Anti-THRA monoclonal antibody, clone O504/74

Thyroid hormone action is predominantly mediated by thyroid hormone receptors (THRs), which are encoded by the thyroid hormone receptor alpha (THRA) and thyroid hormone receptor beta (THRB) genes. Patients with mutations in THRB present with resistance to thyroid hormone beta (RTH beta), which is a disorder characterized by elevated levels of thyroid hormone, normal or elevated levels of TSH and goitre. Mechanistic insights about the contributions of THR beta to various processes, including colour vision, development of the cochlea and the cerebellum, and normal functioning of the adult liver and heart, have been obtained by either introducing human THRB mutations into mice or by deletion of the mouse Thrb gene. The introduction of the same mutations that mimic human THR beta alterations into the mouse Thra and Thrb genes resulted in distinct phenotypes, which suggests that THRA and THRB might have non-overlapping functions in human physiology. These studies also suggested that THRA mutations might not be lethal. Seven patients with mutations in THR alpha have since been described. These patients have RTH alpha and presented with major abnormalities in growth and gastrointestinal function. The hypothalamic-pituitary-thyroid axis in these individuals is minimally affected, which suggests that the central T-3 feedback loop is not impaired in patients with RTH alpha, in stark contrast to patients with RTH beta.

The multispiked connecting scaffold (MSC-Scaffold) prototype, inspired by the biological system of anchorage of the articular cartilage in the periarticular trabecular bone by means of subchondral bone interdigitations, is the essential innovation in fixation of the bone in resurfacing arthroplasty (RA) endoprostheses. The biomimetic MSC-Scaffold, due to its complex geometric structure, can be manufactured only using additive technology, for example, selective laser melting (SLM). The major purpose of this work is determination of constructional possibilities for the structural-geometric functionalization of SLM-manufactured MSC-Scaffold prototype, compensating the reduced ability-due to the SLM technological limitations-to accommodate the ingrowing bone filling the interspike space of the prototype, which is important for the prototype bioengineering design. Confocal microscopy scanning of components of the SLM-manufactured prototype of total hip resurfacing arthroplasty (THRA) endoprosthesis with the MSC-Scaffold was performed. It was followed by the geometric measurements of a variety of specimens designed as the fragments of the MSC-Scaffold of both THRA endoprosthesis components. The reduced ability to accommodate the ingrowing bone tissue in the SLM-manufactured prototypes versus that in the corresponding CAD models has been quantitatively determined. Obtained results enabled to establish a way of compensatory structural-geometric functionalization, allowing the MSC-Scaffold adequate redesigning and manufacturing in additive SLM technology.