bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Relevance of Activated β1 Integrins in Mercury-Induced Nephritis
Authors: ESCUDERO ESTHER , MARTÍN ANA , NIETO MARTA , NIETO ELENA , NAVARRO ELENA , LUQUE ALFONSO , CABAN[Combining Tilde]AS CARLOS , SÁNCHEZ-MADRID FRANCISCO , MAMPASO FRANCISCO
Published: April 2021

Cell adhesion through different adhesion molecules is a crucial event in the inflammatory response. Integrins can only bind and mediate cellular adhesion after their activation by different specific stimuli. The state of β1 integrin activation can be assessed by a group of monoclonal antibodies (HUTS) that selectively recognize β1 integrins in their active form. A similar activated epitope in the rat was defined using the anti-human monoclonal antibody HUTS-21, which recognizes an activation-dependent epitope on the β1 chain. It was found that the divalent cations Mn2+ and Hg2+ were able to induce in vitro the activation of β1 integrins on rat lymphocytes. The Hg2+ cation induces an autoimmune disease in the Brown Norway rat characterized by synthesis and glomerular deposits of anti-glomerular basement membrane antibodies, proteinuria, and interstitial nephritis. Using the mercury model of nephritis, it was found that the expression of HUTS-21 epitope is induced in vivo in rat lymphocytes, and its appearance is correlated with the other parameters at the onset of the disease. In addition, the administration of HUTS-21 monoclonal antibody to HgCl2-treated rats offered evidence of its protective effects (1) against infiltration of renal interstitium by leukocytes, and (2) in the reduction of anti-glomerular basement membrane synthesis and glomerular deposition. Nevertheless, urinary protein values remained unaffected. These results demonstrate a key role of β1-activated integrins in both leukocyte cell-cell interactions and leukocyte infiltration pathway mechanism, and also indicate that leukocyte migration may have less importance in the development of this disease than previously thought.
Pharmacokinetics of Once Daily Intraperitoneal Cefazolin in Continuous Ambulatory Peritoneal Dialysis Patients
Authors: LOW CHAI LUAN , GOPALAKRISHNA KAMANI , LYE WAI CHOONG
Published: April 2021

This study determined the pharmacokinetic characteristics of once daily intraperitoneal (IP) cefazolin in continuous ambulatory peritoneal dialysis (CAPD) patients. Each of the 10 volunteer CAPD patients without active peritonitis received a single IP dose of 1 g of cefazolin sodium for a 6-h dwell. All patients underwent a fixed CAPD regimen comprising a first 6-h dwell followed by two 3-h dwells and a final 12-h overnight dwell. Blood and dialysate samples were collected at 0, 0.5, 1, 2, 3, 6 (end of first dwell), and 24 h after the administration of IP cefazolin. Any urine produced was collected over the 24-h study period. A validated HPLC method was used to analyze cefazolin in plasma, dialysate, and urine. The bioavailability was found to be 77.9 ± 3.1%, volume of distribution 0.20 ± 0.05 L/kg, and plasma half-life 39.9 ± 25.4 h. Mean total, renal, and peritoneal clearances were 4.5 ± 2.3, 1.4 ± 1.1, and 3.5 ± 1.8 ml/min, respectively. Mean plasma and dialysate concentrations at 24 h were 42.8 ± 14.3 and 31.8 ± 11.7 mcg/ml, respectively, well above the minimum inhibitory concentrations (MIC) of susceptible organisms. A once daily IP cefazolin dose of 500 mg/L gave desirable pharmacokinetic attributes for use as a suitable alternative to vancomycin for empiric treatment of CAPD-associated peritonitis.
Encrusted Pyelitis of Native Kidneys
Authors: HERTIG ALEXANDRE , DUVIC CHRISTIAN , CHRETIEN YVES , JUNGERS PAUL , GRU[Combining Diaeresis]NFELD JEAN-PIERRE , RIEU PHILIPPE
Published: April 2021

This study reports the first four cases of encrusted pyelitis involving native kidneys. The clinical features, management, and outcome of these patients were analyzed. Predisposing factors were underlying urologic disease and/or urologic manipulations, debilitating diseases, hospitalization, and prolonged antibiotic therapies. Presenting symptoms were renal failure in three patients with ureteroileal urinary diversion and manifestations of cystitis in one patient. Computed tomography scan of the urinary tract was critical for diagnosis. Presence of struvite was demonstrated by crystalluria and infrared spectrophotometry analysis of the encrusted material. Corynebacterium urealyticum urinary infection was identified in one case. Surgery (one patient) and palliative ureteral diversion (one patient), respectively, led to death and end-stage renal failure. Successful dissolution of encrusted pyelitis was obtained in two patients treated with intravenous vancomycin and local acidification of the renal collecting system. Clinical observation shows that encrusted pyelitis is a threatening disorder that destroys the native kidneys and may lead to end-stage renal failure. Successful treatment of the disease by chemolysis and antibiotics depends on correct and early diagnosis. Diagnosis required recognition of the predisposing factors, computed tomography imaging of the urinary tract, crystalluria, and identification of urea-splitting bacteria with prolonged culture on selective medium.
Effect of Elevated Glucose on Endothelin-Induced Store-Operated and Non-Store-Operated Calcium Influx in Renal Mesangial Cells
Authors: NUTT LETA K. , O'NEIL ROGER G.
Published: April 2021

Early diabetic nephropathy exhibits renal glomerular hyperfiltration and an increase in renal plasma flow. The hyperfiltration is a dysfunctional state that may arise from a hyperglycemic-induced hypocontractility of glomerular mesangial cells that may be associated with depressed Ca2+ signaling events. The present study was designed to determine the effects of acute (minutes) and chronic (days) elevated glucose levels on endothelin-induced calcium signaling with a particular emphasis on the potential influence on stores and store-operated Ca2+ influx (SOCI; also called capacitative calcium entry) in glomerular mesangial cells. Primary cultures of rat mesangial cells were grown in either high (30 mM) or normal (5 mM) glucose-containing media and tested in the presence of either high (30 mM) or normal (5 mM) glucose levels. Intracellular calcium levels were monitored with the calcium-sensitive fluorophore fura-2 before and after treatment with either endothelin-1 (10 nM), to induce typical Ca2+ signals, or the endoplasmic reticulum (ER) Ca-ATPase inhibitor thapsagargin (1 μM), to unload ER Ca2+ stores. Both acute and chronic exposure to high glucose levels depressed the endothelin-induced calcium signal. However, neither release of Ca2+ from stores nor SOCI were depressed by high glucose levels. In contrast, an endothelin-induced calcium entry pathway (likely receptor-operated calcium influx), separate from SOCI, was markedly depressed in the presence of both acute and chronic high glucose levels. The depressant effect of high glucose was rapidly (minutes) reversible upon returning to normal glucose levels. It is concluded that high glucose levels depress endothelin-induced calcium signaling in rat mesangial cells by inhibiting non-SOCI Ca2+ entry pathways, namely the receptor-operated Ca2+ influx pathway. The glucose-induced alterations in the receptor-operated calcium influx pathway may, in part, contribute to the depressed contractile state of glomerular cells during periods of hyperglycemia.
In Vivo Administration of a Nuclear Transcription Factor-κB Decoy Suppresses Experimental Crescentic Glomerulonephritis
Authors: TOMITA NARUYA , MORISHITA RYUICHI , LAN HUI Y. , YAMAMOTO KEI , HASHIZUME MASAHIDE , NOTAKE MITSUE , TOYOSAWA KAORU , FUJITANI BUICHI , MU WEI , NIKOLIC-PATERSON DAVID J. , ATKINS ROBERT C. , KANEDA YASUFUMI , HIGAKI JITSUO , OGIHARA TOSHIO
Published: April 2021

Glomerular expression of cytokines, interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α), together with leukocytic infiltration, are prominent features in crescentic glomerulonephritis. Because these cytokines are targets for nuclear transcription factor-κB (NF-κB), the use of NF-κB decoy oligodeoxynucleotide (ODN) treatment was evaluated in an experimental disease model. Crescentic glomerulonephritis was induced in primed Wistar rats by injection of sheep antiglomerular basement membrane serum. Thirty minutes after injection, rats were anesthetized and the left kidney was perfused with NF-κB decoy ODN or scrambled ODN control mixed with a virus-liposome complex, and then killed 7 d later. Animals given the scrambled control ODN developed severe glomerulonephritis by day 7 with heavy proteinuria, glomerular crescents and interstitial lesions, marked leukocytic infiltration, and upregulated renal expression of cytokines (IL-1 and TNF-α) and adhesion molecules (intercellular adhesion molecule-1). In contrast, NF-κB decoy ODN treatment substantially inhibited the disease with a 50% reduction in proteinuria, a threefold reduction in histologic damage, a 50% reduction in leukocytic infiltration, and a 50 to 80% reduction in the renal expression of cytokines and leukocyte adhesion molecules. In conclusion, this study has demonstrated that NF-κB plays a key role in cytokine-mediated renal injury and that NF-κB decoy ODN treatment has clear therapeutic potential in rapidly progressive glomerulonephritis.
Quantitative Trait Loci Modulate Renal Cystic Disease Severity in the Mouse bpk Model
Authors: GUAY-WOODFORD LISA M. , WRIGHT CHRISTOPHER J. , WALZ GERD , CHURCHILL GARY A.
Published: April 2021

Numerous mouse models of polycystic kidney disease (PKD) have been described in which the mutant phenotypes closely resemble human PKD with regard to morphology, cyst localization, and disease progression. As in human PKD, genetic background affects the disease phenotype in mouse PKD models. Using experimental crosses, these modifying effects can be dissected into discrete genetic factors referred to as quantitative trait loci. The locus for the mouse bpk model was recently mapped to chromosome (Chr) 10. In the course of these studies, marked variability was observed in the renal cystic disease expressed in F2 bpk/bpk homozygotes of a (BALB/c-+/bpk × CAST/Ei)F1 intercross. The current study was undertaken to further characterize the renal cystic disease as quantitative trait in this F2 cohort and to map the genetic modifiers that modulate this phenotype. Whole-genome scans revealed a CAST-derived locus on distal Chr 6, near D6Mit14, that affects renal cystic disease severity. Additional analyses identified loci on Chr 1, Chr 2, and Chr 4, as well as a possible interaction between the Chr 6 locus and a locus on distal Chr 1, near D1Mit17. Interestingly, the gene encoding RGS7, a regulator of G protein signaling that binds to polycystin-1, was mapped to the same Chr 1 interval. It is concluded that the severity of the bpk renal cystic disease phenotype is modulated by multiple loci and possibly by epistatic interaction among them. It is hypothesized that the gene encoding the polycystin-binding partner RGS7 is a candidate for the Chr 1 genetic modifier.
Contribution of Angiotensin II to Late Renal Injury after Acute Ischemia
Authors: PAGTALUNAN MARIA ENRICA , OLSON JEAN L. , MEYER TIMOTHY W.
Published: April 2021

Rats recovering from acute renal ischemia exhibit tubule loss and interstitial fibrosis followed by development of proteinuria and glomerular sclerosis. The current study assessed the contribution of angiotensin II (AngII) to these processes. The contribution of AngII to early tubule loss and interstitial fibrosis was assessed in rats studied for 35 d after right nephrectomy and transient occlusion of the left renal artery. One group of rats received no treatment, while a second group received losartan beginning at 2 d following ischemia. Studies at 35 d showed that losartan did not improve GFR (2.04 ± 0.30 ml/min treated, 2.16 ± 0.21 ml/min untreated), reduce the fraction of glomeruli that were no longer connected to normal tubule segments (42 ± 9% treated, 42 ± 13% untreated), or limit expansion of the interstitial volume fraction (25 ± 3% treated, 25 ± 4% untreated). The contribution of AngII to progressive glomerular injury following initial recovery from ischemia was assessed in similarly prepared rats studied for 140 d. One group of rats received no treatment, while a second group received enalapril beginning at 35 d following ischemia. Enalapril markedly reduced proteinuria (78 ± 17 mg/d treated, 229 ± 52 mg/d untreated) and the prevalence of segmental glomerular sclerosis (14 ± 9% treated, 45 ± 10% untreated). Untreated rats developed sclerotic lesions in glomeruli not connected to normal tubules, as well as in glomeruli connected to normal tubules. Enalapril prevented injury in both classes of glomeruli. These results indicate that AngII does not contribute to interstitial fibrosis during recovery from ischemic injury. Reduction of AngII activity, can, however, prevent secondary glomerular injury in kidneys initially damaged by ischemia.
Requirement of Cyclin D1 in Mesangial Cell Mitogenesis
Authors: LANG STEFAN , HARTNER ANDREA , STERZEL R. BERND , SCHO[Combining Diaeresis]CKLMANN HARALD O.
Published: April 2021

Hyperplasia of mesangial cells (MC) is a frequent finding in glomerulonephritis. The control and function of cyclin D1, a regulator of cell cycle progression, in MC proliferation in vivo and in vitro were investigated. In a rat model of mesangioproliferative glomerulonephritis, increases in the number of cyclin D1-positive MC nuclei were prominent on day 5 of the disease, preceding the peak of MC hyperplasia. In growth-arrested rat MC in culture, mitogenic stimulation with serum or platelet-derived growth factor (PDGF) led to rapid increases in cyclin D1 protein expression. Transforming growth factor-β1 inhibited PDGF induction of cyclin D1 protein at 12 h. In an examination of the subcellular distribution of cyclin D1, it was observed that stimulation of MC with PDGF for 6 h caused translocation of cyclin D1 from the cytoplasm into the nucleus. Coincubation with PDGF and transforming growth factor-β1 completely inhibited this effect, without altering the cellular cyclin D1 protein abundance at that time point. To test whether reduction of cyclin D1 protein levels was sufficient to inhibit mitogenesis, MC were transfected with antisense oligonucleotides (ODN) complementary to rat cyclin D1 mRNA. Antisense ODN against cyclin D1 reduced the serum- or PDGF-induced protein expression of cyclin D1 to 27 or 10% of control levels, respectively. These inhibitory effects were correlated with diminished cyclin-dependent kinase 4 activity. Antisense ODN against cyclin D1 also decreased the PDGF-induced increase in p21Waf-1 protein levels. The MC proliferation caused by serum or PDGF was markedly inhibited by antisense ODN against cyclin D1, as measured by [3H]thymidine uptake and cell counts. It is concluded that increased cyclin D1 protein expression of MC is required for MC proliferation. Targeting cyclin D1 expression may represent an effective means to inhibit MC proliferation in vitro and in vivo.
Strong and Selective Glomerular Localization of CD134 Ligand and TNF Receptor-1 in Proliferative Lupus Nephritis
Authors: ATEN JAN , ROOS ANJA , CLAESSEN NIKE , SCHILDER-TOL ESTHER J. M. , TEN BERGE INEKE J. M. , WEENING JAN J.
Published: April 2021

CD134 (OX40) is a member of the tumor necrosis factor (TNF) receptor (TNFR) family that can be expressed on activated T lymphocytes. Interaction between CD134 and its ligand (CD134L) is involved in costimulation of T and B lymphocyte activation, and in T cell adhesion to endothelium. To examine the possible role of this interaction in the pathogenesis of systemic lupus erythematosus (SLE), expression of CD134 and CD134L on peripheral blood leukocytes was studied, and no significant differences between SLE patients and control individuals were found. Immunohistology on renal biopsies from patients with lupus nephritis or other renal disorders, using a recombinant human CD134-containing chimeric molecule to detect CD134L, demonstrated the abundant presence of CD134L in all cases of proliferative lupus nephritis in a granular distribution predominantly along the epithelial side of the glomerular capillary wall. Confocal laser scanning microscopy indicated colocalization with subepithelial immune deposits. In none of the other renal disorders examined, including nonproliferative forms of lupus nephritis, was glomerular staining for CD134L detected in a similar pattern. Endothelial CD134L expression was frequently observed in different types of vasculitis. CD134 was detected on perivascular infiltrating leukocytes and on part of the tubular epithelium, but not on glomerular resident cells. Immunohistology for several other TNF(R) family members revealed in proliferative lupus nephritis a similar distribution for TNFR1 as was observed for CD134L. In contrast, glomerular expression of TNFR2 was similar in all cases examined. The glomerular presence of CD134L and TNFR1 in proliferative lupus nephritis in association with subepithelial immune deposits may be of pathogenetic significance and have diagnostic value.
Lithium Nephrotoxicity
Authors: MARKOWITZ GLEN S. , RADHAKRISHNAN JAI , KAMBHAM NEERAJA , VALERI ANTHONY M. , HINES WILLIAM H. , D'AGATI VIVETTE D.
Published: April 2021

This study examines the clinical features, pathologic findings, and outcome of 24 patients with biopsy-proven lithium toxicity. The patient population was 50% male, 87.5% Caucasian, and had a mean age of 42.5 yr (range, 26 to 57). Mean duration of lithium therapy for bipolar disorder was 13.6 yr (range, 2 to 25). All patients were biopsied for renal insufficiency (mean serum creatinine 2.8 mg/dl; range, 1.3 to 8.0), with associated proteinuria >1.0 g/d in 41.7%. Nephrotic proteinuria (>3.0 g/d) was present in 25%. Other features included nephrogenic diabetes insipidus in 87% and hypertension in 33.3%. Renal biopsy revealed a chronic tubulointerstitial nephropathy in 100%, with associated cortical and medullary tubular cysts (62.5%) or dilatation (33.3%). All of the renal cysts stained for epithelial membrane antigen, while 51.4% stained with lectin Arachis hypogaea, and only 3.8% stained with Tetragonolobus purpureas, indicating they originated from distal and collecting tubules. The degree of tubular atrophy and interstitial fibrosis was graded as severe in 58.3%, moderate in 37.5%, and mild in 4.2% of cases. There was a surprisingly high prevalence of focal segmental glomerulosclerosis (50%) and global glomerulosclerosis (100%), sometimes of equivalent severity to the chronic tubulointerstitial disease. The significant degree of foot process effacement (mean 34%, five of 14 cases with >50%) suggests a potential direct glomerular toxicity. Focal segmental glomerulosclerosis correlated with proteinuria >1.0 g/d (P = 0.0014, Fisher exact test). Despite discontinuation of lithium, seven of nine patients with initial serum creatinine values >2.5 mg/dl progressed to end-stage renal disease (ESRD). Only three patients, all with initial serum creatinine <2.1 mg/dl, had subsequent improvement in renal function. By Kaplan-Meier survival analysis, the only significant predictor of progression to ESRD was serum creatinine >2.5 mg/dl at biopsy (P = 0.008). In conclusion, lithium nephrotoxicity primarily targets distal and collecting tubules, with a higher incidence of proteinuria and associated glomerular pathology than recognized previously. Renal dysfunction is often irreversible despite lithium withdrawal, and early detection is essential to prevent progression to ESRD.
Characterization of Renal Chloride Channel (CLCN5) Mutations in Dent's Disease
Authors: YAMAMOTO KATSUSUKE , COX JEREMY P. D. T. , FRIEDRICH THOMAS , CHRISTIE PAUL T. , BALD MARTIN , HOUTMAN PETER N. , LAPSLEY MARTA J. , PATZER LUDWIG , TSIMARATOS MICHEL , VAN'T HOFF WILLIAM G , YAMAOKA KANJI , JENTSCH THOMAS J. , THAKKER RAJESH V.
Published: April 2021

Dent's disease is an X-linked renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and renal failure. The disease is caused by mutations in a renal chloride channel gene, CLCN5, which encodes a 746 amino acid protein (CLC-5), with 12 to 13 transmembrane domains. In this study, an additional six unrelated patients with Dent's disease were identified and investigated for CLCN5 mutations by DNA sequence analysis of the 11 coding exons of CLCN5. This revealed six mutations: four frameshift deletions involving codons 392, 394, 658, and 728, one nonsense mutation (Tyr617Stop), and an A to T transversion at codon 601 that would result in either a missense mutation (Asp601Val) or creation of a novel donor splice site. These mutations were confirmed by restriction endonuclease or sequence-specific oligonucleotide hybridization analysis and were not common polymorphisms. The frameshift deletions and nonsense mutation predict truncated and inactivated CLC-5. The effects of the putative missense Asp601Val mutant CLC-5 were assessed by heterologous expression in Xenopus oocytes, and this revealed a chloride conductance that was similar to that observed for wild-type CLC-5. However, an analysis of the mutant CLCN5 transcripts revealed utilization of the novel donor splice site, resulting in a truncated CLC-5. Thus, all of the six mutations are likely to result in truncated CLC-5 and a loss of function, and these findings expand the spectrum of CLCN5 mutations associated with Dent's disease.
Selective ETA Receptor Antagonism with ABT-627 Attenuates All Renal Effects of Endothelin in Humans
Authors: HONING MARINA L. H. , HIJMERING MICHEL L. , BALLARD DAVID E. , YANG YONGHONG P. , PADLEY ROBERT J. , MORRISON PAUL J. , RABELINK TON J.
Published: April 2021

Endothelin (ET-1) acts as a potent vasoconstrictor in the human kidney, and this vasoconstriction could contribute to the ischemia seen in acute renal failure. In animal studies, the vasoactive properties of ET-1 are known to be ETA receptor-and/or ETB receptor-mediated; however, the receptor subtype involved in the human kidney remains to be defined. In a phase I, single-center, double-blind, randomized, three-period, crossover design, the effects of orally administered ABT-627, a selective ETA receptor antagonist, on renal hemodynamics during ET-1 infusion were evaluated. Two doses of ABT-627 (5 and 20 mg) were compared with placebo and nifedipine. For each dose level of ABT-627, a cohort of nine subjects was studied. A para-aminohippuric acid/inulin clearance test was performed once at the end of each 7-d treatment period. Infusion of ET-1 significantly decreased effective renal plasma flow, GFR, sodium excretion, and urine flow. Pretreatment with 20 mg of ABT-627 significantly decreased mean arterial pressure. In constrast, 7 d of treatment with both doses of ABT-627 did not affect baseline renal parameters. However, because mean arterial pressure decreased, a tendency toward a reduction of renal vascular resistance could indeed be demonstrated. Compared with placebo, both doses of ABT-627 were equally effective in blocking all renal effects caused by ET-1 infusion. In the model of exogenous ET-1 infusion, ABT-627 had a tendency to prevent ET-1-induced renal changes more effectively compared with nifedipine. The contribution of endogenous ET-1 and the ETA receptor in maintaining basal renal vascular tone in the human kidney is small. In addition, compared with placebo, selective ETA receptor antagonism with both doses of ABT-627 completely prevented all renal changes caused by ET-1 infusion.
An Altered Repolarizing Potassium Current in Rat Cardiac Myocytes after Subtotal Nephrectomy
Authors: DONOHOE PAUL , HENDRY BRUCE M. , WALGAMA OMAL V. , BERTASO FEDERICA , HOPSTER DEBORAH J. , SHATTOCK MICHAEL J. , JAMES ANDREW F.
Published: April 2021

Renal failure in humans is associated with electrocardiographic changes including altered QT interval dispersion, which suggests that cardiac myocyte repolarization is abnormal and which appears to correlate with cardiac prognosis. In this study, cardiac myocyte repolarizing currents have been studied in isolated cells from rats 8 wk after subtotal nephrectomy (SNx), using sham-operated animals as controls. In addition, monophasic cardiac action potentials were recorded from the epicardial surface of the left ventricle (LV) apex, LV base, and the right ventricle of isolated perfused hearts paced at 320/min. SNx was associated with cardiac hypertrophy and histologic evidence of myocardial fibrosis, but SNx rats were not hypertensive. Repolarizing K+ currents were measured using whole-cell patch-clamp, and 4-aminopyridine (4-AP)-sensitive transient outward (I
to) and 4-AP-insensitive sustained outward (I
so) components were quantified. After SNx, I
to was increased by two to threefold at voltages from -30 to +60 mV and showed increased heterogeneity. For example, at 0 mV voltage clamp pulse, the median I
to was increased from 3.23 pA/pF in control myocytes (interquartile range 3.20 pA/pF, n = 24) to 5.86 pA/pF in SNx myocytes (interquartile range 7.32 pA/pF, n = 21, P < 0.005). The kinetics of inactivation of I
to were altered after SNx with slowing both of the onset and the recovery from inactivation. The mean time constant of inactivation at +30 mV after SNx was 14.2 ± 1.6 ms (n = 20) compared with control values of 9.8 ± 0.6 ms (n = 23, P < 0.05). Neither I
so nor inward rectifier K+ currents were altered after SNx. The action potential duration (APD50) at the left ventricular base was approximately 20% shorter (P < 0.02) in hearts from SNx rats compared with controls. 4-AP (2 mM) prolonged the APD50 in all regions in hearts from both SNx and control rats and abolished the APD50 shortening in SNx. These results indicate that abnormalities of the cardiac transient outward K+ current contribute to alterations in the cardiac action potential in renal failure and warrant further investigation because they may contribute to altered repolarization and arrythmogenesis.
Explained and Unexplained Ischemic Heart Disease Risk after Renal Transplantation
Authors: KASISKE BERTRAM L. , CHAKKERA HARINI A. , ROEL JOSEPH
Published: April 2021

Whether the high incidence of ischemic heart disease (IHD) among renal transplant patients can be attributed to the same risk factors that have been identified in the general population is unclear. The risk for major IHD events occurring >1 yr after transplantation among 1124 transplant recipients was estimated by using the risk calculated from the Framingham Heart Study (FHS). The FHS risk predicted IHD (relative risk, 1.28; 95% confidence interval, 1.20 to 1.40; P < 0.001); however, the FHS risk tended to underestimate the risk of IHD for renal transplant recipients. This was largely attributable to increased risks associated with diabetes mellitus and, to a lesser extent, age and cigarette smoking for renal transplant recipients. For men, the relative risks for diabetes mellitus were 2.78 (1.73 to 4.49) and 1.53 for the transplant recipient and FHS populations, respectively; the relative risks for age (in years) were 1.06 (1.04 to 1.08) and 1.05, respectively, and those for smoking were 1.95 (1.20 to 3.19) and 1.69, respectively. For women, the relative risks for diabetes mellitus were 5.40 (2.73 to 10.66) and 1.82, respectively. There was a tendency for the risk associated with cholesterol levels to be higher for transplant recipients, compared with the FHS population, but the risks associated with high-density lipoprotein cholesterol levels and BP appeared to be comparable. Independent of these and other risk factors, the adjusted risk of IHD for the transplant recipient population has decreased. Compared with the era before 1986, transplantation between 1986 and 1992 was associated with a lower relative risk of 0.60 (0.39 to 0.92); transplantation after 1992 was associated with an even lower relative risk of 0.27 (0.11 to 0.63) for IHD. Of concern was the fact that dihydropyridine calcium channel antagonists were associated with an increased risk for IHD (relative risk, 2.26; 95% confidence interval, 1.24 to 4.12; P = 0.008), and this association was independent of other antihypertensive agents and risk factors. Therefore, although the FHS risk predicts IHD after renal transplantation, it tends to underestimate the risks, especially the risk associated with diabetes mellitus. The unexpected finding that dihydropyridine calcium channel antagonists were associated with an increased IHD risk merits further evaluation.
Interleukin-12 from Intrinsic Cells Is an Effector of Renal Injury in Crescentic Glomerulonephritis
Authors: TIMOSHANKO JENNIFER R. , KITCHING A. RICHARD , HOLDSWORTH STEPHEN R. , TIPPING PETER G.
Published: April 2021

Interleukin-12 (IL-12) directs the cognate nephritogenic T helper type 1 responses that initiate renal injury in murine crescentic glomerulonephritis (GN). The recent demonstration of IL-12 production by intrinsic renal cells, including mesangial and proximal tubular cells, raises the possibility that IL-12 from nonimmune cells may contribute to inflammatory renal injury. To address this possibility, the development of sheep anti-mouse glomerular basement membrane globulin—induced crescentic GN was studied in C57BL/6 wild-type (WT), IL-12—deficient (IL-12 -/-), and IL-12 “chimeric” mice. IL-12 chimeric mice were produced by transplantation of WT bone marrow into IL-12 -/- mice to restore IL-12 production by immune cells, while leaving them deficient in renal IL-12 production. WT and “sham” chimeric mice (normal bone marrow transplanted into WT mice) developed crescentic GN with glomerular T-cell and macrophage recruitment and impaired renal function (elevated proteinuria and serum creatinine) 10 d after initiation of GN. IL-12 -/- mice showed significant protection from GN. Chimeric IL-12 mice showed significant attenuation of crescent formation, glomerular T-cell and macrophage accumulation, and renal impairment, compared with WT and sham chimeric mice, but were not protected to the same extent as IL-12 -/- mice. IL-12 chimeric mice showed no attenuation of their systemic cognate immune response to the nephritogenic antigen (sheep globulin), indicated by antigen-specific circulating antibody and cutaneous delayed-type hypersensitivity. These studies indicate that IL-12 produced by non—bone marrow derived intrinsic renal cells contributes to immune renal injury. They provide the first in vivo demonstration of a proinflammatory role for an intrinsic renal cell—derived cytokine in renal inflammation.
A Randomized Trial of High-Dose Compared with Low-Dose Omega-3 Fatty Acids in Severe IgA Nephropathy
Authors: DONADIO JAMES V. , LARSON TIMOTHY S. , BERGSTRALH ERIK J. , GRANDE JOSEPH P.
Published: April 2021

Tested was the hypothesis that high-dose omega (ω)-3 fatty acids will be more effective than low-dose ω-3 fatty acids in preserving renal function in patients with severe IgA nephropathy in a randomized, open-label, parallel-group clinical trial. Patients were assigned to receive either high-dose fatty acids (EPA 3.76 g and DHA 2.94 g) or low-dose fatty acids (EPA 1.88 g and DHA 1.47 g), both given daily in a highly purified ethyl ester concentrate (Omacor). Patients were treated for a minimum of 2 yr in the absence of a treatment failure or until study closure (January 2000). Seventy-three patients were enrolled in the trial with two ranges of elevated serum creatinine (SC): 63 patients (86%) with a range of 1.5 to 2.9 mg/dl and 10 patients (14%) with a range of 3.0 to 4.9 mg/dl. The primary end point, within-patient rates of change in SC (2-yr minimum), showed an annualized median increase in SC of 0.08 mg/dl per yr in the low-dose group and 0.10 mg/dl per yr in the high-dose group (P = 0.51). Patients in the lower entry SC range had lower SC slopes (P = 0.02) and less end-stage renal disease (ESRD) (P < 0.001) compared with those in the higher entry SC range. No patient died, and 18 patients developed ESRD: 10 in the low-dose group and 8 in the high-dose group (P = 0.56). SC slopes were significantly lower, and survival free of ESRD was significantly higher (both, P = 0.04) in the 63 Omacor-treated patients compared with the 22 placebo-treated patients from our previously reported clinical trial in which both groups had a similar level of renal impairment. Patient compliance was excellent, and no serious adverse events were noted. Low-dose and high-dose ω-3 fatty acids were similar in slowing the rate of renal function loss in high-risk patients with IgA nephropathy, particularly those with moderately advanced disease.
Cardiac Natriuretic Peptides Are Related to Left Ventricular Mass and Function and Predict Mortality in Dialysis Patients
Authors: ZOCCALI CARMINE , MALLAMACI FRANCESCA , BENEDETTO FRANCESCO ANTONIO , TRIPEPI GIOVANNI , PARLONGO SAVERIO , CATALIOTTI ALESSANDRO , CUTRUPI SEBASTIANO , GIACONE GIUSEPPE , BELLANUOVA IGNAZIO , COTTINI EMILIO , MALATINO LORENZO SALVATORE
Published: April 2021

This study was designed to investigate the relationship among brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and left ventricular mass (LVM), ejection fraction, and LV geometry in a large cohort of dialysis patients without heart failure (n = 246) and to test the prediction power of these peptides for total and cardiovascular mortality. In separate multivariate models of LVM, BNP and ANP were the strongest independent correlates of the LVM index. In these models, the predictive power of BNP was slightly stronger than that of ANP. Both natriuretic peptides also were the strongest independent predictors of ejection fraction, and again BNP was a slightly better predictor of ejection fraction than ANP. In separate multivariate Cox models, the relative risk of death was significantly higher in patients of the third tertile of the distribution of BNP and ANP than in those of the first tertile (BNP, 7.14 [95% confidence interval (CI), 2.83 to 18.01, P = 0.00001]; ANP, 4.22 [95% CI, 1.79 to 9.92, P = 0.001]), and a similar difference was found for cardiovascular death (BNP, 6.72 [95% CI, 2.44 to 18.54, P = 0.0002]; ANP, 3.80 [95% CI, 1.44 to 10.03, P = 0.007]). BNP but not ANP remained as an independent predictor of death in a Cox's model including LVM and ejection fraction. Cardiac natriuretic peptides are linked independently to LVM and function in dialysis patients and predict overall and cardiovascular mortality. The measurement of the plasma concentration of BNP and ANP may be useful for risk stratification in these patients.
Öğrencilerin Yazma Özerkliği Becerileri ve Yazma Kaygılarının Nitel ve Nicel Yöntemlerle İncelenmesi
Authors: SÜĞÜMLÜ Üzeyir , ALVER Mehmet
Published: April 2021

Araştırmanın amacı; öğrencilerin yazma özerkliği becerileri ve yazma kaygılarını nitel ve nicel yöntemlerle incelemektir. Araştırma süreci iki aşamadan oluşmaktadır. Araştırmanın birinci aşaması nitel yöntemle, ikinci aşaması ise nicel yöntemle yürütülmüştür. Araştırmanın çalışma gruplarını, 2019-2020 eğitim-öğretim yılı güz yarıyılında bir ilin ortaokullarında görev yapan 26 Türkçe öğretmeni ve aynı ilin ortaokullarında öğrenim gören 280 sekizinci sınıf öğrencisi oluşturmaktadır. Araştırmanın verileri; yarı yapılandırılmış görüşme formu, Yazma Özerkliği Ölçeği ve Yazma Kaygısı Ölçeği ile toplanmıştır. Araştırmanın nitel verilerinin analizi, MAXQDA 20 nitel veri analizi programıyla yapılmış ve veriler, içerik analizi tekniği ile çözümlenmiştir. Araştırmanın nicel verilerinin analizi, SPSS 25.0 paket programıyla yapılmış ve veriler, çeşitli istatistik teknikleri kullanılarak çözümlenmiştir. Araştırma ile öğrencilerin yazma özerkliği durumlarının yeterli görülmediği, yazma çalışmalarında yazma kaygıları yaşadıkları, yazma özerkliği ile yazma kaygısı düzeyleri arasında negatif yönlü anlamlı bir ilişkinin olduğu ve yazma kaygısının yazma özerkliğinin anlamlı bir yordayıcısı olduğu sonuçlarına ulaşılmıştır.
Ortaokul Öğrencilerinin Eleştirel Düşünme Becerilerinin İncelenmesi
Authors: METE Gülşah
Published: April 2021

Bu araştırma ile sekizinci sınıf öğrencilerinin eleştirel düşünme düzeylerinin belirlenmesi amaçlanmaktadır. Araştırmanın bir başka amacı ise, öğrencilerin; cinsiyet, aile yapısı, kardeş sayısı, anne ve baba eğitim düzeyi, okuma alışkanlığı, spor / sanat eğitimi alma (veya bu tür etkinliklere katılma), Türkçe dersi başarıları gibi özellikleri ile eleştirel düşünme düzeyleri arasında bir ilişki olup olmadığını ortaya çıkarmaktır. Nicel araştırma yaklaşımlarından biri olan betimleyici ilişkisel tarama modelinin kullanıldığı çalışma, 2020-2021 eğitim öğretim yılı ilk yarı yılında Muğla’da öğrenim gören 237 sekizinci sınıf öğrencisi ile gerçekleştirilmiştir. Araştırmanın verileri, Görücü (2014) tarafından geliştirilen Eleştirel Düşünme Ölçeği ile toplanmıştır. Elde edilen veriler SPSS programı ile analiz edilmiştir. Araştırmada ulaşılan bulgular; sekizinci sınıf öğrencilerinin eleştirel düşünmelerinin orta düzeyde olduğu, öğrencilerin eleştirel düşünme düzeylerinin anne eğitim düzeyi, okuma alışkanlığı, spor / sanat eğitimi alma (veya bu tür etkinliklere katılma) ve Türkçe dersi başarılarına göre anlamlı bir ilişki olduğunu ortaya koymaktadır.
A method for the temperature-controlled extraction of DNA from ancient bones v1
Authors: Essel Elena , Meyer Matthias , Korlevic Petra
Published: April 2021

We here provide a protocol for the decontamination of ancient bones and teeth that is based on a temperature-controlled, sequential release of DNA. DNA can be extracted from all fractions generated with this method and the fraction with the highest proportion of endogenous DNA identified for further analysis. The protocol proceeds through repeated incubation of the sample powder in phosphate buffer at 37, 60 and 90 °C, followed by the complete lysis of the residual sample powder. As DNA is denatured at high temperature, subsequent DNA extraction and library preparation has to be performed using methods optimized for single-stranded DNA.
Preparing Data for vContact from Proteins (Cyverse) v5
Authors: Bolduc Benjamin
Published: April 2021

Preparing data for use in vContact by usingVirSorted Ocean Sampling Day (2014) contigs, using tools available inCyverse. This protocol creates a BLAST DB, BLASTs sequences, and creates a gene-to-contig mapping file. Results from this protocol are suitable for vContact-PCs.
KAMU HİZMETİ MOTİVASYONUNA ÖRGÜTSEL BAĞLILIĞIN ETKİSİ: NEVŞEHİR İLİ LİSE ÖĞRETMENLERİ UYGULAMASI
Authors: Alkaya Aylin , Taştekin İlknur
Published: April 2021

Kamu hizmeti motivasyonu kamu yönetimi bilimi içinde kamu çalışanlarının başkalarına ve topluma yarar sağlamak amacıyla işini yerine getirmeye çalışma yönelimi olarak tanımlanabilmektedir. Örgütsel bağlılık çalışanların örgütsel değerlere bağlı olması ve kendilerini kurumun bir parçası olarak görmesidir. Çalışmanın amacı, kamu kurumu liselerde çalışan öğretmenlerin kamu hizmeti motivasyonlarında örgütsel bağlılıklarının etkisini araştırmaktır. Araştırmanın örneklemini Nevşehir şehir merkezinde kamu kurumu liselerinde görevli öğretmenler oluşturmaktadır. Veri toplama yöntemi olarak internet anketi uygulanmıştır. Kamu hizmeti motivasyonu üzerinde örgütsel bağlılığın etkisini belirlemek amacıyla çok değişkenli regresyon analizi uygulanmıştır. Araştırma bulgularından kamu hizmeti motivasyonu üzerinde örgütsel bağlılığın anlamlı etkisinin olduğu belirlenmiştir.
SAĞLIK ALANINDA ÖĞRENİM GÖREN YÜKSEKÖĞRENİM ÖĞRENCİLERİNİN İNTERNETE YÖNELİK TUTUMLARININ E-SAĞLIK OKURYAZARLIK DÜZEYLERİNE ETKİSİ
Authors: Yıldız Ahmet
Published: April 2021

Bu araştırmanın amacı sağlık öğrencilerinin internete yönelik tutumlarının e-sağlık okuryazarlık düzeylerine etkisini araştırmaktır. Araştırmada veri toplama aracı olarak İnternete Yönelik Tutum Ölçeği ve E-Sağlık Okuryazarlığı Ölçeği kullanılmıştır. Araştırma, İlk ve Acil Yardım, Fizyoterapi, Sağlık Kurumları İşletmeciliği ve Yaşlı Bakımı programlarında okuyan 519 öğrenci üzerinde yapılmıştır. Araştırmada internete yönelik tutum ölçeği alt boyutları olan internet kullanımı, internetin yararlı olduğuna inanma ve internetten hoşlanma boyutları bağımsız değişkenler, e-sağlık okuryazarlığı ise bağımlı değişken olarak ele alınmıştır. Bağımsız değişkenler ile bağımlı değişken arasındaki ilişki pearson korelasyon analizi ile, bağımsız değişkenlerin bağımlı değişken üzerindeki etkisi ise regresyon analizi ile test edilmiştir. Araştırma sonucunda e-sağlık okuryazarlığı ile internet kullanımı, internetin yararlı olduğuna inanma ve internetten hoşlanma boyutları arasında orta düzeyde ve istatistiksel olarak anlamlı ilişki bulunmuştur (p
Bazı Yerel Üzüm Çeşitlerinde (Vitis vinifera L.) Stoma Özellikleri ile Fiziksel ve Kimyasal Özellikler Arasındaki İlişkiler
Authors: ARSLAN Tuncer , DOĞAN Adnan , UYAK Cuneyt , GÜZEL Deniz Uğur
Published: April 2021

Bu çalışmanın amacı, Yüksekova (Hakkari) yöresinde yetiştirilen 12 yerel üzüm çeşidinin stoma yoğunluklarını ve boyutlarını belirlemektir. Ayrıca, stoma özellikleri ile fiziksel ve kimyasal özellikler arasındaki ilişkileri saptamaktır. Stoma özelliklerini belirlemek amacıyla her çeşidin yaz sürgünlerinin 4-5. Boğumlarından yaprak örnekleri alınmış ve yaprak yüzeyinin farklı yerlerinden (dip, orta, uç) kalıp alma yöntemi ile stoma yoğunlukları ve boyutları belirlenmiştir. Stoma yoğunluklarının 166.13-247.12 adet mm², stoma boylarının 22.63-27.88 µm, stoma enlerinin ise 14.59-19.00 µm değerleri arasında değiştiği tespit edilmiştir. Yapraklardaki stoma yoğunluğu ile yaprak büyüklüğü ve salkım ağırlığı arasında pozitif yönlü, stoma yoğunluğu ile üzüm şırasında SÇKM arasında negatif yönlü anlamlı bir korelasyon bulunmuştur.
The Influence of Age and Exposure Time on the Susceptibility of Carpophilus hemipterus Pupa to High Carbon Dioxide with Low Oxygen Treatment
Authors: TÜTÜNCÜ Şule
Published: April 2021

Modified/controlled atmosphere applications, as an alternative to the chemical treatments, are an effective technique in controlling pest of stored products, especially dried fruits. In gas tight units, it is applied with the principle of preventing the insect respiration by changing the oxygen (O2), carbon dioxide (CO2) and nitrogen (N2) gas levels of the atmosphere. In the study, 1-, 2- and 3- d-old pupae of dried fruit beetle, Carpophilus hemipterus (L.), which is an important dried fruit pest, were exposed to the modified / controlled atmosphere. The modified/controlled atmosphere consisting of 2.1% O2 + 90% CO2 + 7.9% N2 gas mixture was applied for 48, 72, 96 and 120 h at 20°C and 75 ± 5% relative humidity. One, two and three d old pupae responded similarly to modified/controlled atmosphere application. Mortality rates remained close in each exposure time and no significant difference was found between age groups. Unlike the age factor, the exposure time was found to be statistically significant and the mortality rates increased as the exposure time increased in each age group. The highest mortality rates were found as 38, 60 and 47% in 1-, 2- and 3-d old pupae after 120 h of application, respectively.
Internet of Things (IoT) in Agriculture: The Idea of Making the Fields Talk
Authors: Vadlamudi Siddhartha
Published: April 2021

The demand for agricultural crops is moving at a slower pace compared to the human population. There must be increased agricultural productivity. Ongoing innovative advances have added to the ascent of exactness agribusiness, empowering farmers to settle on better choices with more data about their soil, water, yield, and local environment, yet has been generally restricted to popularized and production of cash crops. The objective of smart agribusiness research is to ground a dynamic emotionally supportive network for the management of farms. IoT is being used in agriculture to get to know the crop field by utilizing sensors for monitoring, controlling in the field. It is used to get to know the crop field by utilizing sensors for monitoring, controlling in the field, etc. Recent developments in IoT, comparison between traditional and smart agriculture, and the roles of IoT in agriculture were analyzed in this study. The articles were purposively inspected while the qualitative data gathered was dissected utilizing content analysis. Summarily, the rise of smart agriculture has lowered the practice of traditional farming, as it has enhanced it in no small way. The research likewise showed that the lacuna in agriculture can be filled with IoT. Scalability in technology should be encouraged without affecting the functionalities of the existing infrastructures.
The Internet of Things (IoT) and Social Interaction: Influence of Source Attribution and Human Specialization
Authors: Vadlamudi Siddhartha
Published: April 2021

The evolvement of IT has open new doors in connecting many devices to the worldwide web that successively produce data around the physical setting using the IoT. However, the system of message turns out to be slightly intricate in human specialization-internet of things communication for the reason that the IoT is a system including diverse objects transferring data This study examines the hypothetical pathway by which the changes in source attribution that is multiple against single and specialization that is multi-functionality against single functionality of IoT devices affect the quality of human- internet of things interaction. The result from the study obtained from 80 participants that took part in the experiment shows that multiple source attribution improves the condition of information basically for the low-involvement people supports further probes the multiple source effects. However, this study recommends improvement of attribution source and human specialization-IoT.
AVRUPA BİRLİĞİ ÜLKELERİNDE SOSYAL SERMAYE VE KONJONKTÜREL DALGALANMALAR İLİŞKİSİNİN ANALİZİ
Authors: ÇETİN Semih
Published: April 2021

Son yıllarda, büyümenin dinamikleri arasında tartışılmaya başlanan ve kalkınma literatüründe kendisine yer edinen sosyal sermaye konusuna yönelik ilgi artmaktadır. Diğer taraftan konjonktürel dalgalanmaların refah ve büyüme üzerine olan olumsuz etkileri sebebiyle, bu dalgalanmaların tüm olası sebeplerini araştırmak önemli görülmektedir. Bu açıdan bakıldığında, sosyal sermayenin ekonomik performans üzerinde nasıl bir etki yarattığı önemli bir araştırma konusu olarak karşımıza çıkmaktadır. Bu çalışmada 1995-2017 yılları arasında 15 AB üyesi ülkeden oluşan bir örneklem için, sosyal sermaye ve konjonktürel dalgalanmalar arasındaki ilişki tam değiştirilmiş en küçük kareler (FMOLS) yöntemiyle araştırılmıştır. Çalışmada, sosyal sermaye ile konjonktürel dalgalanmalar arasında negatif ve istatistiki olarak anlamlı bir ilişki olduğuna dair kanıt bulunmuştur.
A case–control study to predict the risk of gestational diabetes mellitus by initial fasting blood sugar or past gestational history
Authors: Ezazi Bojnordi Tahmineh , Hantoushzadeh Sedigheh , Sabzevary Masomeh , Heidari Zahra
Published: April 2021

Background: Gestational diabetes mellitus (GDM) deserves proper prevention, diagnosis, and management due to healthcare implications from both maternal and fetal concerns.
Objective: To evaluate the rate and investigate the risk factors for developing GDM.
Materials and Methods: In this case-control, universal screening for GDM between 24 and 28 wk of gestation was performed in 613 pregnant women attending a prenatal clinic in Tehran who were followed-up until delivery between March 2017 to March 2018. Of the 613 women, 143 had GDM and 470 had normal glucose tolerance test as the primary diagnosis. Some GDM risk factors were compared in two groups.
Results: Impaired glucose tolerance test was detected in 143 (23.3%) patients. Prevalence of GDM was higher in the first-trimester fasting blood sugar (FBS) > 90 qmg/dl group (p < 0.001). Comparison of the GDM and the normal glucose tolerance test groups demonstrated significant differences in maternal age, first-trimester FBS, third-trimester vitamin D level, maternal platelet count, maternal body mass index (BMI) (before 12 wk of gestation), weight gain during pregnancy, and the history of gestational complications in previous pregnancy (p < 0.01). In logistic regression, GDM was independently associated with older maternal age, higher first-trimester FBS, the history of gestational complications in previous pregnancy, lower third-trimester vitamin D level, and higher maternal platelet count (p < 0.01).
Conclusion: Both patients with higher initial FBS and the history of gestational complications in previous pregnancy should be considered high risk for GDM and screened earlier.
Key words: Diabetes Mellitus, Gestational, Blood glucose, Risk factor.