Research of differentiations in physiological parameters of rats which were housed in different facilities under different care conditions

Laboratuvar hayvanlarıyla yapılan deneysel çalışmalarda, güvenilir sonuçların elde edilmesi ve çalışmaların tekrarlanabilirliği temel öneme sahiptir. Konvansiyonel yetiştirilen laboratuvar hayvanlarının kullanıldığı bilimsel araştırmalarda, çalışmaya alınan laboratuvar hayvanlarının fizyolojik özelliklerinin standart olduğu varsayılır. Fakat laboratuvar hayvanlarının bakım şartları standart değilse bu varsayım çoğu zaman doğru değildir. Gelişmiş ülkelerde, ülke genelinde yapılan çalışmalarda standardizasyonu sağlamak için üretim yapan firmalar ile bu hayvanların kullanıldığı araştırma merkezleri ayrı tutulmuştur. Fakat yurdumuzda hemen her tıp fakültesinin laboratuvar hayvanı üretim merkezi bulunduğu için farklı üniversitelerde yetiştirilen laboratuvar hayvanlarının yetiştirilme şartları birbirlerinden farklı olabilmektedir. Bu nedenle çalışmamızda, ülkemizde üniversite rektörlüklerine bağlı farklı laboratuvar hayvanları üretim merkezlerindeki konvansiyonel sıçan yetiştirme koşullarını, standart kabul edilen koşullarla karşılaştırarakæ ülkemizde yapılan çalışmalar yurt içinde ve yurt dışında tekrarlandığında elde edilecek sonuçların birbirine yakın olması sağlanacaktır. Böylece ülkemizde yapılan çalışmaların hem standardizasyonu hem de güvenilirliği arttırılacaktır. Bu projede etik kurul onayı alındıktan sonra Türkiye'de yedi laboratuvar hayvanı yetiştirme merkezi çalışmaya dahil edildi. Her bir merkezde hayvan yetiştirme odalarında yapılan ölçümlerde ısının bir merkezde yüksek, nemin bütün merkezlerde düşük, ışık ve gürültü şiddetlerinin bütün merkezlerde standart seviyede olduğu belirlendi. Merkezde yetiştirilen yetişkin Wistar ve/veya Sprague Dawley suşları erkek ve dişilerinde yapılan kan şekeri ölçümleri normal parametreler içinde olmasına rağmen bir merkezde diğerlerine göre yüksek bulundu. Alınan sıçan kanlarının tüm hemogram ölçümlerinde bir merkezde alyuvar sayısıæ bir merkezde hemoglobin sayıları standart değerlere göre yüksek bulunmuştur. Parazitolojik inceleme için alınan dışkı örneklerinde iki merkezde Giardia sp. bir merkezde E. coli saptanmıştır. Belirlenen bu farkların ana nedeni Türkiye'de laboratuvar hayvanı yetiştirilen hiçbir merkez binası inşaatının merkeze özgü yapılmamış olmasıdır. Bu nedenle standart yetiştirme koşulları bilinse bile teknik sorunlar bu koşulların uygulanmasını zorlaştırmaktadır In scientific studies in which laboratory animals were used, the repeatability of experiments and obtaining reliable results have basic importance. It is assumed that physiological characteristics of the animals included in the experiment are the same, but if housing conditions are not the same this assumption is mostly wrong. In developed countries, to obtain standardization in experimental studies, the research centers that animals are used and the firms that breed laboratory animals were separated. But in Turkey as nearly every medical faculty has laboratory animal breeding facility, housing conditions of laboratory animals might be different from each other. Therefore, to make research results closer to each other even if the study repeated in other countries and to increase the reliability and standardization of the researches done in Turkey, we compared conventional rat breeding conditions in different laboratory animal breeding facilities of the different medical faculties with the conditions that accepted as standards. After approved by the ethical committee, 7 laboratory animal breeding facility were included in this study. In animal breeding rooms of each facility it was measured that room temperature of one facility was higher than the others, humidity was low in each facility, noise and light levels were standard. Although, blood glucose measurements of adult male and female Wistar and/or Sprague Dawley stocks bred in the facility were observed within the standard parameters, in one facility it was observed higher than others. In one facility erythrocyte counts and in other facility hemoglobin counts were observed higher than the standard values In, 2 facilities Giardia sp., and in 1 facility E. coli were determined by the parasitological examination of feces samples. The main reason of these differences was that none of the laboratory animal facility building was built specially for the facility. Therefore, even if the standard housing conditions are known technical problems make difficult carrying it out

Effect of Tacrolimus in Triple Negative Breast Cancer Animal Model

Aim: Triple negative breast cancer has poor prognosis requiring new combination treatments strategies. Structurally resembling the best known mTOR inhibitor of rapamycin and a calcineurin inhibitor, tacrolimus modulates mTOR in the absence of rapamycin with antiproliferative efficacy shown for cancer types like glioblastoma multiforme, hepatocellular carcinoma, and lymphoma, the aim of this study is to assess the efficacy of tacrolimus on tumor cells from an in vitro 4T1 cell line representing triple-negative breast cancer and in a cancer model in experimental animals. Method: 4T1 triple-negative breast cancer cell line was incubated with tacrolimus (1, 10, 20, 30, 40, 50, 100 µm) for 24, 48 and 72 hours. Cell viability percentages were assessed with WST-1 analysis. 14 athymic nude mice with mean weight 25 g aged 5-7 weeks were injected with 4T1 cells subcutaneously. After 150 mm3 tumor development, animals were randomized into a control group administered physiologic serum and an experimental group administered 10 mg/kg tacrolimus, on the 1st and 8th days via the intraperitoneal route. On the 14thday, animals were sacrificed and changes in tumor tissue were examined histopathologically and for apoptosis with flow cytometry with annexin-V and propidium iodide in fresh tissue suspension. Results: The LD50 dose of tacrolimus was identified as 30 µM. In the triple-negative breast cancer model in experimental animals, the targeted tumor size was reached in 8-12 days. Side effects were not observed from the two doses of tacrolimus administered at a one-week interval. After sacrifice on the 14th day, histopathologic assessment of tumor tissues observed prominent necrosis, necrobiosis and apoptosis in the tumor group compared to the control group. Annexin-V+PI flow cytometry investigation found the early apoptotic effect of tacrolimus was higher compared to late apoptosis and necrosis. Conclusion: Tacrolimus was found to be effective both in vitro and in vivo on triple-negative breast cancer triggering necrosis in addition to apoptosis. Tacrolimus is promising as a treatment choice for the clinical problem of triple-negative breast cancer.</p

Anti-inflammatory activity of Anthemis aciphylla var. aciphylla Boiss.

WOS: 000298197800014Ethanolic (EEAA) and sesquiterpene lactone (SEAA) extracts of the aerial parts of Anthemis aciphylla var. aciphylla Boiss. (Asteraceae) were evaluated for anti-inflammatory activity on carrageenin-induced paw edema (acute model) and cotton pellet-induced granuloma (chronic model) in rats. In carrageenin-induced paw edema, EEAA and SEAA at intraperitoneal doses of 50, 100, and 200 mg/kg dose-dependently inhibited the paw edema. In cotton pellet-induced granuloma, the oral administration of EEAA and SEAA at 50, 100, and 200 mg/kg dosages was also found to significantly inhibit granuloma tissue formation.Ege University, Izmir, TurkeyEge University [2008/ECZ/001]This research was supported by Ege University's Research Fund (No. 2008/ECZ/001), Izmir, Turkey

Ghrelin may attenuate proinflammatory cytokine-mediated neuropathic pain

Nerve damage that affects peripheral or central nerve systems leads to abnormal pain states referred to as neuropathic pain. The precise mechanisms in neuropathic pain are very complex, since they are thought to originate through multiple pathophysiological processes. There is quite evidence implicating the proinflammatory cytokines in the induction and facilitation of neuropathic pain. This pain syndrome is usually poorly controlled by available medications. Ghrelin, a peptide hormone predominantly secreted from the stomach, is an endogenous ligand to the growth hormone secretagogue receptor. Previous studies showed that ghrelin has potent anti-inflammatory effect; inhibiting proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) interleukin-1 beta (IL-1 beta) and interteukin-6 (IL-6). Furthermore, there are recent studies which prove the interaction between ghrelin and the systems that play role in pain modulation. Therefore, we hypothesize that ghrelin might ameliorate neuropathic pain by diminishing the proinflammatory cytokines and also regulating pain system. (c) 2007 Published by Elsevier Ltd