Topical N-Acetylcysteine Improves Wound Healing Comparable to Dexpanthenol: An Experimental Study

In this study, we aimed to compare the effects of dexpanthenol and N-acetylcysteine on wound healing. The wound healing process is a multifaceted sequence of activities associated with tissue restoration process. A number of investigations and clinical studies have been performed to determine new approaches for the improvement of wound healing. A total of 30 rats were divided into 3 equal groups. A linear 2-cm incision was made in the rats'' skin. No treatment was administered in the first (control) group. Dexpanthenol cream was administered to the rats in the second group and 3% N-acetylcysteine cream was administered to the rats in the third group. The wound areas of all of the rats were measured on certain days. On the 21st day, all wounds were excised and histologically evaluated. The epithelialization and granulation rates between the groups were revealed to be similar in microscopic evaluations. Although the fibrosis was remarkable in the control group as compared with the other groups, it was similar in N-acetylcysteine and dexpanthenol groups. Angiogenesis rate was remarkable in the N-acetylcysteine group compared with the others. In multiple-comparison analysis, Dexpanthenol and N-acetylcysteine groups had similar results in terms of wound healing rates (P < 0.05), which were both higher than in the control group (P > 0.05). The efficacy of N-acetylcysteine in wound healing is comparable to dexpanthenol, and both substances can be used to improve wound healing.Key words: N-acetylcysteine, Dexpanthenol, Wound healingWound healing is a multifaceted sequence of activities associated with the tissue restoration process.¹ This activity takes place in 4 main steps: inflammation, proliferation, matrix deposition, and remodeling.^2,3 Moreover, there are many factors that might have harmful effects on the wound healing process. In this regard, there have been numerous analyses and clinical studies aiming to find new methods for the improvement of wound healing processes.⁴Dexpanthenol is the biologically-active alcohol of pantothenic acid, which leads to an elevation in the amount of coenzyme A in the cell. Dexpanthenol is extensively used in topical form, since it can easily penetrate the skin even at large local concentrations. When used in formulations, dexpanthenol is most effective for the stimulation of epithelialization, granulation, and the mitigation of itching.⁵N-acetylcysteine (NAC) is a prodrug that supplies bioavailable cysteine for glutathione replenishment and prevents oxidative damage as well as inflammation. It also leads to glutathione (GSH) formation in the body. Besides fostering angiogenesis, it is used to scavenge free radicals. NAC has a number of functions in the stages of repair process, including cell proliferation, migration, and scratch wound healing. Moreover, NAC has also been reported to promote wound healing in diabetic rats.⁶In this study, we aimed to compare the effects of dexpanthenol, a molecule that is widely used to improve wound healing, and NAC, a molecule that reduces oxidative stress and inflammation, on wound healing.     

Characterization of a novel standardized human three‐dimensional skin wound healing model using non‐sequential fractional ultrapulsed CO2 laser treatments

Background and Objective

At present, there is no standardized in vitro human skin model for wound healing. Therefore, our aim was to establish and characterize an in vitro/ex vivo three‐dimensional (3D) wound healing model, which we employed to analyze the effects of dexpanthenol on wound healing and gene regulation.

Materials and Methods

The novel human 3D skin wound healing model using scaffold and collagen 3D organotypic skin equivalents was irradiated with a non‐sequential fractional ultrapulsed CO₂ laser. These standardized injured full‐thickness skin equivalents enable qRT–PCR, microarray, and histological studies analyzing the effect of topically or systemically applied compounds on skin wound healing.

Results

These human laser‐irradiated skin models were found to be appropriate for in vitro wound healing analysis. Topical treatment of skin wounds with a 5% dexpanthenol water‐in‐oil emulsion or two different 5% dexpanthenol oil‐in‐water emulsions clearly enhanced wound closure compared to laser‐irradiated untreated control models. To find out whether this positive effect is caused by the active substance dexpanthenol, laser‐irradiated skin models were cultured in calciumpantothenate containing medium (20 μg/ml) compared to skin equivalents cultured without calciumpantothenate. 3D models cultured in calciumpantothenate revealed considerably faster wound closure compared to the control models. Quantitative RT–PCR studies showed enhanced mRNA expression of MMP3, IL1α, keratin‐associated protein 4–12 (KRTAP4–12), and decreased expression of S100A7 in laser‐irradiated skin models cultured in medium containing calciumpantothenate.

Conclusion

This novel standardized human 3D skin wound healing model proves useful for topical pharmacological studies on wound healing and reveals new insights into molecular mechanisms of dexpanthenol‐mediated effects on wound healing. In addition, these novel 3D model systems can be used to monitor ex vivo effects of various laser systems on gene expression and morphology of human skin. Lasers Surg. Med. 47:257–265, 2015. © 2015 Wiley Periodicals, Inc.     

Avocado/soybean unsaponifiables: a novel regulator of cutaneous wound healing,modelling and remodelling

We investigated the effects of avocado/soybean unsaponifiables (ASU) on the healing response of cutaneous wound defect in rats. Sixty male rats were randomly divided into three groups including control, vehicle and treatment (n = 20 in each group). A 2 × 2 cm² wound defect was made on the dorsum. The control, vehicle and treatment groups were treated daily with topical application of saline, cream and cream/ASU for 10 days, respectively. The wounds were monitored daily. The animals were euthanised at 10, 20 and 30 days post injury (D). The dry matter, hydroxyproline, collagen, n‐acetyl glucosamine (NAGLA) and n‐acetyl galactosamine (NAGAA) contents of the skin samples were measured and the histopathological and biomechanical characteristics of the samples were investigated. Statistics of P < 0·05 was considered significant. Treatment significantly increased tissue glycosaminoglycans and collagen contents at various stages of wound healing compared to controls. Treatment modulated inflammation, improved fibroplasia and produced high amounts of scar tissue at short term. At long term, treatment reduced the scar tissue size and increased the quality and rate of wound contraction and reepithelisation compared to controls. The treated lesions were more cosmetically pleasing and had significantly higher biomechanical characteristics than controls. ASU was effective in rat wound healing.     

Effects of tretinoin on wound healing in aged skin

Aged and adult populations have differences in the structural, biological, and healing properties of skin. Comparative studies of healing under the influence of retinoids in both these populations are very important and, to the best of our knowledge, have not been performed to date. The purpose of this study was to compare the activities of topical tretinoin in aged and adult animal models of wound healing by secondary intention. Male aged rats (24 months old, n = 7) and adult rats (6 months old, n = 8) were used. The rats were assigned to the following groups according to the dates on which wound samples were excised (day 14 or 21 after model creation): treated group, control group, and naive group. Topical application of tretinoin cream was used only on the proximal wound and was applied daily for 7 days. Wound healing areas were measured using metal calipers, and morphological analysis was performed. Slides were stained with Hematoxylin and Eosin, Masson's trichrome, and periodic acid‐Schiff stains. Statistical analysis adopted a 5% coefficient for rejection of the null hypothesis. Although aged animals showed skin repair, complete reepithelialization was found on day 21 in some animals of both groups (treated and control). In aged rats, the wound area was significantly smaller in treated wounds than in untreated wounds, resulting in a larger scar area compared with the adult group. When treated wounds were compared, no differences were found between the wound areas in adult and aged rats. As expected, the collagen concentration was higher in normal skin from adult rats than in normal skin from aged animals, but there was no difference when aged skin was treated with tretinoin. These results indicate that tretinoin increases collagen synthesis in aged skin and returns the healing process to a normal state of skin healing.     

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。     

Comparison of the effects of gabapentin and pregabalin on wound healing in rats

Gabapentinoids are effective adjunct drugs for reducing postoperative pain. However, the effects of gabapentinoids on wound healing have not been evaluated yet. In this study we evaluated their effects on wound healing. A total of 17 male Wistar‐Albino rats, 250–350 g, were divided into three groups randomly: control group (n = 5, 2 ml saline), gabapentin group (n = 6, 20 mg/kg gabapentin) and pregabalin group (n = 6, 20 mg/kg pregabalin). Until day 13 inflammation scores were significantly lower (P < 0·05) and wound healing was significantly better in the control group when compared with gabapentin and pregabalin groups (P < 0·001). Inflammation scores were significantly lower in pregabalin group when compared with gabapentin group until day 13. But wound healing was significantly better in gabapentin group than in pregabalin group between days 13 and 21. In conclusion when gabapentin and pregabalin were compared, although pregabalin decreases inflammation scores, gabapentin has better results in wound healing.     

The usefulness of carvedilol and nebivolol in preventing contrast nephropathy in rats

Abstract

Background: Oxidative stress and vasoconstriction appear to be important components of contrast nephropathy (CN) pathogenesis, and both carvedilol and nebivolol are known to have vasodilatory and antioxidant effects. Aims: This study aimed to investigate whether carvedilol and nebivolol play preventive roles against developing CN and to compare the effects of each. Materials and methods: Wistar albino rats were divided into control (C, n?=?6), contrast material (CM, n?=?6), carvedilol (CV, n?=?7), carvedilol?+?contrast material (CV?+?CM, n?=?7), nebivolol (N, n?=?7), and nebivolol?+?contrast (N?+?CM, n?=?7) groups. Following 3 days of dehydration, 6?mL/kg diatrizoate was administered to each rat. Carvedilol was given at a dose of 2?mg/kg and nebivolol at a dose of 1?mg/kg by way of oral gavage. After scarification, total antioxidant capacity (TAC), malondialdehyde (MDA), and superoxide dismutase (SOD) were studied in renal tissue. Histopathological findings were graded as mild (+), moderate (++), and severe (+++). Results and discussion: Most of the histopathological findings and MDA levels were significantly higher in the CM group than that in the C, CVCM, and NVCM groups, whereas there was no significant difference between the C, CVCM and NVCM groups. TAC level in the CM group was significantly lower than in all other groups. There was no difference in SOD among groups. Conclusions: Carvedilol and nebivolol both prevent development of nephropathy related to CMs by decreasing oxidative stress. Neither is superior to the other.     

Benign Mucinous Cystadenoma of the Appendix Report of 3 Cases. Review of the Literature

Backgrounds/Aims: Inflammation during the early phase of anastomotic wound healing is an essential cellular response and is suppressed by corticosteroids. The anti-inflammatory effect of corticosteroids is largely responsible for its impairment of wound healing in bowel anastomosis. Beta-D-glucan, a commonly used macrophage activator, has been shown to improve anastomotic wound healing under normal conditions. In the present study, we have investigated the effects of beta-D-glucan on anastomotic wound healing in rats treated with long-term corticosteroid. Methodology: 92 male Sprague-Dawley rats were randomized into four groups. 1: control, 2: control + beta-D-glu-can, 3: steroid, 4: steroid + beta-D-glucan. Methylprednisolone (5mg/kg) was injected IM daily for 14 days in groups 3 and 4. After 14 days, following anaesthesia and laparotomy, colonic anastomosis was performed 3 cm away from the peritoneal reflection of rectum. In groups 2 and 4, 100mg/kg beta-D-glucan was administered orally for 7 days before laparotomy. On postoperative day 3, relaparotomies were performed and bursting pressures, hydroxyproline levels and histopathological specimens were studied.

Results: The mean values of bursting pressures groups were 50.8 (95% CI 46.99-56.50), 58.2 (95% CI 54.49-61.90), 32.0 (95% CI 29.21-34.98), 45.9 (95% CI 43.09-48.80) respectively. The differences of the mean values of the groups between group 1 and 2 and also 3 were significant (p = 0.002, p < 0.001). The mean values of hydroxyproline of the groups were 3.8 (95% CI 3.56-4.06), 4.7 (95% CI 4.50-5.04), 2.9 (95% CI 2.73-3.20), 3.9 (95% CI 3.65-4.22) respectively. The differences of the values of the groups between control (group1) and group 2 and also group 3 were significant (p = 0.001, p < 0.001). In histopathological examination, increased macrophages and fibroblast population were observed in specimens from beta-D-glucan-treated animals.

Conclusion: The results indicate that in rat model, oral administration of beta-D-glucan causes a significant improvement in the healing of anastomotic wound impaired by long-term corticosteroid administration.     

Wound‐healing potential of an ethanol extract of Carica papaya (Caricaceae) seeds

Carica papaya L. (Linn) (Caricaceae) is traditionally used to treat various skin disorders, including wounds. It is widely used in developing countries as an effective and readily available treatment for various wounds, particularly burns. This study evaluated the wound‐healing and antimicrobial activity of C. papaya seed extract. Ethanol extract of C. papaya seed (50 mg/kg/day) was evaluated for its wound‐healing activity in Sprague‐Dawley rats using excision wound model. Animals were randomly divided into four groups of six each (group 1 served as control, group 2 treated with papaya seed extract, group 3 treated with a standard drug mupirocin and papaya seed extract (1:1 ratio) and group 4 treated with a mupirocin ointment. Rate of wound contraction and hydroxyproline content were determined to assess the wound‐healing activity of the seed extract. The group 2 animals showed a significant decrease in wound area of 89% over 13 days when compared with groups 1 (82%), 3 (86%) and 4 (84%) respectively. The hydroxyproline content was significantly higher with the granulation tissue obtained from group 2 animals which were treated with C. papaya seed extract. Histological analysis of granulation tissue of the group 2 animals showed the deposition of well‐organized collagen. The extract exhibited antimicrobial activity against Salmonella choleraesuis and Staphylococcus aureus. Our results suggest that C. papaya promotes significant wound healing in rats and further evaluation for this activity in humans is suggested.     

Wound tensile strength and contraction rate are not affected by laparotomy or pneumoperitoneum

Background: Many cellular elements responsible for wound healing are affected by laparotomy. The aim of this study was to evaluate the effects of laparotomy and CO₂ pneumoperitoneum on wound healing. Methods: Male Sprague Dawley rats were randomly assigned to one of three experimental groups. Anesthesia control rats underwent no procedure. Pneumoperitoneum group rats were insufflated with CO₂ gas. Laparotomy group rats underwent a 7-cm midline laparotomy incision. The interventions were 30 min long. For the incisional study (n= 30), a 4-cm dorsal full-thickness skin incision was made on each rat and then closed with staples. On postoperative days 7 and 14, an equal number of rats were sacrificed from each group, and wound tensile strength measurements were performed. For the excisional study (n= 45), each group of 15 rats underwent a 2-cm diameter circular dorsal full-thickness skin excision. Blinded measurements of wound area were performed every other day until wounds closed. Results: Wound tensile strength values were not significantly different among experimental groups at either time point. The study had a power of 80% to find a 30% difference at POD 7 and a power of 80% to find a 23% difference at POD 14 to a confidence level of p < 0.05. Wound contraction data from the excisional model were analyzed with the Generalized Estimation Equations statistical approach. When we modeled the treatment group as a covariate, no statistical difference was found between groups, demonstrating equal slopes across time. Conclusions: From the results of these studies, we conclude that wound healing in this model is not significantly diminished following laparotomy or peritoneal insufflation, as compared to anesthesia control. Received: 26 September 1997/Accepted: 27 January 1998     

Hypoandrogenism related to early skin wound healing resistance in rats

The purpose of this study was to verify the effect of testosterone depletion on healing of surgical skin wounds at different ages and post‐operative periods. Forty‐four Wistar male rats were divided into four groups: Group 1Y (n = 11) – young control, sham‐operated rats (30‐day old); Group 1A (n = 10) – adult control, sham‐operated rats (3 to 4‐month old); Group 2Y (n = 10) – young rats after bilateral orchiectomy; and Group 2A (n = 11) – adult rats after bilateral orchiectomy. After 6 months, a linear incision was performed on the dorsal region of the animals. The resistance of the wound healing was measured in a skin fragment using a tensiometer, on the 7th and 21st post‐operative days. The wound healing resistance was higher in Group 1Y than in Group 2Y after 7 days (P < 0.05). Wound healing resistance at 21 days was higher than at 7 days in all groups (P < 0.05). Late wound healing resistance was not different between young and adult rats. It is concluded that bilateral orchiectomy diminished the wound healing resistance only in young animals at the 7th post‐operative day.     

Functional characterisation of bioactive peptide derived from terrestrial snail Cryptozona bistrialis and its wound‐healing property in normal and diabetic‐induced Wistar albino rats

A peptide might be an exciting biomaterial or template for the development of novel wound‐healing agents. In this report, it was isolated from the terrestrial snail Cryptozona bistrialis by enzymatic digestion and was evaluated for its in vitro wound‐healing activity in NIH/3T3 mouse fibroblasts cell line and in vivo wound‐healing activity in normal and diabetic‐induced Wistar albino rats. The C. bistrialis protein was digested by the papain enzyme, and 21.79 kDa peptide (Cb‐peptide) was purified by reversed‐phase high‐performance liquid chromatography and identified by MALDI (matrix‐assisted laser desorption/ionization)‐TOF analysis. The isolated Cb‐peptide was characterised by various analytical methods. The peptide demonstrated a capacity to prevent the development of pathogenic bacterial and fungal cultures and proved that it promotes significant wound‐healing activity in the wound scratch assay method by rapid cell migration and closure of wound. Isolated Cb‐peptide was lyophilised and formulated to ointment and analysed for in vivo wound‐healing activity in normal and diabetic (alloxan monohydrate)‐induced Wistar albino rats. Cb‐peptide ointment‐treated groups showed a greater degree of wound healing and early and complete period of epithelialisation in normal and diabetic‐induced Wistar albino rats. Cb‐peptide ointment‐treated groups showed significant excision and incision wound‐healing activity. A conclusion was reached that the peptide isolated from C. bistrialis showed greater wound‐healing activity compared with vehicle control and standard control.     

Effects of Hyperbaric Oxygen and Preconditioning on Wound Healing in Colonic Anastomoses

Aim: The purpose of this study was to evaluate the effects of hyperbaric oxygen (HBO) and HBO preconditioning (pre-HBO) on experimental wound healing and tensile strength in the colonic anastomosis of rats. Materials and Methods: A total of 21 Sprague–Dawley rats were divided into three random groups of equal numbers: sham operation, pre-HBO, and HBO. Sham group was given standard left colon resection and end-to-end anastomosis; pre-HBO group received HBO as one dose + colonic resection + anastomosis; HBO group was given colonic resection + anastomosis + HBO. HBO was administrated at 24-hr intervals and relaparatomy was performed on the fifth day. Malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNF-α), and hydroxy (OH)-proline levels and anastomotic burst pressure were evaluated. Results: Burst pressure and OH-proline levels markedly increased in the HBO group compared with the sham and pre-HBO groups. When compared with the sham group, MDA and MPO levels were significantly decreased in the HBO and pre-HBO groups. In contrast to these findings, SOD and GSH-Px levels were increased in the HBO group as compared with the sham and pre-HBO groups. TNF-α, IL-6, and IL-10 values were detected at low levels in the HBO group as compared with other groups. Conclusions: HBO administration accelerated wound healing and strengthened the anastomotic tissue. In the light of these results, the HBO administration has beneficial effects and contributed to wound healing in colonic anastomosis. But, as expected, pre-HBO did not alter the results significantly.     

Effects of induction therapy on wound healing at bronchial anastomosis sites in rats

Objectives: Preoperative chemotherapy is frequently used for advanced lung cancer. As a valid alternative to pneumonectomy, bronchoplasty has the advantage of enabling lung parenchyma function to be preserved. The effects of antineoplastic agents on healing bronchial anastomosis remain unclear. We studied the effects of preoperative chemotherapy on wound healing in bronchial anastomoses and clarified causes of wound healing impairment in rats. Methods: In experiment I, at 3 days before surgery, rats were injected with cyclophosphamide, doxorubicin, and vincristine (CAV group) or cisplatin and etoposide (PVP treated rats). In experiment II, at 48 hrs before surgery, rats were treated with rabbit antirat macrophage serum and antirat monocyte chemoattractant protein-1 antibody to inhibit macrophage infiltration. On days 3, 5, and 7 after bronchus anastomosis, wound healing was assessed by examining bursting strength and hydroxyproline tissue content. Results: CAV-treated rats showed significant impaired wound healing, marked severe leucopenia, and reduced macrophage infiltration. The PVP group showed no significant changes. In experiment II, rats exhibited inhibited macrophage infiltration, which is associated with significantly impaired of wound healing. Conclusions: Our study suggests that induction chemotherapy, associated with leukopenia in the early phase of wound healing, increases the risk of bronchial anastomosis leakage. Postoperative macrophage depletion is one of the most important causes of impaired wound healing.     

Experimental Obstructive Jaundice Results in Oxidized Low-Density-Lipoprotein Accumulation in Surgical Wound of Rats

Introduction : Mounting evidence suggests that impaired wound healing is a well-defined consequence in obstructive jaundice and, as redox-regulated processes are relevant to wound healing, it is not unreasonable to suppose that oxidative stress associated with lipid peroxidation in cholestasis might be a systemic phenomenon probably comprising all tissues and organs, including wounds. The aim of the present investigation was to analyse the lipid peroxidation status of surgical wounds, in terms of oxidized low-density-lipoprotein (oxLDL) accumulation in experimental obstructive jaundice.

Methods : Sixteen Wistar-Albino rats weighing 200–230 gr were randomly divided into two groups. Group I (n = 8) was designed as the prolonged obstructive jaundice group and was subjected to bile duct ligation. Group II (Sham-control, n = 8) rats underwent laparotomy alone and bile duct was just dissected from the surrounding tissue. Histopathological evaluation, immunohistochemical screening and immunoflourescent staining of the surgical wound was conducted to the bile-duct ligated rats and control group on the 21^st postoperative day.

Results : Wound healing was found to be impaired in jaundiced rats histopathologically. When compared with the control group, significant positive oxLDL staining and intracellular accumulation of TNF-a, IL-2 and iL-6 was detected in the wound sections of the prolonged obstructive jaundice group.

Conclusion : Our present data is the first in the literature, indicating significant oxLDL accumulation in surgical wounds of cholestatic rats, which might be one of the results of systemic oxidative stress leading to deficient healing capacity as a consequence of persistent inflammation.     

The Effect of Erythropoietin on Anastomotic Healing of Irradiated Rats

ABSTRACT

Aim: The aim of the present study is to evaluate the possible protective effects of erythropoietin (EPO) on anastomotic wound healing after preoperative radiotherapy according to its pleiotropic mechanism of action. Methods: Thirty-two male Wistar albino rats were randomized into four groups containing eight rats each: ANAS group, standard resection plus anastomosis; RT+ANAS group, radiation plus standard resection plus anastomosis; ANAS+EPO group, standard resection plus anastomosis plus EPO; RT+ANAS+EPO, radiation plus standard resection plus anastomosis plus EPO. All animals were sacrificed by cardiac puncture, and anastomotic healing was measured by bursting pressure, hydroxyproline (OHP) levels, myeloperoxidase (MPO) activity and histopathological evaluations. Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) were also measured in serum specimens. Results: OHP levels in the RT+ANAS + EPO group were significantly increased compared with other groups (p < .05). In contrast, MPO activity in the RT+ANAS+EPO group was significantly decreased compared with other groups (p < .05). Serum MDA levels were found to be decreased in the ANAS+EPO and RT+ANAS+EPO groups (p < .05). Group comparisons demonstrated that bursting pressure was significantly higher in EPO treated rats (p < .05). The histopathology results revealed that EPO treatment improves anastomotic wound healing though decreased necrosis and inflammatory cell infiltration and increased fibroblast activity. Conclusion: The findings of the present study indicate that EPO contributes to wound healing and the strength of colon anastomosis following radiation due to its antioxidant and anti-inflammatory effects, but further studies are needed to explore the significance of these effects.     

Topical grape (Vitis vinifera) seed extract promotes repair of full thickness wound in rabbit

In recent years, oxidative stress and free radicals have been implicated in impaired wound healing. Grape (Vitis vinifera) seed extract (GSE) possesses anti-inflammatory and antioxidant properties. The present study was undertaken to assess the potential activity of grape seed hydroalcoholic extract in wound healing in rabbits. Rabbits of either sex were subjected to a 20 × 20 mm square excision made over the skin of the back. The animals were randomly divided into seven experimental groups, as negative and positive control, eucerin and treatments. Negative control group did not receive any treatment. Positive control and eucerin groups received phenytoin cream (1%) and topical eucerin, respectively, twice a day from the beginning of experiments to complete wound closure. Treatment groups were treated topically by cream of GSE (2, 5, 10 and 70% w/w) in eucerin base, twice daily. For evaluation of the percentage of wound healing, area of the wound was measured daily. Histological studies were performed on the 7th and 15th days of treatments. After complete healing, hydroxyproline content and tensile strength measurement of tissue samples were done. Results showed that there were statistically significant differences between GSE treatments groups and eucerin animals (P < 0·05) in most of the days. Rabbits treated with 2% GSE had best results (completed healing in 13 days, higher hydroxyproline content and higher tissue resistance). We concluded that the extract of 2% GSE administered topically has a good potential to promote wound healing in wound model of rabbits.     

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.     

恒磁场对SD大鼠深创面愈合的影响

目的：探讨恒磁场对SD大鼠深创面愈合的影响,恒磁场对创面愈合过程中VEGF表达的影响,以及不同强度恒磁场治疗SD大鼠深创面的区别。方法：将48只清洁级SD大鼠随机分成0．16T、0．32T磁疗组和对照组。分别在术后第3、6、9、12天每组处死4只大鼠,测定创面愈合指数,免疫组化检测肉芽组织VEGF表达。比较各组的创面愈合指数及VEGF表达情况。结果：④愈合指数。0．16T磁疗组在第6、9天时的愈合指数高于对照组,差异有统计学意义;0．32T磁疗组在第3、6、9、12天时的愈合指数高于对照组,差异有统计学意义。0.32T磁疗组与0．16T磁疗组相比差异无统计学意义。②创面修复不同时期VEGF表达观察结果。在术后第3、6天磁疗组VEGF表达强于对照组,差异有统计学意义;第9、12天磁疗组与对照组相比差异无统计学意义（P〉0．05）。0．32T磁疗组与0．16T磁疗组相比差异无统计学意义。两个磁疗组在第6天时VEGF阳性率达到整个愈合过程中的峰值,而对照组在第9天时才达到高峰,且VEGF表达强度低于两个磁疗组。结论：0．16T及0．32T恒磁片均能促进SD大鼠深创面的愈合,恒磁场促进深创面愈合的机制可能和在创面愈合早、中期增强VEGF的表达有关。     

Effects of glutamine on wound healing

Studies reporting the need for replacing amino acids such as glutamine (Gln), hydroxymethyl butyrate (HMB) and arginine (Arg) to accelerate wound healing are available in the literature. The primary objective of this study was to present the effects of Gln on tissue hydroxyproline (OHP) levels in wound healing. This study was conducted on 30 female Sprague Dawley rats with a mean weight of 230 ± 20 g. Secondary wounds were formed by excising 2 × 1 cm skin subcutaneous tissue on the back of the rats. The rats were divided into three equal groups. Group C (Control): the group received 1 ml/day isotonic solution by gastric gavage after secondary wound was formed. Group A (Abound): the group received 0·3 g/kg/day/ml Gln, 0·052 g/kg/day/ml HMB and 0·3 g/kg/day/ml Arg by gastric gavage after secondary wound was formed. Group R (Resource): the group received 0·3 g/kg/day/ml Gln by gastric gavage after secondary wound was formed. The OHP levels of the tissues obtained from the upper half region on the 8th day and the lower half region on the 21st day from the same rats in the groups were examined. Statistical analysis was performed using the statistics program SPSS version 17.0. No statistically significant differences were reported with regard to the OHP measurements on the 8th and 21st days (8th day: F = 0·068, P = 0·935 > 0·05; 21st day: F = 0·018, P = 0·983 > 0·05). The increase in mean OHP levels on the 8th and 21st days within each group was found to be statistically significant (F = 1146·34, P = 0·000 < 0·001). We conclude that in adults who eat healthy food, who do not have any factor that can affect wound healing negatively and who do not have large tissue loss at critical level, Gln, Arg and HMB support would not be required to accelerate secondary wound healing.