Effect of melatonin on wound healing in normal and pinealectomized rats

Melatonin usage is increasing gradually, but reports of its effects on wound healing are inconsistent. It has been shown that the hormone is synthesized in and secreted from the gastrointestinal system independently of the pineal gland. We have investigated, by means of a comparative study on the healing of incision and anastomotic wounds, whether melatonin has an effect on wound healing independent of the pineal gland. Rats were divided in five groups (n = 10), all of which were subjected to small intestine anastomosis. The first group (control) was otherwise untreated. Exogenous melatonin was given to the rats in second group. The calvaria was opened then closed in the third group (sham operated), whereas the fourth group was pinealectomized and the fifth group were pinealectomized and then treated with melatonin. After anastomosis bursting pressures and incision wound breaking strength were measured on the 7th postoperative day, tissue hydroxyproline levels were determined, and histopathological investigation was performed. It was found that while collagen deposition and epithelization increased concurrently in incision wounds after pinealectomy, only collagen deposition increased at the anastomosis line. Exogenous melatonin decreased collagen synthesis and epithelium proliferation and had negative effects on wound healing in both normal and pinealectomized rats.     

Effect of laser and LED phototherapies on the healing of cutaneous wound on healthy and iron-deficient Wistar rats and their impact on fibroblastic activity during wound healing

Iron deficiency impairs the formation of hemoglobin, red blood cells, as well the transport of oxygen. The wound healing process involves numerous functions, many of which are dependent on the presence of oxygen. Laser has been shown to improve angiogenesis, increases blood supply, cell proliferation and function. We aimed to study the effect of λ660 nm laser and λ700 nm light-emitting diode (LED) on fibroblastic proliferation on cutaneous wounds on iron-deficient rodents. Induction of iron anemia was carried out by feeding 105 newborn rats with a special iron-free diet. A 1?×?1 cm wound was created on the dorsum of each animal that were randomly distributed into seven groups: I, control anemic; II, anemic no treatment; III, anemic?+?L; IV, anemic?+?LED; V, healthy no treatment; VI, healthy?+?laser; VII, healthy?+?LED (n?=?15 each). Phototherapy was carried out using either a diode laser (λ660 nm, 40 mW, 10 J/cm²) or a prototype LED device (λ700?±?20 nm, 15 mW, 10 J/cm²). Treatment started immediately after surgery and was repeated at 48-h interval during 7, 14, and 21 days. After animal death, specimens were taken, routinely processed, cut, stained with hematoxylin-eosin, and underwent histological analysis and fibroblast counting. Significant difference between healthy and anemic subjects on regards the number of fibroblast between treatments was seen (p?<?0.008, p?<?0.001). On healthy animals, significant higher count was seen when laser was used (p?<?0.008). Anemic subjects irradiated with LED showed significantly higher count (p?<?0.001). It is concluded that the use of LED light caused a significant positive biomodulation of fibroblastic proliferation on anemic animals and laser was more effective on increasing proliferation on non-anemics.     

Effects of exosomes derived from fibroblast cells on skin wound healing in Wistar rats

BackgroundThe role of exosomes in areas, such as skin wound healing, have been of consideratble interest recently. However, the effects of exosomes derived mainly from fibroblast cells on wound healing have yet to be documented well. The study aimed to evaluate the effects of exosomes derived from fibroblast cells on wound healing in Wistar rats.MethodsHuman fetal skin was isolated afterward centrifuge, and trypsin 0.1% was added to the cells after removing DPBS from the Falcon tube, and the trypsin was removed. The cells were moved to culture flasks. Then, the secondary culture of Human Fetal Skin Fibroblast was done. The pellets containing exosomes were suspended in PBS, and to achieve purified exosomes, the suspended Exosome were passed through a 0.22 µm filter. The exosome solution was kept at − 20 ºC. In the in vivo phase, 48 male Wistar rats were divided into four groups. Group I, low-dose exosome (LDE) solution (150 μl/day), group II high-dose exosome (HDE) solution (300 μl/day), group III commercially available ointment (positive control (PC)) was topically applied on wounds and group VI without treatment (negative control (NC)). A skin biopsy was taken for histopathological analysis. Wound area, depth of ulcer, degree of granulation, and inflammation were assessed. For histopathological assessment, re-epithelialization, inflammatory cells, granulation tissue, crust formation, and collagen maturation (fibrosis) parameters were evaluated.ResultsForty-eight male Wistar rats were included. The HDE group's showed accelerated healing compared to the NC and PC groups at 9 and 12 days. Inflammation and granulation were higher in the HDE, LDE, and PC groups than in the NC group (p < 0.05). The onset of re-epithelialization and collagen deposition was higher in the LDE, HDE, and PC groups, then on nine and 12-day, gradually maturing and extending through the ulcer (p < 0.05). On day 12, in almost all parameters, the LDE and HDE groups showed improved results compared to NC cases (p < 0.05).ConclusionsThe results showed that the utilization of fibroblast-Exo significantly promoted cutaneous wound healing in a rat full-thickness skin ulcer model. This is a potential innovation for cell-free therapy from fibroblast-Exo as a closed structure similar to human cells.     

Effect of supplemental zinc on wound healing in rats

Two experiments were carried out to determine the effect of supplemental oral zinc on wound healing in a normal rat. No evidence of beneficial effects was found. Measured wounds healed at the same rate, and the wound hydroxyproline level tended to be lower in the animals receiving zinc. There was also no evidence that the rat even incorporates excess zinc in tissues.     

去神经支配对大鼠创面愈合的影响

目的通过制备去神经支配大鼠创面模型,观察去神经大鼠创面愈合率、创面血管和皮肤增殖改变情况,为去神经创面Ⅹ合机制提供理论依据。方法分离并切断SD大鼠胸9～腰1右侧脊神经,造模后在背部对称制作两个直径为1.0cm的圆形创面,分别观察两侧创面愈合时间、创面大体和组织形态学、创面细胞增殖活性、创面修复过程中血管再生情况,并对数据进行统计学分析。结果实验组愈合时间在4周,对照组为3周;实验组创面上皮化速度慢于对照组;实验组愈合表皮层较薄,上皮细胞大小不一;愈合时真皮和表皮层细胞增殖活跃,2～4周时实验组增殖活性低于对照组(P0.05);创面微血管主要分布于真皮层,密度随Ⅹ合时间增加,但2～4周实验组表现较对照组弱(P0.05)。结论去神经后皮肤创面细胞增殖低下,愈合时间延长,血管再生现象受到抑制。     

The effect of testosterone propionate on wound healing in normal and castrate rats

The dependence of wound healing on testosterone was studied in normal and castrate rats by determination of wound breaking strength (WBS) in dermal wounds, by implantation of subcutaneous polyvinyl sponges (PVS) and by [³H]proline tracer studies. The level of testosterone achieved with various doses of testosterone propionate (TP) was assessed using the androgenic effect of this hormone on prostate and seminal vesicle weights. Exogenous testosterone propionate (0.25 – 3.0 mg/day) produced no acceleration of wound healing as measured by WBS on 14- and 21-day wounds. In castrate rats a mild inhibition of healing (15% decrease in WBS) was found in 14-day wounds but no difference was found between castrate and control in 21-day wounds. The rate of wound collagen synthesis was assessed by measuring the conversion of [³H]proline to [³H]hydroxyproline, a process essentially limited to procollagen synthesis. It was not altered by castration, or by administration of testosterone propionate (0.0625 – 1.0 mg/day) to castrate rats. Similarly, deposition of tissue in polyvinyl sponges whether measured as added dry weight or total hydroxyproline did not differ significantly between control and castrate rats receiving testosterone propionate (0–1.0 mg/day). As a method of assessing wound healing, WBS measurements produced the most consistent results. In conclusion, no longterm dependence of wound healing on testosterone was identified in the testosterone-depleted (castrate) rat although some early depression was noted, and no acceleration of the normal process resulted from exogenous testosterone administration in the normal or testosterone-depleted rat.     

Comparison of the effects of collagenase and extract of Centella asiatica in an experimental model of wound healing: An immunohistochemical and histopathological study

In this study, we compared the effects of collagenase and Centella asiatica in the rat model. Twenty‐seven female rats were divided into three groups, and two full‐thickness wounds were made for each animal. Collagenase ointment was applied topically to Group I and C. asiatica ointment to Group II rats. In Group III, no treatment was applied. On the third day of treatment, wounds on the left side of three animals of each group were excised. On the fifth and eighth day of the treatments, the same procedure was performed for the remaining animals. Indirect immunohistochemical examination was performed to detect transforming growth factor beta (TGF)‐β, endothelial and inducible nitric oxide synthase (eNOS and iNOS), vascular endothelial growth factor, TGF‐α, laminin, fibronectin, collagen I, and interleukin‐1β. According to the measurements of the wound areas and wound healing periodo, collagenase was superior to the control group. Immunohistochemical examinations showed strong (+++) iNOS and TGF‐β immunoreactivities in C. asiatica group. eNOS immunoreactivity was moderate (++) in this group. For the collagenase group, iNOS, eNOS, and TGF‐β immunoreactivities were moderate (++). In the collagenase group, while TGF‐β and iNOS immunoreactivities were weaker, laminin and fibronectin reactivities were stronger than in C. asiatica and control groups. Collagenase was superior to C. asiatica according to the immunohistochemical findings. Collagenase ointment significantly improves the quality of wound healing and scar formation and is a more appropriate treatment choice than extract of C. asiatica in the early stages of the wound healing process.     

Oral l‐glutamine administration attenuated cutaneous wound healing in Wistar rats

The objective of this study was to evaluate the wound healing potential of l ‐glutamine in laboratory rats using excision and incision wound models. Excision wounds of size 500 mm² and depth 2 mm were made on the dorsal portion of male Wistar rats (230–250 g) and were used for the study of oral l ‐glutamine (1 g/kg) treatment on the rate of contraction of wound and epithelisation. Histological evaluation of wound tissue was also performed. Six‐centimetre‐long two linear‐paravertebral incisions in male Wistar rats (230–250 g) were used to study the effect of l ‐glutamine (1 g/kg, p.o.) treatment on tensile strength, total protein and hydroxyproline content in the incision model. Oral administration of l ‐glutamine (1 g/kg) significantly decreased wound area, epithelisation period and wound index, whereas the rate of wound contraction significantly increased (P < 0·001) when compared with vehicle control rats in the excision wound model. Tensile strength, hydroxyproline content and protein level were significantly increased (P < 0·001) in l ‐glutamine (1 g/kg, p.o.)‐treated rats when compared with vehicle control rats in the incision wound model. Histological evaluation of wound tissue from l ‐glutamine (1 g/kg, p.o.)‐treated rats showed complete epithelialisation with new blood vessel formation and high fibrous tissues in the excision wound model. In conclusion, oral administration of l ‐glutamine (1 g/kg) promotes wound healing by acting on various stages of wound healing such as collagen synthesis, wound contraction and epithelialisation.     

Wound healing in normal and analbuminemic (NAR) rats

It has been suggested by several investigators that hypoalbuminemia results in impaired wound healing. In most studies, however, hypoalbuminemia is a manifestation of malnutrition or underlying liver disease. In this study, we examined the effect of isolated hypoalbuminemia on wound healing. Analbuminemic (NAR) rats which are Sprague-Dawley mutants with trace levels of plasma albumin due to a defect in albumin synthesis were studied. Adult NAR and Sprague-Dawley rats (n = 10 each) underwent a 7 cm dorsal skin incision and implantation of a polyvinyl alcohol sponge subcutaneously under pentobarbital anesthesia. Seven days postoperatively all rats were killed with ether, the wounds were excised, and breaking strength was measured. Sponge hydroxyproline content was determined colorimetrically. There were no significant differences in wound breaking strength (fresh or formalin fixed) or sponge collagen content between the Sprague-Dawley and analbuminemic rats. We conclude that isolated hypoalbuminemia has no detrimental effect on would healing in rats.     

不同浓度法舒地尔促进皮肤创面愈合作用的研究

目的：观察法舒地尔（HA1077）促进创面愈合的效果,并探讨HA1077与创面愈合的量效关系,寻找出促进创面愈合的最佳剂量。方法：18只Wistar大鼠背部左右两侧致直径为2cm的圆形皮肤缺损。随机3只动物6个创面为一组,分为6组,分别给予10、20、40、80和160μmol/L盐酸法舒地尔和生理盐水（对照组）创面喷洒,每个创面0.5ml,隔日创面追加喷洒。实验3、7、10d计算伤口面积,实验10d取创面组织,观察组织学变化。结果：各组大鼠创面面积随伤后时间延长而逐渐缩小,20μmol/L组创面面积明显小于同时间点其他各组,除实验7d与80μmol/L组创面面积比较差异无显著性外,其余各时间点差异均有显著性（P〈0.05）。病理学变化显示,创伤后10d,应用20μmol/L法舒地尔组创面新生肉芽组织生长及新生表皮生长速度明显优于其他各组。结论：HA1077可促进皮肤缺损创面愈合,以20μmol/LHA1077效果更为明显。     

Effect of plasma fibronectin on the incisional wound healing in rats

BACKGROUND: Abdominal wall repair after celiotomy is important because insufficient incisional wound strength results in wound failures such as fascial dehiscence and herniation. Plasma fibronectin (pFn) has been shown to play an important role in wound healing. The purpose of this study was to investigate whether pFn improves incisional wound healing in a rat skin incision and celiotomy model. METHODS: Rats underwent a linear skin incision in the dorsal plane or a full-thickness incisional wound (celiotomy) in the abdominal wall. The same operative procedures were performed on rats whose pFn levels were reduced by antirat pFn serum. The wounds were sutured, and purified human pFn or albumin was given intravenously. RESULTS: After the celiotomy, pFn levels decreased immediately and reached a minimum at 3 h after incision. A single injection of pFn (10 mg/kg) significantly increased the breaking strength of the skin and the bursting pressure of the abdominal wall. The amount of hydroxyproline in the skin incisional wound with pFn was significantly greater than with an injection of albumin as control. In rats with pFn levels decreased by antirat pFn serum, a single administration of pFn significantly increased the breaking strength of the skin and the bursting pressure of the abdominal wall compared to a control injection of albumin. CONCLUSIONS: It is important for wound healing to maintain sufficiently high levels of pFn. A single intravenous injection of pFn after celiotomy may be useful in the prevention of fascial dehiscence and herniation.     

Myofibroblasts and colonic anastomosis healing in Wistar rats

Background  

The myofibroblasts play a central role in wound healing throughout the body. The process of wound healing in the colon was evaluated with emphasis on the role of myofibroblasts.     

复方紫归膏促进大鼠创面愈合的实验研究

目的：探讨外用中药复方紫归膏（Compound-ZiGui Cream,CZGC）促进大鼠皮肤创面愈合的作用及机制。方法：取SD大鼠125只,建立大鼠创伤模型。实验分成A、B、C、D、E共5组,每组25只。A组为模型组,B组为京万红对照组,C、D、E组分别为复方紫归膏高、中、低药物浓度剂量组。分别于伤后3、7、10、14天时间点观测创面愈合率、HE常规染色显微镜下新生肉芽组织厚度及其形态学改变情况,最后观测创面平均愈合时间等。结果：B、C、D、E组第7、10、14天创面愈合率均优于A组（P〈0.01）,C、D组第7、10天创面愈合率优于B组（P〈0.05）;B组第7、14天创面愈合率较E组优（P〈0.01）;B、C、D、E创面愈合时间均优于A组（P〈0.01）;C、D组优于B组（P〈0.01）;B组和E组间创面愈合时间无差异（P〉0.05）。伤后第7、10天,B、C、D组肉芽组织厚度均较A组厚（P〈0.01）,E组第7、14天较A组厚（P〈0.05）,B组较E组厚（P〈0.01）。组织病理图像分析,伤后第7天,B、C、D、E组新生毛细血管数、毛细血管总面积、面密度、数密度和周密度较A组均有明显提高（P〈0.05或0.01）,且C、D组作用优于B组（P〈0.05或0.01）。B组优于E组（P〈0.05）。结论：外用中药复方紫归膏能促进皮肤创面愈合,其可能机制是促进新生毛细血管的增殖,促进肉芽组织生长。     

Role of fibronectin in normal wound healing

Fibronectin is an adhesive molecule that plays a crucial role in wound healing, particularly in extracellular matrix (ECM) formation and also in reepithelialisation. Fibronectin plays many different roles in the wound healing process because of the presence of specific function domains and binding sites in its structure. Fibronectin interacts with different cell types, cytokines and the ECM. The main role of fibronectin is ECM formation. First, plasma fibronectin forms a provisional fibrin–fibronectin matrix, which will later be replaced by the mature ECM‐containing tissue fibronectin.     

Myofibroblasts and colonic anastomosis healing in Wistar rats

Background

Mesh repair of incisional hernia is superior to the conventional technique. From all available materials for open surgery polypropylene (PP) is the most widely used. Development resulted in meshes with larger pore size, decreased mesh surface and lower weight. The aim of this retrospective non randomized study was to compare the quality of life in the long term follow up (> 72 month) after incisional hernia repair with "light weight"(LW) and "heavy weight"(HW) PP meshes.

Methods

12 patients who underwent midline open incisional hernia repair with a HW-PP mesh (Prolene^® 109 g/m² pore size 1.6 mm) between January 1996 and December 1997 were compared with 12 consecutive patients who underwent the same procedure with a LW-PP mesh (Vypro^® 54 g/m², pore size 4-5 mm) from January 1998. The standard technique was the sublay mesh-plasty with the retromuscular positioning of the mesh. The two groups were equal in BMI, age, gender and hernia size. Patients were routinely seen back in the clinic.

Results

In the long term run (mean follow up 112 ± 22 months) patients of the HW mesh group revealed no significant difference in the SF-36 Health Survey domains compared to the LW group (mean follow up 75 ± 16 months).

Conclusions

In this study the health related quality of life based on the SF 36 survey after open incisional hernia repair with light or heavy weight meshes is not related to the mesh type in the long term follow up.     

Efficacy of Jasminum grandiflorum L. leaf extract on dermal wound healing in rats

Wound healing is a fundamental response to tissue injury and natural products accelerate the healing process. Here, we have explored the efficacy of topical administration of an ointment, prepared by methanolic extract of Jasminum grandiflorum L. (Oleaceae) leaves, on cutaneous wound healing in rats. The topical application of the Jasminum ointment on full thickness excision wounds accelerated the healing process. Tissue growth and collagen synthesis were significantly higher determined by total hydroxyl proline, hexosamine, protein and DNA content. The response was concentration‐ and time‐dependent, when observed on days 4, 8 and 12 after wound creation. The rate of wound healing was faster as determined by wound contraction, tensile strength and other histopathological changes. In addition, this ointment also raised the activity of superoxide dismutase (SOD) and catalase (CAT) with high GSH content and low lipid peroxidation products in wound tissue. Thus, it could be suggested that the ointment from the methanolic extract of J. grandiflorum leaf improves the rate of wound healing by enhancing the rate of collagen synthesis and also by improving the antioxidant status in the newly synthesised healing wound tissue.