bluuebunny/crossref_metadata_2025 huggingface dataset:
Technology Acceptance Model Perilaku Pengguna pada Sistem Enterprise Dompet Dhuafa
Authors: Khumaidi Imam Ali , Kusumaningtyas Rinda Hesti
Published: April 2021

Dompet Dhuafa Enterprise System (DESI) is a system created in 2015. Initially it was created to replace the Fundrising Administration System (SANDRA) because SANDRA is a desktop-based application. Nowadays DESI is only used for budgeting functions and “Tebar Hewan Kurban” (THK) its a sacrificial animal stocking functions. DESI which has daily functions such as budgeting and seasonal functions in THK. In its implementation, DESI which is a web-based system sometimes becomes difficult to access when the system has a problem. This certainly makes the budgeting function that is used in daily activities become not implemented. THK's function in DESI was also inseparable from problems, one of which was the presence of volunteers who did not directly enter the data of prospective victims into DESI during the THK implementation. New data entered into DESI on the first Tasyrik day, for example, will increase work in other divisions. It would be different if it had been done before the sacrificial feast. This study aims to determine the factors that influence the acceptance behavior of DESI users. In this quantitative study using the Technology Acceptance Model (TAM) model. Sampling in this study using purposive sampling and accidental sampling. This study uses PLS-SEM for data processing and uses the application of SmartPLS version 3. There are 6 variables examined in this study, namely perceived usefulness, perceived easy of use, format, attitude using, behavioral intention to use, and actual system usage. From 7 hypotheses proposed there is one hypothesis that is rejected, namely the path attitude toward using the behavioral intention to use.
Pengaruh Bimbingan Konseling dan Pembelajaran Akidah Akhlak Terhadap Perilaku Keberagamaan Siswa di Mts Ma’had Al-Zaytun Indramayu
Authors: Humaeroh Iis
Published: April 2021

Class IX will soon graduate and continue to higher education. For this reason, scientific provisions in learning morals and counseling are needed to prepare graduates who are smart and have good morals. This study was to determine the effect of counseling guidance and learning akidah akhlak on students' religious behavior in MTs. Ma'had Al-Zaytun Indramayu. The object of this research is the students of class IX MTs Ma'had Al-Zaytun Indramayu. This research was conducted on 135 respondents using a quantitative descriptive approach. Methods of data collection using survey methods, with the research instrument is a questionnaire. The approach used in this research is SPSS. This study proves that counseling guidance has a positive and significant effect on students 'religious behavior, which means that counseling plays a role in improving students' religious behavior. Learning akidah akhlak also has a positive and significant effect on students 'religious behavior, which can be interpreted that learning akidah akhlak plays a role in improving students' religious behavior. So, counseling and learning of akidah akhlak together have a positive and significant effect on students' religious behavior.Keywords: Counseling Guidance, Learning Akidah Akhlak, Students' Religious Behavior ABSTRAKKelas IX akan segera lulus dan melanjutkan ke jenjang pendidikan yang lebih tinggi. Untuk itu bekal keilmuan dalam pembelajaran akidah akhlak dan bimbingan konseling sangat diperlukan untuk menyiapkan lulusan yang cerdas dan berakhlakul karimah. Penelitian ini untuk mengetahui pengaruh bimbingan konseling dan pembelajaran akidah akhlak terhadap perilaku keberagamaan siswa di MTs. Ma’had Al-Zaytun Indramayu. Objek penelitian ini adalah siswa kelas IX MTs. Ma’had Al-Zaytun Indramayu. Penelitian ini dilakukan terhadap 135 responden dengan menggunakan pendekatan deskriptif kuantitatif. Metode pengumpulan data menggunakan metode survey, dengan instrument penelitian adalah kuesioner. Pendekatan yang digunakan dalam penelitian ini adalah SPSS. Penelitian ini membuktikan bahwa bimbingan konseling berpengaruh positif dan signifikan terhadap perilaku keberagamaan siswa, yang mana dapat diartikan bahwa bimbingan konseling berperan dalam meningkatkan perilaku keberagamaan siswa. Pembelajaran akidah akhlak juga berpengaruh positif dan signifikan terhadap perilaku keberagamaan siswa, yang mana dapat diartikan bahwa Pembelajaran akidah akhlak berperan dalam meningkatkan perilaku keberagamaan siswa. Jadi, bimbingan konseling dan pembelajaran akidah akhlak secara bersama-sama berpengaruh positif dan signifikan terhadap perilaku keberagamaan siswa.Kata Kunci: Bimbingan Konseling, Pembelajaran Akidah Akhlak, Perilaku Keberagamaan Siswa
Dry biocleaning of artwork: an innovative methodology for Cultural Heritage recovery?
Authors: Ranalli Giancarlo , Bosch-Roig Pilar , Crudele Simone , Rampazzi Laura , Corti Cristina , Zanardini Elisabetta
Published: April 2021

An innovative methodology is proposed, based on applied biotechnology to the recovery of altered stonework: the “dry biocleaning“, which envisages the use of dehydrated microbial cells without the use of free water or gel-based matrices. This methodology can be particularly useful for the recovery of highly-ornamented stoneworks, which cannot be treated using the conventional cleaning techniques. The experimental plan included initial laboratory tests on Carrara marble samples, inoculated with dehydrated Saccharomyces cerevisiae yeast cells, followed by on-site tests performed on “Quattro Fontane” (The Four Fountains), a travertine monumental complex in Rome (Italy), on altered highly ornamented areas of about 1,000 cm2. The mechanism is based on the spontaneous re-hydration process due to the environmental humidity and on the metabolic fermentative activity of the yeast cells. Evaluation by physical-chemical analyses, after 18 hours of the biocleaning, confirmed a better removal of salts and pollutants, compared to both nebulization treatment and control tests (without cells). The new proposed on-site dry biocleaning technique, adopting viable yeast cells, represents a promising method that can be further investigated and optimized for recovering specific altered Cultural Heritage stoneworks.
Fios de memórias... Sobre possibilidades de escritas de si e invenção de mundos...
Authors: Ferraço Carlos Eduardo
Published: April 2021

RESUMO Trata-se de artigo que tem como objetivo problematizar diferentes acontecimentos vividos na imanência de uma vida, a partir de alguns fios de memórias assumidos como possibilidades de escritas de produção de si e de invenção de mundos. Nesse sentido, busca escapar, das representações e das explicações que se insinuam como atestados de verdade do vivido, aliados à hipertrofia do Eu, marcas do capítulo da Modernidade que celebra o surgimento de um sujeito autocentrado e dotado de uma consciência plena. Para tanto, busca enredar diferentes temporalidades que se constituíram como processos de autoformação, em meio a epistemologias e experimentações de vida, assumidas como dobras que nos permitiram evidenciar questões afetas às rupturas e às descontinuidades, de modo a nos ajudar a defender que uma vida está sempre em excesso em relação a qualquer escrita que se faça sobre ela. Se, ao final da leitura, surgir um fio de Ariadne que se mostre como um enredo preestabelecido por nós trata-se, certamente, de um efeito que reverberou com o próprio ato da escrita e não como efeito de uma intenção-causa primeira. Se me perguntarem: Houve esse memorial ou você inventou? Eu diria: Se não houve, agora, porque escrevi, passou a existir. Ele nunca aconteceu como verdade a priori para que possa insurgir como invenção, quantas vezes forem necessárias.
A ambição de ser o desejo do outro: escritas mestiças de uma família do subúrbio do Rio de Janeiro
Authors: Castro Andreia Alves Monteiro de , Alves Luciana Pires
Published: April 2021

RESUMO O presente artigo procura interpelar as narrativas da experiência mestiça não só como produção de branqueamento, mas também como encenação de um estereótipo. Ambos encarnados na vivência da nossa família, refletindo tensões, modos e projetos de identidade nacional. A romantização da mestiçagem, lugar de produção, de fundação e de disseminação do desejo sempre insatisfeito de ser outro, marca o jogo de projeções, simulações e dissimulações da narrativa de nossa ascendência. Enquanto pesquisadoras, buscamos desvendar alguns mistérios, preencher lacunas, analisar as tensões dessas histórias que nem sempre contavam os fatos pelo que era falado, mas pelo interdito, não dito, mal dito. Conhecer o processo de formação e de conformação das famílias, muitas das vezes, no leva a conhecer o processo de formação e de conformação da sociedade, do país e do mundo.
Memória, identidade e docência: recordações-referência de professores iniciantes na educação superior
Authors: Soares Sebastião Silva , Guimarães Selva
Published: April 2021

RESUMO Este trabalho objetiva analisar recordações-referência de três professores em início de carreira na educação superior, por meio da pesquisa (auto)biográfica. Para tanto, empregou-se uma entrevista narrativa com questionamentos sobre a história de vida, a formação escolar, o percurso acadêmico e o desenvolvimento profissional. Os aspectos salientados por eles no estudo demonstraram elementos significativos na escolha pela profissão e a constituição da aprendizagem docente. Diante das recordações-referência, evidenciou-se que as marcas e imagens da docência advêm de um repertório da própria história de vida desses sujeitos. Tais reminiscências são carregadas de sentimentos positivos e alegres configurados pela influência familiar na referida escolha, por trajetórias com os antigos mestres, além das brincadeiras e dos processos de inserção/iniciação à docência na universidade. A aprendizagem nessa área não aconteceu de maneira neutralizada, mas sim tecida pelos percursos formativos vividos pelos professores em suas histórias de vida e pelos caminhos profissionais na manutenção ou superação de crenças e valores sobre a profissão docente. Ademais, visualizaram-se as subjetividades que permeiam a construção da identidade dos docentes, ou seja, como se constituíram na profissão e nos diversos contextos históricos de formação.
“Como eu vou fazer pesquisa sozinha?” O processo de inserção na pós-graduação evidenciado nas narrativas de uma professora
Authors: Starling Cláudia , Conti Keli Cristina , Nunes Célia
Published: April 2021

RESUMO Este trabalho é fruto de uma investigação que objetiva compreender os processos de inserção de professores no magistério superior em universidades federais, em uma perspectiva longitudinal. Neste artigo, de natureza (auto) biográfica, analisamos os processos de inserção de uma professora, a partir de suas narrativas, durante os primeiros anos de exercício da profissão, de 2016 a 2020. O olhar interpretativo desses relatos recai para como, em cada narrativa escrita, as experiências vividas vão sendo rememoradas, em um “ir e vir” da temporalidade. Enfatizamos a reflexão sobre a inserção na docência e na pós-graduação, especificamente nas atividades de pesquisa e orientação. Os resultados evidenciaram tensões em relação à complexidade do exercício profissional no contexto universitário. A história (re)contada do período de transição no estágio probatório traz elementos que marcam o processo de constituição identitária docente, e reforça a percepção sobre como os processos interativos são propulsores de novas possibilidades de atuação e inserção dos docentes na pós-graduação.
Aprendizagens do “tornar-se”, das experiências formadoras e da visibilidade: aproximações entre autobiografias e educação
Authors: Lira André Augusto Diniz , Passeggi Maria da Conceição
Published: April 2021

RESUMO Ainda que a educação seja um empreendimento coletivo, histórico e circunstanciado, a dinâmica do sujeito da aprendizagem é perpassada por sua existencialidade e por sua singularidade. Nosso objetivo, neste artigo, é analisar aprendizagens biográficas significativas na construção do tornar-se escritor, nas autobiografias literárias de Manuel Bandeira (1886-1968), Lêdo Ivo (1924-2012) e Ferreira Gullar (1930-2016). O critério de variabilidade foi decisivo para a escolha desses autores, posto que suas obras são marcadas por diferentes gerações e escolas literárias. Nosso olhar tem como base abordagens (auto)biográficas em educação, que interrogam a experiência da formação na temporalidade do sujeito, partindo de um enfoque epistemológico no qual a subjetividade é crucial. Para tanto, consideramos, inicialmente, a discussão entre autobiografia e educação; posteriormente, avaliamos como as aprendizagens biográficas se apresentam nas trajetórias dos autores estudados. Os resultados das análises consideram três dinâmicas de aprendizagem em suas vidas: a) tornar-se si mesmo; b) as experiências formadoras constitutivas da escrita autobiográfica; c) a visibilidade ética e estética do mundo. Concluímos discutindo a importância dessas aprendizagens na proposição de uma educação para a singularidade que recupere esses elementos da aprendizagem biográfica de forma dinâmica e agregadora.
Conquistar seu tempo através da formação dos ritmos da própria vida
Authors: Pineau Gaston , Breton Hervé
Published: April 2021

RESUMO Se as pesquisas de Gaston Pineau sobre histórias de vida em formação são reconhecidas na Europa e amplamente divulgadas no Brasil, como em outros lugares do mundo, aquelas sobre a relação entre temporalidades e processos de formação são igualmente importantes. O objetivo desta entrevista é apresentar, utilizando uma abordagem genealógica, as etapas pelas quais este trabalho sobre o tempo foi sendo constituído ao longo da pesquisa de Gaston Pineau e, em seguida, examinar as dimensões contributivas destes trabalhos sobre os modos de formação das correntes de auto-formação, formação por alternância, formação experiencial e abordagens narrativas e antropoformativas.
Apresentação - Narrativas biográficas, temporalidades e hermenêutica do sujeito
Authors: Cunha Maria Amália de A. , Breton Hervé
Published: April 2021

RESUMO Narrar uma experiência envolve organizá-la temporalmente, encontrar as palavras para serem ditas e configurar os momentos e os períodos da vida em uma história. Assim, para que os processos de compreensão e autoformação aconteçam, a experiência deve se tornar dizível para, em seguida, construir uma unidade histórica que pareça verdadeira e completa do ponto de vista do narrador. Neste sentido, as dimensões temporais parecem determinantes sobre os efeitos formativos da narração: duração das experiências vividas a partir das quais se desenrola a narração biográfica; tempo disponível para compor um relato, escrevê-lo e socializá-lo; distância temporal do vivido ao momento de sua narração, entre outras. O objetivo deste dossiê é, portanto, analisar os tensionamentos que envolvem a dinâmica das temporalidades da narrativa, seus efeitos e os processos de compreensão que dela resultam.
Avaliação do risco de sangramento na profilaxia do tromboembolismo venoso
Authors: Chindamo Maria Chiara , Marques Marcos Arêas
Published: April 2021

Resumo O tromboembolismo venoso (TEV) é uma das principais causas preveníveis de morbimortalidade em pacientes hospitalizados, sendo a embolia pulmonar (EP) fatal possivelmente a sua primeira manifestação. Diretrizes nacionais e internacionais recomendam o uso de modelos de avaliação de risco para a prescrição de profilaxia do TEV em pacientes hospitalizados. Apesar das evidências e diretrizes de apoio, o uso da tromboprofilaxia permanece abaixo do ideal, o que pode resultar da baixa conscientização dos benefícios da profilaxia, mas também pode refletir o medo de complicações hemorrágicas, justificando a subutilização da tromboprofilaxia em todo o mundo. A avaliação do risco de sangramento é, portanto, necessária para a adequação de profilaxia e deve ser realizada de forma concomitante à avaliação do risco de trombose. O objetivo desta revisão é salientar a importância da avaliação conjunta do risco de TEV e do risco de sangramento em pacientes hospitalizados.
The impact of exercise training on calf pump function, muscle strength, ankle range of motion, and health-related quality of life in patients with chronic venous insufficiency at different stages of severity: a systematic review
Authors: Silva Keity Lamary Souza , Figueiredo Eduardo Augusto Barbosa , Lopes Cíntia Pimenta , Vianna Marcus Vinicius Accetta , Lima Vanessa Pereira , Figueiredo Pedro Henrique Scheidt , Costa Henrique Silveira
Published: April 2021

Abstract Exercise training (ET) is an important tool in the management of patients with chronic venous insufficiency (CVI). The objective of this article was to discuss the effects of ET on the calf pump, functional parameters, and quality of life of patients with mild and advanced CVI. A systematic review was conducted and eleven studies were included. In patients with mild CVI, ET was effective for improving venous reflux, muscle strength, ankle range of motion, and quality of life. In advanced CVI patients, ET increased ejection fraction, reduced residual volume fraction, and improved muscle strength and ankle range of motion, but did not change venous reflux indices or quality of life. It is concluded that ET is effective for improving calf pump function, muscle strength, and ankle range of motion in CVI. In patients with mild CVI, additional benefits were observed in quality of life.
Improvement of semen parameters after coil embolization of varicoceles: a systematic review
Authors: Belczak Sergio Quilici , Stefaniak Vanessa , Góes Leonardo Garcia , Coelho Neto Felipe , Araújo Walter Jr. Boim de , Silva Nathalia Almeida Cardoso da
Published: April 2021

Abstract This systematic review was conducted in accordance with the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, including clinical studies in which one of the outcomes was semen parameter improvement after varicocele embolization using coils only. The objective of the review was to assess the evidence on the role of embolization using coils alone for semen parameter improvement in men with varicocele, since embolization using coils is the most cost-effective method of varicocele repair. Study quality was assessed using the methodological index for non-randomized studies (MINORS). Out of six retrospective and two prospective observational or comparative clinical studies involving 701 patients, semen concentration improved significantly in all five studies that assessed this parameter. Mean semen motility improved significantly in seven studies. The impact of embolization on semen density could not be analyzed.
Resultados do tratamento do refluxo de veias safenas com endolaser 1.470 nm e correlação com o grau de insuficiência venosa
Authors: Silva Ana Paula Pires , Pinto Daniel Mendes , Milagres Vanessa Aline Miranda Vieira , Bez Leonardo Ghizoni , Maciel Júlio César Arantes , Lopes Caetano de Souza
Published: April 2021

Resumo Contexto Pacientes com doença venosa crônica avançada são mais propensos a exigir outros procedimentos para recidiva de veias varicosas. Ainda não está estabelecido se a gravidade da insuficiência venosa é um fator que influencia a taxa de oclusão de veias safenas tratadas por endolaser. Objetivos Analisar a taxa de oclusão dos segmentos venosos tratados com endolaser e correlacionar com o Venous Clinical Severity Score (VCSS) e a classificação Clínica-Etiológica-Anatômica-Patológica (CEAP) dos pacientes. Métodos Análise retrospectiva de coorte de pacientes operados com endolaser 1.470 nm entre novembro/2012 a março/2020. Foram realizadas estatística descritiva e curva de sobrevida de Kaplan-Meier com regressão de Cox para grupos de VCSS e CEAP. Resultados Foram analisados 170 pacientes e 180 segmentos venosos; a idade média foi de 44,3 ± 9,2, sendo a maioria do sexo feminino (71%). A densidade de energia média utilizada na veia safena magna foi 49,2 ± 8,3 J/cm. As principais complicações foram dor no trajeto da safena (12,2%) e parestesias após 6 meses (17,2%). Não houve diferença na taxa de oclusão venosa entre grupos com VCSS ≤ 7 e VCSS > 7 (p = 0,067). O grupo de pacientes com CEAP agrupada C4-C5-C6 teve taxa de oclusão menor em relação ao grupo C2-C3 [hazard ratio (HR) = 3,22; intervalo de confiança (IC) 1,85, 5,61; p = 0,001]. Conclusões As taxas de oclusão de segmentos venosos tratados com endolaser foram menores na presença de classificações CEAP avançadas. Nesses pacientes, provavelmente deve-se despender mais energia para o tratamento eficaz das safenas.
FACTORS ASSOCIATED TO ALCOHOL USE BY ADOLESCENTS
Authors: Almeida Camila Souza de , Abreu Mery Natali Silva , Andrade Silmara Nunes , Lana Francisco Carlos Félix
Published: April 2021

ABSTRACT Objective to analyze the association between alcohol use by adolescents and environmental, family and social relations factors. Method and epidemiological study, of the cross-sectional cohort type, with a sample consisting of 303 students from the Brazilian 9thgrade of elementary level of public and private schools in Divinópolis, Minas Gerais, Brazil. Data was collected through the replication of the “General Information” and “Use of Alcohol” modules from the National Survey of School Health - 2015. The answer variable was alcohol consumption in life, associating it with explanatory variables related to: living with parents, maternal schooling, administrative dependency of the school, alcohol use by friends, and future perspectives. Univariate and multivariate analyses were used using Pearson's chi-square tests and Poisson's model for robust variances. Results an association was found in the multivariate analysis between consumption of beverages and intending to study only until high school or technical school (p=0.007), continuing to study and work (p=0.003), not living with parents (p=0.010), and having friends who make use alcohol (p=0.009). Conclusion social relationships were the most relevant factor for alcohol consumption by adolescents, mainly influenced by friends who use it and by the interpersonal relationships established by them.
Processo de validação de instrumentos de autoavaliação da voz no Brasil
Authors: Almeida Larissa Nadjara , Nascimento João Agnaldo do , Behlau Mara , Roseno Antônio Vítor , Aguiar Alexandra , Almeida Anna Alice
Published: April 2021

RESUMO Objetivo caracterizar e refletir sobre o processo de equivalência cultural e/ou validação de instrumentos de autoavaliação vocal traduzidos e adaptados para o português brasileiro, utilizados na prática clínica e em pesquisas científicas. Estratégia de pesquisa Buscas realizadas nas bases de dados: SciELO, LILACS, PubMed e The Cochrane Library. Critérios de seleção estudos selecionados quanto à presença dos descritores citados em seu título, resumo ou lista de descritores; artigos de validação de instrumento de autoavaliação em voz, ou com o objetivo de realizar equivalência cultural; direcionados à população brasileira; estudos originais com amostra de seres humanos, independentemente da idade do ciclo vital, tipo de disfonia ou sintomas vocais. Resultados nove artigos selecionados. Qualidade de vida em voz e desvantagem vocal foram os construtos mais abordados. A maioria das validações ocorreu na Região Sudeste do Brasil. A maior parte dos escores dos instrumentos foi calculada por somatório simples das respostas dos participantes nos itens; pontos de corte nem sempre foram apresentados. Os domínios dos instrumentos, bem como os itens que os compunham, foram mantidos conforme apresentado no instrumento em sua língua original. A estatística mais comum para análise dos instrumentos foi o coeficiente Alfa de Crombach. Conclusão os construtos mais abordados nos artigos selecionados foram qualidade de vida em voz e índice de desvantagem vocal. Os instrumentos foram considerados válidos e sensíveis para autoavaliação vocal, mesmo quando não consideradas as etapas propostas internacionalmente para validação de instrumentos em saúde.
Rodízio de postos de trabalho como exigência legal: análise da aceitação e percepção de trabalhadores do abate de bovinos
Authors: Messias Iracimara de Anchieta , Nascimento Adelaide , Rocha Raoni
Published: April 2021

Este artigo apresenta experiência de abordagem participativa preliminar à implantação da NR-36, que regula o trabalho em empresas produtoras de carne e derivados. Apesar de a normativa prever a participação do trabalhador nos processos de implantação de rodízio de postos, não esclarece como fazê-lo. O estudo foi desenvolvido no setor de abate de bovinos utilizando dois métodos complementares entre si: observações do trabalho in loco, para seleção dos postos prioritariamente elegíveis ao rodízio, e levantamento da percepção argumentada dos trabalhadores sobre o nível de aceitação de realização do rodízio nos postos selecionados. A princípio, 72% dos trabalhadores não aceitavam realizar o rodízio. Após inclusão e participação no processo de implantação, 86% dos trabalhadores da área suja e 64% da área limpa concordaram em realizar. Como evidências das vantagens em realizar rodízio, a variabilidade no trabalho (30%), aprendizado e ganho de experiência (40%), mudanças de movimentos (35%) e descanso físico (32%) se destacam. Como desvantagens, sobressaem o medo de acidentes (30%) e o medo da mudança e do desconhecido (25%). Concluímos que a abordagem participativa preliminar às mudanças de desenhos organizacionais contribui na compreensão e percepção dos trabalhadores sobre as vantagens e desvantagens do rodízio, indicando melhoria dos processos no cumprimento das exigências legais.
Briefing: Bringing clarity and new understanding of smart and modular integrated construction
Authors: Pan Wei , Zhang Zhiqian , Yang Yi
Published: April 2021

Modular construction has been promoted worldwide, with well demonstrated benefits. Modular integrated construction (MiC) was recently established in Hong Kong with the focus on integrated solutions to address high-rise buildings in high-density cities for productivity and competitiveness. Nevertheless, insufficient and inconsistent understanding exists. The University of Hong Kong has recently launched A Glossary of Modular Integrated Construction, which defines and illustrates over 170 terms related to MiC, off-site construction and smart project delivery, aiming at synergised understanding. The Glossary brings clarity and new understanding of modular and smart construction to the industry and community. With a focus on future building development in high-rise high-density contexts, the Glossary should become an important aid for achieving wider adoption of modular construction and smart technologies.
Calcitonin Induces 25-Hydroxyvitamin D3 1α-Hydroxylase mRNA Expression via Protein Kinase C Pathway in LLC-PK1 Cells
Authors: YOSHIDA NORIKO , YOSHIDA TADASHI , NAKAMURA AKIRA , MONKAWA TOSHIAKI , HAYASHI MATSUHIKO , SARUTA TAKAO
Published: April 2021

The biosynthesis of 1α, 25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 is catalyzed by 25-hydroxyvitamin D3 1α-hydroxylase (CYP27B1) in renal proximal tubules. It was recently demonstrated that LLC-PK1 cells express CYP27B1 mRNA, which is regulated by intracellular cAMP but not vitamin D3. To clarify the effect of calcitonin on vitamin D3 metabolism in vitro, LLC-PK1 cells were incubated with hormonal factors, and expression of CYP27B1 mRNA was measured by quantitative reverse transcription-PCR. Calcitonin at 100 nmol/L significantly increased CYP27B1 mRNA expression by 24 h (271 ± 21% of control). Incubation with calcitonin over a range of 1 μmol/L to 1 pmol/L resulted in a concentration-dependent increase in CYP27B1 mRNA levels. It is known that the calcitonin receptor has dual intracellular signaling pathways, via protein kinases A and C. Both 500 μmol/L 8-bromo-cAMP, a protein kinase A activator, and 100 nmol/L phorbol 12-myristate 13-acetate, a protein kinase C activator, increased CYP27B1 mRNA levels at 24 h (207 ± 54 and 246 ± 58% of control, respectively). However, calcitonin-induced CYP27B1 mRNA expression was only inhibited by the protein kinase C inhibitors staurosporine and calphostin C. The protein kinase A inhibitors Rp-cAMPS at 10 and 100 μmol/L and H-89 at 10 μmol/L had no effect on the action of calcitonin, in spite of cAMP-activation by calcitonin. The present data suggest that calcitonin upregulates CYP27B1 mRNA expression via the protein kinase C pathway in LLC-PK1 cells.
Chronic Reduction in Renal Mass in the Rat Attenuates Ischemia/Reperfusion Injury and Does Not Impair Tubular Regeneration
Authors: VERCAUTEREN SVEN R. , YSEBAERT DIRK K. , DE GREEF KATHLEEN E. , EYSKENS ERIK J. , DE BROE MARC E.
Published: April 2021

It is not known whether a kidney with chronic structural and functional changes is more vulnerable to an acute renal insult, and whether its regeneration capacity after injury is altered. To study this question, Lewis rats were submitted 10 wk after 5/6 nephrectomy to an ischemic insult of 60 min (remnant kidney [RK] group). Functional and morphologic data of the RK group were compared with data obtained in 10-wk uninephrectomized (1K) and normal (2K) Lewis rats with unilateral and bilateral renal ischemia, respectively. The acute postischemic decrease in creatinine clearance was smallest in the RK group, followed by the 2K and 1K groups, respectively. At days 1 and 3, fewer proximal tubules in the outer stripe of the outer medulla of the RK and 2K groups had undergone acute tubular necrosis compared with the 1K group. The mean percentage of tubules with signs of regeneration was maximal at day 3 in the three experimental groups. At day 10, regeneration was almost complete in the three groups. The number of leukocytes (OX1+ cells) present in the RK before ischemia did not increase after ischemia/reperfusion injury (377 ± 146 cells/mm2 at day 0) in contrast to the 1K and 2K groups. In the latter groups, the number of leukocytes had increased gradually, reaching a maximum at day 15 (1K: 960 ± 308 cells/mm2) and day 10 (2K: 668 ± 164 cells/mm2), respectively. In conclusion, this study has shown that an RK exhibiting chronic morphologic changes of interstitial fibrosis and tubular atrophy is protected against ischemia/reperfusion injury, and that its regeneration capacity is preserved. The reperfusion injury is not followed by further accumulation of leukocytes, which were already present in the RK before ischemia.
The PlA2 Polymorphism of the Platelet Glycoprotein IIIA Gene as a Risk Factor for Acute Renal Allograft Rejection
Authors: SALIDO EDUARDO , MARTÍN BASILIO , BARRIOS YSAMAR , LINARES JOSÉ D. , HERNÁNDEZ DOMINGO , COBOS MARIAN , CHECA MARÍA D. , HORTAL LUIS , FERNÁNDEZ ANA , GARCÍA JOSÉ J. , TORRES ARMANDO
Published: April 2021

Glycoprotein IIIa/IIb is a membrane receptor for fibrinogen and von Willebrand factor that plays an important role in platelet aggregation. The β integrin chain of this receptor, GPIIIa, is polymorphic, and the allele known as PlA2 has been associated with coronary thrombosis. The GPIIIa genotype of a cohort of 119 consecutive renal allograft recipients (46.3 ± 13 yr; 85 M/34 F; 24.4% diabetic patients) was determined by PCR-restriction fragment length polymorphism, and those patients were followed for at least 12 mo. From 119 patients with at least 1 yr of follow-up, those who suffered an acute rejection (n = 52) showed a lower proportion of HLA-DR β1 identity with the donor (7.7% versus 23.9%; P = 0.03), a higher proportion of cytomegalovirus-positive (CMV+) donors/CMV- recipients (21% versus 7.5%; P = 0.05), and the PlA2 allele was more frequent (48.1% versus 26.9%; P = 0.02) compared with patients free of acute rejection (n = 67). No other variable was associated with acute rejection in the univariate analysis. The impact of the three above-mentioned significant variables on acute rejection was analyzed by stepwise logistic regression. The presence of the PlA2 allele yielded an odds ratio of 2.75 (95% confidence interval, 1.01 to 7.93) and an HLA-DR β1 identity of 0.2 (95% confidence interval, 0.06 to 0.99) for suffering an acute rejection episode. In addition, the serum creatinine at discharge was higher in PlA2-positive versus PlA2-negative patients (2.2 ± 1.6 versus 1.5 ± 0.6 mg/dl, respectively; P = 0.01), and the prevalence of proteinuria > 1.5 g/d 1 yr after transplantation was significantly higher among patients showing the PlA2 allele (16% versus 3%; P = 0.02). Finally, in the entire cohort of patients, the 2-yr graft survival was significantly lower in PlA2-positive (n = 43) compared with PlA2-negative (n = 76) patients (85.7% versus 97.2%; P = 0.015). No differences were found in patient survival (95.2% versus 98.7%, respectively). Proportional hazards regression analysis (Cox regression model) confirmed that serum creatinine level at discharge is the best predictor of allograft survival, followed by CMV status, delayed graft function, and the glycoprotein IIIa/IIb genotype. The PlA2 polymorphism is an independent risk factor for acute renal graft rejection, affecting short-term graft survival. Future studies aimed at preventing the hemostatic imbalance favoring platelet aggregation associated with this polymorphism may be important in preventing acute rejection and its impact on chronic rejection.
Beneficial Effect of Serotonin 5-HT2-Receptor Antagonism on Renal Blood Flow Autoregulation in Cyclosporin-Treated Rats
Authors: VERBEKE MARLEEN , VAN DE VOORDE JOHAN , DE RIDDER LEO , LAMEIRE NORBERT
Published: April 2021

Renal blood flow (RBF) autoregulation reappears in postischemic rat kidneys during serotonin (5-HT2) antagonism. The aim of the present study was to analyze whether 5-HT2 antagonism can ameliorate impaired RBF autoregulation in rats treated with 20 mg/kg per d cyclosporin A during 10 d. Autoregulation of RBF was assessed during stepwise lowering of renal perfusion pressure from 110 to 70 mmHg by gradual compression of the aorta. Autoregulation was lost in the cyclosporin A-treated rats. During administration of the 5-HT2 antagonist ritanserin (0.6 mg/kg intravenous bolus, followed by 1.2 mg/kg per h intravenous infusion during 1 h), autoregulation acutely reappeared. Intrarenal bolus injections of a selective 5-HT2-agonist, 2,5 dimethoxy-4-iodoamphetamine hydrochloride, elicited a significantly stronger renal vasocontraction in cyclosporin A-treated rats than in control rats. This finding was also observed with serotonin after nitric oxide-synthase blockade. These results (1) show the importance of 5-HT2-receptor-mediated vasoconstriction in the suppression of vasodilatory autoregulation of RBF in experimental cyclosporin A-induced renal dysfunction and (2) demonstrate that the complete loss of RBF autoregulation is not due to damage of the vascular smooth muscle cells.
Intrarenal Insulin-Like Growth Factor-1 Axis after Unilateral Nephrectomy in Rat
Authors: FERVENZA FERNANDO C. , TSAO TANNY , HSU FAY , RABKIN RALPH
Published: April 2021

It has been suggested that insulin-like growth factor-1 (IGF-1) may play a role in early compensatory renal growth. Since IGF-1 action is influenced by IGF binding proteins (IGFBP), this study was conducted to characterize the changes in gene expression not only of IGF-1 and its receptor, but also of IGFBP in the hypertrophying kidney of adult and weanling rats 1 wk after removal of the other kidney. At this time, there were distinct age-dependent changes in the renal IGF-1 axis. In the mature kidney, IGF-1 mRNA levels fell without a change in kidney IGF-1 peptide content. Likewise, although IGFBP-2, -3, and -5 mRNA levels fell, membrane-associated IGFBP did not change. IGF-1 receptor mRNA levels and IGF-1 receptor number both fell. In the weanling kidneys, IGF-1 mRNA and peptide levels and IGF-1 receptor binding were unaltered. However, IGFBP-3, -4, and -5 mRNA levels were increased, as were plasma membrane-associated IGFBP. Although these changes in the intrarenal IGF-1 axis were distinct, it is difficult to conceive how in either the mature or immature rat they could contribute to the ongoing compensatory renal growth that occurs 1 wk after loss of kidney mass unless IGF-1 were acting in a synergistic manner with other growth promoters.
cGMP-Dependent and -Independent Inhibition of a K+ Conductance by Natriuretic Peptides
Authors: HIRSCH JOCHEN R. , MEYER MARKUS , MÄGERT HANS-JURGEN , FORSSMANN WOLF-GEORG , MOLLERUP STEEN , HERTER PETER , WEBER GERHARD , CERMAK RAINER , ANKORINA-STARK IEVA , SCHLATTER EBERHARD , KRUHØFFER MOGENS
Published: April 2021

In immortalized human kidney epithelial (IHKE-1) cells derived from proximal tubules, two natriuretic peptide receptors (NPR) were identified. In addition to NPR-A, which is bound by atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and urodilatin (URO), a novel form of NPR-B that might be bound by C-type natriuretic peptide (CNP) was identified using PCR. This novel splice variant of NPR-B (NPR-Bi) was also found in human kidney. Whereas ANP, BNP, and URO increased intracellular cGMP levels in IHKE-1 cells in a concentration-dependent manner, CNP had no effect on cGMP levels. To determine the physiologic responses to these agonists in IHKE-1 cells, the membrane voltage (V
m) was monitored using the slow whole-cell patch-clamp technique. ANP (10 nM), BNP (10 nM), and URO (16 nM) depolarized these cells by 3 to 4 mV (n = 47, 7, and 16, respectively), an effect that could be mimicked by 0.1 mM 8-Br-cGMP (n = 15). The effects of ANP and 8-Br-cGMP were not additive (n = 4). CNP (10 nM) also depolarized these cells, by 3 ± 1 mV (n = 28), despite the absence of an increase in cellular cGMP levels, indicating a cGMP-independent mechanism. In the presence of CNP, 8-Br-cGMP further depolarized V
m significantly, by 1.6 ± 0.3 mV (n = 5). The depolarizations by ANP were completely abolished in the presence of Ba2+ (1 mM, n = 4) and thus can be related to inhibition of a K+ conductance in the luminal membrane of IHKE-1 cells. The depolarizations attributable to CNP were completely blocked when genistein (10 μM, n = 6), an inhibitor of tyrosine kinases, was present. These findings indicate that natriuretic peptides regulate electrogenic transport processes via cGMP-dependent and -independent pathways that influence the V
m of IHKE-1 cells.
Mechanisms of Mitogen-Activated Protein Kinase Activation in Experimental Diabetes
Authors: AWAZU MIDORI , ISHIKURA KENJI , HIDA MARIKO , HOSHIYA MAKIKO
Published: April 2021

Various growth factors and vasoactive substances are implicated in the pathogenesis of renal growth seen in early diabetes mellitus (DM). Mitogen-activated protein kinase (MAPK) is an important mediator of these extracellular stimuli. Protein kinase C (PKC), an enzyme known to be stimulated in DM, also activates MAPK. Thus, MAPK activity was examined in glomeruli from streptozotocin-induced DM rats. MAPK activity, measured as myelin basic protein kinase, was elevated by approximately 50% in DM versus controls (CON). Increased protein contents of p42mapk and p44mapk, as well as increased tyrosine phosphorylation and mobility shift of p42mapk, were also observed in DM. Tyrosine dephosphorylation of pp42mapk, on the other hand, assessed by incubating glomerular membrane with or without sodium orthovanadate (vanadate), was significantly diminished in DM. Protein expression of MAPK phosphatase-1 (MKP-1), a dual specificity phosphatase that inactivates MAPK, was approximately 60% of CON. Reduction in MKP-1 was reproduced in cultured mesangial cells grown under high glucose (30 mM; HG). The suppression of MKP-1 was PKC-dependent since incubation of HG cells with phorbol 12-myristate 13-acetate for 24 h abolished it. Furthermore, calcium ionophore A23187 reversed the suppression, suggesting that blunted Ca2+ signalling, characteristic of HG cells secondary to PKC stimulation, may be the cause. These results demonstrate that glomerular MAPK is activated in DM by multiple mechanisms i.e., increases in protein contents, increased phosphorylation, and decreased dephosphorylation of the enzyme due to suppression of MKP-1. These alterations may have an implication in the pathogenesis of diabetic nephropathy.
Cloning of Porcine 25-Hydroxyvitamin D3 1α-Hydroxylase and Its Regulation by cAMP in LLC-PK1 Cells
Authors: YOSHIDA TADASHI , YOSHIDA NORIKO , NAKAMURA AKIRA , MONKAWA TOSHIAKI , HAYASHI MATSUHIKO , SARUTA TAKAO
Published: April 2021

The 25-hydroxyvitamin D3 1α-hydroxylase, also referred to as CYP27B1, is a mitochondrial cytochrome P450 enzyme that catalyzes the biosynthesis of 1α, 25-dihydroxyvitamin D3 (1α,25(OH)2D3) from 25-hydroxyvitamin D3 in renal proximal tubular cells. Recently, human, mouse, and rat CYP27B1 cDNA have been cloned, however the gene regulation has not been fully elucidated. In the present study, porcine CYP27B1 cDNA was cloned, and the effects of cAMP and vitamin D3 on the regulation of CYP27B1 mRNA expression in LLC-PK1 cells were examined. PCR cloning revealed that porcine CYP27B1 cDNA consisted of 2316 bp, encoding a protein of 504 amino acids. The deduced amino acid sequence showed over 80% identity to the human, mouse, and rat enzyme. LLC-PK1 cells were incubated with humoral factors, and expression of CYP27B1 mRNA was measured by a quantitative reverse transcription-PCR. At the completion of 3-, 6-, 12-, and 24-h incubations, 500 μmol/L 8-bromo-cAMP had significantly increased CYP27B1 mRNA expression (260 to 340%). The adenylate cyclase activator forskolin at 50 μmol/L also had a stimulatory effect at 6 h (190%). Moreover, the protein kinase A inhibitor H-89 reduced the cAMP effect. On the other hand, 1α,25(OH)2D3 had no effect on CYP27B1 mRNA expression at 10 and 100 nmol/L, whereas expression of 25-hydroxyvitamin D3 24-hydroxylase (CYP24) mRNA was markedly increased by 1α,25(OH)2D3. These findings suggest that LLC-PK1 cells express CYP27B1 mRNA, and that cAMP is an upregulating factor of the CYP27B1 gene in vitro.
In Chronic Nephropathies Prolonged ACE Inhibition Can Induce Remission
Authors: RUGGENENTI PIERO , PERNA ANNALISA , BENINI ROBERTO , BERTANI TULLIO , ZOCCALI CARMINE , MAGGIORE QUIRINO , SALVADORI MAURIZIO , REMUZZI GIUSEPPE
Published: April 2021

The Ramipril Efficacy in Nephropathy Core and Follow-Up Study found that ≥36 mo of continued ramipril therapy decreased substantially the risk of end-stage renal failure (ESRF) in patients with chronic nephropathies and a urinary protein excretion rate ≥3 g/24 h. This study investigates the time-dependent changes in GFR in these patients and in control subjects who were randomized to conventional therapy during the Core period and switched to ramipril during the Follow-Up study. Analyses included 150 patients (continued ramipril: n = 74; switched to ramipril: n = 76) who had at least three GFR measurements (including baseline) during the whole observation period and a subgroup of 43 patients (continued ramipril: n = 26; switched to ramipril: n = 17) who had at least six GFR measurements, including at least three on the Core and at least three on the Follow-Up study. Ramipril (1.25 to 5 mg/d) and conventional therapy were targeted at achieving a diastolic BP below 90 mmHg. The main efficacy variables were GFR and ESRF (need for dialysis). Analysis was by intention to treat. Throughout the study, the mean ± SEM rate of GFR decline (ΔGFR) was significantly lower in patients continued on ramipril compared to those switched to ramipril (0.51 ± 0.09 versus 0.76 ± 0.10 ml/min per 1.73 m2 per mo, P < 0.03). In patients on continued ramipril who had at least six GFR measured—but not in control subjects—ΔGFR progressively improved with time and, in the cohort with the longest follow-up, decreased from (in ml/min per 1.73 m2 per mo): 0.16 ± 0.12 (at 18 mo) to 0.10 ± 0.05 (at 60 mo). This rate was about 10-fold slower compared to patients on conventional therapy during the REIN Core study. Analyses of the individual slopes found that at the end of the follow-up, 10 of 26 patients on continued ramipril therapy had a positive ΔGFR and another 10 patients had an improvement of ΔGFR while on ramipril therapy. ΔGFR significantly improved in parallel with a significant reduction in proteinuria. Changes in ΔGFR (P = 0.0001) and proteinuria (P = 0.04) were significantly different in the two groups. Baseline characteristics and changes in systolic and diastolic BP and 24-h urine urea and sodium excretion were comparable. The present results offer evidence that in chronic nephropathies, the tendency of GFR to decline with time can be effectively halted, even in patients with remarkably severe disease.
Calcitonin Stimulates Lysosomal Enzyme Release and Uptake in LLC-PK1 Cells
Authors: GOTO MASAKO , MIZUNASHI KAZUTOSHI
Published: April 2021

Renal tubular targeted hormones increase urinary excretion of a lysosomal enzyme, N-acetyl-β-D-glucosaminidase (NAG). To elucidate the mechanism of this event, the calcitonin effect on NAG handling by LLC-PK1 cells was examined. Calcitonin (1 nM to 1 μM), phorbol myristate (10 nM to 1 μM), and ionomycin (1 to 10 μM) promoted NAG release without any increase in lactate dehydrogenase release or any reduction of mitochondrial dehydrogenase activity. Treatment with 100 nM calphostin C or 50 μM KN-93 partially reversed the calcitonin effect on NAG release. Calcitonin promoted secretion of fluorescence ceramide, a reporter of protein transport from Golgi apparatus to cell surface. Calcitonin-stimulated NAG release was partially inhibited by 10 μg/ml brefeldin A, a blocker of protein transport through the Golgi apparatus. Calcitonin accelerated cellular uptake of exogenous NAG, which was inhibited by low temperature, 0.1 mM monodansyl cadaverine (receptor-mediated endocytosis inhibitor), and 10 mM mannose-6-phosphate. Furthermore, calcitonin promoted progression of intracellular membranes stained by a fluorescence membrane marker, styryl pyridinium dye, from cell periphery to perinuclear regions (commonly referred to as recycling vesicles) and increased dye release from preloaded cells. Fluorescence release from the cells preloaded with FITC-labeled NAG or albumin was also stimulated by calcitonin. These calcitonin effects on endocytotic and re-exocytotic pathways were inhibited by 100 nM cytochalasin D, 100 nM nocodazole, 0.1 to 1 μM bafilomycin A1, or 0.1 mM monodansyl cadaverine. Increased urinary NAG excretion has been considered to reflect renal tubular damage. However, it was demonstrated here that stimulation of secretory and recycling pathways may be an alternative mechanism for calcitonin-induced enzymuria, which will become a new indicator of renal tubular response to this hormone.