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    4-phenyl butyric acid improves hepatic ischemia/reperfusion and affects gene expression of ABC transporter Abcc5 in rats
    (Medicinska Naklada, 2023) Guven, Bulent Baris; Tanoglu, Alpaslan; Ozcelik, Fatih; Tanoglu, Esra Guzel; Terzi, Neslihan Kaya
    Aim To assess the effects of 4-phenyl butyric acid (PBA) on oxidative stress, inflammation, liver histology, endoplasmic (ER) reticulum stress, and the expression levels of ATP -binding cassette transporter family members in a hepatic ischemia-reper fusion (IR) model.Methods Thirty-five rats were randomly divided into five groups: sham, IR, IR + 100 mg kg-1 PBA, IR + 200 mg kg-1 PBA, and IR + placebo. After sacrifice, we assessed serum biochemical variables, myeloperoxidase (MPO), malondialdehyde (MDA), total antioxidant status (TAS), and total oxidant status (TOS). The expression levels of Abcc (2 and 5), Abcg2, Abcf2, Ire1-alpha, and Perk genes were measured with a quantitative real-time polymerase chain reaction.Results Serum biochemical variables, MPO, MDA, TAS, and TOS levels of the PBA groups (especially in the low dose group) were lower than in the IR and placebo group (P < 0.05). Histological tissue damage in the IR group was more severe than in the PBA groups. Ire1-alpha and Perk expression levels were significantly lower in the PBA groups than the IR group (P < 0.001). Abcc (2 and 5) and Abcg2 expression levels were significantly lower in the IR group than in the sham and PBA groups (P < 0.001, P < 0.035, and P < 0.009, respectively).Conclusions The use of PBA significantly positively affected IR injury, which makes PBA a candidate treatment to reduce liver IR.
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    Ankaferd hemostat (ABS) as a potential mucosal topical agent for the management of COVID-19 syndrome based on its PAR-1 inhibitory effect and oestrogen content
    (Churchill Livingstone, 2020) Beyazit, Fatma; Beyazit, Yavuz; Tanoglu, Alpaslan; Haznedaroglu, Ibrahim C.
    COVID-19 due to the SARS-CoV-2 infection is a multi-systemic immune syndrome affecting mainly the lungs, oropharyngeal region, and other vascular endothelial beds. There are tremendous ongoing efforts for the aim of developing drugs against the COVID-19 syndrome-associated inflammation. However, currently no specific medicine is present for the absolute pharmacological cure of COVID-19 mucositis. The re-purposing/re-positioning of already existing drugs is a very important strategy for the management of ongoing pandemy since the development of a new drug needs decades. Apart from altering angiotensin signaling pathways, novel drug candidates for re-purposing comprise medications shall target COVID-19 pathobiology, including pharmaceutical formulations that antagonize proteinase-activated receptors (PARs), mainly PAR-1. Activation of the PAR-1, mediators and hormones impact on the hemostasis, endothelial activation, alveolar epithelial cells and mucosal inflammatory responses which are the essentials of the COVID-19 pathophysiology. In this context, Ankaferd hemostat (Ankaferd Blood Stopper, ABS) which is an already approved hemostatic agent affecting via vital erythroid aggregation and fibrinogen gamma could be a potential topical remedy for the mucosal management of COVID-19. ABS is a clinically safe and effective topical hemostatic agent of plant origin capable of exerting pleiotropic effects on the endothelial cells, angiogenesis, cell proliferation and vascular dynamics. ABS had been approved as a topically applied hemostatic agent for the management of post-surgical/dental bleedings and healing of infected inflammatory mucosal wounds. The anti-inflammatory and proteinase-activated receptor axis properties of ABS with a considerable amount of oestrogenic hormone presence highlight this unique topical hemostatic drug regarding the clinical re-positioning for COVID-19-associated mucositis. Topical ABS as a biological response modifier may lessen SARS-CoV-2 associated microthrombosis, endothelial dysfunction, oropharyngeal inflammation and mucosal lung damage. Moreover, PAR-1 inhibition ability of ABS might be helpful for reducing the initial virus propagation and mocasal spread of COVID-19.
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    Evaluation of endothelial dysfunction in patients with familial Mediterranean fever: the relationship between the levels of asymmetric dimethylarginine and endocan with carotid intima-media thickness and endothelium-dependent vasodilation
    (Springer London Ltd, 2017) Ozalper, Veysel; Kara, Muammer; Tanoglu, Alpaslan; Cetindagli, Ibrahim; Ozturker, Coskun; Hancerli, Yusuf; Hira, Serdar
    It has been suggested that there is an ongoing subclinical inflammation in familial Mediterranean fever (FMF) patients also in attack-free periods as well. Due to this ongoing inflammation, endothelial dysfunction (ED) may develop. Previously, ED has been suggested to increase the risk of the atherosclerosis and cardiovascular disease (CVD). Endocan is recognized as a specific molecule of the endothelium and has been shown to increase in some cases associated with inflammation. However, there is not sufficient data whether those with FMF could develop ED in the early period of life. In this study, we aimed to investigate ED and its relation with endocan in young FMF patients. A total of 57 male patients diagnosed with FMF according to the Tel Hashomer criteria and a total of 33 healthy males with similar characteristics to the patient group were included in this research. Complete blood count, erythrocyte sedimentation rate (ESR), fibrinogen, serum glucose, serum LDL cholesterol (LDL-C) and triglyceride (TG), asymmetric dimethylarginine (ADMA), and endocan levels were tested from fasting blood samples. Moreover, carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD) were measured. The endocan levels of the FMF patients during an attack-free period were significantly higher than those of the control group (p < 0.001). On the other hand, FMD measurements were significantly lower among FMF patients (p < 0.001). ADMA levels were higher in the patient group; however, this difference was similar (p > 0.05). CIMT values were similar among FMF patients and healthy controls (p > 0.05). These results have suggested that ED may develop in the patients with FMF who have no additional CVD risk, even during young adulthood, and endocan may be a favorable biomarker at demonstration of ED than ADMA among FMF patients.
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    Midkine level may be used as a noninvasive biomarker in Crohn's disease
    (Tubitak Scientific & Technological Research Council Turkey, 2020) Kekilli, Murat; Tanoglu, Alpaslan; Karaahmet, Fatih; Dogan, Zeynal; Can, Murat; Sayilir, Abdurrahim; Cakal, Basak
    Background/aim: Crohn's disease (CD) is a kind of inflammatory bowel disease. Midkine (MDK) is an endogenous inflammatory marker. We aimed to investigate the relationship between MDK levels and inflammation and hence determine whether MDK can be used as a noninvasive biomarker in active CD. Materials and methods: Sixty-five consecutive patients over the age of 18 with CD and 36 healthy controls were included in this study. CD patients' venous blood samples were taken before treatment. Serum MDK levels were determined in human plasma samples by enzyme-linked immunosorbent assay (ELISA) method. Results: The mean age of the study patients was 44.8 +/- 12.5 years, 35 patients were female, and 30 were male. Of these 65 patients, 37 had active CD and 28 were in the remission phase. MDK levels were significantly higher in active and remission CD than in healthy controls (P = 0.01, P = 0.038, respectively). Conclusion: We report that there is an association between MDK levels and CD activation, and therefore with enhanced inflammation. MDK levels were significantly correlated with inflammatory indices. In line with our findings, we suggest the theory that MDK inhibitors may be useful in treating Crohn's disease.