Effects of trapidil on renal ischemia-reperfusion injury.

There is increasing evidence to suggest that reactive oxygen and nitrogen species play a role in the pathogenesis of renal ischemia-reperfusion (I/R) injury. This study was designed to determine the possible protective effects of trapidil treatment against oxidative and nitrosative tissue injury of kidney induced by I/R. A renal I/R injury was induced by a left renal pedicle occlusion by ischemia for 45 minutes, followed by 1 hour of reperfusion with contralateral nephrectomy in I/R and I/R + trapidil groups. Trapidil (8 mg/kg intravenously) was administrated immediately before reperfusion phase. At the end of the reperfusion period, rats were killed. Then, renal tissue samples were taken for biochemical analysis and histopathological evaluation, and blood samples were obtained to determinate serum urea, aspartate aminotransferase (AST), and tumor necrosis factor-alpha (TNF-alpha) levels. Ischemia-reperfusion injury caused significant increases in myeloperoxidase activity and malondialdehyde and 3-nitrotyrosine levels in renal tissue and elevated serum urea, AST, and TNF-alpha levels. In addition, severe deterioration of renal morphology was seen in the I/R group. Trapidil treatment significantly reduced in biochemical parameters, as well as serum urea, AST, and TNF-alpha levels. Furthermore, renal tissue injury was markedly attenuated with trapidil treatment. These data suggest that reactive oxygen species and reactive nitrogen species play a causal role in I/R-induced renal tissue, and trapidil has a renoprotective effect against oxidative and nitrosative kidney damage.

[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.

Protective effect of trapidil against oxidative organ damage in burn injury.

Animal models of thermal injury indicate reactive oxygen species and inflammatory cytokines as causative agents in tissue injury on various organs distant from the original wound. Trapidil has various properties, such as inhibition of platelet aggregation and lipid peroxidation as well as reduction of the inflammatory response to injury. This study was designed to determine the possible protective effect of trapidil treatment against oxidative organ damage in lung, intestine and kidney induced by cutaneous thermal injury. Thirty Wistar rats were randomly divided into five groups. Sham group (n=6) was exposed to 21 degrees C water while burn-3 h group (n=6) and burn+trap-3h group (n=6), burn-24 h (n=6) and burn+trap-24 h groups were exposed to boiling water for 12s to produce a full thickness burn in 35-40% of total body surface area. In both burn+trap-3 h and burn-trap-24 h group, 8 mg/kg trapidil was given intravenously immediately after thermal injury. Three and 24 h later, tissue samples were taken for biochemical analysis from lung, intestine and kidney and blood samples were obtained to determinate serum TNF-alpha levels. Cutaneous thermal injury caused a significant increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) and 3-nitrotyrozine (3-NT) levels in all tissues and elevated serum TNF-alpha levels at post-burn 3 and 24 h. Trapidil treatment significantly reduced in biochemical parameters, as well as serum TNF-alpha levels. These data suggest that trapidil has a protective effect against oxidative organ damage in burn injury.

Poly (adp-ribose) synthetase inhibition reduces oxidative and nitrosative organ damage after thermal injury.

Poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme activated by DNA single-strand breakage, which can be triggered by reactive oxygen and nitrogen species. Activation of this enzyme depletes the intracellular concentration of energetic substrates such as nicotinamide adenine dinucleotide (NAD). Eventually, this process results in cell dysfunction and cell death. PARS inhibitors have successfully shown benefits in several experimental models of ischemia-reperfusion injury, inflammation, and sepsis. In our experimental study, we investigated the role of 3-aminobenzamide (3-AB), a nonspecific PARS inhibitor, in systemic organ damage after burn. Twenty-four Wistar rats were randomly divided into three groups. The sham group (n=8) was exposed to 21 degrees C water, and the burn group (n=8) and the burn-plus-3-AB group (n=8) were exposed to boiling water for 12 s to produce a full-thickness burn of 35-40% of total body surface area. In the burn-plus-3-AB group, 3-AB 10 mg/kg was given intraperitoneally 10 min before thermal injury. Twenty-four hours later, tissue samples were obtained for biochemical analysis from lung, intestine, and kidney. In the burn group, tissue malondialdehyde, myeloperoxidase, and 3-nitrotyrosine levels in all organs were significantly increased compared with the sham group (p<0.05). Pretreatment with 3-AB significantly reduced burn-induced organ damage (p<0.05). These data provide evidence of the relationship between the PARS pathway and lipid peroxidation in systemic organ damage after thermal injury.

An unusual cause for massive upper gastrointestinal bleeding in children: Dieulafoy's lesion.

Dieulafoy's lesion is a rare cause of severe upper gastrointestinal hemorrhage in children and predominantly occurs in the proximal stomach. We report a case of massive upper gastrointestinal bleeding in a 3-year-old boy that originated from a Dieulafoy's lesion and was treated by epinephrine injection.

The protective effect of selenium on ipsilateral and contralateral testes in testicular reperfusion injury.

This study was designed to investigate the effect of selenium on ipsilateral and contralateral testicular damage after unilateral testicular torsion/detorsion (T/D). Thirty-two male rats were divided into four groups, each containing eight rats. Torsion was created by rotating the right testis 720 degrees in a clockwise direction. Group 1 underwent sham operation to determine basal values for biochemical and histopathological evaluation. Sham operation was performed in group 2, and sodium selenate (0.2 mg/kg) was given intraperitoneally. Group 3 served as a T/D group, receiving 4-h torsion and 4-h detorsion. Similarly, in group 4 sodium selenate (0.2 mg/kg) was injected intraperitoneally 20 min before detorsion. Bilateral orchiectomies were performed for measurement of tissue malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities and histopathologic examination. The results were compared statistically. The highest MDA and the lowest SOD values were determined in both testes in group 3. There were statistically significant differences in MDA levels and SOD activities in group 3 compared with group 4. Specimens from group 3 had a significantly greater histologic injury than other groups. These results suggest that ischemia-reperfusion injury occurred in both testes after unilateral testicular T/D and that selenium administration before detorsion prevents reperfusion injury in testicular torsion.

The role of poly(ADP-ribose) synthetase inhibition on the intestinal mucosal barrier after thermal injury.

Oxidative and nitrosative stressor agents can trigger DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) synthetase (PARS). Activation of the enzyme depletes the intracellular concentration of energetic substrates such as nicotinamide adenine dinucleotide (NAD). This process can result in cell dysfunction and cell death. PARS inhibitors have been successfully used in ischemia-reperfusion injury, inflammation and sepsis in several experimental models. In our experimental study, we investigated the role of 3-aminobeanzamide (3-AB), a non-specific PARS inhibitor, on the intestinal mucosal barrier after burn injury. Twenty-four Wistar rats were randomly divided into three groups. The sham group (n = 8) was exposed to 21 degrees C water while the burn group (n = 8) and the burn + 3-AB group (n = 9) were exposed to boiling water for 12s to produce a full thickness burn in 35-40% of total body surface area. In the burn + 3-AB group, 10mg/kg of 3-AB was given intraperitoneally 10min before thermal injury. Twenty-four hours later, tissue samples from mesenteric lymph nodes (MLN), spleen and liver were obtained under sterile conditions for microbiological analysis and ileum samples were obtained for biochemical and histopathological analysis. In burn group, the incidence of bacteria isolated from MLN and spleen was significantly higher than other groups (P < 0.05). 3-AB pre-treatment prevented burn induced bacterial translocation and it significantly reduced burn induced intestinal injury. Tissue malondialdehyde and 3-nitrotyrozine levels were found significantly lower than that of the burn group. These data suggest that the relationship between PARS pathway and lipid peroxidation in intestinal tissue and PARS has a role in intestinal injury caused by thermal injury.

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.

Ischemic preconditioning reduces intestinal epithelial apoptosis in rats.

Recent experimental studies have described protective effect of ischemic preconditioning (IPC) on ischemia-reperfusion (I/R) injury of the intestine. We hypothesize that to reach a new point of view on the effect of IPC in intestinal barrier function, the relationship between I/R-induced mucosal injury and apoptosis must first be clarified. The present study was undertaken to investigate the role of IPC on intestinal apoptosis and probable contributions of bcl-2 expression to this process. We also investigated the effect of intestinal IPC on ileal malondyaldihyde levels. Forty-four male Wistar rats were randomized into four groups each consisting of 11 rats: sham-operated control, I/R group (30 min of superior mesenteric artery occlusion), IPC-I/R group (10 min of temporary artery occlusion prior before an ischemic insult of 30 min), and IPC alone group (10 min of preconditioning). Twenty-four hours later, ileum samples were obtained. Ileal malondyaldihyde levels were increased in the I/R group (31.9 +/- 18.8 vs. 106.8 +/- 39.8) but not in the IPC alone and IPC-I/R groups (38.1 +/- 13.6 and 44.7 +/- 12.7; P < 0.01). The number of apoptotic cells was significantly lower in IPC-I/R group than that of I/R group, and these findings were further supported by DNA laddering and M30 findings. Diminished bcl-2 expression observed in the ileal specimens of I/R group was prevented by IPC. Our results indicate that IPC may provide a protective effect on ileal epithelium and that this effect is probably the result of a significant increase in the expression of bcl-2 after the insult. The reversal of apoptosis by IPC might help preserving the vitality of intestinal structures that have a critical function, cessation of which often leads to multiorgan dysfunction syndrome.

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.

Ileal atresia associated with a congenital vascular band anomaly: observations on pathogenesis.

We report the case of a newborn, who developed intestinal obstruction soon after birth. Exploratory laparotomy revealed a congenital vascular band anomaly extending from the antimesenteric border of the terminal ileum to the gallbladder in association with ileal atresia. Surgical intervention was performed for correction of the disorder. A review of the embryology and congenital vascular bands is presented together with discussion as to possible etiopathogenesis leading to small bowel atresia.

Intestinal ischemic preconditioning protects the intestine and reduces bacterial translocation.

Ischemic preconditioning (IPC) was first demonstrated in the heart, but this protective effect has been also recently described in the intestine. The aim of this study was to determine the effects of intestinal ischemic preconditioning on the morphology of intestine and bacterial translocation. Twenty-four male Wistar rats weighting 250 to 300 g were randomized into three groups. A control group of rats (n = 8) were subjected laparotomy. In an ischemic group (n = 8), laparotomy was performed and the superior mesenteric artery was occluded by an atraumatic clamp for 30 min. In the preconditioned group (n = 8), before the ischemia-reperfusion (I/R) period (as in ischemic group), rats were subjected to an initial 10 min of intestinal ischemia and 10 min of reperfusion. Twenty-four hours later, to evaluate whether the I/R induced intestinal injury and bacterial translocation (BT), tissue and blood samples were collected, and liver, spleen, and mesenteric lymph node specimens were obtained under sterile conditions for microbiological analysis. Samples of ileum were removed for both biochemical and histopathological evaluation. In the I/R group, the incidence of bacteria-isolated mesenteric lymph nodes, spleen, liver, and blood was significantly higher than other groups (P < 0.05). IPC prevented I/R-induced BT and it significantly reduced the I/R-induced intestinal injury (P < 0.05). Increased inducible nitric oxide (NO) synthase (iNOS) expression observed on the ileal specimens of the I/R group was found to be prevented by IPC. Our data suggest IPC as a key factor that reduces BT and iNOS activation in intestinal I/R. This is the first study showing that intestinal IPC blocks the cascade of events that causes BT and intestinal injury that may lead to sepsis.

Does menstrual flow exclude hematometra? A rare case of uterine anomaly presenting with anorectal malformation.

Hematometra, which is defined as accumulation of menstrual secretions in the uterine cavity, may not be diagnosed until the maturating adolescent fails to menstruate. Clinically, a lower abdominal mass and periodic abdominal pain may develop in these children after puberty. Here, a 13-year-old girl with menstrual flow who presented with symptoms of genital outflow tract obstruction is described.

Dexamethasone down-regulates endothelial expression of intercellular adhesion molecule and impairs the healing of bowel anastomoses.

OBJECTIVE: To find out the role of endothelial expression of intercellular adhesion molecule-1 (ICAM-1) in the healing of intestinal anastomoses in rats, and to establish the effects of peroperative treatment with corticosteroids. DESIGN: Experimental animal study. SETTING: University hospital, Turkey. MATERIAL: 78 Male Wistar rats. INTERVENTIONS: Rats were divided into four groups: Group I, colonic anastomosis only (=18); Group II, colonic anastomosis plus caecal ligation and puncture (=18); Group III, colonic anastomosis plus dexamethasone (=18); and Group IV, colonic anastomosis, plus caecal ligation and puncture, plus dexamethasone (=18). Six animals served as the sham group. The animals underwent bowel transsection and primary anastomosis Infection was produced by caecal ligation and puncture Preoperatively, dexamethasone was given intramuscularly in a dose of 2 mg/kg/day. MAIN OUTCOME MEASURES: After 1, 3 and 5 days, anastomotic healing and endothelial expression of ICAM-1 were measured microscopically. RESULTS: Anastomotic healing was significantly impaired in dexamethasone-treated animals, and endothelial expression of ICAM-1 was reduced. Endothelial expression of ICAM-1 was no higher in the infected group than in controls. Maximum expression of ICAM-1 on endothelial cells was seen on the first day in each group, and declined on the following days, although the sebsequent reduction in expression was not significant. CONCLUSION: Dexamethasone down-regulated expression of ICAM-1, which is important in migration of leucocytes from the circulation to the wound site, and significantly impaired the healing of intestinal anastomoses in rats.