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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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    Development and validation of a high-performance liquid chromatography method for determination of cefquinome concentrations in sheep plasma and its application to pharmacokinetic studies
    (2011) Üney, Kamil; Altan, Feray; Elmas, Muammer
    Cefquinome has a broad spectrum of antibacterial activity and was developed especially for use in animals. A simple and sensitive high-performance liquid chromatography (HPLC) method with UV-visible detection for quantification of cefquinome concentrations in sheep plasma was developed and validated. Separation of cefquinome from plasma components was achieved on a Phenomenex Gemini C 18 column (250 mm by 4.6 mm; internal diameter [i.d.], 5 μm). The mobile phase consisted of acetonitrile and 0.1% trifluoroacetic acid in water and was delivered at a rate of 0.9 ml/min. A simple and rapid sample preparation involved the addition of methanol to 200 μl of plasma to precipitate plasma proteins followed by direct injection of 50 μl of supernatant into the high-performance liquid chromatography system. The linearity range of the proposed method was 0.02 to 12 μg/ml. The intraday and interday coefficients of variation obtained from cefquinome were less than 5%, and biases ranged from -3.76% to 1.24%. Mean recovery based on low-, medium-, and high-quality control standards ranged between 92.0 and 93.9%. Plasma samples were found to be stable in various storage conditions (freeze-thaw, postpreparative, short-term, and long-term stability). The method described was found to be readily available, practicable, cheap, rapid, sensitive, precise, and accurate. It was successfully applied to the study of the pharmacokinetics of cefquinome in sheep. This method can be very useful and an alternate to performing pharmacokinetic studies in the determination of cefquinome for clinical use.
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    Effect of multiple-dose administration of cefquinome on hematological and biochemical parameters in horse
    (Dicle Üniversitesi Veteriner Fakültesi, 2019) Altan, Feray; Erol, Hanifi; Altan, Semih; Arıcan, Mustafa; Elmas, Muammer; Üney, Kamil
    Sefkuinomun (CFQ) çoklu doz uygulamalarının, atların hematolojik ve biyokimyasal profilleri üzerinde bir etkisi olup olmadığı bilinmemektedir. Bu çalışmanın amacı, atlarda çoklu artan CFQ dozlarının bazı hematolojik (WBC, LYM, MON, GRA, RBC, HB, HT, MCV, MCH, MCHC, RDW ve PLT) ve biyokimyasal parametreler üzerine (ALB, ALP, ALT, AST, CH, CR, GGT, LDH, TB, TP, TRIG ve BUN) etkisini belirlemektir. Araştırma 16 adet erişkin at (4.6 ± 2.1 yaş, 302 ± 38 kg) üzerinde gerçekleştirildi. Atlara damar içi olarak 7 gün boyunca her 12 saatte dört doz seviyesinde CFQ uygulandı: Grup I; 1 mg/kg, Grup II; 2 mg/kg, Grup III; 4 mg/kg, Grup IV; 6 mg/kg) uygulanan toplam 13 enjeksiyon gerçekleştirildi. Belirlenen hematolojik ve biyokimyasal parametreler ilaç uygulamasından önce (0 gün) ve ilk CFQ dozunun uygulanmasından 1, 3, 7 ve 14 gün sonra izlendi. Tedavi günlerinde gruplar arasında serum biyokimyasal parametrelerinde anlamlı bir fark bulunmadı (p> 0.05). Hematolojik parametrelerde (MONO, GRAN, RBC, HB, HCT, MCH ve PCT) doz grupları arasında referans değerler içinde anlamlı farklar bulundu (p <0.05). Bu sonuçlar, atlarda CFQ’un 6 mg/kg kadar çoklu doz uygulamalarının, değerlendirilen kan parametreleri üzerinde klinik olarak önemli bir etkisi olmadığını göstermektedir.
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    Effects of drugs on kinetic values of cytokines, adenosine deaminase and 13,14-dihydro-15-keto-prostaglandin $F_{2alpha}$ in endotoxemia: A different approach
    (2010) Elmas, Muammer; Er, Ayşe; Traş, Bünyamin; Üney, Kamil; Çetin, Gül; Altan, Feray; Yazar, Enver
    Altan F, Elmas M, Er A, Üney K, Çetin G, Traş B, Yazar E. Endotoksemide ilaçların sitokinler, adenozin deaminaz ve 13,14-dihidro-15-keto-prostaglandin F_{2alpha'nın kinetik değerlerine etkisi: Farklı bir yaklaşım. Eurasian J Vet Sci, 2010, 26, 1, 15-19 Amaç: Lipopolisakkaritle (LPS) oluşturulan deneysel endotoksemide sitokinler, adenozin deaminaz (ADA) ve 13,14-dihidro-15-keto-prostaglandin $F_{2alpha}$ (PGM)’nın kinetik değerlerine tek başlarına ve/veya kombine uygulanan enrofloksasin (ENR), fluniksin meglumin (FM) ve deksametazonun (DEX) etkilerini belirlemektir. Gereç ve Yöntem: Araştırmada kullanılan ratlar 7 gruba ayrıldı. Deneysel endotoksemi oluşturmak için pozitif kontrol grubu dahil bütün gruplara LPS uygulandı. Diğer altı gruba ENR, FM, düşük doz DEX, yüksek doz DEX, ENR+FM+düşük doz DEX ve ENR+FM+yüksek doz DEX uygulandı. Uygulama sonrası 0, 1, 2, 4, 6, 8, 12, 24 ve 48. saatlerde kan örnekleri toplandı. Tümör nekroz faktör alfa ($TNF_{alpha}$), interlökin-6 (IL- 6), interlökin-10 (IL-10), ADA ve PGM düzeyleri ELISA ile belirlendi. Eğri altında kalan alan ($EAA_{0-48}$) farmakokinetik programla, plazma veya serum maksimum konsantrasyon ($C_{max}$) ile maksimum konsantrasyona ulaşma zamanı ($t_{max}$) direk bakı yöntemiyle belirlendi. Bulgular: Pozitif kontrol (LPS) grubuyla kıyaslandığında $EAA_{0-48}$ değerlerinin; ENR grubunda PGM için artarken (p<0.05), IL-6, IL-10 ve ADA için azaldığı (p<0.05); FM grubunda IL-6 ve ADA’ya özgü olarak küçüldüğü (p<0.05); DEX tek başına veya kombine uygulandığı gruplarda da azaldığı (p<0.05) belirlendi. Öneri: Farklı örnekleme zamanlarında çok sayıda ölçülen aynı endotoksemi belirteçlerinin toplu değerlendirilmesinde kinetik parametrelerden özellikle EAA’nin farklı ve akılcı bir yaklaşım olarak dikkate alınabileceği kanaatine varıldı.
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    Effects of enrofloxacin, flunixin and dexamethasone on indicators of oxidative and organ damage in lipopolysaccharide-induced endotoxemia
    (2010) Er, Ayşe; Altan, Feray; Çetin, Gül; Üney, Kamil; Traş, Binyamin; Elmas, Muammer; Yazar, Tinver
    The aim of this study was to determine the effects of enrofloxacin, flunixm meglumme and dexamethasone on antioxidant status and markers of organ damage in endotoxemia. Rats were divided into four groups. The groups received the following drugs (simultaneously with lipopolysaccharide): enrofloxacin, flunixin meglumine, low-dose dexamethasone or high-dose dexamethasone, respectively. After the treatments, serum and plasma samples were collected at 1, 2, 4, 6, 8, 12, 24 and 48 h. The levels of malondialdehyde, nitric oxide, superoxide dismutase, vitamin C and 13,14-dihydro-15-keto-prostaglandin F2a were determined with ELISA. The cardiac, hepatic and renal damage markers were measured with autoanalyzer. Elevated levels of malondialdehyde were relatively inhibited by high-dose dexamethasone. Increases in the levels of nitric oxide were inhibited by low and high-dose dexamethasone while increases in the level of 13,14-dihydro-15-keto prostaglandin F2n were inhibited by all treatments except enrofloxacin. No treatments inhibited the decrease in vitamin C levels. Cardiac andhepatic damage was not inhibited completely whereas renal damage was inhibited by treatment with low or high-dose dexamethasone. The results show that although low-dose dexamethasone had antioxidant activity and protected against organ damage, high-dose dexamethasone may be more beneficial in the treatment of endotoxemia.
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    EFFECTS OF TYLOSIN ON SERUM CYTOKINE LEVELS IN HEALTHY AND LIPOPOLYSACCHARIDE-TREATED MICE
    (Akademiai Kiado Zrt, 2010) Er, Ayse; Yazar, Enver; Uney, Kamil; Elmas, Muammer; Altan, Feray; Cetin, Gul
    The effects of different doses of tylosin on serum cytokine concentrations were investigated in healthy and lipopolysaccharide-treated mice. The mice were divided into seven groups. Lipopolysaccharide (LPS) was injected into the positive control group. The other six groups received three different tylosin doses concurrently without or with LPS: 10 mg/kg, 100 mg/kg, 500 mg/kg, 10 mg/kg + LPS, 100 mg/kg + LPS and 500 mg/kg + LPS. After treatment, serum samples were collected at 0, 1, 2, 3, 6, 12 and 24 hours. Serum tumour necrosis factor alpha (TNF alpha), interleukin 1 beta (IL1 beta) and IL10 levels were determined by enzyme-linked immunosorbent assay (ELISA). Tylosin doses of 10 and 100 mg/kg induced no cytokine production in the healthy mice. Tylosin at 500 mg/kg had no effect on TNF alpha or IL1 beta production, but it induced IL10 production in healthy mice. All doses of tylosin reduced the elevated TNF alpha and IL1 beta in LPS-treated mice but increased their IL10 levels. In conclusion, these data suggest that tylosin has an immunomodulatory effect at the dose recommended for use against infection.
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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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    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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    Tulathromycin disturbs blood oxidative and coagulation status
    (Academic Journals, 2011) Er, Ayse; Ulutas, Elmas; Altan, Feray; Cetin, Gul; Bulbul, Aziz; Elmas, Muammer; Yazar, Enver
    The aim of this study was to determine the effect of tulathromycin on serum oxidative status and coagulation factors in rabbits. Tulathromycin was administered to eight rabbits, and blood samples were obtained 0, 1, 5, 10 and 15 days after treatment. Indicators of serum oxidative status (malondialdehyde, nitric oxide, superoxide dismutase, retinol and beta-carotene) and coagulation values (antithrombin III, fibrinogen) were measured after tulathromycin treatment. In addition, routine serum biochemical values (creatine kinase-MB, lactate dehydrogenase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, creatinine, blood urea nitrogen, cholesterol, triglyceride, high density lipoprotein, amylase, total protein, albumin, glucose and calcium), haemacell counts (white and red blood cells) and arterial blood gas parameters (packed cell volume, hemoglobin, pH, partial pressure of carbon dioxide, partial pressure of oxygen, actual bicarbonate, standard bicarbonate, total carbon dioxide, base excess in vivo, base excess in vitro, oxygen saturation, sodium and potassium) were also determined. Tulathromycin increased (P < 0.05) the levels of malondialdehyde, nitric oxide and superoxide dismutase activity, and decreased (P < 0.05) the level of antithrombin III. In conclusion, tulathromycin may cause oxidative damage and coagulation disorders during the treatment period.