bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of High Extracellular Phosphate Concentration on Arachidonic Acid Production by Parathyroid Tissue In Vitro
Authors: ALMADÉN YOLANDA , CANALEJO ANTONIO , BALLESTEROS EVARISTO , AN[Combining Tilde]ÓN GRACIA , RODRÍGUEZ MARIANO
Published: April 2021

Recent in vivo and in vitro studies show that high phosphate directly stimulates parathyroid hormone (PTH) secretion. However, little is known about the intracellular signaling system involved in the regulation of PTH secretion by extracellular phosphate. High extracellular calcium is coupled to the activation of phospholipase A2 (PLA2) and the formation of arachidonic acid (AA), a potent inhibitor of PTH release. The present study was designed to evaluate whether a high phosphate concentration has an effect on the PLA2-AA pathway in parathyroid cells. In vitro experiments were performed in parathyroid tissue obtained from normal rats and dogs. AA production was measured in parathyroid tissue in response to 1- and 4-mM phosphate concentration and after addition of PLA2 to the medium. To determine whether the effect of phosphate on AA production in parathyroid cells was tissue specific, separate experiments were performed to test the effect of phosphate in rat adrenal glomerulosa cells, which are known to increase AA production in response to angiotensin II. The effect of sulfate, an ion with chemical characteristics similar to phosphate, on PTH secretion was also evaluated. In parathyroid tissue, a high phosphate concentration decreased the high calcium-induced AA production. This effect of phosphate was associated with an increase in PTH secretion. The addition of AA reversed the stimulatory effect of phosphate on PTH secretion. In another type of AA-responsive tissue, the adrenal glomerulosa, a high phosphate concentration did not affect the production of AA when stimulated by angiotensin II. In a normal phosphate concentration, the addition of PLA2 stimulated AA production and decreased the PTH secretion. However, in a 4-mM phosphate concentration, the addition of PLA2 did not reduce PTH secretion and did not stimulate AA production. Finally, sulfate did not affect PTH secretion. In conclusion, a high phosphate concentration affects the production of AA by parathyroid tissue. This effect of phosphate may be the mechanism by which a high phosphate concentration stimulates PTH secretion.
Posttransplantation Relapse of FSGS Is Characterized by Glomerular Epithelial Cell Transdifferentiation
Authors: BARIÉTY JEAN , BRUNEVAL PATRICK , HILL GARY , IRINOPOULOU THEANO , MANDET CHANTAL , MEYRIER ALAIN
Published: April 2021

This study examined six cases of idiopathic nephrotic syndrome with primary lesions of focal segmental glomerulosclerosis (FSGS) that relapsed after renal transplantation. The glomerular lesions comprised the cellular, the collapsing, and the scar variants of FSGS and showed shedding of large round cells into Bowman's space and within the tubular lumens. Immunohistochemistry and confocal laser microscopy carried out on kidneys with FSGS relapse disclosed several phenomena. (1) Some podocytes that expressed podocalyxin, synaptopodin, and glomerular epithelial protein-1 were detached from the tuft and were free in the urinary space. (2) In the cellular variant, most podocytes had lost podocyte-specific epitopes (podocalyxin, synaptopodin, glomerular epithelial protein-1, Wilm's tumor protein-1, complement receptor-1, and vimentin). In the scar variant, these podocyte markers were absent from cobblestone-like epithelial cells and from pseudotubules. (3) Podocytes had acquired expression of various cytokeratins (CK; identified by the AE1/AE3, C2562, CK22, and AEL-KS2 monoclonal antibodies) that were not found in the podocytes of control glomeruli. Parietal epithelial cells expressed AE1/AE3 CK that were faintly, if ever, found on the parietal epithelial cells of normal glomeruli. (4) Numerous cells located at the periphery of the tuft or free in Bowman's space and within tubular lumens expressed macrophagic epitopes (identified by PGM1 [CD68], HAM56, and 25F9 monoclonal antibodies). These macrophage-like cells expressed the activation epitopes HLA-DR and CD16. (5) A number of these cells coexpressed podocalyxin + AE1/AE3 CK, podocalyxin + CD68, and CD68 + AE1/AE3. These findings suggest that in primary FSGS relapsing on transplanted kidneys, some “dysregulated” podocytes, occasionally some parietal epithelial cells, and possibly some tubular epithelial cells undergo a process of transdifferentiation. This process of transdifferentiation was especially striking in podocytes that acquired macrophagic and CK epitopes that are absent from normal adult and fetal podocytes.
Renal Interstitial Fibrosis Is Reduced in Angiotensin II Type 1a Receptor-Deficient Mice
Authors: SATOH MINORU , KASHIHARA NAOKI , YAMASAKI YASUSHI , MARUYAMA KEISUKE , OKAMOTO KAZUNORI , MAESHIMA YOUHEI , SUGIYAMA HITOSHI , SUGAYA TAKESHI , MURAKAMI KAZUO , MAKINO HIROFUMI
Published: April 2021

Unilateral ureteral obstruction (UUO) results in tubulointerstitial fibrosis of the affected kidney by stimulating the renin-angiotensin system. This study established a UUO model in angiotensin type 1a receptor (AT1a) deficient (mutant) mice to elucidate the role of angiotensin II through AT1a on the fibrosis of the obstructed kidney (OBK). The relative volume of the tubulointerstitium was measured by an image analyzer; deposition of collagen types III and IV and monocyte/macrophage infiltration were histologically examined using specific antibodies. Also determined were the mRNA levels of transforming growth factor-β by Northern blot analysis. Nuclear factor-κB activity was assessed by gel shift assay. UUO in wild mice resulted in a marked expansion of relative volume of the tubulointerstitium, together with increased deposition of collagen types III and IV and number of infiltrated monocytes/macrophages in the interstitium, relative to sham-operated mice. In comparison, these changes were significantly lower in mutant mice with UUO. The mRNA level of transforming growth factor-β was significantly higher in the OBK of wild mice with UUO compared with sham-operated mice. In contrast, the increase in mRNA level in the OBK of mutant mice was significantly less than in wild mice. Finally, UUO resulted in activation of nuclear factor-κB in wild mice but was inhibited in the OBK of mutant mice. The results provide direct evidence that angiotensin II acting via the AT1a plays a pivotal role in the development of tubulointerstitial fibrosis in UUO.
Impact of Dialysis Adequacy on the Mortality and Morbidity of Anuric Chinese Patients Receiving Continuous Ambulatory Peritoneal Dialysis
Authors: SZETO CHEUK-CHUN , WONG TERESA YUK-HWA , CHOW KAI-MING , LEUNG CHI-BON , LAW MAN-CHING , WANG ANGELA YEE-MOON , LUI SIU-FAI , LI PHILIP KAM-TAO
Published: April 2021

Dialysis adequacy has a major impact on the outcome of continuous ambulatory peritoneal dialysis (CAPD) patients. However, most studies on peritoneal dialysis adequacy have focused on patients with significant residual renal function. The present study examined the effect of dialysis adequacy on anuric CAPD patients. A single-center prospective observational study on 140 anuric CAPD patients was performed. These patients were followed for 22.0 ± 11.9 mo. Dialysis adequacy and nutritional indices, including Kt/V, creatinine clearance (CCr), protein equivalent nitrogen appearance, percentage of lean body mass, and serum albumin level were monitored. Clinical outcomes included actuarial patient survival, technique survival, and duration of hospitalization. In the study population, 64 were male, 36 (25.7%) were diabetic, and 59 (42.1%) were treated with 6 L exchanges per day. The body weight was 59.2 ± 10.2 kg. Average Kt/V was 1.72 ± 0.31, and CCr was 43.7 ± 11.5 L/wk per 1.73m2. Two-yr patient survival was 68.8%, and technique survival was 61.4%. Multivariate analysis showed that DM, duration of dialysis before enrollment, serum albumin, and index of dialysis adequacy (Kt/V or CCr) were independent factors of both patient survival and technique survival. It was estimated that for two patients who differed only in weekly Kt/V, a 0.1 higher value was associated with a 6% decrease in the RR of death (P < 0.05; 95% confidence interval, 0.92 to 0.99). Serum albumin and CCr were the only independent factors that predicted hospitalization. It was found that even when there is no residual renal function, higher dialysis dosage is associated with better actuarial patient survival, better technique survival, and shorter hospitalization. Dialysis adequacy has a significant impact on the clinical outcome of CAPD patients, and the beneficial effect is preserved in anuric patients as well as in an ethnic group that has a low overall mortality.
L-Arginine Supplementation Improves Function and Reduces Inflammation in Renal Allografts
Authors: VOS INGRID H. C. , RABELINK TON J. , DORLAND BERT , LOOS REMKO , MIDDELAAR BEN VAN , GRO[Combining Diaeresis]NE HERMANN-JOSEF , JOLES JAAP A.
Published: April 2021

Recovery from ischemia/reperfusion and immune-mediated injury in the renal transplant is associated with reduced renal hemodynamics and increased leukocyte infiltration. In diverse models of renal failure, L-arginine supplementation improved hemodynamics and reduced inflammation. However in a proinflammatory environment, L-arginine can worsen renal injury. This study investigated the therapeutic potential of L-arginine supplementation in allogeneic renal transplantation: Brown Norway rat kidneys were transplanted into Lewis rat recipients, with one native kidney remaining. Recipients received low-dose cyclosporin A (2.5 mg/kg per d subcutaneously) to obtain moderate vascular and interstitial rejection, with or without 1% L-arginine in drinking water for 7 d posttransplantation. Transplantation increased renal vasoconstriction (from 16.9 ± 1.33 to 35.1 ± 8.6 units; P < 0.01), thereby reducing GFR (from 0.96 ± 0.09 to 0.48 ± 0.10 ml/min; P < 0.05). Treatment with L-arginine restored renal graft function to levels found in normal donors (renal vascular resistance, 15.7 ± 1.69 units; GFR, 0.80 ± 0.06 ml/min). L-arginine significantly reduced vascular occlusion because of less inflammation, endothelial disruption, and thrombosis. L-arginine also decreased tubulitis, interstitial injury, and macrophage infiltration. These protective effects suggest that L-arginine might be useful as additive therapy to conventional immune suppression.
Oxidized LDL Suppresses NF-κB and Overcomes Protection from Apoptosis in Activated Endothelial Cells
Authors: HEERMEIER KATHRIN , LEICHT WOLFGANG , PALMETSHOFER ALOIS , ULLRICH MARKUS , WANNER CHRISTOPH , GALLE JAN
Published: April 2021

Atherosclerosis is a chronic inflammatory disease associated with enhanced apoptotic cell death in vascular cells, partly induced by oxidized low-density lipoprotein (OxLDL). However, proinflammatory stimuli such as lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α) activate endothelial cells (EC) and inhibit apoptosis through induction of nuclear factor κB (NF-κB)-dependent genes. This study therefore investigated whether OxLDL or its component, lysophosphatidylcholine (LPC), interacts with the effect of LPS or TNF-α on cell survival. Human EC were incubated with LPS, TNF-α, OxLDL, or LPC alone or in combinations. OxLDL (100 to 200 μg/ml) and LPC (100 to 300 μM) induced apoptosis dose-dependently. LPS and TNF-α had no effect on cell survival in the presence or absence of OxLDL or LPC. LPS and TNF-α both induced the antiapoptotic gene A20, whereas OxLDL and LPC suppressed its induction. Expression of A20 is regulated by NF-κB. OxLDL and LPC dose-dependently suppressed NF-κB activity. For functional analysis, bovine EC were transfected with A20 encoding expression constructs in sense and antisense orientation. Bovine EC that overexpressed A20 were protected against OxLDL-induced apoptosis, whereas expression of antisense A20 rendered cells more sensitive to OxLDL. These results suggest that OxLDL not only induces cell death, as has been shown before, but also compromises antiapoptotic protection of activated EC. OxLDL sensitizes EC to apoptotic triggers by interfering with the induction of A20 during the inflammatory response seen in atherosclerotic lesions. This inhibition is based on repression of NF-κB activation. The effect may be caused by the OxLDL component LPC.
Galectin-3 Modulates Ureteric Bud Branching in Organ Culture of the Developing Mouse Kidney
Authors: BULLOCK SIMON L. , JOHNSON TANYA M. , BAO QI , HUGHES R. COLIN , WINYARD PAUL J. D. , WOOLF ADRIAN S.
Published: April 2021

Galectin-3 is a mammalian β-galactoside—specific lectin with functions in cell growth, adhesion, and neoplastic transformation. On the basis of expression patterns in humans, it is proposed that galectin-3 modulates fetal collecting duct growth. This article provides evidence that galectin-3 can modulate branching morphogenesis of the mouse ureteric bud/collecting duct lineage. With the use of immunohistochemistry, galectin-3 was not detected in early metanephrogenesis but was upregulated later in fetal kidney maturation when the protein was prominent in basal domains of medullary collecting ducts. Addition of galectin-3 to embryonic days 11 and 12 whole metanephric cultures inhibited ureteric bud branching, whereas galectin-1 did not perturb morphogenesis, nor did a galectin-3 mutant lacking wild-type high-affinity binding to extended oligosaccharides. Exogenous galectin-3 retarded conversion of renal mesenchyme to nephrons in whole metanephric explants but did not affect nephron induction by spinal cord in isolated renal mesenchymes. Finally, addition of a blocking antiserum to galectin-3 caused dilation and distortion of developing epithelia in embryonic day 12 metanephroi cultured for 1 wk. The upregulation of galectin-3 protein during kidney maturation, predominantly at sites where it could mediate cell/matrix interactions, seems to modulate growth of the ureteric tree.
Collecting Duct Is a Site of Sodium Retention in PAN Nephrosis
Authors: DESCHE[Combining Circumflex Accent]NES GEORGES , WITTNER MONIKA , STEFANO ANTONIO DI , JOUNIER SYLVIE , DOUCET ALAIN
Published: April 2021

Micropuncture studies of the distal nephron and measurements of Na,K-ATPase activity in microdissected collecting tubules have suggested that renal retention of sodium in puromycin aminonucleoside (PAN) nephrotic rats originates in the collecting duct. The present study demonstrated this hypothesis by in vitro microperfusion and showed that amiloride was able to restore sodium balance. Indeed, isolated perfused cortical collecting ducts from PAN-treated rats exhibited an abnormally high transepithelial sodium reabsorption that was abolished by amiloride, and in vivo administration of amiloride fully prevented decreased urinary sodium excretion and positive sodium balance in nephrotic rats. As expected from the aldosterone independence of Na+ retention in PAN nephrotic rats, blockade of aldosterone receptor by potassium canrenoate did not alter urinary Na+ excretion, Na+ balance, or ascites formation in PAN nephrotic rats.
Verocytotoxin-Induced Apoptosis of Human Microvascular Endothelial Cells
Authors: PIJPERS ANTONETTA H. J. M. , SETTEN PETRA A. VAN , HEUVEL LAMBERTUS P. W. J. VAN DEN , ASSMANN KAREL J. M. , DIJKMAN HENDRIKUS B. P. M. , PENNINGS ARIE H. M. , MONNENS LEO A. H. , HINSBERGH VICTOR W. M. VAN
Published: April 2021

The pathogenesis of the epidemic form of hemolytic uremic syndrome is characterized by endothelial cell damage. In this study, the role of apoptosis in verocytotoxin (VT)-mediated endothelial cell death in human glomerular microvascular endothelial cells (GMVEC), human umbilical vein endothelial cells, and foreskin microvascular endothelial cells (FMVEC) was investigated. VT induced apoptosis in GMVEC and human umbilical vein endothelial cells when the cells were prestimulated with the inflammatory mediator tumor necrosis factor-α (TNF-α). FMVEC displayed strong binding of VT and high susceptibility to VT under basal conditions, which made them suitable for the study of VT-induced apoptosis without TNF-α interference. On the basis of functional (flow cytometry and immunofluorescence microscopy using FITC-conjugated annexin V and propidium iodide), morphologic (transmission electron microscopy), and molecular (agarose gel electrophoresis of cellular DNA fragments) criteria, it was documented that VT induced programmed cell death in microvascular endothelial cells in a dose- and time-dependent manner. Furthermore, whereas partial inhibition of protein synthesis by VT was associated with a considerable number of apoptotic cells, comparable inhibition of protein synthesis by cycloheximide was not. This suggests that additional pathways, independent of protein synthesis inhibition, may be involved in VT-mediated apoptosis in microvascular endothelial cells. Specific inhibition of caspases by Ac-Asp-Glu-Val-Asp-CHO, but not by Ac-Tyr-Val-Ala-Asp-CHO, was accompanied by inhibition of VT-induced apoptosis in FMVEC and TNF-α-treated GMVEC. These data indicate that VT can induce apoptosis in human microvascular endothelial cells.
Effects of Losartan and Amlodipine on Intrarenal Hemodynamics and TGF-β1 Plasma Levels in a Crossover Trial in Renal Transplant Recipients
Authors: IN[Combining Tilde]IGO PABLO , CAMPISTOL JOSEP M. , LARIO SERGIO , PIERA CARLOS , CAMPOS BEGON[Combining Tilde]A , BESCÓS MÓNICA , OPPENHEIMER FEDERICO , RIVERA FRANCISCA
Published: April 2021

Hypertension and hyperfiltration are two important risk factors for the development of chronic allograft nephropathy. Transforming growth factor-β1 (TGF-β1) is the main cytokine involved in the fibrotic process that is involved in chronic rejection. Angiotensin II upregulates TGF-β1 production. Angiotensin II receptor antagonists therefore could not only control BP but also reduce TGF-β1 production in renal transplant patients. The aim of this study was to compare the effects of losartan and amlodipine on renal hemodynamics, as well as TGF-β1 and endothelin-1 (ET-1) plasma levels in a group of renal transplant patients who had normal renal function and who were treated with cyclosporine. Seventeen renal transplant patients who were receiving cyclosporine and who had normal graft function were included in a random 2 × 2 crossover trial with amlodipine and losartan (6 wk with each therapy). Three studies were performed (at baseline and at the end of both treatment periods) to determine renal hemodynamics, TGF-β1, and ET-1. Both treatments controlled BP to a similar degree, but only amlodipine increased GFR through an increase in the estimated glomerular hydrostatic pressure and filtration fraction. In contrast, losartan maintained GFR and reduced estimated glomerular hydrostatic pressure and filtration fraction significantly. Losartan and amlodipine had opposite effects on TGF-β1. Amlodipine did not affect TGF-β1 concentrations. In contrast, losartan reduced the plasma levels of TGF-β1 by approximately by 50% (from baseline, 5.2 to 2.6 ng/ml; P = 0.01); the majority of the patients reached normal levels of TGF-β1. ET-1 concentrations were significantly higher during amlodipine compared with losartan treatment. The present study documents that with similar control of BP, losartan and amlodipine have opposite effects on renal hemodynamics and on TGF-β1 concentrations. These differences could be important for the management of chronic allograft nephropathy.
Diabetes Insipidus in Uricase-Deficient Mice: A Model for Evaluating Therapy with Poly(Ethylene Glycol)-Modified Uricase
Authors: KELLY SUSAN J. , DELNOMDEDIEU MARIELLE , OLIVERIO MICHAEL I. , WILLIAMS DAVID L. , SAIFER MARK G. P. , SHERMAN MERRY R. , COFFMAN THOMAS M. , JOHNSON ALLAN G. , HERSHFIELD MICHAEL S.
Published: April 2021

Uricase-deficient mice develop uric acid nephropathy, with high mortality rates before weaning. Urate excretion was quantitated and renal function was better defined in this study, to facilitate the use of these mice as a model for evaluating poly(ethylene glycol)-modified recombinant mammalian uricases (PEG-uricase) as a potential therapy for gout and uric acid nephropathy. The uric acid/creatinine ratio in the urine of uricase-deficient mice ranges from 10 to >30; on a weight basis, these mice excrete 20- to 40-fold more urate than do human subjects. These mice consistently develop a severe defect in renal concentrating ability, resulting in an approximately sixfold greater urine volume and a fivefold greater fluid requirement, compared with normal mice. This nephrogenic diabetes insipidus leads to dehydration and death of nursing mice but, with adequate water replacement, high urine flow protects adults from progressive renal damage. Treatment of uricase-deficient mice with PEG-uricase markedly reduced urate levels and, when initiated before weaning, preserved the renal architecture (as evaluated by magnetic resonance micros-copy) and prevented the loss of renal concentrating function. PEG-uricase was far more effective and less immunogenic than unmodified uricase. Retention of uricase in most mammals and its loss in humans and some other primates may reflect the evolution of renal function under different environmental conditions. PEG-uricase could provide an effective therapy for uric acid nephropathy and refractory gout in human patients.
Chemokine and Chemokine Receptor Expression during Initiation and Resolution of Immune Complex Glomerulonephritis
Authors: ANDERS HANS-JOACHIM , VIELHAUER VOLKER , KRETZLER MATTHIAS , COHEN CLEMENS D. , SEGERER STEPHAN , LUCKOW BRUNO , WELLER LARS , GRÖNE HERMANN-JOSEF , SCHLÖNDORFF DETLEF
Published: April 2021

Chemokines participate in leukocyte infiltration, which plays a major role in glomerular injury during immune complex glomerulonephritis (IC-GN). Because target cell expression of chemokine receptors (CCR) is thought to mediate leukocyte migration, the expression pattern of chemokines and CCR in a model of IC-GN was examined. The transient course and predominant glomerular pathology of this model allows the examination of both the induction and resolution phases of IC-GN. GN was induced in mice by daily apoferritin injection for 2 wk. Urine samples and kidneys were obtained at 1, 2, and 4 wk. Albuminuria was noted at 2 wk, but resolved after 4 wk. This was associated with glomerular IC deposits and mesangial proliferation. Glomerular macrophage infiltration was prominent at 1 and 2 wk, which resolved at 4 wk. Expression of monocyte chemoattractant protein-1 (MCP-1) and RANTES mRNA was upregulated at week 1 and decreased to control levels at weeks 2 and 4. The expression was localized to glomeruli by in situ hybridization and immunohistochemistry. The mRNA of CCR1, CCR2, and CCR5 but not CCR3 or CCR4 were upregulated at week 1 and decreased at weeks 2 and 4. Expression of CCR5 was located to the glomerulus by in situ hybridization and quantitative reverse transcription-PCR of isolated glomeruli. In summary, in a model of transient IC-GN, MCP-1 and RANTES and their receptors CCR1, CCR2, and CCR5 are expressed early and are already downregulated at the peak of proteinuria and leukocyte infiltration. Resolution of glomerulonephritis is associated with a return to baseline of chemokine and CCR expression. Therefore, it is concluded that glomerular MCP-1 and RANTES production directs circulating leukocytes that express CCR1, CCR2, and CCR5 into the glomerulus. After initiating GN, MCP-1 and RANTES and their receptors are readily downregulated.
Blocking Angiotensin II Synthesis/Activity Preserves Glomerular Nephrin in Rats with Severe Nephrosis
Authors: BENIGNI ARIELA , TOMASONI SUSANNA , GAGLIARDINI ELENA , ZOJA CARLA , GRUNKEMEYER JAMES A. , KALLURI RAGHU , REMUZZI GIUSEPPE
Published: April 2021

Angiotensin-converting enzyme inhibitors restore size-selective dysfunction of the glomerular barrier in experimental animals and humans with proteinuric nephropathies, although the structural and molecular determinants of such an effect are not completely understood. This study used an accelerated model of experimental nephrosis to assess nephrin gene and protein expression in the kidney and the possible modulating effect of drugs that block angiotensin II (AII) synthesis/activity. Passive Heymann nephritis (PHN) and control animals were studied at day 7, month 4, and month 8. Additional PHN rats were treated with lisinopril or AII receptor blocker L-158,809 and studied at 8 mo. Lisinopril and L-158,809 controlled BP, prevented proteinuria, and protected PHN animals from renal injury. An intense signal of nephrin mRNA was detected in glomeruli of control animals mainly restricted to podocytes. In PHN rats, nephrin staining progressively and remarkably decreased with time. Lisinopril and L-158,809 fully prevented the decrease in nephrin transcripts to levels comparable to those of control rats. Consistent with nephrin mRNA expression, immunostaining of the protein showed a progressive decrease in kidneys from PHN rats that was completely abolished by lisinopril and L-158,809. In summary, progressive renal injury was associated with downregulation of nephrin gene that was totally prevented by angiotensin-converting enzyme inhibitor and AII receptor blocker, suggesting that renoprotection afforded by drugs that interfere with AII synthesis/activity was related to an effect on nephrin assembly.
Electroporation-Mediated Gene Transfer that Targets Glomeruli
Authors: TSUJIE MICHIKO , ISAKA YOSHITAKA , NAKAMURA HIROYUKI , IMAI ENYU , HORI MASATSUGU
Published: April 2021

Electroporation has been applied to introducing DNA into several organs; however, gene expression was localized around the injected area. Examined was the efficiency of intrarenal injection of DNA followed by in vivo electroporation, using FITC-labeled oligodeoxynucleotides (FITC-ODN) and plasmid DNA expressing β-galactosidase or luciferase. FITC-ODN or expression vectors were injected into the left renal artery; thereafter, the left kidney was electroporated between a pair of tweezer-type electrodes. FITC-ODN were transferred into all glomeruli, and transfected cells were identified as mesangial cells. Four d after transfection of the pCAGGS-LacZ gene, β-galactosidase expression was observed in 75% of glomeruli. To compare the transfection efficacy by electroporation with that by the hemagglutinating virus of Japan (HVJ) liposome method, a luciferase reporter gene, pActLuc, was transferred into glomeruli by either electroporation or the HVJ liposome method. On day 4, electroporation resulted in higher glomerular luciferase activity than did the HVJ liposome method. We also observed that co-transfection of pcEBNA, an expression vector for Epstein-Barr virus nuclear antigen, and poriP-cLuc, oriP-harboring vector, resulted in an eightfold higher luciferase gene expression than simple poriP-cLuc. No histologic damages were seen in glomeruli or tubular epithelial cells. In conclusion, gene transfer into renal artery followed by electroporation was an effective and simple strategy for gene transfer that targets glomerular mesangial cells.
Cell Proliferation in the Loop of Henle in the Developing Rat Kidney
Authors: CHA JUNG-HO , KIM YOUNG-HEE , JUNG JU-YOUNG , HAN KI-HWAN , MADSEN KIRSTEN M. , KIM JIN
Published: April 2021

In the developing rat kidney, there is no separation of the medulla into an outer and inner zone. At the time of birth, ascending limbs with immature distal tubule epithelium are present throughout the renal medulla, all loops of Henle resemble the short loop of adult animals, and there are no ascending thin limbs. It was demonstrated previously that immature thick ascending limbs in the renal papilla are transformed into ascending thin limbs by apoptotic deletion of cells and transformation of the remaining cells into a thin squamous epithelium. However, it is not known whether this is the only source of ascending thin limb cells or whether cell proliferation occurs in the segment undergoing transformation. This study was designed to address these questions and to identify sites of cell proliferation in the loop of Henle. Rat pups, 1, 3, 5, 7, and 14 d old, received a single injection of 5-bromo-2′-deoxyuridine (BrdU) 18 h before preservation of kidneys for immunohistochemistry. Thick ascending and descending limbs were identified by labeling with antibodies against the serotonin receptor, 5-HT1A, and aquaporin-1, respectively. Proliferating cells were identified with an antibody against BrdU. BrdU-positive cells in descending and ascending limbs of the loop of Henle were counted and expressed as percentages of the total number of aquaporin-1—positive and 5-HT1A—positive cells in the different segments. In the developing kidney, numerous BrdU-positive nuclei were observed in the nephrogenic zone. Outside of this location, BrdU-positive tubule cells were most prevalent in medullary rays in the inner cortex and in the outer medulla. BrdU-labeled cells were rare in the papillary portion of the loop of Henle and were not observed in the lower half of the papilla after 3 d of age. BrdU-labeled nuclei were not observed in segments undergoing transformation or in newly formed ascending thin limb epithelium. It was concluded that the growth zone for the loop of Henle is located around the corticomedullary junction, and the ascending thin limb is mainly, if not exclusively, derived from cells of the thick ascending limb.
Impaired Angiogenesis in the Remnant Kidney Model
Authors: KANG DUK-HEE , JOLY ALISON H. , OH SE-WOONG , HUGO CHRISTIAN , KERJASCHKI DONTSCHO , GORDON KATHERINE L. , MAZZALI MARILDA , JEFFERSON J. ASHLEY , HUGHES JEREMY , MADSEN KIRSTEN M. , SCHREINER GEORGE F. , JOHNSON RICHARD J.
Published: April 2021

Few studies have examined the role of the microvasculature in progressive renal disease. It was hypothesized that impaired angiogenesis might occur in the diseased kidney and could contribute to renal scarring. Progressive renal disease was induced in rats by 5/6 renal ablation and those rats were compared with sham-operated control animals at multiple time points, for examination of changes in the microvasculature and the expression of angiogenic factors. An early angiogenic response was documented in remnant kidneys, with increases in the proliferation of peritubular (1 wk) and glomerular (2 wk) endothelial cells. Subsequently, however, there was a decrease in endothelial cell proliferation, which was reduced to levels below those of sham-treated animals, in conjunction with interstitial expression of the antiangiogenic factor thrombospondin-1 (TSP-1) and decreased tubular expression of the proangiogenic factor vascular endothelial growth factor (VEGF). Both the increase in TSP-1 expression and the loss of VEGF expression were correlated with capillary loss and the development of glomerulosclerosis and interstitial fibrosis. Progressive macrophage infiltration was correlated both spatially and quantitatively with the sites of absent or diminished VEGF expression. In addition, macrophage-associated cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-α) inhibited VEGF mRNA expression and protein secretion by cultured tubular epithelial cells of the medullary thick ascending limb, under both normoxic and hypoxic conditions. Impaired angiogenesis characterizes the remnant kidney model and is correlated with progression. The impaired angiogenesis may be mediated by alterations in the renal expression of TSP-1 and VEGF, with the latter being regulated by macrophage-associated cytokines.
Long-Term Effects of Arterial Stenting on Kidney Functionfor Patients with Ostial Atherosclerotic Renal Artery Stenosis and Renal Insufficiency
Authors: BEUTLER JAAP J. , VAN AMPTING JACOBINE M. A. , VEN PETER J. G. VAN DE , KOOMANS HEIN A. , BEEK FREDERIK J. A. , WOITTIEZ AREND-JAN J. , MALI WILLEM P. T. M.
Published: April 2021

It is uncertain whether renal artery stent placement in patients with atherosclerotic renovascular renal failure can prevent further deterioration of renal function. Therefore, the effects of renal artery stent placement, followed by patency surveillance, were prospectively studied in 63 patients with ostial atherosclerotic renal artery stenosis and renal dysfunction (i.e., serum creatinine concentrations of >120 μmol/L (median serum creatinine concentration, 171 μmol/L; serum creatinine concentration range, 121 to 650 μmol/L). Pre-stent renal (dys) function was stable for 28 patients and declining for 35 patients (defined as a serum creatinine concentration increase of ≥20% in 12 mo). The median follow-up period was 23 mo (interquartile range, 13 to 29 mo). Angioplasty to treat restenosis was performed in 12 cases. Five patients reached end-stage renal failure within 6 mo, and this was related to stent placement in two cases. Two other patients died or were lost to follow-up monitoring within 6 mo, with stable renal function. For the remaining 56 patients, the treatment had no effect on serum creatinine levels if function had previously been stable; if function had been declining, median serum creatinine concentrations improved in the first 1 yr [from 182 μmol/L (135 to 270 μmol/L) to 154 μmol/L (127 to 225 μmol/L); P < 0.05] and remained stable during further follow-up monitoring. In conclusion, stent placement, followed by patency surveillance, to treat ostial atherosclerotic renal artery stenosis can stabilize declining renal function. For patients with stable renal dysfunction, the usefulness is less clear. The possible advantages must be weighed against the risk of renal failure advancement with stent placement.
Antineutrophil Cytoplasmic Autoantibody—Associated Glomerulonephritis in Children
Authors: HATTORI MOTOSHI , KURAYAMA HIDEAKI , KOITABASHI YASUSHI
Published: April 2021

A retrospective investigation was conducted by members of the Japanese Society for Pediatric Nephrology from 1990 to 1997 to define the clinical features and outcome of antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis in children. Thirty-four ANCA-seropositive Japanese pediatric patients with biopsy-proven pauci-immune necrotizing crescentic glomerulonephritis were identified. Of these, 3 cases associated with Wegener's granulomatosis were excluded because of the small sample size. Among the 31 patients studied, 10 had a diagnosis of necrotizing crescentic glomerulonephritis alone and 21 had microscopic polyangiitis. Females predominated (87%), and the median age at onset was 12 yr. Twenty-six patients received treatment with cyclophosphamide and corticosteroids, and five patients received treatment with corticosteroids alone; 84% of patients achieved remission, and 39% of responders relapsed in a median of 24 mo. ANCA titers correlated with response to treatment and disease activity, with some exceptions. Patients were followed for a median of 42 mo (range, 3 to 96 mo). Nine of 31 patients (29.0%) progressed to end-stage renal disease, 6 (19.4%) had reduced renal function, and 15 (48.4%) had normal renal function at the last observation. One patient (3.2%) died from cytomegalovirus infection 3 mo after initiation of therapy. Life-table analysis showed 75% renal survival at 39 mo. Patients who subsequently developed end-stage renal disease (n = 9) had significantly higher average peak serum creatinine levels and more chronic pathologic lesions at diagnosis compared with patients with favorable renal outcome (n = 15). In conclusion, our clinical experience suggests that the clinical disease spectrum of ANCA-associated glomerulonephritis is similar in pediatric and adult patients, but there is a female predominance in children.
Dynamic Changes of the Total Pore Area Available for Peritoneal Exchange in Children
Authors: FISCHBACH MICHEL , HARALDSSON BO[Combining Diaeresis]RJE
Published: April 2021

The most important of the parameters that describe exchange across the peritoneal membrane is the total pore area over diffusion distance (A0/Δx). It determines the rate of diffusion and mainly seems to reflect the number of capillaries available for exchange. In the present study, a simplified three-pore analysis was used to estimate A0/Δx from peritoneal equilibration tests. Two groups of children (mean age, 9.5 yr) who were on chronic peritoneal dialysis underwent studies with peritoneal equilibration tests. In the first group of children, three levels of fill volumes were used in each patient. In the second group of patients, the effects of posture and dwell time were analyzed from four consecutive peritoneal dialysis samples obtained after 15, 30, 60, and 90 min. As the fill volume was raised from 800 to 1400 ml/m2 BSA, the steady-state A0/Δx increased significantly by 21%, i.e., from 19,900 ± 1200 to 24,000 ± 1450 cm2/cm per 1.73 m2 (n = 8). A further increase to 2000 ml/m2 did not result in any change of A0/Δx. Moreover, steady-state A0/Δx fell significantly when the patients were standing, 21,900 ± 1400 compared with 29,400 ± 1330 cm2/cm per 1.73m2 (n = 6) obtained in the supine position. There was a transient (<30 min) increase in A0/Δx initially during the dwell, probably reflecting vasodilation and recruitment of capillaries. It is concluded that factors such as the intraperitoneal fill volume, posture, and dwell time all dynamically affect the total pore area available for exchange.
Mutations in theCOL4A4 and COL4A3 Genes Cause Familial Benign Hematuria
Authors: Badenas Ce[Combining Grave Accent]lia , Praga Manuel , Tazón Bárbara , Heidet Laurence , Arrondel Christelle , Armengol Anna , Andrés Amado , Morales Enrique , Camacho Juan Antonio , Lens Xose , Dávila Sonia , Mila[Combining Grave Accent] Montse , Antignac Corinne , Darnell Alejandro , Torra Roser
Published: April 2021

Familial benign hematuria (FBH) is a common autosomal dominant disorder characterized by the presence of persistent or recurrent hematuria. The clinical and pathologic features of this syndrome resemble those of early Alport syndrome (AS), and for this reason a common molecular defect has been proposed. The COL4A3/4 genes seem to be involved in both autosomal AS and FBH. This study involves a linkage analysis for the COL4A3/4 loci and a search for mutations within these genes in 11 biopsy-proven FBH families. Haplotype analysis showed that linkage to the COL4A3/4 locus could not be excluded in eight of nine families. One family was not linked to this locus; however, it included three affected women who could be X-linked AS carriers. Two families were too small to perform linkage analysis. COL4A3 and COL4A4 mutation screening disclosed six new pathogenic mutations, two in the COL4A3 gene (G985V and G1015E) and four in the COL4A4 gene (3222insA, IVS23-1G>C, 31del11, and G960R). It is the first time that mutations within the COL4A3 gene are described in families with FBH. This study clearly demonstrates the main role of the COL4A4 and COL4A3 genes in the pathogenesis of FBH.
Race, Racism and Anthropology: Decolonising Health Inequality in a Time of Covid-19
Authors: Mullard Jordan Christina Ruth
Published: April 2021

In the United Kingdom, the government’s failure to consistently record the race and ethnicity of those who have died from COVID-19 and the disproportionate mortality impact of the virus on Black, Asian and Minority Ethnic (BAME) communities speaks to a systemic failure to account for the interplay between the social construction of race and the lived experience of racism, itself presented biologically as ‘poor health’. This failure has run for far longer and far deeper than many would care to admit. In this article, I use my own positionality as a ‘Mixed-Race Black’ woman to argue that the unique place of medical anthropology to sit at the intersection of the social, political, biological, and ecological means it can provide alternative approaches to understanding the disproportionate impacts of the pandemic and lay some foundations for repair strategies that encompass the patterns, processes, and constructs of health inequality.
Design of mechatronic engineering systems
in digitalized traditional and additive manufacturing
Authors: Kheifetz Mikhail L.
Published: April 2021

The paper presents the analysis of the steps and stages of designing process equipment for traditional manufacturing. The features of building process equipment using energy flows and consumables are studied. Structural synthesis of mechatronic systems in digitalized manufacturing make it possible to add new stages to the process of creating process equipment for both traditional automated subtractive and new additive manufacturing. The processes of manufacturing parts without forming equipment described by the algorithms according to the proposed structural diagram of connections provide an opportunity to analyze the existing equipment and develop new equipment for laminate synthesis of products.
The paper illustrates the use of methods and procedures for laminate synthesis and fabrication of parts from composite materials using process equipment based on the application of energy flows and material components for new additive and traditional subtractive manufacturing. Also, methods and diagrams for automation and computer-aided process control over product manufacturing are shown.
Downloading Viral Metagenome Data v1
Authors: Bolduc Benjamin
Published: April 2021

Downloading reads from the Ocean Sampling Day (2014) using fastq-dump, a tool from the SRA toolkit implemented in Cyverse.
O BRINCAR E O PRIMEIRO ANO DO ENSINO FUNDAMENTAL: UMA DELICADA RELAÇÃO DESCORTINADA PELAS PESQUISAS
Authors: Andreeta Tiago Efrem , Going Luana Carramillo
Published: April 2021

O brincar e o lúdico apresentam uma delicada relação com o ensino fundamental devido à dicotomia historicamente construída, que prevê a escola como um lugar exclusivo para a aprendizagem, contraditória à brincadeira. Os termos são, assim, utilizados com semelhança semântica, embora o segundo tenha um sentido mais amplo, que abarca dentro de si o primeiro. O objetivo deste trabalho é verificar de que maneira as práticas docentes atuais permitem a presença do lúdico, necessário ao desenvolvimento do imaginário infantil nas turmas de primeiro ano do ensino fundamental. Para tal, realiza-se levantamento bibliográfico por meio de acesso às plataformas online da Biblioteca Digital Brasileira de Teses e Dissertações (BDTD), Banco de Teses e Dissertações da CAPES e Google Acadêmico, com o uso das palavras-chave “lúdic*”; “lúdic*”+“primeiro ano do ensino fundamental”; “brincar”+“primeiro ano do ensino fundamental”; “ludic*”+“ensino fundamental”. Os resultados observam que as pesquisas focam ora na perspectiva dos professores, ora na dos alunos para compreender como é permitido às crianças brincar dentro das escolas. O ponto convergente entre eles é a pouca utilização de brincadeiras e de momentos lúdicos em turmas de primeiro ano, ainda que as pesquisas o apresentem como parte importante do desenvolvimento infantil. Como justificativa para a ausência do lúdico no processo da aprendizagem as pesquisas atribuem dois pontos relevantes, sendo a pouca exploração sobre o tema durante a formação docente e a necessidade de trabalhar massivamente os conteúdos escolares impostos pela sociedade e pelos documentos emitidos por instituições oficiais, tanto em esfera federal, quanto estadual e municipal. O encontro entre esses dois fatores reforça o uso de atividades mecânicas e muitas vezes sem sentido para as crianças.
ENTREVISTA COM O PROFESSOR DERMEVAL SAVIANI (UNICAMP)
Authors: Saviani Dermeval , Ferreira Liliana Soares , Araújo Osmar Hélio , De Medeiros Emerson Augusto
Published: April 2021

Em entrevista especial para esta edição, o Professor Dermeval Saviani, cuja obra é reconhecida nacional e internacionalmente, apresenta uma leitura da Pedagogia no Brasil. Detentor de diversos prêmios, entre eles “Doutor Honoris Causa” em universidades brasileiras, o Professor, com sua obra, contribui e aprofunda o estudo e a análise da educação e das políticas educacionais no país. Do mesmo modo, a Pedagogia Histórica-Crítica, descrita por Saviani, pode ser entendida como uma perspectiva contra-hegemônica para o trabalho pedagógico na escola pública, visando a contribuir para que os trabalhadores acessem uma escola que lhes permita compreender e agir na transformação social.
A QUESTÃO ECOLÓGICA, PANDEMIA DA SÍNDROME RESPIRATÓRIA AGUDA (COVID-19) E ELEMENTOS PARA SE REPENSAR A FORMAÇÃO PROFISSIONAL
Authors: Rodrigues Rogério
Published: April 2021

Este ensaio tem como objetivo analisar as interações entre natureza e cultura presentes nas interfaces que se estabelecem na questão ecológica, pandemia da síndrome respiratória aguda (COVID-19) e a formação profissional. O referido estudo se justifica ao analisar a formação profissional dos sujeitos para além da perspectiva do especialista na ciência disciplinar. O método de pesquisa se refere em compreender a pandemia de 2020 numa perspectiva da teoria crítica no sentido de discutir este acontecimento para além da ciência disciplinar. Isso se apresenta como forma de analisar as especificidades para o combate ao referido vírus em ruptura com a especialidade científica. A modernidade contemporânea reduz o conhecimento na informação midiática da sociedade do espetáculo que se apresenta como forma que limita ao sujeito pensar a dinâmica da realidade. O referido estudo se justifica ao compreendermos que a pandemia se trata da falta de resposta da modernidade perante a desarmonia que se consolida no consumo insustentável e extremo desequilíbrio na distribuição dos bens naturais do planeta. Conclui-se que ocorre uma falta de compreensão multidisciplinar da pandemia perante a complexidade do objeto, primordialmente, como problema social. Deste modo, a referida pandemia é algo que se apresenta como resultado direto da destruição da natureza em que o desequilíbrio e descontrole do ecossistema afetam diretamente os sujeitos que vivem em sociedade. Torna-se imprescindível compreender essa dinâmica nas relações entre a natureza e cultura na unidade como forma de oposição direta ao conhecimento instrumental. Torna-se de fundamental importância desalienar o sujeito no modo de vida instrumental que se distancia da compreensão radical dos conceitos de como os fenômenos naturais são afetados pelas desigualdades sociais. Esta falta de compreensão reproduz as injustiças na sociedade na incapacidade de viver em harmonia com a natureza e na distribuição dos bens produzidos coletivamente na sociedade.
O ENSINO E AS IMAGENS A PARTIR DA PEDAGOGIA DA SENSIBILIDADE: ENTRE O ENCANTAMENTO E A NECESSIDADE DE FORMAÇÃO CONTINUADA
Authors: Tamanini Paulo Augusto , Souza Maria do Socorro
Published: April 2021

O presente artigo aborda a aplicabilidade das imagens no Ensino na perspectiva da Pedagogia da Sensibilidade. Para tanto, optou-se por uma abordagem atravessada por um escopo teórico que baliza e defende práticas pedagógicas humanizadoras, responsivas de um olhar mais afinado aos sentimentos dos discentes (MARIO, 2012; MORAES, 2006; SAVIANI, 2009; FREIRE, 2005). Servindo-se do espoco teórico que tangencia a Pedagogia da Sensibilidade, o presente estudo se divide em dois grandes tópicos-chave. Primeiramente, para além de sublinhar a atual tendência pedagógica de levar em consideração a natureza, as emoções e as sensibilidades que implicam diretamente nos processos formativos, exemplifica-se e principia-se o treino dos sentidos visuais através do uso ou da aplicabilidade das imagens no Ensino. No segundo momento, evidencia-se a necessidade de formação continuada para que os professores possam se capacitar para leitura de imagens, como proposta prática da Pedagogia da Sensibilidade, uma vez que os conteúdos imagéticos lidam com as sensibilidades visuais, com as percepções e capacidades hermenêuticas.