Efficacy and safety of two prolonged therapeutic regimens in patients with plaque psoriasis after treatment with tazarotene/betamethasone dipropionate cream: a multicenter clinical observation / 中华皮肤科杂志

Objective:To explore the prolonged therapeutic regimen for patients with plaque psoriasis, who showed a positive response to 4-week treatment with tazarotene/betamethasone dipropionate cream, but were not completely cured.Methods:A multicenter, randomized, open-labelled, parallel-controlled clinical study was conducted. A total of 232 patients with plaque psoriasis were collected, who showed a positive response to previous 4-week treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream, but were not completely cured with the psoriasis area and severity index[PASI] improvement rate being 50%-90%. At week 5, they were randomly and equally divided into 2 groups: test group receiving treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream once a day, and control group receiving a sequential regimen of 0.05% tazarotene gel on weekdays once a day followed by 0.05%/0.05% tazarotene/betamethasone dipropionate cream on weekends once a day. After 2-and 4-week prolonged treatment, the efficacy and safety of the 2 therapeutic regimens were evaluated and compared. Measurement data were compared between 2 groups by using covariance analysis or t test, and enumeration data were compared by using chi-square test. Results:From the 5th to the 8th week, 200 out of the 232 patients completed the treatment. Data collected from 110 patients in the test group and 112 in the control group were enrolled into the full analysis set, and those from both 113 patients in the test group and control group were enrolled into safety analysis set. After consecutive 6-and 8-week treatment, the decline rates of the PASI score were 73.05% ± 16.69% and 78.46% ± 15.40% respectively in the test group, which were significantly higher than those in the control group (66.73% ± 21.77%, 67.02% ± 34.19%, respectively, both P < 0.05) . After 6-week treatment, the proportion of subjects who achieved PASI90 was significantly higher in the test group (14 cases, 12.7%) than in the control group (5 cases, 4.5%, χ2=4.842, P=0.028) ; After 8-week treatment, the proportions of subjects who achieved PASI75 and PASI90 (61.8%, 23.6%, respectively) were significantly higher in the test group than in the control group (48.2%, 12.5%, respectively, both P < 0.05) . During the consecutive 8-week treatment, there was no significant difference in the incidence rate of adverse reactions between the test group (15.0%) and control group (23.9%, χ2=2.822, P=0.093) . Conclusion:For patients who showed a positive response to 4-week treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream, but were not completely cured, the continuous use of 0.05%/0.05% tazarotene/betamethasone dipropionate cream for 4 weeks is a superior therapeutic regimen compared with the sequential regimen of 0.05% tazarotene gel followed by 0.05%/0.05% tazarotene/betamethasone dipropionate cream.

In Vivo Evaluation Of Tazarotene Solid Lipid Nanoparticles Gel For Topical Delivery

The purpose of this research work was to develop and optimize the Solid Lipid Nanoparticles (SLNs) of Tazarotene for the effective topical delivery in the treatment of psoriasis. Tazarotene loaded SLNs were prepared by hot homogenization followed by the ultrasonication using Taguchi’s design and based on the results further investigation was made using central composite design. The lipid Dynasan-116, surfactant poloxomer-188 and co surfactant egg lecithin resulted in better percent drug loading and evaluated for particle size, zeta potential, TEM, drug entrapment efficiency, in vitro drug release and stability. All parameters were found to be in an acceptable range. In vitro drug release of optimized SLN formulation (F1) was found to be 98.12 ± 1.52%, whereas pure drug release was 42.12 after 60 min. The optimized formulation was incorporated into the gel. The release rate (flux) of tazarotene across the membrane and excised skin differs significantly. The accumulative amount of Tazarotene in skin from SLN based gel formulation and marketed gel were 41.12 ± 0.12 mg and 30.02 ± 0.04 mg respectively. This result supported our hypothesis made in skin permeation studies on rat skin. From histopathological studies the microscopic observations indicate that the optimized SLN formulation, SLN based gel formulation and marketed gel has no significant effect on the microscopic structure of the skin. The skin-irritation studies indicated that SLN based gel containing Tazarotene did not show any sign of skin irritation as compared to moderate erythema shown by marketed gel formulation (Tazret® gel) after 72 h of application. Thus, SLN based gel formulation demonstrated advantage over marketed formulation in improving the skin tolerability of Tazarotene indicating their potential in improving patient acceptance and topical delivery of Tazarotene.

Ictiosis ligada al x tratada con tazarotene tópico / X-linked ichthyosis treated with tazarotene topic

La Ictiosis ligada al cromosoma X (ILX), es una genodermatosis poco frecuente que afecta a varones, se manifiesta a partir del período neonatal y se caracteriza por: xerodermia, hiperqueratosis, descamación y en algunos casos, manifestaciones extracutáneas. La delección total o parcial de la enzima sulfatasa esteroidea, es la causa de las manifestaciones clínicas. Presentamos el caso clínico, de un paciente con manifestaciones clínicas y hallazgos en la anatomía patológica, compatibles con esta entidad tratado con tazarotene (gel).

X-linked ichthyosis (XLI) is a rare genodermatosis that affects men and manifests from the neonatal period and is characterized by xeroderma, hyperkeratosis, desquamation and in some cases, extracutaneous manifestations. The disease is of chronic evolution and undergoes partial improvement in the summer season. The total or partial deletion of the steroid sulphatase enzyme is the cause of the clinical manifestations. We present the case of a patient with clinical manifestations and findings in the pathological anatomy compatible with this entity, as well as ITS treatment with topical tazarotene 0.1% (gel) Weekly controls were performed and clinical benefit of lesion-free skin was observed up to 6 weeks after treatment discontinuation, followed by the progressive appearance of brownish scales that became thick and adherent with the passage of time.

Molecular evolution and expression profile of the chemerine encoding gene RARRES2 in baboon and chimpanzee

BACKGROUND: Chemerin, encoded by the retinoic acid receptor responder 2 (RARRES2) gene is an adipocytesecreted protein with autocrine/paracrine functions in adipose tissue, metabolism and inflammation with a recently described function in vascular tone regulation, liver, steatosis, etc. This molecule is believed to represent a critical endocrine signal linking obesity to diabetes. There are no data available regarding evolution of RARRES2 in non-human primates and great apes. Expression profile and orthology in RARRES2 genes are unknown aspects in the biology of this multigene family in primates. Thus; we attempt to describe expression profile and phylogenetic relationship as complementary knowledge in the function of this gene in primates. To do that, we performed A RT-PCR from different tissues obtained during necropsies. Also we tested the hypotheses of positive evolution, purifying selection, and neutrality. And finally a phylogenetic analysis was made between primates RARRES2 protein. RESULTS: RARRES2 transcripts were present in liver, lung, adipose tissue, ovary, pancreas, heart, hypothalamus and pituitary tissues. Expression in kidney and leukocytes were not detectable in either species. It was determined that the studied genes are orthologous. CONCLUSIONS: RARRES2 evolution fits the hypothesis of purifying selection. Expression profiles of the RARRES2 gene are similar in baboons and chimpanzees and are also phylogenetically related.

Efficacy of 308-nm excimer laser combined with tazarotene gel for the treatment of plaque psoriasis / 中华皮肤科杂志

Objective To investigate the clinical efficacy and safety of 308-nm excimer laser combined with tazarotene gel for the treatment of plaque psoriasis.Methods Seventy-two patients with plaque psoriasis were randomly and equally divided into three groups according to a random number table:tazarotene group topically applying tazarotene gel once per night,308-nm excimer laser group treated with 308-nm excimer laser,combination group treated with both tazarotene gel and 308-nm excimer laser.Clinical efficacy was evaluated according to psoriasis area and severity index (PASI) score and response rate,and safety according to adverse reactions at week 2,4 and 8 after starting treatment.Results PASI score was significantly lower in the combination group at week 4 and 8 (4.75 ± 0.44 and 2.35 ± 0.37 respectively) than in the 308-nm excimer laser group (6.75 ± 0.57 and 4.67 ± 0.36 respectively,both P ＜ 0.05) and tazarotene group (8.75 ± 0.48 and 6.48 ± 0.45 respectively,both P ＜ 0.05),and significantly lower in the combination group at week 8 than at week 2 and 4 (both P ＜ 0.05).A significant increase was observed in the response rate at week 2,4,and 8 in the combination group (29.1％ (7/24),66.7％ (16/24) and 87.5％ (21/24) respectively) compared with the tazarotene group (12.5％ (3/24),41.7％ (10/24) and 62.5％ (15/24) respectively,all P＜ 0.05) and 308-nm excimer laser group (20.8％ (5/24),50.0％ (12/24) and 75.0％ (18/24) respectively,all P＜ 0.05).No systemic adverse reactions were observed in any of the 3 groups during the study,and there was no significant difference in the incidence of local adverse reactions between the combination group,tazarotene group and 308-nm excimer laser group (16.7％ (4/24) vs.12.5％ (3/24) vs.12.5％ (3/24),P ＞ 0.05).Conclusion The efficacy of 308-nm excimer laser combined with tazarotene gel is superior to that of tazarotene gel or 308-nm excimer laser alone in the treatment of plaque psoriasis.

Effects of interleukin-22 on the expression of tazarotene-induced gene 3 in HaCaT cells / 中华皮肤科杂志

Objective To evaluate the effects of interleukin-22(IL-22)on the expression of tazarotene-induced gene 3(TIG3)in HaCaT cells. Methods Cultured HaCaT cells were randomly divided into several groups to be treated with different concentrations (12.5, 25, 50, 100 μg/L)of IL-22 alone, or the combination of 50 μg/L IL-22 with the MAPK-ERK1/2 inhibitor PD98059 or the JAK/STAT inhibitor AG490 for 24 hours. Those HaCaT cells treated with phosphate buffered saline served as the control group. Subsequently, total proteins and mRNAs were extracted from the HaCaT cells. An immunofluorescence assay, Western blot and enzyme-linked immunosorbent assay (ELISA) were performed to determine the protein expression level of TIG3, and real-time fluorescence-based quantitative PCR to quantify the mRNA expression of TIG3 in HaCaT cells. Results The immunofluorescence assay showed that TIG3 protein was mainly expressed in the cytoplasm of HaCaT cells. As Western blot revealed, the protein expression level of TIG3 was 0.743 ± 0.035, 0.678 ± 0.040, 0.582 ± 0.041 and 0.328 ± 0.032 in HaCaT cells treated with IL-22 of 12.5, 25, 50 and 100μg/L, respectively, significantly lower than that in the control group (0.839 ± 0.045, all P<0.05). ELISA also showed a decrease in the protein expression of TIG3 in IL-22-treated HaCaT cells, which was consistent with Western blot results. Further more, the mRNA expression level (2-△△Ct)of TIG3 was significantly weaker in HaCaT cells treated with IL-22 of 12.5, 25, 50 and 100μg/L than in the control group (0.838 ± 0.036, 0.686 ± 0.061, 0.565 ± 0.047 and 0.457 ± 0.033 vs. 1.000, all P< 0.05). The decrease in TIG3 mRNA and protein expressions was significantly attenuated in HaCaT cells treated with the combination of 50 μg/L IL-22 with PD98059 or AG490 compared with those treated with 50 μg/L IL-22 alone. Conclusion IL-22 can dose-dependently inhibit the expression of TIG3 in HaCaT cells, likely through the MAPK-ERK1/2 and JAK2/STAT3 signaling pathways.

Therapeutic Effects of Tazarotene on Psoriasis and Its Potential Action Mechanism in Inflammatory Angiogenesis / 대한피부과학회지

BACKGROUND: Psoriasis is characterized by chronic recurrent erythematous skin plaques that exhibit epidermal hyperplasia, inflammatory cell accumulation and abnormalities of the papillary dermal vasculature. Psoriatic skin lesions show enlargement and increased tortuosity of cutaneous microvessels without formation of new vessel sprouts, that is, inflammatory angiogenesis. Placental growth factor (PlGF) and Tie-2 were reported to be up-regulated during inflammatory angiogenesis. Tazarotene is the first receptor-selective retinoid and its effects include normalizing keratinocyte differentiation, reducing keratinocyte proliferation and reducing inflammation. OBJECTIVE: Our study evaluated the clinical efficacy of topical tazarotene treatment and clarified histological changes and possible action mechanisms of this agent in respect of inflammatory angiogenesis. METHODS: We selected patients with symmetric psoriatic lesions and applied 0.1% tazarotene gel (Tazorac(R)) versus calcitriol 3 microgram/g gel (Silkis(R)) twice a day for 12 weeks with a right-left comparison. We grouped the patients with treatment modalities. Clinical efficacy, which was measured by the overall lesional assessment (OLA) scores, was assessed at each visit in 2 week' intervals until treatment closed. Skin biopsies were performed before the treatment started and again at 4 weeks and 12 weeks after treatment. Immunohistochemistry of PlGF, Tie-2 and factor-VIII was performed to elucidate the anti-angiogenetic effect of tazarotene. RESULTS: At the completion of 12 weeks of treatment, the OLA score of tazarotene-treated lesions was more reduced than that of calcitriol-treated lesions combined with phototherapy, it was more effective. Several histologic features such as epidermal hyperplasia, inflammatory cell infiltration and vessel dilation/tortousity were improved with decreased PlGF and Tie-2 expressions. CONCLUSION: These results indicate that tazarotene is an effective topical agent for psoriasis by blocking inflammatory angiogenesis.

Hypermethylation of TIG1 in Head and Neck Cancer / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Decreased expression and growth suppression of Tazarotene-Induced Gene 1 (TIG1) were reported in prostate cancer. In this study, we examined the possibility of TIG1 transcriptional silencing by hypermethylation in head and neck cancer. SUBJECTS AND METHOD: We extracted DNA and total RNA from five head and neck cell lines (O11, O12, O19, O22 and O28), and three prostate cell lines (PC3, LNCap and DU145). We checked the methylation status of TIG1 by methylation-specific PCR (MSP) and RT-PCR. We also examined primary cancer tissues of 32 head and neck cancer, 31 prostate cancer and 10 normal samples. RESULTS: We found that all of five head and neck (100%) cell lines and two of three prostate (66.7%) cell lines were methylated. RT-PCR analysis confirmed the absence of TIG1 expression in six cell lines with methylation. We checked primary cancer by MSP and found TIG1 methylation in 16 of 32 (50%) head and neck cancers, and 17 of 31 (54.8%) prostate cancers. Normal head and neck and prostate tissues were free of methylation. CONCLUSION: Our results support the notion that methylation might be an important mechanism of TIG1 inactivation and a target event in head and neck cancer.

Clinical Application and Efficacy of Tazarotene Cream for Acne Vulgaris / 中国药房

OBJECTIVE:To provide optimal therapeutic scheme for patients with acne vulgaris. METHODS: By a single-blind randomized controlled method,a total of 122 patients with acne vulgaris were assigned to one of the following 3 groups: tazarotene cream group(n=42),Water chlorine tincture group(n=38) and combined treatment group(n=42). The curative efficacy was observed after treatment for 8 consecutive weeks. RESULTS: The number of skin lesions in all the 3 groups reduced as the course of treatment increased,and there were significant differences across the 3 groups after 8-week treatment as compared with before treatment (P0.05). CONCLUSION: Tazarotene cream is effective for non-inflammatory acne. The superior efficacy of water chlorine tincture as compared with tazarotene for patients with impetigo might be related to the antibacterial action of chloramphenicol. Tazarotene cream combined with local application of 0.5% water chlorine tincture is effective for inflammatory acne.

Regulation of tazarotene on HB-EGF in hyperproliferative epidermis of psoriasis / 西安交通大学学报(医学版)

Objective To investigate the mechanism of tazarotene in active psoriasis vulgaris. Methods HB-EGF mRNA in active psoriatic lesions before and 10 days after the treatment with tazarotene was detected by hybridization in situ. Results There was nearly no expression of HB-EGF mRNA in psoriatic lesions (9.1%); after the treatment with tazarotene, there was expression of HB-EGF not only in basal layer (95.5%), but also focal expression in suprabasal layers of epidermis (77.3%). Conclusion Tazarotene can inhibit proliferation and induce apoptosis of keratinocytes though upregulating expression of HB-EGF in psoriatic epidermis.