bluuebunny/crossref_metadata_2025 huggingface dataset:
AN ANALYSIS OF PERSONAL FINANCIAL LITERACY AMONG ADULTS IN VHEMBE DISTRICT, A RURAL MUNICIPALITY IN SOUTH AFRICA
Authors:   University of South Africa (RSA), South Africa, Ndou Adam , Ngwenya Sam ,   University of South Africa (RSA), South Africa
Published: April 2021

Consumers in rural and low-income areas are the most financially vulnerable and are facing challenges with their finances and depend mostly on unsecured loans to finance their daily expenses. This has been exacerbated by global financial crises, which left many consumers in financial strains. The purpose of this paper is to measure the level of financial literacy focusing on the areas of day-to-day money management, financial planning, choosing appropriate financial services and products, and financial knowledge and understanding. The quantitative research approach was used to collect primary data among adults in Vhembe District Municipality (VDM), a rural and low-income municipality in South Africa. Primary data were analyzed through descriptive statistics. The results indicate that the level of financial literacy among adults in VDM is low at 38.73%. The low levels of financial literacy have serious consequences for an adult’s personal financial management skills and lead to their inability to make correct financial decisions. It is apparent that an individual’s level of financial literacy has become important in how individuals manage their finances in today’s complicated financial world. The paper concludes by suggesting interventions that could help adults to improve their level of financial literacy, manage and sustain their financial well-being.
RISKS AND EXPLOITS EXPOSED BY GDPR
Authors:   Bucharest University of Economic Studies, Romania, Stoica Liviu Adrian , Savu Robert Adrian Candoi ,   Bucharest University of Economic Studies, Romania
Published: April 2021

This paper analyzes the flaws in the GDPR rules and regulations and tries to determinate the possibilities of exploiters to use the regulations in their favor to be able to commit wrongful deeds from the different correlations between companies and customers, companies and companies. It checks the ways of how the rules are exposed to flaws and how they can be used in a malicious way while effects are analyzed as impact on the business, on the free services offered and from the reduced ability to track cyber-crime. The study is focused on the improper aspects that can come from the GDPR like restricted technology access, poor customer services, huge business costs of adapting, restrictions on privacy and innovation and cybercrimes. The study is made about the exploits exposed to companies, to customers, inside or outside the territory of Europe. It analyses the relation between customer both to company inside or outside European territory including the aspects for the collaboration between companies no matter where they are located. The study is about exposing the negative aspects of implementing the GDPR rules and regulations with all that derive from this for informing the citizens on what they need to take into consideration while trusting different service providers thinking they are protected by the law.
FACTORS INFLUENCING ONLINE PURCHASE INTENTION: A CASE OF UNIVERSITY STUDENTS IN PAKISTAN
Authors:   Institute of Business Management, Pakistan, Ahmed M. Ekhlaque , Samad Nayyer ,   The University of Northampton, United Kingdom, Khan Afshan Gul ,   Institute of Business Management, Pakistan
Published: April 2021

The paper aims to study the factors that influence online purchase intention among university students in Pakistan. A cross-sectional study was conducted between March 2020 and April 2020 to collect quantitative data on the role of six factors on online purchase intention and their degree of influence among a sample of 513 university students in Karachi with or without online shopping experience. Findings suggest that perceived benefits, shopping orientations and customer satisfaction have a significant and positive impact on purchase intention while perceived risk has a significant but negative impact. Subjective norms and e-WOM do not affect purchase intention. Results suggest that customer satisfaction is the most prominent positive influencer of online purchase intention and perceived risk is the most dominant restraining factor. The results provide a detailed insight on factors influencing online purchase intention. This is the first set of empirical data on online purchase intention among university students in Pakistan and can be used by practitioners in design and implementation of online marketing strategies in similar environments.
Means of intracellular communication: touching, kissing, fusing
Authors: Spang Anne
Published: April 2021

Eukaryotic cells are complicated factories that need ensure productivity and functionality on the cellular level as well as being able to communicate with their environment. In order to do so cells developed intracellular communication systems. For a long time, research focused mainly on the secretory/biosynthetic and endocytic routes for communication, leaving the communication with other organelles apart. In the last decade, this view has changed dramatically and a more holistic view of intracellular communication is emerging. We are still at the tip of the iceberg, but a common theme of touching, kissing, fusing is emerging as general principles of communication.
Long-run equilibrium between personal income tax and economic growth in Bulgaria
Authors:   Southwest University “Neofit Rilski”, Blagoevgrad, Bulgaria, Tanchev S.
Published: April 2021

The study analyzes the relationship of personal income tax and economic growth in the long and short runs to show which type of income tax (progressive or proportional) is more compatible with Bulgaria’s economic growth. The methods of Vector Error Correction and Correlation are applied to determine the long-run and short-run impacts of the two types of income tax. The research covers the period from the first quarter of 1999 to the first quarter of 2020. Eurostat data (85 observations) were used. The empirical research has been divided into two periods. The long-run and short-run relationships between economic growth and tax revenue from progressive income tax in Bulgaria have first been studied, followed by the relationship between economic growth and the tax revenue from proportional income tax. The research results show that there is a long-run equilibrium relationship, but not a short-run relationship, between personal income tax and economic growth. The results imply that the progressive income tax is more compatible with economic growth than proportional income tax in Bulgaria in the long run. In the short run, the progressive income tax and proportional income tax have not shown statistically significant relationships with economic growth. Therefore, a progressive income tax leads to greater economic growth than a proportional income tax. From a long-run equilibrium standpoint, it is advisable that Bulgaria switch from proportional to progressive income taxation. It may be inferred that progressive taxation is more appropriate for economic growth than proportional taxation. The results are in conformity with the theory of endogenic growth and reject the neoclassical theory.
Assessment of the effectiveness of anti-COVID tax support for innovation activities of small and medium-sized enterprises in OECD countries
Authors:   Simon Kuznets Kharkiv National University of Economics, Kharkiv, Ukraine, Shapovalova A. O. , Ivanov Yu. B. ,   Research Center for Industrial Problems of Development, National Academy of Science of Ukraine, Kharkiv, Ukraine, Tyschenko V. F. ,   Simon Kuznets Kharkiv National University of Economics, Kharkiv, Ukraine, Karpova V. V. ,   Simon Kuznets Kharkiv National University of Economics, Kharkiv, Ukraine
Published: April 2021

The global economy has rebounded from the lows of 2020, but its recovery will depend on innovations. Therefore, it is important to identify the most effective tax support instruments for the innovation activities of small and medium-sized enterprises (SMEs) that are used in the framework of anti-crisis economic policies in the OECD countries. It is suggested that tax incentives are the most effective tax instrument of all; the effectiveness of the profit tax benefit depends on the SME’s profitability; as to the social insurance and pension contribution, there is an allowable minimum of the rate, determined by the level of wages, that will stimulate innovation. To assess the effectiveness of tax support tools, the study used the methods of linear multivariate regression and simulation in Simulink. The source of information for regression analysis was the data published by the World Bank and the Organization for Economic Cooperation and Development (OECD). It was concluded that the most effective measures of tax support are tax incentives, as well as deferred payment of social insurance and pension contributions. The 10% profit tax was shown to be optimal to stimulate innovation provided the company keeps the saved profit for development. For innovative SMEs, the minimum allowable contribution rate for social insurance and pension provision, which stimulates their innovative activities, is 12%. The results of modeling confirmed that the proposed threshold indicators for supporting SMEs’ innovation activity can be an effective tool for overcoming the consequences of the global crisis caused by the COVID-19 pandemic.
Underground economy and GDP growth: Evidence from China’s tax reforms
Authors:   Guangdong Ocean University, Zhanjiang, China, Wang Yu kun , Li Zhang ,   Guangdong Ocean University, Zhanjiang, China
Published: April 2021

Since 1991, China has implemented two significant tax reforms. The first reform, in 1994, was a large-scale adjustment of the tax distribution system between the central and local governments, and the second reform, in 2012, replaced business tax with value-added tax. Also, the size of China’s underground economy decreased from 13.55% in 1995 to 12.30% in 2016. The paper presents an evaluation of the effect of the two tax reforms and the existing underground economy on GDP growth in China. GDP is defined as explained variable, the explanatory variables include: the ratio of declared income to actual income, the change of concealed income, and the influence of tax rate change on declared income and concealed income. According to the tax reform in 1994 and 2012, two dummy variables are set respectively. In methodology, this paper uses Simultaneous equations model, SUR-OLSs and Slutsky identity. Our estimation is based on the official statistics of China National Bureau of Statistics in the period from 1991 to 2019. In empirical analysis, we decomposed tax changes into tax rate effect (change of budget constraint slope) and income effect (change of tax liability), then analyzed the impact of tax elasticity on GDP growth. The empirical results demonstrate that both the 1994 tax reform and 2012 tax reform have had a positive impact on GDP, with high statistical significance respectively. The results also confirm that the increase of tax rate leads to the increase of hidden income, which eventually leads to the decrease of GDP. The offered methodology can also be applied to most countries for time series analyses.
The water footprint of beef cattle in the amazon region, Brazil
Authors: Rodrigues Junior Urandi João , Dziedzic Maurício
Published: April 2021

ABSTRACT: Food production and water scarcity, both in constant growth and intrinsically linked, are subjects of great relevance in current studies in several areas of knowledge. The impacts generated by the production of beef are at the center of major environmental debates, especially the consumption of water for the production and development of the livestock production chain. This research analyzed the use of water resources in the production of beef in the Amazon biome. The water footprint for beef cattle was of 13,074 L.kg-1 compared to a world average of 21,829 L.kg-1. Based on the data obtained it was possible to demonstrate that the presence and operationalization of this production chain in the Amazon is more efficient from the water point of view than in the other locations reported in the literature.
Agave pulquero (Agave salmiana), socio-economic and agro-ecological importance and its development perspectives: a literature review
Authors: Blas-Yañez Sandra , Thomé-Ortiz Humberto
Published: April 2021

ABSTRACT: Historically, the agave pulquero (Agave spp.) has played an important ecological, economic, social, and cultural role in Mexico. Based on a systematic exploratory review of 125 scientific documents, four areas of knowledge associated with the study of agave pulquero were identified: i) biochemistry (46,4%), ii) socioeconomics (20%), iii) cultural studies (11,2%), and iv) agroecology (22,4%). Research converges on the need to value and preserve agaves since they can play an important role in rural development actions and the life quality of future societies, depending on the diversity of food, industrial, agro-ecological and cultural uses they provide. However, there is a fragmentary construction of the research problems that prevent a comprehensive vision of the producing territories as subjects of development. It is concluded that it is necessary to generate interdisciplinary perspectives for the valorization of the agave pulquero as an asset of rural development, based on inclusive innovation strategies, adapted to the specific needs of producers and consumers.
Pressure Natriuresis in Nitric Oxide-Deficient Hypertensive Rats
Authors: FORTEPIANI LOURDES A. , RODRIGO ELENA , ORTÍZ M. CLARA , CACHOFEIRO VICTORIA , ATUCHA NOEMÍ M. , RUILOPE LUIS M. , LAHERA VICENTE , GARCÍA-ESTAN[Combining Tilde] JOAQUÍN
Published: April 2021

Chronic inhibition of nitric oxide (NO) synthesis has been shown to result in arterial hypertension and an important blunting of the pressure diuresis and natriuresis response (PDN). The mechanisms mediating these abnormalities are not completely understood. In the present study, the role of several antihypertensive drugs to ameliorate these alterations was evaluated. The PDN relationships have been evaluated in rats chronically (8 wk) treated with the NO synthesis inhibitor N
G-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg per d in the drinking water). Appropriate groups of rats were simultaneously treated with the angiotensin II receptor blocker candesartan at a low (1.5 mg/kg per d) and high (2.5 mg/kg per d) dose, with the converting enzyme inhibitor captopril (60 mg/kg per d) and with the calcium channel blocker verapamil (100 mg/kg per d). Chronic treatment with L-NAME significantly elevated mean BP (163.6 ± 6.5 mmHg versus 105.1 ± 3.6 in controls), reduced GFR and renal blood flow (RBF), and shifted to the right the PDN responses. Chronic administration of low-dose candesartan, captopril, or verapamil prevented the arterial hypertension and improved renal hemodynamics, but these levels were not completely normalized. High-dose administration also improved renal hemodynamics but induced reduced BP below the levels of control animals. Despite the normalization of the elevated BP, the PDN responses of these hypertensive treated groups were not normalized, and the slopes of the respective diuretic or natriuretic responses were very similar to those of the hypertensive untreated rats. The results indicate that interruption or blockade of the reninangiotensin system and calcium channel blockade are effective treatments for the NO-deficient arterial hypertension and renal vasoconstriction. However, the PDN responses are not normalized, and this finding suggests that the antihypertensive treatment is not enough to overcome the renal alterations associated with the chronic deficiency of NO.
Mechanism of Inhibitory Effect of Warfarin on Mesangial Cell Proliferation
Authors: YANAGITA MOTOKO , ISHII KENJI , OZAKI HARUNOBU , ARAI HIDENORI , NAKANO TORU , OHASHI KAZUMASA , MIZUNO KENSAKU , KITA TORU , DOI TOSHIO
Published: April 2021

Because proliferation of mesangial cells is a hallmark of glomerular diseases, understanding the regulatory mechanism of mesangial proliferation is important for the treatment. Warfarin has long been used to treat glomerular diseases, although its mechanism of effect on mesangial proliferation has remained unknown. Therefore, this study was conducted to examine whether warfarin can inhibit mouse mesangial cell proliferation by focusing on Gas6, which has been shown to be activated by vitamin K-dependent γ-carboxylation. In mesangial cells, Gas6 and its receptor Axl were expressed. In addition, exogenous Gas6 phosphorylated Axl, activated extracellular signal-regulated kinase, and stimulated [3H]-thymidine incorporation in mouse mesangial cells. This study also examined whether endogenous Gas6 stimulates mesangial proliferation. Conditioned medium (CM) from serum-starved mesangial cells could stimulate [3H]-thymidine incorporation and phosphorylate extracellular signal-regulated kinase, whereas CM in the presence of warfarin could not. Simultaneous administration of vitamin K could cancel the inhibitory effect of warfarin. These results suggest that vitamin K-dependent growth factors in the CM are critical for mesangial proliferation. Addition of the extracellular domain of Axl to the CM inhibited its mitogenic effect on mesangial cells, suggesting that this vitamin K-dependent growth factor is Gas6. It is concluded that Gas6 is an endogenous mitogen in mesangial cells, and warfarin inhibits mesangial proliferation possibly by inhibiting γ-carboxylation of Gas6. This study sheds light on the regulation of mesangial proliferation and may lead to a new therapeutic strategy for glomerular diseases.
Role for Interactions Between IP-10/Mig and CXCR3 in Proliferative Glomerulonephritis
Authors: ROMAGNANI PAOLA , BELTRAME CHIARA , ANNUNZIATO FRANCESCO , LASAGNI LAURA , LUCONI MICHAELA , GALLI GRAZIA , COSMI LORENZO , MAGGI ENRICO , SALVADORI MAURIZIO , PUPILLI CINZIA , SERIO MARIO
Published: April 2021

The mechanisms responsible for mesangial cell proliferation in proliferative glomerulonephritis are only partially understood. This article reports the results of an immunohistochemical study showing high expression of the chemokine receptor CXCR3 by mesangial cells of patients with IgA nephropathy, membranoproliferative glomerulonephritis, or rapidly progressive glomerulonephritis. CXCR3 was also detectable by flow cytometry in cultured human mesangial cells, in which it appeared to be functionally active, as determined by the ability of its ligand, the (interferon-γ)-inducible protein of 10 kD (IP-10) to induce intracellular Ca2+ influx. Both IP-10 and the monokine induced by interferon-γ (Mig) were also effective in inducing proliferation of human mesangial cells. These data suggest that in patients with proliferative glomerulonephritis, the chemokines IP-10 and/or Mig not only may act as chemoattractants for infiltrating mononuclear cells in the inflamed tissue, but also may directly induce the proliferation of mesangial cells.
A Mouse Model for Liddle's Syndrome
Authors: PRADERVAND SYLVAIN , WANG QING , BURNIER MICHEL , BEERMANN FRIEDRICH , HORISBERGER JEAN DANIEL , HUMMLER EDITH , ROSSIER BERNARD C.
Published: April 2021

Liddle's syndrome (or pseudoaldosteronism) is an autosomal dominant form of salt-sensitive hypertension, due to abnormal sodium transport by the renal tubule. To study the pathophysiology of salt sensitivity, a mouse model for Liddle's syndrome has been generated by Cre/loxP-mediated recombination. Under normal salt diet, mice heterozygous (L/+) and homozygous (L/L) for Liddle mutation (L) develop normally during the first 3 mo of life. In these mice, BP is not different from wild type despite evidence for increased sodium reabsorption in distal colon and low plasma aldosterone, suggesting chronic hypervolemia. Under high salt intake, the Liddle mice develop high BP, metabolic alkalosis, and hypokalemia accompanied by cardiac and renal hypertrophy. This animal model reproduces to a large extent a human form of salt-sensitive hypertension and establishes a causal relationship between dietary salt, a gene expressed in kidney and hypertension.
Early Experience with Dual Kidney Transplantation in Adults using Expanded Donor Criteria
Authors: REMUZZI GIUSEPPE , GRINYÒ JOSEP , RUGGENENTI PIERO , BEATINI MARCO , COLE EDWARD H. , MILFORD EDGAR L. , BRENNER BARRY M.
Published: April 2021

Dual transplant of marginal kidneys otherwise not considered for single transplant may give access to an expanded pool of cadaveric organs without exposing recipients to the drawbacks of a limited nephron mass supply. This prospective, case-control study compares adverse events and graft outcome in 24 recipients of two marginal kidneys from donors who were >60 yr old or who had diabetes, hypertension, or non-nephrotic proteinuria (cases), with that of 48 age- and gender-matched control subjects who received single ideal grafts at the same center and were given the same immuno-suppressive therapy. Marginal kidneys with no macroscopic abnormalities were selected for the double transplant on the basis of a predefined score of histologic damage. Six-month patient and kidney survival was 100% with both of the procedures. Incidence (20.8% versus 20.8%) and median (range) duration of posttransplant anuria (5 [2 to 12] versus 7 [2 to 13] days) were comparable in cases and control subjects, respectively. Time to normal serum creatinine and mean serum creatinine values at each time visit were comparable as well, but with significantly lower levels in cases compared with control subjects from month 2 to last follow-up (1.56 ± 0.65 versus 1.74 ± 0.73 mg/dl, P = 0.04). Diastolic BP values averaged during the entire posttransplant period were significantly lower in cases than in control subjects (83.2 ± 11.5 versus 85.1 ± 12.5 mmHg, respectively, P = 0.008). Donor/recipient body weight ratio was the only covariate significantly associated at univariate (P = 0.002) and multivariate (P = 0.001) analysis with last available serum creatinine concentrations. Incidence of acute allograft rejections (20.8% versus 18.8%) and of major surgical complications was comparable in the two groups. No renal artery or vein thrombosis was reported in either group. Dual transplants of marginal kidneys are as safe and tolerated as single transplants, and possibly offer an improved filtration power without exposing the recipient to enhanced risk of delayed renal function recovery, acute allograft rejection, or major surgical complications.
Micropuncture Analysis of Tubuloglomerular Feedback Regulation in Transgenic Mice
Authors: SCHNERMANN JURGEN
Published: April 2021

Micropuncture methods have been used widely as a means to define the function of single tubules and study the functional connection between tubules and afferent arterioles (so-called tubuloglomerular feedback [TGF]). Transgenic mouse strains have become a new research tool with the potential of shedding new light on the role of specific gene products in renal tubular and vascular function. The micropuncture approach has therefore been adapted to studies in the mouse kidney. Although the data presented here support the feasibility of using this technique in the mouse, technical improvements are desirable in the areas of anesthesia, ureteral urine collections, blood collections, volume replacement, and functional stability for extended time periods. During ketamine/inactin anesthesia, TGF responses could regularly be elicited in wild-type mice. In contrast, changes in loop flow did not alter stop-flow pressure in angiotensin II type 1A receptor and angiotensin-converting enzyme knockout mice. Infusion of angiotensin II in subpressor doses partially restored TGF responsiveness in angiotensin-converting enzyme knockout animals. Normal TGF responses compared to wild type were found in nitric oxide synthase I and thromboxane receptor knockout mice. Using free-flow micropuncture techniques, the proximal-distal single-nephron GFR difference was found to be augmented in aquaporin-1 and Na/H exchanger-3 knockout mice, suggesting TGF activation in these strains of mice. These results support an essential role of angiotensin II in TGF regulation mediated through the angiotensin II type 1A receptor. Chronic nitric oxide synthase I and thromboxane receptor deficiency did not change TGF responsiveness. Aquaporin-1 and Na/H exchanger-3 deficiency enhances TGF suppression of TGF probably by volume depletion-mediated TGF sensitization. The use of micropuncture methodology in transgenic mice combines old and new research tools in a way that promises to yield important new insights into single-nephron function in physiologic and pathophysiologic conditions.
Apical Proteins Stimulate Complement Synthesis by Cultured Human Proximal Tubular Epithelial Cells
Authors: TANG SYDNEY , SHEERIN NEIL S. , ZHOU WUDING , BROWN ZARIN , SACKS STEVEN H.
Published: April 2021

There is increasing evidence to suggest that the renal tubular epithelium is important in the pathogenesis of progressive renal failure resulting from persistent proteinuria. The role of complement in the progression of chronic renal failure is not well defined. The purpose of this study was to characterize the production of complement by human proximal tubular epithelial cells exposed to serum proteins at the apical surface. Complement C3 gene expression was analyzed by reverse transcription and PCR. C3 protein biosynthesis was confirmed by metabolic labeling followed by immunoprecipitation and quantified by enzyme-linked immunosorbent assay. In the quiescent state, proximal tubular epithelial cells grown on permeable membrane supports secreted C3 predominantly into the apical medium. The addition of 5 mg/ml serum proteins led to an 8.9-fold increase in basolateral C3 secretion and a 2.1-fold increase in apical C3 secretion, altering the ratio of basolateral: apical C3 secretion from 0.44 ± 0.16 to 1.87 ± 0.52. C3 mRNA expression was also upregulated in a time- and dose-dependent manner. Serum fractionation demonstrated that the stimulant responsible for these effects was in the molecular weight range 30 to 100 kD. The observed phenomenon was not reproduced when purified human albumin alone was used as the stimulant. These findings could provide a possible mechanism for the link between proteinuria and interstitial fibrosis. This may have potential implications for strategies directed against complement in retarding the progression of chronic renal failure.
Hypertrophy of Intramyocardial Arteriolar Smooth Muscle Cells in Experimental Renal Failure
Authors: TÖRNIG JOHANNES , GROSS MARIE-LUISE , SIMONAVICIENE AURELIA , MALL GERHARD , RITZ EBERHARD , AMANN KERSTIN
Published: April 2021

Wall thickening of intramyocardial arteries in patients with chronic renal failure may contribute to the increased susceptibility of the uremic heart to ischemic injury. In this context, the following questions arise: (1) Is intramyocardial wall thickening in experimental renal failure due to hypertrophy, hyperplasia or both? (2) Which stimuli trigger wall thickening? Using novel stereologic techniques (Nucleator, Selector), intramyocardial arteries were examined in sham-operated and subtotally nephrectomized (SNX) Sprague Dawley rats with moderate renal failure of 8 wk duration. Systolic BP during the experiment was not significantly different in both groups. Absolute and relative left ventricular weight, wall thickness (5.69 ± 1.11 μm versus 4.42 ± 0.99 μm), and wall-to-lumen ratio of intramyocardial arteries (0.117 ± 0.03 μm/μm versus 0.089 ± 0.01 μm/μm) were significantly greater in SNX than in sham-operated rats. The mean cell and nuclear volume of intramyocardial arteriolar smooth muscle cells was significantly increased in SNX rats (650 ± 230 μm3
versus 430 ± 90 μm3 and 26 ± 4.5 versus 19.9 ± 2.2 μm3, respectively). In parallel, the total arteriolar wall volume was significantly greater in the left ventricle of SNX (+ 58%) compared with sham rats. In contrast, the total length of all left ventricular arteries was comparable in both groups. The increase in mean cell volume without significant change in cell number indicates that arteriolar wall thickening in the heart of SNX rats is explained by hypertrophy rather than hyperplasia of arterial smooth muscle cells. This finding in a nonhypertensive experimental model of chronic renal failure contrasts with findings in spontaneously hypertensive rats. Independent of BP and left ventricular hypertrophy, specific growth signals must act on cardiac arteriolar smooth muscle cells.
Dietary Magnesium, Not Calcium, Regulates Renal Thiazide Receptor
Authors: FANESTIL DARRELL D. , HYDE RONALD H. , BLAKELY PATRICIA , VAUGHN DUKE A.
Published: April 2021

This study reports for the first time a relationship between dietary Mg and the renal thiazide-sensitive Na-Cl cotransporter (TZR, measured by saturation binding with 3H-metolazone). Ion-selective electrodes measured plasma ionized magnesium (PMg+ +), calcium (PCa + +), and potassium (PK +). Restricting dietary Mg for 1 wk decreased PMg + + 18%, TZR 25%, and renal excretion of magnesium (UMg) and calcium (UCa) more than 50% without changing PCa + +, PK +, or plasma aldosterone. A low Mg diet for 1 d significantly decreased PMg + +, TZR, UMg and UCa. Return of dietary Mg after 5 d of Mg restriction restored PMg + + and TZR toward normal. In the control, Mg-deficient, and Mg-repleting animals, TZR correlated with PMg + + (r = 0.86) and with UMg (r = 0.87) but not UCa (r = 0.09). Increasing oral intake of Mg for 1 wk increased PMg + + 14%, TZR 32%, UMg 74%, and UCa more than fourfold without changing PCa + + or PK +. In contrast, increasing dietary Ca content from 0.02% to 1.91% did not change TZR, but increased UCa fivefold without changing PCa + +. Hormonal mediators (if any) involved in the relationship between dietary Mg and TZR remain to be elucidated, as does the relationship between TZR and tubular reabsorption of Mg.
Regulation of Aquaporin mRNA Expression in Rat Kidney by Water Intake
Authors: MURILLO-CARRETERO MARIA I. , ILUNDÁIN ANUNCIACIÓN A. , ECHEVARRIA MIRIAM
Published: April 2021

Three aquaporins (AQP) are present in the membrane of the principal collecting duct cells. On the apical side, the levels of AQP2 protein are increased in response to both arginine vasopressin and water deprivation. However, whether this change parallels changes in the abundance of AQP3 and AQP4 in the basolateral membrane is less well known. This study evaluates the effect of either dehydration or water loading on the rat kidney mRNA expression of AQP2, AQP3, and AQP4. Poly(A+)RNA was prepared from renal cortex and medulla of control, water-deprived, well hydrated, and water-deprived rats treated with OPC31260, a V2 receptor antagonist. Northern blots were done and mRNA levels were quantified using a PhosphorImager system. Relative to control, water deprivation increased the expression of cortical AQP2, -3, and -4, whereas water loading decreased the cortical and medullar expression of AQP2, -3, and -4. Therefore, in addition to AQP2 and -3, AQP4 expression is also regulated by water intake. Treatment with OPC31260 (40 mg/kg of weight per d) inhibited up to 20 to 30% the upregulation of AQP-mRNA induced by water deprivation. Blood values of arginine vasopressin and aldosterone were significantly increased by water deprivation, whereas they were unchanged by water overloading. Taken together, these results indicate that renal AQP2, -3, and -4 expression is regulated in a coordinated manner. Simultaneous up- or downregulation of the three transcripts occurred upon either water deprivation or water loading of animals, respectively. However, the signaling mechanism for the two longterm adaptive processes may be different, and, in addition to arginine vasopressin, other factors may be involved in the transcriptional regulatory processes.
Downregulation of Neuronal Nitric Oxide Synthase in the Rat Remnant Kidney
Authors: ROCZNIAK AGNES , FRYER JAMES N. , LEVINE DAVID Z. , BURNS KEVIN D.
Published: April 2021

Chronic renal failure is associated with disturbances in nitric oxide (NO) production. This study was conducted to determine the effect of 5/6 nephrectomy (5/6 Nx) on expression of intrarenal neuronal nitric oxide synthase (nNOS) in the rat. In normal rat kidney, nNOS protein was detected in the macula densa and in the cytoplasm and nuclei of cells of the inner medullary collecting duct by both immunofluorescence and electron microscopy. Western blot analysis revealed that 2 wk after 5/6 Nx, there were significant decreases in nNOS protein expression in renal cortex (sham: 95.42 ± 15.60 versus 5/6 Nx: 47.55 ± 12.78 arbitrary units, P < 0.05, n = 4) and inner medulla (sham: 147.70 ± 26.96 versus 5/6 Nx: 36.95 ± 17.24 arbitrary units, P < 0.005, n = 8). Losartan treatment was used to determine the role of angiotensin II (AngII) AT1 receptors in the inhibition of nNOS expression in 5/6 Nx. Losartan had no effect on the decreased expression of nNOS in the inner medulla, but partially increased nNOS protein expression in the cortex of 5/6 Nx rats. In contrast, in sham rats losartan significantly inhibited nNOS protein expression in the cortex (0.66 ± 0.04-fold of sham values, P < 0.05, n = 6) and inner medulla (0.74 ± 0.12-fold of sham values, P < 0.05, n = 6). nNOS mRNA was significantly decreased in cortex and inner medulla from 5/6 Nx rats, and the effects of losartan on nNOS mRNA paralleled those observed on nNOS protein expression. These data indicate that 5/6 Nx downregulates intrarenal nNOS mRNA and protein expression. In normal rats, AngII AT1 receptors exert a tonic stimulatory effect on expression of intrarenal nNOS. These findings suggest that the reduction in intrarenal nNOS expression in 5/6 Nx may play a role in contributing to hypertension and altered tubular transport responses in chronic renal failure.
Parathyroid Hormone-Related Protein (107-139) Stimulates Interleukin-6 Expression in Human Osteoblastic Cells
Authors: DE MIGUEL FERNANDO , MARTINEZ-FERNANDEZ PILAR , GUILLEN CARLOS , VALIN ALVARO , RODRIGO ANA , MARTINEZ MARIA EUGENIA , ESBRIT PEDRO
Published: April 2021

The N-terminal region of both parathyroid hormone (PTH) and PTH-related protein (PTHrP) binds to the same PTH/PTHrP receptor in osteoblasts. However, C-terminal PTHrP (107-139) inhibits growth and various functions of osteoblasts and osteoclasts apparently through PTHrP-specific receptors. PTH (1-34) and PTHrP (1-34) rapidly induce interleukin-6 (IL-6) expression by osteoblasts. The aim of the present study was to assess the effects of PTHrP (107-139) on IL-6 gene expression and secretion by osteoblastic cells from human trabecular bone (hOB). Using reverse transcription followed by PCR, it was found that IL-6 mRNA was twofold maximally increased by either PTHrP (1-34) or PTHrP (107-139), at 10 nM, over basal within 1 to 2 h in hOB cells. This effect of PTHrP (107-139), and that of PTHrP (1-34), were abolished by the transcription inhibitor actinomycin D. Meanwhile, puromycin, a protein synthesis inhibitor, superinduced IL-6 expression in the presence or absence of each PTHrP peptide. Both PTHrP (1-34) and PTHrP (107-139), but not PTHrP (38-64), stimulated IL-6 secretion to the hOB cell-conditioned medium at 24 h, dose dependently. In addition, this maximal stimulatory effect (twofold over basal) was similar with each PTHrP peptide alone, and not additive when added together. PTHrP (107-139) stimulation of mRNA and protein in hOB cells was abolished by bisindolylmaleimide I, a protein kinase C inhibitor, but not by either adenosine 3′,5′-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS), or N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H89), two protein kinase A inhibitors. These results indicate that C-terminal PTHrP, like its N-terminal domain, induces IL-6 production by human osteoblastic cells. This effect of both PTHrP regions could provide a mechanism to modulate bone turnover.
Ambulatory Blood Pressure and Left Ventricular Mass in Normotensive Patients with Autosomal Dominant Polycystic Kidney Disease
Authors: VALERO F. ALFREDO , MARTINEZ-VEA ALBERTO , BARDAJÍ ALFREDO , GUTIERREZ CRISTINA , GARCIA CARMEN , RICHART CRISTOBAL , OLIVER JESUS A.
Published: April 2021

Higher left ventricular mass (LVM) has been found in early stages of autosomal dominant polycystic kidney disease (ADPKD). The mechanisms involved in the increase of LVM are unknown. To investigate whether LVM in ADPKD may be influenced by abnormal diurnal BP variations, the 24-h ambulatory BP profile was analyzed in a group of young normotensive ADPKD patients. Ambulatory BP monitoring and two-dimensional echocardiography were performed in 26 young normotensive ADPKD with normal renal function and in 26 healthy control subjects. LVM index was higher in ADPKD patients than in controls (90.8 ± 19.6 g/m2
versus 73.9 ± 16.1 g/m2, P = 0.001). Average 24-h and daytime systolic, diastolic, and mean BP were similar in both groups. Nighttime diastolic and mean BP, but not systolic BP, were greater in ADPKD patients. The average and percent nocturnal decrease of systolic BP was lower in ADPKD patients than in control subjects (10.0 mmHg [-3 to 24] versus 15.5 mmHg [-4 to 31], P = 0.009, and 9.0% [-2 to 22] versus 14.2% [-2 to 25], P = 0.016, respectively). On the basis of their profile BP patterns, 54% of ADPKD subjects and 31% of controls were classified as nondippers (P = 0.092). There were no differences between dippers and nondippers in left ventricular wall thickness, chamber dimensions, and mass indexes. In ADPKD patients, simple regression analysis showed that LVM index was correlated with 24-h, daytime, and nighttime systolic BP. On multiple regression analysis, the 24-h systolic BP was the only variable linked to LVM index. It is concluded that young normotensive ADPKD patients have higher LVM that is closely related to the ambulatory systolic BP. The nocturnal fall in BP is attenuated in these patients, although it is not associated with the higher LVH that they present.
Effect of Histamine H2-Receptor Antagonist on the Phosphorus-Binding Abilities of Calcium Carbonate and Calcium Lactate in Hemodialysis Patients
Authors: TAKAHASHI NORIHIRO , SHOJI TETSUO , MATSUBARA KEISUKE , HITOMI HIROFUMI , HASHIMOTO MAYUKO , KIYOMOTO HIDEYASU , UCHIDA KOICHI , MIKI SHIGEHIRO , HIROHATA MAMORU , ISHIZU TSUTOMU , AKIYAMA KENJI , MIZUSHIGE KATSUFUMI , MATSUO HIROHIDE , YUASA SHIGEKAZU
Published: April 2021

The effect of histamine H2-receptor antagonist (famotidine) on the phosphorus-binding abilities of calcium carbonate and calcium lactate were examined in 13 chronic hemodialysis patients. In seven patients receiving calcium carbonate, famotidine (20 mg/d) was given because of gastroduodenal disorders, and calcium carbonate was replaced with calcium lactate as a phosphorus binder after 4 wk of treatment with famotidine. With the 4-wk administration of famotidine accompanied by calcium carbonate, the serum phosphorus level increased from 6.3 ± 0.9 to 7.1 ± 0.5 mg/dl (P < 0.05). However, with the substitution of calcium lactate, the serum phosphorus level decreased significantly when compared to that before substitution (6.3 ± 0.2 and 6.0 ± 0.9 mg/dl after 4 and 8 wk of substitution, respectively), despite continued administration of famotidine. Serum calcium, creatinine, alkaline phosphatase, high sensitive parathyroid hormone, blood urea nitrogen, arterial blood pH, and bicarbonate were not significantly altered during the trial period. In six control patients treated with calcium carbonate alone, there were no statistical changes in serum calcium and phosphorus levels after substitution of calcium lactate for calcium carbonate. These results suggest that famotidine significantly affects the phosphorus-binding ability of calcium carbonate, but not that of calcium lactate. A careful observation of changes in the serum phosphorus level should be required in hemodialysis patients receiving calcium carbonate and histamine H2-receptor antagonists. Calcium lactate may be useful as a phosphorus binder in such hemodialysis patients.
Plasma Total Homocysteine and Hemodialysis Access Thrombosis
Authors: SHEMIN DOUGLAS , LAPANE KATE L. , BAUSSERMAN LINDA , KANAAN ELIAS , KAHN SEWELL , DWORKIN LANCE , BOSTOM ANDREW G.
Published: April 2021

Mild hyperhomocysteinemia, a putative risk factor for atherothrombotic cardiovascular disease morbidity and mortality, may contribute to the excess incidence of atherothrombotic outcomes in the dialysis-dependent end-stage renal disease population. Hemodialysis access (fistula or graft) thrombosis is an unfortunately common and costly morbidity in this patient population. In this study, using a prospective design, the potential relationship between baseline nonfasting, predialysis plasma total homocysteine (tHcy) levels and vascular access-related morbidity was examined in a cohort of 84 hemodialysis patients with a fistula or prosthetic graft as their primary hemodialysis access. Vascular access thrombotic episodes were recorded over a subsequent 18-mo follow-up period. Forty-seven patients (56% of the total) had at least one access thrombosis during the 18-mo follow-up period (median follow-up, 13 mo; rate, 0.6 events per patient-year of follow-up). Proportional hazards modeling revealed that each 1 μM/L increase in the tHcy level was associated with a 4.0% increase in the risk of access thrombosis (95% confidence interval, 1.0 to 6.0%, P = 0.008). This association persisted after adjustment for type of access (fistula versus graft), age, gender, time on dialysis, diabetes, smoking, hypertension, nutritional status, urea reduction ratio, dyslipidemia, and the presence of previous vascular disease. Elevated tHcy levels appear to confer a graded, independent increased risk for hemodialysis access thrombosis. A randomized, controlled trial examining the effect of tHcy-lowering intervention on hemodialysis access thrombosis appears to be justified.
Growth Plate Cartilage Formation and Resorption Are Differentially Depressed in Growth Retarded Uremic Rats
Authors: COBO ANGELES , LÓPEZ JOSÉ , CARBAJO EDUARDO , SANTOS FERNANDO , ALVAREZ JESÚS , FERNÁNDEZ MARTA , WERUAGA ANA
Published: April 2021

To characterize the modifications of growth plate in individuals with growth impairment secondary to chronic renal failure, young rats were made uremic by subtotal nephrectomy (NX) and, after 14 d, their tibial growth plates were studied and compared with those of sham-operated rats fed ad libitum (SAL) or pair-fed with NX (SPF). NX rats were growth retarded and severely uremic. Growth plate height (mean ± SD) was much greater (P < 0.05) in NX (868.4 ± 85.4 μm) than SAL (570.1 ± 93.5 μm) and SPF (551.9 ± 99.7 μm) rats as a result of a higher (P < 0.05) hypertrophic zone (661.0 ± 89.7 versus 362.8 ± 71.6 and 353.0 ± 93.9 μm, respectively). The increased size of the growth plate was associated with a greater number of chondrocytes and modifications in their structure, particularly in the hypertrophic zone adjacent to bone. In this zone, chondrocytes of NX animals were significantly (P < 0.05) smaller (12080.4 ± 1158.3 μm3) and shorter (34.1 ± 2.5 μm) than those of SAL (16302.8 ± 1483.4 μm3 and 37.8 ± 2.0 μm) and SPF (14465.8 ± 1521.0 μm3 and 36.3 ± 1.8 μm). The interface between the growth plate cartilage and the metaphyseal bone appeared markedly irregular in NX rats. Kinetics of chondrocytes was also modified (P < 0.05) in the NX rats, which had lower cell turnover per column per day (5.4 ± 0.9), longer duration of hypertrophic phase (89.0 ± 15.2 h), and reduced cellular advance velocity (7.4 ± 2.2 μm/h) compared with SAL (8.0 ± 1.6, 32.1 ± 6.7 h, and 11.3 ± 2.7 μm/h) and SPF (7.2 ± 1.1, 34.8 ± 5.1 h, and 10.1 ± 2.5 μ/h). Cell proliferation was no different among the three groups. Because the growth plates of SPF and SAL rats were substantially not different, modifications observed in the NX rats cannot be attributed to the nutritional deficit associated with renal failure. These findings indicate that chronic renal failure depresses both the activity of the growth plate cartilage by altering chondrocyte hypertrophy and the replacement of cartilage by bone at the metaphyseal end. The two processes are differentially depressed since cartilage resorption is more severely lowered than cartilage enlargement and this leads to an accumulation of cartilage at the hypertrophic zone.
Directed Membrane Transport Is Involved in Process Formation in Cultured Podocytes
Authors: SIMONS MATIAS , SAFFRICH RAINER , REISER JOCHEN , MUNDEL PETER
Published: April 2021

Mature glomerular visceral epithelial cells, or podocytes, are unique cells with a complex cell architecture. Characteristically, they possess a highly branched array of major processes and foot processes, which are essential for glomerular filtration in the kidney. A podocyte cell line with the potential to exhibit many features of differentiated podocytes, particularly the formation of cell processes, was recently established. In this study, it is shown that directed membrane transport is involved in process formation in cultured podocytes. The well-characterized vesicular stomatitis virus G was used as a marker protein for the biosynthetic pathway in these cells. It seems that newly synthesized vesicular stomatitis virus G is preferentially delivered into the cell processes of the podocytes, where it is colocalized with known regulators of vesicular transport from the Golgi apparatus to the plasma membrane, such as the small GTPase rab8 and the sec6/sec8 complex. To determine the role of vesicular transport in process formation, cells were treated with brefeldin A, a drug that disrupts the trafficking of post-Golgi transport vesicles. As a result, the podocytes reversibly lost their ability to form processes. These findings suggest that podocytes are dependent on a constant fresh source of lipids and proteins to form their processes.
Quantitative Trait Loci for Blood Pressure Exist Near the IGF-1, the Liddle Syndrome, the Angiotensin II-Receptor Gene and the Renin Loci in Man
Authors: NAGY ZSUZSANNA , BUSJAHN ANDREAS , BÄHRING SYLVIA , FAULHABER HANS-DIETER , GOHLKE HANS-RÜDIGER , KNOBLAUCH HANS , ROSENTHAL MAGDA , MÜLLER-MYHSOK BERTRAM , SCHUSTER HERBERT , LUFT FRIEDRICH C.
Published: April 2021

Blood pressure (BP) is heritable and finding quantitative trait loci that influence BP is an important step in identifying genes responsible for BP regulation. Sixty-six pairs of dizygotic (DZ) twin subjects and their parents were used in a sib-pair analysis to look for linkage of selected candidate genes to the quantitative trait BP. Microsatellite markers were tested in the vicinity of the gene loci for insulin-like growth factor-1 (IGF-1), Liddle syndrome, autosomal-dominant hypertension with brachydactyly, angiotensinogen, angiotensin II type 1 receptor, angiotensin-converting enzyme, renin, and lipoprotein lipase. BP was measured in a standardized manner. Heart size was determined echocardiographically. Significant linkage was found at the IGF-1, Liddle syndrome, and AT1 receptor gene for systolic BP. Linkage for diastolic BP was found at the autosomal-dominant hypertension with brachydactyly locus. Both systolic and diastolic BP were linked to the renin gene locus. The linkage was most consistent for the IGF-1 gene locus and systolic BP. Linkage was also found between the IGF-1 gene locus and posterior cardiac wall thickness, septal thickness, and left ventricular mass index. It is suggested that these quantitative trait loci may be important for the subsequent detection of allelic variants for elevated BP. Furthermore, these results linking the IGF-1 gene locus to both BP and cardiac dimensions underscore the importance of the IGF-1 gene as a candidate gene for cardiovascular disease.