Combination of tacalcitol ointment and photodynamic therapy for the treatment of follicular mucinosis of the scalp.

Follicular mucinosis (FM) is a rare inflammatory disorder histologically characterized by mucin deposition in the follicular epithelium. There is no standard therapy for FM and several treatments have been described in the literature. We present the case of a 59 year-old female affected by a recalcitrant FM with diffuse scalp alopecia, in which complete clinical remission was achieved after a combination of topical tacalcitol and photodynamic therapy.

Hailey-Hailey disease successfully treated with vitamin D oral supplementation.

Hailey-Hailey disease (HHD) also known as familial benign chronic pemphigus is a rare autosomal dominant genodermatosis. HHD treatment is often not satisfactory and hence, various modalities of treatment have been tried. We describe the case of a 37-year-old woman with a 2 years history of macerated erythematous plaques along with erosions, fissures, and crusts located on axillae and submammary areas, successfully treated with only oral supplementation of vitamin D (800 I.U./die) for 3 months. We reported this case to suggest that oral vitamin D may be enumerated in the various treatments proposed for HHD so far due to its rapid efficacy on skin lesions and symptoms.

1, 25-dihidroxivitamina-D 3 sobre as características ósseas de frangos de corte fêmeas / 1, 25-dihydroxyvitamin-D3 over bony characteristics of female broilers

Objetivou-se avaliar as características dos tibiotarsos de frangos de corte fêmeas. As variáveis analisadas foram os pesos in natura, secos e desengordurados, o comprimento, os diâmetros, a resistência óssea, o índice de Seedor (IS), os percentuais de proteínas colagenosas (PC), as proteínas não colagenosas (PNC), os minerais (cálcio, fósforo, potássio e sódio) e as cinzas. Foram utilizadas 648 aves, da marca comercial Cobb®, em um delineamento em blocos ao acaso, com seis tratamentos e seis repetições, com 18 aves por unidade experimental. Os tratamentos consistiram na suplementação de 0,00; 0,50; 1,00; 1,50; 2,00 e 2,50 µg de 1,25-dihidroxivitamina-D3 (1,25(OH)2D3)/kg de ração. Aos 21 e 35 dias de idade, as aves foram pesadas e uma ave por unidade experimental (UE) com o peso médio da UE foi eutanasiada para a obtenção dos tibiotarsos e subsequente análise dos parâmetros ósseos. As variáveis métricas, bem como a composição orgânica (PC), a densidade (IS) e a resistência à quebra dos ossos das aves, não foram influenciadas pelos tratamentos. No recebimento de 2,50 µg de 1,25(OH)2D3/kg de ração, observou-se maior retenção mineral (cinzas) nos ossos das aves aos 35 dias de idade.(AU)

This study aimed to evaluate the characteristics of tibiotarsus of female broilers. The variables analyzed were the weights in natura, dry and degreased, length, diameter, bone strength, Seedor index, percentage of collagenous protein (CP), non-collagenous proteins (NCP), minerals (calcium, phosphorus, potassium and sodium), and ash. Six hundred forty-eight, Cobb® birds were used, a design of randomized blocks with six treatments and six replicates of 18 birds each. The treatments consisted of supplementation of 0.00; 0.50; 1.00; 1.50; 2.00 to 2.50 µg of 1,25-dihydroxyvitamin-D3 (1,25(OH)2D3)/kg of ration. At 21 and 35 days of age the birds were weighed and a unit/experimental unit (EU) with the EU average weight was euthanized to obtain the tibiotarsos and subsequent analysis of the bone parameters. The metric variables, as well as the organic composition (CP), density (IS) and resistance to breakage of the bones of the birds were not affected by treatments. Upon reception of 2.50 µg of 1,25(OH)2D3/kg ration, there was a higher mineral retention (ashes) in the bones of female broilers at 35 days of age.(AU)

Effect of narrow band ultraviolet B phototherapy as monotherapy or combination therapy for vitiligo: a meta-analysis.

BACKGROUND: The treatment of vitiligo is still one of the most difficult dermatological challenges, although there are many therapeutic options. Narrow band ultraviolet B (NB-UVB) phototherapy is considered to be a very important modality for generalized vitiligo. OBJECTIVE: The aim of this study was to explore whether a combination of NB-UVB and topical agents would be superior to NB-UVB alone for treating vitiligo. METHODS: We searched the electronic databases such as PUBMED, EMBASE, Cochrane Library, and Web of Science. The primary outcome was the proportion of ≥50% repigmentation (a clinical significance), and secondary outcome was the proportion of ≥75% repigmentation (an excellent response). RESULTS: Seven randomized controlled trials (RCTs) involving 240 patients (413 lesions) were included in this meta-analysis. The study showed no significant difference between NB-UVB combination therapy (NB-UVB and topical calcineurin inhibitor or vitamin D analogs) and NB-UVB monotherapy in the outcomes of ≥50% repigmentation and ≥75% repigmentation. However, lesions located on the face and neck had better results in ≥50% repigmentation (RR = 1.40, 95% CI 1.08-1.81) and ≥75% repigmentation (RR = 1.88, 95% CI 1.10-3.20) with NB-UVB and topical calcineurin inhibitor combination therapy vs. NB-UVB monotherapy. CONCLUSIONS: The meta-analysis suggested that adding neither topical calcineurin inhibitors nor topical vitamin-D3 analogs on NB-UVB can yield significantly superior outcomes than NB-UVB monotherapy for treatment of vitiligo. However, addition of topical calcineurin inhibitors to NB-UVB may increase treatment outcomes in vitiligo affecting face and neck.

Tacalcitol: a useful adjunct to narrow-band ultraviolet-B phototherapy in vitiligo.

BACKGROUND: Phototherapy especially narrow-band UV-B (NBUVB) has been considered as mainstay of therapy in nonsegmental vitiligo (generalized type). Topical tacalcitol has also been claimed to be effective, either as monotherapy or as combination therapy. PURPOSE: Comparison of clinical efficacy and safety of NBUVB in combination with topical tacalcitol vs. NBUVB alone in vitiligo. MATERIAL & METHODS: Thirty patients with symmetrical vitiliginous lesions were enrolled for 24 weeks. Patients were instructed to apply tacalcitol ointment on right side of body once daily. In addition, the whole body was irradiated with NBUVB thrice weekly. All the patients were examined, and lesional photography was done. Patients were also followed up for 6 months post-treatment. RESULTS: Our study resulted in two key findings: (1) There was a statistically significant difference in mean percentage of repigmentation at 8, 16 and 24 weeks between combination therapy and NBUVB. (2) The mean cumulative dose and number of treatment sessions for initial repigmentation were significantly lower with combination therapy. No serious adverse effects were observed during the study period. CONCLUSION: Topical tacalcitol potentiates efficacy of NBUVB as it enhances extent of pigmentation, decrease time to repigmentation and lowers the cumulative doses of NBUVB, thereby leading to greater patient satisfaction and improved compliance.

Vitamin D analogs combined with 5-fluorouracil in human HT-29 colon cancer treatment.

In the present study, we evaluated the antitumor effect of two synthetic analogs of vitamin D, namely PRI-2191 [(24R)-1,24-dihydroxyvitamin D3] and PRI-2205 (5,6-trans calcipotriol), in combined human colon HT-29 cancer treatment with 5-fluorouracil (5-FU). Mice bearing HT-29 tumors transplanted subcutaneously or orthotopically were injected with vitamin D analogs and 5-FU in various schedules. A statistically significant inhibition of subcutaneous or orthotopic tumor growth was observed as a result of combined therapy. In HT-29 tumors and in cells from in vitro culture, we observed increased vitamin D receptor (VDR) expression after treatment with either PRI-2205 or 5-FU alone, or in combination. Moreover, PRI-2205 decreased the percentage of cells from intestinal tumors in G2/M and S stages and increased sub-G1. Increased VDR expression was also observed after combined treatment of mice with 5-FU and PRI-2191. Moreover, our docking studies showed that PRI-2205 has stronger affinity for VDR, DBP and CAR/RXR ligand binding domains than PRI-2191. PRI-2191 analog, used with 5-FU, increased the percentage of subcutaneous tumor cells in G0/G1 and decreased the percentage in G2/M, S and sub-G1 populations as compared to 5-FU alone. In in vitro studies, we observed increased expression of p21 and p-ERK1/2 diminution via use of both analogs as compared to use of 5-FU alone. Simultaneously, PRI-2191 antagonizes some pro-apoptotic activities of 5-FU in vitro. However, in spite of these disadvantageous effects in terms of apoptosis, the therapeutic effect expressed as tumor growth retardation by PRI-2191 is significant. Our results suggest that the mechanism of potentiation of 5-FU antitumor action by both analogs is realized via increased p21 expression and decreased p-ERK1/2 level which may lead to diminution of thymidylate synthase expression. Higher binding affinity for VDR, DBP, but also for CAR\RXR ligand binding domain of PRI-2205 may, in part, explain its very low toxicity with sustained anticancer activity.

Combined colonic cancer treatment with vitamin D analogs and irinotecan or oxaliplatin.

UNLABELLED: aim: The aim of this study was the evaluation of the antitumor effect of two synthetic analogs of vitamin D, PRI-2191 and PRI-2205 in combined treatment with irinotecan or oxaliplatin on mouse (MC38) and human (HT-29) colon cancer cells. MATERIALS AND METHODS: Mice bearing subcutaneous tumors were injected with vitamin D analogs and with irinotecan or oxaliplatin, according to various schedules. RESULTS: Statistically significant inhibition of MC38 tumor growth by combined therapy was observed. When analogs were used in combined treatment with irinotecan, survival times of mice were significantly prolonged. We also observed improved antitumor effects in combined treatment with oxaliplatin in mice bearing HT-29 tumors, however, antagonism in life span prolongation was observed. Analog PRI-2191 increased the expression of vitamin D receptor (VDR), retinoic X receptor-α (RXRα) and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK1/2) in HT-29 tumors when used alone. VDR and RXRα expressions were up-regulated by PRI-2191 analog, as compared to oxaliplatin alone. CONCLUSION: The obtained results suggest that vitamin D analogs could be used in combined colonic cancer treatment with irinotecan or oxaliplatin. However, the regulation of ERK1/2 expression by both analogs and oxaliplatin may explain the observed antagonistic interactions.

Vitamin D analogs decrease in vitro secretion of RANTES and enhance the effect of budesonide.

PURPOSE: Eosinophils appear to be central inflammatory cells in the pathogenesis of rhinosinusitis with nasal polyps (NP). One of the most predominantly recognized eosinophil chemoattractants is RANTES. The aim of this study was to assess the influence of vitamin D (VD) derivates on RANTES expression in the culture of nasal polyp fibroblasts. MATERIAL AND METHODS: NP fibroblast cell cultures derived from 16 patients with NP were first stimulated with bacterial LPS and than incubated in increasing concentrations (from 10(-7)M to 10(-4)M) of calcitriol, tacalcitol or budesonide and in combination with one of VD derivate with budesonide in 1:1, 1:3 and 3:1 ratios. Quantitative analysis of RANTES level was conducted in culture supernatants using an ELISA method. RESULTS: The highest calcitriol concentration (10(-4)M) as well as tacalcitol at 10(-5)M and 10(-4)M reduced RANTES production significantly compared to the control (201.1pg/ml, 338.7pg/ml, 211.3pg/ml v 571.78pg/ml; p<0.05). Budesonide and calcitriol administered in 1:3 ratio and budesonide and tacalcitol in 1:1 and 1:3 reduced RANTES concentration significantly better than each of the drug used in monotherapy (p<0.05). Budesonide and tacalcitol in 1:1 and 1:3 ratios suppressed RANTES production to the lowest level (171.8±97.6pg/ml and 178.7±105.22pg/ml, respectively). CONCLUSION: Active VD compounds via downregulation of RANTES production exert a potential role as a complementary element in the therapy of chronic rhinosinusitis with NP. Compounds consisting of budesonide and VD derivate have an advantage over both drugs used in monotherapy.

Topical vitamin D3 analogues induce thymic stromal lymphopoietin and cathelicidin in psoriatic skin lesions.

BACKGROUND: 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. OBJECTIVES: To clarify whether topical VD3As induce TSLP and cathelicidin, and to examine the modulation of expression patterns of related cytokines in human psoriatic lesions. METHODS: 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. RESULTS: 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-1ß 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. CONCLUSIONS: Topical VD3As induce TSLP and cathelicidin in psoriatic lesions, resulting in suppression of IL-12/23 p40, IL-1α, IL-1ß and TNF-α, thereby ameliorating psoriatic plaques.

The in-vitro antiproliferative effect of PRI-2191 and imatinib applied in combined treatment with cisplatin, idarubicin, or docetaxel on human leukemia cells.

Imatinib mesylate (Gleevec, STI571) is a specific inhibitor of the Bcr/Abl fusion tyrosine kinase that exhibits potent antileukemic effects in chronic myelogenous leukemia. Bcr/Abl-positive K562 and Bcr/Abl-negative HL-60 human leukemia cells were used to investigate the effect of PRI-2191, a calcitriol analog, on the biological effects of imatinib combined with other anticancer drugs. The results show that PRI-2191 enhances the antiproliferative effect of imatinib on HL-60 cells. When these two agents together are applied with either docetaxel or cisplatin, but not with idarubicin, the antiproliferative effect could still be enhanced. Moreover, when the interaction between the chemotherapy agents was antagonistic or additive, PRI-2191 could even shift it to synergism. This effect correlated with an accumulation of HL-60 cells in the G0/G1 phase of the cell cycle and a decrease in the percentage of cells in the G2/M and S stage in the ternary combinations used. PRI-2191 did not influence apoptosis induced by imatinib alone or in ternary combinations with all the chemotherapy agents used. These results may suggest that the stronger antiproliferative effect of the combined treatment with PRI-2191 on HL-60 cells is related to cell cycle arrest rather than to the induction of apoptosis.

The separate daily application of tacalcitol 4 µg/g ointment and budesonide 0.25 mg/g cream is more effective than the single daily application of a two compound ointment containing calcipotriol 50 µg/g and betamethasone dipropionate 0.5 mg/g.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Childhood psoriasis treatment: evidence published over the last 5 years.

Psoriasis is a common skin condition seen in pediatrics. Treatment modalities used to treat psoriasis in children are different from those prevailing in the adult population and require adequate testing in pediatric subjects. This article reviews the published evidence on the different treatment modalities for pediatric psoriasis over the past 5 years.

Successful treatment of lichen spinulosus with topical tacalcitol cream.

Lichen spinulosus (LS) is a rare idiopathic cutaneous eruption characterized by follicular keratotic spiny papules that are grouped in large patches. Here, we report two cases of LS in the submental area, an uncommon site, which were treated effectively and safely with topical tacalcitol cream.

High-concentration (20 µg g⁻¹ ) tacalcitol ointment in the treatment of facial psoriasis: an 8-week open-label clinical trial.

BACKGROUND: 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. OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Biopsy proven morphea treated with tacalcitol ointment: case report.

A 43-year-old woman presented with a widespread morphea, which had its onset three months before. The patient had several plaques of active, pigmented, lilac halo disease on the trunk, arms and thighs. A biopsy confirmed that the patient was suffering from morphea. Therapy with clobetasol propionate ointment 0.05% was introduced, applied twice a day, 5 days a week. After a month, the ointment failed to significantly improve the lesions. Then the patient was treated with clobetasol ointment in the morning and tacalcitol ointment 4 mcg/g in the evening. This combination resulted in marked improvement of the disease after 20 days of therapy, and we decided to stop topical steroid. After three months of treatment with topical tacalcitol once a day, the plaques regressed considerably and only a very slight pigmentation remained. Therapy was further reduced to one evening, every other day for six months more, and then was suspended completely. No side effects were observed and there was no recurrence at 24-month follow up.