shigatox.net/ecmlst/cgi-bin/strainquery and the sequence of ECA-B was provided by Dr. Kenneth kinase inhibitor MEK162 Simpson. Allele, st7 and clonal group were determined using the EcMLST web-based software (http://www.shigatox.net/ecmlst/cgi-bin/mlbquery). Bovine Primary Endometrial Cell Isolation and Culture Primary endometrial epithelial and stromal cells were isolated and cultured as described previously [18]. Briefly, bovine uteri were collected from post-pubertal non-pregnant animals with no evidence of genital disease or microbial infection at a local abattoir and kept on ice until further processing in the laboratory. The stage of the reproductive cycle was determined by observation of ovarian morphology and genital tracts with an ovarian Stage II corpus luteum were selected for endometrial culture [40].

The endometrium from the horn ipsilateral to the corpus luteum was cut into strips and placed into PBS (Sigma, Poole, UK) supplemen
Imatinib is a selective inhibitor of tyrosine kinases, comprising Bcr-Abl fusion protein in chronic myeloid leukaemia (CML) and the c-kit proto-oncogene in gastrointestinal stromal tumour (GIST). It has demonstrated an impressive clinical efficacy in both malignancies. Inducing durable responses and achieving prolonged survival, imatinib has become the standard of care for the treatment of these diseases. However, imatinib treatment is not devoid of toxicity and resistance occurs in some instances. Besides cellular mechanisms of resistance (gene amplification and mutation), variability in binding to ��1-acid glycoprotein (AGP) can modulate its activity [1, 2�C5].

Indeed, only the free drug is likely to equilibrate with the intracellular milieu to exert its pharmacological action. Moreover, a small change in the extent of protein binding may result in a significant impact on imatinib free fraction and on its concentration�Ceffect relationships [5, 6]. Although there are many circulating proteins in plasma capable of binding drugs, the majority of drugs bind to human serum albumin (HSA) and AGP [7]. HSA is the most abundant protein in plasma, whereas the normal AGP concentrations are much lower, resulting in a lower capacity to bind drugs and a more rapid saturation of the protein [8]. Both are capable of binding a broad variety of drugs with sufficient affinity to impact on the pharmacologically active free fraction.

HSA is the primary binding protein for acidic drugs, while binding to AGP is more commonly observed with basic lipophilic agents. Changes in the concentration, conformation, and/or other physicochemical characteristics of these proteins may result in significant changes in the Cilengitide drug free fraction [9]. Alterations in albumin concentrations in plasma occur as a result of altered synthesis, loss, or a shift of fluids between body compartments.