A mathematical model of the rat kidney IV: whole-kidney response to hyperkalemia

2022 ◽  
Author(s):  
Alan Mark Weinstein
Keyword(s):  
Rat Kidney ◽  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Na Transport ◽  
Ample Evidence ◽  
Principal Cells ◽  
Relative Contribution ◽  
K Secretion ◽  
Luminal Flow ◽  
The Impact

The renal response to acute hyperkalemia is mediated by increased K secretion within connecting tubule (CNT), flux that is modulated by tubular effects (e.g. aldosterone) in conjunction with increased luminal flow. There is ample evidence that peritubular K blunts Na reabsorption in proximal tubule, thick ascending Henle limb, and distal convoluted tubule (DCT). While any such reduction may augment CNT delivery, the relative contribution of each is uncertain. The kidney model of this lab was recently advanced with representation of cortical labyrinth and medullary ray. Model tubules capture the impact of hyperkalemia to blunt Na reabsorption within each upstream segment. However, this forces the question of the extent to which increased Na delivery is transmitted past macula densa and its tubuloglomerular feedback (TGF) signal. Beyond increasing macula densa Na delivery, peritubular K is predicted to raise cytosolic Cl and depolarize macula densa cells, which may also activate TGF. Thus, although upstream reduction in Na transport may be larger, it appears that the DCT effect is critical to increasing CNT delivery. Beyond the flow effect, hyperkalemia reduces ammoniagenesis and reduced ammoniagenesis enhances K excretion. What this model provides is a possible mechanism. When cortical NH4 is taken up via peritubular Na,K(NH4)-ATPase, it acidifies principal cells. Consequently, reduced ammoniagenesis increases principal cell pH, thereby increasing conductance of both ENaC and ROMK, enhancing K excretion. In this model, aldosterone's effect on principal cells, diminished DCT Na reabsorption, and reduced ammoniagenesis, all provide relatively equal and additive contributions to renal K excretion.

Autoradiographic demonstration of oxytocin-binding sites in the macula densa

1989 ◽  
Vol 257 (2) ◽  
pp. F310-F314 ◽  
Author(s):  
M. E. Stoeckel ◽  
M. J. Freund-Mercier
Keyword(s):  
Binding Sites ◽  
Cellular Localization ◽  
Rat Kidney ◽  
Juxtaglomerular Apparatus ◽  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Binding Characteristics ◽  
Conventional Film ◽  
High Concentrations ◽  
Autoradiographic Technique

Specific oxytocin (OT)-binding sites were localized in the rat kidney with use of a selective 125I-labeled OT antagonist (125I-OTA). High concentrations of OT binding sites were detected on the juxtaglomerular apparatus with use of the conventional film autoradiographic technique. No labeling occurred on other renal structures. The cellular localization of the OT binding sites within the juxtaglomerular apparatus was studied in light microscope autoradiography, on semithin sections from paraformaldehyde-fixed kidney slices incubated in the presence of 125I-OTA. These preparations revealed selective labeling of the macula densa, mainly concentrated at the basal pole of the cells. Control experiments showed first that 125I-OTA binding characteristics were not noticeably altered by prior paraformaldehyde fixation of the kidneys and second that autoradiographic detection of the binding sites was not impaired by histological treatments following binding procedures. In view of the role of the macula densa in the tubuloglomerular feedback, the putative OT receptors of this structure might mediate the stimulatory effect of OT on glomerular filtration.

A region-based mathematical model of the urine concentrating mechanism in the rat outer medulla. I. Formulation and base-case results

2005 ◽  
Vol 289 (6) ◽  
pp. F1346-F1366 ◽  
Author(s):  
Anita T. Layton ◽  
Harold E. Layton
Keyword(s):  
Mathematical Model ◽  
Rat Kidney ◽  
Tubuloglomerular Feedback ◽  
Transepithelial Transport ◽  
Base Case ◽  
Model Parameters ◽  
Outer Medulla ◽  
Concentrating Mechanism ◽  
The Impact ◽  
Urine Concentrating Mechanism

We have developed a highly detailed mathematical model for the urine concentrating mechanism (UCM) of the rat kidney outer medulla (OM). The model simulates preferential interactions among tubules and vessels by representing four concentric regions that are centered on a vascular bundle; tubules and vessels, or fractions thereof, are assigned to anatomically appropriate regions. Model parameters, which are based on the experimental literature, include transepithelial transport properties of short descending limbs inferred from immunohistochemical localization studies. The model equations, which are based on conservation of solutes and water and on standard expressions for transmural transport, were solved to steady state. Model simulations predict significantly differing interstitial NaCl and urea concentrations in adjoining regions. Active NaCl transport from thick ascending limbs (TALs), at rates inferred from the physiological literature, resulted in model osmolality profiles along the OM that are consistent with tissue slice experiments. TAL luminal NaCl concentrations at the corticomedullary boundary are consistent with tubuloglomerular feedback function. The model exhibited solute exchange, cycling, and sequestration patterns (in tubules, vessels, and regions) that are generally consistent with predictions in the physiological literature, including significant urea addition from long ascending vasa recta to inner-stripe short descending limbs. In a companion study (Layton AT and Layton HE. Am J Physiol Renal Physiol 289: F1367–F1381, 2005), the impact of model assumptions, medullary anatomy, and tubular segmentation on the UCM was investigated by means of extensive parameter studies.

Ultrastructural localization of Na-K-2Cl cotransporter in thick ascending limb and macula densa of rat kidney

1998 ◽  
Vol 275 (6) ◽  
pp. F885-F893 ◽  
Author(s):  
Søren Nielsen ◽  
Arvid B. Maunsbach ◽  
Carolyn A. Ecelbarger ◽  
Mark A. Knepper
Keyword(s):  
Plasma Membrane ◽  
Rat Kidney ◽  
Ultrastructural Localization ◽  
Macula Densa ◽  
Tubuloglomerular Feedback ◽  
Kidney Cortex ◽  
Apical Plasma Membrane ◽  
Thick Ascending Limb ◽  
Rat Kidney Cortex ◽  
Intracellular Vesicles

A bumetanide-sensitive Na-K-2Cl cotransporter, BSC-1, is believed to mediate the apical component of transcellular NaCl absorption in the thick ascending limb (TAL) of Henle’s loop. To study its ultrastructural localization in kidney, we used an affinity-purified, peptide-derived polyclonal antibody against rat BSC-1. Immunoblots from rat kidney cortex and outer medulla revealed a solitary 161-kDa band in membrane fractions. Immunocytochemistry of 1-μm cryosections demonstrated strong BSC-1 labeling of the apical and subapical regions of medullary and cortical TAL cells. Notably, macula densa cells also exhibited distinct labeling. Distal convoluted tubules and other renal tubule segments were unlabeled. Immunoelectron microscopy demonstrated that BSC-1 labeling was associated with the apical plasma membrane and with subapical intracellular vesicles in medullary and cortical TAL and in macula densa cells. Smooth-surfaced TAL cells, in particular, had extensive BSC-1 labeling of intracellular vesicles. These results support the view that BSC-1 provides the apical pathway for NaCl transport across the TAL and that an extensive intracellular reservoir of BSC-1 is present in a subpopulation of TAL cells. Furthermore, the BSC-1 localization in the apical plasma membrane of macula densa cells is consistent with its proposed role in tubuloglomerular feedback.

scholarly journals The impact of the Nutri-Score front-of-pack nutrition label on purchasing intentions of unprocessed and processed foods: post-hoc analyses from three randomized controlled trials

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Manon Egnell ◽  
Pilar Galan ◽  
Morgane Fialon ◽  
Mathilde Touvier ◽  
Sandrine Péneau ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Low Income ◽  
P Value ◽  
Controlled Trials ◽  
Nutrition Label ◽  
Randomized Controlled ◽  
Food Purchases ◽  
Relative Contribution ◽  
Processed Products ◽  
The Impact

Abstract Background The Nutri-Score summary graded front-of-pack nutrition label has been identified as an efficient tool to increase the nutritional quality of pre-packed food purchases. However, no study has been conducted to investigate the effect of the Nutri-Score on the shopping cart composition, considering the type of foods. The present paper aims to investigate the effect of the Nutri-Score on the type of food purchases, in terms of the relative contribution of unpacked and pre-packed foods, or the processing degree of foods. Methods Between September 2016 and April 2017, three consecutive randomized controlled trials were conducted in three specific populations – students (N = 1866), low-income individuals (N = 336) and subjects suffering from cardiometabolic diseases (N = 1180) – to investigate the effect of the Nutri-Score on purchasing intentions compared to the Reference Intakes and no label. Using these combined data, the proportion of unpacked products in the shopping carts, as well as the distribution of products across food categories taking into account the degree of processing (NOVA classification) were assessed by trials arm. Results The shopping carts of participants simulating purchases with the Nutri-Score affixed on pre-packed foods contained higher proportion of unpacked products – especially raw fruits and meats, i.e. with no FoPL –, compared to participants purchasing with no label (difference of 5.93 percentage points [3.88–7.99], p-value< 0.0001) or with the Reference Intakes (difference of 5.27[3.25–7.29], p-value< 0.0001). This higher proportion was partly explained by fewer purchases of pre-packed processed and ultra-processed products overall in the Nutri-Score group. Conclusions These findings provide new insights on the positive effect of the Nutri-Score, which appears to decrease purchases in processed products resulting in higher proportions of unprocessed and unpacked foods, in line with public health recommendations.

scholarly journals Single entity electrochemistry and the electron transfer kinetics of hydrazine oxidation

Nano Research ◽  
2021 ◽  
Author(s):  
Ruiyang Miao ◽  
Lidong Shao ◽  
Richard G. Compton
Keyword(s):  
Electron Transfer ◽  
Bulk Solution ◽  
Relative Contribution ◽  
Rate Determining Step ◽  
Multistep Process ◽  
Ph Range ◽  
Electro Catalytic Oxidation ◽  
Single Particle Impact ◽  
The Impact ◽  
Kinetics Of

AbstractThe mechanism and kinetics of the electro-catalytic oxidation of hydrazine by graphene oxide platelets randomly decorated with palladium nanoparticles are deduced using single particle impact electrochemical measurements in buffered aqueous solutions across the pH range 2–11. Both hydrazine, N2H4, and protonated hydrazine N2H5+ are shown to be electroactive following Butler-Volmer kinetics, of which the relative contribution is strongly pH-dependent. The negligible interconversion between N2H4 and N2H5+ due to the sufficiently short timescale of the impact voltammetry, allows the analysis of the two electron transfer rates from impact signals thus reflecting the composition of the bulk solution at the pH in question. In this way the rate determining step in the oxidation of each specie is deduced to be a one electron step in which no protons are released and so likely corresponds to the initial formation of a very short-lived radical cation either in solution or adsorbed on the platelet. Overall the work establishes a generic method for the elucidation of the rate determining electron transfer in a multistep process free from any complexity imposed by preceding or following chemical reactions which occur on the timescale of conventional voltammetry.

Abnormal Spinal Cord Myelination due to Oligodendrocyte Dysfunction in a Model of Huntington’s Disease

2021 ◽  
pp. 1-8
Author(s):  
Costanza Ferrari Bardile ◽  
Harwin Sidik ◽  
Reynard Quek ◽  
Nur Amirah Binte Mohammad Yusof ◽  
Marta Garcia-Miralles ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Oligodendrocyte Progenitor Cells ◽  
Wild Type ◽  
Specific Expression ◽  
Relative Contribution ◽  
Related Proteins ◽  
The Impact ◽  
Cervical Area

Background: The relative contribution of grey matter (GM) and white matter (WM) degeneration to the progressive brain atrophy in Huntington’s disease (HD) has been well studied. The pathology of the spinal cord in HD is comparatively less well documented. Objective: We aim to characterize spinal cord WM abnormalities in a mouse model of HD and evaluate whether selective removal of mutant huntingtin (mHTT) from oligodendroglia rescues these deficits. Methods: Histological assessments were used to determine the area of GM and WM in the spinal cord of 12-month-old BACHD mice, while electron microscopy was used to analyze myelin fibers in the cervical area of the spinal cord. To investigate the impact of inactivation of mHTT in oligodendroglia on these measures, we used the previously described BACHDxNG2Cre mouse line where mHTT is specifically reduced in oligodendrocyte progenitor cells. Results: We show that spinal GM and WM areas are significantly atrophied in HD mice compared to wild-type controls. We further demonstrate that specific reduction of mHTT in oligodendroglial cells rescues the atrophy of spinal cord WM, but not GM, observed in HD mice. Inactivation of mHTT in oligodendroglia had no effect on the density of oligodendroglial cells but enhanced the expression of myelin-related proteins in the spinal cord. Conclusion: Our findings demonstrate that the myelination abnormalities observed in brain WM structures in HD extend to the spinal cord and suggest that specific expression of mHTT in oligodendrocytes contributes to such abnormalities.

pHi determines rate of sodium transport in frog skin: results of a new method to determine pHi

1994 ◽  
Vol 266 (3) ◽  
pp. F367-F374 ◽  
Author(s):  
R. Rick
Keyword(s):  
Frog Skin ◽  
Nuclear Potential ◽  
Na Channel ◽  
Cytoplasmic Ph ◽  
Na Transport ◽  
Principal Cells ◽  
Weak Organic Acid ◽  
Transepithelial Na Transport ◽  
Cell Layers ◽  
Important Regulator

The pH of the isolated frog skin epithelium was determined on a cellular and subcellular level based on the distribution of a weak organic acid, 4-bromobenzoic acid. The indicator is detectable by X-ray microanalysis due to the presence of an element label. The results show that the pH of principal cells, but not the Na concentration, is closely correlated with the rate of transepithelial Na transport. Acidification leads to an inhibition of Na transport, regardless of whether the change was spontaneous or experimentally induced. Under the conditions of this study, the pH of principal cells was not well regulated. At a bath pH of 7.0, large pH differences between the cell layers were detectable. In mitochondria-rich cells, the pH was a function of the intracellular Cl concentration but not the Na transport rate. The cytoplasmic pH consistently exceeded the nuclear pH. The nuclear-cytoplasmic pH differential in principal cells amounted to 0.3 pH units, which is equivalent to a nuclear potential of -17 mV. The results support the view that the intracellular pH (pHi) is an important regulator of transepithelial Na transport. Regulation is primarily achieved at the level of the apical Na channel, making the Na influx the rate-limiting step in Na reabsorption.

The Relevance of Personal Domain Satisfaction for the Quality of Life in South Africa

1988 ◽  
Vol 18 (3) ◽  
pp. 69-75 ◽  
Author(s):  
Valerie Møller
Keyword(s):  
Quality Of Life ◽  
South African ◽  
Well Being ◽  
Positive Influence ◽  
Subjective Well Being ◽  
South Africans ◽  
Relative Contribution ◽  
Personal Domain ◽  
The Impact

South African psychologists have identified the improvement of quality of life as a major goal of the 1980s. This paper reviews the impact of satisfaction with personal aspects of life on perceived well-being. The results of an exploratory study of South African quality of life conducted among 5 587 individuals of all population groups are discussed. Findings confirm the salience of the personal domain and the positive influence of personal satisfactions on subjective well-being. However, results of regression analyses suggest that the relative contribution of satisfactions in the personal domain is too low to play a major role in improving the quality of life of all South Africans in the longer term.

scholarly journals Increased intracellular pH at the macula densa activates nNOS during tubuloglomerular feedback

2005 ◽  
Vol 67 (5) ◽  
pp. 1837-1843 ◽  
Author(s):  
Ruisheng Liu ◽  
Oscar A. Carretero ◽  
Yilin Ren ◽  
Jeffrey L. Garvin
Keyword(s):  
Intracellular Ph ◽  
Macula Densa ◽  
Tubuloglomerular Feedback

Stimulation of melanin synthesis in melanoma cells by cold plasma

2018 ◽  
Vol 400 (1) ◽  
pp. 101-109 ◽  
Author(s):  
Sybille Hasse ◽  
Marie-Christine Müller ◽  
Karin Uta Schallreuter ◽  
Thomas von Woedtke
Keyword(s):  
Transcription Factor ◽  
Cell Lines ◽  
Skin Color ◽  
Reactive Nitrogen Species ◽  
Cold Plasma ◽  
Biological Effects ◽  
Ample Evidence ◽  
Melanin Biosynthesis ◽  
Melanin Contents ◽  
The Impact

Abstract Skin color is derived from epidermal melanocytes that contain specialized organelles in which melanin is formed. The formation of melanin is a well-orchestrated process, and reactive oxygen species (ROS) play a role in numerous enzymatic conversions, such as the reactions catalyzed by tyrosinase and tyrosine hydroxylase. Currently, there is ample evidence that cold plasma exerts biological effects on cells through the impact of ROS and reactive nitrogen species (RNS). Modulation of melanin biosynthesis by cold plasma has not yet been investigated. This study investigated melanin biosynthesis of human melanoma cell lines with different endogenous melanin contents (SK-Mel 28, G-361, FM-55-P and MNT-1) in response to cold plasma-derived reactive species. Initially, the distribution of melanosomes, via immunofluorescence, and the influence of microphthalmia-associated transcription factor (MiTF), as a key transcription factor, was investigated. In our experimental setup, all of the tested cell lines had an elevated melanin content after exposure to cold plasma. These promising results suggest a novel potential application of cold plasma for the regulation of melanogenesis and may be a useful tool for influencing skin color in the future.

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