Bone mineral density in adult thalassaemias: a retrospective longitudinal study.

Objectives: In this study, we aim to evaluate the long-term impact of thalassaemia on bone mineral density (BMD) through sequential analysis, compare changes in BMD values between male and female patients and find any correlation between BMD and biochemical markers in the adult thalassaemia group. BMD is a bone mineral density test using dual-energy X-ray to measure calcium hydroxyapatite per unit of bone, reflecting bone strength.

Methods: We conducted a longitudinal retrospective observational cohort study to determine the changes in BMD values and biochemical parameters in adult thalassaemia patients.

Dysnatremia is a Predictor for Morbidity and Mortality in Hospitalized Patients with COVID-19.

Context: Dysnatremia is an independent predictor of mortality in patients with bacterial pneumonia. There is paucity of data about the incidence and prognostic impact of abnormal sodium concentration in patients with coronavirus disease 2019 (COVID-19).

Objective: This work aimed to examine the association of serum sodium during hospitalization with key clinical outcomes, including mortality, need for advanced respiratory support and acute kidney injury (AKI), and to explore the role of serum sodium as a marker of inflammatory response in COVID-19.

Accelerating functional gene discovery in osteoarthritis.

Osteoarthritis causes debilitating pain and disability, resulting in a considerable socioeconomic burden, yet no drugs are available that prevent disease onset or progression. Here, we develop, validate and use rapid-throughput imaging techniques to identify abnormal joint phenotypes in randomly selected mutant mice generated by the International Knockout Mouse Consortium. We identify 14 genes with functional involvement in osteoarthritis pathogenesis, including the homeobox gene Pitx1, and functionally characterize 6 candidate human osteoarthritis genes in mouse models.

Quantitative X-Ray Imaging of Mouse Bone by Faxitron.

This chapter describes the use of point projection digital microradiography for rapid imaging and quantitation of bone mineral content in mice.

Real-life experience of tolvaptan use in the treatment of severe hyponatraemia due to syndrome of inappropriate antidiuretic hormone secretion.

Objective: European guidelines do not recommend tolvaptan for treatment of syndrome of inappropriate antidiuretic hormone secretion (SIADH), principally owing to concerns about risk of overly rapid correction of hyponatraemia. This study evaluated the real-life effectiveness and safety of tolvaptan.

Design: Consecutive case series.

Adult mice lacking the type 2 iodothyronine deiodinase have increased subchondral bone but normal articular cartilage.

Background: Although osteoarthritis (OA) is the commonest joint disorder and has a rising prevalence as the population ages, no drugs are available that prevent or delay the onset and progression of disease. Recent studies identified the DIO2 gene encoding type 2 deiodinase (D2) as a susceptibility locus for OA, and further data suggest deiodinase-regulated local availability of triiodothyronine (T3) in the joint plays an important role in cartilage maintenance and repair. To investigate the hypothesis that reduced tissue T3 availability protects joints from development of OA, the joint phenotypes of adult mice lacking D2 (D2KO) or lacking both D1 and D2 (D1D2KO), the only enzymes that catalyze conversion of the prohormone thyroxine to active T3, were determined.

THRA and DIO2 mutations are unlikely to be a common cause of increased bone mineral density in euthyroid post-menopausal women.

Objective: A new autosomal dominant disorder due to mutation of THRA, which encodes thyroid hormone receptor α, is characterised by severely delayed skeletal development but only slightly abnormal thyroid status. Adult mice with disrupted thyroid hormone action in bone due to a mutation of Thra or deletion of Dio2, encoding the type 2 deiodinase, have high bone mass and mineralisation despite essentially euthyroid status. No individuals with DIO2 mutations have been described and the adult phenotype of patients with THRA mutations is largely unknown.

Thyroid hormone metabolism in skeletal development and adult bone maintenance.

Metabolism of thyroid hormones by the type 2 and type 3 iodothyronine deiodinases (D2, D3) in T3-responsive target cells is a sophisticated mechanism that helps to maintain local T3 concentrations and facilitates T3 action in a cell-specific manner that is independent of circulating thyroid hormone concentrations. Recent findings have demonstrated an essential physiological role for the thyroid hormone-activating enzyme D2 in the optimization of bone mineralization and strength. Emerging population studies have also identified the genes encoding D2 and the thyroid hormone-inactivating enzyme D3 as susceptibility loci for osteoarthritis.

Active matrix metalloproteinase-2 promotes apoptosis of hepatic stellate cells via the cleavage of cellular N-cadherin.

Background And Aims: Hepatic stellate cells (HSC) are known to synthesise excess matrix that characterises liver fibrosis and cirrhosis. Activated HSC express the matrix-degrading matrix metalloproteinase enzymes (MMPs) and their tissue inhibitors (TIMPs). During spontaneous recovery from experimental liver fibrosis, the expression of TIMP-1 declines and hepatic collagenolytic activity increases.

N-Cadherin cleavage during activated hepatic stellate cell apoptosis is inhibited by tissue inhibitor of metalloproteinase-1.

Apoptosis of hepatic stellate cells (HSC) has previously been shown to occur during spontaneous resolution of experimental liver fibrosis. TIMP-1 has also been shown to have a key role because of its ability to inhibit apoptosis of HSC via matrix metalloproteinase (MMP) inhibition. This has led to further study of novel substrates for MMPs that might impact on HSC survival.