Acne Scars

Zhonghua Yi Xue Za Zhi. 2009 Apr 28; 89(16): 1088-92Diao JS, Zhang X, Ren J, Zeng HF, Liu B, Ma FC, Wang YM, Yang XT, Guo SZ, Xia WOBJECTIVE: To investigate the effects of Notch signaling on scars in a rabbit ear model of hypertrophic scarring. METHODS: The hypertrophic scar of rabbits' ears was reproduced. The left rabbit's ear wounds as the N-[N-(3,5-difluorophenacetyl-L-alanyl)]-(S)-phenylglycine t-butyl ester (DAPT) treated group were treated intradermally with the gamma-secretase inhibitor DAPT to inhibit the activation of Notch at 1, 3, 7 and 14 day time points. The right ears as the control group were treated with normal saline at the same time points. Experimental and control wounds were harvested on days 14, 21, 28 and 35 post wounding, and then examined histologically to quantify hypertrophic index and fibroblasts. The expression of epidermal differentiation markers-keratin 14 (K14), keratin 19 (K19), Involucrin and Notch downstream molecules-P21, P63 were examined and analyzed with immunohistochemistry staining. RESULTS: Both hypertrophic index (1.93 +/- 0.32, 1.82 +/- 0.36, 1.79 +/- 0.25) and number of fibroblasts [(4.08 +/- 0.88), (3.30 +/- 0.53), (3.19 +/- 0.73) x 10(3)/mm(2)] in the DAPT treated group were significantly reduced on days 21, 28 and 35, compared with the control group [2.56 +/- 0.29, 2.61 +/- 0.30, 2.58 +/- 0.39, and (5.45 +/- 0.99), (4.80 +/- 1.13), (4.43 +/- 1.17) x 10(3)/mm(2), all P < 0.01)]. The K19, K14 and P63 increased their expression in the DAPT treated group (28.6% +/- 5.7%, 53.1% +/- 4.5%, 57.0% +/- 5.8%) relative to the control group (10.1% +/- 2.8%, 30.8% +/- 4.9%, 16.5% +/- 2.2%, all P < 0.01) on day 14 post wounding, while the Involucrin and P21 decreased their expression in the DAPT treated group (12.3% +/- 1.9%, 11.0% +/- 1.7%) relative to the control group (29.3% +/- 4.6%, 44.3% +/- 3.5%, both P < 0.01). CONCLUSION: Inactivation of Notch signaling will inhibit scar epidermis to over-differentiation, and thereby inhibit proliferation of hypertrophic scars in the rabbit ears.

PLoS One. 2009; 4(7): e6227Desclaux M, Teigell M, Amar L, Vogel R, Gimenez Y Ribotta M, Privat A, Mallet JBACKGROUND: The lack of axonal regeneration in the central nervous system is attributed among other factors to the formation of a glial scar. This cellular structure is mainly composed of reactive astrocytes that overexpress two intermediate filament proteins, the glial fibrillary acidic protein (GFAP) and vimentin. Indeed, in vitro, astrocytes lacking GFAP or both GFAP and vimentin were shown to be the substrate for increased neuronal plasticity. Moreover, double knockout mice lacking both GFAP and vimentin presented lower levels of glial reactivity in vivo, significant axonal regrowth and improved functional recovery in comparison with wild-type mice after spinal cord hemisection. From these results, our objective was to develop a novel therapeutic strategy for axonal regeneration, based on the targeted suppression of astroglial reactivity and scarring by lentiviral-mediated RNA-interference (RNAi). METHODS AND FINDINGS: In this study, we constructed two lentiviral vectors, Lv-shGFAP and Lv-shVIM, which allow efficient and stable RNAi-mediated silencing of endogenous GFAP or vimentin in vitro. In cultured cortical and spinal reactive astrocytes, the use of these vectors resulted in a specific, stable and highly significant decrease in the corresponding protein levels. In a second model -- scratched primary cultured astrocytes -- Lv-shGFAP, alone or associated with Lv-shVIM, decreased astrocytic reactivity and glial scarring. Finally, in a heterotopic coculture model, cortical neurons displayed higher survival rates and increased neurite growth when cultured with astrocytes in which GFAP and vimentin had been invalidated by lentiviral-mediated RNAi. CONCLUSIONS: Lentiviral-mediated knockdown of GFAP and vimentin in astrocytes show that GFAP is a key target for modulating reactive gliosis and monitoring neuron/glia interactions. Thus, manipulation of reactive astrocytes with the Lv-shGFAP vector constitutes a promising therapeutic strategy for increasing glial permissiveness and permitting axonal regeneration after central nervous system lesions.

Zhonghua Yi Xue Za Zhi. 2009 Apr 28; 89(16): 1093-7Tao L, Liu JY, Li SR, Dai X, Li ZOBJECTIVE: To validate whether STAT1 paticipated in the process of CTGF-induced proliferation and differentiation of human hypertrophic scar fibroblast (hHSF) on account of past research. METHODS: To cultivate hHSF with 6 patients' hypertrophic scar specimens together. Electrophoretic mobility shift assay (EMSA) was used to verify binding ability between DNA and STAT1 with the stimulus of different concertration CTGF (0, 5, 7.5, 10, 15 ng/ml) at 45th min and the stimulus of 10 ng/ml CTGF at different phase point (0, 10, 20, 30, 45, 60, 90, and 120 min). We divided cells into CTGF group, STAT1 ASODN group. STAT1 ASODN + CTGF group. control group. And MTT was used to detect the proliferation of hHSF on days1, 2 and 3, and RT-PCR to detect alpha-smouth muscle actin mRNA to follow the differentiation. RESULTS: EMSA showed that the binding ability between STAT1 and DNA depended on the concentration of CTGF and peaked with the stimulation of 10ng/ml CTGF. And at the same time, it peaked at 45 - 60 min with 10 ng/ml CTGF. MTT showed that cell proliferation of CTGF group was much higher than that of control group (all P < 0.05). And those of STAT1 ASODN group and STAT1 ASODN + CTGF group were much lower than those of control group and CTGF group (all P < 0.05). RT-PCR showed that differentiation activation from fibroblast to myofibroblast of CTGF group, STAT1 ASODN group, STAT1 ASODN + CTGF group and control group were 0.78 +/- 0.08, 0.38 +/- 0.09, 0.76 +/- 0.10, and 0.40 +/- 0.12, respectively. Differentiation activation of STAT1 ASODN group and control group were much lower than those of CTGF group and STAT1 ASODN + CTGF group (all P < 0.05). CONCLUSION: STAT1 ASODN is important in the process of proliferation of hHSF and it blocks the stimulation of CTGF on hHSF proliferation. The above result revealed that STAT1 participates in the process of hHSF proliferation induced by connective tissue growth factor.

Zhonghua Yi Xue Za Zhi. 2009 Apr 28; 89(16): 1093-7Tao L, Liu JY, Li SR, Dai X, Li ZOBJECTIVE: To validate whether STAT1 paticipated in the process of CTGF-induced proliferation and differentiation of human hypertrophic scar fibroblast (hHSF) on account of past research. METHODS: To cultivate hHSF with 6 patients' hypertrophic scar specimens together. Electrophoretic mobility shift assay (EMSA) was used to verify binding ability between DNA and STAT1 with the stimulus of different concertration CTGF (0, 5, 7.5, 10, 15 ng/ml) at 45th min and the stimulus of 10 ng/ml CTGF at different phase point (0, 10, 20, 30, 45, 60, 90, and 120 min). We divided cells into CTGF group, STAT1 ASODN group. STAT1 ASODN + CTGF group. control group. And MTT was used to detect the proliferation of hHSF on days1, 2 and 3, and RT-PCR to detect alpha-smouth muscle actin mRNA to follow the differentiation. RESULTS: EMSA showed that the binding ability between STAT1 and DNA depended on the concentration of CTGF and peaked with the stimulation of 10ng/ml CTGF. And at the same time, it peaked at 45 - 60 min with 10 ng/ml CTGF. MTT showed that cell proliferation of CTGF group was much higher than that of control group (all P < 0.05). And those of STAT1 ASODN group and STAT1 ASODN + CTGF group were much lower than those of control group and CTGF group (all P < 0.05). RT-PCR showed that differentiation activation from fibroblast to myofibroblast of CTGF group, STAT1 ASODN group, STAT1 ASODN + CTGF group and control group were 0.78 +/- 0.08, 0.38 +/- 0.09, 0.76 +/- 0.10, and 0.40 +/- 0.12, respectively. Differentiation activation of STAT1 ASODN group and control group were much lower than those of CTGF group and STAT1 ASODN + CTGF group (all P < 0.05). CONCLUSION: STAT1 ASODN is important in the process of proliferation of hHSF and it blocks the stimulation of CTGF on hHSF proliferation. The above result revealed that STAT1 participates in the process of hHSF proliferation induced by connective tissue growth factor.

Biomed Tech (Berl). 2009 Jul 14; Venhaus M, Behn C, Freitag L, Zimmermann KAbstract This article investigates the mechanics of balloon dilatation in the treatment of bronchotracheal stenosis. The "scar stricture"-type stenosis examined in this paper is typically dilated manually, using a dilatation balloon. If indicated, this is followed by stent implantation. The selection of the stent with proper characteristics is performed empirically, based on personal experience and preference. In order to optimize the therapeutic outcome, however, it is necessary to match the stent with the stress-strain properties of the stenosis, which are not determined during manual balloon dilatation. The objective is to utilize models to experimentally and theoretically establish the correlation between the pressure/volume curve measured during the dilatation and the stress-strain properties of the stenosis, taking into account that during dilatation of scar strictures the balloon is only partially compressed, as it extends beyond both ends of the stenosis. Experiments are carried out using stenosis models with various extensibilities and lengths. As expected, more hardened stenosis resulted in steeper pressure/volume curves during the dilatation. On the other hand, the comparison between stenosis of equal extensibilities, but different length, showed an initially unexpected larger distension of the shorter stenosis, at equal pressure increases. This is caused by the fact that the margins of the stenosis are allowed more time to distend, compared to the central areas of the stenosis. The term "effect of margin expansion" was introduced to describe this behavior. The modeling of the dilatation process is based on the equilibrium conditions of cut-free balloon portions. The balloon/stenosis system is divided into three areas with different characteristics: (1) the proximal and distal area of the balloon outside the stenosis; (2) the area of contact between the balloon and the stenosis; and (3) the transition area between (1) and (2). Numerical simulations of the balloon dilatation confirm the conclusions from the experimental results and the theoretical considerations regarding the correlation between the pressure/volume curve of the dilatation and the stress-strain properties of the stenosis.