45 Publication(s) found
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Bone
14. Dec 2016

High throughput, quantitative analysis of human osteoclast differentiation and activity

Osteoclasts are multinuclear cells that degrade bone under both physiological and pathophysiological conditions. Osteoclasts are therefore a major target of osteoporosis therapeutics aimed at preserving bone. Consequently, analytical methods for osteoclast activity are useful for the development of …

Central Nervous System, Alzheimer’s Disease
18. Nov 2016

Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic

The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patien…

Central Nervous System, Traumatic Brain Injury
15. Nov 2016

Serum tau fragments predict return to play in concussed professional ice hockey players

INTRODUCTION:
The diagnosis of sports-related concussion is mainly based on subjective clinical symptoms and neuropsychological tests. Thus, reliable brain injury biomarkers to assess when it is safe to return to play are highly desirable. The overall objective of this study was to evaluate the uti…

Cardiovascular System, Central Nervous System
15. Nov 2016

Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia

BACKGROUND:
The mechanisms underlying red blood cell (RBC)-mediated hypoxic vasodilation remain controversial, with separate roles for nitrite () and S-nitrosohemoglobin (SNO-Hb) widely contested given their ability to transduce nitric oxide bioactivity within the microcirculation. To establish the…

Hematology, Hemophilia
28. Oct 2016

Altered collagen turnover in factor VIII-deficient rats with hemophilic arthropathy identifies potential novel serological biomarkers in hemophilia

ESSENTIALS:
Joint bleeding in hemophilia may induce significant remodeling of the extracellular matrix. Biomarkers of collagen turnover were investigated in a F8-/- rat model of hemophilic arthropathy. Biomarkers of cartilage degradation increased significantly during development of arthropathy. B…

Oncology
26. Oct 2016

Cohort Profile: The Prospective Epidemiological Risk Factor (PERF) study

The world’s population is ageing. In Europe alone, the elderly population over age 65 will double from 88 to 153 million and the fastest growing segment of the population will be those over 80, tripling in number from 24 to 60 million in 2060. Low birth rates and increasing longevity are the key fac…

Hepatic System, Type 2-Diabetes
20. Oct 2016

Fibrogenesis assessed by serological type III collagen formation identifies patients with progressive liver fibrosis and responders to anti-fibrotic therapy

There are no approved treatments for liver fibrosis. To aid development of antifibrotic therapies, noninvasive biomarkers that can identify patients with progressive fibrosis and that permit monitoring of the response to antifibrotic therapy are much needed. Samples from a phase II antifibrotic tria…

Rheumatology, Osteoarthritis
11. Oct 2016

The association between histological, macroscopic and magnetic resonance imaging assessed synovitis in end-stage knee osteoarthritis: a cross-sectional study

OBJECTIVES:
To investigate the association between magnetic resonance imaging (MRI), macroscopic and histological assessments of synovitis in end-stage knee osteoarthritis (KOA).

METHODS:
Synovitis of end-stage osteoarthritic knees was assessed using non-contrast-enhanced (CE), contrast-enhance…

Extracellular Matrix Research, Respiratory System
4. Oct 2016

High levels of biomarkers of collagen remodeling are associated with increased mortality in COPD - results from the ECLIPSE study

BACKGROUND:
There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated with mortali…

Hepatic System, Hepatitis B/C, Extracellular Matrix Research
3. Oct 2016

Fibrosis is not just fibrosis - basement membrane modelling and collagen metabolism differs between hepatitis B- and C-induced injury

BACKGROUND:
While morphological patterns differ, the molecular phenotype of liver fibrosis is considered a stereotypical response to chronic liver injury. However, with different cellular triggers and networks regulating fibrosis, the molecular responses of the injured liver may not be identical.

Bone, Osteoporosis
1. Oct 2016

A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D

This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis. A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 to receive calcium and vitamin D …

Type 2-Diabetes
15. Sep 2016

Metabolic syndrome and subsequent risk of type 2 diabetes and cardiovascular disease in elderly women: Challenging the current definition

The prognostic value of the metabolic syndrome (MetS) is believed to vary with age. With an elderly population expecting to triple by 2060, it is important to evaluate the validity of MetS in this age group. We examined the association of MetS risk factors with later risk of type 2 diabetes (T2DM) a…

Type 2-Diabetes
8. Sep 2016

Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes

AIMS/HYPOTHESIS:
The treatment of type 2 diabetes with full peroxisome proliferator-activated receptor gamma (PPARγ) agonists improves insulin sensitivity, but is associated with weight gain, heart failure, peripheral oedema and bone loss. Endotrophin, the C-terminal fragment of the α3 chain of pro…

Respiratory System, Chronic Obstructive Pulmonary Disease
7. Sep 2016

Characterization of serological neo-epitope biomarkers reflecting collagen remodeling in clinically stable chronic obstructive pulmonary disease

OBJECTIVES:
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation that leads to excessive remodeling of the lung extracellular matrix (ECM), resulting in release of protein fragments (neo-epitopes) to the blood. Serological markers assessing this have previously been…

Bone
30. Aug 2016

Neo-epitope Peptides as Biomarkers of Disease Progression for Muscular Dystrophies and Other Myopathies

For several decades, serological biomarkers of neuromuscular diseases as dystrophies, myopathies and myositis have been limited to routine clinical biochemistry panels. Gauging the pathological progression is a prerequisite for proper treatment and therefore identifying accessible, easy to monitor b…

Chronic Obstructive Pulmonary Disease
26. Aug 2016

Systemic Biomarkers of Collagen and Elastin Turnover Are Associated With Clinically Relevant Outcomes in COPD

BACKGROUND:
Extracellular matrix (ECM) remodeling of the lung tissue releases protein fragments into the blood, where they may be detected as serologic surrogate markers of disease activity in COPD. Our goal was to assess the association of ECM turnover with severity and outcome of COPD.

METHODS…

Bone
19. Aug 2016

Regulation and Function of Lentiviral Vector-Mediated TCIRG1 Expression in Osteoclasts from Patients with Infantile Malignant Osteopetrosis: Implications for Gene Therapy

Infantile malignant osteopetrosis (IMO) is a rare, recessive disorder characterized by increased bone mass caused by dysfunctional osteoclasts. The disease is most often caused by mutations in the TCIRG1 gene encoding a subunit of the V-ATPase involved in the osteoclasts capacity to resorb bone. We …

Bone, Osteoporosis
16. Aug 2016

Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial

IMPORTANCE:
Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor.

OBJECTIVE:
To determine the efficacy and safety of abaloparatide, 80 μg, vs placebo for prevention of new vertebral fracture i…

Rheumatology, Osteoarthritis
2. Aug 2016

Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future

Osteoarthritis (OA) is the biggest unmet medical need among the many musculoskeletal conditions and the most common form of arthritis. It is a major cause of disability and impaired quality of life in the elderly. We review several ambitious but failed attempts to develop joint structure-modifying t…

Extracellular Matrix Research
1. Aug 2016

Type VIII collagen is elevated in diseases associated with angiogenesis and vascular remodeling

OBJECTIVES:
Type VIII collagen is involved in angiogenesis and remodeling of arteries. We hypothesized that type VIII collagen was upregulated in diseases associated with vascular remodeling, e.g. pulmonary fibrosis and cancer. In this paper we present the development and validation of a competiti…

Respiratory System
1. Aug 2016

Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF

RATIONALE:
Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberran…

Endocrinology, Type 2-Diabetes
1. Aug 2016

The dual amylin- and calcitonin-receptor agonist KBP-042 increases insulin sensitivity and induces weight loss in rats with obesity

OBJECTIVE:
In this study, KBP-042, a dual amylin- and calcitonin-receptor agonist, was investigated as a treatment of obesity and insulin resistance in five different doses (0.625 µg/kg-10 µg/kg) compared with saline-treated and pair-fed controls.

METHODS:
Rats with obesity received daily s.c…

Colorectal
28. Jul 2016

Excessive collagen turnover products are released during colorectal cancer progression and elevated in serum from metastatic colorectal cancer patients

During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of prote…

Extracellular Matrix Research
27. Jul 2016

Quantification of fibronectin as a method to assess ex vivo extracellular matrix remodeling

Altered architecture, composition and quality of the extracellular matrix (ECM) are pathological hallmarks of several inflammatory and fibro-proliferative pathological processes such as osteoarthritis (OA), rheumatoid arthritis (RA), fibrosis and cancer. One of the most important components of the E…

Oncology
13. Jul 2016

Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study

BACKGROUND:
An altered tumor microenvironment is one of the earliest signs of cancer and an important driver of the disease. We have seen previously that biomarkers reflecting tumor microenvironment modifications, such as matrix metalloproteinase (MMP)-degraded type 1 collagen (C1M), MMP-degraded t…

Extracellular Matrix Research, Respiratory System
5. Jul 2016

Tissue turnover of collagen type I, III and elastin is elevated in the PCLS model of IPF and can be restored back to vehicle levels using a phosphodiesterase inhibitor

BACKGROUND:
The aim of this study was to develop and validate a model for pulmonary fibrosis, using ex vivo tissue cultures of lungs from bleomycin treated animals, enabling the investigation of fibrosis remodeling using novel biomarkers for the detection of ECM protein fragments. The combination …

Rheumatology
16. Jun 2016

Chondrocyte activity is increased in psoriatic arthritis and axial spondyloarthritis

BACKGROUND:
Psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are chronic inflammatory rheumatic diseases with complex origins. Both are characterized by altered extracellular matrix remodeling in joints and entheses that results in destructive and osteochondral proliferative lesions. T…

Rheumatology
2. Jun 2016

Intercritical circulating levels of neo-epitopes reflecting matrixmetalloprotease-driven degradation as markers of gout and frequent gout attacks

OBJECTIVE:
Recurrent flares constitute the main clinical burden of gout. Our aim was to assess whether biomarkers measuring MMP tissue degradation could be used as markers of frequent gout flares.

METHODS:
Fasting plasma samples from 112 men with gout and 170 controls, along with serum samples …

Osteoporosis, Bone
1. Jun 2016

Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice

In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery …

Extracellular Matrix Research, Renal System
22. May 2016

Precision-Cut Kidney Slices as a Tool to Understand the Dynamics of Extracellular Matrix Remodeling in Renal Fibrosis

The aim of this study was to set up an ex vivo model for renal interstitial fibrosis in order to investigate the extracellular matrix (ECM) turnover profile in the fibrotic kidney. We induced kidney fibrosis in fourteen 12-week-old male Sprague Dawley rats by unilateral ureteral obstruction (UUO) su…

Rheumatology, Osteoarthritis
5. May 2016

The Need for Predictive, Prognostic, Objective and Complementary Blood-Based Biomarkers in Osteoarthritis (OA)

Osteoarthritis (OA) has traditionally been viewed as a non-inflammatory arthropathy and has not been considered a ‘serious disease’. However, this view has radically changed in recent years, due to the complexity and heterogeneity of the patient populations, spiralling socio-economical costs and lon…

Endocrinology, Type 2-Diabetes
1. May 2016

KBP-088, a novel DACRA with prolonged receptor activation, is superior to davalintide in terms of efficacy on body weight

This study aims to elucidate the mechanism behind the potent weight loss induced by dual amylin and calcitonin receptor agonists (DACRA) through comparison of the novel DACRA KBP-088 with the amylinomimetic davalintide with regard to in vitro receptor pharmacology and in vivo efficacy on food intake…

Rheumatology, Osteoarthritis
28. Apr 2016

Osteoarthritis biomarkers derived from cartilage extracellular matrix: Current status and future perspectives

Specific soluble biomarkers can be powerful tools for the diagnosis, prognosis and personalized management of osteoarthritis (OA). Biomarkers are potential indicators of the effect of a drug on cartilage metabolism and provide crucial information about the mechanisms of drug action. In this review, …

Gastrointestinal, Hernia
14. Apr 2016

Abdominal wall hernias - A local manifestation of systemically impaired quality of the extracellular matrix

BACKGROUND:
Throughout life, inguinal hernia develops in approximately every fourth man, some of whom develop multiple hernias. If patients at risk of developing multiple hernias could be identified by a serologic biomarker, treatment might be able to be tailored and improved. Evidence suggests tha…

Rheumatology, Osteoarthritis
1. Apr 2016

Association between biomarkers of tissue inflammation and progression of osteoarthritis: evidence from the Rotterdam study cohort

BACKGROUND:
We aimed to investigate the prognostic value of two biomarkers of tissue inflammation, matrix metalloproteinase-dependent degradation of C-reactive protein (CRPM) and connective tissue type I collagen turnover (C1M), on the incidence and progression of radiographic osteoarthritis (OA) i…

Rheumatology, Rheumatoid Arthritis
28. Mar 2016

Neo-Epitopes-Fragments of Cartilage and Connective Tissue Degradation in Early Rheumatoid Arthritis and Unclassified Arthritis

OBJECTIVE:
Tissue destruction in rheumatoid arthritis (RA) is predominantly mediated by matrix metalloproteinases (MMPs), thereby generating protein fragments. Previous studies have revealed that these fragments include MMP-mediated collagen type I, II, and III degradation, citrullinated and MMP-de…

Alzheimer’s Disease
1. Mar 2016

Late-Life Risk Factors for All-Cause Dementia and Differential Dementia Diagnoses in Women: A Prospective Cohort Study

Since the first evidence of a decline in dementia incidence was reported in 2011, the focus on modifiable risk factors has increased. The possibility of risk factor intervention as a prevention strategy has been widely discussed; however, further evidence in relation to risk factors is still needed.…

Rheumatology, Spondyloarthropathies
10. Feb 2016

CRP and a biomarker of type I collagen degradation, C1M, can differentiate anti-inflammatory treatment response in ankylosing spondylitis

AIM:
To investigate if tissue turnover biomarkers were efficacy biomarkers in ankylosing spondylitis and if the biomarkers at baseline predicted a good outcome (BASDAI50).

PATIENTS & METHODS:
Twenty-two etanercept treated ankylosing spondylitis patients were investigated for inflammation (CRP, …

Rheumatology, Osteoarthritis, Extracellular Matrix Research
10. Feb 2016

Synovitis biomarkers: ex vivo characterization of three biomarkers for identification of inflammatory osteoarthritis

OBJECTIVE:
Characterize biomarkers measuring extracellular matrix turnover of inflamed osteoarthritis synovium.

METHODS:
Human primary fibroblast-like synoviocytes and synovial membrane explants (SMEs) treated with various cytokines and growth factors were assessed by C1M, C3M, and acMMP3 in …

Renal System
1. Feb 2016

Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease

During chronic kidney disease (CKD) there is a dysregulation of extracellular matrix (ECM) homeostasis leading to renal fibrosis. Lysosomal proteases such as cathepsins (Cts) regulate this process in other organs, however, their role in CKD is still unknown. Here we describe a novel role for catheps…

Rheumatology, Osteoarthritis
25. Jan 2016

Osteoarthritis year in review 2015: soluble biomarkers and the BIPED criteria

OBJECTIVE:
To review and summarize biomarker data published from April 2014 to May 2015 to provide insight to the ongoing work in the field of osteoarthritis (OA). Furthermore, to summarize the BIPED criteria and set it in context of the medical needs of 2015.

METHODS:
PubMed was used as search…

Rheumatology, Rheumatoid Arthritis
20. Jan 2016

Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study

BACKGROUND:
Rheumatoid arthritis (RA) is characterized by gradual joint destruction. Tocilizumab (TCZ) significantly suppresses symptoms, however not all patients are protected from joint damage. We investigated whether early measurement of specific biomarkers could predict early joint protection r…

Bone, Osteoporosis
6. Jan 2016

Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures

Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, re…

Clinical Data Quality
4. Jan 2016

The impact of clinical trial monitoring approaches on data integrity and cost-a review of current literature

PURPOSE:
Monitoring is a costly requirement when conducting clinical trials. New regulatory guidance encourages the industry to consider alternative monitoring methods to the traditional 100 % source data verification (SDV) approach. The purpose of this literature review is to provide an overview o…