bluuebunny/crossref_metadata_2025 huggingface dataset:
Metaheuristic algorithms for one-dimensional bin-packing problems: A survey of recent advances and applications
Authors: Munien Chanaleä , Ezugwu Absalom E.
Published: April 2021

The bin-packing problem (BPP) is an age-old NP-hard combinatorial optimization problem, which is defined as the placement of a set of different-sized items into identical bins such that the number of containers used is optimally minimized. Besides, different variations of the problem do exist in practice depending on the bins dimension, placement constraints, and priority. More so, there are several important real-world applications of the BPP, especially in cutting industries, transportation, warehousing, and supply chain management. Due to the practical relevance of this problem, researchers are consistently investigating new and improved techniques to solve the problem optimally. Nature-inspired metaheuristics are powerful algorithms that have proven their incredible capability of solving challenging and complex optimization problems, including several variants of BPPs. However, no comprehensive literature review exists on the applications of the metaheuristic approaches to solve the BPPs. Therefore, to fill this gap, this article presents a survey of the recent advances achieved for the one-dimensional BPP, with specific emphasis on population-based metaheuristic algorithms. We believe that this article can serve as a reference guide for researchers to explore and develop more robust state-of-the-art metaheuristics algorithms for solving the emerging variants of the bin-parking problems.
Chromate and molybdate pigments
Authors: Pfaff Gerhard
Published: April 2021

Chromate and molybdate pigments are representatives of the inorganic yellow, orange and red pigments. They are characterized by excellent optical and application properties in particular regarding brightness of shade, hiding power, tinting strength, and weather fastness. The declining use of lead- and chromate-containing materials in the last decades is a result of the environmental discussion and the development of less problematic substitute products, especially of bismuth vanadate and high-value organic, temperature-stable yellow and red pigments.
PSICODRAMA E MÉTODOS DE AÇÃO ON-LINE: TEORIAS E PRÁTICAS
Authors: Nery Maria da Penha
Published: April 2021

Trata-se de um estudo de práticas psicoterápicas e socioterápicas desenvolvidas em ambiente virtual, no período de pandemia da Covid-19. Foram realizados métodos de ação on-line, dentre eles: psicodramas, sociodramas, teatros espontâneos e jogos dramáticos. Como objetivo, buscou-se compreender as especificidades desses métodos. Metodologicamente, foram realizadas análises da informação e da sociodinâmica desses encontros, por meio das quais confirmamos ou refutamos hipóteses relativas às especificidades e aos efeitos terapêuticos do atendimento on-line. A partir das análises, foram encontrados alguns fenômenos, definidos teórica e praticamente, dentre eles: realidade hipersuplementar, entrecruzamento de cenas, tele virtual, vínculo terapêutico virtual, corporalidade condensada, fala-ação, matriz sociocultural dinâmica e papel psicodramático-virtual.
PSYCHOLOGISTS AND PSYCHODRAMATISTS IN EDUCATION: AN ONLINE PROJECT DEVELOPED DURING THE PANDEMIC
Authors: Dias Alcione , Barros Luiza Maria Soares , Urt Sonia
Published: April 2021

This article presents the socionomic project Ouvindo a Escola (Listening the School) and its developments, a set of socio-psychodramatic practices carried out during the year 2020, generated in remote mode and in times of pandemic. We start by making a brief history of Educational Psychology and continue pointing Psychodramatic Pedagogy as a transformative perspective in the socio-educational field. The project involved 11 psychodramatists, 39 teachers and 15 public school workers. We intend to give visibility to referenced practices that can contribute to Critical School Psychology within the scope of public education and propose ways of action, in times of social isolation.
PSICODRAMA ON-LINE
Authors: Ros Goyo Armañanzas
Published: April 2021

Hago un breve recorrido por mi experiencia a lo largo de la pandemia. En ella se han mezclado los cambios profesionales y su paso a la modalidad online, las vivencias emocionales personales y las colectivas. Aporto unas ideas, cara a la evolución emocional colectiva a lo largo de la pandemia hasta este momento. Abordo mi actitud ante posiciones negacionistas y como he podido aproximarme emocionalmente a ellas, gracias al psicodrama. Hago referencia la ejercicio que me ayudó a empatizar con esas posiciones, algo particular mente difícil, dentro de un movimiento internacional de psicodramatistas iniciado en Argentina. Me detengo en algunos elementos que cambian al cambiar del espacio presencial al espacio online. Doy algunas ideas de caldeamientos, elección de protagonista y cierres.
ONLINE SOCIATRIC PRACTICES: NEW STUDIES AND EXPERIENCES
Authors: Belém Aline Oliveira , Nery Maria da Penha
Published: April 2021

The Revista Brasileira de Psicodrama (RBP) has published several articles on Psychodrama online for the past two years, which contribute to our reflections and professional practices. This RBP issue seeks to complement this repertoire and focuses on the studies of psychodramatists on their experiences and strategies in social practice in virtual environments.
PRÁTICAS SOCIÁTRICAS ON-LINE: NOVOS ESTUDOS E EXPERIÊNCIAS
Authors: Belém Aline Oliveira , Nery Maria da Penha
Published: April 2021

A Revista Brasileira de Psicodrama (RBP), nos últimos dois anos, tem publicado diversos artigos sobre Psicodrama on-line, que contribuem para nossas reflexões e práticas profissionais. Esse número da RBP busca complementar esse repertório, e tem como foco os estudos de psicodramatistas sobre suas experiências e estratégias na prática sociátrica em ambientes virtuais.
Restructuring state power in Sudan
Authors: Tchie Andrew , Ali Hamid E
Published: April 2021

Developing post-conflict economic policies in Sudan remains a significant challenge for the Sudanese transitional government and the international community. This article argues that understanding the conflict, its costs and the progress made during the current peace agreement are essential for advancing policy reforms in Sudan. The Sudanese transitional government has attempted to implement reforms, but little progress has been made because the civilian elements operate outside of the existing state power. The previous regimes policies sustained conflict(s) through both passive and active enablement of the Sudanese security forces, which means that the restructuring of state power is essential to place Sudan on the right course towards sustained democracy. This article posits that addressing structural reforms in Sudan means establishing control over the economy, defense, and security sectors.
Mitogen-Activated Protein Kinase Phosphorylation in Kidneys of βs Sickle Cell Mice
Authors: KIROYCHEVA MILITZA , AHMED FAYYAZ , ANTHONY GILLIAN M. , SZABO CSABA , SOUTHAN GARRY J. , BANK NORMAN
Published: April 2021

Previous studies in βs sickle cell mice demonstrated renal immunostaining for nitrotyrosine, which is putative evidence of peroxynitrite (ONOO-) formation. ONOO- is known to nitrate tyrosine residues of various enzymes, thereby interfering with phosphorylation and inactivating them. The present study examined the state of phosphorylation of mitogen-activated protein (MAP) kinase signal transduction enzymes, i.e., p38, c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Western blot performed with antibodies directed against specific phosphorylated threonine/tyrosine residues of these enzymes demonstrated reduced phosphorylation of renal p38 and a trend toward reduced phosphorylation of ERK. In contrast, phosphorylation of renal JNK was markedly increased compared with normal mice. The abundance of MAP kinase phosphatase-1 (MKP-1), a key upstream enzyme that modulates phosphorylation of MAP kinases, was not different in βs
versus normal mice. To determine whether nitration of tyrosine by ONOO- was responsible for reduced phosphorylation of p38 and ERK, mercaptoethylguanidine (MEG), a compound known to reduce inducible isoform of nitric oxide synthase activity and to scavenge ONOO-, was administered to βs mice for 5 d. MEG was found to restore phosphorylation of p38 and ERK toward normal levels. These observations provide evidence that ONOO- (or closely related reaction products of NO) contributes to dephosphorylation of p38 and ERK, and presumably reduces activity of these enzymes. The increased phosphorylation of JNK, which suggests activation of this signaling pathway by extracellular stress signals, may play a role in apoptosis in the kidneys of these mice. The changes in phosphorylation of MAP kinase pathways found in this study could have important consequences for regulation of nuclear transcription factors, and thus renal function and pathology in sickle cell kidneys.
C-Terminal Parathyroid Hormone-Related Protein Increases Vascular Endothelial Growth Factor in Human Osteoblastic Cells
Authors: ESBRIT PEDRO , ALVAREZ-ARROYO MARIA VICTORIA , DE MIGUEL FERNANDO , MARTIN OLGA , MARTINEZ MARIA EUGENIA , CARAMELO CARLOS
Published: April 2021

The N-terminal region of parathyroid hormone (PTH) and PTH-related protein (PTHrP) interacts with a common PTH/PTHrP receptor in osteoblasts. These cells synthesize PTHrP, but its role in bone turnover is unclear. Intermittent treatment with N-terminal PTHrP or PTH stimulates bone growth in vivo, possibly by increasing local bone factors. In addition, C-terminal PTHrP (107-139), which does not bind to the PTH/PTHrP receptor, appears to affect bone resorption in vivo and in vitro, although its effect on bone formation in vivo remains controversial. Bone angiogenesis is an often overlooked but critical event in the process of bone remodeling. Recently, PTH (1-34) has been shown to induce gene expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, by osteoblastic cells. However, no data are available on the effect of PTHrP (107-139) on VEGF expression in these cells. Using semiquantitative reverse transcription followed by PCR, we found that PTHrP (107-139), between 10 nM and 1 pM, increased VEGF mRNA in human osteoblastic (hOB) cells from trabecular bone. This effect of this agonist, at 10 nM, was maximal (fivefold for VEGF165, and twofold for VEGF121, compared to control) within 1 to 4 h. This effect was similar to that induced by PTHrP (1-34) in these cells, as well as in human osteosarcoma MG-63 cells, using Northern blot analysis. Moreover, the effect of both peptides, added together at 100 pM, was not higher than that observed with each peptide alone in hOB cells. The effects of PTHrP (107-139) and that of PTHrP (1-34) were abolished by actinomycin D in hOB cells. In these cells, the protein kinase C inhibitor staurosporine, but not the protein kinase A inhibitor H89, inhibited the increase in VEGF mRNA induced by 10 nM PTHrP (107-139). PTHrP (107-139), at 10 nM, also stimulated cytosolic VEGF immunostaining in hOB cells, and VEGF secretion into the medium conditioned by hOB or MG-63 cells for 24 h, which was (ng/mg protein): 10 ± 1 or 5 ± 3 (control), respectively, and 21 ± 1 or 11 ± 2 (PTHrP [107-139]-stimulated), respectively. Furthermore, medium conditioned by these cells for 24 h in the presence of 10 nM PTHrP (107-139), with or without 10 nM PTHrP (1-34), increased about 30% bovine aortic endothelial cell (BAEC) growth at 48 h. This effect was inhibited by adding a specific anti-VEGF antibody to the BAEC incubation medium. These findings demonstrate that the C-terminal domain of PTHrP induces expression and secretion of VEGF, a main angiogenic factor, in hOB cells and MG-63 cells. This relationship between PTHrP and VEGF has potential implications for both bone vascularization and bone formation, and neoangiogenesis in PTHrP-producing tumors.
High Prevalence of Low Bone Turnover and Occurrence of Osteomalacia after Kidney Transplantation
Authors: MONIER-FAUGERE MARIE-CLAUDE , MAWAD HANNA , QI QUANLE , FRIEDLER ROBERT M. , MALLUCHE HARTMUT H.
Published: April 2021

Kidney transplantation corrects most of the metabolic abnormalities that cause renal osteodystrophy. However, many transplanted patients develop osteoporosis and other bone lesions that are related, at least in part, to their immunosuppressive regimen. The precise histologic patterns of bone disease after transplantation are not well defined. In a study designed to investigate this issue, 57 adult posttransplant patients agreed to undergo bone biopsies and blood drawings. There were 32 men and 25 women, mean age 45 ± 2 yr, who had received a kidney transplantation 5.6 ± 0.8 yr before biopsy. History of bone pain, fractures, and avascular necrosis was found in 22, 12, and 7 patients, respectively. Serum creatinine was 1.68 ± 0.1 mg/dl, 21% of patients were hypercalcemic, 63.2% had elevated parathyroid hormone (PTH) (>65 pg/ml), and 91.2% had normal calcitriol levels. Cancellous bone volume/tissue volume was below normal compared to age- and gender-matched control subjects in 56.1% of patients. Bone turnover (activation frequency) was low in 45.6%, normal in 28.1%, and elevated in 26.3% of patients. Bone formation rate/bone surface was low in 59.7%, normal in 35%, and elevated in 5.3% of the patients. Erosion surface/bone surface was high in 21.1% of patients. Mineralization was prolonged in 87.5% of patients, including 9 patients with osteomalacia and 12 patients with focal osteomalacia. Cumulative and maintenance doses of prednisone and time elapsed since transplantation correlated negatively with bone volume and bone turnover (r = -0.32 to -0.59, P < 0.05 to 0.01), whereas cumulative doses of cyclosporine or azathioprine, age, gender, or serum PTH levels did not. Regression analysis identified prednisone as the main factor responsible for low bone volume and bone turnover (r = 0.54 and r = 0.43, P < 0.01). No factors were found to predict delayed mineralization. The present study shows that low bone volume, low bone turnover, and generalized or focal osteomalacia are frequent histologic features in transplanted patients. The effects of age, gender, PTH, and cyclosporine on bone volume and bone turnover are apparently overridden by the prominent effects of glucocorticoids. The prevalence of mineralization defect in the presence of normal serum levels of calcidiol and calcitriol suggests vitamin D resistance and deserves further study.
Urinary Protein Binding Does Not Affect Response to Furosemide in Patients with Nephrotic Syndrome
Authors: AGARWAL RAJIV , GORSKI J. CHRISTOPHER , SUNDBLAD KIMBERLY , BRATER D. CRAIG
Published: April 2021

Response to loop diuretics in patients with nephrotic syndrome (NS) is subnormal. Studies in animal models of NS have suggested that binding of diuretic to urinary albumin is one of the mechanisms that may be operative in this diuretic resistance. To explore this hypothesis, 12 patients with NS were studied to determine whether displacement from urinary protein binding with sulfisoxazole would restore response to 120 mg of furosemide. The study was stopped after treating seven patients because it was clear that sulfizoxazole had no effect. Sodium excretion (mean ± SD) from furosemide alone was 239 ± 90 versus 240 ± 115 mEq/8 h with sulfisoxazole. Sulfisoxazole had modest effects on serum pharmacokinetics of furosemide but had no effect on either the time course of furosemide urinary excretion or overall amount excreted: 49 ± 15 mg versus 54 ± 12 mg for furosemide alone and furosemide plus sulfisoxazole, respectively. It is concluded that urinary protein binding of loop diuretics is not a major mechanism for the diuretic resistance of NS. In turn, strategies aimed at displacing such binding are unlikely to be clinically helpful.
Effect of High Dose Folic Acid Therapy on Hyperhomocysteinemia in Hemodialysis Patients
Authors: SUNDER-PLASSMANN GERE , FO[Combining Diaeresis]DINGER MANUELA , BUCHMAYER HEIDI , PAPAGIANNOPOULOS MENELAOS , WOJCIK JADWIGA , KLETZMAYR JOSEF , ENZENBERGER BRIGITTE , JANATA OSKAR , WINKELMAYER WOLFGANG C. , PAUL GERNOT , AUINGER MARTIN , BARNAS URSULA , HO[Combining Diaeresis]RL WALTER H.
Published: April 2021

Homocysteine is associated with atherosclerosis and enhanced cardiovascular risk. In previous studies, treatment with folic acid up to 15 mg/d failed to correct hyperhomocysteinemia in the majority of end-stage renal disease patients. A dose of 30 or 60 mg of folic acid per day was compared with 15 mg/d in an attempt to normalize hyperhomocysteinemia in 150 hemodialysis patients. In a randomized, double-blind, multicenter study, 144 patients completed the 4-wk treatment period and 121 patients completed the 6-mo follow-up. Total homocysteine plasma levels were reduced by 32.1% (15 mg/d), 29.9% (30 mg/d), or 37.8% (60 mg/d) with no significant differences found between the three treatment groups. Baseline total homocysteine plasma concentration was an independent predictor of the response to folic acid therapy (P = 0.0001), whereas the 5,10-methylenetetrahydrofolate reductase polymorphisms (MTHFR 677C → T and 1298A → C) had no influence. Nevertheless, patients with the MTHFR 677TT genotype more frequently attained normal total homocysteine plasma levels than patients with the CC or CT genotype (P = 0.025). In response to 60 mg of folic acid per day, TT genotype patients had lower folate plasma levels compared to CC or CT genotype patients (P = 0.016). After completion of the 4-wk treatment period with 30 or 60 mg of folic acid per day, there was a marked rebound of total homocysteine plasma levels at the end of the follow-up in patients with the MTHFR 677TT genotype, which even exceeded baseline values in several patients (P = 0.0001). This study clearly demonstrates that doses of 30 or 60 mg of folic acid per day are not more effective than 15 mg/d in reducing hyperhomocysteinemia in regular hemodialysis patients. Patients with the MTHFR 677TT genotype are more likely to realize normal total homocysteine plasma levels. Folic acid at 30 or 60 mg/d but not 15 mg/d results in a rebound of total homocysteine plasma concentrations when treatment is stopped.
Primary Structure of Mouse and Rat Nephrin cDNA and Structure and Expression of the Mouse Gene
Authors: PUTAALA HELI , SAINIO KIRSI , SARIOLA HANNU , TRYGGVASON KARL
Published: April 2021

Nephrin is a central component of the glomerular podocyte slit diaphragm and is essential for the normal renal filtration process. This study describes the complete structure of the mouse nephrin gene, which was shown to be homologous to the human gene, the major difference being 30 exons in the mouse gene as opposed to 29 in human. The complete primary structure of mouse and rat nephrins was also determined. The sequence identity between the mouse and rat proteins was shown to be 93%, while both rodent proteins have only about 83% sequence identity with human nephrin. The availability of the three mammalian sequences is significant for the interpretation of sequence variants and mutations in the nephrin gene in patients with congenital nephrotic syndrome. In situ hybridization analyses of whole mouse embryos and tissues revealed high expression of nephrin in kidney glomeruli and, surprisingly, an intense and highly restricted expression in a set of cells in hindbrain and spinal cord. No expression was observed elsewhere. This expression pattern may explain occasionally occurring neural symptoms caused by inactivating mutations in the nephrin gene in patients with congenital nephrotic syndrome.
cAMP Regulates Cell Proliferation and Cyst Formation in Autosomal Polycystic Kidney Disease Cells
Authors: HANAOKA KAZUSHIGE , GUGGINO WILLIAM B.
Published: April 2021

Both epithelial cell proliferation and fluid accumulation are responsible for cyst growth in autosomal dominant polycystic kidney disease (ADPKD). It was previously reported that the cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in cysts from ADPKD patients and suggested that cAMP-stimulated Cl- and fluid secretion occurs through CFTR. The purpose of this study was to investigate the role of cell proliferation in cyst formation in ADPKD and to explore further the role of fluid secretion in cyst growth. Primary cultures both of ADPKD epithelial cells and a mixed population of normal renal epithelial cells isolated from the cortex (HRCE cells) were used. This study tested whether cAMP was involved both in stimulating cell proliferation and formation of cysts in vitro. 3H-Thymidine incorporation assays showed that epidermal growth factor stimulated proliferation both in ADPKD cells and HRCE cells. In addition, cAMP stimulated DNA synthesis and cell proliferation in ADPKD, but not HRCE, cells. The effects of cAMP and epidermal growth factor on cell growth in ADPKD cells were additive. cAMP also stimulated cyst enlargement and fluid secretion in ADPKD cells. By contrast, cyst formation and enlargement from HRCE cells occurred without cAMP. Fluid secretion into the cyst lumen was blocked by diphenylamine carboxylic acid (DPC) and glibenclamide in ADPKD cells but blocked only by DPC in HRCE cells. This study showed that ADPKD cells have unique characteristics; cAMP stimulates fluid secretion and cell proliferation, indicating cAMP plays a very important role in cyst growth during the course of ADPKD.
Proapoptotic Fas Ligand Is Expressed by Normal Kidney Tubular Epithelium and Injured Glomeruli
Authors: LORZ CORINA , ORTIZ ALBERTO , JUSTO PILAR , GONZÁLEZ-CUADRADO SILVIA , DUQUE NATALIA , GÓMEZ-GUERRERO CARMEN , EGIDO JESÚS
Published: April 2021

Fas ligand (FasL) is a cell membrane cytokine that can promote apoptosis through activation of Fas receptors. Fas receptor activation induces glomerular cell apoptosis in vivo and participates in tubular cell death during acute renal failure. However, there is little information on the expression of FasL in the kidney. This study reports that FasL mRNA and protein are present in normal mouse and rat kidney. In situ hybridization and immunohistochemistry showed that proximal tubular epithelium is the main site of FasL expression in the normal kidney. In addition, increased total kidney FasL mRNA and de novo FasL protein expression by glomerular cells were observed in two different models of glomerular injury: rat immune-complex proliferative glumerulonephritis and murine lupus nephritis. Both full-length and soluble FasL were increased in the kidneys of the mice with nephritis. Cultured murine proximal tubular epithelial MCT cells and primary cultures of murine tubular epithelial cells expressed FasL mRNA and protein. Tubular epithelium-derived FasL induced apoptosis in Fassensitive lymphoid cell lines but not in Fas-resistant lymphoid cell lines. By contrast, MCT cells grown in the presence of the survival factors of serum were resistant to FasL, and only became partially sensitive to apoptosis induced by high concentrations (100 ng/ml) of FasL upon serum deprivation. However, MCT cells stimulated with inflammatory mediators (tumor necrosis factor-α, interferon-γ, and lipopolysaccharide) increased cell surface Fas expression and were sensitized to apoptosis induced by FasL (FasL 55 ± 5% versus control 8.3 ± 4.1% apoptotic cells at 24 h, P < 0.05). Cytokine-primed primary cultures of tubular epithelial cells also acquired sensitivity to FasL-induced apoptosis. These results suggest that FasL expression by intrinsic renal cells may play a role in cell homeostasis in the normal kidney and during renal injury.
Increases in Serum Leptin Levels during Peritoneal Dialysis Are Associated with Inflammation and a Decrease in Lean Body Mass
Authors: STENVINKEL PETER , LINDHOLM BENGT , LO[Combining Diaeresis]NNQVIST FREDRIK , KATZARSKI KRASSIMIR , HEIMBU[Combining Diaeresis]RGER OLOF
Published: April 2021

Leptin, secreted from fat cells, functions as a lipostat mechanism through modulation of satiety signals. Markedly elevated leptin levels have been documented in uremic patients, especially in those who are treated by peritoneal dialysis (PD). However, the role of hyperleptinemia in uremic patients is not clear, and it is not known whether elevated leptin levels contribute to uremic anorexia and changes in body composition. In this prospective study, serum leptin, C-reactive protein (CRP), plasma insulin, and body composition (dual-energy x-ray absorptiometry) were measured in 36 patients (53 ± 1 yr) close to start and after about 1 yr of PD. In addition, markers of dialysis adequacy and urea kinetics were followed during treatment with PD. During PD, the total body fat mass (20.5 ± 1.0 to 22.9 ± 1.3 kg; P < 0.01), truncal fat mass (11.5 ± 0.7 to 13.2 ± 0.9 kg; P < 0.001), and serum leptin levels (20.1 ± 3.8 to 35.6 ± 6.8 ng/ml; P < 0.01) increased markedly, especially in patients with diabetes mellitus. Twenty-five PD patients that lost lean body mass during PD had significantly (P < 0.05) elevated initial CRP levels (14 ± 2 mg/L) compared to 11 patients (<10 mg/L) who gained lean body mass during PD. A significant increase in serum leptin levels (20.9 ± 4.2 to 42.7 ± 4.0 ng/ml; P < 0.001) was observed in those patients who lost lean body mass, whereas no such change (18.4 ± 8.4 to 19.2 ± 6.4 ng/ml) was observed in the patients that gained lean body mass during PD treatment. The present longitudinal results demonstrate that serum leptin level and body fat content increase markedly during PD, especially in diabetic patients. Patients that lost lean body mass during PD had higher initial CRP levels and increased their serum leptin levels significantly during PD compared to those patients that gained lean body mass. Additional studies are therefore needed to elucidate the role of hyperleptinemia and inflammation in causing anorexia, protein-malnutrition, and changes in body composition during treatment with PD.
Endothelium-Dependent Relaxation of Small Resistance Vessels Is Impaired in Patients with Autosomal Dominant Polycystic Kidney Disease
Authors: WANG DAN , IVERSEN JENS , STRANDGAARD SVEND
Published: April 2021

Impaired endothelium-dependent relaxation has been demonstrated previously in resistance vessels of Han:SPRD polycystic kidney disease rats. The aim of the present study was to investigate whether endothelium-dependent relaxation is reduced also in patients with autosomal dominant polycystic kidney disease (ADPKD) and whether this is influenced by the nitric oxide (NO) system. Small subcutaneous resistance vessels from normotensive ADPKD patients with normal or near-normal renal function (n = 9) and from healthy control subjects (n = 10) were mounted in a Mulvany-Halpern myograph. The morphology of the vessels and acetylcholine (ACh)-induced endothelium-dependent relaxation, as well as 3-morpholino-sydnonimine (SIN-1, NO donor)-induced endothelium-independent relaxation were investigated. The results showed that: (1) there were no significant differences in morphologic parameters of resistance vessels between the two groups; (2) the maximal ACh-induced relaxation rate was decreased in ADPKD patients compared with control subjects (71.5 ± 12.1 versus 85.2 ± 8.7%, P < 0.01); (3) in the presence of L-arginine (a substrate of NO synthase), a left shift of the ACh dose-response curves was found in control subjects, but not in ADPKD patients; (4) in the presence of the N
G-nitro-L-arginine methyl ester (an inhibitor of NO synthase), a right shift of the ACh dose-response curve was found in control subjects, but not in ADPKD patients; and (5) endothelium-independent relaxation rate induced with SIN-1 was similar in patients and control subjects. In conclusion, endothelium-dependent relaxation was impaired in resistance vessels from patients with ADPKD. The reduced response of the vessels to both the substrate and inhibitor of NO synthase in ADPKD suggests that an impairment of NO synthase may be involved in the mechanism of endothelial dysfunction in ADPKD.
Metabolism Alters the Selectivity of Angiotensin-(1-7) Receptor Ligands for Angiotensin Receptors
Authors: HANDA RAJASH K.
Published: April 2021

The present study examined whether metabolism of the putative angiotensin-(1-7) receptor agonist and antagonist [angiotensin-(1-7) and D-alanine7 angiotensin-(1-7), respectively] altered their ability to interact with angiotensin AT1, AT2, and AT4 receptor subtypes. Both angiotensin-(1-7) and D-alanine7 angiotensin-(1-7) competed with low affinity for 125I-sarcosine1, isoleucine8 angiotensin II binding to AT1 and AT2 receptors in rat liver and adrenal medulla membranes, respectively, and competed with low affinity for 125I-angiotensin IV binding to AT4 receptors in bovine kidney epithelial cell membranes. In vitro renal metabolism of the angiotensin-(1-7) receptor ligands (incubating peptides with rat cortical tissue homogenates) had minimal influence on low-affinity binding to AT1 and AT2 receptors, yet caused a significant and dramatic shift toward high-affinity binding for AT4 receptors. Low-affinity angiotensin II binding to the AT4 receptor was also shifted toward high-affinity binding following renal metabolism of the peptide. Conversely, angiotensins with high affinity for the AT4 receptor (e.g., angiotensin IV) were shifted toward low-affinity binding states following peptide metabolism. Incubation of 125I-angiotensin-(1-7) with rat cortical tissue generated the high-affinity AT4 receptor ligand 125I-angiotensin-(3-7), whereas the renal metabolism of 125I-angiotensin II generated both 125I-angiotensin-(3-7) and 125I-angiotensin IV. These results reveal that renal metabolism of angiotensin-(1-7) receptor ligands and angiotensin II yields products that have high affinity for the AT4 receptor and could potentially contribute to the biologic actions of the parent peptide in the kidney.
Gastrin Releasing Peptide-Preferring Bombesin Receptors Mediate Growth of Human Renal Cell Carcinoma
Authors: PANSKY ANDREAS , DE WEERTH ANDREAS , FASLER-KAN ELIZAVETA , BOULAY JEAN-LOUIS , SCHULZ MARTINA , KETTERER SYLVIA , SELCK CRISTIN , BEGLINGER CHRISTOPH , VON SCHRENCK TAMMO , HILDEBRAND PIUS
Published: April 2021

Bombesin-like peptides typically act as neurotransmitters along the brain-gut axis and as growth factors in various human tissues. The present study demonstrates the expression of gastrin releasing peptide (GRP)-preferring bombesin receptors in human renal cell carcinoma but not in normal kidney tissue. The expression of GRP receptors was characterized at the mRNA level by reverse transcription-PCR, as well as at the protein level by binding of 125I-[Tyr4] bombesin to membranes prepared from tumor tissue (K
d 0.3 nM) and healthy kidney tissue from the same four patients. GRP receptors were also demonstrated in four human kidney carcinoma cell lines (A-498, CAKI-1, CAKI-2, and ACHN). The effects of bombesin/GRP agonists and/or antagonists on growth were investigated in vitro on CAKI-2 cells, which expressed large amounts of GRP receptors. Cell numbers stimulated by 10% fetal calf serum were significantly stimulated by interleukin-1β (control) and GRP-7 (10-7 M), both in the range of 136 to 148%; addition of the GRP receptor antagonist acetyl-GRP(20-27) (10-6 M) completely reversed this effect. Bombesin alone (10-6 M) significantly stimulated CAKI-2 cells (129%) cultured with 0.5% fetal calf serum, whereas another antagonist, D-Phe6,Leu13,(CH2NH)Leu14 bombesin(6-14) (1 μM), alone did not inhibit growth, thus excluding an autocrine mechanism. These results indicate for the first time that malignant transformation of human kidney tissue into renal cell carcinoma is accompanied by novel expression of GRP receptors. Bombesin-like peptides might act as mitogens in these carcinomas, and they might be useful as diagnostic or therapeutic tools such as tumor imaging or internal radiotherapy.
Mutations in the Chloride Channel Gene CLCNKB as a Cause of Classic Bartter Syndrome
Authors: KONRAD MARTIN , VOLLMER MARTIN , LEMMINK HENNY H. , VAN DEN HEUVEL LAMBERTUS P. W. J. , JECK NIKOLA , VARGAS-POUSSOU ROSA , LAKINGS ALICIA , RUF RAINER , DESCHE[Combining Circumflex Accent]NES GEORGES , ANTIGNAC CORINNE , GUAY-WOODFORD LISA , KNOERS NINE V. A. M. , SEYBERTH HANNSJO[Combining Diaeresis]RG W. , FELDMANN DELPHINE , HILDEBRANDT FRIEDHELM
Published: April 2021

Inherited hypokalemic renal tubulopathies are differentiated into at least three clinical subtypes: (1) the Gitelman variant of Bartter syndrome (GS); (2) hyperprostaglandin E syndrome, the antenatal variant of Bartter syndrome (HPS/aBS); and (3) the classic Bartter syndrome (cBS). Hypokalemic metabolic alkalosis and renal salt wasting are the common characteristics of all three subtypes. Hypocalciuria and hypomagnesemia are specific clinical features of Gitelman syndrome, while HPS/aBS is a life-threatening disorder of the newborn with polyhydramnios, premature delivery, hyposthenuria, and nephrocalcinosis. The Gitelman variant is uniformly caused by mutations in the gene for the thiazide-sensitive NaCl-cotransporter NCCT (SLC12A3) of the distal tubule, while HPS/aBS is caused by mutations in the gene for either the furosemide-sensitive NaK-2Cl-cotransporter NKCC2 (SLC12A1) or the inwardly rectifying potassium channel ROMK (KCNJ1). Recently, mutations in a basolateral chloride channel CLC-Kb (CLCNKB) have been described in a subset of patients with a Bartter-like phenotype typically lacking nephrocalcinosis. In this study, the screening for CLCNKB mutations showed 20 different mutations in the affected children from 30 families. The clinical characterization revealed a highly variable phenotype ranging from episodes of severe volume depletion and hypokalemia during the neonatal period to almost asymptomatic patients diagnosed during adolescence. This study adds 16 novel mutations to the nine already described, providing further evidence that mutations in the gene for the basolateral chloride channel CLC-Kb are the molecular basis of classic Bartter syndrome. Interestingly, the phenotype elicited by CLCNKB mutations occasionally includes HPS/aBS, as well as a Gitelman-like phenotype.
Retinoic Acid Reduces Glomerular Injury in a Rat Model of Glomerular Damage
Authors: WAGNER JU[Combining Diaeresis]RGEN , DECHOW CLAUDIUS , MORATH CHRISTIAN , LEHRKE INGO , AMANN KERSTIN , WALDHERR RU[Combining Diaeresis]DIGER , FLOEGE JU[Combining Diaeresis]RGEN , RITZ EBERHARD
Published: April 2021

In the reaction of kidneys to injury, cytokine-driven proliferation plays an important role and precedes the development of glomerulosclerosis. There is great interest in agents that may interfere with such proliferation. Therefore, a rat model of mesangioproliferative glomerulonephritis (induced by anti-Thy1.1) was studied, and the effects of all-trans-retinoic acid (all-trans-RA) and isotretinoin, powerful antiproliferative and anti-inflammatory substances, on glomerular damage and cell proliferation were examined. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans-RA or 40 mg/kg body wt isotretinoin (n = 9 to 11 per group), using either a pretreatment (days -2 through 8) or posttreatment (days +3 through +8) protocol, i.e., starting before or after the induction of anti-Thy1.1 nephritis, respectively. All-trans-RA prevented the BP increase evoked by anti-Thy1.1 (anti-Thy1.1/vehicle, 112.2 ± 4.8 mmHg; anti-Thy1.1/RA, 87.5 ± 2.5 mmHg; P < 0.001). Treatment with all-trans-RA or isotretinoin produced a 70% decrease in the urinary albumin excretion rate (P < 0.02). Periodic acid-Schiff staining of saline-perfused kidneys (day 8) revealed significantly fewer glomerular cells in RA-treated nephritic rats (anti-Thy1.1/vehicle, 97 ± 3.1 cells/glomerulus; anti-Thy1.1/RA, 80 ± 4.4; P < 0.02; control/vehicle, 69 ± 1.2). No difference was observed between all-trans-RA and isotretinoin treatment. The capillary occlusion scores were significantly lower for the anti-Thy1.1/RA-treated group (1.9 ± 0.1) than for the anti-Thy1.1/vehicle-treated group (2.9 ± 0.5, P < 0.001). In the anti-Thy1.1/vehicle-treated group, 11.9 ± 1.1 glomerular cells were proliferating cell nuclear antigen-positive; however, in the anti-Thy1.1/RA-treated group, only 5.3 ± 0.8 cells were proliferating cell nuclear antigen-positive (P < 0.002; control, 2.2 ± 0.2). Glomerular mitoses were reduced by 67% in the anti-Thy1.1/RA-treated group, compared with the anti-Thy1.1/control group (P < 0.002). Glomerular staining for platelet-derived growth factor B-chain was significantly reduced in anti-Thy1.1-treated nephritic rats in the presence of isotretinoin or all-trans-RA, compared with the vehicle-treated group (P < 0.001). It is concluded that all-trans-RA limits glomerular proliferation, glomerular lesions, and albuminuria in an established model of renal damage. The findings point to retinoids as potential novel modulators of glomerular injury.
Quantification and Longitudinal Trends of Kidney, Renal Cyst, and Renal Parenchyma Volumes in Autosomal Dominant Polycystic Kidney Disease
Authors: KING BERNARD F. , REED JUDD E. , BERGSTRALH ERIK J. , SHEEDY PATRICK F. , TORRES VICENTE E.
Published: April 2021

The aims of this study were to assess the accuracy and reproducibility of volumetric determinations of total kidney, renal cyst, and renal parenchymal volumes, using fast electron-beam computerized tomography scanning, and to determine the rate of change of these volumes. Nine patients with autosomal dominant polycystic kidney disease (ADPKD) and serum creatinine ≤ 1.3 mg/dl and/or an initial iothalamate clearance ≥ to 60 ml/min per 1.73 m2 were imaged weekly over a 3-wk period (total of 3 times). Approximately 8 yr later, they returned for follow-up studies. The kidney volume estimation technique involved a manual segmentation (perimeter drawing) of the kidneys and a semiautomatic threshold approach, using a histogram analysis of the peak densities of renal parenchyma and renal cysts. At entry, total kidney and renal cyst volumes correlated positively with age, while renal parenchymal volumes and GFR correlated negatively with age. The average coefficient of variation values for the three initial consecutive measurements of total kidney, renal cyst (actual and as a percent of total volume), and renal parenchymal volume were 3.4, 7.2, 5.3, and 5.6%, respectively. During the 8 yr of follow-up, total kidney and renal cyst volumes increased, while renal parenchymal volumes and GFR declined. The rate of increase in total kidney and renal cyst volumes varied markedly from patient to patient. There was a significant correlation between rate of increase in renal cyst volume and the rate of decline in GFR. The patients with an initial urine protein/osmolality ratio >0.13 mg/L per mosmol per kg had a significantly higher increase in renal volume and decline in GFR than those with a lower ratio. In summary, the results of this pilot study suggest that: (1) electron-beam computerized tomography is capable of measuring total kidney, renal cyst, and renal parenchymal volumes reproducibly; (2) total kidney and renal cyst volumes increase, while parenchymal volumes decrease with time; (3) the increase in cyst volume correlates best with the decline in renal function; and (4) renal volumes appear to be good surrogate markers for disease progression in ADPKD.
Energy Transfer Is the Single Most Important Factor for the Difference in Vascular Response between Isolated Ultrafiltration and Hemodialysis
Authors: VAN DER SANDE FRANK M. , GLADZIWA ULRICH , KOOMAN JEROEN P. , BO[Combining Diaeresis]CKER GEORGE , LEUNISSEN KAREL M. L.
Published: April 2021

Differences in vascular reactivity between isolated ultrafiltration (i-UF) and hemodialysis (UF + HD) have been attributed to various factors, including differences in core temperature (CT) and energy transfer (ET). However, the relative importance of these thermal factors is not known. The aim of this study was to elucidate to what extent differences in ET are responsible for the divergent vascular response between i-UF and UF + HD. During four different dialysis treatments in 15 patients, four measurements were performed that consisted of 1 h of i-UF, UF + HD at a dialysate temperature (T
d) of 37.5°C (UF + HD37.5), UF + HD at T
d 35.5°C (UF + HD35.5), and UF + HD with a similar ET as during i-UF(UF + HDET-set). The UF rate in all sessions was 1 L/h. CT (°C) decreased significantly during i-UF and UF + HDET-set (P < 0.05), increased significantly during UF + HD37.5 (P < 0.05), and remained unchanged during UF + HD35.5 (NS). Forearm vascular reactivity increased significantly during i-UF, UF + HDET-set, and UF + HD35.5 (P < 0.05), but not during UF + HD37.5 (NS). Venous tone increased significantly during i-UF, UF + HD35.5, and UF + HDET-set (P < 0.05), and decreased significantly during UF + HD37.5 (P < 0.05). When i-UF and UF + HD are matched for ET, all differences in vascular response disappear, showing that differences in ET are the single most important factor for the observed difference in vascular response between i-UF and UF + HD. In contrast to UF + HD37.5, vascular reactivity was improved when the increase in CT was prevented during UF + HD35.5 and appeared to increase more when CT was lowered. Preventing the increase in CT during UF + HD appears to be mandatory for optimization of hemodynamic stability during dialysis.
A New Anti-Inflammatory Compound, FR167653, Ameliorates Crescentic Glomerulonephritis in Wistar-Kyoto Rats
Authors: WADA TAKASHI , FURUICHI KENGO , SAKAI NORIHIKO , IWATA YASUNORI , YOSHIMOTO KEIICHI , SHIMIZU MIHO , KOBAYASHI KEN-ICHI , MUKAIDA NAOFUMI , MATSUSHIMA KOUJI , YOKOYAMA HITOSHI
Published: April 2021

The pathophysiologic effects of FR167653 were investigated in a model of crescentic glomerulonephritis induced by a small dose of nephrotoxic serum in Wistar-Kyoto rats. The rats developed crescentic glomerulonephritis by 6 d after the administration of serum. The subcutaneous administration of FR167653 (32 mg/kg) markedly decreased the severity of the renal damage. In a group of rats treated with FR167653 daily from day 0 to day 6, glomerular damage, including crescent formation and proteinuria, was virtually absent. FR167653 markedly decreased urinary levels of monocyte chemoattractant protein-1 (MCP-1). In addition, FR167653 reduced production of MCP-1 protein and transcripts in the diseased kidneys. In a group of rats for which treatment was initiated on day 3, shortly after the appearance of glomerular abnormalities, the progression of renal disease was appreciably retarded, with partial inhibition of MCP-1. In contrast, when rats were treated only on the first day, no beneficial effects were observed and severe proliferative and necrotizing glomerulonephritis, with crescent formation, was induced by day 6, with the upregulation of MCP-1. These results suggest that FR167653 may be effective against crescentic glomerulonephritis, possibly via the inhibition of MCP-1. In addition, there was marked reduction in renal injury even when FR167653 treatment was initiated after glomerular inflammation was established, suggesting that the therapeutic application of FR167653 may be clinically useful for human renal diseases.
ÖĞRETİM ELEMANLARININ SINIF YÖNETİM MODELLERİNE İLİŞKİN ÖĞRENCİ ALGISI ÖLÇEĞİNİN GEÇERLİK GÜVENİRLİK ÇALIŞMASI
Authors: Ugurlu Celal Teyyar , Bozpolat Ebru , Usta Gonca , Şimşek Ahmet Salih
Published: April 2021

Bu araştırmanın amacı; üniversite öğrencilerinin öğretim elemanlarının sınıf yönetimi becerilerine ilişkin algılarını ortaya koymak için geçerliği ve güvenirliği kanıtlanmış bir ölçme aracının geliştirilmesidir. Bu amaçla, aşamalı örnekleme yöntemiyle Cumhuriyet Üniversitesinde farklı fakültelerde yer alan öğrenciler tesadüfi örnekleme yönteminden yararlanılarak belirlenmiştir. Araştırma kapsamında toplam 850 öğrenciye veri toplama aracı uygulanmış, ancak toplanan ölçeklerden eksik doldurulanlar çıkarılarak 814 öğrenciye ulaşılmıştır. Ölçek geliştirme sürecinde ön uygulama için oluşturulan formla, 145 üniversite öğrencisi üzerinden elde edilen veriler analiz edilmiştir. Ön uygulama ile elde edilen verilere AFA yapılmış ve öncelikle maddelerin faktör yükleri dikkate alınmıştır. Böylece, esas uygulama 29 madde ve üç bileşenli bir yapı ile gerçekleştirilmiştir. Esas uygulamadan elde edilen verilere AFA ve DFA yapılmıştır. Yapılan analizler sonucunda ölçek 24 madde ve üç bileşenden oluşan bir yapı olarak son halini almıştır. Ölçek geliştirmeye ilişkin tüm bulgular birlikte değerlendirildiğinde SYBAÖ’nin öğretim elemanlarının sınıf yönetim becerilerini ölçmede kullanılabilecek geçerli ve güvenilir bir ölçek olduğu söylenebilir.
ÖRGÜTLERİN SEMBOLİK ROLLERİNE İLİŞKİN KAVRAMLARIN İNCELENMESİ
Authors: Hatipoğlu Gizem , Nayir Funda
Published: April 2021

Örgütler varlıklarını sürdürebilmek için dış dünyaya ihtiyaç duymaktadır. Dış dünyaya yansıttıkları olumlu sinyaller örgütlerin tercih edilmeleri açısından önemli görülmektedir. Bu sebeple dış görünüşlerine dikkat etmektedirler. Bu dış görünüşleri ile alakalı literatürde karşımıza örgütsel saygınlık, örgütsel imaj, örgütsel kimlik ve örgütsel itibar kavramları çıkmaktadır. Ancak, örgütsel literatürde yer alan örgütsel saygınlık, örgütsel imaj, örgütsel kimlik ve örgütsel itibar kavramlarının araştırmalarda kullanımlarında teorik olarak bir tutarlılık olmadı, birbirinin yerine veya eş anlamlı olarak kullanımları dikkat çekmektedir. Bu sebeple bu çalışmanın amacı, örgüt literatüründe kullanılan bu kavramların teorik çerçevesinin oluşturulması ve bu kavramların tanımlarında veya kullanımındaki yanlışlıkların düzeltilmesi için araştırmacılara yol göstermek olarak belirlenmiştir. Bu araştırmada; örgütsel saygınlık, örgütsel imaj, örgütsel kimlik ve örgütsel itibar kavramları hakkında terminolojik tanımlara, yapılmış olan çalışmaları sentezleyerek aktarımlarına yer verilmektedir. Böylelikle literatürde yer alan yanlış veya yerine kullanımların önüne geçilmesi hedeflenmiştir.
HAN HANEDANLIĞININ SAVAŞÇI İMPARATORU: HAN WU DI 汉武帝
Authors: Kalkır Nurcan
Published: April 2021

Bu makalenin konusu Han Hanedanlığı döneminin (M.Ö.206-M.S.220) yedinci İmparatoru Han Wu Di’nin politikaları ve Hunlarla mücadelesidir. Amacı, Wu Di’nin siyasi, askeri, ekonomik politikalarına, onun döneminde yaşanan Hun-Çin savaşlarına ve iki devlet arasında değişen ilişkilere ışık tutmaktır. Çalışmada birincil tarih kaynakları kullanılmıştır. Araştırma, Wu Di’nin klasik Çin tarih kayıtlarındaki biyografileri taranarak gerçekleştirilmiştir. Wu Di, siyaset, askeri örgütlenme, bürokrasi ve ekonomi alanlarında köklü reformlar yapmıştır. Ayrıca Konfüçyüs öğretileri doğrultusunda gerçekleştirdiği uygulamalarla dikkat çekmiştir. Wu Di’nin hüküm sürdüğü döneme damgasını vuran bir diğer olgu ise Hun-Çin ilişkilerinde yaşanan değişimdir. Han Hanedanlığının kurulduğu yıllarda Çin siyasi, askeri ve ekonomik alanlarda oldukça zayıf bir durumdadır. Hunlar ise Mo Dun liderliğinde hızla güçlenmektedir. Hunlar sık sık Çin topraklarında yağmalar yapmaktadır. Bazen ise bu yağmalar kuşatmalara kadar gitmiş ve her seferinde ardından barış anlaşmaları yapılmıştır. Han Wu Di döneminde bu barış antlaşmaları son bulmuştur. Çin için sürekli bir tehdit unsuru sayılan Hunlarla olan ilişkiler farklı bir boyut kazanmış ve iki devlet tarihinde de büyük ölçüde önemli olan Hun-Çin savaşları yaşanmaya başlamıştır. Bu savaşlar sonucunda Hunlar Çin için ciddi bir tehdit olmaktan çıkmıştır. Wu Di, savaş yanlısı politikalarıyla Çin ve Türk tarihinin en etkili hükümdarlarından biri olmuştur.