Cengiz Koçak

Molecular and biochemical evidence on the protective effects of embelin and carnosic acid in isoproterenol-induced acute myocardial injury in rats

AIMS Acute myocardial infarction is a serious acute cardiac disorder and heart disease is still a major public health problem in adults. We investigated the effects of embelin (EMB) and carnosic acid (CA) in animals with isoproterenol (ISO)-induced myocardial injury. MAIN METHODS Adult male Wistar-Albino rats were divided into four groups: control, ISO, ISO with EMB, and ISO with CA. Before myocardial injury was induced, drugs were administered by oral gavage. Myocardial injury was induced by subcutaneous injection of ISO hydrochloride for 2 consecutive days. Serum cardiac troponin I (cTnI), ischemia modified albumin (IMA), heart fatty acid binding protein (HFABP) levels and paraoxonase-1 (PON-1) activity, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), tumor necrosis factor-α (TNF-α) levels, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-Px) activity were measured. Tissue mRNA expression levels of nuclear factor-kappa B (NF-κB), P38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor erythroid 2-related factor 2 (Nrf2) were analyzed. In addition, cardiac tissues were evaluated histopathologically and immunohistochemically. KEY FINDINGS All tested compounds reduced myocardial damage, apoptosis, cTnI, IMA, HFABP, TOS, and TNF-α levels, NF-κB, p38 MAPK, and phosphorylated c-Jun N-terminal protein kinase (pJNK 1/2) expressions. All tested compounds increased SOD activity, GSH-Px activity, TAS levels, TT levels, phosphorylated extracellular signal-regulated kinase (pERK 1/2), and Nrf2 expressions. SIGNIFICANCE Our results suggest that EMB and CA pretreatment could reduce myocardial injury via antiinflammatory, antioxidant, and antiapoptotic effects.

Protective effects of simvastatin administered in the experimental hepatic ischemia-reperfusion injury rat model

BACKGROUND Hepatic ischemia-reperfusion (I/R) injury is a major complication in clinical practice. Previous studies suggest that statins have pleiotropic effects in addition to cholesterol-lowering effects. In this study, we aimed to investigate the hepatoprotective role of two different doses of simvastatin (SV) pretreatment in rats with experimental hepatic I/R injury. METHODS Adult male Sprague-Dawley rats were divided into four groups (n = 7 in each group) :control, I/R, I/R with 2.5-mg/kg SV, and I/R with 5.0-mg/kg SV. Before hepatic I/R was induced, SV was injected intraperitoneally at doses of 2.5 and 5.0 mg/kg. After 45-min ischemia and a 60-min reperfusion period, the animals were euthanized, and liver tissues were excised. Tissue levels of malondialdehyde and nitric oxide, and activities of superoxide dismutase, glutathione peroxidase, and catalase were measured. Liver tissues were also evaluated histopathologically and immunohistochemically. RESULTS Histopathologic evaluation showed that 5.0-mg/kg SV reduced hepatic damage and apoptosis. Pretreatment with 5.0-mg/kg SV reduced malondialdehyde and nitric oxide levels (P < 0.01) and increased superoxide dismutase, glutathione peroxidase, and catalase activities significantly (P < 0.001, P < 0.01) in I/R with 2.5-mg/kg SV compared with I/R group. In addition, SV decreased Kupffer cell activation, and hypoxia-inducible factor-1α and vascular endothelial growth factor protein levels. CONCLUSIONS The results of this study suggest that 5.0-mg/kg SV pretreatment may be protective against hepatic I/R injury. This effect can be achieved by antioxidant and antiapoptotic activities.

Antiadhesive and anti-inflammatory effects of pirfenidone in postoperative intra-abdominal adhesion in an experimental rat model

BACKGROUND Pirfenidone (PF) is a potent antifibrotic and anti-inflammatory agent. We investigated the protective effect of PF against postoperative intra-abdominal adhesions. MATERIAL AND METHODS Thirty male Sprague-Dawley rats were divided into three groups (n = 10 in each group). In group 1 (control), adhesion induction was performed by cecal abrasion, and no treatment was administered. In group 2 (vehicle), for 2 wk after adhesion induction, 0.4%-carboxymethylcellulose was administered by gavage. In group 3 (PF treatment), for 2 wk after adhesion induction, 500-mg/kg/d PF was administered by gavage. On the 15th postoperative day, the animals were killed, and cecal and peritoneal tissues were excised. The adhesions were graded macroscopically. The protein concentrations and mRNA expression levels of the following genes were measured in the tissues: matrix metallopeptidase-9 (MMP-9); tissue inhibitor of metalloproteinase-1 (TIMP-1); tumor necrosis factor-alpha (TNF-α); and transforming growth factor-beta 1 (TGF-β1). The tissue samples were also evaluated histopathologically. RESULTS Macroscopic and histopathologic evaluation showed that PF-reduced adhesion and inflammation (P < 0.001, P = 0.004, respectively). Pretreatment with PF-reduced TIMP-1, TNF-α, and TGF-β1 protein concentrations (P < 0.001, P < 0.001, and P < 0.001, respectively) and mRNA expression levels (P = 0.030, P = 0.005, and P = 0.016, respectively) and increased MMP-9 protein concentrations (P < 0.001) and mRNA expression (P = 0.021). CONCLUSIONS The findings of this study suggest that PF can be used as a protective agent to prevent the development of peritoneal adhesions and inflammation during the postoperative period.

Micro RNA-320 as a novel potential biomarker in renal ischemia reperfusion

Abstract Aim: MicroRNAs (miR) are important diagnostic and treatment targets due to their different tissue expressions and their central position in the regulation of gene expressions. miR studies might pioneer emerging of new diagnostic tools and treatment goals in kidney diseases. Captopril (CAP) and telmisartan (TEL) were shown to be effective in ischemia reperfusion (IR) injury. There is not any study about the effect of TEL and CAP over miR-21-320-146a. Our aim was to study the effects of CAP and TEL over miR on renal IR model. Methods: We used 12–16 weeks-old Wistar-Albino rats that weigh 300–350 g. Rats (n, 6) were randomized into four groups (Control, IR, IR + CAP, IR + TEL). Urea, creatinine, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), super oxide dismutase (SOD), and miRs were analyzed. Results: Urea, creatinine, TOS, OSI levels of IR + CAP, and IR + TEL groups were lower comparing to IR group. TAS and SOD levels were higher in IR group than IR + TEL group. miR-21-320-146a showed increase in renal IR injury. miR-320, 146a showed significant decrease in IR + CAP and IR + TEL groups comparing to IR group. We showed histopathological recovery and decreased apoptosis in IR + CAP and IR + T groups than IR group. Conclusion: We, for the first time in the literature, showed that miR-320 is increased in IR injury. miR-320 might be a novel diagnosis and treatment target in renal ischemic reperfusion injury. Also, for the first time, we showed that CAP and TEL cause functional and histopathological recovery and lower miR-146a and miR-320.

Effects of captopril, telmisartan and bardoxolone methyl (CDDO-Me) in ischemia-reperfusion-induced acute kidney injury in rats: an experimental comparative study.

Renal ischemia‐reperfusion (IR) injury is one of the most common causes of acute kidney injury. This study investigated the effects of captopril (CAP), telmisartan (TEL) and bardoxolone methyl (BM) in animals with renal IR injury. Adult male Wistar–Albino rats were divided into six groups: control, vehicle, IR, IR with CAP, IR with TEL and IR with BM. Before IR was induced, drugs were administered by oral gavage. After a 60‐min ischemia and a 120‐min reperfusion period, bilateral nephrectomies were performed. Serum urea, creatinine, neutrophil gelatinase‐associated lipocalin (NGAL) levels, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), asymmetric dimethylarginine (ADMA) levels, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH‐Px) activity were measured. Tissue mRNA expression levels of peroxisome proliferator‐activated receptor‐ɣ (PPAR‐ɣ), nuclear factor erythroid 2‐related factor 2 (Nrf2) and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) were analyzed. In addition, renal tissues were evaluated histopathologically and immunohistochemically. All tested drugs reduced renal damage, apoptosis, urea, creatinine, NGAL, TOS, nitric oxide (NO) and ADMA levels, NF‐κB, inducible nitric oxide synthase (iNOS) and endothelin‐1 (ET‐1) expressions (P < 0.001). All tested drugs increased SOD activity, GSH‐Px activity, TAS levels, TT levels, endothelial nitric oxide synthase (eNOS) expression, dimethylarginine dimethylaminohydrolases (DDAHs) expression, Nrf2 expression and PPAR‐ɣ expression (P < 0.001, P < 0.003). These results suggest that CAP, TEL and BM pretreatment could reduce renal IR injury via anti‐inflammatory, antioxidant and anti‐apoptotic effects.

The neutrophil-to-lymphocyte ratio as a diagnostic marker for malignant thyroid diseases

Abstract Background: The neutrophil-lymphocyte ratio (NLR) is a good marker of malignant diseases. The aim of this study was to investigate NLR as a diagnostic marker of thyroid cancer in patients with malignant thyroid diseases compared to those with benign thyroid diseases. Methods: Two hundred and fifty three patients were divided into two groups: benign and malignant thyroid disease patients. Malignant thyroid disease group was not sub-grouped further into differentiated and undifferentiated. The preoperative complete blood count and biochemical parameters, including NLR, were evaluated. Results: The mean neutrophil count was found to be significantly higher, whereas the mean lymphocyte count was found to be significantly lower in the malignant group which includes 40 of the patients. As a result, NLR was significantly higher in the malignant group than in the benign group (p<0.001). Conclusion: This is the first study to show the value of NLR as a marker for malignant thyroid diseases including all subtypes.

DOES NEUTROPHIL TO LYMPHOCYTE RATIO PREDICT HOSPITAL STAY IN APPENDECTOMY PATIENTS

BACKGROUND We aimed to investigate the relationship between the neutrophil to lymphocyte ratio (NLR) and postoperative length of hospital stay. In addition, the impact of radiological and histopathological findings on hospital stay was also evaluated. METHOD This is a retrospective study. One hundred three patients with appendicitis were in-cluded. The diagnosis was confirmed by computed tomography (CT), ultrasonography and histopathological examination. Correlations between the length of hospital stay and age, gender, NLR, c-reactive peptide levels (CRP), the appendix diameter on CT or ultrasonogra-phy, appendix localisation and pathology reports were evaluated. RESULTS The length of hospital stay was not related to age or gender. The length of hospital stay after appendectomy was correlated with appendix diameter on CT and phlegmonous appendicitis, but it was not associated with NLR, CRP levels or the appendix diameter on ultrasonography. CONCLUSION To our knowledge, this is the first comprehensive study to evaluate the associa-tion between NLR levels and the length of hospital stay in patients with acute appendicitis. The NLR was not found to be associated with the length of hospital stay. The appendix di-ameter on CT and appendix pathology reports were correlated with the length of postopera-tive hospital stay in appendectomy patients.

Carcinosarcoma of the Thyroid Gland

Introduction. Surgeon has significant role in the management of such rare and controversial clinical entities related to thyroid gland. In this case report we have presented an elderly patient with rapid enlargement in thyroid that was related to carcinosarcoma. Case Presentation. A 60-year-old lady was presented with rapid enlargement of the thyroid gland. A fine needle aspiration of the nodule in right lobe was performed several weeks before presentation to our clinic. End diagnosis was a papillary carcinoma of the thyroid with spindle cell component. Thus the nodule was recognized to be a carcinosarcoma. Conclusion. Thyroid surgery merits a multidisciplinary approach. Indeed the surgeon should make a conclusive decision in some controversial and rare clinical entities such as carcinosarcoma.

Antioxidant Effect of Ukrain Versus N-Acetylcysteine Against Acute Biliary Pancreatitis in An Experimental Rat Model

ABSTRACT Purpose/Aim: Oxidative stress plays an important role in the pathogenesis of acute pancreatitis (AP). We compared the therapeutic effects of Ukrain (NSC 631570) and N-acetylcysteine (NAC) in rats with AP. Materials and Methods: Forty male Sprague Dawley rats were divided into four groups: controls; AP; AP with NAC; and AP with Ukrain. AP was induced via the ligation of the bile–pancreatic duct; drugs were administered intraperitoneally (i.p.) 30 min and 12 h after AP induction. Twenty-four hours after AP induction, animals were sacrificed and the pancreas was excised. Levels of malondialdehyde (MDA) and nitric oxide (NO), and activity levels of tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO) were measured in tissue samples. Total oxidant status (TOS), total antioxidant status (TAS), and total bilirubin, as well as activity levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase and lipase were measured in serum samples. Pancreatic tissue histopathology was also evaluated. Results: Test drugs reduced levels of MDA, NO, TNF-α, total bilirubin, AST, ALT, TOS and MPO, amylase and lipase activities (P < 0.001), and increased TAS (P < 0.001). Rats treated with test drugs attenuated AP-induced morphologic changes and decreased pancreatic damage scores compared with the AP group (P < 0.05). Both test drugs attenuated pancreatic damage, but the therapeutic effect was more pronounced in rats that received Ukrain than in those receiving NAC. Conclusions: These results suggest that treatment with Ukrain or NAC can reduce pancreatic damage via anti-inflammatory and antioxidant effects.

Incidental signet ring cell carcinoma of the gallbladder in routine histopathology

Cholecystectomy is a common surgical procedure for various indications. Preoperative imaging is the main stay in the management of the patients. Routine and/or selective histopathological examination of the cholecystectomy materials have been discussed previously. However, incidental findings may be only observed with routine histopathological examination. Here, we report an incidental gallbladder signet cell carcinoma in a 66 years old patient. This case underlines the importance of routine histopathological examination after cholecystectomy.