Introduction: The presence of weaknesses in the efficacy of endogenous natriuretic and vasodilator agents plays a significant role in developing high blood pressure. It is often suggested that oxidative stress is critical in developing hypertension due to nitric oxide synthase (NOS) inhibition. This study aimed to investigate the intrarenal dopaminergic system activities, involvement of oxidative stress, and blood pressure changes resulting from NOS inhibition with N-nitro-L-arginine (L-NNA) and/or L-buthionine sulfoximine (BSO). Methods: Male Wistar albino rats (n = 24) were administered water containing 50 mg/L L-NNA for 21 days and/or intraperitoneal injections of BSO (125 mg/kg twice daily) for seven days; control rats were administered tap water. The rats' blood pressure; water and salt balance; total oxidant and antioxidant capacities; and urinary dopamine, adrenaline, and noradrenaline levels were measured. Results: While L-NNA and BSO alone did not significantly alter blood pressure, their coadministration caused rats to develop hypertension and significantly reduced the fractional excretion of sodium, increasing its tubular reabsorption. Urinary dopamine levels, indicators of intrarenal dopamine synthesis, did not change significantly. Conclusion: These results indicate the importance of the weakness of endogenous natriuretic systems such as nitric oxide in hypertension development. While BSO did not induce oxidative stress in the measured parameters, it was shown for the first time as an actor in hypertension development in subjects with NOS inhibition to the extent that such inhibition did not increase blood pressure.

This research study was conducted to investigate the cardioprotective activity of alcoholic extract of Ganoderma lucidum (GL) against cyclophosphamide (CYP)-induced cardiotoxicity in rats model. Therewithal, the regulation in the expression level of Aquaporin (AQP) water channels in the heart was evaluated. Cardiotoxicity was induced in Wistar rats by administering a single-dose injection of CYP (200 mg/kg, i.p.) on the seventh day of the experimental period. GL (500 mg/kg, gavage) was administered daily for seven days. Cardiac alteration following CYP and GL administration was evaluated using electrocardiographic changes, morphological staining, AQP gene expression and western blot analysis. It was observed that the CYP administration significantly (p < 0.001) increased cardiac troponin- I (cTn-I) and elevated the level of creatine kinase isoenzyme MB (CK-MB). Further, rats treated with CYP showed increased expression levels of AQP-3, -4 and − 7 compared to the control group. The treatment with GL significantly (p < 0.001) reversed the level of cardiac biomarkers in CYP-induced cardiotoxicity. Potential cardioprotective effect of GL which reduced the severity of cellular damage of the myocardium was supported by histopathological examination. The biochemical, expressional and histopathological reports supported the cardioprotective activity of GL which could be attributed to changes in myocardial edema. To the best knowledge of the authors, this is the first study that reports the cardioprotective role of GL in CYP-induced myocardial edema and the changes in the expression levels of AQP.

CP is one of the most widely used antineoplastic agents. However, its clinical application is very limited due to its severe toxic effects. The present study aimed to reveal the effects of NAC, which exhibits broad biological activities in reducing CP-induced liver damage, in consideration of biochemical, genetic, and histopathological findings. Twenty-eight wistar rats were randomly divided into four groups of seven animals. A dose of saline was administered (i.p.) to the control group for 5 days. One dose of NAC (200 mg/kg) was administered to the NAC group for 5 days (i.p.). To the NAC + CP group, a dose of CP (7.5 mg/kg) was administered on days 2 and 5 of the experiment, a dose of NAC (200 mg/ kg) (i.p.) was administered for 5 day of the experiment. CP (7.5 mg/kg) was administered to the CP group on days 2 and 5 of the experiment. At the end of the experiment, the biochemical, histological, and mRNA expression analyses of the liver tissues isolated from all the rats were performed. A statistically significant decrease was observed in the AST and ALT enzyme activities in Group NAC + CP compared to Control and CP groups. In addition, it was determined that the NAC administration reduced CP-induced inflammation by increasing the level of NF-κB and decreased CP-caused oxidative stress by decreasing the GPx level. Moreover, the histopathological analyses showed that NAC improved liver morphology. It was revealed by Western blotting analysis that NAC promoted Bcl-2 signaling and decreased p53 signaling. The findings herein showed that NAC could help alleviate hepatotoxicity, a serious therapeutic complication, by reducing CP-induced oxidative stress and playing an effective part in the regulation of apoptotic markers.

Preservation of the brain is important to reducing recurrent seizures and other neurological sequelae after status epilepticus (SE). Medical ozone (MedO3) shows antioxidant, anti-inflammatory and anti-apoptotic properties in the human body. In this study, it was aimed to understand the neuroprotective potential of MedO3 in the acute period after SE. Mature rats of Wistar Albino were used for the study. Group design O3 + SE: SE induced after MedO3, O3: MedO3 alone was given, SE: SE only induced, SE + O3; MedO3 given after SE, C: control and S: sham control group. SE was induced with lithium-pilocarpine experimental model and evaluated on the Racine scale. Peripheral blood samples and brain tissue samples were taken before decapitation. Histopathological evaluation of the hippocampus of the rats given medical O3 before and after SE were studied. The highest peripheral blood oxidative stress index (OSI) was found in SE group. The OSI level in O3 + SE and SE + O3 was significantly higher than SE/C/S. Gene expressions of TNF-α and IL-1β mRNA were significantly higher in SE compared to other groups. Histopathologically; eosinophilia, cellular shrinkage and interstitial oedema were detected in the most severe SE and to a lesser extent in O3 + SE/ SE + O3. MedO3 reduced SE-induced oxidative damage, neuroinflammation and neuronal injury and contributed positively to neuroprotection.

Purpose: Status epilepticus (SE) is a highly common neurological disease in children, with recurrent generalized convulsions for more than 30 minutes, and when not controlled, neuronal damage occurs in the brain. The aim of this study was to evaluate the changes in KCNQ1 and KCNQ3 gene expression levels in the acute period after SE. Materials and Methods: In rats, an experimental SE model was created with Li-Pc. Study; female Wistar albino [250-350 g, 21 (n=7)] rats were used in 3 groups as SE, control and sham groups. The total RNA obtained from brain tissues was converted to cDNA, and gene expression levels of KCNQ1 and KCNQ3 genes were assessed by quantitative real-time PCR (qRT-PCR) method. Results: Statistically in SE group; compared to the control and sham groups, a significant difference was observed in the gene expression levels of the KCNQ1 and KCNQ3 ion channels. The KCNQ1 and KCNQ3 gene expression levels of the experimental group was found higher than the other groups. Conclusion: Determining the changes in mRNA expression levels of genes encoding K+ ion channels will help to better understand the pathological mechanisms that occur during epilepsy. In the SE experimental model created, it is believed that an increase in mRNA expression of KCNQ1 and KCNQ3 will lead to drug therapy studies planned for the future.

Aim: The aim of this study is to investigate the supplemental effect of oleuropein which is the most commonly used corticosteroid in AR (Allergic rhinitis) treatment and to evaluate possible inflammatory-reducing properties in the liver. Material and Methods: The study was carried out on 42 male Wistar rats. The animals were randomly divided into 6 groups including G1 (C), G2 (AR), G3 (AR +SF), G4 (AR+MF), G5 (AR+OLE), G6 (AR+OLE+MF). Tumor necrosis factor-alpha (TNF-alpha) and Interleukin-1 beta (IL-1 beta) gene expression levels were assessed by RT-PCR analysis in liver tissues. In addition, liver tissues were evaluated histopathologically as a result of hematoxylin eosin (H&E) staining. Results: TNF-alpha and IL-1 beta gene expression levels in liver tissues were compared between groups and the results were statistically significant in all groups (p<0.000). Histopathological evaluation in H&E sections, sinusoidal dilatation, and hydropic degeneration were not observed in the liver tissue architecture of G1 (C). As a result of the examination of the sections belonging to G2 (AR), the location of hepatocyte cords and minimal destruction in portal areas were observed in organ architecture, and intensive sinusoidal dilatation was observed. Sinusoidal dilation was advanced in G3 (AR+SF). In addition, swelling and moderate hydropic degeneration were observed in hepatocytes, and focal lytic necrosis areas were not observed in G3 (AR+SF). All groups in terms of sinusoidal dilation and hydropic degeneration were significant differences statistically (p=0.000;0.001). Discussion: The present data indicated that oleuropein treatment suppresses inflammation in liver tissue caused by AR and it has no side effect in the experimental AR model. Oleuropein can be used as an auxiliary agent in the treatment of routine AR.

Öz Purpose: Status epilepticus (SE) is a highly common neurological disease in children, with recurrent generalized convulsions for more than 30 minutes, and when not controlled, neuronal damage occurs in the brain. The aim of this study was to evaluate the changes in KCNQ1 and KCNQ3 gene expression levels in the acute period after SE. Materials and Methods: In rats, an experimental SE model was created with Li-Pc. Study; female Wistar albino [250–350 g, 21 (n=7)] rats were used in 3 groups as SE, control and sham groups. The total RNA obtained from brain tissues was converted to cDNA, and gene expression levels of KCNQ1 and KCNQ3 genes were assessed by quantitative real-time PCR (qRT-PCR) method. Results: Statistically in SE group; compared to the control and sham groups, a significant difference was observed in the gene expression levels of the KCNQ1 and KCNQ3 ion channels. The KCNQ1 and KCNQ3 gene expression levels of the experimental group was found higher than the other groups. Conclusion: Determining the changes in mRNA expression levels of genes encoding K+ ion channels will help to better understand the pathological mechanisms that occur during epilepsy. In the SE experimental model created, it is believed that an increase in mRNA expression of KCNQ1 and KCNQ3 will lead to drug therapy studies planned for the future. Amaç: Status epileptikus (SE) 30 dakikadan daha uzun süre tekrarlayan jeneralize konvulziyonlarla birlikte çocuklarda oldukça yaygın bir şekilde görülen nörolojik bir hastalıktır ve kontrol edilmediğinde, beyinde nöronal hasarlar meydana gelir. Bu çalışmanın amacı SE sonrası akut dönemde KCNQ1 ve KCNQ3 gen ekspresyon seviyelerindeki değişiklikleri değerlendirmektir. Gereç ve Yöntem: Sıçanlarda Li-Pc ile deneysel SE modeli oluşturuldu. Çalışmada; SE, kontrol ve sham grupları olmak üzere 3 grupta dişi Wistar albino [250–350 gr, 21 adet (n=7)] sıçan kullanıldı. Beyin dokularından elde edilen total RNA, cDNA'ya çevrilerek KCNQ1 ve KCNQ3 genlerinin kantitatif gerçek zamanlı PCR (qRTPCR) yöntemi ile gen ekspresyon değişimleri değerlendirildi. Bulgular: İstatistiksel olarak SE grubunda; kontrol ve sham grubuna kıyasla KCNQ1 ve KCNQ3 genlerinin ekspresyon seviyelerinde anlamlı oranda farklılık görüldü. Deney grubunun KCNQ1 ve KCNQ3 gen ekspresyon düzeyleri diğer gruplardan yüksek bulundu. Sonuç: K+ iyon kanallarını kodlayan genlerin mRNA ekspresyon seviyelerindeki değişikliklerin belirlenmesi epilepsi sırasında oluşan patolojik mekanizmaların daha iyi anlaşılmasına yardımcı olacaktır. Oluşturulan SE deneysel modelde KCNQ1 ve KCNQ3 mRNA ekpresyonlarında artış saptanması ileride yapılması planlanan tedaviye yönelik ilaç çalışmalarına yol göstereceğine inanılmaktadır.

Valproic acid (VPA) is a anticonvulsant and mood-stabilizing agent used to treat epilepsy in patients of all ages. However, it can cause hepatotoxicity with increased oxidative stress. Melatonin (MEL) is known as antioxidant and antiinflammatory agent. Therefore, the present study designed to investigate the probable protective role of melatonin against VPA-induced liver toxicity. For that purpose, 28 Wistar rats were randomly selected and divided into four groups, namely the Group C (vehicle), VPA (500 mg/kg/day VPA), MEL + VPA (10 mg/kg/day melatonin + 500 mg/kg/day VPA) and MEL (10 mg/kg/day melatonin). The agents were given by oral gavage for 14 days. Blood and liver tissue samples from all the rats were harvested on the 15th day of experiment. Biochemical analyses were conducted on the blood samples. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), alpha glutathione S-transferases (α-GST), nuclear factor-κB (NF-κB), myeloperoxidase (MPO) and changes in gene expression were examined in the liver tissues. Also, liver histopathological analyses were conducted. VPA administration significantly increased the levels of α-GST, MDA, NF-κB and of IL-1β, TNF-α gene expression in the liver compared to Group C. Moreover, vacuolization, hydropic degeneration, inflammatory cell infiltration, and sinusoidal congestion were commonly detected in the VPA-treated group along with the highest apoptotic index (TUNEL staining) values. Melatonin administration was revealed to exhibit powerful protective properties at cellular, inflammatory and oxidative level activities against VPA-induced liver toxicity. Therefore, melatonin administration may be used as an adjuvant therapy against to VPA-induced liver toxicity.

Chromatography has been preferred in the medical field as one of the most important analytical methods used for the identification and quantification of a drug and its metabolites in recent years. Various chromatographic techniques have been developed to differentiate drugs according to their characteristics and interaction types. Among these techniques, particularly High Performance Affinity Chromatography (HPAC), Cell Membrane Chromatography (CMC), Mixed Mode Chromatography (MMC), High Performance Liquid Chromatography (HPLC) are used for pharmaceutical purposes for bioanalysis of drugs in preclinical and clinical studies. The success of Chromatography in the development of rapid and precise analytical methods provides superior specificity and sensitivity in the research of pharmacokinetic properties of drugs in R&D. In personalized medicine, it is important how the dosage and effect of drugs varies from person to person. In recent years, chromotography has been preferred as a promising technique in the analysis of drug-protein binding and in the examination of clinical or pharmaceutical samples.

Yöntem: Bu çalışma, Ağustos 2013 Kasım 2013 tarihleri arasında Çanakkale Onsekiz Mart Üniversitesi Sağlık Uygulama ve Araştırma Hastanesi Fizik Tedavi ve Rehabilitasyon Polikliniğinde gerçekleştirilmiştir. 42 AS hastası ve 58 sağlıklı kontrol BMP-6 (rs267192 ve rs267196) polimorfizmi için ters transkripsiyonpolimeraz zincir reaksiyonu (RT-PCR) analizi ile kontrol edilmiştir. Klinik veriler olarak yaş, cinsiyet, vücut kitle indeksi, C-reaktif protein (CRP), eritrosit sedimantasyon hızı, bath ankilozan spondilit hastalık aktivite indeksi (BASDAI) ve HLA-27 pozitifliği araştırılmıştır. BMP-6 polimorfizmi ile laboratuvar bulguları arasındaki ilişki değerlendirilmiştir.

Kemik morfogenetik proteinlerinin (BMP'ler) çeşitli popülasyonlarda ankilozan spondilit (AS) ile ilişkili olduğu bildirilmiştir.Bu çalışmanın amacı, (BMP-6) gen polimorfizminin (rs267192 ve rs267196) AS ile ilişkisini belirlemek ve aralarındaki ilişkileri klinik ve laboratuvar verilerine dayanarak değerlendirmektir.

Cytokines are multifunctional polypeptides synthesized by different body cells. They have clinical significance in terms of disease diagnosis, treatment and prevention. Cytokines TNF-α and IL-6 play an important role in the growth and differentiation of cells.Vascular Endothelial Growth Factor (VEGF) is excessively produced in epithelial, mesenchymal, and particularly in tumor cells. Studies have shown that the increased serum concentrations of IL-6, TNF-α, VEGF are strongly associated with colorectal cancer and directly with the clinical stage of the disease. This can be used to diagnose cancer and to identify patients with a bad prognosis who can avail themselves of a more aggressive treatment. The present study investigated the role of cytokines in the development of cancer by comparing preoperative serum cytokine levels of patients suffering from colorectal cancer with those of the healthy control group. The prognostic significance of the data obtained has also been evaluated. For this purpose, IL-6, TNF-α and VEGF levels in 60 serums, 30 preoperatively taken from patients with colorectal cancer and 30 from a healthy control group at í‡anakkale Onsekiz Mart University General Surgery Clinic, were determined by ELISA kits. The statistical analyses of the obtained data were evaluated on SPSS, a statistical package program. In this study, no significant difference was obtained between the mean scores concerning the IL-6 and VEGF serums of the colorectal cancer and healthy group (p>.05). But a statistically significant decrease was observed in the TNF-α serum level of the colorectal cancer group in comparison with the control group (p= .016; p < .05).

Classical techniques employed to determine the amount of extractable poly(hydroxyalkanoate)s (PHAs) from cells, are laborious and destructive. Sudan black staining is commonly used in the laboratory to investigate the presence of intracellular PHA. The aim of the present study was to develop a low-cost alternative technique to achieve a quick determination of extractable intracellular PHA. This methodology employs a basic laboratory spectroscopy equipment and Sudan black dye for spectra determination. The correlation between the content of PHA in cell samples taken directly from the culture flask and its spectra was determined using partial least square regression analysis and simple linear regression analysis. The best fit obtained for calibration correlation analysis (R2 = 0.944, RSE: 1.24%), together with the good extractable PHA predictions (RSE = 0.51%) demonstrate that the proposed methodology constitutes a fast way with high potential for the determination of extractable PHA. Based on its simplicity and flexibility, its application would be suitable in routine monitoring and rapid quantification in large-scale processes involving PHA metabolism.

Chromatography is an important biophysical technique that enables the separation, identification, and purification of the components of a mixture for qualitative and quantitative analysis. Proteins can be purified based on characteristics such as size and shape, total charge, hydrophobic groups present on the surface, and binding capacity with the stationary phase. Four separation techniques based on molecular characteristics and interaction type use mechanisms of ion exchange, surface adsorption, partition, and size exclusion. Other chromatography techniques are based on the stationary bed, including column, thin layer, and paper chromatography. Column chromatography is one of the most common methods of protein purification.

Chromatography is an important biophysical technique that enables the separation, identification, and purification of the components of a mixture for qualitative and quantitative analysis. Proteins can be purified based on characteristics such as size and shape, total charge, hydrophobic groups present on the surface, and binding capacity with the stationary phase. Four separation techniques based on molecular characteristics and interaction type use mechanisms of ion exchange, surface adsorption, partition, and size exclusion. Other chromatography techniques are based on the stationary bed, including column, thin layer, and paper chromatography. Column chromatography is one of the most common methods of protein purification.

Engineering cofactor specificity of enzymes is a promising approach that can expand the application of enzymes for biocatalytic production of industrially relevant chemicals. Until now, only NADPH-dependent imine reductases (IREDs) are known. This limits their applications to reactions employing whole cells as a cost-efficient cofactor regeneration system. For applications of IREDs as cell-free catalysts, (i) we created an IRED variant showing an improved activity for NADH. With rational design we were able to identify four residues in the (R)-selective IRED from Streptomyces GF3587 (IR-Sgf3587), which coordinate the 2′-phosphate moiety of the NADPH cofactor. From a set of 15 variants, the highest NADH activity was caused by the single amino acid exchange K40A resulting in a 3-fold increased acceptance of NADH. (ii) We showed its applicability using an immobilisate obtained either from purified enzyme or from lysate using the EziG™ carriers. Applying the variant and NADH, we reached 88% conversion in a preparative scale biotransformation when employing 4% (w/v) 2-methylpyrroline. (iii) We demonstrated a one-enzyme cofactor regeneration approach using the achiral amine N-methyl-3-aminopentanone as a hydrogen donor co-substrate.

The objective of this study was to evaluate the clinical significance of serum ADP-ribosylation and NAD glycohydrolase activity in patients with colorectal cancer (CRC). A total of 108 patients with CRC who underwent curative surgery and 20 healthy volunteers were enrolled in this study. ADP-ribosylation and NAD glycohydrolase activity levels were determined. The association of ADP-ribosylation and NAD glycohydrolase with clinical and laboratory factors and their impact on overall survival (OS) and disease free survival (DFS) were shown. The preoperative ADP-ribosylation and NAD glycohydrolase activity levels were significantly higher in patients with CRC than in the control group (p < 0.001). ADP-ribosylation and NAD glycohydrolase activity levels were correlated with tumor stage (p = 0.05, p = 0.001), stage of disease (p < 0.001, p < 0.001), serum CEA level (p < 0.001, p < 0.001), and site of lesion (p < 0.001, p < 0.001), respectively. Patients with high ADP-ribosylation had significantly unfavorable OS and DFS compared with those with lower levels (p < 0.001, p < 0.001), respectively. Moreover, the patients with high NAD glycohydrolase activity showed significantly worse OS and DFS rates, similar to ADP-ribosylation. Serum levels of ADP-ribosylation and NAD glycohydrolase activity correlate well with tumor stage, stage of disease, serum CEA level, and site of lesion. In conclusion, elevated levels of preoperative ADP-ribosylation and NAD glycohydrolase levels in serum are associated with poor prognosis in patients with CRC.