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P.c.m. Van De Kerkhof - One of the best experts on this subject based on the ideXlab platform.
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wirksamkeit und sicherheit von Tacalcitol salbe in der langzeitanwendung bei chronischer plaque psoriasis
Zeitschrift für Hautkrankheiten, 2002Co-Authors: P.c.m. Van De Kerkhof, Pv Harrison, Herbert Honigsmann, J Berthjones, Cem Griffiths, R Marks, R Roelandts, E Schopf, C. TrompkeAbstract:Zusammenfassung: Da Psoriasis-Patienten haufig eine Dauertherapie benotigen, muss eine optimale Behandlung Langzeitwirksamkeit mit einem guten Sicherheitsprofil vereinen. Das Ziel der vorliegenden, multizentrischen Studie war die Beurteilung der Wirksamkeit, Sicherheit und Vertraglichkeit von Tacalcitol (4 µg/g) Salbe, bei einmal taglicher Anwendung uber einen Zeitraum von 18 Monaten. Die Beurteilung der Wirksamkeit erfolgte uber den PASI (Psoriasis Area and Severity Index) auf Grundlage der Summenscores von Rotung, Infiltration und Schuppung, sowie das Ausmas der betroffenen Korperoberflache (KOF). Zur Beurteilung der Sicherheit wurden die Serumwerte von Calcium, Parathormon, Calcitonin, 1,25-dihydroxy Vitamin-D3 (Calcitriol), sowie Urin-Calcium, Urin-Creatinin, Calcium/Creatinin Verhaltnis und α1-Microglobulin im 24-Stunden-Urin gemessen. Im ersten Teil der Studie uber drei Monate sind 304 Patienten mit chronischer Plaque Psoriasis behandelt worden, die eine betroffene Korperoberflache von 7 – 20 % aufwiesen. 257 Patienten beendeten die erste Behandlungsphase. Davon nahmen 197 Patienten an der zweiten Behandlungsphase uber 15 Monate teil. Die Tacalcitol-Therapie reduzierte erfolgreich den Schweregrad der Psoriasis und die Wirksamkeit blieb uber den gesamten Studienzeitraum erhalten. Nach dreimonatiger Therapie reduzierte sich der PASI von 9,5 auf 4,6 und betrug am Studienende nach 18 Monaten 3,25 (p < 0,0001). Gleichzeitig verringerte sich der Anteil der betroffenen Korperoberflache um 30 % nach drei Monaten und um 50 % zum Studienende. Es traten keine Hypercalcamien auf. Die Serumspiegel von Calcium, Parathormon und Calcitriol und die Laborbefunde des 24-Stunden-Urins zeigten keine signifikanten Veranderungen. Die Studie ergab keine Korrelation zwischen den Serum- oder Urinspiegeln von Calcium und der verwendeten Menge an Tacalcitol-Salbe, auch nicht bei Patienten mit grosem Salbenverbrauch (bis zu 13 g/pro Tag und bis zu 20 % KOF). Die Behandlung war sehr gut vertraglich. Es traten keine schweren oder unerwarteten Nebenwirkungen auf. Ein Abbruch der Behandlung aufgrund von Hautirritationen wurde bei 5,9 % der Patienten gesehen. Reversible lokale Hautirritationen traten meist zu Anfang der Behandlung auf, reduzierten sich aber deutlich im weiteren Therapieverlauf. Die Ergebnisse dieser Studie zeigen deutlich, dass die Tacalcitol Langzeittherapie mit einmal taglicher Anwendung, eine wirksame, sichere und gut vertragliche Therapieoption bei chronischer Plaque Psoriasis darstellt. Summary: 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 µg/g) ointment 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 24h-urine and urinary α1-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 total body involvement was 30 % at month 3 and 50 % at month 18. In no patient any relevant disturbance of calcium homeostasis was noticed. There were no significant changes in mean values of serum calcium, parathyroid hormone (PTH) 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 per day and with up to 20 % 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. In summary topical application of Tacalcitol (4 µg/g) ointment, once daily was demonstrated to be efficacious, safe and well tolerated in long-term control of plaque psoriasis.
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Influence of Tacalcitol on Cell Cycle Kinetics of Human Keratinocytes following Standardized Injury
Skin pharmacology and applied skin physiology, 1999Co-Authors: J.m. Mommers, P.e.j. Van Erp, A.c. Ter Meulen, P.c.m. Van De KerkhofAbstract:In the last few years, Tacalcitol (1α,24-dihydroxy vitamin D3, TV-02) has become widely available for the topical treatment of psoriasis. Several studies documented its effect on epidermal
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Proliferation is the main epidermal target in the treatment of psoriatic plaques with once daily application of Tacalcitol ointment.
Acta dermato-venereologica, 1999Co-Authors: F. A. C. M. Castelijns, Marie-jeanne P. Gerritsen, I.m.j.j. Van Vlijmen-willems, P.e.j. Van Erp, P.c.m. Van De KerkhofAbstract:We studied the eiect of Tacalcitol (1a,24 dihydroxy vitaminD3) ointment on clinical and immunohistochemical e⁄cacyin psoriatic patients during 2 months of treatment.The psor-iasis area and severity index decreased signi¢cantly afteronly 1 month and the total body surface index decreased55% after 2 months.To characterize the epidermal compart-ment keratin 14, keratin 16, epidermal growth factor recep-tor, apoptotic and Ki-67 positive cells were examined. After1week of treatment no signi¢cant changes were found in anyof these parameters. After 2 months, keratin 16 reached thelevels observed in normal skin and Ki-67 and keratin 14expression also reduced signi¢cantly. Epidermal growth fac-tor receptor staining and the number of apoptotic cells didnot alter during treatment. We conclude that Tacalcitol iseiective in the treatment of plaque psoriasis. Because themain epidermal eiect observed immunohistochemically is areduction in proliferation, a combination therapy usingeither corticosteroids, vitamin A derivatives or dithranolseems rational.Key words: psoriasis; epidermis; vitamin D3;immunohistochemistry.(Accepted September 23, 1998.)Acta Derm Venereol (Stockh) 1999; 79: 111^114.F. A. C. M. Castelijns, Department of Dermatology, Univer-sity Hospital of Nijmegen, PO Box 9101, NL-6500 HB Nijme-gen, The Netherlands. Email: F.Castelijns@derma.azn.nl.Tacalcitol, 1a,24-dihydroxyvitamin D3 has a well-establishede⁄cacy in the treatment of psoriasis (1, 2).The recruitment ofcyclingepidermalcellsisprofoundlyinhibitedbyTacalcitolandhyperproliferation-associated keratin 16 is markedly reducedduring Tacalcitol treatment (3).The inhibitory eiect of tacalci-tol on epidermal proliferation has also been substantiated bymeasurement of DNA content using £ow cytometry (4, 5).Involucrin, ¢laggrin and transglutaminase are also modulatedduring Tacalcitol treatment, indicating that Tacalcitol has aneiect on various phases of epidermal diierentiation (3, 6). Anin vitro study indicated that active vitamin D3 enhancesapoptosis (7).The aim of the present study was to evaluate the eiect ofTacalcitol on various characteristics of the epidermis duringtreatment of the psoriatic plaque. In particular we addressedthe following questions: to what extent are markers for earlyphenomena of psoriasis (epidermal growth factor receptor(EGFR), keratin 16), for intermediate phenomena (Ki-67antigen) and for late phenomena of psoriasis (keratin 14)aiectedbyTacalcitoltreatment?And,doesTacalcitoltreatmentresult in enhanced apoptosis?MATERIALS AND METHODS
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An update on vitamin D3 analogues in the treatment of psoriasis
Skin pharmacology and applied skin physiology, 1998Co-Authors: P.c.m. Van De KerkhofAbstract:Vitamin D3 analogues have revolutionized the topical treatment of psoriasis during the last decade. The mode of action of this ligand for the vitamin D3 receptor is via modulation of the transcription of genes with vitamin D3 response elements in their promoter region. Vitamin D3 analogues cause inhibition of various aspects of cutaneous inflammation and epidermal proliferation with enhancement of normal keratinization. In vivo, active vitamin D3 analogues proved to have a substantial antipsoriatic effect. Calcipotriol (50 micrograms/g in ointment or cream), Tacalcitol (4 micrograms/g in ointment) and calcitriol (3 micrograms/g in ointment) have been shown to have an antipsoriatic effect in placebo-controlled studies. The most extensive body of information on comparative studies and on combination therapies is available for the analogue calcipotriol. So far, calcipotriol is available as a routine treatment in most countries, whereas Tacalcitol has been registered in Japan and some European countries. From the available data in the literature we may conclude that calcipotriol is a first-line treatment for psoriasis and is advantageous in the combination with several other antipsoriatic treatments such as topical corticosteroids, PUVA, cyclosporin and acitretin. Tacalcitol 4 micrograms/g as a once-daily principle is effective in psoriasis. Comparative studies will indicate the position of the existing and new vitamin D3 analogues.
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Tacalcitol ointment in the treatment of psoriasis vulgaris a multicentre placebo controlled double blind study on efficacy and safety
British Journal of Dermatology, 1996Co-Authors: P.c.m. Van De Kerkhof, T. Werfel, Uwe-frithjof Haustein, Thomas A. Luger, B.m. Czarnetzki, R. Niemann, V PlanitzstenzelAbstract: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.
Mamoru Kiyoki - One of the best experts on this subject based on the ideXlab platform.
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Tacalcitol, an active vitamin D3, induces nerve growth factor production in human epidermal keratinocytes.
Skin pharmacology and applied skin physiology, 2001Co-Authors: Masami Fukuoka, Tomohiro Ohta, Mamoru Kiyoki, Katsutoshi Sakurai, Ichiro KatayamaAbstract: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 [1α,24(R)-dihydroxyv
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Tacalcitol (1,24(OH)2D3, TV-02) inhibits phorbol ester-induced epidermal proliferation and cutaneous inflammation, and induces epidermal differentiation in mice.
Archives of dermatological research, 1996Co-Authors: Hiroaki Sato, Tomohiro Ohta, Hiroshi Uno, Izuki Sugimoto, Takashi Matsunaga, Masahiro Tsuchimoto, Mamoru KiyokiAbstract: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.
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Tacalcitol (1,24(OH)_2D_3, TV-02) inhibits phorbol ester-induced epidermal proliferation and cutaneous inflammation, and induces epidermal differentiation in mice
Archives of Dermatological Research, 1996Co-Authors: Hiroaki Sato, Tomohiro Ohta, Izuki Sugimoto, Takashi Matsunaga, Masahiro Tsuchimoto, Mamoru KiyokiAbstract:In this study, we examined the cutaneous effects of Tacalcitol [1, 24( R )(OH)_2D_3] 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.
Hiroaki Sato - One of the best experts on this subject based on the ideXlab platform.
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Anti-inflammatory effects of Tacalcitol (1,24(R)(OH)2D3, TV-02) in the skin of TPA-treated hairless mice.
The Journal of dermatology, 2004Co-Authors: Hiroaki Sato, Yasunori Nakayama, Chizuru Yamashita, Hiroshi UnoAbstract:Tacalcitol (1,24(R)(OH)2D3, TV-02) inhibited the TPA-induced inflammatory cell infiltration (largely neutrophils) histopathologically and myeloperoxidase (MPO) activity dose-dependently. Tacalcitol inhibited the mRNA expression and protein production of TPA-induced macrophage inflammatory protein-2 (MIP-2) and KC, the functional analogue of human interleukin (IL)-8, in the skin. Immunohistochemical staining of the TPA-applied skin revealed that mast cells expressed MIP-2, whereas KC was observed in keratinocytes, fibroblasts and outer root sheath of hair follicles. Furthermore, Tacalcitol inhibited TPA-induced mast cell degranulation 24 hr after application without influence on the total number of mast cells. In this study, Tacalcitol was found to have an inhibitory effect on cutaneous inflammation such as inhibition of neutrophil infiltration, MIP-2 and KC production, and mast cell degranulation in TPA-treated hairless mice. These results suggest that Tacalcitol modulates cutaneous inflammation as well as keratinocyte proliferation and differentiation, and the inhibitory effect of Tacalcitol on cutaneous inflammation may contribute to clinical the effectiveness in the treatment of psoriasis.
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pharmacological profiles of high concentration 20 μg g Tacalcitol ointment effects on cutaneous inflammation epidermal proliferation and differentiation in mice
Journal of Dermatology, 2003Co-Authors: Hiroaki Sato, Yasuhiro Ogino, Hideko Takagi, Junko Hata, Satoshi Asano, Tomohiro Ohta, Keiji KomoriyaAbstract: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.
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Pharmacological Profiles of High‐Concentration (20 μg/g) Tacalcitol Ointment: Effects on Cutaneous Inflammation, Epidermal Proliferation, and Differentiation in Mice
The Journal of dermatology, 2003Co-Authors: Hiroaki Sato, Yasuhiro Ogino, Hideko Takagi, Junko Hata, Satoshi Asano, Tomohiro Ohta, Keiji KomoriyaAbstract: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.
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Regulation of RANTES and IL-8 production in normal human dermal fibroblasts by active vitamin D3 (Tacalcitol)
British journal of pharmacology, 1998Co-Authors: Masami Fukuoka, Hiroaki Sato, Yasuhiro Ogino, Tomohiro Ohta, Keiji KomoriyaAbstract:1 The production of chemokines, RANTES and IL-8 in cultured human dermal fibroblasts and the effects of Tacalcitol (1α,24(R)-dihydroxyvitamin D3) were studied using an enzyme-linked immunosorbent assay. 2 In the unstimulated condition, RANTES and IL-8 were at a trace level in the culture supernatant. On stimulation with TNF-α alone for 24 h, RANTES and IL-8 production were induced. Tacalcitol suppressed RANTES and IL-8 production dose-dependently at concentrations between 10−12m and 10−7m. 3 When the cells were treated with TNF-α and IFN-γ in combination, RANTES production was enhanced, but IL-8 production was not changed, compared to TNF-α-treated cells. Tacalcitol decreased IL-8 production dose-dependently as observed in the TNF-α-treated cells. On the other hand, RANTES production was enhanced by 10−11m and 10−10m of Tacalcitol, and dose-dependently suppressed by Tacalcitol concentrations higher than 10−9m. 4 Active vitamin D3 compounds, betamethasone valerate and cyclosporin A were compared with respect to their effects on chemokine production. Three active vitamin D3 compounds, Tacalcitol, 1α,25-dihydroxyvitamin D3 and MC903 (calcipotriol), inhibited the production of RANTES and IL-8, with very similar potencies. Betamethasone valerate also inhibited these chemokine productions, but with greater potency than active vitamin D3 compounds. Cyclosporin A significantly stimulated RANTES production at 10−6m and IL-8 production at 10−7m and 10−6m. 5 The results of this study suggest that active vitamin D3 compounds exert some beneficial effects in the treatment of inflammatory skin diseases via regulation of the production of chemokines by dermal fibroblasts. British Journal of Pharmacology (1998) 124, 1433–1438; doi:10.1038/sj.bjp.0701988
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Tacalcitol (1,24(OH)2D3, TV-02) inhibits phorbol ester-induced epidermal proliferation and cutaneous inflammation, and induces epidermal differentiation in mice.
Archives of dermatological research, 1996Co-Authors: Hiroaki Sato, Tomohiro Ohta, Hiroshi Uno, Izuki Sugimoto, Takashi Matsunaga, Masahiro Tsuchimoto, Mamoru KiyokiAbstract: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.
Hajime Iizuka - One of the best experts on this subject based on the ideXlab platform.
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Similarly potent action of 1,25-dihydroxyvitamin D3 and its analogues, Tacalcitol, calcipotriol, and maxacalcitol on normal human keratinocyte proliferation and differentiation
Journal of dermatological science, 2003Co-Authors: Hidetoshi Takahashi, Yoshio Hashimoto, Masaki Ibe, Motoshi Kinouchi, Akemi Ishida-yamamoto, Hajime IizukaAbstract:Abstract Background: The active vitamin D3 regulates proliferation and differentiation of epidermal keratinocytes. Recently topical vitamin D3, Tacalcitol, calcipotriol, and maxacalcitol are widely used for psoriasis. Objective: To examine the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on cultured normal keratinocytes (NHK) and compared its effect with those of various vitamin D3 analogues. Methods: Cell proliferation of NHK cells was analyzed by MTS, BrdU and 3 H-thymidine incorporation. The expression of involucrin, transglutaminase 1, keratin 5 and keratin 1 was investigated by western blot and PCR amplification and quantitative assay. Furthermore, we performed cornified cell envelope (CE) formation assay. Results: 1,25(OH)2D3, Tacalcitol, calcipotriol, and maxacalcitol decreased NHK cell proliferation in a concentration-dependent manner and the maximal effect was observed at 10 −7 M. There was no significant difference in the anti-proliferative effect among the active vitamin D3 analogues. The expression of involucrin and transglutaminase 1 were induced by 1,25(OH)2D3 and its analogues in mRNA and protein levels. CE formation was also induced by 1,25(OH)2D3 and its analogues. There was no significant difference in the potency among these chemicals. Keratin 5 and 1 expression was not altered by these active vitamin D3 analogues. Conclusions: The present study demonstrated that active vitamin D3 analogues, Tacalcitol, calcipotriol, and maxacalcitol, suppress keratinocyte proliferation and induce differentiation with similar potency.
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Topical Tacalcitol (1,24-(R)-dihydroxyvitamin D3) induces a transient increase in thymidine incorporation and calmodulin content in pig epidermis following tape stripping in vivo
Journal of dermatological science, 1995Co-Authors: Yoshio Hashimoto, Masato Tsutsui, Shinobu Matsuo, Susumu Iizuka, Hajime IizukaAbstract:Abstract Tape stripping induces transient increase in keratinocyte proliferation in vivo. The effects of Tacalcitol (l,24-(R)-dihydroxyvitamin D3) ointment on the cell kinetics of pig epidermis after the tape stripping were investigated. The Tacalcitol ointment (2 μg/g) was applied once to the back of pigs immediately after the tape stripping. The pig epidermal cell kinetics were analyzed at various times following the treatment. Tape stripping transiently increased thymidine incorporation of keratinocytes; the maximal effect was observed at 24 h. Tape stripping-induced increase in thymidine incorporation was markedly augmented by Tacalcitol treatment. At 24 h following the tape stripping DNA-flow cytometry revealed an accelerated transition from G 0 1 to S phase of cell cycle in Tacalcitol treated epidermis. There was no significant difference, however, in mitotic counts and G 2 M phase fractions between tape stripping-treated and tape stripping plus Tacalcitol ointment-treated epidermis. We also measured calmodulin content of pig epidermis following the treatments. Although tape stripping slightly increased calmodulin content of pig epidermis, this was statistically not significant. Tape stripping plus Tacalcitol ointment treatment resulted in a significant increase in calmodulin content at 24 h following the treatment. There was no significant difference in calmodulin content between tape stripping treated- and tape stripping plus Tacalcitol-treated epidermis.
Tomohiro Ohta - One of the best experts on this subject based on the ideXlab platform.
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pharmacological profiles of high concentration 20 μg g Tacalcitol ointment effects on cutaneous inflammation epidermal proliferation and differentiation in mice
Journal of Dermatology, 2003Co-Authors: Hiroaki Sato, Yasuhiro Ogino, Hideko Takagi, Junko Hata, Satoshi Asano, Tomohiro Ohta, Keiji KomoriyaAbstract: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.
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Pharmacological Profiles of High‐Concentration (20 μg/g) Tacalcitol Ointment: Effects on Cutaneous Inflammation, Epidermal Proliferation, and Differentiation in Mice
The Journal of dermatology, 2003Co-Authors: Hiroaki Sato, Yasuhiro Ogino, Hideko Takagi, Junko Hata, Satoshi Asano, Tomohiro Ohta, Keiji KomoriyaAbstract: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.
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Tacalcitol, an active vitamin D3, induces nerve growth factor production in human epidermal keratinocytes.
Skin pharmacology and applied skin physiology, 2001Co-Authors: Masami Fukuoka, Tomohiro Ohta, Mamoru Kiyoki, Katsutoshi Sakurai, Ichiro KatayamaAbstract: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 [1α,24(R)-dihydroxyv
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Regulation of RANTES and IL-8 production in normal human dermal fibroblasts by active vitamin D3 (Tacalcitol)
British journal of pharmacology, 1998Co-Authors: Masami Fukuoka, Hiroaki Sato, Yasuhiro Ogino, Tomohiro Ohta, Keiji KomoriyaAbstract:1 The production of chemokines, RANTES and IL-8 in cultured human dermal fibroblasts and the effects of Tacalcitol (1α,24(R)-dihydroxyvitamin D3) were studied using an enzyme-linked immunosorbent assay. 2 In the unstimulated condition, RANTES and IL-8 were at a trace level in the culture supernatant. On stimulation with TNF-α alone for 24 h, RANTES and IL-8 production were induced. Tacalcitol suppressed RANTES and IL-8 production dose-dependently at concentrations between 10−12m and 10−7m. 3 When the cells were treated with TNF-α and IFN-γ in combination, RANTES production was enhanced, but IL-8 production was not changed, compared to TNF-α-treated cells. Tacalcitol decreased IL-8 production dose-dependently as observed in the TNF-α-treated cells. On the other hand, RANTES production was enhanced by 10−11m and 10−10m of Tacalcitol, and dose-dependently suppressed by Tacalcitol concentrations higher than 10−9m. 4 Active vitamin D3 compounds, betamethasone valerate and cyclosporin A were compared with respect to their effects on chemokine production. Three active vitamin D3 compounds, Tacalcitol, 1α,25-dihydroxyvitamin D3 and MC903 (calcipotriol), inhibited the production of RANTES and IL-8, with very similar potencies. Betamethasone valerate also inhibited these chemokine productions, but with greater potency than active vitamin D3 compounds. Cyclosporin A significantly stimulated RANTES production at 10−6m and IL-8 production at 10−7m and 10−6m. 5 The results of this study suggest that active vitamin D3 compounds exert some beneficial effects in the treatment of inflammatory skin diseases via regulation of the production of chemokines by dermal fibroblasts. British Journal of Pharmacology (1998) 124, 1433–1438; doi:10.1038/sj.bjp.0701988
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Tacalcitol (1,24(OH)2D3, TV-02) inhibits phorbol ester-induced epidermal proliferation and cutaneous inflammation, and induces epidermal differentiation in mice.
Archives of dermatological research, 1996Co-Authors: Hiroaki Sato, Tomohiro Ohta, Hiroshi Uno, Izuki Sugimoto, Takashi Matsunaga, Masahiro Tsuchimoto, Mamoru KiyokiAbstract: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.
