New Insight into Brucella Infection and Foodborne Diseases

Brucellosis is an important zoonotic disease. More than half a million new cases from 100 countries are reported annually to the World Health Organization (WHO). The majority of patients are living in developing countries. Brucellosis is a systemic infection with a broad clinical spectrum, ranging from an asymptomatic disease to a severe and fatal illness. Clinical and laboratory features vary widely. The main presentations are acute febrile illness, localized infection, and chronic infection. Laboratory tools for diagnosis of brucellosis include culture, serology, and polymerase chain reaction (PCR). The goal of brucellosis therapy is to control the illness and prevent complications, relapses, and sequelae. Important principles of brucellosis treatment include use of antibiotics with activity in the acidic intracellular environment, use of combination regimens, and prolonged duration of treatment. This book is the result of several months of outstanding efforts by the authors and the revision of the content by experts in the field of brucellosis. This book is a valid resource and is intended for everyone interested in infectious disease to learn the most important aspects of brucellosis

Advances in Hydraulics and Hydroinformatics Volume 2

This Special Issue reports on recent research trends in hydraulics, hydrodynamics, and hydroinformatics, and their novel applications in practical engineering. The Issue covers a wide range of topics, including open channel flows, sediment transport dynamics, two-phase flows, flow-induced vibration and water quality. The collected papers provide insight into new developments in physical, mathematical, and numerical modelling of important problems in hydraulics and hydroinformatics, and include demonstrations of the application of such models in water resources engineering

Endothelin‐1 antagonism in glomerulonephritis

A common feature of glomerular disease is a protein leak into the urine. Proteinuria occurs in kidney disease and is an important risk factor for cardiovascular disease (CVD). ET‐1 is a potent vasoconstrictor/pressor peptide that is up‐regulated in CVD and many forms of inflammatory renal diseases. The actions of ET‐1 are mediated via two G‐protein coupled receptors, the ETAR which serves primarily in the pro‐hypertensive actions of ET‐1 and is often considered as the main pathological receptor subtype, with the ETBR serving to clear circulating ET‐1. Antagonism of one or both of receptors has been shown to be of clinical benefit in the treatment of hypertension. This research demonstrated a beneficial effect of selective ETAR antagonism using Sitaxsentan in a rat model of GN. ETAR blockade reduced blood pressure and importantly reduced glomerular inflammation as assessed by glomerular macrophage (Mϕ) infiltration. Further, we aimed to demonstrate that Mϕ, key mediators of inflammation are activated by ET‐1 to adopt a pro‐inflammatoy phenotype. However, early studies demonstrated that ET‐1 does not activate Mϕ as hypothesised. Mϕ were more phagocytic, and ET‐1 was chemokinetic for macrophages, an ETBR medicated event. ET‐1 was also removed by Mϕ, suggesting a potential regulatory role of Mϕ in the ET system. This phenomenon led to inclusion of additional in vivo studies to investigate the role of Mϕ in the regulation of ET‐1 and its pressor effects. These effects were investigated in a murine model of Mϕ ablation using CD11b‐DTR mice. These experiments determined in vivo that Mϕ ablation augments pressor responses to ET‐1, suggesting that Mϕ are required to regulate ET‐1. In vitro, Mϕ remove ET‐1 by several mechanisms involving proteolytic degradation of the peptide and ETBR mediated clearance, demonstrating a potential mechanism for the in vivo observation. Furthermore, proteinuria is believed to be due to damage or effacement of specialized visceral glomerular epithelial cells or podocytes. We identified in vitro that the ETAR mediates ET‐1 induced human podocyte cell effacement by actin cytoskeleton aberrations and slit‐diaphragm protein down-regulation, ET‐1 and pro‐inflammatory cytokine production. This thesis provides evidence to support our initial hypotheses that selective ETAR antagonism ameliorates proteinuric renal disease via its effects on podocytes and macrophages. Continued studies both in vitro and in vivo will strengthen the body of evidence to promote the therapeutic use of ETR antagonists in inflammatory renal disease