Concentrations of strontium, barium, cadmium, copper, zinc, manganese, chromium, antimony, selenium, and lead in the liver and kidneys of dogs according to age, gender, and the occurrence of chronic kidney disease

PubMed Central

Mainzer, Barbara; Lahrssen-Wiederholt, Monika; Schafft, Helmut; Palavinskas, Richard; Breithaupt, Angele; Zentek, Jürgen

2015-01-01

This study was conducted to measure the concentrations of strontium (Sr), barium (Ba), cadmium (Cd), copper (Cu), zinc (Zn), manganese (Mn), chromium (Cr), antimony (Sb), selenium (Se), and lead (Pb) in canine liver, renal cortex, and renal medulla, and the association of these concentrations with age, gender, and occurrence of chronic kidney disease (CKD). Tissues from 50 dogs were analyzed using inductively coupled plasma mass spectrometry. Cu, Zn, and Mn levels were highest in the liver followed by the renal cortex and renal medulla. The highest Sr, Cd, and Se concentrations were measured in the renal cortex while lower levels were found in the renal medulla and liver. Female dogs had higher tissue concentrations of Sr (liver and renal medulla), Cd (liver), Zn (liver and renal cortex), Cr (liver, renal cortex, and renal medulla), and Pb (liver) than male animals. Except for Mn and Sb, age-dependent variations were observed for all element concentrations in the canine tissues. Hepatic Cd and Cr concentrations were higher in dogs with CKD. In conclusion, the present results provide new knowledge about the storage of specific elements in canine liver and kidneys, and can be considered important reference data for diagnostic methods and further investigations. PMID:25234328

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubatto Birri, Paolo N.; Perez, Roberto D.; Consejo Nacional de Investigaciones Cientificas y Tecnologicas

Arsenic (As) is one of the most abundant hazards in the environment and it is a human carcinogen. Related to excretory functions, the kidneys in humans, animal models or naturally exposed fauna, are target organs for As accumulation and deleterious effects. Previous studies carried out using X-ray fluorescence spectrometry by synchrotron radiation (SR-{mu}XRF) showed a high concentration of As in the renal cortex of chronically exposed rats, suggesting that this is a suitable model for studies on renal As accumulation. This accumulation was accompanied by a significant increase in copper (Cu) concentration. The present study focused on the localization ofmore » these elements in the renal cortex and their correlation with physiological and histological As-related renal effects. Experiments were performed on nine male Wistar rats, divided into three experimental groups. Two groups received 100 {mu}g/ml sodium arsenite in drinking water for 60 and 120 consecutive days, respectively. The control group received water without sodium arsenite (<50 ppb As). For histological analysis, 5-{mu}m-thick sections of kidneys were stained with hematoxylin and eosin. Biochemical analyses were used to determine concentrations of plasma urea and creatinine. The As and Cu mapping were carried out by SR-{mu}XRF using a collimated white synchrotron spectrum (300 {mu}mx300 {mu}m) on kidney slices (2 mm thick) showing As and Cu co-distribution in the renal cortex. Then, renal cortical slices (100 {mu}m thick) were scanned with a focused white synchrotron spectrum (30 {mu}mx30 {mu}m). Peri-glomerular accumulation of As and Cu at 60 and 120 days was found. The effects of 60 days of arsenic consumption were seen in a decreased Bowman's space as well as a decreased plasma blood urea nitrogen (BUN)/creatinine ratio. Major deleterious effects; however, were seen on tubules at 120 days of exposition. This study supports the hypothesis that tubular accumulation of As-Cu may have some bearing on the arsenic-associated nephrotoxicological process.« less

Reduced Insulin Receptor Expression Enhances Proximal Tubule Gluconeogenesis.

PubMed

Pandey, Gaurav; Shankar, Kripa; Makhija, Ekta; Gaikwad, Anil; Ecelbarger, Carolyn; Mandhani, Anil; Srivastava, Aneesh; Tiwari, Swasti

2017-02-01

Reduced insulin receptor protein levels have been reported in the kidney cortex from diabetic humans and animals. We recently reported that, targeted deletion of insulin receptor (IR) from proximal tubules (PT) resulted in hyperglycemia in non-obese mice. To elucidate the mechanism, we examined human proximal tubule cells (hPTC) and C57BL/6 mice fed with high-fat diet (HFD, 60% fat for 20 weeks). Immunoblotting revealed a significantly lower protein level of IR in HFD compare to normal chow diet (NCD). Furthermore, a blunted rise in p-AKT 308 levels in the kidney cortex of HFD mice was observed in response to acute insulin (0.75 IU/kg body weight, i.p) relative to NCD n = 8/group, P < 0.05). Moreover, we found significantly higher transcript levels of phosphoenolpyruvate carboxykinase (PEPCK, a key gluconeogenic enzyme) in the kidney cortex from HFD, relative to mice on NCD. The higher level of PEPCK in HFD was confirmed by immunoblotting. However, no significant differences were observed in cortical glucose-6-phosphatase (G6Pase) or fructose-1,6, bisphosphosphatase (FBPase) enzyme transcript levels. Furthermore, we demonstrated insulin inhibited glucose production in hPTC treated with cyclic AMP and dexamethasone (cAMP/DEXA) to stimulate gluconeogenesis. Transcript levels of the gluconeogenic enzyme PEPCK were significantly increased in cAMP/DEXA-stimulated hPTC cells (n = 3, P < 0.05), and insulin attenuated this upregulation Furthermore, the effect of insulin on cAMP/DEXA-induced gluconeogenesis and PEPCK induction was significantly attenuated in IR (siRNA) silenced hPTC (n = 3, P < 0.05). Overall the above data indicate a direct role for IR expression as a determinant of PT-gluconeogenesis. Thus reduced insulin signaling of the proximal tubule may contribute to hyperglycemia in the metabolic syndrome via elevated gluconeogenesis. J. Cell. Biochem. 118: 276-285, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

l-Methionine and silymarin: A comparison of prophylactic protective capabilities in acetaminophen-induced injuries of the liver, kidney and cerebral cortex.

PubMed

Onaolapo, Olakunle J; Adekola, Moses A; Azeez, Taiwo O; Salami, Karimat; Onaolapo, Adejoke Y

2017-01-01

We compared the relative protective abilities of silymarin and l-methionine pre-treatment in acetaminophen overdose injuries of the liver, kidney and cerebral cortex by assessing behaviours, antioxidant status, tissue histological changes and biochemical parameters of hepatic/renal function. Rats were divided into six groups of ten each; animals in five of these groups were pre-treated with oral distilled water, silymarin (25mg/kg) or l-methionine (2.5, 5 and 10mg/kg body weight) for 14days; and then administered intraperitoneal (i.p.) acetaminophen at 800mg/kg/day for 3days. Rats in the sixth group (normal control) received distilled water orally for 14days and then i.p. for 3days. Neurobehavioural tests were conducted 7days after last i.p treatment, and animals sacrificed on the 8th day. Plasma was assayed for biochemical markers of liver/kidney function; while sections of the liver, kidney and cerebral cortex were either homogenised for assay of antioxidant status or processed for histology. Acetaminophen overdose resulted in locomotor retardation, excessive self-grooming, working-memory impairment, anxiety, derangement of liver/kidney biochemistry, antioxidant imbalance, and histological changes in the liver, kidney and cerebral cortex. Administration of silymarin or increasing doses of l-methionine counteracted the behavioural changes, reversed biochemical indices of liver/kidney injury, and improved antioxidant activity. Silymarin and l-methionine also conferred variable degrees of tissue protection, on histology. Either silymarin or l-methionine can protect vulnerable tissues from acetaminophen overdose injury; however, each offers variable protection to different tissues. This study highlights an obstacle to seeking the 'ideal' protective agent against acetaminophen overdose. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Comparison of 1.5 and 3 T BOLD MR to study oxygenation of kidney cortex and medulla in human renovascular disease.

PubMed

Gloviczki, Monika L; Glockner, James; Gomez, Sabas I; Romero, Juan C; Lerman, Lilach O; McKusick, Michael; Textor, Stephen C

2009-09-01

Imaging of the kidney using blood oxygen level dependent MR presents a major opportunity to examine differences in tissue oxygenation within the cortex and medulla applicable to human disease. We sought to define the differences between regions within kidneys and to optimize selection of regions of interest for study with 1.5 and 3 Tesla systems. Studies in 38 subjects were performed under baseline conditions and after administration of furosemide intravenously to examine changes in R2* as a result of suppressing oxygen consumption related to medullary tubular solute transport. These studies were carried out in patients with atherosclerotic renal artery stenosis (n = 24 kidneys) or essential hypertension or nonstenotic kidneys (n = 39). All patients but one were treated with agents to block the renin angiotensin system (ACE inhibitors or angiotensin receptor blockers). For each kidney, 3 levels (upper pole, hilum, and lower pole) were examined, including 3 individual segments (anterior, lateral, and posterior). Low basal R2* levels in kidney cortex (12.06 +/- 0.84 s(-1)) at 1.5 Tesla reflected robust blood flow and oxygenation and agreed closely with values obtained at 3.0 Tesla (13.62 +/- 0.56 s(-1), NS). Coefficients of variation ranged between 15% and 20% between segments and levels at both field strengths. By contrast, inner medullary R2* levels were higher at 3 T (31.66 +/- 0.74 s(-1)) as compared with 1.5 T (22.19 +/- 1.52 s(-1), P < 0.01). Medullary R2* values fell after furosemide administration reflecting reduced deoxyhemoglobin levels associated with blocked energy-dependent transport. The fall in medullary R2* at 3.0 Tesla (-12.61 +/- 0.97 s(-1)) was greater than observed at 1.5 T (-6.07 +/- 1.38 s(-1), P < 0.05). Cortical R2* levels remained low after furosemide and did not vary with field strength. Correlations between measurements of defined cortical and medullary regions of interest within kidneys were greater at each sampling level and segment at 3.0 T as compared to 1.5 T. For patients studied with 3.0 T, furosemide administration induced a lesser fall in R2* in poststenotic kidneys at 3.0 T (-10.61 +/- 1.61 s(-1)) versus nonstenotic kidneys (-13.21 +/- 0.72 s(-1), P < 0.05). This difference was not evident in comparisons made at 1.5 T. The magnitude of furosemide-suppressible oxygen consumption at 3.0 T (-43%) corresponded more closely with reported experimental differences observed during direct measurement with tissue electrodes (45%-50%) than changes measured at 1.5 T. These results indicate that blood oxygen level dependent MR measurements at high field strength can better distinguish discrete cortical and inner medullary regions of the kidney and approximate measured differences in oxygen tension. Maneuvers that reduce oxygen consumption related to tubular solute transport allow functional evaluation of the interstitial compartment as a function of tissue oxygenation. Impaired response to alterations in oxygen consumption can be detected at 3 T more effectively than at 1.5 T and may provide real-time tools to examine developing parenchymal injury associated with impaired oxygenation.

Automated kidney detection for 3D ultrasound using scan line searching

NASA Astrophysics Data System (ADS)

Noll, Matthias; Nadolny, Anne; Wesarg, Stefan

2016-04-01

Ultrasound (U/S) is a fast and non-expensive imaging modality that is used for the examination of various anatomical structures, e.g. the kidneys. One important task for automatic organ tracking or computer-aided diagnosis is the identification of the organ region. During this process the exact information about the transducer location and orientation is usually unavailable. This renders the implementation of such automatic methods exceedingly challenging. In this work we like to introduce a new automatic method for the detection of the kidney in 3D U/S images. This novel technique analyses the U/S image data along virtual scan lines. Here, characteristic texture changes when entering and leaving the symmetric tissue regions of the renal cortex are searched for. A subsequent feature accumulation along a second scan direction produces a 2D heat map of renal cortex candidates, from which the kidney location is extracted in two steps. First, the strongest candidate as well as its counterpart are extracted by heat map intensity ranking and renal cortex size analysis. This process exploits the heat map gap caused by the renal pelvis region. Substituting the renal pelvis detection with this combined cortex tissue feature increases the detection robustness. In contrast to model based methods that generate characteristic pattern matches, our method is simpler and therefore faster. An evaluation performed on 61 3D U/S data sets showed, that in 55 cases showing none or minor shadowing the kidney location could be correctly identified.

High-resolution mechanical imaging of the kidney.

PubMed

Streitberger, Kaspar-Josche; Guo, Jing; Tzschätzsch, Heiko; Hirsch, Sebastian; Fischer, Thomas; Braun, Jürgen; Sack, Ingolf

2014-02-07

The objective of this study was to test the feasibility and reproducibility of in vivo high-resolution mechanical imaging of the asymptomatic human kidney. Hereby nine volunteers were examined at three different physiological states of urinary bladder filling (a normal state, urinary urgency, and immediately after urinary relief). Mechanical imaging was performed of the in vivo kidney using three-dimensional multifrequency magnetic resonance elastography combined with multifrequency dual elastovisco inversion. Other than in classical elastography, where the storage and loss shear moduli are evaluated, we analyzed the magnitude |G(⁎)| and the phase angle φ of the complex shear modulus reconstructed by simultaneous inversion of full wave field data corresponding to 7 harmonic drive frequencies from 30 to 60Hz and a resolution of 2.5mm cubic voxel size. Mechanical parameter maps were derived with a spatial resolution superior to that in previous work. The group-averaged values of |G(⁎)| were 2.67±0.52kPa in the renal medulla, 1.64±0.17kPa in the cortex, and 1.17±0.21kPa in the hilus. The phase angle φ (in radians) was 0.89±0.12 in the medulla, 0.83±0.09 in the cortex, and 0.72±0.06 in the hilus. All regional differences were significant (P<0.001), while no significant variation was found in relation to different stages of bladder filling. In summary our study provides first high-resolution maps of viscoelastic parameters of the three anatomical regions of the kidney. |G(⁎)| and φ provide novel information on the viscoelastic properties of the kidney, which is potentially useful for the detection of renal lesions or fibrosis. © 2013 Published by Elsevier Ltd.

Evaluation of renal quantitative T2* changes on MRI following administration of ferumoxytol as a T2* contrast agent.

PubMed

Hedgire, Sandeep S; McDermott, Shaunagh; Wojtkiewicz, Gregory R; Abtahi, Seyed Mahdi; Harisinghani, Mukesh; Gaglia, Jason L

2014-01-01

To evaluate the time-dependent changes in regional quantitative T2* maps of the kidney following intravenous administration of ferumoxytol. Twenty-four individuals with normal kidney function underwent T2*-weighted MRI of the kidney before, immediately after, and 48 hours after intravenous administration of ferumoxytol at a dose of 4 mg/kg (group A, n=12) or 6 mg/kg (group B, n=12). T2* values were statistically analyzed using two-tailed paired t-tests. In group A, the percentage changes from baseline to immediate post and baseline to 48 hours were 85.3% and 64.2% for the cortex and 90.8% and 64.6% for the medulla, respectively. In group B, the percentage changes from baseline to immediate post and baseline to 48 hours were 85.2% and 73.4% for the cortex and 94.5% and 74% for the medulla, respectively. This difference was significant for both groups (P<0.0001). There is significant and differential uptake of ferumoxytol in the cortex and medulla of physiologically normal kidneys. This differential uptake may offer the ability to interrogate renal cortex and medulla with possible clinical applications in medical renal disease and transplant organ assessment. We propose an organ of interest based dose titration of ferumoxytol to better differentiate circulating from intracellular ferumoxytol particles.

Kidney Biopsy Adequacy: A Metric-based Study.

PubMed

Ferrer, German; Andeen, Nicole K; Lockridge, Joseph; Norman, Douglas; Foster, Bryan R; Houghton, Donald C; Troxell, Megan L

2018-06-05

There are differences in renal biopsy yield related to on-site evaluation, tissue division, and operator, among others. To understand these variations, we collected adequacy-associated data (%cortex, glomeruli, arteries, length) from consecutive native and allograft kidney biopsies over a 22-month period. In total, 1332 biopsies (native: 873, allograft: 459) were included, 617 obtained by nephrologists, 663 by radiologists, and 559 with access to on-site division. Proceduralists with access to on-site evaluation had significantly lower inadequacy rates and better division of tissue for light microscopy (LM), immunofluorescence, and electron microscopy than those without access to on-site evaluation. Radiologists in our region were significantly less likely to have access to on-site evaluation than nephrologists. On multivariate analysis for native kidney biopsies, the effect of having a radiologist perform the biopsy and having access to on-site division were both significant predictors of obtaining greater calculated amount of cortex for LM. Despite the trend for radiologists to obtain more tissue in general, biopsies from nephrologists contained a greater percentage of cortex and were more likely to be considered adequate for LM (native kidney inadequacy rate for LM: 1.11% vs. 5.41%, P=0.0086). Biopsies in which inadequate or marginal cortical tissue was submitted for LM had only minor decreases in the amount of cortex submitted for immunofluorescence and electron microscopy, revealing an opportunity for improved specimen triaging when limited tissue is obtained. In conclusion, both on-site evaluation/division and proceduralist significantly affect quantitative kidney biopsy metrics, which in turn affects the pathologist's ability to render an accurate diagnosis with appropriate prognostic information for the patient and treating nephrologist.

Comparison of the morphometric features of the left and right horse kidneys: a stereological approach.

PubMed

Bolat, D; Bahar, S; Tipirdamaz, S; Selcuk, M L

2013-12-01

The aims of this study were to determine the total volume of the horse kidney and volume fractions of its functional subcomponents (cortex, medulla, renal pelvis) using stereological methods and investigate any possible difference in the functional subcomponents of the right and left kidneys that may arise from differences in shape. The study was carried out on the kidneys of 5 horses of different breed and sex. The weight of the kidneys was measured by a digital scale, and kidney volume was calculated by Archimedes' principle. Total kidney volume and volume fractions of subcomponents of the right and left kidneys were estimated by the Cavalieri's principle. The weights of the right and left kidneys were 550 ± 25 g and 585 ± 23 g, respectively. The volumes of the right and left kidneys estimated using the Cavalieri method were 542 ± 46 ml and 581 ± 29 ml. The relative organ weight of the kidneys was calculated as 1:330. The densities of the right and left kidneys were determined to be 1.01 and 1.00, respectively. The mean volume fractions of the cortex, medulla and renal pelvis were determined as 55.6, 42.7 and 1.7 in both kidneys. No statistically significant difference existed between morphometric data pertaining to the right and left kidneys (P > 0.05). To determine precisely whether differences in shape cause any difference in the functional subcomponents of the right and left kidneys requires further investigation of differences in the number of microscopically functional unit of the kidney such as renal glomeruli and nephrons. © 2013 Blackwell Verlag GmbH.

Preliminary feasibility study of a new method of hypothermia in an experimental canine model

PubMed Central

Sert, İbrahim Ünal; Akand, Murat; Kılıç, Özcan; Yavru, Nuri; Bulut, Ersan

2017-01-01

Objective To build up a new microcontroller thermoelectric system to achieve renal hypothermia. Material and methods Renal hypothermia system was tested under in vivo conditions in the kidneys of ten Mongrel dogs. Ambient temperature was evaluated using two different microcontrollers. In order to ensure hypothermia in the renal parenchyma, selection can be made among 4 modules and sensors which detect the temperature of the area. The temperature range of the system was adjusted between −50°C and +50°C. Results When single and double poles of the kidney were cooled, initial mean intraperitoneal temperature values were found 37.7°C for rectum and 36.5°C for renal cortex and medulla. After the temperature of the cooling module was set to 12°C, the module was placed on the poles of the kidney. After fifteen minutes, temperature was 15.4°C in the lower pole of the kidney, 28.1°C in the cortex of the other side and 29.2°C in the intramedullary region. The temperature was found to be 15°C in the vicinity and 26.1°C in the cortex across the module. After the system was stabilized, a very slight change was observed in the temperature. Conclusion Hypothermia system developed ensured desired cooling of the targeted part of the kidney; however, it did not cause a change in the temperature of other parts of the kidney or general body temperature. Thus, it was possible to create a long-term study area for renal parenchymal surgery. PMID:28861307

Preliminary feasibility study of a new method of hypothermia in an experimental canine model.

PubMed

Sert, İbrahim Ünal; Akand, Murat; Kılıç, Özcan; Yavru, Nuri; Bulut, Ersan

2017-09-01

To build up a new microcontroller thermoelectric system to achieve renal hypothermia. Renal hypothermia system was tested under in vivo conditions in the kidneys of ten Mongrel dogs. Ambient temperature was evaluated using two different microcontrollers. In order to ensure hypothermia in the renal parenchyma, selection can be made among 4 modules and sensors which detect the temperature of the area. The temperature range of the system was adjusted between -50°C and +50°C. When single and double poles of the kidney were cooled, initial mean intraperitoneal temperature values were found 37.7°C for rectum and 36.5°C for renal cortex and medulla. After the temperature of the cooling module was set to 12°C, the module was placed on the poles of the kidney. After fifteen minutes, temperature was 15.4°C in the lower pole of the kidney, 28.1°C in the cortex of the other side and 29.2°C in the intramedullary region. The temperature was found to be 15°C in the vicinity and 26.1°C in the cortex across the module. After the system was stabilized, a very slight change was observed in the temperature. Hypothermia system developed ensured desired cooling of the targeted part of the kidney; however, it did not cause a change in the temperature of other parts of the kidney or general body temperature. Thus, it was possible to create a long-term study area for renal parenchymal surgery.

Apoptosis of rat kidney cells after 241-americium administration.

PubMed

Labéjof, L; Berry, J P; Duchambon, P; Poncy, J L; Galle, P

1998-01-01

Tumors induction by americium is well known but there are no data on the biological effects of this radionucleide at subcellular level. In order to study the possible ultrastructural lesions induced by this element, a group of rats were injected with 241-Americium-citrate (9 kBq), once a week for five weeks and sacrificed 7 days after the last injection. We describe the alterations observed in the cortex kidney using cytochemical (TUNEL reaction) and histochemical (PAS staining) methods for light microscopy as well as electron microscopy techniques. Various types of lesions were detected: condensation of nuclear chromatine, fragmentation of the nuclei, swollen mitochondria, disappearance of mitochondrial crests and skrinking of the cytoplasm. This study clearly demonstrated the induction of apoptosis by americium in rat cortex kidney cells.

Effect of metallothionein core promoter region polymorphism on cadmium, zinc and copper levels in autopsy kidney tissues from a Turkish population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kayaalti, Zeliha, E-mail: kayaalti@medicine.ankara.edu.t; Mergen, Goerkem; Soeylemezoglu, Tuelin

2010-06-01

Metallothioneins (MTs) are metal-binding, low molecular weight proteins and are involved in pathophysiological processes like metabolism of essential metals, metal ion homeostasis and detoxification of heavy metals. Metallothionein expression is induced by various heavy metals especially cadmium, mercury and zinc; MTs suppress toxicity of heavy metals by binding themselves to these metals. The aim of this study was to investigate the association between the - 5 A/G metallothionein 2A (MT2A) single nucleotide polymorphism (SNP) and Cd, Zn and Cu levels in the renal cortex from autopsy cases. MT2A core promoter region - 5 A/G SNP was analyzed by PCR-RFLP methodmore » using 114 autopsy kidney tissues and the genotype frequencies of this polymorphism were found as 87.7% homozygote typical (AA), 11.4% heterozygote (AG) and 0.9% homozygote atypical (GG). In order to assess the Cd, Zn and Cu levels in the same autopsy kidney tissues, a dual atomic absorption spectrophotometer system was used and the average levels of Cd, Zn and Cu were measured as 95.54 {+-} 65.58 {mu}g/g, 181.20 {+-} 87.72 {mu}g/g and 17.14 {+-} 16.28 {mu}g/g, respectively. As a result, no statistical association was found between the - 5 A/G SNP in the MT2A gene and the Zn and Cu levels in the renal cortex (p > 0.05), but considerably high accumulation of Cd was monitored for individuals having AG (151.24 {+-} 60.21 {mu}g/g) and GG genotypes (153.09 {mu}g/g) compared with individuals having AA genotype (87.72 {+-} 62.98 {mu}g/g) (p < 0.05). These results show that the core promoter region polymorphism of metallothionein 2A increases the accumulation of Cd in human renal cortex.« less

Application of small RNA sequencing to identify microRNAs in acute kidney injury and fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pellegrini, Kathryn L.

Establishing a microRNA (miRNA) expression profile in affected tissues provides an important foundation for the discovery of miRNAs involved in the development or progression of pathologic conditions. We conducted small RNA sequencing to generate a temporal profile of miRNA expression in the kidneys using a mouse model of folic acid-induced (250 mg/kg i.p.) kidney injury and fibrosis. From the 103 miRNAs that were differentially expressed over the time course (> 2-fold, p < 0.05), we chose to further investigate miR-18a-5p, which is expressed during the acute stage of the injury; miR-132-3p, which is upregulated during transition between acute and fibroticmore » injury; and miR-146b-5p, which is highly expressed at the peak of fibrosis. Using qRT-PCR, we confirmed the increased expression of these candidate miRNAs in the folic acid model as well as in other established mouse models of acute injury (ischemia/reperfusion injury) and fibrosis (unilateral ureteral obstruction). In situ hybridization confirmed high expression of miR-18a-5p, miR-132-3p and miR-146b-5p throughout the kidney cortex in mice and humans with severe kidney injury or fibrosis. When primary human proximal tubular epithelial cells were treated with model nephrotoxicants such as cadmium chloride (CdCl{sub 2}), arsenic trioxide, aristolochic acid (AA), potassium dichromate (K{sub 2}Cr{sub 2}O{sub 7}) and cisplatin, miRNA-132-3p was upregulated 4.3-fold after AA treatment and 1.5-fold after K{sub 2}Cr{sub 2}O{sub 7} and CdCl{sub 2} treatment. These results demonstrate the application of temporal small RNA sequencing to identify miR-18a, miR-132 and miR-146b as differentially expressed miRNAs during distinct phases of kidney injury and fibrosis progression. - Highlights: • We used small RNA sequencing to identify differentially expressed miRNAs in kidney. • Distinct patterns were found for acute injury and fibrotic stages in the kidney. • Upregulation of miR-18a, -132 and -146b was confirmed in mice and human kidneys.« less

Arterial spin labeling blood flow magnetic resonance imaging for evaluation of renal injury.

PubMed

Liu, Yupin P; Song, Rui; Liang, Chang hong; Chen, Xin; Liu, Bo

2012-08-15

A multitude of evidence suggests that iodinated contrast material causes nephrotoxicity; however, there have been no previous studies that use arterial spin labeling (ASL) blood flow functional magnetic resonance imaging (fMRI) to investigate the alterations in effective renal plasma flow between normointensive and hypertensive rats following injection of contrast media. We hypothesized that FAIR-SSFSE arterial spin labeling MRI may enable noninvasive and quantitative assessment of regional renal blood flow abnormalities and correlate with disease severity as assessed by histological methods. Renal blood flow (RBF) values of the cortex and medulla of rat kidneys were obtained from ASL images postprocessed at ADW4.3 workstation 0.3, 24, 48, and 72 h before and after injection of iodinated contrast media (6 ml/kg). The H&E method for morphometric measurements was used to confirm the MRI findings. The RBF values of the outer medulla were lower than those of the cortex and the inner medulla as reported previously. Iodinated contrast media treatment resulted in decreases in RBF in the outer medulla and cortex in spontaneously hypertensive rats (SHR), but only in the outer medulla in normotensive rats. The iodinated contrast agent significantly decreased the RBF value in the outer medulla and the cortex in SHR compared with normotensive rats after injection of the iodinated contrast media. Histological observations of kidney morphology were also consistent with ASL perfusion changes. These results demonstrate that the RBF value can reflect changes of renal perfusion in the cortex and medulla. ASL-MRI is a feasible and accurate method for evaluating nephrotoxic drugs-induced kidney damage.

Application of Hanging Drop Technique for Kidney Tissue Culture.

PubMed

Wang, Shaohui; Wang, Ximing; Boone, Jasmine; Wie, Jin; Yip, Kay-Pong; Zhang, Jie; Wang, Lei; Liu, Ruisheng

2017-01-01

The hanging drop technique is a well-established method used in culture of animal tissues. However, this method has not been used in adult kidney tissue culture yet. This study was to explore the feasibility of using this technique for culturing adult kidney cortex to study the time course of RNA viability in the tubules and vasculature, as well as the tissue structural integrity. In each Petri dish with the plate covered with sterile buffer, a section of mouse renal cortex was cultured within a drop of DMEM culture medium on the inner surface of the lip facing downward. The tissue were then harvested at each specific time points for Real-time PCR analysis and histological studies. The results showed that the mRNA level of most Na+ related transporters and cotransporters were stably maintained within 6 hours in culture, and that the mRNA level of most receptors found in the vasculature and glomeruli were stably maintained for up to 9 days in culture. Paraffin sections of the cultured renal cortex indicated that the tubules began to lose tubular integrity after 6 hours, but the glomeruli and vasculatures were still recognizable up to 9 days in culture. We concluded that adult kidney tissue culture by hanging drop method can be used to study gene expressions in vasculature and glomeruli. © 2017 The Author(s). Published by S. Karger AG, Basel.

Abundance of Drug Transporters in the Human Kidney Cortex as Quantified by Quantitative Targeted Proteomics

PubMed Central

Prasad, Bhagwat; Johnson, Katherine; Billington, Sarah; Lee, Caroline; Chung, Git W.; Brown, Colin D.A.; Kelly, Edward J.; Himmelfarb, Jonathan

2016-01-01

Protein expression of renal uptake and efflux transporters was quantified by quantitative targeted proteomics using the surrogate peptide approach. Renal uptake transporters assessed in this study included organic anion transporters (OAT1–OAT4), organic cation transporter 2 (OCT2), organic/carnitine cation transporters (OCTN1 and OCTN2), and sodium-glucose transporter 2 (SGLT2); efflux transporters included P-glycoprotein, breast cancer resistance protein, multidrug resistance proteins (MRP2 and MRP4), and multidrug and toxin extrusion proteins (MATE1 and MATE2-K). Total membrane was isolated from the cortex of human kidneys (N = 41). The isolated membranes were digested by trypsin and the digest was subjected to liquid chromatography–tandem mass spectrometry analysis. The mean expression of surrogate peptides was as follows (given with the standard deviation, in picomoles per milligram of total membrane protein): OAT1 (5.3 ± 1.9), OAT2 (0.9 ± 0.3), OAT3 (3.5 ± 1.6), OAT4 (0.5 ± 0.2), OCT2 (7.4 ± 2.8), OCTN1 (1.3 ± 0.6), OCTN2 (0.6 ± 0.2), P-glycoprotein (2.1 ± 0.8), MRP2 (1.4 ± 0.6), MRP4 (0.9 ± 0.6), MATE1 (5.1 ± 2.3), and SGLT2 (3.7 ± 1.8). Breast cancer resistance protein (BCRP) and MATE2-K proteins were detectable but were below the lower limit of quantification. Interestingly, the protein expression of OAT1 and OAT3 was significantly correlated (r > 0.8). A significant correlation was also observed between expression of multiple other drug transporters, such as OATs/OCT2 or OCTN1/OCTN2, and SGLT2/OCTNs, OCT, OATs, and MRP2. These renal transporter data should be useful in deriving in vitro to in vivo scaling factors to accurately predict renal clearance and kidney epithelial cell exposure to drugs or their metabolites. PMID:27621205

The Utility of the Remnant Kidney Volume/Body Surface Area Ratio and Tumor Diameter as Predictors of Postoperative Degree of Renal Functional Decline in Patients With Renal Cell Carcinoma Treated by Radical Nephrectomy.

PubMed

Sejima, Takehiro; Yamaguchi, Noriya; Iwamoto, Hideto; Masago, Toshihiko; Morizane, Shuichi; Ono, Koji; Koumi, Tsutomu; Honda, Masashi; Takenaka, Atsushi

2015-08-01

To characterize the preoperative factors affecting renal cell carcinoma patients as predictive of post-radical nephrectomy (RN) mild (M-decline) or severe (S-decline) renal functional decline and to elucidate the histopathologic features of the resected normal kidney cortex, as well as the occurrence of cardiovascular disease (CVD) in both M-decline and S-decline patients. M-decline and S-decline were categorized as a percentage of postoperative estimated glomerular filtration rate decline of <20 and of >40, respectively. The preoperative factors analyzed were patient demographics, comorbidities, and radiographic findings, including remnant kidney status and tumor size. The factors based on postoperative information analyzed were tumor and normal cortex pathology and CVD events. In 175 patient cohort, 21 and 32 cases were categorized as M-decline and S-decline, respectively. Absence of comorbidities, larger remnant kidney volume (RKV)/body surface area (BSA) ratio, and larger tumor diameter were significantly predictive of M-decline, whereas smaller tumor diameter was significantly predictive of S-decline. The global glomerulosclerosis extent in nephrectomized normal cortex of S-decline cases was significantly higher than in other types of cases. No CVD event was observed in M-decline cases. This is the first report to identify the RKV/BSA ratio as a promising predictor of post-RN degree of renal functional decline. Post-RN prevention of life-threatening outcomes according to preoperative and postoperative information, including the degree of post-RN renal functional decline and histopathology of the nephrectomized normal cortex, should be considerable in future urological tasks. Copyright © 2015 Elsevier Inc. All rights reserved.

Peptide-induced prostaglandin biosynthesis in the renal-vein-constricted kidney

PubMed Central

Myers, Stuart I.; Zipser, Robert; Needleman, Philip

1981-01-01

The ipsilateral kidney was removed from a rabbit 48h after unilateral partial renal-vein-constriction and was perfused with Krebs–Henseleit media at 37°C. Hourly administration of a fixed dose of bradykinin to the renal-vein-constricted kidney demonstrated a marked time-dependent increase in the release of bioassayable prostaglandin E2 and thromboxane A2 into the venous effluent as compared with the response of the contralateral control kidney. The renal-vein-constricted kidney produced up to 60 times more prostaglandin E2 in response to bradykinin after 6h of perfusion as compared with the contralateral kidney; thromboxane A2 was not demonstratable in the contralateral kidney. Inhibition of protein synthesis de novo in the perfused renal-vein-constricted kidney with cycloheximide lessened the hormone-stimulated increase in prostaglandin E2 by 94% and in thromboxane A2 by 90% at 6h of perfusion. Covalent acetylation of the renal cyclo-oxygenase by prior oral administration of aspirin to the rabbit inhibited initial bradykinin-stimulated prostaglandin E2 biosynthesis 71% at 1h of perfusion. However, there was total recovery from aspirin in the renal-vein-constricted kidney by 2h of perfusion after bradykinin stimulation. Total cyclo-oxygenase activity as measured by [14C]arachidonate metabolism to labelled prostaglandins by renal cortical and renal medullary microsomal fractions prepared from 6h-perfused kidneys demonstrated that renal-vein-constricted kidney-cortical cyclo-oxygenase activity was significantly greater than the contralateral-kidney-cortical conversion, whereas medullary arachidonate metabolism was comparable in both the renal-vein-constricted kidney and contralateral kidney. These data suggest that perfusion of a renal-vein-constricted kidney initiates a time-dependent induction of synthesis of prostaglandin-producing enzymes, which appear to be primarily localized in the renal cortex. The presence of the synthetic capacity to generate very potent vasodilator and vasoconstrictor prostaglandins in the renal cortex suggests that these substances could mediate or modulate changes in renal vascular resistance in pathological states. PMID:6798974

The regulation of growth and metabolism of kidney stem cells with regional specificity using extracellular matrix derived from kidney.

PubMed

O'Neill, John D; Freytes, Donald O; Anandappa, Annabelle J; Oliver, Juan A; Vunjak-Novakovic, Gordana V

2013-12-01

Native extracellular matrix (ECM) that is secreted and maintained by resident cells is of great interest for cell culture and cell delivery. We hypothesized that specialized bioengineered niches for stem cells can be established using ECM-derived scaffolding materials. Kidney was selected as a model system because of the high regional diversification of renal tissue matrix. By preparing the ECM from three specialized regions of the kidney (cortex, medulla, and papilla; whole kidney, heart, and bladder as controls) in three forms: (i) intact sheets of decellularized ECM, (ii) ECM hydrogels, and (iii) solubilized ECM, we investigated how the structure and composition of ECM affect the function of kidney stem cells (with mesenchymal stem cells, MSCs, as controls). All three forms of the ECM regulated KSC function, with differential structural and compositional effects. KSCs cultured on papilla ECM consistently displayed lower proliferation, higher metabolic activity, and differences in cell morphology, alignment, and structure formation as compared to KSCs on cortex and medulla ECM, effects not observed in corresponding MSC cultures. These data suggest that tissue- and region-specific ECM can provide an effective substrate for in vitro studies of therapeutic stem cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human podocyte depletion in association with older age and hypertension.

PubMed

Puelles, Victor G; Cullen-McEwen, Luise A; Taylor, Georgina E; Li, Jinhua; Hughson, Michael D; Kerr, Peter G; Hoy, Wendy E; Bertram, John F

2016-04-01

Podocyte depletion plays a major role in the development and progression of glomerulosclerosis. Many kidney diseases are more common in older age and often coexist with hypertension. We hypothesized that podocyte depletion develops in association with older age and is exacerbated by hypertension. Kidneys from 19 adult Caucasian American males without overt renal disease were collected at autopsy in Mississippi. Demographic data were obtained from medical and autopsy records. Subjects were categorized by age and hypertension as potential independent and additive contributors to podocyte depletion. Design-based stereology was used to estimate individual glomerular volume and total podocyte number per glomerulus, which allowed the calculation of podocyte density (number per volume). Podocyte depletion was defined as a reduction in podocyte number (absolute depletion) or podocyte density (relative depletion). The cortical location of glomeruli (outer or inner cortex) and presence of parietal podocytes were also recorded. Older age was an independent contributor to both absolute and relative podocyte depletion, featuring glomerular hypertrophy, podocyte loss, and thus reduced podocyte density. Hypertension was an independent contributor to relative podocyte depletion by exacerbating glomerular hypertrophy, mostly in glomeruli from the inner cortex. However, hypertension was not associated with podocyte loss. Absolute and relative podocyte depletion were exacerbated by the combination of older age and hypertension. The proportion of glomeruli with parietal podocytes increased with age but not with hypertension alone. These findings demonstrate that older age and hypertension are independent and additive contributors to podocyte depletion in white American men without kidney disease. Copyright © 2016 the American Physiological Society.

Expression of cytochrome P-450 4 enzymes in the kidney and liver: regulation by PPAR and species-difference between rat and human.

PubMed

Ito, Osamu; Nakamura, Yasuhiro; Tan, Liping; Ishizuka, Tsuneo; Sasaki, Yuko; Minami, Naoyoshi; Kanazawa, Masayuki; Ito, Sadayoshi; Sasano, Hironobu; Kohzuki, Masahiro

2006-03-01

Members of the cytochrome P-450 4 (CYP4) family catalyze the omega-hydroxylation of fatty acids, and some of them have the PPAR response element in the promoter area of the genes. The localization of CYP4A and PPAR isoforms and the effect of PPAR agonists on CYP4A protein level and activity were determined in rat kidney and liver. Immunoblot analysis showed that CYP4A was expressed in the liver and proximal tubule, with lower expression in the preglomerular microvessel, glomerulus and thick ascending limb (TAL), but the expression was not detected in the collecting duct. PPARalpha was expressed in the liver, proximal tubule and TAL. PPARgamma was expressed in the collecting duct, with lower expression in the TAL, but no expression in the proximal tubule and liver. The PPARalpha agonist clofibrate induced CYP4A protein levels and activity in the renal cortex and liver. The PPARgamma agonist pioglitazone did not modulate them in these tissues. The localization of CYP4A and CYP4F were further determined in human kidney and liver by immunohistochemical technique. Immunostainings for CYP4A and CYP4F were observed in the hepatocytes of the liver lobule and the proximal tubules, with lower stainings in the TALs and collecting ducts, but no staining in the glomeruli or renal vasculatures. These results indicate that the inducibility of CYP4A by PPAR agonists in the rat tissues correlates with the expression of the respective PPAR isoforms, and that the localization of CYP4 in the kidney has a species-difference between rat and human.

Ion transport and oxygen consumption in kidney cortex slices from young and old rats.

PubMed

Proverbio, F; Proverbio, T; Marín, R

1985-01-01

The effects of aging on active Na+ extrusion and oxygen consumption associated with it were studied in rat kidney cortex cells. It was found that (a) the active extrusion of Na+ undergoing Na/K exchange and the active extrusion of Na+ with Cl- and water were diminished in old rats (24 months) as compared with young rats (3 months); (b) the oxygen consumption associated with each of the two active mechanisms of Na+ extrusion was also diminished in the old rats; (c) the calculated turnover rate of the Na/K pump was significantly lower for the old rats.

Lgr5(+ve) stem/progenitor cells contribute to nephron formation during kidney development.

PubMed

Barker, Nick; Rookmaaker, Maarten B; Kujala, Pekka; Ng, Annie; Leushacke, Marc; Snippert, Hugo; van de Wetering, Marc; Tan, Shawna; Van Es, Johan H; Huch, Meritxell; Poulsom, Richard; Verhaar, Marianne C; Peters, Peter J; Clevers, Hans

2012-09-27

Multipotent stem cells and their lineage-restricted progeny drive nephron formation within the developing kidney. Here, we document expression of the adult stem cell marker Lgr5 in the developing kidney and assess the stem/progenitor identity of Lgr5(+ve) cells via in vivo lineage tracing. The appearance and localization of Lgr5(+ve) cells coincided with that of the S-shaped body around embryonic day 14. Lgr5 expression remained restricted to cell clusters within developing nephrons in the cortex until postnatal day 7, when expression was permanently silenced. In vivo lineage tracing identified Lgr5 as a marker of a stem/progenitor population within nascent nephrons dedicated to generating the thick ascending limb of Henle's loop and distal convoluted tubule. The Lgr5 surface marker and experimental models described here will be invaluable for deciphering the contribution of early nephron stem cells to developmental defects and for isolating human nephron progenitors as a prerequisite to evaluating their therapeutic potential. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

Stanniocalcin 1 effects on the renal gluconeogenesis pathway in rat and fish.

PubMed

Schein, Vanessa; Kucharski, Luiz C; Guerreiro, Pedro M G; Martins, Tiago Leal; Morgado, Isabel; Power, Deborah M; Canario, Adelino V M; da Silva, Roselis S M

2015-10-15

The mammalian kidney contributes significantly to glucose homeostasis through gluconeogenesis. Considering that stanniocalcin 1 (STC1) regulates ATP production, is synthesized and acts in different cell types of the nephron, the present study hypothesized that STC1 may be implicated in the regulation of gluconeogenesis in the vertebrate kidney. Human STC1 strongly reduced gluconeogenesis from (14)C-glutamine in rat renal medulla (MD) slices but not in renal cortex (CX), nor from (14)C-lactic acid. Total PEPCK activity was markedly reduced by hSTC1 in MD but not in CX. Pck2 (mitochondrial PEPCK isoform) was down-regulated by hSTC1 in MD but not in CX. In fish (Dicentrarchus labrax) kidney slices, both STC1-A and -B isoforms decreased gluconeogenesis from (14)C-acid lactic, while STC1-A increased gluconeogenesis from (14)C-glutamine. Overall, our results demonstrate a role for STC1 in the control of glucose synthesis via renal gluconeogenesis in mammals and suggest that it may have a similar role in teleost fishes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Six Month Oral Toxicity Study of WR238605 Succinate in Rats. Volume 2

DTIC Science & Technology

1996-02-02

chronic, per {vascular Accumulation, foamy macrophage KIDNEY Mineralization Inf laomat ion, chronic Nephropathy Hydronephrosis Pyelonephritis...KIDNEY # EX Mineralization Inflammation, chronic Nephropathy Hydronephrosis Py»lonaphrItIs Hyperplasia, pelvic epithelium Pigmentation, cortex...Mineralization Inf Lajaaat ion, chronic Nephropathy Hydronephrosis Pigmentation, cor ten (1) - - - ɚ> (1) - ə> - (1) - ə> - 2L

Induction, immunochemical identity and immunofluorescence localization of an 80 000-molecular-weight peroxisome-proliferation-associated polypeptide (polypeptide PPA-80) and peroxisomal enoyl-CoA hydratase of mouse liver and renal cortex.

PubMed

Lalwani, N D; Reddy, M K; Mangkornkanok-Mark, M; Reddy, J K

1981-07-15

The hypolipidaemic drugs methyl clofenapate, BR-931, Wy-14643 and procetofen induced a marked proliferation of peroxisomes in the parenchymal cells of liver and the proximal-convoluted-tubular epithelium of mouse kidney. The proliferation of peroxisomes was associated with 6-12-fold increase in the peroxisomal palmitoyl-CoA oxidizing capacity of the mouse liver. Enhanced activity of the peroxisomal palmitoyl-CoA oxidation system was also found in the renal-cortical homogenates of hypolipidaemic-drug-treated mice. The activity of enoyl-CoA hydratase in the mouse liver increased 30-50-fold and in the kidney cortex 3-5-fold with hypolipidaemic-drug-induced peroxisome proliferation in these tissues, and over 95% of this induced activity was found to be heat-labile peroxisomal enzyme in both organs. Sodium dodecyl sulphate/polyacrylamide-gel-electrophoretic analysis of large-particle and microsomal fractions obtained from the liver and kidney cortex of mice treated with hypolipidaemic peroxisome proliferators demonstrated a substantial increase in the quantity of an 80000-mol.wt. peroxisome-proliferation-associated polypeptide (polypeptide PPA-80). The heat-labile peroxisomal enoyl-CoA hydratase was purified from the livers of mice treated with the hypolipidaemic drug methyl clofenapate; the antibodies raised against this electrophoretically homogeneous protein yielded a single immunoprecipitin band with purified mouse liver enoyl-CoA hydratase and with liver and kidney cortical extracts of normal and hypolipidaemic-drug-treated mice. These anti-(mouse liver enoyl-CoA hydratase) antibodies also cross-reacted with purified rat liver enoyl-CoA hydratase and with the polypeptide PPA-80 obtained from rat and mouse liver. Immunofluorescence studies with anti-(polypeptide PPA-80) and anti-(peroxisomal enoyl-CoA hydratase) provided visual evidence for the localization and induction of polypeptide PPA-80 and peroxisomal enoyl-CoA hydratase in the liver and kidney respectively of normal and hypolipidaemic-drug-treated mice. In the kidney, the distribution of these two proteins is identical and limited exclusively to the cytoplasm of proximal-convoluted-tubular epithelium. The immunofluorescence studies clearly complement the biochemical and ultrastructural observations of peroxisome induction in the liver and kidney cortex of mice fed on hypolipidaemic drugs. In addition, preliminary ultrastructural studies with the protein-A-gold-complex technique demonstrate that the heat-labile hepatic enoyl-CoA hydratase is localized in the peroxisome matrix.

High-resolution diffusion tensor imaging of the human kidneys using a free-breathing, multi-slice, targeted field of view approach

PubMed Central

Chan, Rachel W; Von Deuster, Constantin; Stoeck, Christian T; Harmer, Jack; Punwani, Shonit; Ramachandran, Navin; Kozerke, Sebastian; Atkinson, David

2014-01-01

Fractional anisotropy (FA) obtained by diffusion tensor imaging (DTI) can be used to image the kidneys without any contrast media. FA of the medulla has been shown to correlate with kidney function. It is expected that higher spatial resolution would improve the depiction of small structures within the kidney. However, the achievement of high spatial resolution in renal DTI remains challenging as a result of respiratory motion and susceptibility to diffusion imaging artefacts. In this study, a targeted field of view (TFOV) method was used to obtain high-resolution FA maps and colour-coded diffusion tensor orientations, together with measures of the medullary and cortical FA, in 12 healthy subjects. Subjects were scanned with two implementations (dual and single kidney) of a TFOV DTI method. DTI scans were performed during free breathing with a navigator-triggered sequence. Results showed high consistency in the greyscale FA, colour-coded FA and diffusion tensors across subjects and between dual- and single-kidney scans, which have in-plane voxel sizes of 2 × 2 mm2 and 1.2 × 1.2 mm2, respectively. The ability to acquire multiple contiguous slices allowed the medulla and cortical FA to be quantified over the entire kidney volume. The mean medulla and cortical FA values were 0.38 ± 0.017 and 0.21 ± 0.019, respectively, for the dual-kidney scan, and 0.35 ± 0.032 and 0.20 ± 0.014, respectively, for the single-kidney scan. The mean FA between the medulla and cortex was significantly different (p < 0.001) for both dual- and single-kidney implementations. High-spatial-resolution DTI shows promise for improving the characterization and non-invasive assessment of kidney function. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd. PMID:25219683

High-resolution diffusion tensor imaging of the human kidneys using a free-breathing, multi-slice, targeted field of view approach.

PubMed

Chan, Rachel W; Von Deuster, Constantin; Stoeck, Christian T; Harmer, Jack; Punwani, Shonit; Ramachandran, Navin; Kozerke, Sebastian; Atkinson, David

2014-11-01

Fractional anisotropy (FA) obtained by diffusion tensor imaging (DTI) can be used to image the kidneys without any contrast media. FA of the medulla has been shown to correlate with kidney function. It is expected that higher spatial resolution would improve the depiction of small structures within the kidney. However, the achievement of high spatial resolution in renal DTI remains challenging as a result of respiratory motion and susceptibility to diffusion imaging artefacts. In this study, a targeted field of view (TFOV) method was used to obtain high-resolution FA maps and colour-coded diffusion tensor orientations, together with measures of the medullary and cortical FA, in 12 healthy subjects. Subjects were scanned with two implementations (dual and single kidney) of a TFOV DTI method. DTI scans were performed during free breathing with a navigator-triggered sequence. Results showed high consistency in the greyscale FA, colour-coded FA and diffusion tensors across subjects and between dual- and single-kidney scans, which have in-plane voxel sizes of 2 × 2 mm(2) and 1.2 × 1.2 mm(2) , respectively. The ability to acquire multiple contiguous slices allowed the medulla and cortical FA to be quantified over the entire kidney volume. The mean medulla and cortical FA values were 0.38 ± 0.017 and 0.21 ± 0.019, respectively, for the dual-kidney scan, and 0.35 ± 0.032 and 0.20 ± 0.014, respectively, for the single-kidney scan. The mean FA between the medulla and cortex was significantly different (p < 0.001) for both dual- and single-kidney implementations. High-spatial-resolution DTI shows promise for improving the characterization and non-invasive assessment of kidney function. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.

Changes in metabolic profiles during acute kidney injury and recovery following ischemia/reperfusion.

PubMed

Wei, Qingqing; Xiao, Xiao; Fogle, Paul; Dong, Zheng

2014-01-01

Changes of metabolism have been implicated in renal ischemia/reperfusion injury (IRI). However, a global analysis of the metabolic changes in renal IRI is lacking and the association of the changes with ischemic kidney injury and subsequent recovery are unclear. In this study, mice were subjected to 25 minutes of bilateral renal IRI followed by 2 hours to 7 days of reperfusion. Kidney injury and subsequent recovery was verified by serum creatinine and blood urea nitrogen measurements. The metabolome of plasma, kidney cortex, and medulla were profiled by the newly developed global metabolomics analysis. Renal IRI induced overall changes of the metabolome in plasma and kidney tissues. The changes started in renal cortex, followed by medulla and plasma. In addition, we identified specific metabolites that may contribute to early renal injury response, perturbed energy metabolism, impaired purine metabolism, impacted osmotic regulation and the induction of inflammation. Some metabolites, such as 3-indoxyl sulfate, were induced at the earliest time point of renal IRI, suggesting the potential of being used as diagnostic biomarkers. There was a notable switch of energy source from glucose to lipids, implicating the importance of appropriate nutrition supply during treatment. In addition, we detected the depressed polyols for osmotic regulation which may contribute to the loss of kidney function. Several pathways involved in inflammation regulation were also induced. Finally, there was a late induction of prostaglandins, suggesting their possible involvement in kidney recovery. In conclusion, this study demonstrates significant changes of metabolome kidney tissues and plasma in renal IRI. The changes in specific metabolites are associated with and may contribute to early injury, shift of energy source, inflammation, and late phase kidney recovery.

Changes in Metabolic Profiles during Acute Kidney Injury and Recovery following Ischemia/Reperfusion

PubMed Central

Wei, Qingqing; Xiao, Xiao; Fogle, Paul; Dong, Zheng

2014-01-01

Changes of metabolism have been implicated in renal ischemia/reperfusion injury (IRI). However, a global analysis of the metabolic changes in renal IRI is lacking and the association of the changes with ischemic kidney injury and subsequent recovery are unclear. In this study, mice were subjected to 25 minutes of bilateral renal IRI followed by 2 hours to 7 days of reperfusion. Kidney injury and subsequent recovery was verified by serum creatinine and blood urea nitrogen measurements. The metabolome of plasma, kidney cortex, and medulla were profiled by the newly developed global metabolomics analysis. Renal IRI induced overall changes of the metabolome in plasma and kidney tissues. The changes started in renal cortex, followed by medulla and plasma. In addition, we identified specific metabolites that may contribute to early renal injury response, perturbed energy metabolism, impaired purine metabolism, impacted osmotic regulation and the induction of inflammation. Some metabolites, such as 3-indoxyl sulfate, were induced at the earliest time point of renal IRI, suggesting the potential of being used as diagnostic biomarkers. There was a notable switch of energy source from glucose to lipids, implicating the importance of appropriate nutrition supply during treatment. In addition, we detected the depressed polyols for osmotic regulation which may contribute to the loss of kidney function. Several pathways involved in inflammation regulation were also induced. Finally, there was a late induction of prostaglandins, suggesting their possible involvement in kidney recovery. In conclusion, this study demonstrates significant changes of metabolome kidney tissues and plasma in renal IRI. The changes in specific metabolites are associated with and may contribute to early injury, shift of energy source, inflammation, and late phase kidney recovery. PMID:25191961

Quantification of single-kidney glomerular filtration rate with electron-beam computed tomography

NASA Astrophysics Data System (ADS)

Lerman, Lilach O.; Ritman, Erik L.; Pelaez, Laura I.; Sheedy, Patrick F., II; Krier, James D.

2000-04-01

The ability to accurately and noninvasively quantify single- kidney GFR could be invaluable for assessment of renal function. We developed a model that enables this measurement with EBCT. To examine the reliability of this method, EBCT renal flow and volume studies after contrast media administration were performed in pigs with unilateral renal artery stenosis (Group 1), controls (Group 2), and simultaneously with inulin clearance (Group 3). Renal flow curves, obtained from the bilateral renal cortex and medulla, depicted transit of the contrast through the vascular and tubular compartments, and were fitted using extended gamma- variate functions. Renal blood flow was calculated as the sum of products of cortical and medullary perfusions and volumes. Normalized GFR (mL/min/cc) was calculated using the rate (maximal slope) of proximal tubular contrast accumulation, and EBCT-GFR as normalized GFR* cortical volume. In Group 1, the decreased GFR of the stenotic kidney correlated well with its decreased volume and RBF, and with the degree of stenosis (r equals -0.99). In Group 3, EBCT-GFR correlated well with inulin clearance (slope 1.1, r equals 0.81). This novel approach can be very useful for quantification of concurrent regional hemodynamics and function in the intact kidneys, in a manner potentially applicable to humans.

[Intrarenal smooth muscle: histology of a complex urodymamic machine].

PubMed

Arias, L F; Ortiz-Arango, N

2013-03-01

To know better the microscopic arrangement of the bundles of smooth muscle in the human renal parenchyma, their distribution and anatomical relationships, trying to make a reconstruction of this muscular system. Five adult human kidneys and one fetal kidney were processed "in toto" with cross sections every 300μm. In the histological sections we identify the smooth muscle fibers trying to determine its insertion, course and anatomical relationship with other structures of the kidney tissue. There are bundles of smooth muscle fibers of variable thickness parallel to the edges of the medullary pyramids, bundles that surrounding the medulla in a spiral course, and bundles that accompany arcuate vessels, the latter being the most abundant and easy to identify. These groups of muscle fibers do not have a precise or constant insertion site, their periodicity is not homogeneous and they are not a direct extension of the muscle of the renal pelvis, although some bundles are in contact with it. There are also unusual and inconstant small muscle fibers no associated to vessels in the interstitium of the cortex and, exceptionally, in the medulla. There is a complex microscopic system of smooth muscle fibers that partially surround the renal medulla and are related to renal pelvic muscles without a direct continuity with them. Although this small muscular system is under-recognized, could be very important in urodynamics. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

Aged rats are more vulnerable than adolescents to "ecstasy"-induced toxicity.

PubMed

Feio-Azevedo, R; Costa, V M; Barbosa, D J; Teixeira-Gomes, A; Pita, I; Gomes, S; Pereira, F C; Duarte-Araújo, M; Duarte, J A; Marques, F; Fernandes, E; Bastos, M L; Carvalho, F; Capela, J P

2018-06-04

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a widespread drug of abuse with known neurotoxic properties. The present study aimed to evaluate the differential toxic effects of MDMA in adolescent and aged Wistar rats, using doses pharmacologically comparable to humans. Adolescent (post-natal day 40) (3 × 5 mg/kg, 2 h apart) and aged (mean 20 months old) (2 × 5 mg/kg, 2 h apart) rats received MDMA intraperitoneally. Animals were killed 7 days later, and the frontal cortex, hippocampus, striatum and cerebellum brain areas were dissected, and heart, liver and kidneys were collected. MDMA caused hyperthermia in both treated groups, but aged rats had a more dramatic temperature elevation. MDMA promoted serotonergic neurotoxicity only in the hippocampus of aged, but not in the adolescents' brain, and did not change the levels of dopamine or serotonin metabolite in the striatum of both groups. Differential responses according to age were also seen regarding brain p-Tau levels, a hallmark of a degenerative brain, since only aged animals had significant increases. MDMA evoked brain oxidative stress in the hippocampus and striatum of aged, and in the hippocampus, frontal cortex, and striatum brain areas of adolescents according to protein carbonylation, but only decreased GSH levels in the hippocampus of aged animals. The brain maturational stage seems crucial for MDMA-evoked serotonergic neurotoxicity. Aged animals were more susceptible to MDMA-induced tissue damage in the heart and kidneys, and both ages had an increase in liver fibrotic tissue content. In conclusion, age is a determinant factor for the toxic events promoted by "ecstasy". This work demonstrated special susceptibility of aged hippocampus to MDMA neurotoxicity, as well as impressive damage to the heart and kidney tissue following "ecstasy".

Computed Tomography Volumetry in Preoperative Living Kidney Donor Assessment for Prediction of Split Renal Function.

PubMed

Wahba, Roger; Franke, Mareike; Hellmich, Martin; Kleinert, Robert; Cingöz, Tülay; Schmidt, Matthias C; Stippel, Dirk L; Bangard, Christopher

2016-06-01

Transplant centers commonly evaluate split renal function (SRF) with Tc-99m-mercapto-acetyltriglycin (MAG3) scintigraphy in living kidney donation. Alternatively, the kidney volume can be measured based on predonation CT scans. The aim of this study was to identify the most accurate CT volumetry technique for SRF and the prediction of postdonation kidney function (PDKF). Three CT volumetry techniques (modified ellipsoid volume [MELV], smart region of interest [ROI] volume, renal cortex volume [RCV]) were performed in 101 living kidney donors. Preoperation CT volumetric SRF was determined and compared with MAG3-SRF, postoperation donor kidney function, and graft function. The correlation between donors predonation total kidney volume and predonation kidney function was the highest for RCV (0.58 with creatine clearance, 0.54 with estimated glomerular filtration rate-Cockcroft-Gault). The predonation volume of the preserved kidney was (ROI, MELV, RCV) 148.0 ± 29.1 cm, 151.2 ± 35.4 and 93.9 ± 25.2 (P < 0.005 MELV vs RCV and ROI vs RCV). Bland-Altman analysis showed agreement between CT volumetry SRF and MAG3-SRF (bias, 95% limits of agreement: ROI vs MAG3 0.4%, -7.7% to 8.6%; MELV vs MAG3 0.4%, -8.9% to 9.7%; RCV vs MAG3 0.8%, -9.1% to 10.7%). The correlation between predonation CT volumetric SRF of the preserved kidney and PDKF at day 3 was r = 0.85 to 0.88, between MAG3-SRF and PDKF (r = 0.84). The difference of predonation SRF between preserved and donated kidney was the lowest for ROI and RCV (median, 3% and 4%; 95th percentile, 9% and 13%). Overall renal cortex volumetry seems to be the most accurate technique for the evaluation of predonation SRF and allows a reliable prediction of donor's PDKF.

Transcription factor Nrf2 hyperactivation in early-phase renal ischemia-reperfusion injury prevents tubular damage progression.

PubMed

Nezu, Masahiro; Souma, Tomokazu; Yu, Lei; Suzuki, Takafumi; Saigusa, Daisuke; Ito, Sadayoshi; Suzuki, Norio; Yamamoto, Masayuki

2017-02-01

Acute kidney injury is a devastating disease with high morbidity in hospitalized patients and contributes to the pathogenesis of chronic kidney disease. An underlying mechanism of acute kidney injury involves ischemia-reperfusion injury which, in turn, induces oxidative stress and provokes organ damage. Nrf2 is a master transcription factor that regulates the cellular response to oxidative stress. Here, we examined the role of Nrf2 in the progression of ischemia-reperfusion injury-induced kidney damage in mice using genetic and pharmacological approaches. Both global and tubular-specific Nrf2 activation enhanced gene expression of antioxidant and NADPH synthesis enzymes, including glucose-6-phosphate dehydrogenase, and ameliorated both the initiation of injury in the outer medulla and the progression of tubular damage in the cortex. Myeloid-specific Nrf2 activation was ineffective. Short-term administration of the Nrf2 inducer CDDO during the initial phase of injury ameliorated the late phase of tubular damage. This inducer effectively protected the human proximal tubular cell line HK-2 from oxidative stress-mediated cell death while glucose-6-phosphate dehydrogenase knockdown increased intracellular reactive oxygen species. These findings demonstrate that tubular hyperactivation of Nrf2 in the initial phase of injury prevents the progression of reactive oxygen species-mediated tubular damage by inducing antioxidant enzymes and NADPH synthesis. Thus, Nrf2 may be a promising therapeutic target for preventing acute kidney injury to chronic kidney disease transition. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Renal sensory and sympathetic nerves reinnervate the kidney in a similar time-dependent fashion after renal denervation in rats

PubMed Central

Mulder, Jan; Hökfelt, Tomas; Knuepfer, Mark M.

2013-01-01

Efferent renal sympathetic nerves reinnervate the kidney after renal denervation in animals and humans. Therefore, the long-term reduction in arterial pressure following renal denervation in drug-resistant hypertensive patients has been attributed to lack of afferent renal sensory reinnervation. However, afferent sensory reinnervation of any organ, including the kidney, is an understudied question. Therefore, we analyzed the time course of sympathetic and sensory reinnervation at multiple time points (1, 4, and 5 days and 1, 2, 3, 4, 6, 9, and 12 wk) after renal denervation in normal Sprague-Dawley rats. Sympathetic and sensory innervation in the innervated and contralateral denervated kidney was determined as optical density (ImageJ) of the sympathetic and sensory nerves identified by immunohistochemistry using antibodies against markers for sympathetic nerves [neuropeptide Y (NPY) and tyrosine hydroxylase (TH)] and sensory nerves [substance P and calcitonin gene-related peptide (CGRP)]. In denervated kidneys, the optical density of NPY-immunoreactive (ir) fibers in the renal cortex and substance P-ir fibers in the pelvic wall was 6, 39, and 100% and 8, 47, and 100%, respectively, of that in the contralateral innervated kidney at 4 days, 4 wk, and 12 wk after denervation. Linear regression analysis of the optical density of the ratio of the denervated/innervated kidney versus time yielded similar intercept and slope values for NPY-ir, TH-ir, substance P-ir, and CGRP-ir fibers (all R2 > 0.76). In conclusion, in normotensive rats, reinnervation of the renal sensory nerves occurs over the same time course as reinnervation of the renal sympathetic nerves, both being complete at 9 to 12 wk following renal denervation. PMID:23408032

Impact of blood flow on diffusion coefficients of the human kidney: a time-resolved ECG-triggered diffusion-tensor imaging (DTI) study at 3T.

PubMed

Heusch, Philipp; Wittsack, Hans-Jörg; Kröpil, Patric; Blondin, Dirk; Quentin, Michael; Klasen, Janina; Pentang, Gael; Antoch, Gerald; Lanzman, Rotem S

2013-01-01

To evaluate the impact of renal blood flow on apparent diffusion coefficients (ADC) and fractional anisotropy (FA) using time-resolved electrocardiogram (ECG)-triggered diffusion-tensor imaging (DTI) of the human kidneys. DTI was performed in eight healthy volunteers (mean age 29.1 ± 3.2) using a single slice coronal echoplanar imaging (EPI) sequence (3 b-values: 0, 50, and 300 s/mm(2)) at the timepoint of minimum (20 msec after R wave) and maximum renal blood flow (200 msec after R wave) at 3T. Following 2D motion correction, region of interest (ROI)-based analysis of cortical and medullary ADC- and FA-values was performed. ADC-values of the renal cortex at maximum blood flow (2.6 ± 0.19 × 10(-3) mm(2)/s) were significantly higher than at minimum blood flow (2.2 ± 0.11 × 10(-3) mm(2)/s) (P < 0.001), while medullary ADC-values did not differ significantly (maximum blood flow: 2.2 ± 0.18 × 10(-3) mm(2)/s; minimum blood flow: 2.15 ± 0.14 × 10(-3) mm(2)/s). FA-values of the renal medulla were significantly greater at maximal blood (0.53 ± 0.05) than at minimal blood flow (0.47 ± 0.05) (P < 0.01). In contrast, cortical FA-values were comparable at different timepoints of the cardiac cycle. ADC-values in the renal cortex as well as FA-values in the renal medulla are influenced by renal blood flow. This impact has to be considered when interpreting renal ADC- and FA-values. Copyright © 2012 Wiley Periodicals, Inc.

Effect of cisplatin on organic ion transport in membrane vesicles from rat kidney cortex.

PubMed

Williams, P D; Hottendorf, G H

1985-01-01

Purified renal membrane vesicles were utilized to gain indirect information regarding the renal handling of cisplatin. The effects of cisplatin on prototypical organic anion (p-amino-hippurate, PAH) and cation (N1-methylnicotinamide; tetraethylammonium, TEA) transport in brush border and basolateral membrane vesicles prepared from rat kidney cortex were observed. While cisplatin inhibited organic cation transport (N1-methylnicotinamide; TEA) in brush border and basolateral membranes, no interaction with the organic anion (p-amino-hippurate) system was observed. Kinetic analyses revealed that cisplatin is a competitive inhibitor of TEA transport in brush border membranes with a ki of 0.12 mM. While the relationship between organic cation transport inhibition and cisplatin nephrotoxicity is unknown, it may suggest that the cisplatin complex itself is transported into the kidney by the organic cation system. The reported effect of the organic anion, probenecid, on the renal handling of cisplatin is discussed in light of these results.

RADIOGRAPHIC AND ULTRASONOGRAPHIC ABDOMINAL ANATOMY IN CAPTIVE RING-TAILED LEMURS (LEMUR CATTA).

PubMed

Makungu, Modesta; du Plessis, Wencke M; Barrows, Michelle; Groenewald, Hermanus B; Koeppel, Katja N

2016-06-01

The ring-tailed lemur (Lemur catta) is primarily distributed in south and southwestern Madagascar. It is classified as an endangered species by the International Union for Conservation of Nature. Various abdominal diseases, such as hepatic lipidosis, intestinal ulcers, cystitis, urinary tract obstruction, and neoplasia (e.g., colonic adenocarcinoma and cholangiocarcinoma), have been reported in this species. The aim of this study was to describe the normal radiographic and ultrasonographic abdominal anatomy in captive ring-tailed lemurs to provide guidance for clinical use. Radiography of the abdomen and ultrasonography of the liver, spleen, kidneys, and urinary bladder were performed in 13 and 9 healthy captive ring-tailed lemurs, respectively, during their annual health examinations. Normal radiographic and ultrasonographic reference ranges for abdominal organs were established and ratios were calculated. The majority (12/13) of animals had seven lumbar vertebrae. The sacrum had mainly (12/13) three segments. Abdominal serosal detail was excellent in all animals, and hypaxial muscles were conspicuous in the majority (11/13) of animals. The spleen was frequently (12/13) seen on the ventrodorsal (VD) view and rarely (3/13) on the right lateral (RL) view. The liver was less prominent and well contained within the ribcage. The pylorus was mostly (11/13) located to the right of the midline. The right and left kidneys were visible on the RL and VD views, with the right kidney positioned more cranial and dorsal to the left kidney. On ultrasonography, the kidneys appeared ovoid on transverse and longitudinal views. The medulla was hypoechoic to the renal cortex. The renal cortex was frequently (8/9) isoechoic and rarely (1/9) hyperechoic to the splenic parenchyma. The liver parenchyma was hypoechoic (5/5) to the renal cortex. Knowledge of the normal radiographic and ultrasonographic abdominal anatomy of ring-tailed lemurs may be useful in the diagnosis of diseases and in routine health examinations.

Anemia in new congenital adult type polycystic kidney mice.

PubMed

Koumegawa, J; Nagano, N; Arai, H; Wada, M; Kusaka, M; Takahashi, H

1991-12-01

Mechanisms for the development of anemia and the effects of recombinant human erythropoietin (r-HuEPO) on hematological parameters were studied in new congenital adult type polycystic kidney (DBA/2FG-pcy) mice. The majority of DBA/2FG-pcy mice showed progressive anemia and an elevation of blood urea nitrogen, while a minority showed progressive anemia following polycythemia. Kidneys with numerous cysts in the cortex and medulla occupied virtually the entire abdominal cavity, and the combined kidney weight taken as a percentage of body weight reached 13.5% in the DBA/2FG-pcy mouse. The osmotic fragility of DBA/2FG-pcy mice erythrocytes was significantly increased compared with that of normal control mice. In addition, two-fold increases in serum EPO levels, determined by radioimmunoassay, and a decreased number of colony forming unit-erythroid (CFU-E) were observed in the DBA/2FG-pcy mice. The administration of r-HuEPO during anemia significantly increased the red blood cell count, hemoglobin concentration, hematocrit and reticulocyte percentage in a dose-dependent manner. These findings indicate that anemia in the DBA/2FG-pcy mouse is due to increased fragility of erythrocytes, a deficiency in EPO for the degree of anemia and a decreased number or a decreased response of erythroid progenitor cells. We suggest that the DBA/2FG-pcy mouse is a useful spontaneous model of chronic progressive renal failure.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dissanayake, V.U.; Hughes, J.; Hunter, J.C.

The specific binding of the selective {mu}-, {delta}-, and {kappa}-opioid ligands (3H)(D-Ala2,MePhe4,Gly-ol5)enkephalin ((3H) DAGOL), (3H)(D-Pen2,D-Pen5)enkephalin ((3H)DPDPE), and (3H)U69593, respectively, to crude membranes of the guinea pig and rat whole kidney, kidney cortex, and kidney medulla was investigated. In addition, the distribution of specific 3H-opioid binding sites in the guinea pig and rat kidney was visualized by autoradiography. Homogenate binding and autoradiography demonstrated the absence of {mu}- and {kappa}-opioid binding sites in the guinea pig kidney. No opioid binding sites were demonstrable in the rat kidney. In the guinea pig whole kidney, cortex, and medulla, saturation studies demonstrated that (3H)DPDPE boundmore » with high affinity (KD = 2.6-3.5 nM) to an apparently homogeneous population of binding sites (Bmax = 8.4-30 fmol/mg of protein). Competition studies using several opioid compounds confirmed the nature of the {delta}-opioid binding site. Autoradiography experiments demonstrated that specific (3H)DPDPE binding sites were distributed radially in regions of the inner and outer medulla and at the corticomedullary junction of the guinea pig kidney. Computer-assisted image analysis of saturation data yielded KD values (4.5-5.0 nM) that were in good agreement with those obtained from the homogenate binding studies. Further investigation of the {delta}-opioid binding site in medulla homogenates, using agonist ((3H)DPDPE) and antagonist ((3H)diprenorphine) binding in the presence of Na+, Mg2+, and nucleotides, suggested that the {delta}-opioid site is linked to a second messenger system via a GTP-binding protein. Further studies are required to establish the precise localization of the {delta} binding site in the guinea pig kidney and to determine the nature of the second messenger linked to the GTP-binding protein in the medulla.« less

Qualitative and Quantitative Imaging Evaluation of Renal Cell Carcinoma Subtypes with Grating-based X-ray Phase-contrast CT

NASA Astrophysics Data System (ADS)

Braunagel, Margarita; Birnbacher, Lorenz; Willner, Marian; Marschner, Mathias; De Marco, Fabio; Viermetz, Manuel; Notohamiprodjo, Susan; Hellbach, Katharina; Auweter, Sigrid; Link, Vera; Woischke, Christine; Reiser, Maximilian F.; Pfeiffer, Franz; Notohamiprodjo, Mike; Herzen, Julia

2017-03-01

Current clinical imaging methods face limitations in the detection and correct characterization of different subtypes of renal cell carcinoma (RCC), while these are important for therapy and prognosis. The present study evaluates the potential of grating-based X-ray phase-contrast computed tomography (gbPC-CT) for visualization and characterization of human RCC subtypes. The imaging results for 23 ex vivo formalin-fixed human kidney specimens obtained with phase-contrast CT were compared to the results of the absorption-based CT (gbCT), clinical CT and a 3T MRI and validated using histology. Regions of interest were placed on each specimen for quantitative evaluation. Qualitative and quantitative gbPC-CT imaging could significantly discriminate between normal kidney cortex (54 ± 4 HUp) and clear cell (42 ± 10), papillary (43 ± 6) and chromophobe RCCs (39 ± 7), p < 0.05 respectively. The sensitivity for detection of tumor areas was 100%, 50% and 40% for gbPC-CT, gbCT and clinical CT, respectively. RCC architecture like fibrous strands, pseudocapsules, necrosis or hyalinization was depicted clearly in gbPC-CT and was not equally well visualized in gbCT, clinical CT and MRI. The results show that gbPC-CT enables improved discrimination of normal kidney parenchyma and tumorous tissues as well as different soft-tissue components of RCCs without the use of contrast media.

Origin of Parietal Podocytes in Atubular Glomeruli Mapped by Lineage Tracing

PubMed Central

Schulte, Kevin; Berger, Katja; Boor, Peter; Jirak, Peggy; Gelman, Irwin H.; Arkill, Kenton P.; Neal, Christopher R.; Kriz, Wilhelm; Floege, Jürgen; Smeets, Bart

2014-01-01

Parietal podocytes are fully differentiated podocytes lining Bowman’s capsule where normally only parietal epithelial cells (PECs) are found. Parietal podocytes form throughout life and are regularly observed in human biopsies, particularly in atubular glomeruli of diseased kidneys; however, the origin of parietal podocytes is unresolved. To assess the capacity of PECs to transdifferentiate into parietal podocytes, we developed and characterized a novel method for creating atubular glomeruli by electrocoagulation of the renal cortex in mice. Electrocoagulation produced multiple atubular glomeruli containing PECs as well as parietal podocytes that projected from the vascular pole and lined Bowman’s capsule. Notably, induction of cell death was evident in some PECs. In contrast, Bowman’s capsules of control animals and normal glomeruli of electrocoagulated kidneys rarely contained podocytes. PECs and podocytes were traced by inducible and irreversible genetic tagging using triple transgenic mice (PEC- or Pod-rtTA/LC1/R26R). Examination of serial cryosections indicated that visceral podocytes migrated onto Bowman’s capsule via the vascular stalk; direct transdifferentiation from PECs to podocytes was not observed. Similar results were obtained in a unilateral ureter obstruction model and in human diseased kidney biopsies, in which overlap of PEC- or podocyte-specific antibody staining indicative of gradual differentiation did not occur. These results suggest that induction of atubular glomeruli leads to ablation of PECs and subsequent migration of visceral podocytes onto Bowman’s capsule, rather than transdifferentiation from PECs to parietal podocytes. PMID:24071005

Enalapril and captopril enhance glutathione-dependent antioxidant defenses in mouse tissues.

PubMed

de Cavanagh, E M; Inserra, F; Ferder, L; Fraga, C G

2000-03-01

The effect of enalapril and captopril on total glutathione content (GSSG + GSH) and selenium-dependent glutathione peroxidase (Se-GPx) and glutathione reductase (GSSG-Rd) activities was investigated in mouse tissues. CF-1 mice (4-mo-old females) received water containing enalapril (20 mg/l) or captopril (50 mg/l) for 11 wk. Enalapril increased GSSG + GSH content (P < 0.05) in erythrocytes (147%), brain (112%), and lung (67%), and captopril increased GSSG + GSH content in erythrocytes (190%) and brain (132%). Enalapril enhanced Se-GPx activity in kidney cortex (42%) and kidney medulla (23%) and captopril in kidney cortex (30%). GSSG-Rd activity was enhanced by enalapril in erythrocytes (21%), brain (21%), liver (18%), and kidney cortex (53%) and by captopril in erythrocytes (25%), brain (19%), and liver (34%). In vitro erythrocyte oxidant stress was evaluated by thiobarbituric acid-reactive substances (TBARS) production (control 365 +/- 11, enalapril 221 +/- 26, captopril 206 +/- 17 nmol TBARS x g Hb(-1) x h(-1); both P < 0.05 vs. control) and phenylhydrazine-induced methemoglobin (MetHb) formation (control 66.5 +/- 3.5, enalapril 52.9 +/- 0.4, captopril: 56.4 +/- 2.9 micromol MetHb/g Hb; both P < 0.05 vs. control). Both angiotensin-converting enzyme inhibitor treatments were associated with increased nitric oxide production, as assessed by plasma NO-(3) + NO-(2) level determination (control 9.22 +/- 0.64, enalapril 13.7 +/- 1.9, captopril 17.3 +/- 3.0 micromol NO-(3) + NO-(2)/l plasma; both P < 0.05 vs. control). These findings support our previous reports on the enalapril- and captopril-induced enhancement of endogenous antioxidant defenses and include new data on glutathione-dependent defenses, thus furthering current knowledge on the association of ACE inhibition and antioxidants.

Catabolism of 6-ketoprostaglandin F1alpha by the rat kidney cortex.

PubMed

Pace-Asciak, C R; Domazet, Z; Carrara, M

1977-05-25

Homogenates of the rat kidney cortex converted 5,8,9,11,12,14,15-hepta-tritiated 6-ketoprostaglandin F 1alpha into one major product identified by gas chromatography-mass spectrometry of the methoxime-methyl ester trimethylsilyl ether derivative as 6,15-diketo-9,11-dihydroxyprost-13-enoic acid. The sequence of derivatisation i.e. methoximation prior to methylation, was crucial as methylation of 15-keto catabolites of the E, F and 6-keto-F series affords degradation products. The corresponding 15-keto-13,14-dihydro catabolite was formed in much smaller quantities. Time course studies indicated that 6-keto-prostaglandin F1alpha was catabolised at a slower rate (about 2-5 fold) than prostaglandin F1alpha. The catabolic activity was blocked by NADH.

Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney.

PubMed

Cano-Europa, Edgar; Blas-Valdivia, Vanessa; Franco-Colin, Margarita; Gallardo-Casas, Carlos Angel; Ortiz-Butrón, Rocio

2011-01-01

It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole. Copyright © 2009 Elsevier GmbH. All rights reserved.

Biodistribution and pharmacokinetics of recombinant α1-microglobulin and its potential use in radioprotection of kidneys

PubMed Central

Ahlstedt, Jonas; Tran, Thuy A; Strand, Filip; Holmqvist, Bo; Strand, Sven-Erik; Gram, Magnus; Åkerström, Bo

2015-01-01

Peptide-receptor radionuclide therapy (PRRT) is a systemically administrated molecular targeted radiation therapy for treatment of neuroendocrine tumors. Fifteen years of clinical use show that renal toxicity, due to glomerular filtration of the peptides followed by local generation of highly reactive free radicals, is the main side-effect that limits the maximum activity that can be administrated for efficient therapy. α1-microglobulin (A1M) is an endogenous radical scavenger shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. An important feature of A1M is that, following distribution to the blood, it is equilibrated to the extravascular compartments and filtrated in the kidneys. Aiming at developing renal protection against toxic side-effects of PRRT, we have characterized the pharmacokinetics and biodistribution of intravenously (i.v.) injected 125I- and non-labelled recombinant human A1M and the 111In- and fluorescence-labelled somatostatin analogue octreotide. Both molecules were predominantly localized to the kidneys, displaying a prevailing distribution in the cortex. A maximum of 76% of the injected A1M and 46% of the injected octreotide were present per gram kidney tissue at 10 to 20 minutes, respectively, after i.v. injection. Immunohistochemistry and fluorescence microscopy revealed a dominating co-existence of the two substances in proximal tubules, with a cellular co-localization in the epithelial cells. Importantly, analysis of kidney extracts displayed an intact, full-length A1M at least up to 60 minutes post-injection (p.i.). In summary, the results show a highly similar pharmacokinetics and biodistribution of A1M and octreotide, thus enabling the use of A1M to protect the kidneys tissue during PRRT. PMID:26269772

Evaluation of Renal Blood Flow in Chronic Kidney Disease Using Arterial Spin Labeling Perfusion Magnetic Resonance Imaging.

PubMed

Li, Lu-Ping; Tan, Huan; Thacker, Jon M; Li, Wei; Zhou, Ying; Kohn, Orly; Sprague, Stuart M; Prasad, Pottumarthi V

2017-01-01

Chronic kidney disease (CKD) is known to be associated with reduced renal blood flow. However, data to-date in humans is limited. In this study, non-invasive arterial spin labeling (ASL) MRI data was acquired in 33 patients with diabetes and stage-3 CKD, and 30 healthy controls. A significantly lower renal blood flow both in cortex (108.4±36.4 vs . 207.3±41.8; p<0.001, d=2.52) and medulla (23.2±8.9 vs . 42.6±15.8; p<0.001, d=1.5) was observed. Both cortical (ρ=0.67, p<0.001) and medullary (ρ=0.62, p<0.001) blood flow were correlated with eGFR, and cortical blood flow was found to be confounded by age and BMI. However, in a subset of subjects that were matched for age and BMI (n=6), the differences between CKD and control subjects remained significant both in cortex (107.4±42.8 vs . 187.51±20.44; p=0.002) and medulla (15.43±8.43 vs . 39.18±11.13; p=0.002). A threshold value to separate healthy and CKD was estimated to be Cor_BF=142.9 and Med_BF=24.1. These results support the use of ASL in the evaluation of renal blood flow in patients with moderate level of CKD. Whether these measurements can identify subjects at risk of progressive CKD requires further longitudinal follow-up.

Dynamic MRI-based computer aided diagnostic systems for early detection of kidney transplant rejection: A survey

NASA Astrophysics Data System (ADS)

Mostapha, Mahmoud; Khalifa, Fahmi; Alansary, Amir; Soliman, Ahmed; Gimel'farb, Georgy; El-Baz, Ayman

2013-10-01

Early detection of renal transplant rejection is important to implement appropriate medical and immune therapy in patients with transplanted kidneys. In literature, a large number of computer-aided diagnostic (CAD) systems using different image modalities, such as ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT), and radionuclide imaging, have been proposed for early detection of kidney diseases. A typical CAD system for kidney diagnosis consists of a set of processing steps including: motion correction, segmentation of the kidney and/or its internal structures (e.g., cortex, medulla), construction of agent kinetic curves, functional parameter estimation, diagnosis, and assessment of the kidney status. In this paper, we survey the current state-of-the-art CAD systems that have been developed for kidney disease diagnosis using dynamic MRI. In addition, the paper addresses several challenges that researchers face in developing efficient, fast and reliable CAD systems for the early detection of kidney diseases.

Quantitative Differences Between the First and Second Injection of Contrast Agent in Contrast-Enhanced Ultrasonography of Feline Kidneys and Spleen.

PubMed

Stock, Emmelie; Vanderperren, Katrien; Haers, Hendrik; Duchateau, Luc; Hesta, Myriam; Saunders, Jimmy H

2017-02-01

Contrast-enhanced ultrasound is a valuable and safe technique for the evaluation of organ perfusion. Repeated injections of ultrasound contrast agent are often administered during the same imaging session. However, it remains unclear if quantitative differences are present between the consecutive microbubble injections. Therefore, the first and second injection of contrast agent for the left renal cortex, renal medulla and the splenic parenchyma in healthy cats were compared. A lower peak intensity and area under the curve were observed for the first injection of contrast agent in the feline kidney, both for the renal cortex and medulla, and spleen. Moreover, for the renal cortex, the time-intensity curve was steeper after the second injection. Findings from the present study demonstrate that a second injection of contrast agent provides stronger enhancement. The exact mechanism behind our findings remains unclear; however, saturation of the lung macrophages is believed to play an important role. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Proteomic and phosphoproteomic analysis of renal cortex in a salt-load rat model of advanced kidney damage

PubMed Central

Jiang, Shaoling; He, Hanchang; Tan, Lishan; Wang, Liangliang; Su, Zhengxiu; Liu, Yufeng; Zhu, Hongguo; Zhang, Menghuan; Hou, Fan Fan; Li, Aiqing

2016-01-01

Salt plays an essential role in the progression of chronic kidney disease and hypertension. However, the mechanisms underlying pathogenesis of salt-induced kidney damage remain largely unknown. Here, Sprague-Dawley rats, that underwent 5/6 nephrectomy (5/6Nx, a model of advanced kidney damage) or sham operation, were treated for 2 weeks with a normal or high-salt diet. We employed aTiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for proteomic and phosphoproteomic profiling of the renal cortex. We found 318 proteins differentially expressed in 5/6Nx group relative to sham group, and 310 proteins significantly changed in response to salt load in 5/6Nx animals. Totally, 1810 unique phosphopeptides corresponding to 550 phosphoproteins were identified. We identified 113 upregulated and 84 downregulated phosphopeptides in 5/6Nx animals relative to sham animals. Salt load induced 78 upregulated and 91 downregulated phosphopeptides in 5/6Nx rats. The differentially expressed phospholproteins are important transporters, structural molecules, and receptors. Protein-protein interaction analysis revealed that the differentially phosphorylated proteins in 5/6Nx group, Polr2a, Srrm1, Gsta2 and Pxn were the most linked. Salt-induced differential phosphoproteins, Myh6, Lmna and Des were the most linked. Altered phosphorylation levels of lamin A and phospholamban were validated. This study will provide new insight into pathogenetic mechanisms of chronic kidney disease and salt sensitivity. PMID:27775022

Biodegradable nanoparticles for improved kidney bioavailability of rhein: preparation, characterization, plasma, and kidney pharmacokinetics.

PubMed

Wei, Yinghui; Luo, Xiaoting; Guan, Jiani; Ma, Jianping; Zhong, Yicong; Luo, Jingwen; Li, Fanzhu

2017-11-01

The aim of this work is to develop biodegradable nanoparticles for improved kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using an emulsification solvent evaporation method and fully characterized by several techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis probe in rat's kidney cortex. Blood samples were simultaneously collected (via femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles were small, with a mean particle size of 132.6 ± 5.95 nm, and homogeneously dispersed. The charge on the particles was nearly zero, the encapsulation efficiency was 62.71 ± 3.02%, and the drug loading was 1.56 ± 0.15%. In vitro release of RH from the nanoparticles showed an initial burst release followed by a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation of RH into nanoparticles significantly increased its kidney bioavailability (AUC kidney /AUC plasma  = 0.586 ± 0.072), clearly indicating that nanoparticles are a promising strategy for kidney drug delivery.

Multicystic dysplastic kidneys suggesting hydronephrosis during Tc-DTPA imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siddiqui, A.R.; Cohen, M.; Mitchell, M.E.

1982-10-01

Tc-99m DTPA renal scans on two infants with flank masses were interpreted as consistent with hydronephrosis and obstruction of the uretopelvic junction because of delayed accumulation of the radiotracer in the initially photon-deficient regions. However, both these patients were found to have multicystic dysplastic kidney. It appears that for proper diagnosis more attention should be paid to the location of the functioning cortex rather than to the delayed images.

Role of cytosolic NADP+-dependent isocitrate dehydrogenase in ischemia-reperfusion injury in mouse kidney.

PubMed

Kim, Jinu; Kim, Ki Young; Jang, Hee-Seong; Yoshida, Takumi; Tsuchiya, Ken; Nitta, Kosaku; Park, Jeen-Woo; Bonventre, Joseph V; Park, Kwon Moo

2009-03-01

Cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) synthesizes reduced NADP (NADPH), which is an essential cofactor for the generation of reduced glutathione (GSH), the most abundant and important antioxidant in mammalian cells. We investigated the role of IDPc in kidney ischemia-reperfusion (I/R) in mice. The activity and expression of IDPc were highest in the cortex, modest in the outer medulla, and lowest in the inner medulla. NADPH levels were greatest in the cortex. IDPc expression in the S1 and S2 segments of proximal tubules was higher than in the S3 segment, which is much more susceptible to I/R. IDPc protein was also highly expressed in the mitochondrion-rich intercalated cells of the collecting duct. IDPc activity was 10- to 30-fold higher than the activity of glucose-6-phosphate dehydrogenase, another producer of cytosolic NADPH, in various kidney regions. This study identifies that IDPc may be the primary source of NADPH in the kidney. I/R significantly reduced IDPc expression and activity and NADPH production and increased the ratio of oxidized glutathione to total glutathione [GSSG/(GSH+GSSG)], resulting in kidney dysfunction, tubular cell damage, and lipid peroxidation. In LLC-PK(1) cells, upregulation of IDPc by IDPc gene transfer protected the cells against hydrogen peroxide, enhancing NADPH production, inhibiting the increase of GSSG/(GSH+GSSG), and reducing lipid peroxidation. IDPc downregulation by small interference RNA treatment presented results contrasting with the upregulation. In conclusion, these results demonstrate that IDPc is expressed differentially along tubules in patterns that may contribute to differences in susceptibility to injury, is a major enzyme in cytosolic NADPH generation in kidney, and is downregulated with I/R.

Role of cytosolic NADP+-dependent isocitrate dehydrogenase in ischemia-reperfusion injury in mouse kidney

PubMed Central

Kim, Jinu; Kim, Ki Young; Jang, Hee-Seong; Yoshida, Takumi; Tsuchiya, Ken; Nitta, Kosaku; Park, Jeen-Woo; Bonventre, Joseph V.; Park, Kwon Moo

2009-01-01

Cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) synthesizes reduced NADP (NADPH), which is an essential cofactor for the generation of reduced glutathione (GSH), the most abundant and important antioxidant in mammalian cells. We investigated the role of IDPc in kidney ischemia-reperfusion (I/R) in mice. The activity and expression of IDPc were highest in the cortex, modest in the outer medulla, and lowest in the inner medulla. NADPH levels were greatest in the cortex. IDPc expression in the S1 and S2 segments of proximal tubules was higher than in the S3 segment, which is much more susceptible to I/R. IDPc protein was also highly expressed in the mitochondrion-rich intercalated cells of the collecting duct. IDPc activity was 10- to 30-fold higher than the activity of glucose-6-phosphate dehydrogenase, another producer of cytosolic NADPH, in various kidney regions. This study identifies that IDPc may be the primary source of NADPH in the kidney. I/R significantly reduced IDPc expression and activity and NADPH production and increased the ratio of oxidized glutathione to total glutathione [GSSG/(GSH+GSSG)], resulting in kidney dysfunction, tubular cell damage, and lipid peroxidation. In LLC-PK1 cells, upregulation of IDPc by IDPc gene transfer protected the cells against hydrogen peroxide, enhancing NADPH production, inhibiting the increase of GSSG/(GSH+GSSG), and reducing lipid peroxidation. IDPc downregulation by small interference RNA treatment presented results contrasting with the upregulation. In conclusion, these results demonstrate that IDPc is expressed differentially along tubules in patterns that may contribute to differences in susceptibility to injury, is a major enzyme in cytosolic NADPH generation in kidney, and is downregulated with I/R. PMID:19106211

Pharmacological evaluation of an [(123)I] labelled imidazopyridine-3-acetamide for the study of benzodiazepine receptors.

PubMed

Mattner, Filomena; Mardon, Karine; Loc'h, Christian; Katsifis, Andrew

2006-06-13

In vitro binding of the iodinated imidazopyridine, N',N'-dimethyl-6-methyl-(4'-[(123)I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide [(123)I]IZOL to benzodiazepine binding sites on brain cortex, adrenal and kidney membranes is reported. Saturation experiments showed that [(123)I]IZOL, bound to a single class of binding site (n(H)=0.99) on adrenal and kidney mitochondrial membranes with a moderate affinity (K(d)=30 nM). The density of binding sites was 22+/-6 and 1.2+/-0.4 pmol/mg protein on adrenal and kidney membranes, respectively. No specific binding was observed in mitochondrial-synaptosomal membranes of brain cortex. In biodistribution studies in rats, the highest uptake of [(123)I]IZOL was found 30 min post injection in adrenals (7.5% ID/g), followed by heart, kidney, lung (1% ID/g) and brain (0.12% ID/g), consistent with the distribution of peripheral benzodiazepine binding sites. Pre-administration of unlabelled IZOL and the specific PBBS drugs, PK 11195 and Ro 5-4864 significantly reduced the uptake of [(123)I]IZOL by 30% (p<0.05) in olfactory bulbs and by 51-86% (p<0.01) in kidney, lungs, heart and adrenals, while it increased by 30% to 50% (p<0.01) in the rest of the brain and the blood. Diazepam, a mixed CBR-PBBS drug, inhibited the uptake in kidney, lungs, heart, adrenals and olfactory bulbs by 32% to 44% (p<0.01) but with no effect on brain uptake and in blood concentration. Flumazenil, a central benzodiazepine drug and haloperidol (dopamine antagonist/sigma receptor drug) displayed no effect in [(123)I]IZOL in peripheral organs and in the brain. [(123)I]IZOL may deserve further development for imaging selectively peripheral benzodiazepine binding sites.

Selenium-binding protein 1: a sensitive urinary biomarker to detect heavy metal-induced nephrotoxicity.

PubMed

Lee, Eui Kyung; Shin, Young-Jun; Park, Eun Young; Kim, Nam Deuk; Moon, Aree; Kwack, Seung Jun; Son, Ji Yeon; Kacew, Sam; Lee, Byung Mu; Bae, Ok-Nam; Kim, Hyung Sik

2017-04-01

Identifying novel biomarkers to detect nephrotoxicity is clinically important. Here, we attempted to identify new biomarkers for mercury-induced nephrotoxicity and compared their sensitivity to that of traditional biomarkers in animal models. Comparative proteomics analysis was performed in kidney tissues of Sprague-Dawley rats after oral treatment with HgCl 2 (0.1, 1, or 5 mg/kg/day) for 21 days. Kidney cortex tissues were analyzed by two-dimensional gel electrophoresis/matrix-assisted laser desorption/ionization, and differentially expressed proteins were identified. The corresponding spots were quantitated by RT-PCR. Selenium-binding protein 1 (SBP1) was found to be the most markedly upregulated protein in the kidney cortex of rats after HgCl 2 administration. However, blood urea nitrogen, serum creatinine, and glucose levels increased significantly only in the 1 or 5 mg/kg HgCl 2 -treated groups. A number of urinary excretion proteins, including kidney injury molecule-1, clusterin, monocyte chemoattractant protein-1, and β-microglobulin, increased dose-dependently. Histopathological examination revealed severe proximal tubular damage in high-dose (5 mg/kg) HgCl 2 -exposed groups. In addition, urinary excretion of SBP1 significantly increased in a dose-dependent manner. To confirm the critical role of SBP1 as a biomarker for nephrotoxicity, normal kidney proximal tubular cells were treated with HgCl 2 , CdCl 2 , or cisplatin for 24 h. SBP1 levels significantly increased in conditioned media exposed to nephrotoxicants, but decreased in cell lysates. Our investigations suggest that SBP1 may play a critical role in the pathological processes underlying chemical-induced nephrotoxicity. Thus, urinary excretion of SBP1 might be a sensitive and specific biomarker to detect early stages of kidney injury.

Fluoride potentiates tubulointerstitial nephropathy caused by unilateral ureteral obstruction.

PubMed

Kido, Takamasa; Tsunoda, Masashi; Sugaya, Chiemi; Hano, Hiroshi; Yanagisawa, Hiroyuki

2017-12-01

The contamination of ground water by fluoride has been reported worldwide. Most fluoride (approximately 70%) is filtered by the kidneys; humans or experimental animals with renal damage therefore may be more affected by fluoride exposure than those with normal kidney function. Tubulointerstitial fibrosis, which involves macrophage-promoted extracellular matrix production and myofibroblast migration, can be induced in rats by unilateral ureteral obstruction (UUO). We examined the effects of fluoride exposure on tubulointerstitial fibrosis in the obstructed kidney of UUO rats. The left ureters of 6-week-old male rats were ligated using silk sutures. Fluoride was then administered for 2 weeks at doses of 0, 75, and 150ppm in the drinking water. Real-time polymerase chain reaction was performed to analyze transforming growth factor beta 1 (TGF-β 1 ) transcription; histological and immunohistochemical staining were used to identify positive areas within the renal cortex and staining-positive cells by image analysis. Significant increases were observed in the obstructed kidneys of UUO rats exposed to 150ppm fluoride (compared to 0ppm) for areas or number of cells that stained with Masson trichrome or with antibodies against collagen type I, alpha-smooth muscle actin (α-SMA, a myofibroblast marker), ED1, ED2, and ED3 (macrophage markers), and TGF-β 1 . Taken together, these observations suggested that fluoride exacerbates tuburointerstitial nephropathy resulting from UUO, and that this effect occurs via activation of the M2 macrophage-TGF-β1-fibroblast/myofibroblast-collagen synthesis pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic kidney disease: Pathological and functional evaluation with intravoxel incoherent motion diffusion-weighted imaging.

PubMed

Mao, Wei; Zhou, Jianjun; Zeng, Mengsu; Ding, Yuqin; Qu, Lijie; Chen, Caizhong; Ding, Xiaoqiang; Wang, Yaqiong; Fu, Caixia

2018-05-01

Because chronic kidney disease (CKD) is a worldwide problem, accurate pathological and functional evaluation is required for planning treatment and follow-up. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can assess both capillary perfusion and tissue diffusion and may be helpful in evaluating renal function and pathology. To evaluate functional and pathological alterations in CKD by applying IVIM-DWI. Prospective study. In all, 72 CKD patients who required renal biopsy and 20 healthy volunteers. 1.5T. All subjects underwent IVIM-DWI of the kidneys, and image analysis was performed by two radiologists. The mean values of true diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f) were acquired from renal parenchyma. Correlation between IVIM-DWI parameters and estimated glomerular filtration rate (eGFR), as well as pathological damage, were assessed. One-way analysis of variance (ANOVA), paired sample t-test and Spearman correlation analysis. The paired sample t-test revealed that IVIM-DWI parameters were significantly lower in medulla than cortex for both patients and controls (P < 0.01). Regardless of whether eGFR was reduced, ANOVA revealed that f values of renal parenchyma were significantly lower in patients than controls (P < 0.05). Spearman correlation analysis revealed that there were positive correlations between eGFR and D (cortex, r = 0.466, P < 0.001; medulla, r = 0.491, P < 0.001), and between eGFR and f (cortex, r = 0.713, P < 0.001; medulla, r = 0.512, P < 0.001). Negative correlations were found between f and glomerular injury (cortex, r = -0.773, P < 0.001; medulla, r = -0.629, P < 0.001), and between f and tubulointerstitial lesion (cortex, r = -0.728, P < 0.001; medulla, r = -0.547, P < 0.001). IVIM-DWI might be feasible for noninvasive evaluation of renal function and pathology of CKD, especially in detection of renal insufficiency at an early stage. 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1251-1259. © 2017 International Society for Magnetic Resonance in Medicine.

Characteristics of (3H)2-Deoxyglucose Uptake by Slices of Rat Cerebral Cortex

DTIC Science & Technology

1983-05-17

phlorizin or by phloretin , two compounds known to inhibit glucose transport by kidney and by erythrocytes, respectively. Net [-̂ H]2-de- oxyglucose uptake...Hexoses 53 17. The Effect of Phlorizin and Phloretin on Net [3H]2-Deoxy- glucose Transport by Slices of Cerebral Cortex 55 18. The Effect of Sodium...LeFevre, 1961). Transport by erythrocytes is not dependent on sodium (Silverman, 1976). Transport is, however, sensitive to inhibition by phloretin

Concise Review: Kidney Generation with Human Pluripotent Stem Cells.

PubMed

Morizane, Ryuji; Miyoshi, Tomoya; Bonventre, Joseph V

2017-11-01

Chronic kidney disease (CKD) is a worldwide health care problem, resulting in increased cardiovascular mortality and often leading to end-stage kidney disease, where patients require kidney replacement therapies such as hemodialysis or kidney transplantation. Loss of functional nephrons contributes to the progression of CKD, which can be attenuated but not reversed due to inability to generate new nephrons in human adult kidneys. Human pluripotent stem cells (hPSCs), by virtue of their unlimited self-renewal and ability to differentiate into cells of all three embryonic germ layers, are attractive sources for kidney regenerative therapies. Recent advances in stem cell biology have identified key signals necessary to maintain stemness of human nephron progenitor cells (NPCs) in vitro, and led to establishment of protocols to generate NPCs and nephron epithelial cells from human fetal kidneys and hPSCs. Effective production of large amounts of human NPCs and kidney organoids will facilitate elucidation of developmental and pathobiological pathways, kidney disease modeling and drug screening as well as kidney regenerative therapies. We summarize the recent studies to induce NPCs and kidney cells from hPSCs, studies of NPC expansion from mouse and human embryonic kidneys, and discuss possible approaches in vivo to regenerate kidneys with cell therapies and the development of bioengineered kidneys. Stem Cells 2017;35:2209-2217. © 2017 AlphaMed Press.

Liquid chromatography-mass spectrometry-based metabolomics and lipidomics reveal toxicological mechanisms of bisphenol F in breast cancer xenografts.

PubMed

Zhao, Chao; Xie, Peisi; Wang, Hailin; Cai, Zongwei

2018-05-05

Bisphenol F (BPF) is a major alternative to bisphenol (BPA) and has been widely used. Although BPA exposure is known to generate various toxic effects, toxicity of BPF remains under-explored. A comprehensive method involving mass spectrometry (MS)-based global lipidomics and metabolomics, and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI)- MS imaging (MSI) was used to study toxic effects of BPF and the underlying mechanisms on tumor metastasis-related tissues (liver and kidney) in breast cancer xenografts. Our results demonstrated that BPF exposure disturbed the metabolome and lipidome of liver and kidney. Exposure induced reprogramming of the glutathione (GSH) biosynthesis and glycolytic metabolism by activating glycine, serine, cysteine, glutamine, lactate and pyruvate in liver and kidney tissues. It also perturbed the biosynthesis and degradation of glycerophospholipids (GPs) and glycerolipids (GLs), resulting in abnormality of membrane homeostasis and cellular functions in kidney tissues. Moreover, spatial distribution and profile of metabolites changed across renal cortex and medulla regions after BPF treatment. Levels of phosphatidylethanolamines (PE) and triacylglycerols (TAG) increased in renal medulla and pelvis, while the levels of phosphatidylcholines (PC) and phosphatidylinositols (PI) increased in cortex and pelvis. These observations offer a deeper understanding of critical role of metabolites and lipid reprogramming in BPF-induced biological effects. Copyright © 2018 Elsevier B.V. All rights reserved.

Kidney outer medulla mitochondria are more efficient compared to cortex mitochondria as a strategy to sustain ATP production in a suboptimal environment.

PubMed

Schiffer, Tomas A; Gustafsson, Håkan; Palm, Fredrik

2018-05-30

The kidneys receive approximately 25% of cardiac output, which is a prerequisite in order to maintain sufficient glomerular filtration rate. However, both intrarenal regional renal blood flow and tissue oxygen levels are heterogeneous with decreasing levels in the inner part of the medulla. These differences in combination with the heterogeneous metabolic activity of the different nephron segment located in the different parts of the kidney may constitute a functional problem when challenged. The proximal tubule and the medullary thick ascending limb of Henle are considered to have the highest metabolic rate, which is relating to the high mitochondria content needed to sustain sufficient ATP production from oxidative phosphorylation in order to support high electrolyte transport activity in these nephron segments. Interestingly, the cells located in kidney medulla functions at the verge of hypoxia and the mitochondria may have adapted to the surrounding environment. However, little is known about intrarenal differences in mitochondria function. We therefore investigated functional differences between mitochondria isolated from kidney cortex and medulla of healthy normoglycemic rats were estimated using high-resolution respirometry. The results demonstrate that medullary mitochondria had a higher degree of coupling, are more efficient and have higher oxygen affinity, which would make them more suitable to function in an environment with limited oxygen supply. Furthermore, these results support the hypothesis that mitochondria of medullary cells have adapted to the normal hypoxic in vivo situation as a strategy of sustaining ATP production in a suboptimal environment.

Performance of U-net based pyramidal lucas-kanade registration on free-breathing multi-b-value diffusion MRI of the kidney.

PubMed

Lv, Jun; Huang, Wenjian; Zhang, Jue; Wang, Xiaoying

2018-06-01

In free-breathing multi-b-value diffusion-weighted imaging (DWI), a series of images typically requires several minutes to collect. During respiration the kidney is routinely displaced and may also undergo deformation. These respiratory motion effects generate artifacts and these are the main sources of error in the quantification of intravoxel incoherent motion (IVIM) derived parameters. This work proposes a fully automated framework that combines a kidney segmentation to improve the registration accuracy. 10 healthy subjects were recruited to participate in this experiment. For the segmentation, U-net was adopted to acquire the kidney's contour. The segmented kidney then served as a region of interest (ROI) for the registration method, known as pyramidal Lucas-Kanade. Our proposed framework confines the kidney's solution range, thus increasing the pyramidal Lucas-Kanade's accuracy. To demonstrate the feasibility of our presented framework, eight regions of interest were selected in the cortex and medulla, and data stability was estimated by comparing the normalized root-mean-square error (NRMSE) values of the fitted data from the bi-exponential intravoxel incoherent motion model pre- and post- registration. The results show that the NRMSE was significantly lower after registration both in the cortex (p < 0.05) and medulla (p < 0.01) during free-breathing measurements. In addition, expert visual scoring of the derived apparent diffusion coefficient (ADC), f, D and D* maps indicated there were significant improvements in the alignment of the kidney in the post-registered image. The proposed framework can effectively reduce the motion artifacts of misaligned multi-b-value DWIs and the inaccuracies of the ADC, f, D and D* estimations. Advances in knowledge: This study demonstrates the feasibility of our proposed fully automated framework combining U-net based segmentation and pyramidal Lucas-Kanade registration method for improving the alignment of multi-b-value diffusion-weighted MRIs and reducing the inaccuracy of parameter estimation during free-breathing.

Adrenocortical Carcinoma—Patient Version

Cancer.gov

Adrenocortical carcinoma is a rare cancer which forms in the cortex (outer layer) of an adrenal gland. There are two adrenal glands. One sits on top of each kidney. Start here to find information on adrenocortical carcinoma treatment and research.

Concentration gradient of oxalate from cortex to papilla in rat kidney.

PubMed

Nakatani, Tatsuya; Ishii, Keiichi; Sugimoto, Toshikado; Kamikawa, Sadanori; Yamamoto, Keisuke; Yoneda, Yukio; Kanazawa, Toshinao; Kishimoto, Taketoshi

2003-02-01

The kidney eliminates the major fraction of plasma oxalate. It is well known that oxalate is freely filtered by glomeruli and secreted by the proximal tubules. However, the renal handling of oxalate in distal nephrons, which is considered as playing an important role in stone formation, remains obscure. At 15-180 min after intravenous injection of 14C-oxalate to rats, the intrarenal localization of radioactivity was quantitatively measured by the radioluminographic method using a bioimaging analyzer. Tissue radioactivity was compared with plasma, and urinary radioactivities were measured by a liquid scintillation counter. The control study was conducted with 14C-inulin. The radioactivity of 14C-oxalate in the papilla was 10 times greater than in the cortex and eight times greater than in the medulla 180 min after injection when almost no radioactivity was present in the urine. In contrast, the radioactivity of 14C-inulin was nine times less in the papilla than in the cortex at the same time. Oxalate remains in the renal papilla for an extended period. This accumulation of oxalate may be attributed to calcium oxalate crystal fixation along the deep nephron which is considered to be the first step of stone formation.

DIFFUSION-WEIGHTED IMAGING TRACTOGRAPHY-BASED PARCELLATION OF THE HUMAN PARIETAL CORTEX AND COMPARISON WITH HUMAN AND MACAQUE RESTING STATE FUNCTIONAL CONNECTIVITY

PubMed Central

Mars, Rogier B.; Jbabdi, Saad; Sallet, Jérôme; O’Reilly, Jill X.; Croxson, Paula L.; Olivier, Etienne; Noonan, MaryAnn P.; Bergmann, Caroline; Mitchell, Anna S.; Baxter, Mark G.; Behrens, Timothy E.J.; Johansen-Berg, Heidi; Tomassini, Valentina; Miller, Karla L.; Rushworth, Matthew F.S.

2011-01-01

Despite the prominence of parietal activity in human neuromaging investigations of sensorimotor and cognitive processes there remains uncertainty about basic aspects of parietal cortical anatomical organization. Descriptions of human parietal cortex draw heavily on anatomical schemes developed in other primate species but the validity of such comparisons has been questioned by claims that there are fundamental differences between the parietal cortex in humans and other primates. A scheme is presented for parcellation of human lateral parietal cortex into component regions on the basis of anatomical connectivity and the functional interactions of the resulting clusters with other brain regions. Anatomical connectivity was estimated using diffusion-weighted magnetic resonance image (MRI) based tractography and functional interactions were assessed by correlations in activity measured with functional MRI (fMRI) at rest. Resting state functional connectivity was also assessed directly in the rhesus macaque lateral parietal cortex in an additional experiment and the patterns found reflected known neuroanatomical connections. Cross-correlation in the tractography-based connectivity patterns of parietal voxels reliably parcellated human lateral parietal cortex into ten component clusters. The resting state functional connectivity of human superior parietal and intraparietal clusters with frontal and extrastriate cortex suggested correspondences with areas in macaque superior and intraparietal sulcus. Functional connectivity patterns with parahippocampal cortex and premotor cortex again suggested fundamental correspondences between inferior parietal cortex in humans and macaques. In contrast, the human parietal cortex differs in the strength of its interactions between the central inferior parietal lobule region and the anterior prefrontal cortex. PMID:21411650

The Effect of Diazoxide Upon Heat Shock Protein and Physiological Response to Hemorrhagic Shock and Cerebral Stroke

DTIC Science & Technology

2006-06-16

ischemic kidney model [121]. Photothrombic brain injury elicits the expression of HSP70 and HSP27 . HSP70 expression as early as one hour post-trauma...delineated the area of necrosis at 24 hours post-thrombic injury in ipsilateral cortex. HSP27 expression also was found to be upregulated and in fact...more globally expressed in the entire ipsilateral cerebral cortex, primarily in astrocytes [122]. 25 HSP25 and HSP27 Research demonstrates

Anatomic and physiologic changes of the aging kidney.

PubMed

Karam, Zeina; Tuazon, Jennifer

2013-08-01

Aging is associated with structural and functional changes in the kidney. Structural changes include glomerulosclerosis, thickening of the basement membrane, increase in mesangial matrix, tubulointerstitial fibrosis and arteriosclerosis. Glomerular filtration rate is maintained until the fourth decade of life, after which it declines. Parallel reductions in renal blood flow occur with redistribution of blood flow from the cortex to the medulla. Other functional changes include an increase in glomerular basement permeability and decreased ability to dilute or concentrate urine. Copyright © 2013 Elsevier Inc. All rights reserved.

Glucagon-like peptide 1 receptor expression in primary porcine proximal tubular cells.

PubMed

Schlatter, P; Beglinger, C; Drewe, J; Gutmann, H

2007-06-07

GLP-1 is secreted into the circulation after food intake. The main biological effects of GLP-1 include stimulation of glucose dependent insulin secretion and induction of satiety feelings. Recently, it was demonstrated in rats and humans that GLP-1 can stimulate renal excretion of sodium. Based on these data, the existence of a renal GLP-1 receptor (GLP-1R) was postulated. However, the exact localization of the GLP-1R and the mechanism of this GLP-1 action have not yet been investigated. Primary porcine proximal tubular cells were isolated from porcine kidneys. Expression of GLP-1R was measured at the mRNA level by quantitative RT-PCR. Protein expression of GLP-1R was verified with immunocytochemistry, immunohistochemistry and Western blot analysis. Functional studies included transport assessments of sodium and glucose using three different GLP-1 concentrations (200 pM, 2 nM and 20 nM), 200 pM exendin-4 (GLP-1 analogue) and an inhibitor of the dipeptidylpeptidase IV (DPPIV) enzyme (P32/98 at 10 microM). Finally, the expression of NHE3, the predominant Na(+)/H(+) exchanger in proximal tubular cells, was also investigated. GLP-1R, NHE3 and DPPIV were expressed at the mRNA level in porcine proximal tubular kidney cells. GLP-1R expression was confirmed at the protein level. Staining of human and pig kidney cortex revealed that GLP-1R was predominantly expressed in proximal tubular cells. Functional assays demonstrated an inhibition of sodium re-absorption with GLP-1 after 3 h of incubation. Exendin-4 and GLP-1 in combination with P32/98 co-administration had no clear influence on glucose and sodium uptake and transport. GLP-1R is functionally expressed in porcine proximal tubular kidney cells. Addition of GLP-1 to these cells resulted in a reduced sodium re-absorption. GLP-1 had no effect on glucose re-absorption. We conclude that GLP-1 modulates sodium homeostasis in the kidney most likely through a direct action via its GLP-1R in proximal tubular cells.

Treatment with the matricellular protein CCN3 blocks and/or reverses fibrosis development in obesity with diabetic nephropathy.

PubMed

Riser, Bruce L; Najmabadi, Feridoon; Garchow, Kendra; Barnes, Jeffrey L; Peterson, Darryl R; Sukowski, Ernest J

2014-11-01

Fibrosis is at the core of the high morbidity and mortality rates associated with the complications of diabetes and obesity, including diabetic nephropathy (DN), without any US Food and Drug Administration-approved drugs with this specific target. We recently provided the first evidence that the matricellular protein CCN3 (official symbol NOV) functions in a reciprocal manner, acting on the profibrotic family member CCN2 to inhibit fibrosis in a mesangial cell model of DN. Herein, we used the BT/BR ob/ob mouse as a best model of human obesity and DN progression to determine whether recombinant human CCN3 could be used therapeutically, and the mechanisms involved. Eight weeks of thrice-weekly i.p. injections (0.604 and 6.04 μg/kg of recombinant human CCN3) beginning in early-stage DN completely blocked and/or reversed the up-regulation of mRNA expression of kidney cortex fibrosis genes (CCN2, Col1a2, TGF-β1, and PAI-1) seen in placebo-treated diabetic mice. The treatment completely blocked glomerular fibrosis, as determined by altered mesangial expansion and deposition of laminin. Furthermore, it protected against, or reversed, podocyte loss and kidney function reduction (rise in plasma creatinine concentration); albuminuria was also greatly reduced. This study demonstrates the potential efficacy of recombinant human CCN3 treatment in DN and points to mechanisms operating at multiple levels or pathways, upstream (eg, protecting against cell injury) and downstream (eg, regulating CCN2 activity and extracellular matrix metabolism).

Conserved and Divergent Features of Human and Mouse Kidney Organogenesis.

PubMed

Lindström, Nils O; McMahon, Jill A; Guo, Jinjin; Tran, Tracy; Guo, Qiuyu; Rutledge, Elisabeth; Parvez, Riana K; Saribekyan, Gohar; Schuler, Robert E; Liao, Christopher; Kim, Albert D; Abdelhalim, Ahmed; Ruffins, Seth W; Thornton, Matthew E; Basking, Laurence; Grubbs, Brendan; Kesselman, Carl; McMahon, Andrew P

2018-03-01

Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34-37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4-23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species. Copyright © 2018 by the American Society of Nephrology.

Comparison of different agar diffusion methods for the detection of residues in the kidneys of pigs treated with antimicrobial drugs.

PubMed

Korkeala, H; Sorvettula, O; Mäki-Petäys, O; Hirn, J

1983-01-01

Residue analyses of the kidneys of twenty-six pigs treated with various antimicrobial drugs 20 h before slaughter and of eleven untreated pigs were performed. The effects of storage temperature of the kidneys, and of sampling location, on the residue analysis were also studied. No method alone was sufficient for the detection of residues. Oxytetracycline residues could be detected at pH 6, dihydrostreptomycin residues at pH 8, and sulphonamide residues if trimethoprim was present in the medium. Chloramphenicol, penicillin G procaine, tylosin and lincomycin residues were not detectable with the methods used. The concentration of ampicillin decreased during the storage of samples at +4°C. Most methods also yielded zones of inhibition for the frozen kidneys from untreated pigs. It seems necessary to use agar media of two different pH values: the addition of trimethoprim to the medium is also needed. The use of fresh pig kidneys, and samples containing both kidney medulla and kidney cortex, is recommended in residue analysis. Copyright © 1983. Published by Elsevier Ltd.

The effect of zinc on healing of renal damage in rats.

PubMed

Salehipour, Mehdi; Monabbati, Ahmad; Ensafdaran, Mohammad Reza; Adib, Ali; Babaei, Amir Hossein

2017-07-01

Several studies have previously been performed to promote kidney healing after injuries. Objectives: The aim of this study was to investigate the effect of zinc on renal healing after traumatic injury in rats. Forty healthy female rats were selected and one of their kidneys was incised. Half of the incisions were limited only to the cortex (renal injury type I) and the other ones reached the pelvocalyceal system of the kidney (renal injury type II). All the rats in the zinc treated group (case group) received 36.3 mg zinc sulfate (contained 8.25 mg zinc) orally. After 28 days, the damaged kidneys were removed for histopathological studies. In the rats with type I injury, kidney inflammation of the case group was significantly lower than that of the control group. However, the result was not significant in rats with type II injury. Tissue loss and granulation tissue formation were significantly lower in the case group than the control group in both type I and II kidney injuries. Overall, Zinc can contribute to better healing of the rat's kidneys after a traumatic injury.

Nutrition and lysosomal activity

PubMed Central

Moore, T.; Sharman, I. M.; Stanton, M. G.; Dingle, J. T.

1967-01-01

1. Experiments on rats were made to find whether the increased liability of the kidney-cortex tubules to autolysis post mortem, which is a well-established abnormality in vitamin E deficiency, can be correlated with changes in lysosomal activity. Parallel observations were made on the development of certain other abnormalities characteristic of avitaminosis E. 2. In rats killed after long periods (8–10 months) of subsistence on a standard vitamin E-deficient diet, containing lard, both the rate of kidney autolysis post mortem and the enzyme activity of lysosome preparations from the fresh tissues were much greater than in controls. A greater percentage difference was usually found in the `free' enzyme fraction than in `bound' or `total' activity. 3. In rats killed after graded periods (3–8 months) of deficiency, two abnormalities (decreased resistance of the erythrocytes to haemolysis, and brown discoloration of the uterus) were already evident at a stage (3–4 months) when the liability to rapid kidney autolysis had not begun. At this point the enzymic activity of kidney extracts differed little between deficient animals and controls given α-tocopherol. As the duration of deficiency advanced, parallel increases occurred in the rate of kidney autolysis and in lysosomal instability. 4. When cod-liver oil, rich in polyunsaturated fatty acids but freed from vitamin A, was substituted for lard in the diet, the time (1½ months) required for the inducement of both rapid kidney autolysis and decreased lysosomal stability was greatly shortened. The time for the inducement of brown discoloration of the uterus was not shortened and the kidney abnormalities appeared while the uterus was still normal. 5. Confirmation was thus obtained for the view that the various tissues of the rat respond differently to the relationship between the adequacy of the vitamin E status and the intake of polyunsaturated fatty acids. The kidney-cortex tubules, as evidenced by autolysis post mortem and the corresponding decrease in lysosomal stability, may be classed among those tissues that are most sensitive to the effect of high intakes of polyunsaturated acids. PMID:6049409

Determination of spatial distribution of melamine-cyanuric acid crystals in rat kidney tissue by histology and imaging matrix-assisted laser desorption/ionization quadrupole time-of-flight mass spectrometry.

PubMed

Kim, Chae-Wook; Yun, Jun-Won; Bae, Il-Hong; Lee, Joon-Seok; Kang, Hyun-Jin; Joo, Kyung-Mi; Jeong, Hye-Jin; Chung, Jin-Ho; Park, Young-Ho; Lim, Kyung-Min

2010-01-01

After the outbreak of acute renal failure associated with melamine-contaminated pet food, many attempts have been made to uncover the mechanism underlying the renal toxicity caused by melamine and melamine-related compounds. Using rat models, we investigated the renal crystal formation following the ingestion of a melamine-cyanuric acid mixture (M+CA, 1:1) to gain insight into the M+CA-induced renal toxicity. M+CA did not induce toxicity in precision-cut kidney slices, suggesting that M+CA does not have a direct nephrotoxicity. On the contrary, oral administration of M+CA for 3 days induced nephrotoxicity as determined by increased serum blood urea nitrogen and creatinine, reduced creatinine clearance, and enlarged kidneys in the animals treated with 50 mg/kg M+CA (melamine, 25 mg/kg, and cyanuric acid, 25 mg/kg; 2 of 10 animals) and 100 mg/kg M+CA (9 of 9 animals). While urine crystals were found in all animals treated with M+CA (25-100 mg/kg), histological examination revealed that renal crystals could be observed only in the kidneys of animals showing signs of nephrotoxicity. Remarkably, at 50 mg/kg M+CA, crystals were observed mainly in the medulla region of the kidney, while at 100 mg/kg, crystals were disseminated throughout the cortex and medulla regions. To further investigate the crystal formation by M+CA, matrix-assisted laser desorption/ionization quadrupole time-of-flight (MALDI-Q-TOF) imaging mass spectrometry detecting melamine distribution through monitoring the product ion (m/z 85, M + H) from melamine (m/z 127, M + H) was developed to directly obtain the image of melamine distribution in the kidney. The distribution image of melamine in kidney tissue confirmed that dense points of melamine were located only in the medulla region at 50 mg/kg M+CA, while at 100 mg/kg, they were disseminated widely from the cortex to medulla. These results demonstrated that M+CA ingestion could lead to crystal formation in kidney tubules along the osmotic gradient and that renal crystal formation is closely linked with M+CA-induced nephrotoxicity.

Expression of a functional asialoglycoprotein receptor in human renal proximal tubular epithelial cells.

PubMed

Seow, Ying-ying T; Tan, Michelle G K; Woo, Keng Thye

2002-07-01

The asialoglycoprotein receptor (ASGPR) is a C lectin which binds and endocytoses serum glycoproteins. In humans, the ASGPR is shown mainly to occur in hepatocytes, but does occur extrahepatically in thyroid, in small and large intestines, and in the testis. In the kidney, there has been evidence both for and against its existence in mesangial cells. Standard light microscopy examination of renal tissue stained with an antibody against the ASGPR was performed. The mRNA expression for the ASGPR H1 and H2 subunits in primary human renal proximal tubular epithelial cells (RPTEC), in the human proximal tubular epithelial cell line HK2, and in human renal cortex was investigated using reverse-transcribed nested polymerase chain reaction. ASGPR protein expression as well as ligand binding and uptake were also examined using confocal microscopy and flow cytometry (fluorescence-activated cell sorting). Light microscopy of paraffin renal biopsy sections stained with a polyclonal antibody against the ASGPR showed proximal tubular epithelial cell staining of the cytoplasm and particularly in the basolateral region. Renal cortex and RPTEC specifically have mRNA for both H1 and H2 subunits of the ASGPR, but HK2 only expresses mRNA for H1. Using a monoclonal antibody, the presence of the ASGPR in RPTEC was shown by fluorescence-activated cell sorting and immunofluorescent staining. Specific binding and uptake of fluorescein isothiocyanate labelled asialofetuin which is a specific ASGPR ligand was also demonstrated in RPTEC. Primary renal proximal tubular epithelial cells have a functional ASGPR, consisting of the H1 and H2 subunits, that is capable of specific ligand binding and uptake. Copyright 2002 S. Karger AG, Basel

Mitogen-Activated Protein Kinase 14 Promotes AKI

PubMed Central

Husi, Holger; Gonzalez-Lafuente, Laura; Valiño-Rivas, Lara; Fresno, Manuel; Sanz, Ana Belen; Mullen, William; Albalat, Amaya; Mezzano, Sergio; Vlahou, Tonia; Mischak, Harald

2017-01-01

An improved understanding of pathogenic pathways in AKI may identify novel therapeutic approaches. Previously, we conducted unbiased liquid chromatography-tandem mass spectrometry–based protein expression profiling of the renal proteome in mice with acute folate nephropathy. Here, analysis of the dataset identified enrichment of pathways involving NFκB in the kidney cortex, and a targeted data mining approach identified components of the noncanonical NFκB pathway, including the upstream kinase mitogen-activated protein kinase kinase kinase 14 (MAP3K14), the NFκB DNA binding heterodimer RelB/NFκB2, and proteins involved in NFκB2 p100 ubiquitination and proteasomal processing to p52, as upregulated. Immunohistochemistry localized MAP3K14 expression to tubular cells in acute folate nephropathy and human AKI. In vivo, kidney expression levels of NFκB2 p100 and p52 increased rapidly after folic acid injection, as did DNA binding of RelB and NFκB2, detected in nuclei isolated from the kidneys. Compared with wild-type mice, MAP3K14 activity–deficient aly/aly (MAP3K14aly/aly) mice had less kidney dysfunction, inflammation, and apoptosis in acute folate nephropathy and less kidney dysfunction and a lower mortality rate in cisplatin-induced AKI. The exchange of bone marrow between wild-type and MAP3K14aly/aly mice did not affect the survival rate of either group after folic acid injection. In cultured tubular cells, MAP3K14 small interfering RNA targeting decreased inflammation and cell death. Additionally, cell culture and in vivo studies identified the chemokines MCP-1, RANTES, and CXCL10 as MAP3K14 targets in tubular cells. In conclusion, MAP3K14 promotes kidney injury through promotion of inflammation and cell death and is a promising novel therapeutic target. PMID:27620989

Renal oxygen content is increased in healthy subjects after angiotensin-converting enzyme inhibition.

PubMed

Stein, Anna; Goldmeier, Silvia; Voltolini, Sarah; Setogutti, Enio; Feldman, Carlos; Figueiredo, Eduardo; Eick, Renato; Irigoyen, Maria; Rigatto, Katya

2012-07-01

The association between renal hypoxia and the development of renal injury is well established. However, no adequate method currently exists to non-invasively measure functional changes in renal oxygenation in normal and injured patients. R2* quantification was performed using renal blood oxygen level-dependent properties. Five healthy normotensive women (50 ± 5.3 years) underwent magnetic resonance imaging in a 1.5T Signa Excite HDx scanner (GE Healthcare, Waukesha, WI). A multiple fast gradient-echo sequence was used to acquire R2*/T2* images (sixteen echoes from 2.1 ms/slice to 49.6 ms/slice in a single breath hold per location). The images were post-processed to generate R2* maps for quantification. Data were recorded before and at 30 minutes after the oral administration of an angiotensin II-converting enzyme inhibitor (captopril, 25 mg). The results were compared using an ANOVA for repeated measurements (mean + standard deviation) followed by the Tukey test. ClinicalTrials.gov: NCT01545479. A significant difference (p<0.001) in renal oxygenation (R2*) was observed in the cortex and medulla before and after captopril administration: right kidney, cortex = 11.08 ± 0.56 ms, medulla = 17.21 ± 1.47 ms and cortex = 10.30 ± 0.44 ms, medulla = 16.06 ± 1.74 ms, respectively; and left kidney, cortex= 11.79 ± 1.85 ms, medulla = 17.03 ± 0.88 ms and cortex = 10.89 ± 0.91 ms, medulla = 16.43 ± 1.49 ms, respectively. This result suggests that the technique efficiently measured alterations in renal blood oxygenation after angiotensin II-converting enzyme inhibition and that it may provide a new strategy for identifying the early stages of renal disease and perhaps new therapeutic targets.

Production rates and turnover of triiodothyronine in rat-developing cerebral cortex and cerebellum. Responses to hypothyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silva, J.E.; Matthews, P.S.

1984-09-01

Local 5'-deiodination of serum thyroxine (T4) is the main source of triiodothyronine (T3) for the brain. Since we noted in previous studies that the cerebral cortex of neonatal rats tolerated marked reductions in serum T4 without biochemical hypothyroidism, we examined the in vivo T4 and T3 metabolism in that tissue and in the cerebellum of euthyroid and hypothyroid 2-wk-old rats. We also assessed the contribution of enhanced tissue T4 to T3 conversion and decreased T3 removal from the tissues to the T3 homeostasis in hypothyroid brain. Congenital and neonatal hypothyroidism was induced by adding methimazole to the drinking water. Serum,more » cerebral cortex (Cx), cerebellum (Cm), liver (L) and kidney (R) concentrations of 125I-T4, 125I-T3(T4), and 131I-T3 were measured at various times after injecting 125I-T4 and 131I-T3. The rate of T3 removal from the tissues was measured after injecting an excess of anti-T3-antibody to rats previously injected with tracer T3. In hypothyroidism, the fractional removal rates and clearances were reduced in all tissues, in cortex and cerebellum by 70%, and in liver and kidney ranging from 30 to 50%. While greater than 80% of the 125I-T3(T4) in the brain tissues of euthyroid rats was locally produced, in hypothyroid cerebral cortex and cerebellum the integrated concentrations of 125I-T3(T4) were 2.7- and 1.5-fold greater than in euthyroid rats.« less

Qualitative and quantitative radiological analysis of non-contrast CT is a strong indicator in patients with acute pyelonephritis.

PubMed

El-Merhi, Fadi; Mohamad, May; Haydar, Ali; Naffaa, Lena; Nasr, Rami; Deeb, Ibrahim Al-Sheikh; Hamieh, Nadine; Tayara, Ziad; Saade, Charbel

2018-04-01

To evaluate the performance of non-contrast computed tomography (CT) by reporting the difference in attenuation between normal and inflamed renal parenchyma in patients clinically diagnosed with acute pyelonephritis (APN). This is a retrospective study concerned with non-contrast CT evaluation of 74 patients, admitted with a clinical diagnosis of APN and failed to respond to 48h antibiotics treatment. Mean attenuation values in Hounsfield units (HU) were measured in the upper, middle and lower segments of the inflamed and the normal kidney of the same patient. Independent t-test was performed for statistical analysis. Image evaluation included receiver operating characteristic (ROC), visual grading characteristic (VGC) and kappa analyses. The mean attenuation in the upper, middle and lower segments of the inflamed renal cortex was 32%, 25%, and 29% lower than the mean attenuation of the corresponding cortical segments of the contralateral normal kidney, respectively (p<0.01). The mean attenuation in the upper, middle, and lower segments of the inflamed renal medulla was 48%, 21%, and 30%, lower than the mean attenuation of the corresponding medullary segments of the contralateral normal kidney (p<0.02). The mean attenuation between the inflamed and non-inflamed renal cortex and medulla was 29% and 30% lower respectively (p<0.001). The AUCROC (p<0.001) analysis demonstrated significantly higher scores for pathology detection, irrespective of image quality, compared to clinical and laboratory results with an increased inter-reader agreement from poor to substantial. Non-contrast CT showed a significant decrease in the parenchymal density of the kidney affected with APN in comparison to the contralateral normal kidney of the same patient. This can be incorporated in the diagnostic criteria of APN in NCCT in the emergency setting. Copyright © 2017 Elsevier Inc. All rights reserved.

Normal sonographic anatomy of the abdomen of coatis (Nasua nasua Linnaeus 1766).

PubMed

Ribeiro, Rejane G; Costa, Ana Paula A; Bragato, Nathália; Fonseca, Angela M; Duque, Juan C M; Prado, Tales D; Silva, Andrea C R; Borges, Naida C

2013-06-23

The use of ultrasound in veterinary medicine is widespread as a diagnostic supplement in the clinical routine of small animals, but there are few reports in wild animals. The objective of this study was to describe the anatomy, topography and abdominal sonographic features of coatis. The urinary bladder wall measured 0.11 ± 0.03 cm. The symmetrical kidneys were in the left and right cranial quadrant of the abdomen and the cortical, medullary and renal pelvis regions were recognized and in all sections. The medullary rim sign was visualized in the left kidney of two coatis. The liver had homogeneous texture and was in the cranial abdomen under the rib cage. The gallbladder, rounded and filled with anechoic content was visualized in all coatis, to the right of the midline. The spleen was identified in the left cranial abdomen following the greater curvature of the stomach. The parenchyma was homogeneous and hyperechogenic compared to the liver and kidney cortex. The stomach was in the cranial abdomen, limited cranially by the liver and caudo-laterally by the spleen. The left adrenal glands of five coatis were seen in the cranial pole of the left kidney showing hypoechogenic parenchyma without distinction of cortex and medulla. The pancreas was visualized in only two coatis. The left ovary (0.92 cm x 0.56 cm) was visualized on a single coati in the caudal pole of the kidney. The uterus, right adrenal, right ovary and intestines were not visualized. Ultrasound examination of the abdomen of coatis may be accomplished by following the recommendations for dogs and cats. It is possible to evaluate the anatomical and topographical relationships of the abdominal organs together with the knowledge of the peculiarities of parenchymal echogenicity and echotexture of the viscera.

Cerebral Apolipoprotein-D Is Hypoglycosylated Compared to Peripheral Tissues and Is Variably Expressed in Mouse and Human Brain Regions.

PubMed

Li, Hongyun; Ruberu, Kalani; Karl, Tim; Garner, Brett

2016-01-01

Recent studies have shown that cerebral apoD levels increase with age and in Alzheimer's disease (AD). In addition, loss of cerebral apoD in the mouse increases sensitivity to lipid peroxidation and accelerates AD pathology. Very little data are available, however, regarding the expression of apoD protein levels in different brain regions. This is important as both brain lipid peroxidation and neurodegeneration occur in a region-specific manner. Here we addressed this using western blotting of seven different regions (olfactory bulb, hippocampus, frontal cortex, striatum, cerebellum, thalamus and brain stem) of the mouse brain. Our data indicate that compared to most brain regions, the hippocampus is deficient in apoD. In comparison to other major organs and tissues (liver, spleen, kidney, adrenal gland, heart and skeletal muscle), brain apoD was approximately 10-fold higher (corrected for total protein levels). Our analysis also revealed that brain apoD was present at a lower apparent molecular weight than tissue and plasma apoD. Utilising peptide N-glycosidase-F and neuraminidase to remove N-glycans and sialic acids, respectively, we found that N-glycan composition (but not sialylation alone) were responsible for this reduction in molecular weight. We extended the studies to an analysis of human brain regions (hippocampus, frontal cortex, temporal cortex and cerebellum) where we found that the hippocampus had the lowest levels of apoD. We also confirmed that human brain apoD was present at a lower molecular weight than in plasma. In conclusion, we demonstrate apoD protein levels are variable across different brain regions, that apoD levels are much higher in the brain compared to other tissues and organs, and that cerebral apoD has a lower molecular weight than peripheral apoD; a phenomenon that is due to the N-glycan content of the protein.

Arterially Delivered Mesenchymal Stem Cells Prevent Obstruction-Induced Renal Fibrosis

PubMed Central

Asanuma, Hiroshi; Vanderbrink, Brian A.; Campbell, Matthew T.; Hile, Karen L.; Zhang, Hongji; Meldrum, Daniel R.; Meldrum, Kirstan K.

2010-01-01

Purpose Mesenchymal stem cells (MSCs) hold promise for the treatment of renal disease. While MSCs have been shown to accelerate recovery and prevent acute renal failure in multiple disease models, the effect of MSC therapy on chronic obstruction-induced renal fibrosis has not previously been evaluated. Materials and Methods Male Sprague-Dawley rats underwent renal artery injection of vehicle or fluorescent-labeled human bone marrow-derived MSCs immediately prior to sham operation or induction of left ureteral obstruction (UUO). One or 4 weeks later, the kidneys were harvested and the renal cortex analyzed for evidence of stem cell infiltration, epithelial-mesenchymal transition (EMT) as evidenced by E-cadherin/α-smooth muscle actin (α-SMA) expression and fibroblast specific protein (FSP+) staining, renal fibrosis (collagen content, Masson’s trichrome staining), and cytokine and growth factor activity (ELISA and real time RT-PCR). Results Fluorescent-labeled MSCs were detected in the interstitium of the kidney up to 4 weeks post-obstruction. Arterially delivered MSCs significantly reduced obstruction-induced α-SMA expression, FSP+ cell accumulation, total collagen content, and tubulointerstitial fibrosis, while simultaneously preserving E-cadherin expression, suggesting that MSCs prevent obstruction-induced EMT and renal fibrosis. Exogenous MSCs reduced obstruction-induced tumor necrosis factor-α (TNF-α) levels, but did not alter transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), fibroblast growth factor (FGF), or hepatocyte growth factor (HGF) expression. Conclusions Human bone marrow-derived MSCs remain viable several weeks after delivery into the kidney and provide protection against obstruction-induced EMT and chronic renal fibrosis. While the mechanism of MSCs-induced renal protection during obstruction remains unclear, our results demonstrate that alterations in TNF-α production may be involved. PMID:20850784

Arterial flow regulator enables transplantation and growth of human fetal kidneys in rats.

PubMed

Chang, N K; Gu, J; Gu, S; Osorio, R W; Concepcion, W; Gu, E

2015-06-01

Here we introduce a novel method of transplanting human fetal kidneys into adult rats. To overcome the technical challenges of fetal-to-adult organ transplantation, we devised an arterial flow regulator (AFR), consisting of a volume adjustable saline-filled cuff, which enables low-pressure human fetal kidneys to be transplanted into high-pressure adult rat hosts. By incrementally withdrawing saline from the AFR over time, blood flow entering the human fetal kidney was gradually increased until full blood flow was restored 30 days after transplantation. Human fetal kidneys were shown to dramatically increase in size and function. Moreover, rats which had all native renal mass removed 30 days after successful transplantation of the human fetal kidney were shown to have a mean survival time of 122 days compared to 3 days for control rats that underwent bilateral nephrectomy without a prior human fetal kidney transplant. These in vivo human fetal kidney models may serve as powerful platforms for drug testing and discovery. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Aspirin, protein transacetylation and inhibition of prostaglandin synthetase in the kidney

PubMed Central

Caterson, Robyn J.; Duggin, Geoffrey G.; Horvath, John; Mohandas, Janardanan; Tiller, David

1978-01-01

1 The effect of aspirin on the kidney has been investigated in mice and rabbits. [Acetyl-14C]-aspirin was administered intraperitoneally in doses ranging from subtherapeutic to toxic. The degree of acetylation of protein was determined by the radioactivity remaining on protein precipitates of renal cortex and medulla after sequential washing designed to remove non-covalently bound material. Controls were established, by the use of [carboxyl-14C]-aspirin. 2 The acetyl-14C residue was bound to renal proteins in a linear manner in increasing amounts with increasing dosage up to 100 mg/kg. The [carboxyl-14C]-aspirin was not bound and thus the salicylate portion of the molecule was not bound covalently to the renal protein. The time course of the acetylation was rapid, consistent with the rate of aspirin absorption. The disappearance of acetylated protein was slow, with a T1/2 of 112.5 h in the renal cortex, and 129.5 h in the renal medulla. 3 Differential centrifugation, Sephadex chromatography and gel electrophoresis were carried out on tissue homogenates to determine the site of acetylation. The acetylation was greatest in the microsomal fraction, although all protein fractions showed some degree of acetylation. 4 The prostaglandin synthetase activity of a particulate preparation from rabbit kidney was determined by a spectrophotometric assay of malondialdehyde formation. Aspirin (10 mg/kg, i.v.) significantly inhibited prostaglandin synthetase in the renal cortex and medulla. 5 Aspirin and renal proteins undergo a transacetylation reaction resulting in stable acetylated protein, with acetylation being greatest in the microsomal fraction. Aspirin has been shown to inhibit prostaglandin synthetase and this could lead to functional impairment of the tissue. PMID:102389

Enhanced renal image contrast by ethanol fixation in phase-contrast X-ray computed tomography.

PubMed

Shirai, Ryota; Kunii, Takuya; Yoneyama, Akio; Ooizumi, Takahito; Maruyama, Hiroko; Lwin, Thet Thet; Hyodo, Kazuyuki; Takeda, Tohoru

2014-07-01

Phase-contrast X-ray imaging using a crystal X-ray interferometer can depict the fine structures of biological objects without the use of a contrast agent. To obtain higher image contrast, fixation techniques have been examined with 100% ethanol and the commonly used 10% formalin, since ethanol causes increased density differences against background due to its physical properties and greater dehydration of soft tissue. Histological comparison was also performed. A phase-contrast X-ray system was used, fitted with a two-crystal X-ray interferometer at 35 keV X-ray energy. Fine structures, including cortex, tubules in the medulla, and the vessels of ethanol-fixed kidney could be visualized more clearly than that of formalin-fixed tissues. In the optical microscopic images, shrinkage of soft tissue and decreased luminal space were observed in ethanol-fixed kidney; and this change was significantly shown in the cortex and outer stripe of the outer medulla. The ethanol fixation technique enhances image contrast by approximately 2.7-3.2 times in the cortex and the outer stripe of the outer medulla; the effect of shrinkage and the physical effect of ethanol cause an increment of approximately 78% and 22%, respectively. Thus, the ethanol-fixation technique enables the image contrast to be enhanced in phase-contrast X-ray imaging.

Ultrasonography of the liver and kidneys of healthy camels (Camelus dromedarius).

PubMed

Tharwat, Mohamed; Al-Sobayil, Fahd; Ali, Ahmed; Buczinski, Sébastien

2012-12-01

This study describes the ultrasonography of the liver and kidneys of healthy camels (Camelus dromedarius). Images of the liver were obtained from the 11th to 5th intercostal spaces (ICSs). The distance between the dorsal liver margin and the midline of the back was shortest (39.1 ± 7.4 cm) at the 11th ICS and increased cranially to 5th ICS. The size of the liver was largest at the 9th ICS and smallest at the 5th ICS. In 6 camels the right kidney was visualized from the 10th and 11th ICSs and upper right flank and in the 10th and 11th ICSs in the remaining 16 camels. In all camels, the left kidney was imaged from the caudal left flank. In 21 camels, the differentiation between the renal cortex and medulla was clearly visible in the ultrasonograms. Ultrasonographic description of the liver and kidneys provides a basic reference for diagnosing hepatic and renal disorders in camels.

Ultrasonography of the liver and kidneys of healthy camels (Camelus dromedarius)

PubMed Central

Tharwat, Mohamed; Al-Sobayil, Fahd; Ali, Ahmed; Buczinski, Sébastien

2012-01-01

This study describes the ultrasonography of the liver and kidneys of healthy camels (Camelus dromedarius). Images of the liver were obtained from the 11th to 5th intercostal spaces (ICSs). The distance between the dorsal liver margin and the midline of the back was shortest (39.1 ± 7.4 cm) at the 11th ICS and increased cranially to 5th ICS. The size of the liver was largest at the 9th ICS and smallest at the 5th ICS. In 6 camels the right kidney was visualized from the 10th and 11th ICSs and upper right flank and in the 10th and 11th ICSs in the remaining 16 camels. In all camels, the left kidney was imaged from the caudal left flank. In 21 camels, the differentiation between the renal cortex and medulla was clearly visible in the ultrasonograms. Ultrasonographic description of the liver and kidneys provides a basic reference for diagnosing hepatic and renal disorders in camels. PMID:23729824

Heterogeneity of renal cortical oxygenation: seeing is believing.

PubMed

Evans, Roger G; Ow, Connie P C

2018-06-01

The limited spatial and temporal resolution of available methods for quantifying renal tissue oxygen tension is a major impediment to identification of the roles of renal hypoxia in kidney diseases. Intravital phosphorescence lifetime imaging microscopy allows cellular oxygen tension in the renal cortex of live animals to be resolved to the level of individual tubular cross-sections. This paves the way for future investigations of the spatial relationships between cellular hypoxia and pathophysiological events in kidney disease. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Comparative anatomical study of the kidney position in amniotes using the origin of the renal artery as a landmark.

PubMed

Yokota, Eri; Kawashima, Tomokazu; Ohkubo, Fumie; Sasaki, Hiroshi

2005-03-01

The anatomical relationship between the kidney position and its arterial supply was investigated in 21 mammals, 1 bird, and 3 reptiles (n = 1 for each species) and in 43 human cadavers. The following observations were made. (1) Although the right kidney was located caudal to the left kidney in 29 out of 43 human cadavers (67.4%), the origin of the right renal artery from the aorta was located cranial to the origin of the left renal artery in 36 human cadavers (83.7%). Therefore, the relative positions of the kidneys do not correspond with the relative origins of the renal arteries in humans. (2) Among the mammals that were examined, the position of the kidney and the branching level of the renal artery on the right side were usually cranial to those on the left side. (3) In the bird and most reptiles that were examined, kidneys were typically located in the pelvic region and were supplied by segmental arterial branches. These results suggest that the right kidney and its arterial supply are generally located cranial to the left kidney in phylogeny of mammals. While the presence of a human accessory renal artery in 9 out of 86 sides (10.5%) and a cranial origin of the left renal artery relative to the right renal artery in 7 out of 43 cadavers (16.3%), shows some variation in the arterial supply to the kidneys, the origin of the renal arteries can generally be used as phylogenetic landmarks indicating the relative positions of the kidneys. Hence, from an ontological perspective, the human right kidney may be initially situated cranial to the left kidney during the early stages of development. Thereafter, the human right kidney may shift downwards secondary.

Effect of cephalosporins on organic ion transport in renal membrane vesicles from rat and rabbit kidney cortex.

PubMed

Williams, P D; Hitchcock, M J; Hottendorf, G H

1985-03-01

The effects of cephaloridine and cephalothin on prototypical organic anion (p-aminohippurate, PAH) and cation (N-methylnicotinamide, NMN) transport were observed in brush border and basolateral membrane vesicles prepared from rat and rabbit renal cortex. The cephalosporins interacted with both the cationic and anionic transport systems. Cephalothin inhibited PAH transport in basolateral and brush border membrane in both rats and rabbits. Cephaloridine on the other hand inhibited PAH and NMN transport across rabbit basolateral membranes while it showed a lack of interaction with transport systems in rat basolateral membranes. Conversely, cephaloridine inhibited brush border transport of PAH and NMN in the rat but not in the rabbit. These results provide indirect evidence that cephalothin may be secreted across the renal tubule cell in rats and rabbits while cephaloridine may not accumulate in the rat kidney and becomes trapped in rabbit renal tubule cells. The differences in transport effects observed may explain intra- and interspecies differences in susceptibility to cephalosporin nephrotoxicity.

Deletion of the pH sensor GPR4 decreases renal acid excretion.

PubMed

Sun, Xuming; Yang, Li V; Tiegs, Brian C; Arend, Lois J; McGraw, Dennis W; Penn, Raymond B; Petrovic, Snezana

2010-10-01

Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct.

The effect of zinc on healing of renal damage in rats

PubMed Central

Salehipour, Mehdi; Monabbati, Ahmad; Ensafdaran, Mohammad Reza; Adib, Ali; Babaei, Amir Hossein

2017-01-01

Background: Several studies have previously been performed to promote kidney healing after injuries. Objectives: The aim of this study was to investigate the effect of zinc on renal healing after traumatic injury in rats. Materials and Methods: Forty healthy female rats were selected and one of their kidneys was incised. Half of the incisions were limited only to the cortex (renal injury type I) and the other ones reached the pelvocalyceal system of the kidney (renal injury type II). All the rats in the zinc treated group (case group) received 36.3 mg zinc sulfate (contained 8.25 mg zinc) orally. After 28 days, the damaged kidneys were removed for histopathological studies. Results: In the rats with type I injury, kidney inflammation of the case group was significantly lower than that of the control group. However, the result was not significant in rats with type II injury. Tissue loss and granulation tissue formation were significantly lower in the case group than the control group in both type I and II kidney injuries. Conclusions: Overall, Zinc can contribute to better healing of the rat’s kidneys after a traumatic injury. PMID:28975095

Tissue-specific distributions of inorganic arsenic and its methylated metabolites, especially in cerebral cortex, cerebellum and hippocampus of mice after a single oral administration of arsenite.

PubMed

Li, Jinlong; Duan, Xiaoxu; Dong, Dandan; Zhang, Yang; Zhao, Lu; Li, Wei; Chen, Jinli; Sun, Guifan; Li, Bing

2017-09-01

Groundwater contaminated with inorganic arsenic (iAs) is the main source of human exposure to arsenic and generates a global health issue. In this study, the urinary excretion, as well as the time-course distributions of various arsenic species in murine tissues, especially in different brain regions were determined after a single oral administration of 2.5, 5, 10 and 20mg/kg sodium arsenite (NaAsO 2 ). Our data showed that the peak times of urinary, hepatic and nephritic total arsenic (TAs) were happened at about 1h, then TAs levels decreased gradually and almost could not be observed after 72h. On contrast, the time course of TAs in lung, urinary bladder and different brain regions exhibited an obvious process of accumulation and elimination,and the peak times were nearly at 6h to 9h. TAs levels of 10 and 20mg/kg NaAsO 2 groups were significantly higher than 2.5 and 5mg/kg groups, and the amounts of TAs in 5mg/kg groups were in the order of liver>lung>kidney>urinary bladder>hippocampus>cerebral cortex>cerebellum. In addition, iAs was the most abundant species in liver and kidney, while lung and urinary bladder accumulated the highest concentrations of dimethylated arsenicals (DMA). What's more, the distributions of arsenic species were not homogeneous among different brain regions, as DMA was the sole species in cerebral cortex and cerebellum, while extremely high concentrations and percentages of monomethylated arsenicals (MMA) were found in hippocampus. These results demonstrated that distributions of iAs and its methylated metabolites were tissue-specific and even not homogeneous among different brain regions, which must be considered as to the tissue- and region-specific toxicity of iAs exposure. Our results thus provide useful information for clarifying and reducing the uncertainty in the risk assessment for this metalloid. Copyright © 2016 Elsevier GmbH. All rights reserved.

Metabolomic Perfusate Analysis during Kidney Machine Perfusion: The Pig Provides an Appropriate Model for Human Studies

PubMed Central

Nath, Jay; Guy, Alison; Smith, Thomas B.; Cobbold, Mark; Inston, Nicholas G.; Hodson, James; Tennant, Daniel A.

2014-01-01

Introduction Hypothermic machine perfusion offers great promise in kidney transplantation and experimental studies are needed to establish the optimal conditions for this to occur. Pig kidneys are considered to be a good model for this purpose and share many properties with human organs. However it is not established whether the metabolism of pig kidneys in such hypothermic hypoxic conditions is comparable to human organs. Methods Standard criteria human (n = 12) and porcine (n = 10) kidneys underwent HMP using the LifePort Kidney Transporter 1.0 (Organ Recovery Systems) using KPS-1 solution. Perfusate was sampled at 45 minutes and 4 hours of perfusion and metabolomic analysis performed using 1-D 1H-NMR spectroscopy. Results There was no inter-species difference in the number of metabolites identified. Of the 30 metabolites analysed, 16 (53.3%) were present in comparable concentrations in the pig and human kidney perfusates. The rate of change of concentration for 3-Hydroxybutyrate was greater for human kidneys (p<0.001). For the other 29 metabolites (96.7%), there was no difference in the rate of change of concentration between pig and human samples. Conclusions Whilst there are some differences between pig and human kidneys during HMP they appear to be metabolically similar and the pig seems to be a valid model for human studies. PMID:25502759

Activities of purine converting enzymes in heart, liver and kidney mice LDLR-/- and Apo E-/.

PubMed

Rybakowska, I M; Kutryb-Zając, B; Milczarek, R; Łukasz, B; Slominska, E M; Smolenski, R T

2018-05-21

Nucleotide metabolism plays a major role in a number of vital cellular processes such as energetics. This, in turn, is important in pathologies such as atherosclerosis. Three month old atherosclerotic mice with knock outs for LDLR and apolipoprotein E (ApoE) were used for the experiments. Activities of AMP-deaminase (AMPD), ecto5'-nucleotidase (e5NT), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) were measured in heart, liver and kidney cortex and medulla by analysing conversion of substrates into products using HPLC. The activity of ecto5'-nucleotidase differ in hearts of LDLR -/- and ApoE -/- mice with no differences in ADA and AMPD activity. We noticed highest activity of e5NT in kidney medulla of the models. This model of atherosclerosis characterize with an inhibition of enzyme responsible for production of protective adenosine in heart but not in other organs and different metabolism of nucleotides in kidney medulla.

Mapping visual cortex in monkeys and humans using surface-based atlases

NASA Technical Reports Server (NTRS)

Van Essen, D. C.; Lewis, J. W.; Drury, H. A.; Hadjikhani, N.; Tootell, R. B.; Bakircioglu, M.; Miller, M. I.

2001-01-01

We have used surface-based atlases of the cerebral cortex to analyze the functional organization of visual cortex in humans and macaque monkeys. The macaque atlas contains multiple partitioning schemes for visual cortex, including a probabilistic atlas of visual areas derived from a recent architectonic study, plus summary schemes that reflect a combination of physiological and anatomical evidence. The human atlas includes a probabilistic map of eight topographically organized visual areas recently mapped using functional MRI. To facilitate comparisons between species, we used surface-based warping to bring functional and geographic landmarks on the macaque map into register with corresponding landmarks on the human map. The results suggest that extrastriate visual cortex outside the known topographically organized areas is dramatically expanded in human compared to macaque cortex, particularly in the parietal lobe.

NADPH oxidase activity and reactive oxygen species production in brain and kidney of adult male hypertensive Ren-2 transgenic rats.

PubMed

Vokurková, M; Rauchová, H; Řezáčová, L; Vaněčková, I; Zicha, J

2015-01-01

Hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play an important role in brain control of blood pressure (BP). One of the important mechanisms involved in the pathogenesis of hypertension is the elevation of reactive oxygen species (ROS) production by nicotine adenine dinucleotide phosphate (NADPH) oxidase. The aim of our present study was to investigate NADPH oxidase-mediated superoxide (O(2)(-)) production and to search for the signs of lipid peroxidation in hypothalamus and medulla oblongata as well as in renal medulla and cortex of hypertensive male rats transgenic for the murine Ren-2 renin gene (Ren-2 TGR) and their age-matched normotensive controls - Hannover Sprague Dawley rats (HanSD). We found no difference in the activity of NADPH oxidase measured as a lucigenin-mediated O(2)(-) production in the hypothalamus and medulla oblongata. However, we observed significantly elevated NADPH oxidase in both renal cortex and medulla of Ren-2 TGR compared with HanSD. Losartan (LOS) treatment (10 mg/kg body weight/day) for 2 months (Ren-2 TGR+LOS) did not change NADPH oxidase-dependent O(2)(-) production in the kidney. We detected significantly elevated indirect markers of lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS) in Ren-2 TGR, while they were significantly decreased in Ren-2 TGR+LOS. In conclusion, the present study shows increased NADPH oxidase activities in renal cortex and medulla with significantly increased TBARS in renal cortex. No significant changes of NADPH oxidase and markers of lipid peroxidation were detected in the studied brain regions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haas, M.; Forbush, B. III

(Na + K + Cl) cotransport is the major mechanism of salt transport across the apical membrane of the epithelial cells of the thick ascending limb of Henle's loop of mammalian kidney and the site of action of loop diuretics such as furosemide and bumetanide. We have identified a 150-kDa protein in membranes from dog kidney cortex that is photolabeled by a radiolabeled, benzophenone analogue of bumetanide, (/sup 3/H)4-benzoyl-5-sulfamoyl-3-(3-thenyloxy)benzoic acid ((/sup 3/H)BSTBA). Several pieces of evidence strongly suggest that this 150-kDa protein is at least part of the (Na + K + Cl) cotransport system. 1) Photoincorporation of (/sup 3/H)BSTBAmore » into this protein is completely blocked by inclusion of 10 microM unlabeled bumetanide in the photolysis medium. 2) Photoincorporation of (/sup 3/H)BSTBA into this protein shows a saturable dependence on (/sup 3/H)BSTBA concentration, with a K 1/2 (approximately 0.1 microM) very similar to that for reversible (/sup 3/H)BSTBA binding to kidney membranes. 3) Photolabeling of this protein by (/sup 3/H)BSTBA requires the simultaneous presence of Na, K, and Cl in the photolysis medium. 4) When crude membranes from dog kidney cortex are centrifuged on sucrose density gradients, saturable (/sup 3/H)bumetanide binding and photoincorporation of (/sup 3/H)BSTBA in the 150-kDa region show a very similar distribution among the 15 gradient fractions collected. (/sup 3/H)BSTBA is also photoincorporated into at least two lower molecular mass proteins, the largest of which is approximately 50 kDa.« less

Schistosoma mansoni infection causes oxidative stress and alters receptor for advanced glycation endproduct (RAGE) and tau levels in multiple organs in mice.

PubMed

de Oliveira, Ramatis Birnfeld; Senger, Mario Roberto; Vasques, Laura Milan; Gasparotto, Juciano; dos Santos, João Paulo Almeida; Pasquali, Matheus Augusto de Bittencourt; Moreira, José Claudio Fonseca; Silva, Floriano Paes; Gelain, Daniel Pens

2013-04-01

Schistosomiasis is a parasitic disease caused by trematode worms from the Schistosoma genus and is characterized by high rates of morbidity. The main organs affected in this pathology, such as liver, kidneys and spleen, are shifted to a pro-oxidant state in the course of the infection. Here, we compared oxidative stress parameters of liver, kidney and spleen with other organs affected by schistosomiasis - heart, brain cortex and lungs. The results demonstrated that mice infected with Schistosoma mansoni had altered non-enzymatic antioxidant status in lungs and brain, increased carbonyl levels in lungs, and a moderate level of oxidative stress in heart. A severe redox imbalance in liver and kidneys and decreased non-enzymatic antioxidant capacity in spleen were also observed. Superoxide dismutase and catalase activities were differently modulated in liver, kidney and heart, and we found that differences in Superoxide dismutase 2 and catalase protein content may be responsible for these differences. Lungs had decreased receptor for advanced glycation endproduct expression and the brain cortex presented altered tau expression and phosphorylation levels, suggesting important molecular changes in these tissues, as homeostasis of these proteins is widely associated with the normal function of their respective organs. We believe that these results demonstrate for the first time that changes in the redox profile and expression of tissue-specific proteins of organs such as heart, lungs and brain are observed in early stages of S. mansoni infection. Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Evolution of the cerebellar cortex: the selective expansion of prefrontal-projecting cerebellar lobules.

PubMed

Balsters, J H; Cussans, E; Diedrichsen, J; Phillips, K A; Preuss, T M; Rilling, J K; Ramnani, N

2010-02-01

It has been suggested that interconnected brain areas evolve in tandem because evolutionary pressures act on complete functional systems rather than on individual brain areas. The cerebellar cortex has reciprocal connections with both the prefrontal cortex and motor cortex, forming independent loops with each. Specifically, in capuchin monkeys cerebellar cortical lobules Crus I and Crus II connect with prefrontal cortex, whereas the primary motor cortex connects with cerebellar lobules V, VI, VIIb, and VIIIa. Comparisons of extant primate species suggest that the prefrontal cortex has expanded more than cortical motor areas in human evolution. Given the enlargement of the prefrontal cortex relative to motor cortex in humans, our hypothesis would predict corresponding volumetric increases in the parts of the cerebellum connected to the prefrontal cortex, relative to cerebellar lobules connected to the motor cortex. We tested the hypothesis by comparing the volumes of cerebellar lobules in structural MRI scans in capuchins, chimpanzees and humans. The fractions of cerebellar volume occupied by Crus I and Crus II were significantly larger in humans compared to chimpanzees and capuchins. Our results therefore support the hypothesis that in the cortico-cerebellar system, functionally related structures evolve in concert with each other. The evolutionary expansion of these prefrontal-projecting cerebellar territories might contribute to the evolution of the higher cognitive functions of humans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Renal uptake of radiolabeled octreotide in human subjects is efficiently inhibited by succinylated gelatin.

PubMed

Vegt, Erik; Wetzels, Jack F M; Russel, Frans G M; Masereeuw, Rosalinde; Boerman, Otto C; van Eerd, Juliette E; Corstens, Frans H M; Oyen, Wim J G

2006-03-01

Peptide receptor-mediated radiotherapy of neuroendocrine and other somatostatin receptor-positive tumors with radiolabeled somatostatin analogs has been applied in several experimental settings. The kidneys are the organs responsible for dose-limiting toxicity attributable to the retention of radiolabeled octreotide in the renal cortex, leading to a relatively high radiation dose that may result in irreversible loss of kidney function. The administration of basic amino acids reduces renal uptake but does have significant side effects. We observed that gelatin-based plasma expanders induced tubular low-molecular-weight proteinuria in healthy volunteers, suggesting that components in these solutions can interfere with the tubular reabsorption of proteins and peptides. Here, we studied the effects of infusion of low doses of the plasma expander succinylated gelatin (GELO) on the renal uptake of 111In-labeled octreotide (111In-OCT). Five healthy volunteers were given 111In-OCT, first in combination with normal saline and 2 wk later in combination with GELO. Scintigraphic images of the kidneys as well as blood and urine samples were analyzed. To exclude a nonspecific hemodynamic effect of the plasma expander, the procedure was repeated with 5 other volunteers who received the carbohydrate-based plasma expander hydroxyethyl starch (HES). Low doses of GELO were able to effectively reduce the kidney retention of 111In-OCT. The renal radiation dose was significantly reduced by 45% +/- 10% (mean +/- SD) (P = 0.006), whereas HES showed no significant effect (0% +/- 12%). The infusion of GELO did not cause any side effects. GELO effectively reduces the renal uptake of 111In-OCT. In contrast to currently used mixtures of amino acids, GELO does not cause any side effects.

Localization of a renal sodium-phosphate cotransporter gene to human chromosome 5q35

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kos, C.H.; Tenenhouse, H.S.; Tihy, F.

1994-01-01

Several Mendelian disorders of renal phosphate reabsorption, associated with hypophosphatemia and bone disease, have been described. These include X-linked hypophosphatemia (XLH), hereditary hypophosphatemic rickets with hypercalciuria, hypophosphatemic bone disease, and autosomal dominant and autosomal recessive hypophosphatemic rickets. The underlying mechanisms for renal phosphate wasting in these disorders remain unknown. The proximal tubule is the major site of renal phosphate reabsorption. Thus, mutations in genes that participate in the transepithelial transport of phosphate in this segment of the nephron may be responsible for these disorders. Recently, a cDNA encoding a renal proximal tubular, brush-border membrane Na[sup +]-phosphate cotransporter (NaP[sub i]-3) wasmore » cloned from human kidney cortex. As a first step in establishing whether mutations in the NaP[sub i]-3 gene are the cause of inherited disorders in phosphate homeostasis, the authors sought to determine its chromosomal localization. 9 refs., 1 fig.« less

Comparative study of allogenic and xenogeneic mesenchymal stem cells on cisplatin-induced acute kidney injury in Sprague-Dawley rats.

PubMed

Ashour, Rehab H; Saad, Mohamed-Ahdy; Sobh, Mohamed-Ahmed; Al-Husseiny, Fatma; Abouelkheir, Mohamed; Awad, Amal; Elghannam, Doaa; Abdel-Ghaffar, Hassan; Sobh, Mohamed

2016-09-01

The paracrine and regenerative activities of mesenchymal stem cells (MSCs) may vary with different stem cell sources. The aim of the present study is to compare the effects of MSCs from different sources on acute kidney injury (AKI) induced by cisplatin and their influence on renal regeneration. A single intraperitoneal injection of cisplatin (5 mg/kg) was used to induce AKI in 120 Sprague-Dawley rats. Rats were treated with either rat bone marrow stem cells (rBMSCs), human adipose tissue-derived stem cells (hADSCs), or human amniotic fluid-derived stem cells (hAFSCs). 5 × 10(6) MSCs of different sources were administered through rat tail vein in a single dose, 24 hours after cisplatin injection. Within each group, rats were sacrificed at the 4th, 7th, 11th, and 30th day after cisplatin injection. Serum creatinine, BUN, and renal tissue oxidative stress parameters were measured. Renal tissue was scored histopathologically for evidence of injury, regeneration, and chronicity. Immunohistochemistry was also done using Ki67 for renal proliferative activity evaluation. MSCs of the three sources were able to ameliorate cisplatin-induced renal function deterioration and tissue damage. The rat BMSCs-treated group had the lowest serum creatinine by day 30 (0.52 ± 0.06) compared to hADSCs and hAFSCs. All MSC-treated groups had nearly equal antioxidant activity as indicated by the decreased renal tissue malondialdehyde (MDA) and increased reduced glutathione (GSH) level and superoxide dismutase (SOD) activity at different time intervals. Additionally, all MSCs improved injury and regenerative scores. Rat BMSCs had the highest count and earliest proliferative activity in the renal cortex by day 7 as identified by Ki67; while, hAFSCs seem to have the greatest improvement in the regenerative and proliferative activities with a higher count of renal cortex Ki67-positive cells at day 11 and with the least necrotic lesions. Rat BMSCs, hADSCs, and hAFSCs, in early single IV dose, had a renoprotective effect against cisplatin-induced AKI, and were able to reduce oxidative stress markers. Rat BMSCs had the earliest proliferative activity by day 7; however, hAFSCs seemed to have the greatest improvement in the regenerative activities. Human ADSCs were the least effective in the terms of proliferative and regenerative activities.

Perinatal Diagnosis, Management, and Follow-up of Cystic Renal Diseases: A Clinical Practice Recommendation With Systematic Literature Reviews.

PubMed

Gimpel, Charlotte; Avni, Fred E; Bergmann, Carsten; Cetiner, Metin; Habbig, Sandra; Haffner, Dieter; König, Jens; Konrad, Martin; Liebau, Max C; Pape, Lars; Rellensmann, Georg; Titieni, Andrea; von Kaisenberg, Constantin; Weber, Stefanie; Winyard, Paul J D; Schaefer, Franz

2018-01-01

Prenatal and neonatal cystic kidney diseases are a group of rare disorders manifesting as single, multiple unilateral, or bilateral cysts or with increased echogenicity of the renal cortex without macroscopic cysts. They may be accompanied by grossly enlarged kidneys, renal oligohydramnios, pulmonary hypoplasia, extrarenal abnormalities, and neonatal kidney failure. The prognosis is extremely variable from trivial to very severe or even uniformly fatal, which poses significant challenges to prenatal counseling and management. To provide a clinical practice recommendation for fetal medicine specialists, obstetricians, neonatologists, pediatric nephrologists, pediatricians, and human geneticists by aggregating current evidence and consensus expert opinion on current management of cystic nephropathies before and after birth. After 8 systematic literature reviews on clinically relevant questions were prepared (including 90 studies up to mid-2016), recommendations were formulated and formally graded at a consensus meeting that included experts from all relevant specialties. After further discussion, the final version was voted on by all members using the Delphi method. The recommendations were reviewed and endorsed by the working groups on inherited renal disorders of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) and European Society for Paediatric Nephrology (ESPN); the German Society of Obstetrics and Gynecology (DGGG), German Society of Perinatal Medicine (DGPM), and German Society of Ultrasound in Medicine (DEGUM); and the alliance of patient organizations, PKD International. The group makes a number of recommendations on prenatal and postnatal imaging by ultrasound and magnetic resonance imaging, genetic testing, prenatal counseling, in utero therapeutic interventions, and postnatal management of prenatal and neonatal cystic kidney diseases, including provision of renal replacement therapy in neonates. In addition to detailed knowledge about possible etiologies and their prognosis, physicians need to be aware of recent improvements and remaining challenges of childhood chronic kidney disease, neonatal renal replacement therapy, and intensive pulmonary care to manage these cases and to empower parents for informed decision making.

Monitoring of renal ischemia reperfusion injury in rabbits by ultrasonic contrast and its relationship with expression of VEGF in renal tissue.

PubMed

Hao, Peng

2016-02-01

To evaluate the renal ischemia reperfusion injury (IRI) in rabbits using the ultrasonic contrast technique and discuss the clinical value of ultrasonic contrast technique in the diagnosis of renal IRI by comparing the time-intensity curve of renal cortex and the expression of vascular endothelial growth factor (VEGF) of renal tissue. Twenty 3-month-old New Zealand rabbits were randomly divided into 4 groups, namely Ctrl group, IRI-12 h, IRI-24 h and IRI-48 h groups. The two dimensional gray-scale ultrasonography was employed to determine and mark the position of rabbit kidney. Rabbits were given the intraperitoneal anesthesia with 20% urethane with the dosage of 5 mL/kg. The aseptic operation was performed after the local skin disinfection in the area of both kidneys. The right kidney of animals in the control group was excised without any treatment for the left kidney. After excising the right kidney of animals in groups of IRI-12 h, IRI-24 h and IRI-48 h, the aneurysm clip was used to clip the renal pedicle vessel of left kidney, in order to simulate the ischemia. Because of the tissue ischemia, it could be seen that the color of kidney was changed from bright red to dark red, which indicated the successful modeling of ischemia. The aneurysm clip was released after one hour of maintaining the ischemia. Then the kidney turned out to be bright red from dark red, which indicated that the reperfusion was completed. Taking this moment as the time of ischemia reperfusion, the wound was stitched up. A total of 12, 24 and 36 h after the operation, the two-dimensional and color Doppler flow imaging and ultrasonic contrast were employed for the examination. The dynamic changes of ultrasonic contrast were recorded. The quantitative analysis software (QontraXt) was adopted to analyze the time-intensity curve of echo at different positions of renal cortex. After the ultrasonic contrast testing, rabbits were put to death. The renal cortex tissue was isolated and the tissue RNA and total protein were extracted respectively. Real-time PCR and western blotting were used to detect the VEGF and the Pearson product moment correlation coefficient was used to measure the linear relationship between these two variables. The ultrasonic contrast could clearly reflect the process of IRI. The results of testing at mRNA and protein level indicated that the expression of VEGF in IRI groups was significantly increased (P < 0.05) and the expression of VEGF was also increased by the time of reperfusion. There is the certain correlation between the expression of VEGF and process of IRI. The correlation coefficient between the ultrasonic contrast parameters of AT and TTP and the relative expression of VEGF is over 0.9, which indicates the relatively high correlation. But there is no significant difference in the change of perfusion peak intensity between groups, which has no correlation with the expression of VEGF. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Managing competing goals - a key role for the frontopolar cortex.

PubMed

Mansouri, Farshad Alizadeh; Koechlin, Etienne; Rosa, Marcello G P; Buckley, Mark J

2017-11-01

Humans are set apart from other animals by many elements of advanced cognition and behaviour, including language, judgement and reasoning. What is special about the human brain that gives rise to these abilities? Could the foremost part of the prefrontal cortex (the frontopolar cortex), which has become considerably enlarged in humans during evolution compared with other animals, be important in this regard, especially as, in primates, it contains a unique cytoarchitectural field, area 10? The first studies of the function of the frontopolar cortex in monkeys have now provided critical new insights about its precise role in monitoring the significance of current and alternative goals. In human evolution, the frontopolar cortex may have acquired a further role in enabling the monitoring of the significance of multiple goals in parallel, as well as switching between them. Here, we argue that many other forms of uniquely human behaviour may benefit from this cognitive ability mediated by the frontopolar cortex.

9-Hydroxyprostaglandin dehydrogenase activity in the adult rat kidney. Regional distribution and sub-fractionation.

PubMed

Asciak, C P; Domazet, Z

1975-02-20

1. Catabolism of prostaglandin F2alpha in the adult rat kidney takes place by the following sequence of enzymatic steps: (1) 15-hydroxyprostaglandin dehydrogenase; (2) prostaglandin delta13-reductase; and (3) 9-hydroxyprostaglandin dehydrogenase. 2. 9-Hydroxyprostaglandin dehydrogenase activity was highest in the cortex with lesser amounts in the medulla and negligible activity detected in the papilla. A similar distribution was observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 3. Most of the 9-hydroxyprostaglandin dehydrogenase activity in the homogenate was found in the high-speed supernatant as also observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 4. These observations indicate that the rat kidney contains an abundance of prostaglandin-catabolising enzymes which favour formation of metabolites of the E-type.

Cadmium, mercury, and lead in kidney cortex of living kidney donors: Impact of different exposure sources,

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barregard, Lars, E-mail: lars.barregard@amm.gu.se; Fabricius-Lagging, Elisabeth; Lundh, Thomas

Background: Most current knowledge on kidney concentrations of nephrotoxic metals like cadmium (Cd), mercury (Hg), or lead (Pb) comes from autopsy studies. Assessment of metal concentrations in kidney biopsies from living subjects can be combined with information about exposure sources like smoking, diet, and occupation supplied by the biopsied subjects themselves. Objectives: To determine kidney concentrations of Cd, Hg, and Pb in living kidney donors, and assess associations with common exposure sources and background factors. Methods: Metal concentrations were determined in 109 living kidney donors aged 24-70 years (median 51), using inductively coupled plasma-mass spectrometry (Cd and Pb) and coldmore » vapor atomic fluorescence spectrometry (Hg). Smoking habits, occupation, dental amalgam, fish consumption, and iron stores were evaluated. Results: The median kidney concentrations were 12.9 {mu}g/g (wet weight) for cadmium, 0.21 {mu}g/g for mercury, and 0.08 {mu}g/g for lead. Kidney Cd increased by 3.9 {mu}g/g for a 10 year increase in age, and by 3.7 {mu}g/g for an extra 10 pack-years of smoking. Levels in non-smokers were similar to those found in the 1970s. Low iron stores (low serum ferritin) in women increased kidney Cd by 4.5 {mu}g/g. Kidney Hg increased by 6% for every additional amalgam surface, but was not associated with fish consumption. Lead was unaffected by the background factors surveyed. Conclusions: In Sweden, kidney Cd levels have decreased due to less smoking, while the impact of diet seems unchanged. Dental amalgam is the main determinant of kidney Hg. Kidney Pb levels are very low due to decreased exposure.« less

Computed tomography of the liver and kidneys in glycogen storage disease.

PubMed

Doppman, J L; Cornblath, M; Dwyer, A J; Adams, A J; Girton, M E; Sidbury, J

1982-02-01

Glycogen, in concentrations encountered in von Gierke's disease, has computed tomography (CT) attenuation coefficients in the 50 to 70 Hounsfield unit (HU: 1,000 scale) range and accounts for the increased density of the liver. However, in eight patients with Type I glycogen storage disease, simultaneous hepatic infiltration with fat and glycogen led to a range of liver CT densities from 13 to 80 HU. Fatty infiltration may facilitate the demonstration of hepatic tumors in older patients with this disease. Half the patients showed increased attenuation coefficients of the renal cortex, indicating glycogen deposition in the kidneys.

Suramin protects from cisplatin-induced acute kidney injury

PubMed Central

Dupre, Tess V.; Doll, Mark A.; Shah, Parag P.; Sharp, Cierra N.; Kiefer, Alex; Scherzer, Michael T.; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E.; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G.; Beverly, Levi J.

2015-01-01

Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer. PMID:26661653

The State of the Human Proteome in 2013 as viewed through PeptideAtlas: Comparing the Kidney, Urine, and Plasma Proteomes for the Biology and Disease-driven Human Proteome Project

PubMed Central

Farrah, Terry; Deutsch, Eric W.; Omenn, Gilbert S.; Sun, Zhi; Watts, Julian D.; Yamamoto, Tadashi; Shteynberg, David; Harris, Micheleen M.; Moritz, Robert L.

2014-01-01

The kidney, urine, and plasma proteomes are intimately related: proteins and metabolic waste products are filtered from the plasma by the kidney and excreted via the urine, while kidney proteins may be secreted into the circulation or released into the urine. Shotgun proteomics datasets derived from human kidney, urine, and plasma samples were collated and processed using a uniform software pipeline, and relative protein abundances were estimated by spectral counting. The resulting PeptideAtlas builds yielded 4005, 2491, and 3553 nonredundant proteins at 1% FDR for the kidney, urine, and plasma proteomes, respectively—for kidney and plasma, the largest high-confidence protein sets to date. The same pipeline applied to all available human data yielded a 2013 Human PeptideAtlas build containing 12,644 nonredundant proteins and at least one peptide for each of ~14,000 Swiss-Prot entries, an increase over 2012 of ~7.5% of the predicted human proteome. We demonstrate that abundances are correlated between plasma and urine, examine the most abundant urine proteins not derived from either plasma or kidney, and consider the biomarker potential of proteins associated with renal decline. This analysis forms part of the Biology and Disease-driven Human Proteome Project (B/D-HPP) and a contribution to the Chromosome-centric Human Proteome Project (C-HPP) special issue. PMID:24261998

Reduced Sulfation of Chondroitin Sulfate but Not Heparan Sulfate in Kidneys of Diabetic db/db Mice

PubMed Central

Reine, Trine M.; Grøndahl, Frøy; Jenssen, Trond G.; Hadler-Olsen, Elin; Prydz, Kristian

2013-01-01

Heparan sulfate proteoglycans are hypothesized to contribute to the filtration barrier in kidney glomeruli and the glycocalyx of endothelial cells. To investigate potential changes in proteoglycans in diabetic kidney, we isolated glycosaminoglycans from kidney cortex from healthy db/+ and diabetic db/db mice. Disaccharide analysis of chondroitin sulfate revealed a significant decrease in the 4-O-sulfated disaccharides (D0a4) from 65% to 40%, whereas 6-O-sulfated disaccharides (D0a6) were reduced from 11% to 6%, with a corresponding increase in unsulfated disaccharides. In contrast, no structural differences were observed in heparan sulfate. Furthermore, no difference was found in the molar amount of glycosaminoglycans, or in the ratio of hyaluronan/heparan sulfate/chondroitin sulfate. Immunohistochemical staining for the heparan sulfate proteoglycan perlecan was similar in both types of material but reduced staining of 4-O-sulfated chondroitin and dermatan was observed in kidney sections from diabetic mice. In support of this, using qRT-PCR, a 53.5% decrease in the expression level of Chst-11 (chondroitin 4-O sulfotransferase) was demonstrated in diabetic kidney. These results suggest that changes in the sulfation of chondroitin need to be addressed in future studies on proteoglycans and kidney function in diabetes. PMID:23757342

Reduced sulfation of chondroitin sulfate but not heparan sulfate in kidneys of diabetic db/db mice.

PubMed

Reine, Trine M; Grøndahl, Frøy; Jenssen, Trond G; Hadler-Olsen, Elin; Prydz, Kristian; Kolset, Svein O

2013-08-01

Heparan sulfate proteoglycans are hypothesized to contribute to the filtration barrier in kidney glomeruli and the glycocalyx of endothelial cells. To investigate potential changes in proteoglycans in diabetic kidney, we isolated glycosaminoglycans from kidney cortex from healthy db/+ and diabetic db/db mice. Disaccharide analysis of chondroitin sulfate revealed a significant decrease in the 4-O-sulfated disaccharides (D0a4) from 65% to 40%, whereas 6-O-sulfated disaccharides (D0a6) were reduced from 11% to 6%, with a corresponding increase in unsulfated disaccharides. In contrast, no structural differences were observed in heparan sulfate. Furthermore, no difference was found in the molar amount of glycosaminoglycans, or in the ratio of hyaluronan/heparan sulfate/chondroitin sulfate. Immunohistochemical staining for the heparan sulfate proteoglycan perlecan was similar in both types of material but reduced staining of 4-O-sulfated chondroitin and dermatan was observed in kidney sections from diabetic mice. In support of this, using qRT-PCR, a 53.5% decrease in the expression level of Chst-11 (chondroitin 4-O sulfotransferase) was demonstrated in diabetic kidney. These results suggest that changes in the sulfation of chondroitin need to be addressed in future studies on proteoglycans and kidney function in diabetes.

Regional cyst concentration as a prognostic biomarker for polycystic kidney disease

NASA Astrophysics Data System (ADS)

Warner, Joshua D.; Irazabal, Maria V.; Torres, Vicente E.; King, Bernard F.; Erickson, Bradley J.

2014-03-01

Polycystic kidney disease (PKD) is a major cause of renal failure. Despite recent advances in understanding the biochemistry and genetics of PKD, the functional mechanisms underpinning the declines in renal function observed in the disorder are not well established. No studies investigating the distribution of cysts within polycystic kidneys exist. This work introduces regional cyst concentration as a new biomarker for evaluation of patients suffering from PKD. We derive a method to define central and peripheral regions of the kidney, approximating the anatomical division between cortex and medulla, and apply it to two cohorts of ten patients with early/mild or late/severe disease. Our results from the late/severe cohort show peripheral cyst concentration correlates with the current standard PKD biomarker, total kidney volume (TKV), signi cantly better than central cyst concentration (p < 0.05). We also find that cyst concentration was globally increased in the late/severe cohort (p << 0.01) compared to the early/mild cohort, for both central and peripheral regions. These findings show cysts in PKD are not distributed homogeneously throughout the renal tissues.

Normal sonographic anatomy of the abdomen of coatis (Nasua nasua Linnaeus 1766)

PubMed Central

2013-01-01

Background The use of ultrasound in veterinary medicine is widespread as a diagnostic supplement in the clinical routine of small animals, but there are few reports in wild animals. The objective of this study was to describe the anatomy, topography and abdominal sonographic features of coatis. Results The urinary bladder wall measured 0.11 ± 0.03 cm. The symmetrical kidneys were in the left and right cranial quadrant of the abdomen and the cortical, medullary and renal pelvis regions were recognized and in all sections. The medullary rim sign was visualized in the left kidney of two coatis. The liver had homogeneous texture and was in the cranial abdomen under the rib cage. The gallbladder, rounded and filled with anechoic content was visualized in all coatis, to the right of the midline. The spleen was identified in the left cranial abdomen following the greater curvature of the stomach. The parenchyma was homogeneous and hyperechogenic compared to the liver and kidney cortex. The stomach was in the cranial abdomen, limited cranially by the liver and caudo-laterally by the spleen. The left adrenal glands of five coatis were seen in the cranial pole of the left kidney showing hypoechogenic parenchyma without distinction of cortex and medulla. The pancreas was visualized in only two coatis. The left ovary (0.92 cm x 0.56 cm) was visualized on a single coati in the caudal pole of the kidney. The uterus, right adrenal, right ovary and intestines were not visualized. Conclusions Ultrasound examination of the abdomen of coatis may be accomplished by following the recommendations for dogs and cats. It is possible to evaluate the anatomical and topographical relationships of the abdominal organs together with the knowledge of the peculiarities of parenchymal echogenicity and echotexture of the viscera. PMID:23800301

Transcutaneous Electrical Nerve Stimulation Regulates Organ Blood Flow and Apoptosis during Controlled Hypotension in Dogs

PubMed Central

Zhang, Lele; Shao, Xiaomei; Zhou, Chuanlong; Guo, Xiaoqing; Jin, Ling; Lian, Linli; Yu, Xiaojing; Dong, Zhenhua; Mo, Yadi; Fang, Jianqiao

2014-01-01

Transcutaneous electrical nerve stimulation (TENS) is commonly used in clinical practice for alleviating pains and physiological disorders. It has been reported that TENS could counteract the ischemic injury happened in some vital organs. To determine the protective effect of TENS on internal organs during CH in dogs, target hypotension was maintained for 60 min at 50% of the baseline mean arterial pressure (MAP). The perfusion to the brain, liver, stomach, and kidney was recorded and apoptosis within these organs was observed. Results showed that when arriving at the target MAP, and during the maintaining stage for 10 min, perfusion to the stomach and liver in the CH+TENS group was much higher than in the CH group (P<0.05). Perfusion to the cerebral cortex greatly declined in both the controlled pressure groups when compared with the general anesthesia (GA) group (P<0.05). After withdrawing CH, the hepatic blood flow in both the CH and CH+TENS groups, and the gastric and cerebral cortical blood flow in the CH+TENS group, were rapidly increased. By the end of MAP restoration, gastric blood flow in the CH group was still low. At 72 h after applying CH, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in stomach and kidney tissue from the CH group were significantly increased compared with those in the GA group (P<0.05). There was no significant difference in TUNEL-positive cells in the liver and hippocampus among the three groups. Our results demonstrated that CH with a 50% MAP level could cause lower perfusion to the liver, stomach, cerebral cortex, and kidney, with apoptosis subsequently occurring in the stomach and kidney. TENS combined GA is able to improve the blood flow to the liver, stomach, and reduce the apoptosis in the stomach and kidney. PMID:24732970

Hyperactivation of Akt/mTOR and deficiency in tuberin increased the oxidative DNA damage in kidney cancer patients with diabetes

PubMed Central

Habib, Samy L.; Liang, Sitai

2014-01-01

Recent study from our laboratory showed that patients with diabetes are at a higher risk of developing kidney cancer. In the current study, we have explored one of the mechanisms by which diabetes accelerates tumorigenesis in the kidney. Kidney cancer tissue from patients with diabetes showed a higher activity of Akt and decreased in total protein of tuberin compared to kidney cancer patient without diabetes or diabetes alone. In addition, a significant increase in phospho-Akt/tuberin expression was associated with an increase in Ki67 expression and activation of mTOR in kidney tumor with or without diabetes compared to diabetes alone. In addition, decrease in tuberin expression resulted in a significant decrease in protein expression of OGG1 and increased in oxidative DNA damage, 8-oxodG in kidney tissues from patients with cancer or cancer+diabetes. Importantly, these data showed that the majority of the staining of Akt/tuberin/p70S6K phosphorylation was more prominently in the tubular cells. In addition, accumulation of oxidative DNA damage is localized only in the nucleus of tubular cells within the cortex region. These data suggest that Akt/tuberin/mTOR pathway plays an important role in the regulation DNA damage and repair pathways that may predispose diabetic kidneys to pathogenesis of renal cell carcinoma. PMID:24797175

Nebivolol prevents ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat kidney by regulating NADPH oxidase activation and expression.

PubMed

do Vale, Gabriel T; Gonzaga, Natália A; Simplicio, Janaina A; Tirapelli, Carlos R

2017-03-15

We studied whether the β 1 -adrenergic antagonist nebivolol would prevent ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat renal cortex. Male Wistar rats were treated with ethanol (20% v/v) for 2 weeks. Nebivolol (10mg/kg/day; p.o. gavage) prevented both the increase in superoxide anion (O 2 - ) generation and thiobarbituric acid reactive substances (TBARS) concentration induced by ethanol in the renal cortex. Ethanol decreased nitrate/nitrite (NOx) concentration in the renal cortex, and nebivolol prevented this response. Nebivolol did not affect the reduction of hydrogen peroxide (H 2 O 2 ) concentration induced by ethanol. Nebivolol prevented the ethanol-induced increase of catalase (CAT) activity. Both SOD activity and the levels of reduced glutathione (GSH) were not affected by treatment with nebivolol or ethanol. Neither ethanol nor nebivolol affected the expression of Nox1, Nox4, eNOS, nNOS, CAT, Nox organizer 1 (Noxo1), c-Src, p47 phox or superoxide dismutase (SOD) isoforms in the renal cortex. On the other hand, treatment with ethanol increased Nox2 expression, and nebivolol prevented this response. Finally, nebivolol reduced the expression of protein kinase (PK) Cδ and Rac1. The major finding of our study is that nebivolol prevented ethanol-induced reactive oxygen species generation and lipoperoxidation in the kidney by a mechanism that involves reduction on the expression of Nox2, a catalytic subunit of NADPH oxidase. Additionally, we demonstrated that nebivolol reduces NADPH oxidase-derived reactive oxygen species by decreasing the expression of PKCδ and Rac1, which are important activators of NADPH oxidase. Copyright © 2017 Elsevier B.V. All rights reserved.

The assessment of renal cortex and parenchymal volume using automated CT volumetry for predicting renal function after donor nephrectomy.

PubMed

Mitsui, Yosuke; Sadahira, Takuya; Araki, Motoo; Wada, Koichiro; Tanimoto, Ryuta; Ariyoshi, Yuichi; Kobayashi, Yasuyuki; Watanabe, Masami; Watanabe, Toyohiko; Nasu, Yasutomo

2018-04-01

Contrast-enhanced CT is necessary before donor nephrectomy and is usually combined with a Tc-99m-mercapto-acetyltriglycine (MAG3) scan to check split renal function (SRF). However, all transplant programs do not use MAG3 because of its high cost and exposure to radiation. We examined whether CT volumetry of the kidney can be a new tool for evaluating SRF. Sixty-three patients underwent live donor nephrectomy. Patients without a 1.0 mm slice CT or follow-up for <12 months were excluded leaving 34 patients' data being analyzed. SRF was measured by MAG3. Split renal volume (SRV) was calculated automatically using volume analyzer software. The correlation between SRF and SRV was examined. The association between the donor's postoperative estimated glomerular filtration rate (eGFR) and predicted eGFR calculated by MAG3 or CT volumetry was analyzed at 1, 3, and 12 months post nephrectomy. Strong correlations were observed preoperatively in a Bland-Altman plot between SRF measured by MAG3 and either CT cortex or parenchymal volumetry. In addition, eGFR after donation correlated with SRF measured by MAG3 or CT volumetry. The correlation coefficients (R) for eGFR Mag3 split were 0.755, 0.615, and 0.763 at 1, 3 and 12 months, respectively. The corresponding R values for cortex volume split were 0.679, 0.638, and 0.747. Those for parenchymal volume split were 0.806, 0.592, and 0.764. Measuring kidney by CT volumetry is a cost-effective alternative to MAG3 for evaluating SRF and predicting postoperative donor renal function. Both cortex and parenchymal volumetry were similarly effective.

(Re)Building a Kidney

PubMed Central

Carroll, Thomas J.; Cleaver, Ondine; Gossett, Daniel R.; Hoshizaki, Deborah K.; Hubbell, Jeffrey A.; Humphreys, Benjamin D.; Jain, Sanjay; Jensen, Jan; Kaplan, David L.; Kesselman, Carl; Ketchum, Christian J.; Little, Melissa H.; McMahon, Andrew P.; Shankland, Stuart J.; Spence, Jason R.; Valerius, M. Todd; Wertheim, Jason A.; Wessely, Oliver; Zheng, Ying; Drummond, Iain A.

2017-01-01

(Re)Building a Kidney is a National Institute of Diabetes and Digestive and Kidney Diseases-led consortium to optimize approaches for the isolation, expansion, and differentiation of appropriate kidney cell types and the integration of these cells into complex structures that replicate human kidney function. The ultimate goals of the consortium are two-fold: to develop and implement strategies for in vitro engineering of replacement kidney tissue, and to devise strategies to stimulate regeneration of nephrons in situ to restore failing kidney function. Projects within the consortium will answer fundamental questions regarding human gene expression in the developing kidney, essential signaling crosstalk between distinct cell types of the developing kidney, how to derive the many cell types of the kidney through directed differentiation of human pluripotent stem cells, which bioengineering or scaffolding strategies have the most potential for kidney tissue formation, and basic parameters of the regenerative response to injury. As these projects progress, the consortium will incorporate systematic investigations in physiologic function of in vitro and in vivo differentiated kidney tissue, strategies for engraftment in experimental animals, and development of therapeutic approaches to activate innate reparative responses. PMID:28096308

Reconstruction and Analysis of Human Kidney-Specific Metabolic Network Based on Omics Data

PubMed Central

Zhang, Ai-Di; Dai, Shao-Xing; Huang, Jing-Fei

2013-01-01

With the advent of the high-throughput data production, recent studies of tissue-specific metabolic networks have largely advanced our understanding of the metabolic basis of various physiological and pathological processes. However, for kidney, which plays an essential role in the body, the available kidney-specific model remains incomplete. This paper reports the reconstruction and characterization of the human kidney metabolic network based on transcriptome and proteome data. In silico simulations revealed that house-keeping genes were more essential than kidney-specific genes in maintaining kidney metabolism. Importantly, a total of 267 potential metabolic biomarkers for kidney-related diseases were successfully explored using this model. Furthermore, we found that the discrepancies in metabolic processes of different tissues are directly corresponding to tissue's functions. Finally, the phenotypes of the differentially expressed genes in diabetic kidney disease were characterized, suggesting that these genes may affect disease development through altering kidney metabolism. Thus, the human kidney-specific model constructed in this study may provide valuable information for the metabolism of kidney and offer excellent insights into complex kidney diseases. PMID:24222897

[Review for treatment effect and signaling pathway regulation of kidney-tonifying traditional Chinese medicine on osteoporosis].

PubMed

Xiao, Ya-Ping; Zeng, Jie; Jiao, Lin-Na; Xu, Xiao-Yu

2018-01-01

The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/ β -catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus and Psoraleae Fructus up-regulated the expression of key proteins and genes of BMP-Smads and Wnt/ β -catenin signaling pathways to promote bone formation. Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix inhibited the bone resorption by mediating the OPG/RANKL/RANK signaling pathway. ②Kidney-tonifying traditional Chinese medicine prevented and treated osteoporosis through a variety of ways: icariin in Epimedii Folium, naringin in Drynariae Rhizoma, osthole in Cnidii Fructus and psoralen in Psoraleae Fructus can regulate BMP-Smads, Wnt/ β -catenin signaling pathway to promote bone formation, but also activate OPG/RANKL/RANK, CTSK and other signaling pathways to inhibit bone resorption. ③The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification. Copyright© by the Chinese Pharmaceutical Association.

Analysis of spatiotemporal metabolomic dynamics for sensitively monitoring biological alterations in cisplatin-induced acute kidney injury.

PubMed

Irie, Miho; Hayakawa, Eisuke; Fujimura, Yoshinori; Honda, Youhei; Setoyama, Daiki; Wariishi, Hiroyuki; Hyodo, Fuminori; Miura, Daisuke

2018-01-29

Clinical application of the major anticancer drug, cisplatin, is limited by severe side effects, especially acute kidney injury (AKI) caused by nephrotoxicity. The detailed metabolic mechanism is still largely unknown. Here, we used an integrated technique combining mass spectrometry imaging (MSI) and liquid chromatography-mass spectrometry (LC-MS) to visualize the diverse spatiotemporal metabolic dynamics in the mouse kidney after cisplatin dosing. Biological responses to cisplatin was more sensitively detected within 24 h as a metabolic alteration, which is much earlier than possible with the conventional clinical chemistry method of blood urea nitrogen (BUN) measurement. Region-specific changes (e.g., medulla and cortex) in metabolites related to DNA damage and energy generation were observed over the 72-h exposure period. Therefore, this metabolomics approach may become a novel strategy for elucidating early renal responses to cisplatin, prior to the detection of kidney damage evaluated by conventional method. Copyright © 2018. Published by Elsevier Inc.

[Comparative studies on the toxicity of various dielectrics--petroleum derivatives used in the electroerosion technic. V. Functional, morphological and cytoenzymatic changes in the kidneys of rats chronically exposed to petroleum hydrocarbons].

PubMed

Starek, A; Kamiński, M

1982-01-01

The rats exposed for 14 weeks to odourless kerosene mists (concentration of 75 and 300 mg/m3) had their urinary chemical and morphotic composition determined. In addition, morphological and cytoenzymatic examinations of kidneys were carried out. The findings were: increased pH and protein concentration and single erythrocytes in urine and also: passive congestion of renal cortex and medulla, infiltrates composed of granulocytes and eosinophils and albuminous casts in renal tubules. Decreased activity of succinate dehydrogenase, glucoso-6-phosphatase, Mg++ stimulated adenosinotriphosphatase and increased activity of acid phosphatase were found. Those changes were localized in cortical part of the kidney especially in the main tubules epithelial cells. The observed functional, morphological and cytoenzymatic changes depended on the magnitude of exposure. The obtained results confirm that kerosene hydrocarbons may exhibit toxic effects on the kidney function and structure.

Is there evidence for more than two diffusion components in abdominal organs? - A magnetic resonance imaging study in healthy volunteers.

PubMed

Wurnig, Moritz C; Germann, Manon; Boss, Andreas

2018-01-01

The most commonly applied model for the description of diffusion-weighted imaging (DWI) data in perfused organs is bicompartmental intravoxel incoherent motion (IVIM) analysis. In this study, we assessed the ground truth of underlying diffusion components in healthy abdominal organs using an extensive DWI protocol and subsequent computation of apparent diffusion coefficient 'spectra', similar to the computation of previously described T 2 relaxation spectra. Diffusion datasets of eight healthy subjects were acquired in a 3-T magnetic resonance scanner using 68 different b values during free breathing (equidistantly placed in the range 0-1005 s/mm 2 ). Signal intensity curves as a function of the b value were analyzed in liver, spleen and kidneys using non-negative least-squares fitting to a distribution of decaying exponential functions with minimum amplitude energy regularization. In all assessed organs, the typical slow- and fast-diffusing components of the IVIM model were detected [liver: true diffusion D = (1.26 ± 0.01) × 10 -3 mm 2 /s, pseudodiffusion D* = (270 ± 44) × 10 -3 mm 2 /s; kidney cortex: D = (2.26 ± 0.07) × 10 -3 mm 2 /s, D* = (264 ± 78) × 10 -3 mm 2 /s; kidney medulla: D = (1.57 ± 0.28) × 10 -3 mm 2 /s, D* = (168 ± 18) × 10 -3 mm 2 /s; spleen: D = (0.91 ± 0.01) × 10 -3 mm 2 /s, D* = (69.8 ± 0.50) × 10 -3 mm 2 /s]. However, in the liver and kidney, a third component between D and D* was found [liver: D' = (43.8 ± 5.9) × 10 -3 mm 2 /s; kidney cortex: D' = (23.8 ± 11.5) × 10 -3 mm 2 /s; kidney medulla: D' = (5.23 ± 0.93) × 10 -3 mm 2 /s], whereas no third component was detected in the spleen. Fitting with a diffusion kurtosis model did not lead to a better fit of the resulting curves to the acquired data compared with apparent diffusion coefficient spectrum analysis. For a most accurate description of diffusion properties in the liver and the kidneys, a more sophisticated model seems to be required including three diffusion components. Copyright © 2017 John Wiley & Sons, Ltd.

Thermal Analyses of a Human Kidney and a Rabbit Kidney During Cryopreservation by Vitrification.

PubMed

Ehrlich, Lili E; Fahy, Gregory M; Wowk, Brian G; Malen, Jonathan A; Rabin, Yoed

2018-01-01

This study focuses on thermal analysis of the problem of scaling up from the vitrification of rabbit kidneys to the vitrification of human kidneys, where vitrification is the preservation of biological material in the glassy state. The basis for this study is a successful cryopreservation protocol for a rabbit kidney model, based on using a proprietary vitrification solution known as M22. Using the finite element analysis (FEA) commercial code ANSYS, heat transfer simulations suggest that indeed the rabbit kidney unquestionably cools rapidly enough to be vitrified based on known intrarenal concentrations of M22. Scaling up 21-fold, computer simulations suggest less favorable conditions for human kidney vitrification. In this case, cooling rates below -100 °C are sometimes slower than 1 °C/min, a rate that provides a clear-cut margin of safety at all temperatures based on the stability of rabbit kidneys in past studies. Nevertheless, it is concluded in this study that vitrifying human kidneys is possible without significant ice damage, assuming that human kidneys can be perfused with M22 as effectively as rabbit kidneys. The thermal analysis suggests that cooling rates can be further increased by a careful design of the cryogenic protocol and by tailoring the container to the shape of the kidney, in contrast to the present cylindrical container. This study demonstrates the critical need for the thermal analysis of experimental cryopreservation and highlights the unmet need for measuring the thermophysical properties of cryoprotective solutions under conditions relevant to realistic thermal histories.

DHEA supplementation to dexamethasone-treated rabbits alleviates oxidative stress in kidney-cortex and attenuates albuminuria.

PubMed

Kiersztan, Anna; Trojan, Nina; Tempes, Aleksandra; Nalepa, Paweł; Sitek, Joanna; Winiarska, Katarzyna; Usarek, Michał

2017-11-01

Our recent study has shown that dehydroepiandrosterone (DHEA) administered to rabbits partially ameliorated several dexamethasone (dexP) effects on hepatic and renal gluconeogenesis, insulin resistance and plasma lipid disorders. In the current investigation, we present the data on DHEA protective action against dexP-induced oxidative stress and albuminuria in rabbits. Four groups of adult male rabbits were used in the in vivo experiment: (1) control, (2) dexP-treated, (3) DHEA-treated and (4) both dexP- and DHEA-treated. Administration of dexP resulted in accelerated generation of renal hydroxyl free radicals (HFR) and malondialdehyde (MDA), accompanied by diminished superoxide dismutase (SOD) and catalase activities and a dramatic rise in urinary albumin/creatinine ratio. Treatment with DHEA markedly reduced dexP-induced oxidative stress in kidney-cortex due to a decline in NADPH oxidase activity and enhancement of catalase activity. Moreover, DHEA effectively attenuated dexP-evoked albuminuria. Surprisingly, dexP-treated rabbits exhibited elevation of GSH/GSSG ratio, accompanied by a decrease in glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities as well as an increase in glucose-6-phosphate dehydrogenase (G6PDH) activity. Treatment with DHEA resulted in a decline in GSH/GSSG ratio and glutathione reductase (GR) activity, accompanied by an elevation of GPx activity. Interestingly, rabbits treated with both dexP and DHEA remained the control values of GSH/GSSG ratio. As the co-administration of DHEA with dexP resulted in (i) reduction of oxidative stress in kidney-cortex, (ii) attenuation of albuminuria and (iii) normalization of glutathione redox state, DHEA might limit several undesirable renal side effects during chronic GC treatment of patients suffering from allergies, asthma, rheumatoid arthritis and lupus. Moreover, its supplementation might be particularly beneficial for the therapy of patients with glucocorticoid-induced diabetes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Is orbital volume associated with eyeball and visual cortex volume in humans?

PubMed

Pearce, Eiluned; Bridge, Holly

2013-01-01

In humans orbital volume increases linearly with absolute latitude. Scaling across mammals between visual system components suggests that these larger orbits should translate into larger eyes and visual cortices in high latitude humans. Larger eyes at high latitudes may be required to maintain adequate visual acuity and enhance visual sensitivity under lower light levels. To test the assumption that orbital volume can accurately index eyeball and visual cortex volumes specifically in humans. Structural Magnetic Resonance Imaging (MRI) techniques are employed to measure eye and orbit (n = 88) and brain and visual cortex (n = 99) volumes in living humans. Facial dimensions and foramen magnum area (a proxy for body mass) were also measured. A significant positive linear relationship was found between (i) orbital and eyeball volumes, (ii) eyeball and visual cortex grey matter volumes and (iii) different visual cortical areas, independently of overall brain volume. In humans the components of the visual system scale from orbit to eye to visual cortex volume independently of overall brain size. These findings indicate that orbit volume can index eye and visual cortex volume in humans, suggesting that larger high latitude orbits do translate into larger visual cortices.

Is orbital volume associated with eyeball and visual cortex volume in humans?

PubMed Central

Pearce, Eiluned; Bridge, Holly

2013-01-01

Background In humans orbital volume increases linearly with absolute latitude. Scaling across mammals between visual system components suggests that these larger orbits should translate into larger eyes and visual cortices in high latitude humans. Larger eyes at high latitudes may be required to maintain adequate visual acuity and enhance visual sensitivity under lower light levels. Aim To test the assumption that orbital volume can accurately index eyeball and visual cortex volumes specifically in humans. Subjects & Methods Structural Magnetic Resonance Imaging (MRI) techniques are employed to measure eye and orbit (N=88), and brain and visual cortex (N=99) volumes in living humans. Facial dimensions and foramen magnum area (a proxy for body mass) were also measured. Results A significant positive linear relationship was found between (i) orbital and eyeball volumes, (ii) eyeball and visual cortex grey matter volumes, (iii) different visual cortical areas, independently of overall brain volume. Conclusion In humans the components of the visual system scale from orbit to eye to visual cortex volume independently of overall brain size. These findings indicate that orbit volume can index eye and visual cortex volume in humans, suggesting that larger high latitude orbits do translate into larger visual cortices. PMID:23879766

The Organization of Dorsal Frontal Cortex in Humans and Macaques

PubMed Central

Mars, Rogier B.; Noonan, MaryAnn P.; Neubert, Franz-Xaver; Jbabdi, Saad; O'Reilly, Jill X.; Filippini, Nicola; Thomas, Adam G.; Rushworth, Matthew F.

2013-01-01

The human dorsal frontal cortex has been associated with the most sophisticated aspects of cognition, including those that are thought to be especially refined in humans. Here we used diffusion-weighted magnetic resonance imaging (DW-MRI) and functional MRI (fMRI) in humans and macaques to infer and compare the organization of dorsal frontal cortex in the two species. Using DW-MRI tractography-based parcellation, we identified 10 dorsal frontal regions lying between the human inferior frontal sulcus and cingulate cortex. Patterns of functional coupling between each area and the rest of the brain were then estimated with fMRI and compared with functional coupling patterns in macaques. Areas in human medial frontal cortex, including areas associated with high-level social cognitive processes such as theory of mind, showed a surprising degree of similarity in their functional coupling patterns with the frontal pole, medial prefrontal, and dorsal prefrontal convexity in the macaque. We failed to find evidence for “new” regions in human medial frontal cortex. On the lateral surface, comparison of functional coupling patterns suggested correspondences in anatomical organization distinct from those that are widely assumed. A human region sometimes referred to as lateral frontal pole more closely resembled area 46, rather than the frontal pole, of the macaque. Overall the pattern of results suggest important similarities in frontal cortex organization in humans and other primates, even in the case of regions thought to carry out uniquely human functions. The patterns of interspecies correspondences are not, however, always those that are widely assumed. PMID:23884933

Effect of 3,5,3'-triiodothyronine-induced hyperthyroidism on iodothyronine metabolism in the rat: evidence for tissue differences in metabolic responses.

PubMed

Chopra, I J; Huang, T S; Hurd, R E; Solomon, D H

1984-04-01

We studied the effect of T3-induced hyperthyroidism on the outer ring (5' or 3') monodeiodination of T4 (to T3) and 3',5'-diiodothyronine [3',5'-T2; to 3'-monoiodothyronine (3'-T1)] and on the inner ring (3 or 5) monodeiodination of 3,5-T2 (to 3-T1) by various rat tissues. Weight-matched pairs of male Sprague-Dawley rats were given either saline or T3 (20 micrograms/100 g BW daily) ip for 3 days. The metabolism of the iodothyronines was studied on day 4 in homogenates of the tissues in the presence of 25 mM dithiothreitol. Hyperthyroidism was associated with a significant (P less than 0.05) increase in T4 to T3 monodeiodinating activity in the liver (mean, 95%), kidney (mean, 60%), and heart (mean, 153%), but not in skeletal muscle, small intestine, spleen, testis, cerebral cortex, or cerebellum. The monodeiodinating activity converting 3',5'-T2 to 3'-T1 was greatly increased (P less than 0.05) in the heart (mean, 750%), spleen (mean, 462%), and skeletal muscle (mean, 167%), but not in liver, kidney, small intestine, testis, cerebral cortex, or cerebellum. In the case of liver and kidney, however, there was evidence of an activation of 3',5'-T2 monodeiodinating activity, as suggested by a significant increase in the activity in the absence of added dithiothreitol. The monodeiodination of 3,5-T2 to 3-T1 increased significantly only in the cerebral cortex (mean, 525%) and liver (mean, 69%) and not in any other tissue. The time course of the above-mentioned changes in iodothyronine metabolism was studied in groups of rats (five per group) given T3 (20 micrograms 100 g BW-1 day-1) 6-72 h before death. Significant increases in 3',5'-T2 (to 3'-T1) monodeiodination in the heart and 3,5-T2 (to 3-T1) monodeiodination in the cerebral cortex were evident within 6 h of T3 administration. Changes in T4 to T3 monodeiodinating activity in the kidney and liver, however, did not become statistically significant until 24 and 72 h, respectively. The various effects of T3 on the tissues became maximal between 48 and 72 h after the initiation of T3 treatment. Our data suggest that most tissues, including some that have been considered unresponsive to thyroid hormones, e.g. brain and spleen, demonstrate substantial metabolic changes after T3 administration. The tissue responses are variable in degree; in some instances, they are specific for the substrate and type of tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

The auditory representation of speech sounds in human motor cortex

PubMed Central

Cheung, Connie; Hamilton, Liberty S; Johnson, Keith; Chang, Edward F

2016-01-01

In humans, listening to speech evokes neural responses in the motor cortex. This has been controversially interpreted as evidence that speech sounds are processed as articulatory gestures. However, it is unclear what information is actually encoded by such neural activity. We used high-density direct human cortical recordings while participants spoke and listened to speech sounds. Motor cortex neural patterns during listening were substantially different than during articulation of the same sounds. During listening, we observed neural activity in the superior and inferior regions of ventral motor cortex. During speaking, responses were distributed throughout somatotopic representations of speech articulators in motor cortex. The structure of responses in motor cortex during listening was organized along acoustic features similar to auditory cortex, rather than along articulatory features as during speaking. Motor cortex does not contain articulatory representations of perceived actions in speech, but rather, represents auditory vocal information. DOI: http://dx.doi.org/10.7554/eLife.12577.001 PMID:26943778

Aging and Gene Expression in the Primate Brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.

2005-02-18

It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes inmore » the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.« less

Clinical protocol levels are required in laboratory animal surgery when using medical devices: experiences with ureteral replacement surgery in goats.

PubMed

de Jonge, Paul K J D; Sloff, Marije; Janke, Heinz P; Kortmann, Barbara B M; de Gier, Robert P E; Geutjes, Paul J; Oosterwijk, Egbert; Feitz, Wout F J

2017-10-01

It is common to test medical devices in large animal studies that are or could also be used in humans. In this short report we describe the use of a ureteral J-stent for the evaluation of biodegradable tubular constructs for tissue reconstruction, and the regeneration of ureters in Saanen goats. Similarly to a previous study in pigs, the ureteral J-stent was blindly inserted until some resistance was met. During evaluation of the goats after three months, perforation of the renal cortex by the stent was observed in four out of seven animals. These results indicated that blind stent placement was not possible in goats. In four new goats, clinical protocols were followed using X-ray and iodinated contrast fluids to visualize the kidney and stent during stent placement. With this adaptation the stents were successfully placed in the kidneys of these four new goats with minimal additional effort. It is likely that other groups in other fields ran into similar problems that could have been avoided by following clinical protocols. Therefore, we would like to stress the importance of following clinical protocols when using medical devices in animals to prevent unnecessary suffering and to reduce the number of animals needed.

Antiaging Gene Klotho Regulates Adrenal CYP11B2 Expression and Aldosterone Synthesis

PubMed Central

Zhou, Xiaoli; Chen, Kai; Wang, Yongjun; Schuman, Mariano; Lei, Han

2016-01-01

Deficiency of the antiaging gene Klotho (KL) induces renal damage and hypertension through unknown mechanisms. In this study, we assessed whether KL regulates expression of CYP11B2, a key rate–limiting enzyme in aldosterone synthesis, in adrenal glands. We found that haplodeficiency of KL(+/−) in mice increased the plasma level of aldosterone by 16 weeks of age, which coincided with spontaneous and persistent elevation of BP. Blockade of aldosterone actions by eplerenone reversed KL deficiency–induced hypertension and attenuated the kidney damage. Protein expression of CYP11B2 was upregulated in adrenal cortex of KL(+/−) mice. KL and CYP11B2 proteins colocalized in adrenal zona glomerulosa cells. Silencing of KL upregulated and overexpression of KL downregulated CYP11B2 expression in human adrenocortical cells. Notably, silencing of KL decreased expression of SF-1, a negative transcription factor of CYP11B2, but increased phosphorylation of ATF2, a positive transcription factor of CYP11B2, which may contribute to upregulation of CYP11B2 expression. Therefore, these results show that KL regulates adrenal CYP11B2 expression. KL deficiency–induced spontaneous hypertension and kidney damage may be partially attributed to the upregulation of CYP11B2 expression and aldosterone synthesis. PMID:26471128

Expression of peroxisomal proliferator-activated receptors and retinoid X receptors in the kidney.

PubMed

Yang, T; Michele, D E; Park, J; Smart, A M; Lin, Z; Brosius, F C; Schnermann, J B; Briggs, J P

1999-12-01

The discovery that 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) is a ligand for the gamma-isoform of peroxisome proliferator-activated receptor (PPAR) suggests nuclear signaling by prostaglandins. Studies were undertaken to determine the nephron localization of PPAR isoforms and their heterodimer partners, retinoid X receptors (RXR), and to evaluate the function of this system in the kidney. PPARalpha mRNA, determined by RT-PCR, was found predominately in cortex and further localized to proximal convoluted tubule (PCT); PPARgamma was abundant in renal inner medulla, localized to inner medullary collecting duct (IMCD) and renal medullary interstitial cells (RMIC); PPARbeta, the ubiquitous form of PPAR, was abundant in all nephron segments examined. RXRalpha was localized to PCT and IMCD, whereas RXRbeta was expressed in almost all nephron segments examined. mRNA expression of acyl-CoA synthase (ACS), a known PPAR target gene, was stimulated in renal cortex of rats fed with fenofibrate, but the expression was not significantly altered in either cortex or inner medulla of rats fed with troglitazone. In cultured RMIC cells, both troglitazone and 15d-PGJ2 significantly inhibited cell proliferation and dramatically altered cell shape by induction of cell process formation. We conclude that PPAR and RXR isoforms are expressed in a nephron segment-specific manner, suggesting distinct functions, with PPARalpha being involved in energy metabolism through regulating ACS in PCT and with PPARgamma being involved in modulating RMIC growth and differentiation.

The influence of manganese treatment on the distribution of metal elements in rats and the protection by sodium para-amino salicylic acid.

PubMed

Yuan, Zong-Xiang; Chen, Hai-Bin; Li, Shao-Jun; Huang, Xiao-Wei; Mo, Yu-Huan; Luo, Yi-Ni; He, Sheng-Nan; Deng, Xiang-Fa; Lu, Guo-Dong; Jiang, Yue-Ming

2016-07-01

Manganese (Mn) overexposure induced neurological damages, which could be potentially protected by sodium para-aminosalicylic acid (PAS-Na). In this study, we systematically detected the changes of divalent metal elements in most of the organs and analyzed the distribution of the metals in Mn-exposed rats and the protection by PAS-Na. Sprague Dawley (SD) rats received intraperitoneal injections of 15mg/kg MnCl2·4H2O (5d/week for 3 weeks), followed by subcutaneous (back) injections of PAS-Na (100 and 200mg/kg, everyday for 5 weeks). The concentrations of Mn and other metal elements [Iron (Fe), Copper (Cu), Zinc (Zn), Magnesium (Mg), Calcium (Ca)] in major organs (liver, spleen, kidney, thighbone and iliac bone, cerebral cortex, hippocampus and testes) and blood by Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). The results showed that Mn overexposure significantly increased Mn in most organs, Fe and Zn in liver, Fe and Mg in blood; however decreased Fe, Cu, Zn, Mg and Ca in cortex, Cu and Zn in kidney, Cu and Mg in iliac bone, and Zn in blood. In contrast, PAS-Na treatment restored most changes particularly in cortex. In conclusion, excessive Mn exposure disturbed the balance of other metal elements but PAS-Na post-treatments could restore these alterations. Copyright © 2016 Elsevier GmbH. All rights reserved.

Renoprotective Effects of Atorvastatin in Diabetic Mice: Downregulation of RhoA and Upregulation of Akt/GSK3

PubMed Central

Bruder-Nascimento, Thiago; Callera, Glaucia; Montezano, Augusto Cesar; Antunes, Tayze T.; He, Ying; Cat, Aurelie Nguyen Dinh; Ferreira, Nathanne S.; Barreto, Pedro A.; Olivon, Vânia C.; Tostes, Rita C.; Touyz, Rhian M.

2016-01-01

Potential benefits of statins in the treatment of chronic kidney disease beyond lipid-lowering effects have been described. However, molecular mechanisms involved in renoprotective actions of statins have not been fully elucidated. We questioned whether statins influence development of diabetic nephropathy through reactive oxygen species, RhoA and Akt/GSK3 pathway, known to be important in renal pathology. Diabetic mice (db/db) and their control counterparts (db/+) were treated with atorvastatin (10 mg/Kg/day, p.o., for 2 weeks). Diabetes-associated renal injury was characterized by albuminuria (albumin:creatinine ratio, db/+: 3.2 ± 0.6 vs. db/db: 12.5 ± 3.1*; *P<0.05), increased glomerular/mesangial surface area, and kidney hypertrophy. Renal injury was attenuated in atorvastatin-treated db/db mice. Increased ROS generation in the renal cortex of db/db mice was also inhibited by atorvastatin. ERK1/2 phosphorylation was increased in the renal cortex of db/db mice. Increased renal expression of Nox4 and proliferating cell nuclear antigen, observed in db/db mice, were abrogated by statin treatment. Atorvastatin also upregulated Akt/GSK3β phosphorylation in the renal cortex of db/db mice. Our findings suggest that atorvastatin attenuates diabetes-associated renal injury by reducing ROS generation, RhoA activity and normalizing Akt/GSK3β signaling pathways. The present study provides some new insights into molecular mechanisms whereby statins may protect against renal injury in diabetes. PMID:27649495

pH imaging of mouse kidneys in vivo using a frequency-dependent paraCEST agent

PubMed Central

Wu, Yunkou; Zhang, Shanrong; Soesbe, Todd C.; Yu, Jing; Vinogradov, Elena; Lenkinski, Robert E.; Sherry, A. Dean

2015-01-01

Purpose This study explored the feasibility of using a pH responsive paraCEST agent to image the pH gradient in kidneys of healthy mice. Methods CEST signals were acquired on an Agilent 9.4 T small animal MRI system using a steady-state gradient echo pulse sequence after a bolus injection of agent. The magnetic field inhomogeneity across each kidney was corrected using the WASSR method and pH maps were calculated by measuring the frequency of water exchange signal arising from the agent. Results Dynamic CEST studies demonstrated that the agent was readily detectable in kidneys only between 4 to 12 min post-injection. The CEST images showed a higher signal intensity in the pelvis and calyx regions and lower signal intensity in the medulla and cortex regions. The pH maps reflected tissue pH values spanning from 6.0 to 7.5 in kidneys of healthy mice. Conclusion This study demonstrated that pH maps of the kidney can be imaged in vivo by measuring the pH-dependent chemical shift of a single water exchange CEST peak without prior knowledge of the agent concentration in vivo. The results demonstrate the potential of using a simple frequency-dependent paraCEST agent for mapping tissue pH in vivo. PMID:26173637

Implied motion because of instability in Hokusai Manga activates the human motion-sensitive extrastriate visual cortex: an fMRI study of the impact of visual art.

PubMed

Osaka, Naoyuki; Matsuyoshi, Daisuke; Ikeda, Takashi; Osaka, Mariko

2010-03-10

The recent development of cognitive neuroscience has invited inference about the neurosensory events underlying the experience of visual arts involving implied motion. We report functional magnetic resonance imaging study demonstrating activation of the human extrastriate motion-sensitive cortex by static images showing implied motion because of instability. We used static line-drawing cartoons of humans by Hokusai Katsushika (called 'Hokusai Manga'), an outstanding Japanese cartoonist as well as famous Ukiyoe artist. We found 'Hokusai Manga' with implied motion by depicting human bodies that are engaged in challenging tonic posture significantly activated the motion-sensitive visual cortex including MT+ in the human extrastriate cortex, while an illustration that does not imply motion, for either humans or objects, did not activate these areas under the same tasks. We conclude that motion-sensitive extrastriate cortex would be a critical region for perception of implied motion in instability.

Chronic methylmercurialism in a horse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seawright, A.A.; Roberts, M.C.; Costigan, P.

1978-02-01

Chronic methylmercurialism was produced in a horse given 10 g methylmercury chloride over 10 weeks. Neurological signs, particularly proprioceptive disturbances, were apparent by the final week of dosing and became more severe thereafter. An exudative dermatitis, a reluctance to move, weight loss, reduced appetite and dullness were among the earlier clinical signs, and renal changes characterized by a steadily increasing BUN and glucosuria were detected later. Pathological lesions were confined to the kidneys and the nervous system. There was mild neuronal degeneration in the cerebral cortex and in the cerebellar cortex, axonal demyelination in the dorsal columns of the spinalmore » cord and extensive degeneration of ganglion cells in the dorsal root ganglia. The blood organic mercury level, which had plateaued in the second month, increased rapidly in the last weeks of dosing with a sharp rise terminally. This pattern was repeated for the much lower inorganic mercury levels except for a terminal decrease. The proportion of inorganic mercury was five times greater in the dorsal root ganglia than elsewhere in the CNS, although total mercury levels were similar. Highest tissue mercury levels were found in the liver and kidneys, over 50% being in the form of inorganic mercury. As dealkylation of the methylmercury appeared to be more efficient in the dorsal root ganglia and the kidneys, inorganic mercury derived therefrom may have been responsible for some of the clinical and pathological features of this intoxication in the horse. 21 references, 6 figures, 2 tables.« less

Magnetic resonance evaluation of hydronephrosis in the dog

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thickman, D.; Kundel, H.; Biery, D.

1984-07-01

The ability of magnetic resonance (MR) imaging to detect and distinguish various stages of obstruction in the canine kidney was investigated. MR images were obtained at acute, subacute, and chronic stages of experimentally produced hydronephrosis. The renal cortex was distinguished from the renal medulla in the normal dog and in the acute and subacute stages of hydronephrosis. T1 relaxation times of the renal cortex and medulla were measured in vitro in 14 normal and nine experimental animals. These values were used to compute the amount of tissue contrast between the cortex and medulla and were compared with the degree ofmore » corticomedullary differentiation seen in the image. A relationship was noted between increasing T1 values and increasing water content. Corticomedullary contrast decreased with obstruction. The variation in corticomedullary image contracts may be useful for assessing the duration of hydronephrosis.« less

COMPLEMENT FIXATION IN DISEASED TISSUES

PubMed Central

Burkholder, Peter M.

1961-01-01

An immunohistologic complement fixation test has been used in an effort to detect immune complexes in sections of kidney from rats injected with rabbit anti-rat kidney serum and in sections of biopsied kidneys from four humans with membranous glomerulonephritis. Sections of the rat and human kidneys were treated with fluorescein-conjugated anti-rabbit globulin or antihuman globulin respectively. Adjacent sections in each case were incubated first with fresh guinea pig serum and then in a second step were treated with fluorescein-conjugated antibodies against fixed guinea pig complement to detect sites of fixation of the complement. It was demonstrated that the sites of rabbit globulin in glomerular capillary walls of the rat kidneys and the sites of localized human globulin in thickened glomerular capillary walls and swollen glomerular endothelial cells of the human kidneys were the same sites in which guinea pig complement was fixed in vitro. It was concluded from these studies that rabbit nephrotoxic antibodies localize in rat glomeruli in complement-fixing antigen-antibody complexes. Furthermore, it was concluded that the deposits of human globulin in the glomeruli of the human kidneys behaved like antibody globulin in complement-fixing antigen-antibody complexes. The significance of demonstrating complement-fixing immune complexes in certain diseased tissues is discussed in regard to determination of the causative role of allergic reactions in disease. PMID:19867205

Rapid cortical oscillations and early motor activity in premature human neonate.

PubMed

Milh, Mathieu; Kaminska, Anna; Huon, Catherine; Lapillonne, Alexandre; Ben-Ari, Yehezkel; Khazipov, Rustem

2007-07-01

Delta-brush is the dominant pattern of rapid oscillatory activity (8-25 Hz) in the human cortex during the third trimester of gestation. Here, we studied the relationship between delta-brushes in the somatosensory cortex and spontaneous movements of premature human neonates of 29-31 weeks postconceptional age using a combination of scalp electroencephalography and monitoring of motor activity. We found that sporadic hand and foot movements heralded the appearance of delta-brushes in the corresponding areas of the cortex (lateral and medial regions of the contralateral central cortex, respectively). Direct hand and foot stimulation also reliably evoked delta-brushes in the same areas. These results suggest that sensory feedback from spontaneous fetal movements triggers delta-brush oscillations in the central cortex in a somatotopic manner. We propose that in the human fetus in utero, before the brain starts to receive elaborated sensory input from the external world, spontaneous fetal movements provide sensory stimulation and drive delta-brush oscillations in the developing somatosensory cortex contributing to the formation of cortical body maps.

The Munich MIDY Pig Biobank - A unique resource for studying organ crosstalk in diabetes.

PubMed

Blutke, Andreas; Renner, Simone; Flenkenthaler, Florian; Backman, Mattias; Haesner, Serena; Kemter, Elisabeth; Ländström, Erik; Braun-Reichhart, Christina; Albl, Barbara; Streckel, Elisabeth; Rathkolb, Birgit; Prehn, Cornelia; Palladini, Alessandra; Grzybek, Michal; Krebs, Stefan; Bauersachs, Stefan; Bähr, Andrea; Brühschwein, Andreas; Deeg, Cornelia A; De Monte, Erica; Dmochewitz, Michaela; Eberle, Caroline; Emrich, Daniela; Fux, Robert; Groth, Frauke; Gumbert, Sophie; Heitmann, Antonia; Hinrichs, Arne; Keßler, Barbara; Kurome, Mayuko; Leipig-Rudolph, Miriam; Matiasek, Kaspar; Öztürk, Hazal; Otzdorff, Christiane; Reichenbach, Myriam; Reichenbach, Horst Dieter; Rieger, Alexandra; Rieseberg, Birte; Rosati, Marco; Saucedo, Manuel Nicolas; Schleicher, Anna; Schneider, Marlon R; Simmet, Kilian; Steinmetz, Judith; Übel, Nicole; Zehetmaier, Patrizia; Jung, Andreas; Adamski, Jerzy; Coskun, Ünal; Hrabě de Angelis, Martin; Simmet, Christian; Ritzmann, Mathias; Meyer-Lindenberg, Andrea; Blum, Helmut; Arnold, Georg J; Fröhlich, Thomas; Wanke, Rüdiger; Wolf, Eckhard

2017-08-01

The prevalence of diabetes mellitus and associated complications is steadily increasing. As a resource for studying systemic consequences of chronic insulin insufficiency and hyperglycemia, we established a comprehensive biobank of long-term diabetic INS C94Y transgenic pigs, a model of mutant INS gene-induced diabetes of youth (MIDY), and of wild-type (WT) littermates. Female MIDY pigs (n = 4) were maintained with suboptimal insulin treatment for 2 years, together with female WT littermates (n = 5). Plasma insulin, C-peptide and glucagon levels were regularly determined using specific immunoassays. In addition, clinical chemical, targeted metabolomics, and lipidomics analyses were performed. At age 2 years, all pigs were euthanized, necropsied, and a broad spectrum of tissues was taken by systematic uniform random sampling procedures. Total beta cell volume was determined by stereological methods. A pilot proteome analysis of pancreas, liver, and kidney cortex was performed by label free proteomics. MIDY pigs had elevated fasting plasma glucose and fructosamine concentrations, C-peptide levels that decreased with age and were undetectable at 2 years, and an 82% reduced total beta cell volume compared to WT. Plasma glucagon and beta hydroxybutyrate levels of MIDY pigs were chronically elevated, reflecting hallmarks of poorly controlled diabetes in humans. In total, ∼1900 samples of different body fluids (blood, serum, plasma, urine, cerebrospinal fluid, and synovial fluid) as well as ∼17,000 samples from ∼50 different tissues and organs were preserved to facilitate a plethora of morphological and molecular analyses. Principal component analyses of plasma targeted metabolomics and lipidomics data and of proteome profiles from pancreas, liver, and kidney cortex clearly separated MIDY and WT samples. The broad spectrum of well-defined biosamples in the Munich MIDY Pig Biobank that will be available to the scientific community provides a unique resource for systematic studies of organ crosstalk in diabetes in a multi-organ, multi-omics dimension.

Inhibition of NA+/H+ Exchanger 1 Attenuates Renal Dysfunction Induced by Advanced Glycation End Products in Rats

PubMed Central

Li, Peng; Chen, Geng-Rong; Wang, Fu; Xu, Ping; Liu, Li-Ying; Yin, Ya-Ling; Wang, Shuang-Xi

2016-01-01

It has been recognized that sodium hydrogen exchanger 1 (NHE1) is involved in the development of diabetic nephropathy. The role of NHE1 in kidney dysfunction induced by advanced glycation end products (AGEs) remains unknown. Renal damage was induced by AGEs via tail vein injections in rats. Function and morphology of kidney were determined. Compared to vehicle- or BSA-treated rats, AGEs caused abnormalities of kidney structures and functions in rats, accompanied with higher MDA level and lower GSH content. Gene expressions of NHE1 gene and TGF-β1 in the renal cortex and urine were also increased in AGEs-injected rats. Importantly, all these detrimental effects induced by AGEs were reversed by inhibition of NHE1 or suppression of oxidative stress. These pieces of data demonstrated that AGEs may activate NHE1 to induce renal damage, which is related to TGF-β1. PMID:26697498

Monitoring hemodynamics and oxygenation of the kidney in rats by a combined near-infrared spectroscopy and invasive probe approach

NASA Astrophysics Data System (ADS)

Grosenick, Dirk; Cantow, Kathleen; Arakelyan, Karen; Wabnitz, Heidrun; Flemming, Bert; Skalweit, Angela; Ladwig, Mechthild; Macdonald, Rainer; Niendorf, Thoralf; Seeliger, Erdmann

2015-07-01

We have developed a hybrid approach to investigate the dynamics of perfusion and oxygenation in the kidney of rats under pathophysiologically relevant conditions. Our approach combines near-infrared spectroscopy to quantify hemoglobin concentration and oxygen saturation in the renal cortex, and an invasive probe method for measuring total renal blood flow by an ultrasonic probe, perfusion by laser-Doppler fluxmetry, and tissue oxygen tension via fluorescence quenching. Hemoglobin concentration and oxygen saturation were determined from experimental data by a Monte Carlo model. The hybrid approach was applied to investigate and compare temporal changes during several types of interventions such as arterial and venous occlusions, as well as hyperoxia, hypoxia and hypercapnia induced by different mixtures of the inspired gas. The approach was also applied to study the effects of the x-ray contrast medium iodixanol on the kidney.

Small Intestinal Submucosa Plug for Closure of Dilated Nephrostomy Tracts: A Pilot Study in Swine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kakizawa, Hideyaki; Conlin, M. J.; Pavcnik, Dusan, E-mail: pavcnikd@ohsu.edu

2010-06-15

The aim of this study was to evaluate efficacy of a plug made of small intestinal submucosa (SIS) for closure of dilated nephrostomy tract in the kidney after nephroscopy. Ten kidneys in 5 swine had nephrostomy tracts dilated up to 8 mm. The SIS plug was placed into the dilated renal cortex under nephroscopic control. Follow-up arteriograms, retrograde pyelograms, and macroscopic and histologic studies at 24 h (n = 4), 6 weeks (n = 2), and 3 months (n = 4) were performed to evaluate the efficacy of the plug. The SIS plug effectively closed the dilated nephrostomy tract. Follow-upmore » studies showed minimal changes of the kidneys, except for 1 small infarction, regarding inflammatory and foreign-body reactions and progressive scarring of the SIS. SIS plug is effective for occlusion of dilated nephrostomy tract after nephroscopy. Its efficacy should be compared with other therapeutic options.« less

"Ecstasy" toxicity to adolescent rats following an acute low binge dose.

PubMed

Teixeira-Gomes, Armanda; Costa, Vera Marisa; Feio-Azevedo, Rita; Duarte, José Alberto; Duarte-Araújo, Margarida; Fernandes, Eduarda; Bastos, Maria de Lourdes; Carvalho, Félix; Capela, João Paulo

2016-06-28

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a worldwide drug of abuse commonly used by adolescents. Most reports focus on MDMA's neurotoxicity and use high doses in adult animals, meanwhile studies in adolescents are scarce. We aimed to assess in rats the acute MDMA toxicity to the brain and peripheral organs using a binge dose scheme that tries to simulate human adolescent abuse. Adolescent rats (postnatal day 40) received three 5 mg/kg doses of MDMA (estimated equivalent to two/three pills in a 50 kg adolescent), intraperitoneally, every 2 h, while controls received saline. After 24 h animal sacrifice took place and collection of brain areas (cerebellum, hippocampus, frontal cortex and striatum) and peripheral organs (liver, heart and kidneys) occurred. Significant hyperthermia was observed after the second and third MDMA doses, with mean increases of 1 °C as it occurs in the human scenario. MDMA promoted ATP levels fall in the frontal cortex. No brain oxidative stress-related changes were observed after MDMA. MDMA-treated rat organs revealed significant histological tissue alterations including vascular congestion, but no signs of apoptosis or necrosis were found, which was corroborated by the lack of changes in plasma biomarkers and tissue caspases. In peripheral organs, MDMA did not affect significantly protein carbonylation, glutathione, or ATP levels, but liver presented a higher vulnerability as MDMA promoted an increase in quinoprotein levels. Adolescent rats exposed to a moderate MDMA dose, presented hyperthermia and acute tissue damage to peripheral organs without signs of brain oxidative stress.

Hazards to wildlife from soil-borne cadmium reconsidered

USGS Publications Warehouse

Beyer, W.N.

2000-01-01

Cadmium is a toxic element that should be included in environmental risk assessments of contaminated soils. This paper argues, however, that hazards to wildlife from cadmium have often been overstated. The literature contains only meager evidence that wild animals have been seriously harmed by cadmium, even at severely contaminated sites. Although some researchers have reported that wildlife have accumulated concentrations of cadmium in their kidneys that were above suggested injury thresholds, the thresholds may be disputed, since they were well below the World Health Organization criterion of 200 mg/kg (wet weight) of cadmium in the renal cortex for protecting human health. Recent risk assessments have concluded that soil cadmium concentrations less than 1 mg/kg are toxic to soil organisms and wildlife, which implies that background concentrations of cadmium naturally found in soils are hazardous. An examination of the databases used to support these assessments suggested that the toxicity of cadmium has been exaggerated.

Characterisation of the canine rod-cone dysplasia type one gene (rod photoreceptor cGMP phosphodiesterase beta subunit (PDEB)) - a model for human retinitis pigmentosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clements, P.J.M.; Gregory, C.Y.; Petersen-Jones, S.M.

1994-09-01

Rod-cone dysplasia type one (rod-1) is an early onset, autosomal recessive retinal dystrophy segregating in the Irish setter breed. It is a model for certain forms of human autosomal recessive retinitis pigmentosa (arRP) caused by mutations in the same gene, PDEB. We confirmed the codon 807 Trp to Stop mutation and were the first to show cosegregation of the mutant allele with disease in a pedigree. We believe that this currently represents the best animal model available for some aspects of arRP, since canine tissues are relatively easy to access compared to human and yet the canine eye is ofmore » comparable size, unlike that of the rd mouse. This facilitates therapeutic intervention particularly at the subretinal level. In order to more fully investigate this model we have been characterizing the PDEB gene in the normal dog. Using PCR we have partially mapped the intron/exon structure, demonstrating a very high degree of evolutionary conservation with the mouse and human genes. RT-PCR has been used to reveal expression in a variety of neural and non-neural tissues. A PCR product spanning exons 19 to 22 (which also contains the site for the rcd-1 mutation) is detected in retina but also in tissues such as visual cortex, cerebral cortex, cerebellum, lateral geniculate nucleus, adrenal gland, lung, kidney and ovary. All of these tissues gave a negative result with primers for rds/peripherin, a gene which is expressed in rods and cones. This raises interesting questions about the regulation of PDEB transcripts which is initially being investigated by Northern analysis. In addition, anchored PCR techniques have generated upstream genomic sequences and we are currently mapping the 5{prime} extent of the mRNA transcript in the retina. This will facilitate the analysis of potential upstream promoter elements involved in directing expression.« less

Stereological assessment of normal Persian squirrels (Sciurus anomalus) kidney.

PubMed

Akbari, Mohsen; Goodarzi, Nader; Tavafi, Majid

2017-03-01

The functions of the mammalian kidney are closely related to its structure. This suggests that renal function can be completely characterized by accurate knowledge of its quantitative morphological features. The aim of this study was to investigate the histomorphometric features of the kidney using design-based and unbiased stereological methods in the Persian squirrel (Sciurus anomalus), which is the only representative of the Sciuridae family in the Middle East. The left kidneys of five animals were examined. Total volume of the kidney, cortex, and medulla were determined to be 960.75 ± 87.4, 754.31 ± 77.09 and 206.1 ± 16.89 mm 3 , respectively. The glomerular number was 32844.03 ± 1069.19, and the total glomerular volume was estimated to be 36.7 ± 1.45 mm 3 . The volume and length of the proximal convoluted tubule were estimated at 585.67 ± 60.7 mm 3 and 328.8 ± 14.8 m, respectively, with both values being greater than those reported in the rat kidney. The volume and length of the distal convoluted tubule were calculated at 122.34 ± 7.38 mm 3 and 234.4 ± 17.45 m, respectively, which are also greater than those reported in the rat kidney. Despite the comparable body weight, the total number and mean individual volume of glomeruli in the Persian squirrel kidney were greater than those in the rat kidney. Overall, the stereological variables of the kidneys elucidated in this study are exclusive to the Persian squirrel. Our findings, together with future renal physiological data, will contribute to a better understanding of the renal structure-function relationship in the Persian squirrel.

A method to facilitate and monitor expression of exogenous genes in the rat kidney using plasmid and viral vectors

PubMed Central

Corridon, Peter R.; Rhodes, George J.; Leonard, Ellen C.; Basile, David P.; Gattone, Vincent H.; Bacallao, Robert L.

2013-01-01

Gene therapy has been proposed as a novel alternative to treat kidney disease. This goal has been hindered by the inability to reliably deliver transgenes to target cells throughout the kidney, while minimizing injury. Since hydrodynamic forces have previously shown promising results, we optimized this approach and designed a method that utilizes retrograde renal vein injections to facilitate transgene expression in rat kidneys. We show, using intravital fluorescence two-photon microscopy, that fluorescent albumin and dextrans injected into the renal vein under defined conditions of hydrodynamic pressure distribute broadly throughout the kidney in live animals. We found injection parameters that result in no kidney injury as determined by intravital microscopy, histology, and serum creatinine measurements. Plasmids, baculovirus, and adenovirus vectors, designed to express EGFP, EGFP-actin, EGFP-occludin, EGFP-tubulin, tdTomato-H2B, or RFP-actin fusion proteins, were introduced into live kidneys in a similar fashion. Gene expression was then observed in live and ex vivo kidneys using two-photon imaging and confocal laser scanning microscopy. We recorded widespread fluorescent protein expression lasting more than 1 mo after introduction of transgenes. Plasmid and adenovirus vectors provided gene transfer efficiencies ranging from 50 to 90%, compared with 10–50% using baculovirus. Using plasmids and adenovirus, fluorescent protein expression was observed 1) in proximal and distal tubule epithelial cells; 2) within glomeruli; and 3) within the peritubular interstitium. In isolated kidneys, fluorescent protein expression was observed from the cortex to the papilla. These results provide a robust approach for gene delivery and the study of protein function in live mammal kidneys. PMID:23467422

MR diffusion tensor imaging of normal kidneys.

PubMed

Wang, Wen-juan; Pui, Margaret H; Guo, Yan; Hu, Xiao-shu; Wang, Huan-jun; Yang, Dong

2014-11-01

To assess the feasibility of diffusion tensor imaging (DTI) of normal kidneys and the influence of hydration state. Ten healthy volunteers underwent renal DTI after fasting for 12 hours and 4 hours, without fasting, and following water diuresis. Medullary and cortical apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured and compared in the four different states of hydration. DTI was performed with a 3T magnetic resonance imaging (MRI) system using fat-saturated single-shot spin-echo echo planar imaging sequence. ADC of normal cortex (2.387 ± 0.081 × 10(-3) mm(2) /s) was significantly higher (t = 20.126, P = 0) than that of medulla (1.990 ± 0.063 × 10(-3) mm(2) /s). The FA value of normal cortex (0.282 ± 0.017) was significantly lower (t = -42.713, P = 0) than that of medulla (0.447 ± 0.022). The ADC and FA values of the left renal cortex (2.404 ± 0.082 × 10(-3) mm(2) /s, 0.282 ± 0.017) and medulla (2.002 ± 0.081 × 10(-3) mm(2) /s, 0.452 ± 0.024) were not significantly different (P > 0.05) from those of right renal cortex (2.369 ± 0.080 × 10(-3) mm(2) /s, 0.283 ± 0.018) and medulla (1.978 ± 0.039 × 10(-3) mm(2) /s, 0.443 ± 0.019). Values for ADC (×10(-3) mm(2) /s) and FA in the 12-hour fasting, 4-hour fasting, nonfasting, and water diuresis states were 2.372 ± 0.095 and 0.278 ± 0.018, 2.387 ± 0.081 and 0.282 ± 0.017, 2.416 ± 0.051 and 0.279 ± 0.023, 2.421 ± 0.068, and 0.270 ± 0.021, respectively, in cortex, 1.972 ± 0.084 and 0.438 ± 0.014, 1.990 ± 0.063 and 0.447 ± 0.022, 2.021 ± 0.081 and 0.450 ± 0.031, 2.016 ± 0.076 and 0.449 ± 0.028, respectively, in medulla. The ADC and FA values in different hydration states were not significantly different (P > 0.05). DTI of normal kidneys is feasible with reproducible ADC and FA values independent of hydration states. © 2013 Wiley Periodicals, Inc.

Detection and Clinical Patterns of Nephron Hypertrophy and Nephrosclerosis Among Apparently Healthy Adults.

PubMed

Denic, Aleksandar; Alexander, Mariam P; Kaushik, Vidhu; Lerman, Lilach O; Lieske, John C; Stegall, Mark D; Larson, Joseph J; Kremers, Walter K; Vrtiska, Terri J; Chakkera, Harini A; Poggio, Emilio D; Rule, Andrew D

2016-07-01

Even among ostensibly healthy adults, there is often mild pathology in the kidney. The detection of kidney microstructural variation and pathology by imaging and the clinical pattern associated with these structural findings is unclear. Cross-sectional (clinical-pathologic correlation). Living kidney donors at Mayo Clinic (Minnesota and Arizona sites) and Cleveland Clinic 2000 to 2011. Predonation kidney function, risk factors, and contrast computed tomographic scan of the kidneys. These scans were segmented for cortical volume and medullary volume, reviewed for parenchymal cysts, and scored for kidney surface roughness. Nephrosclerosis (glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis) and nephron size (glomerular volume, mean profile tubular area, and cortical volume per glomerulus) determined from an implantation biopsy of the kidney cortex at donation. Among 1,520 living kidney donors, nephrosclerosis associated with increased kidney surface roughness, cysts, and smaller cortical to medullary volume ratio. Larger nephron size (nephron hypertrophy) associated with larger cortical volume. Nephron hypertrophy and larger cortical volume associated with higher systolic blood pressure, glomerular filtration rate, and urine albumin excretion; larger body mass index; higher serum uric acid level; and family history of end-stage renal disease. Both nephron hypertrophy and nephrosclerosis associated with older age and mild hypertension. The net effect of both nephron hypertrophy and nephrosclerosis associating with cortical volume was that nephron hypertrophy diminished volume loss with age-related nephrosclerosis and fully negated volume loss with mild hypertension-related nephrosclerosis. Kidney donors are selected on health, restricting the spectrum of pathologic findings. Kidney biopsies in living donors are a small tissue sample leading to imprecise estimates of structural findings. Among apparently healthy adults, the microstructural findings of nephron hypertrophy and nephrosclerosis differ in their associations with kidney function, macrostructure, and risk factors. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Mapping Prefrontal Cortex Functions in Human Infancy

ERIC Educational Resources Information Center

Grossmann, Tobias

2013-01-01

It has long been thought that the prefrontal cortex, as the seat of most higher brain functions, is functionally silent during most of infancy. This review highlights recent work concerned with the precise mapping (localization) of brain activation in human infants, providing evidence that prefrontal cortex exhibits functional activation much…

Intraoperative intrinsic optical imaging of human somatosensory cortex during neurosurgical operations.

PubMed

Sato, Katsushige; Nariai, Tadashi; Momose-Sato, Yoko; Kamino, Kohtaro

2017-07-01

Intrinsic optical imaging as developed by Grinvald et al. is a powerful technique for monitoring neural function in the in vivo central nervous system. The advent of this dye-free imaging has also enabled us to monitor human brain function during neurosurgical operations. We briefly describe our own experience in functional mapping of the human somatosensory cortex, carried out using intraoperative optical imaging. The maps obtained demonstrate new additional evidence of a hierarchy for sensory response patterns in the human primary somatosensory cortex.

The Piriform Cortex and Human Focal Epilepsy

PubMed Central

Vaughan, David N.; Jackson, Graeme D.

2014-01-01

It is surprising that the piriform cortex, when compared to the hippocampus, has been given relatively little significance in human epilepsy. Like the hippocampus, it has a phylogenetically preserved three-layered cortex that is vulnerable to excitotoxic injury, has broad connections to both limbic and cortical areas, and is highly epileptogenic – being critical to the kindling process. The well-known phenomenon of early olfactory auras in temporal lobe epilepsy highlights its clinical relevance in human beings. Perhaps because it is anatomically indistinct and difficult to approach surgically, as it clasps the middle cerebral artery, it has, until now, been understandably neglected. In this review, we emphasize how its unique anatomical and functional properties, as primary olfactory cortex, predispose it to involvement in focal epilepsy. From recent convergent findings in human neuroimaging, clinical epileptology, and experimental animal models, we make the case that the piriform cortex is likely to play a facilitating and amplifying role in human focal epileptogenesis, and may influence progression to epileptic intractability. PMID:25538678

Urinary Virome Perturbations in Kidney Transplantation.

PubMed

Sigdel, Tara K; Mercer, Neil; Nandoe, Sharvin; Nicora, Carrie D; Burnum-Johnson, Kristin; Qian, Wei-Jun; Sarwal, Minnie M

2018-01-01

The human microbiome is important for health and plays a role in essential metabolic functions and protection from certain pathogens. Conversely, dysbiosis of the microbiome is seen in the context of various diseases. Recent studies have highlighted that a complex microbial community containing hundreds of bacteria colonizes the healthy urinary tract, but little is known about the human urinary viruses in health and disease. To evaluate the human urinary virome in the context of kidney transplantation (tx), variations in the composition of the urinary virome were evaluated in urine samples from normal healthy volunteers as well as patients with kidney disease after they had undergone kidney tx. Liquid chromatography-mass spectrometry/mass spectrometry analysis was undertaken on a selected cohort of 142 kidney tx patients and normal healthy controls, from a larger biobank of 770 kidney biopsy matched urine samples. In addition to analysis of normal healthy control urine, the cohort of kidney tx patients had biopsy confirmed phenotype classification, coincident with the urine sample analyzed, of stable grafts (STA), acute rejection, BK virus nephritis, and chronic allograft nephropathy. We identified 37 unique viruses, 29 of which are being identified for the first time in human urine samples. The composition of the human urinary virome differs in health and kidney injury, and the distribution of viral proteins in the urinary tract may be further impacted by IS exposure, diet and environmental, dietary, or cutaneous exposure to various insecticides and pesticides.

Cascade of neural processing orchestrates cognitive control in human frontal cortex

PubMed Central

Tang, Hanlin; Yu, Hsiang-Yu; Chou, Chien-Chen; Crone, Nathan E; Madsen, Joseph R; Anderson, William S; Kreiman, Gabriel

2016-01-01

Rapid and flexible interpretation of conflicting sensory inputs in the context of current goals is a critical component of cognitive control that is orchestrated by frontal cortex. The relative roles of distinct subregions within frontal cortex are poorly understood. To examine the dynamics underlying cognitive control across frontal regions, we took advantage of the spatiotemporal resolution of intracranial recordings in epilepsy patients while subjects resolved color-word conflict. We observed differential activity preceding the behavioral responses to conflict trials throughout frontal cortex; this activity was correlated with behavioral reaction times. These signals emerged first in anterior cingulate cortex (ACC) before dorsolateral prefrontal cortex (dlPFC), followed by medial frontal cortex (mFC) and then by orbitofrontal cortex (OFC). These results disassociate the frontal subregions based on their dynamics, and suggest a temporal hierarchy for cognitive control in human cortex. DOI: http://dx.doi.org/10.7554/eLife.12352.001 PMID:26888070

Differentiation of muscarinic cholinergic receptor subtypes in human cortex and pons - Implications for anti-motion sickness therapy

NASA Technical Reports Server (NTRS)

Mccarthy, Bruce G.; Peroutka, Stephen J.

1988-01-01

Radioligand binding studies were used to analyze muscarinic cholinergic receptor subtypes in human cortex and pons. Muscarinic cholinergic receptors were labeled by H-3-quinuclidinyl benzilate (H-3-QNB). Scopolamine was equipotent in both brain regions and did not discriminate subtypes of H-3-QNB binding. By contrast, the M1 selective antagonist pirenzepine was approximately 33-fold more potent in human cortex than pons. Carbachol, a putative M2 selective agonist, was more than 100-fold more potent in human pons than cortex. These results demonstrate that the human pons contains a relatively large proportion of carbachol-sensitive muscarinic cholinergic receptors. Drugs targeted to this subpopulation of muscarinic cholinergic receptors may prove to be effective anti-motion sickness agents with less side effects than scopolamine.

Common medial frontal mechanisms of adaptive control in humans and rodents

PubMed Central

Frank, Michael J.; Laubach, Mark

2013-01-01

In this report, we describe how common brain networks within the medial frontal cortex facilitate adaptive behavioral control in rodents and humans. We demonstrate that low frequency oscillations below 12 Hz are dramatically modulated after errors in humans over mid-frontal cortex and in rats within prelimbic and anterior cingulate regions of medial frontal cortex. These oscillations were phase-locked between medial frontal cortex and motor areas in both rats and humans. In rats, single neurons that encoded prior behavioral outcomes were phase-coherent with low-frequency field oscillations particularly after errors. Inactivating medial frontal regions in rats led to impaired behavioral adjustments after errors, eliminated the differential expression of low frequency oscillations after errors, and increased low-frequency spike-field coupling within motor cortex. Our results describe a novel mechanism for behavioral adaptation via low-frequency oscillations and elucidate how medial frontal networks synchronize brain activity to guide performance. PMID:24141310

Characterization of organic osmolytes in avian renal medulla: a nonurea osmotic gradient system.

PubMed

Lien, Y H; Pacelli, M M; Braun, E J

1993-06-01

We measured the organic osmolytes present in the renal cortex and medullary cones of adult female domestic fowl before and after 48 h of water deprivation. Urine osmolality increased from 198 +/- 82 to 569 +/- 42 mosmol/kgH2O after water deprivation. In water-deprived birds, the major organic osmolytes, myoinositol, betaine, and taurine, in the medullary cones increased by 40, 100, and 24%, respectively, compared with control birds. No sorbitol was detected, and glycerophosphorylcholine (GPC) content was not affected by water deprivation. In the renal cortex, only betaine content increased significantly (4.8 +/- 0.6 vs. 3.1 +/- 0.3 mmol/kg wet wt) after water deprivation. In this study, we demonstrated that birds, like mammals, accumulate organic osmolytes in response to the increased interstitial osmolality that occurs during antidiuresis. Because urea is nearly absent in the avian medullary interstitium, our observation that GPC is not osmoregulated in the avian kidney supports the idea that GPC is the "counteracting osmolyte" for urea in the mammalian kidney. Furthermore, the organic osmolytes present in avian medullary cones are remarkably similar to those of the mammalian outer medulla. This similarity may be relevant to the morphological analogy of the two regions.

Surface Based Analysis of Diffusion Orientation for Identifying Architectonic Domains in the In Vivo Human Cortex

PubMed Central

McNab, Jennifer A.; Polimeni, Jonathan R.; Wang, Ruopeng; Augustinack, Jean C.; Fujimoto, Kyoko; Player, Allison; Janssens, Thomas; Farivar, Reza; Folkerth, Rebecca D.; Vanduffel, Wim; Wald, Lawrence L.

2012-01-01

Diffusion tensor MRI is sensitive to the coherent structure of brain tissue and is commonly used to study large-scale white matter structure. Diffusion in grey matter is more isotropic, however, several groups have observed coherent patterns of diffusion anisotropy within the cerebral cortical grey matter. We extend the study of cortical diffusion anisotropy by relating it to the local coordinate system of the folded cerebral cortex. We use 1mm and sub-millimeter isotropic resolution diffusion imaging to perform a laminar analysis of the principal diffusion orientation, fractional anisotropy, mean diffusivity and partial volume effects. Data from 6 in vivo human subjects, a fixed human brain specimen and an anesthetized macaque were examined. Large regions of cortex show a radial diffusion orientation. In vivo human and macaque data displayed a sharp transition from radial to tangential diffusion orientation at the border between primary motor and somatosensory cortex, and some evidence of tangential diffusion in secondary somatosensory cortex and primary auditory cortex. Ex vivo diffusion imaging in a human tissue sample showed some tangential diffusion orientation in S1 but mostly radial diffusion orientations in both M1 and S1. PMID:23247190

Biolasol: novel perfusion and preservation solution for kidneys.

PubMed

Cierpka, L; Ryszka, F; Dolińska, B; Smorąg, Z; Słomski, R; Wiaderkiewicz, R; Caban, A; Budziński, G; Oczkowicz, G; Wieczorek, J

2014-10-01

Biolasol solution (Pharmaceutical Research and Production Plant "Biochefa," Sosnowiec, Poland) is a novel extracellular perfusion and ex vivo hypothermic kidney preservation solution. It ensures maintenance of homeostasis, reduces tissue edema, has low viscosity, and allows the graft to preserve structural and functional integrity. It minimizes ischemia-reperfusion damage. Perfundates from control and transplanted kidneys flushed with Biolasol or ViaSpan solutions (Arkas, Warszawa, Poland) were analyzed. Parameters of serum and urine collected from 12 pigs after auto-transplantation were also analyzed. Renal medulla was investigated for structural alterations by analyzing hematoxylin and eosin-stained slides. The mean survival time of pigs after the auto-transplantation procedure was the measure for the novel Biolasol solution effectiveness. We observed a statistically significant decrease in marker enzyme levels alanine transaminase, aspartate transaminase, lactic dehydrogenase, and ions (Na and K) in pigs with grafts flushed with Biolasol. Histopathologic examination revealed that the renal cortex structure was not damaged after the use of Biolasol solution. Biolasol solution protects kidneys against ischemia damage and does not differ significantly from the "golden standard" ViaSpan solution.

Familial mixed nephrocalcinosis as a cause of chronic kidney failure: two case reports.

PubMed

de Arruda, Pedro Francisco Ferraz; Gatti, Márcio; de Arruda, José Germano Ferraz; Fácio, Fernando Nestor; Spessoto, Luis Cesar Fava; de Arruda, Laísa Ferraz; de Godoy, José Maria Pereira; Godoy, Moacir Fernandes

2014-10-27

Nephrocalcinosis consists of the deposition of calcium salts in the renal parenchyma and is considered the mixed form when it involves the renal cortex and medulla. The main etiological agents of this condition are primary hyperparathyroidism, renal tubular acidosis, medullary sponge kidney, hyperoxaluria and taking certain drugs. These factors can lead to hypercalcemia and/or hypercalciuria, which can give rise to nephrocalcinosis. Patient 1 was a 48-year-old Caucasian woman with a history of bilateral nephrocalcinosis causing chronic kidney failure. Imaging examinations (X-ray, ultrasound and computed tomography of the abdomen) revealed extensive calcium deposits in the renal parenchyma, indicating nephrocalcinosis as the causal factor of the disease. Patient 2 is the 45-year-old brother of patient 1. He exhibited an advanced stage of chronic kidney failure. As nephrocalcinosis is considered to have a genetic component, a family investigation revealed this condition in patient 2. Nephrocalcinosis may be detected incidentally through diagnostic imaging studies. Whenever possible, treatment should include the base disease that caused the appearance of the calcification, as the precise etiological determination is extremely important.

Studying Kidney Disease Using Tissue and Genome Engineering in Human Pluripotent Stem Cells.

PubMed

Garreta, Elena; González, Federico; Montserrat, Núria

2018-01-01

Kidney morphogenesis and patterning have been extensively studied in animal models such as the mouse and zebrafish. These seminal studies have been key to define the molecular mechanisms underlying this complex multistep process. Based on this knowledge, the last 3 years have witnessed the development of a cohort of protocols allowing efficient differentiation of human pluripotent stem cells (hPSCs) towards defined kidney progenitor populations using two-dimensional (2D) culture systems or through generating organoids. Kidney organoids are three-dimensional (3D) kidney-like tissues, which are able to partially recapitulate kidney structure and function in vitro. The current possibility to combine state-of-the art tissue engineering with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated systems 9 (Cas9)-mediated genome engineering provides an unprecedented opportunity for studying kidney disease with hPSCs. Recently, hPSCs with genetic mutations introduced through CRISPR/Cas9-mediated genome engineering have shown to produce kidney organoids able to recapitulate phenotypes of polycystic kidney disease and glomerulopathies. This mini review provides an overview of the most recent advances in differentiation of hPSCs into kidney lineages, and the latest implementation of the CRISPR/Cas9 technology in the organoid setting, as promising platforms to study human kidney development and disease. © 2017 S. Karger AG, Basel.

Ultrasonographic abdominal anatomy of healthy captive caracals (Caracal caracal).

PubMed

Makungu, Modesta; du Plessis, Wencke M; Barrows, Michelle; Koeppel, Katja N; Groenewald, Hermanus B

2012-09-01

Abdominal ultrasonography was performed in six adult captive caracals (Caracal caracal) to describe the normal abdominal ultrasonographic anatomy. Consistently, the splenic parenchyma was hyperechoic to the liver and kidneys. The relative echogenicity of the right kidney's cortex was inconsistent to the liver. The gall bladder was prominent in five animals and surrounded by a clearly visualized thin, smooth, regular echogenic wall. The wall thickness of the duodenum measured significantly greater compared with that of the jejunum and colon. The duodenum had a significantly thicker mucosal layer compared with that of the stomach. Such knowledge of the normal abdominal ultrasonographic anatomy of individual species is important for accurate diagnosis and interpretation of routine health examinations.

Lithium induces microcysts and polyuria in adolescent rat kidney independent of cyclooxygenase‐2

PubMed Central

Kjaersgaard, Gitte; Madsen, Kirsten; Marcussen, Niels; Jensen, Boye L.

2014-01-01

Abstract In patients, chronic treatment with lithium leads to renal microcysts and nephrogenic diabetes insipidus (NDI). It was hypothesized that renal cyclooxygenase‐2 (COX‐2) activity promotes microcyst formation and NDI. Kidney microcysts were induced in male adolescent rats by feeding dams with lithium (50 mmol/kg chow) from postnatal days 7–34. Lithium treatment induced somatic growth retardation, renal microcysts and dilatations in cortical collecting duct; it increased cortical cell proliferation and inactive pGSK‐3β abundance; it lowered aquaporin‐2 (AQP2) protein abundance and induced polyuria with decreased ability to concentrate the urine; and it increased COX‐2 protein level in thick ascending limb. Concomitant treatment with lithium and a specific COX‐2 inhibitor, parecoxib (5 mg/kg per day, P10–P34), did not prevent lithium‐induced microcysts and polyuria, but improved urine concentrating ability transiently after a 1‐desamino‐8‐D‐arginine vasopressin challenge. COX‐2 inhibition did not reduce cortical lithium‐induced cell proliferation and phosphorylation of glycogen synthase kinase‐3β (GSK‐3β). COX‐1 protein abundance increased in rat kidney cortex in response to lithium. COX‐1 immunoreactivity was found in microcyst epithelium in rat kidney. A human nephrectomy specimen from a patient treated for 28 years with lithium displayed multiple, COX‐1‐immunopositive, microcysts. In chronic lithium‐treated adolescent rats, COX‐2 is not colocalized with microcystic epithelium, mitotic activity, and inactive pGSK‐3β in collecting duct; a blocker of COX‐2 does not prevent cell proliferation, cyst formation, or GSK‐3β inactivation. It is concluded that COX‐2 activity is not the primary cause for microcysts and polyuria in a NaCl‐substituted rat model of lithium nephropathy. COX‐1 is a relevant candidate to affect the injured epithelium. PMID:24744881

Novel mechanism of regulation of the DNA repair enzyme OGG1 in tuberin-deficient cells

PubMed Central

Habib, Samy L.; Bhandari, Besant K.; Sadek, Nahed; Abboud-Werner, Sherry L.; Abboud, Hanna E.

2010-01-01

Tuberin (protein encodes by tuberous sclerosis complex 2, Tsc2) deficiency is associated with the decrease in the DNA repair enzyme 8-oxoG-DNA glycosylase (OGG1) in tumour kidney of tuberous sclerosis complex (TSC) patients. The purpose of this study was to elucidate the mechanisms by which tuberin regulates OGG1. The partial deficiency in tuberin expression that occurs in the renal proximal tubular cells and kidney cortex of the Eker rat is associated with decreased activator protein 4 (AP4) and OGG1 expression. A complete deficiency in tuberin is associated with loss of AP4 and OGG1 expression in kidney tumour from Eker rats and the accumulation of significant levels of 8-oxo-deoxyguanosine. Knockdown of tuberin expression in human renal epithelial cells (HEK293) with small interfering RNA (siRNA) also resulted in a marked decrease in the expression of AP4 and OGG1. In contrast, overexpression of tuberin in HEK293 cells increased the expression of AP4 and OGG1 proteins. Downregulation of AP4 expression using siRNA resulted in a significant decrease in the protein expression of OGG1. Immunoprecipitation studies show that AP4 is associated with tuberin in cells. Gel shift analysis and chromatin immunoprecipitation identified the transcription factor AP4 as a positive regulator of the OGG1 promoter. AP4 DNA-binding activity is significantly reduced in Tsc2−/− as compared with Tsc2+/+ cells. Transcriptional activity of the OGG1 promoter is also decreased in tuberin-null cells compared with wild-type cells. These data indicate a novel role for tuberin in the regulation of OGG1 through the transcription factor AP4. This regulation may be important in the pathogenesis of kidney tumours in patients with TSC disease. PMID:20837600

Long-term expression of glomerular genes in diabetic nephropathy.

PubMed

Chittka, Dominik; Banas, Bernhard; Lennartz, Laura; Putz, Franz Josef; Eidenschink, Kathrin; Beck, Sebastian; Stempfl, Thomas; Moehle, Christoph; Reichelt-Wurm, Simone; Banas, Miriam C

2018-01-11

Although diabetic nephropathy (DN) is the most common cause for end-stage renal disease in western societies, its pathogenesis still remains largely unclear. A different gene pattern of diabetic and healthy kidney cells is one of the probable explanations. Numerous signalling pathways have emerged as important pathophysiological mechanisms for diabetes-induced renal injury. Glomerular cells, as podocytes or mesangial cells, are predominantly involved in the development of diabetic renal lesions. While many gene assays concerning DN are performed with whole kidney or renal cortex tissue, we isolated glomeruli from black and tan, brachyuric (BTBR) obese/obese (ob/ob) and wildtype mice at four different timepoints (4, 8, 16 and 24 weeks) and performed an mRNA microarray to identify differentially expressed genes (DEGs). In contrast to many other diabetic mouse models, these homozygous ob/ob leptin-deficient mice develop not only a severe type 2 diabetes, but also diabetic kidney injury with all the clinical and especially histologic features defining human DN. By functional enrichment analysis we were able to investigate biological processes and pathways enriched by the DEGs at different disease stages. Altered expression of nine randomly selected genes was confirmed by quantitative polymerase chain reaction from glomerular RNA. Ob/ob type 2 diabetic mice showed up- and downregulation of genes primarily involved in metabolic processes and pathways, including glucose, lipid, fatty acid, retinol and amino acid metabolism. Members of the CYP4A and ApoB family were found among the top abundant genes. But more interestingly, altered gene loci showed enrichment for processes and pathways linked to angioneogenesis, complement cascades, semaphorin pathways, oxidation and reduction processes and renin secretion. The gene profile of BTBR ob/ob type 2 diabetic mice we conducted in this study can help to identify new key players in molecular pathogenesis of diabetic kidney injury. © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Assessing renal changes after remote ischemic preconditioning (RIPC) of the upper extremity using BOLD imaging at 3T.

PubMed

Siedek, Florian; Persigehl, Thorsten; Mueller, Roman-Ulrich; Burst, Volker; Benzing, Thomas; Maintz, David; Haneder, Stefan

2018-06-01

Acute kidney injury (AKI) is an important risk factor for a number of adverse outcomes including end-stage renal disease and cardiovascular morbidity and mortality. Whilst many clinical situations that can induce AKI are known-e.g. drug toxicity, contrast agent exposure or ischemia during surgery-targeted preventive or therapeutic measures are still lacking. As to renoprotective strategies, remote ischemic preconditioning (RIPC) is one of the most promising novel approaches and has been examined by a number of clinical trials. The aim of this study was to use blood oxygenation level-dependent (BOLD) MRI as a surrogate parameter to assess the effect of RIPC in healthy volunteers. In this IRB-approved, prospective study, 40 healthy volunteers were stratified with 20 undergoing an RIPC procedure (i.e. RIPC group) with a transient ischemia of the right arm, and 20 undergoing a sham procedure. Before and after the procedure, both kidneys of all participants were scanned using a 12-echo mGRE sequence for functional BOLD imaging at 3T. For each volunteer, 180 ROIs were placed in the cortex and the medulla of the kidneys. Ultimately, R2* values, which have an inverse correlation with the oxygenation level of tissue, were averaged for the RIPC and control groups. Following intervention, mean R2* values significantly decreased in the RIPC group in both the cortex (18.6 ± 2.3 vs. 17.5 ± 1.7 Hz; p = 0.0047) and medulla (34 ± 5.2 vs. 32.2 ± 4.2 Hz; p = 0.0001). However, no significant differences were observed in the control group. RIPC can be non-invasively assessed in healthy volunteers using BOLD MRI at 3T, demonstrating a higher oxygen content in kidney tissue. This study presents a first-in-man trial establishing a quantifiable readout of RIPC and its effects on kidney physiology. BOLD measurements may advance clinical trials in further evaluating RIPC for future clinical care.

Interleukin-1β Activates a MYC-Dependent Metabolic Switch in Kidney Stromal Cells Necessary for Progressive Tubulointerstitial Fibrosis.

PubMed

Lemos, Dario R; McMurdo, Michael; Karaca, Gamze; Wilflingseder, Julia; Leaf, Irina A; Gupta, Navin; Miyoshi, Tomoya; Susa, Koichiro; Johnson, Bryce G; Soliman, Kirolous; Wang, Guanghai; Morizane, Ryuji; Bonventre, Joseph V; Duffield, Jeremy S

2018-06-01

Background Kidney injury is characterized by persisting inflammation and fibrosis, yet mechanisms by which inflammatory signals drive fibrogenesis remain poorly defined. Methods RNA sequencing of fibrotic kidneys from patients with CKD identified a metabolic gene signature comprising loss of mitochondrial and oxidative phosphorylation gene expression with a concomitant increase in regulators and enzymes of glycolysis under the control of PGC1 α and MYC transcription factors, respectively. We modeled this metabolic switch in vivo , in experimental murine models of kidney injury, and in vitro in human kidney stromal cells (SCs) and human kidney organoids. Results In mice, MYC and the target genes thereof became activated in resident SCs early after kidney injury, suggesting that acute innate immune signals regulate this transcriptional switch. In vitro , stimulation of purified human kidney SCs and human kidney organoids with IL-1 β recapitulated the molecular events observed in vivo , inducing functional metabolic derangement characterized by increased MYC-dependent glycolysis, the latter proving necessary to drive proliferation and matrix production. MYC interacted directly with sequestosome 1/p62, which is involved in proteasomal degradation, and modulation of p62 expression caused inverse effects on MYC expression. IL-1 β stimulated autophagy flux, causing degradation of p62 and accumulation of MYC. Inhibition of the IL-1R signal transducer kinase IRAK4 in vivo or inhibition of MYC in vivo as well as in human kidney organoids in vitro abrogated fibrosis and reduced tubular injury. Conclusions Our findings define a connection between IL-1 β and metabolic switch in fibrosis initiation and progression and highlight IL-1 β and MYC as potential therapeutic targets in tubulointerstitial diseases. Copyright © 2018 by the American Society of Nephrology.

Human Alpha Defensin 5 Expression in the Human Kidney and Urinary Tract

PubMed Central

Porter, Edith; Bevins, Charles L.; DiRosario, Julianne; Becknell, Brian; Wang, Huanyu

2012-01-01

Background The mechanisms that maintain sterility in the urinary tract are incompletely understood. Recent studies have implicated the importance of antimicrobial peptides (AMP) in protecting the urinary tract from infection. Here, we characterize the expression and relevance of the AMP human alpha-defensin 5 (HD5) in the human kidney and urinary tract in normal and infected subjects. Methodology/Principal Findings Using RNA isolated from human kidney, ureter, and bladder tissue, we performed quantitative real-time PCR to show that DEFA5, the gene encoding HD5, is constitutively expressed throughout the urinary tract. With pyelonephritis, DEFA5 expression significantly increased in the kidney. Using immunoblot analysis, HD5 production also increased with pyelonephritis. Immunostaining localized HD5 to the urothelium of the bladder and ureter. In the kidney, HD5 was primarily produced in the distal nephron and collecting tubules. Using immunoblot and ELISA assays, HD5 was not routinely detected in non-infected human urine samples while mean urinary HD5 production increased with E.coli urinary tract infection. Conclusions/Significance DEFA5 is expressed throughout the urinary tract in non-infected subjects. Specifically, HD5 is expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney. With infection, HD5 expression increases in the kidney and levels become detectable in the urine. To our knowledge, our findings represent the first to quantitate HD5 expression and production in the human kidney. Moreover, this is the first report to detect the presence of HD5 in infected urine samples. Our results suggest that HD5 may have an important role in maintaining urinary tract sterility. PMID:22359618

Interhemispheric gene expression differences in the cerebral cortex of humans and macaque monkeys.

PubMed

Muntané, Gerard; Santpere, Gabriel; Verendeev, Andrey; Seeley, William W; Jacobs, Bob; Hopkins, William D; Navarro, Arcadi; Sherwood, Chet C

2017-09-01

Handedness and language are two well-studied examples of asymmetrical brain function in humans. Approximately 90% of humans exhibit a right-hand preference, and the vast majority shows left-hemisphere dominance for language function. Although genetic models of human handedness and language have been proposed, the actual gene expression differences between cerebral hemispheres in humans remain to be fully defined. In the present study, gene expression profiles were examined in both hemispheres of three cortical regions involved in handedness and language in humans and their homologues in rhesus macaques: ventrolateral prefrontal cortex, posterior superior temporal cortex (STC), and primary motor cortex. Although the overall pattern of gene expression was very similar between hemispheres in both humans and macaques, weighted gene correlation network analysis revealed gene co-expression modules associated with hemisphere, which are different among the three cortical regions examined. Notably, a receptor-enriched gene module in STC was particularly associated with hemisphere and showed different expression levels between hemispheres only in humans.

The multisensory function of the human primary visual cortex.

PubMed

Murray, Micah M; Thelen, Antonia; Thut, Gregor; Romei, Vincenzo; Martuzzi, Roberto; Matusz, Pawel J

2016-03-01

It has been nearly 10 years since Ghazanfar and Schroeder (2006) proposed that the neocortex is essentially multisensory in nature. However, it is only recently that sufficient and hard evidence that supports this proposal has accrued. We review evidence that activity within the human primary visual cortex plays an active role in multisensory processes and directly impacts behavioural outcome. This evidence emerges from a full pallet of human brain imaging and brain mapping methods with which multisensory processes are quantitatively assessed by taking advantage of particular strengths of each technique as well as advances in signal analyses. Several general conclusions about multisensory processes in primary visual cortex of humans are supported relatively solidly. First, haemodynamic methods (fMRI/PET) show that there is both convergence and integration occurring within primary visual cortex. Second, primary visual cortex is involved in multisensory processes during early post-stimulus stages (as revealed by EEG/ERP/ERFs as well as TMS). Third, multisensory effects in primary visual cortex directly impact behaviour and perception, as revealed by correlational (EEG/ERPs/ERFs) as well as more causal measures (TMS/tACS). While the provocative claim of Ghazanfar and Schroeder (2006) that the whole of neocortex is multisensory in function has yet to be demonstrated, this can now be considered established in the case of the human primary visual cortex. Copyright © 2015 Elsevier Ltd. All rights reserved.

[The history of kidney transplantation].

PubMed

Hatzinger, M; Stastny, M; Grützmacher, P; Sohn, M

2016-10-01

The history of kidney transplantation is a history of many unsuccessful efforts and setbacks, but also the history of perseverance, pioneering spirit, and steadfast courage. The first successful transplantation of a dog kidney was done by the Austrian Emerich Ullmann (1861-1937) in 1902. The kidney was connected to the carotid artery of the dog and the ureter ended freely. The organ produced urine for a couple of days before it died. In 1909, there were efforts to transplant human kidneys from deceased patients to monkeys and in the following year the first xenotransplantation in humans was completed. Different kinds of donors were tried: dogs, monkeys, goats and lambs, all without success. In 1939, the first transplantation from a deceased human donor was done by the Russion Yurii Voronoy, the patient survived for only a couple of days, and the organ never worked. In 1953, the first temporarily successful transplantation of a human kidney was performed by Jean Hamburger in Paris. A 16-year-old boy received the kidney of his mother as living donor transplantation. Then in 1954, a milestone was made with the first long-term successful kidney transplantation by Joseph Murray: the transplantation was done between monozygotic twins; the organ survived for 8 years. For his efforts in kidney transplantation, Murray was honored with the Nobel Prize in medicine in 1990. In 1962, the first kidney transplantation between genetically nonrelated patients was done using immunosuppression and in 1963 the first kidney transplantation in Germany was done by Reinhard Nagel and Wilhelm Brosig in Berlin. The aim of this article is to present the history of kidney transplantation from the beginning until today.

Hippocampus, Perirhinal Cortex, and Complex Visual Discriminations in Rats and Humans

ERIC Educational Resources Information Center

Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.; Squire, Larry R.; Clark, Robert E.

2015-01-01

Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with…

CCR2-dependent Gr1high monocytes promote kidney injury in shiga toxin-induced hemolytic uremic syndrome in mice.

PubMed

Pohl, Judith-Mira; Volke, Julia K; Thiebes, Stephanie; Brenzel, Alexandra; Fuchs, Kerstin; Beziere, Nicolas; Ehrlichmann, Walter; Pichler, Bernd J; Squire, Anthony; Gueler, Faikah; Engel, Daniel R

2018-06-01

The hemolytic uremic syndrome (HUS) is a life-threatening disease of the kidney that is induced by shiga toxin-producing E.coli. Major changes in the monocytic compartment and in CCR2-binding chemokines have been observed. However, the specific contribution of CCR2-dependent Gr1 high monocytes is unknown. To investigate the impact of these monocytes during HUS, we injected a combination of LPS and shiga toxin into mice. We observed an impaired kidney function and elevated levels of the CCR2-binding chemokine CCL2 after shiga toxin/LPS- injection, thus suggesting Gr1 high monocyte infiltration into the kidney. Indeed, the number of Gr1 high monocytes was strongly increased one day after HUS induction. Moreover, these cells expressed high levels of CD11b suggesting activation after tissue entry. Non-invasive PET-MR imaging revealed kidney injury mainly in the kidney cortex and this damage coincided with the detection of Gr1 high monocytes. Lack of Gr1 high monocytes in Ccr2-deficient animals reduced neutrophil gelatinase-associated lipocalin and blood urea nitrogen levels. Moreover, the survival of Ccr2-deficient animals was significantly improved. Conclusively, this study demonstrates that CCR2-dependent Gr1 high monocytes contribute to the kidney injury during HUS and targeting these cells is beneficial during this disease. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Clinical Significance of Persistent Global and Focal Computed Tomography Nephrograms After Cardiac Catheterization and Their Relationships to Urinary Biomarkers of Kidney Damage and Procedural Factors: Pilot Study.

PubMed

Chu, Lisa L; Katzberg, Richard W; Solomon, Richard; Southard, Jeffrey; Evans, Scott J; Li, Chin-Shang; McDonald, Jennifer S; Payne, Catherine; Boone, John M; RamachandraRao, Satish P

2016-12-01

We evaluate the relationships between persistent computed tomography (CT) nephrograms and acute kidney injury after cardiac catheterization (CC). We compare changes in urinary biomarkers kidney injury molecule 1 (KIM-1), cystatin C, and serum creatinine to procedural factors. From 159 eligible patients without renal insufficiency (estimated glomerular filtration rate >60 mL/min), 40 random patients (age range, 42-81 years; mean age, 64 years; 25 men, 15 women) gave written informed consent to undergo unenhanced CT limited to their kidneys 24 hours after CC. Semiquantitative assessment for global nephrograms and quantitative assessment of focal nephrograms in each kidney was performed. Computed tomography attenuation (Hounsfield units) of the renal cortex was measured. Serum creatinine, KIM-1, and cystatin C were measured before and 24 hours after CC. Robust linear regression showed that both relative changes in KIM-1 and cystatin C had positive relationships with kidney CT attenuation (P = 0.012 and 0.002, respectively). Spearman rank correlation coefficient showed that both absolute changes and relative changes in KIM-1 and cystatin C had positive correlations with global nephrogram grades (P = 0.025 and 0.040, respectively, for KIM-1; P = 0.013 and 0.019, respectively, for cystatin C). Global nephrograms on unenhanced CT in patients who have undergone CC are significantly correlated with changes in urinary biomarkers for kidney damage.

Simultaneous evaluation of renal morphology and function in live kidney donors using dynamic magnetic resonance imaging.

PubMed

Artunc, F; Yildiz, S; Rossi, C; Boss, A; Dittmann, H; Schlemmer, H P; Risler, T; Heyne, N

2010-06-01

Evaluation of potential kidney donors requires the assessment of both kidney anatomy and function. In this prospective study, we sought to expand the diagnostic yield of magnetic resonance (MR) by adding functional measurements of glomerular filtration rate (GFR) and split renal function. Between 2007 and 2009, all potential kidney donors presenting to our facility underwent a comprehensive single-stop MR study that included an assessment of anatomy, angiography and functional measurements. GFR was measured after a bolus injection of gadobutrol (4 ml, approximately 0.05 mmol/kg) and calculated from the washout of the signal intensity obtained over the liver. Split renal function was calculated from the increase of signal intensity over the renal cortex. Values were compared to renal scintigraphy with (99m)Tc-DTPA from the same day. The MR investigation was successfully performed in 21 participants. The GFR derived from MR (MR-GFR) correlated well (r = 0.84) with the GFR derived from scintigraphy (DTPA-GFR). The mean value of the paired differences was 4 +/- 13 [SD] ml/min/1.73 m(2) and was not significantly different from zero. The ratio between right and left kidney function was similar with both techniques (1.01 +/- 0.17 with MR and 1.06 +/- 0.12 with scintigraphy, P = 0.20). We demonstrate an MR-based approach to comprehensively evaluate both kidney anatomy and function in a single investigation, thereby facilitating the evaluation of potential kidney donors.

Establishment of donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion

DTIC Science & Technology

2017-09-01

the ideal solution. Combined mixed allogeneic chimerism induction and kidney transplantation has been shown to induce robust tolerance to the kidney ...induction to kidney allografts in non-human primates and humans despite the transience of donor chimerism. However, evidence indicates that durable mixed...chimerism may be required for tolerance induction to tissues or organs other than kidney . Amnion-derived multipotent progenitor (AMP) cells possess

pH imaging of mouse kidneys in vivo using a frequency-dependent paraCEST agent.

PubMed

Wu, Yunkou; Zhang, Shanrong; Soesbe, Todd C; Yu, Jing; Vinogradov, Elena; Lenkinski, Robert E; Sherry, A Dean

2016-06-01

This study explored the feasibility of using a pH responsive paramagnetic chemical exchange saturation transfer (paraCEST) agent to image the pH gradient in kidneys of healthy mice. CEST signals were acquired on an Agilent 9.4 Tesla small animal MRI system using a steady-state gradient echo pulse sequence after a bolus injection of agent. The magnetic field inhomogeneity across each kidney was corrected using the WASSR method and pH maps were calculated by measuring the frequency of water exchange signal arising from the agent. Dynamic CEST studies demonstrated that the agent was readily detectable in kidneys only between 4 to 12 min postinjection. The CEST images showed a higher signal intensity in the pelvis and calyx regions and lower signal intensity in the medulla and cortex regions. The pH maps reflected tissue pH values spanning from 6.0 to 7.5 in kidneys of healthy mice. This study demonstrated that pH maps of the kidney can be imaged in vivo by measuring the pH-dependent chemical shift of a single water exchange CEST peak without prior knowledge of the agent concentration in vivo. The results demonstrate the potential of using a simple frequency-dependent paraCEST agent for mapping tissue pH in vivo. Magn Reson Med 75:2432-2441, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Zinc deficiency during growth: influence on renal function and morphology.

PubMed

Tomat, Analía Lorena; Costa, María Angeles; Girgulsky, Luciana Carolina; Veiras, Luciana; Weisstaub, Adriana Ruth; Inserra, Felipe; Balaszczuk, Ana María; Arranz, Cristina Teresa

2007-03-13

This study was designed to investigate the effects of moderate zinc deficiency during growth on renal morphology and function in adult life. Weaned male Wistar rats were divided into two groups and fed either a moderately zinc-deficient diet (zinc: 8 mg/kg, n=12) or a control diet (zinc: 30 mg/kg, n=12) for 60 days. We evaluated: renal parameters, NADPH-diaphorase and nitric oxide synthase activity in kidney, renal morphology and apoptotic cells in renal cortex. Zinc-deficient rats showed a decrease in glomerular filtration rate and no changes in sodium and potassium urinary excretion. Zinc deficiency decreased NADPH diaphorase activity in glomeruli and tubular segment of nephrons, and reduced activity of nitric oxide synthase in the renal medulla and cortex, showing that zinc plays an important role in preservation of the renal nitric oxide system. A reduction in nephron number, glomerular capillary area and number of glomerular nuclei in cortical and juxtamedullary areas was observed in zinc deficient kidneys. Sirius red staining and immunostaining for alpha-smooth muscle-actin and collagen III showed no signs of fibrosis in the renal cortex and medulla. An increase in the number of apoptotic cells in distal tubules and cortical collecting ducts neighboring glomeruli and, to a lesser extent, in the glomeruli was observed in zinc deficient rats. The major finding of our study is the emergence of moderate zinc deficiency during growth as a potential nutritional factor related to abnormalities in renal morphology and function that facilitates the development of cardiovascular and renal diseases in adult life.

The preferential accumulation of heavy metals in different tissues following frequent respiratory exposure to PM2.5 in rats

PubMed Central

Li, Qingzhao; Liu, Huibin; Alattar, Mohamed; Jiang, Shoufang; Han, Jing; Ma, Yujiao; Jiang, Chunyang

2015-01-01

This study aimed to explore the pattern of accumulation of some of main heavy metals in blood and various organs of rats after exposed to the atmospheric fine particulate matter (PM2.5). Rats were randomly divided into control and three treatment groups (tracheal perfusion with 10 mg/kg, 20 mg/kg and 40 mg/kg of PM2.5 suspension liquid, respectively). Whole blood and the lung, liver, kidney, and cerebral cortex were harvested after rats were treated and sacrificed. The used heavy metals were detected using inductively coupled plasma-mass spectrometry (ICP-MS) instrument. As results, Lead was increased in the liver, lung and cerebral cortex and the level of manganese was significantly elevated in the liver and cerebral cortex in PM2.5 treated rats. Besides, arsenic was prominently enriched both in cerebral cortex and in blood, and so did the aluminum in the cerebral cortex and the copper in the liver. However, cadmium, chromium and nickel have shown no difference between the control group and the three PM2.5 treated groups. Following the exposure of PM2.5, different heavy metals are preferentially accumulated in different body tissues. PMID:26582271

Successful Dual Kidney Transplantation After Hypothermic Oxygenated Perfusion of Discarded Human Kidneys

PubMed Central

Ravaioli, Matteo; De Pace, Vanessa; Comai, Giorgia; Busutti, Marco; Gaudio, Massimo Del; Amaduzzi, Annalisa; Cucchetti, Alessandro; Siniscalchi, Antonio; La Manna, Gaetano; D’Errico, Antonietta A.D.; Pinna, Antonio Daniele

2017-01-01

Patient: Female, 58 Final Diagnosis: Nephroangiosclerosis Symptoms: Renal failure Medication: — Clinical Procedure: Resuscitation of grafts by hypothermic oxygenated perfusion Specialty: Transplantology Objective: Challenging differential diagnosis Background: The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). Case Report: Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate’s lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. Conclusions: HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys. PMID:28928357

Prediabetic nephropathy as an early consequence of the high-calorie/high-fat diet: relation to oxidative stress.

PubMed

Shevalye, Hanna; Lupachyk, Sergey; Watcho, Pierre; Stavniichuk, Roman; Khazim, Khaled; Abboud, Hanna E; Obrosova, Irina G

2012-03-01

This study evaluated early renal functional, structural, and biochemical changes in high-calorie/high-fat diet fed mice, a model of prediabetes and alimentary obesity. Male C57BL6/J mice were fed normal (11 kcal% fat) or high-fat (58 kcal% fat) diets for 16 wk. Renal changes were evaluated by histochemistry and immunohistochemistry, Western blot analysis, ELISA, enzymatic assays, and chemiluminometry. High-fat diet consumption led to increased body and kidney weights, impaired glucose tolerance, hyperinsulinemia, polyuria, a 2.7-fold increase in 24-h urinary albumin excretion, 20% increase in renal glomerular volume, 18% increase in renal collagen deposition, and 8% drop of glomerular podocytes. It also resulted in a 5.3-fold increase in urinary 8-isoprostane excretion and a 38% increase in renal cortex 4-hydroxynonenal adduct accumulation. 4-hydroxynonenal adduct level and immunoreactivity or Sirtuin 1 expression in renal medulla were not affected. Studies of potential mechanisms of the high-fat diet induced renal cortex oxidative injury revealed that whereas nicotinamide adenine dinucleotide phosphate reduced form oxidase activity only tended to increase, 12/15-lipoxygenase was significantly up-regulated, with approximately 12% increase in the enzyme protein expression and approximately 2-fold accumulation of 12(S)-hydroxyeicosatetraenoic acid, a marker of 12/15-lipoxygenase activity. Accumulation of periodic acid-Schiff -positive material, concentrations of TGF-β, sorbitol pathway intermediates, and expression of nephrin, CAAT/enhancer-binding protein homologous protein, phosphoeukaryotic initiation factor-α, and total eukaryotic initiation factor-α in the renal cortex were indistinguishable between experimental groups. Vascular endothelial growth factor concentrations were reduced in high-fat diet fed mice. In conclusion, systemic and renal cortex oxidative stress associated with 12/15-lipoxygenase overexpression and activation is an early phenomenon caused by high-calorie/high-fat diet consumption and a likely contributor to kidney disease associated with prediabetes and alimentary obesity.

Constraint, consent, and well-being in human kidney sales.

PubMed

Hughes, Paul M

2009-12-01

This paper canvasses recent arguments in favor of commercial markets in human transplant kidneys, raising objections to those arguments on grounds of the role of injustice, exploitation, and coercion in compromising the autonomy of those most likely to sell a kidney, namely, the least well off members of society.

Cellular and subcellular localization of uncoupling protein 2 in the human kidney.

PubMed

Nigro, Michelangelo; De Sanctis, Claudia; Formisano, Pietro; Stanzione, Rosita; Forte, Maurizio; Capasso, Giovambattista; Gigliotti, Giuseppe; Rubattu, Speranza; Viggiano, Davide

2018-06-23

The uncoupling protein-2 (UCP2) is an anion transporter that plays a key role in the control of intracellular oxidative stress. In animal models UCP2 downregulation has several pathological sequelae, particularly affecting the vasculature and the kidney. Specifically, in these models kidney damage is highly favored in the absence of UCP2 in the context of experimental hypertension. Confirmations of these data in humans awaits further information, as no data are yet available concerning the cell-type and subcellular expression in the human kidney. In the present study, we aimed to characterize the UCP2 protein distribution in human kidney biopsies. In humans UCP2 is mainly localized in proximal convoluted tubule cells, with an intracytoplasmic punctate staining. UCP2 positive puncta are often localized at the interface between the endoplasmic reticulum and the mitochondria. Glomerular structures do not express UCP2 at detectable levels. The expression of UCP2 in proximal tubular cells may explain their relative propensity to damage in pathological conditions including the hypertensive disease.

Pharmacological evaluation of [123I]-CLINDE: a radioiodinated imidazopyridine-3-acetamide for the study of peripheral benzodiazepine binding sites (PBBS).

PubMed

Mattner, Filomena; Mardon, Karine; Katsifis, Andrew

2008-04-01

The study aims to evaluate the iodinated imidazopyridine, N',N'-diethyl-6-Chloro-(4'-[(123)I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide ([(123)I]-CLINDE) as a tracer for the study of peripheral benzodiazepine binding sites (PBBS). In vitro studies were performed using membrane homogenates and sections from kidney, adrenals, and brain cortex of Sprague-Dawley (SD) rats and incubated with [(123)I]-CLINDE. For in vivo studies, the rats were injected with [(123)I]-CLINDE. In competition studies, PBBS-specific drugs PK11195 and Ro 5-4864 and the CBR specific drug Flumazenil were injected before the radiotracer. In vitro binding studies in adrenal, kidney, and cortex mitochondrial membranes indicated that [(123)I]-CLINDE binds with high affinity to PBBS, K(d) = 12.6, 0.20, and 3.84 nM, respectively. The density of binding sites was 163, 5.3, and 0.34 pmol/mg protein, respectively. In vivo biodistribution indicated high uptake in adrenals (5.4), heart (1.5), lungs (1.5), kidney (1.5) %ID/g at 6 h p.i. In the central nervous system (CNS), the olfactory bulbs displayed the highest uptake; up to six times the activity in blood. Pre-administration of unlabeled CLINDE, PK11195 and Ro 5-4864 (1 mg/kg) reduced the uptake of [(123)I]-CLINDE by 70-55% in olfactory bulbs. In the kidney and heart, a reduction of 60-80% ID/g was observed, while an increase was observed in the adrenals requiring 10 mg/kg for significant displacement. Flumazenil had no effect on uptake in peripheral organs and brain. Metabolite analysis indicated >90% of the radioactivity in the above tissues was intact [(123)I]-CLINDE. [(123)I]-CLINDE displays high and selective uptake for the PBBS and warrants further development as a probe for imaging PBBS using single photon emission computed tomography (SPECT).

Inhibitory interneurons of the human prefrontal cortex display conserved evolution of the phenotype and related genes.

PubMed

Sherwood, Chet C; Raghanti, Mary Ann; Stimpson, Cheryl D; Spocter, Muhammad A; Uddin, Monica; Boddy, Amy M; Wildman, Derek E; Bonar, Christopher J; Lewandowski, Albert H; Phillips, Kimberley A; Erwin, Joseph M; Hof, Patrick R

2010-04-07

Inhibitory interneurons participate in local processing circuits, playing a central role in executive cognitive functions of the prefrontal cortex. Although humans differ from other primates in a number of cognitive domains, it is not currently known whether the interneuron system has changed in the course of primate evolution leading to our species. In this study, we examined the distribution of different interneuron subtypes in the prefrontal cortex of anthropoid primates as revealed by immunohistochemistry against the calcium-binding proteins calbindin, calretinin and parvalbumin. In addition, we tested whether genes involved in the specification, differentiation and migration of interneurons show evidence of positive selection in the evolution of humans. Our findings demonstrate that cellular distributions of interneuron subtypes in human prefrontal cortex are similar to other anthropoid primates and can be explained by general scaling rules. Furthermore, genes underlying interneuron development are highly conserved at the amino acid level in primate evolution. Taken together, these results suggest that the prefrontal cortex in humans retains a similar inhibitory circuitry to that in closely related primates, even though it performs functional operations that are unique to our species. Thus, it is likely that other significant modifications to the connectivity and molecular biology of the prefrontal cortex were overlaid on this conserved interneuron architecture in the course of human evolution.

Functionally Specific Oscillatory Activity Correlates between Visual and Auditory Cortex in the Blind

ERIC Educational Resources Information Center

Schepers, Inga M.; Hipp, Joerg F.; Schneider, Till R.; Roder, Brigitte; Engel, Andreas K.

2012-01-01

Many studies have shown that the visual cortex of blind humans is activated in non-visual tasks. However, the electrophysiological signals underlying this cross-modal plasticity are largely unknown. Here, we characterize the neuronal population activity in the visual and auditory cortex of congenitally blind humans and sighted controls in a…

Methylphenidate clinically oral doses improved brain and heart glutathione redox status and evoked renal and cardiac tissue injury in rats.

PubMed

Loureiro-Vieira, Sara; Costa, Vera Marisa; Duarte, José Alberto; Duarte-Araújo, Margarida; Gonçalves-Monteiro, Salomé; Maria de Lourdes, Bastos; Carvalho, Félix; Capela, João Paulo

2018-04-01

Methylphenidate (MPH) is a first-line stimulant drug to treat attention deficit hyperactivity disorder (ADHD). Overdiagnosis of ADHD and MPH abuse lead to serious concerns about the possible long-term adverse consequences of MPH in healthy children and adolescents. We aimed to evaluate MPH effects in adolescent male Wistar rats (postnatal day 40) using an oral dose scheme (2 daily MPH doses 5 mg/kg in a 5% sucrose solution, 5 h apart, for 7 days) that mimics the therapeutic doses given to human adolescents. Twenty-four hours after the last MPH administration, rats were sacrificed and brain areas [cerebellum, prefrontal cortex (PFC), hippocampus, and striatum], peripheral organs (liver, heart, and kidneys), and blood were collected for biochemical and histological analysis. MPH treatment did not alter rats' body temperature or weight, neither food or water intake throughout the experiment. The ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) significantly increased in the PFC and hippocampus of MPH-treated rats, meanwhile protein carbonylation remained unchanged in the brain. In the heart, the GSH/GSSG ratio and GSH levels were significantly increased, with decreased GSSG, while histology revealed significant damage, namely interstitial edema, vascular congestion, and presence of a fibrin-like material in the interstitial space. In the kidneys, MPH treatment resulted in extensive necrotic areas with cellular disorganization and cell infiltration, and immunohistochemistry analysis revealed a marked activation of nuclear factor-ĸB. This study showed that clinically relevant oral MPH doses improve the GSH redox status in the brain and heart, but evoke heart and kidney tissue damage to adolescent rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Mangiferin attenuates renal fibrosis through down-regulation of osteopontin in diabetic rats.

PubMed

Zhu, Xia; Cheng, Ya-Qin; Du, Lei; Li, Yu; Zhang, Fan; Guo, Hao; Liu, Yao-Wu; Yin, Xiao-Xing

2015-02-01

This study was designed to investigate the effects of mangiferin on renal fibrosis, osteopontin production, and inflammation in the kidney of diabetic rats. Diabetes was induced through the single administration of streptozotocin (55 mg/kg, i.p.). Diabetic rats were treated with mangiferin (15, 30, and 60 mg/kg/day, i.g.) for 9 weeks. The kidney was fixed in 10% formalin for glomerulus fibrosis examination using Masson trichrome staining. Kidney and blood were obtained for assays of the associated biochemical parameters. Chronic mangiferin treatment prevented renal glomerulus fibrosis evidenced by decreases in Mason-stained positive area of glomeruli, protein expression of type IV collagen, and α-smooth muscle actin in the kidney of diabetic rats, in comparison with decreases in mRNA and protein expression of osteopontin as well as protein expression of cyclooxygenase 2 and NF-кB p65 subunit in the renal cortex of diabetic rats. Moreover, mangiferin reduced the levels of interleukin 1β in both the serum and the kidney of diabetic rats. Our findings demonstrate that mangiferin prevents the renal glomerulus fibrosis of diabetic rats, which is realized through the suppression of osteopontin overproduction and inflammation likely via inactivation of NF-кB. Copyright © 2014 John Wiley & Sons, Ltd.

Neurogranin binds α-synuclein in the human superior temporal cortex and interaction is decreased in Parkinson's disease.

PubMed

Koob, Andrew O; Shaked, Gideon M; Bender, Andreas; Bisquertt, Alejandro; Rockenstein, Edward; Masliah, Eliezer

2014-12-03

Neurogranin is a calmodulin binding protein that has been implicated in learning and memory, long-term potentiation and synaptic plasticity. Neurons expressing neurogranin in the cortex degenerate in late stages of Parkinson's disease with widespread α-synuclein pathology. While analyzing neurogranin gene expression levels through rtPCR in brains of mouse models overexpressing human α-synuclein, we found levels were elevated 2.5 times when compared to nontransgenic animals. Immunohistochemistry in the cortex revealed colocalization between α-synuclein and neurogranin in mouse transgenics when compared to control mice. Coimmunoprecipitation studies in the superior temporal cortex in humans confirmed interaction between α-synuclein and neurogranin, and decreased interaction between α-synuclein and neurogranin was noticed in patients diagnosed with Parkinson's disease when compared to normal control brains. Additionally, phosphorylated neurogranin levels were also decreased in the human superior temporal cortex in patients diagnosed with Parkinson's disease and patients diagnosed with dementia with Lewy bodies. Here, we show for the first time that neurogranin binds to α-synuclein in the human cortex, and this interaction decreases in Parkinson's disease along with the phosphorylation of neurogranin, a molecular process thought to be involved in learning and memory. Copyright © 2014 Elsevier B.V. All rights reserved.

Neurogranin binds α-synuclein in the human superior temporal cortex and interaction is decreased in Parkinson’s disease

PubMed Central

Koob, Andrew O.; Shaked, Gideon M.; Bender, Andreas; Bisquertt, Alejandro; Rockenstein, Edward; Masliah, Eliezer

2016-01-01

Neurogranin is a calmodulin binding protein that has been implicated in learning and memory, long-term potentiation and synaptic plasticity. Neurons expressing neurogranin in the cortex degenerate in late stages of Parkinson’s disease with widespread α-synuclein pathology. While analyzing neurogranin gene expression levels through rtPCR in brains of mouse models overexpressing human α-synuclein, we found levels were elevated 2.5 times when compared to nontransgenic animals. Immunohistochemistry in the cortex revealed colocalization between α-synuclein and neurogranin in mouse transgenics when compared to control mice. Coimmunoprecipitation studies in the superior temporal cortex in humans confirmed interaction between α-synuclein and neurogranin, and decreased interaction between α-synuclein and neurogranin was noticed in patients diagnosed with Parkinson’s disease when compared to normal control brains. Additionally, phosphorylated neurogranin levels were also decreased in the human superior temporal cortex in patients diagnosed with Parkinson’s disease and patients diagnosed with dementia with Lewy bodies. Here, we show for the first time that neurogranin binds to α-synuclein in the human cortex, and this interaction decreases in Parkinson’s disease along with the phosphorylation of neurogranin, a molecular process thought to be involved in learning and memory. PMID:25446004

Connectivity-based parcellation of human cingulate cortex and its relation to functional specialization.

PubMed

Beckmann, Matthias; Johansen-Berg, Heidi; Rushworth, Matthew F S

2009-01-28

Whole-brain neuroimaging studies have demonstrated regional variations in function within human cingulate cortex. At the same time, regional variations in cingulate anatomical connections have been found in animal models. It has, however, been difficult to estimate the relationship between connectivity and function throughout the whole cingulate cortex within the human brain. In this study, magnetic resonance diffusion tractography was used to investigate cingulate probabilistic connectivity in the human brain with two approaches. First, an algorithm was used to search for regional variations in the probabilistic connectivity profiles of all cingulate cortex voxels with the whole of the rest of the brain. Nine subregions with distinctive connectivity profiles were identified. It was possible to characterize several distinct areas in the dorsal cingulate sulcal region. Several distinct regions were also found in subgenual and perigenual cortex. Second, the probabilities of connection between cingulate cortex and 11 predefined target regions of interest were calculated. Cingulate voxels with a high probability of connection with the different targets formed separate clusters within cingulate cortex. Distinct connectivity fingerprints characterized the likelihood of connections between the extracingulate target regions and the nine cingulate subregions. Last, a meta-analysis of 171 functional studies reporting cingulate activation was performed. Seven different cognitive conditions were selected and peak activation coordinates were plotted to create maps of functional localization within the cingulate cortex. Regional functional specialization was found to be related to regional differences in probabilistic anatomical connectivity.

Antiaging Gene Klotho Regulates Adrenal CYP11B2 Expression and Aldosterone Synthesis.

PubMed

Zhou, Xiaoli; Chen, Kai; Wang, Yongjun; Schuman, Mariano; Lei, Han; Sun, Zhongjie

2016-06-01

Deficiency of the antiaging gene Klotho (KL) induces renal damage and hypertension through unknown mechanisms. In this study, we assessed whether KL regulates expression of CYP11B2, a key rate-limiting enzyme in aldosterone synthesis, in adrenal glands. We found that haplodeficiency of KL(+/-) in mice increased the plasma level of aldosterone by 16 weeks of age, which coincided with spontaneous and persistent elevation of BP. Blockade of aldosterone actions by eplerenone reversed KL deficiency-induced hypertension and attenuated the kidney damage. Protein expression of CYP11B2 was upregulated in adrenal cortex of KL(+/-) mice. KL and CYP11B2 proteins colocalized in adrenal zona glomerulosa cells. Silencing of KL upregulated and overexpression of KL downregulated CYP11B2 expression in human adrenocortical cells. Notably, silencing of KL decreased expression of SF-1, a negative transcription factor of CYP11B2, but increased phosphorylation of ATF2, a positive transcription factor of CYP11B2, which may contribute to upregulation of CYP11B2 expression. Therefore, these results show that KL regulates adrenal CYP11B2 expression. KL deficiency-induced spontaneous hypertension and kidney damage may be partially attributed to the upregulation of CYP11B2 expression and aldosterone synthesis. Copyright © 2016 by the American Society of Nephrology.

Spatial updating in human parietal cortex

NASA Technical Reports Server (NTRS)

Merriam, Elisha P.; Genovese, Christopher R.; Colby, Carol L.

2003-01-01

Single neurons in monkey parietal cortex update visual information in conjunction with eye movements. This remapping of stimulus representations is thought to contribute to spatial constancy. We hypothesized that a similar process occurs in human parietal cortex and that we could visualize it with functional MRI. We scanned subjects during a task that involved remapping of visual signals across hemifields. We observed an initial response in the hemisphere contralateral to the visual stimulus, followed by a remapped response in the hemisphere ipsilateral to the stimulus. We ruled out the possibility that this remapped response resulted from either eye movements or visual stimuli alone. Our results demonstrate that updating of visual information occurs in human parietal cortex.

Directional connectivity of resting state human fMRI data using cascaded ICA-PDC analysis.

PubMed

Silfverhuth, Minna J; Remes, Jukka; Starck, Tuomo; Nikkinen, Juha; Veijola, Juha; Tervonen, Osmo; Kiviniemi, Vesa

2011-11-01

Directional connectivity measures, such as partial directed coherence (PDC), give us means to explore effective connectivity in the human brain. By utilizing independent component analysis (ICA), the original data-set reduction was performed for further PDC analysis. To test this cascaded ICA-PDC approach in causality studies of human functional magnetic resonance imaging (fMRI) data. Resting state group data was imaged from 55 subjects using a 1.5 T scanner (TR 1800 ms, 250 volumes). Temporal concatenation group ICA in a probabilistic ICA and further repeatability runs (n = 200) were overtaken. The reduced data-set included the time series presentation of the following nine ICA components: secondary somatosensory cortex, inferior temporal gyrus, intracalcarine cortex, primary auditory cortex, amygdala, putamen and the frontal medial cortex, posterior cingulate cortex and precuneus, comprising the default mode network components. Re-normalized PDC (rPDC) values were computed to determine directional connectivity at the group level at each frequency. The integrative role was suggested for precuneus while the role of major divergence region may be proposed to primary auditory cortex and amygdala. This study demonstrates the potential of the cascaded ICA-PDC approach in directional connectivity studies of human fMRI.

Understanding Kidney Disease: Toward the Integration of Regulatory Networks Across Species

PubMed Central

Ju, Wenjun; Brosius, Frank C.

2010-01-01

Animal models have long been useful in investigating both normal and abnormal human physiology. Systems biology provides a relatively new set of approaches to identify similarities and differences between animal models and humans that may lead to a more comprehensive understanding of human kidney pathophysiology. In this review, we briefly describe how genome-wide analyses of mouse models have helped elucidate features of human kidney diseases, discuss strategies to achieve effective network integration, and summarize currently available web-based tools that may facilitate integration of data across species. The rapid progress in systems biology and orthology, as well as the advent of web-based tools to facilitate these processes, now make it possible to take advantage of knowledge from distant animal species in targeted identification of regulatory networks that may have clinical relevance for human kidney diseases. PMID:21044762

Renal subcapsular rim sign. Radionuclide pattern

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howman-Giles, R.; Gett, M.; Roy, P.

1986-04-01

The renal cortical rim sign is a radiological term describing the thin peripheral nephrogram of 2-4 mm thick which is from the peri-renal capsular collateral circulation in an otherwise nonfunctioning kidney. Radionuclides are used frequently in the estimation of renal function. A neonate with renal vein thrombosis demonstrated a rim sign on renal scan with Technetium DTPA. The rim sign on renal scan can be differentiated from severe hydronephrosis or multicystic kidney both of which may have a peripheral thin cortex which functions late on the renal scan. The rim sign in renal vein thrombosis was best visualized during themore » early blood pool phase when there was a considerable amount of radioactivity in the blood pool.« less

Kidney stone matrix proteins ameliorate calcium oxalate monohydrate induced apoptotic injury to renal epithelial cells.

PubMed

Narula, Shifa; Tandon, Simran; Singh, Shrawan Kumar; Tandon, Chanderdeep

2016-11-01

Kidney stone formation is a highly prevalent disease, affecting 8-10% of the human population worldwide. Proteins are the major constituents of human kidney stone's organic matrix and considered to play critical role in the pathogenesis of disease but their mechanism of modulation still needs to be explicated. Therefore, in this study we investigated the effect of human kidney stone matrix proteins on the calcium oxalate monohydrate (COM) mediated cellular injury. The renal epithelial cells (MDCK) were exposed to 200μg/ml COM crystals to induce injury. The effect of proteins isolated from human kidney stone was studied on COM injured cells. The alterations in cell-crystal interactions were examined by phase contrast, polarizing, fluorescence and scanning electron microscopy. Moreover, its effect on the extent of COM induced cell injury, was quantified by flow cytometric analysis. Our study indicated the antilithiatic potential of human kidney stone proteins on COM injured MDCK cells. Flow cytometric analysis and fluorescence imaging ascertained that matrix proteins decreased the extent of apoptotic injury caused by COM crystals on MDCK cells. Moreover, the electron microscopic studies of MDCK cells revealed that matrix proteins caused significant dissolution of COM crystals, indicating cytoprotection against the impact of calcium oxalate injury. The present study gives insights into the mechanism implied by urinary proteins to restrain the pathogenesis of kidney stone disease. This will provide a better understanding of the formation of kidney stones which can be useful for the proper management of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Behaviorally Relevant Abstract Object Identity Representation in the Human Parietal Cortex

PubMed Central

Jeong, Su Keun

2016-01-01

The representation of object identity is fundamental to human vision. Using fMRI and multivoxel pattern analysis, here we report the representation of highly abstract object identity information in human parietal cortex. Specifically, in superior intraparietal sulcus (IPS), a region previously shown to track visual short-term memory capacity, we found object identity representations for famous faces varying freely in viewpoint, hairstyle, facial expression, and age; and for well known cars embedded in different scenes, and shown from different viewpoints and sizes. Critically, these parietal identity representations were behaviorally relevant as they closely tracked the perceived face-identity similarity obtained in a behavioral task. Meanwhile, the task-activated regions in prefrontal and parietal cortices (excluding superior IPS) did not exhibit such abstract object identity representations. Unlike previous studies, we also failed to observe identity representations in posterior ventral and lateral visual object-processing regions, likely due to the greater amount of identity abstraction demanded by our stimulus manipulation here. Our MRI slice coverage precluded us from examining identity representation in anterior temporal lobe, a likely region for the computing of identity information in the ventral region. Overall, we show that human parietal cortex, part of the dorsal visual processing pathway, is capable of holding abstract and complex visual representations that are behaviorally relevant. These results argue against a “content-poor” view of the role of parietal cortex in attention. Instead, the human parietal cortex seems to be “content rich” and capable of directly participating in goal-driven visual information representation in the brain. SIGNIFICANCE STATEMENT The representation of object identity (including faces) is fundamental to human vision and shapes how we interact with the world. Although object representation has traditionally been associated with human occipital and temporal cortices, here we show, by measuring fMRI response patterns, that a region in the human parietal cortex can robustly represent task-relevant object identities. These representations are invariant to changes in a host of visual features, such as viewpoint, and reflect an abstract level of representation that has not previously been reported in the human parietal cortex. Critically, these neural representations are behaviorally relevant as they closely track the perceived object identities. Human parietal cortex thus participates in the moment-to-moment goal-directed visual information representation in the brain. PMID:26843642

Neural representations of faces and body parts in macaque and human cortex: a comparative FMRI study.

PubMed

Pinsk, Mark A; Arcaro, Michael; Weiner, Kevin S; Kalkus, Jan F; Inati, Souheil J; Gross, Charles G; Kastner, Sabine

2009-05-01

Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part-selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part-selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between the two species and provide an initial step toward establishing functionally homologous category-selective areas.

Neural Representations of Faces and Body Parts in Macaque and Human Cortex: A Comparative fMRI Study

PubMed Central

Pinsk, Mark A.; Arcaro, Michael; Weiner, Kevin S.; Kalkus, Jan F.; Inati, Souheil J.; Gross, Charles G.; Kastner, Sabine

2009-01-01

Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part–selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part–selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between the two species and provide an initial step toward establishing functionally homologous category-selective areas. PMID:19225169

Oxytocin- and arginine vasopressin-containing fibers in the cortex of humans, chimpanzees, and rhesus macaques.

PubMed

Rogers, Christina N; Ross, Amy P; Sahu, Shweta P; Siegel, Ethan R; Dooyema, Jeromy M; Cree, Mary Ann; Stopa, Edward G; Young, Larry J; Rilling, James K; Albers, H Elliott; Preuss, Todd M

2018-05-24

Oxytocin (OT) and arginine-vasopressin (AVP) are involved in the regulation of complex social behaviors across a wide range of taxa. Despite this, little is known about the neuroanatomy of the OT and AVP systems in most non-human primates, and less in humans. The effects of OT and AVP on social behavior, including aggression, mating, and parental behavior, may be mediated primarily by the extensive connections of OT- and AVP-producing neurons located in the hypothalamus with the basal forebrain and amygdala, as well as with the hypothalamus itself. However, OT and AVP also influence social cognition, including effects on social recognition, cooperation, communication, and in-group altruism, which suggests connectivity with cortical structures. While OT and AVP V1a receptors have been demonstrated in the cortex of rodents and primates, and intranasal administration of OT and AVP has been shown to modulate cortical activity, there is to date little evidence that OT-and AVP-containing neurons project into the cortex. Here, we demonstrate the existence of OT- and AVP-containing fibers in cortical regions relevant to social cognition using immunohistochemistry in humans, chimpanzees, and rhesus macaques. OT-immunoreactive fibers were found in the straight gyrus of the orbitofrontal cortex as well as the anterior cingulate gyrus in human and chimpanzee brains, while no OT-immunoreactive fibers were found in macaque cortex. AVP-immunoreactive fibers were observed in the anterior cingulate gyrus in all species, as well as in the insular cortex in humans, and in a more restricted distribution in chimpanzees. This is the first report of OT and AVP fibers in the cortex in human and non-human primates. Our findings provide a potential mechanism by which OT and AVP might exert effects on brain regions far from their production site in the hypothalamus, as well as potential species differences in the behavioral functions of these target regions. © 2018 Wiley Periodicals, Inc.

Using optical coherence tomography (OCT) to evaluate the status of human donor kidneys (Conference Presentation)

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Konkel, Brandon; Anderson, Erik; Stein, Matthew; Cooper, Matthew; Verbesey, Jennifer E.; Ghasemian, Seyed; Chen, Yu

2016-02-01

The main cause of delayed renal function following the transplant of donor kidneys is ischemic induced acute tubular necrosis (ATN). The ability to determine the degree of ATN suffered by donor kidneys prior to their transplant would enable transplant surgeons to use kidneys that might otherwise be discarded and better predict post-transplant renal function. Currently, there are no reliable tests to determine the extent of ATN of donor kidneys prior to their transplant. In ongoing clinical trials, we have been using optical coherence tomography (OCT) to non-invasively image the superficial proximal tubules of human donor kidneys prior to and following transplant, and correlate these observations with post-transplant renal function. Thus far we have studied over 40 living donor kidneys and 10 cadaver donor kidneys, and demonstrated that this imaging can be performed in a sterile and expeditious fashion in the operating room (OR). Because of many variables associated with a diverse population of donors/recipients and transplant operation parameters, more transplant data must be collected prior to drawing definite conclusions. Nevertheless, our observations have thus far mirrored our previously published laboratory results indicating that damage to the kidney proximal tubules as indicated by tubule swelling is a good measure of post-transplant ATN and delayed graft function. We conclude that OCT is a useful procedure for analyzing human donor kidneys.

Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure.

PubMed

Baba, Asuka; Tachi, Masahiro; Ejima, Yutaka; Endo, Yasuhiro; Toyama, Hiroaki; Saito, Kazutomo; Abe, Nozomu; Yamauchi, Masanori; Miura, Chieko; Kazama, Itsuro

2017-02-01

Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. © 2016 Asian Pacific Society of Nephrology.

The human cerebral cortex is neither one nor many: neuronal distribution reveals two quantitatively different zones in the gray matter, three in the white matter, and explains local variations in cortical folding

PubMed Central

Ribeiro, Pedro F. M.; Ventura-Antunes, Lissa; Gabi, Mariana; Mota, Bruno; Grinberg, Lea T.; Farfel, José M.; Ferretti-Rebustini, Renata E. L.; Leite, Renata E. P.; Filho, Wilson J.; Herculano-Houzel, Suzana

2013-01-01

The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex) the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital) that differ in how neurons are distributed across their gray matter volume and in three zones (prefrontal, occipital, and non-occipital) that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non-occipital areas. PMID:24032005

Exceptional Evolutionary Expansion of Prefrontal Cortex in Great Apes and Humans.

PubMed

Smaers, Jeroen B; Gómez-Robles, Aida; Parks, Ashley N; Sherwood, Chet C

2017-03-06

One of the enduring questions that has driven neuroscientific enquiry in the last century has been the nature of differences in the prefrontal cortex of humans versus other animals [1]. The prefrontal cortex has drawn particular interest due to its role in a range of evolutionarily specialized cognitive capacities such as language [2], imagination [3], and complex decision making [4]. Both cytoarchitectonic [5] and comparative neuroimaging [6] studies have converged on the conclusion that the proportion of prefrontal cortex in the human brain is greatly increased relative to that of other primates. However, considering the tremendous overall expansion of the neocortex in human evolution, it has proven difficult to ascertain whether this extent of prefrontal enlargement follows general allometric growth patterns, or whether it is exceptional [1]. Species' adherence to a common allometric relationship suggests conservation through phenotypic integration, while species' deviations point toward the occurrence of shifts in genetic and/or developmental mechanisms. Here we investigate prefrontal cortex scaling across anthropoid primates and find that great ape and human prefrontal cortex expansion are non-allometrically derived features of cortical organization. This result aligns with evidence for a developmental heterochronic shift in human prefrontal growth [7, 8], suggesting an association between neurodevelopmental changes and cortical organization on a macroevolutionary scale. The evolutionary origin of non-allometric prefrontal enlargement is estimated to lie at the root of great apes (∼19-15 mya), indicating that selection for changes in executive cognitive functions characterized both great ape and human cortical organization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Susceptibility of human liver cells to porcine endogenous retrovirus.

PubMed

Lin, Xinzi; Qi, Lin; Li, Zhiguo; Chi, Hao; Lin, Wanjun; Wang, Yan; Jiang, Zesheng; Pan, Mingxin; Gao, Yi

2013-12-01

The risk of porcine endogenous retrovirus infection is a major barrier for pig-to-human xenotransplant. Porcine endogenous retrovirus, present in porcine cells, can infect many human and nonhuman primate cells in vitro, but there is no evidence available about in vitro infection of human liver cells. We investigated the susceptibility of different human liver cells to porcine endogenous retrovirus. The supernatant from a porcine kidney cell line was added to human liver cells, including a normal hepatocyte cell line (HL-7702 cells), primary hepatocytes (Phh cells), and a liver stellate cell line (Lx-2 cells), and to human embryonic kidney cells as a reference control. Expression of the porcine endogenous retrovirus antigen p15E in the human cells was evaluated with polymerase chain reaction, reverse transcription-polymerase chain reaction, and Western blot. The porcine endogenous retrovirus antigen p15E was not expressed in any human liver cells (HL-7702, Phh, or Lx-2 cells) that had been exposed to supernatants from porcine kidney cell lines. Porcine endogenous retrovirus-specific fragments were amplified in human kidney cells. Human liver cells tested were not susceptible to infection by porcine endogenous retrovirus. Therefore, not all human cells are susceptible to porcine endogenous retrovirus.

High phosphorus diet-induced changes in NaPi-IIb phosphate transporter expression in the rat kidney: DNA microarray analysis.

PubMed

Suyama, Tatsuya; Okada, Shinji; Ishijima, Tomoko; Iida, Kota; Abe, Keiko; Nakai, Yuji

2012-01-01

The mechanism by which phosphorus levels are maintained in the body was investigated by analyzing changes in gene expression in the rat kidney following administration of a high phosphorus (HP) diet. Male Wistar rats were divided into two groups and fed a diet containing 0.3% (control) or 1.2% (HP) phosphorous for 24 days. Phosphorous retention was not significantly increased in HP rats, but fractional excretion of phosphorus was significantly increased in the HP group compared to controls, with an excessive amount of the ingested phosphorus being passed through the body. DNA microarray analysis of kidney tissue from both groups revealed changes in gene expression profile induced by a HP diet. Among the genes that were upregulated, Gene Ontology (GO) terms related to ossification, collagen fibril organization, and inflammation and immune response were significantly enriched. In particular, there was significant upregulation of type IIb sodium-dependent phosphate transporter (NaPi-IIb) in the HP rat kidney compared to control rats. This upregulation was confirmed by in situ hybridization. Distinct signals for NaPi-IIb in both the cortex and medulla of the kidney were apparent in the HP group, while the corresponding signals were much weaker in the control group. Immunohistochemical analysis showed that NaPi-IIb localized to the basolateral side of kidney epithelial cells surrounding the urinary duct in HP rats but not in control animals. These data suggest that NaPi-IIb is upregulated in the kidney in response to the active excretion of phosphate in HP diet-fed rats.

A highly resistant structure between cuticle and cortex of human hair.

PubMed

Takahashi, T; Yoshida, S

2017-06-01

To clarify the presence and properties of a unique structure which is located between the cuticle and cortex of human hair. Whole hair fibre and longitudinally split hair were used. Treated with a mixture of urea, reductant and alkaline, hair was split at the interface between cuticle and cortex. The residues in the solution were observed by microscope, and the distribution of lipids and protein was determined. From the treated longitudinally split hair, a membrane-like structure which was located at the interface between cuticle and cortex was obtained. This structure showed especially high resistance against chemical treatment and was thought to be the region into which the proximal roots of the cuticle cells are embedded. It was supposed that some steryl glucoside-like lipid, of which the presence in the cuticle and cortex interface was previously reported, is located in this structure. This study proposed the presence of a membrane-like structure, which is highly resistant against chemical treatment, at the region between cuticle and cortex of human hair. This may protect cortex from external stimuli more firmly than the surface part of cuticle. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex

PubMed Central

Pinto, Joshua G. A.; Jones, David G.; Williams, C. Kate; Murphy, Kathryn M.

2015-01-01

Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and about alignment of synaptic age between animals and humans, has limited translation of neuroplasticity therapies. In this study, we quantified expression of a set of highly conserved pre- and post-synaptic proteins (Synapsin, Synaptophysin, PSD-95, Gephyrin) and found that synaptic development in human primary visual cortex (V1) continues into late childhood. Indeed, this is many years longer than suggested by neuroanatomical studies and points to a prolonged sensitive period for plasticity in human sensory cortex. In addition, during childhood we found waves of inter-individual variability that are different for the four proteins and include a stage during early development (<1 year) when only Gephyrin has high inter-individual variability. We also found that pre- and post-synaptic protein balances develop quickly, suggesting that maturation of certain synaptic functions happens within the 1 year or 2 of life. A multidimensional analysis (principle component analysis) showed that most of the variance was captured by the sum of the four synaptic proteins. We used that sum to compare development of human and rat visual cortex and identified a simple linear equation that provides robust alignment of synaptic age between humans and rats. Alignment of synaptic ages is important for age-appropriate targeting and effective translation of neuroplasticity therapies from the lab to the clinic. PMID:25729353

Measurement of renal tissue oxygenation with blood oxygen level-dependent MRI and oxygen transit modeling

PubMed Central

Morrell, Glen; Rusinek, Henry; Warner, Lizette; Vivier, Pierre-Hugues; Cheung, Alfred K.; Lerman, Lilach O.; Lee, Vivian S.

2014-01-01

Blood oxygen level-dependent (BOLD) MRI data of kidney, while indicative of tissue oxygenation level (Po2), is in fact influenced by multiple confounding factors, such as R2, perfusion, oxygen permeability, and hematocrit. We aim to explore the feasibility of extracting tissue Po2 from renal BOLD data. A method of two steps was proposed: first, a Monte Carlo simulation to estimate blood oxygen saturation (SHb) from BOLD signals, and second, an oxygen transit model to convert SHb to tissue Po2. The proposed method was calibrated and validated with 20 pigs (12 before and after furosemide injection) in which BOLD-derived tissue Po2 was compared with microprobe-measured values. The method was then applied to nine healthy human subjects (age: 25.7 ± 3.0 yr) in whom BOLD was performed before and after furosemide. For the 12 pigs before furosemide injection, the proposed model estimated renal tissue Po2 with errors of 2.3 ± 5.2 mmHg (5.8 ± 13.4%) in cortex and −0.1 ± 4.5 mmHg (1.7 ± 18.1%) in medulla, compared with microprobe measurements. After injection of furosemide, the estimation errors were 6.9 ± 3.9 mmHg (14.2 ± 8.4%) for cortex and 2.6 ± 4.0 mmHg (7.7 ± 11.5%) for medulla. In the human subjects, BOLD-derived medullary Po2 increased from 16.0 ± 4.9 mmHg (SHb: 31 ± 11%) at baseline to 26.2 ± 3.1 mmHg (SHb: 53 ± 6%) at 5 min after furosemide injection, while cortical Po2 did not change significantly at ∼58 mmHg (SHb: 92 ± 1%). Our proposed method, validated with a porcine model, appears promising for estimating tissue Po2 from renal BOLD MRI data in human subjects. PMID:24452640

Laryngeal Motor Cortex and Control of Speech in Humans

PubMed Central

Simonyan, Kristina; Horwitz, Barry

2011-01-01

Speech production is one of the most complex and rapid motor behaviors and involves a precise coordination of over 100 laryngeal, orofacial and respiratory muscles. Yet, we lack a complete understanding of laryngeal motor cortical control during production of speech and other voluntary laryngeal behaviors. In recent years, a number of studies have confirmed the laryngeal motor cortical representation in humans and provided some information about its interactions with other cortical and subcortical regions that are principally involved in vocal motor control of speech production. In this review, we discuss the organization of the peripheral and central laryngeal control based on neuroimaging and electrical stimulation studies in humans and neuroanatomical tracing studies in non-human primates. We hypothesize that the location of the laryngeal motor cortex in the primary motor cortex and its direct connections with the brainstem laryngeal motoneurons in humans, as oppose to its location in the premotor cortex with only indirect connections to the laryngeal motoneurons in non-human primates, may represent one of the major evolutionary developments in humans towards the ability to speak and vocalize voluntarily. PMID:21362688

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beaumont, K.; Vaughn, D.A.; Fanestil, D.D.

Thiazides and related diuretics inhibit NaCl reabsorption in the distal tubule through an unknown mechanism. The authors report here that ({sup 3}H)metolazone, a diuretic with a thiazide-like mechanism of action, labels a site in rat kidney membranes that has characteristics of the thiazide-sensitive ion transporter. ({sup 3}H)Metolazone bound with high affinity to a site with a density of 0.717 pmol/mg of protein in kidney membranes. The binding site was localized to the renal cortex, with little or not binding in other kidney regions and 11 other tissues. The affinities of thiazide-type diuretics for this binding site were significantly correlated withmore » their clinical potency. Halide anions specifically inhibited high-affinity binding of ({sup 3}H)metolazone to this site. ({sup 3})Metolazone also bound with lower affinity to sites present in kidney as well as in liver, testis, lung, brain, heart, and other tissues. Calcium antagonists and certain smooth muscle relaxants had K{sub i} values of 0.6-10 {mu}M for these low-affinity sites, which were not inhibited by most of the thiazide diuretics tested. Properties of the high-affinity ({sup 3}H)metolazone binding site are consistent with its identity as the receptor for thiazide-type diuretics.« less

Renal dendritic cells sample blood-borne antigen and guide T-cell migration to the kidney by means of intravascular processes.

PubMed

Yatim, Karim M; Gosto, Minja; Humar, Rishab; Williams, Amanda L; Oberbarnscheidt, Martin H

2016-10-01

Bony fish are among the first vertebrates to possess an innate and adaptive immune system. In these species, the kidney has a dual function: filtering solutes similar to mammals and acting as a lymphoid organ responsible for hematopoiesis and antigen processing. Recent studies have shown that the mammalian kidney has an extensive network of mononuclear phagocytes, whose function is not fully understood. Here, we employed two-photon intravital microscopy of fluorescent reporter mice to demonstrate that renal dendritic cells encase the microvasculature in the cortex, extend dendrites into the peritubular capillaries, and sample the blood for antigen. We utilized a mouse model of systemic bacterial infection as well as immune complexes to demonstrate antigen uptake by renal dendritic cells. As a consequence, renal dendritic cells mediated T-cell migration into the kidney in an antigen-dependent manner in the setting of bacterial infection. Thus, renal dendritic cells may be uniquely positioned to play an important role not only in surveillance of systemic infection but also in local infection and autoimmunity. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Mass Spectrometry Imaging of Drug Related Crystal-Like Structures in Formalin-Fixed Frozen and Paraffin-Embedded Rabbit Kidney Tissue Sections

NASA Astrophysics Data System (ADS)

Bruinen, Anne L.; van Oevelen, Cateau; Eijkel, Gert B.; Van Heerden, Marjolein; Cuyckens, Filip; Heeren, Ron M. A.

2016-01-01

A multimodal mass spectrometry imaging (MSI) based approach was used to characterize the molecular content of crystal-like structures in a frozen and paraffin embedded piece of a formalin-fixed rabbit kidney. Matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) imaging and desorption electrospray ionization (DESI) mass spectrometry imaging were combined to analyze the frozen and paraffin embedded sample without further preparation steps to remove the paraffin. The investigated rabbit kidney was part of a study on a drug compound in development, in which severe renal toxicity was observed in dosed rabbits. Histological examination of the kidney showed tubular degeneration with precipitation of crystal-like structures in the cortex, which were assumed to cause the renal toxicity. The MS imaging approach was used to find out whether the crystal-like structures were composed of the drug compound, metabolites, or an endogenous compound as a reaction to the drug administration. The generated MALDI-MSI data were analyzed using principal component analysis. In combination with the MS/MS results, this way of data processing demonstrates that the crystal structures were mainly composed of metabolites and relatively little parent drug.

Urea and impairment of the Gut-Kidney axis in Chronic Kidney Disease.

PubMed

Di Iorio, Biagio Raffaele; Marzocco, Stefania; Nardone, Luca; Sirico, Marilisa; De Simone, Emanuele; Di Natale, Gabriella; Di Micco, Lucia

2017-12-05

Gut microbiota can be considered a real organ coordinating health and wellness of our body. It is made of more than 100 trillions of microorganisms, thus about 3 times higher than the number of human body cells and more than 150 times than human genes containing 1000 different microbe species. It has been described a symbiotic relationship between gut and kidney, confirmed by several observations. This is a bi-directional relation with a mutual influence, even when kidney disease occurs, and consequent alterations of intestinal microbiota and production of uremic toxins, that in turn worsens kidney disease and its progression. Our review analyzes the components of gut-kidney axis and relative clinical consequences. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Ultrastructural characterization of atrial natriuretic peptide receptors (ANP-R) mRNA expression in rat kidney cortex.

PubMed

Grandclément, B; Morel, G

1998-06-01

Atrial natriuretic peptide (ANP) and two complementary peptides named brain natriuretic peptide and C-type natriuretic peptide are involved in diuresis, natriuresis, hypotension and vasorelaxation. Their actions are mediated by highly selective and specific ANP receptors. Three subtypes have been characterized and cloned: ANP receptor A, -B and -C. In the present study, the mRNA for each subtype was detected by ultrastructural in situ hybridization on ultrathin sections of Lowicryl-embedded tissue and frozen tissue. The distribution of mRNA (visualized by gold particles) for each subtype was found to differ in different cells of the nephron. The three subtypes of this receptor family were expressed in all the parts of the nephron, but their expression levels were different. The ANPR-A mRNA was the most abundant in cells of glomerulus, proximal and distal tubules. The subtype C was the least expressed mRNA in glomerulus. In contrast, the subcellular localization of the three mRNAs was similar; they were found in the cytoplasmic matrix and the euchromatin of the nucleus. In conclusion, the differential expression of these mRNAs in kidney cortex indicates that these three peptides act directly in differing parts of nephron regions which are the glomerulus, the proximal and distal tubules.

The long-term label retaining population of the renal papilla arises through divergent regional growth of the kidney.

PubMed

Adams, Derek C; Oxburgh, Leif

2009-09-01

Long-term pulse chase experiments previously identified a sizable population of BrdU-retaining cells within the renal papilla. The origin of these cells has been unclear, and in this work we test the hypothesis that they become quiescent early during the course of kidney development and organ growth. Indeed, we find that BrdU-retaining cells of the papilla can be labeled only by pulsing with BrdU from embryonic (E) day 11.25 to postnatal (P) day 7, the approximate period of kidney development in the mouse. BrdU signal in the cortex and outer medulla is rapidly diluted by cellular proliferation during embryonic development and juvenile growth, whereas cells within the papilla differentiate and exit the cell cycle during organogenesis. Indeed, by E17.5, little or no active proliferation can be seen in the distal papilla, indicating maturation of this structure in a distal-to-proximal manner during organogenesis. We conclude that BrdU-retaining cells of the papilla represent a population of cells that quiesce during embryonic development and localize within a region of the kidney that matures early. We therefore propose that selective papillary retention of BrdU arises through a combination of regionalized slowing of, and exit from, the cell cycle within the papilla during the period of ongoing kidney development, and extensive proliferative growth of the juvenile kidney resulting in dilution of BrdU below the detection level in extra-papillary regions.

Density gradient electrophoresis of cultured human embryonic kidney cells

NASA Technical Reports Server (NTRS)

Plank, L. D.; Kunze, M. E.; Giranda, V.; Todd, P. W.

1985-01-01

Ground based confirmation of the electrophoretic heterogeneity of human embryonic kidney cell cultures, the general characterization of their electrophoretic migration, and observations on the general properties of cultures derived from electrophoretic subpopulations were studied. Cell migration in a density gradient electrophoresis column and cell electrophoretic mobility was determined. The mobility and heterogeneity of cultured human embryonic kidney cells with those of fixed rat erythrocytes as model test particle was compared. Electrophoretically separated cell subpopulations with respect to size, viability, and culture characteristics were examined.

How cortical neurons help us see: visual recognition in the human brain

PubMed Central

Blumberg, Julie; Kreiman, Gabriel

2010-01-01

Through a series of complex transformations, the pixel-like input to the retina is converted into rich visual perceptions that constitute an integral part of visual recognition. Multiple visual problems arise due to damage or developmental abnormalities in the cortex of the brain. Here, we provide an overview of how visual information is processed along the ventral visual cortex in the human brain. We discuss how neurophysiological recordings in macaque monkeys and in humans can help us understand the computations performed by visual cortex. PMID:20811161

Functional Topography of Human Auditory Cortex

PubMed Central

Rauschecker, Josef P.

2016-01-01

Functional and anatomical studies have clearly demonstrated that auditory cortex is populated by multiple subfields. However, functional characterization of those fields has been largely the domain of animal electrophysiology, limiting the extent to which human and animal research can inform each other. In this study, we used high-resolution functional magnetic resonance imaging to characterize human auditory cortical subfields using a variety of low-level acoustic features in the spectral and temporal domains. Specifically, we show that topographic gradients of frequency preference, or tonotopy, extend along two axes in human auditory cortex, thus reconciling historical accounts of a tonotopic axis oriented medial to lateral along Heschl's gyrus and more recent findings emphasizing tonotopic organization along the anterior–posterior axis. Contradictory findings regarding topographic organization according to temporal modulation rate in acoustic stimuli, or “periodotopy,” are also addressed. Although isolated subregions show a preference for high rates of amplitude-modulated white noise (AMWN) in our data, large-scale “periodotopic” organization was not found. Organization by AM rate was correlated with dominant pitch percepts in AMWN in many regions. In short, our data expose early auditory cortex chiefly as a frequency analyzer, and spectral frequency, as imposed by the sensory receptor surface in the cochlea, seems to be the dominant feature governing large-scale topographic organization across human auditory cortex. SIGNIFICANCE STATEMENT In this study, we examine the nature of topographic organization in human auditory cortex with fMRI. Topographic organization by spectral frequency (tonotopy) extended in two directions: medial to lateral, consistent with early neuroimaging studies, and anterior to posterior, consistent with more recent reports. Large-scale organization by rates of temporal modulation (periodotopy) was correlated with confounding spectral content of amplitude-modulated white-noise stimuli. Together, our results suggest that the organization of human auditory cortex is driven primarily by its response to spectral acoustic features, and large-scale periodotopy spanning across multiple regions is not supported. This fundamental information regarding the functional organization of early auditory cortex will inform our growing understanding of speech perception and the processing of other complex sounds. PMID:26818527

Epithelial chloride channel. Development of inhibitory ligands

PubMed Central

1987-01-01

Chloride channels are present in the majority of epithelial cells, where they mediate absorption or secretion of NaCl. Although the absorptive and secretory channels are well characterized in terms of their electrophysiological behavior, there is a lack of pharmacological ligands that can aid us in further functional and eventually molecular characterization. To obtain such ligands, we prepared membrane vesicles from bovine kidney cortex and apical membrane vesicles from trachea and found that they contain a chloride transport process that is electrically conductive. This conductance was reduced by preincubating the vesicles in media containing ATP or ATP-gamma-S, but not beta- methylene ATP, which suggests that the membranes contain a kinase that can close the channels. We then screened compounds derived from three classes: indanyloxyacetic acid (IAA), anthranilic acid (AA), and ethacrynic acid. We identified potent inhibitors from the IAA and the AA series. We tritiated IAA-94 and measured binding of this ligand to the kidney cortex membrane vesicles and found a high-affinity binding site whose dissociation constant (0.6 microM) was similar to the inhibition constant (1 microM). There was a good correlation between the inhibitory potency of several IAA derivatives and their efficacy in displacing [3H]IAA-94 from its binding site. Further, other chloride channel inhibitors, including AA derivatives, ethacrynic acid, bumetanide, and DIDS, also displaced the ligand from its binding site. A similar conductance was found in apical membrane vesicles from bovine trachea that was also inhibited by IAA-94 and AA-130B, but the inhibitory effects of these compounds were weaker than their effects on the renal cortex channel. The two drugs were also less potent in displacing [3H]IAA-94 from the tracheal binding site. PMID:2450168

Accounting for oxygen in the renal cortex: a computational study of factors that predispose the cortex to hypoxia.

PubMed

Lee, Chang-Joon; Gardiner, Bruce S; Ngo, Jennifer P; Kar, Saptarshi; Evans, Roger G; Smith, David W

2017-08-01

We develop a pseudo-three-dimensional model of oxygen transport for the renal cortex of the rat, incorporating both the axial and radial geometry of the preglomerular circulation and quantitative information regarding the surface areas and transport from the vasculature and renal corpuscles. The computational model was validated by simulating four sets of published experimental studies of renal oxygenation in rats. Under the control conditions, the predicted cortical tissue oxygen tension ([Formula: see text]) or microvascular oxygen tension (µPo 2 ) were within ±1 SE of the mean value observed experimentally. The predicted [Formula: see text] or µPo 2 in response to ischemia-reperfusion injury, acute hemodilution, blockade of nitric oxide synthase, or uncoupling mitochondrial respiration, were within ±2 SE observed experimentally. We performed a sensitivity analysis of the key model parameters to assess their individual or combined impact on the predicted [Formula: see text] and µPo 2 The model parameters analyzed were as follows: 1 ) the major determinants of renal oxygen delivery ([Formula: see text]) (arterial blood Po 2 , hemoglobin concentration, and renal blood flow); 2 ) the major determinants of renal oxygen consumption (V̇o 2 ) [glomerular filtration rate (GFR) and the efficiency of oxygen utilization for sodium reabsorption (β)]; and 3) peritubular capillary surface area (PCSA). Reductions in PCSA by 50% were found to profoundly increase the sensitivity of [Formula: see text] and µPo 2 to the major the determinants of [Formula: see text] and V̇o 2 The increasing likelihood of hypoxia with decreasing PCSA provides a potential explanation for the increased risk of acute kidney injury in some experimental animals and for patients with chronic kidney disease. Copyright © 2017 the American Physiological Society.

Kidney of giraffes.

PubMed

Maluf, Noble Suydam Rustem

2002-06-01

This study focuses on certain aspects of the renal structure of the giraffe, with some implications as to its function. About 4,000 collecting ducts open at the truncated end of a curved crest that juts into the renal pelvis as the inner medulla (IM). Extensions of the pelvis pass between the medullary (MP) and vascular (VP) processes almost to the corticomedullary border. The MPs contain an IM and an outer medulla (OM) containing clusters of capillaries (vascular bundles). The VPs contain the interlobar arteries and veins. All of the IM and almost all of the OM, with its vascular bundles, are bathed with pelvic urine. The cortex comprises 63% of the parenchyma. The OM has nine times the mass of the IM. The IM comprises 4% of the parenchyma. The ratio of mass of the adult cortex to the medulla is 1.7:1.0, and the number of glomeruli per kidney is 6.6 x 10(6). Glomerular mass is 6.2-6.7% of renal mass in the adult and 5.2% in the 6-month-old calf. The dimensions of the glomerular capsules are the same across the thickness of the cortex. Every terminal collecting duct drains an estimated 1,650 nephrons. In the adult giraffe the ratio of thickness of the muscularis of the main renal artery (RA) to its diameter is 0.117 (right RA) and 0.132 (left RA). These ratios are close to those in rhinoceros and ox but greater than in man. The visceral arteries (celiac, anterior mesenteric, and renal) have about the same muscularis : diameter ratio. Giraffes have arterial hypertension, but atherosclerosis is apparently absent and serum lipid fractions are low. Copyright 2002 Wiley-Liss, Inc.

Body Topography Parcellates Human Sensory and Motor Cortex.

PubMed

Kuehn, Esther; Dinse, Juliane; Jakobsen, Estrid; Long, Xiangyu; Schäfer, Andreas; Bazin, Pierre-Louis; Villringer, Arno; Sereno, Martin I; Margulies, Daniel S

2017-07-01

The cytoarchitectonic map as proposed by Brodmann currently dominates models of human sensorimotor cortical structure, function, and plasticity. According to this model, primary motor cortex, area 4, and primary somatosensory cortex, area 3b, are homogenous areas, with the major division lying between the two. Accumulating empirical and theoretical evidence, however, has begun to question the validity of the Brodmann map for various cortical areas. Here, we combined in vivo cortical myelin mapping with functional connectivity analyses and topographic mapping techniques to reassess the validity of the Brodmann map in human primary sensorimotor cortex. We provide empirical evidence that area 4 and area 3b are not homogenous, but are subdivided into distinct cortical fields, each representing a major body part (the hand and the face). Myelin reductions at the hand-face borders are cortical layer-specific, and coincide with intrinsic functional connectivity borders as defined using large-scale resting state analyses. Our data extend the Brodmann model in human sensorimotor cortex and suggest that body parts are an important organizing principle, similar to the distinction between sensory and motor processing. © The Author 2017. Published by Oxford University Press.

A Review of the Diagnosis and Treatment of Ochratoxin A Inhalational Exposure Associated with Human Illness and Kidney Disease including Focal Segmental Glomerulosclerosis

PubMed Central

Hope, Janette H.; Hope, Bradley E.

2012-01-01

Ochratoxin A (OTA) exposure via ingestion and inhalation has been described in the literature to cause kidney disease in both animals and humans. This paper reviews Ochratoxin A and its relationship to human health and kidney disease with a focus on a possible association with focal segmental glomerulosclerosis (FSGS) in humans. Prevention and treatment strategies for OTA-induced illness are also discussed, including cholestyramine, a bile-acid-binding resin used as a sequestrant to reduce the enterohepatic recirculation of OTA. PMID:22253638

Reproducibility of MRI renal artery blood flow and BOLD measurements in patients with chronic kidney disease and healthy controls.

PubMed

Khatir, Dinah S; Pedersen, Michael; Jespersen, Bente; Buus, Niels H

2014-11-01

Determine the reproducibility of renal artery blood flow (RABF) and blood-oxygenation level dependent (R2 *) in patients with chronic kidney disease (CKD) and healthy controls. RABF and R2 * were measured in 11 CKD patients and 9 controls twice with 1- to 2-week interval. R2 * in the cortex and medulla were determined after breathing atmospheric air and 100% oxygen. Reproducibility was evaluated by coefficients of variation (CV), limits of agreements and intra-class coefficient calculated by variance components by maximum likelihood modeling. Single-kidney RABF (mL/min) for patients was: 170 ± 130 and 186 ± 137, and for controls: 365 ± 119 and 361 ± 107 (P < 0.05 versus patients), for first and second scans, respectively. RABF measurements were reproducible with a CV of 12.9% and 8.3% for patients and controls, respectively. Renal cortical R2 * was: 13.6 ± 0.9 and 13.5 ± 1.2 in patients (CV = 8.0%), and 13.8 ± 1.6 and 14.0 ± 1.5 in controls (CV = 5.6%), while medullary R2 *(s(-1) ) was: 26.9 ± 2.0 and 27.0 ± 4.0 (CV = 8.0%) in patients, and 26.0 ± 2.4 and 26.1 ± 2.1 (CV = 3.6%) in controls, for first and second scans, respectively. In both groups R2 * in medulla decreased after breathing 100% oxygen. The reproducibility was high for both RABF and R2 * in patients and controls, particularly in the cortex. Inhalation of 100% oxygen reduced medullary R2 *. © 2013 Wiley Periodicals, Inc.

Gonadectomy prevents the increase in blood pressure and glomerular injury in angiotensin-converting enzyme 2 knockout diabetic male mice. Effects on renin-angiotensin system.

PubMed

Clotet, Sergi; Soler, María José; Rebull, Marta; Gimeno, Javier; Gurley, Susan B; Pascual, Julio; Riera, Marta

2016-09-01

Angiotensin-converting enzyme 2 (ACE2) deletion worsens kidney injury, and its amplification ameliorates diabetic nephropathy. Male sex increases the incidence, prevalence, and progression of chronic kidney disease in our environment. Here, we studied the effect of ACE2 deficiency and gonadectomy (GDX) on diabetic nephropathy and its relationship with fibrosis, protein kinase B (Akt) activation, and the expression of several components of the renin-angiotensin system (RAS).Mice were injected with streptozotocin to induce diabetes and followed for 19 weeks. Physiological and renal parameters were studied in wild-type and ACE2 knockout (ACE2KO) male mice with and without GDX. Diabetic ACE2KO showed increased blood pressure (BP), glomerular injury, and renal fibrosis compared with diabetic wild-type. Gonadectomized diabetic ACE2KO presented a decrease in BP. In the absence of ACE2, GDX attenuated albuminuria and renal lesions, such as mesangial matrix expansion and podocyte loss. Both, α-smooth muscle actin accumulation and collagen deposition were significantly decreased in renal cortex of gonadectomized diabetic ACE2KO but not diabetic wild-type mice. GDX also reduced circulating ACE activity in ACE2KO mice. Loss of ACE2 modified the effect of GDX on cortical gene expression of RAS in diabetic mice. Akt phosphorylation in renal cortex was increased by diabetes and loss of ACE2 and decreased by GDX in control and diabetic ACE2KO but not in wild-type mice. Our results suggest that GDX may exert a protective effect within the kidney under pathological conditions of diabetes and ACE2 deficiency. This renoprotection may be ascribed to different mechanisms such as decrease in BP, modulation of RAS, and downregulation of Akt-related pathways.

Analyzing pitch chroma and pitch height in the human brain.

PubMed

Warren, Jason D; Uppenkamp, Stefan; Patterson, Roy D; Griffiths, Timothy D

2003-11-01

The perceptual pitch dimensions of chroma and height have distinct representations in the human brain: chroma is represented in cortical areas anterior to primary auditory cortex, whereas height is represented posterior to primary auditory cortex.

Spatial transcriptomic survey of human embryonic cerebral cortex by single-cell RNA-seq analysis.

PubMed

Fan, Xiaoying; Dong, Ji; Zhong, Suijuan; Wei, Yuan; Wu, Qian; Yan, Liying; Yong, Jun; Sun, Le; Wang, Xiaoye; Zhao, Yangyu; Wang, Wei; Yan, Jie; Wang, Xiaoqun; Qiao, Jie; Tang, Fuchou

2018-06-04

The cellular complexity of human brain development has been intensively investigated, although a regional characterization of the entire human cerebral cortex based on single-cell transcriptome analysis has not been reported. Here, we performed RNA-seq on over 4,000 individual cells from 22 brain regions of human mid-gestation embryos. We identified 29 cell sub-clusters, which showed different proportions in each region and the pons showed especially high percentage of astrocytes. Embryonic neurons were not as diverse as adult neurons, although they possessed important features of their destinies in adults. Neuron development was unsynchronized in the cerebral cortex, as dorsal regions appeared to be more mature than ventral regions at this stage. Region-specific genes were comprehensively identified in each neuronal sub-cluster, and a large proportion of these genes were neural disease related. Our results present a systematic landscape of the regionalized gene expression and neuron maturation of the human cerebral cortex.

The elephant brain in numbers

PubMed Central

Herculano-Houzel, Suzana; Avelino-de-Souza, Kamilla; Neves, Kleber; Porfírio, Jairo; Messeder, Débora; Mattos Feijó, Larissa; Maldonado, José; Manger, Paul R.

2014-01-01

What explains the superior cognitive abilities of the human brain compared to other, larger brains? Here we investigate the possibility that the human brain has a larger number of neurons than even larger brains by determining the cellular composition of the brain of the African elephant. We find that the African elephant brain, which is about three times larger than the human brain, contains 257 billion (109) neurons, three times more than the average human brain; however, 97.5% of the neurons in the elephant brain (251 billion) are found in the cerebellum. This makes the elephant an outlier in regard to the number of cerebellar neurons compared to other mammals, which might be related to sensorimotor specializations. In contrast, the elephant cerebral cortex, which has twice the mass of the human cerebral cortex, holds only 5.6 billion neurons, about one third of the number of neurons found in the human cerebral cortex. This finding supports the hypothesis that the larger absolute number of neurons in the human cerebral cortex (but not in the whole brain) is correlated with the superior cognitive abilities of humans compared to elephants and other large-brained mammals. PMID:24971054

78 FR 43218 - Notice of Kidney Interagency Coordinating Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Notice of Kidney Interagency Coordinating Committee Meeting SUMMARY: The Kidney Interagency Coordinating Committee (KICC) will hold a meeting on September 27, 2013, about interagency collaboration to improve outcomes in Chronic Kidney...

Effects of a restricted fetal growth environment on human kidney morphology, cell apoptosis and gene expression.

PubMed

Wang, Yan-Ping; Chen, Xu; Zhang, Zhi-Kun; Cui, Hong-Yan; Wang, Peng; Wang, Yue

2015-12-01

Kidney development is key to the onset of hypertension and cardiovascular diseases in adults, and in the fetal stage will be impaired by a lack of nutrients in utero in animal models. However, few human studies have been performed. Kidney samples from fetuses in a fetal growth restriction (FGR) environment were collected and the morphological characteristics were observed. Potentially molecular mechanisms were explored by analyzing apoptosis and kidney-development related gene expression. The results indicated that no malformations were observed in the kidney samples of the FGR group, but the mean kidney weight and volume were significantly decreased. Moreover, the ratio of apoptotic cells and Bax-positive cells was increased and the ratio of Bcl-2-positive cells was decreased in the FGR group, indicating potential apoptosis induction under an in utero FGR environment. Finally, aberrant expression of renin and angiotensinogen indicated potential kidney functional abnormalities in the FGR group. Our study suggested increased apoptosis and decreased renin and angiotensinogen expression during human kidney development in an FGR environment. The current results will be helpful to further explore the molecular mechanism of FGR and facilitate future studies of hypertension and cardiovascular diseases and the establishment of preventive methods. © The Author(s) 2014.

Beta Peak Frequencies at Rest Correlate with Endogenous GABA+/Cr Concentrations in Sensorimotor Cortex Areas

PubMed Central

Baumgarten, Thomas J.; Oeltzschner, Georg; Hoogenboom, Nienke; Wittsack, Hans-Jörg; Schnitzler, Alfons; Lange, Joachim

2016-01-01

Neuronal oscillatory activity in the beta band (15–30 Hz) is a prominent signal within the human sensorimotor cortex. Computational modeling and pharmacological modulation studies suggest an influence of GABAergic interneurons on the generation of beta band oscillations. Accordingly, studies in humans have demonstrated a correlation between GABA concentrations and power of beta band oscillations. It remains unclear, however, if GABA concentrations also influence beta peak frequencies and whether this influence is present in the sensorimotor cortex at rest and without pharmacological modulation. In the present study, we investigated the relation between endogenous GABA concentration (measured by magnetic resonance spectroscopy) and beta oscillations (measured by magnetoencephalography) at rest in humans. GABA concentrations and beta band oscillations were measured for left and right sensorimotor and occipital cortex areas. A significant positive linear correlation between GABA concentration and beta peak frequency was found for the left sensorimotor cortex, whereas no significant correlations were found for the right sensorimotor and the occipital cortex. The results show a novel connection between endogenous GABA concentration and beta peak frequency at rest. This finding supports previous results that demonstrated a connection between oscillatory beta activity and pharmacologically modulated GABA concentration in the sensorimotor cortex. Furthermore, the results demonstrate that for a predominantly right-handed sample, the correlation between beta band oscillations and endogenous GABA concentrations is evident only in the left sensorimotor cortex. PMID:27258089

Agmatine, a bioactive metabolite of arginine. Production, degradation, and functional effects in the kidney of the rat.

PubMed Central

Lortie, M J; Novotny, W F; Peterson, O W; Vallon, V; Malvey, K; Mendonca, M; Satriano, J; Insel, P; Thomson, S C; Blantz, R C

1996-01-01

Until recently, conversion of arginine to agmatine by arginine decarboxylase (ADC) was considered important only in plants and bacteria. In the following, we demonstrate ADC activity in the membrane-enriched fraction of brain, liver, and kidney cortex and medulla by radiochemical assay. Diamine oxidase, an enzyme shown here to metabolize agmatine, was localized by immunohistochemistry in kidney glomeruli and other nonrenal cells. Production of labeled agmatine, citrulline, and ornithine from [3H]arginine was demonstrated and endogenous agmatine levels (10(-6)M) in plasma ultrafiltrate and kidney were measured by HPLC. Microperfusion of agmatine into renal interstitium and into the urinary space of surface glomeruli of Wistar-Frömter rats produced reversible increases in nephron filtration rate (SNGFR) and absolute proximal reabsorption (APR). Renal denervation did not alter SNGFR effects but prevented APR changes. Yohimbine (an alpha 2 antagonist) microperfusion into the urinary space produced opposite effects to that of agmatine. Microperfusion of urinary space with BU-224 (microM), a synthetic imidazoline2 (I2) agonist, duplicated agmatine effects on SNGFR but not APR whereas an I1 agonist had no effect. Agmatine effects on SNGFR and APR are not only dissociable but appear to be mediated by different mechanisms. The production and degradation of this biologically active substance derived from arginine constitutes a novel endogenous regulatory system in the kidney. PMID:8567962

Estimates of segregation and overlap of functional connectivity networks in the human cerebral cortex.

PubMed

Yeo, B T Thomas; Krienen, Fenna M; Chee, Michael W L; Buckner, Randy L

2014-03-01

The organization of the human cerebral cortex has recently been explored using techniques for parcellating the cortex into distinct functionally coupled networks. The divergent and convergent nature of cortico-cortical anatomic connections suggests the need to consider the possibility of regions belonging to multiple networks and hierarchies among networks. Here we applied the Latent Dirichlet Allocation (LDA) model and spatial independent component analysis (ICA) to solve for functionally coupled cerebral networks without assuming that cortical regions belong to a single network. Data analyzed included 1000 subjects from the Brain Genomics Superstruct Project (GSP) and 12 high quality individual subjects from the Human Connectome Project (HCP). The organization of the cerebral cortex was similar regardless of whether a winner-take-all approach or the more relaxed constraints of LDA (or ICA) were imposed. This suggests that large-scale networks may function as partially isolated modules. Several notable interactions among networks were uncovered by the LDA analysis. Many association regions belong to at least two networks, while somatomotor and early visual cortices are especially isolated. As examples of interaction, the precuneus, lateral temporal cortex, medial prefrontal cortex and posterior parietal cortex participate in multiple paralimbic networks that together comprise subsystems of the default network. In addition, regions at or near the frontal eye field and human lateral intraparietal area homologue participate in multiple hierarchically organized networks. These observations were replicated in both datasets and could be detected (and replicated) in individual subjects from the HCP. © 2013.

Estimates of Segregation and Overlap of Functional Connectivity Networks in the Human Cerebral Cortex

PubMed Central

Yeo, BT Thomas; Krienen, Fenna M; Chee, Michael WL; Buckner, Randy L

2014-01-01

The organization of the human cerebral cortex has recently been explored using techniques for parcellating the cortex into distinct functionally coupled networks. The divergent and convergent nature of cortico-cortical anatomic connections suggests the need to consider the possibility of regions belonging to multiple networks and hierarchies among networks. Here we applied the Latent Dirichlet Allocation (LDA) model and spatial independent component analysis (ICA) to solve for functionally coupled cerebral networks without assuming that cortical regions belong to a single network. Data analyzed included 1,000 subjects from the Brain Genomics Superstruct Project (GSP) and 12 high quality individual subjects from the Human Connectome Project (HCP). The organization of the cerebral cortex was similar regardless of whether a winner-take-all approach or the more relaxed constraints of LDA (or ICA) were imposed. This suggests that large-scale networks may function as partially isolated modules. Several notable interactions among networks were uncovered by the LDA analysis. Many association regions belong to at least two networks, while somatomotor and early visual cortices are especially isolated. As examples of interaction, the precuneus, lateral temporal cortex, medial prefrontal cortex and posterior parietal cortex participate in multiple paralimbic networks that together comprise subsystems of the default network. In addition, regions at or near the frontal eye field and human lateral intraparietal area homologue participate in multiple hierarchically organized networks. These observations were replicated in both datasets and could be detected (and replicated) in individual subjects from the HCP. PMID:24185018

Purification of Recombinant Ebola Virus Glycoprotein and VP40 from a Human Cell Line

DTIC Science & Technology

2017-01-01

from a human cell line. Plasmids coding for the expression of these proteins were transiently transfected into human embryonic kidney cells 293 and...protein expression. Expi293F cells were derived from the line of human embryonic kidney cells 293 (i.e., HEK293 cells), and they were grown in a

Establishment of Donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion

DTIC Science & Technology

2016-09-01

specific immunosuppression. Induction of tolerance to the CTA is the ideal solution. Combined mixed allogeneic chimerism induction and kidney ...transplantation has been shown to induce robust tolerance to the kidney allograft despite transient mixed chimerism in non-human primates and humans...solution. Mixed chimerism induction via hematopoietic cell transplantation (HCT) has been shown to facilitate tolerance induction to kidney allografts

Angiogenin Mediates Cell-Autonomous Translational Control under Endoplasmic Reticulum Stress and Attenuates Kidney Injury

PubMed Central

Mami, Iadh; Bouvier, Nicolas; El Karoui, Khalil; Gallazzini, Morgan; Rabant, Marion; Laurent-Puig, Pierre; Li, Shuping; Tharaux, Pierre-Louis; Beaune, Philippe; Thervet, Eric; Chevet, Eric; Hu, Guo-Fu

2016-01-01

Endoplasmic reticulum (ER) stress is involved in the pathophysiology of kidney disease and aging, but the molecular bases underlying the biologic outcomes on the evolution of renal disease remain mostly unknown. Angiogenin (ANG) is a ribonuclease that promotes cellular adaptation under stress but its contribution to ER stress signaling remains elusive. In this study, we investigated the ANG-mediated contribution to the signaling and biologic outcomes of ER stress in kidney injury. ANG expression was significantly higher in samples from injured human kidneys than in samples from normal human kidneys, and in mouse and rat kidneys, ANG expression was specifically induced under ER stress. In human renal epithelial cells, ER stress induced ANG expression in a manner dependent on the activity of transcription factor XBP1, and ANG promoted cellular adaptation to ER stress through induction of stress granules and inhibition of translation. Moreover, the severity of renal lesions induced by ER stress was dramatically greater in ANG knockout mice (Ang−/−) mice than in wild-type mice. These results indicate that ANG is a critical mediator of tissue adaptation to kidney injury and reveal a physiologically relevant ER stress-mediated adaptive translational control mechanism. PMID:26195817

Neurochemical Characterization of PSA-NCAM+ Cells in the Human Brain and Phenotypic Quantification in Alzheimer's Disease Entorhinal Cortex.

PubMed

Murray, Helen C; Swanson, Molly E V; Dieriks, B Victor; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

2018-02-21

Polysialylated neural cell adhesion molecule (PSA-NCAM) is widely expressed in the adult human brain and facilitates structural remodeling of cells through steric inhibition of intercellular NCAM adhesion. We previously showed that PSA-NCAM immunoreactivity is decreased in the entorhinal cortex in Alzheimer's disease (AD). Based on available evidence, we hypothesized that a loss of PSA-NCAM + interneurons may underlie this reduction. PSA-NCAM expression by interneurons has previously been described in the human medial prefrontal cortex. Here we used postmortem human brain tissue to provide further evidence of PSA-NCAM + interneurons throughout the human hippocampal formation and additional cortical regions. Furthermore, PSA-NCAM + cell populations were assessed in the entorhinal cortex of normal and AD cases using fluorescent double labeling and manual cell counting. We found a significant decrease in the number of PSA-NCAM + cells per mm 2 in layer II and V of the entorhinal cortex, supporting our previous description of reduced PSA-NCAM immunoreactivity. Additionally, we found a significant decrease in the proportion of PSA-NCAM + cells that co-labeled with NeuN and parvalbumin, but no change in the proportion that co-labeled with calbindin or calretinin. These results demonstrate that PSA-NCAM is expressed by a variety of interneuron populations throughout the brain. Furthermore, that loss of PSA-NCAM expression by NeuN + cells predominantly contributes to the reduced PSA-NCAM immunoreactivity in the AD entorhinal cortex. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Bone pulsating metastasis due to renal cell carcinoma.

PubMed

Cınar, Murat; Derincek, Alihan; Karan, Belgin; Akpınar, Sercan; Tuncay, Cengiz

2010-11-01

Pulsation on the bone cortex surface is a rare condition. Pulsative palpation of the superficial-located bone tumors can be misperceived as an aneurysm. Fifty-eight-year-old man is presented with pulsating bone mass in his proximal tibia. During angiographic examination, hypervascular masses were diagnosed both at right kidney and at right proximal tibia. Renal cell carcinoma was diagnosed after abdominal CT scan. Proximal tibia biopsy was complicated with projectile bleeding.

Auditory connections and functions of prefrontal cortex

PubMed Central

Plakke, Bethany; Romanski, Lizabeth M.

2014-01-01

The functional auditory system extends from the ears to the frontal lobes with successively more complex functions occurring as one ascends the hierarchy of the nervous system. Several areas of the frontal lobe receive afferents from both early and late auditory processing regions within the temporal lobe. Afferents from the early part of the cortical auditory system, the auditory belt cortex, which are presumed to carry information regarding auditory features of sounds, project to only a few prefrontal regions and are most dense in the ventrolateral prefrontal cortex (VLPFC). In contrast, projections from the parabelt and the rostral superior temporal gyrus (STG) most likely convey more complex information and target a larger, widespread region of the prefrontal cortex. Neuronal responses reflect these anatomical projections as some prefrontal neurons exhibit responses to features in acoustic stimuli, while other neurons display task-related responses. For example, recording studies in non-human primates indicate that VLPFC is responsive to complex sounds including vocalizations and that VLPFC neurons in area 12/47 respond to sounds with similar acoustic morphology. In contrast, neuronal responses during auditory working memory involve a wider region of the prefrontal cortex. In humans, the frontal lobe is involved in auditory detection, discrimination, and working memory. Past research suggests that dorsal and ventral subregions of the prefrontal cortex process different types of information with dorsal cortex processing spatial/visual information and ventral cortex processing non-spatial/auditory information. While this is apparent in the non-human primate and in some neuroimaging studies, most research in humans indicates that specific task conditions, stimuli or previous experience may bias the recruitment of specific prefrontal regions, suggesting a more flexible role for the frontal lobe during auditory cognition. PMID:25100931

The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex.

PubMed

Self, Matthew W; Peters, Judith C; Possel, Jessy K; Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C; Roelfsema, Pieter R

2016-03-01

Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons' receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex.

The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex

PubMed Central

Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C.; Roelfsema, Pieter R.

2016-01-01

Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons’ receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex. PMID:27015604

Dissociation and Convergence of the Dorsal and Ventral Visual Streams in the Human Prefrontal Cortex

PubMed Central

Takahashi, Emi; Ohki, Kenichi; Kim, Dae-Shik

2012-01-01

Visual information is largely processed through two pathways in the primate brain: an object pathway from the primary visual cortex to the temporal cortex (ventral stream) and a spatial pathway to the parietal cortex (dorsal stream). Whether and to what extent dissociation exists in the human prefrontal cortex (PFC) has long been debated. We examined anatomical connections from functionally defined areas in the temporal and parietal cortices to the PFC, using noninvasive functional and diffusion-weighted magnetic resonance imaging. The right inferior frontal gyrus (IFG) received converging input from both streams, while the right superior frontal gyrus received input only from the dorsal stream. Interstream functional connectivity to the IFG was dynamically recruited only when both object and spatial information were processed. These results suggest that the human PFC receives dissociated and converging visual pathways, and that the right IFG region serves as an integrator of the two types of information. PMID:23063444

DHEA-induced modulation of renal gluconeogenesis, insulin sensitivity and plasma lipid profile in the control- and dexamethasone-treated rabbits. Metabolic studies.

PubMed

Kiersztan, Anna; Nagalski, Andrzej; Nalepa, Paweł; Tempes, Aleksandra; Trojan, Nina; Usarek, Michał; Jagielski, Adam K

2016-02-01

In view of antidiabetic and antiglucocorticoid effects of dehydroepiandrosterone (DHEA) both in vitro and in vivo studies were undertaken: (i) to elucidate the mechanism of action of both dexamethasone phosphate (dexP) and DHEA on glucose synthesis in primary cultured rabbit kidney-cortex tubules and (ii) to investigate the influence of DHEA on glucose synthesis, insulin sensitivity and plasma lipid profile in the control- and dexP-treated rabbits. Data show, that in cultured kidney-cortex tubules dexP significantly stimulated gluconeogenesis by increasing flux through fructose-1,6-bisphosphatase (FBPase). DexP-induced effects were dependent only upon glucocorticoid receptor. DHEA decreased glucose synthesis via inhibition of glucose-6-phosphatase (G6Pase) and suppressed the dexP-induced stimulation of renal gluconeogenesis. Studies with the use of inhibitors of DHEA metabolism in cultured renal tubules showed for the first time that DHEA directly affects renal gluconeogenesis. However, in view of analysis of glucocorticoids and DHEA metabolites levels in urine, it seems likely, that testosterone may also contribute to DHEA-evoked effects. In dexP-treated rabbits, plasma glucose level was not altered despite increased renal and hepatic FBPase and G6Pase activities, while a significant elevation of both plasma insulin and HOMA-IR was accompanied by a decline of ISI index. It thus appears that increased insulin levels were required to maintain normoglycaemia and to compensate the insulin resistance. DHEA alone affected neither plasma glucose nor lipid levels, while it increased insulin sensitivity and diminished both renal and hepatic G6Pase activities. Surprisingly, DHEA co-administrated with dexP did not alter insulin sensitivity, while it partially suppressed the dexP-induced elevation of renal G6Pase activity and plasma cholesterol and triglyceride contents. As (i) gluconeogenic pathway in rabbit is similar to that in human, and (ii) DHEA counteracts several dexP-evoked effects, it seems likely, that its supplementation might be beneficial to patients treated with glucocorticoids. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

The harmonic organization of auditory cortex.

PubMed

Wang, Xiaoqin

2013-12-17

A fundamental structure of sounds encountered in the natural environment is the harmonicity. Harmonicity is an essential component of music found in all cultures. It is also a unique feature of vocal communication sounds such as human speech and animal vocalizations. Harmonics in sounds are produced by a variety of acoustic generators and reflectors in the natural environment, including vocal apparatuses of humans and animal species as well as music instruments of many types. We live in an acoustic world full of harmonicity. Given the widespread existence of the harmonicity in many aspects of the hearing environment, it is natural to expect that it be reflected in the evolution and development of the auditory systems of both humans and animals, in particular the auditory cortex. Recent neuroimaging and neurophysiology experiments have identified regions of non-primary auditory cortex in humans and non-human primates that have selective responses to harmonic pitches. Accumulating evidence has also shown that neurons in many regions of the auditory cortex exhibit characteristic responses to harmonically related frequencies beyond the range of pitch. Together, these findings suggest that a fundamental organizational principle of auditory cortex is based on the harmonicity. Such an organization likely plays an important role in music processing by the brain. It may also form the basis of the preference for particular classes of music and voice sounds.

Fructose downregulates miR-330 to induce renal inflammatory response and insulin signaling impairment: Attenuation by morin.

PubMed

Gu, Ting-Ting; Song, Lin; Chen, Tian-Yu; Wang, Xing; Zhao, Xiao-Juan; Ding, Xiao-Qin; Yang, Yan-Zi; Pan, Ying; Zhang, Dong-Mei; Kong, Ling-Dong

2017-08-01

Fructose induces insulin resistance with kidney inflammation and injury. MicroRNAs are emerged as key regulators of insulin signaling. Morin has insulin-mimetic effect with the improvement of insulin resistance and kidney injury. This study investigated the protective mechanisms of morin against fructose-induced kidney injury, with particular focus on miR-330 expression change, inflammatory response, and insulin signaling impairment. miR-330, sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR)1/3 signaling, nuclear factor-κB (NF-κB)/NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, and insulin signaling were detected in kidney cortex of fructose-fed rats and fructose-exposed HK-2 cells, respectively. Whether miR-330 mediated inflammatory response to affect insulin signaling was examined using SphK1 inhibitor, S1PR1/3 short interfering RNA, or miR-330 mimic/inhibitor, respectively. Fructose was found to downregulate miR-330 expression to increase SphK1/S1P/S1PR1/3 signaling, and then activate NF-κB/NLRP3 inflammasome to produce IL-1β, causing insulin signaling impairment. Moreover, morin upregulated miR-330 and partly attenuated inflammatory response and insulin signaling impairment to alleviate kidney injury. These findings suggest that morin protects against fructose-induced kidney insulin signaling impairment by upregulating miR-330 to reduce inflammatory response. Morin may be a potential therapeutic agent for the treatment of kidney injury associated with fructose-induced inflammation and insulin signaling impairment. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Renal transplantation induces mitochondrial uncoupling, increased kidney oxygen consumption, and decreased kidney oxygen tension.

PubMed

Papazova, Diana A; Friederich-Persson, Malou; Joles, Jaap A; Verhaar, Marianne C

2015-01-01

Hypoxia is an acknowledged pathway to renal injury and ischemia-reperfusion (I/R) and is known to reduce renal oxygen tension (Po2). We hypothesized that renal I/R increases oxidative damage and induces mitochondrial uncoupling, resulting in increased oxygen consumption and hence kidney hypoxia. Lewis rats underwent syngenic renal transplantation (TX) and contralateral nephrectomy. Controls were uninephrectomized (1K-CON) or left untreated (2K-CON). After 7 days, urinary excretion of protein and thiobarbituric acid-reactive substances were measured, and after 14 days glomerular filtration rate (GFR), renal blood flow, whole kidney Qo2, cortical Po2, kidney cortex mitochondrial uncoupling, renal oxidative damage, and tubulointerstitial injury were assessed. TX, compared with 1K-CON, resulted in mitochondrial uncoupling mediated via uncoupling protein-2 (16 ± 3.3 vs. 0.9 ± 0.4 pmol O2 · s(-1)· mg protein(-1), P < 0.05) and increased whole kidney Qo2 (55 ± 16 vs. 33 ± 10 μmol O2/min, P < 0.05). Corticomedullary Po2 was lower in TX compared with 1K-CON (30 ± 13 vs. 47 ± 4 μM, P < 0.05) whereas no significant difference was observed between 2K-CON and 1K-CON rats. Proteinuria, oxidative damage, and the tubulointerstitial injury score were not significantly different in 1K-CON and TX. Treatment of donors for 5 days with mito-TEMPO reduced mitochondrial uncoupling but did not affect renal hemodynamics, Qo2, Po2, or injury. Collectively, our results demonstrate increased mitochondrial uncoupling as an early event after experimental renal transplantation associated with increased oxygen consumption and kidney hypoxia in the absence of increases in markers of damage. Copyright © 2015 the American Physiological Society.

Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats.

PubMed

Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

2016-12-20

The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured. Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups. Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.

Novel application of complementary imaging techniques to examine in vivo glucose metabolism in the kidney

PubMed Central

Hato, Takashi; Friedman, Allon N.; Mang, Henry; Plotkin, Zoya; Dube, Shataakshi; Hutchins, Gary D.; Territo, Paul R.; McCarthy, Brian P.; Riley, Amanda A.; Pichumani, Kumar; Malloy, Craig R.; Harris, Robert A.; Dagher, Pierre C.

2016-01-01

The metabolic status of the kidney is a determinant of injury susceptibility and a measure of progression for many disease processes; however, noninvasive modalities to assess kidney metabolism are lacking. In this study, we employed positron emission tomography (PET) and intravital multiphoton microscopy (MPM) to assess cortical and proximal tubule glucose tracer uptake, respectively, following experimental perturbations of kidney metabolism. Applying dynamic image acquisition PET with 2-18fluoro-2-deoxyglucose (18F-FDG) and tracer kinetic modeling, we found that an intracellular compartment in the cortex of the kidney could be distinguished from the blood and urine compartments in animals. Given emerging literature that the tumor suppressor protein p53 is an important regulator of cellular metabolism, we demonstrated that PET imaging was able to discern a threefold increase in cortical 18F-FDG uptake following the pharmacological inhibition of p53 in animals. Intravital MPM with the fluorescent glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) provided increased resolution and corroborated these findings at the level of the proximal tubule. Extending our observation of p53 inhibition on proximal tubule glucose tracer uptake, we demonstrated by intravital MPM that pharmacological inhibition of p53 diminishes mitochondrial potential difference. We provide additional evidence that inhibition of p53 alters key metabolic enzymes regulating glycolysis and increases intermediates of glycolysis. In summary, we provide evidence that PET is a valuable tool for examining kidney metabolism in preclinical and clinical studies, intravital MPM is a powerful adjunct to PET in preclinical studies of metabolism, and p53 inhibition alters basal kidney metabolism. PMID:26764206

Modulation of renal oxygenation and perfusion in rat kidney monitored by quantitative diffusion and blood oxygen level dependent magnetic resonance imaging on a clinical 1.5T platform.

PubMed

Jerome, Neil P; Boult, Jessica K R; Orton, Matthew R; d'Arcy, James; Collins, David J; Leach, Martin O; Koh, Dow-Mu; Robinson, Simon P

2016-10-03

To investigate the combined use of intravoxel incoherent motion (IVIM) diffusion-weighted (DW) and blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) to assess rat renal function using a 1.5T clinical platform. Multiple b-value DW and BOLD MR images were acquired from adult rats using a parallel clinical coil arrangement, enabling quantitation of the apparent diffusion coefficient (ADC), IVIM-derived diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f), and the transverse relaxation time T 2 *, for whole kidney, renal cortex, and medulla. Following the acquisition of two baseline datasets to assess measurement repeatability, images were acquired following i.v. administration of hydralazine, furosemide, or angiotensin II for up to 40 min. Excellent repeatability (CoV <10 %) was observed for ADC, D, f and T 2 * measured over the whole kidney. Hydralazine induced a marked and significant (p < 0.05) reduction in whole kidney ADC, D, and T 2 *, and a significant (p < 0.05) increase in D* and f. Furosemide significantly (p < 0.05) increased whole kidney ADC, D, and T 2 *. A more variable response to angiotensin II was determined, with a significant (p < 0.05) increase in medulla D* and significant (p < 0.05) reduction in whole kidney T 2 * established. Multiparametric MRI, incorporating quantitation of IVIM DWI and BOLD biomarkers and performed on a clinical platform, can be used to monitor the acute effects of vascular and tubular modulating drugs on rat kidney function in vivo. Clinical adoption of such functional imaging biomarkers can potentially inform on treatment effects in patients with renal dysfunction.

How instructions modify perception: An fMRI study investigating brain areas involved in attributing human agency

PubMed Central

Stanley, James; Gowen, Emma; Miall, R. Christopher

2010-01-01

Behavioural studies suggest that the processing of movement stimuli is influenced by beliefs about the agency behind these actions. The current study examined how activity in social and action related brain areas differs when participants were instructed that identical movement stimuli were either human or computer generated. Participants viewed a series of point-light animation figures derived from motion-capture recordings of a moving actor, while functional magnetic resonance imaging (fMRI) was used to monitor patterns of neural activity. The stimuli were scrambled to produce a range of stimulus realism categories; furthermore, before each trial participants were told that they were about to view either a recording of human movement or a computer-simulated pattern of movement. Behavioural results suggested that agency instructions influenced participants' perceptions of the stimuli. The fMRI analysis indicated different functions within the paracingulate cortex: ventral paracingulate cortex was more active for human compared to computer agency instructed trials across all stimulus types, whereas dorsal paracingulate cortex was activated more highly in conflicting conditions (human instruction, low realism or vice versa). These findings support the hypothesis that ventral paracingulate encodes stimuli deemed to be of human origin, whereas dorsal paracingulate cortex is involved more in the ascertainment of human or intentional agency during the observation of ambiguous stimuli. Our results highlight the importance of prior instructions or beliefs on movement processing and the role of the paracingulate cortex in integrating prior knowledge with bottom-up stimuli. PMID:20398769

Whole kidney engineering for clinical translation.

PubMed

Kim, Ick-Hee; Ko, In Kap; Atala, Anthony; Yoo, James J

2015-04-01

Renal transplantation is currently the only definitive treatment for end-stage renal disease; however, this treatment is severely limited by the shortage of implantable kidneys. To address this shortcoming, development of an engineered, transplantable kidney has been proposed. Although current advances in engineering kidneys based on decellularization and recellularization techniques have offered great promises for the generation of functional kidney constructs, most studies have been conducted using rodent kidney constructs and short-term in-vivo evaluation. Toward clinical translations of this technique, several limitations need to be addressed. Human-sized renal scaffolds are desirable for clinical application, and the fabrication is currently feasible using native porcine and discarded human kidneys. Current progress in stem cell biology and cell culture methods have demonstrated feasibility of the use of embryonic stem cells, induced pluripotent stem cells, and primary renal cells as clinically relevant cell sources for the recellularization of renal scaffolds. Finally, approaches to long-term implantation of engineered kidneys are under investigation using antithrombogenic strategies such as functional reendothelialization of acellular kidney matrices. In the field of bioengineering, whole kidneys have taken a number of important initial steps toward clinical translations, but many challenges must be addressed to achieve a successful treatment for the patient with end-stage renal disease.

Pakistan's kidney trade: an overview of the 2007 'Transplantation of Human Organs and Human Tissue Ordinance.' To what extent will it curb the trade?

PubMed

Raza, Mohsen; Skordis-Worrall, Jolene

2012-01-01

Pakistan has the unenviable reputation for being one of the world's leading 'transplant tourism' destinations, largely the buying and selling of kidneys from its impoverished population to rich international patients. After nearly two decades of pressure to formally prohibit the trade, the Government of Pakistan promulgated the 'Transplantation of Human Organs and Human Tissue Ordinance' (THOTO) in 2007. This was then passed by Senate and enshrined in law in March 2010. This paper gives a brief overview of the organ trade within Pakistan and analyses the criteria of THOTO in banning the widespread practise. It then goes on to answer: 'To what extent will THOTO succeed in curbing Pakistan's kidney trade?' This is aided by the use of a comparative case study looking at India's failed organ trade legislation. This paper concludes THOTO has set a strong basis for curbing Pakistan's kidney trade. However, for this to be successfully achieved, it needs to be implemented with strong and sustained political will, strict and efficient enforcement as well as effective monitoring and evaluation. Efforts are needed to tackle both 'supply' and 'demand' factors of Pakistan's kidney trade, with developed countries also having a responsibility to reduce the flow of citizens travelling to Pakistan to purchase a kidney.

[Human positron emission tomography with oral 11C-vinpocetine].

PubMed

Vas, Adám; Christer, Halldin; Sóvágó, Judit; Johan, Sandell; Cselényi, Zsolt; Kiss, Béla; Kárpáti, Egon; Lars, Farde; Gulyás, Balázs

2003-11-16

Positron emission tomography (PET) is a useful tool for the investigation of certain physiological changes and for the evaluation of the distribution, and receptor binding of drugs labelled with positron emitting isotopes. Vinpocetine (ethyl-apovincaminate) is a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases. In the clinical practice vinpocetine is usually administered to the patients in intravenous infusion followed by long-term oral treatment. Until presently human data describing vinpocetine's kinetics and brain distribution came from ex vivo (blood, plasma, liquor) and post mortem (brain autoradiography) measurements. The authors wished to investigate the kinetics and distribution of vinpocetine in the brain and body after oral administration with PET in order to prove, that PET is useful in the non-invasive in vivo determination of these parameters. Vinpocetine was labelled with carbon-11 and the radioactivity was measured by PET in the stomach, liver, brain, colon and kidneys in healthy male volunteers. The radioactivity in the blood and urine was also determined. After oral administration, [11C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the oral administration of the labelled drug (average maximum uptake: 0.7% of the administered total dose). Brain distribution was heterogeneous (with preferences in the thalamus, basal ganglia and occipital cortex), similar to the distribution previously reported by the authors after intravenous administration. Vinpocetine, administered orally to human volunteers, readily entered the bloodstream from the stomach and the gastrointestinal tract and thereafter passed the blood-brain barrier and entered the brain. Radioactivity from [11C]vinpocetine was also demonstrated in the kidneys and in urine. The study demonstrates that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally administered labelled drugs active in the central nervous system in the living human body.

Ventral-Dorsal Functional Contribution of the Posterior Cingulate Cortex in Human Spatial Orientation: A Meta-Analysis.

PubMed

Burles, Ford; Umiltá, Alberto; McFarlane, Liam H; Potocki, Kendra; Iaria, Giuseppe

2018-01-01

The retrosplenial cortex has long been implicated in human spatial orientation and navigation. However, neural activity peaks labeled "retrosplenial cortex" in human neuroimaging studies investigating spatial orientation often lie significantly outside of the retrosplenial cortex proper. This has led to a large and anatomically heterogenous region being ascribed numerous roles in spatial orientation and navigation. Here, we performed a meta-analysis of functional Magnetic Resonance Imaging (fMRI) investigations of spatial orientation and navigation and have identified a ventral-dorsal functional specialization within the posterior cingulate for spatial encoding vs. spatial recall . Generally, ventral portions of the posterior cingulate cortex were more likely to be activated by spatial encoding , i.e., passive viewing of scenes or active navigation without a demand to respond, perform a spatial computation, or localize oneself in the environment. Conversely, dorsal portions of the posterior cingulate cortex were more likely to be activated by cognitive demands to recall spatial information or to produce judgments of distance or direction to non-visible locations or landmarks. The greatly varying resting-state functional connectivity profiles of the ventral (centroids at MNI -22, -60, 6 and 20, -56, 6) and dorsal (centroid at MNI 4, -60, 28) posterior cingulate regions identified in the meta-analysis supported the conclusion that these regions, which would commonly be labeled as "retrosplenial cortex," should be more appropriately referred to as distinct subregions of the posterior cingulate cortex. We suggest that future studies investigating the role of the retrosplenial and posterior cingulate cortex in spatial tasks carefully localize activity in the context of these identifiable subregions.

The bovine kidney as an experimental model in urology: external gross anatomy.

PubMed

Carvalho, Francismar S; Bagetti Filho, Hélio J S; Henry, Robert W; Pereira-Sampaio, Marco A

2009-01-01

The objective of this work was to obtain and record detailed and accurate measurements of the bovine kidney and to compare these new data with findings in humans. Thirty-eight bovine kidneys were used. The total number of lobes, along with the number of lobes located in the cranial polar, caudal polar and hilar regions, were recorded. Several measurements of the kidneys were made and evaluated. The hilar region presents the greatest length (mean of 76.87 mm) of the 3 renal regions of the kidney. The large area of the bovine renal hilus could make access to hilar structures easier than in the human kidney. The coefficient of variation for renal length was small (8.14%), while the coefficient of variation for the lobar number was high (26.82%). The number of renal lobes ranged from 13 to 35, with a mean of 20.62. The hilar region presents the highest number of lobes, while the cranial pole presents the lowest. The number of lobes in the cranial and caudal poles increases with the width of these regions. This is different from the hilar region, in which the lobar number increases with the length of the hilus. These data indicate that the adult bovine kidney can be used as a model for certain urologic procedures, but researchers must be aware that there are some major differences between the adult bovine kidney and the human kidney, as indicated by the data reported in this paper. (c) 2008 S. Karger AG, Basel.

Energy Constraints for Building Large-Scale Systems

DTIC Science & Technology

2016-03-17

power (and energy) constrained in their communication. The human cortex consumes about 20W of power, of which, only a fraction (< 25%) of this power...neurobiological systems use a similar approach in the fact that over 90% of neurons in cortex project locally to nearby neurons (i.e. nearest 1000 pyramidal...are constrained in their communication because of power constraints [1]. The human cortex consumes about 20W of power, of which, only a fraction (25

Spatially invariant coding of numerical information in functionally defined subregions of human parietal cortex.

PubMed

Eger, E; Pinel, P; Dehaene, S; Kleinschmidt, A

2015-05-01

Macaque electrophysiology has revealed neurons responsive to number in lateral (LIP) and ventral (VIP) intraparietal areas. Recently, fMRI pattern recognition revealed information discriminative of individual numbers in human parietal cortex but without precisely localizing the relevant sites or testing for subregions with different response profiles. Here, we defined the human functional equivalents of LIP (feLIP) and VIP (feVIP) using neurophysiologically motivated localizers. We applied multivariate pattern recognition to investigate whether both regions represent numerical information and whether number codes are position specific or invariant. In a delayed number comparison paradigm with laterally presented numerosities, parietal cortex discriminated between numerosities better than early visual cortex, and discrimination generalized across hemifields in parietal, but not early visual cortex. Activation patterns in the 2 parietal regions of interest did not differ in the coding of position-specific or position-independent number information, but in the expression of a numerical distance effect which was more pronounced in feLIP. Thus, the representation of number in parietal cortex is at least partially position invariant. Both feLIP and feVIP contain information about individual numerosities in humans, but feLIP hosts a coarser representation of numerosity than feVIP, compatible with either broader tuning or a summation code. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The antioxidant silybin prevents high glucose-induced oxidative stress and podocyte injury in vitro and in vivo

PubMed Central

Khazim, Khaled; Gorin, Yves; Cavaglieri, Rita Cassia; Abboud, Hanna E.

2013-01-01

Podocyte injury, a major contributor to the pathogenesis of diabetic nephropathy, is caused at least in part by the excessive generation of reactive oxygen species (ROS). Overproduction of superoxide by the NADPH oxidase isoform Nox4 plays an important role in podocyte injury. The plant extract silymarin is attributed antioxidant and antiproteinuric effects in humans and in animal models of diabetic nephropathy. We investigated the effect of silybin, the active constituent of silymarin, in cultures of mouse podocytes and in the OVE26 mouse, a model of type 1 diabetes mellitus and diabetic nephropathy. Exposure of podocytes to high glucose (HG) increased 60% the intracellular superoxide production, 90% the NADPH oxidase activity, 100% the Nox4 expression, and 150% the number of apoptotic cells, effects that were completely blocked by 10 μM silybin. These in vitro observations were confirmed by similar in vivo findings. The kidney cortex of vehicle-treated control OVE26 mice displayed greater Nox4 expression and twice as much superoxide production than cortex of silybin-treated mice. The glomeruli of control OVE26 mice displayed 35% podocyte drop out that was not present in the silybin-treated mice. Finally, the OVE26 mice experienced 54% more pronounced albuminuria than the silybin-treated animals. In conclusion, this study demonstrates a protective effect of silybin against HG-induced podocyte injury and extends this finding to an animal model of diabetic nephropathy. PMID:23804455

Protective effect of adipose-derived mesenchymal stem cells against acute kidney injury induced by ischemia-reperfusion in Sprague-Dawley rats.

PubMed

Sheashaa, Hussein; Lotfy, Ahmed; Elhusseini, Fatma; Aziz, Azza Abdel; Baiomy, Azza; Awad, Samah; Alsayed, Aziza; El-Gilany, Abdel-Hady; Saad, Mohamed-Ahdy A A; Mahmoud, Khaled; Zahran, Faten; Salem, Dalia A; Sarhan, Ahmed; Ghaffar, Hassan Abdel; Sobh, Mohamed

2016-05-01

Acute kidney injury (AKI) is a complex clinical condition associated with significant morbidity and mortality and lacking effective management. Ischemia-reperfusion injury (IRI) remains one of the leading causes of AKI in native and transplanted kidneys. The aim of this study was to evaluate the efficacy of adipose-derived mesenchymal stem cells (ADSCs) in the prevention of renal IRI in rats. The study was conducted on male Sprague-Dawley rats (n=72) weighing 250-300 g. Rats were randomly assigned to three main groups: i) Sham-operated control group (n=24); ii) positive control group, in which rats were subjected to IRI and were administered culture media following 4 h of IRI (n=24); and iii) ADSC group (n=24), in which rats were administered 1×10 6 ADSCs via the tail vein following 4 h of IRI. Each main group was further divided according to the timing after IRI into four equal-sized subgroups. Renal function was tested via the measurement of serum creatinine levels and creatinine clearance. In addition, malondialdehyde (MDA) levels were determined in serum and renal tissue homogenate as an indicator of oxidative stress. Histopathological changes were analyzed in different regions of the kidney, namely the cortex, outer stripe of the outer medulla (OSOM), inner stripe of the outer medulla (ISOM) and inner medulla. In each region, the scoring system considered active injury changes, regenerative changes and chronic changes. The ADSCs were assessed and their differentiation capability was verified. IRI resulted in a significant increase in serum creatinine, serum and tissue MDA levels and a significant reduction in creatinine clearance compared with those in sham-operated rats,. These changes were attenuated by the use of ADSCs. The prominent histopathological changes in the cortex, ISOM and OSOM were reflected in the injury score, which was significantly evident in the positive control group. The use of ADSCs was associated with significantly lowered injury scores at days 1 and 3; however, no significant effect was observed on day 7. These results indicate that the use of ADSCs ameliorates renal injury and dysfunction associated with IRI in rats.

Production and actions of superoxide in the renal medulla.

PubMed

Zou, A P; Li, N; Cowley, A W

2001-02-01

The present study characterized the biochemical pathways responsible for superoxide (O(2)(-.)) production in different regions of the rat kidney and determined the role of O(2)(-.)in the control of renal medullary blood flow (MBF) and renal function. By use of dihydroethidium/DNA fluorescence spectrometry with microtiter plates, the production of O(2)(-. )was monitored when tissue homogenate from different kidney regions was incubated with substrates for the major O(2)(-.)-producing enzymes, such as NADH/NADPH oxidase, xanthine oxidase, and mitochondrial respiratory chain enzymes. The production of O(2)(-. )via NADH oxidase was greater (P<0.05) in the renal cortex and outer medulla (OM) than in the papilla. The mitochondrial enzyme activity for O(2)(-.)production was higher (P<0.05) in the OM than in the cortex and papilla. Compared with NADH oxidase and mitochondrial enzymes, xanthine oxidase and NADPH oxidase produced much less O(2)(-. )in the kidney under this condition. Overall, the renal OM exhibited the greatest enzyme activities for O(2)(-.)production. In anesthetized rats, renal medullary interstitial infusion of a superoxide dismutase inhibitor, diethyldithiocarbamate, markedly decreased renal MBF and sodium excretion. Diethyldithiocarbamate (5 mg/kg per minute by renal medullary interstitial infusion [RI]) reduced the renal medullary laser-Doppler flow signal from 0.6+/-0.04 to 0.4+/-0.03 V, a reduction of 33%, and both urine flow and sodium excretion decreased by 49%. In contrast, a membrane-permeable superoxide dismutase mimetic, 4-hydroxytetramethyl-piperidine-1-oxyl (TEMPOL, 30 micromol/kg per minute RI) increased MBF and sodium excretion by 34% and 69%, respectively. These effects of TEMPOL on renal MBF and sodium excretion were not altered by pretreatment with N(G)-nitro-L-arginine methyl ester (10 microgram/kg per minute RI). We conclude that (1) renal medullary O(2)(-. )is primarily produced in the renal OM; (2) both NADH oxidase and mitochondrial enzymes are responsible for the O(2)(-.)production in this kidney region; and (3) O(2)(-. )exerts a tonic regulatory action on renal MBF.

The relationship between cadmium in kidney and cadmium in urine and blood in an environmentally exposed population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akerstrom, Magnus, E-mail: magnus.akerstrom@amm.gu.se; Barregard, Lars; Lundh, Thomas

Introduction: Cadmium (Cd) is toxic to the kidney and a major part of the body burden occurs here. Cd in urine (U-Cd) and blood (B-Cd) are widely-used biomarkers for assessing Cd exposure or body burden. However, empirical general population data on the relationship between Cd in kidney (K-Cd), urine, and blood are scarce. Our objectives were to determine the relationship between cadmium in kidney, urine, and blood, and calculate the elimination half-time of Cd from the kidney. Methods: Kidney cortex biopsies, urine, and blood samples were collected from 109 living kidney donors. Cd concentrations were determined and the relationships betweenmore » K-Cd, U-Cd, and B-Cd were investigated in regression models. The half-time of K-Cd was estimated from the elimination constant. Results: There was a strong association between K-Cd and U-Cd adjusted for creatinine (r{sub p} = 0.70, p < 0.001), while the association with B-Cd was weaker (r{sub p} = 0.44, p < 0.001). The relationship between K-Cd and U-Cd was nonlinear, with slower elimination of Cd at high K-Cd. Estimates of the K-Cd half-time varied between 18 and 44 years. A K-Cd of 25 μg/g corresponds to U-Cd of 0.42 μg/g creatinine in overnight urine (U-Cd/K-Cd ratio: about 1:60). Multivariate models showed Cd in blood and urinary albumin as determinants for U-Cd excretion. Discussion: In healthy individuals with low-level Cd exposure, there was a strong correlation between Cd in kidney and urine, especially after adjustment for creatinine. Urinary Cd was also affected by Cd in blood and urinary albumin. Previous estimates of the U-Cd/K-Cd ratio may underestimate K-Cd at low U-Cd. - Highlights: ► The first study of the relation between Cd in kidney, blood and urine at low U-Cd ► Simultaneous samples were collected from healthy kidney donors. ► There was a nonlinear relationship between cadmium in kidney and urine. ► Estimates of the kidney cadmium half-time were 18–44 years, depending on model used. ► Previous data seem to underestimate kidney cadmium at low urinary cadmium.« less

Targeted Nanoparticles for Kidney Cancer Therapy

DTIC Science & Technology

2013-10-01

AD_________________ Award Number: W81XWH-10-1-0434 TITLE: Targeted Nanoparticles for Kidney Cancer Therapy PRINCIPAL...Targeted Nanoparticles for Kidney Cancer Therapy 5b. GRANT NUMBER W81XWH-10-1-0434 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...lines following treatment with D5 nanotubes. Tthermoablation will be studied initially. Human kidney cancer cells will be injected into the kidney

The Evolution of Human Handedness

PubMed Central

Smaers, Jeroen B; Steele, James; Case, Charleen R; Amunts, Katrin

2013-01-01

There is extensive evidence for an early vertebrate origin of lateralized motor behavior and of related asymmetries in underlying brain systems. We investigate human lateralized motor functioning in a broad comparative context of evolutionary neural reorganization. We quantify evolutionary trends in the fronto-cerebellar system (involved in motor learning) across 46 million years of divergent primate evolution by comparing rates of evolution of prefrontal cortex, frontal motor cortex, and posterior cerebellar hemispheres along individual branches of the primate tree of life. We provide a detailed evolutionary model of the neuroanatomical changes leading to modern human lateralized motor functioning, demonstrating an increased role for the fronto-cerebellar system in the apes dating to their evolutionary divergence from the monkeys (∼30 million years ago (Mya)), and a subsequent shift toward an increased role for prefrontal cortex over frontal motor cortex in the fronto-cerebellar system in the Homo-Pan ancestral lineage (∼10 Mya) and in the human ancestral lineage (∼6 Mya). We discuss these results in the context of cortico-cerebellar functions and their likely role in the evolution of human tool use and speech. PMID:23647442

Human cortical–hippocampal dialogue in wake and slow-wave sleep

PubMed Central

Mitra, Anish; Hacker, Carl D.; Pahwa, Mrinal; Tagliazucchi, Enzo; Laufs, Helmut; Leuthardt, Eric C.; Raichle, Marcus E.

2016-01-01

Declarative memory consolidation is hypothesized to require a two-stage, reciprocal cortical–hippocampal dialogue. According to this model, higher frequency signals convey information from the cortex to hippocampus during wakefulness, but in the reverse direction during slow-wave sleep (SWS). Conversely, lower-frequency activity propagates from the information “receiver” to the “sender” to coordinate the timing of information transfer. Reversal of sender/receiver roles across wake and SWS implies that higher- and lower-frequency signaling should reverse direction between the cortex and hippocampus. However, direct evidence of such a reversal has been lacking in humans. Here, we use human resting-state fMRI and electrocorticography to demonstrate that δ-band activity and infraslow activity propagate in opposite directions between the hippocampus and cerebral cortex. Moreover, both δ activity and infraslow activity reverse propagation directions between the hippocampus and cerebral cortex across wake and SWS. These findings provide direct evidence for state-dependent reversals in human cortical–hippocampal communication. PMID:27791089

Theta Oscillations Rapidly Convey Odor-Specific Content in Human Piriform Cortex.

PubMed

Jiang, Heidi; Schuele, Stephan; Rosenow, Joshua; Zelano, Christina; Parvizi, Josef; Tao, James X; Wu, Shasha; Gottfried, Jay A

2017-04-05

Olfactory oscillations are pervasive throughout vertebrate and invertebrate nervous systems. Such observations have long implied that rhythmic activity patterns play a fundamental role in odor coding. Using intracranial EEG recordings from rare patients with medically resistant epilepsy, we find that theta oscillations are a distinct electrophysiological signature of olfactory processing in the human brain. Across seven patients, odor stimulation enhanced theta power in human piriform cortex, with robust effects at the level of single trials. Importantly, classification analysis revealed that piriform oscillatory activity conveys olfactory-specific information that can be decoded within 110-518 ms of a sniff, and maximally within the theta frequency band. This temporal window was also associated with increased theta-specific phase coupling between piriform cortex and hippocampus. Together these findings suggest that human piriform cortex has access to olfactory content in the time-frequency domain and can utilize these signals to rapidly differentiate odor stimuli. Copyright © 2017 Elsevier Inc. All rights reserved.

Urine biomarkers informative of human kidney allograft rejection and tolerance.

PubMed

Nissaisorakarn, Voravech; Lee, John Richard; Lubetzky, Michelle; Suthanthiran, Manikkam

2018-05-01

We developed urinary cell messenger RNA (mRNA) profiling to monitor in vivo status of human kidney allografts based on our conceptualization that the kidney allograft may function as an in vivo flow cell sorter allowing access of graft infiltrating cells to the glomerular ultrafiltrate and that interrogation of urinary cells is informative of allograft status. For the profiling urinary cells, we developed a two-step preamplification enhanced real-time quantitative PCR (RT-QPCR) assays with a customized amplicon; preamplification compensating for the low RNA yield from urine and the customized amplicon facilitating absolute quantification of mRNA and overcoming the inherent limitations of relative quantification widely used in RT-QPCR assays. Herein, we review our discovery and validation of urinary cell mRNAs as noninvasive biomarkers prognostic and diagnostic of acute cellular rejection (ACR) in kidney allografts. We summarize our results reflecting the utility of urinary cell mRNA profiling for predicting reversal of ACR with anti-rejection therapy; differential diagnosis of kidney allograft dysfunction; and noninvasive diagnosis and prognosis of BK virus nephropathy. Messenger RNA profiles associated with human kidney allograft tolerance are also summarized in this review. Altogether, data supporting the idea that urinary cell mRNA profiles are informative of kidney allograft status and tolerance are reviewed in this report. Copyright © 2018. Published by Elsevier Inc.

Fasting upregulates adipose triglyceride lipase and hormone-sensitive lipase levels and phosphorylation in mouse kidney.

PubMed

Marvyn, Phillip M; Bradley, Ryan M; Button, Emily B; Mardian, Emily B; Duncan, Robin E

2015-06-01

Circulating non-esterified fatty acids (NEFA) rise during fasting and are taken up by the kidneys, either directly from the plasma or during re-uptake of albumin from glomerular filtrate, and are stored as triacylglycerol (TAG). Subsequent utilization of stored fatty acids requires their hydrolytic release from cellular lipid droplets, but relatively little is known about renal lipolysis. We found that total [(3)H]triolein hydrolase activity of kidney lysates was significantly increased by 15% in the fasted state. Adipose triglyceride lipase (Atgl) and hormone-sensitive lipase (Hsl) mRNA expression was time-dependently increased by fasting, along with other fatty acid metabolism genes (Pparα, Cd36, and Aox). ATGL and HSL protein levels were also significantly induced (by 239 ± 7% and 322 ± 8%, respectively). Concomitant with changes in total protein levels, there was an increase in ATGL phosphorylation at the AMPK-regulated serine 406 site in the 14-3-3 binding motif, and an increase in HSL phosphorylation at serines 565 and 660 that are regulated by AMPK and PKA, respectively. Using immunofluorescence, we further demonstrate nearly ubiquitous expression of ATGL in the renal cortex with a concentration on the apical/lumenal surface of some cortical tubules. Our findings suggest a role for ATGL and HSL in kidney lipolysis.

Histopathological analysis for osteomalacia and tubulopathy in itai-itai disease.

PubMed

Baba, Hayato; Tsuneyama, Koichi; Kumada, Tokimasa; Aoshima, Keiko; Imura, Johji

2014-02-01

Cadmium (Cd) is a widespread environmental contaminant that causes both renal tubulopathy and osteomalacia. Osteomalacia is thought to be a result of renal tubulopathy, but there are few studies about the histopathological relationship between the two pathoses. Therefore, in the present study, we examined specimens from cases of itai-itai disease (IID), the most severe form of chronic cadmium poisoning, to evaluate the relationship between them. We analyzed kidney and bone specimens of 61 IID cases and the data regarding Cd concentration in kidney and bone. Tubulopathy was graded on the basis of a three-step scale (mild, moderate, and severe) using the following three items: the degree of proximal tubular defluxion, thickness of renal cortex, and weight of the kidney. Osteomalacia was evaluated using the relative osteoid volume (ROV). There were 15 cases of mild, 19 cases of moderate, and 27 cases of severe tubulopathy. The average ROV was 24.9 ± 2.0%. ROV tended to increase as tubulopathy advanced in severity, and ROV was significantly higher in cases with severe tubulopathy than those with mild or moderate tubulopathy. ROV had a negative correlation with Cd concentration in the kidney but no correlation with that in the bone. Our results suggest that the development of osteomalacia was related to the development of tubulopathy.

Soft 3D-Printed Phantom of the Human Kidney with Collecting System.

PubMed

Adams, Fabian; Qiu, Tian; Mark, Andrew; Fritz, Benjamin; Kramer, Lena; Schlager, Daniel; Wetterauer, Ulrich; Miernik, Arkadiusz; Fischer, Peer

2017-04-01

Organ models are used for planning and simulation of operations, developing new surgical instruments, and training purposes. There is a substantial demand for in vitro organ phantoms, especially in urological surgery. Animal models and existing simulator systems poorly mimic the detailed morphology and the physical properties of human organs. In this paper, we report a novel fabrication process to make a human kidney phantom with realistic anatomical structures and physical properties. The detailed anatomical structure was directly acquired from high resolution CT data sets of human cadaveric kidneys. The soft phantoms were constructed using a novel technique that combines 3D wax printing and polymer molding. Anatomical details and material properties of the phantoms were validated in detail by CT scan, ultrasound, and endoscopy. CT reconstruction, ultrasound examination, and endoscopy showed that the designed phantom mimics a real kidney's detailed anatomy and correctly corresponds to the targeted human cadaver's upper urinary tract. Soft materials with a tensile modulus of 0.8-1.5 MPa as well as biocompatible hydrogels were used to mimic human kidney tissues. We developed a method of constructing 3D organ models from medical imaging data using a 3D wax printing and molding process. This method is cost-effective means for obtaining a reproducible and robust model suitable for surgical simulation and training purposes.

Human polyomavirus 9 in immunocompromised patients in the University Hospital in Hradec Kralove, Czech Republic.

PubMed

Fajfr, Miroslav; Pliskova, Lenka; Kutova, Radka; Matyskova-Kubisova, Michaela; Navratil, Pavel; Radocha, Jakub; Valenta, Zbynek; Dusilova-Sulkova, Sylvie

2017-12-01

Human polyomaviruses such as JC polyomavirus and BK polyomavirus have long been well known pathogens of immunocompromised patients. Several new members of this viral family have been described during the last decade. Human polyomavirus 9 seems to be a novel pathogen of transplanted patients according to some studies. The aim of our study was to determine the presence of human polyomavirus 9 in patients after kidney or stem cell transplantation (SCT) at the University Hospital in Hradec Kralove, Czech Republic. Overall 100 patients, 65 after kidney transplantation and 35 after SCT, were included into the study. At least three follow-up samples from each patient were examined for human polyomavirus 9 DNA presentation with the two previously described in-house PCR protocols. Despite the frequent reactivation of human CMV (14.3% in kidney transplantation and 63.3% after SCT) or BK polyomavirus in our patient group, there was no positivity for human polyomavirus 9 either in blood samples or urine samples. One of the possible reasons for this discrepancy versus previous published studies could be a relatively low proportion of patients treated by induction therapy before kidney transplantation in our study cohort. © 2017 Wiley Periodicals, Inc.

Characterization of diabetic nephropathy in CaM kinase IIalpha (Thr286Asp) transgenic mice.

PubMed

Suzuki, Hikari; Kato, Ichiro; Usui, Isao; Takasaki, Ichiro; Tabuchi, Yoshiaki; Oya, Takeshi; Tsuneyama, Koichi; Kawaguchi, Hiroshi; Hiraga, Koichi; Takasawa, Shin; Okamoto, Hiroshi; Tobe, Kazuyuki; Sasahara, Masakiyo

2009-01-30

Detailed studies were performed on diabetic kidneys derived from transgenic mice overexpressing the mutant form (Thr286Asp) of Ca(2+)/calmodulin-dependent protein kinase IIalpha (CaM kinase IIalpha) in pancreatic beta-cells. Kidney weight/body weight ratio, urinary albumin/creatinine ratio, serum BUN level, and mesangial/glomerular area ratio were all significantly higher in transgenic mice than in wild-type mice. cDNA microarray analysis revealed 17 up-regulated genes and 12 down-regulated genes in transgenic kidney. Among up-regulated genes, cyclin D2 (6.70-fold) and osteopontin (2.35-fold) were thought to play important roles in the progression of diabetic nephropathy. Transgenic glomeruli and tubular epithelial cells were strongly stained for osteopontin, a molecule which induces immune response. In quantitative real-time RT-PCR analyses, expressions of not only M1 macrophage marker genes but also M2 macrophage marker genes were elevated in renal cortex of transgenic mice. Overall results indicate that CaM kinase IIalpha (Thr286Asp) transgenic mice serve as an excellent model for diabetic nephropathy.

[Yersiniosis as a cause of acute tubulointerstitial nephritis and acute renal failure--case report].

PubMed

Runowski, Dariusz; Szymoniak, Norbert; Zaniew, Marcin; Piatkowska-Kopczyk, Małgorzata; Wozniak, Aldona; Kroll, Paweł; Zachwieja, Jacek

2005-01-01

Tubulointerstitial nephritis (TN) is a heterogenous disease, where disturbances of the interstitial tissue and renal tubules are found. Different immunological and nonimmunological mechanisms initiated by infectious and non-infectious factors may lead to TN. A case of 13-years-old girl with primary diagnosis of acute pyelonephritis is presented. The abdominal pain, headache, pain in lumbar region and intermittent fever with loss of appetite were observed in this girl a few weeks before admission. Microcytic anemia, proteinuria and glucosuria, azotemia and elevated markers of inflammatory response were found. In ultrasound examination heterogenous cortex echogenicity of both kidneys and disturbances in parenchymal blood flow were observed. In renal scintigraphy the discriminated catch index was found. Kidney biopsy revealed the edema of the interstitial space with mononuclear and lymphocyte infiltration. The diagnosis of TN was established upon the history, clinical examination, results of laboratory tests, kidney imaging and biopsy. After steroid and doxycycline treatment an improvement and normalization of the results of laboratory tests were observed. It seems to be justified to consider Yersinia infection as a cause of acute tubulointerstitial nephritis.

Role of Na+/K+-ATPase in Natriuretic Effect of Prolactin in a Model of Cholestasis of Pregnancy.

PubMed

Abramicheva, P A; Balakina, T A; Bulaeva, O A; Guseva, A A; Lopina, O D; Smirnova, O V

2017-05-01

Participation of Na+/K+-ATPase in the natriuretic effect of prolactin in a cholestasis of pregnancy model was investigated. The Na+/K+-ATPase activity in rat kidney medulla, where active sodium reabsorption occurs, decreased in the model of cholestasis of pregnancy and other hyperprolactinemia types compared with intact animals. This effect was not connected with the protein level of α1- and β-subunits of Na+/K+-ATPase measured by Western blotting in the kidney medulla. Decrease in Na+/K+-ATPase activity in the kidney cortex was not significant, as well as decrease in the quantity of mRNA and proteins of the α1- and β-subunits of Na+/K+-ATPase. There were no correlations between the Na+/K+-ATPase activity and sodium clearance, although sodium clearance increased significantly in the model of cholestasis of pregnancy and other hyperprolactinemia groups under conditions of stable glomerular filtration rate measured by creatinine clearance. We conclude that the Na+/K+-ATPase is not the only mediator of the natriuretic effect of prolactin in the model of cholestasis of pregnancy.

Tributyltin chloride induces renal dysfunction by inflammation and oxidative stress in female rats.

PubMed

Coutinho, João V S; Freitas-Lima, Leandro C; Freitas, Frederico F C T; Freitas, Flávia P S; Podratz, Priscila L; Magnago, Rafaella P L; Porto, Marcella L; Meyrelles, Silvana S; Vasquez, Elisardo C; Brandão, Poliane A A; Carneiro, Maria T W D; Paiva-Melo, Francisca D; Miranda-Alves, Leandro; Silva, Ian V; Gava, Agata L; Graceli, Jones B

2016-10-17

Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the Cortical Nephrogenic Niche of the Human and Mouse Kidney.

PubMed

Lindström, Nils O; Guo, Jinjin; Kim, Albert D; Tran, Tracy; Guo, Qiuyu; De Sena Brandine, Guilherme; Ransick, Andrew; Parvez, Riana K; Thornton, Matthew E; Basking, Laurence; Grubbs, Brendan; McMahon, Jill A; Smith, Andrew D; McMahon, Andrew P

2018-03-01

Cellular interactions among nephron, interstitial, and collecting duct progenitors drive mammalian kidney development. In mice, Six2 + nephron progenitor cells (NPCs) and Foxd1 + interstitial progenitor cells (IPCs) form largely distinct lineage compartments at the onset of metanephric kidney development. Here, we used the method for analyzing RNA following intracellular sorting (MARIS) approach, single-cell transcriptional profiling, in situ hybridization, and immunolabeling to characterize the presumptive NPC and IPC compartments of the developing human kidney. As in mice, each progenitor population adopts a stereotypical arrangement in the human nephron-forming niche: NPCs capped outgrowing ureteric branch tips, whereas IPCs were sandwiched between the NPCs and the renal capsule. Unlike mouse NPCs, human NPCs displayed a transcriptional profile that overlapped substantially with the IPC transcriptional profile, and key IPC determinants, including FOXD1 , were readily detected within SIX2 + NPCs. Comparative gene expression profiling in human and mouse Six2/SIX2 + NPCs showed broad agreement between the species but also identified species-biased expression of some genes. Notably, some human NPC-enriched genes, including DAPL1 and COL9A2 , are linked to human renal disease. We further explored the cellular diversity of mesenchymal cell types in the human nephrogenic niche through single-cell transcriptional profiling. Data analysis stratified NPCs into two main subpopulations and identified a third group of differentiating cells. These findings were confirmed by section in situ hybridization with novel human NPC markers predicted through the single-cell studies. This study provides a benchmark for the mesenchymal progenitors in the human nephrogenic niche and highlights species-variability in kidney developmental programs. Copyright © 2018 by the American Society of Nephrology.

Subtle Alterations in Brain Anatomy May Change an Individual’s Personality in Chronic Pain

PubMed Central

Gustin, Sylvia M.; McKay, Jamie G.; Petersen, Esben T.; Peck, Chris C.; Murray, Greg M.; Henderson, Luke A.

2014-01-01

It is well established that gross prefrontal cortex damage can affect an individual’s personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual’s personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual’s personality. PMID:25291361

Learning-dependent plasticity in human auditory cortex during appetitive operant conditioning.

PubMed

Puschmann, Sebastian; Brechmann, André; Thiel, Christiane M

2013-11-01

Animal experiments provide evidence that learning to associate an auditory stimulus with a reward causes representational changes in auditory cortex. However, most studies did not investigate the temporal formation of learning-dependent plasticity during the task but rather compared auditory cortex receptive fields before and after conditioning. We here present a functional magnetic resonance imaging study on learning-related plasticity in the human auditory cortex during operant appetitive conditioning. Participants had to learn to associate a specific category of frequency-modulated tones with a reward. Only participants who learned this association developed learning-dependent plasticity in left auditory cortex over the course of the experiment. No differential responses to reward predicting and nonreward predicting tones were found in auditory cortex in nonlearners. In addition, learners showed similar learning-induced differential responses to reward-predicting and nonreward-predicting tones in the ventral tegmental area and the nucleus accumbens, two core regions of the dopaminergic neurotransmitter system. This may indicate a dopaminergic influence on the formation of learning-dependent plasticity in auditory cortex, as it has been suggested by previous animal studies. Copyright © 2012 Wiley Periodicals, Inc.

Kidney damage in extracorporeal shock wave lithotripsy: a numerical approach for different shock profiles.

PubMed

Weinberg, Kerstin; Ortiz, Michael

2009-08-01

In shock-wave lithotripsy--a medical procedure to fragment kidney stones--the patient is subjected to hypersonic waves focused at the kidney stone. Although this procedure is widely applied, the physics behind this medical treatment, in particular the question of how the injuries to the surrounding kidney tissue arise, is still under investigation. To contribute to the solution of this problem, two- and three-dimensional numerical simulations of a human kidney under shock-wave loading are presented. For this purpose a constitutive model of the bio-mechanical system kidney is introduced, which is able to map large visco-elastic deformations and, in particular, material damage. The specific phenomena of cavitation induced oscillating bubbles is modeled here as an evolution of spherical pores within the soft kidney tissue. By means of large scale finite element simulations, we study the shock-wave propagation into the kidney tissue, adapt unknown material parameters and analyze the resulting stress states. The simulations predict localized damage in the human kidney in the same regions as observed in animal experiments. Furthermore, the numerical results suggest that in first instance the pressure amplitude of the shock wave impulse (and not so much its exact time-pressure profile) is responsible for damaging the kidney tissue.

The harmonic organization of auditory cortex

PubMed Central

Wang, Xiaoqin

2013-01-01

A fundamental structure of sounds encountered in the natural environment is the harmonicity. Harmonicity is an essential component of music found in all cultures. It is also a unique feature of vocal communication sounds such as human speech and animal vocalizations. Harmonics in sounds are produced by a variety of acoustic generators and reflectors in the natural environment, including vocal apparatuses of humans and animal species as well as music instruments of many types. We live in an acoustic world full of harmonicity. Given the widespread existence of the harmonicity in many aspects of the hearing environment, it is natural to expect that it be reflected in the evolution and development of the auditory systems of both humans and animals, in particular the auditory cortex. Recent neuroimaging and neurophysiology experiments have identified regions of non-primary auditory cortex in humans and non-human primates that have selective responses to harmonic pitches. Accumulating evidence has also shown that neurons in many regions of the auditory cortex exhibit characteristic responses to harmonically related frequencies beyond the range of pitch. Together, these findings suggest that a fundamental organizational principle of auditory cortex is based on the harmonicity. Such an organization likely plays an important role in music processing by the brain. It may also form the basis of the preference for particular classes of music and voice sounds. PMID:24381544

Spatial attention increases high-frequency gamma synchronisation in human medial visual cortex.

PubMed

Koelewijn, Loes; Rich, Anina N; Muthukumaraswamy, Suresh D; Singh, Krish D

2013-10-01

Visual information processing involves the integration of stimulus and goal-driven information, requiring neuronal communication. Gamma synchronisation is linked to neuronal communication, and is known to be modulated in visual cortex both by stimulus properties and voluntarily-directed attention. Stimulus-driven modulations of gamma activity are particularly associated with early visual areas such as V1, whereas attentional effects are generally localised to higher visual areas such as V4. The absence of a gamma increase in early visual cortex is at odds with robust attentional enhancements found with other measures of neuronal activity in this area. Here we used magnetoencephalography (MEG) to explore the effect of spatial attention on gamma activity in human early visual cortex using a highly effective gamma-inducing stimulus and strong attentional manipulation. In separate blocks, subjects tracked either a parafoveal grating patch that induced gamma activity in contralateral medial visual cortex, or a small line at fixation, effectively attending away from the gamma-inducing grating. Both items were always present, but rotated unpredictably and independently of each other. The rotating grating induced gamma synchronisation in medial visual cortex at 30-70 Hz, and in lateral visual cortex at 60-90 Hz, regardless of whether it was attended. Directing spatial attention to the grating increased gamma synchronisation in medial visual cortex, but only at 60-90 Hz. These results suggest that the generally found increase in gamma activity by spatial attention can be localised to early visual cortex in humans, and that stimulus and goal-driven modulations may be mediated at different frequencies within the gamma range. Copyright © 2013 Elsevier Inc. All rights reserved.

Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis.

PubMed

Lindström, Nils O; De Sena Brandine, Guilherme; Tran, Tracy; Ransick, Andrew; Suh, Gio; Guo, Jinjin; Kim, Albert D; Parvez, Riana K; Ruffins, Seth W; Rutledge, Elisabeth A; Thornton, Matthew E; Grubbs, Brendan; McMahon, Jill A; Smith, Andrew D; McMahon, Andrew P

2018-06-04

Mammalian nephrons arise from a limited nephron progenitor pool through a reiterative inductive process extending over days (mouse) or weeks (human) of kidney development. Here, we present evidence that human nephron patterning reflects a time-dependent process of recruitment of mesenchymal progenitors into an epithelial nephron precursor. Progressive recruitment predicted from high-resolution image analysis and three-dimensional reconstruction of human nephrogenesis was confirmed through direct visualization and cell fate analysis of mouse kidney organ cultures. Single-cell RNA sequencing of the human nephrogenic niche provided molecular insights into these early patterning processes and predicted developmental trajectories adopted by nephron progenitor cells in forming segment-specific domains of the human nephron. The temporal-recruitment model for nephron polarity and patterning suggested by direct analysis of human kidney development provides a framework for integrating signaling pathways driving mammalian nephrogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Caenorhabditis elegans as a model to study renal development and disease: sexy cilia.

PubMed

Barr, Maureen M

2005-02-01

The nematode Caenorhabditis elegans has no kidney per se, yet "the worm" has proved to be an excellent model to study renal-related issues, including tubulogenesis of the excretory canal, membrane transport and ion channel function, and human genetic diseases including autosomal dominant polycystic kidney disease (ADPKD). The goal of this review is to explain how C. elegans has provided insight into cilia development, cilia function, and human cystic kidney diseases.

Effects of long-term pre- and post-natal exposure to 2.45 GHz wireless devices on developing male rat kidney.

PubMed

Kuybulu, Ayça Esra; Öktem, Faruk; Çiriş, İbrahim Metin; Sutcu, Recep; Örmeci, Ahmet Rıfat; Çömlekçi, Selçuk; Uz, Efkan

2016-01-01

The aim of the present study was to investigate oxidative stress and apoptosis in kidney tissues of male Wistar rats that pre- and postnatally exposed to wireless electromagnetic field (EMF) with an internet frequency of 2.45 GHz for a long time. The study was conducted in three groups of rats which were pre-natal, post-natal. and sham exposed groups. Oxidative stress markers and histological evaluation of kidney tissues were studied. Renal tissue malondialdehyde (MDA) and total oxidant (TOS) levels of pre-natal group were high and total antioxidant (TAS) and superoxide dismutase (SOD) levels were low. Spot urine NAG/creatinine ratio was significantly higher in pre- and post-natal groups (p < 0.001). Tubular injury was detected in most of the specimens in post-natal groups. Immunohistochemical analysis showed low-intensity staining with Bax in cortex, high-intensity staining with Bcl-2 in cortical and medullar areas of pre-natal group (p values, 0.000, 0.002, 0.000, respectively) when compared with sham group. Bcl2/Bax staining intensity ratios of medullar and cortical area was higher in pre-natal group than sham group (p = 0.018, p = 0.011). Based on this study, it is thought that chronic pre- and post-natal period exposure to wireless internet frequency of EMF may cause chronic kidney damages; staying away from EMF source in especially pregnancy and early childhood period may reduce negative effects of exposure on kidney.

The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive.

PubMed

Goldman-Rakic, P S

1996-10-29

The functional architecture of prefrontal cortex is central to our understanding of human mentation and cognitive prowess. This region of the brain is often treated as an undifferentiated structure, on the one hand, or as a mosaic of psychological faculties, on the other. This paper focuses on the working memory processor as a specialization of prefrontal cortex and argues that the different areas within prefrontal cortex represent iterations of this function for different information domains, including spatial cognition, object cognition and additionally, in humans, semantic processing. According to this parallel processing architecture, the 'central executive' could be considered an emergent property of multiple domain-specific processors operating interactively. These processors are specializations of different prefrontal cortical areas, each interconnected both with the domain-relevant long-term storage sites in posterior regions of the cortex and with appropriate output pathways.

Midcingulate Motor Map and Feedback Detection: Converging Data from Humans and Monkeys

PubMed Central

Procyk, Emmanuel; Wilson, Charles R. E.; Stoll, Frederic M.; Faraut, Maïlys C. M.; Petrides, Michael; Amiez, Céline

2016-01-01

The functional and anatomical organization of the cingulate cortex across primate species is the subject of considerable and often confusing debate. The functions attributed to the midcingulate cortex (MCC) embrace, among others, feedback processing, pain, salience, action-reward association, premotor functions, and conflict monitoring. This multiplicity of functional concepts suggests either unresolved separation of functional contributions or integration and convergence. We here provide evidence from recent experiments in humans and from a meta-analysis of monkey data that MCC feedback-related activity is generated in the rostral cingulate premotor area by specific body maps directly related to the modality of feedback. As such, we argue for an embodied mechanism for adaptation and exploration in MCC. We propose arguments and precise tools to resolve the origins of performance monitoring signals in the medial frontal cortex, and to progress on issues regarding homology between human and nonhuman primate cingulate cortex. PMID:25217467

Mechanisms of migraine aura revealed by functional MRI in human visual cortex

PubMed Central

Hadjikhani, Nouchine; Sanchez del Rio, Margarita; Wu, Ona; Schwartz, Denis; Bakker, Dick; Fischl, Bruce; Kwong, Kenneth K.; Cutrer, F. Michael; Rosen, Bruce R.; Tootell, Roger B. H.; Sorensen, A. Gregory; Moskowitz, Michael A.

2001-01-01

Cortical spreading depression (CSD) has been suggested to underlie migraine visual aura. However, it has been challenging to test this hypothesis in human cerebral cortex. Using high-field functional MRI with near-continuous recording during visual aura in three subjects, we observed blood oxygenation level-dependent (BOLD) signal changes that demonstrated at least eight characteristics of CSD, time-locked to percept/onset of the aura. Initially, a focal increase in BOLD signal (possibly reflecting vasodilation), developed within extrastriate cortex (area V3A). This BOLD change progressed contiguously and slowly (3.5 ± 1.1 mm/min) over occipital cortex, congruent with the retinotopy of the visual percept. Following the same retinotopic progression, the BOLD signal then diminished (possibly reflecting vasoconstriction after the initial vasodilation), as did the BOLD response to visual activation. During periods with no visual stimulation, but while the subject was experiencing scintillations, BOLD signal followed the retinotopic progression of the visual percept. These data strongly suggest that an electrophysiological event such as CSD generates the aura in human visual cortex. PMID:11287655

Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip

PubMed Central

Musah, Samira; Mammoto, Akiko; Ferrante, Thomas C.; Jeanty, Sauveur S. F.; Hirano-Kobayashi, Mariko; Mammoto, Tadanori; Roberts, Kristen; Chung, Seyoon; Novak, Richard; Ingram, Miles; Fatanat-Didar, Tohid; Koshy, Sandeep; Weaver, James C.; Church, George M.; Ingber, Donald E.

2017-01-01

An in vitro model of the human kidney glomerulus — the major site of blood filtration — could facilitate drug discovery and illuminate kidney-disease mechanisms. Microfluidic organ-on-a-chip technology has been used to model the human proximal tubule, yet a kidney-glomerulus-on-a-chip has not been possible because of the lack of functional human podocytes — the cells that regulate selective permeability in the glomerulus. Here, we demonstrate an efficient (> 90%) and chemically defined method for directing the differentiation of human induced pluripotent stem (hiPS) cells into podocytes that express markers of the mature phenotype (nephrin+, WT1+, podocin+, Pax2−) and that exhibit primary and secondary foot processes. We also show that the hiPS-cell-derived podocytes produce glomerular basement-membrane collagen and recapitulate the natural tissue/tissue interface of the glomerulus, as well as the differential clearance of albumin and inulin, when co-cultured with human glomerular endothelial cells in an organ-on-a-chip microfluidic device. The glomerulus-on-a-chip also mimics adriamycin-induced albuminuria and podocyte injury. This in vitro model of human glomerular function with mature human podocytes may facilitate drug development and personalized-medicine applications. PMID:29038743

Word Recognition in Auditory Cortex

ERIC Educational Resources Information Center

DeWitt, Iain D. J.

2013-01-01

Although spoken word recognition is more fundamental to human communication than text recognition, knowledge of word-processing in auditory cortex is comparatively impoverished. This dissertation synthesizes current models of auditory cortex, models of cortical pattern recognition, models of single-word reading, results in phonetics and results in…

A computational model of cerebral cortex folding.

PubMed

Nie, Jingxin; Guo, Lei; Li, Gang; Faraco, Carlos; Stephen Miller, L; Liu, Tianming

2010-05-21

The geometric complexity and variability of the human cerebral cortex have long intrigued the scientific community. As a result, quantitative description of cortical folding patterns and the understanding of underlying folding mechanisms have emerged as important research goals. This paper presents a computational 3D geometric model of cerebral cortex folding initialized by MRI data of a human fetal brain and deformed under the governance of a partial differential equation modeling cortical growth. By applying different simulation parameters, our model is able to generate folding convolutions and shape dynamics of the cerebral cortex. The simulations of this 3D geometric model provide computational experimental support to the following hypotheses: (1) Mechanical constraints of the skull regulate the cortical folding process. (2) The cortical folding pattern is dependent on the global cell growth rate of the whole cortex. (3) The cortical folding pattern is dependent on relative rates of cell growth in different cortical areas. (4) The cortical folding pattern is dependent on the initial geometry of the cortex. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

The Neuropsychology of Ventral Prefrontal Cortex: Decision-Making and Reversal Learning

ERIC Educational Resources Information Center

Clark, L.; Cools, R.; Robbins, T. W.

2004-01-01

Converging evidence from human lesion, animal lesion, and human functional neuroimaging studies implicates overlapping neural circuitry in ventral prefrontal cortex in decision-making and reversal learning. The ascending 5-HT and dopamine neurotransmitter systems have a modulatory role in both processes. There is accumulating evidence that…

Development of the Human Cortex and the Concept of "Critical" or "Sensitive" Periods

ERIC Educational Resources Information Center

Uylings, H. B. M.

2006-01-01

This review describes the prenatal and postnatal development of the human cortex. Neurogenesis, neuronal migration, dendrite maturation, synaptogenesis, and white matter development are discussed. In addition, the concept of "critical" or "sensitive" periods is discussed as well as genetic and environmental influences (Nature-Nurture). The effects…

Functional and structural mapping of human cerebral cortex: Solutions are in the surfaces

PubMed Central

Van Essen, David C.; Drury, Heather A.; Joshi, Sarang; Miller, Michael I.

1998-01-01

The human cerebral cortex is notorious for the depth and irregularity of its convolutions and for its variability from one individual to the next. These complexities of cortical geography have been a chronic impediment to studies of functional specialization in the cortex. In this report, we discuss ways to compensate for the convolutions by using a combination of strategies whose common denominator involves explicit reconstructions of the cortical surface. Surface-based visualization involves reconstructing cortical surfaces and displaying them, along with associated experimental data, in various complementary formats (including three-dimensional native configurations, two-dimensional slices, extensively smoothed surfaces, ellipsoidal representations, and cortical flat maps). Generating these representations for the cortex of the Visible Man leads to a surface-based atlas that has important advantages over conventional stereotaxic atlases as a substrate for displaying and analyzing large amounts of experimental data. We illustrate this by showing the relationship between functionally specialized regions and topographically organized areas in human visual cortex. Surface-based warping allows data to be mapped from individual hemispheres to a surface-based atlas while respecting surface topology, improving registration of identifiable landmarks, and minimizing unwanted distortions. Surface-based warping also can aid in comparisons between species, which we illustrate by warping a macaque flat map to match the shape of a human flat map. Collectively, these approaches will allow more refined analyses of commonalities as well as individual differences in the functional organization of primate cerebral cortex. PMID:9448242

Functional and structural mapping of human cerebral cortex: solutions are in the surfaces

NASA Technical Reports Server (NTRS)

Van Essen, D. C.; Drury, H. A.; Joshi, S.; Miller, M. I.

1998-01-01

The human cerebral cortex is notorious for the depth and irregularity of its convolutions and for its variability from one individual to the next. These complexities of cortical geography have been a chronic impediment to studies of functional specialization in the cortex. In this report, we discuss ways to compensate for the convolutions by using a combination of strategies whose common denominator involves explicit reconstructions of the cortical surface. Surface-based visualization involves reconstructing cortical surfaces and displaying them, along with associated experimental data, in various complementary formats (including three-dimensional native configurations, two-dimensional slices, extensively smoothed surfaces, ellipsoidal representations, and cortical flat maps). Generating these representations for the cortex of the Visible Man leads to a surface-based atlas that has important advantages over conventional stereotaxic atlases as a substrate for displaying and analyzing large amounts of experimental data. We illustrate this by showing the relationship between functionally specialized regions and topographically organized areas in human visual cortex. Surface-based warping allows data to be mapped from individual hemispheres to a surface-based atlas while respecting surface topology, improving registration of identifiable landmarks, and minimizing unwanted distortions. Surface-based warping also can aid in comparisons between species, which we illustrate by warping a macaque flat map to match the shape of a human flat map. Collectively, these approaches will allow more refined analyses of commonalities as well as individual differences in the functional organization of primate cerebral cortex.

Renal cell carcinoma in a cat with polycystic kidney disease undergoing renal transplantation.

PubMed

Adams, Daniel J; Demchur, Jolie A; Aronson, Lillian R

2018-01-01

A 10-year-old spayed female American Shorthair cat underwent renal transplantation due to worsening chronic kidney disease secondary to polycystic kidney disease. During transplantation, the right kidney grossly appeared to be more diseased than the left and was firmly adhered to the surrounding tissues. An intraoperative fine-needle aspirate of the right native kidney revealed inflammatory cells but no evidence of neoplasia. To create space for the allograft, a right nephrectomy was performed. Following nephrectomy, the right native kidney was submitted for biopsy. Biopsy results revealed a renal cell carcinoma. Although the cat initially recovered well from surgery, delayed graft function was a concern in the early postoperative period. Significant azotemia persisted and the cat began to have diarrhea. Erythematous skin lesions developed in the perineal and inguinal regions, which were suspected to be secondary to thromboembolic disease based on histopathology. The cat's clinical status continued to decline with development of signs of sepsis, followed by marked obtundation with uncontrollable seizures. Given the postoperative diagnosis of renal cell carcinoma and the cat's progressively declining clinical status, humane euthanasia was elected. This case is the first to document renal cell carcinoma in a cat with polycystic kidney disease. An association of the two diseases has been reported in the human literature, but such a link has yet to be described in veterinary medicine. Given the association reported in the human literature, a plausible relationship between polycystic kidney disease and renal cell carcinoma in cats merits further investigation.

"Visual" Cortex of Congenitally Blind Adults Responds to Syntactic Movement.

PubMed

Lane, Connor; Kanjlia, Shipra; Omaki, Akira; Bedny, Marina

2015-09-16

Human cortex is comprised of specialized networks that support functions, such as visual motion perception and language processing. How do genes and experience contribute to this specialization? Studies of plasticity offer unique insights into this question. In congenitally blind individuals, "visual" cortex responds to auditory and tactile stimuli. Remarkably, recent evidence suggests that occipital areas participate in language processing. We asked whether in blindness, occipital cortices: (1) develop domain-specific responses to language and (2) respond to a highly specialized aspect of language-syntactic movement. Nineteen congenitally blind and 18 sighted participants took part in two fMRI experiments. We report that in congenitally blind individuals, but not in sighted controls, "visual" cortex is more active during sentence comprehension than during a sequence memory task with nonwords, or a symbolic math task. This suggests that areas of occipital cortex become selective for language, relative to other similar higher-cognitive tasks. Crucially, we find that these occipital areas respond more to sentences with syntactic movement but do not respond to the difficulty of math equations. We conclude that regions within the visual cortex of blind adults are involved in syntactic processing. Our findings suggest that the cognitive function of human cortical areas is largely determined by input during development. Human cortex is made up of specialized regions that perform different functions, such as visual motion perception and language processing. How do genes and experience contribute to this specialization? Studies of plasticity show that cortical areas can change function from one sensory modality to another. Here we demonstrate that input during development can alter cortical function even more dramatically. In blindness a subset of "visual" areas becomes specialized for language processing. Crucially, we find that the same "visual" areas respond to a highly specialized and uniquely human aspect of language-syntactic movement. These data suggest that human cortex has broad functional capacity during development, and input plays a major role in determining functional specialization. Copyright © 2015 the authors 0270-6474/15/3512859-10$15.00/0.

Contralateral cerebello-thalamo-cortical pathways with prominent involvement of associative areas in humans in vivo.

PubMed

Palesi, Fulvia; Tournier, Jacques-Donald; Calamante, Fernando; Muhlert, Nils; Castellazzi, Gloria; Chard, Declan; D'Angelo, Egidio; Wheeler-Kingshott, Claudia A M

2015-11-01

In addition to motor functions, it has become clear that in humans the cerebellum plays a significant role in cognition too, through connections with associative areas in the cerebral cortex. Classical anatomy indicates that neo-cerebellar regions are connected with the contralateral cerebral cortex through the dentate nucleus, superior cerebellar peduncle, red nucleus and ventrolateral anterior nucleus of the thalamus. The anatomical existence of these connections has been demonstrated using virus retrograde transport techniques in monkeys and rats ex vivo. In this study, using advanced diffusion MRI tractography we show that it is possible to calculate streamlines to reconstruct the pathway connecting the cerebellar cortex with contralateral cerebral cortex in humans in vivo. Corresponding areas of the cerebellar and cerebral cortex encompassed similar proportion (about 80%) of the tract, suggesting that the majority of streamlines passing through the superior cerebellar peduncle connect the cerebellar hemispheres through the ventrolateral thalamus with contralateral associative areas. This result demonstrates that this kind of tractography is a useful tool to map connections between the cerebellum and the cerebral cortex and moreover could be used to support specific theories about the abnormal communication along these pathways in cognitive dysfunctions in pathologies ranging from dyslexia to autism.

Asymmetric projections of the arcuate fasciculus to the temporal cortex underlie lateralized language function in the human brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takaya, Shigetoshi; Kuperberg, Gina R.; Tufts Univ., Medford, MA

The arcuate fasciculus (AF) in the human brain has asymmetric structural properties. However, the topographic organization of the asymmetric AF projections to the cortex and its relevance to cortical function remain unclear. Here we mapped the posterior projections of the human AF in the inferior parietal and lateral temporal cortices using surface-based structural connectivity analysis based on diffusion MRI and investigated their hemispheric differences. We then performed the cross-modal comparison with functional connectivity based on resting-state functional MRI (fMRI) and task-related cortical activation based on fMRI using a semantic classification task of single words. Structural connectivity analysis showed that themore » left AF connecting to Broca's area predominantly projected in the lateral temporal cortex extending from the posterior superior temporal gyrus to the mid part of the superior temporal sulcus and the middle temporal gyrus, whereas the right AF connecting to the right homolog of Broca's area predominantly projected to the inferior parietal cortex extending from the mid part of the supramarginal gyrus to the anterior part of the angular gyrus. The left-lateralized projection regions of the AF in the left temporal cortex had asymmetric functional connectivity with Broca's area, indicating structure-function concordance through the AF. During the language task, left-lateralized cortical activation was observed. Among them, the brain responses in the temporal cortex and Broca's area that were connected through the left-lateralized AF pathway were specifically correlated across subjects. These results suggest that the human left AF, which structurally and functionally connects the mid temporal cortex and Broca's area in asymmetrical fashion, coordinates the cortical activity in these remote cortices during a semantic decision task. As a result, the unique feature of the left AF is discussed in the context of the human capacity for language.« less

Asymmetric projections of the arcuate fasciculus to the temporal cortex underlie lateralized language function in the human brain

DOE PAGES

Takaya, Shigetoshi; Kuperberg, Gina R.; Tufts Univ., Medford, MA; ...

2015-09-15

The arcuate fasciculus (AF) in the human brain has asymmetric structural properties. However, the topographic organization of the asymmetric AF projections to the cortex and its relevance to cortical function remain unclear. Here we mapped the posterior projections of the human AF in the inferior parietal and lateral temporal cortices using surface-based structural connectivity analysis based on diffusion MRI and investigated their hemispheric differences. We then performed the cross-modal comparison with functional connectivity based on resting-state functional MRI (fMRI) and task-related cortical activation based on fMRI using a semantic classification task of single words. Structural connectivity analysis showed that themore » left AF connecting to Broca's area predominantly projected in the lateral temporal cortex extending from the posterior superior temporal gyrus to the mid part of the superior temporal sulcus and the middle temporal gyrus, whereas the right AF connecting to the right homolog of Broca's area predominantly projected to the inferior parietal cortex extending from the mid part of the supramarginal gyrus to the anterior part of the angular gyrus. The left-lateralized projection regions of the AF in the left temporal cortex had asymmetric functional connectivity with Broca's area, indicating structure-function concordance through the AF. During the language task, left-lateralized cortical activation was observed. Among them, the brain responses in the temporal cortex and Broca's area that were connected through the left-lateralized AF pathway were specifically correlated across subjects. These results suggest that the human left AF, which structurally and functionally connects the mid temporal cortex and Broca's area in asymmetrical fashion, coordinates the cortical activity in these remote cortices during a semantic decision task. As a result, the unique feature of the left AF is discussed in the context of the human capacity for language.« less

Pre-flight report on cultured human embryonic kidney cell handling and cell electrophoresis. Prepared prior to continuous-flow electrophoretic separation experiments aboard space shuttle flight STS-8

NASA Technical Reports Server (NTRS)

Todd, P. W.; Sarnoff, B. E.; Li, Z. K.

1985-01-01

Studies of the physical properties of continuous-flow zero-G electrophoretic separator (CFES) buffer, the electrokinetic properties of human erythrocytes in the CFES buffer, the electrokinetic properties of human embryonic kidney cells in the CFES buffer, and the viability and yield of human embryonc kidney cells subjected to flight handling procedures are discussed. In general, the procedure for cell handling and electrophoresis of HEK-8514 cells in 1st or 2nd passage on STS-8 is acceptable if executed properly. The CFES buffer has ionic strength that is barely compatible with cell viability and membrane stability, as seen in experiments with human erythrocytes and trypan-blue staining of human kidney cells. Cells suspended in 10% dialysed horse serum for 3 days in the cold appear to be more stable than freshly trypsinized cells. 10% horse serum appears to be superior to 5% horse serum for this purpose. The mean absolute raw mobility of HEK-8514 cells in CFES buffer at 6 degrees, conductivity 0.055 mmho/cm, is 1.1 to 1.4 um-cm/V-sec, with a range of nearly a whole mobility unit.

Columnar Segregation of Magnocellular and Parvocellular Streams in Human Extrastriate Cortex

PubMed Central

2017-01-01

Magnocellular versus parvocellular (M-P) streams are fundamental to the organization of macaque visual cortex. Segregated, paired M-P streams extend from retina through LGN into V1. The M stream extends further into area V5/MT, and parts of V2. However, elsewhere in visual cortex, it remains unclear whether M-P-derived information (1) becomes intermixed or (2) remains segregated in M-P-dominated columns and neurons. Here we tested whether M-P streams exist in extrastriate cortical columns, in 8 human subjects (4 female). We acquired high-resolution fMRI at high field (7T), testing for M- and P-influenced columns within each of four cortical areas (V2, V3, V3A, and V4), based on known functional distinctions in M-P streams in macaque: (1) color versus luminance, (2) binocular disparity, (3) luminance contrast sensitivity, (4) peak spatial frequency, and (5) color/spatial interactions. Additional measurements of resting state activity (eyes closed) tested for segregated functional connections between these columns. We found M- and P-like functions and connections within and between segregated cortical columns in V2, V3, and (in most experiments) area V4. Area V3A was dominated by the M stream, without significant influence from the P stream. These results suggest that M-P streams exist, and extend through, specific columns in early/middle stages of human extrastriate cortex. SIGNIFICANCE STATEMENT The magnocellular and parvocellular (M-P) streams are fundamental components of primate visual cortical organization. These streams segregate both anatomical and functional properties in parallel, from retina through primary visual cortex. However, in most higher-order cortical sites, it is unknown whether such M-P streams exist and/or what form those streams would take. Moreover, it is unknown whether M-P streams exist in human cortex. Here, fMRI evidence measured at high field (7T) and high resolution revealed segregated M-P streams in four areas of human extrastriate cortex. These results suggest that M-P information is processed in segregated parallel channels throughout much of human visual cortex; the M-P streams are more than a convenient sorting property in earlier stages of the visual system. PMID:28724749

Susceptibility of Primary Sensory Cortex to Spreading Depolarizations.

PubMed

Bogdanov, Volodymyr B; Middleton, Natalie A; Theriot, Jeremy J; Parker, Patrick D; Abdullah, Osama M; Ju, Y Sungtaek; Hartings, Jed A; Brennan, K C

2016-04-27

Spreading depolarizations (SDs) are recognized as actors in neurological disorders as diverse as migraine and traumatic brain injury (TBI). Migraine aura involves sensory percepts, suggesting that sensory cortices might be intrinsically susceptible to SDs. We used optical imaging, MRI, and field potential and potassium electrode recordings in mice and electrocorticographic recordings in humans to determine the susceptibility of different brain regions to SDs. Optical imaging experiments in mice under isoflurane anesthesia showed that both cortical spreading depression and terminal anoxic depolarization arose preferentially in the whisker barrel region of parietal sensory cortex. MRI recordings under isoflurane, ketamine/xylazine, ketamine/isoflurane, and urethane anesthesia demonstrated that the depolarizations did not propagate from a subcortical source. Potassium concentrations showed larger increases in sensory cortex, suggesting a mechanism of susceptibility. Sensory stimulation biased the timing but not the location of depolarization onset. In humans with TBI, there was a trend toward increased incidence of SDs in parietal/temporal sensory cortex compared with other regions. In conclusion, SDs are inducible preferentially in primary sensory cortex in mice and most likely in humans. This tropism can explain the predominant sensory phenomenology of migraine aura. It also demonstrates that sensory cortices are vulnerable in brain injury. Spreading depolarizations (SDs) are involved in neurologic disorders as diverse as migraine and traumatic brain injury. In migraine, the nature of aura symptoms suggests that sensory cortex may be preferentially susceptible. In brain injury, SDs occur at a vulnerable time, during which the issue of sensory stimulation is much debated. We show, in mouse and human, that sensory cortex is more susceptible to SDs. We find that sensory stimulation biases the timing but not the location of the depolarizations. Finally, we show a relative impairment of potassium clearance in sensory cortex, providing a potential mechanism for the susceptibility. Our data help to explain the sensory nature of the migraine aura and reveal that sensory cortices are vulnerable in brain injury. Copyright © 2016 the authors 0270-6474/16/364733-11$15.00/0.

Susceptibility of Primary Sensory Cortex to Spreading Depolarizations

PubMed Central

Bogdanov, Volodymyr B.; Middleton, Natalie A.; Theriot, Jeremy J.; Parker, Patrick D.; Abdullah, Osama M.; Ju, Y. Sungtaek; Hartings, Jed A.

2016-01-01

Spreading depolarizations (SDs) are recognized as actors in neurological disorders as diverse as migraine and traumatic brain injury (TBI). Migraine aura involves sensory percepts, suggesting that sensory cortices might be intrinsically susceptible to SDs. We used optical imaging, MRI, and field potential and potassium electrode recordings in mice and electrocorticographic recordings in humans to determine the susceptibility of different brain regions to SDs. Optical imaging experiments in mice under isoflurane anesthesia showed that both cortical spreading depression and terminal anoxic depolarization arose preferentially in the whisker barrel region of parietal sensory cortex. MRI recordings under isoflurane, ketamine/xylazine, ketamine/isoflurane, and urethane anesthesia demonstrated that the depolarizations did not propagate from a subcortical source. Potassium concentrations showed larger increases in sensory cortex, suggesting a mechanism of susceptibility. Sensory stimulation biased the timing but not the location of depolarization onset. In humans with TBI, there was a trend toward increased incidence of SDs in parietal/temporal sensory cortex compared with other regions. In conclusion, SDs are inducible preferentially in primary sensory cortex in mice and most likely in humans. This tropism can explain the predominant sensory phenomenology of migraine aura. It also demonstrates that sensory cortices are vulnerable in brain injury. SIGNIFICANCE STATEMENT Spreading depolarizations (SDs) are involved in neurologic disorders as diverse as migraine and traumatic brain injury. In migraine, the nature of aura symptoms suggests that sensory cortex may be preferentially susceptible. In brain injury, SDs occur at a vulnerable time, during which the issue of sensory stimulation is much debated. We show, in mouse and human, that sensory cortex is more susceptible to SDs. We find that sensory stimulation biases the timing but not the location of the depolarizations. Finally, we show a relative impairment of potassium clearance in sensory cortex, providing a potential mechanism for the susceptibility. Our data help to explain the sensory nature of the migraine aura and reveal that sensory cortices are vulnerable in brain injury. PMID:27122032

Online mentalising investigated with functional MRI.

PubMed

Kircher, Tilo; Blümel, Isabelle; Marjoram, Dominic; Lataster, Tineke; Krabbendam, Lydia; Weber, Jochen; van Os, Jim; Krach, Sören

2009-05-01

For successful interpersonal communication, inferring intentions, goals or desires of others is highly advantageous. Increasingly, humans also interact with computers or robots. In this study, we sought to determine to what degree an interactive task, which involves receiving feedback from social partners that can be used to infer intent, engaged the medial prefrontal cortex, a region previously associated with Theory of Mind processes among others. Participants were scanned using fMRI as they played an adapted version of the Prisoner's Dilemma Game with alleged human and computer partners who were outside the scanner. The medial frontal cortex was activated when both human and computer partner were played, while the direct contrast revealed significantly stronger signal change during the human-human interaction. The results suggest a link between activity in the medial prefrontal cortex and the partner played in a mentalising task. This signal change was also present for to the computers partner. Implying agency or a will to non-human actors might be an innate human resource that could lead to an evolutionary advantage.

A homozygous missense variant in VWA2, encoding an interactor of the Fraser-complex, in a patient with vesicoureteral reflux.

PubMed

van der Ven, Amelie T; Kobbe, Birgit; Kohl, Stefan; Shril, Shirlee; Pogoda, Hans-Martin; Imhof, Thomas; Ityel, Hadas; Vivante, Asaf; Chen, Jing; Hwang, Daw-Yang; Connaughton, Dervla M; Mann, Nina; Widmeier, Eugen; Taglienti, Mary; Schmidt, Johanna Magdalena; Nakayama, Makiko; Senguttuvan, Prabha; Kumar, Selvin; Tasic, Velibor; Kehinde, Elijah O; Mane, Shrikant M; Lifton, Richard P; Soliman, Neveen; Lu, Weining; Bauer, Stuart B; Hammerschmidt, Matthias; Wagener, Raimund; Hildebrandt, Friedhelm

2018-01-01

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause (40-50%) of chronic kidney disease (CKD) in children. About 40 monogenic causes of CAKUT have so far been discovered. To date less than 20% of CAKUT cases can be explained by mutations in these 40 genes. To identify additional monogenic causes of CAKUT, we performed whole exome sequencing (WES) and homozygosity mapping (HM) in a patient with CAKUT from Indian origin and consanguineous descent. We identified a homozygous missense mutation (c.1336C>T, p.Arg446Cys) in the gene Von Willebrand factor A domain containing 2 (VWA2). With immunohistochemistry studies on kidneys of newborn (P1) mice, we show that Vwa2 and Fraser extracellular matrix complex subunit 1 (Fras1) co-localize in the nephrogenic zone of the renal cortex. We identified a pronounced expression of Vwa2 in the basement membrane of the ureteric bud (UB) and derivatives of the metanephric mesenchyme (MM). By applying in vitro assays, we demonstrate that the Arg446Cys mutation decreases translocation of monomeric VWA2 protein and increases translocation of aggregated VWA2 protein into the extracellular space. This is potentially due to the additional, unpaired cysteine residue in the mutated protein that is used for intermolecular disulfide bond formation. VWA2 is a known, direct interactor of FRAS1 of the Fraser-Complex (FC). FC-encoding genes and interacting proteins have previously been implicated in the pathogenesis of syndromic and/or isolated CAKUT phenotypes in humans. VWA2 therefore constitutes a very strong candidate in the search for novel CAKUT-causing genes. Our results from in vitro experiments indicate a dose-dependent neomorphic effect of the Arg446Cys homozygous mutation in VWA2.

Acute and Chronic Kidney Injury in a Non-Human Primate Model of Partial-Body Irradiation with Bone Marrow Sparing.

PubMed

Cohen, Eric P; Hankey, Kim G; Bennett, Alexander W; Farese, Ann M; Parker, George A; MacVittie, Thomas J

2017-12-01

The development of medical countermeasures against acute and delayed multi-organ injury requires animal models predictive of the human response to radiation and its treatment. Late chronic injury is a well-known feature of radiation nephropathy, but acute kidney injury has not been reported in an appropriate animal model. We have established a single-fraction partial-body irradiation model with minimal marrow sparing in non-human primates. Subject-based medical management was used including parenteral fluids according to prospective morbidity criteria. We show herein that 10 or 11 Gy exposures caused both acute and chronic kidney injury. Acute and chronic kidney injury appear to be dose-independent between 10 and 11 Gy. Acute kidney injury was identified during the first 50 days postirradiation and appeared to resolve before the occurrence of chronic kidney injury, which was progressively more severe up to 180 days postirradiation, which was the end of the study. These findings show that mitigation of the acute radiation syndrome by medical management will unmask delayed late effects that occur months after partial-body irradiation. They further emphasize that both acute and chronic changes in kidney function must be taken into account in the use and timing of mitigators and medical management for acute radiation syndrome and delayed effects of acute radiation exposure (DEARE).

Frequency preference and attention effects across cortical depths in the human primary auditory cortex.

PubMed

De Martino, Federico; Moerel, Michelle; Ugurbil, Kamil; Goebel, Rainer; Yacoub, Essa; Formisano, Elia

2015-12-29

Columnar arrangements of neurons with similar preference have been suggested as the fundamental processing units of the cerebral cortex. Within these columnar arrangements, feed-forward information enters at middle cortical layers whereas feedback information arrives at superficial and deep layers. This interplay of feed-forward and feedback processing is at the core of perception and behavior. Here we provide in vivo evidence consistent with a columnar organization of the processing of sound frequency in the human auditory cortex. We measure submillimeter functional responses to sound frequency sweeps at high magnetic fields (7 tesla) and show that frequency preference is stable through cortical depth in primary auditory cortex. Furthermore, we demonstrate that-in this highly columnar cortex-task demands sharpen the frequency tuning in superficial cortical layers more than in middle or deep layers. These findings are pivotal to understanding mechanisms of neural information processing and flow during the active perception of sounds.

Regenerating the kidney using human pluripotent stem cells and renal progenitors.

PubMed

Becherucci, Francesca; Mazzinghi, Benedetta; Allinovi, Marco; Angelotti, Maria Lucia; Romagnani, Paola

2018-06-25

Introduction Chronic kidney disease is a major healthcare problem worldwide and its cost is becoming no longer affordable. Indeed, restoring damaged renal structures or building a new kidney represent an ambitious and ideal alternative to renal replacement therapy. Streams of research have explored the possible application of pluripotent SCs (embryonic SCs and induced pluripotent SCs) in different strategies aimed at regenerate functioning nephrons and at understanding the mechanisms of kidney regeneration. Areas covered In this review, we will focus on the main potential applications of human pluripotent SCs to kidney regeneration, including those leading to rebuilding new kidneys or part of them (organoids, scaffolds, biological microdevices) as well as those aimed at understanding the pathophysiological mechanisms of renal disease and regenerative processes (modeling of kidney disease, genome editing). Moreover, we will discuss the role of endogenous renal progenitors cells in order to understand and promote kidney regeneration, as an attractive alternative to pluripotent SCs. Expert opinion Opportunities and pitfalls of all these strategies will be underlined, finally leading to the conclusion that a deeper knowledge of the biology of pluripotent SCs is mandatory, in order to allow us to hypothesize their clinical application.

Formula Feeding Is Independently Associated With Acute Kidney Injury in Very Low Birth Weight Infants.

PubMed

Ginovart, Gemma; Gich, Ignasi; Verd, Sergio

2016-11-01

Successful strategies to prevent neonatal acute kidney injury are lacking. Nevertheless, it is well known that in breastfed babies the excretory needs of the kidney are low because the intake of most nutrients is just above the nutritional requirement. This study aimed to determine whether feeding type predicts acute kidney injury in the very low birth weight infant. One hundred and eighty-six infants were enrolled in this pre-post cohort study (114 infants were included in the only human milk-fed group and 72 in the formula-fed group). Routine biological markers of acute kidney injury were collected in both groups from birth to discharge. Compared with formula feeding, human milk feeding was associated with almost 80% lower odds of acute kidney injury (odds ratio [OR] = 0.2; 95% confidence interval [CI], 0.05-0.77). After confounding variables had been controlled for, formula feeding was independently associated with acute kidney injury in very low birth weight infants. The study showed that, at our institution, acute kidney injury in the neonatal period is frequently associated with the avoidable procedure of formula feeding. Further prospective multicenter studies are needed to determine the generality of this association.

Motivating forces of human actions. Neuroimaging reward and social interaction.

PubMed

Walter, Henrik; Abler, Birgit; Ciaramidaro, Angela; Erk, Susanne

2005-11-15

In neuroeconomics, reward and social interaction are central concepts to understand what motivates human behaviour. Both concepts are investigated in humans using neuroimaging methods. In this paper, we provide an overview about these results and discuss their relevance for economic behaviour. For reward it has been shown that a system exists in humans that is involved in predicting rewards and thus guides behaviour, involving a circuit including the striatum, the orbitofrontal cortex and the amygdala. Recent studies on social interaction revealed a mentalizing system representing the mental states of others. A central part of this system is the medial prefrontal cortex, in particular the anterior paracingulate cortex. The reward as well as the mentalizing system is engaged in economic decision-making. We will discuss implications of this study for neuromarketing as well as general implications of these results that may help to provide deeper insights into the motivating forces of human behaviour.

Role of pressure in angiotensin II-induced renal injury: chronic servo-control of renal perfusion pressure in rats.

PubMed

Mori, Takefumi; Cowley, Allen W

2004-04-01

Renal perfusion pressure was servo-controlled chronically in rats to quantify the relative contribution of elevated arterial pressure versus angiotensin II (Ang II) on the induction of renal injury in Ang II-induced hypertension. Sprague-Dawley rats fed a 4% salt diet were administered Ang II for 14 days (25 ng/kg per minute IV; saline only for sham rats), and the renal perfusion pressure to the left kidney was continuously servo-controlled to maintain a normal pressure in that kidney throughout the period of hypertension. An aortic occluder was implanted around the aorta between the two renal arteries and carotid and femoral arterial pressure were measured continuously throughout the experiment to determine uncontrolled and controlled renal perfusion pressure, respectively. Renal perfusion pressure of uncontrolled, controlled, and sham kidneys over the period of Ang II or saline infusion averaged 152.6+/-7.0, 117.4+/-3.5, and 110.7+/-2.2 mm Hg, respectively. The high-pressure uncontrolled kidneys exhibited tubular necrosis and interstitial fibrosis, especially prominent in the outer medullary region. Regional glomerular sclerosis and interlobular artery injury were also pronounced. Controlled kidneys were significantly protected from interlobular artery injury, juxtamedullary glomeruli injury, tubular necrosis, and interstitial fibrosis as determined by comparing the level of injury. Glomerular injury was not prevented in the outer cortex. Transforming growth factor (TGF)-beta and active NF-kappaB proteins determined by immunohistochemistry were colocalized in the uncontrolled kidney in regions of interstitial fibrosis. We conclude that the preferential juxtamedullary injury found in Ang II hypertension is largely induced by pressure and is probably mediated through the TGF-beta and NF-kappaB pathway.

Loganin attenuates diabetic nephropathy in C57BL/6J mice with diabetes induced by streptozotocin and fed with diets containing high level of advanced glycation end products.

PubMed

Liu, Kai; Xu, Huiqin; Lv, Gaohong; Liu, Bin; Lee, Maxwell Kim Kit; Lu, Chunhong; Lv, Xing; Wu, Yunhao

2015-02-15

Diabetic nephropathy is the most common cause of end-stage renal disease in patients with diabetes. Advanced glycation end-products (AGEs) play a prominent role in the development of diabetic nephropathy. We herein evaluated the effects of loganin on diabetic nephropathy in vivo. We established a diabetic nephropathy model in C57BL/6J mice with diabetes induced by streptozotocin and fed with diets containing high level of AGEs. Diabetic symptoms, renal functions, and pathohistology of pancreas and kidney were evaluated. AGE-RAGE pathway and oxidative stress parameters were determined. The model mice exhibited characteristic symptoms of diabetes including weight loss, polydipsia, polyphagia, polyuria, elevated blood glucose levels and low serum insulin levels during the experiments. However, loganin at doses of 0.02 and 0.1g/kg effectively improved these diabetic symptoms. Loganin reduced kidney/body weight ratio, 24h urine protein levels, and serum levels of urea nitrogen and creatinine in diabetic mice to different degrees compared to positive controls. Moreover, loganin improved the histology of pancreas and kidney, and alleviated the structural alterations in endothelial cells, mesangial cells and podocytes in renal cortex. Finally, we found that loganin reduced AGE levels in serum and kidney and downregulated mRNA and protein expression of receptors for AGEs in kidney in diabetic mice. Loganin also reduced the levels of malondialdehyde and increased the levels of superoxide dismutase in serum and kidney. Loganin improved diabetic nephropathy in vivo associated with inhibition of AGE pathways, and could be a promising remedy for diabetic nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.

Early activation of deleterious molecular pathways in the kidney in experimental heart failure with atrial remodeling.

PubMed

Ichiki, Tomoko; Huntley, Brenda K; Harty, Gail J; Sangaralingham, S Jeson; Burnett, John C

2017-05-01

Heart failure (HF) is a major health problem with worsening outcomes when renal impairment is present. Therapeutics for early phase HF may be effective for cardiorenal protection, however the detailed characteristics of the kidney in early-stage HF (ES-HF), and therefore treatment for potential renal protection, are poorly defined. We sought to determine the gene and protein expression profiles of specific maladaptive pathways of ES-HF in the kidney and heart. Experimental canine ES-HF, characterized by de-novo HF with atrial remodeling but not ventricular fibrosis, was induced by right ventricular pacing for 10 days. Kidney cortex (KC), medulla (KM), left ventricle (LV), and left atrial (LA) tissues from ES-HF versus normal canines ( n  = 4 of each) were analyzed using RT-PCR microarrays and protein assays to assess genes and proteins related to inflammation, renal injury, apoptosis, and fibrosis. ES-HF was characterized by increased circulating natriuretic peptides and components of the renin-angiotensin-aldosterone system and decreased sodium and water excretion with mild renal injury and up-regulation of CNP and renin genes in the kidney. Compared to normals, widespread genes, especially genes of the inflammatory pathways, were up-regulated in KC similar to increases seen in LA Protein expressions related to inflammatory cytokines were also augmented in the KC Gene and protein changes were less prominent in the LV and KM The ES-HF displayed mild renal injury with widespread gene changes and increased inflammatory cytokines. These changes may provide important clues into the pathophysiology of ES-HF and for therapeutic molecular targets in the kidney of ES-HF. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Intra-Abdominal Cooling System Limits Ischemia-Reperfusion Injury During Robot-Assisted Renal Transplantation.

PubMed

Meier, R P H; Piller, V; Hagen, M E; Joliat, C; Buchs, J-B; Nastasi, A; Ruttimann, R; Buchs, N C; Moll, S; Vallée, J-P; Lazeyras, F; Morel, P; Bühler, L

2018-01-01

Robot-assisted kidney transplantation is feasible; however, concerns have been raised about possible increases in warm ischemia times. We describe a novel intra-abdominal cooling system to continuously cool the kidney during the procedure. Porcine kidneys were procured by standard open technique. Groups were as follows: Robotic renal transplantation with (n = 11) and without (n = 6) continuous intra-abdominal cooling and conventional open technique with intermittent 4°C saline cooling (n = 6). Renal cortex temperature, magnetic resonance imaging, and histology were analyzed. Robotic renal transplantation required a longer anastomosis time, either with or without the cooling system, compared to the open approach (70.4 ± 17.7 min and 74.0 ± 21.5 min vs. 48.7 ± 11.2 min, p-values < 0.05). The temperature was lower in the robotic group with cooling system compared to the open approach group (6.5 ± 3.1°C vs. 22.5 ± 6.5°C; p = 0.001) or compared to the robotic group without the cooling system (28.7 ± 3.3°C; p < 0.001). Magnetic resonance imaging parenchymal heterogeneities and histologic ischemia-reperfusion lesions were more severe in the robotic group without cooling than in the cooled (open and robotic) groups. Robot-assisted kidney transplantation prolongs the warm ischemia time of the donor kidney. We developed a novel intra-abdominal cooling system that suppresses the noncontrolled rewarming of donor kidneys during the transplant procedure and prevents ischemia-reperfusion injuries. © 2017 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.

Non-neuronal expression of choline acetyltransferase in the rat kidney.

PubMed

Maeda, Seishi; Jun, Jin Gon; Kuwahara-Otani, Sachi; Tanaka, Koichi; Hayakawa, Tetsu; Seki, Makoto

2011-09-12

Acetylcholine (ACh) has been shown to increase ion and water excretion in the kidneys, resulting in hypotension. However, no evidence of renal parasympathetic innervation has been shown, and the source of ACh acting on nephrons is still unknown. The aim of the present study was to identify ACh-producing cells in the rat kidney, by examining the expression of cholinergic agents and localization of an ACh-synthesizing enzyme, choline acetyltransferase (ChAT), in the kidney. Adult mail Sprague-Dawley rats were used in this study. Expression of mRNA of cholinergic agents, ChAT, vesicular ACh transporter (VAChT), and high-affinity choline transporter (CHT-1), in the kidney was examined by RT-PCR. Localization of ChAT mRNA and protein was examined by in situ hybridization and tyramide-enhanced immunohistochemistry, respectively. RT-PCR showed the expression of ChAT, VAChT, and CHT-1. In situ hybridization demonstrated that ChAT mRNA is localized to the renal cortical collecting ducts (CCD). Immunohistochemistry showed that the ChAT-positive cells were principal cells, and that they were unevenly distributed in the tubules, and constituted approximately 15.2% of CCD in the cortex, and 3.6% and 1.5% in the outer and inner medulla, respectively. ChAT-positive immunoreactivity was localized to the apical side of principal cells, suggesting that ACh synthesis may occur in the apical compartment of these cells. These results suggest that the cholinergic effects in the nephron may be mediated at least in part by ACh originating from CCD principal cells and its expression may be locally regulated in the rat kidney. Copyright © 2011 Elsevier Inc. All rights reserved.

N-acetyl-cysteine increases cellular dysfunction in progressive chronic kidney damage after acute kidney injury by dampening endogenous antioxidant responses.

PubMed

Small, David M; Sanchez, Washington Y; Roy, Sandrine F; Morais, Christudas; Brooks, Heddwen L; Coombes, Jeff S; Johnson, David W; Gobe, Glenda C

2018-05-01

Oxidative stress and mitochondrial dysfunction exacerbate acute kidney injury (AKI), but their role in any associated progress to chronic kidney disease (CKD) remains unclear. Antioxidant therapies often benefit AKI, but their benefits in CKD are controversial since clinical and preclinical investigations often conflict. Here we examined the influence of the antioxidant N-acetyl-cysteine (NAC) on oxidative stress and mitochondrial function during AKI (20-min bilateral renal ischemia plus reperfusion/IR) and progression to chronic kidney pathologies in mice. NAC (5% in diet) was given to mice 7 days prior and up to 21 days post-IR (21d-IR). NAC treatment resulted in the following: prevented proximal tubular epithelial cell apoptosis at early IR (40-min postischemia), yet enhanced interstitial cell proliferation at 21d-IR; increased transforming growth factor-β1 expression independent of IR time; and significantly dampened nuclear factor-like 2-initiated cytoprotective signaling at early IR. In the long term, NAC enhanced cellular metabolic impairment demonstrated by increased peroxisome proliferator activator-γ serine-112 phosphorylation at 21d-IR. Intravital multiphoton microscopy revealed increased endogenous fluorescence of nicotinamide adenine dinucleotide (NADH) in cortical tubular epithelial cells during ischemia, and at 21d-IR that was not attenuated with NAC. Fluorescence lifetime imaging microscopy demonstrated persistent metabolic impairment by increased free/bound NADH in the cortex at 21d-IR that was enhanced by NAC. Increased mitochondrial dysfunction in remnant tubular cells was demonstrated at 21d-IR by tetramethylrhodamine methyl ester fluorimetry. In summary, NAC enhanced progression to CKD following AKI not only by dampening endogenous cellular antioxidant responses at time of injury but also by enhancing persistent kidney mitochondrial and metabolic dysfunction.

A Short-Term Biological Indicator for Long-Term Kidney Damage after Radionuclide Therapy in Mice

PubMed Central

Pellegrini, Giovanni; Siwowska, Klaudia; Haller, Stephanie; Antoine, Daniel J.; Schibli, Roger; Kipar, Anja; Müller, Cristina

2017-01-01

Folate receptor (FR)-targeted radionuclide therapy using folate radioconjugates is of interest due to the expression of the FR in a variety of tumor types. The high renal accumulation of radiofolates presents, however, a risk of radionephropathy. A potential option to address this challenge would be to use radioprotectants, such as amifostine. Methods for early detection of kidney damage that—in this case—cannot be predicted based on dose estimations, would facilitate the development of novel therapies. The aim of this study was, therefore, to assess potentially changing levels of plasma and urine biomarkers and to determine DNA damage at an early stage after radiofolate application. The identification of an early indicator for renal damage in mice would be useful since histological changes become apparent only several months after treatment. Mice were injected with different quantities of 177Lu-folate (10 MBq, 20 MBq and 30 MBq), resulting in mean absorbed kidney doses of ~23 Gy, ~46 Gy and ~69 Gy, respectively, followed by euthanasia two weeks (>85% of the mean renal radiation dose absorbed) or three months later. Whereas all investigated biomarkers remained unchanged, the number of γ-H2AX-positive nuclei in the renal cortex showed an evident dose-dependent increase as compared to control values two weeks after treatment. Comparison with the extent of kidney injury determined by histological changes five to eight months after administration of the same 177Lu-folate activities suggested that the quantitative assessment of double-strand breaks can be used as a biological indicator for long-term radiation effects in the kidneys. This method may, thus, enable faster assessment of radiopharmaceuticals and protective measures by preventing logistically challenging long-term investigations to detect kidney damage. PMID:28635637

Spatially Directed Proteomics of the Human Lens Outer Cortex Reveals an Intermediate Filament Switch Associated With the Remodeling Zone

PubMed Central

Wenke, Jamie L.; McDonald, W. Hayes; Schey, Kevin L.

2016-01-01

Purpose To quantify protein changes in the morphologically distinct remodeling zone (RZ) and adjacent regions of the human lens outer cortex using spatially directed quantitative proteomics. Methods Lightly fixed human lens sections were deparaffinized and membranes labeled with fluorescent wheat germ agglutinin (WGA-TRITC). Morphology directed laser capture microdissection (LCM) was used to isolate tissue from four distinct regions of human lens outer cortex: differentiating zone (DF), RZ, transition zone (TZ), and inner cortex (IC). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) of the plasma membrane fraction from three lenses (21-, 22-, and 27-year) revealed changes in major cytoskeletal proteins including vimentin, filensin, and phakinin. Peptides from proteins of interest were quantified using multiple reaction monitoring (MRM) mass spectrometry and isotopically-labeled internal peptide standards. Results Results revealed an intermediate filament switch from vimentin to beaded filament proteins filensin and phakinin that occurred at the RZ. Several other cytoskeletal proteins showed significant changes between regions, while most crystallins remained unchanged. Targeted proteomics provided accurate, absolute quantification of these proteins and confirmed vimentin, periplakin, and periaxin decrease from the DF to the IC, while filensin, phakinin, and brain acid soluble protein 1 (BASP1) increase significantly at the RZ. Conclusions Mass spectrometry-compatible fixation and morphology directed laser capture enabled proteomic analysis of narrow regions in the human lens outer cortex. Results reveal dramatic cytoskeletal protein changes associated with the RZ, suggesting that one role of these proteins is in membrane deformation and/or the establishment of ball and socket joints in the human RZ. PMID:27537260

The Role of the Human Extrastriate Visual Cortex in Mirror Symmetry Discrimination: A TMS-Adaptation Study

ERIC Educational Resources Information Center

Cattaneo, Zaira; Mattavelli, Giulia; Papagno, Costanza; Herbert, Andrew; Silvanto, Juha

2011-01-01

The human visual system is able to efficiently extract symmetry information from the visual environment. Prior neuroimaging evidence has revealed symmetry-preferring neuronal representations in the dorsolateral extrastriate visual cortex; the objective of the present study was to investigate the necessity of these representations in symmetry…

Pharmacological characterization of CCKB receptors in human brain: no evidence for receptor heterogeneity.

PubMed

Kinze, S; Schöneberg, T; Meyer, R; Martin, H; Kaufmann, R

1996-10-11

In this paper, cholecystokinin (CCK) B-type binding sites were characterized with receptor binding studies in different human brain regions (various parts of cerebral cortex, basal ganglia, hippocampus, thalamus, cerebellar cortex) collected from 22 human postmortem brains. With the exception of the thalamus, where no specific CCK binding sites were found, a pharmacological characterization demonstrated a single class of high affinity CCK sites in all brain areas investigated. Receptor densities ranged from 0.5 fmol/mg protein (hippocampus) to 8.4 fmol/mg protein (nucleus caudatus). These CCK binding sites displayed a typical CCKA binding profile as shown in competition studies by using different CCK-related compounds and non peptide CCK antagonists discriminating between CCKA and CCKB sites. The rank order of agonist or antagonist potency in inhibiting specific sulphated [propionyl-3H]cholecystokinin octapeptide binding was similar and highly correlated for the brain regions investigated as demonstrated by a computer-assisted analysis. Therefore it is concluded that CCKB binding sites in human cerebral cortex, basal ganglia, cerebellar cortex share identical ligand binding characteristics.

Independent effects of motivation and spatial attention in the human visual cortex.

PubMed

Bayer, Mareike; Rossi, Valentina; Vanlessen, Naomi; Grass, Annika; Schacht, Annekathrin; Pourtois, Gilles

2017-01-01

Motivation and attention constitute major determinants of human perception and action. Nonetheless, it remains a matter of debate whether motivation effects on the visual cortex depend on the spatial attention system, or rely on independent pathways. This study investigated the impact of motivation and spatial attention on the activity of the human primary and extrastriate visual cortex by employing a factorial manipulation of the two factors in a cued pattern discrimination task. During stimulus presentation, we recorded event-related potentials and pupillary responses. Motivational relevance increased the amplitudes of the C1 component at ∼70 ms after stimulus onset. This modulation occurred independently of spatial attention effects, which were evident at the P1 level. Furthermore, motivation and spatial attention had independent effects on preparatory activation as measured by the contingent negative variation; and pupil data showed increased activation in response to incentive targets. Taken together, these findings suggest independent pathways for the influence of motivation and spatial attention on the activity of the human visual cortex. © The Author (2016). Published by Oxford University Press.

Human Pluripotent Stem-Cell-Derived Cortical Neurons Integrate Functionally into the Lesioned Adult Murine Visual Cortex in an Area-Specific Way.

PubMed

Espuny-Camacho, Ira; Michelsen, Kimmo A; Linaro, Daniele; Bilheu, Angéline; Acosta-Verdugo, Sandra; Herpoel, Adèle; Giugliano, Michele; Gaillard, Afsaneh; Vanderhaeghen, Pierre

2018-05-29

The transplantation of pluripotent stem-cell-derived neurons constitutes a promising avenue for the treatment of several brain diseases. However, their potential for the repair of the cerebral cortex remains unclear, given its complexity and neuronal diversity. Here, we show that human visual cortical cells differentiated from embryonic stem cells can be transplanted and can integrate successfully into the lesioned mouse adult visual cortex. The transplanted human neurons expressed the appropriate repertoire of markers of six cortical layers, projected axons to specific visual cortical targets, and were synaptically active within the adult brain. Moreover, transplant maturation and integration were much less efficient following transplantation into the lesioned motor cortex, as previously observed for transplanted mouse cortical neurons. These data constitute an important milestone for the potential use of human PSC-derived cortical cells for the reassembly of cortical circuits and emphasize the importance of cortical areal identity for successful transplantation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Mucopolysaccharidosis-like phenotype in feline Sandhoff disease and partial correction after AAV gene therapy.

PubMed

Gray-Edwards, Heather L; Brunson, Brandon L; Holland, Merrilee; Hespel, Adrien-Maxence; Bradbury, Allison M; McCurdy, Victoria J; Beadlescomb, Patricia M; Randle, Ashley N; Salibi, Nouha; Denney, Thomas S; Beyers, Ronald J; Johnson, Aime K; Voyles, Meredith L; Montgomery, Ronald D; Wilson, Diane U; Hudson, Judith A; Cox, Nancy R; Baker, Henry J; Sena-Esteves, Miguel; Martin, Douglas R

2015-01-01

Sandhoff disease (SD) is a fatal neurodegenerative disease caused by a mutation in the enzyme β-N-acetylhexosaminidase. Children with infantile onset SD develop seizures, loss of motor tone and swallowing problems, eventually reaching a vegetative state with death typically by 4years of age. Other symptoms include vertebral gibbus and cardiac abnormalities strikingly similar to those of the mucopolysaccharidoses. Isolated fibroblasts from SD patients have impaired catabolism of glycosaminoglycans (GAGs). To evaluate mucopolysaccharidosis-like features of the feline SD model, we utilized radiography, MRI, echocardiography, histopathology and GAG quantification of both central nervous system and peripheral tissues/fluids. The feline SD model exhibits cardiac valvular and structural abnormalities, skeletal changes and spinal cord compression that are consistent with accumulation of GAGs, but are much less prominent than the severe neurologic disease that defines the humane endpoint (4.5±0.5months). Sixteen weeks after intracranial AAV gene therapy, GAG storage was cleared in the SD cat cerebral cortex and liver, but not in the heart, lung, skeletal muscle, kidney, spleen, pancreas, small intestine, skin, or urine. GAG storage worsens with time and therefore may become a significant source of pathology in humans whose lives are substantially lengthened by gene therapy or other novel treatments for the primary, neurologic disease. Published by Elsevier Inc.

Morphology of human embryonic kidney cells in culture after space flight

NASA Technical Reports Server (NTRS)

Todd, P.; Kunze, M. E.; Williams, K.; Morrison, D. R.; Lewis, M. L.; Barlow, G. H.

1985-01-01

The ability of human embyronic kidney cells to differentiate into small epithelioid, large epithelioid, domed, and fenestrated morphological cell types following space flight is examined. Kidney cells exposed to 1 day at 1 g, then 1 day in orbit, and a 12 minute passage through the electrophoretic separator are compared with control cultures. The data reveal that 70 percent of small epithelioid, 16 percent of large epithelioid, 9 percent of dome-forming, and 5 percent of fenestrated cells formed in the space exposed cells; the distributions correlate well with control data. The formation of domed cells from cells cultured from low electrophoretic mobility fractions and small epithelioid cells from high mobility fractions is unaffected by space flight conditions. It is concluded that storage under microgravity conditions does not influence the morphological differentiation of human embryonic kidney cells in low-passage culture.

Kidney-on-a-Chip: a New Technology for Predicting Drug Efficacy, Interactions, and Drug-induced Nephrotoxicity.

PubMed

Lee, Jeonghwan; Kim, Sejoong

2018-03-08

The kidneys play a pivotal role in most drug-removal processes and are important when evaluating drug safety. Kidney dysfunction resulting from various drugs is an important issue in clinical practice and during the drug development process. Traditional in vivo animal experiments are limited with respect to evaluating drug efficacy and nephrotoxicity due to discrepancies in drug pharmacokinetics and pharmacodynamics between humans and animals, and static cell culture experiments cannot fully reflect the actual microphysiological environment in humans. A kidney-on-a-chip is a microfluidic device that allows the culture of living renal cells in 3-dimensional channels and mimics the human microphysiological environment, thus simulating the actual drug filtering, absorption, and secretion process.. In this review, we discuss recent developments in microfluidic culturing technique and describe current and future kidney-on-a-chip applications. We focus on pharmacological interactions and drug-induced nephrotoxicity, and additionally discuss the development of multi-organ chips and their possible applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Relationship between mercury in kidney, blood, and urine in environmentally exposed individuals, and implications for biomonitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akerstrom, Magnus, E-mail: magnus.akerstrom@amm.gu

Background: Individuals without occupational exposure are exposed to mercury (Hg) from diet and dental amalgam. The kidney is a critical organ, but there is limited information regarding the relationship between Hg in kidney (K-Hg), urine (U-Hg), blood (B-Hg), and plasma (P-Hg). Objectives: The aim was to determine the relationship between K-Hg, U-Hg, B-Hg, and P-Hg among environmentally exposed individuals, estimate the biological half-time of K-Hg, and provide information useful for biomonitoring of Hg. Methods: Kidney cortex biopsies and urine and blood samples were collected from 109 living kidney donors. Total Hg concentrations were determined and the relationships between K-Hg, U-Hg,more » P-Hg, and B-Hg were investigated in regression models. The half-time of K-Hg was estimated from the elimination constant. Results: There were strong associations between K-Hg and all measures of U-Hg and P-Hg (r{sub p} = 0.65–0.84, p < 0.001), while the association with B-Hg was weaker (r{sub p} = 0.29, p = 0.002). Mean ratios between K-Hg (in μg/g) and U-Hg/24h (in μg) and B-Hg (in μg/L) were 0.22 and 0.19 respectively. Estimates of the biological half-time varied between 30 and 92 days, with significantly slower elimination in women. Adjusting overnight urine samples for dilution using urinary creatinine resulted in less bias in relation to K-Hg or U-Hg/24h, compared with other adjustment techniques. Conclusions: The relationship between K-Hg and U-Hg is approximately linear. K-Hg can be estimated using U-Hg and gender. Women have longer half-time of Hg in kidney compared to men. Adjusting overnight urine samples for creatinine concentration resulted in less bias. - Highlights: • The first study of the relation between Hg in kidney, blood and urine at low U-Hg • Simultaneous samples were collected from healthy kidney donors. • There was a linear relationship between mercury in kidney and urine. • Kidney Hg can be estimated using U-Hg and gender. • Women have longer half-time of Hg in kidney compared to men.« less

Ginger extract diminishes chronic fructose consumption-induced kidney injury through suppression of renal overexpression of proinflammatory cytokines in rats.

PubMed

Yang, Ming; Liu, Changjin; Jiang, Jian; Zuo, Guowei; Lin, Xuemei; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

2014-05-27

The metabolic syndrome is associated with an increased risk of development and progression of chronic kidney disease. Renal inflammation is well known to play an important role in the initiation and progression of tubulointerstitial injury of the kidneys. Ginger, one of the most commonly used spices and medicinal plants, has been demonstrated to improve diet-induced metabolic abnormalities. However, the efficacy of ginger on the metabolic syndrome-associated kidney injury remains unknown. This study aimed to investigate the impact of ginger on fructose consumption-induced adverse effects in the kidneys. The fructose control rats were treated with 10% fructose in drinking water over 5 weeks. The fructose consumption in ginger-treated rats was adjusted to match that of fructose control group. The ethanolic extract of ginger was co-administered (once daily by oral gavage). The indexes of lipid and glucose homeostasis were determined enzymatically, by ELISA and/or histologically. Gene expression was analyzed by Real-Time PCR. In addition to improve hyperinsulinemia and hypertriglyceridemia, supplement with ginger extract (50 mg/kg) attenuated liquid fructose-induced kidney injury as characterized by focal cast formation, slough and dilation of tubular epithelial cells in the cortex of the kidneys in rats. Furthermore, ginger also diminished excessive renal interstitial collagen deposit. By Real-Time PCR, renal gene expression profiles revealed that ginger suppressed fructose-stimulated monocyte chemoattractant protein-1 and its receptor chemokine (C-C motif) receptor-2. In accord, overexpression of two important macrophage accumulation markers CD68 and F4/80 was downregulated. Moreover, overexpressed tumor necrosis factor-alpha, interleukin-6, transforming growth factor-beta1 and plasminogen activator inhibitor (PAI)-1 were downregulated. Ginger treatment also restored the downregulated ratio of urokinase-type plasminogen activator to PAI-1. The present results suggest that ginger supplement diminishes fructose-induced kidney injury through suppression of renal overexpression of macrophage-associated proinflammatory cytokines in rats. Our findings provide evidence supporting the protective effect of ginger on the metabolic syndrome-associated kidney injury.

Ginger extract diminishes chronic fructose consumption-induced kidney injury through suppression of renal overexpression of proinflammatory cytokines in rats

PubMed Central

2014-01-01

Background The metabolic syndrome is associated with an increased risk of development and progression of chronic kidney disease. Renal inflammation is well known to play an important role in the initiation and progression of tubulointerstitial injury of the kidneys. Ginger, one of the most commonly used spices and medicinal plants, has been demonstrated to improve diet-induced metabolic abnormalities. However, the efficacy of ginger on the metabolic syndrome-associated kidney injury remains unknown. This study aimed to investigate the impact of ginger on fructose consumption-induced adverse effects in the kidneys. Methods The fructose control rats were treated with 10% fructose in drinking water over 5 weeks. The fructose consumption in ginger-treated rats was adjusted to match that of fructose control group. The ethanolic extract of ginger was co-administered (once daily by oral gavage). The indexes of lipid and glucose homeostasis were determined enzymatically, by ELISA and/or histologically. Gene expression was analyzed by Real-Time PCR. Results In addition to improve hyperinsulinemia and hypertriglyceridemia, supplement with ginger extract (50 mg/kg) attenuated liquid fructose-induced kidney injury as characterized by focal cast formation, slough and dilation of tubular epithelial cells in the cortex of the kidneys in rats. Furthermore, ginger also diminished excessive renal interstitial collagen deposit. By Real-Time PCR, renal gene expression profiles revealed that ginger suppressed fructose-stimulated monocyte chemoattractant protein-1 and its receptor chemokine (C-C motif) receptor-2. In accord, overexpression of two important macrophage accumulation markers CD68 and F4/80 was downregulated. Moreover, overexpressed tumor necrosis factor-alpha, interleukin-6, transforming growth factor-beta1 and plasminogen activator inhibitor (PAI)-1 were downregulated. Ginger treatment also restored the downregulated ratio of urokinase-type plasminogen activator to PAI-1. Conclusions The present results suggest that ginger supplement diminishes fructose-induced kidney injury through suppression of renal overexpression of macrophage-associated proinflammatory cytokines in rats. Our findings provide evidence supporting the protective effect of ginger on the metabolic syndrome-associated kidney injury. PMID:24885946

The default mode network in chimpanzees (Pan troglodytes) is similar to that of humans.

PubMed

Barks, Sarah K; Parr, Lisa A; Rilling, James K

2015-02-01

The human default mode network (DMN), comprising medial prefrontal cortex, precuneus, posterior cingulate cortex, lateral parietal cortex, and medial temporal cortex, is highly metabolically active at rest but deactivates during most focused cognitive tasks. The DMN and social cognitive networks overlap significantly in humans. We previously demonstrated that chimpanzees (Pan troglodytes) show highest resting metabolic brain activity in the cortical midline areas of the human DMN. Human DMN is defined by task-induced deactivations, not absolute resting metabolic levels; ergo, resting activity is insufficient to define a DMN in chimpanzees. Here, we assessed the chimpanzee DMN's deactivations relative to rest during cognitive tasks and the effect of social content on these areas' activity. Chimpanzees performed a match-to-sample task with conspecific behavioral stimuli of varying sociality. Using [(18)F]-FDG PET, brain activity during these tasks was compared with activity during a nonsocial task and at rest. Cortical midline areas in chimpanzees deactivated in these tasks relative to rest, suggesting a chimpanzee DMN anatomically and functionally similar to humans. Furthermore, when chimpanzees make social discriminations, these same areas (particularly precuneus) are highly active relative to nonsocial tasks, suggesting that, as in humans, the chimpanzee DMN may play a role in social cognition. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Characterization of the blood-oxygen level-dependent (BOLD) response in cat auditory cortex using high-field fMRI.

PubMed

Brown, Trecia A; Joanisse, Marc F; Gati, Joseph S; Hughes, Sarah M; Nixon, Pam L; Menon, Ravi S; Lomber, Stephen G

2013-01-01

Much of what is known about the cortical organization for audition in humans draws from studies of auditory cortex in the cat. However, these data build largely on electrophysiological recordings that are both highly invasive and provide less evidence concerning macroscopic patterns of brain activation. Optical imaging, using intrinsic signals or dyes, allows visualization of surface-based activity but is also quite invasive. Functional magnetic resonance imaging (fMRI) overcomes these limitations by providing a large-scale perspective of distributed activity across the brain in a non-invasive manner. The present study used fMRI to characterize stimulus-evoked activity in auditory cortex of an anesthetized (ketamine/isoflurane) cat, focusing specifically on the blood-oxygen-level-dependent (BOLD) signal time course. Functional images were acquired for adult cats in a 7 T MRI scanner. To determine the BOLD signal time course, we presented 1s broadband noise bursts between widely spaced scan acquisitions at randomized delays (1-12 s in 1s increments) prior to each scan. Baseline trials in which no stimulus was presented were also acquired. Our results indicate that the BOLD response peaks at about 3.5s in primary auditory cortex (AI) and at about 4.5 s in non-primary areas (AII, PAF) of cat auditory cortex. The observed peak latency is within the range reported for humans and non-human primates (3-4 s). The time course of hemodynamic activity in cat auditory cortex also occurs on a comparatively shorter scale than in cat visual cortex. The results of this study will provide a foundation for future auditory fMRI studies in the cat to incorporate these hemodynamic response properties into appropriate analyses of cat auditory cortex. Copyright © 2012 Elsevier Inc. All rights reserved.

Development of rat female genital cortex and control of female puberty by sexual touch

PubMed Central

Lenschow, Constanze; Sigl-Glöckner, Johanna

2017-01-01

Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory) male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch. PMID:28934203

Development of rat female genital cortex and control of female puberty by sexual touch.

PubMed

Lenschow, Constanze; Sigl-Glöckner, Johanna; Brecht, Michael

2017-09-01

Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory) male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

Dietary cancer risk from conditional cancerogens (tumor promoters) in produce of livestock fed on species of spurge (Euphorbiaceae). IV. Toxicologic and pathophysiologic observations in lactating goats and their suckling kids fed on the irritant herbs Euphorbia nubica and Euphorbia helioscopia: an etiologic model for investigations on the putative risk of cancer by consumption of food p.

PubMed

Nawito, M; Ahmed, Y F; Shalaby, S I; Nada, A; Zayed, S M; Hecker, E

2001-01-01

The feeding of lactating goats on usual green fodder, contaminated with Euphorbia helioscopia or E. nubica, results in poisoning of the dams as well as their suckling kids. General signs of toxicity were emaciation, depression, shedding of body hair, arching of back, and possible death. Post-mortem changes of dams and dead suckling kids included congestion and hemorrhage in cardiac muscle, lung, liver, and kidneys. Blood analyses of goats exposed to these contaminants showed an increased level of serum alanine amino transferase compared to control samples, indicating cellular destruction in the liver. The latter was confirmed by histopathological changes in the organ which include severe congestion, necrosis, and degenerative changes. The goats also suffered from deterioration of renal function as indicated by increased blood urea nitrogen and creatinine levels. In histopathologic inspections of kidney, severe congestion, hemorrhage in the cortex and medulla, as well as necrosis of epithelial cells of kidney tubules were noticed. Considerable degenerative changes were also observed in heart and lung. The pathophysiological appearances indicate that by feeding on the Euphorbia species mentioned above, the goats are poisoned in a way similar to the case of E. peplus reported previously. Such intoxication most likely is due to irritant and hyperplasiogenic diterpene ester (DTE) toxins, usually present in the aerial parts of Euphorbia species and well known as tumor promoters in mouse skin. After ingestion of the toxic plant parts by the goats, the DTE toxins might be metabolized and thereby partially detoxified. Yet, at least in part, they may show up in the milk of the goats, as indicated by severe poisoning of their suckling kids. As discussed previously in lactating goats fed on fodder contaminated with E. peplus, tumor promoters of the DTE type may enter the human food chain via this source of milk. Such milk may be considered a valuable etiologic model for the investigation of economic, ecologic, and public health problems raised by human diet polluted with tumor promoters, i.e., conditional (non-genotoxic) cancerogens.

Indoxyl Sulfate Induces Apoptosis and Hypertrophy in Human Kidney Proximal Tubular Cells.

PubMed

Ellis, Robert J; Small, David M; Ng, Keng Lim; Vesey, David A; Vitetta, Luis; Francis, Ross S; Gobe, Glenda C; Morais, Christudas

2018-06-01

Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with declining kidney function. Although generally thought of as a consequence of declining kidney function, emerging evidence demonstrates direct cytotoxic role of IS on endothelial cells and cardiomyocytes, largely through the expression of pro-inflammatory and pro-fibrotic factors. The direct toxicity of IS on human kidney proximal tubular epithelial cells (PTECs) remains a matter of debate. The current study explored the effect of IS on primary cultures of human PTECs and HK-2, an immortalized human PTEC line. Pathologically relevant concentrations of IS induced apoptosis and increased the expression of the proapoptotic molecule Bax in both cell types. IS impaired mitochondrial metabolic activity and induced cellular hypertrophy. Furthermore, statistically significant upregulation of pro-fibrotic (transforming growth factor-β, fibronectin) and pro-inflammatory molecules (interleukin-6, interleukin-8, and tumor necrosis factor-α) in response to IS was observed. Albumin had no influence on the toxicity of IS. The results of this study suggest that IS directly induced a pro-inflammatory and pro-fibrotic phenotype in proximal tubular cells. In light of the associated apoptosis, hypertrophy, and metabolic dysfunction, this study demonstrates that IS may play a role in the progression of chronic kidney disease.

Human kidney anion exchanger 1 interacts with kinesin family member 3B (KIF3B)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duangtum, Natapol; Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700; Junking, Mutita

Highlights: {yields} Impaired trafficking of kAE1 causes distal renal tubular acidosis (dRTA). {yields} The interaction between kAE1 and kinesin family member 3B (KIF3B) is reported. {yields} The co-localization between kAE and KIF3B was detected in human kidney tissues. {yields} A marked reduction of kAE1 on the cell membrane was observed when KIF3B was knockdown. {yields} KFI3B plays an important role in trafficking of kAE1 to the plasma membrane. -- Abstract: Impaired trafficking of human kidney anion exchanger 1 (kAE1) to the basolateral membrane of {alpha}-intercalated cells of the kidney collecting duct leads to the defect of the Cl{sup -}/HCO{sub 3}{supmore » -} exchange and the failure of proton (H{sup +}) secretion at the apical membrane of these cells, causing distal renal tubular acidosis (dRTA). In the sorting process, kAE1 interacts with AP-1 mu1A, a subunit of AP-1A adaptor complex. However, it is not known whether kAE1 interacts with motor proteins in its trafficking process to the plasma membrane or not. We report here that kAE1 interacts with kinesin family member 3B (KIF3B) in kidney cells and a dileucine motif at the carboxyl terminus of kAE1 contributes to this interaction. We have also demonstrated that kAE1 co-localizes with KIF3B in human kidney tissues and the suppression of endogenous KIF3B in HEK293T cells by small interfering RNA (siRNA) decreases membrane localization of kAE1 but increases its intracellular accumulation. All results suggest that KIF3B is involved in the trafficking of kAE1 to the plasma membrane of human kidney {alpha}-intercalated cells.« less

Mapping of Carboxypeptidase M in Normal Human Kidney and Renal Cell Carcinoma

PubMed Central

Denis, Catherine J.; Van Acker, Nathalie; De Schepper, Stefanie; De Bie, Martine; Andries, Luc; Fransen, Erik; Hendriks, Dirk; Kockx, Mark M.

2013-01-01

Although the kidney generally has been regarded as an excellent source of carboxypeptidase M (CPM), little is known about its renal-specific expression level and distribution. This study provides a detailed localization of CPM in healthy and diseased human kidneys. The results indicate a broad distribution of CPM along the renal tubular structures in the healthy kidney. CPM was identified at the parietal epithelium beneath the Bowman’s basement membrane and in glomerular mesangial cells. Capillaries, podocytes, and most interstitial cells were CPM negative. Tumor cells of renal cell carcinoma subtypes lose CPM expression upon dedifferentiation. Tissue microarray analysis demonstrated a correlation between low CPM expression and tumor cell type. CPM staining was intense on phagocytotic tumor-associated macrophages. Immunoreactive CPM was also detected in the tumor-associated vasculature. The absence of CPM in normal renal blood vessels points toward a role for CPM in angiogenesis. Coexistence of CPM and the epidermal growth factor receptor (EGFR) was detected in papillary renal cell carcinoma. However, the different subcellular localization of CPM and EGFR argues against an interaction between these h proteins. The description of the distribution of CPM in human kidney forms the foundation for further study of the (patho)physiological activities of CPM in the kidney. PMID:23172796

Predicted consequences of diabetes and SGLT inhibition on transport and oxygen consumption along a rat nephron

PubMed Central

Vallon, Volker; Edwards, Aurélie

2016-01-01

Diabetes increases the reabsorption of Na+ (TNa) and glucose via the sodium-glucose cotransporter SGLT2 in the early proximal tubule (S1-S2 segments) of the renal cortex. SGLT2 inhibitors enhance glucose excretion and lower hyperglycemia in diabetes. We aimed to investigate how diabetes and SGLT2 inhibition affect TNa and sodium transport-dependent oxygen consumption QO2active along the whole nephron. To do so, we developed a mathematical model of water and solute transport from the Bowman space to the papillary tip of a superficial nephron of the rat kidney. Model simulations indicate that, in the nondiabetic kidney, acute and chronic SGLT2 inhibition enhances active TNa in all nephron segments, thereby raising QO2active by 5–12% in the cortex and medulla. Diabetes increases overall TNa and QO2active by ∼50 and 100%, mainly because it enhances glomerular filtration rate (GFR) and transport load. In diabetes, acute and chronic SGLT2 inhibition lowers QO2active in the cortex by ∼30%, due to GFR reduction that lowers proximal tubule active TNa, but raises QO2active in the medulla by ∼7%. In the medulla specifically, chronic SGLT2 inhibition is predicted to increase QO2active by 26% in late proximal tubules (S3 segments), by 2% in medullary thick ascending limbs (mTAL), and by 9 and 21% in outer and inner medullary collecting ducts (OMCD and IMCD), respectively. Additional blockade of SGLT1 in S3 segments enhances glucose excretion, reduces QO2active by 33% in S3 segments, and raises QO2active by <1% in mTAL, OMCD, and IMCD. In summary, the model predicts that SGLT2 blockade in diabetes lowers cortical QO2active and raises medullary QO2active, particularly in S3 segments. PMID:26764207

Characterization of human kidney stones using micro-PIXE and RBS: a comparative study between two different populations.

PubMed

Pineda-Vargas, C A; Eisa, M E M; Rodgers, A L

2009-03-01

The micro-PIXE and RBS techniques are used to investigate the matrix as well as the trace elemental composition of calcium-rich human tissues on a microscopic scale. This paper deals with the spatial distribution of trace metals in hard human tissues such as kidney stone concretions, undertaken at the nuclear microprobe (NMP) facility. Relevant information about ion beam techniques used for material characterization will be discussed. Mapping correlation between different trace metals to extract information related to micro-regions composition will be illustrated with an application using proton energies of 1.5 and 3.0 MeV and applied to a comparative study for human kidney stone concretions nucleation region analysis from two different population groups (Sudan and South Africa).

Role of Acetyl Salicylic Acid in Controlling the DOCA-Salt Induced Hypertension in Rats by Stimulating the Synthesis of r-Cortexin in the Kidney.

PubMed

Maji, Uttam Kumar; Jana, Pradipta; Chatterjee, Mitali; Karmakar, Sanmay; Saha, Arup; Ghosh, Tamal Kanti

2018-03-01

Hypertension is a metabolic disease which is caused by vasoconstriction and that results into elevated blood pressure. A chronic hypertensive condition affects and even damages to various systems in the body. Presence of renal cortexin (r-cortexin), an antihypertensive protein, which is released from the kidney cortex controls the blood pressure. The effect of r-cortexin was mediated through nitric oxide (NO), a universal vasodilating agent. In our study, acetyl salicylic acid (aspirin), a well-known activator of the endothelial nitric oxide synthase (eNOS) induced r-cortexin synthesis. The hypertensive rat model was prepared by injecting deoxy corticosterone acetate (DOCA). Synthesis of r-cortexin was measured by the anti-r-cortexin antibody which was raised in adult white Wister albino rat model. NO level was determined by using methemoglobin method and later confirmed by chemiluminescence method. Change in blood pressure was determined indirectly by using NIBP monitoring system. Aspirin increased the r-cortexin expression from 64.36 ± 12.6 nM to 216.7 ± 21.31 nM in DOCA induced hypertensive rats. The mechanism was proved with the findings of increased level of NO from 0.4 to 1.9 µM. The DOCA induced blood pressure was also decreased from 139.39 ± 7.36 mm of Hg to 116.57 ± 6.89 mm of Hg in case of systolic blood pressure and in case of diastolic pressure from 110.41 ± 7 mm of Hg to 86.4 ± 2.76 mm of Hg that are quite approximate. So, from this study it has been found that aspirin induces the r-cortexin synthesis in kidney cortex through the activation of eNOS in DOCA induced hypertensive rats.

Parvalbumin increases in the caudate putamen of rats with vitamin D hypervitaminosis.

PubMed Central

de Viragh, P A; Haglid, K G; Celio, M R

1989-01-01

The influence of chronic vitamin D3 application on the concentration of the four calcium-binding proteins parvalbumin, the 28-kDa calbindin-D, calmodulin, and S-100 was studied in various brain regions and in the kidney. Young rats were administered daily 20,000 international units of vitamin D3 per kg (body weight) over a period of 4 months. This chronic treatment resulted in a clinically mild hypervitaminosis that did not affect the content of calmodulin, the 28-kDa calbindin-D, and S-100. Also the concentration of parvalbumin in the cerebral cortex, hippocampus, and kidney remained unchanged. On the other hand, parvalbumin was increased about 50% in the caudate putamen of hypervitaminotic animals as compared to controls. Our results indicate that the metabolism of parvalbumin in the caudate putamen can be influenced by variations of the blood level of this steroid hormone. PMID:2542952

Investigation of the cortical activation by touching fabric actively using fingers.

PubMed

Wang, Q; Yu, W; He, N; Chen, K

2015-11-01

Human subjects can tactually estimate the perception of touching fabric. Although many psychophysical and neurophysiological experiments have elucidated the peripheral neural mechanisms that underlie fabric hand estimation, the associated cortical mechanisms are not well understood. To identify the brain regions responsible for the tactile stimulation of fabric against human skin, we used the technology of functional magnetic resonance imaging (fMRI), to observe brain activation when the subjects touched silk fabric actively using fingers. Consistent with previous research about brain cognition on sensory stimulation, large activation in the primary somatosensory cortex (SI), the secondary somatosensory cortex (SII) and moto cortex, and little activation in the posterior insula cortex and Broca's Area were observed when the subjects touched silk fabric. The technology of fMRI is a promising tool to observe and characterize the brain cognition on the tactile stimulation of fabric quantitatively. The intensity and extent of activation in the brain regions, especially the primary somatosensory cortex (SI) and the secondary somatosensory cortex (SII), can represent the perception of stimulation of fabric quantitatively. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Frequency-Selective Attention in Auditory Scenes Recruits Frequency Representations Throughout Human Superior Temporal Cortex.

PubMed

Riecke, Lars; Peters, Judith C; Valente, Giancarlo; Kemper, Valentin G; Formisano, Elia; Sorger, Bettina

2017-05-01

A sound of interest may be tracked amid other salient sounds by focusing attention on its characteristic features including its frequency. Functional magnetic resonance imaging findings have indicated that frequency representations in human primary auditory cortex (AC) contribute to this feat. However, attentional modulations were examined at relatively low spatial and spectral resolutions, and frequency-selective contributions outside the primary AC could not be established. To address these issues, we compared blood oxygenation level-dependent (BOLD) responses in the superior temporal cortex of human listeners while they identified single frequencies versus listened selectively for various frequencies within a multifrequency scene. Using best-frequency mapping, we observed that the detailed spatial layout of attention-induced BOLD response enhancements in primary AC follows the tonotopy of stimulus-driven frequency representations-analogous to the "spotlight" of attention enhancing visuospatial representations in retinotopic visual cortex. Moreover, using an algorithm trained to discriminate stimulus-driven frequency representations, we could successfully decode the focus of frequency-selective attention from listeners' BOLD response patterns in nonprimary AC. Our results indicate that the human brain facilitates selective listening to a frequency of interest in a scene by reinforcing the fine-grained activity pattern throughout the entire superior temporal cortex that would be evoked if that frequency was present alone. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans.

PubMed

Bakken, Trygve E; Roddey, J Cooper; Djurovic, Srdjan; Akshoomoff, Natacha; Amaral, David G; Bloss, Cinnamon S; Casey, B J; Chang, Linda; Ernst, Thomas M; Gruen, Jeffrey R; Jernigan, Terry L; Kaufmann, Walter E; Kenet, Tal; Kennedy, David N; Kuperman, Joshua M; Murray, Sarah S; Sowell, Elizabeth R; Rimol, Lars M; Mattingsdal, Morten; Melle, Ingrid; Agartz, Ingrid; Andreassen, Ole A; Schork, Nicholas J; Dale, Anders M; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R; Jagust, William; Trojanowki, John Q; Toga, Arthur W; Beckett, Laurel; Green, Robert C; Saykin, Andrew J; Morris, John; Liu, Enchi; Montine, Tom; Gamst, Anthony; Thomas, Ronald G; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Harvey, Danielle; Kornak, John; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Bandy, Dan; Koeppe, Robert A; Foster, Norm; Reiman, Eric M; Chen, Kewei; Mathis, Chet; Cairns, Nigel J; Taylor-Reinwald, Lisa; Trojanowki, J Q; Shaw, Les; Lee, Virginia M Y; Korecka, Magdalena; Crawford, Karen; Neu, Scott; Foroud, Tatiana M; Potkin, Steven; Shen, Li; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Dolen, Sara; Schneider, Lon S; Pawluczyk, Sonia; Spann, Bryan M; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L; Lord, Joanne L; Johnson, Kris; Doody, Rachelle S; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S; Bell, Karen L; Morris, John C; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Mitsis, Effie; Romirowsky, Aliza; deToledo-Morrell, Leyla; Shah, Raj C; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; Kielb, Stephanie; Rusinek, Henry; de Leon, Mony J; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P Murali; Petrella, Jeffrey R; Coleman, R Edward; Arnold, Steven E; Karlawish, Jason H; Wolk, David; Smith, Charles D; Jicha, Greg; Hardy, Peter; Lopez, Oscar L; Oakley, MaryAnn; Simpson, Donna M; Porsteinsson, Anton P; Goldstein, Bonnie S; Martin, Kim; Makino, Kelly M; Ismail, M Saleem; Brand, Connie; Mulnard, Ruth A; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I; Lah, James J; Cellar, Janet S; Burns, Jeffrey M; Anderson, Heather S; Swerdlow, Russell H; Apostolova, Liana; Lu, Po H; Bartzokis, George; Silverman, Daniel H S; Graff-Radford, Neill R; Parfitt, Francine; Johnson, Heather; Farlow, Martin R; Hake, Ann Marie; Matthews, Brandy R; Herring, Scott; van Dyck, Christopher H; Carson, Richard E; MacAvoy, Martha G; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Ging-Yuek; Hsiung, Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristina; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A; Johnson, Keith A; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan; Belden, Christine; Jacobson, Sandra; Kowall, Neil; Killiany, Ronald; Budson, Andrew E; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O; Wolday, Saba; Bwayo, Salome K; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; Fletcher, Evan; Carmichael, Owen; Olichney, John; Kittur, Smita; Borrie, Michael; Lee, T-Y; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M; Potkin, Steven G; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W; Kataki, Maria; Zimmerman, Earl A; Celmins, Dzintra; Brown, Alice D; Pearlson, Godfrey D; Blank, Karen; Anderson, Karen; Santulli, Robert B; Schwartz, Eben S; Sink, Kaycee M; Williamson, Jeff D; Garg, Pradeep; Watkins, Franklin; Ott, Brian R; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J; Miller, Bruce L; Mintzer, Jacobo; Longmire, Crystal Flynn; Spicer, Kenneth; Finger, Elizabether; Rachinsky, Irina; Drost, Dick; Jernigan, Terry; McCabe, Connor; Grant, Ellen; Ernst, Thomas; Kuperman, Josh; Chung, Yoon; Murray, Sarah; Bloss, Cinnamon; Darst, Burcu; Pritchett, Lexi; Saito, Ashley; Amaral, David; DiNino, Mishaela; Eyngorina, Bella; Sowell, Elizabeth; Houston, Suzanne; Soderberg, Lindsay; Kaufmann, Walter; van Zijl, Peter; Rizzo-Busack, Hilda; Javid, Mohsin; Mehta, Natasha; Ruberry, Erika; Powers, Alisa; Rosen, Bruce; Gebhard, Nitzah; Manigan, Holly; Frazier, Jean; Kennedy, David; Yakutis, Lauren; Hill, Michael; Gruen, Jeffrey; Bosson-Heenan, Joan; Carlson, Heatherly

2012-03-06

Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P(combined) = 3.2 × 10(-8)). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10(-9)) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5' UTR of GPCPD1, glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception.

A protein with anion exchange properties found in the kidney proximal tubule.

PubMed

Soleimani, M; Bizal, G L; Anderson, C C

1993-09-01

One important mechanism for reabsorption of chloride in the kidney proximal tubule involves anion exchange of chloride for a base. Anion exchange transport systems in general demonstrate sensitivity to inhibition by disulfonic stilbenes, probenecid, furosemide, and the arginyl amino group modifier phenylglyoxal. Using disulfonic stilbene affinity chromatography, we have identified and partially purified a protein with anion exchanger properties in luminal membrane vesicles isolated from rabbit kidney cortex. This protein has a molecular weight of 162 kD. The binding of the 162 kD protein to the stilbene affinity matrix is inhibited by disulfonic stilbenes, probenecid, furosemide, and phenylglyoxal. Reconstitution of the proteins eluted from the affinity matrix into liposomes demonstrates anion exchange activity as assayed by radiolabeled chloride influx. Deletion of the 162 kD protein from the eluted mixture by probenecid diminishes the anion exchanger activity in the reconstituted liposomes. Further purification of the disulfonic stilbene column eluant by Econo-Pac Q ion exchange chromatography resulted in significant enrichment in 162 kD protein abundance and also anion exchange activity in reconstituted liposomes. The results of the above experiments strongly suggest that the 162 kD protein is an anion exchanger. Insight into the functional and molecular characteristics of this protein should provide important information about the mechanism(s) of chloride reabsorption in the kidney proximal tubule.

Representation of the Speech Effectors in the Human Motor Cortex: Somatotopy or Overlap?

ERIC Educational Resources Information Center

Takai, Osamu; Brown, Steven; Liotti, Mario

2010-01-01

Somatotopy within the orofacial region of the human motor cortex has been a central concept in interpreting the results of neuroimaging and transcranial magnetic stimulation studies of normal and disordered speech. Yet, somatotopy has been challenged by studies showing overlap among the effectors within the homunculus. In order to address this…

Capturing the temporal evolution of choice across prefrontal cortex

PubMed Central

Hunt, Laurence T; Behrens, Timothy EJ; Hosokawa, Takayuki; Wallis, Jonathan D; Kennerley, Steven W

2015-01-01

Activity in prefrontal cortex (PFC) has been richly described using economic models of choice. Yet such descriptions fail to capture the dynamics of decision formation. Describing dynamic neural processes has proven challenging due to the problem of indexing the internal state of PFC and its trial-by-trial variation. Using primate neurophysiology and human magnetoencephalography, we here recover a single-trial index of PFC internal states from multiple simultaneously recorded PFC subregions. This index can explain the origins of neural representations of economic variables in PFC. It describes the relationship between neural dynamics and behaviour in both human and monkey PFC, directly bridging between human neuroimaging data and underlying neuronal activity. Moreover, it reveals a functionally dissociable interaction between orbitofrontal cortex, anterior cingulate cortex and dorsolateral PFC in guiding cost-benefit decisions. We cast our observations in terms of a recurrent neural network model of choice, providing formal links to mechanistic dynamical accounts of decision-making. DOI: http://dx.doi.org/10.7554/eLife.11945.001 PMID:26653139

Midcingulate Motor Map and Feedback Detection: Converging Data from Humans and Monkeys.

PubMed

Procyk, Emmanuel; Wilson, Charles R E; Stoll, Frederic M; Faraut, Maïlys C M; Petrides, Michael; Amiez, Céline

2016-02-01

The functional and anatomical organization of the cingulate cortex across primate species is the subject of considerable and often confusing debate. The functions attributed to the midcingulate cortex (MCC) embrace, among others, feedback processing, pain, salience, action-reward association, premotor functions, and conflict monitoring. This multiplicity of functional concepts suggests either unresolved separation of functional contributions or integration and convergence. We here provide evidence from recent experiments in humans and from a meta-analysis of monkey data that MCC feedback-related activity is generated in the rostral cingulate premotor area by specific body maps directly related to the modality of feedback. As such, we argue for an embodied mechanism for adaptation and exploration in MCC. We propose arguments and precise tools to resolve the origins of performance monitoring signals in the medial frontal cortex, and to progress on issues regarding homology between human and nonhuman primate cingulate cortex. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hippocampus, perirhinal cortex, and complex visual discriminations in rats and humans

PubMed Central

Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.

2015-01-01

Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with perirhinal lesions were impaired and did not exhibit the normal preference for exploring the odd object. Notably, rats with hippocampal lesions exhibited the same impairment. Thus, the deficit is unlikely to illuminate functions attributed specifically to perirhinal cortex. Both lesion groups were able to acquire visual discriminations involving the same objects used in the oddity task. Patients with hippocampal damage or larger medial temporal lobe lesions were intact in a similar oddity task that allowed participants to explore objects quickly using eye movements. We suggest that humans were able to rely on an intact working memory capacity to perform this task, whereas rats (who moved slowly among the objects) needed to rely on long-term memory. PMID:25593294

Functional subregions of the human entorhinal cortex

PubMed Central

Maass, Anne; Berron, David; Libby, Laura A; Ranganath, Charan; Düzel, Emrah

2015-01-01

The entorhinal cortex (EC) is the primary site of interactions between the neocortex and hippocampus. Studies in rodents and nonhuman primates suggest that EC can be divided into subregions that connect differentially with perirhinal cortex (PRC) vs parahippocampal cortex (PHC) and with hippocampal subfields along the proximo-distal axis. Here, we used high-resolution functional magnetic resonance imaging at 7 Tesla to identify functional subdivisions of the human EC. In two independent datasets, PRC showed preferential intrinsic functional connectivity with anterior-lateral EC and PHC with posterior-medial EC. These EC subregions, in turn, exhibited differential connectivity with proximal and distal subiculum. In contrast, connectivity of PRC and PHC with subiculum followed not only a proximal-distal but also an anterior-posterior gradient. Our data provide the first evidence that the human EC can be divided into functional subdivisions whose functional connectivity closely parallels the known anatomical connectivity patterns of the rodent and nonhuman primate EC. DOI: http://dx.doi.org/10.7554/eLife.06426.001 PMID:26052749

Volition and conflict in human medial frontal cortex.

PubMed

Nachev, Parashkev; Rees, Geraint; Parton, Andrew; Kennard, Christopher; Husain, Masud

2005-01-26

Controversy surrounds the role of human medial frontal cortex in controlling actions. Although damage to this area leads to severe difficulties in spontaneously initiating actions, the precise mechanisms underlying such "volitional" deficits remain to be established. Previous studies have implicated the medial frontal cortex in conflict monitoring and the control of voluntary action, suggesting that these key processes are functionally related or share neural substrates. Here, we combine a novel behavioral paradigm with functional imaging of the oculomotor system to reveal, for the first time, a functional subdivision of the pre-supplementary motor area (pre-SMA) into anatomically distinct areas that respond exclusively to either volition or conflict. We also demonstrate that activity in the supplementary eye field (SEF) distinguishes between success and failure in changing voluntary action plans during conflict, suggesting a role for the SEF in implementing the resolution of conflicting actions. We propose a functional architecture of human medial frontal cortex that incorporates the generation of action plans and the resolution of conflict.

Disorders of fatty acid oxidation and autosomal recessive polycystic kidney disease-different clinical entities and comparable perinatal renal abnormalities.

PubMed

Hackl, Agnes; Mehler, Katrin; Gottschalk, Ingo; Vierzig, Anne; Eydam, Marcus; Hauke, Jan; Beck, Bodo B; Liebau, Max C; Ensenauer, Regina; Weber, Lutz T; Habbig, Sandra

2017-05-01

Differential diagnosis of prenatally detected hyperechogenic and enlarged kidneys can be challenging as there is a broad phenotypic overlap between several rare genetic and non-genetic disorders. Metabolic diseases are among the rarest underlying disorders, but they demand particular attention as their prognosis and postnatal management differ from those of other diseases. We report two cases of cystic, hyperechogenic and enlarged kidneys detected on prenatal ultrasound images, resulting in the suspected diagnosis of autosomal recessive polycystic kidney disease (ARPKD). Postnatal clinical course and work-up, however, revealed early, neonatal forms of disorders of fatty acid oxidation (DFAO) in both cases, namely, glutaric acidemia type II, based on identification of the novel, homozygous splice-site mutation c.1117-2A > G in the ETFDH gene, in one case and carnitine palmitoyltransferase II deficiency in the other case. Review of pre- and postnatal sonographic findings resulted in the identification of some important differences that might help to differentiate DFAO from ARPKD. In DFAO, kidneys are enlarged to a milder degree than in ARPKD, and the cysts are located ubiquitously, including also in the cortex and the subcapsular area. Interestingly, recent studies have pointed to a switch in metabolic homeostasis, referred to as the Warburg effect (aerobic glycolysis), as one of the underlying mechanisms of cell proliferation and cyst formation in cystic kidney disease. DFAO are characterized by the inhibition of oxidative phosphorylation, resulting in aerobic glycolysis, and thus they do resemble the Warburg effect. We therefore speculate that this inhibition might be one of the pathomechanisms of renal hyperproliferation and cyst formation in DFAO analogous to the reported findings in ARPKD. Neonatal forms of DFAO can be differentially diagnosed in neonates with cystic or hyperechogenic kidneys and necessitate immediate biochemical work-up to provide early metabolic management.

Successful Posttransplant Treatment of Hepatitis C With Ledipasvir-Sofosbuvir in HIV+ Kidney Transplant Recipients.

PubMed

Sawinski, Deirdre; Lee, Dong H; Doyle, Alden M; Blumberg, Emily A

2017-05-01

Ledipasvir-sofosbuvir is effective at eradicating hepatitis C virus (HCV) infection in the general population and in HCV-monoinfected kidney transplant recipients, but there are no data to guide its use in human immunodeficiency virus/HCV coinfected kidney transplant patients. We treated 6 human immunodeficiency virus/HCV coinfected kidney transplant recipients with ledipasvir-sofosbuvir at our 2 centers. All were infected with genotype 1 and 66% had received kidneys from HCV+ donors. All patients cleared the virus while on therapy and 100% have achieved a sustained virologic response at 12 weeks after completion of ledipasvir-sofosbuvir. Tacrolimus dosing required adjustment during and after ledipasvir-sofosbuvir therapy but antiretroviral regimens did not. Ledipasvir-sofosbuvir was well tolerated. Although all patients in our series were treated posttransplant, the ideal timing of HCV therapy in this population is unknown, and the impact of HCV clearance on posttransplant outcomes is yet to be determined.

Shiga Toxin Mediated Neurologic Changes in Murine Model of Disease.

PubMed

Pradhan, Suman; Pellino, Christine; MacMaster, Kayleigh; Coyle, Dennis; Weiss, Alison A

2016-01-01

Seizures and neurologic involvement have been reported in patients infected with Shiga toxin (Stx) producing E. coli , and hemolytic uremic syndrome (HUS) with neurologic involvement is associated with more severe outcome. We investigated the extent of renal and neurologic damage in mice following injection of the highly potent form of Stx, Stx2a, and less potent Stx1. As observed in previous studies, Stx2a brought about moderate to acute tubular necrosis of proximal and distal tubules in the kidneys. Brain sections stained with hematoxylin and eosin (H&E) appeared normal, although some red blood cell congestion was observed. Microglial cell responses to neural injury include up-regulation of surface-marker expression (e.g., Iba1) and stereotypical morphological changes. Mice injected with Stx2a showed increased Iba1 staining, mild morphological changes associated with microglial activation (thickening of processes), and increased microglial staining per unit area. Microglial changes were observed in the cortex, hippocampus, and amygdala regions, but not the nucleus. Magnetic resonance imaging (MRI) of Stx2a-treated mice revealed no hyper-intensities in the brain, although magnetic resonance spectroscopy (MRS) revealed significantly decreased levels of phosphocreatine in the thalamus. Less dramatic changes were observed following Stx1 challenge. Neither immortalized microvascular endothelial cells from the cerebral cortex of mice (bEnd.3) nor primary human brain microvascular endothelial cells were found to be susceptible to Stx1 or Stx2a. The lack of susceptibility to Stx for both cell types correlated with an absence of receptor expression. These studies indicate Stx causes subtle, but identifiable changes in the mouse brain.

Genome Sequence of Oxalobacter formigenes Strain HC-1

PubMed Central

Allison, Milton J.; Yu, Fahong; Farmerie, William

2017-01-01

ABSTRACT The lack of Oxalobacter formigenes colonization of the human gut has been correlated with the formation of calcium oxalate kidney stones and also with the number of recurrent kidney stone episodes. Here, we present the genome sequence of HC-1, a human strain isolated from an individual residing in Iowa, USA. PMID:28684568

Bardoxolone methyl prevents the development and progression of cardiac and renal pathophysiologies in mice fed a high-fat diet.

PubMed

Camer, Danielle; Yu, Yinghua; Szabo, Alexander; Wang, Hongqin; Dinh, Chi H L; Huang, Xu-Feng

2016-01-05

Obesity caused by the consumption of a high-fat (HF) diet is a major risk factor for the development of associated complications, such as heart and kidney failure. A semi-synthetic triterpenoid, bardoxolone methyl (BM) was administrated to mice fed a HF diet for 21 weeks to determine if it would prevent the development of obesity-associated cardiac and renal pathophysiologies. Twelve week old male C57BL/6J mice were fed a lab chow (LC), HF (40% fat), or a HF diet supplemented with 10 mg/kg/day BM in drinking water. After 21 weeks, the left ventricles of hearts and cortex of kidneys of mice were collected for analysis. Histological analysis revealed that BM prevented HF diet-induced development of structural changes in the heart and kidneys. BM prevented HF diet-induced decreases in myocyte number in cardiac tissue, although this treatment also elevated cardiac endothelin signalling molecules. In the kidneys, BM administration prevented HF diet-induced renal corpuscle hypertrophy and attenuated endothelin signalling. Furthermore, in both the hearts and kidneys of mice fed a HF diet, BM administration prevented HF diet-induced increases in fat accumulation, macrophage infiltration and tumour necrosis factor alpha (TNFα) gene expression. These findings suggest that BM prevents HF diet-induced developments of cardiac and renal pathophysiologies in mice fed a chronic HF diet by preventing inflammation. Moreover, these results suggest that BM has the potential as a therapeutic for preventing obesity-induced cardiac and renal pathophysiologies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Renal F4/80+CD11c+ Mononuclear Phagocytes Display Phenotypic and Functional Characteristics of Macrophages in Health and in Adriamycin Nephropathy

PubMed Central

Wang, Yiping; Wang, Xin Maggie; Lu, Junyu; Lee, Vincent W.S.; Ye, Qianling; Nguyen, Hanh; Zheng, Guoping; Zhao, Ye; Alexander, Stephen I.; Harris, David C.H.

2015-01-01

Conventional markers of macrophages (Mфs) and dendritic cells (DCs) lack specificity and often overlap, leading to confusion and controversy regarding the precise function of these cells in kidney and other diseases. This study aimed to identify the phenotype and function of renal mononuclear phagocytes (rMPs) expressing key markers of both Mфs and DCs. F4/80+CD11c+ cells accounted for 45% of total rMPs in normal kidneys and in those from mice with Adriamycin nephropathy (AN). Despite expression of the DC marker CD11c, these double-positive rMPs displayed the features of Mфs, including Mф-like morphology, high expression of CD68, CD204, and CD206, and high phagocytic ability but low antigen-presenting ability. F4/80+CD11c+ cells were found in the cortex but not in the medulla of the kidney. In AN, F4/80+CD11c+ cells displayed an M1 Mф phenotype with high expression of inflammatory mediators and costimulatory factors. Adoptive transfer of F4/80+CD11c+ cells separated from diseased kidney aggravated renal injury in AN mice. Furthermore, adoptive transfer of common progenitors revealed that kidney F4/80+CD11c+ cells were derived predominantly from monocytes, but not from pre-DCs. In conclusion, renal F4/80+CD11c+ cells are a major subset of rMPs and display Mф-like phenotypic and functional characteristics in health and in AN. PMID:25012165

Comparing kidney perfusion using noncontrast arterial spin labeling MRI and microsphere methods in an interventional swine model.

PubMed

Artz, Nathan S; Wentland, Andrew L; Sadowski, Elizabeth A; Djamali, Arjang; Grist, Thomas M; Seo, Songwon; Fain, Sean B

2011-02-01

The purpose of this study was to assess the ability of a flow-sensitive alternating inversion recovery-arterial spin labeling (FAIR-ASL) technique to track renal perfusion changes during pharmacologic and physiologic alterations in renal blood flow using microspheres as a gold standard. Fluorescent microsphere and FAIR-ASL perfusion were compared in the cortex of the kidney for 11 swine across 4 interventional time points: (1) under baseline conditions, (2) during an acetylcholine and fluid bolus challenge to increase perfusion, (3) initially after switching to isoflurane anesthesia, and (4) after 2 hours of isoflurane anesthesia. In 10 of the 11 swine, a bag of ice was placed on the hilum of 1 kidney at the beginning of isoflurane administration to further reduce perfusion in 1 kidney. Both ASL and microspheres tracked the expected cortical perfusion changes (P < 0.02) across the interventions, including an increase in perfusion during the acetylcholine challenge and decrease during the administration of isoflurane. Both techniques also measured lower cortical perfusion in the iced compared with the non-iced kidneys (P ≤ 0.01). The ASL values were systematically lower compared with microsphere perfusion. Very good correlation (r = 0.81, P < 0.0001) was observed between the techniques, and the relationship appeared linear for perfusion values in the expected physiologic range (microsphere perfusion <550 mL/min/100 g) although ASL values saturated for perfusion >550 mL/min/100 g. Cortical perfusion measured with ASL correlated with microspheres and reliably detected changes in renal perfusion in response to physiologic challenge.

Renal F4/80+ CD11c+ mononuclear phagocytes display phenotypic and functional characteristics of macrophages in health and in adriamycin nephropathy.

PubMed

Cao, Qi; Wang, Yiping; Wang, Xin Maggie; Lu, Junyu; Lee, Vincent W S; Ye, Qianling; Nguyen, Hanh; Zheng, Guoping; Zhao, Ye; Alexander, Stephen I; Harris, David C H

2015-02-01

Conventional markers of macrophages (Mфs) and dendritic cells (DCs) lack specificity and often overlap, leading to confusion and controversy regarding the precise function of these cells in kidney and other diseases. This study aimed to identify the phenotype and function of renal mononuclear phagocytes (rMPs) expressing key markers of both Mфs and DCs. F4/80(+)CD11c(+) cells accounted for 45% of total rMPs in normal kidneys and in those from mice with Adriamycin nephropathy (AN). Despite expression of the DC marker CD11c, these double-positive rMPs displayed the features of Mфs, including Mф-like morphology, high expression of CD68, CD204, and CD206, and high phagocytic ability but low antigen-presenting ability. F4/80(+)CD11c(+) cells were found in the cortex but not in the medulla of the kidney. In AN, F4/80(+)CD11c(+) cells displayed an M1 Mф phenotype with high expression of inflammatory mediators and costimulatory factors. Adoptive transfer of F4/80(+)CD11c(+) cells separated from diseased kidney aggravated renal injury in AN mice. Furthermore, adoptive transfer of common progenitors revealed that kidney F4/80(+)CD11c(+) cells were derived predominantly from monocytes, but not from pre-DCs. In conclusion, renal F4/80(+)CD11c(+) cells are a major subset of rMPs and display Mф-like phenotypic and functional characteristics in health and in AN. Copyright © 2015 by the American Society of Nephrology.

76 FR 11501 - National Institute of Diabetes and Digestive and Kidney Diseases

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis...

Face Encoding and Recognition in the Human Brain

NASA Astrophysics Data System (ADS)

Haxby, James V.; Ungerleider, Leslie G.; Horwitz, Barry; Maisog, Jose Ma.; Rapoport, Stanley I.; Grady, Cheryl L.

1996-01-01

A dissociation between human neural systems that participate in the encoding and later recognition of new memories for faces was demonstrated by measuring memory task-related changes in regional cerebral blood flow with positron emission tomography. There was almost no overlap between the brain structures associated with these memory functions. A region in the right hippocampus and adjacent cortex was activated during memory encoding but not during recognition. The most striking finding in neocortex was the lateralization of prefrontal participation. Encoding activated left prefrontal cortex, whereas recognition activated right prefrontal cortex. These results indicate that the hippocampus and adjacent cortex participate in memory function primarily at the time of new memory encoding. Moreover, face recognition is not mediated simply by recapitulation of operations performed at the time of encoding but, rather, involves anatomically dissociable operations.

Nitric Oxide Synthase and Neuronal NADPH Diaphorase are Identical in Brain and Peripheral Tissues

NASA Astrophysics Data System (ADS)

Dawson, Ted M.; Bredt, David S.; Fotuhi, Majid; Hwang, Paul M.; Snyder, Solomon H.

1991-09-01

NADPH diaphorase staining neurons, uniquely resistant to toxic insults and neurodegenerative disorders, have been colocalized with neurons in the brain and peripheral tissue containing nitric oxide synthase (EC 1.14.23.-), which generates nitric oxide (NO), a recently identified neuronal messenger molecule. In the corpus striatum and cerebral cortex, NO synthase immunoreactivity and NADPH diaphorase staining are colocalized in medium to large aspiny neurons. These same neurons colocalize with somatostatin and neuropeptide Y immunoreactivity. NO synthase immunoreactivity and NADPH diaphorase staining are colocalized in the pedunculopontine nucleus with choline acetyltransferase-containing cells and are also colocalized in amacrine cells of the inner nuclear layer and ganglion cells of the retina, myenteric plexus neurons of the intestine, and ganglion cells of the adrenal medulla. Transfection of human kidney cells with NO synthase cDNA elicits NADPH diaphorase staining. The ratio of NO synthase to NADPH diaphorase staining in the transfected cells is the same as in neurons, indicating that NO synthase fully accounts for observed NADPH staining. The identity of neuronal NO synthase and NADPH diaphorase suggests a role for NO in modulating neurotoxicity.

Mesenchymal stem cells cannot affect mRNA expression of toll-like receptors in different tissues during sepsis.

PubMed

Pedrazza, Leonardo; Pereira, Talita Carneiro Brandão; Abujamra, Ana Lucia; Nunes, Fernanda Bordignon; Bogo, Maurício Reis; de Oliveira, Jarbas Rodrigues

2017-07-01

Experimental animal models and human clinical studies support a crucial role for TLRs in infectious diseases. The aim of this study was to test the ability of MSCs, which have immunomodulatory effects, of altering the mRNA expression of toll-like receptors during a experimental model of sepsis in different tissues. Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 10 6 cells/animal). Lungs, cortex, kidney, liver and colon tissue were dissected after 12 h of sepsis induction and TLR2/3/4/9 mRNA were evaluated by RT-qPCR. We observed a decrease of TLR2 and 9 mRNA expression in the liver of the sepsis group, while TLR3 was decreased in the lung and liver. No change was found between the sepsis group and the sepsis + MSC group. In this model of experimental sepsis the MSCs were unable to modify the mRNA expression of the different toll-like receptors evaluated.

Trans-proximal tubular steady-state concentration differences studied by micro-puncture and tissue content of sodium and chloride at varying intraluminal sodium concentrations in vitro in rat kidney cortex slices: evidence for a multisite sodium transport system.

PubMed Central

Györy, A Z; Roby, H

1977-01-01

1. With the aid of micropuncture techniques, proximal tubular transepithelial concentration differences for Na (deltaC Na) and chloride (deltaC Cl) were measured in kidney cortex slices at bathing fluid Na concentrations from 10 to 400 m-mole. kg-1. Tissue content of water, Na and K was also measured in such slices. Under steady-state conditions of zero net flux of NaCl and water, deltaC Na represents the sum of active Na transport, factored by the tubular permeability coefficient added to a component of flux due to electrical forces. 2. The relation between bathing fluid Na concentraton and deltaC Na appeared sigmoid in form suggesting an allosteric mechanism for the transport step. 3. Transtubular potential difference, calculated from transepithelial Cl distribution ratios, did not appear constant at the various bathing fluid Na concentrations. Correcting for the effect of these potential differences on the value of each deltaC Na did not convert the sigmoid transport curve to a hyperbolic one, confirming the suggested allosteric nature of the active Na transport step. 4. Intracellular Na content varied linearly with bathing fluid Na concentrations implying free entry of this cation into the cell. This also suggests that the sigmoid transport curve is related to the properties of the active Na transport pump. PMID:856986

Nephroprotective Effect of Sonchus oleraceus Extract against Kidney Injury Induced by Ischemia-Reperfusion in Wistar Rats

PubMed Central

Torres-González, Liliana; Cienfuegos-Pecina, Eduardo; Perales-Quintana, Marlene M.; Muñoz-Espinosa, Linda E.; Pérez-Rodríguez, Edelmiro

2018-01-01

Introduction Kidney ischemia-reperfusion (I/R) injury is the main cause of delayed graft function in solid organ transplantation. Sonchus oleraceus is a plant with well-known antioxidant and anti-inflammatory activities; however, its effects on renal I/R are unknown. Objective To evaluate whether S. oleraceus extract (S.O.e.) has nephroprotective activity in an I/R model in Wistar rats. Materials and Methods Animal groups (n = 6): sham, I/R (45 min/15 h), S.O.e (300 mg/kg p.o.), and S.O.e + I/R (300 mg/kg, p.o.; 45 min/15 h). Renal function, proinflammatory cytokines, alanine aminotransferase, markers of oxidative stress, and histology were evaluated. Results None of the mediators evaluated differed significantly between the S.O.e and sham groups. Levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and proinflammatory cytokines were higher, and superoxide dismutase (SOD) was lower in the I/R group than in the sham group. Histology showed tubular epithelial necrosis in the medulla and cortex in the I/R group. In the S.O.e + I/R group, S.O.e pretreatment attenuated the I/R-induced increases in BUN, creatinine, MDA, and proinflammatory cytokines induced, SOD was maintained, and histology showed discontinuous necrosis in the medulla but no necrosis in the cortex. Conclusions S.O.e was neither hepatotoxic nor nephrotoxic. S.O.e. pretreatment showed a nephroprotective effect against I/R. PMID:29643981

Nephroprotective Effect of Sonchus oleraceus Extract against Kidney Injury Induced by Ischemia-Reperfusion in Wistar Rats.

PubMed

Torres-González, Liliana; Cienfuegos-Pecina, Eduardo; Perales-Quintana, Marlene M; Alarcon-Galvan, Gabriela; Muñoz-Espinosa, Linda E; Pérez-Rodríguez, Edelmiro; Cordero-Pérez, Paula

2018-01-01

Kidney ischemia-reperfusion (I/R) injury is the main cause of delayed graft function in solid organ transplantation. Sonchus oleraceus is a plant with well-known antioxidant and anti-inflammatory activities; however, its effects on renal I/R are unknown. To evaluate whether S. oleraceus extract (S.O.e.) has nephroprotective activity in an I/R model in Wistar rats. Animal groups ( n = 6): sham, I/R (45 min/15 h), S.O.e (300 mg/kg p.o.), and S.O.e + I/R (300 mg/kg, p.o.; 45 min/15 h). Renal function, proinflammatory cytokines, alanine aminotransferase, markers of oxidative stress, and histology were evaluated. None of the mediators evaluated differed significantly between the S.O.e and sham groups. Levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and proinflammatory cytokines were higher, and superoxide dismutase (SOD) was lower in the I/R group than in the sham group. Histology showed tubular epithelial necrosis in the medulla and cortex in the I/R group. In the S.O.e + I/R group, S.O.e pretreatment attenuated the I/R-induced increases in BUN, creatinine, MDA, and proinflammatory cytokines induced, SOD was maintained, and histology showed discontinuous necrosis in the medulla but no necrosis in the cortex. S.O.e was neither hepatotoxic nor nephrotoxic. S.O.e. pretreatment showed a nephroprotective effect against I/R.

Creatine synthesis: production of guanidinoacetate by the rat and human kidney in vivo.

PubMed

Edison, Erica E; Brosnan, Margaret E; Meyer, Christian; Brosnan, John T

2007-12-01

A fraction of the body's creatine and creatine phosphate spontaneously degrades to creatinine, which is excreted by the kidneys. In humans, this amounts to approximately 1-2 g/day and demands a comparable rate of de novo creatine synthesis. This is a two-step process in which l-arginine:glycine amidinotransferase (AGAT) catalyzes the conversion of glycine and arginine to ornithine and guanidinoacetate (GAA); guanidinoacetate methyltransferase (GAMT) then catalyzes the S-adenosylmethionine-dependent methylation of GAA to creatine. AGAT is found in the kidney and GAMT in the liver, which implies an interorgan movement of GAA from the kidney to the liver. We studied the renal production of this metabolite in both rats and humans. In control rats, [GAA] was 5.9 microM in arterial plasma and 10.9 microM in renal venous plasma for a renal arteriovenous (A-V) difference of -5.0 microM. In the rat, infusion of arginine or citrulline markedly increased renal GAA production but infusion of glycine did not. Rats fed 0.4% creatine in their diet had decreased renal AGAT activity and mRNA, an arterial plasma [GAA] of 1.5 microM, and a decreased renal A-V difference for GAA of -0.9 microM. In humans, [GAA] was 2.4 microM in arterial plasma, with a renal A-V difference of -1.1 microM. These studies show, for the first time, that GAA is produced by both rat and human kidneys in vivo.

Vitamin D in the Pathophysiology of Hypertension, Kidney Disease, and Diabetes: Examining the Relationship Between Vitamin D and the Renin-Angiotensin System in Human Diseases

PubMed Central

Vaidya, Anand; Williams, Jonathan S.

2011-01-01

Objective Vitamin D has been implicated in the pathophysiology of extra-skeletal conditions such as hypertension, kidney disease, and diabetes, via its ability to negatively regulate the renin-angiotensin system (RAS). This article reviews the evidence supporting a link between vitamin D and the RAS in these conditions, with specific emphasis on translational observations and their limitations. Methods Literature review of animal and human studies evaluating the role of vitamin D in hypertension, kidney disease, and diabetes. Results Excess activity of the RAS has been implicated in the pathogenesis of hypertension, chronic kidney disease, decreased insulin secretion, and insulin resistance. Animal studies provide strong support for 1,25(OH)2D mediated down-regulation of renin expression and RAS activity via its interaction with the vitamin D receptor. Furthermore, the activity of vitamin D metabolites in animals is associated with reductions in blood pressure, proteinuria and renal injury, and with improved β–cell function. Many observational, and a few interventional, studies in humans have supported these findings; however, there is a lack of well designed prospective human interventional studies to definitively assess clinical outcomes. Conclusion Animal studies implicate vitamin D receptor agonist therapy to lower RAS activity as a potential method to reduce the risk of hypertension, kidney disease, and diabetes. There is a need for more well designed prospective interventional studies to validate this hypothesis in human clinical outcomes. PMID:22075270

Functional involvement of the organic cation transporter 2 (rOct2) in the renal uptake of organic cations in rats.

PubMed

Umehara, K-I; Iwatsubo, T; Noguchi, K; Kamimura, H

2008-01-01

This study examined the contribution made by organic cation transporters (hOCT/rOct) to the saturable component of the renal uptake of 1-methyl-4-phenylpyridinium, tetraethylammonium (TEA), cimetidine and metformin into rOct2-expressing HEK293 cells and rat kidney slices. All the test compounds accumulated in the rat kidney slices in a carrier-mediated manner. The Michaelis- Menten constant (K(m)) values for saturable uptake of TEA, cimetidine and metformin into rat kidney slices were relatively comparable with those for the rOct2-expressing HEK293 cells. In addition, the relative uptake activity values of TEA, cimetidine and metformin in rat kidney slices were similar to those in rOct2-expressing HEK293 cells. This suggests that the saturable components involved in the renal uptake of TEA, cimetidine and metformin are mediated mainly by rOct2. The saturable uptake profile of cationic compounds into rat kidney can be evaluated in both cDNA-expressing cells and rat kidney slices, as well as the transporter expression pattern. This approach can also be used to estimate the saturable uptake mechanism of cationic compounds into the human kidney when human kidney slices and hOCT2-expressing cells are used.

In vivo regulation of the heme oxygenase-1 gene in humanized transgenic mice

PubMed Central

Kim, Junghyun; Zarjou, Abolfazl; Traylor, Amie M.; Bolisetty, Subhashini; Jaimes, Edgar A.; Hull, Travis D.; George, James F.; Mikhail, Fady M.; Agarwal, Anupam

2012-01-01

Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme degradation producing equimolar amounts of carbon monoxide, iron, and biliverdin. Induction of HO-1 is a beneficial response to tissue injury in diverse animal models of diseases including acute kidney injury. In vitro analysis has shown that the human HO-1 gene is transcriptionally regulated by changes in chromatin conformation but whether such control occurs in vivo is not known. To enable such analysis, we generated transgenic mice, harboring an 87-kb bacterial artificial chromosome expressing human HO-1 mRNA and protein and bred these mice with HO-1 knockout mice to generate humanized BAC transgenic mice. This successfully rescued the phenotype of the knockout mice including reduced birth rates, tissue iron overload, splenomegaly, anemia, leukocytosis, dendritic cell abnormalities and survival after acute kidney injury induced by rhabdomyolysis or cisplatin nephrotoxicity. Transcription factors such as USF1/2, JunB, Sp1, and CTCF were found to associate with regulatory regions of the human HO-1 gene in the kidney following rhabdomyolysis. Chromosome Conformation Capture and ChIP-loop assays confirmed this in the formation of chromatin looping in vivo. Thus, these bacterial artificial chromosome humanized HO-1 mice are a valuable model to study the human HO-1 gene providing insight to the in vivo architecture of the gene in acute kidney injury and other diseases. PMID:22495295

Anodal Transcranial Direct Current Stimulation Reduces Psychophysically Measured Surround Suppression in the Human Visual Cortex

PubMed Central

Spiegel, Daniel P.; Hansen, Bruce C.; Byblow, Winston D.; Thompson, Benjamin

2012-01-01

Transcranial direct current stimulation (tDCS) is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN), was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex. PMID:22563485

Global Image Dissimilarity in Macaque Inferotemporal Cortex Predicts Human Visual Search Efficiency

PubMed Central

Sripati, Arun P.; Olson, Carl R.

2010-01-01

Finding a target in a visual scene can be easy or difficult depending on the nature of the distractors. Research in humans has suggested that search is more difficult the more similar the target and distractors are to each other. However, it has not yielded an objective definition of similarity. We hypothesized that visual search performance depends on similarity as determined by the degree to which two images elicit overlapping patterns of neuronal activity in visual cortex. To test this idea, we recorded from neurons in monkey inferotemporal cortex (IT) and assessed visual search performance in humans using pairs of images formed from the same local features in different global arrangements. The ability of IT neurons to discriminate between two images was strongly predictive of the ability of humans to discriminate between them during visual search, accounting overall for 90% of the variance in human performance. A simple physical measure of global similarity – the degree of overlap between the coarse footprints of a pair of images – largely explains both the neuronal and the behavioral results. To explain the relation between population activity and search behavior, we propose a model in which the efficiency of global oddball search depends on contrast-enhancing lateral interactions in high-order visual cortex. PMID:20107054

Immunohistochemical Markers of Neural Progenitor Cells in the Early Embryonic Human Cerebral Cortex

PubMed Central

Vinci, L.; Ravarino, A.; Fanos, V.; Naccarato, A.G.; Senes, G.; Gerosa, C.; Bevilacqua, G.; Faa, G.; Ambu, R.

2016-01-01

The development of the human central nervous system represents a delicate moment of embryogenesis. The purpose of this study was to analyze the expression of multiple immunohistochemical markers in the stem/progenitor cells in the human cerebral cortex during the early phases of development. To this end, samples from cerebral cortex were obtained from 4 human embryos of 11 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained with several markers including GFAP, WT1, Nestin, Vimentin, CD117, S100B, Sox2, PAX2, PAX5, Tβ4, Neurofilament, CD44, CD133, Synaptophysin and Cyclin D1. Our study shows the ability of the different immunohistochemical markers to evidence different zones of the developing human cerebral cortex, allowing the identification of the multiple stages of differentiation of neuronal and glial precursors. Three important markers of radial glial cells are evidenced in this early gestational age: Vimentin, Nestin and WT1. Sox2 was expressed by the stem/progenitor cells of the ventricular zone, whereas the postmitotic neurons of the cortical plate were immunostained by PAX2 and NSE. Future studies are needed to test other important stem/progenitor cells markers and to better analyze differences in the immunohistochemical expression of these markers during gestation. PMID:26972711

Extension of a PBPK model for ethylene glycol and glycolic acid to include the competitive formation and clearance of metabolites associated with kidney toxicity in rats and humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Corley, R.A., E-mail: rick.corley@pnl.gov; Saghir, S.A.; Bartels, M.J.

2011-02-01

A previously developed PBPK model for ethylene glycol and glycolic acid was extended to include glyoxylic acid, oxalic acid, and the precipitation of calcium oxalate that is associated with kidney toxicity in rats and humans. The development and evaluation of the PBPK model was based upon previously published pharmacokinetic studies coupled with measured blood and tissue partition coefficients and rates of in vitro metabolism of glyoxylic acid to oxalic acid, glycine and other metabolites using primary hepatocytes isolated from male Wistar rats and humans. Precipitation of oxalic acid with calcium in the kidneys was assumed to occur only at concentrationsmore » exceeding the thermodynamic solubility product for calcium oxalate. This solubility product can be affected by local concentrations of calcium and other ions that are expressed in the model using an ion activity product estimated from toxicity studies such that calcium oxalate precipitation would be minimal at dietary exposures below the NOAEL for kidney toxicity in the sensitive male Wistar rat. The resulting integrated PBPK predicts that bolus oral or dietary exposures to ethylene glycol would result in typically 1.4-1.6-fold higher peak oxalate levels and 1.6-2-fold higher AUC's for calcium oxalate in kidneys of humans as compared with comparably exposed male Wistar rats over a dose range of 1-1000 mg/kg. The converse (male Wistar rats predicted to have greater oxalate levels in the kidneys than humans) was found for inhalation exposures although no accumulation of calcium oxalate is predicted to occur until exposures are well in excess of the theoretical saturated vapor concentration of 200 mg/m{sup 3}. While the current model is capable of such cross-species, dose, and route-of-exposure comparisons, it also highlights several areas of potential research that will improve confidence in such predictions, especially at low doses relevant for most human exposures.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

McAfee, J.G.; Krauss, D.J.; Subramanian, G.

The 3-hour biodistribution of /sup 99m/Tc complexes of five diphosphonates (HMDP, NMMDP, DMAD, DPD, and APD), imidodiphosphonate (IDP), and pyrophosphate (PYP) was compared in rats with segmental renal infarction induced by a 1-hour occlusion of a renal artery branch. /sup 95m/Tc labeled MDP was a reference substance in all animals. Three agents (APD, HMDP and IDP) had a higher infarct/normal kidney concentration ratio than MDP, the latter two by virtue of a lower content in normal kidney. HMDP, DPD, and IDP had very high liver concentrations. DPD showed relatively high concentrations in soft tissues and blood. The blood and kidneymore » levels of PYP were higher than those of MDP but the infarct/normal kidney ratios were similar. None of the agents had a higher uptake in bone than MDP: four had a significantly lower uptake. The increased concentration of /sup 99m/Tc MDP in the infarcts was readily seen in camera images one day after renal artery occlusion, but not at three or seven days. Increased diphosphonate uptake was accompanied by an influx of calcium in both cortex and medulla. The accumulation of diphosphonate in areas of infarction was not modified by infusions of verapamil or Captopril.« less

Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit

PubMed Central

Ishimoto, Hitoshi

2011-01-01

Continuous efforts have been devoted to unraveling the biophysiology and development of the human fetal adrenal cortex, which is structurally and functionally unique from other species. It plays a pivotal role, mainly through steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation. The steroidogenic activity is characterized by early transient cortisol biosynthesis, followed by its suppressed synthesis until late gestation, and extensive production of dehydroepiandrosterone and its sulfate, precursors of placental estrogen, during most of gestation. The gland rapidly grows through processes including cell proliferation and angiogenesis at the gland periphery, cellular migration, hypertrophy, and apoptosis. Recent studies employing modern technologies such as gene expression profiling and laser capture microdissection have revealed that development and/or function of the fetal adrenal cortex may be regulated by a panoply of molecules, including transcription factors, extracellular matrix components, locally produced growth factors, and placenta-derived CRH, in addition to the primary regulator, fetal pituitary ACTH. The role of the fetal adrenal cortex in human pregnancy and parturition appears highly complex, probably due to redundant and compensatory mechanisms regulating these events. Mounting evidence indicates that actions of hormones operating in the human feto-placental unit are likely mediated by mechanisms including target tissue responsiveness, local metabolism, and bioavailability, rather than changes only in circulating levels. Comprehensive study of such molecular mechanisms and the newly identified factors implicated in adrenal development should help crystallize our understanding of the development and physiology of the human fetal adrenal cortex. PMID:21051591

Four decades of kidney transplantation in Cuba.

PubMed

Alfonzo, Jorge P

2013-01-01

This article describes the background, beginnings, development, evolution and outcomes of kidney transplantation in Cuba. Nephrology as a medical specialty in Cuba began in 1962 and was formalized in 1966. Conditions were created to implement renal replacement therapy (including transplants), bring nephrology care to the entire country and train human resources who would assume this responsibility, making Cuba one of the first countries with a comprehensive program for renal patient care. After three unsuccessful cadaveric-donor kidney transplantations in 1968-69, the ensuing history of kidney transplantation can be summarized in the following three stages. 1970-1975: In January 1970, cadaveric-donor kidney transplantation began at the Nephrology Institute. That year, 17 kidney transplantations were performed; four of these patients lived with functional kidneys for 15-25 years; 10-year graft survival was 23.5% (Kaplan-Meier survival curve); HLA typing began in 1974. By December 1975, 170 grafts had been done in three hospitals. 1976-1985: Seven transplantation centers performed 893 grafts during this period. HLA-DR typing was introduced in 1976 and the National Histocompatibility Laboratory Network was founded in 1978. The first related living-donor kidney transplantation was done in 1979. 1986-2011: The National Kidney Transplantation Coordinating Center and the National Kidney Transplantation Program were created in 1986; the first combined kidney-pancreas transplantation was performed the same year. In 1990, cyclosporine and the Cuban monoclonal antibody IOR-T3 were introduced for immunosuppression to prevent rejection, as were other Cuban products (hepatitis B vaccine and recombinant human erythropoietin) for transplant patients. By December 2011, the cumulative number of transplants was 4636 (384 from related living donors). With over 40 years of experience, kidney transplantation is now well established in Cuba; it is free and universally accessible, on the basis of need and appropriateness.

Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction

PubMed Central

ASAHINA, Makoto; SHIMIZU, Fumi; OHTA, Masayuki; TAKEYAMA, Michiyasu; TOZAWA, Ryuichi

2015-01-01

Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome. PMID:25912321

Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction.

PubMed

Asahina, Makoto; Shimizu, Fumi; Ohta, Masayuki; Takeyama, Michiyasu; Tozawa, Ryuichi

2015-01-01

Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome.

Functional Human Podocytes Generated in Organoids from Amniotic Fluid Stem Cells

PubMed Central

Benedetti, Valentina; Novelli, Rubina; Abbate, Mauro; Rizzo, Paola; Conti, Sara; Tomasoni, Susanna; Corna, Daniela; Pozzobon, Michela; Cavallotti, Daniela; Yokoo, Takashi; Morigi, Marina; Benigni, Ariela; Remuzzi, Giuseppe

2016-01-01

Generating kidney organoids using human stem cells could offer promising prospects for research and therapeutic purposes. However, no cell-based strategy has generated nephrons displaying an intact three-dimensional epithelial filtering barrier. Here, we generated organoids using murine embryonic kidney cells, and documented that these tissues recapitulated the complex three-dimensional filtering structure of glomerular slits in vivo and accomplished selective glomerular filtration and tubular reabsorption. Exploiting this technology, we mixed human amniotic fluid stem cells with mouse embryonic kidney cells to establish three-dimensional chimeric organoids that engrafted in vivo and grew to form vascularized glomeruli and tubular structures. Human cells contributed to the formation of glomerular structures, differentiated into podocytes with slit diaphragms, and internalized exogenously infused BSA, thus attaining in vivo degrees of specialization and function unprecedented for donor stem cells. In conclusion, human amniotic fluid stem cell chimeric organoids may offer new paths for studying renal development and human podocyte disease, and for facilitating drug discovery and translational research. PMID:26516208

Formation of tamoxifen-DNA adducts in multiple organs of adult female cynomolgus monkeys dosed with tamoxifen for 30 days.

PubMed

Schild, Laura J; Divi, Rao L; Beland, Frederick A; Churchwell, Mona I; Doerge, Daniel R; Gamboa da Costa, Gonçalo; Marques, M Matilde; Poirier, Miriam C

2003-09-15

The use of the antiestrogen tamoxifen (TAM) is associated with an increase in endometrial cancer. TAM-induced endometrial carcinogenesis may proceed through a genotoxin-mediated pathway, although the detection of endometrial TAM-DNA adducts in exposed women is still controversial. In this study, a monkey model has been used to investigate the question of TAM-DNA adduct formation in primates. Two methods have been used to determine TAM-DNA adducts: a TAM-DNA chemiluminescence immunoassay (TAM-DNA CIA), using an antiserum that has specificity for (E)-alpha-(deoxyguanosin-N(2)-yl)-tamoxifen (dG-TAM) and (E)-alpha-(deoxyguanosin-N(2)-yl)-N-desmethyltamoxifen (dG-desmethyl-TAM) and electrospray ionization tandem mass spectrometry (ES-MS/MS) coupled with on-line sample preparation and high-performance liquid chromatography (HPLC). Mature (19 year old) cynomolgus monkeys were given either vehicle control (n = 1) or TAM (n = 3) twice daily for a total dose of 2 mg of TAM/kg body weight (bw)/day for 30 days by naso-gastric intubation. Tissues were harvested, and DNA was isolated from uterus, ovary, liver, brain cortex, and kidney. By TAM-DNA CIA, values for uterine TAM-DNA adducts in two monkeys were 0.9 and 1.7 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts in the same animals were 0.4 and 0.5 adducts/10(8) nucleotides. Liver, brain cortex, and kidney DNA samples from the three exposed monkeys had TAM-DNA levels of 2.1-4.2 adducts/10(8) nucleotides, 0.4-5.0 adducts/10(8) nucleotides, and 0.7-2.1 adducts/10(8) nucleotides, respectively. By HPLC-ES-MS/MS, the levels of TAM-DNA adducts detected in all tissues were comparable with those observed by TAM-DNA CIA. Thus, values for uterine TAM-DNA adducts ranged from 0.5 to 1.4 adducts/10(8) nucleotides, whereas values for ovarian TAM-DNA adducts, measurable in two monkeys, were 0.2 and 0.3 adducts/10(8) nucleotides. Liver DNA contained the highest TAM-DNA adduct levels (7.0-11.1 adducts/10(8) nucleotides), whereas brain cortex DNA contained lower adduct levels (0.6-4.8 adducts/10(8) nucleotides) and the lowest levels were measured in the kidney (0.2-0.4 adducts/10(8) nucleotides). This study indicates that cynomolgus monkeys are capable of metabolizing TAM to genotoxic intermediates that form TAM-DNA adducts in multiple tissues.

Preprocessing of emotional visual information in the human piriform cortex.

PubMed

Schulze, Patrick; Bestgen, Anne-Kathrin; Lech, Robert K; Kuchinke, Lars; Suchan, Boris

2017-08-23

This study examines the processing of visual information by the olfactory system in humans. Recent data point to the processing of visual stimuli by the piriform cortex, a region mainly known as part of the primary olfactory cortex. Moreover, the piriform cortex generates predictive templates of olfactory stimuli to facilitate olfactory processing. This study fills the gap relating to the question whether this region is also capable of preprocessing emotional visual information. To gain insight into the preprocessing and transfer of emotional visual information into olfactory processing, we recorded hemodynamic responses during affective priming using functional magnetic resonance imaging (fMRI). Odors of different valence (pleasant, neutral and unpleasant) were primed by images of emotional facial expressions (happy, neutral and disgust). Our findings are the first to demonstrate that the piriform cortex preprocesses emotional visual information prior to any olfactory stimulation and that the emotional connotation of this preprocessing is subsequently transferred and integrated into an extended olfactory network for olfactory processing.

Computational Image Analysis Reveals Intrinsic Multigenerational Differences between Anterior and Posterior Cerebral Cortex Neural Progenitor Cells

PubMed Central

Winter, Mark R.; Liu, Mo; Monteleone, David; Melunis, Justin; Hershberg, Uri; Goderie, Susan K.; Temple, Sally; Cohen, Andrew R.

2015-01-01

Summary Time-lapse microscopy can capture patterns of development through multiple divisions for an entire clone of proliferating cells. Images are taken every few minutes over many days, generating data too vast to process completely by hand. Computational analysis of this data can benefit from occasional human guidance. Here we combine improved automated algorithms with minimized human validation to produce fully corrected segmentation, tracking, and lineaging results with dramatic reduction in effort. A web-based viewer provides access to data and results. The improved approach allows efficient analysis of large numbers of clones. Using this method, we studied populations of progenitor cells derived from the anterior and posterior embryonic mouse cerebral cortex, each growing in a standardized culture environment. Progenitors from the anterior cortex were smaller, less motile, and produced smaller clones compared to those from the posterior cortex, demonstrating cell-intrinsic differences that may contribute to the areal organization of the cerebral cortex. PMID:26344906

Understanding the Dorsal and Ventral Systems of the Human Cerebral Cortex: Beyond Dichotomies

ERIC Educational Resources Information Center

Borst, Gregoire; Thompson, William L.; Kosslyn, Stephen M.

2011-01-01

Traditionally, characterizations of the macrolevel functional organization of the human cerebral cortex have focused on the left and right cerebral hemispheres. However, the idea of left brain versus right brain functions has been shown to be an oversimplification. We argue here that a top-bottom divide, rather than a left-right divide, is a more…

Perception and Action Selection Dissociate Human Ventral and Dorsal Cortex

ERIC Educational Resources Information Center

Ikkai, Akiko; Jerde, Trenton A.; Curtis, Clayton E.

2011-01-01

We test theories about the functional organization of the human cortex by correlating brain activity with demands on perception versus action selection. Subjects covertly searched for a target among an array of 4, 8, or 12 items (perceptual manipulation) and then, depending on the color of the array, made a saccade toward, away from, or at a right…

Electroencephalogram evidence for the activation of human mirror neuron system during the observation of intransitive shadow and line drawing actions☆

PubMed Central

Zhu, Huaping; Sun, Yaoru; Wang, Fang

2013-01-01

Previous studies have demonstrated that hand shadows may activate the motor cortex associated with the mirror neuron system in human brain. However, there is no evidence of activity of the human mirror neuron system during the observation of intransitive movements by shadows and line drawings of hands. This study examined the suppression of electroencephalography mu waves (8–13 Hz) induced by observation of stimuli in 18 healthy students. Three stimuli were used: real hand actions, hand shadow actions and actions made by line drawings of hands. The results showed significant desynchronization of the mu rhythm (“mu suppression”) across the sensorimotor cortex (recorded at C3, Cz and C4), the frontal cortex (recorded at F3, Fz and F4) and the central and right posterior parietal cortex (recorded at Pz and P4) under all three conditions. Our experimental findings suggest that the observation of “impoverished hand actions”, such as intransitive movements of shadows and line drawings of hands, is able to activate widespread cortical areas related to the putative human mirror neuron system. PMID:25206595

Laterality and the evolution of the prefronto-cerebellar system in anthropoids.

PubMed

Smaers, Jeroen B; Steele, James; Case, Charleen R; Amunts, Katrin

2013-06-01

There is extensive evidence for an early vertebrate origin of lateralized motor behavior and of related asymmetries in underlying brain systems. We investigate human lateralized motor functioning in a broad comparative context of evolutionary neural reorganization. We quantify evolutionary trends in the fronto-cerebellar system (involved in motor learning) across 46 million years of divergent primate evolution by comparing rates of evolution of prefrontal cortex, frontal motor cortex, and posterior cerebellar hemispheres along individual branches of the primate tree of life. We provide a detailed evolutionary model of the neuroanatomical changes leading to modern human lateralized motor functioning, demonstrating an increased role for the fronto-cerebellar system in the apes dating to their evolutionary divergence from the monkeys (∼30 million years ago (Mya)), and a subsequent shift toward an increased role for prefrontal cortex over frontal motor cortex in the fronto-cerebellar system in the Homo-Pan ancestral lineage (∼10 Mya) and in the human ancestral lineage (∼6 Mya). We discuss these results in the context of cortico-cerebellar functions and their likely role in the evolution of human tool use and speech. © 2013 New York Academy of Sciences.

Functional correlates of the anterolateral processing hierarchy in human auditory cortex.

PubMed

Chevillet, Mark; Riesenhuber, Maximilian; Rauschecker, Josef P

2011-06-22

Converging evidence supports the hypothesis that an anterolateral processing pathway mediates sound identification in auditory cortex, analogous to the role of the ventral cortical pathway in visual object recognition. Studies in nonhuman primates have characterized the anterolateral auditory pathway as a processing hierarchy, composed of three anatomically and physiologically distinct initial stages: core, belt, and parabelt. In humans, potential homologs of these regions have been identified anatomically, but reliable and complete functional distinctions between them have yet to be established. Because the anatomical locations of these fields vary across subjects, investigations of potential homologs between monkeys and humans require these fields to be defined in single subjects. Using functional MRI, we presented three classes of sounds (tones, band-passed noise bursts, and conspecific vocalizations), equivalent to those used in previous monkey studies. In each individual subject, three regions showing functional similarities to macaque core, belt, and parabelt were readily identified. Furthermore, the relative sizes and locations of these regions were consistent with those reported in human anatomical studies. Our results demonstrate that the functional organization of the anterolateral processing pathway in humans is largely consistent with that of nonhuman primates. Because our scanning sessions last only 15 min/subject, they can be run in conjunction with other scans. This will enable future studies to characterize functional modules in human auditory cortex at a level of detail previously possible only in visual cortex. Furthermore, the approach of using identical schemes in both humans and monkeys will aid with establishing potential homologies between them.

Analysis of internal structure changes in black human hair keratin fibers resulting from bleaching treatments using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Kuzuhara, Akio

2013-09-01

In order to investigate in detail the internal structure changes in virgin black human hair keratin fibers resulting from bleaching treatments, the structure of cross-sections at various depths of black human hair, which had been impossible due to high melanin grande content, was directly analyzed using Raman spectroscopy. The gauche-gauche-gauche (GGG) content of the sbnd SSsbnd groups existing from the cuticle region to the center of cortex region of the virgin black human hair remarkably decreased, while the gauche-gauche-trans and trans-gauche-trans contents were not changed by performing the excessive bleaching treatment. In particular, it was found that not only the β-sheet and/or random coil content, but also the α-helix content existing throughout the cortex region of virgin black human hair decreased. In addition, the transmission electron microscope observation shows that the proteins in the cell membrane complex, the cuticle and cortex of the virgin black human hair were remarkably eluted by performing the excessive bleaching treatment. From these experiments, the author concluded that the sbnd SSsbnd groups, which have a GGG conformation were decomposed and finally converted to cysteic acid, and the α-helix structure of some of the proteins existing in the keratin was changed to the random coil structure, or eluted from the cortex region, thereby leading to the reduction in the protein density of the virgin human hair after the excessive bleaching treatment.

Kidney biomimicry--a rediscovered scientific field that could provide hope to patients with kidney disease.

PubMed

Stenvinkel, Peter; Johnson, Richard J

2013-11-01

Most studies on kidney disease have relied on classic experimental studies in mice and rats or clinical studies in humans. From such studies much understanding of the physiology and pathophysiology of kidney disease has been obtained. However, breakthroughs in the prevention and treatment of kidney diseases have been relatively few, and new approaches to fight kidney disease are needed. Here we discuss kidney biomimicry as a new approach to understand kidney disease. Examples are given of how various animals have developed ways to prevent or respond to kidney failure, how to protect themselves from hypoxia or oxidative stress and from the scourge of hyperglycemia. We suggest that investigation of evolutionary biology and comparative physiology might provide new insights for the prevention and treatment of kidney disease. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

[Morphological and laminar distribution of cholecystokinin-immunoreactive neurons in cortex of human inferior parietal lobe and their clinical significance].

PubMed

Puskas, Laslo; Draganić-Gajić, Saveta; Malobabić, Slobodan; Puskas, Nela; Krivokuća, Dragan; Stanković, Gordana

2008-01-01

Cholecystocinine is a neuropeptide whose function in the cortex has not yet been clarified, although its relation with some psychic disorders has been noticed. Previous studies have not provided detailed data about types, or arrangement of neurons that contain those neuropeptide in the cortex of human inferior parietal lobe. The aim of this study was to examine precisely the morphology and typography of neurons containing cholecytocinine in the human cortex of inferior parietal lobule. There were five human brains on which we did the immunocystochemical research of the shape and laminar distribution of cholecystocinine immunoreactive neurons on serial sections of supramarginal gyrus and angular gyrus. The morphological analysis of cholecystocinine-immunoreactive neurons was done on frozen sections using avidin-biotin technique, by antibody to cholecystocinine diluted in the proportion 1:6000 using diamine-benzedine. Cholecystocinine immunoreactive neurons were found in the first three layers of the cortex of inferior parietal lobule, and their densest concentration was in the 2nd and 3rd layer. The following types of neurons were found: bipolar neurons, then its fusiform subtype, Cajal-Retzius neurons (in the 1st layer), reverse pyramidal (triangular) and unipolar neurons. The diameters of some types of neurons were from 15 to 35 microm, and the diameters of dendritic arborization were from 85-207 microm. A special emphasis is put on the finding of Cajal-Retzius neurons that are immunoreactive to cholecystocinine, which demands further research. Bearing in mind numerous clinical studies pointing out the role of cholecystokinine in the pathogenesis of schizophrenia, the presence of a great number of cholecystokinine immunoreactive neurons in the cortex of inferior parietal lobule suggests their role in the pathogenesis of schizophrenia.

OBscure but not OBsolete: Perturbations of the frontal cortex in common between rodent olfactory bulbectomy model and major depression.

PubMed

Rajkumar, Ramamoorthy; Dawe, Gavin S

2018-04-07

Olfactory bulbectomy (OBX) has been used as a model of depression over several decades. This model presupposes a mechanism that is still not proven in clinical depression. A wealth of clinical literature has focused on the derangements in frontal cortex (prefrontal, orbitofrontal and anterior cingulate cortices) associated with depression. In this comprehensive review, anatomical, electrophysiological and molecular sequelae of bulbectomy in the rodent frontal cortex are explored and compared with findings on brains of humans with major depression. Certain commonalities in neurobiological features of the perturbed frontal cortex in the bulbectomised rodent and the depressed human brain are evident. Also, meta-analysis reports on clinical studies on depressed patients provide prima facie evidence that perturbations in the frontal cortex are associated with major depression. Analysing the pattern of perturbations in the chemical neuroanatomy of the frontal cortex will contribute to understanding of the neurobiology of depression. Revisiting the OBX model of depression to examine these neurobiological changes in frontal cortex with contemporary imaging, proteomics, lipidomics, metabolomics and epigenomics technologies is proposed as an approach to enhance the translational value of this animal model to facilitate identification of targets and biomarkers for clinical depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Noninvasive studies of human visual cortex using neuromagnetic techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aine, C.J.; George, J.S.; Supek, S.

1990-01-01

The major goals of noninvasive studies of the human visual cortex are: to increase knowledge of the functional organization of cortical visual pathways; and to develop noninvasive clinical tests for the assessment of cortical function. Noninvasive techniques suitable for studies of the structure and function of human visual cortex include magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission tomography (SPECT), scalp recorded event-related potentials (ERPs), and event-related magnetic fields (ERFs). The primary challenge faced by noninvasive functional measures is to optimize the spatial and temporal resolution of the measurement and analytic techniques in order to effectively characterizemore » the spatial and temporal variations in patterns of neuronal activity. In this paper we review the use of neuromagnetic techniques for this purpose. 8 refs., 3 figs.« less

Cognition, emotion, and the alcohol--aggression relationship: comment on Giancola (2000).

PubMed

Lyvers, M

2000-11-01

P. R. Giancola's (2000) thesis that the alcohol-aggression relationship can be explained by alcohol-induced disruption of executive cognitive functions mediated by the prefrontal cortex is critically examined. At moderate doses, alcohol has been reported to increase aggression in animals as diverse as fish, rats, cats, monkeys, and humans. Although alcohol depresses prefrontal cortex activity and disrupts executive cognitive performance in humans, alcohol's anxiolytic actions, and its disinhibiting effects on subcortical structures implicated in anger and aggression, may be at least as important as the higher cognitive functions cited by Giancola in accounting for the alcohol-aggression relationship. Other drugs that alter prefrontal cortex activity have also been reported to influence aggressive responding in humans and other animals, and implications of this are briefly discussed.

78 FR 64509 - National Institute of Diabetes and Digestive and Kidney Diseases; Amended Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis...

78 FR 64519 - National Institute of Diabetes and Digestive and Kidney Diseases; Amended Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis...

78 FR 36203 - National Institute of Diabetes and Digestive and Kidney Diseases; Amended Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis...

Strong human leukocyte antigen matching effect in nonsensitized kidney recipients with high pretransplant soluble CD30.

PubMed

Süsal, Caner; Pelzl, Steffen; Opelz, Gerhard

2003-10-27

The influence of human leukocyte antigen (HLA) matching on graft survival is greater in patients with preformed lymphocytotoxic antibodies than in nonsensitized patients. Pretransplant serum soluble CD30 (sCD30) affects graft outcome independently of presensitization status. The impact of HLA compatibility on kidney transplant survival was analyzed in 3980 nonsensitized first cadaveric kidney recipients in relation to the pretransplant serum sCD30 content. Although HLA compatibility influenced graft outcome only marginally in nonsensitized recipients with low sCD30 (at 3 years: P=0.0095; at 5 years: P=0.1033), a strong HLA matching effect was observed in nonsensitized recipients with high sCD30 (at 3 years: P<0.0001; at 5 years: P=0.0001). Nonsensitized patients with high pretransplant sCD30 benefit from an HLA well-matched kidney. Patients should be tested for sCD30 while on the waiting list for a kidney transplant, and HLA well-matched kidneys should be allocated to patients with high sCD30.

Kidney cell electrophoresis in space flight: Rationale, methods, results and flow cytometry applications

NASA Technical Reports Server (NTRS)

Todd, P.; Morrison, Dennis R.; Barlow, Grant H.; Lewis, Marian L.; Lanham, J. W.; Cleveland, C.; Williams, K.; Kunze, M. E.; Goolsby, C. L.

1988-01-01

Cultures of human embryonic kidney cells consistently contain an electrophoretically separable subpopulation of cells that produce high levels of urokinase and have an electrophoretic mobility about 85 percent as high as that of the most mobile human embryonic kidney cells. This subpopulation is rich in large epithelioid cells that have relatively little internal structure. When resolution and throughput are adequate, free fluid electrophoresis can be used to isolate a broad band of low mobility cells which also produces high levels of plasminogen activators (PAs). In the course of performing this, it was discovered that all electrophoretic subpopulations of cultured human embryonic kidney cells produce some PAs and that separate subpopulations produce high quantities of different types of PA's. This information and the development of sensitive assays for this project have provided new insights into cell secretion mechanisms related to fibrinolysis. These advances would probably not have been made without the NASA program to explore fundamental questions of free fluid electrophoresis in space.

Neural Pathways Conveying Novisual Information to the Visual Cortex

PubMed Central

2013-01-01

The visual cortex has been traditionally considered as a stimulus-driven, unimodal system with a hierarchical organization. However, recent animal and human studies have shown that the visual cortex responds to non-visual stimuli, especially in individuals with visual deprivation congenitally, indicating the supramodal nature of the functional representation in the visual cortex. To understand the neural substrates of the cross-modal processing of the non-visual signals in the visual cortex, we firstly showed the supramodal nature of the visual cortex. We then reviewed how the nonvisual signals reach the visual cortex. Moreover, we discussed if these non-visual pathways are reshaped by early visual deprivation. Finally, the open question about the nature (stimulus-driven or top-down) of non-visual signals is also discussed. PMID:23840972

Serial and Parallel Processing in the Primate Auditory Cortex Revisited

PubMed Central

Recanzone, Gregg H.; Cohen, Yale E.

2009-01-01

Over a decade ago it was proposed that the primate auditory cortex is organized in a serial and parallel manner in which there is a dorsal stream processing spatial information and a ventral stream processing non-spatial information. This organization is similar to the “what”/“where” processing of the primate visual cortex. This review will examine several key studies, primarily electrophysiological, that have tested this hypothesis. We also review several human imaging studies that have attempted to define these processing streams in the human auditory cortex. While there is good evidence that spatial information is processed along a particular series of cortical areas, the support for a non-spatial processing stream is not as strong. Why this should be the case and how to better test this hypothesis is also discussed. PMID:19686779

Regional distribution of neuropeptide Y mRNA in postmortem human brain.

PubMed

Brené, S; Lindefors, N; Kopp, J; Sedvall, G; Persson, H

1989-12-01

The distribution of messenger RNA encoding neuropeptide Y (NPY) was studied in 11 different postmortem human brain regions using in situ hybridization histochemistry, and RNA blot analysis. In situ hybridization data revealed that the highest numerical density of labeled cells corresponded to neurons in accumbens area, caudate nucleus, putamen, and substantia innominata. Significantly fewer NPY mRNA-containing neurons were found in frontal and parietal cortex, amygdaloid body and dentate gyrus. No NPY mRNA-containing cells were found in substantia nigra. NPY mRNA-positive neurons from all regions studied showed relatively similar labeling, as revealed by computerized image analysis. Blot analysis showed an approximately 0.8 kb NPY mRNA in all brain regions studied, except in substantia nigra and cerebellum. Densitometric scanning of the autoradiograms revealed levels of NPY mRNA in the following order: putamen greater than caudate nucleus greater than frontal cortex (Brodmann areas 4 and 6) greater than temporal cortex (Brodmann area 38) greater than parietal cortex (Brodmann areas 5 and 7) greater than frontal cortex (Brodmann area 11). Hence, although NPY mRNA is widely distributed in neurons of the human brain large regional variation exists, with the highest expression in accumbens area and parts of the basal ganglia.

Simultaneous Expression from Both the Sense and Antisense Strand of the Erythropoietin Receptor Gene Mitigates Acute Lung Injury

DTIC Science & Technology

2017-09-01

Toronto) which immunoprecipitates EpoR but works poorly in immunoblots and not at in immunohistochemistry (Hu et al., Kidney Int. 2013 Sep;84(3):468-81...DAPI EpoR/GFP/DAPIGFP/DAPI C.. Ba/F32EpoR2Flag2GFP.cells 9 Figure 4. Screening the new MAbs to human RopE. Human embryonic kidney -293 (HEK-293) cells...ontogeny of EpoR and RopE expression Figure 7. Concordant RopE and EpoR expression was observed in the lung (left) and the kidney (right) that increase

Not the Usual Viral Suspects: Parvovirus B19, West Nile Virus, and Human T-Cell Lymphotrophic Virus Infections After Kidney Transplantation.

PubMed

Razonable, Raymund R

2016-09-01

Kidney transplant recipients are at increased risk of developing clinical disease due to uncommon opportunistic viral pathogens. Refractory anemia is classically associated with parvovirus B19 infection. West Nile virus has the propensity to cause fever and neurologic symptoms, while spastic paresis and lymphoma can be triggered by human T cell lymphotrophic virus. In this review article, the epidemiology, clinical manifestations, diagnosis and treatment of less common viruses are discussed in the setting of kidney transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Dissociable neural responses to hands and non-hand body parts in human left extrastriate visual cortex.

PubMed

Bracci, Stefania; Ietswaart, Magdalena; Peelen, Marius V; Cavina-Pratesi, Cristiana

2010-06-01

Accumulating evidence points to a map of visual regions encoding specific categories of objects. For example, a region in the human extrastriate visual cortex, the extrastriate body area (EBA), has been implicated in the visual processing of bodies and body parts. Although in the monkey, neurons selective for hands have been reported, in humans it is unclear whether areas selective for individual body parts such as the hand exist. Here, we conducted two functional MRI experiments to test for hand-preferring responses in the human extrastriate visual cortex. We found evidence for a hand-preferring region in left lateral occipitotemporal cortex in all 14 participants. This region, located in the lateral occipital sulcus, partially overlapped with left EBA, but could be functionally and anatomically dissociated from it. In experiment 2, we further investigated the functional profile of hand- and body-preferring regions by measuring responses to hands, fingers, feet, assorted body parts (arms, legs, torsos), and non-biological handlike stimuli such as robotic hands. The hand-preferring region responded most strongly to hands, followed by robotic hands, fingers, and feet, whereas its response to assorted body parts did not significantly differ from baseline. By contrast, EBA responded most strongly to body parts, followed by hands and feet, and did not significantly respond to robotic hands or fingers. Together, these results provide evidence for a representation of the hand in extrastriate visual cortex that is distinct from the representation of other body parts.

Dissociable Neural Responses to Hands and Non-Hand Body Parts in Human Left Extrastriate Visual Cortex

PubMed Central

Ietswaart, Magdalena; Peelen, Marius V.; Cavina-Pratesi, Cristiana

2010-01-01

Accumulating evidence points to a map of visual regions encoding specific categories of objects. For example, a region in the human extrastriate visual cortex, the extrastriate body area (EBA), has been implicated in the visual processing of bodies and body parts. Although in the monkey, neurons selective for hands have been reported, in humans it is unclear whether areas selective for individual body parts such as the hand exist. Here, we conducted two functional MRI experiments to test for hand-preferring responses in the human extrastriate visual cortex. We found evidence for a hand-preferring region in left lateral occipitotemporal cortex in all 14 participants. This region, located in the lateral occipital sulcus, partially overlapped with left EBA, but could be functionally and anatomically dissociated from it. In experiment 2, we further investigated the functional profile of hand- and body-preferring regions by measuring responses to hands, fingers, feet, assorted body parts (arms, legs, torsos), and non-biological handlike stimuli such as robotic hands. The hand-preferring region responded most strongly to hands, followed by robotic hands, fingers, and feet, whereas its response to assorted body parts did not significantly differ from baseline. By contrast, EBA responded most strongly to body parts, followed by hands and feet, and did not significantly respond to robotic hands or fingers. Together, these results provide evidence for a representation of the hand in extrastriate visual cortex that is distinct from the representation of other body parts. PMID:20393066

Behavioral and neurophysiological correlates of regret in rat decision-making on a neuroeconomic task

PubMed Central

Steiner, Adam P.; Redish, A. David

2014-01-01

Summary Disappointment entails the recognition that one did not get the value one expected. In contrast, regret entails the recognition that an alternate (counterfactual) action would have produced a more valued outcome. Thus, the key to identifying regret is the representation of that counterfactual option in situations in which a mistake has been made. In humans, the orbitofrontal cortex is active during expressions of regret, and humans with damage to the orbitofrontal cortex do not express regret. In rats and non-human primates, both the orbitofrontal cortex and the ventral striatum have been implicated in decision-making, particularly in representations of expectations of reward. In order to examine representations of regretful situations, we recorded neural ensembles from orbitofrontal cortex and ventral striatum in rats encountering a spatial sequence of wait/skip choices for delayed delivery of different food flavors. We were able to measure preferences using an economic framework. Rats occasionally skipped low-cost choices and then encountered a high-cost choice. This sequence economically defines a potential regret-inducing instance. In these situations, rats looked backwards towards the lost option, the cells within the orbitofrontal cortex and ventral striatum represented that missed action, rats were more likely to wait for the long delay, and rats rushed through eating the food after that delay. That these situations drove rats to modify their behavior suggests that regret-like processes modify decision-making in non-human mammals. PMID:24908102

Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report.

PubMed

Rahyussalim, Ahmad Jabir; Saleh, Ifran; Kurniawati, Tri; Lutfi, Andi Praja Wira Yudha

2017-11-30

Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the field of regenerative medicine allowed development of cell therapies suitable for kidney repair. Mesenchymal stem cell studies in animal models of chronic renal failure have uncovered a unique potential of these cells for improving function and regenerating the damaged kidney. We report a case of a 62-year-old ethnic Indonesian woman previously diagnosed as having thoracic spinal cord entrapment with paraplegic condition and chronic renal failure on hemodialysis. She had diabetes mellitus that affected her kidneys and had chronic renal failure for 2 years, with creatinine level of 11 mg/dl, and no urinating since then. She was treated with human umbilical cord mesenchymal stem cell implantation protocol. This protocol consists of implantation of 16 million human umbilical cord mesenchymal stem cells intrathecally and 16 million human umbilical cord mesenchymal stem cells intravenously. Three weeks after first intrathecal and intravenous implantation she could move her toes and her kidney improved. Her creatinine level decreased to 9 mg/dl. Now after 8 months she can raise her legs and her creatinine level is 2 mg/dl with normal urinating. Human umbilical cord mesenchymal stem cell implantations led to significant improvement for spinal cord entrapment and kidney failure. The major histocompatibility in allogeneic implantation is an important issue to be addressed in the future.

Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders

PubMed Central

Ronconi, Elisa; Angelotti, Maria Lucia; Peired, Anna; Mazzinghi, Benedetta; Becherucci, Francesca; Conti, Sara; Sansavini, Giulia; Sisti, Alessandro; Ravaglia, Fiammetta; Lombardi, Duccio; Provenzano, Aldesia; Manonelles, Anna; Cruzado, Josep M.; Giglio, Sabrina; Roperto, Rosa Maria; Materassi, Marco; Lasagni, Laura

2015-01-01

The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. PMID:25568173

The Relationship between Maternal Nutrition during Pregnancy and Offspring Kidney Structure and Function in Humans: A Systematic Review

PubMed Central

Lee, Yu Qi; Collins, Clare E.; Gordon, Adrienne; Rae, Kym M.; Pringle, Kirsty G.

2018-01-01

The intrauterine environment is critical for fetal growth and organ development. Evidence from animal models indicates that the developing kidney is vulnerable to suboptimal maternal nutrition and changes in health status. However, evidence from human studies are yet to be synthesised. Therefore, the aim of the current study was to systematically review current research on the relationship between maternal nutrition during pregnancy and offspring kidney structure and function in humans. A search of five databases identified 9501 articles, of which three experimental and seven observational studies met the inclusion criteria. Nutrients reviewed to date included vitamin A (n = 3), folate and vitamin B12 (n = 2), iron (n = 1), vitamin D (n = 1), total energy (n = 2) and protein (n = 1). Seven studies were assessed as being of “positive” and three of “neutral” quality. A variety of populations were studied, with limited studies investigating maternal nutrition during pregnancy, while measurements of offspring kidney outcomes were diverse across studies. There was a lack of consistency in the timing of follow-up for offspring kidney structure and/or function assessments, thus limiting comparability between studies. Deficiencies in maternal folate, vitamin A, and total energy during pregnancy were associated with detrimental impacts on kidney structure and function, measured by kidney volume, proteinuria, eGFRcystC and mean creatinine clearance in the offspring. Additional experimental and longitudinal prospective studies are warranted to confirm this relationship, especially in Indigenous populations where the risk of renal disease is greater. PMID:29466283

Human Induced Pluripotent Stem Cell-Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation.

PubMed

Sharmin, Sazia; Taguchi, Atsuhiro; Kaku, Yusuke; Yoshimura, Yasuhiro; Ohmori, Tomoko; Sakuma, Tetsushi; Mukoyama, Masashi; Yamamoto, Takashi; Kurihara, Hidetake; Nishinakamura, Ryuichi

2016-06-01

Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator-like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in vitro These induced human podocytes exhibited apicobasal polarity, with nephrin proteins accumulated close to the basal domain, and possessed primary processes that were connected with slit diaphragm-like structures. Microarray analysis of sorted iPS cell-derived podocytes identified well conserved marker gene expression previously shown in mouse and human podocytes in vivo Furthermore, we developed a novel transplantation method using spacers that release the tension of host kidney capsules, thereby allowing the effective formation of glomeruli from human iPS cell-derived nephron progenitors. The human glomeruli were vascularized with the host mouse endothelial cells, and iPS cell-derived podocytes with numerous cell processes accumulated around the fenestrated endothelial cells. Therefore, the podocytes generated from iPS cells retain the podocyte-specific molecular and structural features, which will be useful for dissecting human glomerular development and diseases. Copyright © 2016 by the American Society of Nephrology.

Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation

PubMed Central

Sharmin, Sazia; Taguchi, Atsuhiro; Kaku, Yusuke; Yoshimura, Yasuhiro; Ohmori, Tomoko; Sakuma, Tetsushi; Mukoyama, Masashi; Yamamoto, Takashi; Kurihara, Hidetake

2016-01-01

Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in vitro. These induced human podocytes exhibited apicobasal polarity, with nephrin proteins accumulated close to the basal domain, and possessed primary processes that were connected with slit diaphragm–like structures. Microarray analysis of sorted iPS cell–derived podocytes identified well conserved marker gene expression previously shown in mouse and human podocytes in vivo. Furthermore, we developed a novel transplantation method using spacers that release the tension of host kidney capsules, thereby allowing the effective formation of glomeruli from human iPS cell–derived nephron progenitors. The human glomeruli were vascularized with the host mouse endothelial cells, and iPS cell–derived podocytes with numerous cell processes accumulated around the fenestrated endothelial cells. Therefore, the podocytes generated from iPS cells retain the podocyte-specific molecular and structural features, which will be useful for dissecting human glomerular development and diseases. PMID:26586691

The kidneys in the Bible: what happened?

PubMed

Eknoyan, Garabed

2005-12-01

The kidneys, always used in the plural (kelayot), are mentioned more than 30 times in the Bible. In the Pentateuch, the kidneys are cited 11 times in the detailed instructions given for the sacrificial offering of animals at the altar. Whereas those instructions were for purification ceremonies at the Temple, sacrificial offerings were made subsequently in seeking divine intervention for the relief of medical problems. In the books of the Bible that follow the Pentateuch, mostly in Jeremiah and Psalms, the human kidneys are cited figuratively as the site of temperament, emotions, prudence, vigor, and wisdom. In five instances, they are mentioned as the organs examined by God to judge an individual. They are cited either before or after but always in conjunction with the heart as mirrors of the psyche of the person examined. There is also reference to the kidneys as the site of divine punishment for misdemeanors, committed or perceived, particularly in the book of Job, whose suffering and ailments are legendary. In the first vernacular versions of the Bible in English, the translators elected to use the term "reins" instead of kidneys in differentiating the metaphoric uses of human kidneys from that of their mention as anatomic organs of sacrificial animals burned at the altar. This initial effort at linguistic purity or gentility has progressed further in recent versions of the Bible, in which the reins are now replaced by the soul or the mind. The erosion may have begun in the centuries that followed the writing of the Bible, when recognition of the kidneys as excretory organs deprived them of the ancient aura of mysterious organs hidden deep in the body but accessible to the look of God. At approximately the same time, Greek analytical philosophy argued that the brain, which is never mentioned in the Bible, was the most divine and sacred part of the body. This argument gained ground in the past century, when the functions of the brain were elucidated, and ultimately established in the 1960s, when salvaging the kidneys for transplantation necessitated a change in the definition of death as irreversible brain function. It is ironic that advances in understanding kidney function and in nephrology that made kidney transplantation feasible may have contributed, albeit indirectly, to the gradual elimination of the metaphoric mention of human kidneys in the Bible.

Incidence and mortality of kidney cancer and its relationship with HDI (Human Development Index) in the world in 2012.

PubMed

Mohammadian, Maryam; Pakzad, Reza; Towhidi, Farhad; Makhsosi, Behnam Reza; Ahmadi, Abbas; Salehiniya, Hamid

2017-01-01

Kidney cancer is among the cancers that have the highest growth rate in all age and racial groups in the world and is as the most deadly type of urinary tract cancer. Since awareness about this cancer incidence status and mortality is essential for better planning, this study aimed to investigate the incidence and mortality rate of kidney cancer and its relationship with the development index in the world in 2012. This study was an ecological study conducted based on GLOBOCAN project of the World Health Organization (WHO) for the countries in the world. The correlation between Standardized Incidence Rates (SIRs) and Standardized Mortality Rates (SMRs) of kidney cancer with HDI and its components was assessed using SPSS18. In total, 337,860 incidence cases (213,924 were men and 123,936 women) and 143,406 deaths (90,802 cases in men and 52,604 in women) of kidney cancer were recorded in 2012. A positive correlation of 0.731 was seen between SIR of kidney cancer and HDI (p≤0.001). Also, a negative correlation of 0.627 was seen between SMR of kidney cancer and HDI (p≤0.001). The incidence and mortality rate of kidney cancer is higher in developed countries. A significant positive correlation has been seen between the standardized incidence and mortality rate of kidney cancer with the Human Development Index and its components. We need more studies to examine variation in incidence and mortality of kidney cancer and its related factors in the world.

[Neuroanatomy of Frontal Association Cortex].

PubMed

Takada, Masahiko

2016-11-01

The frontal association cortex is composed of the prefrontal cortex and the motor-related areas except the primary motor cortex (i.e., the so-called higher motor areas), and is well-developed in primates, including humans. The prefrontal cortex receives and integrates large bits of diverse information from the parietal, temporal, and occipital association cortical areas (termed the posterior association cortex), and paralimbic association cortical areas. This information is then transmitted to the primary motor cortex via multiple motor-related areas. Given these facts, it is likely that the prefrontal cortex exerts executive functions for behavioral control. The functional input pathways from the posterior and paralimbic association cortical areas to the prefrontal cortex are classified primarily into six groups. Cognitive signals derived from the prefrontal cortex are conveyed to the rostral motor-related areas to transform them into motor signals, which finally enter the primary motor cortex via the caudal motor-related areas. Furthermore, it has been shown that, similar to the primary motor cortex, areas of the frontal association cortex form individual networks (known as "loop circuits") with the basal ganglia and cerebellum via the thalamus, and hence are extensively involved in the expression and control of behavioral actions.

Hyperproteic diet and pregnancy of rat.

PubMed

Greco, A M; Sticchi, R; Gambardella, P; D'Aponte, D; Ferrante, P

1986-01-01

We have studied the effects of a purified diet enriched with animal protein (casein 40%, lactalbumin 20%) on different stages of rat pregnancy. We observed that hyperproteic diet, especially when administered from the first day of pregnancy, induces morphological alterations of liver, adrenal cortex, heart and kidney. Moreover, haematic dosages, carried out on 15th day of pregnancy, have shown moderate but significant increase of glucose and triglycerides and significant decrease of circulating aldosterone and corticosterone as well. Finally an early administration of hyperproteic diet causes less numerous litters and high mortality rate at birth.

Metabolomics Reveals Signature of Mitochondrial Dysfunction in Diabetic Kidney Disease

PubMed Central

Karl, Bethany; Mathew, Anna V.; Gangoiti, Jon A.; Wassel, Christina L.; Saito, Rintaro; Pu, Minya; Sharma, Shoba; You, Young-Hyun; Wang, Lin; Diamond-Stanic, Maggie; Lindenmeyer, Maja T.; Forsblom, Carol; Wu, Wei; Ix, Joachim H.; Ideker, Trey; Kopp, Jeffrey B.; Nigam, Sanjay K.; Cohen, Clemens D.; Groop, Per-Henrik; Barshop, Bruce A.; Natarajan, Loki; Nyhan, William L.; Naviaux, Robert K.

2013-01-01

Diabetic kidney disease is the leading cause of ESRD, but few biomarkers of diabetic kidney disease are available. This study used gas chromatography-mass spectrometry to quantify 94 urine metabolites in screening and validation cohorts of patients with diabetes mellitus (DM) and CKD(DM+CKD), in patients with DM without CKD (DM–CKD), and in healthy controls. Compared with levels in healthy controls, 13 metabolites were significantly reduced in the DM+CKD cohorts (P≤0.001), and 12 of the 13 remained significant when compared with the DM–CKD cohort. Many of the differentially expressed metabolites were water-soluble organic anions. Notably, organic anion transporter-1 (OAT1) knockout mice expressed a similar pattern of reduced levels of urinary organic acids, and human kidney tissue from patients with diabetic nephropathy demonstrated lower gene expression of OAT1 and OAT3. Analysis of bioinformatics data indicated that 12 of the 13 differentially expressed metabolites are linked to mitochondrial metabolism and suggested global suppression of mitochondrial activity in diabetic kidney disease. Supporting this analysis, human diabetic kidney sections expressed less mitochondrial protein, urine exosomes from patients with diabetes and CKD had less mitochondrial DNA, and kidney tissues from patients with diabetic kidney disease had lower gene expression of PGC1α (a master regulator of mitochondrial biogenesis). We conclude that urine metabolomics is a reliable source for biomarkers of diabetic complications, and our data suggest that renal organic ion transport and mitochondrial function are dysregulated in diabetic kidney disease. PMID:23949796

Laser Capture Microdissection and Multiplex-Tandem PCR Analysis of Proximal Tubular Epithelial Cell Signaling in Human Kidney Disease

PubMed Central

Wilkinson, Ray; Wang, Xiangju; Kassianos, Andrew J.; Zuryn, Steven; Roper, Kathrein E.; Osborne, Andrew; Sampangi, Sandeep; Francis, Leo; Raghunath, Vishwas; Healy, Helen

2014-01-01

Interstitial fibrosis, a histological process common to many kidney diseases, is the precursor state to end stage kidney disease, a devastating and costly outcome for the patient and the health system. Fibrosis is historically associated with chronic kidney disease (CKD) but emerging evidence is now linking many forms of acute kidney disease (AKD) with the development of CKD. Indeed, we and others have observed at least some degree of fibrosis in up to 50% of clinically defined cases of AKD. Epithelial cells of the proximal tubule (PTEC) are central in the development of kidney interstitial fibrosis. We combine the novel techniques of laser capture microdissection and multiplex-tandem PCR to identify and quantitate “real time” gene transcription profiles of purified PTEC isolated from human kidney biopsies that describe signaling pathways associated with this pathological fibrotic process. Our results: (i) confirm previous in-vitro and animal model studies; kidney injury molecule-1 is up-regulated in patients with acute tubular injury, inflammation, neutrophil infiltration and a range of chronic disease diagnoses, (ii) provide data to inform treatment; complement component 3 expression correlates with inflammation and acute tubular injury, (iii) identify potential new biomarkers; proline 4-hydroxylase transcription is down-regulated and vimentin is up-regulated across kidney diseases, (iv) describe previously unrecognized feedback mechanisms within PTEC; Smad-3 is down-regulated in many kidney diseases suggesting a possible negative feedback loop for TGF-β in the disease state, whilst tight junction protein-1 is up-regulated in many kidney diseases, suggesting feedback interactions with vimentin expression. These data demonstrate that the combined techniques of laser capture microdissection and multiplex-tandem PCR have the power to study molecular signaling within single cell populations derived from clinically sourced tissue. PMID:24475278

Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Kidney Effects

PubMed Central

Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Uehara, Takeki; Shymonyak, Svitlana; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

2014-01-01

Trichloroethylene (TCE) is a well-known environmental and occupational toxicant that is classified as carcinogenic to humans based on the epidemiological evidence of an association with higher risk of renal cell carcinoma. A number of scientific issues critical for assessing human health risks from TCE remain unresolved, such as the amount of kidney-toxic glutathione conjugation metabolites formed, inter-species and -individual differences, and the mode of action for kidney carcinogenicity. We hypothesized that TCE metabolite levels in the kidney are associated with kidney-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione], and various kidney toxicity phenotypes. In sub-acute study, we observed inter-strain differences in TCE metabolite levels in the kidney. In addition, we found that in several strains kidney-specific effects of TCE included induction of peroxisome proliferator-marker genes Cyp4a10 and Acox1, increased cell proliferation, and expression of KIM-1, a marker of tubular damage and regeneration. In sub-chronic study, peroxisome proliferator-marker gene induction and kidney toxicity diminished while cell proliferative response was elevated in a dose-dependent manner in NZW/LacJ, but not C57BL/6J mice. Overall, we show that TCE metabolite levels in the kidney are associated with kidney-specific toxicity and that these effects are strain-dependent. PMID:25424545

Volition and conflict in human medial frontal cortex

PubMed Central

Nachev, Parashkev; Rees, Geraint; Parton, Andrew; Kennard, Christopher; Husain, Masud

2009-01-01

Summary Controversy surrounds the role of human medial frontal cortex in controlling actions[1-5]. Although damage to this area leads to severe difficulties in spontaneously initiating actions[6], the precise mechanisms underlying such ‘volitional’ deficits remain to be established. Previous studies have implicated the medial frontal cortex in conflict monitoring[7-10] and the control of voluntary action[11, 12], suggesting that these key processes are functionally related or share neural substrates. Here we combine a novel behavioural paradigm with functional imaging of the oculomotor system to reveal for the first time a functional subdivision of the pre-supplementary motor area (pre-SMA) into anatomically distinct areas responding exclusively to volition or to conflict. We also demonstrate that activity in the supplementary eye field (SEF) distinguishes between success and failure in changing voluntary action plans during conflict, suggesting a role for the SEF in implementing the resolution of conflicting actions. We propose a functional architecture of human medial frontal cortex that incorporates the generation of action plans and the resolution of conflict. PMID:15668167

Separate encoding of model-based and model-free valuations in the human brain.

PubMed

Beierholm, Ulrik R; Anen, Cedric; Quartz, Steven; Bossaerts, Peter

2011-10-01

Behavioral studies have long shown that humans solve problems in two ways, one intuitive and fast (System 1, model-free), and the other reflective and slow (System 2, model-based). The neurobiological basis of dual process problem solving remains unknown due to challenges of separating activation in concurrent systems. We present a novel neuroeconomic task that predicts distinct subjective valuation and updating signals corresponding to these two systems. We found two concurrent value signals in human prefrontal cortex: a System 1 model-free reinforcement signal and a System 2 model-based Bayesian signal. We also found a System 1 updating signal in striatal areas and a System 2 updating signal in lateral prefrontal cortex. Further, signals in prefrontal cortex preceded choices that are optimal according to either updating principle, while signals in anterior cingulate cortex and globus pallidus preceded deviations from optimal choice for reinforcement learning. These deviations tended to occur when uncertainty regarding optimal values was highest, suggesting that disagreement between dual systems is mediated by uncertainty rather than conflict, confirming recent theoretical proposals. Copyright © 2011 Elsevier Inc. All rights reserved.

Unravelling the development of the visual cortex: implications for plasticity and repair

PubMed Central

Bourne, James A

2010-01-01

The visual cortex comprises over 50 areas in the human, each with a specified role and distinct physiology, connectivity and cellular morphology. How these individual areas emerge during development still remains something of a mystery and, although much attention has been paid to the initial stages of the development of the visual cortex, especially its lamination, very little is known about the mechanisms responsible for the arealization and functional organization of this region of the brain. In recent years we have started to discover that it is the interplay of intrinsic (molecular) and extrinsic (afferent connections) cues that are responsible for the maturation of individual areas, and that there is a spatiotemporal sequence in the maturation of the primary visual cortex (striate cortex, V1) and the multiple extrastriate/association areas. Studies in both humans and non-human primates have started to highlight the specific neural underpinnings responsible for the maturation of the visual cortex, and how experience-dependent plasticity and perturbations to the visual system can impact upon its normal development. Furthermore, damage to specific nuclei of the visual cortex, such as the primary visual cortex (V1), is a common occurrence as a result of a stroke, neurotrauma, disease or hypoxia in both neonates and adults alike. However, the consequences of a focal injury differ between the immature and adult brain, with the immature brain demonstrating a higher level of functional resilience. With better techniques for examining specific molecular and connectional changes, we are now starting to uncover the mechanisms responsible for the increased neural plasticity that leads to significant recovery following injury during this early phase of life. Further advances in our understanding of postnatal development/maturation and plasticity observed during early life could offer new strategies to improve outcomes by recapitulating aspects of the developmental program in the adult brain. PMID:20722872

Mutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice.

PubMed

De Tomasi, Lara; David, Pierre; Humbert, Camille; Silbermann, Flora; Arrondel, Christelle; Tores, Frédéric; Fouquet, Stéphane; Desgrange, Audrey; Niel, Olivier; Bole-Feysot, Christine; Nitschké, Patrick; Roume, Joëlle; Cordier, Marie-Pierre; Pietrement, Christine; Isidor, Bertrand; Khau Van Kien, Philippe; Gonzales, Marie; Saint-Frison, Marie-Hélène; Martinovic, Jelena; Novo, Robert; Piard, Juliette; Cabrol, Christelle; Verma, Ishwar C; Puri, Ratna; Journel, Hubert; Aziza, Jacqueline; Gavard, Laurent; Said-Menthon, Marie-Hélène; Heidet, Laurence; Saunier, Sophie; Jeanpierre, Cécile

2017-11-02

Congenital anomalies of the kidney and urinary tract (CAKUT) constitute a major cause of chronic kidney disease in children and 20% of prenatally detected anomalies. CAKUT encompass a spectrum of developmental kidney defects, including renal agenesis, hypoplasia, and cystic and non-cystic dysplasia. More than 50 genes have been reported as mutated in CAKUT-affected case subjects. However, the pathophysiological mechanisms leading to bilateral kidney agenesis (BKA) remain largely elusive. Whole-exome or targeted exome sequencing of 183 unrelated familial and/or severe CAKUT-affected case subjects, including 54 fetuses with BKA, led to the identification of 16 heterozygous variants in GREB1L (growth regulation by estrogen in breast cancer 1-like), a gene reported as a target of retinoic acid signaling. Four loss-of-function and 12 damaging missense variants, 14 being absent from GnomAD, were identified. Twelve of them were present in familial or simplex BKA-affected case subjects. Female BKA-affected fetuses also displayed uterus agenesis. We demonstrated a significant association between GREB1L variants and BKA. By in situ hybridization, we showed expression of Greb1l in the nephrogenic zone in developing mouse kidney. We generated a Greb1l knock-out mouse model by CRISPR-Cas9. Analysis at E13.5 revealed lack of kidneys and genital tract anomalies in male and female Greb1l -/- embryos and a slight decrease in ureteric bud branching in Greb1l +/- embryos. We showed that Greb1l invalidation in mIMCD3 cells affected tubulomorphogenesis in 3D-collagen culture, a phenotype rescued by expression of the wild-type human protein. This demonstrates that GREB1L plays a major role in early metanephros and genital development in mice and humans. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Growing kidney tissue from stem cells: how far from ‘party trick’ to medical application?

PubMed Central

Little, Melissa H

2016-01-01

The successful generation of kidney-like structures from human pluripotent stem cells, although slower to come than other tissue types, brings the hope of new therapies. While the demand for alternative treatments for kidney failure is acute, huge challenges remain to move these exciting but preliminary results towards clinical use. PMID:27257757

CMV induces HERV-K and HERV-W expression in kidney transplant recipients.

PubMed

Bergallo, Massimiliano; Galliano, Ilaria; Montanari, Paola; Gambarino, Stefano; Mareschi, Katia; Ferro, Francesca; Fagioli, Franca; Tovo, Pier-Angelo; Ravanini, Paolo

2015-07-01

Human endogenous retrovirus (HERVs) constitute approximately 8% of the human genome. Induction of HERV transcription is possible under certain circumstances, and may have a possible role in some pathological conditions. The aim of this study was to evaluate HERV-K and -W pol gene expression in kidney transplant recipients and to investigate the possible relationship between HERVs gene expression and CMV infection in these patients. Thirty-three samples of kidney transplant patients and twenty healthy blood donors were used to analyze, HERV-K and -W pol gene RNA expression by relative quantitative relative Real-Time PCR. We demonstrated that HERVs pol gene expression levels were higher in kidney transplant recipients than in healthy subjects. Moreover, HERV-K and -W pol gene expression was significantly higher in the group of kidney transplant recipients with high CMV viral load than in the groups with no or moderate CMV viral load. Our data suggest that CMV may facilitate in vivo HERV activation. Published by Elsevier B.V.

Quantitative Enzymatic and Immunologic Histophotometry of Diseased Human Kid-Ney Tissues Using Tv-Camera and Computer Assisted Image Processing Systems.

NASA Astrophysics Data System (ADS)

Heinert, G.; Mondorf, W.

1982-11-01

High speed image processing was used to analyse morphologic and metabolic characteristics of clinically relevant kidney tissue alterations.Qualitative computer-assisted histophotometry was performed to measure alterations in levels of the enzymes alkaline phosphatase (Ap),alanine aminopeptidase (AAP),g-glutamyltranspepti-dase (GGTP) and A-glucuronidase (B-G1) and AAP and GGTP immunologically determined in prepared renal and cancer tissue sections. A "Mioro-Videomat 2" image analysis system with a "Tessovar" macroscope,a computer-assisted "Axiomat" photomicroscope and an "Interactive Image Analysis System (IBAS)" were employed for analysing changes in enzyme activities determined by changes in absorbance or transmission.Diseased kidney as well as renal neoplastic tissues could be distinguished by significantly (wilcoxon test,p<0,05) decreased enzyme concentrations as compared to those found in normal human kidney tissues.This image analysis techniques might be of potential use in diagnostic and prognostic evaluation of renal cancer and diseased kidney tissues.

Conserved size and periodicity of pyramidal patches in layer 2 of medial/caudal entorhinal cortex

PubMed Central

Naumann, Robert K.; Ray, Saikat; Prokop, Stefan; Las, Liora; Heppner, Frank L.

2016-01-01

ABSTRACT To understand the structural basis of grid cell activity, we compare medial entorhinal cortex architecture in layer 2 across five mammalian species (Etruscan shrews, mice, rats, Egyptian fruit bats, and humans), bridging ∼100 million years of evolutionary diversity. Principal neurons in layer 2 are divided into two distinct cell types, pyramidal and stellate, based on morphology, immunoreactivity, and functional properties. We confirm the existence of patches of calbindin‐positive pyramidal cells across these species, arranged periodically according to analyses techniques like spatial autocorrelation, grid scores, and modifiable areal unit analysis. In rodents, which show sustained theta oscillations in entorhinal cortex, cholinergic innervation targeted calbindin patches. In bats and humans, which only show intermittent entorhinal theta activity, cholinergic innervation avoided calbindin patches. The organization of calbindin‐negative and calbindin‐positive cells showed marked differences in entorhinal subregions of the human brain. Layer 2 of the rodent medial and the human caudal entorhinal cortex were structurally similar in that in both species patches of calbindin‐positive pyramidal cells were superimposed on scattered stellate cells. The number of calbindin‐positive neurons in a patch increased from ∼80 in Etruscan shrews to ∼800 in humans, only an ∼10‐fold over a 20,000‐fold difference in brain size. The relatively constant size of calbindin patches differs from cortical modules such as barrels, which scale with brain size. Thus, selective pressure appears to conserve the distribution of stellate and pyramidal cells, periodic arrangement of calbindin patches, and relatively constant neuron number in calbindin patches in medial/caudal entorhinal cortex. J. Comp. Neurol. 524:783–806, 2016. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26223342

Conserved size and periodicity of pyramidal patches in layer 2 of medial/caudal entorhinal cortex.

PubMed

Naumann, Robert K; Ray, Saikat; Prokop, Stefan; Las, Liora; Heppner, Frank L; Brecht, Michael

2016-03-01

To understand the structural basis of grid cell activity, we compare medial entorhinal cortex architecture in layer 2 across five mammalian species (Etruscan shrews, mice, rats, Egyptian fruit bats, and humans), bridging ∼100 million years of evolutionary diversity. Principal neurons in layer 2 are divided into two distinct cell types, pyramidal and stellate, based on morphology, immunoreactivity, and functional properties. We confirm the existence of patches of calbindin-positive pyramidal cells across these species, arranged periodically according to analyses techniques like spatial autocorrelation, grid scores, and modifiable areal unit analysis. In rodents, which show sustained theta oscillations in entorhinal cortex, cholinergic innervation targeted calbindin patches. In bats and humans, which only show intermittent entorhinal theta activity, cholinergic innervation avoided calbindin patches. The organization of calbindin-negative and calbindin-positive cells showed marked differences in entorhinal subregions of the human brain. Layer 2 of the rodent medial and the human caudal entorhinal cortex were structurally similar in that in both species patches of calbindin-positive pyramidal cells were superimposed on scattered stellate cells. The number of calbindin-positive neurons in a patch increased from ∼80 in Etruscan shrews to ∼800 in humans, only an ∼10-fold over a 20,000-fold difference in brain size. The relatively constant size of calbindin patches differs from cortical modules such as barrels, which scale with brain size. Thus, selective pressure appears to conserve the distribution of stellate and pyramidal cells, periodic arrangement of calbindin patches, and relatively constant neuron number in calbindin patches in medial/caudal entorhinal cortex. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Modification of visual function by early visual experience.

PubMed

Blakemore, C

1976-07-01

Physiological experiments, involving recording from the visual cortex in young kittens and monkeys, have given new insight into human developmental disorders. In the visual cortex of normal cats and monkeys most neurones are selectively sensitive to the orientation of moving edges and they receive very similar signals from both eyes. Even in very young kittens without visual experience, most neurones are binocularly driven and a small proportion of them are genuinely orientation selective. There is no passive maturation of the system in the absence of visual experience, but even very brief exposure to patterned images produces rapid emergence of the adult organization. These results are compared to observations on humans who have "recovered" from early blindness. Covering one eye in a kitten or a monkey, during a sensitive period early in life, produces a virtually complete loss of input from that eye in the cortex. These results can be correlated with the production of "stimulus deprivation amblyopia" in infants who have had one eye patched. Induction of a strabismus causes a loss of binocularity in the visual cortex, and in humans it leads to a loss of stereoscopic vision and binocular fusion. Exposing kittens to lines of one orientation modifies the preferred orientations of cortical cells and there is an analogous "meridional amblyopia" in astigmatic humans. The existence of a sensitive period in human vision is discussed, as well as the possibility of designing remedial and preventive treatments for human developmental disorders.

The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans.

PubMed

Allman, John M; Tetreault, Nicole A; Hakeem, Atiya Y; Manaye, Kebreten F; Semendeferi, Katerina; Erwin, Joseph M; Park, Soyoung; Goubert, Virginie; Hof, Patrick R

2010-06-01

The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex in great apes and humans, but not other primates. We performed stereological counts of the VENs in FI and LA (limbic anterior, a component of anterior cingulate cortex) in great apes and in humans. The VENs are more numerous in humans than in apes, although one gorilla approached the lower end of the human range. We also examined the ontological development of the VENs in FI and LA in humans. The VENs first appear in small numbers in the 36th week post-conception, are rare at birth, and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than in the left in FI and LA in postnatal brains of apes and humans. This asymmetry in VEN numbers may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, which contains FI, is related to physiological changes in the body, decision-making, error recognition, and awareness. The VENs appear to be projection neurons, although their targets are unknown. We made a preliminary study of the connections of FI cortex based on diffusion tensor imaging in the brain of a gorilla. The VEN-containing regions connect to the frontal pole as well as to other parts of frontal and insular cortex, the septum, and the amygdala. It is likely that the VENs in FI are projecting to some or all of these structures and relaying information related to autonomic control, decision-making, or awareness. The VENs selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing peptide (GRP) which are also expressed in another population of closely related neurons, the fork cells. NMB and GRP signal satiety. The genes for NMB and GRP are expressed selectively in small populations of neurons in the insular cortex in mice. These populations may be related to the VEN and fork cells and may be involved in the regulation of appetite. The loss of these cells may be related to the loss of satiety signaling in patients with frontotemporal dementia who have damage to FI. The VENs and fork cells may be morphological specializations of an ancient population of neurons involved in the control of appetite present in the insular cortex in all mammals. We found that the protein encoded by the gene DISC1 (disrupted in schizophrenia) is preferentially expressed by the VENs. DISC1 has undergone rapid evolutionary change in the line leading to humans, and since it suppresses dendritic branching it may be involved in the distinctive VEN morphology.

Sox11 gene disruption causes congenital anomalies of the kidney and urinary tract (CAKUT).

PubMed

Neirijnck, Yasmine; Reginensi, Antoine; Renkema, Kirsten Y; Massa, Filippo; Kozlov, Vladimir M; Dhib, Haroun; Bongers, Ernie M H F; Feitz, Wout F; van Eerde, Albertien M; Lefebvre, Veronique; Knoers, Nine V A M; Tabatabaei, Mansoureh; Schulz, Herbert; McNeill, Helen; Schaefer, Franz; Wegner, Michael; Sock, Elisabeth; Schedl, Andreas

2018-05-01

Congenital abnormalities of the kidney and the urinary tract (CAKUT) belong to the most common birth defects in human, but the molecular basis for the majority of CAKUT patients remains unknown. Here we show that the transcription factor SOX11 is a crucial regulator of kidney development. SOX11 is expressed in both mesenchymal and epithelial components of the early kidney anlagen. Deletion of Sox11 in mice causes an extension of the domain expressing Gdnf within rostral regions of the nephrogenic cord and results in duplex kidney formation. On the molecular level SOX11 directly binds and regulates a locus control region of the protocadherin B cluster. At later stages of kidney development, SOX11 becomes restricted to the intermediate segment of the developing nephron where it is required for the elongation of Henle's loop. Finally, mutation analysis in a cohort of patients suffering from CAKUT identified a series of rare SOX11 variants, one of which interferes with the transactivation capacity of the SOX11 protein. Taken together these data demonstrate a key role for SOX11 in normal kidney development and may suggest that variants in this gene predispose to CAKUT in humans. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Heparin-based hydrogels induce human renal tubulogenesis in vitro.

PubMed

Weber, Heather M; Tsurkan, Mikhail V; Magno, Valentina; Freudenberg, Uwe; Werner, Carsten

2017-07-15

Dialysis or kidney transplantation is the only therapeutic option for end stage renal disease. Accordingly, there is a large unmet clinical need for new causative therapeutic treatments. Obtaining robust models that mimic the complex nature of the human kidney is a critical step in the development of new therapeutic strategies. Here we establish a synthetic in vitro human renal tubulogenesis model based on a tunable glycosaminoglycan-hydrogel platform. In this system, renal tubulogenesis can be modulated by the adjustment of hydrogel mechanics and degradability, growth factor signaling, and the presence of insoluble adhesion cues, potentially providing new insights for regenerative therapy. Different hydrogel properties were systematically investigated for their ability to regulate renal tubulogenesis. Hydrogels based on heparin and matrix metalloproteinase cleavable peptide linker units were found to induce the morphogenesis of single human proximal tubule epithelial cells into physiologically sized tubule structures. The generated tubules display polarization markers, extracellular matrix components, and organic anion transport functions of the in vivo renal proximal tubule and respond to nephrotoxins comparable to the human clinical response. The established hydrogel-based human renal tubulogenesis model is thus considered highly valuable for renal regenerative medicine and personalized nephrotoxicity studies. The only cure for end stage kidney disease is kidney transplantation. Hence, there is a huge need for reliable human kidney models to study renal regeneration and establish alternative treatments. Here we show the development and application of an in vitro human renal tubulogenesis model using heparin-based hydrogels. To the best of our knowledge, this is the first system where human renal tubulogenesis can be monitored from single cells to physiologically sized tubule structures in a tunable hydrogel system. To validate the efficacy of our model as a drug toxicity platform, a chemotherapy drug was incubated with the model, resulting in a drug response similar to human clinical pathology. The established model could have wide applications in the field of nephrotoxicity and renal regenerative medicine and offer a reliable alternative to animal models. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Identification of prefrontal cortex (BA10) activation while performing Stroop test using diffuse optical tomography

NASA Astrophysics Data System (ADS)

Khadka, Sabin; Chityala, Srujan R.; Tian, Fenghua; Liu, Hanli

2011-03-01

Stroop test is commonly used as a behavior-testing tool for psychological examinations that are related to attention and cognitive control of the human brain. Studies have shown activations in Broadmann area 10 (BA10) of prefrontal cortex (PFC) during attention and cognitive process. The use of diffuse optical tomography (DOT) for human brain mapping is becoming more prevalent. In this study we expect to find neural correlates between the performed cognitive tasks and hemodynamic signals detected by a DOT system. Our initial observation showed activation of oxy-hemoglobin concentration in BA 10, which is consistent with some results seen by positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Our study demonstrates the possibility of combining DOT with Stroop test to quantitatively investigate cognitive functions of the human brain at the prefrontal cortex.

Influence of mirror therapy on human motor cortex.

PubMed

Fukumura, Kenji; Sugawara, Kenichi; Tanabe, Shigeo; Ushiba, Junichi; Tomita, Yutaka

2007-07-01

This article investigates whether or not mirror therapy alters the neural mechanisms in human motor cortex. Six healthy volunteers participated. The study investigated the effects of three main factors of mirror therapy (observation of hand movements in a mirror, motor imagery of an assumed affected hand, and assistance in exercising the assumed affected hand) on excitability changes in the human motor cortex to clarify the contribution of each factor. The increase in motor-evoked potential (MEP) amplitudes during motor imagery tended to be larger with a mirror than without one. Moreover, MEP amplitudes increased greatly when movements were assisted. Watching the movement of one hand in a mirror makes it easier to move the other hand in the same way. Moreover, the increase in MEP amplitudes is related to the synergic effects of afferent information and motor imagery.

Targeting Iron Homeostasis in Acute Kidney Injury

PubMed Central

Walker, Vyvyca J.; Agarwal, Anupam

2017-01-01

Summary Iron is an essential metal involved in several major cellular processes required to maintain life. Because of iron’s ability to cause oxidative damage, its transport, metabolism, and storage is strictly controlled in the body, especially in the small intestine, liver, and kidney. Iron plays a major role in acute kidney injury and has been a target for therapeutic intervention. However, the therapies that have been effective in animal models of acute kidney injury have not been successful in human beings. Targeting iron trafficking via ferritin, ferroportin, or hepcidin may offer new insights. This review focuses on the biology of iron, particularly in the kidney, and its implications in acute kidney injury. PMID:27085736

Correlation of renal histopathology with renal echogenicity in dogs and cats: an ex-vivo quantitative study.

PubMed

Zotti, Alessandro; Banzato, Tommaso; Gelain, Maria Elena; Centelleghe, Cinzia; Vaccaro, Calogero; Aresu, Luca

2015-04-25

Increased cortical or cortical and medullary echogenicity is one of the most common signs of chronic or acute kidney disease in dogs and cats. Subjective evaluation of the echogenicity is reported to be unreliable. Patient and technical-related factors affect in-vivo quantitative evaluation of the echogenicity of parenchymal organs. The aim of the present study is to investigate the relationship between histopathology and ex-vivo renal cortical echogenicity in dogs and cats devoid of any patient and technical-related biases. Kidney samples were collected from 68 dog and 32 cat cadavers donated by the owners to the Veterinary Teaching Hospital of the University of Padua and standardized ultrasonographic images of each sample were collected. The echogenicity of the renal cortex was quantitatively assessed by means of mean gray value (MGV), and then histopathological analysis was performed. Statistical analysis to evaluate the influence of histological lesions on MGV was performed. The differentiation efficiency of MGV to detect pathological changes in the kidneys was calculated for dogs and cats. Statistical analysis revealed that only glomerulosclerosis was an independent determinant of echogenicity in dogs whereas interstitial nephritis, interstitial necrosis and fibrosis were independent determinants of echogenicity in cats. The global influence of histological lesions on renal echogenicity was higher in cats (23%) than in dogs (12%). Different histopathological lesions influence the echogenicity of the kidneys in dogs and cats. Moreover, MGV is a poor test for distinguishing between normal and pathological kidneys in the dog with a sensitivity of 58.3% and specificity of 59.8%. Instead, it seems to perform globally better in the cat, resulting in a fair test, with a sensitivity of 80.6% and a specificity of 56%.

Mass spectrometric imaging of metabolites in kidney tissues from rats treated with furosemide.

PubMed

Jung, Jin Woo; Lee, Mi Suk; Choi, Hyo-Jung; Jung, Sunhee; Lee, Yu-Jung; Hwang, Geum-Sook; Kwon, Tae-Hwan

2016-06-01

In the kidney, metabolic processes are different among the cortex (COR), outer medulla (OM), and inner medulla (IM). Using matrix-assisted laser desorption/ionization (MALDI) and imaging mass spectrometry (IMS), we examined the change of metabolites in the COR, OM, and IM of the rat kidney after furosemide treatment compared with vehicle-treated controls. Osmotic minipumps were implanted in male Sprague-Dawley rats to deliver 12 mg·day(-1)·rat(-1) of furosemide. Vehicle-treated (n = 14) and furosemide-treated (furosemide rats, n = 15) rats in metabolic cages received a fixed amount of rat chow (15 g·220 g body wt(-1)·day(-1) for each rat) with free access to water intake for 6 days. At day 6, higher urine output (32 ± 4 vs. 9 ± 1 ml/day) and lower urine osmolality (546 ± 44 vs. 1,677 ± 104 mosmol/kgH2O) were observed in furosemide rats. Extracts of COR, OM, and IM were analyzed by ultraperformance liquid chromatography coupled with quadrupole time-of-flight (TOF) mass spectrometry, where multivariate analysis revealed significant differences between the two groups. Several metabolites, including acetylcarnitine, betaine, carnitine, choline, and glycerophosphorylcholine (GPC), were significantly changed. The changes of metabolites were further identified by MALDI-TOF/TOF and IMS. Their spatial distribution and relative quantitation in the kidneys were analyzed by IMS. Carnitine compounds were increased in COR and IM, whereas carnitine and acetylcarnitine were decreased in OM. Choline compounds were increased in COR and OM but decreased in IM from furosemide rats. Betaine and GPC were decreased in OM and IM. Taken together, MALDI-TOF/TOF and IMS successfully provide the spatial distribution and relative quantitation of metabolites in the kidney. Copyright © 2016 the American Physiological Society.

Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

PubMed Central

Caires, A.; Fernandes, G.S.; Leme, A.M.; Castino, B.; Pessoa, E.A.; Fernandes, S.M.; Fonseca, C.D.; Vattimo, M.F.; Schor, N.; Borges, F.T.

2017-01-01

Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects. PMID:29267497

Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats.

PubMed

Caires, A; Fernandes, G S; Leme, A M; Castino, B; Pessoa, E A; Fernandes, S M; Fonseca, C D; Vattimo, M F; Schor, N; Borges, F T

2017-12-11

Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

Acute Knockdown of Uncoupling Protein-2 Increases Uncoupling via the Adenine Nucleotide Transporter and Decreases Oxidative Stress in Diabetic Kidneys

PubMed Central

Friederich-Persson, Malou; Aslam, Shakil; Nordquist, Lina; Welch, William J.; Wilcox, Christopher S.; Palm, Fredrik

2012-01-01

Increased O2 metabolism resulting in chronic hypoxia is common in models of endstage renal disease. Mitochondrial uncoupling increases O2 consumption but the ensuing reduction in mitochondrial membrane potential may limit excessive oxidative stress. The present study addressed the hypothesis that mitochondrial uncoupling regulates mitochondria function and oxidative stress in the diabetic kidney. Isolated mitochondria from kidney cortex of control and streptozotocin-induced diabetic rats were studied before and after siRNA knockdown of uncoupling protein-2 (UCP-2). Diabetes resulted in increased UCP-2 protein expression and UCP-2-mediated uncoupling, but normal mitochondria membrane potential. This uncoupling was inhibited by GDP, which also increased the membrane potential. siRNA reduced UCP-2 protein expression in controls and diabetics (−30–50%), but paradoxically further increased uncoupling and markedly reduced the membrane potential. This siRNA mediated uncoupling was unaffected by GDP but was blocked by ADP and carboxyatractylate (CAT). Mitochondria membrane potential after UCP-2 siRNA was unaffected by GDP but increased by CAT. This demonstrated that further increased mitochondria uncoupling after siRNA towards UCP-2 is mediated through the adenine nucleotide transporter (ANT). The increased oxidative stress in the diabetic kidney, manifested as increased thiobarbituric acids, was reduced by knocking down UCP-2 whereas whole-body oxidative stress, manifested as increased circulating malondialdehyde, remained unaffected. All parameters investigated were unaffected by scrambled siRNA. In conclusion, mitochondrial uncoupling via UCP-2 regulates mitochondria membrane potential in diabetes. However, blockade of the diabetes-induced upregulation of UCP- 2 results in excessive uncoupling and reduced oxidative stress in the kidney via activation of ANT. PMID:22768304

Investigation of aquaporins and apparent diffusion coefficient from ultra-high b-values in a rat model of diabetic nephropathy.

PubMed

Wang, Yu; Zhang, Heng; Zhang, Ruzhi; Zhao, Zhoushe; Xu, Ziqian; Wang, Lei; Liu, Rongbo; Gao, Fabao

2017-01-01

To assess kidney damage in a rat model of type-2 diabetic nephropathy based on apparent diffusion coefficient (ADC) data obtained from ultra-high b-values and discuss its relationship to the expression of aquaporins (AQPs). This study was approved by the institutional Animal Care and Use Committee. Thirty male Sprague-Dawley rats were randomised into two groups: (1) untreated controls and (2) diabetes mellitus (DM). All rats underwent diffusion-weighted imaging (DWI) with 18 b-values (0-4500 s/mm 2 ). Maps of low ADC (ADC low ), standard ADC (ADC st ) and ultra-high ADC (ADC uh ) were calculated from low b-values (0-200 s/mm 2 ), standard b-values (300-1500 s/mm 2 ) and ultra-high b-values (1700-4500 s/mm 2 ), respectively. The expression of AQPs in the kidneys was studied using immunohistochemistry. Laboratory parameters of diabetic and kidney functions, ADC low , ADC st , ADC uh , and the optical density (OD) of AQP expression in the two groups were compared using an independent t test. Correlations between ADCs and the OD of AQP expression were evaluated by Pearson's correlation analysis. ADC uh were significantly higher in the cortex (CO), outer stripe of the outer medulla (OS) and inner stripe of the outer medulla (IS), and the OD values of AQ-2 were significantly higher in the OS, IS and inner medulla (IM) in DM animals compared with control animals. ADC uh and OD values of AQP-2 expression were positively correlated in the OS, IS and IM of the kidney. ADC uh may work as useful metrics for early detection of kidney damage in diabetic nephropathy and may be associated with AQP-2 expression.

Aging Selectively Modulates Vitamin C Transporter Expression Patterns in the Kidney.

PubMed

Forman, Katherine; Martínez, Fernando; Cifuentes, Manuel; Bertinat, Romina; Salazar, Katterine; Nualart, Francisco

2017-09-01

In the kidney, vitamin C is reabsorbed from the glomerular ultrafiltrate by sodium-vitamin C cotransporter isoform 1 (SVCT1) located in the brush border membrane of the proximal tubules. Although we know that vitamin C levels decrease with age, the adaptive physiological mechanisms used by the kidney for vitamin C reabsorption during aging remain unknown. In this study, we used an animal model of accelerated senescence (SAMP8 mice) to define the morphological alterations and aging-induced changes in the expression of vitamin C transporters in renal tissue. Aging induced significant morphological changes, such as periglomerular lymphocytic infiltrate and glomerular congestion, in the kidneys of SAMP8 mice, although no increase in collagen deposits was observed using 2-photon microscopy analysis and second harmonic generation. The most characteristic histological alteration was the dilation of intracellular spaces in the basolateral region of proximal tubule epithelial cells. Furthermore, a combination of laser microdissection, qRT-PCR, and immunohistochemical analyses allowed us to determine that SVCT1 expression specifically increased in the proximal tubules from the outer strip of the outer medulla (segment S3) and cortex (segment S2) during aging and that these tubules also express GLUT1. We conclude that aging modulates vitamin C transporter expression and that renal over-expression of SVCT1 enhances vitamin C reabsorption in aged animals that may synthesize less vitamin C. J. Cell. Physiol. 232: 2418-2426, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway.

PubMed

Lv, Xing; Lv, Gao-Hong; Dai, Guo-Ying; Sun, Hong-Mei; Xu, Hui-Qin

2016-11-01

The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein (CRP), low density lipoprotein (LDL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species (ROS) and low-levels of superoxide dismutase (SOD) in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Four-dimensional MRI of renal function in the developing mouse.

PubMed

Xie, Luke; Subashi, Ergys; Qi, Yi; Knepper, Mark A; Johnson, G Allan

2014-09-01

The major roles of filtration, metabolism and high blood flow make the kidney highly vulnerable to drug-induced toxicity and other renal injuries. A method to follow kidney function is essential for the early screening of toxicity and malformations. In this study, we acquired high spatiotemporal resolution (four dimensional) datasets of normal mice to follow changes in kidney structure and function during development. The data were acquired with dynamic contrast-enhanced MRI (via keyhole imaging) and a cryogenic surface coil, allowing us to obtain a full three-dimensional image (isotropic resolution, 125 microns) every 7.7 s over a 50-min scan. This time course permitted the demonstration of both contrast enhancement and clearance. Functional changes were measured over a 17-week course (at 3, 5, 7, 9, 13 and 17 weeks). The time dimension of the MRI dataset was processed to produce unique image contrasts to segment the four regions of the kidney: cortex (CO), outer stripe (OS) of the outer medulla (OM), inner stripe (IS) of the OM and inner medulla (IM). Local volumes, time-to-peak (TTP) values and decay constants (DC) were measured in each renal region. These metrics increased significantly with age, with the exception of DC values in the IS and OS. These data will serve as a foundation for studies of normal renal physiology and future studies of renal diseases that require early detection and intervention. Copyright © 2014 John Wiley & Sons, Ltd.

Prospective MR image alignment between breath-holds: Application to renal BOLD MRI.

PubMed

Kalis, Inge M; Pilutti, David; Krafft, Axel J; Hennig, Jürgen; Bock, Michael

2017-04-01

To present an image registration method for renal blood oxygen level-dependent (BOLD) measurements that enables semiautomatic assessment of parenchymal and medullary R2* changes under a functional challenge. In a series of breath-hold acquisitions, three-dimensional data were acquired initially for prospective image registration of subsequent BOLD measurements. An algorithm for kidney alignment for BOLD renal imaging (KALIBRI) was implemented to detect the positions of the left and right kidney so that the kidneys were acquired in the subsequent BOLD measurement at consistent anatomical locations. Residual in-plane distortions were corrected retrospectively so that semiautomatic dynamic R2* measurements of the renal cortex and medulla become feasible. KALIBRI was tested in six healthy volunteers during a series of BOLD experiments, which included a 600- to 1000-mL water challenge. Prospective image registration and BOLD imaging of each kidney was achieved within a total measurement time of about 17 s, enabling its execution within a single breath-hold. KALIBRI improved the registration by up to 35% as found with mutual information measures. In four volunteers, a medullary R2* decrease of up to 40% was observed after water ingestion. KALIBRI improves the quality of two-dimensional time-resolved renal BOLD MRI by aligning local renal anatomy, which allows for consistent R2* measurements over many breath-holds. Magn Reson Med 77:1573-1582, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Effect of passage number on electrophoretic mobility distributions of cultured human embryonic kidney cells

NASA Technical Reports Server (NTRS)

Kunze, M. E.

1985-01-01

A systematic investigation was undertaken to characterize population shifts that occur in cultured human embryonic kidney cells as a function of passage number in vitro after original explantation. This approach to cell population shift analysis follows the suggestion of Mehreshi, Klein and Revesz that perturbed cell populations can be characterized by electrophoretic mobility distributions if they contain subpopulations with different electrophoretic mobilities. It was shown that this is the case with early passage cultured human embryo cells.

Lateralized Contribution of Prefrontal Cortex in Controlling Task-Irrelevant Information during Verbal and Spatial Working Memory Tasks: rTMS Evidence

ERIC Educational Resources Information Center

Sandrini, Marco; Rossini, Paolo Maria; Miniussi, Carlo

2008-01-01

The functional organization of working memory (WM) in the human prefrontal cortex remains unclear. The present study used repetitive transcranial magnetic stimulation (rTMS) to clarify the role of the dorsolateral prefrontal cortex (dlPFC) both in the types of information (verbal vs. spatial), and the types of processes (maintenance vs.…

Comparison of In Vitro- and Chorioallantoic Membrane (CAM)-Culture Systems for Cryopreserved Medulla-Contained Human Ovarian Tissue

PubMed Central

Isachenko, Vladimir; Mallmann, Peter; Petrunkina, Anna M.; Rahimi, Gohar; Nawroth, Frank; Hancke, Katharina; Felberbaum, Ricardo; Genze, Felicitas; Damjanoski, Ilija; Isachenko, Evgenia

2012-01-01

At present, there are three ways to determine effectively the quality of the cryopreservation procedure using ovarian tissue before the re-implantation treatment: evaluation of follicles after post-thawing xenotransplantation to SCID mouse, in-vitro culture in a large volume of culture medium under constant agitation and culture on embryonic chorio-allantoic membrane within a hen's eggs. The aim of this study was to compare the two methods, culture in vitro and culture on embryonic chorioallantoic membrane (CAM) of cryopreserved human ovarian medulla-contained and medulla-free cortex. Ovarian fragments were divided into small pieces (1.5–2.0×1.0–1.2×0.8–1.5) of two types, cortex with medulla and medulla-free cortex, frozen, thawed and randomly divided into the following four groups. Group 1: medulla-free cortex cultured in vitro for 8 days in large volume of medium with mechanical agitation, Group 2: medulla-containing cortex cultured in vitro, Group 3: medulla-free cortex cultured in CAM-system for 5 days, Group 4: medulla-containing cortex cultured in CAM-system. The efficacy of the tissue culture was evaluated by the development of follicles and by intensiveness of angiogenesis in the tissue (von Willebrand factor and Desmin). For Group 1, 2, 3 and 4, respectively 85%, 85%, 87% and 84% of the follicles were morphologically normal (P>0.1). The immunohistochemical analysis showed that angiogenesis detected by von Willebrand factor was lower in groups 1 and 3 (medulla-free cortex). Neo-vascularisation (by Desmin) was observed only in ovarian tissue of Group 4 (medulla-contained cortex after CAM-culture). It appears that the presence of medulla in ovarian pieces is beneficial for post-thaw development of cryopreserved human ovarian tissue. For medical practice it is recommended for evaluation of post-warming ovarian tissue to use the CAM-system as a valuable alternative to xenotransplantation and for cryopreservation of these tissues to prepare ovarian medulla-contained strips. PMID:22479331

Saturation in Phosphene Size with Increasing Current Levels Delivered to Human Visual Cortex.

PubMed

Bosking, William H; Sun, Ping; Ozker, Muge; Pei, Xiaomei; Foster, Brett L; Beauchamp, Michael S; Yoshor, Daniel

2017-07-26

Electrically stimulating early visual cortex results in a visual percept known as a phosphene. Although phosphenes can be evoked by a wide range of electrode sizes and current amplitudes, they are invariably described as small. To better understand this observation, we electrically stimulated 93 electrodes implanted in the visual cortex of 13 human subjects who reported phosphene size while stimulation current was varied. Phosphene size increased as the stimulation current was initially raised above threshold, but then rapidly reached saturation. Phosphene size also depended on the location of the stimulated site, with size increasing with distance from the foveal representation. We developed a model relating phosphene size to the amount of activated cortex and its location within the retinotopic map. First, a sigmoidal curve was used to predict the amount of activated cortex at a given current. Second, the amount of active cortex was converted to degrees of visual angle by multiplying by the inverse cortical magnification factor for that retinotopic location. This simple model accurately predicted phosphene size for a broad range of stimulation currents and cortical locations. The unexpected saturation in phosphene sizes suggests that the functional architecture of cerebral cortex may impose fundamental restrictions on the spread of artificially evoked activity and this may be an important consideration in the design of cortical prosthetic devices. SIGNIFICANCE STATEMENT Understanding the neural basis for phosphenes, the visual percepts created by electrical stimulation of visual cortex, is fundamental to the development of a visual cortical prosthetic. Our experiments in human subjects implanted with electrodes over visual cortex show that it is the activity of a large population of cells spread out across several millimeters of tissue that supports the perception of a phosphene. In addition, we describe an important feature of the production of phosphenes by electrical stimulation: phosphene size saturates at a relatively low current level. This finding implies that, with current methods, visual prosthetics will have a limited dynamic range available to control the production of spatial forms and that more advanced stimulation methods may be required. Copyright © 2017 the authors 0270-6474/17/377188-10$15.00/0.

Dynamic Increase in Corticomuscular Coherence during Bilateral, Cyclical Ankle Movements

PubMed Central

Yoshida, Takashi; Masani, Kei; Zabjek, Karl; Chen, Robert; Popovic, Milos R.

2017-01-01

In humans, the midline primary motor cortex is active during walking. However, the exact role of such cortical participation is unknown. To delineate the role of the primary motor cortex in walking, we examined whether the primary motor cortex would activate leg muscles during movements that retained specific requirements of walking (i.e., locomotive actions). We recorded electroencephalographic and electromyographic signals from 15 healthy, young men while they sat and performed bilateral, cyclical ankle movements. During dorsiflexion, near-20-Hz coherence increased cyclically between the midline primary motor cortex and the co-contracting antagonistic pair (i.e., tibialis anterior and medial gastrocnemius muscles) in both legs. Thus, we have shown that dynamic increase in corticomuscular coherence, which has been observed during walking, also occurs during simple bilateral cyclical movements of the feet. A possible mechanism for such coherence is corticomuscular communication, in which the primary motor cortex participates in the control of movement. Furthermore, because our experimental task isolated certain locomotive actions, the observed coherence suggests that the human primary motor cortex may participate in these actions (i.e., maintaining a specified movement frequency, bilaterally coordinating the feet, and stabilizing the posture of the feet). Additional studies are needed to identify the exact cortical and subcortical interactions that cause corticomuscular coherence and to further delineate the functional role of the primary motor cortex during bilateral cyclical movements such as walking. PMID:28420971

Evidence for pitch chroma mapping in human auditory cortex.

PubMed

Briley, Paul M; Breakey, Charlotte; Krumbholz, Katrin

2013-11-01

Some areas in auditory cortex respond preferentially to sounds that elicit pitch, such as musical sounds or voiced speech. This study used human electroencephalography (EEG) with an adaptation paradigm to investigate how pitch is represented within these areas and, in particular, whether the representation reflects the physical or perceptual dimensions of pitch. Physically, pitch corresponds to a single monotonic dimension: the repetition rate of the stimulus waveform. Perceptually, however, pitch has to be described with 2 dimensions, a monotonic, "pitch height," and a cyclical, "pitch chroma," dimension, to account for the similarity of the cycle of notes (c, d, e, etc.) across different octaves. The EEG adaptation effect mirrored the cyclicality of the pitch chroma dimension, suggesting that auditory cortex contains a representation of pitch chroma. Source analysis indicated that the centroid of this pitch chroma representation lies somewhat anterior and lateral to primary auditory cortex.

Evidence for Pitch Chroma Mapping in Human Auditory Cortex

PubMed Central

Briley, Paul M.; Breakey, Charlotte; Krumbholz, Katrin

2013-01-01

Some areas in auditory cortex respond preferentially to sounds that elicit pitch, such as musical sounds or voiced speech. This study used human electroencephalography (EEG) with an adaptation paradigm to investigate how pitch is represented within these areas and, in particular, whether the representation reflects the physical or perceptual dimensions of pitch. Physically, pitch corresponds to a single monotonic dimension: the repetition rate of the stimulus waveform. Perceptually, however, pitch has to be described with 2 dimensions, a monotonic, “pitch height,” and a cyclical, “pitch chroma,” dimension, to account for the similarity of the cycle of notes (c, d, e, etc.) across different octaves. The EEG adaptation effect mirrored the cyclicality of the pitch chroma dimension, suggesting that auditory cortex contains a representation of pitch chroma. Source analysis indicated that the centroid of this pitch chroma representation lies somewhat anterior and lateral to primary auditory cortex. PMID:22918980

Oscillations in human orbitofrontal cortex during even chance gambling.

PubMed

Kahn, Kevin; Kerr, Matthew S D; Park, Hyun-Joo; Thompson, Susan; Bulacio, Juan; Gonzalez-Martinez, Jorge; Sarma, Sridevi V; Gale, John

2014-01-01

Evaluating value and risk as well as comparing expected and actual outcomes is the crux of decision making and reinforcement based learning. In this study, we record from stereotactic electroencephalograph depth electrodes in a human subject in numerous areas in the brain. We focus on the lateral and medial orbitofrontal cortex while they perform a gambling task involving betting on a high card. Preliminary time-frequency analysis shows modulations in the 5-15 Hz band that is well synced to the different events of the task. These oscillations increase in both high betting scenarios as well as in losing scenarios though their effects cannot be decoupled. However, the activity between lateral and medial orbitofrontal cortex is a lot more homogenous than previously seen. Additionally, the timing of some of these oscillations occurs before even a response in the visual cortex. This evidence hints that these areas encode priors that influence our decision in future statistically ambiguous scenarios.

Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain

PubMed Central

Liang, Winnie S.; Dunckley, Travis; Beach, Thomas G.; Grover, Andrew; Mastroeni, Diego; Walker, Douglas G.; Caselli, Richard J.; Kukull, Walter A.; McKeel, Daniel; Morris, John C.; Hulette, Christine; Schmechel, Donald; Alexander, Gene E.; Reiman, Eric M.; Rogers, Joseph; Stephan, Dietrich A.

2008-01-01

In this article, we have characterized and compared gene expression profiles from laser capture microdissected neurons in six functionally and anatomically distinct regions from clinically and histopathologically normal aged human brains. These regions, which are also known to be differentially vulnerable to the histopathological and metabolic features of Alzheimer’s disease (AD), include the entorhinal cortex and hippocampus (limbic and paralimbic areas vulnerable to early neurofibrillary tangle pathology in AD), posterior cingulate cortex (a paralimbic area vulnerable to early metabolic abnormalities in AD), temporal and prefrontal cortex (unimodal and heteromodal sensory association areas vulnerable to early neuritic plaque pathology in AD), and primary visual cortex (a primary sensory area relatively spared in early AD). These neuronal profiles will provide valuable reference information for future studies of the brain, in normal aging, AD and other neurological and psychiatric disorders. PMID:17077275

Magnetic Field Homogenization of the Human Prefrontal Cortex with a Set of Localized Electrical Coils

PubMed Central

Juchem, Christoph; Nixon, Terence W.; McIntyre, Scott; Rothman, Douglas L.; de Graaf, Robin A.

2011-01-01

The prefrontal cortex is a common target brain structure in psychiatry and neuroscience due to its role in working memory and cognitive control. Large differences in magnetic susceptibility between the air-filled sinuses and the tissue/bone in the frontal part of the human head cause a strong and highly localized magnetic field focus in the prefrontal cortex. As a result, image distortion and signal dropout are observed in MR imaging. A set of external, electrical coils is presented that provides localized and high amplitude shim fields in the prefrontal cortex with minimum impact on the rest of the brain when combined with regular zero-to-second order spherical harmonics shimming. The experimental realization of the new shim method strongly minimized or even eliminated signal dropout in gradient-echo images acquired at settings typically used in functional magnetic resonance at 4 Tesla. PMID:19918909

Pathology Report for One-Generation Study of the Effects of 3-nitro-1,2,4-triazol-5-one (NTO) to the Northern Leopard Frog (lithobates pipiens) Under Static Renewal Test Conditions

DTIC Science & Technology

2015-12-28

Figures 1 20C1 High-dose Frog, Kidney ............................................................................... 5 2 00A1 Control, Kidney ...controls to 60+ days PH in the high NTO concentration. Froglets were humanely euthanized using MS-222 and liver and kidney tissues dissected, fixed...and cover-slipped. 4 Individual Animal Descriptions  00A1 Kidney (Control): Disrupting approximately 20% of the renal parenchyma (tubules and

Hemispherical map for the human brain cortex

NASA Astrophysics Data System (ADS)

Tosun, Duygu; Prince, Jerry L.

2001-07-01

Understanding the function of the human brain cortex is a primary goal in human brain mapping. Methods to unfold and flatten the cortical surface for visualization and measurement have been described in previous literature; but comparison across multiple subjects is still difficult because of the lack of a standard mapping technique. We describe a new approach that maps each hemisphere of the cortex to a portion of a sphere in a standard way, making comparison of anatomy and function across different subjects possible. Starting with a three-dimensional magnetic resonance image of the brain, the cortex is segmented and represented as a triangle mesh. Defining a cut around the corpus collosum identifies the left and right hemispheres. Together, the two hemispheres are mapped to the complex plane using a conformal mapping technique. A Mobius transformation, which is conformal, is used to transform the points on the complex plane so that a projective transformation maps each brain hemisphere onto a spherical segment comprising a sphere with a cap removed. We determined the best size of the spherical cap by minimizing the relative area distortion between hemispherical maps and original cortical surfaces. The relative area distortion between the hemispherical maps and the original cortical surfaces for fifteen human brains is analyzed.

Interpreting sulci on hominin endocasts: old hypotheses and new findings

PubMed Central

Falk, Dean

2014-01-01

Paleoneurologists analyze internal casts (endocasts) of fossilized braincases, which provide information about the size, shape and, to a limited degree, sulcal patterns reproduced from impressions left by the surface of the brain. When interpreted in light of comparative data from the brains of living apes and humans, sulcal patterns reproduced on hominin endocasts provide important information for studying the evolution of the cerebral cortex and cognition in human ancestors. Here, new evidence is discussed for the evolution of sulcal patterns associated with cortical reorganization in three parts of the hominin brain: (1) the parietotemporo-occipital association cortex, (2) Broca's speech area, and (3) dorsolateral prefrontal association cortex. Of the three regions, the evidence regarding the last is the clearest. Compared to great apes, Australopithecus endocasts reproduce a clear middle frontal sulcus in the dorsolateral prefrontal cortex that is derived toward the human condition. This finding is consistent with data from comparative cytoarchitectural studies of ape and human brains as well as shape analyses of australopithecine endocasts. The comparative and direct evidence for all three regions suggests that hominin brain reorganization was underway by at least the time of Australopithecus africanus (~2.5 to 3.0 mya), despite the ape-sized brains of these hominins, and that it entailed expansion of both rostral and caudal association cortices. PMID:24822043

Human kidney proximal tubule cells are vulnerable to the effects of Rauwolfia serpentina.

PubMed

Mossoba, Miriam E; Flynn, Thomas J; Vohra, Sanah; Wiesenfeld, Paddy L; Sprando, Robert L

2015-12-01

Rauwolfia serpentina (or Snake root plant) is a botanical dietary supplement marketed in the USA for maintaining blood pressure. Very few studies have addressed the safety of this herb, despite its wide availability to consumers. Its reported pleiotropic effects underscore the necessity for evaluating its safety. We used a human kidney cell line to investigate the possible negative effects of R. serpentina on the renal system in vitro, with a specific focus on the renal proximal tubules. We evaluated cellular and mitochondrial toxicity, along with a variety of other kidney-specific toxicology biomarkers. We found that R. serpentina was capable of producing highly detrimental effects in our in vitro renal cell system. These results suggest more studies are needed to investigate the safety of this dietary supplement in both kidney and other target organ systems.

The directed differentiation of human iPS cells into kidney podocytes.

PubMed

Song, Bi; Smink, Alexandra M; Jones, Christina V; Callaghan, Judy M; Firth, Stephen D; Bernard, Claude A; Laslett, Andrew L; Kerr, Peter G; Ricardo, Sharon D

2012-01-01

The loss of glomerular podocytes is a key event in the progression of chronic kidney disease resulting in proteinuria and declining function. Podocytes are slow cycling cells that are considered terminally differentiated. Here we provide the first report of the directed differentiation of induced pluripotent stem (iPS) cells to generate kidney cells with podocyte features. The iPS-derived podocytes share a morphological phenotype analogous with cultured human podocytes. Following 10 days of directed differentiation, iPS podocytes had an up-regulated expression of mRNA and protein localization for podocyte markers including synaptopodin, nephrin and Wilm's tumour protein (WT1), combined with a down-regulation of the stem cell marker OCT3/4. In contrast to human podocytes that become quiescent in culture, iPS-derived cells maintain a proliferative capacity suggestive of a more immature phenotype. The transduction of iPS podocytes with fluorescent labeled-talin that were immunostained with podocin showed a cytoplasmic contractile response to angiotensin II (AII). A permeability assay provided functional evidence of albumin uptake in the cytoplasm of iPS podocytes comparable to human podocytes. Moreover, labeled iPS-derived podocytes were found to integrate into reaggregated metanephric kidney explants where they incorporated into developing glomeruli and co-expressed WT1. This study establishes the differentiation of iPS cells to kidney podocytes that will be useful for screening new treatments, understanding podocyte pathogenesis, and offering possibilities for regenerative medicine.

Human kidney methoxyflurane and sevoflurane metabolism. Intrarenal fluoride production as a possible mechanism of methoxyflurane nephrotoxicity.

PubMed

Kharasch, E D; Hankins, D C; Thummel, K E

1995-03-01

Methoxyflurane nephrotoxicity is mediated by cytochrome P450-catalyzed metabolism to toxic metabolites. It is historically accepted that one of the metabolites, fluoride, is the nephrotoxin, and that methoxyflurane nephrotoxicity is caused by plasma fluoride concentrations in excess of 50 microM. Sevoflurane also is metabolized to fluoride ion, and plasma concentrations may exceed 50 microM, yet sevoflurane nephrotoxicity has not been observed. It is possible that in situ renal metabolism of methoxyflurane, rather than hepatic metabolism, is a critical event leading to nephrotoxicity. We tested whether there was a metabolic basis for this hypothesis by examining the relative rates of methoxyflurane and sevoflurane defluorination by human kidney microsomes. Microsomes and cytosol were prepared from kidneys of organ donors. Methoxyflurane and sevoflurane metabolism were measured with a fluoride-selective electrode. Human cytochrome P450 isoforms contributing to renal anesthetic metabolism were identified by using isoform-selective inhibitors and by Western blot analysis of renal P450s in conjunction with metabolism by individual P450s expressed from a human hepatic complementary deoxyribonucleic acid library. Sevoflurane and methoxyflurane did undergo defluorination by human kidney microsomes. Fluoride production was dependent on time, reduced nicotinamide adenine dinucleotide phosphate, protein concentration, and anesthetic concentration. In seven human kidneys studied, enzymatic sevoflurane defluorination was minima, whereas methoxyflurane defluorination rates were substantially greater and exhibited large interindividual variability. Kidney cytosol did not catalyze anesthetic defluorination. Chemical inhibitors of the P450 isoforms 2E1, 2A6, and 3A diminished methoxyflurane and sevoflurane defluorination. Complementary deoxyribonucleic acid-expressed P450s 2E1, 2A6, and 3A4 catalyzed methoxyflurane and sevoflurane metabolism, in diminishing order of activity. These three P450s catalyzed the defluorination of methoxyflurane three to ten times faster than they did that of sevoflurane. Expressed P450 2B6 also catalyzed methoxyflurane defluorination, but 2B6 appeared not to contribute to renal microsomal methoxyflurane defluorination because the P450 2B6-selective inhibitor had no effect. Human kidney microsomes metabolize methoxyflurane, and to a much lesser extent sevoflurane, to fluoride ion. P450s 2E1 and/or 2A6 and P450 3A are implicated in the defluorination. If intrarenally generated fluoride or other metabolites are nephrotoxic, then renal metabolism may contribute to methoxyflurane nephrotoxicity. The relative paucity of renal sevoflurane defluorination may explain the absence of clinical sevoflurane nephrotoxicity to date, despite plasma fluoride concentrations that may exceed 50 microM.

Groundwater chemistry and human health risk assessment in the mining region of East Singhbhum, Jharkhand, India.

PubMed

Singh, Umesh Kumar; Ramanathan, A L; Subramanian, V

2018-08-01

Groundwater chemistry of mining region of East Singhbhum district having complex contaminant sources were investigated based on heavy metals loads and other hydrochemical constituents. This study aimed to identify the degree of heavy metals exposure and their potential health risk to local population. The results of hydrochemical analysis showed that Na + , K + , and Ca 2+ ions are the dominant cations in the groundwater, while HCO 3 - , F - and Cl - ions dominate the anionic part of the groundwater. The weathering process was considered the dominant factor to determine the major ionic composition in the study area. Compositional analysis for heavy metal has identified that groundwater of the study area is contaminated by Cd, Pb and Cr elements. Source of these metals have been identified as an anthropogenic inputs from mining activities and mineral processing units. Health risk analysis of individual heavy metal for chronic daily intake (CDI) and hazard quotient (HQ) was found in the order of Cr > As > Cd > Pb which is indicating high health risk for the population. In addition, Hazard Index (HI) analysis for heavy metals was found significantly high (>1) which is considered as a threat for human population because they have the tendency to accumulate in the body and cause variety of diseases like kidney problem, dysfunction of liver and renal cortex as well as cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Affective neuroscience of pleasure: reward in humans and animals

PubMed Central

2010-01-01

Introduction Pleasure and reward are generated by brain circuits that are largely shared between humans and other animals. Discussion Here, we survey some fundamental topics regarding pleasure mechanisms and explicitly compare humans and animals. Conclusion Topics surveyed include liking, wanting, and learning components of reward; brain coding versus brain causing of reward; subjective pleasure versus objective hedonic reactions; roles of orbitofrontal cortex and related cortex regions; subcortical hedonic hotspots for pleasure generation; reappraisals of dopamine and pleasure-electrode controversies; and the relation of pleasure to happiness. PMID:18311558

Task-specific reorganization of the auditory cortex in deaf humans

PubMed Central

Bola, Łukasz; Zimmermann, Maria; Mostowski, Piotr; Jednoróg, Katarzyna; Marchewka, Artur; Rutkowski, Paweł; Szwed, Marcin

2017-01-01

The principles that guide large-scale cortical reorganization remain unclear. In the blind, several visual regions preserve their task specificity; ventral visual areas, for example, become engaged in auditory and tactile object-recognition tasks. It remains open whether task-specific reorganization is unique to the visual cortex or, alternatively, whether this kind of plasticity is a general principle applying to other cortical areas. Auditory areas can become recruited for visual and tactile input in the deaf. Although nonhuman data suggest that this reorganization might be task specific, human evidence has been lacking. Here we enrolled 15 deaf and 15 hearing adults into an functional MRI experiment during which they discriminated between temporally complex sequences of stimuli (rhythms). Both deaf and hearing subjects performed the task visually, in the central visual field. In addition, hearing subjects performed the same task in the auditory modality. We found that the visual task robustly activated the auditory cortex in deaf subjects, peaking in the posterior–lateral part of high-level auditory areas. This activation pattern was strikingly similar to the pattern found in hearing subjects performing the auditory version of the task. Although performing the visual task in deaf subjects induced an increase in functional connectivity between the auditory cortex and the dorsal visual cortex, no such effect was found in hearing subjects. We conclude that in deaf humans the high-level auditory cortex switches its input modality from sound to vision but preserves its task-specific activation pattern independent of input modality. Task-specific reorganization thus might be a general principle that guides cortical plasticity in the brain. PMID:28069964

Task-specific reorganization of the auditory cortex in deaf humans.

PubMed

Bola, Łukasz; Zimmermann, Maria; Mostowski, Piotr; Jednoróg, Katarzyna; Marchewka, Artur; Rutkowski, Paweł; Szwed, Marcin

2017-01-24

The principles that guide large-scale cortical reorganization remain unclear. In the blind, several visual regions preserve their task specificity; ventral visual areas, for example, become engaged in auditory and tactile object-recognition tasks. It remains open whether task-specific reorganization is unique to the visual cortex or, alternatively, whether this kind of plasticity is a general principle applying to other cortical areas. Auditory areas can become recruited for visual and tactile input in the deaf. Although nonhuman data suggest that this reorganization might be task specific, human evidence has been lacking. Here we enrolled 15 deaf and 15 hearing adults into an functional MRI experiment during which they discriminated between temporally complex sequences of stimuli (rhythms). Both deaf and hearing subjects performed the task visually, in the central visual field. In addition, hearing subjects performed the same task in the auditory modality. We found that the visual task robustly activated the auditory cortex in deaf subjects, peaking in the posterior-lateral part of high-level auditory areas. This activation pattern was strikingly similar to the pattern found in hearing subjects performing the auditory version of the task. Although performing the visual task in deaf subjects induced an increase in functional connectivity between the auditory cortex and the dorsal visual cortex, no such effect was found in hearing subjects. We conclude that in deaf humans the high-level auditory cortex switches its input modality from sound to vision but preserves its task-specific activation pattern independent of input modality. Task-specific reorganization thus might be a general principle that guides cortical plasticity in the brain.

Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin.

PubMed

Oxlund, Christina; Kurt, Birgül; Schwarzensteiner, Ilona; Hansen, Mie R; Stæhr, Mette; Svenningsen, Per; Jacobsen, Ib A; Hansen, Pernille B; Thuesen, Anne D; Toft, Anja; Hinrichs, Gitte R; Bistrup, Claus; Jensen, Boye L

2017-06-01

The proteinase prostasin is a candidate mediator for aldosterone-driven proteolytic activation of the epithelial sodium channel (ENaC). It was hypothesized that the aldosterone-mineralocorticoid receptor (MR) pathway stimulates prostasin abundance in kidney and urine. Prostasin was measured in plasma and urine from type 2 diabetic patients with resistant hypertension (n = 112) randomized to spironolactone/placebo in a clinical trial. Prostasin protein level was assessed by immunoblotting in (1) human and rat urines with/without nephrotic syndrome, (2) human nephrectomy tissue, (3) urine and kidney from aldosterone synthase-deficient (AS -/- ) mice and ANGII- and aldosterone-infused mice, and in (4) kidney from adrenalectomized rats. Serum aldosterone concentration related to prostasin concentration in urine but not in plasma. Plasma prostasin concentration increased significantly after spironolactone compared to control. Urinary prostasin and albumin related directly and were reduced by spironolactone. In patients with nephrotic syndrome, urinary prostasin protein was elevated compared to controls. In rat nephrosis, proteinuria coincided with increased urinary prostasin, unchanged kidney tissue prostasin, and decreased plasma prostasin while plasma aldosterone was suppressed. Prostasin protein abundance in human nephrectomy tissue was similar across gender and ANGII inhibition regimens. Prostasin urine abundance was not different in AS -/- and aldosterone-infused mice. Prostasin kidney level was not different from control in adrenalectomized rats and AS -/- mice. We found no evidence for a direct relationship between mineralocorticoid receptor signaling and kidney and urine prostasin abundance. The reduction of urinary prostasin in spironolactone-treated patients is most likely the result of an improved glomerular filtration barrier function and generally reduced proteinuria.

Perspectives on using a multiplex human kidney safety biomarker panel to detect cisplatin-induced tubular toxicity in male and female Cynomolgus monkeys.

PubMed

Chen, Yafei; Dale Thurman, J; Kinter, Lewis B; Bialecki, Russell; Eric McDuffie, J

2017-12-01

Multiplex biomarker panel assays would enable early de-risking of discovery compound related kidney safety liabilities. The objective of this study was to evaluate the usefulness of the Myriad RBM Human KidneyMAP (Multi-Analyte Profile)® v.1.0 panel to detect experimental nephrotoxicity in Cynomolgus monkeys following a single intravenous administration of cisplatin (2.5mg/kg). Urine samples were collected at baseline on day -2; at approximately 4hr post-dose on day 1; and on days 4, 9, 15 and/or 20. Blood samples were collected at predose on day -2; at 4hr post-dose on day 1; and on days 2, 5, 10 and/or 21. Changes in toxicokinetic and biochemistry parameters in plasma, qualitative/quantitative urinalysis parameters, and urinary kidney safety biomarkers were assessed. Kidney tissues were collected on days 2, 5, 10 and 21 for routine microscopy. Cisplatin-induced tubular alterations were characterized by acute and progressive cortical tubular degeneration/necrosis, regeneration, tubular dilation and proteinaceous cast in the absence of statistically significant changes in traditional plasma biochemistry and urinalysis parameters. When normalized to urinary creatinine, cisplatin-induced significant increases in urinary levels of kidney injury molecule 1 (females on day 4), increases in calbindin D28k (males and females on day 4), decreases in Tamm-Horsfall glycoprotein (males on days 1, 4 and 9), and increases in clusterin (females and males on days 15 and 20, respectively), when compared to concurrent controls. This study revealed the usefulness of the Human KidneyMAP® multiplex panel when measuring changes in urine-based biomarkers to reliably detect cisplatin-induced acute/progressive cortical tubular injury in male and female Cynomolgus monkeys. Copyright © 2017 Elsevier Inc. All rights reserved.

Timing, timing, timing: Fast decoding of object information from intracranial field potentials in human visual cortex

PubMed Central

Liu, Hesheng; Agam, Yigal; Madsen, Joseph R.; Kreiman, Gabriel

2010-01-01

Summary The difficulty of visual recognition stems from the need to achieve high selectivity while maintaining robustness to object transformations within hundreds of milliseconds. Theories of visual recognition differ in whether the neuronal circuits invoke recurrent feedback connections or not. The timing of neurophysiological responses in visual cortex plays a key role in distinguishing between bottom-up and top-down theories. Here we quantified at millisecond resolution the amount of visual information conveyed by intracranial field potentials from 912 electrodes in 11 human subjects. We could decode object category information from human visual cortex in single trials as early as 100 ms post-stimulus. Decoding performance was robust to depth rotation and scale changes. The results suggest that physiological activity in the temporal lobe can account for key properties of visual recognition. The fast decoding in single trials is compatible with feed-forward theories and provides strong constraints for computational models of human vision. PMID:19409272

Functional organization of human intraparietal and frontal cortex for attending, looking, and pointing

NASA Technical Reports Server (NTRS)

Astafiev, Serguei V.; Shulman, Gordon L.; Stanley, Christine M.; Snyder, Abraham Z.; Van Essen, David C.; Corbetta, Maurizio

2003-01-01

We studied the functional organization of human posterior parietal and frontal cortex using functional magnetic resonance imaging (fMRI) to map preparatory signals for attending, looking, and pointing to a peripheral visual location. The human frontal eye field and two separate regions in the intraparietal sulcus were similarly recruited in all conditions, suggesting an attentional role that generalizes across response effectors. However, the preparation of a pointing movement selectively activated a different group of regions, suggesting a stronger role in motor planning. These regions were lateralized to the left hemisphere, activated by preparation of movements of either hand, and included the inferior and superior parietal lobule, precuneus, and posterior superior temporal sulcus, plus the dorsal premotor and anterior cingulate cortex anteriorly. Surface-based registration of macaque cortical areas onto the map of fMRI responses suggests a relatively good spatial correspondence between human and macaque parietal areas. In contrast, large interspecies differences were noted in the topography of frontal areas.