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Satué K., Montesinos P., Muños A. (2017): Activation of the renin-angiotensin-aldosterone system in mares around ovulation. Czech J. Anim. Sci., 62,[259][260][261][262][263][264][265][266][267] Many physiological events occurring during the estrous cycle, including folliculogenesis, oocyte maturation, ovulation, follicular atresia, corpus luteum development, luteolysis, steroidogenesis, and angiogenesis are associated with an increased expression of the renin-angiotensin-aldosterone system (RAAS) in uterus and ovarian follicles. This enhanced expression leads to a rise in plasma concentrations of these hormones in women and laboratory animals, and the same might happen in the mare. This study aims to assess if an activation of the RAAS occurs in mares around ovulation and if this activation is related to the diameter of the predominant follicle (DPF), packed cell volume (PCV), and electrolyte concentrations. Twenty-five healthy Spanish Purebred mares were sampled during the five days before ovulation, the day of ovulation, and the first five days after ovulation. Renin (REN) concentrations increased progressively during the five days before ovulation, achieving the highest values on the day of ovulation. Angiotensin (ANG) concentrations showed a sharp decrease after ovulation, with the lowest values the fifth day after it. Aldosterone (ALD) concentrations increased progressively, from the fifth day before ovulation until the fifth day after ovulation. The highest PCV values were found on the day of ovulation. There were no relevant correlations between the RAAS components and electrolytes concentrations. Before ovulation, there was a positive relationship between REN and ALD (r = 0.760) and after ovulation, a negative correlation between ANG and ALD (r = -0.660). The DPF was correlated with REN (r = 0.740) and with ALD (r = 0.800) concentrations. Ovulation in the mare is associated with high plasma REN concentrations, and therefore, with an activation of the RAAS. In addition, after ovulation, the sharp decrease in plasma REN and ANG concentrations might be a reflex of the modulation of the previously activated RAAS, although plasma ALD concentrations increased during this period.

Bispecific antibodies (BsAbs) represent an important advance in innovative therapeutic strategies. Among the countless formats of BsAbs, fusion with molecules such as anticalins linked to a monoclonal antibody (mAb), represents an easy and low-cost way to obtain innovative molecules. We fused an anticalin against human fibronectin to a molecule biosimilar to trastuzumab (H0) or rituximab (R0), in four different positions, two on the N terminal region of heavy or light chains and two on the C terminal region. The eight BsAbs (H family (HF) 1 to 4 and R family (RF) 1 to 4) were produced and their affinity parameters and functional properties evaluated. The presence of anticalin did not change the glycosylation of the BsAb, shape or yield. The antigenic recognition of each BsAb family, Her2 for HF1 to 4 and CD20 for RF1 to 4, was slightly decreased (HF) or absent (RF) for the anticalin N-terminal in the light chain position. The anticalin recognition of FN was slightly decreased for the HF family, but a dramatic decrease was observed for RF members with lowest affinity for RF1. Moreover, functional properties of Abs, such as CD16 activation of NK, CD32-dependent phagocytosis and FcRn transcytosis, confirmed that this anticalin position leads to less efficient BsAbs, more so for RF than HF molecules. Nevertheless, all BsAbs demonstrated affinities for CD16, CD32 and FcRn, which suggests that more than affinity for FcRs is needed for a functioning antibody. Our strategy using anticalin and Abs allows for rapid generation of BsAbs, but as suggested by our results, some positions of anticalins on Abs result in less functionality.

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BackgroundPatient adhesion to biosimilars DMARDs have become a big medico-economic issue. Indeed, savings will depend on penetration rate of biosimilars on the biologics market. Like generics, biosimilars are unknown by the general population and patients reluctance appears to be an obstacle to the diffusion of these therapeutics.ObjectivesTo assess patients‘knowledge, information and concerns about biosimilars and to identify levers and obstacles to adhesion to biosimilars prescription.MethodsNational cross-sectional study assessing information, knowledge and concerns about biosimilars of french patients treated for a rheumatism (whether they were treated by a bDMARDs or not). The data were collected from march to july 2017 by an online assessment.Results629 patients answered the assessment. 43% knew the definition of biosimilars. 65% felt unsufficiently informed about biosimilars. The principal sources of information were the rheumatologist and the patient associations. 44% of patients treated with a biosimilar were not informed before they received a biosimilar. Patients concerns focused on molecular structure (46%), efficacy (60%) and tolerance (57%) comparatively to originator bDMARDs.Receiving information about biosimilars and understanding the definition of biosimilarity were two characteristics associated with better adhesion to biosimilars. The rheumatologist was considered the most influent source of information about biosimilar. Patients trust him concerning the decision to switch from the originator biologic to its biosimilar. Patient were reluctant to substitution by the pharmacist (2%).ConclusionsBiosimilars are largely unknown by french patients at present. Information seems to be instrumental in patient adhesion to biosimilars and in the preservation of the therapeutic relationship.References[1] Jacobs I, Singh E, Sewell L, Al-Sabbagh A, Shane LG. Patient attitudes and understanding about biosimilars: an international cross-sectional survey. Patient Prefer Adherence. MAI2016;937.[2] Beck M, Michel B, Rybarczyk-Vigouret M-C, Levêque D, Sordet C, Sibilia J, et al. Rheumatologists’ Perceptions of Biosimilar Medicines Prescription: Findings from a French Web-Based Survey. BioDrugs Clin Immunother Biopharm Gene Ther. Déc2016;30(6):585–92.Disclosure of InterestNone declared