Current status of cadmium as an environmental health problem.

https://scholarlypublications.universiteitleiden.nl/access/item%3A3137579/view

Venous thrombosis: a multicausal disease.

International Consensus Statement on an Update of the Classification Criteria for Definite Antiphospholipid Syndrome(APS)

VTE, Thrombophilia, Antithrombotic Therapy, and Pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

Senescent cells (SnCs) accumulate in many vertebrate tissues with age and contribute to age-related pathologies, presumably through their secretion of factors contributing to the senescence-associated secretory phenotype (SASP). Removal of SnCs delays several pathologies and increases healthy lifespan. Aging and trauma are risk factors for the development of osteoarthritis (OA), a chronic disease characterized by degeneration of articular cartilage leading to pain and physical disability. Senescent chondrocytes are found in cartilage tissue isolated from patients undergoing joint replacement surgery, yet their role in disease pathogenesis is unknown. To test the idea that SnCs might play a causative role in OA, we used the p16-3MR transgenic mouse, which harbors a p16INK4a (Cdkn2a) promoter driving the expression of a fusion protein containing synthetic Renilla luciferase and monomeric red fluorescent protein domains, as well as a truncated form of herpes simplex virus 1 thymidine kinase (HSV-TK). This mouse strain allowed us to selectively follow and remove SnCs after anterior cruciate ligament transection (ACLT). We found that SnCs accumulated in the articular cartilage and synovium after ACLT, and selective elimination of these cells attenuated the development of post-traumatic OA, reduced pain and increased cartilage development. Intra-articular injection of a senolytic molecule that selectively killed SnCs validated these results in transgenic, non-transgenic and aged mice. Selective removal of the SnCs from in vitro cultures of chondrocytes isolated from patients with OA undergoing total knee replacement decreased expression of senescent and inflammatory markers while also increasing expression of cartilage tissue extracellular matrix proteins. Collectively, these findings support the use of SnCs as a therapeutic target for treating degenerative joint disease.

/pdf/local-clearance-of-senescent-cells-attenuates-the-434m3ye84t.pdf

Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment.

Haemostatic changes in pregnancy.

Toxic and essential elements in placentas of Swedish women.

The placenta constitutes a physical and immunological barrier against invading infectious agents and has been suggested to be a pregnancy-specific component of the innate immune system. The aim of this study was to investigate the presence and regulation of Toll-like receptors-2 and -4 (TLR2 and TLR4) in the human placenta, because these receptors are believed to be important for immune responses against pathogens. Twenty-eight placentas from normal term pregnancies were analysed with immunohistochemistry, which showed a strong immunoreactivity for TLR2 and TLR4 in the villous and the intermediate trophoblasts. The regulation of TLR2 and TLR4 by microbial stimulus was assessed by incubating explants of term chorionic villi with zymosan or lipopolysaccharide (LPS) and analysed with real-time reverse transcriptase-polymerase chain reaction. Stimulation with zymosan and LPS readily induced interleukin (IL)-6 and IL-8 cytokine production in the placenta cultures, whereas TLR2 and TLR4 mRNA and protein expression remained at the same high level as in unstimulated explants. These data suggests a novel mechanism for the fetoplacental unit to interact with micro-organisms.

Expression and regulation of the pattern recognition receptors Toll-like receptor-2 and Toll-like receptor-4 in the human placenta.

Objectives. The purpose of this study was to determine the impact of iron status on cadmium dose among pregnant women. Methods. Iron status and cadmium concentration in blood, urine, and placenta were determined among women followed for 2 years from early pregnancy. Results. Blood cadmium and urinary cadmium were correlated with iron status throughout the study period. Urinary cadmium increased longitudinally among women with exhausted iron stores during their pregnancy. The increase in urinary cadmium with age was more pronounced in multiparous than in nulliparous women. Conclusions. Iron deficiency during pregnancy leads to increased cadmium absorption and body burden. Multiparous women exhibit additional increases with increasing age.

Cadmium Exposure in Pregnancy and Lactation in Relation to Iron Status

Objective

To prospectively investigate the development of fetal heart block in anti–SSA/Ro 52-kd–positive women, and to evaluate the usefulness of serial Doppler echocardiography in detecting early signs of congenital heart block.



Methods

Twenty-four women with anti–SSA/Ro 52-kd antibodies and consequently increased risk for fetal heart block were followed up weekly, between 18 and 24 weeks of gestation, with two Doppler echocardiographic methods designed to estimate the time delay between hemodynamic events caused by atrial and ventricular depolarizations. Two hundred eighty-four women with normal pregnancies served as controls. Anti–Ro 52-kd, anti–Ro 60-kd, and anti-La antibodies were investigated by immunoblotting and enzyme-linked immunosorbent assay using recombinant proteins.



Results

In anti–Ro 52-kd–positive women, fetal atrioventricular (AV) time intervals were longer and heart rates were slightly lower compared with those in controls. Eight of 24 fetuses had signs of first-degree block. One of these fetuses had progression to complete block, and another showed recovery from second-degree block to first-degree block with betamethasone treatment. In the remaining 6 fetuses, spontaneous normalization occurred before or shortly after birth. Fetuses with normal AV time intervals at 18–24 weeks had normal electrocardiographic results at birth.



Conclusion

Anti–Ro 52-kd–positive pregnant women frequently carry fetuses with Doppler echocardiographic signs of first-degree AV block. These blocks revert spontaneously in the majority of fetuses, but progression to a more severe degree of block may occur in some. Serial Doppler echocardiographic measurement of AV time intervals is suggested as a useful method for surveillance of these high-risk pregnancies.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.20126

Katarina Bremme

Papers

Haemostatic changes in pregnancy.

Toxic and essential elements in placentas of Swedish women.

Expression and regulation of the pattern recognition receptors Toll-like receptor-2 and Toll-like receptor-4 in the human placenta.

Cadmium Exposure in Pregnancy and Lactation in Relation to Iron Status

Signs of first‐degree heart block occur in one‐third of fetuses of pregnant women with anti–SSA/Ro 52‐kd antibodies