The effect of sepsis on wound healing.

BACKGROUND: Normal wound healing is a regulated sequence of events that successfully restore tissue integrity. Previous studies have suggested that wound healing is impaired in a septic host. The current study examines the effect of sepsis on the inflammatory and proliferative phases of wound healing at a remote site of secondary injury. METHODS: Polyvinyl alcohol sponges, either inoculated with a standard dose of Pseudomonas aeruginosa (experimental) or soaked in normal saline (control), were placed subcutaneously in the anterior abdominal region of male B6D2F1 mice. Immediately following sponge placement, full thickness excisional dermal wounds were created on the dorsum. Wound healing was examined at days 3, 5, and 7 postinjury. The infiltration of neutrophils and macrophages into wounds was quantified, and the reepithelialization rate and collagen content were measured. RESULTS: Peripheral neutrophil counts were significantly elevated in infected mice, yet neutrophil content of the remote wound of infected animals was significantly reduced (5% of control, P < 0.05). Wounds of infected mice also showed a 30% reduction in the macrophage content. Wounds of infected animals exhibited delayed reepithelialization (76 +/- 3 vs 97 +/- 3% at day 5, P < 0.05) and collagen synthesis (55.3 +/- 9.5 vs 105 +/- 13.0 microg/wound, P < 0.05). CONCLUSION: Systemic infection alters both the inflammatory and the proliferative processes at remote sites of injury. Multiple factors seem likely to contribute to the increased incidence of wound complications in septic patients.     

单纯和放射复合伤伤口愈合中外周血T淋巴细胞亚群的变化及其与愈合延迟的关系

目的研究放射复合伤口愈合中外周血T淋巴细胞亚群的变化规律及其与愈合延迟的关系.方法用碱磷酶免疫组织化学方法检测T淋巴细胞亚群.结果伤口区病理形态学观察表明,大剂量局部照射后能导致伤口愈合延迟;照射后白细胞数出现下降,伤后3～5d降低较为明显,显著低于单纯伤口组;伤后两组动物外周血T淋巴细胞及其亚群均出现降低,然而照射组始终低于单伤组,至伤后28d仍然有显著性差别.结论照射后外周血T淋巴细胞及其亚群的降低和白细胞数的下降是辐射延迟伤口愈合的重要原因     

The effect of polarized light on wound healing

. Recent investigations have reported contradictory results on the influence of low-power lasers and polarized light on wound healing. Different biologic effects have been observed after light irradiation but the real benefits of phototherapy in the healing of wounds in patients are still controversial. This article reports on a randomized, prospective single blind study that was set up to evaluate the effect of polarized light (wave length 400–2000 nm, degree of polarization >95%, power density 40 mW/cm², light energy 2.4 J/cm²) on the healing of standardized wounds. Twenty pairs of identical donor areas of split thickness skin grafts, taken on a similar location on each of the 20 patients, were treated according to an identical wound care protocol. The only difference was that one side was treated with polarized light and the other side without. The healing of these paired wounds was evaluated in a standardized manner and on a daily basis by two independent and blinded observers. The parameters assessed were: the degree of epithelialization, the quality of the granulation tissue, the degree of inflammation, the degree of infection, the aspect of the early scar tissue, blister formation, and the subjective feeling of the patient. Every parameter was scored on a 1–5 scale, with score 1 for the worst and score 5 for the best outcome. Long-term follow-up was performed after 1 month, 3 months, 6 months and 1 year. For all variables, except for infection and blister formation which was not seen in either group, highly significantly better scores were obtained in the donor sites treated with polarized light. Inter-observer agreement was acceptable to very good in all outcome variables. The results of this study demonstrated that polarized light had a beneficial effect on the healing of these standardized wounds, resulting in a faster epithelialization and an improved quality of early scar tissue formation.     

The effect of cigarette smoking on wound healing

To see if there was any difference in the skin healing of smokers as opposed to non-smokers we studied 120 women admitted consecutively for laparotomy sterilisation. The method of skin suture was standardised. We compared width, length, and colour of the scars, and assessed the overall cosmetic result using a scoring system in 69 smokers and 51 non-smokers. When the incision was in the midline the scars in the smokers measured 7.4 mm averagely as compared with 2.7 mm in non-smokers (p less than 0.02). There was a corresponding tendency in transverse incisions. When the colour was compared, 26% of smokers had light coloured scars compared with 12% of non-smokers (p less than 0.05). There were no differences between the groups when dark coloured scars were assessed. Overall, using the scoring system, smokers had significantly worse cosmetic results than non-smokers.     

The effect of 5-fluorouracil on abdominal wound healing in rats.

We carried out experiments to test the hypothesis that 5-Fluorouracil would retard wound healing when administration was started on the day of operation. Abdominal wounds were made in rats and closed again, and some of the animals were given daily 5-FU, the rest acting as controls. Test animals were killed three, five, seven and 10 days after operation, and the strength of their wounds was measured. At five and seven days the control wounds were 10 times stronger than those of the treated animals, and at 10 days they were four times stronger. We speculated that the difference in strength might be largely due to the observed fact that the muscle layer in the treated animals was considerably weaker than in the controls. We concluded that it would be unsafe to start giving 5-FU to patients immediately after operation.     

The effect of methionine on colonic wound healing in malnourished rats.

Recent studies have suggested that the healing of colonic anastomoses is impaired in malnourished subjects. It has been claimed that the healing of skin and abdominal wounds in experimental animals is improved by the administration of the essential amino acid methionine, and in the present study the effects of methionine on colonic wound healing were studied in malnourished rats. Test animals were fed a protein-free diet for 7 weeks before surgery. Methionine-treated animals received the amino acid by subcutaneous injection during the seventh week of protein deprivation and throughout the postoperative period. Anastomoses were made in the left colon, and colonic wound healing was assessed by measurements of the bursting wall tension and collagen content of anastomoses. The results were compared with those of control animals fed a normal rat diet. Protein deprivation for 7 weeks resulted in a 34% reduction in body weight, and a significant reduction in the tensile strength and collagen content of colonic anastomoses was observed. Methionine supplements had no apparent effect on these parameters of wound healing. The concept of single amino acid supplementation in cachetic patients undergoing surgery is an attractive one, but it has yet to be established that methionine supplements alone can alter the course of wound healing in such cases.     

硒化壳聚糖促创面愈合作用的体内研究

目的:研究硒化壳聚糖软膏促浅Ⅱ度烫伤小鼠创面愈合的作用。方法:147只昆明种小鼠随机分为硒化壳聚糖软膏治疗组、基质治疗组和京万红治疗组,每组49只,采用将脱毛区置于70℃恒温水浴中6s的方法制成10%体表面积浅Ⅱ度烫伤模型,伤情经病理切片证实。各组创面分别用硒化壳聚糖软膏纱布(1ml/cm2)、基质纱布(1ml/cm2)、京万红纱布(1ml/cm2)覆盖包扎固定后放回笼中饲养,换药1次/天,观察愈合时间,于伤后12h,第1、3、5、7和9天,分别处死各组小鼠7只,检测含水量、羟脯氨酸、TNF、NO、ALT,另取7只做为正常对照。结果:①创面愈合时间:硒化壳聚糖软膏组为(12.9±2.9)天、基质组为(16.3±2.1)天、京万红组为(11.8±2.4)天,硒化壳聚糖软膏组比基质组明显缩短(P<0.05);②创面含水量:伤后第1、3、5天硒化壳聚糖软膏组[(86.3±3.5)%、(77.8±3.9)%、(72.3±2.7)%]创面含水量显著低于基质组[(92.8±3.2)%、(84.9±4.2)%、(77.2±2.8)%,(P<0.05)],伤后7～9天,各组均基本恢复到正常水平;③创面TNF-α水平:伤后12h至1天达高峰,随后逐渐下降,至伤后第5天仍高于正常对照组(P<0.05);伤后12h、1天、3天、5天,硒化壳聚糖软膏组和京万红组TNF水平明显低于基质组(P<0.05);④创面组织NO含量:伤后12h各烫伤组NO含量达高峰,随后下降,至伤后第9天仍高于正常对照组(P<0.05);伤后12h、1天,硒化壳聚糖软膏组和京万红组NO含量明显低于基质组(P<0.05);⑤创面羟脯氨酸含量:伤后5、7、9天硒化壳聚糖软膏组羟脯氨酸含量显著高于基质组和京万红组(P<0.05)。结论:硒化壳聚糖软膏能有效减少烫伤后早期创面组织NO和TNF-α释放,减少渗出和水肿,晚期通过增强创面胶原合成来促进创面愈合。     

In vitro generation of helper T cells and suppressor T cells that regulate the cytolytic T lymphocyte response to trinitrophenyl-modified syngeneic cells

Helper T cells and suppressor T cells have been generated in vitro that regulate the cytolytic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified syngeneic cells. B6D2F1 helper cells generated to TNP-modified parental (P1) cells augment the CTL response to those P1-TNP-modified antigens but not to P2-TNP-modified antigens. The generation of these helper T cells requires the presence of splenic adherent cells and these helper T cells are radioresistant. A soluble factor can be obtained from the helper T cell cultures that can also augment the CTL response. The suppressor T cells generated in culture do not demonstrate the specificity observed with the helper T cells; however, they are antigen-dependent in their induction. Whether helper or suppressor activity is obtained depends upon the length of time cells are cultured in vitro.     

The effect of the germfree state on wound healing

The rate of contracture and histology of an open wound was studied in germfree and conventional rats. There were no apparent differences in the rate of wound contraction when the germfree and conventional wounds were compared, despite differences in the intensity of the inflammatory reaction. Histologically the wounds of the conventional rats demonstrated a more severe acute inflammatory reaction, more rapid formation of granulation tissue, and more rapid epithelialization of the lateral margin of the wound when compared with germfree wounds. These histologic changes did not, however, alter the rate of wound healing as determined by wound contraction.     

Fibulin-5 promotes wound healing in vivo

BACKGROUND: Fibulin-5 is a recently discovered multifunctional extracellular matrix protein that mediates endothelial cell adhesion through integrin ligation, regulates cell growth and motility in a context-specific manner, and prevents elastinopathy in vivo. Because fibulin-5 expression is induced dramatically in endothelial and smooth muscle cells in response to mechanical injury, my colleagues and I studied its role in dermal wound healing. STUDY DESIGN: We have used a gene therapy approach that used retroviral gene transfer to deliver fibulin-5 to the dermal wound milieu. Surgical generation of rabbit ear full-thickness dermal ulcers was performed in six female New Zealand white rabbits (6 months old). Wounds were injected with retrovirus containing either sense or antisense fibulin-5 or control vectors. Wounds were harvested on postwounding day 8 and analyzed by confocal microscopy, in situ hybridization, and histology. RESULTS: We report that fibulin-5 promotes wound healing in vivo. Wounds infected with fibulin-5 showed a considerable net increase (approximately 50%) in both newly formed granulation tissue volume and wound closure. Fibulin-5 expression stimulated substantial expression of collagen in dermal wounds. CONCLUSIONS: Taken together, our findings provide the first known example of overexpression of one extracellular matrix protein (fibulin-5) enhancing expression of another (type I collagen) in vivo. Our findings also demonstrate a novel role for fibulin-5 and suggest that altering extracellular matrix protein production through gene therapy may provide a novel means to promote wound healing.     

Postoperative wound suction drainage and its effect on wound healing

The positive as well as the negative effects of wound suction drainage on wound healing are outlined and the inherent physical laws which still were unclear are subject to an experimental analysis. The findings and conclusions which had been determined resulted in a modification of the clinical application practice and evidence points to the up to now daily change of suction bottle by routine as being a significant risk. Contamination of physical conditioned secretion reverse flow while opening the wound drainage system and the proven spreading ability of the bacteria within the drainage tubes leaves the possibility of a postoperative retrograde bacteria contamination reaching up to the wound site. To prophylactically reduce these risks instrumental improvements of the wound drainage system will be presented and discussed.     

The effect of rapamycin on the healing of the ureteric anastomosis and wound healing

Rapamycin is a potent immunosuppressive agent that also inhibits fibroblastic activity and therefore may affect the healing of various tissues. The aim of this study was to investigate the effect of rapamycin on wound healing and the healing of the ureteric anastomosis. Large White/Landrace pigs were subjected to a laparotomy and division and immediate anastomosis of the ureter. The animals were randomly allocated to receive either rapamycin or placebo. The animals were sacrificed on postoperative day 5, and strips of the skin and fascia closure and the ureteric anastomosis excised and used to determine the tensile strength, hydroxyproline levels, and histological changes. The tensile strength and the hydroxyproline levels in the ureter and fascia were lower in the rapamycin-treated animals. There was no difference in the tensile strength in the skin, although the hydroxyproline levels were lower. This study shows that healing of the ureteric anastomosis and fascia and skin closure may be impaired by rapamycin.     

Arginine enhances wound healing and lymphocyte immune responses in humans

Arginine has been shown to enhance wound healing and T-cell-mediated immune function in rodents. In this study the effect of oral arginine supplementation on human collagen synthesis and T-cell function was studied in 36 healthy, nonsmoking human volunteers. While volunteers were under local anesthesia, a 5 cm segment of expanded polytetrafluoroethylene tubing (1 mm outer diameter, 90 mu pore size) was inserted subcutaneously into the right deltoid region. The volunteers were then randomized into three groups that were given the following substances: (1) daily supplements of 30 gm arginine hydrochloride (24.8 gm free arginine); (2) 30 gm arginine aspartate (17 gm free arginine) daily; or (3) placebo. The supplements were given orally for 2 weeks; dietary intake was not controlled. Mitogenic responses of peripheral blood lymphocytes to phytohemagglutinin and concanavalin A were assayed at the start of study and at 1 and 2 weeks after supplementation. At 2 weeks the catheters were removed, and the amount of hydroxyproline was determined as an index of new collagen synthesis and deposition. Arginine supplementation significantly enhanced the amount of collagen deposited into a standardized wound as assessed by the amount of hydroxyproline present (10.1 +/- 2.32 nmol/cm graft in controls vs 17.57 +/- 2.16 nmol/cm in the arginine aspartate group, [p = 0.028] and vs 23.85 +/- 2.16 nmol/cm in the arginine hydrochloride group [p less than 0.001]). In parallel, arginine supplementation at both doses increased lymphocyte mitogenesis in response to phytohemagglutinin and concanavalin A. The data suggest that arginine may be of clinical benefit in improving wound healing and immune responses.     

辅助性T细胞亚群分化在Ⅲ型前列腺炎免疫发病机制中的作用

目的 探讨前列腺液(EPS)中CD+4T细胞亚群辅助性T细胞(Th细胞)分化在Ⅲ型前列腺炎免疫发病机制中的作用. 方法门诊诊断前列腺炎患者76例,年龄18～47岁,平均32岁.患者均有慢性前列腺炎典型临床症状,病程均＞3个月.按美国国立卫生院分类方法分为ⅢA型组(47例)、ⅢB型组(29例).其中ⅢA型组根据炎症程度又分为ⅢAl组(轻度炎症26例)和ⅢA2组(重度炎症21例).另设健康对照组(16例),年龄19～45岁,平均31岁.采用双抗体夹心酶联免疫法检测EPS中Th1类细胞因子(IFN-γ)、Th2类细胞因子(IL-4)水平及Th1/Th2比值(IFN-γ/IL-4),比较各组问差异.结果 ⅢA、ⅢB组IFN-γ水平[(134.78±43.67),(109.82±30.09)pg/m1]与对照组[(60.63±15.16)pg/m1]比较,差异有统计学意义(P＜0.05),ⅢA组较ⅢB组升高更明显(P＜0.05);ⅢA组IL-4水平[(51.99±20.59)pg/m1]与对照组[(53.88±17.92)pg/m1]比较差异无统计学意义P＞0.05),ⅢB组IL-4水平[(76.40±17.99)pg/m1]明显上调(P＜0.05);ⅢA组IFN-γ/IL-4水平(2.94±1.12)明显高于对照组(1.20±0.48,P＜0.05),Ⅲ B组(1.49±0.48)无明显改变(P＞0.05).与对照组比较,Ⅲ A1组IL-4水平[(63.03±18.86)pg/m1]无明显变化(P＞0.05),而ⅢA2组水平[(30.20±13.16)pg/m1]显著下调(P＜0.05);ⅢA1组和m A2组IFN-γ水平均明显上调[(127.65±36.57),(143.49±50.76)pg/m1],P＜0.05),但2组间差异无统计学意义(P＞0.05);ⅢA2组IFN-γ/IL-4明显高于ⅢA1组(3.67±0.82 vs 2.34±0.97,P＜0.05).结论 ⅢA型前列腺炎Th1细胞分化占优势,Th1/Th2平衡向Th1漂移,以细胞免疫反应为主;Th细胞分化也参与了ⅢB型前列腺炎的发病,但Th1/Th2处于相对平衡状态.Th1的优势分化可能是导致前列腺局部炎症发展的原因之一.