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 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.

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.

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.

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.

The effects of dexamethasone on lipid peroxidation and nitric oxide levels on the healing of tracheal anastomoses: an experimental study in rats.

Corticosteroids are shown to have deleterious effects on wound healing for various tissues. Arginine metabolism and nitric oxide (NO) synthesis play an important role in many aspects of inflammation and wound healing. The study was designed to evaluate the relationship of dexamethasone impaired healing of tracheal anastomoses to NO metabolism and lipid peroxidation. Forty-two adult Wistar rats were randomly divided into five groups. The animals underwent tracheal transection and primary anastomoses. The groups were assigned as follows: Group I (GI) (sham, N = 6); Group II (GII) (control, N = 6); Group III (GIII), dexamethasone, 0.1 mg kg(-1) per day, intramuscularly for a week (N = 10); Group IV (GIV), dexamethasone, 1 mg kg(-1) per day, intramuscularly for a week (N = 10); Group V (GV), dexamethasone, 6 mg kg(-1) intramuscularly as a single dose (N = 10). After 7 days, bursting pressure was used to evaluate anastomotic healing. Serum nitrite/nitrate and malondialdehyde (MDA) levels were measured as an index of NO synthesis and lipid peroxidation, respectively. The bursting pressure significantly decreased in GIII and GIV when compared to the control group. The difference between GIII and GIV was also statistically significant. Nitrite/nitrate and MDA levels of GIII were found to be significantly higher than the control group. Also, the difference was found to be statistically significant between GIII and GIV in regard to nitrite/nitrate levels. The present study demonstrates that daily administration of dexamethasone for a week inhibits NO synthesis in a dose-dependent manner on tracheal anastomotic healing. Besides the generally accepted evaluation parameters including bursting pressure and hydoxyproline content; NO and MDA levels may be helpful in the assessment of wound healing especially for the investigation of impairment mechanism.