Efficacy of dermal scaffold for promoting repair of acute full-thickness skin defects in pigs / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the efficacy of Lando dermal scaffold for promoting repair of acute full-thickness skin defects in pigs and explore the possible mechanism.</p><p><b>METHODS</b>Three 5 cm×5 cm full-thickness skin defects were created on the left dorsal skin (control group) and another 3 on the right dorsal skin (treatment group) of each of 6 Tibetan pigs. The wounds in the treatment group were covered with a bilayer artificial skin (Lando) and the control wounds with vaseline gauze. In both groups, autogenous split-thickness skin were grafted to the wounds 2 weeks later (with the silicone rubber membrane removed before grafting in the treatment group). At 3 days and 2 and 10 weeks after the injury, the wounds were assessed for general condition and contraction, and tissue samples were collected from the wounds to examine the expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) using immunohistochemistry and the expressions of MMP-1 and TIMP-1 mRNA using RT-PCR.</p><p><b>RESULTS</b>At 3 days after the injury, the wounds in the 2 groups showed no significant differences in the results of any examinations. At 2 weeks after the injury, the wounds in the treatment group showed rich and more smooth granulation tissues with more regular wound edges compared with the control wounds. At 2 and 10 weeks after the injury, the wound contraction rates in the treatment group were (30.5∓3.4)% and (39.2∓2.8)%, respectively, significantly lower than the rates of (51.8∓2.6)% (t=-29.840, P=0.000) and (60.7∓2.2)% (t=-50.213, P=0.000) in the control group. At 2 weeks, the wound tissues in the treatment group expressed significantly higher levels of α-SMA (t=15.921, P=0.000) and TGF-β1 (t=29.995, P=0.000) than the control wounds, but at 10 weeks, the expressions of α-SMA (t=-41.823, P=0.000) and TGF-β1 (t=-99.777, P=0.000) in the treatment group were significantly lower than those in the control group. Compared with those in the control group, the expression of MMP-1 mRNA in the treatment group was significantly lower at 2 weeks (t=-45.412, P=0.000) but significantly higher at 10 weeks (t=78.769, P=0.000), and the expression of TIMP-1 mRNA in the treatment group was significantly lower both at 2 weeks (t=-27.064, P=0.000) and at 10 weeks (t=-40.535, P=0.000).</p><p><b>CONCLUSIONS</b>Lando dermal scaffold can promote granulation tissue growth possibly in relation with increased TGF-β1 and decreased MMP-1 expression in the wounds. This scaffold material also reduces wound contraction and lessens scar hyperplasia and contracture after wound healing, probably as a result of decreased α-SMA, TGF-β1, and TIMP-1 and increased MMP-1 expressions.</p>

Clinical observation on repairing of wounds of skin graft donor site with acellular tissue engineering dermal matrix / 中华烧伤杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of acellular tissue engineering dermal matrix (ATDM) in repairing wounds of skin graft donor site.</p><p><b>METHODS</b>Sixty patients with burn or chronic wounds hospitalized from January 2011 to April 2012 received autologous skin grafting. One wound [with size larger than 55 cm(2), and thickness of (0.33 ± 0.03) mm] out of multiple skin graft donor sites of every patient was selected, and it was divided into two parts in accordance with self-control principle. A part of wound close to the wound edge with diameter of 5 cm was taken as trial area (treated with ATDM), and the remaining wound was taken as control area (treated with vaseline gauze) according to the random number table. Blood and urine routine, liver and kidney function, and levels of IgG and IgM in blood of patients were measured one day before operation and on the 1st day after wound healing. Vital signs of patients were recorded on the operation day and the wound healing day. Gross condition of the wounds was observed during dressing change. Wound healing time was recorded. The healed wound was observed histologically. Data were processed with Log rank test or t test.</p><p><b>RESULTS</b>Leucocyte count was lowered on the 1st day after wound healing [(7.1 ± 1.2)×10(9)/L] as compared with that one day before operation [(10.1 ± 1.5)×10(9)/L, t = -12.10, P < 0.01]. The differences were not statistically significant in red blood cell count, haemoglobin level, platelet count, urine routine, levels of indexes of liver and kidney function, levels of IgG and IgM in blood between one day before operation and the 1st day after wound healing, or in vital signs (including body temperature, pulse, respiration, systolic pressure, and diastolic pressure) between the operation day and the wound healing day (with t values from -1.43 to 1.88, P values all above 0.05). No adverse effects such as abnormal exudation, itching, redness and swelling, and exanthema were observed in the wound. The median wound healing time in trial area was 12 d (95% confidence interval: 11 - 13 d), which was significantly shorter than that in control area [17 d (95% confidence interval: 16 - 18 d), χ(2) = 24.9, P < 0.01]. The healed wound of trial area was closer to the normal skin than that of control area in the shape and distribution of Fb and vascular endothelial cell, and the shape of the basilar membrane and the epidermal layer.</p><p><b>CONCLUSIONS</b>ATDM can accelerate healing of wound of skin graft donor site, and no adverse reactions were observed.</p>

Population pharmacokinetics research of clozapine in Chinese schizophrenic patients / 药学学报

The goal of this study is to investigate the population pharmacokinetics of oral given clozapine in Chinese schizophrenic patients and to identify possible relationships between population parameters and covariates including demography factors and CYP1A2 genetic polymorphism, so as to create the population pharmacokinetics model to guide individual clinical delivery. Details of drug dosage history, sampling time and concentration of 626 data points from 183 patients were collected retrospectively. The 183 patients were randomly allocated either to the index group (n = 168) or to the validation group (n = 15). Population pharmacokinetic data analysis was performed using the nonlinear mixed-effects model (NONMEM) program on the index group. The values of apparent clearance (CL/F), apparent volume of distribution (V/F) and the constant of absorption rate were estimated. A number of covariates including demographic index, coadministration of other drugs and CYP1A2 genotypes were evaluated statistically for their influence on these parameters. The final population model related clearance with day-dose/BSA (DBSA) and smoke habit (SMOK). Predictive performance of the final model evaluated with the validation group showed insignificant bias between observed and model predicted concentrations. Typical value of CL/F (non-smoking group), V/F and the constant of absorption rate were 28.5 L x h(-1) (5.05%), 1 290 L (16.7%) and 2.26 h(-1) (fixed), inter-patient variability (CV) in CL/F and V/F was) 42.2% and 10.0%, respectively. It was observed that the values of CL/F in the two smoking groups were higher than that in the non-smoking group. The residual variability (SD) between observed and model-predicted concentrations was 45.8 microg x L(-1).

Sequential management of residual wounds in burn patients / 中华烧伤杂志

<p><b>OBJECTIVE</b>To seek a sequential method for the management of residual wounds in burn patients.</p><p><b>METHODS</b>Three chronic residual wounds on each of 25 burn patients were either covered with vaseline gauze (A group), human tissue-engineered active skin (Active Skin, B group) or Active Skin after rinsing with fluid containing oxygen and vacuum assisted drainage ( C group) on wounds. The contents of (TNF)a in granulation tissue were assayed by enzyme linked immunosorbent assay (ELISA). Expression of metalloproteinase-13 (MMP-13) mRNA in granulation tissue was determined with reverse transcription polymerase chain reaction (RT-PCR). Moreover, quantity of wound bacteria in the wounds and wound healing rate were determined with usual method.</p><p><b>RESULTS</b>The quantities of wound bacteria in C group on 3,6,9, 12 post-treatment day( PTD) were (5.30 +/- 1.60), (1.30 +/-0.80) , (1.70 +/- 0. 60)and (0.60 +/-0. 10)clone formation unit/ml( CFU/ml) , respectively, which were obviously lower than those in A and B groups. The contents of TNFa and expression of metalloproteinase-13 (MMP-13) mRNA in granulation tissue in C group on 6 PTD were [ (0. 650 +/- 0. 040) ng/mg and 0. 210 +/- 0. 010,] ,respectively, and they were evidently lower than those in A group [(1.550 +/-0. 370)ng/mg,1. 040 +/- 0. 050, P <0.01] and B group (0. 810 +/- 0.080) ng/mg, 0.640 +/- 0.030, P <0.01]. Meanwhile, the contents of (TNF)a and expression of MMP-13 mRNA in B group were also obviously lower than those in A group. The wound healing ratio in C group on 15 and 30 PTD were markedly higher than those in A or B group ( P <0.01).</p><p><b>CONCLUSION</b>Covering the residual burn wounds with Active Skin after rinsing with fluid containing oxygen followed by vacuum assisted drainage can improve repairing of residual burn wounds.</p>