aged; Psoriasis; Renal Insufficiency; Severity of Illness Index

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

Topics: Administration, Cutaneous; Calcitriol; Dermatologic Agents; Humans; Infant; Male; Psoriasis; Recurrence; Treatment Outcome

The remission period of psoriasis vulgaris following narrowband ultraviolet B (NB-UVB) light therapy with topical vitamin D(3) application was evaluated retrospectively to investigate the therapeutic efficacy. Fifty-two patients (60 cases) were treated with a 5-day/week protocol of NB-UVB light irradiation plus topical vitamin D ointment application for 1 month and followed up for at least 12 months. We considered re-exacerbation as the time when the patients needed treatment other than topical therapy. The remission period was defined as the duration from the end of treatment until re-exacerbation. Twenty-seven cases (56%) of psoriasis showed a remission period longer than 12 months. The patients with a past history of systemic therapy or phototherapy had a significantly shorter remission period than those without such a history. No statistically significant differences were observed in sex, age, period before treatment, Psoriasis Area and Severity Index score and total irradiation dose. A previous history of systemic therapy or phototherapy may mean that the disease is severe and sufficiently active to form multiple new lesions requiring these treatments. Our results suggest that the 5-day/week NB-UVB light protocol for 4 weeks is an effective and safe treatment for psoriasis vulgaris and can induce long-term remission.

Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Calcitriol; Combined Modality Therapy; Dermatologic Agents; Female; Humans; Male; Middle Aged; Psoriasis; Remission Induction; Retrospective Studies; Time Factors; Treatment Outcome; Ultraviolet Therapy; Young Adult

In this study, we aimed at confirming the clinical usefulness of a supplementary additional cyclosporin microemulsion preconcentrate (CyA MEPC) administration in 15 patients with psoriasis vulgaris whose disease activity had been unchanged or exacerbated with topical maxacalcitol treatment. Each patient took a supplementary CyA MEPC administration, 2.5 mg/kg per day in addition to maxacalcitol ointment therapy. When the Psoriasis Area and Severity Index (PASI) score revealed over a 75% decrease against the initial value, the administration of CyA MEPC was tapered off, and a topical application of maxacalcitol ointment was continued for the maintenance phase. All patients could obtain improvement within 12 weeks. In 12 patients whose PASI score reduced over 75%, CyA MEPC was tapered off. Of those, five patients remained in remission by maxacalcitol ointment for over 12 months and three patients for 6 months. In conclusion, this preliminary study may suggest that supplementary therapy of short-term CyA MEPC administration in combination with topical vitamin D3 treatment may be worth trying for patients with moderate psoriasis vulgaris.

Topics: Administration, Topical; Adult; Calcitriol; Cyclosporine; Dermatologic Agents; Drug Synergism; Female; Humans; Male; Ointments; Patient Satisfaction; Psoriasis; Remission Induction

Topics: Acute Disease; Aged; Calcitriol; Dermatologic Agents; Humans; Male; Ointments; Pancreatitis; Psoriasis

Design, synthesis, and in vitro and in vivo evaluation of a series of antipsoriatic antedrugs having 16-en-22-oxa-vitamin D3 are described. Among the seven compounds examined, two are promising: ester 5c and amide 5f, both of which exhibit greater potent antiproliferation activity with lessened calcemic activity than the presently prescribed maxacalcitol (2).

Topics: Animals; Cholecalciferol; Drug Design; Molecular Structure; Psoriasis; Rats; Structure-Activity Relationship

Topics: Administration, Topical; Calcitriol; Combined Modality Therapy; Dermatologic Agents; Humans; Psoriasis; Ultraviolet Therapy

Combination treatment with topical vitamin D(3) and narrow-band ultraviolet B (UVB) radiation is effective against psoriasis vulgaris. We compared the efficacy of the topical vitamin D(3) derivatives calcipotriol and maxacalcitol in combination therapy.. In this retrospective observational study, 21 patients admitted to Nagoya City University Hospital between April 2001 and September 2004 were enrolled.. Combination treatment with calcipotriol or maxacalcitol and narrow-band UVB was effective against psoriasis vulgaris. Calcipotriol induced a more rapid improvement and required lower levels of narrow-band UVB irradiation to be effective. Serum calcium levels were slightly increased after 4 weeks of treatment, but there was no significant difference between the two groups. No other adverse effects were observed in either of the two groups.. The findings of this retrospective observational study indicated that combination treatment with topical vitamin D(3) derivatives and narrow-band UVB is effective against psoriasis without any obvious side-effects. These findings provide further evidence that calcipotriol has advantages over maxacalcitol regarding the narrow-band UVB-accumulated treatment dose and improvement rate of psoriasis area and severity index (PASI) scores.

Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Calcitriol; Combined Modality Therapy; Dermatologic Agents; Female; Hospitals, University; Humans; Japan; Male; Middle Aged; Psoriasis; Retrospective Studies; Severity of Illness Index; Treatment Outcome; Ultraviolet Therapy

Vitamin D has been used for topical treatment of psoriasis, and 22-oxacalcitriol (OCT), shown to be less calcemic, was developed for the topical treatment of psoriasis in Japan. Recently, we treated a psoriatic patient with diabetic nephropathy who developed severe hypercalcemia with exacerbation of chronic renal failure by the use of topical OCT. Analysis of the reported cases demonstrated that both the severity of psoriasis and renal dysfunction are critical factors in the induction of hypercalcemia in the topical treatment of psoriasis. Therefore, we must pay attention to the severity of psoriasis, especially when complicated by renal function impairment. Regular monitoring of Ca and renal function is essential to avoid life-threatening hypercalcemia from the topical treatment with vitamin D analogues.

Topics: Calcitriol; Dermatologic Agents; Diabetic Nephropathies; Humans; Hypercalcemia; Kidney Failure, Chronic; Male; Middle Aged; Psoriasis

Recently, there have been many vitamin D3 analogues synthesized and tried in the treatment of psoriasis. In the experiments reported here we observed and compared their effects on normal and psoriatic epidermis in organ culture in vitro. We employed a new vitamin D3 analogue, 22-oxa-calcitriol (OCT), the effect of which was compared with that of calcitriol (1,25-D3). Both caused suppression of proliferation of normal and psoriatic epidermis, dependent upon concentration and culture time. Histologically, in the presence of the agents, degeneration started from the top of the epidermis downwards. This is the first report of cell degeneration as a direct effect of vitamin D. The nature of the degeneration was evaluated by electron microscopy (EM) and by the in situ nick end labeling technique (TUNEL), and these studies revealed that the degeneration involved necrosis rather than apoptosis. This in vitro method may be useful to assess the effectiveness of newly synthesized vitamin D3 analogues in the treatment of psoriasis.

Topics: Apoptosis; Bromodeoxyuridine; Calcitriol; Cholecalciferol; Dermatologic Agents; Dose-Response Relationship, Drug; Epidermis; Humans; Microscopy, Electron; Organ Culture Techniques; Psoriasis