bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Intraindividual Variability of Cyclosporin A Exposure Reduces Chronic Rejection Incidence and Health Care Costs
Authors: KAHAN BARRY D. , WELSH MARIA , URBAUER DIANA L. , MOSHEIM MELINDA B. , BEUSTERIEN KATHLEEN M. , WOOD MARTHA R. , SCHOENBERG LINDA P. , DICESARE JOSEPH , KATZ STEPHEN M. , VAN BUREN CHARLES T. 
Published: April 2021

Abstract.
The present study applied a receiver operating characteristic (ROC) analysis to assess the role of intraindividual variability of cyclosporin A (CsA) drug exposure in predisposing renal transplant recipients to the occurrence of chronic rejection, as well as to increased health care costs using a resource-based economic analysis. Two hundred and four adult renal transplant recipients were treated with tapering doses of prednisone (Pred) and with a concentration-controlled strategy that selected doses of the olive oil-based formulations of CsA (Sandimmune®) that achieved target concentrations based on serial pharmacokinetic profiles. The ROC analysis revealed an inflection point of plots of the coefficient of variation (%CV) of CsA exposure versus the risk of chronic rejection at ≥28.4% for the average concentration (C
av), i.e., the dosing interval-corrected area under the concentration-time curves, and ≥36% for the trough concentration (C
0). The incidence of chronic rejection over a period of 5 yr was 24% among the less variable (LV) versus 40% among the variable (V) cohort. The economic analysis revealed that the total mean facility and physician costs per patient were $48,789 versus $60,998, respectively (P < 0.01). The degree of variability displayed by any individual could only be predicted by serial measurements of CsA concentrations, and not by demographic features, laboratory determinations, clinical characteristics, individual or mean values of any observed CsA concentration, or other pharmacokinetic parameters calculated following a single drug exposure. Thus, strategies that reduce intrapatient variability of CsA exposure over time may lead to reductions in chronic allograft loss and in treatment costs.
Differential Effects of Sera from Normotensive and Hypertensive Pregnant Women on Ca2+ Metabolism in Normal Vasular Smooth Muscle Cells
Authors: GREEN JACOB , ASSADY SUHEIR , NAKHOUL FARID , BICK TOVA , JAKOBI PETER , ABASSI ZAID 
Published: April 2021

Abstract.
The clinical features of preeclampsia have been traditionally ascribed to a generalized vascular endothelial cell dysfunction. The present study investigates the effect of sera from preeclamptic women and normal pregnancy on the metabolism of intracellular Ca2+ concentration ([Ca2+]i) in normal cultured vascular smooth muscle cells (VSMC). Sera were obtained from normotensive pregnant women (NTP) (n = 17), preeclamptic women (PE) (n = 15), pregnant women with chronic (essential) hypertension (pregnant EHT) (n = 8), non-pregnant women with essential hypertension (non-pregnant EHT) (n = 12), and age-matched non-pregnant normotensive women (NNP) (n = 18). Serum (10%) was applied to both primary cultures of rat aortic smooth muscle cells and to the A-10 vascular muscle cell line. Levels of [Ca2+]i were determined fluorometrically. After a 4-h incubation with serum, basal [Ca2+]i was not significantly altered. However, compared with normal pregnant sera, PE sera markedly reduced hormonally induced Ca2+ transients. Thus, following acute stimulation of rat VSMC (primary cultures) with 10-8M angiotensin II, peak [Ca2+]i responses (% increment over baseline) were 443 ± 22, 184 ± 18, 259 ± 12, 274 ± 23, and 255 ± 15% in NTP, PE, pregnant EHT, non-pregnant EHT, and NNP, respectively (P <0.01 PE versus NTP, P <0.05 PE versus NNP and pregnant and non-pregnant EHT). These effects of sera on [Ca2+]i were qualitatively reproduced in platelets obtained from healthy volunteers. Also, depolarization-activated Ca2+ influx in VSMC was affected by the different sera groups in a manner similar to that seen with hormonally induced [Ca2+]i responses. The altered [Ca2+]i changes by PE sera disappeared 5 wk after delivery. The effect of the different sera groups on hormonally triggered Ca2+ transients in normal VSMC, as well as the normalization of [Ca2+]i responses after delivery, suggest the presence of a circulating serum factor in PE. Inasmuch as [Ca2+]i is the major determinant of VSMC tone, it is possible that consequent to the attenuation of [Ca2+]i responses, this putative circulating factor counterbalances the intense vasoconstriction in PE.
Vascular Endothelial Growth Factor Receptors in Human Mesangium in Vitro and in Glomerular Disease
Authors: THOMAS STEPHEN , VANUYSTEL JOHANN , GRUDEN GABRIELLA , RODRÍGUEZ VERÓNICA , BURT DAVINA , GNUDI LUIGI , HARTLEY BARRY , VIBERTI GIANCARLO 
Published: April 2021

Abstract.
Mesangial cell proliferation and growth factor over-expression are characteristic features of several glomerular diseases. Vascular endothelial growth factor (VEGF), a potent mitogen, is expressed in podocytes in the glomerulus, and VEGF receptors (flt-1, KDR, and neuropilin-1) are present on endothelial cells and other cell types. This study examined whether human mesangial cells (HMC) express VEGF receptors in vitro and ex vivo and evaluated the effect of VEGF on HMC proliferation. All receptor types were detected in HMC in vitro by immunofluorescence and Western blotting. VEGF165 induced a dose-responsive increase in 3H-thymidine incorporation (25 ng/ml VEGF165: 2.3-fold increase; 50 ng/ml: 3.8-fold; 100 ng/ml: 4.8-fold; 200 ng/ml: 3.4-fold; P = 0.016) and in cell number (50 ng/ml VEGF165: 1.2-fold increase; 100 ng/ml: 1.6-fold; 200 ng/ml: 1.4-fold; P = 0.005), effects prevented by an anti-VEGF165 polyclonal neutralizing antibody (100 μg/ml). The proliferative effect was confirmed by a tetrazolium dye-based assay (100 ng/ml VEGF165: 1.4-fold increase). In ex vivo experiments, VEGF receptors in biopsy material from normal and diseased kidneys were detected by immunohistochemistry. No mesangial flt-1 receptor staining was seen in normal renal cortical tissue samples, and only weak mesangial KDR staining was detected. In contrast, mesangial flt-1 and KDR receptor staining were both clearly seen in biopsy samples from proliferative renal diseases. In conclusion, flt-1, KDR, and neuropilin-1 are present on cultured HMC, and VEGF165 induces HMC proliferation. In addition, the flt-1 and KDR receptors are expressed in the mesangium in mesangioproliferative disease.
Chromosomal Mapping of a Major Quantitative Trait Locus Regulating Compensatory Renal Growth in the Rat
Authors: PRAVENEC MICHAL , ZIDEK VACLAV , MUSILOVA ALENA , KR[Combining Caron]EN VLADIMIR , BILA VLASTA , NICOLANTONIO ROBERT DI 
Published: April 2021

Abstract.
Despite extensive research conducted over the past century, the mechanisms of compensatory renal growth (CRG) remain a mystery. Insight into the mechanisms that regulate CRG might be gained by identifying genetic factors that influence this complex phenotype. In a large set of recombinant inbred strains derived from the spontaneously hypertensive rat and the Brown Norway rat, a genome scan for quantitative trait loci (QTL) that regulate CRG was performed. The CRG score was expressed as a ratio of the weight of the remnant right kidney at 8 wk of age to the weight of the left kidney at 5 wk of age, both adjusted for body weight. QTL mapping was performed using Map Manager QT and the strain distribution patterns of more than 600 genetic markers. It was found that CRG after unilateral nephrectomy is a multifactorially determined trait with a substantial genetic component. The heritability of CRG approached 40%. Genome wide scan analysis revealed significant evidence of linkage to a region of rat chromosome 4 designated Crg 1 that accounted for more than 50% of the additive genetic variance of CRG in the recombinant inbred strains. The detection of a major QTL influencing CRG in the rat should provide new opportunities for identifying mechanisms that regulate this historically enigmatic phenomenon and may also have implications for research on the pathogenesis of end-stage kidney disease.
Pharmacokinetics of Intermittent Intravenous Cefazolin and Tobramycin in Patients Treated with Automated Peritoneal Dialysis
Authors: MANLEY HAROLD J. , BAILIE GEORGE R. , FRYE REGINALD , HESS LORRAINE D. , MCGOLDRICK M. DONALD 
Published: April 2021

Abstract.
There is increasing use of intermittent dosing of antibiotics to treat peritoneal dialysis (PD)-related peritonitis. The disposition of intravenous cefazolin and tobramycin was studied in automated PD (APD) patients. Ten patients were recruited and received a single intravenous dose of cefazolin (15 mg/kg) and tobramycin (0.6 mg/kg). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1 to 3 (on cycler), and at the end of dwells 4 to 5 (off cycler) for a 24-h period. Baseline and 24-h urine samples were collected. Pharmacokinetic parameters were calculated using a monoexponential model. Cefazolin and tobramycin half-lives were markedly different on cycler than off cycler (cefazolin on cycler: 10.67 ± 4.66 h; cefazolin off cycler: 23.09 ± 5.6 h; P = 0.001; tobramycin on cycler: 14.27 ± 4.53 h; tobramycin off cycler: 68.5 ± 26.47 h; P < 0.001). Mean serum and dialysate concentrations were above minimum inhibitory concentrations of susceptible organisms throughout the 24-h period for both drugs with intravenous administration. A model was developed to examine serum and dialysate concentrations after intermittent intraperitoneal administration of 15 mg/kg cefazolin and 0.6 mg/kg tobramycin. Model-predicted intraperitoneal cefazolin provides adequate serum and dialysate concentrations for 24 h. Intermittent intraperitoneal tobramycin doses must be 1.5 mg/kg for one exchange during the first day and then given as 0.5 mg/kg thereafter. It is concluded that the current empiric dosing recommendations for PD-related peritonitis may be adequate for cefazolin (15 to 20 mg/kg); however, tobramycin doses must be changed to 1.5 mg/kg intraperitoneally on day 1, then to 0.5 mg/kg intraperitoneally thereafter in APD patients.
Contribution of Prolonged Ischemia and Donor Age to Chronic Renal Allograft Dysfunction
Authors: TULLIUS STEFAN GU[Combining Diaeresis]NTHER , REUTZEL-SELKE ANJA , EGERMANN FRANK , NIEMINEN-KELHA[Combining Diaeresis] MELINA , JONAS SVEN , BECHSTEIN WOLF OTTO , VOLK HANS-DIETER , NEUHAUS PETER 
Published: April 2021

Abstract.
As a consequence of an advancing discrepancy between supply of suitable grafts and demand from potential recipients, less than optimal organs are increasingly being used. Although clinical studies demonstrate the involvement of various risk factors, including donor age and duration of ischemia on long-term graft outcome, their individual contribution and correlation has not been followed experimentally. After cold ischemic times of 5, 60, and 120 min, kidney allografts of 3-, 12-, and 18-mo-old Fischer 344 donors were transplanted into 3-mo-old Lewis rats. Age-related changes were examined in matched native uninephrectomized controls. Proteinuria and creatinine clearance were determined, and histologic and immunohistologic studies were assessed and quantified at the end of the observation period (20 wk). All grafts functioned satisfactorily with the exception of one graft each from 12- and 18-mo-old donors with prolonged ischemia (120 min). Functional deterioration and structural changes progressed in parallel to increasing donor age and prolonged ischemia. The impact of expanded ischemia was particularly detrimental in grafts from older donor animals. Donor age and duration of ischemia act in a synergistic manner in our model. Brief ischemic times seem of particular relevance when grafts from older donors are being used.
Reactive Oxygen Species Stimulate p44/42 Mitogen-Activated Protein Kinase and Induce p27Kip1
Authors: HANNKEN TETE , SCHROEDER REGINE , ZAHNER GUNTHER , STAHL ROLF A. K. , WOLF GUNTER 
Published: April 2021

Abstract.
Angiotensin II (AngII) induces G1 phase arrest and hypertrophy of cultured renal proximal tubular cells. In previous studies, it was shown that these effects depend on oxygen radical-mediated induction of p27Kip1, an inhibitor of cyclin-dependent kinases. The present study was undertaken to investigate whether mitogen-activated protein (MAP) kinases serve as signaling intermediates between AngII-induced oxidative stress and induction of p27Kip1. AngII (10-7 M) induces a biphasic phosphorylation pattern of p44/42 MAP kinase with an early phosphorylation after 2 min and a later, second phosphorylation peak after prolong incubation (12 h) in cultured proximal tubular cells from two different species (MCT and LLC-PK1 cells). Total protein expression of MAP kinase was not changed by AngII. These phosphorylation patterns of p44/42 MAP kinase caused activation of the enzyme, as detected by phosphorylated MAP substrate Elk-1 after immuno-precipitation of MAP kinase. Exogenous H2O2 also stimulates a biphasic phosphorylation of p44/42 MAP kinase. The flavoprotein inhibitor diphenylene iodinium, as well as the antioxidant N-acetylcysteine, prevented AngII-induced p44/42 MAP kinase phosphorylation, indicating involvement of reactive oxygen species generated by membrane-bound NAD(P)H oxidase. The MAP kinase kinase inhibitor PD98059 completely inhibits AngII-induced p27Kip1 expression and 3[H]leucine incorporation into proteins as a previously established marker of cell hypertrophy. PD98059 did not attenuate AngII-stimulated intracellular synthesis of oxygen radicals. Transient transfection with p44/42 MAP kinase antisense, but not sense, phosphorothioate-modified oligonucleotides also prevented AngII-induced MAP kinase phosphorylation, p27Kip1 expression, and cell hypertrophy. Furthermore, induction of p27Kip1 by H2O2 was also abolished in the presence of PD98059. Although AngII induces phosphorylation of the stress-activated p38 MAP kinase, inhibition of this enzyme with SB203580 failed to attenuate induced p27Kip1 expression and hypertrophy. These data provide evidence that AngII- mediated oxygen stress leads to the phosphorylation of p44/42 MAP kinase in proximal tubular cells. Activation of this enzyme is essential for p27Kip1 expression, G1 phase arrest, and hypertrophy of proximal tubular cells. These findings may lead to new concepts concerning interference of the development of proximal tubular hypertrophy, which may eventually turn into a maladaptive process in vivo leading ultimately to tubular atrophy and tubulointerstitial fibrosis.
Growth Hormone Increases Inducible Nitric Oxide Synthase Expression in Mesangial Cells
Authors: DOI SONIA Q. , JACOT TERRY A. , SELLITTI DONALD F. , HIRSZEL PRZEMYSLAW , HIRATA MARIO H. , STRIKER GARY E. , STRIKER LILIANE J. 
Published: April 2021

Abstract.
Mice transgenic for bovine growth hormone (GH) develop progressive glomerulosclerosis. However, the proximal signaling events that lead to increased matrix deposition in this pathologic condition are still unclear. Components of the L-arginine metabolic pathway, especially inducible nitric oxide (NO) synthase (iNOS), ornithine aminotransferase (OAT), and ornithine decarboxylase (ODC), have been associated with glomerular scarring. In this study, mesangial cells were treated with GH, and the expression of iNOS, ODC, and OAT was determined using reverse transcription-PCR. In addition, nitrite accumulation in the conditioned media of mesangial cell cultures was measured in the presence or absence of GH. The findings revealed that GH increased iNOS transcript levels in a dose-dependent manner, with the highest levels being attained at GH concentrations of 20 to 50 ng/ml. The GH-induced increase in iNOS transcript levels was accompanied by a significant increase in nitrite concentrations in conditioned media, which was blocked by the addition of L-N
G-monomethylarginine. The effect of GH (50 ng/ml) in eliciting nitrite production was as potent as that of bacterial lipopolysaccharide (10 μg/ml). The expression of OAT and ODC, in contrast, was not altered at any of the GH concentrations tested. GH receptor mRNA was also expressed by mesangial cells, independently of the GH concentration present in the cell culture medium. These data indicate that GH may interact with its receptor to regulate the L-arginine/NO pathway in mesangial cells, by directly modulating iNOS expression and NO production, without altering the arginase/OAT/ODC pathway.
Food Restriction Prevents Advanced Glycation End Product Accumulation and Retards Kidney Aging in Lean Rats
Authors: TEILLET LAURENT , VERBEKE PHILIPPE , GOURAUD SABINE , BAKALA HILAIRE , BOROT-LALOI CAROLINE , HEUDES DIDIER , BRUNEVAL PATRICK , CORMAN BRUNO 
Published: April 2021

Abstract.
Tissue content of advanced glycation end products (AGE) increases with age and contributes to the changes in structure and function of the renal and cardiovascular systems. The effect of chronic food restriction on this AGE accumulation was investigated in lean WAG/Rij rats. A 30% food restriction performed from 10 to 30 mo in female rats reduced their mean body weight from 240 ± 7 to 160 ± 12 g, but did not modify their survival. AGE collagen content increased from 14.3 ± 5.5 to 104.7 ± 13.0 arbitrary units per microgram (AU/μg) of hydroxyproline (OHPro) in kidney between 10 and 30 mo, and from 9.7 ± 1.2 to 310.6 ± 34.6 AU/μg OHPro in the abdominal aorta. Food restriction reduced AGE accumulation to 21.4 ± 3.3 and 74.6 ± 16.5 AU/μg OHPro in kidney and aorta of 30-mo-old animals. Similar results were found for collagen prepared from isolated glomeruli (7.8 ± 1.2, 81.2 ± 16.1, and 10.3 ± 4.3 AU/μg OHPro in 10-mo, 30-mo, and restricted 30-mo-old rats). Reduction of intrarenal and arterial AGE accumulation by food restriction was confirmed by immunostaining in optical microscopy. Age-related changes in arterial and kidney structures as polyuria and proteinuria were mainly prevented by food restriction. These data indicate that chronic food restriction reduces the accumulation of AGE and preserves the structure and function of the renal and cardiovascular systems in learn rats, although it did not affect survival of the animals between 10 and 30 mo.
Length of Stay and Costs for Hospitalized Hemodialysis Patients
Authors: KSHIRSAGAR ABHIJIT V. , HOGAN SUSAN L. , MANDELKEHR LARRY , FALK RONALD J. 
Published: April 2021

Abstract.
The high cost of hospitalization for hemodialysis patients has become a major health care issue. To address this issue, length of hospital stay and costs for these patients were compared with services covered by nephrologists and services covered by internists. Hemodialysis patients (n = 161) were prospectively admitted 219 times on alternate days to services covered by nephrologists or by internists from July 1995 to March 1996. Admissions to nonmedical services and admissions for overnight observation were excluded. Length of stay, costs, and risk-adjusted predicted length of stay and costs, as well as the number of consultations were compared between services, using Wilcoxon rank sum tests. Readmissions and deaths were compared using χ2 tests. Mean length of stay for admissions to the nephrology service (n = 114) was 6.3 days compared with 8.1 days for admissions to internal medicine services (n = 105) (P = 0.017). The predicted length of stay was similar. Mean overall cost for admissions under the care of nephrologists was $7,925 versus $10,773 under the care of internists (P = 0.101). The internal medicine service averaged 1.5 consultations versus 0.5 consultations for the nephrology service (P = 0.001). The risk of readmission was 24% for nephrologists and 30% for internists (P = 0.328). Death within 90 days of discharge was 12% for the nephrology group and 22% for the internal medicine group (P = 0.07). The length of stay was significantly shorter for hemodialysis patients under the care of nephrologists compared with internists. The average total costs and risk of readmissions tended to be lower for nephrologists. If these results are corroborated, the care of hemodialysis patients by the nephrologist could diminish the overall expense of the ESRD program.
STUDI PERBANDINGAN KINERJA SIMPANG BERSINYAL DI JALAN DR RADJIMAN KOTA SURAKARTA MENGGUNAKAN METODE MKJI 1997 DAN PERANGKAT LUNAK PTV VISTRO
Authors: Putri Rizki Dewayani , Yulianto Budi , Setiono Setiono 
Published: April 2021

<p>Pada tahun 2016, di Jalan Dr. Radjiman diberlakukan jalan satu arah. Kemudian pada tahun 2018, arus di Jalan Dr Radjiman berubah dari satu arah menjadi dua arah yang menyebabkan Dishub Solo menambah rambu-rambu untuk menginformasikan kepada pengguna jalan yaitu diperlukan rambu lalu lintas dan Alat Pemberi Isyarat Lalu Lintas (APILL) untuk mengatur perilaku kendaraan saat berada di persimpangan agar konflik-konflik yang terjadi bisa dihindari.</p><p>Penelitian ini bertujuan untuk mengetahui kinerja simpang yaitu Simpang Bhayangkara (Jalan Dr Radjiman - Jalan Bhayangkara) dan Simpang Baron (Jalan Dr. Radjiman – Jalan Dr Wahidin serta Jalan Batik Keris) berdasarkan metode MKJI 1997 dengan skenario yang dibuat, membandingkan hasil panjang antrian dari hasil analisis metode MKJI 1997 dengan data lapangan, mengetahui kinerja simpang berdasarkan metode HCM 2010 (PTV Vistro) dengan skenario yang dibuat, serta membandingkan hasil panjang antrian dari hasil analisis metode HCM 2010 (PTV Vistro) dengan data lapangan.</p><p>Dari analisis metode MKJI 1997 kinerja simpang bersinyal dalam kondisi stabil untuk panjang antrian Skenario Gati 3 adalah skenario yang mendekati lapangan. Dalam HCM 2010 (PTV Vistro), kinerja simpang bersinyal dalam kondisi tidak stabil, untuk panjang antrian Skenario Gati 3 memiliki besaran nilai panjang antrian yang mendekati dengan data di lapangan. Tundaan dari MKJI 1997 dan PTV Vistro memiliki perbedaan yang signifikan.</p><p> </p>
ANALISIS KAPASITAS DRAINASE SEBAGAI UPAYA PENGENDALIAN BANJIR DI KELURAHAN SANGKRAH, SURAKARTA
Authors: Sholi Imam Nor , Hadiani Raden Roro Rintis , Suryandari Endah Sitaresmi 
Published: April 2021

<p>Kelurahan Sangkrah berada di Kecamatan Pasar Kliwon Kota Surakarta. Kelurahan Sangkrah dilewati oleh Sungai Pepe Hilir dan Kali Jenes. Pada bantaran sungai sering terjadi banjir dan genangan. Salah satu cara untuk upaya pengendalian banjir adalah dengan menganalisis sistem kerja drainase di Kelurahan Sangkrah. Analisis sistem drainase dihitung dengan metode Hidrograf Satuan Sintesis <em>Soil Conservation Service</em>. Analisis flood routing dilakukan dengan <em>software </em>HEC-RAS dengan aliran <em>unsteady flow</em>. Dari hasil pemetaan itu didapatkan volume banjir yang diolah dengan excel. Sedangkan debit puncak saluran drainase dihitung dengan rumus manning.</p><p>Hasil analisis penelitian menunjukkan bahwa volume banjir yang melimpah dari Sungai Pepe Hilir akibat Q5 sebesar 1943,7 m3/jam, akibat Q10 adalah sebesar 2714,1 m3/jam, akibat Q25 sebesar 3278,4 m3/jam, dan akibat Hujan dua harian maksimum adalah sebesar 8795,8 m3/jam. Drainase yang direncanakan dalam keadaan normal memiliki kapasitas tampung sebesar 1013066,96 m3/jam dari hasil tersebut dapat disimpulkan bahwa dimensi saluran drainase rencana dapat menampung volume banjir yang terjadi pada periode ulang 5 tahun, 10 tahun, 25 tahun, dan hujan 2 harian.</p>