Tacalcitol 4micrograms/g ointment

Darier's disease (also known as keratosis follicularis or dyskeratosis follicularis) is an autosomal dominant inherited disorder which manifests as hyperkeratotic greasy papules in the first or second decade of life. Aside from symptom management and behavioral modifications to avoid triggers, there are currently no validated treatments for Darier's disease (DD). However, a variety of treatments have been proposed in the literature including retinoids, steroids, vitamin D analogs, photodynamic therapy, and surgical excision. The purpose of this review article is to identify therapeutic options for treating DD and to outline the evidence underlying these interventions. A search was conducted in Medline for English language articles from inception to July 4, 2020. Our search identified a total of 474 nonduplicate studies, which were screened by title and abstract. Of these, 155 full text articles were screened against inclusion/exclusion criteria, and 113 studies were included in our review. We identified Grade B evidence for the following treatments of DD: oral acitretin, oral isotretinoin, systemic Vitamin A, topical tretinoin, topical isotretinoin, topical adapalene gel, topical 5-flououracil, topical calciptriol and tacalcitol (with sunscreen), grenz ray radiation, and x-ray radiation. All other evidence for treatments of DD consisted of case reports or case series, which is considered grade C evidence. Considering the quality and quantity of evidence, clinicians may consider initiating a trial of select topical or oral retinoids first in patients with localized or generalized DD, respectively.

Abstract licence: CC BY

Lifestyle habits and insufficient sunlight exposure lead to a high prevalence of vitamin D hypovitaminosis, especially in the elderly. Recent studies suggest that in central Europe more than 50% of people over 60 years are not sufficiently supplied with vitamin D. Since vitamin D hypovitaminosis is associated with many diseases, such as Alzheimer's disease (AD), vitamin D supplementation seems to be particularly useful for this vulnerable age population. Importantly, in addition to vitamin D, several analogues are known and used for different medical purposes. These vitamin D analogues differ not only in their pharmacokinetics and binding affinity to the vitamin D receptor, but also in their potential side effects. Here, we discuss these aspects, especially those of the commonly used vitamin D analogues alfacalcidol, paricalcitol, doxercalciferol, tacalcitol, calcipotriol, and eldecalcitol. In addition to their pleiotropic effects on mechanisms relevant to AD, potential effects of vitamin D analogues on comorbidities common in the context of geriatric diseases are summarized. AD is defined as a complex neurodegenerative disease of the central nervous system and is commonly represented in the elderly population. It is usually caused by extracellular accumulation of amyloidogenic plaques, consisting of amyloid (Aβ) peptides. Furthermore, the formation of intracellular neurofibrillary tangles involving hyperphosphorylated tau proteins contributes to the pathology of AD. In conclusion, this review emphasizes the importance of an adequate vitamin D supply and discusses the specifics of administering various vitamin D analogues compared with vitamin D in geriatric patients, especially those suffering from AD.

Abstract licence: CC BY

Purpose Beyond its direct anticancer effects in breast cancer (BC), vitamin D3 (VD3) also modulates tumor progression and metastasis through immune mechanisms. T-helper 17 (Th17) cells may play a key role in these effects. This study investigates how VD3 influences Th17 differentiation in 4T1 and 67NR murine BC models. Methods Calcitriol or tacalcitol was administered to young and aged mice bearing 4T1 or 67NR tumors. Tumor growth, angiogenesis, and metastasis were evaluated. CD4+ lymphocytes isolated from tumors and other tissues were analyzed by flow cytometry for IL-17 and osteopontin (OPN, Spp1) receptors. CD4+ splenocytes were separated; gene expression was assessed using qPCR, and protein levels by Western blotting, ELISA. CD3+CD4+ splenocytes were ex vivo differentiated into Th17 cells with blockade of CD29, CD51, and CD44, followed by flow cytometric analysis of IL-17 and IFNγ expression. Results Tacalcitol increased metastasis in young mice but decreased it in aged mice with 4T1 tumors. Th17 cell levels in the lungs increased in young mice treated with tacalcitol but declined in aged counterparts. IL-17+ and IFNγ+ Th17 cells increased upon differentiation from splenocytes of treated mice. CD29 promoted IL-17 expression in tacalcitol-treated mice, while CD51 and CD44 had opposing effects. CD51 blockade reduced IFNγ+ Th17 cells in both treatment groups. Spp1 expression increased in CD4+ lymphocytes, and OPN levels were elevated in induced Th17 cells from tacalcitol-treated young mice, suggesting a role in Th17 activation. Conclusion CD29 stimulates IL-17 expression in response to tacalcitol, while CD51 and CD44 exert opposing effects. CD51 also mediates IFNγ expression. VD3-induced modulation of IL-17 and IFNγ in Th17 cells may influence their pro- or anticancer function.

Abstract licence: CC BY 4.0