Histopathological Changes in the Kidney following Congestive Heart Failure by Volume Overload in Rats

Background. This study investigated histopathological changes and apoptotic factors that may be involved in the renal damage caused by congestive heart failure in a rat model of infrarenal aortocaval fistula (ACF). Methods. Heart failure was induced using a modified approach of ACF in male Wistar rats. Sham-operated controls and ACF rats were characterized by their morphometric and hemodynamic parameters and investigated for their histopathological, ultrastructural, and apoptotic factor changes in the kidney. Results. ACF- induced heart failure is associated with histopathological signs of congestion and glomerular and tubular atrophy, as well as nuclear and cellular degeneration in the kidney. In parallel, overexpression of proapoptotic Bax protein, release of cytochrome C from the outer mitochondrial membrane into cell cytoplasm, and nuclear transfer of activated caspase 3 indicate apoptotic events. This was confirmed by electron microscopic findings of apoptotic signs in the kidney such as swollen mitochondria and degenerated nuclei in renal tubular cells. Conclusions. This study provides morphological evidence of renal injury during heart failure which may be due to caspase-mediated apoptosis via overexpression of proapoptotic Bax protein, subsequent mitochondrial cytochrome C release, and final nuclear transfer of activated caspase 3, supporting the notion of a cardiorenal syndrome

Prostanoid Receptor Subtypes and Its Endogenous Ligands with Processing Enzymes within Various Types of Inflammatory Joint Diseases

A complex inflammatory process mediated by proinflammatory cytokines and prostaglandins commonly occurs in the synovial tissue of patients with joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). This study systematically investigated the distinct expression profile of prostaglandin E2 (PGE2), its processing enzymes (COX-2), and microsomal PGES-1 (mPGES-1) as well as the corresponding prostanoid receptor subtypes (EP1-4) in representative samples of synovial tissue from these patients (JT, OA, and RA). Quantitative TaqMan®-PCR and double immunofluorescence confocal microscopy of synovial tissue determined the abundance and exact immune cell types expressing these target molecules. Our results demonstrated that PGE2 and its processing enzymes COX-2 and mPGES-1 were highest in the synovial tissue of RA, followed by the synovial tissue of OA and JT patients. Corresponding prostanoid receptor, subtypes EP3 were highly expressed in the synovium of RA, followed by the synovial tissue of OA and JT patients. These proinflammatory target molecules were distinctly identified in JT patients mostly in synovial granulocytes, in OA patients predominantly in synovial macrophages and fibroblasts, whereas in RA patients mainly in synovial fibroblasts and plasma cells. Our findings show a distinct expression profile of EP receptor subtypes and PGE2 as well as the corresponding processing enzymes in human synovium that modulate the inflammatory process in JT, OA, and RA patients

Painful inflammation-induced increase in opioid receptor binding and G-protein coupling in primary afferent neurons

ABSTRACT Opioids mediate their analgesic effects by activating -opioid receptors (MOR) not only within the central nervous system but also on peripheral sensory neurons. The peripheral analgesic effects of opioids are best described under inflammatory conditions (e.g., arthritis). The present study investigated the effects of inflammation on MOR binding and G-protein coupling of full versus partial MOR agonists in dorsal root ganglia (DRG) of primary afferent neurons. Our results show that Freund's complete adjuvant (FCA) unilateral hindpaw inflammation induces a significant up-regulation of MOR binding sites (25 to 47 fmol/mg of protein) on DRG membranes without affecting the affinity of either full or partial MOR agonists. In our immunohistochemical studies, the number of MOR-immunoreactive neurons consistently increased. This increase was mostly caused by small-diameter nociceptive DRG neurons. The full agonist DAMGO induced MOR G-protein coupling in DRG of animals without FCA inflammation (EC 50 ϭ 56 nM; relative E max ϭ 100%). FCA inflammation resulted in significant increases in DAMGO-induced MOR G-protein coupling (EC 50 ϭ 29 nM; relative E max ϭ 145%). The partial agonist buprenorphine hydrochloride (BUP) showed no detectable G-protein coupling in DRG of animals without FCA inflammation; however, partial agonist activity of BUP-induced MOR G-protein coupling was detectable in animals with FCA inflammation (EC 50 ϭ 1.6 nM; relative E max ϭ 82%). In behavioral studies, administration of BUP produced significant antinociception only in inflamed but not in noninflamed paws. These findings show that inflammation causes changes in MOR binding and G-protein coupling in primary afferent neurons. They further underscore the important differences in clinical studies testing peripherally active opioids in inflammatory painful conditions. Opioid analgesia is not mediated exclusively within the central nervous system but also in the periphery. This has been shown in many animal models, including unilateral hindpaw inflammation induced by intraplantar injection of Freund's complete adjuvant (FCA) Materials and Method

Pathological alterations in liver injury following congestive heart failure induced by volume overload in rats

Heart failure has emerged as a disease with significant public health implications. Following progression of heart failure, heart and liver dysfunction are frequently combined in hospitalized patients leading to increased morbidity and mortality. Here, we investigated the underlying pathological alterations in liver injury following heart failure. Heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. Sham operated and ACF rats were compared for their morphometric and hemodynamic data, for histopathological and ultrastructural changes in the liver as well as differences in the expression of apoptotic factors. ACF-induced heart failure is associated with light microscopic signs of apparent congestion of blood vessels, increased apoptosis and breakdown of hepatocytes and inflammatory cell inifltration were observed. The glycogen content depletion associated with the increased hepatic fibrosis, lipid globule formation was observed in ACF rats. Moreover, cytoplasmic organelles are no longer distinguishable in many ACF hepatocytes with degenerated fragmented rough endoplasmic reticulum, shrunken mitochondria and heavy cytoplasm vacuolization. ACF is associated with the upregulation of the hepatic TUNEL-positive cells and proapoptotic factor Bax protein concomitant with the mitochondrial leakage of cytochrome C into the cell cytoplasm and the transfer of activated caspase 3 from the cytoplasm into the nucleus indicating intrinsic apoptotic events. Taken together, the results demonstrate that ACF-induced congestive heart failure causes liver injury which results in hepatocellular apoptotic cell death mediated by the intrinsic pathway of mitochondrial cytochrome C leakage and subsequent transfer of activated caspase 3 into to the nucleus to initiate overt DNA fragmentation and cell death

Meeting sustainable development goals via robotics and autonomous systems

Robotics and autonomous systems are reshaping the world, changing healthcare, food production and biodiversity management. While they will play a fundamental role in delivering the UN Sustainable Development Goals, associated opportunities and threats are yet to be considered systematically. We report on a horizon scan evaluating robotics and autonomous systems impact on all Sustainable Development Goals, involving 102 experts from around the world. Robotics and autonomous systems are likely to transform how the Sustainable Development Goals are achieved, through replacing and supporting human activities, fostering innovation, enhancing remote access and improving monitoring. Emerging threats relate to reinforcing inequalities, exacerbating environmental change, diverting resources from tried-and-tested solutions and reducing freedom and privacy through inadequate governance. Although predicting future impacts of robotics and autonomous systems on the Sustainable Development Goals is difficult, thoroughly examining technological developments early is essential to prevent unintended detrimental consequences. Additionally, robotics and autonomous systems should be considered explicitly when developing future iterations of the Sustainable Development Goals to avoid reversing progress or exacerbating inequalities

Meeting sustainable development goals via robotics and autonomous systems

Robotics and autonomous systems are reshaping the world, changing healthcare, food production and biodiversity management. While they will play a fundamental role in delivering the UN Sustainable Development Goals, associated opportunities and threats are yet to be considered systematically. We report on a horizon scan evaluating robotics and autonomous systems impact on all Sustainable Development Goals, involving 102 experts from around the world. Robotics and autonomous systems are likely to transform how the Sustainable Development Goals are achieved, through replacing and supporting human activities, fostering innovation, enhancing remote access and improving monitoring. Emerging threats relate to reinforcing inequalities, exacerbating environmental change, diverting resources from tried-and-tested solutions and reducing freedom and privacy through inadequate governance. Although predicting future impacts of robotics and autonomous systems on the Sustainable Development Goals is difficult, thoroughly examining technological developments early is essential to prevent unintended detrimental consequences. Additionally, robotics and autonomous systems should be considered explicitly when developing future iterations of the Sustainable Development Goals to avoid reversing progress or exacerbating inequalities

WiP abstract: Optimal multi-agent path planning for fast inverse modeling in UAV-based flood sensing applications

Floods are one of the most commonly occurring natural disasters, and caused more than 120,000 fatalities in the world between 1991 and 2005. Most of these casualties are caused by the lack of a reliable real-time flash flood monitoring system. Given the area to monitor, unmanned aerial vehicles (UAVs) appear as the most promising solutions for this task. © 2014 IEEE

Optimal multi-agent path planning for fast inverse modeling in UAV-based flood sensing applications

Floods are the most common natural disasters, causing thousands of casualties every year in the world. In particular, flash flood events are particularly deadly because of the short timescales on which they occur. Unmanned air vehicles equipped with mobile microsensors could be capable of sensing flash floods in real time, saving lives and greatly improving the efficiency of the emergency response. However, of the main issues arising with sensing floods is the difficulty of planning the path of the sensing agents in advance so as to obtain meaningful data as fast as possible. In this particle, we present a fast numerical scheme to quickly compute the trajectories of a set of UAVs in order to maximize the accuracy of model parameter estimation over a time horizon. Simulation results are presented, a preliminary testbed is briefly described, and future research directions and problems are discussed. © 2014 IEEE

Neuronal aldosterone elicits a distinct genomic response in pain signaling molecules contributing to inflammatory pain

Background: Recently, mineralocorticoid receptors (MR) were identified in peripheral nociceptive neurons, and their acute antagonism was responsible for immediate and short-lasting (non-genomic) antinociceptive effects. The same neurons were shown to produce the endogenous ligand aldosterone by the enzyme aldosterone synthase. Methods: Here, we investigate whether endogenous aldosterone contributes to inflammation-induced hyperalgesia via the distinct genomic regulation of specific pain signaling molecules in an animal model of Freund's complete adjuvant (FCA)-induced hindpaw inflammation. Results: Chronic intrathecal application of MR antagonist canrenoate-K (over 4 days) attenuated nociceptive behavior in rats with FCA hindpaw inflammation suggesting a tonic activation of neuronal MR by endogenous aldosterone. Consistently, double immunofluorescence confocal microscopy showed abundant co-localization of MR with several pain signaling molecules such as TRPV1, CGRP, Nav1.8, and trkA whose enhanced expression of mRNA and proteins during inflammation was downregulated following i.t. canrenoate-K. More importantly, inhibition of endogenous aldosterone production in peripheral sensory neurons by continuous intrathecal delivery of a specific aldosterone synthase inhibitor prevented the inflammation-induced enhanced transcriptional expression of TRPV1, CGRP, Nav1.8, and trkA and subsequently attenuated nociceptive behavior. Evidence for such a genomic effect of endogenous aldosterone was supported by the demonstration of an enhanced nuclear translocation of MR in peripheral sensory dorsal root ganglia (DRG) neurons. Conclusion: Taken together, chronic inhibition of local production of aldosterone by its processing enzyme aldosterone synthase within peripheral sensory neurons may contribute to long-lasting downregulation of specific pain signaling molecules and may, thus, persistently reduce inflammation-induced hyperalgesia