scholarly journals Metabolically active and polyploid renal tissues rely on graded cytoprotection to drive developmental and homeostatic stress resilience

Development ◽  
2021 ◽  
Vol 148 (8) ◽  
Author(s):  
Katie Burbridge ◽  
Jack Holcombe ◽  
Helen Weavers

ABSTRACT Body tissues are frequently exposed to stress, from toxic byproducts generated during cellular metabolism through to infection or wounding. Although it is well-established that tissues respond to exogenous injury by rapidly upregulating cytoprotective machinery, how energetically demanding tissues – vulnerable to persistent endogenous insult – withstand stress is poorly understood. Here, we show that the cytoprotective factors Nrf2 and Gadd45 act within a specific renal cell subtype, the energetically and biosynthetically active ‘principal’ cells, to drive stress resilience during Drosophila renal development and homeostasis. Renal tubules lacking Gadd45 exhibit striking morphogenetic defects (with cell death, inflammatory infiltration and reduced ploidy) and accumulate significant DNA damage in post-embryonic life. In parallel, the transcription factor Nrf2 is active during periods of intense renal physiological activity, where it protects metabolically active renal cells from oxidative damage. Despite its constitutive nature, renal cytoprotective activity must be precisely balanced and sustained at modest sub-injury levels; indeed, further experimental elevation dramatically perturbs renal development and function. We suggest that tissues requiring long-term protection must employ restrained cytoprotective activity, whereas higher levels might only be beneficial if activated transiently pre-emptive to exogenous insult.

2019 ◽  
Vol 128 (08) ◽  
pp. 512-519 ◽  
Author(s):  
Nandini D. P. K. Manne ◽  
Gautam Kumar Ginjupalli ◽  
Kevin M. Rice ◽  
Ravikumar Arvapalli ◽  
Vincent A. Graffeo ◽  
...  

Abstract Introduction Empagliflozin, a known inhibitor of sodium-glucose cotransporter type 2 (SGLT2) decreases glucose reabsorption by the renal tubules and promotes glucose excretion into the urine. While the effectiveness of Empagliflozin in the management of hyperglycemia along with associated cardiovascular and all-cause mortality has been demonstrated previously, the therapeutic benefits associated with the long-term use of this drug in obese animals have yet to be investigated. Methods Male 5-week-old lean and obese Zucker rats were randomly assigned to one of the 4 groups- lean control, lean treated, obese control, obese treated and treated with either Empagliflozin (10 mg/kg BW / day) or placebo for 25 weeks to investigate the therapeutic effect of Empagliflozin. Results Empagliflozin treatment in the obese animals was associated with decreased body weight, attenuated the loss of F-actin from the renal tubules and improved renal structure and function. These changes in renal function were associated with significant improvements in the glucose tolerance, and decreased non-fasting circulatory levels of glucose, amylase, and other inflammatory markers including NGAL, cystatin C, and clusterin. Conclusion Long-term use of Empagliflozin in diabetic obese Zucker rats is associated with improvements in glucose tolerance and decreased loss of renal structure and function.


Author(s):  
Robert Stojanov ◽  
Sarah Rosengaertner ◽  
Alex de Sherbinin ◽  
Raphael Nawrotzki

AbstractDevelopment cooperation actors have been addressing climate change as a cross-cutting issue and investing in climate adaptation projects since the early 2000s. More recently, as concern has risen about the potential impacts of climate variability and change on human mobility, development cooperation actors have begun to design projects that intentionally address the drivers of migration, including climate impacts on livelihoods. However, to date, we know little about the development cooperation’s role and function in responding to climate related mobility and migration. As such, the main aim of this paper is to outline the policy frameworks and approaches shaping development cooperation actors’ engagement and to identify areas for further exploration and investment. First, we frame the concept of climate mobility and migration and discuss some applicable policy frameworks that govern the issue from various perspectives; secondly, we review the toolbox of approaches that development cooperation actors bring to climate mobility; and third, we discuss the implications of the current Covid-19 pandemic and identify avenues for the way forward. We conclude that ensuring safe and orderly mobility and the decent reception and long-term inclusion of migrants and displaced persons under conditions of more severe climate hazards, and in the context of rising nationalism and xenophobia, poses significant challenges. Integrated approaches across multiple policy sectors and levels of governance are needed. In addition to resources, development cooperation actors can bring data to help empower the most affected communities and regions and leverage their convening power to foster more coordinated approaches within and across countries.


2020 ◽  
Vol 28 (1) ◽  
pp. 230949901989061
Author(s):  
Suroosh Madanipour ◽  
Aditya Prinja ◽  
Marcus Lee ◽  
Abbas Rashid

There is limited literature to guide shoulder surgeons in the management of juvenile idiopathic arthritis (JIA). We aim to help clinicians to formulate an approach to the surgical management of the condition through a review of the available literature on arthroplasty in JIA, general considerations when operating on patients with inflammatory arthropathy and recommendations based on the authors’ experience. Four articles report formal data on arthroplasty in JIA with favourable improvements in post-operative pain and function scores after the long-term follow-up. Significant heterogeneity in treatment and a lack of standardisation in quantitative outcomes highlights the need for further larger scale and higher quality research. The aim of this study is to review the evidence and provide information on preoperative evaluation of surgical candidates, operative techniques, choice of implant design and to evaluate functional outcomes in patients who undergo shoulder arthroplasty.


AIDS ◽  
2010 ◽  
Vol 24 (10) ◽  
pp. 1455-1460 ◽  
Author(s):  
Giulia Marchetti ◽  
Lidia Gazzola ◽  
Daria Trabattoni ◽  
Francesca Bai ◽  
Giuseppe Ancona ◽  
...  

Author(s):  
Margit V. Szabari ◽  
Jozsef Tolnai ◽  
Balazs Maar ◽  
Harikrishnan Parameswaran ◽  
Elizabeth Bartolak-Suki ◽  
...  

The Condor ◽  
1992 ◽  
Vol 94 (1) ◽  
pp. 83-92 ◽  
Author(s):  
Gaetan Lefebvre ◽  
Brigitte Poulin ◽  
Raymond McNeil

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Aline M De Souza ◽  
Jonathas Almeida ◽  
Nataliia Shults ◽  
Hong Ji ◽  
Kathryn Sandberg

Severe caloric restriction (sCR) increases the risk for acute cardiovascular disease. Less understood are the long-term effects on cardiovascular disease risk after the sCR period has ended. We investigated the effects of sCR on heart structure and function months after refeeding (sCR-Refed). Female Fischer rats (3-months-old) were maintained on (CT) ad libitum or a 60% caloric restricted diet for 2 weeks. Thereafter, all rats received ad libitum chow for 3 months and they were analyzed by precision ultrasound to assess their heart function. After imaging, the animals were sacrificed and the hearts were subjected to ischemia-reperfusion (I/R) using a Langendorff preparation. After 2 weeks of sCR, rats lost 15% of their initial body weight (BW) [% (100*(Final-Initial/Initial)): CT, 1.5±0.8 vs sCR, -15.4±1.1; p<0.001;n=8]. After 3 months of refeeding, there was no detectable difference in BW between CT and sFR-Refed groups. Isolated hearts from the sCR-Refed rats exhibited worse myocardial pathology after I/R compared to CT rats. The parallel orientation of myofibers and striations normally present in cardiomyocytes was lost in sCR-Refed rats. Further analysis revealed uneven blood-filling of the microcirculatory vessels and prominent interstitial edema of the myocardium. Hearts from sCR-Refed rats had more atrophied cardiomyocytes than CT [Atrophied/Total (%): CT, 0.2±0.1 vs sCR-Refed, 50.6±1.1; p<0.001; n=5]. The number of arrhythmic events during a 30 min ischemic interval in isolated hearts doubled after 2 weeks on the sCR diet ( data not shown ) and remained doubled 3 months later [Arrhythmias (% of time): CT, 34±8 vs sCR-Refed, 68±9; p=0.02; n=8]. Ultrasound imaging showed no difference in stroke volume, coronary perfusion pressure and left ventricular mass. However, the thickness of the left ventricular posterior wall was significantly reduced in sCR-Refed rats [(mm): CT, 2.55 ±0.03 vs sCR-Refed, 2.10±0.04; p=0.002; n=4]. These findings indicate heart structure and function remained damaged months after the sCR period ended and BW was restored. These studies have adverse cardiovascular risk implications for who are subjected either voluntarily (crash diets) or involuntarily (very low food security) to periods of inadequate caloric intake.


2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Peter Nordbeck ◽  
Leoni Bönhof ◽  
Karl-Heinz Hiller ◽  
Sabine Voll ◽  
Paula Arias ◽  
...  

Background: Surgical procedures in small animal models of heart disease, such as artificial ligation of the coronary arteries for experimental myocardial infarction, can evoke alterations in cardiac morphology and function. Such alterations might induce artificial early or long term effects in vivo that might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies in small animal models of heart disease. Methods: Female Wistar rats were matched for weight and distributed to sham left coronary artery ligation or untreated control. Cardiac parameters were then investigated in vivo by high-field MRI over time after the surgical procedure, determining left and right ventricular morphology and function. Additionally, the time course of several metabolic and inflammatory blood parameters was determined. Results: Rats after sham surgery showed a lower body weight for up to 8 weeks after the intervention compared to healthy controls. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw), such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05), or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05). Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in the sham operated rats compared to the controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass), but not normalized to body weight. Matching these findings, blood testing revealed prolonged metabolic and inflammatory changes after surgery not related to cardiac disease. Conclusion: There is a small distinct impact of cardio-thoracic surgical procedures on the global integrity of the organism, which in the long term also includes circumscribed repercussions on cardiac morphology and function. This impact has to be considered when analyzing data from respective studies and transferring the findings to conditions in patients.


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