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Lessons learned from the development of oral calcitonin: the first tablet formulation of a protein in phase III clinical trials.

April 1, 2011

J Clin Pharmacol

Abstract Oral delivery of proteins has been hampered by an array of difficulties. However, promising novel oral delivery systems have been developed. 5-CNAC, formulated with the peptide salmon calcitonin, is in phase III clinical trials for the treatment of osteoporosis or osteoarthritis and could become the first marketed oral peptide. This article reviews key findings […]

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Enzyme-linked immunosorbent assay (ELISAs) for metalloproteinase derived type II collagen neoepitope, CIIM–increased serum CIIM in subjects with severe radiographic osteoarthritis.

April 1, 2011

Clin Biochem

Abstract OBJECTIVES In joint degenerative diseases, the collagens are degraded by matrix metalloproteinases and protein fragments are released to serum as potential biomarkers. METHODS A collagen type II specific neoepitope, CIIM, was identified (…RDGAAG(1053)) by mass spectrometry. Two ELISAs against the neoepitope were developed. CIIM was measured in cartilage explants in the presence or absence […]

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Measurement of matrix metalloproteinase 9-mediated collagen type III degradation fragment as a marker of skin fibrosis.

March 29, 2011

BMC Dermatol

Abstract BACKGROUND The current study utilized a Bleomycin-induced model of skin fibrosis to investigate the neo-epitope CO3-610 (KNGETGPQGP), a fragment of collagen III released during matrix metalloproteinase-9 (MMP9) degradation of the protein, we have previously described as a novel biomarker for liver fibrosis. The aim was to investigate CO3-610 levels in another well characterised model […]

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A microarray analysis of full depth knee cartilage of ovariectomized rats.

March 15, 2011

BMC Res Notes

Abstract BACKGROUND This short communication focuses the on articular cartilage and the subchondral bone, both of which play important roles in the development of osteoarthritis (OA). There are indications that estrogen-deficiency, as the post-menopausal state, accelerate the development of OA. FINDINGS We investigated, which extracellular matrix (ECM) protein, proteases and different pro-inflammatory factors was up- […]

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Diagnosis of Osteoarthritis by Cartilage Surface Smoothness Quantified Automatically from Knee MRI.

January 1, 2011

Cartilage

Abstract OBJECTIVE We investigated whether surface smoothness of articular cartilage in the medial tibiofemoral compartment quantified from magnetic resonance imaging (MRI) could be appropriate as a diagnostic marker of osteoarthritis (OA). METHOD At baseline, 159 community-based subjects aged 21 to 81 with normal or OA-affected knees were recruited to provide a broad range of OA […]

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Oral salmon calcitonin–pharmacology in osteoporosis.

November 1, 2010

Expert Opin Biol Ther

Abstract IMPORTANCE OF THE FIELD Osteoporosis is a slow progressive disease with develops over decades, and where intervention is needed for an extended number of years. This highlights the need for safe intervention possibilities, which have sustained beneficial effects post-treatment. AREAS COVERED IN THIS REVIEW Articles on salmon calcitonin appearing on Pubmed from 1960 until […]

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Novel combinations of Post-Translational Modification (PTM) neo-epitopes provide tissue-specific biochemical markers–are they the cause or the consequence of the disease?

July 1, 2010

Clin Biochem

Abstract The aim of this review is to discuss the potential usefulness of novel advances in the class of biochemical markers, neo-epitopes. Neo-epitopes are post-translational modifications (PTMs) of proteins formed by processes such as protease cleavage, citrullination, nitrosylation, glycosylation and isomerization. Each modification results from a specific local physiological or pathobiologial process. Identification of each […]

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Biochemical markers identify influences on bone and cartilage degradation in osteoarthritis–the effect of sex, Kellgren-Lawrence (KL) score, body mass index (BMI), oral salmon calcitonin (sCT) treatment and diurnal variation.

June 17, 2010

BMC Musculoskelet Disord

Abstract BACKGROUND Osteoarthritis (OA) involves changes in both bone and cartilage. These processes might be associated under some circumstances. This study investigated correlations between bone and cartilage degradation in patients with OA as a function of sex, Kellgren-Lawrence (KL) score, Body Mass Index (BMI), oral salmon calcitonin (sCT) treatment and diurnal variation. METHODS This study […]

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Aggrecanase- and matrix metalloproteinase-mediated aggrecan degradation is associated with different molecular characteristics of aggrecan and separated in time ex vivo.

May 1, 2010

Biomarkers

Abstract Aggrecan is one of the first proteins to be depleted from articular cartilage in early osteoarthritis. We investigated the molecular differences between matrix metalloproteinase (MMP)- and aggrecanase-mediated aggrecan degradation, as a consequence of their distinct time-dependent degradation profiles. Cartilage degradation was induced by cytokine stimulation in bovine articular cartilage explants and quantified by a […]

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Should biochemical markers of bone turnover be considered standard practice for safety pharmacology?

May 1, 2010

Biomarkers

Abstract The success in biomedical sciences such as genomics and proteomics is not paralleled in the medical product development methods. The consequence of this is a lack of translation into improved drug safety and efficacy. Therefore the US Food and Drug Administration (FDA) introduced the Critical Path Initiative in 2004 to modernize drug development and […]

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