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Blocking of urotensin receptors as new target for treatment of carrageenan induced inflammation in rats

This study investigated possible role of U-II and its receptor expression in inflammation by using UTR agonist and antagonist in carrageenan induced acute inflammation. Rats were divided into 5 groups as (1) Healthy control, (2) Carrageenan control, (3) Carrageenan +Indomethacin 20mg/kg, orally, (4) Carrageenan +AC7954 (U-II receptor agonist, intraperitoneally) 30mg/kg and (5) Carrageenan +SB657510 (UTR antagonist, intraperitoneally) 30mg/kg. 1h after drug administration, carrageenan was injected. At the 3rd hour after carrageenan injection, agonist produced no effect while antagonist 63% anti-inflammatory effect respectively. UTR and UT-II expression increased in carrageenan induced paw tissue. Antagonist administration prevented the decrease in an antioxidant system and also capable to decrease TNF-α and IL-6 mRNA expressions. This study showed the role of urotensin II receptors in the physiopathogenesis of acute inflammatory response that underlying many diseases accompanied by inflammation.

Effects of amlodipine on ischaemia/reperfusion injury in the rat testis

The aim of this study was to examine the effects of amlodipine (AML) in rat testicular torsion/detorsion damage. In this study, rats were divided into eight groups: (i) sham; (ii) testicular ischaemia, 2 h of ischaemia; (iii) testicular ischaemia/reperfusion (I/R), 2 h of ischaemia followed by 2 h of reperfusion; (iv) ischaemia + AML (5 mg kg−1) administered 30 min before ischaemia; (v) ischaemia + AML (10 mg kg−1) administered 30 min before ischaemia; (vi) and (vii) I/R + AML (5 mg kg−1) and I/R + AML (10 mg kg−1) administered 1.5 h after the induction of ischaemia, respectively, and at the end of a 2‐h ischaemia period and a 2‐h reperfusion period applied; and (viii) sham + AML (10 mg kg−1). Significant decreases in levels of superoxide dismutase and glutathione were observed in ischaemia and reperfusion groups when compared with healthy controls. These antioxidant levels increased in AML groups while malondialdehyde levels significantly decreased. While increases in tumour necrosis factor‐alpha and transforming growth factor‐beta levels were found in the torsion and detorsion groups, significant decreases in the levels of these inflammatory cytokines were observed in the treatment groups. These results demonstrate that AML significantly produced protective effects on testis tissue damage that occurs in the torsion/detorsion model via biochemical, histopathological and molecular pathways.

Inhibiting renin angiotensin system in rate limiting step by aliskiren as a new approach for preventing indomethacin induced gastric ulcers.

PURPOSE Previously blocking the renin angiotensin system (RAAS) has been effective in the prevention of gastric damage. Therefore, the aim of this study was to investigate the effects of aliskiren, and thus, direct renin blockage, in indomethacin-induced gastric damage model. METHODS Effects of aliskiren were evaluated in indomethacin-induced gastric damage model on Albino Wistar rats. Effects of famotidine has been investigated as standard antiulcer agent. Stereological analyses for ulcer area determination, biochemical analyses for oxidative status determination and molecular analyses for tissue cytokine and cyclooxygenase determination were performed on stomach tissues. In addition, to clarify antiulcer effect mechanism of aliskiren pylorus ligation-induced gastric acid secretion model was applied on rats. RESULTS Aliskiren was able to inhibit indomethacin-induced ulcer formation. It also inhibited renin, and thus, decreased over-produced Angiotensin-II during ulcer formation. Aliskiren improved the oxidative status and cytokine profile of the stomach, which was most probably impaired by increased Angiotensin II concentration. Aliskiren also increased gastroprotective prostaglandin E2 concentration. Finally, aliskiren did not change the gastric acidity in pylorus ligation model. CONCLUSION Aliskiren exerted its protective effects on stomach tissue by decreasing inflammatory cytokines and oxidative stress as a result of inhibiting the RAAS, at a rate-limiting step, as well as its end product, angiotensin II. Aliskiren also significantly increased protective factors such as PGE2, but not affect aggressive factors such as gastric acidity.

Serum nesfatin-1 levels: a potential new biomarker in patients with subarachnoid hemorrhage*

Background: Acute subarachnoid hemorrhage (SAH) is a neurological emergency with significant potential for long-term morbidity and mortality. Nesfatin-1 is a polypeptide which is found in various regions of the brain that play role in the feeding and metabolic regulation. Objective: So this study aimed to investigate if nesfatin-1 levels in patients with SAH, could be used as a marker for the severity and prognosis. Method: Forty-eight consecutive patients (except those excluded) admitted to the emergency service of our hospital and hospitalized at our clinic with the diagnosis of aneurysmal SAH between 2011 and 2013 were included in the study and followed up for six months for outcome. The control group consisted of 48 healthy individuals of similar age and gender. Results: During the 6-month follow-up, 7 of 48 patients died and 16 (33.3%) patients had poor Glasgow Outcome Score (GOS) scores. In the study group, the mean nesfatin-1 level was significantly higher than the control group (7.36 ± 2.5 pg/ml and 4.29 ± 2.02 pg/ml, respectively; p < 0.01). The mean nesfatin-1 level was 11.58 ± 0.87 pg/ml in the non-survival group and 6.64 ± 1.89 pg/ml in the survival group. Furthermore, it was 10.22 ± 1.42 pg/ml in patients with poor outcome in terms of GOS and 5.93 ± 1.46 pg/ml in those with good outcome. The nesfatin-1 levels significantly increased with worsening of GOS, the World Federation of Neurological Surgeons grading system, and Fisher scores and increasing plasma C-reactive protein levels (p < 0.01 for all). Conclusion: The present study is the first that shows the mortality/poor outcome of the SAH with assessing serum nesfatin-1 levels. So levels of nesfatin-1 might be useful in SAH management.

Effects of oral zinc administration on long-term ipsilateral and contralateral testes damage after experimental testis ischaemia-reperfusion.

The purpose of this study was to examine potential long‐term post‐torsion changes that can occur in the histopathology, biochemistry and spermatogenesis of both torsioned and nontorsioned opposite testes. The study also determines the effect of zinc (Zn) administration on the testicular torsion/detorsion (T/D) damage on both testes. Forty‐eight male rats, divided equally into eight groups: (SHAM), (SHAM+,Zn+), (T/D+, Zn− 1 month), (T/D+,Zn− 2 months), (T/D+,Zn− 3 months), (T/D+,Zn+ 1 months), (T/D+,Zn+ 2 months), (T/D+,Zn+ 3 months), have been used. Drug administration was carried out by adding 100 μg (0.016 ml/rat) Zn per rat to drinking water in related groups. Testicular damage decreased superoxide dismutase (SOD) and glutathione (GSH) and increased malondialdehyde (MDA) in the testis tissues of rats, while Zn administration increased SOD and GSH and decreased MDA in the testis tissues in comparison with the SHAM group. The beneficial effect of zinc sulphate was more evident on the nonrotated testis than the rotated testis. In the histopathological study, a significant decrease in torsion and detorsion injuries was observed in the treatment groups compared to the torsion and detorsion groups. We found a protective effect of zinc sulphate on oxidative stress as a result of T/D injuries in rats, especially for the nonrotated testis; results were supported histopathologically.

A novel approach to contrast-induced nephrotoxicity: the melatonergic agent agomelatine

OBJECTIVE To study the potential nephroprotective role of agomelatine in rat renal tissue in cases of contrast-induced nephrotoxicity (CIN). The drugs action on the antioxidant system and proinflammatory cytokines, superoxide dismutase (SOD) activity, levels of glutathione (GSH) and malondialdehyde (MDA) and the gene expression of interleukin-6 (IL-6), tumour necrosis factor (TNF)-α and nuclear factor kappa B (NF-κB) was measured. Tubular necrosis and hyaline and haemorrhagic casts were also histopathologically evaluated. METHODS The institutional ethics and local animal care committees approved the study. Eight groups of six rats were put on the following drug regimens: Group 1: healthy controls, Group 2: GLY (glycerol), Group 3: CM (contrast media--iohexol 10 ml kg(-1)), Group 4: GLY+CM, Group 5: CM+AGO20 (agomelatine 20 mg kg(-1)), Group 6: GLY+CM+AGO20, Group 7: CM+AGO40 (agomelatine 40 mg kg(-1)) and Group 8: GLY+CM+AGO40. The groups were evaluated by one-way analysis of variance and Duncans multiple comparison test. RESULTS Agomelatine administration significantly improved the serum levels of blood urea nitrogen (BUN) and creatinine, SOD activity, GSH and MDA. The use of agomelatine had substantial downregulatory consequences on TNF-α, NF-κB and IL-6 messenger RNA levels. Mild-to-severe hyaline and haemorrhagic casts and tubular necrosis were observed in all groups, except in the healthy group. The histopathological scores were better in the agomelatine treatment groups. CONCLUSION Agomelatine has nephroprotective effects against CIN in rats. This effect can be attributed to its properties of reducing oxidative stress and inhibiting the secretion of proinflammatory cytokines (NF-κB, TNF-α and IL-6). ADVANCES IN KNOWLEDGE CIN is one of the most important adverse effects of radiological procedures. Renal failure, diabetes, malignancy, old age and non-steroidal anti-inflammatory drug use pose the risk of CIN in patients. Several clinical studies have investigated ways to avoid CIN. Theophylline/aminophylline, statins, ascorbic acid and iloprost have been suggested for this purpose. Agomelatine is one of the melatonin ligands and is used for affective disorders and has antioxidant features. In this study, we hypothesized that agomelatine could have nephroprotective, antioxidant and anti-inflammatory effects against CIN in rats.

Is there any correlation between levels of serum ostepontin, CEA, and FDG uptake in lung cancer patients with bone metastasis?

OBJECTIVE In this study, an evaluation was made of the relationship between the serum levels of carcinoembryonic antigen (CEA), osteopontin (OPN), and the semi-quantitative parameters of 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in lung cancer patients with bone metastasis. MATERIAL AND METHODS The evaluation included 42 non-small cell lung cancer (NSCLC) and 31 small cell lung cancer (SCLC) patients who were referred to our institution for staging by (18)F-FDG PET/CT. The biochemical parameters measured included CEA and OPN serum levels. RESULTS Serum levels of OPN in NSCLC patients with and without bone metastasis were 21.20±4.97 ng/ml and 13.33±4.53 ng/ml, respectively (p<0.05). In SCLC patients with and without bone metastasis serum OPN levels were 23.95±4.78 ng/ml and 17.30±3.09 ng/ml, respectively (p<0.05). Serum levels of CEA in NSCLC patients with and without bone metastasis were 33.79±6.49 ng/ml and 11.74±2.96 ng/ml, respectively (p<0.05). In SCLC patients with and without bone metastasis serum levels of CEA were 28.93±4.59 ng/ml and 13.88±4.47 ng/ml, respectively (p<0.05). There were no correlations between primary tumor SUVmax, and serum levels of CEA and OPN. CONCLUSIONS Bone metastasis can be detected in patients with lung cancer by measuring CEA and OPN levels. Increased levels of CEA and OPN levels may be considered an early warning sign in patients needing accurate imaging, as they are at higher risk of bone metastasis.