Adaptive changes in GFR, tubular morphology, and transport in subtotal nephrectomized kidneys: modeling and analysis

Removal of renal mass stimulates anatomical and functional adaptations in the surviving nephrons, including elevations in single-nephron glomerular filtration rate (SNGFR) and tubular hypertrophy. A goal of this study is to assess the extent to which the concomitant increases in filtered load and tubular transport capacity preserve homeostasis of water and salt. To accomplish that goal, we developed computational models to simulate solute transport and metabolism along nephron populations in a uninephrectomized (UNX) rat and a 5/6-nephrectomized (5/6-NX) rat. Model simulations indicate that nephrectomy-induced SNGFR increase and tubular hypertrophy go a long way to normalize excretion, but alone are insufficient to fully maintain salt balance. We then identified increases in the protein density of Na+-K+-ATPase, Na+-K+-2Cl- cotransporter, Na+-Cl- cotransporter, and epithelial Na+ channel, such that the UNX and 5/6-NX models predict urine flow and urinary Na+ and K+ excretions that are similar to sham levels. The models predict that, in the UNX and 5/6-NX kidneys, fractional water and salt reabsorption is similar to sham along the initial nephron segments (i.e., from the proximal tubule to the distal convoluted tubule), with a need to further reduce Na+ reabsorption and increase K+ secretion primarily along the connecting tubules and collecting ducts to achieve balance. Additionally, the models predict that, given the substantially elevated filtered and thus transport load among each of the surviving nephrons, oxygen consumption per nephron segment in a UNX or 5/6-NX kidney increases substantially. But due to the reduced nephron population, whole animal renal oxygen consumption is lower. The efficiency of tubular Na+ transport in the UNX and 5/6-NX kidneys is predicted to be similar to sham.This research was supported by the Department of Veterans Affairs (to V. Vallon) and by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases Grants R01-DK-56248 (to V. Vallon), R01-DK-106102 (A. T. Layton and V. Vallon), and the University of Alabama at Birmingham/ University of California San Diego O'Brien Center for Acute Kidney Injury Research NIH-P30-DK-079337 (to V. Vallon). (Department of Veterans Affairs; R01-DK-56248 - National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases; R01-DK-106102 - National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases; NIH-P30-DK-079337 - University of Alabama at Birmingham/ University of California San Diego O'Brien Center for Acute Kidney Injury Research)Accepted manuscrip

Renal potassium handling in rats with subtotal nephrectomy: modeling and analysis

We sought to decipher the mechanisms underlying the kidney's response to changes in K+ load and intake, under physiological and pathophysiological conditions. To accomplish that goal, we applied a published computational model of epithelial transport along rat nephrons in a sham rat, an uninephrectomized (UNX) rat, and a 5/6-nephrectomized (5/6-NX) rat that also considers adaptations in glomerular filtration rate and tubular growth. Model simulations of an acute K+ load indicate that elevated expression levels and activities of Na+/K+-ATPase, epithelial sodium channels, large-conductance Ca2+-activated K+ channels, and renal outer medullary K+ channels, together with downregulation of sodium-chloride cotransporters (NCC), increase K+ secretion along the connecting tubule, resulting in a >6-fold increase in urinary K+ excretion in sham rats, which substantially exceeds the filtered K+ load. In the UNX and 5/6-NX models, the acute K+ load is predicted to increase K+ excretion, but at significantly reduced levels compared with sham. Acute K+ load is accompanied by natriuresis in sham rats. Model simulations suggest that the lesser natriuretic effect observed in the nephrectomized groups may be explained by impaired NCC downregulation in these kidneys. At a single-nephron level, a high K+ intake raises K+ secretion along the connecting tubule and reabsorption along the collecting duct in sham, and even more in UNX and 5/6-NX. However, the increased K+ secretion per tubule fails to sufficiently compensate for the reduction in nephron number, such that nephrectomized rats have an impaired ability to excrete an acute or chronic K+ load.This research was supported by the Department of Veterans Affairs (V. Vallon), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grants R01-DK-112042 (V. Vallon) and R01-DK-106102 (A. T. Layton and V. Vallon), and University of Alabama at Birmingham-University of California San Diego O'Brien Center for Acute Kidney Injury Research (NIDDK Grant P30-DK-079337; V. Vallon). (Department of Veterans Affairs; R01-DK-112042 - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); R01-DK-106102 - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); P30-DK-079337 - University of Alabama at Birmingham-University of California San Diego O'Brien Center for Acute Kidney Injury Research (NIDDK Grant))Accepted manuscrip

Estimation de l'épaisseur d'alluvions quaternaires dans la cuvette grenobloise par inversion des anomalies gravimétriques.

37 p.En décembre 1981 et janvier 1982 Louis Reynaud et Michel Vallon, enseignants à l'Université Scientifique et médicale de Grenoble, réalisèrent une campagne de mesures gravimétriques dans la région grenobloise . Les 149 stations établies à cette occasion sont pratiquement toutes situées sur les formations quaternaires. La carte de l'anomalie de Bouguer que l'on peut déduire de ces mesures reflète, entre autres, les variations d'épaisseur des alluvions dans la région mais ne permet pas d'estimer de manière satisfaisante ces épaisseurs. En effet seules deux stations gravimétriques localisées sur le substratum mésozoïque permettent d'estimer la valeur absolue de l'anomalie gravimétrique créée par le remplissage alluvial. Ces stations sont malheureusement trop proches l'une de l'autre (toutes deux au pied de la montagne de La Bastille) pour permettre d'estimer les gradients régionaux de l'anomalie de Bouguer. La campagne conduite de 1997 à 1999 à la demande de l'I.P.S.N. avait pour but de : a - préciser l'anomalie gravimétrique dans les zones mal couvertes par les mesures de 1981-82, en particulier au niveau de la cluse de l'Isère, au voisinage de l'Institut Laue-Langevin, région dont le paléorelief d'érosion glaciaire intéresse particulièrement l'I.P.S.N.; b - étudier la région de Biviers-Domène-Meylan-Gières où de nombreuses données de sismique réflexion permettent une estimation indépendante des épaisseurs d'alluvions ; c - couvrir largement les contreforts de la Chartreuse, du Vercors et de Belledonne afin de disposer d'une carte de l'anomalie de Bouguer "régionale" permettant d'estimer la valeur absolue de l'anomalie gravimétrique liée au remplissage quaternaire et apprécier, au mieux, la densité des formations sédimentaires mésozoïques

Remey\u27s Calming Kids with Communication

Pain management is often studied by doctors, psychologists, and child-life specialists. However, designers have a strong influence on the care, comfort and pain management of a patient, specifically one in the hospital. Pain management is a difficult topic to study and understand because everyone feels pain differently, however, by looking to the roots of pain and its affects on communication and anxiety we can learn to understand how to mollify its aches. Pediatric pain management is even more difficult to comprehend because there are many added elements involved in a painful experience

Filial Cannibalism in a Fish with Paternal Care

Filial cannibalism – the consumption of one’s own offspring – has been described in a wide range of animal taxa, while being particularly common in fish showing paternal care. Despite being a well-known phenomenon, this seemingly odd behaviour has puzzled researchers for decades and its adaptiveness is still not fully understood. Previous research on this topic has mainly focussed on the hypothesis that parents may consume their offspring to satisfy their own energetic needs, but the available evidence indicates that there is more to filial cannibalism than energetics alone. During the course of this thesis, I investigated several alternative hypotheses on the adaptiveness of filial cannibalism. For this, I conducted a series of extensive laboratory experiments using a small marine fish, the common goby (Pomatoschistus microps), as a model species. By simultaneously presenting egg-guarding male common gobies with eggs of varying age, I was able to show that the young, least valuable eggs are preferentially cannibalised (chapter I). This confirms the prediction that filial cannibalism may be a mechanisms to selectively remove and consume offspring with a certain “low-quality” phenotype. Similarly, I could demonstrate that egg infections, but not paternity, trigger such selective filial cannibalism (chapter II). Using a different approach, I tested how water salinity, egg density and their interaction relate to cannibalistic behaviour (chapter III). I could show that filial cannibalism is increased in low salinity as predicted due to increased growth of egg pathogens under such conditions, while this was not the case for the presumably similarly susceptible high-density egg clutches (chapter III). By investigating these different yet connected factors, I could demonstrate in this thesis that filial cannibalism is indeed likely influenced by a wide array of environmental, parental and offspring parameters, while highlighting egg infections as a major driver at least in fish

Reduction of Helmet Buffeting in Open Cockpit, Single Seat Race Cars

At speeds approaching 240 mph, drivers of open cockpit race cars frequently experience large aerodynamic forces which act on the helmet. These forces, specifically the aerodynamic buffeting of the helmet, reach levels which are very fatiguing and distracting to the driver, and are therefore unacceptable. Little investigation has been done in this area, because normal wind tunnel tests do not isolate the helmet from the rest of the car. During this project, measurements of aerodynamic forces acting on a helmet inside a race car cockpit were made to determine the cause of the buffeting, and to determine possible improvements. Tests showed that the sources of buffeting are turbulent separation at the rear of the helmets as well as unsteady flow in the region between helmet and headrest. Best improvements were made by preventing separation on the rear of the helmet through the introduction of a fairing, and by limiting the amount of air flow to the rear of the cockpit through modifications to the helmet and cockpit region. While the drag experienced by the helmet doubled to 2 lb through these changes, the lift was reduced from 4.8 lb to 2 lb, and the buffeting force from 5.6 oz to less than 1 oz. This represents improvements of over 60 and 80% respectively. These changes were considered to be acceptable within the regulations of the sanctioning body