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Background: During preoperative radiotherapy, effective doses of ionizing radiation occasionally cause wound complications after subsequent surgery. This study was designed to determine the effects of intraperitoneally or orally administered N-acetylcysteine (NAC) on anastomotic healing of irradiated rats. Material & Methods: Forty Wistar albino rats were randomized into four groups containing 10 rats each. A 3 cm long surgical full-thickness midline laparotomy was performed to all groups (Groups 1-4). Group 1 was designed as a control group without radiation therapy and NAC treatment. Groups 2, 3 and 4 received a single abdominal dose of 10 Gy irradiation before laparotomy and groups 3 and 4 received oral and intraperitoneal NAC, respectively. Results: Group comparisons demonstrated that breaking strength was significantly higher in NAC treated rats. A statistically significant difference was determined in terms of superoxide dismutase (SOD), malondealdehyde (MDA) and glutation (GSH) values between groups (p<0.001). Nevertheless, advanced oxidation protein products (AOPP) levels were found to be similar between groups (p=0.163). Serum GSH and SOD levels were significantly higher in groups 3 and 4 when compared to group 2 (p < 0.05). Similarly, there was a significant increase in serum MDA concentration, predicting lipid peroxidation, in group 2 when compared to groups 1, 3 and 4 (p < 0.05). There was not a significant difference between Groups 3 and 4 regarding GSH, MDA, SOD, and AOPP levels. Histopathological analysis revealed that NAC administration, either orally or intraperitoneally, leads to a better incisional healing in terms of inflammation, granulation, collagen deposition, reepithelization and neovascularization. Conclusion: The present study supports the hypothesis that NAC administration alleviates the negative effects of radiotherapy on incisional wound healing by means of reducing oxidative stress markers and improving histologic parameters independent of the route of administration. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate matrix metalloprotease-1 (MMP-1), matrix metalloprotease-3 (MMP-3), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) levels in the eyelid skin and fibroadipose tissue in patients with inactive moderate-to-severe Graves' orbitopathy (GO)., Methods: This prospective study included 23 patients with inactive moderate-to-severe GO who underwent upper blepharoplasty and medial fat excision, and 22 age- and sex-matched healthy subjects. MMP-1, MMP-3, TNF-α, and IL-6 levels in the skin and fibroadipose tissue obtained during surgery were measured using the ELISA method., Results: The mean MMP-1 level in the eyelid skin ( p  = .003) and the mean MMP-3 level in the fibroadipose tissue ( p  = .04) were significantly lower in the GO group compared to the healthy control group. There were no differences in other mediators in both tissues between the two groups ( p  > .05)., Conclusions: The lower levels of proteolytic enzymes such as MMP-1 and MMP-3 in the eyelid skin and orbital fibroadipose tissue of patients with chronic inactive GO may play a role in the increase of collagen and glycosaminoglycans in orbital soft tissues.

Purpose: To evaluate serum and aqueous humor levels of fetuin-A in patients with pseudoexfoliation syndrome (PEXS) in comparison with those of age- and sex-matched healthy subjects., Materials and Methods: This prospective study included 25 patients with PEXS and 25 control subjects who were undergoing cataract surgery without any systemic or ocular disease. Aqueous humor and serum fetuin-A levels were measured with enzyme-linked immunosorbent assay method., Results: The mean age of the PEXS group (14 males, 11 females, n = 25) was 57.7 ± 6.9 years, and the control group (13 males, 12 females, n = 25) was 58.1 ± 5.7 years. There was no difference between the groups in terms of age (p = 0.77) and sex (p = 0.83). The mean serum fetuin-A level of the PEXS group did not differ from that of the control group (p = 0.53). The mean aqueous humor level of the PEXS group was significantly higher than that of the control group (p = 0.032). There were no significant correlations between aqueous humor and serum fetuin-A levels among patients with PEXS and control group (p > 0.05)., Conclusions: Increased levels of fetuin-A in aqueous humor of patients with PEXS may show the local effect of fetuin-A on the anterior segment. With considering the wide range of possible biological functions of fetuin-A in the pathogenesis of PEXS, further studies are needed to clarify the clinical relevance of these findings.

Purpose: Nitric oxide production can cause either apoptotic or necrotic cell death through oxidative stress. We aimed to investigate the nitrite oxide metabolites (NO x ) and nitrite levels in the aqueous humor of rabbit eyes after different methods of corneal collagen cross-linking (CXL)., Materials and Methods: Twenty-four eyes of 12 adult New Zealand rabbits were used. They were assigned into four groups, each including six eyes. Group 1 (control) consisted of eyes with no treatment. Group 2 received UV-A power setting at 3 mW/cm 2 for 30 minutes of continuous exposure and named as standard CXL group. Group 3 received UV-A power setting at 30 mW/cm 2 for 3 minutes of continuous exposure and named as accelerated CXL (A-CXL) group. Group 4 received UV-A power setting at 30 mW/cm 2 for 6 minutes of pulsed exposure (1 sec on, 1 sec off) and named as pulse-light accelerated CXL (PLA-CXL). Aqueous humors were aspirated from anterior chamber with a 27G needle after 1 hour UV-A exposure. NO x and nitrite levels were measured Results: The nitrite levels in aqueous humor were significantly increased in Group 2 and Group 3 when compared with Group 1 (p = 0.000, p = 0.036, respectively). When treatment modalities were compared with each other, high nitrite level in Group 2 was statistically significant when compared with Group 4 (p = 0.019). NO x levels were higher in Group 2 when compared with Group 1 (p = 0.006)., Conclusions: Numerous studies investigated the physiological and pathophysiological roles of NO. NO is considered one of the most important molecule for ocular health. According to NO x level in aqueous humor, it seems that PLA-CXL is the safest method due to the similar results with control group.

Vitiligo is an acquired epidermal pigment loss of the skin. Oxidative stress is one of the major theories in the pathophysiology of vitiligo. FOXO3A is the forkhead members of the class O (FOXO) transcription factors, and plays an important role in cell cycle regulation, apoptosis, oxidative stress, and DNA repair. The aim of our study was to investigate FOXO3A gene polymorphisms and FOXO3A protein levels, activities of superoxide dismutase (SOD) and catalase antioxidant enzymes in vitiligo patients and healthy controls. Moreover, the level of plasma advanced oxidation protein products (AOPP) in subjects was evaluated to understand the possible role of protein oxidation in disease etiology. Study groups included 82 vitiligo patients and 81 unrelated healthy controls. FOXO3A polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism method. FOXO3A levels and catalase activity were measured by ELISA whereas AOPP levels and SOD activity was measured by spectrophotometric analysis. We found a significant relationship between rs4946936 polymorphism of FOXO3A gene and vitiligo/active vitiligo patients (p=0.017; p=0.019 respectively), but not for rs2253310 (p>0.05). SOD activity and AOPP levels of vitiligo patient were increased compared with control group, whereas FOXO3A levels and catalase enzyme activity of vitiligo patient were decreased compared with control group (p<0.05). Our study indicates that rs4946936 of FOXO3A gene may associate susceptibility of vitiligo, especially active vitiligo. Moreover, our results confirm that oxidative stress may play a role in the pathophysiology of vitiligo. Further studies with larger samples are required to elucidate the role of FOXO3A in vitiligo., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: During preoperative radiotherapy, effective doses of ionizing radiation occasionally cause wound complications after subsequent surgery. This study was designed to determine the effects of intraperitoneally or orally administered N-acetylcysteine (NAC) on anastomotic healing of irradiated rats., Material & Methods: Forty Wistar albino rats were randomized into four groups containing 10 rats each. A 3 cm long surgical full-thickness midline laparotomy was performed to all groups (Groups 1-4). Group 1 was designed as a control group without radiation therapy and NAC treatment. Groups 2, 3 and 4 received a single abdominal dose of 10 Gy irradiation before laparotomy and groups 3 and 4 received oral and intraperitoneal NAC, respectively., Results: Group comparisons demonstrated that breaking strength was significantly higher in NAC treated rats. A statistically significant difference was determined in terms of superoxide dismutase (SOD), malondealdehyde (MDA) and glutation (GSH) values between groups (p<0.001). Nevertheless, advanced oxidation protein products (AOPP) levels were found to be similar between groups (p=0.163). Serum GSH and SOD levels were significantly higher in groups 3 and 4 when compared to group 2 (p < 0.05). Similarly, there was a significant increase in serum MDA concentration, predicting lipid peroxidation, in group 2 when compared to groups 1, 3 and 4 (p < 0.05). There was not a significant difference between Groups 3 and 4 regarding GSH, MDA, SOD, and AOPP levels. Histopathological analysis revealed that NAC administration, either orally or intraperitoneally, leads to a better incisional healing in terms of inflammation, granulation, collagen deposition, reepithelization and neovascularization., Conclusion: The present study supports the hypothesis that NAC administration alleviates the negative effects of radiotherapy on incisional wound healing by means of reducing oxidative stress markers and improving histologic parameters independent of the route of administration.

Purpose: In this study, we tested the effects of L-carnitine (LC) on radiation-induced ileal mucosal damage., Materials and Methods: Thirty Wistar albino rats were divided into five groups. The control group received physiological saline intraperitoneally (i.p.). Radiation-1 and radiation-2 groups received whole-body X-irradiation of 8.3 Gy as a single dose. These groups were sacrificed at the 6th hour and 4th day after irradiation, respectively. The Radiation-1 + LC and the radiation-2 + LC groups received the same dose irradiation plus a daily dose of 200 mg/kg LC. LC was applied one day before and for four days after irradiation., Results: The levels of serum monocyte chemotactic protein-1 (MCP-1) and interferon gamma (IFN-γ) were significantly higher in the radiation groups when compared with the control. Treatment with LC decreased the serum MCP-1 and IFN-γ levels considerably. In the radiations groups, the Chiu score was significantly elevated compared with that of the control group. However, LC administered prior to the irradiation reduced the severity of mucosal damage. The number of apoptotic cells of the ileal crypt in the irradiated rats increased from the 6th hour after irradiation and then decreased at 4th day., Conclusions: Our data demonstrated that LC may be beneficial to radiation enteritis.

Aim: The aim of the present study is to evaluate the possible protective effects of erythropoietin (EPO) on anastomotic wound healing after preoperative radiotherapy according to its pleiotropic mechanism of action., Methods: Thirty-two male Wistar albino rats were randomized into four groups containing eight rats each: ANAS group, standard resection plus anastomosis; RT+ANAS group, radiation plus standard resection plus anastomosis; ANAS+EPO group, standard resection plus anastomosis plus EPO; RT+ANAS+EPO, radiation plus standard resection plus anastomosis plus EPO. All animals were sacrificed by cardiac puncture, and anastomotic healing was measured by bursting pressure, hydroxyproline (OHP) levels, myeloperoxidase (MPO) activity and histopathological evaluations. Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) were also measured in serum specimens., Results: OHP levels in the RT+ANAS + EPO group were significantly increased compared with other groups (p < .05). In contrast, MPO activity in the RT+ANAS+EPO group was significantly decreased compared with other groups (p < .05). Serum MDA levels were found to be decreased in the ANAS+EPO and RT+ANAS+EPO groups (p < .05). Group comparisons demonstrated that bursting pressure was significantly higher in EPO treated rats (p < .05). The histopathology results revealed that EPO treatment improves anastomotic wound healing though decreased necrosis and inflammatory cell infiltration and increased fibroblast activity., Conclusion: The findings of the present study indicate that EPO contributes to wound healing and the strength of colon anastomosis following radiation due to its antioxidant and anti-inflammatory effects, but further studies are needed to explore the significance of these effects.

Background and Aims: The physiology of the patient during laparoscopy differs from that of open surgery. Both pneumoperitoneum and obstructive jaundice impair the hepatic function, but the combined insult has not been previously examined. In this study, we aimed to investigate the effects of carbon dioxide (CO(2)) pneumoperitoneum on hepatic function in a rat model of obstructive jaundice., Methods: Forty-four male Sprague-Dawley rats were divided into four groups: group 1 (n = 10), sham-operated group; group 2 (n = 12), obstructive jaundice group; group 3 (n = 10), CO(2) pneumoperitoneum group; and group 4 (n = 12), obstructive jaundice and CO(2) pneumoperitoneum group. Common bile duct was ligated and divided in the obstructive jaundice groups. After 6 days, a 12-mmHg pneumoperitoneum was induced, maintained for 60 min, and released for 120 min. Blood samples were drawn for the measurement of white blood cell and platelet counts, serum liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin). Tissue samples were obtained for analyses of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) levels. We evaluated the degree of liver injury on a grading scale from 0 to 4, histopathologically., Results: Pneumoperitoneum after biliary obstruction resulted in an increase in AST and ALT levels and a decrease in white blood cell and platelet counts. However, changes in liver tissue MDA, GSH, and SOD levels did not correlate with the changes in AST and ALT levels and white blood cell and platelet counts. After sham operation with pneumoperitoneum, the GSH levels in liver homogenate were significantly decreased in the group 3 when compared to the group 2. On the other hand, obstructive jaundice itself caused significant reduction in the SOD activity of liver homogenate in comparison to the group 3. Histopathologically, sinusoidal congestion and vacuolization were more severe in the group 3., Conclusions: Alterations in hepatic function occur in pneumoperitoneum applied jaundiced subjects. However, there were no statistically significant differences between the groups 2 and 4 with regard to white blood cell and platelet counts, serum liver enzymes including AST, ALT, and total bilirubin values, MDA and GSH levels and SOD activity of liver homogenate, and histologic damage. These results indicate that there is no additional risk on liver function associated with pneumoperitoneum performed in obstructive jaundice.

Ethanol causes oxidative stress and tissue damage. The aim of this study was to investigate the effect of antioxidant carnosine on the oxidative stress induced by ethanol in the rat brain tissue. Forty male rats were divided equally into four groups as control, carnosine (CAR), ethanol (EtOH), and ethanol plus carnosine (EtOH + CAR). Rats in the control group (n = 10) were injected intraperitoneally (i.p.) with 0.9% saline; EtOH group (n = 10) with 2 g/kg/day ethanol, CAR group (n = 10) received carnosine at a dose of 1 mg/kg/day and EtOH + CAR group (n = 10) received carnosine (orally) and ethanol (i.p.). All animals were sacrificed using ketamine and brain tissues were removed. Malondialdehyde (MDA), protein carbonyl (PCO) and tissue carnosine levels, and superoxide dismutase (SOD) activities were measured. Endogenous CAR levels in the rat brain tissue specimens were significantly increased in the CAR and EtOH groups when compared to the control animals. MDA and PCO levels in the EtOH group were significantly increased as compared to the other groups (P < 0.05). CAR treatment also decreased MDA levels in the CAR group as compared to the control group. Increased SOD activities were obtained in the EtOH + CAR group as compared to the control (P < 0.05). CAR levels in the rat brain were significantly increased in the CAR, EtOH and CAR + EtOH groups when compared to the control animals. These findings indicated that carnosine may appear as a protective agent against ethanol-induced brain damage.

Body weight loss is common in cancer patients, and is often associated with poor prognosis, it greatly impairs quality of life (QOL). Radiation therapy (RT) is used in head and neck cancers (HNC) either as a primary treatment or as an adjuvant therapy to surgery. Patients with HNC are most susceptible to malnutrition especially due to anorexia, which is aggravated by RT. Multiple pro-inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL-1beta), interferon (IFN)-gamma and tumor necrosis factor-alpha(TNF-alpha), have been all associated with the development of both anorexia and oral mucositis. Radiation-induced mucositis occurs in almost all patients, who are treated for HNC, it could also cause weight loss. Ghrelin is a novel 28-amino acid peptide, which up-regulates body weight through appetite control, increase food intake, down-regulate energy expenditure and induces adiposity. Furthermore, ghrelin inhibits pro-inflammatory cytokines such as IL-1alpha, IL-1beta, TNF-alpha which may cause oral mucositis and aneroxia, which are the results of weight loss. Thus weight loss during RT is an early indicator of nutritional decline, we propose that recombinant ghrelin used prophylactically could be useful as an appetite stimulant; and preventive of mucositis because of its anti-inflammatory effect, it might help patients maintain weight over the course of curative RT of the HNC and can improve specific aspects of QOL. This issue warrants further studies.