Pyramid environment reduces the wound healing suppressant properties of dexamethasone in albino rats

With a view to investigate the contribution and role of environment within a wooden pyramid model on the wound healing suppressant effect of dexamethasone in rats, wound breaking strength, dry weight, hydroxyproline content and histology of granulation tissue of the dead space wound were studied in rats. The results indicate that the environment within the wooden pyramid not only promotes significant wound healing but also reduces the wound healing suppressant effect of dexamethasone. Histological studies also confirmed the results.     

Effect of topical phenytoin on burn wound healing in rats

To evaluate the effect of phenytoin on burn wounds and to compare the effect of the combination of topical phenytoin preparation in dexamethasone treated burn wounds in rats, partial thickness thermal burn wounds were inflicted upon five groups of six rats each. Group I was assigned as control, Group II received the standard silver sulphadiazine, Group III was given topical phenytoin and Group IV received injection dexamethasone, Group V received the combination of the phenytoin and the dexamethasone. The parameters observed were epithelialization period, percentage of wound contraction and histopathological analysis as indicative of the process of healing. Phenytoin group showed significant improvement in burn wound contraction in comparison to standard silver sulphadiazine group, the combination group of topical phenytoin and dexamethasone also showed significant contraction compared to dexamethasone group. The period of epithelialization also decreased significantly in groups II, III and V. In conclusion, phenytoin promotes burn wound healing as evidenced by decrease in period of epithelialization and faster wound contraction.     

Effects of procoagulants on wound healing

As blood coagulation is a prelude for wound healing, a systemic haemocoagulant (Botropase) and local procoagulants (thrombin and fibrin) were evaluated on physical (wound breaking strength, wound half-closure time and period of epithelization), biochemical (granuloma-hydroxyproline and hexosamine) and histological attributes of healing wounds in albino rats. Botropase prompted all phases of tissue repair. Thrombin delayed wound contraction whereas fibrin had no discernable action. The findings that procoagulants modify healing process has bearing on their surgical use.     

Effect of Ocimum sanctum Linn. on normal and dexamethasone suppressed wound healing

Ethanolic extract of leaves of O. sanctum was investigated for normal wound healing and dexamethasone depressed healing using incision, excision and dead space wound models in albino rats. The extract of O. sanctum significantly increased the wound breaking strength in incision wound model. The extract treated wounds were found to epithelialize faster and the rate of wound contraction was significantly increased as compared to control wounds. Significant increase in wet and dry granulation tissue weight, granulation tissue breaking strength and hydroxyproline content in dead space wound model was observed. The extract significantly decreased the antihealing activities of dexamethasone in all the wound models. The results indicated that the leaf extract promotes wound healing significantly and able to overcome the wound healing suppressing action of dexamethasone. Histological examination of granulation tissue to determine the pattern of lay-down for collagen confirmed the results.     

Wound healing property of ethanolic extract of leaves of Hyptis suaveolens with supportive role of antioxidant enzymes

Ethanolic extract of leaves of Hyptis suaveolens was evaluated for its wound healing activity in ether-anaesthetized Wistar rats at two different doses (400 and 800 mg/kg) using incision, excision, and dead space wound model. Significant increase in skin breaking strength, granuloma breaking strength, wound contraction, hydroxyproline content and dry granuloma weight and decrease in epithelization period was observed. A supportive study made on granuloma tissue to estimate the levels of catalase and superoxide dismutase recorded a significant increase in the level of these antioxidant enzymes. Granuloma tissue was subjected to histopathological examination to determine the pattern of lay-down for collagen using Van Gieson and Masson Trichrome stains. Enhanced wound healing activity may be due to free radical scavenging action of the plant and enhanced level of antioxidant enzymes in granuloma tissue. Better collagenation may be because of improved antioxidant studies.     

Matrigel increases the rate of split wound healing and promotes keratinocyte `take' in deep wounds in rats

The influence of matrigel, a mixture of the components of thebasement membrane, on the wound healing was studied in a modelof experimental wounds in rats. Matrigel was found to increasethe rate of epithelization of split-thickness wounds. The modelof deep wound was developed in which the host animal could notprovide enough migrating and proliferating keratinocytes tocover the wound area. The model is relevant to severe burns andinjuries in humans. When rat keratinocyte suspension wastransplanted into deep wounds, cell retention in the wound bedwas only observed if matrigel was added together with the cells.Increasing matrigel concentration in the wound was seen toenhance the rate of wound area coverage by the cells. Althoughthe process of healing seemed macroscopically normal, afterhistological screening of the biopsies cell in the wouldappeared as amorphous aggregates and tubules rather thenstratified epidermis.     

枯草芽胞杆菌活菌制剂促进烧伤创面愈合的实验研究

目的　探讨枯草芽胞杆菌活菌制剂对烧伤创面愈合的影响。方法　通过大鼠深Ⅱ°烧伤模型,使用枯草芽胞杆菌活菌制剂,观察烧伤创面愈合过程中,成纤维细胞增殖周期的变化,以及测定羟脯氨酸（OHP）的含量,同时记录烧伤创面愈合时间,从而评价该制剂对烧伤创面愈合的影响。结果　应用枯草芽胞杆菌活菌制剂可促进成纤维细胞分裂、增殖,胶原含量提高,创面愈合时间明显缩短。结论　枯草芽胞杆菌活菌制剂具有促进烧伤创面愈合的作用。     

Pretreatment with phenobarbitone modifies suppressant effect of cyclosporine on wound healing

Cyclosporine has been reported to suppress the tensile strength of healing incision wound. Prednisolone, an inducer of hepatic microsomal enzymes, abolished the tensile strength suppressant effect of cyclosporine. Cyclosporine is metabolized by the hepatic cytochrome P-450 enzymes. Induction of microsomal enzymes with phenobarbitone was evaluated for its effect upon the wound healing suppressant effect of cyclosporine. Pretreatment of male rats with phenobarbitone (75 mg/kg/day, ip) for 3 days resulted in alleviating the tensile strength suppressant effect of cyclosporine (5 mg/kg/day, po for 10 days). Phenobarbitone, per se, did not affect the tensile strength. That phenobarbitone prevents cyclosporine induced nephrotoxicity without affecting the humoral immunosuppressant action of cyclosporine has recently been reported. The possibility of modulating microsomal enzymes with phenobarbitone offers another approach in preventing cyclosporine-associated toxicities during immunosuppression.     

Influence of sea buckthorn (Hippophae rhamnoides L.) flavone on dermal wound healing in rats

The present investigation was undertaken to determine the efficacy of topical administration of flavone of sea buckthorn (Hippophae rhamnoides L.) on cutaneous wound healing in rats. Four full-thickness excision wounds were created on the back of rat and 1.0% w/v flavone prepared in propylene glycol was applied topically. Control animals received the vehicle alone in an identical manner. The healing of the wound was assessed by the rate of wound contraction, period of epithelialization, hydroxyproline, hexosamine, antioxidants estimation and histopathology of the granulation tissue. The sea buckthorn flavone promoted the wound healing activity as indicated by improved rate of wound contraction, decreased time taken for epithelialization (16.3 days versus 24.8 days in controls) and significant increase in hydroxyproline (26.0%) and hexosamine (30.0%) content. These findings were also confirmed by histopathological examinations. In addition, it was observed that sea buckthorn flavone possesses potent antioxidant properties as evidenced by significant increase in reduced glutathione (55.0%), vitamin C (70.0%) and catalase (20.0%) activities in wound granulation tissue. The flavone treatment also resulted in significant decrease in lipid peroxide levels (39.0%). The results suggest that the sea buckthorn flavone promotes wound healing activity.     

Biological production of silver nanoparticles by soil isolated bacteria and preliminary study of their cytotoxicity and cutaneous wound healing efficiency in rat

Biosynthesis of AgNPs by 37 different bacterial soil isolates was done and confirmed through visible spectrophotometry. Fifteen isolates were identified and two of them with the highest ability of AgNPs production were used for Transmission Electron Microscopy (TEM) and X-ray diffraction (XRD) tests. MTT assay for both of the obtained AgNPs was run and after determination their IC_50s, two different toxic and nontoxic doses of each AgNPs solution were chosen for wound healing assay. Forty eight rats were divided into 6 groups; two were the controls, two were administrated by the toxic and two were administrated by the nontoxic doses of AgNPs produced by Bacillus cereus and Escherichia fergusonii. Administration of the nontoxic doses of AgNPs had better wound healing effect than both of the toxic ones. The control groups had less wound healing properties. In conclusion, biologically produced AgNPs in their nontoxic doses accelerated the collagen formation and the epithelization and decelerated the angiogenesis and duration of completion the epithelization.     

A therapeutic approach for diabetic wound healing using biotinylated GHK incorporated collagen matrices

Chronically elevated blood glucose levels result in reduced leukocyte function and cell malnutrition, which contribute to a high rate of wound infection and associated healing problems in diabetic patients. In the present study, the role of biotinylated GHK peptide (BioGHK) incorporated collagen biomaterial was tested for wound healing in diabetic rats. The rate of wound contraction and the levels of collagen, uronic acid, protein and DNA in the granulation tissue were determined. Further, the concentration of nitric oxide and other skin antioxidants was also monitored during the study. In diabetic rats treated with BioGHK incorporated collagen (Peptide Incorporated Collagen--PIC), the healing process was hastened with an increased rate of wound contraction. Glutathione (GSH) and ascorbic acid levels in the skin of streptozotocin-induced diabetic rats were higher in the PIC group as compared to control (Untreated) and collagen (Collagen Film--CF) treated groups. Superoxide dismutase (SOD) and catalase (CAT) activity was altered in all the groups. In vitro fibroblast cell culture studies suggest that PIC promotes fibroblast growth. Histological evaluation by haematoxylin-eosin and Masson's trichrome method revealed epithelialization, increased synthesis of collagen and activation of fibroblasts and mast cells in the PIC group. This study provides a rationale for the topical application of BioGHK incorporated collagen as a feasible and productive approach to support diabetic wound healing.     

Possibility of predicting rat wound epithelization by changes in matrix metalloproteinases activities in wound exudate

The engraftment of a free skin graft introduced into an unhealing wound as a source of epithelization in combination with a transplantation of a dermal equivalent was studied in rats. The course of wound healing was estimated by changes in the activity levels of metalloproteinases (MMPs) in wound exudates. It was shown that the results of skin-graft transplantation could be predicted by monitoring changes in wound exudates MMP-2 and MMP-9 activities. It was found that engraftment of the skin graft occurred at intermediate activity values of MMP-2 and MMP-9 in the wound exudates, whereas their low and high activities correspond to lysis of the transplanted skin graft.     

Scanning electron microscopical observations on epidermal wound healing in the PlanarianDugesia tigrina

Summary Epidermal wound healing in regeneratingDugesia tigrina (Planaria) has been studied using scanning electron microscopy (SEM). The normal epidermal surface and its differentiations have been descrebed. Observations on living material reveal the highly dynamic state of the wound in invididual animals and its more or less continously changing size due to the state of activity of the animals. These observations show good agreement with the SEM studies, which allow a clear delineation of cellular details of the wound, the wound margins and the apposing epidermal regions. These details are described. The over-all picture of planarian wound healing that emerges is briefly as follows: Epithelization is characterized by absence of proliferation from the old intact epidermis. Variable contraction of smooth muscle cells reduces the wound size to a certain extent. Simultaneously with this and also during a longer period epidermal cells adjacent to the wound are extending and some become highly attenuated. These two processes together are only to a certain degree effective in wound closure because of a definite epidermal cell deficit which is reflected in the emergence of an epidermal wound edge reflecting the maximal contribution of these two processes to an attempt to close the wound. Complete epithelization is effected by the operation of a third mechanism: Recruitment of cell through flow of subjacent blastemal cells (including rhabdite-forming cells) along the wound border; these cells subsequently occupy a peripheral position in the wound. This process is supplemented by cell immigration and insertion into the adjacent old epidermis and in the wound cell sheet. Rhabdite-forming cells contribute predominantly to this process. Eventually integration between old epidermal cells and the newly recruited cells which differentiate into epidermal cells results in final epithelization. Complete wound healing is based on interactions between the epidermal cell system and the regenerating subepidermal membrane-connective tissue filament-muscle cell system.     

The antagonism of glucocorticoid inhibition of wound healing in rats by growth hormone-releasing factor

Daily therapeutic injections of cortisone to rats will cause weight loss and impaired wound healing. Weight loss is attributed to the catabolic effect of steroid, whereas impaired healing is associated with reductions in fibroplasia and connective tissue deposition. As the major structural protein component of connective tissue is collagen, its absence is responsible for the retarded gain in wound breaking strength. Cortisone also blocks wound closure by inhibiting wound contraction. An anabolic agent such as growth hormone may antagonize the effect of cortisone on the wound healing process. Endogenous GH can be released from the pituitary by exogenous injections of growth hormone-releasing factor (GRF). Two synthetic GRF peptides, a natural 44-amino acid peptide of the human GRF sequence, GRF-44, and an N-terminally substituted analog 29 residues, GRF-29A, were studied. Each was given twice daily with a single daily injection of cortisone for a 7-day period. Concurrent administration of GRF-44 or GRF-29A and cortisone to rats had no effect on restored body weight loss or inhibited wound contraction. While GRF-44 restored collagen deposition and caused restored wound breaking strength, GRF-29A was ineffective in restoring either. GRF-44, a synthetic peptide that stimulates pituitary release of growth hormone, antagonized some of the inhibiting effect of steroid on wound repair by promoting fibroplasia and collagen deposition.     

The effect of finger millet feeding on the early responses during the process of wound healing in diabetic rats

In the present study, the role of finger millet feeding on skin antioxidant status, nerve growth factor (NGF) production and wound healing parameters in healing impaired early diabetic rats is reported. Hyperglycemic rats received food containing 50 g/100 g finger millet (FM). Non-diabetic controls and diabetic controls received balanced nutritive diet. Full-thickness excision skin wounds were made after 2 weeks prior feeding of finger millet diet. The rate of wound contraction, and the levels of collagen, hexosamine and uronic acid in the granulation tissue were determined. The skin antioxidant status and lipid peroxide concentration were also monitored during the study. In hyperglycemic rats fed with finger millet diet, the healing process was hastened with an increased rate of wound contraction. Skin levels of glutathione (GSH), ascorbic acid and alpha-tocopherol in alloxan-induced diabetic rat were lower as compared to non-diabetics. Altered activities of superoxide dismutase (SOD) and catalase (CAT) were also recorded in diabetics. Interestingly, thiobarbituric acid reactive substances (TBARS) were elevated in the wound tissues of all the groups, when compared to normal (unwounded) skin tissues. However, in diabetic rats the TBARS levels of both normal and wounded skin tissues were significantly elevated (P < 0.001) when compared with control (non-diabetic) and diabetics fed with FM. Impaired production of NGF, determined by ELISA, in diabetic rats was improved upon FM feeding and further confirmed by immunocytochemical observations reflects the increased expression of NGF in hyperglycemic rats supplemented with FM-enriched diet. Histological and electron microscopical evaluations revealed the epithelialization, increased synthesis of collagen, activation of fibroblasts and mast cells in FM-fed animals. Thus, increased levels of oxidative stress markers accompanied by decreased levels of antioxidants play a vital role in delaying wound healing in diabetic rats. However, FM feeding to the diabetic animals, for 4 weeks, controlled the glucose levels and improved the antioxidant status, which hastened the dermal wound healing process.     

The effect of nerve growth factor on the early responses during the process of wound healing

In this study, we investigated the role of nerve growth factor (NGF)-incorporated collagen on wound healing in rats. Full-thickness excision wounds were made on the back of female rats weighing about 150-160 g. Topical application of NGF-incorporated collagen, at a concentration of 1 microg/1.2 mg collagen/cm(2), once a day, for 10 days resulted in complete healing of wounds on the 15th day. The concentrations of collagen, hexosamine and uronic acid in the granulation tissue were determined. The NGF-incorporated collagen-treated rats required shorter duration for the healing with an increased rate of wound contraction. Histological and electron microscopical evaluations were also performed, which reveal the activation of fibroblasts and endoplasmic reticulum and therefore increased level of collagen synthesis due to NGF application. These results clearly indicate that the topical application of NGF-incorporated collagen enhanced the rate of healing of excision wounds.     

In vivo effect of whole grain flour of finger millet (Eleusine coracana) and kodo millet (Paspalum scrobiculatum) on rat dermal wound healing

Influence of finger millet and kodo millet on rat dermal wound healing was assessed by making a 4 cm2 (2 x 2 cm) excision wound on the shaven back of rats under ether anesthesia. Finger millet or kodo millet flour (300 mg) as aqueous paste was applied topically once daily for 16 days. The granulation tissue formed on day 4, 8 and 12 was used to estimate some biochemical parameters like protein, DNA, collagen and lipid peroxides. There was significant increase in protein and collagen contents and decrease in lipid peroxides. Biophysical parameters like rate of contraction and number of days for epithelialization were also studied. Rate of contraction was 88-90% in kodo millet and finger millet treated rats in comparison to 75% in untreated rats. The number of days for complete closure of wounds was lower for finger millet (13 days) and kodo millet (14 days) treated rats in comparison to untreated (16 days) rats. The results implicate a possible therapeutical role for finger millet and kodo millet in accelerating the process of wound healing.     

創傷癒合和組織再生的研究——Ⅰ.白鼠皮膚切除創傷癒合過程中創口的收縮

一.引言在高等動物的皮膚創傷癒合過程中,創口的收縮是很顯著的現象,使它所形成的疤痕往往小於當初創傷的部分。因此,創口的收縮作用,對於創傷癒合來說,是具有極大意義的。最早Carrel(1910)在研究狗的皮膚創傷癒合工作中,即已指出這個創口收縮的重要性;並且提出是由於肉芽的收縮作用(granulous retrac-     

The use of morphometric and fractal parameters to assess the effects of 5-fluorouracil, interferon and dexamethasone treatment on colonic anastomosis healing: an experimental study in rats

Adjuvant chemotherapy and steroid therapy have been demonstrated to interfere with the wound healing process. The aim of this study was to evaluate the effects of 5-fluorouracil, interferon, and dexamethasone, on the healing of colon anastomosis by assessing morphometric and fractal parameters of the colonic wall. An experimental anastomosis of the ascending colon was performed in 60 male Wistar rats, which were then randomly assigned to four groups. On the second to sixth post-operative days, the rats were administered 5-fluorouracil, interferon-α, dexamethasone, or 0.9% NaCl solution as a control. Macroscopic, histomorphometric and microbiological evaluation was performed in order to assess healing of the anastomosis. In three animals from the dexamethasone group, there was leakage of anastomosis; adhesion formation was highest in the interferon group, and significantly higher than in the control and 5-fluorouracil groups. Histomorphometric parameter alterations were most pronounced on the seventh and fourteenth post-operative days in all treatment groups, with submucosal thickness the most affected parameter. Connective tissue fractal dimension was significantly decreased in those animals treated with interferon and dexamethasone. All three pharmaceutical agents impaired healing of anastomosis, and promoted infection in the anastomosis and skin wound sites. As dexamethasone induced both morphometric and macroscopic alterations, it was considered the most detrimental in this study.     

Wound healing potential of ethanolic extract of Kalanchoe pinnata Lam. leaf--a preliminary study

The extract of K. pinnata was evaluated for its wound healing activity by using excision wound model in rats. On day 11, animals treated with the ethanolic leaf extract exhibited 86.33% reduction in the wound area, compared to petroleum jelly treated control (69.36%) and the mupirocin treated standard (85.49%). The hydroxyproline content of extract treated animals was higher, as compared to control and the standard groups. Histological analysis was also consistent with the proposal that K. pinnata leaf extract exhibits significant wound healing potential. The increased rate of wound contraction and hydroxyproline content in the extract treated animals supports the claims made by traditional healers of the benefits obtained from the medicinal use of K. pinnata.