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    ASSESSMENT OF THE CARDIOTOXICITY OF TULATHROMYCIN IN RABBITS
    (Akademiai Kiado Zrt, 2011) Er, Ayse; Altan, Feray; Cetin, Gul; Dik, Burak; Elmas, Muammer; Yazar, Enver
    The aim of this study was to determine the cardiotoxic potency of tulathromycin. Tulathromycin (10 mg/kg, SC) was administered to ten adult male rabbits, and blood samples were obtained before and after drug administration (0 and 6 hours). Serum cardiac damage markers (troponin I, creatine kinase-MB, myoglobin, lactate dehydrogenase, aspartate aminotransferase), routine serum biochemical values (alkaline phosphatase, alanine aminotransferase, gammaglutamyltransferase, creatinine, blood urea nitrogen, cholesterol, triglyceride, high-density lipoprotein, amylase, total protein, albumin, glucose, calcium, ionised calcium, sodium, potassium), white blood cell (WBC) and red blood cell (RBC) counts, arterial blood gas parameters (pH, partial carbon dioxide pressure, partial oxygen pressure, actual bicarbonate, standard bicarbonate, total carbon dioxide, base excess in vivo, base excess in vitro, oxygen saturation, packed cell volume, haemoglobin) and serum oxidative status (malondialdehyde, nitric oxide, superoxide dismutase, retinol, beta-carotene) were measured. Increased levels of troponin I, creatine kinase-MB and creatinine, and decreased WBC counts, ionised calcium and potassium levels were observed after drug administration. Tulathromycin treatment may cause cardiotoxicity, but its effects may be less dramatic than those of other macrolide antibiotics frequently used in veterinary medicine.
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    Assessment of the protective effects of pomegranate peel extract and N-acetyl cysteine alone or in combination with Ornipural® against Cadmium-induced bone toxicity in rat
    (2024) Hatipoglu, Durmus; Demircioglu, İsmail; Filikci, Kursat; Korkmaz, Yasemin; Gungor, Huseyin; Demircioglu, Muhammed; Dik, Burak
    Aim: The present study was conducted to determine the effects of pomegranate peel extract (PPE) and N-acetyl Cysteine (NAC) alone or in their treatment combinations with commercial preparation Ornipural® (ORN) on bone metabolism against experimentally cadmium (Cd)-induced toxicity in rats. Materials and Methods: Totally 36 animals were used in the study including 6 Wistar Albino rats in each group. The animals were assigned to control, Cd, Cd+PPE, Cd+NAC, Cd+PPE+ORN and Cd+NAC+ORN groups. The animals in the groups were euthanized after their blood samples were taken at the end of the 8th week. The bones were subjected to maceration for morphometric and histopathological examinations after euthanasia. Results: The statistically significant differences were determined between the treatment groups and Cd group in terms of histopathological changes (osteoporotic alterations and changes in red bone marrow) and biomarkers (Ca, P and Mg) (P<0.05). Conclusion: Although PPE, NAC and treatment combinations with ORN applied against experimentally induced cadmium toxicity were determined to have positive effects on bone metabolism, it has been thought that carrying out trials by increasing treatment duration and dose would be beneficial to determine definite efficacy of the applied treatment protocols.
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    Cardiac Safety of Diclofenac at a Single Dose in Ram
    (Hindawi Ltd, 2013) Er, Ayse; Dik, Burak; Corum, Orhan; Cetin, Gul
    Nonsteroidal anti-inflammatory drugs are frequently prescribed drug group in human and veterinary medicine. However, diclofenac, a traditional nonsteroidal anti-inflammatory drug, related to cardiotoxicity is reported, and blood cardiac damage markers may increase within the first hours after damage. The aim of the current research was to determine the effect of diclofenac on the blood cardiac damage markers. Single dose of diclofenac (2.5mg/kg, IM) was injected to 6 rams. Blood samples were collected in before (0 hour, control) and 6 hours after injection. Specific (troponin I, and creatine kinase-MB) and nonspecific (lactate dehydrogenase, aspartate aminotransferase) blood cardiac damage marker concentrations, routine biochemical (hepatic damage, renal damage, lipid metabolism, glucose, and phosphorus) parameters, and hemogram values were measured. Diclofenac increased (P < 0.05) specific (troponin I) and nonspecific cardiac (lactate dehydrogenase, aspartate aminotransferase), hepatic (aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase), andmuscular (creatine kinase) damagemarkers and high density lipoprotein level, while it decreased (P < 0.05) low density lipoprotein level. Moreover, diclofenac decreased (P < 0.05) white blood cell counts and increased (P < 0.05) red blood cell counts. In conclusion, it may be stated that diclofenac shows slight cardiotoxicity, whereas it may show potent hepatic and muscular damage effects at an intramuscularly single dose in sheep. Thereby, repeated injections of diclofenac may be more harmful in sheep.
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    Doksorubisinin neden olduğu organ hasarlarında Nerium oleander distilatının koruyucu etkinliğinin belirlenmesi
    (2014) Er, Ayşe; Çorum, Orhan; Dik, Burak
    Amaç: Araştırmanın amacı doksorubisinin neden olduğu oksidatif hasar ve diğer yan etkilere Nerium oleander (NO) distilatının etkisini araştırmaktır.Gereç ve Yöntem: NO yaprakları toplandıktan sonra distilasyonu yapılarak liyofilize edildi. Araştırmada 28 adet rat, Kontrol, Doksorubisin (3 mg/kg, iki günde bir peritoniçi, 6 uygulama), NO (1 mg/kg/gün, oral) ve Doksorubisin (3 mg/kg, iki günde bir peritoniçi, 6 uygulama) + NO (1 mg/kg/gün, oral) olmak üzere 4 gruba ayrıldı ve uygulamalar 11 gün süresince yapıldı. Son uygulamadan 24 saat sonra anestezi altındaki ratların kalplerinden kan alındı ve hemen ötenazi edildi. Ayrıca kalp, karaciğer ve böbrek organları alınarak homojenize edildi. Organ tiobarbiturik asit türevi reaktif maddeler (TBARS) düzeyleri ELISA, serum biyokimyasal değerleri otoanalizörle ve tam kan değerleri kan hücresi sayım cihazında belirlendi.Bulgular: Doksorubisin grubunun böbrek TBARS değeri NO distilatı grubundan yüksek (P<0.05) belirlenirken, Doksorubisin grubunun kalp TBARS değeri Doksorubisin + NO distilatı grubundan düşük (P<0.05) belirlendi. Doksorubisin uygulamasının kan hücreleri sayıları, hemoglobin ve hematokrit düzeylerini Kontrol grubuna göre düşürdüğü (P<0.05), Doksorubisin + NO distilatı uygulamasının sadece hematokrit değerini yükselttiği belirlendi. Doksorubisin uygulamasının serum total protein ile albümin düzeylerini Kontrol grubuna göre düşürdüğü (P<0.05), Doksorubisin + NO distilatı uygulamasının Kontrol grubuna göre aspartat aminotransferaz ile kan üre nitrojen değerlerini yükselttiği (P<0.05) ve total protein, albümin ile kreatinin değerlerini düşürdüğü (P<0.05) belirlendi.Öneri: Mevcut araştırmada kullanılan NO distilatı düzeyinin, doksorubisinin neden olduğu istenmeyen etkileri engellemede belirgin etkisinin olmadığı ifade edilebilir.
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    Effect of Corynebacterium cutis Lysate on Serum Oxidative Stress and Plasma Prostaglandin F2? Metabolite Levels
    (Univ Fed Rio Grande Do Sul, 2014) Er, Ayse; Dik, Burak; Corum, Orhan
    Background: The Corynebacterium cutis lysate is commercial product. Unbalance between oxidants and antioxidants cause oxidative stress and lipid peroxidation in the cell. Macrophages phagocytose large pieces of bacteria and synthesize cytokines. In addition to the benefi cial results of the drug have side effects. Since changes in biochemical parameters refl ect structural dysfunction in the organism, monitoring changes of these parameters is a way to keep track of side effects. The aim of this study was to determine the effect of Corynebacterium cutis lysate on serum thiobarbituric acid-reactive substances (TBARS) and plasma 13,14-dihydro-15-keto-prostaglandinF2a (PGM) levels in sheep. Materials, Methods & Results: Six Merino crossbred ewes (aged > 2 years, weight 40-60 kg) were used in this study. The procedures were approved by the Ethics Committee. A dose of 8 mg (0.4 mL) of commercial Corynebacterium cutis lysate was subcutaneously injected to each of the 6 Merino crossbred ewes. Blood specimens were taken from the sheep prior to injection (day 0, control) and after the injection on days 1, 2, 3, and 4. The levels of serum TBARS and plasma PGM were determined using an Enzyme Linked Immunosorbent Assay (ELISA) reader. The values of the hemogram [ white blood cells (WBC), red blood cells (RBC), platelets (PLT), hematocrit (HTC), and hemoglobin (HBG)] were assessed using a blood cell count apparatus. The levels of plasma creatine kinase-MB (CK-MB), serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), total protein (TP), albumin (ALB), blood urea nitrogen (BUN), creatinine, and cholesterol were determined on an autoanalyzer. The data obtained were analyzed using ANOVA and Scheffe's test as a post hoc test (SPSS 19.0). A P < 0.05 value was taken as the cut-off value for statistical signifi cance. An increase (P < 0.05) in the levels of plasma PGM and serum cholesterol was detected when compared to the control samples, but there was no statistically signifi cant (P > 0.05) change in the other parameters. Discussion: The Corynebacterium cutis lysate is a commercial product and used in cattle, newborn calves, sheep, and poultry as an immunostimulant against infections and to increase body resistance in times of stress. Corynebacterium cutis lysate increased (P < 0.05) in plasma PGM and serum cholesterol levels compared to the control group. Detailed studies dealing with the effect of Corynebacterium cutis lysate on PGM and TBARS are not available in the literature. There is a balance between oxidants and antioxidants in the organism. Unbalance between oxidants and antioxidants caused by increased production of oxidizing species leads to oxidative stress and lipid peroxidation in the cells. The levels of TBARS or malondialdehyde are used in order to determine lipid peroxidation. The levels of serum TBARS, malondialdehyde and PGM increased in experimental infection models. Macrophages phagocytose large pieces of bacteria such as Corynebacterium cutis lysate and this case triggers the synthesis of cytokines by macrophages. Cholesterol metabolism may change in infections, and high levels of cholesterol were determined in test subjects after injection of LPS. Lipid metabolism may be affected by stimulants of the immune system, such as Corynebacterium cutis lysate. In conclusion, Corynebacterium cutis lysate has no effect on the oxidative status and number of blood cells and organ (heart, liver and kidney) damage markers in sheep and it may increase plasma PGM level by stimulating the immune system.
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    Effects of BCRP and P-gp modulators on the penetration of aflatoxin B1 into the mouse brain
    (Kafkas Üniversitesi Veteriner Fakültesi, 2017) Traş, Bünyamin; Çetin, Gül; Üney, Kamil; Çorum, Orhan; Atalay, Sema; Dik, Burak
    This study was conducted to determine whether the plasma and brain concentrations of AFB1 are affected by the modulation of P-gp and BCRP using zosuquidar (ZQR) and prazosin (PRZ), respectively. In this study, a total of 40 healthy adult male BALB/c mice (32±3.7 g) were used. The animals were randomly divided into 5 groups, with 8 animals per group. Group 1 was used for method validation. Group 2 (AF) received intraperitoneal AFB1 at a dose of 20 mg/kg of body weight. Groups 3 (AF+PRZ), 4 (AF+ZQR), and 5 (AF+PRZ+ZQR) received 20 mg/kg of AFB1 intraperitoneally 30 min after the intraperitoneal administration of prazosin (0.3 mg/kg), zosuquidar (25 mg/kg), and prazosin+zosuquidar (0.3 mg/kg prazosin + 25 mg/kg zosuquidar), respectively. Six hours after the administration of AFB1, blood and brain samples were collected from the animals in Groups 2 to 5. AFB1 concentrations were determined using an HPLC system with fluorescence detection. Individual and simultaneous administration of prazosin and zosuquidar significantly reduced the brain concentrations of AFB1 in comparison to a single administration of AFB1 (P<0.05). The brain/plasma ratio of the AF group was higher than that of the other groups (AF+PRZ, AF+ZQR, and AF+PRZ+ZQR) (P<0.05). Inducers of transmembrane proteins, especially BCRP, can be life saving during acute AFB1 poisoning.
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    Etanersept - endotoksemi tedavisinde kullanılabilir mi?
    (Kafkas Üniversitesi Veteriner Fakültesi, 2013) Er, Ayşe; Dik, Burak; Çetin, Gül; Altan, Feray; Üney, Kamil; Elmas, Muammer; Yazar, Enver
    Araştırmanın amacı endotoksemide etanersept uygulamasının kan sitokinler, fibrinojen, antitrombin, 13,14-dihidro-15-keto prostaglandin F2α ve biyokimyasal parametrelere etkisini araştırmaktır. Erişkin 126 adet Sprague Dawley ırkı erkek rat 3 gruba ayrılarak; 1. Gruba lipopolisakkarit (4 mg, IP), 2. Gruba etanersept (8 mg/kg, IP) ve 3. Gruba lipopolisakkarit + etanersept uygulamaları yapıldı. Uygulamalardan sonra 0., 1., 2., 4., 8., 12. ve 24. saatlerde kan örnekleri alındı. Serum tümör nekrozis faktör-α, interlöykin-1β, interlöykin-10 ve plazma 13,14-dihidro-15-keto-prostaglandin F2α düzeyleri ELISA okuyucusunda; sitratlı plazma antitrombin ve fibrinojen düzeyleri koagulometrede; serum biyokimyasal parametreleri otoanalizörde belirlendi. Etanerseptin fibrinojen düzeyinde düzensiz değişimlere ve 13,14-dihidro15-keto-prostaglandin F2α, alkalen fosfataz ile alanin aminotransferaz düzeyinde yükselmelere neden olduğu belirlendi. Lipopolisakkarit uygulaması sitokinler, 13,14-dihidro-15-keto-prostaglandin F2α, fibrinojen, organ hasar belirteçleri ve trigliserit düzeylerinde yükselmelere neden olurken, antitrombin seviyesinde düzensiz değişimlere neden oldu. Lipopolisakkarit + etanersept uygulanan grupta sitokinler, 13,14-dihidro-15-keto-prostaglandin F2α ve fibrinojen düzeyinde yükselmeler, antirombin düzeyinde düzensiz değişimler gözlendi. Lipopolisakkarit uygulaması ile yükselen kreatin kinaz-MB düzeyinin etanersept tarafından tamamen, tümör nekrozis faktör-α yükselmesinin kısmen engellendiği ancak kanda kalış süresini uzattığı ve interlöykin-10 düzeyini daha fazla yükselttiği belirlendi. Sonuç olarak endotoksemide etanerseptin kalp üzerindeki koruyucu etkisi ve interlöykin-10 düzeyini yükseltmesi nedeni ile tek doz uygulamasının veteriner sahada faydalı olabileceği belirlendi.
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    Investigation of the Effect of Tarantula cubensis Extract on Acute Phase Response
    (Univ Fed Rio Grande Do Sul, 2016) Corum, Orhan; Er, Ayse; Dik, Burak
    Background: Tarantula cubensis alcoholic extract is used to accelerate wound healing and to relieve edema in many animal species. In addition, it may be useful for many infectious diseases. Considering to these effects, it is believe that these effects may be on immune system. Cytokines (tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10 and interferon gamma) secreted by immune cells and acute phase proteins (haptoglobin, alpha 1 acid glycoprotein, serum amyloid A) secreted by liver play role in acute phase response. The aim of the present study was to determine the effect of Tarantula cubensis alcoholic extract on cytokine and acute phase protein levels in sheep. Materials, Methods & Results: Tarantula cubensis alcoholic extract (6 mL/sheep, subcutaneously, single dose) was administered to 6 healthy sheep. Blood samples were obtained before (0 h) and after treatments at 2, 4, 8, 12, 24 and 48 h. Then, blood samples were centrifuged to obtain serum samples. Acute phase cytokines such as serum tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10, interferon gamma and acute phase proteins such as haptoglobin, alpha 1 acid glycoprotein and serum amyloid-A concentrations were determined with commercially available kits on ELISA reader. Administration of Tarantula cubensis alcoholic extract caused fluctuations in tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10, interferon gamma levels in sheep. In addition, levels of haptoglobin, alpha 1 acid glycoprotein, serum amyloid A showed fluctuations. But, these fluctuations in acute phase cytokines and acute phase proteins were not statistically significant (P > 0.05). Discussion: Tarantula cubensis alcoholic extract, homeopathic medicine, is used trauma, retentio secundinarium, tendinitis, bluetongue, foot and mouth, metritis and arthritis in many animal species including sheep. Cytokines, secreted against various stimulus including infectious diseases, play role in wound healing and in the regulation of the immune system. In current study, administration of Tarantula cubensis alcoholic extract lead to fluctuations in tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10 and interferon gamma levels, but these changes were not statistically significant (P > 0.05). Non-statistical fluctuations in cytokines result from inadequate immunological response of sheep against to Tarantula cubensis alcoholic extract. Also, use of molecular analysis techniques may be changed these results. Acute phase proteins are significantly secreted from the liver during the acute phase response. In current study, administration of Tarantula cubensis alcoholic extract in sheep caused non-statistifical fluctuations on haptoglobin, alpha 1 acid glycoprotein and serum amyloid A levels (P > 0.05). Tumor necrosis factor alpha and interleukin-1 beta stimulate synthesis of interleukin-6. Interleukin-6 provides synthesis of acute phase proteins in liver. Non-statistical fluctuations in acute phase proteins result from inadequate stimulus of IL-6. In conclusion, it may be stated that administration of Tarantula cubensis alcoholic extract has no distinctive effect on the acute phase response. However, when Tarantula cubensis alcoholic extract is administered repeated times or other acute phase parameters are evaluated, different results may be observed.
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    Koyunlara Corynebacterium cutis lizatı uygulamasının serum sitokin düzeylerine etkisinin belirlenmesi
    (2015) Eser, Hatice; Dik, Burak; Yazar, Enver; Bahçivan, Emre; Çorum, Orhan; Er, Ayşe
    Amaç: Mevcut araştırmanın amacı koyunlara Corynebacterium cutis lizatı uygulamasının serum sitokin düzeyleri üzerine etkisi ile birlikte hemogram ve rutin biyokimyasal parametrelere etkisini belirlemektir. Gereç ve Yöntem: Araştırmada 10 adet erkek Merinos toklu kullanıldı. Her bir hayvana önerilen dozda (8 mg, 0.4 mL) Corynebacterium cutis lizatı (Ultra-corn® Inj. Susp.) subkutan yolla bir kez uygulandı. Uygulamadan önce (0. saat, kontrol) ve sonraki 2, 4, 8, 12, 24, 48, 72 ve 96. saatlerde v. jugularisten kan örnekleri alındı. Elde edilen serumlardan tümör nekrozis faktör alfa (TNF?), interlöykin (IL)-1?, IL-6 ve IL-10 düzeyleri ELISA okuyucusunda belirlendi. Hemogram değerleri (Alyuvar, akyuvar, platelet, hematokrit, hemoglobin) kan hücresi sayım cihazında ve biyokimyasal (Kreatin kinaz-MB, alkalen fosfataz, alanin aminotransferaz, aspartat aminotransferaz, gamma glutamiltransferaz, total protein, albümin, kan üre nitrojen, kreatinin) değerler otoanalizörde ölçüldü. Bulgular: Corynebacterium cutis lizatı uygulamasının sitokin düzeylerinde dalgalanmalara neden olduğu gözlendi (P>0.05). Hemogram parametrelerinde istatistiki değişimlere neden olmazken, bazı biyokimyasal değerlerde (Alkalen fosfataz, total protein, albümin, kreatinin) dalgalanmalara neden olduğu tespit edildi (P<0.05). Öneri: Erkek toklulara Corynebacterium cutis lizatı uygulamasının sitokin düzeyleri üzerine belirgin etkisinin olmadı- ğı, pasif immunite üzerine olan etkilerinin belirlenmesi için daha detaylı araştırmalara gerek duyulduğu ifade edilebilir
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    Koyunlarda Tarantula cubensis alkolik ekstraktının (Theranekron®) serum tiyobarbitürik asit reaktif ürünlerine etkisi
    (2014) Dik, Burak; Er, Ayşe; Çorum, Orhan
    Amaç: Mevcut araştırmanın amacı koyunlarda Tarantula cubensis alkolik ekstraktının serum tiyobarbitürik asit reaktif ürünlerine etkisini değerlendirmektir. Ayrıca hematolojik ve biyokimyasal parametrelere etkilerini değerlendirmektir.Gereç ve Yöntem: Altı adet Akkaraman koyuna tek doz (6 mL/koyun, SC) Tarantula cubensis alkolik ekstraktı uygulandı. Kan örnekleri uygulamadan hemen önce (0 saat, kontrol) ve sonraki 2, 4, 8, 12, 24 ve 48. saatlerde alındı. Serum tiyobarbitürik asit reaktif ürünleri düzeyi ELISA okuyucusunda belirlendi. Biyokimyasal ve hematolojik parametreler sırası ile otoanalizör ve kan hücresi sayım cihazında belirlendi.Bulgular: Tarantula cubensis alkolik ekstraktı koyunlarda serum tiyobarbitürik asit reaktif ürünleri düzeyini belirgin şekilde düşürdü, ancak istatistiki fark belirlenmedi. Ayrıca ekstratın hematolojik ve biyokimyasal parametrelere olumsuz etkisi belirlenmedi.Öneri: Tarantula cubensis alkolik ekstraktının antioksidan etkinlik gösterebileceği ve kısa süreli değerlendirilmesi dikkate alındığında koyunlarda güvenli olabileceği ifade edilebilir.
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    Nerium oleander distilatı uygulamasının serum nitrik oksit düzeyine etkisi
    (Selçuk Üniversitesi Veteriner Fakültesi, 2015) Er, Ayşe; Çorum, Orhan; Çetin, Gül; Dik, Burak
    Amaç: Mevcut araştırmanın amacı ratlara tek doz intraperitonealNerium oleander distilatı uygulamasının serum nitrik oksit düzeyine etkisini araştırmaktır. Ayrıca distilatın tiyobarbitürik asit reaktifürünleri, katalaz ve rutin biyokimyasal parametrelere etkisini belirlemektir. Gereç ve Yöntem: Araştırmada 20 adet erkek Wistar albino rat kullanıldı. Kontrol (0. saat) olarak 5 adet rat ayrıldıktan sonra diğerlerine 7.5 mL Nerium oleander distilatı intraperitoneal olarak tek seferde uygulandı. Uygulama öncesi (0. saat) ve uygulama sonrasında2., 4. ve 8. saatlerde ratlar anesteziye alınarak kalplerinden kan örnekleri alındıktan sonra hayvanlar servikal dislokasyon yöntemiyleötenazi edildi. Serum örneklerinden nitrik oksit, tiyobarbitürik asitreaktif ürünleri ve katalaz düzeyleri ELISA okuyucusunda, biyokimyasal parametreler (Kreatin kinaz-MB, kreatin kinaz, alkalen fosfataz, alanin aminotransferaz, aspartat aminotransferaz, total protein,albümin, total bilirubin, kolesterol, trigliserit, yüksek dansiteli lipoprotein, düşük dansiteli lipoprotein, kreatinin, ürik asit, kan üre nitrojen) ise otoanalizörde belirlendi.Bulgular: Nerium oleander distilatı uygulamasının nitrik oksit düzeyine etkisinin olmadığı (P>0.05), tiyobarbitürik asit reaktif ürünleri düzeylerini düşürdüğü (P<0.05), katalaz düzeyini ise yükselttiği(P<0.05) belirlendi. Ayrıca Nerium oleander uygulamasının total bilirubin düzeyini 2. saatte, düşük dansiteli lipoprotein ve kolesteroldüzeyini 8. saatte yükselttiği (P<0.05) belirlendi.Öneri: Nerium oleander distilatının güçlü antioksidan etkinlik göstererek oksidatif strese bağlı gelişen dejeneratif durumlarda tedaviyedestek amaçlı kullanılabileceği ifade edilebilir.
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    Neuroprotective Effects of Bexarotene and Icariin in a Diabetic Rat Model
    (Springernature, 2024) Agircan, Dilek; Parlak, Tugba Melike; Tufan, Oznur; Demircioglu, Muhammed; Dik, Burak
    Objective Type 2 diabetes mellitus (T2DM), a chronic metabolic disorder affecting over 400 million people globally, is increasingly recognized for its detrimental impact on the central nervous system. T2DM is linked to neurodegenerative diseases like Alzheimer's and vascular dementia. This study investigates the neuroprotective effects of bexarotene and icariin in a T2DM rat model, focusing on brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and neurofilament-light chain (NfL) levels. Methods Before the study, rats underwent fasting blood glucose tests, lipid profile assessments, and general health evaluations, followed by a high-fat diet for two weeks and a single streptozotocin dose (35 mg/kg). Rats with fasting blood glucose levels >= 250 mg/dl were classified as diabetes mellitus (DM) and continued on the high- fat diet throughout the experiment. Forty-seven male Wistar Albino rats were divided into six groups: a healthy control group, a DM control group, a DM group treated with bexarotene, a DM group treated with icariin, and two DM groups treated with combinations of low and high doses of bexarotene and icariin. After the 45-day treatment, blood samples were collected under thiopental sodium anesthesia, with HbA1c (glycosylated hemoglobin) and hematological parameters analyzed within eight hours, and serum stored at- 80 degrees C for further analysis. The animals were then euthanized, and brain tissues were harvested, frozen, and stored at-80 degrees C until further examination. Brain tissues were analyzed for BDNF, GFAP, and NfL levels using ELISA (enzyme-linked immunosorbent assay). For comparing multiple groups, the Kruskal-Wallis test was applied to nonparametric data, and one-way ANOVA was used for parametric data, followed by Bonferroni's post hoc test for pairwise comparisons. Statistical significance was determined with two-tailed tests at p < 0.05. Results Significant changes in GFAP levels were observed across groups (p < 0.001). The DM control group showed the highest GFAP levels, while treatment groups exhibited reductions. The DM control group also showed the highest BDNF levels, while treatment groups exhibited reductions. The DM control group showed the lowest NfL levels, while treatment groups exhibited increments. Conclusion This study highlights the neuroprotective potential of bexarotene and icariin in a diabetic rat model, evidenced by significant changes in GFAP levels. The lack of significant changes in BDNF and NfL suggests that longer study durations may be necessary to observe these effects. Future research should include extended study periods, larger sample sizes, varied dosages, and comprehensive behavioral assessments to better understand the therapeutic potential of these agents.
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    Pharmacokinetics of ceftiofur in healthy and lipopolysaccharide-induced endotoxemic newborn calves treated with single and combined therapy
    (Japan Soc Vet Sci, 2017) Altan, Feray; Uney, Kamil; Er, Ayse; Cetin, Gul; Dik, Burak; Yazar, Enver; Elmas, Muammer
    The aim of this research was to compare plasma pharmacokinetics of ceftiofur sodium (CS) in healthy calves, and in calves with experimentally induced endotoxemia. Six calves received CS (2.2 mg/kg, IM) 2 hr after intravenous administration of 0.9% NaCl (Ceft group). After a washout period, the same 6 calves received CS 2 hr after intravenous injection of lipopolysaccharide (LPS+Ceft group). Another group of 6 calves received a combination of drug therapies that included CS 2 hr after administration of 0.9% NaCl (Comb group). A third group of 6 calves received the same combination therapy regimen 2 hr after intravenous injection of lipopolysaccharide (LPS+Comb group). Plasma concentrations of CS and all desfuroylceftiofurrelated metabolites were determined using HPLC, and its pharmacokinetic properties were determined based on a two-compartment model. The peak concentration of CS in the LPS+Comb group occurred the earliest, and the clearance rate of CS was the highest in the Comb and LPS+ Comb groups (P < 0.05). The elimination half-life of CS in the LPS+Ceft group was longer than that in the Ceft and Comb groups (P < 0.05). The results of this study indicate that combined therapies and endotoxemic status may alter the plasma pharmacokinetics of CS in calves.
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    Öğe
    Pharmacokinetics of meloxicam in red-eared slider turtles (Trachemys scripta elegans) after single intravenous and intramuscular injections
    (Amer Veterinary Medical Assoc, 2016) Uney, Kamil; Altan, Feray; Aboubakr, Mohammed; Cetin, Gul; Dik, Burak
    OBJECTIVE To determine the pharmacokinetics of meloxicam after single IV and IM injections in red-eared slider turtles (Trachemys scripta elegans). ANIMALS 8 healthy red-eared slider turtles. PROCEDURES Turtles received 1 dose of meloxicam (0.2 mg/kg) IV or IM (4 turtles/route), a 30-day washout period was provided, and then turtles received the same dose by the opposite route. Blood samples were collected at predetermined times for measurement of plasma meloxicam concentration. Pharmacokinetic values for each administration route were determined with a 2-compartment open model approach. RESULTS For IV administration, mean +/- SD values of major pharmacokinetic variables were 1.02 +/- 0.41 hours for distribution half-life, 9.78 +/- 2.23 hours for elimination half-life, 215 +/- 32 mL/kg for volume of distribution at steady state, 11.27 +/- 1.44 mu g.h/mL for area under the plasma concentration versus time curve, and 18.00 +/- 2.32 mL/h/kg for total body clearance. For IM administration, mean values were 0.35 +/- 0.06 hours for absorption half-life, 0.72 +/- 0.06 mu g/mL for peak plasma concentration, 1.5 +/- 0.0 hours for time to peak concentration, 3.73 +/- 2.41 hours for distribution half-life, 13.53 +/- 1.95 hours for elimination half-life, 11.33 +/- 0.92 mu g.h/mL for area under the plasma concentration versus time curve, and 101 +/- 6% for bioavailability. No adverse reactions were detected. CONCLUSIONS AND CLINICAL RELEVANCE Long half-life, high bioavailability, and lack of immediate adverse reactions of meloxicam administered IM at 0.2 mg/kg suggested the possibility of safe and effective clinical use in turtles. Additional studies are needed to establish appropriate administration frequency and clinical efficacy.