Browsing by Author "Cansev, Mehmet"
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Publication Anti-apoptotic and anti-oxidant effects of systemic uridine treatment in an experimental model of sciatic nerve injury(Türk Nöroloji Derneği, 2021-01-01) Khezri, Marzieh Karimi; Turkkan, Alper; Khezri, Marzieh Karimi; Koç, Cansu; KOÇ, CANSU; Salman, Berna; SALMAN, BERNA; Levent, Pinar; Cakir, Aysen; Kafa, Ilker Mustafa; Cansev, Mehmet; Bekar, Ahmet; ÇAKIR, AYŞEN; KAFA, İLKER MUSTAFA; CANSEV, MEHMET; BEKAR, AHMET; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Anatomi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0002-6097-5585; 0000-0001-8309-0934; 0000-0003-2918-5064; AAA-4754-2022; ABX-9081-2022; A-6819-2018AIM: To investigate the anti-apoptotic and anti-oxidant effects of systemic uridine treatment in a rat model of sciatic nerve injury.MATERIAL and METHODS: Thirty-two adult male rats were equally randomized to Sham, Control, U100, and U500 groups. Sham rats received a sham operation by exposing the right sciatic nerve without transection, while those in the Control, U100, and U500 groups underwent right sciatic nerve transection followed by immediate primary anostomosis. Sham and Control groups received saline (0.9% NaCl) injections intraperitoneally (i.p.), while U100 and U500 groups received 100 mg/kg and 500 mg/kg uridine injections (i.p.), respectively, once a day for 7 days after the surgery. Rats in all the groups were sacrificed on the eighth day; sciatic nerve samples were analyzed for apoptosis by Western Blotting and for oxidation parameters including myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) by Enzyme-Linked Immunosorbent Assay (ELISA).RESULTS: Uridine treatment at the dose of 500 mg/kg significantly decreased as apoptosis determined by Caspase-3/Actin ratio and exhibited significant anti-oxidant effects as determined by decreased levels of MPO and MDA as well as increased levels of SOD, GPx, and CAT compared to controls. Uridine at 100 mg/kg was only found to decrease the Caspase-3/Actin ratio, although it significantly decreased MDA and increased CAT levels compared to controls.CONCLUSION: Treatment with uridine reduces apoptosis and oxidation in a rat model of sciatic nerve injury dose-dependently. Thus, uridine may be beneficial in peripheral nerve regeneration by exhibiting anti-apoptotic and anti-oxidant effects.Publication Antioxidative effects of uridine in a neonatal rat model of hyperoxic brain injury(TÜBİTAK, 2020-05-31) Al, Nevin; Çakir, Aysen; Koç, Cansu; Cansev, Mehmet; Alkan, Tülin; ÇAKIR, AYŞEN; KOÇ, CANSU; CANSEV, MEHMET; ALKAN, TÜLİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; 0000-0002-6097-5585; 0000-0003-2918-5064; 0000-0001-6466-5042; AAA-4754-2022; A-6819-2018; M-9071-2019; AAH-1792-2021Background/aim: Premature birth is a major problem that results in an increased risk of mortality and morbidity. The management of such infants consists of supraphysiological oxygen therapy, which affects brain development due, in part, to the deterioration caused by reactive oxygen species (ROS). We showed previously that exogenously administered uridine provides neuroprotection in a neonatal rat model of hyperoxic brain injury. Hence, the aim of the present study was to investigate the effects of uridine on ROS in the same setting.Materials and methods: Hyperoxic brain injury was induced by subjecting a total of 53 six-day-old rat pups to 80% oxygen (the hyperoxia group) for a period of 48 h. The pups in the normoxia group continued breathing room air (21% oxygen). Normoxia + saline or hyperoxia + saline or hyperoxia + uridine 100 mg/kg or hyperoxia + uridine 300 mg/kg or hyperoxia + uridine 500 mg/kg was injected intraperitoneally (i. p.) 15 min prior to the hyperoxia procedure. The pups were decapitated and the brains were homogenized to analyze superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), and malondialdehyde (MDA) enzymes as well as DJ-1 (protein deglycase DJ-1) - an oxidative stress-sensitive protein.Results: Hyperoxia-induced may cause overproduction of oxygen radicals and the oxidant/antioxidant balance may be disturbed in the brain. Brain MPO and MDA levels were significantly increased in saline-receiving pups exposed to hyperoxia. Brain SOD and GSH-Px levels were significantly decreased in saline-receiving pups exposed to hyperoxia. Our results showed that uridine administration prevented the hyperoxia-induced decrease in SOD and GSH-Px while counteracting the hyperoxia-induced increase in MPO and MDA in a dose-dependent manner. Uridine also increased the DJ-1 levels in brains of rat pups subjected to hyperoxia.Conclusion: These data suggest that uridine exhibits antioxidative properties which may mediate the protective effects of uridine in a neonatal rat model of hyperoxic brain injury.Item Breast milk choline contents are associated with inflammatory status of breastfeeding women(Sage Publications, 2014-05) Ulus, İsmail Hakkı; Özarda İlçol, Yeşim; Cansev, Mehmet; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Eczacılık Anabilim Dalı.; AAL-8873-2021; M-9071-2019; 35741320500; 8872816100Background: Choline is an important component of human breast milk and its content varies considerably among breastfeeding women and lactation periods. Objective: The aim of this study was to assess the relationship between breast milk choline contents and inflammatory status in breastfeeding women. Methods: Breast milk choline compounds and serum C-reactive protein (CRP) concentrations were determined in breastfeeding women at 1 to 3 (n = 53) or 22 to 180 (n = 54) days postpartum, expressing colostrum or mature milk, respectively. Results: Median concentrations of free choline, phosphocholine, glycerophosphocholine, phospholipid-bound choline, and total choline were 71, 38, 96, 194, and 407 mol/L or 93, 351, 958, 186, and 1532 mol/L in colostrum or mature milk, respectively. Median serum CRP concentrations were 4.13 mg/L and 0.33 mg/L at 1 to 3 days and 22 to 180 days postpartum, respectively. At 1 to 3 days postpartum, milk free choline, phosphocholine, glycerophosphocholine, and total choline as well as serum CRP concentrations were significantly higher in breastfeeding women who delivered by cesarean section than those who delivered via the vaginal route. Serum CRP concentration was positively correlated with colostrum free choline (r=0.703; P<.001), phosphocholine (r=0.759; P<.001), glycerophosphocholine (r=0.706; P<.001), and total choline (r=0.693; P<.001), whereas it was negatively correlated (r=-0.442; P<.001) with colostrum phospholipid-bound choline. Serum CRP was also negatively correlated with mature milk free choline (r=-0.278; P<.05), but no correlation was found between serum CRP and other choline compounds in mature milk. Conclusion: These data show that the concentrations of milk choline compounds are associated with inflammatory status of breastfeeding women, particularly during the first few days after delivery.Item Cardiovascular effects of CDP-choline and its metabolites: Involvement of peripheral autonomic nervous system(Elsevier Science, 2007-12-22) Cansev, Mehmet; Yılmaz, Mustafa Serdar; İlçöl, Yeşim Özarda; Hamurtekin, Emre; Ulus, İsmil Hakkı; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; 0000-0003-2918-5064; 0000-0001-9496-1475; AAH-1571-2021; D-5340-2015; M-9071-2019; AAL-8873-2021; 8872816100; 8895544100; 35741320500; 8717648500; 7004271086Intraperitoneal administration of CDP-choline (200-900 mu mol/kg) increased blood pressure and decreased heart rate of rats in a dose- and time-dependent manner. These responses were accompanied by elevated serum concentrations of CDP-choline and its metabolites phosphocholine, choline, cytidine monophosphate and cytidine. Blood pressure increased by intraperitoneal phosphocholine (200-900 mu mol/ kg), while it decreased by choline (200-600 mu mol/kg) administration; phosphocholine or choline administration (up to 600 mu mol/kg) decreased heart rate. Intraperitoneal cytidine monophosphate (200-600 mu mol/kg) or cytidine (200-600 mu mol/kg) increased blood pressure without affecting heart rate. Pressor responses to CDP-choline, phosphocholine, cytidine monophosphate or cytidine were not altered by pretreatment with atropine methyl nitrate or hexamethonium while hypotensive effect of choline was reversed to pressor effect by these pretreatments. Pretreatment with atropine plus hexamethonium attenuated or blocked pressor response to CDP-choline or phosphocholine, respectively. Heart rate responses to CDP-choline, phospbocholine and choline were blocked by atropine and reversed by hexamethonium. Cardiovascular responses to CDP-choline, phosphocholine and choline, but not cytidine monophosphate or cytidine, were associated with elevated plasma catecholamines concentrations. Blockade of alpha-adrenoceptors by prazosin or yohimbine attenuated pressor response to CDP-choline while these antagonists blocked pressor responses to phosphocholine or choline. Neither bilateral adrenalectomy nor chemical sympathectomy altered cardiovascular responses to CDPcholine, choline, cytidine monophosphate or cytidine. Sympathectomy attenuated pressor response to phosphocholine. Results show that intraperitoneal administration of CDP-choline and its metabolites alter cardiovascular parameters and suggest that peripheral cholinergic and adrenergic receptors are involved in these responses.Item CDP-choline modulates matrix metalloproteinases in rat sciatic injury(Elsevier, 2015-10-01) Gündoğdu, Elif Başaran; Bekar, Ahmet; Türkyılmaz, Mesut; Gümüş, Abdullah; Kafa, İlker Mustafa; Cansev, Mehmet; Uludağ Üniversitesi/Tıp Fakültesi/Nöroşirürji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Eczacılık Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Anatomi Anabilim Dalı.; 0000-0002-9140-4195; 0000-0001-8309-0934; 0000-0003-2918-5064; AAG-7125-2021; M-9071-2019; 57016583400; 6603677218; 56320252500; 56473463900; 8450193200; 8872816100Background: CDP-choline (cytidine-5'-diphosphocholine) improves functional recovery, promotes nerve regeneration, and decreases perineural scarring in rat peripheral nerve injury. The aim of the present study was to investigate the mechanism of action of CDPcholine with regard to matrix metalloproteinase (MMP) activity in the rat-transected sciatic nerve injury model. Materials and methods: Male Wistar rats were randomized into Sham, Saline, and CDPcholine groups. Rats in Sham group received Sham surgery, whereas rats in Saline and CDP-choline groups underwent right sciatic nerve transection followed by immediate primary saturation and injected intraperitoneally with 0.9% NaCl (1 mL/kg) and CDP-choline (600 mg/kg), respectively. Sciatic nerve samples were obtained 1, 3, and 7 d after the surgery and analyzed for levels and activities of MMP-2 and MMP-9, levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-3, and axonal regeneration. Results: CDP-choline treatment decreased the levels and activities of MMP-2 and MMP-9, whereas increasing levels of TIMP-1 and TIMP-3 significantly on the third and seventh day after injury compared to Saline group. In addition, CDP-choline administration resulted in new axon formation and formation and advancement of myelination on newly formed islets (compartments) of axonal regrowth. Conclusions: Our data show, for the first time, that CDP-choline modulates MMP activity and promotes the expression of TIMPs to stimulate axonal regeneration. These data help to explain one mechanism by which CDP-choline provides neuroprotection in peripheral nerve injury.Item CDP-choline reduces severity of intestinal injury in a neonatal rat model of necrotizing enterocolitis(Academic Press Inc Elsevier Science, 2013-07) Çetinkaya, Merih; Çekmez, Ferhat; Canpolat, Fuat Emre; Uysal, Sema; Tunç, Turan; Sarıcı, Serdar Ümit; Cansev, Mehmet; Tayman, Cüneyt; Kafa, İlker Mustafa; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Anatomi Anabilim Dalı.; M-9071-2019; AAG-7125-2021; 8872816100; 12243787300; 8450193200Background: Cytidine 5'-diphosphocholine (CDP-choline) is an endogenous intermediate in the biosynthesis of phosphatidylcholine, a contributor to the mucosal defense of the intestine. The aim of this study was to evaluate the possible cytoprotective effect of CDP-choline treatment on intestinal cell damage, membrane phospholipid content, inflammation, and apoptosis in a neonatal rat model of necrotizing enterocolitis (NEC). Methods: We divided a total of 30 newborn pups into three groups: control, NEC, and NEC + CDP-choline. We induced NEC by enteral formula feeding, exposure to hypoxia-hyperoxia, and cold stress. We administered CDP-choline intraperitoneally at 300 mg/kg/d for 3 d starting from the first day of life. We evaluated apoptosis macroscopically and histopathologically in combination with proinflammatory cytokines in the gut samples. Moreover, we determined membrane phospholipid levels as well as activities of xanthine oxidase, superoxide dismutase, glutathione peroxidase, and myeloperoxidase enzymes and the malondialdehyde content of intestinal tissue. Results: Mean clinical sickness score, macroscopic gut assessment score, and intestinal injury score were significantly improved, whereas mean apoptosis score and caspase-3 levels were significantly reduced in pups in the NEC + CDP-choline group compared with the NEC group. Tissue proinflammatory cytokine (interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha) levels as well as tissue malondialdehyde content and myeloperoxidase activities were reduced, whereas glutathione peroxidase and superoxide dismutase activities were preserved in the NEC + CDP-choline group. In addition, NEC damage reduced intestinal tissue membrane phospholipids, whereas CDP-choline significantly enhanced total phospholipid and phosphatidylcholine levels. Long-term follow-up in additional experiments revealed increased body weight, decreased clinical sickness scores, and enhanced survival in CDP-cholineereceiving versus saline-receiving pups with NEC lesions. Conclusions: Our study reports, for the first time, beneficial effects of CDP-choline treatment on intestinal injury in a neonatal rat model of NEC. Our data suggest that CDP-choline may be used as an effective therapeutic agent to prevent NEC.Item CDP-KOLİN'in kardiyovasküler, metabolik ve nöroendokrin etkileri(Uludağ Üniversitesi, 2003) Cansev, Mehmet; Ulus, İsmail Hakkı; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı.Bu çalışmada sıçanlara periton içi (i.p.) yolla verilen CDP-kolin'in kardiyovasküler, metabolik ve nöroendokrin etkileri incelendi. İ.p. yolla zerk edilen CDP-kolin (105, 210, 315 ve 473 mg/kg) kan basıncını doza ve zamana bağlı olarak 17-35 mm Hg kadar artırırken kalp hızını doza ve zamana bağlı olarak 32-53 atım/dakika kadar azalttı. CDP-kolin'in kan basıncını yükseltici etkisi atropin metil nitrat veya hekzametonyum gibi kolinerjik reseptör antagonistleri ve prazosin, yohimbin veya propranolol gibi adrenerjik reseptör antagonistleri ile ön tedaviyi takiben ya da bilateral adrenalektomi sonrası değişmedi. CDP-kolin'in bradikardik etkisi ise, atropin metil nitrat veya prazosin ön tedavisi sonrası bloke oldu, hekzametonyum ön tedavisini takiben tersine döndü. Bradikardik etki yohimbin ön tedavisinden ve bilateral adrenalektomiden etkilenmedi. Propranolol ön tedavisi sonrası kalp atım hızında düşüş gözlendi ve CDP-kolin verilmesinden sonra da bu düşme değişmedi. CDP-kolin (105, 210 ve 315 mg/kg; i.p.) serum glukoz düzeylerini zamana bağlı olarak 16-29 mg/dl kadar artırdı. Hekzametonyum ön tedavisi bu hiperglisemik etkiyi bloke ederken atropin metil nitrat değiştirmedi. CDP-kolin'in hiperglisemik etkisi yohimbin ön tedavisi veya bilateral adrenalektomi ile bloke olurken, propranolol ön tedavisi hiperglisemik etkiyi değiştirmedi. CDP-kolin (210 ve 315 mg/kg; i.p.) zerkini takiben 10. dakikada plazma adrenalin düzeyleri anlamlı olarak arttı. 315 mg/kg CDP-kolin sonrasında 5, 10, ve 20. dakikalarda plazma noradrenalin düzeyleri anlamlı olarak arttı. 315 ve 473 mg/kg dozlarında serum insülin düzeyleri ve tüm dozlarda (105, 210, 315 ve 473 mg/kg) plazma glukagon düzeyleri zerki takiben 10. dakikada anlamlı şekilde arttı. Sonuç olarak; CDP-kolin çeşitli kardiyovasküler, metabolik ve nöroendokrin etkilere sahiptir. CDP-kolin'in tüm bu etkilerinde açığa çıkan kolin'in yol açtığı kolinerjik aktivasyonun aracılığı rol oynayabilir.Item Central choline suppresses plasma renin response to graded haemorrhage in rats(Wiley, 2008-10) Işbil Büyükcoşkun, Naciye; İlçöl, Yeşim Özarda; Cansev, Mehmet; Hamurtekin, Emre; Özlük, Kasım; Ulus, Ismail Hakki; Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Klinik Farmakoloji Anabilim Dalı.; 0000-0003-2918-5064; AAL-8873-2021; M-9071-2019; D-5340-2015; AAH-1692-2021; 55665951400; 35741320500; 8872816100; 8717648500; 6602676331; 70042710861. Central administration of choline increases blood pressure in normotensive and hypotensive states by increasing plasma concentrations of vasopressin and catecholamines. We hypothesized that choline could also modulate the renin-angiotensin pathway, the third main pressor system in the body. 2. Plasma renin activity (PRA), which serves as an index of the function of the peripheral renin-angiotensin system, was determined in rats subjected to graded haemorrhage following central choline administration. 3. Intracerebroventricular (i.c.v.) injection of choline (12.5-150 mu g), a precursor of the neurotransmitter acetylcholine (ACh), inhibited the increase in PRA in rats subjected to graded haemorrhage by sequential removal of 0.55 mL blood/100 g bodyweight. Choline, in the range 50-150 mu g, increased blood pressure. 4. Intraperitoneal (i.p.) administration of 150 mu g choline failed to alter blood pressure and plasma renin responses to graded haemorrhage. Administration of a higher dose (90 mg/kg, i.p.) of choline decreased blood pressure and enhanced PRA in the first two blood samples obtained during the graded haemorrhage. Physostigmine (10 mu g, i.c.v.), ACh (10 mu g, i.c.v.), carbamylcholine (10 mu g, i.c.v.) and cytidine 5'-diphosphocholine (CDP-choline; 250 mu g, i.c.v.) increased blood pressure and attenuated plasma renin responses to graded haemorrhage. 5. Inhibition of PRA by i.c.v. choline was abolished by i.c.v. pretreatment with mecamylamine (50 mu g), but not atropine (10 mu g). Blood pressure responses to choline (150 mu g) were attenuated by pretreatment with both mecamylamine and atropine. 6. Inhibition of PRA in response to central choline administration was associated with enhanced plasma vasopressin and catecholamine responses to graded haemorrhage. Pretreatment of rats with a vasopressin antagonist reversed central choline-induced inhibition of plasma renin responses to graded haemorrhage without altering the blood pressure response. 7. In conclusion, central administration of choline inhibits the plasma renin response to graded haemorrhage. Nicotinic receptor activation and an increase in plasma vasopressin appear to be involved in this effect.Publication Changes in choline and cholinesterase in saliva of dogs with parvovirus infection(Elsevier, 2021-01-01) Kocatürk, Meriç; Tecles, Fernando; Yalçın, Ebru; Cihan, Hüseyin; Tural, Merve; Levent, Pınar; Cansev, Mehmet; Ceron, Jose J.; Yılmaz, Zeki; KOCATÜRK, MERİÇ; YALÇIN, EBRU; CİHAN, HÜSEYİN; Tural, Merve; Levent, Pınar; CANSEV, MEHMET; YILMAZ, ZEKİ; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/İç Hastalıkları Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; 0000-0002-2849-1222; 0000-0001-6703-4908; 0000-0003-2918-5064; 0000-0001-9836-0749; M-9071-2019; GDR-9018-2022 ; V-5578-2017; ACP-9956-2022; A-9637-2008; ABH-3742-2020; DDR-1481-2022This study investigated the changes in choline (Ch) and butyrylcholinesterase (BChE) in saliva in canine parvovirosis (CP) as a model of sepsis, and their correlations with these analytes in serum and with other markers of inflammation such as white blood cell count (WBC) and serum C-reactive protein (CRP). A total of 30 dogs with CP were sampled for saliva and serum at presentation, and 10 healthy puppies were also sampled as controls. Salivary Ch was higher in dogs with CP (P < 0.001) showing a positive correlation with CRP, whereas no differences were observed in salivary BChE. This is the first report in which Ch is measured in saliva of dogs and based in the results of this study, salivary Ch could be potentially used as biomarker of the severity of CP.Item Changes in serum proteins after endotoxin administration in healthy and choline-treated calves(BMC, 2016-09-10) İnan, Oya Eralp; Baykal, Ahmet T.; Hacariz, O.; Hatipoğlu, I.; Tvarijonaviciute, Asta; Ceron, Jose; Ulus, İsmail Hakkı; Yılmaz, Zeki; Cansev, Mehmet; Kocatürk, Meriç; Uludağ Üniversitesi/Veteriner Fakültesi/Dahiliye Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Eczacılık Anabilim Dalı.; 0000-0001-9836-0749; 0000-0003-2918-5064; M-9071-2019; V-5578-2017; 35944810500; 36437200800; 8872816100Background: This study aimed to investigate the possible serum protein changes after endotoxin administration in healthy and choline-treated calves using proteomics. These results are expected to contribute to the understanding of the pathophysiological mechanisms of endotoxemia and the beneficial effect of choline administration in this clinical situation. Methods: Healthy-calves (n = 20) were divided into 4 groups: Control, Choline treated (C), Lipopolysaccharide administered (LPS), and LPS + C. Control calves received 0.9 % NaCl injection. Calves in C and LPS + C groups received choline chloride (1 mg/kg/iv). Endotoxin (LPS) was injected (2 mu g/kg/iv) to the calves in LPS and LPS + C groups. Serum samples were collected before and after the treatments. Differentially expressed proteins (> 1.5 fold-change relative to controls) were identified by LC-MS/MS. Results: After LPS administration, 14 proteins increased, and 13 proteins decreased within 48 h as compared to controls. In the LPS group, there were significant increases in serum levels of ragulator complex protein (189-fold) and galectin-3-binding protein (10-fold), but transcription factor MafF and corticosteroid binding globulin were down regulated (>= 5 fold). As compared with the LPS group, in LPS + C group, fibrinogen gamma-B-chain and antithrombin were up-regulated, while hemopexin and histone H4 were down-regulated. Choline treatment attenuated actin alpha cardiac muscle-1 overexpression after LPS. Conclusions: LPS administration produces changes in serum proteins associated with lipid metabolism, immune and inflammatory response, protein binding/transport, cell adhesion, venous thrombosis, cardiac contractility and blood coagulation. The administration of choline is associated with changes in proteins which can be related with its beneficial effect in this clinical situation.Item Choline or CDP-choline alters serum lipid responses to endotoxin in dogs and rats: Involvement of the peripheral nicotinic acetylcholine receptors(Lippincott Williams & Wilkins, 2009-09) İlçöl, Yeşim Özarda; Yılmaz, Zeki; Cansev, Mehmet; Ulus, İsmail Hakkı; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Veterinerlik Fakültesi/İç Hastalıkları Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı.; 0000-0003-2918-5064; 0000-0001-9836-0749; D-5340-2015; M-9071-2019; AAL-8873-2021; 35741320500; 35944810500; 8872816100; 7004271086We showed previously that choline administration protects dogs from endotoxin-induced multiple organ injury and platelet dysfunctions. Because sepsis/endotoxemia is associated with alterations in lipid metabolism, we have investigated whether choline or cytidine-5'-diphosphate choline, a choline donor, alters serum lipid responses to endotoxin in dogs and rats. In response to endotoxin, serum concentrations of triglycerides, choline-containing phospholipids, total cholesterol, and high-density lipoprotein cholesterol increased in a dose- and time-related manner. Administration of choline (20 mg/kg i.v. in dogs or 90 mg/kg i.p. in rats) or cytidine-5'-diphosphate choline (70 mg/kg i.v. in dogs) 5 min before and 4 and 8 h after endotoxin blocked or attenuated the increases in serum triglycerides, total cholesterol, and nonesterified fatty acids. Endotoxin-induced elevations in serum phospholipid levels did not change in rats and were enhanced in dogs by choline. In rats, serum lipid response to endotoxin was accompanied by severalfold elevations in serum levels of hepatorenal injury markers; their elevations were also blocked by choline. Pretreatment with hexamethonium blocked choline's effects on serum lipids and hepatorenal injury markers. Pretreatment with atropine blocked endotoxin-induced elevations in serum lipid and hepatorenal injury markers, but failed to alter choline's actions on these parameters. Choline treatment improved survival rate of rats in lethal endotoxin shock. In conclusion, these data show that choline treatment alters serum lipid responses to endotoxin and prevents hepatorenal injury during endotoxemia through a nicotinic acetylcholine receptor-mediated mechanism. Hence, choline and choline-containing compounds may have a therapeutic potential in the treatment of endotoxemia/sepsis.Item Choline or CDP-choline attenuates coagulation abnormalities and prevents the development of acute disseminated intravascular coagulation in dogs during endotoxemia(Lippincott Williams & Wilkins, 2010-06) Ulus, İsmail Hakkı; Yılmaz, Zeki; İlçöl, Yeşim Özarda; Cansev, Mehmet; Eralp, Oya; Kocatürk, Meriç; Uludağ Üniversitesi/Veterinerlik Fakültesi/Klinik Bilimler Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; 0000-0002-4242-8609; 0000-0001-9836-0749; 0000-0003-2918-5064; M-9071-2019; AAG-2943-2020; AAL-8873-2021; 35944810500; 35741320500; 8872816100; 24472964600; 36437200800Sepsis/endotoxemia causes platelet dysfunctions, abnormalities in coagulation and hemostatic mechanisms leading to organ dysfunctions and mortality. Choline prevents organ injury and improves survival during endotoxemia. The main objective of the present study was to determine the effects of choline or cytidine-5'-diphosphocholine (CDP-choline) on endotoxin-induced activation of coagulation and development of disseminated intravascular coagulation (DIC). Dogs were treated intravenously (i.v.) with saline, choline (20 mg/kg), or CDP-choline (70 mg/kg) three times with 4-h intervals starting 5 min before i.v. injection of endotoxin (1 mg/kg). Platelet counts and functions, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, coagulation factors, D-dimer and antithrombin (AT) were measured before and at 0.5-96 h after endotoxin. Circulating platelet, fibrinogen, coagulation factors and AT were decreased, whereas PT and aPTT were prolonged and serum D-dimer levels were elevated after endotoxin. Endotoxin-induced reductions in platelet counts and functions, fibrinogen, coagulation factors and AT were attenuated or blocked by choline or CDP-choline. Choline or CDP-choline blocked endotoxin-induced prolongation in PT and aPTT and enhancement in D-dimer. Elevated DIC scores were attenuated by choline and blocked by CDP-choline. Choline administration increased serum choline concentrations and caused bradycardia. Choline also increased choline and acetylcholine contents of circulating mononuclear cells and inhibited radioligand binding to their cholinergic receptors. These data show that choline administration, as choline chloride or CDP-choline, restores the abnormalities in the primary, secondary, and tertiary hemostasis and prevents the development of DIC during experimental endotoxemia in dogs probably by increasing both neuronal and nonneuronal cholinergic activity. Blood Coagul Fibrinolysis 21:339-348Publication Choline or cdp-choline restores hypotension and improves myocardial and respiratory functions in dogs with experimentally-induced endotoxic shock(Elsevier, 2021-10-27) Ozarda, Yesim; Ceron, Jose Joaquin; Buturak, Ali; Ulus, Ismail H.; Kocaturk, Meric; KOCATÜRK, MERİÇ; Yilmaz, Zeki; YILMAZ, ZEKİ; Cansev, Mehmet; CANSEV, MEHMET; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Veteriner Fakültesi.; 0000-0002-2849-1222; 0000-0001-9836-0749; 0000-0003-2918-5064; 0000-0002-8654-1793; H-9043-2015; D-5340-2015; V-5578-2017; A-9637-2008Endotoxin shock is associated with severe impairments in cardiovascular and respiratory functions. We showed previously that choline or cytidine-5 '-diphosphocholine (CDP-choline) provides beneficial effects in experimental endotoxin shock in dogs. The objective of the present study was to determine the effects of choline or CDPcholine on endotoxin-induced cardiovascular and respiratory dysfunctions. Dogs were treated intravenously (i.v.) with saline or endotoxin (LPS, 0.1 mg/kg) 5 min before i.v. infusion of saline, choline (20 mg/kg) or CDP-choline (70 mg/kg). Blood pressure, cardiac rate, myocardial and left ventricular functions, respiratory rate, blood gases, serum electrolytes and cardiac injury markers were determined before and at 0.5-48 h after endotoxin. Plasma tumor necrosis factor alpha (TNF-alpha), high mobility group box-1 (HMGB1), catecholamine and nitric oxide (NO) levels were measured 2 h and 24 h after the treatments. Endotoxin caused immediate and sustained reductions in blood pressure, cardiac output, pO2 and pH; changes in left ventricular functions, structure and volume parameters; and elevations in heart rate, respiratory rate, pCO2 and serum electrolytes (Na, K, Cl, Ca and P). Endotoxin also resulted in elevations in blood levels of cardiac injury markers, TNF-alpha, HMGB1, catecholamine and NO. In choline- or CDP-choline-treated dogs, all endotoxin effects were much smaller in magnitude and shorter in duration than observed values in controls. These data show that treatment with choline or CDP-choline improves functions of cardiovascular and respiratory systems in experimental endotoxemia and suggest that they may be useful in treatment of endotoxin shock in clinical setting.Item Choline, CDP-choline or phosphocholine increases plasma glucagon in rats: Involvement of the peripheral autonomic nervous system(Elsevier, 2008-07-28) Cansev, Mehmet; İlçöl, Yeşim Özarda; Yılmaz, Mustafa Sertaç; Hamurtekin, Emre; Ulus, İsmail Hakki; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; 0000-0001-9496-1475; 0000-0003-2918-5064; M-9071-2019; AAH-1571-2021; D-5340-2015; AAL-8873-2021; 8872816100; 35741320500; 8895544100; 8717648500; 7004271086The present study was designed to test the effects of choline, cytidine-5'-diphosphocholine (CDP-choline) and phosphocholine on plasma glucagon concentrations in rats. Intraperitoneal (i.p.) injection of 200-600 mu mol/kg of choline, CDP-choline or phosphocholine produced a dose-dependent increase in plasma glucagon and choline concentrations. Pretreatment with hexamethonium (15 mg/kg: i.p.), a peripherally-acting ganglionic nicotinic acetylcholine receptor antagonist, entirely blocked the increases in plasma glucagon by 600 mu mol/kg of choline, CDP-choline or phosphocholine. The increases in plasma glucagon by these choline compounds was reduced significantly (P<0.01) by about 25% by pretreatment with atropine methylnitrate (2 mg/kg), a peripherally-acting muscarinic acetylcholine receptor antagonist. Blockade of central acetylcholine receptors did not alter the increase in plasma glucagon induced by i.p. choline (600 mu mol/kg). While alpha(2)-adrenoceptor blockade or bilateral adrenalectomy attenuated the increase in plasma glucagon evoked by choline compounds, blockade of alpha(1)- or beta-adrenoceptors or chemical sympathectomy failed to alter this increase. Intracerebroventricular (i.c.v.) choline (1.5 mu mol) administration also increased plasma glucagon; the effect was blocked by central pretreatment with a neuronal type nicotinic acetylcholine receptor antagonist, mecamylamine (50 mu g; i.c.v.) or the neuronal choline uptake inhibitor, hemicholinium-3 (20 mu g; i.c.v.). These data show that choline, CDP-choline or phosphocholine increases plasma glucagon concentrations by increasing peripheral nicotinic and muscarinic cholinergic neurotransmissions. Central choline also increases plasma glucagon by augmenting central nicotinic cholinergic neurotransmission by acting presynaptically. Stimulation of adrenal medullary catecholamine release and subsequent activation of alpha(2)-adrenoceptors are mainly involved in the increase in plasma glucagon induced by choline, CDP-choline or phosphocholine.Item Chronic administration of docosahexaenoic acid or eicosapentaenoic acid, but not arachidonic acid, alone or in combination with uridine, increases brain phosphatide and synaptic protein levels in gerbils(Pergemon-Elsevier Science, 2007-08-24) Wurtman, Richard; Cansev, Mehmet; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı.; 0000-0003-2918-5064; M-9071-2019; 8872816100Synthesis of phosphatidylcholine, the most abundant brain membrane phosphatide, requires three circulating precursors: choline; a pyrimidine (e.g. uridine); and a polyunsaturated fatty acid. Supplementing a choline-containing diet with the uridine source uridine-5 '-monophosphate (UMP) or, especially, with UMP plus the omega-3 fatty acid docosahexaenoic acid (given by gavage), produces substantial increases in membrane phosphatide and synaptic protein levels within gerbil brain. We now compare the effects of various polyunsaturated fatty acids, given alone or with UMP, on these synaptic membrane constituents. Gerbils received, daily for 4 weeks, a diet containing choline chloride with or without UMP and/or, by gavage, an omega-3 (docosahexaenoic or eicosapentaenoic acid) or omega-6 (arachidonic acid) fatty acid. Both of the omega-3 fatty acids elevated major brain phosphatide levels (by 18-28%, and 21-27%) and giving UMP along with them enhanced their effects significantly. Arachidonic acid, given alone or with UMP, was without effect. After UMP plus docosahexaenoic acid treatment, total brain phospholipid levels and those of each individual phosphatide increased significantly in all brain regions examined (cortex, striatum, hippocampus, brain stem, and cerebellum). The increases in brain phosphatides in gerbils receiving an omega-3 (but not omega-6) fatty acid, with or without UMP, were accompanied by parallel elevations in levels of pre- and post-synaptic proteins (syntaxin-3, PSD-95 and synapsin-1) but not in those of a ubiquitous structural protein, beta-tubulin. Hence administering omega-3 polyunsaturated fatty acids can enhance synaptic membrane levels in gerbils, and may do so in patients with neurodegenerative diseases, especially when given with a uridine source, while the omega-6 polyunsaturated fatty acid arachidonic acid is ineffective.Item Cytidine 5 '-diphosphocholine ameliorates hyperoxic lung injury in a neonatal rat model(Springernature, 2013-07) Çetinkaya, Merih; Tayman, Cüneyt; Çekmez, Ferhat; Canpolat, Fuat Emre; Tunç, Turan; Sarıcı, S. Ümit; Cansev, Mehmet; Kafa, İlker Mustafa; Uludağ Üniversitesi/Tıp Fakültesi/Anatomi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; M-9071-2019; AAG-7125-2021; 8872816100; 8450193200BACKGROUND: Bronchopulmonary dysplasia (BPD) is an important cause of morbidity. The aim of this study was to evaluate the preventive effect of cytidine 5'-diphosphocholine (CDP-choline) treatment on hyperoxic lung injury in a neonatal rat model. METHODS: A total of 30 newborn pups were divided into control, hyperoxia, and hyperoxia + CDP-choline groups. After birth, pups in the control group were kept in room air and received saline injections, whereas those in hyperoxia and hyperoxia + CDP-choline groups were exposed to 95% O-2 and received daily injections of saline and CDP-choline throughout postnatal day 10, respectively. Histopathological scoring, radial alveolar count, lamellar body membrane protein expression, fibrosis, proinflammatory cytokine levels, lung tissue and bronchoalveolar lavage (BAL) fluid phospholipid content, and apoptosis were evaluated. RESULTS: Hyperoxia-induced severe lung damage was reduced significantly by CDP-choline treatment. Radial alveolar count and lamellar body membrane protein expression were significantly recovered, and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive cells, active caspase-3 expression, and tissue proinflammatory cytokine levels were decreased by CDP-choline administration. Lung tissue and BAL phospholipid contents showed significant increases after COP-choline administration. CONCLUSION: These data show that COP-choline ameliorates hyperoxic lung injury in a neonatal rat model. It may therefore be suggested that CDP-choline may be a novel therapeutic option for the prevention of BPD.Item Cytidine and uridine increase striatal CDP-choline levels without decreasing acetylcholine synthesis or release(Springer/Plenum Publishers, 2006) Watkins, Carol J.; Wurtman, Richard J.; Ulus, İsmail Hakkı; Cansev, Mehmet; Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji ve Klinik Farmakoloji Anabilim Dalı.; 0000-0003-2918-5064; M-9071-2019; D-5340-2015; 7004271086; 8872816100Aims: Treatments that increase acetylcholine release from brain slices decrease the synthesis of phosphatidylcholine by, and its levels in, the slices. We examined whether adding cytidine or uridine to the slice medium, which increases the utilization of choline to form phospholipids, also decreases acetylcholine levels and release. Methods: We incubated rat brain slices with or without cytidine or uridine (both 25400 mu M), and with or without choline (20-40 mu M), and measured the spontaneous and potassium-evoked release of acetylcholine. Results: Striatal slices stimulated for 2 h released 2650 +/- 365 pmol of acetylcholine per mg protein when incubated without choline, or 4600 +/- 450 pmol/mg protein acetylcholine when incubated with choline (20 mu M). Adding cytidine or uridine (both 25-400 mu M) to the media failed to affect acetylcholine release whether or not choline was also added, even though the pyrimidines (400 mu M) did enhance choline's utilization to form CDP-choline by 89 or 61%, respectively. The pyrimidines also had no effect on acetylcholine release from hippocampal and cortical slices. Cytidine or uridine also failed to affect acetylcholine levels in striatal slices, nor choline transport into striatal synaptosomes. Conclusion: These data show that cytidine and uridine can stimulate brain phosphatide synthesis without diminishing acetylcholine synthesis or release.Publication Deneysel şizofreni modelinde bilişsel fonksiyonlar ve hipokampal sinaptofizin düzeylerinin incelenmesi(Bursa Uludağ Üniversitesi, 2023-12-01) Makinecioğlu , İbrahim; Vural , Ayşe Pınar; Ermiş, Erkan; Koç, Cansu; Mergen, Hilmiye Şule; Cansev, Mehmet; Göktalay , Gökhan; Çamlı, Şafak Eray; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Farmakoloji Anabilim Dal.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Çocuk ve Ergen Ruh Sağlığı ve Hastalıkları Anabilim Dalı.; 0000-0001-5359-3477; 0000-0002-6097-5585; 0000-0001-7589-2013; 0000-0003-2918-5064; 0000-0001-6261-4233; 0000-0002-4847-7751Şizofreni pozitif, negatif ve bilişsel belirtiler ile seyreden kronik bir beyin hastalığıdır. Bilişsel belirtiler hastalığın prodromal döneminden itibaren gözlenebilmektedir. Bu çalışmanın amacı irkilme refleksininin ön uyaran aracılı inhibisyonu (ÖUAİ) ile oluşturulan deneysel şizofreni modelinde sıçanların bilişsel fonksiyonlarını ve hipokampal presinaptik proteinlerden sinaptofizin düzeylerini araştırmaktır. Çalışmada 30 adet erkek Wistar türü sıçanlar bazal ÖUAİ ölçümüne tabi tutulmuş ve bu değerlere göre düşükten yükseğe sıralanmıştır. İlk 10 sıçan “düşük” ve son 10 sıçan “yüksek” inhibisyonlu grup olarak ayrıldıktan sonra 5 gün boyunca Morris Su Tankı (MST) testine tabi tutulmuştur. Testin bitiminde sıçanlar sakrifiye edilerek hipokampus bölgeleri eksize edilmiş ve hipokampal presinaptik proteinlerden sinaptofizin Western Blot yöntemiyle analiz edilmiştir. Sonuçlara göre her iki grubun öğrenme düzeyleri arasında fark bulunmaz iken ve hafıza fonksiyonlarının platform alanından geçme sıklığı (p<0,05) ve platform alanında geçirilen süre parametreleri (p<0,05) düşük ÖUAİ gruptaki sıçanlarda anlamlı olarak daha düşük bulunmuştur. Sinaptofizin düzeyleri de benzer şekilde düşük ÖUAİ grubundaki sıçanlarda anlamlı olarak (p<0,01) düşük tespit edilmiştir. Çalışmamızın sonuçları yüksek ÖUAİ değerine sahip sıçanlarla kıyaslandığında ÖUAİ değerleri düşük olan sıçanların bazı bilişsel fonksiyonlarının ve hipokampal presinaptik proteinlerden sinaptofizin düzeylerinin anlamlı olarak daha düşük olduğunu göstermektedir. Bu sonuçlar aynı zamanda uzun zamandır şizofreni çalışmalarında güvenilir bir yöntem olarak kullanılan ÖUAİ testinin insan ve hayvan çalışmalarındaki benzer sonuçlarına vurgu yaparak şizofreni araştırmalarındaki önemini desteklemiştir.Item Deneysel travmatik beyin hasarında üridin ve terapötik hipotermi kombinasyonunun olası koruyucu etkinliğinin araştırılması(Bursa Uludağ Üniversitesi, 2022-05-13) Durak, Vahide Aslıhan; Alkan, Tülin; Cansev, Mehmet; Bursa Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0003-0836-7862Travmatik beyin hasarı dünya çapında morbidite ve mortalitesi yüksek bir acil durumdur. Hastaneye başvuran hastaların çoğuna hafif travmatik beyin hasarı tanısı konmakla birlikte hastalarda uzun dönemde kalıcı hasarlar bırakabilmektedir. Travmatik beyin hasarı fizyopatolojik süreçlerinde birbirini takip eden; primer hasar ve sekonder hasar dönemi yer almaktadır. Primer beyin hasarı travmadan hemen sonra oluşmakta iken sekonder hasar primer hasardan sonra saatler ve günler sonra ortaya çıkmkatadır. Çalışmamızın amacı; deneysel olarak travmatik beyin hasarı modeli uygulaması ile sekonder hasar dönemi ile ilişkili oksidatif, inflamatuar ve apoptotik parametrelerde meydana gelen değişiklikleri incelemek ve Üridin ve/veya hipotermi kombine tedavisinin nöroprotektif etkisini araştırmaktır. Çalışmamızda, Marmarou ve arkadaşlarının tanımladığı serbest ağırlık düşürme modeli kullanılarak travmatik beyin hasarı oluşturulmuş ve hafif hipotermi (32-34.0±1°C) 4 saat boyunca uygulanmıştır. Üridin travmatik beyin hasarını takiben 7 gün boyunca 500mg/kg intraperitoneal uygulanmıştır. Takiben beyin dokusu analizleri, TTC, Western Blot ve ELISA kitleri kullanılarak yapılmıştır. Oksidatif parametreler içerisinden Glutatyon Peroksidaz kombine tedavi uygulaması ile artarken, Katalaz ve Myeloperoksidaz azalmıştır. İnflamatuar belirteçlerden olan İnterlökin-1β ve İnterlökin-6 ise kombine tedavi uygulaması ile azalma göstermiştir. Nekrotik süreçte görev alan Poli ADP-riboz polimeraz-1 ise TBH sonrası artarken, hipotermi, üridin ve kombine tedavi uygulaması ile azalmıştır. Travmatik beyin hasarına yaklaşımda esas hedef sekonder hasar döneminde oluşan etkilere karşı hastayı korumak olup çalışmamızda Üridin-hipotermi kombinasyon tedavisinin etkinliği yedi günlük tedavi uygulaması sonrasında gösterilmiş olup bu açıdan literatürde ilk olma özelliği taşımaktadır. Bu alanda yapılacak diğer çalışmalar ile hafif travmatik beyin hasarında rutin uygulamada kullanılabilecek bir tedavi yaklaşımı olması ve travma hastasının yönetimi kılavuzlarında yer alması hedeflenmektedir. Travmatik beyin hasarı dünya çapında morbidite ve mortalitesi yüksek bir acil durumdur. Hastaneye başvuran hastaların çoğuna hafif travmatik beyin hasarı tanısı konmakla birlikte hastalarda uzun dönemde kalıcı hasarlar bırakabilmektedir. Travmatik beyin hasarı fizyopatolojik süreçlerinde birbirini takip eden; primer hasar ve sekonder hasar dönemi yer almaktadır. Primer beyin hasarı travmadan hemen sonra oluşmakta iken sekonder hasar primer hasardan sonra saatler ve günler sonra ortaya çıkmkatadır. Çalışmamızın amacı; deneysel olarak travmatik beyin hasarı modeli uygulaması ile sekonder hasar dönemi ile ilişkili oksidatif, inflamatuar ve apoptotik parametrelerde meydana gelen değişiklikleri incelemek ve Üridin ve/veya hipotermi kombine tedavisinin nöroprotektif etkisini araştırmaktır. Çalışmamızda, Marmarou ve arkadaşlarının tanımladığı serbest ağırlık düşürme modeli kullanılarak travmatik beyin hasarı oluşturulmuş ve hafif hipotermi (32-34.0±1°C) 4 saat boyunca uygulanmıştır. Üridin travmatik beyin hasarını takiben 7 gün boyunca 500mg/kg intraperitoneal uygulanmıştır. Takiben beyin dokusu analizleri, TTC, Western Blot ve ELISA kitleri kullanılarak yapılmıştır. Oksidatif parametreler içerisinden Glutatyon Peroksidaz kombine tedavi uygulaması ile artarken, Katalaz ve Myeloperoksidaz azalmıştır. İnflamatuar belirteçlerden olan İnterlökin-1β ve İnterlökin-6 ise kombine tedavi uygulaması ile azalma göstermiştir. Nekrotik süreçte görev alan Poli ADP-riboz polimeraz-1 ise TBH sonrası artarken, hipotermi, üridin ve kombine tedavi uygulaması ile azalmıştır. Travmatik beyin hasarına yaklaşımda esas hedef sekonder hasar döneminde oluşan etkilere karşı hastayı korumak olup çalışmamızda Üridin-hipotermi kombinasyon tedavisinin etkinliği yedi günlük tedavi uygulaması sonrasında gösterilmiş olup bu açıdan literatürde ilk olma özelliği taşımaktadır. Bu alanda yapılacak diğer çalışmalar ile hafif travmatik beyin hasarında rutin uygulamada kullanılabilecek bir tedavi yaklaşımı olması ve travma hastasının yönetimi kılavuzlarında yer alması hedeflenmektedir.Item Dietary crude lecithin increases systemic availability of dietary docosahexaenoic acid with combined intake in rats(Wiley, 2016-02-29) van Wijk, Nick; Balvers, Martin; Maher, Timothy J.; Sijben, John W. C.; Broersen, Laus M.; Cansev, Mehmet; Uludağ Üniversitesi/Tıp Fakültesi/Eczacılık Anabilim Dalı.; 0000-0003-2918-5064; M-9071-2019; 8872816100Crude lecithin, a mixture of mainly phospholipids, potentially helps to increase the systemic availability of dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), such as docosahexaenoic acid (DHA). Nevertheless, no clear data exist on the effects of prolonged combined dietary supplementation of DHA and lecithin on RBC and plasma PUFA levels. In the current experiments, levels of DHA and choline, two dietary ingredients that enhance neuronal membrane formation and function, were determined in plasma and red blood cells (RBC) from rats after dietary supplementation of DHA-containing oils with and without concomitant dietary supplementation of crude lecithin for 2-3 weeks. The aim was to provide experimental evidence for the hypothesized additive effects of dietary lecithin (not containing any DHA) on top of dietary DHA on PUFA levels in plasma and RBC. Dietary supplementation of DHA-containing oils, either as vegetable algae oil or as fish oil, increased DHA, eicosapentaenoic acid (EPA), and total n-3 PUFA, and decreased total omega-6 PUFA levels in plasma and RBC, while dietary lecithin supplementation alone did not affect these levels. However, combined dietary supplementation of DHA and lecithin increased the changes induced by DHA supplementation alone. Animals receiving a lecithin-containing diet also had a higher plasma free choline concentration as compared to controls. In conclusion, dietary DHA-containing oils and crude lecithin have synergistic effects on increasing plasma and RBC n-3 PUFA levels, including DHA and EPA. By increasing the systemic availability of dietary DHA, dietary lecithin may increase the efficacy of DHA supplementation when their intake is combined.