Tacalcitol

Tacalcitol (1,24(R)-Dihydroxyvitamin D3; 1.alpha.,24R-Dihydroxyvitamin D3)promotes normal bone development by regulating calcium.Tacalcitol(1,24(R)-Dihydroxyvitamin D3; 1.alpha.,24R-Dihydroxyvitamin D3) modulates immunological and inflammatory processes. Tacalcitol induces nerve growth factor production in epidermal keratinocytes.

Protective effects of tacalcitol against oxidative damage in human epidermal melanocytes.[Pubmed:28074522]

Int J Dermatol. 2017 Feb;56(2):232-238.

BACKGROUND: Oxidative damage may lead to the dysfunction of melanocytes (MCs) and is one of the causative mechanisms involved in the pathogenesis of vitiligo. OBJECTIVES: This study was designed to investigate the protective effects of the vitamin D3 analog Tacalcitol on oxidative damage induced by hydrogen peroxide (H2 O2 ) in human epidermal MCs. METHODS: Human epidermal MCs were cultured and identified by l-DOPA staining and HMB-45 immunohistochemical staining. The model of oxidative damage induced by H2 O2 was established, and the cells were treated with Tacalcitol. The viability of MCs was determined using an MTS assay. Morphological changes in cell dendrites were observed by microscopy, and the rate of change of dendrites was calculated. The reactive oxygen species (ROS) level in MCs was determined using immunofluorescence microscopy. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in MCs were determined using the WST-1 and TBA methods, respectively. RESULTS: In comparison with the control group, the viability of MCs and SOD activity were significantly decreased in the H2 O2 group (P < 0.05) and significantly increased in the Tacalcitol group (P < 0.05). In comparison with the control group, the rate of change of cell dendrites and levels of ROS and MDA were significantly increased in the H2 O2 group (P < 0.05) and significantly decreased in the Tacalcitol group (P < 0.05). CONCLUSIONS: Tacalcitol can reduce oxidative damage induced by H2 O2 in MCs by inhibiting intracellular ROS overproduction, increasing SOD activity, and decreasing the level of MDA, thereby reducing cell apoptosis.

Tacalcitol in the treatment of acquired perforating collagenosis.[Pubmed:24707254]

Case Rep Dermatol. 2014 Feb 27;6(1):69-73.

Acquired perforating collagenosis (APC) is a rare perforating dermatosis characterized by transepidermal collagen elimination. We describe a 65-year-old patient, with long-standing type 2 diabetes mellitus and a 2-year history of itchy hyperkeratotic nodules situated on the back, who was subsequently diagnosed with APC. Treatment included topical corticosteroids and antihistamines, without improvement of the lesions. However, therapy with topical Tacalcitol administered for 2 months produced a significant response leading to complete remission of APC.

Tacalcitol: a useful adjunct to narrow-band ultraviolet-B phototherapy in vitiligo.[Pubmed:27552149]

Photodermatol Photoimmunol Photomed. 2016 Sep;32(5-6):262-268.

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.

Tacalcitol: A useful adjunct to narrow band ultraviolet B phototherapy in psoriasis.[Pubmed:27052200]

J Dermatolog Treat. 2016 Nov;27(6):546-551.

BACKGROUND: 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. OBJECTIVE: Comparison of the efficacy and safety of topical Tacalcitol in combination with NBUVB versus NBUVB alone in psoriasis. METHODS: 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. RESULTS: 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. CONCLUSION: Topical Tacalcitol enhances the therapeutic effects of NBUVB therapy and exerts a UVB-sparing effect, without increasing the incidence of adverse effects.

Vitamin D derivatives: calcitriol and tacalcitol inhibits interleukin-6 and interleukin-8 expression in human nasal polyp fibroblast cultures.[Pubmed:20439185]

Adv Med Sci. 2010;55(1):86-92.

PURPOSE: Biologically active vitamin D3 (VD) derivatives possess modulatory activities on immunological and inflammatory responses which can be reflected by altered levels of pro-inflammatory chemokines. Nasal polyposis (NP), defined as a chronic inflammatory process of upper respiratory system, could be influenced by VD derivatives. The purpose of this study was to investigate the influence of 1alpha,25-dihydroxyvitamin D3 (calcitriol) and 1alpha,24(R)-dihydroxyvitamin D3 (Tacalcitol) on the secretion of IL-6 and IL-8 by fibroblasts derived from NP. MATERIAL AND METHODS: The study involved 12 fibroblast cultures derived from NP samples obtained from surgically treated patients. Measurements were performed on the polyp cells after the 6-9 passages. Culture stimulation involved treatment with Tacalcitol and calcitriol at a defined strength (from 10(-7)M to 10(-4)M). IL-6 and IL-8 concentrations were estimated with ELISA. RESULTS: Treatment with calcitriol or Tacalcitol inhibits the synthesis of both IL-6 and IL-8 compared to the control group. The dose dependence of this effect has been confirmed. VD derivatives influence was marked at higher concentrations. Significant interleukin decrease was observed at 10(-5) and 10(-4) for calcitriol and 10-4 in the case of Tacalcitol. CONCLUSIONS: The present study demonstrates that calcitriol and Tacalcitol are capable of affecting pro-inflammatory cytokine (IL-6 and IL-8) levels in NP cultures. Our data imply a potential therapeutical application of topical VD derivates in NP and warrant further investigation.

Tacalcitol, an active vitamin D3, induces nerve growth factor production in human epidermal keratinocytes.[Pubmed:11464105]

Skin Pharmacol Appl Skin Physiol. 2001 Jul-Aug;14(4):226-33.

The human epidermal keratinocyte cell line K-TL-1, developed from a benign epidermal tumor, was cultured in the presence of the synthetic vitamin D3 analogue Tacalcitol [1alpha,24(R)-dihydroxyvitamin D3] to assess the effects on the production of nerve growth factor (NGF). Confluent K-TL-1 cells were cultured with 10(-8) M of Tacalcitol. Supernatants and cell homogenates were collected and NGF concentrations were determined by enzyme-linked immunosorbent assay. The concentration of NGF in the supernatants of cultures treated with Tacalcitol peaked within 24 h after the start of Tacalcitol treatment and remained stable for 96 h. This NGF induction caused by Tacalcitol was dose-dependent, showing an ED50 between 10(-10) and 10(-9) M. Induction of NGF mRNA expression by Tacalcitol was also observed by RT-PCR, indicating that Tacalcitol induced NGF expression through transcriptional activation. These results suggest that active vitamin D3 could treat peripheral neuropathy by inducing NGF production in the skin.

Tacalcitol (1,24(R)-Dihydroxyvitamin D3; 1.alpha.,24R-Dihydroxyvitamin D3) promotes normal bone development by regulating calcium.

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