Dexamethasone, which acts on nuclear receptors, is used together with P-gp and Cyp3a4 substrates at different doses in the treatment of diverse diseases. The aim of the study is to determine the effect of different doses of dexamethasone on the expressions and functions of P-gp and Cyp3a4 (mouse homologues of Cyp3a4 are Cyp3a11 and Cyp3a13). Animals (n=54) were divided into 9 equal groups. The control group was given only water. (The second group received fexofenadine, the third group received midazolam, the fourth group received low-dose dexamethasone, and the fifth group received high-dose dexamethasone. Low dose dexamethasone was administered to the sixth and seventh groups, and high dose dexamethasone was administered to the eighth and ninth groups.) 24 hours after these applications, fexofenadine was administered to the sixth and eighth groups, and midazolam was administered to the seventh and ninth groups. Synthesis of mdr1a, mdr1b, Cyp3a11 and Cyp3a13 in the small intestine and liver were determined using RT-qPCR. Plasma concentrations of fexofenadine and midazolam were determined using HPLC-UV. The effect of dexamethasone on Cyp3a11 expression was determined to be dose-related, while its effect on P-gp expression was not dose- related. Midazolam, a CYP3A substrate, did not cause P-gp induction in the small intestine, but did cause P-gp induction in the liver. Fexofenadine and midazolam reduced the effect of dexamethasone on Cyp3a11 expression in the small intestine. Dexamethasone dose-dependently decreased the plasma concentration of midazolam and increased that of its metabolite. Dexamethasone caused a dose-independent decrease in plasma concentrations of fexofenadine. The effect of dexamethasone on P-gp expression is not dose-dependent, but its effect on Cyp3a11 ve Cyp3a13 expression is dose-dependent. Fexofenadine and midazolam caused a reduction in the effect of dexamethasone on Cyp3a11 expression in the small intestine.

BACKGROUND:Neonatal diarrhoea is one of the most common diseases in lambs, causing economic losses and welfare issues. The endothelial glycocalyx (eGC) plays a crucial role in vascular integrity and inflammatory regulation. However, its involvement in neonatal lamb diarrhoea remains unclear. OBJECTIVES:This study aimed to evaluate eGC damage in neonatal lambs with diarrhoea by assessing biomarkers, including nitric oxide (NO), heparan sulphate (HS), angiopoietin-2 (Ang-2) and A disintegrin and metalloproteinase 15 (ADAM15). METHODS:A total of 68 neonatal lambs with diarrhoea (39 infected with Escherichia coli and 29 with Cryptosporidium parvum) and 20 healthy controls were included. Diarrhoea aetiology was confirmed via faecal antigen tests and microscopic examination. Blood samples were collected for hemogram and biomarker analysis using sheep-specific ELISA kits. RESULTS AND CONCLUSIONS:Lambs with diarrhoea showed significantly higher total leukocyte (white blood cell [WBC]), granulocyte (GRA) and monocyte (MON) counts (p < 0.01). Serum NO concentrations were significantly elevated in lambs with diarrhoea, whereas HS and Ang-2 concentrations were lower (p < 0.01). E. coli-infected lambs had significantly higher ADAM15 concentrations than those with Cryptosporidium infection (p < 0.001). These findings suggest that NO may have a protective and/or anti-inflammatory role in neonatal lamb diarrhoea, potentially maintaining eGC integrity despite the inflammatory process.

Tilmicosin shows different degrees of cardiotoxic effect in various animal species depending on the route of administration and dose. We aimed to determine the effects of amiodarone and amiodarone+dobutamine treatments on tilmicosincardiotoxicity and survival time. 18 healthy goats were divided into tilmicosin, tilmicosin+amiodarone and tilmicosin+amiodarone+dobutamine groups. After drug administrations, the survival times of the animals in all groups were recorded. In addition, blood was drawn from the animals just before they died. Haemogram, troponin I, CK-MB, and other biochemical parameters were measured in all blood samples. Prolonged survival was observed in the treatment groups compared to the tilmicosin group. In the treatment groups, decreases in haemogram parameters, albumin, and total protein levels caused by tilmicosin could not be prevented, while the increase in troponin I level was prevented. In conclusion, while cardiotoxicity due to high troponin from tilmicosin was prevented, the survival rate was not affected in both treatment groups, and the survival time was extended at differing rates. In case of accidental or deliberate overdose of tilmicosin in animals, in addition to the use of amiodarone+dobutamine, the survival time may be prolonged, and the success may increase if the necessary symptomatic treatments and equipment support are available.

This study aimed to determine the effects of Myrtus communis L. fruit extract on the diabetes-related glycemic and lipid profile, some serum biochemical parameters, and mRNA expression of some endogenous substances in type 2 diabetes. A total of 54 healthy male Swiss albino mice were divided into 5 groups. Except for the mice in the healthy control group, the mice in the other group were fed high-fat diets, and streptozotocin (50 mg/kg) was administered. No medication was administered to the animals in the diabetes control group. Metformin (200 mg/kg), Myrtus communis L. fruit extract (2 g/kg), and metformin +Myrtus communis L. fruit extract were administered orally to D+ metformin, D +Myrtus communis L. fruit extract, and D +Myrtus communis L. fruit extract+ metformin groups for 14 days, respectively. In serum samples, glucose, triglyceride, cholesterol, aspartate aminotransferase, alanine aminotransferase , and blood urea nitrogen were measured with an autoanalyzer and hemoglobin A1C (Hb1Ac) was measured with an Hb1Ac analyzer. Adiponectin, insulin, leptin, and adenosine monop hosph ate-a ctiva ted protein kinase levels were analyzed in an ELISA reader in serum samples. The mRNA expressions of glucose transporter-1 (GLUT-1), glucose transporter-4 (GLUT-4), peroxisome proliferator-activated receptor-alpha (PPAR-alpha), and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in the liver and striated muscles were determined with real-time polymerase chain reaction. Compared to the diabetic control group, Myrtus communis L. fruit extract significantly improved serum glucose, cholesterol, and triglyceride levels (p < .05) and significantly increased serum adiponectin, AMPK, and leptin levels (p < .05). The Myrtus communis L. fruit extract Myrtus communis significantly increased GLUT-1, PPAR-alpha, and PPAR-gamma mRNA expressions in striated muscle tissue (p < .05) but did not cause any changes in the liver. In conclusion, it may be stated that the Myrtus communis L. fruit extract had a significant positive impact on both glucose and lipid metabolism. Further studies are needed to elucidate the mechanisms of action of Myrtus communis L. fruit extract and its application in human diabetes treatment.

Çalışmanın amacı farelerde deneysel olarak oluşturulan tip 2 diyabetes mellitus (T2DM)’de sesamin, saponin, sesamin+saponin, tahin, çöven ektsraktı ve tahin+çöven ektsraktı uygulamalarının aspartat aminotransferaz (AST), alanin aminotransferaz (ALT), kan üre nitrojen (BUN) ve kreatinin düzeylerine etkisini belirlemektir. Araştırmada 48 adet Swiss albino erkek fare kullanıldı. Sekiz adet fare sağlıklı kontrol (SK) grubu için ayrıldıktan sonra diğer hayvanlarda yüksek yağlı besleme ve streptozotosin (STZ) uygulaması yapılarak T2DM oluşturuldu. T2DM oluşturulan 42 adet fare 7 gruba ayrılarak diyabet kontrol (DK), sesamin (D+SS), saponin (D+SP), sesamin+saponin (D+SS+SP), tahin (D+T), çöven ekstraktı (D+Ç) ve tahin+çöven ekstraktı (D+T+Ç) 2 hafta süresince uygulandı. Deney süresi sonunda anestezi altında kanları alınarak serum örnekleri toplanan fareler ötenazi edildi. Serum AST, ALT, BUN ve kreatinin düzeyleri otoanalizörde ölçüldü. AST düzeyi D+SP grubunda yüksek (p<0.05), D+SP, D+T ve DK gruplarında ise birbiri ile benzer bulundu (p>0.05). SK grubu AST düzeyi ise DK, D+SP, D+SS+SP ve D+T gruplarından düşük belirlendi (p<0.05). DK ile D+SP grupları ALT düzeyleri birbiri ile benzer bulunurken (p>0.05), diğer araştırma gruplarından farklı tespit edildi (p<0.05). SK ile DK grupları BUN değerleri birbirleri ile benzer bulunurken (p>0.05), iki grubun BUN değerlerinin diğer gruplardan farklı olduğu belirlendi (p<0.05). SK, DK, D+SP ve D+T gruplarının kreatinin düzeyleri birbirleri ile benzer (p>0.05) olarak tespit edilirken, diğer gruplardan farklı olduğu gözlendi (p<0.05). Sonuç olarak uygulanan maddelerin T2DM’de karaciğer ve böbrek fonksiyonu üzerine olumlu etkileri olabileceği ifade edilebilir.

The study was investigated the effect of different doses of levothyroxine on the mRNA expression, protein level and function of Pgp. Mice were divided into 6 groups as control, low dose levothyroxine, high dose levothyroxine, fexofenadine, low dose levothyroxine+fexofenadine and high dose levothyroxine+fexofenadine. Mice received levothyroxine at doses of 8 and 80 µg/kg daily for 21 days. Fexofenadine was administered at dose of 40 mg/kg at the 24 h following the last administration of levothyroxine. The mRNA levels and protein level of Pgp in liver and small intestine were determined by RT-PCR and western blot analysis, respectively. Plasma concentrations of fexofenadine were determined using HPLC. Levothyroxine at low and high doses caused an insignificant increase intestinal mRNA expression of mdr1a, while high dose levothyroxine+fexofenadine caused a significant increase. Levothyroxine caused a dose-dependent decrease in intestinal mRNA expression of mdr1b. In liver, levothyroxine caused a dose-dependent increase in the mRNA expression of mdr1a. Fexofenadine significantly reduced the effect of levothyroxine on mRNA expression of mdr1a in liver. Levothyroxine increased the protein level of Pgp in liver and decrease in intestines. Low dose levothyroxine significantly increased the plasma concentration of fexofenadine. The effects of levothyroxine on the mRNA expression of mdr1a and b in small intestine and liver and protein level of Pgp varied depending on the dose, tissue type, and fexofenadine administration.

This study aimed to determine the pharmacokinetics and pharmacokinetic interaction between oxfendazole (7.5 mg/kg) and oxyclozanide (15 mg/kg) tablet formulation administered either alone or co-administered to goats orally. The study was carried out to the cross-over design into three periods, with a washout period of 21 days among administrations, on six healthy Alpine goats 1 year of age. The plasma concentrations of oxfendazole, oxfendazole metabolites fenbendazole and fenbendazole sulfone, and oxyclozanide were determined using HPLC-UV, and data were analyzed by the non-compartmental method. The plasma concentrations of oxfendazole were similar in both oxfendazole and combined groups. When oxfendazole was administered alone or in com-bination with oxyclozanide, the compounds recovered in plasma were oxfendazole, fenbendazole sulfone, and fenbendazole. Oxyclozanide did not change the plasma disposition of oxfendazole. In the oxyclozanide group, t1/ 2 & lambda;z, Cmax, Tmax, and AUC0-& INFIN; were estimated at 15.3 h, 11.6 & mu;g/mL, 24 h, and 554 h x & mu;g/mL, respectively. In the oxyclozanide plus oxfendazole treatment group, AUC0-& INFIN; (1111 hx & mu;g/mL), and Cmax (23.9 & mu;g/mL) values were increased. In goats, the anthelmintic efficacy of oxfendazole and oxyclozanide should be determined by taking into account their pharmacokinetic data.

Racecadotril, used as an antidiarrheal drug in humans and some animals such as the dog, inhibits peripheral enkephalinase, which degrades enkephalins and enkephalinase inhibition induces a selective increase in chloride absorption from the intestines. The study material consisted of 46 calves with infectious diarrhea and 14 healthy calves in the age 2-20 days. The calves were divided into eight groups; healthy calves (HG), healthy calves administered racecadotril (HRG), calves with E.coli-associated diarrhea (ECG), calves with E.coli-associated diarrhea administered racecadotril (ECRG), calves with bovine Rotavirus/Coronavirus-associated diarrhea (VG), calves with bovine Rotavirus/Coronavirus-associated diarrhea administered racecadotril (VRG), calves with C. parvum-associated diarrhea (CG) and calves with C. parvum-associated diarrhea administered racecadotril (CRG). Calves in the racecadotril groups received oral racecadotril at a dose of 2.5 mg/kg twice a day for 3 days. A routine clinical examination of all calves was performed. Hemogram and blood gas measurements were made from the blood samples. Standard diarrhea treatment was applied to the HG, ECG, CG, and VG groups. Clinical score parameters such as appetite, feces quality, dehydration, standing and death and some blood gas and hemogram parameters were evaluated to determine the clinical efficacy of racecadotril. Clinical score parameters were determined observationally. Blood gas measurements were performed using a blood gas analyzer. The hemogram was performed using an automated hematologic analyzer. Statistically significant differences were determined in the blood pH, bicarbonate, base deficit, lactate, and total leukocyte count in calves with diarrhea compared to healthy calves. After the treatments, these parameters were found to be within normal limits. At the end of treatment, 42 of the 46 diarrheal calves recovered, while 4 died. We found that racecadotril was effective in improving both clinical recovery and feces consistency in neonatal calves with diarrhea caused by E. coli. As a result, it can be stated that racecadotril, which has an antisecretory effect, is beneficial in the treatment of bacterial diarrhea caused by such as E. coli.

This study aimed to determine the effect of administration of oral vitamins A and E at different doses on plasma and brain concentrations of ivermectin in mice. The study was carried out on 174 Swiss Albino male mice aged 8-10 weeks. After leaving six mice for method validation, the remaining mice were randomly divided into seven groups with equal numbers of animals. Mice received ivermectin (0.2 mg/kg, subcutaneous) alone and in combination with low (vitamin A: 4000 IU/kg; vitamin E: 35 mg/kg) and high (vitamin A: 30 000 IU/kg; vitamin E: 500 mg/kg) oral doses of vitamins A and E. The plasma and brain concentrations of ivermectin were measured using high-performance liquid chromatography-fluorescence detector. We deter-mined that high doses of vitamins A and E and their combinations increased the passing ratio of ivermectin into the brain significantly. The high-dose vitamin E and the combination of high-concentration vitamins E and A significantly increased the plasma concentration of ivermectin (P < 0.05). The high-dose vitamins E and A and their high-dose combination increased the brain concentration of ivermectin by 3, 2, and 2.7 times, respectively. This research is the first in vivo study to determine the interaction between P-gp substrates and vitamins E and A.

Türkiye’de son yıllarda büyükbaş hayvancılık sektöründe önemli değişimler yaşanmıştır. Bu süreçte birim hayvan başına düşen verim düzeyleri artmış olmakla birlikte; nüfus artışıyla birlikte oluşan damızlık ve kasaplık hayvan talebi iç piyasadan yeterince karşılanamamıştır. Ülkemizde artan hayvansal ürün ihtiyacının karşılanabilmesi yanında ithalatın azaltılabilmesi ve sürdürülebilir bir hayvancılık için hayvansal üretimdeki kayıpların en aza indirilmesi gerekmektedir. Bu bağlamda sığırcılık işletmelerinde en önemliüretim zararlarından birisi “buzağı kayıpları” olarak karşımıza çıkmaktadır. İneklerde Gebeliğin Elde Edilmesi ve Döl Verimi ile İlgili Kayıplar Hüseyin ERDEM İneklerde Gebelik Muayene Zamanlarının Planlanması Hüseyin ERDEM Fatma SATILMIŞ Kuru Dönemde Bakım ve Beslemenin Buzağı Sağlığı Üzerine Etkileri Behiç COŞKUN Mikotoksinlerin Buzağı Kayıplarına Etkisi Halis OĞUZ İneklerin Gebeliğinde Önemli Bir Sorun: Yavru Atıkları (Abortus) Fatma SATILMIŞ Furkan ÇİFTÇİ Ö. Faruk YEŞİLKAYA Hüseyin ERDEM Doğuma Yardımda Buzağı Kayıplar D. Ali DİNÇ S. Ülküm ÇİZMECİ Yeni Doğan Buzağılarda Kolostrum Yönetiminin Önemi Mahmut OK Prematüre (Günsüz) Doğan Buzağıların Bakımı Mahmut OK Sütten Kesim Döneminde Buzağıların Beslenmesi ve Buzağı Kayıplarının Önlenmesi Nurettin GÜLŞEN Buzağıların Süt Emme Dönemindeki Beslenmesi Fatma İNAL İbrar AHMED Buzağıları Hastalıklardan Koruma Yöntemleri Mahmut OK Buzağılarda Bakteriyel Hastalıklar Hüseyin HADİMLİ Buzağı Kayıplarına Neden Olan Viral Hastalıklar Oya BULUT Buzağı Kayıplarında Şap Hastalığının Rolü Murat ŞEVİK Mehmet Kürşat IŞIK Yeni Doğan Buzağılarda İshale Neden Olan Başlıca Paraziter Hastalık: Cryptosporidiosis Ferda SEVİNÇ Onur CEYLAN Buzağılarda Myiasis Uğur USLU Buzağılarda Coccidiosis Onur CEYLAN Ferda SEVİNÇ Buzağılarda Görülen Önemli Ektoparazitler Uğur USLU Buzağılarda Doğum Sonrası Dönemde Görülen Eklem Hastalıkları, Tedavi Seçenekleri ve Korunma Yolları Mustafa ARICAN Nuriza ZAMİRBEKOVA Buzağılarda Doğum Sırasında ve Sonradan Olan Kırık Olgularında Tedavi Seçenekleri Mustafa ARICAN Fehmiye GÜMÜŞ Birol ÖZDİL Yeni Doğan Buzağılarda Göbek Bölgesi Problemleri Fahrettin ALKAN Kurtuluş PARLAK Mustafa KUL Yeni Doğan Buzağılarda Acil Müdahaleler Mehmet MADEN Süt İnekleri ve Buzağılar İçin Aşılama Programları Hüseyin HADİMLİ Sığırlarda Akılcı İlaç Kullanımı Bünyamin TRAŞ Kamil ÜNEY Buzağı Barındırma Sistemleri Mustafa ÇAM Şeref İNAL Sığır İşletmelerinde Biyogüvenlik Erdem DANYER Sabri HACIOĞLU Cevdet YARALI Buzağı Kayıplarında İşletme Hatalarının Rolü Emine ÇİFTCİ Buzağı Yetiştirmede Refah Uygulamaları Kürşat IŞIK Buzağı Kayıpları ve Buzağı Hastalıklarının Ekonomik Değerlendirmesi Aytekin GÜNLÜ Sütçü Sığır İşletmelerinde Buzağı Kayıplarının Analizi: Nedenleri, Risk Faktörleri ve Hedefleri Mehmet MADEN Tarım ve Orman Bakanlığı Veteriner Kontrol Enstitüleri Erdem DANYER Sabri HACIOĞLU Cevdet YARALI Buzağı Yetiştirmede Kontrol ve Değerlendirme Listesi Şeref İNAL Mustafa ÇAM

Türkiye Ekonomisinde Koyun-Keçi Yetiştiriciliğinin Yeri ve Önemi Aytekin GÜNLÜ, Burak MAT KOP Bölgesine Uygun Koyun-Keçi Irklarının Özellikleri ve Damızlık Seçimi Kriterleri Mustafa GARİP, Emre ARSLAN Küçükbaş Hayvancılıkta Yetiştirme Sistemleri: Çevre Şartları ve Barınaklar Ümit YORGANCILAR Koyun ve Keçilerin Beslenmesinde Çayır ve Meralar Fatma İNAL, İbrar AHMED Koyun-Keçi Sütü Gürkan UÇAR, Yusuf BİÇER Koyun-Keçi Eti Tahir YILMAZ, Abderraouf BOUGHEZELA, Ahmet GÜNER Yapağı-Tiftik Esad Sami POLAT Küçükbaş Hayvancılıkta Sürü Yönetimi Orhan ERMETİN Koyun ve Keçi Refahı Kürşat IŞIK, Onur ERZURUM Koyun-Keçilerde Bakım ve Beslenmenin Önemi Mustafa Selçuk ALATAŞ Koyun-Keçi İşletmelerinde Kuzu-Oğlak Büyütme Döneminde Olması Gereken Yapısal ve Teknik Uygulamalar Cafer TEPELİ Mikotoksinlerin Kuzu-Oğlak Kayıplarına Etkisi Halis OĞUZ Yıllık Kuzu/Oğlak Verimini Artırma Yolları Mehmet Emin TEKİN Kuzu/Oğlak Bakım-Besleme ve Yönetimi Orhan ERMETİN Kuzu ve Oğlakların Beslenmesinde Başlangıç Yemlerinin Önemi Nurettin GÜLŞEN Kuzu-Oğlak Kayıplarında İşletme Hatalarının Rolü Emine ÇİFTCİ, Kübra BİÇER Uygulanabilen Biyoteknolojik Yöntemler Tevfik TEKELİ, Hasan ALKAN, Kübra KARAKAŞ ALKAN Koyun ve Keçilerde Üremenin Denetlenmesi Mehmet GÜLER, Fatma SATILMIŞ Koyun-Keçilerde Gebeliğin Belirlenmesi Hüseyin ERDEM Koyun-Keçilerde Doğum ve Doğuma Yardım Girişimleri Hüseyin ERDEM, Ö. Faruk YEŞİLKAYA, M. Furkan ÇİFTÇİ Koyun-Keçilerde Sağım Hüseyin ERDEM, Kübra KARAKAŞ ALKAN Koyun ve Keçilerde Önemli Hastalıklar Mutlu SEVİNÇ, Merve İDER Koyun ve Keçilerde Metabolik Profil Testinin Değerlendirilmesi Mutlu SEVİNÇ Koyun ve Keçilerin Metabolik ve Beslenme Hastalıkları Mutlu SEVİNÇ Koyun ve Keçilerin Ayak Hastalıkları Fahrettin ALKAN, Mustafa KUL, Fatma BORAN ÇAYIRLI Koyun ve Keçilerin Ayak Hastalıklarında Tanı ve Tedavi Yöntemleri ile Koruyucu Önlemler Fahrettin ALKAN, Kurtuluş PARLAK, Kadir SULU Koyun-Keçilerde Meme Sağlığı ve Mastitis Fatma SATILMIŞ, Hasan ALKAN Koyun ve Keçilerde Ani Ölümle Seyreden Hastalıklar Mahmut OK, Merve İDER Koyun ve Keçilerde Hastalıklardan Korunmada Koruyucu Hekimlik ve Aşılama Stratejileri Mahmut OK, İbrahim Kubilay YILDIZ Koyun ve Keçilerde Görülen Önemli Dış Parazitler Uğur USLU Kırım Kongo Kanamalı Ateşi Uğur USLU Koyun-Keçilerde Önemli İç Paraziter Hastalıklar ve Mücadele Yöntemleri Nermin IŞIK USLU Küçükbaş Hayvanlarda Akılcı İlaç Kullanımı Bünyamin TRAŞ Koyun-Keçilerde Yavru Atıklarına Neden Olan Bakteriyel Hastalıklar Hüseyin HADİMLİ, Esra ASLAN, Adam Bashir Tawor ELDOW Küçükbaş Hayvanlarda Yavru Atıklarına Sebep Olan Viral Hastalıklar Oya BULUT Koyun-Keçilerde Yavru Atıklarına Neden Olan Paraziter Hastalıklar Özlem DERİNBAY EKİCİ Koyun-Keçi İşletmelerinde Biyogüvenlik Onur ERZURUM, M. Kürşat IŞIK, Emine ÇİFTCİ Kuzu-Oğlak Ölümlerinde Numune Alma ve Gönderme Kriterleri Hekim Yalçın FAKI, Hekim İsa KAPLAN Koyunculuk İşletmelerinde Değerlendirme ve Kontrol Listesi Şeref İNAL, Mustafa ÇAM

This study was aimed to determine the pharmacokinetics of antisecretory-acting racecadotril, used in the treatment of diarrhea in humans and dogs, following oral administration in both neonatal calves with healthy and neonatal calves with infectious diarrhea. The study was carried out on a total of 24 Holstein calves (2-20 days), of which 6 were healthy and 18 were infectious diarrhea. Calves with infectious diarrhea were divided into 3 groups according to the infectious agent (Escherichia coli, Cryptosporidium parvum, and rotavirus/coronavirus). Racecadotril was administered orally at 2.5 mg/kg dose to calves. The plasma concentrations of racecadotril and its main active metabolite (thiorphan) were determined using HPLC-UV. The pharmacokinetic parameters were analyzed using the non-compartmental method. In healthy calves, the t1/2ʎz , Cmax , Tmax, and AUC0-12 of racecadotril were determined 4.70 h, 377 ng/ml, 0.75 h, and 1674 h × ng/ml, respectively. In the plasma of calves with infectious diarrhea, racecadotril and thiorphan were only detected at the sampling time from 0.25 to 1.5 h. As in calves with infectious diarrhea, thiorphan in plasma was only detected in healthy calves from 0.25 to 1.5 h. Racecadotril showed a large distribution volume, rapid elimination, and low metabolism to thiorphan in healthy calves.

The combination of oxfendazole and oxyclozanide is used to provide activity against fluke and gastrointestinal nematodes. This study aimed to determine both the pharmacokinetics of oxfendazole (7.5 mg/kg) and oxyclozanide (15 mg/kg) tablet formulation administered orally to sheep and whether there is a pharmacokinetic interaction between these two drugs. The study was conducted in a three-period, crossover pharmacokinetic design and on six healthy Awassi sheep 1-3 years of age. The plasma concentrations of oxfendazole and its metabolites (fenbendazole and fenbendazole sulphone) and oxyclozanide were determined by high-performance liquid chromatography using an ultraviolet detector. Compounds recovered in plasma when oxfendazole was administered alone or combined with oxyclozanide were oxfendazole, fenbendazole sulphone, and fenbendazole, respectively. When oxfendazole was administered alone and co-administered with oxyclozanide, the AUCFBZ /AUCOFZ was 0.26 and 0.23, respectively, and the AUCFBZSO2 /AUCOFZ was 0.35 and 0.32, respectively. The volume of distribution (Vz/F) of oxfendazole was large in both groups. Oxyclozanide did not change the plasma disposition of oxfendazole. When the oxyclozanide tablet formulation was administered alone, the elimination half-life (21.35 h) and the Vz/F (940.17 ml/kg) were long and large, respectively. The area under the curve (AUC) and the maximum plasma concentration of oxyclozanide were significantly larger and higher, respectively, in the oxyclozanide plus oxfendazole group (1146.61 h × μg/ml and 29.80 μg/ml) compared with the oxyclozanide group (491.44 h × μg/ml and 14.24 μg/ml) while a significant decrease in apparent Vz/F (940.17 vs 379.14 ml/kg) and total clearance (30.52 vs 13.08 ml/h/kg) was detected. In conclusion, co-administration with oxfendazole causing an increase in the plasma profile of oxyclozanide may increase the antiparasitic activity of oxyclozanide.

This study aimed to determine the effects of dexamethasone and minocycline alone and combined treatment with N-acetylcysteine (NAC) and vitamin E on serum coenzyme Q10 (CoQ10) and matrix metalloproteinase-9 (MMP-9) levels in rats administered aflatoxin B1 (AFB1). The study was carried out on 66 male Wistar rats. Following the intraperitoneal (IP) administration of AFB1 at dose of 2 mg/kg, minocycline (45 and 90 mg/kg, IP) and dexamethasone (5 and 20 mg/kg, IP) were administered alone and combined with NAC (200 mg/kg, IP) and vitamin E (600 mg/kg, IP). CoQ10 and MMP-9 levels were analyzed using the HPLC-UV method and a commercial kit by ELISA, respectively. AFB1 increased MMP-9 level and decreased CoQ10 level compared to the control group. After dexamethasone and minocycline administration, there is no increase in CoQ10 level, which is caused by AFB1. However, dexamethasone and minocycline combined with NAC+vitamin E caused significant increases in CoQ10 levels. Dexamethasone and minocycline alone and combined with NAC+vitamin E decreased MMP-9 levels compared to the single AFB1 treated group. The use of MMPs inhibitors and oxidative stress-reducing agents is anticipated to be beneficial in the poisoning with AFB1.

This study aimed to assess the clinical efficacy of pentoxifylline (PTX) and L-glutamine (L-Gln) treatment on ischemia and reperfusion (I/R) injury in the abomasal tissue, acute phase response (APR), oxidative stress (OS), cytokine response, hemostatic, and coagulation disorders in the 96-h period before and after surgery in displaced abomasum (DA) cases. The study sample consisted of 48 dairy cows with DA that were categorized into four groups as group S (Sham group) (9 Left displaced abomasum (LDA)+3 Right displaced abomasum (RDA), group P (PTX) (10 LDA+2 RDA), group G (L-Gln) (10 LDA+2 RDA), and group P+G (PTX+L-Gln) (10 LDA+2 RDA). Acute-phase protein (Haptoglobin), oxidative stress indicators (malondialdehyde, nitric oxide, and glutathione), cytokines (tumor necrosis factor (TNF)-α and interleukin-1β (IL-1β), coagulation factors (D-Dimer, Antithrombin (ATIII), Thrombin-antithrombin complex, Plasminogen activator inhibitor-1), and enzyme activities (lactate dehydrogenase, gamma- -glutamyl transferase, sorbitol dehydrogenase, glutamate dehydrogenase, adenosine deaminase, myeloperoxidase, and creatine phosphokinase) in blood serum samples and coagulometric analyses of blood plasma were performed in samples taken before the operation and at 30 and 60 min and 2, 5, 10, 24, 48, 72, and 96 h after the operation. In DA cases, while post-operative treatment procedures with PTX and L-Gln were effective in decreasing APR and OS, these were ineffective in prohibiting the inflammatory response coordinated by cytokines. For the treatment and prevention of I/R injury in the DA cases, PTX and L-Gln procedures hold promise with their effects on APR, OS, and hemostatic dysfunction. Additional treatment procedures are required for the suppression of inflammatory response, and the effectiveness of preconditioning treatment may be evaluated.

This study was conducted to investigate the effects of matrix metalloproteinase (MMP) inhibitors dexamethasone and minocycline administrations -both single and in combination with N-acetylcysteine (NAC) and vitamin E-on the tissue distribution and lethal dose (LD)(50) of aflatoxin (AF)B-1 in rats. We performed this study on male Wistar rats (8-10 weeks) in two phases. In the first phase, rats were administered dexamethasone (5 and 20 mg/ kg) and minocycline (45 and 90 mg/kg), both as single treatments and in combination with NAC (200 mg/kg) and vitamin E (600 mg/kg); these treatments followed AFB(1) administration (2 mg/kg). In the second phase, the therapeutic effect value (TEV) was calculated to determine the treatment effect on the LD50 level of AFB(1.) The tissue affinity of AFB(1) from high to low was liver, kidney, intestine, brain, heart, spleen, lung, testis, and vitreous humor, respectively. Dexamethasone at the 20 mg/kg dose significantly reduced AFB(1) concentrations in the plasma and the other tissues, except for the vitreous humor. The effects of minocycline on the plasma and tissue concentrations of AFB(1) varied by dose and tissue. The combinations of dexamethasone or minocycline with NAC and vitamin E increased the AFB(1) concentrations in the plasma and all tissues, except for vitreous humor and liver. In male rats, the LD50 value of AFB(1) was 11.86 mg/kg. The TEV of dexamethasone (20 mg/kg) was calculated to be 1.5. Dexamethasone can be administered in repeated doses at >= 20 mg/kg to increase survival in AFB(1) poisoning.

Canlı vücudunda tamamı sentezlenemeyen vitaminler, fizyolojik fonksiyonlar için gerekli olup kendilerine özgü spesifik görevleri olan maddelerdir. İlaç-ilaç ve ilaç-gıda etkileşimleri, ilaçların istenmeyen etkilerinin ortaya çıkmasında büyük rol oynar. Farmakokinetik temelli ilaç etkileşimleri daha çok enzim ve taşıyıcı transmembran proteinler düzeyinde gözlenir. Metabolik reaksiyonların çoğu sitokrom P450 ailesi tarafından gerçekleştirilir. Enzim aktivitesinin, inhibisyonu veya indüksiyonu substrat ilacın konsantrasyonunu değiştirir. ATP-bağlayıcı kaset taşıyıcılarından, Pglikoprotein ve meme kanser direnç proteini toksik maddelerin ve ksenobiyotiklerin hücrelerden dışarı atılmasında ve ilaç-ilaç, ilaç-gıda etkileşimlerinde rol oynarlar. Çoğu ilaç etkileşimlerinde, sitokrom P450 ve P-glikoprotein birlikte rol oynar. Hem farmakokinetik ve hem de farmakodinamik etkileşimler, ilaçların farmakolojik etkinliğinde artış ve azalışa neden olabilir. Etkide artış ölüme yol açabilecek düzeyde bir etkileşim oluşturabilirken, etkide azalış ise tedavide başarısızlığa neden olabilir. İlaçlar arasındaki etkileşimin klinik önem arz edip etmeyeceği, etkileşime giren ilaçların terapötik indeks ve vücuttaki farmakokinetik davranış özelliklerinin bilinmesiyle ön görülebilir. Vitaminler, hem beşeri hem de veteriner hekimlikte en fazla suistimal edilen bileşikler arasındadır. İnsan ve hayvanların, besinlerle aldıkları vitaminlere ilave olarak kullanılan vitaminler sağlık açısından risk oluşturmakta ve ilaç etkileşimlerinde çoğu kez vitaminlerin etkisi göz ardı edilmektedir. Vitaminlerle ilaçlar arasındaki etkileşimleri belirlemeye yönelik daha çok deneysel ve klinik çalışmalara ihtiyaç vardır. Bu derlemede, yoğun kullanılan vitaminlerin ilaç etkileşimlerindeki önemi irdelenecektir.

P-glycoprotein (P-gp), a transporter membrane protein, plays an important role in various physiological and physiopathological conditions, drug-drug and drug-food interactions, and multi-drug resistance. Nowadays, P-gp modulators are used consciously to treat some specific diseases, such as cancer and poisoning. Levofloxacin (LVX), a P-gp substrate, may cause the stimulation of the central nervous system. The aim of this study was to determine the effects of fexofenadine (FEX) and dexamethasone (DEX) with P-gp modulators on the distribution of LVX in rat brain, testicle, and plasma. In the in vivo section of the study, LVX concentrations in tissue and plasma samples were detected by high-performance liquid chromatography. In addition, in silico molecular docking studies were conducted to elucidate interactions between P-gp and drugs. The administration of DEX at a low dose and minute 30 reduced the LVX passage to the brain, while the administration of DEX at a high dose and hour 2 increased the LVX passage to the brain, testicle tissue, and plasma. MM-GBSA.G values of FEX, DEX, and LVX were calculated to be 80.95, 57.74, and 52.12 kcal/mol, respectively. The results of this study reported that DEX, known as a P-gp inductor, may show inhibitory activity based on dose, tissue, and time of application.

This study aimed to determine lipid peroxide (LPO), antioxidant capacity (AOC), and acute-phase protein changes before and after different nebulization treatments in premature calves with respiratory distress syndrome (RDS). Thirty-six premature calves were divided into equal number of 6 groups. Group 1 was labelled as negative control and received standard treatment. Group 2 was labelled as positive control; Groups 3, 4, 5, and 6 were labelled as trial groups. These groups received nebulizer treatment. Nebulizer drug combinations were as follows: Group 2 (fluticasone), Group 3 (formoterol + fluticasone), Group 4 (ipratropium bromide + fluticasone), Group 5 (fluticasone + furosemide) and Group 6 (formoterol + ipratropium bromide + furosemide + fluticasone). Venous blood was taken from all calves before (0 hour) and after treatment (24th, 48th, 72nd hour). It was concluded that total LPO levels gradually decreased while AOC levels increased during treatment but there was no difference in the serum amyloid A (SAA) and fibrinogen levels within groups. In conclusion, supportive and nebulizer treatments to improve function of lungs were demonstrated to alleviate oxidative stress. However, in order to reveal the effects of local nebulizer applications on oxidative stress, further studies are required to investigate oxidation parameters in the bronchoalveolar fluid.

The purpose of this study was to assess the clinical effect of nebulized formoterol (FM), ipratropium bromide (IB) and furosemide (FS) combined with fluticasone propionate (FP) on l ung function in premature calves with Respiratory Distress Syndrome (RDS). Thirty-six premature calves with RDS were randomly assigned to six different treatment groups (D1 to D6). All groups received the standard treatment, including oxygen and support treatment. Calves in D1 received only the standard treatment. The following combinations of nebulized drugs were used for the other groups: D2: FP, D3: FP+FM; D4: FP+IB; D5: FP+FS and D6: FP+IB+FM+FS. The treatment period (72 h) involved the application of FM (15 μg totally/12 h), IB (2 μg/kg/12 h), FS (1 mg/kg/12 h) and FP (15 μg/kg/12 h) for five minutes. A significant increase over time in blood pH, partial pressure of oxygen (PaO2), oxygen saturation (SatO2) and a decrease in partial pressure of carbon dioxide (PaCO2) and lactate were detected in all groups that received nebulized treatment; while in the D1, a significant change was observed only for PaCO2. Calves in D6 had the highest PaO2 and lowest PaCO2 values amongst all groups at the end of treatment. No statistical difference was observed between the Nebulization Groups (NG). Nebulized FM, IB and FS with FP combination in premature calves with RDS, in addition to the standard treatment showed a significant curative effect on lung function.