Changes in glomerular thromboxane A2 receptor expression and ligand binding following immune injury

Changes in glomerular thromboxane A2 receptor expression and ligand binding following immune injury.BackgroundThromboxane (Tx) A2 is a potent vasoconstrictor eicosanoid that attains high levels within nephritic glomeruli and mediates a drop in glomerular filtration rate (GFR). In the course of nephritis, however, GFR recovers despite high intraglomerular TxA2 levels. We hypothesized that this recovery indicates a reduced responsiveness of the glomerular vasculature to TxA2, and explored whether changes in TxA2 receptor protein expression and receptor-ligand binding are underlying mechanisms.MethodsGlomerulonephritis was induced in male Sprague-Dawley rats using an antibody raised in rabbits against rat particulate glomerular basement membrane (GBM). Changes in Tx receptor levels were assessed in protein lysates of glomeruli on days 3 and 7 after a single intravenous injection of the anti-GBM antibody. Ligand-binding studies were performed at the same time points using isolated glomeruli and the TxA2 receptor ligand [3H]-SQ-29,548. GFR was measured as the clearance of endogenous creatinine.ResultsThere was a marked increase in Tx receptor protein in the lysates of nephritic glomeruli on days 3 and 7. In contrast, binding sites (Bmax) of [3H]–SQ-29,548 decreased, indicating that the excess receptor became either inaccessible to its ligand (sequestered) or desensitized. Daily administration of the Tx synthase inhibitor Furegrelate starting prior to injection of anti-GBM antibody prevented the decrease in [3H]–SQ-29,548 binding. Furegrelate treatment starting in an established stage of nephritis had no effect. In these animals, GFR was lower than nephritic controls not treated with Furegrelate.ConclusionsThese observations indicate that in the course of glomerulonephritis, there is a marked increase in glomerular Tx receptor expression. The enhanced intraglomerular TxA2 synthesis causes either a sequestration or desensitization of its receptor. As a result, access of unbound TxA2 to efferent arterioles may become facilitated, and constriction of these arterioles may preserve GFR

Percussion hemoglobinuria - a novel term for hand trauma-induced mechanical hemolysis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Extracorpuscular hemolysis caused by mechanical trauma has been well described in relation to lower extremity use, such as in soldiers and runners. Terms such as "march hemoglobinuria", "foot strike hemolysis" and "runners hemoglobinuria" have previously been coined and are easily recalled. Newer cases, however, are being identified in individuals vigorously using their upper extremities, such as drum players who use their hands to strike the instrument. Given the increased recognition of upper extremity-related mechanical hemolysis and hemoglobinuria in drummers, and the use of hand drumming worldwide, we would like introduce a novel term for this condition and call it "percussion hemoglobinuria".</p> <p>Case presentation</p> <p>A 24-year-old Caucasian man presented with reddish brown discoloration of his urine after playing the djembe drum. Urine examination after a rigorous practice session revealed blood on the dipstick, and 0 to 2 red blood cells per high power field microscopically. The urine sample was negative for myoglobulin. Other causes of hemolysis and hematuria were excluded and cessation of drum playing resulted in resolution of his symptoms.</p> <p>Conclusions</p> <p>The association of mechanical trauma-induced hemoglobinuria and playing hand percussion instruments is increasingly being recognized. We, however, feel that the true prevalence is higher than what has been previously recorded in the literature. By coining the term "percussion hemoglobinuria" we hope to raise the awareness of screening for upper extremity trauma-induced mechanical hemolysis in the evaluation of a patient with hemoglobinuria.</p

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure