目的观察CC趋化因子配体20(CCL20)在银屑病皮损中的表达及作用。方法采用免疫荧光观察银屑病患者及咪喹莫特诱导银屑病样小鼠皮损中CCL20的表达。采用胶带剥脱诱导小鼠银屑病模型,用银屑病皮损面积和疾病严重程度(psoriasis area and se...目的观察CC趋化因子配体20(CCL20)在银屑病皮损中的表达及作用。方法采用免疫荧光观察银屑病患者及咪喹莫特诱导银屑病样小鼠皮损中CCL20的表达。采用胶带剥脱诱导小鼠银屑病模型,用银屑病皮损面积和疾病严重程度(psoriasis area and severity index,PASI)评分标准,观察CCL20蛋白注射后银屑病样小鼠皮损的变化;显微镜下观察皮损组织形态学变化,测量表皮层垂直厚度。采用咪喹莫特诱导小鼠银屑病模型,用PASI评分标准,观察CCL20单克隆抗体注射对银屑病样小鼠皮损的影响,显微镜下观察皮损组织形态学变化,测量表皮层垂直厚度;免疫组化观察表皮增殖的变化;real-time PCR检测小鼠皮肤组织样本中CCL20的表达。结果银屑病患者及咪喹莫特诱导银屑病样小鼠皮损中CCL20的表达增加;CCL20蛋白复合胶带剥脱组(CCL20组)小鼠银屑病样皮损程度较重,红斑、鳞屑、浸润以及表皮增厚程度高于单纯胶带剥脱模型组;CCL20单克隆抗体组(anti-CCL20组)小鼠银屑病样皮损程度较轻,红斑、鳞屑、浸润、表皮增厚以及表皮细胞增殖程度轻于咪喹莫特模型组,皮肤组织CCL20的表达明显低于模型组。结论 CCL20在银屑病皮损中呈高表达,CCL20蛋白可加重胶带剥脱诱导小鼠银屑病样皮损,CCL20单克隆抗体注射对IMQ诱导的小鼠银屑病样皮损有一定的治疗作用。展开更多
Objective To assess the in vivo cutaneous bioavailability of iodiconazole in a topical formulation. Methods Iodiconazole cream was topically administrated to the ventral forearms of 10 healthy volunteers for 1 hour, a...Objective To assess the in vivo cutaneous bioavailability of iodiconazole in a topical formulation. Methods Iodiconazole cream was topically administrated to the ventral forearms of 10 healthy volunteers for 1 hour, and the excess formulation was removed. The stratum corneum (SC) at the application sites was tape-stripped immediately or at different time points, quantified gravimetrically, and extracted for analysis. Together with concomitant transepidermal water loss (TEWL) measurement, SC drug concentration-depth profiles were reproducibly determined and fitted mathematically to obtain the SC-vehicle partition coefficient (K) and a first-order rate constant (D/L2) related to iodiconazole diffusivity. The main pharmacokinetic parameters were calculated by Drug and Statistics software. With these parameters, the uptake of iodiconazole of time into SC was assessed. The variation of iodiconazole concentrations in stratum corneum post-removal of the formulation was also investigated. Results The mean values of K and D/L2 of 10 healthy volunteers were (0.13 ± 0.07) and (0.15 ± 0.08)/hour, respectively. The classic lag-time for diffusion (Tlag) across the SC varied from 0.52 hours to 2.28 hours. The mean value of time to reach steady-state transport (Tss) was (3.74 ± 1.69) hours. The mean values of the elimination half-life (t1/2) and the elimination rate constant (Kel) of 10 healthy volunteers were (8.47 ± 5.36) hours and (0.11 ± 0.05)/hour, respectively. Conclusions After topical application, iodiconaole penetrated into the SC rapidly and maintained a high concentration at the target site. The results of this study can provide reliable evidences for the clinical medication and the design of following phaseⅡstudy for iodiconazole.展开更多
文摘目的观察CC趋化因子配体20(CCL20)在银屑病皮损中的表达及作用。方法采用免疫荧光观察银屑病患者及咪喹莫特诱导银屑病样小鼠皮损中CCL20的表达。采用胶带剥脱诱导小鼠银屑病模型,用银屑病皮损面积和疾病严重程度(psoriasis area and severity index,PASI)评分标准,观察CCL20蛋白注射后银屑病样小鼠皮损的变化;显微镜下观察皮损组织形态学变化,测量表皮层垂直厚度。采用咪喹莫特诱导小鼠银屑病模型,用PASI评分标准,观察CCL20单克隆抗体注射对银屑病样小鼠皮损的影响,显微镜下观察皮损组织形态学变化,测量表皮层垂直厚度;免疫组化观察表皮增殖的变化;real-time PCR检测小鼠皮肤组织样本中CCL20的表达。结果银屑病患者及咪喹莫特诱导银屑病样小鼠皮损中CCL20的表达增加;CCL20蛋白复合胶带剥脱组(CCL20组)小鼠银屑病样皮损程度较重,红斑、鳞屑、浸润以及表皮增厚程度高于单纯胶带剥脱模型组;CCL20单克隆抗体组(anti-CCL20组)小鼠银屑病样皮损程度较轻,红斑、鳞屑、浸润、表皮增厚以及表皮细胞增殖程度轻于咪喹莫特模型组,皮肤组织CCL20的表达明显低于模型组。结论 CCL20在银屑病皮损中呈高表达,CCL20蛋白可加重胶带剥脱诱导小鼠银屑病样皮损,CCL20单克隆抗体注射对IMQ诱导的小鼠银屑病样皮损有一定的治疗作用。
文摘Objective To assess the in vivo cutaneous bioavailability of iodiconazole in a topical formulation. Methods Iodiconazole cream was topically administrated to the ventral forearms of 10 healthy volunteers for 1 hour, and the excess formulation was removed. The stratum corneum (SC) at the application sites was tape-stripped immediately or at different time points, quantified gravimetrically, and extracted for analysis. Together with concomitant transepidermal water loss (TEWL) measurement, SC drug concentration-depth profiles were reproducibly determined and fitted mathematically to obtain the SC-vehicle partition coefficient (K) and a first-order rate constant (D/L2) related to iodiconazole diffusivity. The main pharmacokinetic parameters were calculated by Drug and Statistics software. With these parameters, the uptake of iodiconazole of time into SC was assessed. The variation of iodiconazole concentrations in stratum corneum post-removal of the formulation was also investigated. Results The mean values of K and D/L2 of 10 healthy volunteers were (0.13 ± 0.07) and (0.15 ± 0.08)/hour, respectively. The classic lag-time for diffusion (Tlag) across the SC varied from 0.52 hours to 2.28 hours. The mean value of time to reach steady-state transport (Tss) was (3.74 ± 1.69) hours. The mean values of the elimination half-life (t1/2) and the elimination rate constant (Kel) of 10 healthy volunteers were (8.47 ± 5.36) hours and (0.11 ± 0.05)/hour, respectively. Conclusions After topical application, iodiconaole penetrated into the SC rapidly and maintained a high concentration at the target site. The results of this study can provide reliable evidences for the clinical medication and the design of following phaseⅡstudy for iodiconazole.
