Effectiveness of topical zinc oxide application on hypertrophic scar development in rabbits.

BACKGROUND: The etiology, biology, prevention and effective treatment of hypertrophic scars have not exactly been defined. Topical zinc oxide application was shown to be effective in the treatment of proliferative scars. We studied the effectiveness of topical zinc oxide ointment in the prevention of hypertrophic scar development by using the rabbit ear hypertrophic scar model. METHODS: Circular full-thickness skin excisions were performed on both ears of 10 rabbits. The rabbits were divided into two groups and topical 40% zinc oxide ointment was applied daily to one ear and the ointment base was applied as placebo to the other ear. Scar samples were taken in the 3rd week in group 1 and in the 6th week in group 2. All of the specimens were divided into two halves: one half for histopathologic/histomorphometric examinations and the other half for biochemical studies. RESULTS: Application of topical zinc oxide ointment decreased clinical scar hypertrophy scores significantly (p=0.017) at 6th week in comparison with placebo. Topical zinc oxide also reduced nodule formation histopathologically at 6th week in comparison with placebo but this was not significant statistically (p>0.05). CONCLUSION: The findings of this study may have clinical implications on the management of human hypertrophic scars.

The effects of local and sustained release of fibroblast growth factor on wound healing in esophageal anastomoses.

BACKGROUND/PURPOSE: Postsurgical complications, such as anastomotic leaks in patients with esophageal atresia, have remained unchanged during the last 3 decades. Growth factors enhance healing in several wound-healing models. Therefore, an experimental study was used to evaluate the effects of local and sustained release of basic fibroblast growth factor (FGF) on wound healing in esophageal anastomoses. MATERIALS AND METHODS: Twenty-four male Wistar albino rats, which were subjected to a 1-cm segmental resection of the abdominal esophagus followed by end-to-end anastomosis, were allocated into 3 groups. Group I, the control group, had no gelatin film applied to the anastomosis. In group II (gelatin film without FGF) and group III (gelatin film with FGF), anastomoses were covered with unloaded and 2.55 mug FGF-loaded gelatin films, respectively. On postoperative day 7, bursting pressures, histopathologic collagen deposition, and tissue hydroxyproline concentrations of the anastomoses were then analyzed and compared. RESULTS: Mean bursting pressures, mean submucosal and muscular collagen deposition scores, and mean tissue hydroxyproline concentrations differed significantly between groups. Mean bursting pressures were 22.5 +/- 3.1 mm Hg in group I, 29 +/- 1.6 mm Hg in group II, and 63.2 +/- 6.8 mm Hg in group III (P < .001). Mean submucosal collagen deposition scores (group I: 0.7 +/- 0.2, group II: 0.7 +/- 0.1, group III: 1.5 +/- 0.2; P = .02) and mean muscular collagen deposition scores (group I: 0.8 +/- 0.2, group II: 0.8 +/- 0.1, group III: 1.8 +/- 0.1; P = .01) were significantly higher in FGF animals than the other in the other 2 groups. Mean tissue hydroxyproline concentrations were 2.4 +/- 0.5 microg/mg in group I, 3.9 +/- 0.4 microg/mg in group II, and 6.0 +/- 1.0 microg/mg in group III (P = .007). CONCLUSION: Local and sustained release of FGF enhanced wound healing in esophageal anastomoses in this animal model.

Superoxide dismutase activity in gingiva in type-2 diabetes mellitus patients with chronic periodontitis.

OBJECTIVE: Antioxidant defence reduces in diabetes mellitus (DM) and periodontitis. This study investigates antioxidant enzyme; superoxide dismutase (SOD) activity in gingiva and blood glucose and lipid levels in type-2 DM patients and systemically healthy individuals with chronic periodontitis (CP). MATERIALS AND METHODS: Periodontal parameters, blood glycated-haemoglobin (HbA1c), glucose and lipid levels, and gingival-SOD activities (spectrophotometric assay) were measured in 17 DM patients with CP (DMCP), 17 systemically healthy CP patients, 18 periodontally healthy DM patients (DMPH), and 17 healthy controls (PH). RESULTS: Periodontal parameters were higher in periodontitis groups than the controls (p<0.05), while there was no difference between the periodontitis groups and between the control groups. HbA1c, glucose, and triglyceride levels were higher in diabetic groups than the non-diabetic groups (p<0.05). Low-density lipoprotein (LDL), very-LDL and cholesterol values of the DMCP group did not significantly differ from the CP group. No differences existed between diabetic patients with and without periodontitis in HbA1c, glucose, and lipid levels and the same was true for non-diabetic patients with and without periodontitis. Gingival-SOD activity was lower in periodontitis groups than the matched control groups (p<0.05). DMPH group had the highest and CP group had the lowest SOD levels. There were correlations between periodontal parameters, gingival-SOD activity, HbA1c, glucose and high-density lipoprotein (HDL) levels. CONCLUSION: The results suggest that gingival-SOD activity increases in diabetes and decreases in periodontitis and relations may exist between gingival-SOD activity, periodontal status, HbA1c, glucose and HDL levels. The higher gingival-SOD activity in diabetes may be attributed to an adaptive mechanism in the tissue.

Cod liver oil supplementation improves cardiovascular and metabolic abnormalities in streptozotocin diabetic rats.

Abnormalities in the metabolism of essential fatty acids and the results of increased oxidative stress have been implicated in cardiovascular disorders observed in diabetes mellitus. This study, therefore, aimed to investigate the effects of cod liver oil (CLO, Lysi Ltd, Iceland), which comprises mainly an antioxidant vitamin A, n:3 polyunsaturated fatty acids (n:3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cardiovascular abnormalities in streptozotocin (STZ)-diabetic rats. Two days after single STZ (55 mg kg(-1), i.p.) or vehicle injection, diabetes was verified by increased blood glucose, and non-diabetic and diabetic rats were left untreated or treated with CLO (0.5 mL kg(-1) daily, by intragastric probing) for 12 weeks. Plasma glucose, triacylglycerol and cholesterol concentrations were significantly elevated in 12-week untreated-diabetic rats; CLO provided better weight gain, entirely prevented the plasma lipid abnormalities, but partially controlled the glycaemia in diabetic rats. In isolated aorta rings, diabetes resulted in increased phenylephrine-induced vasoconstriction and isoprenaline-induced vasorelaxation, impaired endothelium-dependent vasodilatation and unchanged responsiveness to sodium nitroprusside. CLO treatment completely prevented endothelial deficiency, partly corrected the phenylephrine-induced vasoconstriction and did not affect the responses to isoprenaline and sodium nitroprusside in diabetic aorta. Diabetes also produced a marked decrease in the rate of spontaneously beating right atria and a significant increase in basal contractile force of left ventricular papillary muscle. The responsiveness of right atria to the positive chronotropic effect of isoprenaline was significantly decreased in diabetic rats, and was increased in CLO-treated diabetic rats. The positive chronotropic effect of noradrenaline was markedly increased in diabetic atria, but prevented by CLO treatment. Diabetes also resulted in an increased positive inotropic response of papillary muscle to both noradrenaline and isoprenaline, which were prevented by CLO treatment. CLO treatment also resulted in lower tissue sensitivity (pD(2)) to these agonists in diabetic papillary muscle. Ventricular hydroxyproline content was found to be unchanged among the experimental groups. The ultrastructure of diabetic myocardium displayed various degenerations (i.e. intracellular oedema, myofibrillar fragmentation, condensed pleomorphic mitochondria, thick capillary irregular basement membrane, swollen endothelial cells), which were partially prevented by CLO treatment. We conclude that the supplementation with CLO is effective in preventing cardiovascular disorders observed in experimental diabetes.

The effect of erythropoietin on healing of obstructive vs nonobstructive left colonic anastomosis: an experimental study.

BACKGROUND: Anastomotic leakage is an important problem following primary resection in the left colon and is even more prominent when obstruction is present. We aimed to evaluate the possible effects of erythropoietin on the healing of anastomosis under both obstructive and non-obstructive states. METHODS: Forty male Wistar albino rats were divided into four groups. In group I, two cm left colonic resection and primary anastomosis were done. In group II, left colon were completely ligated and 24 hours later animals were re-operated for segmental resection. The same procedures were performed for rats in group III and IV in respect to group I and II and, 500 IU/kg a day erythropoietin were given in the latter two groups for seven days. For the quantative description of anastomotic healing mechanical, biochemical and histopathological parameters were employed on the seventh day and the animals were sacrificied. RESULTS: Although erythropoietin had positive effects on bursting pressure in group IV when compared to group II, it has no effect in group III. Despite the increased tissue hydroxyproline levels in group IV, erythropoietin failed to show any effects in group III. Erythropoietin had positive effects on neovascularization, fibroblast proliferiation and storage of collagen in group IV. CONCLUSION: We failed to find any direct and evident effects of erythropoietin on healing of left colonic anastomosis. On the other hand, erythropoietin might prevent negative effects of obstruction on healing.

Methylene blue prevents surgery-induced peritoneal adhesions but impairs the early phase of anastomotic wound healing.

OBJECTIVES: Adhesion formation continues to be an important problem in gastrointestinal surgery. In recent years, methylene blue (MB) has been reported to be an effective agent for preventing peritoneal adhesions. However, its effects on the wound healing process are unknown. In the present study, we investigated the effects of MB on the early and late phases of anastomotic wound healing and on adhesion formation. METHODS: We randomly categorized 92 rats into 2 groups in bursting pressure measurements and 50 rats into 3 groups in the adhesion model. We divided the animals into saline-treated (n = 46) or MB-treated (n = 46) groups. Bursting pressures of the anastomoses were measured on postoperative days 3 and 7. In biochemical studies, tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity were measured on postoperative days 3 and 7. In the adhesion model, we randomly categorized rats into sham (n = 10), saline-treated (n = 20) and MB-treated (n = 20) groups, and the formation of intraperitoneal adhesions was scored on postoperative day 14. We compared the measurement of bursting pressure and biochemical measurements of tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity. Histopathological findings of specimens were presented. RESULTS: During the early phase of wound healing (postoperative day 3), bursting pressures, tissue hydroxyproline, total nitrite/nitrate levels and nitric oxide synthase activity in the MB-treated group were significantly lower than those of the saline-treated group. On postoperative day 7, there was no significant difference in these parameters between MB and saline-treated groups. In the adhesion model, MB caused a significant reduction in the formation of peritoneal adhesions. CONCLUSION: MB prevents peritoneal adhesions but causes a significant impairment of anastomotic bursting pressure during the early phase of the wound healing process by its transient inhibitory effect on the nitric oxide pathway.

Local granulocyte-macrophage colony-stimulating factor improves incisional wound healing in adriamycin-treated rats.

PURPOSE: Neoadjuvant treatment is often given for locally advanced malignancies; however, clinical and experimental studies have shown that some chemotherapeutic agents impair wound healing. It has been reported that granulocyte-macrophage colony-stimulating factor (GM-CSF) applied locally improves dermal wound healing. Thus, we investigated the effects of locally injected GM-CSF on abdominal wounds impaired by adriamycin, a widely used chemotherapeutic agent. METHODS: We divided 120 female Sprague-Dawley rats into five treatment groups of 24 rats. Group 1 received saline 8 mg/kg intravenously (i.v.) + laparotomy 14 days later (control); group 2 received 8 mg/kg i.v. adriamycin + laparotomy 14 days later; group 3 received adriamycin 8 mg/kg i.v. + laparotomy + local GM-CSF 50 microg 14 days later; group 4 received saline 8 mg/kg i.v. + laparotomy + local GM-CSF 50 microg 14 days later; and group 5 received adriamycin 8 mg/kg i.v. + laparotomy + systemic GM-CSF 50 microg 14 days later. Sutures were removed on postoperative day (POD) 7 in all five groups, and the abdominal bursting pressures were measured and recorded. Tissue samples were taken from the incision line for histopathological evaluation and hydroxyproline content measurement. RESULTS: The bursting pressure was significantly lower in groups 2 and 5 than in groups 1, 3, and 4. The hydroxyproline content and histopathological findings supported this result. CONCLUSION: The local injection of GM-CSF improved impaired wound healing in adriamycin-treated rats.

[Does sepsis impair the healing of colonic anastomosis in splenectomized rats?]. / Splenektomi yapilan siçanlarda sepsis kolon anastomozunun iyilesmesini olumsuz etkiler mi?

BACKGROUND: To investigate the effect of splenectomy on the healing of colonic anastomoses under normal and septic conditions. METHODS: Forty Wistar rats were assigned into six groups: group 1: sham, group 2: colonic anastomose, group 3: splenectomy, group 4: colonic anastomose plus sepsis, group 5: colonic anastomose plus splenectomy, group 6: colonic anastomose plus splenectomy plus sepsis. The rats underwent a standardized left colonic resection and primary anastomosis and/or splenectomy. Sepsis was produced by cecal ligation and puncture. Wound healing was evaluated by bursting pressure and hydroxiproline estimates. RESULTS: Bursting pressures were as follows: group 1: 173 +/- 14 mmHg, group 2: 186 +/- 7 mmHg, group 3: 168 +/- 6 mmHg, group 4: 113 +/- 14 mmHg, group 5: 167 +/- 10 mmHg, and group 6: 183 +/- 3 mmHg. Hidroksiprolin contents were: group 1: 3.5 +/- 0.2 microg/mg, group 2: 3.2 +/- 0.3 microg/mg, group 3: 3.4 +/- 0.2 microg/mg, group 4: 2.3 +/- 0.2 microg/mg, group 5: 3.0 +/- 0.2 microg/mg, grup 6 3.2 +/- 0.1 microg/mg. Statistical significance was found between group 4 and the other groups (p<0.05). CONCLUSION: Sepsis impairs the healing of colonic anastomoses. However, sepsis does not impair the intestinal wound healing in splenectomized rats.

Granulocyte macrophage-colony stimulating factor improves impaired anastomotic wound healing in rats treated with intraperitoneal mitomycin-C.

PURPOSE: Intraperitoneal chemotherapy (IPCT) delivers higher local concentrations of cytotoxic drugs than intravenous (i.v.) chemotherapy, but it can adversely affect the healing of intestinal anastomoses if given in the early postoperative period. Intestinal anastomotic leakage is a serious surgical complication. Experimental and clinical studies have shown that the local administration of granulocyte macrophage-colony stimulating factor (GM-CSF) improves would healing. Therefore, we evaluated the effects of locally applied GM-CSF on anastomotic wound healing in rats treated with intraperitoneal mitomycin-C immediately after surgery. METHODS: We performed colon anastomoses in albino rats, which were then divided into three treatment groups. Group A was a control group that received no treatment, Group B was given intraperitoneal mitomycin-C postoperatively, and Group C was given intraperitoneal mitomycin-C with a local injection of GM-CSF postoperatively. We measured bursting pressures and hydroxyproline content, and histologically examined the resected anastomoses on postoperative day (POD) 3. RESULTS: Anastomotic healing was impaired after intraperitoneal mitomycin-C, but this was overcome by the injection of GM-CSF into the perianastomotic area. CONCLUSION: Local GM-CSF administration counteracts the detrimental effects of intraperitoneal mitomycin-C treatment on intestinal anastomoses in rats.

Analysis of superoxide dismutase activity levels in gingiva and gingival crevicular fluid in patients with chronic periodontitis and periodontally healthy controls.

OBJECTIVES: Superoxide dismutase (SOD) is an antioxidant enzyme that acts against superoxide, an oxygen radical, released in inflammatory pathways and causes connective tissue breakdown. In this study, SOD activities in gingiva and gingival crevicular fluid (GCF) from patients with chronic periodontitis (CP) and periodontally healthy controls were compared. MATERIAL AND METHODS: Twenty-six CP patients and 18 controls were studied. In patients, teeth with moderate-to-severe periodontal breakdown and > or =5 mm pockets that required full-thickness flap surgery in the right or left maxillary quadrant, and in controls, teeth scheduled for extraction for orthodontic reasons were studied. After the clinical measurements (probing depth, clinical attachment level, gingival index, gingival bleeding index, plaque index), GCF samples were collected. Tissue samples were harvested from the same teeth, during flap operation in patients and immediately after tooth extraction in controls. SOD activities were spectrophotometrically assayed. The results were statistically analysed. RESULTS: Gingival SOD activity was significantly higher in the CP group than in controls (p<0.05). No significant difference was found in GCF SOD activity between the groups (p>0.05). Correlations between gingival and GCF SOD activities were not statistically significant in CP and control groups (p>0.05). CONCLUSION: In CP, SOD activity seems to increase in gingiva, probably as a result of a higher need for SOD activity and protection in gingiva in CP than in periodontal health, while not significantly changing in GCF, suggesting a weak SOD activity in GCF in periodontal disease state. The weak correlation between gingival and GCF SOD activities suggests distinct actions of these SODs.

A novel approach for preventing esophageal stricture formation: sphingosylphosphorylcholine-enhanced tissue remodeling.

Using a new class of intracellular 2nd messengers to prevent stricture formation after caustic ingestion, sphingosylphosphorylcholine (SPC) has a wide spectrum of activity in cell growth regulation and signal transduction. Caustic esophageal burns were created with 15% NaOH in an experimental rat model. Control group animals (n = 10) had esophageal burns with no treatment, whereas the SPC group (n = 10) had esophageal burns gavaged with SPC for 7 days. Efficacy of treatment was assessed in 28 days by contrast esophagograms, histopathologic evaluation, and biochemically by tissue hydroxyproline (OHP) content. Contrast esophagograms demonstrated that SPC significantly prevented stricture formation. Obvious collagen deposition was present in submucosa, muscularis mucosa, and muscular layers in the control group compared with the SPC group. The damage to the esophageal wall on histopathologic examination was significantly lower in the SPC group (p < 0.05). Tissue OHP contents were significantly lower in the SPC-treated group (3.0 +/- 0.1 microg/mg) compared with the control group (4.3 +/- 0.2 microg/mg) (p < 0.05). We conclude that SPC improves healing following caustic esophageal burns. Furthermore, SPC is effective in preventing caustic esophageal strictures. These effects of SPC occur through its proliferative and specifically its remodeling effects on wound healing.

Sustained local application of low-dose epidermal growth factor on steroid-inhibited colonic wound healing.

BACKGROUND/PURPOSE: The effects of locally administered low-dose epidermal growth factor in a steroid-inhibited wound healing were investigated in a rat model. METHODS: Long-acting release of epidermal growth factor was enabled using microspheres embedded in gelatin sponge. Study groups consisted of 60 rats with 10 in each: colonic anastomosis only (C), plus pure gelatin sponge (CG), plus epidermal growth factor loaded sponge (CE), colonic anastomosis and steroid (S), plus gelatine sponge (SG), and plus epidermal growth factor-loaded gelatine sponge (SE) groups. Bursting pressure and wound hydroxy-proline content were measured. Bursting sites were recorded. Collagen deposits, inflammation, and foreign body reactions were evaluated. RESULTS: Bursting pressure and hydroxy-proline contents were found lowest in the S and highest in the CE groups (P <.01). There was almost no difference between C and SE groups. Bursts were encountered in peri-anastomotic normal colon sites in the nonsteroid-treated C, CG, and CE groups. They were noted overwhelmingly at the anastomosis in steroid-inhibited S, SG, and SE groups. Histopathology results showed a standstill at the inflammatory phase of healing in S and SG groups. The best healing was observed in the CE group. Degree of collagen accumulation was well correlated with bursting pressure and hydroxy-proline content data with a negligible foreign body reaction to gelatine sponge. CONCLUSIONS: Continuous local epidermal growth factor administration by microspheres in gelatin increases wound collagen and further enhances healing in colonic anastomoses even with steroid inhibition.

The role of the spleen on colonic anastomotic healing.

The role of the spleen on wound healing remains unclear. This study investigates the effect of splenectomy on the healing of colonic anastomoses. Twenty-six Wistar rats were assigned into four groups: sham, splenectomy, anastomoses, and splenectomy and anastomoses. The rats underwent a standardized left colonic resection and primary anastomoses, and/or splenectomy. Bursting pressure and hydroxyproline content were used to evaluate anastomotic healing, five days postoperatively. No differences were found in the bursting pressure and hydroxyproline content between the groups. The present results indicate that splenectomy has no negative effect on the healing of colonic anastomoses in rats.

Lipid peroxidation and extracellular matrix in normal and cirrhotic rat livers following 70% hepatectomy.

BACKGROUND/AIMS: The aim was to measure the deposition of collagens and proteoglycans and the underlying mechanism leading to lipid peroxidation due to oxidative stress in partially hepatectomized normal and cirrhotic rats. METHODOLOGY: Four groups of adult Wistar rats were used comprising normal livers, regenerated normal livers, cirrhotic livers, and regenerated cirrhotic livers. Cirrhosis was induced by intragastric administration of carbon tetrachloride and phenobarbital in the drinking water of the rats. Hydroxyproline, as a constituent of collagens, uronic acid, as a constituent of proteoglycans, and malondealdehyde, an end-product of lipid peroxides, were measured in normal and cirrhotic rats, and following partial hepatectomy. RESULTS: Hydroxyproline, uronic acid and malondealdehyde levels were 234.2 +/- 41.2, 11.82 +/- 1.92, 46.3 +/- 5.8 and 211.8 +/- 43.6, 9.16 +/- 1.41, 48.5 +/- 7.5 for normal and regenerated normal livers respectively. The values after partial hepatectomy in cirrhotic and regenerated cirrhotic livers were 396.9 +/- 48.5, 17.96 +/- 1.62, 144.5 +/- 25.1 and 309.6 +/- 43.2, 13.35 +/- 1.72, 229.9 +/- 24.4, respectively. When the cirrhotic liver group was compared with the normal liver group, the levels of hydroxyproline, uronic acid and malondealdehyde were significantly higher (p < 0.001). Uronic acid levels of regenerated normal and regenerated cirrhotic livers and hydroxyproline level of regenerated cirrhotic liver were significantly less than those of their non-regenerated states (p < 0.01). Although the malondealdehyde levels of normal and regenerated normal livers did not differ significantly (p > 0.05), the malondealdehyde levels of regenerated cirrhotic liver was significantly higher than cirrhotic liver (p < 0.01). The histopathological examination with light microscopy did not reveal any obvious difference between the groups other than between normal and cirrhotic. CONCLUSIONS: Cirrhotic livers revealed a significantly higher amount of extracellular matrix constituents and lipid peroxidation than normal livers. Although partial hepatectomy in cirrhotic livers caused decreases in the tissue levels of collagens and proteoglycans, it did not actually lower the ongoing oxidative stress, known as physiological lipid peroxidation, in normal and cirrhotic livers following partial hepatectomy.

Effect of electromagnetic fields and early postoperative 5-fluorouracil on the healing of colonic anastomoses.

BACKGROUND AND AIMS: Studies have indicated a deleterious effect of perioperative 5-fluorouracil (5-FU) administration on the healing of intestinal anastomoses. This study examined the effect of early postoperative 5-FU on the healing of colonic anastomoses and investigated the effect of electromagnetic fields (EMF) on colonic anastomotic repair under normal physiological conditions and in the presence of 5-FU therapy in a rat model. MATERIALS AND METHODS: Forty male Wistar rats were randomly assigned into four groups and underwent a standardized left colonic resection and anastomoses. The animals then served as control or received intraperitoneal 5-FU (20 mg/kg per day, 5 days), EMF stimulation (10.76 mT, 50 Hz; 2-h on/10-h off cycles, 7 days) or both, starting on the day of surgery. After 7 days anastomotic healing was assessed by measurement of hydroxyproline content and breaking strength. RESULTS: Hydroxyproline content increased in EMF exposed group (1.53+/-0.11 to 1.92+/-0.11 microg/mg) and in EMF + 5-FU group (1.53+/-0.11 to 1.89+/-0.12 microg/mg). Breaking strength also increased in the EMF group (0.23+/-0.02 to 0.27+/-0.01 MPa) and in the EMF + 5-FU group (0.23+/-0.02 to 0.28+/-0.01 MPa. No differences were found in hydroxyproline content or breaking strength between the 5-FU group and controls. CONCLUSION: Early postoperative 5-FU administration did not impair the healing of colonic anastomoses in rats. Additionally, EMF stimulation provided a significant gain in colonic anastomotic strength, in rat intestines in control animals and in animals exposed to 5-FU.

Locally applied granulocyte-macrophage colony-stimulating factor improves the impaired bowel anastomoses in rats with long-term corticosteroid treatment.

Inflammation is an essential component of the first phase of anastomotic wound healing, and it is suppressed by corticosteroids. The anti-inflammatory effect of corticosteroids is largely responsible for the impairment of wound healing in bowel anastomosis. It has been reported that local application of granulocyte-macrophage colony-stimulating factor (GM-CSF) improves the healing process in dermal wounds. In the present study, we investigated the effects of locally injected GM-CSF on anastomotic wound healing in long-term corticosteroid treated rats. Eighty male Sprague-Dawley rats were randomized into four groups. (1) control, (2) steroid, (3) steroid + local GM-CSF, (4) steroid + systemic GM-CSF. In groups 2, 3, and 4, methylprednisolone (5 mg/kg) was injected IM daily for 14 days. After 14 days, following anesthesia and laparotomy, colonic anastomosis was performed 3 cm away from the peritoneal reflection. In group 3, 50 mg GM-CSF was injected into the perianastomotic area. In group 4, 50 mg GM-CSF was applied subcutaneously. On postoperative day 3, repeat laparotomies were performed and bursting pressures, hydroxyproline levels, and histopathology examinations were studied. The mean values of bursting pressures and hydroxyproline levels in group 3, treated with steroid + local GM-CSF, were significantly higher than that of the group 2 and group 4 values. In the histopathology examination, the mean score of group 3 was significantly higher than that of groups 2 and 4. Our study indicates that local application of GM-CSF significantly improves the impaired anastomotic wound healing in rats treated with long-term corticosteroid.

Effects of portal triad occlusion on left-sided colonic anastomosis.

Anastomotic healing can deteriorate because of different local and systemic effects in cases of concomitant left colon and liver injuries. We evaluated the effects of portal triad occlusion (PTO) on bowel anastomosis after concomitant segmental left colonic resections achieved in rats. There were three separate groups of animals; each consisted of 20 Sprague-Dawley male rats weighing 250 +/- 20 g. In group I, left colonic segmental resection 1 cm in diameter and anastomosis were performed as controls. In group II, the same surgical procedure was done after 15 minutes of PTO followed by 30 minutes of reperfusion. In group III, PTO time was held at 30 minutes. The rats were killed at days 4 and 7 to evaluate anastomotic healing, histological changes, bursting pressures, and serum levels of malondialdehyde (MDA) and hydroxyproline. In group II, the bursting pressures of anastomosis on days 4 and 7 were similar to group I; these pressures were significantly lower in group III (P < 0.001), whereas the hydroxyproline levels in group II were lower than group I and group III levels (P < 0.002). There were histopathological changes that support the data found in groups II and III. Serum MDA levels in groups II and III were significantly higher than in group I (P < 0.001). We observed that serum MDA levels peaked at day 4 and gradually decreased with a statistically significant difference at day 7. In conclusion, there were no negative effects of PTO on colonic anastomosis in group II. But in group III, with longer occlusion times, anastomotic healing was impaired and the mortality rate was higher.

Effect of topically applied charged particles on healing of colonic anastomoses.

HYPOTHESIS: Various forms of electrical stimulation can improve wound healing in different tissues, but their application to gastrointestinal tract healing has not been investigated. We assumed that positively charged diethylaminoethyl cross-linked dextran bead (diethylaminoethyl Sephadex [DEAE-S]) particles would have a beneficial effect on the healing of colonic anastomoses. DESIGN: Experimental animal study. SETTING: Animal research laboratory of a university hospital. ANIMALS: Forty female Wistar albino rats. INTERVENTIONS: Right colonic transection and anastomosis was performed in 5 animal groups. The control group received no treatment; the placebo group, methylcellulose gel; and the DEAE-S group, DEAE-S in methyl cellulose gel applied topically around the anastomoses. The fecal peritonitis (FP) group underwent cecal ligation and perforation simultaneously with the anastomosis to cause FP; the FP + DEAE-S group also received DEAE-S applied around the anastomoses. MAIN OUTCOME MEASURES: After the completion of postoperative day 4, all rats were killed. Anastomotic bursting pressures and hydroxyproline concentrations in perianastomotic tissue were measured and compared. RESULTS: Mean bursting pressures were 115.1 mm Hg in the control group, 113.6 mm Hg in the placebo group, 159.4 mm Hg in the DEAE-S group, 62.8 mm Hg in the FP group, and 121.1 mm Hg in the FP + DEAE-S group (P =.001, 1-way analysis of variance [ANOVA]). The differences between the control vs DEAE-S groups, placebo vs DEAE-S groups, and FP vs FP + DEAE-S groups were significant (P<.05, t test). Mean hydroxyproline concentrations were 5.2 microg/mg in the control group, 4.9 microg/mg in the placebo group, 5.6 microg/mg in the DEAE-S group, 4.5 microg/mg in the FP group, and 5.4 microg/mg in the FP + DEAE-S group (P =.09, 1-way ANOVA). The difference between the FP and FP + DEAE-S groups was significant (P =.04, t test). CONCLUSIONS: A positively charged particle, DEAE-S, improves healing of colonic anastomoses in healthy rats and in rats with FP. This inexpensive, nontoxic material is easily applied and deserves further evaluation in gastrointestinal tract healing.

Pinealectomy does not affect the healing of experimental colonic anastomoses.

Gastrointestinal system anastomoses, especially colonic anastomoses, have significant morbidity and mortality despite recent technical improvements. Besides regulating the circadian rhythm, the pineal gland and its main neurohormone product melatonin have widespread actions in the organism. The purpose of this study was to investigate the effects of pinealectomy on the healing of colonic anastomoses. One hundred male albino Wistar rats were used in this study. The rats were separated into three groups: control, pinealectomy, and sham groups. In the control group, only colonic resection and anastomoses were performed. Following pinealectomy, colonic anastomosis was performed 2 weeks later on one half and 2 months later on the other half of the pinealectomy group. Only craniotomy was performed on the sham group, and the rats were separated and evaluated like the pinealectomy group. Colonic anastomoses were evaluated on postanastomotic day 3 and 7 by measuring the bursting pressure and the hydroxyproline levels in the anastomotic segments. There was no difference in the bursting pressure measurements between the groups on both postoperative day 3 and 7. Although hydroxyproline levels were different between groups on both postanastomotic days 3 and 7, it has been observed that neither normal nor anastomotic hydroxyproline levels influenced the anastomotic bursting pressure measurements. The percent deviation from the normal values was compared in the anastomotic segments, and no differences were found regarding the bursting pressure and hydroxyproline levels. It was concluded that pinealectomy has no effect on the healing of colonic anastomoses.

The effects of corticosteroids on the healing of tracheal anastomoses in a rat model.

The deleterious effects of corticosteroids on anastomotic healing have been widely demonstrated in various tissues. This study is designed to investigate the effects of corticosteroids on the healing of tracheal anastomoses. Forty-two adult female Wistar rats, randomly divided into five groups, underwent tracheal transection and primary anastomoses. The groups were assigned as follows: Group I, sham, ( N= 6); Group II, control, ( N= 6); Group III, dexamethasone, 0.1 mg kg (-1) per day, intramuscularly for a week ( N= 10); Group IV, dexamethasone, 1 mg kg (-1) per day, intramuscularly for a week (N= 10); Group V, dexamethasone, 6 mg kg (-1) intramuscularly as a single dose ( N= 10). After 7 days, anastomotic healing was assessed by measurement of bursting pressure and hydroxyproline content. Histological examination was performed according to the modified Ehrlich/Hunt scale. The bursting pressure was significantly decreased in Group III and Group IV when compared to the control group (P< 0.0001 for both groups). There was also significance between the bursting pressures of Group III and Group IV (P< 0.01). However, the difference failed to reach significance between Group V and the control group. The reduction of bursting pressure was not reflected in diminished hydroxyproline content. The hydroxyproline content of the study groups (GIII, GIV and GV) were not statistically different compared with the control group. Except for inflammatory cell infiltration, histological parameters including epithelial regeneration, fibroblast proliferation, collagen content, and angiogenesis also demonstrated significant differences among the groups (P< 0.05). The present study demonstrates that daily administration of dexamethasone for a week significantly impairs the healing of tracheal anastomoses in a dose-dependent manner while a single-dose postoperatively does not affect the healing process.