by Keyword: Arthritis

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Matera, Carlo, Gomila-Juaneda, Alexandre, Camarero, Núria, Libergoli, Michela, Soler, Concepció, Gorostiza, Pau, (2018). A photoswitchable antimetabolite for targeted photoactivated chemotherapy Journal of the American Chemical Society 140, (46), 15764-15773

The efficacy and tolerability of systemically administered anticancer agents are limited by their off-target effects. Precise spatiotemporal control over their cytotoxic activity would allow improving chemotherapy treatments, and light-regulated drugs are well suited to this purpose. We have developed phototrexate, the first photoswitchable inhibitor of the human dihydrofolate reductase (DHFR), as a photochromic analog of methotrexate, a widely prescribed chemotherapeutic drug to treat cancer and psoriasis. Quantification of the light-regulated DHFR enzymatic activity, cell proliferation, and in vivo effects in zebrafish show that phototrexate behaves as a potent antifolate in its photoactivated cis configuration, and that it is nearly inactive in its dark-relaxed trans form. Thus, phototrexate constitutes a proof-of-concept to design light-regulated cytotoxic small molecules, and a step forward to develop targeted anticancer photochemotherapies with localized efficacy and reduced adverse effects.

Keywords: Photopharmacology, Photodynamic therapy, Antiproliferative, Arthritis, Psoriasis, Nanomedicine

Sánchez Egea, Antonio J., Valera, Marius, Parraga Quiroga, Juan Manuel, Proubasta, Ignasi, Noailly, J., Lacroix, Damien, (2014). Impact of hip anatomical variations on the cartilage stress: A finite element analysis towards the biomechanical exploration of the factors that may explain primary hip arthritis in morphologically normal subjects Clinical Biomechanics , 29, (4), 444-450

AbstractBackground Hip arthritis is a pathology linked to hip-cartilage degeneration. Although the aetiology of this disease is not well defined, it is known that age is a determinant risk factor. However, hip arthritis in young patients could be largely promoted by biomechanical factors. The objective of this paper is to analyze the impact of some normal anatomical variations on the cartilage stress distributions numerically predicted at the hip joint during walking. Methods A three-dimensional finite element model of the femur and the pelvis with the most relevant axial components of muscle forces was used to simulate normal walking activity. The hip anatomical condition was defined by: neck shaft angle, femoral anteversion angle, and acetabular anteversion angle with a range of 110-130º, 0-20º, and 0-20º, respectively. The direct boundary method was used to simulate the hip contact. Findings The hydrostatic stress found at the cartilage and labrum showed that a ± 10º variation with respect to the reference brings significant differences between the anatomic models. Acetabular anteversion angle of 0º and femoral anteversion angle of 0º were the most affected anatomical conditions with values of hydrostatic stress in the cartilage near 5 MPa under compression. Interpretation Cartilage stresses and contact areas were equivalent to the results found in literature and the most critical anatomical regions in terms of tissue loads were in a good accordance with clinical evidence. Altogether, results showed that decreasing femoral or acetabular anteversion angles isolately causes a dramatic increase in cartilage loads.

Keywords: Hip arthritis, Neck shaft angle, Femoral and acetabular anteversions, Cartilage load, Hip joint contact, Finite element analysis