1,720,992 research outputs found
Surface Plasmon Resonance analysis of HIV-1 gp 120 binding to muscle nicotinic receptors
No full textA novel ex vivo organotypic culture model of alkaptonuria-ochronosis
No full textOBJECTIVES: Alkaptonuria (AKU) is an orphan disease that has an estimated prevalence of 0.3/100,000. The disease is caused by the lack of activity of homogentisic acid oxidase (HGO), an enzyme involved in tyrosine and phenylalanine metabolism. To date, there is only one drug, the nitisinone, with orphan designation authorised by both Food and Drug Administration (FDA) and European Medical Agency (EMA) for AKU. A clinical trial on AKU patients using nitisinone has recently been completed but it needs further investigation for long-term therapy. In recent years our group has developed a series of AKU in vitro models using cell lines, primary chondrocytes and human plasma in order to test the efficacy of new substances, mainly antioxidant compounds, for AKU therapy. Herein, we report the optimisation of an ex vivo reproducible culture method exploiting cartilage slices in order to investigate the deposition of ochronotic pigment in this kind of connective tissue.
METHODS: Human normal cartilage slices, obtained after surgery for prosthesis replacement, were cultured for several days in the presence of a sublethal concentration of homogentisic acid (HGA).
RESULTS: After two months of incubation with HGA, the peculiar melanin-like ochronotic pigmentation can be observed into the cartilage tissue.
CONCLUSIONS: This novel organo-typic ex vivo model could be extremely useful to investigate the efficacy of substances able to ameliorate the conditions of AKU patients. Moreover, it could be used for genetic and proteomic investigations to better define AKU pathophysiology
IDENTIFICATION OF OSTEOBLAST CELLS DIFFERENTIATION AND BONE TUMOR MARKERS AND USES THEREOF
No full textHuman platelet releasates combined with polyglycolic acid scaffold promote chondrocyte differentiation and phenotypic maintenance
No full textin the present study, we aimed to demonstrate the differentiating properties of platelet-rich plasma releasates (PRPr) on human chondrocytes seeded on a polygtlycolic acid (PGA) 3D scaffold. Gene expression and biochemical analysis were carried out to assess the improved quality of our PGA-based cartilage constructs supplemented with PRPr. We observed that the use of PRPr as cell cultures supplementation to PGA-chondrocyte constructs may promote chondrocyte differentiation, and thus may contribute to maintaining the chondrogenic phenotype longer than conventional supplementation by increasing high levels of important chondrogenic markers (e.g. sox9, aggrecan and type II collagen), without induction of type I collagen. Moreover, our constructs were analysed for the secretion and deposition of important ECM molecules (sGAG, type II collagen, etc.). Our results indicate that PRPr supplementation may synergize with PGA-based scaffolds to stimulate human articular chondrocyte differentiation, maturation and phenotypic maintenance
Post-genomics of bone metabolic dysfunctions and neoplasias
No full textPost-genomic research on osteoblastic and osteoclastic cells, in contrast to that on many other cell types, has only been undertaken recently. Nevertheless, important information has been gained from these investigations on the mechanisms involved in osteoblast differentiation and on markers relevant for tissue regeneration and therapeutic validation of drugs, hormones and growth factors. These protein indicators may also have a diagnostic and prognostic value for bone dysfunctions and tumors. Some reviews have already focused on the application of transcriptomics and/or proteomics for exploring skeletal biology and related disorders. The main goal of the present review is to systematically summarize the most relevant post-genomic studies on various metabolic bone diseases (osteoporosis, Paget's disease and osteonecrosis), neoplasias (osteosarcoma) and metabolic conditions that indirectly affect bone tissue, such as alkaptonuria
Structural studies on functionally equivalent regions in different post-synaptic neurotoxins
No full textHLA class I expression on human platelets is highly variable and correlates with distinct allele group frequencies
Full text linkBackground: Human leukocyte antigen (HLA) class I molecules are expressed on platelets and can represent a source of alloimmunization in recipients of platelet transfusions. HLA mismatch between donors and recipients may be associated with the induction of anti-HLA antibodies, which can culminate in refractoriness to platelet transfusions. In the present study we analyzed HLA allele group frequencies and HLA expression levels on human platelets from blood donors.
Materials and methods: Platelet-rich plasma was collected from 139 donors to monitor platelet HLA class I expression by flow cytometry. DNA from donors with high and low platelet HLA expression was used in the genotype studies. Frequencies of large and normal-sized platelet subpopulations were determined and HLA class I expression was studied. Mean platelet volume (MPV) and platelet large-cell ratio (P-LCR) were analyzed in both groups of donors.
Results: The analysis showed variable platelet HLA class I expression with significant differences among donors. HLA class I allele group frequencies in donors with high and low platelet HLA expression showed distinctive genotypic features strictly related to expression level. The main allele groups found in samples with high platelet HLA class I expression were HLA-A*02, -A*68, -B*15, -B*49, and -C*03. Platelet HLA class I expression did not change over time or during freezing-thawing cycles. The analysis of platelet subpopulations showed a statistically significant higher expression of HLA class I molecules on large platelets than on normal-sized platelets. Moreover, donors with high HLA class I expression showed a higher frequency of large platelets (p<0.0001). The analysis of P-LCR in both groups of donors showed a statistically significant difference (p<0.05) within high HLA-expressing donors.
Discussion: Our data suggest an allele-dependent expression of HLA class I molecules on human platelets with distinct HLA allele group frequencies and different platelet subpopulation frequencies among blood donors
Platelet derived growth factors enhance proliferation and differentiation of human articular chondrocytes
No full textRole of apoptosis in osteoporosis induced by glucocorticoids
No full textGlucocorticoid (GC)-induced osteoporosis (GIO) is a common and serious complication of prolonged systemic GC use. Bone loss with risk of fractures resulting from GC therapy is a relatively common disorder, and is the most prevalent form of secondary osteoporosis. It is generally accepted that GC can cause a rapid bone loss, decreasing bone formation and increasing bone resorption in vitro as well as in vivo. The decrease in bone formation has been mainly attributed to GC effects on osteoblastogenesis and osteocyte apoptosis, while the increase in bone resorption has been referred to an extension of the life-span of pre-existing osteoclasts. This article focuses on newer molecular aspects regarding the apoptotic mechanisms involved in the pathogenesis of GIO and is based on a presentation that was held at the 3rd Congresso Nazionale in Osteoporosi Secondarie e Endocrinopatie, in Ancona, Italy, October 2007
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