Adrenomedullin expression in aortic artery wall of diabetic rats given alpha lipoic acid.

BACKGROUND: Diabetes mellitus (DM) is a major health problem predisposing to cardiovascular diseases. The aim of this study was to investigate the effects of alpha lipoic acid (ALA) on both the arterial wall of diabetic rats and the adrenomedullin (ADM) gene expression. METHODS: Twenty-four Wistar Albino rats were divided into three groups as Control, DM + S, and DM + ALA. For DM model, a single dose of 40 mg/kg streptozotocin, for DM + ALA group, 100 mg/kg/day/4 weeks was administered. Hematoxylin & Eosin (H&E) staining was done and vascular endothelial growth factor (VEGF) was detected by immunohistochemical analysis in the artery wall. Total damage score of vessel wall (endothelial cell damage, media layer smooth muscle cell damage, and internal elastic lamina damage) and H score (immunoreactivity intensity) were calculated. Expression of ADM gene was measured by qRT-PCR. RESULTS: In DM + S group, Total damage score of vessel wall were detected by light microscopy. There were statistically significant differences between the groups Control/DM + S and DM + S/DM + ALA in terms of the vessel total damage score and H score (p < 0.005). ADM expression was increased threefold in both DM + S and DM + ALA groups compared to the control group (p < 0.05). CONCLUSIONS: ALA may have positive effect on the vessel damage in diabetic rats. However, no significant decrease in ADM expression levels was observed in diabetic rats after ALA administration and we considered that the protective effect of ALA is independent of adrenomedullin. Further studies with different doses and durations of ALA administrations are required to investigate the changes in ADM expression.

Is mycophenolate mofetil an alternative agent to corticosteroids in traumatic nerve paralysis?

OBJECTIVE: The effects of an immunosuppressive agent, mycophenolate mofetil (MM), were investigated and compared with those of methylprednisolone (MP) and dexamethasone (DXM) on the traumatic nerve function. STUDY DESIGN: This is a randomized controlled animal study. MATERIALS AND METHODS: This experimental study was performed on 84 male Wistar albino rats. The rats were assigned to 12 groups each consisting of 7 animals. The groups were formed according to application of normal-dose DXM (group 1A-B), high-dose MP (group 2A-B), normal-dose MP (group 3A-B), MM (group 4A-B), and MM with high-dose MP combination therapies (group VA-B). Right sciatic nerve dissection was performed, and compound muscle action potential thresholds were recorded. The nerve was traumatized with the compression of a Jeweller forceps for 20 seconds. Posttraumatic thresholds were also recorded. The compound muscle action potential thresholds were recorded in the first and fourth weeks for the assigned groups. Then, the nerve was transected and prepared for electron microscopic and histopathologic examinations. Nitric oxide and malondialdehyde assessments were performed on both tissue and blood samples. RESULTS: Only the MM and MP+MM groups had satisfactory electron microscopic findings and were about to reach the tissue characteristics of the control animals. Despite the electrophysiologic recovery, the DXM group was found to have poor electron microscopic scoring. CONCLUSIONS: Mycophenolate mofetil has been found to be beneficial in the treatment of traumatic nerve paralysis. Although a complementary investigation is needed, this immunosuppressive agent may be an alternative to corticosteroids for the selected cases where steroid therapy is contraindicated.

Effects of α-MSH on ischemia/reperfusion injury in the rat sciatic nerve.

BACKGROUND: Ischemia/reperfusion (I/R) causes the production of toxic free radicals and leads to pathological changes in nerve tissue. We investigated the effect of alpha-melanocyte stimulating hormone (α-MSH) in a rat model for sciatic nerve I/R and discuss the possible cytoprotective and antioxidant mechanism of α-MSH against ischemic fiber degeneration. METHODS: Experiments were performed using 42 adult male Wistar rats. Rats were divided into six experimental groups: control group, ischemia group, I/R groups, and α-MSH treated groups. Ischemia was produced by clamping of the femoral vessels. Immediately after ischemia that lasted 3 h, 75 µg/kg of α-MSH was administered subcutaneously before reperfusion and the tissue malondialdehyde (MDA) level was evaluated as an indicator of lipid peroxidation in groups with different reperfusion periods. RESULTS: The reperfusion injury did not begin in the first hour of reperfusion after 3 h of ischemia, and MDA levels increased on the first day of reperfusion. During the first day, blood MDA levels were decreased in the α-MSH group compared to the control group. The tissue from animals pre-treated with α-MSH showed fewer morphological alterations. Myelin breakdown was significantly diminished after treatment with α-MSH, and the ultrastructural features of axons showed remarkable improvement. Two-way analysis of variance was used for comparing three or more groups. When a significant difference existed, the post-hoc multiple-comparison test was applied to demonstrate the differences. CONCLUSIONS: The results confirm that pre-treatment with α-MSH after ischemia protected the peripheral nerves against I/R injury.

Comparison of the effects of different electrocautery applications to peripheral nerves: an experimental study.

BACKGROUND: This study was designed to investigate the effects of bipolar and mononopolar electrocauterization on peripheral nerve tissue. The comparison on the deleterious effects of the different cautery modalities and the importance of probe tip placement are evaluated using electrophysiological, electron microscopic and biochemical assessment parameters. METHODS: Ninety-eight male Wistar albino rats, each weighing 250-275 g, were randomly divided into 14 groups. Each group consisted of seven animals. Monopolar and bipolar electrocautery were performed at 15 watts. The application was performed either directly on the nerve or 1 mm lateral to the longitudinal axis of the nerve for 'near the nerve groups', respectively. RESULTS: The electrophysiological findings showed that the mean amplitudes were at the lowest value in the first day for all the groups. At the end of the 3rd week, we recognised that the electrophysiological recovery continued. Electron microscopic evaluation showed myelin disruption in all groups. Myelin disruption of healthy neurons was at the highest level in the 1st day of application in accordance with the electrophysiological findings. Biochemical evaluation revealed statistical significance between the control and the two of the 'near the nerve groups' (GIII and GV) for NO (nitrite and nitrate) serum level. CONCLUSION: The data of the present study might suggest that electrocautery, independent of the type and form of application, may result in significant damage in histological and electrophysological basis. Although the relative proportions cannot be ascertained, the time course of recovery suggests that both axon and myelin damage have occurred. The probable electrocautery damage may be of substantial importance for the situation that the nerves are displaced by tumor masses or atypical neural traces.

Effects of peripheral nerve ischemia-reperfusion model on serum cytokine levels.

AIM: Although the neuropathology of ischemic nerve fiber degeneration is relatively well known, its pathogenesis is poorly understood. Local cytokines, which have neuroprotective effects on inflammation and repair, participate in the process by undefined mechanisms. In this study, we evaluated the effects of ischemia and reperfusion on the sciatic nerve of the rat and investigated the probable effects of cytokines on this period. MATERIAL AND METHODS: In the current study, ischemia and reperfusion injury of sciatic nerve was rendered by clamping the femoral artery and vein of the rat for three hours and was followed by varying durations of reperfusion. Activin A, TGF Beta1 and TGF, Beta2 levels were measured in serum samples. RESULTS: TGF Beta1 and Activin A were found to be increased in the ischemic groups compared with the control group (p < 0.05). A significant difference was found between the experimental groups after reperfusion (p < 0.05). There was no statistical significance for TGF Beta2 levels between the study groups (p > 0.05). CONCLUSION: Ischemia causes some important changes in biochemical parameters, and nerve injury continues for a while according to the reperfusion time. Ischemia-reperfusion injury of peripheral nerves caused by various reasons therefore affects the levels of cytokines.

Genetic polymorphism of VEGF-1154 (A/G) in laryngeal squamous cell carcinoma.

BACKGROUND: Angiogenesis has been shown to be increased in various human tumors including head and neck squamous cell carcinoma (SCC). Vascular endothelial growth factor (VEGF) is thought to be one of the most important angiogenic factors in tumorigenesis. In this study, we aimed to investigate whether polymorphism of VEGF-1154 (A/G) genotypes are associated with the risk of laryngeal SCC. METHODS: A prospective, randomized, case-control study in a tertiary university hospital was done. The study group consisted of 57 Caucasian patients with laryngeal SCC and 89 control subjects. Blood samples were obtained before surgery or from the patients under follow-up to 5 years after surgery. VEGF-1154 (A/G) genotypes were detected by real-time polymerase chain reaction with thermal cycler system. RESULTS: According to the high-risk (GG) genotype, the difference between the patient and control groups was statistically significant (OR 0.43, 95% CI=0.19-0.95, p=0.037). CONCLUSIONS: GG genotype of the VEGF gene may increase the risk of laryngeal SCC in this population. VEGF gene polymorphism may be an important potential genetic and therapeutic marker of laryngeal SCC.

The effect of remote ischemic preconditioning on healing of colonic anastomoses.

BACKGROUND: We aimed to investigate the potential protective effect of remote ischemic preconditioning (IPC) on delayed colonic anastomotic healing induced by remote ischemia and reperfusion (I/R) injury. MATERIALS AND METHODS: Forty male Wistar rats were randomly assigned into four groups, each consisting of 10 rats: the control group (C), the remote I/R group [I/R, 40 min of superior mesenteric artery (SMA) occlusion], the preconditioned I/R group (IPC, two cycles of 5 min temporary occlusion of SMA before an ischemic insult of 40 min), and the preconditioned group (PC, two cycles of 5 min temporary occlusion of SMA). Colonic anastomosis was performed immediately after the ischemic insult. Anastomotic healing was assessed on postoperative day 7 by determining anastomotic bursting pressure (ABP), tissue hydroxyproline content, histopathological examination, malondialdehyde (MDA), and nitric oxide levels. RESULTS: Remote I/R injury resulted with significant impairment in anastomotic healing in terms of mean ABP (P = 0.004), hydroxyproline content (P = 0.002), histopathological healing score (P = 0.001), nitric oxide level (P = 0.010), and MDA levels (P = 0.0001) when compared with the control group, but remote IPC did not improve all above mentioned parameters (P = NS for all), except MDA level (P = 0.011) when compared with I/R group. PC alone impaired the ABP (P = 0.0001), but it did not significantly change the other parameters measured (P = NS). CONCLUSIONS: The results of this study showed that remote IPC did not prevent I/R-induced delaying in colonic anastomotic healing.

The role of apoptosis in traumatic versus nontraumatic nasal septal cartilage.

BACKGROUND: Nasal surgery is occasionally performed to correct traumatic nasal deformity. Septal cartilage is the main tissue to be corrected and is a graft source when needed. A risk in engrafting with cartilage is the possibility of resorption as a result of either necrosis or apoptosis. The authors evaluated the rate of apoptosis in deviated and straight cartilage to investigate the cause of resorption of cartilage tissue. METHODS: Twenty-five patients with traumatic nasal septum deviation (group I) and 13 patients with nontraumatic nasal septum deviation (group II) were prospectively enrolled. After correction of the deviation, two small samples of cartilage were harvested, one from the deviated site (group Ia or IIa) and the other from the straight site (group Ib or IIb), immediately frozen at -70 masculineC, and evaluated for apoptosis using DNA agarose gel electrophoresis. RESULTS: Apoptosis was detected in 14 (56 percent) of the deviated and two (8 percent) of the straight cartilage samples in traumatic patients, whereas it was detected in only one deviated sample (7.7 percent) and none of the straight samples in nontraumatic patients. The apoptosis rates in group Ia were statistically significant when compared with groups Ib (p = 0.0007) and IIa (p = 0.0007). CONCLUSIONS: The present study demonstrates that apoptosis occurs in traumatized nasal septal cartilage. Apoptosis might be the factor leading to cartilage resorption, weakness, and warping when used as a graft. Thus, cartilage grafting materials should be taken from the nontraumatized portion of the septum and should not be traumatized either during harvesting or before placement.

The effect of octreotide on healing of injured colonic anastomosis with immediate postoperative intraperitoneal administration of 5-Fluorouracil.

PURPOSE: This study was designed to investigate the effect of octreotide on side effects of immediate usage of 5-fluorouracil after colonic anastomosis. METHODS: Forty male Wistar rats were randomly assigned into four groups and underwent standardized left colonic anastomosis. The rats served as control or received intraperitoneal 5-fluorouracil (20 mg/kg daily), subcutaneous octreotide (20 mug/kg daily), or both. Diarrhea and wound complications were noted during the experiment. The colonic anastomoses were assessed for healing on postoperative Day 7 by determining the anastomotic bursting pressure, performing histologic examination, and measuring the tissue hydroxyproline content, serum malondialdehyde, and nitric oxide levels. Intraperitoneal adhesions and anastomotic leakage were also noted. RESULTS: No statistical significant difference was found between the control and octreotide groups for each of the parameters measured. Immediate 5-fluorouracil use resulted with higher adhesion score (P = 0.002), significant depression in anastomotic bursting pressure (P = 0.0001), histopathologic score (P = 0.0001), hydroxyproline content (P = 0.0001), and increasing nitric oxide (P = 0.0001) and malondialdehyde levels (P = 0.0001) compared with the control group. Diarrhea was seen in 80 percent of the 5-fluorouracil group but in neither the control nor octreotide groups (P = 0.0001 for each comparison). However, all these parameters were ameliorated by use of concomitant octreotide and 5-fluorouracil (P = 0.019, P = 0.023, P = 0.0001, P = 0.006, P = 0.0001, and P = 0.013, respectively). In addition, diarrhea was found to be prevented (P = 0.0001). CONCLUSIONS: The results of this study showed that concomitant octreotide use might prevent the side effects of 5-fluorouracil, such as diarrhea, postoperative adhesion, and delaying the anastomotic healing parameters. In addition, it might reduce tissue damage and inflammation.

Roles of nitric oxide, malondialdehyde, and fibronectin in an experimental peripheral nerve ischemia-reperfusion model.

Although there are many studies of the neuropathology of the ischemic degeneration of peripheral nerves, the pathogenesis is not well-understood. The roles of several biomolecules on this process were previously reported. An adhesion molecule, fibronectin, which is applied locally (as a conduit material), is very effective in nerve recovery. This study was carried out to evaluate the roles of fibronectin, lipid peroxidation, and nitric oxide (NO) in an experimental model of peripheral nerves. Ischemia and reperfusion injury of sciatic nerves was rendered by clamping the femoral artery and vein. Rats were divided into nine groups. Ischemia and reperfusion were not applied to group 1. In group 2, only ischemia was performed, but reperfusion was not accomplished. For groups 3-9, 1, 2, and 24 h and 1, 2, 3, and 4 weeks of reperfusion were applied following 3 h of ischemia. Then NO, malondialdehyde (MDA), and fibronectin levels were observed in serum samples of rats. Colorimetric and nephelometric assays were used for determination of the levels of these parameters. In this study, all biochemical parameters were found to be increased in the ischemia groups when compared with the control group 1 (P < 0.05). A significant difference was observed between study groups with respect to MDA, NO, and fibronectin levels (P < 0.05). Also, some correlations were established between biochemical parameters in the same group, depending on the varying reperfusion time (r > 0.50). Ischemia causes some important changes in biochemical parameters, and depending on the reperfusion time, nerve injury continues for a while. In our study, we observed that serum levels of MDA decreased in the periods when NO and fibronectin simultaneously increased. Such increases may contribute to neural recovery, and there may be interactions among them.

N-acetylcysteine protects the rats against phrenic nerve dysfunction in sepsis.

This study investigates the association of oxidative stress with the function of the phrenic nerve and inquires whether N-acetylcysteine (NAC) may counteract the possible detrimental effects. Thirty rats were divided into three groups: sham, cecal ligation and puncture (CLP), and CLP plus NAC treatment. Sepsis was produced by the CLP procedure. NAC was administered at 70 mg/day for 7 days. Electrophysiology was evaluated by the needle electromyography of the diaphragm and phrenic nerve conduction study. Oxidative stress was evaluated by malondialdehyde (MDA), nitrite/nitrate (NN), and reduced-glutathione (ReGSH) levels and myeloperoxidase (MPO) and catalase (CAT) activities in the phrenic nerve. In the CLP group, ReGSH and CAT were decreased (P = 0.0001, P = 0.07, respectively); and MDA, MPO, and NN were increased (P = 0.02, P = 0.0001, P = 0.043, respectively), compared with the sham group. NAC administration increased the ReGSH (P = 0.036) and decreased the MDA, MPO, and NN (P = 0.008, P = 0.01, P = 0.032, respectively), compared with the CLP group. In the CLP group, electrophysiology revealed reductions in the number of motor unit action potentials (P = 0.0001) and prolongations in the latency of the compound nerve action potential (P = 0.0001), indicating phrenic nerve neuropathy. NAC administration significantly ameliorated these electrophysiological alterations (P = 0.011, P = 0.0001, respectively), compared with the CLP group. The present results showed that intraabdominal sepsis is closely associated with phrenic nerve neuropathy. In addition, NAC administration protects the rats against the detrimental events of sepsis.

Effects of trapidil after crush injury in peripheral nerve.

In this study, we evaluated the effects of trapidil on crush injury by monitoring nitric oxide, malondialdehyde and transforming growth factor-Beta2 levels and by transmission electron microscopy in the rat sciatic nerve. The sciatic nerve was compressed for 20 sec by using a jewelers forceps. Trapidil treatment groups were administrated a single dose of trapidil (8 mg/kg) intraperitoneally just after the injury. The crush and crush + trapidil treatment groups were evaluated on the 2nd, 7th, 15th, 30th and 45th days of the post-crush period. On the 7th and 15th days, damage in thin and thick myelinated axons, endoneural edema and mitochondrial swelling were less severe in the trapidil group histopathologically. These findings supported the idea that trapidil prevented cell damage and edema at the injury site. Day/group interaction with regard to serum nitric oxide, malondialdehyde and transforming growth factor-Beta2 levels did not show significant changes.

The role of fibronectin and nitric oxide (NO) in gastrointestinal cancers.

BACKGROUND/AIMS: Gastrointestinal cancers are one of the most common malignancies in the world. Various etiologic factors have been proposed including viruses, chemical agents, and genetic factors. The aim of this study was to investigate the role of fibronectin (FN) and nitric oxide (NO) in gastric and colorectal cancers. METHODOLOGY: Thirty-nine patients (22 males, 17 females) with colorectal, 18 (10 males, 8 females) with gastric cancer, and 22 healthy control subjects were included in the study. The Griess reaction was used for the measurement of NO levels. An immunochemical reaction was used for measurement of FN levels. RESULTS: We found increased levels of NO in colon and gastric cancer, and decreased levels of FN in colon cancer when compared with healthy control subjects. Neither FN nor NO levels were associated with age, gender, stage of disease and survival status. No significant association was found between NO and FN levels. CONCLUSIONS: In conclusion, these two molecules might contribute to the pathogenesis of gastrointestinal cancers. The combination with standard chemotherapy and nitric oxide synthase inhibitors may be useful for the treatment of gastrointestinal cancer.

Protective effect of L-carnitine on renal ischaemia-reperfusion injury in the rat.

This study was designed to investigate the effect of L-carnitine in ischaemia and reperfusion of the rat kidney. Rats were randomly allocated into three groups. Group I (control group; n = 6) received no treatment. Group II (isotonic saline group; n = 6), received 2 ml of isotonic saline 15 min before the renal ischaemia, and group III (carnitine group; n = 6) received L-carnitine hydrochloride (100 mg kg(-1)) intraperitoneally. At the end of the reperfusion period, rats were sacrificed. Tissue malondialdehyde level (MDA), myeloperoxidase (MPO) activity, and nitrite/nitrate (NO) level of renal tissue were measured to evaluate the lipid peroxidation, neutrophil function, and nitric oxide metabolism, respectively. The tissue levels of MDA, MPO and NO were lower in group III (71.8 +/- 8.4, 172.1 +/- 27.4 U g(-1) tissue, 76.3 +/- 29.7 micromol l(-1) respectively) than levels in groups I (103.4 +/- 13.4 nmol g(-1), 325.9 +/- 20.2 U g(-1) tissue, 144.5 +/- 39.2 micromol l(-1), respectively) and II (103.5 +/- 11.4 nmol g(-1), 317.1 +/- 41.5 U g(-1) tissue, 148.9 +/- 23.9 micromol l(-1), respectively). It is shown that carnitine protects kidney tissue against ischaemia-reperfusion injury.

Effects of triazolopyrimidine on lipid peroxidation and nitric oxide levels in the corticosteroid-impaired healing of rat tracheal anastomoses.

Corticosteroids are used to reduce the oedema and prevent scar tissue formation of the upper airways by their ability to inhibit influx of inflammatory cells, limit capillary permeability and block collagen synthesis in the early stages of wound healing. Triazolopyrimidine (Trapidil) is an antiplatelet agent that acts in part as a phosphodiesterase inhibitor and as a competitive inhibitor of the platelet-derived growth factor (PDGF) receptor. Trapidil, with its vasodilator and NO releasing effect may have some potential to diminish the tissue injury. This study was carried out to evaluate the effects of trapidil (triazolopyrimidine) on lipid peroxidation and nitric oxide in the corticosteroid-impaired healing of tracheal anastomoses. Thirty-four adult Wistar rats were divided into five groups. The animals underwent tracheal transection and primary anastomoses. The groups were assigned as follows: group I, control, (GI, n = 6); group II, sham, (GII, n = 6); group III, dexamethasone, 0.1 mg kg(-1) twice daily intramuscularly, (GIII, n = 8); group IV, trapidil, 6 mg kg(-1) twice daily intraperitoneally (GIV, n = 7); group V, dexamethasone, 0.1 mg kg(-1) plus trapidil, 6 mg kg(-1) twice daily (GV, n = 7), for 1 week. After 1 week, anastomotic healing was assessed by measurement of bursting pressure, evaluation of histopathology, measurement of MDA and nitrite/nitrate levels. In GIII, GIV and GV bursting pressures resulted in significantly reduced anastomotic strength compared to the controls (p < 0.001 for all groups). The difference between bursting pressures of GIII and GIV was not found to be statistically significant (p = 0.966). In regard to fibroblast proliferation and collagen content, a significant difference was found between GIII and GI (p < 0.01), A significant difference was also found when GIV and GV were compared to GIII (p < 0.01). MDA and nitrite/nitrate levels were found to be higher in GIII when compared to all other groups. MDA levels of GIV and GV rats were found to be lower than GIII (p < 0.001, for both groups). The nitrite/nitrate levels of GIV and GV rats were found to be lower than GIII (p < 0.05), and higher than GI (p < 0.001). Trapidil may be useful for its preventive effects on lipid peroxidation and possible increases in NO in cases with corticosteroid-impaired healing of trachea anastomoses.

The effect of alprostadil on ischemia-reperfusion injury of peripheral nerve in rats.

OBJECTIVE: To determine the effect of alprostadil on the ischemia-reperfusion (I/R) injury of the sciatic nerve in rats. MATERIALS AND METHODS: Pre-reperfusion administration of alprostadil (0.05 microg kg(-1)) was assessed in the I/R injury model of the rat sciatic nerve. In this model, blood samples were investigated for the I/R injury markers namely malondialdehyde (MDA), an indicator of lipid peroxidation, and nitrite/nitrate levels, products of nitric oxide (NO) metabolism. RESULTS: A significant decrease in MDA, and increase in NO levels were observed in the groups which received alprostadil before reperfusion, when compared to their corresponding untreated controls (I/R only) at all time intervals (P=0.0001). There was a statistically significant difference in both MDA, and NO levels between certain time intervals. There was no statistical linear correlation between MDA and NO levels. CONCLUSION: Alprostadil may be suggested as a protective anti-inflammatory and a vasodilator pharmacological agent for I/R injury in peripheral nerves. Also, measurements of NO and MDA may be complementary to the generally accepted evaluation parameters of I/R injury including electromyography and nerve histopathology.

Bronchoscopy induces intestinal mucosal barrier dysfunction: a possible role for nitric oxide.

OBJECTIVE: This study investigates the effect of bronchoscopy on intestinal mucosal barrier function and its association with intestinal nitric oxide production. METHODS: 30 rats were used. The study group (n=15) underwent rigid bronchoscopy. At 24 h following bronchoscopy, ileal nitrite/nitrate levels were evaluated. The ileum was also examined for mucosal damage, and graded according Chiu's histologic injury scale. RESULTS: In the bronchoscopy group, the ileal nitrite/nitrate levels were significantly higher than those of controls (398.5 +/- 85.1 and 44.5 +/- 6.6 nmol/g tissue, respectively, P=0.001). In the bronchoscopy group, the mucosal damage was significant, compared with those of controls (mean ranks, 22.8 and 8.2, P<0.0001). The changes varied from denuded villi and dilated capillaries to significant architectural distortion, lamina propria disintegration, ulceration and hemorrhage. Significant correlation was found between ileal nitrite/nitrate levels and mucosal damage in the bronchoscopy group (rs=0.56, P=0.03). CONCLUSION: This study suggests that bronchoscopy induces intestinal mucosal barrier dysfunction in association with excess intestinal nitric oxide production. These events may be involved in mechanisms responsible for bacterial translocation after bronchoscopy.

Effect of trapidil in ischemia/reperfusion injury on rat small intestine.

To investigate the effect of trapidil on the intestinal ischemia-reperfusion injury, we determined malondialdehyde levels as a indicator of lipid peroxidation, nitrite and nitrate levels as reflections of nitric oxide metabolism, and histopathological findings in rats subjected to 40 min of ischemia and 2 h of reperfusion. Histopathological evaluation demonstrated that trapidil treatment has a protective effect on intestinal mucosa and reduces inflammatory cell infiltration in lamina propria, which is consistently noted in the untreated ischemic and reperfused intestines. Possible mechanism of this effect may be explained by the reduced lipid peroxidation (mean malondialdehyde level 3.72 +/- 0.27 vs. 6.13 +/- 0.44, p <.0001) and improved nitric oxide metabolism (mean nitrite plus nitrate 38.21 +/- 2.33 vs. 30.14 +/- 1.47, p =.022).

The effects of carnitine on distally-burned dorsal skin flap: an experimental study in rats.

OBJECTIVE: In ischemia and burn injuries, there are major alterations threatening tissue survival. Increased energy flow requirements are among the major problems in these disorders. Carnitine is an endogenous cofactor, which has a regulatory action on the energy flow from different oxidative sources. The purpose of this study was to determine the effects of carnitine in an experimental flap model. Biochemically, nitric oxide (NO), malondialdehyde (MDA), and acetylcholinesterase levels, and histopathologically tissue examination under light microscope were studied. METHODS: In the rat dorsal skin, a 10 cm x 3 cm flap was marked. The most distal 3 cm x 3 cm of the flap was burned to full-thickness. The dorsal flap was elevated, and sutured back to its original site. Sixteen rats were divided into two groups (a control (1) and a study group (2)), consisting of eight rats in each. While the animals in the control group were just followed, the animals in the study group were administrated carnitine with a dose of 100 mg/kg per day for 7 days. RESULTS: At the end of the experiment: the mean surviving areas of the flaps were 15.22 cm(2) (50.73%) in group 1, 20.53 cm(2) (68.43%) in group 2, and the difference was statistically significant (P=0.008). In the analysis of blood samples; the mean levels of NO were 22.63 and 40.78 micromol/l; of MDA were 6.74 and 3.79 ng/ml; and of acetylcholinesterase were 136.14 and 222.85 U/l in groups 1 and 2, respectively. The differences in the levels of NO (P=0.001), MDA (0.027) and acetylcholinesterase (P=0.006) were statistically significant. Histopathological examination revealed a full-thickness muscle necrosis in addition to skin tissue in the control group, while healing tissue was present with marked cellularity including mixed inflammatory cells and fibroblast proliferation with an increased vascularity in the form of capillary budding in the study group. CONCLUSION: Carnitine has a positive effect in such a model, particularly in preventing the progressive effect of burn, and limiting the necrosis in the full-thickness burned part.

Effects of trapidil on intestinal mucosal barrier function and bacterial translocation after intestinal ischemia and reperfusion in an experimental rat model.

BACKGROUND: Intestinal ischemia and reperfusion may be the primary triggers of mucosal barrier impairment, cytokine expression, and bacterial translocation (BT). Trapidil is a phosphodiesterase and platelet-derived growth factor inhibitor that reduces lipid peroxidation and inhibits the production of cytokines. OBJECTIVE: The goal of this study was to assess whether trapidil might protect the intestinal epithelial barrier by inhibiting lipid peroxidation and proinflammatory cytokines by testing the effect of trapidil on intestinal barrier function in an experimental ischemia/reperfusion (I/R) rat model. METHODS: Trapidil was used in a rat model of intestinal barrier dysfunction caused by intestinal ischemia for 40 minutes followed by reperfusion for 12 hours. To do this, the rats were randomized to 1 of 4 treatment groups, as follows: (1) sham surgery and saline administration (1 mL IV) (Sham group); (2) sham surgery and trapidil administration (8 mg/kg IV) (Sham+T group); (3) I/R and saline administration (1 mL IV) (I/R group); and (4) I/R and trapidil administration (8 mg/kg IV) (I/R+T group). Intestinal barrier function was assessed by histopathologic examination, blood malondialdehyde (MDA) level, and BT. RESULTS: The I/R+T group showed significantly less incidence of BT compared with the I/R group in the liver and reduced median colony count of translocated bacteria in mesenteric lymph nodes, liver, spleen, and peritoneum compared with the I/R group. Furthermore, the mean blood MDA level demonstrated that lipid peroxidation was significantly decreased in the I/R+T group compared with the I/R group. Histopathologic findings revealed that trapidil administration before reperfusion preserved intestinal mucosal integrity and inhibited the infiltration of inflammatory cells into the intestines. CONCLUSIONS: In this experimental study, a correlation seemed to exist between intestinal barrier dysfunction and BT. Intestinal barrier dysfunction may allow a large amount of bacteria to pass from the gut to distant organs. Trapidil treatment may inhibit BT by preserving intestinal barrier by inhibiting thromboxane A2, lipid peroxidation, proinflammatory cytokines, and stimulated prostacyclin. Future dose- and time-dependent studies will be helpful in revealing the effects of trapidil on BT.